NOVEL 1-PHENYLMONO- OR -POLYHYDROXYPROPANE COMPOUNDS, COMPOSITIONS AND COSMETIC USES THEREOF

Abstract

The present invention relates to novel compounds of formula (I)

##STR00001##

to compositions comprising same, and also to the use thereof for preventing and/or cosmetically treating the signs of aging of the skin.

Claims

1. A process for preventing and/or reducing the signs of aging of the skin which comprises applying to the skin a compound of formula (I) ##STR00034## in which n=0; 1; 2 or 3 m=0; 1; 2 or 3 with 1≦m+n≦3 R1 independently denotes a linear C1-C6 alkyl radical or a branched C3-C6 alkyl radical or a linear C1-C6 acyl radical, R2 and R3 independently denote a hydrogen atom or an OH radical, an optical isomer, stereoisomer and/or diastereoisomer thereof and/or salts thereof, provided that when R1 denotes methyl, R2 denotes a OH radical, and R3 denotes a hydrogen atom then 2≦m+n≦3.

2. A process for preventing and/or reducing the signs of aging of the skin which comprises applying to the skin a compound of formula (I) ##STR00035## in which n=0; 1; 2 or 3 m=0; 1; 2 or 3 with 2≦m+n≦3 R1 independently denotes a linear C1-C6 alkyl radical or a branched C3-C6 alkyl radical or a linear C1-C6 acyl radical, R2 and R3 independently denote a hydrogen atom or an OH radical, and also an optical isomer, stereoisomer and/or diastereoisomer thereof and/or salts thereof.

3. The process as claimed in claim 1, wherein, in the compound of formula (I): n=0; 1; 2 or 3 m=0; 1; 2 or 3 with 2≦m+n≦3 each of the substituents R1 independently denotes a linear C1-C4 alkyl radical; R2 and R3 independently denote a hydrogen atom or a hydroxyl radical.

4. The process as claimed in claim 1, wherein the compound of formula (I) is a compound of formula (II): ##STR00036## in which: n=0; 1; 2 or 3 m=0; 1; 2 or 3 with 2≦m+n≦3 each of the substituents R1 independently denotes a linear C1-C6 alkyl radical or a branched C3-C6 alkyl radical or a linear C1-C6 acyl radical, R2 denotes a hydrogen atom or a hydroxyl radical.

5. The process as claimed in claim 4, in which: n=0; 1; 2 or 3 m=0; 1; 2 or 3 with 2≦m+n≦3 each of the substituents R1 independently denotes a linear C1-C4 alkyl radical, preferably denotes methyl; R2 denotes a hydrogen atom or a hydroxyl radical.

6. The process as claimed in claim 1, wherein the compound of formula (I) is chosen from compounds 1 to 4 and 7 below, the optical isomers, stereoisomers and diastereoisomers thereof and/or geometrical isomers thereof and/or salts thereof: TABLE-US-00005 Compound Structure 1   2 3 4 7

7. The process as claimed in claim 1, wherein the compound of formula (I) is a compound of formula (III): ##STR00042## in which: n=0; 1; 2 or 3 m=0; 1; 2 or 3 with 1≦m+n≦3 each of the substituents R1 independently denotes a linear C1-C6 alkyl radical or a branched C3-C6 alkyl radical or a linear C2-C6 acyl radical.

8. The process as claimed in claim 1, wherein the compound of formula (I) is chosen from compounds 5 and 6 below, the optical isomers, stereoisomers and diastereoisomers thereof or geometrical isomers thereof and/or salts thereof: TABLE-US-00006 Compound Structure 5   6

9. The process as claimed in claim 1, wherein the compound of formula (I) is present, in a composition containing a physiologically acceptable medium, at a concentration of between 0.0001% and 40% by weight relative to the total weight of the composition.

10. The process according to claim 1 which is a cosmetic treatment process for reducing or preventing the signs of aging of mature and/or wrinkled skin, characterized in that a compound of formula (I) or a composition containing it, is applied to the mature and/or wrinkled skin.

