WO2009034559A2 - Cosmetic process for aesthetic and/or repairing treatment of the skin - Google Patents

Abstract

The present invention relates to a cosmetic process for aesthetic and/or repairing treatment of the skin of an individual, comprising at least one step of administering, to the said individual, according to a mesotherapy technique, a sterile fluid composition containing, in a physiologically acceptable medium, at least one C-glycoside derivative.

Description

The present invention relates to the field of cosmetics and in particular concerns a novel cosmetic process for aesthetic and/or repairing treatment of the skin.

In particular, the invention relates to a process comprising the use of compounds of the C-glycoside family or of a composition containing them, for preventing, reducing or treating unaesthetic aspects of the skin associated with ageing and/or photo- ageing.

For the purposes of the invention, the term "ageing of the skin" means ageing of chronobio logical origin, also comprising ageing associated with the lifestyle, such as ageing of the skin associated with the consumption of tobacco or alcohol, and "photo- ageing of the skin" means ageing of the skin essentially following exposure to solar radiation.

Human skin is constituted of two compartments, namely an upper compartment, the epidermis, and a deep compartment, the dermis.

The cohesion between the epidermis and the dermis is ensured by the dermo- epidermal junction. This is a complex region about 100 nm thick, which comprises the basal pole of the basal keratinocytes, the epidermal membrane and the sub-basal zone of the upper dermis (Bernard P., Structure de Ia jonction dermo-epidermique. Objectif peau.

2001, 68: 87-93).

The dermis provides the epidermis with a solid support. It is also its nourishing factor. It is mainly constituted of fibroblasts and of an extracellular matrix. Leukocytes, mastocytes and tissue macrophages are also present therein. It is also constituted of blood vessels and nerve fibres.

The extracellular matrix of the dermis, like that of all the connective tissues of the body, is composed of proteins belonging to several major families: collagens, matrix glycoproteins other than collagens (fibronectin, laminin), elastin and proteoglycans, and also glycosaminoglycans in free form (i.e. not bound to a protein).

It is now well established that specific interactions exist between these various classes of protein to give rise to a functional tissue.

Proteoglycans (PG) are complex macro molecules constituted of a branched central protein trunk, or protein network, to which are attached numerous polysaccharide side chains known as glycosaminoglycans (GAG).

GAGs were for a long time referred to as acidic mucopolysaccharides on account of their high water-retaining capacity, their carbohydrate nature and their acidic nature originating from their multiple negative charges. Thus, the polarity of GAGs makes them implicitly participate in certain biological functions such as the hydration of tissues, the binding of cations or the barrier role of ionic filtration. Ageing of the skin is an inevitable phenomenon, which progresses slowly and is irreversible, leading to anatomical and histological changes. The first visible signs appear on the skin as impairments in the texture, colour and transparency and by the appearance of wrinkles.

According to professionals working in the field of aesthetics, there are three types of change associated with the ageing of facial skin: atrophy, slackening and fattening.

Atrophy corresponds to the massive reduction of the thickness of skin tissue, affecting both the dermal connective tissue and the number of cellular layers of the epidermis. Slackening of the subcutaneous tissues (fats and muscles) leads to an excess of skin and ptosis. This slackening is characterized by drooping of the cheekbones and of the cheeks, entraining the lower eyelid.

As regards fattening, this corresponds to the increase in excess weight with age. On the face, it is reflected essentially by swelling of the bottom of the face and of the neck.

These three types of change are also generally associated with dryness and roughness of the skin, which are tangible impairments of the cutaneous coating, with which is associated loss of elasticity. The skin then forms folds and, under the effect of traction, it forms a long-lasting fold, which only slowly recovers its initial position. It is understood that these visual signs are themselves the consequence of structural and physiological changes that take place in the skin.

As regards the epidermis, ageing is manifested mainly by the reduction of its thickness. With age, the cellular divisions of the basal layer decrease, and the epidermis becomes thinner. As regards the dermis, an impairment of all these matrix molecules is observed in the course of ageing. A decrease in the solubility of the collagen molecules, impairment of their mechanical properties and a decrease in their hydrating power are noted in particular. The elastic fibres become scarcer, lose their orientation, and the absence of hydration impairs their elastic property and leads to breakage.

Thus, during ageing, the GAGs and PGs degrade and wrinkles appear at the surface of the skin.

Ageing of the skin is a genetically programmed mechanism; however, certain environmental factors such as smoking and above all exposure to solar radiation accelerate it. The skin thus has a much older appearance on the areas exposed to sunlight, such as the back of the hands or the face.

All these phenomena lead to an unaesthetic appearance of the skin, which many people seek to prevent or correct. It is known that such slackening may be corrected immediately by applying to the skin compounds capable of making the skin taut by a tensioning effect, this tension smoothing out the skin and immediately reducing the wrinkles and fine lines, or even making them disappear altogether.

However, the efficacy of such tensioning agents is limited over time, and tends to disappear in the course of a day. What is more, these tensioning agents are effective only on the surface wrinkles of the skin, and have less effect on the deeper wrinkles, for which their action is poor and very short-lived.

It is also possible to obtain a deeper action against wrinkles by using agents that act directly in the dermal and epidermal tissues to regenerate the biological molecules, especially the GAGs and PGs, which tend to undergo accelerated degradation or whose synthesis tends to decrease in the course of ageing.

Many compounds exist that are capable of stimulating the synthesis of the macro molecules present in the dermo-epidermal junction and in the dermis.

However, when applied topically, these molecules penetrate only sparingly, thus exerting only a limited effect over time and in intensity.

The aim of the present invention is, precisely, to propose a novel cosmetic process for aesthetic improvement of the skin, for preventing, reducing, eliminating or limiting the effect of ageing on the appearance of the skin, whether it is of chronobiological or photo-induced origin, and especially the effects generated by a decrease in the elasticity of the skin and/or by degradation of the GAGs and PGs in the structure of the tissues.

Thus, one object of the present invention is to provide a cosmetic process for aesthetic and/or repairing treatment of the skin in which the cutaneous bioavailability of C- glycoside derivative is substantially improved.

The present invention also proposes a cosmetic process for aesthetic and/or repairing treatment of the skin, for treating and/or preventing and/or reducing the signs of ageing or photo-induced ageing of the skin.

