COSMETIC PREPARATIONS CONTAINING UBIDECARENONES

Abstract: Ubidecarenones are effectively dissolved in aqueous media by means of N-acyl-2-amino-ethanesulphonates, wherein the acyl residues have more than 5 carbon atoms. Cosmetic compositions containing ubidecarenones so solubilized are particularly effective in anti-aging and hydrating treatment.

Description: "COSMETIC PREPARATIONS CONTAINING UBIDECARENONES" The present invention relates to cosmetic prepara tions containing soluble ubidecarenones prepared b disperding in acqueous media mixtures having different ratios of ubidecarenones and acyl derivatives of 2-amino- ethansulphonic acid. The ubidecarenones form an important class of lipo- soluble vitaminic principles, particularly 2, 3-dimethoxy- 5-methyl-8-decaprenyl-l,4-benzoquinone, known as ubideca- renone-10, localized at the mitochondrial level, plays a key-role in mammals in the electron-transfer system and more generally in the energy production. Because of said important metabolic, roles, the ubiquinone-10 is widely used in a large number of cardiac pathologies, protecting the myocardium from ischemic phe- nomena and preserving the functions thereof. Moreover, because of the ability of ubidecarenone- 10 of influencing both the tissutal respiration and the peroxidative phenomena of the cellular membranes, said vitamin is particularly interesting for the prevention of tissutal aging phenomena, particularly of the skin, which the recent biochemical knowledges ascribe, inter alia, to the action of free radicals, responsible of the structural alteration of the membrane lipids. The development of biocompatible, hydrosoluble formulations is of particular interest for a better bio- availability of ubidecarenone-10 both in the pharmaceuti¬ cal and cosmetic use. The present invention concerns the development of a system able to carry in aqueous media the ubidecarenones, thanks to the interaction with amphipatic ions of general formula RNH-CH -CH -SO , wherein R is an acyl radical having more than 5 carbon atoms, preferably a natural fatty acid of the normal, iso, anteiso series or cycloal¬ kyl, saturated or unsaturated having from 8 to 26 carbon atoms. This class of amphipatic molecules is surprisingly able to carry the ubidecarenones in water, in form of micellar and/or liposomial aggregates, even using an equi- molar ratio of the two compounds. A molar excess of the amphipatic solubilizing spe¬ cies is preferably used, from 2 to 4 times higher than the vitamin, said conditions granting a better and faster solubilization. The preparation of hydrosoluble ubidecarenones may be carried out in different ways, for instance by sonicating an acqueous solution of the amphipatic species, to which the ubidecarenone is added or preferably by dispersing in water, under vigorous stirring, a mixture of ubidecarenone and N-acyl-2-amino-ethanesulphonate, prepared by evaporation of a solution of the two compounds in an organic solvent, in which both are soluble. The micellar and/or liposomial systems so prepared are stable over long periods of time, even at extremely low or high environmental temperatures, that may be more¬ over lyophilized, yielding generally materials of waxy consistency, easily soluble in water by simple stirring. The advantages attained by the invention in the cosmetic use are: a) the possibility of using hydrating, non-oily prepara- tions, also in combination with other active princi¬ ples; b) a good absorption of the active principle by the derma,- because of its micellar and/or liposomial organization; c) a good tolerability even in prolonged treatments; d) the possibility of sterilizing by filtration the prepa¬ ration thanks to its reduced size and to the stability of the micellar and/or liposomial aggregates; e) the possibility of modulating the characteristics of the preparation by changing the acyl residues of the solubilizing agent. The invention provides therefore cosmetic composi¬ tions containing as the active principle compounds of ubi¬ decarenone and N-acyl-2-amino-ethanesulphonates optionally in admixture with conventional cosmetic excipients. The compositions of ubidecarenone and N-acyl-2-ami- noethansulphonates find specific use in the cosmetic field in the prevention of tissutal aging phenomena. Said action exerted by ubidecarenone is to be ascribed to a specific protective mechanism from the peroxidative phenomena on the double bonds of the membrane unsaturated fatty acids and to the specific roles of this vitamin in the cellular