DE10351149A1 - Oligoribonucleotides for the treatment of unwanted pigmentation of the skin and hair by RNA interference - Google Patents

Abstract

A double-stranded oligoribonucleotide or a physiologically acceptable salt thereof capable of inducing degradation of mRNA from one or more structures involved in the pigmentation of the skin and / or hair.

Description

The The invention relates to oligoribonucleotides which inhibit the degradation of mRNA Enzymes and structures involved in the pigmentation process of the skin induce and in particular for the treatment and prophylaxis undesirable Pigmentation of the skin (skin tanning) are suitable, as occurs for example as a result of UV irradiation. Likewise, the present invention relates to undesirable pigmentation The Hair.

In a preferred embodiment The present invention relates to cosmetic and dermatological Preparations for the prophylaxis and treatment of undesirable Pigmentation, for example local hyper- and false pigmentation (Liver spots, freckles, age spots, melasma, postinflammatory Hyperpigmentation), but also purely the cosmetic whitening larger, the individual skin type in itself quite appropriately pigmented Skin surfaces.

For pigmentation the skin is responsible for the melanocytes, which are in the lowest Layer of the epidermis, the stratum basale, beside the basal cells as - ever Depending on skin type either isolated or more or less frequently occurring - pigment-forming Cells are found. Melanocytes contain as characteristic Cellular melanosomes in which the melanin is formed. Among other things, when excited by UV radiation is increasingly melanin educated. This is about the living layers of the epidermis (keratinocytes) ultimately in the horny layer (corneocytes) transports and calls one more or less pronounced brownish to brown-black skin. Melanin is used as the final stage of a formed oxidative process in which tyrosine with participation the enzyme tyrosinase over several intermediate stages to the brown to brown-black Eumelaninen (DHICA and DHI melanin) or with the involvement of sulfur-containing Connections to the reddish pheomelanin is converted. DHICA and DHI melanin are produced via the common intermediates dopaquinone and dopachrome. The latter becomes partially involving other enzymes, either in indole-5,6-quinone carboxylic acid or converted into indole-5,6-quinone, from which the two mentioned eumelanins arise. The genesis of phaeomelanin runs under over the intermediates dopaquinone and cysteinyldopa. Is controlled the expression of the melanin-synthesizing enzymes by a specific transcription factor (microphthalmia-associated transcription factor, MITF). In addition to the described enzymatic processes of Melanin synthesis are other melanogenesis proteins in melanosomes significant. An important role seems to be the so-called p-protein, the exact function is still unclear.

Next the previously described process of melanin synthesis in the melanocytes, pigmentation of the skin is also the transfer of the melanosomes, their whereabouts in the epidermis as well as their degradation and degradation of melanin vital. It could be shown that for transport of melanosomes from melanocytes into keratinocytes the PAR-2 receptor is important (Seiberg M. et al., 2000, J. Cell. Sci., 113: 3093-101). Furthermore, the size and shape of the melanosomes Influence on their light-scattering properties and thus the color Appearance of the skin. For example, in black Africans we find increasingly large spheroidale, individually present melanosomes, while in Caucasians rather smaller, is found in groups of melanosomes.

• • am eigentlichen Melanin-Synthseprozess in den Melanosomen (Tyrosianse, TRP-1, TRP-2, p-Protein)
• • am Transfer/an der Verteilung der Melanosomen an die benachbarten Zellen, insbesondere Keratinozyten (PAR-2) sowie
• • an der Expression der o.g. Strukturen (insbesondere über den Transkriptionsfaktor MITF)

beteiligt sind.Basically, one can thus differentiate in the pigmentation of the skin structures that

• • the actual melanin synthesis process in the melanosomes (tyrosian, TRP-1, TRP-2, p-protein)
• • on the transfer / distribution of melanosomes to neighboring cells, especially keratinocytes (PAR-2) as well as
• • on the expression of the above-mentioned structures (in particular via the transcription factor MITF)

involved.

issues with hyperpigmentation of the skin have many causes or are concomitant many biological processes, e.g. UV radiation (e.g., freckles, ephelides), genetic disposition, False pigmentation of the skin during wound healing or scarring (postinflammatory hyperpigmentation) or skin aging (e.g., Lentigines seniles).

Active ingredients and preparations are known which counteract skin pigmentation. In practical use are essentially preparations based on hydroquinone, but some of which only after several weeks of application show their effect, their exaggerated use of other On the other hand, it is questionable for toxicological reasons. By Albert Kligman et al. a so-called triformula was developed, which represents a combination of 0.1% tretinoin, 5.0% hydroquinone, 0.1% dexamethasone (A. Kligman, 1975, Arch. Dermatol., 111: 40-48). However, this formulation is also very controversial because of possible irreversible changes in the pigmentation system of the skin. Also, the use of mercury compounds is common, which is also toxicologically highly questionable. In addition, peel-off methods (chemical and mechanical "peelings") are used, which, however, often lead to inflammatory reactions and can even lead to stronger rather than reduced pigmentation due to postinflammatory hyperpigmentation.

In The cosmetics are besides skin health and skin care as well the hair care an extremely intense explored area.

hair is made of horn, thread-shaped, almost universal (an Palms, Soles, Extensor sides of the toe, finger end limbs missing) Appendices; distinguished as longhair (the head, beard, underarm, pubic hair = Capilli, Barba, Hirci or Pubes; in the man also chest hair), short, Bristle hair (Supercilia, Cilia, Vibrissae, Tragi) and wool hair (Lanugo, Vellus). The structure of all these hairs is roughly similar: central hairmark (from epithelial cells with eosinophilic horny substance granules = trichohyalin granules), surrounded by the hair rind (from keratinized cells, contains pigments) and the hair cuticle (Cuticle pili, seedless epidermis layer) and layers of the Epithelial and connective tissue hair sheath.

The Hair is divided into the protruding from the skin hair shaft and the in the subcutis reaching, oblique Hair root, whose layers correspond approximately to those of the epidermis. The thickened lower end of the root, the hair bulb, sits in one she protruding, vessel-containing Connective tissue cones, the hair papilla, on (both as hair growth). The Onion is bulbous in the initial (= anagen) phase of cyclically repeating hair formation layered as a result of constant New formation of cells through their papillary layer (matrix), later then closed, kolbig, completely horny (piston hair) and finally, in the end (= telogen) phase, starting with a new hair from a newly forming hair papilla - displaced towards follicle opening.

Responsible for the personal Hair color is the melanin. The melanin is formed in the melanocytes, Cells that are in the hair bulb associated with the keratinocytes of the hair park. Melanocytes contain as characteristic Cellular melanosomes in which the melanin is formed. This is about the long dendrites of the melanocytes into the keratinocytes of the precortical Matrix transfers and calls the more or less pronounced blonde to brown-black hair color. The processes of melanin synthesis and the distribution of melanin in the hair done analogously the processes described above.

The Eumelanin is the black and brown pigment. It is crucial mainly about the Color depth of the hair. In brown and black hair it comes in clearly recognizable granules in front.

• • Blondes Haar enthält wenig Eumelanin und viel Phaeomelanin.
• • Dunkles Haar enthält viel Eumelanin und wenig Phaeomelanin.
• • Rotes Haar hat ebenfalls wenig Eumelanin und sehr viel Phaeomelanin.
• • Alle dazwischenliegenden Haarschattierungen entstehen aus unterschiedlichen Mischungsverhältnissen der beiden Melanintypen.

Phaeomelanin is the red pigment. It is responsible for blond, blonde and red hair. This melanin is much finer and smaller in structure. The different proportions of the melanin types give rise to the different hair colors:

• • Blond hair contains little eumelanin and a lot of phaeomelanin.
• • Dark hair contains a lot of eumelanin and little phaeomelanin.
• • Red hair also has little eumelanin and a lot of phaeomelanin.
• • All intervening hair shades arise from different mixing ratios of the two melanin types.

Expire the pigmentation process can only if enough Tyrosinase available stands. This enzyme is less frequently formed with increasing age. Leading then gradually gray hair. The reason: with little tyrosinase less and less tyrosine is being formed. So does the production from melanin. The missing melanin is due to the storage of air bubbles replaced. The hair appears gray.

This Process is usually insidious. He starts at the temples and then expands on the entire head hair. After that caught it's the beard and the eyebrows. Finally, all hair is finally of the body Gray.

Medical Gray hair is called Canities. There are different options of the grave. Premature graying, from the age of 20, calls also Canities praecox.

• • Perniziöse Anämie (Vitamin-B-Mangelanämie),
• • schwere endokrinologische Störungen, z. B. bei Schilddrüsenerkrankungen.
• • akute, fieberhafte Erkrankungen,
• • Arzneimittelnebenwirkungen,
• • Kosmetika,
• • Metalle.

The canary symptomatica, or symptomatic graying of the hair, can have different causes. This includes:

• • Pernicious anemia (vitamin B deficiency anemia),
• • severe endocrine disorders, eg. B. in thyroid disease.
• • acute, feverish illness,
• • drug side effects,
• • cosmetics,
• • metals.

The coloring of hair, especially of living human hair, with the help of natural dyes, as has been known since ancient times in particular for the dye henna is, and for years in favor of synthetic dyes in the Background urged have been the subject of a new interest for some years. The disadvantage is the henna resulting red hue.

With Increasing age decreases the melanin production, which the Hair color causes: the hair turns gray or white. It is a cosmetic desire among some consumers, this process to reverse or slow down. For this purpose uses the cosmetic industry in some countries lead acetate, which is toxic is and therefore in the European Cosmetics Regulation is prohibited. This lead acetate is preferably as a solution applied to the hair and remains there for a long time without being washed off to become.

For dyeing keratin-containing fibers, eg. As hair, wool or fur, come generally either direct dyes or oxidation dyes, by oxidative coupling of one or more developer components arise with each other or with one or more coupler components, for Application. Coupler and developer components are also known as oxidation dye precursors designated.

When Developer components are commonly used primary aromatic amines with another, in para or ortho position free or substituted hydroxy or amino group, Diaminopyridine derivatives, heterocyclic hydrazones, 4-aminopyrazolone derivatives and 2,4,5,6-tetraaminopyrimidine and its derivatives used.

Specific Representatives are, for example, p-phenylenediamine, p-toluenediamine, 2,4,5,6-tetra, p-aminophenol, N, N-bis (2-hydroxyethyl) -p-phenylenediamine, 2- (2,5-diaminophenyl) ethanol, 2- (2,5-diaminophenoxy) ethanol, 1-phenyl-3-carboxamido-4-amino-pyrazolone-5,4-amino-3-methylphenol, 2-aminomethyl-4-aminophenol, 2-hydroxymethyl-4-aminophenol, 2-hydroxy-4,5,6-triaminopyrimidine, 2,4-dihydroxy-5,6-diaminopyrimidine and 2,5,6-triamino-4-hydroxypyrimidine.

When Coupler components are usually m-phenylenediamine derivatives, Naphthols, resorcinol and resorcinol derivatives, pyrazolones and m-aminophenols uses. In particular α-naphthol are suitable as coupler substances, 1,5-, 2,7- and 1,7-dihydroxynaphthalene, 5-amino-2-methylphenol, m-aminophenol, resorcinol, resorcinol monomethyl ether, m-phenylenediamine, 2,4-diaminophenoxyethanol, 1-phenyl-3-methyl-pyrazolone-5, 2,4-dichloro-3-aminophenol, 1,3-bis- (2,4-diaminophenoxy) -propane, 2-chlororesorcinol, 4-chlororesorcinol, 2-chloro-6-methyl-3-aminophenol, 2-methylresorcinol and 5-methylresorcinol.

