FR2908308A1 - Cosmetic and/or dermatological composition, useful to fight against the cutaneous stress and for topical application, comprises active ingredient and carbonyl compound, in association/mixing with inert vehicle - Google Patents

Abstract

Cosmetic and/or dermatological composition for topical application, comprises an active ingredient and a carbonyl compound (I), in association or mixing with an inert vehicle, non toxic, adapted for topical application. Cosmetic and/or dermatological composition for topical application, comprises a active ingredient and a carbonyl compound (I) of formula (R1-C(=O)-N(-X)-(CH(R2))m-CH((CH2)p-OH)-(CH2)n-O-C(=O)-R3), in association or mixing with an inert vehicle, non toxic, adapted for topical application. X : H or 1-4C hydrocarbon chain; n, p : 0.1-2; m : 1-2; R1, R3 : 4-25C carbon chain containing 1-2 OH groups carried by different carbons; and R2 : H or 1-4C alkyl (optionally containing OH group). Provided that at least one of R1 and R2 is omega-3 fatty acid.

Description

1 Cosmetic and / or dermatological compositions containing a

  The present invention relates to the field of the necessities of life, and particularly to the cosmetic and / or dermatological domains. The present invention relates to cosmetic and / or dermatological compositions intended for topical application, containing a ceramide analog carrying at least one omega-3 polyunsaturated fatty acid chain. The invention more particularly relates to cosmetic and / or dermatological compositions intended for topical application, containing as active principle at least one compound corresponding to formula (I): ## STR2 ## wherein: m is an integer selected from the values 1 and 2; n and p are, independently of one another, integers selected from values 0, 1 and 2; -X is selected from hydrogen and a hydrocarbon chain having 1 to 4 carbon atoms; R1 and R3 are saturated or unsaturated carbon chains containing from 4 to 25 carbon atoms and optionally from 1 to 2 hydroxyl groups carried by distinct carbons, with the restriction that at least one of the R1 and R3 chains originates from A Omega-3 fatty acid; - R2 is chosen from hydrogen and an alkyl chain comprising from 1 to 4 carbon atoms, linear or branched, which may comprise a hydroxyl group, in combination or in admixture with an inert, non-toxic vehicle, suitable for topical application . The invention also relates to the use of these compositions for combating cutaneous stress. The behavior of a cell, particularly a cutaneous cell, is constantly monitored through the information it exchanges with its environment. It receives and transmits this information in the form of chemical or electrical signals at different concentrations. These signals allow him to regulate his activity and adapt to his environment.

