MXPA00007660A - Topical composition containing tocopherol compound - Google Patents

Abstract

The present invention is concerned with a topical light screening composition comprising a) about 1wt%to 30wt%of a linear or cyclic polysiloxane compound of the general formula Ia or Ib, wherein X signifies R or A;A signifies a group of the general formula IIa, IIb or IIc;and wherein n, r, s, t and v and the R-symbols have the meaning given in the specification;and b) about 0.5wt%to about 15wt%of a tocopherol compound.

Description

TOPICAL COMPOSITIONS COMPRISING A COMPOUND OF TOCOPHEROL The present invention relates to topical compositions useful for preventing skin damage caused by ultraviolet irradiation, such as sunburn and premature aging of the skin induced by the sun. In particular, the invention relates to topical compositions consisting of a tocopherol compound and an agent for filtering UV-B type radiation, based on a lipophilic polysiloxane. Topical compositions containing tocopherol (vi-tamine E) and agents for UV filtering are already known in the art. US Patent No. 4,144,325 describes for example a composition for a sunscreen comprising a tocopherol compound and an ultraviolet absorption compound selected from the group consisting of the salicylates, para-aminobenzoates, benzophenone, cinnamate, naphthoate, gallate and mixtures thereof. Topical compositions containing tocopherol sorbate as the active agent, together with agents for solar filtering are described in US Patent No. 4,847,072. The agent for solar filtering is selected from the group consisting of the p-methoxycinnamate of 2-ethylhexyl, butylmethoxy dibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl dimethyl p-aminobenzoic acid, the ester of 4-N, N- (2 -ethyl-hexyl) methylaminobenzoic acid of 2,4-dihydroxy benzophenone, the ester of N, N-di- (2-ethylhexyl) -4-aminobenzoic acid of 4-hydroxy dibenzoylmethane, the ester of 4-N, N- ( 2-ethylhexyl) methylaminobenzoic acid of 4-hydroxydibenzoylmethane, the ester of 4-N, N- (2-ethylhexyl) methylaminobenzoic acid of 2-REF: 121753 hydroxy-4- (2-hydroxyethoxy) -ophenophenone, the ester of 4-hydroxyethylbenzoic acid -N, N- (2-ethylhexyl) methylaminobenzoic acid of 4- (2-hydroxy-ethoxy) dibenzyl ethane, the ester of NN-di- (2-ethylhexyl) -4-amino-benzoic acid of 2-hydroxy- 4- (2-hydroxyethoxy) benzophenone, the N, N-di (2-ethylhexyl) -4-aminobenzoic acid ester of 4- (2-hydroxyethoxy) dibenzoylmethane and mixtures thereof. The pharmaceutical / cosmetic compositions described herein may also include a penetration enhancing agent to enhance the penetration of tocopherol sorbate into the skin. The agent for enhancing penetration is p. ex. , N- (2-hydroxyethyl) pyrrolidone. It has now been discovered that the penetration rate of the tocopherol compounds can be enhanced by adding a lipophilic polysiloxane agent for the UV-B type filtrate, without an agent to enhance the subsequent penetration. Thus, the present invention relates to a topical composition comprising a) from about 1% by weight to 30% by weight of a linear or cyclic polysiloxane compound of general formula Ia or Ib, c + the Ib where X means R or A; A means a group with a general formula, Iib or He; Ilb R means hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; R1 and R2 each independently of one another mean hydrogen, hydroxyl, alkyl of 1 to 6 carbon atoms or alkoxy of 1 to 6 carbon atoms; R3 means alkyl of 1 to 6 carbon atoms; R 4 is hydrogen or alkyl of 1 to 6 carbon atoms; R5 and R6 each independently of one another mean hydrogen or alkyl of 1 to 6 carbon atoms; r has a value from 0 to 250; s has a value from 0 to 20; r + S has a value of at least 3; t has a value from 0 to 10; v has a value from 0 to 10; and v + t has a value of at least 3; n has a value of 1 to 6; with the proviso that in case s is 0, at least one X is A; and b) about 0.5% by weight to about 15% by weight of a tocopherol compound. As used herein, "tocopherol compound" refers to alpha tocopherol, mixed tocopherols, ester of a short chain carboxylic acid of tocopherol, such as p. ex. , tocopherol acetate, tocopherol propionate and tocopherol butyrate. As used here, "C 1-6 alkyl" refers to groups such as methyl, ethyl, propyl, isopropyl, n-butyl, sec. butyl, tere, butyl, pentyl and neopentyl. The term "alkoxy of 1 to 6 carbon atoms" refers to the corresponding alkoxy groups. The radical R is preferably alkyl of 1 to 4 carbon