FR2902320A1 - Cosmetic use of butylated hydroxyanisole to prevent, limit and/or stop the development of canities - Google Patents

Abstract

Cosmetic use of butylated hydroxyanisole (I) to prevent, limit and/or stop the development of canities. Independent claims are included for: (1) a cosmetic composition comprising (I) in combination with another active agents that controls desquamating scalp and/or herbal extracts having propigmentante activity, in a medium; (2) a composition comprising (I) in combination with an agent slowing hair loss or promoting their regrowth; and (3) treatment of canities, comprises oral administration or topical application (on the zone to be treated) of a composition comprising (I). ACTIVITY : Dermatological; Endocrine-Gen. MECHANISM OF ACTION : Glutathione synthesis stimulator.

Description

The present invention relates to the cosmetic use of butylated

  hydroxyanisole to treat canities.

  The hair follicle is a tubular invagination of the epidermis that penetrates to the deep layers of the dermis. The lower part, or hairy bulb, itself contains an intussusception in which is the dermal papilla. The lower part of the bulb is a zone of cellular proliferation where the precursors of the keratinized cells constituting the hair are found. Ascending cells from these precursors keratinize progressively in the upper part of the bulb, and this set of keratinized cells will form the hair shaft.

  The color of hair and hair is based in particular on the presence in quantities and variable ratios of two groups of melanins: eumelanins (brown and black pigments) and pheomelanines (red and yellow pigments). The pigmentation of hair and hair requires the presence of melanocytes in the bulb of the hair follicle. These melanocytes are in an active state, i.e. they synthesize melanins. These pigments are transmitted to the keratinocytes intended to form the hair shaft which will lead to the growth of a pigmented hair or hair. This structure is hereinafter called follicular unit of pigmentation.

  In mammals, melanogenesis involves at least three enzymes: tyrosinase, DOPAchrome tautomerase (TRP-2, for Tyrosinase Related Protein 2) and DHICAoxidase (TRP-1, for Tyrosinase Related Protein 1). Tyrosinase is the enzyme that initiates the biosynthesis of melanins. It is also described as the limiting enzyme of melanogenesis.

  TRP-2 catalyzes the tautomerization of DOPAchrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA). In the absence of TRP-2, DOPAchrome undergoes spontaneous decarboxylation to form 5,6-dihydroxyindole (DHI). DHICA and DHI are both precursors of pigments, TRP-1 oxidizes DHICA molecules to form quinone derivatives (Pawelek JM and Chakraborty AK.) The erizymology of melanogenesis In: Nordlund JJ, Boissy RE, Hearing VJ, King RA , Ortonne JP, The Pigmentary System: Physiology, arid pathophysiology, New York: Oxford University Press, 1998, pp. 391-400).

  The three enzymes, tyrosinase, TRP-2 and TIRP-1, appear specifically involved in melanogenesis. In addition, the activity of these three enzymes has been described as necessary for maximal activity of eumelanin biosynthesis.

  Hair and hair undergo a cycle. This cycle comprises a growth phase (anagen phase), a degeneration phase (catagen phase) and a rest phase (telogen phase) following which a new anagen phase will develop. Because of this hair cycle, and unlike the epidermal pigmentation unit, the follicular unit of pigmentation must also be cyclically renewed.

  Canitia (natural whitening of the hair) is related to a specific and progressive thinning of the hair melanocytes affecting both the hair bulb melanocytes and the precursor cells of melanocytes (Commo et al., Br J Dermatol 2004; 150: 435-443 ). Other cell types present in hair follicles are unaffected. In addition, this rarefaction of melanocytes is not observed in the epidermis. The cause of this progressive and specific rarefaction of melanocytes and precursors of melanocytes in the hair follicle is not yet identified.

  It therefore seems necessary to combat the disappearance of melanocytes from human hair follicles, a process that affects both the active melanocytes of the bulbs and the quiescent melanocytes of the upper region of the hair follicles, to fight against canitism.

  The Applicant has identified a means of combating hair whitening by acting on the TRP-2 enzyme (WO 03/103568), in particular by increasing the level of GSH. Indeed, it has shown that the expression of the TRP-2 enzyme is correlated with a higher level of GSH in melanocytes, the expression of TRP-2 induces an increase in the level of GSH in melanocytes. Thus in melanocytes that do not express TRP-2 (for example, hair melanocyte precursors), there is a low GSH level compared to melanocytes that express the TRP-2 enzyme (for example, all melanocytes of the skin). The Applicant has therefore identified a new target for the treatment of canities, more particularly, it has shown that compounds capable of increasing the level of GSH in TRP-2 deficient melanocytes increase the viability of these melanocytes,

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  reduce hair whitening and lead, contrary to their depigmenting effect described in the literature, to the restoration of hair pigmentation (F R04 / 13756).

