PEPTIDE BASED COSMETIC OR DERMATOLOGICAL TREATMENT OF THE SKIN AND ITS APPENDAGES

Abstract

The treatment according to the invention provides the use of at least one peptide having the general Formula X-(Xaa)nK*TTK*X′aa-(Xaa)m-Z for a non-therapeutic cosmetic treatment of keratinous tissues of the skin and of its appendages, where X, Xaa, n, K*, X′aa, m and Z are as defined. A preferred peptide is the Pal-KTTKS.

Claims

1. Use of at least one peptide of the following general Formula 1:
X-(Xaa).sub.nK*TTK*X′aa-(Xaa).sub.m-Z for a non-therapeutic cosmetic treatment of keratinous tissues of the skin and of its appendages, wherein in the general Formula 1: K* is selected from lysine, hydroxylysine, ornithine, diaminobutyric acid or diaminopropionic acid or their formylated, acetylated, trifluoroacetylated, methanesulfonylaed or succinylated derivatives, both K* being identical or different; (Xaa)n and (Xaa)m corresponding independently of one another to a sequence of n or m amino acids Xaa selected independently of one another from Gly, Ala, Pro, Val, Leu, Ile and Phe, with n and m being integers which can be equal or different and comprised between 0 and 5; X′aa is selected from threonine and serine; At the N-terminal end X is selected from H, —CO—R.sup.1, —SO.sub.2—R.sup.1 or a biotinoyle group; At the C-terminal end Z is 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, independently of one another, selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which can be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfurated, said group having from 1 to 24 carbon atoms and the possibility of having in its backbone one or more O, S and/or N heteroatoms.

2. The use according to claim 1, wherein the treatment is adapted to preserve, protect and/or improve the condition of the epidermis by strengthening the skin barrier function and harmonizing the natural process of epidermal maturation.

3. The use according to claim 1, wherein the treatment is adapted to protect the skin and its appendages from molecules and aggressions of the external environment including the defense against bacteria, inflammation, and radiations.

4. The use according to claim 1, wherein the treatment is adapted to improve the hydration of the upper part of the epidermis by reducing the transepidermal water loss (TEWL).

5. The use according to claim 1, wherein the treatment is adapted to treat the epidermal scars.

6. The use according to claim 1, wherein the treatment is adapted to treat epidermal acne scars.

7. The use according to claim 1, wherein the treatment is adapted to beautify nails, hair and body hair including eyelashes and eyebrows.

8. The use according to claim 3, wherein the treatment is adapted to fight against the microorganisms of acne and/or of dandruff state.

9. The use according to claim 1, wherein the at least one peptide is used in a vectorized form, being bound, incorporated or adsorbed on/to macro-, micro-, or nano-particles in the form micro- or nano-emulsions, or adsorbed on powdery organic polymers, talcs, bentonites, spores or exins and other inorganic or organic supports.

10. The use of at least one peptide having the following general Formula 1:
X-(Xaa)nK*TTK*X′aa-(Xaa)m-Z wherein in the general Formula 1: K* is selected from lysine, hydroxylysine, ornithine, diaminobutyric acid or diaminopropionic acid or their formylated, acetylated, trifluoroacetylated, methanesulfonylaed or succinylated derivatives, both K* being identical or different; (Xaa)n and (Xaa)m corresponding independently of one another to a sequence of n or m amino acids Xaa selected independently of one another from Gly, Ala, Pro, Val, Leu, Ile and Phe, with n and m being integers which can be equal or different and comprised between 0 and 5; X′aa is selected from threonine and serine; At the N-terminal end X is selected from H, —CO—R.sup.1, —SO.sub.2—R.sup.1 or a biotinoyle group; At the C-terminal end Z is 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, independently of one another, selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which can be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfurated, said group having from 1 to 24 carbon atoms and the possibility of having in its backbone one or more 0, S and/or N heteroatoms. for the preparation of a composition for treatment of keratinous tissues of the skin and of its appendages.

11. The use according to claim 1, wherein K* is lysine or ornithine.

12. The use according to claim 1, wherein X′aa is serine.

13. The use according to claim 1, wherein n and m are independently of one another 0 or 1 or 2.

14. The use according to claim 1, wherein the peptide is either modified at the N-terminal position or at the C-terminal position.

15. The use according to claim 1, wherein R.sup.1 and/or R.sup.2 is an alkyl chain of 1 to 24 carbon atoms.

16. The use according to claim 1, wherein R.sup.1 and/or R.sup.2 is an alkyl chain of 3 to 24 carbon atoms.

17. The use according to claim 1, wherein X is a CO—R.sup.1 acyl group and Z is selected from OH, OMe, OEt and NH.sub.2.

18. The use according to claim 1, wherein the peptide is the Pal-KTTKS (SEQ ID NO 1).

19. Method of skin treatment comprising topical application to a skin in need thereof of an effective amount of the peptide as defined in claim 1 wherein the treatment is antimicrobial (antibacterial or antifungal), and/or anti-inflammatory, said treatment being suitable for soothing sensitive and irritated skin and/or for treating acne, psoriasis, dermatitis and eczema.

Description

DETAILED DESCRIPTION

[0080] The present invention will be better understood in the light of the description which will follow of an embodiment and of in vitro and in vivo tests.

A) Example of Preparation of the Pal-KTTKS Peptide (SEQ ID NO 1) According to the Invention

[0081] The Pal-KTTKS peptide is prepared by peptide synthesis. A serine is coupled with a resin via its terminal acid function (with a coupling agent, for example DCC (diclyclohexylcarbodiimide)/NHS (N-hydroxysuccinimide) or HBTU (2-(1H-benzotriazol-1-yl)-1, 1, 3, 3-tetramethyluronium hexafluorophosphate)/HOBT (1-hydroxy-benzotriazole)). The serine thus protected is then reacted with a lysine derivative in the presence of a coupling agent, then the same operation is carried out to add two threonines, then the same operation to add the second lysine. The latter is then acylated on its amine function with an activated palmitic acid derivative (palmitoyl chloride for example) in the presence of a base. The peptide chain is cleaved from the resin in an acidic medium and after precipitation, washing and drying. The product palmitoyl-lysyl-threonyl-threonyl-lysyl-serine is obtained in solid form.

B) Example of Preparation of a Cosmetic Active Ingredient According to the Invention Comprising the Pal-KTTKS (SEQ ID NO 1)

[0082] The Pal-KTTKS peptide is amphiphilic, the Pal chain being hydrophobic and the peptide part being hydrophilic. The peptide, for example at 100 ppm, is solubilized in a water/glycol matrix with suitable surfactants.

[0083] The Matrixyl® commercial ingredient comprising Pal-KTTKS (Palmitoyl Pentapeptide-4) can be used for implementing the invention.

C) Efficacy Tests

[0084] They were carried out on the preferred peptide according to the invention, the Pal-KTTKS, in solution in an inert solvent (ethanol), at concentrations recommended for use on the skin.

[0085] The in vitro tests below were performed on epidermis cells, the normal human keratinocytes (NHK). A test was carried out on a culture of the bacterium Propionibacterium acnes.

[0086] The Various Test Methods Used are Described Below.

[0087] Molecular Biology Study on NHK Culture

[0088] Principle: in this test, confluent keratinocytes are brought into contact with the peptide according to the invention for 24 hours. The cells are then frozen to dryness and their RNAs are extracted, converted into DNA, then analyzed by qRT-PCR (“Quantitative real time reverse transcription polymerase chain reaction”). The results are expressed as an expression ratio between the treated case and the control case. A ratio greater than 1.5 is as an induction of gene expression (+50% compared to the control). A study of variances and a Student's t test are carried out for judging the significance of the results (n=4 for each condition).

[0089] Study by Immune Enzymatic Assay on NHK Culture

[0090] Principle: NHKs in culture and at confluence are brought into contact with the peptide according to the invention (or its solvent) for 24 hours in a medium allowing their survival. Then the cell layers are irradiated with UVB in a physiological buffer and again brought into contact with the products to be tested for 24 hours. At the end of this incubation, the culture media are assayed by ELISA to know the amounts of pro-inflammatory mediators produced by these cells in response to irradiation. The results are compared to the control. A cell respiration test is conducted on the fixed mat to assess the number of cells and standardize the results. A study of variances and a Student's t test are carried out for judging the significance of the results.

