WO2010040603A1

WO2010040603A1 - Dithiolane compounds; compositions containing them; uses for photoprotecting the skin

Info

Publication number: WO2010040603A1
Application number: PCT/EP2009/061277
Authority: WO
Inventors: Xavier Marat
Original assignee: L'oreal
Priority date: 2008-10-10
Filing date: 2009-09-01
Publication date: 2010-04-15
Also published as: EP2337780A1; FR2937035A1; FR2937035B1; CN102177150A

Abstract

The present invention relates to novel dithiolane compounds of formula (I) below: formula (I), in which Y denotes 0, NR₁ or S; R₁ denotes a hydrogen atom; a saturated linear C₁-C₂₀ or branched C₃-C₂₀ or unsaturated C₂-C₂₀ alkyl hydrocarbon- based group; an aryl group optionally substituted with one or more hydroxyls and/or with one or more C₁-C₈ alkoxy radicals; R denotes a hydrogen atom; a saturated linear C₁-C₂₀or branched C₃-C₂₀ or unsaturated C₂-C₂₀ alkyl hydrocarbon- based group; a radical having the following formula (Ia), in which n = 0, 1, 2, 3 or 4; x = 0, 1, 2 or 3 and R₃, which may be identical or different, denote a hydrogen atom or a linear or branched C₁-C₄ alkyl such as methyl, ethyl or isopropyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NHR₁ and R₁ is other than hydrogen, R and Ri may form a ring. The invention also relates to the uses of these compounds for reinforcing the natural antioxidant protection of the skin against oxidative stress caused especially by UV radiation.

Description

Dithiolane compounds ; Compositions containing them; Uses for photoprotecting the skin

The present invention relates to novel dithiolane compounds of particular formula (I), to the cosmetic or pharmaceutical compositions containing them and finally to uses thereof for treating or preventing disorders induced by oxidative stress, especially caused by solar radiation .

The skin is the outermost organ of our body and is thus the first target for environmental stress factors, most particularly represented by the ultraviolet radiation of sunlight, UVB and UVA. Specifically, acute or chronic exposure to sunlight is known to induce deleterious biological and clinical effects on the body.

Skin damage caused by chronic exposure (repeated irradiation) or acute exposure (strong irradiation) to UV-A or UV-B has been extensively studied; it is especially known that:

- UV-B rays (290-300 nm; 5% of the total UV), which have the most energetic wavelengths, most especially affect the epidermal cells

(keratinocytes) , by acting on DNA;

- UV-A rays (320-400 nm; 95% of the total UV), which penetrate more deeply, reach the dermal cells such as the fibroblasts and act indirectly via the generation of free radicals; furthermore, prolonged exposure to ultraviolet radiation has the effect of stimulating the expression of collagenases, particularly type 1 matrix metalloprotease (MMP-I) .

At the cellular and molecular levels, the impact of UVB and UVA radiation induces various reactions, including direct and indirect induction of DNA lesions. Among the direct induction of DNA lesions, some are specific to UV radiation, for instance pyrimidine dimers and 6,4 photo-produced. In the event of an error during repair by the specialized enzymatic systems (nucleotide excision repair NER, or global excision repair GER) , they may be responsible for mutations that are themselves the cause of tumoural processes resulting in the development of skin cancers. Moreover, in cells derived from these tumours, a very high incidence of mutations characteristic of solar UV impact is found. These DNA lesions are also the cause of apoptosis processes inducing the formation of characteristic cells in the epidermis, the "sunburn cells". It will also be noted that UV is responsible at the cellular level for the generation of reactive oxygen species, which are themselves the cause of many biological effects, such as the induction of oxidative DNA damage (8-oxoguanine) or the induction of numerous genes .

Finally, in addition to the effects mainly described on the two major cell types of the skin, namely the keratinocytes that form the stratified and differentiated epidermis, and the fibroblasts that are responsible for the synthesis and renewal of the dermal extracellular matrix, UV rays also have an impact on the Langerhans cells, which have an antigen-presenting immunity function.

The deleterious effects of UV rays on the skin (erythema, photocarcinogenesis, photoageing, photo- immunosuppression, etc.) are induced by the direct action of UV rays on certain cellular chromophores such as DNA, but also by indirect action. Specifically, the energy transported by UV rays is capable of triggering the formation of activated oxygen species (AOS) , for instance singlet oxygen and the superoxide anion, by means of a photosensitization reaction involving endogenous photosensitizers such as riboflavins, bilirubins, phaeomelanin and porphyrin derivatives. The singlet oxygen and the superoxide anion undergo a cascade of reactions resulting in the production of other AOSs such as hydrogen peroxide and hydroxyl radicals. The AOSs thus generated damage DNA, cell membranes and certain proteins (enzymes, transcription factors, etc . ) .

Cells are equipped with an enzymatic antioxidant defence (Cu-Zn and Mn superoxide dismutases, catalases, glutathione peroxidases, etc.) and non-enzymatic antioxidant defence (vitamins E and C, thiols including glutathione, β-carotene, trace elements, etc.), whose role is to maintain the intracellular redox potential, but this defence capacity may be overloaded during an episode of intense oxidative stress.

The tripeptide glutathione (γ-L-glutamyl-L- cysteinylglycine or GSH) is the most widely occurring and abundant of the low molecular weight non-protein thiols. The majority of the intracellular GSH is found in reduced form (GSH) . Glutathione disulfide (GSSG) represents less than 0.5% of the total GSH. In most animal cells, the concentration of GSH is between 1 and 10 mM, whereas it is between about 0.5 and 10 μM in the plasma. The thiol function located on the cysteine residue gives it a redox potential (about -230 mV) that is predominant in redox metabolic phenomena. Its reductive and nucleophilic properties play a major role in protection against the oxidative impairment of fats, proteins and nucleic acids. Under a situation of oxidative stress, its protective and detoxifying role results mainly from its function as a coenzyme of glutathione peroxidases and glutathione-S-transferases . It also undergoes synergistic interactions with other components of the antioxidant protection system such as vitamin C, vitamin E, and superoxide dismutases.

Reducing the level of glutathione will thus affect the redox cellular balance. It is especially known that exposure to UV rays results in depletion of the level of intracellular GSH, thus increasing the sensitivity of the cells towards the oxidative stress.

Skin can be protected against the harmful effects of UV radiation by using sunscreens. These products contain molecules that absorb the harmful wavelengths before they reach the skin and damage it, thus preventing the acute and chronic effects of exposure to UV rays .

However, sunscreens do not have a global action. Although no screening agent exists that allows total absorption of the harmful wavelengths (UVB, UVA and long UVA) , a photoprotection strategy based on induction of the endogenous antioxidant defence systems offers advantageous perspectives.

There is thus a real need to find additional solutions in this field in order to reconstitute and/or preserve the level of endogenous glutathione after exposure to UV rays. This may be envisaged by stimulation with an active agent of the natural endogenous systems of cellular defence and/or repair after an episode of UV-induced stress.

Lipoic or thioctic acid (1, 2-dithiacyclopentane-3- valeric acid) is an endogenous dithiol widely found in plants and animals. It is a coenzyme of fat and carbohydrate metabolism in mitochondrial multienzyme complexes such as pyruvate dehydrogenase and α- ketoglutarate dehydrogenase. Lipoic acid also increases the cellular level of glutathione by regenerating oxidized glutathione (GSSG) and increasing the activity of γ-glutamylcysteine ligase (an enzyme that controls the synthesis of GSH) .