atoms, more preferably methyl. The radicals R1 and R2 may be the same or different. Preferably R1 and R2 have the same meaning and mean hydrogen, methoxy or ethoxy, more preferably hydrogen. The radical R3 preferably means methyl or ethyl, more preferably ethyl. The radical R 4 preferably represents hydrogen or methyl, more preferably hydrogen. The radicals R5 and R6 preferably represent hydrogen. n preferably has a value of 1. Polysiloxane compounds having a group A of general formula Ia and Ilb, and their preparation, are described in European Patent EP 0538431 Bl and EP 0709080 Al. These polysiloxane compounds are preferred. Polysiloxane compounds having a group A of general formula Ie and their preparation are described in European Patent EP 0358584 Bl. In the linear polysiloxane compounds according to the formula la, the radical A carrying the chromophore can be connected to the final groups of the polysiloxane (X = A, s = 0) or they can be statistically distributed (X = R, s> 0). Preferred are linear polysiloxane compounds wherein the radical A carrying the chromophore is statistically distributed. Said preferred polysiloxane compounds have at least one unit carrying the chromophore radical (s = 1), preferably having a value from about 2 to about 10, more preferably a statistical average value of about 4. The number of r of the other silicone units present in the polysiloxane compounds are preferably from about 5 to about 150, more preferably a statistical average value of about 60. The ratio between the polysiloxane units having a chromophore A radical of formula , and those having * a chromophore radical A of formula IIb is not critical. This ratio can be about 1: 1 to about 19: 1, preferably from about 2: 1 to about 9: 1, more preferably about 4: 1. The concentration of the polysiloxane compound in the topical composition is preferably about 2% by weight to 20% by weight, more preferably from about 5% by weight to about 10% by weight. The concentration of the tocopherol compound in the topical composition is preferably from about 1% by weight to about 10% by weight, more preferably from about 1% by weight to about 5% by weight. The ratio between the tocopherol compound and the polysiloxane compound as defined above is not critical. For example, the ratio is from about 1: 1 to about 1:20, preferably from about 1: 2 to about 1: 3. Thus, a preferred topical composition is composed of: from about 1% by weight to about 10% by weight of a tocopherol compound, and from about 2% by weight to 20% by weight of a polysiloxane compound linear, of general formula la, wherein X means methyl; A means a group of formula lia or 11b; R means alkyl of 1 to 4 carbon atoms; R1 and R2 have the same meaning and mean hydrogen, methoxy or ethoxy; RJ means methyl or ethyl; R "means hydrogen or methyl, Rs and R6 are hydrogen, r is about 5 to about 150, s is about 2 to about 10, n has a value of 1. A more preferred topical composition comprises: from about 1% by weight to about 5% by weight of tocopherol acetate, and about 5% by weight to about 10% by weight of a linear polysiloxane compound of general formula la, wherein X means methyl, A means a group of formula Ia or 11b; means methyl, R1 and R2 are hydrogen, means ethyl, R4 is hydrogen, R5 and R6 are hydrogen, r is a statistical average value of about 4, is a statistical average value of about 60; n has a value of 1 The polysiloxane compounds la or Ib wherein A is a radical of formula Ia or IIb can be prepared as described in patent EP 0538431 Bl by silylation of the corresponding benzalmalonates. The following reaction scheme shows an example for the preparation of a compound of general formula wherein R 4, R 5 and R 6 mean hydrogen and n has a value of 1. wherein R, R1, R2 and R3 are as defined above. The silylation of the 4- (2-propynylox) phenyl methylene diethyl ester can be carried out using known procedures for the addition of hydrogen atoms attached to the silicon to groups containing aliphatic unsaturation. These reactions are generally catalyzed by a metal of the platinum group or a complex of said metal. Examples of catalysts that can be used are platinum on carbon, chloroplatinic acid, platinum acetylacetonate, complexes of platinum compounds with unsaturated compounds p. ex. , olefins and divinyl disiloxanes, complexes of rhodium and palladium compounds and complexes of platinum compounds supported by inorganic substrates.

