FR2825923A1 - Use of copper diisopropyl salicylate for inhibiting nitric oxide synthase for preventing and treating dermal ageing, irritation, sensitivity, inflammation, erythema, hypermelanosis, rosacea, sweating and hair loss - Google Patents

Abstract

The use of copper diisopropyl salicylate (CuDIPS) is claimed in a composition used to inhibit nitric oxide synthase.

Description

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The present invention relates to the use of an effective amount of copper diisopropyl salicylate (CuDIPS), in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to inhibit the NO-synthase.

The term NO-synthase covers a family of enzymes that enzymatically convert l-arginine to citrulline, a reaction in which a multifunctional gas mediator, nitrogen monoxide or no.

NO-synthases exist in three forms, two constitutive forms, nomenclature grouping the neuronal NO-synthase (or NOS 1) and the endothelial NO-synthase (or NOS 3), and the inducible form (or NOS 2) (Medicine / Sciences 1992.8, pp. 843-845).

It is also understood in the text that without indication to the contrary the term NO-synthase covers all the isoforms of the enzyme.

Thus, according to the invention, the term NO-synthase inhibitors means any product which ultimately leads, notwithstanding the isoform of NO synthase, to the decrease of the concentration of NO. By way of example, mention may be made of products which reduce the amount of active NO-synthase, which block the enzymatic activity of the NO synthase or its induction or which inhibit the activity of the product.

Nitric oxide has an extra electron structure that makes it extremely chemically reactive. It is well known that such compounds are harmful and we try to limit their production as much as possible. Thus, in the case of nitric oxide, NO-synthase inhibitors have been widely studied.

NO is a multifunctional signal molecule active in a wide variety of body systems and tissues. In addition to its damaging effects on the cells linked to its hyper-reactivity due to its structure comprising an additional electron, it is recognized inter alia as intervening particularly in the cardiovascular system (regulator of the blood pressure with vasodilator effect, inhibitor of the platelet aggregation with effect anticoagulant), in the nervous system (memory, modulation of the release of neurotransmitters), in the immunological system (modulation of immune defenses, inflammation, involvement in autoimmune diseases).

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immunes).

immune).

It is now well accepted that NO plays a prominent role in the skin.

The NO can be synthesized by all the varieties of cells constituting the skin and as such it intervenes in multiple and complex processes of regulation such as the regulation of the differentiation and / or the cellular proliferation, the vasodilatation, the melanogenesis , the response to environmental variations (homeostasis).

Its involvement in differentiation and cell proliferation (stimulatory effect), particularly keratinocytes, combines it with epidermal growth and healing as well as hyperproliferative disorders (psoriasis).

Due to its electronic hyperreactivity that can lead to cell degradation or destruction, NO is involved in apoptotic processes and in the intrinsic and / or extrinsic aging of the skin.

It is involved in immunological and inflammatory skin processes. It is indeed commonly accepted that NO plays a role in contact hypersensitivity reactions, in cutaneous allergic manifestations, in the immune response of the skin. Similarly, in addition to its direct proinflammatory role, it is the mediator between neuropeptides such as substance P and / or the calcitonin gene related peptide (CGRP) in cutaneous neurogenic inflammatory processes, hence its involvement in so-called sensitive skin phenomena.

NO is also involved in reducing the barrier effect of the skin, as well as in reducing cutaneous hydration.

The involvement of NO in vasodilatation is associated with erythema of the skin, particularly erythema induced by ultraviolet radiation, localized or diffuse erythematous rashes of the skin such as those caused by drugs, toxins and / or viral or bacterial infections, with rosacea.

NO is recognized as an intermediate in the melanogenesis induced by ultraviolet radiation type B (UVB). It is also one of the factors involved in disorders of the hypermelanosis type.

Finally, the NO seems involved in the control of sweating as well as in hair loss.

We therefore understand the interest that exists to have inhibitors of NO-synthases.

In this respect, numerous inhibitors have already been proposed in the prior art.

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On peut citer plus particulièrement la N9-monométhyl-L-arginine (NMMA), l'ester méthylé de la N9-nitro-L-arginine (NAME), la N9-nitro-l-arginine (NNA), la N9amino-t-arginine (NAA), la N9'N9-diméthyl-arginine (la diméthylarginine asymétrique, dénommée ADMA), le chlorure de diphénylèneiodonium, le 2- (4-carboxyphényl) -4, 4,5, 5-tetraméthylimidazoline-1-oxy-3-oxyde, la 7-nitroindazole, la N (5)- (1-iminoéthyl)-L-ornithine, l'aminoguanidine, la canavanine et l'ebselen.