WO 2008/058 999 discloses siloxane or silane dithiolane compounds for increasing the level of glutathione after UV-induced depletion, especially the compound 5- (1, 2-dithiolan-3-yl) -N- [3- (trimethylsilyl) - propyl ] pentanamide and the compound (trimethyl- silyl) methyl 5- (1, 2-dithiolan-3-yl) pentanoate . However, the protection afforded by these active agents against the UVA daylight-induced depletion of GSH is still not fully satisfactory.

The Applicant has now discovered that certain dithiolane compounds of particular formula (I) that will be defined in detail hereinbelow make it possible to significantly increase the level of glutathione after UV-induced depletion when compared with the dithiolane compounds of the prior art, and thus make it possible to reinforce and/or preserve the natural antioxidant protection of the skin against oxidative stress caused especially by UV radiation.

One subject of the present invention is thus novel dithiolane compounds of particular formula (I) which will be defined in greater detail below.

A subject of the present invention is also a cosmetic or pharmaceutical composition comprising, in a physiologically acceptable medium, at least one dithiolane compound of formula (I) .

A subject of the present invention is also the cosmetic use of at least one dithiolane compound of formula (I) in a composition comprising a physiologically acceptable medium, for the purpose of reinforcing and/or preserving the natural antioxidant protection of skin, especially the endogenous system of antioxidant defence against oxidative stress caused especially by UV radiation.

A subject of the present invention is, in particular, the cosmetic use of at least one dithiolane compound of formula (I) in a composition comprising a physiologically acceptable medium, for the purpose of reinforcing and/or preserving the level of endogenous intracellular glutathione that gives the skin natural antioxidant protection.

The term "skin" means any cutaneous surface of the human body, including skin, mucous membranes and semi- mucous membranes, thus including the lips, the scalp and also the skin integuments, especially the nails, bodily hair and head hair.

According to the invention, a "physiologically acceptable medium" is either a medium that is cosmetically or pharmaceutically acceptable with the skin, mucous membranes, the nails and/or the hair, or a medium that can be administered orally.

Other subjects of the invention will be defined later in the rest of the description.

The dithiolane compounds in accordance with the present invention correspond to formula (I) below:

in which Y denotes O or NRi;

Ri denotes a hydrogen atom; a saturated linear Ci- C20 or branched C3-C20 or unsaturated C2-C20 alkyl hydrocarbon-based group; an aryl group optionally substituted with one or more hydroxyls and/or with one or more Ci-Cs alkoxy radicals;

R denotes a hydrogen atom; a saturated linear Ci- C20 or branched C3-C20 or unsaturated C2-C20 alkyl hydrocarbon-based group; a radical having the following formula :

in which n = 0, 1, 2, 3 or 4; x = 0, 1, 2 or 3 and

R3, which may be identical or different, denote a hydrogen atom or a linear or branched Ci-C₄ alkyl such as methyl, ethyl or isopropyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NRi and Ri is other than hydrogen, R and Ri may form a ring chosen from pyrrolidine, pyrroline, piperidine, piperazine, morpholine, thiomorpholine and azepine.

Preferentially, the alkoxy groups are linear Ci-C₄ groups and more preferentially methoxy, ethoxy, propoxy or butoxy and even more preferentially methoxy.

Preferentially, the hydrocarbon-based groups are linear or branched alkyls and may be chosen from: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl.

Preferentially, the aryl groups are phenyls.

More preferentially, the hydrocarbon-based groups are saturated linear or branched Ci-Cs alkyl radicals: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl.

The preferred compounds of formula (I) are those for which:

Ri denotes hydrogen or a saturated linear Ci-Cε or branched C3-C6 hydrocarbon-based group,

R denotes hydrogen or a saturated linear C1-C12 or branched C3-C12 hydrocarbon-based group; a saturated linear C1-C12 or branched C3-C12 hydrocarbon-based group; a radical having the following formula:

in which n = 0, 1, 2, 3 or 4; x = 0, 1, 2 or 3 and R3, which may be identical or different, denote hydrogen, methyl, ethyl or isopropyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NRi and Ri is other than hydrogen, R and Ri may form a ring chosen from pyrrolidine, pyrroline, piperidine, piperazine, morpholine, thiomorpholine and azepine .

Among these compounds, the ones that will more preferentially be used are those for which: R denotes hydrogen; a saturated linear C1-C10 or branched C3-C10 hydrocarbon-based group; a radical

in which n = 0, I or 2; x = 0, 1 or 2, and R3, which may be identical or different, denote hydrogen or methyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NRi and Ri is other than hydrogen, R and Ri may form a ring chosen from pyrrolidine, pyrroline, piperidine, piperazine, morpholine, thiomorpholine and azepine .

Among these compounds, the ones that will even more preferentially be used are those in which Y is NH.

As examples of compounds of formula (I), mention will be made particularly of the following compounds:

Synthesis

The compounds of formula (I) may be obtained according to the routes described below and documented in application EP 0 869 126 Al.

The compounds of formula (I) are obtained from 4- methyl-l,2-dithiolane-4-carboxylic acid (CAS: 208243- 72-5) or from the corresponding carboxamide via a Curtius or Hofmann rearrangement.

X OH CURTIUS RYH

S-S heating

HOFMANN

heating

Advantageously, the compound 4-methyl-l, 2-dithiolane-4- carboxylic acid (CAS: 208243-72-5) may be obtained according to the route described below starting with dichloropivalic acid according to a one-pot process, ending with a precipitation.

water/ reflux

Advantageously, the corresponding carboxamide compound may be obtained from 4 -methyl- 1, 2-dithiolane-4- carboxylic acid using isobutyl chloroformate or oxalyl chloride .

The Curtius reaction may be performed, for example, in an apolar aprotic solvent such as toluene or chloroform, or in a polar solvent such as acetonitrile, dimethylformamide or an alcohol (tBuOH, MeOH, EtOH) , in the presence of a source of azide ion (sodium azide, diphenylphosphoryl azide, trimethylsilyl azide) . Once the acyl azide intermediate has been formed, the reaction medium is heated in order to perform the rearrangement with extrusion of dinitrogen. The isocyanate thus formed is placed in contact with an alcohol or an amine to form carbamates or ureas.

The Hofmann rearrangement may be performed in polar protic solvents such as water or alcohols (tBuOH, MeOH, EtOH) or aprotic solvents such as dimethylformamide, in the presence of an oxidizing agent such as multivalent iodine derivatives (PIFA) or metal (sodium, calcium, etc.) hypochlorites.

Reference: Strategic application of named reactions in organic synthesis by L. Kurti and B. Czako, Elsevier Academic Press, 2005.

The Applicant has demonstrated that UV daylight (simulation of average UV daylight, L'Oreal concept, Christiaens F.J. et al . : Standard ultraviolet daylight for non-extreme exposure conditions, Photochem. Photobiol . , 2005) leads to a decrease in the level of intracellular GSH on HaCaT cells (keratinocytes obtained from an adult human skin implant spontaneously immortalized in vitro) . The depletion is maximal 6 hours after exposure (about 40% decrease) and return to the basal level occurs 24 hours after exposure to the UV daylight (UV-DL) .

The compounds according to the invention can prevent and/or correct this depletion of GSH, and can thus "boost" the endogenous antioxidant defence systems, so as to prepare the skin to better withstand

UV stress and to help it to repair itself. Their activity was compared with a reference compound, lipoic acid, which is known to increase the level of GSH.