The present invention also proposes a cosmetic process for aesthetic and/or repairing treatment of the skin, for obtaining an improved facial rejuvenating and skin tensioning effect.

The present invention also proposes a cosmetic process for aesthetic and/or repairing treatment of the skin, for obtaining an improved anti-ageing effect.

Thus, according to a first aspect, a subject of the present invention is a cosmetic process for aesthetic and/or repairing treatment of the skin of an individual, comprising at least one step of administering, to the said individual, according to a mesotherapy technique, a fluid composition, which is preferably liquid and sterile, containing, in a physiologically acceptable medium, at least one C-glycoside derivative of general formula (I) as defined below.

For the purposes of the present invention, the term "skin" means the skin, the lips and mucous membranes.

Mesotherapy is a treatment technique by intra-epidermal and/or intradermal and/or subcutaneous injection of active product(s), for instance micronutrients, vitamins and/or hyaluronic acid. The compositions are administered according to this technique by injection in the form of small multiple droplets into the epidermis, the dermo-epidermal junction and/or the dermis in order especially to perform subcutaneous layering. The mesotherapy technique is especially described in the publication "Traite de mesotherapie" by Jacques Le Coz, published by Masson, 2004.

Mesotherapy performed on the face is also known as a mesolift or mesoglow.

The combination of C-glycoside derivatives and of the mesotherapy technique is reflected on the one hand by an increase in the bioavailability of these derivatives, thus making it possible to reinforce their cosmetic efficacy. In particular, the cosmetic efficiency is notably due to the improvement of the sulfated GAGs synthesis, such as the chondroitin sulfate and the dermatan sulfate, and more particularly the chondroitin sulfate. The cosmetic efficiency is also due to the improvement of the expression of proteoglycans heparan sulfate. This cosmetic efficiency allows to improve the renewal and the firmness of the skin and to more efficiently fight against the signs of cutaneous ageing.

The combination of C-glycosides and of the mesotherapy technique leads, on the other hand, to a phenomenon of neosynthesis of scar collagen under the mechanical effect of the injections themselves, thus reinforcing the effect of the C-glycoside derivatives.

These two phenomena combine to produce an improved, or even synergistic, cosmetic and especially aesthetic and/or repairing effect. For obvious reasons, this beneficial effect is particularly effective for treating the wrinkles and fine lines of the skin. The present invention may thus be advantageously used for treating, preventing and/or reducing the unaesthetic effects of ageing of the skin. For the purposes of the invention, the term "preventing" means reducing the risk of occurrence of a phenomenon.

The process in accordance with the present invention thus proves to be advantageous for treating ageing of the skin and/or photo-ageing of the skin. It also makes it possible to prevent and/or treat the signs of ageing or photo- ageing of the skin chosen from wrinkled skin, skin showing an impairment of its viscoelastic or biomechanical properties, skin showing an impairment in the cohesion of its tissues, thinned skin, dull skin lacking radiance, skin showing an impairment of its surface aspect and/or grain, and skin showing a decrease in cellular energy metabolism, in a device for intradermal and/or intra-epidermal and/or subcutaneous administration.

According to another of its aspects, the present invention is directed towards a device that is suitable for storing at least one C-glycoside and, where appropriate, for mixing it with a liquid physiologically acceptable medium, in a sterile environment, the said device comprising at least one sterile container and at least one C-glycoside placed in the said container, the said C-glycoside derivative being of general formula I as defined hereinbelow.

The device according to the invention is, of course, arranged to allow, moreover, the withdrawal of the said C-glycoside in solution or dispersion form.

Thus, according to a first embodiment, the said container is breakable to allow the withdrawal of the said C-glycoside.

For example, it may be in the form of a one-dose ampule or capsule, having a breakable end. According to a second embodiment, the said container has a cover allowing hermetic closure during storage, which cover may be pierced by a needle at the time of use.

According to one embodiment variant, the C-glycoside is formulated in the form of a dispersion or a solution in the container. According to another variant, the C-glycoside is present therein in powder form. In such a variant, the said container is suitable for introducing a fluid, sterile physiologically acceptable medium to obtain a solution and/or dispersion of the said C- glycoside under sterile conditions.

Such a container may also have two compartments, one of the compartments being intended for storing the C-glycoside in powder form and the other for that of the liquid physiologically acceptable medium that is to be combined therewith. These two compartments are advantageously separated by a stoppering means that is configured to be moved and thus allow mixing of the contents of the two compartments.

Such a device is advantageously intended for a single use. The term "sterile environment" means an environment which can ensure harmlessness for the compound(s) and/or the composition it contains, as required for intra- epidermal and/or intradermal and/or subcutaneous administration.

In particular, it is essential that the composition formed from the physiologically acceptable medium containing the C-glycoside, and that is to be administered according to a mesotherapy technique, be free of any contaminating body liable to initiate an undesirable side reaction in the host body. Thus, the administered composition should be free of viable or revivable, potentially infectious microorganisms known to those skilled in the art.

To satisfy this requirement, the liquid physiologically acceptable medium and the C-glycoside forming the administrable composition according to the invention have been subjected, together or separately, to a sterilization process according to one of the conventional methods well known to those skilled in the art, for instance heating in an autoclave, or ionizing irradiation, such as by ultraviolet rays, an electron beam or gamma rays.

C-GLYCOSIDE DERIVATIVES

In general, the C-glycoside derivative that is suitable for use in the invention corresponds to the general formula (I) below:

X-R

⁸^ (D in which:

- R represents a saturated C₁-C₁₀ and in particular a Ci -C₄ alkyl radical, which may be optionally substituted with at least one radical chosen from OH, COOH and

COOR"2 with R"2 being a saturated C1-C4 alkyl radical, in particular an ethyl radical,

- S represents a monosaccharide or a polysaccharide comprising up to 20 sugar units and in particular up to 6 sugar units, in pyranose and/or furanose form and of L and/or D series, the said mono- or polysaccharide possibly being substituted with a mandatorily free hydroxy 1 group, and optionally one or more optionally protected amine function(s), and

- X represents a radical chosen from the groups -CO-, -CH(OH)-, -CH(NH₂)-, -CH(NHCH₂CH₂CH₂OH)-, -CH(NHPh)- and -CH(CH₃)- and in particular a radical -CO-, -CH(OH)- or -CH(NH₂)- and more particularly a radical -CH(OH)-, - the bond S-CH₂-X represents a bond of C-anomeric nature, which may be CC or β, and also the cosmetically acceptable salts thereof, solvates thereof such as hydrates, and optical and geometrical isomers thereof.

