FR2964321A1 - Use of Xylopia aethiopica, as an antagonist of alpha 2-adrenergic receptors in adipose, alone or in combination with at least one other alpha-2-blocker for the preparation of a slimming composition and cosmetic composition - Google Patents

Abstract

Use of Xylopia aethiopica(I), as an antagonist of alpha 2-adrenergic receptors in adipose, alone or in combination with at least one other alpha-2-blocker for the preparation of a slimming composition for topical application, is claimed. ACTIVITY : Anorectic. MECHANISM OF ACTION : Alpha 2-adrenergic receptor antagonist; Alpha-2-blocker.

Description

The subject of the present invention is the use of Xylopia aethiopica as an adipocyte alpha-2 adrenergic receptor antagonist (alpha-2A receptors), or in combination with at least one other alpha-2-blocker in the preparation of a slimming composition for topical application or in the preparation of a composition for massage of the male body and such compositions. It is known that the swelling of the subcutaneous connective tissue called cellulite gives the skin a "padded" appearance. Cellulite is constituted by the local accumulation of fat and water trapped in a gangue with more or less tight compartments. The topical application of an anti-cellulite agent is able to stop the local accumulation of fat by a lipolytic action and thus improve the aesthetic appearance of the skin. Among the methods for stimulating lipolysis, the best known and most widely used is that of inhibiting phosphodiesterase in order to prevent or at least limit the degradation rate of cyclic VAMP. In fact, phosphodiesterase destroys cyclic AMP by transforming it into 5'-AMP so that it can not play the role of activator of lipases responsible for lipolysis. Inhibition of the action of phosphodiesterase thus increases the level of cyclic AMP at the level of the adipocytes, which stimulates the lipolytic activity. Among the various inhibitors of phosphodiesterase and lipases which have been recommended as slimming, one can in particular mention the xanthine bases and more particularly the caffeine. However, in some cases the lipolysis of adipocytes can not be stimulated because these cells responsible for putting the fat in reserve are in addition controlled by alpha-2 adrenergic receptors called alpha-2A, which strongly blocks lipolysis even when this is directly stimulated as with xanthine bases. The blocking of these alpha-2A receptors on the surface of the adipocytes by so-called alpha-2-blocking products is an effective means of solving the problem inherent in blocking these reserves of localized fats resistant to all other cosmetic treatments and even to the diets. or sport. The adipocyte alpha-2 adrenergic receptors (alpha-2A) are normally stimulated, which is called the agonist effect, by the body's natural products (catecholamines including epinephrine) in order to increase the lipid content of these cells, for example by period of 40 diets or stress. By blocking this action, which is called the antagonistic effect, alpha-2-blockers prevent the accumulation of 2 2964321

fat in the adipose tissue and at the same time promote the release of fat. Known alpha-2 blockers (eg, yohimbine) have heretofore been used orally for a variety of purposes including treating obesity. On the other hand, GREENWAY et al. (Clinical Therapeutics, 1987, vol 9 no. 6, p.663-669) have shown that yohimbine-based creams, applied to women otherwise subject to severe caloric restriction and exercise, have an effect indirect lipolytic. But yohimbine, which is classified as a drug, and alpha-2-blockers of this type penetrate poorly (GREENWAY et al. Are forced to use hot wraps) and more unacceptable, they have side effects that prohibit their use. in cosmetics. Xylopia aethiopica (Dunal), or Pepper of Guinea, family Annonaceae 15, is used in food as candy or in hot drinks (coffee Touba.It is also known for its antitussive effects, anti-oxidants (Acta Biologica Hungarica 61 (3), pp.250-261 2010), anti-glaucoma (Igwe, SA, Afonne, JC and Ghasi, SI (2003): Ocular dynamics of systemic aqueous extractsof xylopia aethiopica (African guinea pepper) seeds on visually active volunteers J.Ethnopharmacol., 88 (2-3): 139-42), anti-platelet aggregation (Diderot, NT et al (2005) Prolyl endopeptidase and thrombin inhibitory diterpenoids from the bark of Xylopia aethiopica Biosci Biotechnol Biochem 69, 1763-1766) and even as anti-cancer drugs (Oluwatosin Adaramoye et al., MECHANISM OF ANTIPROLIFERATIVE ACTION OF XYLOPIA AETHIOPICA (ANNONACEAE) DRIED FRUITS EXTRACT ON HUMAN CERVICAL CANCER CELLS.Journal compilation 2010 Nordic Pharmacological Society. & Clinical Pharmacology Toxi cology, 107 (Suppl. 1), 162-692). It is further described as antimicrobial and antifungal (Boakye-Yiadom, K., et al., 1977, Antimicrobial properties of West African medicinal plants.) Antifungal activity of xylopic acid and other constituents of the fruit of Xylopia aethlopica (Annonaceae). Lloydia 40, 543-545). It is precisely by studying the antimicrobial properties of this plant that the Applicant has discovered, quite unexpectedly, that Xylopia aethiopica has a potent alpha-2-blocking action, an adipocyte alpha-2 adrenergic receptor antagonist (alpha-2A). allowing itself to have a slimming effect during topical application. Its use also makes it possible to dispense with the use of preservatives in good numbers of cosmetic compositions. 3 2964321

