FR2894810A1 - Composition useful to protect skin and/or superficial body growth against UV rays, comprises synergic association of Tinosorb-S and ectoine as UV-A photo protector - Google Patents

Abstract

Composition comprises synergic association of Tinosorb-S(RTM: 2,2'-[6-(4-Methoxyphenyl)-1,3,5-triazine-2,4-diyl]-bis-[5-(2-ethylhexyl)oxyl]-phenol) (I) and of ectoine ((4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid) (II) as a UV-A photo protector, where the weight ratio of (II) to (I) is at least 1:1000. An independent claim is included for a process for protection of skin and/or lips and/or superficial body growth against UV rays, comprising applying the composition on the skin and/or superficial body growth.

Description

The present invention relates to an association comprising Tinosorb-S

  (2,2 '- [6- (4-methoxyphenyl) -1,3,5-triazin-2,4-diol] bis [5- (2-ethylhexyl) oxyl] phenol) from Ecotoxic acid (carboxylic acid 1,4,5,6 tetrahydro) -2-methyl-, (S) -pyrimidine), for the manufacture of cosmetic or dermatological compositions intended for the protection of the skin and / or lips and / or phaners against ultraviolet radiation, and in particular solar radiation. Luminous radiation at wavelengths between 280 nm and 400 nm allows browning of the human epidermis, but wavelength rays between 280 and 320 nm (UV-B) cause erythema and burns. cutaneous. These burns are not only superficial, they can also induce phenomena of biological degradation which can lead to genomic mutations, it is essential and vital that this radiation is filtered.

  It is also known that rays with wavelengths between 320 and 400 nm (UV-A) are capable of inducing an alteration of the skin, in particular in the case of a sensitive skin or a skin. skin continuously exposed to solar radiation. UV-A rays in particular cause the formation of oxygen free radicals which causes damage to the genome. They promote aging and in some subjects may even originate phototoxic or photoallergic reactions. It is therefore also essential to filter the UV-A radiation as well. Most of the dermocosmetic and / or cosmetic compositions intended for the UV protection of the skin are quite often in the form of lotions, oils, oil-in-water O / W emulsions or water-in-oil emulsions. / H., And contain, in a cosmetically acceptable carrier, at various concentrations, one or more conventional organic filters, lipophilic and / or hydrophilic, capable of selectively absorbing harmful UV radiation, and possibly mineral or screen filters. The filters are associated according to the level of sun protection sought, the spectral area of protection sought, and the criteria of tolerance and stability of the formulations as a function of exposure times.

  These filters are not total filters, they can not protect the skin throughout the spectrum, some of the radiation reaches the epidermis nevertheless, especially because said UVA filters provide only a short protection in this area. Thus, there is still cellular damage induced by UV radiation reaching the living layers of the dermis and epidermis. Classically, to minimize this damage and extend the protection of spectra, they are combined and combined without achieving the desired result. Surprisingly, the Applicant has found that the combination of a UVA filter, conventionally used: TINOSORB S, with Ecotoxin or a physiologically acceptable salt of Ecotoxic, made it possible to obtain a level of sunscreen never obtained with combinations of filters Tinosorb S is the organic filter shown below, indexed in Chemical Abstracts under Registry Number 187393-00-6 whose name is: 2,2 '- [6- (4) This compound is known and marketed in particular by the company CIBA as a filter that can be incorporated into the cosmetic compositions compatible with the other filters as well. Organic and inorganic, its spectrum of protection is located in the UVA zone.

  Ectoine, a substance indexed in Chemical Abstracts under Registry Number 96702-03-3, is 1,4,5,6-tetrahydro-2-methyl-, (S) -4-pyrimidine carboxylic acid.

  By physiologically acceptable sets is meant salts obtained by reaction with mineral or organic bases capable of giving physiologically acceptable sets such as sodium, potassium, ammonium salts.

  Ectoine is a naturally occurring substance marketed by the company Merck KGaA for which an action of UV-induced damage protection at the cell level has been shown, see for example the article by J. Buenger et al. in Skin Pharmacology and Physiology, 2004; 17: 22-237.

