Oligoribonucleotides for influencing hair growth

The present invention relates to the use of oligoribonucleotides which induce the breakdown of the mRNA of proteins and enzymes which influence the hair cycle in a stimulating or inhibiting manner for the production of cosmetic or dermatological preparations for the treatment and prophylaxis of the reduced (hair loss, Hair miniaturization) or the undesirable (hypertrichosis) growth of hair on the scalp or body, such as those associated with age-related changes in hair growth.

The hair cycle-regulating proteins or enzymes primarily include hair growth-inhibiting proteins such as growth factors, in particular the members of the Tumor Growth Factor beta superfamily (TGFbeta) and their receptors (TGFbeta-R), and steroid receptors and steroid-catalyzing enzymes, in particular the androgen Receptor, and hair growth-promoting cellular signaling molecules, in particular the Sonic Hedgehog protein and the insulin-like growth factor 1 (IGF-1), understood.

Papillary hair is called the hair that is in the growth period, which is also called the anagen phase or anagen phase. In this phase, the hair is anchored in the skin with its papilla. About 80% of the scalp hair is in the anagen phase for about 2 to 5 years. In a subsequent transition phase (catagen phase), the hair migrates to the surface of the skin for about 2 weeks and then remains in a resting state (telogen phase) for about 3 to 4 months until it finally fails.

Hair loss that goes beyond normal levels or excessive hair growth on unwanted parts of the body is usually considered a serious cosmetic disorder, as are other hair growth disorders. For this reason, many agents have been proposed, for example for the treatment of hair loss and baldness, and hair restoration agents which are intended to maintain or promote the growth of the hair.

The growth of the hair follicle is subject to cyclic control, growth phases (anagen) alternate with rest phases (telogen), the transition between these phases is called catagen. Both the size of a hair follicle and the length of its hair shaft depend on the length of the anagen phase (usually 2 - 5 years) (Paus el al., 1998). A change in the normal hair cycle, in particular a shortening of the growth phase due to premature transition to the catagen / telogen, leads to the scalp pair regressing over several cycles and, as a result, to a drastic change in its biophysical properties.

Hair growth is determined by many endogenous and exogenous factors that can inhibit or promote it. In this context, it is known that the activity of the tumor growth factor beta 1 (TGFbeta-1) is decisive for the duration of the growth phase of the hair follicle, since TGFbeta-1 promotes the anagen-catagen transition and suppresses hair regeneration (Foitzik et al., 2000; Liu et al., 2001). The hair growth promoting effect can also be achieved by inhibiting the androgen receptor. This protein is expressed in the hair follicle and is responsible for the sensitivity of the follicular cells to androgenic hormones. As is known, these hormones are responsible for shortening the anagen phase and, if the hair follicles are sufficiently sensitive, cause deteriorated hair growth (Hibberts et al., 1998). Active ingredients that inhibit the synthesis of TGFbeta-1 and / or the androgen receptor therefore lead to improved hair formation (hair strengthening) and are therefore of great cosmetic use.

On the other hand, the inhibition of translation of genes that promote hair formation (e.g. the Sonic Hedgehog gene, Sato et al. (1999); or the gene of insulin-like growth factor 1, Su et al. (1999)) offers one Possibility to suppress unwanted hair growth. An inhibition of cellular sonic hedgehog synthesis accelerates the anagen-telogen transit, so that the hair follicle goes into the resting phase. The result is a shorter growth phase and thinner, less visible hair. This approach is particularly useful for use in the shaving or body area to reduce unwanted body hair.

More information can be found in

Paus, R. (1998) Principles of hair cycle control. J Dermatol. 25 (12): 793-802,

Foitzik K, Lindner G, Mueller-Roever S, Maurer M, Botchkareva N, Botchkarev V, Handjiski B, Metz M, Hibino T, Soma T, Dotto GP, Paus R (2000): Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo. FASEB J. 14 (5): 752-60,

Liu X, Alexander V, Vijayachandra K, Bhogte E, Diamond I, Glick A (2001): Conditional epidermal expression of TGFbeta 1 blocks neonatal lethality but causes a reversible hyperplasia and alopecia. Proc Natl Acad Sci USA 98 (16): 9139-44,

Hibberts, NA, AE Howell and Randall, VA (1998). "Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp." J Endocrinol 156 (1): 59-65.,

Sato, N., PL Leopold and Crystal, RG (1999). "Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog." J Clin Invest 104 (7): 855-864 and

Su, HY, JG Hickford, Bickerstaffe, R. and Palmer, BR (1999). "Insulin-like growth factor 1 and hair growth." Dermatol Online J 5 (2): 1.

Fire et al., Trends Genet. 15 (1999) 358-363 have shown that gene expression can be inhibited post-transcriptionally by the presence of double-stranded RNA fragments (dsRNA), which is homologous to the sequence of the mRNA of the gene under investigation, and this process as RNA interference (RNAi). designated. The dsRNA causes the specific degradation of the homologous mRNA in the cell in an as yet unexplained manner and thus prevents protein production.

WO01 / 29058 discloses the identification of genes which are involved in RNAi and their use for modulating RNAi activity.

Elbashir et al., Nature 411 (2001) 494-498, describe the specific inhibition of the expression of endogenous and heterologous genes in various mammalian cells by means of short, interfering RNAs (short interfering RNAs, siRNAs). Double-stranded RNA fragments with a length of 21 nucleotides were used.

The reduction in gene expression in cells by dsRNA is known from WO01 / 6883. The dsRNA contains a nucleotide sequence which, under the physiological conditions of the cell, hybridizes with the nucleotide sequence of at least part of the gene to be inhibited. The dsRNA is preferably 400 to 800 nucleotides in length.

WO01 / 75164 discloses the use of dsRNA with a length of 21 to 23 nucleotides for the specific inactivation of gene functions in mammalian cells by RNAi.

Brummelkamp et al., Science 296 (2002) 550-553, describe a vector system which is intended to trigger the synthesis of siRNAs in mammalian cells and thus to inhibit the gene expression of a target gene.

EP 1 214 945 A2 discloses the use of dsRNA with a length of 15 to 49 base pairs to inhibit the expression of a given target gene in mammalian cells. The dsRNA can be modified to increase its stability and is said to allow the treatment of cancer, viral diseases and Alzheimer's disease.

WO02 / 053773 relates to an in vitro method for determining skin stress and skin aging in humans and animals, test kits and biochips suitable for carrying out the method, and a test method for demonstrating the effectiveness of cosmetic or pharmaceutical active substances against skin stress and skin aging.

WO03074654A2 discloses the use of dsRNA as a method or reagent for modulating gene expression, inter alia, for therapeutic and diagnostic applications.

US5877160 discloses a method of reducing androgen-mediated hair loss by reducing the level of protein-bound 5-alphadihydrotestosterone in scalp tissue without significantly affecting testosterone metabolism in other tissues, exposing the scalp cells to an effective amount of an oligomer that interacts with a gene that an androgenic receptor, 5-alpha-reductase or its transcription product, or a target sequence, which directly connects "upstream" to the transcription start sequence of the corresponding gene and thus reduces or prevents the expression of the androgenic receptor or the 5-alpha reductase.

WO9418835 discloses a method for reducing androgen-mediated hair loss by reducing the level of protein-bound 5-alphadihydrotestosterone in scalp tissue without significantly affecting testosterone metabolism in other tissues, exposing the scalp cells to an effective amount of an oligomer or oligomers that are associated with a gene interact that an androgenic receptor, 5-alpha reductase or its transcription product, or a target sequence which directly follows upstream of the transcription start sequence of the corresponding gene and thus reduces or prevents the expression of the androgenic receptor or the 5-alpha-reductase.

US5994319 discloses more specific oligonucleotides with a nucleotide sequence that is complementary to at least a portion of the pre-mRNA transcript or the transcript of matured mRNA of human 5-alpha reductase type I or II, wherein the oligonucleotide can hybridize with the mRNA transcript.

US5556956 also describes more about the treatment of hair loss using antisense oligodeoxyribonucleotides.

The document US20030211065A1 discloses a therapeutic agent for the diagnosis and / or therapy of hair loss (alopecia) and other hair growth-associated indications containing a therapeutic agent which modulates the activity of comeodesmosin at the protein and / or gene level, inter alia through the use of oligoribonucleotides.

The document WO03101376A2 discloses the topical application of at least one double-stranded RNA oligonucleotide for cosmic or therapeutic treatment; for example psoriasis.

The document WO03070197A2 discloses the production and use of short interfering nucleic acid molecules, for example for the treatment and diagnosis of diabetes-related nephropathy, which down-regulate the expression of the transforming growth factor beta receptor.

The document WO03074654A2 discloses methods and reagents for modulating gene expression for, inter alia, therapeutic and diagnostic applications which contain small interfering nucleic acid molecules (siRNA) for the treatment of any diseases or indications which can be treated by modulating gene expression in cells, tissues or in the organism.

US20030157030A1 relates to methods and respiratory compositions for attenuating the expression of target genes in vivo using small interfering RNAs; in particular for changing the growth, survival or differentiation of cells for therapeutic and cosmetic applications using pulmonary or nasal application forms.

The document DE 10148393 discloses a cosmetic cleaning agent which is a combination of packaging and application agents and a liquid cleaning preparation and is converted into a stable foam with the aid of the applicator.

All this shows no way to formulations which are suitable for the treatment and prophylaxis of the reduced (hair loss, hair miniaturization) or the undesirable (hypertrichosis) growth of hair of the scalp or the body, in that the hair growth is modulated in the desired manner by the oligoribonucleotides according to the invention. Based on this, the task was to provide preparations that have this effect.

Known hair treatment agents often have disadvantages. Often their effects are unsatisfactory or they are not harmless to health, especially when used continuously.

Topical cosmetic preparations which influence the hair growth in a desired inducing or inhibiting manner are therefore particularly desirable.

An object of the present invention was to provide compositions which enable effective treatment and prophylaxis of the reduced (hair loss, hair miniaturization) or undesirable (hypertrichosis) growth of hair and in particular the strengthening of the hair without showing the disadvantages of the prior art.

Another object of the invention was to provide better means for influencing hair growth.

It has not been foreseen for the person skilled in the art that oligoribonucleotides, which induce the breakdown of the mRNA of structures, influence the hair cycle in a stimulating or inhibiting manner, the structures being proteins and enzymes and the structures being members of the<ul id="ul0001" list-style="none" compact="compact"><li>(a) Transfoming Growth Factor beta superfamily (TGFbeta) and their receptors (TGFbetaR),</li><li>(b) structures that reduce hair growth,</li><li>(c) represent structures that promote hair growth,</li></ul> remedy the shortcomings of the prior art.

This object is achieved by oligoribonucleotides which are able to inhibit the expression of the genes of hair cycle regulating proteins or enzymes.

The invention relates to the use of oligoribonucleotides which induce the breakdown of the mRNA of proteins and enzymes which influence the hair cycle in a stimulating or inhibiting manner for the production of cosmetic or dermatological preparations for the treatment and prophylaxis of the reduced (hair loss, hair miniaturization ) or the undesired (hypertrichosis) growth of hair on the scalp or body, such as those associated with age-related changes in hair growth.

The topical application of double-stranded RNA molecules (RNAi) in cosmetic formulations can achieve the new formation of scalp hairs combined with an extension of the growth phase of the hair follicles (hair strengthening) as well as the reverse effect (hair miniaturization). This is made possible in particular by the selective inhibition of the translation of the TGFbeta-1, the androgen receptor, the sonic hedgehog gene or the gene of the insulin-like growth factor 1 using specific and efficiently acting siRNA molecules. This enables a targeted influence on the hair cycle and allows targeted prophylaxis or therapy of undesirable hair conditions such as hair loss / thin hair or undesirably strong hair growth / strong hair.

It was further found that it is preferred if the structures of the TGFbeta factors from the group<dl id="dl0001" compact="compact"><dt>TGFbeta-1</dt><dd>NM000660 P03956 (EC 3.4.24.7)</dd><dt>TGFbeta-2</dt><dd>NM003238</dd><dt>TGFbeta-3</dt><dd>BT007287</dd><dt>TGFbeta-R I</dt><dd>XM005591</dd><dt>TGFbeta-R II</dt><dd>BC040499 can be selected.</dd></dl>

The TGFbeta superfamily contains a group of secreted signaling molecules that play a role in cell growth and differentiation and play an important role in regulating the hair cycle. TGFbeta proteins are expressed depending on the hair cycle (Seiberg et al, 1995). The activity of these proteins is responsible for the transfer of the anagen hair follicle to the Catagen / Telogen (Foitzik et al., 2000). Studies in mice that express TGFbeta1 in a regulatable manner showed that an unnatural, constant induction of TGFbeta1 expression causes hair loss. This alopecia can be attributed to a telogen arrest (Liu et al., 2001) and is evident from a greatly increased apoptosis rate of follicular cells. A proliferation-inhibitory TGFbeta1 effect could also be demonstrated in human hair follicles cultivated in vitro (Hoffmann et al., 1996). The exact mechanism underlying the proliteration-inhibitory effect on the hair roots (anagen-catagen transit) has not yet been fully elucidated.

It is further preferred if the structures promoting hair growth are selected from the group of the enzymes which are expressed in the hair follicle and introduce the substrate testosterone into the cell, in particular the androgen receptor (L29496 and N18624) and those oligoribonucleotides which - additionally described by their access numbers (Accession Nummers) from the NCBI database - selected from the group NM_001963 (Homo sapiens epidermal growth factor, beta-urogastrone, EGF, mRNA), NM_005228 (Homo sapiens epidermal growth factor receptor, EGFR, mRNA), NM_033164 (Homo sapiens fibroblast growth factor 8, androgen-induced, FGF8), NM_004464 (Homo sapiens fibroblast growth factor 5, FGF5, transcript variant 1, mRNA), NM_033143 Homo sapiens fibroblast growth factor 5, FGF5, transcript variant 2, mRNA), NM_003182 (Homo sapiens tachykinin, precursor I (substance K, substance P, neuroldnin 1, neurokinin 2, neuromedin L, neurokinin alpha, neuropeptide K, neuropeptide gamma) (TAC 1), transcript variant beta, mRNA), NM_005605 (Homo sapiens protein phosphatase 3 (formerly 2B), catalytic subunit, gamma isoform (calcineurin A gamma) (PPP3CC), mRNA), BC028049 (Homo sapiens protein phosphatase 3 (formerly 2B), catalytic subunit, beta isoform (calcineurin A beta), mRNA), BC025714 (Homo sapiens protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform (calcineurin A alpha), mRNA), BC027913 (Homo sapiens protein phosphatase 3 (formerly 2B), regulatory subunit B, 19kDa, alpha isoform (calcineurin B, type I), mRNA), BC030595 (Homo sapiens protein phosphatase 3 (formerly 2B), regulatory subunit B, 19kDa, beta isoform (calcineurin B, type II), mRNA), BC045628 (Homo sapiens nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1, mRNA), BC001971 (Homo sapiens cyclin-dependent kinase inhibitor 1B (p27, Kip1), mRNA), BC008678 (Homo sapiens interleukin 1, beta, mRNA), M84426 (Homo sapiens substance P receptor (short form) mRNA), M84425 (Homo sapiens substance P receptor (long form) mRNA), BC028145 (Homo sapiens, Similar to thrombospondin 1), BC028148 (Homo sapiens tumor necrosis factor (TNF superfamily, member 2, mRNA), BC002379 (Homo sapiens MAD, mothers against decapentaplegic homolog 4 (Drosophila), mRNA), BC027478 (Homo sapiens thrombospondin repeat containing 1, mRNA), BC022367 (Homo sapiens thrombospondin, type I, domain 2, mRNA) .

It is further preferred if the hair growth-reducing structures are selected from the group of the Sonic Hedgehog Protein (L38518), the insulin-like growth factor 1 (X00173) and - additionally described by their accession numbers (Accession Numbers) from the NCBI database - from the group P13611 (Versican core protein precursor, Large fibroblast proteoglycan), NP_000566 (interleukin 1, alpha proprotein; preinterleukin 1 alpha; hematopoietin-1 [Homo sapiens], AJ277165 (Homo sapiens mRNA for hairless protein (putative single zinc finger transcription factor protein, responsible for autosomal recessive universal congenital alopecia, HR gene)), AY217036 (Homo sapiens BCL2-associated X protein (BAX) genes).

The Sonic Hedgehog Protein (L38518) and the insulin-like growth factor 1 (X00173) are signaling proteins that promote hair growth and whose inhibition is used for hair miniaturization, for example for deodorant preparations.

It is further preferred if in such oligoribonucleotides their target sequence or sequences represent the coding regions (cDNA) of the respective genes, particularly preferably those regions of the coding regions which are 50 to 100 nucleotides downstream of the start codon.

It is further preferred if it is a matter of double-stranded RNA molecules (dsRNAs) which are homologous to the sequence of the target gene, or a section thereof, that is to say match the target gene in terms of sense and antisense strand.

