FR2867683A1 - COSMETIC OR DERMATOLOGICAL COMPOSITIONS AND THEIR APPLICATIONS - Google Patents

Abstract

The invention relates to the field of the necessities of life and more particularly to the fields of cosmetology, pharmacy and more specifically dermatology. The present invention more particularly relates to a new use of aspartame for the production of cosmetic or pharmaceutical compositions, especially dermatological compositions intended to inhibit lipogenesis. The present invention also relates to novel formulations comprising, as active principle, aspartame and one or more agents promoting lipolysis associated with a suitable cosmetic or dermatological vehicle, preferably a transdermal vector. The present invention also relates to a cosmetic care method for combating adiposity, cellulite, cellulite and / or orange peel, and / or to obtain a slimming effect of the body and / or face. according to the invention relate in particular to the realization of care or topical treatment of the body and / or the face of the man and / or the animal.

Description

COSMETIC OR DERMATOLOGICAL COMPOSITIONS AND THEIR APPLICATIONS

  The invention relates to the field of the necessities of life and more particularly to the fields of cosmetology, pharmacy and more specifically dermatology.

  The present invention more particularly relates to a new use of aspartame for the production of cosmetic or pharmaceutical compositions, especially dermatological compositions for inhibiting lipogenesis. The present invention also relates to novel formulations comprising, as active principle, aspartame and / or one of its derivatives and at least one agent promoting lipolysis, in a suitable cosmetic or dermatological vehicle, preferably a transdermal vector. Advantageously, the agents promoting lipolysis are chosen from inhibitors of phosphodiesterase, activators of adenylate cyclase and / or stimulators of transporters of residues of lipolysis. The subject of the present invention is also a cosmetic care method for combating adiposity, cellulite, cellulite and / or orange peel, and / or obtaining a slimming effect on the body and / or face. The adipocyte is the cell specialized in the storage of energy reserves of the human and animal body. These reserves consist essentially of triglycerides, synthesized from different substrates of food origin (lipids and glucose). The set of synthetic metabolic pathways of the triglycerides of reserve, mainly of the adipose tissue, constitutes lipogenesis. Lipogenesis is strongly related to glucose metabolism. Glucose penetrates into the adipocyte by diffusion facilitated via a glucose transporter, in particular GLUT4, described in numerous publications (Sally Martin et al (2000) Effects of insulin on intracellular GLUT4 vesicles in adipocytes: evidence of a secretory mode Journal of Cell Science 113, 3427-3438.). It then allows the synthesis of glycerol-3-phosphate, then triglycerides. These triglycerides are then degraded by a mechanism of lipolysis within the adipocyte to meet the energy needs of the body. These two reactions of biosynthesis and biodegradation of lipids are controlled by a large number of constitutional and environmental factors including hormonal, dietary, psychological, energy expenditure As long as the two reactions are balanced, the size of the adipocytes and adipose tissue they constitute, remain normal. As a result of excess food, a lack of energy expenditure, or endocrine or metabolic dysfunction for example, it happens that the amount of triglycerides stored by lipogenesis is greater than that degraded by lipolysis. This imbalance results in adiposity, ie an accumulation of triglycerides in the adipocyte that hypertrophies. Adipose tissue develops unsightly in certain parts of the body. Weight gain can also result. In addition, the development of adipocytes in the hypoderm, associated with the deformation of neighboring conjunctive cells and the rigidity of the fibrous network that maintains them, sometimes results in unsightly manifestations, namely an increase in the thickness of the skin and gives it a padded, irregular appearance called orange peel. It's cellulite.

  Cellulite and adiposity are considered very unsightly and thus often experienced as a real complex, especially by women. Adiposity can also lead to pathological conditions such as obesity. Many studies have been conducted in the fields of dermatology and cosmetology to determine molecules that can act in topical application on the metabolic reactions of the adipocyte to reduce its volume.

  Lipolysis is a first course of action that has been widely investigated. The most well-known lipolysis promoters are, in particular, adenosine-3 ', 5'-cyclic monophoshate (cAMP), phosphodiesterase inhibiting agents such as flavones and xanthine bases, theobromine, theophylline and caffeine (FR2624010 Pierre Fabre) Dermo-Cosmetic) or the stimulating agents of adenylate cyclase such as forskolin and the diterpenes of Salvia miltiorrhiza, an extract of Tephrosia purpurea, agents stimulating the secretion of leptin such as phytosphingosine (FR2836630-LVMH Research), agents thermogenic such as oleyl-estrone. The majority of marketed slimming products thus contain active ingredients intended to stimulate the mobilization of triglycerides stored in fat cells.

  Lipogenesis is another particularly interesting way to reduce the amount of triglycerides stored. Thus, some agents inhibiting lipogenesis have been discovered. Leptin secreting agents have been identified, however the effect obtained depends largely on the sensitivity of the receptors of each individual to leptin. Patent WO02 / 066000 (Sederma) describes the use of boldine as a calcium channel agent. WO03 / 006009 (Zenbio, Inc.) discloses the use of a combination of conjugated linoleic acid, imidazole and antifungal agent as an inhibitor of lipogenesis. An alkylated arachidonic acid complex is also described for its inhibitory action on lipogenesis. Rutin is also known as an inhibitor of lipogenesis and this by decreasing the permeability of blood vessels and improving their resistance. WO89 / 11295 (Demeys Pierre et al.) Discloses antagonists (sphingosine and staurosporine) of protein kinase C for obtaining an inhibitory action of lipogenesis. Hydroxycitrate has also been described as an inhibitor of lipogenesis via inhibition of citrate lipase. It is in particular extracted from the plant Garcinia cambodgia (FR2801789 Clarins). Many compounds of the benzodioxin, benzoxazine, benzopyran, benzofuran and oxirane carboxylic type have also been described as lipogenesis inhibiting agents without any further precision as to their route of action (EP0019955, EP0018682 A1, EP0018674 A1, Shell International Research). . The patent FR2795959 (Codif International) also describes fatty acids as an inhibitor of lipogenesis by inhibiting the enzyme responsible for the synthesis of saturated fatty acids. Other inhibitors of lipogenesis act on adrenergic receptors such as idazoxan (FR 2801786 Pierre Fabre). Disglucosyne, a ceramide-like molecule, has also been discovered. This molecule is described, without any more precision, as being opposed to the uptake of glucose by fat cells.