  The Applicant has now demonstrated that butylated hydroxyanisole (also designated 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole): OH by its ability to increase the level of GSH in melanocytes, opposes bleaching of the hair, and leads to the restoration of pigmentation of the hair.

  Thus the object of the present invention relates to the use of butylated hydroxyanisole as an agent for preventing, limiting or stopping the progression of canities, and maintaining and / or promoting the natural re-pigmentation of hair and / or hair . In particular, the object of the invention relates to the use of butylated hydroxyanisole to prevent and / or limit and / or stop the development of canities.

  The object of the invention also relates to the use of butylated hydroxyanisole to maintain the natural pigmentation of hair and / or gray hairs.

  The subject of the invention is also a composition for combating canities, comprising, in a cosmetically acceptable medium, butylated hydroxyanisole combined with another hair active selected from desquamating agents of the scalp and / or extracts. plants with pro-pigmenting activity. The present invention also relates to a composition for combating canitia comprising in a cosmetically acceptable medium, butylated hydroxyanisole associated with an agent slowing hair loss or promoting their regrowth.

  The composition according to the invention comprises an amount of butylated hydroxyanisole of between 0.001 and 10% by weight relative to the total weight of the composition, preferably between 0.01 and 5% by weight relative to the total weight of the composition and even more preferably between 0.1 and 1% by weight relative to the total weight of the composition.

  The composition according to the invention may be administered orally or applied topically to the skin (on any cutaneous area of the body covered with hair) and / or the scalp.

  Orally, the composition according to the invention may contain butylated hydroxyanisole in solution in a food liquid such as an aqueous or aqueous-alcoholic solution, optionally flavored. They can also be incorporated in an unmanageable solid carrier and be for example in the form of granules, pills, tablets or dragees. They can also be placed in solution in a food liquid conditioned itself possibly in unmanageable capsules.

  Depending on the mode of administration, the composition of the invention may be in any galenical form normally used, particularly in cosmetology. A preferred composition of the invention is a cosmetic composition suitable for topical application to the scalp and / or the skin.

  For topical application, the composition that may be used according to the invention may especially be in the form of an aqueous, aqueous-alcoholic or oily solution or of the lotion-type or serum-type dispersion, of emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersion of a fatty phase in an aqueous phase (O / W) or conversely (W / O), or suspensions or emulsions of soft consistency of the cream or gel type, aqueous or anhydrous, or else microcapsules or microparticles, or vesicular dispersions of ionic and / or nonionic type. It can thus be in the form of ointment, tincture, cream, ointment, powder, patch, impregnated buffer, solution, emulsion or vesicular dispersion, lotion, gel, spray, suspension, shampoo, aerosol or foam. They can be anhydrous or aqueous. It can also consist of solid preparations constituting soaps or cleaning rolls. These compositions are prepared according to the usual methods.

  The composition that may be used according to the invention may in particular be a composition for hair care, and in particular a shampoo, a setting lotion, a treatment lotion, a cream or a styling gel, a dyeing composition (especially dyes). xydation) optionally in the form of coloring shampoos, restructuring lotions for hair, mask

  The cosmetic composition according to the invention will preferably be a cream, a hair lotion, a shampoo or a conditioner. The amounts of the various constituents of the compositions that can be used according to the invention are those conventionally used in the fields under consideration.

  When the composition usable according to the invention is an emulsion, the proportion of the fatty phase may 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, the waxes, the emulsifiers and the coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the cosmetics field. The emulsifier and the co-emulsifier 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. composition. The emulsion may further contain lipid vesicles.

  When the composition that can be used according to the invention is an oily solution or gel, the fatty phase may represent more than 90% of the total weight of the composition. In one variant of the invention, the composition will be such that the butylated hydroxyanisole is encapsulated in a coating such as microspheres, nanospheres, oleosomes or nanocapsules. This type of formulation is advantageous because it makes it possible to specifically target the hair follicle and thus the release of the active agent at its site of action.

  By way of example, the microspheres may be prepared according to the method described in the patent application EP 0 375 520.

