FR3012811A1 - OLIGOPEPTIDES AND THEIR USES - Google Patents

Abstract

The present invention relates to oligopeptides of formula (I), compositions containing these oligopeptides, their cosmetic use particularly for stimulating hair growth and preventing hair loss but also to improve the appearance of the skin, their use as a medicament, and to improve the healing of the skin and / or scalp or stimulate the regeneration of the skin and / or scalp. Thus, the excellent activity and stability of the oligopeptides of this invention can be advantageously applied to cosmetic and pharmaceutical compositions.

Description

The present invention relates to oligopeptides, compositions containing these oligopeptides, and the cosmetic use of oligopeptides particularly for stimulating hair growth and preventing hair loss, but also for improving the appearance of the skin. . The excellent activity and stability of oligopeptides can be advantageously applied to pharmaceutical compositions, quasi-drugs and cosmetics.

Description of the Prior Art A hair follicle is a unique organ of the skin of a mammal. At the base of a hair follicle is a vesicle or papilla of a dermal cell. The papilla is essential for the normal cycle of a hair follicle and for the growth of the body of the hair. The body of the hair is in the form of a thread that is produced with epithelial cells, which are firmly bonded, loaded with keratin filaments and cohesion proteins of the filaments. The number of human hair reaches about 10-15 tens of thousands, and each hair is periodically lost and produced by repeating a cycle consisting of anagen, catagen and telogen phases. The cycle is repeated over a period of 3 to 6 years, resulting in an average hair fall in the range of 50-100. Currently, the mechanism of hair loss remains to be elucidated in detail but we know that it can be caused by an irregular diet, heavy consumption of drinks and cigarettes, drug abuse, insufficient sleep, excessive stress , birth, menopause, permanent and frequent hair coloring or hormonal imbalance. Human hair retains a certain density by repetition of hair growth and degeneration. However, when hair loss is developed by the causes listed above, the hair on the top of the head or front becomes thin and fragile. When the scalp becomes thin and the hair does not develop normally because of reduced capillarity for too long, part of the hair becomes thinner, shortening the longevity of the hair. As a result, not only are the hair 301 2 8 1 1 2 degenerate, but new hair does not develop anymore, resulting in embrittlement and then hair loss. In male pattern baldness, the hair follicle at the front and top of the scalp is androgen sensitive, and an individual with baldness clinically presents a hair loss with characteristic change from a large hair follicle to a follicle hair more fine and small, so more fragile. On the other hand, about 20% of women experience hair loss with the characteristics of a hair becoming tiny at the top of the scalp, thus implying that women are also subject to baldness. In addition, baldness increases with age. Hair loss can be induced by certain diseases, during the healing mechanism, it is called cicatricial alopecia, or by a lesion caused by burning or compression. Regardless of the cause, hair loss is a real societal phenomenon causing loss of pride and self-esteem, and can induce psychological, relational or even sexual disorders. In order to treat such a phenomenon, even though many substances have been used as medical products so far, there are disadvantages such as too high a price or too many differences in efficiency. Other alternative solutions, such as a wig, hair wick or hair extension, can hide the bald parts of the scalp but do not prevent hair loss or stimulate their growth. In addition, several products for the prevention of hair loss using plant extracts have been placed on the market, in particular products containing extracts of sophore root, pepper, swertia, mulberry bark, shepheardia, ginseng, licorice, peony, rehmannia, fennel seed, dogwood fruit, garlic; or products, added in a composition containing xanthine and growth hormone stimulating hair growth, in order to regulate the cellular metabolism due to an excess of dihydrotestoterone (DHT), and thus prevent hair loss and to promote their regeneration. In addition, hair growth stimulating products containing minerals, vitamins, green tea, and extracts of rosemary, mugwort, and licorice have been developed to stimulate hair formation and growth, nutrients are thus provided and having effects of prevention of hair loss and stimulation of hair growth.

Other products have been developed for male pattern baldness, products in which substances such as vitamin B, vitamin C, vitamin E, nicotinic acid, pantothenic acid, biotin, folic acid are mixed with plant extracts to inhibit the activity of 5-alpha-reductase in the human body, avoiding the formation of dihydrotestosterone. However the effect of these products has been reported as minimal. Korean Patent No. 100796817 discloses a composition for hair growth and prevention of hair loss, in which several human cytokines (eg KGF, aFGF, FGF-10) are produced on a large scale by fermentation processes. using Escherichia coli to develop cosmetic products containing growth factors. But these products have application problems and a high cost due to complex processes of production and purification. In addition, these products do not penetrate the hair barrier because of their high molecular weight. The publication of Korean Patent Application KR20110032587 discloses a peptide derived from FGF10, and a composition containing it for treating hair loss. This composition has a better permeability than the known compositions described above but its main disadvantage is that its stability is insufficient, making it unusable in cosmetic formulations. The object of the present invention is therefore to provide a safe and stable product in a composition, especially a cosmetic composition, in particular for stimulating hair growth and preventing hair loss, but also for improving the appearance of the skin. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to oligopeptides according to formula (I), cosmetic, dermatological or pharmaceutical compositions containing at least one oligopeptide according to formula (I), and their cosmetic use, in particular for stimulating the growth of 301 2 8 1 1 4 hair and avoid hair loss, but also to improve the appearance of the skin, in terms of firmness, elasticity, hydration, and the signs of skin aging. The present invention also relates to oligopeptides according to formula (I) for their use as a medicament, and to improve the healing of the skin and / or scalp or stimulate the regeneration of the skin and / or scalp. An object of this invention is therefore to provide an oligopeptide of formula (I) Ri. - Y - R2, wherein: Y is a peptide of sequence SEQ ID NO: 1 (Leu Gln Glu Gly Val Arg) 10 - Ri is linked to the terminal NH2 group of said peptide and selected from the group consisting of: - H - a linear or branched alkyl carbonyl, alkenylcarbonyl or alkynylcarbonyl group having 1 to 24 carbon atoms, which is functionalized with a -OH, -SH, -COOH or -CONN2-R2 group is the terminal carboxylic group of said peptide, or -COOR3 or CO-NH2, and wherein R3 is selected from the group consisting of: -H - a linear or branched alkyl, alkenyl or alkynyl group having 1 to 24 carbon atoms, which is functionalized with an OH group, -SH, -COOH or -CONH2. The term "peptide" refers to a linear molecule formed by linking amino acid residues via peptide bonds. For the purposes of the present invention, the term "alkyl group" means any linear or branched alkyl group of 1 to 24 carbon atoms, in particular the methyl, ethyl, n-propyl, isopropyl, n-butyl and iso groups. butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octanyl, n-nonyl, n-decanyl, n-undecanyl, n-dodecanyl, n-tridecanyl, n-tetradecanyl, n pentadecanyl, n-hexadecanyl, n-heptadecanyl, n-octadecanyl, n-nonadecanyl, n-eicosanyl, heneicosanyl, n-docosanyl, tricosanyl, n-tetracosanyl. By the term "alkynyl group" is meant in the sense of the present invention any linear or branched alkyl group comprising one or more triple bonds and containing from 2 to 24 carbon atoms. In particular, mention may be made of the ethynyl or propynyl group.

By the term "alkenyl group" is meant in the sense of the present invention any linear or branched alkyl group having 1 or more double bonds and comprising from 2 to 24 carbon atoms. Examples of the alkenyl group are isopropenyl, ethenyl.

For the purposes of the present invention, the term "alkylcarbonyl group" means any alkyl group as defined above bonded via a carbonyl group (C = O). Preferentially, these are acetyl, ethanoyl, propionyl, isopropionoyl, butanoyl, isobutanoyl, decanoyl, lauryl, myristyl, palmitoyl, stearoyl, oleoyl, lipoyl, linoleyl. For the purposes of the present invention, the term "alkenylcarbonyl group" means any alkenyl group as defined above and linked via a carbonyl group (C = O). Examples of alkenylcarbonyl are ethanoloyl, propionoyl, isopropionoyl, butanoleoyl, isobutanoloyl, decaneoyl, lauroleoyl, myristoleoyl, palmitoleoyl, oleoyl, linoleoyl, linolenoyl. For the purposes of the present invention, the term "alkynylcarbonyl group" means any alkynyl group as defined above bonded via a carbonyl group.

Advantageously, the oligopeptides according to the invention are of formula (I) in which R 1 is selected from the group consisting of -H, alkylcarbonyl or alkenylcarbonyl. According to another advantageous embodiment, the oligopeptides according to the invention are of formula (I) in which R 3 is selected from the group consisting of -H, an alkyl or alkenyl group. These two advantageous embodiments can also be combined with each other. R1 is preferably selected from the group consisting of H, acetyl (CH3-00-), ethanoyl (CH3-CH2-CO-), propionyl, isopropionyl, butanoyl (= butyryl, CH3- (CH2) 2-CO -), isobutyryl, decanoyl, lauryl, myristyl, pal mitoyl (CH3- (CH2) 14-00-), stearoyl (CH3- (CH2) 16-00-), oleyl, lipoyl, linoleyl or conjugated linoleyl, and / or R 2 is preferably selected from the group consisting of - CONH 2, -COOR 3, where R 3 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl. More preferably, R 1 is selected from the group consisting of H, and an acetyl group and R 2 is selected from the group consisting of -COOH, and -CONH 2. In one embodiment, the amino terminus is unsubstituted but is an amino group. Within the scope of the invention, in the case where R 1 = H, it is found that the oligopeptide of the invention can be protonated, and may be present in the form of a salt, for example as a chloride, a bromide, fluoride or iodide. According to a preferred embodiment, R1 is even better H, and / or R2 is even better -COOH. Thus, the oligopeptide according to formula (II) NH2-Leu-Gln-Glu-GlyVal-Arg-OH is a particularly preferred embodiment of the invention. The term "oligopeptide" according to the present invention means a single species of formula (I) or mixtures of at least 2, at least 3 or more oligopeptides of formula (I). For the purposes of the present invention, the term "oligopeptide derivative" means the oligopeptide of formula (I) for which R 1 is not H. As used in this specification, the term "oligopeptide" or "oligopeptides" includes oligopeptides, oligopeptide derivatives as well as salts of oligopeptides and salts of oligopeptide derivatives. Such possible salts include sodium, potassium, acetate, trifluoroacetate salts. According to the present invention, the amino acids can exist in either the L-form, the D-form, or the DL-form in the peptide. In a preferred embodiment of the invention, the amino acids are all in the L-form. The peptides of the invention can be prepared by conventional chemical synthesis methods known to those skilled in the art, for example by solid phase synthesis techniques (Merrifield, J. Amer Chem Soc., 85: 2149-54 (1963), Stewart, et al., Solid Phase Peptide Synthesis, 2nd ed., Pierce Chem Co., Rockford, 111 (1984)). They can also be obtained by enzymatic synthesis, by controlled hydrolysis of natural proteins of microorganisms, plants or animals which contain oligopeptides or precursors of oligopeptides according to the invention. Oligopeptides obtained chemically or enzymatically can then be converted into derivatives (for example acetylated) by known chemical or enzymatic techniques to obtain the oligopeptides according to the invention. Oligopeptides can also be produced by microorganisms, which either naturally form the oligopeptides, or may have been genetically modified or otherwise manipulated during fermentation under fermentation conditions such that they form the oligopeptides according to the invention. invention. In the case where the oligopeptides (or their precursors) are obtained by hydrolysis of proteins, the oligopeptides thus obtained can be used in the crude state, or they can be further purified by known techniques (membrane filtration, chromatography, immunoprecipitation ) to obtain the desired oligopeptides. The inventors have found that the oligopeptide (s) according to formula (I) and particularly according to formula (II) stimulate the growth of keratinocytes and fibroblasts, protect keratinocytes from apoptosis, and stimulate follicle growth. hair, but also have the level of stability required for compositions including cosmetics.