  The regulation of lipogenesis is thus multifactorial and particularly complex. New means of action are always needed to act on each of the metabolic pathways of lipogenesis and to block it at different levels.

  Conducting active research on adipocyte metabolism, the Applicant has found, particularly surprisingly, that aspartame is a new active agent inhibiting lipogenesis.

  The methyl ester of the dipeptide L-aspartyl-L-phenylalanine, whose common name is aspartame (CAS No. 22839-47-0), is widely used in the food industry for its ability to intensify the flavor of certain flavors and as a sweetener intense. Its 200-fold sweetening capacity, superior to that of sucrose, allows it to give a strong sweetness to desserts, drinks and sweets. Aspartame is also present in many drugs for oral administration. This constituent is, moreover, known for its low calorie properties. Indeed, aspartame is degraded during the process of digestion, in the gastrointestinal tract, in its two constituent amino acids and in methanol, which then pass into the blood. Aspartame can therefore confer a sweet perception comparable to that of sugar, without bringing energy directly usable and storable by the body. Always used in oral form, this compound had so far never been used in topical form and thus had previously never been used in the body in its integrity form.

  In addition, the use of aspartame as a slimming agent is particularly remarkable in that it has been shown by the Applicant that aspartame can reduce the transport of glucose in the adipocyte. Without the invention being limited to a specific mode of action, one hypothesis would be that aspartame prevents the membrane transporters of glucose, in particular GLUT 4, from transferring glucose from the extracellular medium to the interior of the adipocytes, where the it would be transformed into triglycerides and stored. According to this hypothesis, aspartame would be able to decoy these glucose transporters and to enter the cell instead of glucose. Low caloric, it would then allow very little neo-lipid synthesis. It appears that aspartame is an inhibitor of lipogenesis, in particular by inhibition of glucose transport. Applied locally, it allows, moreover, to obtain a targeted action, precise, perfectly localized allowing the volume reduction of the adipose tissue, the reduction or the prevention of the cellulite, the cellulite and / or the orange peel effect . The Applicant has, moreover, found, according to another aspect of the invention, that particular combinations with certain slimming agents show a synergistic effect on cellulite.

  A first object of the invention is the use of aspartame for the production of cosmetic or dermatological compositions intended to inhibit lipogenesis.

  The present invention also relates to a new cosmetic or dermatological composition characterized in that it contains, as active ingredient, at least aspartame and a lipolysis stimulating agent, in a suitable cosmetic or dermatological vehicle.

  By aspartame is meant according to the invention, the methyl ester of the dipeptide L-aspartyl-L-phenylalanine. Acyl derivatives of aspartame, preferably with a fatty acid, could also be used, as long as they do not disturb the stability of aspartame and its lipogenesis inhibitory activity.

  The composition preferably contains from 0.01 to 10% of aspartame relative to the total weight of the composition, and advantageously from 0.02 to 0.5% of aspartame.

  The Applicant has found that the combination of aspartame with lipolysis stimulating agents has particularly interesting synergistic effects. The composition according to the invention thus contains one or more of these agents, preferably chosen from the phosphodiesterase inhibiting agents and in particular caffeine, the activating agents for adenylate cyclase and in particular forskolin, and the agents stimulating the carriers of the residues of lipolysis, in particular genistein or another isoflavone of Daidzein type or glycitein glycosylated or not, and mixtures thereof. These agents may be incorporated in pure form or in the form of plant extracts containing it, which are cosmetically compatible.

  Activating agents of adenylate cyclase perform a combination with aspartame particularly interesting. They act directly on an adipocyte enzyme, adenylate cyclase and thus stimulate the production of intracellular cAMP. CAMP is the cosubstrate of a key enzyme in lipolysis, the hormone-sensitive lipase that hydrolyzes triglycerides to fatty acids and glycerol. Among the activators of adenylate cyclase, there may be mentioned forskolin, derivatives of fluorine, an extract of Tephrosia purpurea. Forskolin will preferably be used, advantageously at a concentration of between 0.0005 to 2%, and preferably from 0.001 to 0.01% by total weight of the composition. Preferably, forskolin will be used in the form of a purified extract of a plant containing it, in particular Coleus forskohlii.

  Inhibitors of phosphodiesterase protect the synthesized cAMP and achieve a particularly interesting combination with aspartame and adenylate cyclase activators. Together, they induce overconcentration of cAMP in the cell, which strongly stimulates hormone-sensitive lipase and increases lipolysis.

  By way of example of phosphodiesterase inhibitors, mention may be made of xanthines, such as theobromine, theophylline, aminophylline, caffeine and / or its derivatives, in particular carboxylic derivatives such as those described in patent FR 2,639,541. (Pierre Fabre Cosmetique). It will be used, preferably, caffeine at concentrations ranging from 0.5% to 15% relative to the total weight of the composition, and preferably from 1 to 10%. The caffeine will preferably be used combined with a solubilizing agent such as sodium salicylate, sodium benzoate, ethanol, sodium citrate or ethoxy diglycol. It is preferable to use sodium salicylate, advantageously in a caffeine / sodium salicylate ratio of about 2/1.