  The tests conducted, and in particular the evaluation of the internal photoprotection against UVA by the so-called Comate Test (Photochem Photobiol., 2001, 74: 417-423), made it possible to demonstrate the synergistic improvement in the protection obtained. . The present invention relates to the use in admixture of TINOSORB-S (2,2 '[6- (4-methoxyphenyl) -1,3,5-tetrazine-2,4-diyl] bis [5- (2-ethylhexyl) oxyl] -phenol) and Ectoine (1,4,5,6-tetrahydro-2-methyl-, (S) -40pyrimidine carboxylic acid) for the formulation of compositions for skin photoprotection in the UVA spectrum.

  The compositions may further participate in skin photoprotection in the UVB spectrum and contain the appropriate actives. Elie also relates to compositions comprising a synergistic combination of TINOSORB-S (2,2 '[6- (4-methoxyphenyl) -1,3,5-triazine-2,4-diyl] bis [5- (2-ethylhexyl) oxyl] -phenol) and Ecto'ine (1,4,5,6-tetrahydro-2-methyl-, (S) -4-pyrimidine carboxylic acid) in a weight ratio Ectoine / TINOSORB-S of at least 1/1000.

  The compositions according to the present invention comprise, in a physiologically acceptable medium, from 0.5 to 20% of Tinosorb S (2,2 '[6- (4-methoxyphenyl) -1,3,5-triazine-2,4-diyl). ] -bis- [5- (2-ethylhexyl) oxyl] -phenol) relative to the total weight of the composition, and from 0.005 to 10% of Ectoine (1,4,5,6-tetrahydro-2-carboxylic acid). methyl -, (S) -4-pyrimidine) by weight relative to the total weight of the composition. In a particular embodiment, the compositions according to the invention comprise from 1 to 10% of TINOSORB-S (2,2 '- [6- (4-methoxyphenyl) -1,3,5-triazine-2,4- diyl] bis [5- (2-ethylhexyl) oxyl] -phenol) and from 0.005 to 2% of Ectoine (1,4,5,6-tetrahydro-2-methyl-, (S) -4-pyrimidine carboxylic acid) The invention also relates to the use of a synergistic combination of TINOSORB-S (2,2 '[6- (4-methoxyphenyl) -1,3,5-triazine). 2,4-diyl] bis [5- (2-ethylhexyl) oxyl] -phenol) and Ectoine (1,4,5,6-tetrahydro-2-methyl-, (S) -4-pyrimidine carboxylic acid) ) for the preparation of a composition with improved activity of skin photoprotection in the UVA spectrum.

  The compositions according to the invention may furthermore comprise other active principles capable of completing this photoprotection in the UVA spectrum and of conferring protection in the UVB spectrum.

  Among the active ingredients which can complete the action of the synergistic combination according to the invention, mention will be made of the active compounds as photoprotective agents in the UVA and / or UVB. These photoprotective agents, well known to those skilled in the art, are marketed by chemical companies, such as the companies BASF, HAARMANN and REINER, HOFFMANN LAROCHE, MERCK, AMERICAN CYANAMID or CIBA and are listed in the CTFA directory (Cosmetic Toiletry and Fragrance Association). ). Other filters today referred to as inorganic filters, as opposed to the above-mentioned organic filters, may also be incorporated in the compositions according to the invention, for example, pigments, metal oxides or pearlescent agents.

  Said sunscreens or active photoprotective agents in UV-A and / or UV-B are chosen, for example, from para-aminobenzoic acid derivatives, salicylic derivatives, cinnamic derivatives, benzophenone derivatives, benzylidene camphor derivatives, benzimidazole derivatives, triazine derivatives, benzotriazole derivatives, anthranilic derivatives, imidazoline derivatives and mixtures thereof.