It was also discovered by chance that when Xylopia aethiopica was applied to massage in the stressed man his libido was improved. Indeed, the high efficacy of Xylopia aethiopica capable of blocking more than 90% of alpha-2A receptor agonist binding by more than 90% allows it to be used alone to fight against localized fatty overloads accessible to cosmetics but also in combination with other alpha-2 jokers and / or other lipolytic agents acting on adipocyte lipases such as xanthine bases. Among the products having this alpha-2-blocking action, mention may be made in particular of Ginkgo biloba, Chrysantellum indicum and Chrysantellum americanum, ivy, Hibiscus and escin. Guinea pepper (Xylopia aethiopica) has never been described as having lipolytic activity. JP 2001064145 recommends it among many other plants to treat the hypofunction of the skin, hair and mouth. The patent 0A8752 (A) would like to disclose its antitussive effects known since the dawn of time in West Africa! Patent KR 20070092127 recommends it among many other plants for its effects of inhibition of methioninase to avoid certain bad smells. Ivy has been used in combination with extracts of meadowsweet, Centella asiatica and laminaria (French Patent No. 2,571,616), in association with a hormone (French Patent No. 2,571,616) or in combination with arnica extract and kola nut extract (French Patent No. 2,499,405) or with a purine base and birch (French Patent No. 2,554,344) or in combination with a substance with action rubefiante (French Patent No. 2,573,306). Escin is usually used as a vasoactive compound in slimming compositions, in particular in association with mucopolysaccharides, the slimming activity of which it strengthens and accelerates without acting directly on the adipocyte, while protecting the blood vessels (French Pat. No. 2,463,617, Belgian Patent No. 888,136, French Patent No. 2,400,902 and French Patent No. 2,356,427). Gingko biloba and Chrysantellum indicum and americanum are described as alpha-2 receptor antagonists, although it is not clear whether this is the alpha-2A type present in adipocytes in overweight areas (see, for example, The invention therefore relates to the use of Xylopia aethiopica as an adipocyte alpha-2 adrenergic receptor antagonist, alone or in combination with at least one other alpha-2-blocker in the preparation of a slimming composition for topical application. It also relates to the use of Xylopia aethiopica alone or in combination with one or more other alpha-2 blockers in the preparation of a composition for the massage of the male body. In addition, these compositions may advantageously be free from the presence of preservative, especially since the areas to be treated may concern the entire body and therefore surfaces that may be important. By use of the expression Xylopia aethiopica is meant the 10 extracts of the plant of the same name. According to the invention, the extracts obtained by zeodration, after roasting or not, are preferably used according to the description given in example 1. By use of the expression "escine" is meant the triterpene saponins of horse chestnut as well as Its use of the expression "ivy" means the extracts of Hedera helix L. (or climbing ivy) containing saponins. These extracts may be prepared by any method for removing constituents such as proteins, lipids, carbohydrates, mucilages and tannins. The combination according to the invention also makes it possible to protect against the negative effect of stress on local overweight. This is because stress causes a discharge of epinephrine (a natural catecholamine) with fattening effects. In particular, this concerns the femoral level of the woman's body, that is to say the "saddlebags" (P. MAURIEGE et al., European Journal of Clinical Investigation (1987) vol 17, p.156 to 165). Thanks to the combination according to the invention, substances released by the human body during stress and which, without it, will strongly inhibit lipolysis at the level of the femoral zone, will have the opposite effect, ie that is to say, to empty the adipocytes of their fat reserve. Furthermore, in these areas, the combination according to the invention has more slimming effect than the most drastic calorie diet because alpha-2A receptors are intended to avoid in these regime conditions, mobilizations of fats fat. The combination of a diet of this type with a topical application of the combination of alpha-2-blockers according to the invention is still recommended and synergistic, because the diet alone does not diminish the saddlebags. A cream containing non-alpha-2-blocking lipolytic actives has very little effect in this area. On the other hand, a cream containing lipolytic active agents including alpha-2-blockers has effects. Nevertheless, these effects are markedly enhanced when the diet is combined with the topical application of a composition based on alpha-2 jokers because the fatty acids released by the composition are used as a source of energy for the body. The same synergistic relationship exists between sport and the topical application of an alpha-2-blocker cream.

