FR2945213A1 - Composition, useful e.g. to protect and/or regenerate dermis for use in skin to treat/prevent deterioration of dermis, comprises aqueous, alcoholic, or hydroalcoholic extract of aerial parts of a plant of genus Silene - Google Patents

Abstract

Composition comprises an aqueous, alcoholic, or hydroalcoholic extract of aerial parts of a plant of genus Silene. ACTIVITY : Dermatological; Vulnerary. MECHANISM OF ACTION : Collagen I synthesis stimulator.

Description

The present invention relates to cosmetic or dermatological compositions which have an action on the dermal cells, in particular in the human dermis. Various compositions having an action at the level of the dermis, and in particular compositions based on vitamin C, are known at the present time.

An object of the present invention is to provide novel compositions for cosmetic and dermatological use specifically for inhibiting or reducing the degradation of the dermis and regenerating the dermis in case of degradation.

To achieve this objective, the present invention provides a new type of cosmetic and dermatological composition, which uses a specific plant extract, namely an aqueous extract, alcoholic, or hydro-alcoholic aerial parts of a plant of the genus Silene.

Thus, according to a first aspect, the present invention relates to a composition for topical use for a cosmetic use related to a protection and / or regeneration of the dermis or for use for dermatological purposes to treat or prevent degradation of the dermis , characterized in that it comprises an aqueous, alcoholic or hydro-alcoholic extract of aerial parts of a plant of the genus Silene. The genus Silene belongs to the family Caryophyllaceae, which includes about 300 species, growing in the temperate regions of the Northern Hemisphere of the globe and in Southern Africa. The genus Silene includes plants with opposite leaves and white, pink, purple, red, sometimes whitish or yellowish flowers. The flower has a calyx with 5 sepals welded together, with longitudinal ribs and forming 5 teeth at the top. For more details, refer to La grande Flore in color by G. Bonnier. Vol 3. Ed Belin, p127-128, (1990) Among the various species of the genus Silene growing in France, mention may be made, inter alia, of the swollen silene (Silene vulgaris (Moench) Garcke, also known as Silene inflata Sm.), which is the most common species on the French territory and which grows up to 2600 m of altitude, or still the maritime silene (Silene maritima With.), whose characteristic habitat is the edge of sea. The plants of the genus Silene are commonly referred to by the generic term "silenes". In the present description, when "silene" is mentioned without more precision, this term refers to a plant of the genus Silene of an unspecified species.

Plants of the genus Silene are known to contain a number of interesting constituents. In particular, it has been described by Rochd et al. in Acta Bot. Gallica. Vol. 151. No. 2, pp. 173-180 (2004) that, like many Caryophyllaceae, the silenes are rich in saponosides (essentially quillaic acid glycosides), mainly in their roots, which explains why the plant was used as a substitute for soap . Silenes also contain ecdysteroids, which are non-water soluble phytosterols (Journal of Chromatography, A. Vol 935, pp. 309-319 (2001)). Nevertheless, to the knowledge of the Applicant, it has never been mentioned the presence in these plants compounds capable of ensuring an effect specifically in the dermis. In the context of the present invention, there is specifically used a particular extract of silene, which (1) is an aqueous, alcoholic or aqueous-alcoholic extract; and (2) is specifically obtained from aerial parts of the plant.

By "aqueous, alcoholic or aqueous-alcoholic extract" of aerial parts of silene is meant, in the sense of the present description, a composition which comprises all or part of the hydrophilic or water-soluble compounds which are present in the aerial parts of the plant, and which are extracted therefrom by means of a solvent selected from water, alcohols (preferably water-soluble), and mixtures of these solvents. The alcohols employed may be monoalcohols and / or polyols (especially diols or triols, such as glycols and glycerol).