The addition reaction can be carried out under reduced pressure, atmospheric or high pressure. A solvent, e.g. ex. , toluene or xylene, in the reaction mixture although the presence of the solvent is not essential. It is also preferred to carry out the reaction at elevated reaction temperatures, e.g. ex. , from about 50 ° to about 150 ° C. The preparation of the new topical compositions comprises the incorporation of a polysiloxane compound as defined above and a tocopherol compound optionally in combination with other known filters for UV-A and / or UV-B, in a commonly used cosmetic base for topical compositions such as p. ex. , for agents for the filtering of light. The preparation of said topical composition is already well known to the person skilled in the art. Filters suitable for UV-B, ie substances having absorption maxima between about 290 and 320 nm, are for example, the following compounds: Acrylates such as 2-cyano-3, 3-diphenylacri-lato 2- ethylhexyl (octocrylene, PARSOL 340), ethyl 2-cyano-3, 3-diphenylacrylate and the like; Camphor derivatives such as 4-methyl ben-cylidene camphor (PARSOL 5000), 3-benzylidene camphor, al-camphor benzalkonium methosulfate, polyacrylamidomethyl benzylidene camphor, sulfobenzylidenecamphor, sulfomethylbenzylidenecamphor, terephthalenediandiphenol sulfonic acid and the like; Cinnamate derivatives such as octyl methoxycinnamate (PARSOL MCX), ethoxyethyl methoxycinnamate, diethanolamine methoxycinnamate (PARSOL Hydro), isoamyl methoxycinnamate and the like, as well as cinnamic acid derivatives linked to siloxanes; Pigments such as p. ex. , Ti02 microparticle-two. The term "microparticulate" refers to a particle size of about 5 nm to about 200 nm, in particular from about 15 nm to about 100 nm, The Ti02 particles may also be coated with metal oxides such as p. ex. , aluminum or zirconium oxides or organic coatings such as p. ex. , polyols, methicone, aluminum stearate, alkyl silane. Such coatings are already well known in the art. • Imidazole derivatives, such as p. ex. , 2-phenyl benzimidazole sulfonic acid, and its salts (PARSOL HS). Salts of 2-phenyl benzimidazole sulfonic acid are p. ex. , alkali salts such as sodium or potassium salts, ammonium salts, morpholine salts, salts of primary, secondary, and tertiary amines such as monoethanolamine salts, diethanolamine salts, and the like. Salicylate derivatives such as isopropylbenzyl salicylate, benzyl salicylate, butyl salicylate, octyl salicylate (NEO HFLIOPAN OS), isooctyl salicylate or homomenthyl salicylate (homosalate, HE-LIOPAN), and the like; Triazone derivatives such as octyl triazole (UVINULT T-150), dioctyl butamido triazone (UVASORB HEB) and the like. Suitable filters for UV-A, ie substances having absorption maxima between about 320 nm and 400 nm, are for example the following compounds: Derivatives of dibenzoylmethane such as 4-tert.butyl-4'-methoxydibenzoylmethane (PARSOL 1789), dimetho-xidibenzoylmethane, isopropyldibenzoylmethane and the like; - Benzotriazole derivatives such as 2,2'-me-tilen-bis- (6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) -phenol (TINOSORB M) and the like - Pigments such as, e.g., microparticulate ZnO The term "microparticulate" refers to a particle size of about 5 nm to about 200 nm, in particular from about 15 nm to about 100 nm The ZnO particles can also be coated with metal oxides such as, for example, aluminum or zirconium oxides or by organic coatings such as, for example, polyols, methicone, aluminum stearate, alkyl silane. well known in the specialty, as the dibenzoylmethane derivatives are photolabels, it is necessary to photostabilize these