FR2876283A1 - COSMETIC COMPOSITION COMPRISING A SACCHARIDIC COMPOUND HAVING A REPEATED PATTERN RICH IN RHAMNOSE, AND ITS USE IN COSMETICS FOR AN ANTI-AGING SKIN ACTION - Google Patents

Abstract

The present invention relates to a new cosmetic composition comprising a saccharide compound exhibiting a repeated unit rich in rhamnose and its use in particular in products for topical application, for which an anti-aging activity is sought, in particular cosmetic products with an anti-aging effect. , as well as its manufacturing process.

Description

The present invention relates to a new cosmetic composition

  comprising a saccharide compound having a repeat unit rich in rhamnose and its use especially in topically applied products, for which an anti-aging activity is sought, in particular anti-aging cosmetic products, as well as its manufacturing process.

  During aging the skin thins on average about 7% every ten years (Skin thickness changes in normal aging skin, Branchet et al., Gerontology, 1990, 36: 28-35). This cutaneous thinning concerns the epidermis and the dermis. This loss of tissue represents an approximately equivalent loss of cells, epidermal keratinocytes and dermal fibroblasts. The keratinocytes present in the epidermis, as well as the fibroblasts present in the dermis are known to elaborate proteolytic enzymes which contribute to an important cutaneous thinning (Dr L. ROBERT: Aging, CNRS, Belin, 1994, Dr L. ROBERT: Aging, facts and theories, Dominos, Flammarion, 1995).

  However, different macromolecules of the extracellular matrix (ECM) behave differently. Loss of collagen fibers has been shown to be less rapid than total skin tissue loss. Conversely, fibronectin biosynthesis has been shown to increase in skin with age and fibroblasts in culture as a function of the number of passages. The elastic fibers of the papillary dermis, forming a vertical network, are progressively degraded. A majority of horizontal elastic fiber networks predominate with age in the dermis. The surface density of elastic fibers, quantified by image analysis, has been shown to increase with age. This marked increase in the surface density of elastin with age, however, is accompanied by a gradual decline in the elasticity of the skin. These data show the complexity of age-dependent changes in skin tissue and macromolecular composition.

  One of the parameters mentioned above is the thickness of the skin which decreases with age. The two layers of dermis and epidermis are affected by this evolution.

  In recent years, numerous studies have sought to obtain active compounds against certain effects of skin aging. A first goal is to get a thickening of the skin. Another goal is to slow down this process of thinning skin and restore the normal thickness of the dermis.

  Saccharides and polysaccharides are substances well known in cosmetics, especially for their moisturizing properties.

  Rhamnose-rich oligosaccharides and polysaccharides act on keratinocyte adhesion to rhamnose lectins and inhibition of polynuclear adhesion to keratinocytes. They thus make it possible to modulate the propagation of the cellular messages and to consequently attenuate the consecutive irritative reactions (anti-inflammatory effect).

  Surprisingly and unexpectedly, it has now surprisingly been found that a saccharide compound having a repeating rhamnose-rich pattern exhibits significant activities on various skin components, resulting in a truly visible anti-aging result.

DESCRIPTION

  Thus, the subject of the present invention is a skin anti-aging cosmetic composition, characterized in that it comprises at least one saccharide compound having a repeat unit rich in rhamnose and a cosmetically acceptable excipient.

  By repeating rhamnose-rich motif is meant according to the present invention a repeating unit in which at least 40% of the molecules are rhamnose molecules.

  Preferably, the repeating rhamnose-rich unit of the saccharide compound also comprises glucose and glucuronic acid.

  Even more preferably, the rhamnose-rich repeating unit of the saccharide compound comprises at least three rhamnoses, a glucose and a glucuronic acid.

  More particularly, the repeating unit rich in rhamnose is:> 3) - (3-L-Rhap- (1-> 4) - (3-D-Glcp- (1-> 2) aL-Rhap (1-> 4) ) aD-GlcpA (1-3

T

  a-L-Rhap where Rhap is Rhamnose, Glcp is glucose and GlcpA is glucuronic acid.

