DE102004007032A1 - Antisense oligonucleotides hybridizing with mRNA or a gene sequence to code structures inhibiting skin or hair pigmentation act in melanine synthesis, expression of melanosome structures and/or melanosome transfer - Google Patents

Abstract

An oligonucleotide or physiologically-compatible salt able to hybridize with mRNA or a gene sequence to code one or more structures involved in skin or hair pigmentation takes part in (a) actual melanine synthesis; and/or (b) expression of melanosome structures; and/or (c) melanosome transfer (in the keratinocytes). An independent claim is also included for a pharmaceutical or cosmetic composition containing the oligonucleotide or physiologically-compatible salt. ACTIVITY : Dermatological; Keratolytic No biological data is given. MECHANISM OF ACTION : Melanine synthesis inhibitor; Melanosome structure expression inhibitor; Melanosome transfer inhibitor.

Description

The This invention relates to compositions containing antisense oligonucleotides, which are suitable for the treatment and prophylaxis of unwanted skin pigmentation (skin tanning), as it occurs for example as a result of UV irradiation. In the same way The present invention relates to undesirable pigmentation of 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 under participation 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 on the one hand only after several weeks of application show their effect, the excessively long use on the other hand is of concern 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 because of possible irrever Sibler changes in the pigmentation system of the skin is very controversial. 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 in the beginning (= anagen) phase, which is cyclical Repeated hair formation onion layered as a result of constant neoplasm 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 used. 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 applied under gentler conditions, but their disadvantage lies in the fact that the dyes 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.

The WO 01/58918 A2 describes oligonucleotides with 7 to 25, in particular 20 nucleic acids, which hybridize to a gene encoding an enzyme, the Tyrosinase or TRP-1 and the use of such oligonucleotides.

Mehta et al., The Journal of Investigative Dermatology 115 (2000) 805, describe the treatment of psoriasis by inhibiting expression of the intercellular Adhesion Molecule-1 (ICAM-1), whose expression is increased in psoriatic plaques and therefore as a attractive destination for Psoriasis treatment is considered with Phosphothioatantisenseolgonukleotiden.

The Use of antisense oligonucleotides for prophylaxis and treatment of unwanted pigmentation of skin and hair as well as preparations containing such not yet described, apart from those described in WO 01/58918 A1 Structures Tyrosinase and TRP1.

Hereinafter, the enzymes and proteins involved in the pigmentation of skin and hair are also collectively called "structures involved in the pigmentation (of skin and hair)." Structures involved in the pigmentation include, in particular, those which influence melanogenesis, including Accordingly, the transcription factor MITF and in particular the melanocyte-specific M isoforms (MITF-M) and especially the p-protein (OCA2):
MITF (ID O75030)
MITF-M1 (ID O75030-9)
MITF-M2 (ID O75030-10)
and particularly
P protein (ID Q04671).

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.

• (I) der eigentlichen Melanin-Synthese (Melanosomenstrukturen) und/oder an der
• (II) Expression dieser Melanosomen-Strukturen und/oder am
• (III) Transfer der Melanosomen (in die Keratinozyten) beteiligt sind, den Nachteilen des Standes der Technik abhilft.

It has surprisingly been found that an oligonucleotide or a physiologically acceptable salt thereof which is able to hybridize with an mRNA or a gene sequence which code for one or more structures involved in the pigmentation of the skin and / or the hair, these structures involved in pigmentation of the skin and / or hair

• (I) the actual melanin synthesis (melanosome structures) and / or at the
• (II) expression of these melanosome structures and / or on
• (III) transfer of the melanosomes (into which keratinocytes) are involved, remedies the disadvantages of the prior art.

One such oligonucleotide may have a length of 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 base pairs. Due to this very selective procedure, there is no overlay other physiological processes in the skin. There are very clear Target proteins whose formation is highly selectively prevented. Single The 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.

at the oligonucleotides of the invention are therefore antisense oligonucleotides. In addition to the mentioned oligonucleotides, the invention also physiological compatible Salts of such oligonucleotides suitable. The following is the simplicity half the term oligonucleotide for both the oligonucleotides themselves as well as for their salts used, unless otherwise specified. The term Oligonucleotide closes also modified forms of DNA and RNA.

