PEPTIDES, COMPOSITIONS COMPRISING THEM AND USES IN PARTICULAR COSMETIC USES

Abstract

The peptides have the general following formula: X-Pro*-Pro*-Xaa-Y in which: Xaa is selected from Leucine (Leu, L), Arginine (Arg, R), Lysine (Lys, K), Alanine (Ala, A), Serine (Ser, S), and Aspartic acid (Asp, D); At the N terminal end of the peptide, X is selected from H, COR1 and SO.sub.2R.sub.1; At the C terminal end of the peptide, Y is selected from OH, OR.sub.1, NH.sub.2, NHR.sub.1 and NR.sub.1R.sub.2; R.sub.1 and R.sub.2 are, independently from each other, selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulfured, and which skeletum can comprise an heteroatom, in particular an O, S and/or N atom; Pro* correspond to a Proline, an analogue or derivative thereof; if X is H then Y is selected from OR.sub.1, NH.sub.2, NHR.sub.1 and NR.sub.1R.sub.2, and if Y is OH then X is CO or SO.sub.2R.sub.1; and the peptide hypoxanthine-Pro-Pro-Arg being excluded. The invention provides the use of the peptides of above formula I to stimulate the synthesis of the molecules constituting the dermal extracellular matrix, including collagen I and IV and elastin. A cosmetic treatment according to the invention includes anti-aging, anti-wrinkles, improving mechanical properties of the skin, firmness/tone/elasticity/suppleness/flexibility, increasing density and volume of the skin, restructuring effect, fighting stretch marks, improving skin barrier and/or skin hydration.

Claims

1. Peptides of the general following formula:
X-Pro*-Pro*-Xaa-Y(I) wherein: Xaa is selected from Leucine (Leu, L), Arginine (Arg, R), Lysine (Lys, K), Alanine (Ala, A), Serine (Ser, S), and Aspartic acid (Asp, D); at the N terminal end of the peptide, X is selected from H, COR.sub.1 and SO.sub.2R.sub.1; at the C terminal end of the peptide, Y is selected from OH, OR.sub.1, NH.sub.2, NHR.sub.1 and NR.sub.1R.sub.2; R.sub.1 and R.sub.2, independently from each other, are selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulfured, and which backbone can comprise an heteroatom; Pro* is a Proline, an analogue or derivative thereof; if X is H then Y is selected from OR.sub.1, NH.sub.2, NHR.sub.1 and NR.sub.1R.sub.2, and if Y is OH then X is COR.sub.1 or SO.sub.2R.sub.1; and the peptide hypoxanthine-Pro-Pro-Arg being excluded of formula (I).

2. A topical composition comprising: at least one peptide of the general following formula:
X-Pro*-Pro*-Xaa-Y(I) Xaa is selected from Leucine (Leu, L), Arginine (Arg, R), Lysine (Lys, K), Alanine (Ala, A), Serine (Ser, S), and Aspartic acid (Asp, D); at the N terminal end of the peptide, X is selected from H, COR.sub.1 and SO.sub.2R.sub.1; at the C terminal end of the peptide, Y is selected from OH, OR.sub.1, NH.sub.2, NHR.sub.1 and NR.sub.1R.sub.2; R.sub.1 and R.sub.2, independently from each other, are selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulfured, and which backbone can comprise an heteroatom; Pro* is a Proline, an analogue or derivative thereof; and if X is H then Y is selected from OR.sub.1, NH.sub.2, NHR.sub.1 and NR.sub.1R.sub.2, and if Y is OH then X is COR.sub.1 or SO.sub.2R.sub.1; and a physiologically acceptable medium for a non-therapeutic cosmetic treatment or for a therapeutic treatment.

3. Peptide according to claim 1, wherein in formula I, Pro* is Proline.

4. Peptide according to claim 1, wherein Xaa is selected from Leucine (Leu, L) and Arginine (Arg, R), the peptide being X-PPL-Y or X-PPR-Y.

5. Peptide according to claim 1, wherein R.sub.1 and/or R.sub.2 is an alkyl chain of 1 to 24 carbon atoms.

6. Peptide according to claim 1, wherein R.sub.1 and/or R.sub.2 is an alkyl chain of 3 to 24 carbon atoms.

7. Peptide according to claim 1, wherein X is an acyl group COR.sub.1 and Y is selected from OH, OMe, OEt and NH.sub.2.

8. Peptide according to claim 7, wherein Y is OH.

9. Peptide according to claim 1, wherein X is an acyl group COR.sub.1 selected from octanoyle (C.sub.8), decanoyle (C.sub.10), lauroyl (C.sub.12), myristoyle (C.sub.14), palmitoyle (C.sub.16), stearoyle (C.sub.18), biotinoyle, elaidoyle, oleoyle and lipoyle.