The Applicant has thus shown that the capacity of the compounds according to the invention for increasing the level of GSH was much greater than that of lipoic acid, measured under the same conditions (see the example) .

A subject of the present invention is, in particular, the cosmetic use of at least one dithiolane compound chosen from those of formula (I) in a composition comprising a physiologically acceptable medium, for the purpose of reinforcing and/or preserving the level of endogenous intracellular glutathione that gives the skin natural antioxidant protection against oxidative stress caused especially by UV radiation.

Thus, the use according to the invention can reinforce and/or preserve the cellular antioxidant defence systems, in particular the antioxidant defence systems of skin cells. The skin cells are especially fibroblasts, keratinocytes and Langerhans cells.

According to one advantageous use of the invention, the compounds of general formula (I) are useful as skin photoprotective agents.

This use may be useful whether the skin has undergone exposure to daylight of an intensity lower than the minimum erythemal dose and whose effects do not produce visible signs on the skin, or whether the UV-ray damage is visible, for example by the appearance of redness on the skin.

Consequently, the impairments range from simple discomfort such as a uniquely perceptible sensation of heating of the skin, to redness, or even irritation.

Thus, the compounds of general formula (I) are useful for preventing and/or treating UV stress and/or heating sensations caused by solar radiation, in particular UVA and/or UVB.

The compounds of general formula (I) are also useful for preparing a composition, comprising a physiologically acceptable medium, intended for preventing and/or treating skin impairments, such as skin redness and irritation, caused by solar radiation.

The compounds of general formula (I) are also useful for the preparation of a composition, comprising a physiologically acceptable medium, for preventing and/or treating DNA lesions caused by solar radiation and thus for preventing the development of cancers, in particular skin cancers.

The compounds of general formula (I) are also useful for the preparation of a composition containing a physiologically acceptable medium, which is intended for treating skin and/or mucous membrane disorders induced by irradiation with UVA and/or UVB radiation.

Solar irradiation or exposure is characterized by an exposure to sunlight, and may especially be an intense irradiation corresponding to exposure to zenithal sunlight or to solar radiation varying by an angle of 30° around this zenithal position and/or when the skin is subjected to UV radiation capable of inducing a solar erythema (redness commonly known as "sunburn") , and defined by a minimum erythemal dose (MED) . This dose varies as a function of the phototype of the individual and of the UVA/UVB ratio.

The invention is especially directed towards preventing or reducing damage induced in the skin, mucous membranes and/or the integuments of a mammal, in particular of a human being, by short exposure to erythemal doses of solar radiation.

These solar exposure conditions comprise UVA and/or UVB rays, at doses around the MED, in particular at a dose of greater than or equal to 1 MED.

As explained above, by virtue of their capacity for increasing the level of GSH, the compounds of formula (I) according to the invention allow the establishment of the cutaneous antioxidant protective system.

Thus, the cosmetic use according to the invention of at least one dithiolane compound chosen from those of formula (I) in a composition containing a physiologically acceptable medium is particularly suitable for preparing the skin for exposure to sunlight .

In particular, preparation of the skin for exposure to sunlight may be performed by the daily application to the skin of the said cosmetic composition for one week, and preferably two weeks, before the exposure to sunlight, just up to at least one day (between 6 and 18 hours) before the exposure to sunlight .

Whether they are of endogenous or exogenous origin, free radicals cause substantial oxidative damage, especially in cell membranes (lipid peroxidation causing degradation of the membrane permeability) , cell nuclei (destruction of DNA) and tissues, in particular connective tissue (degradation of elastin and collagen fibres, and depolymerization of polyuronic fibres) . This damage especially leads to drying-out and loss of firmness and elasticity of the skin (Grinwald et al . 1980, Agren et al . 1997) .

Specialists currently consider that one of the causes of cellular ageing is the weakening of the defence capacities against free radicals and against the oxidation phenomena (especially the formation of superoxide ions) that they initiate.

Thus, more generally, the compounds of general formula (I) according to the invention are useful as indirect antioxidant compounds for preventing and/or limiting the formation of free radicals and/or for removing the free radicals present in cells, and may be used for any skin disorder caused by oxidative stress.

This activity of the compounds of general formula (I) is reinforced by the intrinsic antioxidant property of these compounds associated with their thiol funct i on .

Thus, the use of the compounds according to the invention allows certain clinical signs of ageing of the skin to be prevented and/or treated.

Ageing is a natural physiological phenomenon whose clinical signs may generally be reflected on the skin by the appearance of wrinkles and fine lines, by slackening of the cutaneous and subcutaneous tissues, by a loss of skin elasticity and by atony of the texture of the skin. The loss of firmness and tonicity of the skin, for instance wrinkles and fine lines, is at least partly accounted for by dermal atrophy and also flattening of the dermo-epidermal junction; the skin is less firm and more flaccid, and the thickness of the epidermis decreases.

Another clinical sign of ageing is the dry and coarse appearance of the skin, which is due essentially to greater desquamation; by diffracting light rays, these squamae also contribute towards the somewhat greyish appearance of the complexion.

Some of these signs are more particularly associated with intrinsic or physiological ageing, i.e. age-related ageing, whereas others are more specific to extrinsic ageing, i.e. ageing caused in general by the environment; this is more particularly a case of photo- ageing due to exposure to sunlight, light or any other radiation, or alternatively pollutants.

Thus, the subject of the invention is particularly suited towards the cosmetic use of at least one compound of general formula (I) according to the invention in a composition containing a physiologically acceptable medium, for preventing and/or treating loss of firmness and/or elasticity of the skin. Such a use especially allows the skin to regain a uniformly smooth appearance .

The invention is also suited to the cosmetic use of at least one compound of general formula (I) according to the invention in a composition containing a physiologically acceptable medium, for preventing and/or treating skin dehydration.

The subject of the invention is also more generally suited to the cosmetic use of at least one compound chosen from those of general formula (I) according to the invention in a composition containing a physiologically acceptable medium, for preventing and/or treating epidermal atrophy and/or skin roughness and/or skin dryness.

Another subject of the invention relates to the cosmetic use of at least one compound of general formula (I) in a composition containing a cosmetically acceptable medium, for preventing and/or treating the harmful effects of pollution on the skin.

It is known that the toxicity of atmospheric pollutants, especially gaseous pollutants such as sulfur dioxide, ozone and nitrogen oxides on the constituents of the skin (fibres, cells and enzymes) and on the sebum secreted by the skin is especially associated with their activity of free-radical initiators, which are a source of oxidation phenomena that cause cell damage in living beings.

The live cells, which are in direct and permanent contact with the external environment (especially the skin, the scalp and certain mucous membranes) , are particularly sensitive to these effects of gaseous pollutants, which are especially reflected by accelerated ageing of the skin, with early formation of wrinkles or fine lines, and also by a decrease in the vigour and dull appearance of the hair. As explained previously, an adverse effect of the presence of free radicals in the skin is that they cause peroxidation of lipids. With age (more particularly from the age of forty) , the accumulation of these peroxidized lipids is responsible for unpleasant body odour such as a rancid odour (Haze S. et al. J. Invest. Dermatol. 2001, 116 (4) : 520-4) .

The subject of the invention is suited to the cosmetic use of at least one compound of general formula (I) according to the invention in a composition containing a physiologically acceptable medium, for preventing and/or limiting and/or eliminating the peroxidation of skin lipids.

Thus, the subject of the invention is also useful for preventing and/or limiting and/or eliminating unpleasant body odour.

