Compositions having a physiological cooling effect
Abstract
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Term
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6 claims: 6 independent, 0 dependent
- 1CLAIMS:PATENTANSPRÜCHE: 1. Use of carboxamides of one of the formulas 1. Verwendung von Carboxamiden einer der Formeln R. R. R d R d -σι -σι E. E. • CONR, Rc 4 Or wherein R and R are each hydrogen atoms or alkyl groups of 1 to 5 carbon atoms or hydroxyalkyl groups of 1 to 8 carbon atoms and together contain not more than 8 carbon atoms and, if R4 is a hydrogen atom, RG may also be an alkylcarboxyalkyl group having up to 6 carbon atoms, or R4 and RG taken together represent an alkylene group having up to 6 carbon atoms, the ends of which are attached to the amide nitrogen atom and thus form a nitrogen heterocycle whose carbon atom chain may optionally be interrupted by oxygen, Rp R1, Rn, Rin and r IV each represents hydrogen atoms or alkyl groups having 1 to 5 carbon atoms, and R2 and R3 each represents alkyl groups with Ibis 5 carbon atoms, where • CONR,Rc 4 5 oder worin R und R jeweils Wasserstoffatome oder Alkylgruppen mit 1 bis 5 Kohlenstoffatomen oder Hydroxyalkylgruppen mit 1 bis 8 Kohlenstoffatomen bedeuten und zusammen nicht mehr als 8 Kohlenstoffatome ent10 halten und, wenn R4 ein Wasserstoffatom ist, Rg auch eine Alkylcarboxyalkylgruppe mit bis zu 6 Kohlenstoffatomen sein kann, oder R4 und Rg zusammengenommen eine Alkylengruppe mit bis zu 6 Kohlenstoffatomen bedeuten, deren Enden an das Amidstickstoffatom gebunden sind und so einen Stickstoffheterozyklus bilden, dessen Kohlenstoffatomkette gegebenenfalls durch Sauerstoff unterbrochen sein kann, Rp R1, Rn, Rin und rIV jeweils Wasserstoffatome oder Alkylgruppen mit 1 bis 5 Kohlenstoffatomen bedeuten und R2 und R3 je15 weils Alkylgruppen mit Ibis 5 Kohlenstoffatomen bedeuten, wobei a) R , R2 und Rg zusammen wenigstens 5 Kohlenstoffatome besitzen, a) R, R2 and RG together have at least 5 carbon atoms, b) wenn R* ein Wasserstoffatom ist, Rg eine Alkylgruppe mit 2 bis 5 Kohlenstoffatomen und Rg eine Alkylgruppe mit 3 bis 5 Kohlenstoffatomen bedeutet und wenigstens eine der Gruppen Rg und Rg verzweigt ist, b) when R * is a hydrogen atom, RG an alkyl group of 2 to 5 carbon atoms and RG an alkyl group having 3 to 5 carbon atoms and at least one of the groups RG and RG is branched, 20 c) Ri, Rr, Η® · and R ^ V together have a total of 1 to 8 carbon atoms and 20 c) Ri, Rr, Η®· und R^V zusammen insgesamt 1 bis 8 Kohlenstoffatome besitzen und d) at least two of the groups r \ R ^ and RIE and R ^ V are hydrogen atoms and, when R ^ and and r! V are both hydrogen atoms, and RIR a methyl group, then RR a methyl, ethyl, n-propyl or straight-chain or branched-chain butyl or amyl group, as an additive in particular to cosmetic products and toiletries such as cleaning tissues and toothpicks 25, but not to foods and stimulants for humans or medicines and tobacco monopolists as Cooling agent for the human skin. d) wenigstens zwei der Gruppen r\ R^ und rIE und R^V Wasserstoffatome bedeuten und, wenn R^ und und r!V beide Wasserstoffatome bedeuten und RIR eine Methylgruppe ist, sodann RR eine Methyl-, Äthyl-, n-Propyl- oder geradkettige oder verzweigtkettige Butyl- oder Amylgruppe bedeutet, als Zusatz insbesondere zu kosmetischen Mitteln sowie Toiletteartikeln wie z.B. Reinigungsgewebe und 25 Zahnstochern, nicht jedoch zu Nahrungs- und Genußmitteln für Menschen oder Heilmitteln sowie Tabakmonopolgegenständen als kühlender Wirkstoff für die menschliche Haut.
- 2Verwendung von Carboxamiden der Formel (I), worin R , Rg und Rg jeweils Alkylgruppen mit 1 bis 5 Kohlenstoffatomen bedeuten, für den Zweck nach Anspruch 1. Second Use of carboxamides of the formula (I) in which R, RG and RG each represents alkyl groups having 1 to 5 carbon atoms, for the purpose of claim 1.
- 3Verwendung von Carboxamiden der Formel (I), worin R4 eine Methyl-, Äthyl- oder n-Propylgruppe 30 bedeutet und wenigstens eine der Gruppen R„ und R, eine verzweigtkettige Alkylgruppe mit einer Verzweigung in einer a- oder ß-Stellung bezüglich des mit (*) markierten Kohlenstoffatoms ist, für den Zweck nach Anspruch 1. Third Use of carboxamides of the formula (I) in which R4 is a methyl, ethyl or n-propyl group and at least one of R "and R is a branched chain alkyl group having a branch in an α or β position with respect to the carbon atom marked with (*), for the purpose of Claim 1.
- 4Verwendung von Carboxamiden der Formel (I), worin R , Rg und Rg zusammen 4th Use of carboxamides of the formula (I) in which R, RG and RG together
- 55 have up to 10 carbon atoms, for the purpose of claim 1. 5 bis 10 Kohlenstoffatome besitzen, fiir den Zweck nach Anspruch 1. 35 5. Use of carboxamides of the formula (Π), wherein one of the groups R1 and RR a hydrogen atom and the other group is an alkyl group and one of the groups R ^ and R ^ is a hydrogen atom and the other group is an alkyl group, for the purpose of claim 1. 35 5. Verwendung von Carboxamiden der Formel (Π), worin eine der Gruppen R1 und RR ein Wasserstoffatom und die andere Gruppe eine Alkylgruppe und eine der Gruppen R^ und R^ ein Wasserstoffatom und die andere Gruppe eine Alkylgruppe bedeutet, fiir den Zweck nach Anspruch 1.