  Transporters of lipolysis residues include glycerol transporters, mono- and diglycerides and fatty acid transferases (FATs). The stimulators of these porins have a particularly interesting action. They allow, indeed, to detoxify the cell and thus participate in the activation of lipolysis. As examples of agents stimulating transporters residues of lipolysis, there may be mentioned a phyto-estrogen: genistein or isoflavone-rich extracts such as those of corn, clover, lily or hops. Genistein will preferably be used because it specifically stimulates the aquaporin involved in the transport of glycerol in the adipocyte called aquaglyceroporin AQPap and in particular described in the publication Perfumes Cosmetics News No. 175-February-March 2004. It may be used in the form of plant extract such as soybean extract. It will be used advantageously at a concentration ranging from 0.001% to 1%, and preferably from 0.01% to 0.1% by total weight of the composition.

  In a particularly advantageous manner, the composition according to the invention will contain aspartame and these three types of agents. The four molecules act synergistically on the overall metabolism of adipocytes. Such a combination acts specifically on the dysfunction of the membrane transporter system of adipocytes, in particular GLUT4, FAT and the glycerol transporter. This type of dysfunction is indeed common in cellulite. Such a combination thus allows the complete and specific treatment of cellulite by reducing the volume of the treated areas, the visible improvement of the appearance of orange peel and the reduction of the size and density of the adipocytes, as this is demonstrated in Example I. This complete combination activates lipolysis, decreases lipogenesis, and rebalances lipid metabolism at the level of the adipocyte. The regulation of the transport mechanisms of the cell thus leads to the reduction of adipocytes. This combination is therefore suitable for producing a slimming agent. The activity of a composition containing such a combination was tested on adipocyte metabolism, compared to other pre-existing conventional compositions. This study, presented in Example II, demonstrates the inhibitory effect of aspartame on lipogenesis. Compared to the control, the glucose level, in the culture medium of the adipocytes, remains at a level greater than 28%, after a contact time of 8 days, which reflects a decrease in glucose consumption and therefore the inhibitory effect of aspartame on lipogenesis. The inhibitory effect of lipogenesis is, in addition, significantly higher than that obtained with conventional slimming compositions. This study shows, moreover, that the composition according to the invention acts completely on the metabolism of adipocytes, significantly activating lipolysis (+ 30% under these conditions), and significantly decreasing lipogenesis (-28% glucose). captured) and the size of the adipocytes (surface: -26%, perimeter: - 16%, diameter: -17%).

  The compositions containing aspartame will be made in the usual manner. During formulation, the aspartame is dispersed in an aqueous phase at a temperature below 80 C with stirring. The other constituents are added in the usual manner. Aspartame can also be mixed with one or more types of lipolysis stimulating active ingredients, in particular for the production of a slimming agent, and stored in powder form. During the formulation of the composition, the powdered slimming agent will then be dispersed in the aqueous phase and the rest of the ingredients will be added under the usual conditions. Aspartame is a hydrophilic molecule. Alone or in combination in the compositions, it will preferably be transported to the membrane transporters of the glucose of the adipocytes, which constitute their targets of action, by an appropriate transdermal vector.

  By suitable transdermal vector is meant according to the invention, a carrier, a carrier or a carrier compound that promotes the passage of aspartame applied cutaneously through the skin barrier and adipocytes. By way of example of these vectors, mention may be made of amphiphilic molecules such as surfactants. The vector may in particular be chosen from: sucrose esters such as sucrose stearate, sucrose distearate or sucrose cocoate; glycol esters; glycerol; butylene glycol; propylene glycol; dicapryl glycol; glyceryl caprate, glyceryl caprylate and other glycerol esters. The vector may also be chosen from other types of absorption promoters such as cellulose, hydroxyalkyl cellulose, transcutol, glycerol, lamellar emulsifiers such as Montanov 68 or Arlatone 2121, the combination of steareth-2 and steareth -21 (marketed under the name Brij 72/721). Dispersed systems such as conventional emulsions, triple emulsions, nanoemulsions, so-called PIT (phase inversion) emulsions, gels, cream gels and encapsulated systems such as liposomes, micro- and nanoparticles, microspheres and micelles, vesicles, lipoids, globules, colloidal balls, sponges, cyclodextrins also enhance the penetration of hydrophilic compounds across the skin barrier.

  According to a preferred embodiment, a biomimetic vector will be used, ie composed of molecules having a nature close to the skin. It may be specific membrane lipids such as natural or synthetic phospholipids, in combination or not with other amphiphilic or membrane compounds such as ceramides, phytosterols or glycolipids. To achieve this vector, one can refer for example to the patent WO0045774 (Phares Pharmaceutical Research). According to this patent, sodium salicylate is dispersed first in an aqueous solution, the active ingredients are then added, then the solution is heated to a temperature of about 60 C and the membrane phospholipids are then added. By this vectorization, caffeine, of amphiphilic nature is advantageously associated with the membrane formed by the phospholipids and penetrates to the cells. According to a particularly advantageous embodiment, aspartame and lipolytic agents, in particular genistein, caffeine, and forskolin are also vectorized, preferably by natural phospholipids.

  The transdermal vector may also be a gelling and / or thickening agent sold under the name Heliogel by Lucas Meyer Cosmetics. This agent is formed from a combination of three constituents, namely a copolymer of polyacrylamide and ammonium acrylate and / or anionic acrylic copolymer, lecithins or phospholipids of plant origin, and a polyglyceryl acylate. Said gelling and / or thickening agent will advantageously consist of 28 to 46% of sodium acrylate / acryloyl dimethyl taurate copolymer, 21 to 34% of hydrogenated polylisobutene, 6 to 24% of phospholipids, 4 to 16% of oil. of sunflower, and from 10 to 20% of polyglyceryl stearate.

  Other lipolysis promoting active agents, such as carnitine, may be included in the compositions of the ANP contained in particular in the extracts of sacred lotus (Nelumbo nucifera) or ivy (Hedera helix).

