Use of physiological cooling ingredients and agents containing such active ingredients

0001The invention relates to novel modulators of the cold menthol receptor TRPM8, methods for modulating the TRPM8 receptor using these modulators; the use of the modulators to induce a feeling of cold; and the articles and means made using these modulators.

0002In a special aspect, the invention relates to an agent comprising at least one selected such modulator for achieving a cooling effect on the skin or mucous membrane, the cooling effect being longer compared to the known cooling agent menthan-3-carboxylic acid-N-ethylamide (WS3).

0003Furthermore, the special aspect of the invention relates to agents which comprise such selected TRPM8 receptor modulators, the agents serving for specific purposes. In addition, the special aspect of the invention relates to a method for achieving a physiological cooling effect on the skin or mucous membrane, in which the latter agents are used.

<u>Background of the Invention</u>

0004The cold menthol receptor TRPM8 (also called Cold-Membrane Receptor (CMR) 1) belongs to the family of "Transient Receptor Potential Ion Channels", is specifically expressed in a special group of neurons and forms pores in the cell membrane (each 4 units combine to form a tetramer), which selectively approx²⁺ Let ions pass. The protein has 6 transmembrane domains and a cytoplasmic C and N terminus. This receptor is stimulated by low temperatures (preferably 10-25 ° C), which leads to signal transduction, which the nervous system interprets as a feeling of cold. The receptor was first described as a cold receptor in several publications in 2002 (<nplcit id="ncit0001" npl-type="s"><text>Peier AM et al, .A TRP channel that senses cold stimuli and menthol.Cell. 2002 Mar 8; 108 (5): 705-15</text></nplcit>; <nplcit id="ncit0002" npl-type="s"><text>McKemy DD et al. Identification of a cold receptor reveals a general role for TRP channels in thermosensation Nature 2002 Mar 7; 416 (6876): 52-8</text></nplcit>;<nplcit id="ncit0003" npl-type="s"><text> Zuker CS. Neurobiology: A cool ion channel Nature 2002 Mar 7; 416 (6876): 27-8</text></nplcit>)

0005Cooling compounds, such as menthol, have long played an important role in the flavor and fragrance industry in order to create an association with freshness and cleanliness. The compound menthol has been shown to act as a natural modulator of the TRPM8 receptor (<nplcit id="ncit0004" npl-type="s"><text>McKemy DD, Molecular Pain 1, 2005, 16</text></nplcit>; <nplcit id="ncit0005" npl-type="s"><text>McKemy DD, Nature 416, 2002, 52-58</text></nplcit>;<nplcit id="ncit0006" npl-type="s"><text> Peier AM, Cell 108, 2002, 705-715</text></nplcit>; <nplcit id="ncit0007" npl-type="s"><text>Dhaka A., Annu. Rev. Neurosci. 29, 2006, 135-161</text></nplcit>). By application of menthol, TRPM8 is activated, whereby a Ca²⁺Influx into the cold-sensitive neurons is effected. The electrical signal generated by this is ultimately perceived as a feeling of cold. Excessive menthol concentrations lead to irritation and an anesthetic effect. In addition, menthol derivatives with a similar effect have been described in various publications (British patent<patcit id="pcit0001" dnum="GB1315761A"><text>1971 # 1315761</text></patcit><nplcit id="ncit0008" npl-type="s"><text>Watson HR, J. Soc. Cosmet. Chem. 29, 1978, 185-200</text></nplcit>; <nplcit id="ncit0009" npl-type="s"><text>Furrer SM, Chem. Percept. 1, 2008, 119-126</text></nplcit>). There are also isolated compounds structurally unrelated to menthol that produce significant TRPM8 modulation, such as: B. Icilin (<nplcit id="ncit0010" npl-type="s"><text>Wei ET, J. Pharm. Pharmacol. 35, 1983, 110-112</text></nplcit>; <patcit id="pcit0002" dnum="WO2004026840A"><text>WO 2004/026840</text></patcit>), WS-23 or in the patent application <patcit id="pcit0003" dnum="WO2007019719A"><text>WO 2007/019719</text></patcit> listed connections.

0006Other effects of substances that modulate the TRPM8 receptor or its insect analogues are a repellent effect on insects (<patcit id="pcit0004" dnum="WO2002015692A"><text>WO 2002/015692</text></patcit>; <patcit id="pcit0005" dnum="WO2004000023A"><text>WO 2004/000023</text></patcit>, <patcit id="pcit0006" dnum="US20040028714A"><text>US 2004/0028714</text></patcit>), as well as activity in antitumor therapy (e.g. influencing prostate tumors), activity in the treatment of inflammatory pain / hyperalgesia and an effect as TRPM8 antagonists in the therapy of bladder syndrome or overactive bladder (<nplcit id="ncit0011" npl-type="s"><text>Beck B. Cell Calcium, 41, 2007, 285-294</text></nplcit>; <nplcit id="ncit0012" npl-type="s"><text>Levine JD Biochim. Biophys. Acta, Mol. Basis Dis. 1772, 2007, 989-1003</text></nplcit>; <nplcit id="ncit0013" npl-type="s"><text>Mukerji G., BMC Urology 6, 2006, 6</text></nplcit>; <patcit id="pcit0007" dnum="US20030207904A"><text>US 2003/0207904</text></patcit>; <patcit id="pcit0008" dnum="US20056893626A"><text>US 2005/6893626</text></patcit>, Dissertation Behrendt HJ 2004, University of Bochum; <nplcit id="ncit0014" npl-type="s"><text>Lashinger ESR Am. J. Physiol. Renal Physiol. At the J Physiol Renal Physiol. 2008 Jun 18</text></nplcit>. [Epub ahead of print]; PMID: 18562636).

0007However, many of the TRPM8 modulators found to date have deficiencies in terms of potency, duration of action, skin / mucous membrane irritation, odor, taste, solubility and / or volatility.

0008In the older international patent application<patcit id="pcit0009" dnum="EP2009061019W"><text> PCT / EP2009 / 061019</text></patcit> Applicant's filing date August 26, 2009, individual compounds for modulating the TRPM8 receptor are proposed. These are the following, specifically disclosed connections:<chemistry id="chem0001" num="0001"><img file="EP3663366A2_D0001.tif" /></chemistry><chemistry id="chem0002" num="0002"><img file="EP3663366A2_D0002.tif" /></chemistry>wherein the compound can be in chemically pure or enriched form, as a single stereoisomer or in the form of stereoisomer mixtures.

0009These connections are known per se:<ul id="ul0001" list-style="none" compact="compact"><li>Connection 1 under <nplcit id="ncit0015" npl-type="c"><text>CAS number: 99602-94-5 </text></nplcit>(3R cis shape)</li><li>Connection 2 under <nplcit id="ncit0016" npl-type="c"><text>CAS number: 165753-08-2 </text></nplcit></li><li>Connection 3 under<nplcit id="ncit0017" npl-type="c"><text> CAS number: 338771-57-6 </text></nplcit></li><li>Connection 4 under <nplcit id="ncit0018" npl-type="c"><text>CAS number: 878942-21-3 </text></nplcit></li><li>Connection 5 under <nplcit id="ncit0019" npl-type="c"><text>CAS number: 748783-13-3</text></nplcit> (without stereochemistry)</li></ul>

0010This specifically disclosed use of compounds 1 to 5 of <patcit id="pcit0010" dnum="EP2009061019W"><text>PCT / EP2009 / 061019</text></patcit> is explicitly excluded from the present registration.

0011It can also be found in the <patcit id="pcit0011" dnum="EP2009061019W"><text>PCT / EP2009 / 061019</text></patcit> the generic disclosure that the compounds described there may optionally be uncharged or in the form of their salts, such as, for example, as an acid addition salt. However, no such salts are specifically disclosed.

0012It can also be found in the <patcit id="pcit0012" dnum="EP2009061019W"><text>PCT / EP2009 / 061019</text></patcit> the generic disclosure that functional groups which may be present in the compounds described there may optionally be replaced by equivalent chemical groups; for example, oxygen groups (such as ether groups) can be replaced by corresponding sulfur groups and vice versa; Keto groups can be replaced by corresponding thionyl groups. However, no such modifications have been specifically disclosed.

0013The disclosure of this international patent application <patcit id="pcit0013" dnum="EP2009061019W"><text>PCT / EP2009 / 061019</text></patcit> is hereby explicitly deemed to be excluded from the scope of the present invention insofar as it is necessary to differentiate it.

<u>Summary of the main invention (general part)</u>

0014The object of the present invention was therefore to identify new substances which lead to a modulation of the TRPM8 receptor, which can be used as alternatives to the previously known modulators. Such compounds should in particular also be used for cosmetics (e.g. hair care, skin care, oral care), nutrition (feed / food), textiles, OTC products (e.g. burn ointment), pharmaceuticals (e.g. tumor treatment, bladder weakness) or packaging.

<u>Figure description (general part):</u>

0015<ul id="ul0002" list-style="none"><li><figref idref="f0001 f0002">Figure 1</figref> shows (a) the mRNA sequence (SEQ ID NO: 1) or (b) the amino acid sequence derived therefrom (SEQ ID NO: 2) of the hTRPM8 receptor according to the sequence database entry <u>NM 024080.</u></li><li><figref idref="f0003">Figure 2</figref> shows the vector map of the plasmid plnd_M8 coding for hTRPM8, which was used for the transfection of the HEK293 cells.</li></ul>

<u>Detailed description of the invention:</u>

1. Definitions

1.1 General terms

0016In the literature there are various synonyms for "TRPM8": TRPP8, LTRPC6, CMR1, MGC2849, transient receptor potential cation channel subfamily M member 8. In the sense of the present invention, all terms are included. Also included are all functional modifications of the receptor, such as in particular splice variants, isoforms, such as, for example, TRPM8 CRA_a, TRPM8 CRA_b and all analogue receptors from different organisms, such as humans, mice, rats. The nucleotide or Amino acid sequences of the different receptors are known per se and stored in sequence databases. For example, the sequence information for hTRPM8 is entered under number NM_024080.

0017A "modulator" in the sense of the invention represents a compound that acts as an agonist and / or antagonist of the TRPM8 receptor <i>in vivo</i> and or <i>in vitro,</i> in particular <i>in vivo</i> can work.

0018Suitable modulators can either act only as an antagonist or agonist, in particular only as an agonist, or both as an antagonist and as an agonist. In particular, an agonistic or an antagonistic effect can occur depending on the particular modulator concentration selected.

0019An "agonist" is a compound that mediates activation of the TRPM8 receptor, ie a Ca²⁺ -Influx induced in the cold-sensitive neurons and thus gives a feeling of cold. An "antagonist", on the other hand, is a compound that can counteract this activation of the TRPM8 receptor.

0020The mediators according to the invention can exert their action by reversibly or irreversibly, specifically or nonspecifically binding to a TRPM8 receptor molecule. Usually the binding takes place non-covalently via ionic and / or nonionic, such as hydrophobic, interactions with the receptor molecule. "Specific" includes both exclusive interaction with one or more different TRPM8 receptor molecules (such as TRPM8 molecules of different origins or different isoforms). "Nonspecific", on the other hand, is an interaction of the modulator with several different receptor molecules with different functions and / or sequences, whereby however a desired agonistic and / or antagonistic modulation (as described above) of the TRPM8 receptor can be determined.

0021In this context, “standard conditions” in a cellular activity test for modulators according to the invention mean an activity test carried out with HEK293 cells which have been transformed with human TRPM8 and are loaded with calcium-sensitive dye (such as, for example, Fluo-4AM, ie Fluo-4 Acetoxymethyl ester), then adding the test compound and detecting the color change, the experiment being carried out at 37 ° C .; such as described in reference example 3, below, or in Behrendt et al (2004) loc. cit.).

0022A "modified form" or "derivative" of a modulator according to the invention is also referred to as a "functional analog" or "functionally equivalent compound", especially if it continues to show the desired biological activity (receptor TRPM8 modulation). "Derivatives" in the sense of the invention are also compounds which allow coupling of the specifically disclosed substances to solid carriers; a large selection of corresponding linker / spacer groups is known to the person skilled in the art. The derivatization can take place before the coupling to a solid phase or only through the coupling.

0023A modulator according to the invention is used in particular to induce a feeling of cold, in humans and / or animals. An "induction of feeling cold" is present when the compound shows an agonistic effect on hTRPM8 in the cellular activity test described above. Agents according to the invention contain, in addition to the constituents customary for the respective agent, an effective amount of at least one modulator according to the invention. "Effective" in this context means a concentration of the modulator which is sufficient to impart the desired effect, such as pharmacological effect, or sensory effect such as the olfactory cold effect when the agent is applied (for example application to the skin).

0024A "topical" application includes, in particular, cutane or oral forms of use.

1.2 Chemical terms

0025If no other information is given, the following general meanings apply within the scope of the present invention:<ul id="ul0003" list-style="none"><li><b>Halogen:</b> F, Cl, Br or J</li><li><b>Alkyl and all alkyl parts in residues derived therefrom, such as. Alkoxy, alkylthio, alkoxyalkyl, alkoxyalkoxy, alkylamino and dialkylamino:</b> saturated, straight-chain or branched hydrocarbon radicals having 1 to 4, 1 to 6, 1 to 8, 1 to 10 or 1 to 10 carbon atoms, e.g. B.<ul id="ul0004" list-style="dash" compact="compact"><li><b>C.₁-C₆-Alkyl</b> such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl , 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3 -Dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.</li><li><b>C.₁-C₆-Alkoxy,</b> full <b>C.₁-C₄-Alkoxy,</b> such as methoxy, ethoxy, n-propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy; and z. B. Pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1, 1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy;</li></ul><b>Alkenyl:</b> one or more, in particular monounsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4, 2 to 6, 2 to 8, 2 to 10 or 2 or to 20 carbon atoms and a double bond in any position, for. B. C₂-C₆Alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2 propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl , 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1 , 1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1- Methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4- pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2- methyl 2-propenyl;</li><li><b>Halo (gen) alkyl:</b> straight-chain or branched alkyl groups having 1 to 4, 1 to 6, 1 to 8, 1 to 10 or 1 to 20 carbon atoms (as mentioned above), in which groups the hydrogen atoms can be partially or completely replaced by halogen atoms as mentioned above, e.g. . B. C₁-C₂Haloalkyl such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2 Trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and 1,1,1-trifluoroprop-2 -yl.</li><li><b>Halogenalkoxy:</b> for an alkoxy radical having 1 to 8, in particular 1 to 6 and especially 1 to 4 carbon atoms as mentioned above, which is partially or completely substituted by fluorine, chlorine, bromine and / or iodine, preferably by fluorine, that is, for. B. OCH₂F, OCHF₂, OCF₃, OCH₂Cl, OCHCl₂, OCCl₃, Chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2 , 2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, OC₂F₅, 2-fluoropropoxy, 3-fluoropropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3-bromopropoxy, 3,3,3-trifluoropropoxy , 3,3,3-trichloropropoxy, OCH₂-C₂F₅, OCF₂-C₂F₅, 1- (CH₂F) -2-fluoroethoxy, 1- (CH₂Cl) -2-chloroethoxy, 1- (CH₂Br) -2-bromethoxy, 4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy or nonafluorobutoxy;</li><li><b>Cycloalkyl:</b> carbocyclic radicals with 3 to 20 carbon atoms, such as C₃-C₁₂Cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl and cyclododecyl; cyclopentyl, cyclohexyl, cycloheptyl, and cyclopropyl-methyl, cyclopropyl-ethyl, cyclobutyl-methyl, cyclobutyl-ethyl, cyclopentyl-methyl, cyclopentyl-ethyl, cyclohexyl-methyl or C are preferred₃-C₇-Cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropyl-methyl, cyclopropyl-ethyl, cyclobutyl-methyl, cyclopentyl-ethyl, cyclohexyl-methyl, the linkage to the rest of the molecule being possible via any suitable carbon atom .</li><li><b>Cycloalkenyl:</b> monocyclic, monounsaturated hydrocarbon groups with 5 to 8, preferably up to 6 carbon ring members, such as cyclopenten-1-yl, cyclopenten-3-yl, cyclohexen-1-yl, cyclohexen-3-yl and cyclohexen-4-yl;</li><li><b>Alkylene:</b> straight-chain or single or multiple branched hydrocarbon bridge groups with 1 to 20 carbon atoms, such as C₁-C_7-Alkylene groups selected from -CH₂-, - (CH₂)₂-, - (CH2) 3 -, - (CH2) 4-, - (CH2) 2-CH (CH3) -, -CH2-CH (CH3) -CH2-, (CH2) 4-, - (CH2) 5 -, - (CH2) 6, - (CH2) 7-, - CH (CH₃) -CH₂-CH₂-CH (CH₃) - or -CH (CH₃) -CH₂-CH₂-CH₂-CH (CH₃) - or C₁-C₄-Alkylene groups selected from -CH2-, - (CH2) 2-, - (CH2) 3 -, - (CH2) 4-, - (CH2) 2-CH (CH3) -, -CH2-CH (CH3) -CH2 -.</li><li><b>Alkenylene:</b> the mono- or polysaturated, in particular monounsaturated, analogs of the above alkylene groups with 2 to 20 carbon atoms, especially for C₂-C₇-Alkenylene or C.₂-C₄-Alkenylene, such as -CH = CH-, -CH = CH-CH₂-, - CH₂-CH = CH-, -CH = CH-CH₂-CH₂-, -CH₂-CH = CH-CH₂-, -CH₂-CH₂-CH = CH-, -CH (CH₃) -CH = CH-, -CH₂-C (CH₃) = CH-,</li><li><b>Aryl:</b> mono- or polynuclear, preferably mono- or dinuclear, optionally substituted aromatic radicals having 6 to 20 such as 6 to 10 ring carbon atoms such as phenyl, biphenyl, naphthyl such as 1- or 2-naphthyl, tetrahydronaphthyl, fluorenyl, indenyl and phenanthrenyl. These aryl radicals can optionally carry 1, 2, 3, 4, 5 or 6 identical or different substituents.</li><li><b>Arylalkyl:</b> the aryl-substituted analogs of the above alkyl radicals, where aryl also has the meanings given above, such as phenyl-C₁-C₄Alkyl residues selected from phenyl-methyl or phenyl-ethyl.</li><li><b>Aryloxy:</b> the oxygen-linked analogs of the above optionally substituted aryl radicals.</li><li><b>Heterocyclyl:</b> five- to seven-membered saturated, partially unsaturated or aromatic heterocycles or heterocyclyl radicals containing one, two, three or four heteroatoms from the group O, N or S. For example, the following subgroups can be mentioned<ul id="ul0005" list-style="dash"><li>5- or 6-membered saturated or monounsaturated heterocyclyl, containing one to two nitrogen atoms and / or one oxygen or sulfur atom or one or two oxygen and / or sulfur atoms as ring members, e.g. B. 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl Isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 2-pyrroline 2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1,3-dioxan-5-yl, 2-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, 3-hexahydropyridazinyl, 4-hexahydropyridazinyl, 2-hexahydiminyl 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl and 2-piperazinyl;</li><li>5-membered aromatic heterocyclyl (= <b>Heteroaryl</b> respectively. <b>Hetaryl),</b> containing in addition to carbon atoms one, two or three nitrogen atoms or one or two nitrogen atoms and a sulfur or oxygen atom as ring members, for. B. 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, and 1,3,4-triazol-2-yl;</li><li>5-membered aromatic heterocyclyl (= <b>Heteroaryl</b> respectively. <b>Hetaryl),</b> which has 1, 2, 3 or 4 nitrogen atoms as ring members, such as 1-, 2- or 3-pyrrolyl, 1-, 3- or 4-pyrazolyl, 1-, 2- or 4-imidazolyl, 1,2,3- [1H] triazol-1-yl, 1,2,3- [2H] triazol-2-yl, 1,2,3- [1H] triazol-4-yl, 1,2,3- [1H ] Triazol-5-yl, 1,2,3- [2H] triazol-4-yl, 1,2,4- [1H] triazol-1-yl, 1,2,4- [1H] - Triazol-3-yl, 1,2,4- [1H] triazol-5-yl, 1,2,4- [4H] triazol-4-yl, 1,2,4- [4H] triazol- 3-yl, [1H] tetrazol-1-yl, [1H] tetrazol-5-yl, [2H] tetrazol-2-yl and [2H] tetrazol-5-yl;</li><li>5-membered aromatic heterocyclyl (= <b>Heteroaryl</b> respectively. <b>Hetaryl),</b> the 1 hetero atom selected from oxygen and sulfur and optionally 1, 2 or 3 nitrogen atoms as ring members, for example 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 3- or 4-isoxazolyl, 3- or 4-isothiazolyl , 2-, 4- or 5-oxazolyl, 2-, 4 or 5-thiazolyl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4- Thiadiazol-2-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl and 1,3,4-oxadiazol-2-yl;</li><li>6-membered heterocyclyl (= <b>Heteroaryl</b> respectively. <b>Hetaryl),</b> containing in addition to carbon atoms one or two or one, two or three nitrogen atoms as ring members, for. B. 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,2,4-triazin-3-yl; 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl and 1,3,5-triazin-2-yl;</li></ul></li><li><b>Heteroaryloxy</b> respectively.<b>Heteroaryloxy</b> stands for the oxygen-linked analogs of the above heterocyclyl or heteroaryl residues.</li><li><b>Substituents,</b> as in particular for the above radicals, are in particular selected from keto groups, - COOH, -COO-alkyl, -OH, -SH, -CN, amino, -NO₂, Alkyl, or alkenyl groups, where one or more H atoms in the alkyl or alkenyl groups can be replaced by halogen.</li></ul>

0026The definitions given in this chapter also apply to the special aspect of the invention (see chapter 6) unless stated otherwise.

<u>2nd Special embodiments of the invention (general part):</u>

0027The invention particularly relates to the following special embodiments: 1. Method for the in vitro or in vivo modulation of the cold menthol receptor TRPM8, wherein the receptor is brought into contact with at least one modulator which is selected from compounds of the following structure types 1 to 3: a) Structure type 1:<chemistry id="chem0003" num="0003"><img file="EP3663366A2_D0003.tif" /></chemistry>wherein<ul id="ul0006" list-style="none"><li>R₁₁, R₁₂ and R₁₃ are independently selected from:<ul id="ul0007" list-style="none" compact="compact"><li>H; straight-chain or branched C₁-C₆-Alkylgruppen, which optionally carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; and</li><li>straight-chain or branched C₁-C₆-Alkyloxy groups, which optionally carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or</li><li>R₁₁ and R₁₂ together with the carbon atoms to which they are attached form a 4-, 5-, 6- or 7-membered, mono- or polyunsaturated, carbo- or heterocyclic ring which may be 1, 2, 3, 4 or 5 identical or carries various substituents which are selected from straight-chain or branched C₁-C₆-Alkyl groups, and oxo groups (= O), and the ring heteroatoms are the same or different and are selected from O, N and S;</li></ul></li><li>X and Z are independently selected from -O-, -S-, -NH-, -S (= O) -, or-S (= O)₂- Groups; and</li><li>Y is selected under straight-chain or branched C₁-C₈Alkylene groups, which may carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or</li><li>XYZ together with the carbon atom to which they are attached form a keto group,</li><li>and salts of these compounds, in particular acid addition salts with inorganic or in particular organic, mono- or in particular polyvalent carboxylic acids;</li><li>optionally in stereoisomerically pure form or as a mixture of stereoisomers;</li><li>and where appropriate the connections with the structure<chemistry id="chem0004" num="0004"><img file="EP3663366A2_D0004.tif" /></chemistry>and<chemistry id="chem0005" num="0005"><img file="EP3663366A2_D0005.tif" /></chemistry>with exception of;</li></ul>b) Structure type 2:<chemistry id="chem0006" num="0006"><img file="EP3663366A2_D0006.tif" /></chemistry>wherein<ul id="ul0008" list-style="none"><li>R₂₁ and R₂₂ are independently selected from:<ul id="ul0009" list-style="none" compact="compact"><li>H;</li><li>straight-chain or branched C₁-C₆-Alkylgruppen, which optionally carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>straight-chain or branched C₁-C₆-Alkyloxy groups, which may carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>mononuclear or polynuclear aryl, arylalkyl and heteroaryl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S;</li></ul></li><li>R23 is selected from:<ul id="ul0010" list-style="none" compact="compact"><li>H;</li><li>straight-chain or branched C₁-C₆-Alkyl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>C.₃-C₇-Cycloalkyl groups, which may have 1,2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups, or straight-chain or branched C₁-C₆-Alkoxy groups; where the cycloalkyl group optionally via a C₁-C₄-Alkylene group is bonded to Z; and where optionally 1, 2 or 3 ring carbon atoms can be replaced by identical or different heteroatoms selected from O, N and S;</li><li>mononuclear or polynuclear aryl, arylalkyl and heteroaryl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S;</li><li>X is selected from O, S or methylene;</li></ul></li><li>Y is selected from N or CH; and</li><li>Z is selected from O, S or NR₂₄ , in which<ul id="ul0011" list-style="none" compact="compact"><li>R₂₄ for H; or a straight-chain or branched C₁-C₆-Alkylgruppe, which optionally carries 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or</li><li>R₂₄ and R₂₃ together with the Z group to which they are attached form a 4-, 5-, 6- or 7-membered, saturated or mono- or polyunsaturated heterocyclic ring which may be 1, 2, 3, 4 or 5 carries the same or different substituents, which are selected from straight-chain or branched C₁-C₆Alkyl groups, and which has 1, 2 or 3 additional ring heteroatoms which are the same or different and are selected from O, N and S;</li></ul></li><li>and salts of these compounds, in particular acid addition salts with inorganic or in particular organic, mono- or in particular polyvalent carboxylic acids;</li><li>optionally in stereoisomerically pure form or as a mixture of stereoisomers;</li><li>and where appropriate the connection to the structure<chemistry id="chem0007" num="0007"><img file="EP3663366A2_D0007.tif" /></chemistry>is excluded; and</li></ul>c) Structure type 3:<chemistry id="chem0008" num="0008"><img file="EP3663366A2_D0008.tif" /></chemistry>wherein R₃₁, R₃₂, R₃₃, R₃₄ and R₃₅ are the same or different and are selected from<ul id="ul0012" list-style="none" compact="compact"><li>H;</li><li>Halogen;</li><li>straight-chain or branched C₁-C₆-Alkyl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>straight-chain or branched C₁-C₆Alkoxy groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or C₁-C₆-Alkoxy groups;</li><li>mononuclear or polynuclear aryl, arylalkyl and heteroaryl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S; or</li></ul>two adjacent residues R₃₁, R₃₂, R₃₃, R₃₄ and R₃₅ together with the carbon atoms to which they are attached form a 4-, 5-, 6- or 7-membered, mono- or polyunsaturated heterocyclic ring which may have 1, 2, 3, 4 or 5 identical or different substituents , which are selected from straight-chain or branched C₁-C₆Alkyl groups, and which has 1, 2 or 3 ring heteroatoms which are the same or different and are selected from O, N and S; R₃₆ and R₃₇ are the same or different and are selected from:<ul id="ul0013" list-style="none" compact="compact"><li>straight-chain or branched C₁-C₆-Alkyl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>mononuclear or polynuclear aryl, arylalkyl, aryloxy, heteroaryl and heteroaryloxy groups which may carry 1, 2, 3 or 4 identical or different substituents selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups;</li><li>wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S;</li><li>and C₃-C₇-Cycloalkyl groups, which may have 1,2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups, or straight-chain or branched C₁-C₆-Alkoxy groups; where the cycloalkyl group optionally via a C₁-C₄-Alkylene group is bound; and where optionally 1, 2 or 3 ring carbon atoms can be replaced by identical or different heteroatoms selected from O, N and S;</li></ul>X is selected under -C₁-C₄Alkylene groups; -C₂-C₄-Alkenylene groups, and -ZC₁-C₄- or -C₁-C₄-Z-alkylene groups or -ZC₂-C₄- or - C₂-C₄-Z-alkenylene groups, where Z is O, S or NH; or represents a chemical single bond; and salts of these compounds, in particular acid addition salts with inorganic or in particular organic, mono- or in particular polyvalent carboxylic acids; optionally in stereoisomerically pure form or as a mixture of stereoisomers; and where appropriate the connections with the structure<chemistry id="chem0009" num="0009"><img file="EP3663366A2_D0009.tif" /></chemistry>and<chemistry id="chem0010" num="0010"><img file="EP3663366A2_D0010.tif" /></chemistry>with exception of. and preferably selected from the more specific groups of structure types 1, 2 and 3 listed below; in particular those compounds of the above formulas which, in a cellular activity test, in particular under standard conditions, using cells which recombinantly express the human TRPM8 receptor, determine the permeability of these cells for Ca²⁺ Modulate ions; or in particular those compounds that target the cellular Ca²⁺Ion permeability act a-gonistically or antagonistically, where in each case the respective compounds of Table V<tables id="tabl0001" num="0001"><table frame="all"><title>(Table V)</title><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="12mm" /><colspec colnum="2" colname="col2" colwidth="57mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">2</entry><entry valign="middle"><chemistry id="chem0011" num="0011"><img file="EP3663366A2_D0011.tif" /></chemistry></entry></row><row><entry valign="middle">5</entry><entry valign="middle"><chemistry id="chem0012" num="0012"><img file="EP3663366A2_D0012.tif" /></chemistry></entry></row><row><entry valign="middle">9</entry><entry valign="middle"><chemistry id="chem0013" num="0013"><img file="EP3663366A2_D0013.tif" /></chemistry></entry></row><row><entry valign="middle">23</entry><entry valign="middle"><chemistry id="chem0014" num="0014"><img file="EP3663366A2_D0014.tif" /></chemistry></entry></row><row><entry valign="middle">31</entry><entry valign="middle"><chemistry id="chem0015" num="0015"><img file="EP3663366A2_D0015.tif" /></chemistry></entry></row></tbody></tgroup></table></tables>with exception of. 2. Use of a compound as defined for one of the structure types of embodiment 1, for inducing a feeling of cold in humans and / or animals, if appropriate for non-therapeutic purposes. 3. Use of a compound as defined in embodiment 1 as an active ingredient of a pharmaceutical agent. 4th Use of a compound as defined in embodiment 1, for the treatment of prostate cancer, for the treatment of bladder weakness or in pain therapy. 5. Use of a compound as defined in embodiment 1 for inducing a feeling of cold in a packaging, for example made of paper or plastic in various processing forms (such as Fibers, fabrics, molded parts), whereby the feeling of cold is particularly noticeable when it comes into contact with the packaging material. The substances can be associated with the packaging material in a wide variety of ways: e.g. by spin coating, printing, in the form of microencapsulation, direct incorporation into the packaging material (e.g. extrude), covalent coupling of suitable derivatives of the modulators (via suitable spacer / linker groups, with the aid of which the molecule is bound reversibly or irreversibly to the packaging material). Suitable procedures are known to the person skilled in the art. 6. Use of a compound as defined in embodiment 1 to induce a feeling of cold in a textile. The substances can be associated with the textile in various ways: for example by spin coating, printing, in the form of microencapsulation, direct incorporation into the textile material (e.g. extrusion), covalent coupling of suitable derivatives of the modulators (via suitable spacer / linker groups, with the aid of which the molecule is reversibly or irreversibly bound to the packaging material) . Suitable procedures are known to the person skilled in the art. 7. Substance as defined in embodiment 1 for use as a mediator of the TRPM8 receptor and in particular as an agonist thereof, and above all for inducing a feeling of cold in humans and / or animals. Due to an expanded property profile of compounds according to the invention, their use can serve several purposes simultaneously. For example, compounds of structure type 3 are suitable as UV absorbers, so that, for example a combined use of this compound as a UV absorber and cooling agent, for example in sun creams, is particularly advantageous. 8. Means containing at least one compound according to embodiment 1. 9. Means according to embodiment 8, selected from<ol id="ol0001" compact="compact"><li>a) pharmaceutical agents, such as anti-tumor agents, agents for the treatment of diseases of the bladder, pain relievers;</li><li>b) foods, such as ice cream, mousse, cream, beverages, confectionery;</li><li>c) oral care products such as toothpaste, mouthwash, chewing gum; Breath freshener</li><li>d) body care products, such as skin or hair care products, such as sunscreen, sunburn cream, lotions, shampoos, shaving cream, conditioners, facial cleansers, soaps, bath oils and bath foams, antiperspirants, deodorants,</li><li>e) foams and gels.</li></ol>10. Product containing at least one compound according to embodiment 1, selected from<ol id="ol0002" compact="compact"><li>a) textile products, such as shirts, pants, socks, towels,</li><li>b) packaging materials,</li><li>c) tobacco products;</li><li>d) remedies (plasters, dressing materials)</li><li>e) hygiene products (sponges, diapers, panty liners, cleaning cloths)</li><li>f) refreshing towels</li></ol>11. Compounds as defined in embodiment 1. 12. Compounds according to embodiment 1, selected from the compounds of the formulas 1-1 to 1-9, 2-1 to 2-22 and 3-1 to 3-49 listed in Tables A, B and C (below), optionally in stereoisomerically pure form, as a mixture of stereoisomers, and salts of these compounds.

0028In all of the embodiments according to the invention, the compounds of Table V above may optionally be excluded. This applies in particular to the configurations described in the following chapter.

0029The embodiments described in this chapter are further specified, inter alia, in chapter 6 (special aspect of the invention).

3rd Further refinements of the methods, uses and active substances according to the invention:

0030The following special configurations of active substances according to the invention apply mutatis mutandis both to the active substances per se and to their applications according to the invention, for example in the agents, processes and uses claimed according to the invention.

3.1 Compounds of formula I (structure type 1):

0031<chemistry id="chem0016" num="0016"><img file="EP3663366A2_D0016.tif" /></chemistry>selected from compounds of the following groups (1) to (18):<ol id="ol0003"><li>(1) Compounds of formula I, wherein R₁₃ for H, straight-chain or branched C₁-C₆Alkyl groups, in particular H;</li><li>(2) Compounds of formula I, wherein R₁₁ and R₁₂ together with the carbon atoms to which they are attached, form a 5- or 6-membered, monounsaturated carbo- or heterocyclic ring which optionally bears 1, 2 or 3 identical or different substituents which are selected from straight-chain or branched C₁-C₆-Alkyl groups, and oxo groups (= O); and the ring heteroatoms are O atoms;</li><li>(3) Compounds of formula I, wherein R₁₁ and R₁₂ together with the carbon atoms to which they are attached, form a 5- or 6-membered, monounsaturated, carbo- or heterocyclic ring which may have 1, 2 or 3 identical or different substituents selected from straight-chain C₁-C₄-Alkyl groups and one oxo group (= O); and the ring hetero atom is an O atom;</li><li>(4) Compounds of formula I, wherein R₁₁ and R₁₂ together form bridging groups, selected under<ul id="ul0014" list-style="none" compact="compact"><li>-C (= O) -OC * H (CH₃) - in both stereoisomeric forms</li><li>-C (= O) -CH₂-C (CH₃)₂-CH₂-</li><li>-C (= O) -CH₂-CH₂-CH₂-</li></ul>the keto group via the R12 or in particular via the R₁₁Position is bound to the molecule.</li><li>(5) Compounds of the formula I in which X and Z are identical or different and are selected from -S-, -S (= O) -, or -S (= O)₂- Groups;</li><li>(6) compounds of the formula I in which X and Z are identical and each represent -S-;</li><li>(7) Compounds of the formula I in which X and Z are different and are selected -S (= O) -, or -S (= O)₂- Groups;</li><li>(8) Compounds of the formula I in which Y is selected from straight-chain C₂- or C₃-Alkylene groups, especially -CH₂-CH₂- or -CH₂-CH₂-CH₂- ,</li><li>(9) Compounds of formula I, wherein XYZ together with the carbon atom to which they are attached form a keto group;</li><li>(10) Combinations of the embodiments: (1) + (2), (1) + (3), (1) + (4)</li><li>(11) Combinations of the embodiments: (1) + (5), (1) + (6), (1) + (7)</li><li>(12) combinations of the embodiments: (1) + (8),</li><li>(13) combinations of the embodiments: (1) + (9),</li><li>(14) Combinations of the embodiments: (10) + (5), (10) + (6), (10) + (7)</li><li>(15) Combinations of the embodiments: (10) + (8)</li><li>(16) Combinations of the embodiments: (10) + (9)</li><li>(17) Combinations of the embodiments: (14) + (8)</li><li>(18) combinations of the embodiments: (11) + (8)</li></ol>

3.2 Compounds of Formula II (Structure Type 2):

0032<chemistry id="chem0017" num="0017"><img file="EP3663366A2_D0017.tif" /></chemistry>selected from compounds in the following groups (1) to (61):<ol id="ol0004"><li>(1) Compounds of formula II, wherein X is O;</li><li>(2) Compounds of Formula II, wherein X is methylene;</li><li>(3) Compounds of Formula II, wherein Z is O;</li><li>(4) Compounds of formula II, wherein Z is NH;</li><li>(5) Compounds of formula II, wherein Y is N;</li><li>(6) compounds of formula II, wherein Y is CH;</li><li>(7) Compounds of formula II, wherein R₂₁ for a straight-chain or branched C₁-C₆-Alkyl group; or stands for a mononuclear aryl, arylalkyl and heteroaryl group, the heteroaryl group having 1 or 2 ring heteroatoms which are identical or different and are selected from O, N and S;</li><li>(8) Compounds of formula II, wherein R₂₁ for a straight-chain or branched C₁-C₆Alkyl group, or a mononuclear aryl group,</li><li>(9) Compounds of formula II, wherein R₂₁ represents methyl, ethyl, n-propyl, i-propyl, n-butyl, sec. butyl, i-buty, tert-butyl or phenyl, in particular methyl;</li><li>(10) Compounds of formula II, wherein R₂₂ for H, a straight-chain or branched C₁-C₆-Alkyl group; or stands for a mononuclear aryl, arylalkyl and heteroaryl group, the heteroaryl group having 1 or 2 ring heteroatoms which are identical or different and are selected from O, N and S;</li><li>(11) Compounds of formula II, wherein R₂₂ for H, a straight-chain or branched C₁-C₆Alkyl group,</li><li>(12) Compounds of formula II, wherein R₂₂ represents H, methyl, ethyl, n-propyl, i-propyl, n-butyl, sec. butyl, i-buty, tert-butyl or phenyl, in particular H;</li><li>(13) Compounds of formula II, wherein R₂₃ selected is straight-chain or branched C₁-C₆-Alkyl groups which may carry 1 or 2 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; C.₃-C₇-Cycloalkyl groups, the cycloalkyl group optionally via a C₁-C₄Alkylene group is bonded to Z, and optionally 1, 2 or 3 ring carbon atoms can be replaced by identical or different heteroatoms selected from O, N and S; mononuclear aryl, arylalkyl and heteroaryl groups, the heteroaryl groups having 1 or 2 ring heteroatoms which are the same or different and are selected from O, N and S;</li><li>(14) Compounds of formula II, wherein R₂₃ is selected from straight-chain or branched C₁-C₆-Alkylgruppen, which optionally carry 1 substituent, which is selected from OH, or straight-chain or branched C₁-C₃-Alkoxy groups; C.₃-C₇-Cycloalkyl groups, the cycloalkyl group optionally via a C₁-C₄Alkylene group is bonded to Z, and optionally 1 or 2 ring carbon atoms can be replaced by identical or different heteroatoms selected from O and N;</li><li>(15) Compounds of the formula II, in which R₂₃ is selected from:<ul id="ul0015" list-style="none" compact="compact"><li>Methyl, ethyl, n-propyl, i-propyl, n-butyl, sec.-butyl, i-butyl, tert-butyl, n-pentyl (amyl), 2-pentyl (sec-pentyl), 3-pentyl, 2 -Methylbutyl, 3-methylbutyl (iso-pentyl or iso-amyl), 3-methylbut-2-yl, 2-methylbut-2-yl; 2,2-dimethylpropyl (neopentyl);</li><li>1-methoxy-prop-2-yl; 1-methoxy-prop-3yl, 1-hydroxy-prop-2-yl; 1-hydroxy-prop-3yl;</li><li>1-hydroxy-but-4-yl, 1-hydroxy-but-3-yl, 1-hydroxy-but-2-yl, 1-hydroxy-but-1-yl, 2-hydroxy-but-4-yl, 2-hydroxy-but-3-yl, 2-hydroxy-but-3-yl, 2-hydroxy-but-4-yl;</li><li>1-methoxy-but-4-yl, 1-methoxy-but-3-yl, 1-methoxy-but-2-yl, 1-methoxy-but-1-yl, 2-methoxy-but-4-yl, 2-methoxy-but-3-yl, 2-methoxy-but-3-yl, 2-methoxy-but-4-yl,</li><li>Cyclopropyl, cyclopropyl-methyl, cyclopropyl-ethyl, cyclobutyl, cyclobutyl-methyl, cyclopentyl, cyclopentyl-methyl, cyclohexyl, cyclohexyl-methyl;</li><li>in particular cyclobutyl, cyclopentyl, i-propyl, sec. butyl, 3-methylbut-2-yl, 1-methoxy-prop-2-yl; 1-hydroxy-but-3-yl, cyclopropyl-methyl,</li></ul></li><li>(16) Compounds of the formula II, in which R₂₄ and R₂₃ together with the Z group to which they are attached form a 5-, or 6-membered, saturated, or mono- or polyunsaturated heterocyclic ring which has 1 or 2 additional ring heteroatoms which are the same or different and are selected from O, N and S;</li><li>(17) Compounds of the formula II, in which R₂₄ and R₂₃ together with the Z group to which they are attached form a 6-membered, saturated or mono- or polyunsaturated heterocyclic ring which has 1 additional ring heteroatom which is selected from O, N and S;</li><li>(18) Compounds of the formula II, in which R₂₄ and R₂₃ together with the Z group to which they are attached represent pyridyl or morpholinyl;</li><li>(19) combinations of the embodiments: (1) + (3), (1) + (4), (2) + (3), (2) + (4);</li><li>(20) combinations of the embodiments: (1) + (5), (1) + (6), (2) + (5), (2) + (6);</li><li>(21) combinations of the embodiments: (1) + (7), (1) + (8), (1) + (9), (2) + (7); (2) + (8), (2) + (9);</li><li>(22) Combinations of the embodiments: (1) + (10), (1) + (11), (1) + (12), (2) + (10), (2) + (11), (2) + (12);</li><li>(23) Combinations of the embodiments (1) + (13), (1) + (14), (1) + (15), (2) + (13), (2) + (14), (2) + (15);</li><li>(24) Combinations of the embodiments: (1) + (16), (1) + (17), (1) + (18), (2) + (16), (2) + (17), (2) + (18);</li><li>(25) combinations of the embodiments: (19) + (5), (19) + (6);</li><li>(26) combinations of the embodiments: (19) + (7), (19) + (8), (19) + (9);</li><li>(27) combinations of the embodiments: (19) + (10), (19) + (11), (19) + (12);</li><li>(28) combinations of the embodiments: (19) + (13), (19) + (14), (19) + (15);</li><li>(29) combinations of the embodiments: (25) + (7), (25) + (8), (25) + (9);</li><li>(30) combinations of the embodiments: (25) + (10), (25) + (11), (25) + (12);</li><li>(31) combinations of the embodiments: (25) + (13), (25) + (14), (25) + (15);</li><li>(32) combinations of the embodiments: (26) + (10), (26) + (11), (26) + (12);</li><li>(33) combinations of the embodiments: (26) + (13), (26) + (14), (26) + (15);</li><li>(34) combinations of the embodiments: (27) + (13), (27) + (14), (27) + (15);</li><li>(35) Combinations of the embodiments: (29) + (10), (29) + (11), (29) + (12)</li><li>(36) combinations of the embodiments: (29) + (13), (29) + (14), (29) + (15);</li><li>(37) combinations of the embodiments: (30) + (13), (30) + (14), (30) + (15);</li><li>(38) combinations of the embodiments: (35) + (13), (35) + (14), (35) + (15);</li><li>(39) combinations of the embodiments: (20) + (7), (20) + (8), (20) + (9);</li><li>(40) combinations of the embodiments: (20) + (10), (20) + (11), (20) + (12);</li><li>(41) combinations of the embodiments: (20) + (13), (20) + (14), (20) + (15);</li><li>(42) combinations of the embodiments: (20) + (16), (20) + (17), (20) + (18);</li><li>(43) combinations of the embodiments: (39) + (10), (39) + (11), (39) + (12);</li><li>(44) combinations of the embodiments: (39) + (13), (39) + (14), (39) + (15);</li><li>(45) combinations of the embodiments: (39) + (16), (39) + (17), (39) + (18);</li><li>(46) combinations of the embodiments: (40) + (13), (40) + (14), (40) + (15);</li><li>(47) combinations of the embodiments: (40) + (16), (40) + (17), (40) + (18);</li><li>(48) combinations of the embodiments: (43) + (13), (43) + (14), (43) + (15);</li><li>(49) combinations of the embodiments: (43) + (16), (43) + (17), (43) + (18);</li><li>(50) combinations of the embodiments: (21) + (10), (21) + (11), (21) + (12);</li><li>(51) combinations of the embodiments: (21) + (13), (21) + (14), (21) + (15);</li><li>(52) combinations of the embodiments: (21) + (16), (21) + (17), (21) + (18);</li><li>(53) combinations of the embodiments: (50) + (13), (50) + (14), (50) + (15);</li><li>(54) combinations of the embodiments: (50) + (16), (50) + (17), (50) + (18);</li><li>(55) combinations of the embodiments: (22) + (13), (22) + (14), (22) + (15);</li><li>(56) combinations of the embodiments: (22) + (16), (22) + (17), (22) + (18);</li><li>(57) Stereoisomeric forms of compounds of formula (II) when Z is NH;</li><li>(58) acid addition salts of compounds of the formula II, in particular of embodiments (1) to (57), if Z comprises a protonatable N atom;</li><li>(59) acid addition salts of compounds of the formula II, in particular of the embodiments (1) to (57), if Z comprises a protonated N atom, with organic mono- or polycarboxylic acids,</li><li>(60) Acid addition salts of compounds of the formula II, in particular of the embodiments (1) to (57), if Z comprises a protonatable N atom, with organic mono- or polycarboxylic acids, the carboxylic acid being selected from saturated or mono- or polyunsaturated C.₁-C₃₀-Monocarboxylic acids, saturated or mono- or polyunsaturated C₃-C₁₀-Di or tricarboxylic acids, where the carboxylic acid can be substituted one or more times with hydroxyl groups;</li><li>(6 1) Acid addition salts of compounds of the formula II, in particular of embodiments (1) to (57), if Z comprises a protonated N atom, with carboxylic acids, selected from fumaric acid, citric acid, malic acid, tartaric acid, succinic acid, lauric acid, myristic acid -, Palmitic or stearic acid and their stereoisomeric forms.</li></ol>

3.3 Compounds of the general formula III (structure type 3):

0033<chemistry id="chem0018" num="0018"><img file="EP3663366A2_D0018.tif" /></chemistry>selected from compounds of the following groups (1) to (63):<ol id="ol0005" compact="compact"><li>(1) Compounds of formula III, wherein R₃₄ represents H;</li><li>(2) Compounds of formula III, wherein R₃₅ represents H or halogen;</li><li>(3) Compounds of formula III, wherein R₃₁ for H, halogen, a straight-chain or branched C₁-C₆-Alkylgruppe, which optionally carries 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or a straight-chain or branched C₁-C₆-Alkoxy group, which optionally carries 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or C₁-C₆-Alkoxy groups;</li><li>(4) Compounds of formula III, wherein R₃₁ for H, halogen, a straight-chain or branched C₁-C₆-Alkyl group; or a straight-chain or branched C₁-C₆-Alkoxy group;</li><li>(5) Compounds of formula III, wherein R₃₁ represents H, methyl, ethyl, methoxy, ethoxy or halogen, in particular H, fluorine, chlorine, bromine, methyl or methoxy;</li><li>(6) Compounds of the formula III, in which the radicals R₃₂ and R₃₃ are identical or different and are selected from H; Halogen, straight-chain or branched C₁-C₆-Alkylgruppen, which optionally carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or straight-chain or branched C₁-C₆-Alkoxy groups, which may carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or C₁-C₆-Alkoxy groups;</li><li>(7) Compounds of the formula III, in which the radicals R₃₂ and R₃₃ are identical or different and are selected from H, halogen, straight-chain or branched C₁-C₆-Alkyl groups; or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>(8) Compounds of the formula III, in which the radicals R₃₂ and R₃₃ are identical or different and are selected from H, halogen, methyl or methoxy</li><li>(9) Compounds of the formula III, in which the adjacent radicals R₃₂ and R₃₃, together with the carbon atoms to which they are attached, form a 4-, 5-, 6- or 7-membered, mono- or polyunsaturated heterocyclic ring which may have 1, 2, 3, 4 or 5 identical or different substituents carries, which are selected from straight-chain or branched C₁-C₆Alkyl groups, and which has 1, 2 or 3 ring heteroatoms which are the same or different and are selected from O, N and S;</li><li>(10) Compounds of the formula III, in which the adjacent radicals R₃₂ and R₃₃, together with the carbon atoms to which they are attached, form a 5- or 6-membered, monounsaturated heterocyclic ring which has 1 or 2 ring heteroatoms which are identical or different and are selected from O, N and S;</li><li>(11) Compounds of the formula III, in which the adjacent radicals R₃₂ and R₃₃, together one of the groups -O-CH₂-O- or -O-CH₂-CH₂-O-, form;</li><li>(12) Compounds of the formula III, in which the radicals R₃₆ and R₃₇ are identical or different and are selected from straight-chain or branched C₁-C₆-Alkyl groups which may carry 1 or 2 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; mononuclear aryl, arylalkyl and heteroaryl groups, which may have 1 or 2 identical or different substituents selected from NH₂, OH, SH, halogen straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2 or 3 ring heteroatoms which are the same or different and are selected from O, N and S; and C₃-C₇-Cycloalkyl groups, which may have 1 or 2 identical or different substituents selected from NH₂, OH, SH, halogen straight-chain or branched C₁-C₆-Alkyl groups, or straight-chain or branched C₁-C₆-Alkoxy groups; where the cycloalkyl group optionally via a C₁-C₄Alkylene group is bonded and where optionally 1, 2 or 3 ring carbon atoms can be replaced by identical or different heteroatoms selected from O, N and S;</li><li>(13) Compounds of the formula III, in which the radicals R₃₆ and R₃₇ are identical or different and are selected from straight-chain or branched C₁-C₆-Alkyl groups; mononuclear aryl, arylalkyl and heteroaryl groups which optionally bear a substituent which is selected from NH₂, OH, SH, halogen, straight chain C₁-C₆-Alkyl groups and straight-chain C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2 or 3 ring heteroatoms which are the same or different and are selected from O, N and S; and C₃-C₇-Cycloalkyl groups, which may have 1 or 2 identical or different substituents selected from NH₂, OH, SH, halogen straight-chain or branched C₁-C₆-Alkyl groups, or straight-chain or branched C₁-C₆-Alkoxy groups; where the cycloalkyl group optionally via a C₁-C₄-Alkylene group is bound; and where optionally 1 or 2 ring carbon atoms can be replaced by identical or different heteroatoms selected from O and N;</li><li>(14) Compounds of the formula III, in which the radicals R₃₆ and R₃₇ are the same or different and are selected from Methyl, ethyl, n-prop-1-yl, n-prop-2-yl, n-butyl, sec.-butyl, i-butyl, tert-butyln-pentyl (amyl), 2-pentyl (sec-pentyl) , 3-pentyl, 2-methylbutyl, 3-methylbutyl (isopentyl or isoamyl), 3-methylbut-2-yl, 2-methylbut-2-yl; 2,2-dimethylpropyl (neopentyl); Cyclopropyl, cyclopropyl-methyl, cyclopropyl-ethyl, cyclobutyl, cyclobutyl-methyl, cyclopentyl, cyclopentyl-methyl, cyclohexyl, cyclohexyl-methyl; Cycloheptyl; Benzyl; Phenyl; 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl; 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl; 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl; 2-pyridyl, 3-pyridyl, 4-pyridyl, thiazolyl, oxazolyl, pyrazolyl, furanyl, morpholinyl, pyranyl, in particular cyclohexyl, cyclopropylmethyl, phenyl, benzyl, 4-chlorophenyl, 2-methylphenyl, 2-pyridyl, 2-thiazolyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl;</li><li>(15) Compounds of formula III, wherein X is selected from -C₁-C₄Alkylene groups; -C₂-C₄Alkenylene groups, and -OC₁-C₄Alkylene groups, or represents a chemical single bond;</li><li>(16) Compounds of formula III, wherein X is selected from -CH₂-, - CH₂-CH₂-, -CH = CH-; -O-CH₂-; - CH₂-O-; and a chemical bond.</li><li>(17) Combinations of the embodiments: (1) + (2);</li><li>(18) combinations of the embodiments: (1) + (3), (1) + (4), (1) +5);</li><li>(19) combinations of the embodiments: (1) + (6), (1) + (7), (1) + (8);</li><li>(20) combinations of the embodiments: (1) + (9), (1) + (10), (1) + (11);</li><li>(21) combinations of the embodiments: (1) + (12), (1) + (13), (1) + (14);</li><li>(22) Combinations of the embodiments: (1) + (15), (1) + (16);</li><li>(23) Combinations of the embodiments: (17) + (3), (17) + (4), (17) + (5)</li><li>(24) combinations of the embodiments: (17) + (6), (17) + (7), (17) + (8);</li><li>(25) combinations of the embodiments: (17) + (9), (17) + (10), (17) + (11);</li><li>(26) combinations of the embodiments: (17) + (12), (17) + (13), (17) + (14);</li><li>(27) combinations of the embodiments: (17) + (15), (17) + (16);</li><li>(28) combinations of the embodiments: (23) + (6), (23) + (7), (23) + (8);</li><li>(29) combinations of the embodiments: (23) + (9), (23) + (10), (23) + (11);</li><li>(30) combinations of the embodiments: (23) + (12), (23) + (13), (23) + (14);</li><li>(31) combinations of the embodiments: (23) + (15), (23) + (16);</li><li>(32) combinations of the embodiments: (28) + (12), (28) + (13), (28) + (14);</li><li>(33) combinations of the embodiments: (28) + (15), (28) + (16);</li><li>(34) combinations of the embodiments: (32) + (15), (32) + (16);</li><li>(35) combinations of the embodiments: (29) + (12), (29) + (13), (29) + (14);</li><li>(36) combinations of the embodiments: (29) + (15), (29) + (16);</li><li>(37) combinations of the embodiments: (35) + (15), (35) + (16);</li><li>(38) combinations of the embodiments: (30) + (15), (30) + (16);</li><li>(39) combinations of the embodiments: (24) + (12), (24) + (13), (24) + (14);</li><li>(40) combinations of the embodiments: (24) + (15), (24) + (16);</li><li>(41) combinations of the embodiments: (39) + (15), (39) + (16);</li><li>(42) combinations of the embodiments: (25) + (12), (25) + (13), (25) + (14);</li><li>(43) combinations of the embodiments: (25) + (15), (25) + (16);</li><li>(44) combinations of the embodiments: (42) + (15), (42) + (16);</li><li>(45) combinations of the embodiments: (26) + (15), (26) + (16);</li><li>(46) combinations of the embodiments: (18) + (6), (18) + (7), (18) + (8);</li><li>(47) combinations of the embodiments: (18) + (9), (18) + (10), (18) + (11);</li><li>(48) combinations of the embodiments: (18) + (12), (18) + (13), (18) + (14);</li><li>(49) combinations of the embodiments: (18) + (15), (18) + (16);</li><li>(50) combinations of the embodiments: (46) + (12), (46) + (13), (46) + (14);</li><li>(51) combinations of the embodiments: (46) + (15), (46) + (16);</li><li>(52) Combinations of the embodiments :; (50) + (15), (50) + (16)</li><li>(53) combinations of the embodiments: (47) + (12), (47) + (13), (47) + (14);</li><li>(54) combinations of the embodiments: (47) + (15), (47) + (16);</li><li>(55) combinations of the embodiments: (53) + (15), (53) + (16);</li><li>(56) combinations of the embodiments: (48) + (15), (48) + (16);</li><li>(57) combinations of the embodiments: (19) + (12), (19) + (13), (19) + (14);</li><li>(58) combinations of the embodiments: (19) + (15), (19) + (16);</li><li>(59) Combinations of the embodiments: (57) + (15), (57) + (16);</li><li>(60) combinations of the embodiments: (20) + (12), (20) + (13), (20) + (14);</li><li>(61) combinations of the embodiments: (20) + (15), (20) + (16);</li><li>(62) combinations of the embodiments: (60) + (15), (60) + (16);</li><li>(63) combinations of the embodiments: (21) + (15), (21) + (16);</li></ol>

4th Further configurations of the agents according to the invention (general part):

4.1 General information on areas of application and formulations of active compounds according to the invention

0034The active compounds according to the invention have a broad field of application in human cosmetic and care, in particular skin and hair care, but can also be used pharmacologically, in food and textile products, but also as repellents and as a component of insecticidal compositions.

0035The agents according to the invention can in particular be skin cosmetic, hair cosmetic, dermatological, hygienic or pharmaceutical agents. In particular, the active ingredients according to the invention, in particular having a cooling action, are used for skin and / or hair cosmetics or as oral care products.

0036The hair or skin care preparations according to the invention are in particular in the form of an emulsion, a dispersion, a suspension, in the form of an aqueous surfactant preparation, a milk, a lotion, a cream, a balm, an ointment, a gel, a granulate, a powder, a pen preparation such. B. a lipstick, a foam, an aerosol or a spray. Such formulations are well suited for topical preparations. Suitable emulsions are oil-in-water emulsions and water-in-oil emulsions or microemulsions.

0037As a rule, the hair or skin cosmetic preparation is used for application to the skin (topically) or the hair. "Topical preparations" are understood to mean those preparations which are suitable for applying the active substances to the skin in a fine distribution, such as, for example, in a form which can be absorbed by the skin. For this, z. B. aqueous and aqueous-alcoholic solutions, sprays, foams, foam aerosols, ointments, aqueous gels, emulsions of the O / W or W / O type, microemulsions or cosmetic stick preparations.

0038According to one embodiment of the cosmetic composition according to the invention, it contains a carrier. The preferred carrier is water, a gas, a water-based liquid, an oil, a gel, an emulsion or microemulsion, a dispersion or a mixture thereof. The carriers mentioned show good skin tolerance. Aqueous gels, emulsions or microemulsions are particularly advantageous for topical preparations.