[0091] Study Using DNA Microarray Technology (DNA-Array) on NHK Culture

[0092] Principle: the peptide according to the invention (7 ppm) is brought into contact for 24 or 48 hours with confluent NHKs (vs. control case). Then the NHK mats are rinsed, and the cells are crushed to extract their mRNA. These mRNAs are then converted into DNA sequences which are analyzed after depositing on DNA chips and amplification by a method like QRT-PCR. The mRNA variations due to the peptide are compared to the control case (peptide solvent). The results are expressed as an expression ratio between the treated case and the control case. A ratio greater than 1.5 is as an induction of gene expression (+50% compared to the control).

[0093] Liquid Chromatography/Mass Spectrometry (LC-MS/MS) Study on NHK Culture

[0094] Principle: the same culture protocol as for the DNA-Array is used but with a longer culture time (7 days) because the protein productions take longer to be able to be detected with this method in LC-MS/MS. The peptide concentration applied to the cells is 5 ppm (vs. control case). The culture medium of the NHK (n=3) is changed every 3 days. At the end of this contact, the cells are lysed for extracting the proteins and to analyze them in the form of ground material by a method combining the action of a protease on the ground material, the separation of the fragments by liquid chromatography coupled with mass spectrometry, and then the identification and concentration of pre-existing proteins according to the nature and quantity of the fragments obtained (LC-MS/MS). To carry out LC-MS/MS analysis on equivalent amounts of proteins, the protein concentration is measured on the ground material. The results are expressed as an expression ratio between the treated case and the control case. A ratio greater than 1.5 is considered as an increase in protein production (+50% compared to the control). A study of variances and a Student's t test is carried out for judging the significance of the results.

[0095] Study by Immunocytofluorescence Labeling on KHN Culture

[0096] Principle: confluent NHKs (n=3) are cultured as above for 7 days in the presence or absence (control) of the peptide according to the invention then the cell layers are fixed and labels by immunocytochemistry are carried out using antibodies directed against proteins characteristic of the maturation of the epidermis: involucrine, loricrin and filaggrin. Photos are captured using a fluorescence microscope and images analyzed using appropriate software. The results are compared with those of the control. The number of cells on the mats is evaluated by the Hoechst method (DNA staining), to reduce the fluorescence value to the number of cells. A variance study and a Student's t test are carried to judge the significance of the results.

[0097] Propionibacterium acnes Growth Inhibition Test

[0098] Principle: suspensions of Propionibacterium acnes of equivalent density are cultured in a suitable medium in the presence (test case) or absence (control case) of the peptide according to the invention, in anaerobic condition, at 37° C. Samples are taken at regular intervals to measure the OD at 600 nm for following the growth of the bacterial population over time. The growth curve of each culture is thus established.

[0099] 1. Improvement of the Epidermal Barrier and Harmonization of the Maturation of the Epidermis

[0100] The cornified layer or stratum corneum is an assembly of great complexity associating, on the one hand, cells without nucleus, flat and strongly linked to each other and, on the other hand, lipids and proteins whose composition and assembly ensure the unique properties of this structure very resistant to physical, chemical and biological attacks from the environment.

[0101] The test results given below show that the peptide according to the invention improves epidermis homeostasis and skin barrier reinforcement, thanks to the assay of different markers involved in epidermal differentiation and barrier formation.

[0102] The keratinocytes gradually mature by acquiring a very resistant outer shell formed of proteins called involucrine and loricrin, linked together thanks to the intervention of transglutaminases, enzymes sensitive to calcium. In addition, SPRRs (Small Proline Rich Region Proteins), other proteins involved in maturation and homeostasis of the stratum corneum, serve to strengthen this protein shell by creating flexible but resistant bridges between proteins, again thanks to the activity of transglutaminases. There are also the LCEs (“Late Cornified Envelope Proteins”) which are among the last components to be bridged during the maturation phase. Furthermore, ceramides are of great importance in the formation of the stratum corneum and of its proteolipid matrix, hence the importance of cosmetic active ingredients stimulating the synthesis of these elements. A good barrier function is also very dependent on the filaggrins which are produced by the keratinocytes where they undergo significant metabolism. They serve for a time to stabilize the corneocyte by binding to the keratins and then end up being broken down into amino acids giving essential components of the natural hydration factor (NMF) found in the stratum corneum, which allows a good hydration of the skin

[0103] Furthermore, kallikreins are proteases involved in the renewal of the stratum corneum by allowing natural desquamation, thus ensuring a gentle “natural” smoothing effect. The increased expression and synthesis of these enzymes improves the natural process of corneocyte desquamation and may be similar to a natural peel.

[0104] 1.1. Action on Epidermal Differentiation and Stratum Corneum Formation

[0105] 1.1.1. Induction of the formation of involucrin, loricrin and filaggrin in NEM (by immunofluorescence)/effect of 5 ppm of the peptide according to the invention:

TABLE-US-00001 TABLE 1 Involucrin: Loricrin: Filaggrin: % of variation/ % of variation/ % of variation/ Concentrations control control control Control Reference Reference Reference 5 ppm +1057%; p < 0.05 +128%; p < 0.01 +310%; p < 0.01

[0106] 1.1.2. Variation compared to the control of the expression of genes (DNA-Array) coding for proteins of epidermal differentiation and formation of the stratum corneum/effect of 7 ppm of the peptide according to the invention at 24/48 hours of contact:

TABLE-US-00002 TABLE 2 Expressed gene Variation Name and function of the protein PRSS8 ×3.72 Serine protease 8; cleaves profilaggrin into filaggrin. ASPRV1 ×3.35 Skin aspartic protease; cleaves profilaggrin into filaggrin. LOR ×1.86 Loricrin; major protein of the stratum corneum which confers to it cohesion/rigidity; linked to the other proteins of the envelope by the enzymatic action of TGM1 (see below). TGM1 ×1.70 Transglutaminase 1; enzyme that cross-links between different structural proteins, at the level of the homy envelope, to ensure its rigidity. SPRR2A ×8.71 Small Proline Rich Region Proteins; maturation and homeostasis SPRR2C ×6.30 proteins of the stratum corneum, serve to strengthen the protein SPRR2E ×6.47 shell of the corneocyte by creating flexible but resistant bridges SPRR3 ×1.90 between proteins, here again thanks to the activity of SPRR2F ×6.00 transglutaminases SPRR2D ×7.87 SPRR2B ×58.44 SPRR2G ×13.43 SPRR4 ×2.95 LCE3A ×65.26 Late Cornified Envelop Proteins; these are the last components to LCE3B ×123.00 be bridged during the maturation phase in the stratum corneum. LCE3D ×110.46 LCE3E ×135.99 LCE2C ×26.30 CRNN ×4.73 Cornulin; marker of terminal epidermal differentiation. (48 h) TCHH ×4.87 Trichohyalin; structural protein that helps strengthen the barrier (48 h) by cross-bridging with other proteins in the stratum corneum using the enzyme TGM1. BMP6 ×13 Bone morphogenetic protein 6; regulates positively keratinocyte differentiation (including expression of keratin 1) through multiple signaling systems.

[0107] 1.1.3. Variation compared to the control of proteins related to the maturation of the epidermis (by LC-MS/MS)/effect of 5 ppm of the peptide according to the invention:

TABLE-US-00003 TABLE 3 Protein Variation Name and function of the protéine FLG ×2.66; p < 0.01 Filaggrin; as disclosed above LOR ×2.92; p < 0.01 Loricrin; as disclosed above ASPRV1 ×2.35; p < 0.01 Skin aspartic protease; cleaves profilaggrin into filaggrin. CALM5 ×1.61; p < 0.01 Calmodulin 5; forms a complex with calcium; calmodulins control many enzymes, ion channels, aquaporins and other proteins through their binding with calcium. TCHH ×1.54; p < 0.01 Trichohyalin; as disclosed above KRT1 ×1.58; p < 0.01 Keratins; main epidermis constituent, at the stratum corneum KRT9 ×1.54; p < 0.01 level; form an intracellular network; in the form of filaments KRT10 ×1.75; p < 0.01 sheathed by a shell of strongly crosslinked proteins and are KRT15 ×2.02; p < 0.01 connected to the desmosomes.