N9-monomethyl-L-arginine (NMMA), methyl ester of N9-nitro-L-arginine (NAME), N9-nitro-1-arginine (NNA), N9amino-t may be mentioned more particularly. arginine (NAA), N9'N9-dimethyl-arginine (asymmetric dimethylarginine, referred to as ADMA), diphenyleneiodonium chloride, 2- (4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxy 3-oxide, 7-nitroindazole, N (5) - (1-iminoethyl) -L-ornithine, aminoguanidine, canavanine and ebselen.

Without questioning the effectiveness of these products, it is noted that these are chemical compounds that can induce inconvenience to the user or adverse side effects, which generally prefers to use natural products.

The object of the present invention is to provide a novel NO-synthase inhibitor which is a natural inhibitor of NO-synthase.

Surprisingly and unexpectedly, Applicant has demonstrated that CuDIPS has the property of being a NO-synthase inhibitor, particularly inducible NO-synthase (NOS 2) which makes it a good candidate for uses in applications where it is interesting to use a NO-synthase inhibitor, particularly in cosmetics.

Copper diisopropyl salicylate (CuDIPS) is a known compound whose synthesis is described in "Journal of Medicinal Chemistry", 1976, Vol. 19, n, p 135-148. This document as well as US Pat. No. 4,221,785 also describe the anti-inflammatory and anti-ulcer properties of this cupric complex which can be administered parenterally, in particular subcutaneously, and orally. International patent application WO 84/04922 describes this compound as an anti-tumor agent administered intramuscularly.

CuDIPS is furthermore described for its activity in the protection of the skin against ultraviolet radiation (EP 0293579).

However, it is not described as NO-synthase inhibitor.

The invention therefore firstly relates to the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to inhibit the NO-synthase .

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By physiologically acceptable medium, an environment compatible with the skin, the mucous membranes, the nails, the hair is understood.

The second object of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended for application in all fields. in which inhibition of NO-synthases is necessary, particularly in the cutaneous and / or capillary domain.

et/ou la mélanogenèse, et/ou la réponse aux variations environnementales (homéostasie). The CuDIPS or the composition containing it may be used to slow down or even inhibit cell differentiation and / or proliferation, and / or vasodilation,

and / or melanogenesis, and / or response to environmental variations (homeostasis).

Thus, the third object of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to slow or even inhibit the differentiation and / or cell proliferation, particularly to regulate, slow down or even inhibit the growth of the epidermis and / or to treat hyperproliferative disorders such as psoriasis.

The fourth subject of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to inhibit the degradation and / or destroying the cells and inhibiting the apoptotic processes, particularly skin cells, very particularly keratinocytes and / or treating the intrinsic and / or extrinsic aging of the cells, particularly the cells of the skin.

The fifth subject of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to inhibit or even eliminate the immunological processes and / or inflammation related to the synthesis of NO, such as contact hypersensitivity reactions and / or allergic manifestations and / or the immune response, particularly in the skin.

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Especially the CuDIPS or the composition are intended to reduce or inhibit cutaneous inflammation, particularly neurogenic skin inflammatory processes, and therefore to treat so-called sensitive skin.

The sixth subject of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to increase the barrier effect of skin or skin hydration.

The seventh object of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended for treating rosacea and / or cutaneous erythema, particularly erythema induced by ultraviolet radiation and / or localized or diffuse erythematous rashes of the skin such as those caused by drugs, toxins and / or viral or bacterial infections.

The eighth object of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to inhibit the melanogenesis induced by the ultraviolet radiation of type A and / or B and / or to treat disorders of the hypermelanosis type.

The ninth object of the invention is the use of an effective amount of CuDIPS, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to control perspiration and / or to inhibit hair loss.

According to the invention, the composition comprising CuDIPS can be a cosmetic or dermatological composition. Preferably according to the invention, the composition is a cosmetic composition.

Preferably according to the invention, the CuDIPS or the composition comprising it is applied to the skin in a topical manner.

According to the invention, the amount of CuDIPS extract used in the composition is, of course, a function of the desired effect and can therefore vary in a wide range.

