WO2019120830A1

WO2019120830A1 - Ascorbic 3-xyloside derivatives for cosmetic use thereof

Info

Publication number: WO2019120830A1
Application number: PCT/EP2018/081949
Authority: WO
Inventors: Xavier Marat; Maria Dalko
Original assignee: L'oreal
Priority date: 2017-12-21
Filing date: 2018-11-20
Publication date: 2019-06-27
Also published as: FR3075797A1; FR3075797B1

Abstract

The invention relates to ascorbic 3-xyloside derivative compounds of formula (I) and also the salts thereof, the solvates thereof and the optical isomers thereof, the geometric isomers thereof, the tautomers thereof, and/or the racemic mixtures thereof, alone or as a mixture. The invention also relates to a process for non-therapeutic cosmetic treatment of keratin materials, such as the skin, in particular a cosmetic process for depigmenting, lightening and/or bleaching keratin materials, in particular the skin, using these compounds (I)..

Description

ASCORBIC 3-XYLOSIDE DERIVATIVES

FOR COSMETIC USE THEREOF

The present invention relates to novel ascorbic 3-xyloside derivative compounds, to the non-therapeutic cosmetic use thereof, and to the compositions, in particular the cosmetic competitions, which contain them.

In one particular embodiment, the present invention relates to the non- therapeutic cosmetic use of novel ascorbic 3-xyloside derivative compounds for depigmenting and/or bleaching keratin materials and in particular the skin.

In another particular embodiment, the present invention also relates to the non-therapeutic cosmetic use of novel ascorbic 3-xyloside derivative compounds for combating the ageing of keratin materials, in particular skin ageing.

At various periods in their life, some people develop darker and/or more coloured blemishes on the skin, and more especially on the hands and the face, which give the skin heterogeneity. These blemishes are especially due to a high concentration of melanin in the keratinocytes located at the surface of the skin.

The use of highly effective inoffensive topical depigmenting substances is most particularly sought for the purpose of treating and/or reducing pigmentary blemishes.

The mechanism of formation of the pigmentation of the skin, i.e. of the formation of melanin, is particularly complex and involves, schematically, the following main steps:

Tyrosine ® Dopa ® Dopaquinone ® Dopachrome ® Melanin

Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1 .14.18.1 ) is the essential enzyme involved in this sequence of reactions. In particular, it catalyzes the conversion reaction of tyrosine to give dopa (dihydroxyphenylalanine), by virtue of its hydroxylase activity, and the conversion reaction of dopa to give dopaquinone, by virtue of its oxidase activity. This tyrosinase acts only when it is in mature form under the effect of certain biological factors.

A substance is acknowledged as being depigmenting if it acts directly on the vitality of the epidermal melanocytes where melanogenesis takes place, and/or if it interferes with one of the steps of melanin biosynthesis, either by inhibiting one of the enzymes involved in melanogenesis, or by inserting itself as a structural analogue of one of the chemical compounds of the melanin synthesis chain, which chain can then be blocked, thus ensuring depigmentation.

Arbutin and kojic acid are known as skin depigmenting agents. Certain ascorbic acid-based compounds are already known in the prior art for their depigmenting activity. In this regard, mention may be made in particular of EP1871334 and US20100204464.

Nevertheless, there remains the need for novel compounds which are effective agents for bleaching human skin, but which do not have their drawbacks of compounds already known from the art, while at the same time being stable in a composition, or else alternatively which have a reinforced action so that they are able to be used in a lower amount, thereby considerably reducing the potential side-effects observed.

In this regard, the Applicant has discovered, surprisingly and unexpectedly, that certain ascorbic 3-xyloside derivatives have good depigmenting activity, even at low concentration, without showing any cytotoxicity.

Moreover, women and men currently have a tendency to wish to appear youthful for as long as possible and consequently seek to tone down the signs of ageing of keratin materials such as skin ageing, which are reflected in particular by wrinkles and fine lines. In this regard, the advertising and fashion industries mention products for retaining radiant and wrinkle-free skin, signs of youthful skin, for as long as possible, all the more so since physical appearance has an effect on the psyche and/or on morale.

Hitherto, wrinkles and fine lines were treated using cosmetic products containing active agents acting on the skin, for example by improving its cell renewal or alternatively by promoting the synthesis, or preventing the degradation, of the elastic fibres which make up skin tissue.