It has also been found that it is preferred if those on the pigmentation of the skin and / or involved in the hair structures involved in (I) the actual melanin synthesis (melanosome structures) and / or the (II) expression of these melanosome structures and / or the (III) transfer of melanosomes (in the keratinocytes). This has the advantage of a particularly effective effect. The pigmentation of the skin and hair can be roughly divided into the three processes I-III. The more you inhibit individual steps, the better the overall result, since 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 antisense approach is highly selective.

It is preferred when the oligonucleotide has a length of 21, 22, 23 or 24 Has base pairs. It is particularly preferred if the at the structure involved in the synthesis of melanin, the enzyme tyrosinase, TRP1 or TRP2 and especially the p-protein. Also very special it is preferred if those involved in the expression of melanin synthesis involved structure of the transcriptin factor MITF.

The The invention also encompasses pharmaceutical or cosmetic compositions for topical application containing one or more such oligonucleotides contain.

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)

at Tyrosinase (Tyr, Tyro) is the pacemaker enzyme the 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 increases the brown DHICA or, exclusively under the influence of tyrosinase, the black DHI melanin is formed. At the given numbers these are the Accession Numbers of 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, it is MITF-accurate MITF-M- is 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.

Accordingly, among the most preferred structures that influence melanogenesis are the transcription factor MITF, and in particular the melanocyte-specific M isoforms (MITF-M) and in particular the p-protein (OCA2):
MITF (ID O75030)
MITF-M1 (ID O75030-9)
MITF-M2 (ID O75030-10)
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)) in particular:
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.

It is particularly preferred when the one or more oligonucleotides with a or more of the sequences SequenceName 1 to SequenceName 12 hybridized can, with the region of nucleotide 1381 at downstream, the region of nucleotide 121 to 1380, the translation initiating region (region of nucleotide 121 to 453), the region of nucleotide 120 upstream and / or the region adjacent to the start sequence (region of nucleotide 121 to 150), the target sequence "Human 075030 "MAO-TF" "(NCBI Acc: NM_000248) can.

It is furthermore particularly preferred if the oligonucleotide or oligonucleotides with one or more sequences SequenceName 13 through SequenceName 24 can be hybridized and / or with the region of nucleotide 2570 downstream, the Region from nucleotide 53 to 2569, the translation initiating region (Region of nucleotides 53 to 169), the region of nucleotide 52 upstream and / or the region adjacent to the start sequence (region of nucleotide 53 to 85) "Human 004671 "p Protein "" (EMBL ID: HSPPRO AC M99564).

Prefers is an oligonucleotide that the Expression of the gene at the pigmentation of skin and / or hair structure inhibited by at least 25%, more preferably by at least 50%, most preferably by at least 80% and quite extraordinary preferably inhibit by at least 85%. If necessary, will to measure inhibition, expression 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 used suitable primary cultures become. 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.

It in each case those oligonucleotides are preferred which are 3'- or 5'-untranslated Region, the open reading frame, the translation initiating region or the region of the genes adjacent to the start sequence corresponding regions of the mRNA of the genes of said enzymes are complementary.

The Compositions of the invention can contain one or preferably more oligonucleotides. in this connection they may be oligonucleotides that interact with the gene sequences or mRNAs of several different skin pigmentation modulating structures and / or with different sequence regions one and the same gene or mRNA from different hybridize the pigmentation of the skin modulating structures can.

in the Case of MITF are oligonucleotides that target one or more of sequences SequenceName 1 to 12, preferably, in Case of p-protein oligonucleotides targeting one or more sequences SequenceName 13 to 24 are addressed.

All particularly preferred are compositions each at least contain an oligonucleotide directed against MITF and the p-protein is.

Particularly suitable are those oligonucleotides which at 27 to 47 ° C, preferably at 27 to 37 ° C and most preferably at 32 ° C, at a pH of 4 to 9, preferably 5 to 8 and at physi osmolarity, salt and electrolyte concentration specifically hybridize with the said genes or gene segments or their mRNAs.