Regarding other usual ones Dye components becomes explicit to the series "Dermatology", issued by Ch. Culnan, H. Maibach, Marcel Dekker Inc., New York, Basel, 1986, Vol. 7, Ch. Zviak, The Science of Hair Care, ch. 7, pages 248-250 (Direct Dyeing), and Chap. 8, pages 264-267 (oxidation dyes), as well as the "European Inventory of cosmetic raw materials ", 1996, published by the European Commission, available in Diskette form of the Federal Association of German industrial and commercial enterprises for medicines, Health food and personal care products e.V., Mannheim.

Although intensive dyeings with good fastness properties can be obtained with oxidation dyes, the development of the color is generally carried out under the influence of oxidizing agents such. H ₂ O ₂ , which in some cases may result in damage to the fiber. Furthermore, some oxidation dye precursors or certain mixtures of oxidation dye precursors can sometimes have a sensitizing effect on persons with sensitive skin. Direct dyes are under However, their disadvantage lies in the fact that the dyeings often have only insufficient fastness properties.

Object of the present invention is to reduce the autonomous melanin production of the hair, but without dyeing agents and in particular oxidizing agents such. B. H ₂ O ₂ instructed to be. In addition, the funds should have no or only a very low sensitization potential.

Fire et al., Trends Genet. 15 (1999) 358-363 have shown that the Gene expression posttranscriptional due to the presence of double-stranded RNA fragments (dsRNA) homologous to the sequence of the mRNA of the tested gene is, inhibits, and referred to this process as RNA interference (RNAi). The dsRNA causes still unclarified Way the specific degradation of homologous mRNA in the cell and prevents so the protein production.

The WO 01/29058 discloses the identification of genes involved in RNAi and their use for modulating RNAi activity.

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

Out WO 01/68836 is the reduction of gene expression in cells known by dsRNA. The dsRNA contains a nucleotide sequence that under the physiological conditions of the cell with the nucleotide sequence at least part of the gene to be inhibited hybridizes. The dsRNA preferably has a length from 400 to 800 nucleotides.

The WO 01/75164 discloses the use of dsRNA of length 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, the synthesis of siRNAs in mammalian cells trigger and thus to inhibit gene expression of a target gene.

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

The WO 02/053773 relates to an in vitro method for the determination of Skin stress and Skin aging in humans and animals, to carry out the Method suitable test kits and biochips and a test method to prove the efficacy of cosmetic or pharmaceutical Active ingredients against skin stress and Skin aging.

The WO 01/58918 A2 describes the use of oligonucleotides against Tyrosinase and TRP-1 for the lightening of the skin.

oligoribonucleotides dedicated to the prophylaxis and treatment of unwanted pigmentation of the skin and hair, has not previously been described.

task The present invention is the provision of compositions, which is an effective treatment for and prophylaxis against unwanted Pigmentation of the skin and hair, especially against irregular pigmentation of the skin ("uneven skin tone, age spots, melasma etc.), without the disadvantages of the prior art.

following will be involved in the pigmentation of the skin and hair Enzymes and proteins also summarize "at the pigmentation (of Skin and Harren) involved structures ".

It has for The person skilled in the art unpredictably found that a double-stranded oligoribonucleotide or a physiologically acceptable Salt thereof, which is capable of degrading mRNA from one or more several involved in the pigmentation of the skin and / or hair Induce structures that are deficient of the prior art helps.

at the oligoribonucleotides according to the invention they are RNA molecules (RNAs), which suppress the expression of these enzymes in whole or in part (Genabschaltung, Genesilencing), presumably due to the breakdown of mRNA by one attributable to the above enzymes. This process is called RNA interference (RNAi). The invention thus relates to oligoribonucleotides, the degradation of the mRNA of induce the pigmentation of skin or hair involved structures can. The mRNA whose degradation is to be effected will also be discussed below Called target mRNA. According to us, under target gene the gene and in particular the coding part of the gene understood, its expression completely or partially suppressed becomes. Unless otherwise stated, the term target sequence refers to both to the target gene and to the target mRNA. The dismantling of mRNA from participating in the pigmentation of the skin and hair Structures by RNAi runs sequence specific, i. an oligoribonucleotide inhibits in the Usually only the expression of the corresponding target gene.

When Target sequence for the oligoribonucleotides according to the invention the coding regions (cDNA) of the respective genes are preferred, including 5'- and 3'-UTR areas. Especially preferred are the regions of the coding regions that are 50 to 100 nucleotides downstream of the start codon lie.

The oligoribonucleotides according to the invention preferably double-stranded RNA molecules (dsRNAs) which is homologous to the sequence of the target gene, or a portion thereof are, i. in terms of sense and antisense strand to the target gene.

homology is according to the invention then given if the dsRNA is not completely identical to the target sequence is. However, the invention also relates to longer nucleotide fragments, such as e.g. dsRNAs that are in your length correspond to the respective target mRNAs or cDNAs. These may e.g. by soluble Drosophila embryo extract can be transformed into fragments of 21 to 23 nucleotides in length (see WO 01/75164). Long-chain dsRNA also becomes too short intracellularly pieces reduced. However, the direct use of long-chain dsRNA is generally not preferred since these are non-specific in mammalian cells Can cause inhibition of translation.

By This very selective approach does not overlap with other physiological processes in the skin. There are completely clear target proteins whose formation is highly selectively prevented. The only task of these proteins is pigmentation (melanin synthesis) and thus the coloring in skin and hair. Other physiological functions are not known. It is therefore a) a biological objective that no overlap with other biological processes in the skin, b) a technique which selectively deactivates only pigmentation processes. This conditionally especially an extremely low side effect rate - this is theoretically zero - one unusual high efficiency and excellent effectiveness. The unwanted Side effects of classic skin whiteners (hydroquinone, mercury salts etc.) do not occur.

It it was further found that it it is preferred if the pigmentation of the skin and / or the Hair structures involved in (I) the actual melanin synthesis (Melanosomenstrukturen) and / or at the (II) expression of these melanosomal structures and / or involved in the (III) transfer of the melanosomes (into the keratinocytes) are. This has the advantage of a particularly effective effect. The Pigmentation of the skin and hair can be rough in the three processes I-III be divided. The more you inhibit individual steps all the more the overall result is better, as the individual effects multiply.

Therefore It is preferred when participating in the actual melanin synthesis structure involved the enzyme tyrosinase, TRP1, TRP2 or the p-protein is. As a result, the formation of melanin is, so to speak, "nipped in the bud", since tyrosinase is the pacemaker enzyme of melanin formation. TRP1, TRP2 as well in particular, p-protein have a rather supportive function in this context in melanin formation. The prior art, however, is only the inhibition of the already existing pacemaker enzyme tyrosinase by more or less specific inhibitors (kojic acid, etc.). In contrast to this the siRNA approach is highly selective.

The enzymes involved in melanin synthesis are the following oxidases / tautomerases tyrosinase p14679 (EC 1.14.18.1) TRP-1 p17643 (EC 1.14.18.-) TRP-2 P40126 (EC 5.3.3.12)

Tyrosinase (Tyr, Tyro) is the pacemaker enzyme of melanin synthesis. The enzymes TRP-1 (tyrosinase related peptide 1, Tyrp1, Tyr1) and TRP-2 (tyrosinase related peptide 2, Dct, Tyr2) control the extent to which the brown DHICA or, exclusively under the influence of tyrosinase, the black DHI melanin is formed. The figures given are the Accession Numbers of the Swiss-PROT database of the EMBL-EBI (European Bioinformatics Institute Heidelberg).

Also it is preferred if those involved in the expression of melanin synthesis involved structure of the transcriptin factor MITF. this causes an inhibition of the expression of the pacemaker enzyme tyrosinase, which does not expire without the transcription factor MITF, as it has i.a. the expression the tyrosinase controls. Moreover, MITF is - in fact MITF-M - um a very exclusive transcription factor that is only relevant to pigmentation Gene in the skin controls. This in turn has the advantages that the melanin formation very early banned in the bud, b) no side effects occur because it does not interfere with other metabolic pathways, as they do in the case of inhibition "more general Transcription factors "such as e.g. p53, NFkB or AP1 occurred, partially involved in the regulation of pigmentation are.

Other highly preferred structures that influence melanogenesis include the transcription factor MITF and in particular the melanocyte-specific M isoforms (MITF-M) and, in particular, the p-protein (OCA2):
MITF (ID 075030)
MITF-M1 (ID 075030-9)
MITF-M2 (ID 075030-10)
and particularly
P protein (ID Q04671).

stated Here are the Accession Numbers of the Swiss-PROT Database of the EMBL-EBI (European Bioinformatics Institute Heidelberg).

Furthermore, the further preferred structures which influence the pigmentation processes in the skin include those structures which are involved in the transport of the melanosomes into the epidermis. These include the peptidases trypsin and trypsin-like enzymes and various serine proteases (eg mast cell tryptase beta III (ID Q96RZ7; MMCP-7-like tryptase (ID Q996RZ7)).
PAR-2 human (ID P55085)

stated Here is the Accession Numbers of the Swiss-PROT database EMBL-EBI (European Bioinformatics Institute Heidelberg).

Therefore it is particularly preferred when the on the transfer of melanosomes involved structure of Proteinase Activated Receptor 2 (PAR-2) is. In the prior art, in which by inhibition of skin proteases over classic Protease inhibitors PAR-2 is deactivated, no melanin is transported and as a result, the melanin synthesis comes to a standstill. simultaneously becomes by the inhibition of the proteases their important functions in the skin, causing side effects. On the other hand It comes from highly selective switching off PAR-2, the first is not formed, to no influence on the proteases (Desquamation etc.), which continue to perform their physiological functions. Nevertheless is the melanin transport suppressed, because there is no or less PAR-2. This leads to a Skin whitening without side effect.

The pharmaceutical according to the invention or cosmetic compositions preferably contain 0.00001 to 10 wt .-%, particularly preferably 0.0003 to 3 wt .-% and completely particularly preferably 0.01 to 1.0 of the oligoribonucleotide or oligotides according to the invention, based on the total weight of the composition. When using of oligorhinonucleotides integrated into vectors the above quantity is based on the mass of the vector integrated into the vector Oligoribonukleotide, the mass of the vector itself is not considered.

According to the invention, preference is given to those compositions which contain exclusively those oligoribonucleotides which inhibit the expression of one or more of the abovementioned genes, ie the genes of structures involved in the skin pigmentation and, if appropriate, of the proteinase PKR and in particular of the preferred genes mentioned. The compositions of the invention may contain one or preferably more oligoribonucleotides. These may be oligoribonucleotides that inhibit the expression of several different structures involved in skin pigmentation. But it can also be used mixtures of Oligoribonukleotiden, the different sequence areas and the target the same gene or mRNA of a structure involved in skin pigmentation. Preference is given to compositions which contain 1 to 5 and in particular 1 to 3 different oligoribonucleotides. Mixtures of oligoribonucleotides which, in addition to the abovementioned structures involved in the skin pigmentation and optionally the proteinase PKR, non-specifically inhibit or induce the activity of a large number of other skin proteins are undesirable because virtually no control of side effects is possible. By skin proteins are meant those proteins that are expressed in the skin. Very particular preference is given to compositions which contain one or more oligoribonucleotides which inhibit the expression of the tyrosinase or the transcription factor MITF. In particular, the splice variants MITF-M1 and MITF-M2 should be mentioned.

Especially Preference is furthermore given to compositions which are each at least contain an oligoribonucleotide directed against PAR-2.

