Peptide-based hair treatment

Abstract

The treatment according to the invention involves the use of at least one peptide of general formula X-(Xaa)nGQPR(Xaa)m-Z for a non-therapeutic cosmetic hair treatment. In the formula, Xaa is an amino acid chosen from proline (P, Pro), glycine (G, Gly), alanine (A, Ala), valine (V, Val), leucine (L, Leu) and isoleucine (I, Ile), the Xaa being chosen independently of each other; with n and m integers which may be identical or different and being comprised between 0 and 5; at the N-terminus X is chosen from H, CO-R1 or SO2-R1; at the C-terminus Z is chosen from OH, OR1, NH2, NHR1 or NR1R2; R1 and R2 being, independently of each other, chosen from an alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurated, said group containing from 1 to 24 carbon atoms and possibly having in its backbone one or more heteroatoms O, S and / or N. Preferred peptide sequences are Pal-GQPR-OH or Pal-GQPR-NH2. These peptides act at several levels: hair follicle stem cells, dermal papillae, signalling pathways, and the extracellular matrix. They may be used for cosmetic hair treatment in particular for protecting the structure of head hair and / or bodily hair, including eyelashes and eyebrows, slowing down their loss, inducing and / or stimulating their growth, preventing their depigmentation and / or inducing their pigmentation.

Description

Peptide-based hair treatment

[0001] The present invention relates to a peptide-based hair treatment, i.e. both head hair (the hair) and bodily hair (including eyelashes and eyebrows), of mammals, animals or humans.

[0002] In the context of the present invention, the term "peptide" denotes here peptides containing twenty or fewer amino acids, derivatives thereof, isomers and complexes with other species such as a metal ion (for example: copper, zinc, manganese, magnesium, and others). The term "peptides" refers to both natural peptides and (bio)synthesized peptides. It also refers to peptide-containing compositions that occur in nature and / or that are commercially available.

[0003] The present invention relates to the cosmetics, hygiene products, personal care and dermopharmacy industries, for both humans and animals.

[0004] More particularly, the present invention relates to a means for inducing and / or stimulating the growth of head hair, bodily hair, the eyelashes and the eyebrows, protecting their structure, slowing down their loss, preventing their depigmentation and / or inducing their pigmentation.

[0005] Head hair and bodily hair comprise two parts, the hair follicle and the hair shaft, and also ancillary structures, the most important of which are the sebaceous gland, which plays a lubricating role, and the arrector muscle, which erects the hair to regulate temperature or help excrete sebum.

[0006] To simplify the following description, the terms "head hair" or "bodily hair" will be used interchangeably to encompass "head hair, bodily hair, eyelashes and eyebrows".

[0007] The hair follicle is the non-visible part of the skin. It is divided into three segments, from top (epidermis) to bottom (dermis):

[0008] - The infundibulum extends from the epidermal surface to the sebaceous gland.

[0009] - The isthmus is located in the dermis, between the sebaceous gland and the insertion site of the arrector muscle. This insertion site, also known as the bulge, is a stem cell niche.

[0010] - The bulb is located in the dermis, below the bulge. At the base of the bulb is the papillary dermis, made up of mesenchymal cells called HFDPCs (Human Follicle Dermal Papilla Cells), which interact with the other bulb cells to induce hair growth. The papillary dermis also contains blood vessels which supply the nutrients and oxygen needed for growth of the hair shaft or fibre. Above and around the dermal papilla is a "germinative" zone containing stem cells (keratinocytes, melanocytes and matrix cells). The keratinocytes of the germinative zone are pigmented by neighbouring melanocytes. These keratinocytes enter a phase of differentiation and apical migration, giving rise to the keratogenic zone in which keratin is produced. The matrix cells proliferate and differentiate, giving rise to the shaft.

[0011] The hair shaft or fibre is the visible part that is outside the hair follicle. It is made up of three layers, from the outside inwards:

[0012] - The cuticle is made up of cells arranged in scales, allowing hair to be protected from external attacking factors.

[0013] - The cortex is composed of fibrous, fusiform cortical cells, sealed and embedded in each other. The cortex gives the hair colour, strength and resistance.

[0014] - The marrow is made up of medullary cells, which are degenerated and replaced by large vacuoles filled with air and a few melanin grains.

[0015] Head hair and bodily hairs are essential for protecting the skin and scalp from external aggressions. They are made up mainly of keratin.

[0016] Their growth and renewal are mostly determined by the activity of the hair follicles and their matrix environment. Their activity is cyclical and essentially includes three phases: the anagen phase, the catagen phase and the telogen phase, which are repeated until the hair dies. Thus, hair does not grow continuously, but in successive cycles. This cycle repeats itself between twenty-five and thirty times over the course of a lifetime, by virtue of the regenerative ability of the follicle stem cells that reside in the bulb region.

[0017] The hair cycle begins with the anagen phase, corresponding to strong hair growth inside the hair follicle. On average, this phase lasts from 2 to 5 years. 85% to 90% of hair is usually in the anagen phase. During this phase, the hair bulb regenerates and then produces the hair fibre. Hair thus grows at about 1 cm per month. This highly proliferative phase results from the proximity between the dermal papilla, in contact with blood vessels, and the "bulge" in which the hair stem cells are located. From there, by virtue of the intense production of keratin and keratinocytes, the fibre is manufactured, forming the hair's external cuticles and cortex.

[0018] At the end of this anagen phase, the follicle enters a regression phase called the catagen phase, and synthesis stops. The fibre no longer grows, due to a lack of feed for the dermal papilla via the blood vessels. This phase only lasts a few weeks, and concerns about 2-3% of the hair at any given instant. The follicle gradually retracts and involutes. The keratinocytes and melanocytes slowly disappear, and the bulb collapses in on itself, while maintaining the dermal papilla.

[0019] Next, the dermal papilla begins to rise towards the bulge. This is the telogen phase, preceding a new anagen phase. 8% to 10% of the hair is in the telogen phase at a given instant. It remains in this phase for about 6 to 7 months in young people, but for longer with increasing age.

[0020] This hair cycle is the same for bodily hair, with different phase durations and different cycles, especially the duration of the anagen phase is shorter for bodily hair.

[0021] Head hair is generally damaged and weakened by the action of external atmospheric agents such as light and bad weather, and also by mechanical or chemical treatments such as brushing, combing, dyeing, bleaching, perming and / or straightening, or even repeated washing.

[0022] In addition, as hair ages, it becomes thinner, and the cycles become shorter.

[0023] The hair is thus damaged and may become dry, rough, brittle, dull or result in hair loss, reducing the hair density.

[0024] To overcome these drawbacks, it is common practice to use products intended for hair or scalp treatment, such as plant extracts, pure synthetic molecules, vitamins and keratin hydrolysates with various sulphur compounds.

[0025] There is thus still a need for effective products that reduce side effects such as the risk of irritation and allergy, to preserve and / or improve the general condition of head hair or bodily hair.

[0026] In response to this problem, the present invention provides the use of a peptide for a cosmetic hair treatment.

[0027] To this end, according to a first subject, the present invention provides the use of at least one peptide of general formula X-(Xaa)nGQPR(Xaa)m-Z(SEQ ID NO: 1), in which:

[0028] - Xaa is an amino acid chosen from proline (P, Pro), glycine (G, Gly), alanine (A, Ala), valine (V, Val), leucine (L, Leu) and isoleucine (I, Ile), the Xaa being chosen independently of each other, with n and m being integers which may be identical or different comprised between 0 and 5;

[0029] - at the N-terminus X is chosen from H, CO-R1or SO2-R1;

[0030] - at the C-terminus Z is chosen from OH, OR1, NH2, NHR1or NR1R2;

[0031] - R1and R2being, independently of each other, chosen from an alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurated, said group containing from 1 to 24 carbon atoms and possibly having in its backbone one or more heteroatoms O, S and / or N;

[0032] for a non-therapeutic cosmetic hair treatment.

[0033] The term "non-therapeutic cosmetic treatment" means a treatment intended for head hair and / or bodily hair being in a healthy state (as opposed to a pathological state), with the aim of beautifying it or preventing (as a preventive measure) aesthetic disorders, for example sparse hair.

[0034] According to the invention, the Xaa may be identical or different. Preferably, the Xaa are chosen from glycine (G, Gly) and alanine (A, Ala).

[0035] The Pal-GQPR (SEQ ID NO: 2) is used in several cosmetic active agents sold by Sederma. For example, in the RIGIN™ product as an anti-ageing cosmetic active agent for improving skin quality, in the Matrixyl 3000™ product in combination with Pal-GHK as an anti-ageing cosmetic active agent, in the Haloxyl™ product in combination with Pal-GHK, N-hydroxysuccinimide and chrysin as an active agent for combating eye shadows, or in the Synchrolife™ product in combination with chrysin and rosemary extract as an active agent for combating signs of skin fatigue.

[0036] The inventors have shown, surprisingly, that the peptide according to the invention is particularly advantageous for significantly improving the stimulation of growth of head hair, bodily hair, including eyelashes and eyebrows, and / or for slowing down their loss, preventing their depigmentation and / or inducing their pigmentation.

[0037] According to a preferred feature, the peptide according to the invention is modified at its N-terminus and / or C-terminus. Preferably, it is modified only at its N-terminus. Derivatization of the peptide in the N- and / or C-terminal position aims in particular to improve the peptide's bioavailability, by enhancing its penetration into the skin or the scalp. This effect may also be obtained by means of vectorization, for exampleviaencapsulation.

[0038] According to another preferred feature, R1and / or R2is an alkyl chain of 1 to 24 carbon atoms, preferably a lipophilic alkyl chain of 3 to 24 carbon atoms, more preferably 6 to 24 carbon atoms.

[0039] According to another preferred feature, X is an acyl group CO-R1. Preferably, X is chosen from octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl and lipoyl. More preferably, X is chosen from lauroyl (C12), myristoyl (C14) and palmitoyl (C16). More preferably, X is chosen from palmitoyl (C16), myristoyl (C14) and lauroyl (C12). Preferably, X is palmitoyl (C16).

[0040] According to another preferred feature, Z is chosen from OH, OMe, OEt and NH2.Preferably, Z is chosen from OH and NH2.

[0041] Peptides comprising N- or C-terminal derivatives of particular acids such those of as ascorbic, retinoic, cinnamic, oleanolic, hyaluronic, nicotinic, lipoic, gallic or pantothenic acid are also covered by the present invention.

[0042] Particularly preferred peptides according to the invention are Pal-GQPR-OH (SEQ ID NO: 2) and Pal-GQPR-NH2(SEQ ID NO: 3).

[0043] The peptides according to the invention may be optically pure or consist of the L or D isomers or a mixture thereof. The L isomers, which are those present in the natural state, may be preferred.