Preferably, R denotes a Ci-C₆ , in particular Ci-C₄ and preferentially Ci-C₂ saturated linear alkyl radical and more preferentially a methyl radical.

Among the alkyl groups that are suitable for use in the invention, mention may be made especially of methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, isobutyl, sec- butyl, pentyl, n-hexyl, cyclopropyl, cyclopentyl and cyclohexyl groups.

According to one embodiment of the invention, a C-glycoside derivative may be used corresponding to formula (I) for which S may represent a monosaccharide or a polysaccharide containing up to 6 sugar units, in pyranose and/or furanose form and of L and/or D series, the said mono- or polysaccharide containing at least one mandatorily free hydro xyl function and/or optionally one or more mandatorily protected amine functions, X and R otherwise conserving all the definitions given previously. Advantageously, a monosaccharide of the invention may be chosen from D- glucose, D-galactose, D-mannose, D-xylose, D-lyxose, L-fucose, L-arabinose, L- rhamnose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D- glucosamine and N-acetyl-D-galactosamine, and advantageously denotes D-glucose, D- xylose, N-acetyl-D-glucosamine or L-fucose, and in particular D-xylose.

More particularly, a polysaccharide of the invention containing up to 6 sugar units may be chosen from D-maltose, D-lactose, D-cellobiose, D-maltotriose, a disaccharide combining an iduronic acid chosen from D-iduronic acid and D-glucuronic acid with a hexosamine chosen from D-galactosamine, D-glucosamine, N-acetyl-D- galactosamine, N-acetyl-D-glucosamine, an oligosaccharide containing at least one xylose that may be advantageously chosen from xylobiose, methyl-β-xylobioside, xylotriose, xylotetraose, xylopentaose and xylohexaose, and especially xylobiose, which is composed of two xylose molecules linked via a 1-4 bond.

More particularly, S may represent a monosaccharide chosen from D-glucose, D-xylose, L-fucose, D-galactose and D-maltose, and especially D-xylose.

Preferentially, a C-glycoside derivative of formula (I) is used for which: - R denotes an unsubstituted linear Ci -C₄ and especially Ci-C₂ alkyl radical, in particular methyl;

- S represents a monosaccharide as described previously, chosen in particular from D-glucose, D-xylose, N-acetyl-D-glucosamine and L-fucose, and in particular D- xylose; - X represents a group chosen from -CO-, -CH(OH)- and -CH(NH₂)- and preferentially a group -CH(OH)-.

The salts that are acceptable for the non-therapeutic use of the compounds described in the present invention comprise conventional non-toxic salts of the said compounds such as those formed from organic or mineral acids. By way of example, mention may be made of the salts of mineral acids, such as sulfuric acid, hydrochloric acid, hydrobromic acid, hydriodic acid, phosphoric acid or boric acid. Mention may also be made of the salts of organic acids, which may comprise one or more carboxylic, sulfonic or phosphonic acid groups. They may be linear, branched or cyclic aliphatic acids or alternatively aromatic acids. These acids may also comprise one or more heteroatoms chosen from O and N, for example in the form of hydroxyl groups. Mention may be made especially of propionic acid, acetic acid, terephthalic acid, citric acid and tartaric acid. When the compound of formula (I) comprises an acidic group, neutralization of the acid group(s) may be performed with a mineral base, such as LiOH, NaOH, KOH, Ca(OH)₂, NH₄OH, Mg(OH)₂ or Zn(OH)₂; or with 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, triethanolamine, 2-dimethylaminopropanol and 2-amino-2-(hydroxymethyl)-l,3-propanediol. Mention may also be made of lysine or 3- (dimethy lamino)propy lamine . The solvates that are acceptable for the compounds described in the present invention comprise conventional solvates such as those formed during the final step of preparation of the said compounds due to the presence of solvents. By way of example, mention may be made of the solvates due to the presence of water or of linear or branched alcohols such as ethanol or isopropanol. Among the C-glycoside derivatives of formula (I) used according to the invention, the following are most particularly considered:

1. C-β-D-xylopyranoside-n-propan-2-one;

2. C-α-D-xylopyranoside-n-propan-2-one;

3. 1 -[2-(3-hydroxypropylamino)propyl]-C-β-D-xylopyranose; 4. l-[2-(3-hydroxypropylamino)propyl]-C-α-D-xylopyranose;

5. C-β-D-xylopyranoside-2-hydroxypropane;

6. C-α-D-xylopyranoside-2-hydroxypropane;

7. C-β-D-xylopyranoside-2-aminopropane;

8. C-α-D-xylopyranoside-2-aminopropane; 9. C-β-D-xylopyranoside-2-phenylaminopropane;

10. C-α-D-xylopyranoside-2-phenylaminopropane;

11. ethyl 3-methyl-4-(C-β-D-xylopyranoside)butyrate;

12. ethyl 3-methyl-4-(C-α-D-xylopyranoside)butyrate;

13. 6-(C-β-D-xylopyranoside)-5-ketohexanoic acid; 14. 6-(C-α-D-xylopyranoside)-5-ketohexanoic acid;

15. 6-(C-β-D-xylopyranoside)-5-hydroxyhexanoic acid;

16. 6-(C-α-D-xylopyranoside)-5-hydroxyhexanoic acid; 17. 6-(C-β-D-xylopyranoside)-5-aminohexanoic acid;

18. 6-(C-α-D-xylopyranoside)-5-aminohexanoic acid;

19. 6-(C-β-D-xylopyranoside)-5-phenylaminohexanoic acid;

20. 6-(C-α-D-xylopyranoside)-5-phenylaminohexanoic acid; 21. l-(C-β-D-xylopyranoside)hexane-2,6-diol;

22. 1 -(C-α-D-xylopyranoside)hexane-2,6-diol;

23. 5-(C-β-D-xylopyranoside)-4-ketopentanoic acid;

24. 5-(C-α-D-xylopyranoside)-4-ketopentanoic acid;

