Peptide-based cosmetic or dermatological treatment of the skin and its appendages

Abstract

To provide the use of a peptide for non-therapeutic cosmetic treatment of the keratinous tissue of the skin and its appendages.SOLUTION: Use of at least one peptide having the general formula X - (Xaa) nK * TTK * X ' aa - (Xaa) m-Z is provided. Wherein K * is independently selected from lysine and the like; (Xaa) n and (Xaa) m independently correspond to a sequence of n or m amino acids Xaa; N and m are independently an integer between 0 and 5; X' aa is selected from threonine and serine; X, which is the N-terminus, is selected from H, - CO-R1, - SO2-R1, or a biotinoyl group; Z, which is the C-terminus, is selected from OH, OR1, NH2, NHR1, or NR1R2; R1 and R2 independently have 1 to 24 carbon atoms; It may have one or more heteroatoms of O, S and / or N in its backbone. A preferred peptide is Pal-KTTKS.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to the peptide(s)-based cosmetic or dermatological treatment of mammalian, human or animal, skin and its appendages.

[0002] More particularly, the present invention relates to the cosmetic, dermatological, hygiene, and personal care product industries. [Background technology]

[0003] Peptides have important signaling functions and regulate many biochemical processes, making them indispensable and promising active ingredients, more particularly in the cosmetics industry, where new compounds capable of beautifying the skin and its appendages are constantly being searched for in order to improve their normal condition.

[0004] Most of the peptides currently proposed are peptides that act on the dermis by stimulating extracellular matrix components, mainly collagen and elastin. A large number of peptides have been proposed in this field, particularly by the applicant. For example, Pal-KTTKS (SEQ ID NO 1), sold under the trademark Matrixyl®, a mixture of Pal-GHK and Pal-GQPR (SEQ ID NO 2), sold under the trademark Matrixyl® 3000, Pal-KMO2K (MO2 corresponds to methionine dioxide), sold under the trademark Matrixyl® Synthe' 6®, and more recently Pal-K(P)HG (with proline grafted to lysine), sold under the trademark Matrixyl® Morphomics™, Pal-VGVAPG (SEQ ID NO 3), sold under the trademark Dermaxyl™ or Biopeptide EL™. 3), or N-acetyl-Tyr-Arg-O-hexadecyl ester sold under the trademark Idealift™ or Calmosensine™.

[0005] However, the beauty and health of skin also depend heavily on the quality and thickness of the epidermis, particularly through optimal differentiation of keratinocytes and the ability of the epidermis to form its outermost layer, the stratum corneum, and through its periodic renewal through desquamation. The epidermis, particularly the stratum corneum, actually forms a natural skin barrier essential for protection against external environmental molecules and attacks (e.g., photoirradiation, pollutants, etc.). For example, a strong skin barrier can limit the risk of epidermal microinflammation, which can cause premature skin aging. This protection is even more necessary for sensitive skin. It also limits the risk of moisture loss and helps maintain good epidermal hydration. In addition to this physical barrier, there is also a chemical barrier formed by antimicrobial peptides synthesized by keratinocytes. The role of antimicrobial peptides is to protect the skin from pathogenic bacteria. Maintaining and improving this chemical barrier function is important.

[0006] Furthermore, the skin microbiota is a highly complex ecosystem consisting of a collection of living microorganisms (bacteria, yeasts, viruses, and parasites) with various functions, such as defense, skin barrier, and immune system regulation. It is important to maintain the balance of the skin microbiota by preventing the excessive proliferation of certain microorganisms that can damage the skin, for example, in the case of yeasts of the genus Malassezia, which are involved in dandruff conditions, and the acne bacterium Propionibacterium acnes (recently renamed Cutibacterium acnes). Although P. nematoides is part of the normal microflora of the skin, its rapid proliferation is thought to promote keratinocyte proliferation and migration, contribute to the formation of radical species such as superoxide anions, and trigger a cascade of reactions that result in the production of pro-inflammatory molecules, contributing to acne development.

[0007] Malassezia yeasts are also part of the normal scalp flora, and when these yeasts multiply quickly enough, they cause the condition dandruff.

[0008] Therefore, it is important to maintain a balance in the skin microflora. Summary of the Invention

[0009] It is an object of the present invention to provide peptides that have activity on keratinous tissue, in particular the epidermis and appendages of the skin, such as nails, hair, and body hair (including eyelashes and eyebrows). In particular, it is an object of the present invention to provide peptides that can act on the stratum corneum, i.e., the first superficial layer of the skin, thereby meeting the aforementioned needs.

[0010] To this end, firstly, the invention provides the use of at least one peptide of general formula 1 below for the non-therapeutic cosmetic treatment of the keratinous tissue of the skin and its appendages.

[0011] X-(Xaa) n K * TTK * X'aa-(Xaa) m -Z...Formula 1

[0012] In general formula 1: ·K * is selected from lysine (Lys, K), hydroxylysine, ornithine (Orn), diaminobutyric acid (Dab), or diaminopropionic acid (Dap), or a formylated, acetylated, trifluoroacetylated, methanesulfonylated, or succinylated derivative thereof, and both K * are the same or different; (Xaa) n and (Xaa) m corresponds independently to a sequence of n or m amino acids Xaa selected independently from glycine (Gly, G), alanine (Ala, A), proline (Pro, P), valine (Val, V), leucine (Leu, L), isoleucine (Ile, I), and phenylalanine (Phe, F), where n and m are integers between 0 and 5, which may be equal or different; X'aa is selected from threonine (Thr, T) and serine (Ser, S); The N-terminal X is H, -CO-R 1 , -SO2-R 1 or a biotinoyl group; The C-terminal Z is OH, OR 1 , NH2, NHR 1 , or NR 1 R 2 Selected from; ·R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfurized, and which have from 1 to 24 carbon atoms and may have one or more O, S, and / or N heteroatoms in their backbone.

[0013] The present invention maintains or improves the condition of the epidermis and its appendages (nails, hair, body hair, etc.) particularly through its action on keratinocytes.

[0014] The peptides used according to the invention contain the amino acid sequence K, which is a physiologically active sequence on keratinocytes. * TTK * It is characterized in that it contains at least X'aa, and X'aa is T or S. Active sequence K * TTK * At either end of X'aa, a sequence of 1 to 5 nonpolar amino acids selected from Gly, Ala, Pro, Val, Leu, Ile and Phe, preferably selected from Gly, Ala and Phe, more preferably selected from Gly and Ala, may be added.

[0015] Preferably, the derivative is an acetylated derivative, and more preferably, the derivative is an acetylated derivative, and the first K at the N-terminus of the peptide is * It comes from the modification of

[0016] According to the present invention, preferably, K * is lysine (K) or ornithine, more preferably lysine.

[0017] According to the present invention, more preferably, n and m are 0, 1 or 2, preferably 0, and the peptide has the general formula 2:

[0018] XK * TTK * X'aa-Z (SEQ ID NO 4)...Formula 2

[0019] Preferably, the peptide according to the invention has the general formula 3:

[0020] X-KTTKX'aa-Z…Formula 3

[0021] X, Z, and X'aa are as defined above.

[0022] A preferred example is X-KTTKS-Z, more preferably Pal-KTTKS (SEQ ID NO 1). Another example of a preferred peptide is Pal-GKTTKS (SEQ ID NO 5).

[0023] The results of in vitro tests on keratinocyte cultures are described below, which show that the peptides according to the invention allow for the maintenance / protection and improvement of the epidermal condition, for example by strengthening the skin barrier function and harmonizing the natural process of epidermal maturation.

[0024] Proteomics and DNA-array results are also presented in the detailed description below, which confirm their effect on the epidermis and further demonstrate the action of at least one peptide according to the invention on keratinocyte-based appendages such as hair, body hair (including eyelashes and eyebrows) and nails, as well as anti-acne activity.