agents for UV-A filtering. Thus, the term "agent for common UV-A filtering" also refers to dibenzoylmethane derivatives such as p. ex. , Parsol 1789 stabilized by the following stabilizing agents, Derivatives of 3,3-diphenyl acrylate (octocrylene) as described in European Patent Publications EP 0514491 Bl and EP 0780119 Al; Derivatives of benzylidene camphor as described in US Pat. No. 5,605,680. As usual cosmetic bases for compositions for the filtering of light within the framework of the present invention, any conventional preparation corresponding to the cosmetic requirements, e.g. e. creams, lotions, emulsions, ointments, gels, solutions, sprays, pencils and milks; see also, "Sunscreens, Development, Evaluation and Regulatory Aspects" ("Solar filters, development, evaluation and regulatory aspects"), ed. N.Y. The e, N.A. Shaat, Marcel Dekker, Inc. New York and Bailesia, 1990. The following examples illustrate the invention in more detail, but do not limit its scope in any way. EXAMPLE 1 Preparation of an organosiloxane compound of the general formula wherein R means methyl, s is 0, r is 20, X is A and A is a benzalmalonate radical of formula Ia and wherein R 1 and R 2 are hydrogen, R 3 is ethyl and R4, R5 and R6 are hydrogen, n is 1 as described in EP 0538 431 Bl. 5 g of. { [4- (2-propynyloxy) phenyl] methylene} Diethyl ester was dissolved in 20 g of toluene and heated under nitrogen to about 80 ° C. 13.2 g of a hydrosiloxane with a degree of polymerization of 20 and 10 mpc (mol%) of SiH groups (3.62% SiH) were then added dropwise after adding also a platinum complex. di-inyl-tetramethyl-disiloxane, giving 10"4 moles of Pt per mole of SiH of the idrosiloxane The mixture was heated to reflux and maintained until all the SiH disappeared in the infrared spectroscopic analysis, then it was allowed to cool to room temperature The toluene was then evaporated to leave after washing, 16.5 g of a light brown polymer with the average structure A- [(CH3) 2SiO] 20-A, wherein A is a radical of formula Ilal and Ubi Ila1 Ilb1 Example 2 Preparation of an organosiloxane compound having the general formula wherein R means methyl, r is 59, s is 4, X is methyl and A is a benzalmalonate radical of formula Ia and IIb wherein R 1 and R 2 are hydrogen, R 3 is ethyl, R4 R5 and R6 are hydrogen as described in European Publication EP 0709080 A1. 13.28 g of. { [4- (2-propynyloxy) phenyl] methylene} Diethyl ester was dissolved in 75 g of toluene and heated under a nitrogen atmosphere at about 70 ° C. Next, 44 g of a hydrosiloxane with a degree of polymerization of 65 and 6 mpc of SiH groups (2.36% of SiH) were added dropwise after the addition of a complex of plati-no-divinyl-tetramethyl -disiloxane, giving 10"4 moles of Pt per mole of SiH of the hydrosiloxane The mixture was heated to reflux and maintained until all the SiH had disappeared from the infrared spectroscopic analysis, then it was allowed to cool to room temperature. toluene to leave after washing, 52 g of a brown viscous polymer with a middle structure (CH3) 3SiO- [(CH3) 2SiO] 59- [(CH3) ASiO] 4-Si (CH3) 3, where A has the formula Ilal and Ubi Ila1 Ilb1 The ratio between the compounds having an Ilal radical and the compounds having a Ubi radical is approximately 4: 1. EXAMPLE 3 Topical composition according to the invention, containing 5% by weight of polysiloxane. A topical composition containing 5% by weight of a polysiloxane of formula la, according to Example 2 and 2% by weight of tocopherol acetate, was prepared using the following ingredients: INCI: International Nomenclature of Cosmetic Ingredients ("International nomenclature of cosmetic