[0108] 1.1.4. Variation compared to the control of the gene expression of involucrin and transglutaminase 1 to 24 hours (by RT-PCR)/effect of the peptide according to the invention at 5 ppm:

TABLE-US-00004 TABLE 4 Expressed gene Variation Name and function of the protein Involucrine ×1.64; p < 0.01 Involucrin; major protein of the stratum corneum which confers its cohesion/rigidity; linked to other envelope proteins by the enzymatic action of TGM1 (see above) Transglutaminase 1 ×1.82; p < 0.05 As disclosed above

[0109] 1.2. Action on the Formation of Lipidic Lamellar Bodies

[0110] Variation compared to the control of the expression of genes (DNA-Array) encoding proteins involved in the formation of the lipid envelope of the corneocyte/effect of 7 ppm of the peptide according to the invention at 24 or 48 hours of contact:

TABLE-US-00005 TABLE 5 Expressed gene Variation Name and function of the protein ALOX12B ×2.48 Arachidonate 12-lipoxygenase; acts upstream of ALOXE3 on the lineolate fragment of esterified omega-hydroxyacyl- sphingosin ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins; therefore plays a crucial role in the synthesis of the lipid envelope of corneocytes and in the establishment of the skin barrier. ALOXE3 ×2.92 Hydroperoxide isomerase; acts downstream of ALOX12B on the linoleate moiety of esterified omega-hydroxyacyl- sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega- hydroxyceramide to membrane proteins; therefore plays a crucial role in the synthesis of the lipid envelope of corneocytes and in the establishment of the skin barrier. CERS1 ×3.48 Ceramide synthase 1; catalyzes the formation of ceramides (48 h) from sphinganine substrates and acyl-CoA. ELOVL4 ×5.41 3-keto acyl-CoA synthase; catalyzes the limiting step of the 4 reactions of the cycle of elongation of long chain fatty acids; formation of the corneocyte lipid envelope. ABHD5 ×2.10 1-acylglycerol-3-phosphate O-acyltransferase; this enzyme plays a crucial role in lipid metabolism within the lamellar bodies, contributing to the formation of the skin lipid barrier.

[0111] 1.3. Action on the Formation of Desmosomes, Corneodesmosomes and Tight Junctions

[0112] Variation compared to the control of the expression of genes (DNA-Array) encoding proteins involved in the formation of desmosomes, corneodesmosomes and tight junctions/effect of 7 ppm of the peptide according to the invention at 24 hours of contact:

TABLE-US-00006 TABLE 6 Expressed gene Variation Name and function of the protein CDSN ×3.36 Coneodesmosin; presence essential for the integrity of the epidermal barrier; protein specific to corneodesmosomes for promoting their adhesion. OCLN (*) ×5.91 Occludin; plays an important role in the formation and regulation of tight junction; capable to induce adhesion when expressed in cells lacking tight junctions. TJP1 ×2.15 Tight junction protein ZO-1; structural protein connecting tight junction transmembrane proteins such as claudins and occludin to the actin cytoskeleton. CGNL1 ×3.37 Cingulin-like protein 1; involved in the anchoring of tight junctions to the actin cytoskeleton. CLDN4 ×5.16 Claudins; proteins present at the level of the tight junctions CLDN7 ×4.47 which ensure cohesion between the corneocytes, via the actin CLDN12 ×2.68 network in the upper part of the epidermis; they therefore CLDN15 ×4.80 have a guardian role for water homeostasis, preventing the CLDN17 ×113.20 evaporation of water. CLDN23 ×3.69 DEFB103B Very Human Beta defensin 3; improves the barrier function via the strongly tight junctions, by the CCR6 receptor, but also by a strong expressed induction of claudins (see in this tabic), aPKC kinases, Rac1 essential in the regulation of tight junctions, GSK3 involved in the expression of tight junction proteins. (*) effect confirmed by RT-PCR (×3.03 for 5 ppm of PalTTTKS at 24 hours of contact)

[0113] 1.4. Desquamation Regulation

[0114] Variation compared to the control of the expression of genes (DNA-Array) encoding proteins involved in the regulation of desquamation/effect of 7 ppm of the peptide according to the invention at 24 hours of contact:

TABLE-US-00007 TABLE 7 Expressed gene Variation Name and function of the protein KLK14 ×1.79 Kallikrein-14; serine protease which cleaves desmoglein during epidermal desquamation (corneocytcs excreted from the surface of the skin).

[0115] Conclusion: It appears that the peptide according to the invention acts at all the levels studied: from the metabolization of filaggrin to the regulation of desquamation, including the production of elements of the stratum corneum, the formation of lipid lamellar bodies, the formation of tight junctions in a way that improves and strengthens the epidermal barrier.

[0116] The peptide according to the invention thus acts favorably to guarantee the homeostasis of the epidermis, ensuring a good balance between the renewal by differentiation of the cells and the formation of a skin barrier of effective quality in particular with regard to external attacks. This type of activity profile guarantees good re-epithelialization of the skin tissue in subjects who have experienced an acne episode, by reducing unaesthetic acne scars.

[0117] 2. Skin Protection Action Including Defense Against Bacteria, Inflammation, Radiation and Immunity Stimulation

[0118] 2.1. Human Beta Defensin 3 (HBD3) and Other Markers

[0119] HBD3 is an antimicrobial peptide that intervenes at several levels. It is a key molecule in the skin's immune system. In particular, it has a broad spectrum of destruction against bacteria and yeasts. Thus, stimulating the expression of this peptide has a great interest in cosmetics, on the one hand in the prevention and treatment of acne (against the Propionibacterium acnes bacterium) and on the other hand to treat a dandruff condition (against yeasts of the genus Malassezia). Recently, it was found that these antimicrobial defense peptides have a broader action in the skin and that they have a role in cell proliferation, migration and differentiation, in the regulation of inflammatory responses, by controlling the production of different cytokines, in the development of cicatrisation in the epidermis, and in improving the barrier function.

[0120] The peptide according to the invention has an anti-inflammatory role demonstrated by the DNA-Array with the induction of the anti-inflammatory cytokine IL-37. It is further described as involved in skin immunity via the production of various cytokines/chemokins. Furthermore, it is also described to counter the inflammatory effects of bacterial lipopolysaccharide. Finally, it has feedback control of inflammatory activity by inhibiting the TLR (Toll Like receptor) pathway.

[0121] Thus, the peptide according to the invention, comprised a cosmetic composition, by being capable of strongly stimulating the gene expression of human beta defensin 3, an integral part of the innate immune system, will have a defensive action to prevent penetration or proliferation of infectious agents in the skin. It is an immediate response, in the form of inflammatory reactions, not specific to the pathogen agent.

[0122] The peptide according to the invention also stimulates the expression of the SOD2 gene, important in the defense of the skin against free radicals (here the superoxide radical).

[0123] A direct action against the bacteria Propionibacterium acnes enhances the interest of the peptide according to the invention for fighting acne.

[0124] Results

[0125] Variation compared to the control of the expression of genes (DNA-Array) encoding proteins involved in the protection of the skin/effect of 7 ppm of the peptide according to the invention at 24 or 48 hours of contact:

TABLE-US-00008 TABLE 8 Expressed gene Variation Name and function of the protein DEFB103B Very strongly Human Beta Defensin 3; as disclosed expressed above SOD2 ×2.93 Superoxide dismutase 2; destroys the (48 hours) superoxide anion radicals normally produced in cells and which are toxic to biological systems. IL37 ×3.60 Interleukin-37; suppresses or reduces the production of pro-inflammatory cytokins, including IL1a and IL6.