[0044] The present invention also covers derivatives (with modification and / or addition of a chemical function to one or more of the amino acids but without a change in the carbon backbone) and analogues (with modification and / or addition of a chemical function to one or more of the amino acids but additionally with a change in the carbon backbone), complexes with other species such as a metal ion (for example copper, zinc, manganese, magnesium, and others).

[0045] Where appropriate, the peptides may be in the form of salts, in particular hydrochloric or acetate salts.

[0046] More particularly, the present invention provides a cosmetic hair treatment suitable for:

[0047] - protecting the structure of head hair and / or bodily hair, including eyelashes and eyebrows;

[0048] - slowing down the loss of head hair and / or bodily hair, including eyelashes and eyebrows;

[0049] - inducing and / or stimulating the growth of head hair and / or bodily hair, including eyelashes and eyebrows; and / or

[0050] - preventing depigmentation and / or inducing pigmentation of head hair and / or bodily hair, including eyelashes and eyebrows.

[0051] Specifically, it has been shown that the cosmetic treatment according to the present invention is capable of acting on several levels.

[0052] At the level of the stem cells of thehair follicle, collagen XVII is an important molecule that allows HFSCs (Hair Follicle Stem Cells) to retain their stem cell character. HFSCs are slow-cycling cells that have the ability to induce head hair or bodily hair growth. When collagen XVII is degraded by elastase, the niche of HFSCs is impaired, as is their ability to induce head hair or bodily hair growth. Thus, by protecting collagen XVII from elastase, hair follicle stem cells are protected and the ability to grow and regenerate head hair and / or bodily hair is maintained.

[0053] At the level ofthe dermal papillaecontaining the HFDPCs which aggregate and form a spherical structure. This structure of HFDPCs is necessary for the development of hair follicles, as their dispersion prevents the formation of hair follicles. HFDPCs are also capable of sending signals to hair stem cells to activate their growth. Furthermore, dermal papilla size has an effect on hair thickness. Thus, hair growth and morphogenesis are stimulated by protecting dermal papillae..

[0054] At the level ofthe signalling pathwaysERK (or Extracellular signal-regulated kinases, which add phosphate groups to other proteins to activate them) and AKT (or protein kinase B, an essential protein in mammalian cell signalling). These pathways are involved in cell proliferation, differentiation and apoptosis for ERK, and cell proliferation, migration and aggregation for AKT. Activation of these two pathways thus allows dermal papillae to grow. It is the phosphorylation of ERK and AKT proteins (known as pERK and pAKT) which causes activation of the corresponding signalling pathways. Thus, stimulating phosphorylation of ERK and AKT proteins allows division of the dermal papilla cells responsible for hair growth and morphogenesis.

[0055] At the level ofthe extracellular matrix (ECM), reduced synthesis of extracellular matrix proteins such as collagen, laminins and fibronectin, for example, leads to a loss of dermal elasticity and tone. There is also a reduction in the coherence and organizing of hair follicles, a decrease in their anchorage, a reduction in the duration of the anagen phase and a lengthening of the duration of the telogen phase. The hair is thinner and therefore more fragile. The result is reduced hair density and a gradual reduction in follicle diameter, giving the head hair a poorer, sparser appearance.

[0056] Hyaluronic acid is also found in the extracellular matrix. Hyaluronic acid is a single-repeat disaccharide polymer found mainly in the dermis and the epidermis.

[0057] This molecule has the ability to absorb 1000 times its weight in water. It plays a role in skin moisturization and in the prevention of skin and hair ageing. Hyaluronic acid contributes to keratinocyte activity, including cell adhesion and proliferation, and interacts with numerous molecules such as cytokines, growth factors, chemokines and cell receptors. For example, CD44 is a hyaluronic acid receptor present on the cell surface. CD44 is involved in cell-cell interactions and cell adhesion.

[0058] A reduction in hyaluronic acid and / or CD44 is accompanied by a reduction in cell proliferation, survival and motility. By binding to CD44, hyaluronic acid entails phosphorylation of the AKT protein, and thus activation of the corresponding metabolic pathway to promote hair growth and morphogenesis. Thus, stimulating the synthesis of hyaluronic acid and of the proteins contained in the extracellular matrix allows better anchoring and growth of the follicle, head hair and / or bodily hair, reducing their loss and preserving and / or improving their general condition.

[0059] At the gene level, HAPLN1 (Hyaluronan and Proteoglycan Link Protein 1), a glycoprotein, is known for maintaining the integrity of the extracellular matrix and for its ability to combat hair loss. It is predominantly expressed in the anagen phase of the hair cycle. HAPLN1 allows hair matrix cells to proliferate and inhibits hyaluronic acid degradation. Thus, an increase in HAPLN1 gene expression prevents hyaluronic acid degradation, combats hair loss and increases the proliferation of hair matrix cells.

[0060] It is also known that human recombinant HAPLN1 (rhHAPLN1) activates the ERK signalling pathway induced by the TGF-β2 gene. Thus, an increase in the TGF-β2 gene increases ERK phosphorylation and activates the corresponding pathway, allowing division of the dermal papilla cells responsible for hair growth and morphogenesis. Thus, an increase in the TGF-β2 gene allows better hair growth and morphogenesis.

[0061] At the level ofmelanocytes, reduced activity of tyrosinase (an enzyme having an intermediate role in melanin formation) and melanin synthesis lead to hair whitening. Thus, stimulating melanin synthesis and tyrosinase activity allows head hair and / or bodily hair greying to be avoided.

[0062] Results ofin vitrotests are given below in the description to demonstrate these specific cosmetic activities, beneficial for head hair and bodily hair. The detailed description also presents anex vivostudy on the growth of bodily hair fibre and / or head hair fibre from hair follicles obtained from facelift surgeries.

[0063] Visually, this is reflected by an improvement in the overall condition of the head hair and / or bodily hair. Thus, the treatment according to the invention prevents hair from being dry, rough, brittle, dull and / or to present split ends.

[0064] According to a second subject, the present invention also provides the use of a composition, in particular a topical composition, comprising at least one peptide according to the invention and a physiologically acceptable medium.

[0065] The term "topical treatment" or "topical use" means an application that is intended to act where it is applied.

[0066] According to the present invention, the term "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.

[0067] The term "physiologically acceptable" means that the composition is suitable for topical use in contact with mucous membranes, the nails, the scalp, head hair, bodily hair, including the eyelashes and the eyebrows, and mammalian and more particularly human skin, without any risk of toxicity, incompatibility, instability, allergic response, and others.

[0068] This "physiologically acceptable medium" is conventionally referred to as the composition's excipient.

[0069] Depending on the physiologically acceptable medium and the concentration of peptide(s), this composition may constitute a concentrated active ingredient intended for entering in a final consumer composition, or may directly constitute said final composition, less concentrated.

[0070] In a composition according to the invention, the peptide(s) may be present at a higher or lower concentration depending on its intended use, ranging from 10-7% to 20% relative to the total weight of the composition, preferably ranging from 10-6% to 10%, more preferentially from 10-5% to 5%, by weight relative to the total weight of the composition.

[0071] For example, in a composition forming an ingredient according to the invention, at least one peptide according to the invention will be present at a high concentration generally ranging from 100 ppm to 20 000 ppm, preferably ranging from 100 ppm to 5000 ppm, more preferably from 100 ppm to 1000 ppm. This ingredient will then be formulated generally between 0.01% and 10%, preferably between 1% and 5% in the final topical preparation.

[0072] When several peptides according to the invention are present in a composition according to the invention, they may be present in variable relative proportions, in equivalent amounts, or on the contrary in different proportions.

[0073] All the percentages and ratios used in the present patent application are expressed relative to the weight of the total composition and all measurements are taken at 25°C unless otherwise specified.

[0074] According to a particular aspect of the invention, the peptide(s) may be dissolved in a lipophilic or hydrophilic matrix, where appropriate with a solubilizer, depending on the intended application.

[0075] The peptide(s) in the treatment according to the invention can be combined with other active ingredients at effective concentrations that can act synergistically or as reinforcement to achieve the desired effects described for the invention, such as the following agents: soothing, moisturizing, antioxidizing, combating hair loss, anti-dandruff, restoring skin flora, acting on cuticles, on the softness and silky appearance of head hair and bodily hair, etc. These active ingredients may be obtained from plant materials, such as plant extracts or products ofin vitroplant culture or fermentation.

[0076] The peptide according to the invention can be combined with one or more other active ingredients at effective concentrations that can act synergistically or as reinforcement to achieve the desired effects described for the invention, such as the following agents: for screening out radiation, in particular UVA, UVB, IR, from blue light, moisturizing, soothing, muscle-relaxing, restructuring, acting on the microcirculation, acting on the cutaneous microbiome, acting on inflammation, on free-radicals, vitamins, anti-wrinkle, etc.

[0077] More particularly, to improve or beautify the general condition of head hair and / or bodily hair, the peptide according to the invention may be combined, without this list being exhaustive, with one or more active agents:

[0078] - an anti-dandruff active agent acting as an antifungal agent: such as Zinc Pyrithione, Ketoconazole, Climbazole, Piroctone Olamine, Selenium Disulfide, Pycnidione, or also APISCALPTM, Matrixyl® or BB-Biont™, Applicant's active agents; and / or

[0079] - an active agent which slows down or inhibits the growth of yeasts responsible for dandruff (of the Malassezia genus) and acting favourably on the skin barrier, such as the peptide Pal-KTTKS (SEQ ID NO: 4) or Pal-KTSKS (SEQ ID NO: 5); and / or

[0080] - a moisturizing active agent such as DuraQuench IQTM(CRODA) or INSAPONIFIABLE de KARITE (Sederma); and / or

[0081] - an active agent that rebalances skin microflora, such as HAIRSPATM(SEDERMA);

[0082] - a soothing active agent such as PACIFEELTM(SEDERMA); and / or

[0083] - an active agent for preventing hair loss and stimulating hair growth, such as CAPIGENETM, CAPILECTINETM, PROCAPILTM(SEDERMA); and / or

[0084] - an active agent for reinforcing the structure of damaged hair, such as CERAMIDE A2TM, CERAMIDE HO3TM, HELIOGENOLTM(SEDERMA); and / or

[0085] - an active agent for smoothing out hair, such as FRUIT BIOTM(SEDERMA); and / or

[0086] - an active agent for protecting head hair and bodily hair, including the eyelashes and the eyebrows, against UV and IR radiation, such as VENUCEANETM; and / or

[0087] - an agent for repigmenting head hair and bodily hair, including the eyelashes and the eyebrows, such as SYLVERFREETM.

[0088] Detailed examples are given in the formulation section below.