The according to the invention based on 20 bases, preferably at most 0 to 8, particularly preferred 0 to 4, and most preferably 0 to 2, very extraordinary especially prefers no mismatches. This has the advantage a special effectiveness, because this with the degree of agreement increases with the target sequence.

Bevorzut it is also when the oligonucleotide according to the invention homologous to a section of the gene of the pigmentation of the skin and / or Hair involved structure is whose sense strand is 5'-sided by two Adenosine residues and 3'-sided by two thymidine residues or by a thymidine and a cytosine residue flanking, especially preferred when it carries two deoxythymidine residues at the 3 'end.

It has surprisingly proved that the in the compositions of the invention contained antisense oligonucleotides after application to the Skin with the genes or mRNAs responsible for structures that cause the pigmentation processes in the Skin, encode, hybridize and so on by intervention the expression of the structures involved in the pigmentation of the skin modulate, i. the transcription and / or translation of these enzymes, especially of alternative splice forms, direct and specific inhibit and prevent skin pigmentation without side effects and in this way an effective treatment and prophylaxis of pigmentation enable without showing the disadvantages of the prior art.

The oligonucleotides according to the invention can in the form of oligoribo- or oligodeoxyribonucleotides. Preferably, however, they are oligonucleotides based on the level of sugar residues, the nucleobases, the phosphate groups and / or the skeleton therebetween be chemically modified, for example, the stability the oligonucleotides in the cosmetic or dermatological preparation and / or increase in the skin, e.g. across from a nucleolytic degradation to the penetration of the antisense oligonucleotides to improve the skin and the cell to increase the effectiveness of Antisense oligonucleotides favorable to influence and / or the affinity to be hybridized Sequence sections to improve.

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

preferred Sugar modifications involve the replacement of one or more Ribose or deoxyribose residues of the oligonucleotide by morpholine rings (morpholine oligonucleotides) or by amino acids (peptide oligonucleotides). Preferably, all Ribose or deoxyribose residues of the oligonucleotide against amino acid residues and in particular morpholine residues exchanged.

B steht für eine modifizierte oder nicht modifizierte Purin- oder Pyrimidinbase, vorzugsweise für Adenin, Cytosin, Guanin, oder Uracil,
X steht für O oder S, vorzugsweise O,
Y steht für O oder N-CH3, vorzugsweise O,
Z steht für Alkyl, O-Alkyl, S-Alkyl, NH2, NH(Alkyl), NH(O-Alkyl), N(Alkyl)2, N(Alkyl)(O-Alkyl), vorzugsweise N(Alkyl)2, wobei Alkyl für lineare oder verzweigte Alkylgruppen mit 1 bis 6 vorzugsweise 1 bis 3 und besonders bevorzugt 1 oder 2 Kohlenstoffatomen steht.Particularly preferred are morpholinoligonucleotides in which the morpholine radicals are linked together via sulfonyl or preferably phosphoryl groups, 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-CH3, 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, wherein alkyl represents 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 section of an oligonucleotide chain represents.

All Particularly preferred are morpholinoligonucleotides in which the Morpholine residues over Phosphoryl groups are linked together, as shown in formula 2 is where X for O, Y for O and Z are N (CH 3) 2 stands.

Farther can the ribose or deoxyribose residues are modified by fluorine, alkyl or O-alkyl radicals. Exemplary modifications are 2'-fluoro, 2'-alkyl, 2'-O-alkyl, 2'-O-methoxyethyl modifications, 5'-palmitate derivatives and 2'-O-methylribonucleotides.

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.

As well can Oligonucleotides containing α-nucleosides can be used. Thereby The oligonucleotides are 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 oligonucleotides as well as further suitable modification options are described in the literature. In addition, the production is modified and unmodified oligonucleotides now also of numerous Companies offered as a service, morpholinoligonucleotides e.g. Gene Tools, One Summerton Way, Philomath, OR 97370, USA; Phosphothioatoligonukleotide e.g. from Biomol GmbH, Waidmannstrasse 35, 22769 Hamburg.