25. 5-(C-β-D-xylopyranoside)-4-hydroxypentanoic acid; 26. 5-(C-α-D-xylopyranoside)-4-hydroxypentanoic acid;

27. 5-(C-β-D-xylopyranoside)-4-aminopentanoic acid;

28. 5-(C-α-D-xylopyranoside)-4-aminopentanoic acid;

29. 5-(C-β-D-xylopyranoside)-4-phenylaminopentanoic acid;

30. 5-(C-α-D-xylopyranoside)-4-phenylaminopentanoic acid; 31. 1 -(C-β-D-xylopyranoside)pentane-2,5-diol;

32. 1 -(C-α-D-xylopyranoside)pentane-2,5-diol;

33. 1 -(C-β-D-fucopyranoside)propan-2-one;

34. 1 -(C-α-D-fucopyranoside)propan-2-one;

35. 1 -(C-β-L-fucopyranoside)propan-2-one; 36. l-(C-α-L-fucopyranoside)propan-2-one;

37. 1 -(C-β-D-fucopyranoside)-2-hydroxypropane;

38. 1 -(C-α-D-fucopyranoside)-2-hydroxypropane;

39. 1 -(C-β-L-fucopyranoside)-2-hydroxypropane;

40. 1 -(C-α-L-fucopyranoside)-2-hydroxypropane; 41. l-(C-β-D-fucopyranoside)-2-aminopropane;

42. 1 -(C-α-D-fucopyranoside)-2-aminopropane;

43. 1 -(C-β-L-fucopyranoside)-2-aminopropane;

44. 1 -(C-α-L-fucopyranoside)-2-aminopropane;

45. 1 -(C-β-D-fucopyranoside)-2-phenylaminopropane; 46. l-(C-α-D-fucopyranoside)-2-phenylaminopropane; 47. 1 -(C-β-L-fucopyranoside)-2-phenylaminopropane;

48. 1 -(C-α-L-fucopyranoside)-2-phenylaminopropane;

49. ethyl 3-methyl-4-(C-β-D-fucopyranoside)butyrate;

50. ethyl 3-methyl-4-(C-α-D-fucopyranoside)butyrate; 51. ethyl 3-methyl-4-(C-β-L-fucopyranoside)butyrate;

52. ethyl 3-methyl-4-(C-α-L-fucopyranoside)butyrate;

53. 6-(C-β-D-fucopyranoside)-5-ketohexanoic acid;

54. 6-(C-α-D-fucopyranoside)-5-ketohexanoic acid;

55. 6-(C-β-L-fucopyranoside)-5-ketohexanoic acid; 56. 6-(C-α-L-fucopyranoside)-5-ketohexanoic acid;

57. 6-(C-β-D-fucopyranoside)-5-hydroxyhexanoic acid;

58. 6-(C-α-D-flιcopyranoside)-5-hydroxyhexanoic acid;

59. 6-(C-β-L-fucopyranoside)-5-hydroxyhexanoic acid;

60. 6-(C-α-L-fucopyranoside)-5-hydroxyhexanoic acid; 61. 6-(C-β-D-fucopyranoside)-5-aminohexanoic acid;

62. 6-(C-α-D-fucopyranoside)-5-aminohexanoic acid;

63. 6-(C-β-L-fucopyranoside)-5-aminohexanoic acid;

64. 6-(C-α-L-fucopyranoside)-5-aminohexanoic acid;

65. l-(C-β-D-fucopyranoside)hexane-2,6-diol; 66. l-(C-α-D-fucopyranoside)hexane-2,6-diol;

67. l-(C-β-L-fucopyranoside)hexane-2,6-diol;

68. l-(C-α-L-fucopyranoside)hexane-2,6-diol;

69. 5-(C-β-D-fucopyranoside)-4-ketopentanoic acid;

70. 5-(C-α-D-fucopyranoside)-4-ketopentanoic acid; 71. 5-(C-β-L-fucopyranoside)hexane-2,6-diol)-4-ketopentanoic acid;

72. 5-(C-α-L-fucopyranoside)hexane-2,6-diol)-4-ketopentanoic acid;

73. 5-(C-β-D-fucopyranoside)-4-hydroxypentanoic acid;

74. 5-(C-α-D-flιcopyranoside)-4-hydroxypentanoic acid;

75. 5-(C-β-L-fucopyranoside)-4-hydroxypentanoic acid; 76. 5-(C-α-L-fucopyranoside)-4-hydroxypentanoic acid; 77. 5-(C-β-D-fucopyranoside)-4-aminopentanoic acid;

78. 5-(C-α-D-fucopyranoside)-4-aminopentanoic acid;

79. 5-(C-β-L-fucopyranoside)-4-aminopentanoic acid;

80. 5-(C-α-L-fucopyranoside)-4-aminopentanoic acid; 81. l-(C-β-D-fucopyranoside)pentane-2,5-diol;

82. l-(C-α-D-fucopyranoside)pentane-2,5-diol;

83. l-(C-β-L-fucopyranoside)pentane-2,5-diol;

84. l-(C-α-L-fucopyranoside)pentane-2,5-diol;

85. 1 -(C-β-D-glucopyranosyl)-2-hydroxypropane; 86. l-(C-α-D-glucopyranosyl)-2-hydroxypropane;

87. 1 -(C-β-D-glucopyranosyl)-2-aminopropane;

88. l-(C-α-D-glucopyranosyl)-2-aminopropane;

89. 1 -(C-β-D-glucopyranosyl)-2-phenylaminopropane;

90. 1 -(C-α-D-glucopyranosyl)-2-phenylaminopropane; 91. ethyl 3-methyl-4-(C-β-D-glucopyranosyl)butyrate;

92. ethyl 3-methyl-4-(C-α-D-glucopyranosyl)butyrate;

93. 6-(C-β-D-glucopyranosyl)-5-ketohexanoic acid;

94. 6-(C-α-D-glucopyranosyl)-5-ketohexanoic acid;

95. 6-(C-β-D-glucopyranosyl)-5-hydroxyhexanoic acid; 96. 6-(C-α-D-glucopyranosyl)-5-hydroxyhexanoic acid;

97. 6-(C-β-D-glucopyranosyl)-5-aminohexanoic acid;

98. 6-(C-α-D-glucopyranosyl)-5-aminohexanoic acid;