The oligopeptides according to formula (I) and particularly formula (II) of the present invention act: on stimulating the growth of keratinocytes, fibroblasts, which can result in an increase in hair growth, an increase in the skin epidermis and the thickness of the dermis, - on the promotion of the lengthening of the hair follicle, which can result in a stimulation of hair growth, a decrease in hair loss, - on the modulation Versican genes, BDNF, BIRC5, MAGED1 and MMP9, whose expressions are involved in the hair cycle, the production of new hair follicles, itching, and skin structure, which can result in stimulation of the skin. hair growth, regeneration of the hair and an improvement of the state of the skin and signs of skin aging, - on the stimulation of the migration of keratinocytes, which may result in an improvement of the regeneration of the hair and the skin, - on an anti-oxidant defense with a keratinocyte protection of an H202-induced cellular apoptosis, which can result in a limitation of the hair loss, the formation gray hair, and limit the effects of aging and the accumulation of oxidative deterioration of hair and skin. Compared to prior solutions for the induction of hair growth, such as the use of the FGF-10 derived peptide as described in KR20110032587, the advantage of specific oligopeptides according to formula (I) and particularly formula (II) according to the invention have excellent stability, solving the major problem of stability of a peptide derived from FGF-10 in particular cosmetic compositions. In the context of the invention, the term "stable" or "stability" is understood to mean the absence of degradation of the oligopeptide, in particular by hydrolysis, when it is present in an aqueous solution and / or in a composition cosmetic for at least 6 months, preferably at least 8 months or at least 12 months, at a temperature ranging from 4 to 45 ° C, preferably at room temperature, ie around 20 ° C. The present invention therefore proposes to provide stable oligopeptides which may be included in a composition for treating or reducing hair loss, but also for improving the condition of the skin and / or the scalp. Another subject of the invention thus relates to a cosmetic, dermatological or pharmaceutical composition comprising at least one oligopeptide as defined above and a cosmetically, dermatologically or pharmaceutically acceptable excipient respectively, preferably topically acceptable. For the purposes of the present invention, the term "cosmetic and / or dermatological topically acceptable", an ingredient suitable for topical application, non-toxic, non-irritating to the skin and / or the scalp, does not induce allergic response, which is not chemically unstable.

According to a preferred embodiment of the present invention, the cosmetic, dermatological or pharmaceutical compositions comprising at least one oligopeptide according to the invention also contain one or more auxiliary compounds or additives.

According to a particularly advantageous embodiment of the invention, the oligopeptides according to the invention are present in a cosmetic composition comprising an acceptable cosmetic excipient. This cosmetic composition is advantageously intended for topical application.

The oligopeptides are advantageously present in the cosmetic composition at a concentration of 0.001 to 10,000 ppm, preferably from 0.01 to 1000 ppm, more preferably from 0.05 to 500 ppm, even more preferably from 0.5 to 100 ppm. In the cosmetic compositions, the oligopeptides of the invention are preferably dissolved or solubilized in one or more solvents which are approved for cosmetic preparations, such as, for example, water, glycerol, propylene glycol, butylene glycol, pentylene glycol, ethoxylated or propoxylated diglycols, ethanol, propanol, isopropanol or mixtures of said solvents.

It is further possible to use solubilized oligopeptides in liposomes or adsorbed to organic polymers, or mineral supports or similar materials which are particularly acceptable for topical application. According to a particularly advantageous embodiment, the oligopeptides are present in a form solubilized in liposomes in the compositions according to the invention, and in particular the cosmetic compositions. Optionally in addition to the solvents, the compositions according to the invention or used according to the invention may also contain one or more auxiliary compounds and additives. The oligopeptides according to the invention may be present in cosmetic compositions, such as, for example, shampoos for the hair, hair lotions, bubble baths, shower products, creams, gels, lotions, alcoholic or hydro-alcoholic solutions, emulsions, wax / grease masses, stick preparations, powders or balms.

