Peptides that promote hair growth and inhibit hair loss and their uses

Abstract

This invention relates to peptides with activity that promotes hair growth or prevents or inhibits hair loss. The peptides of this invention promote the proliferation of human follicular dermal papilla cells (HFDPC), activate cell proliferation-related signaling proteins and β-catenin in HFDPC, enhance the expression levels of downstream genes of β-catenin, downregulate the expression level of the hair loss protein DKK-1, increase the expression of keratin in hair follicle outer root sheath cells (HORSC), and upregulate the expression of transcription factors involved in cell activation in germinal stromal cells (GMC).

Description

Technical Field

[0001] This invention relates to peptides that have the activity of promoting hair growth and inhibiting hair loss, and their uses. Background Technology

[0002] Alopecia is a condition caused by an excessive amount of hair loss due to a longer telogen phase than normal or an increase in the number of hair follicles in the telogen phase. It is caused by factors such as stress, nutritional deficiencies, local blood flow disorders, hormones, and genetics, and the hair loss is irreversible.

[0003] As a treatment for hair loss, 5α-reductase inhibitors convert the male hormone testosterone into the androgen dihydrotestosterone (DHT). For example, drugs such as finasteride or dutasteride have been developed and approved for commercial sale, and minoxidil, a drug that promotes hair growth by stimulating hair follicles and increasing blood flow, has also been approved and used.

[0004] However, for 5α-reductase inhibitors, side effects such as sexual dysfunction, depression, anxiety, and breast enlargement have been reported to occur relatively frequently; while for minoxidil, side effects such as electrocardiogram abnormalities, tachycardia, and endocarditis have been reported; in addition, it has been reported that hair loss will start again once minoxidil is discontinued.

[0005] Peptides are highly biocompatible and, when used as a single active ingredient in pharmaceuticals or cosmetics, have fewer side effects compared to extracts that include various components. After inhibiting localized hair loss, these peptides are readily broken down and eliminated by proteases in the body; therefore, there are fewer concerns about the side effects of these peptide-based medications compared to existing therapeutic agents.

[0006] PCT international patent application WO 2005-082395 discloses a peptide that promotes hair growth by facilitating the transition from the resting phase to the anagen phase during the hair growth cycle. Korean patent No. 10-2387764 discloses a peptide derivative in dimer form that promotes the proliferation of hair follicle cells.

[0007] [Existing technical documents]

[0008] [Patent Literature]

[0009] WO 2005-082395

[0010] Korean Patent No. 10-2387764 Summary of the Invention

[0011] Technical issues

[0012] The inventors conducted research to develop peptides that exhibit improved activity in promoting hair growth and inhibiting hair loss, while effectively promoting hair growth with fewer side effects. As a result, the inventors experimentally demonstrated that their newly developed peptides promote the proliferation of human follicular dermal papilla cells (HHFDPC), activate cell proliferation-related signaling proteins, activate β-catenin, improve the expression levels of downstream factors of β-catenin such as LEF-1, c-Myc, and Cyclin D1, downregulate the expression level of the hair loss protein DKK-1 in HHFDPC, increase the expression of keratin in outer root sheath cells (HORSC), and increase the expression of transcription factors involved in cell activation, such as MSX2, HOXC13, and FOXN1, in human hair growth stromal cells (HHGMC), thus completing this invention.

[0013] Therefore, the object of the present invention is to provide novel peptides that have the activity of promoting hair growth and inhibiting hair loss.

[0014] Another object of the present invention is to provide a composition for promoting hair growth, or inhibiting, preventing or improving hair loss, the composition comprising a peptide having the above-mentioned activity as an active ingredient.

[0015] Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of hair loss.

[0016] Another object of the present invention is to provide a cosmetic composition for promoting hair growth or inhibiting or improving hair loss.

[0017] Technical solution

[0018] In order to achieve the above objectives,

[0019] One aspect of the present invention provides a peptide comprising the amino acid sequence of SEQ ID NO: 1.

[0020] Another aspect of the present invention provides a composition for promoting hair growth, or inhibiting, preventing or improving hair loss, the composition comprising the peptide as an active ingredient.

[0021] Another aspect of the present invention provides a pharmaceutical composition for the prevention or treatment of hair loss, the pharmaceutical composition comprising the peptide as an active ingredient.

[0022] Another aspect of the present invention provides a cosmetic composition for promoting hair growth or preventing or improving hair loss, the cosmetic composition comprising the peptide as an active ingredient.

[0023] The present invention will be described in detail below.

[0024] 1. Peptides and their activities

[0025] According to one aspect of the invention, a peptide comprising the amino acid sequence disclosed in SEQ ID NO: 1 is provided.

[0026] As used in this article, the term "peptide" refers to a linear molecule formed by amino acid residues linked together by peptide bonds.

[0027] The peptide comprising the amino acid sequence of SEQ ID NO: 1 of the present invention may be used without modification, but variations thereof having different amino acid sequences or fragments thereof may also be used, without affecting the original activity of the peptide (such as the activity of promoting hair growth or inhibiting hair loss).

[0028] The peptides of the present invention can be modified by phosphorylation, sulfation, acrylate, glycosylation, methylation, farnesylation, etc., as long as the activity of the peptide is not changed.

[0029] The peptides of the present invention comprise: peptides comprising an amino acid sequence substantially identical to that of the peptide comprising the amino acid sequence of SEQ ID NO:1, and variants or active fragments thereof. A substantially identical amino acid sequence is defined as an amino acid sequence having at least 75%, for example, at least 80%, at least 85%, at least 90%, at least 95%, or at least 97% sequence identity with the amino acid sequence of SEQ ID NO:1. Furthermore, the peptide may additionally comprise a targeting sequence, a tag, labeled residues, and amino acid sequences prepared for a specific purpose of increasing half-life or peptide stability.

[0030] The peptides of the present invention may have induced N-terminal and / or C-terminal modifications to select a portion of the amino acid sequence and increase their activity. These N-terminal and / or C-terminal modifications can significantly improve the stability of the peptides of the present invention, for example, increasing the half-life of the peptide when administered in vivo. The term "stability" encompasses not only in vivo stability (which protects the peptides of the present invention from attack by in vivo protein-cleaving enzymes) but also storage stability (e.g., storage stability at room temperature).

