FR2894141A1 - SKIN DEPIGMENTING COMPOSITION COMPRISING A NAPHTHOTIC ACID DERIVATIVE - Google Patents

Abstract

The invention relates to a depigmenting composition of the skin comprising, in a physiologically acceptable medium, an enantiomer or a mixture of enantiomers of a naphthoic acid derivative, its pharmaceutical or cosmetic use. The invention also relates to a depigmenting composition of the skin comprising, in a physiologically acceptable medium, an enantiomer or a mixture of enantiomers of a naphthoic acid derivative and at least one other depigmenting agent, and / or a filter solar, its pharmaceutical or cosmetic use.

Description

The invention relates to a depigmenting composition of the skin

  comprising, in a physiologically acceptable medium, 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) - 1-propynyl] benzoic acid, and in particular one enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5) 5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid, and its pharmaceutical or cosmetic use. The composition according to the invention may also comprise another depigmenting agent, and / or a sunscreen.

  Many skin products are now described as depigmenting agents such as hydroquinone or azelaic acid. A. M. Kligman describes in US Pat. No. 3,856,934 a depigmenting composition comprising hydroquinone, retinoic acid and a corticosteroid. This type of association allows good depigmentation of the skin but causes significant adverse effects such as irritation and itching.

  The discovery of new compounds effective in the disorders of pigmentation is always of great interest. The Applicant has surprisingly discovered that the use of 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl) -2 1-propynyl] benzoic acid, and especially of one enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-3- (5,6,7 8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl-1-propynyl] benzoic gave a good depigmenting activity.

  2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid is the compound of the following formula (I): OH COOH (0) The carbon bearing the hydroxyl group at the 3-position of the propynyl chain (Cl is asymmetric, and can therefore be of R or S configuration, which corresponds to the two possible enantiomers of the molecule .

  The invention thus relates to a depigmenting composition of the skin comprising in a physiologically acceptable medium, 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5 8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid. Preferably, the composition comprises an enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8 8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid.

  The invention also relates to a depigmenting composition of the skin comprising in a physiologically acceptable medium, 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5 , 8, 8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid, and preferably one enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-3- ( 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid, and at least one other depigmenting agent. Physiologically acceptable medium means a medium compatible with the skin, mucous membranes and / or integuments.

  By depigmenting agent is meant any active agent having a depigmenting activity of the skin. This activity makes it possible to reduce the already existing pigmentation of the skin and also to prevent any additional pigmentation superior to the natural pigmentation.

  Mention may be made, as a depigmenting agent, by way of non-limiting example, of phenol derivatives, such as hydroquinone, hydroquinone monoethyl ether, hydroquinone monobenzylether or 4-hydroxyanisole; kojic acid and its derivatives; azelaic acid and its derivatives; linoleic acid; resorcinol and its derivatives; ellagic acid; hydroxy acids such as glycolic acid; ascorbic acid and its derivatives, in particular ascorbyl glucoside; zinc peroxide; and mercury chloride, arbutin and its derivatives such as those described in EP-895,779 and EP-524,109; aminophenol derivatives such as those described in applications WO 99/10318 and WO 99/32077, and in particular N-cholesteryloxycarbonyl-para-aminophenol and N-ethyloxycarbonyl-para-aminophenol; iminophenol derivatives, in particular those described in application WO 99/22707; L-2-oxothiazolidine-4-carboxylic acid or procysteine, as well as its salts and esters; and plant extracts, in particular licorice, mulberry and skullcap.

  In particular, the depigmenting composition of the skin may comprise, as depigmenting agent, a phenolic derivative, and in particular hydroquinone or 4-hydroxyanisole.

  Preferably, the composition according to the invention advantageously comprises between 0.0001 and 20% by weight of an enantiomer or of a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-acid 3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic relative to the total weight of the composition, preferably between 0.001 and 10% by weight; weight.

  To give an order of magnitude, the composition according to the invention advantageously comprises between 0.0001 and 20% by weight of an enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [ 3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic relative to the total weight of the composition and between 0.0001 and 20% by weight of depigmenting agent relative to the total weight of the composition, and preferably, respectively, between 0.001 and 10% by weight of an enantiomer or a mixture of enantiomers in all proportions of the acid 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid by weight total of the composition and between 0.025 and 10% by weight of depigmenting agent relative to the total weight of the composition.

  The depigmenting composition of the skin according to the invention may further comprise at least one sunscreen.

  Among the sunscreens, mention may be made, by way of non-limiting example, of the physical sunscreens such as titanium dioxide, zinc oxide and chemical sunscreens such as octocrylene, ethylhexyl methoxycinnamate, octyl salicylate, avobenzone, oxybenzone, ecamsule or trisiloxane drometrizole or mixtures thereof. Each sunscreen may be added at a concentration ranging from 0.001% to 20% by weight relative to the total weight of the composition.

  The compositions according to the invention may furthermore comprise any additive usually used in the cosmetic or pharmaceutical field, such as sequestering agents, antioxidants, preservatives, fillers, electrolytes, humectants, dyes, bases or acids. common, mineral or organic, perfumes, essential oils, cosmetic active ingredients, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds, soothing and protective agents for the skin such as allantoin . Of course those skilled in the art will take care to choose this or these optional additional compounds, and / or their amount, such that the advantageous properties of the composition according to the invention are not, or not substantially impaired.