  The nanospheres may be in the form of an aqueous suspension and be prepared according to the methods described in patent applications FR 0015686 and FR 0101438. The oleosomes consist of an oil-in-water emulsion formed by oily globules provided with a lamellar liquid crystal coating dispersed in an aqueous phase (see patent applications EP 0 641 557 and EP 0 705 593).

  Butylated hydroxyanisole may also be encapsulated in nanocapsules consisting of a lamellar coating obtained from a silicone surfactant (see patent application EP 0 780 115), the nanocapsules may also be prepared based on water-dispersible sulfonic polyesters (see patent application FR 0113337).

  Butylated hydroxyanisole may also be complexed on the surface of cationic oily globules, whatever their size (see patent applications EP 1 010 413, EP 1 010 414, EP 1 010 415, EP 1 010 416, EP 1 013 338). , EP 1 016 453, EP 1 018 363, EP 1 020 219, EP 1 025 898, EP 1 120 101, EP 1 120 102, EP 1 129 684, EP 1 160 005 and EP 1 172 077). Butylated hydroxyanisole can finally be complexed on the surface of nanocapsules or nanoparticles provided with a lamellar coating (see EP 0 447 318 and EP 0 557 489) and containing a cationic surfactant on the surface (see references cited previously for cationic surfactants). In particular, a composition such as the coating containing butylated hydroxyanisole with a diameter of less than or equal to 10 μm will be preferred. When the coating does not form a spherical vesicle, diameter is understood to mean the largest dimension of the vesicle. In a known manner, the composition according to the invention may also contain adjuvants which are customary in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters, odor absorbers and dyestuffs. The amounts of these various adjuvants are those conventionally used in the cosmetics field, and for example from 0.01% to 10% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into the lipid spherules.

  The compositions that may be used according to the invention may combine butylated hydroxyanisole with other active agents. Among these active agents, there may be mentioned by way of example: agents that modulate the differentiation and / or proliferation and / or pigmentation of skin cells such as retinol and its esters, vitamin D and its derivatives, estrogens such as estradiol, cAMP modulators such as POMC derivatives, adenosine, or forskolin and its derivatives, prostaglandins and their derivatives, triiodotrionine and its derivatives; extracts of plants such as Iridaceae or soybean extracts, which may then contain isoflavones or not; extracts of microorganisms; anti-free radical agents such as α-tocopherol or its esters, superoxide dismutases or its mimetics, certain metal chelators or ascorbic acid and its esters; anti-seborrheic agents such as certain sulfur amino acids, retinoic acid, cyproterone acetate; other desquamating agents of the scalp such as zinc pyrithione, selenium disulfide, climbazole, undecylenic acid, ketoconazole, piroctone olamine (octopirox) or ciclopirocton (ciclopirox); in particular, it may be active stimulating regrowth and / or promoting the slowing down of hair loss, it may more particularly be mentioned without limitation: - nicotinic acid esters, including tocopherol nicotinate nicotinate benzyl nicotinate and C1-C6 alkyl nicotinates such as methyl or hexyl nicotinates; pyrimidine derivatives, such as 2,4-diamino-6-piperidinopyrimidine 3-oxide or "Minoxidil" described in US Pat. Nos. 4,139,619 and 4,596,812; Aminexil or 2,4-diarnino pyrimidine oxide described in WO96 / 09048; the lipoxygenase or cyclooxidase inducing agents which promote hair regrowth, such as those described by the Applicant in the European patent application EP 0 648 488; antibacterial agents such as macrolides, pyranosides and tetracyclines, and in particular Erythromycin; calcium antagonists, such as Cinnarizine, Nimodipine and Nifedipine; hormones, such as estriol or analogues, or thyroxine and its salts; antiandrogenic agents, such as oxendolone, spironolactone, diethylstilbestrol and flutamide; steroidal or nonsteroidal inhibitors of 5-a-reductases such as those described by the Applicant in European Patent Applications EP 0 964 852 and EP 1 068 858 or else finasteride; ATP-dependent potassium channel agonists such as cromakalim and nicorandil; plant extracts with pro-pigmenting activity such as chrysanthemum extracts as described in FR 2768343 and extracts of Sanguisorba described in FR 2782920.

  Preferably, the butylated hydroxyanisole is associated with at least one other hair active agent chosen from the desquamative states of the scalp, agents which slow hair loss or promote their regrowth, plant extracts with propigmenting activity.