Further are particularly preferred compositions, each at least contain an oligoribonucleotide that binds against TRP1 and / or TRP-2 is directed.

According to the invention are still those compositions particularly preferred, the oligoribonucleotides which are capable of expression of serine proteinases, such as pancreatic and neutrophilic elastases and macrophage elastase, to inhibit, which belong to the group of elastases.

These Serine proteinases are i.a. involved in phagocytic processes, on the defense against microorganisms, the degradation of elastin, Collagens, proteoglycans, fibrinogen and fibrin, and the digestion of damaged tissues, can but also lead to activation of PAR-2 (Bolognesi, M., K. Djinovic-Carugo, et al. (1994). "Molecular bases for human leucocyte elastase inhibition. "Monaldi Arch Chest Dis 49 (2): 144-9).

According to the invention are such Oligoribonukleotide prefers the expression of the respective Target gene compared to untreated cells by at least 25%, preferably at least 50%, more preferably at least 80%, and most preferably inhibit by at least 85%. If necessary, expression is measured to measure inhibition of the target gene in the cells first induced in a suitable manner. To determine the effectiveness of oligoribonucleotides according to the invention Preferably tumoral cells are used. In the same way can suitable primary cultures be used. The oligoribonucleotides are introduced into the cells and subsequently, optionally after induction of expression of the target gene, the expression rate of the target gene in these cells and compared to that which is found in cells that are not with the respective oligoribonucleotide were transfected.

Also it is preferred if the oligoribonucleotide before the target sequence based on a length of 20 base pairs in a maximum of 0 to 2 base pairs, more preferably 0 to 1 and most preferably no deviations from the target sequence, i. there are a maximum of 0 to 2 and in particular a maximum of 0 to 1 base pairs exchanged for other base pairs. This has the advantage of a special effectiveness, because these with the degree of agreement increases with the target sequence.

Also it is preferred if the length is from 15 to 49 base pairs, preferably 17 to 30, more preferably a length of 19 to 25 base pairs, very particularly preferably 19 to 23 base pairs, very unusual 19 base pairs.

Also it is preferred if the oligoribonucleotide is homologous to a section of the gene involved in the pigmentation of the skin and / or hair Structure is its sense strand 5'-sided by two adenosine residues and 3'-sided through two thymidine residues or by a thymidine and a cytosine residue flanked. This flanking leads to a special effectiveness, without that an explanation would be known. It is particularly preferred if the oligoribonucleotide on 3'-end carries two deoxythymidine residues.

The RNA duplexes according to the invention may have blunt ends or sticky ends. Double-stranded oligoribonucleotides which have an overhang of 1 to 6, preferably 1 or 2, nucleotides at the 3 'end of each strand have proven to be particularly effective. The supernatant nucleotides are preferably 2'-deoxynucleotides, more preferably 2'-deoxythymidine radicals. The use of 2'-deoxynucleotides can reduce the cost of RNA synthesis and increase the resistance of RNA to nuclease degradation. The protruding nucleotides need not necessarily be and remain the nucleotides homologous to the target sequence therefore disregarded in the deviations from the target sequence as 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 portion of the target gene and in particular the corresponding double-stranded cDNA whose sense strand has 5'-side by two adenosine residues (A) and 3'-sided by two thymidine residues (T) or have proved particularly effective a thymidine and a cytidine residue (C) is limited. The section bounded by AA and TT or AA and TC preferably has a length of 19 to 21, in particular 19 nucleotides and thus has the general form AA (N _19-21 ) TT or AA (N _19-21 ) TC, where N stands for a nucleotide. More preferred are oligoribonucleotides which are complementary to a portion of the target gene or the corresponding double-stranded cDNA having the general form AA (N ₁₉ ) to AA (N ₂₁ ). Here, oligoribonucleotides homologous to the N _19-21 fragment of said regions are particularly preferred. The particularly preferred oligoribonucleotides thus have a length of from 19 to 21 base pairs, the single strands forming these oligoribonucleotides preferably having two additional 2'-deoxynucleotides, in particular two 2'-deoxythymidine residues, on the 3'-side, so that the dsRNA has 19 to 21 base pairs and per strand comprises two supernatant 2'-deoxynucleotides.

If the target gene does not contain a region of the form AA (N _19-21 ), look for regions of the form NA (N _19-21 ) or any fragment of the form N _19-21 . Although N _19-21 fragments bounded, for example, by AA and TT are preferred, in principle all dsRNA fragments which are homologous to the target sequence are suitable according to the invention. The oligoribonucleotides according to the invention could advantageously also be integrated into expression vectors, in particular those which bring about expression of the oligoribonucleotides in mammalian cells. In this way, even in the case of intracellular degradation of the oligoribonucleotides, stable inhibition of the expression of the target gene can be achieved since oligoribonucleotides are constantly replenished by 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., Supra. Preference is given to mammalian expression vectors, in particular those which are 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 reverse-complementary to the dsRNA according to the invention and serves as a spacer , and contain a termination signal of 5 consecutive thymidine residues. The vectors thus contain 5 to 9 copies of the respective dsRNA molecule. These may be dsRNAs specific for 1 target gene or dsRNAs specific for several different target genes.

The oligoribonucleotides according to the invention can in the form of unmodified oligoribonucleotides. Preferably However, these are oligoribonucleotides that are at the level the sugar residues, the nucleobases, the phosphate groups and / or the intervening skeletons be chemically modified, for example the stability the oligoribonucleotides in cosmetic or dermatological preparations and / or increase in the skin, e.g. across from a nucleolytic degradation to the penetration of the oligoribonucleotides to improve the skin and the cell to increase the effectiveness of Oligoribonucleotides favorable to influence and / or the affinity to be hybridized Sequence sections to improve.

Prefers are oligoribonucleotides in which one or more phosphate groups by phosphothioate, methylphosphonate and / or phosphoramidate groups, such as. N3 '→ P5' 'phosphoramidate groups, exchanged are. Particularly preferred are oligoribonucleotides in which phosphate groups are replaced by phosphothioate groups. It can be a or more of the phosphate groups of the oligoribonucleotide modified be. In a partial modification preferably terminal groups modified, oligoribonucleotides containing all phosphate groups are modified, but are particularly preferred. This applies mutatis mutandis to the im following modifications described.

preferred Sugar modifications involve the replacement of one or more Ribosereste of Oligoribonukleotids by morpholine rings (Morpholine Oligoribonukleotide) or by amino acids (Peptide-oligoribonucleotides). Preferably, all Ribosereste of Oligoribonukleotids against amino acid residues and in particular morpholine residues replaced.

Especially preferred are morpholine oligoribonucleotides in which the morpholine residues on

Sulfonyl or preferably phosphoryl groups are connected together, as can be seen in formula 1 or 2:
B is a modified or unmodified purine or pyrimidine base, preferably adenine, cytosine, guanine, or uracil,
X is O or S, preferably O,
Y is O or N-CH ₃ , preferably O,
Z is alkyl, O-alkyl, S-alkyl, NH ₂ , 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.

The Formulas 1 and 2 each represent only a portion of an oligoribonucleotide chain represents.

Very particular preference is given to morpholine oligoribonucleotides in which the morpholine radicals are linked to one another via phosphoryl groups, as shown in formula 2, in which X is O, Y is O and Z is N (CH ₃ ) ₂ .

Furthermore, the ribose residues can be modified by amino, such as NH ₂ , fluorine, alkyl or O-alkyl groups, such as OCH ₃ , with 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 acts in the cell Activation of protein kinase PKR counteracting double-stranded RNA dependent is. This is a nonspecific inhibition of translation avoided. Substitution is particularly suitable for this purpose at least one 2'-hydroxyl group the nucleotides of the dsRNA through a 2'-amino or a 2'-methyl group. Furthermore, at least one Nucleotide in at least one strand of the dsRNA be replaced by a so-called "locked nucleotide", the contains a chemically modified sugar ring. A preferred modification of the sugar ring is a 2'-O, 4'-C-methylene bridge. dsRNA, the multiple "locked nucleotides "is prefers.

If unless otherwise stated herein alkyl is preferably linear, branched or cyclic alkyl groups of 1 to 30, preferably 1 to 20, more preferably 1 to 10 and most preferably 1 to 6 carbon atoms. Branched and cyclic radicals naturally have at least 3 carbon atoms, wherein cyclic radicals having at least 5 and in particular at least 6 carbon atoms are preferred.

Also it is preferred if the oligoribonucleotides one or more alpha-nucleosides contain. This makes the siRNA more stable and thus more effective.

Suitable base modifications are, for example, in the US 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, NH ₃ and N _{3 has} proved to be advantageous.

The synthesis of modified and unmodified oligoribonucleotides and other suitable modification possibilities are described in the literature. In addition, the production is modified and not mo In the meantime, it has also been offered as a service by numerous companies, eg Dharmacon, 1376 Miners Drive # 101, Lafayette, CO 80026, USA, Xeragon Inc., Genset Oligos and Ambion. The production of oligoribonucleotides is also described in the US 5,986,084 described.

The The invention also encompasses a pharmaceutical or cosmetic composition containing one or more of the described oligoribonucleotides or a physiologically acceptable Salt thereof and a corresponding composition for topical Application.

Prefers it is when such a composition has multiple oligoribonucleotides contains the expression of several different at the pigmentation inhibit structures involved in skin and / or hair.

Also it is preferred if such a composition comprises a plurality of oligoribonucleotides contains that different sequence regions of the same gene at the actual melanin synthesis (melanosome structures, tyrosis, TRP-1, TRP-2, p-protein) and / or expression of these melanosome structures (MITF) and / or the transfer of the melanosomes (into the keratinocytes) involved structure (PAR-2).

The Oligoribonucleotides and compositions are suitable for treatment and prophylaxis of unwanted Pigmentation of the skin and hair, especially those described above Symptoms. They are suitable for cosmetic and therapeutic treatment from unwanted Pigmentation caused by endogenous and exogenous factors, in particular UV radiation are caused. The compositions of the invention can Prevent pigmentation defects and existing (defective) pigmentation permanently and without the risk of side effects. For determination the effectiveness of the oligoribonucleotides according to the invention For example, the method described in WO 02/053773 be used.

The oligoribonucleotides according to the invention are particularly suitable for the prevention and treatment of unwanted Pigmentation of the skin, as in the form of chronic sun-damaged skin (Age spots, "uneven skin tone "), but also occurs in freckles and melasma. In an equally preferred Form are the Oligoribonukleotide invention Prevention and treatment of sun exposure as well as skin tanning also for lightening the pigmentation of the hair. Likewise is suitable the oligoribonucleotides according to the invention for lightening a pigmentation which is in itself appropriate to the skin type.

On Because of their prophylactic effect, the oligoribonucleotides and Compositions also excellent for skin care.

Such Compositions can preferably in the form of a solution, Cream, ointment, lotion, hydrodispersion, lipodispersion, emulsion, Pickering emulsion, gel, solid stick or aerosol available.

According to the invention are compositions preferred for topical application. The compositions can be used in are present in all galenic forms, usually for a topical one Application can be used, e.g. as a solution, cream, ointment, lotion, Shampoo, that is Emulsion of the water-in-oil type (W / O) or oil-in-water type (O / W), multiple emulsion, for example of the water-in-oil-in-water (W / O / W) type, or oil-in-water-in-oil (O / W / O), Hydrodispersion or lipodispersion, Pickering emulsion, gel, solid Pen or aerosol.

The cosmetic or medical treatment of said indications is usually carried out by single or repeated application of the compositions of the invention on the skin, preferably on the affected skin.

Of the Compositions of the invention are suitable for cosmetic and therapeutic, i. especially dermatological application.