- 6Verwendung von Carboxamiden der Formel (H), worin R1 eine Alkylgruppe bedeutet, fiir den Zweck nach Anspruch 1. 6th Use of carboxamides of the formula (H) in which R1 an alkyl group, for the purpose of claim 1. Druok:Ing. E. Voytjech, Vienna Druok: Ing. E. Voytjech, Wien
Independent claims6
328 paragraphs in 3 sections, as filed
@ Start of patent duration: 1975 10 15 Longest possible duration:
@ Issued on: 1976 07 26 uz) Inventors:
(60) Dependence:
OE 330963
@) References contemplated by the prior art: BS-PS3644653
No. 330963
The invention relates to the use of cooling agents as an adjunct to topically applied cosmetic compositions and other articles having a physiological cooling effect on the skin including the mucous membranes of the body, especially the mucous membranes of the respiratory tract.
Menthol is known for its physiological cooling effect on the skin and mucous membranes of the mouth 5 and has been widely used as a flavoring (menthol is a major constituent of peppermint oil) in foods, beverages, dentifrices, mouthwashes, etc., and as an ingredient in a large number of toilet articles , Ointments and lotions used for topical application. Menthol is also known as a tobacco additive to create a cool mouthfeel when smoking. Carbomenthol has also been reported to have a physiological cooling effect, as well as N, N-dimethyl-2-ethylbutanamide and
N, N-diethyl-2-ethylbutanamide, s. the french Patent No. 1,572,332.
It is known that the cooling effect of menthol is a physiological effect due to the direct action of menthol on the nerve endings of the human body, which are responsible for the perception of hot or cold, and that the cooling effect is not due to a latent heat of vaporization. It is believed that menthol acts as a direct stimulant on the cold receptors at the nerve endings, which in turn stimulate the central nervous system.
Although menthol is well known as a physiological coolant, in some compositions its use is limited by its strong peppermint-like odor.
The invention is based on the discovery that certain other organic compounds that can be readily synthesized have a physiological cooling effect similar to that obtained with menthol, but not the strong peppermint odor. In many cases, the compounds have very little or no odor. Such compounds therefore find use as additives in a wide range of topically applicable cosmetic compositions.
The compounds having a physiological cooling effect used according to the invention are carboxamides of the general formulas
R.
R -C-CONRR 2 | 4 5
R "or <sup>rly</sup>\ /
YY
CONR.R, if <sup>5</sup>
<img file="AT330963B_D0001.tif" />
R<sup>1</sup> (I) (II) wherein R ^ and R<sub>5</sub> each represents hydrogen atoms, alkyl groups having from 1 to 5 carbon atoms, or hydroxyalkyl groups having from 1 to 8 carbon atoms and having in total not more than 8 carbon atoms and, when R, a hydrogen atom, R<sub>c</sub> may also be an alkylcarboxyalkyl group of up to 6 carbon atoms, or R and R "taken together represent an alkylene group of up to 6 carbon atoms, the ends of which are attached to the amide nitrogen atom and thus form a nitrogen heterocycle, the carbon atom chain of which may optionally be interrupted by oxygen, R ^ Ri, RU, R 1 and R 1 are hydrogen atoms or alkyl groups of 1 to 5 carbon atoms, and R "and R" are each alkyl groups of 1 to 5 carbon atoms, where R, R "and R, together have at least 5 carbon atoms,
3 preferably 5 to 10 carbon atoms, further wherein when a hydrogen atom,
R is an alkyl group having 2 to 5 carbon atoms and R is an alkyl group having 3 to 5 carbon atoms and at least one of R groups<sub>2</sub> and R<sub>3</sub> is branched, preferably in the a- or / 3-position with respect to the (x) in the formula (I) carbon atom, further wherein Ri, RÜ, RÜI and RlV together contain 1 to 8 carbon atoms and wherein at least two of the groups R<sup>1</sup>, RÜ, RÜI and R<sup>1</sup>^ Are hydrogen atoms and, when Ri and Rl ^ both represent hydrogen atoms and RÜI is a methyl group, then RÜ means a methyl, ethyl, n-propyl or straight-chain or branched butyl or amyl group, as an additive in particular to cosmetic agents , such as B. After shave lotions, shaving soaps, shaving creams and shaving cream, toilet water, deodorants and antiperspirants, solid colognes, toilet soaps, bath oils and bath salts, shampoos, hair oils, talcum powders, face creams, hand creams, suntan lotions, dentifrices, mouthwashes, hair tonics, eye drops as well
Toiletries such. As cleaning tissues and toothpicks, but not to foods and stimulants for humans or medicines and tobacco monopoly articles as a cooling agent for human skin.
When the compounds of the invention contain an asymmetric carbon atom, any of the optical isomers can be used in pure form, but generally a mixture of the 50 optical isomers is used. In some cases, the degree of cooling effect produced by the compounds on the skin differs for the optical isomers, and in this case one or the other Iso3
No. 330,963 would be preferred. Likewise, the compounds of formula (II) exhibit geometric isomers and are commonly used as a mixture of isomers. However, in some cases, one or the other geometric isomers may be preferred.
The preferred acyclic carboxamides of formula (I) used in accordance with the invention are the tertiary compounds, ie those in which each of the groups R 1 R 3<sub>?</sub> and R<sub>s</sub> represents an alkyl group having 1 to 5 carbon atoms, and especially those wherein R<sub>t</sub> a methyl, ethyl or n-propyl group and at least one of the groups R<sub>2</sub> and R<sub>G</sub> is a branched chain group having a branch in an a or ^ position with respect to the carbon atom marked with (*) in the formula. Also preferred are monosubstituted amides, ie those in which R is<sub>4</sub> represents a hydrogen atom, and disubstituted amides wherein 10 R<sub>4</sub> and R<sub>G</sub> Mean methyl or ethyl groups. Another preferred group consists of amides of the formula (I) wherein R<sub>}</sub> is a hydrogen atom and at least one of the groups R<sub>2</sub> and Rgin a position is branched with respect to the carbon atom marked with (*) in the formula.