0039The teaching according to the invention also includes the use of the active ingredients described herein in pharmaceutical compositions for the treatment of an individual, preferably a mammal, in particular a human, useful or domestic animal. For this purpose, the active substances are administered in the form of pharmaceutical compositions which comprise a pharmaceutically acceptable excipient with at least one active substance according to the invention and optionally further active substances. These compositions can be administered, for example, by the oral, rectal, transdermal, subcutaneous, intravenous, intramuscular or intranasal routes.

0040Examples of suitable pharmaceutical formulations are solid pharmaceutical forms, such as powders, powders, granules, tablets, troches, sachets, cachets, dragees, capsules such as hard and soft gelatin capsules, suppositories or vaginal pharmaceutical forms, semi-solid pharmaceutical forms such as ointments, creams, hydrogels, pastes or plasters and liquid pharmaceutical forms, such as solutions, emulsions, in particular oil-in-water emulsions, suspensions, for example lotions, injection and infusion preparations, Eye and ear drops. Implanted delivery devices can also be used for the administration of inhibitors according to the invention. Liposomes, microspheres or polymer matrices can also be used.

0041In the preparation of compositions according to the invention, active compounds according to the invention are usually mixed or diluted with an excipient. Excipients can be solid, semi-solid or liquid materials that serve as vehicles, carriers or media for the active ingredient. The active ingredient content (one or more active ingredients according to the invention contained at the same time) can vary within a wide range and is approximately, based on the total weight of the composition, in the ppm range of approximately 0.05 ppm - &lt;0.1 ppm and 0.1 up to 1000 ppm (ie 0.00001 to 0.1% by weight), such as 1 to 800 ppm or 100 to 500 ppm or in the range from 0.1 to 50, 1 to 30 or 2 to 10% by weight .

0042Suitable excipients include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, starches, acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methyl cellulose. Furthermore, the formulations can be pharmaceutically acceptable carriers or customary auxiliaries, such as lubricants, for example tallow, magnesium stearate and mineral oil; Wetting agents; emulsifying and suspending agents; preservatives such as methyl and propyl hydroxybenzoates; Antioxidants; Anti-irritants; Chelating agents; Coating aids; Emulsion stabilizers film formers; Gelling agent; Odor masking agents; Taste corrections; Resins; Hydrocolloids; Solvents; Solubilizer; Neutralizing agents; Permeation accelerator; Pigments; quaternary ammonium compounds; Refatting and overfatting agents; Ointment, cream or oil base materials; Silicone derivatives; Spreading aids; Stabilizers; Sterilants; Suppository basics; Tablet excipients such as binders, fillers, lubricants, disintegrants or coatings; Blowing agent; Desiccants; Opacifiers; Thickeners; Waxes; Plasticizers; Include white oils. A relevant design is based on professional knowledge, such as in <nplcit id="ncit0020" npl-type="b"><text>Fiedler, HP, Lexicon of auxiliaries for pharmacy, cosmetics and related areas, 4th edition, Aulendorf: ECV-Editio-Kantor-Verlag, 1996</text></nplcit>, or <nplcit id="ncit0021" npl-type="b"><text>Hager's Handbook of Pharmaceutical Practice, Springer Verlag</text></nplcit>, Heidelberg is shown.

0043In addition to the usual additives or auxiliaries, the agents according to the invention can additionally contain cosmetically and / or dermatologically and / or pharmacologically active substances.

0044The following are non-limiting examples of suitable further active ingredients: Suitable cosmetically and / or dermatologically active ingredients are e.g. B. coloring agents, skin and hair pigmentation agents, tinting agents, tanning agents, bleaching agents, keratin-curing agents, antimicrobial agents, light filter agents, repellent agents, hyperemising agents, keratolytic and keratoplastic agents, antidandruff agents, anti-inflammatory agents, keratinizing agents, antioxidants as free radical scavengers active substances, skin moisturizing or moisturizing substances, moisturizing active substances, anti-rythematous or anti-allergic active substances, branched fatty acids, such as 18-methyleicosanoic acid, and mixtures thereof.

0045Artificially tanning agents that are suitable for tanning the skin without natural or artificial radiation with UV rays; these are e.g. B. dihydroxyacetone, alloxan and walnut shell extract. Suitable keratin-curing substances are usually active substances, such as those used in antiperspirants, such as. As potassium aluminum sulfate, aluminum hydroxychloride, aluminum lactate etc.

0046Antimicrobial agents that are used to destroy microorganisms or to inhibit their growth. They serve both as a preservative and as a deodorizing substance, which reduces the development or intensity of body odor. These include e.g. B. conventional preservatives known to those skilled in the art, such as p-hydroxybenzoic acid ester, imidazolidinyl urea, formaldehyde, sorbic acid, benzoic acid, salicylic acid etc. Such deodorant substances are e.g. B. zinc ricinoleate, triclosan, undecylenic acid alkylolamides, citric acid triethyl ester, chlorhexidine etc.

0047Suitable auxiliaries and additives for the production of hair cosmetic or skin cosmetic preparations are known to the person skilled in the art and can be obtained from<nplcit id="ncit0022" npl-type="b"><text> Cosmetics manuals, for example Schrader, basics and formulations of cosmetics, Hüthig Verlag, Heidelberg, 1989, ISBN 3-7785-1491-1</text></nplcit>, can be removed. The auxiliaries and additives are preferably cosmetically and / or pharmaceutically acceptable auxiliaries. The excipients known to be usable in the field of pharmacy, food technology and related fields are pharmaceutically acceptable, in particular the excipients listed in relevant pharmacopoeias (e.g. DAB, Ph. Eur., BP, NF) and other excipients, the properties of which are not physiological oppose.

0048Suitable auxiliaries can be: Lubricants, wetting agents, emulsifying and suspending agents, preserving agents, antioxidants, anti-irritants, chelating agents, emulsion stabilizers, film formers, gelling agents, odor masking agents, hydrocolloids, solvents, solubilizers, neutralizing agents, permeation accelerators, pigments, quaternary ammonium compounds and refatting agents, re-fatty acids, superfatting agents, re-fatty acids, refatting agents - or oil base materials, silicone derivatives, stabilizers, sterilants, blowing agents, Desiccants, opacifiers, thickeners, waxes, plasticizers, white oil. A relevant design is based on professional knowledge, such as that in<nplcit id="ncit0023" npl-type="b"><text>Fiedler, HP Lexicon of auxiliaries for pharmacy, cosmetics and related areas, 4th ed., Aulendorf: ECV-Editio-Kantor-Verlag, 1996</text></nplcit>, are shown.

0049Other suitable additives are chosen from perfume oils, hair polymers, hair and Hautkonditionern, graft polymers, water-soluble or dispersible silicone-containing polymers, light protection agents, bleaching agents, care agents, colorants, tinting agents, tanning agents, dyes, consistency regulators, humectants, refatting agents, collagen, protein hydrolysates, lipids, antioxidants , Defoamers, antistatic agents, emollients, plasticizers, peroxide decomposers.

0050Examples of suitable auxiliaries and additives are: (1) Antioxidants selected from amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. β-carotene, lycopene) and their derivatives, chlorogenic acid and their derivatives, lipoic acid and their derivatives (e.g. Dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thiorodoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl, and lauryl -, Palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (e.g. B. Buthioninsulfoximine, homocysteine ​​sulfoximine, buthionine sulfone, penta-, hexa-, heptathionine sulfoximine), especially in very low, compatible dosages (e.g. pmol to µmol / kg range), also (metal) chelators (e.g. α-hydroxy fatty acids, Palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and its derivatives (e.g. sodium ascorbate, ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherol and derivatives (e.g. Vitamin E acetate, tocotrienol), vitamin A and derivatives (vitamin A palmitate) as well as coniferyl benzoate of benzoin, rutinic acid and its derivatives, α-glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butylated hydroxytoluene, butylated hydroxyanisole, trihydroxyhydroxy acid, Uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (e.g. ZnO, ZnSO₄), Selenium and its derivatives (e.g. selenium methionine), stilbenes and their derivatives (e.g. stilbene oxide, trans-stilbene oxide). (2) Peroxide decomposer, ie compounds which are able to decompose peroxides, particularly preferably lipid peroxides. This includes organic substances, such as. B. pyridine-2-thiol-3-carboxylic acid, 2-methoxy-pyrimidinol-carboxylic acids, 2-methoxy-pyridinecarboxylic acids, 2-dimethylamino-pyrimidinolcarboxylic acids, 2-dimethylamino-pyridinecarboxylic acids. (3) thickeners, such as crosslinked polyacrylic acids and their derivatives, polysaccharides and their derivatives, such as xanthan gum, agar agar, alginates or tyloses, cellulose derivatives, e.g. B. carboxymethyl cellulose or hydroxycarboxymethyl cellulose, fatty alcohols, monoglycerides and fatty acids, polyvinyl alcohol and polyvinyl pyrrolidone. In particular, nonionic thickeners are used. (4) Preservatives listed below with their E number<tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="13mm" /><colspec colnum="2" colname="col2" colwidth="70mm" /><colspec colnum="3" colname="col3" colwidth="13mm" /><colspec colnum="4" colname="col4" colwidth="46mm" /><tbody><row><entry>E 200</entry><entry>Sorbic acid</entry><entry>E 227</entry><entry>Calcium bisulfite</entry></row><row><entry>E 201</entry><entry>Sodium sorbate</entry><entry>E 228</entry><entry>Potassium hydrogen sulfite)</entry></row><row><entry>E 202</entry><entry>Potassium sorbate</entry><entry>E 230</entry><entry>Biphenyl (diphenyl)</entry></row><row><entry>E 203</entry><entry>Calcium sorbate</entry><entry>E 231</entry><entry>Orthophenylphenol</entry></row><row><entry>E 210</entry><entry>Benzoic acid</entry><entry>E 232</entry><entry>Sodium orthophenylphenolate</entry></row><row><entry>E 211</entry><entry>Sodium benzoate</entry><entry>E 233</entry><entry>Thiabendazole</entry></row><row><entry>E 212</entry><entry>Potassium benzoate</entry><entry>E 235</entry><entry>Natamycin</entry></row><row><entry>E 213</entry><entry>Calcium benzoate</entry><entry>E 236</entry><entry>Formic acid</entry></row><row><entry>E 214</entry><entry>p-Hydroxybenzoic acid ethyl ester</entry><entry>E 237</entry><entry>Sodium formate</entry></row><row><entry>E 215</entry><entry>p-Hydroxybenzoic acid ethyl ester Na salt</entry><entry>E 238</entry><entry>Calcium formate</entry></row><row><entry>E 216</entry><entry>p-Hydroxybenzoic acid n-propyl ester</entry><entry>E 239</entry><entry>Hexamethylenetetramine</entry></row><row><entry>E 217</entry><entry>p-Hydroxybenzoic acid n-propyl ester Na salt</entry><entry>E 249</entry><entry>Potassium nitrite</entry></row><row><entry>E 218</entry><entry>p-Hydroxybenzoic acid methyl ester</entry><entry>E 250</entry><entry>Sodium nitrite</entry></row><row><entry>E 219</entry><entry>p-Hydroxybenzoic acid methyl ester Na salt</entry><entry>E 251</entry><entry>Sodium nitrate</entry></row><row><entry>E 220</entry><entry>Sulfur ioxid</entry><entry>E 252</entry><entry>Potassium nitrate</entry></row><row><entry>E 221</entry><entry>Sodium sulfite</entry><entry>E 280</entry><entry>Propionic acid</entry></row><row><entry>E 222</entry><entry>Sodium hydrogensulfite</entry><entry>E 281</entry><entry>Sodium propionate</entry></row><row><entry>E 223</entry><entry>Sodium disulfite</entry><entry>E 282</entry><entry>Calcium propionate</entry></row><row><entry>E 224</entry><entry>Potassium disulfite</entry><entry>E 283</entry><entry>Potassium propionate</entry></row><row><entry>E 226</entry><entry>Calcium sulfite</entry><entry>E 290</entry><entry>Carbon dioxide</entry></row></tbody></tgroup></table></tables>Furthermore, preservatives or preservation aids customary in cosmetics are suitable according to the invention, such as dibromodicyanobutane (2-bromo-2-bromomethylglutarodinitrile), 3-iodo-2-propynylbutylcarbamate, 2-bromo-2-nitro-propane-1,3-diol, imidazolidinyl- urea, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-chloroacetamide, benzalkonium chloride, benzyl alcohol, formaldehyde releaser. Furthermore, phenylhydroxyalkyl ethers, in particular the compound known under the name phenoxyethanol, are suitable as preservatives on account of their bactericidal and fungicidal effects on a number of microorganisms. Other germ-inhibiting agents are also suitable for being incorporated into the preparations according to the invention. Examples of advantageous substances are 2,4,4'-trichloro-2'-hydroxydiphenyl ether (irgasane), 1,6-di- (4-chlorophenylbiguanido) hexane (chlorhexidine), 3,4,4'-trichlorocarbanilide, quaternary ammonium compounds , Clove oil, mint oil, thyme oil, triethyl citrate, farnesol (3,7,11-trimethyl-2,6,10-dodecatriën-1-ol) as well as those in the patent publications <patcit id="pcit0014" dnum="DE3740186"><text>DE-37 40 186</text></patcit>, <patcit id="pcit0015" dnum="DE3938140"><text>DE-39 38 140</text></patcit>, <patcit id="pcit0016" dnum="DE4204321"><text>DE-42 04 321</text></patcit>, <patcit id="pcit0017" dnum="DE4229707"><text>DE-42 29 707</text></patcit>, <patcit id="pcit0018" dnum="DE4309372"><text>DE-43 09 372</text></patcit>, <patcit id="pcit0019" dnum="DE4411664"><text>DE-44 11 664</text></patcit>, <patcit id="pcit0020" dnum="DE19541967"><text>DE-195 41 967</text></patcit>, <patcit id="pcit0021" dnum="DE19543695"><text>DE-195 43 695</text></patcit>, <patcit id="pcit0022" dnum="DE19543696"><text>DE-195 43 696</text></patcit>, <patcit id="pcit0023" dnum="DE19547160"><text>DE-195 47 160</text></patcit>, <patcit id="pcit0024" dnum="DE19602108"><text>DE-196 02 108</text></patcit>, <patcit id="pcit0025" dnum="DE19602110"><text>DE-196 02 110</text></patcit>, <patcit id="pcit0026" dnum="DE19602111"><text>DE-196 02 111</text></patcit>, <patcit id="pcit0027" dnum="DE19631003"><text>DE-196 31 003</text></patcit>, <patcit id="pcit0028" dnum="DE19631004"><text>DE-196 31 004</text></patcit> and <patcit id="pcit0029" dnum="DE19634019"><text>DE-196 34 019</text></patcit> and the patents <patcit id="pcit0030" dnum="DE4229737"><text>DE-42 29 737</text></patcit>, <patcit id="pcit0031" dnum="DE4237081"><text>DE-42 37 081</text></patcit>, <patcit id="pcit0032" dnum="DE4324219"><text>DE-43 24 219</text></patcit>, <patcit id="pcit0033" dnum="DE4429467"><text>DE-44 29 467</text></patcit>, <patcit id="pcit0034" dnum="DE4423410"><text>DE-44 23 410</text></patcit> and <patcit id="pcit0035" dnum="DE19516705"><text>DE-195 16 705</text></patcit> described active ingredients or combinations of active ingredients. Sodium hydrogen carbonate can also be used advantageously. Antimicrobial polypeptides can also be used. (5) Light filter agents that absorb UV rays in the UV-B and / or UV-A range. Suitable UV filters are e.g. B. 2,4,6-Triaryl-1,3,5-triazines, in which the aryl groups can each carry at least one substituent, which is preferably selected from hydroxy, alkoxy, especially methoxy, alkoxycarbonyl, especially methoxycarbonyl and ethoxycarbonyl, and mixtures thereof. Also suitable are p-aminobenzoic acid esters, cinnamic acid esters, benzophenones, camphor derivatives and pigments which block UV rays, such as titanium dioxide, talc and zinc oxide. Any UV-A and UV-B filter substances can be considered as UV filter substances. Examples include:<tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="125mm" /><colspec colnum="3" colname="col3" colwidth="32mm" /><thead><row><entry valign="top">No.</entry><entry valign="top">material</entry><entry valign="top">CAS number (= Acid)</entry></row></thead><tbody><row><entry>1</entry><entry>4-aminobenzoic acid</entry><entry>150-13-0</entry></row><row><entry>2</entry><entry>3- (4'-Trimethylammonium) benzylidenebornan-2-one methyl sulfate</entry><entry>52793-97-2</entry></row><row><entry>3</entry><entry>3,3,5-trimethylcyclohexyl salicylate (homosalatum)</entry><entry>118-56-9</entry></row><row><entry>4</entry><entry>2-hydroxy-4-methoxy-benzophenone (oxybenzonum)</entry><entry>131-57-7</entry></row><row><entry>5</entry><entry>2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium u. Triethanolamine salts</entry><entry>27503-81-7</entry></row><row><entry>6</entry><entry>3,3 '- (1,4-phenylenedimethine) -bis (7,7-dimethyl-2-oxobicyclo [2.2.1] heptane-1-methanesulfonic acid) and their salts</entry><entry>90457-82-2</entry></row><row><entry>7</entry><entry>4-bis (polyethoxy) amino benzoic acid polyethoxy ethyl ester</entry><entry>113010-52-9</entry></row><row><entry>8</entry><entry>2-ethylhexyl 4-dimethylamino-benzoate</entry><entry>21245-02-3</entry></row><row><entry>9</entry><entry>2-ethylhexyl salicylic acid</entry><entry>118-60-5</entry></row><row><entry>10</entry><entry>4-methoxy-cinnamic acid re-2-isoa mylester</entry><entry>71617-10-2</entry></row><row><entry>11</entry><entry>2-ethylhexyl 4-methoxycinnamate</entry><entry>5466-77-3</entry></row><row><entry>12</entry><entry>2-Hydroxy-4-methoxy-benzophenone-5-sulfonic acid (Sulisobenzonum) and the sodium salt</entry><entry>4065-45-6</entry></row><row><entry>13</entry><entry>3- (4'-sulfobenzylidene) -bornan-2-one and salts</entry><entry>58030-58-6</entry></row><row><entry>14</entry><entry>3-Benzylidenbornan-2-one</entry><entry>16087-24-8</entry></row><row><entry>15</entry><entry>1- (4'-isopropylphenyl) -3-phenylpropane-1,3-dione</entry><entry>63260-25-9</entry></row><row><entry>16</entry><entry>4-isopropylbenzyl salicylate</entry><entry>94134-93-7</entry></row><row><entry>17</entry><entry>3-imidazol-4-yl-acrylic acid and its ethyl ester</entry><entry>104-98-3</entry></row><row><entry>18</entry><entry>Ethyl 2-cyano-3,3-diphenylacrylate</entry><entry>5232-99-5</entry></row><row><entry>19</entry><entry>2'-Cyano-3,3-diphenylacrylic acid 2'-ethylhexyl ester</entry><entry>6197-30-4</entry></row><row><entry>20</entry><entry>Menthyl o-aminobenzoate or: 5-methyl-2- (1-methylethyl) -2-aminobenzoate</entry><entry>134-09-8</entry></row><row><entry>21</entry><entry>Glyceryl p-aminobenzoate or: 4-aminobenzoic acid 1-glyceryl ester</entry><entry>136-44-7</entry></row><row><entry>22</entry><entry>2,2'-dihydroxy-4-methoxybenzophenone (dioxybene zone)</entry><entry>131-53-3</entry></row><row><entry>23</entry><entry>2-hydroxy-4-methoxy-4-methylbenzophenone (mexenone)</entry><entry>1641-17-4</entry></row><row><entry>24</entry><entry>Triethanolamine salicylate</entry><entry>2174-16-5</entry></row><row><entry>25</entry><entry>Dimethoxyphenylglyoxalic acid or: 3,4-dimethoxyphenylglyoxalic acid sodium</entry><entry>4732-70-1</entry></row><row><entry>26</entry><entry>3- (4'Sulfobenzylidene) -bornan-2-one and its salts</entry><entry>56039-58-8</entry></row><row><entry>27</entry><entry>4-tert-butyl-4'-methoxy-dibenzoylmethane</entry><entry>70356-09-1</entry></row><row><entry>28</entry><entry>2,2 ', 4,4'-tetrahydroxybenzophenone</entry><entry>131-55-5</entry></row><row><entry>29</entry><entry>2,2'-methylene-bis- [6- (2H-benzotriazol-2-yl) -4- (1,1,3,3, -tetramethylbutyl) phenol]</entry><entry>103597-45-1</entry></row><row><entry>30</entry><entry>2,2 '- (1,4-phenylene) bis-1H-benzimidazole-4,6-disulfonic acid, Na salt</entry><entry>180898-37-7</entry></row><row><entry>31</entry><entry>2,4-bis- [4- (2-ethylhexyloxy) -2-hydroxy] phenyl-6- (4-methoxyphenyl) - (1,3,5) triazine</entry><entry>187393-00-6</entry></row><row><entry>32</entry><entry>3- (4-methylbenzylidene) camphor</entry><entry>36861-47-9</entry></row><row><entry>33</entry><entry>4-bis (polyethoxy) paraaminobenzoic acid polyethoxyethyl ester</entry><entry>113010-52-9</entry></row><row><entry>34</entry><entry>2,4-dihydroxybenzophenone</entry><entry>131-56-6</entry></row><row><entry>35</entry><entry>2,2'-dihydroxy-4,4'-dimethoxybenzophenone-5,5'-disodium sulfonate</entry><entry>3121-60-6</entry></row><row><entry>36</entry><entry>Benzoic acid, 2- [4- (diethylamino) -2-hydroxybenzoyl] -, hexyl ester</entry><entry>302776-68-7</entry></row><row><entry>37</entry><entry>2- (2H-Benzotriazol-2-yl) -4-methyl-6- [2-methyl-3- [1,3,3,3-tetramethyl-1 - [(trimethylsilyl) oxy] disiloxanyl] propyl] phenol</entry><entry>155633-54-8</entry></row><row><entry>38</entry><entry>1,1 - [(2,2'-Dimethylpropoxy) carbonyl] -4,4-diphenyl-1,3-butadiene</entry><entry>363602-15-7</entry></row></tbody></tgroup></table></tables>The cosmetic and dermatological preparations according to the invention can advantageously also contain UV-blocking inorganic pigments based on metal oxides and / or other metal compounds which are sparingly soluble or insoluble in water, selected from the group of the oxides of zinc (ZnO), titanium (TiO₂), Iron (e.g. Fe₂CO₃), Zirconium (ZrO₂), Silicon (SiO₂), Manganese (e.g. MnO), aluminum (Al₂O₃), Cers (e.g. Ce₂O₃), Mixed oxides of the corresponding metals and mixtures of such oxides. The inorganic pigments can be in coated form, ie they are treated on the surface. This surface treatment can consist, for example, in that the pigments are processed in a manner known per se, as in<patcit id="pcit0036" dnum="DE3314742A"><text>DE-A-33 14 742</text></patcit> described, are provided with a thin hydrophobic layer. (6) Repellent agents, ie compounds that are able to deter or drive away certain animals, especially insects, from humans. This includes e.g. B. 2-ethyl-1, 3-hexanediol, N, N-diethyl-m-toluamide etc. (7) Suitable hyperemising substances that stimulate blood circulation to the skin are e.g. B. essential oils such as mountain pine extract, lavender extract, rosemary extract, juniper berry extract, horse chestnut extract, birch leaf extract, hay flower extract, ethyl acetate, camphor, menthol, peppermint oil, rosemary extract, eucalyptus oil etc. (8) Suitable keratolytic and keratoplastic substances are e.g. B. salicylic acid, calcium thioglycolate, thioglycolic acid and its salts, sulfur, etc. Suitable antidandruff agents are e.g. B. Sulfur, sulfur polyethylene glycol sorbitan monooleate, sulfur ricinol polyethoxylate, zinc pyrithione, aluminum pyrithione etc. (9) Suitable anti-inflammatory drugs that counteract skin irritation are e.g. B. allantoin, bisabolol, dragosantol, chamomile extract, panthenol etc. (10) Cosmetically or pharmaceutically acceptable polymers, such as cationic, amphoteric and neutral polymers. Suitable polymers are e.g. B. cationic polymers with the name Polyquaternium according to INCI, z. B. Copolymers of vinylpyrrolidone / N-vinylimidazolium salts (Luviquat FC, Luviquat HM, Luviquat MS, Luviquat Care), copolymers of N-vinylpyrrolidone / dimethylaminoethyl methacrylate, quaternized with diethyl sulfate (Luviquat PQ 11), copolymers of N / Nonon-caprolate Vinylimidazolium salts (Luviquat E Hold), cationic cellulose derivatives (Polyquaternium-4 and -10), acrylamido copolymers (Polyquaternium-7) and chitosan. Suitable cationic (quaternized) polymers are also merquat (polymer based on dimethyldiallylammonium chloride), gafquat (quaternary polymers formed by the reaction of polyvinylpyrrolidone with quaternary ammonium compounds), polymer JR (hydroxyethyl cellulose with cationic groups) and cationic plant-based polymers, e.g. B. guar polymers, such as the Jaguar brands of the company Rhodia. Other suitable polymers are also neutral polymers, such as polyvinylpyrrolidones, copolymers of N-vinylpyrrolidone and vinyl acetate and / or vinyl propionate, polysiloxanes, polyvinylcaprolactam and other copolymers with N-vinylpyrrolidone, polyethyleneimines and their salts, polyvinylamines and their salts, cellulose derivatives, polyasparagine derivatives, polyasparas derivatives . These include, for example, Luviflex ® Swing (partially saponified copolymer of polyvinyl acetate and polyethylene glycol, from BASF). Suitable polymers are also nonionic, water-soluble or water-dispersible polymers or oligomers, such as polyvinylcaprolactam, e.g. B. Luviskol ® Plus (BASF), or polyvinylpyrrolidone and their copolymers, in particular with vinyl esters, such as vinyl acetate, for. B. Luviskol ® VA 37 (BASF), polyamides, e.g. B. based on itaconic acid and aliphatic diamines, such as z. B. in the<patcit id="pcit0037" dnum="DE4333238A"><text>DE-A-43 33 238</text></patcit> are described. Suitable polymers are also amphoteric or zwitterionic polymers, such as the octylacrylamide / methyl methacrylate / tert.-butylaminoethyl methacrylate-hydroxypropyl methacrylate copolymers available under the names Amphomer (National Starch), and zwitterionic polymers, as described, for example, in the German patent applications <patcit id="pcit0038" dnum="DE3929973"><text>DE39 29 973</text></patcit>, <patcit id="pcit0039" dnum="DE2150557"><text>DE 21 50 557</text></patcit>, <patcit id="pcit0040" dnum="DE2817369"><text>DE28 17 369</text></patcit> and <patcit id="pcit0041" dnum="DE3708451"><text>DE 3708 451</text></patcit> are disclosed. Acrylamidopropyltrimethylammonium chloride / acrylic acid or methacrylic acid copolymers and their alkali and ammonium salts are preferred zwitterionic polymers. Other suitable zwitterionic polymers are methacroylethylbetaine / methacrylate copolymers, which are commercially available under the name Amersette (AMERCHOL), and copolymers of hydroxyethyl methacrylate, methyl methacrylate, N, N-dimethylaminoethyl methacrylate and acrylic acid (Jordapon (D)). Suitable polymers are also nonionic, siloxane-containing, water-soluble or dispersible polymers, e.g. B. polyether siloxanes such as Tegopren ® (Goldschmidt) or Besi (Wacker).

0051Individual special application forms of active substances according to the invention are explained in more detail below by way of example.

4.2 Cooling skin and hair care products

0052According to a preferred embodiment, the agents according to the invention are a cooling skin or hair care or cleaning agent.

0053Preferred skin or hair cleaning agents are soaps of liquid to gel-like consistency, such as transparent soaps, luxury soaps, deodorant soaps, cream soaps, baby soaps, skin protection soaps, abrasive soaps and syndets, pasty soaps, greasy soaps and washing pastes, peeling soaps, moist wipes, liquid washing, showering and bathing preparations , such as washing lotions, shower baths and gels, bubble baths, oil baths and scrub preparations, shaving foams, lotions and creams.

0054According to a further preferred embodiment, the agents according to the invention are a shower gel, a shampoo formulation or a bath preparation. Such formulations contain at least one active ingredient according to the invention and usually anionic surfactants as base surfactants and amphoteric and / or nonionic surfactants as cosurfactants. Further suitable active substances and / or auxiliary substances are generally selected from lipids, perfume oils, dyes, organic acids, preservatives and antioxidants as well as thickeners / gel formers, skin conditioners and humectants.

0055In principle, the active ingredient content can vary over a wide range, for example 0.00001 to 50% by weight, in particular 0.001 to 10% by weight or 0.005 to 1% by weight.

i) Special configurations for agents for application to the skin:

0056Suitable skin cosmetic agents are e.g. B. face lotions, face masks, deodorants and other cosmetic lotions. Agents for use in decorative cosmetics include, for example, concealers, theater paints, mascara and eye shadows, lipsticks, eyeliner pencils, eyeliner, blush, powder and eyebrow pencils.

0057In addition, the dermatological agents according to the invention can be used in nose strips for pore cleaning, in anti-acne agents, repellents, shaving agents, after- and pre-shave care agents, after-sun care agents, hair removal agents, hair colorants, intimate care agents, foot care agents and in baby care.

0058The skin care products according to the invention are in particular W / O or O / W skin creams, day and night creams, eye creams, face creams, anti-wrinkle creams, sunscreen creams, moisturizing creams, bleaching creams, self-tanning creams, vitamin creams, skin lotions and moisturizing lotions.

0059Skin cosmetic and dermatological agents contain in particular at least one active ingredient according to the invention in a proportion of about 0.0001 to 50 wt .-%, such as. B. 0.001 to 10 wt .-%, in particular 0.005 to 0.1 wt .-%, based on the total weight of the agent.

0060Depending on the area of ​​application, the skin cosmetics according to the invention can be used in a form suitable for skin care, such as, for. B. as a cream, foam, gel, stick, mousse, milk, spray (pump spray or spray containing blowing agent) or lotion.

0061In addition to the active ingredients according to the invention and suitable carriers, the skin cosmetic preparations can also contain other active ingredients and auxiliaries customary in skin cosmetics, as described above. These preferably include emulsifiers, preservatives, perfume oils, cosmetic active ingredients such as phytantriol, vitamins A, E and C, retinol, bisabolol, panthenol, light stabilizers, bleaches, colorants, tinting agents, tanning agents, collagen, enzymes, protein hydrolyzates, stabilizers, pH regulators , Dyes, salts, thickeners, gelling agents, consistency agents, silicones, humectants, moisturizers and other common additives.

0062Preferred oil and fat components of the skin cosmetic and dermatological agents are the aforementioned mineral and synthetic oils, such as. B. paraffins, silicone oils and aliphatic hydrocarbons with more than 8 carbon atoms, animal and vegetable oils, such as. B. sunflower oil, coconut oil, avocado oil, olive oil, lanolin, or waxes, fatty acids, fatty acid esters, such as. B. Triglycerides from C₆-C₃₀Fatty acids, wax esters, such as B. jojoba oil, fatty alcohols, petroleum jelly, hydrogenated lanolin and acetylated lanolin and mixtures thereof.

0063To set certain properties such. B. Improving the feel, the spreading behavior, the water resistance and / or the binding of active ingredients and auxiliary substances such as pigments, the skin cosmetic and dermatological preparations can also contain conditioning substances based on silicone compounds. Suitable silicone compounds are, for example, polyalkylsiloxanes, polyarylsiloxanes, polyarylalkylsiloxanes, polyether siloxanes or silicone resins.

0064The cosmetic or dermatological preparations are produced by customary methods known to the person skilled in the art.

0065To produce the dermatological agents according to the invention, the active ingredients can be mixed or diluted with a suitable excipient. Excipients can be solid, semi-solid or liquid materials that can serve as vehicles, carriers or media for the active ingredient. If desired, further auxiliaries are admixed in the manner known to the person skilled in the art. The polymers and dispersions are furthermore suitable as auxiliaries in pharmacy, preferably as or in coating compositions or binders for solid pharmaceutical forms. They can also be used in creams and as tablet coatings and tablet binders.

0066The cosmetic and dermatological agents are preferably in the form of emulsions, in particular in the form of water-in-oil (W / O) or oil-in-water (O / W) emulsions. However, it is also possible to choose other types of formulation, for example gels, oils, oleogels, multiple emulsions, for example in the form of W / O / W or O / W / O emulsions, anhydrous ointments or ointment bases, etc. Emulsifier-free formulations such as hydrodispersions, hydrogels or a Pickering emulsion are also advantageous embodiments.

0067Emulsions are prepared by known methods. In addition to at least one active ingredient according to the invention, the emulsions generally contain customary constituents, such as fatty alcohols, fatty acid esters and in particular fatty acid triglycerides, fatty acids, lanolin and derivatives thereof, natural or synthetic oils or waxes and emulsifiers in the presence of water. The selection of the additives specific to the type of emulsion and the preparation of suitable emulsions is described, for example, in <nplcit id="ncit0024" npl-type="b"><text>Schrader, basics and formulations of cosmetics, Hüthig Buch Verlag, Heidelberg, 2nd edition, 1989</text></nplcit>, third part, to which express reference is hereby made.

0068A suitable emulsion as a W / O emulsion, e.g. B. for a skin cream, etc., generally contains an aqueous phase which is emulsified in an oil or fat phase by means of a suitable emulsifier system. A polyelectrolyte complex can be used to provide the aqueous phase.

0069Preferred fat components which can be contained in the fat phase of the emulsions are: hydrocarbon oils, such as paraffin oil, purcellin oil, perhydrosqualene and solutions of microcrystalline waxes in these oils; animal or vegetable oils, such as sweet almond oil, avocado oil, calophylum oil, lanolin and derivatives thereof, castor oil, sesame oil, olive oil, jojoba oil, karite oil, hoplostethus oil, mineral oils, the distillation of which begins at atmospheric pressure at approx. 250 ° C and its distillation end point is 410 ° C, such as. B. Vaseline oil, esters of saturated or unsaturated fatty acids, such as alkyl myristates, e.g. B. i-propyl, butyl or cetyl myristate, hexadecyl stearate, ethyl or i-propyl palmitate, octanoic or decanoic acid triglycerides and cetylricinoleate.

0070The fat phase can also contain silicone oils soluble in other oils, such as dimethylpolysiloxane, methylphenylpolysiloxane and the silicone glycol copolymer, fatty acids and fatty alcohols.

0071In addition to the active compounds according to the invention, waxes can also be used, such as. B. Carnauba wax, candililla wax, beeswax, microcrystalline wax, ozokerite wax and Ca, Mg and Al oleates, myristates, linoleates and stearates.

0072Furthermore, an emulsion according to the invention can be present as an O / W emulsion. Such an emulsion usually contains an oil phase, emulsifiers which stabilize the oil phase in the water phase and an aqueous phase which is usually present in a thickened state. Preferred emulsifiers are O / W emulsifiers, such as polyglycerol esters, sorbitan esters or partially esterified glycerides.

0073According to a further preferred embodiment, the agents according to the invention are a shower gel, a shampoo formulation or a bath preparation.

0074Such formulations contain at least one active ingredient according to the invention and usually anionic surfactants as base surfactants and amphoteric and / or nonionic surfactants as cosurfactants. Further suitable active substances and / or auxiliary substances are generally selected from lipids, perfume oils, dyes, organic acids, preservatives and antioxidants as well as thickeners / gelling agents, skin conditioners and humectants.

0075These formulations contain in particular 2 to 50% by weight, such as 5 to 40% by weight, or 8 to 30% by weight of surfactants, based on the total weight of the formulation.

0076All anionic, neutral, amphoteric or cationic surfactants commonly used in personal cleansing agents can be used in the washing, showering and bathing preparations.

0077Suitable anionic surfactants are, for example, alkyl sulfates, alkyl ether sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl succinates, alkyl sulfosuccinates, N-alkoylsarcosinates, acyl taurates, acyl isothionates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, alpha-olefin sulfonates, especially alkali metal sulfonates, in particular alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal alkali metal sulfates As sodium, potassium, magnesium, calcium, and ammonium and triethanolamine salts. The alkyl ether sulfates, alkyl ether phosphates and alkyl ether carboxylates can have between 1 and 10 ethylene oxide or propylene oxide units, preferably 1 to 3 ethylene oxide units, in the molecule.

0078These include e.g. B. sodium lauryl sulfate, ammonium tauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl ether sulfate, sodium lauryl sarcosinate, sodium oleyl succinate, ammonium umlauryl sulfosuccinate, sodium dodecylbenzenesulfonate, triethanolamine dodecylbenzenesulfonate.

0079Suitable amphoteric surfactants are e.g. B. alkylbetaines, alkylamidopropylbetaines, alkylsulfobetaines, alkylglycinates, alkylcarboxyglycinates, alkylamphoacetates or propionates, alkylamphodiacetates or dipropionates.

0080For example, cocodimethylsulfopropylbetaine, laurylbetaine, cocamidopropylbetaine or sodium cocamphopropionate can be used.

0081Examples of suitable nonionic surfactants are the reaction products of aliphatic alcohols or alkylphenols with 6 to 20 carbon atoms in the alkyl chain, which can be linear or branched, with ethylene oxide and / or propylene oxide. The amount of alkylene oxide is about 6 to 60 moles per mole of alcohol. Alkylamine oxides, mono- or dialkylalkanolamides, fatty acid esters of polyethylene glycols, ethoxylated fatty acid amides, alkylpolyglycosides or sorbitan ether esters are also suitable.

0082In addition, the washing, showering and bathing preparations can contain conventional cationic surfactants, such as. B. quaternary ammonium compounds, for example cetyltrimethylammonium chloride.

0083Furthermore, the shower gel / shampoo formulations thickeners such. B. table salt, PEG-55, propylene glycol oleate, PEG-120-methylglucose dioleate and others as well as preservatives, other active ingredients and auxiliaries and water.

ii) Special designs for hair application products

0084According to a further preferred embodiment, the agents according to the invention are a hair treatment agent.

0085Hair treatment compositions according to the invention contain in particular at least one active ingredient according to the invention in an amount in the range from about 0.0001 to 50% by weight, such as 0.001 to 10% by weight, in particular 0.005 to 0.1% by weight, based on the total weight of the agent.

0086The hair treatment compositions according to the invention are preferably in the form of a foaming agent, hair mousse, hair gel, shampoos, hair sprays, hair foam, lace fluids, leveling agents for perms, hair dye and bleach or "hot oil treatments". Depending on the area of ​​application, the hair cosmetic preparations can be applied as (aerosol) spray, (aerosol) foam, gel, gel spray, cream, lotion or wax. Hair sprays include both aerosol sprays and pump sprays without propellant. Hair foams include both aerosol foams and pump foams without propellant. Hair sprays and hair foams preferably comprise predominantly or exclusively water-soluble or water-dispersible components. If the compounds used in the hair sprays and hair foams according to the invention are water-dispersible, they can be used in the form of aqueous microdispersions with particle diameters of usually 1 to 350 nm, preferably 1 to 250 nm. The solids contents of these preparations are usually in a range from about 0.5 to 20% by weight. These microdispersions generally do not require any emulsifiers or surfactants to stabilize them.

0087In a special embodiment, the hair cosmetic formulations according to the invention contain a) 0.0001 to 50% by weight or 0.001 to 10, or 0.005 to 1% by weight of at least one active ingredient according to the invention b) 20 to 99.95% by weight of water and / or alcohol, c) 0 to 50% by weight of at least one propellant gas, d) 0 to 5% by weight of at least one emulsifier, e) 0 to 3% by weight of at least one thickener, and up to 25% by weight % other ingredients.

0088Alcohol is to be understood as all alcohols customary in cosmetics, e.g. B. ethanol, isopropanol, n-propanol.

0089Furthermore, this includes all styling and conditioner polymers known in cosmetics, which can be used in combination with the active compounds according to the invention if very special properties are to be set.

0090Suitable conventional hair cosmetic polymers are, for example, the aforementioned cationic, anionic, neutral, nonionic and amphoteric polymers, to which reference is made here.

0091To adjust certain properties, the preparations can also contain conditioning substances based on silicone compounds. Suitable silicone compounds are, for example, polyalkylsiloxanes, polyarylsiloxanes, polyarylalkylsiloxanes, polyether siloxanes, silicone resins or dimethicone copolyols (CTFA) and amino-functional silicone compounds such as amodimethicones (CTFA).

0092The polymers according to the invention are particularly suitable as setting agents in hair styling preparations, in particular hair sprays (aerosol sprays and pump sprays without propellant gas) and hair foams (aerosol foams and pump foams without propellant gas).

0093In a preferred embodiment, spray preparations contain a) 0.0001 to 50% by weight or 0.001 to 10, or 0.005 to 1% by weight of at least one active ingredient according to the invention, b) 20 to 99.9% by weight of water and / or Alcohol, c) 0 to 70% by weight of at least one blowing agent, d) 0 to 20% by weight of further constituents.

0094Blowing agents are the blowing agents commonly used for hair sprays or aerosol foams. Mixtures of propane / butane, pentane, dimethyl ether, 1,1-difluoroethane (HFC-152 a), carbon dioxide, nitrogen or compressed air are preferred.

0095A formulation according to the invention for aerosol hair foams contains a) 0.0001 to 50% by weight or 0.001 to 10, or 0.005 to 1% by weight of at least one active ingredient according to the invention, b) 55 to 99.8% by weight of water and / or alcohol, c) 5 to 20% by weight of a blowing agent, d) 0.1 to 5% by weight of an emulsifier, e) 0 to 10% by weight of further constituents.

0096All emulsifiers customarily used in hair foams can be used as emulsifiers. Suitable emulsifiers can be nonionic, cationic or anionic or amphoteric.

0097Examples of nonionic emulsifiers (INCI nomenclature) are Laurethe, e.g. B. Laureth-4; Cetethe, e.g. B. Cetheth-1, polyethylene glycol cetyl ether, cetearethe, e.g. B. Cetheareth-25, polyglycol fatty acid glycerides, hydroxylated lecithin, lactyl esters of fatty acids, alkyl polyglycosides.

0098Examples of cationic emulsifiers are cetyldimethyl-2-hydroxyethylammonium dihydrogen phosphate, cetyltrimonium chloride, cetyltrimmonium bromide, cocotrimonium methyl sulfate, quaternium-1 to x (INCI).

0099Anionic emulsifiers can be selected, for example, from the group of alkyl sulfates, alkyl ether sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl succinates, alkyl sulfosuccinates, N-alkoyl sarcosinates, acyl taurates, acyl isethionates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, in particular alkali metal alkali metal sulfates, for example alkali metal alkali metal sulfate, alpha-alkali metal alkali metal sulfate, Potassium, magnesium, calcium, as well as ammonium and triethanolamine salts. The alkyl ether sulfates, alkyl ether phosphates and alkyl ether carboxylates can have between 1 and 10 ethylene oxide or propylene oxide units, preferably 1 to 3 ethylene oxide units, in the molecule.

0100A preparation suitable according to the invention for styling gels can be composed, for example, as follows: a) 0.0001 to 50% by weight or 0.001 to 10, or 0.005 to 1% by weight of at least one active ingredient according to the invention b) 80 to 99.85 % By weight of water and / or alcohol, c) 0 to 3% by weight, preferably 0.05 to 2% by weight, of a gel former, d) 0 to 20% by weight of further constituents.

0101The use of gel formers can be advantageous in order to set special rheological or other application properties of the gels. All gel formers customary in cosmetics can be used as gel formers. These include slightly cross-linked polyacrylic acid, for example carbomer (INCI), cellulose derivatives, e.g. B. hydroxypropyl cellulose, hydroxyethyl cellulose, cationically modified celluloses, polysaccharides, e.g. B. Xanthan gum, capryl / caprin triglyceride, sodium acrylate copolymers, Polyquaternium-32 (and) Paraffinum Liquidum (INCI), sodium acrylate copolymers (and) Paraffinum Liquidum (and) PPG-1 Trideceth-6, acrylamidopropyltrimonium chloride / acrylamide copolymers, steareth- 10-allyl ether, acrylate copolymers, Polyquaternium-37 (and) Paraffinum Liquidum (and) PPG-1 Trideceth-6, Polyquaternium 37 (and) Propylene Glycol Dicaprate Dicaprylate (and) PPG-1 Trideceth-6, Polyquaternium-7, Polyquaternium-44.

0102Special shampoo formulations contain a) 0.0001 to 50% by weight or 0.001 to 10, or 0.005 to 1% by weight of at least one active ingredient according to the invention, b) 25 to 94.95% by weight of water, c) 5 to 50 % By weight of surfactants, c) 0 to 5% by weight of a further conditioning agent, d) 0 to 10% by weight of further cosmetic ingredients.

0103All anionic, neutral, amphoteric or cationic surfactants commonly used in shampoos can be used in the shampoo formulations.

0104Suitable anionic surfactants are, for example, alkyl sulfates, alkyl ether sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl succinates, alkyl sulfosuccinates, N-alkoylsarcosinates, acyl taurates, acyl isothionates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, alpha-olefin sulfonates, especially alkali metal sulfonates, in particular alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal sulfonates, especially alkali metal alkali metal sulfates As sodium, potassium, magnesium, calcium, and ammonium and triethanolamine salts. The alkyl ether sulfates, alkyl ether phosphates and alkyl ether carboxylates can have between 1 and 10 ethylene oxide or propylene oxide units, preferably 1 to 3 ethylene oxide units, in the molecule.

0105For example, sodium lauryl sulfate, ammonium laurysulfate, sodium lauryl ether sulfate, ammonium lauryl ether sulfate, sodium lauroyl sarcosinate, sodium oleyl succinate, ammonium lauryl sulfosuccinate, sodium dodecyl benzene sulfonate, triethanolamine dodecyl benzene sulfonate are suitable.

0106Suitable amphoteric surfactants are, for example, alkylbetaines, alkylamidopropylbetaines, alkylsulfobetaines, alkylglycinates, alkylcarboxyglycinates, alkylamphoacetates or propionates, alkylamphodiacetates or dipropionates.

0107For example, cocodimethylsulfopropylbetaine, laurylbetaine, cocamidopropylbetaine or sodium cocamphopropionate can be used.

0108Examples of suitable nonionic surfactants are the reaction products of aliphatic alcohols or alkylphenols with 6 to 20 carbon atoms in the alkyl chain, which can be linear or branched, with ethylene oxide and / or propylene oxide. The amount of alkylene oxide is about 6 to 60 moles per mole of alcohol. Alkylamine oxides, mono- or dialkylalkanolamides, fatty acid esters of polyethylene glycols, alkylpolyglycosides or sorbitan ether esters are also suitable.

0109In addition, the shampoo formulations can contain conventional cationic surfactants, such as. B. quaternary ammonium compounds, for example cetyltrimethylammonium chloride.

0110In the shampoo formulations, customary conditioning agents can be used in combination with the active compounds according to the invention to achieve certain effects.

0111These include, for example, the aforementioned cationic polymers with the designation Polyquaternium according to INCI, in particular copolymers made from vinylpyrrolidone / N-vinylimidazolium salts (Luviquat FC, Luviquat HM, Luviquat MS, Luviquat Care), copolymers made from N-vinylpyrrolidone / dimethylaminoethyl methacrylate (quaternized with quaternized) D PQ 11), copolymers of N-vinylcaprolactam / N-vinylpyrrolidone / N-vinylimidazolium salts (Luviquat D Hold), cationic cellulose derivatives (Polyquaternium-4 and -10), acrylamide copolymers (Polyquaternium-7). Protein hydrolyzates and conditioning substances based on silicone compounds, for example polyalkylsiloxanes, polyarylsiloxanes, polyarylalkylsiloxanes, polyether siloxanes or silicone resins, can also be used. Other suitable silicone compounds are dimethicone copolyols (CTFA) and amino-functional silicone compounds such as amodimethicone (CTFA). Cationic guar derivatives such as guar hydroxypropyltrimonium chloride (INCI) can also be used.

4.3 Cooling oral care products

0112Oral care products according to the invention can be formulated in a manner known per se, for example as toothpaste, tooth gel, or aqueous or aqueous-alcoholic oral care products (mouthwash).

0113Oral care compositions according to the invention contain, based on the weight of the composition, 0.00001 to 50% by weight, 0.0001 to 10% by weight, 0.001 to 5% by weight, 0.005 to 1% by weight or 0.1 up to 20% by weight, 0.5 to 15% by weight or 1 to 5% by weight of the total amount of at least one active ingredient according to the invention

0114In addition, the oral care products, in particular toothpastes, can also contain abrasives, such as silicon oxide hydrate, dicalcium phosphate dihydrate, calcium carbonate, sodium hydrogen carbonate, calcium pyrophosphate and aluminum oxide. For example, a mixture of precipitated silicon which tends to be viscous and abrasive precipitated silicon [<nplcit id="ncit0025" npl-type="b"><text>Handbook of Pharmaceutical Excipients, The Pharmaceutical Society of Great Britain, 1 Lambeth High Street, London SE 1 7JN, England, pages 253-256</text></nplcit>] be used. The former is used because of its thixotropic properties, the latter because of its better effectiveness in removing the substances adhering to the tooth surfaces. The use of these products ensures a low abrasion effect, because they are amorphous solids of medium hardness, which at the same time are fully compatible with the fluoride used as a mineralizing agent because they do not contain lime salts, which would make them insoluble and reduce their bioavailability.

0115The formulation of the oral care products according to the invention, such as toothpaste, can also contain suitable additives and vehicles in order to improve their properties and to facilitate their production. These are, for example selected from binders, thickeners, fragrances, dyes, preservatives, wetting agents or humectants, surfactants, lubricants, opacifiers, remineralizing agents, surfactants, buffers, alcohols, vitamins, water, additional active ingredients and mixtures thereof.

0116Any agent normally used in the preparation of this type of recipe can be used as the binder, e.g. B. tragacanth. The binder can be contained in the formulation in an amount of 0.5-1.5% by weight of the total amount.

0117Organic thickeners such as sodium carboxymethyl cellulose, cellulose ether, xanthan gum, carageenans, sodium alginate and carbopole can also be incorporated into the oral care product. Inorganic thickeners such as silica thickeners, sodium aluminum silicates and clays can also be used to provide the appropriate rheology. The thickener can be contained in the formulation in an amount of 0.5-5% by weight of the total amount.

0118The toothpaste can be added by adding a suitable conventional fragrance, e.g. B. a peppermint flavor. Essential oils including clove oil, cinnamon oil, peppermint oil and spearmint oil are also suitable. The fragrance can be contained in the recipe in an amount of 0.5-15% by weight of the total amount.

0119Any of the dyes normally used in the production of toothpaste can be used as the dye, for example brilliant blue FCF, C.42090 [KIRSCH PHARMA]. The dye can be contained in the formulation in an amount of 0.001-0.005% by weight of the total amount.

0120The preservative can be any conventional means such as a derivative of benzoic acid e.g. B. act p-hydroxy methyl benzoate. The preservative can be contained in the formulation in an amount of 0.1-0.3% by weight of the total amount.

0121As a sweetener you can e.g. B. sodium saccharin or cyclamic acid and their derivatives, e.g. B. use sodium cyclamate. The sweetener can be contained in the formulation in an amount of 0.08-0.15% by weight of the total amount.

0122The wetting or moisturizing agent used to prevent the toothpaste from drying out and hardening is selected in particular from glycerol, sorbitol, propylene glycol, xylitol and liquid polyethylene glycols, in particular a mixture of sorbitol, glycerol and xylitol, for example in a proportion of 1-60% by weight. -% of the total.

0123A lubricant can be any of the agents commonly used in the formulation of a toothpaste, e.g. B. dimethicone (polymer of dimethylpolysiloxane), which is a surface-active agent that helps to give the toothpaste of the invention good rheological properties. The lubricant can be contained in the formulation in an amount of 0.25 to 0.75% by weight of the total amount.

0124Any of the commonly used agents can be used as opacifiers, e.g. B. Titanium dioxide. The opacifier can be contained in the formulation in an amount of 0.05 to 1% by weight of the total amount.

0125A fluoride source, e.g. As sodium fluoride, tin (II) fluoride and sodium monofluorophosphate, because in this way 100% of an active fluoride as a remineralization agent for the white lesions caused by the organic acids, which are a result of the bacterial metabolism. The remineralizing agent can be contained in the formulation in an amount of 0.2 to 0.4% by weight of the total amount.

0126Typically, conventional ingredients can also be present, such as anionic surfactants, such as sodium lauryl sulphate, sodium N-lauryl sarcosinate, sodium lauryl sulphoacetate and sodium alkylglyceryl ether sulphonate. The surfactant can be contained in the formulation in an amount of 0.05 to 5% by weight of the total amount

0127If desired, the toothpaste proposed by the invention may also contain vitamin selected from the group consisting of vitamin A, vitamin B5, vitamin C and vitamin E and mixtures thereof. In the case of use, each vitamin can be contained in the formulation in an amount of 0.1 to 5% by weight of the total amount. These vitamins can be used as such, in the form of provitamins or in the form of acceptable pharmaceutical salts. Vitamin A, which is usually used in the form of its palmitate salt, promotes epithelization of the oral mucosa and protects the gums. Vitamin B5, more precisely D-panthenol, has an analgesic, healing and anti-inflammatory effect, protects the epithelial mucosa, promotes the epithelialization of injuries and smoothes the scars; it is suitable for the treatment of injuries resulting from tooth extractions, gingivitis, stomatitis, pain after the insertion of dentures, ulcers, traumatic mucosal injuries, chronic and recurrent aphthae. Vitamin C regenerates the epithelium of the oral mucosa, promotes collagen synthesis and the immune system (inflammation mechanism) and increases the protective capacity of the phagocytes against bacteria. The vitamin E, which is usually used in the form of its acetate salt, has an analgesic and anti-inflammatory effect, protects the oral mucosa against fat overoxidation due to the formation of free radicals and against contaminating substances in the environment (ozone, cigarette smoke, etc.) and promotes healing of the injuries. By adding one or some of these vitamins, the invention provides a toothpaste which, in addition to the aforementioned properties, also has anti-inflammatory properties and analgesic effects, which increase the protective capacity of the membranes of the oral mucosa and reduce the index of plaque and tartar formation and that of bacterial contamination .

0128Additional active ingredients are, for example, antimicrobial and plaque-penetrating agents, such as beta-naphthol, thymol, chlorothymol and hexylresorcinol; or germicidal compounds such as quaternary ammonium compounds .; Tartar control agents such as tetrasodium pyrophosphate, GANTREZ-Polymer® S-70, sodium tripolyphosphate and zinc citrate; Peroxide compounds such as hydrogen peroxide and inorganic peroxides.

0129Optionally, a buffer can also be used, such as alkali metal phosphate buffer, which is contained in concentrations suitable for maintaining a pH of about 6-8. The presence of potassium ions also has a hypersensitive effect.

0130Water or alcohol can be present in a proportion of 1 to 20% by weight of the total amount of the agent.

0131In combination with the alcohol or instead of the alcohol, glycol compounds such as glycerin, sorbitol or propylene glycol can also be used.

0132The oral care product according to the invention can easily be produced by mixing suitable amounts of the various components in a reactor equipped, for example, with stirrer blades.

4.4. Cooling plasters

0133In principle, the active ingredient content can vary over a wide range, for example 0.00001 to 50% by weight, in particular 0.001 to 10% by weight or 0.005 to 1% by weight.

0134Patches according to the invention can be constructed in any way, for example according to the matrix system, the membrane system or the fleece system (<nplcit id="ncit0026" npl-type="s"><text>Drug Dev. Ind. Pharm. 14 (1988), 183-209</text></nplcit>; <nplcit id="ncit0027" npl-type="s"><text>Drug Dev. Ind. Pharm. 13: 589-651 (1987)</text></nplcit>;<nplcit id="ncit0028" npl-type="s"><text> Drugs of Today 23: 625-646 (1987)</text></nplcit>.

0135The matrix system consists of 3 parts in the simplest way: the flexible support film, the adhesive matrix containing the active ingredient and a release film. If a non-adhesive matrix is ​​used, an edge zone of the support film must be provided with adhesive to adhere to the skin.

0136A membrane system, on the other hand, has at least 5 parts: a flexible support film, a reservoir with dissolved or suspended active substance, a membrane for controlling the release of the active substance, an adhesive layer applied to the membrane and a release film.

0137In the nonwoven system, the layer containing the active ingredient consists of an absorbent nonwoven or porous polymer which is impregnated with an active ingredient solution or suspension. This layer, which is firmly connected to the support film, is covered by a release film. The edge of the support film is provided with adhesive for application to the skin.

0138In principle, all active ingredients according to the invention can be formulated in this way.

0139The auxiliaries to be used are the usual ones for the production of plasters. In addition to the adhesive agent, usually a polymer with a glass transition temperature between -70 and -10, in particular -55 and -25 ° C, and a backing film which is coated with this adhesive agent, and the active ingredient are often emulsifiers, thickeners and Substances that are supposed to influence the release of the active ingredient and other auxiliaries are added.

0140The sticky polymers with the above-mentioned low glass temperatures are known, for example from <patcit id="pcit0042" dnum="US2973282A"><text>U.S. Patents 2,973,282</text></patcit> and <patcit id="pcit0043" dnum="US3307544A"><text>3 307 544</text></patcit>. The self-adhesive tapes and foils should stick to human skin on mere contact, but the cohesion of the adhesive layer and its adhesion to the carrier foil should be greater than the adhesion to the skin, so that they can be removed again largely without residue. These are generally copolymers based on acrylic and methacrylic esters of alcohols with 2 to 12, in particular 4 to 8, carbon atoms, which can contain numerous other comonomers in copolymerized form, for example (meth) acrylic acid, (meth) acrylonitrile, (meth ) acrylamide, N-tert-butyl- (meth-) acrylamide, vinyl esters such as vinyl acetate, propionate or butyrate, other vinyl compounds such as styrene, furthermore butadiene. Butyl acrylate and 2-ethylhexyl acrylate are particularly noteworthy. The polymers can be crosslinked by adding small amounts of comonomer with 2 or more copolymerizable double bonds, for example diacrylates such as butanediol diacrylate or divinyl compounds such as divinylbenzene, or by adding other crosslinking agents, for example melamine-formaldehyde resins. Polyisobutylenes and polyvinyl ethers of different molecular weights can also be used as sticky polymers.