The same goes for the man in whom the stress reduces the libido. A massage with a cosmetic composition containing an alpha-2 blocker as described in the present invention makes it possible to reduce the effect of stress and to improve the male libido. The cosmetic composition according to the invention can be produced in various forms, in particular in the form of an oil-in-water (O / W) or water-in-oil (W / O) emulsion, a multiple emulsion (O / W) emulsion. H, E / H / E), microemulsion, twin-phase emulsion, PIT emulsion, nanoemulsion, pseudoemulsion (stable dispersion of two immiscible phases by means of gelling agent), aqueous gel, fatty gel, hydroalcoholic gel, fatty phase, suspension, liquid or solid soap, foaming solution or not, freeze-dried gel or emulsion and / or one of the preceding forms containing microcapsules, nanocapsules , liposomes, ethosomes. Compact or non-makeup type powders may also be made. The cosmetic composition according to the invention may be in the form of creams, liquids, pastes, lotions, emulsions, lotions, oils, gels, solid powders, masks, sticks, sprays. , aerosol.

The cosmetic composition according to the invention may be present, in order to improve the state of the skin more generally, in the form of a formula that can be used orally, such as, for example, capsules, tablets, syrups and even cocktails. The cosmetic slimming compositions according to the invention can also be administered by iontophoresis. Two methods of making Xylopia aethiopica extract are now given by way of illustration. EXAMPLE 1 The single fruit of Xylopia aethiopica or Pepper of Guinea, consisting of numerous carpels arranged in capitulum, is first dried. It is then roasted like coffee beans or it can be used without roasting. Then it is ground to obtain a powder. The solvent, pure water, various aqueous solutions, alcohol or a mixture of two of these solvents can then be added directly. After stirring the liquid is separated by centrifugation or simple filtration. This liquid is then freeze-dried or atomized or dehydrated 6 2964321