  The compositions may contain other cosmetically or dermatologically acceptable active agents making it possible to fight against the aggravating factors of cellulitis, in particular venous, capillary, lymphatic and hormonal disorders. Thus, the compositions may advantageously contain agents acting on the microcirculation or venous tonics such as ruscogenin, a Gingko biloba extract or a red vine extract, antioxidant and anti-inflammatory agents such as green tea extract or protease bromelain, vasoprotective agents such as extracts of red algae or chestnut, toning agents such as ginseng, soothing agents such as bisabolol, anti-oedematous agents promoting cellulite deleaeration such as extract small holly, alpha hydroxy acids (AHA), vitamins, vegetable proteins and tensors.

  Other agents that can promote lipogenesis, such as garcinol (Garcinia cambodgia fruit bark extract subject to the patent FR2801789), may be included, possibly in combination with a biofiltrate of Candida lipolytica. We can also use an extract of the seaweed Odontella aurita.

  Such compositions may also contain the pharmaceutically or cosmetically acceptable vehicles or diluents, which are usual, and suitable especially as diluent, dispersing agent, gelling agent, solid emollient, gums, resins, solvents, fillers such as modified starches and polymers, titanium dioxide or metal stearate, preservatives, essential oils, pearlescent agents, dyes, odor absorbers, pH-regulating agents or neutralizing agents, thickening agents, promoters absorption, flavoring or perfuming agents, mineral pigments, such as iron oxides, oily agents such as vegetable oils or fats, fats of animal origin (lanolin), synthetic oils (perhydrosqualene), silicone oils (cyclomethicone), fluorinated oils (perfluorinated polyethers, perfluorodecalin), esters, alcohols fatty acids (cetyl alcohol), waxes (carnauba wax, montana wax, ozokerite, Perilla wax), modified clays, bentones, fatty acid metal salts, hydrophobized silica, polyethylenes, mica or other substances used in cosmetics.

  The choice and / or the quantity of the ingredients complementary to the composition will also be determined by the tolerance and the specific needs of the skin on which the composition will be applied as well as by the properties and the desired consistency for the composition according to the invention. The various adjuvants are employed in proportions usually used in the field of cosmetics, for example from 0.01 to 20% of the total weight of the composition.

  The compositions according to the invention are in a form suitable for application to the skin and / or the mucous membranes in humans and / or animals. They are in the form of gel, cream, lotion, emulsion or dispersion, especially oil-in-water or water-in-oil, multiple emulsion, ointment, milk, foam, spray, patch or impregnated fabric. The products will advantageously be delivered in unit dose form, by pump bottle or flexible bottle.

  According to the invention, the composition may further incorporate sun protection agents, moisturizing agents such as jojoba extract, softening agents such as hazelnut oil or avocado oil, opalescent agents. or with a pearlescent or glittery aspect, skin tensing agents such as horsetail extract, heating agents or fresh agents such as ethyl alcohol, or smoothing agents.

  As sun-protection agent, it will be possible to use, for example, known organic and / or inorganic physical filters, such as, for example, micronized particles of metal oxide, especially of titanium, iron and cerium oxides. , aluminum, zinc, particles of metal silicates, organic compounds such as tetramethyl butyl phenol bis-benzotriazolyl (MBBT marketed by Ciba), ethylhexyl methoxycinnamate (Parsol MCX), butyl methoxydibenzoylmethane (Parsol 1789). For the realization of sunscreens, the choice of the filter used according to its physicochemical properties and the choice of its concentration according to the desired final consistency of the composition according to the invention will be determined.

  According to the invention, aspartame or cosmetic or dermatological compositions containing predefined are used to inhibit lipogenesis. They can be used, optionally in combination with other active agents, for the production of cosmetic or dermatological products.

  The subject of the invention is therefore the use in cosmetics of aspartame, preferably in the form of the predefined composition containing a lipolysis stimulating agent, for the care, treatment and / or prevention of cellulitis, the adiposity, its unsightly manifestations, adiposity and / or for the aesthetic improvement of the silhouette, and / or to obtain a slimming effect of the body and / or face and in particular to reduce the volume of adipose tissue.

  By cellulite, we hear, according to common language, aesthetic cellulite. This anomaly of the fatty tissue in its gynoid distribution, very localized is called gynoid lipodystrophy. It is unsightly characterized by a bilateral subcutaneous and symmetrical relief, with padded appearance called orange peel, thick consistency, thickened, sometimes nodular, not very mobile, not very supple, sometimes leading to painful sensitivity to palpation. It has no effect on health and only has an aesthetic disadvantage. Moreover, it is not necessarily associated with being overweight. Thus, the unsightly manifestations of cellulite include the irregular and non-uniform appearance of the skin, cellulite, orange peel.

  The compositions according to the invention are particularly suitable for the production of slimming products, anti-cellulite or anticapiton care, care improving the silhouette, anti-stretch mark treatments by topical application in the cosmetic field.

  The subject of the invention is also the use in dermatology of aspartame, preferably in the form of the predefined composition containing a lipolysis stimulating agent, for producing a topically applied medicament, intended in particular to prevent and / or prevent treat obesity and / or overweight. These compositions are more particularly suitable for the symptomatic treatment of subcutaneous fat overloads.

  The invention further relates to a method of cosmetic care of the body consisting in applying to a skin area concerned, aspartame preferentially in the form of the predefined composition containing a lipolysis stimulating agent, for the care, the treatment and / or prevention of cellulite and its unsightly manifestations, the aesthetic improvement of the silhouette, and / or to obtain the reduction of adipose tissue volume and / or a slimming effect of the body and the face.

  The compositions according to the invention have no toxicity and cause no local intolerance. They are not allergenic either.

  The following examples are presented to illustrate the invention and should in no way be considered as a limit to the scope of the invention. Unless otherwise stated, the concentrations are given as a percentage based on the total weight of the composition.

