WO2002102342A1

WO2002102342A1 - No-synthase inhibitor and uses thereof

Info

Publication number: WO2002102342A1
Application number: PCT/FR2002/002061
Authority: WO
Inventors: Marie-Madeleine Cals-Grierson
Original assignee: L'oreal
Priority date: 2001-06-15
Filing date: 2002-06-14
Publication date: 2002-12-27
Also published as: FR2825923A1; FR2825923B1

Abstract

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

Description

NO synthase inhibitor and uses

The subject of the present invention is 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 NO synthase.

The term NO-synthase covers a family of enzymes which ensure the enzymatic transformation of l-arginine into citrulline, a reaction during which a gaseous mediator with multiple functions is produced, nitrogen monoxide or no.

NO-synthases exist in three forms, two constitutive forms, nomenclature grouping together neuronal NO-synthase (or NOS 1) and 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 the contrary indication 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 reduction 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 NO-synthase or its induction or which inhibit the activity of the no-product.

Nitric oxide has, by its structure, an additional electron making it extremely chemically reactive. It is well known that such compounds are harmful and we seek to limit their production as much as possible. Thus, in the case of nitric oxide, the 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 cells linked to its hyperreactivity due to its structure comprising an additional electron, it is recognized among other things as intervening particularly in the cardiovascular system (regulator of blood pressure with vasodilator effect, inhibitor of platelet aggregation with effect anticoagulant), in the nervous system (memory, modulation of neurotransmitter release), in the immunological system (modulation of immune defenses, inflammation, involvement in autoimmune pathologies).

It is now well recognized that NO plays a predominant role in the skin. NO can be synthesized by all varieties of cells constituting the skin and as such it is involved in multiple and complex regulatory processes such as the regulation of cell differentiation and / or proliferation, vasodilation, melanogenesis, response to environmental variations (homeostasis). Its involvement in cell differentiation and proliferation (stimulating effect), particularly in keratinocytes, associates it with the growth of the epidermis and scarring as well as hyperproliferative disorders (psoriasis). Due to its electronic hyperreactivity which can lead to degradation or even destruction of cells, NO is involved in the apoptotic processes and in the intrinsic and / or extrinsic aging of the skin.

It is involved in the skin's immunological and inflammatory processes. It is indeed commonly accepted that NO plays a role in contact hypersensitivity reactions, in allergic skin manifestations, in the skin's immune response. Similarly, in addition to its direct proinflammatory role, it is the mediator between neuropeptides such as substance P el or the peptide associated with the calcitonin gene (Calcitonin Gene Related Peptide or CGRP) in the skin reaction processes of neurogenic origin, d 'where its involvement in so-called sensitive skin phenomena. Application WO97 / 15280 has thus demonstrated the advantage of using a NO-synthase inhibitor in the treatment of sensitive skin.

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

The involvement of NO in vasodilation makes it associated with skin erythemas, particularly erythemas induced by ultraviolet radiation, localized or diffuse erythematous eruptions of the skin such as those caused by drugs, toxins and / or viral or bacterial infections, rosacea.

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

Finally, NO seems to be involved in the control of sweating as well as in hair loss. We therefore understand the interest that exists in having inhibitors of NO-synthases. In this regard, numerous inhibitors have already been proposed in the prior art. Mention may more particularly be made of N ⁹ -monomethyl-L-arginine (NMMA), the methyl ester of N ^g -nitro-L-arginine (NAME), N ⁹ -nitro-l-arginine (NNA), N ⁹ -amino-1- arginine (NAA), N ^g, N ⁹ -dimethyl-arginine (asymmetric dimethylarginine, called ADMA), diphenyleneiodonium chloride, 2- (4-carboxyphenyl) -4,4,5 , 5-tetramethylimidazoline-1-oxy-3-oxide, the

7-nitroindazole, N (5) - (1 -iminoethyl) -L-omithine, aminoguanidine, canavanine and ebselen.

Without questioning the effectiveness of these products, we note that these are chemical compounds which can induce inconvenience in the user or even harmful side effects, who generally prefer to use natural products. The object of the present invention is to provide a new inhibitor of NO-synthase which is moreover a natural inhibitor of NO-synthase.