by any means respecting its composition such as zeodration using zeolite as a dehydrating agent. The powder thus obtained by each of the processes will be called the native extract of Xylopia aethiopica. This native extract can then be solubilized again in a solvent that can be used in cosmetics, such as water, water and alcohol mixtures, glycerin or butylene glycol. EXAMPLE 2 Description of the efficacy test which revealed the high antagonist power on the adipocyte alpha-2 adrenergic receptors of the extracts produced according to Example 1 This is a test for measuring the antagonistic effect of a human alpha-2A adrenergic receptor extract according to the model described in G. Pharmacol. Exp. Ther., 31: 739-748 in 2006 by BAVADEKAR S.A., et al. "Tetheredyohimbine analogs as selective hum = alpha2a-adrenergic receptor ligands". Evaluation of the expressed human alpha-2A receptor antagonist activity in Xylopia aethiopica CHO cells is performed by measuring its agonist-induced impedance modulating effect using the CellKey Detection Method (CDS). Cells are seeded on 96-well plates at the density of 60,000 cells / well in HESS buffer (Invitrogen) + 20 mM HEPES (Invitrogen) with 0.1% BSA followed by a 60 minute rest period at 28 ° C. before the beginning of the experiment. The plates are placed in the oven and the measurements are made at a temperature of 28 ° C. HBSS buffer (basal level and positive control), reference containing a reference antagonist (determination of IC50 or test compounds are preincubated for 15 minutes before addition of HBSS (basal level) or epinephrine at 10 nM (EC80) as reference agonist Impedance measurements are performed every 10 minutes Standard reference gonator is RX 821002, which is evaluated in each experiment at several concentrations to obtain a dose-response curve. allowing the calculation of IC 50. An extract made with 100% water (PDG-water) and an extract made with 60% ethanol (PDG-alcohol) were evaluated in duplicate. 100% agonist response and by comparison the lower the response of the agonist will be in the presence of the tested extract, the more the latter will have antagonistic effects 40 For the PDP-alcohol extract tested at 3%, we get 9% and 8% in duplicate of 8.5%, which means that the epinephine used as a reference agonist only produces 8.5% of its 7 2964321

effect when the alcoholic extract of Xylopia aethiopica blocks alpha-2A receptors is a specific inhibition of 91.5% For the extract PDG-water tested at 3%, we obtain 6% and 4% in duplicate is an average of 5, 1% which means that the epinephrine used as reference agonist only produces 5.1% of its effect when the aqueous extract of Xylopia aethiopica blocks the alpha-2A receptors is a specific inhibition of 94.9%. These results show, on the one hand, the significant and specifically antagonistic efficacy of the adipocyte alpha-2 adrenergic receptors of Xylopia aethiopica and that this activity does not depend on the type of extraction tested. EXAMPLE 3 Slimming IVE Emulsion Volatile Silicone Oil 10.0 g Perhydrosqualene 18.0 g Vaseline oil 5.0 g Liquid Lanoline 4.0 g Arlacel 165.-. 6.0 g Tween 60 2.0 g Cetyl alcohol 1.2 g 20 stearic acid 2.5 g Triethanolamine 0.1 g Caffeine 1.0 g Aqueous extract of Xylopia aethiopica 3.0 g Propylene glycol 5.0 g 25 Escine 0.5 g Sodium hydroxide 0.008 g Demineralized water 100.0 g Example 4: Several other examples of compositions according to the invention will now be given by way of illustration and without any restriction. According to a first embodiment of the invention the composition is composed of: Acrylate C10-30 0.50 g Ethoxydiglycol 5.00 g Alcohol 2.00 g Butylene glycol 0.24 g Carbomer 0.126 g = TA 0.005 g Macademia oil 0.5 g Hydrogenated lecithin 0.09 g Cyclomethicone 0.20 g TEA99% 0.62 g Hydroalcoholic extract of Xylopia aethiopica_0.5 Caffeine 1.00 Demineralized water qs 100.00

According to a second embodiment, the slimming cosmetic composition may be composed of: Carboxypolymethylene or carboxilic polymer 0.40 g Diethanolamine cetyl phosphate_ 1.50 g Octyl dodecanol 5.50 g Cetyl alcohol 1.00 g Mineral oil 2.00 g Stearic acid 1.00 g Ethoxylated steryl alcohol (20E) 0.30 g Ketostearyl alcohol _______ 1.80 g Macadamia oil __________ 0.50 g