0141The particle size of the dispersions should be between 50 and 500 nm, in particular between 50 and 200 nm. The particle size and the degree of crosslinking can be adjusted in a known manner depending on the polymerization conditions and the comonomers. Smaller particle sizes and an increased degree of crosslinking can cause an increase in the active ingredient release.

0142Matrix plasters can be produced in the usual way by dissolving or finely dispersing the active ingredient in a suitable polymer solution and then pulling this self-adhesive composition containing the active ingredient into a film by means of roller or knife application processes. In some cases, it is expedient to dissolve or finely disperse the active ingredient in an organic solvent, for example ethanol or acetone, before adding it to the polymer solution. This enables a better distribution of the active ingredient in the polymer.

0143The patches can also be made after the German patent application <patcit id="pcit0044" dnum="DEP3807283"><text>P 38 07 283.1</text></patcit> are prepared by incorporating the active ingredient in fine powder form (particle size below 200, in particular below 50 μm) in the aqueous latex dispersion, or dispersing or dissolving in an aqueous emulsifier solution and mixing this aqueous latex dispersion at a temperature of 10 to 80, in particular 30 admixed up to 70 ° C. In addition, the salt of an active ingredient in aqueous solution can be mixed with the polymer dispersion at a pH at which the active ingredient is predominantly in the water-soluble ionized form. The active ingredient is then brought into the uncharged, water-insoluble form by pH shifting and simultaneously emulsified into the dispersion.

0144Advantageously, the active ingredient is introduced, the emulsifier and water are added, and the mixture is then mixed with the polymer dispersion. The resulting active ingredient-containing dispersion is optionally provided with further auxiliaries and, as mentioned, drawn out and dried in a manner known per se on a support film to form a film. The drying temperature can be between room temperature and 100 ° C, with an optimum between the desired rapid drying and the formation of bubbles to be avoided in the film and the thermal stress on the active ingredient generally at 35 to 45 ° C.

0145This process has the great advantage of avoiding organic solvents. In principle, however, all other usual manufacturing methods for matrix plasters can also be considered.

0146The resulting films have thicknesses of 10 to 800, preferably 50 to 300 microns. The film can be produced continuously or discontinuously. The application process can be repeated several times until the film has reached the desired thickness. The sticky polymer layer contains the active ingredient in a concentration in the range from 1 to 40, in particular 5 to 25,% by weight. The same concentration also applies to the reservoir liquid in the membrane system and to the active ingredient solution or dispersion with which the nonwoven or the porous polymer is impregnated in the nonwoven system.

0147The surfactants customary for this purpose are used as emulsifiers for both the active compounds and the polymers, such as the sodium salt of longer-chain fatty acids and the sulfuric acid half-ester of an (optionally ethoxylated) fatty alcohol as examples of anionic surfactants as well as polyoxethylated alkylphenols and longer-chain fatty alcohols (eg hexadecane (l) -ol) and glycerol fatty acid partial esters as examples of nonionic surfactants and co-emulsifiers.

0148The desired viscosity of the ready-to-extract mass can be adjusted, for example, with polyacrylic acids or cellulose derivatives.

0149Melamine-formaldehyde resins, for example, can be used as additional crosslinking agents which improve the cohesion and thus the adhesive properties of the films.

0150Swelling substances such as polyvinylpyrrolidone, cellulose derivatives or polyacrylates act to improve the release of the active substance, since the film can absorb more water and the resistance to diffusion thereby decreases. The release of the active ingredients can also be improved by the addition of hydrophilic plasticizers such as glycerol, 1,2-propanediol of the polyethylene glycols and lipophilic plasticizers such as triacetin, dibutyl phthalate or isopropyl myristate.

0151Matrix patches usually result in first-order drug release. The use of fillers which adsorb the active ingredient, such as Aerosil, microcrystalline cellulose or lactose, results in approximately zero-order release.

0152The support film onto which the self-adhesive composition containing the active ingredient is dried is expediently practically impermeable both for the active ingredient and for water vapor. It can consist, for example, of an aluminum-plastic composite film, a metallized plastic film, a plastic film which is provided with a barrier layer of, for example, polyvinylidene chloride on the active ingredient side, or of a simple plastic film, for example polyester film.

0153The plasters according to the invention, which are constructed according to the membrane system, are also produced in the usual way (for example <patcit id="pcit0045" dnum="EP0186071A2"><text>EP 0 186 071 A2</text></patcit>, <patcit id="pcit0046" dnum="US4262003A"><text>US 4,262,003</text></patcit>).

0154The plasters constructed according to the fleece system are produced by soaking fleece or porous polymers attached to the support film with a solution or dispersion of the active ingredient in a hydrophilic or lipophilic solvent or solvent mixture. The impermeable release liner is then applied.

4.5 Cooling foods

0155Cooling foods according to the invention can be in solid, liquid, semi-solid, pasty, creamy or foamed form (at ambient temperature). In addition to conventional food ingredients, they contain at least an effective (ie, a cooling) amount of at least one active ingredient according to the invention.

0156Typical components are fats, carbohydrates, proteins, fiber, water, alcohol and the like.

0157The protein content can be, for example, 0 to 50% by weight, based on the total weight of the food; the fat content can be, for example, 0 to 50% by weight, based on the total weight of the food; the carbohydrate content can be, for example, 0 to 90% by weight, based on the total weight of the food; the fiber content can be, for example, 0 to 90% by weight, based on the total weight of the food; the water content can, for example 0 up to 95% by weight, based on the total weight of the food; the alcohol content can be, for example, 0 to 15% by weight, based on the total weight of the food; the proportion of active ingredients according to the invention can be, for example, in the range from 0.0001 to 50, 0.001 to 20, 0.005 to 1, or 0.01 to 10, in particular 0.1 to 10 or 1 to 5% by weight, based on the total weight of the Food.

0158Examples of carbohydrates are, for example, mono- and disaccharides, glucose, galactose, mannose, lactose, maltose and sucrose; Fructose and mannose; Polysaccharides such as B. Strengths. Maltodextrins, flour.

0159The term "fiber" refers to soluble, insoluble, fermentable, non-fermentable, or any combination of such fiber. The fiber can e.g. B. soy fibers, pectin, certain resistant starches, oligofructose, inulins, oat fibers, pea fibers, guar gum, gum acazia, modified cellulose.

0160The fat component can be any lipid or fat, the suitability of which is known for use in nutrients. Typical fats include milk fat, safflower oil, canola oil, egg yolk lipid, olive oil, cottonseed oil, coconut oil, palm oil, palm kernel oil, soybean oil, sunflower oil, fish oil and fractions of all the above oils, such as palmolein, medium-chain triglycerides (MCT), and fatty acid esters , where it is in the fatty acids z. B. arachidonic acid, linoleic acid, palmitic acid, stearic acid, docosahexaenoic acid, eicosapentaenoic acid, linolenic acid, oleic acid, lauric acid, capric acid, caprylic acid, caproic acid. High oleic forms of various oils are also considered suitable for the present use, such as high oleic sunflower oil and high oleic safflower oil.

0161The protein can be any protein and / or amino acid mixture whose suitability for use in nutrients is known. Typical proteins are animal proteins, vegetable proteins such as soy protein, milk protein such as skimmed milk protein, whey protein and casein, and amino acids (or salts thereof) such as isoleucine, phenylalanine, leucine, lysine, methionine, threonine, tryptophan, arginine, glutamine, taurine, valine. Preferred protein sources are whey protein, sodium caseinate or calcium caseinate, which may be mixed with amino acids. For some applications, a preferred protein source is hydrolyzed protein (protein hydrolyzate) that may have amino acids added to it.

0162The protein hydrolyzate can be any suitable protein hydrolyzate used in a nutrient, such as soy protein hydrolyzate, casein hydrolyzate, whey protein hydrolyzate, other animal and vegetable protein hydrolyzates, and mixtures thereof. The protein hydrolyzate of the composition according to the invention is preferably a soy protein, whey protein or a casein protein hydrolyzate, which comprises short peptides and amino acids and is optionally mixed with additional amino acids. In a preferred embodiment, the protein hydrolyzate suitable according to the invention contains a high proportion of free amino acids (for example more than 40%) and low molecular weight peptide fragments.

0163The hydrolyzed protein of the composition of the invention is also preferably mixed with various free amino acids to provide a nutritionally balanced amino acid content. Examples of such free amino acids include L-tryptophan, L-methionine, L-cystine, L-tyrosine and L-arginine.

0164The nutrients according to the invention optionally also contain vitamins and minerals. The person skilled in the art is familiar with the fact that minimum requirements for certain vitamins and minerals have been set up which are necessary for normal physiological function. Those skilled in the art also know that adequate additional amounts of vitamin and mineral components must be added to the nutrients to compensate for certain losses in the processing and storage of such compositions. The composition according to the invention optionally contains nutritionally significant amounts of vitamins and minerals.

0165Examples of minerals, vitamins and other nutrients that may be present in the composition according to the invention include vitamin A, vitamin B.₆, Vitamin B₁₂, Vitamin E, Vitamin K, Vitamin C, Vitamin D, inositol, taurine, folic acid, thiamine, riboflavin, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium , Sodium, beta-carotene, nucleotides, selenium, chromium, molybdenum and L-carnitine. Minerals are usually added in salt form.

0166The composition according to the invention optionally also usually contains emulsifiers and / or stabilizers such as lecithin (e.g. from egg or soy), modified lecithin (e.g. enzymatically or acetylated), carrageenan, xanthan gum, mono- and diglycerides, guar gum, carboxymethyl cellulose, Stearoyl lactylates, succinylated monoglycerides, sucrose esters of fatty acids, diacetyl tartaric esters of monoglycerides, polyglycerol esters of fatty acids or any mixtures thereof.

0167The composition according to the invention optionally contains one or more natural or artificial flavor carriers to improve the palatability. Any flavor carrier used in the sector can be used, such as strawberry, cherry, chocolate, orange, coconut, vanilla; Spices such as nutmeg and cinnamon; or citric acid. In some cases where natural flavor carriers such as coconut pieces are used, the ingredient contributes to the overall nutritional profile of the composition, ie it contributes to the quality and quantity of the fat, protein and / or carbohydrate ingredient.

0168The composition according to the invention optionally also contains various other constituents which can contribute to the nutritional profile of the composition and / or impart desired taste properties, such as taste enhancement or mouthfeel. Such ingredients include peanuts, raisins, cheese powder, vinegar, salt, sodium bicarbonate. For bars, the composition is usually covered with a chocolate or flavored coating (e.g. Chocolate, vanilla, strawberry, etc.).

0169The composition according to the invention optionally also contains natural or artificial dyes in order to improve the aesthetic appeal.

0170The compositions of the invention may exist in several physical forms, e.g. B. as a liquid enteral nutrient or beverage for adults or children, in a semi-solid form such as pudding, cream, mousse, or a solid form such as a nutritional bar or biscuit.

0171The composition according to the invention can be produced by known standard processes in food technology, for example by processes analogous to those described in the following publications: <patcit id="pcit0047" dnum="US4670268A"><text>U.S. Patents 4,670,268</text></patcit>; <patcit id="pcit0048" dnum="US4497800A"><text>4,497,800</text></patcit>; <patcit id="pcit0049" dnum="US4900566A"><text>4,900,566</text></patcit>; <patcit id="pcit0050" dnum="US5104677A"><text>5,104,677</text></patcit>; <patcit id="pcit0051" dnum="US5389395A"><text>5,389,395</text></patcit>; and<patcit id="pcit0052" dnum="US5223285A"><text>5,223,285</text></patcit>; <nplcit id="ncit0029" npl-type="b"><text>Chocolate, Cocoa and Confectionery: Science and Technology, 3rd edition, Bernard W. Minifie, Van Nostrand Reinhold, New York, 1989, pp. 502-506</text></nplcit>; which is referred to in full.

0172In the case of nutritional bars and cookies, the aim is usually to bake the composition after the physical shaping.

0173If desired, the composition according to the invention can be sterilized by known methods, for example by heat treatment such as autoclaving or sterilizing or radiation, or can be produced and packaged using sterile methods.

0174The composition according to the invention can be packaged in any type of container or packaging whose suitability for storing food is known, such as paper, glass, coated cardboard, plastic or coated metal cans.

0175The composition according to the invention can be nutritionally balanced. The term "nutritionally balanced" means that the composition contains adequate nutrients to maintain a healthy human life over extended periods of time.

4.6. Textile products equipped with active ingredients according to the invention.

0176In principle, the active ingredient content can vary over a wide range, for example 0.00001 to 50% by weight, in particular 0.001 to 10% by weight or 0.005 to 1% by weight.

0177The finishing of textiles with active ingredients according to the invention is of interest in many ways.

0178For example, the finishing of textiles with cooling compounds is used where clothing can come into direct contact with the skin so that the active ingredient can exert its effects, for example locally or systemically, through transdermal transmission. Recently, textiles have been reported that are equipped with so-called wellness additives, ie substances that promote well-being (<nplcit id="ncit0030" npl-type="s"><text>R. Breier "Megatrend Wellness - Innovative Ideas for Textile Equipment", 31st Aachen Textile Days November 2004</text></nplcit>).

0179An insecticidal finish, on the other hand, is of interest in terms of material protection, for example finishing the textile against moth damage, etc., but in particular also for repelling parasitic insects, such as mosquitoes.

0180A fundamental problem in the finishing of textiles with active substances is the binding of the active substance to the textile carrier, which on the one hand has to ensure the durability of the finishing and on the other hand has to be chosen so that the active substance does not lose its effectiveness. Various approaches are proposed for this in the prior art.

0181For example, cyclodextrins have been proposed for binding active ingredients to textiles (see for example <patcit id="pcit0053" dnum="DE19810951A"><text>DE-A-19810951</text></patcit> and <patcit id="pcit0054" dnum="EP0392608A"><text>EP-A-0 392 608</text></patcit>). Cyclodextrins are cyclic oligosaccharides that are formed by the enzymatic breakdown of starch. The most common cyclodextrins are α-, β- and γ-cyclodextrins, which consist of six, seven and eight α-1,4-linked glucose units, respectively. A characteristic feature of the cyclodextrin molecules is their ring structure with largely unchangeable dimensions. The inner diameter of the rings is about 570 pm for α-cyclodextrin, about 780 pm for β-cyclodextrin and about 950 pm for γ-cyclodextrin. Due to their structure, cyclodextrins are able to include guest molecules, in particular hydrophobic guest molecules, in varying amounts until they are saturated.

0182The <patcit id="pcit0055" dnum="EP1710345A"><text>EP-A-1710345</text></patcit> describes the finishing of textiles with fragrances and other low molecular weight organic active substances via an amylose-containing substance with an amylose content of at least 30% bound to the textile.

0183The amylose content of the amylose-containing substance binds the active ingredient to the textile and releases it in a controlled manner so that the effect is retained over a long period of time. It is believed that the active substance, similar to cyclodextrins, is reversibly bound in the cavities formed by the helical conformation of the amylose in the sense of an inclusion compound, which on the one hand fixes the active substance on the surface of the textile support and on the other hand enables controlled release .

0184In addition to amylose, all substances, in particular amylose-containing starches, ie native starches, modified starches and starch derivatives, whose amylose content is at least 30% by weight and in particular at least 40% by weight are suitable for the finishing of textiles according to the invention. The starch can be native, for example corn starch, wheat starch, potato starch, sorghum starch, rice starch or maranta starch, obtained by partial digestion of native starch or chemically modified. Pure amylose as such is also suitable, for example enzymatically obtained amylose, e.g. B. from sucrose amylose. Mixtures of amylose and starch are also suitable, provided the total amylose content is at least 30% by weight, based on the total weight of the mixture. It goes without saying that here and below, all data in% by weight which relate to amylose or substances containing amylose, in the case of mixtures of amylose and starch, are always based on the total weight of amylose + starch, unless expressly stated otherwise.

0185Particularly suitable according to the invention are amylose-containing substances, in particular amylose and amylose-containing starches, and amylose / starch mixtures, the amylose content of which is at least 40% by weight and in particular at least 45% by weight, based on the total weight of the substance. As a rule, the amylose content will not exceed 90% by weight and in particular 80% by weight. Such substances are known and commercially available. For example, amylose-containing starches are sold by Cerestar under the trademark Amylogel® and National Starch under the trade names HYLON® V and VII.

0186To achieve the binding of the active substance (s) to the textile, the textile with the amylose-containing substance can generally be used in an amount of at least 0.5% by weight, preferably at least 1% by weight and in particular at least 2 Equip% by weight, based on the weight of the textile. As a rule, the amylose-containing substance will be used in an amount of not more than 25% by weight, frequently not more than 20% by weight and in particular not more than 15% by weight, based on the weight of the textile not to adversely affect the tactile properties of the textile.

0187First, the textile material is finished with the amylose-containing substance as such and then the finished textile is treated with a suitable preparation of the active ingredient. As a result, the amylose-containing substance on the textile material is loaded with the active ingredient.

0188But you can also use the amylose-containing substance together with an active ingredient to finish the textile. Here, the active ingredient and the amylose-containing substance can be used both as a mixture of separate components and in the already prefabricated form of the amylose-active ingredient complex.

0189As a rule, the active ingredient will be used in an amount sufficient for the desired effect. The upper limit is determined by the maximum absorption capacity of the amylose units of the amylose-containing substance used and will generally not exceed 20% by weight and often 10% by weight, based on the amylose content of the substance. If desired, the active ingredient is generally used in an amount of 0.00001 to 15% by weight, 0.0001 to 10% by weight, 0.001 to 5% by weight, 0.005 to 1% by weight or 0.1 to 10% by weight or 0.5 to 5% by weight, based on the amylose content of the amylose-containing substance.

0190Combinations of active ingredients according to the invention with other active ingredients known per se and suitable for textile finishing can also be used for textile finishing.

0191In principle, all organic compounds and mixtures of organic compounds which are known as active substances and which induce a physiological effect in living beings such as humans and animals, including microorganisms, are suitable as further active substances. Active substances that are known to form inclusion compounds with cyclodextrins are to be mentioned. Active substances which have hydrocarbon groups and in particular aliphatic, cycloaliphatic and / or aromatic structures are particularly suitable. The molecular weight of the active ingredients is typically below 1000 daltons and often in the range from 100 to 600 daltons. Also suitable are inorganic compounds such as hydrogen peroxide, which are known to be bound in cyclodextrins (see here<nplcit id="ncit0031" npl-type="b"><text>F. Vögtle, Supramolecular Chemistry, 2nd edition, BG Teubner, Stuttgart 1992</text></nplcit>, Cyclodextrins and literature cited there)

0192Other active ingredients include, in particular, pharmaceutical active ingredients and active ingredients which promote the well-being of living beings, in particular humans, and which are also commonly referred to as "wellness additives". In contrast to pharmaceutical active ingredients, wellness additives do not necessarily have to have a therapeutic effect.

0193Rather, the wellbeing effect can be based on a variety of factors such as caring, stimulating, cosmetic or other effects. Organic active substances which act against parasitic organisms are equally suitable. These include, for example, active substances which act against fungi and / or microorganisms, for example fungicides and bactericides, or which act against animal pests such as snails, worms, mites, insects and / or rodents, for example Nematicides, molluscicides, insecticides, acaricides, rodenticides and repellent active ingredients, and furthermore active ingredients against grass, ie herbicides, or fragrances.

0194Preferred active pharmaceutical ingredients are those which are known to be absorbed through the skin. These include, for example, ibuprofen, flurbiprofen, acetylsalicylic acid, acetamidophen, apomorphine, butylated hydroxytoluene, chamzulen, gujazulene, chlorthalidone, cholecalciferol, dicumarol, digoxin, diphenylhydantoin, furosemide, hydroflumethacid, iodotinolinidinidinidotinidinidotin, dinotinotinidinidotin, dinotininotinidinidotin, dinotininotinidinidotin, iomotinolinidotin, iodinolinotinidotin, iodinolotinidol Papaverine alkaloids such as papaverine, laudanosine, ethaverine and narcotin as well as berberine, further retionol, trans-retinoic acid, pretinol, spironolactone, Sulpirid, theophylline, theobromine, corticosteroids and derivatives such as testosterone, 17-methyltestosterone, cortisone, corticosterone, dexamethasone, triamcinolone, methylprednisolone, fludrocortisone, fluocortolone, prednisone, prednisolone, progesterone, among others estrogenstradiol, and gestagenethers, such as estrogenstradiol and gestagenethers, such as estrogenstradiol, and gestagenoltradiol , Norethisterone and ethisterone, as well as phenethylamine and derivatives such as tyramine, adrenaline, noradrenaline and dopamine.

0195Examples of active substances suitable according to the invention with an action against parasitic organisms are the below <u>www.reith-pfister.de/w.list.html</u> as well as under <u>www.hclrss.demon.co.uk/class pesticides.html</u> called nematicides, bactericides, fungicides, insecticides, insect repellents, acaricides and molluscicides.

0196Examples of bactericidal and fungicidal substances include:<ul id="ul0016" list-style="dash" compact="compact"><li>Antibiotics, for example cycloheximide, griseofulvin, kasugamycin, natamycin, polyoxin, streptomycin, penicillin or gentamycin;</li><li>Organic compounds and complexes of biocidal metals, e.g. complexes of silver, copper, tin and / or zinc such as bis (tributyl tin) oxide, copper, zinc and tin naphthenates, oxine copper such as Cu-8, Tris-N- ( cyclohexyldiazeniumdioxy) aluminum, N- (cyclohexyldiazeniumdioxy) tributyltin, bis-N- (cyclohexyldiazeniumdioxy) copper ;;</li><li>Quaternary ammonium salts, e.g. benzyl-C₈-C₁₈-alkyldimethylammonium halides, especially chlorides (benzalkonium chlorides);</li><li>aliphatic nitrogen fungicides and bactericides such as cymoxanil, dodin, dodicin, guazidine, iminoctadine, dodemorph, fenpropimorph, fenpropidin, tridemorph,</li><li>Substances with peroxide groups such as hydrogen peroxide, and organic peroxides such as dibenzoyl perodide;</li><li>Organic chlorine compounds such as B. chlorhexidine;</li><li>Triazole fungicides such as azaconazole, cyproconazole, diclobutrazole, difenoconazole, diniconazole, epoxiconazo, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, metconazole, propiconazole, tetraconazole and tebuconazole, tebuconazole;</li><li>Strobilurins such as dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin and trifloxystrobin</li><li>Sulfonamides such as tolylfluanid and diclofluanid;</li><li>Iodine compounds such as diiodomethyl-p-tolyl sulfone, napcocide 3-iodine-2-propynyl alcohol, 4-chlorophenyl-3-iodopropargyl formal, 3-bromo-2,3-diiodo-3-propenylethyl carbonate, 2,3,3-triiodallyl alcohol, 3-iodine -2-propynyl-n-hexyl carbamate, 3-bromo-2,3-diiodo-2-propenyl alcohol, 3-iodo-2-propynylphenyl carbamate, 3-iodo-2-propynyl-n-butyl carbamate, O-1- (6- Iodine-3-oxohex-5-ynyl) phenyl carbamate, O-1- (6-iodine-3-oxohex-5-ynyl) butyl carbamate;</li><li>Isothiazolinones such as N-methylisothiazolin-3-one, 5-chloro-N-methylisothiazolin-3-one, 4,5-dichloro-N-octylisothiazolin-3-one, 1,2-benzisothiazol-3 (2H) on, 4, 5-trimethylisothiazol-3-one and N-octyl-isothiazolin-3-one.</li></ul>

0197Examples of insecticides and acaricides are<ul id="ul0017" list-style="dash" compact="compact"><li>Organophosphates such as Acephate, Azamethiphos, Azinphos-methyl, Chlorpyrifos, Chlorpyriphos-methyl, Chlorfenvinphos, Diazinon, Dichlorvos, Dicrotophos, Dimethoate, Disulfoton, Ethion, Fenitrothion, Fenthion, Isoxathion, Malathion, Methamidophosevinosophin, Parath Oxydemeton-methyl, Paraoxon, Parathion, Phenthoate, Phosalone, Phosmet, Phosphamidon, Phorate, Phoxim, Pirimiphos-methyl, Profenofos, Prothiofos, Sulprophos, Triazophos, Trichlorfon;</li><li>in particular pyrethroids such as acrinatrin, allethrin, bioallethrin, barthrin, bifenthrin, bioethanomethrin, cyclethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, cypermethrinhrin, -Cypermethrin, Cyphenothrin, Deltamethrin, Dimefluthrin, Dimethrin, Empenthrin, Fenfluthrin, Fenprithrin, Fenpropathrin, Fenvalerat, Esfenvalerat, Flucythrinat, Fluvinate, tau-Fluvinate, Furethrin, Permethrin, Biopermethrin, trans-permethrin, phenothrin, prallethrin, profluthrin, pyresmethrin, resmethrin, bioresmethrin, cismethrin, tefluthrin, terallethrin, tetramethrin, tralomethrin, transfluthrin, etofenprox, silfenffen, flufxprox, flufenprox.</li><li>Pyrrole and pyrazole insecticides such as acetoprole, ethiprole, fipronil, tebufenpyrad, tolfenpyrad, chlorfenapyr and vaniliprole.</li></ul>

0198Examples of repellent active ingredients are, in particular, anthraquinone, acridine bases, copper naphthenate, butopyronoxyl, dibutyl phthalate, dimethyl phthalate, dimethyl carbate, ethohexadiol, hexamides, methoquine butyl, N-methylneodecanamide, camphor, bergamot oil, pyrethrum, especially clove oil, geranium oil, geranium oil, geranium oil m-toluamide and 1-piperidinecarboxylic acid 2- (2-hydroxyethyl) -1-methylpropyl ester (Picardin).

0199Examples of wellness additives are, in particular, the substances and substance mixtures listed below, for example<ul id="ul0018" list-style="dash" compact="compact"><li>Fats, preferably of vegetable origin, for example lecithins,</li><li>Vegetable oils such as jojoba oil, tea tree oil, clove oil, evening primrose oil, almond oil, coconut oil, avocado oil, soybean oil and the like,</li><li>Fatty acids, for example ω-6 fatty acids, linolenic acid, linoleic acid,</li><li>Waxes of animal or vegetable origin such as beeswax, candelilla wax, shea butter, shore butter, mango kernel butter, japan wax and the like,</li><li>Vitamins, especially fat-soluble vitamins, e.g. B. tocopherols, vitamin E, vitamin A and the like,</li><li>Cortico steroids such as cortisone, corticosterone, dexamethasone, triamcinolone, methylprednisolone, fludrocortisone, fluocortolone, prednisone, prednisolone, progesterone,</li><li>Amino acids, e.g. arginine, methionine,</li><li>Plant extracts such as algae extract, horse chestnut extract, mango extract and the like.</li></ul>

0200To improve the washing permanence of the equipment according to the invention, it has proven useful to fix the amylose-containing substance on the textile with a binder. Suitable binders are, on the one hand, film-forming, water-insoluble polymers and, on the other hand, low-molecular-weight reactive substances that polymerize when heated. As a rule, the binder will be used in an amount such that the weight ratio of amylose-containing substance to water-insoluble polymer is in the range from 1: 1 to 100: 1, preferably in the range from 1.5: 1 to 50: 1 and in particular in the range from 2: 1 to 20: 1.

0201As a rule, the film-forming polymers are used in the form of an aqueous dispersion of finely divided polymer particles. The particle size is of secondary importance for the success according to the invention. However, it is usually below 5 µm (weight average) and is usually 50 nm to 2 µm.

0202The film-forming polymer can in particular have a glass transition temperature T_G in the range of -40 to 100 ° C, preferably -30 to +60 ° C, in particular -20 to +40 ° C. If the polymeric binder comprises several polymer components, at least the main component should have a glass transition temperature in this range. In particular, the glass transition temperature of the main constituent is in the range from -30 ° C to +60 ° C and particularly preferably in the range from -20 ° C to +40 ° C. All polymeric components preferably have a glass transition temperature in these ranges. The glass transition temperatures given relate to the "midpoint temperature" determined according to ASTM-D 3418-82 by means of DSC. In the case of crosslinkable binders, the glass transition temperature relates to the uncrosslinked state.

0203Examples of suitable film-forming polymers are based on the following polymer classes:<ol id="ol0006" compact="compact"><li>(1) polyurethane resins</li><li>(2) acrylate resins (pure acrylates: copolymers of alkyl acrylates and alkyl methacrylates);</li><li>(3) styrene acrylates (copolymers of styrene and alkyl acrylates);</li><li>(4) styrene / butadiene copolymers;</li><li>(5) polyvinyl esters, especially polyvinyl acetates and copolymers of vinyl acetate with vinyl propionate;</li><li>(6) vinyl ester-olefin copolymers, e.g. B. vinyl acetate / ethylene copolymers;</li><li>(7) vinyl ester-acrylate copolymers, e.g. B. vinyl acetate / alkyl acrylate copolymers and vinyl acetate / alkyl acrylate / ethylene terpolymers;</li></ol>

0204Such polymers are known and commercially available, e.g. B. Polymers of classes (2) to (7) in the form of aqueous dispersions under the names ACRONAL, STYROFAN, BUTOFAN (BASF-AG), MOWILITH, MOWIPLUS, APPRETAN (Clariant), VINNAPAS, VINNOL (WACKER). Aqueous polyurethane dispersions (1) which are suitable for the process according to the invention are, in particular, those which are used for the coating of textiles (see e.g.<nplcit id="ncit0032" npl-type="s"><text>BJ Hemmrich, Int. Text. Bull. 39, 1993, No. 2, pp. 53-56</text></nplcit>; "<nplcit id="ncit0033" npl-type="s"><text>Aqueous polyurethane coating systems "Chemical fibers / textile. 39 91 (1989) T149, T150</text></nplcit>; <nplcit id="ncit0034" npl-type="s"><text>W. Schröer, Textilveredelung 22, 1987, pp. 459-467</text></nplcit>). Aqueous polyurethane dispersions are commercially available, e.g. B. under the trade names Alberdingk® from Alberdingk, Impranil® from BAYER AG, Permutex® from Stahl, Waalwijk, Netherlands, from BASF SE or can be produced by known processes, such as those described in "<nplcit id="ncit0035" npl-type="b"><text>Manufacturing process for polyurethanes "in Houben-Weyl," Methods of Organic Chemistry ", Volume E 20</text></nplcit>/<nplcit id="ncit0036" npl-type="s"><text>Macromolecular substances, p. 1587</text></nplcit>, <nplcit id="ncit0037" npl-type="s"><text>D. Dietrich et al., Angew. Chem. 82 (1970), p. 53 ff.</text></nplcit>, <nplcit id="ncit0038" npl-type="s"><text>Appl. Macrom. Chem. 76, 1972, 85 ff.</text></nplcit> and <nplcit id="ncit0039" npl-type="s"><text>Appl. Macrom. Chem. 98, 1981, 133-165</text></nplcit>, <nplcit id="ncit0040" npl-type="s"><text>Progress in Organic Coatings, 9, 1981, pp. 281-240</text></nplcit>, respectively. <nplcit id="ncit0041" npl-type="b"><text>Römpp chemistry lexicon, 9th edition, volume 5, p. 3575 </text></nplcit>to be discribed.

0205The film-forming polymers can be self-crosslinking, ie the polymers have functional groups (crosslinkable groups) which, when the composition dries, if necessary when heated, react with one another, with the functional groups of amylose or with a low molecular weight crosslinker to form bonds.

0206Examples of crosslinkable functional groups include aliphatically bound OH groups, NH-CH₂-OH groups, carboxylate groups, anhydride groups, blocked isocyanate groups and amino groups. A polymer is often used which still has free OH groups as reactive groups. As a rule, the proportion of reactive functional groups is 0.1 to 3 mol / kg polymer. The crosslinking can be effected within the polymer by reaction of complementarily reactive functional groups. The polymer is preferably crosslinked by adding a crosslinker which has reactive groups which are complementary in their reactivity to the functional groups of the crosslinker. Suitable pairs of functional groups which have a complementary reactivity are known to the person skilled in the art. Examples of such pairs are OH / COOH, OH / NCO, NH₂/ COOH, NH₂/ NCO and M²⁺/ COOH, where M²⁺ for a divalent metal ion such as Zn²⁺, Approx²⁺, or Mg²⁺ stands. Examples of suitable crosslinkers are the diols or polyols mentioned below for the polyurethanes; primary or secondary diamines, preferably primary diamines, e.g. B. Alkylene diamines such as hexamethylene diamine, diethylene triamine, triethylene tetramine, tetraethylene pentamine, N, N-bis [(aminopropyl) amino] ethane, 3,6-dioxaoctanediamine, 3,7-dioxanone diamine, 3,6,9-trioxaundecanediamine or Jeffamine, (4,4 '-Diaminodicyclohexyl) methane, (4,4'-diamino-3,3-dimethyldicyclohexyl) methane; Amino alcohols such as ethanolamine, hydroxypropylamine; ethoxylated di- and oligoamines; Dihydrazides of aliphatic or aromatic dicarboxylic acids such as adipic acid dihydrazide; Dialdehydes such as glyoxal; partially or completely O-methylated melamines, as well as compounds or oligomers, the average of two or more, preferably three or more isocyanate groups or reversible z. B. hydrogen sulfite blocked isocyanate groups. In this case, the quantitative ratio of crosslinker to polymeric binder is such that the molar ratio of the reactive groups in the polymeric binder (total amount of reactive groups in the polymers) to the reactive groups in the crosslinker is generally in the range from 1:10 to 10: 1 and preferably in the range from 3: 1 to 1: 3. The weight ratio of polymeric binder (calculated as a solid) to crosslinking agent is usually in the range from 100: 1 to 1: 1 and in particular in the range from 50: 1 to 5: 1.

0207As an alternative to fixing the amylose-containing substance with water-insoluble polymers, the amylose or the amylose-containing substance can also be reacted with reactive compounds which have at least one group which is reactive towards the OH groups of the amylose and at least one further functional group which is opposite the functional groups the fibers of the textile material, for example OH groups, NH₂-Groups or COOH groups, reactive, fix on the textile material. The reactive compounds include the above-mentioned crosslinkers and those in<patcit id="pcit0056" dnum="DE4035378A"><text>DE-A 40 35 378</text></patcit> substances proposed for fixing cyclodextrins, for example N-hydroxymethyl and N-alkoxymethyl derivatives of urea or urea-like compounds such as dimethylolurea (bis (hydroxymethyl) urea), di (methoxymethyl) urea, dimethylolalkanediol diurethanes such as N, N-dimethylolethylene urea (N, N- Bis (hydroxymethyl) imidazolin-2-one), N, N-dimethylol-dihydroxyethylene urea (N, N-bis (hydroxymethyl) -4,5-dihydroxyimidazolin-2-one), dimethylolpropylene urea and the like. Such materials are commercially available in the form of aqueous formulations for finishing textiles, for example under the trade names Fixapret® and Fixapret®-eco from BASF SE. The reactive materials that can be used to fix the amylose-containing substance on the textile material include, in particular, compounds with 2, 3, 4 or more (optionally reversibly blocked) isocyanate groups, especially those with bisulfite or CH-acidic compounds or Oximes, e.g. Butanone oxime reversibly blocked polyisocyanate prepolymers based on polyether and polyester urethanes, which in <patcit id="pcit0057" dnum="DE2837851"><text>DE 2837851</text></patcit>, <patcit id="pcit0058" dnum="DE19919816"><text>DE 19919816</text></patcit> and the older European patent application <patcit id="pcit0059" dnum="EP03015121A"><text>03015121</text></patcit> to be discribed. Products of this type are also commercially available, for example under the trade names PROTOLAN®367 and PROTOLAN®357 from Rotta GmbH, Mannheim.

0208To fix the amylose-containing substance, the procedure known for fixing cyclodextrins can also be used in an analogous manner, in which the cyclodextrin or, in the present case, the amylose-containing substance is provided with reactive anchors, for example by dicarboxylic acids or dicarboxylic acid anhydrides such as maleic acid and fumaric acid , Maleic anhydride, succinic acid, succinic anhydride or adipic acid, with diisocyanates, e.g. B. Toluene diisocyanate, isophorone diisocyanate, tetramethylene diisocyanate or hexamethylene diisocyanate, or with aminocarboxylic acids in a manner known per se in such a way that only one of the functionalities present in these compounds reacts with the OH groups of the amylose-containing substance and the other is retained for binding to the reactive groups of the fiber material . Reactive anchors can also be generated on the amylose-containing substance by reaction with 1,3,5-trichlorotriazine, 2,3-dichloroquinoxaline-5,6-carboxylic acid chloride and with chlorodifluoropyrimidine.

0209Furthermore, alkoxysilanes such as diethoxydimethylsilane, dimethoxydimethylsilane, triethoxyphenylsilane, tetraethoxysilane and dimeric, trimeric and higher condensation products of these compounds can also be used to fix the amylose.

0210In this way, basically all textile materials can be equipped, ie non-made goods as well as made goods. Here and below, textile materials include woven fabrics, knitted fabrics, knitted fabrics and nonwovens. The textile materials can be constructed from natural fiber yarns, synthetic fiber yarns and / or mixed yarns. In principle, all fiber materials usually used for the production of textiles can be considered as fiber materials. These include cotton, wool, hemp fiber, sisal fibers, flax, ramie, polyacrylonitrile fibers, polyester fibers, polyamide fibers, viscose fibers, silk, acetate fibers, triacetate fibers, aramid fibers and the like as well as mixtures of these fiber materials.

0211The finishing or treatment of the textile materials with the amylose-containing substance can be carried out in a manner known per se, for example by means of the <patcit id="pcit0060" dnum="DE4035378A"><text>DE-A 4035378</text></patcit> described for the finishing of textiles with cyclodextrins.

0212Examples include processes in which the amylose-containing substance, optionally as a complex with the active ingredient, has already been spun into the fiber, the filament and / or the yarn from which the fabric is made.

0213Often, however, the textile material will be treated with the amylose-containing substance or a complex of amylose-containing substance and active ingredient before or after assembly. As a rule, the textile will be treated with an aqueous liquor which contains the amylose-containing substance and, if necessary, the active substance in sufficient quantity. Depending on the type of application and the desired amount in which the amylose-containing substance is to be applied, the concentration of amylose-containing substance in the liquor is in the range from 1 to 40% by weight, in particular in the range from 2 to 20% by weight. and especially in the range of 4 to 15% by weight.

0214The type of treatment is of minor importance and can be carried out, for example, as a minimum order, for example by spray application, as a normal order in the padder or as a high-moisture order. The textile material is soaked with the aqueous liquor. If necessary, excess liquor can then be removed, for example by squeezing to a liquor intake of about 30 to 120%.

0215Another option for treating the textile with an amylose-containing substance or a complex of amylose-containing substance and active ingredient is to use a liquor containing water in which the desired amount of amylose-containing substance and optionally active ingredient is contained, for example 0.5 to 20% by weight. (based on the mass of the textile to be finished). The textile material is treated for a certain period of time, e.g. 10-60 min, with the treatment liquor in suitable equipment (e.g. Reel runner; Roller skid; Paddle; etc.) soaked and then squeezed and / or spun off as indicated above. The liquor ratio is usually in the range from 1: 2 to 1:50 and in particular in the range from 1: 3 to 1:20.

0216Such methods are known to the person skilled in the art, for example from <nplcit id="ncit0042" npl-type="b"><text>HK Rouette, Lexicon of textile finishing, Laumann-Verlag, Dülmen 1995, p. 669 ff</text></nplcit>.

0217As a rule, the treatment with the liquor is followed by a drying process. The temperatures are generally in the range from 100 to 200 ° C. and preferably in the range from 120 to 180 ° C. Drying can be carried out in the devices customary for this purpose, in the case of finished goods, for example by tumbling dry at the temperatures indicated above. In the case of non-assembled goods, the textile material will usually be guided over one or more stenter frames following the order.

0218If the amylose-containing substance is used together with a film-forming polymer, the drying leads to the amylose-containing substance being fixed on the textile fibers. As a rule, the drying temperature will not fall below 100 and is preferably in the range from 120 to 200 ° C. and in particular in the range from 140 to 180 ° C. In general, drying takes place over a period of 1 to 10 minutes, in particular 1 to 2 minutes, with longer drying times also being suitable.

0219For treatment with an aqueous liquor, it has proven to be advantageous if, in addition to the amylose-containing substance and optionally the active ingredient, the aqueous liquor contains at least one surface-active substance (or surface-active substance) which is used to disperse the amylose-containing substance and the active ingredient in the aqueous Fleet is suitable. The surface-active substance is preferably an oligomeric or polymeric dispersant. In contrast to low molecular weight surface-active substances, the term oligomeric or polymeric dispersant includes those dispersants whose number-average molecular weight is generally at least 2000 daltons, for example 2000 to about 100000 daltons and in particular in the range from about 3000 to 70,000 daltons.

0220As a rule, the aqueous liquor contains the polymeric or oligomeric dispersant in an amount of 0.5 to 20% by weight, preferably 1 to 18% by weight and in particular 5 to 15% by weight, based on the amylose-containing substance.

0221Suitable oligomeric or polymeric dispersants are water soluble and include both neutral and amphoteric water soluble polymers as well as cationic and anionic polymers, the latter being preferred.

0222Examples of neutral polymeric dispersants are polyethylene oxide, ethylene oxide / propylene oxide copolymers, preferably block copolymers, polyvinylpyrrolidone and copolymers of vinyl acetate with vinylpyrrolidone.

0223The preferred anionic oligomeric or polymeric dispersants are distinguished by the fact that they have carboxyl groups and / or sulfonic acid groups and are usually used as salts, for example as alkali metal salts or ammonium salts.

0224Preferred anionic dispersants are, for example, carboxylated derivatives of cellulose such as carboxymethyl cellulose, homopolymers of ethylenically unsaturated C.₃-C₈-Mono- and C₄-C₈Dicarboxylic acids, for example acrylic acid, methacrylic acid, maleic acid, itaconic acid, copolymers of at least two different ethylenically unsaturated C.₃-C₈-Mono- and C₄-C₈Dicarboxylic acids as mentioned above, and copolymers of at least one of the aforementioned ethylenically unsaturated C.₃-C₈-Mono- or C₄-C₈Dicarboxylic acid with at least one neutral comonomer. Examples of neutral comonomers are N-vinyl lactams such as N-vinyl pyrrolidone, vinyl esters of aliphatic C.₂-C₁₆-Carboxylic acids such as vinyl acetate, vinyl propionate, amides of the aforementioned ethylenically unsaturated carboxylic acids, such as acrylamide, methacrylamide and the like, hydroxy-C₁-C₄alkyl (meth) acrylates such as hydroxyethyl acrylate and methacrylate, esters of ethylenically unsaturated C.₃-C₈-Mono- or C₄-C₈Dicarboxylic acids with polyethers, for example esters of acrylic acid or methacrylic acid with polyethylene oxides or ethylene oxide / propylene oxide block copolymers, vinyl aromatics such as styrene and C.₂-C₁₆Olefins such as ethylene, propene, 1-hexene, 1-octene, 1-decene, 1-dodecene and the like. Also preferred are homopolymers of ethylenically unsaturated sulfonic acids such as styrene sulfonic acid and acrylamidopropane sulfonic acid and their copolymer with the aforementioned comonomers. The proportion of the ethylenically unsaturated acid in the copolymers will generally be at least 20% by weight and not exceed a value of 90% by weight and in particular 80% by weight, in each case based on the total weight of all monomers constituting the polymer .

0225Copolymers of at least one of the abovementioned acids and at least one comonomer are known and commercially available for this purpose, for example the copolymers of acrylic acid and maleic acid as Sokalan brands from BASF AG.

0226Also preferred anionic dispersants are phenolsulfonic acid-formaldehyde condensates and naphthalenesulfonic acid-formaldehyde condensates (for example the Tamol and Setamol brands from BASF) and ligninsulfonates.

0227Dispersants which can also be used are low molecular weight anionic, nonionic, cationic, ampholytic and zwitterionic surfactants. Suitable surfactants are, for example, the alkali metal, ammonium or amine salts of C₈-C₁₈Alkyl sulfates, such as sodium lauryl sulfate; C.₈-C₁₈Alkyl sulfonates such as dodecyl sulfonate; C.₈-C₁₈Alkyl ether sulfates; as well as C₈-C₁₈Alkyl ethoxylates; Polyoxyethylene sorbitan esters; C.₈-C₁₈Alkylglycinates; C.₈-C₁₈-Alkyldimethylamine oxides; Betaines etc. The alkyl sulfates and alkyl sulfonates are preferred.

0228If the amylose-containing substance is not used together with a film-forming, water-insoluble polymer, the textile can be treated with the polymer in a separate working step. In particular, the treatment is carried out together with the amylose-containing substance. Accordingly, a particular embodiment relates to a method in which the aqueous liquor additionally comprises a dispersed, film-forming, water-insoluble polymer of the type described above. The amount of film-forming polymer is chosen such that the weight ratio of amylose-containing substance to water-insoluble polymer is in the range from 1: 1 to 100: 1, preferably in the range from 1.5: 1 to 50: 1 and in particular in the range from 2: 1 to 20: 1.

0229The finishing of the textile with the active ingredient can take place in a separate process or in one work step together with the finishing with the amylose-containing substance.

0230If the textile is finished with the active substance in a separate operation, the textile will expediently also be treated with an aqueous liquor of the active substance. For this purpose, the active ingredient, which is usually insoluble in water, will generally be emulsified or dispersed in water, if appropriate using suitable surface-active substances. Suitable surface-active substances are, in particular, the aforementioned low molecular weight surfactants and among these preferably the nonionic surfactants, in particular polyoxyethylene sorbitan esters, esters of mono- or oligosaccharides with C.₆-C₁₈Fatty acids and particularly preferred C₈-C₁₈Alkyl ethoxylates, especially those with a degree of ethoxylation in the range from 6 to 50. As a rule, the aqueous liquor contains the active ingredient in an amount of 0.1 to 10% by weight and in particular in an amount of 0.2 to 5% by weight. -%. The amount of surface-active substance is generally in the range from 0.5 to 50% by weight and in particular in the range from 3 to 30% by weight, based on the active ingredient. The active ingredient can be applied from an aqueous liquor using the customary methods, for example by means of a padder.

0231But you can also carry out the treatment with active ingredient and amylose-containing substance in one operation. In principle, one can proceed as described for the amylose-containing substance, the aqueous liquor of the amylose-containing substance now additionally containing the at least one active ingredient. The active ingredient can be added separately to the liquor or in the form of an inclusion compound, ie in the form of a host-guest complex with the amylose-containing substance.

0232The method according to the invention can be used to finish any textiles, including fabrics, knitted fabrics, nonwovens and the like. The type of textile material depends primarily on the desired application.

0233The textiles to be finished can be ready-made products such as clothing, including underwear and outerwear, such as shirts, pants, jackets, outdoor, trekking and military equipment, roofs, tents, nets, e.g. insect nets and curtains, hand and bath towels , Bedding and the like.

0234In the same way, the raw material can be finished in bale or roll form.

0235The textiles finished with active substances against parasitic organisms such as insects and acarids are, in addition to protecting human beings, also particularly suitable in animal protection for protection against ticks, mites, fleas and the like.

0236The textile materials can be constructed from natural fiber yarns, synthetic fiber yarns and / or blended yarns, the fabrics usually having a weight per unit area in the range from 10 to 500 g / m 2² preferably 20 to 250 g / m² exhibit. In principle, all fiber materials usually used for the production of textiles can be considered as fiber materials. These include cotton, wool, hemp fiber, sisal fibers, flax, ramie, polyacrylonitrile fibers, polyester fibers, polyamide fibers, viscose fibers, silk, acetate fibers, triacetate fibers, aramid fibers and the like as well as mixtures of these fiber materials. Also suitable are glass fibers and mixtures of the aforementioned fiber materials with glass fibers such. B. Glass fiber / Kevlar blends.

0237With an amylose-based active ingredient finish described above, the active ingredients remain in the textiles treated therewith even after several washes. In addition, the textiles finished in this way are distinguished by a pleasant grip, which is particularly advantageous for the comfort of clothing made from these textiles.

4.7 Cooling tobacco products

0238In principle, the active substance content can vary over a wide range, for example 0.00001 to 50 % by weight, in particular 0.001 to 10% by weight or 0.005 to 1% by weight.

0239The active compounds according to the invention can also advantageously be used for the production of tobacco products. Examples of such tobacco products include cigars, cigarettes, pipe tobacco, chewing tobacco, and snuff.

0240The production of tobacco products, which are supplemented with cooling additives, is known per se and is described, for example, in <patcit id="pcit0061" dnum="US3111127A"><text>US 3,111,127</text></patcit>, <patcit id="pcit0062" dnum="US5752529A"><text>US 5,752,529</text></patcit> and <patcit id="pcit0063" dnum="US20050000529A"><text>US 2005/0000529</text></patcit>, to which express reference is hereby made.

4.8 Cooling packaging materials

0241The active compounds according to the invention are also advantageously suitable for the production of packaging materials.

0242Production is also carried out in a manner known per se. The active ingredients can be incorporated into the packaging material, in free or, for example, encapsulated form, or applied to the packaging material in free or encapsulated form.

0243Appropriately equipped plastic packaging materials can be manufactured according to the information in the literature on the production of polymer films (e.g. <nplcit id="ncit0043" npl-type="b"><text>Ullmann, 6th Edn, 2003. Vol. 36, p. 567</text></nplcit>). The production of papers coated in a suitable manner is also known and is described, for example, in<nplcit id="ncit0044" npl-type="b"><text>Ullmann, Vol. 25, pp. 106 ff, 6th Edn, 2003</text></nplcit>.

5. Active ingredient combinations

0244If appropriate, the compounds (cooling agents) of structure types 1, 2 and 3 according to the invention can be combined with other known active ingredients, in particular also those having a comparable effect. For example, these can be combined with known cooling compounds, such as Menthol, menthone, N-ethyl-p-menthancarboxamide (WS-3, also called menthan-3-carboxylic acid-N-ethylamide), N-2,3-trimethyl-2-isopropylbutanamide (WS-23), menthyl lactate (Frescolat® ML), menthone glycerol acetal (Frescolat® MGA), mono-menthyl succinate (Physcool®), mono-menthyl glutarate, O-menthyl glycerin, menthyl-N, N-dimethylsuccinamate.

0245The cooling active substances according to the invention, in particular those in Table 0 (see below) can preferably be combined with the following cooling active substances: menthol and menthol derivatives (for example L-menthol, D-menthol, racemic menthol, isomenthol, neoisomenthol, neomenthol), menthyl ether (for example (I- Menthoxy) -1,2-propanediol, (I-menthoxy) -2-methyl-1,2-propanediol, I-menthyl methyl ether), menthyl esters (e.g. Menthyl formate, menthyl acetate, menthyl isobutyrate, menthyl lactate, L-menthyl L-lactate, L-menthyl D-lactate, menthyl (2-methoxy) acetate, menthyl (2-methoxyethoxy) acetate, menthyl pyroglutamate glycol, menthyl carbonate (e.g. menthyl carbonate) Menthyl ethylene glycol carbonate, menthyl glycerol carbonate or their mixtures), the half esters of menthol with a dicarboxylic acid or its derivatives (e.g. Mono-menthyl succinate, mono-menthyl glutarate, mono-menthyl malonate, O-menthyl succinate ester-N, N- (dimethyl) amide, O-menthyl succinate ester amide), mentha carboxamides (e.g. mentha carboxylic acid N-ethyl amide [WS3], Na- (glycine methane) ], Menthone carboxylic acid N- (4-cyanophenyl) amide, menthone carboxylic acid N- (alkoxyalkyl) amide), menthone and menthone derivatives (e.g. L-menthone glycerol ketal), 2,3-dimethyl-2- (2-propyl) butanoic acid derivatives (e.g. 2,3-Dimethyl-2- (2-propyl) -butanoic acid-N-methylamide [WS23]), isopulegol or its esters (I - (-) - isopulegol, I - (-) - isopulegol acetate), menthand derivatives (e.g. p -Menthan-3,8-diol), Cubebol or synthetic or natural mixtures containing Cubebol, pyrrolidone derivatives of cycloalkyldione derivatives (eg 3-methyl-2 (1-pyrrolidinyl) -2-cyclopenten-1-one) or tetrahydropyrimidin-2-one (e.g. Icilin or related compounds, as in <patcit id="pcit0064" dnum="WO2004026840A"><text>WO 2004/026840</text></patcit> described).

0246The cooling active substances according to the invention, in particular those in Table 0 (see below), can particularly preferably be combined with the following cooling active substances: menthyl ether (for example (I-menthoxy) -1,2-propanediol, (I-menthoxy) -2-methyl-1 , 2-propanediol), more polar menthyl esters (e.g. menthyl lactate, L-menthyl L-lactate, L-menthyl D-lactate, menthyl (2-methoxy) acetate, menthyl (2-methoxyethoxy) acetate, menthyl pyroglutamate), menthyl carbonates (e.g. Menthyl propylene glycol carbonate, menthyl ethylene glycol carbonate, menthyl glycerol carbonate), the half-esters of menthol with a dicarboxylic acid or its derivatives (e.g. mono-menthyl succinate, mono-menthyl glutarate, mono-menthyl malonate, O-menthyl succinate ester-N, non-dimethyl amide), non-, dimethyl amide menthane carboxamides according to the invention (e.g. Menthone carboxylic acid N-ethylamide [WS3], Na (menthyl carbonyl) glycine ethyl ester [WS5], Menthone carboxylic acid N- (4-cyanophenyl) amide, menthone carboxylic acid N- (alkoxyalkyl) amide), menthone derivatives (e.g. L-menthone glycerol ketal), 2, 3-dimethyl-2- (2-propyl) -butanoic acid derivatives (e.g. 2,3-dimethyl-2- (2-propyl) -butanoic acid-N-methylamide), pyrrolidone derivatives of cycloalkyldione derivatives (e.g. 3-methyl-2 (1-pyrrolidinyl ) -2-cyclopenten-1-one) or tetrahydropyrimidin-2-one (e.g. Icilin or related compounds, which in <patcit id="pcit0065" dnum="WO2004026840A"><text>WO 2004/026840</text></patcit> are described).

0247The statements mentioned in the entire chapter 4 and 5 also apply to the special part of the invention (chapter 6) unless otherwise stated.

6. Special part of the invention

0248As already indicated above, the special part of the invention relates to the use of very special compounds (TRPM8 receptor modulators) for producing a long-lasting physiological cooling effect on the skin or mucous membrane.

0249The special part of the invention further relates to mixtures and preparations (compositions) comprising specific such compounds.

0250It also relates to a method for producing a medicament and a method for achieving a physiological cooling effect on the skin and / or mucous membranes, in each case using particularly suitable compounds.

0251Physiological cooling agents are used regularly to produce a cool sensory impression on the skin or mucous membrane, for example on the mucous membrane in the mouth, nose and / or throat, although there is actually no physical cooling, such as when solvents evaporate . Both individual components and mixtures can be used as physiological cooling agents. It should be noted that not all connections <i>in vitro</i> Receptors that are involved in the mediation of a physiological cooling effect actually influence such an effect <i>in vivo</i> on the skin or on mucous membranes. In particular, such an effect will not always be identical. This means, for example, that the strength of the mediated physiological cooling effect and the course of the strength of the cooling effect against time cannot be deduced solely from the fact that a specific compound is an argonist of a receptor involved in imparting a cooling impression.

0252The best-known physiologically active cooling agent is L-menthol, but it has some disadvantages, e.g. B. strong smell impression, high volatility and in higher concentrations a bitter and / or pungent taste, or a skin irritant effect.

0253For this reason, strong cooling agents that do not have the disadvantageous properties of I-menthol have previously been sought. For example, lactic acid esters of menthol (s) were produced in accordance with<patcit id="pcit0066" dnum="DE2608226"><text>DE 2 608 226</text></patcit> and mixed carbonates with menthol (s) and polyols according to <patcit id="pcit0067" dnum="DE4226043"><text>DE 4 226 043</text></patcit> and menthone ketals according to <patcit id="pcit0068" dnum="EP0507190A"><text>EP 0 507 190</text></patcit> described.

0254Menthyl monoesters of diacids <patcit id="pcit0069" dnum="US5725865A"><text>US 5,725,865</text></patcit> and <patcit id="pcit0070" dnum="US5843466A"><text>US 5,843,466</text></patcit> are interesting naturally occurring alternatives, but cannot reach the strength of the previously described cooling agents in sensory tests.

0255In <nplcit id="ncit0045" npl-type="s"><text>J. Soc. Cosmet. Chem. 1978, 29, 185-200</text></nplcit> the results of a study on approximately 1200 compounds were presented, in which the compounds L-menthane carboxylic acid<i>N</i>-ethylamide ("WS3") and in particular <i>N</i>^α- (L-Menthancarbonyl) glycine ethyl ester ("WS5") as the strongest cooling agents were found. The latter, however, has the disadvantage of being sensitive to hydrolysis and the corresponding free acid in the case of a strong action<i>N</i>^α- (L-Menthancarbonyl) -glycine to form, which itself shows only a very weak cooling effect. Despite the detailed investigations described, a systematic prediction of the properties of potential cooling agents, in particular their bitterness and / or their other trigeminal effects, is neither possible nor described. Many of the molecules in the class of menthane carboxamides, for example, are strongly cooling, but often show pronounced bitter notes (e.g. menthane carboxylic acid N- (alkyloxyalkyl) amides <patcit id="pcit0071" dnum="JP2004059474B"><text>JP 2004059474</text></patcit>) or are additionally strongly irritating (WS5: N - [[5-methyl-2- (1-methylethyl) cyclohexyl] carbonyl] glycine ethyl ester, <patcit id="pcit0072" dnum="US20050222256A"><text>US 2005/0222256</text></patcit>).

0256<i>N</i>^α- (Menthancarbonyl) alkyloxyalkylamides have been described in <patcit id="pcit0073" dnum="JP2004059474B"><text>JP 2004059474</text></patcit> described. However, with a strong cooling effect and high hydrolysis stability, these have the disadvantage of being extremely bitter, and are therefore not usable in foodstuffs and also in cosmetic products used for facial care.

0257Furthermore, menthyl glyoxylates and their hydrates are in <patcit id="pcit0074" dnum="JP2005343795B"><text>JP 2005343795</text></patcit> have been described as cooling substances.

