TETRAPEPTIDES, COMPOSITIONS COMPRISING THEM, AND THEIR COSMETIC USE

Abstract

They have the general Formula X-(Xaa).sub.nLE(Xaa).sub.m-Z wherein Xaa is selected from L, K, E and D, either n=2 and m=0, or n=1 and m=1, at the N-terminal end X being selected from H, —CO—R.sup.1, —SO.sub.2-R.sup.1 or a biotinoyl group, at the C-terminal end Z being selected from OH, OR.sup.1, NH.sub.2, NHR.sup.1 or NR.sup.1R.sup.2, and R.sup.1 and R.sup.2 being selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy, saccharide and aryloxy, said group having from 1 to 24 carbon atoms. Preferred peptide sequences are X-LKLE-Z and X-ELED-Z. These tetrapeptides stimulate the synthesis of molecules constituting the ECM, in particular collagen 1 and 4, hyaluronic acid and fibronectin, and can be used for a cosmetic treatment, in particular anti-aging, anti-wrinkle and fine lines, to improve the skin mechanical properties, to increase skin density and volume, hydration, and/or to fight against stretch marks, and skin sagging.

Claims

1. A tetrapeptide of Formula 1:
X-(Xaa).sub.nLE(Xaa).sub.m-Z  (SEQ ID NOS: 6 to 39) wherein: Xaa is an amino acid chosen from L, K, E and D, the Xaa being chosen independently of each other; either n=2 and m=0, or n=1 and m=1; at the N-terminal X chosen from H, —CO—R.sup.1, —SO.sub.2—R.sup.1 or a biotinoyl group; at the C-terminal Z end chosen from OH, OR.sup.1, NH.sub.2, NHR.sup.1 or NR.sup.1R.sup.2; and R.sup.1 and R.sup.2 being, independently of each other, chosen from an alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfured, the group having from 1 to 24 carbon atoms and optionally having in its backbone one or more heteroatoms O, S and/or N.

2. The tetrapeptide according to claim 1, selected from X-LLLE-Z (SEQ ID NO: 6), X-LKLE-Z (SEQ ID NO: 7), X-LELE-Z (SEQ ID NO: 8), X-LDLE-Z (SEQ ID NO: 9), X-KKLE-Z (SEQ ID NO: 10), X-KLLE-Z (SEQ ID NO: 11), X-KELE-Z (SEQ ID NO: 12), X-KDLE-Z (SEQ ID NO: 13), X-EELE-Z (SEQ ID NO: 14), X-ELLE-Z (SEQ ID NO: 15), X-EKLE-Z (SEQ ID NO: 16), X-EDLE-Z (SEQ ID NO: 17), X-DDLE-Z (SEQ ID NO: 18), X-DLLE-Z (SEQ ID NO: 19), X-DKLE-Z (SEQ ID NO: 20), X-DELE-Z (SEQ ID NO: 21), X-LLEL-Z (SEQ ID NO: 22), X-LLEK-Z (SEQ ID NO: 23), X-LLEE-Z (SEQ ID NO: 24), X-LLED-Z (SEQ ID NO: 25), X-KLEK-Z (SEQ ID NO: 26), X-KLEL-Z (SEQ ID NO: 27), X-KLEE-Z (SEQ ID NO: 28), X-KLED-Z (SEQ ID NO: 29), X-ELEE-Z (SEQ ID NO: 30), X-ELEL-Z (SEQ ID NO: 31), X-ELEK-Z (SEQ ID NO: 32), X-ELED-Z (SEQ ID NO: 33), X-DLED-Z (SEQ ID NO: 34), X-DLEL-Z (SEQ ID NO: 35), X-DLEK-Z (SEQ ID NO: 36) and X-DLEE-Z (SEQ ID NO: 37).

3. The tetrapeptide according to claim 1 or 2, selected from X-LKLE-Z (SEQ ID NO: 7) or X-ELED-Z (SEQ ID NO: 33).

4. The tetrapeptide according to claim 1, wherein the group comprises 3 to 24 carbon atoms.

5. The tetrapeptide according to claim 1, wherein X is an acyl group —CO—R.sup.1 and at the C terminal end Z is a group selected from OH, OMe, OEt and NH.sub.2.

6. The tetrapeptide according to claim 1, wherein the acyl group CO—R.sup.1 is selected from an octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl and lipoyl.