[0031] N-terminal modification can be a modification in which a protecting group selected from the group consisting of acetyl, fluorenylmethoxycarbonyl, formyl, palmitoyl, myristyl, stearyl, and polyethylene glycol (PEG) is attached to the N-terminus of the peptide. C-terminal modification can be a modification in which a hydroxyl (-OH), amino (-NH2), hydrazide (-NHNH2), etc., are attached to the C-terminus of the peptide, but is not limited to these.

[0032] The peptides of the present invention can be prepared by a variety of methods widely known in the art to which this invention pertains. For example, the peptides of the present invention can be prepared using chemical synthesis methods known in the art, especially solid-phase synthesis techniques (Merrifield, J. Amer. Chem. Soc. 85: 2149-54 (1963); Stewart, et al., Solid Phase Peptide Synthesis, 2nd ed., Pierce Chem. Co.: Rockford, 111 (1984)) or liquid-phase synthesis techniques (US Patent No. 5516891).

[0033] The peptides of this invention have the activity of promoting hair growth or preventing or inhibiting hair loss.

[0034] In an embodiment, the peptide of the present invention promotes the proliferation of follicular dermal papillary cells (HFDPC).

[0035] In embodiments, the peptides of the present invention activate Akt or ERK, which are proteins involved in signal transduction in follicular dermal papillary cells (HFDPC).

[0036] In an embodiment, the peptide of the present invention activates β-catenin in follicular dermal papillary cells (HFDPC) and promotes its migration to the cell nucleus.

[0037] In an embodiment, the peptide of the present invention upregulates the gene expression of one or more factors selected from the group consisting of LEF-1, c-Myc, and cyclin D1, which are downstream factors of β-catenin, in follicular dermal papillary cells (HFDPC).

[0038] In this embodiment, the peptide of the present invention downregulates the expression level of the hair loss protein DKK-1 (Dickkopf-1) in follicular dermal papillary cells (HFDPC). In hair follicles, dihydrotestosterone (DHT) promotes the expression of DKK-1, and it is known that DHT-induced DKK-1 inhibits the proliferation of keratinocytes in hair follicles, induces their apoptosis, and thus promotes hair loss (J of Invest Dermatolo. 2008, Feb., 128(2), pp. 262-269.). Dihydrotestosterone (DHT) increases the expression level of the hair loss protein DKK-1, and the peptide of the present invention downregulates the DHT-increased expression level of DKK-1.

[0039] In an embodiment, the peptide of the present invention increases gene expression of one or more proteins selected from the group consisting of Ha3-II, keratin 5, keratin 14 and keratin 19 in human hair follicle outer root sheath cells (HHORSC).

[0040] In an embodiment, the peptide of the present invention increases the expression of one or more transcription factors selected from the group consisting of MSX2, HOXC13 and FOXN1 in human hair follicle stromal cells (HHGMC).

[0041] Through the activities mentioned above, the peptides of the present invention can exhibit the effects of promoting hair growth, or inhibiting, preventing or improving hair loss.

[0042] 2. Compositions used to promote hair growth, or to prevent, treat, or improve hair loss.

[0043] In another aspect of the invention, a composition is provided for promoting hair growth, or for preventing, treating or improving hair loss, the composition comprising: a peptide comprising the amino acid sequence of SEQ ID NO: 1 as an active ingredient.

[0044] As described above, the peptide of the present invention comprising the amino acid sequence of SEQ ID NO: 1 has the activity of promoting hair growth or inhibiting or preventing hair loss.

[0045] In another aspect of the invention, the compositions of the invention provide a pharmaceutical composition for the prevention or treatment of hair loss, the pharmaceutical composition comprising: a peptide comprising the amino acid sequence of SEQ ID NO: 1 as an active ingredient.

[0046] As used herein, the terms "hair loss" or "hair loss" refer to the absence of hair in areas where hair should normally be present, or a reduction in the amount of hair compared to a normal state, due to abnormal hair loss. In embodiments, hair loss or symptoms of hair loss in this invention include hair loss on the scalp.

[0047] In this invention, hair loss includes, but is not limited to, hereditary androgenetic alopecia (male pattern baldness), female pattern baldness, telogen effluvium, anagen effluvium, alopecia areata, tinea capitis caused by fungal infection, hair loss caused by hypothyroidism or hyperthyroidism, hair loss caused by inflammation (seborrheic dermatitis), hair loss caused by malnutrition, hair loss caused by diabetes, hair loss caused by lupus, hair loss caused by hair growth disorders, hair loss caused by drug treatment (anticoagulants, antidepressants, discontinuation of oral contraceptives, chemotherapy), toxic folliculitis, lichen planopilaris, hair loss caused by burns or trauma, hair loss caused by ultraviolet radiation, and hair loss caused by exposure to fine dust in the air.

[0048] In embodiments, pharmaceutical compositions including the peptides of the present invention as active ingredients promote the proliferation of follicular dermal papillary cells (HFDPCs).

[0049] In embodiments, pharmaceutical compositions including the peptides of the present invention as active ingredients activate Akt or ERK proteins involved in signal transduction in follicular dermal papillary cells (HFDPCs).

[0050] In embodiments, pharmaceutical compositions comprising the peptides of the present invention as active ingredients activate β-catenin in follicular dermal papillary cells (HFDPCs) and promote its migration to the cell nucleus.

[0051] In embodiments, pharmaceutical compositions comprising the peptides of the present invention as active ingredients upregulate gene expression in follicular dermal papillary cells (HFDPCs) of one or more factors selected from the group consisting of LEF-1, c-Myc, and cyclin D1, which are downstream factors of β-catenin.

[0052] In embodiments, pharmaceutical compositions comprising the peptide of the present invention as an active ingredient downregulate the expression level of hair loss protein DKK-1 (Dickkopf-1) in follicular dermal papillary cells (HFDPC). Dihydrotestosterone (DHT) increases the expression level of hair loss protein DKK-1, and the peptide of the present invention downregulates the DKK-1 expression level increased by DHT.

[0053] In embodiments, pharmaceutical compositions comprising the peptides of the present invention as active ingredients increase gene expression of one or more proteins selected from the group consisting of Ha3-II, keratin 5, keratin 14, and keratin 19 in human hair follicle outer root sheath cells (HHORSC).

[0054] In embodiments, pharmaceutical compositions comprising the peptides of the present invention as active ingredients increase the expression of one or more transcription factors selected from the group consisting of MSX2, HOXC13 and FOXN1 in human hair follicle stromal cells (HHGMCs).