The preferred cyclohexane carboxamides of the formula (II) which are used according to the invention are cyclohexanecarboxamides having either one or two alkylkem substituents, wherein the alkylkene moiety in the case of mononuclear substituted compounds is in either the 1- or the 2-position and in the case of dicomain substituted compounds the first alkyl substituent is either in the 1- or the 2-position and the second alkyl substituent is either in the 1-position or the 2-position 5 or 6 position. Particularly preferred are tertiary compounds, ie those in which R is<sup>1</sup> an alkyl group. Generally, it is preferred that an alkyl group, preferably R<sup>1</sup>, is a branched chain group having a branch in an a or / 3 position with respect to the ring. Again, the monosubstituted cyclic carboxamides, ie those in which one of the groups R<sub>4</sub> and R ^ represents a hydrogen atom, and disubstituted cyclic carboxamides, wherein R<sub>4</sub> and R<sub>G</sub> Methyl or ethyl groups, preferably.
The amides can be readily prepared by conventional methods such as by reacting an acid chloride of the formula
RRR, COC1
2 o or
<img file="AT330963B_D0002.tif" />
R<sup>1</sup> COCI RiV \ / rII
Rin with an amine of the formula
HNR.R.
5 in the presence of a hydrochloric acid acceptor. Such reactions are common, and the methods involved are obvious to those skilled in the art.
Typical carboxamides of formula (I) which are useful in the compositions or articles of the invention are listed in Table I together with the indication of their cooling activity. The more stars are indicated, the greater the activity, ie the greater the cooling effect of a particular one
Quantity of connection is generated.
Table I
<td><sup>R</sup>!</td><td><sup>R</sup>2</td><td><sup>R</sup>3</td><td><sup>R</sup>4</td><td><sup>R</sup>5</td><td>activity</td>
<td><sup>CH</sup>3</td><td>iso-C ^ -</td><td>iso-C ^ -</td><td>H-</td><td><sup>C</sup>2V</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H<sub>7</sub>-</td><td>iso-CJ ^ -</td><td>H-</td><td>iso-CgE ^ -</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H-</td><td>iso-CJ ^ -</td><td>H-</td><td>ch<sub>3</sub>-</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H-</td><td>iso-CJ ^ -</td><td>H-</td><td>HIGH<sub>2</sub>C (CH<sub>3</sub>^ -</td><td>*****</td>
No. 330963
Table I (continued)
<td>R.</td><td>R "</td><td>R "</td><td>R</td><td>R</td><td rowspan="2">activity</td>
<td>i</td><td>2</td><td>3</td><td>4</td><td>5</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H<sub>r</sub></td><td>iso-OFT</td><td><sup>CH</sup>3</td><td>CH-</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H<sub>7</sub>-</td><td>iso-OFT</td><td>H-</td><td>tert. CH 4 9</td><td>*****</td>
<td><sup>C</sup>Ä-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>iso-C<sub>Ä</sub>-</td><td>H-</td><td><sup>C</sup>2V</td><td>*****</td>
<td><sup>C</sup>2<sup>H</sup>5</td><td><sup>C</sup>2<sup>H</sup>5</td><td>iso-Cjft-</td><td>CH 2 5</td><td><sup>C</sup>2<sup>H</sup>5</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H<sub>7</sub>-</td><td>iso-c ^ -</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>*****</td>
<td><sup>C</sup>A-</td><td>iso-C<sub>3</sub>H<sub>7</sub>-</td><td>iso-C<sub>3</sub>H<sub>7</sub>-</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>*****</td>
<td>H-</td><td>sec. C<sub>4</sub>H<sub>3</sub>-</td><td>sec. CH 4 9</td><td>H-</td><td>sec. CH 4 9</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H<sub>7</sub>-</td><td>nC H 4 9</td><td><sup>CH</sup>3</td><td><sup>0H</sup>a</td><td>*****</td>
<td>H-</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>sec. C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>sec. C, H 4 9</td><td>sec. C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>*****</td>
<td>ch<sub>3</sub>-</td><td>iso-C<sub>3</sub>H<sub>7</sub>-</td><td>iso-C 1<sub>7</sub>-</td><td>H-</td><td>c<sub>2</sub>H<sub>5</sub>° ° c<sup>cH</sup>2</td><td>****</td>
<td>C, H<sub>b</sub>-</td><td>CH -</td><td>CH -</td><td>H-</td><td>CH -</td><td>****</td>
<td>2 5</td><td>2 5</td><td>2 5</td><td></td><td>2 5</td><td></td>
<td>CH<sub>S</sub>-</td><td>sec. CH 4 9</td><td>sec. CH4 9</td><td>H-</td><td>iso-C ^ -</td><td>****</td>
<td>ch<sub>3</sub>-</td><td>1 SO-C -</td><td>aW</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>****</td>
<td>CH "-</td><td>iso-CH -</td><td>iso-C H -</td><td>H-</td><td>CH -</td><td>****</td>
<td>3</td><td>4 9</td><td>4 9</td><td></td><td>2 5</td><td></td>
<td>CH-</td><td>CH<sub>3</sub>-</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>****</td>
<td>ch<sub>3</sub>-</td><td>ch<sub>3</sub>-</td><td>iso-C<sub>4</sub>H<sub>G</sub>-</td><td>CH<sub>3</sub>-</td><td>CHG</td><td>****</td>
<td>H-</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td>c<sub>2</sub>H<sub>5</sub>° occh2-</td><td>****</td>
<td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>sec. C<sub>4</sub>H<sub>G</sub>-</td><td>ch<sub>3</sub>-</td><td>ch<sub>3</sub>-</td><td>****</td>
<td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>sec. CH 4 9</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>****</td>
