Use of gingerone or derivatives thereof for reducing or delaying the signs of skin ageing

Abstract

The present invention relates to the cosmetic use of at least one compound of general formula (I): ##STR00001##
in which: R.sub.1 represents a methyl or ethyl radical; R.sub.2 represents a hydrogen atom or a methyl or ethyl radical; R.sub.3 represents a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical, or a linear C.sub.2-C.sub.6 or branched C.sub.3-C.sub.6 alkenyl radical; and X represents ═O or —OH,
as an agent for reducing and/or delaying the signs of skin ageing.

Claims

1. A method for treating appearance of wrinkles, appearance of fine lines, thinning of the skin, dryness of the skin, or any combination thereof of skin on a subject having skin including appearance of wrinkles, appearance of fine lines, thinning of the skin, dryness of the skin, or any combination thereof, comprising: applying to the appearance of wrinkles, appearance of fine lines, thinning of the skin, dryness of the skin, or any combination thereof, a compound of general formula (I) in an amount sufficient to treat the appearance of wrinkles, appearance of fine lines, thinning of the skin, dryness of the skin, or any combination thereof and in an amount sufficient to stimulate filaggrin protein expression in a human epidermal keratinocyte: ##STR00012## wherein: R.sub.1 is an ethyl radical; R.sub.2 is a hydrogen atom, a methyl radical or an ethyl radical; R.sub.3 is a linear C.sub.1-C.sub.6 alkyl radical, a branched C.sub.3-6 alkyl radical, a linear C.sub.2-C.sub.6 alkenyl radical, or a branched C.sub.3-C.sub.6 alkenyl radical; and X is ═O or —OH.

2. The method according to claim 1, wherein R.sub.3 is a C.sub.1-C.sub.6 linear alkyl.

3. The method according to claim 1, wherein the compound of general formula (I), alone or as a mixture, is at least one selected from the group consisting of: ##STR00013##

4. The method according to claim 1, wherein the compound of general formula (I) is ethyl gingerone.

5. The method according to claim 1, wherein the method comprises applying to the appearance of wrinkles a compound of general formula (I) in an amount sufficient to treat the appearance of wrinkles.

6. The method according to claim 1, wherein the compound of general formula (I) is present m a composition comprising a physiologically acceptable medium, wherein the compound of general formula (I) is present in the composition in a content between 0.1% and 10% by weight relative to a total weight of the composition.

7. The method according to claim 1, wherein the compound is applied in a cosmetic composition comprising the compound of general formula (I) in an amount of 0.1% to 10% by weight relative to a total weight of the cosmetic composition.

8. The method according to claim 7, wherein the cosmetic composition is a lotion.

9. The method according to claim 7, wherein the cosmetic composition is a gel.

10. A method for treating appearance of wrinkles, appearance of fine lines, or any combination thereof of skin on a subject having skin including appearance of wrinkles, appearance of fine lines; or any combination thereof comprising: applying to the appearance of wrinkles, appearance of fine lines, or any combination thereof, a compound of general formula (I) in an amount sufficient to treat the appearance of wrinkles, appearance of fine lines, or any combination thereof and in an amount sufficient to stimulate filaggrin protein expression in a human epidermal keratinocyte: ##STR00014## wherein: R.sub.1 is an ethyl radical; R.sub.2 is a hydrogen atom or a methyl or ethyl radical: R.sub.2 is a hydrogen atom, a methyl radical or an ethyl radical; R.sub.3 is a linear C.sub.1-C.sub.6 alkyl radical, a branched C.sub.3-C.sub.6 alkyl radical, a linear C.sub.2-C.sub.6 alkenyl radical, or a branched C.sub.3-C.sub.6 alkenyl radical; and X is ═O or —OH.

11. The method according to claim 10, wherein R.sub.3 is a C.sub.1-C.sub.6 linear alkyl.

12. The method according to claim 10, wherein the compound of general formula (I), alone or as a mixture, is at least one selected from the group consisting of: ##STR00015##

13. The method according to claim 10, wherein the compound of general formula (I) is ethyl gingerone.

14. The method according to claim 1, comprising treating signs of chronobiological ageing in a subject suffering from internal degradations of the skin due to intrinsic ageing of the individual.

15. The method according to claim 1, wherein the method comprises applying to the appearance of fine lines a compound of general formula (I) in an amount sufficient to treat the appearance of fine lines.

16. The method according to claim 1, wherein the method comprises applying to the thinning of the skin a compound of general formula (I) in an amount sufficient to treat the thinning of the skin.