[0025] Furthermore, the specific and significant effect of the peptides according to the invention on Propionibacterium acnes has been demonstrated in two tests on cultures of this bacterium.

[0026] All these studies demonstrated the targeted action of the peptides according to the invention at several levels, in particular: Stimulating the production of several molecules that constitute the skin barrier or play a positive role in the differentiation of keratinocytes at the barrier's origin; -Improvement of regeneration of the stratum corneum through desquamation; Stimulating the production of alpha-crystallin to protect the skin from UV, inflammatory, and oxidative attack; - Reducing the amount of certain molecules involved in micro-inflammation of the skin caused by various small everyday insults (light irradiation, pollutants, etc.); · Improved hydration of the upper epidermis by reducing transepidermal water loss (TEWL); Treating epidermal scars, in particular their reduction, and in particular treating acne scars or blemishes on the epidermis; Action against acne-causing bacteria (Propionibacterium acnes) and dandruff yeast (Malassezia); Action on hair and body hair, improving hair strength and growth; Action on nails; -Anti-inflammatory (prevents inflammation).

[0027] Thus, the treatment according to the invention: Maintaining, protecting, and / or improving the condition of the epidermis by strengthening the skin's barrier function and harmonizing the natural process of epidermal maturation; and / or Protecting the skin and its appendages from external environmental molecules and aggressors, including defenses against bacteria, inflammation, and radiation; and / or Improve hydration of the upper epidermis by reducing transepidermal water loss (TEWL); and / or Treating epidermal scars, in particular treating epidermal acne scars, in particular reducing the appearance and visibility of scars; and / or · Beautifying nails, hair, and body hair (including eyelashes and eyebrows); and / or combats acne and / or dandruff microorganisms, It is adapted to:

[0028] These results therefore demonstrate that the use of peptides according to the present invention is particularly advantageous for the treatment of oily and / or acne-prone skin through a preventive action. This skin type often corresponds to the oily skin of teenagers, which is caused by excessive sebum due to hormones. Preventing or limiting the proliferation of Propionibacterium acnes bacteria first prevents the generation of waste products in the hair follicle sheath. There, the bacteria feed on sebum, grow anaerobically, and produce waste products, particularly dead cells. This in turn leads to damage to the hair follicle sheath (the formation of black spots) and inflammation, which ultimately leads to acne breakouts, the treatment of which falls within the scope of dermatology. Therefore, reducing the number of Propionibacterium acnes bacteria can prevent the progression to acne-prone conditions, particularly pro-inflammatory conditions.

[0029] Furthermore, from a non-therapeutic cosmetic point of view, the use of the peptides of the invention has shown results that are particularly suitable and advantageous for the treatment (reducing the effects) of unsightly skin acne scars or marks that remain after an acne outbreak, through the regeneration of the epidermis, which results in a soft and natural smoothing treatment.

[0030] Preferably, the peptides according to the invention are modified at either the N-terminal or C-terminal position, preferably only at the N-terminal position.

[0031] According to another preferred feature of the present invention: ·R 1 and / or R 2 is an alkyl chain of 1 to 24 carbon atoms, preferably a lipophilic alkyl chain of 3 to 24 carbon atoms; and / or X is an acyl group CO-R1 is preferably selected from octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl, and lipoyl; more preferably selected from lauroyl (C12), myristoyl (C14), and palmitoyl (C16); and / or Z is selected from OH, OMe, OEt, and NH2, preferably OH; and / or X is selected from palmitoyl (C16), myristoyl (C14) and lauroyl (C12); more preferably palmitoyl (C16) and Z is OH; and / or ·X'aa is serine.

[0032] Peptides containing acid derivatives such as ascorbic acid, retinoic acid, cinnamic acid, oleanolic acid, hyaluronic acid, nicotinic acid, lipoic acid, gallic acid, or pantothenic acid at the N- or C-terminal position are also encompassed by the present invention.

[0033] A preferred peptide according to the invention is Pal-KTTKS-OH (Pal-KTTKS, INCI name: Palmitoyl pentapeptide-4, marketed as Matrixyl®, SEQ ID NO 1), which corresponds to a substitution with a palmitoyl chain at the N-terminus (X=Pal) and no substitution at the C-terminus (Z=OH).

[0034] The peptides according to the present invention may be optically pure and may consist of the L- or D-isomer, or a mixture thereof. The naturally occurring L-isomer may be preferred. The peptides may optionally be in the form of a salt, for example, a hydrochloride or acetate salt.

[0035] The present invention also encompasses peptide derivatives (with altered and / or added chemical functions but without altered carbon backbones), peptide analogs (with altered and / or added chemical functions and altered carbon backbones), and complexes with other species such as metal ions (e.g., copper, zinc, manganese, magnesium, and others).

[0036] For use according to the invention, the peptides can be dissolved in a physiologically acceptable lipophilic or hydrophilic matrix, optionally with the aid of solubilizing agents, depending on the form of administration envisaged.

[0037] "Physiologically acceptable" medium means, but is not limited to, an aqueous or aqueous-alcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, an aqueous gel, an anhydrous gel, a serum, a vesicle dispersion, or a powder in the present invention.

[0038] "Physiologically acceptable" means that ingredients and compositions containing the peptides according to the present invention can be ingested or injected into the skin without risk of toxicity, incompatibility, instability, allergic reaction, etc., and are suitable for topical or transdermal use in contact with the mucous membranes, nails, scalp, hair, body hair and skin of mammals, more particularly humans. This "physiologically acceptable medium" forms what is generally called the excipient of the composition.

[0039] The peptides according to the invention may also be used in vectorized form by being bound, entrapped or absorbed in macro-, micro- or nano-particles such as capsules, spheres, liposomes, oleosomes, chylomicrons, sponges, in the form of micro- or nanoemulsions, or by being adsorbed onto, for example, powdered organic polymers, talc, bentonite, spores or exines, and other inorganic or organic supports.

[0040] Thus, the present invention also provides, secondly, the use of at least one peptide as defined above for the preparation of a composition for the treatment of the keratinous tissue of the skin and its appendages.

[0041] The composition comprising the peptide according to the invention may be provided in any galenical form (examples of which are given in the following description) and may be delivered via a textile support made of natural fibres, synthetic fibres, wool or any material adapted to come into contact with the skin, or may be applied to clothing such as daytime or nighttime underwear, handkerchiefs or textiles, so as to exert a cosmetic or dermatological effect upon contact with the skin / textile and allow continuous topical delivery.

[0042] In a particularly advantageous form, according to the invention, the peptide acts as an enhancer of activity The active ingredient may be combined with at least one additional active agent adapted to act in a complementary manner to one or more other activities.

[0043] To this end, various additional active agents are described in the detailed description below.

[0044] Third, there is also provided a method for improving the aesthetic appearance of the skin and its appendages, comprising topically applying to the skin an effective amount of a composition comprising at least one peptide according to the present invention.

[0045] In the case of dermatological compositions, the above-described method may be suitable for antimicrobial (antibacterial and / or antifungal) and / or anti-inflammatory treatments. This is due to the inhibitory effect of the peptides on the growth curve of Propionibacterium acnes, as described above, and the strong stimulation associated with the expression of numerous antimicrobial peptides (PAMs). Antimicrobial peptides can inhibit the growth of Malassezia yeasts, which cause dandruff, in particular, by repairing the skin's defense systems (anti-inflammatory and immune) against bacteria, oxidants, and radiation, reconstructing the skin barrier, and enhancing moisturization.

[0046] Fourthly, therefore, the present invention also provides a peptide for therapeutic treatment, which comprises applying an effective amount of the peptide according to the present invention to skin in need thereof. The treatment is in particular antimicrobial (antibacterial or antifungal) and / or anti-inflammatory. The treatment is particularly suitable for soothing sensitive and irritated skin and / or for treating acne, psoriasis, dermatitis, and eczema.