11. The cosmetic treatment process as claimed in claim 10, wherein it is intended for promoting the renewal of the keratinocytes and for reducing or preventing signs chosen from thinning of the epidermis, surface wrinkles and impairment of the barrier function.

12. A compound of formulae (V) to (IX): Formula (V): ##STR00045## in which: n=1 or 2 each of the substituents R1 independently denotes a hydrogen atom or a linear C1-C6 alkyl or a branched C3-C6 alkyl Formula (VI): ##STR00046## in which: when R2 denotes a hydroxyl radical, then R3 denotes a hydrogen atom, when R2 denotes a hydrogen atom, then R3 denotes a hydroxyl radical, each of the substituents R1 independently denotes a hydrogen atom or a linear C1-C6 alkyl or a branched C3-C6 alkyl ##STR00047## in which: R3 denotes a hydrogen atom or a hydroxyl radical each of the substituents R1 independently denotes a hydrogen atom or a linear C1-C6 alkyl or a branched C3-C6 alkyl ##STR00048## in which: when R2 denotes a hydroxyl radical, then R3 denotes a hydrogen atom, when R2 denotes a hydrogen atom, then R3 denotes a hydroxyl radical, each of the substituents R1 independently denotes a hydrogen atom or a linear C1-C6 alkyl or a branched C3-C6 alkyl ##STR00049## in which R1 independently denotes a hydrogen or a linear C1-C6 alkyl or a branched C3-C6 alkyl.

13. A cosmetic composition comprising, in a physiologically acceptable medium, at least one compound of formula (I) ##STR00050## in which n=0; 1; 2 or 3 m=0; 1; 2 or 3 with 1≦m+n≦3 R1 independently denotes a linear C1-C6 alkyl radical or a branched C3-C6 alkyl radical or a linear C1-C6 acyl radical, R2 and R3 independently denote a hydrogen atom or an OH radical, an optical isomer, stereoisomer and/or diastereoisomer thereof and/or salts thereof, provided that when R1 denotes methyl, R2 denotes a OH radical, and R3 denotes a hydrogen atom then 2≦m+n≦3, with the exception of the following compound; ##STR00051##

14. The composition as claimed in claim 13, in which the compound of formula (I) is present, alone or as a mixture, in an amount of between 0.01% and 30% by weight relative to the total weight of the composition.

15. The composition as claimed in claim 13, comprising at least one cosmetic ingredient chosen from water; organic solvents; hydrocarbon-based oils, silicone oils, fluoro oils, waxes, pigments, fillers, dyes, surfactants, emulsifiers, cosmetic or dermatological active agents, UV-screening agents, film-forming polymers, hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic thickeners, preserving agents, fragrances, odor absorbers and antioxidants.

16. The composition as claimed in claim 13, in which the physiologically acceptable medium comprises at least one cosmetic active agent other than the compounds of formula (I) chosen from: desquamating agents; moisturizers; depigmenting or propigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents for stimulating the synthesis of dermal or epidermal macromolecules and/or for preventing their degradation; agents for stimulating fibroblast and/or keratinocyte proliferation or for stimulating keratinocyte differentiation; dermo-decontracting agents; tensioning agents; agents acting on microcirculation; agents acting on the energy metabolism of cells; and mixtures thereof.

17. A composition comprising, in a physiologically acceptable medium, at least one novel compound of formulae (V) to (IX) as defined in claim 12.

18. A non-therapeutic cosmetic process for treating the skin, comprising the application to the skin of a cosmetic composition as defined in claim 13.

19. The process as claimed in claim 18, in which the composition is applied to mature and/or wrinkled skin.

20. The process as claimed in claim 1, wherein the signs on the skin are chosen from wrinkled skin, skin exhibiting impairment of its viscoelastic or biomechanical properties, skin exhibiting impairment in the cohesion of its tissues, thinned skin, and skin exhibiting impairment of its surface appearance.