  Exemplary embodiment of a composition according to the invention: Composition: In the examples below, a slimming powder agent, particularly interesting according to the invention, is constituted by the combination of the following 4 active agents: aspartame, caffeine , genistein and forskolin, in the following proportions: Ingredient INCI in% by weight of the agent aspartame aspartame 0.5 to 5.

  soybean extract Soybean Glycine Soy Germ Extract 0.5 to 5 extract Coleus forskohlii Coleus forskohlii extract 0.01 to 0.2 lecithin lecithin 5 to 15 caffeine Caffein 40 to 70 sodium salicylate sodium salicylate 20 to 35 silica Silica 0.5 This agent is used for production of a composition consisting of the following ingredients: Phase Ingredient INCI (suppliers) in% A - Demineralized water aqua qs 100% Butylene glycol butylene glycol 3.00 - Polyethylene glycol 4 polyethylene glycol 4 2.00 - EDTA EDTA 0.05 - Elestab CPN chlorphenesin ( Serobiological Lab) 0.10 - Polyglyceryl 3-stearate 2.00 - Dimethicone 3.00 Stearyl heptanoate 2.00 - Caryaryl isononanoate 5.00 - paraben esters 0.20 - Vitamin E acetate tocopheryl acetate 0.20 - Heliogel sodium acrylate copolymer, + hydrogenated polyisobutene, + phospholipids, + polyglyceryl 10-stearate, + Helianthus annuus seed oil (Lucas Meyer Cosmetics) 3.00 C - Cyclomethicone and dimethyconol 1.00 D - Water 25.00 Slimming agent according to the invention 8.30 - CI 14 700 Colorant qs - CI 19 140 Colorant qs - Fragrance 0.30 - Procedure: 1) The slimming agent is produced by mixing the various ingredients in powder form.

  2) The agent is dispersed in water at 65 C with stirring to form the phase D. 3) The phases A and B are separately heated to 75 C and mixed together with stirring.

  4) The mixture thus obtained is allowed to cool. At 65 C, phase D is added.

B 30

E

F

  5) The mixture is allowed to cool slowly. At 40 ° C, phase E is added with stirring.

  6) At about 35 C, the fragrance is added and the whole is well homogenized.

  II Comparative study of the activity of a composition according to the invention on the metabolism of the adipocyte: A. Principle: The lipolytic activity of a composition according to the invention is evaluated by assaying lipids released into the medium explant culture of whole human skin, maintained in survival, and for 8 days in contact with several samples applied topically. The lipogenic activity is evaluated by assaying the residual glucose in the culture medium of explants of human skin under the same conditions.

  The overall activity on the metabolism of the adipocyte is also evaluated by image analysis.

  The viability and morphology of the adipocytes are controlled by a histological study.

  B. Procedure: Whole human skin explants are prepared conventionally (plasty P277-AB32) and put into survival in appropriate cell culture medium (eg BEM Bio-EC's Expiants Medium). The explants are divided into five lots of each five explants: a batch constituting a negative control, called Lot T, intended to receive no treatment.

  a batch constituting the positive control 1, called Lot R1, intended to receive a commercial standard finished product containing alcohol and a mixture of plant extracts (extract of Terminalia sericea, extract of Visnaga ver, Phytosphingosine, and extract Plectranthus barbatus).

  a batch constituting the positive control 2, called Lot R2, intended to receive a conventional commercial finished product containing caffeine.

  a batch constituting the excipient control called Lot E. a tested batch called Lot P intended to receive a composition according to the invention, carried out according to the method described in Example I. At Jo, the explants are put into survival in 1.5 ml of culture medium and the products tested are respectively applied according to each batch as follows: - For Lot R1, a quantity of 20 l of product is deposited on a filter paper disc, dried for 5 minutes allowing alcohol evaporation, then applied on the explant. - The lots R2, E and P each receive 4 mg / cm 2 of product distributed to the fingerstall.

  The application of the tested products is renewed on D2, D4, D6 and D8. The culture medium of the explants is taken on D2, D4, D6 and D8, grouped by batch and stored at -20 C for the different assays. On day 8, the 5 explants of each lot are removed and fixed in ordinary Bouin for histological study.

  For the histological study, the fixed adipose tissue explants are dehydrated, paraffin-impregnated, en bloc, cut and stained with Masson trichrome. The control of the cell viability of the explants on day 8 is carried out by a microscopic examination of the cellular morphology of the different skin compartments.

  By image analysis, the average size of the adipocytes (15 fields analyzed with 3 fields per explant) is measured by analysis of images on histological sections of 5 m thickness observed at the objective 20. It is characterized by the surface average fat cell, mean perimeter and equivalent diameter measured using Qwin LEICA image analysis software.

  The free glycerol is assayed in a culture medium by enzymatic method. The lipids are assayed by thin layer chromatography after their extraction from the culture medium and their separation.

  Glucose is assayed directly in the culture medium by enzymatic assay.

  C. Histological study: The histological study of viability shows that, after 8 days of survival, the control and treated explants do not show any significant alteration or cell necrosis.

  D. Action on lipolysis: The results obtained from assaying free glycerol in the culture medium after 8 days are grouped in the following table: Glycerol in mmol / l% increase by Test student compared to the control Lot Average Standard deviation Probability P Control T 1.70 0.09 RI (Alcohol + extracts 2.20 0.08 30 S (0.0000) plants) R2 (Caffeine) 2, 22 0.06 31 S (0.0000) E (Placebo) 1, 90 0.07 12 S (0.0080) P (composition according to 2.20 0.06 S (0.0000) the invention) For the Student's test, the difference is significant at 95% compared to the control if the probability p is less than 0.05.

  Compared to the untreated control T, it is observed that: The positive control RI (Alcohol + Vegetable Extract) causes a significant 30% increase in the release of free glycerol in the culture medium, after 8 days of treatment. The positive control R2 (Caffeine), causes a significant 31% increase in the release of free glycerol in the culture medium, after 8 days of treatment. The excipient (Placebo), causes a significant increase of 12% in the liberation of free glycerol in the culture medium, after 8 days of treatment.