[0055] The pharmaceutical compositions of the present invention may include a therapeutically effective amount of the peptides of the present invention.

[0056] The term "therapeutic effective amount" refers to an amount sufficient to enable the peptide (the active ingredient of the pharmaceutical composition of the present invention) to achieve its activity or efficacy. For example, a therapeutic effective amount refers to a sufficient amount to achieve the efficacy of treating or preventing hair loss.

[0057] As used herein, the term “prevention” means reducing the risk of the development of a disease or disorder, and refers to any action that inhibits or delays the onset of a disease by preventing the progression of the disease or one or more of its clinical symptoms.

[0058] As used herein, the term “treatment” means to alleviate a disease or disorder and includes all actions that improve or beneficially alter the symptoms of a disease by halting or reducing the progression of the disease or one or more of its clinical symptoms.

[0059] In this invention, prevention or treatment of hair loss can be achieved by eliminating the cause of hair loss or inhibiting the progression of hair loss, or by promoting hair growth by inhibiting hair loss or promoting hair formation.

[0060] The pharmaceutical compositions of the present invention may include pharmaceutically acceptable carriers.

[0061] Pharmaceutically acceptable carriers commonly used in formulations include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylparaben, propylparaben, talc, magnesium stearate, mineral oil, etc.; however, carriers are not limited to these.

[0062] In addition to the above-mentioned components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc., but the components are not limited thereto.

[0063] Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington: The Science and Practice of Pharmacy (19th ed., 1995, Williams & Wilkins).

[0064] The pharmaceutical compositions of the present invention can be administered via any route suitable for treating hair loss (e.g., oral or parenteral). In the case of parenteral administration, the compositions can be administered via intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, topical application, or transdermal application. Because the pharmaceutical compositions of the present invention have activity in preventing or treating hair loss, they can be applied topically, such as by applying them to the scalp.

[0065] The dosage of the pharmaceutical composition may be from 0.0001 μg to 100 mg, 0.001 μg to 100 mg, 0.01 μg to 100 mg, 0.1 μg to 100 mg, or 1.0 μg to 1000 mg daily, but is not limited thereto. The pharmaceutical composition can be prescribed in various ways depending on factors such as preparation method, administration method, patient's age, weight, sex, pathological condition, food intake, time of administration, route of administration, excretion rate, and responsiveness.

[0066] The pharmaceutical compositions of the present invention can be formulated into unit dosage forms using pharmaceutically acceptable carriers and / or excipients according to methods readily practiced by those skilled in the art, or can be formulated by placing them in multi-dose containers. Specifically, the dosage form can be in the form of a solution, suspension, or emulsion in an oily or aqueous medium, or in the form of an extract, powder, granules, tablet, or capsule, and may additionally include dispersants or stabilizers.

[0067] The pharmaceutical compositions of the present invention can be topical skin preparations. Topical skin preparations are preparations that can be used by applying them to the external skin. When the pharmaceutical compositions of the present invention are used as topical skin preparations, they can be applied to the scalp, particularly to areas of hair loss or areas where hair growth is to be promoted. Topical skin preparations can be creams, gels, ointments, skin emulsifiers, skin suspensions, transdermal delivery patches, medicated bandages, lotions, or combinations thereof. Topical skin preparations can be appropriately mixed as needed with ingredients commonly used in topical skin preparations (e.g., cosmetics and pharmaceuticals), such as aqueous ingredients, oil-based ingredients, powdered ingredients, alcohols, moisturizers, thickeners, UV absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, various skin nutrients, or combinations thereof. Topical preparations may be appropriately mixed with metal chelating agents (such as disodium EDTA, trisodium EDTA, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, etc.), caffeine, tannins, herb extracts, glycyrrhizin, various herbs, drugs (such as tocopheryl acetate, glycyrrhizin, tranexamic acid and its derivatives or salts, etc.), vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, and sugars (such as glucose, fructose, trehalose, etc.).

[0068] In another aspect of the invention, the compositions of the invention provide cosmetic compositions for promoting hair growth or preventing or improving hair loss, the cosmetic compositions comprising: a peptide comprising the amino acid sequence of SEQ ID NO: 1 as an active ingredient.

[0069] As used herein, the term “improvement” refers to any action that improves or benefits the symptoms of a disease or disorder.

[0070] In embodiments, cosmetic compositions including the peptides of the present invention as active ingredients promote the proliferation of follicular dermal papillary cells (HFDPCs).

[0071] In embodiments, cosmetic compositions including the peptides of the present invention as active ingredients activate Akt or ERK proteins involved in signal transduction in follicular dermal papillary cells (HFDPCs).

[0072] In embodiments, cosmetic compositions including the peptides of the present invention as active ingredients activate β-catenin in follicular dermal papillary cells (HFDPCs) and promote its migration to the cell nucleus.

[0073] In embodiments, cosmetic compositions comprising the peptides of the present invention as active ingredients upregulate gene expression of one or more factors selected from the group consisting of LEF-1, c-Myc, and cyclin D1, which are downstream factors of β-catenin, in follicular dermal papillary cells (HFDPC).

[0074] In embodiments, cosmetic compositions comprising the peptide of the present invention as an active ingredient downregulate the expression level of DKK-1 (Dickkopf-1), a hair loss protein, in follicular dermal papillary cells (HFDPC). Dihydrotestosterone (DHT) increases the expression level of the hair loss protein DKK-1, and the peptide of the present invention downregulates the DKK-1 expression level increased by DHT.

[0075] In embodiments, cosmetic compositions including the peptides of the present invention as active ingredients increase gene expression of one or more proteins selected from the group consisting of Ha3-II, keratin 5, keratin 14 and keratin 19 in human hair follicle outer root sheath cells (HHORSC).

[0076] In embodiments, cosmetic compositions comprising the peptides of the present invention as active ingredients increase the expression of one or more transcription factors selected from the group consisting of MSX2, HOXC13 and FOXN1 in human hair follicle stromal cells (HHGMCs).

[0077] Cosmetic compositions can be formulated into any dosage form commonly prepared in the technical field to which this invention pertains, and can be topical skin preparations. For example, cosmetic compositions can be formulated as solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, sprays, etc., but are not limited thereto.