10. Peptide according to claim 9, wherein X is selected from myristoyle (C.sub.14) and palmitoyle (C.sub.16).

11. Peptide according to claim 10, wherein X is a myristoyle.

12. Peptide according to claim 11, wherein the peptide is selected from Myr-PPL-OH and Myr-PPR-OH.

13. (canceled)

14. A method for a therapeutical treatment of a skin deficient in molecules constituting the dermal extracellular matrix, comprising applying to the skin of a person in need thereof a peptide according to claim 1 to stimulate synthesis of at least one molecular constituting the dermal extracellular matrix.

15. A method for a topical cosmetic treatment, comprising applying a peptide according to claim 1 to skin.

16. (canceled)

17. for the method according to claim 15, wherein the topical cosmetic treatment is an anti-ageing treatment.

18. The method according to claim 15, wherein the topical cosmetic treatment is a treatment: Of wrinkles and fine lines, and/or For ameliorating the mechanical properties of skin, firming, toning, elasticity, flexibility and suppleness, and/or For increasing the density and volume of skin (volumating or re-pulping effect), and/or For restructuring skin, For fighting stretchmarks, For improving skin barrier, and/or For skin hydration.

19. Peptide according to claim 1, wherein the backbone of R.sub.1 and/or R.sub.2 comprises a heteroatom selected from O, S, and N.

20. The topical composition according to claim 2, wherein the backbone of R.sub.1 and/or R.sub.2 comprises a heteroatom selected from O, S, and N.

Description

DETAILED DESCRIPTION

[0100] The present invention will be better understood and other features will appear in the light of the following non limiting examples.

[0101] A) Example of Preparation of a Peptide According to the Invention: The Myr-PPL-OH

[0102] The Myr-PPL-OH peptide is prepared by peptidic synthesis. Leucine is coupled with a resin via its terminal acid function (with a coupling agent such as DCC (dicyclohexylcarbodiimide)/NHS (N-hydroxysuccinimide) or HBTU (2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate)/HOBT (1-hydroxy-benzotriazole)). Leucine thus protected is reacted with a derivative of proline in the presence of a coupling agent. The same operation is then realized to add the second proline. The latter is thereafter acylated on its amine with an activated derivative of myristic acid (myristoyle chloride for example) in the presence of a base. After precipitation, washing and drying, myristoyl-prolyl-prolyl-leucine product is obtained in a solid form.

[0103] This same synthesis method can be applied to other peptides of formula I according to the invention, for example to the Myr-PPR-OH peptide.

[0104] B) Preparation of a Composition According to the Invention Comprising the Myr-PPL-OH Peptide of Example A).

Starting Materials:

[0105] The pur peptide, synthesized according to the synthesis method explained above; [0106] Excipient: a mixture of fatty esters, chosen to form an oily matrix, for example for forming a composition without water for the further formulation of cosmetic formulation free of water.

Operating Mode:

[0107] The peptide is mixed to the excipient and put under gentle stirring and heating until solubilization and total clarity.

[0108] C) In Vitro Evaluations

[0109] The peptides of the invention have a number of remarkable effects presented below. Peptides prepared according to A) above and dissolved in an excipient were tested in vitro and showed the activities that are presented below.

[0110] 1) ELISA Assays

Protocol

[0111] Normal human fibroblasts (NHF) in culture are contacted with the products to be tested or their excipient (negative control) for 72 h. After the contact, the culture supernatants are removed and the synthesis of dermal macromolecules are estimated by ELISA assays. An estimation of cell viability is performed by Hoechst assay and used to weight the obtained data.