  According to one aspect of the invention, the saccharide compound rich in rhamnose is an oligosaccharide.

  By oligosaccharide is meant according to the present invention a molecule formed by the polymerization of 1 to 10 repeat units bonded by osidic bonds.

  Preferably, the oligosaccharide has a molecular weight of about 5 kDa.

  By neighboring molecular weight is meant according to the present invention a molecular weight of plus or minus 20% relative to the molecular weight cited.

  In another aspect of the invention, the rhamnose-rich saccharide compound is a polysaccharide.

  By polysaccharide is meant according to the present invention a molecule formed by the polymerization of more than 10 repeating units, linked by osidic bonds.

  Preferably, the polysaccharide has a molecular weight greater than 30 kDa, even more preferentially close to 500 kDa.

  The saccharide compound having a repeating unit rich in rhamnose is particularly suitable as active in a cosmetic composition including anti-aging (topical application).

  The cosmetically acceptable excipient may be any excipient among those known to those skilled in the art in order to obtain a composition according to the invention in the form of a cream, a lotion, a gel or an ointment. , etc., optionally in the form of an emulsion with further components known to those skilled in the art, for improving, modifying or stabilizing the composition from a cosmetic point of view.

  By way of example, the composition according to the invention may comprise excipients well known to those skilled in the art for the formulation of composition intended for topical application. Such excipients may be selected from the group consisting of skin structuring agents (such as squalene and sphingolipids), humectants (such as glycerin and hydroxy prosilan C), emollients (such as butylene). glycol and cetyl lactate), silicones (such as cyclomethicone), sun protection agents (such as parsol 1789 and Eusolex 6300), emulsifiers (especially Carbopol 1342 combined with triethanolamine and soy lecithin) , thickeners (especially xanthan gum), sequestering agents (especially EDTA), antioxidants (such as BHT), fragrances, preservatives, water and mixtures thereof.

  The saccharide compound rich in rhamnose is used in a proportion of between about 0.1 and 10% by weight, relative to the total weight of the cosmetic composition.

  Of course, the operating conditions for preparing the cosmetic composition according to the invention are part of the general knowledge of those skilled in the art.

  The present invention also relates to the use of the cosmetic composition intended for an anti-aging action on the skin.

  This anti-aging effect of the composition is due to the properties of the saccharide compound acting on the surface keratinocytes of the skin, the fibroblasts of the dermis, in particular by the cell proliferation of fibroblasts, by the inhibition of fibroblast elastase activity, which is responsible for the enzymatic degradation of the elastic fibers of the skin, and by the inhibition of the free radical degradation of hyaluronic acid (or hyaluronan) which ensures in the dermis a fundamental function of filling, cohesion, and hydration skin. The anti-aging effect of the composition is also reflected by the increase in collagen synthesis, and the thickness of the dermis and epidermis.

  The present invention also relates to a method for the cosmetic treatment of the skin, characterized in that a cosmetic composition comprising at least one saccharide compound according to the present invention is applied to the skin.

  The present invention also relates to a method for manufacturing a saccharide compound, according to the present invention, of molecular weight close to 5 kDa, characterized in that it comprises the following steps: obtaining a polysaccharide, starting from a Klebsiella strain controlled enzymatic hydrolysis of the polysaccharide obtained in the previous step.

  Preferably, the polysaccharide obtained in the first step of the process according to the invention is rich in rhamnose, and even more preferably has a molecular weight in the region of 50 kDa. Preferably, the polysaccharide is obtained in the process according to the present invention from of a strain of Klebsiella planticola.

  Other advantages and characteristics of the invention will appear better on reading the examples given by way of illustration and not limitation.

LEGEND OF FIGURES

  Figure 1: elastase activity of human skin fibroblasts at different passages with or without a 5 kDa rhamnose-rich oligosaccharide.