These compositions may also comprise, as other auxiliaries and additives, mild surfactants, oily substances, emulsifiers, pearlescent waxes, consistency regulators, thickeners, superfatting agents, stabilizers, polymers, silicone compounds, fats, waxes, lecithins, phospholipids, UV photoprotective factors, biogenic active ingredients, antioxidants, deodorants, antiperspirants, antidandruff agents, film formers, blowing agents, insect repellents, self-tanning agents, tyrosine inhibitors (depigmenting agents), hydrotropes, solubilizers, preservatives, scented oils, dyes and the like. Surfactants The surfactants which may be present are anionic, nonionic, cationic and / or amphoteric or zwitterionic surfactants, the content of which in the compositions is usually from about 1 to 70% by weight, preferably from 5 to 50%. by weight and in particular from 10 to 30% by weight. Typical examples of the anionic surfactants are soaps, alkylbenzene sulfonates, alkane sulfonates, olefin sulfonates, alkyl ether sulfonates, glycerol ether sulfonates, α-methyl ester sulfonates, sulfonates, and the like. fatty acids, alkyl sulphates, alkyl ether sulphates, glycerol ether sulphates, fatty acid ether sulphates, mixed hydroxy ether sulphates, monoglyceride sulphates (ethers), sulphates of fatty acid amides (ethers), mono- and di-alkyl sulfosuccinates, mono- and di-alkyl sulfosuccinates, sulfotriglycerides, amide soaps, carboxylic acid ethers and salts thereof fatty acid isethionates, fatty acid sarcosinates, fatty acid taurides, N-acylamino acids, such as, for example, acyl lactylates, acyl tartrates, acyl glutamates, and acyl aspartates, alkyloligoglusosid sulfates es, fatty acid condensates of proteins (especially wheat-based plant products) and alkyl phosphates (ethers). If the anionic surfactants comprise polyglycol ether chains, they may have a conventional homolog distribution, but they preferably have a narrowed homolog distribution. Typical examples of the nonionic surfactants are polyglycol ethers of fatty alcohols, alkylphenol polyglycol ethers, polyglycol esters of fatty acids, polyglycol ethers of fatty acid amides, polyglycol ethers of fatty amines, alkoxylated triglycerides, mixed ethers and mixed formats, optionally partially oxidized alkyl (alkenyl) oligoglycosides and derivatives of glucoronic acid, N-alkylglucamides of fatty acids, protein hydrolysates (in particular wheat-based plant products) esters of polyols and fatty acids, sugar esters, sorbitan esters, polysorbates and amine oxides. If the nonionic surfactants contain polyglycol ether chains, they may have a conventional homolog distribution, but they preferably have a narrowed counterpart distribution. Typical examples of cationic surfactants are quaternary ammonium compounds, such as, for example, dimethyldistearylammonium chloride, and quaternized esters, especially quaternized fatty acid trialkanolamine ester salts. Typical examples of amphoteric and zwitterionic surfactants are alkylbetaines, alkylaminobetaines, minopropionates, aminoglycinates, imidazoliniumbetaines and sulfobetaines. The surfactants specified are exclusively known compounds. Typical examples of mild surfactants which are particularly suitable, i.e., particularly skin-compatible, are fatty alcohol polyglycol ether sulfates, monoglyceride sulphates, mono- and / or dialkyl sulphosuccinates, fatty acids, fatty acid sarcosinates, fatty acid taurides, fatty acid glutamates, α-olefin sulfonates, carboxylic acid ethers, alkyl oligoglucosides, acid glucosides fatty alcohols, alkylamidomobidates, aminoacetals and / or fatty acid condensates of proteins, the latter being preferably based on wheat proteins. Oily bodies Suitable oily bodies are, for example, Guerbet alcohols based on fatty alcohols having from 6 to 18, preferably from 8 to 10 carbon atoms, linear C6-C22 fatty acid esters with fatty alcohols. C5-C22 linear or branched and / or C5-C13 carboxylic acid esters branched with linear C6-C22 fatty alcohols 301 2 8 1 1 12 or branched, such as for example myristyl myristate, palmitate of myristyl, myristyl stearate, myristyl isostearate, myristyl oleate, myristyl behenate, myristyl erucate, cetyl myristate, cetyl palmitate, cetyl stearate, isostearate, cetyl oleate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl myristate, stearyl palmitate, stearyl stearate, stearyl isostearate, stearyl oleate, behenate stearyl, stearyl erucate, isostearyl myristate isostearyl palmitate, isostearyl stearate, isostearyl isostearate, isostearyl oleate, isostearyl behenate, isostearyl oleate, oleyl myristate, palmitate oleyl stearate, oleyl isostearate, oleyl oleate, oleyl behenate, oleyl erucate, behenyl myristate, behenyl palmitate, oleyl stearate, behenyl, behenyl isostearate, behenyl oleate, behenyl behenate, behenyl erucate, erucyl myristate, erucyl palmitate, erucyl stearate, erucyl isostearate , erucyl oleate, erucyl behenate and erucyl erucate. C6-C22 fatty acid esters linear with branched alcohols, in particular 2-ethylhexanol, esters of C18-C38 alkyl hydroxycarboxylic acids with linear or branched C6-C22 fatty alcohols ( conferring on DE 19756377 A1), in particular dioctyl malates, linear and / or branched fatty acid esters with polyvalent alcohols (such as, for example, propylene glycol, a dimeric diol or a trimer triol) and / or alcohols of Guerbet, triglycerides based on C6-C10 fatty acids, liquid mixtures of mono- / di- / tri-glycerides based on C6-C18 fatty acids, esters of C6-C18 fatty alcohols. C22 and / or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C 2 -C 12 dicarboxylic acids with linear or branched alcohols having 1 to 22 carbon atoms or polyols having from 2 to 10 carbon atoms and from 2 to 6 hydroxyl groups, vegetable oils Examples are: branched primary alcohols, substituted cyclohexanes, linear and branched C6-C22 fatty alcohol carbonates, such as, for example, dicaprylyl carbonate (Cetiol® CC), Guerbet carbonates based on fatty alcohols having from 6 to 18, preferably from 8 to 10 carbon atoms, benzoic acid esters with linear and / or branched C6-C22 alcohols (for example Finsolv® TN), linear or symmetrical dialkyl ethers, linear or branched from 6 to 22 carbon atoms per alkyl group, such as, for example, dicaprylyl ether (Cetiol® 0E), ring-opening products of fatty acid esters epoxidized with polyols silicone oils (cyclomethicones, silicon methicone types, among others) and / or aliphatic or naphthenic hydrocarbons, such as, for example, squalane, squalene or dialkylcyclohexanes are also suitable. Emulsifiers Suitable emulsifiers are, for example, nonionic surfactants from at least one of the following groups: adducts of 2 to 30 moles of ethylene oxide and / or 0 to 5 moles of propylene oxide to linear fatty alcohols having 8 to 22 carbon atoms, to fatty acids having from 12 to 22 carbon atoms, alkylphenols having 8 to 15 carbon atoms in the alkyl group, and alkylamines having 8 to 22 carbon atoms in the alkyl group; . alkyl- and / or alkenyl-oligoglycosides having 8 to 22 carbon atoms in the alkyl (alkenyl) radical and the ethoxylated analogs thereof, 20. adducts of 1 to 15 moles of ethylene oxide to castor oil and / or hydrogenated castor oil; . adducts of 15 to 60 moles of ethylene oxide to castor oil and / or hydrogenated castor oil; . partial esters of glycerol and / or sorbitan with unsaturated, linear or saturated, branched fatty acids having 12 to 22 carbon atoms and / or hydroxycarboxylic acids having 3 to 18 carbon atoms, and the adducts of these with from 1 to 30 moles of ethylene oxide; . partial esters of polyglycerol (average degree of autocondensation 2 to 8), polyethylene glycol (molecular weight 400 to 5,000), trimethylolpropane, pentaerythritol, sugar alcohols (eg sorbitol), alkylglucosides ( for example methylglucoside, butylglucoside, laurylglucoside), and polyglucosides (for example cellulose) with saturated and / or unsaturated, linear or branched fatty acids having 12 to 22 carbon atoms and / or acids 301 2 8 1 1 14 hydroxycarboxylic having from 3 to 18 carbon atoms, and the adducts thereof with from 1 to 30 moles of ethylene oxide; . mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and / or mixed esters of fatty acids having 6 to 22 carbon atoms, methylglucose and polyols, preferably glycerol or polyglycerol,. mono-, di- and tri-alkyl phosphates and alkyl mono-, di- and / or tri-PEG phosphates and salts thereof; . lanolin alcohols; 10. polysiloxane-polyalkylpolyether copolymers and corresponding derivatives; . block copolymers, for example dipolyhydroxystearates of polyethylene glycol-30; . polymeric emulsifiers, for example Pemulen grades (TR-1, TR-2) from Goodrich; . polyalkylene glycols; and. glycerol carbonate. . Ethylene oxide adducts Adducts of ethylene oxide and / or propylene oxide to fatty alcohols, fatty acids, alkylphenols or castor oil are products known commercially available. These are homologous mixtures whose average degree of alkoxylation corresponds to the ratio of the amounts of the ethylene oxide and / or propylene oxide substances to the substrate with which the addition reaction is carried out. . Mono- and di-esters of C12118 fatty acids from ethylene oxide adducts to glycerol are known as gelling agents for cosmetic preparations. . Alkyl- and / or alkenyl-oligoglycosides The alkyl- and / or alkenyl-oligoglycosides, their preparation and their use are known from the prior art. They are prepared in particular by reacting glucose or oligosaccharides with primary alcohols having from 8 to 18 carbon atoms. With regard to the glycoside radical, both the monoglycosides, in which a cyclic sugar moiety is glycoside bonded to the fatty alcohol and the oligomeric glycosides having a degree of oligomerization of up to preferably about 8. , are appropriate. The degree of oligomerization is here a statistical average value which is based on a usual homolog distribution for such technical grade products. . Partial glycerides Typical examples of suitable partial glycerides are hydroxystearic acid monoglyceride, hydroxystearic acid diglyceride, isostearic acid monoglyceride, isostearic acid diglyceride, oleic acid monoglyceride, diglyceride. oleic acid, ricinoleic acid monoglyceride, ricinoleic acid diglyceride, linoleic acid monoglyceride, linoleic acid diglyceride, linolenic acid monoglyceride, linolenic acid diglyceride, sodium monoglyceride. erucic acid, erucic acid diglyceride, tartaric acid monoglyceride, tartaric acid diglyceride, citric acid monoglyceride, citric acid diglyceride, malic acid monoglyceride, acid diglyceride malic, and technical grade mixtures thereof which may also include minor amounts of triglycerides as a minor product of the invention. process of preparation. Adducts of from 1 to 30 moles, preferably from 5 to 10 moles, of ethylene oxide to said partial glycerides are also suitable. 20. Sorbitan Esters Suitable sorbitan esters are sorbitan monoisostearate, sorbitan sesquiisostearate, sorbitan diisostearate, sorbitan triisostearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan dioleate, sorbitan trioleate, sorbitan mono- erucate, sorbitan sesquiérucate, sorbitan dierucate, sorbitan trierucate, sorbitan monoricinoleate, sorbitan sequiricinoleate, sorbitan diricinoleate, sorbitan triricinoleate, sorbitan monohydroxystearate, sodium sesquihydroxystearate, sorbitan, sorbitan dihydroxystearate, sorbitan trihydroxystearate, sorbitan monotartrate, sorbitan sesquitartrate, sorbitan ditartrate, sorbitan tritartrate, sorbitan monocitrate, sorbitan sesquicitrate, sorbitan dicitrate, tricitrate of sorbitan, sorbitan monomaleate, sequimate sorbitan ate, sorbitan dimaleate, sorbitan trimaleate, and technical grade mixtures thereof. Adducts of from 1 to 30 moles, preferably from 5 to 10 moles, of ethylene oxide to said sorbitan esters are also suitable. . Polyglycerol Esters Typical examples of suitable polyglycerol esters are polyglyceryl-2 dipolyhydroxystearate (Dehymuls® PGPH), polyglycerol-3 diisostearate (Lameform® TGI), polyglyceryl-4 isostearate (Isolan® 34), polyglyceryl-3 oleate, diisostearoylpolyglyceryl-3 diisostearate (Isolan® PDI), polyglyceryl-3 methylglucose distearate (Tego Care® 450), polyglyceryl-3 beeswax 10 (Cera Bellina®). ), polyglyceryl-4 caprate (Polyglycerol Caprate T2010 / 90), polyglyceryl-3-cetyl ether (Chimexane® NL), polyglyceryl-3 distearate (Cremophor® GS 32) and polyglyceryl polyricinoleate (Admul® WOL 1403) , polyglyceryl dimerate isostearate, and mixtures thereof. Examples of still suitable polyol esters are the mono-, di- and tri-esters optionally reacted with from 1 to 30 moles of ethylene oxide, trimethylolpropane or pentaerythritol with lauric acid. coconut fatty acid, tallow fatty acid, palmitic acid, stearic acid, oleic acid, behenic acid and the like. 20. Anionic Emulsifiers Typical anionic emulsifiers are aliphatic fatty acids having 12 to 22 carbon atoms, such as, for example, palmitic acid, stearic acid or behenic acid, and dicarboxylic acids having from 12 to 22 carbon atoms. carbon, such as for example azelaic acid or sebacic acid. . Amphoteric and cationic emulsifiers Zwitterionic surfactants can also be used as emulsifiers. The term "zwitterionic surfactants" refers to surfactant compounds which carry at least one quaternary ammonium group and at least one carboxylate group and a sulfonate group in the molecule. Particularly suitable zwitterionic surfactants are the so-called betaines, such as N-alkyl-N, N-dimethylammonium glycinates, for example cocoalkyldimethylammonium glycinate, N-acylaminopropyl-N, N-dimethylammonium glycinates, e.g. cocoacylaminopropyldimethylammonium glycinate, and 2-yl-3-carboxymethyl-3-hydroxyoxyimidazolines having in each case 8 to 18 carbon atoms in the alkyl or alkyl group, and cocoacylaminoethylhydroxyethylcarboxylethyl glycinate. Particularly preferred is the fatty acid amide derivative known as CTFA of cocamidopropyl betaine. Similar suitable emulsifiers are amphoteric surfactants. The term "amphoteric surfactants" denotes surfactant compounds, which contain, apart from a C8118 alkyl or alkyl group, at least one free amino group and at least one -COOH or -SO3H group in the molecule and which are capable of forming internal salts. Examples of suitable amphoteric surfactants are N-alkylglycines, N-alkylaminopropionic acids, N-alkylaminobutyric acids, N-alkyl klymodipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylamines. alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoacetic acids having in each case from about 8 to 18 carbon atoms in the alkyl group. Particularly preferred amphoteric surfactants are N-cocoaalkylamino propionate, cocoacylamidoethylmethylpropionate and a C12 / 18 acyl sarcosine. The cationic surfactants are finally also suitable as emulsifiers, those of the quaternized ester type, preferably the methyl quaternized fatty acid triethanolamine ester salts being particularly preferred. Fats and waxes Typical examples of fats are glycerides, i.e. solid or liquid plant or animal products which consist essentially of mixed glycerol esters of higher fatty acids, the appropriate waxes are inter alia natural waxes, such as, for example, candelilla wax, carnauba wax, Japanese wax, esparto wax, cork wax, guaruma wax, rice germ oil wax, wax sugar cane, uricury wax, mineral wax, beeswax, shellac wax, spermaceti, lanolin (wool wax), uropygial fat, ceresin, ozokerite (earth wax), petrolatum, paraffin waxes, microcrystalline waxes; chemically modified waxes (hard waxes), such as, for example, mineral ester waxes, sasol waxes, hydrogenated jojoba waxes, and synthetic waxes, such as, for example, polyalkylene waxes and polyethylene glycol waxes; . In addition to waxes, suitable additives are also fat-like substances, such as lecithins and phospholipids. The term "lecithins" is understood by those skilled in the art as indicating glycerophospholipids found from fatty acids, glycerol, phosphoric acid and choline by esterification. Lecithins are also often indicated as phosphatidylcholines (PC) in the term of the specialist. Examples of natural lecithins which may be mentioned are cephalins, which are also cited as phosphatidic acids and are derivatives of 1,2-diacyl-sn-glycerol-3-phosphoric acids. In contrast, phospholipids are usually understood to indicate mono- and preferably di-esters of phosphoric acid with glycerol (glycerol phosphates), which are generally classified as fats. Sphingosines and sphinogolipids are also suitable.