99. 6-(C-β-D-glucopyranosyl)-5-phenylaminohexanoic acid;

100. 6-(C-α-D-glucopyranosyl)-5-phenylaminohexanoic acid; 101. l-(C-β-D-glucopyranosyl)hexane-2,6-diol;

102. 1 -(C-α-D-glucopyranosyl)hexane-2,6-diol;

103. 5-(C-β-D-glucopyranosyl)-4-ketopentanoic acid;

104. 5-(C-α-D-glucopyranosyl)-4-ketopentanoic acid;

105. 5-(C-β-D-glucopyranosyl)-4-hydroxypentanoic acid; 106. 5-(C-α-D-glucopyranosyl)-4-hydroxypentanoic acid; 107. 5-(C-β-D-glucopyranosyl)-4-aminopentanoic acid;

108. 5-(C-α-D-glucopyranosyl)-4-hydroxypentanoic acid;

109. 5-(C-β-D-glucopyranosyl)-4-phenylaminopentanoic acid;

110. 5-(C-α-D-glucopyranosyl)-4-phenylaminopentanoic acid; 111. l-(C-β-D-glucopyranosyl)pentane-2,5-diol;

112. l-(C-α-D-glucopyranosyl)pentane-2,5-diol;

113. 1 -(C-β-D-galactopyranosyl)-2-hydroxypropane;

114. l-(C-α-D-galactopyranosyl)-2-hydroxypropane;

115. 1 -(C-β-D-galactopyranosyl)-2-aminopropane; 116. l-(C-α-D-galactopyranosyl)-2-aminopropane;

117. 1 -(C-β-D-galactopyranosyl)-2-phenylaminopropane;

118. 1 -(C-α-D-galactopyranosyl)-2-phenylaminopropane;

119. ethyl 3-methyl-4-(β-D-galactopyranosyl)butyrate;

120. ethyl 3-methyl-4-(α-D-galactopyranosyl)butyrate; 121. 6-(C-β-D-galactopyranosyl)-5-ketohexanoic acid;

122. 6-(C-α-D-galactopyranosyl)-5-ketohexanoic acid;

123. 6-(C-β-D-galactopyranosyl)-5-hydroxyhexanoic acid;

124. 6-(C-α-D-galactopyranosyl)-5-hydroxyhexanoic acid;

125. 6-(C-β-D-galactopyranosyl)-5-aminohexanoic acid; 126. 6-(C-α-D-galactopyranosyl)-5-aminohexanoic acid;

127. 6-(C-β-D-galactopyranosyl)-5-phenylaminohexanoic acid;

128. 6-(C-α-D-galactopyranosyl)-5-phenylaminohexanoic acid;

129. l-(C-β-D-galactopyranosyl)hexane-2,6-diol;

130. l-(C-α-D-galactopyranosyl)hexane-2,6-diol; 131. 6-(C-β-D-galactopyranosyl)-5-ketopentanoic acid;

132. 6-(C-α-D-galactopyranosyl)-5-ketopentanoic acid;

133. 6-(C-β-D-galactopyranosyl)-5-hydroxypentanoic acid;

134. 6-(C-α-D-galactopyranosyl)-5-hydroxypentanoic acid;

135. 6-(C-β-D-galactopyranosyl)-5-aminopentanoic acid; 136. 6-(C-α-D-galactopyranosyl)-5-aminopentanoic acid; 137. 6-(C-β-D-galactopyranosyl)-5-phenylaminopentanoic acid;

138. 6-(C-α-D-galactopyranosyl)-5-phenylaminopentanoic acid;

139. 1 -(C-β-D-galactopyranosyl)pentane-2,6-diol;

140. l-(C-α-D-galactopyranosyl)pentane-2,6-diol; 141. l-(C-β-D-fucofuranosyl)propan-2-one;

142. l-(C-α-D-fucofuranosyl)propan-2-one;

143. l-(C-β-L-fucofuranosyl)propan-2-one;

144. l-(C-α-L-fucofuranosyl)propan-2-one;

145. 3'-(acetamido-C-β-D-glucopyranosyl)propan-2'-one; 146. 3'-(acetamido-C-α-D-glucopyranosyl)propan-2'-one;

147. l-(acetamido-C-β-D-glucopyranosyl)-2-hydroxypropane;

148. 1 -(acetamido-C-β-D-glucopyranosyl)-2-aminopropane;

149. l-(acetamido-C-β-D-glucopyranosyl)-2-phenylaminopropane;

150. 1 -(acetamido-C-α-D-glucopyranosyl)-2-phenylaminopropane; 151. ethyl 3-methyl-4-(acetamido-C-β-D-glucopyranosyl)butyrate;

152. ethyl 3-methyl-4-(acetamido-C-α-D-glucopyranosyl)butyrate;

153. 6-(acetamido-C-β-D-glucopyranosyl)-5-ketohexanoic acid;

154. 6-(acetamido-C-α-D-glucopyranosyl)-5-ketohexanoic acid;

155. 6-(acetamido-C-β-D-glucopyranosyl)-5-hydroxyhexanoic acid; 156. 6-(acetamido-C-α-D-glucopyranosyl)-5-hydroxyhexanoic acid;

157. 6-(acetamido-C-β-D-glucopyranosyl)-5-aminohexanoic acid;

158. 6-(acetamido-C-α-D-glucopyranosyl)-5-aminohexanoic acid;

159. 6-(acetamido-C-β-D-glucopyranosyl)-5-phenylaminohexanoic acid;

160. 6-(acetamido-C-α-D-glucopyranosyl)-5-phenylaminohexanoic acid; 161. l-(acetamido-C-β-D-glucopyranosyl)hexane-2,6-diol;

162. 1 -(acetamido-C-α-D-glucopyranosyl)hexane-2,6-diol;

163. 6-(acetamido-C-β-D-glucopyranosyl)-5-ketopentanoic acid;

164. 6-(acetamido-C-α-D-glucopyranosyl)-5-ketopentanoic acid;

165. 6-(acetamido-C-β-D-glucopyranosyl)-5-hydroxypentanoic acid; 166. 6-(acetamido-C-α-D-glucopyranosyl)-5-hydroxypentanoic acid; 167. 6-(acetamido-C-β-D-glucopyranosyl)-5-aminopentanoic acid;

168. 6-(acetamido-C-α-D-glucopyranosyl)-5-aminopentanoic acid;

169. 6-(acetamido-C-β-D-glucopyranosyl)-5-phenylaminopentanoic acid;

170. 6-(acetamido-C-α-D-glucopyranosyl)-5-phenylaminopentanoic acid; 171. l-(acetamido-C-β-D-glucopyranosyl)pentane-2,5-diol;

172. 1 -(acetamido-C-α-D-glucopyranosyl)pentane-2,5-diol.