[0126] Variation compared to the control of proteins involved in the protection of the skin (by LC-MS/MS)/effect of 5 ppm of the peptide according to the invention:

TABLE-US-00009 TABLE 9 Expressed gene Variation Name and function of the protein SPINK5 ×1.58; p < 0.01 Serine protease inhibitor Kazal-type 5; serine protease inhibitor, important for anti-inflammatory and/or antimicrobial protection of the skin; contributes to the integrity and barrier function of the skin by regulating the activity of proteases involved in the desquamation and defense of the skin.

[0127] 2.2. Specific Action Against Propionibacterium acnes

[0128] Growth of the bacterium Propionibacterium acnes: time necessary to reach an OD of 1 in the control case and in the presence of the peptide according to the invention (N=2 independent experiments; n=2 cultures per case):

TABLE-US-00010 TABLE 10 6 ppm of 9 ppm of 12 ppm of Cases Control peptide peptide peptide Time in hours 28 42 54 85.5

[0129] These data show that the peptide according to the invention strongly and dose-dependently inhibits the growth of Propionibacterium acnes.

[0130] 2.3. Alpha Crystallin

[0131] Alpha-crystallin is a small protein related to the HSP family (or heat shock proteins). It is present in the epidermis, where it protects epithelial cells, restores their mitochondrial functions, and increases their resistance to oxidative stress. This protein has the property of being found in the cell and in its immediate vicinity. Therefore, the skin is protected from UV, inflammatory and more generally oxidative attacks by its presence.

[0132] Variation compared to the control of the expression of the alpha-crystallin B gene 1 to 24 hours (by RT-PCR)/effect of the peptide according to the invention at 5 ppm:

TABLE-US-00011 TABLE 11 Expressed gene Variation Name and function of the protein CRYAB ×3.47; p < 0.01 Alpha-crystallin B; as disclosed above

[0133] Variation compared to the control of proteins involved in the defense of the skin (by LC-MS/MS)/effect of 5 ppm of the peptide according to the invention:

TABLE-US-00012 TABLE 12 Expressed gene Variation Name and function of the protein CRYAB ×2.24; p < 0.01 Alpha-crystallin B; as disclosed above

[0134] 2.4. Moderation of the Production of Inflammation Markers

[0135] The skin is subjected to constant stress (exposure to UV rays, smoke, pollutants, etc.) some of which provoke a direct or indirect inflammatory response. The uncontrolled or constant inflammatory response, although of low intensity, leads to the production of cytokines such as IL-1α, IL-1β, IL-6, TNF α, and lipids such as PGE2 intended to attract or stimulate other cells, causing cascading reactions. The pro-inflammatory microenvironment thus formed leads to modify the homeostasis of the skin and gradually leads to the modification or even destruction of the biomolecules of cells and tissues. It also leads to the disruption of the skin barrier integrity. Thus, the mediators of inflammation, IL-6 and PGE-2, are known to induce, via micro-inflammations, the phenomena of premature aging. In addition, sensitive and irritated skin is characterized by an abnormally high secretion of cytokines, pro-inflammatory peptides (IL-1, IL-6 for example) and pro-inflammatory lipids (PGE-2 for example).

[0136] To test the active ingredients, keratinocytes were placed in culture under light stress conditions (application of UVB radiation) to mimic an experimental skin micro-inflammation. In this situation, a significant decrease in their secretome of inflammation mediators will be interpreted in the sense of a restorative and protective action of the skin.

[0137] Results:

[0138] Variation compared to the control of the secretome of pro-inflammatory mediators by NHKs exposed to UVB (by immunoenzymatic assay)/effect of the peptide according to the invention at 4, 6 and 8 ppm:

TABLE-US-00013 TABLE 13 Marker 4 ppm 6 ppm 8 ppm IL6 −13% (ns) −68% (p < 0.01) −84% (p < 0.01) PGE2 −41% (p < 0.01) −69% (p < 0.01) −84% (p < 0.01) ns: non-significant

[0139] These results show the very interesting effect of the peptide according to the invention for moderating the secretion of pro-inflammatory mediators by NHKs which have been exposed to UVB irradiation. This effect is particularly interesting for sensitive skin irritated by exposure to radiations and various pollutants that cause micro-inflammations.

[0140] To these results is also added the expression of the IL37 gene mentioned above.

[0141] Conclusion:

[0142] The peptide according to the invention regulates in the sense of an enhanced defense of the skin against bacteria, oxidants, radiation and against the resulting inflammation, all the markers studied acting toward this aim.

[0143] 3. Action to Prevent and Treat Scars on the Epidermis

[0144] Human Beta Defensin 3 participates in cicatrisation by promoting keratinocyte migration and proliferation. These actions imply phosphorylation induction of EGFR, a signal transducer and of STAT1 and STAT3, intracellular signaling molecules known to be involved in keratinocyte migration and proliferation.

[0145] Certain tight junction (TJ) proteins, such as occludin, are also involved in keratinocyte migration and proliferation. These processes are essential for the healing of normal skin wounds and the regeneration of the epidermis.

[0146] The signaling pathways of BMPs, members of the TGFβ superfamily, regulate the healing process by directing keratinocytes either in the proliferative pathway or towards differentiation, depending on the stage of healing.

[0147] Variation compared to the control of the expression of genes (DNA-Array) coding for proteins involved in cicatrising/effect of 7 ppm of the peptide according to the invention at 24 or 48 hours of contact:

TABLE-US-00014 TABLE 14 Expressed gene Variation Function of the protein DEFB103B Very strongly Human Beta defensine 3; as disclosed above expressed ADGRG1 ×1.92 Receptor 56 coupled to G protein; involved in cell adhesion and probably in cell-cell interactions. FN1 ×3.38 Fibronectin 1; fibronectins bind to the surface of cells. They are involved in cell adhesion, cell motility, wound healing, and the maintenance of cell shape. GSK3B ×1.64 Glycogène synthase kinase 3 beta; GSK-3beta controls the progression of wound healing by modulating endothelin-1 levels. BMP2 ×3.63 Bone morphogenetic protein 2; as disclosed above BMP6 ×13 Bone morphogenetic protein 6; as diclosed above OCLN (*) ×5.91 Occludin; as disclosed above PPARD ×1.97 Peroxisome proliferator activated receptor delta; transcription factor involved in epidermal differentiation, maintenance of epidennal homeostasis and anti-inflammatory response. (*) effect confirmed by RT-PCR (×3.03 for 5 ppm of PalKTTKS at 24 hours of contact)

[0148] Variation compared to the control of proteins involved in healing (assay by LC-MS MS)/effect of 5 ppm of the peptide according to the invention:

TABLE-US-00015 TABLE 15 Protein Variation Name and function of the protein THBS1 ×1.98; Thrombospondin-1; An adhesive glycoprotein p < 0.01 that is involved in cell-to-cell and cell-to- matrix interactions. ADGRG1 ×1.63; Receptor 56 coupled to G protein; as disclosed p < 0.01 above KRT6 ×1.47; Keratin 6; induced during healing, at the p < 0.01 suprabasal level.

[0149] Conclusion:

[0150] All the studied markers show that the peptide according to the invention acts in the keratinocyte level by improving the healing process.

[0151] 4. Beneficial Action on Nails and Hair

[0152] 4.1. On Nails

[0153] The BMPs, members of the TGFβ superfamily, are involved in nail differentiation and development. They promote communication between the epidermis and the mesenchyme, and coordinate differentiation, by activating transcription factors.

[0154] Variation compared to the control of the expression of genes (DNA-Array) encoding constituent proteins of the nail or involved in its formation/effect of 7 ppm of the peptide according to the invention at 24 or 48 hours of contact:

TABLE-US-00016 TABLE 16 Gene Variation Name and function of the protein TCHH ×4.87 Trichohyalin; present in the nail bed (48 hours) BMP2 ×3.63 Bone morphogenetic protein 2; as disclosed above BMP6 ×13 Bone morphogenetic protein 6; as disclosed above

[0155] Variation compared to the control of constituent proteins of the nail or involved in its formation (assay by LC-MS/MS). Effect of 5 ppm of the peptide according to the invention.