Pearlescent Waxes Examples of suitable pearlescent waxes are: alkylene glycol esters, particularly ethylene glycol distearate; fatty acid alkanolamides, specifically coconut fatty acid diethanolamide; partial glycerides, specifically stearic acid monoglyceride; polyvalent carboxylic acid esters optionally hydroxy-substituted with fatty alcohols having from 6 to 22 carbon atoms, specifically long-chain esters of tartaric acid; fatty substances, such as, for example, fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates, which have a total of at least 24 carbon atoms, specifically laurone and distearyl ether; fatty acids, such as stearic acid, hydroxystearic acid or behenic acid, ring-opening products of olefinic epoxides having from 12 to 22 carbon atoms with fatty alcohols having from 12 to 22 carbon atoms and / or polyols having 2 to 15 carbon atoms and 2 to 10 hydroxyl groups, and mixtures thereof. Consistency Regulators and Thickeners Suitable consistency regulators are mainly fatty alcohols or hydroxy fatty alcohols having from 12 to 22, and preferably from 16 to 18 carbon atoms, and also partial glycerides, fatty acids or hydroxy partial fatty acids. A combination of these substances with alkyloligoglucosides and / or N-methylglucamides of fatty acids of identical chain lengths and / or polyglycerol poly-12-hydroxystearates is preferred. Suitable thickeners are, for example, Aerosil qualities (hydrophilic silicas), polysaccharides, in particular xanthan gum, guar-guar, agar-agar, alginates and tyloses, carboxymethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose. and also polyethylene glycol mono-and diesters of relatively high molecular weight fatty acids, polyacrylates (eg Goodrich's Carbopols® and Pemulen grades, Sigma's Synthalens®, Kelco's Keltrol grades, Sepigel grades from Seppic; Salcare grades of Allied Colloids), polyacrylamides, polymers, polyvinyl alcohol and polyvinylpyrrolidone. Bentonites, such as, for example, Bentone® Gel VS 5PC (Rheox), which is a mixture of cyclopentasiloxane, distetardimonium hectorite and propylene carbonate, have also proved to be particularly effective. Also suitable are surfactants, such as, for example, ethoxylated fatty acid glycerides, fatty acid esters with polyols, such as, for example, pentaerythritol or trimethylolpropane, fatty alcohol ethoxylates having a homologous distribution. narrowed or alkyl-oligoglucosides, and electrolytes, such as sodium chloride and ammonium chloride. Supergrading Agents The superfatting agents that can be used are substances such as, for example, lanolin and lecithin, and polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and alkanolamides of fatty acids, the latter also serving as foam stabilizers. Stabilizers The stabilizers that can be used are metal salts of fatty acids, such as, for example, magnesium, aluminum and / or zinc stearate or ricinoleate. Polymers Suitable cationic polymers are, for example, cationic cellulose derivatives, such as, for example, a quaternized hydroxyethylcellulose obtainable under the name Polymer JR 400 from Amerchol, a cationic starch, copolymers of diallylammonium salts. and acrylamides, quaternized vinylpyrrolidone-vinylimidazole polymers, such as, for example, Luviquat® (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides, such as, for example, lauryldimonium hydroxypropyl hydrolysed collagen. (Mequate L / Grünau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers, such as, for example, modimethicones, adipic acid and diethylmethylhydroxypropyldiethylenetria mi copolymers (Cartaretinse / Sandoz ), copolymers of acrylic acid with dimethyldiallylammonium chloride (Merquat® 550 / Chemviron), polyaminopolyamides, as described for example in FR 2252840 A, and crosslinked water-soluble polymers thereof, cationic chitin derivatives, such as, for example, quaternized chitosan, optionally in a microcrystalline dispersion, condensation products of dihaloalkyls, such as for example dibromobutane with bisdialkylamines, such as, for example, bis-dimethylamino-1,3-propane, cationic guar gum, such as, for example, Jaguar® CBS, Celanese Jaguar® C-17, Jaguar® C-16, quaternized ammonium salt polymers, such as for example Mirapol® A-15, Mirapol® AD-1, Mirapol® AZ-1 from Miranol. Suitable anionic, zwitterionic, amphoteric and nonionic polymers are, for example, vinyl acetate-crotonic acid copolymers, vinylpyrrolidone-vinyl acrylate copolymers, vinyl acetate-butyl maleate-acrylate copolymers, and the like. isobornyl, methylvinylether-maleic anhydride copolymers and esters thereof, non-crosslinked poly (acrylic acids) and poly (acrylic acids) crosslinked with polyols, copolymers of acrylamidopropyltrimethylammonium chloride acrylate, octylacrylamide-methyl methacrylate-tert-butylaminoethyl methacrylate-2-hydroxypropyl methacrylate copolymers, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, terpolymers of vinylpyrrolidone-dimethylaminomethyl methacrylate-vinylcaprolactam, and cellulose ethers optionally derived and silicones.

Silicone Compounds Suitable silicone compounds are, for example, dimethylpolysiloxanes, methylphenylpolysiloxanes, cyclic silicones, and amino-, fatty acid-, alcohol-, polyether-, epoxy-, fluor-, glycoside- and / or silicone compounds. alkyl-modified, which may be either liquid or in a resin form at room temperature. Si-methicones, which are mixtures of dimethicones having an average chain length of 200 to 300 dimethylsiloxane units and hydrogenated silicates, are also suitable.

Photoprotective UV filters Photoprotective UV factors are for example to be understood as indicating organic substances (photoprotective filters) which are liquid or crystalline at room temperature and which can absorb ultraviolet radiation and re-release the energy absorbed in the form of longer wavelength radiation, for example heat. UVB filters can be oil soluble or water soluble. Examples of the oil-soluble substances are: 3-benzylidene camphor or 3-benzylidene norcamphor and derivatives thereof, e.g. 3- (4-methylbenzylidene) camphor; . 4-aminobenzoic acid derivatives, preferably 2-ethylhexyl 4- (di methylamino) benzoate, 2-octyl 4- (di methylamino) benzoate and 4- (di methylamido) amine benzoate; 25. cinnamic acid esters, preferably 2-ethylhexyl 4-methoxycinnamate, propyl 4-methoxycinnamate, isoamyl 4-methoxycinnamate, 2-cyano-3,3-phenylamine, and 2-ethylhexyl (octocrylene); . salicylic acid esters, preferably 2-ethylhexyl salicylate, 4-isopropylbenzyl salicylate, homomenthyl salicylate; . benzophenone derivatives, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone; 35. benzalmalonic acid esters, preferably di-2-ethylhexyl 4-methoxybenzalmalonate; 301 2 8 1 1 22. triazine derivatives, such as for example 2,4,6-trianilino (p-carbo-2'-ethyl-r-hexyloxy) -1,3,5-triazine and octyltriazone or dioctylbutamidotriazone (Uvasorb® HEG ); . propane-1,3-diones, such as, for example, 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione; . cetotricyclo derivatives (5.2.1.0) decane. The appropriate water-soluble substances are: 2-phenylbenzimidazol-5-sulfonic acid and the alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium and glucammonium salts thereof; . benzophenone sulfonic acid derivatives, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts; . 3-benzylidenecamphor sulfonic acid derivatives, such as, for example, 4- (2-oxo-3-bornylidenemethyl) benzenesulfonic acid and 2-methyl-5- (2-oxo-3-bornylidene) acid; sulfonic acid and salts thereof. Suitable typical UV-A filters are, in particular, benzoylmethane derivatives, such as, for example, 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione, 4- tert-butyl-4'-methoxydibenzoylmethane (Parsol® 1789), 1-phenyl-3- (4'-isopropylphenyl) -propane-1,3-dione, and enamine compounds. The UV-A and UV-B filters can of course also be used as a mixture. Particularly favorable combinations are benzoylmethane derivatives, for example 4-tert-butyl-4'-methoxydibenzoylmethane (Parsol® 1789) and 2-ethylhexyl-2-cyano-3,3-phenylcinnamate (octocrylene) in combination with cinnamic acid esters, preferably 2-ethylhexyl 4-methoxycinnamate and / or propyl 4-methoxycinnamate and / or isoamyl 4-methoxycinnamate. Such combinations are advantageously combined with water-soluble filters, such as, for example, 2-phenylbenzimidazol-5-sulfonic acid and their alkali metal, alkaline earth metal, ammonium, alkylammonium salts, alkanolammonium and glucammonium.