  By way of example, mention may be made of the filters or photoprotective agents marketed under the following names and / or brands, Amerscreen P marketed by Amerchol, UVINUL P25 by BASF, EUSOLEX HMS by RONA / EM, NEO HELIOPAN TS marketed by HAARMANN and REIMER, PARSOL 1789 marketed by HOFFMANN LAROCHE, HELISORB 11 marketed by NORQUAY, SPECTRA-SORB UV-24 marketed by AMERICAN CYANAMID, MEXORYL SD marketed by CHIMEX, UVASORB HEB marketed by SIGMA 3V, MIXXIM BB / 100 marketed by FAIRMOUNT CHEMICAL.

  Mineral filters are, for example, nacres, pigments, or else nanopigments of coated or uncoated metal oxides, such as nanopigments of titanium oxide, iron oxide, zinc oxide, zirconium oxide or cerium oxide and their mixtures. which are also UV photoprotective agents. Conventional coating agents are moreover alumina and / or aluminum stearate.

  The compositions according to the present invention may further comprise cosmetic and / or dermatological active agents. Among the active agents that may be mentioned as examples are antioxidants, anti-radical fiber agents, vitamins and anti-inflammatories.

  The compositions of the invention may also comprise conventional adjuvants used in cosmetics and / or in dermocosmetics, these will in particular be chosen from fatty substances, organic solvents, emulsifiers, ionic or nonionic thickeners, softeners, opacifiers, stabilizers, emollients, silicones, antifoam agents, moisturizers, vitamins, perfumes, preservatives, surfactants, fillers, polymers, propellants, basifying or acidifying agents, dyes or any other ingredient usually used for the manufacture of compositions for sunscreen and more particularly in the form of emulsion.

  Fatty substances may consist of an oil or a wax or their mixtures, and they also include fatty acids, fatty alcohols and esters of fatty acids.

  The oils may be chosen from animal, vegetable, mineral or synthetic oils and in particular from liquid petroleum jelly, paraffin oil, volatile or non-volatile silicone oils, isoparaffins, polyolefins, fluoro and perfluorinated oils. . Similarly, the waxes can be chosen from animal waxes, fossils, vegetates, minerals or syntheses. By way of example, mention may be made of polar oils, marketed as, for example, Finsolv TN, tridecyl trimellitate, isononyl isononyl ester, isopropyl myristate, decaprylyl carbonate, alcohol benzoates and hydroxybenzoates. of Guerbet, like the Hallbrite BHB of CP Hall Company.

  The compositions of the invention may be prepared according to known and described techniques, in particular those for the preparation of oil-in-water (O / W) or water-in-oil (W / O) emulsions. When the compositions are in emulsion form, they may be simple or complex: double (W / E or W / O) or triple (W / O / W or W / E / H). The final form of the compositions may then be a cream, a milk, a gel or a cream gel, a powder, a solid baton and optionally it may be packaged in aerosol and be in the form of foam or spray. The composition according to the invention can also be in the form of a suspension or dispersion in solvents or fatty substances, in the form of a nonionic vesicular dispersion. The final form may also be a cream or a milk, an ointment, a gel, a cream gel, a solid stick, a powder, a stick, an aerosol foam or a spray. When the cosmetic composition according to the invention is used for the protection of phaneres, such as hair against UV rays, it can be in the form of shampoo, lotion, gel, emulsion, or non-ionic vesicle dispersion. or a treatment product such as conditioners or lotions When the composition is used as a makeup product for nails, eyelashes, eyebrows or skin, such as foundation, lipstick, makeup The invention also relates to the use of a composition according to the invention in or for the manufacture of cosmetic compositions, in the form of solid or pasty, mascara or liner, it may be in solid or pasty form, anhydrous or aqueous. or dermatological agents for the protection of the skin and / or phaneres against ultraviolet radiation.