Surprisingly and unexpectedly, the applicant has demonstrated that CuDIPS has the property of being an inhibitor of NO synthase, particularly of 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 ° 1, 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 also described for its activity in protecting the skin against ultraviolet radiation (EP 0293579).

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

A primary object of the invention is therefore 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 NO synthase.

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

A 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 an inhibition of NO synthases proves necessary, particularly in the cutaneous and / or capillary field.

The CuDIPS or the composition containing it can be used to slow down or even inhibit cell differentiation and / or proliferation, and / or vasodilation, and or melanogenesis, and or the response to environmental variations (homeostasis).

Thus, invβvition has as its third object 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 down or even inhibit 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 for example psoriasis.

A fourth 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 degradation and / or the destruction of cells and to inhibit apoptotic processes, particularly of skin cells, very particularly of keratinocytes and or to treat the intrinsic and or extrinsic aging of cells, particularly of skin cells.

A fifth 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 or even suppress the related symptoms. to immunological and or inflammatory phenomena linked to the synthesis of NO, such as for example contact hypersensitivity reactions and / or allergic manifestations and / or the immune response, particularly in the skin. According to another aspect, the CuDIPS or the composition are intended to reduce or even inhibit skin irritation, caused by external agents. The skin irritant effect is a response of the skin most often resulting in redness, pain or tingling, this response being caused by chemicals of natural or synthetic origin applied topically to the skin. This irritation is accompanied by an alteration in the function and or in the epithelial structure, directly linked to the effect of the irritant product. The CuDIPS or the composition containing it are suitable in the case of skin reactions linked to processes of neurogenic origin such as certain skin rednesses, and therefore to be treated to reduce or suppress the manifestations of so-called sensitive skin. These are aspecific reactions, distinguished from the mechanisms of allergy or inflammation. These symptoms are in particular subjective signs, which are essentially dysaesthetic sensations. By dysesthetic sensations is meant more or less painful sensations felt in a skin area such as tingling, tingling, itching or itching, heating, discomfort, tightness, etc. Sensitive skin can be divided into two main clinical forms, irritable and / or reactive skin, and intolerant skin. Irritable and / or reactive skin is skin which reacts by pruritus, that is to say by itching or tingling, to various factors such as the environment, emotions, food, wind, friction, razor, soap, surfactants, hard water with a high concentration of limestone, temperature variations or wool. In general, these signs are associated with dry skin with or without sores or with skin that presents with erythema, which is non-inflammatory. Intolerant skin is skin that reacts with sensations of heating, tightness, tingling and / or redness, to various factors such as the environment, emotions, food and certain cosmetic products. In general, these signs are associated with hyperseborrheic or acne-prone skin with or without sores and erythema.

"Sensitive" scalps have a more unequivocal clinical semiology: the sensations of pruritus and / or tingling and / or overheating are essentially triggered by local factors such as friction, soap, surfactants, hard water with a high concentration of limestone, shampoos or lotions. These sensations are also sometimes triggered by factors such as the environment, emotions and / or food. Erythema and hyperseborrhea of the scalp and dandruff are frequently associated with the above signs. A sixth 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 increase the barrier effect of skin or skin hydration.

A seventh 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 for treating rosacea and / or skin 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 melanogenesis induced by type A and or B ultraviolet radiation and / or to treat hypermelanosis type disorders.

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 sweating and / or to inhibit or decrease 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 topically.

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 to a large extent.

To give an order of magnitude, according to the invention, the CuDIPS can be used in an amount representing from 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 can 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 an extract of Ginkgo biloba or a extract of Vitis vinifera or an extract of green tea or cocoa.

The tenth subject of the invention is a cosmetic treatment process with a view to treating disorders linked to the synthesis of NO, characterized in that it is used by application on the skin, on the hair, and / or on 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 the synthesis of NO.

The cosmetic treatment process of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the technique of usual use of these compositions. Thus for example it is possible to carry out applications of creams, gels, serums, lotions, cleansing milks or anti-sun compositions on the skin or on dry hair, applications of a hair lotion on wet hair, shampoos, or even toothpaste applications on the gums.