Said soluble substances, insoluble light-protecting pigments, precisely oxides or finely dispersed metal salts, are also suitable for this purpose. Examples of suitable metal oxides are, in particular, zinc oxide and titanium dioxide and also oxides of iron, zirconium, silicon, manganese, aluminum and cerium, and mixtures thereof. this. The salts that can be used are silicates (steatite), barium sulfate or zinc stearate. Oxides and salts are used in the form of pigments for skin care and protective skin emulsions and decorative cosmetics. The particles must here have a mean diameter of less than 100 nm, preferably 5 to 50 nm and in particular 15 to 30 nm. They may have a spherical shape but it is also possible to use particles that have an ellipsoidal shape or a shape deviating in a manner different from the spherical shape. The pigments can also be surface-treated, that is to say rendered hydrophilic or hydrophobic. Typical examples are coated titanium dioxides, such as for example titanium dioxide T805 (Degussa) or Eusolex® T2000 (Merck). Suitable hydrophobic coating agents are here mainly silicones and, specifically in this case, trialkoxy octylsilanes or simethicones. It is preferred to use micro-nano-pigments so called in sunscreens. It is preferred to use micronized zinc oxide. Biogenic Active Ingredients and Antioxidants The biogenic active ingredients are understood to include, for example, tocopherol, tocopherol acetate, tocopherol palmitate, ascorbic acid, (deoxy) ribonucleic acid, and fragmentation products. these, 13-glucans, retinol, bisabolol, allantoin, phytantriol, panthenol, AHA acids, mino-acids, ceramides, pseudoceramides, essential oils, plant extracts, such as, for example, prunus extract, bambara nut extract and vitamin complexes. Antioxidants interrupt the photochemical reaction chain that is triggered when UV radiation enters the skin. Typical examples thereof are carotenoids, carotenes (e.g., α-carotene,--carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, acid lipoic acid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (e.g., thioredoxin, glutathione, cysteine, cystine, cystamine and glycosyl esters, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl thereof) and salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate , thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts), and sulfoximine compounds (eg buthionine sulfoximine, homocysteine sulfoximine, buthionine sulfone, penta, hexa - , heptathionine sulfoximine) in very low tolerated doses (eg pmol to pmol / kg), and also chelating agents (metal) (eg, α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxyacids (eg citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturated fatty acids and the like. derivatives thereof (for example γ-linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiquinol and derivatives thereof, vitamin C and derivatives (e.g. ascorbyl palmitate, ascorbyl Mg phosphate, ascorbyl acetate), tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (vitamin A palmitate), and benzoyl coniferyl benzoate, ricic acid and derivatives of it, α-glycosylrutin, ferric acid, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiacic acid, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof. thereof, mannose and derivatives thereof, superoxide dismutase, zinc and derivatives thereof (e.g. ZnO, ZnSO4), selenium and derivatives thereof (e.g. selenomethionine), stilbenes and derivatives thereof (for example stilbene oxide, trans-stilbene oxide) and derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of said active ingredients which are according to the invention. Deodorants and antimicrobial agents Cosmetic deodorants act against, mask or eliminate body odor. Body odor results from the effect of skin bacteria on apocrine sweat, with the formation of degradation products that have an unpleasant odor. Deodorants therefore include active ingredients that act as antimicrobial agents, enzyme inhibitors, odor absorbers, or odor masks. . Antimicrobial agents Suitable antimicrobial agents are in principle all substances effective against gram-positive bacteria, such as, for example, 4-hydroxybenzoic acid and its salts and esters, N- (4-chlorophenyl) -N '- ( 3,4-dichlorophenyl) urea, 2,4,4'-trichloro-2'-hydroxydiphenyl ether (triclosan), 4-chloro-3,5-dimethylphenol, 2,2'-methylenebis (6-bromo-4) chlorophenol), 3-methyl-4- (1-methylethyl) phenol, 2-benzyl-4-chlorophenol, 3- (4-chlorophenoxy) -1,2-propanediol, 3-iodo butylcarbamate 2-propynyl, chlorhexidine, 3,4,4'-trichlorocarbanilide (TTC), antibacterial fragrances, thymol, thyme oil, eugenol, clove oil, menthol, mint oil, farnesol, phenoxyethanol, glycerol monocaprate, glycerol monocaprylate, glycerol monolaurate (GML), diglycerol monocaprate (DMC), N-alkylamides of salicylic acid, such as by example the N- octylsalicylamide or N-decylsalicylamide. . Enzyme Inhibitors Suitable enzyme inhibitors are, for example, esterase inhibitors. These are preferably trialkyl citrates, such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate and especially triethyl citrate (Hydagen® CAT). Substances inhibit enzyme activity, thereby reducing odor formation. Other substances which are suitable esterase inhibitors are sulfates or phosphates of sterols, such as, for example, lanosterol sulfate or phosphate, cholesterol, campesterol, stigmasterol and sitosterol, dicarboxylic acids and esters thereof. Examples of these are glutaric acid, monoethyl glutarate, diethyl glutarate, adipic acid, monoethyl adipate, diethyl adipate, malonic acid and diethyl malonate. hydroxycarboxylic acids and esters thereof, such as for example citric acid, malic acid, tartaric acid or diethyl tartrate, and zinc glycinate. . Odor Absorbers Suitable odor absorbers are substances which are capable of absorbing and largely retaining odor-forming compounds. They lower the partial pressure of the individual constituents, thus also reducing their diffusion rate. It is important that in this process the perfumes can remain intact. Odor absorbers are not effective against bacteria. They comprise, for example, as the main constituent, a complex zinc salt of ricinoleic acid or specific fragrances largely neutral in odor which are known to those skilled in the art as "fixatives", such as, for example, extracts of labdanum or styrax or certain abietic acid derivatives. Odor masking agents are perfumes or scented oils which, in addition to their odor masking function, provide the deodorants with their respective fragrance notes. The fragrant oils that may be mentioned are, for example, mixtures of natural and synthetic fragrances. Natural perfumes are extracts of flowers, stems and leaves, fruits, skins, roots, woods, herbs and herbs, needles and branches, and resins and seeds. balms. Animal raw materials, such as, for example, civet and castoreum, are also suitable. Typical synthetic perfume compounds are products of the ester, ether, aldehyde, ketone, alcohol and hydrocarbon type. The ester perfume compounds are, for example, benzyl acetate, p-tert-butylcyclohexyl acetate, linalyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, allyl cyclohexylpropionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether, and the aldehydes include, for example, linear alkanals of 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamenaldehyde, hydroxycitronellal, lilial and bourgéonal, ketones include, for example, ionones and methylcedrylketone, the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol, and the hydrocarbons include mainly terpenes. and balms.

However, it is preferred to use mixtures of different flavors which together produce a pleasant scent. Essential oils of relatively low volatility, which are most often used as aromatic constituents, are also suitable as scented oils, for example sage oil, chamomile oil, clove oil, oil of lemon balm, mint oil, cinnamon leaf oil, linden blossom oil, juniper berry oil, vetiver oil, oligobanum oil, galbanum, labdanum oil and lavandin oil. It is preferred to use bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, a-hexylcinnamaldehyde, geraniol, benzylacetone, cyclamenaldehyde, linalool, strong wood, ambroxan, indole, hedione, sandelice, lemon oil, tangerine oil, orange oil, allylamine glycolate, cyclovertal, lavandin oil, oil sclaree, 13-damascone, bourbon geranium oil, cyclohexyl salicylate, Vertofix heart, iso-E-super, Fixolide NP, evernyl, iraldine gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romilate, irotyl and floramate alone or in mixtures.

Antiperspirants Antiperspirants reduce the formation of perspiration by influencing the activity of the eccrine sudoparous glands, thus acting against underarm moisture and body odor. Aqueous or anhydrous formulations of antiperspirants typically include the following ingredients: astringent active ingredients,. constituents of oils,. nonionic emulsifiers,. coemulsifiers,. consistency regulators,. auxiliaries, such as, for example, thickeners or complexing agents and / or non-aqueous solvents, such as, for example, ethanol, propylene glycol and / or glycerol.

Suitable astringent antiperspirant active ingredients are primarily aluminum, zirconium or zinc salts. Such suitable anti-hydrotic active ingredients are, for example, aluminum chloride, aluminum chlorohydrate, aluminum dichloride, aluminum sesquichlorohydrate and complex compounds thereof, for example with 1,2-propylene glycol, aluminum hydroxyallantoinate, aluminum tartrate and chloride, aluminum zirconium trichlorohydrate, aluminum and zirconium tetrachlorohydrate, aluminum zirconium pentachlorohydrate, and complex compounds thereof, for example with amino acids, such as glycine. In addition, conventional oil-soluble and water-soluble auxiliaries may be present in antiperspirants in relatively small amounts. Such oil-soluble auxiliaries may for example be: anti-inflammatory, skin-protecting or scented essential oils, 15. synthetic active ingredients protecting the skin and / or. scented oils soluble in oil. Typical water-soluble additives are, for example, preservatives, water-soluble fragrances, pH regulators, for example buffer mixtures, water-soluble thickeners, for example soluble natural or synthetic polymers. in water, such as, for example, xanthan gum, hydroxyethylcellulose, polyvinylpyrrolidone or high molecular weight polyethylene oxides. Film Formulators Conventional film formers are, for example, chitosan, microcrystalline chitosan, quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, acrylic acid series polymers, quaternary cellulose derivatives, and the like. collagen, hyaluronic acid and salts thereof, and similar compounds. Blowing agents The swelling agents for the aqueous phases may be montmorillonites, clay minerals, Pemulen grades, and alkyl-modified Carbopol (Goodrich). Other suitable polymers and blowing agents are given by R. Lochhead in Cosm. Toil. 108, 95 (1993). Insect Repellents Suitable insect repellents are N, N-diethyl-m-toluamide, 1,2-pentanediol or ethyl butylacetylaminopropionate. Self-Tanning Agents and Depigmentation Agents A suitable self-tanning agent is dihydroxyacetone. Suitable tyrosine inhibitors, which avoid the formation of melanin and are used in depigmenting agents, are, for example, arbutin, ferulic acid, kojic acid, coumaric acid and ascorbic acid (vitamin VS). Hydrotope Agents It is also possible, to improve the flow behavior, to use hydrotope agents, such as, for example, ethanol, isopropyl alcohol, or polyols. The polyols which are suitable herein preferably have from 2 to 15 carbon atoms and at least two hydroxyl groups. The polyols may also contain other functional groups, especially amino groups, or may be modified with nitrogen. Typical examples are. glycerol; . alkylene glycols, such as, for example, ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, hexylene glycol, and polyethylene glycols with an average molecular weight of 100 to 1000 daltons; . mixtures of technical grade oligoglycerols with a degree of self-condensation of 1.5 to 10, such as, for example, technical grade diglycerol mixtures with a diglycerol content of 40 to 50% by weight; methylol compounds, such as, for example, trimethylolethane, trimethylolpropane, trimethylolbutane, pentaerythritol and dipentaerythritol; . lower alkylglucosides, in particular those having from 1 to 8 carbon atoms in the alkyl radical, such as for example methylglucoside and butylglucoside; 35. sugar alcohols having 5 to 12 carbon atoms, such as, for example, sorbitol or mannitol; 301 2 8 1 1. sugars having 5 to 12 carbon atoms, such as for example glucose or sucrose; . aminosugars, such as, for example, glucamine; . dialcohols, such as diethanolamine or 2-amino-1,3-propanediol. Preservatives Suitable preservatives are, for example, phenoxyethanol, a formaldehyde solution, parabens, pentanediol or sorbic acid, and the silver complexes known as Surfacins®, and also the other classes of substances listed in Annex 6, Parts A and B of the Cosmetics Directive. Scented oils and aromas Scented oils that can be cited are mixtures of natural and synthetic fragrances. The natural fragrances are extracts of flowers (lilac, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petit grain), fruits (anise seeds, coriander, caraway , juniper), fruit peel (bergamot, lemon, orange), roots (pond reed, angelica, celery, cardamom, costus, iris, calamus), wood (pine wood, sandalwood, guaiac wood) , 20 cedar wood, rosewood), herbs and herbs (tarragon, lemongrass, sage, thyme), needles and branches (spruce, fir, pine, pine), resins and balms (galbanum, elemi, benzoin, myrrh, oligobanum, opoponax). Animal raw materials, such as, for example, civet and castoreum, are also suitable. Typical synthetic fragrance compounds are ester, ether, aldehyde, ketone, alcohol and hydrocarbon products. Ester perfume compounds are, for example, benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate, phenylethyl acetate, lynalyl benzoate, benzyl formate, ethylmethylphenyl glycinate, allyl cyclohexylpropionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzylethyl ether, the aldehydes include, for example, linear alkanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamenaldehyde, hydroxycitronellal, lilial and bourgéonal, and ketones. include, for example, ionones, α-isomethylionone and methylcedrylketone, the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and tertpineol, and hydrocarbons. mainly include terpenes and balms. However, it is preferred to use mixtures of different flavors which together produce a pleasant scent. Essential oils of relatively low volatility, which are most often used as aromatic constituents, are also suitable as scented oils, for example sage oil, chamomile oil, clove oil, oil of lemon balm, mint oil, cinnamon leaf oil, linden blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum, labdanum oil and lavandin oil. It is preferred to use bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, a-hexylcinnamaldehyde, geraniol, benzylacetone, cyclamenaldehyde, linalool, strong wood, ambroxan, indole, hedione, sandelice, lemon oil, tangerine oil, orange oil, allylamine glycolate, cyclovertal, lavandin oil, oil sclarée, P-damascone, bourbon geranium oil, cyclohexyl salicylate, Vertofix coeur, iso-E-super, Fixolide NP, évernyle, iraldéine gamma, phenylacétique acid, geranyl acetate, benzyl acetate, rose oxide, romilate, irotyl and floramate alone or in mixtures. Suitable flavors are, for example, peppermint oil, spearmint oil, anise oil, star anise oil, cumin oil, eucalyptus oil, fennel oil, lemon oil, wintergreen oil, clove oil, menthol and the like. Dyestuffs The dyes that can be used are the substances which are approved and suitable for cosmetic purposes, as summarized, for example, in the publication "Kosmetische Färmbemittel" [Cosmetic dyes] by Farbstoffkommission der Deutschen Forschchungsgemeinschaft [German Research Council Coloring Board] , Verlag Chemie, Weinheim, 1984, pp. 81-106. Examples are cochineal A red (CI 16255), patented blue V (CI42051), indigotin (CI73015), chlorophyllin (CI75810), quinoline yellow (CI 47005), titanium (CI77891), RS indanthrene blue (CI69800) and alizarin (C.I58000). It is also possible for a luminescent dye that luminol is present. These dyes are usually used in concentrations of 0.001 to 0.1% by weight, based on the total mixture. According to another embodiment of the present invention, the composition according to the present invention is a dermatological or pharmaceutical composition comprising at least one oligopeptide as defined above, in particular in a dermatologically or pharmaceutically effective amount, and a dermatologically excipient or carrier. or pharmaceutically acceptable. The term "a pharmaceutically effective amount" as used in the present specification indicates an amount that is sufficient to achieve the effectiveness or activity of the oligopeptide according to the invention.