0258Overviews of the cooling agents manufactured and used so far can be found at <nplcit id="ncit0046" npl-type="s"><text>M. Erman, Perfumer &amp; Flavorist 32 (10), 20-35 (2007</text></nplcit><b>)</b> and <nplcit id="ncit0047" npl-type="b"><text>ML Dewis in DJ Rowe, Chemistry and Technology of Flavors and Fragrances, Blackwell Publishing Ltd, Oxford 2005, p. 212-222</text></nplcit>.

0259It was the primary object of the present special aspect of the invention to specify new agents which have a particular physiological cooling action and are used in food and / or luxury foods and / or oral care products and / or (oral) pharmaceutical preparations and / or cosmetic preparations as cooling substances ( Cooling agents) can be used. The connections or Mixtures of compounds should preferably have a taste which is as weak as possible, in particular taste little or not at all bitter and should not be irritating if possible.

0260This object is achieved according to the invention by the use of an agent comprising at least one, two, three or more of the compounds selected from group A (Table 0) consisting of<tables id="tabl0004" num="0004"><table frame="all"><title><b>Table 0</b></title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="56mm" /><colspec colnum="3" colname="col3" colwidth="101mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry><entry valign="middle">Designation in Tables A, B or C according to Test Example 1 (see below)</entry></row></thead><tbody><row><entry valign="middle">1</entry><entry valign="middle"><chemistry id="chem0019" num="0019"><img file="EP3663366A2_D0019.tif" /></chemistry></entry><entry valign="middle">1-1</entry></row><row><entry valign="middle">2</entry><entry valign="middle"><chemistry id="chem0020" num="0020"><img file="EP3663366A2_D0020.tif" /></chemistry></entry><entry valign="middle">1-2</entry></row><row><entry valign="middle">3</entry><entry valign="middle"><chemistry id="chem0021" num="0021"><img file="EP3663366A2_D0021.tif" /></chemistry></entry><entry valign="middle">1-5</entry></row><row><entry valign="middle">4</entry><entry valign="middle"><chemistry id="chem0022" num="0022"><img file="EP3663366A2_D0022.tif" /></chemistry></entry><entry valign="middle">1-4</entry></row><row><entry valign="middle">5</entry><entry valign="middle"><chemistry id="chem0023" num="0023"><img file="EP3663366A2_D0023.tif" /></chemistry></entry><entry valign="middle">1-3</entry></row><row><entry valign="middle">6</entry><entry valign="middle"><chemistry id="chem0024" num="0024"><img file="EP3663366A2_D0024.tif" /></chemistry></entry><entry valign="middle">1-6/1-7</entry></row><row><entry valign="middle">7</entry><entry valign="middle"><chemistry id="chem0025" num="0025"><img file="EP3663366A2_D0025.tif" /></chemistry></entry><entry valign="middle">Not mentioned</entry></row><row><entry valign="middle">8</entry><entry valign="middle"><chemistry id="chem0026" num="0026"><img file="EP3663366A2_D0026.tif" /></chemistry></entry><entry valign="middle">Not mentioned</entry></row><row><entry valign="middle">9</entry><entry valign="middle"><chemistry id="chem0027" num="0027"><img file="EP3663366A2_D0027.tif" /></chemistry></entry><entry valign="middle">2-1</entry></row><row><entry valign="middle">10</entry><entry valign="middle"><chemistry id="chem0028" num="0028"><img file="EP3663366A2_D0028.tif" /></chemistry></entry><entry valign="middle">2-15</entry></row><row><entry valign="middle">11</entry><entry valign="middle"><chemistry id="chem0029" num="0029"><img file="EP3663366A2_D0029.tif" /></chemistry></entry><entry valign="middle">2-16</entry></row><row><entry valign="middle">12</entry><entry valign="middle"><chemistry id="chem0030" num="0030"><img file="EP3663366A2_D0030.tif" /></chemistry></entry><entry valign="middle">2-17</entry></row><row><entry valign="middle">13</entry><entry valign="middle"><chemistry id="chem0031" num="0031"><img file="EP3663366A2_D0031.tif" /></chemistry></entry><entry valign="middle">2-18</entry></row><row><entry valign="middle">14</entry><entry valign="middle"><chemistry id="chem0032" num="0032"><img file="EP3663366A2_D0032.tif" /></chemistry></entry><entry valign="middle">2-19</entry></row><row><entry valign="middle">15</entry><entry valign="middle"><chemistry id="chem0033" num="0033"><img file="EP3663366A2_D0033.tif" /></chemistry></entry><entry valign="middle">2-5</entry></row><row><entry valign="middle">16</entry><entry valign="middle"><chemistry id="chem0034" num="0034"><img file="EP3663366A2_D0034.tif" /></chemistry></entry><entry valign="middle">2-2</entry></row><row><entry valign="middle">17</entry><entry valign="middle"><chemistry id="chem0035" num="0035"><img file="EP3663366A2_D0035.tif" /></chemistry></entry><entry valign="middle">2-14</entry></row><row><entry valign="middle">18</entry><entry valign="middle"><chemistry id="chem0036" num="0036"><img file="EP3663366A2_D0036.tif" /></chemistry></entry><entry valign="middle">2-7/2-8</entry></row><row><entry valign="middle">19</entry><entry valign="middle"><chemistry id="chem0037" num="0037"><img file="EP3663366A2_D0037.tif" /></chemistry></entry><entry valign="middle">2-3</entry></row><row><entry valign="middle">20</entry><entry valign="middle"><chemistry id="chem0038" num="0038"><img file="EP3663366A2_D0038.tif" /></chemistry></entry><entry valign="middle">Not mentioned</entry></row><row><entry valign="middle">21</entry><entry valign="middle"><chemistry id="chem0039" num="0039"><img file="EP3663366A2_D0039.tif" /></chemistry></entry><entry valign="middle">Not mentioned</entry></row><row><entry valign="middle">22</entry><entry valign="middle"><chemistry id="chem0040" num="0040"><img file="EP3663366A2_D0040.tif" /></chemistry></entry><entry valign="middle">Not mentioned</entry></row><row><entry valign="middle">23</entry><entry valign="middle"><chemistry id="chem0041" num="0041"><img file="EP3663366A2_D0041.tif" /></chemistry></entry><entry valign="middle">3-1</entry></row><row><entry valign="middle">24</entry><entry valign="middle"><chemistry id="chem0042" num="0042"><img file="EP3663366A2_D0042.tif" /></chemistry></entry><entry valign="middle">3-6</entry></row><row><entry valign="middle" /><entry valign="middle"><chemistry id="chem0043" num="0043"><img file="EP3663366A2_D0043.tif" /></chemistry></entry><entry valign="middle" /></row><row><entry valign="middle">25</entry><entry valign="middle">R = H</entry><entry valign="middle">3-25</entry></row><row><entry valign="middle">26</entry><entry valign="middle">R = Me</entry><entry valign="middle">3-32</entry></row><row><entry valign="middle">27</entry><entry valign="middle">R = MeO</entry><entry valign="middle">3-17</entry></row><row><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /></row><row><entry valign="middle" /><entry valign="middle"><chemistry id="chem0044" num="0044"><img file="EP3663366A2_D0044.tif" /></chemistry></entry><entry valign="middle" /></row><row><entry valign="middle">28</entry><entry valign="middle">R = H</entry><entry valign="middle">3-27</entry></row><row><entry valign="middle">29</entry><entry valign="middle">R = Me</entry><entry valign="middle">3-34</entry></row><row><entry valign="middle">30</entry><entry valign="middle">R = MeO</entry><entry valign="middle">3-20</entry></row></tbody></tgroup></table></tables>

0261in a concentration of 0.1 ppm to 10% by weight based on the total weight of the agent for achieving a cooling effect on the skin or mucous membrane, which is compared with the cooling effect of an agent of the same composition, in which only the compound or compounds selected from the group A are replaced by menthane carboxylic acid N-ethylamide in the same concentration, extended by at least 10 minutes, for non-therapeutic purposes or for the manufacture of a medicinal product.

0262The names of the connections are as follows:<ul id="ul0019" list-style="none"><li><u>LN 1</u>2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan-] -1-one</li><li><u>LN 2</u>2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</li><li><u>LN 3</u>2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3] dithian] -1-one</li><li><u>LN 4</u>2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithian] -1-one</li><li><u>LN 5</u>5,6,10b, 11-tetrahydro-3-methyl-spiro [12H-benzo [a] furo [3,4-f] quinolizine-12,2 '</li><li><u>LN 6</u>5,6,10b, 11-tetrahydro-3-methyl-spiro [12H-benzo [a] furo [3,4-f] quinolizine-12,2 '- [1,3] dithian] -1 (3H) on</li><li><u>LN 7</u>2,3,4,5,6,10b, 11,12-octahydro-3-methyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</li><li><u>LN 8</u>2,3,4,5,6,10b, 11,12-octahydro-3-methyl-spiro [4b-azachrysen-12,2 '- [1,3] dithian] -1-one</li><li><u>LN 9</u>Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</li><li><u>LN 10</u>Isopropyl (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) ammonium citrate</li><li><u>LN 11</u>Isopropyl (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) ammonium fumarate</li><li><u>LN 12</u>Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) ammonium malate</li><li><u>LN 13</u>Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) ammonium tartrate</li><li><u>LN 14</u>Isopropyl (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) ammonium succinate</li><li><u>LN 15</u>sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</li><li><u>LN 16</u>Cyclopentyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</li><li><u>LN 17</u>(5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) isopropylamine</li><li><u>LN 18</u>(1,2-dimethyl-propyl) - (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</li><li><u>LN 19</u>Cyclobutyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amines</li><li><u>LN 20</u>Cyclobutyl- (5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) amines</li><li><u>LN 21</u>Cyclopentyl- (5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) amines</li><li><u>LN 22</u>sec-butyl- (5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) amines</li><li><u>LN 23</u>3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</li><li><u>LN 24</u>3,4-methylenedioxycinnamic acid-N, N-diphenylamide</li><li><u>LN 25</u>Cinnamic acid-N-cyclohexyl-N-2-pyridylamide</li><li><u>LN 26</u>4-methylcinnamic acid N-cyclohexyl-N-2-pyridylamide</li><li><u>LN 27</u>4-methoxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</li><li><u>LN 28</u>Cinnamic acid-N, N-diphenylamide</li><li><u>LN 29</u>4-methylcinnamic acid-N, N-diphenylamide</li><li><u>LN 30</u>4-methoxycinnamic acid-N, N-diphenylamide</li></ul>

0263If there are differences between the name and the respective formula picture, the statement of the formula picture is decisive.

0264In order to achieve the object according to the invention, agents with active ingredients which could impart a particularly long-lasting sensation of cooling were sought. In addition, these agents should preferably be able to convey particularly intense and / or rapidly occurring cooling impressions.

0265The above-mentioned conventional cooling substances known in the prior art all show a more or less identical cooling behavior on the oral mucosa. The cooling sensation conveyed by them sets in after about 0.5 minutes. but then flattens out again relatively quickly after a peak at 3 to 5 minutes, the cooling overall being clearly perceptible for a maximum of 30 minutes and experience has shown that the intensity and duration can be influenced only slightly by changing the dosage. On the part of consumers, however, there is a desire for a particularly long-lasting cooling effect, which is associated with a corresponding feeling of freshness and well-being for the user.

0266It has surprisingly been found that, in particular in the compounds listed in Table 0, have the common property <i>in vivo</i> to achieve a particularly long cooling effect on the skin or mucous membrane. This was not predictable for the TRPM8 agonists mentioned in this application, nor does it apply to all of these agonists.

0267So far there has been no knowledge in the prior art that the compounds from Table 0 are capable of imparting a cooling effect at all. In order to quantify the long-lasting cooling effect, comparative tests with menthan-3-carboxylic acid-N-ethylamide are carried out. For these comparative experiments, the person skilled in the art exchanges the compound to be used according to the invention or the compounds with menthan-3-carboxylic acid-N-ethylamide (also WS3) in the same concentration. Then the cooling effects of the respective agents are compared with each other, as demonstrated by the test example for toothpaste. If the compounds to be used according to the invention (the compounds from Table 0) are present in the agent to be investigated in a concentration of more than 100 ppm, it is preferred that the agent to be tested is so evaluated for evaluating whether the cooling effect is extended compared to WS3 to dilute that the compounds to be used according to the invention (from Table 0) are present in a concentration of 100 ppm. Of course, the same dilution step must also be carried out for the comparison agent that contains WS3.

0268In this context, it is preferred that in the corresponding comparisons the cooling effect of the agents with the compounds to be used according to the invention (from Table 0) is extended by at least 15 minutes, more preferably at least 20 minutes and particularly preferably at least 30 minutes compared to the comparative experiments

0269In addition, it is preferred that after ten minutes the perceived cooling intensity on a scale of 0-9 µm ≥ 1, preferably ≥ 2, more preferably ≥ 3 and particularly preferably ≥ 4 compared to an agent of the same composition, in which only the compound to be used according to the invention Menthan-3-carboxylic acid-N-ethylamide was replaced in the same concentration, is increased.

0270As an alternative or in addition, it is preferred that the perceived intensity on the same scale after 20 minutes is correspondingly increased by ≥ 1, preferably ≥ 2, particularly preferably ≥ 3 and very particularly preferably greater than or equal to 4.

0271As an alternative or in addition, it is preferred that the perceived intensity is increased by ≥ 1, more preferably by ≥ 2 after 30 minutes under the conditions described above and / or the perceived intensity or increased by ≥ 1, preferably ≥ 2 after 45 minutes after the minutes is.

0272It should be pointed out once again that the comparative tests with regard to the extension of the cooling effect to the comparative substance WS3 should, in case of doubt, be carried out analogously to test example 2, it being preferred that at concentrations in the compounds to be used according to the invention (compounds of Table 0) of> 100 ppm a dilution step takes place on the entire medium, so that these compounds are only contained in a concentration of 100 ppm in the agent to be tested and the dilution step is carried out analogously in the comparative agent (the agent containing WS3).

0273It is also preferred that the test panel (compare test example (2) comprises at least 6 people) and that the intensity impression values ​​are mathematically averaged.

0274The compounds to be used according to the invention for the special aspect of the invention (the compound in Table 0) can optionally be used as isomer mixtures, racemates or pure enantiomers.

0275The compounds to be used according to the invention are accessible synthetically in a manner known per se. A number of manufacturing examples can be found later in this text. Surprisingly, the compounds to be used according to the invention (the compounds in Table 0) show hardly any other trigeminal effects such as sharpness, tingling or anesthetic and are not bitter. At the same time, the compounds according to the invention are hydrolysis-stable within the scope of the customary formulations and preparation conditions in the range from pH 1 to pH 12, in particular in the range from pH 4 to pH 9, based on water-containing preparations, so that the compounds and mixtures according to the invention in preparations are stable for a long time , so that the respective preparation itself has a long shelf life.

0276The invention also relates to an agent selected from the group consisting of aroma mixture and nutrition, oral hygiene or pleasure-serving pharmaceutical or cosmetic preparation comprising one, two, three or more of the compounds selected from group B consisting of<tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="56mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">1</entry><entry valign="middle"><chemistry id="chem0045" num="0045"><img file="EP3663366A2_D0045.tif" /></chemistry></entry></row><row><entry valign="middle">3</entry><entry valign="middle"><chemistry id="chem0046" num="0046"><img file="EP3663366A2_D0046.tif" /></chemistry></entry></row><row><entry valign="middle">4</entry><entry valign="middle"><chemistry id="chem0047" num="0047"><img file="EP3663366A2_D0047.tif" /></chemistry></entry></row><row><entry valign="middle">6</entry><entry valign="middle"><chemistry id="chem0048" num="0048"><img file="EP3663366A2_D0048.tif" /></chemistry></entry></row><row><entry valign="middle">7</entry><entry valign="middle"><chemistry id="chem0049" num="0049"><img file="EP3663366A2_D0049.tif" /></chemistry></entry></row><row><entry valign="middle">8</entry><entry valign="middle"><chemistry id="chem0050" num="0050"><img file="EP3663366A2_D0050.tif" /></chemistry></entry></row><row><entry valign="middle">10</entry><entry valign="middle"><chemistry id="chem0051" num="0051"><img file="EP3663366A2_D0051.tif" /></chemistry></entry></row><row><entry valign="middle">11</entry><entry valign="middle"><chemistry id="chem0052" num="0052"><img file="EP3663366A2_D0052.tif" /></chemistry></entry></row><row><entry valign="middle">12</entry><entry valign="middle"><chemistry id="chem0053" num="0053"><img file="EP3663366A2_D0053.tif" /></chemistry></entry></row><row><entry valign="middle">13</entry><entry valign="middle"><chemistry id="chem0054" num="0054"><img file="EP3663366A2_D0054.tif" /></chemistry></entry></row><row><entry valign="middle">14</entry><entry valign="middle"><chemistry id="chem0055" num="0055"><img file="EP3663366A2_D0055.tif" /></chemistry></entry></row><row><entry valign="middle">15</entry><entry valign="middle"><chemistry id="chem0056" num="0056"><img file="EP3663366A2_D0056.tif" /></chemistry></entry></row><row><entry valign="middle">16</entry><entry valign="middle"><chemistry id="chem0057" num="0057"><img file="EP3663366A2_D0057.tif" /></chemistry></entry></row><row><entry valign="middle">17</entry><entry valign="middle"><chemistry id="chem0058" num="0058"><img file="EP3663366A2_D0058.tif" /></chemistry></entry></row><row><entry valign="middle">18</entry><entry valign="middle"><chemistry id="chem0059" num="0059"><img file="EP3663366A2_D0059.tif" /></chemistry></entry></row><row><entry valign="middle">19</entry><entry valign="middle"><chemistry id="chem0060" num="0060"><img file="EP3663366A2_D0060.tif" /></chemistry></entry></row><row><entry valign="middle">20</entry><entry valign="middle"><chemistry id="chem0061" num="0061"><img file="EP3663366A2_D0061.tif" /></chemistry></entry></row><row><entry valign="middle">21</entry><entry valign="middle"><chemistry id="chem0062" num="0062"><img file="EP3663366A2_D0062.tif" /></chemistry></entry></row><row><entry valign="middle">22</entry><entry valign="middle"><chemistry id="chem0063" num="0063"><img file="EP3663366A2_D0063.tif" /></chemistry></entry></row><row><entry valign="middle">24</entry><entry valign="middle"><chemistry id="chem0064" num="0064"><img file="EP3663366A2_D0064.tif" /></chemistry></entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">25</entry><entry valign="middle"><chemistry id="chem0065" num="0065"><img file="EP3663366A2_D0065.tif" /></chemistry></entry></row><row><entry valign="middle">with R = H</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">26</entry><entry valign="middle"><chemistry id="chem0066" num="0066"><img file="EP3663366A2_D0066.tif" /></chemistry></entry></row><row><entry valign="middle">with R = Me</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">27</entry><entry valign="middle"><chemistry id="chem0067" num="0067"><img file="EP3663366A2_D0067.tif" /></chemistry></entry></row><row><entry valign="middle">with R = MeO</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">28</entry><entry valign="middle"><chemistry id="chem0068" num="0068"><img file="EP3663366A2_D0068.tif" /></chemistry></entry></row><row><entry valign="middle">with R = H</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">29</entry><entry valign="middle"><chemistry id="chem0069" num="0069"><img file="EP3663366A2_D0069.tif" /></chemistry></entry></row><row><entry valign="middle">with R = Me</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">30</entry><entry valign="middle"><chemistry id="chem0070" num="0070"><img file="EP3663366A2_D0070.tif" /></chemistry></entry></row><row><entry valign="middle">with R = MeO</entry></row></tbody></tgroup></table></tables>

0277Furthermore, the invention preferably relates to an i) above-described agent according to the invention and / or an ii) agent selected from the group consisting of aroma mixture and nutrition, oral hygiene or pleasure-serving pharmaceutical or cosmetic preparation comprising a two, three or more of the compounds selected from group C consisting of<tables id="tabl0006" num="0006"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="50mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">2</entry><entry valign="middle"><chemistry id="chem0071" num="0071"><img file="EP3663366A2_D0071.tif" /></chemistry></entry></row><row><entry valign="middle">5</entry><entry valign="middle"><chemistry id="chem0072" num="0072"><img file="EP3663366A2_D0072.tif" /></chemistry></entry></row><row><entry valign="middle">9</entry><entry valign="middle"><chemistry id="chem0073" num="0073"><img file="EP3663366A2_D0073.tif" /></chemistry></entry></row><row><entry valign="middle">23</entry><entry valign="middle"><chemistry id="chem0074" num="0074"><img file="EP3663366A2_D0074.tif" /></chemistry></entry></row></tbody></tgroup></table></tables>wherein the compound or the compounds of group C is contained in a concentration of 0.05 ppm - &lt;0.1 ppm or 0.1 ppm to 50% by weight based on the total weight of the preparation, preferably with the proviso that in the case (ii) the preparation does not contain a mouthwash with the composition of one liter each<tables id="tabl0007" num="0007"><table frame="none"><tgroup cols="2" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="96mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><tbody><row><entry valign="bottom">Ethanol 95%</entry><entry valign="bottom">177mL</entry></row><row><entry valign="bottom">Sorbitol 70%</entry><entry valign="bottom">250 G</entry></row><row><entry valign="bottom">Compound of formula 2, 5, 9 or 23 as a 1% solution in ethanol</entry><entry valign="bottom">50mL</entry></row><row><entry valign="bottom">Peppermint oil,</entry><entry valign="bottom">0.30 g</entry></row><row><entry valign="bottom">Methyl salicylate</entry><entry valign="bottom">0.64 g</entry></row><row><entry valign="bottom">Eucalyptol</entry><entry valign="bottom">0.922 g</entry></row><row><entry valign="bottom">Thymol</entry><entry valign="bottom">0.639 g</entry></row><row><entry valign="bottom">Benzoic acid</entry><entry valign="bottom">1.50 g</entry></row><row><entry valign="bottom">Pluronic® F127 non-ionic surfactant</entry><entry valign="bottom">5.00 g</entry></row><row><entry valign="bottom">Sodium saccharin</entry><entry valign="bottom">0.60 g</entry></row><row><entry valign="bottom">Sodium citrate</entry><entry valign="bottom">0.30 g</entry></row><row><entry valign="bottom">citric acid</entry><entry valign="bottom">0.10 g</entry></row><row><entry valign="bottom">Water qs</entry><entry valign="bottom">1 liter</entry></row></tbody></tgroup></table></tables>is.

0278It should be noted that the distinction between the compounds of group B and the compounds of group C is only due to formal patent law reasons, but not technical aspects.

0279Preferred in the agents described for the special aspect of the invention are the compounds to be used according to the invention (compounds in Table 0) in a (total) concentration of 0.05 ppm to 50% by weight, based on the total weight of the preparation or agent contain. This area is composed in particular of the following sub-areas: 0.05 ppm - &lt;0.1 ppm. 0.1 ppm - 1,000 ppm and 0.1 - 50% by weight. Preferred concentration ranges, based on the total weight of the preparation or of the agent, are the following, the concentration ranges in the order listed being further preferred over the preceding enumeration element: 0.05 ppm - 10 wt%. 0.5 ppm-5 wt%, 1 ppm, 2.5 wt%.

0280An advantage of the agents according to the invention, in particular those in the preferred variant, is that they are able to impart a long-lasting cooling effect on the skin or mucous membrane, without the compounds to be used according to the invention (the compounds in Table 0) being used for the particular purpose Prevent or restrict by means.

0281In this context, it should be pointed out that the means according to the invention according to the special part of the invention apply analogously to the description of the description of the general part of the invention (in particular chapters 3-5). Particularly preferred variants for the agents according to the invention in accordance with the special part of the invention are additionally described in this chapter.

0282An agent according to the invention, in particular one according to the special aspect of the invention, is preferred<ul id="ul0020" list-style="none"><li>(1) one or more further substances with a physiological cooling effect, the further substance or one, several or all of the further substances (i) causing a taste effect or (ii) causing no taste effect, and or</li><li>(2) one or more flavoring substances without a physiological cooling effect and / or</li><li>(3) one or more trigeminal or mouthwashing substances without a physiological cooling effect and or</li><li>(4) (iii) one or (iv) multiple compounds, which in case (iv) are independent of each other or together</li></ul>additionally cause a taste-modulating effect and / or a trigeminal and / or mouth-irritating stimulus.

0283Such an agent further preferably comprises one or more further substances with a physiological cooling effect without a taste effect. This avoids that, for example, only aromas with a minty aroma character can be obtained with the agent according to the invention.

0284An agent according to the invention is very particularly preferred comprising, as component (2), one or more aroma substances without a physiological cooling effect and / or as component (3) one or more compounds which, independently of one another or together, additionally have a taste-modulating effect and / or a trigiminal and / or cause a mouth-irritating stimulus, the trigiminal stimulus preferably not being a physiological cooling effect. In particular, agents according to the invention which contain the latter components (2) and (3) at the same time have a pleasant cooling effect and a balanced sensory profile with a high impact, that is to say a high initial taste impression.

0285The special aspect of the invention preferably also relates to agents, in particular as nutritional, oral hygiene or pleasure-serving or pharmaceutical or cosmetic preparations, which contain an amount of a compound to be used according to the invention (compound from the compound) to achieve a physiological cooling effect on the skin and / or mucous membrane Table 0) or a mixture of such compounds to be used according to the invention. In particular, the amount of this compound or mixture used should be sufficient to achieve a physiological cooling effect on the mucous membrane in the mouth, nose and / or throat area.

0286In this context, it should be noted that the terms "means" and "preparation" can be used synonymously. However, it is preferred that a preparation has to be produced by means of a work step that goes beyond simply mixing the individual compounds. Such a step can serve, for example, to produce a suspension or an emulsification.

0287Preferred agents according to the invention comprise customary basic substances, auxiliaries and additives for nutrition, oral hygiene or pleasure or pharmaceutical or cosmetic preparations. Preferred preparations according to the invention contain 0.000005% by weight to 20% by weight, preferably 0.00001 to 10% by weight, particularly preferably 0.0001% by weight to 0.5% by weight, of compounds to be used according to the invention Table 0, based on the total weight of the preparation. Other components, in particular components (1) (other substances with a physiological cooling effect), (2) (flavorings without a physiological cooling effect) and / or (3) (trigeminal or mouthwashing substances without a physiological cooling effect) (as described above) and other common reasons -, Auxiliaries and additives can be present in amounts of 0.0000001 to 99.99% by weight, preferably 10 to 80% by weight, based on the total weight of the preparation. Furthermore, the preparations according to the invention can contain water in an amount of up to 99.99% by weight, preferably 5 to 80% by weight, based on the total weight of the preparation.

0288An agent according to the invention is further preferred, at least one of the compounds selected from group A being selected from group D consisting of<tables id="tabl0008" num="0008"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="56mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">1</entry><entry valign="middle"><chemistry id="chem0075" num="0075"><img file="EP3663366A2_D0075.tif" /></chemistry></entry></row><row><entry valign="middle">2</entry><entry valign="middle"><chemistry id="chem0076" num="0076"><img file="EP3663366A2_D0076.tif" /></chemistry></entry></row><row><entry valign="middle">3</entry><entry valign="middle"><chemistry id="chem0077" num="0077"><img file="EP3663366A2_D0077.tif" /></chemistry></entry></row><row><entry valign="middle">4</entry><entry valign="middle"><chemistry id="chem0078" num="0078"><img file="EP3663366A2_D0078.tif" /></chemistry></entry></row><row><entry valign="middle">9</entry><entry valign="middle"><chemistry id="chem0079" num="0079"><img file="EP3663366A2_D0079.tif" /></chemistry></entry></row><row><entry valign="middle">11</entry><entry valign="middle"><chemistry id="chem0080" num="0080"><img file="EP3663366A2_D0080.tif" /></chemistry></entry></row><row><entry valign="middle">12</entry><entry valign="middle"><chemistry id="chem0081" num="0081"><img file="EP3663366A2_D0081.tif" /></chemistry></entry></row><row><entry valign="middle">13</entry><entry valign="middle"><chemistry id="chem0082" num="0082"><img file="EP3663366A2_D0082.tif" /></chemistry></entry></row><row><entry valign="middle">14</entry><entry valign="middle"><chemistry id="chem0083" num="0083"><img file="EP3663366A2_D0083.tif" /></chemistry></entry></row><row><entry valign="middle">15</entry><entry valign="middle"><chemistry id="chem0084" num="0084"><img file="EP3663366A2_D0084.tif" /></chemistry></entry></row><row><entry valign="middle">16</entry><entry valign="middle"><chemistry id="chem0085" num="0085"><img file="EP3663366A2_D0085.tif" /></chemistry></entry></row><row><entry valign="middle">17</entry><entry valign="middle"><chemistry id="chem0086" num="0086"><img file="EP3663366A2_D0086.tif" /></chemistry></entry></row><row><entry valign="middle">23</entry><entry valign="middle"><chemistry id="chem0087" num="0087"><img file="EP3663366A2_D0087.tif" /></chemistry></entry></row><row><entry valign="middle">24</entry><entry valign="middle"><chemistry id="chem0088" num="0088"><img file="EP3663366A2_D0088.tif" /></chemistry></entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">25</entry><entry valign="middle"><chemistry id="chem0089" num="0089"><img file="EP3663366A2_D0089.tif" /></chemistry></entry></row><row><entry valign="middle">with R = H</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">26</entry><entry valign="middle"><chemistry id="chem0090" num="0090"><img file="EP3663366A2_D0090.tif" /></chemistry></entry></row><row><entry valign="middle">with R = Me</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">27</entry><entry valign="middle"><chemistry id="chem0091" num="0091"><img file="EP3663366A2_D0091.tif" /></chemistry></entry></row><row><entry valign="middle">with R = MeO</entry></row></tbody></tgroup></table></tables>

0289An agent according to the invention is particularly preferred, at least one of the compounds selected from group A being selected from group E consisting of<tables id="tabl0009" num="0009"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="52mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">1</entry><entry valign="middle"><chemistry id="chem0092" num="0092"><img file="EP3663366A2_D0092.tif" /></chemistry></entry></row><row><entry valign="middle">2</entry><entry valign="middle"><chemistry id="chem0093" num="0093"><img file="EP3663366A2_D0093.tif" /></chemistry></entry></row><row><entry valign="middle">9</entry><entry valign="middle"><chemistry id="chem0094" num="0094"><img file="EP3663366A2_D0094.tif" /></chemistry></entry></row><row><entry valign="middle">11</entry><entry valign="middle"><chemistry id="chem0095" num="0095"><img file="EP3663366A2_D0095.tif" /></chemistry></entry></row><row><entry valign="middle">14</entry><entry valign="middle"><chemistry id="chem0096" num="0096"><img file="EP3663366A2_D0096.tif" /></chemistry></entry></row><row><entry valign="middle">15</entry><entry valign="middle"><chemistry id="chem0097" num="0097"><img file="EP3663366A2_D0097.tif" /></chemistry></entry></row><row><entry valign="middle">16</entry><entry valign="middle"><chemistry id="chem0098" num="0098"><img file="EP3663366A2_D0098.tif" /></chemistry></entry></row><row><entry valign="middle">17</entry><entry valign="middle"><chemistry id="chem0099" num="0099"><img file="EP3663366A2_D0099.tif" /></chemistry></entry></row><row><entry valign="middle">23</entry><entry valign="middle"><chemistry id="chem0100" num="0100"><img file="EP3663366A2_D0100.tif" /></chemistry></entry></row><row><entry valign="middle">24</entry><entry valign="middle"><chemistry id="chem0101" num="0101"><img file="EP3663366A2_D0101.tif" /></chemistry></entry></row></tbody></tgroup></table></tables>

0290The compounds of Table 0 and / or their mixtures to be used according to the invention are preferably used to produce a medicament which is used to combat or relieve symptoms of cough, runny nose, mouth, nose, throat or pharyngitis, sore throat or hoarseness symptoms .

0291Another aspect of the special aspect of the present invention relates to a therapeutic or non-therapeutic method for achieving a physiological cooling effect on the skin and / or a mucous membrane, with the following step:<ul id="ul0021" list-style="dash" compact="compact"><li>Application of an amount of an agent according to the invention sufficient to achieve a physiological cooling effect</li></ul>on the skin and / or a mucous membrane.

0292It is preferred in the sense of the special aspect of the invention that the agent according to the invention is an aroma mixture which comprises one or more aroma substances and / or one or more further cooling substances (cooling substances which are not a compound of Table 0) for Flavoring of finished goods made using the flavor mixture.

0293In preparations (aroma mixtures) which are used for flavoring toothpastes and toothpastes, the content of the substances to be used according to the invention in Table 00.001 to 50 wt .-%; a range from 0.005 to 5% by weight is preferred, and a range from 0.01 to 2% by weight is particularly preferred. With conventional dosages of the flavors between 0.5 and 1.5% by weight, based on the ready-to-use toothpastes and creams, the content of the substances of the formula I to be used according to the invention is then 0.000005 to 0.75% by weight based on the finished product; a range of 0.000025 to 0.075% by weight is preferred, and a content of 0.00005 to 0.03% by weight is particularly preferred.

0294In preparations (flavor mixtures) which are used for flavoring chewing gum, the content of the substances to be used according to the invention in Table 0 is 0.005 to 10% by weight; a range from 0.01 to 5% by weight is preferred, and a range from 0.05 to 2.5% by weight is particularly preferred. With a customary dosage of the flavors of 1-2% by weight, based on the ready-to-use chewing gum, the content of the substances in Table 0 to be used according to the invention is then 0.00005 to 0.2% by weight based on the finished product; a range of 0.0001 to 0.1% by weight is preferred, and a content of 0.0005 to 0.05% by weight is particularly preferred.

0295In preparations (aroma mixtures) which are used to flavor mouthwashes and mouthwashes, the content of the substances to be used according to the invention in Table 0 is 0.01 to 10% by weight; a range from 0.05 to 5% by weight is preferred, and a range from 0.1 to 2.5% by weight is particularly preferred. With a customary dosage of the aroma of 2-4% by weight, based on a ready-to-use mouthwash concentrate, the content of the substances to be used according to the invention in Table 0 is then 0.0002 to 0.4% by weight, based on the finished product; a range of 0.001 to 0.2% by weight is preferred, and a content of 0.002 to 0.1% by weight is particularly preferred. In ready-to-use mouthwashes and rinses, the content of the substances to be used according to the invention in Table 0 is 0.00001 to 0.03% by weight, based on the finished product, with a customary dosage of the aroma mixture of 0.1-0.3% by weight ; a range of 0.00005 to 0.015% by weight is preferred, and a content of 0.0001 to 0.0075% by weight is particularly preferred.

0296[Aromatic substances are both complex natural raw materials such as extracts and essential oils obtained from plants, or fractions and uniform substances obtained therefrom, and uniform synthetic or biotechnologically derived aromatic substances.

0297Examples of natural raw materials are: Peppermint oils, spearmint oils, mentha arvensis oils, anise oils, clove oils, citrus oils, cinnamon bark oils, wintergreen oils, cassia oils, davana oils, spruce needle oils, eucalyptus oils, fennel oils, star oil oils, geranium oils, geranium oils, camel oils, ginger oils, camomile oils Juniper berry oils, rosemary oils, angelica root oils, and the fractions of these oils.

0298Examples of uniform flavors are: Anethole, menthol, menthone, isomenthone, menthyl acetate, menthofuran, menthyl methyl ether, mint lactone, eucalyptol, limonene, eugenol, pinene, sabine hydrate, 3-octanol, carvone, gamma-octalactone, gamma-nonalactone, germacren-D, viridiflorol, 1,3 5Z-undecatriene, isopulegol, piperiton, 2-butanone, ethyl formate, 3-octyl acetate, isoamyl isovalerate, hexanol, hexanal, cis-3-hexenol, linalool, alpha-terpineol, cis and trans carvy acetate, p-cymol, thymol, 4.8 -Dimethyl-3,7-nonadien-2-one, Damascenon, Damascone, Rose oxide, dimethyl sulfide, fenchol, acetaldehyde diethylacetal, cis-4-heptenal, isobutyraldehyde, isovaleraldehyde, cis-jasmon, anisaldehyde, methyl salicylate, myrtenyl acetate, 8-ocimenylacetate, 2-phenylethyl alcohol, 2-phenylethyl-isobutyranidolate, nerodolate, nerodolate, nerodolate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate, nerate. In the case of chiral compounds, the flavorings mentioned can be present as a racemate, as a single enantiomer or as enantiomerically enriched mixtures.

0299In the nutritional or pleasure-making preparations, the content of the substances to be used according to the invention in Table 0 is 0.000005 to 0.1% by weight; a range from 0.00005 to 0.05% by weight is preferred, and a range from 0.0001 to 0.02% by weight is particularly preferred.

0300In cosmetic preparations, the content of the substances in Table 0 to be used according to the invention is 0.001 to 10% by weight; a range from 0.005 to 5% by weight is preferred, and a range from 0.01 to 2% by weight is particularly preferred.

0301It is particularly preferred according to the invention that the agent according to the invention is a toothpaste according to the special aspect of the invention.

0302A compound selected from the group consisting of consists in particular of the special aspect of the invention<tables id="tabl0010" num="0010"><table frame="all"><title>(Table N)</title><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="12mm" /><colspec colnum="2" colname="col2" colwidth="48mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">7</entry><entry valign="middle"><chemistry id="chem0102" num="0102"><img file="EP3663366A2_D0102.tif" /></chemistry></entry></row><row><entry valign="middle">8</entry><entry valign="middle"><chemistry id="chem0103" num="0103"><img file="EP3663366A2_D0103.tif" /></chemistry></entry></row><row><entry valign="middle">20</entry><entry valign="middle"><chemistry id="chem0104" num="0104"><img file="EP3663366A2_D0104.tif" /></chemistry></entry></row><row><entry valign="middle">21</entry><entry valign="middle"><chemistry id="chem0105" num="0105"><img file="EP3663366A2_D0105.tif" /></chemistry></entry></row><row><entry valign="middle">22</entry><entry valign="middle"><chemistry id="chem0106" num="0106"><img file="EP3663366A2_D0106.tif" /></chemistry></entry></row></tbody></tgroup></table></tables>

0303These compounds listed in Table N were not previously described and in particular also meet the special aspect of the present invention.

0304Further aspects of the present invention result from the following examples and the attached patent claims.

<u>Examples</u>

0305The examples serve only to illustrate the invention, without restricting it. Unless otherwise stated, all information is based on weight.

<u>7. Active ingredient production</u>

0306The active ingredients of structure types 1, 2 and 3 used according to the invention are either compounds known per se or can be prepared by a person skilled in the field of organic synthesis based on known synthesis methods.

0307The following experimental section describes various synthetic methods for a representative cross-section of active substances according to the invention.

0308The invention will now be described with reference to the following, non-limiting exemplary embodiments.

<u>8th. Experimental part, examples</u>

0309The following examples serve to explain the invention. If mengan information is given, it is in% by weight if in doubt.

Reference example 1

-

Cloning of human TRPM8

0310The starting point for the cloning of the human TRPM8 receptor is an LnCaP cDNA library. This is, for example, commercially available (for example from BioChain, Hayward, USA) or can be produced from the androgen-sensitive human prostate adenocarcinoma cell line LnCaP (for example ATCC, CRL1740 or ECACC, 89110211) using standard kits.

0311The coding TRPM8 sequence (cf. <figref idref="f0001 f0002">Fig.1A</figref>; such as<b><u>http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nuccore&amp;id=109689694)</u></b>can be PCR amplified and cloned using standard methods. The human TRPM8 gene isolated in this way was used to produce the plasmid plnd_M8, the construction of which according to the plasmid map<figref idref="f0003">Figure 2</figref> is illustrated.

0312Alternatively, the TRPM8 gene can also be produced synthetically.

Reference example 2

-

Generation of the HEK293 test cells

0313As a test cell system, the human TRPM8 DNA (cf. plasmid plnd-M8 above) was used to produce a stably transfected HEK293 cell line. The HEK293 is preferred which, via the plasmid introduced, offers the possibility of inducing TRPM8 expression by means of tetracycline.

0314Methods for producing suitable test cell systems are known to the person skilled in the art. So you can the manufacture of the cells used according to the invention the information in<nplcit id="ncit0048" npl-type="s"><text>Behrendt HJ et al., Br. J. Pharmacol. 141, 2004, 737-745</text></nplcit> or the dissertation by Behrendt "Comparative functional studies of the heat capsaicin receptor (TRPV1) and the cold menthol receptor (TRPM8) in recombinant and native cell systems", available at http: //www-brs.ub.ruhr-uni -bochum.de/netahtml/HSS/Diss/BehrendtHansJoerg/diss. remove pdf. Reference is expressly made to the disclosure of these publications.

Reference Example 3- Assay on TRPM8 Modulators

0315It will be a test comparable to the test of<nplcit id="ncit0049" npl-type="s"><text> Behrendt HJ et al., Br. J. Pharmacol. 141, 2004, 737-745</text></nplcit>, carried out. The agonization or antagonization of the receptor can be done using a Ca²⁺-sensitive dye (e.g. FURA, Fluo-4 etc.) can be quantified. Agonists alone cause an increase in the Ca²⁺Signal; Antagonists reduce the Ca in the presence of, for example, menthol²⁺Signal (each detected via the dye Fluo-4, which is characterized by Ca²⁺ has other fluorescence properties).

0316First, a fresh culture of transformed HEK cells is produced in a manner known per se in cell culture bottles. The test cells HEK293-TRPM8 are detached from the cell culture bottles using trypsin and 40,000 cells / well are sown with 100 μl medium in 96-well plates (Greiner # 655948 poly-D-lysine-coated). To induce the receptor TRPM8, tetracycline is added to the growth medium (DMEM / HG, 10% FCS tetracycline-free, 4 mM L-glutamine, 15 µg / ml blasticidin, 100 µg / ml hygromycin B, 1 µg / ml tetracycline). The following day, the cells are loaded with Fluo-4AM dye and the test is performed. To do this, proceed as follows:<ul id="ul0022" list-style="dash" compact="compact"><li>Add 100 µl / well staining solution Ca-4 Kit (RB 141, Molecular Devices) to 100 µl medium (DMEM / HG, 10% FCS tetracycline-free, 4 mM L-glutamine, 15 µg / ml blasticidin, 100 µg / ml Hygromycin B, 1 µg / ml tetracycline)</li><li>Incubation in the incubator, 30 minutes / 37 ° C / 5% CO₂, 30 minutes / RT</li><li>Preparation of the test substances (different concentrations in 200 µl HBSS buffer), as well as positive controls (different concentrations of menthol, icilin or ionomycin in 200 µl HBSS buffer) and negative controls (only 200 µl HBSS buffer)</li><li>Add the test substances in amounts of 50 µl / well and measure the change in fluorescence (e.g. in the FLIPR, Molecular Devices or NovoStar, BMG assay device) with 485 nm excitation, 520 nm emission, and evaluate the potency of the various substances / concentrations and determine the EC50 values</li></ul>

0317The test substances are used in triplicates in concentrations of 0.1-200 µM in the assay. Typically, the compounds are kept in DMSO solutions and diluted down to a maximum DMSO concentration of 2% for the assay.

0318The evaluation surprisingly shows that, according to the invention, it was possible for the first time to provide agomists of TRPM8 which are structurally different from previously known agonists, such as (-) menthol, icinin and others from<nplcit id="ncit0050" npl-type="s"><text> Behrendt HJ et al., In Br. J. Pharmacol. 141, 2004, 737-745</text></nplcit> (cf. table 1 there), differentiate significantly and, in addition, sometimes show better activities than (-) menthol, or act comparable to Icilin.

<u>Manufacturing examples</u>

<u>a) Production examples for connections according to structure type 1</u>

0319The preparation of representative compounds of formula I is described in the following section.

0320In principle, the compounds of the formula I can be obtained from the reaction of keto precursors of the formula VI with the keto-reactive compound of the formula YI (see <nplcit id="ncit0051" npl-type="s"><text>Akhrem et al. , Kimiya Geteotsiklicheskikh Soedinenii, 1995, 187-194</text></nplcit>, <nplcit id="ncit0052" npl-type="s"><text>Akhrem et al., Journal of Organic Chemistry of the USSR, 1985, 21 (6), 1227-1232</text></nplcit>) <chemistry id="chem0107" num="0107"><img file="EP3663366A2_D0107.tif" /></chemistry>

0321The various starting materials required for this are also known or can be obtained by known processes.

0322(For making connections of type V-1 see<nplcit id="ncit0053" npl-type="s"><text> Akhrem et al. in Journal of Organic Chemistry of the USSR, 1979, 1247-1252</text></nplcit>, <nplcit id="ncit0054" npl-type="s"><text>Akhrem et al., Izvestia Akademii Nauk SSSR Seria Himiceskaa, 1969, (10), 2338-2339</text></nplcit>, <nplcit id="ncit0055" npl-type="s"><text>Akhrem et al., Doklady Akademii Nauk SSSR, 1972, 203 (1), 95-98</text></nplcit>.)

Preparation Example 1-1: Preparation of Compound 1-1

0323<chemistry id="chem0108" num="0108"><img file="EP3663366A2_D0108.tif" /></chemistry>

0324The production follows the following scheme:<chemistry id="chem0109" num="0109"><img file="EP3663366A2_D0109.tif" /></chemistry>

(1) Preparation of precursor V-1-1

^1-1

0325<chemistry id="chem0110" num="0110"><img file="EP3663366A2_D0110.tif" /></chemistry>

0326A mixture of 40.1 g (0.259 mol) of 2-acetyl-1,3-hexanedione (A), 34.1 g (0.26 mol) of 1,2-dihydroisoquinoline (B) and 254 ml of EtOH are added for 2 hours Heated to reflux. It is slowly cooled and the reaction mixture is concentrated on a rotary evaporator at 50 ° C. The residue is taken up in 230 ml of toluene and 31 ml of n-heptane, the mixture is heated to reflux and slowly cooled to room temperature. The resulting suspension is filtered. The filter residue is washed with 50 ml of toluene and sucked dry. You get the dion<b>V-1-1.</b>

0327Yield: 57 g product (82%), HPLC: 97.4 FI%.

0328¹H-NMR (CDCl₃): m 7.12-7.34; d 4.86; m 4.16-4.26; m 3.35-3.46; m 3.04-3.18; m 2.78-3.01; m 2.55-3.72; m 2.40-2.50; m 2.26-2.40; m 1.90-2.14 [ppm]

(2) Making connection

1-1

032921.4 g of water are placed in a reactor and 75.9 g (0.79 mol) of methanesulfonic acid are added. After the exotherm has subsided, 9.3 g (0.099 mol) of ethanedithiol are added. Then 17.6 g (0.066 mol) of compound are added in portions<b>V-1-1</b> added. The mixture is stirred at room temperature for 17 h. 202 ml of toluene and then 158 g of 25% NaOH are added to the reaction mixture. It is filtered, the aqueous phase is separated off and the organic phase is washed again with 107 g of water. The organic phase is filtered through activated carbon, the filtrate is concentrated and the residue is cooled to 5 ° C. The suspension is filtered and the filter cake is washed with 15 ml of toluene. After drying in a vacuum drying cabinet at 50 ° C. for 2 h, 12.4 g of solid are isolated.

0330The solid is dissolved in 115 ml of toluene and filtered hot over a sand / kieselguhr / activated carbon filter. The filter is rinsed with 15 ml of hot toluene. 80 ml of toluene are distilled off and the concentrated reaction mixture is cooled to -10 ° C. The suspension is filtered and the filter cake is washed with a little cold toluene. It is dried overnight in a vacuum drying cabinet at 50 ° C., whereby compound<b>1-1</b> receives

Yield: 10.5 g (46%), HPLC 99 FI%

Preparation example H1-2: Preparation of compound 1-4

0331<chemistry id="chem0111" num="0111"><img file="EP3663366A2_D0111.tif" /></chemistry>

03324.5 g of the starting compound <b>(V-1-1)</b> are placed in 45 ml of toluene and mixed with 7.3 g of propanedithiol. 9.7 g of trifluoroacetic acid are added and the mixture is stirred at 50 ° C. for 53 h. The reaction mixture is cooled to RT and 12.9 g of 25% sodium hydroxide solution are added. The mixture is stirred at RT for 5 min, the organic phase is separated off and washed twice more with water. The organic phase is concentrated and isopropanol is added several times and concentrated again. It is then purified chromatographically on a silica gel column using heptane / EtOAc as the eluent, giving the desired compound.

Yield: 1.5 g (25%)

Production Example H1-3: Production of 1-2

0333<chemistry id="chem0112" num="0112"><img file="EP3663366A2_D0112.tif" /></chemistry>

(1) Preparation of the precursor

V-1-2

0334<chemistry id="chem0113" num="0113"><img file="EP3663366A2_D0113.tif" /></chemistry>

033519.7 g (0.106 mol) of 2-acetyldimedone and 78 ml of ethanol are introduced and 14.6 g of 1,2-dihydroisoquinoline are added. The mixture is heated to reflux for 2 hours. It is then cooled to room temperature and rotated in at 50 ° C. in a vacuum on a rotary evaporator. 98 ml of toluene are added and the mixture is heated to reflux. It is slowly cooled to 10 ° C., stirred at 10 ° C. for 2 hours and filtered. The filter cake is washed with 25 ml of toluene and then dried in a stream of nitrogen to give the desired compound.

Yield: 30 g (96%), HPLC: 100 FI%

0336¹H-NMR (CDCl₃): m 7.20-7.32; dd 4.98; s 4.83; dtr 4.38; dtr 3.43; m 3.28-3.32; m 3.07-3.19; dtr 2.96; d 2.88; m 2.56-2.76; d 2.29; d 2.17; s 2.14; s 1.08 [ppm]

(2) Making connection

1-2

033726.4 g (89 mmol) compound <b>V-1-2</b> and 161 ml of toluene are introduced and 25.3 g (0.27 mol) of ethanedithiol and 51 g (0.45 mol) of trifluoroacetic acid are added in succession. The mixture is heated to 50 ° C. and stirred for 121 h at the same temperature. 8.4 g (89 mmol) of ethanedithiol and 10.2 g (89 mmol) of trifluoroacetic acid are added and the mixture is stirred at 50 ° C. for a further 21 h. It is cooled to room temperature and 78 ml of 20% sodium hydroxide solution and 50 g of water are added. The aqueous phase is separated off and the organic phase is washed again with 16 g of water. The organic phase is spun in and 50 ml of isopropanol are added to the crude product. The mixture is heated to 60 ° C, inoculated and slowly cooled to 0 ° C. It is filtered and the filter cake is washed with 10 ml of isopropanol. The filter cake is dried in a stream of nitrogen.

0338For purification, 14.6 g of the product are taken up in 145 ml of isopropanol and the mixture is heated to reflux. 132 ml of isopropanol are added to the bottom in portions and then distilled off again. The sump is slowly cooled to 0 ° C and filtered. The filter cake is washed twice with 13 ml of isopropanol and dried overnight at 50 ° C. in vacuo to give the desired compound.

Yield: 13.1 g (42%).

Preparation example H1-4: Preparation of compound 1-5

0339<chemistry id="chem0114" num="0114"><img file="EP3663366A2_D0114.tif" /></chemistry>

03404.5 g of the starting compound <b>V-1-2</b> are placed in 40 ml of toluene and mixed with 6.6 g of propanedithiol. 8.8 g of trifluoroacetic acid are added and the mixture is stirred at 50 ° C. for 50 h. 3.3 g of 1,3-propanedithiol and 3.5 g of trifluoroacetic acid are metered in and the mixture is stirred at 50 ° C. for a further 74 h. The reaction mixture is mixed with 12.7 g of 25% sodium hydroxide solution. The organic phase is separated off and washed twice with water. The organic phase is spun in and isopropanol is then added several times and concentrated again. The crude product is purified on a silica gel column using heptane / EtOAc as the eluent, giving the desired compound.

Yield: 2.9 g (49%)

Preparation example H1-5: Preparation of compound 1-8

0341<chemistry id="chem0115" num="0115"><img file="EP3663366A2_D0115.tif" /></chemistry>

03421 g connection <b>1-2</b> are placed in 4.5 ml of dichloromethane and a solution of 2.65 g of meta-chloroperbenzoic acid in 40 ml of dichloromethane is added within 50 min at 20-23 ° C. The mixture is stirred for 72 h and quenched with 20 ml of aqueous sodium bisulfite solution (38-40%) and 30 ml of water. The organic phase is separated off and washed with 50 ml of sodium hydrogen carbonate solution and then with 50 ml of water. The organic phase is concentrated and purified by chromatography on silica gel using DCM / THF as the eluent, giving the desired compound.

Yield: 0.75 g (66%, mixture of diastereomers)

Preparation Example H1-6: Preparation of Compound 1-3

0343<chemistry id="chem0116" num="0116"><img file="EP3663366A2_D0116.tif" /></chemistry>

(1) Preparation of the precursor

V-1-3

or the active connection

1-9

0344<chemistry id="chem0117" num="0117"><img file="EP3663366A2_D0117.tif" /></chemistry>

034510.3 g of (R) -3-acetyl-5-methyl-furan-2,4-dione in 207 ml of toluene are placed in a reactor and successively with 7.5 g of trifluoroacetic acid and with 8.7 g of 1,2- Dihydroisoquinoline added. The mixture is heated to reflux for 24 h, cooled to room temperature and mixed with 67.5 ml of water and 4.2 ml of 50% NaOH. The resulting suspension is filtered and the filter cake is washed twice with 10 ml of toluene. The filter cake is dried in a stream of nitrogen, giving the desired compound.

Yield: 13 g (73%, HPLC: 98.9 FI%).

0346¹H-NMR (CDCl₃): m 7.20-7.39; q 5.50; q 5.39; m 5.14-5.22; m 5.06-5.14; d 3.98; m 3.78-3.86; m 3.42-3.58; m 3.23-3.41; m 3.00-3.13; m 2.86-3.00; m 2.42-2.72; d 1.50 [ppm]

(2) Preparation of Compound 1-3:

034710.8 g compound <b>V-1-3</b> are placed in 127 ml of toluene and 15.1 g of ethanedithiol and 22.9 g of trifluoroacetic acid are added in succession at room temperature. The mixture is stirred at room temperature for 40 h. Then 1.1 g of activated carbon are added, the mixture is stirred for one hour and filtered. 77 g of 10% sodium hydroxide solution are added to the filtrate. A festoff fails, which is filtered off. The solid is taken up in 51 ml of toluene and 51 ml of 1N NaOH, stirred at 0 ° C. for 30 min and filtered again. The filter cake is washed with toluene and MeOH and dried in a stream of nitrogen to give the desired compound.

Yield: 74% (HPLC purity: 97 FI%)

Preparation example H1-7: Preparation of compound 1-6

0348<chemistry id="chem0118" num="0118"><img file="EP3663366A2_D0118.tif" /></chemistry>

03497.7 g compound <b>V-1-3</b> are placed in 91 ml of toluene and mixed with 9.3 g of 1,3-propanedithiol. 16.4 g (0.143 mol) of trifluoroacetic acid are added and the mixture is stirred at RT for 24 h. 57 g of 10% NaOH are added. The precipitated solid is suctioned off. The aqueous phase is separated off from the filtrate and the organic phase is concentrated on a rotary evaporator. The residue is mixed with 51 ml of ethyl acetate, heated to reflux and then slowly cooled to 0 ° C. The mixture is stirred at 0 ° C for 30 min. The precipitated solid is filtered off, washed with ethyl acetate and dried in vacuo at 50 ° C.

0350100 ml of isopropanol are added to the solid and 70 ml of isopropanol are distilled off again through a Vigreux column. The suspension is cooled to 0 ° C. The solid is filtered off, washed with a little cold isopropanol and dried to obtain the desired compound.

Yield: 6.9 g (67%)

Preparation example H1-8: Preparation of compound 1-7

0351<chemistry id="chem0119" num="0119"><img file="EP3663366A2_D0119.tif" /></chemistry>

03521.0 g compound <b>1-3</b> in 4.5 ml of dichloromethane are introduced and a solution of 2.85 g of meta-chloroperbenzoic acid in 40 ml of dichloromethane is added within 50 min at 20-24 ° C. The mixture is stirred for 72 h and quenched with 20 ml of aqueous sodium bisulfite solution (38-40%) and 30 ml of water. The organic phase is separated off and washed successively with 50 ml of aqueous sodium hydrogen carbonate solution and 50 ml of water. The organic phase is concentrated and chromatographed over silica gel using DCM / THF as the eluent, giving the desired compound.

Yield: 0.88 g (74%)

<u>b) Production examples for connections according to structure type 2</u>

0353In principle, compounds of the formula II according to the invention are accessible from the amidine precursors C-II and enolates of the formula D-II and the resulting hydroxyl-functional compound B-II, which is then further converted to the desired end product.<chemistry id="chem0120" num="0120"><img file="EP3663366A2_D0120.tif" /></chemistry>

0354The various starting materials or intermediate compounds required for this are also known or can be obtained by known processes. (<nplcit id="ncit0056" npl-type="s"><text>Medwid et al., J. Med. Chem., 1990, 33 (4), 1230-1241</text></nplcit>), <nplcit id="ncit0057" npl-type="s"><text>Chesterfield et al., J. Chem. Soc., 1960, 4590-4594</text></nplcit>; <patcit id="pcit0075" dnum="EP407899B1"><text>W. Gienke et al, EP 407899B1</text></patcit>)

Production Example H2-1: Production of compound 2-1

0355<chemistry id="chem0121" num="0121"><img file="EP3663366A2_D0121.tif" /></chemistry>

(1) Preparation of precursor B-2-1

0356<chemistry id="chem0122" num="0122"><img file="EP3663366A2_D0122.tif" /></chemistry>

0357For the production of the amidine <b>C-2-1</b> Picolinitrile (90 mmol) is placed in methanol and 0.1 eq% sodium methylate (30% in MeOH) is added at room temperature. The mixture is stirred overnight at room temperature. 1.13 eq of ammonium chloride are added and the mixture is heated under reflux for 5 h.

0358For the production of the enolate <b>D-2-1</b> 23 g (2.23 eq) of potassium tert-butoxide are placed in THF and a solution of (11.9 g) 2.16 eq of methyl formate and 9.6 g (1.0 eq) of methyl methoxyacetate is added within 90 min . The mixture is stirred overnight at room temperature and 120 ml of THF are distilled off under vacuum. The amidinium salt is at 30-20 ° C within 30 min<b>2-C</b> closed in methanol. The mixture is stirred at 63 ° C for 5 h. It is cooled and hydrolyzed with water. It is distilled, the aqueous phase is adjusted to pH 4-5 with 32% aq. HCl and extracted with dichloromethane. The combined aqueous phases are concentrated on a rotary evaporator and the residue is extracted with diisopropyl ether. It is filtered and the crystals are dried in a stream of nitrogen, giving the desired compound.

