FR2967063A1 - Non-therapeutic cosmetic use of at least one pomegranate extract, as agent for firming skin of a subject, who has weight modification prior to and/or after an aesthetic surgery and to prevent and/or treat sagging skin - Google Patents

Abstract

Non-therapeutic cosmetic use of at least one pomegranate extract, as agent for firming skin of a subject, who has weight modification prior to and/or after an aesthetic surgery, is claimed ACTIVITY : Dermatological; Anabolic. MECHANISM OF ACTION : Glycosaminoglycan synthesis stimulator.

Description

The present invention is in the field of skin care, topical products, food supplements or functional foods for the care of the skin.

The human skin consists of three compartments namely a superficial compartment, the epidermis, the dermis and a deep compartment, the hypodermis. This last compartment essentially consists of a type of cells specialized in the accumulation and storage of fats, the adipocytes. The hypodermis is the energy reservoir of the body.

The natural human epidermis is composed mainly of three types of cells which are keratinocytes, melanocytes and Langerhans cells. Each of these cell types contributes by its own functions to the essential role played by the skin.

The dermis provides the epidermis with a solid support while also being its nurturing element. It consists mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elastin and a substance called fundamental substance, components synthesized by fibroblasts.

The extracellular matrix (ECM) of human skin consists of various macromolecules responsible for the mechanical strength of the skin, its suppleness and elasticity, as well as physiologically important functions (hydration, thermoregulation and regulation of skin permeability). ).

The macromolecules of the MEC have been arbitrarily classified into four families. The first two consist of fibrous and structural macromolecules, collagens and elastin, while the other two are glycoconjugates (glycoproteins and proteoglycans).

During weight loss and in particular during slimming diets, rapid destocking of the adipocytes results in a significant decrease in the tension exerted by the hypodermis on the support tissues. Therefore, the dermis is no longer under tension, the connective tissue gradually loses its cohesion and this mainly by depolymerization of proteoglycans and by decreasing the amount of glycosaminoglycans.

It is thus clear from reading the foregoing the importance of glycosaminoglycans in the structure of the tissues, particularly of the skin and / or mucous membranes, and the importance of combating their decrease, so as to fight in particular against the appearance of soft skin.

Unexpectedly, the inventors have found that the use of pomegranate extract was particularly effective, to stimulate the synthesis of glycosaminoglycans in the skin. By this mechanism and in particular in the adult, this use can thus make it possible to firm loose skin, less firm skin following changes in weight (such as in diets, pregnancies ...) or in the accompaniment cosmetic surgery gestures such as face lift or fillers injections.

Pomegranate (pomegranate) is the fruit of the pomegranate (Punica granatum), a shrub of the family Lythraceae.

This fruit, cultivated for several thousand years, has many merits, some of which have been known for a very long time. Its beneficial effects on hypertension have been described as well as its preventive effects of cancers of the prostate and breast or delaying the deterioration of cartilage which is responsible for osteoarthritis.

Its firming effect had previously been described only for skins having suffered the effects of age (chronological aging) and / or the sun (photo-aging). This is for example the case in US patent application 2003/091665. In the application KR 20030055950 is described the topical use of a pomegranate extract to prevent or treat the effects of age.

However, it has never been mentioned in the prior art the firming effect of the pomegranate on skins having undergone a weight change or having undergone an act of cosmetic surgery.

Thus, the present invention relates, in one of its aspects, to the cosmetic use of an effective amount of at least one pomegranate extract, as a firming agent for the skin of a subject having undergone a change in weight or previously, simultaneously and / or after an act of cosmetic surgery.

This firming action comes from the stimulation by this pomegranate extract of the synthesis of glycosaminoglycans in the skin. This neosynthesis of GAGs allows the connective tissue to improve its cohesion and thus ensure all its role in supporting the skin.

By "effective amount" is meant in the sense of the present invention, an amount sufficient to achieve the expected effect.

By "pomegranate extract" is meant as well fruit extracts, Punica granatum seed extracts and mixtures thereof in all proportions. Advantageously, using a fruit extract - or pomegranate extract - this extract can come from all parts of the pomegranate. The preferred pomegranate extract according to the present invention will be a whole fruit extract or even more preferably a whole fruit juice (often called "pomegranate fruit juice extract" by the suppliers).

The pomegranate extract can be obtained from any part of the pomegranate and in particular from the fruit including the seed.