The compositions according to the invention may be intended for cosmetic and/or dermatological use. They may be compositions suitable for topical application, in particular external topical application to the skin, mucous membranes and/or the integuments.

According to another embodiment, the compositions according to the invention are suitable for the oral route, and are especially intended for oral cosmetic applications.

The amount of compound that may be used according to the invention obviously depends on the desired effect, and may thus vary within a wide range.

To give an order of magnitude, the compound (s) of formula (I) as defined previously may be used for the topical route, in particular the external topical route, in an amount representing from 0.001% to 20% of the total weight of the composition and preferentially in an amount representing from 0.01% to 10% of the total weight of the composition.

For the oral route, the compound (s) of formula (I) as defined previously may be used, the said compound being present in an amount of between 0.1 and 100 mg per dosage intake.

Formulation of the compositions

Preferably, the composition according to the invention comprising at least one compound of formula (I) is constituted of a cosmetically acceptable medium, i.e. a medium that has a pleasant colour, odour and feel and that does not cause any unacceptable discomfort .

The compositions are preferably cosmetic compositions or products. The term "cosmetic product" especially means any substance or preparation intended to be placed in contact with the various surface parts of the human body (epidermis, pilous and hair system, nails, lips and external genital organs) or with the teeth and the oral mucosae for the purpose, exclusively or mainly, for cleaning them, fragrancing them, modifying their appearance and/or correcting body odour and/or protecting them or keeping them in good condition (Amended Cosmetic Directive 76/768/EEC) .

The composition according to the invention may especially be in the form of an alcoholic, aqueous- alcoholic or oily solution, a suspension, a dispersion, a W/O, O/W or multiple emulsion, aqueous or anhydrous gels, or a vesicular dispersion of ionic or nonionic type. It may have a liquid, semi-liquid, pasty or solid consistency.

For topical application, the composition that may be used according to the invention may especially be in the form of an aqueous-alcoholic or oily solution or a dispersion of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersing a fatty phase in an aqueous phase (O/W) or conversely (W/O) or multiple emulsions, a free or compacted powder to be used in unmodified form or to be incorporated into a physiologically acceptable medium, or suspensions or emulsions of soft consistency of the aqueous or anhydrous cream or gel type, or alternatively microcapsules or microparticles, or vesicular dispersions of ionic and/or nonionic type. It may thus be in the form of an ointment, a tincture, a cream, a pomade, a powder, a patch, an impregnated pad, a solution, an emulsion or vesicular dispersion, a lotion, a gel, a spray, a suspension, a shampoo, an aerosol or a mousse. It may be anhydrous or aqueous. It may also consist of solid preparations constituting soaps or cleansing bars.

These compositions are prepared according to the usual methods .

According to another embodiment of the invention, the composition is suitable for oral use, in particular "cosmetic oral" use.

For oral use, the composition may especially be in the form of wafer capsules, gel capsules, coated tablets, granules, plain tablets, chewable pastes, gels or drinkable syrups or in any other form known to those skilled in the art.

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

Combinations The compositions according to the invention may also contain agents for reinforcing or complementing the activity of the compound of formula (I), and especially at least one compound chosen from antioxidants, antipollution agents, organic screening agents and/or mineral screening agents, and agents for stimulating DNA repair.

The compounds of formula (I) according to the invention may also be advantageously combined with extracts (total biomass, culture medium, ribosomal fraction, cell membrane fraction, LPS fraction, lipid A, etc.) of non-fruiting, non-photosynthetic filamentous bacteria such as Vitreoscilla filiformis or alternatively {2- (acetyl (3-trifluoromethylphenyl) - amino] -3-methylbutyrylamino } acetic acid.

It is thus possible, for example, to use an antioxidant chosen from: - vitamin E (tocopherol) and derivatives thereof, including the acetate, linoleate or nicotinate, preferably at concentrations of about from 0.1% to 5%, γ-orizanol (0.1% to 5%), lysine pidolate or arginine pidolate (0.5% to 10%), plant extracts such as extract of balm (0.01% to 2%), extract of silymarin (0.01% to 2%), extract of Ginkgo biloba (0.05% to 2%), extract of sage (0.05% to 2%), extract of cola nuts (0.05% to 2%), extract of rutin (0.1% to 2%) or extract of thyme (0.1% to 2%), the percentages being given as dry matter, carotenoids, such as CC- and β-carotene or lycopene in a purified form or in an extract (for example tomato puree with a lycopene titre reaching a final lycopene concentration of between 10^~12% to 10% and more preferentially from 10^~7% to 0.1%), proanthocyanidol oligomers from pine, hawthorn or grape (0.1% to 2%) , di-tert-butylhydroxybenzylidenecamphor (0.1% to Z 9S-S.\j , green tea (0.1% to 2%),

- caffeine (0.1% to 5%) , - glycerol (2% to 30%),

- mannitol (2% to 30%) , carnosine (0.1% to 2%),

- superoxide dismutase (100 to 10 000 IU/ 100 g) , guanosine (0.01% to 1%), - microalgae containing ethoxyquine such as Hematococcus (0.005% to 1%), pentasodium aminotrimethylenephosphonate (0.001% to 0.5%) ,

- lactoperoxidase (0.01% to 0.1%), - vitamin C and derivatives thereof,

- lactoferrin (0.01% to 0.1%), isopropyl (benzyl { 2- [benzyl (2-isopropoxy-2-oxo- ethyl) amino] ethyl } amino) acetate, phloretin, - hesperidin, neohesperidin dihydrochalcone, ferulic acid,

- Eukarions (including EUK-8, EUK-134 and EUK-189 developed by Proteome Systems) , - L-2-oxo-4-thiazolidinecarboxylic acid ergothioneine, caffeic acid,

Desferal,

4, 4' - (2, 3-dimethylbutane-l, 4-diyl) dibenzene- 1,2-diol.

A mixture of several antioxidants may also be used.

Mention may also be made of free-radical scavengers, in particular bioflavonoids; coenzyme QlO or ubiquinone; certain enzymes such as catalase, glutathione peroxidase and quinone reductases; glutathione; benzylidenecamphor; benzylcyclanones; substituted naphthalenones; pidolates; phytanetriol; lignans; melatonin; hydroxylated chalcones, and also reduced derivatives thereof.

Preferably, the antioxidant is chosen from vitamin C, vitamin E, isopropyl (benzyl { 2- [benzyl (2-isopropoxy- 2-oxoethyl) amino] ethyl } amino) acetate, ferulic acid, phloretin, neohesperidin dihydrochalcone and SOD.

The term "anti-pollution agent" means any compound capable of trapping ozone, monocyclic or polycyclic aromatic compounds such as benzpyrene and/or heavy metals such as cobalt, mercury, cadmium and/or nickel. The term "free-radical scavenger" means any compound capable of trapping free radicals.

As ozone-trapping agents that may be used in the composition according to the invention, mention may be made in particular of vitamin C and its derivatives including ascorbyl glucoside; phenols and polyphenols, in particular tannins, ellagic acid and tannic acid; epigallocatechin and natural extracts containing it; extracts of olive tree leaf; extracts of tea, in particular of green tea; anthocyans; extracts of rosemary; phenol acids, in particular chorogenic acid; stilbenes, in particular resveratrol; sulfur-containing amino acid derivatives, in particular S-carboxy- methylcysteine; ergothioneine; N-acetylcysteine; chelating agents, for instance N, N' -bis (3, 4, 5-tri- methoxybenzyl) ethylenediamine or one of its salts, metal complexes or esters; carotenoids such as crocetin; and various starting materials, for instance the mixture of arginine, histidine ribonucleate, mannitol, adenosine triphosphate, pyridoxine, phenylalanine, tyrosine and hydrolysed RNA, sold by Laboratoires Serobiologiques under the trade name CPP LS 2633-12F®, the water-soluble fraction of corn sold by the company Solabia under the trade name Phytovityl®, the mixture of extract of fumitory and of extract of lemon sold under the name Unicotrozon C-49® by the company Induchem, and the mixture of extracts of ginseng, of apple, of peach, of wheat and of barley, sold by the company Provital under the trade name Pronalen Bioprotect®.