Description

EXAMPLE 1—SYNTHESIS OF COMPOUND 1

[0145] ##STR00027##

[0146] 1st Step

[0147] A solution of m-CPBA (22.3 g, 129.3 mmol, 2 eq.) in dichloromethane is added dropwise to eugenol (10.6 g, 64.6 mmol, 1 eq.) predissolved in dichloromethane (100 mL). The reaction mixture is stirred at room temperature for 12 hours and then worked up with aqueous Na.sub.2SO.sub.3 solution (conc. 10%, 200 mL) to neutralize the oxidizing agent. The phases are separated and the organic phase is washed twice with aqueous 10% NaHCO.sub.3 solution, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 25/1) to give the epoxide intermediate (6.4 g, 55% yield).

[0148] 2nd Step

[0149] A solution of the intermediate epoxide (6.4 g, 35.5 mmol), obtained from the first step, in methanol (80 mL) is stirred in the presence of 10% Pd/C catalyst (1.0 g) under an atmosphere of dihydrogen for 24 hours. The catalyst is removed by filtration and the filtrate is then concentrated to dryness. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 5/1) to give compound 1 in the form of a white powder (2.9 g, 45% yield).

[0150] The .sup.1H NMR spectra and mass spectra are in accordance with the expected structure.

EXAMPLE 2—SYNTHESIS OF COMPOUND 2

[0151] ##STR00028##

[0152] Propylene oxide (8.3 g, 142.8 mmol) is added dropwise to a solution of 1,3,4-trimethoxybenzene (6.0 g, 35.7 mmol) in THF (100 mL) at 40° C. The reaction mixture is maintained at this temperature for 2 hours and then cooled to room temperature. A solution of n-BuLi in hexane (1.6 M, 17.1 mL, 14.4 mmol) is added dropwise and the reaction mixture is then stirred at room temperature for 1 hour. The excess base is neutralized by adding saturated aqueous NH.sub.4Cl solution (20 mL) and the mixture is extracted 3 times with 50 mL of ethyl acetate. The organic phases are combined, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 10/1) to isolate compound 2 in the form of a pale yellow oil (4.2 g, 52% yield).

[0153] The .sup.1H NMR spectra and mass spectra are in accordance with the expected structure.

EXAMPLE 3—SYNTHESIS OF COMPOUND 3

[0154] ##STR00029##

[0155] Propylene oxide (2.8 g, 48 mmol) is added dropwise to a solution of 1,2,5-trimethoxybenzene in THF (100 mL) at 40° C. The reaction mixture is maintained at this temperature for 2 hours and then cooled to room temperature. A solution of n-BuLi in hexane (1.6 M, 9 mL, 14.4 mmol) is added dropwise and the reaction mixture is then stirred at room temperature for 1 hour. The excess base is neutralized by adding saturated aqueous NH.sub.4Cl solution (20 mL) and the mixture is extracted 3 times with 50 mL of ethyl acetate. The organic phases are combined, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 10/1) to isolate compound 3 in the form of a white powder (500 mg, 18% yield).

[0156] The .sup.1H NMR spectra and mass spectra are in accordance with the expected structure.

EXAMPLE 4—SYNTHESIS OF COMPOUND 4

[0157] ##STR00030##

[0158] 1st Step

[0159] The sodium ethoxide solution is prepared by adding sodium (4.0 g, 174 mmol) portionwise to absolute ethanol (500 mL) at 0° C. After total consumption of the sodium, 2,6-dimethoxyphenol (19.8 g, 129 mmol) is added dropwise at 0° C. under an inert atmosphere. After addition, the reaction medium is stirred at room temperature for 2 hours. 3-Bromopropene (20 g, 165 mmol) is then added dropwise and the medium is stirred for 16 hours. After concentrating under reduced pressure, the residue is dissolved in water and extracted with dichloromethane. The organic phases are combined, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 5/1) to give intermediate A in the form of a brown oil (20.0 g, 81% yield).

[0160] 2nd Step

[0161] Intermediate A is heated with stirring at 230° C. for 2 hours. The crude product thus obtained is purified by column chromatography on silica gel (hexane/EtOAc: 5/1) to give intermediate B in the form of a colorless oil (16.0 g, 80% yield).