  Another object of the present invention relates to a method of cosmetic treatment of canities, characterized in that a composition as defined above comprising butylated hydroxyanisole is administered or applied to the zone to be treated.

  The invention also relates to a cosmetic treatment method intended to maintain the natural pigmentation of hair and / or gray or white hairs, characterized in that a composition such as is administered or applied to the area to be treated. defined above including butylated hydroxyanisole.

  The methods of treating canities and pigmentation of hair and / or gray or white hairs may also consist in the ingestion of a composition comprising at least butylated hydroxyanisole.

  The areas to be treated may be, for example and without any limitation, the scalp, the eyebrows, the mustache and / or the beard and any area of the skin covered with hair.

  More particularly, the methods of cosmetic treatment of canities and natural pigmentation of gray and white hair and / or hair consist in applying a composition comprising butylated hydroxyanisole.

  Cosmetic treatment methods for combating canities and / or for maintaining the natural pigmentation of hair and / or gray or white hairs may for example consist in applying the composition to the hair and the scalp, in the evening, keeping the composition all night and possibly shampoo in the morning or wash the hair with this composition and leave it in contact for a few minutes before rinsing. The composition according to the invention has proved particularly advantageous when it is applied in the form of a hair lotion, optionally rinsed or even in the form of a shampoo.

  EXAMPLE 1 Demonstration of the Protection of TRP-2 (-) Melanocytes by the Compounds of the Invention The principle of this test is the following: a-cultivation of two cell types expressing TRP-2 and expressing not TRP-2, respectively Cell-TRP2 (+) and Cell-TRP2 (-), preferably the cells are melanocytes; b) Celll-TRP2 (-) cells of the test compound are added to the culture medium; c) incubating the cultures for a time long enough to allow the increase of the level of GSH in the cells; d-exposure of cells to a condition inducing cell death or senescence; e- measure of cell death or senescence.

  In this case, the ability of butylated hydroxyanisole to compensate for the weak expression of TRP-2 in the wild-type WM35 line was measured by protecting this cell line when these cells are exposed to H2O2 stress. The effect of these compounds can also be measured on melanocytes in a surviving bulb or on TRP-2 (+) vs (-) cells obtained from normal human melanocytes.

  The study was performed using the WM35 human melanocyte line, which expresses TRP-2 very weakly (Pak BJ et al., Melanoma Res., 2000: 10: 499), called the wild-type line in the study and a cell line derived from the WM35 line that strongly expresses TRP-2 called clone-2 in the study, obtained by transfection of an expression vector encoding TRP-2. For carrying out the test, the cells are seeded at a density of 2.5 × 10 -4 cells / well then treated with butylated hydroxyanisole at concentrations of between 1 and 100 nm.

  After 24h cells are exposed to H2O2-induced stress. Cell viability is measured 24 hours after stress using Alamar blue (UP669413, Uptima, Interchim). EXAMPLE 2 Composition - butylated hydroxyanisole treating shampoo 1.5 g Polyglyceryl 3-hydroxylarylether 26 g Hydroxypropyl cellulose sold under the name 2 g Klucell G by the company Hercules Preservatives qs ethanol 95 50 g Water qs 100 g20 This shampoo is used in each wash with a laying time of about one minute. Prolonged use, of the order of two months, leads to the slowing down of canities and the gradual repigmentation of gray hair. This shampoo may also be used as a preventive measure to delay bleaching.

Claims (8)

  1. Cosmetic use of butylated hydroxyanisole to prevent and / or limit and / or stop the development of canities.   2. Use according to claim 1 for maintaining and / or restoring the natural pigmentation of hair and / or gray hairs.   3. Use according to claim 1 or 2, characterized in that said compound is administered topically or orally.   4. Cosmetic composition comprising, in a cosmetically acceptable medium, butylated hydroxyanisole combined with another active agent chosen from desquamating agents of the scalp and / or plant extracts with propigmenting activity.   5. Cosmetic composition comprising in a cosmetically acceptable medium butylated hydroxyanisole associated with an agent slowing hair loss or promoting their regrowth. 20   6. Composition according to claim 4 or 5, characterized in that said compound is encapsulated in a coating such as microspheres, nanospheres, oleosomes or nanocapsules.   7. Composition according to any one of claims 4 to 6, characterized in that it is suitable for topical application to the scalp and / or areas of the skin covered with hair.   8. Process for the cosmetic treatment of canities, characterized in that a composition comprising butylated hydroxyanisole is administered orally or applied topically to the area to be treated. 15