Prefers it is when the oligonucleotide of the invention one or more times integrated into an expression vector.

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

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

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

The Compositions of the invention preferably contain from 0.00001 to 10% by weight, more preferably 0.0003 to 3 wt .-% and most preferably 0.01 to 1.0 of or the oligonucleotides according to the invention, based on the total weight of the composition. When using of oligonucleotides integrated into vectors relates the above quantity indication on the mass of the integrated into the vector Oligonucleotides, the mass of the vector itself is not taken into account.

Also it is preferred if such a composition comprises a plurality of oligonucleotides contains 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).

All particularly preferred are compositions of oligonucleotides, which are directed against the expression of MITF and / or the p-protein are.

Compositions according to the invention can also preferably contain 1 to 5 different oligonucleotides, preferred exclusively contains such oligonucleotides, the expression of one or more of the pigmentation of the skin and inhibit Harren involved structures.

Such Compositions are preferably in the form of a solution, cream, Ointment, lotion, hydrodispersion, lipodispersion, emulsion, Pickering emulsion, a gel, a solid stick or as an aerosol.

Also the use of a described oligonucleotide or a physiological compatible salt thereof or a described preparation for the preparation of a cosmetic or therapeutic composition for topical Application is encompassed by the invention.

The Oligonucleotides 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, dryness, roughness and slackness the skin, wrinkling, decreased lipid greasing, and an increased susceptibility across from 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 with undesirable Pigmentation of the skin or hair. The compositions of the invention can Prevent pigmentation defects and existing (defective) pigmentation permanently and without the risk of side effects. For determination the activity of the oligonucleotides according to the invention can be, for example the method described in WO02 / 053773 can be used.

The oligonucleotides 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 the oligonucleotides of the invention are suitable for the prevention and treatment of sun exposure as well as skin tanning also for lightening the pigmentation of the hair. Likewise, the is suitable oligonucleotides according to the invention for lightening a pigmentation which is in itself appropriate to the skin type.

Due to their prophylactic effect oligonucleotides and compositions of the invention are also excellent for skin care and for the preparation of a 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 in terms of Pigmentation on the skin or hair caused by UV radiation in the skin, dryness, roughness and flabbiness 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.

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 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.

Furthermore, the compositions according to the invention are suitable for the treatment of skin damage caused by UV rays, for example the ultraviolet part of the solar radiation. 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) can cause irritation of photosensitive skin and cause damage to the elastic and collagen fibers of the connective tissue, causing the skin to prematurely age. In addition, they are the cause of numerous phototoxic and photoallergic reactions. The oligoribonucleotides according to the invention are also suitable for the treatment of, for example, caused by UV rays structural damage and dysfunction of the epidermis and dermis of the skin, such as visible vascular dilations, such as telangiectases and cuperosis, skin flaccidity and formation of wrinkles, local hyper-, hypo- and Fehlpigmentierungen , such as As age spots, and increased susceptibility to mechanical stress, such as cracking 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 of the invention preferably contain from 0.001 to 35 wt .-%, more preferably From 2 to 15% by weight of emulsifier, from 0.001 to 45% by weight, more preferably 10 to 25% by weight of lipid and 10 to 95% by weight, more preferably 60 to 90% by weight of 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 the different residues are 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 Polyethylenglycolglycerinfettsäureester, 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-) _n -H, 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 ', the etherified fatty acid propoxylates of the general formula R-COO-X _n - Y _m -R ', the fatty acid ureethoxylate / 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 (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, As the ethoxylated alkyl ether or their salt, the sodium laureth-11-carboxylate can be used advantageously.

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.

