FR2897268A1 - Use of a copolymer of styrenic monomer and carboxylic diacid with ethylene unsaturation, to depigment and/or to bleach the skin, preferably to eliminate the pigmentary spots, age spots and/or as anti-pigmenting agent - Google Patents

Abstract

Use of a copolymer of styrenic monomer and carboxylic diacid with ethylene unsaturation, as agent to depigment and/or to bleach the skin, preferably to eliminate the pigmentary spots, age spots and/or as anti-pigmenting agent. An independent claim is included for a cosmetic process to depigment and/or to clear up skin having pigmentation spots, comprising applying a composition containing the copolymer in a medium, on the skin, where the composition is free from hydrophilic active ingredient sensitive to oxidation. ACTIVITY : Dermatological. MECHANISM OF ACTION : Melanogenesis modulator. The ability styrene-maleic anhydride copolymer to modulate the melanogenesis was tested in human co-culture. The results showed that the copolymer exhibited an IC50 value of 60 mu M.

Description

The present invention relates to the use of a styrene copolymer and

  of ethylenic dicarboxylic acid as skin depigmenting agent, as well as a method of depigmenting the skin.

  The color of human skin is a function of various factors including seasons of the year, race and sex; it is mainly determined by the nature and concentration of melanin produced by melanocytes. Melanocytes are specialized cells that, via particular organelles, melanosomes, synthesize melanin. In addition, at different times in their lives, some people see darker and / or more colored spots on the skin and especially on the hands, giving the skin a degree of heterogeneity. These spots are also due to a high concentration of melanin in keratinocytes located on the surface of the skin.

  The use of harmless topical depigmenting substances with good efficacy is particularly sought for treating regional hyperpigmentations by melanocytic hyperactivity such as idiopathic melasmas, occurring during pregnancy ("pregnancy mask" or chloasma) or a oestro-progestative contraception, hyperpigmentations localized by hyperactivity and benign melanocyte proliferation, such as senile pigmentary spots known as actinic lentigo, accidental hyperpigmentations, possibly due to photosensitization or post-injury healing, as well as certain leukoderma, such as vitiligo. For the latter (the scarring may result in a scar giving the skin a whiter appearance), failing to repigment the damaged skin, it completes depigmenting the areas of residual normal skin to give the whole skin a homogeneous white color.

  The mechanism of formation of skin pigmentation, that is, the formation of melanin, is particularly complex and schematically involves the following main steps: Tyrosine ---> Dopa ---> Dopaquinone - -> Dopachrome ---> Melanine Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxido-reductase EC 1.14.18.1) is the essential enzyme involved in this series of reactions. In particular, it catalyzes the conversion reaction of tyrosine to Dopa (dihydroxyphenylalanine) thanks to its hydroxylase activity and the conversion reaction of Dopa to dopaquinone by virtue of its oxidase activity. This tyrosinase only acts when it is maturing under the influence of certain biological factors.

  A substance is recognized as depigmenting if it acts directly on the vitality of the epidermal melanocytes where the melanogenesis takes place, and / or if it interferes with one of the stages of melanin biosynthesis either by inhibiting one of the enzymes involved in melanogenesis, or by interposing itself as a structural analogue of one of the chemical compounds of the melanin synthesis chain, which chain can then be blocked and thus ensure depigmentation.

  The substances most used as depigmenting agents are more particularly hydroquinone and its derivatives, in particular its ethers such as monomethyl ether and hydroquinone monoethyl ether. These compounds, although they have a certain effectiveness, are unfortunately not free of side effects because of their toxicity, which can make their use difficult, even dangerous. This toxicity comes from the fact that they interfere with the fundamental mechanisms of melanogenesis by killing cells that may then disturb their biological environment and therefore force the skin to evacuate them by producing toxins.

  Thus, hydroquinone is a particularly irritating and cytotoxic compound for melanocytes, whose replacement, total or partial, has been considered by many authors.