Results

[0112]

TABLE-US-00004 TABLE 4 Collagen I % change/ Significance Compound Concentration control (Student test) Myr-PPA-OH 3 ppm +40 p < 0.05 Myr-PPA-OH 7 ppm +143 p < 0.01 Myr-PPS-OH 3 ppm +70 p < 0.01 Myr-PPS-OH 7 ppm +172 p < 0.01 Myr-PPD-OH 1 ppm +27 p < 0.05 Myr-PPD-OH 3 ppm +57 p < 0.01 Myr-PPD-OH 7 ppm +44 p < 0.01 Myr-PPK-OH 3 ppm +75 p < 0.01 Myr-PPK-OH 4 ppm +68 p < 0.05 Myr-PPK-OH 5 ppm +145 p < 0.01 Myr-PPL-OH 1 ppm +34 p < 0.05 Myr-PPL-OH 3 ppm +59 p < 0.01 Myr-PPL-OH 5 ppm +87 p < 0.01 Myr-PPR-OH 3 ppm +90 p < 0.01 Myr-PPR-OH 4 ppm +163 p < 0.01 Myr-PPR-OH 5 ppm +160 p < 0.01

TABLE-US-00005 TABLE 5 Collagen IV % change/ Significance Compound Concentration control (Student test) Myr-PPA-OH 7 ppm +54 p < 0.05 Myr-PPS-OH 3 ppm +28 p < 0.01 Myr-PPS-OH 7 ppm +42 p < 0.01 Myr-PPD-OH 1 ppm +23 p < 0.01 Myr-PPD-OH 3 ppm +37 p < 0.01 Myr-PPK-OH 3 ppm +37 p < 0.05 Myr-PPK-OH 4 ppm +52 p < 0.01 Myr-PPK-OH 5 ppm +64 p < 0.01 Myr-PPK-OH 6 ppm +57 p < 0.01 Myr-PPL-OH 1 ppm +38 p < 0.01 Myr-PPL-OH 3 ppm +51 p < 0.01 Myr-PPL-OH 5 ppm +83 p < 0.01 Myr-PPL-OH 7 ppm +159 p < 0.01 Myr-PPR-OH 3 ppm +49 p < 0.01 Myr-PPR-OH 4 ppm +64 p < 0.01 Myr-PPR-OH 5 ppm +104 p < 0.01 Myr-PPR-OH 6 ppm +93 p < 0.01

TABLE-US-00006 TABLE 6 Fibronectin % change/ Significance Compound Concentration control (Student test) Myr-PPA-OH 1 ppm +25 p < 0.05 Myr-PPA-OH 7 ppm +60 p < 0.01 Myr-PPS-OH 1 ppm +28 p < 0.01 Myr-PPS-OH 7 ppm +87 p < 0.01 Myr-PPD-OH 1 ppm +53 p < 0.01 Myr-PPD-OH 3 ppm +44 p < 0.01 Myr-PPD-OH 7 ppm +48 p < 0.01 Myr-PPK-OH 3 ppm +32 p < 0.05 Myr-PPK-OH 5 ppm +46 p < 0.01 Myr-PPL-OH 3 ppm +73 p < 0.01 Myr-PPL-OH 5 ppm +41 p < 0.05 Myr-PPL-OH 7 ppm +66 p < 0.01 Myr-PPR-OH 4 ppm +27 p < 0.01

TABLE-US-00007 TABLE 7 Laminin % change/ Significance Compound Concentration control (Student test) Myr-PPA-OH 1 ppm +40 p < 0.05 Myr-PPA-OH 3 ppm +80 p < 0.01 Myr-PPA-OH 7 ppm +143 p < 0.01 Myr-PPS-OH 7 ppm +41 p < 0.01 Myr-PPD-OH 3 ppm +23 p < 0.05 Myr-PPK-OH 1 ppm +34 p < 0.05 Myr-PPK-OH 3 ppm +102 p < 0.01 Myr-PPK-OH 5 ppm +92 p < 0.01 Myr-PPL-OH 1 ppm +29 p < 0.05 Myr-PPL-OH 3 ppm +83 p < 0.01 Myr-PPL-OH 5 ppm +53 p < 0.01 Myr-PPL-OH 7 ppm +41 p < 0.05 Myr-PPR-OH 3 ppm +24 p < 0.01 Myr-PPR-OH 4 ppm +39 p < 0.01

TABLE-US-00008 TABLE 8 Elastin % change/ Significance Compound Concentration control (Student test) Myr-PPA-OH 7 ppm +57 p < 0.05 Myr-PPA-OH 10 ppm +92 p < 0.01 Myr-PPS-OH 3 ppm +60 p < 0.05 Myr-PPS-OH 7 ppm +117 p < 0.01 Myr-PPD-OH 1 ppm +63 p < 0.01 Myr-PPD-OH 3 ppm +65 p < 0.01 Myr-PPD-OH 7 ppm +123 p < 0.01 Myr-PPD-OH 10 ppm +85 p < 0.05 Myr-PPK-OH 3 ppm +46 p < 0.05 Myr-PPL-OH 5 ppm +86 p < 0.05 Myr-PPL-OH 7 ppm +137 p < 0.01 Myr-PPR-OH 5 ppm +81 p < 0.01

[0113] The results show that the peptides according to the invention stimulate the synthesis of collagens I and IV, fibronectin, laminins and elastin on normal human fibroblasts at concentrations of a few ppm and in significant amounts, with a predominant activity for Myr-PPR-OH and Myr-PPL-OH.