Especially advantageous W / O emulsifiers are glyceryl monostearate, glyceryl monoisostearate, Glyceryl monomyristate, glyceryl monooleate, diglyceryl monostearate, Diglyceryl monoisostearate, propylene glycol monostearate, propylene glycol monoisostearate, Propylene glycol monocaprylate, propylene glycol monolaurate, sorbitan monoisostearate, Sorbitan monolaurate, sorbitan monocaprylate, sorbitan monoisooleate, Sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol, Behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol, Polyethylene glycol (2) stearyl ether (steareth-2), glyceryl monolaurate, Glyceryl monocaprinate, 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 substances or mixtures of substances which impart to cosmetic or dermatological preparations according to the property (also called trans e pidermal w ater l oss (TEWL)) after the application or distribution on the skin surface, the moisture release of the stratum corneum to reduce and / or Hydration of the horny layer to influence positively. 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. Hyaluronic acid and / or a fucose-rich polysaccharide, for example, which are filed in the Chemical Abstracts 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%, used.

The cosmetic compositions may advantageously also comprise one or more of the following natural active ingredients or a derivative thereof: alpha-lipoic acid, phytoene, D-biotin, coenzyme Q10, alpha-glucosylrutin, carnitine, carnosine, natural and / or synthetic isoflavonoids, creatine, hops or hop-malt extract, taurine. Thus it has been shown that active ingredients for the positive influence on the aging skin, which reduce the development of wrinkles or existing wrinkles, such as biochinones and in particular ubiquinone Q10, soy, creatinine, creatine, liponamide, or the restructuring of the connective tissue, such as isoflavone, in the formulations according to the invention can be used very well. It has also been shown that the formulations are particularly suitable for combination with active ingredients in support of the skin radio tions in dry skin, especially age-dry skin, such as serinol and osmolytes, eg taurine, are suitable. Similarly, the incorporation of drugs to alleviate or positively affect irritative skin conditions, whether sensitive skin in general or noxa-irritated skin (UV light, chemicals), has been found to be beneficial. Here are agents such as sericosides, various extracts of licorice, licochalcone, in particular licochalcone A, silymarin, silyphos, dexpanthenol, inhibitors of prostaglandin metabolism (in particular cyclooxygenase) and leukotriene metabolism (in particular 5-lipoxygenase, but also 5-lipoxygenase Inhibitor protein, FLAP). The incorporation of modulators of pigmentation also proved to be advantageous. Here are agents that reduce the pigmentation of the skin and thus lead to a cosmetically desired lightening of the skin and / or reduce the occurrence of age spots and / or lighten existing age spots (tyrosine sulfate, dioic acid (8-hexadecene-1,16- dicarboxylic acid), lipoic acid and lipoamide, 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-methoxyphenyl)-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. Especially preferred are 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxy] -phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (INCI: aniso triazine), which is available under the trade name Tinosorb ^® S from CIBA-Chemikalien GmbH, and the 4,4 ', 4''- (1,3,5-triazine-2,4,6-triyltriimino) tris-benzoic acid tris (2-ethylhexyl ester), synonymous: 2,4,6-tris [anilino (p-carbo-2'-ethyl-1'-hexyloxy)] - 1,3,5-triazine (INCI: Octyl Triazone), which is 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, dartellt,
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.

Advantageous For the purposes of the present invention are also the 2,4-bis - {[4- (3-sulfonato) -2-hydroxy-propyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3 , triazine-5 Sodium salt containing 2,4-bis - {[4- (3- (2-propyloxy) -2-hydroxy-propyloxy) -2-hydroxy] -phenyl} -6- (4-methoxyphenyl) -1,3,5 triazine, 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] -phenyl} -6- [4- (2-methoxyethylcarboxyl) -phenylamino] -1,3,5-triazine . the 2,4-bis - {[4- (3- (2-propyloxy) -2-hydroxypropyloxy) -2-hydroxy] -phenyl} -6- [4- (2-ethylcarboxyl) -phenylamino] - 1,3,5-triazine, 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] -phenyl} -6- (1-methylpyrrol-2-yl) -1,3,5-triazine 2,4-bis - {[4-tris (trimethylsiloxy-silylpropyloxy) -2-hydroxy] -phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine, the 2,4-bis - {[ 4- (2 '' - methylpropenyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine and 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- (2N-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 to use polymer-bound or polymeric UV filter substances in Preparations according to the present invention, in particular those as described in WO-A-92/20690.