As non-limiting illustrations of C-glycoside derivatives that are more particularly suitable for use in the invention, mention may be made especially of the following derivatives: - C-β-D-xylopyranoside-n-propan-2-one,

C-CC- D-xylopyranoside-n-propan-2-one,

C-β-D-xylopyranoside-2-hydroxypropane,

C-CC- D-xylopyranoside-2-hydroxypropane,

1 -(C-β-D-fucopyranoside)propan-2-one, - l-(C-CC-D-fucopyranoside)propan-2-one,

1 -(C-β-L-fucopyranoside)propan-2-one,

1 -(C-CC-L-fucopyranoside)propan-2-one,

1 -(C-β-D-fucopyranoside)-2-hydroxypropane,

1 -(C-CC-D-fucopyranoside)-2-hydroxypropane, - l-(C-β-L-fucopyranoside)-2-hydroxypropane,

1 -(C-CC-L-fucopyranoside)-2-hydroxypropane,

1 -(C-β-D-glucopyranosyl)-2-hydroxypropane,

1 -(C-α-D-glucopyranosyl)-2-hydroxypropane,

1 -(C-β-D-galactopyranosyl)-2-hydroxypropane, - l-(C-α-D-galactopyranosyl)-2-hydroxypropane,

1 -(C-β-D-fucofuranosyl)propan-2-one,

1 -(C-CC-D-fucofuranosyl)propan-2-one,

1 -(C-β-L-fucofuranosyl)propan-2-one,

1 -(C-α-L-fucofuranosyl)propan-2-one, - C-β-D-maltopyranoside-n-propan-2-one, C-α-D-maltopyranoside-n-propan-2-one, C-β-D-maltopyranoside-2-hydroxypropane,

C-α-D-maltopyranoside-2-hydroxypropane, isomers thereof and mixtures thereof. According to one embodiment, C-β-D-xylopyranoside-2-hydroxypropane or C- α-D-xylopyranoside-2-hydroxypropane, and better still C-β-D-xylopyranoside-2-hydroxy- propane, may be advantageously used for the preparation of a composition according to the invention.

According to one particular embodiment, the C-glycoside derivative may be C- α-D-xylopyranoside-2-hydroxypropane that is in the form of a solution containing 30% by weight of active material in a water/propylene glycol mixture (60%/40% by weight) such as the product manufactured by Chimex under the trade name Mexoryl SBB®.

Needless to say, according to the invention, a C-glycoside derivative corresponding to formula (I) may be used alone or as a mixture with other C-glycoside derivatives and in any proportion.

A C-glycoside derivative that is suitable for use in the invention may especially be obtained via the synthetic method described in document WO 02/051828.

The amount of C-glycoside derivative to be used in a composition according to the invention may vary within a wide range. A person skilled in the art can easily, on the basis of his general knowledge, determine the appropriate amounts.

A composition according to the invention may comprise a C-glycoside derivative in a proportion of from about 0.0001% to about 60% by weight of active material relative to the total weight of the composition, and in particular from about 0.0001% to about 50% by weight of active material, especially from 0.0001% to 40% by weight of active material, or even from 0.0001% to 30%, for example from 0.001% to 20% and more particularly from about 0.005% to about 10% by weight of active material and most particularly from about 0.05% to 5% by weight of C-glycoside derivative active material relative to the total weight of the composition. As stated previously, the present invention is also directed towards a device that is suitable for storing at least one C-glycoside derivative in a sterile environment. In such a device, the C-glycoside derivative may be formulated in the form of a powder, a solution or a dispersion.

In the case of a powder, the said powder will be mixed, before being used for the administration according to a mesotherapy technique, with a sterile liquid physiologically acceptable medium so as to formulate the C-glycoside in the form of a solution or dispersion that is compatible with administration by intra-epidermal and/or intradermal and/or subcutaneous injection.

Usually, the physiologically acceptable medium selected for forming an injectable C-glycoside fluid composition is chosen from water and isotonic saline aqueous solutions.

Thus, a composition according to the invention is generally used in the form of an aqueous or non-aqueous sterile isotonic solution, in the form of a dispersion, suspension or emulsion prepared, where appropriate, just before administration, using a sterile powder, for example a freeze-dried powder, which is then reconstituted in the form of an injectable sterile solution or a dispersion at the time of use.

As aqueous or non-aqueous medium that is suitable for use in the invention, examples that may be mentioned include water, ethanol, polyols such as glycerol, propylene glycol and polyethylene glycol, and mixtures thereof.

A viscosity that is suitable for the injectable solution may be obtained, for example, by using thickeners such as lecithin.

As isotonic agents that are suitable for preparing a composition that is suitable for use in the invention, mention may be made of sugars and sodium chloride.

A composition that is suitable for use in the invention may comprise any excipient usually used in the field of injectable sterile solutions, and in particular those usually used in the mesotherapy technique.

Thus, such a composition may comprise at least one or more additional active agents chosen, for example, from anti-ageing/anti- wrinkle agents, moisturizers, free-radical scavengers, slimming agents, agents acting on the capillary circulation, agents acting on the energy metabolism of cells, anti-acne agents, hyaluronic acid and antiglycation agents; NO-synthase inhibitors; agents that stimulate the synthesis of dermal or epidermal macro molecules and/or that prevent their degradation; agents that stimulate the proliferation of fibroblasts and/or keratinocytes, muscle relaxants and free-radical scavengers, and mixtures thereof.