<td>H-</td><td>XSO-C<sub>4</sub>H<sub>9</sub>-</td><td>sec. CH 4 9</td><td>H-</td><td>CHOOCCH 2 5 2</td><td>****</td>
<td>H-</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>sec. CH4 9</td><td>H-</td><td>HIGH<sub>2</sub>C (CHg)<sub>2</sub>-</td><td>****</td>
<td></td><td></td><td></td><td colspan="2">CH-CH.</td><td></td>
<td><sup>CH</sup>3</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>iso-C<sub>4</sub>H9</td><td>1 <sup>2</sup></td><td rowspan="2"><sup>2</sup>\</td><td>****</td>
<td></td><td></td><td></td><td>ch<sub>2</sub>-ce</td><td></td>
<td>ch<sub>3</sub>-</td><td>1 SO-C -</td><td>iso-C</td><td>Η-</td><td><sup>C</sup>2<sup>H</sup>5<sup>OOCCH</sup>2</td><td>***</td>
<td><sup>C</sup>2V</td><td><sup>C</sup>2<sup>H</sup>5</td><td><sup>C</sup>2<sup>H</sup>5</td><td>H-</td><td>HIGH<sub>2</sub>C (CHg)<sub>2</sub></td><td>***</td>
<td>CH-</td><td>sec. CH</td><td>sec. CH</td><td>H-</td><td>HIGH CH -</td><td>***</td>
<td>3</td><td>4 9</td><td>4 9</td><td></td><td>2 2</td><td></td>
No. 330
Table I (continued)
<td><sup>R</sup>!</td><td><sup>R</sup>2</td><td><sup>R</sup>3</td><td><sup>R</sup>4</td><td><sup>R</sup>5</td><td>activity</td>
<td>CH<sub>S</sub>-</td><td>sec. C<sub>4</sub>H<sub>3</sub>-</td><td>sec. CH4 y</td><td>H-</td><td>H-</td><td>***</td>
<td>CH<sub>f</sub></td><td>iso-C<sub>4</sub>H-</td><td>iso-C ^ I-</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>***</td>
<td>H-</td><td>iso-CjHy-</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>***</td>
<td>H-</td><td>iso-C<sub>4</sub>H<sub>G</sub>-</td><td>ieo-CFL</td><td>H-</td><td>c<sub>2</sub>H<sub>5</sub>OOCCH<sub>2</sub>-</td><td>***</td>
<td>H-</td><td>iso-C ^ -</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td><sup>C</sup>2<sup>H</sup>5<sup>OOGCH</sup>2</td><td>**</td>
<td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>iso-C ^ -</td><td>ch<sub>3</sub>-</td><td><sup>CH</sup>3</td><td>* #</td>
<td>H-</td><td>iso-C<sub>4</sub>H<sub>G</sub>-</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td>HIGH<sub>2</sub>C (CH<sub>s</sub>)<sub>2</sub>-</td><td>**</td>
<td>H-</td><td><sup>C</sup>2<sup>H</sup>5</td><td>iso-CJH - 11</td><td>H-</td><td><sup>C</sup>2<sup>R</sup>5</td><td>**</td>
<td>ch<sub>3</sub>-</td><td>iso-CJI<sub>r</sub></td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td><</td><td>CH-CH 2 2 \ CH-CH / 2 2</td><td>**</td>
<td>H-</td><td>iso-C ^ -</td><td>iso-C ^ -</td><td>H-</td><td>iso-CgHj-</td><td>****</td>
<td><sup>C</sup>2<sup>H</sup>5</td><td><sup>C</sup>2<sup>R</sup>5</td><td><sup>C</sup>2<sup>H</sup>5</td><td>ch<sub>3</sub>-</td><td>ch<sub>3</sub>-</td><td>*</td>
<td>ch<sub>3</sub>-</td><td><sup>C</sup>2<sup>R</sup>5</td><td><sup>C</sup>2<sup>H</sup>5</td><td>ch<sub>3</sub>-</td><td></td><td>*</td>
<td>ch<sub>3</sub>-</td><td><sup>C</sup>2<sup>H</sup>5</td><td><sup>C</sup>2<sup>H</sup><</td><td>H-</td><td>c<sub>2</sub>H<sub>5</sub>cocch<sub>2</sub>-</td><td>*</td>
<td>CH-</td><td><sup>CH</sup>3 '</td><td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td>CH.OOCCH - 2 5 2</td><td>#</td>
<td>H-</td><td><sup>C</sup>2<sup>R</sup>5</td><td>sec. C<sub>4</sub>H<sub>9</sub>-</td><td>H-</td><td>HIGH<sub>2</sub>C (C h ^ -</td><td>*</td>
<td>ch<sub>3</sub>-</td><td>iso-C ^ -</td><td>iso-c ^ -</td><td>H-</td><td>H-</td><td>*</td>
<td><sup>C</sup>2<sup>H</sup>5</td><td><sup>C</sup>2<sup>R</sup>5</td><td>iso-C ^ -</td><td>H-</td><td><sup>B</sup>-</td><td>*</td>
Typical cyclic amides of the formula (II) which are useful according to the invention are listed in the following Table H.
Table II
<td>rl</td><td>Rll</td><td>Rin</td><td>RLV</td><td><sup>R</sup>4</td><td><sup>R</sup>5</td><td>activity</td>
<td>iso-C ^ -</td><td>H</td><td>H</td><td>H</td><td>H</td><td>W</td><td>*****</td>
<td>iSO C ^ -</td><td>H</td><td>H</td><td>H</td><td rowspan="2"><sup>CH</sup>3 CH-CH<sub>X</sub>1 <sup>2 2</sup>> <sup>CH</sup>2<sup>CH</sup>2</td><td><sup>CH</sup>3</td><td>*****</td>
<td>iso-CGH? -</td><td>H</td><td>H</td><td>H</td><td></td><td>*****</td>
<td>nC ^ -</td><td>H</td><td>H</td><td>H</td><td><sup>CH</sup>3</td><td>ch<sub>3</sub>-</td><td>*****</td>
<td>iso-C ^ -</td><td>ch<sub>3</sub>-</td><td>H</td><td>H</td><td>H</td><td><sup>C</sup>2<sup>H</sup>3</td><td>*****</td>
Nr.330963
Table II (continued)
<td>R<sup>1</sup></td><td>R<sup>n</sup></td><td>R<sup>m</sup></td><td>RiV</td><td>* 4</td><td>* 5</td><td>activity</td>
<td>sec. C<sub>4</sub>H<sub>f</sub></td><td>H</td><td>H</td><td>Η</td><td>H</td><td>W</td><td>*****</td>
<td>iso-C<sub>4</sub>H-</td><td></td><td>H</td><td>H</td><td>H</td><td><sup>G</sup>2<sup>H</sup>r</td><td>*****</td>
<td>iso-C<sub>4</sub>H<sub>9</sub>-</td><td><sup>CH</sup>f</td><td>H</td><td>H</td><td>H</td><td>HIGH<sub>2</sub>C (CH ^<sub>2</sub>-</td><td>Hey ****</td>
<td>iso-C<sub>4</sub>H<sub>G</sub>-</td><td>ch<sub>3</sub>-</td><td>H</td><td>H</td><td>ch<sub>3</sub>-</td><td>ch<sub>3</sub>-</td><td>*****</td>
<td><sup>C</sup>A-</td><td>W</td><td>H</td><td>H</td><td>H</td><td><sup>C</sup>2<sup>H</sup>5</td><td>*****</td>