By extract is meant both a crude mixture of parts of the plant roughly reduced in pieces and the extraction solvent that more or less elaborate fractions or preparations of the active principles solubilized during extraction. A total extract can be used, that is to say an extract comprising all the fractions present in the parts of Punica granatum, possibly devoid of cellulosic (ligneous) parts. According to another embodiment of the invention, at least one extract enriched in certain fractions will be used.

The extract can be obtained by any method for preparing a plant extract known to those skilled in the art. In particular, the extract may be obtained by maceration of the part of the plant in water, or in a solvent composed of a mixture of water and an organic solvent, for example water-alcohol, or water- acetone, or water-propylene glycol, or water-butylene glycol. The plant / solvent ratio may vary for example and without limitation from 1/4 to 1/20.

Advantageously, the preparation of the extract begins by grinding the parts of the plant followed by maceration in the extraction solvent for several hours. Extraction can be performed with stirring to improve performance. The extraction can be carried out at ambient temperature or by increasing the temperature, for example at 50 ° C. or else at 60 ° C. Once extraction is complete, the solution is filtered.

The solution thus obtained can be concentrated by any method known to those skilled in the art. Also the solution obtained can be lyophilized by any conventional freeze-drying method. A powder is thus obtained.

The extraction from the pomegranate fruit including the seed can result, according to a particular method of realization, in the preparation of an essential oil. The extract in the form of a concentrated solution, as well as the extract in powder form, as well as the extract in the form of an essential oil may be taken up in a suitable medium for oral consumption for humans.

According to an advantageous embodiment of the invention, the extract is chosen from aqueous extracts and alcoholic or hydro-alcoholic extracts of Punica granatum. The extract can be introduced in the form of a freeze-dried powder, a liquid or an oil and / or if necessary in a concentrated form.

Such extracts are for example marketed by the company DRACO Natural Products under the trade names "Pomegranate Seed Oil" or "Pomegranate Powdered Extract, 40%" or by the company Naturex under the name "Pomegranate fruit juice extract" or "Pomegranate extract 40%", or by the company MMP Inc. under the trade name "Pomegranate Juice extract E40" or by the company Blue California under the trade name "Pomegranate Extract 20 70%", or by the company Guillin Layn Natural Ingredients under the trade name "Pomegranate Seed PE" or registered for example with CAS number 84961-57-9.

It is understood that the choice of pomegranate extracts is made taking into account the purpose of the composition comprising them, that is to say intended for topical application or transcutaneous administration or oral administration or administration by air.

By the word "prevent" is meant to "reduce the risk of developing". By the term "treat", unless otherwise indicated, is meant any action to improve the comfort, well-being of an individual, this term therefore covers as well alleviate, relieve than cure.

This use is particularly relevant for preventing and / or treating relaxed skin, said relaxation being preferentially due to a modification and / or a decrease in the level of glycosaminoglycans in the dermis.

This use may also be relevant for maintaining and / or restoring the biomechanical properties (especially the elasticity and / or the tone) of the skin and / or the elasticity and / or the tonicity and / or the firmness of the skin and / or to reduce the appearance of cellulite and / or the appearance of orange peel and / or to treat stretch marks or prevent their appearance.

The change in weight and especially the weight loss will preferably be due to a slimming diet or pregnancy.

The act of cosmetic surgery will preferably be chosen from facelift, liposuction and the injection of fillers.

The term "lifting" generally refers to all operations intended to correct the sagging of the skin, and for example the sagging cheekbones and hollows in the middle of the cheeks.

A facelift can also be performed, if necessary, by an act of cosmetic surgery. For the purposes of the invention, the term "cosmetic surgery" is intended to denote surgery intended in particular to correct congenital (nose, ears, chin) or acquired puberty (breast hypotrophy, localized fat overload) physical disgraces in pregnancies (deformation of the abdominal wall) or aging (face, eyelids, neck, breasts). As an act of cosmetic surgery, one can also cite, without limitation, blepharoplasty, abdominoplasty (or tummy tuck), rhinoplasty, breast plasty, liposuction or lipostructure. Injections of tensor products such as botulinum toxins (eg BotoxO) can also be used to reduce wrinkles on the face.

The principle of liposuction in cosmetic surgery is to introduce cannulas in very small incisions, these cannulas being connected to a closed circuit in which a negative pressure will be created, thus allowing the grease to be sucked into the targeted zones.

