USE OF ESTERS OF N-ACYLATED DERIVATIVES OF AMINO ACIDS AND POLYOLS AS AN ANTI-AGEING AGENT FOR HUMAN SKIN

Abstract

Disclosed is a compound of formula (I′): R′—O—CH2-CH(OH)—[CH2-O—CH2]s-[CH(OH)]p-CH2-O—R″ (I′), formula (I″), wherein s is equal to 0 or 1, and p is equal to 0, 1, 2 or 3, R′ and R″, identical or different, represent a hydrogen atom, or a monovalent radical of formula (II′a), or a monovalent radical of formula (II′b), in order to prevent or slow down the appearance of the signs of ageing of the human skin or lips or to eradicate these signs. Also disclosed are a novel product, novel composition and cosmetic method.

Claims

1. A method for preventing or slowing the appearance of signs of aging of human skin or the lips or else of eliminating said signs, the method comprising providing and applying an effective amount of a compound of formula (I′):
R′—O—CH.sub.2—CH(OH)—[CH.sub.2—O—CH.sub.2].sub.s—[CH(OH)].sub.p—CH.sub.2—O—R″  (I′), in which formula (I′) s is equal to 0 or to 1, and p is equal to 0, 1, 2 or 3, R′ and R″, which may be identical or different, represent either a hydrogen atom, or a monovalent radical of formula (II′a): ##STR00009## in which formula (II′a) the group R1-C(═O)— represents a radical chosen from the octanoyl, decanoyl, ω-undecylenoyl, dodecanoyl, tetradecanoyl, hexadecanoyl, octadecanoyl, cocoyl, eicosanoyl, 9-octadecenoyl, eicosenoyl, 9,12-octadecadienoyl or 9,12,15-octadecatrienoyl radicals, R2 represents a hydrogen atom or a radical chosen from the methyl, isopropyl, isobutyl, 1-methylpropyl, hydroxymethyl, 1-hydroxyethyl, 4-aminobutyl, 3-guanidinopropyl, 3-ureidopropyl, (1-aminocarbonyl)methyl, carboxymethyl, 2-carboxyethyl, 2-(aminocarbonyl)ethyl, benzyl, 4-hydroxybenzyl, 3,4-dihydroxybenzyl, [1H-indol-3-yl]methyl, (1H-imidazol-4-yl)methyl, 3-aminopropyl radicals, and R3 represents a hydrogen atom or a methyl radical; or a monovalent radical of formula (II′b): ##STR00010## in which formula (II′b) the group R1-C(═O)— represents a radical chosen from radicals represents a radical chosen from the octanoyl, decanoyl, ω-undecylenoyl, dodecanoyl, tetradecanoyl, hexadecanoyl, octadecanoyl, cocoyl, eicosanoyl, 9-octadecenoyl, eicosenoyl, 9,12-octadecadienoyl or 9,12,15-octadecatrienoyl radicals and R4 represents a hydrogen atom or a hydroxy radical, it being understood: that at least one of the radicals R′ and R″ does not represent a hydrogen atom, that, when neither of the radicals R′ and R″ represents a hydrogen atom, R′ and R″ are identical but do not represent a monovalent radical of formula (II′a) in which the group R1-C(═O) represents the ω-undecylenoyl radical, R2 represents a benzyl radical and R3 represents a hydrogen atom and that when one of the radicals R′ and R″ represents a hydrogen atom, the other does not represent a monovalent radical of formula (II′a) in which the group R1-C(═O) represents the ω-undecylenoyl radical, R2 represents a benzyl radical and R3 represents a hydrogen atom.

2. The method as defined in claim 1, of a composition (C′1) comprising, per 100% of its mass: from 99% by mass to 20% by mass of at least one compound of formula (I′a):
R′—O—CH.sub.2—CH(OH)—[CH.sub.2—O—CH.sub.2].sub.s—[CH(OH)].sub.p—CH.sub.2—O—H  (I′a), formula (I′a) corresponding to the formula (I′) as defined previously in which R″ represents a hydrogen atom, from 1% by mass to 80% by mass of at least one compound of formula (I′b):
R′—O—CH.sub.2—CH(OH)—[CH.sub.2—O—CH.sub.2].sub.s—[CH(OH)].sub.p—CH.sub.2—O—R  (Ib), formula (Ib) corresponding to the formula (I′) as defined previously in which R′ and R″ are identical and represented by the radical R.