7. The tetrapeptide according to claim 1, wherein Z is OH.

8. The tetrapeptide according to claim 1, corresponding to the Pal-LKLE-OH (SEQ ID NO: 38) or the Pal-ELED-OH (SEQ ID NO: 39).

9. A cosmetic composition comprising at least one tetrapeptide according to claim 1 and a physiologically acceptable medium.

10. The composition according to claim 9, wherein the amount of at least one tetrapeptide is between 10-7% and 20% relative to the total weight of the composition.

11. The composition according to claim 9, comprising at least one additional active ingredient selected from compounds of vitamin B3, niacinamide, tocopherol, retinoid compounds, hexamidine, α-lipoic acid, resveratrol, DHEA, hyaluronic acid and one or more cosmetic peptides.

12. The composition according to claim 9, comprising a mixture of Pal-GHK and Pal-GQPR, and/or the peptide Ac-YR-hexadecyl ester.

13. The composition according to claim 9, constituting an active ingredient for the formulation of a final composition intended for a consumer.

14. A non-therapeutic cosmetic method of improving general condition of the skin and/or its appendages and treating imperfections of the skin and/or its appendages, the method comprising contacting the skin and/or its appendages with at least one tetrapeptide according to claim 1.

15. The method according to claim 14, wherein the contacting is topical.

16. The method according to claim 14, wherein the method is for anti-aging.

17. The method according to claim 14, wherein the method is for one or more of: treating wrinkles and fine lines; improving mechanical properties of the skin which include firmness, tone, elasticity, and/or flexibility; increasing the density and volume of the skin by volumizing, plumping and/or restructuring; preventing or treating stretch marks; preventing or treating skin sagging; preventing or treating a loss of skin hydration; and improving the uniformity and radiance of the complexion.

Description

DETAILED DESCRIPTION

[0099] The present invention will be better understood in the light of the following description of an embodiment and of in-vitro tests.

[0100] A—Example of Synthesis of Tetrapeptides According to the Invention: The Pal-LKLE-OH (SEQ ID No 38) and the Pal-ELED-OH (SEQ ID No 39)

[0101] The Pal-LKLE-OH is prepared by peptidic synthesis. A N-protected glutamic acid is attached to a resin via its terminal acid function. The amine function is deprotected and then the glutamic acid-resin is reacted with a leucine derivative in the presence of a coupling agent (for example DCC (diclyclohexylcarbodiimide)/NHS (N-hydroxysuccinimide) or HBTU (2-(1H-benzotriazole)-1-yl)-1, 1, 3, 3-tetramethyluronium hexafluorophosphate)/HOBT (1-hydroxy-benzotriazole), then the same deprotection and coupling operations are repeated to add the lysine, the leucine and palmitic acid. The peptide is then cleaved from the resin in an acidic medium and after precipitation, washing and drying, the palmitoyl-leucyl-lysyl-leucyl-glutamic acid product is obtained in solid form.

[0102] This same synthetic process can be applied to obtain the le Pal-ELED-OH, optionally in the salt form.

[0103] The tetrapeptides according to the invention can also be prepared biotechnologically, via a microorganism capable of at least partially producing it.

[0104] B—Example of Preparation of a Composition According to the Invention Comprising the Tetrapeptide Pal-LKLE-OH and/or the Pal-ELED-OH of Example a

[0105] Starting Materials: [0106] the pure peptide(s), synthesized according to the synthesis process explained above. [0107] excipient: mixture of fatty esters, chosen to form an oily matrix, for example intended to form an anhydrous composition for the subsequent formulation of anhydrous cosmetic compositions.

[0108] Protocol: a selected amount of one of the two peptides is mixed with the excipient and placed under gentle stirring and heating until solubilization and complete clarity.

[0109] In a particular example 1200 ppm of one of the peptides Pal-LKLE-OH (SEQ ID No 38) or Pal-ELED-OH (SEQ ID No 39) is mixed with the excipient to form an active ingredient used in the below galenic part D).

[0110] C—In-Vitro Evaluations

[0111] The peptides according to the invention exhibit remarkable effects presented below. The two peptides prepared according to A) above and dissolved in an excipient were tested in-vitro and showed activities which are presented below.

