FR2940971A1 - New peptides are circadian locomotor output cycles kaput protein activators useful to prevent/treat signs of skin aging, to protect skin against UV radiation, and to prevent or fight against diseases related to oxidation processes - Google Patents

Abstract

Peptides (I), where the sequence of (I) comprises 5-15 amino acid residues, are new. Peptide compounds of formula (R 1-(AA) n-X 1-His-Ser-Gly-Tyr-Glu-X 2-(AA) p-R 2) (I), where: the sequence of (I) comprises 5-15 amino acid residues, the substitutions of amino acids X 1and X 2are substituted by other chemically equivalent amino acids, are new. X 1valine, isoleucine or absent; X 2alanine, proline or absent; AA : amino acid or its derivative; n, p : 0-4; R 1primary amine function of N-terminal amino acid (optionally substituted by a protecting group comprising acetyl group, benzoyl group, tosyl group or benzyloxycarbonyl group); R 2hydroxyl group of the carboxyl function of C-terminal amino acid (optionally substituted by protecting group comprising 1-20C alkyl, NH 2, NHY 1, NY 1Y 1); and Y 11-4C alkyl. Independent claims are included for: (1) a cosmetic composition comprising (I); and (2) a cosmetic treatment method comprising topically applying the composition on the skin or keratinous appendage to prevent or treat signs of skin aging or protect the skin against UV radiation. ACTIVITY : Dermatological. MECHANISM OF ACTION : Circadian locomotor output cycles kaput (clock) protein activator. The ability of (I) to activate clock protein was tested in fibroblast cell culture using Western blot study. The result showed that the increased percentage of clock protein in fibroblast cells was 100% (for control treated cell) and 133% (for SEQ ID NO: 3 treated cell).

Description

The present invention relates to peptide compounds of general formula (I) R1- (AA) nX-His-Si-Gly-Tyr-Glu-X2-(AA) p -R2 as well as their uses in cosmetics and / or pharmaceuticals in order to prevent and correct the effects of aging and UV aggressions of the skin and skin appendages.

The primary function of the epidermis is to provide a barrier between the external environment and the internal environment. It is the outermost layer of the epidermis, the stratum corneum, which provides this function. It is composed of keratinocytes at the final stage of their differentiation, the corneocytes, sealed to each other by a thick intercellular cement, both flexible and impermeable. This physical barrier of the skin allows the human body to protect itself from many types of aggression. These attacks can have various intrinsic origins, such as chronological aging or biochemical changes that occur during states of fatigue, stress, hormonal changes such as during pregnancy .... Other attacks they have an extrinsic origin such as pollution, sun, diseases .... In response to these aggressions, the appearance of the skin is modified and we see appearing then wrinkles and fine lines, tasks hyper or d hypopigmentation, dryness or dehydration of the skin, thinning of the epidermis, elastosis, imperfections, age spots ... These changes are due to the alteration of cell renewal functions. cellular cohesion, synthesis of collagen, elastin and other proteins and ultimately lead to a decrease in the protective barrier qualities of the skin and an unsightly appearance thereof. All these changes affect not only the skin, but also the integuments such as nails and hair. For example, the hair becomes dull, or graying, or falls early ...

In order to overcome these disadvantages, many cosmetic compositions have been proposed in recent years. These compositions included the use, alone or in combination, of moisturizing, soothing, anti-inflammatory, anti-free radical, anti-seborrhoeic, cicatrizing, lightening, keratolytic agents. However, none of these compositions allows the nowadays, to prevent or correct the effects of intrinsic or extrinsic aging of the skin.