Examples of "fillers" (otherwise known as "fillers") may be cited: bovine collagen (eg ZydermO, ZyplastO), calcium hydroxylapatite, hyaluronic acid (eg RestylaneO, HylaformO, SculptraO), human collagen such as AutologenO, CosmoDermO, CosmoPlastO and DermalogenO, fat, synthetic fillers like ArtecollO and JUVÉDERMO Injectable Gel®. Tensor products such as botulinum toxins (eg BotoxO) can also be used in combination with fillers.40 The effective amount of pomegranate extract will preferably be used at a content ranging from 0.0001 to 1000 / 0 by weight, especially from 0.001 to 200/0 by weight or 0.01 to 150/0 by weight, more particularly from 0.1 to 100/0 by weight, and even more preferably from 0.5 to 50/0 by weight, weight relative to the total weight of the composition containing it.

The content of pomegranate extract in the compositions for the topical route will preferably be from 0.001 to 200% by weight, more preferably from 0.1 to 100% by weight, and even more preferably from 0.5 to 50% by weight. weight relative to the total weight of the composition containing it.

The content of pomegranate extract in the compositions for the oral route will preferably be between 15 and 1000/0 by weight. In oral administration, the composition may therefore consist, in a particular embodiment of the invention, only pomegranate extract. However, this pomegranate extract content will be more preferably between 15 and 600/0 by weight and even more preferably between 15 and 300/0 by weight relative to the total weight of the composition containing it.

Another subject of the invention is the use of pomegranate, for the preparation of a cosmetic or pharmaceutical composition for topical application or oral and / or parenteral administration intended to prevent and / or treat disorders of the skin related to a decrease in glycosaminoglycans.

The present invention relates to a composition, in particular a cosmetic and / or dermatological composition intended more particularly for the prevention and / or treatment of skins qualified as loose skins. This composition, preferably useful as defined above, may comprise, in a physiologically acceptable medium, an effective amount of at least one pomegranate extract associated with at least one agent stimulating the macromolecules of the dermis or preventing their degradation.

As agent stimulating the macromolecules of the dermis or preventing their degradation, mention may be made of those which act: either on the synthesis of collagen, such as synthetic peptides such as iamin, the biopeptide CL or palmitoyloligopeptide marketed by SEDERMA; peptides extracted from plants, such as the soy hydrolyzate marketed by the company Coletica under the trade name Phytokine®; and plant hormones such as auxins and lignans. or on the synthesis of elastin, such as the extract of Saccharomyces cerevisiae sold by the company LSN under the trade name Cytovitin®; and the algae extract Macrocystis pyrifera marketed by SECMA under the trade name Kelpadelie®; or on the synthesis of glycosaminoglycans, such as the product of fermentation of milk with Lactobacillus vulgaris, sold by BROOKS under the trade name Biomin yogourth®; the extract of the brown alga Padina pavonica marketed by ALBAN MÜLLER under the trade name HSP3®; and the Saccharomyces cerevisiae extract available in particular from the company Silab under the trade name Firmalift® or from the company LSN under the trade name Cytovitin®; or on the synthesis of fibronectin, such as the extract of zooplankton Satina marketed by SEPORGA under the trade name GP4G®; yeast extract available in particular from ALBAN MÜLLER under the trademark Drieline®; and the palmitoyl pentapeptide marketed by SEDERMA under the trade name Matrixil®; or on the inhibition of serine proteases such as leukocyte elastase or cathepsin G. Mention may be made of: the peptide extract of leguminous seeds (Pisum sativum) sold by the company LSN under the trade name Parelastyl®; heparinoids; and pseudodipeptides such as {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} -acetic acid.

The compositions according to the invention are generally administered topically, orally or parenterally. The preferred route of administration will be the oral route.

By "composition administered or applied topically" is meant the dermocosmetic compositions based on pomegranate extract according to the invention which are preferably intended for the treatment of the skin and may be in the form of ointment, creams, milks, ointments, powders, soaked swabs, solutions, gels, sprays, lotions, or suspensions. They may also be in the form of microspheres or nanospheres or lipid or polymeric vesicles or polymeric patches and hydrogels allowing controlled release but also localized patches. These compositions topically can be in either anhydrous form or in aqueous form according to the dermocosmetic indication.

The topical way makes it possible to deploy all the properties of the assets at the level of a specific site, on the zones to be treated. We can use creams, lotions, etc ...

The administration of the compounds according to the invention can also be carried out orally or parenterally by subcutaneous or intradermal injection.