It is further preferred if the dsRNA is not completely identical to the target sequence, preferably in such a way that, based on a length of 20 base pairs, preferably no more than 0 to 2, particularly preferably 0 to 1 and very particularly preferably no deviations from the target sequence occur . This means that a maximum of 0 to 2 and in particular a maximum of 0 to 1 base pairs are exchanged for other base pairs.

It is further preferred if the oligoribonucleotides have a length of 15 to 49 nucleotides, preferably 17 to 30, particularly preferably 19 to 25 and very particularly preferably 20 to 23 nucleotides.

It is further preferred if the RNA duplexes have smooth (blunt ends) or projecting ends (sticky ends).

It is further preferred if the oligoribonucleotides are double-stranded and have an overhang of 1 to 6, preferably 1 or 2, nucleotides at the 3 ′ end of each strand.

It is further preferred if the oligoribonucleotides according to the invention are homologous to such a section of the target gene and in particular the corresponding double-stranded cDNA, the sense strand of which is on the 5 'side by two adenosine residues (A) and the 3' side by two thymidine residues (T) a guanosine (G) and a cytosine residue (C) or a thymidine and a cytidine residue (C) is limited.

It is further preferred if they are integrated into expression vectors, in particular those which bring about an expression of the oligoribonucleotides in mammalian cells.

It is further preferred if such oligoribonucleotides are chemically modified at the level of the sugar residues, the nucleobases, the phosphate groups and / or the skeleton located between them.

It is further preferred if one or more phosphate groups are replaced by phosphorothioate, methylphosphonate and / or phosphoramidate groups.

It is further preferred if oligoribonucleotides according to the invention are characterized by the replacement of one or more ribose residues of the oligoribonucleotide by morpholine rings (morpholine oligoribonucleotides) or by amino acids (peptide oligoribonucleotides).

It is further preferred if their ribose residues are modified by amino residues, such as NH2, fluorine, alkyl or O-alkyl residues, such as OCH3.

It is further preferred if they contain α-nucleosides.

It is further preferred if used in encapsulated form, for example encapsulated in liposomes or stabilized by the addition of cyclodextrins.

It is further preferred if oligoribonucleotides according to the invention inhibit the expression of the respective target gene in comparison to untreated cells by at least 40%, preferably by at least 60%, particularly preferably by at least 80% and very particularly preferably by at least 85%.

It is further preferred if oligoribonucleotides according to the invention and their salts are used as an effective component of pharmaceutical and cosmetic compositions, in particular those for topical use.

The invention also includes cosmetic and / or dermatological preparations containing oligoribonucleotides according to the invention and preparations additionally containing one or more oligoribonucleotides which inhibit the expression of the protein kinase PKR and thus counteract non-specific inhibition of translation.

It is further preferred if preparations according to the invention contain 1 to 5 and in particular 1 to 3 different oligoribonucleotides.

The invention also encompasses the use of oligoribonucleiotides according to the invention in preparations for the treatment and prophylaxis of age-related and environmental-related degenerative and deficient manifestations of the hair follicles, the skin and skin appendages, such as glands, in particular the symptoms described in more detail in the description.

The invention also includes the use of preparations according to the invention for protecting against hair loss, hair follicle miniaturization, thinning hair, signs of depigmentation of the hair, dystrophic changes in the hair root, in particular the hair on the head, and for the treatment and prophylaxis of hypertrichosis and undesirable growth of body hair, in particular on the Legs, armpits and beard area.

Finally, the invention also includes the use of oligoribonucleotides according to the invention in products containing deodorants or antiperspirants for use under the armpit

In addition to the oligoribonucleotides mentioned, physiologically tolerable salts of such oligoribonucleotides are also suitable according to the invention. In the following, for the sake of simplicity, the term oligoribonucleotide is used both for the oligoribonucleotides themselves and for their salts, unless stated otherwise. The term oligoribonucleotide also includes modified oligoribonucleotides.

The numbers given are the access numbers from the National Institutes of Health's NCBI (National Center for Biotechnology Information) database.

However, the invention also relates to longer nucleotide fragments, such as, for example, dsRNAs, which correspond in length to the respective target mRNAs or cDNAs. These can, for example, be converted into fragments of a length of 21 to 23 nucleotides using soluble Drosophila embryo extract (cf. WO01 / 75164). Long-chain dsRNA is also broken down into short pieces intracellularly. However, the direct use of long-chain dsRNA is generally not preferred since it can cause non-specific inhibition of translation in mammalian cells.

The RNA duplexes according to the invention can have blunt ends or sticky ends. Double-stranded oligoribonucleotides have been found to be particularly effective which have an overhang of 1 to 6, preferably 1 or 2, nucleotides at the 3 'end of each strand. The protruding nucleotides are preferably 2'-deoxynucleotides, particularly preferably 2'-deoxythymidine residues. By using the 2'-deoxynucleotides, the costs of RNA synthesis can be reduced and the resistance of the RNA to the nuclease degradation can be increased. The protruding nucleotides need not necessarily be the nucleotides homologous to the target sequence and are therefore not taken into account in the deviations from the target sequence defined above. However, preferred are oligoribonucleotides with short supernatants, in particular of 2 nucleotides, in which the protruding nucleotides of the antisense strand of the dsRNA are complementary to the target sequence.

Oligoribonucleotides which are homologous to such a section of the target gene and in particular the corresponding double-stranded cDNA, the sense strand of which has 5 'sides by two adenosine residues (A) and 3' sides by two thymidine residues (T), have proven particularly effective. a guanosine (G) and a cytosine residue (C) or a thymidine and a cytidine residue (C) is limited. The by AA and TT, AA and GC or The section delimited by AA and TC preferably has a length of 19 to 21, in particular 19 nucleotides and accordingly has the general form AA (N19-21) TT, AA (N19-21) GC or AA (N19-21) TC, where N stands for a nucleotide. Oligoribonucleotides which are complementary to a section of the target gene or the corresponding double-stranded cDNA which has the general form AA (N19) to AA (N21) are further preferred. Here, oligoribonucleotides that are homologous to the N19-21 fragment of the regions mentioned are particularly preferred. The particularly preferred oligoribonucleotides thus have a length of 19 to 21 base pairs, the single strands forming these oligoribonucleotides preferably having two additional 2'-deoxynucleotides on the 3 'side, in particular two 2'-deoxythymidine residues, so that the dsRNA 19 to 21 base pairs and comprises two protruding 2'-deoxynucleotides per strand.

If the target gene does not contain any region of the form AA (N19-21), regions of the form NA (N19-21) or any fragment of the form N19-21 are searched for. N19-21 fragments which are delimited, for example, by AA and TT are preferred, but in principle all dsRNA fragments which are homologous to the target sequence are suitable according to the invention.

FIG. 1 shows the single-stranded cDNA of the growth factor TGFbeta-1 (SEQ ID NO 1) in which all fragments of the form AA-N19-TC and AA-N19-GC are optically highlighted. These fragments (targeted region) are shown in FIG. 2 together with the corresponding homologous (senseRNA) and complementary (antisenseRNA) RNA single strands. Single-stranded RNAs are shown which are modified on the 3 ′ side by two deoxythymidine residues (dt). The hybridization of two complementary single-stranded RNAs results in dsRNA with protruding 3 'ends, which are each formed by two 2'-deoxythymidine residues.

The gene of the growth factor TGFbeta-1 is one of the preferred target genes for the oligoribonucleotides according to the invention. Accordingly, oligoribonucleotides which are homologous to the double-stranded sequence derived from SEQ ID NO 1, sections thereof and in particular to the double-stranded sequences derived from the sections highlighted in FIG. 1 are particularly preferred according to the invention (see FIG. 2). The double-stranded sequence derived from SEQ ID NO 1 is understood to mean the sequence which is formed from SEQ ID NO 1 and the strand which is complementary thereto. The other information is to be understood accordingly.

FIG. 3 shows the single-stranded cDNA of the Sonic Hedgehog gene (SEQ ID NO 20). Here too, a preferred sequence region, ie a sequence region with a length of 19 nucleotides, which is flanked by AA and TT or AA and TC, is emphasized. Oligoribonucleotides which are homologous to the double-stranded sequence derived from SEQ ID NO 20, sections thereof and in particular to the double-stranded sequence which is derived from the region highlighted in FIG. 3 are likewise preferred according to the invention.

FIG. 4 shows the single-stranded cDNA of the androgen receptor (SEQ ID NO 21), preferred sequence regions, ie a sequence region with a length of 19 nucleotides, which is flanked by AA and TT or AA and TC or AA and GC, again marked are. Oligoribonucleotides which are homologous to the double-stranded sequence derived from SEQ ID NO 21, sections thereof and in particular to the double-stranded sequence which is derived from the regions highlighted in FIG. 4 are likewise preferred according to the invention.

FIG. 5 shows the single-stranded cDNA of the insulin-like growth factor 1 (SEQ ID NO 22), preferred sequence regions again being marked. Oligoribonucleotides which are homologous to the double-stranded sequence derived from SEQ ID NO 22, sections thereof and in particular to the double-stranded sequence which is derived from the regions highlighted in FIG. 5 are likewise preferred according to the invention.

The oligoribonucleotides according to the invention could advantageously also be integrated into expression vectors, in particular those which bring about an expression of the oligoribonucleotides in mammalian cells. In this way, a stable inhibition of the expression of the target gene can be achieved even with an intracellular degradation of the oligoribonucleotides, since oligoribonucleotides are constantly supplied by the vector-assisted synthesis. One or more copies of a dsRNA can be integrated into a vector, but also one or more copies of two or more different dsRNAs. Suitable vector systems are described, for example, by Brummelkamp et al., Loc. Cit. Mammalian expression vectors are preferred, in particular those which form a polymerase III H1 RNA promoter and 5 to 9 so-called loops which are formed from a dsRNA according to the invention and a sequence of the same length, which is reversely complementary to the dsRNA according to the invention and serves as a spacer , and contain a termination signal of 5 successive thymidine residues. The vectors thus contain 5 to 9 copies of the respective dsRNA molecule. These can be dsRNAs that are specific for 1 target gene or dsRNAs that are specific for several different target genes.

The oligoribonucleotides according to the invention can be in the form of the unmodified oligoribonucleotides. However, they are preferably oligoribonucleotides which are chemically modified at the level of the sugar residues, the nucleobases, the phosphate groups and / or the skeleton located between them, in order, for example, to increase the stability of the oligoribonucleotides in cosmetic or dermatological preparations and / or in the skin , e.g. against nucleolytic degradation, in order to improve the penetration of the oligoribonucleotides into the skin and the cell, to have a favorable influence on the effectiveness of the oligoribonucleotides and / or to improve the affinity for the sequence sections to be hybridized.

Oligoribonucleotides in which one or more phosphate groups are replaced by phosphorothioate, methylphosphonate and / or phosphoramidate groups, such as, for example, N3 '→ P5'-phosphoramidate groups, are preferred. Oligoribonucleotides in which phosphate groups are replaced by phosphothioate groups are particularly preferred. One or more of the phosphate groups of the oligoribonucleotide can be modified. In the case of a partial modification, terminal groups are preferably modified, but oligoribonucleotides in which all the phosphate groups have been modified are particularly preferred. This also applies mutatis mutandis to the modifications described below.

Preferred sugar modifications include the replacement of one or more ribose residues of the oligoribonucleotide with morpholine rings (morpholine oligoribonucleotides) or with amino acids (peptide oligoribonucleotides). All of the ribose residues of the oligoribonucleotide are preferably replaced by amino acid residues and in particular morpholine residues.<chemistry id="chem0001" num="0001"><img file="EP1598421A2_D0001.tif" /></chemistry>

Morpholine oligoribonucleotides in which the morpholine residues are linked to one another via sulfonyl or preferably phosphoryl groups are particularly preferred, as can be seen in formula 1 or 2:<ul id="ul0002" list-style="none"><li>B represents a modified or unmodified purine or pyrimidine base, preferably adenine, cytosine, guanine, or uracil,</li><li>X represents O or S, preferably O,</li><li>Y represents O or N-CH3, preferably O,</li><li>Z stands for alkyl, O-alkyl, S-alkyl, NH2, NH (alkyl), NH (O-alkyl), N (alkyl) 2, N (alkyl) (O-alkyl), preferably N (alkyl) 2, where alkyl is linear or branched alkyl groups having 1 to 6, preferably 1 to 3 and particularly preferably 1 or 2 carbon atoms.</li></ul>

Formulas 1 and 2 each represent only a section of an oligoribonucleotide chain.

Morpholine oligoribonucleotides in which the morpholine residues are connected to one another via phosphoryl groups are very particularly preferred, as shown in formula 2, in which X is O, Y is O and Z is N (CH3) 2.

Furthermore, the ribose residues can be modified by amino residues, such as NH2, fluorine, alkyl or O-alkyl residues, such as OCH3, 2'-modified oligoribonucleotides being particularly preferred. Exemplary modifications are 2'-fluoro, 2'-alkyl, 2'-O-alkyl, 2'-O-methoxyethyl modifications, 5'-palmitate derivatives and 2'-O-methylribonucleotides.

The modification of the nucleotides of dsRNA counteracts an activation of the protein kinase PKR in the cell, which is dependent on double-stranded RNA. This avoids unspecific inhibition of translation. The substitution of at least one 2'-hydroxyl group of the nucleotides of the dsRNA by a 2'-amino or a 2'-methyl group is particularly suitable for this purpose. Furthermore, at least one nucleotide in at least one strand of the dsRNA can be replaced by a so-called "locked nucleotide" which contains a chemically modified sugar ring. A preferred modification of the sugar ring is a 2'-O, 4'-C-methylene bridge. dsRNA containing several "locked nucleotides" is preferred.

Unless stated otherwise, alkyl here preferably represents linear, branched or cyclic alkyl groups having 1 to 30, preferably 1 to 20, particularly preferably 1 to 10 and very particularly preferably 1 to 6 carbon atoms. Branched and cyclic radicals naturally have at least 3 carbon atoms, cyclic radicals having at least 5 and in particular at least 6 carbon atoms being preferred.

Oligoribonucleotides containing α-nucleosides can also be used.

Suitable base modifications are described, for example, in US Pat. No. 6,187,578 and WO 99/53101, to which reference is hereby expressly made. A modification of one or more pyrimidines in position 5 with I, Br, Cl, NH3 and N3 has proven to be advantageous.

The synthesis of modified and unmodified oligoribonucleotides and other suitable modification options are described in the literature. In addition, the production of modified and unmodified oligoribonucleotides is now also offered as a service by numerous companies, for example by Dharmacon, 1376 Miners Drive # 101, Lafayette, CO 80026, USA, Xeragon Inc., Genset Oligos and Ambion. The production of oligoribonucleotides is also described in US Pat. No. 5,986,084.

To increase stability and / or penetration, the oligoribonucleotides can also be used in encapsulated form, for example encapsulated in liposomes. They can also be stabilized by adding cyclodextrins.

Cyclodextrins are also known as cycloamyloses and cycloglucans. The cyclodextrins are cyclic oligosaccharides consisting of α-1,4 linked glucose units. As a rule, six to eight glucose building blocks (α-, □ - or γ-cyclodextrin) are linked together. Cyclodextrins are obtained when Bacillus macerans acts on starch. They have a hydrophobic interior and a hydrophilic exterior. According to the invention, both the cyclodextrins themselves, in particular α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, as well as derivatives thereof are suitable.

According to the invention, the cyclodextrin (s) are preferably used in cosmetic and dermatological compositions in a concentration of 0.0005 to 20.0% by weight, in particular 0.01 to 10% by weight and particularly preferably in a concentration of 0.1 to 5.0% by weight.

According to the invention, it is advantageous to use native, polar and / or nonpolar substituted cyclodextrins. These preferably but not exclusively include methyl-, in particular random-methyl-β-cyclodextrin, ethyl- and hydroxypropyl-cyclodextrins, for example hydroxypropyl- □ -cyclodextrin and hydroxypropyl- □ -cyclodextrin. The cyclodextrin species which are particularly preferred according to the invention are γ-cyclodextrin and hydroxypropyl-β-cylcodextrin.

Liposomes can be prepared in a manner known per se using natural phospholipids, such as, for example, phosphatidylcholine from eggs, soybeans, etc., or synthetic phospholipids (cf. G. Betageri (editor), "Liposome Drug Delivery Systems", Lancaster Techonomic Publishing Company 1993; Gregoriadis (Editor), "Liposome Technology", CRC Press). Preferred methods and materials for the production of liposomes are described in WO 99/24018.

Double-stranded oligoribonucleotides can also be modified to counter dissociation into the single strands, for example by one or more covalent, coordinative or ionic bonds. However, oligoribonucleotides without such modifications are preferred.

The nucleotides in the RNA molecules can also include "non-standard" nucleotides, such as non-naturally occurring nucleotides or deoxyribonucleotides.