Whatever the form of the composition according to the invention in which the CuDIPS is used, it can be ingested, injected or applied to the skin (on any cutaneous zone of the body), the hair, the nails or the mucous membranes (buccal , jugale, gingival, genital, conjunctiva). Depending on the mode of administration, the composition according to the invention can be in all the dosage forms normally used.

For topical application to the skin, the composition may take the form in particular of an aqueous or oily solution or of a dispersion of the lotion or serum type, of emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersion of a phase fatty in an aqueous phase (O / W) or vice versa (W / O), or of suspensions or emulsions of soft consistency of the aqueous or anhydrous cream or gel type, or of microcapsules or microparticles, or of vesicular dispersions of the ionic type and / or nonionic. These compositions are prepared according to the usual methods. They can also be used for the hair in the form of aqueous, alcoholic or hydroalcoholic solutions, or in the form of creams, gels, emulsions, foams or also in the form of aerosol compositions also comprising a propellant under pressure.

For injection, the composition may be in the form of an aqueous, oily lotion or in the form of a 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 considered.

These compositions constitute in particular cleansing, protective, treatment or care creams 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 remover creams, foundation creams, sunscreen creams), fluid foundations, make-up removal milks, body protection or care milks, anti-sun milks, lotions, gels or foams for care of the skin, such as cleansing lotions, sunscreen lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, aftershave gels or lotions, depilatory creams, compositions against insect bites, pain relieving 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 can also be packaged in the form of an aerosol composition also comprising a propellant under pressure.

The composition according to the invention can also be a composition for hair care, and in particular a shampoo, a styling lotion, a treating lotion, a styling cream or gel, a composition of dyes (in particular oxidation dyes) in the form of coloring shampoos, restructuring hair lotions, a perm composition (in particular a composition for the first time of a perm), a lotion or a fall prevention gel, an antiparasitic shampoo, etc.

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

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, waxes, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the cosmetic 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, in addition, contain lipid vesicles.

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

In a 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 coloring matters. The amounts of these various adjuvants are those conventionally used in the cosmetic 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.

As oils or waxes which can be used in the invention, mention may be made of mineral oils (petroleum jelly 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), beeswax, carnauba or paraffin. Fatty alcohols and fatty acids (stearic acid) can be added to these oils. As emulsifiers which can be used in the invention, there may be mentioned, for example, glycerol stearate, polysorbate 60 and the mixture of PEG-6 / PEG-32 / glycol stearate sold under the name Tefose ^R 63 by the company Gattefosse.

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

As hydrophilic gelling agents which can be used in the invention, mention may be made of carboxyvinyl polymers (carbomers), 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, polyethylene.

The composition can contain other hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, pallantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.

As lipophilic active agents, retinol (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives can be used.

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

- 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 even 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 or beta-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycol acid, lactic acid, salicylic acid, acid citric 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 chelating agents or ascorbic acid and its esters;

- anti-seborrheic drugs such as progesterone;

- anti-dandruff agents such as octopirox or zinc pyrithione;

- anti-acne drugs such as retinoic acid or benzoyl peroxide; - plant or microbial extracts,

- peptides and their derivatives such as 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., vol. 267, n ° 30, 21277-21280, October 25, 1992). The objective of this test is to show the decrease in the concentration of nitrate and nitrite, in fine, after stimulation of NO-synthase 2.

The following controls were introduced in the tests:

A: positive control (induction of the enzyme): mixtures of interferon-γ (1000u / ml) and interleukin 1 -β (100 u / ml);

B: negative control (maximum inhibition): N ⁹ -monomethyl-L-arginine (form L) at 200 μm; C: specificity control of inhibition: N ⁹ -monomethyl-L-arginine (form D) at

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

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

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.