The oral and parenteral routes, on the other hand, have the advantage of acting in a more global way on the whole skin and in these deep layers. For the parenteral route, preference will be given to administration by systemic patch and intradermal, intraepidermal (micro needle, current, radiofrequency, mesotherapy ...).

The compositions according to the invention may be in any of the galenical forms normally used according to the route of use.

In particular, the composition according to the invention may be a food composition for human consumption.

This may include, in particular, whole nutritional foods, beverages, mineral waters, soups, dietary supplements and substitute foods, nutritional bars, confectionery, milk-based products or fermented milk, yogurt, milk-based powders, enteral nutrition products, children's and / or infants' compositions, cereal-based products or fermented cereal products, ice cream, chocolate, coffee, "culinary" products such as mayonnaise, tomato puree or salad dressings.

According to another subject, the present invention relates to a cosmetic method for treating and / or preventing the relaxation of the skin of a subject, comprising at least one step of topical application to the skin and / or oral administration of an effective amount of at least one pomegranate extract or a composition containing it as defined above, according to the technique of usual use of these compositions, beforehand, simultaneously and / or after a weight loss step said subject or previously, simultaneously and / or after an act of cosmetic surgery.

For example: the topical application can be made by spreading on an area of the body, or even by massage to penetrate, creams, gels, serums, lotions, cleansing milks or after-sun compositions on the skin .

The method according to the invention may comprise a single administration or application. According to another embodiment, the administration or the application is repeated, for example, 2 to 3 times daily over a day or more and generally over an extended period of at least 4 weeks, or even 4 to 15 weeks, with the case one or more periods of interruption.

In a particular embodiment of the invention, the pomegranate extract will be administered orally. In this case, the pomegranate extract will preferably be administered at a daily dose of between 0.5 and 2500 mg / day, more precisely between 5 and 500 mg / day.

The subject will preferably be a woman who has just given birth, more specifically a woman within the year or within six months of delivery, or a subject following a slimming diet.

With regard to the products intended to be applied in particular to the skin, these may be aqueous, hydroalcoholic or oily solutions, dispersions of the type of solutions or dispersions of the lotion or serum type, emulsions of liquid consistency or semi-liquid of the milk type, suspensions or emulsions, cream type, aqueous or anhydrous gel, microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and / or nonionic type. The cosmetic and / or dermatological compositions, more particularly concerned by a topical application, can especially be in the form of aqueous, hydroalcoholic or oily solutions, dispersions of the type of solutions or dispersions of the lotion or serum type, emulsions of 25 ml. liquid or semi-liquid consistency of the milk type, obtained by dispersion of a fatty phase in an aqueous phase (HIE) or vice versa (W / O), or suspensions or emulsions of soft, semi-solid or solid consistency of the cream type , aqueous or anhydrous gel, or microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and / or nonionic type. These compositions are prepared according to the usual methods. These compositions may in particular constitute creams for cleaning, protection, treatment or care for the face, for the hands, for the feet, for large anatomical folds or for the body, (for example, day creams, night creams). , make-up removing creams, foundation creams, anti-sun creams), make-up products such as fluid foundations, make-up removing milks, body care or care milks, after-sun milks, lotions. skin care gels or mousses, such as cleaning or disinfecting lotions, sunscreen lotions, artificial tanning lotions, bath compositions, deodorant compositions containing a bactericidal agent, gels or aftershave lotions, depilatory creams, or insect bite compositions.

The compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.

When the composition of the invention is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The oils, emulsifiers and coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the cosmetics and / or dermatological field. The emulsifier and the coemulsifier may be present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

When the composition of the invention is a solution or an oily gel, the fatty phase may represent more than 90% of the total weight of the composition.

In known manner, the cosmetic and / or dermatological composition of the invention may also contain adjuvants customary in the pharmaceutical and / or dermatological cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants solvents, perfumes, fillers, filters, bactericides, odor absorbers and dyestuffs. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase and / or into the aqueous phase.

Fats which can be used in the invention include mineral oils such as, for example, hydrogenated polyisobutene and liquid petroleum jelly, vegetable oils such as, for example, a liquid fraction of shea butter, sunflower oil and almonds. apricot, animal oils such as perhydrosqualene, synthetic oils including Purcellin oil, isopropyl myristate and ethyl hexyl palmitate, and fluorinated oils such as perfluoropolyethers. It is also possible to use fatty alcohols, fatty acids such as stearic acid and, for example, waxes such as paraffin, carnauba and beeswax. It is also possible to use silicone compounds such as silicone oils and, for example, cyclomethicone and dimethicone, waxes, resins and silicone gums. These compounds can be functionalized or not.