3. The method as defined in claim 1, wherein, in the formula (II′a), R2 represents a radical chosen from the methyl, isopropyl, isobutyl, 1-methylpropyl or benzyl radicals and wherein, in the formula (II′b), R4 represents a hydrogen atom.

4. The method as defined in claim 1, for which, in the formulae (I′), (I′a) or (I′b), either s and p are equal to 0 or else s and p are equal to 1.

5. A process for the purpose of preventing or slowing the appearance of signs of aging of human skin or the lips, or else of eliminating said signs, comprising at least one step of applying to human skin or to the lips a cosmetic formulation for topical use comprising at least one cosmetically acceptable excipient and an effective amount of the compound of formula (I′), as defined in claim 1.

6. A process for the purpose of preventing or slowing the appearance of signs of aging of human skin or the lips, or else of eliminating said signs, comprising at least one step of applying to human skin or to the lips a cosmetic formulation for topical use comprising at least one cosmetically acceptable excipient and an effective amount of composition (C′1) as defined in claim 2.

7. A compound of formula (I″), corresponding to the formula (I′) as defined in claim 1, wherein: when neither of the radicals R′ and R″ represents a hydrogen atom and when R′ and R″ are identical, they do not represent a monovalent radical of formula (II′a) either in which the group R1-C(═O) represents the tetradecanoyl radical, R2 represents a benzyl radical and R3 represents a hydrogen atom and that; when one of the radicals R′ and R″ represents a hydrogen atom, the other does not represent a monovalent radical of formula (II′a) either in which the group R1-C(═O) represents the tetradecanoyl radical, R2 represents a benzyl radical and R3 represents a hydrogen atom.

8. The compound of formula (I″) as defined in claim 7, for which: in the definition of the monovalent radical of formula (II′a), the group R1-(C═O) and R3 are as defined previously and R2 represents a radical chosen from the methyl, isopropyl, isobutyl, 1-methylpropyl or benzyl radicals and in the definition of the monovalent radical of formula (II′b), the group R1-(C═O) is as defined previously and R4 represents a hydrogen atom.

9. The compound of formula (I″) as defined in claim 7, in which either s and p are equal to 0 or else s and p are equal to 1.

10. A composition (C″1) comprising, per 100% of its mass: from 99% by mass to 20% by mass of at least one compound of formula (I″a):
R′—O—CH.sub.2—CH(OH)—[CH.sub.2—O—CH.sub.2].sub.s—[CH(OH)].sub.p—CH.sub.2—O—H  (I″a), formula (I″ a) corresponding to the formula (I″) as defined in claim 7, in which R″ represents a hydrogen atom, from 1% by mass to 80% by mass of at least one compound of formula (I″b):
R—O—CH.sub.2—CH(OH)—[CH.sub.2—O—CH.sub.2].sub.s—[CH(OH)].sub.p—CH.sub.2—O—R  (I″b), formula (I″ b) corresponding to the formula (I″) as defined in claim 7, in which R′ and R″ are identical and represented by the radical R.

11. The composition (C″1) as defined in claim 10 for which: in the definition of the monovalent radical of formula (II′a), the group R1-(C═O) and R3 are as defined previously and R2 represents a radical chosen from the methyl, isopropyl, isobutyl, 1-methylpropyle or benzyl radicals and, in the definition of the monovalent radical of formula (II′b), the group R1-(C═O) is as defined previously and R4 represents a hydrogen atom.

12. The composition (C″1) as defined in claim 9, for which, in the formulae (I″ a) and (I″ b), either s and p are equal to 0 or else s and p are equal to 1.

13. A cosmetic formulation for topical use, further comprising at least one cosmetically acceptable excipient and an effective amount of the compound of formula (I″) as defined in claim 7.

14. A process for the purpose of preventing or slowing the appearance of signs of aging of human skin or the lips, or else of eliminating said signs, comprising at least one step of applying to human skin or to the lips a cosmetic formulation for topical use comprising at least one cosmetically acceptable excipient and an effective amount of at least one compound of formula (I″) as defined in one or claim 7.

15. The method as defined in claim 2, wherein, in the formula (II′a), R2 represents a radical chosen from the methyl, isopropyl, isobutyl, 1-methylpropyl or benzyl radicals and wherein, in the formula (II′b), R4 represents a hydrogen atom.