According to the invention, those oligoribonucleotides are preferred which inhibit the expression of the respective target gene by at least 40%, preferably by at least 60%, particularly preferably by at least 80% and very particularly preferably by at least 85% compared to untreated cells. If necessary, the expression of the target gene is first induced in the cells in a suitable manner to measure the inhibition. To determine the effectiveness of the oligoribonucleotides according to the invention, tumor cells of the HeLaS3 line are preferably used. The oligoribonucleotides are introduced into the cells and then, if necessary after induction of the expression of the target gene, the expression rate of the target gene in these cells is measured and compared with that found in cells that have not been transfected with the respective oligoribonucleotide. The exact conditions for measuring the inhibition can be found in Example 1.

The oligoribonucleotides according to the invention and their salts are particularly suitable as an effective component of pharmaceutical and cosmetic compositions, in particular those for topical use.

It has surprisingly been found that after the compositions have been applied to the scalp or skin, the oligoribonucleotides inhibit the expression of the genes which are responsible for the inhibition or stimulation of the growth phase of the hair follicle and thus increase or decrease the hair growth without side effects and in this way an effective treatment and prophylaxis of the reduced (hair loss, Hair miniaturization) or the undesirable (hypertrichosis) growth of hair of the scalp or body without showing the disadvantages of the prior art. It is believed that this effect is due to the fact that the oligoribonucleotides according to the invention are absorbed by the cells of the hair follicle and induce the degradation of the mRNAs of the genes mentioned by RNAi intracellularly, details of the mechanism of this reaction cascade not yet being known. The oligoribonucleotides are therefore particularly suitable for initiating the breakdown of mRNA of proteins or enzymes which inhibit or induce hair growth and for inhibiting the expression of proteins or enzymes which inhibit or induce hair growth in the scalp or skin and in particular in hair follicle cells.

The compositions according to the invention can additionally contain one or more oligoribonucleotides which inhibit the expression of the protein kinase PKR and thus counteract non-specific inhibition of translation.

The pharmaceutical or cosmetic compositions according to the invention preferably contain 0.00001 to 10% by weight, particularly preferably 0.0003 to 3% by weight and very particularly preferably 0.01 to 1.0 of the oligoribonucleotide (s) according to the invention, based on the total weight the composition. When using oligorbinonucleotides that are integrated in vectors, the above quantity relates to the mass of the oligoribonucleotides integrated in the vector, the mass of the vector itself is not taken into account.

According to the invention, preference is given to compositions which contain only those oligoribonucleotides which inhibit the expression of one or more of the genes mentioned above, ie of the genes which inhibit or induce the hair cycle and, if appropriate, of the proteinase PKR, and in particular of the preferred genes mentioned. The compositions according to the invention can contain one or preferably more oligoribonucleotides. These can be oligoribonucleotides that inhibit the expression of several different hair cycle inhibiting or inducing proteins or enzymes, but it is also possible to use mixtures of oligoribonucleotides that different sequence regions of the same gene or the same mRNA of a hair cycle inhibiting or inducing protein or enzyme have the objective. Compositions which contain 1 to 5 and in particular 1 to 3 different oligoribonucleotides are preferred. Mixtures of oligoribonucleotides which, in addition to the hair cycle-inhibiting or inducing proteins or enzymes mentioned and possibly the proteinase PKR, non-specifically inhibit or induce the activity of a large number of other skin or hair proteins are undesirable since practically no control of side effects is possible. Under skin or Hair proteins are understood to be those proteins which are expressed in the skin or in the hair follicle. Compositions which contain one or more oligoribonucleotides which inhibit the expression of one or more TGFbeta factors are very particularly preferred.

Compositions which each contain at least one oligoribonucleotide which is directed against a hair growth-inhibiting steroid-binding or catalyzing protein, an androgen receptor or a 5-alpha-reductase are furthermore particularly preferred.

Compositions are also particularly preferred which each contain at least one oligoribonucleotide which is directed against a cellular signaling molecule which induces hair growth, the sonic hedgehog protein.

Compositions which each contain at least one oligoribonucleotide which is directed against a growth factor inducing hair growth, an insulin-like growth factor, are furthermore particularly preferred.

The oligoribonucleotides and compositions are suitable for the treatment and prophylaxis of age-related and environmental-related degenerative and deficient manifestations of the hair follicles, the skin and appendages, such as glands, in particular the symptoms described above. They are suitable for the cosmetic and therapeutic treatment of degenerative conditions of the hair follicle, which are caused by endogenous and exogenous factors, such as circulatory disorders, reduced energy supply to the hair root and, in particular, hormonal influences. The compositions according to the invention can prevent damage to the hair follicle and permanently remove existing damage and without the risk of side effects. For example, the method described in WO02 / 053773 can be used to determine the effectiveness of the oligoribonucleotides according to the invention.

The oligoribonucleotides and compositions are suitable for the prophylaxis and treatment of hair loss, hair follicle miniaturization, thinning hair, signs of depigmentation of the hair, dystrophic changes in the hair root, and for the treatment and prophylaxis of hypertrichosis and undesirable growth of body hair, in particular on the legs, armpits and armpits.

Because of their prophylactic effect, the oligoribonucleotides and compositions according to the invention are also outstandingly suitable for hair, scalp and skin care.

The compositions according to the invention are also suitable for the treatment of the hair follicle deficits caused by reduced nutrient and / or oxygen supply, for example due to age-related reduction in the perifollicular capillary vessels and the capillary loop in the follicular papilla.

The compositions according to the invention are suitable for cosmetic and therapeutic, ie in particular dermatological, use.

Cosmetic skin care is primarily understood to mean that the natural function of the skin or scalp acts as a barrier against environmental influences (e.g. dirt, chemicals, microorganisms) and against the loss of the body's own substances (e.g. water, natural fats) , Electrolytes) is strengthened or restored. If this function is disturbed, there may be an increased absorption of toxic or allergenic substances or an infestation of microorganisms and, as a result, toxic or allergic skin reactions. The aim of skin care is also to compensate for the loss of fat and water in the skin caused by daily washing. This is particularly important when the natural regeneration ability is insufficient. In addition, skin care products are intended to protect against environmental influences, especially sun and wind.

For cosmetic use, the compositions according to the invention therefore preferably contain those components which are suitable for the purposes mentioned. Such substances are known per se to the person skilled in the art. For example, one or more oligoribonucleotides can be incorporated into conventional cosmetic and dermatological preparations, which can be in various forms.

For use, the preparations according to the invention are preferably applied directly to the scalp or body skin, in the manner known for such agents, for example twice a day.

Solutions, gels, ointments, suspensions or emulsions such as creams or lotions containing the active compounds according to the invention are suitable, for example.

According to a particularly preferred embodiment, the compositions according to the invention for cosmetic use are present as hair treatment agents, in particular as those which remain in the hair or are used with a longer contact time. In this way, the active ingredients get into or on the scalp or in the area of ​​the hair roots. Hair treatment agents that only come into contact with the skin or hair for a short time, e.g. Shampoos, for example, can have higher amounts of active ingredient.

Hair treatment agents are, for example, shampoos, hair care products such as hair lotions, hairdressing aids, hair rinses, hair treatments, spa packs, hair setting agents such as foam set, hair spray, hair lacquer, hair shaping agents and hair colorants.

It is further particularly preferred to use the described oligoribonucleotides in preparations that are not primarily intended for the treatment of the hair. These can be all conceivable cosmetic and / or dermatological preparations, for example deodorant or perspirant preparations (deodorant or AT preparations), advantageously those for use under the armpit. In these, hair growth-reducing oligoribonucleotides can be provided for use simultaneously with the AT or deodorant active ingredients. In addition to the deodorant / AT effect, the use of such preparations then leads to a reduction in hair growth, for example shaved armpits. Such preparations are therefore also suitable for reducing the shaving frequency or increasing the sustainability of the shaving. According to the use according to the invention, the cosmetic deodorants can be in the form of aerosols, that is to say from aerosol containers, squeeze bottles or preparations sprayable by a pump device, or in the form of liquid compositions which can be applied by means of roll-on devices, as deodorant sticks and deodorant sticks Form of W / O or O / W emulsions that can be applied from normal bottles and containers, eg creams or lotions. Furthermore, the cosmetic deodorants can advantageously be in the form of deodorant tinctures, deodorant intimate cleansers, deodorant shampoos, deodorant shower or bath preparations, deodorant powders or deodorant powder sprays.

The same applies to skin care preparations which are suitable for use on the face or on the legs or on other parts of the body on which hair growth is considered to be disruptive. According to a particularly preferred embodiment, the compositions according to the invention for cosmetic use are in the form of an emulsion, for example in the form of a cream, a lotion, or a cosmetic milk. In addition to the oligoribonucleotides mentioned, these contain further components such as, for example Fats, oils, waxes and / or other fat bodies, as well as water and one or more emulsifiers, as are usually used for such a type of formulation.

Emulsions usually contain a lipid or oil phase, an aqueous phase and preferably also one or more emulsifiers. Compositions which also contain one or more hydrocolloids are particularly preferred.

The compositions according to the invention preferably contain 0.001 to 35% by weight, particularly preferably 2 to 15% by weight of emulsifier, 0.001 to 45% by weight, particularly preferably 10 to 25% by weight of lipid and 10 to 95% by weight , particularly preferably 60 to 90 wt .-% water.

The omission of a single component affects the unique properties of the overall composition. Therefore, all of the stated components of the preparations according to the invention are absolutely necessary in order to carry out the invention.

The cosmetic preparations according to the invention can contain cosmetic auxiliaries as are usually used in such preparations, for example preservatives, bactericides, deodorising substances, antiperspirants, insect repellents, vitamins, agents for preventing foaming, dyes. Pigments with a coloring effect, thickeners, softening substances, moisturizing and / or moisturizing substances, fats, oils, waxes or other common components of a cosmetic formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives, antioxidants and especially UV -Absorber.

Preparations according to the invention can also advantageously contain substances which absorb UV radiation in the UVB range, the total amount of filter substances being, for example, 0.1% by weight to 30% by weight, preferably 0.5 to 10% by weight. , in particular 1.0 to 6.0% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations which protect the hair or the skin from the entire range of ultraviolet radiation. They can also serve as a sunscreen for the hair.

Advantageous UV-A filter substances for the purposes of the present invention are dibenzoylmethane derivatives, in particular 4- (tert-butyl) -4'-methoxydibenzoylmethane (CAS No. 70356-09-1), which is available from Givaudan under the Parsol® 1789 brand and is sold by Merck under the trade name Eusolex® 9020.

The preparations according to the invention advantageously contain substances which absorb UV radiation in the UV-A and / or UV-B range, the total amount of filter substances, for. B. 0.1 wt .-% to 30 wt .-%, preferably 0.5 to 20 wt .-%, in particular 1.0 to 15.0 wt .-%, based on the total weight of the preparations to cosmetic To provide preparations that protect the hair or skin from the entire range of ultraviolet radiation. They can also serve as sunscreens for the hair or skin.

Other advantageous UV-A filter substances are the phenylene-1,4-bis (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid<chemistry id="chem0002" num="0002"><img file="EP1598421A2_D0002.tif" /></chemistry> and their salts, especially the corresponding sodium, potassium or trielhanolammonium salts, in particular the phenylene-1,4-bis (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid bis-sodium salt<chemistry id="chem0003" num="0003"><img file="EP1598421A2_D0003.tif" /></chemistry> with the INCI name bisimidazylate, which is available, for example, from Haarmann &amp; Reimer under the trade name Neo Heliopan AP.

Also advantageous are the 1,4-di (2-oxo-10-sulfo-3-bornylidenemethyl) benzene and its salts (especially the corresponding 10-sulfato compounds, especially the corresponding sodium, potassium or triethanolammonium salt) , which is also called benzene-1,4-di (2-oxo-3-bornylidenemethyl-10-sulfonic acid) and is characterized by the following structure:<chemistry id="chem0004" num="0004"><img file="EP1598421A2_D0004.tif" /></chemistry>

Advantageous UV filter substances in the sense of the present invention are also so-called broadband filters, ie filter substances that absorb both UV-A and UV-B radiation.

Advantageous broadband filters or UV-B filter substances are, for example, bis-resorcinyltriazine derivatives with the following structure:<chemistry id="chem0005" num="0005"><img file="EP1598421A2_D0005.tif" /></chemistry> where R¹, R² and R³ are independently selected from the group of branched and unbranched alkyl groups having 1 to 10 carbon atoms or a single hydrogen atom. Particularly preferred are 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (INCI: Aniso triazine ), which is available under the trade name Tinosorb® S from CIBA-Chemicals GmbH, and the 4,4 ', 4 "- (1,3,5-triazine-2,4,6-triyltriimino) -tris-benzoic acid- tris (2-ethylhexyl ester), synonymous: 2,4,6-tris [anilino- (p-carbo-2'-ethyl-1'-hexyloxy)] - 1,3,5-triazine (INCI: Octyl Triazone), which is sold by BASF Aktiengesellschaft under the trade name UVINUL® T 150.

Also other UV filter substances, which the structural motif<chemistry id="chem0006" num="0006"><img file="EP1598421A2_D0006.tif" /></chemistry> are advantageous UV filter substances for the purposes of the present invention, for example the s-triazine derivatives described in European patent application EP 570 838 A1, the chemical structure of which is given by the generic formula<chemistry id="chem0007" num="0007"><img file="EP1598421A2_D0007.tif" /></chemistry> is reproduced, whereby<dl id="dl0002"><dt>R</dt><dd>a branched or unbranched C₁-C₁₈-Alkyl radical, a C₅-C₁₂-Cycloalkyl radical, optionally substituted with one or more C₁-C₄Represents alkyl groups,</dd><dt>X</dt><dd>represents an oxygen atom or an NH group,</dd><dt>R₁</dt><dd>a branched or unbranched C₁-C₁₈-Alkyl radical, a C₅-C₁₂Cycloalkylrest, optionally substituted with one or more C₁-C₄- Alkyl groups, or a hydrogen atom, an alkali metal atom, an ammonium group or a group of the formula<chemistry id="chem0008" num="0008"><img file="EP1598421A2_D0008.tif" /></chemistry>    means in which A is a branched or unbranched C₁-C₁₈-Alkyl radical, a C₅-C₁₂-Cycloalkyl- or aryl radical, optionally substituted with one or more C.₁-C₄- alkyl groups, R₃  represents a hydrogen atom or a methyl group, n represents a number from 1 to 10,</dd><dt>R₂</dt><dd>a branched or unbranched C₁-C₁₈-Alkyl radical, a C₅-C₁₂Cycloalkylrest, optionally substituted with one or more C₁-C₄Represents alkyl groups when X represents the NH group, and a branched or unbranched C₁-C₁₈-Alkyl radical, a C₅-C₁₂Cycloalkylrest, optionally substituted with one or more C₁-C₄- Alkyl groups, or a hydrogen atom, an alkali metal atom, an ammonium group or a group of the formula<chemistry id="chem0009" num="0009"><img file="EP1598421A2_D0009.tif" /></chemistry> means in which A is a branched or unbranched C₁-C₁₈-Alkyl radical, a C₅-C₁₂-Cyclo-alkyl or aryl radical, optionally substituted with one or more C.₁-C₄- alkyl groups, R₃  represents a hydrogen atom or a methyl group, n represents a number from 1 to 10,</dd></dl>    when X represents an oxygen atom.

A particularly advantageous UV filter substance in the sense of the present invention is also an asymmetrically substituted s-triazine, the chemical structure of which is represented by the formula<chemistry id="chem0010" num="0010"><img file="EP1598421A2_D0010.tif" /></chemistry> is reproduced, which is also referred to below as dioctylbutylamidotriazon (INCI: dioctylbutamidotriazone) and is available under the trade name UVASORB HEB from Sigma 3V.

The European patent application EP 775 698 also describes bis-resorcinyltriazine derivatives which are to be used advantageously and whose chemical structure is represented by the generic formula<chemistry id="chem0011" num="0011"><img file="EP1598421A2_D0011.tif" /></chemistry> is reproduced, where R₁ , R₂ and A₁ represent various organic residues.

Also advantageous for the purposes of the present invention are 2,4-bis - {[4- (3-sulfonato) -2-hydroxypropyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1, 3,5-triazine sodium salt, the 2,4-bis - {[4- (3- (2-propyloxy) -2-hydroxypropyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) - 1,3,5-triazine, the 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- [4- (2-methoxyethylcarboxyl) phenylamino] -1,3,5-triazine, the 2,4-bis - {[4- (3- (2-propyloxy) -2-hydroxypropyloxy) -2-hydroxy] phenyl} -6- [4- (2-ethylcarboxyl) phenylamino] -1,3,5-triazine, the 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- (1-methyl-pyrrol-2-yl) - 1,3,5-triazine, the 2,4-bis - {[4-tris (trimethyisiloxysilylpropyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine, the 2,4-bis - {[4- (2 "-methylpropenyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine and the 2,4-bis- { [4- (1 ', 1', 1 ', 3', 5 ', 5', 5'-heptamethylsiloxy-2 "-methyl-propyloxy) -2-hydroxy] phenyl-6- (4-methoxyphenyl) - 1,3,5-triazine.