[0089] The Personal Care Products Council ("International Cosmetic Ingredient Dictionary & Handbook" published by "The Cosmetic, Toiletry and Fragrance Association, Inc.", Washington, D.C.) describes a wide variety, without limitation, of cosmetic and pharmaceutical ingredients commonly used in the care industry, which are suitable for use as additional ingredients in the compositions according to the present invention, as long as they are physically and chemically compatible with the other ingredients of the composition and especially with the active agents of the present invention. Moreover, the nature of these additional ingredients must not impair the benefits of the active agents of the invention. These additional ingredients may be synthetic or natural, for instance plant extracts, or derived from a biofermentation process.

[0090] Other active agents for skincare, including scalp care, which are particularly useful in combination with the composition according to the invention can be found in the sales literature from Sederma, Crodarom and Alban Muller International, and at www.crodabeauty.com.

[0091] By way of example, the following commercial active agents may also be mentioned: betaine, 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™ (trade name of Lipotec's acetyl hexapeptide-3), spilanthol or an extract ofAcmella oleraceaknown under the name Gatuline Expression™, an extract ofBoswellia serrataknown 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(s) sold by Sederma: Subliskin™, Venuceane™, Moist 24™, Vegesome Moist 24™, Essenskin™, Juvinity™, Revidrat™, Resistem™, Chronodyn™, Kombuchka™, Chromocare™, Calmosensine™, Glycokin Factor S™, Biobustyl™, Idealift™, Ceramide 2™, Ceramide A2™, Ceramide HO3™, Legance™, Intenslim™, Prodizia™, Beautifeye™, PacifeelTM, Zingerslim™, Meiritage™, Sebuless™, Apiscalp™, Rubistem™, CitystemTM, NeonycaTM, NG Shea Butter UnsaponifiablesTM, MajestemTM, HydronesisTM, PoretectTM, AmberstemTM, Synchrolife™, FeminageTM, SylverfreeTM, AmeyezingTM, RevitalideTM, Mel[o]stemTM, LuceaneTMor mixtures thereof.

[0092] Among the plant extracts (in the form of conventional extracts or those prepared byin vitro methods) which may be used as additional active agents, mention may also be made, in particular, of extracts of ivy, for example climbing ivy (Hedera helix),Bupleurum chinensis,Bupleurumfalcatum, arnica (ArnicamontanaL.), rosemary (Rosmarinus officinalisN.), calendula (Calendula officinalis), sage (Salvia officinalisL.), ginseng (Panax ginseng),Ginkgo biloba, St. John's wort (Hypericum perforatum), butcher's broom (RuscusaculeatusL.), meadowsweet (FilipendulaulmariaL.), orthosiphon (OrthosiphonstamincusBenth.), artichoke (Cynara scolymus), seaweed (Fucusvesiculosus), birch (Betula alba), green tea, cola nut (Cola nitida), horse chestnut, bamboo,Centellaasiatica, heather, rockweed, willow, pilosella, extracts of escin, extracts of cangzhu, extracts ofChrysanthellumindicum, plants of theArmeniaceagenus,Atractylodisplaticodon,Sinnomenum,pharbitidis,Flemingia,Coleussuch asC.forskohlii,C.blumei, C.esquirolii, C.scutellaroides, C.xanthantusandC. barbatus, such as an extract ofColeus barbatusroots, extracts of Ballote, Guioa,Davallia,Terminalia,Barringtonia, Trema,Antirobia, Cecropia, Argania,Dioscoreaesuch asDioscoreaoppositaormexicana, extracts ofAmmivisnaga,Siegesbeckia, in particularSiegesbeckiaorientalis, plant extracts of theEricaceaefamily, in particular extracts of bilberry (Vaccinium angustifolium), Arctostaphylos uvaursi,Aloe vera, sterol-containing plants (in particular phytosterols),Manjistha(extract of plants of theRubiagenus), in particularRubia cordifolia), Guggal (extract of plants of the genusCommiphora, in particularCommiphoramukul), an extract of kola, chamomile, red clover,Pipermethysticum(Kava Kava from Sederma),Bacopamonnieri(Bacocalmine™, Sederma) and sea whip,Glycyrrhiza glabra, mulberry, melaleuca (tea tree),Larreadivaricata,Rabdosiarubescens,Euglenagracilis,Fibraurearecisahirudinea,Chaparral sorghum, sunflower,Enantiachlorantha, Mitracarpe of theSpermacoceagenus,Buchubarosma,LawsoniainermisL.,Adiantiumcapillus-venerisL.,Chelidonium majus,Luffa cylindrica, Japanese Mandarin (Citrus reticulatablanco var. unshiu),Camelia sinensis,Imperata cylindrica,Glauciumflavum,Cupressus sempervirens,Polygonatummultiflorum,Lovelyhemsleya,Sambucus nigra,Phaseolus lunatus, Centaurium,Macrocystispyrifera,Turneradiffusa,Anemarrhenaasphodeloides,Portulacapilosa,Humuluslupulus,Coffea arabica,Ilexparaguariensis,Globularia cordifolia,Oxydendronarboreum,Albizziajulibrissin,Zingiber zerumbetsmith,Astragalusmembranaceus,Atractylodesmacrocephalae,Plantago lanceolata,Leontopodium alpinum(or eldelweiss),Mirabilisjalapa,Apium graveolens,Marrubium vulgare,Buddleja davidiiFranch.,Syringa vulgaris,Engelhardiachrysolepsis,Monarda didyma, or orchids.

[0093] The compositions according to the present invention may comprise peptides, including, but not limited to, di-, tri-, tetra-, penta- and hexapeptides and repetitions and derivatives thereof. According to a particular embodiment, the concentration of the additional peptide, in the composition, ranges between 10-7% and 20%, preferably between 10-6% and 10%, preferentially between 10-5% and 5%, by weight.

[0094] Non-limiting examples of dipeptides that may be used in the context of the present invention include Carnosine (β-AH), YR, VW, NF, DF, KT, KC, CK, KP, KK, TT, PA, PM or PP.

[0095] Non-limiting examples of tripeptides comprise RKR, HGG, GHK, GKH, GGH, GHG, KFK, KAvaK, KβAK, KAbuK, KAcaK, KPK, KMOK, KMO2K, PPL, PPR, SPR, QPA, LPA or SPA. Mention may also be made of non-limiting examples of tripeptides containing:

[0096] - a proline grafted to a lysine such as K(P)HG or K(P)GH; or

[0097] - a proglutamic acid grafted to a lysine such as K(Pyr)HG or K(Pyr)GH; or

[0098] - an acetylated lysine such as K(Ac)HG or K(Ac)GH.

[0099] Non-limiting examples of tetrapeptides are KTFK (SEQ ID NO: 6), RSRK (SEQ ID NO: 7), KTAK (SEQ ID NO: 8), KAYK (SEQ ID NO: 9), KFYK (SEQ ID NO: 10), TKPR (SEQ ID NO: 11), AVPG (SEQ ID NO: 12), VPGA (SEQ ID NO: 13), LKLE (SEQ ID NO: 14), ELED (SEQ ID NO: 15) or LLAN (SEQ ID NO: 16).

[0100] Non-limiting examples of pentapeptides are KTTKS (SEQ ID NO: 17) and KTSKS (SEQ ID NO: 18), and examples of hexapeptides are GKTTKS (SEQ ID NO: 19) and VGVAPG (SEQ ID NO: 20).

[0101] Other peptides that may be used in the context of the present invention can be chosen, without this list being limiting, from: lipophilic peptide derivatives, preferably oleoyl, palmitoyl and myristoyl derivatives, and complexes with the metal ions mentioned above (for example: copper complex of the HGG tripeptide).

[0102] Preferred dipeptides include, for example, N-Palmitoyl-β-Ala-His, N-Acetyl-Tyr-Arg-hexadecyl ester (Calmosensine™, Idealift™, Sederma), Pal-KT, Pal-RT, Pal-PP and Pal-PA (Sederma).

[0103] Preferred tripeptides in particular comprise the copper derivative of HGG (Lamin™, Sigma), Pal-GHK and Pal-GKH (Sederma), lipospondin (N-Elaidoyl-KFK) and its conservative substitution analogues, N-Acetyl-RKR-NH2(Peptide CK+), Pal-KavaK, Pal-KβAlaK, Pal-KAbuK, Pal-KAcaK, Pal-KMO2K (Matrixyl®synthe'6®, Sederma), Pal-KVK (Syn-CollTM,DSM), N-Biot-GHK (Sederma) and derivatives thereof.

[0104] Mention may also be made here of the anti-ageing tripeptides of general formula X-Pro*-Pro*-Xaa-Y described in patent application WO 2015 / 181688, with Xaa chosen from Leu, Arg, Lys, Ala, Ser and Asp, at the N terminus, X chosen from H, -CO-R1and -SO2-R1and at the C terminus, Y chosen from OH, OR1, NH2, NHR1or NR1R2, R1and R2being, independently of each other, chosen from an alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurated, it being possible for said group to have a heteroatom in its backbone, in particular O, S and / or N, and Pro* corresponding to Proline, an analogue thereof or a derivative thereof; comprising, for example, Myr-PPL-OH and Myr-PPR-OH. Mention may also be made herein of the pro-pigmenting and / or pro-collagen dipeptides and tripeptides of general formula X-(Xaa1)n-Pro*-Xaa(2)-Y described in patent application WO 2014 / 080376, with n = 0, 1 or 2, Xaa1a hydrophobic amino acid chosen from Ala, Val, Met, Leu, Iso, Phe, Pro, and analogues or derivatives thereof; or a polar amino acid chosen from Ser, Thr, Tyr, Asp, Glu and derivatives and analogues thereof; and when n = 2, the two amino acids Xaa1may be identical or different; Xaa2a hydrophobic amino acid chosen from Ala, Val, Met, Leu, Iso, Phe, and analogues or derivatives thereof; a basic amino acid chosen from Arg, Lys, His, and derivatives and analogues thereof; at the N-terminus of the peptide, X is chosen from H, -CO-R1and -SO2-R1; at the C terminus of the peptide, Y is chosen from OH, OR1, NH2, NHR1or NR1R2, R1and R2being, independently of each other, chosen from alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurated, said group possibly having a heteroatom in its backbone, in particular O, S and / or N; Pro* corresponding to Proline, an analogue or a derivative thereof; comprising for example the peptides Pal-SPR-OH, Pal-PPR-OH, Pal-QPA-OH, Pal-LPA-OH, Myr-SPA-OH, Pal-PM-OH, Pal-PA-OH and Pal-PP-OH.