  However, when they leave the physiological limits of the skin cell, it must manage a regulatory imbalance, called skin stress, in order to defend itself. This skin stress may be induced by psychological factors, but also physical or chemical, such as the friction of clothing or contact with aggressive substances. 10 A strong stress generated by different cells - including massively neurons, but also keratinocytes and mast cells - the release of CGRP (Calcitonin Gene-Related Peptide) and substance P. The inconveniences related to this release are more intense or less severe, ranging from a simple transient alteration of the skin condition to more serious skin conditions such as aggravation of pruritus, atopic dermatitis, certain urticaria and acne (PC ARCK, A. SLOMINSKI et al .: Neuroimmunology of stress: Skin Takes Center Stage, JID-126: 1697-1704 - August 2006.). In order to fight against stress, cosmetic or dermatological compositions intended for sensitive skin notably use inhibitors of CGRP of the peptide or antibody type, or in the form of a plant extract (US 6019967, WO 02/34230). . The polyunsaturated fatty acids and in particular the essential fatty acids (family of Omega-6 fatty acids and Omega-3 fatty acids) are essential molecules for the maintenance of the epidermal integrity, and are also recognized for their physiological properties. . Omega-3 fatty acids represent a family of molecules including in particular alpha-linolenic acid, as well as the fatty acids of fish oils such as EPA (eicosapentaenoic acid) or DHA (docosahexaenoic acid). Stearidonic acid (18: 4 n-3), less known, is also an Omega-3 fatty acid. The oral administration of omega-3 fatty acids has shown numerous beneficial effects for human physiology, especially in the prevention of cardiovascular problems (Dacosta Y. Omega-3 fatty acid supplementation - 1998), in the regulation of the anti-inflammatory response (Modulation of the Arachidonic Cascade with Omega-3 Fatty Acids or Analogues, Potential Therapeutic Benefits, Mini-Reviews in Medicinal Chemistry, 2004, 4, 659-668), in the maturation of the nervous system (Sinclair AJ 5 What is the yole of a-linolenic acid for mammals? 2002) and in the transduction of nerve signals (Omega-3 Fatty Acid - Anti-stress Conference - 2005). On the other hand, Omega-3 fatty acids are described as a means of reducing stress and its metabolic effects (Stress and Obesity, Clinical Nutrition and Metabolism, Nutr Clin, 10 Metab, 2006, vol 20, p. 99-107). However, it does not appear that an anti-stress effect of Omega-3 fatty acids has been demonstrated by topical administration. Ceramides are also compounds known for their role in maintaining skin integrity. They are present in many cosmetic compositions (EP1430871, EP1504747). Pharmaceutical compositions containing a ceramide or analog, conjugated to a protein, have been described to combat the effect of stress on cells (USP 5,939,390). However, these compositions are intended for oral or injection administration. It therefore does not appear that an anti-stress effect of ceramides or ceramide analogues has been demonstrated by topical administration. The present invention therefore relates to cosmetic and / or dermatological compositions intended for topical application, the active principle of which is a ceramide analog carrying at least one polyunsaturated fatty acid chain of Omega-3 type. The invention more particularly relates to cosmetic and / or dermatological compositions intended for topical application, containing as active principle at least one compound corresponding to formula (I): ## STR2 ## in which: m is a an integer selected from values 1 and 2; N and p are, independently of each other, integers selected from values 0, 1 and 2; X is chosen from hydrogen and a hydrocarbon chain containing from 1 to 4 carbon atoms; R 1 and R 3 are saturated or unsaturated carbon chains containing from 4 to 10 carbon atoms and optionally from 1 to 2 hydroxyl groups carried by distinct carbons, with the restriction that at least one of the chains R 1 and R 3 comes from an Omega-3 fatty acid; - R2 is chosen from hydrogen and an alkyl chain having 1 to 4 carbon atoms, linear or branched, and may include a hydroxyl group; The invention also relates to the use of these compositions for combating cutaneous stress. Indeed, the Applicant has demonstrated the effect of a ceramide analog carrying an Omega-3 type chain on the release of CGRP in cell cultures. Under stress conditions, the inhibition of the release of CGRP by an Omega-3 pseudo-ceramide has been noted (Example 2-2). The dose-dependent effect of this action has also been highlighted. The compounds of formula (I) may for example be synthesized according to the process described in patent application EP1644318. According to a preferred form of the invention, m is equal to 1. According to a preferred form of the invention, n is equal to 1. According to a preferred form of the invention, p is equal to 0 or 1. According to a preferred form of the invention, X is a hydrogen atom. According to a preferred form of the invention, R2 is a hydrogen atom. According to one preferred form of the invention, R 1 and / or R 3 are chosen from the chains of alpha-linolenic acid (18: 3 n-3), eicosapentaenoic acid (20: 5 n-3) of docosahexaenoic acid (22: 6 n-3) and stearidonic acid (18: 4 n-3). According to a preferred form of the invention, the content of the compositions of compounds of formula (I) ranges from 0.001 to 20% relative to the total weight of the composition. The compositions according to the invention are intended for topical application. They comprise an inert, non-toxic, cosmetically or dermatologically acceptable carrier, in combination or in admixture with the active ingredient. They may contain adjuvants commonly used in the cosmetics field, such as, for example, softening agents, gelling agents, antioxidants, solvents, filters, preserving agents, pigments or perfumes. The compositions according to the invention are in a form compatible with topical application, such as an aqueous, hydroalcoholic, hydroglycolic or oily solution, a dispersion, a suspension, an oil-in-water or water-in-oil emulsion, an aqueous gel or oily, cream, milk, ointment, lotion, paste, mousse or aerosol. The compositions according to the invention are intended for the fight against skin stress and its harmful effects on the skin. Without limitation, they may for example be used for one to two applications per day on the surface to be treated. EXAMPLES Example 1 Synthesis of a pseudo-ceramide derived from α-linolenic acid, of formula gal OO Step 1: amidification O 2 H 2 O 3, H 2 O OHOH Scheme 1 In a 2 L reactor 386.2 g (1.026 mol) of ethyl linolenate (II) and 91.1 g (1 mol) of 3-amino-1,2-propane diol (III) are introduced with a connection to a vacuum pump. ). 6.3 g of Novozym 435 (6.3 g for 1.026 mol of linoleic acid) are then added before heating the mixture to 65 ° C. under reduced pressure (50 mbar).