[0112] 1—ELISA Assays

[0113] Protocol

[0114] Normal human fibroblasts (NHF) in culture are brought into contact with the products to be tested or their excipient (negative control) for 72 h. At the end of the contact, the culture supernatants are removed, and the syntheses of the dermal macromolecules are estimated by ELISA assays. An estimate of cell viability is carried out by Hoechst assay to weight the obtained data. Collagen I is evaluated via the PIP assay (carboxy-terminal propeptide of procollagen type I) which is a peptide fragment resulting from the enzymatic degradation of procollagen when the latter is excreted outside the fibroblast (therefore in the culture medium where the assay is carried out).

[0115] Results

TABLE-US-00001 TABLE 1 Pal -LKLE-OH Pal-ELED-OH (Concentrations (Concentrations of 5 to 15 ppm) Significance of 2 to 3 ppm) Significance Collagen I (PIP) +81% p < 0.01 +42% p < 0.05 Fibronectine +48% p < 0.01 +70% p < 0.01 Decorine +21% p < 0.01 +69% p < 0.05 Collagen IV / +42% p < 0.01 Hyaluronic acid / +28% p < 0.05

[0116] 2—Immunofluorescence Assays

[0117] Protocol

[0118] Normal human fibroblasts (NHF) are cultured for at least 24 hours in fibroblast growth medium containing serum. Once confluence was reached, the cells are seeded and the actives and corresponding controls diluted in a culture medium are added. At the end of a five day incubation period, the supernatant is removed, the cells are washed with PBS and fixed. The cells are then incubated with the primary Fibrillin 1 monoclonal antibody (11C1.3) (Thermo Fisher) diluted in blocking buffer at a concentration of 1:200. The cells are incubated. The primary antibody is removed and the cells are washed with PBS. The secondary antibody was added at a dilution of 1:1000 in blocking buffer, then removed and the cells are washed with PBS. The formation of Fibrillin 1 by the cells is visualized using a fluorescence microscope. The obtained images are analyzed using an image processing software assigning a numerical value to the coverage density.

[0119] Results

TABLE-US-00002 TABLE 2 Pal-LKLE-OH Pal-ELED-OH (10 ppm) (4 ppm) Fibrillin 1 (significance) +81% (p < 0.05) +97% (p < 0.05)

[0120] All these results show the interest of two tetrapeptides according to the invention for a cosmetic treatment based in particular on the stimulation of the synthesis of collagens I and IV, of fibronectin, of decorin, of hyaluronic acid, and of Fibrillin 1 by the fibroblasts of the ECM, at concentrations of a few ppm.

[0121] 3—Mass Spectrometry Analysis (LC-MS/MS)—Pal-ELED-OH (SEQ ID No 9)

[0122] Protocol Human dermal fibroblasts (HDF) are cultured with or without the peptide according to the invention (control) in n=3. The cells are cultured normally for five days in serum supplemented medium, then for two additional days in serum-free medium (culture of seven days in total). The cellular medium (secretome) is collected and the matrix separated from the cells with EDTA. The secretome and matrisome are kept for LC-MS/MS analysis. The cells are saved for future analysis. The secretome and matrisome compartments are pooled and processed as single samples.

[0123] Mass spectrometry is used to determine the total amount of certain proteins identified in the secretome and matrisome in the presence of the peptide of the invention and which are absent from the control following the day 7 of incubation. The proteins are denatured (in urea), reduced (in dithiothreitol) and mechanically dissociated (using ultrasound) prior to overnight digestion with the SMART Digest™ Trypsin Kit (Thermo Fisher).

[0124] The samples are analyzed on an UltiMate® 3000 rapid separation liquid chromatograph coupled to a Q Exactive™ Quadrupole-Orbitrap™ hybrid mass spectrometer: 200 ng injected at an analysis time of 90 minutes per sample.

[0125] Protein quantification is performed using Progenesis QI and protein identification using Mascot v2.5.1. Normalized protein concentrations are compared between the peptide and the control. Statistical analysis is performed with the Progenesis QITM software using an ANOVA test between-samples.

[0126] Results [0127] Nidogen-1 stimulation (p<0.05); protein involved in the basement membrane. [0128] Decorine stimulation (0.05<p<0.1); confirms the MEC ELISA results given above.

[0129] These results confirm the interest of the peptide having the peptidic sequence ELED in an anti-aging cosmetic axis linked to the constituents of ECM. [0130] SOD3 stimulation (0.05<p<0.1) (codee A0A140V-JU8); SOD3 is an antioxidant superoxide dismutase. [0131] RAD23A stimulation (0.05<p<0.1); RAS23A is a protein involved in the repair of DNA mutations (excision/repairing system) and the targeting of ubiquitinylated proteins toward the proteasome.