[0047] According to the invention, said peptide is adapted for use in the preparation of a cosmetic composition for treating acne-prone skin and / or moisturizing the skin and / or smoothing the skin and / or preventing the occurrence of dandruff and / or protecting the skin microflora and / or strengthening skin immunity.

[0048] "Topical treatment" or "topical use" means, according to the invention, an application intended to act where it is applied, ie on the skin, mucous membranes and appendages.

[0049] The peptides according to the invention or compositions comprising the peptides can be applied topically to the target area.

[0050] An "effective" amount depends on various factors, such as the age and condition of the patient, the severity of the disorder, and the mode of administration, etc. An effective amount means a non-toxic amount sufficient to achieve the desired effect.

[0051] To be present in an effective amount, in the cosmetic composition according to the invention, the at least one peptide is generally found in a proportion ranging from 0.01 ppm to 500 ppm, preferably from 0.1 ppm to 50 ppm, more preferably from about 1 ppm to 10 ppm relative to the total weight of the composition, depending on the purpose of the composition and the desired effect, which may be more or less pronounced.

[0052] All percentages and ratios used herein are by weight of the total composition and all measurements are made at 25°C unless otherwise specified.

[0053] For example, for facial cosmetic procedures, the European Cosmetics Directive recommends a limit of 2.72 mg / cm per person. 2 The standard application amount of cream per day is 0.5 mg / cm per person. 2 A standard application amount of body lotion per day has been set.

[0054] According to another feature, the cosmetic treatment method according to the present invention may be combined with one or more other treatment methods that target the skin, such as, for example, light therapy, thermotherapy, vibration therapy, electrotherapy, microneedle patches or aromatherapy treatments.

[0055] According to the present invention, it is possible to provide a device or kit with several compartments intended for carrying out the methods described above, which may contain, for example but not limited to, a composition comprising one or more peptides according to the invention in a first compartment and excipients and / or additional active agents in a second compartment, wherein the compositions contained in the first and second compartments are considered in particular as a combined composition for simultaneous, separate or stepwise use in one of the treatment methods described above.

[0056] The compositions according to the invention, in appropriate doses, are also suitable for therapeutic treatment, in particular for the treatment of skin, in particular for the treatment of skin with a diseased epidermis.

[0057] The present invention will be better understood with reference to the following description of embodiments and in vitro and in vivo tests.

[0058] A) Example of preparation of Pal-KTTKS peptide (SEQ ID NO 1) according to the invention The Pal-KTTKS peptide is prepared by peptide synthesis. Serine is coupled to a resin via its terminal acid function (using a coupling agent, e.g., DCC (dicyclohexylcarbodiimide) / NHS (N-hydroxysuccinimide) or HBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) / HOBT (1-hydroxybenzotriazole)). The protected serine is then reacted with a lysine derivative in the presence of a coupling agent, followed by the addition of two threonines and, in the same procedure, a second lysine. The latter is then acylated at its amine function with an activated palmitic acid derivative (e.g., palmitoyl chloride) in the presence of a base. After cleavage of the peptide chain from the resin in an acidic medium, precipitation, washing and drying, palmitoyl-lysyl-threonyl-threonyl-lysyl-serine is obtained in solid form.

[0059] B) Preparation example of a cosmetic active ingredient according to the invention containing Pal-KTTKS (SEQ ID NO 1) The Pal-KTTKS peptide is amphiphilic: the Pal chain is hydrophobic and the peptide portion is hydrophilic. The peptide is solubilized in a water / glycol matrix using a suitable surfactant, e.g., at 100 ppm.

[0060] To practice the present invention, the commercially available ingredient Matrixyl®, which contains Pal-KTTKS (palmitoyl pentapeptide-4), may be used.

[0061] C) Efficacy Testing Efficacy tests were carried out on Pal-KTTKS, a preferred peptide according to the invention, in solution in an inert solvent (ethanol) at the recommended concentration for use on the skin.

[0062] The following in vitro tests were performed on normal human keratinocytes (NHK), epidermal cells, and on cultures of the bacterium Propionibacterium acnes.

[0063] The various test methods used are as follows: Molecular biological testing of NHK cultures principle: In this test, confluent keratinocytes are contacted with the peptides according to the invention for 24 hours. The cells are then lyophilized, their RNA extracted, converted to DNA, and then analyzed by qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction). The results are expressed as the expression ratio between treated and control cases. A ratio greater than 1.5 (control + 50%) indicates induced gene expression. Analysis of variance and Student's t-test are performed to assess the significance of the results (n=4 for each condition).

[0064] Immunoenzyme assay test of NHK culture medium principle: Cultured and confluent NHKs are exposed to the peptides of the present invention (or their solvent) for 24 hours in a medium that allows their survival. The cell layer is then irradiated with UVB in a physiological buffer and returned to contact with the test article for 24 hours. At the end of this incubation period, the medium is analyzed by ELISA to determine the amount of proinflammatory mediators produced by these cells in response to irradiation. The results are compared with those of the control. Cellular respiration tests are performed on fixed mats to assess cell number and normalize the results. Analysis of variance and Student's t-test are performed to assess the significance of the results.

[0065] Testing NHK culture medium using DNA microarray technology (DNA-array) principle: The peptides of the present invention (7 ppm) were contacted with confluent NHKs for 24 or 48 hours (vs. control). The NHK mats were then washed, the cells disrupted, and their mRNA extracted. These mRNAs were then deposited on a DNA chip and amplified using a method similar to QRT-PCR, then converted into small DNA sequences for analysis. The changes in mRNA induced by the peptides were compared with those in the control (peptide solvent). The results were expressed as the expression ratio between the treated and control samples. A ratio greater than 1.5 (control ratio + 50%) was considered to indicate induction of gene expression.

[0066] Examination of NHK broth by liquid chromatography / mass spectrometry (LC-MS / MS) principle: The same incubation procedure as for DNA arrays was used, but the incubation time was extended (7 days) because it takes time for protein production to become detectable by this LC-MS / MS method. The peptide concentration used in the cells was 5 ppm (vs. control). NHK medium (n=3) was changed every 3 days. After the end of this contact period, the cells were lysed, and proteins were extracted and analyzed in the form of lysates by a method that combines the action of proteases on the lysates, separation of the fragments by liquid chromatography combined with mass spectrometry, and analysis of the identity and concentration of the existing proteins according to the nature and quantity of the obtained fragments (LC-MS / MS). The protein concentration of the lysates was measured for LC-MS / MS analysis of equivalent amounts of protein. The results were expressed as the expression ratio between the treated and control samples. A ratio greater than 1.5 (control + 50%) was considered to indicate increased protein production. Analysis of variance and Student's t-test were performed to assess the significance of the results.

[0067] Immunofluorescence labeling of KHN culture fluids principle: Confluent NHKs (n=3) were cultured for 7 days as described above in the presence or absence (control) of the peptides according to the invention, after which the cell layer was fixed and subjected to immunocytochemical labeling using antibodies against proteins characteristic of epidermal maturation: involucrin, loricrin, and filaggrin. Photographs were taken using a fluorescence microscope and the images were analyzed appropriately. The results are analyzed using standard software. The results are compared with the control. The number of cells on the mat is assessed by the Hoechst method (DNA staining) by reducing the fluorescence value to the cell number. Analysis of variance and Student's t-test are performed to assess the significance of the results.

[0068] Propionibacterium acnes growth inhibition test principle: Suspensions of Propionibacterium acnes at equivalent densities are cultured in the appropriate medium at 37°C under anaerobic conditions in the presence (test samples) or absence (control samples) of a peptide according to the present invention. Samples are taken at regular intervals and the OD at 600 nm is measured to track bacterial growth over time. A growth curve for each culture is thus established.

[0069] 1. Improves epidermal barrier and harmonizes epidermal maturation The cornified layer or stratum corneum is a highly complex assembly of flat, anuclear cells that are tightly bound together on the one hand, and lipids and proteins on the other, whose composition and assembly ensure the unique properties of this structure, which make it highly resistant to physical, chemical and biological attacks from the environment.