  The composition according to the invention causes a significant 30% increase in the release of free glycerol in the culture medium after 8 days of treatment. Under the operating conditions described above, the multiple composition according to the invention induces a significant increase of 30% in the release of free glycerol resulting from a lipolytic process.

  This activity is similar to that of the two positive references (reference with Alcohol + Vegetable Extract and reference with Caffeine) tested in parallel under the same conditions. This shows the lipolytic activity of a composition according to the invention.

  E. Action on lipogenesis: The results obtained from the glucose assay present in the culture medium are grouped in the following table: Glucose in mmol / L Increase / Test student test (in%) Lot Average Standard deviation Probability P T indicator 6.52 0.63 - - RI (Alcohol + 7 26 0.50 11 NS (0.104) plant extracts) R2 (Caffeine) 7. 16 0.68 10 NS (0.204) E (Placebo) 6.94 0.95 6 NS (0.483) P (composition 8. 36 0.85 28 S (0.009) according to the invention) For the Student's test, the difference is significant at 95% relative to the control if the probability p is less than 0.05. NS therefore means that the difference is not significant; S indicates that it is The statistical analysis by the Student's test, centered on the composition P according to the invention, leads to the following results: Batch Control T RI (Alcohol + plant extracts) R2 (Caffeine) E (Placebo ) Lot S p (0.009) difference S (0.063) S (0.059) S (0.056) P (composition according to the invention) For the Student's test, the difference is 90% significant compared to the control if the probability p is less than 0.1.

  Compared to the untreated control T, it is observed that: The positive control RI (Alcohol + Vegetable Extract) causes a nonsignificant increase of 11% in the glucose level present in the culture medium, after 8 days of treatment. The positive control R2 (Caffeine), causes a non-significant increase of 10% in the glucose level present in the culture medium, after 8 days of treatment.

  The excipient (Placebo) causes a non-significant increase of 6% in the glucose level present in the culture medium after 8 days of treatment.

  The composition according to the invention causes a significant increase of 28% in the glucose level present in the culture medium, after 8 days of treatment.

  These results show that a composition according to the invention containing aspartame decreases glucose consumption by fat cells and therefore lipogenesis. This inhibition of lipogenesis is significantly higher at 90%, after 8 days of treatment, than the other compositions, devoid of aspartame.

  F. Analysis of images 1. Average surface area of adipocytes: This is the area of the adipocyte reported in m2 as a function of the micrometric calibration of the objective used.

  Number Mean Surface of Adipocyte / Student Test Increase (in%) measured adipocytes (in m2) Lot Mean Standard Deviation Probability P T Indicator 1979 523.7 71.3 - - RI (Alcohol + 2241 442.9 72.1 -15 S (0.006) plant extracts ) R2 (Caffeine) 2345 409.6 69.6 -22 S (0.000) E (Placebo) 2132 461.9 94.3 -12 NS (0.061) P (composition 2444 388.7 90.4 -26 S (0.000) according to the invention) For the Student's test, the difference is 95% significant compared to the control if the probability p is less than 0.05.

  Compared to the untreated control T, it is observed that: the positive control RI (Alcohol + Vegetable Extract) causes a significant decrease of 15% in the average surface area of the adipocytes, after 8 days of treatment.

  The positive control R2 (Caffeine) causes a significant reduction of 22% in the mean surface area of the adipocytes after 8 days of treatment.

  - The Excipient (Placebo), causes a nonsignificant decrease (95% significance) of 12% of the average surface of the adipocytes, after 8 days of treatment.

  -The composition according to the invention causes a significant decrease of 26% of the average surface area of the adipocytes, after 8 days of treatment.

  2. Average perimeter of the adipocytes: This is the total length of the adipocyte limits reported in m as a function of the micrometric calibration of the objective used.

  Average perimeter of the Adipocytes / Control Fat Test Student Increase (in%) measured adipocytes (in m) Lot Mean _ Standard Deviation Probability P T Indicator 1979 97.2 6.9 - - RI (Alcohol + 2241 87.4 6.6 -10 S (0.001) extracts plants) R2 (Caffeine) 2345 84.7 8.1 -13 S (0.000) E (Placebo) 2132 89.1 8.4 -8 S (0.009) P (composition 2444 81.4 9.5 -16 S (0.000) according to the invention) For the Student test the difference is 95% significant relative to the control if the probability p is less than 0.05.

  Compared to the untreated control T, it is observed that: the positive control RI (Alcohol + Vegetable Extract) causes a significant decrease of 10% in the mean perimeter of the adipocytes, after 8 days of treatment.

  The positive control R2 (Caffeine) causes a significant 13% decrease in the average perimeter of the adipocytes, after 8 days of treatment.

  -The Excipient (Placebo), causes a significant decrease of 8% of the average perimeter of the adipocytes, after 8 days of treatment.

  - The composition according to the invention causes a significant decrease of 16% of the average perimeter of adipocytes after 8 days of treatment.

  3. Average equivalent diameter of the adipocytes This is the equivalent diameter of the circle which has the same surface as the adipocyte, reported in m according to the micrometer calibration of the objective Number Average diameter of the Student Test Increase of adipocytes / Control (in%) measured adipocytes (in m) Lot Mean Standard deviation Probability P T-control 1979 23.9 1.6 - - R (Alcohol + 2241 21.9 1.9 -8 0.005 plant extracts) R2 (Caffeine) 2345 20.7 2.0 -14 0.000 E (Placebo ) 2132 22.0 2.5 -8 0.024 P (composition 2444 19.8 2.6 -17 0.000 according to the invention) For the Student's test, the difference is significant at 95% relative to the control if the probability p is less than 0.05.