According to an advantageous embodiment, the extract is obtained by using as extraction solvent: - water; or - an alcohol (preferably water-soluble); or - a mixture of several alcohols (preferably water-soluble); or - a mixture of water and at least one water-soluble alcohol. Preferably, the extraction solvent used to prepare the extract used in the context of the present invention is chosen from methanol, ethanol, propylene glycol, butylene glycol, glycerine, water, and mixtures of these solvents. A particularly suitable solvent is a water / alcohol mixture, preferably a water / ethanol mixture, preferably having an alcohol / water mass ratio of between 10/90 and 50/50, more preferably between 20/80 and 40/60, for example of the order of 30/70. According to a particular embodiment, the extract employed in the context of the present invention may be purified prior to its use in the composition. This purification may for example be carried out by preparative chromatography or by liquid / liquid extraction. On the other hand, the term "aerial parts" of a plant of the genus Silene refers to those parts of the plant which are exposed to the open air under conditions of normal growth of the plant (which excludes in particular the system root). Preferably, the silene extract employed in the context of the present invention exclusively comprises compounds derived from the aerial parts of the plant, excluding compounds from the other parts, in particular roots. The aerial parts from which is extracted the extract used in the context of the present invention generally comprise all or part of the stems and / or leaves of the plant. Preferably, these aerial parts comprise at least a portion of the stems and at least a portion of the leaves. In a particular embodiment, the aerial parts employed include both leaves and stems of the plant.

Preferably, the extract used in the context of the present invention is an extract of flowery aerial parts of a plant of the genus Silene. In this context, the extract is made from a flowering plant, the aerial parts employed then preferably comprising: all or part of the stems and / or all or part of the leaves; and - all or part of the flowers. According to a particular embodiment, the extract employed in the context of the present invention is obtained from a mixture of stems, leaves and flowers of a plant of the genus Silene in the flowered state.

Whatever the exact nature of the aerial parts used to produce the extract used in the context of the present invention, this extract is preferably obtained by grinding these aerial parts (freshly cut or previously dried), and then putting in contact the ground material obtained with a solvent of the aforementioned type, typically a water / alcohol mixture having an alcohol / water ratio of 20/80 and 40/60, for example an ethanol / water mixture having a weight ratio of 30/70. The extraction is preferably carried out by mixing the ground material and the solvent and subjecting this mixture to stirring so as to optimize the exchanges between the ground material and the extraction solvent. Preferably, the extraction is conducted at a temperature of 40 to 80 ° C, and for a duration which is typically of the order of 1 to 2 hours. According to a first embodiment, use is made, as the silene extract according to the invention, of the crude extract which is derived from the extraction described above, namely the medium as it is obtained directly at the end of the invention. extraction with one of the abovementioned solvents, this crude extract being optionally filtered prior to its use in the composition of the invention. In this first embodiment, the extract employed is in the form of a dispersion or a solution in a liquid medium including the aforementioned solvent. According to another embodiment, a dried extract obtained by subjecting the above-mentioned, preferably filtered, crude extract to a subsequent drying step, typically by atomization or lyophilization, according to techniques known per se, making it possible to preserve the integrity of the compounds present in the extract. The extract obtained according to this embodiment is generally in the form of a powder which is employed as such or taken up in a solvent or a dispersant to formulate the composition used according to the present invention.

Preferably, the plant of the genus Silene from which is extracted the extract used according to the present invention is the marine silene (Silene maritima). According to another conceivable embodiment, the plant of the genus Silene from which is extracted the extract used according to the present invention is the swollen silene (Silene vulgaris).

In the context of the present invention, the work of the inventors has made it possible to establish that the above-mentioned aqueous, alcoholic or hydro-alcoholic extracts, obtained from aerial parts of silene, in particular flowered, provide a specific effect at the level of the cells of the dermis, especially in humans. More specifically, the inventors have now demonstrated that by applying to the skin, topically, an aqueous, alcoholic or aqueous-alcoholic extract of the aerial parts of silene, in particular one of the abovementioned preferential extracts, is obtained, in particular in the to be a human, an action at the level of the dermal connective tissue, which makes it possible, among other things, to restart the process of proliferation of fibroblasts at the level of this tissue, to protect them against thermal or hydrous stresses, to stimulate synthesis collagen by dermal fibroblasts and protect the collagenous dermis network by inhibiting the expression of degradation enzymes. As a result, the silene extracts as used according to the invention are useful for the constitution of cosmetic and / or dermatological formulations for the protection, the regeneration, the restructuring, the redensification and / or the improvement of the qualities of the dermis. In this type of composition, the extract is generally associated with a suitable vehicle and possibly other active compounds.