[0078] Cosmetic compositions can be formulated in various forms, such as solutions (e.g., softening lotions, nourishing lotions, nourishing creams, massage creams, serums, eye creams, cleansing creams, cleansing foams, cleansing waters, masks (packs), sprays, loose powders, hair tonics, hair creams, shampoos, hair dyes, conditioners, spray-type hairsprays, aerosol-type hairsprays, hair waxes, gels, etc.), sol-gels, emulsions, oils, waxes, aerosols, etc., but not limited to these.

[0079] The cosmetic compositions of the present invention may include other additives, such as excipients and carriers, and may be applied and mixed with commonly used ingredients in general skin cosmetics as needed.

[0080] When the dosage form of a cosmetic composition is a paste, cream, or gel, animal oils, vegetable oils, waxes, paraffin wax, starch, astragalus gum, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicon dioxide, talc, zinc oxide, etc., can be used as carrier ingredients.

[0081] When the cosmetic composition is in the form of a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component. Specifically, when the cosmetic composition is a spray, it may further include a propellant such as chlorofluorocarbon, propane / butane, or dimethyl ether, but is not limited thereto.

[0082] When the cosmetic composition is in the form of a solution or emulsion, solvents, solubilizers or emulsifiers may be used, and carrier ingredients may include, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol oil, glyceryl fatty acid esters, polyethylene glycol, and sorbitan fatty acid esters.

[0083] When the dosage form of a cosmetic composition is a suspension, liquid phase diluents (e.g., water, ethanol, and propylene glycol), suspending agents (e.g., ethoxyisostearyl alcohol, polyoxyethyl sorbitol ester, polyoxyethylene sorbitol ester, etc.), microcrystalline cellulose, aluminum hydroxide, bentonite, agar, astragalus gum, etc., can be used as carrier components.

[0084] When the dosage form of a cosmetic composition is a surfactant-containing cleanser, fatty alcohol sulfates / esters, fatty alcohol ether sulfates / esters, sulfosuccinate monoesters, hydroxyethyl sulfonates, imidazoline derivatives, methyl taurate / esters, sarcosinates / esters, fatty acid amide ether sulfates / esters, alkylamide betaine, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, etc., can be used as carrier components.

[0085] When the cosmetic composition is in the form of a shampoo, the peptides of the present invention can be mixed with basic ingredients used to form the shampoo, such as thickeners, surfactants, viscosity modifiers, humectants, pH adjusters, preservatives, and essential oils. CDE can be used as a thickener; LES (an anionic surfactant) and cocamidopropyl betaine (an amphoteric surfactant) can be used as surfactants; polyquaternium salts can be used as viscosity modifiers; glycerin can be used as a humectant; citric acid and sodium hydroxide can be used as pH adjusters. Grapefruit extract and the like can be used as preservatives; in addition, essential oils of cedarwood, peppermint, and rosemary, as well as amino acids, pentaol, or vitamin E can be added.

[0086] In addition to the peptides and carrier components of the present invention, the ingredients included in the cosmetic composition may include, but are not limited to, auxiliary ingredients commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances.

[0087] The peptides of the present invention can be included in the above compositions at concentrations from 0.01 μM to 1000 μM, and specifically, the peptides of the present invention can be in the following concentrations: 0.01 μM to 1000 μM; 0.05 μM to 800 μM, 0.05 μM to 700 μM, 0.05 μM to 600 μM, 0.05 μM to 500 μM, 0.05 μM to 300 μM, 0.05 μM to 200 μM; 0.1 μM to 800 μM, 0.1 μM to 700 μM, 0.1 μM to 600 μM, 0.1 μM to 500 μM, 0.1 μM to 300 μM, 0.1 μM to 200 μM; 0.3 μM to 800 μM, 0.3 μM to 700 μM, 0.3 μM to 600 μM, 0.3 μM to 500 μM. Concentrations of 0.3 μM to 300 μM, 0.3 μM to 200 μM; 0.3 μM to 150 μM, 0.3 μM to 100 μM, 0.3 μM to 90 μM, 0.3 μM to 80 μM, 0.3 μM to 70 μM or 0.3 μM to 60 μM are included in the above compositions; but are not limited thereto.

[0088] 3. Uses of the peptides of the present invention

[0089] In another aspect of the invention, a peptide comprising the amino acid sequence of SEQ ID NO: 1 is provided for use in promoting hair growth, or in inhibiting, preventing, treating or improving hair loss.

[0090] In another aspect of the invention, a method for promoting hair growth, or inhibiting, preventing, treating, or improving hair loss is provided, the method comprising administering to a subject who requires promotion of hair growth, or prevention, inhibition, treatment, or improvement of hair loss, a peptide comprising the amino acid sequence of SEQ ID NO: 1, or a composition comprising the peptide.

[0091] In another aspect of the invention, the use of a peptide comprising the amino acid sequence of SEQ ID NO: 1 is provided in the preparation of a medicament or cosmetic for promoting hair growth, or for preventing, treating or improving hair loss.

[0092] Beneficial effects

[0093] The peptides of this invention have the activity of promoting hair growth, or preventing, inhibiting or treating hair loss.

[0094] The peptides of this invention have the following effects: promoting the proliferation of human follicular dermal papillary cells (HFDPCs), activating cell proliferation-related signaling proteins Akt and ERK, activating β-catenin, enhancing the expression levels of downstream factors of β-catenin such as LEF-1, c-Myc, and cyclin D1, downregulating the expression level of the hair loss protein DKK-1, increasing the expression of keratin in outer root sheath cells (HORSCs), and increasing the expression of transcription factors involved in cell activation such as MSX2, HOXC13, and FOXN1 in germinal stromal cells (GMCs). The peptides of this invention can be used to promote hair growth, prevent or inhibit hair loss, or as active ingredients in therapeutic agents or cosmetics. Attached Figure Description

[0095] Figure 1 Experimental results show that when HHFDPC cells were treated with the peptides of the present invention at 500 nM, 5 μM and 50 μM, HHFDPC cell proliferation was promoted.

[0096] Figure 2 Experimental results show that when HHFDPC cells were treated with the peptides of the present invention at 500 nM, 5 μM, and 50 μM, phosphorylation of the cell proliferation-related signaling molecule Akt and extracellular regulated kinase (ERK) was increased.

[0097] Figure 3Experimental results show that when HHFDPC cells were treated with the peptides of the present invention at 500 nM, 5 μM, and 50 μM, β-catenin was activated and its migration to the cell nucleus was increased.

[0098] Figure 4 Experimental results show that when HHFDPC cells were treated with the peptides of the present invention at 500 nM, 5 μM, and 50 μM, the expression of LEF-1, a downstream factor of β-catenin, cyclin D1, and c-Myc was increased.