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 Uvasorb K2A ^® is available, for example under trade designation of Han, and hydroxybenzophenones, such as in particular 2- (4'-diethylamino-2'-hydroxybenzoyl) benzoate, or also 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 the 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 also advantageously 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 (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 n TiO ₂ + m (RO) ₃ Si-R '→ n TiO ₂ (surface) is produced. n and m are stoichiometric parameters to be used as desired, 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 re 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 undecylenate; Ester carboxylic acids, for example, calcium stearoyl lactylate, laureth-6 citrate, and sodium PEG-4 lauramide carboxylate; Ether carboxylic acids, for example sodium laureth-13 carboxylate and sodium PEG-6 cocamide carboxylate;
Carboxylic acids, ester carboxylic acids and ether carboxylic acids preferably contain 1 to 50 and in particular 2 to 30 carbon atoms.

Phosphoric acid esters and salts such as DEA-oleth-10-phosphate and dilaureth-4-phosphate;
Sulfonic acids and salts such as (1) acyl isethionates, 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 _12-13 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 from the group of quaternary ammonium compounds, in particular Benzyltrialkylammoniumchloride or bromides, such as benzyldimethylstearylammonium chloride, furthermore alkyltrialkylammonium salts, for example cetyltrimethylammonium chloride or bromide, alkyldimethylhydroxyethylammonium chlorides or bromides, Dialkyldimethylammonium chlorides or bromides, Alkylamidethyltrimethylammoniumethersulfate, Alkylpyridinium salts, for example lauryl or cetylpyrimidinium chloride, Imidazoline derivatives and compounds with cationic character such as Amine oxides, for example alkyldimethylamine oxides or alkylaminoethyldimethylamine oxides. 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 in all this possible in individual cases that the aforementioned concentration data slightly over or be fallen below and still be obtained according to the invention preparations. This comes in the face of the wide variety of suitable Components of such preparations are not unexpected to the person skilled in the art, so he White, that at such over- or underruns the soil of the present invention is not will leave.

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.

Example 1: Preparation of PIT emulsions

By mixing the components listed in the table, phase inversion-temperature (PIT) emulsions of the composition also indicated were prepared. As Oligoribonu kleotid was used ssDNA.

Table 1: PIT emulsions

analog PIT formulations were prepared by the use of MITF (Sequence Name Comp 2) or p-protein (SequenceNameComp 14) antisense oligonucleotides or 0.1% by weight of a mixture of equal parts of Anti-Sequence Name Comp 5, Anti-SequenceNameComp 15 and Anti-SequenceNameComp 18.

Of the Expression of anti-MITF ssDNA (SequenceNameComp 1) or anti-MITF ssDNA (SequenceNameComp 3) denotes MITF antisense oligonucleotides, which hybridize with the sequence SequenceName 1 or SequenceName 3. The remaining used in this and the other examples used terms for the Oligonucleotides are to be understood analogously.

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)

Example 3: Production of water-in-oil emulsions

By mixing the components listed in the table, water-in-oil emulsions of the also stated composition.

Table 3: W / O emulsions

Table 3: W / O Emulsions (continued)

analog Emulsions were prepared by the use of p-protein (SequenceName-Comp 13 and 14) or 0.1% by weight of a mixture of equal parts of Sequence-Name Comp 2, 5 and 7 and SequenceNameComp 13 and 14.

Example 4: Preparation of hydrodispersions

By Mixing of the components listed in the table were hydrodispersions the composition also indicated.

Table 4: Hydrodispersions

analog Emulsions were prepared by the use of p-protein (SequenceName-Comp 13 and 15) or 0.1% by weight of a mixture of equal parts of Sequence-Name Comp 1, 2 and 5 and SequenceNameComp 13 and 15.

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 was subsequently added set to 6.0.