As emulsifiers that can be used in the invention, mention may be made, for example, of glycerol stearate, polysorbate 60, the cetylstearyl alcohol / cetylstearyl alcohol mixture oxyethylenated with 33 moles of ethylene oxide sold under the name Sinnowax AC by the company HENKEL, the mixture of PEG-6 / PEG-32 / glycol stearate sold under the name of Tefose® 63 by Gattefosse, PPG-3 myristyl ether, silicone emulsifiers such as cetyldimethicone copolyol and sorbitan mono- or tristearate, PEG-40 stearate, oxyethylenated sorbitan monostearate (200E).

As solvents that can be used in the invention, mention may be made of lower alcohols, in particular ethanol and isopropanol, and propylene glycol.

As hydrophilic gelling agents, mention may be made of carboxylic polymers such as carbomer, acrylic copolymers such as copolymers of acrylates / alkyl acrylates, polyacrylamides and in particular the polyacrylamide mixture, C13-14-Isoparaffin and Laureth-7 sold under the name Sepigel 305 ° by the company SEPPIC, polysaccharides such as cellulose derivatives such as hydroxyalkylcelluloses and in particular hydroxypropylcellulose and hydroxyethylcellulose, natural gums such as guar, carob and xanthan and clays.

As lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, or else ethylcellulose and polyethylene.

The cosmetic and / or dermatological compositions comprising at least one pomegranate extract, which are more particularly concerned by the invention, may also be used for intradermal injections (mesotherapy treatment) or via new instruments such as electrophoresis, transdermal patches, microneedles, radiofrequency ...

According to the invention, a "physiologically acceptable medium" is a cosmetically or pharmaceutically acceptable medium compatible with the skin, the mucous membranes, the nails and / or the hair.

By "cosmetically acceptable medium" means a medium without unpleasant appearance, and which does not generate tingling, tightness or redness unacceptable to the user.

In the following description and examples, unless otherwise indicated, percentages are percentages by weight and ranges of values in the form "between ... and ..." include the specified lower and upper bounds. The ingredients are mixed, before they are shaped, in the order and under conditions easily determined by those skilled in the art.

The following examples are presented by way of illustration and not limitation of the field of the invention.

Example 1: Demonstration of the claimed effect

1. Material and method 1.1. Biological model

- Fabrics: Episkin TM (J13). - Culture conditions: 37 ° C, 5% CO2.

- Culture medium: Lot differentiation medium No. 09-DIFF-010 (Neosynthesis of total GAGs). 1.2. Tested compounds and references Extract tested Appearance / Stock Solution Dilution Age tested stock concentrations E1 (Draco) 'Powder 10 mg / mi Medium 0.001 mg / mi Extract - Storage in DMSO differentiation pomegranate: + 4 ° C under cover or PBS extract from light whole fruit E2 (Naturex, - Powder 100 mg / ml Medium of 0.005 mg / ml Avignon, - Storage with DMSO differentiation France) _ + 4 ° C under cover or PBS Extract of light pomegranate: whole fruit juice extract 1.3. Preliminary cytotoxicity test - Plates: 96 wells - Cells / well: 10000 NHEK in Keratinocyte-SFM medium - Range of tested concentrations: cf. Table 1 - Number of replicates: 6 - Contact cells / compound: 48 hours - Evaluation parameters: reduction of MTT and microscopic observations under microscope (objective x10)

Transformation of the colorless tetrazolium salt (MTT: 3- (4,5-dimethyl-thiazol-2-yl) -2,5-diphenyl-tetrazolium bromide) into blue formazan crystals, soluble in DMSO, is proportional to the activity succinate dehydrogenase (a mitochondrial enzyme).

As a result, the transformation of MTT into formazan crystals by succinate dehydrogenase is proportional to the number of living cells.