The invention further comprises the use of an oligoribonucleotide or a physiologically acceptable salt thereof or a described preparation for skin care or cosmetic or therapeutic treatment of unwanted pigmentation of the skin or hair and for the production of egg ner cosmetic or therapeutic composition for topical application and skin care or treatment of unwanted pigmentation of the skin or hair and for the treatment of changes or damage to the pigmentation of the skin or hair caused by UV radiation in the skin, dryness , Roughness and slackness of the skin, wrinkling, decreased fatigue by sebaceous glands, and an increased susceptibility to mechanical stress (cracking), for the treatment of photodermatoses, the symptoms of senile xerosis, photoactivation and a degradation of the connective tissue of the skin with unwanted pigmentation of the skin or hair.

The Omitting a single ingredient interferes with the unique properties the overall composition. Therefore, all specified ingredients the preparations according to the invention necessarily to carry out the invention.

to increase stability and / or penetration the oligoribonucleotides are also used in encapsulated form, for example, encapsulated in liposomes. In addition, they can by the addition of Cyclodextrins are stabilized.

cyclodextrins are also called cycloamyloses and cycloglucans. It deals The cyclodextrins are cyclic oligosaccharides from α-1,4 linked Glucose units. As a rule, six to eight glucose units (α-, β- or γ-cyclodextrin) connected with each other. Cyclodextrins are produced by the action of Bacillus macerans on strength receive. They have a hydrophobic interior and a hydrophilic interior Outside. Both are according to the invention the cyclodextrins themselves, especially α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, as well as derivatives thereof.

According to the invention the one or more cyclodextrins in cosmetic and dermatological Compositions preferably in a concentration of 0.0005 to 20.0 wt .-%, in particular 0.01 to 10 wt .-% and particularly preferably used in a concentration of 0.1 to 5.0 wt .-%.

It is advantageous according to the invention use native, polar and / or non-polar substituted cyclodextrins. These include preferably but not exclusively methyl, especially random methyl-β-cyclodextrin, Ethyl and hydroxypropyl cyclodextrins, for example hydroxypropyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin. The invention particularly preferred cyclodextrin species are γ-cyclodextrin and hydroxypropyl-β-cyclocodextrin. Likewise according to the invention particularly preferred are polar cyclodextrins.

liposomes can be in a known manner using natural Phospholipids, e.g. Phosphatidylcholine from eggs, soybeans etc., or synthetic phospholipids (see G. Betageri (Editor), "Liposomes Drug Delivery Systems ", Lancaster Techonomic Publishing Company 1993; Gregoriadis (Editor), "Liposomes 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 counteract a dissociation into the single strands, for example, by one or more covalent, coordinative or ionic bonds. Oligoribonucleotides without such modifications however are preferred.

The Nucleotides in the RNA molecules can continue to use "non-standard" nucleotides, as well e.g. not natural occurring nucleotides or deoxyribonucleotides.

It has surprisingly proved that the Oligoribonukleotide after application of the compositions the skin inhibit the expression of the genes responsible for pigmentation the skin are responsible, and so the formation and distribution of the skin's own pigment melanin prevent side effects and In this way an effective treatment and prophylaxis of unwanted Enable pigmentation of the skin, without showing the disadvantages of the prior art. It is believed, that these Effect is due to that the oligoribonucleotides according to the invention be absorbed by the cells of the skin and intracellular degradation to induce the mRNAs of said genes by RNAi, giving details the mechanism of this reaction cascade are not yet known. The oligoribonucleotides are therefore particularly suitable for initiation the degradation of mRNA from participating in the pigmentation of the skin Structures and for inhibiting such structures in the skin and especially in skin cells.

The Compositions of the invention can additionally one or more oligoribonucleotides containing the expression the protein kinase inhibits PKR and thus a nonspecific inhibition counteract the translation.

Further the compositions of the invention are suitable for the treatment of UV rays, e.g. the ultraviolet part the sun's rays, skin damage caused. UVB rays (290 to 320 nm) cause, for example, erythema, sunburn or even more or less severe burns. UVA rays (320 nm to 400 nm) Irritations in photosensitive skin cause and lead to a damage the elastic and collagen fibers of the connective tissue what the Skin age prematurely. moreover they are the cause of numerous phototoxic and photoallergic Reactions. The oligoribonucleotides according to the invention are also suitable for the treatment of e.g. caused by UV rays structural damage and malfunctions in the epidermis and dermis of the skin, such as visible Vasodilation, like telangiectasia and cuperosis, skin laxity and training wrinkles, local hyper-, hypo- and false pigmentations, such. As age spots, and increased susceptibility to mechanical Stress, such as. Crackiness of the skin.

Further Application areas for the compositions of the invention are the treatment and prevention of aging and / or UV-induced Collagen degeneration and degradation of elastin and glycosaminoglycans; of degenerative phenomena of the skin, such as loss of elasticity and disappearance of the epidermal and dermal cell layers, the constituents the connective tissue, the pegs and capillaries) and / or the appendages; of environmental, e.g. by ultraviolet radiation, smoking, Smog, reactive oxygen species, free radicals and the like caused, negative changes the skin and the appendages; deficient, sensitive or hypoactive skin conditions or deficit, sensitive or hypoactive states of skin appendages; the reduction of skin thickness; of skin loosening and / or skin fatigue; of changes transepidermal water loss and normal moisture content of the skin; of change the energy metabolism of healthy skin; of deviations from the normal cell-cell communication in the skin, e.g. can express by wrinkling; of changes normal fibroblast and keratinocyte proliferation; of changes normal fibroblast and keratinocyte differentiation; from polymorphic photodermatosis, vitiligo; of wound healing disorders; of disorders normal collagen, hyaluronic acid, elastin and glycosaminoglycan homeostasis; the increased activation of proteolytic enzymes in the skin, such as B. of metalloproteinases.

Under Cosmetic skin care is first and foremost to understand that natural function the skin as a barrier against environmental influences (eg dirt, chemicals, Microorganisms) and against the loss of endogenous substances (eg Water, natural Fats, electrolytes) or restored. If this function is disturbed, can to strengthen it Absorption of toxic or allergenic substances or infestation of Microorganisms and as a result to toxic or allergic skin reactions come. The goal of skin care, it is further by the daily Washing to compensate for fat and water loss of the skin. This is important just when the natural regeneration capacity is not sufficient. Furthermore should skin care products against environmental influences, especially from the sun and wind, protect.

to Cosmetic application contain the compositions of the invention Therefore, preferably those components that are suitable for the purposes mentioned are. Such substances are known per se to the person skilled in the art. For example can one or more antisense oligoribonucleotides in usual cosmetic and dermatological preparations are incorporated, which in different forms may exist.

According to one particularly preferred embodiment are the compositions of the invention for cosmetic use as an emulsion, e.g. in form of a Cream, a lotion, a cosmetic milk. These contain beside said oligoribonucleotides further components such. Fats, oils, Waxes and / or other fat bodies, and water and one or more emulsifiers, as is customary for one such type of formulation can be used.

emulsions As a rule, a lipid or oil phase contains an aqueous phase and preferably also one or more emulsifiers. Especially preferred are compositions which also have one or more Hydrocolloids included.

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

The Lipid phase of the cosmetic according to the invention or dermatological emulsions can be advantageously chosen from the following group of substances: (1) mineral oils, mineral waxes; (2) oils, like Triglycerides of capric or caprylic acid, furthermore natural oils, e.g. Castor oil; (3) fats, waxes and other natural and synthetic fats, preferably esters of fatty acids with lower C number alcohols, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids of low C number or with fatty acids; (4) alkyl benzoates; (5) Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpoly-siloxanes and mixed forms thereof.

If Unless otherwise specified herein, lower C number is preferred 1 to 5, more preferably 1 to 3, and most preferably 3 carbon atoms understood.

The oil phase of Emulsions of the present invention are advantageously selected the group of esters from saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols of 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 of a chain length of 3 to 30 carbon atoms. Such ester oils can then chosen advantageous are from the group isopropyl myristate, isopropyl palmitate, isopropyl stearate, Isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, Isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyl dodecyl palmitate, Oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semisynthetic and natural Mixtures of such esters, e.g. Jojoba oil.

Further can the oil phase chosen favorably are from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ether, the group of saturated or unsaturated, branched or unbranched alcohols, as well as the fatty acid triglycerides, namely the triglycerol esters of saturated and / or unsaturated branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, especially 12-18 C-atoms. The fatty acid triglycerides can for example, advantageously chosen are selected from the group of synthetic, semi-synthetic and natural oils, e.g. Olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like more.

Also any mixtures of such oil and wax components are advantageous in the sense of the present Use invention. It may also be advantageous if Waxes, for example cetyl palmitate, as the sole lipid component the oil phase use.

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

Particularly advantageous are mixtures of C _12-15 -alkyl benzoate and 2-ethylhexyl isostearate, mixtures of C _12-15 -alkyl benzoate and isotridecyl isononanoate and mixtures of C _12-15 -alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.

From The hydrocarbons are paraffin oil, squalane and squalene advantageous to be used in the sense of the present invention.

Advantageously, the oil phase may further comprise a content of 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 silicone oils. Such silicones or silicone oils may be present as monomers, which are typically characterized by structural elements, as follows:

wobei die Siliciumatome mit gleichen oder unterschiedlichen Alkylresten und/oder Arylresten substituiert werden können, welche hier verallgemeinernd durch die Reste R₁–R₄ dargestellt sind (will sagen, daß die Anzahl der unterschiedlichen Reste nicht notwendig auf bis zu 4 beschränkt ist). m kann dabei Werte von 2–200.000 annehmen. Aryl steht hierin, wenn nicht anders angegeben, vorzugsweise für Phenyl.As linear silicones having several siloxy units which are advantageously used according to the invention, they are generally characterized by structural elements as follows:

wherein the silicon atoms can be substituted with identical or different alkyl radicals and / or aryl radicals, which are here generalized by the radicals R ₁ -R ₄ (to say that the number of different radicals is not necessarily limited to 4). m can assume values of 2 to 200,000. Aryl, unless otherwise stated, is herein preferably phenyl.

wobei die Siliciumatome mit gleichen oder unterschiedlichen Alkylresten und/oder Arylresten substituiert werden können, welche hier verallgemeinernd durch die Reste R₁–R₄ dargestellt sind (will sagen, daß die Anzahl der unterschiedlichen Reste nicht notwendig auf bis zu 4 beschränkt ist). n kann dabei Werte von 3/2 bis 20 annehmen. Gebrochene Werte für n berücksichtigen, daß ungeradzahlige Anzahlen von Siloxylgruppen im Cyclus vorhanden sein können.Cyclic silicones which are advantageously used in accordance with the invention are generally characterized by structural elements as follows

wherein the silicon atoms can be substituted with identical or different alkyl radicals and / or aryl radicals, which are here generalized by the radicals R ₁ -R ₄ (to say that the number of different radicals is not necessarily limited to 4). n can assume values of 3/2 to 20. Broken values for n take into account that odd numbers of siloxyl groups may be present in the cycle.

Advantageous For example, cyclomethicone (e.g., decamethylcyclopentasiloxane) is to be used in accordance with the present invention silicone oil used. But other silicone oils are beneficial in the sense of the present invention, for example undecamethylcyclotrisiloxane, Polydimethylsiloxane, poly (methylphenylsiloxane), cetyl dimethicone, Behenoxydimethicone.

Advantageous are also mixtures of cyclomethicone and isotridecyl isononanoate, and those of cyclomethicone and 2-ethylhexyl isostearate.