Table 5: Gel cream

analog Gel creams were prepared by using MITF (Sequence Name Comp 2, 3 and 5) or pProtein (SequenceNameComp 13, 16 and 17) antisense oligonucleotides or 0.1% by weight of a mixture of equal parts of SequenceNameComp 13, 16, and 17, and SequenceNameComp 2, 3, and 5.

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

analog Creams were prepared by using MITF (SequenceNameComp 1, 2, 5 and 7 or p-protein (SequenceNameComp 14, 15 and 19) antisense oligonucleotides or 0.1 wt .-% of a mixture of equal parts of these antisense oligonucleotides receive.

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.

Table 7: W / O / W cream

analog Creams were made by using the MITF antisense oligonucleotides (SequenceNameComp 1 and 5) or 0.1% by weight of a mixture of the same Split at SequenceNameComp 13 and 21 and SequenceNameComp 1 and 5 received.

pictures

The 1 shows under (A) the mRNA sequence of the transcription factor MITF (Human 075030 "MOA-TF" NCBI Acc: NM_000248). The transcription factor MITF is one of the most preferred genes. The specific target sequences for the particularly preferred antisense oligonucleotides (as ssDNA oligonucleotides, 25mers) against the transcription factor MITF are listed under (B).

1

(A) Target Sequence: Human 075030 "MOA-TF"

(B) "antiMITF" antisense sequences:

The 2 shows the actual ssDNA oligonucleotides to be used, which consist of the in 1 sequences SequenceName 1-12. At the in 1 The sequences shown are the (mRNA) sequences against which the ssDNA oligonucleotide should be directed to suppress the expression of MITF.

consequently the ssDNA oligonucleotide sequence must be complementary to the SequenceName sequence. These complementary ssDNA, which results from the respective SequenceName sequence, is called SequenceNameComp.

By way of example, this should be shown using the sequence SequenceName 1: SequenceName 1 5 'ggatacctt gtttatagta ccttct 3' SequenceNameComp 1 5 'agaaggtac tataaacaag gtatcc 3'

The 3 shows under (A) the p-protein mRNA sequence (target sequence: Human Q04671 "P PROTEIN" EMBL ID: HSPPRO; AC M99564). The p-protein is one of the most preferred genes. The specific target sequences for the particularly preferred antisense oligonucleotides (as ssDNA oligonucleotides, 25mers) against the p-protein are listed under (B).

3

(A) Target sequence: Human Q04671 "P PROTEIN"

(B) "anti-p-protein" antisense sequences:

The 4 shows the actual ssDNA oligonucleotides to be used, which consist of the in 3 sequences SequenceName 13-24. At the in 3 The sequences shown are the (mRNA) sequences against which the ssDNA oligonucleotide is to be directed in order to suppress the expression of the p protein. Consequently, the ssDNA oligonucleotide sequence must be complementary to the SequenceName sequence. This complementary ssDNA, which results from the respective sequence-name sequence, is called SequenceNameComp.

By way of example, this should be shown using the sequence SequnceName 13: SequenceName 13 5 'ctcctgga gaaagatctg caagtgc 3' SequenceNameComp 13 5 'gcacttgc agatctttct ccaggag 3'

SEQUENCE LISTING

Claims (28)