Surprisingly, we have found that peptide compounds of the following general formula R1- (AA) n-X1-His-Sier-Gly-Tyr-Glu-X2-(AA) p R2. It had an anti-aging effect on the skin by a global action on various characteristic symptoms of the latter. No document of the prior art describes such peptide compounds in order to obtain an anti-aging effect. In addition, these peptide compounds are characterized by being Clock gene activating agents involved in the regulation of the circadian cycle. Therefore, the subject of the present invention is Clock Activating Peptide (PAT) peptides and their use in cosmetic and pharmaceutical compositions to prevent or correct signs due to aging and UV aggressions of the skin and dander. The circadian clock is controlled by a negative regulatory loop involving a set of genes, including the genes Per-1 (Period), Clock and BMAL-1 (Brain and Muscle tRNA-like Protein). Aging has been shown to be accompanied by a change in biological rhythms, with a decrease in amplitude and a tendency to phase advance (Weinert D., Chronobiol., 2000, 17: 261). 83). In addition, it has been shown that the circadian clock was altered by this same aging. Heretofore, in the prior art, numerous applications have already been proposed for the use of nucleotides and / or proteins derived from the Clock, Per-1 or BMAL-1 genes. For example, US Pat. No. 6,291,429 describes the use of the Clock gene product for the resynchronization of the sleep cycle or of physiological or endocrine processes, the resynchronization of the body after a jet lag. Prior art document discloses the use of specific peptides activating Clock to prevent or correct the signs of aging or the consequences of UV aggressions.

The present invention firstly provides peptide compounds of the following formula (I): ## STR1 ## wherein equal to zero, X2 represents an alanine, a proline, or is zero, AA represents any amino acid, or a derivative thereof, and n and p are integers between 0 and 4, 2940971 -4-RI represents the primary amino function of the N-terminal amino acid, free or substituted with a protecting group that may be selected from an acetyl group, a benzoyl group, a tosyl group or a benzyloxycarbonyl group, R2 represents the hydroxyl group of the functional group; carboxyl of the C-terminal amino acid, free or substituted by a protecting group which may be chosen from a C 1 -C 20 alkyl chain, or an NH 2, NHY or NYY group with Y representing a C 1 to C 4 alkyl chain, said sequence of fo general formula (I) consisting of 5 to 15 amino acid residues, said sequence of general formula (I) may comprise substitutions of amino acids XI and X2 by other chemically equivalent amino acids.

The second subject of the present invention is a cosmetic or dermopharmaceutical composition comprising peptide compounds of general formula (I).

The third subject of the present invention is the use of a cosmetic or dermopharmaceutical composition comprising peptide compounds of general formula (I). Finally, the fourth subject of the present invention is a method of cosmetic treatment using a composition comprising peptide compounds of general formula (I).

The first subject of the invention relates to a peptide compound of the following general formula (I): ## STR5 ## wherein R 1 - (AA) 2 -Xi-His-Si-Gly-tyr-Glu-x-2 (AA) p - valine, an isoleucine or is zero, X2 represents an alanine, a proline, or is zero, AA represents any amino acid, or a derivative thereof, and n and p are integers between 0 and 4, RI represents the primary amine function of the N-terminal amino acid, free or substituted with a protecting group which may be selected from an acetyl group, a benzoyl group, a tosyl group or a benzyloxycarbonyl group, R 2 represents the hydroxyl group of the carboxyl function of the C-terminal amino acid, free or substituted by a protecting group which may be selected from an alkyl chain of C 1 to C 20, or an NH 2, NHY or NYY group with Y representing a C1 to C4 alkyl chain, said sequence of general formula (I) consisting of 5 to 15 amino acid residues, said sequence of general formula (I) possibly comprising substitutions of amino acids XI and X2 by other chemically equivalent amino acids. Preferably, said peptide is a peptide whose number of amino acids is between 5 and 15.

The peptide compound according to the invention is characterized in that it is used as an activating active ingredient of Clock. Clock activator peptide is understood to mean any peptide or biologically active derivative capable of increasing the activity of Clock. either by increasing the protein synthesis of Clock (by direct or indirect modulation of the Clock gene expression) or by other biological processes such as the stabilization of the Clock protein or the stabilization of the messenger RNA transcripts.