[0099] Figure 5 The results show that when HHFDPC cells were treated with the peptides of the present invention at 500 nM, 5 μM and 50 μM, the expression of DKK-1 (i.e., hair loss protein) induced by DHT treatment was reduced in a concentration-dependent manner.

[0100] Figure 6 Experimental results show that when HHORSC cells were treated with the peptides of the present invention at 500 nM, 5 μM and 50 μM, cell activity increased, thereby increasing the expression of cytokeratins (i.e. Ha3-II, keratin 5, keratin 14 and keratin 19).

[0101] Figure 7 Experimental results show that when HHGMC cells were treated with the peptides of the present invention at 500 nM, 5 μM and 50 μM, the expression of transcription factors (i.e. MSX2, HOXC13 and FOXN1, which are involved in cell activation) was increased. Detailed Implementation

[0102] The present invention will be described in detail below through embodiments. However, the following embodiments are for illustrative purposes only, and the scope of the present invention is not limited to these embodiments.

[0103] Preparation Example 1: Preparation of Peptides and Peptide Complexes

[0104] Peptides having the amino acid sequence SEQ ID NO: 1 shown in Table 1 were synthesized using an automated peptide synthesizer (Milligen 9050, Millipore, USA), and the synthesized peptides were purified using C18 reversed-phase high-performance liquid chromatography (HPLC) (Waters Associates, USA). The chromatographic column used was an ACQUITY UPLC BEH300 C18 (2.1 mm × 100 mm, 1.7 μm, Waters Co, USA).

[0105] [Table 1]

[0106]

[0107] The efficacy of the prepared peptide of SEQ ID NO: 1 was evaluated through the following experiments.

[0108] Experimental Example 1: Promoting the proliferation of human follicular dermal papillary cells (HHFDPC)

[0109] The effect of the peptide prepared in Preparation Example 1 above on the proliferation of human follicular dermal papillary cells (HHFDPC) was tested.

[0110] HHFDPC at 4×10 3 Cells were seeded at a density of 10 cells / well in 96-well cell culture plates and cultured for 24 hours in complete mesenchymal stem cell culture medium. The medium was then replaced with serum-free mesenchymal stem cell culture medium and cultured for another 24 hours. The cultured cell cultures were treated with peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM, respectively. Treatment with 1 μM VEGF served as a positive control, and no treatment was used as a negative control (con). These cultures were then cultured at 37°C for another 72 hours. Subsequently, 10 μL of 5 mg / mL MTT solution was added, and the mixture was incubated at 37°C in a CO2 incubator for 4 hours. The medium was then removed, and 100 μL of DMSO was added, followed by shaking for 10 minutes. Finally, the absorbance was measured at 540 nm using a spectrophotometer (Molecular Devices (SpectraMax iD3, CA, USA)).

[0111] Experimental results are as follows Figure 1 As shown, treatment of HHFDPC with the peptide from Preparation Example 1 at 500 nM, 5 μM, and 50 μM promoted HHFDPC proliferation compared to the negative control (con).

[0112] Experimental Example 2: Activation of proliferation-related signaling molecules in human dermal papillary cells of hair follicles

[0113] The effect of the peptide prepared in Example 1 above on the activation of proliferation-related signaling molecules in human follicular dermal papillary cells (HHFDPC) was confirmed by Western blot.

[0114] HHFDPC at 4×10 5Cells were seeded at a density of 10 cells / well in 6-well cell culture plates and cultured for 24 hours in complete mesenchymal stem cell medium. The medium was then replaced with serum-free mesenchymal stem cell medium and cultured for another 24 hours. Cultured cell cultures were treated with peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM, respectively. Treatment with 1 μM minoxidil (MNX) served as a positive control, and no treatment was used as a negative control (con). Cultures treated with these materials were then cultured at 37°C for another 24 hours. After washing each culture with PBS, cells were lysed with lysis buffer to obtain cell lysates. Equal volumes of protein samples were prepared by quantifying the cell lysates using BCA. The prepared protein samples were electrophoresed using 10% SDS-PAGE. The proteins separated by SDS-PAGE were transferred to a PVDF membrane and blocked with 5% skim milk at room temperature for 30 minutes. Anti-AKT and anti-ERK phosphate antibodies (CellSignaling, USA) were diluted 1:1000 in 3% BSA and reacted with the membrane at 4°C for 16 hours. The result was washed three times with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes each time. The secondary antibody was diluted 1:2000 in 5% skim milk and reacted at room temperature for 1 hour. The result was washed three times with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes each time, treated with ECL solution (GE Healthcare, USA), and detected using a membrane.

[0115] Experimental results are as follows Figure 2 As shown, treatment of HHFDPC with the peptides of Preparation Example 1 described above at 500 nM, 5 μM, and 50 μM resulted in increased phosphorylation of Akt and extracellular regulated kinase (ERK) (i.e., cell proliferation-related signaling molecules).

[0116] Experimental Example 3: Activation of β-catenin in human dermal papillary cells of hair follicles

[0117] The effect of the peptide prepared in Preparation Example 1 above on the activation of β-catenin in human follicular dermal papillary cells (HHFDPC) was confirmed by protein imprinting.

[0118] HHFDPC at 4×10 5Cells were seeded at a density of 10 cells / well in 6-well cell culture plates and cultured for 24 hours in complete mesenchymal stem cell medium. The medium was then replaced with serum-free mesenchymal stem cell medium and cultured for another 24 hours. Cultured cell cultures were treated with peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM, respectively. Treatment with 10 ng / mL rhWnt-3a (recombinant human Wnt-3a protein, R&D Systems (MN, USA)) served as a positive control, and no treatment was used as a negative control (con). Cultures treated with these materials were cultured at 37°C for another 24 hours. After washing each culture with PBS, nucleoproteins were isolated using a nucleoprotein extraction kit (Thermo Scientific, USA), and equal amounts of protein samples were prepared by BCA quantification. The prepared protein samples were electrophoresed using 10% SDS-PAGE. The proteins separated by SDS-PAGE were transferred to a PVDF membrane and blocked with 5% skim milk for 30 minutes at room temperature. Anti-β-catenin antibody (Cell Signaling, USA) and anti-HDAC1 antibody (Santa Cruz, USA) were diluted 1:1000 in 3% BSA and then reacted with the membrane at 4°C for 16 hours. The result was washed three times with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes each time. The secondary antibody was diluted 1:2000 in 5% skim milk and reacted at room temperature for 1 hour. The result was washed three times with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes each time, treated with ECL solution (GE Healthcare, USA), and detected using a membrane.