  After 20 hours of reaction, the product is filtered on a web of 250 m in order to remove the Novozym beads. The amide (IV) obtained is an orange-yellow solid and the conversion is> 99%.

In a 2 L reactor equipped with a connection to a vacuum pump, 351.5 g (1 mole) of linolenyl amide (IV) and 284 g (1 mole) of linolenyl amide (IV) are introduced. 5 g (1 mole) of ethyl hexadecanoate (V). 10 g of Lipozyme RM IM (10 g per 1 mole of linolenyl amide) are then added before heating the mixture to 65 ° C. under reduced pressure (50 mbar). After 5 hours of reaction, the reaction mixture is brought to 80 C.

After 24 hours of reaction, the product is filtered through a 50 m web to remove the enzyme particles. The pseudo-ceramide (Ia) obtained is an off-white waxy solid and the conversion obtained is 95%. This procedure is similar to the process described in patent application EP1644318 for analogous pseudo-ceramide derivatives. EXAMPLE 2 Effect of a pseudo-ceramide derivative of Omega-3 coupled to delipidated BSA on the electrophysiological activity of sensory neurons The product used is the compound of formula (Ia): ## EQU1 ## The product is not not soluble in aqueous media, and therefore in culture media. It was therefore vectorized with BSA (Bovine Serum Albumin) delipidated. Cellular model: culture of sensory neurons from dorsal spinal ganglia of 15-day-old rat embryos. The following non-cytotoxic concentrations were retained: 1% BSA +/- 0.1%; 0.03%; 0.01% Omega-3 pseudo-ceramide of formula (Ia). Example 2-1: Stress-free Conditions The influence of the products on the basal CGRP release rate was studied without a stress inducer. Conduct of the test: Culture of neurons for 10 days (at 37 C, 5% humidity) in 96-well plates; Incubation of the cells for 24 h and 48 h with the products under test; Assay of released CGRP in supernatants by sandwich ELISA. Results: Given the vectorization in the presence of BSA, we compared: The effect of the BSA alone compared to the untreated control • The effect of the product compared to the BSA and compared to the untreated control 8 5 Table I: Capsaicin-free test - 24 h CGRP Mean +/-% inhibition% inhibition (pg / mL) standard deviation compared to control BSA _ 332.5 Untreated control 277.8 - - 352.6 309.8 +/- 21.7 345.6 240.6 Witness 1% BSA 53.6 63.7 - 57.5 53.1 +/- 3.6 -83% 45.4 45, 2 Omega-3 + 1% BSA 227.4 0.1% Omega-3 219.9 288.2 200.8 +/- 29.7 -35% + 278% 130.4 138.1 0.03% Omega -3,154.6 196.3 230.0 174.5 + / • - 18.3 -44% + 229% 122.6 168.9 0.01% Omega-3 104.1 143.9 111.9 106 , 3 +/- 10.7-66% + 100% 84.3 87.3 Table II: Test without Capsaicin - 48 h CGRP Mean +/-% inhibition% inhibition (pg / mL) standard deviation relative to the control BSA Control untreated 276.6 323.4 316.8 307.8 +/- 8.2 - - 314.6 307.7 Control 1% BSA 38.3 50.1 42 , 0 43.1 +/- 1.9 -86% - 9 15 2908308 10 42.0 43.2 Omega-3 + 1% BSA 0.1% Omega-3 121.3 163.5 143.5 + - 12.5 -53% + 233% 159.0 167.7 106.0 0.03% Omega-3 86.8 77.4 68.1 75.1 +/- 4.3 -76% + 74% 62.9 80.4 0.01% Omega-3 58, 2 75.5 76.0 70.4 + 1- 3.3 -77% + 64% 73.3 69.3 Under stress-free conditions, the Omega-3 pseudo-ceramide attenuates the inhibition of spontaneous and basal release of CGRP by BSA. It thus restores the basal dialogue of neurons with their environment. Example 2-2: Stress Conditions The stress conditions were implemented by treatment with Capsaicin at 10 -6 M.