  The composition may be used in the formulation of self-tanning product and / or artificial browning of the skin; The invention therefore also relates to a composition according to the invention characterized in that it further comprises at least one agent for tanning and / or artificial browning of the skin, the activity has been demonstrated inter alia by the test. described and the result obtained with cultures of melanocytes on which we have researched the level of genomic protection confirms the synergistic activity on the protection in the spectrum of the UVA, of the association according to the invention EXAMPLE 1 Capacities The internal photoprotection of E. coli (Ect, 12 mM) and the external photoprotection of a cream comprising the combination according to the invention against UVA radiation (365 nm) were evaluated by the comets test on primers. cultures of normal human melanocytes (Photochem Photobiol., 2001, 74: 417-423) Internal photoprotection was measured after a treatment of 120 min at 37 C. The irradiation dose was 0.8 J / cm 2 for UVA radiation (365 nm). The comets test was carried out immediately after irradiation. Negative controls included untreated and unirradiated melanocytes and melanocytes treated by both mixtures and not irradiated. The parameter was the UVA genomic protection coefficient (CPGuvA) •

The protocol is as follows:

  1. Culture of melanocytes Normal human melanocyte cultures (MHN) are made from prepuces of children and newborns before phimosis. Melanocytes obtained from skin fragments are placed in MCDB 153 medium (Sigma St Louis, MO, USA) supplemented with 30 μg / ml bovine pituitary extract (BPE) (Life Technologies, Paisley, England), 2% of fetal calf serum (FCS) (Dominique Dutscher, Brumath, France), 16 nM of phorbol-12-myristate-13-acetate (Sigma), 5 μg / ml of insulin and 1.1 μM of hydrocortisone (Sigma) . The cultures are maintained in an incubator at 37 ° C. and under an atmosphere containing 5% of CO2. Pure cultures of melanocytes are obtained after 2 to 3 weeks.

  2. Preparation of the slides and irradiation of the cells After treatment with a trypsin / EDTA mixture (0.05% / 0.02%) for 2 to 3 minutes, the cells are recovered by centrifugation and placed in Ca-free PBS buffer. and without Mg "(Sigma). Following a second centrifugation, the cells (4.5-5.0x104 cells) are suspended in 0.5% Low Melting Point agarose, LMP (Sigma). The mixture is directly deposited on microscope slides coated with a pre-layer of agarose (1.6%) dried overnight at room temperature and freshly precoated with a second layer of agarose (0.8%). A fourth layer of LMP agarose is finally deposited to trap the keratinocytes.

  UVA irradiations are generated by a Bio-Sun UV irradiator (Vilbert Lourmat, Marne la Vallee). This device is equipped with monochromatic lamps that emit at 365 nm wavelengths. The lamps emit a calculated energy, using a RMW-365/312 type radiometer of 4.0 mW / cm2 for UVA, and the energies are 0. 8 J / cm2 for UVA. the cells are irradiated on an ice bath and the comets test is carried out immediately after exposure.

  3. The comets test (dry slides technique) The comets test protocol is that of De Meo et al. [De Meo M, Laget M, Castegnaro M, Dumenil G. Genotoxic activity of potassium permanganate in acidic solutions. Mutation Res. 1991; 260; 295-306.1 by incorporating the technique of dry slides [Klaude M, Ericksson S, Nygren J., Annstrom G. The comet assay: mechanism and technical consideration. Mutation Res. 1996; 363; 89-96]. The slides are placed after the irradiations in a lysis bath (2.5 M NaCl, 100 mM Na 2 EDTA, 10 mM Tris-HCl pH 10, 1% sodium sarcosinate, 1% Triton X-100 and 10% DMSO). . The cell lysis is carried out at 4 ° C. for 60 min followed by the denaturation of the DNA at room temperature for 20 min in a strongly alkaline solution (1 mM Na 2 EDTA and 300 mM NaOH, pH> 13.0). After electrophoresis (25V, 300 mA) for 20 min, the slides are neutralized with Tris-HCl buffer (04 M, pH 7.4) and dehydrated in ethanol or absolute methanol 4. Microscopic observation and analysis Image

  The slides are stained with ethidium bromide solution (75 NI 2 μg / ml) and observed with a BH2-RFL fluorescence microscope (Olympus, Japan) equipped with a 20BG-W dichroic filter. (excitation: 515-560 nm, emission: 590 nm) and an Apo D-Plan 20x objective The image analysis is performed with a monochrome CCD camera high sensitivity (Cohu 4912-5000) coupled to a map The Matrox IP-8 acquisition set is driven by Fenestra Komet software (Kinetic Imaging, Liverpool, UK, version 3.1).