[0114] 2) Immunofluorescence Dosages

Protocol

[0115] Normal human fibroblasts (NHF) are cultured for 24 h. The cells are contacted or not with the products to be tested or their excipient at various concentrations for 6 days for the collagen I or 14 days for elastin (DMEMc 5% FCS). The synthesis of collagen I and elastin produced by the cells in the form of extracellular matrix is then quantified by immuno-marking on the fixed layers. A counting of the nuclei labeled with Hoechst is performed in parallel in order to have an estimate of the viability and in order to weight the data.

Results

[0116]

TABLE-US-00009 TABLE 9 Collagen I % change/ Significance Compound Concentration control (U Mann Whitney test) Myr-PPL-OH 3 ppm +68 p < 0.01 Myr-PPL-OH 7 ppm +95 p < 0.01

TABLE-US-00010 TABLE 10 Elastin % change/ Significance Compound Concentration control (U Mann Whitney test) Myr-PPL-OH 2 ppm +183 p < 0.01 Myr-PPL-OH 3 ppm +259 p < 0.01 Myr-PPL-OH 7 ppm +145 p < 0.01 Myr-PPR-OH 2 ppm +148 p < 0.01 Myr-PPR-OH 3 ppm +141 p < 0.01 Myr-PPR-OH 7 ppm +44 p < 0.01

[0117] 3) Keratinocyte Differentiation

[0118] a. Visual Effect

Protocol

[0119] Human keratinocytes are brought to just confluence in KSFMc medium. The contact with the actives and therefore their evaluation is then done in KSFMc medium alone or with calcium (0.8 mm)*. Visual evaluation of differentiation takes place after several days of contact (2, 4, 8 days/3, 5 and 7 for example). * Calcium differentiation allows the creation of link structure between the cells which leads to a better attachment of the basal layers.

Results

[0120]

TABLE-US-00011 Peptide Keratinocyte differenciation Pal-KTTKS - positive control + at 5 ppm Myr-PPL-OH ++ at 5 ppm

[0121] b. Marking of Neutral Lipids with Red Oil

Protocol

[0122] On the same cultures as presented before, a marking of neutral lipids with red oil is realised on the fixed layers. Quantification by image analysis is used to estimate lipid synthesis in keratinocytes. A counter-colouration of the nucleus using Hoechst dye is used to weight the obtained data.

Results

[0123]

TABLE-US-00012 Peptide Concentration % variation Myr-PPL-OH 4 ppm +394 (p < 0.01) 6 ppm +570 (p < 0.01)

[0124] The results show that the peptide Myr-PPL-OH increases the neutral lipids in the human keratinocytes (at the level of the differentiation networks).

[0125] c. Filaggrin 1 and Ceramide 2 Immunolabeling

Protocol

[0126] On the same cultures as those presented before, immunolabeling of filaggrin 1 and ceramides are realised on layers fixed with specific antibodies. Quantification by image analysis is used to estimate the synthesis of these targets in keratinocytes. A counter-colouration of the nucleus using Hoechst dye is used to weight the obtained data.

Results

[0127]

TABLE-US-00013 Filagrin 1 Ceramide 2 Peptide Concentration % variation % variation Myr-PPL-OH 2 ppm +564 (p < 0.01) +137 (nsd) 4 ppm +840 (p < 0.01) +240 (p < 0.01) 6 ppm +172 (p < 0.01) +268 (p < 0.01)

[0128] The results show that the peptide Myr-PPL-OH increases filaggrin 1 and ceramides in the human keratinocytes (at the level of the differentiation networks).

[0129] These results show that the peptide of the invention, and in particular the Myr-PPL-OH, have a pro-differentiating potential on keratinocytes and can be used to improve the properties of the epidermis and skin barrier, in particular for a skin hydration topical treatment.