  Compared with the untreated control T, it is observed that: The positive control RI (Alcohol + Vegetable Extract) causes a significant decrease of 8% in the average equivalent diameter of the adipocytes, after 8 days of treatment.

  The positive control R2 (Caffeine), causes a significant decrease of 14% of the average equivalent diameter of the adipocytes, after 8 days of treatment.

  The Excipient (Placebo) causes a significant decrease of 8% of the average equivalent diameter of the adipocytes after 8 days of treatment.

  The composition according to the invention causes a significant decrease of 17% in the average equivalent diameter of the adipocytes after 8 days of treatment.

  Phase Ingredient INCI (Suppliers) in% A - Demineralised water aqua qs 100% - Butylene glycol butylene glycol 3.00 - Glycerin glycerin (Interchemistry) 2.00 EDTA EDTA 0.05 - Elestab CPN - Heliogel chlorphenesin (Lab Serobiological) 0.20 sodium acrylates copolymer, + hydrogenated polyisobutene, + phospholipid, + polyglyceryl 10-stearate, + Helianthus annuus seed oil (Lucas Meyer Cosmetics) 3.00 III Other examples of compositions E Slimming sprays with alcohol: - Composition in percent: 20 B - Demineralized water aqua 25.00 - Slimming agent according to 8.30 C - Heliogel sodium acrylate copolymer, 2.00 + hydrogenated polyisobutene, + phospholipids, + polyglyceryl 10-stearate, + Helianthus annuus seed oil (Lucas Meyer Cosmetics) D-Alcohol alcohol 20.00 E-Dimethicone dimethicone polymer Crosspolymer 5.00 - Fashion Procedure: 1. The phases A and B are heated separately at 70-75 C with stirring until they are each well homogeneous.

  2. Phase B is slowly introduced into phase A with slow stirring.

  3. Phase C is added with gentle stirring.

  4. The mixture is allowed to cool.

  5. When the temperature is lower than 30 C, the phases D and E are added.

  Non-alcoholic slimming spray: INCI (Suppliers) in% aqua qs 100% butylene glycol 3.00 glycerin (Interchimie) 2.00 EDTA 0.05 Chlorphenesin (Lab Serobiological) 0.20 sodium acrylate copolymer, + hydrogenated polyisobutene, + phospholipids, + polyglyceryl 10-stearate, 0.50 polyglyceryl 3 stearate 2.00 glyceryl stearate citrate 2.00 cetearyl ethyl hexanoate 3.00 pentaerythrityl tetraethylhexanoate 4.00 5.00 0.20 0.30 25.00 6.50 10 Percent composition: Phase Ingredient A - Deionized water Butylene glycol - Glycerin

- EDTA

- Elestab CPN - Heliogel C 45 D

B

  cyclomethicone esters of paraben tocopheryl acetate - Water aqua - Slimming agent according to the invention - Laminactin Glycerin + aqua + lysolecithin + Perilla fr utescens seed oil (Lucas Meyer Cosmetics) 2.00 E - Fragrance fragrance 0.20 - Polyglyceryl stearate -3 - Citrate stearate Glyceryl - Ethyl cetearyl hexanoate - Pentaerythrityl tetraethylhexanoate - Cyclomethicone - Paraben esters - Vitamin E acetate - Procedure: 1. Phases A, B are heated separately at about 75-80 C with stirring until they are each homogeneous.

  2. Phase B is introduced into phase A with stirring and homogenization (Silverson stirrer, Ultra Thurax for 2 minutes).

  3. Phase C, heated to 70-75 ° C., is slowly added to the mixture with gentle stirring until completely homogenized.

  4. The whole is allowed to cool with slow stirring.

  5. When the temperature is below 35 C, the phases D and E are added.

  Thinning cream: - Percent composition: INCI (Suppliers) in% aqua qs 100% Phase Ingredient A - Demineralised water - Butylene glycol butylen glycol 3.00 - Glycerin glycerin (Interchemistry) 2.00 - EDTA EDTA 0.05 - Elestab CPN chlorphenesin (Lab Serobiology ) 0.20 - Biophilic C12-16 alcohols, + hydrogenated 2.00 + palmitic acid (Lucas Meyer Cosmetics) - Hydroxyethyl cellulose hydroxyethyl cellulose 0.50 B Amisol Soft behenic alcohol, + glyceryl stearate, 2.00 + phospholipids + glycine soy sterols (Lucas Meyer Cosmetics) - ester with emollient function 4.00 - polydecene polydecene 5.00 - grape seed extract Vitis vinifera 2.00 - dimethicone 5.00 - cetiol SB45 Butyrospermum parkii (Cognis) 1.00 - vitamin E acetate tocopheryl acetate 0.50 - paraben esters paraben esters 0.20 C - aqua water 25.00 - Agent slimming machine according to the invention 8.30 D - Mamaku VE aqua + cyatheaceae extract (Lucas Meyer Cosmetics) 2.00 E - Heliogel sodium acrylate copolymer, + hydrogenated polyisobutene, + phospholipids, + polyglyceryl 10-stearate, + Helianthus annuus seed oil 2.00 (Lucas Meyer Cosmetics) F -Fragrance fragrance 0.20 Procedure: 1 Phase A is heated separately to about 70-75 C with gentle shaking and maintained for at least 20 minutes to obtain good hydration.

  2. Phase B, heated to 70-75 C is slowly introduced into phase A with slow stirring and maintained for about 20 minutes 3. The stirring speed is increased (Silverson Ultra Thurax 3000rpm stirrer, 3min) during a so-called phase emulsification.