[0162] 3rd Step

[0163] A mixture consisting of intermediate B (1.94 g, 10 mmol, 1 eq.), benzyl bromide (2.05 g, 12 mmol, 1.2 eq.) and potassium carbonate (2.07 g, 15 mmol, 1.5 eq.) in N,N-dimethylformamide (30 mL) is stirred at room temperature for 16 hours. The reaction medium is diluted by adding ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic phase is dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 5/1) to give intermediate C in the form of a yellowish oil (2.0 g, 70% yield).

[0164] 4th Step

[0165] Intermediate C (1.0 g, 3.5 mmol, 1 eq.) and the oxidizing system AD-mix-α (5 g, 3.5 mmol) in 50 mL of a water/t-BuOH mixture (1/1) are stirred at room temperature for 16 hours. The reaction medium is then diluted in water and extracted with ethyl acetate. The organic phases are combined, washed with aqueous Na.sub.2SO.sub.3 solution and then with saturated aqueous NaCl solution, dried over Na.sub.2SO.sub.4 and concentrated under vacuum. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 1/1) to give intermediate D in the form of a white solid (1.0 g, 90% yield).

[0166] 5th Step

[0167] Intermediate D (1.0 g, 3.3 mmol, 1 eq.) in dichloromethane (25 mL) is treated at 0° C. with tosyl chloride (760 mg, 4.0 mmol, 1.2 eq.) in the presence of triethylamine (710 mg, 7.0 mmol, 2.1 eq.). The reaction medium is stirred at 0° C. for 3 hours and then at room temperature for 16 hours. The mixture is then washed with aqueous H.sub.2SO.sub.4 solution (5%), then with aqueous NaHCO.sub.3 solution (5%) and then with saturated aqueous NaCl solution. The organic phase is then dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 3/1) to give intermediate E in the form of a white solid (900 mg, 60% yield).

[0168] 6th Step

[0169] Intermediate E (900 mg, 1.9 mmol, 1 eq.) predissolved in THF (5 mL) is added dropwise to a suspension of LiAlH.sub.4 (100 mg, 2.6 mmol) in THF (5 mL) at 0° C. The reaction medium is then stirred at room temperature for 5 hours. The mixture is poured onto a mixture of ice-water (10 mL) and aqueous 5N HCl solution (5 mL) and then extracted 3 times with ethyl acetate. The organic phases are combined, washed with saturated aqueous NaCl solution, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: gradient 3/1 to 1/1) to give intermediate F in the form of a white solid (500 mg, 60% yield).

[0170] 7th Step

[0171] Intermediate F (500 mg, 6.3 mmol) dissolved in ethanol (10 mL) is placed in contact with 10% Pd/C catalyst (10 mg). The reaction mixture is stirred under dihydrogen (0.1 MPa) at room temperature for 16 hours. The catalyst is removed by filtration and the filtrate is then concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: gradient 2/1 to 1/1) to give compound 4 in the form of a white solid (200 mg, 57% yield).

[0172] The .sup.1H NMR spectra and mass spectra are in accordance with the expected structure.

EXAMPLE 5—SYNTHESIS OF COMPOUND 5

[0173] ##STR00031##

[0174] 1st Step

[0175] A solution of m-CPBA (22.3 g, 129.3 mmol, 2 eq.) in dichloromethane is added dropwise to eugenol (10.6 g, 64.6 mmol, 1 eq.) predissolved in dichloromethane (100 mL). The reaction mixture is stirred at room temperature for 12 hours and then worked up with aqueous Na.sub.2SO.sub.3 solution (conc. 10%, 200 mL) to neutralize the oxidizing agent. The phases are separated and the organic phase is washed twice with aqueous 10% NaHCO.sub.3 solution, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 25/1) to give the epoxide intermediate (6.4 g, 55% yield).