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 measured.

10-4o/ en une quantité représentant de 10-4% à 20% du poids total de la composition et préférentiellement en une quantité représentant de 5. 10-3% à 10% du poids total de la composition. To give an order of magnitude, according to the invention, the CuDIPS can be used

10-4o / in an amount representing 10-4% to 20% of the total weight of the composition and preferably in an amount representing from 5. 10-3% to 10% of the total weight of the composition.

Of course, according to the invention CuDIPS may be combined with other NO synthase inhibitors such as plant extracts such as, for example, an extract of at least one plant of the species Olea europaea or a Ginkgo biloba extract or a Vitis vinifera extract or an extract of green tea or cocoa.

The tenth object of the invention is a cosmetic treatment method for treating disorders related to the synthesis of NO, characterized in that it is used by application to the skin, to the hair, and / or to the mucous membranes. , a cosmetic composition comprising at least CuDIPS in a physiologically acceptable medium.

The cosmetic treatment method of the invention aims to improve the appearance of the individual affected by the disorders due to NO synthesis.

The cosmetic treatment method of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the usual technique of use of these compositions. For example, it is possible to apply creams, gels, serums, lotions, cleansing milks or sunscreen compositions to the skin or to dry hair, applications of a hair lotion. on wet hair, shampoos, or toothpaste applications on the gums.

Whatever the form of the composition according to the invention in which CuDIPS is used, it can be ingested, injected or applied to the skin (on any cutaneous area of the body), hair, nails or mucous membranes (oral , jugal, gingival, genital, conjunctival). Depending on the mode of administration, the composition according to the invention may be in any of the galenical forms normally used.

For topical application to the skin, the composition may be in the form of, in particular, an aqueous or oily solution or a dispersion of the lotion type or

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 serum, 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 with a soft consistency of cream or gel type aqueous or anhydrous, or microcapsules or microparticles, or vesicular dispersions of ionic and / or nonionic type.

These compositions are prepared according to the usual methods.

They may also be used for hair in the form of aqueous, alcoholic or aqueous-alcoholic solutions, or in the form of creams, gels, emulsions, foams or in the form of aerosol compositions also comprising a propellant under pressure.

For injection, the composition may be in the form of an aqueous lotion, oily or in the form of serum. For the eyes, it can be in the form of drops and for ingestion, it can be in the form of capsules, granules of syrups or tablets.

The amounts of the various constituents of the compositions according to the invention are those conventionally used in the fields under consideration.

These compositions comprise creams for cleaning, protection, treatment or care for the face, for the hands, for the feet, for large anatomical folds or for the body, (for example, day creams, night creams, make-up removing creams, foundation creams, sunscreen creams), fluid foundations, make-up removing milks, body care or care milks, sunscreen lotions, lotions, gels or mousse for the care of the skin, such as cleaning lotions, sunscreen lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, depilatory creams, compositions against insect bites, anti-pain compositions, compositions for treating certain skin diseases such as eczema, rosacea, psoriasis, lichens, severe pruritus.

The compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.

The compositions may also be packaged in the form of an aerosol composition also comprising a propellant under pressure.

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The composition according to the invention may also be a composition for hair care, and in particular a shampoo, a setting lotion, a treatment lotion, a cream or a styling gel, a dye composition (especially oxidation dyes) in the form of coloring shampoos, restructuring lotions for the hair, a permanent composition (in particular a composition for the first time of a perm), a lotion or an anti-fall gel, a pest control shampoo, etc.

The composition may also be for oral use, for example a toothpaste. In this case, the composition may contain adjuvants and additives customary for oral compositions and in particular surfactants, thickeners, humectants, polishing agents such as silica, various active ingredients such as fluorides, in particular especially sodium fluoride, and optionally sweetening agents such as sodium saccharin.

When the composition 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 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. The emulsion may further contain lipid vesicles.

When the composition is a solution or an oily gel, the fatty phase may represent more than 90% of the total weight of the composition.

In known manner, the cosmetic composition may also contain adjuvants 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 phase

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 aqueous and / or lipid spherules.

As oils or waxes that can be used in the invention, mention may be made of mineral oils (vaseline oil), vegetable oils (liquid fraction of shea butter, sunflower oil), animal oils (perhydrosqualene), synthetic oils ( Purcellin oil), silicone oils or waxes (cyclomethicone) and fluorinated oils (perfluoropolyethers), bees, carnauba or paraffin waxes. To these oils can be added fatty alcohols and fatty acids (stearic acid).