  Thus, substances which do not intervene in the mechanism of melanogenesis but which act upstream on tyrosinase by preventing its activation and are therefore much less toxic are thus sought. The kojic acid which complexes copper present in the active site of this enzyme is commonly used as an inhibitor of tyrosinase activation. Unfortunately, this compound is unstable in solution, which somewhat complicates the manufacture of the composition. There is still a need for a new human skin whitening agent that is as effective as those known, but does not have the disadvantages thereof, i.e., non-irritating, non-toxic and / or non-allergenic for the skin. In this regard, it has surprisingly and unexpectedly been found that certain polymers of styrene and ethylenic dicarboxylic acid have good depigmenting and anti-pigmenting activity. More precisely, the subject of the invention is therefore the use as agent (and especially as sole agent) for depigmenting and / or whitening the skin, in particular for eliminating pigment spots, senescence spots and / or as an anti-pigmenting agent, a copolymer of styrene monomer and ethylenically unsaturated dicarboxylic acid.

  The subject of the invention is also a cosmetic process for depigmenting and / or lightening skin with pigmentation spots comprising applying to the skin a composition comprising, in a physiologically acceptable medium, at least one styrene monomer copolymer and of ethylenically unsaturated dicarboxylic acid as described above, the composition being free of hydrophilic active ingredient sensitive to oxidation. The method is particularly suitable for removing brownish pigment spots and / or senescence spots, and / or for lightening browned skin. The invention also relates to the use of a copolymer of styrene monomer and ethylenically unsaturated dicarboxylic acid as described above for the manufacture of a dermatological composition for depigmenting and / or bleaching the skin, the composition being free of of a hydrophilic active ingredient sensitive to oxidation.

  The styrene / dicarboxylic acid copolymers used according to the invention according to the invention make it possible to effectively depigment and / or lighten the skin of human beings. They are intended, in particular, to be applied to the skin of individuals presenting brownish pigmentation spots, senescence spots, or on the skin of individuals wishing to combat the appearance of a brownish color resulting from melanogenesis, by example as a result of exposure to ultraviolet radiation. The copolymer used according to the invention is a copolymer of styrene monomer and of ethylenically unsaturated dicarboxylic acid.

  As styrene monomer, there may be mentioned styrene, alpha-methyl styrene, and preferably styrene.

  Ethylenically unsaturated dicarboxylic acid monomers that may be mentioned include maleic acid, itaconic acid, or their hydrolysed anhydride derivative after polymerization (in particular maleic anhydride or itaconic anhydride).

  Copolymers which are more particularly suitable for the implementation of the invention are copolymers obtained by copolymerization of one or more maleic or maleic anhydride units followed by their hydrolysis. The maleic anhydride or itaconic acid anhydride units may be partially or fully hydrolysed.

  Said copolymer is preferably in salt form, especially in the form of alkaline salts, for example in the form of ammonium, sodium, potassium or lithium salts, and preferably in the form of sodium salt. In an advantageous aspect of the invention, the copolymer has a mole fraction in dicarboxylic acid unit with ethylenic unsaturation of between 0.1 and 0.9, preferably between 0.4 and 0.9, and more preferably between 0.4. and 0.6. Preferably said polymer has a solubility in water at 25 C greater than or equal to 2 g / l.

  The weight average molar mass of the styrene / ethylenically unsaturated dicarboxylic acid copolymer is preferably between 1000 and 500 000 and preferably between 1000 and 50 000. Preferably, a copolymer of styrene and maleic acid (or hydrolyzed maleic anhydride), in particular in a molar ratio styrene / maleic acid ranging from 40/60 to 60/40, in particular equal to 50/50. For example, it is possible to use styrene / maleic anhydride copolymer (50/50), hydrolyzed in the form of 30% ammonium salt in water sold under the reference SMA1000H8 by the company CRAY VALLEY or the styrene / maleic anhydride copolymer. (50/50) hydrolysed in the form of 40% sodium salt in water sold under the reference SMA1000HNa by the company Cray Valley (and having the INCI name: sodium styrene / MA copolymer). The copolymer is present in the composition used according to the invention in sufficient quantity to obtain the desired effect, that is to say in an amount sufficient to depigment the skin. The copolymer is preferably present in a content ranging from 0.1% to 40% by weight, relative to the total weight of the composition, more particularly in a content ranging from 0.1% to 20% by weight, and preferably ranging from 0.1% to 10% by weight, relative to the total weight of the composition. According to a particular embodiment of the invention, the copolymer of styrenic monomer and ethylenically unsaturated dicarboxylic acid previously described is used according to the invention not being associated with a hydrophilic active ingredient sensitive to oxidation. By hydrophilic active is meant a compound having a solubility in water of at least 0.25% at room temperature (25 C). By hydrophilic active agent sensitive to oxidation is meant any hydrophilic active agent of natural or synthetic origin likely to undergo degradation by an oxidation mechanism. This oxidation phenomenon can have several causes, in particular the presence of oxygen, light, metal ions, a high temperature, or certain pH conditions.