It but is also beneficial, silicone oils similar constitution as the to select compounds referred to above, the organic side chains derivatized, for example polyethoxylated and / or polypropoxylated are. These include For example, polysiloxane-polyalkyl-polyether copolymers such as Cetyl dimethicone copolyol, the (cetyl dimethicone copolyol (and) polyglyceryl-4-isostearate (and) hexyl laurate).

Especially also advantageous are mixtures of cyclomethicone and isotridecyl isononanoate, from cyclomethicone and 2-ethylhexyl isostearate.

The aqueous phase the preparations according to the invention contains optionally advantageous alcohols, diols or polyols lower 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, diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore lower alcohols C number, e.g. Ethanol, isopropanol, 1,2-propanediol, glycerin as well in particular one or more thickening agents, which or which chosen favorably can be from the group silicon dioxide, aluminum silicates.

Inventive as emulsions present preparations preferably contain one or more Emulsifiers. These emulsifiers can chosen favorably are from the group of nonionic, anionic, cationic or amphoteric emulsifiers.

Under The nonionic emulsifiers contain (1) partial fatty acid esters and fatty acid esters polyvalent Alcohols and their ethoxylated derivatives (eg glyceryl monostearates, Sorbitan stearates, glyceryl stearyl citrates, sucrose stearates); (2) ethoxylated fatty alcohols and fatty acids; (3) ethoxylated fatty amines, fatty acid amides, fatty acid; (4) Alkylphenol polyglycol ethers (e.g., Triton X).

Under the anionic emulsifiers contain soaps (eg sodium stearate); Fatty alcohol sulfates; Mono-, di- and Trialkylphosphosäureester and their ethoxylates.

Under The cationic emulsifiers contain quaternary ammonium compounds with a long chain aliphatic radical e.g. distearyldimonium Chlorides.

Under the amphoteric emulsifiers are alkylamininoalkanecarboxylic acids, betaines, Sulfobetaines, imidazoline derivatives.

Farther there are of course occurring emulsifiers, which include beeswax, wool wax, lecithin and Sterols belong.

O / W emulsifiers can be selected, for example, advantageously from the group of polyethoxylated or polypropoxylated or polyethoxylated and polypropoxylated products, for example the fatty alcohol ethoxylates, the ethoxylated wool wax alcohols, the polyethylene glycol ethers of the general formula RO - (- CH ₂ -CH ₂ -O- ) _n -R ', the fatty acid ethoxylates of the general formula R-COO - (- CH ₂ -CH ₂ -O-) _n -H, the etherified fatty acid ethoxylates of the general formula R-COO - (- CH ₂ -CH ₂ -O) _n -R ', the esterified fatty acid ethoxylates of the general formula R-COO - (- CH ₂ -CH ₂ -O-) _n -C (O) -R', the polyethylene glycol glycerin fatty acid esters, the ethoxylated sorbitan esters, the cholesterol ethoxylates, the ethoxylated triglycerides, the alkyl ether carboxylic acids of the general formula RO - (- CH ₂ -CH ₂ -O-) _n -CH ₂ -COOH, the polyoxyethylene sorbitol fatty acid esters, the alkyl ether sulfates of the general formula RO - (- CH ₂ -CH ₂ -O-) _n -SO ₃ -H, the fatty alcohol propoxylates of the general formula RO - (- CH ₂ - CH (CH ₃ ) -O-) nH, the polypropylene glycol ether of the general formula RO - (- CH ₂ -CH (CH ₃ ) -O-) _n -R ', the propoxylated wool wax alcohols, the etherified fatty acid propoxylates, R-COO- -CH ₂ -CH (CH ₃ ) -O-) _n -R ', the esterified fatty acid propoxylates of the general formula R-COO - (- CH ₂ -CH (CH ₃ ) -O-) _n -C (O) -R ', the fatty acid propoxylates of the general formula R-COO - (- CH ₂ -CH (CH ₃ ) -O-) _n -H, the polypropylene glycol glycerin fatty acid esters, the propoxylated sorbitan esters, the cholesterol propoxylates, the propoxylated triglycerides, the alkyl ether carboxylic acids of the general formula RO- (-CH ₂ -CH (CH ₃ ) O-) _n -CH ₂ -COOH, the alkyl ether sulfates or the acids underlying these sulfates of the general formula RO - (- CH ₂ -CH (CH ₃ ) -O-) _n - SO ₃ -H, the fatty alcohol ethoxylates / propoxylates of the general formula ROX _n -Y _m -H, the polypropylene glycol ethers of the general formula ROX _n -Y _m -R ', of the etherified fatty acid propoxylates of the general formula R-COO-X _n -Y _m - R ', the fatty acid ethoxylates / propoxylates of the general formula R-COO-X _n -Y _m -H.

The Variables n and m are in each case independent of each other for a whole Number from 1 to 40, preferably 5 to 30.

Particularly according to the invention The polyethoxylated or polypropoxylated used are advantageous or polyethoxylated and polypropoxylated O / W emulsifiers selected from the group of substances with HLB values of 11-18, very particularly advantageous with HLB values of 14.5-15.5, provided that the O / W emulsifiers saturated Radicals R and R 'have. Do the O / W emulsifiers have unsaturated Radicals R and / or R ', or are Isoalkylderivate, so the preferred HLB value such emulsifiers are also lower or higher.

It is advantageous to choose the fatty alcohol ethoxylates from the group of ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). Particularly preferred are:
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 col (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 (oleth-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) cetyl stearyl ether ( Ceteareth-17), polyethylene glycol (18) cetyl stearyl ether (ceteareth-18), polyethylene glycol (19) cetyl stearyl ether (ceteareth-19), polyethylene glycol (20) cetyl stearyl 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, polyethylene glycol (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.

When ethoxylated alkyl ether carboxylic acid or its salt may advantageously be the sodium laureth-11-carboxylate be used.

When Alkyl ether sulfate can be advantageously used sodium laureth 1-4 sulfate become.

When Ethoxylated cholesterol derivative may advantageously be polyethylene glycol (30) cholesteryl ether be used. Also, polyethylene glycol (25) sojasterol has become proven.

When ethoxylated triglycerides can Advantageously, the Polyethylene Glycol (60) Evening Primrose Glycerides is used become (Evening Primrose = evening primrose).

Farther is advantageous, the Polyethylenglycolglycerinfettsäureester 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, polyethylene glycol (20) glyceryl oleate, Polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate / cocoate to choose.

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

When advantageous W / O emulsifiers can be used: fatty alcohols having 8 to 30 carbon atoms, Monoglycerol ester saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, especially 12-18 C atoms, diglycerol esters saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, especially 12-18 C atoms, monoglycerol ether saturated and / or unsaturated, branched and / or unbranched alcohols of a chain length of 8 to 24, especially 12-18 C atoms, diglycerol ether saturated and / or unsaturated, branched and / or unbranched alcohols of a chain length of 8 to 24, especially 12-18 C atoms, propylene glycol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, especially 12-18 C atoms and saturated sorbitan esters and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, especially 12-18 C-atoms.

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

Inventive as emulsions In addition, present preparations preferably also contain one or more hydrocolloids. These hydrocolloids can be beneficial chosen are from the group of gums, polysaccharides, cellulose derivatives, Phyllosilicates, polyacrylates and / or other polymers.

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

To counting the gums you plant or tree juices, which harden in the air and resins or extracts from aquatic plants. From this group can be selected advantageously in the context of the present invention for example gum arabic, locust bean gum, tragacanth, karaya, Guar gum, pectin, gellan gum, carrageenan, agar, algine, chondrus, Xanthan gum.

Also advantageous is the use of derivatized gums such as hydroxypropyl guar ( ^Jaguar® HP 8).

Under the polysaccharides and derivatives are e.g. Hyaluronic acid, chitin and chitosan, chondroitin sulfates, starch and starch derivatives.

Under the cellulose derivatives are e.g. Methylcellulose, carboxymethylcellulose, Hydroxyethylcellulose, hydroxypropylmethylcellulose.

The phyllosilicates 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 modified form, such as stearylalkonium hectorites.

Farther can also advantageous silica gel be used.

Under the polyacrylates are e.g. Carbopol types of the company Goodrich (Carbopol 980, 981, 1382, 5984, 2984, EDT 2001 or Pemulen TR2).

Under the polymers are e.g. Polyacrylamide (Seppigel 305), Polyvinyl alcohols, PVP, PVP / VA copolymers, polyglycols.

According to one another preferred embodiment are used in the invention Oligoribonucleotides in aqueous systems or surfactant preparations for cleaning the skin and hair inserted.

The cosmetic according to the invention Preparations preferably contain in addition to the components mentioned also adjuvants, as they usually do used in such preparations, e.g. Preservatives, Bactericides, deodorants, antiperspirants, Insect repellents, vitamins, antifoaming agents, dyes, Pigments with coloring Effect, thickener, softening substances, moisturizing and / or moisturizing substances (moisturizers), or other common ingredients a cosmetic formulation such as polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives, antioxidants and in particular UV absorbers.

Moisturizers are substances or mixtures of substances which give cosmetic or dermatological preparations the property of reducing the moisture release of the horny layer (also called transepidermal water loss (TEWL) after application or spreading on the skin surface) and / or hydrating the horny layer positively to influence. Advantageous moisturizers for the purposes of the present invention are, for example, glycerol, lactic acid, pyrrolidonecarboxylic 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-gellable polysaccharides. For example, hyaluronic acid and / or a fucose-rich polysaccharide which is described in the Chemical Abs filed under the registration number 178463-23-5 and z. B. under the name Fucogel⎕1000 by the company SOLABIA SA is available.

glycerin is preferred for use as a particularly preferred moisturizer in an amount of 0.05-30 % By weight, more preferably 1-10% are used.

The cosmetic compositions can Advantageously, one or more of the following natural Active substances or a derivative thereof contain: alpha-lipoic acid, phytoene, D-biotin, coenzyme Q10, alpha glucosylrutin, carnitine, carnosine, natural and / or synthetic isoflavonoids, creatine, hops and hops malt extract, Taurine. It turned out that active substances have a positive influence the aging skin, the formation of wrinkles or even existing ones Reduce wrinkles, such as biochinones and especially ubiquinone Q10, Soy, creatinine, creatine, liponamide, or the restructuring of the Promote connective tissue, like isoflavone, very well in the formulations of the invention can be used. It also showed that the formulations in a special way for combination with active ingredients to support the skin functions dry skin, especially age-dry skin, such as serinol and Osmolytes, e.g. Taurine, suitable. In a similar way proved the incorporation of active substances for the relief or positive influence of irritative skin conditions, be it with sensitive skin in general or by noxious irritated skin (UV light, chemicals), as beneficial. Here are Such as sericosides, various extracts of licorice, Licochalcone, in particular the licochalcone A, silymarin, silyphos, Dexpanthenol, inhibitors of prostaglandin metabolism (in particular cyclooxygenase) and leukotriene metabolism (in particular the 5-lipoxygenase, but also the 5-lipoxygenase inhibitor protein, FLAP). The incorporation of modulators of pigmentation was also proved as advantageous. Here are agents to name the pigmentation reduce the skin and so to a cosmetically desired Brighten the skin and / or reduce the occurrence of age spots and / or existing ones Age spots lighten (tyrosine sulfate, dioic acid (8-hexadecene-1,16-dicarboxylic acid), lipoic acid and Liponamide, various extracts of licorice, kojic acid, hydroquinone, Arbutin, fruit acids, especially alpha hydroxy acids (AHAs), Bearberry (Uvae ursi), ursolic acid, ascorbic acid, green tea extracts).