According to one embodiment, these additional compounds may be capable in particular of exerting an anti-ageing effect. Among these compounds, mention may be made most particularly of vitamins, such as vitamin A, vitamin C, biotin, B vitamins, such as folic acid, panthenol and niacinamide, fruit acids, α-hydroxy acids, dehydroepiandrosterone (DHEA), micro- nutrients, hyaluronic acid suitable for administration by injection (chosen especially from non-crosslinked or weakly crosslinked hyaluronic acid), antioxidants, moisturizers, phosphatidylcholine, tensioning agents, such as 2-(dimethylamino)ethanol, procaine or 2- (diethylamino)ethyl 4-aminobenzoate), muscle relaxants and agents for improving the capillary circulation.

According to one particular embodiment, this or these additional compound(s) is (are) chosen from micronutrients, vitamins, especially B vitamin derivatives, such as panthenol, niacinamide or folic acid, biotin and in particular hyaluronic acid or a non- crosslinked or weakly crosslinked derivative thereof.

The hyaluronic acid used advantageously has a weight-average molecular weight ranging from 50 000 to 3 000 000 daltons, preferably ranging from 50 000 to 2 500 000 daltons and preferentially ranging from 500 000 to 2 000 000 daltons. As illustrations of different hyaluronic acid fractions, reference may be made to the document "Hyaluronan fragments: an information-rich system", R. Stern et al., European Journal of Cell Biology 58 (2006) 699-715, which reviews the listed biological activities of hyaluronic acid as a function of its molecular weight.

Hyaluronic acid may especially be provided by the company Hyactive under the trade name CPN (MW: 10 to 150 kDa), by the company Soliance under the trade name Cristalhyal (MW: l.lxlO⁶), by the company Bioland under the name Nutra HA (MW: 820 000 Da), by the company Bioland under the name Nutra AF (MW: 69 000 Da), by the company Bioland under the name Oligo HA (MW: 6100 Da) or by the company Vam Farma Cosmetica under the name D Factor (MW: 380 Da), by the company LCA Pharmaceutical under the trade name Hyaluderm, by the company Corneal under the trade name Juvelift Corneal, by the company Q-Med under the trade name Restylane Touch Line, or by the company Revitacare under the trade name Revitacare Biorevitalization. From 0.5% to 2.5% by weight of hyaluronic acid may advantageously be used in the composition.

The administration by intra-epidermal and/or intradermal and/or subcutaneous injection according to the invention is directed towards injecting a composition of the invention into an epidermal, dermo-epidermal and/or dermal region.

The process of the invention may be performed via any technique with an injection device that is suitable for intra-epidermal and/or intradermal and/or subcutaneous injection.

Thus, the injection may be performed through a needle usually used for performing an intra-epidermal and/or intradermal and/or subcutaneous injection, which is suitable for mesotherapy.

As examples of needles that are suitable for a process of the invention, mention may be made of needles with a diameter ranging from 0.26 to 0.4 mm and a length ranging from 4 to 13 mm. In particular, the needle that is suitable for use in the invention may have a diameter of 0.3 mm and a length of 6 mm.

The needle used is advantageously a single-use needle.

Advantageously, the needle is combined with a syringe or any other device for delivering the said injectable composition through the needle. According to one embodiment variant, a catheter may be intercalated between the needle and the syringe.

In a known manner, the syringe may be actuated manually by the practitioner or by a syringe support such as pistols.

A hydropneumatic-compression injection pistol with a high injection frequency may be used. Thus, an injection pistol that is suitable for use in the invention may be, for example, as described in patents EP 1 208 858 and US 5 300 029, which are introduced herein by reference.

For example, an injection pistol that is suitable for use in the invention may be

MesoMega®, Inderm PSI®, Pistor 4®, DHN3® or Rofil Meso Gun U225® sold by the company Rofil (Biophymed).

Whatever the injection device used, a composition of the invention is injected in the form of droplets. Advantageously, the droplets may have an average volume ranging from 0.01 to 0.2 ml and in particular from 0.05 to 0.15 ml.

According to one embodiment, the injection is advantageously repeated over all or part of a skin surface of an individual. Repetition of the injections makes it possible to create a layer so that the composition of the invention is uniformly distributed in the cutaneous area to be treated.

A composition of the invention may be advantageously injected into wrinkles and fine lines.

According to one particular embodiment, the cutaneous areas advantageously treated by a process of the invention may be the skin of the face and the neck, the neckline, the abdomen and the legs.

Thus, according to one embodiment, the step of administration by injection may be repeated over all or part of the surface of a face.

According to one embodiment, a process of the invention may be performed over several sessions spaced apart by a few days, for example 1, 2, 3, 4, 5 or 6 days to a few weeks, for example 1, 2, 3 or 4 weeks.

According to one embodiment, the step(s) of administration by injection may be advantageously performed using an injection pistol, especially a hydropneumatic- compression injection pistol with a high injection frequency as defined previously. There are two injection techniques: micropuncture (closely-spaced injections) or multi-point injection (injections in several more widely spaced points).

The repeated injections may also be performed point by point manually. The injection points may be spaced apart, for example, by a distance ranging from 5 mm to 1 cm. As stated previously, a process in accordance with the invention may be advantageously useful for preventing and/or treating the signs of ageing or photo-ageing of the skin.

According to one embodiment, a process in accordance with the invention may be useful for preventing and/or treating an impairment of the viscoelastic or biomechanical properties of the skin. According to one embodiment, a process in accordance with the invention may be useful for preventing and/or treating an impairment in the surface aspect and/or grain of the skin.

According to one embodiment, a process in accordance with the invention may be useful for preventing and/or treating a decrease in cellular energy metabolism.

Other characteristics and advantages of the invention will emerge from the examples that follow, which are given as non-limiting illustrations.

In the text hereinabove and hereinbelow, the proportions are given as weight percentages, unless otherwise indicated.

Example 1

Formula 1

The composition below is prepared, and is then packaged in a bottle under a sterile atmosphere.

This injectable composition is used for treating the face via the mesotherapy technique.

Formula 2 The composition below is prepared, and is then packaged in a bottle under a sterile atmosphere.

This injectable composition is used for treating the face via the mesotherapy technique.