[0070] The test results presented below show that the peptides according to the invention improve epidermal homeostasis and strengthen the skin barrier by analyzing various markers involved in epidermal differentiation and barrier formation.

[0071] Keratinocytes gradually mature by acquiring a very strong outer shell formed by interconnected proteins called involucrin and loricrin through the intervention of the calcium-sensitive enzyme transglutaminase. Furthermore, other proteins involved in the maturation and homeostasis of the stratum corneum, SPRRs (small proline-rich region proteins), further strengthen this protein shell by forming flexible and strong crosslinks between proteins through the activity of transglutaminase. LCEs (late cornified envelope proteins) are also one of the last components to be crosslinked during maturation. Furthermore, ceramides are crucial for the formation of the stratum corneum and its proteolipid matrix, and therefore cosmetic active ingredients that stimulate the synthesis of these components are also important.

[0072] Furthermore, a good barrier function is highly dependent on filaggrin produced by keratinocytes, which undergoes significant metabolism: it stabilizes the corneocyte by binding to keratin and is eventually degraded into amino acids, which become essential components of the natural moisturizing factors (NMF) present in the stratum corneum, enabling good skin hydration.

[0073] Furthermore, kallikrein is a protease involved in the renewal of the stratum corneum, allowing the natural desquamation of the stratum corneum, thereby ensuring a gentle "natural" smoothing effect. Increased expression and synthesis of these enzymes may improve the natural process of desquamation of the stratum corneum, mimicking natural peeling.

[0074] 1.1. Effects on epidermal differentiation and stratum corneum formation

[0075] 1.1.1. Induction of involucrin, loricrin, and filaggrin formation in NHK (by immunofluorescence) / Effect of 5 ppm of the peptide according to the invention

[0076] [Table 1]

[0077] 1.1.2. Changes in the expression of genes (DNA arrays) encoding proteins of epidermal differentiation and stratum corneum formation compared to controls / Effect of 7 ppm of the peptide according to the invention after 24 or 48 hours of contact

[0078] [Table 2]

[0079] 1.1.3. Changes in proteins related to epidermal maturation compared to the control (by LC-MS / MS) / Effect of 5 ppm of the peptide according to the invention

[0080] [Table 3]

[0081] 1.1.4. Changes in gene expression of involucrin and transglutaminase 1 compared to control up to 24 hours (by RT-PCR) / Effect of 5 ppm of the peptide according to the invention

[0082] [Table 4]

[0083] 1.2. Effect on the formation of lipid lamellar bodies Changes in the expression of genes (DNA array) encoding proteins involved in the formation of the lipid keratinocyte compared to the control / Effect of 7 ppm of the peptide according to the invention after 24 or 48 hours of exposure

[0084] [Table 5]

[0085] 1.3. Effects on the formation of desmosomes, corneodesmosomes, and tight junctions Changes in the expression of genes (DNA arrays) encoding proteins involved in the formation of desmosomes, corneodesmosomes, and tight junctions compared to controls / effect of 7 ppm of the peptide according to the invention after 24 hours of exposure

[0086] [Table 6]

[0087] 1.4. Control of desquamation Changes compared to controls in the expression of genes (DNA arrays) encoding proteins involved in the regulation of desquamation / effect of 7 ppm of the peptide according to the invention after 24 hours of contact

[0088] [Table 7]

[0089] conclusion : The peptides according to the invention appear to act at all levels tested: from filaggrin metabolism to the regulation of desquamation, including the production of stratum corneum components, the formation of lipid lamellar bodies, and the formation of tight junctions that improve and strengthen the epidermal barrier.

[0090] The peptides according to the invention therefore act advantageously to guarantee the maintenance of epidermal homeostasis, ensuring a good balance between cell regeneration by differentiation and the formation of a quality skin barrier effective in particular against external aggressions. This type of activity profile guarantees a good re-epithelialization of the skin tissue in subjects suffering from acne, by reducing unaesthetic acne scars.

[0091] 2. Skin protection, including defense against bacteria, inflammation, radiation, and immune stimulation

[0092] 2.1. Human beta-defensin 3 (HBD3) and other markers HBD3 is an antimicrobial peptide that acts at several levels. It is a key molecule in the skin's immune system. In particular, HBD3 has a broad spectrum of destructive properties against bacteria and yeasts. Therefore, stimulating the expression of this peptide has attracted considerable interest in cosmetics for the prevention and treatment of acne (against Propionibacterium acnes) and for the treatment of dandruff conditions (against Malassezia yeasts). Recently, these antimicrobial defense peptides have been shown to have a broader range of actions in the skin, playing a role in regulating inflammatory responses by regulating cell proliferation, migration, and differentiation, the production of various cytokines, the development of epidermal scar formation, and improving barrier function.

[0093] The peptide according to the present invention has an anti-inflammatory role accompanied by induction of the anti-inflammatory cytokine IL-37, and this role has been demonstrated by DNA array analysis. Furthermore, it has been reported that this peptide is involved in skin immunity through the production of various cytokines / chemokines. Furthermore, it has also been reported that this peptide counteracts the inflammatory effects of bacterial lipopolysaccharides. Finally, it has been reported that this peptide exerts feedback control over inflammatory activity by inhibiting the TLR (Toll-like receptor) pathway.

[0094] Thus, the peptides according to the invention, including in cosmetic compositions, are able to strongly stimulate the gene expression of human beta-defensin 3, which is essential for the innate immune system, and thus have a protective effect against the invasion or proliferation of infectious agents in the skin, which is not pathogen-specific but acts immediately in the form of an inflammatory response.

[0095] The peptides according to the invention also stimulate the gene expression of SOD2, which is important in the skin's defense against free radicals (here, superoxide radicals).

[0096] The direct action against Propionibacterium acnes raises the interest of the peptides according to the invention for combating acne.

[0097] result : Changes in gene expression (DNA array) encoding proteins involved in skin protection compared to controls / effect of 7 ppm of the peptide according to the invention after 24 or 48 hours of contact

[0098] [Table 8]

[0099] Changes in proteins involved in skin protection compared to the control (by LC-MS / MS) / Effect of 5 ppm of peptide according to the invention.

[0100] [Table 9]

[0101] 2.2.Specific activity against Propionibacterium acnes Growth of Propionibacterium acnes: time required to reach an OD of 1 in control cases and in the presence of peptides according to the invention (N=2 independent experiments; n=2 cultures / case).

[0102] [Table 10]

[0103] These data show that the peptides according to the invention potently and dose-dependently inhibit the growth of Propionibacterium acnes.

[0104] 2.3.α-Crystallin Alpha-crystallin is a small protein related to the HSP family (or heat shock proteins). Alpha-crystallin is present in the epidermis, where it protects epithelial cells, restores mitochondrial function, and increases resistance to oxidative stress. This protein has the property of being present within and in close proximity to cells. Therefore, its presence protects the skin from UV rays, inflammation, and more generally, oxidative attack.

[0105] Change in gene expression of α-crystallin B (by RT-PCR) compared to control between 1 and 24 hours / effect of 5 ppm of peptide according to the invention.

[0106] [Table 11]

[0107] Changes in proteins involved in skin defense compared to controls ( LC-MS / MS ) / Effect of 5 ppm of the peptide according to the present invention.

[0108] [Table 12]

[0109] 2.4. Reduced production of inflammatory markers Skin is exposed to constant stresses (such as exposure to UV rays, smoke, and pollutants), some of which can trigger direct or indirect inflammatory responses. Uncontrolled or constant inflammatory responses, although low in intensity, induce the production of cytokines such as IL-1α, IL-1β, IL-6, and TNFα, and lipids such as PGE2, which attract or stimulate other cells, resulting in a cascade reaction. The pro-inflammatory microenvironment thus formed alters skin homeostasis, gradually altering or even destroying biomolecules in cells and tissues. It also induces disruption of the integrity of the skin barrier. Thus, the inflammatory mediators IL-6 and PGE-2 are known to cause premature aging through microinflammation. Furthermore, sensitive, inflammatory skin is characterized by abnormally high secretion of cytokines, pro-inflammatory peptides (e.g., IL-1 and IL-6), and pro-inflammatory lipids (e.g., PGE-2).