As agents for trapping monocyclic or polycyclic aromatic compounds, which may be used in the composition according to the invention, mention may be made in particular of tannins such as ellagic acid; indole derivatives, in particular 3-indolecarbinol; extracts of tea, in particular of green tea, extracts of water hyacinth or Eichornia crassipes; and the water-soluble fraction of corn sold by the company Solabia under the trade name Phytovityl®.

Finally, as heavy-metal-trapping agents that may be used in the composition according to the invention, mention may be made in particular of chelating agents such as EDTA, the pentasodium salt of ethylenediaminetetramethylenephosphonic acid, and N, N'- bis (3, 4 , 5-trimethoxybenzyl) ethylenediamine or one of the salts, metal complexes or esters thereof; phytic acid; chitosan derivatives; extracts of tea, in particular of green tea; tannins such as ellagic acid; sulfur-containing amino acids such as cysteine; extracts of water hyacinth (Eichornia crassipes) ; and the water-soluble fraction of corn sold by the company Solabia under the trade name Phytovityl®.

Advantageously, the compositions according to the invention contain at least one organic photoprotective agent and/or at least one mineral photoprotective agent that is active in the UVA and/or UVB range (absorbers) , and that is water-soluble, liposoluble or insoluble in the commonly used cosmetic solvents. Preferably, a system for screening out both UVA radiation and UVB radiation will preferably be used. Sunscreens are molecules that absorb UV radiation and thus prevent it from reaching the skin cells. They can absorb either mainly UVB or mainly UVA, depending on their nature. There are two major categories of sunscreens, either organic, or mineral (zinc oxide or titanium oxide) . By using them in cosmetic compositions in combination and in a sufficient amount, they can block a large proportion of the UV radiation.

However, it is commonly accepted that, in order to be effective, these formulations must be used under good application conditions (sufficient amount, frequent renewal and uniform spreading) . These application conditions are not always adhered to by the user, which increases the risk of an appreciable amount of UV radiation reaching the skin cells, and thus of giving rise to the biological effects mentioned above. Furthermore, in order to obtain absorption with respect to all the wavelengths of the UVB + UVA solar UV spectrum, several molecules that absorb in complementary wavelength ranges need to be combined.

The additional organic screening agents are chosen especially from anthranilates; cinnamic derivatives; salicylic derivatives; camphor derivatives; benzophenone derivatives; β, β-diphenylacrylate derivatives; triazine derivatives; benzotriazole derivatives; benzalmalonate derivatives, especially those mentioned in patent US 5 624 663; benzimidazole derivatives; imidazolines; bis-benzazolyl derivatives as described in patents EP 669 323 and US 2 463 264; p- aminobenzoic acid (PABA) derivatives; methylenebis- (hydroxyphenylbenzotriazole) derivatives as described in patent applications US 5 237 071, US 5 166 355, GB 2 303 549, DE 197 26 184 and EP 893 119; benzoxazole derivatives as described in patent applications EP 0 832 642, EP 1 027 883, EP 1 300 137 and DE 101 62 844; screening polymers and screening silicones such as those described especially in patent application WO 93/04665; α-alkylstyrene-based dimers, such as those described in patent application DE 198 55 649; 4, 4-diarylbutadienes such as those described in patent applications EP 0 967 200, DE 197 46 654, DE 197 55 649, EP-A-I 008 586, EP 1 133 980 and EP 133 981; merocyanin derivatives such as those described in patent applications WO 04/006 878, WO 05/058 269 and WO 06/032 741; and mixtures thereof.

As examples of additional organic photoprotective agents, mention may be made of those denoted hereinbelow under their INCI name: Cinnamic derivatives:

Ethylhexyl methoxycinnamate sold in particular under the trade name Parsol MCX by DSM Nutritional Products, Inc . ,

Isopropyl methoxycinnamate,

Isoamyl methoxycinnamate sold under the trade name Neo Heliopan E 1000 by Symrise, DEA methoxycinnamate,

Diisopropyl methylcinnamate,

Glyceryl ethylhexanoate dimethoxycinnamate; para-Aminobenzoic acid derivatives: PABA, Ethyl PABA,

Ethyl dihydroxypropyl PABA,

Ethylhexyl dimethyl PABA sold in particular under the name Escalol 507 by ISP,

Glyceryl PABA, PEG-25 PABA sold under the name Uvinul P25 by BASF;

Salicylic derivatives:

Homosalate sold under the name Eusolex HMS by Rona/EM Industries, Ethylhexyl salicylate sold under the name Neo Heliopan OS by Symrise,

Dipropylene glycol salicylate sold under the name Dipsal by Scher, TEA salicylate sold under the name Neo Heliopan TS by Symrise; β, β-Diphenylacrylate derivatives :

Octocrylene sold in particular under the trade name Uvinul N539 by BASF,

Etocrylene sold in particular under the trade name Uvinul N35 by BASF;

Benzophenone derivatives:

Benzophenone-1 sold under the trade name Uvinul 400 by BASF,

Benzophenone-2 sold under the trade name Uvinul D50 by BASF,

Benzophenone-3 or Oxybenzone sold under the trade name Uvinul M40 by BASF, Benzophenone-4 sold under the trade name Uvinul MS40 by BASF,

Benzophenone-5,

Benzophenone-6 sold under the trade name Helisorb 11 by Norquay, Benzophenone-8 sold under the trade name Spectra- Sorb UV-24 by American Cyanamid,

Benzophenone-9 sold under the trade name Uvinul DS-49 by BASF,

Benzophenone- 12 n-hexyl 2- (4-diethylamino-2-hydroxybenzoyl) - benzoate sold under the trade name Uvinul A+ by BASF;

Benzylidenecamphor derivatives:

3-Benzylidenecamphor manufactured under the name Mexoryl SD by Chimex, 4-Methylbenzylidenecamphor sold under the name Eusolex 6300 by Merck,

Benzylidenecamphorsulfonic acid manufactured under the name Mexoryl SL by Chimex,

Camphor benzalkonium methosulfate manufactured under the name Mexoryl SO by Chimex,

Terephthalylidenedicamphorsulfonic acid manufactured under the name Mexoryl SX by Chimex,

Polyacrylamidomethylbenzylidenecamphor manufactured under the name Mexoryl SW by Chimex; Phenylbenzimidazole derivatives:

Phenylbenzimidazolesulfonic acid sold in particular under the trade name Eusolex 232 by Merck,

Disodium phenyl dibenzimidazole tetrasulfonate sold under the trade name Neo Heliopan AP by Symrise;

Phenylbenzotriazole derivatives:

Drometrizole trisiloxane sold under the name Silatrizole by Rhodia Chimie,

Methylenebis (benzotriazolyl) tetramethylbutylphenol sold in solid form under the trade name MIXXIM BB/100 by Fairmount Chemical, or in micronized form as an aqueous dispersion under the trade name Tinosorb M by Ciba Specialty Chemicals;