Claims

1. Cosmetic process for aesthetic and/or repairing treatment of the skin of an individual, comprising at least one step of administering, to the said individual, according to a mesotherapy technique, a sterile fluid composition containing, in a physiologically acceptable medium, at least one C-glycoside derivative corresponding to the general formula (I) below:

X-R

^S (I) in which: - R represents a saturated C₁-C₁₀ and in particular a Ci -C₄ alkyl radical, which may be optionally substituted with at least one radical chosen from OH, COOH and COOR"₂ with R"₂ being a saturated Ci-C₄ alkyl radical,

- S represents a monosaccharide or a polysaccharide comprising up to 20 sugar units and in particular up to 6 sugar units, in pyranose and/or furanose form and of L and/or D series, the said mono- or polysaccharide possibly being substituted with a mandatorily free hydroxy 1 group, and optionally one or more optionally protected amine function(s), and

- X represents a radical chosen from the groups -CO-, -CH(OH)-, -CH(NH₂)-, -CH(NHCH₂CH₂CH₂OH)-, -CH(NHPh)- and -CH(CH₃)- and in particular a radical -CO-, -CH(OH)- or -CH(NH₂)- and more particularly a radical -CH(OH)-,

- the bond S-CH₂-X represents a bond of C-anomeric nature, which may be CC or β, and also the cosmetically acceptable salts thereof, solvates thereof such as hydrates, and optical and geometrical isomers thereof.

2. Process according to the preceding claim, which is useful for preventing and/or treating the signs of ageing or photo-ageing of the skin.

3. Process according to claim 1, which is useful for preventing and/or treating an impairment of the viscoelastic or bio mechanical properties of the skin.

4. Process according to claim 1, which is useful for preventing and/or treating an impairment of the surface aspect and/or grain of the skin.

5. Process according to claim 1, which is useful for preventing and/or treating a decrease in cellular energy metabolism.

6. Process according to any one of the preceding claims, in which S represents a monosaccharide chosen from D-glucose, D-xylose, L-fucose, D-galactose and D-maltose, and especially D-xylose.

7. Process according to any one of the preceding claims, in which the C- glycoside derivative is chosen from:

C-β-D-xylopyranoside-n-propan-2-one, C-CC- D-xylopyranoside-n-propan-2-one, C-β-D-xylopyranoside-2-hydroxypropane, - C-CC- D-xylopyranoside-2-hydroxypropane,

1 -(C-β-D-fucopyranoside)propan-2-one, 1 -(C-CC-D-fucopyranoside)propan-2-one, 1 -(C-β-L-fucopyranoside)propan-2-one, 1 -(C-CC-L-fucopyranoside)propan-2-one, - l-(C-β-D-fucopyranoside)-2-hydroxypropane,

1 -(C-CC-D-fucopyranoside)-2-hydroxypropane, 1 -(C-β-L-fucopyranoside)-2-hydroxypropane, 1 -(C-CC-L-fucopyranoside)-2-hydroxypropane, 1 -(C-β-D-glucopyranosyl)-2-hydroxypropane, - l-(C-CC-D-glucopyranosyl)-2-hydroxypropane,

1 -(C-β-D-galactopyranosyl)-2-hydroxypropane, 1 -(C-CC-D-galactopyranosyl)-2-hydroxypropane, 1 -(C-β-D-fucofuranosyl)propan-2-one, 1 -(C-CC-D-fucofuranosyl)propan-2-one, - l-(C-β-L-fucofuranosyl)propan-2-one,

1 -(C-CC-L-fucofuranosyl)propan-2-one, C-β-D-maltopyranoside-n-propan-2-one, C-α-D-maltopyranoside-n-propan-2-one, C-β-D-maltopyranoside-2-hydroxypropane, - C-α-D-maltopyranoside-2-hydroxypropane, isomers thereof and mixtures thereof.

8. Process according to any one of the preceding claims, in which the C- glycoside derivative is chosen from C-β-D-xylopyranoside-2-hydroxypropane and C-CC-D- xylopyranoside-2-hydroxypropane, and is more particularly C-β-D-xylopyranoside-2- hydroxypropane.

9. Process according to any one of the preceding claims, in which the said composition also comprises at least one additional compound chosen from micronutrients, vitamins, anti-ageing/anti-wrinkle agents, moisturizers, desquamating agents, anti- pollution agents and free-radical scavengers, slimming agents, agents acting on the capillary circulation, agents acting on the energy metabolism of cells, tensioning agents, depigmenting or pro-depigmenting agents, anti-acne agents, and hyaluronic acid, and mixtures thereof.

10. Process according to any one of the preceding claims, in which the said C- glycoside derivative is combined with at least one non-crosslinked or weakly crosslinked hyaluronic acid.

11. Process according to any one of the preceding claims, in which the administration is performed in an epidermal, dermo-epidermal and/or dermal region.

12. Process according to any one of the preceding claims, in which the step of administration by injection is repeated over all or part of a skin surface of the individual.

13. Process according to any one of the preceding claims, in which the step of administration by injection is repeated over all or part the surface of the face, the neck or the neckline of the individual.

14. Device that is suitable for storing at least one C-glycoside derivative and, where appropriate, for mixing it with a liquid physiologically acceptable medium, in a sterile environment, the said device comprising at least one sterile container and at least one C-glycoside placed in the said container, the said C-glycoside derivative having the general formula I below:

X-R

^S (I) in which:

- R represents a saturated Ci-Cio and in particular a Ci -C₄ alkyl radical, which may be optionally substituted with at least one radical chosen from OH, COOH and COOR"₂ with R"₂ being a saturated Ci-C₄ alkyl radical, - S represents a monosaccharide or a polysaccharide comprising up to 20 sugar units and in particular up to 6 sugar units, in pyranose and/or furanose form and of L and/or D series, the said mono- or polysaccharide possibly being substituted with a mandatorily free hydroxy 1 group, and optionally one or more optionally protected amine function(s), and

- X represents a radical chosen from the groups -CO-, -CH(OH)-, -CH(NH₂)-, -CH(NHCH₂CH₂CH₂OH)-, -CH(NHPh)- and -CH(CH₃)- and in particular a radical -CO-, -CH(OH)- or -CH(NH₂)- and more particularly a radical -CH(OH)-,

- the bond S-CH₂-X represents a bond of C-anomeric nature, which may be CC or β, and also the cosmetically acceptable salts thereof, solvates thereof such as hydrates, and optical and geometrical isomers thereof.

15. Device according to claim 14, in which the said C-glycoside derivative is as defined according to any one of claims 6 to 8.

16. Device according to claim 14 or 15, intended for a single use.