[0110] To test active ingredients, keratinocytes were cultured under mild stress conditions (application of UVB radiation) to mimic experimental skin microinflammation. In this context, a significant reduction in the secretome of inflammatory mediators is interpreted as a skin repair and protective effect.

[0111] result : Changes in the secretome of pro-inflammatory mediators by NHK exposed to UVB compared to controls (by immunoenzymatic measurement) / Effect of 4 ppm, 6 ppm and 8 ppm of the peptide according to the invention.

[0112] [Table 13]

[0113] These results show a very interesting effect of the peptides according to the invention to attenuate the secretion of pro-inflammatory mediators by NHKs exposed to UVB radiation, which is particularly interesting for sensitive skin, where inflammation occurs due to radiation and exposure to various pollutants, which cause microinflammation.

[0114] In addition to these results, the expression of the above-mentioned IL37 gene was also confirmed.

[0115] conclusion : The peptides according to the invention are regulating in the sense that they strengthen the skin's defenses against bacteria, oxidants, radiation and the resulting inflammation, and all the markers tested act towards this end.

[0116] 3. Action on the prevention and treatment of epidermal scars Human beta-defensin 3 is involved in scar formation by promoting keratinocyte migration and proliferation. These actions involve the induction of phosphorylation of the signal transduction factor EGFR, as well as STAT1 and STAT3, intracellular signaling molecules known to be involved in keratinocyte migration and proliferation.

[0117] Certain tight junction (TJ) proteins, such as occludin, are also involved in keratinocyte migration and proliferation, processes that are essential for normal skin wound healing and epidermal regeneration.

[0118] The signaling pathway of BMPs, members of the TGFβ superfamily, regulates the healing process by directing keratinocytes toward proliferation or differentiation, depending on the stage of healing.

[0119] Changes compared to controls in the expression of genes (DNA-array) encoding proteins involved in scar formation / effect of 7 ppm of the peptide according to the invention after 24 or 48 hours of exposure.

[0120] [Table 14]

[0121] Changes in proteins involved in healing compared to the control (measured by LC-MS MS) / Effect of 5 ppm of peptide according to the invention.

[0122] [Table 15]

[0123] Conclusion: All the markers tested indicate that the peptide according to the invention acts at the level of the keratinocytes by improving the healing process.

[0124] 4. Beneficial effects on nails and hair

[0125] 4.1.Effect on nails BMPs, members of the TGFβ superfamily, are involved in nail differentiation and development. By activating transcription factors, BMPs promote communication between the epidermis and mesenchyme and regulate differentiation.

[0126] Changes compared to controls in the expression of genes (DNA array) encoding nail constituent proteins or proteins involved in nail formation / effect of 7 ppm of the peptide according to the invention after 24 or 48 hours of contact.

[0127] [Table 16]

[0128] Changes in nail constituent proteins or proteins involved in nail formation compared to controls ( Measurement by LC-MS / MS ) Effect of 5 ppm of the peptide according to the present invention.

[0129] [Table 17]

[0130] Conclusion: It was found that the gene expression and / or concentration of some compounds involved in nail formation and nail itself increased after contact with the peptides according to the present invention, as confirmed by DNA-array and LC-MS / MS protein studies.

[0131] Therefore, the compounds according to the invention appear to be entirely desirable for maintaining healthy nails or treating damaged nails.

[0132] 4.2. Effects on hair Hair follicle morphogenesis and the initiation of anagen in resting hair follicles are characterized by the activation of different signaling pathways as a result of the construction of the hair shaft. Among these, the balance between the activity of the Wnt / β-catenin pathway and the BMP pathway is particularly important.

[0133] Therefore, BMPs are involved in the regulation of hair growth by suppressing the proliferation phase of dermal papilla cells and stimulating the differentiation of cells that synthesize hair shafts. Conversely, the Wnt / β-catenin pathway results in the activation of dermal papilla cell proliferation.

[0134] Trichohyalin is expressed in certain epithelia that are particularly mechanically strong, such as the cells of the inner sheath of the hair follicle. Trichohyalin is modified by enzymes, particularly transglutaminases, to introduce intra- and inter-protein cross-links. Trichohyalin is a multifunctional protein cross-linked by bridges that function within the inner root sheath of hair, conferring and regulating mechanical strength between the surrounding cell envelope structure and the cytoplasmic keratin filament network.

[0135] Expression of genes encoding hair constituent proteins or proteins involved in hair formation ( DNA array ) Change compared to the control / Effect of 7 ppm of the peptide according to the invention after 24 or 48 hours of contact.

[0136] [Table 18]

[0137] Changes in hair constituent proteins or proteins involved in hair formation compared to the control (measured by LC-MS / MS) / Effect of 5 ppm of the peptide according to the present invention.

[0138] [Table 19]

[0139] Conclusion: It was found that the gene expression and / or concentration of some compounds involved in hair itself and hair formation increased after contact with the peptides according to the present invention, as confirmed by DNA-array and LC-MS / MS protein studies.

[0140] The compounds according to the invention therefore appear perfectly suitable for action in the hair field to improve hair strength and growth.

[0141] D) Preparation of Galenic Formulations / Compositions According to the Invention The peptides according to the invention may be formulated with additional cosmetic active ingredients that serve to support and / or complement their activity, either in the form of an ingredient or in the realization of the final cosmetic composition for the consumer, which may be applied to the face, body, neck, scalp, hair, eyelashes or body hair, and may be delivered alone or in a premix, or in any form or medium known to those skilled in the art, in particular in the form of a solution, dispersion, emulsion, paste or powder.

[0142] In cosmetics, the treatment applications may be suggested in particular in the skin care range for the face, body, hair, and make-up care range.

[0143] These ingredients may be of any category depending on their function, the area to which they are applied (body, face, neck, bust, hands, hair, eyelashes, eyebrows, body hair, etc.), the desired end effect and the target consumer, such as antioxidant, anti-wrinkle, moisturizing, nourishing, protecting, smoothing, remodeling, volumizing (lipofilling), complexion brightening, anti-darkening, concealing, anti-glycation, anti-aging, anti-wrinkle, slimming, soothing, muscle relaxant, anti-redness, anti-stretch mark, sun protection, etc.

[0144] The International Cosmetic Ingredient Dictionary & Handbook (19th Edition, 2019), published by the CTFA (Cosmetic and Toiletries Manufacturers Association of America, Washington, D.C.), describes a wide variety of non-limiting cosmetic ingredients commonly used in the skin care industry that are suitable for use as additional ingredients in the compositions of the present invention.

[0145] The active ingredients include at least one compound 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, and peptides, which are known active ingredients used in topical cosmetic or dermopharmaceutical compositions. The peptides are, in particular, N-acetyl-Tyr-Arg-O-hexadecyl ester, Pal-VGVAPG (SEQ ID NO 3), Pal-KTFKS (SEQ ID NO 6), Pal-GHK, Pal-KMO2K, Pal-GQPR (SEQ ID NO 2), Pal-K(P)HG (with proline grafted to lysine), and Pal-KTSKS (SEQ ID NO 7).

[0146] Other particularly useful additional skin care actives are listed in Sederma's trade literature and at www.sederma.com or www.crodarom.com.