According to one particularly preferred embodiment contain the compositions of the invention one or more UV absorbers. Preferred UV absorbers are those which absorb in the range of UVB and / or UVA rays.

To the Protection against UVB radiation, numerous compounds are known which are derivatives of 3-Benzylidencamphers, 4-aminobenzoic acid, the cinnamic acid, salicylic acid, benzophenone and 2-phenylbenzimidazole. Prefers are filters with an absorption maximum in the range of 308 nm, because here is the maximum of the erythema efficiency of sunlight.

Advantageous UV-A filter substances for the purposes of the present invention are dibenzoylmethane derivatives, in particular 4- (tert-butyl) -4'-methoxydibenzoylmethane (CAS-Nr. 70356-09-1), marketed by Givaudan under the trade name Parsol ^® 1789 and is sold by Merck under the trade name Eusolex ^® 9020th

The Preparations according to the invention advantageously contain substances that UV radiation in the UV-A and / or UV-B range absorb, wherein the total amount of the filter substances z. 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 Preparations available to put the hair or the skin in front of the entire area protect the ultraviolet radiation. You can also as a sunscreen for Hair or the skin serve.

und ihre Salze, besonders die entsprechenden Natrium-, Kalium- oder Triethanolammonium-Salze, insbesondere das Phenylen-1,4-bis-(2-benzimidazyl)-3,3'-5,5'-tetrasulfonsäure-bis-natriumsalz

mit der INCI-Bezeichnung Bisimidazylate, welches beispielsweise unter der Handelsbezeichnung Neo Heliopan AP bei Haarmann & Reimer erhältlich ist.Further advantageous UV-A filter substances are the phenylene-1,4-bis (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid

and their salts, especially the corresponding sodium, potassium or triethanolammonium salts, especially the phenylene-1,4-bis (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid bis-sodium salt

with the INCI name bisimidazylate, which is available, for example, under the trade name Neo Heliopan AP from Haarmann & Reimer.

Also advantageous are the 1,4-di (2-oxo-10-sulfo-3-bomylidenemethyl) benzene and its salts (especially the corresponding 10-sulfato compounds, in particular the corresponding sodium, potassium or triethanolammonium salt) which is also referred to as benzene-1,4-di (2-oxo-3-bomylidenemethyl-10-sulfonic acid) and is characterized by the following structure:

advantageous UV filter substances in the context of the present invention are further so-called broadband filters, i. Filter substances containing both UV-A as well as absorb UV-B radiation.

wobei R¹, R² und R³ unabhängig voneinander gewählt werden aus der Gruppe der verzweigten und unverzweigten Alkylgruppen mit 1 bis 10 Kohlenstoffatomen bzw. ein einzelnes Wasserstoffatom darstellen. Insbesondere bevorzugt sind das 2,4-Bis-{[4-(2-Ethylhexyloxy)-2-hydroxy]-phenyl}-6-(4-meihoxyphenyl)-1,3,5-triazin (INCI: Aniso Triazin), welches unter der Handelsbezeichnung Tinosorb^® S bei der CIBA-Chemikalien GmbH erhältlich ist, und das 4,4',4''-(1,3,5-Triazin-2,4,6-triyltriimino)-tris-benzoesäure-tris(2-ethylhexylester), synonym: 2,4,6-Tris-(anilino-(p-carbo-2'-ethyl-1'-hexyloxy)]-1,3,5-triazin (INCI: Octyl Triazone), welches von der BASF Aktiengesellschaft unter der Warenbezeichnung UVINUL^® T 150 vertrieben wird.Advantageous broadband filters or UV-B filter substances are, for example, bis-resorcinyl triazine derivatives having the following structure:

wherein R ¹ , R ² and R ^{3 are} independently selected from the group of branched and unbranched alkyl groups having 1 to 10 carbon atoms or represent a single hydrogen atom. Particularly preferred are 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxy] -phenyl} -6- (4-meihoxyphenyl) -1,3,5-triazine (INCI: aniso triazine), which is available under the trade name Tinosorb ^® S from CIBA-Chemikalien GmbH, and the 4,4 ', 4''- (1,3,5-triazine-2,4,6-triyltriimino) tris-benzoic acid tris (2-ethylhexyl ester), synonym: 2,4,6-tris- (anilino- (p-carbo-2'-ethyl-1'-hexyloxy)] - 1,3,5-triazine (INCI: Octyl Triazone), which is marketed by BASF Aktiengesellschaft under the trade name Uvinul ^® T 150th

aufweisen, sind vorteilhafte UV-Filtersubstanzen im Sinne der vorliegenden Erfindung, beispielsweise die in der Europäischen Offenlegungsschrift EP 570 838 A1 beschriebenen s-Triazinderivate, deren chemische Struktur durch die generische Formel

wiedergegeben wird, wobei
R einen verzweigten oder unverzweigten C₁-C₁₈-Alkylrest, einen C₅-C₁₂-Cycloalkylrest, gegebenenfalls substituiert mit einer oder mehreren C₁-C₄-Alkylgruppen, darstellt,
X ein Sauerstoffatom oder eine NH-Gruppe darstellt,
R₁ einen verzweigten oder unverzweigten C₁-C₁₈-Alkylrest, einen C₅-C₁₂-Cycloalkylrest, gegebenenfalls substituiert mit einer oder mehreren C₁-C₄-Alkylgruppen, oder ein Wasserstoffatom, ein Alkalimetallatom, eine Ammoniumgruppe oder eine Gruppe der Formel

bedeutet, in welcher
A einen verzweigten oder unverzweigten C₁-C₁₈-Alkylrest, einen C₅-C₁₂-Cycloalkyl- oder Arylrest darstellt, gegebenenfalls substituiert mit einer oder mehreren C₁-C₄-Alkylgruppen,
R₃ ein Wasserstoffatom oder eine Methylgruppe darstellt,
n eine Zahl von 1 bis 10 darstellt,
R₂ einen verzweigten oder unverzweigten C₁-C₁₈-Alkylrest, einen C₅-C₁₂-Cycloalkylrest, gegebenenfalls substituiert mit einer oder mehreren C₁-C₄-Alkylgruppen, darstellt, wenn X die NH-Gruppe darstellt, und
einen verzweigten oder unverzweigten C₁-C₁₈-Alkylrest, einen C₅-C₁₂-Cycloalkylrest, gegebenenfalls substituiert mit einer oder mehreren C₁-C₄-Alkylgruppen, oder ein Wasserstoffatom, ein Alkalimetallatom, eine Ammoniumgruppe oder eine Gruppe der Formel

bedeutet, in welcher
A einen verzweigten oder unverzweigten C₁-C₁₈-Alkylrest, einen C₅-C₁₂-Cycloalkyl- oder Arylrest darstellt, gegebenenfalls substituiert mit einer oder mehreren C₁-C₄-Alkylgruppen,
R₃ ein Wasserstoffatom oder eine Methylgruppe darstellt,
n eine Zahl von 1 bis 10 darstellt,
wenn X ein Sauerstoffatom darstellt.Other UV filter substances, which are the structural motif

have advantageous UV filter substances in the sense of the present invention, for example, those in the European published patent application EP 570 838 A1 described s-triazine derivatives, their chemical structure by the generic formula

is reproduced, wherein
R is a branched or unbranched C ₁ -C ₁₈ -alkyl radical, a C ₅ -C ₁₂ -cycloalkyl radical, optionally substituted by one or more C ₁ -C ₄ -alkyl groups,
X represents an oxygen atom or an NH group,
R _{1 is} a branched or unbranched C ₁ -C ₁₈ alkyl radical, a C ₅ -C ₁₂ cycloalkyl radical optionally substituted with one or more C ₁ -C ₄ alkyl groups, or a hydrogen atom, an alkali metal atom, an ammonium group or a group of formula

means in which
A is a branched or unbranched C ₁ -C ₁₈ -alkyl radical, a C ₅ -C ₁₂ -cycloalkyl or aryl radical, optionally substituted by one or more C ₁ -C ₄ -alkyl groups,
R _{3 represents} a hydrogen atom or a methyl group,
n represents a number from 1 to 10,
R _{2 is} a branched or unbranched C ₁ -C ₁₈ alkyl radical, a C ₅ -C ₁₂ cycloalkyl radical optionally substituted with one or more C ₁ -C ₄ alkyl groups, when X represents the NH group, and
a branched or unbranched C ₁ -C ₁₈ alkyl radical, a C ₅ -C ₁₂ cycloalkyl radical optionally substituted with one or more C ₁ -C ₄ alkyl groups, or a hydrogen atom, an alkali metal atom, an ammonium group or a group of the formula

means in which
A is a branched or unbranched C ₁ -C ₁₈ -alkyl radical, a C ₅ -C ₁₂ -cycloalkyl or aryl radical, optionally substituted by one or more C ₁ -C ₄ -alkyl groups,
R _{3 represents} a hydrogen atom or a methyl group,
n represents a number from 1 to 10,
when X represents an oxygen atom.

wiedergegeben wird, welches im Folgenden auch als Dioctylbutylamidotriazon (INCI: Dioctylbutamidotriazone) bezeichnet wird und unter der Handelsbezeichnung UVASORB HEB bei Sigma 3V erhältlich ist.A particularly advantageous UV filter substance in the context of the present invention is also an unsymmetrically substituted s-triazine whose chemical structure is represented by the formula

which is also referred to below as Dioctylbutylamidotriazon (INCI: Dioctylbutamidotriazone) and is available under the trade name UVASORB HEB in Sigma 3V.

wiedergegeben wird, wobei R₁, R₂ und A₁ verschiedenste organische Reste repräsentieren.Also in the European patent application EP 775 698 are advantageously used bis-Resorcinyltriazinderivate described their chemical structure by the generic formula

is reproduced, wherein R ₁ , R ₂ and A _{1 represent a} variety of organic radicals.

Also advantageous for the purposes of the present invention are 2,4-bis - {[4- (3-sulfonato) -2-hydroxy-propyloxy) -2-hydroxy] -phenyl} -6- (4-methoxyphenyl) -1, 3,5-triazine sodium salt containing 2,4-bis - {[4- (3- (2-propyloxy) -2-hydroxy-propyloxy) -2-hydroxy] -phenyl} -6- (4-methoxyphenyl) - 1,3,5-triazine, the 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] -phenyl} -6- [4- (2-methoxyethylcarboxyl) -phenylamino] 1,2,3,5-triazine which is 2,4-bis - {[4- (3- (2-propyloxy) -2-hydroxypropyloxy) -2-hydroxy] -phenyl} -6- [4- (2- ethyl-carboxyl) -phenylami no] -1,3,5-triazine, 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] -phenyl} -6- (1-methylpyrrol-2-yl ) -1,3,5-triazine which is 2,4-bis - {[4-tris (trimethylsiloxy-silylpropyloxy) -2-hydroxy] -phenyl} -6- (4-methoxyphenyl) -1,3,5- triazine which is 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.

gekennzeichnet ist und unter der Handelsbezeichnung Tinosorb^® M bei der CIBA-Chemikalien GmbH erhältlich ist.An advantageous broadband filter for the purposes of the present invention is the 2,2'-methylenebis- (6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) -phenol) [INCI: bisoctyltriazole ], which by the chemical structural formula

is characterized and is available under the trade name Tinosorb ^® M from CIBA-Chemikalien GmbH.

gekennzeichnet ist.Advantageous broadband filter according to the present invention is further the 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 represented by the chemical structural formula

is marked.