[0105] Tetrapeptide derivatives that may be used in the context of the present invention include, but are not limited to, Ela-KTAK (SEQ ID NO: 21), Ela-KAYK (SEQ ID NO: 22), Ela-KFYK (SEQ ID NO: 23) or Pal-KTFK (SEQ ID NO: 24).

[0106] Pentapeptide derivatives that may be used include, but are not limited to, Pal-KTTKS (SEQ ID NO: 4) (MATRIXYLTM, Sederma), Pal-KTSKS (SEQ IS NO: 5), Pal-YGGFXaa (SEQ ID NO: 25) with Xaa being Leu or Pro, or mixtures thereof.

[0107] Hexapeptide derivatives that may be used include, but are not limited to, Pal-HLDIIXaa (SEQ ID NO: 26) with Xaa being Trp, Phe, Tyr, Tic, 7-hydroxy-Tic or Tpi, Pal-GKTTKS (SEQ ID NO: 27), Pal-VGVAPG (SEQ ID NO: 28) (DERMAXYLTM, sold by Sederma).

[0108] Preferred commercially available compositions proposed by Sederma in particular include:

[0109] - tripeptides or derivatives comprising any of the following: Biopeptide-CL™, Maxi-Lip™, or Procapil™ comprising GHK;

[0110] - a tetrapeptide or derivative comprising: CrystalideTM, which contains Pal-KTFK (SEQ ID NO: 24) in a vehicle (solvated in microemulsion);

[0111] - pentapeptides or derivatives thereof such as Matrixyl ™ source of Pal-KTTKS (SEQ ID NO: 4).

[0112] Mention may also be made of:

[0113] - the Pal-GHK and Pal-GQPR (SEQ ID NO: 2) mixture (Matrixyl™ 3000), and

[0114] - the Pal-GHK and Pal-VGVAPG (SEQ ID NO: 27) mixture (Biobustyl™).

[0115] The following commercial peptides may also be mentioned as additional active ingredients:

[0116] - 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 the company Pentapharm,

[0117] - Argireline™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2(SEQ ID NO: 29) (INCI name = Acetyl hexapeptide-3), Leuphasyl™ (Tyr-D-Ala-Gly-Phe-Leu (SEQ ID NO: 30)), Aldenine™ (Gly-His-Lys), TrylagenTM(INCI name = Pseudoalteromonas Ferment Extract, Hydrolysed Wheat Protein, Hydrolysed Soy Protein, Tripeptide-10 Citrulline (reaction product of citrulline and Tripeptide-10 (synthetic peptide consisting of aspartic acid, isoleucine and lysine)), Tripeptide-1), Eyeseryl™ (Ac-β-Ala-His-Ser-His (SEQ ID NO: 31)), Serilesine™ (Ser-Ile-Lys-Val-Ala-Val (SEQ ID NO: 32)) or Decorinyl™ (INCI name: Tripeptide-10 Citrulline = reaction product of Citrulline and Tripeptide-10 (synthetic peptide consisting of aspartic acid, isoleucine and lysine) sold by the company Lipotec,

[0118] - Collaxyl™ (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID NO: 33)) or Quintescine™ (Cys-Gly) sold by the company Vincience,

[0119] - Cytokinol™LS (casein hydrolysate) sold by Laboratoires Serobiologiques / Cognis,

[0120] - Kollaren™ (Gly-His-Lys), IP2000™ (Pal-Val-Tyr-Val) or Meliprene™ (INCI name = Monofluoroheptapeptide-1: reaction product of acetic acid and a synthetic peptide containing arginine, glycine, glutamic acid, histidine, norleucine, p-fluorophenylalanine and tryptophan) sold by the European Institute of Cell Biology;

[0121] - Neutrazen™ (Pal-His-D-Phe-Arg-NH2) sold by the company Innovations; or

[0122] - BONT-L-Peptide™ (INCI name = Palmitoyl Hexapeptide-19: reaction product of palmitic acid and Hexapeptide-19 (synthetic peptide consisting of asparagine, aspartic acid, lysine and methionine), Timp-Peptide™ (INCI name = Acetyl Hexapeptide-20: product obtained by acetylation of Hexapeptide-20 (synthetic peptide consisting 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 consisting of arginine, lysine and phenylalanine) sold by the company lnfinitec Activos.

[0123] It is also possible to combine the invention with one or more cyclic peptides, in particular those extracted from linseed oil as described in the Applicant's patent application WO2019 / 149450.

[0124] The peptide(s) according to the invention or the composition containing them can be combined with at least one additional haircare ingredient, preferentially with at least one of the compounds chosen from surfactants, particular non-ionic surfactants, amphoteric surfactants and cationic surfactants, 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-acetyl-Tyr-Arg-O-hexadecyl, Pal-VGVAPG (SEQ ID NO: 27), Pal-KTTKS (SEQ ID NO: 4), Pal-KTSKS (SEQ IS NO: 4), Pal-PP, Pal-GHK, Pal-KMO2K and Pal-K(P)HG (MATRIXYL MorphomicsTM, sold by Sederma), which are conventional active agents used in topical cosmetic or dermo-pharmaceutical compositions.

[0125] According to yet another subject, the present invention provides the use of at least one peptide according to the invention as an active ingredient in the preparation of a cosmetic composition for preserving and / or improving the general condition of head hair and / or bodily hair.

[0126] A composition according to the invention may be applied to the face, body, neckline, scalp, head hair, eyelashes, bodily hair, in any form or vehicle known to those skilled in the art, in particular as a solution, dispersion, emulsion, paste or powder, individually or as a premix, or be conveyed individually or as a premix by vectors such as macrocapsules, microcapsules or nanocapsules, macrospheres, microspheres or nanospheres, liposomes, oleosomes or chylomicrons, macroparticles, microparticles or nanoparticles, macro-sponges, micro-sponges or nano-sponges, microemulsions or nanoemulsions, sequestrants or adsorbed on powdery organic polymers, talcs, bentonites, spores or exines and other mineral or organic supports.

[0127] The haircare compositions may have a variety of forms, in particular hair conditioning, hair straightening formulations, smoothing and curling products, perms, hair shampoos, pre-shampoo conditioners, after-shampoo conditioners, lotions, leave-on shampoos, styling products and leave-on hair products, waterless products, emulsions, two-in-one foaming emulsions, creams, masks, aerosol or non-aerosol foams, sprayable emulsions, emulsifier-free products, aqueous or oily sprays, serums, gels, mild sulphate-free formulations, silicone-free formulations, pigment-containing products, shower products or coloured cosmetics such as mascaras and dyeing formulations.

[0128] These haircare compositions comprising at least one peptide according to the invention may comprise various other ingredients known to those skilled in the art, for instance and without being exhaustive, cleansing agents, surfactants, conditioning agents, styling agents, anti-dandruff agents, sequestering or complexing agents (EDTA and salts thereof), stabilizing agents, nacreous and opacifying agents; plasticizing or coalescing agents, gelling agents, emollients, acidifying or basifying agents, hair growth promoters, hair loss counteracting agents, fragrances, essential oils, polymers, proteins or derivatized proteins, silicones, ceramides, sunscreen compounds, pigments, moisturizers, antioxidants, co-emulsifiers, film-forming agents, α-hydroxy acids, hair colouring agents, detergents, thickening agents, coating agents, hair conditioning agents, texturizing agents, antiseptic agents, preserving agents and surfactants.

[0129] The term "conditioning agent" means a haircare product for revitalizing hair by modifying its frictional and / or mechanical properties.

[0130] Conditioning agents may be applied to the hair when wet, for example while showering, or when the hair is dry. Usually, the term refers to the former use. The hair conditioning ingredients are generally applied from a formulation comprising the conditioning ingredients in combination with a certain number of lipophilic ingredients.

[0131] Haircare compositions are prepared using methods known to those skilled in the art. The vehicle or support excipient for the formulation may be water, oil or powder, depending on the end use of the formula: if, for example, it is a shampoo, it may be water; for other formulations, an oil is preferred: for example, plant oils (coconut, argan, jojoba, olive, sunflower, etc.), mineral oils, animal oils or synthetic oils. Synthetic esters, for instance C12-15 Alkyl Benzoate, may also be used as excipients. Liquid fatty alcohols, liquid fatty esters, solid fatty substances and in particular waxes, solid fatty esters and solid alcohols may also be used as supports.

[0132] The present invention covers a non-therapeutic, cosmetic topical treatment method for preserving and improving the appearance and general condition of hair, in particular for inducing and / or stimulating the growth of head hair, bodily hair, eyelashes and eyebrows, for protecting their structure, slowing their loss, preventing their depigmentation and / or inducing their pigmentation, comprising the topical application to head hair, bodily hair, eyelashes and / or eyebrows, of a subject in need thereof, of an effective amount of at least one peptide according to the invention or of a composition comprising same, the peptides being as defined above.

[0133] The present invention also provides a method for treating hair, which involves applying to the hair a composition comprising at least one peptide according to the invention and optionally rinsing off this composition. The method consists in applying an effective amount of at least one peptide according to the invention to the head hair and / or bodily hair in need thereof.

[0134] The "effective" amount depends on various factors, such as the person's age and condition, the severity of the disorder and the mode of administration. An effective amount means a non-toxic amount sufficient to obtain the desired effect.

[0135] According to other distinctive features, the cosmetic treatment process according to the invention may be combined with one or more other treatment processes for head hair and bodily hair, such as light therapy, heat therapy or aromatherapy.

[0136] According to the invention, it is possible to propose multi-compartment devices or kits intended for the implementation of the process described above, and which could comprise, by way of example, and without this being limiting, in a first compartment the active ingredient according to the invention and in a second compartment an excipient and / or additional active agent, the compositions contained in said first and second compartments being considered here as combination compositions for simultaneous, separate or staggered use over time in particular in one of the treatments defined above.

[0137] By way of example, for a cosmetic facial treatment, the European Cosmetics Directive has set a standard application amount for a cream of 2.72 mg / cm² / day / person, and for a body lotion of 0.5 mg / cm² / day / person.DETAILED DESCRIPTION

[0138] The present invention will be better understood in the light of the following description of an exemplary embodiment andin vitroandex vivotests.

[0139] 1. Example of preparation of an active ingredient according to the invention and of a composition comprising same

[0140] The peptides according to the invention may be obtained, for example:

[0141] - by conventional chemical synthesis, either in solid phase or in homogeneous liquid phase,

[0142] - by enzymatic synthesis starting from the constituent amino acids or derivatives thereof,

[0143] - by fermentation of a bacterial strain, modified or not by genetic engineering, to produce the desired sequences or various fragments thereof, or by extraction of proteins of animal or plant origin, preferentially plant, followed by controlled hydrolysis which releases, among other peptide fragments, H-(AA)n-Pro-Arg-OH or H-Arg- Pro-(AA)n-OH. Careful purification of the hydrolysate obtained then allows only the desired peptide to be recovered.