[0147] In enhancing the activity on the properties of the epidermis and / or stratum corneum, additional active agents may be selected from the group including: phospholipids, various ceramides, sphingosine, phytosphingosine, glycosphingolipids, cholesterol and its derivatives, sterols (especially canola and soy), fatty acids (especially linoleic acid, palmitic acid, lipoic acid, and thioctic acid), squalane (especially olive), triglycerides (especially coconut oil), lanolin, lanolin alcohol, lanosterol, vitamin D3, tocopherol nicotinate, various oils (especially argan, loquat, lauric acid ... Rose, and baobab), ascorbic acid, N-acetylcysteine ​​and N-acetyl-L-serine, vitamin B3 compounds (niacinamide, nicotinic acid, etc.), panthenol, pseudofilaggrin, arginine, serine, PCA (pyrrolidone carboxylic acid) salt, Centella asiatica leaf extract (titrated with madecassoside and asiaticoside), selected plant extracts (wild yam root, chestnut, cedar bud, and solanum), plankton, and yeast.

[0148] Mention may also be made of the following active agents sold by the company Sederma: Venuceane™ (extract of the fermentation medium of Thermus thermophilus), Moist 24™ (hydroglycolic extract of Imperata cylindrica root), Dermaxyl™ (conjugate of ceramide 2 with Pal-VGVAPG peptide), Senestem™ (extract of cell culture of Plantago lanceolata), Ceramide 2™ (ceramide), Ceramide HO3™ (hydroxyceramide), OptimHyal™. Hyal™ (acetylated glucuronic acid oligosaccharides), Meiritage™ (conjugate of Bupleurum, Astragalus membranaceus and Astragalus maculatus root extracts), Revidrat™ (myristyl phosphomalate), Pacifeel™ (miribana extract), Hydrononesis™ (Salinococcus hispanicus ferment), Shea™ NG unsaponifiables and Citystem™ (horehound cell culture extract).

[0149] The following commercially available active agents may also be mentioned by way of example: betaine, glycerol, Actimoist Bio2™ (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™ (Lipotec's trademark for acetyl hexapeptide-3), spilanthol, or Gatuline Extract of Boswellia serrata known under the trade 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 ingredients sold by Sederma: Subliskin™, Venuceane™, Moist 24™ 24) (trademark), Vegesome Moist 24 (Vegesome Moist24)™, Essenskin™, Juvinity™, Revidrat™, Resistem™, Chronodyn™, Kombucha™, Chromocare™, Calmosensine™, Glycokin factor S™, Biobustyl™, Idealift™, Ceramide 2™, Ceramide A2™, Ceramide HO3 HO3™, Legance™, Intenslim™, Prodizia™, Beautifeye™, Pacifeel™, Zingerslim™, Meiritage™, Senestem™, Sebuless™, Majestem™, Apiscalp™, Rubistem™, Citystem™, Neonyca™, NG Unsaponifiables of Shea Butter Karite™, Majestem™, Hydroonesis™, Poretect™, Crystalide™, Amberstem™, Synchrolife™, and Feminage™, or mixtures thereof.

[0150] Among the plant extracts (in the form of conventional plant extracts or prepared by in vitro treatment) which can be combined with the plant cells of Buddleia tangled according to the invention, there are selected from the group consisting of ivy, in particular English ivy, manchuria, bupleurum, arnica, rosemary, marigold, sage, ginseng, ginkgo, St. John's wort, thuja, meadowsweet, big-flowered Java tea, artichoke, algae, birch, green tea, kola nut, horse chestnut, bamboo, Centella asiatica, heather, fucus, willow, taraxacum, escin, kandu, Chrysanthermum indicum, plants of the genus Armeniacea, atractylodes Extracts of Displatycodon, Sinomenium, Farbitizis, Flemingia, Coleus, such as Coleus forskohlii, Coleus burmei, Coleus esquiroli, Coleus scutellaroides, Coleus xanthos and Coleus barbatus, such as Coleus barbatus root extract, Barotte, Guioa, Davaria), Terminalia, Barringtonia, Trema, Antilobia, Cecropia, Argan, Dioscorea, such as Discorea opposita or Mexican extract, Ammibisnaga, Mentha, especially Mentha equisetum extract, extracts of plants of the Ericaceae family, especially cowberry or bearberry extract, Aloe vera, sterol-containing plants (i.e. phytosterols) ru), Manjistha (extract of plants of the genus Rubia, in particular Rubia cordifolia), and Guggul (extract of plants of the genus Commiphora, in particular Guggul), extract of kola, chamomile, extract of red clover, extract of kava (Kava Kava™, Sederma), extract of Bacopa Monnieri (Bacocalmine™, Sederma), extract of whip goat, extract of Licorice, Mulberry, Melaleuca alternifolia (tea tree), Larrea divaricate, Rabdosia rubescens, Euglena gracilis, Fibraurea recisa hirdinea, extract of Shallot sorghum, extract of Sunflower, Enantia chlorantha, Mitracarpus scapeor, Butuber lomus, Henna L, Capillus capillus L, Celandine, Luffa, Japanese yew Mention may in particular be made of extracts of mandarin, tea plant, Imperata cylindrica, horn poppy, cypress, Solomon's seal, lovely hemlock, elderberry, lima bean, Centaurea japonica, duckweed, Turnella diffusa, flower sedge, portulaca dulcis, hops, coffee plant, yerba mate, Globularia cordifolia, silk tree, sourwood, ginger, Astragalus membranaceus, plantain lanceolata, snowdrop, Mirabilis mirabilis, celery, horehound, Buddleia tulcata, angelica tree, lilac or orchid.

[0151] The compositions of the present invention may include one or more additional peptides, including, but not limited to, di-, tri-, tetra-, penta-, and hexapeptides and derivatives thereof. According to certain embodiments, the concentration of the additional peptide in the composition is greater than or equal to 1×10 -7 % to 20% by weight, and 1×10 -6 The range of 1×10 wt.% to 10 wt.% is preferred. -5The range of % to 5% by weight is preferred. As used herein, the term "peptide" refers to peptides containing 10 or fewer amino acids, their derivatives, isotopes, and complexes with other species, such as metal ions (copper, zinc, manganese, magnesium, etc.). The term "peptides" refers to both natural and synthetic peptides. "Peptides" also refers to compositions containing peptides found in nature and / or commercially available.

[0152] Dipeptides suitable for use in the present invention include, but are not limited to, carnosine (βAH), YR, VW, NF, DF, KT, KC, CK, KP, KK, TT, PA, PM, or PP.

[0153] Tripeptides suitable for use in the present invention include, but are not limited to, RKR, HGG, GKH, GHK, GGH, GHG, KGH, KHG, KFK, KAvaK, KβAK, KAbuK, KAcaK, KPK, KMOK, KMO2K (MO2 is sulfoxide methionine dioxide), KVK, PPL, PPR, SPR, QPA, LPA, SPA, K(Ac)HG, or K(Ac)GH, where K(Ac) is a lysine with an acetylated amine functional group in the side chain, as disclosed in WO 2017 / 216177. As disclosed in WO2016 / 097965, K(P)HG, K(P)GH, or K(P) is a lysine whose side chain is grafted with proline, K(Pyr)HG, K(Pyr)GH, or K(Pyr) is a lysine whose side chain is grafted with pyroglutamic acid, and K(Hyp)HG, K(Hyp)GH, or K(Hyp) is a lysine whose side chain is grafted with hydroxyproline.

[0154] Tetrapeptides suitable for use as additional peptides in the present invention include RSRK (SEQ ID NO:8), GQPR (SEQ ID NO:9), KTFK (SEQ ID NO:10), and TFK (SEQ ID NO:11). No. 10), KTAK (SEQ ID No. 11), KAYK (SEQ ID No. 12), or KFYK (SEQ ID No. 13).

[0155] An example of a suitable pentapeptide is KTSKS (SEQ ID NO:14). Examples of suitable hexapeptides include, but are not limited to, GKTTKS (SEQ ID NO:15), GKTSKS (SEQ ID NO:16), and VGVAPG (SEQ ID NO:17).