16. The method as defined in claim 2, for which, in the formulae (I′), (I′a) or (I′b), either s and p are equal to 0 or else s and p are equal to 1.

17. The method as defined in claim 3, for which, in the formulae (I′), (I′a) or (I′b), either s and p are equal to 0 or else s and p are equal to 1.

18. The compound of formula (I″) as defined in claim 8, in which either s and p are equal to 0 or else s and p are equal to 1.

19. The composition (C″1) as defined in claim 10, for which, in the formulae (I″ a) and (I″ b), either s and p are equal to 0 or else s and p are equal to 1.

20. A cosmetic formulation for topical use, further comprising at least one cosmetically acceptable excipient and an effective amount of the compound of formula (I″) as defined in claim 8.

Description

EXAMPLE 1: PREPARATION OF A COMPOSITION (C1.SUB.A.) ACCORDING TO THE INVENTION

[0107] 500 g of alanine, i.e. 1 molar equivalent, are introduced into an aqueous-alcoholic mixture consisting of 1800 g of water and 200 g of isopropanol at a temperature of 20° C. The pH of the medium is adjusted to 10 by adding 30% sodium hydroxide solution. 731.7 g of octanoyl chloride, i.e. 0.8 molar equivalent, are then gradually added to the mixture maintained between 20° C. and 50° C. and at a pH of between 10 and 10.5.

[0108] The reaction medium is then kept stirring for 2 hours and then heated to reach 70° C., followed by addition of 979.6 g of an acidic solution of 75% phosphoric acid to gradually reach a pH value equal to 2.0. The aqueous phase of the medium is separated out by settling and the organic phase remaining in the reactor is washed several times with brine at room temperature with stirring. On conclusion of washing and then drying by distillation under vacuum of the residual water, the organic phase comprising 922.3 g of the desired N-octanoyl alanine is obtained.

[0109] 59.2 g of glycerol, i.e. 1 molar equivalent of glycerol, are introduced with stirring into the reactor comprising a fraction of the preceding organic phase, which contains 0.8 molar equivalent of N-octanoyl alanine. The temperature is brought to 120° C., 0.44 g of 98% sulfuric acid and 0.44 g of 50% hypophosphorous acid are then added and the resulting mixture is brought to 125° C. under partial vacuum while sparging with nitrogen. The reaction mixture is then kept stirring for 12 hours at this temperature, and then neutralized by adding 30% sodium hydroxide solution so as to obtain a pH of composition (C1.sub.A), diluted to 5% in water, of between 3.0 and 6.0.

[0110] The analytical characteristics of composition (C1.sub.A) obtained are as follows:

Acid number (according to NFT 60-204)=16.8 pH 5% of composition (C1.sub.A) in water (according to method NFT 73-206)=4.5
Hydroxyl number (according to U.S. Pharmacopea XXI NF XVI 01/011985)=284.0
Ester number (calculated by the difference between the saponification number measured according to method NFT 60-110 and the acid number measured according to method NFT 60-204)=196.2
Saponification number (according to NFT 60-206)=213.0 mg KOH/g

EXAMPLE 2: PREPARATION OF A COMPOSITION (C1.SUB.B.) ACCORDING TO THE INVENTION

[0111] The procedure of the process described in Example 1 is performed, replacing the molar equivalent of alanine with a molar equivalent of leucine to obtain composition (C1.sub.B), the analytical characteristics of which are as follows:

Acid number (according to NFT 60-204)=13.7 pH 5% of composition (C1.sub.B) in water (according to method NFT 73-206)=5.5
Hydroxyl number (according to U.S. Pharmacopea XXI NF XVI 01/011985)=316.9
Ester number (calculated by the difference between the saponification number measured according to method NFT 60-110 and the acid number measured according to method NFT 60-204)=164.9
Saponification number (according to NFT 60-206)=178.6 mg KOH/g

EXAMPLE 3: PREPARATION OF A COMPOSITION (C1.SUB.C.) ACCORDING TO THE INVENTION

[0112] The procedure of the process described in Example 1 is performed, replacing the molar equivalent of alanine with a molar equivalent of leucine and the 0.8 molar equivalent of octanoyl chloride with 0.8 molar equivalent of hexadecanoyl chloride to obtain composition (C1.sub.C), the analytical characteristics of which are as follows:

Acid number (according to NFT 60-204)=12.2
pH 5% of composition (C1.sub.c) in water (according to method NFT 73-206)=6.4
Hydroxyl number (according to U.S. Pharmacopea XXI NF XVI 01/011985)=150.7
Ester number (calculated by the difference between the saponification number measured according to method NFT 60-110 and the acid number measured according to method NFT 60-204)=132.5
Saponification number (according to NFT 60-206)=144.7 mg KOH/g

EXAMPLE 4: PREPARATION OF A COMPOSITION (C1.SUB.D.) ACCORDING TO THE INVENTION

[0113] The procedure of the process described in Example 1 is performed, replacing the molar equivalent of alanine with a molar equivalent of isoleucine, to obtain composition (C1.sub.D), the analytical characteristics of which are as follows:

Acid number (according to NFT 60-204)=44.8
pH 5% of composition (C1.sub.D) in water (according to method NFT 73-206)=5.1
Hydroxyl number (according to U.S. Pharmacopea XXI NF XVI 01/011985)=364.7
Ester number (calculated by the difference between the saponification number measured according to method NFT 60-110 and the acid number measured according to method NFT 60-204)=142.9
Saponification number (according to NFT 60-206)=187.7 mg KOH/g

EXAMPLE 5: PREPARATION OF A COMPOSITION (C1.SUB.E.) ACCORDING TO THE INVENTION

[0114] The procedure of the process described in Example 1 is performed, replacing the molar equivalent of alanine with a molar equivalent of phenylalanine and the 0.8 molar equivalent of octanoyl chloride with 0.8 molar equivalent of hexadecanoyl chloride, to obtain composition (C1.sub.E), the analytical characteristics of which are as follows:

Acid number (according to NFT 60-204)=12.4
pH 5% of composition (C1.sub.E) in water (according to method NFT 73-206)=6.0
Hydroxyl number (according to U.S. Pharmacopea XXI NF XVI 01/011985)=230.1
Ester number (calculated by the difference between the saponification number measured according to method NFT 60-110 and the acid number measured according to method NFT 60-204)=112.9
Saponification number (according to NFT 60-206)=125.3 mg KOH/g

EXAMPLE 6: PREPARATION OF A COMPOSITION (C1.SUB.F.) ACCORDING TO THE INVENTION

[0115] The procedure of the process described in Example 1 is performed, replacing the molar equivalent of alanine with a molar equivalent of proline and the 0.8 molar equivalent of octanoyl chloride with 0.8 molar equivalent of cocoyl chloride, to obtain composition (C1.sub.F), the analytical characteristics of which are as follows:

Acid number (according to NFT 60-204)=28.7
pH 5% of composition (C1.sub.E) in water (according to method NFT 73-206)=5.1
Hydroxyl number (according to U.S. Pharmacopea XXI NF XVI 01/011985)=283.6
Ester number (calculated by the difference between the saponification number measured according to method NFT 60-110 and the acid number measured according to method NFT 60-204)=138.0
Saponification number (according to NFT 60-206)=166.7 mg KOH/g

Demonstration of the Antiaging Activity of the Compounds and Compositions According to the Invention Via an In Vitro Study of Migration of Human Fibroblasts.

[0116] Demonstration of the antiaging activity of the compositions according to the invention was performed by using a study model consisting in studying the migratory capacity of normal human fibroblasts not treated or treated with the compositions according to the invention and references. The fibroblast migration test is a test commonly used in the cosmetics and pharmaceutical sector and is especially described in the international patent application published under the number WO 2010/056908 A1. It allows in vitro reproduction of the phenomenon of fibroblast migration; a decrease in the migratory capacities of the fibroblasts being reported as associated with aging of the skin (1) (4).

Protocol:

[0117] Normal human fibroblasts at the R5 passage were amplified in a T75 culture flask and then inoculated at 25 000 cells/well in specific culture plates. These plates are dedicated to migration (Oris™ from Platypus), integrating a central zone without initial deposition of cells (stoppers). After 96 hours of plate amplification and 2 hours before the treatment, all the wells were treated with mitomycin C (2 hours at 10 pg/ml), so as to stop the cell proliferation, and thus to observe only the migration phenomenon. The stoppers were removed, and the references, the products or standard medium for fibroblasts containing 2% fetal calf serum (FCS) were applied to the cells under 100 μl, and then incubated for 40 hours at 37° C. under 5% CO.sub.2. Each condition was performed in quadruplicate.