TABLE-US-00017 TABLE 17 Protein Variation Name and function of the protein KRT6 ×1.47; p < 0.01 Keratinc 6; present in the nail bed TCHH ×1.54; p < 0.01 Trichohyaline; present in the nail bed KRT 1 ×1.58; p < 0.01 Keratine 1; present in the suprabasal matrix, absent from the bed KRT 10 ×1.75; p < 0.01 Keratine 10; present in the suprabasal matrix, absent from the bed FLG ×2.66; p < 0.01 Filaggrine; present in the nail bed

[0156] Conclusion:

[0157] Several compounds of the nail itself and of compounds involved in its formation have their gene expression and/or their concentration increased following contact with the peptide according to the invention. This was observed in the DNA-Array and in the LC-MS/MS protein study.

[0158] The compound according to the invention thus appears to be perfectly indicated for the maintenance of healthy nails or the treatment of damaged nails.

[0159] 4.2. On Hair

[0160] Morphogenesis of hair follicles and initiation of a growth phase of quiescent hair follicles, are characterized by the activation of different signaling pathways resulting in the construction of a hair shaft. Among the different signaling pathways, the balance between the activities of the Wnt/β-catenin and BMP pathways is particularly important.

[0161] BMPs therefore participate in the regulation of hair growth by inhibiting the proliferation phase of dermal papilla cells and stimulating the differentiation of cells synthesizing the hair shaft. Conversely, the Wnt/β-catenin pathway results in the activation of proliferation of the dermal papilla cells.

[0162] Trichohyalin is expressed in specific epithelia, exceptionally strong mechanically, such as the cells in the inner sheath of the hair follicle. It is subjected to modifications by enzymes, in particular transglutaminases, which introduce intra- and inter-proteic cross-links. It is a multifunctional protein cross-linked by bridges that functions inside the hair's inner root sheath, imparting and coordinating mechanical strength between peripheral cell envelope structures and the cytoplasmic keratin filament network.

[0163] Variation compared to the control of the expression of genes (DNA-Array) encoding constituent proteins of the hair or involved in its formation/effect of 7 ppm of the peptide according to the invention at 24 or 48 hours of contact:

TABLE-US-00018 TABLE 18 Expressed gene Variation Function of the protein TCHH ×4.87 Trichohyalin; as disclosed above (48 hours) BMP2 ×3.63 Bone morphogenetic protein 2; as disclosed above BMP6 ×13 Bone morphogenetic protein 6; as disclosed above GSKA ×1.57 Glycogene synthase kinase 3 alpha; regulates hair growth GSKB ×1.64 Glycogene synthase kinase 3 beta; key enzyme in the Wnt/β-catenin signaling pathway that regulates hair growth.

[0164] Variation compared to the control of proteins constituting the hair or involved in its formation (assay by LC-MS/MS)/effect of 5 ppm of the peptide according to the invention:

TABLE-US-00019 TABLE 19 Expressed gene Variation Function of the protein KRT6 ×1.47; p < 0.01 Keratin 6; expressed in the outer sheath of the hair follicle. KRT6B ×2.07; p < 0.01 Keratin 6B; constitutively expressed TCHH ×1.54; p < 0.01 Trichohyalin; as disclosed above

[0165] Conclusion:

[0166] A certain number of compounds of the hair itself and of compounds involved in its formation have their gene expression and/or their concentration increased following contact with the peptide according to the invention. This was observed in the DNA-Array and in the LC-MS/MS protein study.

[0167] The compound according to the invention thus appears to be perfectly indicated for an action in the hair field to improve the strength and growth of the hair.

D) Galenics/Preparation of a Composition According to the Invention

[0168] The peptide according to the invention can be formulated with additional cosmetic active ingredients, that can come in support and/or in complement of activity, either in the ingredient form, or at the time of the realization of the final cosmetic composition for the consumer. This composition can be applied to the face, body, neckline, scalp, hair, eyelashes, body hair, in any form or vehicles known to those skilled in the art, in particular in the form of solution, dispersion, emulsion, paste or powder, individually or as a premix or be conveyed individually or as a premix.

[0169] In cosmetics, applications can be proposed in particular in the ranges of skin care for the face, body, hair and body hair and ranges of make-up treatments.

[0170] These ingredients can be of any category depending on their function(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, tensor, moisturizer, nourishing, protective, smoothing, remodeling, volumizing (lipofiling), acting on the radiance of the complexion, anti-dark spots, concealer, anti-glycation, anti-aging, anti-wrinkle, slimming, soothing, myo-relaxing, anti-redness, anti-stretch marks, sunscreen, etc.

[0171] The CTFA (“International Cosmetic Ingredient Dictionary & Handbook” (19th Edition, 2019) published by “The Cosmetic, Toiletry, and Fragrance Association, Inc.”, Washington, D.C.) describes a wide variety, without limitation, of cosmetic ingredients usually used in the skincare industry, which are suitable for use as additional ingredients in the compositions of the present invention.

[0172] At least one of the compounds can be cited selected from vitamin B3 compounds, compounds such as niacinamide or tocopherol, retinoid compounds such as retinol, hexamidine, α-lipoic acid, resveratrol or DHEA, hyaluronic acid, peptides, in particular N-aceyl-Tyr-Arg-O-hexadecyl ester, Pal-VGVAPG (SEQ ID NO 3), Pal-KTFK (SEQ ID NO 6), Pal-GHK, Pal-KMO.sub.2K, Pal-GQPR (SEQ ID NO 2), Pal-K(P)HG (with a proline grafted on the lysine), and Pal-KTSKS (SEQ ID NO 7), which are known active ingredients used in topical cosmetic or dermo-pharmaceutical compositions.

[0173] Other additional skin care actives that are particularly useful can be found in Sederma's commercial literature and at www.sederma.com or www.crodarom.com.

[0174] For reinforcing the activity on the properties of the epidermis and/or stratum corneum, the additional active agent can be chosen from the group comprising: phospholipids, various ceramides, sphingosine, phytosphingosine, glycosphingolipids, cholesterol and its derivatives, sterols (in particular those of canola and soybean), fatty acids (in particular linoleic acid, palmitic acid, lipoic acid, thioctic acid), squalane (in particular olives), triglycerides (especially coconut oil), lanolin, lanolin alcohols, lanosterol, vitamin D3, tocopheryl nicotinate, various oils (in particular, argan, rose, baobab), ascorbic acid, N-acetyl cysteine and N-acetyl-L-serine, vitamin B3 compounds (such as niacinamide and nicotinic acid), panthenol, pseudofilaggrin, arginine, serine, salts of PCA (pyrrolidone carboxylic acid) an extract of Centella asiatica leaf (titrated in madecasso side and asiaticoside), certain plant extracts (wild yam roots, chestnut, cedar bud, nightshade), plankton and yeast.