The cosmetic and dermatological compositions comprising a silene extract according to the invention may especially be used to protect the dermal connective tissue, in particular human tissue, against the aggressions and aging effects and / or to stimulate the renewal of the connective tissue. dermal, as a preventive measure or during cicatricial processes. The dermal connective tissue plays an essential role in the support and maintenance of the cutaneous architecture. Changes in texture and composition are largely responsible for skin changes that occur during aging. The relief of the stratum corneum is, moreover, directly conditioned by the quality and density of the dermis that underlies it. It is indeed the dermal tissue that gives the skin its biomechanical qualities (compressibility, extensibility, stretchability, firmness ...). More than the epidermis, whose renewal is rapid and constant, the dermis undergoes significant age-related disorders, through the aging of its cells and its material. As they age, fibroblasts are less and less reactive and less proliferative. In addition, the constituent dermal macromolecules such as collagen fibers, elastic fibers, proteoglycans and glycosaminoglycans tend to degenerate and fragment. Their networks disorganize and reorient themselves parallel to the dermal-epidermal junction. The syntheses of these macromolecules are no longer provided by fibroblasts. These phenomena of alteration of the dermal tissue cause, on the surface, a lack of organization of the epidermis and in a more visible and direct way, a loss of firmness that can even lead to skin ptosis and / or the formation wrinkles.

By its external position, the skin is a particular organ which is particularly exposed and which undergoes environmental stresses (thermal variations, water variations, UV-related physical irradiations ...). These contribute and accelerate the appearance of the aforementioned phenomena.

According to a specific aspect, the subject of the invention is compositions comprising a silene extract of the aforementioned type which are used for a dermatological use. These dermatological compositions may in particular be used as formulations that are suitable for improving a normal or pathological healing process.

According to another aspect, the subject of the invention is the compositions comprising a silene extract of the aforementioned type and which are intended for cosmetic use. In this context, the invention also relates more specifically to the cosmetic use of compositions comprising silene extracts of the aforementioned type to fight against the effects on the dermis of skin aging, by preventing and / or reducing the effects of aging. cutaneous by an action on the level of the dermis; and / or by preventing and / or treating effects on the dermis related to external environmental aggressions, for example thermal and / or water stress. When used for cosmetic purposes, the compositions of the invention may especially be used: to prevent effects on the dermis of skin aging and external environmental aggressions; or to improve the aesthetic quality of a skin affected by the effects of aging and / or by external environmental aggressions. These uses of the compositions of the invention constitute, according to a particular aspect, still other objects of the present invention.

Preferably, the composition employed according to the present invention advantageously has at least one of the additional characteristics hereafter. In a composition according to the invention, the content of aqueous, alcoholic, or hydro-alcoholic extract of aerial parts of a plant of the genus Silene of the aforementioned type is typically between 0.001% and 3% by weight, this content being calculated by the ratio of the mass of the dry matter included in the extract, relative to the total mass of the composition. The term "dry matter" as used herein is understood in its most common sense, and refers to the mass of compounds present in the extract after any solvents removed. To obtain a particularly noticeable effect on the dermal connective tissue, it is generally preferable that the content of extract within the composition used according to the invention is greater than or equal to 0.001% and more preferably greater than or equal to 0.1. %. It is generally not required to use extract contents greater than 3% by weight to achieve marked effects on the dermis, but such extract levels are not excluded in the context of the present invention. Thus, typically, the concentration of silene extract in the composition is between 0.1 and 3% by weight for example between 0.5 and 2% by weight (in particular of the order of 1%). Nevertheless, according to another conceivable embodiment, it is possible to use, in the context of the present invention, a composition in which the content of silene extract can be much greater than 3% by weight, for example of the order of 50% by weight. mass or more (for example the crude extract as described above in the present description, as such or diluted in a solvent or dispersant solution, or the dried extract described above, taken up in a solvent or dispersant ).