The pharmaceutically acceptable carrier contained in the pharmaceutical composition of the present invention, which is conventionally used in pharmaceutical formulations, includes but is not limited thereto, lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, potassium phosphate, arginate, gelatin, potassium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methyl hydroxybenzoate propyl hydroxybenzoate, steatite, magnesium stearate, and mineral oils. The pharmaceutical composition according to the present invention may further comprise a lubricant, a humectant, a softener, a flavoring agent, an emulsifier, a suspending agent, and a preservative. Details of suitable pharmaceutically acceptable carriers and formulations can be found in Remington's Pharmaceutical Sciences (19th edition, 1995). The pharmaceutical composition according to the present invention can be formulated according to standard techniques known to those skilled in the art with a carrier and / or a pharmaceutically acceptable carrier as described above, finally providing several forms of a unit dosage form. and a multi-dose form. Non-limiting examples of the formulations include but are not limited thereto, a solution, suspension or emulsion in oil or an aqueous medium, an extract, an elixir, a powder, a granule, a tablet and a capsule and may further comprise a dispersing agent and a stabilizer. The total amount of auxiliary compounds and additives may be from 1 to 50% by weight, preferably from 5 to 40% by weight, based on the total weight of the compositions. The cosmetic and dermatological compositions may be prepared by conventional methods cold or hot; it is preferred to use the phase inversion temperature method.

Uses According to another aspect, the subject of the invention is the cosmetic use, advantageously topically, of an oligopeptide according to the invention for improving the firmness of the skin and / or the scalp, improving the elasticity of the skin. skin and / or scalp, fight against skin aging by reducing or removing wrinkles and / or fine lines, improve the hydration of the skin and / or scalp, provide a calming effect soothing to the skin and / or to the skin. scalp or to reduce or treat hair loss, especially to stimulate regeneration or hair growth.

According to a preferred embodiment of the present invention, the improvement of the skin conditions by the oligopeptide according to the present invention or a cosmetic composition comprising at least one such oligopeptide, is the improvement of wrinkles, the improvement of the elasticity of the skin and / or scalp, improving the firmness of the skin and / or the scalp, improving the roughness of the skin and / or the scalp, preventing the aging of the skin skin and / or scalp, improving the hydration of the skin and / or scalp, and improving oxidative deterioration in the skin and / or scalp.

Preferably, the cosmetic use according to the invention is applied topically to at least one area of healthy skin and / or healthy scalp, in particular the human body. For the purposes of the present invention, the term "use and / or cosmetic composition" means a use and / or non-pharmaceutical composition, that is to say which is not intended for a therapeutic use and which aims to to improve the aesthetics and / or comfort and that 301 2 8 1 1 34 is performed / applied on a healthy body part, in particular healthy skin and / or healthy scalp. For the purposes of the present invention, the term "healthy skin" or "healthy scalp" means an area of skin or scalp on which the oligopeptide according to the invention is applied and called "non-pathological" by a dermatologist, that is, no infection, disease or skin condition such as candidiasis, impetigo, psoriasis, eczema, acne or dermatitis, or wounds or wounds. For the purposes of the present invention, the term "topical application" of an ingredient, the direct local application and / or the vaporization of the ingredient on the surface of the skin and / or scalp. In the context of the cosmetic use according to the invention, the oligopeptide is preferably present in a cosmetic composition comprising a topically acceptable cosmetic excipient, advantageously as defined above. According to another aspect, the present invention also relates to a cosmetic care process characterized in that it comprises the topical application to at least one skin zone and / or the scalp of an oligopeptide according to the invention for to improve the firmness of the skin and / or the scalp, to improve the elasticity of the skin and / or the scalp, to combat skin aging by reducing or eliminating wrinkles and / or fine lines, to improve the hydration of the skin, skin and / or scalp, provide a soothing calming effect to the skin and / or scalp to reduce or treat hair loss, in particular to stimulate regeneration or growth of the hair. Thus, for the cosmetic use and the cosmetic care method according to the invention, the area of the skin and / or the scalp is preferably chosen from at least the face, neck, décolleté, bust and / or or the hands, and especially the nasolabial folds, and / or the periorbital area, particularly on dark circles and crow's feet and / or the contour of the lips and / or the forehead, the temporal areas of the scalp, the frontal area of the scalp, the parietal area of the scalp, and / or the vertex or vertex of the skull. The oligopeptides according to the invention and a cosmetic composition containing these oligopeptides are particularly useful for their use in the care of the hair, which may be used in particular to reduce hair loss and improve hair growth. , to increase the number of hair in the anagen phase relative to the hair in the telogen phase, to stimulate the regeneration of the hair follicle, to increase the speed of hair growth, to counteract the thinning and the loss of hair resistance , to improve the metabolism of hair, to improve the appearance of the hair and scalp without causing irritation and / or itching, to soothe the skin and scalp, to reduce the feeling of itching, to reduce the formation 10 gray hair and to reduce oxidative deterioration of the hair. According to yet another aspect, the present invention relates to the oligopeptide according to the invention described above for its use as a medicament. The present invention indeed provides a dermatological or pharmaceutical composition for improving the conditions of the skin comprising as active ingredient at least one oligopeptide according to the invention described above. In this preferred embodiment of the present invention, the improvement of skin conditions by the oligopeptide according to the present invention or a pharmaceutical composition comprising at least one such oligopeptide, is the improvement or elimination of scarring. skin and / or scalp, regeneration of the skin and / or scalp. Thus, the present invention relates to an oligopeptide according to the invention as described above for its use, especially topically, to improve the healing of the skin and / or scalp or stimulate the regeneration of the skin and / or or scalp. In this use the oligopeptide according to the invention is preferably present in a dermatological or pharmaceutical composition comprising a topically acceptable dermatological or pharmaceutical excipient.

Preferably, the oligopeptide according to the invention is present in the composition at a concentration of 0.001 to 10 ppm, preferably 0.01 to 1 ppm by weight, relative to the total weight of the dermatological or pharmaceutical composition.

Other objects and advantages of the present invention will become clear from the following detailed description in conjunction with the claims and the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES FIGS. 1a and 1b are graphs showing the effects of the oligopeptide of this invention for stimulating the growth of keratinocytes (a) and fibroblasts (b) compared to the peptide derived from FGF-10 (KR20110032587).

Figure 2 is a graph showing that the oligopeptide of this invention inhibits oxidative stress (H202) -induced cellular apoptosis. Figure 3 is a graph showing that the oligopeptide of this invention facilitates the growth of hair follicles.

Figures 4a and 4b are graphs showing the stability of the oligopeptide of this invention in aqueous solutions under accelerated aging conditions (28 days at 45 ° C, pH 3.0 (a) or pH 8.0 ( b)) compared to the peptide derived from FGF-10. The present invention will now be described in more detail by examples. It is clear to those skilled in the art that these examples intend to be more specifically illustrative and that the scope of the present invention as given in the appended claims is not limited to or by the examples.