Preferably, the peptide compound has at least one functional group protected by a protective group, this protective group being either an acylation or an acetylation of the amino-terminal end, or an al-nidation or esterification of the end-member. carboxy-terminal, both.

Preferably, the peptide compound has one of the following sequences: (SEQ ID NO: 1) Ile-HisSer -GlyTyr -Glu -NH2 (SEQ ID No. 2) Arg -Val-His-SerGly -Tyr -Glu -Ala -Arg (SEQ ID No. # 3 His ûSer ûGly ûTyr ûGlu -NH2 (SEQ ID No. 4) Gin ûLeu - His ûSer ûGly ûTyr ûGlu ûPro -NH2 (SEQ ID No. 5) Ile ûArg - His ûSer ûGly ûTyr ûGlu ûPro (SEQ ID No. 6 In a particular embodiment, the sequence of the peptide compound is the sequence SEQ ID No. 2, that is to say Arg ΔVal-His ûSer ûGly ûTyr ûGlu ûAla - ΔGly ûGly ûTyr ûGlu ûAla ûPro Arg. In another embodiment, the sequence of the peptide compound is the sequence SEQ ID No. 3), that is to say His ûSer ûGly ûTyr ûGlu -NH2. The invention also relates to homologous forms of these sequences. The term "homologous" denotes, according to the invention, any peptide sequence identical to at least 50%, or preferably at least 80%, and even more preferentially to at least 90% of said peptide sequence, chosen from the sequences SEQ ID No. 1 to SEQ ID No. 6. The peptide sequence identical to at least X% is intended to designate a percentage identity between the amino acid residues of the two sequences to be compared, obtained after the optimal alignment of the two sequences. Optimal alignment is achieved using local homology algorithms such as those used by BLAST P or T BLAST N computer software available on the NCBI site. The term homologous may also refer to a peptide which differs from the sequence of a peptide of SEQ ID NO: 1 to SEQ ID NO: 6 by the substitution of chemically equivalent amino acids, i.e. substitution of one residue for another with the same characteristics. Thus, the classical substitutions are between Ala, Val, Leu and Ile; between Ser and Thr; between the acid residues Asp and Glu: 20 between Asn and Gln and between the basic residues Lys and Arg; or between the aromatic residues Phe and Tyr.

The term peptide denotes a sequence of two or more amino acids linked to each other by peptide bonds or by modified peptide bonds. By peptide is meant the natural or synthetic peptide of the invention as described above, or at least one of its fragments, whether obtained by proteolysis or synthetically, or any natural peptide. or synthetic whose sequence is totally or partially constituted by the sequence of the previously described peptide. In order to improve the resistance to degradation, it may be necessary to use a protected form of the peptide according to the invention. The form of protection must obviously be a biologically compatible form and must be compatible with use in the field of cosmetics or pharmacy. Many biologically compatible forms of protection can be envisaged. They are well known to those skilled in the art as. for example, acylation or acetylation of the amino-terminus, or amidation or esterification of the carboxy-terminus. Thus, the invention relates to a composition as defined above, characterized in that the peptide of sequence SEQ ID No. 1 to SEQ ID No. 6 is in protected form or not. Protection based on a substitution on the amino-terminus by an acetyl group, a benzoyl group, a tosyl group or a benzyloxycarbonyl group can be used. Preferably, protection is used based on the amidation of the hydroxyl function of the carboxy-terminal end by a NYY group with Y representing a C 1 to C 4 alkyl chain, or esterification with an alkyl group. It is also possible to protect both ends of the peptide.

The peptide of general formula (I) according to the invention can be obtained either by conventional chemical synthesis (in solid phase or in homogeneous liquid phase) or by enzymatic synthesis (Kullman et al., J. Biol Chem 1980, 225, 8234). from constituent amino acids or their derivatives. The peptide according to the invention may be of natural or synthetic origin. Preferably according to the invention, the peptide is obtained by chemical synthesis. Finally, the active ingredient may be a single peptide, a mixture of peptides or peptide derivatives and / or consisting of amino acid derivatives.