[0175] Mention may also be made of the active agents marketed by Sederma: Venuceane™ (extract of fermentation medium of Thermus thermophilus), Moist24™ (hydroglycolic extract of Imperata cylindrica root), Dermaxyl™ (combination of ceramide 2 and the Pal-VGVAPG peptide), Senestem™ (a cell culture extract of Plantago lanceolata), Ceramide 2™ (ceramide), Ceramide HO3™ (hydroxyceramide), Optim Hyal™ (acetylated glucuronic acid oligosaccharides), Meiritage™ (combination of root extracts of Bupleurum falcatum, Astragalus membranaceus, Atractylodes macrocephala), Revidrat™ (myristyl phosphomalate), Pacifeel™ (an extract of Mirabilis jalapa), Hydronesis™ (resulting from the fermentation of Salinococcus hispanicus), NG unsaponifiable Shea™ and Citystem™ (a cell culture extract of Marrubium vulgare). The following commercial actives can also be mentioned as examples: betain, glycerol, Actimoist Bio 2™ (Active organics), AquaCacteen™ (Mibelle AG Cosmetics), Aquaphyline™ (Silab), AquaregulK™ (Solabia), Carciline™ (Greentech), Codiavelane™ (Biotech Marine), Dermaflux™ (Arch Chemicals, Inc), Hydra′Flow™ (Sochibo), Hydromoist L™ (Symrise), RenovHyal™ (Soliance), Seamoss™ (Biotech Marine), Argireline™ (commercial name of acetyl hexapeptide-3 from Lipotec), spilanthol or an extract of Acmella oleracea known under the trade name Gatuline Expression™, an extract of Boswellia serrata known under the name Boswellin™, Deepaline PVB™ (Seppic), Syn-AKE™ (Pentapharm), Ameliox™, Bioxilift™ (Silab), PhytoCellTec™ Argan (Mibelle), Papilactyl D™ (Silab), Preventhelia™ (Lipotec), or one or more of the following active ingredient sold by Sederma: Subliskin™, Venuceane™, Moist24™, Vegesome Moist24™, Essenskin™, Juvinity™ Revidrat™, Resistem™, Chronodyn™, Kombuchka™, Chromocare™, Calmosensine™, Glycokin factor S™, Biobustyl™, Idealift™, Ceramide 2™, Ceramide A2™, Ceramide HO3™, Legance™ Intenslim™, Prodizia™, Beautifeye™, Pacifeel™, Zingerslim™, Meiritage™, Senestem™, Sebuless™, Majestem™, Apiscalp™, Rubistem™, Citystem™, Neonyca™, NG Insaponifiables de Beurre de Karité™, Majestem™, Hydronesis™, Poretect™, Crystalide™, Amberstem™, Synchrolife™, Feminage™, or mixture thereof.

[0176] Among plant extracts (in the form of classical plant extracts or prepared by an in vitro process) that can be combined with plant cells of Buddleja davidii Franch. according to the present invention, there may more particularly be mentioned extracts of Ivy, in particular English Ivy (Hedera helix), of Bupleurum chinensis, of Bupleurum falcatum, of arnica (Arnica montana L), of rosemary (Rosmarinus officinalis N), of marigold (Calendula officinalis), of sage (Salvia officinalis L), of ginseng (Panax ginseng), of Gingko biloba, of St.-John's-Wort (Hyperycum perforatum), of butcher's-broom (Ruscus aculeatus L), of European meadowsweet (Filipendula ulmaria L), of big-flowered Jarva tea (Orthosiphon stamincus benth), of artichoke (Cynara scolymus), of algae (Fucus vesiculosus), of birch (Betula alba), of green tea, of cola nuts (Cola nipida), of horse-chestnut, of bamboo, of Centella asiatica, of heather, of fucus, of willow, of mouse-ear, of escine, of cangzhu, of Chrysanthellum indicum, of the plants of the Armeniacea genus, Atractylodis platicodon, Sinnomenum, Pharbitidis, Flemingia, of Coleus such as C. Forskohlii, C. blumei, C. esquirolii, C. scutellaroides, C. xanthantus and C. Barbatus, such as the extract of root of Coleus barbatus, extracts of Ballote, of Guioa, of Davallia, of Terminalia, of Barringtonia, of Trema, of Antirobia, Cecropia, Argania, Dioscoreae such as Dioscorea opposita or Mexican, extracts of Ammi visnaga, of Siegesbeckia, in particular Siegesbeckia orientalis, vegetable extracts of the family of Ericaceae, in particular bilberry extracts (Vaccinium angustifollium) or Arctostaphylos uva ursi, aloe vera, plant containing sterols (e.g., phytosterol), Manjistha (extracted from plants of the genus Rubia, particularly Rubia cordifolia), and Guggal (extracted from plants of the genus Commiphora, particularly Commiphora mukul), kola extract, chamomile, red clover extract, Piper methysticum extract (Kava Kava™ from Sederma), Bacopa monieri extract (Bacocalmine™ from Sederma) and sea whip extract, extracts of Glycyrrhiza glabra, of mulberry, of melaleuca (tea tree), of Larrea divaricata, of Rabdosia rubescens, of Euglena gracilis, of Fibraurea recisa Hirudinea, of Chaparral Sorghum, of sun flower extract, of Enantia chlorantha, of Mitracarpe of Spermacocea genus, of Buchu barosma, of Lawsonia inermis L., of Adiantium capillus-veneris L., of Chelidonium majus, of Luffa cylindrica, of Japanese Mandarin (Citrus reticulata Blanco var. unshiu), of Camelia sinensis, of Imperata cylindrica, of Glaucium flavum, of Cupressus sempervirens, of Polygonatum multiflorum, of Loveyly hemsleya, of Sambucus nigra, of Phaseolus lunatus, of Centaurium, of Macrocystis pyrifera, of Turnera diffusa, of Anemarrhena asphodeloides, of Portulaca pilosa, of Humulus lupulus, of Coffea arabica, of Ilex paraguariensis, or of Globularia cordifolia, of Albizzia julibrissin, of Oxydendron arboretum, of Zingimber zerumbet smith, of Astragalus membranaceus, of Atractylodes macrocephala, of Plantago lanceolata, of Leontopodium alpinum, of Mirabilis jalapa, of Apium graveolens, of Marrubium vulgare, Buddleja davidii Franch, Engelhardia chrysolepis, Syringa vulgaris or orchids.

[0177] The compositions of the present invention may include one or more additional peptides, including, without limitation, di-, tri-, tetra-, penta- and hexapeptides and their derivatives. According to a particular embodiment, the concentration of the additional peptide, in the composition, ranges from 1×10.sup.−7% and 20%, preferably from 1×10.sup.−6% and 10%, preferably between 1×10.sup.−5% and 5% by weight. The term “peptide” refers here to peptides containing 10 amino acids or less, their derivatives, isomers and complexes with other species such as a metal ion (e.g. copper, zinc, manganese, magnesium, and others). The term “peptides” refers to both natural peptides and synthetic peptides. It also refers to compositions that contain peptides and which are found in nature, and/or are commercially available.

[0178] Suitable dipeptides for use herein include but are not limited to Carnosine (βAH), YR, VW, NF, DF, KT, KC, CK, KP, KK, TT, PA, PM or PP.

[0179] Suitable tripeptides for use herein include, but are not limited to RKR, HGG, GKH, GHK, GGH, GHG, KGH, KHG, KFK, KAvaK, KβAK, KAbuK, KAcaK, KPK, KMOK, KMO.sub.2K (MO.sub.2 being a di-oxygenated sulfoxide methionine), KVK, PPL, PPR, SPR, QPA, LPA, SPA, K(Ac)HG or K(Ac)GH, K(Ac) being a lysine with the amine function of the lateral chain acetylated, as disclosed in WO2017/216177, K(P)HG or K(P)GH, K(P) being a lysine with its lateral chain grafted with a proline, K(Pyr)HG or K(Pyr)GH, K(Pyr) being a lysine with its lateral chain grafted with a pyroglutamic acid, K(Hyp)HG or K(Hyp)GH, K(Hyp) being a lysine with its lateral chain grafted with a hydroxyproline, as disclosed in WO2016/097965.

[0180] Suitable tetrapeptides for use as additional peptides herein include but are not limited to RSRK (SEQ ID NO: 8), GQPR (SEQ ID NO: 9), KTFK (SEQ ID NO: 10), KTAK (SEQ ID NO: 11), KAYK (SEQ ID NO: 12) or KFYK (SEQ ID NO: 13).

[0181] A suitable non limitative example of pentapeptide is the KTSKS (SEQ ID NO: 14), and suitable examples of hexapeptides are the GKTTKS (SEQ ID NO: 15), GKTSKS (SEQ ID NO: 16) and VGVAPG (SEQ ID NO: 17).

[0182] Other suitable peptides for use according to the present invention can be selected, this list being not limitative, from: lipophilic derivatives of peptides, preferably palmitoyl (Pal) derivatives or myristoyl (Myr), and metal complexes as aforementioned (e.g. copper complex of the tripeptide HGG or GHK). Preferred dipeptides include for example N-Palmitoyl-β-Ala-His, N-Acetyl-Tyr-Arg-hexadecylester (Calmosensine™, Idealift™ from Sederma), Pal-RT or Pal-KT (from Sederma).