Run of the test: Culture of neurons for 10 days (at 37 ° C., 5% humidity) in 96-well plates; Incubation of the cells for 24 and 48h with the products under test; After this incubation, treatment with 10 "M capsaicin for 20 minutes, assay of the CGRP released in the supernatants by a sandwich ELISA test Results: Given the vectorization in the presence of BSA, we compared The effect of BSA alone compared to the untreated control The effect of the product with respect to BSA and with respect to the untreated control Table III: Capsaicin test 24 h All wells are treated with Capsaicin - untreated means no product (1a) CGRP Mean + 1% inhibition% inhibition (pg / mL) standard deviation from control BSA control untreated 734.4 728, 9,731.8,750.6 +, / - 11.6 - - 779.3 778.8 Indicator 1% BSA 758.6 740.2 739.2 758.4 +/- 8.4 0% - 780.5 773.4 Omega-3 + 1% BSA 0.1% Omega-3 623.7 595.2 586.6 +/- 10.4 -22% -23% 567.1 573.5 573.7 0.03 % Omega-3 651.2 602, 4629.5 653.0 +/- 19.7 -13% -14% 661.2 720.9 0.01% Omega-3 718.5 699.4 724, 7 725.8 +/- 9.5 -3% -4% 728, Table IV: Capsaicin test - 48 h CGRP Mean +/-% inhibition% inhibition (pg / mL) standard deviation compared to control BSA _ 567.0 Control no treated 560.8 561.5 563.3 +/- 1.1 - - 564.3 562.8 Witness 1% BSA 558.1 563, 5 565.7 563.6 +/- 4.6 0% - 579 , 0 551.4 Omega-3 + 1% BSA 255.9 0.1% Omega-3 326.9 327.4 263.3 +/- 27.8 -53% -53% 198.0 208.3 0 , 03% Omega-3 233.2 192, 6 218.2 204.8 + 1- 9.4 -64% -64% 180.0 200.2 0.01% Omega-3 340.4 368.8 382 , 1 345.4 + 1- 13.6 -39% -39% 305.9 329.8 Under stress conditions, Omega-3 pseudo-ceramide inhibits, in a dose-dependent manner, the harmful release of CGRP .

EXAMPLE 3 Cosmetic compositions containing omega-3 pseudo-ceramides of formula (I): Example 3-1: Mattifying cream gel: Ingredients Nomenclature INCI% PHASE A (mass) Water 1 Aqua qsp Allantoin [Allantoin 0.20 Preservative Butylene glycol 2.00; Butylene glycol Polyacrylate 13 / Polyisobutene / Polyacrylate 13 / Polyisobutene / Polysorbate 1.50 Polysorbate 20 20 PHASE B Pseudo-ceramide Omega-3 1 0.20 Diisopropyl adipate Diisopropyl adipate 3.00 PHASE C Isopropyl palmitate Isopropyl palmitate 4.00 Cyclopentasiloxane / Cyclopentasiloxane polymer / Dimethicone 6.00 dirnethicone crosspolymer ___ PHASE D Sebustop (Solabia) Butylene glycol / Aqua / Cinnamomum cassia 3.00 / Zingiber officinale / Poterium officinale Fragrance 0.20 DC Yellow 6 (LCW) CI 15985 0.70 Example 3-2: Soothing cream: Ingredients Nomenclature INCI% (mass) PHASE A Methyl glucose sesquistearate Methyl glucose sesquistearate 4.00 Behenyl alcohol 2. Behenyl alcohol 2. Butylene glycol dicaprylate / dicaprate 4.00 Dicaprylate / butylene glycol dicaprate Dimethicone Dimethicone 2.