[0130] A) Galenic

[0131] Different formulations are described below. Additional cosmetic active ingredients, in support and/or in complement of the activity of the active ingredient of invention, can be added to the appropriate phase according to their hydrophobic or hydrophilic nature. These ingredients can be of any class according to their(s) function(s), place of application (body, face, neck, chest, hands, hair, eyelashes, eyebrows, body hair, etc.), the desired final effect, and the targeted consumer, for example antioxidant, moisturizing, nourishing, protective, smoothing, remodeling, volumizing, lipofiling, acting on the radiance of the complexion, anti-spots, anti-dark circles, anti-glycation, slimming, soothing, myo-relaxant, anti-redness, anti-stretch marks, etc. They are mentioned above in the description.

[0132] 1) Cream Form, in Particular an Anti-Aging Day Cream for Face

TABLE-US-00014 Ingredient (INCI name) Weight % Phase A Sorbitan Stearate 3.00 Cyclopentasiloxane (and) Cyclohexasiloxane 2.00 Ethylhexyl Palmitate 3.00 Glyceryl Stearate (and) PEG-100 Stearate 3.00 Ethylhexyl Methoxycinnamate 1.00 Ethylhexyl Dimethyl PABA 1.00 Phase B Demineralised water Qsp 100 Ultrez 10 (Carbomer) 0.40 Phase C Glycerin 5.00 Conservative qs Phase D Peptide according to the invention 3.00 in a fatty excipient Phase E Potassium Sorbate 0.10 Phase F Sodium Hydroxide30% 0.60 Demineralised water 6.00 Phase G Perfume 0.10

Protocol:

[0133] Weigh phase A and heat to 75 C. in a water bath. Weigh phase B and let rise for 20 minutes. Melt phase C until dissolved and add to phase B. Heat phase (B+C) to 75 C. in a water bath. Pour phase A into phase (B+C) under Staro stirring. Extemporaneously, add phase D to phase (A+B+C). At approximately 45 C. add phase E and neutralize with phase F. Mix well. At 35 C., add G. Homogenize well. pH: 6.20.

Examples of Ingredients that can be Added to this Formulation: [0134] CALMOSENSINE: soothing active for sensitive skins marketed by Sederma (WO1998/07744) comprising the lipo-dipeptide Tyr-Arg. It reduces discomfort feelings. [0135] SEBULESS: purifying sebo-regulator ingredient comprising a Syringa vulgaris extract, marketed by Sederma, which mattifies and refreshes complexion, fades the inflammatory blemishes. [0136] PRODIZIA: active ingredient marketed by Sederma (WO2013/046137), comprising an extract of Albizia julibrissin, fighting the signs cutaneous fatigue: dark circles, under eye bags, dull complexion and drawn features, by repairing and protection the skin against the caused by damages of glycation. [0137] PACIFEEL: active ingredient actif marketed by Sederma, comprising a natural extract of the Mirabilis jalapa plant also known as the Marvel of Peru, which alleviates cutaneous discomfort, fades redness of sensitive and reactive skin and strengthens and hydrates the epidermis.

[0138] 2) Gel Form, for Example a Firming Gel for the Body

TABLE-US-00015 Ingredient (INCI name) Weight % Phase A Demineralised water Qsp 100 Ultrez 10 (Carbomer) 0.20 Phase B PEG 400 5.00 Conservatives qs Phase C Dimethicone 4.00 Pemulen TR2 (Acrylates/C10-30 0.20 Alkyl Acrylate Cross Polymer) Phase D Tween 20 (Polysorbate 20) 1.00 Peptide of the invention in a 2.00 fatty excipient Phase E Potassium Sorbate 0.10 Phase F Sodium Hydroxide 30% 0.60 Demineralised water 5.00 Phase G Perfume 0.10

Protocol:

[0139] Disperse Ultrez 10 in water and let swell for 15 minutes. Heat phase B until dissolved and add to phase A. Weigh and mix phase C. Mix phase D and add to phase C; homogenise well. Add phase (C+D) to phase (A+B). Then add phase E. Let swell for 1 hour. Homogenise well. Neutralize with phase F. Finally, add G. pH 6.10.

Examples of Ingredients that can be Added to this Formulation: [0140] AQUALANCE: osmo-protector moisturising active ingredient marketed by Sederma (WO2009/104118) comprising homarine and erythritol. [0141] LEGANCE: anti-aging active marketed by Sederma (WO2013/105047), corresponding to a Zingiber zerumbet Smith extract obtained by CO.sub.2 supercritical in a water-soluble excipient and titrated in zerumbone ingredient. It is a global anti-aging ingredient for legs. It improves their appearance and comfort by reducing water retention, improving microcirculation and refining adipose tissue. [0142] BODYFIT: slimming/firming active ingredient comprising glaucine marketed by Sederma (WO 2004/024695). BODYFIT reduces the appearance of cellulite and helps to improve drainage and water distribution in the tissues. [0143] JUVINITY: active marketed by Sederma (WO 2011/125039) reducing signs of aging on the face and neckline, smoothing wrinkles, densifying and restructuring the dermis.