ingredients") The compounds of part A were added and melted in a reactor. Compounds from part B were mixed, heated to 85 ° C and added to part _A. Finally SEPIGEL 305 was added at a temperature of 50 ° C. Example 4 Topical composition according to the invention, containing 10% by weight of polysiloxane. A topical composition containing 10% by weight of a polysiloxane of the formula according to Example 2, and 2% by weight of tocopherol acetate, was prepared using the following ingredients: The compounds of part A were added and melted in a reactor. Compounds from part B were mixed, heated to 85 ° C and added to part A. Finally, SEPIGEL 305 was added at a temperature of 50 ° C. Example 5 Comparative example EXAMPLE 6 Determination of Penetration Rate A lotion was applied as described in examples 3-5 on the skin of an intact physiologically isolated shaved rat; and percutaneous absorption was determined 16 hours after application. ' Experimental conditions: An area of 5 cm2 was marked in the center of the piece of skin and the test product was applied and distributed with a syringe. The syringe was weighed before and after each application of the test product to determine the exact amount of the test product applied. A small magnet was placed in the compartment of the bottom part of the penetration chamber. The skin sample was held in the penetration chamber. The receiving liquid was added until the compartment was completely filled and to ensure complete contact with the previous skin. The receptor phase was gently stirred by a magnetic stirrer throughout the experiment. The chamber was then connected to a thermostat and equilibrated at 32 ° C. After the penetration time, the chamber was disconnected from the thermostat and the applied product was recovered as follows: Surface of the skin: After opening the penetration chamber, the skin was removed and fixed on a plate (cork) and It was cleaned with cotton wool for several times, moistened with small amounts of EtOH / H20 1: 1 to facilitate the cleaning of the surface. The last time dried cotton was used. The cotton wool was extracted with 20 ml of acetonitrile and the extract was analyzed quantitatively by HPLC. Stratum corneum: The horny layer of the skin was removed with an adhesive tape. A piece of tape is placed on the skin with light pressure and extracted again. This procedure is called "stripping" ("stripping") and repeated (10 ± 6 times) until the skin shone and a moderate inflow of moisture indicated the total elimination of the stratum corneum. The adhesive strips were extracted with 15 ml of acetonitrile and analyzed quantitatively by HPLC. Naked skin: The application area was drilled, cut into small pieces with a scalpel and homogenized in 10 ml of 100% acetonitrile. It was then centrifuged and filtered, and the clear solution was analyzed quantitatively by HPLC. Receiving phase: The receiving liquid was collected (approximately 10 ml), the chamber was rinsed with 3 x 1 ml of acetonitrile, which was added to the receiving liquid, and the volume was adjusted to 15 ml. An aliquot of this solution was analyzed quantitatively by HPLC. The content of tocopherol acetate was analyzed by high performance liquid chromatography. The results (in% of the total amount of tocopherol acetate found in the samples) are summarized in the following table: average result of 4 measurements. The above table clearly shows that the polysiloxane compound enhances the penetration of the skin of tocopherol acetate. The bare skin contains 26-27% of the applied tocopherol acetate. It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects to which it relates.