As emulsifiers that can be used in the invention, mention may be made, for example, of glycerol stearate, polysorbate 60 and the mixture of PEG-6 / PEG-32 / glycol stearate sold under the name Tefose® 63 by the company Gattefosse.

As solvents that can be used in the invention, mention may be made of lower alcohols, in particular ethanol and isopropanol, and propylene glycol.

As hydrophilic gelling agents that can be used in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, ethylcellulose and polyethylene.

The composition may contain other hydrophilic active agents such as proteins or protein hydrolysas, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and the like. hydroxy acids.

As lipophilic active agents, it is possible to use retinol (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives.

According to the invention the composition may combine at least one CuDIPS extract with other active agents intended in particular for the prevention and / or treatment of cutaneous affections. Among these active agents, there may be mentioned by way of example: the agents modulating the differentiation and / or the proliferation and / or the

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 skin pigmentation such as retinoic acid and its isomers, retinol and its esters, vitamin d and its derivatives, kojic acid or hydroquinone; antibacterials such as clindamycin phosphate, erythromycin or antibiotics of the tetracycline class; antiparasitics, in particular metronidazole, crotamiton or pyrethrinoids; antifungals, in particular compounds belonging to the class of imidazoles such as econazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family, such as terbinafine, or octopirox; non-steroidal anti-inflammatory agents such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid; anesthetic agents such as lidocaine hydrochloride and its derivatives; antipruritic agents such as thenaldine, trimeprazine or cyproheptadine; keratolytic agents such as alpha-and beta-hydroxycarboxylic acids or beta-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, salicylic acid, citric acid and generally fruit acids, and n-octanoyl-5-salicylic acid; anti-free radical agents, such as alpha-tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and its esters; anti-seborrhoeic agents such as progesterone; anti-dandruff such as octopirox or zinc pyrithione; anti-acne drugs such as retinoic acid or benzoyl peroxide; plant or microbial extracts, peptides and their derivatives, for example the tripeptide Lys-Pro-Val (KPV).

The following examples and compositions illustrate the invention without limiting it in any way. In the compositions, the proportions indicated are percentages by weight.

Example 1: Biological Activity of CuDIPS: The activity of CuDIPS on inducible NO-synthase was evaluated in the test described by Heck et al. (J.B.C., 267, 30, 21277-21280, October 25, 1992).

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 This test aims to show the decrease in the concentration of nitrate and nitrite, in fine, after stimulation of NO-synthase 2.

C : contrôle de spécificité de l'inhibition : N9-monométhyl-L-arginine (forme D) à 200 um. The following controls were introduced into the tests: A: positive control (induction of the enzyme): mixtures of interferon-γ (1000u / ml) and interleukin 1-ss (100 μ / ml); B: negative control (maximum inhibition): N9-monomethyl-L-arginine (L-form) at 200! lm;

C: specificity control of the inhibition: N9-monomethyl-L-arginine (Form D) at 200 μm.

To determine the activity of the product to be tested, the amount of stable reaction products of NO (nitrites and nitrates) is measured using the "nitric colorimetric assay" kit sold by Boehringer under the reference 1756.28.

CuDIPS was tested at concentrations of 200 M, 100 M and 20 M in ethanol.

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Product <SEP> tested <SEP>% <SEP> inhibition
<tb> A <SEP> 0
<tb> B <SEP> 100
<tb> C <SEP> 0
<tb> CUDIPS <SEP>: <SEP> 200 <SEP> M67, <SEP> 8
<tb> CUDIPS <SEP>: <SEP> 100 <SEP> M53, <SEP> 9
<tb> CUDIPS <SEP>: <SEP> 20 <SEP> M28, <SEP> 8
<Tb>
CuDIPS has an inhibitory effect on inducible NO synthase.

Example 2: Examples of formulations illustrating the invention. These compositions were obtained by simple mixing of the various components.