The peptide compound according to the invention can be used as a medicament.

The second subject of the present invention relates to cosmetic compositions comprising said peptide compound of general formula (I). Preferably, the compositions according to the invention are in a form suitable for topical application comprising a cosmetically or dermatologically acceptable medium. Cosmetically or dermatologically acceptable means media suitable for use in contact with human skin or integuments, without risk of toxicity, incompatibility, instability, allergic response and the like. Preferably, said peptide compound is present in the composition at a concentration of between about 0.0005 and 500 ppm, and preferably at a concentration of between 0.01 and 5 ppm. In the compositions according to the invention, the peptide compound is first solubilized in one or more cosmetically or dermatologically acceptable solvents, such as water, glycerol, ethanol, propylene glycol, butylene glycol or dipropylene. glycol, ethoxylated or propoxylated diglycols, cyclic polyols, petroleum jelly, a vegetable oil or any mixture of these solvents. According to yet another advantageous embodiment, the active principle according to the invention is solubilized beforehand in a cosmetic or pharmaceutical vector such as liposomes or adsorbed on organic powdery polymers, mineral supports such as talcs and bentonites, and more generally solubilized. in, or attached to, any physiologically acceptable vector. The compositions for application to the skin may be in the form of aqueous or hydroalcoholic solution, water-in-oil or oil-in-water emulsion, microemulsion, aqueous or anhydrous gel, serum, or dispersion. vesicles, patch, cream, spray, ointment, ointment. lotions, colloid, solution, suspension or other. The compositions may also be applied to the integuments in the form of shampoo, dye or mascara to be applied by brush or comb, in particular on the eyelashes, eyebrows or hair, or care for the nails such as the varnish.

In a particular embodiment, the composition according to the invention contains, in addition, at least one other active ingredient promoting the action of said peptide active principle. The following classes of ingredients may be mentioned in a non-limiting manner: other peptide active agents, plant extracts, cicatrizing, anti-aging, anti-wrinkle, soothing, anti-radical and anti-UV agents, agents stimulating the synthesis of dermal macromolecules or energy metabolism, moisturizing, anti-bacterial, anti-fungal, anti-inflammatory, anesthetic agents, modulating agents differentiation, pigmentation or skin depigmentation, stimulating agents the shoot nails or hair .... Preferably, use an anti-radical agent or antioxidant, or an agent stimulating the synthesis of dermal macromolecules, or an agent stimulating the energy metabolism. In addition, additives such as thickeners, emulsifiers, humectants, emollients, fragrances, antioxidants, film formers, chelants, sequestering agents, conditioners, etc. may be added to the composition.

In all cases, those skilled in the art will ensure that these adjuvants and their proportions are chosen in such a way as not to adversely affect the advantageous properties of the composition according to the invention. These adjuvants may, for example. correspond to 0.01 to 20% of the total weight of the composition. When the composition of the invention is an emulsion, the fatty phase may represent from 5 to 80% by weight and preferably from 5 to 50% by weight relative to the total weight of the composition. The emulsifiers and co-emulsifiers used in the composition will be chosen from those conventionally used in the field under consideration. For example, they can be used in a proportion ranging from 0.3 to 30% by weight, relative to the total weight of the composition.

A third object of the present invention relates to the use of a composition according to said invention to prevent or treat skin signs of aging. Cutaneous signs of aging include, but are not limited to, all visible manifestations on the skin caused by aging. In particular, wrinkles, fine lines, cracks, enlarged pores, imperfections, loss of firmness, discoloration, age spots, keratoses, loss of collagen, and other changes in the dermis and epidermis are described. aging also means any changes in the external appearance of the skin and skin appendages due to aging, such as, for example, the superficial roughness of the stratum corneum, wrinkles and fine lines, but also any internal change in the skin that does not does not systematically result in a modified external appearance such as, for example, thinning of the dermis or any other internal degradation of the skin subsequent to exposure to ultraviolet (UV) radiation.

