WO2010112713A2

WO2010112713A2 - Novel proteasome-activating lightening peptides and compositions containing same

Info

Publication number: WO2010112713A2
Application number: PCT/FR2010/000281
Authority: WO
Inventors: Claude Dal Farra; Nouha Domloge; Jean-Marie Botto
Original assignee: Isp Investments Inc.
Priority date: 2009-04-02
Filing date: 2010-04-01
Publication date: 2010-10-07
Also published as: FR2944015A1; FR2944015B1; WO2010112713A3

Abstract

The invention relates to depigmenting, lightening and/or whitening peptidic compounds having formula (I): R₁-X₁-Arg-Lys-GIy-X₂-R₂. In addition, the invention relates to (i) a cosmetic or pharmaceutical composition containing at least one peptide having formula (I) in a cosmetically or dermatologically acceptable medium and (ii) the use thereof in order to dipigment, lighten and/or whiten the skin and to prevent or treat hyperpigmentation blemishes as well as the cutaneous signs of photoaging. The invention further relates to a cosmetic treatment method using said peptidic compounds.

Description

NOVEL PROTEASOME ACTIVATORY LIGHTENING PEPTIDES AND COMPOSITIONS CONTAINING SAME

The present invention relates to peptide compounds of general formula

R ₁ - X ₁ - Arg - Lys - GIy - X ₂ - R ₂ as lightening, depigmenting and / or whitening agents, as well as their uses in cosmetics and / or pharmaceuticals. Said compounds also make it possible to prevent and / or treat cutaneous signs of hyperpigmentary order due to photoaging. The compositions comprising said peptide compounds finally make it possible to treat hyperpigmentation spots of various origins.

In humans, the color of the hair and skin is related to individual factors (ethnic origin, gender, age, etc.) and environmental factors (including the seasons of the year, the area of habitation, etc.). It is mainly determined by the nature and concentration of melanin produced by melanocytes. Melanin has the property of protecting skin cells from the deleterious effects of UV radiation and slowing skin photoaging. Melanocytes are specialized cells that, via particular organelles, melanosomes, synthesize melanin. The synthesis of melanin or melanogenesis is a complex process whose precise mechanisms are not yet elucidated and which schematically involves the following steps:

Tyrosine> - Dopa * ^• Dopaquinone ^ Dopachrome * ^• Melanin.

This melanin plays indeed a fundamental role in the determination of the color of the skin. It is synthesized by large dendritic cells: melanocytes, cells located in the basal layer of the epidemic. Melanin exists in two different forms: phaeomelanin, yellow pigment, and black eumelanin. It is the different proportions and the size of these pigments, not to mention the carotenoids and the micro-blood circulation, which give the skin its great diversity of colors.

The production of melanin, as well as its transport, is regulated by various factors such as, for example, UV radiation, hormones or chemicals. Thus, an increase in exposure to UV radiation causes the synthesis of pigments and results in a darkening of the skin. Disturbances of this pigmentation, more or less benign, may appear. They are manifested, for example, by freckles, moles, diffuse spots such as pregnancy spots, chloasma, melasma, as well as other hyperpigmentary disorders such as lentigo. Other spots of hyperpigmentation may be due for example to poor healing especially in individuals with dark phenotype, or they may be due to the use of photosensitizing drugs etc. But aging can also modulate skin pigmentation. Thus, some people may see spots on the skin, more or less dark or colored, conferring areas of heterogeneous coloring forming spots of senescence or ephelides. Finally, in certain populations of Asian or African type, lightening cosmetic treatments are sought in order to obtain a clear and uniform complexion.

The use of inhibitors or regulators of melanin synthesis, as well as any other depigmenting and / or whitening product, is therefore particularly advantageous in cosmetology and / or dermatology. This use is not only interesting when a true depigmentation of the skin is sought, as in the case of bleaching heavily pigmented skin or when inhibiting hyperpigmented skin areas resulting in an unsightly appearance of the skin; It is also used in certain applications aimed at lightening the complexion, giving luminosity to the skin or giving radiance to the surface tissues.

To date, many molecules have been proposed with more or less efficiency. Among these molecules, mention may be made of phenol derivatives such as hydroquinone and resorcinol which inhibit a series of reaction of the conversion of L-tyrosine to melanine by inhibition of the tyrosinase activity (Takano, 1984). There may also be mentioned L-ascorbic acid and its derivatives, magnesium ascorbyl acetate, kojic acid or lactic acid.