Yield: 78%

03591H NMR (DMSO): d 8.71; d 8.25; tr 8.03; br s 7.68; m 7.56-7.63; s 3.84 [ppm]

(2) Preparation of precursor

A-2-1

0360<chemistry id="chem0123" num="0123"><img file="EP3663366A2_D0123.tif" /></chemistry>

03615 g (25 mmol) compound <b>B-2-1</b> are mixed with 40 g of phosphoryl chloride and the mixture is heated to reflux for 90 min. The excess POCl₃ is removed by distillation. It is cooled and dichloromethane is added to the residue. It is hydrolyzed with water and the batch is made basic with NaOH. The organic phase is separated off and the aqueous phase is extracted twice more with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered and evaporated on a rotary evaporator.

Yield: 94%

0362¹H-NMR (CDCl₃): d 8.82; s 8.47; d 8.42; tr 7.85; m 7.36-7.41; s 4.08 [ppm]

(3) Preparation of compound 2-1

0363<chemistry id="chem0124" num="0124"><img file="EP3663366A2_D0124.tif" /></chemistry>

036410.5 g (47 mmol) compound <b>A-2-1</b> are with 25 eq. Isopropylamine was added and the mixture was stirred at 32 ° C. overnight. Water and toluene are added and the phases are separated at 50 ° C. The aqueous phase is extracted twice with toluene and the combined organic phase is washed twice with a little water. The organic phase is dried over sodium sulfate, filtered and concentrated on a rotary evaporator. The product is recrystallized from MTBE to give the desired compound.

Yield: 78%

Preparation example H2-2: Preparation of compound 2-2

0365<chemistry id="chem0125" num="0125"><img file="EP3663366A2_D0125.tif" /></chemistry>

0366A solution of 4 g (47 mmol) of cyclopentylamine in 2-methyltetrahydrofuran is mixed with 5 g of compound <b>A-2-1</b> added and heated to reflux for 4 h. It is cooled to room temperature and the mixture is hydrolyzed. The aqueous phase is made basic with aqueous NaOH and the organic phase is separated off. The organic phase is washed again with water and then concentrated on a rotary evaporator. The crude product is chromatographed on silica gel, giving the desired compound.

Yield: 56%

Production Example H2-3: Production of compound 2-8

0367<chemistry id="chem0126" num="0126"><img file="EP3663366A2_D0126.tif" /></chemistry>

0368A solution of 1.7 g (19 mmol) of (S) -2-amino-3-methylbutane in 2-methyltetrahydrofuran is mixed with 2 g of compound <b>A-2-1</b> added and heated to reflux for 20 h. It is cooled to room temperature and the mixture is hydrolyzed. The aqueous phase is made basic with aqueous NaOH and the organic phase is separated off. The organic phase is washed again with water and then concentrated on a rotary evaporator. The crude product is chromatographed on silica gel, giving the desired compound.

Yield: 27%

Preparation example H2-4: Preparation of compound 2-5

0369<chemistry id="chem0127" num="0127"><img file="EP3663366A2_D0127.tif" /></chemistry>

0370A solution of 2.1 g (28.4 mmol) of (S) -2-aminobutane in 2-methyltetrahydrofuran is mixed with 3 g of compound <b>A-2-1</b> added and heated to reflux for 28 h. It is cooled to room temperature and the mixture is hydrolyzed. The aqueous phase is made basic with aqueous NaOH and the organic phase is separated off. The organic phase is washed once more with water and then concentrated on a rotary evaporator, giving the desired compound.

Yield: 92%

Preparation example H2-5: Preparation of compound 2-12

0371<chemistry id="chem0128" num="0128"><img file="EP3663366A2_D0128.tif" /></chemistry>

03721.0 g of potassium tert-butoxide and 28 ml of isopropanol are heated to 50 ° C. and with 2.0 g of compound <b>A-2-1</b> transferred. The heating is switched off and the mixture is stirred for 68 h. The batch is rotated in on a rotary evaporator and 50 g of water and 0.54 g of acetic acid are added. The aqueous phase is extracted twice with dichloromethane, the combined organic phases are evaporated in a rotary evaporator and the residue is crystallized from a mixture of 5 ml of MTBE and 15 ml of n-heptane. The crystals are filtered off with suction, washed with n-heptane and dried in a vacuum drying cabinet at 30 ° C., the desired compound being obtained.

Yield: 41% (HPLC purity: 100 FI%)

Preparation example H2-6: Preparation of compound 2-14

0373<chemistry id="chem0129" num="0129"><img file="EP3663366A2_D0129.tif" /></chemistry>

(1) Preparation of the precursor

B-2-2

0374<chemistry id="chem0130" num="0130"><img file="EP3663366A2_D0130.tif" /></chemistry>

0375For the production of the amidine <b>C-2-1</b> picolinitrile (90 mmol) is placed in methanol and 0.1 eq sodium methylate dissolved in methanol is added at room temperature. The mixture is stirred overnight at room temperature. 1.13 eq of ammonium chloride are added and the mixture is heated under reflux for 5 h.

0376For the production of the enolate <b>D-2-2</b> 12.8 g (2.23 eq) of potassium tert-butoxide are placed in THF and within 35 min at 18-22 ° C with a solution of 6.6 g (2.16 eq) of methyl formate and 5.9 g (1.0 eq) ethyl butyrate in 23.2 ml of THF. It is stirred overnight at room temperature and the mixture is spun in. At 10-20 ° C the amidinium salt<b>C-2-1</b> closed in methanol. The mixture is stirred at 63 ° C for 5 h. It is cooled and hydrolyzed with water. 100 ml of MTBE are added, the mixture is stirred briefly and the phases are separated. The organic phase is discarded and 6.5 ml of acetic acid are added to the aqueous phase. The aqueous phase is extracted three times with 67 ml dichloromethane each time. The organic phase is spun in and taken up again in MTBE. The MTBE phase is washed with water and mixed with 1.2 eq aqueous NaOH. The aqueous phase is separated off, brought to pH 7 with acetic acid and extracted with MTBE. The MTBE phase is dried over sodium sulfate, filtered and evaporated. It is crystallized from n-heptane.

Yield: 18.5% (HPLC purity: 100 FI%)

0377¹H-NMR (CDCl₃): 1br s 11.05; d 8.64; d 8.38; m 7.83-7.95; m 7.41-7.50; q 2.59; tr 1.25 [ppm]

(2) Preparation of precursor

A-2-2

0378<chemistry id="chem0131" num="0131"><img file="EP3663366A2_D0131.tif" /></chemistry>

03791.9 g compound <b>B-2-2</b> are dosed in 19 ml of phosphoryl chloride. The mixture is heated to reflux for 1 h. The excess phosphorus oxychloride is distilled off under vacuum and the residue is taken up in dichloromethane. 42 ml of water are added and the pH is adjusted to 7 with NaOH. The phases are separated and the organic phase over Na₂SO₄ dried. It is filtered and the filtrate is evaporated to give the desired compound.

Yield: 72% (HPLC purity: 100 FI%)

0380¹H-NMR (CDCl₃): d 8.84; s 8.70; d 8.48; tr 7.87; m 7.39-7.45; q 2.81; tr 1.33 [ppm]

(3) Preparation of compound 2-14

0381<chemistry id="chem0132" num="0132"><img file="EP3663366A2_D0132.tif" /></chemistry>

0382A mixture of 1.6 g (7.8 mmol) of 2-E and 11.04 g (187 mmol) of isopropylamine are stirred for 42 h at room temperature. The mixture is spun in and water, 1.33 eq NaOH and dichloromethane are added. The aqueous phase is separated off and extracted again with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered and evaporated. The residue is stirred with hot MTBE and the suspension is then cooled to room temperature. It is filtered, the residue washed with a little MTBE and dried at 50 ° C. in a vacuum drying cabinet, the desired compound being obtained.

Yield: 0.92 g (49%)

Preparation example H2-7: Preparation of compound 2-15

0383<chemistry id="chem0133" num="0133"><img file="EP3663366A2_D0133.tif" /></chemistry>

03840.865 g (4.5 mmol) citric acid and 1.11 g (4.09 mmol) compound <b>2-1</b> are mixed with 20 ml iPrOH and heated to reflux. It is cooled to 30 ° C and the precipitated crystals are suctioned off. The filter cake is washed with a little isopropanol and dried at 50 ° C. in a vacuum drying cabinet, the desired compound being obtained.

Yield: 1.74 g (97%)

Preparation Example H2-8: Preparation of Compound 2-16

0385<chemistry id="chem0134" num="0134"><img file="EP3663366A2_D0134.tif" /></chemistry>

03860.520 g (4.5 mmol) fumaric acid and 1.11 g (4.09 mmol) compound <b>2-1</b> are mixed with 20 ml iPrOH and heated to reflux. Sufficient water is added to create a clear solution. It is cooled to room temperature and the crystals which have precipitated are filtered off with suction. The filter cake is washed with a little iPrOH and MTBE and dried at 50 ° C. in a vacuum drying cabinet, giving the desired compound.

Yield: 0.88 g (60%)

Preparation Example H2-9: Preparation of Compound 2-17

0387<chemistry id="chem0135" num="0135"><img file="EP3663366A2_D0135.tif" /></chemistry>

03880.600 g (4.5 mmol) Äp rock acid and 1.1 g (4.1 mmol) compound<b>2-1</b> are mixed with 20 ml iPrOH and heated to reflux. Sufficient water is added to create a clear solution. It is cooled to room temperature and the crystals which have precipitated are filtered off with suction. The filter cake is washed with a little iPrOH and MTBE and dried at 50 ° C in a vacuum drying cabinet.

Weight: 0.77 g (50%)

Preparation example H2-10: Preparation of compound 2-18

0389<chemistry id="chem0136" num="0136"><img file="EP3663366A2_D0136.tif" /></chemistry>

03900.675 g (4.5 mmol) tartaric acid and 1.11 g (4.1 mmol) compound <b>2-1</b> are mixed with 20 ml iPrOH and heated to reflux. Sufficient water is added to create a clear solution. It is cooled to room temperature and the crystals which have precipitated are filtered off with suction. The filter cake is washed with a little iPrOH and MTBE and dried at 50 ° C. in a vacuum drying cabinet, giving the desired compound.

Yield: 1.32 g (85%)

Production Example H2-11: Production of compound 2-19

0391<chemistry id="chem0137" num="0137"><img file="EP3663366A2_D0137.tif" /></chemistry>

03920.675 g (5.7 mmol) succinic acid and 1.41 g (5.2 mmol) compound <b>2-1</b> are mixed with 26 ml iPrOH and heated to reflux. It is cooled to room temperature and the solution is spun in. The evaporated oil is stirred with 5 ml EtOAc and the crystals formed are suction filtered. The filter cake is washed with a little EtOAc and dried at 50 ° C. in a vacuum drying cabinet, the desired compound being obtained.

Yield: 0.77 g (41%)

Production Example H2-12: Production of compound 2-21

0393<chemistry id="chem0138" num="0138"><img file="EP3663366A2_D0138.tif" /></chemistry>

03941.1 g (4.3 mmol) of palmitic acid and 1.0 g (4.1 mmol) of compound <b>2-1</b> are mixed with 5 ml of heptane and heated to 50 ° C. It is cooled to 0 ° C and filtered. The crystals are filtered off with suction and dried in a vacuum drying cabinet, giving the desired compound.

Yield: 1.29 g (63%)

<u>c) Production examples for connections according to structure type 3</u>

0395The preparation of representative compounds of structure type 2 of the formula III is described in the following section. The various starting materials of the general formula C-III and B-III required for this are likewise known or can be obtained by known processes.<chemistry id="chem0139" num="0139"><img file="EP3663366A2_D0139.tif" /></chemistry>

0396The reaction is carried out, for example, in an apolar organic solvent in the presence of an acid scavenger.

Production Example H3-1: Production of (E) -N-cyclohexyl-N-pyridin-2-yl-3-m-tolyl-acrylamide, compound 3-31

0397<chemistry id="chem0140" num="0140"><img file="EP3663366A2_D0140.tif" /></chemistry>

03984.87 g (0.03 mol) of 3-methylcinnamic acid, 49 ml of toluene and 0.19 g (2.6 mmol) of N, N-dimethyformamide are initially introduced and 4.3 g (0.036 mol) of thionyl chloride are added. The mixture is stirred for 1 h and then heated to 60 ° C. Toluene and excess thionyl chloride are removed under vacuum. 24 ml of toluene and 4.3 g (0.033 mol) of ethyldiisopropylamine are then added at 60.degree. A solution of 5.8 g (0.033 mol) of cyclohexyl-2-pyridinylamine (preparation see<nplcit id="ncit0058" npl-type="s"><text> EH Mørkved, Journal f. practical chemistry, 1986, 328 (3), 401-406</text></nplcit>) metered in toluene and stirred at 60-65 ° C for 2 h. It is hydrolyzed with water and the organic phase is washed with water, 1 N NaOH and again with water. The organic phase is spun in and the residue is crystallized from MTBE. The crystallized solid is filtered off, washed with MTBE and dried, whereby the desired compound is obtained.

Yield: 74%

Preparation example H3-2: Preparation of (E) -3-benzo [1,3] dioxol-5-yl-N, N-diphenyl-acrylamide, compound 3-6

0399<chemistry id="chem0141" num="0141"><img file="EP3663366A2_D0141.tif" /></chemistry>

04004.8 g (0.025 mol) of 3,4-methylenedioxycinnamic acid, 48 ml of toluene and 0.16 g (2.16 mmol) of N, N-dimethylformamide are introduced, heated to 60 ° C. and at this temperature with 3.57 g (0.030 mol) thionyl chloride was added. The mixture is stirred at 60-65 ° C for 1.5 h. The mixture is then heated to boiling temperature and excess thionyl chloride and toluene are distilled off. At 60-65 ° C, 2.78 g of triethylamine and a solution of 4.2 g (0.025 mol) of diphenylamine in 24 ml of toluene are added in succession. The mixture is then stirred at 60-65 ° C for 16 h. It is hydrolyzed with water and, after phase separation, the organic phase is washed again with water at 60 ° C. It is filtered hot and evaporated. The residue is crystallized from isopropanol. The crystallized solid is filtered off at 0 ° C, washed with iPrOH and dried, whereby the desired compound is obtained.

Yield: 81%

Production Example H3-3: Production of (E) -N, N-dicyclohexyl-3- (4-methoxyphenyl) acrylamide, compound 3-18

0401<chemistry id="chem0142" num="0142"><img file="EP3663366A2_D0142.tif" /></chemistry>

04025.0 g (0.028 mol) of 3-methoxycinnamic acid, 50 ml of toluene and 0.23 g (3.0 mmol) of N, N-dimethylformamide are introduced and 4.01 g (0.034 mol) of thionyl chloride are added. It is stirred overnight. The mixture is then heated to 50 ° C. and excess thionyl chloride and toluene are distilled off under vacuum. Toluene and 4.0 g (0.031 mol) of diisopropylamine are added under normal pressure at 60 ° C. A solution of 5.6 g (0.031 mol) of dicyclohexylamine in toluene is then metered in. The mixture is stirred at 60 ° C for 30 min and cooled to RT. The reaction mixture is mixed with water and 2-methyltetrahydrofuran and heated to 70 ° C. After phase separation, the organic phase is washed twice with water, once with 1N sodium hydroxide solution and twice more with water at 50 ° C. The organic phase is spun in and recrystallized from n-heptane. The solid which has crystallized out is filtered off with suction at 0 ° C., washed with n-heptane and dried, the desired compound being obtained.

Yield: 50% (HPLC: 92 FI%)

Production Example H3-4: Production of (E) -3-benzo [1,3] dioxol-5-yl-N-cyclohexyl-N-isopropyl-acrylamide, compound 3-5

0403<chemistry id="chem0143" num="0143"><img file="EP3663366A2_D0143.tif" /></chemistry>

04045.77 g (0.030 mol) of trans-3,4- (methylenedioxy) cinnamic acid, 58 ml of toluene and 0.19 g (3.6 mmol) of N, N-dimethylformamide are initially charged and 4.28 g (0.036 mol ) Thionyl chloride added. The mixture is stirred at RT for 1 h. The mixture is then heated to 50-60 ° C and excess thionyl chloride and toluene are distilled off under vacuum. Toluene and 4.27 g (0.033 mol) of ethyldiisopropylamine are added under normal pressure at 60-70 ° C. A solution of 4.66 g (0.033 mol) of cyclohexyl isopropylamine in toluene is then metered in. The mixture is stirred at 60-70 ° C for 2 h and then hydrolyzed with water. After phase separation, the organic phase is washed at 50-70 ° C. with water, 2 N HCl, water, 1 N NaOH, water. The organic phase is spun in and recrystallized from iPrOH / n-heptane. The solid which has crystallized out is filtered off with suction at RT, washed with n-heptane and dried, the desired compound being obtained.

Yield: 46% (purity: 82%)

Production Example H3-5: Production of (E) -N-cyclohexyl-N-pyridin-2-yl-3-p-tolyl-acrylamide, compound 3-32

0405<chemistry id="chem0144" num="0144"><img file="EP3663366A2_D0144.tif" /></chemistry>

04065.50 g (0.034 mol) of 4-methylcinnamic acid, 61 ml of toluene and 0.27 g (3.7 mmol) of N, N-dimethyformamide are initially introduced and 4.8 g (0.041 mol) of thionyl chloride are added. The mixture is stirred for 1 h and then heated to 50 ° C. Toluene and excess thionyl chloride are removed under vacuum. 18 ml of toluene and 4.8 g (0.037 mol) of ethyldiisopropylamine are then added at 60.degree. A solution of 6.8 g (0.037 mol) of cyclohexyl-2-pyridylamine in toluene is metered in and the mixture is stirred at 60 ° C. for 1 h. It is hydrolyzed with water and 2-methyltetrahydrofuran is added. The organic phase is separated off and washed with water, 1 N NaOH and again with water. The organic phase is spun in and the residue is crystallized from MTBE. The crystallized solid is filtered off, washed with MTBE and dried, whereby the desired compound is obtained.

Yield: 62%

Production Example H3-6: Production of (E) -N-cyclohexyl-3, N-diphenyl-acrylamide, compound 3-26

0407<chemistry id="chem0145" num="0145"><img file="EP3663366A2_D0145.tif" /></chemistry>

04087.60 g (0.051 mol) of cinnamic acid, 92 ml of toluene and 0.41 g (5.6 mmol) of N, N-dimethyformamide are initially introduced and 7.3 g (0.062 mol) of thionyl chloride are added. The mixture is stirred for 1 h and then heated to 50 ° C. Toluene and excess thionyl chloride are removed under vacuum. 22 ml of toluene and 7.3 g (0.056 mol) of ethyldiisopropylamine are then added at 60 ° C. A solution of 9.1 g (0.056 mol) of N-cyclohexylaniline in toluene is metered in and the mixture is stirred at 60 ° C. for 1 h. It is hydrolyzed with water at 50 ° C. and 2-methyltetrahydrofuran is added. The organic phase is separated off and washed with water, 1N hydrochloric acid, 1N NaOH and again with water. The organic phase is spun in and the residue is crystallized from n-heptane / MTBE. The crystallized solid is filtered off, washed with n-heptane and dried, whereby the desired compound is obtained.

Yield: 68%

Preparation example H3-7: Preparation of (E) -3-benzo [1,3] dioxol-5-yl-N-cyclohexyl-N-pyridin-2-yl-acrylamide, compound 3-1

0409<chemistry id="chem0146" num="0146"><img file="EP3663366A2_D0146.tif" /></chemistry>

04105.18 g (0.027 mol) of trans-3,4- (methylenedioxy) cinnamic acid, 52 ml of toluene and 0.24 g (3.3 mmol) of N, N-dimethyformamide are initially charged and 3.85 g (0.032 mol) Thionyl chloride added. The mixture is stirred for 1.5 h and then heated to 50 ° C. Toluene and excess thionyl chloride are removed under vacuum. Then 18 ml of toluene and 3.83 g (0.030 mol) of ethyldiisopropylamine are added under normal pressure at 50-60 ° C. A solution of 5.2 g (0.030 mol) of N-cyclohexyl-2-pyridylamine in toluene is metered in and the mixture is stirred at 50-60 ° C. for 1 h. It is hydrolyzed with water at 50-60 ° C. The organic phase is separated off and washed with water, 1 N NaOH and again with water. The organic phase is filtered, evaporated and the residue is crystallized from toluene. The crystallized solid is filtered off at 0 ° C, washed with toluene and dried, whereby the desired compound is obtained.

Yield: 76%

<u>Formulation examples</u>

a) Oral care

Formulation example FM-1: mouthwash

0411Suitable mouthwashes can be produced according to the following basic recipe:<tables id="tabl0011" num="0011"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="21mm" /><colspec colnum="2" colname="col2" colwidth="33mm" /><colspec colnum="3" colname="col3" colwidth="81mm" /><thead><row><entry valign="top">% By weight</entry><entry valign="top">Ingredient type</entry><entry valign="top">Ingredient examples</entry></row></thead><tbody><row><entry>0,01-0,1%</entry><entry>antibacterial agents</entry><entry>beta-naphthol, thymol, chlorothymol and hexylresorcinol</entry></row><row><entry>5-25%</entry><entry>Humectant</entry><entry>Glycerin, sorbitol, propylene glycol and polyalkylene glycol</entry></row><row><entry>0,01-0,2%</entry><entry>essential oils</entry><entry>Clove oil, peppermint oil and spearmint oil</entry></row><row><entry>0-30%</entry><entry>Ethanol</entry><entry /></row><row><entry>0-5 %</entry><entry>polymer</entry><entry>Polyoxyalkylene block copolymers Mw 5000-30000</entry></row><row><entry>40-80%</entry><entry>water</entry><entry /></row><row><entry /><entry /><entry /></row><row><entry /><entry /><entry /></row><row><entry>0,001-10%</entry><entry>TRPM8 agonist</entry><entry /></row><row><entry>0-10%</entry><entry>Other additives</entry><entry /></row></tbody></tgroup></table></tables>

0412A mouthwash of the following composition is made:<tables id="tabl0012" num="0012"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="21mm" /><colspec colnum="2" colname="col2" colwidth="79mm" /><thead><row><entry valign="top">proportion of</entry><entry valign="top">ingredient</entry></row></thead><tbody><row><entry>177mL</entry><entry>Ethanol 95%</entry></row><row><entry>250 G</entry><entry>Sorbitol 70%</entry></row><row rowsep="0"><entry>50mL</entry><entry>TRPM8 agonist according to preparation example H 1-1 .....</entry></row><row><entry /><entry> as a 1% solution in ethanol</entry></row><row><entry>0.30 g</entry><entry>Peppermint oil,</entry></row><row><entry>0.64 g</entry><entry>Methyl salicylate</entry></row><row><entry>0.922 g</entry><entry>Eucalyptol</entry></row><row><entry>0.639 g</entry><entry>Thymol</entry></row><row><entry>1.50 g</entry><entry>Benzoic acid</entry></row><row rowsep="0"><entry>5.00 g</entry><entry>Pluronic ® F127</entry></row><row><entry /><entry> nonionic surfactant</entry></row><row><entry>0.60 g</entry><entry>Sodium saccharin</entry></row><row><entry>0.30 g</entry><entry>Sodium citrate</entry></row><row><entry>0.10 g</entry><entry>citric acid</entry></row><row><entry>qs 1 liter</entry><entry>water</entry></row></tbody></tgroup></table></tables>

0413To produce a mouthwash, the components described above are mixed together in the amounts specified.

Formulation example FM-2: toothpaste

0414Suitable toothpastes can be produced according to the following basic recipe:<tables id="tabl0013" num="0013"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="21mm" /><colspec colnum="2" colname="col2" colwidth="41mm" /><colspec colnum="3" colname="col3" colwidth="104mm" /><thead><row><entry valign="top">% By weight</entry><entry valign="top">Ingredient type</entry><entry valign="top">Ingredient examples</entry></row></thead><tbody><row><entry>0,05-0,2%</entry><entry>Fluorides</entry><entry>Sodium fluoride, tin (II) fluoride, sodium monofluorophosphate;</entry></row><row><entry>10-55%</entry><entry>Humectant</entry><entry>Glycerin, sorbitol, propylene glycol, polyalkylene glycol</entry></row><row><entry>0-50%</entry><entry>polymer</entry><entry>Polyoxyalkylene block copolymers Mw 5000-30000</entry></row><row><entry>10-50%</entry><entry>water</entry><entry /></row><row><entry>10-55%</entry><entry>Abrasives</entry><entry>Calcium pyrophosphate, dicalcium phosphate, silicon oxide hydrate;</entry></row><row><entry>2-10%</entry><entry>binder</entry><entry>Karaya gum, tragacanth USP, sodium alginate, Irish moss, methyl cellulose</entry></row><row><entry>2-8%</entry><entry>Surfactant</entry><entry>Sodium lauryl sulphate, sodium N-lauryl sarcosinate, dioctl sodium sulphosuccinate, sodium lauryl sulphoacetate</entry></row><row><entry>0-10%</entry><entry>Peroxygen compound</entry><entry>Hydrogen peroxide, inorganic peroxides</entry></row><row><entry>0,001-10%</entry><entry>TRPM8 agonist</entry><entry /></row><row><entry>0-10% like this</entry><entry>Other additives</entry><entry /></row></tbody></tgroup></table></tables>

Formulation example FM-3: chewing gum

0415Suitable chewing gum can be produced according to the following basic recipe:<tables id="tabl0014" num="0014"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="22mm" /><colspec colnum="2" colname="col2" colwidth="62mm" /><thead><row><entry valign="top">% By weight</entry><entry valign="top">ingredient</entry></row></thead><tbody><row><entry>15 - 25%</entry><entry>Chewing gum base ("gum base")</entry></row><row><entry>20 - 30%</entry><entry>Glucose syrup</entry></row><row><entry>50 - 60%</entry><entry>powdered sugar</entry></row><row><entry>0,001 - 10%</entry><entry>TRPM8 agonist according to example .H 2-1 ...</entry></row><row><entry>1 - 2%</entry><entry>Plasticizers (e.g. glycerin)</entry></row><row><entry>3 - 6%</entry><entry>water</entry></row></tbody></tgroup></table></tables>

0416Instead of glucose syrup and powdered sugar, the sugar alcohols mannitol, xylitol and sorbitol, "palatinite" and others as well as artificial sweeteners such as saccharin, cyclamate, acesulfame-K and aspartame can also be used for "sugar-free" recipes.

b) body care

Formulation example FK-1: hair tonic

0417<tables id="tabl0015" num="0015"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="118mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>qs</entry><entry>Perfume oil</entry></row><row><entry /><entry>1,00</entry><entry>PEG-40 Hydrogenated Castor Oil</entry></row><row><entry>B</entry><entry>65,0</entry><entry>alcohol</entry></row><row><entry /><entry>1,0</entry><entry>Panthenol</entry></row><row><entry /><entry>0,5</entry><entry>Polyquarternium-16</entry></row><row><entry /><entry>0,1</entry><entry>menthol</entry></row><row><entry /><entry>27,4</entry><entry>Aqua dem.</entry></row><row><entry /><entry>5,00</entry><entry>aqueous solution with approx. x 0.001-10%% TRPM8 agonist according to .example..H 3-1 ....</entry></row></tbody></tgroup></table></tables>

0418Preparation: Mix phase A. Add phase B and stir until everything is dissolved, adjust the pH to pH 7.0.

Formulation example FK-2: hair gel

0419<tables id="tabl0016" num="0016"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="110mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>45,00</entry><entry>Carbopol 940 1% in water</entry></row><row><entry /><entry>0,70</entry><entry>Aminomethyl propanol</entry></row><row><entry>B</entry><entry>7,50</entry><entry>VP / methacrylamide / vinyl imidazole copolymer</entry></row><row><entry /><entry>0,10</entry><entry>Perfume oil</entry></row><row><entry /><entry>0,30</entry><entry>PEG-40 Hydrogenated Castor Oil</entry></row><row><entry /><entry>0,30</entry><entry>Preservative</entry></row><row><entry /><entry>0,05</entry><entry>Disodium EDTA</entry></row><row><entry /><entry>0,30</entry><entry>Panthenol</entry></row><row><entry /><entry>8,00</entry><entry>Alcohol</entry></row><row><entry /><entry>5,00</entry><entry>aqueous solution with approx. 0.001-10% TRPM8 agonist according to example.H 1-3 ...</entry></row><row><entry /><entry>32,75</entry><entry>Aqua dem.</entry></row></tbody></tgroup></table></tables>

0420Production: Weigh in and homogenize the components of phase A. Dissolve phase B and stir into phase A. Adjust pH to pH 6.9.

Formulation example FK-3: Cosmetic sunscreen preparation

0421A cosmetic sun protection preparation containing a combination of at least inorganic pigment and organic UV filters is described in the following recipes.

0422The formulations mentioned below are prepared in a customary manner known to the person skilled in the art.<tables id="tabl0017" num="0017"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="30mm" colsep="0" /><colspec colnum="2" colname="col2" colwidth="38mm" /><colspec colnum="3" colname="col3" colwidth="98mm" /><tbody><row><entry>A</entry><entry>7.50 Uvinul MC 80</entry><entry>Ethylhexyl cinnamate</entry></row><row><entry /><entry>2.00 Uvinul M 40</entry><entry>Benzophenone-3</entry></row><row><entry /><entry>0.80 Rylo PG 11</entry><entry>Polyglyceryl dimersoyate</entry></row><row><entry /><entry>1.00 Span 60</entry><entry>Sorbitan stearate</entry></row><row><entry /><entry>0.50 vitamin E acetate</entry><entry>Tocopheryl acetate</entry></row><row><entry /><entry>3.00 Dracorin 100 SE</entry><entry>Glyceryl stearate, PEG-100 stearate</entry></row><row><entry /><entry>1.00 Cremophor CO 410</entry><entry>PEG-40 hydrogenated castor oil</entry></row><row><entry>B</entry><entry>3.00 T-Lite SF</entry><entry>Titanium dioxide, aluminum oxide hydrate, dimethicone / methicone copolymer</entry></row><row><entry /><entry>1.00 Cetiol SB 45</entry><entry><i>Butyrospermum parkii</i> (Shea butter)</entry></row><row><entry /><entry>6.50 Finsolv TN</entry><entry>C._12-15Alkyl benzoate</entry></row><row><entry>C.</entry><entry>5.00 butylene glycol</entry><entry>Butylene glycol</entry></row><row><entry /><entry>0.30 Keltrol</entry><entry>Xanthan gum</entry></row><row><entry /><entry>0.10 Edeta BD</entry><entry>Disodium EDTA</entry></row><row><entry /><entry>0.10 allantoin</entry><entry>Allantoin</entry></row><row><entry /><entry>66.20 water dem.</entry><entry>Aqua dem.</entry></row><row><entry>D</entry><entry>1.00 Sepigel 305</entry><entry>Polyacrylamide, C_13-14-Isoparaffin, Laureth-7</entry></row><row><entry namest="col1" nameend="col2" align="left">0.001-10% TRPM8 agonist according to the example. H2-3</entry><entry /></row><row><entry /><entry>qs</entry><entry>Preservative</entry></row></tbody></tgroup></table></tables>

Formulation example FK-4: Moisturizing body care cream

0423<tables id="tabl0018" num="0018"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="104mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>6,0</entry><entry>PEG-7 hydrogenated castor oil</entry></row><row><entry /><entry>10,0</entry><entry>Cetearyl ethyl hexanoate</entry></row><row><entry /><entry>5,0</entry><entry>Isopropyl myristate</entry></row><row><entry /><entry>7,0</entry><entry>mineral oil</entry></row><row><entry /><entry>0,5</entry><entry>Shea Butter (<i>Butyrospermum parkii</i>)</entry></row><row><entry /><entry>0,5</entry><entry>Aluminum stearate</entry></row><row><entry /><entry>0,5</entry><entry>Magnesium stearate</entry></row><row><entry /><entry>0,2</entry><entry>Bisabolol</entry></row><row><entry /><entry>0,7</entry><entry>Quaternium-18 hectorite</entry></row><row><entry>B</entry><entry>5,0</entry><entry>Dipropylene glycol</entry></row><row><entry /><entry>0,7</entry><entry>Magnesium sulfate</entry></row><row><entry /><entry>qs</entry><entry>Preservative</entry></row><row><entry /><entry>62,9</entry><entry>Aqua dem.</entry></row><row><entry /><entry>qs</entry><entry>Perfume oil</entry></row><row><entry>C.</entry><entry>1,0</entry><entry>aqueous solution with 0.001-10% TRPM8 agonist according to example H 3-2 ...</entry></row></tbody></tgroup></table></tables>

0424Production: Heat phases A and B separately to approx. 80 ° C. Stir phase B into phase A and homogenize. Cool with stirring to approx. 40 ° C, add phase C and homogenize again. Allow to cool to room temperature while stirring.

Formulation example FK-5: care shampoo

0425<tables id="tabl0019" num="0019"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="105mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>30,0</entry><entry>Sodium laureth sulfate</entry></row><row><entry /><entry>6,0</entry><entry>Sodium cocoamphoacetate</entry></row><row><entry /><entry>6,0</entry><entry>Cocamidopropyl betaine</entry></row><row><entry /><entry>3,0</entry><entry>Sodium laureth sulfate, glycol distearate, cocamide MEA, Laureth-10</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to example H 1-6 ...</entry></row><row><entry /><entry>7,7</entry><entry>Polyquaternium-44</entry></row><row><entry /><entry>2,0</entry><entry>Amodimethicone</entry></row><row><entry /><entry>qs</entry><entry>Perfume oil</entry></row><row><entry /><entry>qs</entry><entry>Preservative</entry></row><row><entry /><entry>1,0</entry><entry>Sodium chloride</entry></row><row><entry /><entry>43,3</entry><entry>Aqua dem.</entry></row><row><entry>B</entry><entry>qs</entry><entry>citric acid</entry></row></tbody></tgroup></table></tables>

0426Preparation: Mix and dissolve the phase A components. Adjust the pH to 6-7 with citric acid.

Formulation example FK-6: shower gel

0427<tables id="tabl0020" num="0020"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="106mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>40,0</entry><entry>Sodium laureth sulfate</entry></row><row><entry /><entry>5,0</entry><entry>Decyl glucoside</entry></row><row><entry /><entry>5,0</entry><entry>Cocamidopropyl betaine</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to example H 2-5 ...</entry></row><row><entry /><entry>1,0</entry><entry>Panthenol</entry></row><row><entry /><entry>qs</entry><entry>Perfume oil</entry></row><row><entry /><entry>qs</entry><entry>Preservative</entry></row><row><entry /><entry>2,0</entry><entry>Sodium chloride</entry></row><row><entry /><entry>46,0</entry><entry>Aqua dem.</entry></row><row><entry>B</entry><entry>qs</entry><entry>citric acid</entry></row></tbody></tgroup></table></tables>

0428Preparation: Mix and dissolve the phase A components. Adjust the pH to 6-7 with citric acid.

Formulation example FK-7: shampoo

0429<tables id="tabl0021" num="0021"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="93mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>40,0</entry><entry>Sodium laureth sulfate</entry></row><row><entry /><entry>5,0</entry><entry>Sodium-C_12-15-Pareth-15 sulfonate</entry></row><row><entry /><entry>5,0</entry><entry>Decyl glucoside</entry></row><row><entry /><entry>qs</entry><entry>Perfume oil</entry></row><row><entry /><entry>0,1</entry><entry>Phytantriol</entry></row><row><entry /><entry>44,6</entry><entry>Aqua dem.</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 -10% TRPM8 agonist according to H 2-7 ...</entry></row><row><entry /><entry>0,3</entry><entry>Polyquaternium-10</entry></row><row><entry /><entry>1,0</entry><entry>Panthenol</entry></row><row><entry /><entry>qs</entry><entry>Preservative</entry></row><row><entry /><entry>1,0</entry><entry>Laureth-3</entry></row><row><entry /><entry>2,0</entry><entry>Sodium chloride</entry></row></tbody></tgroup></table></tables>

0430Preparation: Mix and dissolve the phase A components. Adjust the pH to 6-7 with citric acid.

Formulation example FK-8: foot balm

0431<tables id="tabl0022" num="0022"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="93mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>2,0</entry><entry>Ceteareth-6, stearyl alcohol</entry></row><row><entry /><entry>2,0</entry><entry>Ceteareth-25</entry></row><row><entry /><entry>5,0</entry><entry>Cetearyl ethyl hexanoate</entry></row><row><entry /><entry>4,0</entry><entry>Cetyl alcohol</entry></row><row><entry /><entry>4,0</entry><entry>Glyceryl stearate</entry></row><row><entry /><entry>5,0</entry><entry>mineral oil</entry></row><row><entry /><entry>0,2</entry><entry>menthol</entry></row><row><entry /><entry>0,5</entry><entry>Fighter</entry></row><row><entry>B</entry><entry>69,3</entry><entry>Aqua dem.</entry></row><row><entry /><entry>qs</entry><entry>Preservative</entry></row><row><entry>C.</entry><entry>1,0</entry><entry>Bisabolol</entry></row><row><entry /><entry>1,0</entry><entry>Tocopheryl acetate</entry></row><row><entry>D</entry><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to H 3-3 ...</entry></row><row><entry /><entry>5,0</entry><entry>Witch hazel extract</entry></row></tbody></tgroup></table></tables>

0432Production: Heat the components of phases A and B separately to approx. 80 ° C. Stir phase B into phase A with homogenization. Cool with stirring to approx. 40 ° C, add phases C and D and briefly homogenize. Cool to room temperature with stirring.

Formulation example FK-9: Facial cleansing lotion - type O / W

0433<tables id="tabl0023" num="0023"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="94mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>10,0</entry><entry>Cetearyl ethyl hexanoate</entry></row><row><entry /><entry>10,0</entry><entry>Caprylic / capric triglyceride</entry></row><row><entry /><entry>1,5</entry><entry>Cyclopentasiloxane, cyclohexasilosane</entry></row><row><entry /><entry>2,0</entry><entry>PEG-40 hydrogenated castor oil</entry></row><row><entry>B</entry><entry>3,5</entry><entry>Caprylic / capric triglyceride, sodium acrylate copolymer</entry></row><row><entry>C.</entry><entry>1,0</entry><entry>Tocopheryl acetate</entry></row><row><entry /><entry>0,2</entry><entry>Bisabolol</entry></row><row><entry /><entry>qs</entry><entry>Preservative</entry></row><row><entry /><entry>qs</entry><entry>Perfume oil</entry></row><row><entry>D</entry><entry>3,0</entry><entry>Polyquaternium-44</entry></row><row><entry /><entry>0,5</entry><entry>Cocotrimonium methosulfate</entry></row><row><entry /><entry>0,5</entry><entry>Ceteareth-25</entry></row><row><entry /><entry>2,0</entry><entry>Panthenol, propylene glycol</entry></row><row><entry /><entry>4,0</entry><entry>Propylene glycol</entry></row><row><entry /><entry>0,1</entry><entry>Disodium EDT A</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to H 3-4 ...</entry></row><row><entry /><entry>60,7</entry><entry>Aqua dem.</entry></row></tbody></tgroup></table></tables>

0434Preparation: Solve phase A. Stir phase B into phase A, incorporate phase C into the combined phases A and B. Dissolve phase D, stir into the combined phases A, B and C and homogenize. Stir for 15 minutes.

Formulation example FK-10: body spray

0435<tables id="tabl0024" num="0024"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="93mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>3,0</entry><entry>Ethylhexyl methoxycinnamate</entry></row><row><entry /><entry>2,0</entry><entry>Diethylaminohydroxybenzoylhexylbenzoate</entry></row><row><entry /><entry>1,0</entry><entry>Polyquaternium-44</entry></row><row><entry /><entry>3,0</entry><entry>Propylene glycol</entry></row><row><entry /><entry>2,0</entry><entry>Panthenol, propylene glycol</entry></row><row><entry /><entry>1,0</entry><entry>Cyclopentasiloxane, cyclohexasilosane</entry></row><row><entry /><entry>10,0</entry><entry>Octyldodecanol</entry></row><row><entry /><entry>0,5</entry><entry>PVP</entry></row><row><entry /><entry>10,0</entry><entry>Caprylic / capric triglyceride</entry></row><row><entry /><entry>3,0</entry><entry>C._12-15Alkyl benzoate</entry></row><row><entry /><entry>3,0</entry><entry>Glycerin</entry></row><row><entry /><entry>1,0</entry><entry>Tocopheryl acetate</entry></row><row><entry /><entry>0,3</entry><entry>Bisabolol</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to H 2-4 ...</entry></row><row><entry /><entry>59,2</entry><entry>alcohol</entry></row></tbody></tgroup></table></tables>

0436Production: Weigh in the components of phase A and dissolve clearly.

Formulation example FK-11: skin care gel

0437<tables id="tabl0025" num="0025"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="94mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>3,6</entry><entry>PEG-40 hydrogenated castor oil</entry></row><row><entry /><entry>15,0</entry><entry>alcohol</entry></row><row><entry /><entry>0,1</entry><entry>Bisabolol</entry></row><row><entry /><entry>0,5</entry><entry>Tocopheryl acetate</entry></row><row><entry /><entry>qs</entry><entry>Perfume oil</entry></row><row><entry>B</entry><entry>3,0</entry><entry>Panthenol</entry></row><row><entry /><entry>0,6</entry><entry>Carbomer</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to H 3-5 ...</entry></row><row><entry /><entry>75,4</entry><entry>Aqua dem.</entry></row><row><entry>C.</entry><entry>0,8</entry><entry>Triethanolamine</entry></row></tbody></tgroup></table></tables>

Formulation example FK-12: after-shave lotion

0438<tables id="tabl0026" num="0026"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="94mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>10,0</entry><entry>Cetearyl ethyl hexanoate</entry></row><row><entry /><entry>5,0</entry><entry>Tocopheryl acetate</entry></row><row><entry /><entry>1,0</entry><entry>Bisabolol</entry></row><row><entry /><entry>0,1</entry><entry>Perfume oil</entry></row><row><entry /><entry>0,3</entry><entry>Acrylates / C_10-30 Alkyl acrylate cross polymer</entry></row><row><entry>B</entry><entry>15,0</entry><entry>alcohol</entry></row><row><entry /><entry>1,0</entry><entry>Panthenol</entry></row><row><entry /><entry>3,0</entry><entry>Glycerin</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to ... H 2-7</entry></row><row><entry /><entry>0,1</entry><entry>Triethanolamine</entry></row><row><entry /><entry>63,5</entry><entry>Aqua dem.</entry></row></tbody></tgroup></table></tables>

0439Preparation: Mix the components of phase A. Solve phase B, work into phase A and homogenize.

Formulation example FK-13: after-sun lotion

0440<tables id="tabl0027" num="0027"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="93mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>0,4</entry><entry>Acrylate / C10-30 alkyl acrylate cross polymer</entry></row><row><entry /><entry>15,0</entry><entry>Cetearyl ethyl hexanoate</entry></row><row><entry /><entry>0,2</entry><entry>Bisabolol</entry></row><row><entry /><entry>1,0</entry><entry>Tocopheryl acetate</entry></row><row><entry /><entry>qs</entry><entry>Perfume oil</entry></row><row><entry>B</entry><entry>1,0</entry><entry>Panthenol</entry></row><row><entry /><entry>15,0</entry><entry>alcohol</entry></row><row><entry /><entry>3,0</entry><entry>Glycerin</entry></row><row><entry /><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to H 3-6 ...</entry></row><row><entry /><entry>63,2</entry><entry>Aqua dem.</entry></row><row><entry>C.</entry><entry>0,2</entry><entry>Triethanolamine</entry></row></tbody></tgroup></table></tables>

0441Preparation: Mix the components of phase A. Stir phase B into phase A with homogenization. Neutralize with phase C and homogenize again.

Formulation example FK-14: sun protection lotion

0442<tables id="tabl0028" num="0028"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="8mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="137mm" /><thead><row><entry valign="top" /><entry valign="top">%</entry><entry valign="top">Ingredient (INCI)</entry></row></thead><tbody><row><entry>A</entry><entry>4,5</entry><entry>Ethylhexyl methoxycinnamate</entry></row><row><entry /><entry>2,0</entry><entry>Diethylaminohydroxybenzoylhexylbenzoate</entry></row><row><entry /><entry>3,0</entry><entry>Octocrylene</entry></row><row><entry /><entry>2,5</entry><entry>Di-C12-13 alkyl malate</entry></row><row><entry /><entry>0,5</entry><entry>Tocopheryl acetate</entry></row><row><entry /><entry>4,0</entry><entry>Polyglyceryl-3-methylglucose distearate</entry></row><row><entry>B</entry><entry>3,5</entry><entry>Cetearyl isononanoate</entry></row><row><entry /><entry>1,0</entry><entry>VP / eicose copolymer</entry></row><row><entry /><entry>5,0</entry><entry>Isohexadecane</entry></row><row><entry /><entry>2,5</entry><entry>Di-C12-13 alkyl malate</entry></row><row><entry /><entry>3,0</entry><entry>Titanium dioxide, trimethoxycaprylylsilane</entry></row><row><entry>C.</entry><entry>5,0</entry><entry>Glycerin</entry></row><row><entry /><entry>1,0</entry><entry>Sodium cetearyl sulfate</entry></row><row><entry /><entry>0,5</entry><entry>Xanthan gum</entry></row><row><entry /><entry>59,7</entry><entry>Aqua dem.</entry></row><row><entry>D</entry><entry>1,0</entry><entry>aqueous solution with 0.001 - 10% TRPM8 agonist according to H 2-9 ...</entry></row><row><entry /><entry>1,0</entry><entry>Phenoxyethanol, methyl paraben, ethyl paraben, butyl paraben, propyl paraben, isobutyl paraben</entry></row><row><entry /><entry>0,3</entry><entry>Bisabolol</entry></row></tbody></tgroup></table></tables>

0443Production: Heat the components of phases A and B separately to approx. 80 ° C. Stir phase B into phase A and homogenize. Heat phase C to approx. 80 ° C and stir into the combined phases A and B while homogenizing. Cool with stirring to approx. 40 ° C, add phase D and homogenize again.

Formulation example FK-15: plasters

044450 Parts of active ingredient according to Preparation Example H 3-7 were dispersed in 100 parts of a 10% sodium lauryl sulfate solution with vigorous stirring and heating to 50 ° C. 880 parts of a 50% butyl acrylate dispersion were stirred into the resulting emulsion and the polymer dispersion obtained with the active ingredient was obtained by means of a suitable doctor blade on a polyester film with a thickness of 15 μm (Fa. Kalle, D-Wiesbaden) and dried at 35 to 40 ° C under controlled humidity. Depending on the doctor blade setting, basis weights of 5 mg / cm resulted²which could be further increased through multiple orders. The self-adhesive film thus produced with an active ingredient content of 5% was provided with a siliconized release film made of polyester (Scotch Pak 75 μm, 3M) and cut into the desired dimensions.

0445The quantities given relate to parts by weight.

c) food

Formulation example FN-1: pudding

Recipe (for 100 ml)

0446<tables id="tabl0029" num="0029"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="66mm" /><colspec colnum="2" colname="col2" colwidth="17mm" /><thead><row><entry valign="top">ingredient</entry><entry valign="top">amount</entry></row></thead><tbody><row><entry>Fat-free dry milk</entry><entry>10.715 g</entry></row><row><entry>Sucrose</entry><entry>5 G</entry></row><row><entry>Novel strength, National Starch</entry><entry>7 G</entry></row><row><entry>Vegetable oil mixture</entry><entry>2.2 g</entry></row><row><entry>Carrageenan</entry><entry>0.016 g</entry></row><row><entry>Vanilla flavor</entry><entry>0.5 g</entry></row><row><entry>Sodium stearoyl-2-lactylate</entry><entry>0.095 g</entry></row><row><entry>Yellow dye</entry><entry>0.189 g</entry></row><row><entry>Magnesium phosphate</entry><entry>0.165 g</entry></row><row><entry>Vitamin premix</entry><entry>1.84 g</entry></row><row><entry>Trace element premix</entry><entry>0.015 g</entry></row><row><entry>Active ingredient according to preparation example H 2-11</entry><entry>0.5 g</entry></row><row><entry>water</entry><entry>81.94 g</entry></row></tbody></tgroup></table></tables>

Manufacturing:

0447Heat nine tenths of the water to 43.3 ° C. Dissolve skim milk powder in the water. Heat the oil to 60 ° C and add carrageenan and oil-soluble vitamins to the oil. Mix oil into the product. Add the remaining ingredients apart from the modified starch, vanilla flavor and vitamin premix. Homogenize the mixture. Add starch slowly. Add active ingredient, vitamins and aroma. Standardize solids content. Heat in sterile units and pack in cans.

d) Formulation example FT-1: textile finishing with active substances according to the invention

0448An aqueous slurry of amylose-containing starch is first prepared by adding 5 g of deionized water to 10 g of a commercially available preservative. 20 g of carboxymethyl cellulose were dissolved therein, then 400 g of an amylose-containing starch with an amylose content of 50% by weight were added and a slurry was prepared with stirring.

0449Aqueous liquors containing amylose-containing starch are then produced using one of the following two methods:<ul id="ul0023" list-style="none"><li>Method 1: The respective slurry is adjusted to a starch content of 5 or 15% by weight by dilution with water.</li><li>Method 2: The respective slurry is first diluted with water to a starch content of 5 or 15% by weight and then mixed with 30 g / l of a 30% by weight aqueous polyurethane dispersion (non-ionic).</li></ul>

0450A fabric is then finished with amylose-containing starch and the active ingredient according to the invention: Cotton fabric pattern with a basis weight of 124 g / m² is treated with one of the above-made liquors by means of a padder up to a liquor absorption of 80% by weight, based on the weight of the fabric. The mixture is then dried at 120 ° C. for 2 minutes.

0451Subsequently, the fabric samples treated in this way are treated with an aqueous active ingredient formulation by applying an aqueous emulsion / suspension of an active ingredient according to the invention with an active ingredient content of 1 to 7% by weight to a liquor absorption of 79-80% by weight on the fabric sample lined up. The fabric samples treated in this way are then dried in a household dryer to a residual moisture of 15%.

0452The active substance-laden tissues produced in this way can then be examined further, for example for their cooling effect on skin contact or their repellent effect on insects.

Examples, especially regarding the special aspect of the invention (Chapter 6.)

0453The examples SX listed below relate in particular to the special aspect of the invention (chapter 6). However, they are not limited to these and can also serve to explain the general aspect of the invention. Conversely, the examples denoted by SX are not the exclusive examples for the special aspect of the invention (chapter 6), but the examples described above can of course also be used to explain the special aspect of the invention. Accordingly, the compounds to be used according to the special aspect of the invention (compounds from Table 0) are also referred to as compounds according to the invention in the examples below.

Example S-1

0454Production of flavors with a cooling effect of the eucalyptus menthol type using the cooling substances according to the invention: The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0030" num="0030"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="74mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><thead><row><entry><b>approach</b></entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row><row><entry><b>component</b></entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></thead><tbody><row><entry valign="bottom">Anethole</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Peppermint oil Mentha piperita, type Willamette</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry></row><row><entry valign="bottom">Peppermint oil Mentha arvensis, rectified</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry></row><row><entry valign="bottom"><i>I.</i>Menthyl lactate</entry><entry valign="bottom">1</entry><entry valign="bottom">1</entry><entry valign="bottom">1</entry><entry valign="bottom">1</entry><entry valign="bottom">1</entry><entry valign="bottom">1</entry><entry valign="bottom">1</entry><entry valign="bottom">1</entry></row><row><entry valign="bottom">2-hydroxyethyl methyl carbonate</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry></row><row><entry valign="bottom">2-hydroxypropyl menthyl carbonate</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry></row><row><entry valign="bottom">1,8-cineol (eucalyptol)</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry></row><row><entry valign="bottom"><i>I.</i>-Menthol</entry><entry valign="bottom">39,4</entry><entry valign="bottom">39,5</entry><entry valign="bottom">39,7</entry><entry valign="bottom">39,7</entry><entry valign="bottom">39,8</entry><entry valign="bottom">39,4</entry><entry valign="bottom">39,5</entry><entry valign="bottom">39,4</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom">0,6</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethylspiro [4b-azachrysen-12.2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethylspiro [4b-azachrysen-12.2 '- [1,3] dithian] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Cyclopentyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /></row><row><entry valign="bottom">Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom">0,6</entry></row><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Total</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry></row></tbody></tgroup></table></tables>

0455The flavors obtained in this way were incorporated into a standard toothpaste paste based on silica in a concentration of 1.2% by weight. The toothpastes were tested by a sensor-trained expert panel under practical conditions. The sensory evaluations showed: very beautiful, rich and voluminous minty freshness with a comparatively quick, strong and pronounced and comparatively long-lasting cooling freshness impression, whereby it was striking that the sensation of cold was quickly perceptible in the entire mouth. In addition, the aroma was assessed as softer and more neutral and less pungent than without the compounds according to the invention. If, instead of the compounds according to the invention, an equal amount of 3-menthane carboxylic acid-N-ethylamide ("WS-3"), which is generally regarded as the standard cooling substance, was used, it was found that the cooling freshness impression was not as strong, not so voluminous and not felt so long.

Example S-2

0456Production of flavors with a cooling effect from the Krausminz type using the cooling substances according to the invention.

0457The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0031" num="0031"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="71mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="11mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><thead><row><entry valign="top">approach</entry><entry valign="top">a</entry><entry valign="top">b</entry><entry valign="top">c</entry><entry valign="top">d</entry><entry valign="top">e</entry><entry valign="top">f</entry><entry valign="top">G</entry><entry valign="top">H</entry></row><row><entry valign="top"><b>component</b></entry><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /></row></thead><tbody><row><entry>menthol</entry><entry>29,25</entry><entry>29,25</entry><entry>29</entry><entry>29,6</entry><entry>29,6</entry><entry>29,5</entry><entry>29,2</entry><entry>29,5</entry></row><row><entry>Carvon</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry></row><row><entry>Spearmint oil, type Native</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry></row><row><entry>Anethole</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry></row><row><entry>Peppermint oil rectha arvensis rectified</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry></row><row><entry>Peppermint oil Mentha piperita, type Willamette</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry></row><row><entry>3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry>0,75</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry /><entry>0,75</entry><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>4-methoxycinnamic acid-N, N-diphenylamide</entry><entry /><entry /><entry>1</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry valign="middle">2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle">0,4</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle">0,2</entry></row><row><entry valign="middle">2,3,4,5,6,10b, 11,12-octahydro-3-methyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle">0,4</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /></row><row><entry valign="middle">5,6,10b, 11-tetrahydro-3-methyl-spiro [12H-benzo [a] furo [3,4-f] quinolizine-12,2 '- [1,3] dithiolan] -1 (3H) on</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle">0,5</entry><entry valign="middle" /><entry valign="middle" /></row><row><entry>Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>0,6</entry><entry /></row><row><entry>Cyclobutyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amines</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>0,2</entry><entry>0,3</entry></row><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Total</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry></row></tbody></tgroup></table></tables>

0458The aromas obtained were incorporated at a concentration of 1.2% into a toothpaste mass, which consists of 65% sodium bicarbonate. The toothpastes were tested under practical conditions and assessed by a sensor-trained expert panel. In each case, a beautiful, strong, spicy mint taste was found in connection with a voluminous and long-lasting cooling, fresh taste.

Example S-3

0459Production of aromas with a cooling effect and a spicy-aromatic taste impression using the cooling substances according to the invention.

0460The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0032" num="0032"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="76mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="11mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="11mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="11mm" /><thead><row><entry>approach</entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row><row><entry>component</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></thead><tbody><row><entry valign="bottom"><i>I.</i>-Menthol</entry><entry valign="bottom">29,2</entry><entry valign="bottom">29</entry><entry valign="bottom">29,5</entry><entry valign="bottom">29,4</entry><entry valign="bottom">29,4</entry><entry valign="bottom">29</entry><entry valign="bottom">29,3</entry><entry valign="bottom">29</entry></row><row><entry valign="bottom">Peppermint oil Mentha arvensis, rectified</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry></row><row><entry valign="bottom">Peppermint oil Mentha piperita, type Willamette</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry></row><row><entry valign="bottom">Anethole</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Spearmint oil, type Native</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Cinnamaldehyde</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry></row><row><entry valign="bottom">Eugenol</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom">0,8</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">4-methylcinnamic acid-N, N-diphenylamide</entry><entry valign="bottom" /><entry valign="bottom">1</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3-methyl-spiro [4b-azachrysen-12,2 '- [1,3] dithian] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,4</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) -isopropyl-amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,7</entry><entry valign="bottom" /><entry valign="bottom">1</entry></row><row><entry valign="bottom">sec-butyl- (5-methoxy-2-pyridin-2-ylpyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Cyclopentyl- (5-ethyl-2-pyridin-2-ylpyrimidin-4-yl) amines</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /></row><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Total</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry></row></tbody></tgroup></table></tables>

0461The flavors obtained in this way were each incorporated into a standard toothpaste mass based on silica in a concentration of 1.2% by weight. The toothpastes were tested by a sensor-trained expert panel under practical conditions. The sensory evaluation showed: very beautiful, minty, aromatic-spicy freshness with a very strong and pronounced, very long-lasting cooling freshness impression.

Example S-4

0462Production of aromas with cooling effect and wintergreen taste using the cooling substances according to the invention: The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0033" num="0033"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="70mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><thead><row><entry>approach</entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row><row><entry>component</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></thead><tbody><row><entry valign="bottom">Anethole</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Peppermint oil Mentha arvensis</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry></row><row><entry valign="bottom">Peppermint oil Mentha piperita, type Willamette</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry><entry valign="bottom">12</entry></row><row><entry valign="bottom">Methyl salicylate</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry></row><row><entry valign="bottom">I-menthol</entry><entry valign="bottom">40,5</entry><entry valign="bottom">40,25</entry><entry valign="bottom">40,25</entry><entry valign="bottom">40,5</entry><entry valign="bottom">40,5</entry><entry valign="bottom">40,4</entry><entry valign="bottom">40,5</entry><entry valign="bottom">40,4</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /></row><row><entry valign="bottom">4-methoxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom" /><entry valign="bottom">0,75</entry><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Cinnamic acid-N, N-diphenylamide</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,25</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithian] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,4</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-aza-chrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom">0,1</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) -isopropyl-amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,4</entry><entry valign="bottom">0,6</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">(1,2-dimethyl-propyl) - (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /></row><row><entry valign="bottom">Cyclopentyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,6</entry></row><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Total</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry></row></tbody></tgroup></table></tables>

0463The flavors obtained in this way were incorporated into a standard toothpaste paste based on silica in a concentration of 1.2% by weight. The toothpastes were tested by a sensor-trained expert panel under practical conditions. The sensory evaluation showed in each case: pronounced fresh-minty winter green note, with a very strong and pronounced, very long-lasting cooling freshness impression.