An advantageous broadband filter for the purposes of the present invention is 2,2'-methylene-bis- (6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol) [INCI : Bisoctyltriazole], which is characterized by the chemical structural formula<chemistry id="chem0012" num="0012"><img file="EP1598421A2_D0012.tif" /></chemistry> and is available under the trade name Tinosorb® M from CIBA-Chemicals GmbH.

Another advantageous broadband filter for the purposes of the present invention is 2- (2H-benzotriazol-2-yl) -4-methyl-6- [2-methyl-3- [1,3,3,3-tetramethyl-1 - [( trimethylsilyl) oxy] disiloxanyl] propyl] phenol (CAS no .: 155633-54-8) with the INCI name Drometrizole Trisiloxane, which is characterized by the chemical structural formula<chemistry id="chem0013" num="0013"><img file="EP1598421A2_D0013.tif" /></chemistry> is marked.

The UV-B filters can be oil-soluble or water-soluble. Advantageous oil-soluble UV-B filter substances are e.g. E.g .: 3-benzylidene camphor derivatives, preferably 3- (4-methylbenzylidene) camphor, 3-benzylidene camphor; 4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester; 2,4,6-trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine; Esters of benzalmalonic acid, preferably 4-methoxybenzalmalonic acid di (2-ethylhexyl) ester; Esters of cinnamic acid, preferably 4-methoxycinnamic acid (2-ethylhexyl) ester, 4-methoxycinnamic acid isopentyl ester; Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone and UV filters bound to polymers.

Advantageous water-soluble UV-B filter substances are e.g. B. salts of 2-phenylbenzimidazole-5-sulfonic acid, such as its sodium, potassium or triethanolammonium salt, and the sulfonic acid itself; Sulfonic acid derivatives of 3-benzylidene camphor, such as. B. 4- (2-oxo-3-bornylidene methyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidene methyl) sulfonic acid and salts thereof.

A further light protection filter substance to be used advantageously according to the invention is ethyl hexyl-2-cyano-3,3-diphenylacrylate (octocrylene), which is available from BASF under the name Uvinul® N 539 and is characterized by the following structure:<chemistry id="chem0014" num="0014"><img file="EP1598421A2_D0014.tif" /></chemistry>

It can also be of considerable advantage to use polymer-bound or polymeric UV filter substances in preparations according to the present invention, in particular those as described in WO-A-92/20690.

Furthermore, it may be advantageous, if appropriate, to incorporate further UV-A and / or UV-B filters into cosmetic or dermatological preparations, for example certain salicylic acid derivatives such as 4-isopropylbenzyl salicylate, 2-ethylhexyl salicylate (= octyl salicylate), homomenthyl salicylate.

The list of UV filters mentioned, which can be used in the sense of the present invention, should of course not be limiting.

Furthermore, the compositions according to the invention can contain antioxidants to protect the cosmetic preparation itself or to protect the constituents of the cosmetic preparations from harmful oxidation processes.

The antioxidants are advantageously chosen from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg 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. α-carotene, β-carotene, lycopene) and their derivatives, aurothioglucose, propylthiouracil and other thiols (e.g. Thioredoxin, 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) as well as sulfoximine compounds (e.g. Buthioninsulfoximines, homocysteine ​​sulfoximine, buthioninsulfones, penta-, hexa-, heptathioninsulfoximine) in very low tolerable dosages (e.g. pmol to µmol / kg), 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, EGTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, alanine diacetic acid, flavonoids, polyphenols, catechins, vitamin C and derivatives (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g. Vitamin E acetate), and coniferyl benzoate of benzoic resin, rutinic acid and its derivatives, ferulic acid and its derivatives, butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguajak resin acid, nordihydroguajaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, eg zinc and its derivatives (zinose and its derivatives, z. ZnSO₄) Selenium and its derivatives (eg selenium methionine), stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide) and the derivatives suitable according to the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active substances.

The amount of the antioxidants (one or more compounds) in the preparations is preferably 0.001 to 30% by weight, particularly preferably 0.05 to 20% by weight, in particular 1 to 10% by weight, based on the total weight of the preparation .

If vitamin A or vitamin A derivatives or carotenes or their derivatives represent the antioxidant or antioxidants, it is advantageous to add their respective concentrations in the range from 0.001 to 10% by weight, based on the total weight of the formulation choose.

If vitamin E and / or its derivatives represent the antioxidant (s), it is advantageous to choose their respective concentrations from the range from 0.001 to 10% by weight, based on the total weight of the formulation.

According to the invention, cosmetic and dermatological preparations advantageously also contain inorganic pigments based on metal oxides and / or other metal compounds which are sparingly soluble or insoluble in water, in particular the oxides of titanium (TiO₂), Zinc (ZnO), iron (e.g. Fe₂O₃), 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. Pigments based on TiO are particularly preferred₂.

For the purposes of the present invention, it is particularly advantageous, although not essential, if the inorganic pigments are present in hydrophobic form, that is to say that they have been treated to be water-repellent on the surface. This surface treatment can consist in that the pigments are provided with a thin hydrophobic layer by methods known per se.

Such a method consists, for example, in that the hydrophobic surface layer according to a direction         n TiO₂+ m (RO)₃ Si-R '-&gt; n TiO₂ (surface) is produced. n and m are stoichiometric parameters to be used at will, R and R 'are the desired organic radicals. For example, hydrophobized pigments shown in analogy to DE-OS 33 14 742 are advantageous.

Favorable TiO₂Pigments are available, for example, under the trade names MT 100 T from TAYCA, M 160 from Kemira and T 805 from Degussa.

Further advantageous active ingredients in the sense of the present invention are natural active ingredients and / or their derivatives, such as. B. alpha-lipoic acid, phytoene, D-biotin, coenzyme Q10, alpha-glucosylrutin, carnitine, carnosine, natural and / or synthetic isoflavonoids, creatine, taurine and / or β-alanine.

Preparations according to the invention can also contain anionic, nonionic and / or amphoteric surfactants, especially if crystalline or microcrystalline solids, for example inorganic micropigments, are to be incorporated into the preparations according to the invention. Surfactants are amphiphilic substances that can dissolve organic, non-polar substances in water.

The hydrophilic portions of a surfactant molecule are mostly polar functional groups, for example -COO^-, -OSO₃^2-, -SO₃^-, while the hydrophobic parts usually represent non-polar hydrocarbon residues. Surfactants are generally classified according to the type and charge of the hydrophilic part of the molecule. There are four groups:

Anionic surfactants generally have carboxylate, sulfate or sulfonate groups as functional groups. In aqueous solution they form negatively charged organic ions in an acidic or neutral environment. Cationic surfactants are characterized almost exclusively by the presence of a quaternary ammonium group. In aqueous solution they form positively charged organic ions in an acidic or neutral environment. Amphoteric surfactants contain both anionic and cationic groups and accordingly behave like anionic or cationic surfactants in aqueous solution depending on the pH. They have a positive charge in a strongly acidic environment and a negative charge in an alkaline environment. In the neutral pH range, however, they are zwitterionic, as the following example should illustrate:         pH = 2 RNH₂⁺CH₂CH₂COOH X^-   (X^- = any anion, for example Cl^-)         pH = 7 RNH₂⁺CH₂CH₂COO^-        pH = 12 RNHCH₂CH₂COO^- B⁺   (B⁺ = any cation, e.g. Na⁺)

Polyether chains are typical of non-ionic surfactants. Non-ionic surfactants do not form ions in an aqueous medium.

Anionic surfactants to be used advantageously are:

Acylamino acids (and their salts), such as (1) acylglutamates, for example sodium acylglutamate, di-TEA-palmitoylaspartate and sodium caprylic / capric glutamate; (2) acyl peptides such as palmitoyl-hydrolyzed milk protein, sodium cocoyl-hydrolyzed soy protein and sodium / potassium cocoyl-hydrolyzed collagen; (3) sarcosinates, for example myristoyl sarcosin, TEA-lauroyl sarcosinate, sodium lauroyl sarcosinate and sodium cocoyl sarcosinate; (4) taurates, e.g. sodium lauroyl taurate and sodium methyl cocoyl taurate; (5) acyl lactylates such as lauroyl lactylate and caproyl lactylate; (6) alaninates;

Carboxylic acids and derivatives such as lauric acid, aluminum stearate, magnesium alkanolate and zinc undecylenate; Ester carboxylic acids, for example calcium stearoyl lactylate, laureth-6 citrate and sodium PEG-4 lauramide carboxylate; Ether carboxylic acids, for example sodium laureth-13 carboxylate and sodium PEG-6 cocamide carboxylate;

Carboxylic acids, ester carboxylic acids and ether carboxylic acids preferably contain 1 to 50 and in particular 2 to 30 carbon atoms.

Phosphoric acid esters and salts such as DEA-oleth-10-phosphate and dilaureth-4-phosphate;

Sulfonic acids and salts, such as (1) acyl isethionates, for example sodium / ammonium cocoyl isethionate; (2) alkylarylsulfonates; (3) alkyl sulfonates, e.g. sodium coconut monoglyceride sulfate, sodium C._12-14 Olefin sulfonate, sodium lauryl sulfoacetate and magnesium PEG-3 cocamide sulfate; (4) sulfosuccinates, for example dioctyl sodium sulfosuccinate, disodium laureth sulfosuccinate, disodium lauryl sulfosuccinate and disodium undecylene amido MEA sulfosuccinate;

Sulfuric acid esters, such as (1) alkyl ether sulfate, for example sodium, ammonium, magnesium, MIPA, TIPA laureth sulfate, sodium myreth sulfate and sodium C._12-13 Pareth sulfate; (2) alkyl sulfates, e.g. sodium, ammonium and TEA lauryl sulfate.

Cationic surfactants to be used advantageously are alkylamines, alkylimidazoles, ethoxylated amines and quaternary surfactants and esterquats.

Quaternary surfactants contain at least one N atom that is covalently linked to 4 alkyl or aryl groups. Regardless of the pH value, this leads to a positive charge.

Alkyl betaine, alkyl amidopropyl betaine and alkyl amidopropyl hydroxysulfain are advantageous. The cationic surfactants used in accordance with the invention can furthermore preferably be selected from the group of the quaternary ammonium compounds, in particular benzyltrialkylammonium chlorides or bromides, such as, for example, benzyldimethylstearylammonium chloride, furthermore alkyltrialkylammonium salts, for example cetyltrimethylammonium chloride or bromide, alkyldimethylhydroxyethylbromidiumammonium chloride, or Alkylamidethyltrimethylammonium ether sulfates, alkylpyridinium salts, for example lauryl or cetylpyrimidinium chloride, imidazoline derivatives and compounds with a cationic character such as amine oxides, for example alkyldimethylamine oxides or alkylaminoethyldimethylamine oxides. Cetyltrimethylammonium salts are particularly advantageous.

Amphoteric surfactants to be used advantageously are (1) acyl- / dialkylethylenediamine, for example sodium acylamphoacetate, disodium acylamphodipropionate, disodium alkylamphodiacetate, sodium acylamphohydroxypropylsulfonate, disodium acylamphodiacetate and sodium acylamphopropionate; (2) N-alkylamino acids, e.g. aminopropylalkylglutamide, alkylaminopropionic acid, sodium alkylimidodipropionate and lauroamphocarboxyglycinate.

Nonionic surfactants to be used advantageously are (1) alcohols; (2) alkanolamides such as Cocamide MEA / DEA / MIPA; (3) amine oxides such as cocoamidopropylamine oxide; (4) esters formed by esterification of carboxylic acids with ethylene oxide, glycerin, sorbitan or other alcohols; (5) ethers, for example, ethoxylated / propoxylated alcohols, ethoxylated / propoxylated esters, ethoxylated / propoxylated glycerol esters, ethoxylated / propoxylated cholesterols, ethoxylated / propoxylated triglyceride esters, ethoxylated propoxylated lanolin, ethoxylated / propoxylated polysiloxanes, propoxylated POE ethers and alkyl laurylglyglycosyl glycylglycosides such as lauryl polyglycol glycosyl glycosides and cocoglycoside; (6) sucrose esters, ethers; (7) polyglycerol esters, diglycerol esters, monoglycerol esters; (8) methyl glucose esters, esters of hydroxy acids.

It is also advantageous to use a combination of anionic and / or amphoteric surfactants with one or more nonionic surfactants.

The surface-active substance can be present in the preparations according to the invention in a concentration between 1 and 95% by weight, based on the total weight of the preparations.

The lipid phase of the cosmetic or dermatological emulsions according to the invention can advantageously be selected from the following group of substances:<ul id="ul0003" list-style="dash"><li>Mineral oils, mineral waxes</li><li>Oils such as triglycerides of capric or caprylic acid, as well as natural oils such as castor oil;</li><li>Fats, waxes and other natural and synthetic fat bodies, preferably esters of fatty acids with alcohols with a low C number, for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids with a low C number or with fatty acids;</li><li>Alkyl benzoates;</li><li>Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.</li></ul>

The oil phase of the emulsions according to the present invention is advantageously selected from the group of the esters from saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched Alcohols with a chain length of 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon atoms. Such ester oils can then advantageously be selected from the group of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononylisononanoate, 2-ethylhexyl ethylate, 2-ethylhexyl ethylhexyl palate Octyldodecyl palmitate, oleyl oleate, olerlerucate, erucyl oleate, erucylerucate as well as synthetic, semi-synthetic and natural mixtures of such esters, for example jojoba oil.

Furthermore, the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and also the fatty acid triglycerides, especially the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12 - 18 carbon atoms. The fatty acid triglycerides can, for example, advantageously be selected from the group of synthetic, semisynthetic and natural oils, for example olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like.

Any mixtures of such oil and wax components can also be used advantageously for the purposes of the present invention. It may also be advantageous to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.

The oil phase is advantageously selected from the group consisting of 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate, C._12-15-Alkyl benzoate, caprylic-capric acid triglyceride, dicaprylyl ether.

Mixtures of C are particularly advantageous_12-15-Alkyl benzoate and 2-ethylhexyl isostearate, mixtures of C_12-15Alkyl benzoate and isotridecyl isononanoate and mixtures of C_12-15Alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.

Of the hydrocarbons, paraffin oil, squalane and squalene can be used advantageously for the purposes of the present invention.

Advantageously, the oil phase can also contain cyclic or linear silicone oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or the silicone oils. Such silicones or silicone oils can be present as monomers, which are generally characterized by structural elements, as follows:<chemistry id="chem0015" num="0015"><img file="EP1598421A2_D0015.tif" /></chemistry>

Linear silicones with a plurality of siloxy units which can advantageously be used according to the invention are generally characterized by structural elements as follows:<chemistry id="chem0016" num="0016"><img file="EP1598421A2_D0016.tif" /></chemistry> wherein the silicon atoms can be substituted with the same or different alkyl radicals and / or aryl radicals, which here are generalized by the radicals R₁ - R₄ (means that the number of different residues is not necessarily limited to up to 4). m can assume values ​​from 2 to 200,000.

Cyclic silicones to be used advantageously according to the invention are generally characterized by structural elements as follows<chemistry id="chem0017" num="0017"><img file="EP1598421A2_D0017.tif" /></chemistry> wherein the silicon atoms can be substituted with the same or different alkyl radicals and / or aryl radicals, which here are generalized by the radicals R₁ - R₄ (means that the number of different residues is not necessarily limited to up to 4). n can take values ​​from 3/2 to 20. Broken values ​​for n take into account that there may be odd numbers of siloxyl groups in the cycle.

Cyclomethicone (eg decamethylcyclopentasiloxane) is advantageously used as the silicone oil to be used according to the invention. However, other silicone oils can also be used advantageously for the purposes of the present invention, for example undecamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane), cetyldimethicone, behenoxydimethicone.

Mixtures of cyclomethicone and isotridecyl isononanoate and those of cyclomethicone and 2-ethylhexyl isostearate are also advantageous.

However, it is also advantageous to choose silicone oils of a similar constitution to the compounds described above, the organic side chains of which are derivatized, for example polyethoxylated and / or polypropoxylated. These include, for example, polysiloxane-polyalkyl-polyether copolymers such as the cetyl-dimethicone copolyol, the (cetyl-dimethicone copolyol (and) polyglyceryl-4-isostearate (and) hexyl laurate)

Mixtures of cyclomethicone and isotridecyl isononanoate, cyclomethicone and 2-ethylhexyl isostearate are also particularly advantageous.

The aqueous phase of the preparations according to the invention optionally advantageously contains alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether , Diethylenglykolmonomethyl- or -monoethylether and analogous products, furthermore low C-number alcohols, eg Ethanol, isopropanol, 1,2-propanediol, glycerin and in particular one or more thickeners, which one or more can advantageously be selected from the group consisting of silicon dioxide and aluminum silicates.