The UV-B filters can be oil-soluble or water soluble be. Advantageous oil-soluble UV-B filter substances are z. B.: 3-benzylidene camphor derivatives, preferably 3- (4-methylbenzylidene) camphor, 3-benzylidenecamphor; 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; Ester of benzalmalonic, preferably di (2-ethylhexyl) 4-methoxybenzalmalonate; ester cinnamic acid, preferably 4-methoxycinnamate (2-ethylhexyl) ester, 4-methoxycinnamate; Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone as well as polymers bound to UV filters.

advantageous water-soluble UV-B filter substances are z. B. salts of 2-phenylbenzimidazole-5-sulfonic acid, as their sodium, potassium or their triethanolammonium salt, as well as the sulfonic acid even; Sulphonic acid derivatives of the 3-benzylidene camphor, such as B. 4- (2-oxo-3-bomylidenemethyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bomylidenemethyl) sulfonic acid and their salts.

A weiterere according to the invention can be used advantageously light protection filter substance is ethylhexyl-2-cyano-3,3-diphenylacrylate (octocrylene), which is under the name Uvinul ^® N 539 available from BASF and is characterized by the following structure:

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

Also particularly advantageous according to the invention are benzoxazole derivatives such as, in particular, 2,4-bis- [5-1 (dimethylpropyl) benzoxazol-2-yl- (4-phenyl) -imino] -6- (2-ethylhexyl) -imino-1 , 3,5-triazine with the CAS No. 288254-16-0, which is available, for example, under the trade name Uvasorb ^® K2A, and hydroxybenzophenones, in particular the 2- (4'-diethylamino-2'-hydroxybenzoyl) -benzoesäurehexylester or Aminobenzophenone, which is available under the Uvinul A Plus.

Further may it be advantageous, according to the invention further UV-A and / or UV-B filters in to incorporate cosmetic or dermatological preparations, for example certain salicylic acid derivatives such as 4-isopropylbenzylsalicylate, 2-ethylhexylsalicylate (= octylsalicylate), Homomenthyl.

The List of said UV filters, for the purposes of the present invention can be used Of course not limiting.

Farther can the compositions of the invention Antioxidants for the protection of the cosmetic preparation itself or to protect the ingredients of the cosmetic preparations from harmful Contain oxidation processes.

Advantageously, the antioxidants are selected 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 (eg anserine), carotenoids, carotenes (eg α-carotene, β-carotene, lycopene) and their derivatives, retinol, aurothioglucose, propylthiouracil and other thiols (eg 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) and sulfoximine compounds (eg Buthioninsulfoximine, Homocysteinsulfoximin, Buthioninsulfone, penta-, hexa-, Heptathioninsulfoximin) in very low tolerated dosages (eg pmol to microns ol / kg), furthermore (metal) chelators (eg α-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (eg 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 (eg γ-linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, alaninediacetic acid, flavonoids, polyphenols, catechins, vitamin C and derivatives (eg ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (Eg, vitamin E acetate), and Koniferylbenzoat of benzoin, rutinic acid and its derivatives, ferulic acid and its derivatives, butylhydroxytoluene, Butylhydroxyanisol, Nordihydroguajakharzsäure, Nordihydroguajaretsäure, trihydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ) selenium and its derivatives (eg selenium methionine), stilbenes and their derivatives (eg stilbene oxide, Tran s-stilbene oxide) and the inventively suitable derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active substances.

The Amount of antioxidants (one or more compounds) in the Preparations is preferably from 0.001 to 30% by weight, particularly preferably from 0.05 to 20% by weight, especially 1-10 Wt .-%, based on the total weight of the preparation.

Cosmetic and therapeutic preparations according to the invention advantageously also contain inorganic pigments based on metal oxides and / or other sparingly soluble or insoluble metal compounds, in particular the oxides of titanium (TiO ₂ ), zinc (ZnO), iron (eg Fe ₂ O ₃ ), zirconium niums (ZrO ₂ ), silicon (SiO ₂ ), manganese (eg MnO), aluminum (Al ₂ O ₃ ), cerium (eg Ce ₂ O ₃ ), mixed oxides of the corresponding metals and mixtures of such oxides. Particular preference is given to pigments based on TiO ₂ .

It is particularly advantageous in the context of the present invention, although not mandatory if the inorganic pigments are in hydrophobic form that is, they superficial are treated water-repellent. This surface treatment can consist of that the Pigments according to known methods with a thin hydrophobic Layer be provided.

One such method is, for example, that the hydrophobic surface layer according to a reaction according to nTiO ₂ + m (RO) ₃ Si-R '→ nTiO ₂ (surface) n and m are stoichiometric parameters to be used at will, R and R 'are the desired organic radicals. For example, in analogy to DE-OS 33 14 742 illustrated hydrophobized pigments are advantageous.

Advantageous TiO ₂ pigments are available, for example, under the trade names MT 100 T from TAYCA, furthermore M 160 from Kemira and T 805 from Degussa.

Preparations according to the invention can, especially when crystalline or microcrystalline solids, for example inorganic micropigments incorporated into the preparations according to the invention are also anionic, nonionic and / or amphoteric Containing surfactants. Surfactants are amphiphilic substances that are organic, Dissolve nonpolar substances in water can.

The hydrophilic portions of a surfactant molecule are usually polar functional groups, for example -COO ^- , -OSO ₃ ^2- , -SO ₃ ^- , while the hydrophobic parts are usually nonpolar hydrocarbon radicals. Surfactants are generally classified according to the nature and charge of the hydrophilic part of the molecule. Here, four groups can be distinguished, namely anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants.

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 medium. Cationic surfactants are almost exclusively characterized 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 behave accordingly in aqueous solution depending on the pH as anionic or cationic surfactants. 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 is intended to illustrate: pH = 2 RNH ₂ ⁺ CH ₂ CH ₂ COOH X ^- (X ^- = any anion, eg Cl ^- ) pH = 7 RNH ₂ ⁺ CH ₂ CH ₂ COO ^- pH = 12 RNHCH ₂ CH ₂ COO ^- B ⁺ (B ⁺ = any cation, eg Na ⁺ )

Typical for non-ionic Surfactants are polyether chains. Nonionic surfactants form in aqueous medium no ions.

Advantageously used anionic surfactants are:
Acyl amino acids (and their salts), such as (1) acyl glutamates, for example, sodium acyl glutamate, di-TEA palmitoyl aspartate, and sodium caprylic / capric glutamate; (2) acyl peptides, for example, palmitoyl-hydrolyzed milk protein, sodium cocoyl-hydrolyzed soy protein and sodium / potassium cocoyl-hydrolyzed collagen; (3) sarcosinates, for example myristoyl sarcosine, TEA lauroyl sarcosinate, sodium lauroyl sarcosinate and sodium cocoyl sarcosinate; (4) taurates, for example, 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 alkoxide and zinc kundecylenat; 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, eg, sodium / ammonium cocoyl isethionate; (2) alkylarylsulfonates; (3) alkyl sulfonates, for example, 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 undecylenamido 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 _12-14 pareth sulfate; (2) Alkyl sulfates, for example, sodium, ammonium and TEA lauryl sulfate.

Advantageous cationic surfactants to be used are alkylamines, alkylimidazoles, Ethoxylated amines and quaternaries Surfactants and esterquats.

Quaternary surfactants contain at least one N-atom containing 4 alkyl or aryl groups covalently linked. This leads to, independently from pH, to a positive charge. Advantageous are alkyl betaine, Alkylamidopropyl betaine and alkyl amidopropyl hydroxysulfine. The used according to the invention cationic surfactants can furthermore preferably chosen are selected from the group of quaternary ammonium compounds, in particular Benzyltrialkylammoniumchloride or bromides, such as Benzyldimethylstearylammonium chloride, further alkyltrialkylammonium salts, for example, cetyltrimethylammonium chloride or bromide, alkyldimethylhydroxyethylammonium chlorides or bromides, dialkyldimethylammonium chlorides or bromides, alkylamidoethyltrimethylammonium ether sulphates, Alkylpyridinium salts, for example lauryl or cetylpyrimidinium chloride, Imidazoline derivatives and compounds with cationic character such as Amine oxides, for example Alkyldimethylaminoxide or Alkylaminoethyldimethylaminoxide. Cetyltrimethylammonium salts are particularly advantageous to use.

Advantageous amphoteric surfactants to be used are (1) acyl / dialkylethylenediamine, for example, sodium acylamphoacetate, disodium acylamphodipropionate, Disodium alkyl amphodiacetate, sodium acyl amphohydroxypropyl sulfonate, Disodium acyl amphodiacetate and sodium acyl amphopropionate; (2) N-alkyl amino acids, for example Aminopropylalkylglutamide, alkylaminopropionic acid, sodium alkylimidodipropionate and lauroamphocarboxyglycinate.

Advantageous nonionic surfactants to be used are (1) alcohols; (2) alkanolamides, like Cocamide MEA / DEA / MIPA; (3) amine oxides such as cocoamidopropylamine oxide; (4) esters obtained by esterification of carboxylic acids with ethylene oxide, glycerol, Sorbitan or other alcohols arise; (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 polyglycosides such as lauryl glucoside, Decyl glycoside and cocoglycoside; (6) sucrose esters, ethers; (7) polyglycerol ester, Diglycerol ester, monoglycerol ester; (8) methyl glucose esters, esters of hydroxy acids.

Advantageous is also the use of a combination of anionic and / or amphoteric surfactants with one or more non-ionic surfactants.

The surfactants Substance can be in a concentration between 1 and 95 wt .-% in the preparations according to the invention present, based on the total weight of the preparations.

preparations for medical use differ in their composition not from the cosmetic products and can also do the above Contain substances. They differ from these in the first place in that they have to go through a special authorization procedure.

in the Following, the invention will be explained in more detail with reference to embodiments. In In the examples, all numbers are by weight, provided that nothing else is stated.

It is possible in all cases in individual cases that the aforementioned concentration data are easily exceeded or fallen short of and still preparations of the invention are obtained. This comes in the face of the wide variety of suitable components of such preparations for the expert not unexpected, so that he knows that in such overrun or underrun the soil of the present invention is not left.

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

Examples

Example 1: Preparation of PIT emulsions

By Mixing of the components listed in the table were phase inversion temperature emulsions (PIT emulsions) of the composition also indicated. As an oligoribonucleotide, dsRNA was used by hybridization of sequences SEQ ID NOs. 37 and 38 was obtained. The dsRNA points 3'-constantly two supernumeraries dT residues on. The dsRNA is for the cDNA of tyrosinase specific and inhibits the expression of the gene of this enzyme by RNA interference. It is therefore referred to as anti-tyrosian dsRNA. The rest in Abbreviations used in the examples are to be understood accordingly.

Table 1: PIT emulsions

On Similarly, a PIT emulsion was prepared using dsRNA prepared by hybridizing the sequences SEQ NOs 44 and 45 was obtained. The amounts levied to anti-tyrosinase dsRNA depends on the total amount of dsRNA, which is divided equally the said respective sequences (SEQ IDs).

Example 2: Preparation of creams based on oil-in-water emulsions

By Blending of the components listed in the table were creams the composition also indicated.

Table 2: O / W creams

Table 2: O / W creams (continued)

On Similarly, a cream was prepared using anti-tyrosinase dsRNA prepared by hybridizing the sequences SEQ NOs 43 and 45 was obtained. The amounts delivered to anti-tyrosinase dsRNA, anti-PAR-2 dsRNA, anti-MITF dsRNA and anti-P protein dsRNA each relate to the total amount of dsRNA, which is divided equally from those mentioned, respective sequences (SEQ IDs) to the individual target genes.