Whatever its nature, the silene extract that is used in the composition according to the invention is generally used in conjunction with a vehicle that is acceptable, from a cosmetic and / or dermatological point of view, depending on the application envisaged for the composition, which can act as a solubilizer or dispersant of the extract and / or improve its application to the skin. This vehicle must in particular be adapted for the intended use and must be able to be brought into contact with the cells of the skin, in particular human skin, and in particular with the cells of the epidermis and the dermis without toxicity and irritation, undue allergic response. or similar and proportionate to a reasonable risk / benefit ratio. Any type of cosmetically or dermatologically acceptable vehicle known may be used in this context, it being understood that the vehicle employed in the context of the present invention is preferably of an aqueous or hydrophilic nature, so as to allow optimum dispersion of the compounds present in the invention. extract which are inherently hydrosoluble or hydrophilic. Thus, as a suitable vehicle in a composition according to the present invention, there may be mentioned in particular water, alcohols, in particular ethanol, propylene glycol, butylene glycol, glycerin, and mixtures of these compounds, as well as that the emulsions, in particular of water-in-oil or oil-in-water type, comprising one of these compounds as an aqueous phase.

Furthermore, the composition which is used according to the invention, which allows action on the skin by the topical route, is preferably in the form of an ointment, a cream, an oil or a milk. , an ointment, a powder, a soaked swab, a solution, a gel, a spray, a lotion or a suspension.

More generally, the compositions of the invention may especially be in the form of an oil-in-water or water-in-oil emulsion, a multiple emulsion, a microemulsion or an aqueous or hydroalcoholic gel. , cream, oil, or aqueous or hydroalcoholic lotion. Various aspects and advantages of the invention will emerge even more in view of the illustrative examples given hereinafter.

EXAMPLES: The extract employed In the following examples, a silene extract, hereinafter referred to as "E-extract", was used which was prepared under the conditions below. Flowering aerial parts (including stems, leaves and flowers) of maritime silene previously dried, then crushed, were contacted, with stirring, with a water / ethanol mixture having a water / ethanol mass ratio of 30/70 to a temperature of 50 ° C for 2 hours, whereby an extraction in the water / alcohol mixture of water-soluble and hydrophilic compounds initially present in the plant was obtained. The hydroalcoholic extract thus obtained (crude extract) was then filtered and dried, whereby a dried extract was obtained in the form of a powder.

The extract E used in the examples below was obtained by redispersing the dried extract in the form of a powder in ethanol (30% by volume ethanol), with 1 g of purified extract per 100 ml. This extract E was used in the following examples, which show, among other things, the effects of this extract on the revival of the fibroblast proliferation process, the protection of thermal stress, the stimulation and the synthesis of collagen. by fibroblasts and protection of the collagen network. When reference is made to a concentration of extract E in the media used in the examples below, this is calculated on the basis of the mass of the dry matter present in this extract (in other words not taking into account that the amount of solid dried extract introduced and not the solvent ethanol 30).

EXAMPLE 1 Effect on the proliferation of fibroblasts Normal human skin fibroblasts seeded in a monolayer were cultured for 24 hours in DMEM (Dulbecco's Modified Eagle's Medium) with a 10% (vol / vol) addition of newborn calf serum (SVNN). ). Serum depletion was then performed by placing the cultures in DMEM alone.

Extract E was then added to the culture medium to obtain an extract content in the medium of 10% (content expressed as mass of dry matter (in g) in the extract E relative to 100 ml of medium. of culture under SVNN). Following this treatment, the cell viability was evaluated by quantification of the metabolic activity of the mitochondrial dehydrogenases, by measurement of hydrolysis of MTT (MethylThiazoleTetrazolium) after respectively 1, 2 3 and 6 days of culture (J1, J2, J3 and J6).