Triazine derivatives: Bis (ethylhexyloxyphenol) methoxyphenyltriazine sold under the trade name Tinosorb S by Ciba Geigy, Ethylhexyltriazone sold in particular under the trade name Uvinul T150 by BASF,

Diethylhexylbutamidotriazone sold under the trade name Uvasorb HEB by Sigma 3V,

2,4, 6-tris (diisobutyl 4' -aminobenzalmalonate) -s- triazine,

2,4, 6-tris (dineopentyl 4' -aminobenzalmalonate) -s- triazine, 2, 4-bis (n-butyl 4 ' -aminobenzoate) -6- (aminopropyl- trisiloxane) -s-triazine,

2, 4-bis (dineopentyl 4' -aminobenzalmalonate) -6- (n- butyl 4' -aminobenzoate) -s-triazine, the symmetrical triazine screening agents described in patent US 6 225 467, patent application WO 2004/085 412 (see compounds 6 and 9) or the document Symmetrical Triazine Derivatives IP.COM Journal, IP.COM INC West Henrietta, NY, US (20 September 2004), especially 2, 4, 6-tris (biphenyl) -1, 3, 5-triazines (in particular 2, 4, 6-tris (biphenyl-4-yl-l, 3, 5-triazine) and 2, 4, 6-tris (terphenyl) -1, 3, 5-triazine which is also mentioned in patent applications WO 06/035 000, WO 06/034 982, WO 06/034 991, WO 06/035 007, WO 2006/034 992 and WO 2006/034 985; Anthranilic derivatives:

Menthyl anthranilate sold under the trade name Neo Heliopan MA by Haarmann and Reimer;

Imidazoline derivatives: Ethylhexyldimethoxybenzylidenedioxoimidazoline propionate;

Benzalmalonate derivatives:

Polyorganosiloxane containing benzalmalonate functions, for instance Polysilicone-15, sold under the trade name Parsol SLX by DSM Nutritional Products, Inc.;

4, 4-Diarylbutadiene derivatives:

1, 1-Dicarboxy (2,2' -dimethylpropyl) -4, 4-diphenyl- butadiene;

Benzoxazole derivatives: 2, 4-bis [5- (l-dimethylpropyl)benzoxazol-2-yl (4-phenyl) - imino] -6- (2-ethylhexyl) imino-1, 3, 5-triazine sold under the name Uvasorb K2A by Sigma 3V;

Merocyanin derivatives

Octyl 5-N, N-diethylamino-2-phenylsulfonyl-2, 4- pentadienoate; and mixtures thereof.

The preferential organic screening agents are chosen from: Ethylhexyl methoxycinnamate,

Ethylhexyl salicylate,

Homosalate,

Octocrylene,

Phenylbenzimidazolesulfonic acid, Benzophenone-3,

Benzophenone-4,

Benzophenone-5, n-Hexyl 2- (4-diethylamino-2-hydroxybenzoyl) - benzoate, 4-Methylbenzylidenecamphor,

Terephthalylidenedicamphorsulfonic acid,

Disodium phenyldibenzimidazoletetrasulfonate, Methylenebis (benzotriazolyl) tetramethylbutyl- phenol,

Bis (ethylhexyloxyphenol) methoxyphenyltriazine,

Ethylhexyltriazone, Diethylhexylbutamidotriazone,

2,4, 6-Tris (dineopentyl 4' -aminobenzalmalonate) -s- triazine,

2,4, 6-Tris (diisobutyl 4' -aminobenzalmalonate) -s- triazine, 2, 4-Bis (n-butyl 4' -aminobenzoate) -6- (aminopropyl- trisiloxane) -s-triazine,

2, 4-Bis (dineopentyl 4' -aminobenzalmalonate) -6- (n- butyl 4' -aminobenzoate) -s-triazine,

2,4, 6-Tris (biρhenyl-4-yl) -1, 3, 5-triazine, 2,4, 6-Tris (terphenyl) -1, 3, 5-triazine,

Drometrizole trisiloxane,

Polysilicone-15,

1, 1-Dicarboxy (2,2' -dimethylpropyl) -4, 4-diphenyl- butadiene, 2, 4-Bis [5-1 (dimethylpropyl) benzoxazol-2-yl (4-phenyl) - imino] -6- (2-ethylhexyl) imino-1, 3, 5-triazine,

Octyl 5-N, N-diethylamino-2-phenylsulfonyl-2 , 4- pentadienoate, and mixtures thereof.

The organic screening agents in accordance with the invention generally represent from 0.1% to 30% and preferably from 1% to 25% of the total weight of the composition .

The additional mineral UV screening agents used in accordance with the present invention are metal oxide pigments. More preferentially, the mineral UV screening agents of the invention are metal oxide particles with a mean elementary particle size of less than or equal to 500 nm, more preferentially between 5 nm and 500 nm, even more preferentially between 10 nm and 100 nm and preferentially between 15 nm and 50 nm. They may be chosen especially from titanium, zinc, iron, zirconium or cerium oxides or mixtures thereof, and more particularly titanium oxides.

Such coated or uncoated metal oxide pigments are described in particular in patent application EP-A- 0 518 773. Commercial pigments that may be mentioned include the products sold by companies Kemira, Tayca, Merck and Degussa.

The metal oxide pigments may be coated or uncoated.

The coated pigments are pigments that have undergone one or more surface treatments of chemical, electronic, mechanochemical and/or mechanical nature with compounds such as amino acids, beeswax, fatty acids, fatty alcohols, anionic surfactants, lecithins, sodium, potassium, zinc, iron or aluminium salts of fatty acids, metal alkoxides (of titanium or of aluminium) , polyethylene, silicones, proteins

(collagen, elastin) , alkanolamines, silicon oxides, metal oxides or sodium hexametaphosphate .

The coated pigments are more particularly titanium oxides that have been coated:

- with silica, such as the product Sunveil from the company Ikeda,

- with silica and iron oxide, such as the product Sunveil F from the company Ikeda,

- with silica and alumina, such as the products Microtitanium Dioxide MT 500 SA and Microtitanium Dioxide MT 100 SA from the company Tayca, Tioveil from the company Tioxide, - with alumina, such as the products Tipaque TTO- 55 (B) and Tipaque TTO-55 (A) from the company Ishihara and UVT 14/4 from the company Kemira,

- with alumina and aluminium stearate, such as the product Microtitanium Dioxide MT 100 TV, MT 100 TX, MT 100 Z and MT-Ol from the company Tayca, and the products Solaveil CT-IO W and Solaveil CT 100 from the company Uniqema, and the product Eusolex T-AVO from the company Merck, - with silica, alumina and alginic acid, such as the product MT-100 AQ from the company Tayca,

- with alumina and aluminium laurate, such as the product Microtitanium Dioxide MT 100 S from the company Tayca, - with iron oxide and iron stearate, such as the product Microtitanium Dioxide MT 100 F from the company Tayca,

- with zinc oxide and zinc stearate, such as the product BR 351 from the company Tayca, - with silica and alumina and treated with a silicone, such as the products Microtitanium Dioxide MT 600 SAS, Microtitanium Dioxide MT 500 SAS or Microtitanium Dioxide MT 100 SAS from the company Tayca, - with silica, alumina and aluminium stearate and treated with a silicone, such as the product STT-30-DS from the company Titan Kogyo,

- with silica and treated with a silicone, such as the product UV-Titan X 195 from the company Kemira, - with alumina and treated with a silicone, such as the products Tipaque TTO-55 (S) from the company Ishihara or UV Titan M 262 from the company Kemira,

- with triethanolamine, such as the product STT- 65-S from the company Titan Kogyo, - with stearic acid, such as the product Tipaque

TTO-55 (C) from the company Ishihara, with sodium hexametaphosphate, such as the product Microtitanium Dioxide MT 150 W from the company

Tayca, - Tiθ2 treated with octyltrimethylsilane, sold under the trade name T 805 by the company Degussa

Silices,

- Tiθ2 treated with a polydimethylsiloxane, sold under the trade name 70250 Cardre UF TiO2SI3 by the company Cardre, anatase/rutile Tiθ2 treated with a polydimethylhydrogenosiloxane, sold under the trade name Microtitanium Dioxide USP Grade Hydrophobic by the company Color Techniques.