respiration processes. The procedures generally described in the present invention, because of their simplicity or limited cost, are easily suited to the development of preparative pro¬ cesses on the industrial scale. The cosmetic preparations of the invention are prepared according to well-known methods and using conven- tional excipients such as those described in "Remington's Pharmaceutical Sciences", Hack Pub. Co., N.Y., USA. Exam¬ ples of said preparation are creams, lotions, also in form of sprays, containing from 0.5 to 10% by weight of an hydrosoluble ubiquinone derivative, particularly of ubide- carenone-10. Other cosmetically active substances may be used in combination with the ubidecarenone derivatives of the invention. The compositions are applied to the skin in the usual amounts in order to achieve the desired cosmetic effects, for instance anti-aging and hydrating effects, cellular regeneration, stimulation of the hair growth, protection from damages induced by UV radiations, an¬ ti-wrinkles and anti-scurf effects. The following examples illustrate the preparation of different kinds of soluble ubidecarenones. They neces¬ sarily concern only some of the numerous possibilities which can be envisaged and, without any limitative cha¬ racter, they only define the scope of the invention. EXAMPLE 1 62.5 g of 2-amino-ethansulphonate, suspended in 500 ml of anhydrous dimethylformarαide, were reacted at 70°C for 10 hours with 410 g of oleic anhydride, in the presen¬ ce of 0.5 g of dimethylaminopyridine as a catalyst. After evaporation of the solvent under vacuo, the oily residue was repeatedly triturated in ethyl ether. 190 g of N-oleyl-2-amino-ethansulphonate as a waxy, white solid, were obtained. 2 2 T Thhee HH--NNMMRR ssppectrum in CDC1 shows the signal of the acyl moiety, in the correct integration ratio, at o 5.3; 2.4; 1.9; I.r.: 1.3 and 0.9 and those of 2-amino- ethanesulphonate at 3.7 and 4.6. 86.2 g of ubidecarenone-10 were added to 81 g of N-oleyl-2-aminoethansulphonate, dissolved in 2.8 liters of water. The obtained biphasic system, after sonication, yields an homogeneous phase of micellar and/or liposomial kind, stable in time and to the environmental parameters. For instance, freezing of the solution or its heating do not change the chemico-physical state of the dispersed supermolecular aggregates. EXAMPLE 2 87.5 g of 2-amino-ethanesulphonate, suspended in 500 ml of anhydrous pyridine, were reacted at 50°C for 10 hours with 311 g of linolenic acid chloride. After evaporation of the solvent under vacuo, the oily residue was first triturated in ethyl ether and then, dissolved in water, was dialyzed against water. After lyophilization 255 g of N-linoleyl-2-amino-ethanesulphona- te as a white, waxy solid, were obtained. The H -NMR spectrum recorded in CDC1_ shows, in the correct integra¬ tion ratios the signals of the acyl moiety at o 5.3; 2.8; 2.4; 1.9;1.6;1.3;0.9 and those of 2-amino-ethanesulphonate at 3.7 and 4.6. 172 g of ubidecarenone-10 and 321 g of N-linoleyl- 2-amino-ethanesulphonate were dissolved in 2 1 of 1 CHC1 . After evaporation of the solvent under vacuum, 3.4 liters of water were added under vigorous stirring. An homogeneous system, yellow-orange in colour, of micellar and/or liposomial kind, stable in time and to the environ- mental parameters was obtained. EXAMPLE 3 43.1 g of ubidecarenone-10 and 64.2 g of arachido- nyl-2-amino-ethanesulphonate were dissolved in 1 1 of CHC1 . After removal of the solvent, 2 1 of water were added under vigorous stirring, till the formation of a stable micellar and/or liposomial system. After freezing and lyophilization of the solution a waxy compound orange in colour, readily soluble in the presence of water, was obtained.

Claims: CLAIMS 1. Hydrosoluble ubidecarenones derivatives obtained by addition to the ubidecarenones of N-acyl-2-amino-ethane- sulphonate wherein the acyl residue has more than 5 carbon atoms and is preferably a natural fatty acid, saturated or unsaturated of the normal, iso, anteiso or cycloalkyl series, having from 8 to 26 carbon atoms. 2. Cosmetic compositions containing as the active principle an hydrosoluble ubidecarenone derivative accor¬ ding to claim 1, optionally in combination with other active principles, in admixture with the usual excipients and vehicles.

Inventors: DE ROSA MARIO, ZAPPIA VINCENZO, DE ROSA, MARIO, ZAPPIA, VINCENZO
Applicants: ARVAL SPA, ARVAL S.P.A.
Application year: 1987
Main classification: A61K7
IPC codes: A61K8, A61K9, A61K31, A61K47, A61Q19