It is known that human skin is constituted of two tissues; a surface tissue, the epidermis, and a deep tissue, the dermis.

Natural human epidermis is composed mainly of three types of cells, namely keratinocytes, which form the vast majority, melanocytes and Langerhans cells. The dermis provides the epidermis with a solid support. It is also its nourishing element. It is constituted mainly of fibroblasts and an extracellular matrix composed predominantly of collagen, elastin and a substance known as ground substance. These components are synthesized by the fibroblasts. Leukocytes, mast cells or else tissue macrophages are also found therein. Finally, blood vessels and nerve fibres pass through the dermis.

The dermal extracellular matrix is composed of proteins belonging to several large families: collagens, matrix glycoproteins other than collagens (fibronectin, laminin), elastin and proteoglycans. Glycosaminoglycans in free form (i.e. not bound to a protein) are also found in the extracellular matrix of the dermis. It is now well established that specific interactions exist between these various classes of proteins so as to give rise to a functional tissue.

An extracellular space (micromatrix) also exists in the epidermis. This space plays an extremely important functional role in cell tissue renewal and/or maintenance.

Proteoglycans are complex macromolecules formed from a branched central protein core, or network of proteins, to which very large numbers of polysaccharide side chains, called glycosaminoglycans, are attached.

In the remainder of the present application, proteoglycans will be denoted by the abbreviation PGs and glycosaminoglycans by the abbreviation GAGs.

GAGs have long been referred to by the expression "acid mucopolysaccharides" due to their high water retention capacity, their glucidic nature and their acid character originating from their multiple negative charges.

Thus, the polarity of GAGs makes them implicitly participate in certain biological functions such as tissue hydration, cation binding or an ionic filtration barrier role.

PGs and GAGs are synthesized by various cells in the dermis and epidermis: fibroblasts, keratinocytes and melanocytes.

Fibroblasts predominantly synthesize collagens, matrix glycoproteins other than collagens (fibronectin, laminin), GAGs, proteoglycans and elastin. Keratinocytes predominantly synthesize sulfate-containing GAGs and hyaluronic acid whereas melanocytes produce ostensibly no hyaluronic acid.

At the time of their incorporation into a PG, GAGs are in the form of linear chains composed of repeats of a base disaccharide always containing a hexosamine (glucosamine or galactosamine) and another monosaccharide (glucuronic acid, iduronic acid or galactose). The glucosamine is either N-sulfated or N-acetylated. On the other hand, the galactosamine is always N-acetylated. In addition, there may be sulfate groups O-linked to the hexosamine, uronic acid and galactose. The strong anionic nature of GAGs is explained by the presence of carboxylate groups within the hexuronic acids (glucuronic acid and iduronic acid) and of O- and N-linked sulfate groups.

The main GAGs are hyaluronic acid or hyaluronan (HA), heparan sulfate (HS), heparin (HP), chondroitin, chondroitin sulfate (CS), chondroitin 4-sulfate or chondroitin sulfate A (CSA), chondroitin 6-sulfate or chondroitin sulfate C (CSC), dermatan sulfate or chondroitin sulfate B (CSB) and keratan sulfate (KS), which differs from the other glycosaminoglycans by the presence of galactose in place of uronic acid. GAGs may also exist in the extracellular matrix in free form, that is to say not bound to a matrix protein: this is especially the case for hyaluronic acid. When PGs are synthesized, the GAGs are polymerized from these anchoring structures.

The synthesis of GAGs requires the coordinated and concerted action of very specific enzymes (transferases, epimerases, sulfotransferases) which are adjacent in the membrane of the endoplasmic reticulum and of the Golgi apparatus. A multitude of biochemical reactions (N-deacetylation, N- and O- sulfations, epimerization) then modify the two constituent monosaccharides of the base unit in a nonuniform manner along the chain. From one heparan sulfate chain to another, for example, the glucuronic acid/iduronic acid ratio, the nature, the number and the position of the O-sulfations, and also the N-sulfate/O-sulfate ratio can vary, which potentially offers an immense structural diversity.

Generally, the biological roles of PGs are highly diversified, ranging from a passive mechanical support function (for example serglycins) or from an ion barrier role in molecular filtration (for example perlecan and bamacan of the glomerular basement membrane) to more specific effects in cell adhesion, cell spreading, cell proliferation, cell differentiation or morphogenesis, or to very specific effects of PG-protein interactions, such as betaglycan receptor function or the interaction of decorin with collagen. They also play a fundamental role in the controlled release of various growth factors.