17. The method according to claim 1, wherein the method comprises applying to the dryness of the skin a compound of general formula (I) in an amount sufficient to treat the dryness of the skin.

18. The method according to claim 6, wherein the composition does not contain anti-UV screening agents.

Description

EXAMPLES

1. Method of Preparing a Compound According to the Invention

(1) The method of preparing these compounds of general formula (I) may be, for example, the following:

(2) ##STR00010##

(3) The method of preparing compound 3 comprises a supplementary reduction step:

(4) ##STR00011##

(5) The compounds according to the invention are prepared here either from commercial vanillin (CAS: 121-33-5), or from commercial ethyl vanillin (CAS: 121-32-4).

2. Demonstration of the Activity of a Compound According to the Invention

(6) The in vitro effect of gingerone (compound 1, the chemical formula of which is given above) on keratinocyte differentiation is studied. The expression and the location of the marker of filaggrin differentiation are especially studied in keratinocytes in culture which thus makes it possible to evaluate the capacity of this compound to increase the differentiation of these cells.

(7) Procedure:

(8) Normal human keratinocytes (NHEKs) were cultured at 37° C. and 5% CO.sub.2 for 24 h in a complete SFM medium until moderate confluence was obtained. A complete SFM medium is an SFM culture medium supplemented with pituitary extract (25 μg/ml), EGF (0.25 ng/ml) and gentamicin (25 μg/ml).

(9) At the end of the incubation, the medium was withdrawn and replaced with culture medium that did or did not contain various concentrations of the test product or reference molecules. Calcium chloride and retinoic acid, which are known respectively as a stimulator and as an inhibitor of the keratinocyte differentiation, were used as reference molecules for this test. The keratinocytes were then incubated for 144 hours. The treatments were carried out in triplicate (n=3).

(10) At the end of the incubation, the culture medium was removed and the cells were rinced, fixed, permeabilized then labelled with the primary antibody targeted against the filaggrin protein of interest (in situ immunolabelling). This antibody was then revealed by a secondary antibody coupled to a fluorochrome (GAM-Alexa 488). At the same time, the nuclei of the cells were stained with Hoechst 33258 (bisbenzimide).

(11) Image acquisition was carried out using an INCell Analyzer™1000 machine. The labels were quantified by measuring the fluorescence intensity of the proteins relative to the number of nuclei identified by the Hoechst product.

(12) Results

(13) The results are given in Table 1 below:

(14) TABLE-US-00002 TABLE 1 % relative to Treatment the control Control complete SFM 100  medium CaCl.sub.2 1.5 mM  158** Retinoic acid 10.sup.−7 M   3** Gingerone 2 μg/ml 133* 20 μg/ml 151* Significant difference relative to the control medium (*p < 0.05 and **p < 0.01). Under the experimental conditions of this study, the treatment with calcium chloride, pro-differentiating reference molecule, substantially increases the expression of filaggrin by the keratinocytes (+58% relative to the control). Under the experimental conditions of this study, the treatment with retinoic acid, anti-differentiating reference molecule, substantially decreases the expression of filaggrin by the keratinocytes (−97% relative to the control). The treatment with gingerone at 2 μg/ml and 20 μg/ml significantly and dose-dependently stimulates the expression of filaggrin (+33% and +51% respectively relative to the control) by the keratinocytes.
Conclusion

(15) Gingerone significantly and dose-dependently increases the expression of the filaggrin protein in normal human epidermal keratinocytes.

(16) The results obtained thus translate into an increase in epidermal differentiation. Gingerone therefore has a pro-differentiating effect on normal human keratinocytes and therefore can thus reduce and/or delay the signs of skin ageing.

3. Composition Examples

(17) 3.1. Lotion

(18) A lotion is prepared, comprising (% by weight):

(19) TABLE-US-00003 compound tested in Example 1 (gingerone) 0.75% glycerol   2% ethyl alcohol   20% demineralized water qs 100%

(20) The composition according to the invention applied daily to the face makes it possible to combat the signs of skin ageing.

(21) 3.2. Facial Gel

(22) A facial gel is prepared, comprising (% by weight):

(23) TABLE-US-00004 glyceryl polyacrylate (Norgel) 30%  polyacrylamide/C13-14 isoparaffin/laureth-7 (Sepigel 305) 2% silicone oil 10%  compound 1 (gingerone) 5% water qs 100% The composition according to the invention applied daily to the face makes it possible to combat the signs of skin ageing.