  These additives may be present in the composition in a proportion of 0.001 to 20% by weight relative to the total weight of the composition.

  Mention may be made, as an example of sequestering agents: ethylenediamine tetracetic acid (EDTA), as well as its derivatives or its salts, dihydroxyethylglycine, citric acid, and tartaric acid.

  Examples of preservatives include benzalkonium chloride, phenoxyethanol, benzyl alcohol, diazolidinyl urea, and parabens.

  Examples of humectants include glycerin and sorbitol.

  The present invention also relates to the composition according to the invention as described above as a medicament.

  The invention also relates to the use of the composition according to the invention as described above in the pharmaceutical and cosmetic field.

  The compositions of the invention are particularly suitable for the treatment and / or prevention of hyperpigmentary disorders such as melasma, chloasma, lentigines, senile lentigo, vitiligo, freckles, post-inflammatory hyperpigmentations due to abrasion and / or burning and / or scarring and / or dermatitis and / or contact allergy; nevi, hyperpigmentations with genetic determinism, hyperpigmentations of metabolic or medicinal origin, melanomas or any other hyperpigmentary lesions. Preferably, the compositions according to the invention are particularly suitable for the treatment and / or prevention of melasma.

  The compositions according to the invention also find application in the cosmetics field, in particular in the protection against the harmful aspects of the sun, for preventing and / or for combating photoinduced or chronological aging of the skin and superficial body growths.

  The invention also relates to a non-therapeutic cosmetic treatment method for embellishing the skin and / or improving its surface appearance, characterized in that a composition is applied to the skin and / or its integuments. comprising 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid, an enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl) 2-naphthyl) 1-propynyl] benzoic acid.

  The invention also relates to a non-therapeutic cosmetic treatment method for embellishing the skin and / or improving its surface appearance, characterized in that a composition is applied to the skin and / or its integuments. comprising 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid, an enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl) 2-naphthyl) -1-propynyl] benzoic acid, and at least one depigmenting agent and / or at least one sunscreen.

  The examples of formulations below make it possible to illustrate the compositions according to the invention, without however limiting the scope thereof. Examples illustrating the depigmenting activity of the various compositions according to the invention are also described.

  In the compositions below (Examples 1 to 7), the proportions of the various constituents are expressed as percentage by weight relative to the total weight of the composition.

  Example 1: 0.10 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-35 tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl acid ] benzoic Steareth2 3.00 Steareth-21 2.00 Caprylic-capric triglyceride 4.00 Isohexadecane 5. 00 Cetearyl alcohol 1.00 Stearic acid 1.50 Sodium sulphite 0.20 Propylene glycol 8.00 Glycerin 2.00 Phenoxyethanol 1.00 Citric acid qs pH 5.5-6.0 Purified water Qs 100 This composition should be applied 2 times a day until total depigmentation for the treatment of lentigines.

  Example 2: 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid S (+) configuration 4-hydroxyanisol 4.00 Steareth-2 3.00 Steareth-21 2.00 Caprylic-capric triglyceride 4.00 Isohexadecane 5.00 Cetearyl alcohol 1.00 Stearic acid 1.50 Sodium sulphite 0.20 Propylene glycol 8.00 Glycerin 2.00 Phenoxyethanol 1.00 Citric acid qs pH 5.5-6.0 Purified water This composition should be applied twice a day until complete depigmentation for the treatment of lentigines.

  Example 3: 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid configuration R (-) Hydroquinone 2.00 Carbomer 0.10 Methyl Paraben 0.18 Propyl Paraben 0.02 Cetyl Alcohol 1.00 Stearic Acid 0.80 Caprylic Caprylic Triglyceride 1.50 Cyclomethicone 1.00 Mineral Oil 2.00 Propylene Glycol 5.00 Glycerin 2.00 Triethanolamine 5.00 Citric Acid qs pH 5.5-6.0 Purified Water Qsp 100 This composition should be applied once a day until complete depigmentation for the treatment of melasma. Example 4: 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-O, 10-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid configuration RIS Hydroquinone 4.00 Aluminum Magnesium Silicate 3.0010 Butyl Hydroxytoluene 0.04 Methyl Paraben 0.18 Propyl Paraben 0.02 Cetyl Alcohol 4.00 Stearic Acid 3.00 Stearyl Alcohol 4.00 Glyceryl Stearate / PEG-100 Stearate 3.50 Methyl Gluceth-10 5.00 Glycerin 4.00 Citric Acid 0.05 Metabisulfite of sodium 0.20 Purified water Qs 100 This composition should be applied twice a day until complete depigmentation for the treatment of melasma.