Example 3: Production of water-in-oil emulsions

By Mixing of the components listed in the table were also water-in-oil emulsions prepared composition. As oligoribonucleotide dsRNA was used by hybridizing the sense RNA and Antisense RNA strand to SEQ ID NO 40 was obtained. SEQ ID NO Figure 40 is a section of the tyrosinase cDNA. The two strands of the dsRNAs were 3'-steady respectively two 2'-deoxythymidine residues on.

Table 3: W / O emulsions

Table 3: W / O Emulsions (continued)

Example 4: Preparation of hydrodispersions

By mixing the components indicated in the table, hydrodispersions of the composition also indicated were prepared. As oligoribonucleotide 5, dsRNA obtained by hybridizing the sense RNA and antisense RNA strand to cDNA of PAR-2 was used. SEQ ID NOs 115 and 117 is a portion of the cDNA of PAR-2. The two strands of the dsRNA had 3'-constantly two 2'-Desoxythymidinreste. The amounts delivered to anti-PAR-2 dsRNA are based on the total Amount of dsRNA, which is composed in equal parts of the said, respective 0 sequences (SEQ IDs).

Table 4: Hydrodispersions

Example 5: Preparation a gel cream

By Mixing the components listed in the table became a gel cream the composition also indicated. The pH the gel cream became 5 afterwards set to 6.0.

Table 5: Gel cream

On analogously, a gel cream was prepared using dsRNA, obtained by hybridizing the sequences SEQ NOs 38 and 39 has been. The amounts delivered to anti-tyrosinase dsRNA relate to the total amount of dsRNA, which is divided equally from the composed, respective sequences (SEQ IDs).

Example 6: Preparation a cream based on a water-in-oil emulsion

By Mixing the components listed in the table became a cream the likewise indicated composition based on a water-in-oil dispersion produced.

Table 6: W / O cream

On analogously, an emulsion was prepared using dsRNA, obtained by hybridizing the sequences SEQ NOs 70, 71 and 85 has been. The amounts delivered to anti-MITF dsRNA refer to the Total amount of dsRNA, equal in number to those mentioned, respective sequences (SEQ IDs) composed.

Example 7: Preparation a cream based on a water-in-oil-in-water emulsion

By Mixing the components listed in the table became a cream the composition also indicated based on a water-in-oil-in-water dispersion prepared. As an oligoribonucleotide, dsRNA was used by hybridization of the sense RNA and antisense RNA strand to SEQ ID NO 38 has been. The two strands the dsRNAs were 3'-steady respectively two 2'-deoxythymidine residues on.

Table 7: W / O / W cream

pictures:

The 1 shows the single-stranded cDNA of tyrosinase Related Protein-1 (TRP-1), in which all fragments of the form AA-N ₁₉ -TT and AA-N ₁₉ -TC are optically highlighted. The representation is in two blocks, each containing the identical cDNA sequence region. In the first block the fragments of the form AA-N ₁₉ -TT are highlighted, in the second block those of the form AA-N ₁₉ -TC.

In 2 these fragments (targeted region) are shown by way of example together with the corresponding homologous (senseRNA) and complementary (antisenseRNA) RNA single strands. Shown are single-stranded RNAs which are 3'-modified by two deoxythymidine residues (dt). Hybridization of two complementary single-stranded RNAs yields dsRNA with protruding 3 'ends, each formed by two 2'-deoxythymidine residues. The representation shown here is exemplary for SEQ ID NO 1 and SEQ ID NO 22, wherein the respective sense RNA is shown with 1a or 22a and the respective antisense RNA with 1b and 22b. From 1a and 1b or 22a and 22b, the respective dsRNA from SEQ ID NO 1 or SEQ ID NO 22 is formed. The formation of the dsRNA of the remaining sequences is analogous.

The gene of tyrosinase-related protein-1 (TRP-1) belongs to the preferred target genes for the oligoribonucleotides according to the invention. Oligoribonucleotides derived from the in 1 sequence shown deduced double-stranded sequence, portions thereof and in particular to the double-stranded sequences of the in 1 are derived homologous, are accordingly particularly preferred according to the invention. Under the of the in 1 sequence shown deduced double-stranded sequence is understood to be the sequence consisting of the in 1 shown sequence and the complementary strand is formed. The other information should be understood accordingly.

In 3 is the single-stranded cDNA of tyrosinase to see. Tyrosinase is one of the most preferred genes. Again, a preferred sequence region, ie, a sequence region of 19 nucleotides long flanked by AA and TT or TC, is highlighted; the representation is analogous to 1 , Oligoribonucleotides derived from the in 3 shown sequence derived double stranded sequence, portions thereof and in particular to the double-stranded sequence of the in 3 are derived homologous, are also preferred according to the invention.

In 4 is the single-stranded cDNA of tyrosinase-like protein 2 (TRP2) to see. Again, a preferred sequence region, ie, a sequence region of 19 nucleotides long flanked by AA and TT or TC, is highlighted; the representation is analogous to 1 , Oligoribonucleotides derived from the in 4 sequence shown deduced double-stranded sequence, portions thereof and in particular to the double-stranded sequence of the in 4 are derived homologous, are also preferred according to the invention. The formation of the respective dsRNA takes place analogously to 2 ,

In 5 is the single-stranded cDNA of MITF seen. Again, a preferred sequence region, ie, a sequence region of 19 nucleotides long flanked by AA and TT or TC, is highlighted; the representation is analogous to 1 , Oligoribonucleotides derived from the in 5 sequence shown deduced double-stranded sequence, portions thereof and in particular to the double-stranded sequence of the in 5 are derived homologous, are also preferred according to the invention. The formation of the respective dsRNA takes place analogously to 2 ,

In 6 is the single-stranded cDNA of the P protein can be seen. Again, a preferred sequence region, ie, a sequence region of 19 nucleotides long flanked by AA and TT or TC, is highlighted; the representation is analogous to 1 , Oligoribonucleotides derived from the in 6 sequence shown deduced double-stranded sequence, portions thereof and in particular to the double-stranded sequence of the in 6 are derived homologous, are also preferred according to the invention. The formation of the respective dsRNA takes place analogously to 2 ,

In 7 the single-stranded cDNA of PAR-2 can be seen. Again, a preferred sequence region, ie, a sequence region of 19 nucleotides long flanked by AA and TT or TC, is highlighted; the representation is analogous to 1 , Oligoribonucleotides derived from the in 7 sequence shown deduced double-stranded sequence, portions thereof and in particular to the double-stranded sequence of the in 7 are derived homologous, are also preferred according to the invention. The formation of the respective dsRNA takes place analogously to 2 ,

SEQUENCE LISTING

Claims (29)

double Oligoribonucleotide or a physiologically acceptable salt thereof, which in is capable of breaking down mRNA from one or more of the Pigmentation of the skin and / or hair involved structures to induce. Oligoribonucleotide according to claim 1, characterized in that that the structures involved in the pigmentation of the skin and / or hair on (I) the actual melanin synthesis (melanosome structures) and / or on the (II) expression of these melanosomal structures and / or on the (III) transfer of melanosomes (involved in the keratinocytes) are. Oligoribonucleotide according to claim 2, characterized in that that the structure involved in the actual melanin synthesis the enzyme Tyrosinase, TRP1, TRP2 or the p-protein is. Oligoribonucleotide according to claim 2, characterized in that that the on the expression of the structure involved in melanin synthesis the transcriptin factor is MITF. Oligoribonucleotide according to claim 2, characterized in that that the structure of proteinase Activated involved in the transfer of melanosomes Receptor 2 (PAR-2) is. Oligoribonucleotide according to one of claims 1 to 5, characterized in that it the expression of the gene at the pigmentation of skin and / or Hair involved structure inhibited by at least 25%. Oligoribonucleotide according to Claim 6, characterized that it the expression of the gene at the pigmentation of skin and / or Hair involved structure inhibited by at least 50%. Oligoribonucleotide according to one of claims 1 to 7, characterized in that it before the target sequence based on a length of 20 base pairs in maximum 0 to 2 base pairs deviates. Oligoribonucleotide according to one of claims 1 to 8, characterized in that it a length from 15 to 49 base pairs. Oligoribonucleotide according to Claim 9, characterized that one length of 19 to 25 base pairs. Oligoribonucleotide according to one of claims 1 to 10, characterized in that it homologous to a section of the gene at the pigmentation of Skin and / or hair involved structure is its sense strand 5'-sided through two adenosine residues and 3 'sides by two thymidine residues or by a thymidine and a cytosine residue flanked. Oligoribonucleotide according to one of claims 1 to 11, characterized in that it at the 3'-end two Carries deoxythymidine residues. Oligoribonucleotide according to one of claims 1 to 12, characterized in that it one or more times integrated into an expression vector. Oligoribonucleotide according to one of claims 1 to 13, characterized in that a or more phosphate groups by phosphorothioate, methylphosphonate and / or phosphoramidate groups. Oligoribonucleotide according to one of claims 1 to 14, characterized in that a or more ribose residues by amino acid residues or morpholine residues are exchanged. Oligoribonucleotide according to one of claims 1 to 15, characterized in that a or several ribose radicals modified by fluorine, alkyl or O-alkyl radicals are. Oligoribonucleotide according to one of claims 1 to 16, characterized in that it contains one or more alpha nucleosides. Pharmaceutical or cosmetic composition containing one or more oligoribonucleotides according to one the claims 1 to 17 or a physiologically acceptable salt thereof. Composition according to claim 18 for topical application. A composition according to claim 18 or 19, characterized characterized in that they contains several oligoribonucleotides, the expression of several different at the pigmentation inhibit structures involved in skin and / or hair. A composition according to claim 18 or 19, characterized characterized in that they contains several oligoribonucleotides, the different sequence areas of one and the same gene the actual melanin synthesis (melanosome structures, tyrosis, TRP-1, TRP-2, p-protein) and / or expression of these melanosome structures (MITF) and / or the transfer of the melanosomes (into the keratinocytes) involved structure (PAR-2). A composition according to any one of claims 18 to 21, characterized in that 0.00001 to 10 wt .-% oligonucleotide contains. A composition according to any one of claims 18 to 22, characterized in that Contains 1 to 5 different oligoribonucleotides. A composition according to any one of claims 18 to 23, characterized in that exclusively contains such oligoribonucleotides, the expression of one or more of the pigmentation of the skin and inhibit Harren involved structures. A composition according to any one of claims 18 to 25, characterized in that in the form of a solution, Cream, ointment, lotion, hydrodispersion, lipodispersion, emulsion, Pickering emulsion, gel, solid stick or aerosol is present. Use of an oligoribonucleotide or a physiologically compatible A salt thereof or a preparation according to any one of the preceding claims Skin care or cosmetic or therapeutic treatment of undesirable Pigmentation of the skin or hair. Use of an oligoribonucleotide or a physiologically compatible A salt thereof or a preparation according to any one of the preceding claims Preparation of a cosmetic or therapeutic composition for topical application. Use of an oligoribonucleotide or a physiologically compatible Salt thereof according to claim 1 to 17 for the preparation of a cosmetic or therapeutic agent for skin care or treatment of undesirable Pigmentation of the skin or hair. Use according to any one of claims 27 to 28 for the treatment of changes or damage with respect to the pigmentation on the skin or hair caused by UV radiation in the skin, dryness, roughness and slackness of the skin, wrinkling, reduced refatting Sebaceous glands, and an increased susceptibility to mechanical stress (cracking), for the treatment of photodermatoses, the symptoms of senile xerosis, photoaging and a degradation of the connective tissue of the skin, which are associated with unwanted pigmentation of the skin or hair.