One of the roles of dermal connective tissue is to protect the body against external attacks while simultaneously forming an informative interface.

To do this, the dermis has high mechanical strength while maintaining, however, great flexibility.

Its strength is provided by the dense network of collagen fibres, but it is the PGs and the hyaluronic acid which, by providing the moisturization, distribution and flexibility of the fibres, make the difference between the skin and, for example, leather.

PGs make up 0.5% to 2% of the dry weight of the dermis; collagen, by itself, representing up to 80% thereof.

The concentration and distribution of GAGs and PGs in human skin vary with age.

Hyaluronic acid or hyaluronan (HA) is the main GAG of the dermis, the latter containing half the HA of the body. The synthesis of HA is performed in particular by the fibroblasts, close to the inner face of the plasma membrane. It is performed continuously. This gigantic polysaccharide (several million daltons) has a very high intrinsic viscosity, ensuring the moisturization and assembly of the various components of the connective tissue by forming supramolecular complexes.

Dermatan sulfate (DS), which was first isolated from the dermis, is also very abundant in the skin. It constitutes 40% to 50% of the dermal GAGs.

At the same time as the mechanisms contributing to the production of these specialized extracellular matrices, continual remodelling processes exist, the regulation of which depends on the balance between synthesis and degradation of the protein elements of the matrix.

Several families of matrix proteases are now described, and also the factors involved in the activation-inactivation thereof.

During chronological and/or photoinduced ageing, the dermis and the epidermis undergo numerous modifications and degradations which are reflected, with age, by flaccidness and a loss of suppleness of the skin.

Among the components degraded (in particular collagen and elastin), the PGs and GAGs are also adversely affected. Specifically, over the course of ageing, the fibroblasts and keratinocytes produce fewer and fewer PGs and GAGs and the synthesis thereof is imperfect. This results in significant disorganization: the deposition of GAGs on the protein backbone forming the PG is abnormal, which results in a lower affinity of these PGs for water and therefore a reduction in the hydration and tonicity of the tissues.

Restoring a normal production of PGs and GAGs by fibroblasts and keratinocytes contributes partially towards compensating for the loss of moisturization of the skin.

The degradation of these matrices thus contributes to the phenomenon of dryness and loss of suppleness of the skin.

The importance of having available products of which the effects are directed towards maintaining the level of PGs and GAGs in the skin and thus of maintaining, inter alia, good moisturization and good suppleness of the skin, can thus be appreciated.

The applicant has in particular also discovered, surprisingly and unexpectedly, that the novel ascorbic 3-xyloside derivative compounds are capable of improving the synthesis of sulfated glycosaminoglycans such as chondroitin sulfate and dermatan sulfate. These novel compounds are effective for improving epidermal renewal and firmness of the skin and for more effectively combatting the signs of ageing of the skin. They also have a beneficial effect on the structure of the dermal-epidermal junction, in particular on the cohesion between dermis and epidermis.

These novel compounds therefore find a particular application in compositions, in particular cosmetic compositions, intended for preventing and/or cosmetically treating ageing of the skin; especially preventing and/or treating, in particular topically, the signs of skin ageing, and most particularly the signs on the skin related to wrinkled skin, skin exhibiting impairment of its viscoelastic or biomechanical properties, skin exhibiting impairment in the cohesion of its tissues, thinned skin and/or skin exhibiting impairment of its surface appearance.

The present invention thus also relates to the non-therapeutic cosmetic use of compounds of formula (I) as defined hereinafter, for preventing, reducing and/or treating the signs of the ageing of keratin materials, in particular the signs of skin ageing.

The compositions according to the invention can make it possible more particularly to maintain and/or restore the mechanical properties of keratin materials impaired by the ageing process, such as the extensibility, tonicity, firmness, suppleness, density and/or elasticity properties of the skin.

The term“biomechanical or mechanical properties” is intended to mean herein more particularly the extensibility, tonicity, firmness, suppleness and/or elasticity properties of keratin materials, in particular of the skin.