[0144] - by a biotechnological route, via a microorganism capable of producing same at least partly.

[0145] To perform the invention, it is possible either to extract the proteins concerned first and then hydrolyse them, or to perform hydrolysis first on a crude extract and then purify the peptide fragments. The hydrolysate may also be used without extracting the peptide fragments in question, although it must be ensured that the enzymatic hydrolysis reaction has been stopped in good time and that the presence of the peptides in question has been assayed by appropriate analytical means (tracing by radioactivity, immunofluorescence, or immunoprecipitation with specific antibodies, etc.).

[0146] Other simpler or more complex processes, leading to cheaper or purer products, may readily be envisaged by a person skilled in the art of extracting and purifying proteins and peptides.

[0147] The tetrapeptide Pal-GQPR-OH (SEQ ID NO: 2) is prepared by peptide synthesis. An arginine derivative protected on its lateral and N-terminal functions is bound by its C-terminal acid function to a resin. The N-terminal amine function of this compound is then deprotected to react with a proline derivative in the presence of 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-hydroxybenzotriazole), and the same deprotection and coupling operations are then repeated to add glutamine, glycine and palmitic acid. The totally protected peptide is then cleaved in an acidic medium and, after precipitation, washing and drying, the palmitoyl-glycyl-glutamyl-prolyl-arginine product is obtained in solid form.

[0148] To obtain the active agent according to the invention, about 500 ppm of the obtained peptide are dissolved with a surfactant, for instance steareth-20, in a matrix, for example a mixture of water and glycerol. Optionally, the active ingredient may comprise a preservative, for example potassium sorbate and / or chlorhexidine digluconate.2. Examples of cosmetic formulas

[0149] Various cosmetic formulations are described below, containing the ingredient according to the invention, in particular as formulated in the active ingredient described in point 1 above.

[0150] In the examples of cosmetic formulations described below, the active ingredient according to the invention is the RIGIN™ product (sold by Sederma) comprising the Pal-GQPR-OH (SEQ ID NO: 2) according to the invention with a surfactant and a water-glycerol matrix.

[0151] This ingredient is recommended in a composition at a content of 1% to 10%, preferably a content of between 1% and 5%, more preferably at a content of 3%. It is obvious that these contents may vary without departing from the context of the present invention, depending on the more or less pronounced effects sought.

[0152] Formulation examples are described hereinbelow. Additional active ingredients may support and / or complement the activity of the active ingredient according to the invention. These ingredients may be of any category, depending on their function(s), the place of application (body, face, neck, bust, hands, etc.), the desired end effect and the target consumer.Example 1: Shampoo

[0153] Starting materials%INCI namePhase AAquaqsWaterPotassium sorbate0.10Potassium sorbatePhase BSodium laureth sulfate8.00Sodium laureth sulfateMicrocare® Emollient DCP5.00Pentylene glycol (and) caprylyl glycol (and) decylene glycolCrodateric™ CAB 301.50Aqua (and) cocamidopropyl betainePhase CWater1.50Aqua / WaterLactic acid0.50Lactic acidPhase DActive ingredient according to the invention3.00Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Phase ESodium chloride3.00NaClProcedure

[0154] Weigh phase A and homogenize. Add the ingredients of phase B one after the other to phase A with stirring. Homogenize. Weigh phase C and homogenize. Add phase C to phase A+B with stirring. Add phase D to phase A+B+C with stirring. Add phase E to phase A+B+C+D with stirring.Examples of additional active ingredients:

[0155] Apiscalp™: active agent sold by Sederma, for combating itching, dryness and hyperseborrhea of irritated scalp (added to part D).

[0156] Zinc Pyrithione: anti-dandruff agent (added to part A).Example 2: Stimulating hair oil

[0157] Starting materials%INCI namePhase ACrodamol™ OPqsEthylhexyl palmitateCrodamol™ AB10.00C12-15 Alkyl benzoateCrodamol™ STS5.00PPG-3 Benzyl ether myristateCrodamol™ IPIS5.00Isopropyl isostearatePhenoxyethanol0.8PhenoxyethanolDL-Alpha-tocopherol0.2DL-Alpha-tocopherolPhase BCithrol™ 10GTIS15.00PEG-20 glyceryl triisostearatePentylene glycol3.00Pentylene glycolArlasolve™ DMI PC2.50Dimethyl isosorbideActive ingredient according to the invention3.00Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Procedure

[0158] Weigh phase A and homogenize. Weigh phase B and homogenize. Add phase B to phase A with stirring, homogenize. Add part C to part A+B and homogenize.Examples of additional active ingredients:

[0159] Crodabond™ CSA (INCI: Hydrogenated Castor Oil / Sebacic Acid Copolymer): active ingredient sold by Croda, which seals raised cuticles (outermost layer of the hair shaft) and repairs split ends (added to part B).

[0160] Phytolea™ Baobab EC (INCI: Adansonia Digitata Seed Oil): active ingredient sold by Crodarom, regenerating and antioxidant by virtue of its fatty acid and vitamin E and A content.

[0161] Seatons Coconut Oil (INCI: Cocos Nucifera (Coconut) Oil): active agent sold by Croda, for immediate moisturization of hair with a silky-smooth feel (added to phase A).

[0162] Apiscalp™ (INCI: Caprylic / Capric Triglyceride (and) Apium Graveolens (Celery) Seed Extract): active agent sold by Sederma, for combating itching, dryness and hyperseborrhea of irritated scalp.Example 3: Hair tonic

[0163] Starting materials%INCI namePhase ADeionized waterqsAqua / WaterAlcohol20.00AlcoholPhase BButylene glycol2.00Butylene glycolPhenoxyethanolqsPhenoxyethanolPhase CTween™ 201.50Polysorbate 20Phase DActive ingredient according to the invention3.00Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Procedure

[0164] Weigh phase A. Weigh and melt phase B. Add phase B to phase A with stirring, homogenize. Add part C to part A+B and homogenize. Add part D to part A+B+C with stirring. Homogenize.Example 4: Sulphate-free solid shampoo

[0165] Starting materials%INCI namePhase ACrodasinic™ LS3020.00Aqua (and) sodium lauroyl sarcosinatePhytofoam™5.00Aqua (and) Acacia concinna fruit extract (and) Balanites aegyptiaca fruit extract (and) Gypsophila paniculata root extractsPentylene glycol3.00Pentylene glycolArlasolve™ DMI PC2.50Dimethyl isosorbidePhase BCrodacol™ CS9019.00Cetearyl alcoholCrodazosoft™ DBQ2.00Quaternium-91 (and) cetrimonium methosulfate (and) cetearyl alcoholSyncrowax™ HRC2.00TribeheninPhase CActive ingredient according to the invention1.50Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Phase DKaolinqsKaolinProcedure

[0166] Weigh phase A and homogenize. Heat phase A to 75°C on a water bath. Weigh phase B. Heat phase B to 75°C on a water bath. Add phase C to phase A with stirring, on a water bath. Add phase B to phase A+C with stirring. Add phase D to phase A+B+C, homogenize. Pour into the mould immediately.Examples of additional active ingredients:

[0167] Matcha Tea ExtractTM(INCI: Glycerin (and) Water (and) Camellia Sinensis Leaf Extract): active ingredient sold by Crodarom, antioxidant and purifying (added to part C).

[0168] Hairspa™ (INCI: Glycerin (and) Lactitol (and) Xylitol): active ingredient sold by Sederma, calmative and moisturizing for the scalp, based on lactitol and xylitol (added to part C).Example 5: Energizing wax

[0169] Starting materials%INCI namePhase ACrodamol™ AB10.00C12-15 Alkyl benzoateOleocraft™ LP-2017.00Polyamide-8Crodamol™ IPIS5.00Isopropyl isostearateCrodamol™ ML4.00Myristyl lactateSpan™ 1202.00Sorbitan isostearateCrodamol™ STS1.00PPG-3 Benzyl ether myristateCrodazosoft™ BDQ1.00Quaternium-91 (and) cetrimonium methosulfate (and) cetearyl alcoholPhase BPentylene glycol3.00Pentylene glycolArlasolve™ DMI PC2.50Dimethyl isosorbidePhenoxyethanol0.40PhenoxyethanolPhase CCithrol™ 10GTIS15.00PEG-20 glyceryl triisostearateActive ingredient according to the invention3.00Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Procedure

[0170] Weigh phase A and heat to 80°C on a water bath. Add phase B to phase A with stirring and without heating. Weigh phase C and homogenize. When the temperature of A+B is 55°C, add phase C to A+B and homogenize. Weigh and add D to A+B+C. When the temperature of A+B+C+D is 45°C, pour into jars.Examples of additional active ingredients:

[0171] NG Shea Butter Unsaponifiables™ (INCI: Butyrospermum Parkii (Shea) Butter (and) Butyrospermum Parkii (Shea) Butter Unsaponifiables): active ingredient sold by Sederma, restores the barrier function and improves moisturization (added to phase A).

[0172] Phytolea™ Cranberry EC (INCI: Vaccinium Macrocarpon (Cranberry) Seed Oil): scalp moisturizing active ingredient sold by Crodarom (added to phase A).Example 6: Regenerating and nourishing mask

[0173] Starting materials%INCI namePhase ADeionized waterqsAqua / WaterPotassium sorbate0.10Potassium sorbatePhase BCrodacol™ CS904.50Cetearyl alcoholCrodamol™ STS4.00PPG-3 benzyl ether myristateCutissential™ behenyl 18 MEA3.00Behentrimonium methosulfate (and) C10-40 isoalkylamidopropylethyldimonium ethosulfate (and) cetyl alcoholCrodazosoft™ BDQ2.70Quaternium-91 (and) cetrimonium methosulfate (and) cetearyl alcoholCeramide HO30.20Trihydroxypalmitamidohydroxypropyl myristyl etherPhase CPentylene glycol3.00Pentylene glycolArlasolve™ DMI PC2.50Dimethyl isosorbidePhenoxyethanol0.80PhenoxyethanolPhase DUnicert Yellow 08005-J solution 0.1%0.15Aqua (and) CI 19140Phase FDeionized water1.50Aqua / Water30% sodium hydroxide0.15Sodium hydroxidePhase GActive ingredient according to the invention3.00Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Procedure

[0174] Weigh phase A and heat to 85°C on a water bath. Weigh phase B and heat to 90°C on a water bath. Weigh phase C and homogenize. Add phase C to phase A with stirring. Disperse phase B in phase A+C with stirring, homogenize. Add phase D to phase A+B+C with stirring, at about 40°C. Add phase E to phase A+B+C+D, homogenize. Add phase F to phase A+B+C+D+E, homogenize. Add phase G to phase A+B+C+D+E+F, homogenize.Examples of additional active ingredients:

[0175] Procapil™ (INCI: Butylene Glycol (and) Water (and) PPG-26-Buteth-26 (and) PEG-40 Hydrogenated Castor Oil (and) Apigenin (and) Oleanolic Acid (and) Biotinoyl Tripeptide-1) active ingredient sold by Sederma, for preventing head hair and bodily hair loss (added to phase D).