A fourth object of the present invention relates to the use of a composition according to said invention for the protection of the skin against the aggressions due to UV radiation.

Another object of the invention relates to the use of an effective amount of peptide active ingredient according to the invention, for the preparation of a pharmaceutical composition for preventing or combating pathologies related to oxidation processes.

A last subject of the present invention relates to a cosmetic treatment method characterized in that a composition containing an effective amount of peptide active ingredient 2940971 -10- is applied topically to the skin or integuments to be treated to prevent or treat treat the signs of skin aging or protect the skin against UV radiation. Furthermore, this cosmetic treatment method is characterized in that the composition is applied before bedtime to respect the circadian rhythm of the skin to obtain a rejuvenating effect on the skin. Indeed, during the night, the skin favors renewal functions as well as metabolic processes of synthesis. Therefore, the application of the composition as claimed, respecting the biological rhythm of the skin provides a rejuvenating effect, stimulating cell renewal, and regenerating. The following examples describe and demonstrate the effectiveness of peptide compounds as described according to the invention. The cosmetic formulations mentioned are representative of the invention but are given by way of illustration only and should not be interpreted as limitations of the present invention. EXAMPLE 1 Demonstration of the Activating Effect of the Peptide SEQ ID No. 3 on the Expression of the Clock Protein on Fibroblasts in Culture A study of the activating effect of the peptide SEQ ID No. 3 was carried out by evaluating the expression of Clock proteins in western blot on fibroblasts in culture and in immunohistochemistry by labeling the Clock protein by immunolabeling. The technique of western blotting is a semi-quantitative method that allows to assess the level of Clock proteins in dermal cells.

Protocol a) Western blot study Fibroblasts in cultures are cultured in 100 mm diameter dishes at 37 ° C. in a humidified atmosphere containing 5% CO 2 for 16 h in the presence or absence of the peptide SEQ ID No. 3, diluted. 1% (from a 10-4M solution). The cells are rinsed and then detached from the support using an extraction buffer (TRIS 20mM, 150mM NaCl, 10mM EDTA, 0.2% Triton X10) in the presence of a cocktail of protease inhibitors (Sigma). The proteins thus extracted are centrifuged at 4 ° C. at 10,000 rpm for 10 minutes before being assayed by the BCA protein assay kit (Pierce). The cell lysates are mixed with a denaturation buffer and subjected to SDS-PAGE electrophoresis. The gel used is a 4-12% broth (invitrogen). The proteins are finally transferred to a nitrocellulose membrane (Pal Corporation). The membranes are saturated in 5% PBS-milk, 0.1% tween for 2 h at room temperature, and then incubated at 4 ° C. overnight with a 1 / 1000th anti-clock primary antibody (ABcam). followed by incubation with an IgG-peroxidase secondary anti-rabbit antibody diluted to 1/5000. Revelation is performed by a chemiluminescent substrate. The evaluation of the quantity of proteins expressed in the cells is carried out using chemiimager software (Alpha Innotech Corporation USA). The amount of protein is expressed as a percentage of light intensity compared to the control condition that did not have the treatment.

B) Immunohistochemistry Study Fibroblasts in cultures are cultured in 8-well chambers (labteck) at 37 ° C. in a humidified atmosphere containing 5% CO 2 for 18 h in the presence or absence of the peptide SEQ ID No. 3, diluted 1% (from a 10-4M solution). Untreated cells are cultured at the same time and serve as a control. On the day of labeling, the cells are rinsed, fixed in a mixture (2% glutaraldehyde 2% formaldehyde) for 3 minutes and then rinsed. The primary antibody (ABcam) diluted 1: 250 for 1 hour and a 1: 50 secondary antibody coupled to a fluorochrome for 1 hour are applied. The cells are mounted between slide and coverslip in a suitable mounting medium and observed under an epifluorescence microscope.