[0183] Preferred tripeptide derivatives include for example Pal-GKH and Pal-GHK (from Sederma), the copper derivative of HGG (Lamin™ from Sigma), Lipospondin (N-Elaidoyl-KFK) and its analogs of conservative substitution, N-Acetyl-RKR-NH.sub.2 (Peptide CK+), N-Biot-GHK (from Sederma), Pal-KAvaK, Pal-KβAlaK, Pal-KAbuK, Pal-KAcaK, or Pal-KMO.sub.2K (Matrixyl® synthe'6® from Sederma), Pal-KVK (Syn-Coll™ of DSM), and derivatives thereof.

[0184] Mention may also be made here of the anti-aging tripeptides of general Formula X-Pro*-Pro*-Xaa-Y described in WO2015181688 application with Xaa selected from Leu, Arg, Lys, Ala, Ser, and Asp, at the N-terminus, X chosen from H, —CO—R.sup.1 and —SO.sub.2—R.sup.1 and at the C-terminal end Y chosen from OH, OR.sup.1, NH.sub.2, NHR.sup.1 or NR.sup.1R.sup.2, R.sup.1 and R.sup.2 being, independently of one another, chosen from a alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfurized, said group possibly possessing in its backbone a heteroatom particularly O, S and/or or N, and Pro* corresponding to Proline, an analogue or derivative thereof; comprising, for example, Myr-PPL-OH and Myr-PPR-OH.

[0185] Here can further be cited also the propigmenting and/or pro-mec dipeptides and tripeptides of general Formula X-(Xaa.sub.1).sub.n-Pro*-Xaa.sub.2-Y disclosed in WO2014/080376, with n=0, 1 or 2, Xaa.sub.1 an hydrophobic aminoacid selected from Ala, Val, Met, Leu, Iso, Phe, Pro, and analogs and derivatives thereof; or a polar aminoacid selected from Ser, Thr, Tyr, Asp, Glu and analogs and derivatives thereof; and when n=2 the two aminoacids Xaa.sub.1 being the same or different; Xaa.sub.2 being an hydrophobic aminoacid selected from Ala, Val, Met, Leu, Iso, Phe, and analogs and derivatives thereof, or a basic aminoacid selected from Arg, Lys, His, and analogs and derivatives thereof; at the N terminal end X being selected from H, —CO—R.sub.1 and —SO.sub.2—R.sub.1; at the C terminal end Y being selected from OH, OR.sub.1, NH.sub.2, NHR.sub.1 or NR.sub.1R.sub.2; R.sub.1 and R.sub.2 being, independently from each other, selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy et aryloxy group, that can be linear, branched, cyclic polycyclic, saturated, unsaturated, hydroxylated, carbonylated, phosphorylated and/or sulfured, said group having or not an O, S and/or N heteroatom in its skeleton and Pro* corresponding to a Proline, analog or derivative thereof; comprising for example the following peptides Pal-SPR-OH, Pal-PPR-OH, Pal-QPA-OH, Pal-LPAOH, Myr-SPA-OH, Pal-PM-OH, Pal-PA-OH and Pal-PP-OH.

[0186] Suitable tetrapeptide derivatives for use as additional peptides according to the present invention include, but are not limited to, Pal-GQPR (SEQ ID NO: 2) (from Sederma), Pal-KTFK (SEQ ID NO: 6) or Ela-KTFK (SEQ ID NO: 18), Ela-KTAK (SEQ ID NO: 19), Ela-KAYK (SEQ ID NO: 20) or Ela-KFYK (SEQ ID NO: 21). Suitable pentapeptide derivatives for use as additional peptides herein include, but are not limited to Pal-KTSKS (SEQ ID NO: 7), Pal-YGGFXaa (SEQ ID NO: 22) with Xaa being Leu or Pro, or mixtures thereof.

[0187] Suitable hexapeptide derivatives for use herein include, but are not limited to, Pal-VGVAPG (SEQ ID NO: 3), Pal-GKTTKS (SEQ ID NO: 6), Pal-GKTSKS (SEQ ID NO: 23), Pal-HLDIIXaa with Xaa being Trp, Phe, Tyr, Tic, 7-hydroxy-Tic ou Tpi (SEQ ID NO: 24) and derivatives thereof. The mixture of Pal-GHK and Pal-GQPR (SEQ ID NO: 2) (Matrixyl® 3000, Sederma) can also be mentioned.

[0188] The preferred compositions commercially available containing a tripeptide or a derivative include Biopeptide-CL™, Maxilip™, Biobustyl™, Procapil™ and Matrixyl® synthe'6® of Sederma. The compositions commercially available preferred sources of tetrapeptides include Rigin™, Eyeliss™ Matrixyl® Reloaded and Matrixyl 3000® which contain between 50 and 500 ppm of Pal-GQPR (SEQ ID NO: 2), Crystalide™ and an excipient, proposed by Sederma.

[0189] The following marketed peptides can be mentioned as well as additional active ingredients: [0190] Vialox™ (INCI name=Pentapeptide-3 (synthetic peptide comprising alanine, arginine, isoleucine, glycine and proline)), Syn-ake™ (β-Ala-Pro-Dab-NH-Bzl) or Syn-Coll™ (Pal-Lys-Val-Lys-OH) sold by Pentapharm; [0191] Argireline™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH.sub.2 (INCI name=Acetyl hexapeptide-3) (SEQ ID NO: 25), Leuphasyl™ (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID NO: 26), Aldenine™ (Gly-His-Lys), Trylagen™ (INCI name=Pseudoalteromonas Ferment Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline (reaction product of Citrulline and Tripeptide-10 (synthetic peptide constituted of aspartic acid, isoleucine and lysine)), Tripeptide-1), Eyeseryl™ (Ac-β-Ala-His-Ser-His)(SEQ ID NO: 27), Serilesine™ (Ser-Ile-Lys-Val-Ala-Val) (SEQ ID NO 28) or Decorinyl™ (INCI name: Tripeptide-10 Citrulline=reaction product of Citrulline and Tripeptide-10 (synthetic peptide constituted of aspartic acid, isoleucine and lysine) sold by Lipotec; [0192] Collaxyl™ (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID NO 29)) or Quintescine™ (Cys-Gly) sold by Vincience; [0193] Cytokinol™ LS (casein hydrolysate) sold by Les Laboratoires Serobiologiques/Cognis; [0194] Kollaren™ (Gly-His-Lys), IP2000™ (Pal-Val-Tyr-Val) or Meliprene™ (INCI name=Monofluoroheptapeptide-1: reaction product of acetic acid and a synthetic peptide comprising arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan) sold by l'lnstitut Européen de Biologie Cellulaire; [0195] Neutrazen™ (Pal-His-D-Phe-Arg-NH.sub.2) sold by Innovations; or [0196] BONT-L-Peptide™ (INCI name=Palmitoyl Hexapeptide-19: reaction product of palmitic acid and Hexapeptide-19 (synthetic peptide constituted of asparagine, aspartic acid, lysine and methionine), Timp-Peptide™ (INCI name=Acetyl Hexapeptide-20: reaction product obtained by acetylation of Hexapeptide-20 (synthetic peptide constituted of alanine, glycine, lysine, valine and proline) or ECM Moduline™ (INCI name=Palmitoyl Tripeptide-28: reaction product of palmitic acid and Tripeptide-28 (synthetic peptide constituted of arginine, lysine and phenylalanine) sold by lnfinitec Activos.

[0197] It is also possible to envisage combining the plant cells according to the invention with one or more cyclic peptides, in particular those extracted from linseed oil described in the Applicant's patent application FR1850845.

[0198] Different compositions/formulations according to the invention are described below with some examples of additional active ingredients.

[0199] The active ingredient according to the invention is as described in point C/ above comprising 100 ppm of peptide(s) according to the invention.