[0176] Crodarom® Manuka Honey (INCI: Water (and) Glycerin (and) Honey Extract) active ingredient sold by Crodarom, repairs damaged head hair and bodily hair (added to phase D).

[0177] Ceramide HO3 (INCI: Trihydroxypalmitamidohydroxypropyl Myristyl Ether): active ingredient sold by Sederma, helps repair damaged head hair and bodily hair and promote moisturization (added to phase B).Example 7: Infrared-protecting leave-on spray

[0178] Starting materials%INCI namePhase ADeionized waterqsAqua / WaterPotassium sorbate0.10Potassium sorbateViscaress™ HPD1.50Polyquaternium-37 (and) hydrogenated polydecene (and) trideceth-6 (and) aquaLustreplex™1.50Polyquaternium-70 (and) dipropylene glycolPhase BAlcohol5.00AlcoholPentylene glycol3.00Pentylene glycolArlasolve™ DMI PC2.50Dimethyl isosorbideTween™ 200.90Polysorbate 20Phenoxyethanol0.80PhenoxyethanolPhase CDeionized water1.00Aqua / water30% sodium hydroxide0.10sodium hydroxidePhase DVoluminis™1.00Ethyltrimonium chloride methacrylate / hydrolysed wheat protein copolymerPhase EActive ingredient according to the invention3.00Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Procedure

[0179] Weigh phase A. Weigh phase B. Add phase B to phase A with stirring. Weigh and add phase C to phase A+B with stirring. Add phase D to phase A+B+C with stirring. Add phase E to phase A+B+C+D with stirring, homogenize.Examples of additional active ingredients:

[0180] Phytessence™ Hazel Leaf (INCI: Glycerin (and) Water (and) Corylus Avellana Leaf extract): active ingredient sold by Crodarom, restoring vitality and tone to the scalp (added to phase D).

[0181] Venuceane™ (INCI: Thermus Thermophilus Ferment (and) Glycerin): active ingredient sold by Sederma, for preventing damage caused by UV and IR radiations (added to phase D).Example 8: Anti-greying serum

[0182] Starting materials%INCI namePhase ADeionized waterqsAqua / WaterCarbomer0.25CarbomerPhase BPotassium sorbate0.10Potassium sorbatePhase CDeionized water2.00Aqua / water30% sodium hydroxide0.20sodium hydroxidePhase DAlcohol5.00AlcoholPentylene glycol3.00Pentylene glycolArlasolve™ DMI PC2.50Dimethyl isosorbidePhenoxyethanol0.80PhenoxyethanolPhase EActive ingredient according to the invention3.00Aqua (and) glycerin (and) steareth-20 (and) palmitoyl tetrapeptide-7Procedure

[0183] Sprinkle the carbomer into the water and leave to swell for 30 minutes. Weigh phase B. Add phase B to phase A with stirring. Weigh and add phase C to phase A+B with stirring. Add phase D to phase A+B+C with stirring. Add phase E to phase A+B+C+D, homogenize.Example of additional active ingredients:

[0184] Neroli Floral WaterTM(INCI / Water (and) Citrus Aurantium Amara (Bitter Orange) Flower Water): active ingredient sold by Crodarom, having soothing and regenerating properties (added to phase E).

[0185] SilverfreeTM(INCI: Glycerin (and) Aqua (and) Palmitoyl-dipeptide-52): active ingredient sold by Sederma, for a long-lasting hair repigmenting effect (added to phase E).3. in vitro studies

[0186] The peptide according to the invention has a certain number of remarkable effects, as described below. The product testedin vitrocomprises the tetrapeptide Pal-GQPR-OH (SEQ ID NO: 2) prepared according to point 1 above, dissolved in an excipient. It showed activities that are presented hereinbelow.3.1. Protection of hair follicle stem cells3.1.1. Collagen XVII protectionProtocol

[0187] Human keratinocytes (HaCaTs) are cultured and then placed in contact with the product according to the invention. The cells are then treated with elastase in the presence of the product according to the invention. The cells are fixed and labelled with a primary antibody recognizing collagen XVII. Revelation of the label is performed using a fluorescent secondary antibody and photos taken under a microscope. An estimation of the cell quantity by the DNA staining method using Hoechst 33258 reagent enables normalization of the results.Results

[0188] Variation in the amount of collagen XVII in keratinocytes. Effect of the product according to the invention relative to the control (n = 18):

[0189] Collagen XVII (AFU*)Variation (%); significanceControl caseElastase-free referenceControl case + elastase-87.2%; p<0.01Reference with elastase15 ppm of Pal-GQPR + elastase+84.4%; p<0.05

[0190] * AFU: Arbitrary fluorescence units.

[0191] The results show that elastase significantly degrades collagen XVII in keratinocytes, and that the product according to the invention can counteract this effect. No toxicity was observed at the concentrations tested.Conclusion

[0192] By reducing the proteolytic activity of elastase, the product according to the invention provides protection for collagen XVII. Collagen XVII is involved in the hair stem cell niche. Loss of collagen XVII causes miniaturization of the follicle, leading to hair loss.3.1.2. Protection of HFDPC sphere formationProtocol

[0193] HFDPCs are seeded in drops ("hanging-drop") and stressed with interferon-γ in the presence of the product according to the invention. The drops are then transferred to the wells of a new plate. The spheres are then fixed, and their sizes determined by image analysis.Results

[0194] Variation in sphere diameter of interferon-γ-stressed HFDPCs. Effect of the product according to the invention (n ≥ 10):

[0195] Diameter of the HFDPC spheresVariation (%); significanceControl caseUnstressed referenceControl case + interferon-γ-63.4%; p<0.01Interferon-γ-stressed reference20 ppm of Pal-GQPR + interferon-γ+76.2%; p<0.01

[0196] The results show that interferon-γ inhibits the formation of HFDPC spheres, with the spheres having a smaller diameter. The results also show that the product according to the invention protects cells from the effect of interferon-γ by significantly stimulating the diameter of the HFDPC spheres. No toxicity was observed at the concentrations tested.Conclusion

[0197] In the presence of a pro-inflammatory stress such as interferon-γ which induces the catagen phase, the product according to the invention has a protective effect on the formation of the spherical structure of HFDPCs, more particularly on the diameter of HFDPC spheres, allowing the proper development of hair follicles.3.2. Hair growth and morphogenesis3.2.1. Proliferation of HFDPCsProtocol

[0198] HFDPCs are seeded in their growth medium. After 24 hours, the culture medium is changed to a test medium, and the cells are incubated for 24 hours to acclimatize to this new medium. The product according to the invention and the EdU probe are placed in contact with the cells for 24 hours. Following this contact, the cells are rinsed with a PBS solution, fixed and then permeabilized. The EdU detection reagent is added for 30 min.

[0199] An estimation of the cell quantity by the DNA staining method using Hoechst 33258 reagent enables normalization of the results.Results

[0200] Variation in HFDPC proliferation. Effect of the product according to the invention relative to the control case (n = 4):

[0201] Proliferation of the HFDPCsVariation (%); significanceControl caseReference10 ppm of Pal-GQPR+9.7%; nsd15 ppm of Pal-GQPR+23.7%; p<0.0120 ppm of Pal-GQPR+51.8%; p<0.01

[0202] *nsd: non-significant difference

[0203] The results show that the product according to the invention significantly increases the proliferation of HFDPCs, and that there is a dose effect. No toxicity was observed at the concentrations tested.3.2.2. Hyaluronic acidProtocol

[0204] HFDPC cells are grown to confluence in their culture medium. The cells are then placed in contact with the product according to the invention. Following this contact, the culture supernatants are assayed for their hyaluronic acid content. The cell carpets are observed under the microscope to check for absence of toxicity. A survival test and an estimation of the cell quantity by the DNA staining method using Hoechst 33258 reagent enables normalization of the results.Results

[0205] Variation in hyaluronic acid production by HFDPC cells. Effect of the product according to the invention relative to the control (n = 5):

[0206] Hyaluronic acid (ng / 106cell)Variation (%); significanceControl caseReference10 ppm of Pal-GQPR+20%; nsd15 ppm of Pal-GQPR+34%; p<0.0530 ppm of Pal-GQPR+309%; p<0.01

[0207] The results show that the product according to the invention significantly increases hyaluronic acid synthesis by HFDPC cells, and that there is a dose effect. No toxicity was observed at the concentrations tested.3.2.3. Gene expressionProtocol

[0208] HFDPCs are seeded in their growth medium. After 24 hours, a purge is performed in serum-free medium, and the product according to the invention is then placed in contact for 6 hours and 24 hours. Following this contact, the cells are lysed, and their RNA extracted. After RNA quantification by NanoDrop spectrophotometry, reverse transcription followed by qPCR is performed to determine the level of expression of the HAPLN1 and TGF-β2 genes of interest. The data are normalized using a housekeeping gene. The levels of expression change relative to solvent controls are expressed as a ratio and are calculated according to the formula: 3.2.3.1. HAPLN1Results

[0209] Variation in HAPLN1 gene expression in HFDPCs. Effect of the product according to the invention relative to the control (n = 3):

[0210] HAPLN1Ratio R at 24 hoursControl case×1.01 -Reference20 ppm of Pal-GQPR×1.59; p<0.01

[0211] The results show that the product according to the invention significantly increases HAPLN1 gene expression in HFDPCs relative to the control. No toxicity was observed at the concentrations tested.3.2.3.2. TGF-β2Results

[0212] Variation in TGF-β2 gene expression in HFDPCs. Effect of the product according to the invention relative to the control (n = 3):

[0213] TGF-β2Ratio R at 6 hoursRatio R at 24 hoursControl case×1.00 -Reference×1.00 -Reference15 ppm of Pal-GQPR×1.48; p<0.05×1.34; p<0.0520 ppm of Pal-GQPR×1.50; p<0.01×1.61; p<0.01

[0214] The results show that the product according to the invention significantly increases TGF-β2 gene expression in HFDPCs relative to the control. No toxicity was observed at the tested concentrations.3.2.4. Metabolic signalling pathwaysProtocol

[0215] HFDPCs are placed in contact with the product according to the invention. Following this contact, the intracellular amount of phosphorylated proteins AKT and ERK (noted respectively as pAKT and pERK) is evaluated using the ELISA method.