  In particular, the hydrophilic active agent sensitive to oxidation may be ascorbic acid or a derivative thereof chosen in particular from 5,6-di-O-dimethylsilylascorbate, the potassium salt of dl-alpha-tocopheryl- dl-ascorbyl-phosphate, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl glucoside; phloroglucinol; kojic acid. The composition used according to the invention comprises, in a physiologically acceptable medium, at least one copolymer of styrene and hydrolysed maleic anhydride as defined above.

  In particular the composition is suitable for topical application to the skin. The physiologically acceptable medium will preferably be a cosmetically or dermatologically acceptable medium, that is to say without odor, color or unpleasant appearance, and which does not generate tingling, tightness or redness unacceptable to the user.

  By physiologically acceptable medium, an environment compatible with keratin materials of human beings such as the skin, the mucous membranes, the nails, the scalp and / or the hair is understood.

  The composition used according to the invention may be intended for a cosmetic or pharmaceutical application, particularly dermatological. Preferably the composition according to the invention is intended for a cosmetic application.

  The composition may then comprise all the constituents usually employed in the intended application. It may especially be mentioned water, solvents, oils of mineral, animal and / or vegetable origin, waxes, pigments, fillers, surfactants, cosmetic or dermatological active agents, UV filters, polymers, gelling agents, preservatives.

  Of course, those skilled in the art will take care to choose this or these optional additional compounds, and / or their quantity, in such a way that the advantageous properties of the compounds according to the invention are not, or not substantially, impaired by the addition envisaged. .

  The composition used according to the invention may be in any galenical form normally used in the cosmetic and dermatological fields; it may especially be in the form of an aqueous solution, hydroalcoholic, optionally gelled, a dispersion of the lotion type optionally bi-phased, an oil-in-water or water-in-oil emulsion or multiple, a aqueous gel, an oil dispersion in an aqueous phase using spherules, these spherules may be polymeric nanoparticles such as nanospheres and nanocapsules or, better, lipid vesicles of ionic type and / or non-ionic, or else a powder.

  When the composition is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The oils, emulsifiers and optional coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the field under consideration. The emulsifier and the coemulsifier are present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

  This composition may be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a mousse . It can optionally be applied to the skin in the form of an aerosol. It can also be in solid form, and for example in the form of a stick.

  In an advantageous aspect of the invention, the compositions used may further comprise at least one desquamating agent, and / or at least one soothing agent, and / or at least one organic photoprotective agent and / or at least one mineral photoprotective agent.

  By "desquamating agent" is meant any compound capable of acting: either directly on the desquamation by promoting exfoliation, such as the 13-hydroxy acids, in particular salicylic acid and its derivatives (including noctanoyl 5 -salicylic); α-hydroxy acids, such as glycolic, citric, lactic, tartaric, malic or mandelic acids; urea; gentisic acid; oligofucoses; cinnamic acid; Saphora japonica extract;

  or on the enzymes involved in the desquamation or degradation of corneodesmosomes, glycosidases, stratum corneum chymotryptic enzyme (SCCE) or even other proteases (trypsin, chymotrypsin-like). Mention may be made of the chelating agents for mineral salts: EDTA; N-acyl-N, N ', N', ethylene diaminetriacetic acid; aminosulfonic compounds and in particular (N-2-hydroxyethylpiperazine-N-2-ethane) sulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid derivatives (procysteine); glycine-type alpha amino acid derivatives (as described in EP-0 852 949, as well as the sodium methyl glycine diacetate marketed by BASF under the trade name TRILON M); honey ; sugar derivatives such as O-octanoyl-6-D-maltose and N-acetyl glucosamine.