  A total of 100 cells per sample (50 cells / slide) is analyzed. The parameter used is "Tail Moment" (TM which is defined as the product of the percentage of DNA in the comet's tail by the length of the comet (pm).) For each series of experiments, a negative control (cells non-irradiated) and positive control (irradiated cells without screen) are included.

  5. Statistical analysis Nonlinear regressions based on a function x2 are computed directly from the TM distribution frequencies for each sample. Indeed, Bauer and Coll [3] recently showed that these distributions followed a function x2. This method is based on an analysis of the distribution according to a law of x2 whose formulas are as follows: P (x2) = 5 10 With F (n / 2) = gamma function n T 2 = ce-`* t 2dt The factor n (also called x2 TM) which represents the degree of freedom of function is directly correlated with the degree of lesion (mean TM). The factor n varies from 2 (intact cells) to 15 (cells extremely low with a Gaussian distribution frequency). The degree of freedom (n) can be used as an indicator of DNA damage. The distribution frequencies are computed with the Excel 97 Spreadsheet (Microsoft) and the non-linear regressions are computed with the 2D Table Curve software (Jandel Scientific, version 5.0). Finally, the genomic protection coefficients (CGP) are computed with the formula CGP (%) = 1 x 2 TMse ù x 2TM`-] xioo x TMc + ù x TMc With f -TMsc: f-TM of the sunscreen; fTMc_: x2-TM non-irradiated control; f-TMc +: f-TM irradiation control The formula of Creme test ~ e 5SM05 (Cr5S) is as follows: Ingredients% Quantities for 300g Cetiol CC 30 90 Monostearate glycerine 2 6 Tinosorb S 1,5 4,5 Demineralized water 55 , 50 166.47 Propylene glycol codex 5 Uniphen P23 0.5 1.5 Amphisol K 3 9 Sepigel 305 1.5 4.5 (shake before use) Demineralized water 1 3 The various phases are prepared and emulsified under heat conditions The Ectopin is then incubated with the emulsion obtained, the results of which are summarized in the following Table.

  UVA only UVA + Tinosorb S UVA + Ecthony UVA + Tinosorb S + Ectoine15 Condition OTM-X2 Protection degree (%) NI 2.15 0.15 100.0 UVA (0.8 J / cm2) 8.71 0.42 0 UVA + Tinos (1.5%) 5.10 0.18 55.0 UVA + Ecto (2 mM) (0.285 g / I) 7.69 0.30 22.4 UVA + Tinos (1.5%) + Ecto (2 2.94 0.14 94.8 mM) The results obtained show that there is a synergistic improvement with the combination according to the invention. . OTM-X2 Tail Moment x2. Degree of freedom of function calculated by nonlinear regression of the standard OTM distribution frequency. The probability of the models in all cases is P <0.001.

  • NI: non-irradiated melanocytes • UVA: melanocytes irradiated by UVA (0.8 J / cm2) • UVA + TinoS: melanocytes irradiated by UVA radiation (0.8 J / cm2) and protected by a cream whose formula is described above. • UVA + Ecto: melanocytes irradiated with UVA radiation (0.8 J / cm2) and pretreated with Ecotoxon (2 mM) (0.285 g / () for 30 min • UVA + TinoS (1.5%) + Ecto (2 mM) (0.285 g / I): melanocytes irradiated with UVA radiation (0.8 J / cm 2), protected by a cream 20 whose formula is described above and prepared by E. coli (2 mM ) (0.285 g / I) for 30 minutes

  Examples of formulas employing the synergistic combination according to the invention are described below.