[0119] Experimental results are as follows Figure 3 As shown, it was confirmed that when HHFDPC was treated with the peptide of Preparation Example 1 at 500 nM, 5 μM and 50 μM, β-catenin was activated and its migration to the cell nucleus was increased.

[0120] Experiment Example 4: Promoting the expression of downstream genes of β-catenin in human dermal papilla cells

[0121] The effects of the peptides prepared in Example 1 above on the expression levels of lymphocyte enhancer-binding factor 1 (LEF-1), c-Myc, and cyclin D1, which are downstream genes of β-catenin, were determined by RT-PCR.

[0122] HHFDPC at 4×10 5Cells were seeded at a density of 10 cells / well in 6-well cell culture plates and cultured for 24 hours in complete mesenchymal stem cell medium. The medium was then replaced with serum-free mesenchymal stem cell medium and cultured for another 24 hours. Cultured cell cultures were treated with peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM, respectively. A positive control was obtained with 10 ng / mL rhWnt-3a (recombinant human Wnt-3a protein, R&D Systems (MN, USA)), and a negative control was obtained without any treatment. Each culture was then cultured at 37°C for another 24 hours. After washing each culture with PBS, RNA was isolated by treatment with 300 μL of eaay blue (Intron, South Korea). The isolated RNA was quantified using Nanodrop, and cDNA synthesis was performed using a cDNA synthesis kit (Enzynomics, South Korea). PCR reactions were then performed using a PCR premix (Enzynomics, South Korea) and the primers shown in Table 2 below. The PCR products were electrophoresed on a 1.5% agarose gel, and the bands were detected using the Bio-Rad gel imaging system.

[0123] [Table 2]

[0124]

[0125] Experimental results are as follows Figure 4 As shown, when HHFDPCs were treated with the peptides prepared in Example 1 above at 500 nM, 5 μM and 50 μM, β-catenin, which affects cell proliferation and differentiation, was activated, and the gene expression of its downstream factors (i.e. LEF-1, cyclin D1 and c-Myc) increased.

[0126] Experimental Example 5: Inhibition of the expression of the hair loss protein DKK-1 in human dermal papillary cells.

[0127] It is known that in hair follicles, dihydrotestosterone (DHT) promotes the expression of DKK-1 (Dickkopf-1), and DHT-induced DKK-1 inhibits the proliferation of keratinocytes in hair follicles and leads to their apoptosis, thereby promoting hair loss (J of InvestDermatolo. 2008, Feb., 128(2), pp. 262-269.).

[0128] The effect of the peptide prepared in Example 1 above on the expression level of the hair loss-inducing protein DKK-1 in human follicular dermal papillary cells (HHFDPC) was confirmed by Western blotting.

[0129] HHFDPC at 4×105 Cells were seeded at a density of 100 cells / well in 6-well cell culture plates and cultured for 24 hours in complete mesenchymal stem cell medium. The medium was then replaced with serum-free mesenchymal stem cell medium and cultured for another 24 hours. The cultured cell cultures were treated with peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM, respectively. Treatment with 5 μM finasteride served as a positive control, and no treatment was provided as a negative control (con). Specifically, DHT (an inducer of hair loss protein DKK-1) was simultaneously treated at a concentration of 100 nM. The cell cultures treated with the above materials were then cultured at 37°C for another 24 hours. After washing each culture with PBS, cells were lysed with lysis buffer to obtain cell lysates. Equal volumes of protein samples were prepared by quantifying the cell lysates using BCA. The prepared protein samples were electrophoresed using 10% SDS-PAGE. The proteins separated by SDS-PAGE were transferred to a PVDF membrane and blocked with 5% skim milk at room temperature for 30 minutes. Anti-DKK-1 antibody (Cell Signaling, USA) was diluted 1:1000 in 3% BSA and reacted with the membrane at 4°C for 16 hours. The result was washed three times with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes each time. The secondary antibody was diluted 1:2000 in 5% skim milk and reacted at room temperature for 1 hour. The result was washed three times with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes each time, treated with ECL solution (GE Healthcare, USA), and detected using a membrane.

[0130] like Figure 5 As shown, it was confirmed that when HHFDPC was treated with the peptide prepared in Example 1 above at concentrations of 500 nM, 5 μM and 50 μM, the expression of DKK-1 (hair loss protein) induced by DHT treatment decreased in a concentration-dependent manner.

[0131] Experimental Example 6: Activation of Human Hair Outer Root Sheath Cells (HHORSC)

[0132] The effect of the peptide prepared in Preparation Example 1 above on the activation of human hair outer root sheath cells (HHORSC) was confirmed by measuring the gene expression of cytokeratin.

[0133] HHORSC at 4×10 3Cells were seeded at a density of 100 cells / well in 96-well cell culture plates and cultured for 24 hours in complete mesenchymal stem cell medium. The medium was then replaced with serum-free mesenchymal stem cell medium and cultured for another 24 hours. Cultured cell cultures were treated with the peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM, respectively. Treatment with 100 nM epidermal growth factor (EGF) served as a positive control, and no treatment was used as a negative control (con). These cultures were then cultured at 37°C for another 24 hours. After washing each culture with PBS, RNA was isolated by treatment with 300 μL of eaay blue (Intron, South Korea). The isolated RNA was quantified using a nanodrop, and cDNA synthesis was performed using a cDNA synthesis kit (Enzynomics, South Korea). PCR reactions were then performed using a PCR premix (Enzynomics, South Korea) and the primers shown in Table 3 below. The PCR products were electrophoresed on a 1.5% agarose gel, and the bands were detected using the Bio-Rad gel imaging system.

[0134] [Table 3]

[0135]

[0136] Experimental results are as follows Figure 6 As shown, it was confirmed that when HHORSCs were treated with the peptides of Preparation Example 1 above at 500 nM, 5 μM and 50 μM, their cell activity increased, thereby increasing the expression of all Ha3-II, keratin 5, keratin 14 and keratin 19 (i.e., cytokeratins that function to form the cytoskeleton and constitute hair).