The term "signs of skin ageing" is intended to mean herein any modification of the outer appearance of the skin due to ageing, whether it is chronobiological and/or extrinsic ageing, in particular photoinduced or hormonal ageing; among these signs, it is possible to distinguish:

- wrinkled skin, which is reflected in particular by the appearance of wrinkles and/or fine lines;

- skin exhibiting impairment of its viscoelastic or biomechanical properties, or skin exhibiting a lack of elasticity and/or of extensibility and/or of firmness and/or of suppleness and/or of tonicity, which is reflected in particular by wizened, flaccid, slack or saggy skin;

- skin exhibiting impairment of the cohesion of its tissues;

- thinned skin,

- skin exhibiting impairment of its surface appearance, which is reflected in particular by impairment of the grain of the skin, for example roughness. A subject of the invention is thus the compounds of formula (I) as defined below.

Likewise, a subject of the invention is a composition, preferably a cosmetic composition, comprising, in a physiologically acceptable medium, at least one compound of formula (I) as defined below.

Likewise, a subject of the invention is the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below.

The invention relates particularly to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below, as an agent for bleaching, lightening and/or depigmenting keratin materials, in particular the skin.

Likewise, the invention relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below, for combatting the signs of the ageing of keratin materials, in particular signs of skin ageing.

A subject of the invention is also a process for non-therapeutic cosmetic treatment of keratin materials, such as the skin, comprising the application to keratin materials, such as the skin, of at least one compound of formula (I) as defined below or of a composition, preferably a cosmetic composition, as defined below.

A subject of the invention is also particularly a non-therapeutic cosmetic treatment process for depigmenting, lightening and/or bleaching keratin materials, in particular the skin, comprising the application to the keratin materials, and in particular the skin, of at least one compound of formula (I) as defined below or of a composition containing same.

The compounds of formula (I) in accordance with the invention, as defined below, make it possible, cosmetically, to depigment and/or lighten efficiently, or even bleach, human keratin materials and in particular human skin. They are especially intended to be applied to the skin of individuals bearing brownish pigmentation blemishes or liver spots, or to the skin of individuals wishing to reduce the appearance of a brownish colour caused by melanogenesis.

The compounds of formula (I) in accordance with the invention can thus make it possible to depigment and/or lighten human keratin materials, and in particular the skin. More particularly, the keratin materials denote human skin and the compounds of formula (I) in accordance with the invention can thus make it possible to depigment and/or lighten human skin. The invention also relates to the use of a cosmetic composition as previously defined comprising at least one compound of formula (I) as previously described, for preventing and/or cosmetically treating the signs of the ageing of keratin materials, and in particular the signs on the skin. The invention also relates to the use of at least one compound of formula (I) as defined below or of a cosmetic composition as defined below, comprising at least one compound of formula (I), for preventing and/or cosmetically treating the signs of skin ageing, in particular the signs of skin ageing, in particular the signs on the skin chosen from wrinkled skin, skin exhibiting a detrimental modification of its viscoelastic or biomechanical properties, skin exhibiting a detrimental modification in the cohesion of its tissues, thinned skin, and skin exhibiting a detrimental modification of its surface appearance.

The invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below or of a cosmetic composition as defined below, comprising at least one compound of formula (I), for improving the firmness of the skin and/or for improving the structure of the dermal-epidermal junction and/or for reinforcing the cohesion between the dermis and the epidermis.

The invention also relates to a process for cosmetic treatment of the skin, comprising the application to the skin of at least one compound of formula (I) as defined above, or of a cosmetic composition as defined above. This process has an advantageous application in the treatment of the skin, especially of mature skin and/or wrinkled skin, in particular of the face and/or of the neck and/or of the hands and more particularly of the face and/or of the neck.

For the purposes of the present invention, the term“keratin materials” is intended to mean human keratin materials, and in particular human skin, lips and nails. The term "skin" is intended to mean all of the skin of the body, the mucous membranes and the semi-mucous membranes. More particularly, in the present invention, the skin of the neckline, the neck, the face and the hands, and in particular the skin of the face, are considered.

More particularly, for the purposes of the present invention, the keratin materials denote human skin. A subject of the invention is thus the novel compounds of formula (I) corresponding to formula (I) below:

and also the salts thereof, the solvates thereof and the optical isomers thereof, the geometric isomers thereof, the tautomers thereof, and/or the racemic mixtures thereof, alone or as a mixture.

The invention thus extends to the optical isomers, geometric isomers and/or tautomers of the compounds of formula (I), alone or as a mixture in any proportions, and also to the physiologically acceptable salts and/or the solvates of these compounds.