  Example 5: 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoate configuration S (+) Klucel HF 1.00 Propylene glycol 75.00 Ethanol 96 5.00 L-Lysine 50% 0.078 Purified water Qsp 100 This composition should be applied once a day until complete depigmentation for the treatment of lentigines. Example 6: 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-0.03-propynyl] benzoic acid S (+) configuration Klucel HF 1.00 Propylene glycol 75.00 Ethanol 96 5.00 L-Lysine 50% 0.0234 Purified water Qsp 100 This composition should be applied once a day until complete depigmentation for the treatment of lentigines. Example 7: 2-Hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid Lanette 16 2.00 Fluid DC 200 - 350 cSt 1.00 Arlacel 165 FL 5.00 Marcol 172 19.00 White Cerabeil 3.00 Nipasol M 0.05 Pemulen TRI NF 0.20 Methyl paraben 0.10 Dipropylene glycol care 15.00 Sodium hydroxide 0.1007 Purified water Qs 100 This composition should be be applied once a day until complete depigmentation for the treatment of lentigines.

  Example 8 Description: In this pilot study, the efficacy of 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl) 2-naphthyl) -1-propynyl] benzoic R or S configuration in the form of topical gel 0.03% or 0.01% was evaluated. A group of 48 patients with heliodermatitis of the hands took part in the study.

  Protocol: Randomized double-blind randomized intra-individual study. The treatment was applied once a day in the evening for ten weeks. The controls were performed at the start of the study at weeks 1, 5 and 10. The patients were divided into two clinical centers into three parallel groups. These groups being defined as: group 1: 0.01% gel versus vehicle; group 2: 0.03% gel versus vehicle and group 3: 0.01% gel versus 0.03% gel.

  Formulations: The formula of 0.01% gel corresponds to the formula of Example 5, the formula of 0.03% gel corresponds to the formula of Example 6, the vehicle corresponds to the formula of the example From which the asset was removed.

  Effectiveness measurement: The criteria used to evaluate the effectiveness of the gel were the hyperpigmentation score (Figure 1), the color of the target tasks (Figure 3), the surface of the target tasks (Figure 5), the criterion main assessment being the hyperpigmentation score.

  Estimation of the hyperpigmentation score: The hyperpigmentation score was measured using the L'Oréal 9-point image scale (registered model at L'Oréal). This scale is dichotomous for the scores of 4 and 5, in one case it is a hand with many small tasks, in the other case, it is a hand with some large tasks . The investigator thus compares the area to be examined with the photos (Figure 1) constituting the scale to give a score to each patient. The statistical analysis of scores is reported in Figure 2.

  Estimation of the color of the tasks: The measurement of the color of the pigmentary marks is done by means of a color chart graduated from 1 to 15 (figure 3) (Registered model - L'Oréal). The investigator compares the coloring of the tasks with the color chart to give a note to each patient. The statistical analysis of these is reported in Figure 4.

  Estimation of task size: A scale from 1 to 15 was used to measure task size (Figure 5). The investigator measures the size of the tasks present on the area to be examined using a perforated slide as shown in Figure 5. The statistical analysis of these measurements is reported in Figure 6.

  In conclusion, a significant superiority of 2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) ) -1-propynyl] benzoic compared to the vehicle as early as 5 weeks for the hyperpigmentation score. Similarly, the study of the size and color of pigmented spots also showed a marked improvement from 5 weeks for color and 10 weeks for size.

Claims (12)

claims   1. Depigmenting composition of the skin, comprising, in a physiologically acceptable medium, the acid   2-hydroxy-4- [3-hydroxy-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -1-propynyl] benzoic acid. 2. Composition according to claim 1, characterized in that it comprises an enantiomer or a mixture of enantiomers in all proportions of 2-hydroxy-4- [3-hydroxy-3- (5,6,7, 8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl-1-propynyl] benzoic acid.   3. depigmenting composition of the skin according to claim 1 or 2, characterized in that it also comprises at least one other depigmenting agent.   4. Composition according to claim 3, characterized in that the depigmenting agent is a phenol derivative.   5. Composition according to any one of claims 3 or 4, characterized in that the depigmenting agent is selected from hydroquinone and 4-hydroxyanisol.   6. Composition according to any one of claims 1 to 5, characterized in that it also comprises at least one sunscreen.   7. Composition according to any one of claims 1 to 6, characterized in that it further comprises at least one cosmetic or pharmaceutical additive.   8. A composition according to any one of claims 1 to 7 as a medicament. 30   9. Use of a composition according to any one of claims 1 to 7 for preparing a medicament for preventing and / or treating hyperpigmentary disorders selected from melasma, chloasma, lentigines, vitiligo, freckles post-inflammatory hyperpigmentations due to abrasion and / or burning and / or scarring and / or dermatitis and / or contact allergy; nevi, hyperpigmentations with genetic determinism, hyperpigmentations of metabolic or medicinal origin and melanomas.20   10. Use according to claim 9, characterized in that the medicament is intended for preventing and / or treating melasma.   11. Cosmetic use of a composition according to one of claims 1 to 7, for protection against the harmful aspects of the sun, for preventing and / or for combatting photo-induced or chronological aging of the skin and superficial body growths.   12. Non-therapeutic cosmetic treatment method for beautifying the skin and / or improving its surface appearance, characterized in that a composition is applied to the skin and / or its integuments. Claims 1 to 7.