  Examples of formulations Formulas 1 to 3 below illustrate the invention. Formula 1 EthoxyDiglycol & Cucumber Isostearyl Isostearate Tinosorb S Dimethicone trimethylsiloxysilicate Tocopheryl Acetate Water Sucroester Glycerine Ectoine Creatine Butyl, Methyl, Propylparaben + Phenoxyethanol 15 Perfume Formula 2 Tinosorb S 20 Butyl Methoxydibenzoylmethane Octyl Triazone Glyceryl Stearate Cetyl Alcohol Dimethicone 25 Coco Caprylate / Caprate PVP / Eicosene Copolymer Potassium Cetyl Phosphate Methylparaben & Propylparaben Disodium EDTA 30 BHT Water Carbomer Ectoine Ergothioneine 35 Crodamol DA 8.00% 5.00% 2.00% 3.00% 0, 20% 66.20% 5.00% 5.00% 0.02% 0.50% 0.40% 0.20% 1.00% 3.00% 2.00% 4.00% 0.50% 0.50% 8.00% 2.00% 2.00% 0.25% 0.10% 0.05% 27.05% 10.00% 0.01% 0.01% 5.00% Potassium Hydroxide 0.45% Water 20.00 % Phenylbenzimidazol Sulfonic Acid 2.00% Potassium Hydroxide 3.60% Tocopheryl Acetate 2.50% Panthenol 1.00% Perfume qs 100% Formula 3 Cetiol CC 2.00% Caprylic / Cap ric Triglyceride 4.00% Octyl stearate 3.00% Tinosorb S 2.00% Benzophenone-3 1.00% Fragrance 0.30 0/0 Polyglyceryl-3 Diisostearate 4.00% PEG-20 Glyceryl Laurate 1.00% Water 66.95% Carbomer 0.4% Propylene Glycol 2.00% Phenoxyethanol & Methylparaben & Propylparaben 0.50% Xanthan Gum 0.30% Triethanolamine 0.85% Phenylbenzimidazole Sulfonic Acid 2.5% Water 3.85% Acetyl Tyrosine 2% Ectoine 0.02 %

Claims (1)

  1. Composition comprising a synergistic association, with respect to photoprotection in the UVA spectrum, of TINOSORB-S (2,2 '[6- (4-methoxyphenyl) -1,3,5-triazine-2,4- diyl] bis [5- (2-ethylhexyl) oxyl] phenol) and Ectoine (1,4,5,6-tetrahydro-2-methyl-, (S) -4-pyrimidine carboxylic acid) in a weight ratio EctoIne / TINOSORB-S of at least 1/1000. 3. Composition according to claim 1, characterized in that it comprises from 1 to 10% of TINOSORB-S (2,2 '[6- (4-methoxyphenyl) -1,3,5-triazine-2,4- diyl] bis [5- (2-ethylhexyl) oxyl] phenol) and from 0.005 to 2% Ecto'ine (1,4,5,6-tetrahydro-2-methyl-, (S) -4 carboxylic acid -pyrimidine) by weight relative to the total weight of the composition. 4. Composition according to one of the preceding claims, characterized in that it further comprises at least one UV filter or a photoprotective agent 5. Composition according rune preceding claims, characterized in that it further comprises nacres, Metallic oxides, whether or not coated, pigments or nano-pigments 6. Use of a synergistic combination of TINOSORB-S (2,2 '[6- (4-methoxyphenyl) -1,3,5-triazine-2 , 4-diyl] bis [5- (2-ethylhexyl) oxyl] -phenol) and Ectoine (1,4,5,6-tetrahydro-2-methyl-, (S) -4-pyrimidine carboxylic acid) for the preparation of a composition having improved activity of skin photoprotection in the UVA spectrum. 7. Use of a composition according to one of claims 1 to 5 in or for the manufacture of cosmetic or dermatological compositions for the protection of the skin and / or phaneres against ultraviolet radiation. A method for protecting the skin and / or the lips and / or phaneres against UV radiation, characterized in that it consists in applying to the skin and / or the phaneres a cosmetic composition according to one of Claims 1 to 5.