Carboxylated polyphenol derivatives and their cosmetic use

Abstract

A subject matter of the present invention is the cosmetic use of at least one compound of formula (I): in which: (II) denotes a divalent radical chosen from a carbon-carbon single bond *—CH.sub.2—CH.sub.2—* or double bond *—CH═CH—*, of Z or E configuration or their mixtures, b=0 or 1, c=0 or 1, d=0, 1 or 2, and R and R′ independently denote a hydrogen atom, a linear C.sub.1-C.sub.6 alkyl radical or a branched C.sub.3-C.sub.6 alkyl radical, to treat and/or prevent signs of aging and/or of photoaging of keratinous substances, preferably of the skin, and/or to depigment, lighten and/or whiten keratinous substances, preferably the skin. The present invention also relates to novel compounds and to a corresponding cosmetic method. ##STR00001##

Claims

1. A method for the cosmetic treatment of keratinous substances, comprising applying to the keratinous substances, a composition, comprising at least one compound of formula (III): ##STR00031## wherein: c=0 or 1, wherein, if c=1, then the COOR′ group is in the ortho position with respect to a phenol functional group, and R and R′ independently denote a hydrogen atom, a linear C.sub.1-C.sub.6 alkyl radical or a branched C.sub.3-C.sub.6 alkyl radical, one of its stereoisomers and/or solvates and/or one of its salts.

2. A method for the cosmetic treatment of keratinous substances, comprising applying to the keratinous substances, a composition, comprising at least one compound of formula (III′): ##STR00032## wherein: c=0 or 1, wherein, if c=1, then the corresponding carboxylate functional group is in the ortho position with respect to a phenol functional group, and R and R′ independently denote a hydrogen atom, a linear C.sub.1-C.sub.6 alkyl radical or a branched C.sub.3-C.sub.6 alkyl radical one of its stereoisomers and/or solvates and/or one of its salts.

3. A method for the cosmetic treatment of keratinous substances, comprising applying to the keratinous substances, a composition, comprising, at least one compound of formula (IV): ##STR00033## wherein: c=0 or 1, d=0, 1 or 2, wherein, if c=1, then d≥1 and the COOR′ group is in the ortho position with respect to a phenol functional group, and R and R′ independently denote a hydrogen atom, a linear C.sub.1-C.sub.6 alkyl radical or a branched C.sub.1-C.sub.6 alkyl radical, one of its stereoisomers and/or solvates and/or one of its salts.

4. A method for the cosmetic treatment of keratinous substances, comprising applying to the keratinous substances, a composition, comprising at least one compound of formula (V): ##STR00034## wherein: R denotes a linear C.sub.1-C.sub.6 alkyl radical or a branched C.sub.3-C.sub.6 alkyl radical, one of its stereoisomers and/or solvates and/or one of its salts.

5. A method for the cosmetic treatment of keratinous substances comprising: applying to keratinous substances a composition comprising at least one compound of formula (W): ##STR00035## wherein the compound of formula (W) is used to depigment, lighten and/or whiten keratinous substances.

Description

EXAMPLES

Example 1

Preparation of Compound X

(1) ##STR00028##

(2) The substrate (A-X), in solution in methanol (50 mg in 1 ml), is added to 19 ml of a phosphate buffer solution at pH 5.5 containing the whole cells (651 mg, producing the decarboxylase specific for 2,6-dihydroxybenzoic acid isolated from Rhozobium sp.). This mixture is subsequently added to a 3M aqueous potassium hydrogencarbonate KHCO.sub.3 solution. The flask containing the reaction medium is sealed and stirred at 30° C. for 24 hours.

(3) The reaction is interrupted by addition of a 6M aqueous HCl solution, until a pH of 2 is obtained. The aqueous phase thus obtained is extracted 4 times with ethyl acetate (10 ml). The organic phases are combined and dried over sodium sulfate. The solvent is evaporated under reduced pressure and the residue is purified by silica gel column chromatography (dichloromethane/methanol: 90/10), to result in the product (X) in the form of an offwhite/yellow solid (yield: 45%).

(4) The .sup.1H NMR spectrum and the mass spectrum are in accordance with the expected structure.

Example 2

Preparation of the Compounds Y and Y′

(5) ##STR00029##

(6) Oxyresveratrol (A-Y), in solution in methanol (50 mg in 1 ml), is added to 19 ml of a phosphate buffer solution at pH 5.5 containing the whole cells (651 mg, producing the decarboxylase specific for 2,6-dihydroxybenzoic acid isolated from Rhozobium sp.). This mixture is subsequently added to a 3M aqueous potassium hydrogencarbonate KHCO.sub.3 solution. The flask containing the reaction medium is sealed and stirred at 30° C. for 24 hours.