[0216] Estimation of the total protein amount using a BCA quantification method enables normalization of the results.Results

[0217] Variation in AKT and ERK phosphorylation in HFDPC cells after 24 hours of contact. Effect of the product according to the invention relative to the control case (n = 4):

[0218] Variation (%); significanceControl caseReferencepAKTReferencepERK15 ppm of Pal-GQPR+23%; nsd+59%; p<0.0120 ppm of Pal-GQPR+46%; p<0.05+107%; p<0.01

[0219] The results show that the product according to the invention increases phosphorylation of AKT and ERK proteins in HFDPC cells.3.2.5. Conclusion

[0220] The product according to the invention allows hyaluronic acid synthesis by HFDPCs to be enhanced, thus ensuring a good state of moisturization of the hair follicle and scalp. By binding to CD44, hyaluronic acid induces phosphorylation of the AKT protein to activate the corresponding metabolic pathway.

[0221] The product according to the invention also allows expression of the HAPLN1 and TGF-β2 genes, linked respectively to protection against hyaluronic acid degradation and induction of phosphorylation of the ERK protein which activates the corresponding metabolic pathway.

[0222] Activating the ERK and AKT metabolic pathways makes it possible to induce proliferation of the HFDPCs responsible for hair growth and morphogenesis.

[0223] 3.3. Protecting hair against different types of stress

[0224] Hair follicles are exposed on a daily basis to stresses such as psychological, inflammatory, hormonal, oxidative etc. stresses. These stresses have a direct or indirect impact on their metabolism, causing problems with hair growth and loss. Hair growth is stopped by induction of the catagen phase and / or shortening of the anagen phase. These events are also correlated with reduced proliferation of HFDPCs.

[0225] Psychological stress, represented here by stressing HFDPCs with hydrocortisone (cortisol) or dexamethasone (synthetic glucocorticoid), decreases HFDPC proliferation and inhibits hair growth. Dexamethasone also reduces the cell viability of HFDPCs and induces the catagen phase in HFDPCs.

[0226] Inflammatory stress, represented here by interferon-γ stress of HFDPCs, induces the catagen phase in HFDPCs.

[0227] Oxidative stress, represented here by H2O2stress of HFDPCs, causes damage to DNA, proteins and lipids, leading to greying and hair loss.

[0228] Hormonal stress, represented here by dihydrotestosterone stress of HFDPCs, induces shortening of the anagen phase in HFDPCs.3.3.1. Psychological stress3.3.1.1. Hydrocortisone3.3.1.1.1. Proliferation of HFDPCsProtocol

[0229] HFDPCs are seeded in their growth medium. After 24 hours, the culture medium is changed to a test medium, and the cells are incubated for 24 hours to acclimatize to this new medium. Hydrocortisone, the product according to the invention and the EdU probe are then placed in contact with the cells for 24 hours. The cells are rinsed with PBS solution, fixed and then permeabilized. The EdU detection reagent is added for 30 min.

[0230] An estimation of the cell quantity by the DNA staining method using Hoechst 33258 reagent enables normalization of the results.Results

[0231] Variation in proliferation of hydrocortisone-stressed HFDPCs. Effect of the product according to the invention relative to the control case (n = 4):

[0232] Proliferation of HFDPCsVariation (%); significanceVariation (%); significanceControl caseUnstressed referenceControl case + hydrocortisone-29.9%; p<0.01Hydrocortisone-stressed reference10 ppm of Pal-GQPR + hydrocortisone+195.6%; p<0.0115 ppm of Pal-GQPR + hydrocortisone+389.7%; p<0.01

[0233] The results show that hydrocortisone significantly reduces the proliferation of HFDPCs, and that the product according to the invention allows this effect to be counteracted. There is a dose effect. No toxicity was observed at the concentrations tested.3.3.1.1.2. Hyaluronic acidProtocol

[0234] A protocol equivalent to that described in section 3.2.2. is performed with a few modifications: when placing the product according to the invention in contact with HFDPC cells, the cells were also treated with hydrocortisone.Results

[0235] Variation in hyaluronic acid production by hydrocortisone-stressed HFDPCs. Effect of the product according to the invention relative to the control (n = 5):

[0236] Hyaluronic acid (ng / 106cell)Variation (%); significanceVariation (%); significanceControl caseUnstressed referenceControl case + hydrocortisone-58%; p<0.01Hydrocortisone-stressed reference20 ppm of Pal-GQPR + hydrocortisone+37%; p<0.05

[0237] The results show that the product according to the invention significantly increases hyaluronic acid synthesis by HFDPCs when they are stressed with hydrocortisone. No toxicity was observed at the concentrations tested.3.3.1.2. Dexamethasone3.3.1.2.1. Proliferation of HFDPCsProtocol

[0238] The protocol is equivalent to that above for hydroxycortisone (cf. paragraph 3.3.1.1.1.), only the stress molecule used is different: hydroxycortisone is replaced with dexamethasone.Results

[0239] Variation in proliferation of dexamethasone-stressed HFDPCs. Effect of the product according to the invention relative to the control case (n = 4):

[0240] Proliferation of HFDPCsVariation (%); significanceVariation (%); significanceControl caseUnstressed referenceControl case + dexamethasone-30.3%; p<0.01Dexamethasone-stressed reference10 ppm of Pal-GQPR + dexamethasone+86.9%; p<0.0115 ppm of Pal-GQPR + dexamethasone+138.5%; p<0.01

[0241] The results show that the product according to the invention significantly increases the proliferation of HFDPCs when they are stressed with dexamethasone, and that there is a dose effect. No toxicity was observed at the concentrations tested.3.3.2. Inflammatory stress3.3.2.1. Interferon-γ3.3.2.1.1. Proliferation of HFDPCsProtocol

[0242] The protocol is equivalent to that above for hydroxycortisone (cf. paragraph 3.3.1.1.1.), only the stress molecule used is different: hydroxycortisone is replaced with interferon-γ.Results

[0243] Variation in proliferation of HFDPCs stressed with interferon-γ. Effect of the product according to the invention relative to the control case (n = 4):

[0244] Proliferation of HFDPCsVariation (%); significanceVariation (%); significanceControl caseUnstressed referenceControl case + interferon-γ-40.9%; p<0.01Interferon-γ-stressed reference10 ppm of Pal-GQPR + interferon-γ+146.5%; p<0.0115 ppm of Pal-GQPR + interferon-γ+322.6%; p<0.01

[0245] The results show that the product according to the invention significantly increases the proliferation of HFDPCs when they are stressed with interferon-γ, and that there is a dose effect. No toxicity was observed at the concentrations tested.3.3.2.1.2. Hyaluronic acidProtocol

[0246] A protocol equivalent to that described in section 3.2.2. is performed with a few modifications: when placing the product according to the invention in contact with the HFDPC cells, the cells also received interferon-γ.Results

[0247] Variation in hyaluronic acid production by interferon-γ-stressed HFDPCs. Effect of the product according to the invention relative to the control (n = 5):

[0248] Hyaluronic acid (ng / 106cell)Variation (%); significanceVariation (%); significanceControl caseUnstressed referenceControl case + interferon-γ-35%; p<0.01Interferon-γ-stressed reference20 ppm of Pal-GQPR + interferon-γ+72%; p<0.01

[0249] The results show that the product according to the invention significantly increases hyaluronic acid synthesis by HFDPCs when they are stressed with interferon-γ. No toxicity was observed at the concentrations tested.3.3.2.1.3. TGF-β2Protocol

[0250] A protocol equivalent to that described in section 3.2.3. is performed with a few modifications: when the product according to the invention is placed in contact with HFDPC cells, the cells also receive interferon-γ.Results

[0251] Variation in TGF-β2 gene expression in interferon-γ-stressed HFDPCs after 6 h (n = 4) and 24 h (n = 4) of contact. Effect of the product according to the invention relative to the control:

[0252] TGF-β2Ratio R after 6 hoursRatio R after 24 hoursControl caseUnstressed referenceUnstressed referenceControl case + interferon-γ× 0.18; p<0.01Interferon-γ-stressed reference× 0.43; p<0.01Interferon-γ-stressed reference10 ppm of Pal-GQPR×1.38; p<0.01×1.35; p<0.05

[0253] The results show that the product according to the invention significantly increases TGF-β2 gene expression in HFDPCs when they are stressed with interferon-γ. This makes it possible to counteract the effect of inflammatory stress, which inhibits TGF-β2 gene expression in HFDPCs. No toxicity was observed at the concentrations tested.3.3.3. Oxidative stress3.3.3.1. Proliferation of HFDPCsProtocol

[0254] The protocol is equivalent to that above for hydroxycortisone (cf. paragraph 3.3.1.1.1.), only the stress molecule used is different: hydroxycortisone is replaced with H2O2.Results

[0255] Variation in proliferation of H2O2-stressed HFDPCs. Effect of the product according to the invention relative to the control case (n = 4):

[0256] Proliferation of HFDPCsVariation (%); significanceVariation (%); significanceControl caseUnstressed referenceControl case + H2O2-21.3%; p<0.01H2O2-stressed reference10 ppm of Pal-GQPR + H2O2+151.1%; p<0.0115 ppm of Pal-GQPR + H2O2+322.8%; p<0.01

[0257] The results show that the product according to the invention significantly increases the proliferation of HFDPCs when they are stressed with H2O2, and that there is a dose effect. No toxicity was observed at the tested concentrations.3.3.4. Hormonal stress3.3.4.1. Proliferation of HFDPCsProtocol

[0258] The protocol is equivalent to that above for hydroxycortisone (cf. paragraph 3.3.1.1.1.), only the stress molecule used is different: hydroxycortisone is replaced with dihydrotestosterone.Results

[0259] Variation in proliferation of dihydrotestosterone-stressed HFDPCs. Effect of the product according to the invention relative to the control case (n = 4):

[0260] Proliferation of HFDPCsVariation (%); significanceVariation (%); significanceControl caseUnstressed referenceControl case + dihydrotestosterone-25.3%; p<0.01Dihydrotestosterone-stressed reference10 ppm of Pal-GQPR + dihydrotestosterone+144.5%; p<0.0115 ppm of Pal-GQPR + dihydrotestosterone+271.6%; p<0.01

[0261] The results show that the product according to the invention significantly increases the proliferation of HFDPCs when they are stressed with dihydrotestosterone, and that there is a dose effect. No toxicity was observed at the tested concentrations.3.3.5. Conclusion

[0262] The product according to the invention protects the hair follicle from the various stresses encountered on a daily basis by significantly increasing HFDPC proliferation, TGF-β2 gene expression and hyaluronic acid synthesis in HFDPCs, all of which are responsible for head hair and / or bodily hair growth and morphogenesis.3.4. Protection of the extracellular matrix3.4.1. FibroblastsProtocol