Oligonucleotide or a physiologically acceptable Salt thereof capable of having an mRNA or a gene sequence to hybridize to one or more of the pigmentation of the Skin and / or hair involved structures encode, these structures involved in the pigmentation of the skin and / or hair at (I) the actual melanin synthesis (melanosome structures) and / or at the (II) Expression of these melanosome structures and / or on (III) transfer of melanosomes (into keratinocytes) involved. Oligonucleotide according to Claim 1, characterized that the on the expression of the structure involved in melanin synthesis the transcriptin factor is MITF. Oligonucleotide according to one of the preceding claims, characterized characterized in that it with one or more sequences SequenceName 1 to SequenceName 12 can hybridize. Oligonucleotide according to one of the preceding claims, characterized characterized in that it With the region of nucleotide 1381 at downstream, of the Region from nucleotide 121 to 1380, the region of nucleotide 121 to 453, also referred to as Translation Initiating Region, of the Region of nucleotide 120 upstream, the region of nucleotide 121 to 150 and / or the start sequence adjacent region each based on the target sequence "Human 075030 "MAO-TF" "(NCBI Acc: NM_000248) can. Oligonucleotide according to claim 1, characterized that the on the expression of the structure involved in melanin synthesis the p-protein is. Oligonucleotide according to claim 5, characterized in that that it with one or more sequences SequenceName 13 through SequenceName 24 can hybridize. An oligonucleotide according to claim 5 or 6, characterized in that it has the region of nucleotide 2570 at the downstream, the region from nucleotide 53 to 2569, the region from nucleotide 53 to 169, also referred to as the translation initiating region, the region of nucleotide 52 at upstream, the region of nucleotide 53 to 85 and / or the start sequence adjacent each region based on the target sequence "human 004671", "p protein" (EMBL ID: HSPPRO AC M99564) can hybridize. Oligonucleotide according to one of the preceding claims, characterized characterized in that it the expression of the gene at the pigmentation of skin and / or Hair involved structure inhibited by at least 25%. Oligonucleotide according to one of the preceding claims, characterized characterized in that it the expression of the gene at the pigmentation of skin and / or Hair involved structure inhibited by at least 50%. Oligonucleotide according to one of the preceding claims, characterized characterized in that it before the target sequence based on a length of 20 base pairs in maximum 0 to 2 base pairs deviates. Oligonucleotide according to one of the preceding claims, characterized 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 by two Adenosine residues and 3'-sided by two thymidine residues or by a thymidine and a cytosine residue flanked. Oligonucleotide according to one of the preceding claims, characterized characterized in that it at the 3'-end two Carries deoxythymidine residues. Oligonucleotide according to one of the preceding claims, characterized characterized in that it one or more times integrated into an expression vector. Oligonucleotide according to one of the preceding claims, characterized characterized in that a or more phosphate groups by phosphorothioate, methylphosphonate and / or phosphoramidate groups. Oligonucleotide according to one of the preceding claims, characterized characterized in that a or more ribose or deoxyribose residues by amino acid residues or morpholine residues are exchanged. Oligonucleotide according to one of the preceding claims, characterized characterized in that a or more ribose or deoxyribose residues by fluorine, alkyl or O-alkyl radicals are modified. Oligonucleotide according to one of the preceding claims, characterized characterized in that it contains one or more alpha nucleosides. Pharmaceutical or cosmetic composition containing one or more oligonucleotides according to one of the preceding claims or a physiologically tolerable Salts thereof. Composition according to claim 20 for topical use. A composition according to claim 20 or 21, characterized characterized in that they contains several oligonucleotides, the expression of several different at the pigmentation inhibit structures involved in skin and / or hair. A composition according to claim 20 or 21, characterized characterized in that they contains several oligonucleotides, the different sequence areas of one and the same gene the actual melanin synthesis (melanosome structures, tyrosianose) and / or the expression of these melanosome structures (MITF) and / or the transfer of the melanosomes (into the keratinocytes) involved Structure (PAR-2) to the goal. Composition according to one of the preceding claims, characterized characterized in that it is 0.00001 contains up to 10 wt .-% oligonucleotide. Composition according to any one of the preceding claims, characterized in that it contains up to 5 different oligonucleotides. Composition according to one of the preceding claims, characterized characterized in that they exclusively contains such oligonucleotides, the expression of one or more of the pigmentation of the skin and inhibit Harren involved structures. Composition according to one of the preceding claims, characterized characterized in that they in the form of a solution, Cream, ointment, lotion, hydrodispersion, lipodispersion, emulsion, Pickering emulsion, gel, solid stick or aerosol is present. Use of an oligonucleotide or a physiological acceptable 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 one of the preceding claims 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 29 to 30 for the treatment of changes or damages regarding pigmentation on the skin or hair caused by UV radiation in skin, dryness, roughness and slackness the skin, wrinkling, decreased lipid greasing, and an increased susceptibility across from 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 with undesirable Pigmentation of skin or hair are connected.