[0132] These results also confirm the interest of the peptide according to the invention having the ELED peptidic sequence in an anti-aging cosmetic axis also linked to cellular protection/repairing.

[0133] D—Galenics

[0134] Different formulations are described below. Additional cosmetic active ingredients, supporting and/or supplementing the activity of the active ingredient according to the invention, can be added in the appropriate phase depending on their hydrophobic or hydrophilic nature. These ingredients can be of any category according to their role(s), the place of application (body, face, neck, bust, hands, hair, eyelashes, eyebrows, body hair, etc.), the desired final effect and the targeted consumer, for example antioxidant, hydrating, nourishing, protective, smoothing, remodeling, volumizing (lipofiling), acting on complexion radiance, treating spots, concealer, anti-glycation, slimming, soothing, myo-relaxing, anti-redness, anti-stretch marks, etc. Examples are mentioned above in the description.

[0135] The formulas described below include an active ingredient based on a tetrapeptide according to the invention as described in point B above, comprising 1200 ppm of tetrapeptide. The formulas could also contain a mixture of these two tetrapeptides according to the invention formulated from an active ingredient comprising them in equal proportions or not. These formulas are given as a guide and may contain higher percentages of the active ingredient according to the invention.

[0136] 1) Cream Form, for Example for an Anti-Aging Day or Night Cream for the Face

TABLE-US-00003 TABLE 3 Raw material INCI name Role % Part A: H.sub.2O / / qsp 100 Carbopol ™ Ultrez 10 Carbomer Thickener/Gelling agent 0.30 Part B: Brij S2-SS-(RB) ™ Steareth-2 Emulsifier 0.40 Brij S10-SO-(RB) ™ Steareth-10 Emulsifier 1.20 Crodafos CES-PA-(RB) ™ Cetearyl Alcohol (and) Emulsifier/conditionner 4.00 Dicetyl Phosphate (and) Ceteth-10 Phosphate Crodacol CS90-PA-(RB) Cetearyl Alcohol Emollient 1.50 Laurocapram Laurocapram Emollient 2.50 Crodamol ™ AB-LQ-(RB) C12-15 Alkyl Benzoate Emollient 1.50 Crodamol ™ OSU-LQ-(JP) Diethylhexyl Succinate Emollient 7.00 Part C: Glycerin Glycerin Humectant 2.50 Octanediol Caprylyl Glycol Humectant/Emollient 0.50 Part D: Phenoxyethanol Phenoxyethanol Preservative qs Part E: Potassium sorbate Potassium Sorbate Preservative qs Part F: H.sub.2O / / 4.00 NaOH 30% Sodium Hydroxide pH adjuster 0.40 Part G: Ingredient comprising the / Active 3.00 tetrapeptide(s) according to the invention

[0137] Examples of Additional Active Ingredients:

[0138] Supplementing the Activity: [0139] 1—an ingredient acting on the skin elastic properties, such as: [0140] IDEALIFT™, marketed by Sederma, comprising the N-acetyl-Tyrosyl-Arginyl-O-hexadecyl ester lipopeptide, fighting against facial flaccidity and improving gravity resistance through elastin stimulation. [0141] BPEL™, marketed by Sederma, comprising the Pal-VGVAPG (SEQ ID No 3) peptide. [0142] 2—an ingredient actif more specifically on epiderm, such as: [0143] CRYSTALIDE™, marketed by Sederma, comprising the Pal-KTFK (SEQ ID No 48) peptide, vectorised in the epiderm thanks to a oil-wax-surfactants and water microemulsion in which the peptide is solvated, exerting a bio-harmonic action in the epidermis by regulating epigenetic and inflammatory phenomena, and by harmonizing the process of skin maturation. [0144] 3—a moisturizing/smoothing ingredient, such as: [0145] OPTIMHYAL™, marketed by Sederma, contains oligosaccharides of acetylated glucuronic acids having a structure similar to fragments of hyaluronic acid. [0146] 4—a sebum-regulating ingredient, such as: [0147] SEBULESS™, marketed by Sederma, comprising a Syringa vulgaris extract produced by in vitro plant cell culture, which is a purifying sebum regulator, that mattifies and refreshes the complexion, and blurs imperfections. [0148] 5—an ingredient acting on the harmful effects of blue light, such as: [0149] SYNCHROLIFE™, marketed by Sederma, comprising the Pal-GQPR peptide (SEQ ID No 2), chrysin and a rosemary extract; rebalances the production of key molecules of the circadian cycle (opsin5, period2, melatonin) and ensures a reinforced repairing metabolism (energy, antioxidant, anti-inflammatory and repair of the skin matrix).