EXAMPLES:

  The following examples summarize the data obtained by the inventors on the rhamnose-rich polysaccharide (hereinafter referred to as polysaccharide) and its rhamnose-rich oligosaccharide of 5 kDa (referred to hereinafter as oligosaccharide) according to the present invention. Both products were supplied by BioEurope Solabia.

  Each parameter of these two saccharide compounds, in relation to aging of the skin, was tested by a specific method.

  These parameters are: cell proliferation, protection against free radicals in an aqueous medium, the effect on collagen synthesis and finally, the effect on cellular activity of elastase.

  Example 1 Effect on Cellular Proliferation Normal human dermal fibroblasts are cultured under standard conditions. The polysaccharide and the oligosaccharide are added to the culture medium and their effects on cell proliferation are evaluated by MTT assay and cell counting.

  The MTT test makes it possible to evaluate the oxidative metabolism of the cell and gives a good estimate of their number. The cell count is performed by an electronic counter.

  The results show for the polysaccharide at a concentration of 1 gg / ml, a stimulation of cell proliferation of 75%, very significantly (P <0.0005).

  Stimulation by the oligosaccharide of 5 kDa is still higher: 82% increase in cell proliferation, also very significantly (P <0.0005).

  EXAMPLE 2 Protection against free radicals The protection against free radicals is evaluated by viscometry. The loss of viscosity of a hyaluronan solution is recorded after addition of a reagent producing free radicals: the Udenfriend reagent. The free radicals produced by this reagent attack the hyaluronan and thereby decrease the viscosity of the solution.

  The presence of a protector such as the polysaccharide or its 5 kDa oligosaccharide can inhibit or reduce the effects of free radicals.

  The results show an increased protection of 55% with the polysaccharide at a concentration of 10 g / ml.

  The 5 kDa oligosaccharide gives an increased protection of 27% at a concentration of 10 g / ml. The difference in protection observed between the polysaccharide and its oligosaccharide raises the question of the relationship between the size of the saccharide compound and its protective capacity. A large polysaccharide appears to be more effective for free radical protection.

  Example 3 Effect on Collagen Synthesis Collagen synthesized in a cell culture is evaluated by a colorimetric method. The specific colouration of collagen is done by a red sine dye. After two days of culture with the polysaccharide or its oligosaccharide, the cell cultures are fixed, stained, and the color density is evaluated by colorimetry after solubilization of the collagen.

  The results show that the rhamnose-rich polysaccharide at a concentration of 1 gg / ml produces a stimulation of collagen synthesis of 31% while its oligosaccharide induces a weaker stimulation, of only 17%.

  EXAMPLE 4 Effect on fibroblast elastase activity: 1) Method The elastase activity of cell extract is determined by the hydrolysis of a chromatogenic substrate. Reading the optical density of the reaction medium after the action of the cell extracts on the substrate makes it possible to calculate the elastase activity of the cell extracts. The cells used are normal fibroblasts of the human dermis, at successive passages (through passage 15 = P5 to p15).

  In the present experiment, three active ingredients were tested: the polysaccharide, its oligosaccharide of 5kDa.

  2) Results The results, described in FIG. 1, show an evolution of the elastase activity of the fibroblasts as a function of the passages, up to the fifteenth passage.

  Until the 13th passage, the elastase activity is progressively upregulated during in vitro aging. From the 13th to the 14th passage, the elastase activity decreases and remains stable until the 15th passage. Nevertheless the trend curve established by the computer continues to increase.

  Among the substances tested, only the 5kDa oligosaccharide produced a negative regulation of the elastase activity at all the successive passages. FIG. 1 shows the passage-dependent evolutions of the elastase activity in the presence of the oligosaccharide, added to the fibroblast cultures, at a concentration of 10 g / ml throughout the culture period.

  It can be seen that the elastase activity is upregulated by the fibroblasts much less at each passage in cultures comprising the oligosaccharide.