Example S-5

0464Production of aromas with a cooling effect and peppermint taste using the cooling substances according to the invention: The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0034" num="0034"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="78mm" /><colspec colnum="2" colname="col2" colwidth="11mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="11mm" /><colspec colnum="7" colname="col7" colwidth="11mm" /><colspec colnum="8" colname="col8" colwidth="11mm" /><colspec colnum="9" colname="col9" colwidth="11mm" /><thead><row><entry>approach</entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row><row><entry>component</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></thead><tbody><row><entry valign="bottom">Peppermint oil Mentha arvensis</entry><entry valign="bottom">59</entry><entry valign="bottom">59,2</entry><entry valign="bottom">59,5</entry><entry valign="bottom">59,5</entry><entry valign="bottom">59</entry><entry valign="bottom">59</entry><entry valign="bottom">59</entry><entry valign="bottom">59</entry></row><row><entry valign="bottom">I-Menthon</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry></row><row><entry valign="bottom">I-menthol</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom">1</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom" /><entry valign="bottom">0,8</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3-methyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-aza-chrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,8</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry></row><row><entry valign="bottom">sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Cyclopentyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,8</entry><entry valign="bottom">0,5</entry></row><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Total</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry></row></tbody></tgroup></table></tables>

0465The flavors thus obtained were each incorporated into a sugar-free standard chewing gum mass in a concentration of 1.5% by weight. The chewing gums were tested for their sensory quality by a trained panel of experts. It was found that by adding the substances according to the invention the flavors contain a pronounced fresh note, which enhances the peppermint taste and provides a long-lasting feeling of freshness, which is clearly perceived for a long time even after the chewing gum has been chewed.

Example S-6

0466Production of aromas with a cooling effect and spearmint flavor using the cooling substances according to the invention: The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0035" num="0035"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="74mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><thead><row><entry>approach</entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row><row><entry>component</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></thead><tbody><row><entry valign="bottom">Peppermint oil Mentha piperita, type Madras</entry><entry valign="bottom">50</entry><entry valign="bottom">50,3</entry><entry valign="bottom">50,3</entry><entry valign="bottom">51</entry><entry valign="bottom">50,5</entry><entry valign="bottom">51</entry><entry valign="bottom">50</entry><entry valign="bottom">50</entry></row><row><entry valign="bottom">Eucalyptol</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry><entry valign="bottom">20</entry></row><row><entry valign="bottom">I-menthol</entry><entry valign="bottom">13,5</entry><entry valign="bottom">13,5</entry><entry valign="bottom">13,5</entry><entry valign="bottom">13,5</entry><entry valign="bottom">13,5</entry><entry valign="bottom">13,5</entry><entry valign="bottom">13,5</entry><entry valign="bottom">13,5</entry></row><row><entry valign="bottom">I-Menthon</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Spearmint oil, type Midwest Scotch</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry></row><row><entry valign="bottom">4-methylcinnamic acid N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom">1,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">4-methoxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom" /><entry valign="bottom">0,6</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,8</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Cinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom" /><entry valign="bottom">0,6</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-aza-chrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-aza-chrysen-12,2 '- [1,3] dithian] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1,2</entry><entry valign="bottom" /></row><row><entry valign="bottom">sec-butyl- (5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom">0,5</entry></row><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Total</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry></row></tbody></tgroup></table></tables>

0467The flavors thus obtained were each incorporated into a sugar-free standard chewing gum mass in a concentration of 1.5% by weight. The chewing gums were tested for their sensory quality by a trained panel of experts. It was found that the flavors obtained a pronounced fresh note through the addition of the substances according to the invention, which harmonized very well with the typical spearmint taste and provided for a pronounced, long-lasting feeling of freshness, which was clearly perceptible for a long time even after chewing the chewing gum stops.

Example S-7

0468Production of aromas with a cooling effect and an aromatic-spicy cinnamon taste using the cooling substances according to the invention: The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0036" num="0036"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="76mm" /><colspec colnum="2" colname="col2" colwidth="11mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="11mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="11mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><thead><row><entry>approach</entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row><row><entry>component</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></thead><tbody><row><entry valign="bottom">Menthyl methyl ether</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry></row><row><entry valign="bottom">Cinnamaldehyde</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Anethole</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Eugenol</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry></row><row><entry valign="bottom">Peppermint oil Mentha piperita, type Madras</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Peppermint oil mentha arvensis</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">Spearmint oil, type Midwest Scotch</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry><entry valign="bottom">10</entry></row><row><entry valign="bottom">I-menthol</entry><entry valign="bottom">40</entry><entry valign="bottom">39,8</entry><entry valign="bottom">40,4</entry><entry valign="bottom">40,4</entry><entry valign="bottom">41</entry><entry valign="bottom">40,5</entry><entry valign="bottom">40</entry><entry valign="bottom">40,2</entry></row><row><entry valign="bottom">2-hydroxyethyl methyl carbonate</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry></row><row><entry valign="bottom">2-hydroxypropyl methyl carbonate</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry></row><row><entry valign="bottom">Cinnamic acid-N, N-diphenylamide</entry><entry valign="bottom" /><entry valign="bottom">0,6</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">4-methoxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom" /><entry valign="bottom">0,6</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom">1</entry><entry valign="bottom" /><entry valign="bottom">0,4</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry></row><row><entry valign="bottom">5,6,10b, 11-tetrahydro-3-methylspiro [12H-benzo [a] furo [3,4-f] quinolizine-12,2 '- [1,3] dithian] -1 (3H) on</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithian] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one (</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom">0,2</entry></row><row><entry valign="bottom">Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1</entry><entry valign="bottom" /></row><row><entry valign="bottom">Cyclobutyl- (5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry></row><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Total</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry></row></tbody></tgroup></table></tables>

0469The flavors thus obtained were each incorporated into a sugar-free standard chewing gum mass in a concentration of 1.5% by weight. The chewing gums were tested for their sensory quality by a trained panel of experts. It was found that the aromas obtained a pronounced fresh note by the addition of the cooling substances according to the invention, which harmonizes very well with the spicy-aromatic taste and ensures a rapid onset of perceptible and long-lasting sensation of freshness in the entire mouth, which also after chewing the Chewing gums can still be clearly perceived for a long time. Overall, the aroma is more harmonious and significantly less pungent due to the addition of cooling substances according to the invention.

Example S-8

0470Production of mouthwash flavors with cooling effect using the cooling substances according to the invention: The following were mixed (all data, unless otherwise noted, in% by weight):<tables id="tabl0037" num="0037"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="74mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><thead><row><entry>approach</entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row><row><entry>component</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></thead><tbody><row><entry valign="bottom">Anethole</entry><entry valign="bottom">30</entry><entry valign="bottom">30</entry><entry valign="bottom">30</entry><entry valign="bottom">30</entry><entry valign="bottom">30</entry><entry valign="bottom">30</entry><entry valign="bottom">30</entry><entry valign="bottom">30</entry></row><row><entry valign="bottom">Eucalyptol</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry><entry valign="bottom">25</entry></row><row><entry valign="bottom">l-menthol</entry><entry valign="bottom">44,4</entry><entry valign="bottom">44,2</entry><entry valign="bottom">44,9</entry><entry valign="bottom">44,8</entry><entry valign="bottom">44,4</entry><entry valign="bottom">44,5</entry><entry valign="bottom">44,4</entry><entry valign="bottom">44,4</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom">0,6</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,4</entry><entry valign="bottom" /></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom" /><entry valign="bottom">0,8</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,4</entry></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom">0,1</entry><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom">0,1</entry><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,6</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,1</entry><entry valign="bottom" /></row><row><entry valign="bottom">sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom">0,2</entry></row><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Total</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry><entry valign="bottom">100</entry></row></tbody></tgroup></table></tables>

0471The flavors were each incorporated into a ready-to-use mouthwash at a concentration of 0.15% by weight, or into a mouthwash concentrate at a concentration of 3% by weight. The sensory evaluation by a trained panel of experts showed that the aromas led to a quick-acting, very long-lasting freshness effect that lasted for almost 1 hour after using the mouthwash.

0472The aroma compositions mentioned under Examples S-1 to S-8 are suitable for use in a whole range of different finished products, the use not being restricted to toothpastes only. In all of the examples listed below, an advantageous, fast-starting, but at the same time very long-lasting feeling of freshness was perceived without this freshness impression being impaired by sharp and bitter notes.

0473Below are further application examples for the above-mentioned aroma compositions in other finished products:

Example S-9

Toothpaste ('Silica opaque')

0474Unless otherwise noted, all data in% by weight.<tables id="tabl0038" num="0038"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="73mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Deionized water</entry><entry>26,53</entry><entry>26,53</entry><entry>26,53</entry><entry>26,53</entry><entry>26,53</entry><entry>26,53</entry></row><row><entry>Sorbitol 70%</entry><entry>45</entry><entry>Ad 100</entry><entry>45</entry><entry>Ad 100</entry><entry>45</entry><entry>Ad 100</entry></row><row><entry>Solbrol M Na salt</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry></row><row><entry>Trisodium phosphate</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>Saccharin</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Sodium monofluorophosphate</entry><entry>1,12</entry><entry>1,12</entry><entry>1,12</entry><entry>1,12</entry><entry>1,12</entry><entry>1,12</entry></row><row><entry>PEG 1500</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry></row><row><entry>Sident 9 (abrasive silica)</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry></row><row><entry>Sident 22 S (Thickening Silica)</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry></row><row><entry>Sodium carboxymethyl cellulose</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry></row><row><entry>Titanium (IV) oxide</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Sodium Lauryl Sulfate (SLS)</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry></row><row><entry>PLM pellitor solution (containing 10% pellitor)</entry><entry>-</entry><entry>0,025</entry><entry>-</entry><entry>0,025</entry><entry>-</entry><entry>0,025</entry></row><row><entry>Aroma type eucalyptus menthol (example S-1b)</entry><entry>1</entry><entry>1</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1c)</entry><entry /><entry /><entry>1</entry><entry>1</entry><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1f)</entry><entry /><entry /><entry /><entry /><entry>1</entry><entry>1</entry></row></tbody></tgroup></table></tables>

Example S-10

Toothpaste (calcium carbonate base)

0475Unless otherwise noted, all data in% by weight.<tables id="tabl0039" num="0039"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="73mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Deionized water</entry><entry>27,5</entry><entry>Ad 100</entry><entry>27,5</entry><entry>Ad 100</entry><entry>27,5</entry><entry>Ad 100</entry></row><row><entry>Saccharin</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Solbrol M sodium salt</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Sodium monofluorophosphate</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry></row><row><entry>Sorbitol 70%</entry><entry>29</entry><entry>29</entry><entry>29</entry><entry>29</entry><entry>29</entry><entry>29</entry></row><row><entry>Calcium carbonate</entry><entry>35</entry><entry>35</entry><entry>35</entry><entry>35</entry><entry>35</entry><entry>35</entry></row><row><entry>Sident 22 S (thickening silica)</entry><entry>2,5</entry><entry>2,5</entry><entry>2,5</entry><entry>2,5</entry><entry>2,5</entry><entry>2,5</entry></row><row><entry>Sodium carboxymethyl cellulose</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry></row><row><entry>Titanium dioxide</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Sodium lauryl sulfate</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry></row><row><entry>PLM pellitor solution (containing 10% pellitor)</entry><entry>-</entry><entry>0,02</entry><entry>-</entry><entry>0,02</entry><entry>-</entry><entry>0,02</entry></row><row><entry>Aroma type eucalyptus menthol (example S-1a)</entry><entry>1</entry><entry>1</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1d)</entry><entry /><entry /><entry>1</entry><entry>1</entry><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1h)</entry><entry /><entry /><entry /><entry /><entry>1</entry><entry>1</entry></row></tbody></tgroup></table></tables>

Example S-11

Toothpaste with bleaching effect

0476Unless otherwise noted, all data in% by weight.<tables id="tabl0040" num="0040"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="69mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Polyphosphate (Glass H, (n ≈ 21), Astaris)</entry><entry>7</entry><entry>7</entry><entry>7</entry><entry>7</entry><entry>7</entry><entry>7</entry></row><row><entry>Calcium peroxide</entry><entry>1</entry><entry>-</entry><entry>2,5</entry><entry>1</entry><entry>-</entry><entry>2,5</entry></row><row><entry>Na percarbonate</entry><entry>-</entry><entry>11</entry><entry>-</entry><entry>-</entry><entry>11</entry><entry>-</entry></row><row><entry>Poloxamer 407</entry><entry>5</entry><entry>2</entry><entry>5</entry><entry>5</entry><entry>2</entry><entry>5</entry></row><row><entry>Polyethylene glycol</entry><entry>3</entry><entry>-</entry><entry>3</entry><entry>3</entry><entry>-</entry><entry>3</entry></row><row><entry>Sorbitol, 70% in water</entry><entry>-</entry><entry>22</entry><entry>-</entry><entry>-</entry><entry>22</entry><entry>-</entry></row><row><entry>Glycerin</entry><entry>43,8</entry><entry>12,5</entry><entry>28,6</entry><entry>43,8</entry><entry>12,5</entry><entry>28,6</entry></row><row><entry>1,2-propylene glycol</entry><entry>4</entry><entry>-</entry><entry>2,5</entry><entry>4</entry><entry>-</entry><entry>2,5</entry></row><row><entry>Na saccharin</entry><entry>0,4</entry><entry>0,2</entry><entry>0,5</entry><entry>0,4</entry><entry>0,2</entry><entry>0,5</entry></row><row><entry>Sodium bicarbonate</entry><entry>-</entry><entry>5</entry><entry>15</entry><entry>-</entry><entry>5</entry><entry>15</entry></row><row><entry>sodium</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry></row><row><entry>Silica</entry><entry>20</entry><entry>22</entry><entry>20</entry><entry>20</entry><entry>22</entry><entry>20</entry></row><row><entry>Na carboxymethyl cellulose</entry><entry>0,6</entry><entry>0,55</entry><entry>0,3</entry><entry>0,6</entry><entry>0,55</entry><entry>0,3</entry></row><row><entry>Sodium lauryl sulfate</entry><entry>1</entry><entry>4</entry><entry>2</entry><entry>1</entry><entry>4</entry><entry>2</entry></row><row><entry>Xanthan gum</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Titanium dioxide (anatase)</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Aroma type eucalyptus menthol (example S-1d)</entry><entry>1</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1g)</entry><entry /><entry /><entry /><entry>1</entry><entry /><entry /></row><row><entry>Aroma type spicy-aromatic (example S-3a)</entry><entry /><entry>1,25</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma type spicy-aromatic (example S-3d)</entry><entry /><entry /><entry /><entry /><entry>1,25</entry><entry /></row><row><entry>Aroma type spicy-aromatic (example S-3e)</entry><entry /><entry /><entry>1,5</entry><entry /><entry /><entry /></row><row><entry>Aroma type spicy-aromatic (example S-3g)</entry><entry /><entry /><entry /><entry /><entry /><entry>1,5</entry></row><row><entry>Distilled water</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry></row></tbody></tgroup></table></tables>

Example S-12

Toothpastes with tin and zinc salts

0477Unless otherwise noted, all data in% by weight.<tables id="tabl0041" num="0041"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="71mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry>Sodium fluoride NaF</entry><entry>0,42</entry><entry>0,5</entry><entry>-</entry><entry>0,42</entry><entry>0,5</entry><entry>-</entry></row><row><entry>Tin fluoride SnF2</entry><entry>-</entry><entry>0,9</entry><entry>0,95</entry><entry>-</entry><entry>0,9</entry><entry>0,95</entry></row><row><entry>Tin chloride SnCl2</entry><entry>1,5</entry><entry>-</entry><entry>2</entry><entry>1,5</entry><entry>-</entry><entry>2</entry></row><row><entry>Zinc lactate</entry><entry>2</entry><entry>2</entry><entry>-</entry><entry>2</entry><entry>2</entry><entry>-</entry></row><row><entry>Zinc carbonate ZnCO3</entry><entry>-</entry><entry>1</entry><entry>1,5</entry><entry>-</entry><entry>1</entry><entry>1,5</entry></row><row><entry>Na gluconate</entry><entry>-</entry><entry>0,67</entry><entry>1,5</entry><entry>-</entry><entry>0,67</entry><entry>1,5</entry></row><row><entry>Poloxamer 407</entry><entry>14,5</entry><entry>-</entry><entry>-</entry><entry>14,5</entry><entry>-</entry><entry>-</entry></row><row><entry>Polyethylene glycol</entry><entry>1</entry><entry>3</entry><entry>-</entry><entry>1</entry><entry>3</entry><entry>-</entry></row><row><entry>Sorbitol, 70% in water</entry><entry>-</entry><entry>38</entry><entry>37,5</entry><entry>-</entry><entry>38</entry><entry>37,5</entry></row><row><entry>Glycerin</entry><entry>37,5</entry><entry>5</entry><entry>14,4</entry><entry>37,5</entry><entry>5</entry><entry>14,4</entry></row><row><entry>1,2-propylene glycol</entry><entry>7</entry><entry>5</entry><entry>-</entry><entry>7</entry><entry>5</entry><entry>-</entry></row><row><entry>Na saccharin</entry><entry>0,3</entry><entry>0,5</entry><entry>0,5</entry><entry>0,3</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Abrasive silica</entry><entry>20</entry><entry>22,5</entry><entry>25</entry><entry>20</entry><entry>22,5</entry><entry>25</entry></row><row><entry>Sodium hydroxide</entry><entry>-</entry><entry>0,1</entry><entry>0,2</entry><entry>-</entry><entry>0,1</entry><entry>0,2</entry></row><row><entry>Sodium lauryl sulfate</entry><entry>-</entry><entry>2</entry><entry>1,5</entry><entry>-</entry><entry>2</entry><entry>1,5</entry></row><row><entry>Na polyphosphate</entry><entry>-</entry><entry>-</entry><entry>4</entry><entry>-</entry><entry>-</entry><entry>4</entry></row><row><entry>Tetrasodium pyrophosphate</entry><entry>1</entry><entry>2,5</entry><entry>-</entry><entry>1</entry><entry>2,5</entry><entry>-</entry></row><row><entry>Dye (1% in water)</entry><entry>0,4</entry><entry>0,5</entry><entry>0,5</entry><entry>0,4</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Aroma eucalyptus menthol type (example S-1b)</entry><entry>0,95</entry><entry>-</entry><entry>-</entry><entry /><entry>-</entry><entry>-</entry></row><row><entry>Aroma eucalyptus menthol type (example S-1c)</entry><entry /><entry /><entry /><entry>0,95</entry><entry /><entry /></row><row><entry>Aroma type spicy-aromatic (example S-3c)</entry><entry>-</entry><entry>1,2</entry><entry>-</entry><entry>-</entry><entry /><entry>-</entry></row><row><entry>Aroma type spicy-aromatic (example S-3f)</entry><entry /><entry /><entry /><entry /><entry>1,2</entry><entry /></row><row><entry>Aroma type wintergreen (example S-4a)</entry><entry>-</entry><entry>-</entry><entry>1,15</entry><entry>-</entry><entry>-</entry><entry /></row><row><entry>Aroma type wintergreen (example S-4e)</entry><entry /><entry /><entry /><entry /><entry /><entry>1,15</entry></row><row><entry>Distilled water</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry></row></tbody></tgroup></table></tables>

Example S-13

Phosphate-based toothpaste

0478Unless otherwise noted, all data in% by weight.<tables id="tabl0042" num="0042"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="60mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top" /><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row><row><entry valign="top">component</entry><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /></row></thead><tbody><row><entry>Deionized water</entry><entry>36,39</entry><entry>36,39</entry><entry>36,59</entry><entry>36,59</entry><entry>36,39</entry><entry>36,39</entry></row><row><entry>Glycerin</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry></row><row><entry>Solbrol M (sodium salt)</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry></row><row><entry>Sodium monofluorophosphate</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry></row><row><entry>Saccharin</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Dicalcium phosphate dihydrate</entry><entry>36</entry><entry>36</entry><entry>36</entry><entry>36</entry><entry>36</entry><entry>36</entry></row><row><entry>Aerosil® 200 (silica)</entry><entry>3</entry><entry>3</entry><entry>3</entry><entry>3</entry><entry>3</entry><entry>3</entry></row><row><entry>Sodium carboxymethyl cellulose</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry></row><row><entry>Sodium lauryl sulfate (Texapon)</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry><entry>1,3</entry></row><row><entry>Flavor type spearmint (example S-2a)</entry><entry>1</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Flavor type spearmint (example S-2b)</entry><entry /><entry>1</entry><entry /><entry /><entry /><entry /></row><row><entry>Flavor type spearmint (example S-2d)</entry><entry /><entry /><entry>0,8</entry><entry /><entry /><entry /></row><row><entry>Flavor type spearmint (example S-2f)</entry><entry /><entry /><entry /><entry>0,8</entry><entry /><entry /></row><row><entry>Flavor type spearmint (example S-2g)</entry><entry /><entry /><entry /><entry /><entry>1</entry><entry /></row><row><entry>Flavor type spearmint (example S-2h)</entry><entry /><entry /><entry /><entry /><entry /><entry>1</entry></row></tbody></tgroup></table></tables>

Example S-14

Toothpaste (transparent gel formulation)

0479Unless otherwise noted, all data in% by weight.<tables id="tabl0043" num="0043"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="87mm" /><colspec colnum="2" colname="col2" colwidth="13mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="13mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="13mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Sorbitol 70%</entry><entry>63</entry><entry>Ad 100</entry><entry>63</entry><entry>Ad 100</entry><entry>63</entry><entry>Ad 100</entry></row><row><entry>Deionized water</entry><entry>11,31</entry><entry>11,31</entry><entry>11,31</entry><entry>11,31</entry><entry>11,31</entry><entry>11,31</entry></row><row><entry>Saccharin</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Sodium monofluorophosphate</entry><entry>1,14</entry><entry>1,14</entry><entry>1,14</entry><entry>1,14</entry><entry>1,14</entry><entry>1,14</entry></row><row><entry>Solbrol</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry></row><row><entry>Trisodium phosphate</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>PEG 1500 (PEG 32)</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry></row><row><entry>Sident 9 (abrasive silica)</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry></row><row><entry>Sident 22 S (thickening silica)</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry><entry>8</entry></row><row><entry>Sodium carboxymethyl cellulose</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry></row><row><entry>Sodium lauryl sulfate</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry></row><row><entry>PLM pellitor solution (containing 10% pellitor)</entry><entry>-</entry><entry>0,025</entry><entry>-</entry><entry>0,025</entry><entry>-</entry><entry>0,025</entry></row><row><entry>Aroma type spicy-aromatic (menthol cinnamon) (example S-3c)</entry><entry>1</entry><entry>-</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma type spicy-aromatic (menthol cinnamon) (example S-3e)</entry><entry /><entry>1</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma type spicy-aromatic (menthol cinnamon) (example S-3h)</entry><entry /><entry /><entry>1</entry><entry /><entry /><entry /></row><row><entry>Aroma type wintergreen (example S-4b)</entry><entry>-</entry><entry /><entry /><entry>1</entry><entry /><entry /></row><row><entry>Aroma type wintergreen (example S-4d)</entry><entry /><entry /><entry /><entry /><entry>1</entry><entry /></row><row><entry>Aroma type wintergreen (example S-4g)</entry><entry /><entry /><entry /><entry /><entry /><entry>1</entry></row></tbody></tgroup></table></tables>

Example S-15

Mouthwash concentrate with aroma of the winter green type

0480Unless otherwise noted, all data in% by weight.<tables id="tabl0044" num="0044"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="57mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Ethyl alcohol 96%</entry><entry>42</entry><entry>42</entry><entry>42</entry><entry>42</entry><entry>42</entry><entry>42</entry></row><row><entry>Cremophor RH 455</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry></row><row><entry>Deionized water</entry><entry>48,67</entry><entry>48,67</entry><entry>50,67</entry><entry>49,67</entry><entry>48,67</entry><entry>48,67</entry></row><row><entry>Allantoin</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Sodium saccharin 450</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>Color L-Blue 5000 (1% in water)</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry></row><row><entry>Aroma type wintergreen (example S-4b)</entry><entry>4</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry valign="bottom">Aroma type wintergreen (example S-4c)</entry><entry valign="bottom" /><entry valign="bottom">4</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Aroma type wintergreen (example S-4d)</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Aroma type wintergreen (example S-4e)</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">3</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Aroma type wintergreen (example S-4f)</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">4</entry><entry valign="bottom" /></row><row><entry valign="bottom">Aroma type wintergreen (example S-4h)</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">4</entry></row></tbody></tgroup></table></tables>

Example S-16

Mouthwash ('ready to use' without alcohol)

0481Unless otherwise noted, all data in% by weight.<tables id="tabl0045" num="0045"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="73mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Cremophor RH 455</entry><entry>1,8</entry><entry>1,8</entry><entry>1,8</entry><entry>1,8</entry><entry>1,8</entry><entry>1,8</entry></row><row><entry>Deionized water</entry><entry>87,57</entry><entry>Ad 100</entry><entry>87,57</entry><entry>Ad 100</entry><entry>87,57</entry><entry>Ad 100</entry></row><row><entry>Sorbitol 70%</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry><entry>10</entry></row><row><entry>Sodium fluoride</entry><entry>0,18</entry><entry>0,18</entry><entry>0,18</entry><entry>0,18</entry><entry>0,18</entry><entry>0,18</entry></row><row><entry>Sodium saccharin 450</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>Solbrol M sodium salt</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry></row><row><entry>PLM pellitor solution (containing 10% pellitor)</entry><entry>-</entry><entry>0,0125</entry><entry>-</entry><entry>0,0125</entry><entry>-</entry><entry>0,0125</entry></row><row><entry>Mouthwash aroma (example S-8a)</entry><entry>0,2</entry><entry>0,2</entry><entry /><entry /><entry /><entry /></row><row><entry>Mouthwash aroma (example S-8d)</entry><entry /><entry /><entry>0,2</entry><entry>0,2</entry><entry /><entry /></row><row><entry>Mouthwash aroma (example S-8g)</entry><entry /><entry /><entry /><entry /><entry>0,2</entry><entry>0,2</entry></row></tbody></tgroup></table></tables>

Example S-17

Mouthwash ('ready to use' with alcohol)

0482Unless otherwise noted, all data in% by weight.<tables id="tabl0046" num="0046"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="65mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Ethyl alcohol 96%</entry><entry>10</entry><entry>5</entry><entry>7</entry><entry>10</entry><entry>5</entry><entry>7</entry></row><row><entry>Cremophor CO 40</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry></row><row><entry>Benzoic acid</entry><entry>0,1</entry><entry>0,12</entry><entry>0,1</entry><entry>0,1</entry><entry>0,12</entry><entry>0,1</entry></row><row><entry>Deionized water</entry><entry>83,46</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>83,46</entry><entry>Ad 100</entry><entry>Ad 100</entry></row><row><entry>Sorbitol 70%</entry><entry>5</entry><entry>1</entry><entry>5</entry><entry>5</entry><entry>1</entry><entry>5</entry></row><row><entry>Sodium saccharin 450</entry><entry>0,07</entry><entry>0,05</entry><entry>0,05</entry><entry>0,07</entry><entry>0,05</entry><entry>0,05</entry></row><row><entry>L-Blue 5000 (1% in water)</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>Glycerin</entry><entry>-</entry><entry>8</entry><entry>-</entry><entry>-</entry><entry>8</entry><entry>-</entry></row><row><entry>1,2-propylene glycol</entry><entry>-</entry><entry>2</entry><entry>3</entry><entry>-</entry><entry>2</entry><entry>3</entry></row><row><entry>Cetylpyridinium chloride</entry><entry>-</entry><entry>-</entry><entry>0,07</entry><entry>-</entry><entry>-</entry><entry>0,07</entry></row><row><entry>Hydrogen peroxide (35% H2O2 in water)</entry><entry>-</entry><entry>3</entry><entry>4</entry><entry>-</entry><entry>3</entry><entry>4</entry></row><row><entry>Aroma wintergreen (example S-4d)</entry><entry>0,25</entry><entry>-</entry><entry>-</entry><entry /><entry>-</entry><entry>-</entry></row><row><entry>Aroma wintergreen (example S-4h)</entry><entry /><entry /><entry /><entry>0,25</entry><entry /><entry /></row><row><entry>Mouthwash aroma (example S-8b)</entry><entry>-</entry><entry>0,25</entry><entry>0,25</entry><entry /><entry /><entry /></row><row><entry>Mouthwash aroma (example S-8c)</entry><entry /><entry /><entry /><entry /><entry>0,25</entry><entry>0,25</entry></row></tbody></tgroup></table></tables>

Example S-18

Toothpaste and mouthwash as a 2-in-1 product

0483Unless otherwise noted, all data in% by weight.<tables id="tabl0047" num="0047"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="69mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Ethanol, 96%</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry></row><row><entry>Sorbitol, 70% in water</entry><entry>40</entry><entry>40</entry><entry>40</entry><entry>40</entry><entry>40</entry><entry>40</entry></row><row><entry>Glycerin</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry></row><row><entry>Saccharin</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Na monofluorophosphate</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry><entry>0,76</entry></row><row><entry>Solbrol M, Na salt</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry><entry>0,15</entry></row><row><entry>Abrasive silica (Sident 9)</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry></row><row><entry>Thickening silica (Sident 22S)</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry></row><row><entry>Na carboxymethyl cellulose loose</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry></row><row><entry>Sodium lauryl sulfate</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry><entry>1,2</entry></row><row><entry>Green dye (1% in water)</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Aroma type eucalyptus menthol (example S-1a)</entry><entry>1</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1b)</entry><entry /><entry>1</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1c)</entry><entry /><entry /><entry>1</entry><entry /><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1e)</entry><entry /><entry /><entry /><entry>1</entry><entry /><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1f)</entry><entry /><entry /><entry /><entry /><entry>1</entry><entry /></row><row><entry>Aroma type eucalyptus menthol (example S-1h)</entry><entry /><entry /><entry /><entry /><entry /><entry>1</entry></row><row><entry>Distilled water</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry></row></tbody></tgroup></table></tables>

Example S-19

Standard chewing gum

0484Unless otherwise noted, all data in% by weight.<tables id="tabl0048" num="0048"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="74mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="10mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="10mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry>Gum base</entry><entry>21</entry><entry>21</entry><entry>21</entry><entry>21</entry><entry>21</entry><entry>21</entry></row><row><entry>Glucose syrup</entry><entry>16,5</entry><entry>17</entry><entry>16,5</entry><entry>16,5</entry><entry>17</entry><entry>16,5</entry></row><row><entry>Glycerin</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Powdered sugar</entry><entry>60</entry><entry>60</entry><entry>60</entry><entry>60</entry><entry>60</entry><entry>60</entry></row><row><entry>Aroma eucalyptus type peppermint (example S-5b)</entry><entry>2</entry><entry>-</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma eucalyptus type peppermint (example S-5c)</entry><entry /><entry>1,5</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma eucalyptus type peppermint (example S-5h)</entry><entry /><entry /><entry>2</entry><entry /><entry /><entry /></row><row><entry>Flavor type mint (example S-6c)</entry><entry>-</entry><entry /><entry /><entry>2</entry><entry /><entry /></row><row><entry>Flavor type mint (example S-6d)</entry><entry /><entry /><entry /><entry /><entry>1,5</entry><entry /></row><row><entry>Flavor type mint (example S-6g)</entry><entry /><entry /><entry /><entry /><entry /><entry>2</entry></row></tbody></tgroup></table></tables>

Example S-20

Sugar-free chewing gum

0485Unless otherwise noted, all data in% by weight.<tables id="tabl0049" num="0049"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="96mm" /><colspec colnum="2" colname="col2" colwidth="9mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="11mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="9mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Gum base</entry><entry>30</entry><entry>30</entry><entry>30</entry><entry>30</entry><entry>30</entry><entry>30</entry></row><row><entry>Sorbitol powdered</entry><entry>40</entry><entry>Ad 100</entry><entry>40,2</entry><entry>Ad 100</entry><entry>40</entry><entry>Ad 100</entry></row><row><entry>Powdered isomalt</entry><entry>9,5</entry><entry>9,5</entry><entry>9,5</entry><entry>9,5</entry><entry>9,5</entry><entry>9,5</entry></row><row><entry>Xylitol</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry><entry>2</entry></row><row><entry>Mannit D</entry><entry>3</entry><entry>3</entry><entry>3</entry><entry>3</entry><entry>3</entry><entry>3</entry></row><row><entry>Aspartame</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>Acesulfame K</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>EmulgumTM (soy lecithins with a high content of phospholipids)</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry></row><row><entry>Sorbitol (70% in water)</entry><entry>13</entry><entry>13</entry><entry>13</entry><entry>13</entry><entry>13</entry><entry>13</entry></row><row><entry>1,2-propylene glycol</entry><entry>-</entry><entry>1</entry><entry>-</entry><entry>1</entry><entry>-</entry><entry>1</entry></row><row><entry>Glycerin</entry><entry>1</entry><entry>-</entry><entry>1</entry><entry>-</entry><entry>1</entry><entry>-</entry></row><row><entry>PLM pellitor solution (containing 10% pellitor)</entry><entry>-</entry><entry>0,035</entry><entry>-</entry><entry>0,035</entry><entry>-</entry><entry>0,035</entry></row><row><entry>Aroma eucalyptus type peppermint (example S-5a)</entry><entry>1</entry><entry>1</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma eucalyptus type peppermint (example S-5d)</entry><entry /><entry /><entry>0,8</entry><entry>0,8</entry><entry /><entry /></row><row><entry>Aroma eucalyptus type peppermint (example S-5f)</entry><entry /><entry /><entry /><entry /><entry>1</entry><entry>1</entry></row></tbody></tgroup></table></tables>

Example S-21

Chewing gum (with sugar and sugar-free)

0486Unless otherwise noted, all data in% by weight.<tables id="tabl0050" num="0050"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="58mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Gum base</entry><entry>21</entry><entry>30</entry><entry>21</entry><entry>30</entry><entry>21</entry><entry>30</entry></row><row><entry>Glycerin</entry><entry>0,5</entry><entry>1</entry><entry>0,5</entry><entry>1</entry><entry>0,5</entry><entry>1</entry></row><row><entry>Glucose syrup</entry><entry>16,5</entry><entry>-</entry><entry>16,5</entry><entry>-</entry><entry>16,5</entry><entry>-</entry></row><row><entry>powdered sugar</entry><entry>Ad 100</entry><entry>-</entry><entry>Ad 100</entry><entry>-</entry><entry>Ad 100</entry><entry>-</entry></row><row><entry>Sorbitol (in powder form)</entry><entry>-</entry><entry>Ad 100</entry><entry>-</entry><entry>Ad 100</entry><entry>-</entry><entry>Ad 100</entry></row><row><entry>Palatinite</entry><entry>-</entry><entry>9,5</entry><entry>-</entry><entry>9,5</entry><entry>-</entry><entry>9,5</entry></row><row><entry>Xylitol</entry><entry>-</entry><entry>2</entry><entry>-</entry><entry>2</entry><entry>-</entry><entry>2</entry></row><row><entry>Mannitol</entry><entry>-</entry><entry>3</entry><entry>-</entry><entry>3</entry><entry>-</entry><entry>3</entry></row><row><entry>Aspartame</entry><entry>-</entry><entry>0,1</entry><entry>-</entry><entry>0,1</entry><entry>-</entry><entry>0,1</entry></row><row><entry>Acesulfame K</entry><entry>-</entry><entry>0,1</entry><entry>-</entry><entry>0,1</entry><entry>-</entry><entry>0,1</entry></row><row><entry>EmulgumTM (emulsifier)</entry><entry>-</entry><entry>0,3</entry><entry>-</entry><entry>0,3</entry><entry>-</entry><entry>0,3</entry></row><row><entry>Sorbitol 70%, in water</entry><entry>-</entry><entry>14</entry><entry>-</entry><entry>14</entry><entry>-</entry><entry>14</entry></row><row><entry>Flavor type mint (example S-6a)</entry><entry>1</entry><entry>1,4</entry><entry /><entry /><entry /><entry /></row><row><entry>Flavor type mint (example S-6f)</entry><entry /><entry /><entry>0,8</entry><entry>1,2</entry><entry /><entry /></row><row><entry>Flavor type mint (example S-6h)</entry><entry /><entry /><entry /><entry /><entry>1</entry><entry>1,4</entry></row></tbody></tgroup></table></tables>

Example S-22

Sugar-free chewing gum

0487The chewing gum base K1 consisted of 2.0% butyl rubber (isobutene-isoprene copolymer, MW = 400000, 6.0% polyisobutene (MW = 43.800), 43.5% polyvinyl acetate (MW = 12.000), 31.5% polyvinyl acetate ( MW = 47,000), 6.75% triacetin and 10.25% calcium carbonate The chewing gum base K1 and the chewing gums can be prepared analogously to US Pat. No. 5,601,858.

0488Unless otherwise noted, all data in% by weight.<tables id="tabl0051" num="0051"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="66mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Chewing gum base K1</entry><entry>26</entry><entry>27</entry><entry>26</entry><entry>26</entry><entry>27</entry><entry>26</entry></row><row><entry>Triacetin</entry><entry>0,25</entry><entry>0,25</entry><entry>0,25</entry><entry>0,25</entry><entry>0,25</entry><entry>0,25</entry></row><row><entry>Lecithin</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Sorbitol, crystalline</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry></row><row><entry>Mannitol</entry><entry>15,3</entry><entry>15,2</entry><entry>15,1</entry><entry>15,3</entry><entry>15,2</entry><entry>15,1</entry></row><row><entry>Glycerin</entry><entry>12,1</entry><entry>12</entry><entry>11,8</entry><entry>12,1</entry><entry>12</entry><entry>11,8</entry></row><row><entry>Saccharin-Na</entry><entry>0,17</entry><entry>-</entry><entry>0,1</entry><entry>0,17</entry><entry>-</entry><entry>0,1</entry></row><row><entry>Encapsulated aspartame</entry><entry>1,08</entry><entry>1,18</entry><entry>1,08</entry><entry>1,08</entry><entry>1,18</entry><entry>1,08</entry></row><row><entry>Amorphous silica</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry></row><row><entry>Cottonseed oil</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry><entry>0,5</entry></row><row><entry>Polyoxyethylene sorbitan monolaurate (E-432)</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry><entry>1</entry></row><row><entry>Encapsulated I-Carvon (loading: 30%)</entry><entry>-</entry><entry>0,2</entry><entry>-</entry><entry>-</entry><entry>0,2</entry><entry>-</entry></row><row><entry>I-menthyl-I-lactate</entry><entry>-</entry><entry>-</entry><entry>0,2</entry><entry>-</entry><entry>-</entry><entry>0,2</entry></row><row><entry>Flavor type mint (example S-6c)</entry><entry>1</entry><entry>-</entry><entry>1,7</entry><entry /><entry /><entry /></row><row><entry>Flavor type mint (example S-6d)</entry><entry /><entry /><entry /><entry>0,8</entry><entry>-</entry><entry>1,4</entry></row><row><entry>Peppermint flavor (example S-5b)</entry><entry>0,5</entry><entry>1,4</entry><entry>-</entry><entry /><entry /><entry /></row><row><entry>Peppermint flavor (example S-5e)</entry><entry /><entry /><entry /><entry>0,5</entry><entry>1,4</entry><entry>-</entry></row></tbody></tgroup></table></tables>

Example S-23

Sugar-free chewing gum

0489Unless otherwise noted, all data in% by weight.

0490The chewing gum base K2 consisted of 28.5% terpene resin, 33.9% polyvinyl acetate (MW = 14,000), 16.25% hydrogenated vegetable oil, 5.5% mono- and diglycerides, 0.5% polyisobutene (MW 75,000), 2. 0% butyl rubber (isobutene-isoprene copolymer), 4.6% amorphous silicon dioxide (water content approx.2.5%), 0.05% antioxidant tert-butylated hydroxytoluene (BHT), 0.2% lecitihin, and 8, 5% calcium carbonate. The manufacture of the chewing gum base K2 and the chewing gums can be carried out analogously to<patcit id="pcit0076" dnum="US6986907B"><text>US 6,986,907</text></patcit> respectively.<tables id="tabl0052" num="0052"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="76mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Chewing gum base K2</entry><entry>25,3</entry><entry>27,3</entry><entry>26,3</entry><entry>25,3</entry><entry>27,3</entry><entry>26,3</entry></row><row><entry>Sorbitol</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry></row><row><entry>Glycerin</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry></row><row><entry>Lecithin</entry><entry>7</entry><entry>7</entry><entry>7</entry><entry>7</entry><entry>7</entry><entry>7</entry></row><row><entry>Aspartame</entry><entry>0,14</entry><entry>0,14</entry><entry>0,14</entry><entry>0,14</entry><entry>0,14</entry><entry>0,14</entry></row><row><entry>Encapsulated aspartame</entry><entry>0,68</entry><entry>0,68</entry><entry>0,68</entry><entry>0,68</entry><entry>0,68</entry><entry>0,68</entry></row><row><entry>Menthol, spray dried (loading: 25%)</entry><entry>0,5</entry><entry>-</entry><entry>0,5</entry><entry>0,5</entry><entry>-</entry><entry>0,5</entry></row><row><entry>Cherry flavor, spray dried (contains benzaldehyde)</entry><entry>-</entry><entry>1</entry><entry>-</entry><entry>-</entry><entry>1</entry><entry>-</entry></row><row><entry>Peppermint flavor (Example S-5b), spray dried, 30% flavor</entry><entry>1,5</entry><entry>1,7</entry><entry>-</entry><entry /><entry /><entry /></row><row><entry>Peppermint flavor (Example S-5c), spray-dried, 30% flavor</entry><entry /><entry /><entry /><entry>1,5</entry><entry>1,7</entry><entry>-</entry></row><row><entry>Aroma type spicy-aromatic (example S-7c)</entry><entry>1</entry><entry>-</entry><entry>1,5</entry><entry /><entry /><entry /></row><row><entry>Aroma type spicy-aromatic (example S-7h)</entry><entry /><entry /><entry /><entry>1</entry><entry>-</entry><entry>1,5</entry></row></tbody></tgroup></table></tables>

0491The recipe chewing gum (<u>1</u>) and (<u>2</u>) were created as strips that match the recipe (<u>3</u>) made as a compact in pillow form and then coated with xylitol.

Example S-24

0492Production of aromas with a cooling effect of the "ice candy" taste type using the cooling substances according to the invention.

The following were mixed:

(All data, unless otherwise noted, in% by weight.)

0493<tables id="tabl0053" num="0053"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="81mm" /><colspec colnum="2" colname="col2" colwidth="10mm" /><colspec colnum="3" colname="col3" colwidth="10mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="10mm" /><colspec colnum="9" colname="col9" colwidth="10mm" /><thead><row><entry>component</entry><entry>a</entry><entry>b</entry><entry>c</entry><entry>d</entry><entry>e</entry><entry>f</entry><entry>G</entry><entry>H</entry></row></thead><tbody><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Isoamyl acetate</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry><entry valign="bottom">2</entry></row><row><entry valign="bottom">Ethyl butyrate</entry><entry valign="bottom">0,5</entry><entry valign="bottom">-</entry><entry valign="bottom">0,5</entry><entry valign="bottom">-</entry><entry valign="bottom">0,5</entry><entry valign="bottom">-</entry><entry valign="bottom">0,5</entry><entry valign="bottom">-</entry></row><row><entry valign="bottom">Butyl butyrate</entry><entry valign="bottom">-</entry><entry valign="bottom">0,5</entry><entry valign="bottom">-</entry><entry valign="bottom">0,5</entry><entry valign="bottom">-</entry><entry valign="bottom">0,5</entry><entry valign="bottom">-</entry><entry valign="bottom">0,5</entry></row><row><entry valign="bottom">Ethyl vanillin</entry><entry valign="bottom">2</entry><entry valign="bottom">-</entry><entry valign="bottom">2</entry><entry valign="bottom">-</entry><entry valign="bottom">2</entry><entry valign="bottom">-</entry><entry valign="bottom">2</entry><entry valign="bottom">-</entry></row><row><entry valign="bottom">Vanillin</entry><entry valign="bottom">-</entry><entry valign="bottom">1</entry><entry valign="bottom">-</entry><entry valign="bottom">1</entry><entry valign="bottom">-</entry><entry valign="bottom">1</entry><entry valign="bottom">-</entry><entry valign="bottom">1</entry></row><row><entry valign="bottom">FrambinonTM [4- (4-hydroxyphenyl) -2-butanone]</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry></row><row><entry valign="bottom">l-menthol</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom">5</entry></row><row><entry valign="bottom">Peppermint oil, type piperita</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry></row><row><entry valign="bottom">Triacetin</entry><entry valign="bottom">-</entry><entry valign="bottom">84</entry><entry valign="bottom">-</entry><entry valign="bottom">84,5</entry><entry valign="bottom">-</entry><entry valign="bottom">84,5</entry><entry valign="bottom">-</entry><entry valign="bottom">84</entry></row><row><entry valign="bottom">1,2-propylene glycol</entry><entry valign="bottom">83</entry><entry valign="bottom">-</entry><entry valign="bottom">83,5</entry><entry valign="bottom">-</entry><entry valign="bottom">83,5</entry><entry valign="bottom">-</entry><entry valign="bottom">83</entry><entry valign="bottom">-</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry></row><row><entry valign="bottom">sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry></row></tbody></tgroup></table></tables>

0494The flavors were incorporated into various candy masses at concentrations of 0.15 to 0.2% by weight. The sensory evaluation by a trained panel of experts showed that the aroma led to a strong, quick-setting, very long-lasting freshness effect that persisted for well over 30 minutes even after the candy was consumed.

Example S-25

Hardboiled candy, sugar-free

0495Unless otherwise noted, all data in% by weight.<tables id="tabl0054" num="0054"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="73mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>water</entry><entry>2,24</entry><entry>2,24</entry><entry>2,24</entry><entry>2,24</entry><entry>2,24</entry><entry>2,24</entry></row><row><entry>Isomalt</entry><entry>94,98</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>94,98</entry><entry>Ad 100</entry><entry>Ad 100</entry></row><row><entry>Xylitol</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry><entry>2,4</entry></row><row><entry>Sucralose</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry></row><row><entry>Acesulfame K</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry></row><row><entry>Citric acid</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry></row><row><entry>PLM pellitor solution (containing 10% pellitor)</entry><entry>-</entry><entry>0,0075</entry><entry>0,01</entry><entry>-</entry><entry>0,0075</entry><entry>0,01</entry></row><row><entry>Aroma eucalyptus menthol type (example S-1c)</entry><entry>0,25</entry><entry>0,2</entry><entry /><entry /><entry /><entry /></row><row><entry>Aroma eucalyptus menthol type (example S-1d)</entry><entry /><entry /><entry /><entry>0,25</entry><entry>0,2</entry><entry /></row><row><entry>Flavor type ice cream (example S-24a)</entry><entry /><entry /><entry>0,25</entry><entry /><entry /><entry /></row><row><entry>Flavor type ice cream (example S-24e)</entry><entry /><entry /><entry /><entry /><entry /><entry>0,2</entry></row></tbody></tgroup></table></tables>

Example S-26

Hardboiled candy

0496Unless otherwise noted, all data in% by weight.<tables id="tabl0055" num="0055"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="59mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><colspec colnum="7" colname="col7" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>water</entry><entry>2,75</entry><entry>2,5</entry><entry>2,5</entry><entry>2,75</entry><entry>2,5</entry><entry>2,5</entry></row><row><entry>sugar</entry><entry>60,1</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>60,1</entry><entry>Ad 100</entry><entry>Ad 100</entry></row><row><entry>Glucose syrup</entry><entry>36,9</entry><entry>36</entry><entry>36</entry><entry>36,9</entry><entry>36</entry><entry>36</entry></row><row><entry>Maltose</entry><entry>-</entry><entry>2</entry><entry>2</entry><entry>-</entry><entry>2</entry><entry>2</entry></row><row><entry>Palm kernel oil</entry><entry>-</entry><entry>0,8</entry><entry>0,8</entry><entry>-</entry><entry>0,8</entry><entry>0,8</entry></row><row><entry>Citric acid</entry><entry>-</entry><entry>0,25</entry><entry>0,25</entry><entry>-</entry><entry>0,25</entry><entry>0,25</entry></row><row><entry>Ginseng extract</entry><entry>-</entry><entry>0,4</entry><entry>0,4</entry><entry>-</entry><entry>0,4</entry><entry>0,4</entry></row><row><entry>Blue dye</entry><entry>-</entry><entry>0,01</entry><entry>0,01</entry><entry>-</entry><entry>0,01</entry><entry>0,01</entry></row><row><entry>Aroma mint type (example S-2a)</entry><entry>0,25</entry><entry>0,35</entry><entry>-</entry><entry /><entry /><entry /></row><row><entry>Aroma mint type (example S-2d)</entry><entry /><entry /><entry /><entry>0,25</entry><entry>0,35</entry><entry>-</entry></row><row><entry>Flavor type ice cream (example S-24b)</entry><entry /><entry /><entry>0,175</entry><entry /><entry /><entry /></row><row><entry>Flavor type ice cream (example S-24d)</entry><entry /><entry /><entry /><entry /><entry /><entry>0,175</entry></row></tbody></tgroup></table></tables>

Example S-27

Instant beverage powder

0497Unless otherwise noted, all data in% by weight.<tables id="tabl0056" num="0056"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="71mm" /><colspec colnum="2" colname="col2" colwidth="16mm" /><colspec colnum="3" colname="col3" colwidth="16mm" /><colspec colnum="4" colname="col4" colwidth="16mm" /><colspec colnum="5" colname="col5" colwidth="16mm" /><colspec colnum="6" colname="col6" colwidth="16mm" /><colspec colnum="7" colname="col7" colwidth="16mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Sugar (sucrose)</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry><entry>Ad 100</entry></row><row><entry>Citric acid</entry><entry>11,58</entry><entry>11,58</entry><entry>11,58</entry><entry>11,58</entry><entry>11,58</entry><entry>11,58</entry></row><row><entry>Trisodium citrate</entry><entry>0,7</entry><entry>0,7</entry><entry>0,7</entry><entry>0,7</entry><entry>0,7</entry><entry>0,7</entry></row><row><entry>Tricalcium phosphate</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry><entry>0,6</entry></row><row><entry>vitamin C</entry><entry>0,66</entry><entry>0,66</entry><entry>0,66</entry><entry>0,66</entry><entry>0,66</entry><entry>0,66</entry></row><row><entry>Grindsted® JU 543 Stabilizer System (Danisco)</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry></row><row><entry>Saccharin</entry><entry>0,561</entry><entry>0,561</entry><entry>0,561</entry><entry>0,561</entry><entry>0,561</entry><entry>0,561</entry></row><row><entry>Lemon aroma, spray dried</entry><entry>1,75</entry><entry>-</entry><entry>1,75</entry><entry>-</entry><entry>1,75</entry><entry>-</entry></row><row><entry>Orange aroma, spray dried</entry><entry /><entry>1,85</entry><entry /><entry>1,85</entry><entry /><entry>1,85</entry></row><row><entry>Aroma eucalyptus menthol type (example S-1a), spray dried on maltodextrin (DE 15-19) and gum arabic, aroma load 40%</entry><entry>1,75</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Aroma eucalyptus menthol type (example S-1c), spray-dried on maltodextrin (DE 15-19) and gum arabic, aroma load 40%</entry><entry /><entry /><entry>1,75</entry><entry /><entry /><entry /></row><row><entry>Aroma eucalyptus menthol type (example S-1h), spray dried on maltodextrin (DE 15-19) and gum arabic, aroma load 40%</entry><entry /><entry /><entry /><entry /><entry>1,75</entry><entry /></row><row><entry valign="bottom">Aroma type spicy-aromatic (menthol cinnamon) (Example S-3b); spray dried on maltodextrin (DE 15-19) and gum arabic, aroma load 40%</entry><entry valign="bottom" /><entry valign="bottom">1,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Aroma type spicy-aromatic (menthol cinnamon) (example S-3d); spray dried on maltodextrin (DE 15-19) and gum arabic, aroma load 40%</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1,2</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Aroma type spicy-aromatic (menthol cinnamon) (Example S-3e); spray dried on maltodextrin (DE 15-19) and gum arabic, aroma load 40%</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1,2</entry></row></tbody></tgroup></table></tables>

049845 g of this instant beverage powder were each dissolved in 1000 mL with stirring. The drinks obtained had a refreshing, cooling taste of citrus, cinnamon and mint.

Example S-28

Neck candies with liquid-viscous core filling (center-filled hard candy)

0499Unless otherwise noted, all data in% by weight.<tables id="tabl0057" num="0057"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="81mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top">component</entry><entry valign="top"><u>1</u></entry><entry valign="top"><u>2</u></entry><entry valign="top"><u>3</u></entry><entry valign="top"><u>4</u></entry><entry valign="top"><u>5</u></entry><entry valign="top"><u>6</u></entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row></tbody></tgroup><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="81mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top"><u><b>Mix A (shell)</b> (80% of the sweets)</u></entry><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /></row></thead><tbody><row><entry>Sugar (sucrose)</entry><entry>58,1</entry><entry>58,1</entry><entry>58,1</entry><entry>49,36</entry><entry>49,36</entry><entry>49,36</entry></row><row><entry>Glucose syrup (solids content 80%)</entry><entry>41,51</entry><entry>41,51</entry><entry>41,51</entry><entry>49,36</entry><entry>49,36</entry><entry>49,36</entry></row><row><entry>Aroma type spicy-aromatic (menthol cinnamon) (example S-3a)</entry><entry>0,17</entry><entry>0,17</entry><entry>0,17</entry><entry>0,25</entry><entry>0,25</entry><entry>0,25</entry></row><row><entry>Aroma type spicy-aromatic (menthol cinnamon) (example S-3c)</entry><entry>0,17</entry><entry>0,17</entry><entry>0,17</entry><entry>0,25</entry><entry>0,25</entry><entry>0,25</entry></row><row><entry>Aroma type spicy-aromatic (menthol cinnamon) (example S-3f)</entry><entry>0,17</entry><entry>0,17</entry><entry>0,17</entry><entry>0,25</entry><entry>0,25</entry><entry>0,25</entry></row><row><entry>Tr.-Pellitorin 10% in propylene glycol / peppermint oil (1: 1)</entry><entry>0,02</entry><entry>0,02</entry><entry>0,02</entry><entry>0,03</entry><entry>0,03</entry><entry>0,03</entry></row><row><entry>l-menthol</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>-</entry><entry>-</entry><entry>-</entry></row><row><entry>Lemon oil</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>Citric acid</entry><entry>-</entry><entry>-</entry><entry>-</entry><entry>0,9</entry><entry>0,9</entry><entry>0,9</entry></row><row><entry>Total:</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry><entry>100</entry></row></tbody></tgroup><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="81mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top"><b><u>Mix B (core)</u></b> (20% of the sweets)</entry><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /><entry valign="top" /></row></thead><tbody><row><entry>High fructose corn syrup (solid sugar content 85%, almost 15% water)</entry><entry>84,35 5</entry><entry>84,355</entry><entry>84,355</entry><entry>84,31</entry><entry>84,31</entry><entry>84,31</entry></row><row><entry>Glycerin</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry><entry>15</entry></row><row><entry>Lecithin</entry><entry>0,02</entry><entry>0,02</entry><entry>0,02</entry><entry>0,02</entry><entry>0,02</entry><entry>0,02</entry></row><row><entry>Cinnamon oil</entry><entry>-</entry><entry>-</entry><entry>-</entry><entry>0,27</entry><entry>0,27</entry><entry>0,27</entry></row><row><entry>Flavor type spearmint (example S-2b)</entry><entry>0,28</entry><entry>0,28</entry><entry>0,28</entry><entry>-</entry><entry>-</entry><entry>-</entry></row><row><entry>Flavor type spearmint (example S-2d)</entry><entry>0,28</entry><entry>0,28</entry><entry>0,28</entry><entry>-</entry><entry>-</entry><entry>-</entry></row><row><entry>Flavor type spearmint (example S-2g)</entry><entry>0,28</entry><entry>0,28</entry><entry>0,28</entry><entry>-</entry><entry>-</entry><entry>-</entry></row><row><entry>Capsaicin</entry><entry>0,025</entry><entry>0,025</entry><entry>0,025</entry><entry>-</entry><entry>-</entry><entry>-</entry></row><row><entry>Piperine</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry><entry>0,05</entry></row><row><entry>Vanillyl alcohol n-butyl ether</entry><entry>-</entry><entry>-</entry><entry>-</entry><entry>0,1</entry><entry>0,1</entry><entry>0,1</entry></row><row><entry>Red dye, as a 2.5% aqueous solution</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Vanillin</entry><entry>0,07</entry><entry>0,07</entry><entry>0,07</entry><entry>-</entry><entry>-</entry><entry>-</entry></row></tbody></tgroup></table></tables>

0500Based on the in <patcit id="pcit0077" dnum="US6432441B"><text>US 6,432,441</text></patcit> (there example 1) as well as in <patcit id="pcit0078" dnum="US5458894A"><text>US 5,458,894</text></patcit> respectively. <patcit id="pcit0079" dnum="US5002791A"><text>US 5,002,791</text></patcit> described processes, candies with a liquid-viscous core were produced. Both mixtures A and B were processed separately to form bases for shell (mixture A) or core (mixture B). The filled throat candies obtained by co-extrusion were effective against cough, sore throat and hoarseness when consumed in affected persons.