[0176] 2nd Step

[0177] A solution of the intermediate epoxide (6.4 g, 35.5 mmol), obtained from the first step, in dichloromethane (50 mL) is treated with 50 mL of water and then 25 mL of aqueous 5% H.sub.2SO.sub.4 solution. The reaction mixture is stirred at room temperature for 24 hours and the dichloromethane is then removed by evaporation. The aqueous solution obtained is extracted three times with ethyl acetate. The organic phases are combined, dried over Na.sub.2SO.sub.4 and then concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (CH.sub.2Cl.sub.2/MeOH=20/1) to give compound 5 in the form of a yellow/orange oil (4.6 g, 65% yield).

[0178] The .sup.1H NMR spectra and mass spectra are in accordance with the expected structure.

EXAMPLE 6—SYNTHESIS OF COMPOUND 6

[0179] ##STR00032##

[0180] 1st Step

[0181] The sodium ethoxide solution is prepared by adding sodium (4.0 g, 174 mmol) portionwise to absolute ethanol (500 mL) at 0° C. After total consumption of the sodium, 2,6-dimethoxyphenol (19.8 g, 129 mmol) is added dropwise at 0° C. under an inert atmosphere. After addition, the reaction medium is stirred at room temperature for 2 hours. 3-Bromopropene (20 g, 165 mmol) is then added dropwise and the medium is stirred for 16 hours. After concentrating under reduced pressure, the residue is dissolved in water and extracted with dichloromethane. The organic phases are combined, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 5/1) to give intermediate A in the form of a brown oil (20.0 g, 81% yield).

[0182] 2nd Step

[0183] Intermediate A is heated with stirring at 230° C. for 2 hours. The crude product thus obtained is purified by column chromatography on silica gel (hexane/EtOAc: 5/1) to give intermediate B in the form of a colorless oil (16.0 g, 80% yield).

[0184] 3rd Step

[0185] A mixture consisting of intermediate B (1.94 g, 10 mmol, 1 eq.), benzyl bromide (2.05 g, 12 mmol, 1.2 eq.) and potassium carbonate (2.07 g, 15 mmol, 1.5 eq.) in N,N-dimethylformamide (30 mL) is stirred at room temperature for 16 hours. The reaction medium is diluted by adding ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic phase is dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 5/1) to give intermediate C in the form of a yellowish oil (2.0 g, 70% yield).

[0186] 4th Step

[0187] Intermediate C (1.0 g, 3.5 mmol, 1 eq.) and the oxidizing system AD-mix-α (5 g, 3.5 mmol, 1 eq.) in 50 mL of a water/t-BuOH mixture (1/1) are stirred at room temperature for 16 hours. The reaction medium is then diluted in water and extracted with ethyl acetate. The organic phases are combined, washed with aqueous Na.sub.2SO.sub.3 solution and then with saturated aqueous NaCl solution, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (hexane/EtOAc: 1/1) to give intermediate D in the form of a white solid (1.0 g, 90% yield).

[0188] 5th Step

[0189] Intermediate D (2.0 g, 6.3 mmol) dissolved in ethanol (10 mL) is placed in contact with 10% Pd/C catalyst (10 mg). The reaction mixture is stirred under dihydrogen (0.1 MPa) at room temperature for 16 hours. The catalyst is removed by filtration and the filtrate is then concentrated. The residue is purified twice by column chromatography on silica gel (hexane/EtOAc: gradient 1/2). To obtain a higher purity, the product is then recrystallized from an EtOH/hexane mixture and compound 6 is isolated in the form of a white solid (1.3 g, 90% yield).

[0190] The .sup.1H NMR spectra and mass spectra are in accordance with the expected structure.

EXAMPLE 7—SYNTHESIS OF COMPOUND 7

[0191] ##STR00033##

[0192] 1st Step: Protection of Isoeugenol

[0193] A mixture containing isoeugenol (5 g, 30.5 mmol, 1 eq.), potassium carbonate (6.3 g, 45.7 mmol, 1.5 eq.) and benzyl bromide (4.5 mL, 36.6 mmol, 1.2 eq.) in acetonitrile (80 mL) is refluxed for 12 hours. After cooling to room temperature, the mixture is diluted by adding 100 mL of water and then extracted 3 times with dichloromethane. The organic phases are combined, washed with saturated aqueous NaCl solution and then dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (100% hexane) to give benzylated isoeugenol in the form of a white solid (7.4 g, 96% yield).