The ascorbic 3-xyloside derivatives in accordance with the invention can be used alone or as a mixture and in any proportion.

The anomeric C bond in formula (I) may be a or b.

For the purposes of the present invention, the term“mixture” relates to the mixtures of the various isomeric and/or tautomeric forms of one and the same compound, and likewise the mixtures of various compounds of general formula (I) and/or the respective isomeric or tautomeric forms thereof.

According to the present invention, the optical and/or geometric isomers of the compounds of formula (I) are chosen from the enantiomers, the diastereoisomers, the a or b anomers, and mixtures thereof.

According to a first variant of the invention, the compounds of formula (I) are a anomers. According to a second preferred variant of the invention, the compounds of formula (I) are b anomers.

In the context of the present invention, the salts of the compounds of formula (I) comprise the conventional non-toxic salts of said compounds such as those formed from a base. As salts of the compound of formula (I), mention may be made of the salts obtained by addition of the compound of formula (I) with a base, which may be organic or mineral.

The base may thus be a mineral base, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, lithium hydroxide, or sodium, potassium or calcium carbonate or hydrogen carbonate, for example. The base may also be an organic base such as a primary, secondary or tertiary alkylamine, for example triethylamine or butylamine. This primary, secondary or tertiary alkylamine may comprise one or more nitrogen and/or oxygen atoms and may thus comprise, for example, one or more alcohol functions; mention may be made especially of 2-amino-2- methylpropanol, ethanolamine, triethanolamine, 2-dimethylaminopropanol, 2- amino-2-(hydroxymethyl)-1 ,3-propanediol and 3-(dimethylamino)propylamine. The salts may also denote salts of addition with basic amino acids, for instance lysine, arginine or guanidine.

Advantageously, the salts of the compounds of formula (I) may be chosen from alkali metal or alkaline-earth metal salts such as sodium, potassium, calcium or magnesium salts; ammonium salts.

The solvates comprise conventional solvates such as those formed during the preparation of said compounds due to the presence of solvents. Examples that may be mentioned include solvates due to the presence of water or of linear or branched alcohols, such as ethanol or isopropanol.

Preferentially, the compounds of formula (I) denote in particular compounds 1 to 4 described below, and also the salts thereof, the solvates thereof and the optical isomers thereof, the geometric isomers thereof, and/or the racemic mixtures thereof, alone or as a mixture.

Table 1

Preferably, the compounds of formula (I) of the invention denote Compound 1 mentioned in Table 1 below, and also the salts thereof and the solvates thereof, alone or as a mixture:

and also the salts thereof, the solvates thereof and the optical isomers thereof, the geometric isomers thereof, and/or the racemic mixtures thereof, alone or as a mixture.

The compounds of the invention may be prepared according to scheme 1 below involving methods that are known and described for those skilled in the art. The tetronic derivative and also the xylose are orthogonally protected by methods known to those skilled in the art, described in the manual“Protecting Groups in Organic Synthesis” Greene, Wuts, Wiley Interscience. Once protected, the compounds are subjected to a chemical glycosylation reaction known to those skilled in the art, such as those described in particular in the manual“Handbook of Chemical Glycosylation” A. V. Demchenko Wiley VCH.

Scheme 1

in which scheme Z1 , Z2, Z3, Z5 are hydroxyl-protecting groups such as benzyl groups, it being possible for Z1 and Z2 to constitute, together with the oxygen atoms which bear them, a protective group of dimethylacetonide type,

Z4 denoting a functional group which makes it possible to provide orthogonal protection, but especially a reactivity specific for the anomeric position of the xylose derivative, such as a trifluoroacetimidate or trichloroacetimidate derivative or, in the preferred case of the invention, an alkynyl benzoate derivative of xylose.

The compounds of formula (I) according to the invention have a most particular application in the cosmetics field.

A subject of the invention is also a composition, preferably a cosmetic composition, containing at least one compound of formula (I), and also the salts thereof, the solvates thereof and the optical isomers thereof, the geometric isomers thereof, the tautomers thereof, and/or the racemic mixtures thereof, alone or as a mixture, in particular a composition containing at least one compound chosen from Compound 1 previously described, and also the salts thereof and/or the solvates thereof, alone or as a mixture.

The composition according to the invention is advantageously a cosmetic composition. The composition according to the invention is advantageously a composition intended for topical application.