According to the invention, preparations present as emulsions particularly advantageously contain one or more hydrocolloids. These hydrocolloids can advantageously be selected from the group of the gums, polysaccharides, cellulose derivatives, layered silicates, polyacrylates and / or other polymers.

According to the invention, preparations present as hydrogels contain one or more hydrocolloids. These hydrocolloids can advantageously be selected from the aforementioned group.

Gums include plant or tree sap that harden in the air and

Forming resins or extracts from aquatic plants. Gum arabic, locust bean gum, tragacanth, karaya, guar gum, pectin, gellan gum, carrageenan, agar, algine, chondrus, xanthan gum can advantageously be selected from this group for the purposes of the present invention.

The use of derivatized gums such as hydroxypropyl guar (Jaguar® HP 8) is also advantageous.

The polysaccharides and derivatives include, for example, hyaluronic acid, chitin and chitosan, chondroitin sulfates, starch and starch derivatives.

The cellulose derivatives include, for example, methyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose.

Layered silicates include naturally occurring and synthetic clays such as montmorillonite, bentonite, hectorite, laponite, magnesium aluminum silicates such as Veegum®. These can be used as such or in a modified form, such as stearylalkonium hectorites.

Furthermore, silica gels can also advantageously be used.

The polyacrylates include, for example, Carbopol types from Goodrich (Carbopol 980, 981, 1382, 5984, 2984, EDT 2001 or Pemulen TR2).

The polymers include, for example, polyacrylamides (Seppigel 305), polyvinyl alcohols, PVP, PVP / VA copolymers, polyglycols.

According to a further preferred embodiment, the oligoribonucleotides used according to the invention are inserted into aqueous systems or surfactant preparations for cleaning the skin and hair.

Moisturizers are substances or mixtures of substances that give cosmetic or dermatological preparations the property that, after application or distribution on the skin surface, the release of moisture from the horny layer (also <u>t</u>rans-<u>e</u>pidermal <u>w</u>ater <u>l</u>oss (called TEWL)) and / or to positively influence the hydration of the horny layer. Advantageous moisturizers for the purposes of the present invention are, for example, glycerol, lactic acid, pyrrolidone carboxylic acid and urea. Furthermore, it is particularly advantageous to use polymeric moisturizers from the group of water-soluble and / or water-swellable and / or water-gelable polysaccharides. Particularly advantageous are, for example, hyaluronic acid and / or a fucose-rich polysaccharide, which is filed in the Chemical Abstracts under the registration number 178463-23-5 and z. B. is available under the name Fucogel □ 1000 from the company SOLABIA SA.

When used as a moisturizer, glycerin is preferably used in an amount of 0.05-30% by weight, particularly preferably 1-10%.

According to the invention, preparations present as emulsions contain one or more emulsifiers. These emulsifiers can advantageously be selected from the group of nonionic, anionic, cationic or amphoteric emulsifiers.

Among the nonionic emulsifiers are<ul id="ul0004" list-style="none" compact="compact"><li>a) Partial fatty acid esters and fatty acid esters of polyhydric alcohols and their ethoxylated derivatives (e.g. glyceryl monostearates, sorbitan stearates, glyceryl stearyl citrates, sucrose stearates)</li><li>b) ethoxylated fatty alcohols and fatty acids</li><li>c) ethoxylated fatty amines, fatty acid amides, fatty acid alkanolamides</li><li>d) alkylphenol polyglycol ether (e.g. Triton X)</li></ul>

Among the anionic emulsifiers are<ul id="ul0005" list-style="none" compact="compact"><li>a) soaps (e.g. sodium stearate)</li><li>b) fatty alcohol sulfates</li><li>c) mono-, di- and trialkylphosphonic acid esters and their ethoxylates</li></ul>

Among the cationic emulsifiers are<ul id="ul0006" list-style="none" compact="compact"><li>a) quaternary ammonium compounds with a long-chain aliphatic radical, for example distearyldimonium chloride</li></ul>

Among the amphoteric emulsifiers are<ul id="ul0007" list-style="none" compact="compact"><li>a) Alkylamininoalkane carboxylic acids</li><li>b) betaines, sulfobetaines</li><li>c) Imidazoline derivatives</li></ul>

There are also naturally occurring emulsifiers, which include beeswax, wool wax, lecithin and sterols.

O / W emulsifiers can, for example, advantageously be selected from the group of polyethoxylated or polypropoxylated or polyethoxylated and polypropoxylated products, for example:<ul id="ul0008" list-style="dash"><li>the fatty alcohol ethoxylates</li><li>the ethoxylated wool wax alcohols,</li><li>the polyethylene glycol ether of the general formula RO - (- CH₂-CH₂-O-)_n-R ',</li><li>the fatty acid ethoxylates of the general formula         R-COO - (- CH₂-CH₂-O-)_n -H,</li><li>the etherified fatty acid ethoxylates of the general formula         R-COO - (- CH₂-CH₂-O-)_n-R ',</li><li>the esterified fatty acid ethoxylates of the general formula         R-COO - (- CH₂-CH₂-O-)_n-C (O) -R ',</li><li>the polyethylene glycol glycerol fatty acid ester</li><li>the ethoxylated sorbitan esters</li><li>the cholesterol ethoxylates</li><li>the ethoxylated triglycerides</li><li>the alkyl ether carboxylic acids of the general formula         RO - (- CH₂-CH₂-O-)_n-CH₂-COOH and n represent a number from 5 to 30,</li><li>the polyoxyethylene sorbitol fatty acid ester,</li><li>the alkyl ether sulfates of the general formula RO - (- CH₂-CH₂-O-)_n-SO₃-H</li><li>the fatty alcohol propoxylates of the general formula         RO - (- CH₂-CH (CH₃)-O-)_n-H,</li><li>the polypropylene glycol ether of the general formula         RO - (- CH₂-CH (CH₃)-O-)_nR ',</li><li>the propoxylated wool wax alcohols,</li><li>the etherified fatty acid propoxylates         R-COO - (- CH₂-CH (CH₃)-O-)_n-R ',</li><li>the esterified fatty acid propoxylates of the general formula         R-COO - (- CH₂-CH (CH₃)-O-)_n-C (O) -R ',</li><li>the fatty acid propoxylates of the general formula         R-COO - (- CH₂-CH (CH₃)-O-)_n-H,</li><li>the polypropylene glycol glycerol fatty acid ester</li><li>the propoxylated sorbitan esters</li><li>the cholesterol propoxylates</li><li>of the propoxylated triglycerides</li><li>the alkyl ether carboxylic acids of the general formula         RO - (- CH₂-CH (CH₃)O-)_nCH₂-COOH</li><li>the alkyl ether sulfates or the acids of the general formula RO - (- CH₂-CH (CH₃)-O-)_n-SO₃-H</li><li>the fatty alcohol ethoxylates / propoxylates of the general formula         ROX_n-Y_m-H,</li><li>the polypropylene glycol ether of the general formula         ROX_n-Y_m-R ',</li><li>the etherified fatty acid propoxylates of the general formula         R-COO-X_n-Y_m-R ',</li><li>the fatty acid ethoxylates / propoxylates of the general formula         R-COO-X_n-Y_m-H,.</li></ul>

According to the invention, the polyethoxylated or polypropoxylated or polyethoxylated and polypropoxylated O / W emulsifiers selected are particularly advantageously selected from the group of substances with HLB values ​​of 11-18, very particularly advantageously with HLB values ​​of 14.5-15. 5, provided the O / W emulsifiers have saturated radicals R and R '. If the O / W emulsifiers have unsaturated radicals R and / or R ', or if isoalkyl derivatives are present, the preferred HLB value of such emulsifiers can also be lower or higher.

It is advantageous to choose the fatty alcohol ethoxylates from the group of the ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). The following are particularly preferred:

Polyethylene glycol (13) stearyl ether (steareth-13), polyethylene glycol (14) stearyl ether (steareth-14), polyethylene glycol (15) stearyl ether (steareth-15), polyethylene glycol (16) stearyl ether (steareth-16), polyethylene glycol (17) stearyl ether (Steareth-17), polyethylene glycol (18) stearyl ether (Steareth-18), polyethylene glycol (19) stearyl ether (Steareth-19), polyethylene glycol (20) stearyl ether (Steareth-20),

Polyethylene glycol (12) isostearyl ether (isosteareth-12), polyethylene glycol (13) isostearyl ether (isosteareth-13), polyethylene glycol (14) isostearyl ether (isosteareth-14), polyethylene glycol (15) isostearyl ether (isosteareth-15), polyethylene glycol (16) isostearyl ether ( Isosteareth-16), polyethylene glycol (17) isostearyl ether (isosteareth-17), polyethylene glycol (18) isostearyl ether (isosteareth-18), polyethylene glycol (19) isostearyl ether (isosteareth-19), polyethylene glycol (20) isostearyl ether (isosteareth-20),

Polyethylene glycol (13) cetyl ether (ceteth-13), polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol (15) cetyl ether (ceteth-15), polyethylene glycol (16) cetyl ether (ceteth-16), polyethylene glycol (17) cetyl ether ( Ceteth-17), polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol (19) cetyl ether (ceteth-19), polyethylene glycol (20) cetyl ether (ceteth-20),

Polyethylene glycol (13) isocetyl ether (isoceteth-13), polyethylene glycol (14) isocetyl ether (isoceteth-14), polyethylene glycol (15) isocetyl ether (isoceteth-15), polyethylene glycol (16) isocetyl ether (isoceteth-16), polyethylene glycol (17) isocetyl ether (Isoceteth-17), polyethylene glycol (18) isocetyl ether (isoceteth-18), polyethylene glycol (19) isocetyl ether (isoceteth-19), polyethylene glycol (20) isocetyl ether (isoceteth-20),

Polyethylene glycol (12) oleyl ether (Oteth-12), polyethylene glycol (13) oleyl ether (Oleth-13), polyethylene glycol (14) oleyl ether (Oleth-14), polyethylene glycol (15) oleyl ether (Oleth-15),

Polyethylene glycol (12) lauryl ether (Laureth-12), polyethylene glycol (12) isolauryl ether (Isolaureth-12).

Polyethylene glycol (13) cetyl stearyl ether (ceteareth-13), polyethylene glycol (14) cetyl stearyl ether (ceteareth-14), polyethylene glycol (15) cetyl stearyl ether (ceteareth-15), polyethylene glycol (16) cetyl stearyl ether (ceteareth-16), polyethylene glycol (17) Ceteareth-17), polyethylene glycol (18) cetylstearyl ether (ceteareth-18), polyethylene glycol (19) cetylstearyl ether (ceteareth-19), polyethylene glycol (20) cetylstearyl ether (ceteareth-20),

It is also advantageous to choose the fatty acid ethoxylates from the following group:

Polyethylene glycol (20) stearate, polyethylene glycol (21) stearate, polyethylene glycol (22) stearate, polyethylene glycol (23) stearate, polyethylene glycol (24) stearate, polyethylene glycol (25) stearate,

Polyethylene glycol (12) isostearate, polyethylene glycol (13) isostearate, polyethylene glycol (14) isostearate, polyethylene glycol (15) isostearate, polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate, polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate (20) isostearate, polyethylene glycol (21) isostearate, polyethylene glycol (22) isostearate, polyethylene glycol (23) isostearate, polyethylene glycol (24) isostearate, polyethylene glycol (25) isostearate,

Polyethylene glycol (12) oleate, Polyethylene glycol (13) oleate, Polyethylene glycol (14) oleate, Polyethylene glycol (15) oleate, Polyethylene glycol (16) oleate, Polyethylene glycol (17) oleate, Polyethylene glycol (18) oleate, Polyethylene glycol (19) oleate, Polyethylene glycol ( 20) oleate

Sodium laureth-11 carboxylate can advantageously be used as the ethoxylated alkyl ether carboxylic acid or its salt.

Sodium laureth 1-4 sulfate can advantageously be used as alkyl ether sulfate.

Polyethylene glycol (30) cholesteryl ether can advantageously be used as the ethoxylated cholesterol derivative. Polyethylene glycol (25) soyasterol has also proven itself.

Polyethylene glycol (60) evening primrose glycerides can advantageously be used as ethoxylated triglycerides (evening primrose = evening primrose)

Another advantage is the polyethylene glycol glycerol fatty acid esters from the group polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate / caprinate 20, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate / cocoat to choose.

It is also favorable to choose the sorbitan esters from the group consisting of polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan monoisostearate, polyethylene glycol (20) sorbitan monopalmitate, polyethylene glycol (20) sorbitan monooleate.

The following can be used as advantageous W / O emulsifiers: Fatty alcohols with 8 to 30 carbon atoms, monoglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12-18 C atoms, diglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length from 8 to 24, in particular 12 - 18 carbon atoms, monoglycerol ethers of saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 8 to 24, in particular 12 - 18 C-atoms, diglycerol ethers of saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 8 to 24, in particular 12 - 18 C-atoms, propylene glycol ester saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12 - 18 carbon atoms and sorbitan esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12 - 18 carbon atoms.

Particularly advantageous W / O emulsifiers are glyceryl monostearate, glyceryl, glyceryl monomyristate, glyceryl, diglyceryl monostearate, Diglycerylmonoisostearat, propylene glycol, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol, sorbitan, sorbitan, sorbitan, Sorbitanmonoisooleat, sucrose, cetyl alcohol, stearyl, arachidyl, behenyl, Isobehenylalkohol, Selachyl alcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether (steareth-2), glyceryl monolaurate, glyceryl monocaprinate, glyceryl monocaprylate.

Fabric list deodorant / AT

In addition to water, ethanol and isopropanol, glycerol and propylene glycol, skin-caring fat or fat-like substances, such as oleic acid decyl ester, cetyl alcohol, cetylstearyl alcohol and 2-octyldodecanol, can be used as customary cosmetic carriers for the preparation of the deodorant preparations according to the use according to the invention in the quantitative ratios customary for such preparations, in addition to water as well as slime-forming substances and thickeners, e.g. Hydroxyethyl or hydroxypropyl cellulose, polyacrylic acid, polyvinylpyrrolidone, but also in small quantities cyclic silicone oils (polydimethylsiloxanes) and liquid polymethylphenylsiloxanes with low viscosity.

It is advantageous if the preparations according to the invention contain, in addition to the combination of active ingredients, astringents or antiperspirants, silicone oils and / or powder substances.

Antiperspirants come e.g. B. Aluminum chlorohydates in question. These are colorless, hygroscopic crystals that easily dissolve in the air and arise when aqueous aluminum chloride solutions are evaporated. Aluminum chlorohydrate is used in the manufacture of antiperspirant and deodorant preparations and is likely to act by partially occluding the sweat glands through protein and / or polysaccharide precipitation. In addition to the chlorohydrates, aluminum hydroxyl octates and acidic aluminum / zirconium salts can also be used.<ul id="ul0009" list-style="bullet" compact="compact"><li>Aluminum salts (the empirical empirical formula [Al₂(OH)_mCl_n], where m + n = 6):</li></ul><ul id="ul0010" list-style="bullet"><li>Aluminum salts such as aluminum chloride AlCl₃, Aluminum sulfate Al₂(SO₄)₃</li><li>Aluminum chlorohydrate [Al₂(OH)₅Cl] x H₂O</li><li>Standard Al complexes: Locron L (Clariant), chlorohydrol (Reheis), ACH-303 (Summit), Aloxicoll L (Giulini).</li><li>Activated Al complexes: Reach 501 (Reheis), AACH-324 (Summit)</li><li>Aluminum sesquichlorohydrate [Al₂(OH)_4,5Cl_1,5] x H₂O</li><li>Standard Al complexes: Aluminum Sesquichlorohydrate (Reheis), ACH-308 (Summit), Aloxicoll 31 L (Giulini)</li><li>Activated Al complexes: Reach 301 (Reheis)</li><li>Aluminum dichlorohydrate [Al₂(OH)₄Cl₂] x H₂O</li><li>Aluminum-zirconium salts:</li></ul><ul id="ul0011" list-style="bullet"><li>Aluminum / zirconium trichlorohydrex glycine [Al₄Zr (OH)₁₃Cl₃] x H₂O x Gly</li><li>Standard Al / Zr complexes: Rezal 33GP (Reheis), AZG-7164 (Summit), Zirkonal P3G (Giulini)</li><li>Activated Al / Zr complexes: Reach AZZ 902 (Reheis), AAZG-7160 (Summit), Zirkonal AP3G (Giulini)</li><li>Aluminum / zirconium tetrachlorohydrex glycine [Al₄Zr (OH)₁₂Cl₄] x H₂O x Gly</li><li>Standard Al / Zr complexes: Rezal 36G (Reheis), AZG-368 (Summit), Zirkonal L435G (Giulini)</li><li>Activated Al / Zr complexes: Reach AZP 855 (Reheis), AAZG-6313-15 (Summit), Zirkonal AP4G (Giulini)</li><li>Aluminum / zirconium pentachlorohydrex glycine [Al₈Zr (OH)₂₃Cl₅] x H₂O x Gly</li><li>Standard Al / Zr complexes: Rezal 67 (Reheis), Zirkonal L540 (Giulini)</li><li>Activated Al / Zr complexes: Reach AZN 885 (Reheis)</li><li>Aluminum / zirconium octachlorohydrex glycine [Al₈Zr (OH)₂₀Cl₈] x H₂O x Gly</li></ul>

Glycine-free aluminum / zirconium salts can also be advantageous.