Results: The results obtained in western blot show that the treatment with the peptide SEQ ID No. 3, diluted to 1% causes an increase in the amount of Clock protein in the fibroblasts in culture. The results are summarized in the table below. Intensity (%) Experiment 1 Control untreated 100% 1% treatment 133% These results are confirmed by the labeling of the Clock protein on fibroblasts. Conclusion: The peptide SEQ ID No. 3 makes it possible to increase the amount of Clock protein on dermal cells in culture.

EXAMPLE 2 Demonstration of the Activating Effect of the Peptide SEQ ID No. 3 on the Expression of the Clock and Per Protein on Skin Biopsies A study of the activating effect of peptide SEQ ID No. 3 was performed by evaluating the expression of Clock and Per-1 proteins on ex vivo skin biopsies.

Protocol Ex vivo immunolabeling studies made it possible to demonstrate the expression of Clock and Per-1 proteins on skin samples. Human skin samples are cultured at the air / liquid interface. Peptide SEQ ID NO: 3 diluted 1% (from a 10-4M solution) is topically applied to these samples for 48 hours, twice per 24 hours. Skin samples not treated with peptide SEQ ID No. 3 serve as a control. Skin samples are fixed with 10% formaldehyde and embedded in paraffin. Sections of 3 m are made with a microtome. Immunostaining is performed after dewaxing and unmasking of the antigenic sites. Immunolabeling is carried out for the Clock protein by an antibody (ABcam) diluted 1: 250 and a secondary antibody 1 / 50th coupled to a fluorochrome. The immunolabeling is carried out for the Per-1 protein, with a polyclonal antibody (Cosmobio) diluted 1/100 and a secondary antibody 1 / 50th coupled to a fluorochrome. The slides are then mounted in a suitable medium and observed under an epifluorescence microscope (Nikon Eclipse E600).

Results: The results obtained show that the skins treated with peptide SEQ ID No. 3 have a much greater amount of Clock protein than untreated skins. Similarly, it is shown that the skin treated with SEQ ID No. 3 peptide express a higher amount of Per-1 protein untreated skin. The assessment of the marking is visual and summarized in the table below. Untreated Treated with peptide SEQ ID No. 3 diluted to 1% +/- ++ labeling Protein Clock Marking + + PER-1 protein Conclusion: The peptide SEQ ID No. 3 makes it possible to increase the amount of Clock and Per-1 proteins on skin biopsies. EXAMPLE 3 Demonstration of the Activating Effect of the Peptide SEQ ID No. 3 on the Expression of the Clock and Per-1 Protein on Skin Biopsies During Aging A Study of the Activating Effect of the Peptide SEQ ID No. 3, was performed by evaluating the expression of Clock protein and Per-1 protein on skin models, artificially aged in culture. The analysis is carried out after 62 h and 134 h of culture.

Protocol Ex vivo immunolabeling studies made it possible to demonstrate the expression of the Clock and Per proteins on samples of skins aged in culture. Human skin samples are cultured at the air / liquid interface for 62 h and 134 h. Peptide SEQ ID NO: 3 diluted 1% (from a 4M solution) was topically applied to these samples at 2 times per day during the time of the experiment. Skin samples not treated with the peptide SEQ ID No. 3 serve as a control. Skin samples are fixed with 10% formaldehyde and embedded in paraffin. Sections of 31., tm are made microtome. Immunostaining is performed after dewaxing and unmasking of the antigenic sites. Immunostaining is performed for the Clock protein by an antibody (ABcam) diluted 1: 250 and a secondary antibody 1 / 50th coupled to a fluorochrome. Immunolabeling is performed for the Per-1 protein by a polyclonal antibody (Cosmobio) diluted 1/100 and a secondary antibody 1 / 50th coupled to a fluorochrome. The slides are then mounted in a suitable medium and observed under an epifluorescence microscope (Nikon Eclipse E600).