The cells were incubated in the presence of MTT and then dissociated and the formazan crystals were solubilized. The optical density (OD) at 540 nm, representative of the number of living cells, was measured on a plate reader (SoftMax, Molecular Devices). 1.4. Synthesis of glycosaminoglycans on EpiskinTM - Culture and Treatment

On receipt, the Episkin ™ reconstructed epidermis were placed in 24-well plates containing 2 ml of differentiation medium and cultured for 24 hours. After incubation, the epidermis were placed in 12-well plates in differentiation medium containing or not (control) the compounds to be tested or reference and incubated for 72 hours. A DMSO control at 0.50 / 0 was performed in parallel. For measurement of GAG neosynthesis, [3H] -glucosamine for total GAG neosynthesis) was added during the last 24 hours of incubation. All the conditions were realized in n = 3 for the neosynthesis of the GAGs (total) and in n = 1 for the histological control.

Measurement of the incorporation of radioactivity into the GAGs At the end of the treatment, the glycosaminoglycans were extracted separately from the culture media and the epidermis using chaotropic buffer (50 mM Tris / HCl, 4 M guanidine, 5% EDTA). mM, pH 8.0) and then purified by ion exchange chromatography (adsorption of anionic molecules on Q-Sepharose beads and desorption of the low and medium-anionic molecules with a solution of urea 6M + 0.2M NaCl).

The radioactivity incorporated into the molecules remaining on the support (predominantly GAGs) was measured by liquid scintillation. The results were expressed as percent change in synthesis of total GAGs relative to the control.

1.5. Data processing

The raw data has been transferred and processed under Microsoft Excel® software. Intergroup comparisons were performed using the Student's T-test. Formulas used in this report: The percentage of stimulation is calculated according to the following formula: Stimulation value (%) = X 100 - 100 Mean of the control The standard error of the mean (es) represents the difference of the mean of the sample relative to the average of the true population. The esm is calculated by dividing the Sd by the square root of the sample size. The percentage of viability is obtained according to the following formula = (OD Compound OD control) x 100-2. Results 2.1 Preliminary Cytotoxicity Test The results of the MTT viability tests and the observation of the cell mats led to the selection of the concentrations to be tested in the rest of the study. No toxicity to the cells was detected at the tested concentrations (see Figure 1). 2.2. Effects of Compounds on Synthesis of Epidermal GAGs Synthesis of Total GAGs on Episkin ™ [3H] -glucosamine incorporation was measured in GAGs present in culture media (Figure 1). At the basal level, the incorporation of [3H] -glucosamine into the GAGs released into the culture medium was almost

40 negligible compared to that measured in the epidermis (40/0 of the total). DMSO control, tested at 0.5%, tended to stimulate the incorporation of [3 H] -glucosamine into the GAGs of the intra-epidermal fraction (20% of the stimulation) whereas no effect was observed at the time. level of GAGs released in the culture medium.

The extract corresponding to the whole fruit extract E1, tested at 0.001 mg / ml, significantly stimulated the incorporation of [3 H] -glucosamine into the GAGs released in the culture medium (99% stimulation). The extract corresponding to whole fruit juice E2, tested at 0.005 mg / ml, significantly stimulated the incorporation of [3 H] -glucosamine into the GAGs released into the culture medium (208% stimulation).

15 3. Conclusion

Pomegranate extracts E1 and E2, thus tested, have demonstrated their ability to stimulate the neosynthesis of total GAGs released into the culture media (approximately factor 2).

Example 2: Examples of compositions 2.1. single-dose gel composition Active ingredient% weight Pomegranate extract: whole fruit juice extract (Naturex, Avignon, France) Lycopene 10 Lactobacillus johnsonii 10 Excipients Sugar syrup 50 Maltodextrin 17 Xanthan gum 0.8 Sodium benzoate 0.2 Water Qs 100 You can take a dose of 200 to 400 ml a day. 25 .2. Capsule composition mg / capsule Pomegranate extract: whole fruit extract 15 (Draco, Avignon, France) Lactobacillus paracasei 1010 cfu Glycerine 150 Magnesium stearate 0.02 Natural flavor 1 One to three of these capsules can be taken daily. 2.3. Capsule composition

The formulation of Example 2.2 is supplemented with a vitamin complex comprising 60 mg of vitamin C, 100 μg of vitamin E and 6 mg of beta carotene.

2.4. Capsule composition

The formulation of Example 2.2 is supplemented with a vitamin complex comprising 100 mg of vitamin C, 100 μg of vitamin E and 6 mg of lycopene per capsule.