[0150] Reinforcing the activity: an ingredient acting on the synthesis of ECM macromolecules, such as: MATRIXYL™ (based on the Pal-KTTKS (SEQ ID No 1) peptide, MATRIXYL 3000™ (based on a mixture of the Pal-GQPR (SEQ ID No 2) and Pal-GHK peptides), MATRIXYL synthe'6 ™ (based on the KMO.sub.2K peptide) and/or MATRIXYL Morphomics™ (based on the Pal-K(P)HG peptides), that are marketed by Sederma. [0151] PORETECT™, marketed by Sederma, comprising a combination of flax and celery seed extracts titrated in cylolinopeptides and senkyunolides, which brings firmness, tone and density to the skin, thus reinforcing the maintening structures of skin pores which sag with the age. [0152] FEMINAGE™, marketed by Sederma, comprising an Engelhardia chrysolepis extract titrated in astilbin, a glycosylated flavonoid, offering elastic and firming properties to the skin, particularly in postmenopausal women.

[0153] 2) Aqueous Mild Serum Form

TABLE-US-00004 TABLE 4 Raw material INCI name Role % Part A: H.sub.2O / / qsp 100 Potassium sorbate Potassium Sorbate Preservative 0.10 Part B: Glycerin Glycerin Humectant 5.00 Phenoxyethanol Phenoxyethanol Preservative 0.80 Part C: Cromollient ™ SCE Di-PPG-2 Myreth-10 Adipate Emollient 1.20 VisiaOptima ™ SE Sodium Polyacrylate (and) Rheology modifier 1.00 Ethylhexyl Cocoate (and) and emulsion stabilizer PPG-3 Benzyl Ether Myrisate (and) Polysorbate 20 Part D: H.sub.2O / / 0.80 NaOH 30% Sodium Hydroxide pH adjuster 0.08 Part C: Ingredient comprising / Active 3.00 the tetrapeptide(s) according to the invention

[0154] Examples of Additional Active Ingredients, Suplementing the Activity: [0155] 1—an anti-aging ingredient, such as: [0156] SENESTEM™, marketed by Sederma, comprising Plantago lanceolata plant cells obtained by in-vitro cell culture, improving the viscoelastic properties of the skin and lightening the senescence pigmentary spots. [0157] 2—an antioxidant ingredient, such as: [0158] MAJESTEM™, marketed by Sederma, based on Leontopodium alpinum plant cells titrated in leontopodic acid, obtained by in-vitro cell culture, neutralizing oxydative stress (pollution, UVB radiation) and restoring cutaneaous tense.

[0159] 3) Gel Form

TABLE-US-00005 TABLE 5 Raw material INCI name Role % Part A: H.sub.2O / / qsp100 Carbomer / Rheology 0.40 modifier Part B: Glycerin Glycerin Humectant 7.00 Phenoxyethanol Phenoxyethanol Conservateur 0.80 Part C: H.sub.2O / / 3.00 NaOH 30% Sodium Hydroxide pH adjuster 0.30 Part D: Tween ™ 20 Polysorbate 20 Emulsifier 0.50 Cromollient ™ SCE Di-PPG-2 Myreth-10 Adipate Emollient 1.00 Covi-ox ™ Tocopherol (and) Helianthus Antioxidant 0.40 Annuus (Sunflower) Seed Oil Part E: Ingredient comprising / Active 3.00 the tetrapeptide(s) according to the invention

[0160] Examples of Additional Active Ingredients, Supplementing the Activity: [0161] 1—an antipollution ingredient, such as: [0162] CITYSTEM™, marketed by Sederma, based on Marrubium vulgare plant cell having a high Forsythoside B concentation, produced by in-vitro plant cell culture, used againt pollution attacks, makes the skin soft and smooth, refines skin texture, reduces blackhead visibility, leaving the skin radiant and purified. [0163] 2—a calming ingredient for sensitive skin, such as: [0164] PACIFEEL™, marketed by Sederma, comprising a Mirabilis Jalapa plant extract. [0165] 3—a moisturizing ingredient such as: [0166] AQUALANCE™, marketed by Sederma, an osmoprotective moisturizer composed of homarin and erythritol.