The uncoated titanium oxide pigments are sold, for example, by the company Tayca under the trade names Microtitanium Dioxide MT 500 B or Microtitanium Dioxide MT 600 B, by the company Degussa under the name P 25, by the company Wackher under the name Transparent titanium oxide PW, by the company Miyoshi Kasei under the name UFTR, by the company Tomen under the name ITS and by the company Tioxide under the name Tioveil AQ.

The uncoated zinc oxide pigments are, for example:

- those sold under the name Z-Cote by the company Sunsmart ;

- those sold under the name Nanox by the company Elementis;

- those sold under the name Nanogard WCD 2025 by the company Nanophase Technologies.

The coated zinc oxide pigments are, for example: - those sold under the name Zinc Oxide CS-5 by the company Toshibi (ZnO coated with polymethylhydrogeno- siloxane) ;

- those sold under the name Nanogard Zinc Oxide FN by the company Nanophase Technologies (as a 40% dispersion in Finsolv TN, C12-C15 alkyl benzoate) ;

- those sold under the name Daitopersion ZN-30 and Daitopersion ZN-50 by the company Daito (dispersions in cyclopolymethylsiloxane/oxyethylenated polydimethyl- siloxane, containing 30% or 50% of nanozinc oxides coated with silica and polymethylhydrogenosiloxane) ;

- those sold under the name NFD Ultrafine ZnO by the company Daikin (ZnO coated with perfluoroalkyl phosphate and copolymer based on perfluoroalkylethyl as a dispersion in cyclopentasiloxane) ; - those sold under the name SPD-Zl by the company Shin-Etsu (ZnO coated with silicone-grafted acrylic polymer, dispersed in cyclodimethylsiloxane) ;

- those sold under the name Escalol ZlOO by the company ISP (alumina-treated ZnO dispersed in an ethylhexyl methoxycinnamate/PVP-hexadecene/methicone copolymer mixture) ;

- those sold under the name Fuji ZnO-SMS-IO by the company Fuji Pigment (ZnO coated with silica and polymethylsilsesquioxane) ;

- those sold under the name Nanox Gel TN by the company Elementis (ZnO dispersed at a concentration of 55% in C12-C15 alkyl benzoate with hydroxystearic acid polycondensate) .

The uncoated cerium oxide pigments are sold under the name Colloidal Cerium Oxide by the company Rhone- Poulenc .

The uncoated iron oxide pigments are sold, for example, by the company Arnaud under the names Nanogard WCD 2002 (FE 45B), Nanogard Iron FE 45 BL AQ, Nanogard FE 45R AQ and Nanogard WCD 2006 (FE 45R) or by the company Mitsubishi under the name TY-220,

The coated iron oxide pigments are sold, for example, by the company Arnaud under the names Nanogard WCD 2008 (FE 45B FN), Nanogard WCD 2009 (FE 45B 556), Nanogard FE 45 BL 345 and Nanogard FE 45 BL or by the company BASF under the name Transparent Iron Oxide.

Mention may also be made of mixtures of metal oxides, especially of titanium dioxide and of cerium dioxide, including the silica-coated equal-weight mixture of titanium dioxide and of cerium dioxide, sold by the company Ikeda under the name Sunveil A, and also the alumina, silica and silicone-coated mixture of titanium dioxide and of zinc dioxide, such as the product M 261 sold by the company Kemira, or the alumina, silica and glycerol-coated mixture of titanium dioxide and of zinc dioxide, such as the product M 211 sold by the company Kemira.

According to the invention, coated or uncoated titanium oxide pigments are particularly preferred.

The mineral screening agents in accordance with the invention generally represent from 0.5% to 40% and preferably from 1% to 30% of the total weight of the composition .

The mineral screening agents may be introduced into the compositions according to the invention in their native form or in the form of a pigmentary paste, i.e. as a mixture with dispersants, as described, for example, in document GB-A-2 206 339.

A vitamin E derivative that may especially be used is tocopheryl acetate.

The agents for stimulating DNA repair are especially enzymes that promote its repair, such as photolyase and/or endonuclease T4.

The composition may also contain moisturizers, NO- synthase inhibitors, free-radical scavengers or agents for stimulating the synthesis of epidermal macromolecules and/or for preventing their degradation.

The amounts of these various components will be adapted by a person skilled in the art.

The examples that follow serve to illustrate the invention. In the formulation examples, the amounts of the composition ingredients are given as weight percentages relative to the total weight of the composition . Examples of synthesis :

Example 1: Synthesis of the compound N, N' -bis (4-methyl- 1 , 2-dithiolan-4-yl) urea (compound 2)

1.1 equivalents of triethylamine (306 μl) and 1.2 equivalents (520 μl) of diphenylphosphoryl azide are added to 2 mmol (330 mg) of 4 -methyl- 1, 2-dithiolane-4- carboxylic acid in 10 ml of tBuOH. The reaction medium is stirred at 20⁰C for 10 minutes and then refluxed until the evolution of gas has ceased. After concentrating under vacuum, the crude product is subjected to purification on a column of silica (eluent: 100/0 to 90/10 dichloromethane/methanol) to give, after concentrating the desired fractions on a rotavapor (P = 100 mbar, T = 40⁰C), a pale yellow solid corresponding to the expected product.

NMR and mass spectrum in accordance with the expected product .

Example 2: Synthesis of the compound tert-butyl 4- methyl-1 , 2-dithiolan-4-yl carbamate (compound 3)

Same synthetic conditions as for Example 1 with anhydrous tBuOH, under nitrogen and in the presence of a molecular sieve. A yellow wax corresponding to the tert-butyl carbamate is obtained. NMR and mass spectrum in accordance with the expected product .

Example 3: Synthesis of the compound N-benzyl-N' - (4- methyl-1 , 2-dithiolan-4-yl) urea (compound 1)

Same conditions as for Example 2, but using toluene as solvent and adding 218 μl of benzylamine after the evolution of gas has ceased, at room temperature. The reaction medium is diluted with a basic solution and the organic phase is then washed with an acidic solution. The dried organic phase is then concentrated under vacuum to give a paste, which is taken up in ether to give an orange solid identified as N-benzyl- N' - (4 -methyl- 1, 2-dithiolan-4-yl) urea .

NMR and mass spectrum in accordance with the expected product .

Example 4 : measurement of the activity of the compounds according to the invention towards increasing the level of GSH

The study consisted in evaluating at the cellular level the protective effect of the reference molecule, lipoic acid, and also of lipoic acid derivatives according to the invention, with respect to the UV-DL- induced depletion of intracellular GSH.

To do this, HaCaT cells were exposed to UV daylight (UV-DL) . The level of intracellular GSH was then measured, thus allowing evaluation of the possible protection afforded by the addition to the culture medium of the lipoic acid derivatives according to the invention .