For comparison purposes, cell viability was measured in parallel for: - a positive control carried out under the above conditions, with the difference that new born calf serum was added to the culture medium in place of the extract E, to reach a content of 5% (vol / vol) in serum in the medium; and a negative control, under the above conditions, with the difference that no addition has been made to the culture medium following the serum depletion. The results obtained are reported in Table 1 below, where they are expressed, for each day, as a percentage relative to the negative control, which serves as a 100% basis. Table 1 Negative control positive control extract EJ 1 100% 123% 115% J2 100% 133% 113% J3 100% 138% 115% J6 100% 200% 108% These results clearly illustrate the effects of the silene extracts according to the invention on the stimulation of the renewal of the dermal fibroblasts.

Example 2 Protection of fibroblasts in the face of water stress

In this example, tests were carried out showing the effect of the extract E on the treatment and inhibition of the adverse effects of heat stress on fibroblasts.

In each of the tests carried out, identical cultures of normal human fibroblasts, previously cultured in DMEM in an oven (37 ° C., 5% CO 2 and 85% relative humidity), were subjected to water stress, removing the cells of their culture medium and placing the cell mat thus deprived of its culture medium under a stream of air at 20 ° C for a period of 3h, before replacing the cells in DMEM oven at 37 ° C. 24 hours after the imposed stress, the residual viability of the cells was evaluated by quantification of the metabolic activity of mitochondrial dehydrogenases, by measurement of hydrolysis of MTT (MethylThiazoleTetrazolium). In a first series of tests, the fibroblasts were preventively treated with different amounts of extract E introduced 24 hours before the application of the stress in the culture medium, to respectively reach an extract content of 10-5% and 10-4% (content expressed as mass of dry matter (in g) in extract E relative to 100 ml of culture medium). In a second series of tests, the fibroblasts were treated 24 hours after the application of the stress by different amounts of extract E (to reach respectively the same contents of extract of 10-5% and 10-4% in the medium) . For comparative purposes, these tests were reproduced under the same conditions, but using instead of extract E, newborn calf serum (SVNN), added under the same conditions, ie respectively 24 hours before stress and 24 hours after stress to obtain a content of 10% (vol / vol) SVNN in the medium (positive controls). The tests were also reproduced under the same conditions as above, but this time without any addition either before or after the application (negative control, culture medium: DMEM alone). The results obtained are reported in Table 2 below, where they are expressed as a percentage relative to the negative control, which serves as a 100% basis.

Table 2 Viability of Positive Control Controls Extract E Extract E Fibroblasts Negative (SVNN) 10-5% 10-4% Curative Treatment 94% 104% 109% (24h before stress) 100% Preventive Treatment 136% 107% 119% (24h) after the stress) These results illustrate the effects of the silene extracts according to the invention on the inhibition of the effects related to heat stress and show in particular that the E extract can protect the metabolic activity of fibroblasts under stress conditions. water.

EXAMPLE 3 Action on the Collagen Synthesis by the Fibroblasts A series of tests was carried out, in which cultures were carried out in a monolayer of transformed human fibroblasts (line MRC-5), to which was added, in the culture medium, extract E at different concentrations. After 72 hours, the collagen I present was quantitatively determined by ELISA.