EXAMPLES Example 1 Synthesis of oligopeptide 1 (SEQ ID NO: 1) 700 mg of a chlorotrityl chloride resin (CTL resin, Nova Biochem Cat No. 01-64-0021) were introduced into a reactor. to which 10 ml of methylene chloride (MC) was added, followed by stirring for 3 minutes. After removing the solution, 10 ml of dimethylformamide (DMF) was added to the resulting product and then stirred for 3 min after which the solvent was removed. Ten ml of a solution of dichloromethane was added to the reactor followed by 200 mmol of Fmoc-Arg (pbf) -OH (Bachem, Switzerland) and 400 mmol of DIEA (N, N'-diisopropylethylamine), whereupon the mixture was dissolved by stirring and the reaction was then carried out with stirring for 1 h. After washing, methanol and DIEA (2: 1) dissolved in MC were reacted with the resin for 10 min, and the resulting product was then washed using an excess of DCM / DMF (1: 1). After removing the solution, 10 ml of DMF was added to the resulting product and stirred for 3 min after which the solvent was removed. Ten ml of a deprotection solution (piperidine / 20% DMF) was added to the reactor and stirred for 10 min at room temperature, after which the solution was removed. After the addition of the same volume of the deprotection solution, the reaction was carried out for 10 minutes and the solution was removed and then washed successively with twice DMF, MC and DMF to obtain the Arg resin. (pbf) -CTL. Ten ml of DMF, 200 mmol of Fmoc-Val-OH (Bachem, Switzerland), 200 mmol of hydroxybenzotriazole (HoBt) and 200 mmol of (Benzotriazol-1-yloxy) tris (dimethylamino) phosphonium hexafluorophosphate (Bop) were added to a new reactor, then stirred to solubilize. Four hundred mmol of DIEA was added to the reactor and stirred to dissolve all solid contents. The dissolved amino acid solution was introduced into the reactor containing the deprotected resin and the reaction was stirred for 1 h at room temperature. After removing the reaction solution, the resulting product was stirred three times with DMF solution to remove unreacted residues. The reacted resin was removed to evaluate the progress of the reactions by a ninhydrin test. Deprotection was performed using the deprotection solution twice in the same manner as described above to produce a ValArg (pbf) -CTL resin. After sufficiently washing with DMF and MC, the ninhydrin test was conducted and then successive amino acid bindings were performed as described above. On the basis of the amino acid sequence according to the present invention, Fmoc-Gly, Fmoc-Glu (tBu), FmocGln (trt) and Fmoc-Leu were successively attached to the resins. The Fmoc-protecting group was removed by incubating with the deprotection solution twice for 10 min.

For acetylation, acetic anhydride, DIEA and HoBt were incubated with peptidyl resins twice for 1 hour. The peptidyl resin was washed three times with DMF, MC and methanol respectively, then dried under nitrogen, after which it was dried under vacuum under P 2 O 5. The dried resins were reacted with 30 ml of a cleavage solution [containing 95% trifluoroacetic acid (TFA), 2.5% distilled water, 2.5% thioanisole] for 2 h at room temperature. ambient with intermittent stirring. The resin was filtered and washed with a small volume of TFA solution, after which the filtrate was combined with the mother liquor. After distillation under reduced pressure to reduce the total volume by two, precipitation was induced using 50 ml of cold ether and the precipitates formed by centrifugation were collected and then washed twice with cold ether. After removal of the mother liquor, the resulting product was dried under nitrogen to produce oligopeptide 1 NH 2 -Lu-Gln-Glu-Gly-Val-Arg-OH in an amount of 0.7 g (85% yield) and its molecular weight was measured as 700.7 (theoretical MW, 700.7) using a molecular weight analysis device. Example 2 Influence of the Oligopeptide on the Growth of Keratinocytes and Fibroblasts In order to evaluate oligopeptide 1, SRB (sulforhodamine B, Sigma-Aldrich) colorimetric analysis was performed using HaCaT keratinocytes and NIH3T3 fibroblasts. . This assay was performed comparatively with a peptide derived from FGF-10 (synthesized as described in Korean Patent Application KR20110032587 in Synthesis Example 1 (Table 1)). HaCaT keratinocytes and NIH3T3 fibroblasts were cultured in 250 ml flasks containing DMEM (modified Dulbecco's Eagle medium: Gibco, U.S.A) supplemented with 10% FBS (fetal bovine serum, Sigma). The cells were cultured with a 1% trypsin solution and then centrifuged to collect the cell pellets. After resuspension in FBS-free DMEM, the cells were aliquoted (3 x 10 3 cells) in each well of the plates (96 well) and cultured under 5% CO 2 for 24 h at 37 ° C. After a 24 h culture, the medium was modified with a fresh medium containing no serum without (control) or with the oligopeptide to be tested (10 ng / ml and 10 μg / ml) dissolved in water. and 10% DMSO, and the cells were incubated for 72 h under the same conditions as described above. After removing the supernatants, the cells were fixed with ethanol and then washed three times with PBS (phosphate buffered saline). The cells were then incubated with SRB solution and sufficiently washed with 1% acetic acid. Microscopic observation and a measurement of absorbance at 590 nm were performed to verify cell viability. Conclusion Figures 1a and 1b respectively show the growth data of keratinocytes and fibroblasts. As shown in Figures 1a and 1b, oligopeptide 1 of this invention induced growth of keratinocytes and fibroblasts, dependent dose growth. In particular, the oligopeptide 1 according to the present invention has better effects on the growth of keratinocytes and fibroblasts than the peptide derived from FGF-10.

Therefore, the oligopeptide of the present invention has activity on the regeneration of hair, skin and scalp by stimulating the growth of keratinocytes and fibroblasts. Example 3 Influence of Oligopeptide on Apoptosis Inhibition HaCaT keratinocytes (3 × 10 3 cells) were cultured in 96-well plate under 5% CO 2 for 24 h at 37 ° C. After a 24 h culture, the medium was modified with fresh medium containing no serum and 5 μM H 2 O 2 was added to each well to induce apoptosis. The cells were incubated for 72 h under the same conditions as described above in Example 2 without (control) and with the oligopeptide (100 ng / ml or 1 mg / ml) dissolved in water and 10 % of DMSO. After removing the supernatants, the cells were fixed with ethanol and washed three times with PBS (phosphate buffered saline) buffer. The cells were then incubated with SRB colorimetric solution and sufficiently washed with 1% acetic acid. Microscopic observation and a measurement of absorbance at 590 nm were performed to verify cell viability. Conclusion It follows that H202-induced apoptosis of keratinocytes was inhibited by oligopeptide 1 (Figure 2). It can therefore be appreciated that the oligopeptide of the present invention has an effective activity for cellular protection against oxidative damage and cell death.

Example 4 Influence of Oligopeptide on Growth of Hair Follicles Human hair follicles were micro-dissected from skin samples obtained by plastic surgery. Hair follicles were cultured in supplemented William's medium without control (10) or with oligopeptide 1 (1 μg / ml or 10 μg / ml). For each condition, 10 follicles were treated. The lengthening of the body of the hair was measured for each hair follicle after 10 days of incubation. Figure 3 presents growth data for hair follicles.

Conclusion As shown in Figure 3, it will be appreciated that oligopeptide 1 stimulates hair follicle growth in comparison with control, as a function of dose (p <0.05). It will therefore be appreciated that the oligopeptide of the present invention has an activity effective on hair growth. Example 5 Influence of oligopeptide on the modulation of expression of VCAN, BDNF, MGED1, BIRC5 and MMP9 in hair follicles Human hair follicles were micro-dissected from skin samples obtained by plastic surgery . Hair follicles were cultured in supplemented William's medium without (untreated state, control) or with oligopeptide 1 at 10 μg / ml. 10 follicles were treated for each condition. After 72 h of culture, the total RNA contained in the hair follicle was extracted. Quantitative measurement and RNA quality control were performed using an Agilent bioassay device. After amplification and labeling, the total RNAs were hybridized on a DNA chip to analyze the expression profile of the genes. Each variation of gene expression was evaluated and expressed per 100 for the untreated (control) state.

Hair follicle treatment with oligopeptide 1 modulated the expression of the VCAN, BDNF, BIRC5, and MMP9 genes (Table 1). Symbol Gene name Modulation of Gene Gene Expression by Oligopeptide 1 vs. Versican 178 VCAN Control or "Chondroitin Sulfate Proteoglycan 2" BDNF "Brain-Derived Neurotrophic 61 Factor or Neurotrophin MAGED1" Melanoma Antigen Family 45 or NRAGE D1 "or" Neurotrophin Receptor-Interacting Mage Homolog "BIRC5" Baculoviral IAP Repeat 164 Containing 5 "or Survivin MMP9" Matrix Metallo Peptidase 9 "601 or Gelatinase B Table 1: Modulation of VCAN, BDNF, BIRC5, MAGED1 Gene Expression The values are expressed in comparison with 100 for the control (untreated state) The expression of the VCAN gene, encoding the Versican proteoglycan, was induced by oligopeptide 1. The VCAN gene is strongly expressed in fibroblasts of dermal papillae, anagen follicles and its expression is decreased in the catagen phase This observation illustrates the involvement of the VCAN gene in the stimulation of hair growth Versican protein is also present in the skin, mainly in the epidermal proliferation layer and in the extracellular matrix (ECM) dermal associated with the elastic network. The VCAN gene regulates the adhesion and proliferation of cells, elastic fibrillogenesis and the interactions between the different constituents of the extracellular matrix. It is also involved in the proper hydration of the extracellular matrix. Stimulation of Versican expression demonstrated in Table 1 can therefore have a beneficial effect on both the quality of the skin and effective hair growth. The expression of the BDNF gene was strongly decreased with the oligopeptide 1. BDNF and its TrkB receptor are expressed by the keratinocytes of the internal epithelial sheath (IRS) and of the external epithelial sheath (ORS) in the late anagen phase. BDNF inhibits the lengthening of the body of the hair, induces a premature catagen development and inhibits the proliferation of keratinocytes. The BDNF gene is further expressed by keratinocytes, fibroblasts or mast cells. BDNF has been identified as having a fundamental role in atopic dermatitis or allergic inflammation. Its expression is also greatly increased in the phenomenon of itchy skin. The decrease of the expression of BDNF by the oligopeptide 1 can therefore stimulate the growth of the hair and limit the itching and inflammation of the skin. The expression of the MAGED1 gene also strongly decreased with oligopeptide 1. The NRAGE protein interacts with the generic neurotrophin p75NTR receptor (or NGFR) and participates in the signal induced by neurotrophins bound to this receptor (such as BDNF). MAGED1 is coexpressed with p75NTR, the signaling of which induces an involution of the hair follicle characteristic of the catagen phase. MAGED1 is specifically expressed in ORS keratinocytes at the end of the anagen phase and its inactivation delays the catagen phase. MAGED1 is thus an adapter protein that binds the p75NTR receptor signaling the apoptosis of ORS cells in order to limit the anagen phase and induce the catagenic phase of the hair follicles. In the skin, p75NTR is expressed in more differentiated transient amplification cells and may be involved in mast cell activation during allergic and non-allergic inflammation. Oligopeptide 1 can, by acting on both BDNF and MAGED1, modify the neurotrophin signaling pathway to increase hair growth and limit inflammation of the skin. Table 1 shows that BIRC5 gene expression was also stimulated by oligopeptide 1. BIRC5 exhibits both proliferative and anti-apoptotic activities on different cell types. In the anagenous hair follicle, BIRC5 is strongly expressed in the keratinocytes of MEC and ORS, whereas its expression decreases strongly in the catagenic hair follicle. This observation suggests that BIRC5 is involved in maintaining growth of the hair follicle by stimulating proliferation and protecting cells from apoptosis. In addition, BIRC5 is highly expressed in endothelial cells of a superficial region of alopecia after treatment with diphencyprone, suggesting its involvement in the regeneration of new hair follicles. Oligopeptide 1 can therefore, by stimulated expression of BIRC5, improve hair growth and participate in the health of the skin of the adult. Finally, Table 1 shows that MMP9 gene expression is induced by oligopeptide 1. Gelatinase proteases (MMP-2 and MMP-9) are the only matrix metalloproteinases expressed in hair follicles. MMP-9 has recently been identified as a major proteinase involved in the remodeling of MEC induced during hair channel formation. During the hair growth cycle, the hair channel is strongly modified with an alteration of the morphology of the hair follicle. MMP-9 seems to play a key role in this evolution and 25 in the neo-formation of the hair channel. Oligopeptide 1 can, by stimulating the expression of the MMP-9 gene, increase the neoformation of the hair channel in areas of alopecia. Example 6: Stability of oligopeptide under accelerated aging conditions Oligopeptide 1 and FGF-10 derived peptide (as described in KR20110032587) were dissolved at a concentration of 0.11 mg / ml in an aqueous solution at pH 3.0 and 8.0. The prepared solutions (1 ml) were introduced into glass vials and allowed to stand under accelerated aging conditions at 45 ° C.