<Tb>
<Tb>

Composition <SEP> 1 <SEP>: <SEP> gel <SEP> for <SEP> the <SEP> face
<tb> CuDIPS <SEP> 0.10 <SEP>%
<tb> Methylparaben <SEP> 0.20 <SEP>%
<tb> Carbomer <SEP> 0.70 <SEP>%
<tb> Polyethylene Glycol <SEP> (80E) <SEP> 10.00 <SEP>%
<tb> Imidazolidinyl <SEP> Urea <SEP> 0.30 <SEP>%
<Tb>

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<Tb>
<tb> Triethanolamine <SEP> 0.58 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 2 <SEP>: <SEP> lotion
<tb> CuDIPS <SEP> 2.00 <SEP>%
<tb> Antioxidant <SEP> 0.05 <SEP>%
<tb> Isopropanol <SEP> 40.00 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 3 <SEP>: <SEP> gel <SEP> for <SEP><SEP> care
<tb> CuDIPS <SEP> 2.00 <SEP>%
<tb> Hydroxypropylcellulose * <SEP> 1.00 <SEP>%
<tb> Antioxidant <SEP> 0.05 <SEP>%
<tb> Isopropanol <SEP> 40.00 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 4 <SEP>: <SEP> cream <SEP> of <SEP> care <SEP> (emulsion <SEP> oil <SEP> in <SEP> water)
<tb> CuDIPS <SEP> 5.00 <SEP>%
<tb> Stearate <SEP> of <SEP> glycerol <SEP> 2.00 <SEP>%
<tb> Polysorbate <SEP> 60 ** <SEP> 1.00 <SEP>%
<tb> Stearic acid <SEP><SEP> 1.40 <SEP>%
<tb> Triethanolamine <SEP> 0.70 <SEP>%
<tb> Carbomer <SEP> 0.40 <SEP>%
<tb> Fraction <SEP> liquid <SEP> of <SEP> butter <SEP> of <SEP> shea butter <SEP> 12,00 <SEP>%
<tb> Perhydrosqualene <SEP> 12.00 <SEP>%
<tb> Antioxidant <SEP> 0.05 <SEP>%
<tb> Perfume <SEP> 0,50 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 5 <SEP>: <SEP> shampoo
<tb> CuDIPS <SEP> 0.50 <SEP>%
<tb> Hydroxypropylcellulose * <SEP> 1.00 <SEP>%
<tb> Fragrance <SEP> 0, <SEP> 50 <SEP>%
<tb> Conservative <SEP> 0, <SEP> 30 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<Tb>

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<Tb>
<tb> Composition <SEP> 6 <SEP>: <SEP> cream <SEP> of <SEP> care <SEP> (emulsion <SEP> oil / water)
<tb> CuDIPS <SEP> 5.00 <SEP>%
<tb> Stearate <SEP> of <SEP> glycerol <SEP> 2.00 <SEP>%
<tb> Polysorbate <SEP> 60 ** <SEP> 1.00 <SEP>%
<tb> Stearic acid <SEP><SEP> 1.40 <SEP>%
<tb><SEP> n-octanoyl-5-salicylic acid <SEP> 0.50 <SEP>%
<tb> Triethanolamine <SEP> 0.70 <SEP>%
<tb> Carbomer <SEP> 0.40 <SEP>%
<tb> Fraction <SEP> liquid <SEP> of <SEP> butter <SEP> of <SEP> shea butter <SEP> 12,00 <SEP>%
<tb> Perhydrosqualene <SEP> 12.00 <SEP>%
<tb> Antioxidant <SEP> 0.05 <SEP>%
<tb> Perfume <SEP> 0,50 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 7 <SEP>: <SEP> gel <SEP> anti-pain
<tb> CuDIPS <SEP> 3, <SEP> 00 <SEP>%
<tb> -Hydroxypropylcellulose * <SEP> 1, <SEP> 00 <SEP>%
<tb> Antioxidant <SEP> 0.05 <SEP>%
<tb> Hydrochloride <SEP> of <SEP> lidocaine <SEP> 2.00 <SEP>%
<tb> Isopropanol <SEP> 40.00 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 8 <SEP>: <SEP> cream <SEP> of <SEP> care <SEP> of <SEP> erythema <SEP> solar <SEP> (oil-in-oil emulsion <SEP> water)
<tb> CuDIPS <SEP> 5.00 <SEP>%
<tb> Stearate <SEP> of <SEP> glycerol <SEP> 2.00 <SEP>%
<tb> Polysorbate <SEP> 60 ** <SEP> 1, <SEP> 00 <SEP>%
<tb> Stearic acid <SEP><SEP> 1.40 <SEP>%
<tb><SEP> Glycyrrhetinic acid <SEP> 2.00 <SEP>%
<tb> Triethanolamine <SEP> 0.70 <SEP>%
<tb> Carbomer <SEP> 0.40 <SEP>%
<tb> Fraction <SEP> liquid <SEP> of <SEP> butter <SEP> of <SEP> shea butter <SEP> 12,00 <SEP>%
<tb> Oil <SEP> of <SEP> sunflower <SEP> 10.00 <SEP>%
<tb> Antioxidant <SEP> 0.05 <SEP>%
<tb> Perfume <SEP> 0,50 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<Tb>