<td>nC ^ -</td><td>H</td><td>H</td><td>H</td><td>H</td><td>nC<sub>4</sub>H<sub>9</sub>-</td><td>****</td>
<td><sup>C</sup>A-</td><td>ch<sub>3</sub>-</td><td>H</td><td>H</td><td>H</td><td><sup>C</sup>2<sup>H</sup>5</td><td>****</td>
<td><sup>C</sup>2<sup>H</sup>5</td><td>ch<sub>3</sub>-</td><td>H</td><td>H</td><td>H</td><td>HIGH<sub>2</sub>C (CH ^<sub>2</sub>-</td><td>****</td>
<td><sup>C</sup>2<sup>H</sup>5</td><td>CH-</td><td>H</td><td>H</td><td>ch<sub>3</sub>-</td><td>ch<sub>3</sub>-</td><td>****</td>
<td><sup>C</sup>2<sup>H</sup>5</td><td><sup>C</sup>2<sup>H</sup>5</td><td>H</td><td>H</td><td>Η</td><td>ch<sub>3</sub>-</td><td>****</td>
<td>H</td><td>CH2 5</td><td>H</td><td>H</td><td>Η</td><td><sup>C</sup>2<sup>H</sup>5</td><td>****</td>
<td>sec. CH 4 9</td><td>H</td><td>H</td><td>H</td><td>ch<sub>3</sub>-</td><td><sup>CH</sup>f</td><td>****</td>
<td>ch<sub>3</sub>-</td><td>H</td><td>H</td><td>H</td><td>H</td><td>CH 2 5</td><td>***</td>
<td>nC ^ -</td><td>Ξ</td><td>H</td><td>H</td><td>H</td><td>CH - 2 5</td><td>***</td>
<td>nC<sub>A</sub>-</td><td>H</td><td>H</td><td>H</td><td colspan="2">-CH CH "OCH CH2 2 2 2</td><td>***</td>
<td>H</td><td><sup>n</sup>-<sup>C</sup>4<sup>H</sup>3</td><td>H</td><td>H</td><td>H</td><td><sup>C</sup>2<sup>H</sup>5</td><td>***</td>
<td><sup>C</sup>2<sup>H</sup>5</td><td><sup>C</sup>2<sup>H</sup>5</td><td>H</td><td>H</td><td>H</td><td>HIGH<sub>2</sub>C (CH ^<sub>2</sub>-</td><td>***</td>
<td><sup>CH</sup>3</td><td>H</td><td>H</td><td>H</td><td>H</td><td><sup>Q</sup>-<sup>C</sup>A</td><td>**</td>
<td>H</td><td>ch<sub>3</sub>-</td><td>H</td><td>H</td><td>H</td><td><sup>C</sup>2<sup>H</sup>5</td><td>**</td>
<td>H</td><td><sup>C</sup>2<sup>H</sup>5</td><td>H</td><td>H</td><td>H</td><td>C HOOCCH - 2 5 2</td><td>**</td>
<td>H</td><td><sup>C</sup>2<sup>H</sup>5</td><td>H</td><td>H</td><td>H</td><td>HIGH<sub>2</sub>C (CH ^<sub>2</sub>-</td><td>**</td>
<td>sec. CH 4 9</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td>**</td>
<td>iso-C $ -</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td>**</td>
<td>nC ^ -</td><td>H</td><td>Ξ</td><td>H</td><td>H</td><td>H</td><td>**</td>
<td>H</td><td><sup>n</sup>"<sup>C</sup>A ~</td><td>H</td><td>H</td><td>H</td><td>c<sub>2</sub>H<sub>5</sub><sup>O</sup>° cch<sub>2</sub>-</td><td>*</td>
<td>H</td><td>ch<sub>3</sub>-</td><td>ch<sub>3</sub>-</td><td>H</td><td>H</td><td><sup>C</sup>2<sup>H</sup>5</td><td>*</td>
The compounds are useful in pharmaceutical preparations in a wide variety of cosmetic compositions.
No. 330963
These can be applied locally, u. zw. either on the outer surface of the human body, such. As perfumes, powders and other toilet preparations, lotions, oils and creams, or on the inner mucous membranes of the body, or in normal use with these come into contact, such as with the mucous membranes of the mouth or throat, u. tw. irrespective of whether by direct or indirect application or inhalation, this term includes mouthwashes, dentifrices, mouth washes and chewing gum. Also included within the spirit of the invention are toiletry articles such as cleansing tissues and toothpicks which are impregnated or coated with the active cooling compound.
Another class of compositions within the inventive concept are articles such as pipe and cigarette filters, especially filter mouthpieces and filter tips for cigarettes.
According to the invention, an amount of the active cooling compounds in the compositions is used which is sufficient to stimulate the cold receptors in the areas of the skin or mucous membrane with which the compositions come into contact and thereby produce the desired sensation of coldness. Since the degree and the length of cooling sensation from compound to compound is different, the amount of stimulant used in each composition also varies greatly. As a guide, it can be said that with the more active compounds a strong cooling sensation when applied to the skin of as little as 0.05 ml of a 1 wt. -% solution of the active ingredient is produced in ethanol. For the less active compounds, a strong cooling sensation is achieved only with more concentrated solutions, such as 5% by weight or more of the active ingredient. It must also be admitted that such skin tests are somewhat subjective, with individual subjects having a greater or lesser cooling sensation than others when subjected to the same test.
The active cooling compound according to the invention is incorporated in a carrier which may be completely inert or which may consist of or contain other active ingredients. A wide variety of carriers are suitable, depending on the end use of the agent, such as carriers in the form of solids, liquids, emulsions, foams or gels. Typical carriers for the active cooling compounds are aqueous or alcoholic solutions, oils and fats such as hydrocarbon oils, fatty acid esters, long chain alcohols and silicone oils, finely divided solids such as starch or talc, cellulosic materials such as paper tissue, low boiling hydrocarbons, and halogenated hydrocarbons used as aerosol propellants used are gums and natural or synthetic resins.