Results: The results obtained show that the labeling of the Clock protein (essentially epidermal) is increased after 62 hours of culture, relative to the untreated control slides. Similarly, the expression of the Per-1 protein is increased after 62 hours of treatment. This marking persists over time since, after 134 hours, the labeling of the Clock protein is greatly increased compared to the untreated control skin. The table below gives a visual assessment of the marking. Untreated Treated with peptide SEQ ID No. 3 diluted to 1% Marking 62 h + + Clock 134 h + ++ Marking 62 h +/- + Per-1 134 h + + Conclusion: The peptide SEQ ID No. 3 allows, d to increase the amount of Clock and Per-1 proteins on skin biopsies treated and artificially aged in culture.

EXAMPLE 4 Demonstration of the Protective Effect of the Peptide SEQ ID No. 3 on Skin Biopsies During Aging In parallel, a study of the protective effect of the peptide SEQ ID No. 3 was carried out by evaluating immunohistology by means of staining of skin sections, the damage caused by an aging of 62 h and 134 h.

Protocol Human skin samples are cultured at the air / liquid interface. Peptide SEQ ID No. 3 diluted 1% (from a 10-4M solution) was applied topically to these samples for 62 h and 134 h. The application is renewed twice a day during the time of the experiment. Untreated skin samples serve as control during the time of the experiment. Skin samples are fixed with 4% formaldehyde and embedded in paraffin. Sections of 3 m are made with a microtome. Tissue staining is done by hematoxylin (which stains nuclei in blue-black) and eosin which is specific for staining of cytoplasm. The morphological structure of the biopsies is then assessed using a transmission microscope.

Results: The results obtained show that the skins not treated with the peptide SEQ ID No. 3 are damaged, the cells are vacuolated, the cells appear to be damaged with cells whose nuclei are highly condensed (apoptotic signs). On the contrary, the skins treated with the peptide SEQ ID No. 3 have a well-preserved morphological structure, the damage due to aging is less visible. In the two experiments, 62 h and 134 h, the peptide SEQ ID No. 3 protects skin biopsies from aging.

Conclusion: The peptide SEQ ID No. 3 makes it possible to demonstrate a protective effect on the structural morphology of skin biopsies subjected to artificial aging in culture. EXAMPLE 7 Preparation of compositions Sunscreen cream: Trade names INCI names% by weight PHASE A Demineralized water Aqua (Water) qsp Pemulen TRI Acrylates / C10-30 Alkyl 0.40 Acrylate Crosspolymer Glycerin Glycerin 3.00 Nipastat Sodium Sodium Methylparaben (and) 0.15 Sodium Ethylparaben (and) Sodium Butyl paraben (and) 20 2940971 -16- Trade Names INCI ~ 7c Sodium Propylparaben (and) Sodium Isobutylparaben PHASE B Parsol MCX Ethylhexyl Methoxycinnamate 7.50 Eusolex 4360 Benzophenone-3 3.00 Parsol 1789 Butyl 2.00 Methoxydibenzoylmethane Myritol 318 Caprylic / Capric Triglyceride 4.00 Emulgade SEV Hydrogenated Palm Glycerides 5.00 (and) Ceteareth-20 (and) Ceteareth-12 (and) Cetearyl Alcohol Propylparaben Propylparaben 0.15 Nacol 16-98 Cetyl Alcohol 1.00 PHASE C TEA Triethanolamine 0.20 PHASE D Peptide SEQ ID NO: 3 3 ppm Perfume Fragrance qsp Colorant qsp The constituents of phase A and phase B are heated separately between 70 ° C and 75 ° C vs. Phase B is emulsified in phase A with stirring. Phase C is added at 45 ° C, increasing stirring. Phase D is then added when the temperature is below 40 ° C. Cooling is continued up to 25 ° C with vigorous stirring.