[0263] Normal human fibroblasts are grown to confluence and then placed in contact with the product according to the invention. Following this contact, the culture supernatants and cell lawns are assayed for their content of collagens, hyaluronic acid, fibronectins and laminins using ELISA-type kits. An estimation of the cell quantity by the DNA staining method using Hoechst 33258 reagent enabled normalization of the results.3.4.1.1. Collagen I and collagen IVResults

[0264] Variation in collagen I (n = 5) and collagen IV (n = 5) production by fibroblasts. Effect of the product according to the invention relative to the control:

[0265] Collagen I (ng / 106cell)Variation (%); significanceCollagen IV (ng / 106cell)Variation (%); significanceControl caseReferenceReference12 ppm of Pal-GQPR+89%; p<0.01+67%; p<0.0115 ppm of Pal-GQPR+113%; p<0.01+89%; p<0.01

[0266] The results show that the product according to the invention significantly increases the synthesis of collagen I and collagen IV by fibroblasts, essential elements of the ECM, and that there is a dose effect. No toxicity was observed at the tested concentrations.3.4.1.2. Hyaluronic acidResults

[0267] Variation in hyaluronic acid production by fibroblasts. Effect of the product according to the invention relative to the control (n = 5):

[0268] Hyaluronic acid (ng / 106cell)Variation (%); significanceControl caseReference12 ppm of Pal-GQPR+90%; p<0.0115 ppm of Pal-GQPR+145%; p<0.01

[0269] The results show that the product according to the invention significantly increases hyaluronic acid synthesis by fibroblasts, and that there is a dose effect. No toxicity was observed at the tested concentrations.3.4.1.3. FibronectinResults

[0270] Variation in fibronectin production by fibroblasts. Effect of the product according to the invention relative to the control (n = 5):

[0271] Fibronectin (ng / 106cell)Variation (%); significanceControl caseReference12 ppm of Pal-GQPR+37%; p<0.0115 ppm of Pal-GQPR+60%; p<0.01

[0272] The results show that the product according to the invention significantly increases fibronectin synthesis by fibroblasts, and that there is a dose effect. No toxicity was observed at the tested concentrations.3.4.1.4. LamininsResults

[0273] Variation in laminin production by fibroblasts. Effect of the product according to the invention relative to the control (n = 5):

[0274] Laminins (ng / 106cell)Variation (%); significanceControl caseReference12 ppm of Pal-GQPR+45%; p<0.0115 ppm of Pal-GQPR+47%; p<0.01

[0275] The results show that the product according to the invention significantly increases laminin synthesis by fibroblasts. No toxicity was observed at the tested concentrations.3.4.2. KeratinocytesProtocol

[0276] Normal human keratinocytes are cultured until a confluent lawn is produced. At this stage, they are placed in contact with the product according to the invention for 24 hours, and the carpets are then irradiated with UVB and placed in contact again with the product according to the invention for 24 hours. The amount of IL-6 synthesized is measured in the culture supernatants by ELISA assay.

[0277] An estimation of the cell quantity by the DNA staining method using Hoechst 33258 reagent enables normalization of the results.Results

[0278] Variation in IL-6 production by UVB-irradiated and non-irradiated keratinocytes. Effect of 15 ppm Pal-GQPR relative to the control (n = 2):

[0279] Non-irradiated cellsIL-6 (pg / 106cell)UVB-irradiated cellsIL-6 (pg / 106cell)Control caseNon-irradiated referenceIrradiated referenceVariation (%) relative to the control case-27%-48%

[0280] The results show that the product according to the invention strongly reduces IL-6 production by both UVB-irradiated and non-irradiated keratinocytes. No toxicity was observed at the tested concentration.3.4.3. Melanocytes3.4.3.1. MelaninProtocol

[0281] Normal human skin melanocytes (NHM) are cultured and placed in contact for 10 days with the product according to the invention. Following this contact, the cell carpets are crushed, and the melanin is extracted from the cells. The amount of melanin is evaluated spectrophotometrically at 490 nm, using a standard range previously established from a melanin solution. A protein assay using the bicinchoninic acid (BCA) method allows the cell quantity to be estimated, to homogenize the data obtained.Results

[0282] Variation in melanin production by melanocytes. Effect of the product according to the invention relative to the control (n = 4):

[0283] Melanin (µg / mL / 106cell)Variation (%); significanceControl caseReference15 ppm of Pal-GQPR+18%; p<0.0120 ppm of Pal-GQPR+31%; p<0.0130 ppm of Pal-GQPR+45%; p<0.01

[0284] The results show that the product according to the invention significantly increases melanin synthesis by melanocytes in a dose-dependent manner. No toxicity was observed at the concentrations tested.3.4.3.2. Tyrosinase activityProtocol

[0285] Normal human skin melanocytes (NHM) are cultured and placed in contact for 10 days with the product according to the invention. Following the contact, the cell carpets are crushed, the tyrosinase is extracted from the cells and its dopa-oxidase activity is evaluated using the substrate L-DOPA at 37°C. Absorbance due to dopaquinone production is measured at 490 nm and converted into activity units using a preset range. Protein assaying via the Bicinchoninic Acid (BCA) method allows the cell quantity to be estimated and thus homogenizing the data obtained.Results

[0286] Variation in tyrosinase activity in melanocytes. Effect of the product according to the invention relative to the control (n = 4):

[0287] Tyrosinase (µg / mL / 106cell)Variation (%); significanceControl caseReference15 ppm of Pal-GQPR+18%; p<0.0120 ppm of Pal-GQPR+21%; p<0.0130 ppm of Pal-GQPR+20%; p<0.01

[0288] The results show that the product according to the invention significantly increases tyrosinase activity in the melanocytes. No toxicity was observed at the concentrations tested.3.4.4 Conclusion

[0289] The product according to the invention induces the synthesis of ECM proteins in fibroblasts, allowing better anchoring and growth of head hair and / or bodily hair, reducing its loss and preserving and / or improving the general condition of the head hair and / or bodily hair. The product according to the invention reduces the basal or UVB-induced inflammation responsible for inducing early onset of the catagen phase of the hair cycle, during which the hair follicle is no longer nourished, and the hair falls out. The product according to the invention allows this effect to be counteracted.

[0290] The product according to the invention also induces melanin production and tyrosinase activity in melanocytes, demonstrating pro-pigmenting activity and the cosmetic use that may result therefrom, for example anti-greying use for head hair and bodily hair.4. Ex vivo study4.1. Growth of bodily hair from hair folliclesProtocol

[0291] Hair follicles from Philpott facelift surgery are incubated for 7 days with the product according to the invention. The medium is renewed on the second and fifth day. The length of the hair coming from the follicle is measured by image analysis of photos taken on D0, D2, D5 and D7.Results

[0292] Variation in length of the hair coming from the follicle between D0 and D7. Effect of the product according to the invention relative to the control (n = 12):

[0293] Hair lengthVariation (%); significanceControl caseReference15 ppm of Pal-GQPR+32%; p<0.05

[0294] The results show that the product according to the invention significantly stimulates hair growth from the hair follicle.

Claims

Use of at least one peptide of formula X-(Xaa)nGQPR(Xaa)m-Z, in which:Xaa is an amino acid chosen from proline (P, Pro), glycine (G, Gly), alanine (A, Ala), valine (V, Val), leucine (L, Leu) and isoleucine (I, Ile), the Xaa being chosen independently of each other, with n and m integers which may be identical or different comprised between 0 and 5;at the N-terminus X is chosen from H, CO-R1or SO2-R1;at the C-terminus Z is chosen from OH, OR1, NH2, NHR1or NR1R2;R1and R2being, independently of each other, chosen from an alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurated, said group containing from 1 to 24 carbon atoms and possibly having in its backbone one or more heteroatoms O, S and / or N;for non-therapeutic cosmetic treatment of head hair and / or bodily hair, including eyelashes and eyebrows.Use according to claim 1, characterized in that the hair treatment is suitable for:protecting the structure of head hair and / or bodily hair, including eyelashes and eyebrows; and / orslowing down the loss of head hair and / or bodily hair, including eyelashes and eyebrows;inducing and / or stimulating the growth of head hair and / or bodily hair, including eyelashes and eyebrows;preventing depigmentation and / or inducing pigmentation of head hair and / or bodily hair, including eyelashes and eyebrows.Use according to claim 1 or 2, characterized in that the treatment is suitable for protecting hair follicle stem cells.Use according to any one of the preceding claims, characterized in that the treatment is suitable for protecting the dermal papillae of the hair follicles.Use according to any of the preceding claims, characterized in that the treatment is suitable for preventing dry, rough, brittle, dull and / or split-end hair.Use according to any one of the preceding claims, characterized in that R1and / or R2are lipophilic chains of 3 to 24 carbon atoms.Use according to any one of the preceding claims, characterized in that X is an acyl group CO-R1.Use according to any one of the preceding claims, characterized in that the group X is an acyl chosen, independently of each other, from octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl and lipoyl.Use according to any one of the preceding claims, characterized in that Z is chosen from an OH or NH2group.Use according to any one of the preceding claims, characterized in that the peptide is Pal-GQPR-OH or Pal-GQPR-NH2.Use according to any one of the preceding claims, characterized in that the peptide is optionally combined with one or more additional active ingredients in a physiologically acceptable medium.Haircare composition comprising at least one peptide of formula X-(Xaa)nGQPR(Xaa)m-Z, in which:Xaa is an amino acid chosen from proline (P, Pro), glycine (G, Gly), alanine (A, Ala), valine (V, Val), leucine (L, Leu) and isoleucine (I, Ile), the Xaa being chosen independently of each other, with n and m integers which may be identical or different comprised between 0 and 5;at the N-terminus X is chosen from H, CO-R1, or SO2-R1;at the C-terminus Z is chosen from OH, OR1, NH2, NHR1, or NR1R2;R1and R2being, independently of each other, chosen from an alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfurated, said group containing from 1 to 24 carbon atoms and possibly having in its backbone one or more heteroatoms O, S and / or N;and a physiologically acceptable medium.Composition according to claim 12, also comprising at least one additional bodily hair or head hair care ingredient.Composition according to claim 13, in which the additional bodily hair or head hair care ingredient is: one or more surfactants, vitamin B3 compounds, niacinamide, tocopherol, retinol, hexamidine, α-lipoic acid, resveratrol, DHEA, hyaluronic acid, ceramides, one or more peptides.Composition according to claim 13 or 14, in which the peptide(s) may be Pal-GHK and / or Pal-PP.Composition according to any one of claims 13 to 15, in which the surfactant is chosen from a non-ionic surfactant, an amphoteric surfactant and a cationic surfactant.

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