[0137] Experimental Example 7: Activation of Human Hair Growth Stromal Cells (HHGMCs)

[0138] The effect of the peptide prepared in Preparation Example 1 above on the activation of human hair growth stromal cells (HHGMCs) was confirmed by measuring the expression of MSX2, HOXC13 (Homeobox C13), and FOXN1 (Forkhead Box N1), transcription factors associated with cell activation.

[0139] HHGMC at 4×10 5Cells were seeded at a density of 10 cells / well in 6-well cell culture plates and cultured for 24 hours in complete mesenchymal stem cell medium. The medium was then replaced with serum-free mesenchymal stem cell medium and cultured for another 24 hours. Cultured cell cultures were treated with the peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM, respectively. Treatment with 100 nM epidermal growth factor (EGF) served as a positive control, and no treatment was used as a negative control (con). These cultures were cultured at 37°C for 24 hours. After washing each culture with PBS, RNA was isolated by treatment with 300 μL of eaay blue (Intron, South Korea). The isolated RNA was quantified using a nanodrop, and cDNA synthesis was performed using a cDNA synthesis kit (Enzynomics, South Korea). PCR reactions were then performed using a PCR premix (Enzynomics, South Korea) and the primers shown in Table 4 below. The PCR products were electrophoresed on a 1.5% agarose gel, and the bands were detected using the Bio-Rad gel imaging system.

[0140] [Table 4]

[0141]

[0142] Experimental results are as follows Figure 7 As shown, treatment of HHGMCs with the peptides prepared in Example 1 above at 500 nM, 5 μM, and 50 μM increased the expression of transcription factors MSX2, HOXC13, and FOXN1, which are involved in cell activation.

[0143] Preparation Example 2: Preparation of Pharmaceutical Compositions

[0144] 2-1. Preparation of Powder

[0145] The peptide 2 g of the present invention

[0146] 1 g of lactose

[0147] The above ingredients are mixed and then filled into an airtight bubble to prepare a powder.

[0148] 2-2. Tablet Preparation

[0149] The peptide of this invention, 100 mg

[0150] 100 mg of corn starch

[0151] Lactose 100 mg

[0152] Magnesium stearate 2 mg

[0153] The above ingredients are mixed and prepared into tablets by compression according to conventional tablet preparation methods.

[0154] 2-3. Capsule Preparation

[0155] The peptide of this invention, 100 mg

[0156] 100 mg of corn starch

[0157] Lactose 100 mg

[0158] Magnesium stearate 2 mg

[0159] The above ingredients are mixed and then filled into each gelatin capsule according to conventional capsule preparation methods to prepare capsules.

[0160] 2-4. Preparation of pills

[0161] The peptide 1 g of the present invention

[0162] 1.5 g lactose

[0163] 1 g of glycerin

[0164] Xylitol 0.5 g

[0165] After mixing the above ingredients, the mixture is prepared into pills at a dosage of 4 g per pill according to conventional methods.

[0166] 2-5. Preparation of Granules

[0167] The peptide of this invention, 150 mg

[0168] Soybean extract 50 mg

[0169] 200 mg glucose

[0170] Starch 600 mg

[0171] The above ingredients are mixed, and 100 mg of 30% ethanol is added. The mixture is dried at 60°C to form granules, which are then filled into bags.

[0172] Preparation Example 3: Preparation of Cosmetic Compositions

[0173] 3-1. Preparation of Cream

[0174] The peptide of this invention: 4.6 parts by weight

[0175] Cetearyl alcohol: 2.8 parts by weight

[0176] Beeswax: 2.6 parts by weight

[0177] Stearic acid: 1.4 parts by weight

[0178] Lipophilic glyceryl monostearate: 2 parts by weight

[0179] PEG-100 stearate: 1 part by weight

[0180] Sorbitol sesquioleate: 1.4 parts by weight

[0181] Jojoba oil: 4 parts by weight

[0182] Squalene: 3.8 parts by weight

[0183] Polysorbate 60: 1.1 parts by weight

[0184] Macadamia nut oil: 2 parts by weight

[0185] Tocopherol acetate: 0.2 parts by weight

[0186] Methyl polysiloxane: 0.4 parts by weight

[0187] Ethyl paraben: 0.1 parts by weight

[0188] Propylparaben: 0.1 parts by weight

[0189] Euxyl K-400: 0.1 parts by weight

[0190] 1,3-Butanediol: 7 parts by weight

[0191] Methylparaben: 0.05 parts by weight

[0192] Glycerin: 6 parts by weight

[0193] d-Panthenol: 0.2 parts by weight

[0194] Triethanolamine: 0.2 parts by weight

[0195] pt 41891: 0.2 parts by weight

[0196] p-H2O: 46.05 parts by weight

[0197] 3-2. Preparation of the detergent

[0198] The peptide of this invention: 3.5 parts by weight

[0199] Cetearyl alcohol: 1.6 parts by weight

[0200] Stearic acid: 1.4 parts by weight

[0201] Lipophilic glyceryl monostearate: 1.8 parts by weight

[0202] PEG-100 stearate: 2.6 parts by weight

[0203] Sorbitol sesquioleate: 0.6 parts by weight

[0204] Squalene: 4.8 parts by weight

[0205] Macadamia nut oil: 2 parts by weight

[0206] Jojoba oil: 2 parts by weight

[0207] Tocopheryl acetate: 0.4 parts by weight

[0208] Methyl polysiloxane: 0.2 parts by weight

[0209] Ethyl paraben: 0.1 parts by weight

[0210] Propylparaben: 0.1 parts by weight

[0211] 1,3-Butanediol: 4 parts by weight

[0212] Methylparaben: 0.1 parts by weight

[0213] Xanthan gum: 0.1 parts by weight

[0214] Glycerin: 4 parts by weight

[0215] d-Panthenol: 0.15 parts by weight

[0216] Allantoin: 0.1 parts by weight

[0217] Calcium carbonate (2% aq. Sol): 4 parts by weight

[0218] Triethanolamine: 0.15 parts by weight

[0219] Ethanol: 3 parts by weight

[0220] pt 41891: 0.1 parts by weight

[0221] p-H2O: 48.3 parts by weight

[0222] 3-3. Preparation of softening toner

[0223] The peptide of this invention is 0.2 wt%.