[0194] 2nd Step: Dihydroxylation of the Protected Isoeugenol

[0195] The benzylated isoeugenol intermediate is added to a solution at 0° C. of oxidizing agent AD-mix-β in a t-BuOH/water mixture (1/1, 400 mL). The reaction medium is stirred vigorously for 24 hours. The excess oxidizing agent is neutralized by adding Na.sub.2SO.sub.3 (36 g). After separation of the phases by settling, the organic phase is collected and the aqueous phase is extracted 3 times with ethyl acetate. The organic phases are combined, dried over Na.sub.2SO.sub.4 and concentrated. The residue is purified by column chromatography on silica gel (CH.sub.2Cl.sub.2/MeOH: 500/4) to give the protected diol intermediate in the form of a colorless oil (7.5 g, 96% yield).

[0196] 3rd Step: Deprotection of the Intermediate Diol

[0197] The protected diol intermediate obtained from the second step (6.46 g, 22.4 mmol) dissolved in methanol (100 mL) is placed in contact with 10% Pd/C catalyst (0.65 g). The reaction mixture is stirred under an atmosphere of dihydrogen at room temperature for 24 hours. The catalyst is removed by filtration and the filtrate is then concentrated under vacuum to give compound 7 in the form of a white powder (4.0 g, 90% yield).

[0198] The .sup.1H NMR spectra and mass spectra are in accordance with the expected structure.

EXAMPLE 8

[0199] Normal human epidermal keratinocytes are seeded at 180 000 cells per well and cultured in SFM culture medium (supplier Gibco) supplemented with 0.25 ng/ml EGF, 25 μg/ml of pituitary extract and 25 μg/ml gentamicin, up to confluence, and incubated in a humid oven at 37° C. and 5% CO2. The culture medium was then replaced with test medium (SFM (Gibco) supplemented with 25 μg/ml gentamicin) containing or not containing (control) the test compounds, or the references (AICAR—(5-amino-4-imidazole carboxamide riboside) at 500 μM). The cells were then incubated for 18 or 48 hours.
The level of expression of p-AMPK was analyzed by Western blotting.
At the end of the incubation, the proteins were extracted and quantified and then separated by electrophoresis on 10% polyacrylamide gel and then transferred onto a nitrocellulose membrane.
After saturation of the membranes in PBS/Tween/1% BSA solution, the phospho-AMPK proteins (Thr-172) (p-AMPK) and GAPDH were successively revealed using specific antibodies that were themselves revealed using an anti-immunoglobulin-peroxidase conjugate. After washing with PBS/Tween, the peroxidase activity and thus the proteins of interest was revealed via the ECL+ (enhanced chemiluminescence) method. Between each successive revelation, the antibodies were detached using a “stripping” buffer. The images were acquired with a Fuji LAS 3000 chemiluminescence scanner (Fujifilm) and the densitometric analyses were performed using the Multigauge software (Fujifilm).

[0200] An increase in the phosphorylated form of AMPK (active form of the enzyme) relative to the control is evaluated in this test.

[0201] Results

[0202] Expressed in the form of the p-AMPK/GAPDH ratio relative to the control (100%):

TABLE-US-00003 Incubation time Measured ratio compound 1 μM 10 μM 100 μM 500 μM 18 hours p- control 100% ± 27% AMPK/AMPK AICAR — — — 177% ± 31% 1 — — 132% ± 11% 48 hours p- control 100% ± 7%  AMPK/GAPDH AICAR — — — .sup. 279 ± 96% 5 .sup. 116 ± 17% 149 ± 25% 136 ± 14% —

EXAMPLE 9

[0203] The following anti-aging composition is prepared:

[0204] The percentages are indicated on a weight basis.

TABLE-US-00004 Compound 5 of Example 5  1% Glycerol 12% Polyacrylamide at 40% AM (Sepigel 305 1% AM from SEPPIC) Preserving agents qs Fragrance qs Water qs 100% 
AM: active material
When applied to the skin, this cream reduces the signs of aging of the skin.