[0156] Other peptides suitable for use according to the invention can be selected from the following, but this list is not limiting: lipophilic derivatives of peptides, preferably palmitoyl (Pal) derivatives or myristoyl (Myr), and their metal complexes (e.g., copper complexes of the tripeptide HGG or copper complexes of the tripeptide GHK). Preferred dipeptides include, for example, N-palmitoyl-beta-Ala-His, N-acetyl-Tyr-Arg-hexadecyl ester (Calmosensine™, Idealift™, Sederma), Pal-RT or Pal-KT (Sederma). Preferred tripeptide derivatives include, for example, Pal-GKH and Pal-GHK (Sederma), the copper derivative of HGG (Lamin™, Sigma), lipospondin (N-Elideyl-KFK) and its conservatively substituted analogs, N-acetyl-RKR-NH2 (peptide CK+), N-Biot-GHK (Sederma), Pal-KAvaK, Pal-KβAlaK, Pal-KAbuK, Pal-KAcaK, or Pal-KMO2K (Matrixyl® Synthe' 6®, Sederma), Pal-KVK (Syn-Coll™, DSM), and derivatives thereof.

[0157] Here, the general formula X-Pro * -Pro *Anti-aging tripeptides of -Xaa-Y may also be mentioned, where Xaa is selected from Leu, Arg, Lys, Ala, Ser, and Asp at the N-terminus, and X is H, -CO-R at the C-terminus. 1 and -SO2-R 1 Y is selected from OH, OR 1 , NH2, NHR 1 or NR 1 R 2 Selected from: R 1 and R 2 are each independently selected from linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurized alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy groups, which optionally contain heteroatoms in their backbone, in particular O, S and / or N. * corresponds to proline, its analogs or derivatives; for example, the general formula X-Pro * -Pro * -Xaa-Y includes Myr-PPL-OH and Myr-PPR-OH.

[0158] Further, the general formula X-(Xaa1)n-Pro disclosed in WO2014 / 080376 is * Reference can be made to pigmentation-promoting and / or ECM-promoting dipeptides and tripeptides of -Xaa2-Y. When n=0, 1, or 2, Xaa1 is a hydrophobic amino acid selected from Ala, Val, Met, Leu, Iso, Phe, and Pro, and analogs and derivatives thereof, or a polar amino acid selected from Ser, Thr, Tyr, Asp, and Glu, and analogs and derivatives thereof; when n=2, the two amino acids Xaa1 are the same or different; Xaa2 is a hydrophobic amino acid selected from Ala, Val, Met, Leu, Iso, and Phe, and analogs and derivatives thereof, or a basic amino acid selected from Arg, Lys, and His, and analogs and derivatives thereof; and at the N-terminus, X is H, -CO-R 1 and -SO2-R 1at the C-terminus, Y is selected from OH, OR 1 , NH2, NHR 1 or NR 1 R 2 Selected from; R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy groups, which may be linear, branched, cyclic, polycyclic, saturated, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurized, with or without O, S and / or N heteroatoms in the backbone, and * corresponds to proline, an analogue or a derivative thereof; for example, the general formula X-(Xaa1)n-Pro * -Xaa2-Y is the following peptide Pal-SPR-OH, Pal-PPR-OH, Pal-QPA-OH, Pal-LPAOH, My Includes r-SPA-OH, Pal-PM-OH, Pal-PA-OH and Pal-PP-OH.

[0159] Tetrapeptide derivatives suitable for use as additional peptides according to the present invention include, but are not limited to, Pal-GQPR (SEQ ID NO:2) (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). Pentapeptide derivatives suitable for use as additional peptides herein include, but are not limited to, Pal-KTSKS (SEQ ID NO:7), Pal-YGGFXaa (SEQ ID NO:22) in which Xaa is Leu or Pro, or mixtures thereof.

[0160] Hexapeptide derivatives suitable 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 where Xaa is Trp, Phe, Tyr, Tic, 7-hydroxy-Tic, or Tpi (7-hydroxy-Tic or Tpi) (SEQ ID NO:24), and derivatives thereof. Also included are mixtures of Pal-GHK and Pal-GQPR (SEQ ID NO:2) (Matrixyl® 3000, Sederma).

[0161] Preferred commercially available compositions containing tripeptides or derivatives include Biopeptide-CL™, Maxilip™, Biobustyl™, Procapil™, and Matrixyl® Synthe' 6® from Sederma. Preferred commercially available source compositions of tetrapeptides include Rigin™, Eyelis™, Matrixyl® Reloaded, and Matrixyl 3000® containing between 50 and 500 ppm Pal-GQPR (SEQ ID NO:2), Crystalide™, and excipients offered by Sederma.

[0162] Additional active ingredients may also include the following commercially available peptides: Vialox™ (INCI name = Pentapeptide-3 (synthetic peptide containing alanine, arginine, isoleucine, glycine, and proline)), Syn-Aake™ (β-Ala-Pro-Dab-NH-Bzl) or Syn-Coll™ (Pal-Lys-Val-Lys-OH), sold by Pentapharm; Argireline™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (INCI name = acetyl hexapeptide-3)) (SEQ ID NO: 25), Leuphasyl™ (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID NO: 26), available from Lipotec. NO:26), Aldenine™ (Gly-His-Lys), Trylagen™ (INCI Name = Pseudoalteromonas fermentation extract, wheat protein hydrolysate, soy protein hydrolysate, tripeptide-10 citrulline (reaction product of citrulline and tripeptide-10 (a synthetic peptide consisting 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) The reaction product of citrulline and tripeptide-10 (a synthetic peptide consisting of aspartic acid, isoleucine, and lysine); Collaxyl™ (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID NO: 29)) or Quintescine™ (Cys-Gly), available from Vincience; Cytokinol™ LS (casein hydrolysate), sold by Les Laboratoires Serobiologiques / Cognis; Kollaren™ (Gly-His-Lys), IP2000™ (Pal-Val-Tyr-Val) or Meliprene™ (INCI name = Monofluoroheptapeptide-1: reaction product of acetic acid with a synthetic peptide containing arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan), sold by the European Biological Institute; Neutrazen™ (Pal-His-D-Phe-Arg-NH2), available from Introvations; BONT-L-Peptide™ (INCI name = Palmitoyl Hexapeptide-19: reaction product of palmitic acid with hexapeptide-19, a synthetic peptide consisting of asparagine, aspartic acid, lysine, and methionine), Timp-Peptide™ (INCI name = Acetyl Hexapeptide-20: reaction product obtained by acetylation of hexapeptide-20, a synthetic peptide consisting of alanine, glycine, lysine, valine, and proline), or ECM Moduline™ (INCI name = Palmitoyl Tripeptide-28: reaction product of palmitic acid with tripeptide-28, a synthetic peptide consisting of arginine, lysine, and phenylalanine), sold by Infinitec Activos.

[0163] It is also possible to envisage combining the plant cells according to the invention with one or more cyclic peptides, in particular peptides extracted from linseed oil, as described in the applicant's patent application FR1850845.

[0164] Various compositions / formulations according to the present invention are described below, along with some examples of additional active ingredients.

[0165] The active ingredients according to the invention are as described in section C / and contain 100 ppm of peptide(s) according to the invention as described above.

[0166] This component is generally present at between 1% and 5%, preferably 3%.

[0167] 1) Cream form , e.g., facial anti-aging day cream

[0168] [Table 20]

[0169] Examples of additional active ingredients: 1. Moisturizing / smoothing ingredients such as: OPTIM HYAL™, sold by Sederma, contains oligosaccharides of acetylated glucuronic acid with a structure similar to fragments of hyaluronic acid. 2. Sebum-regulating ingredients such as: SEBULESS™: Sold by Sederma, a sebum-regulating agent containing lilac extract obtained through in vitro cell culture, cleanses, reduces shine, provides a cooling sensation, and reduces the appearance of fine lines. PORETECT™: Sold by Sederma, this product is a blend of flaxseed and celery extracts titrated with cylolinopeptides and senkyunolides, which gives skin firmness, tone, and density, strengthening the pore-holding structure that tends to break down with age. 3. Active strengthening: Ingredients that act on the elastic properties of the skin / skin barrier, such as: IDEALIFT™: Marketed by Sederma, it contains the lipodipeptide N-acetyl-tyrosyl-arginyl-O-hexadecyl ester, which combats facial sagging and improves resistance to gravity by specifically stimulating elastin. DERMAXYL™: Sold by Sederma, this product combines ceramide 2, a stratum corneum binding agent, with Pal-Val-Gly-Val-Ala-Pro-Gly, a palmitoyl-formulated matrikine, to smooth wrinkles and repair the skin barrier.