The solutions at pH 3.0 and pH 8.0 were then taken at days 0, 7, 15, 21 and 28, and the respective contents of oligopeptide 1 and peptide derived from FGF were then quantified. -10 by high pressure liquid chromatography (HPLC) (respectively Figures 4a and 4b).

Conclusion As a result, it has been demonstrated that the oligopeptide of the present invention is stable after 28 days under accelerated aging conditions while the FGF-10 related peptide is strongly degraded under the same conditions (Fig. 4a). and Fig. 4b).

Example 7: Preparation of Oligopeptide Liposomal Solution 50 mg of the peptide synthesized in Example 1 was dissolved in 500 ml of distilled water. The peptide solution was mixed with 5 g of lecithin, 0.3 ml of sodium oleate, 50 ml of ethanol and 2 g of soybean oil, and its volume was adjusted to 1 liter with water. 'distilled water. The resulting solution was subjected to a microfluidizer for emulsification, allowing liposomes to be obtained. Example 8: Cosmetic formulations Skin emulsion Ingredient% by weight Water Qs 100 Glyceryl (and) ceteareth-20 (and) (and) 6.00 ceteareth-12 (and) cetearyl alcohol cetyl palmitate Cetearyl alcohol 2, 50 Ethylhexyl palmitate 6.00 Hexyldecanol (and) hexyldecyl laurate 5.00 Caprylic / capric triglyceride 3.00 Di methicone 1.00 Xanthan gum 0.20 Chlorphenesin (and) methylparaben 0.40 Glycerin 4.00 Carbomer 15 , 00 Oligopeptide 0.01 301 2 8 1 1 45 Hair lotion Ingredient% by weight Water Qs 100 Chlorphenesin (and) Methylparaben 0.30 Xanthan gum 0.10 Alcohol 10.00 Oligopeptide 0.003 Shower gel for skin and skin hair Ingredient% by weight Water Qsp 100 Sodium coco-sulfate 10.80 Coco-glucoside 19.30 Coco-glucoside (and) glyceryl oleate 3.00 Sodium benzoate 0.50 Cyperus oil Esculentus 0.10 Citric acid 0 , 70 Laurylglucoside (and) stearyl citrate 4.00 Sodium chloride 0.30 Citric acid 0.10 Oligopeptide 0.005 5 10 301 2 8 1 1 46 Shampoo Ingredient% by weight Water Qs 100 Polyquaterniu m-7 1.00 Sodium laureth sulfate 30.00 Coco-glucoside 4.00 Coca midopropyl betaine 6.00 Citric acid 0.70 Sodium Chloride 1.00 Trioleate PEG / PPG-120/10 0.50 tri methylol propane, u reth-2 Chloromethylisothiazolinone, methylisothiazolinone 0.05 Oligopeptide 0.001 Pearlescent shampoo Ingredient% by weight Water Qsp 100 Polyquaterniu m -11 1.00 Sodium laureth sulfate 30.00 U reth-2 1.00 Coco-glucoside 4.00 Cocamidopropyl betaine 6.00 Glycol distearate, laureth-4, 4.84 cocamidopropyl betaine Citric acid 0, 70 Sodium chloride 1.84 Chloromethylisothiazolinone, methylisothiazolinone 0.05 Oligopeptide 0.0005 301 2 8 1 1 47 Gasoline Ingredient% by weight Water Qs 100 Glycerine 10.00 1,3-butylene glycol 5.00 PEG 1500 2.00 Allantdine 0.10 DL-Panthenol 0.30 Hydroxyethylcellulose 0.10 Sodium Hyaluronate 8.00 Carboxyvinyl Polymer 0.20 Tri ethanola mine 0.18 Octyldodeceth-16 0.40 Ethanol 6.00 Chlorphenesin (and) methylparaben 0.30 Oligopeptide 0.001

Claims (4)

REVENDICATIONS1. Oligopeptide of formula (I) - Y - R2, wherein: Y is a peptide of sequence SEQ ID NO: 1 R1 is linked to the terminal NH2 group of said peptide and selected from the group consisting of: 1-1 - an alkyl group carbonyl, alkenylcarbonyl or alkynylcarbonyl, linear or branched having 1 to 24 carbon atoms, which is functionalized with a -OH, -SH, -COOH or -CONH2 -R2 group is the terminal carboxylic group of said peptide, that is -COOR3 or -CO-NH2, and wherein R3 is selected from the group consisting of: H - a linear or branched alkyl, alkenyl or alkynyl group having 1 to 24 carbon atoms, which is functionalized with a -OH, -SH group, - COOH or -CONH2. 2 - Oligopeptide of formula (I) according to claim 1, wherein R1 is -H and / or R2 is -COOH. 3 - Cosmetic, dermatological or pharmaceutical composition comprising at least one oligopeptide as defined in claims 1 or 2 and a cosmetically, dermatologically or pharmaceutically acceptable excipient respectively, preferably topically acceptable. 4 - Composition according to claim 3, characterized in that the oligopeptide is present in the cosmetic composition at a concentration of 0.001 to 10,000 ppm, preferably from 0.01 to 1000 ppm. - Composition according to claim 3 or claim 4, characterized in that it also contains one or more auxiliary compounds or additives. 6 - Composition according to any one of claims 3 to 5, characterized in that the oligopeptide is present in a solubilized form in liposomes. 7 - Cosmetic use, advantageously topically, of an oligopeptide as defined in claims 1 or 2 to improve the firmness of the skin and / or the scalp, improve the elasticity of the skin and / or scalp , fight against skin aging by reducing or eliminating wrinkles and / or fine lines, improving the hydration of the skin and / or the scalp or reducing or treating hair loss, in particular to stimulate the regeneration or growth of the hair . 8 - Cosmetic use according to claim 7, characterized in that the oligopeptide is applied topically to the healthy skin and / or the healthy scalp, in particular the human body. 9 - cosmetic use according to claim 7 and claim 8, characterized in that the oligopeptide is applied to at least one skin area and / or scalp selected from at least the face, neck, décolleté, bust and / or the hands, and especially the nasolabial folds, and / or the periorbital area, especially on dark circles and crow's feet and / or the contour of the lips and / or the forehead, the temporal areas of the scalp , the frontal area of the scalp, the parietal area of the scalp, and / or the vertex or vertex of the skull. 10 - Cosmetic use according to any one of claims 7 to 9, characterized in that the oligopeptide is present in a cosmetic composition comprising a topically acceptable cosmetic excipient, advantageously as defined in claims 3 to 6. 11 - Care process cosmetic composition, characterized in that it comprises the topical application to at least one skin zone and / or the scalp of an oligopeptide as defined in claims 1 or 2 to improve the firmness of the skin and / or scalp, improve the elasticity of the skin and / or the scalp, fight against skin aging by decreasing or removing wrinkles and / or fine lines, amertordr 15-05-14 3 0 12 8 1 1 3 FR1360835 hydration of the skin and / or scalp or to reduce or treat hair loss, especially to stimulate regeneration or growth of hair. 12 - Cosmetic treatment method according to claim 11, characterized in that the skin area and / or the scalp is chosen from at least the face, neck, décolleté, bust and / or hands, and especially the nasolabial folds, and / or the periorbital zone, in particular on dark circles and crow's feet and / or the contour of the lips and / or the forehead, the temporal zones of the scalp, the frontal zone of the scalp, the parietal area of the scalp, and / or the vertex or top of the skull. 13 - Oligopeptide as defined in claims 1 or 2 for use as a medicament. 14 - Oligopeptide as defined in claims 1 or 2 for its use, especially topically, to improve the healing of the skin and / or scalp or stimulate the regeneration of the skin and / or scalp and / or to provide a calming soothing effect to the skin and / or scalp. 15 - Oligopeptide according to claim 14, characterized in that it is present in a dermatological or pharmaceutical composition comprising a topically acceptable dermatological or pharmaceutical excipient. 16 - Oligopeptide according to claim 15, characterized in that it is present in the composition at a concentration of 0.001 to 10 ppm, preferably 0.01 to 1 ppm by weight, relative to the total weight of the dermatological composition or pharmaceutical. 15-0544