[0167] 4) Gel Form to Make a Spray Mask

TABLE-US-00006 TABLE 6 Raw material INCI name Role % Part A: H.sub.2O / / qsp100 Hydrotriticum PVP PE ™ Aqua (and) Hydrolyzed Wheat Filmogen agent 3.00 Protein/PCP Crosspolymer Volarest ™ FL Acrylates/Beheneth-25 Rheology 2.30 Methacrylate Copolymer modifier Potassium sorbate Potassium Sorbate Preservative Part B: Glycerin Glycerin Humectant 5.00 Phenoxyethanol Phenoxyethanol Preservative 0.80 Part C: Crovol ™ A70 PEG-60 Almond Glycerides Emollient 1.00 Ethanol Ethanol Solvent 5.00 Covi-ox ™ Tocopherol (and) Helianthus Antioxidant 0.20 Annuus (Sunflower) Seed Oil Part D: H.sub.2O / / 2.50 NaOH 30% Sodium Hydroxide pH adjuster 0.25 Part E: Ingredient comprising the Active 3.00 tetrapeptide(s) according to the invention

[0168] Examples of Additional Active Ingredients, Suplementing the Activity: [0169] 1—an ingredient acting on complexion radiance, such as: [0170] EVERMAT™, marketed by Sederma, comprising a combination of an Enantia chlorantha extract rich in protobberberins and oleanolic acid, decreasing pore size and shine, refining acne-prone skin texture. [0171] 2—an ingredient with revitalizing properties, such as: [0172] Fruitliquid™ Kumquat™, marketed by Crodarom.

[0173] 5) Cream Form, for a Make-Up Base

TABLE-US-00007 TABLE 7 Raw material INCI name Role % Part A: H.sub.2O / / qsp 100 Volarest ™ FL Acrylates/Beheneth-25 Methacrylate Rheology 0.90 Copolymer modifier Part B: Arlacel ™ 2121 Sorbitan Stearate (and) Sucrose Emulsifier 4.50 Cocoate) Part C: Pentylene glycol Pentylene Glycol Humectant 5.00 Phenoxyethanol Phenoxyethanol Preservative 0.80 Part D: Crodamol ™ SSA Decyl Isostearate (and) Isostearyl Emollient 2.00 Isostearate Crodamol ™ TN Isotridecyl Isononanoate Emollient 2.00 Crodamol ™ AB C12-C15 Alkyl Benzoate Emollient 1.50 Crodamol ™ GTEH Triethylhexanoin Emollient 3.00 Covi-ox ™ Tocopherol (and) Helianthus Annuus Antioxidant 0.10 (Sunflower) Seed Oil Part D: Potassium sorbate Potassium Sorbate Preservative 0.10 Part E: H.sub.2O / / 2.50 NaOH 30% Sodium Hydroxide pH adjuster 0.25 Part E: Ingredient comprising Active 3.00 the tetrapeptide(s) according to the invention

[0174] Examples of Additional Active Ingredients, Suplementing the Activity: [0175] 1—An ingredient for treating eye dark circles and contour, such as: [0176] HALOXYL™, marketed by Sederma, an association of two matrikins, the Pal-GHK and the Pal-GQPR (SEQ ID No 2) with N-hydroxysuccinimide and a flavonoid, chrysin.

[0177] EYELISS™, marketed by Sederma, combining three components methyl chalcone hesperidin, the Valyl-Tryptophan peptide (VW) and the Pal-GQPR (SEQ ID No 2) lipopeptide.

[0178] PRODIZIA™, marketed by Sederma, comprising an Albizia julibrissin plant extract, favorising the reduction of visible of fatigue: dark circles, under eyes bags, dull complexion and drawn features by repairing and protecting skin from damages caused by glycation. [0179] 2—anti-wrinkles/anti-aging ingredient comprising peptide(s) such as: MATRIXYL 3000™ MATRIXYL synthe'6™ and/or MATRIXYL Morphomics™ marketed by Sederma. [0180] 3—an ingredient acting on skin radiance such as Amberstem™, marketed by Sederma, which embellishes olive carnation skins, derived from the cell culture of Buddleja davidii leaves (butterfly tree), acting on skin radiance by reducing inflammatory hyperpigmentation, dull complexion and redness while strengthening skin barrier and hydration.