2.5. Capsule composition mg / capsule Vitamin C 60 Pomegranate extract: whole fruit juice 5 (Naturex, Avignon, France) Glycerin 150 Magnesium stearate 0.02 Natural flavor 2 20 One to three of these capsules can be taken daily. 2.6. Capsule composition

The formulation of Example 2.5 is supplemented with a vitamin complex comprising 60 mg of vitamin C, 100 μg of vitamin E and 6 mg of beta carotene.

2.7. Capsule Composition 1610 The formulation of Example 2.5 is supplemented with a vitamin complex comprising 100 mg of vitamin C, 100 μg of vitamin E and 6 mg of lycopene per capsule. 2.8. Composition of lotion for the legs as a spray (% by weight) Pomegranate extract: whole fruit juice 5.00 (Naturex, Avignon, France) Vitamin E 0.05 Isopropanol 40.00 Preservative 0.35 Water qs 100, 00 2.9. Composition of firming cream for body care (% by weight) Pomegranate extract: whole fruit juice (Naturex, 5.00 Avignon, France) Vitamin E 0.05 Isopropanol 40.00 Glycerol stearate 1.00 Cetylstearyl alcohol / cetylstearyl alcohol 3.00 oxyethylenated at 33 mole EO (Sinnowax AO sold by Henkel) Cetyl alcohol 1,00 Dimethicone (DC 200 Fluid sold by Dow Corning 1.00) Vaseline oil 6.00 Isopropyl myristate ( Estol IPM 1514 sold by 3.00 Unichema) Glycerin 20.00 Preservative 0.30 Water qs 100.00 2.10. Gel composition for body care (% by weight) Pomegranate extract: 5.00 whole fruit extract (Draco, Avignon, France) Vitamin E 0.05 Vitamin C 2.50 Isopropanol 40.00 Preservative 0.30 Water qs 100.00 2.11. Composition of patch lotion for body care (% by weight) Pomegranate extract: juice of 5.00 whole fruit (Naturex, Avignon, France) Vitamin E 0.05 Isopropanol 40.00 Preservative 0.30 Water qs 100, 00

Claims (13)

REVENDICATIONS1. Non-therapeutic cosmetic use of an effective amount of at least one pomegranate extract, as a firming agent for the skin of a subject having undergone a weight change or before and / or after an act of cosmetic surgery. 2. Use according to the preceding claim, wherein the effective amount of at least one pomegranate extract is used in a proportion of 0.0001% to 1000/0, relative to the total weight of a composition containing . 3. Use according to any one of the preceding claims, for preventing and / or treating loose skin. 4. Use according to the preceding claim, characterized in that said relaxation is due to a modification and / or a decrease in the level of glycosaminoglycans in the dermis. 20 5. Use according to any one of the preceding claims, for maintaining and / or restoring the biomechanical properties of the skin and / or the elasticity and / or the tonicity and / or the firmness of the skin. 6. Use according to any one of the preceding claims, for reducing the appearance of cellulite and / or the appearance of orange peel and / or for treating stretch marks or preventing their appearance. 7. Use according to any one of the preceding claims, characterized in that said modification of weight is due to a slimming regime or to pregnancy. 8. Use according to any one of claims 1 to 6, characterized in that said act of cosmetic surgery is selected from facelift, liposuction and injection of fillers. 9. Use according to any one of the preceding claims, characterized in that the pomegranate extract is an extract of whole fruit. 10. A cosmetic and / or dermatological composition as claimed in any one of claims 2 to 9 comprising, in a physiologically acceptable medium, an effective amount of at least one grape extract associated with at least one graft stimulating agent. macromolecules of the dermis or preventing their degradation selected from iamin, palmitoyloligopeptide; peptides extracted from plants, auxins and lignans, an extract of Saccharomyces cerevisiae, an extract of alga Macrocystis pyrifera, a product of fermentation of milk by Lactobacillus seen / taken, an extract of brown alga Padina pavonica; Salina zooplankton extract, palmitoyl pentapeptide; a peptide extract of Pisum seeds; heparinoids; and {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} -acetic acid. 11. A non-therapeutic cosmetic method for treating and / or preventing relaxation of the skin of a subject, comprising a step of oral administration or topical application to the skin of an effective amount of at least one extract of pomegranate or a composition containing, previously, simultaneously and / or after a weight loss step of said subject or before and / or after an act of cosmetic surgery. 12. Method according to the preceding claim, characterized in that the pomegranate extract is taken orally at a daily dose between 0.5 and 2500 mg / day. 13. A method according to any one of claims 11 and 12 wherein said subject is a subject in a slimming regime.