In most compositions, the carrier will contain one or more of the following as additives: flavoring, coloring or odorants or surfactants.
The following discussion explains the range of compositions in which the active cooling compounds of the invention can be used:
Toilet articles or preparations, such as aftershave lotions, shaving soaps, shaving creams and shaving creams, toilet waters, deodorants and antiperspirants, firm colognes, toilet soaps, bath oils and bath salts, shampoos, hair oils, talcum powders, face creams, hand creams, sunscreen lotions, cleansing tissues, dentifrices, toothpicks , Mouthwashes, hair tonics and cosmetic eye drops, cosmetic hair ointments, creams and lotions, and filter mouthpieces, Filter tips for cigarettes and various preparations, such as water-soluble adhesive compositions for
Envelopes, stamps, adhesive labels, etc. and chewing gum.
Because of the cooling sensation on the skin, the main usefulness of the cooling compounds used in the present invention is in the wide range of toilet preparations and toiletries. The specific preparations discussed below are given by way of example only.
More usefulness is in the field of after-shave lotions, toilet waters, etc. in which the compounds are used in alcoholic or aqueous-alcoholic solution, such solutions usually containing a perfume or a mild disinfecting agent or both. The amounts of the compounds added thereto are generally in the range from 0.1 to 10% by weight.
Another field of application is that of soaps, shampoos, bath oils, etc., where the compound is used in combination with an oil or fat or a natural or synthetic surfactant, such as a fatty acid salt or a lauroyl sulfate salt, which composition is also usually an ethereal one Contains oil or perfume. The range of soap compositions includes soaps of all kinds, such as toilet soaps, shaving soaps, shaving cream, etc. Usually, the compound is added in compositions in an amount of 1.0 to 10% by weight. Another class of toilet preparations into which compounds of the invention can be incorporated are, for example, cosmetic creams and emollients, such as those usually based on emulsions and optionally a number of ingredients containing , such as waxes, preservatives, perfumes, disinfecting substances, astringents, pigments, etc. Within this class are also lipstick compositions, such as compositions usually containing an oil and wax base in which the compounds, along with the conventional ingredients such as pigments, perfumes, etc., are used
No. 330,963 can be used according to the invention. Again, the formulation of such preparations is conventional except for the incorporation of the cooling compound, wherein the cooling compound is usually incorporated in an amount of 0.05 to 10.0% by weight.
Oral hygiene products containing the cooling compounds include mouthwashes and dentifrices.
Mouthwashes usually comprise an aqueous, alcoholic or aqueous-alcoholic solution of a disinfectant which is often dyed or flavored to produce a better flavor and to which the refrigerant is added in an amount of 0.1 to 1.0 wt. % added.
Dentifrices may be in the form of solid blocks, powders, pastes or liquids, and usually contain a finely divided abrasive or polishing material such as precipitated chalk, silica, magnesium silicate, aluminum hydroxide or other similar materials known in the art, as well as a detergent or foaming agent , Optional ingredients which may also be incorporated are flavoring and coloring agents, disinfecting agents, lubricants, thickening agents, emulsifying or plasticizing agents. The amount of cooling compounds added to such preparations is generally in the range of 0.1 to 5.0% by weight.
An advantageous use according to the invention of the cooling active substances is also that in pipe or cigarette filters, especially in cigarette filter mouthpieces. The filter material pad, which may be of any known type, such as Ceuuioseacetat, paper, cotton, a-cellulose or As20 bestfasem is simply impregnated with an alcoholic solution of the cooling agent and is then dried, wherein the cooling agent in the filter pad reflected. The effect is a pleasant cool sensation in the mouth when the cigarette is smoked. Already 0.1 mg of the cooling agent is effective.
The following examples further illustrate the invention.
The percentages represent weight percentages.
Example 1: Aftershave lotion.
A post-shave lotion was prepared according to the following recipe by dissolving the ingredients of the liquid followed by cooling and filtering.
<td>Denatured ethanol</td><td>75%</td>
<td>diethyl phthalate</td><td>1.0%</td>
<td>propylene glycol</td><td>1.0%</td>
<td>lactic acid</td><td>1.0%</td>
<td>Perfume</td><td>3.0%</td>
<td>water</td><td>to 100%</td>
0.5% by weight of N, 2,3-trimethyl-2-isopropylbutanamide were incorporated into the base lotion.
When the finished lotion was applied to the face, a clearly noticeable cooling effect was perceived after a short time.
Example 2: Toothpaste.
The following ingredients were processed together in a mixer:
<td>dicalcium</td><td>48%</td>
<td>sodium lauryl sulfate</td><td>2.5%</td>
<td>glycerin</td><td>24.8%</td>
<td>sodium</td><td>2.0%</td>
<td>Sodium saccharine</td><td>0.5%</td>
<td>Citrus flavor</td><td>1.0%</td>
<td>water</td><td>to 100%</td>
Shortly before the end of the mixing, 1.0% by weight of N, N, 2,3-tetramethyl-2-isopropylbutanamide was added to the mixer.
When used as a toothpaste, a cooling effect was noted in the mouth.
Example 3: Aerosol Shaving Soap.
An aerosol shaving soap composition was formulated according to the following recipe:
No. 330963
<td>stearic acid</td><td>6.3%</td>
<td>lauric acid</td><td>2.7%</td>
<td>triethanolamine</td><td>4.6%</td>
<td>sodium</td><td>0.1%</td>
<td>sorbitol</td><td>5.0%</td>
<td>perfume</td><td>0.4%</td>
<td>water</td><td>to 100%</td>
The composition was prepared by combining the acids in water, whereupon the triethanolamine was added, the mixture cooled and the other ingredients added. To this mixture was then added 0.5% N, 2,2-triethyl-3-methylbutanamide. The composition was then packaged in an aerosol container under pressure of a butane propellant.
When used in the base, a fresh cool feeling was strongly noticeable on the face.
Example 4: Toilet water.
A toilet water was prepared according to the following recipe:
Denatured ethanol 75.0%
Perfume 5.0%
Water to 100%
2.0%, based on the total composition, of 2-sec. Butyl-2,3-di20 methylpentanamid added.