But most of the products currently on the market are toxic and / or not sufficiently effective. For example, hydroquinone is irritating and cytotoxic to the melanocyte. Kojic acid for example is not stable in solution, etc. There is therefore a need for a new whitening agent which does not have the disadvantages of existing ones but which would be equally effective. Thus, other ways have been explored in order to find a new depigmenting agent having an action on both the enzyme tyrosinase and melanin.

Surprisingly, the Applicant has discovered that peptide compounds of formula R ₁ -X ₁ -Arg-Lys-GIy-X ₂ -R ₂ were very good bleaching agents and showed good depigmenting activity without being toxic. These peptide compounds are in fact proteasome activating compounds.

The ubiquitin-proteasome pathway plays a fundamental role in a very large number of biological processes. Indeed, the mechanisms of protein degradation by the proteasome are involved in important cellular mechanisms such as DNA repair, the control of gene expression, the regulation of cell cycle progression, the control of quality of neosynthesized proteins, apoptosis or immune response (Glickman and Ciechanover, 2002).

The proteasome present in human cells is a very large multi-protein complex present in the cytoplasm and the nucleus. Purified forms of the proteasome include 2 large subunits; on the one hand, a proteolytic core called proteasome 2OS and, on the other hand, a 19S regulatory complex that binds to each of the two ends of the 2OS proteasome (Coux et al., 1996;

Glickman and Coux, 2001). The 2OS proteasome is a hollow cylinder-shaped particle, composed of 28 alpha and beta subunits, distributed in 4 heptameric rings. The peptidase activities are present on the inner surface of the cylinder and influence allosterically. Three proteolytic activities ("trypsin, chymotrypsin and caspase-like") have been associated with the 2OS proteasome and contribute to the destruction of proteins as inactive peptides of 3 to 20 amino acids. In addition to the 2OS proteasome, the 26S proteasome comprises the 19S regulator complex of 0.7 MDa consisting of about 20 subunits. Recent immunopurification studies have shown that other proteins can be associated with the 2OS and 19S proteasome (eg the 1 IS regulatory complex).

Given the diversity of cellular processes controlled by the degradation of proteins, it is not surprising to find that alterations of the ubiquitin-proteasome pathway are at the origin, or closely related to several genetic diseases and many pathologies humans such as cancer colorectal, lymphoma, inflammatory syndromes, neurodegenerative diseases such as Parkinson's or Alzheimer's ...

Many studies have been conducted in recent years on the role of the proteasome in aging skin. One of the recently explored pathways was the proteasome and its action on the degradation of proteins involved in melanogenesis. Experiments have shown that the degradation of the tyrosinase enzyme by the proteasome was activated by an algal extract on human melanocytes (Nizard et al., Antioxid Redox Signal, 2006, 1-2: 136-143).

A composition comprising an extract of silybin, Bletilla striata and Iris sanguinea capable of increasing the activity of the proteasome and having an effect on the pigmentation of the skin has been disclosed in a patent application (US 12 / 088 919).

Thus the Applicant has discovered that compounds of formula R ₁ - X ₁ - Arg - Lys - GIy - X ₂ - R ₂ were capable of activating the proteasome and could thus depigment, lighten or whiten the skin and the dander.

Accordingly, the present invention firstly relates to a peptide proteasome activator peptide compound of the following general formula (I): R ₁ - X ₁ -Arg - Lys - GIy - X ₂ - R ₂

In which,

X ₁ represents an isoleucine, a leucine, a proline, a valine, or is equal to zero,

X ₂ represents a cysteine, a glutamic acid, a glutamine, a histidine, a methionine, a phenylalanine, a tyrosine, a threonine, or is equal to zero,

R 1 represents the primary amino function of the N-terminal amino acid, free or substituted with a protective group that may be chosen 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, substituted by 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 3 to 5 amino acid residues, said sequence of general formula (I) possibly comprising substitutions of amino acids X ₁ and X ₂ by other chemically equivalent amino acids.

The subject of the present invention is a cosmetic composition comprising, as active ingredient, said peptide compound of formula (I).

In addition, the third subject of the present invention is the use of a cosmetic composition comprising said peptide compound of formula (I) for improving the proteasome degradation of damaged proteins and thus preventing and / or treating hyperpigmentation spots.