The use of antiperspirants from the raw material classes aluminum and aluminum / zirconium salts should not be limited to the commercially available, mostly aqueous solutions, such as Locron L (Clariant), but it can also be advantageous to use the commercially available anhydrous solutions Powder of the same raw materials can be used by incorporating them into the claimed formulations, such as Locron P (Clariant).

The use of so-called AT salt suspensions could also be advantageous, in which aluminum and aluminum / zirconium salts in powder form are offered in dispersed form in various oils.

Furthermore, it can also be advantageous to use special aluminum and aluminum / zirconium salts, which are offered as glycol complexes to improve solubility.

Other advantageous antiperspirants are based on other metals, such as beryllium, titanium, hafnium, instead of aluminum or zirconium.

However, the list of antiperspirant active ingredients which can be used is not limited to metal-containing raw materials, but also compounds which contain non-metals such as boron and those which are classified in the field of organic chemistry, such as anticholinergics, are advantageous.

In this sense, polymers which can be both metal-containing and metal-free are also advantageous.

Suitable propellants for dermatological preparations according to the invention which can be sprayed from aerosol containers are the customary known volatile, liquefied propellants, for example hydrocarbons (propane, butane, isobutane), which can be used alone or in a mixture with one another. Compressed air can also be used advantageously.

Of course, the person skilled in the art knows that there are non-toxic propellant gases per se which would in principle be suitable for the present invention, but which should nevertheless be dispensed with, in particular fluorochlorohydrocarbons (CFCs), because of their harmful effects on the environment or other associated circumstances.

In addition, sprayable preparations contain certain oil components and alcohols ethanol and isopropanol, glycerol and propylene glycol, skin-care fat or fat-like substances, such as oleic acid decyl ester, cetyl alcohol, cetylstearyl alcohol and 2-octyldodecanol, in the proportions customary for such preparations , and slime-forming substances and thickeners, for example Hydroxyethyl or hydroxypropyl cellulose, polyacrylic acid, polyvinylpyrrolidone, but also in small quantities cyclic silicone oils (polydimethylsiloxanes) and liquid polymethylphenylsiloxanes with low viscosity.

In all of these it is possible in individual cases that the above-mentioned concentration values ​​are slightly exceeded or fallen short of and that preparations according to the invention are nevertheless obtained. In view of the wide-ranging diversity of suitable components of such preparations, this is not unexpected for the person skilled in the art, so that he knows that in the event of such overshoots or undershoots, the scope of the present invention is not left.

The following examples are intended to illustrate the present invention without restricting it. The numerical values ​​in the examples mean percentages by weight, based on the total weight of the respective preparations.

Examples

Example 1: Measurement of the inhibition of TGFbeta-1 expression in human dermal fibroblasts by dsRNA

Human dermal fibroblasts (HDF cells) were used to determine the effectiveness of oligoribonucleotides according to the invention. The TGFbeta-1 growth factor is expressed endogenously by the cells.

For this purpose, the cells (in DMEM with 10% fetal calf serum) were sown on the day before induction at a density of 7x105 cells per 10 cm dish and for 24 hours in the full medium (DMEM + 10% FCS + 1% Glutamax + 1% Pen / Strep) cultivated. The transfection was carried out using a mixture of cationic lipids (oligofectamine reagent, Invitrogen). For the transfection batch, 90 μl of the various anti-TGFbeta-1 dsRNAs (dsRNAs, which were obtained by hybridizing the sequences SEQ ID NOs 15 and 16, SEQ ID NOs 18 and 19 and SEQ ID NOs 6 and 7, respectively) were the dsRNAs have 3 'in each case two protruding dT residues, see Figure 2) dissolved in 1.5 ml of medium. In a second approach, 36 ul oligofectamine was dissolved in 240 ul medium and incubated for 5-10 min. After this incubation period, the two batches were combined and incubated for a further 15-20 minutes. In the meantime, the complete medium was removed from the cells and replaced by 7 ml of medium without the addition of antibiotics or serum. The transfection batch was now applied to the cells. This transfection batch was then left on the primary fibroblasts for 24 hours. Samples which were not transfected with dsRNA or those which were not transfected with a dsRNA which did not bind the TGFbeta-1 (anti-LaminA / C control oligoribonucleotides from MWG) served as comparison.

After microscopic examination of the cells, the total RNA was isolated. The medium supernatant was removed and the cells were rinsed once with PBS. The cells were covered with 200µm PBS and 400µl lysis buffer, scraped off and transferred to Eppendorf tubes. The RNA isolation was carried out using the High Pure RNA Isolation Kit (Roche Diagnostics Corp.) according to the manufacturer's instructions. The isolated RNA bound to a column was eluted with 50-100 µl water.

The content of TGFbeta-1 mRNA was determined from the isolated RNA using the quantitative TaqMan analysis (TaqMan Assays-on-Demand ™, Applied Biosystems).

For this purpose, the total RNA was first rewritten into cDNA in a 2-step process. Reverse transcription was carried out using the<i>High Capacity cDNA Archives</i> Kits (Applied Biosystems) carried out according to the manufacturer's instructions.

In the quantitative PCR, 1 µl of the cDNA reaction (corresponds to 10 ng total RNA) with 10.25 µl water, 12.5 µl TaqMan Universal Master Mix (with AmpliTaq gold polymerase) and 1.25 µl target mix ( specific primer and fluorescence-labeled sample) for 18S-RNA as a control or TGF-β1. In the ABI PRISM 7700, the samples were first incubated at 50 ° C for 2 min to activate uracil-N-glycolase, followed by a 10-minute inactivation at 95 ° C. The PCR was carried out over 40 cycles at 95 ° C (15 s) (denaturation) and 60 ° C (1 min) (annealing). The change in fluorescence is detected by the ABI PRISM 7700 during the PCR.

Gene expression was quantified via the C_TValue (threshold cycle). The relativization took place via the endogenous control of the 18s RNA.

The mean values ​​were formed from the triple determinations of target gene (TGFbeta-1) and endogenous control (18sRNA) per sample and these were then divided (ng sample / ng control). In this way, normalized, unitless values ​​of the relative quantitative expression of the target gene were obtained.

The results are shown graphically in FIG. 6. The relative mRNA concentration of the growth factor TGFbeta-1, normalized via the 18S rRNA content, can be seen here in a percentage relationship to the control. Transfection of the cells with the transfection reagent alone ("without siRNA") and with the oligoribonucleotides against Lamin A / C ("control") does not change the TGFbeta-1 mRNA content. The transfection with the three different oligoribonucleotide pairs against TGFbeta-1, however, leads to a decrease in the TGFbeta-1 concentration ("SEQ ID NOs" 15 + 16 "," 18 + 19 "and" 6 + 7 "). The inhibition is approximately 80-90% compared to the control and the cells not transfected with siRNA.

In Figure 1, the coding sequence of TGFbeta-1 is shown (SEO ID NO 1). The oligoribonucleotides used are highlighted, which are characterized in that they are homologous to such a section of the target gene and in particular to the corresponding double-stranded cDNA, the sense strand of which is 5'-sided by two adenosine residues (<b>AA</b>) and at a distance of 19 bases on the 3 'side through two thymidine residues (<u><b>tt</b></u>), a guanosine and a cytosine residue (<u><b>gc</b></u>) or a thymidine and a cytidine residue (<u><b>tc</b></u>) is limited.

Example 2: Oligoribonucleotides to Inhibit Sonic Hedgehog Expression

The coding DNA sequence (SEQ ID NO 20) of the Sonic Hedgehog is shown in FIG. 3. The oligoribonucleotides used are highlighted, which are characterized in that they are homologous to such a section of the target gene and in particular to the corresponding double-stranded cDNA, the sense strand of which is 5'-sided by two adenosine residues (<b>AA</b>) and at a distance of 19 bases on 3 'side by a guanosine (<u><b>G</b></u>) and a cytosine residue (<u><b>c</b></u>) or a thymidine (<u><b>t</b></u>) and a cytidine residue (<u><b>c</b></u>) is limited.

Example 3: Oligoribonucleotides for Inhibiting Androgen Receptor Expression

The coding DNA sequence (SEQ ID NO 21) of the androgen receptor is shown in FIG. 4. The oligoribonucleotides used are highlighted, which are characterized in that they are homologous to such a section of the target gene and in particular to the corresponding double-stranded cDNA, the sense strand of which is 5'-sided by two adenosine residues (<b>AA</b>) and at a distance of 19 bases on the 3 'side through two thymidine residues (<u><b>t</b></u>), a guanosine (<u><b>G</b></u>) and a cytosine residue (<u><b>c</b></u>) or a thymidine (<u><b>t</b></u>) and a cytidine residue (<u><b>c</b></u>) is limited.

Example 4: Oligoribonucleotides for Inhibiting the Expression of Insulin-Like Growth Factor 1

The coding DNA sequence (SEQ ID NO 22) of the insulin-like growth factor 1 is shown in FIG. 5. The oligoribonucleotides used are highlighted, which are characterized in that they are homologous to such a section of the target gene and in particular to the corresponding double-stranded cDNA, the sense strand of which is 5'-sided by two adenosine residues (<b>AA</b>) and at a distance of 19 bases on the 3 'side through two thymidine residues (<u><b>t</b></u>), a guanosine (<u><b>G</b></u>) and a cytosine residue (<u><b>c</b></u>) or a thymidine (<u><b>t</b></u>) and a cytidine residue (<u><b>c</b></u>) is limited.

Example 5: Preparation of PIT Emulsions

Phase inversion temperature emulsions (PIT emulsions) of the composition likewise given were prepared by mixing the components indicated in the table. The oligoribonucleotide used was dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 22. SEQ ID NO 22 is a section of the cDNA of insulin-like growth factor 1 (see FIG. 5). The two strands of the dsRNA each had two 2'-deoxythymidine residues at the 3 'position. The dsRNA is specific for the cDNA of the IGF-1 and inhibits the expression of the gene of this enzyme by RNA interference. It is therefore called anti-IGF-1 dsRNA. The other abbreviations used in the examples are to be understood accordingly.<tables id="tabl0001" num="0001"><table frame="all"><title>Table 1:</title><tgroup cols="6" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="26.25mm" /><colspec colnum="2" colname="col2" colwidth="26.25mm" /><colspec colnum="3" colname="col3" colwidth="26.25mm" /><colspec colnum="4" colname="col4" colwidth="26.25mm" /><colspec colnum="5" colname="col5" colwidth="26.25mm" /><colspec colnum="6" colname="col6" colwidth="26.25mm" /><thead valign="top"><row><entry namest="col1" nameend="col6" align="left"><b>PIT emulsions</b></entry></row><row><entry namest="col1" nameend="col1" align="left"><b>Emulsion No.</b></entry><entry namest="col2" nameend="col2" align="left"><b>1</b></entry><entry namest="col3" nameend="col3" align="left"><b>2</b></entry><entry namest="col4" nameend="col4" align="left"><b>3</b></entry><entry namest="col5" nameend="col5" align="left"><b>4</b></entry><entry namest="col6" nameend="col6" align="left"><b>5</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Self-emulsifying glycerol monostearate</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">3,00</entry><entry namest="col5" nameend="col5" align="left">2,00</entry><entry namest="col6" nameend="col6" align="left">4,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyoxyethylene (12) cetyl stearyl ether</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">5,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">1,00</entry><entry namest="col6" nameend="col6" align="left">1,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyoxyethylene (20) cetyl stearyl ether</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">2,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Polyoxyethylene (30) cetyl stearyl ether</entry><entry namest="col2" nameend="col2" align="left">5,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">1,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Stearyl alcohol</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">3,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetyl alcohol</entry><entry namest="col2" nameend="col2" align="left">2,50</entry><entry namest="col3" nameend="col3" align="left">1,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">1,50</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">2-ethylhexyl methoxy tin amate</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">5,00</entry><entry namest="col6" nameend="col6" align="left">8,00</entry></row><row><entry namest="col1" nameend="col1" align="left">2,4-bis (4- (2-ethylhexyloxy) 2-hydroxyl) phenyl) -6- (4-methoxyphenyl) - (1,3,5) triazine</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">1,50</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">2,00</entry><entry namest="col6" nameend="col6" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">1- (4-tert-Butylphenyl) -3- (4-methoxyphenyl) -1,3-propanedione</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">2,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Diethylhexyl butamidotriazon</entry><entry namest="col2" nameend="col2" align="left">1,00</entry><entry namest="col3" nameend="col3" align="left">2,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">2,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Ethylhexyl triazon</entry><entry namest="col2" nameend="col2" align="left">4,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">3,00</entry><entry namest="col5" nameend="col5" align="left">4,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">4-methylbenzylidene camphor</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">4,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Octocrylene</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">4,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Phenylene-1,4-bis (monosodium, 2-benzimidazyl-5,7-disulfonic acid</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">0,50</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">1,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Phenylbenzimidazole sulfonic acid</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">3,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">C12-15 alkyl benzoate</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">2,50</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">5,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Titanium dioxide</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" align="left">1,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">3,00</entry><entry namest="col6" nameend="col6" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">zinc oxide</entry><entry namest="col2" nameend="col2" align="left">2,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">3,00</entry><entry namest="col5" nameend="col5" align="left">0,50</entry><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Dicaprylyl ether</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">3,50</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Butylene glycol dicaprylate / dicaprate</entry><entry namest="col2" nameend="col2" align="left">5,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">6,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Dicaprylyl carbonate</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">6,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Dimethicone polydimethylsiloxane</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">0,50</entry><entry namest="col4" nameend="col4" align="left">1,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Phenylmethylpolysiloxane</entry><entry namest="col2" nameend="col2" align="left">2,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">0,50</entry><entry namest="col6" nameend="col6" align="left">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Shea butter</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">2,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">PVP hexadecene copolymer</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">0,50</entry><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="left">3,00</entry><entry namest="col3" nameend="col3" align="left">7,50</entry><entry namest="col4" nameend="col4" align="left">5,00</entry><entry namest="col5" nameend="col5" align="left">7,50</entry><entry namest="col6" nameend="col6" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Tocopherol acetate</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">0,25</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-IGF-1 dsRNA (consisting of the sequence with No. 44 and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="left">0,10</entry><entry namest="col3" nameend="col3" align="left">0,10</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">0,10</entry><entry namest="col6" nameend="col6" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry><entry namest="col5" nameend="col5" align="left">qs</entry><entry namest="col6" nameend="col6" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">Ethanol</entry><entry namest="col2" nameend="col2" align="left">3,00</entry><entry namest="col3" nameend="col3" align="left">2,00</entry><entry namest="col4" nameend="col4" align="left">1,50</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry><entry namest="col5" nameend="col5" align="left">qs</entry><entry namest="col6" nameend="col6" align="left">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad.100</entry><entry namest="col3" nameend="col3" align="left">ad.100</entry><entry namest="col4" nameend="col4" align="left">ad. 100</entry><entry namest="col5" nameend="col5" align="left">ad.100</entry><entry namest="col6" nameend="col6" align="left">ad.100</entry></row></tbody></tgroup></table></tables>

In an analogous manner, a PIT emulsion was produced using dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 20.

Example 6: Preparation of creams based on oil-in-water emulsions

By mixing the components specified in the table, creams of the composition likewise specified were prepared.<tables id="tabl0002" num="0002"><img file="EP1598421A2_D0018.tif" /></tables><tables id="tabl0003" num="0003"><img file="EP1598421A2_D0019.tif" /></tables><tables id="tabl0004" num="0004"><img file="EP1598421A2_D0020.tif" /></tables><tables id="tabl0005" num="0005"><img file="EP1598421A2_D0021.tif" /></tables>

In an analogous manner, a PIT emulsion was produced using dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 20.