At the same time, a similar test (positive controls) was carried out by replacing the addition of extract E with a growth factor addition (TGFI3). A negative control was also performed without addition of either extract or growth factor. The results obtained with regard to the content of Collagen 1 (Coocaagen) are given in Table 3 below, where the concentration of additive indicated corresponds to the concentration in the culture medium of extract E (content expressed as mass of dry matter ( in g) in extract E relative to 100 ml of culture medium) or in added growth factor (in ng / ml). The CCollagen I / Ctemoin ratio corresponds to the collagen I concentration measured for a test considered relative to the collagen I concentration in the case of the negative control, which serves as a 100% base. Table 3 Concentration CCollagen I CCollagen I / Ctemoin in additive (in pg / mL) Negative control - 0.174 100% Positive control 20 ng / mL 0.320 184% (TG F (3) Extract E 1.7.10-3% 0.180 103% 3 , 4.10-4% 0.312 179% 6.8.10-5% 0.304 175% This table illustrates the properties of the silene extracts of the invention, which strongly stimulate the synthesis of collagen I.

EXAMPLE 4 Action on the Protection of the Collagenic Network Monolayer cultures of normal human fibroblasts were carried out, then treated with extract E (10-3%) and then stressed by UVA irradiations (23J / cm 2). After 24 h of further culture, cell viability was estimated by the WST1 assay, and supernatants were collected for analysis of MMP and TIMP expression patterns by the Quantibody method. This method allows a simultaneous assay of MMP1, 2, 3, 8, 9, 10 and TIMP1, 2 and 4. The results show that treatment with extract E inhibits the expression of MMP1 and 8 without modifying that of TIMPs . The silene extract is therefore of a nature to protect the connective tissue from possible enzymatic attacks of MMPs induced by environmental stresses. EXAMPLE 5 Day cream comprising an extract according to the invention

A day cream was prepared comprising the extract E tested in the previous examples, by mixing the following ingredients in the following proportions, given in percentage by weight, relative to the total weight of the composition:

water 51.275 glycerin 6.2 ethylhexyl cocoate 6 cornflower water 4 cetyl alcohol 4 methylsilanol sodium mannuronate 4 vegetable oils 11 glyceryl stearate 3 methyl sesquistearate glucose 2 hydrolyzed pectin 1.5 extract E (dry matter mass) 1 gum arabic 1 butter shea 1 talc 1 sorbitol 1 perfume 0.6 ethyl linoleate 0.3 vitamins 0.2 lecithin 0.2 carbomer 0.15 xanthan gum 0.15 phenoxyethanol 0.15 allantoin 0.1 sorbic acid 0.1 sodium hydroxide 0.05 tetrasodium EDTA 0.025

Claims (10)

1. A composition for topical use for a cosmetic use related to a protection and / or regeneration of the dermis for use for dermatological purposes for treating or preventing degradation of the dermis, characterized in that it comprises an aqueous extract, alcoholic, or hydro-alcoholic of aerial parts of a plant of the genus Silene. 2. Composition according to claim 1, in which the extract is an aqueous, alcoholic or hydro-alcoholic extract of floral overhead parts of a plant of the genus Silene. 3. The composition of claim 1 or claim 2 wherein the plant of the genus Silene is the marine silene (Silene maritima). 4. The composition of claim 1 or claim 2 wherein the plant of the genus Silene is the swollen silene (Silene vulgaris). 5. Composition according to one of Claims 1 to 4, characterized in that the extract is obtained by grinding the aerial parts of the plant of the genus Silene and then bringing the resulting ground material into contact with a solvent chosen from methanol. ethanol, propylene glycol, butylene glycol, glycerine, water and mixtures of these solvents, preferably at a temperature of between 40 and 80 ° C. and for a duration typically of the order of 1 to 2 hours. 25 6. A composition according to one of claims 1 to 5 wherein the composition comprises the extract in a content of between 0.001% and 3% by weight, this content being calculated by the ratio of the mass of the dry matter included in the present invention. extract, based on the total mass of the composition. 7. Composition according to one of claims 1 to 6 for its dermatological use to improve a healing process, normal or pathological. 30 8.- Cosmetic use of a composition according to one of claims 1 to 6 to combat the effects on the dermis of skin aging. 9. - Cosmetic use according to claim 8 for preventing the effects on the dermis of skin aging and external environmental aggressions. 10.- cosmetic use according to claim 8 for improving the aesthetic quality of a skin affected by the effects of aging and / or external environmental aggressions.