Finally, the fourth subject of the present invention is a process for cosmetic treatment of the skin or integuments with the aid of a composition comprising said peptide compound of formula (I).

The subject of the present invention is a proteasome activator peptide compound of the following general formula (I):

R ₁ - Xi Arg - Lys - Gly - X ₂ - R ₂ wherein, X represents isoleucine, leucine, proline, valine, or is zero,

R 1 represents the primary amino function of the N-terminal amino acid, free or substituted by a protective group which may be chosen 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, 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 an alkyl chain. from C1 to C4, said sequence of general formula (I) consisting of 3 to 5 amino acid residues, said sequence of general formula (I) may comprise substitutions of amino acids X ₁ and X ₂ by other chemically equivalent amino acids, characterized in that it is lightening, depigmenting and / or whitening.

Peptide compound "proteasome activator" means any peptide or biologically active derivative capable of increasing the activity of the proteasome, either by increasing the protein synthesis of the proteasome subunits (by direct or indirect modulation of the expression gene) or by other biological processes such as the stabilization of the subunits constituting the proteasome or the stabilization of messenger RNA transcripts.

The peptide compound according to the invention is characterized in that it makes it possible to activate the degradation by the proteasome of the damaged proteins involved in melanogenesis. "Damaged proteins" means proteins that have undergone oxidation reactions due to reactive oxygen species (free radicals), glycated or conjugated proteins with products derived from lipid peroxidation, etc. By "involved in melanogenesis" is meant any protein directly or indirectly involved in the synthesis of melanin, such as the enzyme tyrosinase, or even melanin itself.

In a first preferred embodiment, the peptide compound is protected by acylation or acetylation of the amino-terminus and / or the carboxy-terminus.

In a second preferred embodiment, the peptide compound corresponds to one of the following formulas:

(SEQ ID NO: 1) De - Arg - Lys - GIy - NH ₂

(SEQ ID NO: 2) Leu-Arg-Lys-GIy-Met-NH ₂

(SEQ ID NO: 3) Pro-Arg-Lys-GIy-Thr-NH ₂

(SEQ ID NO: 4) Val - Arg - Lys - GIy - Ph - NH ₂ (SEQ ID NO: 5) Val - Arg - Lys - GIy - Tyr - NH ₂

(SEQ ID NO: 6) Arg-Lys-GIy-NH ₂

Preferably, the peptide compound according to the invention corresponds to the sequence ID No. 2, that is to say Leu-Arg-Lys-GIy-Met-NH ₂ . In another preferred embodiment, the peptide compound according to the invention corresponds to the sequence ID No. 6, that is to say Arg-Lys-GIy-NH _2.

The invention also relates to homologous forms of these sequences. The term "homologue" denotes, according to the invention, any peptide sequence identical to at least 50%, or preferably at least 80%, and even more preferably to at least 90% of said peptide sequence, chosen from SEQ ID sequences. No. 1 to SEQ ID No. 6. "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.

The optimal alignment is achieved using local homology algorithms such as those used by the BLAST P computer software available on the NCBI site.

The term "homologue" can also refer to a peptide which differs from the sequence of a peptide of sequence SEQ ID No. 1 to SEQ ID No. 6 by the substitution of chemically equivalent amino acids, that is to say by the 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 Asp and Glu acid residues; between Asn and GIn; and between the basic residues Lys and Arg; or between the aromatic residues Phe and Tyr. The amino acids constituting the peptide according to the invention may be in the Lévogyre configuration, that is to say L- and / or Dextrogyre that is to say D-. The peptide according to the invention can therefore be in L-, D- or DL- form.

The term "peptide" or "peptide compound" refers to a sequence of two or more amino acids linked together by peptide bonds or modified peptide bonds. This term is equivalent to the term "active ingredient" which will be used as well.

By "peptide" or "peptide compound" 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 or synthetic peptide whose sequence is totally or partially constituted by the sequence of the peptide described above.

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 forms of biologically compatible protection can be envisaged. They are well known to those skilled in the art such as, for example, the acylation or acetylation of the amino and / or carboxy terminal ends. 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 a single or double protected form. Preferably, for the protection of the hydroxyl function of the carboxy-terminal end, an amidation by an NYY group with Y representing a C 1 to C ₄ alkyl chain, or esterification with an alkyl group is used. 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) as active principle. Preferably, the compositions according to the invention are in a form suitable for topical application comprising a cosmetically acceptable medium. The term "cosmetically acceptable" means media which are 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 solubilized in one or several 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.