Composition 1: face gel

CuDIPS 0.10%

Methylparaben 0.20%

Carbomer 0.70%

Polyethylene glycol (80E) 10.00%

Imidazolidinyl urea 0.30%

Triethanolamine 0.58%

Water qs 100%

Composition 2: lotion

CuDIPS 2.00%

Antioxidant 0.05%

Isopropanol 40.00%

Preservative 0.30%

Water qs 100% Composition 3: CuDIPS care gel 2.00%

Hydroxypropylcellulose * 1.00% Antioxidant 0.05% Isopropanol 40.00% Preservative 0.30% Water qs 100%

Composition 4: care cream (oil in water emulsion) CuDIPS 5.00%

Glycerol stearate 2.00%

Polysorbate 60 ** 1, 00%

Stearic acid 1.40%

Triethanolamine 0.70% Carbomer 0.40%

Liquid fraction of shea butter 12.00%

Perhydrosqualene 12.00%

Antioxidant 0.05%

Perfume 0.50% Preservative 0.30%

Water qs 100%

Composition 5: CuDIPS shampoo 0.50% Hydroxypropylcellulose * 1.00% Perfume 0.50% Preservative 0.30% Water qs 100%

Composition 6: care cream (oil / water emulsion)

CuDIPS 5.00%

Glycerol stearate 2.00%

Polysorbate 60 ^** 1, 00%

Stearic acid 1.40% n-Octanoyl-5-salicylic acid 0.50%

Triethanolamine 0.70% ^•

Carbomer 0.40%

Liquid fraction of shea butter 12.00% Perhydrosqualene 12.00% Antioxidant 0.05% Perfume 0.50% Preservative 0.30% Water qs 100%

Composition 7: CuDIPS pain relief gel 3.00%

Hydroxypropylcellulose ^* 1.00% Antioxidant 0.05%

Lidocaine hydrochloride 2.00%

Isopropanol 40.00%

Preservative 0.30%

Water qs 100%

Composition 8: care cream for solar erythema (emulsio> nn hhuuiillee - ddaannss - eeaauu))

CuDIPS 5.00%

Glycerol stearate 2.00%

Polysorbate 60 ** 1.00% Stearic acid 1.40%

Glycyrrhetinic acid 2.00%

Triethanolamine 0.70%

Carbomer 0.40%

Liquid fraction of shea butter 12.00% Sunflower oil 10.00%

Antioxidant 0.05%

Perfume 0.50%

Preservative 0.30%

Water qs 100%

Composition 9: gel for the treatment of acne CuDIPS 5.00%

All trans retinoic acid 0.05% Hydroxypropylcellulose ^* 1.00% Antioxidant 0.05% Isopropanol 40.00% Preservative 0.30% Water qs 100% Composition 10: lotion to remove scars due to acne

CuDIPS 5.00%

Glycolic acid 50.00%

Hydroxypropylcellulose * 0.05%

Preservative 0.30%

NaOH qs pH = 2.8

Ethanol qs 100%

*: Klucel H® sold by the company Hercules **: Tween 60® sold by the company HERE

Claims

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 down 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 down or even 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 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 and / or extrinsic aging.

7. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit or even 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 for treating contact hypersensitivity reactions and or allergic manifestations and / or the immune response.

9. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to treat the processes neurogenic skin inflammatory.

10. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended for treating so-called sensitive skin

11. 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 the skin hydration.

12. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to treat erythemas, particularly erythemas induced by ultraviolet radiation.

13. 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.

14. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended for treating rosacea.

15. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit melanogenesis induced by ultraviolet radiation type A el or B and / or to treat disorders of hypermelanosis type.

16. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to control sweating.

17. Use according to claim 1, characterized in that the copper diisopropyl salicylate or the composition are intended to inhibit hair loss.

18. Use according to any one of the preceding claims, characterized in that the copper diisopropyl salicylate is in an amount representing from 10 ^'4 % to 20% of the total weight of the composition.

19. Use according to the preceding claim, characterized in that the copper diisopropyl salicylate is in an amount representing from 5.10 ^"3 % to 10% of the total weight of the composition.

20. Cosmetic treatment process with a view to treating disorders linked to the synthesis of NO, characterized in that use is made, by application to the skin, to the hair, and / or to the mucous membranes, of a cosmetic composition comprising less copper diisopropyl salicylate in a physiologically acceptable medium.