[0170] 2) A mild, water-based serum

[0171] [Table 21]

[0172] Examples of additional ingredients : 4. Anti-aging ingredients such as: SENESTEM™, marketed by Sederma, contains plant cells obtained by in vitro cell culture of Plantago lanceolata, and is particularly effective in improving the viscoelastic properties of the skin and lightening age spots. 5. Antioxidants such as: MAJESTEM™, sold by Sederma and based on plant cells of the snowdrop plant obtained in vitro in a cell culture, titrated with leontopodic acid; neutralizes oxidative stress (pollution, UV radiation) and restores skin firmness.

[0173] 3) Gel form

[0174] [Table 22]

[0175] Examples of additional active ingredients: 6. "Anti-pollution" ingredients such as: Citystem™, marketed by Sederma and based on plant cells obtained in vitro from horehounds with a high concentration of Forsythoside B; used against pollution attacks. Skin becomes softer and smoother, the texture is refined, the visibility of comedones is reduced, and the skin is brightened and purified. 7. Soothing ingredients for sensitive skin such as: Pacifeel™, sold by Sederma, contains extract of Mirabilis mirabilis. 8. Moisturizing ingredients such as: AQUALANCE™, sold by Sederma, is an osmoprotective moisturizing active ingredient consisting of homarine and erythritol.

[0176] 4) Gel form to realize spray mask

[0177] [Table 23]

[0178] Examples of additional active ingredients: 9. Ingredients that work on complexion radiance, such as: EVERMAT™: Sold by Sederma, contains a combination of protoberberine-rich Enantia chlorantha extract and oleic acid; reduces pore size and shine; refines acne-prone skin texture. 10. Ingredients with activating properties such as: Fruitliquid™ Kumquat™, sold by Crodarom.

[0179] 5) Cream form , for makeup base

[0180] [Table 24]

[0181] Examples of additional active ingredients: 11. Concealer / eye contour ingredients such as: HALOXYL™, sold by Sederma, contains two matrikines, Pal-GHK and Pal-GQPR, plus N-hydroxysuccinimide and a flavonoid. Contains chrysin, a EYELISS™, sold by Sederma, contains three ingredients: hesperidin methyl chalcone, the dipeptide valyltryptophan (VW), and the lipopeptide Pal-GQPR. PRODIZIA™, from Sederma, contains extract of the silk tree, which repairs and protects the skin from the damage caused by glycation, thereby reducing the visible signs of fatigue, such as dark circles, bags under the eyes, dullness, paleness, and a tense complexion. 12. Anti-wrinkle / anti-aging ingredients based on peptide(s), such as: MATRIXYL 3000™, MATRIXYL Synthe' 6™ and / or MATRIXYL Morphomix, available from Sederma. Morphomics)(trademark).

Claims

1. Use of at least one peptide of general formula 1 below for the non-therapeutic cosmetic treatment of the keratinous tissue of the skin and its appendages, X-(Xaa)nK * TTK * X'aa-(Xaa)m-Z... Formula 1 In the general formula 1: ・K * is selected from lysine, hydroxylysine, ornithine, diaminobutyric acid, or diaminopropionic acid, or a formylated, acetylated, trifluoroacetylated, methanesulfonylated, or succinylated derivative thereof, and both K * are the same or different; (Xaa)n and (Xaa)m correspond independently to a sequence of n or m amino acids Xaa, independently selected from Gly, Ala, Pro, Val, Leu, He, and Phe, where n and m are integers between 0 and 5, which may be equal or different; X'aa is selected from threonine and serine; The N-terminal X is H, -CO-R 1 , -SO 2 -R 1 or a biotinoyl group; ・C-terminal Z is OH, OR 1 , N.H. 2 , N.H.R. 1 , or NR 1 R 2 Selected from: ・R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfurized, said groups having 1 to 24 carbon atoms and optionally containing one or more O, S, and / or N heteroatoms in their backbone; use.

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

3. The treatment is adapted to protect the skin and its appendages from external environmental molecules and aggressors, including protection against bacteria, inflammation, and radiation.

3. Use according to claim 1 or 2.

4. The treatment is adapted to improve hydration of the upper epidermis by reducing transepidermal water loss (TEWL), Use according to any one of the preceding claims.

5. The treatment is adapted to treat epidermal scars, Use according to any one of the preceding claims.

6. The treatment is adapted to treat epidermal acne scars, Use according to any one of the preceding claims.

7. The treatment is adapted to beautify nails, hair, and body hair (including eyelashes and eyebrows), 3. Use according to claim 1 or 2.

8. the treatment is adapted to combat acne and / or dandruff microorganisms, 4. The use according to claim 3.

9. The at least one peptide is used in vectorized form by being bound, incorporated or absorbed in macro-, micro- or nano-particles such as capsules, spheres, liposomes, oleosomes, chylomicrons, sponges, in the form of micro- or nanoemulsions, or by being adsorbed on, for example, powdered organic polymers, talc, bentonite, spores or exines, and other inorganic or organic supports, Use according to any one of the preceding claims.

10. Use of at least one peptide having the following general formula 1 for the preparation of a composition for the treatment of the keratinous tissue of the skin and its appendages, X-(Xaa)nK * TTK * X'aa-(Xaa)m-Z... Formula 1 In the general formula 1: ・K * is selected from lysine, hydroxylysine, ornithine, diaminobutyric acid, or diaminopropionic acid, or a formylated, acetylated, trifluoroacetylated, methanesulfonylated, or succinylated derivative thereof, and both K * are the same or different; (Xaa)n and (Xaa)m correspond independently to a sequence of n or m amino acids Xaa, independently selected from Gly, Ala, Pro, Val, Leu, He, and Phe, where n and m are integers between 0 and 5, which may be equal or different; X'aa is selected from threonine and serine; The N-terminal X is H, -CO-R 1 , -SO 2 -R 1 or a biotinoyl group; ・C-terminal Z is OH, OR 1 , N.H. 2 , N.H.R. 1 , or NR 1 R 2 Selected from: ・R 1 and R 2 are independently selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfurized, said groups having 1 to 24 carbon atoms and optionally containing one or more O, S, and / or N heteroatoms in their backbone; use.

11. K * is lysine or ornithine; Use according to any one of the preceding claims.

12. X'aa is serine; Use according to any one of the preceding claims.

13. n and m are independently 0, 1, or 2; Use according to any one of the preceding claims.

14. the peptide is modified at either the N-terminal or C-terminal position; Use according to any one of the preceding claims.

15. R 1 and / or R 2 is an alkyl chain of 1 to 24 carbon atoms; Use according to any one of the preceding claims.

16. R 1 and / or R 2 is an alkyl chain of 3 to 24 carbon atoms; Use according to any one of the preceding claims.

17. X is CO-R 1 and Z is OH, OMe, OEt, and NH 2 Choose from To be selected, Use according to any one of the preceding claims.

18. The peptide is Pal-KTTKS (SEQ ID NO 1), Use according to any one of the preceding claims.

19. 1. A method of treating skin comprising topically applying to skin in need thereof an effective amount of the peptide of the above claims, the treatment is antimicrobial (antibacterial or antifungal) and / or anti-inflammatory; The treatment is particularly suitable for soothing sensitive and irritated skin and / or for treating acne, psoriasis, dermatitis and eczema. Skin treatment methods.

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