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<Tb>
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 9 <SEP>: <SEP> gel <SEP> for <SEP><SEP> treatment <SEP> of <SEP> acne
<tb> CuDIPS <SEP> 5.00 <SEP>%
<tb> Acid <SEP> all <SEP> trans <SEP> retinoic <SEP> 0.05 <SEP>%
<tb> Hydroxypropylcellulose * <SEP> 1.00 <SEP>%
<tb> Antioxidant <SEP> 0.05 <SEP>%
<tb> Isopropanol <SEP> 40.00 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<tb> Water <SEP> qsp <SEP> 100 <SEP>%
<tb> Composition <SEP> 10 <SEP>: <SEP> lotion <SEP> for <SEP> to eliminate <SEP><SEP> scars <SEP> due <SEP> to <SEP> acne
<tb> CuDIPS <SEP> 5.00 <SEP>%
<tb><SEP> Glycolic acid <SEP> 50,00 <SEP>%
<tb> Hydroxypropylcellulose * <SEP> 0.05 <SEP>%
<tb> Conservative <SEP> 0.30 <SEP>%
<tb> NaOH <SEP> qsp <SEP> pH <SEP> = <SEP> 2,8
<tb> Ethanol <SEP> qsp <SEP> 100 <SEP>%
<Tb>
*: Klucel H &commat; sold by Hercules **: Tween 60 &commat; sold by the company ICI

Claims (21)

 1. Use of an effective amount of copper diisopropyl salicylate (CuDIPS), in a physiologically acceptable medium, in a composition or for the preparation of a composition, the CuDIPS or the composition being intended to inhibit NO-synthase. 2. Use according to the preceding claim, characterized in that the copper diisopropyl salicylate or the composition are intended to slow or even inhibit cell differentiation and / or proliferation. 3. Use according to the preceding claim, characterized in that the copper diisopropyl salicylate or the composition are intended to slow or inhibit the growth of the epidermis and / or to treat hyperproliferative disorders. 4. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit the degradation and / or destruction of the cells. 5. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit cellular apoptotic processes. 6. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to treat intrinsic aging and / or extrinsic. 7. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit or suppress the immunological and / or inflammatory processes. 8. Use according to claim 7, characterized in that the copper diisopropyl salicylate or the composition are intended to treat contact hypersensitivity reactions and / or allergic manifestations and / or the immune response. 9. Use according to claim 7, characterized in that the copper diisopropyl salicylate or the composition are intended to reduce or inhibit <Desc / Clms Page number 16>  skin inflammation. 10. Use according to claim 9, characterized in that the copper diisopropyl salicylate or the composition are intended to treat cutaneous neurogenic inflammatory processes. 11. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to treat so-called sensitive skin. 12. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to increase the barrier effect of the skin or cutaneous hydration. 13. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to treat erythema, particularly erythema induced by ultraviolet radiation.  14. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to treat localized or diffuse erythematous rashes of the skin.  15. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to treat rosacea.  16. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit the melanogenesis induced by ultraviolet radiation type A and / or B and / or to treat hypermelanosis type disorders.  17. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to control sweating.  18. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit hair loss.  19. Use according to any one of the preceding claims, <Desc / Clms Page number 17>  characterized in that the copper diisopropyl salicylate is in an amount 10-4o / representative of 10-4% to 20% of the total weight of the composition.

20. Use according to the preceding claim, characterized in that the 10-3o / copper diisopropyl salicylate is in an amount representing 5. 10-3% to 10% of the total weight of the composition. 21. Cosmetic treatment process for treating disorders related to the synthesis of NO, characterized in that a cosmetic composition comprising at least one embodiment is applied to the skin, to the hair, and / or to the mucous membranes. less copper diisopropyl salicylate in a physiologically acceptable medium.