  As soothing agents that may be used in the composition used according to the invention, mention may be made of: pentacyclic triterpenes and plant extracts (eg Glycyrrhiza glabra) containing them, such as 13-glycyrrhetinic acid and its salts and / or derivatives thereof glycyrrhetinic acid monoglucuronide, stearyl glycyrrhetinate, 3-stearoyloxy glycyrrhetic acid), ursolic acid and its salts, oleanolic acid and its salts, betulinic acid and its salts, an extract of Paeonia suffruticosa and / or lactiflora, salicylic acid salts and in particular zinc salicylate, Codif's phycosaccharides, Laminaria saccharina extract, Canola oil, bisabolol and chamomile extract, allantoin, Sepivital EPC (Vitamin E and C) diesterphosphoric acid from Seppic, omega 3 unsaturated oils such as rosehip musca, black currant, ecchium, fish, plankton extract, capryloyl glycine, Seppicalm VG (sodium palmitoylproline and nymphea alba) from Seppic, a Pygeum extract, Boswellia serrata extract, Centipeda cunnighami extract, Helianthus annuus extract, Linum usitatissimum extract, mint extract, rose extract (including Rosa Gallica), tocotrienols, extracts of Cola nitida, piperonal, a clove extract, an extract of Epilobium Angustifolium, aloe vera, an extract of Bacopa moniera, phytosterols, cortisone, hydrocortisone, indomethacin and beta methasone.

  The organic photoprotective agents are in particular chosen from anthranilates; cinnamic derivatives; dibenzoylmethane derivatives; salicylic derivatives, camphor derivatives; triazine derivatives such as those described in patent applications US 4367390, EP863145, EP517104, EP570838, EP796851, EP775698, EP878469, EP933376, EP507691, EP507692, EP790243, EP944624; benzophenone derivatives; 13,13-diphenylacrylate derivatives; benzotriazole derivatives; benzalmalonate derivatives; benzimidazole derivatives; imidazolines; bis-benzoazolyl derivatives as described in patents EP669323 and US 2,463,264; p-aminobenzoic acid derivatives (PABA); methylene bis (hydroxyphenyl benzotriazole) derivatives as described in US5,237,071, US5,166,355, GB2303549, DE 197 26 184 and EP893119; and filter polymers and silicone filters such as those described in particular in the application WO-93/04665; dimers derived from α-alkylstyrene such as those described in patent application DE19855649.

  The inorganic photoprotective agents are chosen from pigments or even nanopigments (average size of the primary particles: generally between 5 nm and 100 nm, preferably between 10 nm and 50 nm) of coated or uncoated metal oxides such as, for example, nanopigments titanium oxide (amorphous or crystallized in rutile and / or anatase form), iron, zinc, zirconium or cerium which are all UV photoprotective agents well known per se. Conventional coating agents are, moreover, alumina and / or aluminum stearate. Such nanopigments of metal oxides, coated or uncoated, are in particular described in patent applications EP518772 and EP518773.

  The photoprotective agents are generally present in the composition according to the invention in proportions ranging from 0.1 to 20% by weight relative to the total weight of the composition, and preferably ranging from 0.2 to 15% by weight. relative to the total weight of the composition.