The composition according to the invention advantageously comprises, in a physiologically acceptable medium, at least one compound of formula (I) as previously described, and also the salts thereof, the solvates thereof and the optical isomers thereof, the geometric isomers thereof, the tautomers thereof, and/or the racemic mixtures thereof, alone or as a mixture, in particular at least one compound chosen from Compound 1 previously described, and also the salts thereof and/or the solvates thereof, alone or as a mixture.

The term "physiologically acceptable medium" is intended to mean a medium that is compatible with human keratin materials such as the skin of the body or of the face, the lips, the mucous membranes, the eyelashes or the nails.

The compound(s) of formula (I) may be present in the composition according to the invention in an amount that may be between 0.01 % and 10% by weight, preferably between 0.1 % and 5% by weight, especially from 0.5% to 3% by weight, relative to the total weight of the composition.

The composition according to the invention is advantageously a cosmetic composition: it may comprise water and also adjuvants normally used in the cosmetics field.

Mention may be made in particular of organic solvents, especially C2- C6 alcohols; oils, especially hydrocarbon-based oils and silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic active agents, polymers, thickeners, preservatives, fragrances, bactericides, odour absorbers. These optional cosmetic adjuvants may be present in the composition in a proportion of from 0.001 % to 80% by weight and especially from 0.1 % to 40% by weight, relative to the total weight of the composition. In any case, these adjuvants, and the proportions thereof, will be chosen by those skilled in the art such that the advantageous properties of the compounds according to the invention are not, or are not substantially, adversely affected by the envisaged addition.

As active agents, it will be advantageous to introduce into the composition according to the invention at least one compound chosen from: desquamating agents; calmatives, organic or mineral photoprotective agents, moisturizers; depigmenting agents other than the compounds of formula (I) of the invention; anti-glycation agents; NO-synthase inhibitors; agents for stimulating the synthesis of dermal or epidermal macromolecules and/or for preventing their degradation; agents for stimulating fibroblast and/or keratinocyte proliferation or for stimulating keratinocyte differentiation; dermo-decontracting agents; tensioning agents; anti-pollution agents and/or free-radical scavengers; agents acting on the microcirculation; agents acting on the energy metabolism of cells; and mixtures thereof.

The composition according to the invention may be in any presentation form normally used in the cosmetics field, and especially in the form of an aqueous or aqueous-alcoholic solution, which is optionally gelled, a dispersion of the lotion type, which is optionally a two-phase lotion, an oil-in-water or water-in- oil or multiple (for example W/O/W or O/W/O) emulsion, an aqueous gel, a dispersion of oil in an aqueous phase by means of spherules, these spherules possibly being polymer nanoparticles such as nanospheres and nanocapsules or, better still, lipid vesicles of the ionic and/or non-ionic type; aqueous or oily gels. These compositions are prepared according to the usual methods. The composition according to the invention may constitute a skincare composition, and especially a cleansing, protecting, treating or care cream for the face, the hands, the feet, the major anatomical folds or the body (for example day creams, night creams, makeup-removing creams, foundation creams or antisun creams); a fluid foundation, a makeup-removing milk, a protective or care body milk or an antisun milk; a skincare lotion, gel or foam, such as a cleansing lotion.

A subject of the invention is also a non-therapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, in particular the skin, comprising the application of the composition previously described.

According to one advantageous variant of the invention, it is a non- therapeutic cosmetic process for depigmenting, lightening and/or bleaching the skin. The invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as previously defined, and also the salts thereof, the solvates thereof and the optical isomers thereof, the geometric isomers thereof, the tautomers thereof, and/or the racemic mixtures thereof, alone or as a mixture, and more particularly of at least one compound chosen from Compound 1 previously described, and also the salts thereof and/or the solvates thereof, alone or as a mixture, as an agent for bleaching, lightening and/or depigmenting keratin materials, in particular the skin. In these schemes, "a.t" signifies ambient temperature.

The invention is illustrated in greater detail by the following non-limiting examples. Example 1 : Synthesis of Compound No. 1

Compound 1 E

Procedure:

The vitamin or L-ascorbic acid is converted, according to the methods described in the following articles, into compound A. One-pot 2-O-alkylation of L-ascorbic acid, Thopate, Shankar R.; Dengale, Rohit A.; Kulkarni, Mukund G.; Synlett (2013), 24(12), 1555-1557. Rational Approach to Selective and Direct 2-O- Alkylation of 5,6-O-lsopropylidene-L-ascorbic Acid; Olabisi, Ayodele O.; Wimalasena, Kandatege; Journal of Organic Chemistry (2004), 69(21 ), 7026- 7032.