Example S-29

Gelatine capsules suitable for direct consumption

0501Unless otherwise noted, all data in% by weight.<tables id="tabl0058" num="0058"><table frame="all"><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="93mm" /><colspec colnum="2" colname="col2" colwidth="16mm" /><colspec colnum="3" colname="col3" colwidth="16mm" /><thead><row><entry valign="top">Components</entry><entry valign="top"><u>1</u></entry><entry valign="top"><u>2</u></entry></row><row><entry valign="top"><b>Gelatin shell:</b></entry><entry valign="top" /><entry valign="top" /></row></thead><tbody><row><entry>Glycerin</entry><entry>2,014</entry><entry>2,014</entry></row><row><entry>Gelatin 240 Bloom</entry><entry>7,91</entry><entry>7,91</entry></row><row><entry>Sucralose</entry><entry>0,070</entry><entry>0,070</entry></row><row><entry>Allura Red (red dye)</entry><entry>0,006</entry><entry>0,006</entry></row><row><entry>Brilliant Blue (blue dye)</entry><entry>0,005</entry><entry>0,005</entry></row></tbody></tgroup><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="93mm" /><colspec colnum="2" colname="col2" colwidth="16mm" /><colspec colnum="3" colname="col3" colwidth="16mm" /><thead><row><entry valign="top"><b>Core composition:</b></entry><entry valign="top" /><entry valign="top" /></row></thead><tbody><row><entry>Aroma eucalyptus menthol type (example S-1a)</entry><entry>15</entry><entry /></row><row><entry>Aroma eucalyptus menthol type (example S-1b)</entry><entry /><entry>15</entry></row><row><entry>Vegetable oil triglycerides (coconut oil fraction)</entry><entry>Ad 100</entry><entry>Ad 100</entry></row></tbody></tgroup></table></tables>

0502The gelatin capsules suitable for direct consumption were prepared in accordance with <patcit id="pcit0080" dnum="WO2004050069A"><text>WO 2004/050069</text></patcit> manufactured and had a diameter of 5 mm; the weight ratio of core material to shell material was 90:10. The capsules each opened in the mouth within less than 10 seconds and completely dissolved in less than 50 seconds.

Example S-30

0503Production of a chewing candy with a cooling raspberry taste using the cooling substances according to the invention.

0504Unless otherwise noted, all data in% by weight.<tables id="tabl0059" num="0059"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="93mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><thead><row><entry valign="top">Components</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>water</entry><entry>7,8</entry><entry>7,8</entry><entry>7,8</entry><entry>7,8</entry><entry>7,8</entry><entry>7,8</entry></row><row><entry>Sugar refined sugar C4</entry><entry>42,1</entry><entry>42,1</entry><entry>42,1</entry><entry>42,1</entry><entry>42,1</entry><entry>42,1</entry></row><row><entry>Glucose syrup dextrose 40</entry><entry>37,3</entry><entry>37,3</entry><entry>37,3</entry><entry>37,3</entry><entry>37,3</entry><entry>37,3</entry></row><row><entry>hardened vegetable fat melting point 32-36 ° C</entry><entry>6,6</entry><entry>6,6</entry><entry>6,6</entry><entry>6,6</entry><entry>6,6</entry><entry>6,6</entry></row><row><entry>Lecithin emulsifier (soy lecithin)</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry><entry>0,3</entry></row><row><entry>Gelatin (pork gelatin)</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry><entry>0,8</entry></row><row><entry>Fondant type - S30</entry><entry>4,8</entry><entry>4,8</entry><entry>4,8</entry><entry>4,8</entry><entry>4,8</entry><entry>4,8</entry></row><row><entry>Raspberry flavor</entry><entry>0,22</entry><entry>0,22</entry><entry>0,22</entry><entry>0,22</entry><entry>0,22</entry><entry>0,22</entry></row><row><entry>Menthyl lactate</entry><entry>0,06</entry><entry>0,06</entry><entry>0,06</entry><entry>0,06</entry><entry>0,06</entry><entry>0,06</entry></row><row><entry>3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry>0,02</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry /><entry>0,03</entry><entry /><entry /><entry /><entry /></row><row><entry>Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry /><entry /><entry>0,015</entry><entry /><entry /><entry /></row><row><entry valign="bottom">(5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) isopropylamine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,02</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,005</entry><entry valign="bottom" /></row><row><entry valign="bottom">2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,01</entry></row></tbody></tgroup></table></tables>

Manufacturing instructions:

0505<ol id="ol0007" compact="compact"><li>a) Allow gelatin to swell with water (1.8 times the amount of gelatin) at 70 ° C for 2 hours;</li><li>b) Boil sugar, syrup, water, fat and lecithin to 123 ° C;</li><li>c) Slowly mix the gelatin solution with the cooking mixture;</li><li>d) Mix the raspberry aroma, menthyl lactate and the cooling substances according to the invention and optionally stir in the color;</li><li>e) temper the resulting mass on a cooling table to approx. 70 ° C, then add fondant and aerate on a drawing machine for approx. 3 minutes;</li><li>f) Then cut and pack the chewy candy.</li></ol>

0506When chewing candy is consumed, a fresh, cooling raspberry taste is perceived during chewing.

Example S-31

Production of an extrudate for the preparation of beverage mixes with cooling effect

0507Unless otherwise noted, all data in% by weight.<tables id="tabl0060" num="0060"><table frame="all"><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="131mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><thead><row><entry valign="top">component</entry><entry valign="top" /><entry valign="top" /><entry valign="top" /></row></thead><tbody><row><entry>Spray dried glucose syrup (DE value: 31-34) [Glucidex IT33W (Roquette)]</entry><entry>62,0</entry><entry>62,0</entry><entry>62,0</entry></row><row><entry>Maltodextrin (DE value: 17-20), company Cerestar</entry><entry>28,4</entry><entry>28,4</entry><entry>28,4</entry></row><row><entry>Emulsifier Monomuls, emulsifier based on hardened palm oil; Melting point: 64 ° C, (Grünau company)</entry><entry>1,8</entry><entry>1,8</entry><entry>1,8</entry></row><row><entry>Dextrose monohydrate (DE value: 99.5), from Cerestar</entry><entry>1,8</entry><entry>1,8</entry><entry>1,8</entry></row><row><entry>water</entry><entry>2,0</entry><entry>2,0</entry><entry>2,0</entry></row><row><entry>Orange-vanilla flavor</entry><entry>3,2</entry><entry>3,2</entry><entry>3,2</entry></row><row><entry>Aroma eucalyptus menthol type (example S-1a)</entry><entry>0,8</entry><entry /><entry /></row><row><entry>Aroma eucalyptus menthol type (example S-1b)</entry><entry /><entry>0,8</entry><entry /></row><row><entry>Aroma eucalyptus menthol type (example S-1f)</entry><entry /><entry /><entry>0,8</entry></row></tbody></tgroup></table></tables>

Manufacturing note (see also WO 03/092412):

0508All components were mixed and fed into a twin-screw extruder by single-point metering. The extrusion temperatures were between 100 and 120 ° C, the specific energy input was 0.2 kWh / kg. The strands emerging from the die plate of the extruder provided with 1 mm bores were cut immediately after emerging from the nozzles by rotating knives onto particles with a diameter of approx. 1 mm.

Example S-32

Production of fluidized bed granules for the preparation of beverage mixes with a cooling effect

0509In a pelletizer of the in <patcit id="pcit0081" dnum="EP163836A"><text>EP 163 836</text></patcit> shown type (with the following characteristics: diameter inflow base: 225 mm, spray nozzle: two-substance nozzle; sifting discharge: zigzag sifter; filter: internal bag filter), a solution consisting of 44 wt .-% water, 8 wt.% lemon aroma, 3 wt .-% aroma eucalyptus-menthol type (see example S-1a to S-1h), 13% by weight gum arabic and 32% by weight hydrolyzed starch (maltodextrin DE 15-19) and a little green pigment granulated. The solution is sprayed into the fluidized bed granulator at a temperature of 32 ° C. Nitrogen is blown in at a rate of 140 kg / h to fluidize the bed contents. The inlet temperature of the fluidizing gas is 140 ° C. The temperature of the exhaust gas is 76 ° C. Nitrogen is also supplied as a visible gas in an amount of 15 kg / h at a temperature of 50 ° C. The content of the fluidized bed is approx. 500 g. The granulation capacity is approx. 2.5 kg per hour. A free-flowing granulate with an average particle diameter of 360 micrometers is obtained. The granules are round and have a smooth surface. Due to the constant pressure loss of the filter and the constant bed content, stationary conditions with regard to the granulation process can be assumed.

Example S-33

0510Production of tea bags with rooibos or black tea and extrudates from Example S-31 or granules from Example S-32 for the preparation of tea drinks with a cooling effect.

0511In each case 800 g of red bush tea (rooibos tea) were mixed once with 33 g of the extrudates from example S-31 and once with 30 g granules from application example 32, portioned and then filled into tea bags.

0512In each case 800 g of black tea (leaf grade fannings) were mixed once with 33 g of the extrudates from Example S-31 and once with 30 g granules from Example S-32, portioned and then filled into tea bags.

Example S-34

0513Production of a sugar-containing or reduced-sugar ice cream with a long-lasting cooling effect using the cooling substances according to the invention

0514Unless otherwise noted, all data in% by weight.<tables id="tabl0061" num="0061"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="86mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Skimmed milk</entry><entry>57,15</entry><entry>60,95</entry><entry>57,15</entry><entry>60,95</entry><entry>57,15</entry><entry>60,95</entry></row><row><entry>Vegetable fat, melting range 35 - 40 ° C</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry><entry>20</entry></row><row><entry>Sugar (sucrose)</entry><entry>12</entry><entry>8</entry><entry>12</entry><entry>8</entry><entry>12</entry><entry>8</entry></row><row><entry>Skimmed milk powder</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry></row><row><entry>Glucose syrup 72% dry matter</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry><entry>5</entry></row><row><entry>Emulsifier SE 30 (Grindstedt Products, Denmark)</entry><entry>0,65</entry><entry>0,65</entry><entry>0,65</entry><entry>0,65</entry><entry>0,65</entry><entry>0,65</entry></row><row><entry>Vanilla flavor containing 1% vanillin and 2.5% 3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Vanilla aroma containing 1% vanillin and 1% 2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan-] -1-one</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Vanilla flavor containing 1% vanillin and 2% isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Hesperitin, 2.5% in 1,2-propylene glycol</entry><entry>0</entry><entry>0,2</entry><entry>0</entry><entry>0,2</entry><entry>0</entry><entry>0,2</entry></row></tbody></tgroup></table></tables>

0515Skim milk and glucose syrup were heated to 55 ° and sugar, skimmed milk powder and emulsifier were added. The vegetable fat was preheated and the entire mass heated to 58 ° C. After the aroma had been added, the mixture was homogenized using a high-pressure homogenizer (180/50 bar). The mass obtained was tempered at 78 ° C. for 1 min, then cooled to 2-4 ° C. and incubated at this temperature for 10 h for ripening. The matured mass was then filled and stored frozen at -18 ° C.

Example S-35

0516Production of sugar-containing and reduced-sugar soft drinks of various flavors and a long-lasting refreshing feeling of cooling using the cooling substances according to the invention.<tables id="tabl0062" num="0062"><table frame="all"><tgroup cols="10"><colspec colnum="1" colname="col1" colwidth="48mm" /><colspec colnum="2" colname="col2" colwidth="26mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><colspec colnum="10" colname="col10" colwidth="12mm" /><thead><row><entry>component</entry><entry>salary</entry><entry namest="col3" nameend="col10" align="left">preparation</entry></row><row><entry /><entry>Weight percentage</entry><entry><u>1</u></entry><entry><u>2</u></entry><entry><u>3</u></entry><entry><u>4</u></entry><entry><u>5</u></entry><entry><u>6</u></entry><entry><u>7</u></entry><entry><u>8</u></entry></row></thead><tbody><row><entry valign="bottom">Sucrose</entry><entry valign="bottom">%</entry><entry valign="bottom">10,5</entry><entry valign="bottom">8</entry><entry valign="bottom">8</entry><entry valign="bottom">8</entry><entry valign="bottom">8</entry><entry valign="bottom">8</entry><entry valign="bottom">8</entry><entry valign="bottom">8</entry></row><row><entry valign="bottom">Citric acid</entry><entry valign="bottom">%</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry><entry valign="bottom">0,2</entry></row><row><entry valign="bottom">Hesperetin 1% in 1,2-propylene glycol</entry><entry valign="bottom">%</entry><entry valign="bottom" /><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry></row><row><entry valign="bottom">Phloretin 1% in 1,2-propylene glycol</entry><entry valign="bottom">%</entry><entry valign="bottom" /><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,05</entry><entry valign="bottom">0,1</entry><entry valign="bottom">0,1</entry><entry valign="bottom">0,1</entry></row><row><entry valign="bottom">Ethylhydroxymethylfuranone</entry><entry valign="bottom">ppb</entry><entry valign="bottom">0,01</entry><entry valign="bottom">0,01</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Vanillin</entry><entry valign="bottom">ppb</entry><entry valign="bottom">15</entry><entry valign="bottom">15</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Diethyl malonate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">70</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Phenylethyl acetate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">1</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">2-methylbutanal</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Isovaleraldehyde</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Furfury acetate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,3</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Massoilactone</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom" /><entry valign="bottom">5</entry></row><row><entry valign="bottom">γ-octalactone</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">5</entry><entry valign="bottom">5</entry><entry valign="bottom" /><entry valign="bottom">5</entry></row><row><entry valign="bottom">Ethyl butyrate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /><entry valign="bottom">0,5</entry></row><row><entry valign="bottom">Maltol</entry><entry valign="bottom">ppb</entry><entry valign="bottom">350</entry><entry valign="bottom">350</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">350</entry><entry valign="bottom" /><entry valign="bottom">350</entry></row><row><entry valign="bottom">2,5-dimethyl-4-hydroxy-2H-furan-3-one</entry><entry valign="bottom">ppb</entry><entry valign="bottom">3</entry><entry valign="bottom">3</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">3</entry><entry valign="bottom" /><entry valign="bottom">3</entry></row><row><entry valign="bottom">Ethyl isobutyrate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom" /><entry valign="bottom">0,1</entry></row><row><entry valign="bottom">Ethyl 2-methylbutyrate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,1</entry><entry valign="bottom" /><entry valign="bottom">0,1</entry></row><row><entry valign="bottom">3,4-methylenedioxycinnamic acid-N, N-diphenylamide or isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine, each 1% in 1,2-propylene glycol or 2,3, 4,5,6,10b, 11,12-octahydro-spiro [4b-aza-chrysen-12,2 '- [1,3] dithiolan -] - 1-one, 0.5% in 1,2-propylene glycol</entry><entry valign="bottom">%</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry><entry valign="bottom">0,5</entry></row><row><entry valign="bottom">Butylphenyacetate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">10</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Acetanisole</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">20</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Methyl sorbate</entry><entry valign="bottom">ppb</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">100</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">L-lysine</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">100</entry><entry valign="bottom">30</entry></row><row><entry valign="bottom">Malic acid</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">80</entry><entry valign="bottom" /></row><row><entry valign="bottom">L-arginine</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">5</entry><entry valign="bottom">20</entry></row><row><entry valign="bottom">L-aspartic acid</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /></row><row><entry valign="bottom">Calcium chloride</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">20</entry><entry valign="bottom" /></row><row><entry valign="bottom">Glutamine</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">2</entry><entry valign="bottom" /></row><row><entry valign="bottom">Potassium hydrogen phosphate</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">6</entry><entry valign="bottom" /></row><row><entry valign="bottom">Magnesium chloride</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">20</entry><entry valign="bottom" /></row><row><entry valign="bottom">L-valine</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,5</entry><entry valign="bottom" /></row><row><entry valign="bottom">Glycine</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">40</entry></row><row><entry valign="bottom">L-alanine</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">20</entry></row><row><entry valign="bottom">L-serine</entry><entry valign="bottom">ppm</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">50</entry></row><row><entry valign="bottom">water</entry><entry namest="col2" nameend="col10" align="left" valign="bottom">Ad 100</entry></row></tbody></tgroup></table></tables>

0517The substances were presented and made up to 100% with water and dissolved. If necessary, the product was bottled and carbonized.

Example S-36

0518Production of a fruit gum with a long-lasting fresh cooling taste using the cooling substances according to the invention.

0519Unless otherwise noted, all data in% by weight.<tables id="tabl0063" num="0063"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="86mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry><entry valign="top">6</entry></row></thead><tbody><row><entry /><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>water</entry><entry>23,6</entry><entry>23,6</entry><entry>23,6</entry><entry>23,6</entry><entry>23,6</entry><entry>23,6</entry></row><row><entry>Sucrose</entry><entry>34,5</entry><entry>34,5</entry><entry>34,5</entry><entry>34,5</entry><entry>34,5</entry><entry>34,5</entry></row><row><entry>Glucose Syrup, DE 40</entry><entry>31,89</entry><entry>31,89</entry><entry>31,89</entry><entry>31,89</entry><entry>31,89</entry><entry>31,89</entry></row><row><entry>Iso Syrup C * Tru Sweet 01750 (Cerestar GmbH)</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry><entry>1,5</entry></row><row><entry>Gelatin 240 Bloom</entry><entry>8,2</entry><entry>8,2</entry><entry>8,2</entry><entry>8,2</entry><entry>8,2</entry><entry>8,2</entry></row><row><entry>Yellow and red dye</entry><entry>0,01</entry><entry>0,01</entry><entry>0,01</entry><entry>0,01</entry><entry>0,01</entry><entry>0,01</entry></row><row><entry>Citric acid</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry><entry>0,2</entry></row><row><entry>Cherry flavor, containing 5% by weight of 3,4-methylenedioxycinnamic acid-N, N-diphenylamide, based on the flavor</entry><entry>0,1</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Cherry flavor, containing 5% by weight of 3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide based on the flavor</entry><entry /><entry>0,1</entry><entry /><entry /><entry /><entry /></row><row><entry>Cherry aroma, containing 2% by weight of 2,3,4,5,6,10b, 11,12-octahydrospiro [4b-azachrysen-12,2 '- [1,3] dithiolan-] -1-one based on the aroma</entry><entry /><entry /><entry>0,1</entry><entry /><entry /><entry /></row><row><entry>Cherry flavor, containing 2.5% by weight of 2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3 ] dithiolan] -1-one based on the aroma</entry><entry /><entry /><entry /><entry>0,1</entry><entry /><entry /></row><row><entry>Cherry flavor, containing 4% by weight of isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine based on the flavor</entry><entry /><entry /><entry /><entry /><entry>0,1</entry><entry /></row><row><entry>Cherry flavor, containing 5% by weight of cyclopentyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine based on the flavor</entry><entry /><entry /><entry /><entry /><entry /><entry>0,1</entry></row></tbody></tgroup></table></tables>

Example S-37

0520Production of sugar-containing and sugar-reduced carbonated soft drinks of the "Cola" flavor with a refreshing, long-lasting cooling effect using the cooling substances according to the invention.

0521Unless otherwise noted, all data in% by weight.<tables id="tabl0064" num="0064"><table frame="all"><tgroup cols="6"><colspec colnum="1" colname="col1" colwidth="91mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="15mm" /><thead><row><entry valign="top">component</entry><entry valign="top">1</entry><entry valign="top">2</entry><entry valign="top">3</entry><entry valign="top">4</entry><entry valign="top">5</entry></row></thead><tbody><row><entry>Phosphoric acid 85%</entry><entry>0,635</entry><entry>0,635</entry><entry>0,635</entry><entry>0,635</entry><entry>0,635</entry></row><row><entry>Citric acid, anhydrous</entry><entry>0,064</entry><entry>0,064</entry><entry>0,064</entry><entry>0,064</entry><entry>0,064</entry></row><row><entry>caffeine</entry><entry>0,064</entry><entry>0,064</entry><entry>0,064</entry><entry>0,064</entry><entry>0,064</entry></row><row><entry>Succrose</entry><entry>63,600</entry><entry>-</entry><entry>-</entry><entry>-</entry><entry>12,9</entry></row><row><entry>Sucralose</entry><entry>-</entry><entry>0,126</entry><entry>-</entry><entry>-</entry><entry>-</entry></row><row><entry>Erythritol</entry><entry>-</entry><entry>-</entry><entry>6,000</entry><entry>-</entry><entry>-</entry></row><row><entry>Aspartame</entry><entry>-</entry><entry>-</entry><entry>0,350</entry><entry>-</entry><entry>0,07</entry></row><row><entry>Stevioside</entry><entry>-</entry><entry>-</entry><entry>-</entry><entry>0,300</entry><entry>-</entry></row><row><entry>Acesulfame K</entry><entry>-</entry><entry>-</entry><entry>-</entry><entry>-</entry><entry>0,07</entry></row><row><entry>Sugar coloeur</entry><entry>0,800</entry><entry>0,800</entry><entry>0,800</entry><entry>0,800</entry><entry>0,800</entry></row><row><entry>Beverage emulsion type: cola</entry><entry>1,445</entry><entry>1,445</entry><entry>1,445</entry><entry>1,445</entry><entry>1,445</entry></row><row><entry>Sodium benzoate</entry><entry>0,106</entry><entry>0,106</entry><entry>0,106</entry><entry>0,106</entry><entry>0,106</entry></row><row><entry>3,4-methylenedioxy-cinnamic acid-N, N-diphenylamide</entry><entry>0,030</entry><entry>0,015</entry><entry /><entry /><entry>0,030</entry></row><row><entry>3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridyla-mid</entry><entry /><entry>0,015</entry><entry /><entry /><entry /></row><row><entry>Isopropyl- (5-methoxy-2-pyri-din-2-yl-pyrimidin-4-yl) amine</entry><entry /><entry /><entry>0,030</entry><entry /><entry /></row><row><entry>2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry /><entry /><entry /><entry>0,015</entry><entry /></row><row><entry>water</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry></row></tbody></tgroup></table></tables>

0522The solid components or ingredients are individually with water mixed, combined and made up to 100 g with water. The concentrate obtained is then aged overnight at room temperature. Finally, 1 part of the concentrate is mixed with 5 parts of carbonated water, bottled and sealed.

Example S-38

0523Production of chocolates with a long-lasting cooling taste using the cooling substances according to the invention.

0524Unless otherwise noted, all data in% by weight.<ol id="ol0008"><li><u>1</u> = dark chocolate</li><li><u>2</u> = low-calorie dark chocolate</li><li><u>3</u> = low-calorie dark chocolate</li><li><u>4</u> = low-calorie dark chocolate</li><li><u>5</u> = calorie-reduced whole milk chocolate</li></ol><tables id="tabl0065" num="0065"><table frame="all"><tgroup cols="6"><colspec colnum="1" colname="col1" colwidth="98mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="15mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><thead><row><entry valign="middle">component</entry><entry valign="middle"><u>1</u></entry><entry valign="middle"><u>2</u></entry><entry valign="middle"><u>3</u></entry><entry valign="middle"><u>4</u></entry><entry valign="middle"><u>5</u></entry></row></thead><tbody><row><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /></row><row><entry valign="middle">Cocoa butter</entry><entry valign="middle">13,5 0</entry><entry valign="middle">13,00</entry><entry valign="middle">13,50</entry><entry valign="middle">9,48</entry><entry valign="middle">14,00</entry></row><row><entry valign="middle">Cocoa mass</entry><entry valign="middle">42,0</entry><entry valign="middle">39,00</entry><entry valign="middle">42,00</entry><entry valign="middle">44,00</entry><entry valign="middle">23,00</entry></row><row><entry valign="middle">Erythritol</entry><entry valign="middle">-</entry><entry valign="middle">47,45</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry></row><row><entry valign="middle">Maltitol, crystalline</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">23,00</entry><entry valign="middle" /></row><row><entry valign="middle">Inulin</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">23,00</entry><entry valign="middle" /></row><row><entry valign="middle">Sorbitol</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">44,00</entry><entry valign="middle">-</entry><entry valign="middle">-</entry></row><row><entry valign="middle">Lactitol</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">38,55</entry></row><row><entry valign="middle">Polydextrose</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">9,70</entry></row><row><entry valign="middle">milk powder</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">14,0</entry></row><row><entry valign="middle">Sucrose</entry><entry valign="middle">43,9</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry><entry valign="middle">-</entry></row><row><entry valign="middle">Lecitin</entry><entry valign="middle">0,48</entry><entry valign="middle">0,48</entry><entry valign="middle">0,40</entry><entry valign="middle">0,48</entry><entry valign="middle">0,50</entry></row><row><entry valign="middle">Vanillin</entry><entry valign="middle">0,02</entry><entry valign="middle">0,02</entry><entry valign="middle">0,02</entry><entry valign="middle">0,02</entry><entry valign="middle">0,20</entry></row><row><entry valign="middle">Aspartame</entry><entry valign="middle">-</entry><entry valign="middle">0,03</entry><entry valign="middle">0,06</entry><entry valign="middle">-</entry><entry valign="middle">0,03</entry></row><row><entry valign="middle">3,4-methylenedioxy-cinnamic acid-N, N-diphenylamide</entry><entry valign="middle">0,01</entry><entry valign="middle">0,01</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /></row><row><entry valign="middle">2,3,4,5,6,10b, 11,12-octahydro spiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle">0,005</entry><entry valign="middle" /><entry valign="middle" /></row><row><entry valign="middle">Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="middle" /><entry valign="middle" /><entry valign="middle" /><entry valign="middle">0,0075</entry><entry valign="middle">0,01</entry></row></tbody></tgroup></table></tables>

Example S-39

0525Production of a beer mix beverage with a long-lasting fresh cooling taste: using the cooling substances according to the invention.

0526Unless otherwise noted, all data in% by weight.

The following were mixed:

0527<tables id="tabl0066" num="0066"><table frame="all"><tgroup cols="7"><colspec colnum="1" colname="col1" colwidth="82mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="14mm" /><colspec colnum="6" colname="col6" colwidth="14mm" /><colspec colnum="7" colname="col7" colwidth="14mm" /><thead><row><entry>component</entry><entry><u>1</u></entry><entry><u>2</u></entry><entry><u>3</u></entry><entry><u>4</u></entry><entry><u>5</u></entry><entry><u>6</u></entry></row></thead><tbody><row><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">sugar syrup</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry></row><row><entry valign="bottom">beer</entry><entry valign="bottom">50</entry><entry valign="bottom">50</entry><entry valign="bottom">50</entry><entry valign="bottom">50</entry><entry valign="bottom">50</entry><entry valign="bottom">50</entry></row><row><entry valign="bottom">Ethyl alcohol</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry><entry valign="bottom">4</entry></row><row><entry valign="bottom">citric acid</entry><entry valign="bottom">0,15</entry><entry valign="bottom">0,15</entry><entry valign="bottom">0,15</entry><entry valign="bottom">0,15</entry><entry valign="bottom">0,15</entry><entry valign="bottom">0,15</entry></row><row><entry valign="bottom">Ascorbic acid</entry><entry valign="bottom">0,01</entry><entry valign="bottom">0,01</entry><entry valign="bottom">0,01</entry><entry valign="bottom">0,01</entry><entry valign="bottom">0,01</entry><entry valign="bottom">0,01</entry></row><row><entry valign="bottom">Grapefruit juice</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry><entry valign="bottom">6</entry></row><row><entry valign="bottom">Grapefruit flavor, containing 2.5% 3,4-methylenedi-oxycinnamic acid-N, N-diphenylamide</entry><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Grapefruit flavor, containing 1% 2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-aza-chrysen-12,2 '- [1,3] dithiolan] - 1-on</entry><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Grapefruit flavor containing 1% 2,3,4,5,6,10b, 11,12-octahydro-3-methyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Grapefruit flavor containing 2% sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /><entry valign="bottom" /></row><row><entry valign="bottom">Grapefruit flavor containing 2.5% (5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) -isopropyl-amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry><entry valign="bottom" /></row><row><entry valign="bottom">Grapefruit flavor containing 2% (1,2-dimethyl-propyl) - (5-meth-oxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom" /><entry valign="bottom">0,2</entry></row><row><entry valign="bottom">water</entry><entry valign="bottom">ad 100</entry><entry valign="bottom">ad 100</entry><entry valign="bottom">ad 100</entry><entry valign="bottom">ad 100</entry><entry valign="bottom">ad 100</entry><entry valign="bottom">ad 100</entry></row><row><entry valign="bottom">carbonic acid</entry><entry valign="bottom">0,7</entry><entry valign="bottom">0,7</entry><entry valign="bottom">0,7</entry><entry valign="bottom">0,7</entry><entry valign="bottom">0,7</entry><entry valign="bottom">0,7</entry></row></tbody></tgroup></table></tables>

0528The effects found in the above application examples can be applied to all products of the respective product group, that is to say in particular toothpastes, chewing gums, mouthwashes, throat candies, gelatin capsules, chewy candies and tea in bags - if necessary by modifications which are not difficult to undertake by a person skilled in the art. It is readily apparent to the person skilled in the art on the basis of the present description that the compounds and mixtures according to the invention can be interchanged with one another with little effort, possibly with minor modifications. This means that the compound according to the invention used in the products of the application examples must also be understood as a placeholder for the other compounds and mixtures according to the invention. The concentration of the compound or mixture according to the invention used can also be varied in a manner which is readily recognizable to the person skilled in the art. In addition, the product-specific further constituents in the respective application example are easily understandable for the person skilled in the art and can also be exchanged for further product-typical constituents or supplemented by such. A variety of such product specific ingredients are disclosed in the description above.

0529The following examples illustrate the possible uses of the cooling substances to be used according to the invention in cosmetic formulations, the use of which on the skin makes it possible to feel cold and to calm the skin.

Examples S-40 - S-46

0530<ul id="ul0024" list-style="none"><li>S-40 = aerosol deodorant spray</li><li>S-41 = Sport Shower Gel</li><li>S-42 = After Shave Balm</li><li>S-43 = Eau de Toilette</li><li>S-44 = foot spray</li><li>S-45 = deodorant stick</li><li>S-46 = Deo APP Roll on Emulsion</li></ul><tables id="tabl0067" num="0067"><table frame="all"><tgroup cols="9"><colspec colnum="1" colname="col1" colwidth="41mm" /><colspec colnum="2" colname="col2" colwidth="46mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="11mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="12mm" /><colspec colnum="9" colname="col9" colwidth="12mm" /><thead><row><entry valign="top">raw material</entry><entry valign="top">INCI name</entry><entry valign="top" /><entry namest="col4" nameend="col5" align="left" valign="top" /><entry namest="col6" nameend="col7" align="left" valign="top">example</entry><entry valign="top" /><entry valign="top" /></row><row><entry valign="top" /><entry valign="top" /><entry valign="top">S-40</entry><entry valign="top">S-41</entry><entry valign="top">S-42</entry><entry valign="top">S-43</entry><entry valign="top">S-44</entry><entry valign="top">S-45</entry><entry valign="top">S-46</entry></row><row><entry valign="top" /><entry valign="top" /><entry namest="col3" nameend="col9" align="left" valign="top">% By weight</entry></row></thead><tbody><row><entry>3,4-methylenedioxycinnamic acid-N, N-diphenylamide</entry><entry /><entry /><entry /><entry>0,1</entry><entry>0,1</entry><entry /><entry>0,1</entry><entry /></row><row><entry>3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridylamide</entry><entry /><entry /><entry>0,15</entry><entry /><entry /><entry /><entry /><entry>0,2</entry></row><row><entry>Cyclopentyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry /><entry>0,15</entry><entry /><entry /><entry /><entry>0,1</entry><entry /><entry /></row><row><entry>sec-butyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry /><entry /><entry>0,05</entry><entry>0,1</entry><entry /><entry /><entry>0,1</entry><entry /></row><row><entry>2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry /><entry>0,05</entry><entry /><entry /><entry /><entry /><entry /><entry>0,05</entry></row><row><entry>2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithian] -1-one</entry><entry /><entry /><entry /><entry /><entry>0,05</entry><entry>0,05</entry><entry /><entry /></row><row><entry>Allantoin</entry><entry>Allantoin</entry><entry /><entry /><entry>0,1</entry><entry /><entry /><entry /><entry /></row><row><entry>(-) Alpha Bisabolol Natural</entry><entry>Bisabolol</entry><entry>0,1</entry><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Abil 350</entry><entry>Dimethicone</entry><entry /><entry /><entry>3,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Akyposoft 100 BVC</entry><entry>Sodium Laureth-11 carboxylate, Laureth-10</entry><entry /><entry>8,5</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Aloe vera gel concentrate 10: 1</entry><entry>Aloe Barbadensis Leaf Juice</entry><entry /><entry /><entry /><entry /><entry /><entry>1,0</entry><entry /></row><row><entry>Arlypon F</entry><entry>Laureth-2</entry><entry /><entry>2,5</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Carbopol Ultrez-21</entry><entry>Acrylates / C 10-30 alkyl acrylate crosspolymer</entry><entry /><entry /><entry>0,4</entry><entry /><entry /><entry /><entry /></row><row><entry>Covi-Ox T-70</entry><entry>Tocopherol</entry><entry /><entry /><entry>0,1</entry><entry /><entry /><entry /><entry /></row><row><entry>Dehyton K</entry><entry>Cocoamidopropyl betaines</entry><entry /><entry>7,0</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Deolite</entry><entry>Dimethyl phenylpropanol pentylene glycol</entry><entry /><entry /><entry /><entry /><entry /><entry>0,5</entry><entry>0,5</entry></row><row><entry>Dow Corning 246 fluid</entry><entry>Cyclohexasiloxanes</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>1,0</entry></row><row><entry>D-Panthenol 75 L.</entry><entry>Panthenol</entry><entry /><entry /><entry>1,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Dracorin® 100 SEP</entry><entry>Glyceryl stearate, PEG-100 stearate</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>0,5</entry></row><row><entry>Dracorin® GOC</entry><entry>Glyceryl Oleate Citrate Caprylic Capric Triglyceride</entry><entry /><entry /><entry /><entry /><entry /><entry>2,0</entry><entry>2,0</entry></row><row><entry>Dragocide® Liquid</entry><entry>Phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben, isobutylparaben</entry><entry /><entry>0,5</entry><entry>0,8</entry><entry /><entry /><entry /><entry>0,8</entry></row><row><entry>Dragosantol® 100</entry><entry>Bisabolol</entry><entry /><entry /><entry>0,2</entry><entry /><entry>0,2</entry><entry /><entry>0,2</entry></row><row><entry>Dragoxat® 89</entry><entry>Ethylhexyl isononanoate</entry><entry /><entry /><entry /><entry /><entry /><entry>1,0</entry><entry /></row><row><entry>EDTA BD</entry><entry>Disodium EDTA</entry><entry /><entry /><entry>0,1</entry><entry /><entry /><entry /><entry /></row><row><entry>Ethanol 96%</entry><entry>Ethanol</entry><entry>27,5</entry><entry /><entry /><entry>81,0</entry><entry>45,0</entry><entry /><entry /></row><row><entry>Extrapone® Ginkgo Biloba</entry><entry>Propylene Glycol, Water (Aqua), Ginkgo Biloba Leaf Extract, Glucose, Lactic Acid</entry><entry /><entry>1,0</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Farnesol</entry><entry>Farnesol</entry><entry /><entry /><entry /><entry /><entry>0,5</entry><entry /><entry /></row><row><entry>Fragrance</entry><entry>Perfume</entry><entry>1,0</entry><entry>1,5</entry><entry>1,0</entry><entry>10,0</entry><entry>0,5</entry><entry>0,5</entry><entry>0,4</entry></row><row><entry>Frescolat® MGA</entry><entry>Menthone Glycerin Acetal</entry><entry /><entry /><entry /><entry /><entry /><entry>0,8</entry><entry /></row><row><entry>Frescolat® ML</entry><entry>Menthyl lactate</entry><entry /><entry>0,4</entry><entry>0,8</entry><entry /><entry>0,2</entry><entry /><entry>0,3</entry></row><row><entry>Genapol LRO Liquid</entry><entry>Sodium Laureth Sulfate</entry><entry /><entry>40,0</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Glycerin 99.5%</entry><entry>Glycerin</entry><entry /><entry>2,5</entry><entry>2,5</entry><entry /><entry /><entry>4,0</entry><entry>4,0</entry></row><row><entry>Isodragol®</entry><entry>Triisononanoin</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>1,0</entry></row><row><entry>Jojoba Oil</entry><entry>Simmondsia Chinensis (Jojoba) Seed Oil</entry><entry /><entry /><entry>2,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Sodium hydroxide 10% solution.</entry><entry>ISodium hydroxides</entry><entry /><entry>0,1</entry><entry>0,8</entry><entry /><entry /><entry /><entry>0,6</entry></row><row><entry>Sodium stearate</entry><entry>Sodium stearate</entry><entry /><entry /><entry /><entry /><entry /><entry>9,0</entry><entry /></row><row><entry>Neutral oil</entry><entry>Caprylic / Capric triglycerides</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>3,5</entry></row><row><entry>PCL -Liquid100</entry><entry>Cetearyl ethyl hexanoate</entry><entry /><entry /><entry>3,0</entry><entry /><entry>1,0</entry><entry /><entry /></row><row><entry>Pemulen TR-2</entry><entry>Acrylates / C10-30 alkyl acrylate crosspolymer</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>0,3</entry></row><row><entry>Polymer JR400</entry><entry>Polyquaternium-10</entry><entry /><entry>0,3</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Propane butane 2.7 bar</entry><entry>Propanes, butanes</entry><entry>70,2</entry><entry /><entry /><entry /><entry>49,5</entry><entry /><entry /></row><row><entry>Propylene glycol</entry><entry>Propylene glycol</entry><entry /><entry /><entry /><entry /><entry /><entry>36,5</entry><entry /></row><row><entry>Rezal 36 GP</entry><entry>Aluminum zirconium tetrachlorohydrex GLY</entry><entry /><entry /><entry /><entry /><entry /><entry /><entry>5,0</entry></row><row><entry>Solubilizer</entry><entry>PEG-40 Hydrogenated Castor Oil, Trideceth-9, Propylene Glycol, Water (Aqua)</entry><entry /><entry>0,5</entry><entry /><entry>1,0</entry><entry>1,0</entry><entry /><entry /></row><row><entry>SymAmide UDA</entry><entry>Undecylenamide DEA, Diethanolamine</entry><entry /><entry /><entry /><entry /><entry>1,0</entry><entry /><entry /></row><row><entry>SymCalmin®</entry><entry>Pentylene Glycol, Butylene Glycol, Hydroxyphenyl Propamidobenzoic Acid</entry><entry /><entry /><entry>0,5</entry><entry /><entry /><entry /><entry /></row><row><entry>SymClariol®</entry><entry>Decylene glycol</entry><entry>0,5</entry><entry /><entry /><entry /><entry>0,5</entry><entry /><entry /></row><row><entry>SymDeo® MPP</entry><entry>Dimethyl phenylbutanol</entry><entry>0,5</entry><entry /><entry /><entry /><entry /><entry /><entry>0,5</entry></row><row><entry>SymMollient® W / S</entry><entry>Trideceth-9, PEG-5 isononanoates</entry><entry /><entry /><entry /><entry>1,0</entry><entry>0,5</entry><entry /><entry /></row><row><entry>SymRelief®</entry><entry>Bisabolol, Zingiber Officinale (Ginger) Root Extract</entry><entry /><entry>0,2</entry><entry>0,2</entry><entry /><entry /><entry /><entry /></row><row><entry>SymVital ™</entry><entry>Aloe Barbadensis Leaf Juice Powder, Magnesium Ascorbyl Phosphate, Rubus Idaeus (Raspberry) Leaf Extract</entry><entry /><entry /><entry>0,1</entry><entry /><entry /><entry /><entry /></row><row><entry>Vitamin E acetate</entry><entry>Tocopherol Acetate</entry><entry /><entry /><entry>0,5</entry><entry /><entry /><entry /><entry /></row><row><entry>water</entry><entry>Water (aqua)</entry><entry /><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad</entry><entry>ad 10</entry><entry>ad 100</entry></row></tbody></tgroup></table></tables>

Examples S-47 - S-52

0531<ul id="ul0025" list-style="none"><li>S-47 = day cream O / W, approx. SPF 15</li><li>S-48 = sun protection emulsion approx. SPF 25</li><li>S-49 = After Sun Spray</li><li>S-50 = after shave</li><li>S-51 = Creme W / O</li><li>S-52 = hair conditioner</li></ul><tables id="tabl0068" num="0068"><table frame="all"><tgroup cols="8"><colspec colnum="1" colname="col1" colwidth="45mm" /><colspec colnum="2" colname="col2" colwidth="54mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="11mm" /><colspec colnum="6" colname="col6" colwidth="12mm" /><colspec colnum="7" colname="col7" colwidth="12mm" /><colspec colnum="8" colname="col8" colwidth="11mm" /><thead><row><entry valign="top">raw material</entry><entry valign="top">INCI name</entry><entry namest="col3" nameend="col8" align="left" valign="top">Examples</entry></row><row><entry valign="top" /><entry valign="top" /><entry valign="top">S-47</entry><entry valign="top">S-48</entry><entry valign="top">S-49</entry><entry valign="top">S-50</entry><entry valign="top">S-51</entry><entry valign="top">S-52</entry></row><row><entry valign="top" /><entry valign="top" /><entry namest="col3" nameend="col8" align="left" valign="top">% By weight</entry></row></thead><tbody><row><entry>3,4-methylenedioxycinnamic acid-N-cyclohexyl-N-2-pyridyla-mid</entry><entry /><entry>0;1</entry><entry /><entry>0,1</entry><entry /><entry /><entry /></row><row><entry>2,3,4,5,6,10b, 11,12-octahydro-3,3-dimethyl-spiro [4b-aza-chrysen-12,2 '- [1,3] dithiolan] -1-one</entry><entry /><entry>0,05</entry><entry>0,05</entry><entry /><entry /><entry>0,05</entry><entry>0,1</entry></row><row><entry>Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry /><entry /><entry>0,25</entry><entry>0,2</entry><entry /><entry /><entry /></row><row><entry>Cyclopentyl- (5-ethyl-2-pyridin-2-yl-pyrimidin-4-yl) amine</entry><entry /><entry /><entry /><entry /><entry>0,1</entry><entry>0,1</entry><entry>0,2</entry></row><row><entry>Allantoin</entry><entry>Allantoin</entry><entry /><entry /><entry>0,1</entry><entry /><entry /><entry /></row><row><entry>(-) Alpha Bisabolol Natural</entry><entry>Bisabolol</entry><entry /><entry /><entry>0,2</entry><entry /><entry>0,3</entry><entry /></row><row><entry>Abil 350</entry><entry>Dimethicone</entry><entry>2,0</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Aluminum stearate</entry><entry>Aluminum stearate</entry><entry /><entry /><entry /><entry /><entry>1,2</entry><entry /></row><row><entry>Arlypon F</entry><entry>Laureth-2</entry><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Biotive® L-Arginine</entry><entry>Arginine</entry><entry /><entry>0,5</entry><entry /><entry /><entry /><entry /></row><row><entry>Carbopol Ultrez-10</entry><entry>Carbomer</entry><entry>0,2</entry><entry /><entry>0,2</entry><entry /><entry /><entry /></row><row><entry>Covi-Ox T-70</entry><entry>Tocopherol</entry><entry /><entry /><entry /><entry>0,1</entry><entry /><entry /></row><row><entry>Cutina GMS V</entry><entry>Glyceryl stearate</entry><entry>2,0</entry><entry /><entry>2,0</entry><entry /><entry /><entry /></row><row><entry>Dehyquart A CA</entry><entry>Cetrimonium chloride</entry><entry /><entry /><entry /><entry /><entry /><entry>4,0</entry></row><row><entry>Dow Corning 246 fluid</entry><entry>Cyclohexasiloxanes</entry><entry /><entry /><entry /><entry>2,0</entry><entry /><entry /></row><row><entry>D-Panthenol 75 L.</entry><entry>Panthenol</entry><entry /><entry /><entry /><entry>1,0</entry><entry /><entry>1,0</entry></row><row><entry>Dracorin® CE</entry><entry>Glyceryl stearate / citrate</entry><entry /><entry>2,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Dracorin® GOC</entry><entry>Glyceryl Oleate Citrate Caprylic Capric Triglyceride</entry><entry /><entry /><entry /><entry>2,0</entry><entry /><entry /></row><row><entry>Drago beta glucan</entry><entry>Water (Aqua), Butylene Glycol, Glycerin, Avena Sativa (Oat) Kernel Extract</entry><entry /><entry /><entry>2,0</entry><entry /><entry /><entry /></row><row><entry>DragoCalm®</entry><entry>Water, Glycerin, Avena Sativa (Oat Kernel Extract)</entry><entry /><entry /><entry>1,0</entry><entry /><entry /><entry /></row><row><entry>Dragocide® Liquid</entry><entry>Phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben, isobutylparaben</entry><entry>0,8</entry><entry /><entry /><entry /><entry>0,8</entry><entry>0,8</entry></row><row><entry>Dragoderm®</entry><entry>Glycerin, Triticum Vulgare (Wheat) Gluten, Water (Aqua)</entry><entry /><entry /><entry>2,0</entry><entry>2,0</entry><entry /><entry>2,0</entry></row><row><entry>Dragosan W / OP</entry><entry>Sorbitan Isostearate, Hydrogenated Castor Oil, Ceresin, Beeswax (Cera Alba)</entry><entry /><entry /><entry /><entry /><entry>8,0</entry><entry /></row><row><entry>Dragosine®</entry><entry>Carnosine</entry><entry /><entry /><entry>0,2</entry><entry /><entry /><entry /></row><row><entry>Dragoxat® 89</entry><entry>Ethylhexyl isononanoate</entry><entry /><entry>3,0</entry><entry>4,0</entry><entry>1,0</entry><entry>5,0</entry><entry /></row><row><entry>EDTA BD</entry><entry>Disodium EDTA</entry><entry /><entry>0,1</entry><entry>0,1</entry><entry /><entry /><entry /></row><row><entry>Emulsiphos®</entry><entry>Potassium Cetyl Phosphate, Hydrogenated Palm Glycerides</entry><entry>2,0</entry><entry /><entry>2,0</entry><entry /><entry /><entry /></row><row><entry>Ethanol 96%</entry><entry>Ethanol</entry><entry /><entry /><entry /><entry>65,0</entry><entry /><entry /></row><row><entry>Farnesol</entry><entry>Farnesol</entry><entry /><entry /><entry /><entry /><entry /><entry /></row><row><entry>Fragrance</entry><entry>Perfume</entry><entry>0,3</entry><entry>0,4</entry><entry>0,3</entry><entry>1,0</entry><entry>0,3</entry><entry>0,3</entry></row><row><entry>Frescolat® ML</entry><entry>Menthyl lactate</entry><entry>0,2</entry><entry /><entry /><entry>0,3</entry><entry /><entry /></row><row><entry>Fruitapone® Orange B</entry><entry>Propylene Glycol, Water (Aqua), Citric Acid, Citrus Aurantium Dulcis (Orange) Juice, Trideceth-9, Bisabolol</entry><entry>1,0</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Glycerin 99.5%</entry><entry>Glycerin</entry><entry>2,0</entry><entry /><entry>3,0</entry><entry>4,0</entry><entry>3,0</entry><entry /></row><row><entry>Hydrolite®-5</entry><entry>Pentylene glycol</entry><entry /><entry>5,0</entry><entry /><entry>5,0</entry><entry /><entry /></row><row><entry>Hydroviton®-24</entry><entry>Water, Pentylene Glycol, Glycerin, Lactic Acid, Sodium Lactate, Serine, Urea, Sorbitol, Sodium Chloride, Allantoin</entry><entry /><entry /><entry>1,0</entry><entry /><entry>2,0</entry><entry /></row><row><entry>Iso adipate</entry><entry>Diisopropyl adipate</entry><entry /><entry /><entry>1,0</entry><entry>5,0</entry><entry /><entry /></row><row><entry>Jojoba Oil</entry><entry>Simmondsia Chinensis (Jojoba) Seed Oil</entry><entry /><entry /><entry /><entry /><entry>2,0</entry><entry /></row><row><entry>Keltrol CG RD</entry><entry>Xanthan gum</entry><entry>0,1</entry><entry>0,1</entry><entry>0,2</entry><entry /><entry /><entry /></row><row><entry>Lanette O</entry><entry>Cetearyl alcohol</entry><entry>3,0</entry><entry>2,0</entry><entry>3,0</entry><entry /><entry /><entry>3,5</entry></row><row><entry>Mineral Oil</entry><entry>Mineral Oil</entry><entry /><entry /><entry /><entry /><entry>8,0</entry><entry /></row><row><entry>Sodium chloride</entry><entry>Sodium chloride</entry><entry /><entry /><entry /><entry /><entry>1,0</entry><entry>2,0</entry></row><row><entry>Sodium hydroxide 10% solution.</entry><entry>Sodium hydroxides</entry><entry>0,5</entry><entry /><entry /><entry /><entry>0,4</entry><entry /></row><row><entry>Neo Heliopan® 303</entry><entry>Octocrylene</entry><entry>5,0</entry><entry>8,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Neo Heliopan® 357</entry><entry>Butylmethoxydibenzoylmethane</entry><entry>1,1</entry><entry>3,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Neo Heliopan® HMS</entry><entry>Homo salads</entry><entry /><entry>5,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Neo Heliopan® Hydro, 25% solution, neutralized with Biotive L-arginine</entry><entry>Phenylbenzimidazole sulfonic acid</entry><entry>3,0</entry><entry>8,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Neo Heliopan®AP, 10% solution, neutralized with NAOH</entry><entry>Disodium Phenyl Dibenzimidazole Tetrasulfonate</entry><entry>3,0</entry><entry>13,3</entry><entry /><entry /><entry /><entry /></row><row><entry>Neo Heliopan® OS</entry><entry>Ethylhexyl salicylate</entry><entry>5,0</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Neutral oil</entry><entry>Caprylic / Capric triglycerides</entry><entry /><entry /><entry /><entry>5,0</entry><entry /><entry /></row><row><entry>Ozokerite Wax 2389</entry><entry>Ozokerite</entry><entry /><entry /><entry /><entry /><entry>2,0</entry><entry /></row><row><entry>Pemulen TR-2</entry><entry>Acrylates / C10-30 Alkyl Acrylate Cross polymer</entry><entry /><entry /><entry /><entry>0,3</entry><entry /><entry /></row><row><entry>Polyquart H81</entry><entry>PEG-15 Coco Polyamine</entry><entry /><entry /><entry /><entry /><entry /><entry>3,0</entry></row><row><entry>Propylene glycol</entry><entry>Propylene glycol</entry><entry>3,0</entry><entry>4,0</entry><entry /><entry /><entry /><entry /></row><row><entry>Softisan 100</entry><entry>Hydrogenated Coco Glycerides</entry><entry /><entry>1,5</entry><entry /><entry /><entry /><entry /></row><row><entry>Squalane, Vegetable Based</entry><entry>Squalane</entry><entry /><entry /><entry>3,0</entry><entry /><entry /><entry /></row><row><entry>SymCalmin®</entry><entry>Pentylene Glycol, Butylene Glycol, Hyd roxyphenyl Propamidobenzoic Acid</entry><entry /><entry /><entry>1,0</entry><entry /><entry /><entry /></row><row><entry>SymDiol® 68</entry><entry>1,2 hexanediol, caprylyl glycol</entry><entry /><entry /><entry>1,0</entry><entry /><entry /><entry /></row><row><entry>SymGlucan®</entry><entry>Water (aqua) glycerin, beta glucan</entry><entry /><entry /><entry /><entry>1,0</entry><entry /><entry /></row><row><entry>SymMollient® W / S</entry><entry>Trideceth-9, PEG-5 isononanoates</entry><entry /><entry /><entry /><entry>0,5</entry><entry /><entry /></row><row><entry>SymRelief®</entry><entry>Bisabolol, Zingiber Officinale (Ginger) Root Extract</entry><entry /><entry /><entry /><entry>0,2</entry><entry /><entry /></row><row><entry>SymRepair®</entry><entry>Hexyldecanol, Bisabolol, Cetylhydroxyproline Palmitamide, Stearic Acid, Brassica Campestris (Rapeseed Sterols)</entry><entry /><entry /><entry>2,0</entry><entry>3,0</entry><entry /><entry /></row><row><entry>SymVital ™</entry><entry>Aloe Barbadensis Leaf Juice Powder, Magnesium Ascorbyl Phosphate, Rubus Idaeus (Raspberry) Leaf Extract</entry><entry>0,3</entry><entry /><entry /><entry /><entry /><entry /></row><row><entry>Triethanolamine 99%</entry><entry>Triethanolamine</entry><entry /><entry /><entry>0,4</entry><entry>0,3</entry><entry /><entry /></row><row><entry>Vitamin E acetate</entry><entry>Tocopherol Acetate</entry><entry /><entry>0,5</entry><entry /><entry /><entry>0,2</entry><entry /></row><row><entry>water</entry><entry>Water (aqua)</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry><entry>ad 100</entry></row></tbody></tgroup></table></tables>

Test Example 1: Investigation of active substances according to the invention in the assay on TRPM8 modulators

0532Various active substances according to the invention were examined in the assay according to reference example 3.