  The following examples illustrate the invention. Example 1

  Measurement of the modulating effect of the melanogenesis of the styrene / maleic anhydride copolymer (50/50) hydrolyzed in the form of the 40% sodium salt in water (SMA1000HNa by the company CRAY VALLEY), in the presence or in the presence thereof absence of ascorbic acid, on co-culture of normal human keratinocytes and melanocytes

  1.1. MATERIAL AND METHOD The modulatory effect on melanogenesis of the SMA1000HN copolymer was tested according to the method described in patent FR-A-2 734 825, as well as in the article by R. Schmidt, P. Krien and M. Régnier, Anal. . Biochem., 235 (2), 113-18, 1996. Briefly, the method comprises the steps of:

  To co-culture normal human keratinocytes / melanocytes in a medium containing the tested extract as well as a melanin precursor labeled, in this case, C14-labeled thiouracil; to lyse cells containing melanin with protein degrading enzymes; passing the resulting extract through an anion exchange filter having a pore diameter of less than or equal to 1 m, and evaluating the amount of melanin fixed by the filter by means of a radioactive do-sage of thiouracil.

  Specifically, 50,000 normal human keratinocytes and 17,000 normal human melanocytes are mixed and seeded per well of 96 well plates (Costar type) and cultured for three days in the differentiation medium. For the next three days, the culture medium is replaced daily by the defined test medium (containing the products to be evaluated, as well as 3 Ci / ml of C14-labeled thiouracil). The following controls are carried out: control culture: test medium positive melanogenesis stimulation control: test medium + 1 mM ty-rosine; 3 positive melanogenesis inhibition controls: test medium + 500 M of kojic acid, respectively; 100 μM arbutin; 10% M lucinol (2-butyl benzene 1,3-diol).

  The total radioactivity incorporated in the proteins is estimated by the incorporation of tritiated leucine, taken as an indicator of proliferation and early indicator of cytotoxicity. The day before taking, 1 Ci / ml of tritiated leucine is added to the test medium. It is considered that a product is cytotoxic when the tritiated leucine content decreases by at least 30%.

  After one night, the cells are rinsed in phosphate buffer (Phosphate Buffered Saline, PBS). Proteins are precipitated with 5% trichloroacetic acid (TCA) and washed to remove free radioactivity. The proteins are incubated overnight at 37 ° C with a 20 μl / ml Proteinase K solution in Tris-HCl Triton-EDTA buffer.

  50 μl of total extract are removed and transferred to a 96-well plate (Wallac) and 150 μl of scintillant liquid (Optiphase Supermix) are added. The remainder of the extract, 950 μl, is filtered through a DEAE Filtermat filter. After rinsing, the Meltilex solid scintillant-coated filter is transferred to a counting plate. The radioactivity is counted using the Wallac meter. The results are expressed as a percentage of the control according to the formula:

  (14CP / 3HP) - (14CT / 3HT) X 100 (14CT / 3HT)

  wherein: 14CP is the average of 14C thiouracil decays per minute (dpm) over 3 similar wells treated with a product (P); 3HP is the average of the corresponding 3H leucine dpm; 14CT is the average of 14C C-thiouracil dpm on 3 wells

  3HT is the average of the corresponding 3H leucine dpm. The ratio of thiouracil incorporation to leucine incorporation is calculated to normalize melanogenesis to the amount of protein present in the well. This ratio reflects the modulation of melanogenesis. 5 .2. RESULTS References 3H Leu. 14C ThioU. 14C ThioU. (% / Control) (% / Control) 3H Leu. Tyrosine 1 mM + 6% 96% 85% Kojic Acid 500 M -8% -56% -52% Arbutin 100 M -8% -49% -44% Lucinol 10 M 4% -60% -62% 3H Leu. 0/0 -17% -23% -23% (% / Control) 14C ThioU. -14% -69% -79% -76% (% / Control) 14C ThioU. -14% -62% -72% -68% 3H Leu. copolymer 18 53 70 105 SMA] (M) 3H Leu. -4 / 0 -15% -12% -11% (% / Control) 14C ThioU. -28% -66% -67% -71% (% / Control) 14C ThioU. -25% -60% -63% -68% 3H Leu. [copolymer 18 53 70 105 SMA] (MW) 3H Leu. 2% 4% 0% -16% (% / Control) 14c ThioU. -21% -42% -56% -62% (% / Warning) 14c ThioU. -23% -45% -56% -54% 3H Leu. 0.23 mM Vitamin C I C50 0.23 mM Vitamin C + 42 M SMA I C50 60 M SMA In the tables, SMA stands for the copolymer SMA1000HNa 1.3. CONCLUSIONS No cytotoxicity of the tested products was observed at the doses evaluated. Vitamin C exhibits depigmenting activity and achieves IC50 on this model at about 0.23 mM. The activity of vitamin C is not modified in the presence of the SMA1000HNa8 copolymer. On the other hand, the SMA1000HNa copolymer tested alone, in the same concentration range as in the presence of vitamin C, also has a depigmenting potential with a dose effect. It makes it possible to reach the IC50 at 60 M of copolymer. The SMA1000HNa copolymer therefore has a depigmenting activity which is peculiar to it. The activities of vitamin C and SMA1000HNa copolymer are not synergistic. The activity of the copolymer SMA1000HNa seems on the contrary to be masked in the presence of vitamin C.