According to yet another advantageous embodiment, the active principle according to the invention is solubilized in a vector such as liposomes or adsorbed on organic powdery polymers, mineral supports such as talcs and bentonites, and more generally solubilized in, or fixed on any physiologically acceptable vector.

The compositions intended to be applied to the skin may be in the form of an aqueous or aqueous-alcoholic solution, a water-in-oil or oil-in-water emulsion, a microemulsion, an aqueous or anhydrous gel, a serum or a dispersion of vesicles, patch, cream, spray, ointment, ointment, lotion, colloid, solution, suspension or others. 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 eyelashes, eyebrows or hair, or care for nails such as varnishes .

In a particular embodiment, the composition according to the invention further contains at least one other active ingredient promoting the action of said peptide compound. The classes of ingredients having an activity in the field of lightening agents such as desquamating agents may be mentioned, in a nonlimiting manner; soothing agents, organic or inorganic photoprotective agents, moisturizing agents; other depigmenting agents, tyrosinase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; agents acting on the energetic metabolism of cells; other depigmenting peptides, plant hydrolysates, anti-aging agents, and mixtures thereof. In addition, additives such as thickening agents, emulsifiers, humectants, emollients, perfumes, antioxidants, film-forming agents, chelating agents, sequestering agents, conditioning agents, etc. may be added to the composition.

In all cases, the skilled person will ensure that these adjuvants and their proportions are chosen in such a way as not to harm the properties advantageous of the composition according to the invention. These adjuvants may, for example, be between 0.01 and 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.

Finally, the composition as described makes it possible to increase the activity of the proteasome and to improve the proteasome degradation of the damaged proteins involved in melanogenesis.

A third subject of the invention relates to the use of a cosmetic composition comprising said peptide compound and a cosmetically acceptable medium for depigmenting, lightening and / or whitening the skin.

The composition according to the invention also makes it possible to prevent and / or treat hyperpigmentation spots such as melasma, chloasma, actinic lentigo, solar lentigines, ephelides, accidental hyperpigmentation spots, hyperpigmentation spots. post-cicatricial. Another subject of the invention relates to the use of a composition comprising said peptide compound for treating and / or preventing cutaneous signs of hyperpigmentary order due to photoaging. "Photo-aging" means the premature aging of the skin caused by prolonged and cumulative exposure to the sun. Finally, another subject of the invention relates to the use of a cosmetic composition according to the invention for increasing the activity of the proteasome and improving the degradation by the proteasome of the damaged proteins involved in melanogenesis.

A final subject of the present invention relates to a cosmetic treatment method characterized in that a composition comprising an effective amount of peptide compound according to the invention for depigmenting, lightening, is applied topically to the skin or integuments to be treated. and / or whiten the skin or integuments. Moreover, this cosmetic treatment process is also intended to to prevent and / or treat cutaneous hyperpigmentary signs due to photoaging.

The following examples describe and demonstrate the effectiveness of peptide compounds as described according to the invention. The cosmetic formulation cited is representative of the invention but is given by way of illustration only and should not be construed as a limitation of the present invention.

Example 1: Demonstration of the Depigmenting Effect of the Asset by Ex Vivo Tests.

The depigmenting activity of the active ingredient of sequence ID No. 6 was demonstrated on a skin sample.

Biopsies 6 mm in diameter are taken from human skin samples. These biopsies are maintained in survival ex vivo by culture in the presence of a specific medium (DMEM 1 g / L, HAMF 12, FCS and antibiotics) on inserts deposited in 6-well plates. The biopsies are then pretreated for 24 hours with the active ingredient at a concentration of 3% at a rate of 2 applications per day. Other skin samples will not be pretreated with the asset and will serve as a control condition. Subsequently, the biopsies are subjected to UVB irradiations at a rate of 100 mJ / cm ² . The pre-treated biopsies are treated again for 24 hours with the active ingredient at a concentration of 3% at 2 applications per day. After this second treatment, a quantitative evaluation of the amount of melanin present in the epidermis of the skin samples is performed histologically, under an optical microscope, after staining according to the Fontana-Masson method. For this, skin biopsies are included in the paraffin and histological sections of 4 microns thick are made. These sections are then stained by the Fontana-Masson technique: the slides are deparaffinized, hydrated and then treated with a solution of silver ammonia. After passing for two minutes in the microwave, the slides are rinsed, treated with sodium thiosulphate, rinsed again and counter-stained with hematoxylin before being dehydrated and mounted under coverslips thus allowing visualization under an optical microscope melanin present in the epidermis. Results:

Before UVB irradiation, the untreated skins have a higher level of pigmentation compared to the skins treated with the active. After UVB irradiation, the skins treated with the active have a significantly lower level of pigmentation compared to the untreated skins of the control condition. Therefore, these results allow us to conclude that in the absence of UVB irradiation, the active agent decreases the melanin level compared to the untreated skin sample. Furthermore, the melanin synthesis induced by the UVB irradiations is very much attenuated when the skin samples are pretreated with the active ingredient. Thus, the active agent according to the invention makes it possible to significantly reduce the pigmentation of the skin and makes it possible to obtain an inhibition of melanin synthesis.

EXAMPLE 2 Depigmenting Cosmetic Composition with Solar Filter

Claims

Peptide compound activator of the proteasome of the following general formula (I):

R ₁ - X ₁ - Arg - Lys - GIy - X ₂ - R ₂ In which, o

R ₁ represents the primary amino function of the N-terminal amino acid, free or substituted with a protective group that may be chosen 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 substituted with a protecting group which may be chosen 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 3 to 5 amino acid residues, said sequence of general formula (I) may comprise substitutions of amino acids X ₁ and X ₂ by other amino acids chemically equivalent.

Peptide compound according to claim 1, characterized in that it corresponds to one of the following formulas:

(SEQ ID NO: 1) Ile - Arg - Lys - GIy - NH ₂ (SEQ ID NO: 2) Leu - Arg - Lys - GIy - Met - NH ₂ (SEQ ID NO: 3) Pro - Arg - Lys - GIy - Thr - NH ₂ (SEQ ID NO: 4) Val - Arg - Lys - GIy - Ph - NH ₂ (SEQ ID NO: 5) Val - Arg - Lys - GIy - Tyr - NH ₂

(SEQ ID NO: 6) Arg-Lys-GIy-NH ₂

3. Peptide compound according to one of claims 1 or 2 characterized in that it is used as a drug.

4. Cosmetic composition comprising as active principle said peptide compound according to one of claims 1 or 2.

5. Cosmetic composition according to claim 4, characterized in that it is in a form suitable for topical application comprising a cosmetically acceptable medium.

6. Composition according to one of claims 4 or 5, 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.

7. Composition according to any one of claims 4 to 6, characterized in that said peptide compound 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.

8. Composition according to any one of claims 4 to 7, characterized in that it further contains at least one other active ingredient promoting the action of said peptide compound.

9. Composition according to claim 8, characterized in that said active ingredient is an agent having an activity in the field of lightening agents such as desquamating agents; soothing agents, organic or inorganic photoprotective agents, moisturizing agents; other depigmenting agents, tyrosinase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; agents acting on the metabolism energy of cells; other depigmenting peptides, plant hydrolysates, anti-aging agents, and mixtures thereof.

10. Use of a cosmetic composition comprising said peptide compound as defined in one of claims 1 or 2 and a cosmetically acceptable medium for depigmenting, lightening and / or whitening the skin.

11. Use of a composition according to claim 10 for preventing and / or treating hyperpigmentation spots such as melasma, chloasma, actinic lentigo, solar lentigines, ephelides, accidental hyperpigmentation spots, stains. post-scarring hyperpigmentation.

12. Use of a composition according to claim 10 for treating and / or preventing cutaneous signs of hyperpigmentary order due to photo-aging.

13. Use of a cosmetic composition comprising said peptide compound as defined in one of claims 1 or 2 for increasing the activity of the proteasome and improving the proteasome degradation of damaged proteins involved in melanogenesis.

14. Cosmetic treatment process, characterized in that a composition comprising an effective amount of peptide compound as active principle as defined in one of claims 1 or 2 is applied topically to the skin or integuments to be treated. to depigment, brighten and / or whiten skin or integuments.

15. Cosmetic treatment method, as defined in claim 14, for preventing and / or treating cutaneous signs of hyperpigmentary order due to photoaging.