As with the aftershave lotion on the skin a cooling effect was clearly visible, u. for a long time after the end of the cooling effect, which could be traced to the evaporation of the alcoholic carrier.
Example 5: Deodorant.
A deodorant suitable for delivery as an aerosol under pressure with a suitable propellant was prepared as follows:
<td>Denatured ethanol</td><td>96.9%</td>
<td>hexachlorophene</td><td>2.0%</td>
<td>isopropyl</td><td>1.0%</td>
<td>Perfume</td><td>0.1%</td>
2% by weight of N, N, 2,2-tetraethyl-3-methylbutanamide were added to this composition. The application of the finished product resulted in a significant cooling effect on the skin.
Example 6: Hair shampoo.
Sodium lauryl ether sulfate was dispersed in 90 g of water in a high speed mill. To this dispersion was added 2% by weight of N- (1,1-dimethyl-2-hydroxyethyl) -2-isopropyl-2,3-dimethyl-35-butanamide. If the hair has been washed using this shampoo, you will notice a fresh, cool sensation on the scalp.
Example 7: Solid cologne water.
A solid cologne was prepared according to the following recipe:
<td>Denatured ethanol</td><td>74.5%</td>
<td>propylene glycol</td><td>3.0%</td>
<td>sodium</td><td>5.0%</td>
<td>Perfume</td><td>5.0%</td>
<td>water</td><td>to 100%</td>
The sodium stearate was dissolved by stirring in a warm mixture of ethanol, propylene glycol 45 and water. To this solution was added the perfume and 2% N, N, 2-dimethyl-2-isopropyl-hexanamide, and the mixture was allowed to solidify to a waxy cake.
When it was applied to the face, a pronounced cooling effect was detectable.
Example 8: Mouthwash.
A concentrated mouthwash preparation was prepared according to the following recipe:
No. 330963
<td>ethanol</td><td>3.0%</td>
<td>borax</td><td>2.0%</td>
<td>sodium bicarbonate</td><td>1.0%</td>
<td>glycerin</td><td>10.0%</td>
<td>flavoring</td><td>0.4%</td>
<td>thymol</td><td>0.03%</td>
<td>water</td><td>to 100%</td>
To this composition was added 0.1% N- (1,1-dimethyl-2-hydroxyethyl) -2,2-diethylbutanamide. When diluting with about ten times the volume of water and when using to rinse the
Mouth received a cooling effect in the mouth.
Example 9: Toothpick.
The tip of a wooden toothpick was impregnated with an alcoholic solution containing N-ethyl-2,2-diisopropylbutanamide in sufficient quantity to precipitate on the toothpick 0.05 mg of the compound. The impregnated toothpick was then dried. When it was put on the tongue, no taste was noticeable, but a strong cooling effect was observed after a short time.
Example 10: Cleaning fabric.
A cleaning fluid was prepared according to the following recipe:
Triethanolamine lauryl sulfate 1.0%
Glycerine 2.0%
Perfume 0.95%
Water to 100%
To this liquid was added 1.0% N-ethyl-2-isopropyl-2,3-dimethylbutanamide. A paper towel was then soaked in the liquid. When the impregnated cloth was used to wipe the skin, a fresh, cool feeling appeared on the skin after a short time.
Example 11: Aftershave Lotion.
A post-shave lotion was prepared according to the following recipe by dissolving the ingredients of the liquid followed by cooling and filtering.
<td>Denatured ethanol</td><td>75%</td>
<td>diethyl phthalate</td><td>1.0%</td>
<td>propylene glycol</td><td>1.0%</td>
<td>lactic acid</td><td>1.0%</td>
<td>Perfume</td><td>3.0%</td>
<td>water</td><td>to 100%</td>
The basic lotion was 0.5% by weight, based on the total composition, of N, 2-di-sec. butyl35 -3-methylpentanamide incorporated. When the finished lotion was applied to the face, a clearly noticeable cooling effect was perceived after a short time.
Example 12: Aerosol Shaving Soap.
An aerosol shaving soap composition was formulated according to the following recipe:
<td>stearic acid</td><td>6.3%</td>
<td>lauric acid</td><td>2.7%</td>
<td>triethanolamine</td><td>4.6%</td>
<td>sodium</td><td>0.1%</td>
<td>sorbitol</td><td>5.0%</td>
<td>Perfume</td><td>0.4%</td>
<td>water</td><td>to 100%</td>
The composition was prepared by combining the acids in water, whereupon the triethanolamine was added, the mixture cooled and the other ingredients added. To this mixture was then 0.5%, based on the total composition, N-ethyl-2-sec. butyl-4-metylpentanamide added. The composition was then packaged in an aerosol container under 50 pressure of a butane propellant. When used in shaving, a fresh cool feeling was noticeable on the face.
No. 33096
Example 13: Aftershave lotion.
A post-shave lotion was prepared according to the following recipe by dissolving the ingredients of the liquid followed by cooling and filtering.
<td>Denatured ethanol</td><td>75%</td>
<td>diethyl phthalate</td><td>1.0%</td>
<td>propylene glycol</td><td>1.0%</td>
<td>lactic acid</td><td>1.0%</td>
<td>Perfume</td><td>3.0%</td>
<td>water</td><td>to 100%</td>
1.0% by weight, based on the total composition, of N-ethyl-2-methyl-1-isopropylcyclohexanamide was incorporated into the base lotion. When the finished lotion was applied to the face, a clearly noticeable cooling effect was perceived after a short time.
Example 14: Toothpaste.
The following ingredients were blended together in a blender:
<td>dicalcium</td><td>48.0%</td>
<td>sodium lauryl sulfate</td><td>2.5%</td>
<td>glycerin</td><td>24.8%</td>
<td>sodium</td><td>2.0%</td>
<td>Citrus flavor</td><td>1.0%</td>
<td>sodium</td><td>0.5%</td>
<td>water</td><td>to 100%</td>
Shortly before the end of the mixing, 1% by weight of N, N-dimethyl-1-isopropylcyclohexanamide was added to the mixer. When used as a toothpaste, a cooling effect was noted in the mouth.
Example 15: Aerosol Shaving Soap.
