EP1278509A1 - Lipochroman-6 as no-synthase inhibitor and uses - Google Patents

Abstract

The invention concerns the use of an efficient amount of lipochroman-6 in a physiologically acceptable medium, in a composition or for preparing a composition, the lipochroman-6 or the composition being designed to inhibit NO-synthase.

Description

 Lipochroman-6 as a NO-synthase inhibitor and uses

The subject of the present invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit NO synthase.

The term NO-synthase covers a family of enzymes which ensure the enzymatic catalysis of L-arginine into citrulline, during which catalysis is produced a gaseous mediator with multiple functions, 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 of the isoforms of the enzyme.

Thus, according to the invention, the term NO-synthase inhibitors is understood to mean any product which, in the end, results, notwithstanding the isoform of NO-synthase, in 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 NO produced.

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 particularly involved 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 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 intervenes in multiple and complex regulatory processes such as the regulation of cell differentiation and / or proliferation, vasodilation, melanogenesis , the response to environmental variations (homeostasis. Its involvement in cell differentiation and proliferation (stimulating effect), particularly of keratinocytes, associates it as well with the growth of the epidermis and scarring as with hyperproliferative disorders ( Due to its electronic hyperreactivity which can lead to cell degradation or even destruction, NO is involved in apoptotic processes and in the intrinsic and / or extrinsic aging of the skin. It intervenes in the cutaneous 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 and / or the peptide associated with the calcitonin gene (calcitonin gene related peptide or CGRP) in cutaneous neurogenic inflammatory processes, hence its implication in so-called sensitive skin phenomena. The involvement of NO in vasodilation makes it associated with skin erythema, 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, rosacea. NO is recognized as an intermediate in melanogenesis induced by type B ultraviolet radiation (UVB). It is also one of the factors involved in hypermelanosis-like disorders. NO also seems to be involved in the control of sweating as well as in that of lipolysis (inhibitory effect) or even in hair loss. Finally, NO is known to have an influence on the barrier function of the skin and therefore on its hydration (inhibitory effect).

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 ^G -monomethyl-L-arginine (NMMA), the methyl ester of N ^G -nitro-L-arginine (NAME), N ^G -nitro-L-arginine (NNA), N ^G - amino-L-arginine (NAA), N ^G .N ^G -dimethyl-arginine (asymmetric dimethylarginine, called ADMA), diphenyleneiodonium chloride, 2- (4-carboxyρhenyl) -4,4,5 , 5-tetramethylimidazoline-1-oxy-3-oxide, the

7-nitroindazole, N (5) - (1-iminoethyl) -L-ornithine, Paminoguanidine, 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 lipochroman-6 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 proves interesting to use an inhibitor of NO-synthase, particularly in cosmetics.

Lipochroman-6 is a compound corresponding to the general formula:

This compound is described in the prior art as an antioxidant, as a free radical scavenger, as an inhibitor of lipid peroxidation and as a cell protector against damage induced by peroxynitrite. However, it is not described as an inhibitor of NO-synthase.

The primary object of the invention is therefore the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-β or the composition being intended to inhibit NO synthase.

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

A second object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, the lipochroman-6 or the composition being intended for an application. in all areas in which inhibition of NO synthases is necessary, particularly in the skin and / or capillary area.

Lipochroman-6 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, the third object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended for slow down or even inhibit cell differentiation and / or proliferation, particularly to regulate the growth of the epidermis and / or treat hyperproliferative disorders such as psoriasis.

A fourth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit the degradation and / or 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 lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit or even suppress the immunological and or inflammatory processes 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. Particularly the lipochroman-6 or the composition are intended to decrease or even inhibit skin inflammation, particularly the neurogenic inflammatory skin processes, and therefore to treat so-called sensitive skin.

The sixth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to treat the rosacea and / or skin erythema, particularly erythema induced by ultraviolet radiation and / or localized or diffuse erythematous rashes on the skin such as those caused by drugs, toxins and / or viral or bacterial infections.

A seventh subject of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit the melanogenesis induced by ultraviolet radiation of type A and or B and / or to treat disorders of hypermelanosis type.

The eighth object of the invention is the use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to control the sweating and / or stimulating lipolysis and / or inhibiting hair loss and / or strengthening the barrier function of the skin and or stimulating hydration of the skin.

According to the invention, the composition comprising lipochroman-6 can be a cosmetic or dermatological composition. Preferably according to the invention, the composition is a cosmetic composition.

Preferably according to the invention, the lipochroman-6 or the composition comprising it is applied to the skin topically.

According to the invention, the amount of lipochroman-6 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, lipochroman-6 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 lipochroman-6 can be combined with other NO synthase inhibitors such as plant extracts, for example an extract of at least one plant of the species Olea europaea or an extract of Ginkgo biloba or an extract of Vitis vinifera or an extract of green tea or cocoa.

The ninth 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 lipochroman-6 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 usual technique for using 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 lipochroman-6 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 fatty phase 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 Ionic and / or nonionic type vesicular dispersions. 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 may 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 fall prevention lotion or 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 phase. fatty 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 ^ 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 (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, polyethylene.

The composition may contain other hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, aliantoin, 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 lipochroman-6 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 Peconazole, 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 or beta-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, salicylic acid, acid citric and generally fruit acids, and n-octanoyl-5-salicylic acid;

- anti-free radical agents, such as Palpha-tocopherol or its esters, superoxide dismutases, certain metal chelators 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.