  Example 2: 2) Principle of the anti-pigmentation protocol: Measurement of the modulatory effect of the photoinduced melanogenesis of the SMA1000HNa polymer in the presence or in the absence of ascorbic acid on co-culture of normal human keratinocytes and melanocytes (anti-aging effect). pigmentation) 25 2.1. MATERIAL AND METHOD Normal human melanocyte / keratinocyte co-cultures (NHM / NHK) are irradiated with UV radiation, repeated daily for 4 days, in the presence or absence of the products to be evaluated. The synthesis of melanin is quantified as previously through the incorporation of 14 thiouracil present in the culture medium. In parallel, a protein assay is performed in each well in order to normalize the melanic synthesis and to estimate the toxicity of the product. An attenuation of the induction of melanogenesis after UV irradiation can thus be demonstrated. More specifically, the melanocytes and keratinocytes are inoculated respectively to 80000 and 250000 cells per well in a 24-well plate in the keratinocyte differentiation medium. The plates are incubated for 3 days at 37 ° C. before treatment.

  To avoid photo oxidation of one of its components, the culture medium is replaced at the time of irradiation with a solution of the products in PBS. The products are brought into contact with the cells 15 minutes before irradiation. UV irradiation is performed using a solar simulator. The dose delivered is 7J / cm2. Irradiation source: Oriel Xenon simulator 1000W + dichroic filter + WG 320 / 1.5 mm.

  The following controls are carried out: Non-irradiated control (quantification of constitutive melanogenesis) Irradiation control control 2 Positive inhibition controls for photoinduced melanogenesis: (100 μM Arbutin, 1 M Lucinol) After irradiation, PBS is removed and the cells are incubated in a semi-defined culture medium to which the products are added and 14C-thiouracil (1 Ci / ml). This treatment is renewed daily for 4 days.

