NOVEL USE OF PROLINE DERIVATIVES

Abstract

The present invention relates to a novel use of proline containing dipeptides for evening out as well as brightening the skin tone. These proline containing dipeptides are furthermore particular suitable for improving the skin tone of the cheek under the eyes, on the cheek and the jawline.

Claims

1. Use of a compound of formula (I). ##STR00002## wherein n represents 0, 1 or 2, R.sup.1 and R.sup.4—independently of each other—are selected from the group consisting of H, C.sub.1-C.sub.6alkyl, amidino or tetra-C.sub.1-C.sub.6-alkylamidinium, R.sup.2 is H or C.sub.1-C.sub.6-alkyl, or R.sup.1 and R.sup.2 together with the residue to which they are bound form a 5- to 7-membered, saturated ring, R.sup.3 is selected from the group consisting of C.sub.1-C.sub.6alkyl, arC.sub.1-C.sub.6alkyl and heteroarylC.sub.1-C.sub.6alkyl, and R.sup.5 is H or, when n is 1, also NH.sub.2, or R.sup.5 and R.sup.1 together with the residue to which they are bound form a 5- to 7-membered, saturated ring, or a cosmetically acceptable salt thereof for evening out skin tone, for brightening of skin, for reducing inflammation-related discoloration, erythema and/or pigmentation of skin and/or for reducing dark circles under the eye area.

2. The use according to claim 1, wherein the L* value of the skin is increased and the a* value is decreased compared to non-treated skin.

3. The use according to claim 1, wherein R.sup.1, R.sup.4 and R.sup.5 are H.

4. The use according to claim 1, wherein R.sup.3 is arC.sub.1-C.sub.6alkyl, preferably benzyl.

5. The use according to claim 1, wherein n is 0 or 1, preferably 1.

6. The use according to claim 1, wherein R.sup.1, R.sup.2, R.sup.4 and R.sup.5 are H, R.sup.3 is benzyl and n is 1.

7. The use according to claim 1, wherein the compound of formula (I) is H-(beta-Ala)-Pro-Dab-NH-benzyl, in particular in the form of its diacetate.

8. A method to even out skin tone, to brighten skin, to reduce inflammation-related discoloration, erythema and/or pigmentation of skin and/or to reduce dark circles under the eye, said method comprises topically administering an effective amount of a cosmetic composition comprising at least one compound of formula (I) to the appropriate skin area of a person in need of such treatment.

9. A method according to claim 8 to even out skin tone and/or to brighten the skin, wherein the L* value of the skin is increased and the a* value is decreased compared to non-treated skin.

10. The method according to claim 8, wherein the amount of the at least one compound of formula (I) in the cosmetic composition is selected in the range of 0.5 ppm to 5,000 ppm, preferably in the range of 2.5 ppm to 250 ppm, most preferably in the range of 25 ppm to 100 ppm, based on the total weight of the composition.

11. The method according to claim 8, wherein the amount of the cosmetic composition to be applied to the skin is selected in the range of 0.1 to 3 mg/cm.sup.2 skin, preferably in the range of 0.1 to 2 mg/cm.sup.2 skin, most preferably in the range of 0.5 to 2 mg/cm.sup.2 skin.

12. The method according to claim 8, wherein the cosmetic composition is applied once or twice daily.

13. The method according to claim 8, wherein the cosmetic composition is a skin care preparation.

14. The method according to claim 8, wherein the composition is an O/W emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O/W emulsifier.

15. The method according to claim 14, wherein the O/W emulsifier is a cetyl phosphate.

Description

EXPERIMENTAL PART

1. Material & Methods

[0061] This was a placebo controlled, full face, and parallel groups study. Volunteers had to apply the cosmetic formulations twice daily for 29 days. 54 female Asian volunteers participated in the study divided into Placebo group and Active group (formulation containing 4% SYN®-AKE).

[0062] The volunteers were photographed with cross polarized lighting of a Visia CR® device (Canfield, Parsippany, US) at 45° angles from left and right. L*a*b* values were calculated directly on images using a defined algorithm. Differences were computed and significances calculated using Studen's t-test (if values followed a normal distribution) or Wilcoxon Signed Rank test (if value did not follow a normal distribution).

2. Clinical Study

[0063] A double blind parallel group study was performed with Asian female volunteers aged 41-55. 27 volunteers (mean age 47 years) received a placebo formulation and 27 volunteers (mean age 48 years) received the active formulation containing SYN®-AKE. The placebo respectively active formulation was applied twice daily for 28 days to face. At the end of the study pictures were taken for computational analysis of skin tone as outlined above.

TABLE-US-00001 TABLE 1 Placebo/Active formulation Placebo Active Ingredients INCI Name [%] AMPHISOL ® K POTASSIUM CETYL 1.00 1.00 PHOSPHATE Ecorol 16/98P CETYL ALCOHOL 3.00 3.00 Cutina CP CETYL PALMITATE 1.50 1.50 Eutanol G OCTYLDODECANOL 3.00 3.00 Pemulen TR-1 ACRYLATES/C10-30 ALKYL 0.10 0.10 ACRYLATE CROSSPOLYMER 1,3-Butylenglycol BUTYLENE GLYCOL 3.00 3.00 WATER DEM. AQUA Ad 100 Ad 100 Dow Corning 345 CYCLOPENTASILOXANE, 2.50 2.50 Fluid CYCLOHEXASILOXANE Natriumhydroxid AQUA, SODIUM HYDROXIDE 0.09 0.09 30% SYN ®-AKE Dipeptide Diaminobutyroyl 0 4.00 Benzylamide Diacetate, Glycerin, Aqua Euxyl PE 9010 PHENOXYETHANOL, 1.00 1.00 ETHYLHEXYLGLYCERIN Frag 49424902 Perfume 0.05 0.05 Chloe

3. Results

[0064]

TABLE-US-00002 L* value a* value difference: difference: day 29 Significance day 29 to Significance Facial area to day 0 (p-value) day 0 (p-value) Forehead Placebo −0.05 0.705 −0.06 0.443 Invention 0.36 0.064 −0.24 0.040 Cheek under eyes (dark circles) Placebo −0.13 0.744 −0.09 0.082 Active 0.36 0.016 −0.35 0.018 Cheek Placebo 0.10 0.185 −0.12 0.071 Active 0.29 0.081 −0.26 0.057 Jawline Placebo 0.07 0.502 −0.13 0.360 Active 0.09 0.671 −0.29 0.026

[0065] As can be retrieved from the results a significant improvement in the skin tone was observed versus the Placebo formulation not containing the active.