[0144] 3) Compact Powder Form

TABLE-US-00016 Ingredient (INCI name) Weight % Phase A Talc Qsp 100 Kaolin 2.00 Calcium Stearate 1.00 Mica 4.00 Silica 1.00 Bismuth Oxychloride 2.00 Potassium Sorbate qs Phenoxyethanol qs Phase B Unipure Black LC 989 HLC [CI 77499 (and) Hydrogenated 0.20 Lecithin] Unipure Red LC 381 HLC [CI 77491 (and) Hydrogenated 0.60 Lecithin] Unipure Yellow LC 182 HLC [CI 77492 (and) Hydrogenated 1.00 Lecithin] Covapearl Star Gold 2302 AS [CI 77891 (and) CI 77491 (and) 0.50 Synthetic Fluorphlogopite (and) Triethoxycaprylylsilane] Covapearl Brown 838 HLC [CI 77491 (and) Mica (and) 1.00 Hydrogenated Lecithin) Covapearl Dark Blue 637 [CI 77510 (&) CI 77891 (&) Mica] 0.10 Phase C Crodamol PTIS-LQ-(MV) [Pentaerythrityl Tetraisostearate] 4.00 Peptide of the invention in an oily matrix 3.00 Phase D Perfume 0.30

Protocol:

[0145] Weigh phase A and mix. Weigh phase B and pour into phase A. Pour phase A+B into the blender and blend. Add phase C to A+B in several times and mix each time. Add phase D. Check homogeneity at each step.

Example of Ingredient that can be Added to this Formulation: [0146] VEGESOME MOIST 24: ingredient marketed by Sederma designed for the formulation of moisturizing powder makeup; it is a powder consisting of hollow particles 25 microns (Lycopodium clavatum exins) loaded with an Imperata cylindrica extract having moisturizing properties.

[0147] 4) Alternative Cream Form (Face or Body)

TABLE-US-00017 Ingredient (INCI name) Weight % Phase A Arlacel 170 (Glyceryl Stearate (and) PEG-100 Stearate) 5.50 Abil Wax 2434 (Stearoxy Dimethicone) 3.00 Acetulan (Cetyl Acetate (and) Acetylated Lanolin Alcohol) 1.50 Crodacol C 90 (Cetyl Alcohol) 1.50 Mineral Oil 3.00 Shea Butter 5.00 Unsaponifiable Shea 1.00 Parsol MCX (Ethylhexyl Methoxicinnamate) 3.50 Phase B Demineralised Water Qs 100 Phase C Carbopol 940 (Carbomer) 0.20 Phase D Demineralised Water 2.00 Triethanolamine 99% 0.20 Phase E Propylene Glycol 0.10 Mixed Parabens Phase F Sodium Hydroxide 30% 5.00 Demineralised Water qs Phase G Peptide of the invention in a lipophilic medium 2.00

Protocol:

[0148] Weigh phase A and heat to 75 C. in a water bath. Weigh phase B and let swell for 20 minutes. Melt phase C until dissolved and add to phase B. Heat phase (B+C) to 75 C. in a water bath. Pour phase A into phase (B+C) under Staro stirring. Extemporaneously, add phase D to phase (A+B+C). At approximately 45 C. add phase E and neutralize with phase F. Homogenise well. At 35 C., add G. Homogenise well. pH: 6.20.

Examples of Ingredients that can be Added to this Formulation: [0149] SUBLISKIN: active ingredient marketed by Sederma (WO2009/055663) that moisturizes and smooths the skin while allowing it to resist to external aggressions. [0150] VENUCEANE: active marketed by Sederma (WO2002/066668) comprising a Thermus thermophiles biotechnological extract, that prevents visible signs of photo-aging (spots, wrinkles, dryness . . . ), protects cell structures from damages caused by UV and strengthens skin integrity. [0151] KOMBUCHKA: active ingredient acting on complexion marketed by Sederma (WO2004/012650). [0152] INTENSLIM: slimming active ingredient marketed by Sederma (WO2013/105048) corresponding to a synergistic combination of extracts obtained by Globularia cordifolia plant cell culture, Zingiber zerumbet Smith titrated in zerumbone and vegetable caffeine obtained by supercritical CO.sub.2 extraction.