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 lipochroman-6: The activity of lipochroman-6 on inducible NO synthase was evaluated in the test described by Heck et al. (JBC, Vol. 267, No. 30, 21277-21280, October 25, 1992). The objective of this test is to show the decrease in the nitrate concentration 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 (1000U7ml) and Interleukin 1-β (100 U / ml);

B negative control (maximum inhibition): N ^G- monomethyl-L-arginine (form L) at 200 μM; inhibition specificity control: N ^G -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.

Lipochroman-6 was tested at concentrations of 0.005% and 0.01% (weight / volume) in ethanol.

Lipochroman-6 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

0.1% Lipochroman-6

0.2% Methyiparaben

Carbomer 0.7%

Polyethylene glycol (80E) 10.0% Imidazolidinyl urea 0.3%

Triethanolamine 0.58%

Water qs 100% Composition 2: Lipochroman-6 Lotion 2.00% Antioxidant 0.05% Isopropanol 40.00% Preservative 0.30% Water qs100%

Composition 3: Lipochroman-6 gel for care 3.00%

Hydroxypropylcellulose ^* 1.00%

Antioxidant 0.05%

Isopropanol 40.00%

Preservative 0.30% Water qs100%

Composition 4: Care cream (oil in water emulsion)

Lipochroman-6 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: Lipochroman-6 shampoo 0.50% Hydroxypropylcellulose * 1.00% Perfume 0.50% Preservative 0.30% Water qs 100%

Composition 6: Care cream (oil / water emulsion) Lipochroman-6 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: Pain relief gel

Lipochroman-6 5.00%

Hydroxypropylcellulose * 1, 00%

Antioxidant 0.05%

Lidocaine hydrochloride 2.00% Isopropanol 40.00%

Preservative 0.30%

Water qs 100%

Composition 8: Sun erythema care cream (emulsioonn hhuuiillee - ddaannss- -eeaaui) Lipochroman-6 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

Lipochroman-6 5.00%

0.05% all trans retinoic acid

Hydroxypropylcellulose * 1.00% Antioxidant 0.05%

Isopropanol 40.00%

Preservative 0.30%

Water qs 100%

Composition 10: Lotion for eliminating scars due to acne

Lipochroman-6 3.00%

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

Example 3: Effect of composition 1 of Example 2 on sensitive skin. It has been shown that sensitive skin is characterized by a very strong neurosensory reactivity of the skin to topical application to the face of capsaicin. (Magnusson and Koskinen, Acta Derm. Venereol. (Stockh), 1996, 76, 129-132).

One of the most predictive signs of sensitive skin is itching

The composition of Example 2 was therefore tested on a population (15 volunteers) of people with the characteristics of sensitive skin, in comparison with the same composition not containing Lipochroman-6.

Composition and control are applied to the face at the angle of the cheeks, randomly double blind. 30 minutes after treatment, a 0.075% capsaicin cream is applied to the treated areas.

The itching sensation is then evaluated according to: 0 = none 1 = light

2 = moderate

3 = strong

The average results are presented in the following table:

The gel containing lipochroman-6 has a protective effect against the itching sensation induced by capsaicin

Claims

1. Use of an effective amount of lipochroman-6, in a physiologically acceptable medium, in a composition or for the preparation of a composition, lipochroman-6 or the composition being intended to inhibit NO-synthase. 2. Use according to the preceding claim, characterized in that the lipochroman-6 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 lipochroman-6 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 lipochroman- 6 or the composition are intended to inhibit the degradation and / or destruction of cells. 5. Use according to claim 1, characterized in that the lipochroman- 6 or the composition are intended to inhibit cellular apoptotic processes. 6. Use according to claim 1, characterized in that the lipochroman- 6 or the composition are intended to treat intrinsic and / or extrinsic aging. 7. Use according to claim 1, characterized in that the lipochroman- 6 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 lipochroman- 6 or the composition are intended for treating hypersensitivity reactions of contact and / or allergic manifestations and / or the immune response. 9. Use according to claim 7, characterized in that the lipochroman- 6 or the composition are intended to decrease or even inhibit skin inflammation. 10. Use according to claim 9, characterized in that the lipochroman-6 or the composition are intended for treating the neurogenic inflammatory skin processes. 11. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating so-called sensitive skin 12. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating erythemas, particularly erythemas induced by ultraviolet radiation. 13. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating localized or diffuse erythematous eruptions of the skin. 14. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended for treating rosacea. 15. Use according to claim 1, characterized in that the Iipochroman-6 or the composition are intended to inhibit melanogenesis induced by ultraviolet radiation type A and / or B and / or to treat disorders of the hypermelanosis type. 16. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to control sweating. 17. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to stimulate lipolysis. 18. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to inhibit hair loss. 19. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to reinforce the barrier function of the skin. 20. Use according to claim 1, characterized in that the lipochroman-6 or the composition are intended to stimulate the hydration of the skin. 21. Use according to any one of the preceding claims, characterized in that the lipochroman-6 is in an amount representing from 10 ^"4 % to 20% of the total weight of the composition. 22. Use according to the preceding claim, characterized in that the lipochroman-6 is in an amount representing from 5.10 ^"3 % to 10% of the total weight of the composition. 23. Cosmetic treatment method 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 at least less lipochroman-6 in a physiologically acceptable medium.