[0200] This ingredient is generally formulated within a range of 1 to 5%, preferably 3%. [0201] 1) Cream Form, for Example an Anti-Aging Day Cream for the Face

TABLE-US-00020 TABLE 20 Raw materials INCI name Function % Part A: H.sub.2O / / qsp100 Carbopol ™ Ultrez 10 Carbomer Thickener/ 0.30 gelling agent Part B: Brij S2-SS-(RB) ™ Steareth-2 Emulsifier 0.40 Brij S10-SO-(RB) ™ Steareth-10 Emulsifier 1.20 Crodafos Cetearyl Alcohol (and) Emulsifier/ 4.00 CES-PA-(RB) ™ Dicetyl Phosphate (and) conditionner Ceteth-10 Phosphate Crodacol Cetearyl Alcohol Emollient 150 CS90-PA-(RB) Laurocapram Laurocapram Emollient 2.50 Crodamol ™ C12-15 Alkyl Benzoate Emollient 1.50 AB-LQ-(RB) Crodamol ™ Diethylhexyl Succinate Emollient 7.00 OSU-LQ-(JP) Part C: Glycerin Glycerin Humectant 2.50 Octanediol Caprylyl Glycol Humectant/ 0.50 Emollient 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 according / Active 3.00 to the invention

Example(s) of Additional Ingredient(s)

[0202] 1. a moisturizing/smoothing ingredient such as: [0203] OPTIM HYAL™, marketed by Sederma, contains oligosaccharides of acetylated glucuronic acids having a structure analogous to fragments of hyaluronic acid. [0204] 2. a sebum-regulating ingredient such as: [0205] SEBULESS™, marketed by Sederma, comprising an extract of Syringa vulgaris obtained by in vitro cell culture, purifying sebum regulator, mattifies and refreshes the complexion, blurs imperfections. [0206] PORETECT™, marketed by Sederma, comprising a combination of linseed and celery extracts titrated in cylolinopeptides and senkyunolides, which brings firmness, tone and density to the skin, thus strengthening the pore-supporting structures sagging with age. [0207] 3. In activity reinforcement: an ingredient acting on the elastic properties of the skin/skin barrier such as: [0208] IDEALIFT™, marketed by Sederma, comprising the lipodipeptide N-acetyl-Tyrosyl-Arginyl-O-hexadecyl ester, combating facial flaccidity and improving resistance to gravity, in particular via the stimulation of elastin. [0209] DERMAXYL™, marketed by Sederma, combining ceramide 2, cement of the stratum corneum, and a palmitoylated matrikine Pal-Val-Gly-Val-Ala-Pro-Gly, which smoothes wrinkles and repairs the skin barrier.

[0210] 2) Mild Aqueous Serum Form

TABLE-US-00021 TABLE 21 Raw materials INCI name Function % Part A: H.sub.2O / / qsp100 Potassium sorbate Potassium Sorbate Preservative 0.10 Part B: Glycerin Glycerin Humectant 5.00 Phenoxyethanol Phenoxyethanol Preservative 0.80 Part C: Cromollient ™ Di-PPG-2 Myreth-10 Emollient 1.20 SCE Adipate VisiaOptima ™ Sodium Polyacrylate (and) Rheology 1.00 SE Ethylhexyl Cocoate (and) modifier PPG-3 Benzyl Ether and emulsion Myrisate (and) stabilizer Polysorbate 20 Part D: H.sub.2O / / 0.80 NaOH 30% Sodium Hydroxide pH adjuster 0.08 Part C: Ingredient according / Active 3.00 to the invention

Example(s) of Additional Ingredient(s)

[0211] 4. An anti-aging ingredient such as: [0212] SENESTEM™, marketed by Sederma, comprising plant cells obtained by in-vitro cell culture of Plantago lanceolata, which in particular improves the viscoelastic properties of the skin and lightens the pigmentary spots of senescence. [0213] 5. An antioxidant agent such as: [0214] MAJESTEM™, marketed by Sederma, based on Leontopodium alpinum plant cells obtained by in-vitro cell culture titrated in leontopodic acid; neutralizes oxidative stress (pollution, UV radiation) and restores skin tension.

[0215] 3) Gel Form

TABLE-US-00022 TABLE 22 Raw materials INCI name Function % Part A: H.sub.2O / / qsp100 Carbomer / Rheology 0.40 modifier Part B: Glycerin Glycerin Humectant 7.00 Phenoxyethanol Phenoxyethanol Preservative 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 ™ Di-PPG-2 Myreth-10 Emollient 1.00 SCE Adipate Covi-ox ™ Tocopherol (and) Antioxidant 0.40 Helianthus Annuus (Sunflower) Seed Oil Part E: Ingredient according / Active 3.00 to the invention

Example(s) of Additional Ingredient(s)

[0216] 6. an “antipollution” ingredient such as: [0217] CITYSTEM™, marketed by Sederma, based on plant cells obtained in vitro of Marrubium vulgare with a high concentration of Forsythoside B; used against pollution attacks: makes the skin soft and smooth, refines the skin texture, reduces the visibility of comedones, leaving the skin radiant and purified. [0218] 7. a calming ingredient for sensitive skin such as: [0219] PACIFEEL™, marketed by Sederma, comprising an extract of Mirabilis Jalapa. [0220] 8. An hydrating ingredient such as: [0221] AQUALANCE™, marketed by Sederma, osmoprotective hydrating active ingredient composed of homarin and erythritol.

[0222] 4) Gel Form to Realise a Spray Mask

TABLE-US-00023 TABLE 23 Raw materials INCI name Function % Part A: H.sub.2O / / qsp100 Hydrotriticum Aqua (and) Hydrolyzed Film forming 3.00 PVP PE ™ Wheat Protein/PCP agent 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) Antioxidant 0.20 Helianthus Annuus (Sunflower) Seed Oil Part D: H.sub.2O / / 2.50 NaOH 30% Sodium Hydroxide pH adjuster 0.25 Part E: Ingredient according Active 3.00 to the invention

Example(s) of Additional Ingredient(s)

[0223] 9. an ingredient that acts on the radiance of the complexion such as: [0224] EVERMAT™, marketed by Sederma, comprising a combination of an extract of Enantia chlorantha rich in protobberins and oleanolic acid; decreases pore size and shining; refines the texture of acne-prone skin. [0225] 10. an ingredient with revitalizing properties such as: [0226] Fruitliquid™ Kumquat™, marketed by Crodarom.

[0227] 5) Cream Form, for a Make-Up Base

TABLE-US-00024 TABLE 24 Raw materials INCI name Function % Part A: H.sub.2O / / qsp 100 Volarest ™ FL Acrylates/Beheneth-25 Rheology 0.90 Methacrylate modifier Copolymer Part B: Arlacel ™ 2121 Sorbitan Stearate (and) Emulsifier 4.50 Sucrose Cocoate) Part C: Pentylene glycol Pentylene Glycol Humectant 5.00 Phenoxyethanol Phenoxyethanol Preservative 0.80 Part D: Crodamol ™ SSA Decyl Isostearate (and) Emollient 2.00 Isostearyl 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 ™ Antioxidant 0.10 Tocopherol (and) Helianthus Annuus (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 according Active 3.00 to the invention

Example(s) of Additional Ingredient(s)

[0228] 11. A concealer/eye contours ingredient such as: [0229] HALOXYL™, marketed by Sederma, combination of 2 matrikines, Pal-GHK and Pal-GQPR with N-hydroxysuccinimide and a flavonoid, the chrysin. [0230] EYELISS™, marketed by Sederma, combines three components: hesperidin methyl chalcone, the dipeptide Valyl-Tryptophan (VW) and the lipopeptide Pal-GQPR. [0231] PRODIZIA™, marketed by Sederma, comprising an extract of Albizia julibrissin, which promotes the visible reduction of signs of fatigue: dark circles, under eyes bags, dull complexion and drawn lines by repairing and protecting the skin from damage caused by glycation. [0232] 12. An anti-wrinkle/anti-aging ingredient based on peptide(s) such as: MATRIXYL 3000™ [0233] MATRIXYL synthe'6™ and/or MATRIXYL Morphomics™, marketed by Sederma.