Evaluation of the Effects:

[0118] On conclusion of the incubation, the cells were labeled with Calcein AM (5 μM, 20 minutes at 37° C.), so as to visualize the viable cells by fluorescence (revelation of the cytoplasm). Photos were taken, after having inserted a black screen under the culture plates, so as to visualize only the zone where the cells were not deposited. Thus, only the cells which had migrated were photographed (×4 objective lens; with a ×0.7 reducer on the camera adapter). The mean migration distance of the cells (D.sub.migr) was measured with NIS-Elements-BR 3.0 (4 cells). The means and standard deviations of the distances were calculated on the quadruplicates. The percentages of migratory effect relative to the control, and also the statistics (Student test) were also calculated.

Results:

[0119] The results obtained are collated in Table 1 below:

TABLE-US-00001 TABLE 1 Migration of fibroblasts in the presence of the test compositions [(D.sub.migr) − (D.sub.migr).sub.control]/ Test products (w/v) (D.sub.migr) in μm (D.sub.migr).sub.control FCS culture control (20 mg/ml) 168 ± 34 Epidermal Growth Factor (EGF) 203 ± 20 +21% 10 ng/ml Epidermal Growth Factor (EGF) 212 ± 8  +26% 50 ng/ml Composition (C1.sub.A) (5 μg/ml) 203 ± 34 +21% Composition (C1.sub.A) (10 μg/ml) 198 ± 23 +18% Composition (C1.sub.B) (5 μg/ml) 185 ± 17 +10% Composition (C1.sub.C) (5 μg/ml) 190 ± 6  +13% Composition (C1.sub.C) (10 μg/ml) 185 ± 3  +10% Composition (C1.sub.D) (10 μg/ml) 181 ± 7   +8% Composition (C1.sub.E) (5 μg/ml) 192 ± 9  +14% Composition (C1.sub.F) (5 μg/ml) 195 ± 6  +16%

[0120] The combination of EGF at 10 and 50 ng/ml with the normal human fibroblasts show an increase in the migration distance of said fibroblasts, thus validating the chosen model. The combination of compositions (C1.sub.A), (C1.sub.E), (C1.sub.D), (CI.sub.D), (C1.sub.E) and (C1.sub.F) with the normal human fibroblasts show a significant increase in the migration distance of said fibroblasts, and consequently an improvement in the migratory properties of the fibroblasts of human skin dermis, thus constituting an effective means for preventing and/or treating aging of the skin of the human body and the lips.

BIBLIOGRAPHY

[0121] (1): Schulze et al., “Stiffening of human skin fibroblasts with age”; Clin. Plast. Surg.; 2012; 39(1):9-20. [0122] (2): Baraibar and Friguet, “Oxidative proteome modifications target specific cellular pathways during oxidative stress, cellular senescence and ageing”; Exp Gerontol; 2013; 48(7):620-5. [0123] (3): Kondo et al., “Inhibitory effects of human serum on human fetal skin fibroblast migration: migration-inhibitory activity and substances in serum, and its age-related changes”; In Vitro Cell Dev Biol Anim; 2000; 36(4):256-61. [0124] (4): Jang et al., Prolonged activation of ERK contributes to the photorejuvenation effect in photodynamis therapy in human dermal fibroblasts; JID; 2013; 133(9):2265-75. [0125] (5): Houreld and Abrahamse “Low-intensity laser irradiation stimulates wound healing in diabetic wounded fibroblast cells (WS1)”, 2010, Diabetes Technol Ther, December;12(12) [0126] (6): Tang et al., “A rice-derived recombinant human lactoferrin stimulates fibroblast proliferation, migration, and sustains cell survival”, 2010, Wound Repair Regen, January-February 18(1) [0127] (7): Demirovic and Rattan, “Curcumin induces stress response and hormetically modulates wound healing ability of human skin fibroblasts undergoing ageing in vitro”, 2011, Biogerontology, March 6 [0128] (8): Rojo et al., “Wound healing properties of nut oil from Pouteria lucuma”, 2010, J Cosmet Dermatol, September 9(3)