  For each experimental condition, cell lysates are made by rinsing the cells with phosphate buffer (PBS). Proteins are precipitated with 5% trichloroacetic acid (TCA) and washed to remove free radioactivity. The proteins are incubated for one week end at 37 [deg.] C. with a solution of Proteinase K at 20 μl / ml in Tris-HCl-triton-EDTA buffer. 5 μl of total extract are removed and transferred to a 96-well plate (Wallac). The proteins are assayed using the Protein Assay Reagent (Pierce) assay kit. The amount of protein per well (P) will be used to normalize melanogenesis. The rest of the extract is filtered on DEAE Filtermat filter (Wallac). After rinsing, the Meltilex solid scintillant-covered filter (Wallac) is transferred to a costar counting plate. The radioactivity is counted using the Wallac counter and allows the quantification of melanogenesis (M) by measuring the 14C-thiouracil (ccpm) incorporated by the cells. Standardized melanogenesis (MN) = M / P Melanogenesis Photo Induced (MPI) = MN (irradiated sample) ù MN (non-irradiated sample) Anti-pigmenting Product Effect (%) = [[MPI (irradiated sample + treated) -MPI (irradiated specimen)] / MPI (irradiated specimen) X 100 2-2 RESULTS References MPI Proteins Anti-effect (% / Control (% / non-irradiated pigment of non-irradiated) non-irradiated) Product Control SSR -21% 225% - Arbutin 100 M + SSR -15% -24% -111% Lucinol 1 M + SSR -14% -36% - 116% Protein -12% -19% -19% -22% (% / Non-irradiated indicator) MPI 134% 78% 23% 0/0 (% / non-irradiated control) Anti-40% -65% -90% -100% pigmenting effect 0.47 mM vitamin C [SMA] 53 180 350 530 (PM) Protein -24% -26% -25% -27% (% / non-irradiated control) MPI 118% 69% 17% 5/0 (% / non-irradiated control) Anti-47% -69% -92% -102% pigmenting effect product I C50 0. 37 mM vitamin C + 67 PM SMA [SMA] 53 180 350 530 (PM) Protein -24% -23% -22% -20% (% / non-irradiated control) MPI 189% 1 26% 160% 166% (% / non-irradiated control) Anti--44% -29% -26% pigmenting effect of the product 2.3. CONCLUSIONS No cytotoxicity of the tested products was observed at the doses evaluated. Vitamin C exhibits anti-pigmenting activity and achieves IC50 on this model at about 0.47 mM. The activity of vitamin C at low concentrations under UV is substantially improved in the presence of the SMA1000HNa copolymer. Indeed, the IC 50 of vitamin C is reached at 0.37 mM in the presence of the copolymer SMA1000HNa, faster than when it is tested alone. This slight improvement could be due to the stabilizing potential of the SMA1000HNa copolymer on vitamin C, under these pro-oxidative experimental conditions of exposure to UV rays. Nevertheless, the SMA1000HNa copolymer tested alone, in the same concentration range as in the presence of vitamin C, also has its own anti-pigmenting potential. This effect is not synergistic with that of vitamin C.

  EXAMPLE 3 A depigmenting gel for the body having the following composition is prepared: 0/0 by weight Xanthan gum 0.4 potassium hydroxide 0.3 Dimethicone PEG-7 phosphate (PECOSIL PS 100 2 from Phoenix Chemical) styrene / maleic acid copolymer, sodium salt 1 to 40% by weight in water (SMA 1000HNa from I C50 Not reached Cray Valley) Cyclohexasiloxane Ethanol Water 70.65 Acrylic thickening polymer (Carbomer) 0.4 Acrylic acid / methacrylate copolymer of 0.25-methyl in a ethyl acetate / cyclohexane mixture (Pemulen TRI from Noveon) The composition applied to the skin with pigmentation spots makes it possible, after several applications, to fade stains. Example 4

  A depigmenting tonic for the face having the following composition is prepared: 0/0 by weight Triethanolamine 0.6 Disodium salt of ethylene dithophene tetracetic copolymer styrene / maleic acid, salt 1 sodium 40% by weight in water (Cray Valley SMA 1000HNa) Cyclopentasiloxane 2 Dimethicone 2 Ethanol 10 Water 82.8 Preservatives 0.90 Copolymer acrylic acid 0.5 stearyl methacrylate in a mixture of ethyl acetate / cyclohexane (Pemulen TRI from Noveon) composition applied on a few with pigmentation spots allows after several applications to fade stains. Example 5

  A depigmenting facial lotion having the following composition is prepared: Butylene glycol PEG-32 0.5 PEG-8 1.5 Styrene / maleic acid copolymer, 1 sodium salt 40% by weight in water (SMA 1000HNa from Cray Valley) Glycerin 3 Propylene Glycol 0.25 PEG-60 po- 0.17 lyoxyethylenated hydrogenated castor oil (60 0E) Disodium salt of ethylene dia- 0.08 tetracetic acid Water 88.65 Preservatives 0.85 Example 6: A facial care is prepared having the following composition: 0/0 by weight Disodium salt of ethylene dia- 0.05 tetracetic acid Dimethicone / vinyl dimethicone croo-1.2 spolymer (KSG 16 from Shin Tetsu) Nylon -12 5 styrene / maleic acid copolymer, salt 1 40% by weight sodium in water (Cray Valley SMA 1000HNa) Cyclopentasiloxane 17.3 Glycerine 23 Propylene glycol 6 Dimethicone 3.8 PEG / PPG-18/18 dimethicone (DC 5225 2.4 C from Dow Corning) apricot 3 16 10 Phenyl trimethicone (DC 556 from at 4 Dow Corning) Silica 3 Water 29.95 Preservatives 0.3 Applied daily, the composition blurs facial patches. Example 7