Example 7: Preparation of water-in-oil emulsions

Water-in-oil emulsions of the composition likewise given were prepared by mixing the components given in the table. The oligoribonucleotide used was dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 22. SEQ ID NO 22 is a section of the cDNA of insulin-like growth factor 1 (see FIG. 5). The two strands of the dsRNA each had two 2'-deoxythymidine residues at the 3 'position.<tables id="tabl0006" num="0006"><img file="EP1598421A2_D0022.tif" /></tables><tables id="tabl0007" num="0007"><img file="EP1598421A2_D0023.tif" /></tables><tables id="tabl0008" num="0008"><img file="EP1598421A2_D0024.tif" /></tables><tables id="tabl0009" num="0009"><img file="EP1598421A2_D0025.tif" /></tables>

Example 8: Preparation of hydrodispersions

By mixing the components given in the table, hydrodispersions of the composition also given were prepared. The oligoribonucleotide used was dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 20. SEQ ID NO 20 is a section of the Sonic Hedgehog cDNA (see Figure 3). The two strands of the dsRNA each had two 2'-deoxythymidine residues at the 3 'position.<tables id="tabl0010" num="0010"><table frame="all"><title>Table 4:</title><tgroup cols="6" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="26.25mm" /><colspec colnum="2" colname="col2" colwidth="26.25mm" /><colspec colnum="3" colname="col3" colwidth="26.25mm" /><colspec colnum="4" colname="col4" colwidth="26.25mm" /><colspec colnum="5" colname="col5" colwidth="26.25mm" /><colspec colnum="6" colname="col6" colwidth="26.25mm" /><thead valign="top"><row><entry namest="col1" nameend="col6" align="left"><b>Hydrodispersions</b></entry></row><row><entry namest="col1" nameend="col1" align="left"><b>Dispersion No.</b></entry><entry namest="col2" nameend="col2" align="left"><b>1</b></entry><entry namest="col3" nameend="col3" align="left"><b>2</b></entry><entry namest="col4" nameend="col4" align="left"><b>3</b></entry><entry namest="col5" nameend="col5" align="left"><b>4</b></entry><entry namest="col6" nameend="col6" align="left"><b>5</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Polyoxyethylene (20) cetyl stearyl ether</entry><entry namest="col2" nameend="col2" align="left">1,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">0,5</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Cetyl alcohol</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">1,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Sodium polyacrylate</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">0,20</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">0,30</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Acrylate / C10-30 alkyl acrylate cross polymer</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">0,40</entry><entry namest="col5" nameend="col5" align="left">0,10</entry><entry namest="col6" nameend="col6" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Xanthan gum</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">0,30</entry><entry namest="col4" nameend="col4" align="left">0,15</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">2-ethylhexyl methoxy tin amate</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">5,00</entry><entry namest="col6" nameend="col6" align="left">8,00</entry></row><row><entry namest="col1" nameend="col1" align="left">2,4-bis (4- (2-ethylhexyloxy) 2-hydroxyl) phenyl) -6- (4-methoxyphenyl) - (1,3,5) triazine</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">1,50</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">2,00</entry><entry namest="col6" nameend="col6" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">1- (4-tert-Butylphenyl) -3- (4-methoxyphenyl) -1,3-propanedione</entry><entry namest="col2" nameend="col2" align="left">1,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">2,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Diethylhexyl butamidotriazon</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">2,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">2,00</entry><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Ethylhexyl triazon</entry><entry namest="col2" nameend="col2" align="left">4,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">3,00</entry><entry namest="col5" nameend="col5" align="left">4,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">4-methylbenzylidene camphor</entry><entry namest="col2" nameend="col2" align="left">4,00</entry><entry namest="col3" nameend="col3" align="left">4,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Octocrylene</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">4,00</entry><entry namest="col4" nameend="col4" align="left">4,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Phenylene-1,4-bis (monosodium, 2-bsnzimidazyl-5,7-disulfonic acid</entry><entry namest="col2" nameend="col2" align="left">1,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">0,50</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Phenylbenzimidazole sulfonic acid</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">3,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Titanium dioxide</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">2,00</entry><entry namest="col5" nameend="col5" align="left">3,00</entry><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">zinc oxide</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" align="left">1,00</entry><entry namest="col4" nameend="col4" align="left">3,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">C12-15 alkyl benzoate</entry><entry namest="col2" nameend="col2" align="left">2,00</entry><entry namest="col3" nameend="col3" align="left">2,50</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Dicaprylyl ether</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">4,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Butylene glycol dicaprylate / dicaprate</entry><entry namest="col2" nameend="col2" align="left">4,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">2,00</entry><entry namest="col5" nameend="col5" align="left">6,00</entry><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Dicaprylyl carbonate</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">2,00</entry><entry namest="col4" nameend="col4" align="left">6,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Dimethicone polydimethylsiloxane</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">0,50</entry><entry namest="col4" nameend="col4" align="left">1,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Phenylmethylpolysiloxane</entry><entry namest="col2" nameend="col2" align="left">2,00</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">0,50</entry><entry namest="col6" nameend="col6" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Shea butter</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" align="left">2,00</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">PVP hexadecene copolymer</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">0,50</entry><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Octoxyglycerin</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">1,00</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="left">3,00</entry><entry namest="col3" nameend="col3" align="left">7,50</entry><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" align="left">7,50</entry><entry namest="col6" nameend="col6" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycine soy</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">1,50</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" /></row><row><entry namest="col1" nameend="col1" align="left">Tocopherol acetate</entry><entry namest="col2" nameend="col2" align="left">0,50</entry><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" align="left">0,25</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-sonic hedgehog dsRNA (consisting of the sequence with the number 17 and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="left">0,10</entry><entry namest="col3" nameend="col3" align="left">0,10</entry><entry namest="col4" nameend="col4" align="left">0,10</entry><entry namest="col5" nameend="col5" align="left">0,10</entry><entry namest="col6" nameend="col6" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry><entry namest="col5" nameend="col5" align="left">qs</entry><entry namest="col6" nameend="col6" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">Ethanol</entry><entry namest="col2" nameend="col2" align="left">3,00</entry><entry namest="col3" nameend="col3" align="left">2,00</entry><entry namest="col4" nameend="col4" align="left">1,50</entry><entry namest="col5" nameend="col5" /><entry namest="col6" nameend="col6" align="left">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry><entry namest="col5" nameend="col5" align="left">qs</entry><entry namest="col6" nameend="col6" align="left">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad.100</entry><entry namest="col3" nameend="col3" align="left">ad.100</entry><entry namest="col4" nameend="col4" align="left">ad. 100</entry><entry namest="col5" nameend="col5" align="left">ad.100</entry><entry namest="col6" nameend="col6" align="left">ad.100</entry></row></tbody></tgroup></table></tables>

Example 9: Preparation of a gel cream

A gel cream of the composition likewise given was prepared by mixing the components indicated in the table. The pH of the gel cream was then adjusted to 6.0.<tables id="tabl0011" num="0011"><table frame="all"><title>Table 5:</title><tgroup cols="2" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="left"><b>Gel cream</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Acrylate / C10-30 alkyl acrylate crosspolymer</entry><entry namest="col2" nameend="col2" align="char" char=",">0,40</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyacrylic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">0,20</entry></row><row><entry namest="col1" nameend="col1" align="left">Xanthan gum</entry><entry namest="col2" nameend="col2" align="char" char=",">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetearyl alcohol</entry><entry namest="col2" nameend="col2" align="char" char=",">3,00</entry></row><row><entry namest="col1" nameend="col1" align="left">C12-15 alkyl benzoate</entry><entry namest="col2" nameend="col2" align="char" char=",">4,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Caprylic / Capric triglyceride</entry><entry namest="col2" nameend="col2" align="char" char=",">3,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Cyclic dimethylpolysiloxane</entry><entry namest="col2" nameend="col2" align="char" char=",">5,00</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-IGF-1 dsRNA (consisting of the sequence with No. 44 and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="char" char=",">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="char" char=",">3,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Sodium hydroxide</entry><entry namest="col2" nameend="col2" align="char" char=",">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative</entry><entry namest="col2" nameend="col2" align="char" char=",">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="char" char=",">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="char" char=",">ad 100.0</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">pH adjusted to 6.0</entry><entry namest="col2" nameend="col2" /></row></tbody></tgroup></table></tables>

In an analogous manner, a gel cream was produced using dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 20.

Example 10: Preparation of a cream based on a water-in-oil emulsion

By mixing the components specified in the table, a cream of the composition likewise specified was prepared on the basis of a water-in-oil dispersion. <tables id="tabl0012" num="0012"><table frame="all"><title>Table 6:</title><tgroup cols="2" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="left"><b>W / O cream</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Polyglyceryl-3-diisostearates</entry><entry namest="col2" nameend="col2" align="left">3,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="left">3,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyglyceryl-2-dipolyhydroxystearate</entry><entry namest="col2" nameend="col2" align="left">3,50</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative</entry><entry namest="col2" nameend="col2" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100.0</entry></row><row><entry namest="col1" nameend="col1" align="left">Magnesium sulfate</entry><entry namest="col2" nameend="col2" align="left">0,6</entry></row><row><entry namest="col1" nameend="col1" align="left">Isopropyl stearate</entry><entry namest="col2" nameend="col2" align="left">2,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Caprylyl ether</entry><entry namest="col2" nameend="col2" align="left">8,0</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Cetearyl isononanoate</entry><entry namest="col2" nameend="col2" align="left">6,0</entry></row></tbody></tgroup></table></tables>

In an analogous manner, an emulsion was produced using dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 21 (see FIG. 4).

Example 11: Preparation of a cream based on a water-in-oil-in-water emulsion

By mixing the components shown in the table, a cream of the composition likewise given was prepared on the basis of a water-in-oil-in-water dispersion. The oligoribonucleotide used was dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 20 (see FIG. 3). The two strands of the dsRNA each had two 2'-deoxythymidine residues at the 3 'position.<tables id="tabl0013" num="0013"><table frame="all"><title>Table 7:</title><tgroup cols="2" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="left"><b>W / O / W cream</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Glyceryl stearate</entry><entry namest="col2" nameend="col2" align="left">3,00</entry></row><row><entry namest="col1" nameend="col1" align="left">PEG-100 stearate</entry><entry namest="col2" nameend="col2" align="left">0,75</entry></row><row><entry namest="col1" nameend="col1" align="left">Behenyl alcohol</entry><entry namest="col2" nameend="col2" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Caprylic / Capric triglyceride</entry><entry namest="col2" nameend="col2" align="left">8,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Octyldodecanol</entry><entry namest="col2" nameend="col2" align="left">5,00</entry></row><row><entry namest="col1" nameend="col1" align="left">C12-15 alkyl benzoate</entry><entry namest="col2" nameend="col2" align="left">3,00</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-sonic hedgehog dsRNA (consisting of the sequence with the number 17 and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Magnesium sulfate (MgSO4)</entry><entry namest="col2" nameend="col2" align="left">0,80</entry></row><row><entry namest="col1" nameend="col1" align="left">Ethylenediaminetetraacetic acid</entry><entry namest="col2" nameend="col2" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative</entry><entry namest="col2" nameend="col2" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100.0</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">pH adjusted to 6.0</entry><entry namest="col2" nameend="col2" /></row></tbody></tgroup></table></tables>

Example 12: Conditioner Shampoo with Pearlescent

A pearlescent conditioner shampoo was prepared by mixing the components listed in the table. The oligoribonucleotide used was dsRNA, which was obtained by hybridizing SEQ ID No 6 and SEQ ID No 7. The dsRNA inhibits the expression of the growth factor TGFbeta-1 by RNA interference and is referred to as anti-TGFbeta-1 dsRNA (see FIG. 2). The two strands of the dsRNA each had two 2'-deoxythymidine residues at the 3 'position.<tables id="tabl0014" num="0014"><table frame="all"><title>Table 8:</title><tgroup cols="2" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-10</entry><entry namest="col2" nameend="col2" align="left">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Sodium laureth sulfate</entry><entry namest="col2" nameend="col2" align="left">9,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Cocoamidopropyl betaine</entry><entry namest="col2" nameend="col2" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Pearlescent agents</entry><entry namest="col2" nameend="col2" align="left">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative, perfume, thickener, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100.0</entry></row><row rowsep="1"><entry namest="col1" nameend="col2" align="justify">The pH is adjusted to 6.</entry></row></tbody></tgroup></table></tables>

A shampoo was produced in an analogous manner using dsRNA, which was obtained by hybridizing the sense RNA and antisense RNA strand to SEQ ID NO 21 (see FIG. 4).

Example 13: clear conditioner shampoo

<tables id="tabl0015" num="0015"><table frame="all"><title>Table 9:</title><tgroup cols="2" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-10</entry><entry namest="col2" nameend="col2" align="left">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">Sodium laureth sulfate</entry><entry namest="col2" nameend="col2" align="left">9,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Cocoamidopropyl betaine</entry><entry namest="col2" nameend="col2" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-androgen receptor dsRNA (consisting of the sequence with the SEQ ID No and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Folic acid</entry><entry namest="col2" nameend="col2" align="left">0.20</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative, perfume, thickener, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100.0</entry></row><row rowsep="1"><entry namest="col1" nameend="col2" align="justify">The pH is adjusted to 6.</entry></row></tbody></tgroup></table></tables>

Example 14: clear light shampoo with volume effect

<tables id="tabl0016" num="0016"><table frame="all"><title>Table 10:</title><tgroup cols="2" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Sodium laureth sulfate</entry><entry namest="col2" nameend="col2" align="left">9,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Cocoamidopropyl betaine</entry><entry namest="col2" nameend="col2" align="left">2,50</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,10</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative, perfume, thickener, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry></row><row><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100.0</entry></row><row rowsep="1"><entry namest="col1" nameend="col2" align="justify">The pH is adjusted to 5.5.</entry></row></tbody></tgroup></table></tables>

Example 15: Hair treatments

Hair treatments were prepared by mixing the components listed in the table. The oligoribonucleotide used was dsRNA, which was obtained by hybridizing SEQ ID No 6 and SEQ ID No 7. The dsRNA inhibits the expression of the growth factor TGFbeta-1 by means of RNA interference and is referred to as anti-TGFbeta-1 dsRNA (see. Figure 2). The two strands of the dsRNA each had two 2'-deoxythymidine residues at the 3 'position.<tables id="tabl0017" num="0017"><table frame="all"><title>Table 11:</title><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="left"><b>1</b></entry><entry namest="col3" nameend="col3" align="left"><b>2</b></entry><entry namest="col4" nameend="col4" align="left"><b>3</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Hydroxypropylmethyl cellulose</entry><entry namest="col2" nameend="col2" align="left">0,5%</entry><entry namest="col3" nameend="col3" align="left">0,5%</entry><entry namest="col4" nameend="col4" align="left">0,5%</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetrimonium bromide</entry><entry namest="col2" nameend="col2" align="left">1,0</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">0,8</entry></row><row><entry namest="col1" nameend="col1" align="left">Behentrimonium chloride</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">0,7</entry><entry namest="col4" nameend="col4" align="left">0,3</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="left">3,0</entry><entry namest="col3" nameend="col3" align="left">3,0</entry><entry namest="col4" nameend="col4" align="left">3,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetearyl alcohol</entry><entry namest="col2" nameend="col2" align="left">2,5</entry><entry namest="col3" nameend="col3" align="left">2,5</entry><entry namest="col4" nameend="col4" align="left">2,5</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl stearate</entry><entry namest="col2" nameend="col2" align="left">2,0</entry><entry namest="col3" nameend="col3" align="left">2,0</entry><entry namest="col4" nameend="col4" align="left">2,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-10</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Guar hydroxypropyl trimonium chloride</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">0,2</entry><entry namest="col4" nameend="col4" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative, perfume, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100</entry><entry namest="col3" nameend="col3" align="left">ad 100</entry><entry namest="col4" nameend="col4" align="left">ad 100</entry></row></tbody></tgroup></table></tables>

Example 16: Hair conditioners

<tables id="tabl0018" num="0018"><table frame="all"><title>Table 12:</title><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="left"><b>1</b></entry><entry namest="col3" nameend="col3" align="left"><b>2</b></entry><entry namest="col4" nameend="col4" align="left"><b>3</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Cetrimonium chloride</entry><entry namest="col2" nameend="col2" align="left">1,0</entry><entry namest="col3" nameend="col3" align="left">0,5</entry><entry namest="col4" nameend="col4" align="left">0,5</entry></row><row><entry namest="col1" nameend="col1" align="left">Behentrimonium chloride</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">0,2%</entry><entry namest="col4" nameend="col4" align="left">0,3</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="left">3,0</entry><entry namest="col3" nameend="col3" align="left">3,0</entry><entry namest="col4" nameend="col4" align="left">3,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Hydroxyethyl cellulose</entry><entry namest="col2" nameend="col2" align="left">0,2</entry><entry namest="col3" nameend="col3" align="left">0,2</entry><entry namest="col4" nameend="col4" align="left">0,2</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-10</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Guar hydroxypropyl trimonium chloride</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">0,2</entry><entry namest="col4" nameend="col4" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative, perfume, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100</entry><entry namest="col3" nameend="col3" align="left">ad 100</entry><entry namest="col4" nameend="col4" align="left">ad 100</entry></row></tbody></tgroup></table></tables>