Cyclomethicone ................................. ........... 12.00 g Dimethicone copolyol 3.00 g Phenyltrimetone 2.00 g Glycolic extract of Xylopia aethiopica 3.00 g Sepigel 1.00 g Butylene glycol _6.00 g Mica and titanium oxide 1.00 g Demineralized water q .. .... 100.00 g Four further exemplary embodiments are also set forth below: 1.) Slimming O / W emulsion: - liquid paraffin 6.0 g - liquid lanolin 3.0 g 30 - Arlacel 165 (marketed by Atlas) g Tween 60 (commercially available from Atlas) 2.0 g - cetyl alcohol 1.2 g - stearic acid 2.5 g - retinyl palmitate 0.5 g - volatile silicone oil 10/0 g - triethanolamine 0.1 g - extract aqueous solution of Xylopia aethiopica 2.5 g - Aqueous extract of ivy - 0.5 g - Demineralized water qs 100.0 g 40 2.) Liposome slimming cream: - Cetyl alcohol 4.0 g - B-sitosterol 4.0 gggg - Diketyl phosphate 0.5 g - Carbopol 981 (marketed by Goodrich) 0.2 g - Triethanolamine 0.2 g - Phospholipid 0.05 g - Ginkgo biloba extract 0.1 g - Glycerine extract Hibiscus calyx white g - Aqueous extract of Xylopia aethiopica 1.0 g - Demineralised water qs 100.00g 3.) Slimming emulsion E / H 10 - Protégin (marketed by Goldàchmidt) 19 g - Glycerin 3 Vaseline oil g - Mg sulphate 0.5 g - Aqueous extract of Xylopia aethiopica 3 g 15 - Theophylline g - Chrysanthellum indicum extract g - Demineralized water qs 100 g 4.) HIE gel emulsion for stressed man massage - Carbopol 981 (marketed by Goodrich) 0.6 g 20 - Ethyl alcohol 15 g - Volatile silicone oil g - Purcellin oil 7 g - Ginkgo Biloba extract 0.5 g - Perfume 0.4 g 25 - Tocopherol Nicotinate 0 1 g - Triethanolamine g - Aqueous extract of Xylopia aethiopica g - Natural caffeine 1.5 g - Demineralised water qs 100 g 30 Note that no preservative has proved useful in these formulas because Xylopia aethiopica from Guinea avoids proliferation microbial is particularly useful in case of iontophoresis in the course of which no preservative should be able to penetrate the skin. 40

Claims (10)

REVENDICATIONS1. Use of Xylopia aethiopica, as an adipocyte alpha-2 adrenergic receptor antagonist, alone or in combination with at least one other alpha-2-blocker in the preparation of a slimming composition for topical application. 2. Use of Xylopia aethiopica, as an alpha-2 adrenergic receptor antagonist, alone or in combination with at least one other alpha-2-blocker in the preparation of a cosmetic composition for the massage of the male body. 3. Use of Xylopia aethiopica according to claims 1 and 2, characterized in that only the fruit is used. 4. Use of Xylopia aethiopica according to claims 1 to 3, characterized in that the fruit is roasted before use. 5. Use of Xylopia aethiopica according to claims 1 to 4, characterized in that it can be combined with Ginkgo biloba, Chrysantellum indicum, Chrysantellum americanum, Hibiscus, ivy, escin. 6. Use of Xylopia aethiopica according to claims 1 to 5, characterized in that it can be combined with lipolytic active agents acting on adipocyte lipases such as xanthine bases and caffeine. 7. Use of Xylopia aethiopica according to claims 1 to 6, characterized in that the cosmetic compositions containing it are associated with a diet and / or sport. 8. Cosmetic composition according to claims 1 to 7, characterized in that the composition is in the form of an oil-in-water (O / W) or water-in-oil (W / O) emulsion, a multiple emulsion (H / W / O, W / O / W), microemulsion, twin-phase emulsion, PIT emulsion, nanoemulsion, pseudoemulsion (stable dispersion of two immiscible phases by means of gelling agent), aqueous gel, fatty gel, hydroalcoholic gel, fat phase, suspension, liquid or solid soap, foaming solution or not, freeze-dried gel or emulsion and / or one of the preceding forms 3containing microcapsules, nano-capsules, liposomes, ethosomes and which may occur without limitation in creams, liquids, pastes, lotions, emulsions, oils, gels, syrups, solids, powders, masks, sticks, tablets, sprays, aerosol, capsules, tablets, syrup and cocktails. 9. Cosmetic composition according to claims 1 to 8, characterized in that it contains no preservative. 10 10. A method of cosmetic treatment of the skin of the body for reducing localized fat overload or to allow the massage of the stressed man, characterized in that a composition containing as active ingredient at least Xylopia aethiopica as defined in one of claims 1 to 9.