The xylose is converted, according to the methods described below, into compound B.

2-(1 -hexyn-1 -yl)benzoic acid; Yu, Biao; Cao, Xin; e-EROS Encyclopedia of Reagents for Organic Synthesis (2014), 1 -4. Publisher: (John Wiley & Sons, Ltd., Chichester, UK). Total Synthesis of Linckosides A and B, the Representative Starfish Polyhydroxysteroid Glycosides with Neuritogenic Activities; Dapeng Zhu and Biao Yu; J. Am. Chem. Soc., 2015, 137 (48), pp 15098-15101 .

The glycosylation reaction is then mediated by a gold complex as described in J. Am. Chem. Soc., 2015, 137 (48), pp 15098-15101 above. The final deprotection is carried out according to the conditions known to those skilled in the art, by performing an acid hydrolysis, followed by a hydrogenolysis, then a saponification so as to result in Compound 1 .

The MS and NMR spectra are in accordance with the desired product.

Example 2: Demonstration of the depigmenting activity

The measurement of the depigmenting activity (reduction of melanin production) of compounds of formula (I) was performed by assaying normal human melanocytes in vitro as follows.

First of all, normal human melanocytes are cultured and dispensed into wells. After 24 hours, the culture medium was replaced with a medium containing compounds of formula (I) to be evaluated. The cells were incubated 72 hours before measurement of the final optical density, which measures the amount of melanin produced by the melanocytes. A dose effect was performed using a wide concentration range of the compounds evaluated. Thus, by making the concentrations and the melanin measurements correspond, it was possible to determine an IC50 in mM: concentration at which a 50% decrease in melanin synthesis is achieved.

Various test campaigns were conducted and the results are collated in the tables below.

Table 2

NA: not active

Surprisingly, the compounds of formula (I) showed a strong depigmenting effect.

Coculture experiment:

A biological test demonstrated the depigmenting activity of Compound 1.

The modulatory effect on melanogenesis of Compound 1 was measured according to the method described in the patent FR-A-2734825, and also in the article by R. Schmidt, P. Krien and M. Regnier, Anal. Biochem., 235(2), 113- 18,1996. This test is performed on a coculture of keratinocytes and melanocytes.

For the compounds tested, the following were determined:

- the cytotoxicity,

- the inhibitory activity on melanin synthesis, by estimating the melanin optical density.

The IC50 values (concentration for which 50% of the melanin synthesis is inhibited) were determined.

Compound 1 : non-cytotoxic, IC50 = 15 mM.

Ascorbic acid: non-cytotoxic, IC50 not determined, not active.

Example 3: Demonstration of the anti-ageing activity

The effects of the compounds on the neosynthesis of total and sulfated glycosaminoglycans (GAGs) were studied on a cell model, normal human dermal fibroblasts (NHDFs). The effects of these compounds were evaluated by measuring:

the incorporation of [3H]-sulfate into the total GAGs neosynthesized by NHDFs, the incorporation of [35S]-sulfate into the sulfated GAGs neosynthesized by NHDFs.

The NHDF fibroblasts were seeded into a 96-well plate and cultured in culture medium for 24 hours. The medium was then replaced with culture medium containing or not containing (control) the compounds to be tested or the reference (TGF-b at 10 ng/ml), then the cells were incubated for 72 hours with the addition of the [3FI]-glucosamine radioactive label (total GAGs) or of the [35S]-sulfate radioactive label (sulfated GAGs) for the final 24 hours of incubation.

At the end of the incubation, the glycosaminoglycans were extracted from the cells with a chaotropic buffer. The GAGs were then purified by ion exchange chromatography: adsorption of the anionic molecules on Q-Sepharose beads and desorption of the molecules of low or medium anionic nature, with a suitable solution.

All the experimental conditions were performed in n=3.

The radioactivity incorporated into the molecules left on the support (GAGs, predominantly) was measured by liquid scintillation.

The inter-group comparisons were performed using the Student's non-paired two- sided T-test. The statistical analyses can be interpreted in n>5; however, for n<5, the data calculated are provided only by way of indication.