Claims (17)

REVENDICATIONS1. Peptide Compound of the Following General Formula (I): R1- (AA) ä-X1-His-Ser-Gly-Tyr-Glu-X2-(AA) p û R2 wherein X1 is valine, isoleucine or zero, X2 is an alanine, a proline, or is zero, AA represents any amino acid, or a derivative thereof, and n and p are integers between 0 and 4, R1 represents the primary amine function of the amino acid N-terminal, free or substituted by a protective group may be chosen from an acetyl group, a benzoyl group, a tosyl group or a benzyloxycarbonyl group, R2 represents the hydroxyl group of the carboxyl function of the C-terminal free amino acid or substituted with a protecting group which may be selected from a C 1 to C 20 alkyl chain, or an NH 2, NHY or NYY group with Y representing a C 1 to C 4 alkyl chain, said sequence of general formula (I) consisting of at 15 amino acid residues, said sequence of general formula (I) may comprise substitutions of amino acids X1 and X2 by other chemically equivalent amino acids. 2. Peptide compound according to claim 1, characterized in that the peptide of general formula (I) has at least one functional group protected by a protective group, this protecting group being either an acetylation of the amino-terminal end, or a amidation or esterification of the carboxy terminus, or both. 3. Peptide compound according to one of claims 1 or 2, characterized in that it corresponds to one of the following formulas: (SEQ ID No. 1) Ile-His ûSer ûGly ûTyr ûGlu -NH2 (SEQ ID No. 2) Arg ûVal - His ûSer ûGly ûTyr ûGlu ûAla ûArg (SEQ ID NO: 3 His ûSer ûGly ûTyr ûGlu -NH2 (SEQ ID NO: 4) Gln ûLeu - His ûSer ûGly ûTyr ûGlu ûPro - NH235 (SEQ ID No 5) Ile ûArg - His ûSer ûGly ûTyr ûGlu ûPro (SEQ ID No. 6) His ûSer ûGly ûTyr ûGlu ûAla ûPro 4. Peptide compound according to claim 3, characterized in that it corresponds to the sequence (SEQ ID No. 2). 5. Peptide compound according to claim 3, characterized in that it corresponds to the sequence (SEQ ID No. 3). 10 6. Peptide compound according to one of the preceding claims, characterized in that it is used as a medicament. 7. Cosmetic composition comprising as active principle said peptide compound according to one of claims 1 to 5. 8. Cosmetic composition according to claim 7, characterized in that it is in a form suitable for topical application comprising a cosmetically acceptable medium. 20 9. Composition according to one of claims 7 or 8, characterized in that said peptide compound is present in the composition at a concentration between 0.0005 and 500 ppm approximately, and preferably at a concentration between 0.01 and 5 ppm. 25 10. Composition according to any one of claims 7 to 9, characterized in that said peptide active ingredient is solubilized in one or more solvents, such as water, glycerol, ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diglycols, cyclic polyols, petroleum jelly, a vegetable oil or any mixture of these solvents. 30 11. Composition according to any one of claims 7 to 10, characterized in that it further contains at least one other active ingredient promoting the action of said peptide active principle. 15 12. Composition according to claim 11, characterized in that said active ingredient is an anti-radical agent or antioxidant, or an agent stimulating the synthesis of dermal macromolecules, or an agent stimulating the energy metabolism. 13. Use of a composition according to any one of claims 7 to 12, characterized in that said composition prevents or treat the cutaneous signs of aging. 14. Use of a composition according to the preceding claim, characterized in that said composition protects the skin against attacks due to UV radiation. 15. Use of an effective amount of peptide active ingredient, as defined in one of claims 1 to 6, for the preparation of a pharmaceutical composition for preventing or controlling pathologies related to oxidation processes. 16. Cosmetic treatment process, characterized in that a composition containing an effective amount of peptide active ingredient, as defined in one of Claims 1 to 5, is applied topically to the skin or integuments to be treated in order to prevent or treat treat the signs of skin aging or protect the skin against UV radiation. 17. Cosmetic treatment method, as defined in the preceding claim, characterized in that the composition is applied before bedtime to respect the circadian rhythm of the skin to obtain a rejuvenating effect on the skin.