UV daylight corresponds to the radiation of non- zenithal sunlight and to an average spectral illumination: it stimulates the radiation received by the skin of an individual in the course of a day and not solely to that corresponding to exposure to zenithal sunlight. Devices for reproducing this radiation are described in FR 2 863 356. The evaluation technique uses a fluorescent probe, monochlorobimane (MCB) . MCB has the particular feature of having, unlike other bimane compounds such as monobromobimane, more selective reactivity towards glutathione: the blue fluorescent compound measured (GSH-monochlorobimane) results from an enzymatic reaction catalysed by glutathione-S-transferase . The specificity of MCB towards GSH in our keratinocyte model (HaCaT line) was confirmed previously. Pretreatment of cells with the reference molecule, lipoic acid, for 24 hours at 1 mM affords approximately 100% protection against the UV- DL-induced depletion of GSH (see Figure 1 showing the evaluation of the protective effect of lipoic acid at

1 mM in the MCB test on HaCaT: the measurement of the level of intracellular GSH is performed on keratinocytes that are or are not pretreated with lipoic acid at 1 mM and exposed to UV-DL at t = 0, t = 6 hours and t = 24 hours after the exposure to UV-DL) ; this protection is about 83% at 500 μM and about 10% at 100 μM.

The compound N, N ' -bis (4 -methyl- 1, 2-dithiolan-4- yl)urea (compound 2) according to the invention was tested. Evaluation of the protective effect of compound

2 at 30 μM is performed in the MCB test on HaCaT: evaluation of the protective effect of the silyl dithiolane compounds of patent application WO 2008/058 999 at 100 μM is also performed in the MCB test on HaCaT: the compound 5- (1, 2-dithiolan-3-yl) -N- [3- (trimethylsilyl) propyl] pentanamide and the compound ( trimethylsilyl) methyl 5- ( 1 , 2 -dithiolan-3- yl) pentanoate . Measurement of the intracellular level of GSH is performed on keratinocytes that have or have not been pretreated with the active agents and exposed to UV-DL, t = 6 hours after the exposure to UV-DL) . The results are given in the graphs in Figures 2 and 3.

It is seen that the protection afforded by this active agent with respect to UV daylight-induced depletion of GSH is higher than that for the reference molecule, lipoic acid at 100 μM as well as for the compounds of the prior art, this superiority occurring as low as 30 μM (see Figures 2 and 3) . Example 5: antisun composition (oil-in-water emulsion)

^■ Compound of Example 1, 2 or 3 3 g

^■ 80/20 mixture of cetylstearyl alcohol and 3 g of oxyethylenated cetylstearyl alcohol

(33 EO units) sold by the company Tensia under the trade name Dehsconet® 390

^■ Glyceryl mono- and distearate mixture 2 g sold under the trade name Cerasynth® SD by the company ISP

^■ Cetyl alcohol 1.5 g

^■ Polydimethylsiloxane sold under the name 1.5 g DC200 Fluid® by the company Dow Corning

^■ Glycerol 15 g

^■ Parleam = hydrogenated isoparaffin 20 g (6-8 mol of isobutylene) by the company

NOF Corporation

^■ Preserving agents qs

^■ Demineralized water qs 77 g

The fatty phase containing the compound is heated at about 70 - 80⁰C until completely melted. The water is then added in a single portion at 80⁰C with vigorous stirring. Stirring is continued for 10 to 15 minutes, the mixture is then allowed to cool with moderate stirring to about 40⁰C and the preserving agents are added.

Example 6: antisun composition (oil-in-water emulsion)

^■ Compound of Example 1, 2 or 3 2 g

(33 EO units) sold by the company Tensia under the trade name Dehsconet® 390

^■ Cetyl alcohol 2.5 g

^■ C12-C15 alkyl benzoate sold under the trade 20 g name Finsolv TN by Witco

^■ Glycerol 15 g

^■ Preserving agents qs

^■ Demineralized water qs 97 g

This cream is prepared according to the standard techniques for preparing emulsions by dissolving the screening agent in the fatty phase containing the emulsifiers, heating this fatty phase to 70-80⁰C and adding, with vigorous stirring, the water heated to the same temperature. Stirring is continued for 10 to

15 minutes and the mixture is then allowed to cool with moderate stirring, and the fragrance and preserving agent are finally added at about 40⁰C.

Claims

1. Dithiolane compound of formula (I) below:

in which Y denotes O or NRi;

Ri denotes a hydrogen atom; a saturated linear Ci-

C20 or branched C3-C20 or unsaturated C2-C20 alkyl hydrocarbon-based group; an aryl group optionally substituted with one or more hydroxyls and/or with one or more Ci-Cs alkoxy radicals;

in which n = 0, 1, 2, 3 or 4; x = 0, 1, 2 or 3 and R3, which may be identical or different, denote a hydrogen atom or a linear or branched C₁-C₄ alkyl such as methyl, ethyl or isopropyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NHRi and Ri is other than hydrogen, R and Ri may form a ring chosen from pyrrolidine, pyrroline, piperidine, piperazine, morpholine, thiomorpholine and azepine.

2. Dithiolane compound according to Claim 1, in which:

in which n = 0, 1, 2, 3 or 4; x = 0, 1, 2 or 3 and R3, which may be identical or different, denote hydrogen, methyl, ethyl or isopropyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NHRi and Ri is other than hydrogen, R and Ri may form a ring chosen from pyrrolidine, pyrroline, piperidine, piperazine, morpholine, thiomorpholine and azepine .

3. Dithiolane compound according to Claim 2, in which: R denotes hydrogen; a saturated linear C1-C10 or branched C3-C10 hydrocarbon-based group; a radical

in which n = 0, I or 2; x = 0, I or 2 and R3, which may be identical or different, denote hydrogen or methyl; the radical 4-methyl dithiolane when Y denotes NH; when Y denotes NHRi and Ri is other than hydrogen, R and Ri may form a ring chosen from pyrrolidine, pyrroline, piperidine, piperazine, morpholine, thiomorpholine and azepine .

4. Dithiolane compound according to Claim 3, in which Y is NH.

5. Dithiolane compound according to any one of Claims 1 to 4, chosen from the following compounds:

6. Cosmetic or pharmaceutical composition comprising, in a physiologically acceptable medium, at least one dithiolane compound of formula (I) according to any one of Claims 1 to 5.

7. Cosmetic use of at least one dithiolane compound of formula (I) according to any one of Claims 1 to 5 in a composition comprising a physiologically acceptable medium, for the purpose of reinforcing and/or preserving the skin's natural antioxidant protection against oxidative stress caused especially by UV radiation.

8. Use according to Claim 7, for the purpose of preparing skin for exposure to sunlight.

9. Use according to Claim 7 or 8, for the purpose of preventing and/or treating the signs of ageing of the skin, especially:

(i) loss of firmness and/or elasticity and/or tonicity of the skin;

(ii) the dry and coarse appearance of the skin; (iii) skin dehydration; (iv) epidermal atrophy and/or skin roughness and/or skin dryness.

10. Use according to any one of Claims 7 to 9, for the purpose of preventing and/or treating the harmful effects of pollution on the skin.

11. Use according to any one of Claims 7 to 10, characterized in that the composition is for external topical use or for oral use.

12. Cosmetic process for preparing the skin to receive sunlight, comprising at least one step of administering at least one compound according to any one of Claims 1 to 5.