Standard error of the mean:

sem = standard deviation (Sd)/ Vn

The standard error of the mean (sem) represents the deviation of the sample mean relative to the true population mean. The sem is calculated by dividing the Sd by the square root of the sample size.

Cpm: counts per minute

Sd: standard deviation

Effect on the synthesis of sulfated glycosaminoglycans by NFIDFs

Effect on the synthesis of total glycosaminoglycans by NHDFs

^*: 0.01 to 0.05, Significant

Surprisingly, Compound 1 , tested at 100 mM, weakly but significantly stimulated the neosynthesis of total and sulfated GAGs by NHDFs (respectively 115% and 126% of the control).

Example 4: Cosmetic composition

A cosmetic skin depigmenting composition is prepared, comprising (in grams):

Compound No. 1 2 g

PEG400 68 g

Ethanol 30 g

The cosmetic composition applied daily to the skin makes it possible to lighten the skin of the face.

Example 5: cosmetic gel

A skin depigmenting gel is prepared, comprising (% by weight):

Compound No. 1 0.25%

Carbomer (Carbopol 981 from Lubrizol) 1 %

preservative qs

water qs 100%

Claims

1. Compounds of formula (I):

2. Compounds according to the preceding claim, in which:

and also the salts thereof, the solvates thereof, the enantiomers thereof, the diastereoisomers thereof, the a or b anomers thereof, and/or the racemic mixtures thereof, alone or as a mixture.

3. Compounds according to either of the preceding claims, chosen from:

4. Compounds according to one of the preceding claims, chosen from:

5. Composition, preferably cosmetic composition, comprising, in a physiologically acceptable medium, at least one compound of formula (I) according to any one of the preceding claims.

6. Composition according to the preceding claim, characterized in that compound (I) is present in a content of between 0.01 % and 10% by weight, preferably between 0.01 % and 10% by weight, preferably between 0.1 % and 5% by weight and preferentially from 0.5% to 3% by weight, relative to the total weight of the composition.

7. Composition according to either of Claims 5 and 6, characterized in that it comprises at least one adjuvant chosen from the group formed by organic solvents, especially C2-C6 alcohols; oils, especially hydrocarbon-based oils and silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic active agents, organic or mineral photoprotective agents, polymers, thickeners, preservatives, fragrances, bactericides, ceramides, odour absorbers, antioxidants.

8. Composition according to any one of Claims 5 to 7, characterized in that it comprises at least one active agent chosen from desquamating agents; calmatives, organic or mineral photoprotective agents, moisturizers; depigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents for stimulating the synthesis of dermal or epidermal macromolecules and/or for preventing their degradation; agents for stimulating fibroblast and/or keratinocyte proliferation or for stimulating keratinocyte differentiation; tensioning agents; anti- pollution agents and/or free-radical scavengers; agents acting on the microcirculation; agents acting on the energy metabolism of cells; and mixtures thereof.

9. Process for non-therapeutic cosmetic treatment of keratin materials, such as the skin, comprising the application to said keratin materials, such as the skin, of at least one compound of formula (I) as defined in one of Claims 1 to 4 or of a composition, preferably a cosmetic composition, as defined in one of Claims 5 to 8.

10. Non-therapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, such as the skin, comprising the application of at least one compound of formula (I) as defined according to any one of Claims 1 to 4, or of a composition containing same according to any one of Claims 5 to 8, to said keratin materials.

11. Process according to the preceding claim, for depigmenting, lightening and/or bleaching the skin.

12. Process according to Claim 9, in which the composition is applied to mature and/or wrinkled skin.

13. Non-therapeutic cosmetic use of at least one compound of formula (I) as defined according to any one of Claims 1 to 4.

14. Non-therapeutic cosmetic use according to Claim 12 of at least one compound of formula (I) as defined according to any one of Claims 1 to 4, as an agent for bleaching, lightening and/or depigmenting keratin materials.

15. Non-therapeutic cosmetic use according to Claim 12 of at least one compound of formula (I) as defined according to any one of Claims 1 to 4, for preventing and/or treating the signs of the ageing of keratin materials, such as the signs of skin ageing.

16. Non-therapeutic cosmetic use according to Claim 15 of at least one compound of formula (I) as defined in one of Claims 1 to 4, or of a composition, preferably a cosmetic composition, as defined in one of Claims 5 to 8, for improving the firmness of the skin.