Example 17: Leave-on conditioner

<tables id="tabl0019" num="0019"><table frame="all"><title>Table 13:</title><tgroup cols="5" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="31.50mm" /><colspec colnum="2" colname="col2" colwidth="31.50mm" /><colspec colnum="3" colname="col3" colwidth="31.50mm" /><colspec colnum="4" colname="col4" colwidth="31.50mm" /><colspec colnum="5" colname="col5" colwidth="31.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="left"><b>1</b></entry><entry namest="col3" nameend="col3" align="left"><b>2</b></entry><entry namest="col4" nameend="col4" align="left"><b>3</b></entry><entry namest="col5" nameend="col5" align="left"><b>4</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Cetyl alcohol</entry><entry namest="col2" nameend="col2" align="left">1,5</entry><entry namest="col3" nameend="col3" align="left">1,8</entry><entry namest="col4" nameend="col4" align="left">2,0</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Cetrimonium chloride</entry><entry namest="col2" nameend="col2" align="left">0,3</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,5</entry><entry namest="col5" nameend="col5" align="left">0,5</entry></row><row><entry namest="col1" nameend="col1" align="left">Behentrimonium chloride</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">0,2</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Benzophenones</entry><entry namest="col2" nameend="col2" align="left">0,05</entry><entry namest="col3" nameend="col3" align="left">0,03</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">4</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /><entry namest="col5" nameend="col5" /></row><row><entry namest="col1" nameend="col1" align="left">PVP / VA copolymer</entry><entry namest="col2" nameend="col2" align="left">0,4</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-37</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">1,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-4</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,2</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-10</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">0,5</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Panthenol</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">0,2</entry><entry namest="col5" nameend="col5" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Hydroxyethyl cellulose</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,3</entry></row><row><entry namest="col1" nameend="col1" align="left">Acrylates / C10-30 alkyl acrylates crosspolymer</entry><entry namest="col2" nameend="col2" align="left">0,5</entry><entry namest="col3" nameend="col3" align="left">0,3</entry><entry namest="col4" nameend="col4" align="left">0,2</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">C12-13 alkyl lactates</entry><entry namest="col2" nameend="col2" align="left">2,0</entry><entry namest="col3" nameend="col3" align="left">1,0</entry><entry namest="col4" nameend="col4" align="left">1,5</entry><entry namest="col5" nameend="col5" align="left">1,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Laureth-4</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,5</entry></row><row><entry namest="col1" nameend="col1" align="left">Aluminum Starch Octenylsuccinate</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">1,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Dicaprylyl carbonates</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">1,0</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,1</entry><entry namest="col5" nameend="col5" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative, perfume, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry><entry namest="col5" nameend="col5" align="left">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100</entry><entry namest="col3" nameend="col3" align="left">ad 100</entry><entry namest="col4" nameend="col4" align="left">ad 100</entry><entry namest="col5" nameend="col5" align="left">ad 100</entry></row></tbody></tgroup></table></tables>

Example 18: Spray conditioner

<tables id="tabl0020" num="0020"><table frame="all"><title>Table 14:</title><tgroup cols="5" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="31.50mm" /><colspec colnum="2" colname="col2" colwidth="31.50mm" /><colspec colnum="3" colname="col3" colwidth="31.50mm" /><colspec colnum="4" colname="col4" colwidth="31.50mm" /><colspec colnum="5" colname="col5" colwidth="31.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="left"><b>1</b></entry><entry namest="col3" nameend="col3" align="left"><b>2</b></entry><entry namest="col4" nameend="col4" align="left"><b>3</b></entry><entry namest="col5" nameend="col5" align="left"><b>4</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Cetrimonium chloride</entry><entry namest="col2" nameend="col2" align="left">0,2</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,8</entry><entry namest="col5" nameend="col5" align="left">0,5</entry></row><row><entry namest="col1" nameend="col1" align="left">Behentrimonium chloride</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">0,2</entry><entry namest="col4" nameend="col4" align="left">0,3</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Benzophenone-4</entry><entry namest="col2" nameend="col2" align="left">0,05</entry><entry namest="col3" nameend="col3" align="left">0,03</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">PVP / VA copolymer</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">0,7</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-10</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquatium-4</entry><entry namest="col2" nameend="col2" align="left">0,2</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Propylene glycol</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">3,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyquaternium-11</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">0,2</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Panthenol</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">0,2</entry><entry namest="col5" nameend="col5" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Glyceryl isostearate</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,4</entry></row><row><entry namest="col1" nameend="col1" align="left">Isoceteth-20</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,8</entry></row><row><entry namest="col1" nameend="col1" align="left">Dicaprylyl carbonates</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,5</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,1</entry><entry namest="col5" nameend="col5" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Preservative, perfume, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry><entry namest="col5" nameend="col5" align="left">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100</entry><entry namest="col3" nameend="col3" align="left">ad 100</entry><entry namest="col4" nameend="col4" align="left">ad 100</entry><entry namest="col5" nameend="col5" align="left">ad 100</entry></row></tbody></tgroup></table></tables>

Example 19: Hair lotions

<tables id="tabl0021" num="0021"><table frame="all"><title>Table 15:</title><tgroup cols="5" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="31.50mm" /><colspec colnum="2" colname="col2" colwidth="31.50mm" /><colspec colnum="3" colname="col3" colwidth="31.50mm" /><colspec colnum="4" colname="col4" colwidth="31.50mm" /><colspec colnum="5" colname="col5" colwidth="31.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="left"><b>1</b></entry><entry namest="col3" nameend="col3" align="left"><b>2</b></entry><entry namest="col4" nameend="col4" align="left"><b>3</b></entry><entry namest="col5" nameend="col5" align="left"><b>4</b></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Ethanol</entry><entry namest="col2" nameend="col2" align="left">30,0</entry><entry namest="col3" nameend="col3" align="left">50,0</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Isopropanol</entry><entry namest="col2" nameend="col2" align="left">-</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">40,0</entry><entry namest="col5" nameend="col5" align="left">30,0</entry></row><row><entry namest="col1" nameend="col1" align="left">Panthenol</entry><entry namest="col2" nameend="col2" align="left">0,2</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,2</entry><entry namest="col5" nameend="col5" align="left">0,2</entry></row><row><entry namest="col1" nameend="col1" align="left">menthol</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">-</entry><entry namest="col4" nameend="col4" align="left">0,05</entry><entry namest="col5" nameend="col5" align="left">0,05</entry></row><row><entry namest="col1" nameend="col1" align="left">Tocopheryl Acetate</entry><entry namest="col2" nameend="col2" align="left">0,2</entry><entry namest="col3" nameend="col3" align="left">0,2</entry><entry namest="col4" nameend="col4" align="left">-</entry><entry namest="col5" nameend="col5" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">C12-13 alkyl lactates</entry><entry namest="col2" nameend="col2" align="left">0,2</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,2</entry><entry namest="col5" nameend="col5" align="left">-</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-TGFbeta-1 dsRNA (dsRNA from SEQ ID NOs 6 and 7, see FIG. 2)</entry><entry namest="col2" nameend="col2" align="left">0,1</entry><entry namest="col3" nameend="col3" align="left">0,1</entry><entry namest="col4" nameend="col4" align="left">0,1</entry><entry namest="col5" nameend="col5" align="left">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume, pH adjustment and solubilizer</entry><entry namest="col2" nameend="col2" align="left">qs</entry><entry namest="col3" nameend="col3" align="left">qs</entry><entry namest="col4" nameend="col4" align="left">qs</entry><entry namest="col5" nameend="col5" align="left">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="left">ad 100</entry><entry namest="col3" nameend="col3" align="left">ad 100</entry><entry namest="col4" nameend="col4" align="left">ad 100</entry><entry namest="col5" nameend="col5" align="left">ad 100</entry></row></tbody></tgroup></table></tables>

Example 20: Type C aerosol spray

<tables id="tabl0022" num="0022"><table frame="all"><title>Table 16:</title><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">I.</entry><entry namest="col3" nameend="col3" align="center">II</entry><entry namest="col4" nameend="col4" align="center">III</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Aluminum chlorohydrate</entry><entry namest="col2" nameend="col2" align="center">45,00</entry><entry namest="col3" nameend="col3" align="center">45,00</entry><entry namest="col4" nameend="col4" align="center">45,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Isopropyl palmitate</entry><entry namest="col2" nameend="col2" align="center">25,00</entry><entry namest="col3" nameend="col3" align="center">25,00</entry><entry namest="col4" nameend="col4" align="center">25,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Cyclomethicone</entry><entry namest="col2" nameend="col2" align="center">0,30</entry><entry namest="col3" nameend="col3" align="center">0,30</entry><entry namest="col4" nameend="col4" align="center">0,30</entry></row><row><entry namest="col1" nameend="col1" align="left">Isoparafine</entry><entry namest="col2" nameend="col2" align="center">ad 100.00</entry><entry namest="col3" nameend="col3" align="center">ad 100.00</entry><entry namest="col4" nameend="col4" align="center">ad 100.00</entry></row><row><entry namest="col1" nameend="col1" align="left">talc</entry><entry namest="col2" nameend="col2" align="center">10,00</entry><entry namest="col3" nameend="col3" align="center">10,00</entry><entry namest="col4" nameend="col4" align="center">10,00</entry></row><row><entry namest="col1" nameend="col1" align="left">1- (2-ethylhexyl) glycerol ether</entry><entry namest="col2" nameend="col2" align="center">0,50</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Methyl phenylbutanol</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">0,30</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyglyceryl-2-caprate</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-sonic hedgehog dsRNA (consisting of the sequence with the number 17 and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="center">0,1</entry><entry namest="col3" nameend="col3" align="center">0,1</entry><entry namest="col4" nameend="col4" align="center">0,1</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="center">qs</entry><entry namest="col3" nameend="col3" align="center">qs</entry><entry namest="col4" nameend="col4" align="center">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Ethanol</entry><entry namest="col2" nameend="col2" align="center">ad 100.00</entry><entry namest="col3" nameend="col3" align="center">ad 100.00</entry><entry namest="col4" nameend="col4" align="center">ad 100.00</entry></row></tbody></tgroup></table></tables>

The liquid phase obtained by mixing the respective constituents together is filled into an aerosol container with a propane-butane mixture (2: 7) in a ratio of 17:83.

Example 21: Pump atomizer

<tables id="tabl0023" num="0023"><table frame="all"><title>Table 17:</title><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">I.</entry><entry namest="col3" nameend="col3" align="center">II</entry><entry namest="col4" nameend="col4" align="center">III</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Ethanol</entry><entry namest="col2" nameend="col2" align="center">55,00</entry><entry namest="col3" nameend="col3" align="center">55,00</entry><entry namest="col4" nameend="col4" align="center">55,00</entry></row><row><entry namest="col1" nameend="col1" align="left">PEG-40 hydrogenated castor oil</entry><entry namest="col2" nameend="col2" align="center">2,00</entry><entry namest="col3" nameend="col3" align="center">2,00</entry><entry namest="col4" nameend="col4" align="center">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Glycerin</entry><entry namest="col2" nameend="col2" align="center">1,00</entry><entry namest="col3" nameend="col3" align="center">1,00</entry><entry namest="col4" nameend="col4" align="center">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">1- (2-ethylhexyl) glycerol ether</entry><entry namest="col2" nameend="col2" align="center">0,50</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Methyl phenylbutanol</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">0,30</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyglyceryl-2-caprate</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-IGF-1 dsRNA (consisting of the sequence with No. 44 and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="center">1,00</entry><entry namest="col3" nameend="col3" align="center">1,00</entry><entry namest="col4" nameend="col4" align="center">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="center">qs</entry><entry namest="col3" nameend="col3" align="center">qs</entry><entry namest="col4" nameend="col4" align="center">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="center">ad 100.00</entry><entry namest="col3" nameend="col3" align="center">ad 100.00</entry><entry namest="col4" nameend="col4" align="center">ad 100.00</entry></row></tbody></tgroup></table></tables>

Example 22: Roll-on Gel Type A

<tables id="tabl0024" num="0024"><table frame="all"><title>Table 18:</title><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">I.</entry><entry namest="col3" nameend="col3" align="center">II</entry><entry namest="col4" nameend="col4" align="center">III</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Ethanol</entry><entry namest="col2" nameend="col2" align="center">50,00</entry><entry namest="col3" nameend="col3" align="center">50,00</entry><entry namest="col4" nameend="col4" align="center">50,00</entry></row><row><entry namest="col1" nameend="col1" align="left">PEG-40 hydrogenated castor oil</entry><entry namest="col2" nameend="col2" align="center">2,00</entry><entry namest="col3" nameend="col3" align="center">2,00</entry><entry namest="col4" nameend="col4" align="center">2,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Hydroxyethyl cellulose</entry><entry namest="col2" nameend="col2" align="center">0,50</entry><entry namest="col3" nameend="col3" align="center">0,50</entry><entry namest="col4" nameend="col4" align="center">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">1- (2-ethylhexyl) glycerol ether</entry><entry namest="col2" nameend="col2" align="center">0,50</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Methyl phenylbutanol</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">0,30</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyglyceryl-2-caprate</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-IGF-1 dsRNA (consisting of the sequence with No. 44 and the associated complementary sequence strand)</entry><entry namest="col2" nameend="col2" align="center">1,00</entry><entry namest="col3" nameend="col3" align="center">1,00</entry><entry namest="col4" nameend="col4" align="center">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="center">qs</entry><entry namest="col3" nameend="col3" align="center">qs</entry><entry namest="col4" nameend="col4" align="center">qs</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">water</entry><entry namest="col2" nameend="col2" align="center">ad 100.00</entry><entry namest="col3" nameend="col3" align="center">ad 100.00</entry><entry namest="col4" nameend="col4" align="center">ad 100.00</entry></row></tbody></tgroup></table></tables>

Example 23: Antiperspirant stick

<tables id="tabl0025" num="0025"><table frame="all"><title>Table 19:</title><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">I.</entry><entry namest="col3" nameend="col3" align="center">II</entry><entry namest="col4" nameend="col4" align="center">III</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Stearyl alcohol</entry><entry namest="col2" nameend="col2" align="center">25,00</entry><entry namest="col3" nameend="col3" align="center">20,00</entry><entry namest="col4" nameend="col4" align="center">15,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Hydrogenated castor oil</entry><entry namest="col2" nameend="col2" align="center">2,00</entry><entry namest="col3" nameend="col3" align="center">3,00</entry><entry namest="col4" nameend="col4" align="center">4,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Cyclomethicone</entry><entry namest="col2" nameend="col2" align="center">ad 100</entry><entry namest="col3" nameend="col3" align="center">ad 100</entry><entry namest="col4" nameend="col4" align="center">ad 100</entry></row><row><entry namest="col1" nameend="col1" align="left">1- (2-Ethythexyl) glycerol ether</entry><entry namest="col2" nameend="col2" align="center">0,50</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Methyl phenylbutanol</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">0,30</entry><entry namest="col4" nameend="col4" align="center">-</entry></row><row><entry namest="col1" nameend="col1" align="left">Polyglyceryl-2-caprate</entry><entry namest="col2" nameend="col2" align="center">-</entry><entry namest="col3" nameend="col3" align="center">-</entry><entry namest="col4" nameend="col4" align="center">0,50</entry></row><row><entry namest="col1" nameend="col1" align="left">anti-IGF-1 dsRNA (consisting of the sequence with no.</entry><entry namest="col2" nameend="col2" align="center">1,00</entry><entry namest="col3" nameend="col3" align="center">1,00</entry><entry namest="col4" nameend="col4" align="center">1,00</entry></row><row><entry namest="col1" nameend="col1" align="left">Aluminum chlorohydrate, powder</entry><entry namest="col2" nameend="col2" align="center">20,00</entry><entry namest="col3" nameend="col3" align="center">25,00</entry><entry namest="col4" nameend="col4" align="center">25,00</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Perfume</entry><entry namest="col2" nameend="col2" align="center">qs</entry><entry namest="col3" nameend="col3" align="center">qs</entry><entry namest="col4" nameend="col4" align="center">qs</entry></row></tbody></tgroup></table></tables><img file="EP1598421A2_D0026.tif" /><img file="EP1598421A2_D0027.tif" /><img file="EP1598421A2_D0028.tif" /><img file="EP1598421A2_D0029.tif" /><img file="EP1598421A2_D0030.tif" /><img file="EP1598421A2_D0031.tif" /><img file="EP1598421A2_D0032.tif" /><img file="EP1598421A2_D0033.tif" /><img file="EP1598421A2_D0034.tif" /><img file="EP1598421A2_D0035.tif" /><img file="EP1598421A2_D0036.tif" /><img file="EP1598421A2_D0037.tif" /><img file="EP1598421A2_D0038.tif" /><img file="EP1598421A2_D0039.tif" /><img file="EP1598421A2_D0040.tif" /><img file="EP1598421A2_D0041.tif" /><img file="EP1598421A2_D0042.tif" /><img file="EP1598421A2_D0043.tif" /><img file="EP1598421A2_D0044.tif" /><img file="EP1598421A2_D0045.tif" /><img file="EP1598421A2_D0046.tif" /><img file="EP1598421A2_D0047.tif" /><img file="EP1598421A2_D0048.tif" /><img file="EP1598421A2_D0049.tif" />