  A facial and hand cream having the following composition is prepared: 0/0 by weight Myristyl alcohol 0.025 stearyl alcohol 1.025 Phenoxyethanol 0.8 potassium hydroxide 0.5 glyceryl stearate 1.25 cetyl alcohol 0.95 styrene / maleic acid copolymer, salt 1 of sodium at 40% by weight in water (SMA 1000HNa from Cray Valley) Cyclopentasiloxane Hydrogenated polyisobutene glycerin (Paralmer oil) Water 65.10 Acrylic thickening polymer (Car- 0. 6 bomer) stearate PEG-50 2.5 PEG-100 Stearate 1.25 The composition applied to the skin blurs stains.

Claims (16)

  1. Use as an agent for depigmenting and / or bleaching the skin, in particular for eliminating pigment spots, senescence spots and / or as an anti-pigmenting agent, of a copolymer of styrene monomer and unsaturated dicarboxylic acid ethylenically.   2. Use according to the preceding claim, characterized in that the styrenic monomer is selected from styrene and alpha-methyl styrene.   3. Use according to claim 1 or 2, characterized in that the styrenic monomer is styrene.   4. Use according to any one of the preceding claims, characterized in that the ethylenically unsaturated dicarboxylic acid is selected from maleic acid, itaconic acid, or their hydrolysed anhydride derivative after polymerization.   5. Use according to any one of the preceding claims, characterized in that the ethylenically unsaturated dicarboxylic acid is chosen from maleic acid, or their hydrolysed anhydride derivative after polymerization.   6. Use according to any one of the preceding claims, characterized in that said copolymer is in salt form.   7. Use according to the preceding claim, characterized in that said copolymer is in salt form selected from ammonium, sodium, potassium, lithium, and preferably in the form of sodium salt. 30   8. Use according to any one of the preceding claims, characterized in that said copolymer has a mole fraction in ethylenically unsaturated dicarboxylic acid unit of between 0.1 and 0.9, and preferably between 0.4 and 0, 9. 35   9. Use according to any one of the preceding claims, characterized in that said copolymer has a weight average molecular weight of between 1000 and 500 000, and preferably between 1000 and 50 000.   10. Use according to any one of the preceding claims, caractéri-40 sée in that said copolymer has a solubility in water at 25 C greater than or equal to 2 g / l. 25   11. Use according to any one of the preceding claims, characterized in that said copolymer is a copolymer of styrene and maleic acid.   12. A cosmetic process for depigmenting and / or lightening skin with pigmentation spots comprising applying to the skin a composition comprising, in a physiologically acceptable medium, at least one copolymer of styrene monomer and ethylenically unsaturated dicarboxylic acid according to any preceding claim, the composition being free of hydrophilic active ingredient sensitive to oxidation.   13. Method according to the preceding claim, characterized in that it is intended to eliminate brownish pigment spots and / or senescence spots, and / or to lighten the burnished skin.   14. Method according to one of claims 12 or 13, characterized in that the copolymer is present in a content ranging from 0.1% to 40% by weight, relative to the total weight of the composition, and more particularly in a content ranging from 0.1 to 20% by weight, relative to the total weight of the composition.   15. Process according to any one of Claims 12 to 14, characterized in that it comprises at least one ingredient chosen from desquamating agents, soothing agents, organic photoprotective agents and mineral photoprotective agents.   16. Use of a copolymer of styrene monomer and ethylenically unsaturated dicarboxylic acid according to any one of claims 1 to 11 for the manufacture of a dermatological composition for depigmenting and / or whitening the skin.