[0224] 10.0 wt% ethanol

[0225] Polyoxyethylene dehydrated sorbitol polylaurate 1.0 wt%

[0226] Methylparaben 0.2 wt%

[0227] Glycerin 5.0 wt%

[0228] 1,3-Butanediol 6.0 wt%

[0229] Spices as needed

[0230] Pigment in appropriate amount

[0231] Appropriate amount of purified water

[0232] Total 100

[0233] 3-4. Preparation of Nourishing Toner

[0234] The peptide of this invention is 0.1 wt%.

[0235] Vaseline 2.0 wt%

[0236] 0.8 wt% of dehydrated sorbitan sesquioleate

[0237] Polyoxyethylene oleyl ethyl ether 1.2 wt%

[0238] Appropriate amount of methylparaben

[0239] Propylene glycol 5.0 wt%

[0240] 3.2 wt% ethanol

[0241] Polyvinyl carboxylate 18.0 wt%

[0242] Pigment in appropriate amount

[0243] Spices as needed

[0244] Appropriate amount of purified water

[0245] Total 100

[0246] 3-5. Preparation of the serum

[0247] The peptide of this invention is 5.0 wt%.

[0248] Propylene glycol 10.0 wt%

[0249] Glycerin 10.0 wt%

[0250] Aqueous solution of sodium hyaluronate (1%) 5.0 wt%

[0251] 3.2 wt% ethanol

[0252] Polyoxyethylene hydrogenated castor oil 1.0 wt%

[0253] Methylparaben 0.1 wt%

[0254] Spices as needed

[0255] Appropriate amount of purified water

[0256] Total 100

[0257] 3-6. Preparation of Facial Masks

[0258] The peptide of this invention is 0.5 wt%.

[0259] Glycerin 5.0 wt%

[0260] Propylene glycol 4.0 wt%

[0261] Polyvinyl alcohol 15.0 wt%

[0262] 8.0 wt% ethanol

[0263] Polyoxyethylene oil-based ether 1.0 wt%

[0264] Methylparaben 0.2 wt%

[0265] Spices as needed

[0266] Pigment in appropriate amount

[0267] Appropriate amount of purified water

[0268] Total 100

[0269] In a preferred embodiment, the composition described above is a mixture of suitable ingredients, but its composition or mixing ratio can be arbitrarily modified according to regional or ethnic preferences (such as demand segments, national needs, and intended use).

[0270] The foregoing has described representative embodiments of this application by way of exemplary implementation; however, the scope of this application is not limited to the specific embodiments described above, and those skilled in the art can make appropriate modifications within the scope of the claims of this application.

Claims

1. A peptide consisting of the amino acid sequence of SEQ ID NO:

1.

2. A composition for promoting hair growth or preventing or improving hair loss, said composition comprising the peptide of claim 1 as an active ingredient.

3. A pharmaceutical composition for the prevention or treatment of hair loss, said pharmaceutical composition comprising the peptide of claim 1 as an active ingredient.

4. The pharmaceutical composition according to claim 3, wherein, The pharmaceutical composition is a topical skin preparation.

5. Use of the peptide of claim 1 in the preparation of a pharmaceutical composition for the prevention or treatment of hair loss, wherein, The peptide promotes the proliferation of dermal papillary cells in hair follicles.

6. The use according to claim 5, wherein, The peptide: (i) Activation of Akt or ERK signaling proteins in the dermal papilla cells of the hair follicle; or (ii) β-catenin is activated in the dermal papilla cells of the hair follicle.

7. The use according to claim 5, wherein, In the dermal papilla cells of the hair follicle, the peptide upregulates the gene expression of one or more factors selected from the group consisting of LEF-1, c-Myc, and cyclin D1, wherein LEF-1, c-Myc, and cyclin D1 are downstream factors of β-catenin.

8. The use according to claim 5, wherein, In the dermal papilla cells of the hair follicle, the peptide downregulates the expression level of the hair loss protein DKK-1.

9. The use according to claim 5, wherein, In the outer root sheath cells of hair follicles, the peptide increases the expression of one or more proteins selected from the group consisting of Ha3-II, keratin 5, keratin 14, and keratin 19.

10. The use according to claim 5, wherein, In germinal stromal cells, the peptide increases the expression of one or more transcription factors selected from the group consisting of MSX2, HOXC13, and FOXN1.

11. A cosmetic composition for promoting hair growth or preventing or improving hair loss, said cosmetic composition comprising the peptide of claim 1 as an active ingredient.

12. The cosmetic composition according to claim 11, wherein, The cosmetic composition is a topical skin preparation.

13. The cosmetic composition according to claim 11, wherein, The cosmetic composition is one or more dosage forms selected from the group consisting of solutions, suspensions, emulsions, pastes, gels, creams, powders, surfactant-containing detergents, oils, and sprays.

14. The cosmetic composition according to claim 11, wherein, The cosmetic composition is one or more dosage forms selected from the group consisting of lotions, soaps, powder foundations, emulsion foundations, and wax foundations.

15. The cosmetic composition according to claim 11, wherein, The cosmetic composition is one or more formulations selected from the group consisting of hair conditioner, hair cream, shampoo, hair dye, spray hairspray, aerosol hairspray, hair wax, and gel.

16. The cosmetic composition according to claim 11, wherein, The cosmetic composition is one or more formulations selected from the group consisting of conditioner and shampoo.

17. Use of the peptide of claim 1 in the preparation of a cosmetic composition for promoting hair growth or preventing or improving hair loss, wherein, The peptide promotes the proliferation of dermal papillary cells in hair follicles.

18. The use according to claim 17, wherein, The peptide: (i) Activation of Akt or ERK signaling proteins in the dermal papilla cells of the hair follicle; or (ii) β-catenin is activated in the dermal papilla cells of the hair follicle.

19. The use according to claim 17, wherein, In the dermal papillary cells of the hair follicle, the peptide upregulates the gene expression of one or more factors selected from the group consisting of LEF-1, c-Myc, and cyclin D1, wherein LEF-1, c-Myc, and cyclin D1 are downstream factors of β-catenin.

20. The use according to claim 17, wherein, In the dermal papilla cells of the hair follicle, the peptide downregulates the expression level of the hair loss protein DKK-1.

21. The use according to claim 17, wherein, In the outer root sheath cells of hair follicles, the peptide increases the expression of one or more proteins selected from the group consisting of Ha3-II, keratin 5, keratin 14, and keratin 19.

22. The use according to claim 17, wherein, In germinal stromal cells, the peptide increases the expression of one or more transcription factors selected from the group consisting of MSX2, HOXC13, and FOXN1.

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