  This inhibition of the upregulation of the elastase activity is calculated from the initial slope of the control culture curve and the curve of the oligosaccharide treated culture.

  This inhibition is approximately 65%. At the last pass, the control curve shows an increase in its slope. Even at these high values of elastase activity expressed by the cell, the inhibition is close to 60%. These results confirm that the oligosaccharide interferes with the regulation of the expression of elastase activity by fibroblasts by very strongly attenuating its positive regulation linked to.

  3) Conclusion The constant presence of the 5kDa oligosaccharide in the fibroblast culture at a concentration of 100 g / ml, produces a very strong negative regulation of the expression of the elastase activity of the fibroblasts of the human skin. This effect is much more important than the already secreted elastase inhibition.

  The mechanism of action concerns the active biosynthesis of elastase endopeptidases (essentially MMP-2 and -9). It has been shown previously and confirmed by this experiment that fibroblasts positively regulate elastase activity during aging in vitro (and also in vivo). This positive regulation with Page is considerably diminished by the 5 kDa oligosaccharide.

  These results justify the use of this oligosaccharide in future anti-aging preparations. It also seems highly probable that the constant application of a preparation containing this oligosaccharide can considerably reduce the loss of skin thickness related to time.

  Conclusions of Examples 1 to 4: The results of these four examples taken together show that the rhamnose-rich polysaccharide and its 5kDa oligosaccharide are important active ingredients for the preparation of skin anti-aging cosmetic products, since they allow an increase of cell proliferation, protection against free radicals, an increase in collagen synthesis and a decrease in fibroblast elastase activity.

Claims (14)

claims   1. Anti-aging cosmetic composition of the skin characterized in that it comprises at least one saccharide compound having a repeating unit rich in rhamnose and a cosmetically acceptable excipient.   2. Cosmetic composition according to claim 1 characterized in that the repeat unit rich in rhamnose also comprises glucose and glucuronic acid.   3. Cosmetic composition according to claim 1 characterized in that the repeat unit rich in rhamnose comprises at least three rhamnoses, a glucose and a glucuronic acid.   4. Cosmetic composition according to any one of Claims 1 to 3, characterized in that the repeating unit rich in rhamnose is: 3) - (3-L-Rhap- (1-> 4) - (3-D-Glcp) (1- + 2) aL-Rhap (1-4) aD-GlcpA (1-3-1 aL-Rhap 5. Cosmetic composition according to any one of claims 1 to 4 characterized in that the saccharide compound rich in rhamnose is an oligosaccharide.   6. Cosmetic composition according to claim 5, characterized in that the oligosaccharide has a molecular weight close to 5 kDa. 7. Cosmetic composition according to any one of claims 1 to 4 characterized in that the saccharide compound rich in rhamnose is a polysaccharide.   8. Cosmetic composition according to claim 7, characterized in that the polysaccharide has a molecular weight greater than 30 kDa, preferably close to 500 kDa. 9. Cosmetic composition according to any one of claims 1 to 8 characterized in that it is suitable for topical application especially in that it is in the form of a cream.   10. Cosmetic composition according to any one of claims 1 to 9 characterized in that the saccharide compound rich in rhamnose is used in a proportion of between 0.1 and 10% by weight, relative to the total weight of the composition.   11. Use of the cosmetic composition according to any one of claims 1 to 10 characterized in that it is intended for an anti-aging action of the skin.   12. Cosmetic skin treatment method, characterized in that a cosmetic composition comprising at least one saccharide compound as defined in any one of Claims 1 to 10 is applied to the skin.   13. Process for the production of a saccharide compound of molecular weight close to 5 kDa according to any one of claims 1 to 6 and 9 and 10, characterized in that it comprises the following steps: - obtaining a polysaccharide, from a strain of Klebsiella planticola; controlled enzymatic hydrolysis of the polysaccharide obtained in the previous step.   14. A method of manufacturing a saccharide compound according to claim 13 characterized in that the polysaccharide obtained in the first step is as defined in claims 7 or 8.