Claims (14)

1. CLAIMS Having described the invention as above, property is claimed as contained in the following 1. A topical composition consisting of. a) from about 1% by weight to 30% by weight of a linear or cyclic polysiloxane compound of general formula Ia or Ib, the Ib characterized in that X means R or A; A means a group of general formula lía, I Ib or líe; Ilb R means hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; R1 and R2 each independently of one another mean hydrogen, hydroxyl, alkyl of 1 to 6 carbon atoms or alkoxy of 1 to 6 carbon atoms; R3 means alkyl of 1 to 6 carbon atoms; R 4 is hydrogen or alkyl of 1 to 6 carbon atoms; R5 and R6 each independently of one another mean hydrogen or alkyl of 1 to 6 carbon atoms; r has a value from 0 to 250; s has a value from 0 to 20; r + S has a value of at least 3; t has a value from 0 to 10; v has a value from 0 to 10; and v + t has a value of at least 3; n has a value of 1 to 6; with the proviso that in case s is 0, at least one X is A; and b) from about 0.5% by weight to about 15% by weight of a tocopherol compound.
2. 2. A topical composition according to claim 1, characterized in that the tocopherol compound is alpha tocopherol, a mixture of tocopherols or an ester of a short chain carboxylic acid, of tocopherol.
3. 3. A topical composition according to claim 2, characterized in that the short chain carboxylic acid ester of tocopherol is tocopherol acetate, tocopherol propionate or tocopherol butyrate, preferably tocopherol acetate. Four . A topical composition according to any one of claims 1 to 3, characterized in that R means alkyl of 1 to 4 carbon atoms, preferably methyl. 5. A topical composition according to any one of claims 1 to 4, characterized in that R 1 and R 2 have the same meaning and mean hydrogen, methoxy or ethoxy, preferably hydrogen. 6. A topical composition according to any one of claims 1 to 5, characterized in that R 3 signifies methyl or ethyl, preferably ethyl. 7 A topical composition according to any one of claims 1 to 6, characterized in that R 4 means hydrogen or methyl, preferably hydrogen. 8.. A topical composition according to any one of claims 1 to 7, characterized by park R and R mean hydrogen and n is 1. 9. A topical composition according to any one of claims 1 to 8, characterized in that X means R, s has a value from 1 to 20 and A is a radical of formula lia or Ilb. 10. A topical composition according to any one of claims 1 to 9, characterized in that a) from about 2% by weight to 20% by weight, preferably from about 5% by weight to about 10% by weight, weight of a linear or cyclic polysiloxane compound of general formula Ia or Ib, and b) from about 1% to 10% by weight, preferably from 1% by weight to 5% by weight of a tocopherol compound . 11. A topical composition according to any one of claims 1 to 10, characterized in that it consists of from approximately 1% by weight to approximately 10% by weight of a tocopherol compound, and approximately from 2% by weight to 20% by weight of a linear polysiloxane compound of general formula la, wherein X means methyl; A means a group of formula Ia or Ilb; R means alkyl of 1 to 4 carbon atoms; R1 and R2 have the same meaning and mean hydrogen, methoxy or ethoxy; RJ means methyl or ethyl; R * means hydrogen or methyl; R5 and R6 mean hydrogen; r is about 5 to about 150; s is about 2 to about 10; n has a value of 1. 12. A topical composition according to any one of claims 1 to 11, characterized in that it consists of from about 1% by weight to about 5% by weight of tocopherol acetate; and from about 5% by weight to 10% by weight of a linear polysiloxane compound, of general formula la, wherein X means methyl; A means a group of formula Ia or Ilb; R means alkyl of 1 to 4 carbon atoms; R1 and R2 have the same meaning and mean hydrogen-methoxy or ethoxy; RJ means methyl or ethyl; R * means hydrogen or methyl; R5 and R6 mean hydrogen; r is about 5 to about 150; s is about 2 to about 10; n has a value of 1. 13. A topical composition according to any one of claims 1 to 12, characterized in that, in addition, of common UV-A and / or UV-B filters. 14. The use of a topical composition according to any one of claims 1 to 12, as well as of an agent for filtering light.