00 Octyldodecanol Octyldodecanol 4.00 Omega-3 pseudo-ceramide _ 1.00 PHASE B Aqua water qs 100 Glycerine ù Glycerin __..__.... 2. Xanthan gum Xanthan gum 0.30 PHASE C Biosaccharide gum Biosaccharide gum-2 5.00 2908308 14 Cyclopentasiloxane / dimethicono_l Cyclopentasiloxane / dimethiconol 1.50 Sepigel 305 (Seppic) Polyacrylamide / C13-14 isoparaffin / 1.00 Laureth-7 ~ _ Fragrance 0.20 Preservative qs Example 3-3: Shampoo: Ingredients Nomenclature INCI% (mass) PHASE A _ Aqua water qs 100 Preservative qs Xanthan gum Xanthan gum 0.10 Copolymer acrylate __ __ Acrylates copolymer _. _. 6.00 PHASE B Plantapon 611C (Cognis) Sodium laureth sulfate / cocamidopropyl 25.00 betaine / coco glucoside _ Glycol distearate / laureth-4 / 2.50 Tego pearl N300 (Cochamidopropyl Betaine Degussa Goldschmidt) PHASE C Sodium Hydroxide, 10% solution 1.00 PHASE D Nickname Omega-3-Ceramide 0.20 Cocamide DEA Cocamide DEA 1.50 PHASE E Nogaline (Solabia) Butylene glycol / Aqua / Juglans regia 2.00 Zinc pyrrolidone carboxylate Zinc PCA 0.15 5

Claims (10)

  Cosmetic and / or dermatological compositions intended for topical application, characterized in that they contain, as active principle, at least one compound corresponding to formula (I): ## STR2 ## p wherein: m is an integer selected from the values 1 and 2; N and p are, independently of one another, integers selected from 0, 1 and 2; X is chosen from hydrogen and a hydrocarbon chain containing from 1 to 4 carbon atoms; R1 and R3 are saturated or unsaturated carbon chains containing from 4 to 25 carbon atoms and optionally from 1 to 2 hydroxyl groups carried by distinct carbons, with the restriction that at least one of the chains R1 and R3 comes from an Omega-3 fatty acid; R2 is chosen from hydrogen and an alkyl chain comprising from 1 to 4 carbon atoms, linear or branched, which may comprise a hydroxyl group, in combination or in admixture with an inert, non-toxic vehicle, adapted to the application; topical.   2. Compositions according to claim 1, wherein at least one of the groups R1 and R3 is selected from the chains of alpha-linolenic acid (18: 3 n-3), eicosapentaenoic acid (20: N-3) docosahexaenoic acid (22: 6 n-3) and stearidonic acid (18: 4 n-3).   3. Compositions according to claim 1 or claim 2, such that in the formula (I), m is equal to 1.   4. Compositions according to one of the preceding claims, such that in the formula (I), n is equal to 1. 30 2908308 16   5. Compositions according to one of the preceding claims, such that in formula (I), p is equal to 0 or 1.   6. Compositions according to one of the preceding claims, such that in formula (I), X is a hydrogen atom.   7. Compositions according to one of the preceding claims, such that in formula (I), R2 is a hydrogen atom.   8. Compositions according to claim 1, characterized in that they contain as active principle, at least one compound corresponding to the formula (Ia):   9. Compositions according to one of the preceding claims, such that their content of compound of formula (I) ranges from 0.001 to 20% relative to the total weight of the composition.   10. Cosmetic use of the compositions according to one of the preceding claims, to fight against skin stress by topical application. 20