An aerosol shaving soap composition was prepared according to the following recipe:
<td>stearic acid</td><td>6.3%</td>
<td>lauric acid</td><td>2.7%</td>
<td>triethanolamine</td><td>4.6%</td>
<td>sodium</td><td>0.1%</td>
<td>sorbitol</td><td>5.0%</td>
<td>Perfume</td><td>0.4%</td>
<td>water</td><td>to 100%</td>
The composition was prepared by combining the acids in water, whereupon the triethanolamine was added, the mixture cooled and the other ingredients added. To this mixture was then added 2%, based on the total composition, of N, 2-diethylcyclohexanamide. The composition was then packaged in an aerosol container under pressure of a butane propellant.
When used in shaving, a fresh cool feeling was noticeable on the face.
Example 16: Toilet water.
A toilet water was prepared according to the following recipe:
Denatured ethanol 75.0%
Perfume 5.0%
Water to 100%
To this recipe was added 3.0%, based on the total composition, of N, N, 2-trimethyl-1-isobutylcyclohexanamide. As with the Nachrasurlotton a cooling effect was clearly visible on the skin,
u. for a long time after the end of the cooling effect, which could be traced to the evaporation of the alcoholic carrier.
Example 17: Deodorant.
A deodorant suitable for delivery as an aerosol under pressure with a suitable propellant was prepared as follows:
No. 330963
<td>Denatured ethanol</td><td>96.9%</td>
<td>hexachlorophene</td><td>2.0%</td>
<td>isopropyl</td><td>1.0%</td>
<td>Perfume</td><td>0.1%</td>
2.5% by weight of N- (2-hydroxy-1,1-dimethylethyl) -1-ethyl-2-methyl-bicyclohexanamide were added to this composition. The application of the finished product resulted in a significant cooling effect on the skin.
Example 18: Hair shampoo, g Sodium lauryl ether sulfate was dispersed in 90 g of water in a high-speed mill. To this dispersion was added 3.0% by weight of N-methyl-1,2-diethylcyclohexanamide. When the hair was washed using this shampoo, a fresh, cool sensation was noted on the scalp.
Example 19: Solid cologne water.
A solid cologne was prepared according to the following recipe:
<td>Denatured ethanol</td><td>74.5%</td>
<td>propylene glycol</td><td>3.0%</td>
<td>sodium</td><td>5.0%</td>
<td>Perfume</td><td>5.0%</td>
<td>water</td><td>to 100%</td>
The sodium stearate was dissolved by stirring in a warm mixture of the ethanol, propylene glycol and water. To this solution was added the perfume and 2.0% N-ethyl-l-sec. butyl cyclohexanamide was added and the mixture was allowed to solidify to a waxy cake.
When applied to the face, a pronounced cooling effect was noted.
Example 20: Mouthwash.
A concentrated mouthwash preparation was prepared according to the following recipe:
<td>ethanol</td><td>3.0%</td>
<td>borax</td><td>2.0%</td>
<td>sodium bicarbonate</td><td>1.0%</td>
<td>glycerin</td><td>10.0%</td>
<td>flavoring</td><td>0.4%</td>
<td>thymol</td><td>0.03%</td>
<td>water</td><td>to 100%</td>
To this composition was added 0.1% N-ethyl-1-isopropyl-2-methylcyclohexanamide. When diluting with about ten times the volume of water and when using the mouth, a cooling effect was obtained in the mouth.
Example 21: Toothpick.
The tip of a wooden toothpick was impregnated with an alcoholic solution containing N-ethyl-1-methylcyclohexanamide in sufficient quantity to precipitate 0.10 mg of the compound on the toothpick. The impregnated toothpick was then dried. If it was put on the tongue, no taste was noticeable, but after a short time a pronounced cooling effect was observed.
Example 22: Cleaning fabric.
A cleaning fluid was prepared according to the following recipe:
Triethanolamine lauryl sulfate 1.0%
Glycerine 2.0%
Perfume 0.95%
Water to 100%
To this liquid was added 2.0% N, 1,2-triethylcyclohexanamide. A paper towel was then soaked in the liquid.
When the impregnated cloth was used to wipe the skin, a fresh, cool feeling appeared on the skin after a short time.
No. 330963
Other compounds within the general formulas are equally suitable for use in compositions according to Examples 1 to 22, and the physiological cooling effect obtained with the use of compounds (I) and (II) according to the invention permits the use of these compounds in a wide range also other agents and compositions where a cooling effect is of value.
Contents3
Every citation, both ways
| Document | Relation | Office | Cited during |
|---|---|---|---|
| DE102008015428A1 | Cited by | Germany | Search report |
| DE102008015426A1 | Cited by | Germany | Search report |
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52 members in 27 offices
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| RO67320A | Romania | A | |
| US4230688A | United States of America | A | |
| PH14013A | Philippines | A | |
| SE418453B | Sweden | B | |
| US4296255A | United States of America | A | |
| DE2366423A1 | Germany | A1 | |
| DE2317538C2 | Germany | C2 | |
| NO148699B | Norway | B | |
| NO148699C | Norway | C | |
| DE2366423C2 | Germany | C2 | |
| JPS597744B2 | Japan | B2 | |
| JPS5935940B2 | Japan | B2 | |
| DE2317539C2 | Germany | C2 | |
| NL181164B | Netherlands (Kingdom of the) | B | |
| NL181164C | Netherlands (Kingdom of the) | C |
3 legal events, as the office reported them to INPADOC
Over the term
Point at a mark for the eventEvents
| Event | Code | |
|---|---|---|
| Ceased due to non-payment of the annual feeCeasedELJ | ELJ | |
| Change in the company nameEFA | EFA | |
| Ceased due to non-payment of the annual feeCeasedELJ | ELJ |
Numbers
- Application
- 348073
Titles2
- German
- KUHLMITTEL
- English
- coolant
Classification
- CPC, 18
- C12G3/06
- A24B15/32
- A61K8/02
- A61K8/0208
- A61K8/42
- A61K2800/244
- A61Q1/14
- A61Q5/02
- A61Q9/02
- A61Q11/00
- A61Q13/00
- A61Q15/00
- A61Q17/005
- A61Q19/00
- A61Q19/002
- A61Q19/10
- A23L27/202
- A23L27/2054
- IPC, 11
- A23L27 20
- A24B15 32
- A61K8 02
- A61K8 42
- A61Q1 14
- A61Q5 02
- A61Q9 02
- A61Q15 00
- A61Q19 00
- A61Q19 10
- C12G3 06