0533The EC50 values ​​of modulators according to the invention that are determined are summarized in Tables A, B and C below.<tables id="tabl0069" num="0069"><table frame="all"><title>Table A:</title><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="42mm" /><colspec colnum="3" colname="col3" colwidth="100mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><thead><row><entry valign="top">No.</entry><entry valign="top">Structure type 1</entry><entry valign="top">Physical data</entry><entry valign="top">EC50</entry></row></thead><tbody><row rowsep="0"><entry>1-1</entry><entry><chemistry id="chem0147" num="0147"><img file="EP3663366A2_D0147.tif" /></chemistry></entry><entry morerows="1" rowsep="1">¹H-NMR (CDCl₃): m 7.12-7.33; d 4.70; m 4.10-4.20: m 4.00-4.10; m 3.60-3.69; m 3.38-3.48; m 3.14-3.23; m 2.96-3.04; m 2.76-2.85; m 2.59-2.68; m 2.36-2.48; m 2.23-2.34; m 1.95-2.04; m 1.84-1.95 [ppm]</entry><entry morerows="1" rowsep="1">0.1 µM</entry></row><row><entry /><entry><patcit id="pcit0082" dnum="lu5088140"><text>LU 5088140</text></patcit></entry></row><row rowsep="0"><entry>1-2</entry><entry><chemistry id="chem0148" num="0148"><img file="EP3663366A2_D0148.tif" /></chemistry></entry><entry morerows="1" rowsep="1">¹H-NMR (CDCl₃): m 7.10-7.32; d 4.68; m 4.08-4.20; dtr 4.04; m 3.56-3.65; m 3.35-3.50; dtr 3.19; m 2.93-3.05; m 2.74-2.86; m 2.34-2.46; s 2.23; s 1.10; s 1.08 [ppm]</entry><entry morerows="1" rowsep="1">0.6 µM</entry></row><row><entry /><entry><patcit id="pcit0083" dnum="lu5040212"><text>LU 5040212</text></patcit></entry></row><row rowsep="0"><entry>1-3</entry><entry><chemistry id="chem0149" num="0149"><img file="EP3663366A2_D0149.tif" /></chemistry></entry><entry morerows="1" rowsep="1">¹H-NMR (CDCl₃): m 7.14-7.34; m 4.90-5.02; m 4.63-4.74; m 3.87-3.99; m 3.56-3.68; m 3.30-3.48; 2.96-3.08; m 2.78-2.92; d 2.66; m 2.26-2.43; d 1.54 [ppm]</entry><entry morerows="1" rowsep="1">0.7 µM</entry></row><row><entry /><entry><patcit id="pcit0084" dnum="lu5040211"><text>LU 5040211</text></patcit></entry></row><row><entry>1-4</entry><entry><chemistry id="chem0150" num="0150"><img file="EP3663366A2_D0150.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m7.12-7.34; d 4.90; m 4.04-4.16; m 2.94-3.32; m 2.78-2.88; m 2.62-2.64; m 2.40-2.50; m 2.24-2.34; m 1.81-2.20 [ppm]</entry><entry>3.1 µM</entry></row><row><entry>1-5</entry><entry><chemistry id="chem0151" num="0151"><img file="EP3663366A2_D0151.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m7.28-7.32; m 7.20-7.26; d 7.17; d 4.86; m4.02-4.09; m3.14-3.30; m 2.94-3.09; m 2.79-2.86; m 2.63-2.71; m 2.35-2.44; s 2.24; tr 2.17; m 2.00-2.14; d 1.08 [ppm]</entry><entry>1.4 µM</entry></row><row><entry>1-6</entry><entry><chemistry id="chem0152" num="0152"><img file="EP3663366A2_D0152.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m 7.16-7.34; q 5.06; q 5.00; d 4.86; m 3.62-3.74; m 3.35-3.46; m 3.13-3.31; m 2.94-3.12; m 2.70-2.92; m 1.98-2.14; d 1.54 [ppm]</entry><entry>0.2 µM</entry></row><row><entry>1-7</entry><entry><chemistry id="chem0153" num="0153"><img file="EP3663366A2_D0153.tif" /></chemistry></entry><entry>Diastereomers: ¹H-NMR (CDCl₃): m 7.14-7.42; m 5.18-5.27; d 4.99; d 4.74; m 4.30-4.46; m 4.16-4.25; m 3.99-4.08; m 3.67-3.91; tr 3.49; m 3.19-3.33; m 2.98-3.14; m 2.84-2.93; tr 2.18; tr 1.98; m 1.44-1.69 [ppm]</entry><entry>0.7 µM</entry></row><row><entry>1-8</entry><entry><chemistry id="chem0154" num="0154"><img file="EP3663366A2_D0154.tif" /></chemistry></entry><entry>Diastereomers: ¹H-NMR (CDCl₃): m 7.40-7.46; m 7.20-7.33; m 7.12-7.19; d 4.97; m 4.22-4.44; m 4.09-4.17; m 3.87-3.97; m 3.80-3.87; m 3.60-3.67; tr 3.35; tr 3.22; m 2.93-3.11; m 2.72-2.92; d 2.68; dd 2.54; d 2.39; m 2.14-2.34; tr 1.98; s 1.44; m 1.10-1.25 [ppm]</entry><entry>9.8 µM</entry></row><row><entry>1-9</entry><entry><chemistry id="chem0155" num="0155"><img file="EP3663366A2_D0155.tif" /></chemistry></entry><entry>Diastereomers: ¹H-NMR (CDCl₃): m 7.20-7.40; q 5.50; q 5.40; m 5.06-5.22; m 3.93-4.03; m 3.77-3.86; m 3.43-3.58; m 3.28-3.43; m 3.00-3.14; m 2.86-3.00; m 2.43-2.72; tr 1.50 [ppm]</entry><entry>10th µM</entry></row></tbody></tgroup></table></tables><tables id="tabl0070" num="0070"><table frame="all"><title>Table B:</title><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="12mm" /><colspec colnum="2" colname="col2" colwidth="57mm" /><colspec colnum="3" colname="col3" colwidth="78mm" /><colspec colnum="4" colname="col4" colwidth="19mm" /><thead><row><entry valign="top">No.</entry><entry valign="top">Structure type 2</entry><entry valign="top">Physical data</entry><entry valign="top">EC₅₀</entry></row></thead><tbody><row><entry>2-1</entry><entry><chemistry id="chem0156" num="0156"><img file="EP3663366A2_D0156.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 8.77; d 8.39; s 7.91; m 7.26-7.32; d 5.17; m 5.42-5.54; s 3.94 d 1.32 [ppm]</entry><entry>0.1 µM</entry></row><row><entry>2-2</entry><entry><chemistry id="chem0157" num="0157"><img file="EP3663366A2_D0157.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.74; d 8.40; s 7.88; tr 7.74; m 7.20-7.32; s 5.32; m 4.48-4.60; s 3.88; m 2.08-2.24; m 1.46-1.84 [ppm]</entry><entry>0.3 µM</entry></row><row><entry>2-3</entry><entry><chemistry id="chem0158" num="0158"><img file="EP3663366A2_D0158.tif" /></chemistry></entry><entry>Retention time (HPLC): 2.645 min; Method 1 in the Appendix</entry><entry>0.8 µM</entry></row><row><entry>2-4</entry><entry><chemistry id="chem0159" num="0159"><img file="EP3663366A2_D0159.tif" /></chemistry></entry><entry>Retention time (HPLC): 4.02 min; Method 2 in the Appendix</entry><entry>1.0 µM</entry></row><row><entry>2-5</entry><entry><chemistry id="chem0160" num="0160"><img file="EP3663366A2_D0160.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.74; d 8.38; s 7.90; tr 7.75; d 5.16; m 4.27-4.38; s 3.90; m 1.57-1.72; d 1.28; tr 0.98 [ppm]</entry><entry>0.1 µM</entry></row><row><entry>2-7</entry><entry><chemistry id="chem0161" num="0161"><img file="EP3663366A2_D0161.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 8.74; d 8.37; s 7.90; tr 7.76; m 7.24-7.30; d 5.20; m 4.25-4.36; s 3.92; m 1.88-1.98; d 1.22; d 1.00; d 0.97 [ppm]</entry><entry>0.1 µM</entry></row><row><entry>2-8</entry><entry><chemistry id="chem0162" num="0162"><img file="EP3663366A2_D0162.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 8.74; d 8.37; s 7.90; tr 7.76; m 7.24-7.30; d 5.20; m 4.25-4.36; s 3.92; m 1.88-1.98; d 1.22; d 1.00; d 0.97 [ppm]</entry><entry>0.5 µM</entry></row><row><entry>2-9</entry><entry><chemistry id="chem0163" num="0163"><img file="EP3663366A2_D0163.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.56; d 8.24; s 7.73; tr 7.67; m 7.15-7.22; m 5.50-5.61; d 5.50; m 4.48-4.60, s 3.83; br s 3.49; m 1.78-1.88; m 1.40-1.49; d 1.24 [ppm]</entry><entry>1.0 µM</entry></row><row><entry>2-10</entry><entry><chemistry id="chem0164" num="0164"><img file="EP3663366A2_D0164.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 8.76; d 8.38; s 7.91; tr 7.76; m 7.24-7.30; d 5.54; m 4.55-4.64; s 3.89; d 3.51; s 3.39; d 1.35 [ppm]</entry><entry>2.2 µM</entry></row><row><entry morerows="1">2-11</entry><entry morerows="1"><chemistry id="chem0165" num="0165"><img file="EP3663366A2_D0165.tif" /></chemistry></entry><entry rowsep="0">HPLC retention time: 2.41 min</entry><entry morerows="1">1.2 µM</entry></row><row><entry>HPLC method 1: see Appendix</entry></row><row><entry>2-12</entry><entry><chemistry id="chem0166" num="0166"><img file="EP3663366A2_D0166.tif" /></chemistry></entry><entry>1H NMR (CDCl3): d 8.79; m 8.32-8.38; tr 7.82; m 7.31-7.36; m 5.62-5.72; s 3.98; dd 1.50 [ppm]</entry><entry>3.2 µM</entry></row><row><entry>2-13</entry><entry><chemistry id="chem0167" num="0167"><img file="EP3663366A2_D0167.tif" /></chemistry></entry><entry>Retention time (HPLC): 4.92 min; Method 2 in the Appendix</entry><entry>11.7 µM</entry></row><row><entry>2-14</entry><entry><chemistry id="chem0168" num="0168"><img file="EP3663366A2_D0168.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 8.77; d 8.43; s 8.20; tr 7.78; tr 7.30; m 4.49-4.60; q 2.41; d 1.30; tr 1.25 [ppm]</entry><entry>0.4 µM</entry></row><row><entry>2-15</entry><entry><chemistry id="chem0169" num="0169"><img file="EP3663366A2_D0169.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.71; d 8.30; tr 7.95; s 7.91; tr 7.49; d 7.20; m 4.46-4.56; s 3.94; dd 2.72; d 1.26 [ppm]</entry><entry>0.8 µM</entry></row><row><entry>2-16</entry><entry><chemistry id="chem0170" num="0170"><img file="EP3663366A2_D0170.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.70; d 8.30; m 7.90-7.97; tr 7.46; d 7.00; s 6.68; m 4.46-4.56; s 3.94; d 1.26 [ppm]</entry><entry>1.6 µM</entry></row><row><entry>2-17</entry><entry><chemistry id="chem0171" num="0171"><img file="EP3663366A2_D0171.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.70; d 8.29; m 7.90-7.97; tr 7.46; d 6.98; m 4.46-4.56; tr 4.28; s 3.93; dd 2.66; m 2.44-2.57; d 1.25 [ppm]</entry><entry>0.4 µM</entry></row><row><entry>2-18</entry><entry><chemistry id="chem0172" num="0172"><img file="EP3663366A2_D0172.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.71; d 8.30; m 7.90-8.00; tr 7.48; d 7.04; br s 5.54; m 4.46-4.57; s 4.33; s 3.95; d 1.26 [ppm]</entry><entry>0.5 µM</entry></row><row><entry>2-19</entry><entry><chemistry id="chem0173" num="0173"><img file="EP3663366A2_D0173.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.70; d 8.30; s 7.96; tr 7.91; tr 7.43; d 6.78; m 4.46-4.56; s 3.94; s 2.49; d 1.25 [ppm]</entry><entry>0.3 µM</entry></row><row><entry>2-20</entry><entry><chemistry id="chem0174" num="0174"><img file="EP3663366A2_D0174.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): br s 9.55; s 8.80; d 8.35; s 7.97; tr 7.78; tr 7.31; d 5.26; m 4.49-4.58; s 3.91; tr 2.34; m 1.61-1.70; m 1.20-1.41; tr 0.88 [ppm]</entry><entry>0.9 µM</entry></row><row><entry>2-21</entry><entry><chemistry id="chem0175" num="0175"><img file="EP3663366A2_D0175.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.82; d 8.35; s 7.98; tr 7.77; tr 7.30; d 5.28; m 4.49-4.59; s 3.88; tr 2.35; m 1.62-1.71; m 1.20-1.41; m 0.85-0.93 [ppm]</entry><entry>0.3 µM</entry></row><row><entry>2-22</entry><entry><chemistry id="chem0176" num="0176"><img file="EP3663366A2_D0176.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): br s 10.58; s 8.81; d 8.35; s 7.97; tr 7.78; tr 7.31; d 5.29; m 4.49-4.59; s 3.90; tr 2.35; m 1.60-1.70; m 1.20-1.42; tr 0.88 [ppm]</entry><entry>0.7 µM</entry></row></tbody></tgroup></table></tables><tables id="tabl0071" num="0071"><table frame="all"><title>Table C:</title><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="12mm" /><colspec colnum="2" colname="col2" colwidth="62mm" /><colspec colnum="3" colname="col3" colwidth="78mm" /><colspec colnum="4" colname="col4" colwidth="15mm" /><thead><row><entry valign="top">No.</entry><entry valign="top">Structure type 3</entry><entry valign="top">Physics. Data</entry><entry valign="top">EC₅₀</entry></row></thead><tbody><row><entry>3-1</entry><entry><chemistry id="chem0177" num="0177"><img file="EP3663366A2_D0177.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.62; tr 7.80; d 7.57; 7.32-7.38; d 7.17; d 6.80; mm 6.65-6.72; s 5.91; d 5.80; m 4.62-4.71; d 1.96; d 1.75; d 1.60; m 1.34-1.46; m 1.22-1.34; m 0.93-1.06 [ppm]</entry><entry>0.1 µM</entry></row><row><entry>3-2</entry><entry><chemistry id="chem0178" num="0178"><img file="EP3663366A2_D0178.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.50; s 7.00; d 6.97; d 6.78; d 6.68; s 5.96; br s 3.56; m 1.06-2.48 [ppm]</entry><entry>11.8 µM</entry></row><row><entry>3-3</entry><entry><chemistry id="chem0179" num="0179"><img file="EP3663366A2_D0179.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.55; m 7.37-7.47; m 7.12-7.18; d 6.78; m 6.62-6.71; tr 4.72; d 1.88; d 1.74; d 1.58; q 1.43; q 1.11 [ppm]</entry><entry>0.9 µM</entry></row><row><entry>3-4</entry><entry><chemistry id="chem0180" num="0180"><img file="EP3663366A2_D0180.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m 7.53-7.68; m 6.96-7.08; d 6.79; m 6.60-6.76; s 5.96; br s 4.50; m 3.72-3.82; m 3.33-3.46; m 1.04-1.92 [ppm]</entry><entry>0.8 µM</entry></row><row><entry>3-5</entry><entry><chemistry id="chem0181" num="0181"><img file="EP3663366A2_D0181.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.51; s 7.03; d 6.97; d 6.80; d 6.67; s 5.98; m 3.33-4.17; br s 2.22; m 1.03-1.94 [ppm]</entry><entry>0.2 µM</entry></row><row><entry>3-6</entry><entry><chemistry id="chem0182" num="0182"><img file="EP3663366A2_D0182.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.68; m 7.16-7.48; d 6.90; s 6.78; d 6.75; d 6.30; s 5.95 [ppm]</entry><entry>0.8 µM</entry></row><row><entry>3-7</entry><entry><chemistry id="chem0183" num="0183"><img file="EP3663366A2_D0183.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.59; m 7.34-7.48; d 7.21; m 6.80-6.88; m 6.63-6.77; d 6.11; s 5.91; tr 3.80; m 1.54-1.66; tr 0.92 [ppm]</entry><entry>1.1 µM</entry></row><row><entry>3-8</entry><entry><chemistry id="chem0184" num="0184"><img file="EP3663366A2_D0184.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.56; m 7.39-7.50; m 7.12-7.20; d 6.80; d 6.70; s 6.66; m 5.86-5.97; m 5.06-5.19; d 1.12 [ppm]</entry><entry>0.6 µM</entry></row><row><entry>3-9</entry><entry><chemistry id="chem0185" num="0185"><img file="EP3663366A2_D0185.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.58; m 7.34-7.47; d 7.20; d 6.83; m 6.67-6.76; d 6.11; s 5.90; tr 3.83; m 1.50-1.60; m 1.30-1.40; tr 0.90 [ppm]</entry><entry>0.7 µM</entry></row><row><entry>3-10</entry><entry><chemistry id="chem0186" num="0186"><img file="EP3663366A2_D0186.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.65; m 7.18-7.36; d 7.06; d 6.84; m 6.67-6.74; d 6.16; s, 5.88; s 5.02 [ppm]</entry><entry>1.2 µM</entry></row><row><entry>3-11</entry><entry><chemistry id="chem0187" num="0187"><img file="EP3663366A2_D0187.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.54; tr 7.73; d 7.64; m 7.18-7.24; d 6.86; s 6.80; d 6.72; d 6.27; s 5.90; q 4.07; tr 1.22 [ppm]</entry><entry>6.2 µM</entry></row><row><entry>3-12</entry><entry><chemistry id="chem0188" num="0188"><img file="EP3663366A2_D0188.tif" /></chemistry></entry><entry>Retention time (HPLC): 8.99 min; Method 2 in the Appendix</entry><entry>0.7 µM</entry></row><row><entry>3-13</entry><entry><chemistry id="chem0189" num="0189"><img file="EP3663366A2_D0189.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m 7.61-7.74; m 6.94-7.39; m 6.65-6.94; d 6.48; m 5.81-6.00; m 4.89-5.03; m 4.31-4.72; m 1.06-1.28 [ppm]</entry><entry>3.9 µM</entry></row><row><entry>3-14</entry><entry><chemistry id="chem0190" num="0190"><img file="EP3663366A2_D0190.tif" /></chemistry></entry><entry>Retention time (HPLC): 8.93 min; Method 2 in the Appendix</entry><entry>1.5 µM</entry></row><row><entry>3-15</entry><entry><chemistry id="chem0191" num="0191"><img file="EP3663366A2_D0191.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.62; s 7.04; m 6.96-7.01; d 6.78; d 6.67; s 5.97; m 3.40-3.52; m 1.13-1.30</entry><entry>12.3 µM</entry></row><row><entry>3-16</entry><entry><chemistry id="chem0192" num="0192"><img file="EP3663366A2_D0192.tif" /></chemistry></entry><entry>Retention time (HPLC): 12.31 min; Method 2 in the Appendix</entry><entry>8.2 µM</entry></row><row><entry>3-17</entry><entry><chemistry id="chem0193" num="0193"><img file="EP3663366A2_D0193.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.62; tr 7.80; d 7.65; m 7.35-7.42; m 7.12-7.28; d 6.78; d 5.90; tr 4.69; s 3.72; d 1.98; d 1.75; d 1.59; m 1.24-1.50; m 0.92-1.06 [ppm]</entry><entry>0.4 µM</entry></row><row><entry>3-18</entry><entry><chemistry id="chem0194" num="0194"><img file="EP3663366A2_D0194.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.55; d 7.46; d 6.90; d 6.72; s 3.82; br s 3.59; br s 2.28; m 1.08-1.93 [ppm]</entry><entry>0.1 µM</entry></row><row><entry>3-19</entry><entry><chemistry id="chem0195" num="0195"><img file="EP3663366A2_D0195.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.61; s 7.40; m 7.10-7.20; d 6.76; d 5.95; m 4.68-4.78; s 3.72; d 1.90; d 1.74; d 1.58; q 1.43; q 1.11; q 0.92 [ppm]</entry><entry>0.7µM</entry></row><row><entry>3-20</entry><entry><chemistry id="chem0196" num="0196"><img file="EP3663366A2_D0196.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.74; m 7.15-7.39; d 6.79; d 6.36; s 3.81 [ppm]</entry><entry>1.1 µM</entry></row><row><entry>3-21</entry><entry><chemistry id="chem0197" num="0197"><img file="EP3663366A2_D0197.tif" /></chemistry></entry><entry>¹H-NMR: (CDCl₃) d 7.64; m 7.33-7.46; tr 7.21; d 6.76; d 6.18; d 3.80; s 3.72; m 1.55-1.66; tr 0.92 [ppm]</entry><entry>1.7 µM</entry></row><row><entry>3-22</entry><entry><chemistry id="chem0198" num="0198"><img file="EP3663366A2_D0198.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.61; m 7.38-7.46; m 7.12-7.22; d 6.76; d 5.97; m 5.08-5.18; s 3.74; d 1.12 [ppm]</entry><entry>1.3 µM</entry></row><row><entry>3-23</entry><entry><chemistry id="chem0199" num="0199"><img file="EP3663366A2_D0199.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.71; m 7.18-7.36; d 7.06; d 6.78; d 6.22; s 5.03; s 3.73</entry><entry>3.2 µM</entry></row><row><entry>3-24</entry><entry><chemistry id="chem0200" num="0200"><img file="EP3663366A2_D0200.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m 8.46-8.54; d 7.74; tr 7.60; m 7.02-7.32; d 6.80; d 6.38; s 5.27; s 3.73 [ppm]</entry><entry>2.2 µM</entry></row><row><entry>3-25</entry><entry><chemistry id="chem0201" num="0201"><img file="EP3663366A2_D0201.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m 8.60-8.66; m 7.75-7.83; d 7.67; m 7.31-7.39; s 7.25; d 7.16; d 6.0; m 4.64-4.73; d, 1.97; d 1.75; d 1.60; m 1.24-1.48; m 0.94-1.06 [ppm]</entry><entry>2.3 µM</entry></row><row><entry>3-26</entry><entry><chemistry id="chem0202" num="0202"><img file="EP3663366A2_D0202.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.64; m 7.38-7.49; m 7.20-7.30; m 7.12-7.20; d 6.06; m 4.67-4.78; d 1.90; d 1.75; d 1.60; m 1.38-1.50; m 1.07-1.18; 0.87-1.01 [ppm]</entry><entry>0.6 µM</entry></row><row><entry>3-27</entry><entry><chemistry id="chem0203" num="0203"><img file="EP3663366A2_D0203.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.78; m 7.21-7.47; d 6.49 [ppm]</entry><entry>2.9 µM</entry></row><row><entry>3-28</entry><entry><chemistry id="chem0204" num="0204"><img file="EP3663366A2_D0204.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.78; m 6.91-7.50; d 6.36; s 5.03 [ppm]</entry><entry>2.4 µM</entry></row><row><entry>3-29</entry><entry><chemistry id="chem0205" num="0205"><img file="EP3663366A2_D0205.tif" /></chemistry></entry><entry>Retention time (HPLC): 11.56 min; Method 2 in the Appendix</entry><entry>0.8 µM</entry></row><row><entry>3-30</entry><entry><chemistry id="chem0206" num="0206"><img file="EP3663366A2_D0206.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.62; d 7.96; tr 7.79; m 7.30-7.36; m 7.08-7.20; tr 7.04; d 5.90; m 4.64-4.72; s 2.36; d 1.98; d 1.76; d 1.60; q 1.42; q 1.30; m 0.95-1.06 [ppm]</entry><entry>0.4 µM</entry></row><row><entry>3-31</entry><entry><chemistry id="chem0207" num="0207"><img file="EP3663366A2_D0207.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.62; tr 7.78; d 7.64; m 7.32-7.36; m 7.10-7.19; m 7.02-7.10; d 5.96; m 4.62-4.71; s 2.28; d 1.97; d 1.77; d 1.61; q 1.42; q 1.29; m 0.95-1.06 [ppm]</entry><entry>0.3 µM</entry></row><row><entry>3-32</entry><entry><chemistry id="chem0208" num="0208"><img file="EP3663366A2_D0208.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.62; tr 7.78; d 7.64; m 7.31-7.37; m 7.11-7.19; d 7.06; d 5.94; m 4.62-4.72; s 2.28; d 1.96; d 1.76; d 1.60; m 1.35-1.48; m 1.23-1.35; m 0.93-1.06 [ppm]</entry><entry>0.3 µM</entry></row><row><entry>3-33</entry><entry><chemistry id="chem0209" num="0209"><img file="EP3663366A2_D0209.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.55; d 7.40; d 7.16; d 6.80; br s 3.57; s 2.36; br s 2.29; m 1.04-1.96 [ppm]</entry><entry>2.1 µM</entry></row><row><entry>3-34</entry><entry><chemistry id="chem0210" num="0210"><img file="EP3663366A2_D0210.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.76; m 7.12-7.42; d 7.07; d 6.44; s 2.29 [ppm]</entry><entry>4.0 µM</entry></row><row><entry>3-25</entry><entry><chemistry id="chem0211" num="0211"><img file="EP3663366A2_D0211.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.67; m 7.30-7.45; tr 7.20; d 7.06; d 6.34; s 3.40, s 2.28 [ppm]</entry><entry>4.2 µM</entry></row><row><entry>3-36</entry><entry><chemistry id="chem0212" num="0212"><img file="EP3663366A2_D0212.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.65; 7.38-7.49; m 7.09-7.20; d 7.03; d 6.06; m 5.07-5.19; s 2.26; d 1.13</entry><entry>1.8 µM</entry></row><row><entry>3-37</entry><entry><chemistry id="chem0213" num="0213"><img file="EP3663366A2_D0213.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.62; tr 7.78; d 7.64; m 7.31-7.36; m 7.13-7.19; m 6.76-6.88; d 5.98; m 4.63-4.72; s 3.71; d 1.96; d 1.76; d 1.59; q 1.41; q 1.29; m 0.94-1.06 [ppm]</entry><entry>3.0 µM</entry></row><row><entry>3-38</entry><entry><chemistry id="chem0214" num="0214"><img file="EP3663366A2_D0214.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.62; d 7.87; tr 7.80; tr 7.33; d 7.17; tr 6.92; d 6.83; d 6.77; d 6.15; m 4.62-4.72; s 3.82; s 3.69; d 1.98; d 1.77; d 1.61; q 1.42; q 1.30; m 0.95-1.07 [ppm]</entry><entry>0.7 µM</entry></row><row><entry>3-39</entry><entry><chemistry id="chem0215" num="0215"><img file="EP3663366A2_D0215.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 7.85; m 7.37-7.46; d 7.15; tr 6.90; d 6.80; d 6.74; d 6.25; m 4.68-4.78; s 3.80; s 3.66; d 1.91; d 1.76; d 1.60; q 1.44; q 1.14; m 0.89-1.00 [ppm]</entry><entry>2.6 µM</entry></row><row><entry>3-40</entry><entry><chemistry id="chem0216" num="0216"><img file="EP3663366A2_D0216.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 8.00; m 7.05-7.68; tr 6.94; m 6.70-6.90; d 6.64; s 3.82; s 3.73 [ppm]</entry><entry>5.9 µM</entry></row><row><entry>3-41</entry><entry><chemistry id="chem0217" num="0217"><img file="EP3663366A2_D0217.tif" /></chemistry></entry><entry>Retention time (HPLC): 10.43 min; Method 2 in the Appendix</entry><entry>0.7 µM</entry></row><row><entry>3-42</entry><entry><chemistry id="chem0218" num="0218"><img file="EP3663366A2_D0218.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): d 8.56; tr 7.70; m 7.24-7.30; d 6.96; d 6.90; d 6.76; m 4.50-4.60; s 3.73; tr 2.86; tr 2.18; d 1.90; d 1.72; 1.57; m 1.30-1.44; m 1.02-1.14; m 0.86-1.00 [ppm]</entry><entry>3.3 µM</entry></row><row><entry>3-43</entry><entry><chemistry id="chem0219" num="0219"><img file="EP3663366A2_D0219.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): m 7.00-7.43; d 6.69; m 6.55-6.60; s 5.87; tr 2.90; tr 2.52 [ppm]</entry><entry>6.8 µM</entry></row><row><entry>3-44</entry><entry><chemistry id="chem0220" num="0220"><img file="EP3663366A2_D0220.tif" /></chemistry></entry><entry>Retention time (HPLC): 10.96 min; Method 2 in the Appendix</entry><entry>1.0 µM</entry></row><row><entry>3-45</entry><entry><chemistry id="chem0221" num="0221"><img file="EP3663366A2_D0221.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.56; tr 7.78; mm 7.28-7.36; d 7.17; d 6.76; d 6.70; d 1.92; d 1.73; d 1.58; m 1.29-1.42; m 1.14-1.29; m 0.90-1.02 [ppm]</entry><entry>4.0µM</entry></row><row><entry>3-46</entry><entry><chemistry id="chem0222" num="0222"><img file="EP3663366A2_D0222.tif" /></chemistry></entry><entry>Retention time (HPLC): 9.86 min; Method 2 in the Appendix</entry><entry>3.0 µM</entry></row><row><entry>3-47</entry><entry><chemistry id="chem0223" num="0223"><img file="EP3663366A2_D0223.tif" /></chemistry></entry><entry>Retention time (HPLC): 11.63 min; Method 2 in the Appendix</entry><entry>1.7 µM</entry></row><row><entry>3-48</entry><entry><chemistry id="chem0224" num="0224"><img file="EP3663366A2_D0224.tif" /></chemistry></entry><entry>¹H-NMR (CDCl₃): s 8.47; tr 7.45; d 7.23; m 7.05-7.10; d 6.78; d 6.62; m 4.64-4.72; s 3.68; d 1.97; d 1.78; m 1.49-1.66; q 1.42; m 1.02-1.13 [ppm]</entry><entry>10.9 µM</entry></row><row><entry>3-49</entry><entry><chemistry id="chem0225" num="0225"><img file="EP3663366A2_D0225.tif" /></chemistry></entry><entry>Retention time (HPLC): 9.40 min; Method 2 in the Appendix</entry><entry>5.5 µM</entry></row></tbody></tgroup></table></tables><tables id="tabl0072" num="0072"><table frame="none"><title><b>HPLC method 1</b></title><tgroup cols="5" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="32mm" /><colspec colnum="2" colname="col2" colwidth="18mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="22mm" /><thead><row><entry valign="top"><b>Meth.</b></entry><entry namest="col2" nameend="col5" align="left" valign="top"><b>CBMPPA-A</b></entry></row></thead><tbody><row><entry>Pillar:</entry><entry namest="col2" nameend="col5" align="left">Luna C8 (2), 150 * 3.0mm (Phenomenex)</entry></row><row><entry>Guard column:</entry><entry namest="col2" nameend="col5" align="left">C18 ODS</entry></row><row><entry>Temperature:</entry><entry namest="col2" nameend="col5" align="left">40 ° C</entry></row><row><entry>Flow rate:</entry><entry namest="col2" nameend="col5" align="left">1.00 ml / min</entry></row><row><entry>Injection volume:</entry><entry namest="col2" nameend="col5" align="left">1.0 µl</entry></row><row><entry>Detection:</entry><entry namest="col2" nameend="col5" align="left">UV 264nm</entry></row><row><entry>Stop time:</entry><entry namest="col2" nameend="col5" align="left">4.0 minutes</entry></row><row><entry>Follow-up time:</entry><entry namest="col2" nameend="col5" align="left">0.0 minutes</entry></row><row><entry>Maximum pressure:</entry><entry namest="col2" nameend="col5" align="left">300 bar</entry></row><row><entry>Eluent A:</entry><entry namest="col2" nameend="col5" align="left">10mM KH2PO4, pH2.5</entry></row><row><entry>Eluent B:</entry><entry namest="col2" nameend="col5" align="left">Acetonitrile</entry></row><row><entry>Gradient:</entry><entry align="center">Time [min]</entry><entry align="center">A [%]</entry><entry align="center">B [%]</entry><entry align="center">Flow [ml / min]</entry></row><row><entry /><entry align="center">0,0</entry><entry align="center">75,0</entry><entry align="center">25,0</entry><entry align="center">1,00</entry></row><row><entry /><entry align="center">4,0</entry><entry align="center">75,0</entry><entry align="center">25,0</entry><entry align="center">1,00</entry></row><row><entry>Matrix:</entry><entry namest="col2" nameend="col5" align="left">Sample is filtered through 0.22 µm.</entry></row><row><entry>Calibration:</entry><entry namest="col2" nameend="col5" align="left">with standard 10mmol / L in DMSO</entry></row></tbody></tgroup></table></tables><tables id="tabl0073" num="0073"><table frame="none"><title><b>HPLC method 2</b></title><tgroup cols="5" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="32mm" /><colspec colnum="2" colname="col2" colwidth="18mm" /><colspec colnum="3" colname="col3" colwidth="14mm" /><colspec colnum="4" colname="col4" colwidth="14mm" /><colspec colnum="5" colname="col5" colwidth="22mm" /><thead><row><entry valign="top"><b>Meth.</b></entry><entry namest="col2" nameend="col5" align="left" valign="top"><b>TRPM8-A</b></entry></row></thead><tbody><row><entry>Pillar:</entry><entry namest="col2" nameend="col5" align="left">Luna C8 (2), 150 * 3.0mm (Phenomenex)</entry></row><row><entry>Guard column:</entry><entry namest="col2" nameend="col5" align="left">C18 ODS</entry></row><row><entry>Temperature:</entry><entry namest="col2" nameend="col5" align="left">40 ° C</entry></row><row><entry>Flow rate:</entry><entry namest="col2" nameend="col5" align="left">1.00 ml / min</entry></row><row><entry>Injection volume:</entry><entry namest="col2" nameend="col5" align="left">1.0 µl</entry></row><row><entry>Detection:</entry><entry namest="col2" nameend="col5" align="left">UV 210nm</entry></row><row><entry>Stop time:</entry><entry namest="col2" nameend="col5" align="left">17.0 minutes</entry></row><row><entry>Follow-up time:</entry><entry namest="col2" nameend="col5" align="left">3.0 minutes</entry></row><row><entry>Maximum pressure:</entry><entry namest="col2" nameend="col5" align="left">300 bar</entry></row><row><entry>Eluent A:</entry><entry namest="col2" nameend="col5" align="left">10mM KH2PO4, pH2.5</entry></row><row><entry>Eluent B:</entry><entry namest="col2" nameend="col5" align="left">Acetonitrile</entry></row><row><entry>Gradient:</entry><entry align="center">Time [min]</entry><entry align="center">A [%]</entry><entry align="center">B [%]</entry><entry align="center">Flow [ml / min]</entry></row><row><entry /><entry align="center">0,0</entry><entry align="center">95,0</entry><entry align="center">5,0</entry><entry align="center">1,00</entry></row><row><entry /><entry align="center">17,0</entry><entry align="center">40,0</entry><entry align="center">60,0</entry><entry align="center">1,00</entry></row><row><entry>Matrix:</entry><entry namest="col2" nameend="col5" align="left">Sample is filtered through 0.22 µm.</entry></row></tbody></tgroup></table></tables>

0534Reference is hereby expressly made to the disclosure of the literature references cited herein.

Test example 2

0535Evaluation of the time course of the cooling intensities of the compounds to be used according to the invention.

0536Process: The cooling substances to be used according to the invention were incorporated into toothpaste according to Table Z (see below).

0537The sensory properties of the resulting toothpaste were evaluated by a trained panel (of 6 people). For this purpose, the teeth were first brushed with the toothpaste containing the compounds according to the invention for 30 seconds, then the toothpaste foam was spat out and the mouth was rinsed once with water. The test subjects rated the strength of the feeling of cold on a scale from 0 (no feeling of cold) to 9 (extremely strong feeling of cold). The feeling of coldness was assessed after 30 sec, 1, 5, 10, 20, 30, 45 and 60 min.

0538The compounds according to the invention from structure classes 1, 2 and 3 were the compounds <i>2,3,4,5,6,10b, 11,12-octahydro-spiro [4b-azachrysen-12,2 '- [1,3] dithiolan -] - 1-one</i> ((<b>LN <u>1</u></b>)); <i>Isopropyl- (5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl) amine</i> ((<b>LN <u>9</u></b>)) and <i>3,4-methylenedioxycinnamic acid-N, N-diphenylamide</i> ((<b>LN 24</b>)) tested.

0539For comparison, toothpastes with the same composition were tested, which as a conventional cooling substance menthan-3-carboxylic acid-N-ethylamide ("WS 3", see <patcit id="pcit0085" dnum="US4150052A"><text>US 4,150,052</text></patcit>) contained.

0540The result is in <figref idref="f0004">Figure 3</figref> shown and shows that the cooling substances according to the invention are clearly superior to the conventionally used both in terms of a quickly perceptible intensity and in terms of the duration of the cooling perception (the <figref idref="f0001 f0002">Figure 1</figref> represents how perceived cooling intensities of the respective cooling substance when used in a flavored toothpaste at a dosage of 100 ppm based on the entire toothpaste). Thus, the cooling substances according to the invention convey a very clearly perceptible feeling of cold even 1 hour after brushing the teeth, whereas after this time it has completely disappeared in the case of the conventional comparison compound.<tables id="tabl0074" num="0074"><table frame="all"><title>Table Z</title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="54mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><colspec colnum="3" colname="col3" colwidth="11mm" /><tbody><row><entry><b>Deionized water</b></entry><entry><b>27,52</b></entry><entry /></row><row><entry><b>Sorbitol 700/0</b></entry><entry><b>45</b></entry><entry /></row><row><entry><b>Solbrol M Na salt</b></entry><entry><b>0.15</b></entry><entry /></row><row><entry><b>Trisodium phosphate</b></entry><entry><b>0,1</b></entry><entry /></row><row><entry><b>Saccharin</b></entry><entry><b>0.2</b></entry><entry /></row><row><entry><b>Sodium monofluorophosphate</b></entry><entry><b>1.12</b></entry><entry /></row><row><entry><b>PEG 1500</b></entry><entry>5</entry><entry /></row><row><entry><b>Sident 9 (abrasive silica)</b></entry><entry><b>10</b></entry><entry /></row><row><entry><b>Sident 22 S (Thickening Silica)</b></entry><entry>8</entry><entry /></row><row><entry><b>Sodium carboxymethyl cellulose</b></entry><entry><b>0.9</b></entry><entry /></row><row><entry><b>Titanium (IV) oxide</b></entry><entry><b>0.5</b></entry><entry /></row><row><entry><b>Sodium Lauryl Sulfate (SLS)</b></entry><entry><b>1,5</b></entry><entry /></row><row><entry><b>respective cooling substance</b></entry><entry><b>0,01</b></entry><entry /></row><row><entry /><entry /><entry /></row><row><entry><b>Total</b></entry><entry /><entry><b>100</b></entry></row></tbody></tgroup></table></tables>

All figures in% by weight

Embodiment 1:

0541Method for in-vitro or in-vivo modulation of the cold menthol receptor TRPM8, wherein the receptor is brought into contact with at least one modulator which is selected from compounds of the following structure types 1 to 3:<ol id="ol0009" compact="compact"><li>a) Structure type 1:<chemistry id="chem0226" num="0226"><img file="EP3663366A2_D0226.tif" /></chemistry>wherein<ul id="ul0026" list-style="none"><li>R₁₁, R₁₂ and R₁₃ are independently selected from:<ul id="ul0027" list-style="none"><li>H; straight-chain or branched C₁-C₆-Alkylgruppen, which optionally carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆Alkoxy groups; and</li><li>straight-chain or branched C₁-C₆-Alkyloxy groups, which may carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or</li><li>R₁₁ and R₁₂ together with the carbon atoms to which they are attached form a 4-, 5-, 6- or 7-membered, mono- or polyunsaturated, carbo- or heterocyclic ring which may be 1, 2, 3, 4 or 5 identical or carries various substituents which are selected from straight-chain or branched C₁-C₆-Alkyl groups, and oxo groups (= O), and the ring heteroatoms are the same or different and are selected from O, N and S;</li></ul></li><li>X and Z are independently selected from -O-, -S-, -NH-, -S (= O) -, or -S (= O)₂- Groups; and</li><li>Y is selected under straight-chain or branched C₁-C₈Alkylene groups, which may carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or</li><li>XYZ together with the carbon atom to which they are attached form a keto group</li><li>and salts of these compounds, in particular acid addition salts with inorganic or in particular organic, mono- or in particular polyvalent carboxylic acids;</li><li>and optionally in stereoisomerically pure form or as a mixture of stereoisomers;</li></ul></li><li>b) Structure type 2:<chemistry id="chem0227" num="0227"><img file="EP3663366A2_D0227.tif" /></chemistry>wherein<ul id="ul0028" list-style="none"><li>R₂₁ and R₂₂ are independently selected from:<ul id="ul0029" list-style="none"><li>H;</li><li>straight-chain or branched C₁-C₆-Alkylgruppen, which optionally carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>straight-chain or branched C₁-C₆-Alkyloxy groups, which may carry 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>mononuclear or polynuclear aryl, arylalkyl and heteroaryl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S;</li></ul></li><li>R23 is selected from:<ul id="ul0030" list-style="none"><li>H;</li><li>straight-chain or branched C₁-C₆-Alkyl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>C.₃-C₇-Cycloalkyl groups, which may carry 1,2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups, or straight-chain or branched C₁-C₆-Alkoxy groups; where the cycloalkyl group optionally via a C₁-C₄-Alkylene group is bonded to Z; and where optionally 1, 2 or 3 ring carbon atoms can be replaced by identical or different heteroatoms selected from O, N and S;</li><li>mononuclear or polynuclear aryl, arylalkyl and heteroaryl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S;</li><li>X is selected from O, S or methylene;</li></ul></li><li>Y is selected from N or CH; and</li><li>Z is selected from O, S or NR₂₄, in which<ul id="ul0031" list-style="none"><li>R₂₄ for H; or a straight-chain or branched C₁-C₆-Alkylgruppe, which optionally carries 1, 2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups; or</li><li>R₂₄ and R₂₃ together with the Z group to which they are attached form a 4-, 5-, 6- or 7-membered, saturated or mono- or polyunsaturated heterocyclic ring which may be 1, 2, 3, 4 or 5 carries the same or different substituents, which are selected from straight-chain or branched C₁-C₆Alkyl groups, and which has 1, 2 or 3 additional ring heteroatoms which are the same or different and are selected from O, N and S;</li></ul></li><li>and salts of these compounds, in particular acid addition salts with inorganic or in particular organic, mono- or in particular polyvalent carboxylic acids;</li><li>and optionally in stereoisomerically pure form or as a mixture of stereoisomers; and</li></ul></li><li>c) Structure type 3:<chemistry id="chem0228" num="0228"><img file="EP3663366A2_D0228.tif" /></chemistry>wherein<ul id="ul0032" list-style="none"><li>R₃₁, R₃₂, R₃₃, R₃₄ and R₃₅ are the same or different and are selected from<ul id="ul0033" list-style="none"><li>H;</li><li>Halogen;</li><li>straight-chain or branched C₁-C₆-Alkyl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>straight-chain or branched C₁-C₆Alkoxy groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or C₁-C₆-Alkoxy groups;</li><li>mononuclear or polynuclear aryl, arylalkyl and heteroaryl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkyloxy groups; wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S; or</li><li>two adjacent residues R₃₁, R₃₂, R₃₃, R₃₄ and R₃₅ together with the carbon atoms to which they are attached form a 4-, 5-, 6- or 7-membered, mono- or polyunsaturated heterocyclic ring which may have 1, 2, 3, 4 or 5 identical or different substituents , which are selected from straight-chain or branched C₁-C₆Alkyl groups, and which has 1, 2 or 3 ring heteroatoms which are the same or different and are selected from O, N and S;</li></ul></li><li>R₃₆ and R₃₇ are the same or different and are selected from:<ul id="ul0034" list-style="none"><li>straight-chain or branched C₁-C₆-Alkyl groups which may carry 1, 2, 3 or 4 identical or different substituents which are selected from NH₂, OH, SH, halogen or straight-chain or branched C₁-C₆-Alkoxy groups;</li><li>mononuclear or polynuclear aryl, arylalkyl, aryloxy, heteroaryl and heteroaryloxy groups, which may have 1, 2, 3 or 4 identical or different substituents selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups and straight-chain or branched C₁-C₆-Alkoxy groups; wherein the heteroaryl groups have 1, 2, 3 or 4 ring heteroatoms which are the same or different and are selected from O, N and S;</li><li>and C₃-C₇-Cycloalkyl groups, which may carry 1,2, 3 or 4 identical or different substituents, which are selected from NH₂, OH, SH, halogen, straight-chain or branched C₁-C₆-Alkyl groups, or straight-chain or branched C₁-C₆-Alkoxy groups; where the cycloalkyl group optionally via a C₁-C₄-Alkylene group is bound; and where optionally 1, 2 or 3 ring carbon atoms can be replaced by identical or different heteroatoms selected from O, N and S;</li></ul></li><li>X is selected under -C₁-C₄Alkylene groups; -C₂-C₄-Alkenylene groups, and -ZC₁-C₄- or -C₁-C₄-Z- alkylene groups or -ZC₂-C₄- or - C₂-C₄-Z-alkenylene groups, where Z is O, S or NH; or represents a chemical single bond;</li><li>and salts of these compounds, in particular acid addition salts with inorganic or in particular organic, mono- or in particular polyvalent carboxylic acids;</li><li>and optionally in stereoisomerically pure form or as a mixture of stereoisomers.</li></ul></li></ol>

Embodiment 2:

0542The method of embodiment 1, wherein the receptor is brought into contact with at least one compound which, in a cellular activity test using cells which recombinantly express the human TRPM8 receptor, determines the permeability of these cells for Ca²⁺ Modulate ions.

Embodiment 3:

0543The method of embodiment 1, wherein the modulating compound acts on the cellular Ca2 + ion permeability agonistically or antagonistically.

Embodiment 4:

0544A method according to any one of embodiments 1 to 3, the modulating compound is a TRPM8 receptor agonist.

Embodiment 5:

0545Use of a compound as defined in one of the embodiments 1 to 4 for inducing a feeling of cold in humans and / or animals.

Embodiment 6:

0546Use of a compound as defined in any one of embodiments 1 to 4 as an active ingredient of a pharmaceutical agent.

Embodiment 7:

0547Use of a compound as defined in one of embodiments 1 to 4, for the treatment of prostate cancer, for the treatment of bladder weakness or in pain therapy.

Embodiment 8:

0548Use of a compound as defined in one of the embodiments 1 to 4 for inducing a feeling of coldness through a package.

Embodiment 9:

0549Use of a compound as defined in one of the embodiments 1 to 4 for inducing a feeling of cold through a textile.

Embodiment 10:

0550Use according to embodiment 5, wherein an agent is used, comprising at least one, two, three or more of the compounds according to the definitions from one of embodiments 1 to 4 and selected from group A consisting of<tables id="tabl0075" num="0075"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="56mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">1</entry><entry valign="middle"><chemistry id="chem0229" num="0229"><img file="EP3663366A2_D0229.tif" /></chemistry></entry></row><row><entry valign="middle">2</entry><entry valign="middle"><chemistry id="chem0230" num="0230"><img file="EP3663366A2_D0230.tif" /></chemistry></entry></row><row><entry valign="middle">3</entry><entry valign="middle"><chemistry id="chem0231" num="0231"><img file="EP3663366A2_D0231.tif" /></chemistry></entry></row><row><entry valign="middle">4</entry><entry valign="middle"><chemistry id="chem0232" num="0232"><img file="EP3663366A2_D0232.tif" /></chemistry></entry></row><row><entry valign="middle">5</entry><entry valign="middle"><chemistry id="chem0233" num="0233"><img file="EP3663366A2_D0233.tif" /></chemistry></entry></row><row><entry valign="middle">6</entry><entry valign="middle"><chemistry id="chem0234" num="0234"><img file="EP3663366A2_D0234.tif" /></chemistry></entry></row><row><entry valign="middle">7</entry><entry valign="middle"><chemistry id="chem0235" num="0235"><img file="EP3663366A2_D0235.tif" /></chemistry></entry></row><row><entry valign="middle">8</entry><entry valign="middle"><chemistry id="chem0236" num="0236"><img file="EP3663366A2_D0236.tif" /></chemistry></entry></row><row><entry valign="middle">9</entry><entry valign="middle"><chemistry id="chem0237" num="0237"><img file="EP3663366A2_D0237.tif" /></chemistry></entry></row><row><entry valign="middle">10</entry><entry valign="middle"><chemistry id="chem0238" num="0238"><img file="EP3663366A2_D0238.tif" /></chemistry></entry></row><row><entry valign="middle">11</entry><entry valign="middle"><chemistry id="chem0239" num="0239"><img file="EP3663366A2_D0239.tif" /></chemistry></entry></row><row><entry valign="middle">12</entry><entry valign="middle"><chemistry id="chem0240" num="0240"><img file="EP3663366A2_D0240.tif" /></chemistry></entry></row><row><entry valign="middle">13</entry><entry valign="middle"><chemistry id="chem0241" num="0241"><img file="EP3663366A2_D0241.tif" /></chemistry></entry></row><row><entry valign="middle">14</entry><entry valign="middle"><chemistry id="chem0242" num="0242"><img file="EP3663366A2_D0242.tif" /></chemistry></entry></row><row><entry valign="middle">15</entry><entry valign="middle"><chemistry id="chem0243" num="0243"><img file="EP3663366A2_D0243.tif" /></chemistry></entry></row><row><entry valign="middle">16</entry><entry valign="middle"><chemistry id="chem0244" num="0244"><img file="EP3663366A2_D0244.tif" /></chemistry></entry></row><row><entry valign="middle">17</entry><entry valign="middle"><chemistry id="chem0245" num="0245"><img file="EP3663366A2_D0245.tif" /></chemistry></entry></row><row><entry valign="middle">18</entry><entry valign="middle"><chemistry id="chem0246" num="0246"><img file="EP3663366A2_D0246.tif" /></chemistry></entry></row><row><entry valign="middle">19</entry><entry valign="middle"><chemistry id="chem0247" num="0247"><img file="EP3663366A2_D0247.tif" /></chemistry></entry></row><row><entry valign="middle">20</entry><entry valign="middle"><chemistry id="chem0248" num="0248"><img file="EP3663366A2_D0248.tif" /></chemistry></entry></row><row><entry valign="middle">21</entry><entry valign="middle"><chemistry id="chem0249" num="0249"><img file="EP3663366A2_D0249.tif" /></chemistry></entry></row><row><entry valign="middle">22</entry><entry valign="middle"><chemistry id="chem0250" num="0250"><img file="EP3663366A2_D0250.tif" /></chemistry></entry></row><row><entry valign="middle">23</entry><entry valign="middle"><chemistry id="chem0251" num="0251"><img file="EP3663366A2_D0251.tif" /></chemistry></entry></row><row><entry valign="middle">24</entry><entry valign="middle"><chemistry id="chem0252" num="0252"><img file="EP3663366A2_D0252.tif" /></chemistry></entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">25</entry><entry valign="middle"><chemistry id="chem0253" num="0253"><img file="EP3663366A2_D0253.tif" /></chemistry></entry></row><row><entry valign="middle">with R = H</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">26</entry><entry valign="middle"><chemistry id="chem0254" num="0254"><img file="EP3663366A2_D0254.tif" /></chemistry></entry></row><row><entry valign="middle">with R = Me</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">27</entry><entry valign="middle"><chemistry id="chem0255" num="0255"><img file="EP3663366A2_D0255.tif" /></chemistry></entry></row><row><entry valign="middle">with R = MeO</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">28</entry><entry valign="middle"><chemistry id="chem0256" num="0256"><img file="EP3663366A2_D0256.tif" /></chemistry></entry></row><row><entry valign="middle">with R = H</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">29</entry><entry valign="middle"><chemistry id="chem0257" num="0257"><img file="EP3663366A2_D0257.tif" /></chemistry></entry></row><row><entry valign="middle">with R = Me</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">30</entry><entry valign="middle"><chemistry id="chem0258" num="0258"><img file="EP3663366A2_D0258.tif" /></chemistry></entry></row><row><entry valign="middle">with R = MeO</entry></row></tbody></tgroup></table></tables>in a concentration of 0.1 ppm to 10% by weight based on the total weight of the agent for achieving a cooling effect on the skin or mucous membrane, which is compared with the cooling effect of an agent of the same composition, in which only the compound or compounds selected from the group A are replaced by menthane carboxylic acid-N-ethylamide in the same concentration, extended by at least 10 minutes, for non-therapeutic purposes.

Embodiment 11:

0551A substance as defined in any one of embodiments 1 to 4 for use as a mediator of the TRPM8 receptor.

Embodiment 12:

0552Agent containing at least one compound according to one of the embodiments 1 to 4.

Embodiment 13:

0553Means according to embodiment 12, selected from<ol id="ol0010"><li>a) pharmaceutical agents, such as anti-tumor agents, agents for the treatment of diseases of the bladder, pain relievers;</li><li>b) foods, such as ice cream, mousse, cream, beverages, confectionery,</li><li>c) oral care products such as toothpaste, mouthwash, chewing gum,</li><li>d) personal care products, such as skin or hair care products, such as sunscreen, sunburn cream, lotions, shampoos, plasters,</li><li>e) foaming and gelling.</li></ol>

Embodiment 14:

0554Agents according to embodiment 12 or 13 selected from the group consisting of aroma mixture and nutrition, oral hygiene or pleasure serving pharmaceutical or cosmetic preparation, comprising a two, three or more of the compounds according to the definitions from one of embodiments 1-4 and (i ) selected from group B consisting of<tables id="tabl0076" num="0076"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="56mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">1</entry><entry valign="middle"><chemistry id="chem0259" num="0259"><img file="EP3663366A2_D0259.tif" /></chemistry></entry></row><row><entry valign="middle">3</entry><entry valign="middle"><chemistry id="chem0260" num="0260"><img file="EP3663366A2_D0260.tif" /></chemistry></entry></row><row><entry valign="middle">4</entry><entry valign="middle"><chemistry id="chem0261" num="0261"><img file="EP3663366A2_D0261.tif" /></chemistry></entry></row><row><entry valign="middle">6</entry><entry valign="middle"><chemistry id="chem0262" num="0262"><img file="EP3663366A2_D0262.tif" /></chemistry></entry></row><row><entry valign="middle">7</entry><entry valign="middle"><chemistry id="chem0263" num="0263"><img file="EP3663366A2_D0263.tif" /></chemistry></entry></row><row><entry valign="middle">8</entry><entry valign="middle"><chemistry id="chem0264" num="0264"><img file="EP3663366A2_D0264.tif" /></chemistry></entry></row><row><entry valign="middle">10</entry><entry valign="middle"><chemistry id="chem0265" num="0265"><img file="EP3663366A2_D0265.tif" /></chemistry></entry></row><row><entry valign="middle">11</entry><entry valign="middle"><chemistry id="chem0266" num="0266"><img file="EP3663366A2_D0266.tif" /></chemistry></entry></row><row><entry valign="middle">12</entry><entry valign="middle"><chemistry id="chem0267" num="0267"><img file="EP3663366A2_D0267.tif" /></chemistry></entry></row><row><entry valign="middle">13</entry><entry valign="middle"><chemistry id="chem0268" num="0268"><img file="EP3663366A2_D0268.tif" /></chemistry></entry></row><row><entry valign="middle">14</entry><entry valign="middle"><chemistry id="chem0269" num="0269"><img file="EP3663366A2_D0269.tif" /></chemistry></entry></row><row><entry valign="middle">15</entry><entry valign="middle"><chemistry id="chem0270" num="0270"><img file="EP3663366A2_D0270.tif" /></chemistry></entry></row><row><entry valign="middle">16</entry><entry valign="middle"><chemistry id="chem0271" num="0271"><img file="EP3663366A2_D0271.tif" /></chemistry></entry></row><row><entry valign="middle">17</entry><entry valign="middle"><chemistry id="chem0272" num="0272"><img file="EP3663366A2_D0272.tif" /></chemistry></entry></row><row><entry valign="middle">18</entry><entry valign="middle"><chemistry id="chem0273" num="0273"><img file="EP3663366A2_D0273.tif" /></chemistry></entry></row><row><entry valign="middle">19</entry><entry valign="middle"><chemistry id="chem0274" num="0274"><img file="EP3663366A2_D0274.tif" /></chemistry></entry></row><row><entry valign="middle">20</entry><entry valign="middle"><chemistry id="chem0275" num="0275"><img file="EP3663366A2_D0275.tif" /></chemistry></entry></row><row><entry valign="middle">21</entry><entry valign="middle"><chemistry id="chem0276" num="0276"><img file="EP3663366A2_D0276.tif" /></chemistry></entry></row><row><entry valign="middle">22</entry><entry valign="middle"><chemistry id="chem0277" num="0277"><img file="EP3663366A2_D0277.tif" /></chemistry></entry></row><row><entry valign="middle">24</entry><entry valign="middle"><chemistry id="chem0278" num="0278"><img file="EP3663366A2_D0278.tif" /></chemistry></entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">25</entry><entry valign="middle"><chemistry id="chem0279" num="0279"><img file="EP3663366A2_D0279.tif" /></chemistry></entry></row><row><entry valign="middle">with R = H</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">26</entry><entry valign="middle"><chemistry id="chem0280" num="0280"><img file="EP3663366A2_D0280.tif" /></chemistry></entry></row><row><entry valign="middle">with R = Me</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">27</entry><entry valign="middle"><chemistry id="chem0281" num="0281"><img file="EP3663366A2_D0281.tif" /></chemistry></entry></row><row><entry valign="middle">with R = MeO</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">28</entry><entry valign="middle"><chemistry id="chem0282" num="0282"><img file="EP3663366A2_D0282.tif" /></chemistry></entry></row><row><entry valign="middle">with R = H</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">29</entry><entry valign="middle"><chemistry id="chem0283" num="0283"><img file="EP3663366A2_D0283.tif" /></chemistry></entry></row><row><entry valign="middle">with R = Me</entry></row><row rowsep="0"><entry morerows="1" rowsep="1" valign="middle">30</entry><entry valign="middle"><chemistry id="chem0284" num="0284"><img file="EP3663366A2_D0284.tif" /></chemistry></entry></row><row><entry valign="middle">with R = MeO</entry></row></tbody></tgroup></table></tables>and / or (ii) selected from group C consisting of<tables id="tabl0077" num="0077"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="10mm" /><colspec colnum="2" colname="col2" colwidth="50mm" /><thead><row><entry valign="middle">LN</entry><entry valign="middle">structure</entry></row></thead><tbody><row><entry valign="middle">2</entry><entry valign="middle"><chemistry id="chem0285" num="0285"><img file="EP3663366A2_D0285.tif" /></chemistry></entry></row><row><entry valign="middle">5</entry><entry valign="middle"><chemistry id="chem0286" num="0286"><img file="EP3663366A2_D0286.tif" /></chemistry></entry></row><row><entry valign="middle">9</entry><entry valign="middle"><chemistry id="chem0287" num="0287"><img file="EP3663366A2_D0287.tif" /></chemistry></entry></row><row><entry valign="middle">23</entry><entry valign="middle"><chemistry id="chem0288" num="0288"><img file="EP3663366A2_D0288.tif" /></chemistry></entry></row></tbody></tgroup></table></tables>wherein the compound or the compounds of group C is contained in a concentration of 0.05 to &lt;0.1 ppm or 0.1 ppm to 10% by weight, based on the total weight of the preparation, with the proviso that in the case (ii ) the preparation does not contain a mouthwash with the composition of 1 liter each<tables id="tabl0078" num="0078"><table frame="none"><tgroup cols="2" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="96mm" /><colspec colnum="2" colname="col2" colwidth="15mm" /><tbody><row><entry>Ethanol 95%</entry><entry>177mL</entry></row><row><entry>Sorbitol 70%</entry><entry>250 G</entry></row><row><entry>Compound of formula 2, 5, 9 or 23 as a 1% solution in ethanol</entry><entry>50mL</entry></row><row><entry>Peppermint oil,</entry><entry>0.30 g</entry></row><row><entry>Methyl salicylate</entry><entry>0.64 g</entry></row><row><entry>Eucalyptol</entry><entry>0.922 g</entry></row><row><entry valign="bottom">Thymol</entry><entry valign="bottom">0.639 g</entry></row><row><entry valign="bottom">Benzoic acid</entry><entry valign="bottom">1.50 g</entry></row><row><entry valign="bottom">Pluronic ® F127 non-ionic surfactant</entry><entry valign="bottom">5.00 g</entry></row><row><entry valign="bottom">Sodium saccharin</entry><entry valign="bottom">0.60 g</entry></row><row><entry valign="bottom">Sodium citrate</entry><entry valign="bottom">0.30 g</entry></row><row><entry valign="bottom">citric acid</entry><entry valign="bottom">0.10 g</entry></row><row><entry valign="bottom">Water qs</entry><entry valign="bottom">1 liter</entry></row></tbody></tgroup></table></tables>is.

Embodiment 15:

0555Composition according to embodiment 14 comprising<ul id="ul0035" list-style="none" compact="compact"><li>(1) one or more further substances with a physiological cooling effect, the further substance or one, several or all of the further substances (i) causing a taste effect or (ii) causing no taste effect, and or</li><li>(2) one or more flavorings without a physiological cooling effect and or</li><li>(3) one or more trigeminal or mouthwashing substances without a physiological cooling effect and or</li><li>(4) (iii) one or (iv) several compounds which, in the case of (iv) independently of one another or together, additionally cause a taste-modulating effect and / or a trigeminal and / or mouth-irritating stimulus.</li></ul>

Embodiment 16:

0556Product containing at least one compound as defined in one of the embodiments 1 to 4 selected from<ol id="ol0011"><li>a) textile products,</li><li>b) packaging materials,</li><li>c) tobacco products;</li><li>d) remedies;</li><li>e) hygiene products, or</li><li>f) refreshing towels.</li></ol>

Embodiment 17:

0557Substance as defined in one of the embodiments 1 to 4, selected from compounds of structure type 1, 2 or 3

Embodiment 18:

0558Fabric according to embodiment 17, selected from the compounds of the formulas 1-1 to 1-9, 2-1 to 2-22 and 3-1 to 3-49 listed in Tables A, B and C and the compounds of the listed in Table N Formula LN 7,8 and 20-22, optionally in stereoisomerically pure form, as a mixture of stereoisomers, and salts of these compounds.

Embodiment 19:

0559Method according to one of the embodiments 1 to 4 for achieving a physiological cooling effect on the skin and / or a mucous membrane which is compared with the cooling effect of an agent of the same composition, in which only the compound or the compounds selected from group A against menthane carboxylic acid N- are exchanged in the same concentration, extended by at least 10 minutes, with the following step:<ul id="ul0036" list-style="dash" compact="compact"><li>Applying a sufficient amount to achieve a physiological cooling effect of an agent according to one of the embodiments 2 to 9 to the skin and / or a mucous membrane, the method being non-therapeutic.</li></ul>

Embodiment 20:

0560Agent according to one of the embodiments 14 or 15 for preventing, combating or relieving symptoms of cough, runny nose, inflammation, sore throat or hoarseness symptoms.<img file="EP3663366A2_D0289.tif" /><img file="EP3663366A2_D0290.tif" /><img file="EP3663366A2_D0291.tif" /><img file="EP3663366A2_D0292.tif" /><img file="EP3663366A2_D0293.tif" />