(7) The reaction is interrupted by addition of a 6M aqueous HCl solution, until a pH of 2 is obtained. The aqueous phase thus obtained is extracted 4 times with ethyl acetate (10 ml). The organic phases are combined and dried over sodium sulfate. The solvent is evaporated under reduced pressure. The crude reaction product thus obtained corresponds to the mixture of (Y), (Y′) and (Y″):

(8) ##STR00030##

(9) The residue is purified by silica gel column chromatography (dichloromethane/methanol: 90/10), to isolate the product (Y) in the form of an offwhite/yellow solid (yield: 66%).

(10) The .sup.1H NMR spectrum and the mass spectrum are in accordance with the expected structure.

Example 3

Demonstration of the Depigmenting Activity

(11) The effectiveness was demonstrated on the basis of the following test:

(12) The evaluations of the effect of prevention of or of decrease in the pigmentation of the skin and/or of lightening of the latter can be carried out in the following way.

(13) The measurement of the depigmenting activity (reduction in the production of melanin) of compounds of formula (I) was performed by assaying the melanin produced by normal human melanocytes in vitro as follows.

(14) First of all, normal human melanocytes are cultured and dispensed into 384 wells. After 24 hours, the culture medium was replaced with a medium containing compounds of formula (I) to be evaluated. The cells were incubated for 72 hours before measurement of the final optical density, which measures the amount of melanin produced by the melanocytes. A dose effect is performed using a wide concentration range of the compounds evaluated. Thus, by making the concentrations and the measurements of melanin correspond, it is possible to determine an IC50 in μM: concentration at which 50% decrease in melanin synthesis is achieved.

(15) The compound W was in particular tested and showed a depigmenting effect.

(16) Thus, the compound W shows an inhibiting effect on the production of melanin with an IC50 value of 25 μM, without cytotoxicity in the concentration range tested. The measurements at the different concentrations are collated in table II below.

(17) TABLE-US-00002 TABLE II Mean percentage Percentage Standard Concentration Depigmentation deviation 0.0002 125.6 4.6 0.0001 99.7 1.1 0.00005 76.7 2.9 0.000025 43.0 3.7 0.0000125 32.8 6.2 0.00000625 22.8 4.1 0.000003125 15.6 2.0 1.5625*10.sup.−6 9.7 1.7 7.8125*10.sup.−7 5.5 4.3 3.90625*10.sup.−7  −0.9 2.9

Example 4

Demonstration of the Anti-Aging Activity

(18) The effectiveness was demonstrated on the basis of the following tests:

(19) The evaluations of the effect of activation of hyaluronic acid (HA) biosynthesis can be carried out in the following ways.

(20) Gene Markers Expression

(21) Human epidermal keratinocytes were seeded in 48 well-culture plate and cultured for 48 hours at 37° C. and 5% of CO.sub.2 in culture medium with renewal of culture medium after the first 24 hours. At the end of incubation, culture medium was replaced by assay medium containing or not (control) raw material and cells were incubated for additional 24 hours. All experimental conditions were performed in n=3. At the end of treatment, cells were washed twice in PBS (w/o CaCl.sub.2, w/o MgCl.sub.2) and RNA extraction was performed using MagMAX™-96 Total RNA Isolation Kit (Ambion cat no AM8130) according to manufacturer recommendation. RNA quantification and quality control were performed using Labchip GX (Perkin Elmer). Relative expression of selected markers was measured by two steps RT-qPCR. In a first step, a reverse transcription was performed using the Quantitect® Reverse transcription kit (QIAGEN) and according to manufacturer recommendation. Then, PCR experiments were performed using a LightCycler® 480 Real-Time PCR System measuring SYBR® Green incorporation (Roche).

(22) The compound W was in particular tested and showed an effect on HAS3 expression. Indeed, the compound W is able to increase the expression of the HAS3 marker without cytotoxicity at 30 μM, with a fold change of 2.45 vs control. The measurements are collated in table III and figure I below.

(23) TABLE-US-00003 TABLE III Relative expression Fold change P Treatment Concentration (UA) (Nb) Mean sd (vs control) Control — 1.34E−03 0.9449488 1.00 0.06 — 1.40E−03 0.99192853 1.50E−03 1.06312267 Compound W 30 μM 3.61E−03 2.55336543 2.45 0.10 4.11E−03 3.44E−03 2.43243293 3.32E−03 2.34957534

(24) Thus, compound W is able to stimulate the expression of the HAS3 marker by keratinocytes, which is the gene coding for hyaluronic acid synthase. Hence, since hyaluronic acid is an important constituent of extracellular matrix, playing major role for instance in mechanical properties of dermis, compound W has thus been proven as improving skin firmness, and more largely as showing anti-aging effect.

Example 5

Example of Composition in Accordance With the Invention

(25) The percentages of compounds shown are percentages by weight, with respect to the total weight of the composition in which they are present.

(26) TABLE-US-00004 Compound W  1% Carbomer (Carbopol 981 from Lubrizol) 1% AM Preservatives q.s. Water q.s. for 100% AM: Active material

(27) The above composition, applied topically to the skin, makes it possible to attenuate brown blemishes.