  4. Phase C heated to 70-75 C and homogeneous is added to the mixture.

  5. The whole is allowed to cool.

  6. When the temperature is below 40 C, phase D is added.

  7. Phase E and then phase F are added and stirring is maintained until a homogeneous product is obtained.

  É Slimming serum: - Percent composition: INCI (Suppliers) in% Phase Ingredient A - Demineralized water aqua qs 100% - Butylene glycol butylene glycol 3.00 - Glycerin glycerin (Interchemistry) 2.00 - EDTA EDTA 0.05 - Elestab CPN Chlorphenesin (Lab Serobiology ) 0.20 - Biophilic C12-16 alcohols, Satiaxane CX91 cyclomethicone silicone - isodecyl neopentanoate - esters of paraben vitamin E acetate Water Slimming agent according to - Heliogel E - Laminactin F - Fragrance 20

B

C D

  + hydrogenated + palmitic acid (Lucas Meyer Cosmetics) 2.00 xanthan gum 0.30 3.00 3.00 4.00 0.20 0.20 25.00 the invention 8.30 sodium acrylates copolymer, + hydrogenated polyisobutene, + phospholipids, + polyglyceryl 10-stearate, + Helianthus annuus seed oil (Lucas Meyer Cosmetics ) 1.00 Glycerin + aqua + lysolecithin + Perillarutescens seed oil (Lucas Meyer Cosmetics) 2.00 fragrance 0.30 paraben esters tocopheryl acetate - Procedure: 1. Phase A is heated separately to about 70-75 C with gentle shaking and maintained for at least 20 minutes. minutes to obtain good hydration.

  2. Phase B, heated to 70-75 ° C is slowly introduced into phase A with slow stirring and maintained for about 5 minutes 3. The stirring speed is increased (Silverson Ultra Thurax stirrer 3000 rpm, 3 min) to proceed an emulsification phase.

  4. Phase C heated to 70-75 C and homogeneous is added to the mixture.

  5. Phase D is added to the mixture with gentle stirring and stirring is maintained until a homogeneous assembly is obtained.

  6. The whole is allowed to cool.

  7. When the temperature is below 35 C, the phases E and F are added.

  É Slimming gel with alcohol: - Composition in percentage: Phase Ingredient A - Demineralized water - Butylene glycol - Glycerine

- EDTA

  - Elestab CPN - Heliogel - Procedure: 1. Phase A is heated to 70-75C.

  2. Phase B is prepared with hot water and kept under slow stirring until a smooth and homogeneous phase is obtained (approximately 20 minutes) 3. Phase B is added to phase A with slow stirring.

  4. Phase C is added and the assembly is allowed to cool.

  5. Phase D is slowly added with gentle stirring.

  6. The phases E and F are likewise added. Handsome

  Slimming agent according to the invention C - Heliogel sodium acrylate copolymer, + hydrogenated polyisobutene, + phospholipids, + polyglyceryl 10-stearate, + Helianthus annuus seed oil (Lucas Meyer Cosmetics) 2.00 D-alcohol alcohol 20.00 E-Silicone 5.00 F - CI 14700 dye qs - CI 19140 dye qs 1NCI (Suppliers) in% aqua qs 100% butylene glycol 3.00 (Interchemistry) 2.00 EDTA 0.05 chlorphenesin (Lab Serobiological) 0.20 sodium acrylates copolymer, + hydrogenated polyisobutene, + phospholipids, + polyglyceryl 10-stearate , + Helianthus annuus seed oil (Lucas Meyer Cosmetics) 3.00 25.00 10.00

Claims (17)

CLAIMS:   1. Cosmetic or dermatological composition containing, as active principle, aspartame and at least one lipolysis-promoting agent, combined with a cosmetic or dermatological vehicle.   2. Cosmetic or dermatological composition according to claim 1, wherein the lipolysis promoting agent is chosen from phosphodiesterase inhibiting agents, adenylate cyclase activating agents, lipolysis residues transporters and their promoters. mixtures.   3. Cosmetic or dermatological composition according to claim 1 or 2, wherein the aspartame is present at a concentration of 0.01 to 10% relative to the total weight of the composition.   4. Cosmetic or detachable composition according to one of the preceding claims, wherein the activating agent of adenylate cyclase is forskolin.   Cosmetic or dermatological composition according to Claim 4, in which the forskolin is present in a concentration of between 0.0005 and 2% by total weight of the composition.   6. Cosmetic or dermatological composition according to one of claims 1 to 5, wherein the phosphodiesterase inhibiting agent is caffeine.   Cosmetic or dermatological composition according to claim 6, wherein the caffeine is present at a concentration of 0.5 to 15% by total weight of the composition.   8. Cosmetic or dermatological composition according to one of claims 6 or 7, wherein the caffeine is associated with a solubilizing agent, including sodium salicylate.   9. Cosmetic or dermatological composition according to one of claims 1 to 8, wherein the agent for stimulating transporters residues of lipolysis is genistein.   10. Cosmetic or dermatological composition according to claim 9, wherein the genistein is present at a concentration of between 0.001 to 1% by total weight of the composition.   11. Cosmetic or dermatological composition according to one of the preceding claims, wherein the aspartame is carried by a suitable transdermal vector.   12. Cosmetic or dermatological composition according to claim 11, in which the transdermal vector consists of natural phospholipids.   13. Dermatological composition according to one of claims 1 to 12, for producing a topically applied medicament.   14. Cosmetic use of aspartame or a cosmetic composition containing it according to one of claims 1 to 12 for inhibiting lipogenesis.   15. Cosmetic use of a composition according to one of claims 1 to 12, for the care and / or treatment and / or prevention of cellulitis and / or adiposity and / or its unsightly manifestations, l. aesthetic improvement of the silhouette, and / or to obtain a slimming effect of the body and / or face and in particular the reduction of the volume of adipose tissue.   16. Dermatological use of aspartame or a dermatological composition containing it according to one of claims 1 to 13, for producing a medicament for inhibiting lipogenesis.   17. Dermatological use of a composition according to one of claims 1 to 13 for producing a medicament for preventing and / or treating, by topical application, obesity and / or overweight.