OA19189A - Conjugate of Minoxidil and Peptide. - Google Patents

Abstract

The present invention relates to a composition for preventing hair loss and, more specif ically, to a compound having a structure in which Minoxidil and a peptide are chemically connected, and to a pharmaceutical composition or cosmetic composition for preventing hair loss or promoting hair growth comprising the compound. The compound having a structure in which Minoxidil and a peptide are chemically connected according to the present invention has not only excellent physiological activity such as hair loss reduction, hair growth promotion or cell growth promotion, but also excellent stability in water, and can therefore be useful as a composition for preventing hair loss and promoting hair growth.

Description

[description]

[invention Title]

CONJUGATE OF MINOXIDIL AND PEPTIDE

[Technical Field]

The présent invention relates to a conjugate of

Minoxidil and peptide, and more particularly, to a conjugate of Minoxidil and peptide in which each activity synergizes with each other while retaining the respective properties of Minoxidil and peptide.

[Background Art]

A hair follicle is a unique organ of mammalian skin, which is formed by growing and extending of the lower part of the primitive epidermis into a deeper skin layer. The plug of cells known as saccule or dermal papilla exists in 15 the base of the hair follicle, and papilla is essential in normal circulation of the hair follicle and in growth of the hair shaft. The hair shaft has a thread-shaped structure formed by épithélial cells that are composed of keratin filaments and filament-aggregating proteins tightly attached thereto.

Human hair periodically repeats anagen, catagen, and telogen phases, and goes through the process of hair loss and régénération. The hair cycle is determined by hormone régulation and many growth factors, and hair enters the 25 telogen phase early through the catagen phase by severe stress or malnutrition and causes severe hair loss symptoms.

The loss phenomenon of haïr from the scalp is called hair loss, and factors affecting hair loss may include environmental factors such as climate, exposure to light or heat, and internai factors such as disease, birth, hormone sécrétion and changes, drug use, and nutritional status. Hair loss can also be caused by lack of nutrition, scalp drying, stress, etc. in addition to enzymatic action. In the case of hair loss due to such causes, hair loss can be prevented by sufficient nutrition supply, scalp management and ingestion or administration of antioxidants while hair growth can be promoted.

In order to treat such hair loss phenomenon, various materials hâve been used as medicines until now, but they had the disadvantage that the price was too expensive or the individual différences in efficacy were too high. For other cosmetic products, they hâve used botanical extracts which are cheaper but hâve little effect, and thus the effect was insignif icant. A typical example of a drug used for hair loss is Minoxidil. The Minoxidil has been approved by the US FDA and has been reported to hâve an activity of inducing the anagen phase from the hair cycle of the telogen phase and maintaining the hair cycle of the induced anagen phase, besides the vasodilator function as a unique potassium channel opener. However, the Minoxidil may, when used, delay hair loss, but could not actually be used to induce régénérât ion of new hair follicles. In addition, the

Minoxidil has a low solubility in water and thus is precipitated and is difficult to use. To solve these problems, Patent Document 1 (Korean Laid-open Patent Publication No. 10-2012-0011632) discloses a technique of adding a surfactant when using the Minoxidil.

Meanwhile, there are many factors linked to each other in the process of hair growth and degeneration. For example, a study has been reported using a sériés of growth factors to promote hair growth by promoting the growth factor of the 10 kératinocyte, promoting the activity of the vascular endothélial growth factor, promoting the WINT pathway, and inhibiting the activity of proteins involved in the BMP pathway. However, the growth factors are highly effective, but require additional processing and time for refolding to 15 obtain a natural growth factor, and also require a complex purification process to remove contaminants from E. coli during the purification process, and is less useful because of its stability and its high molecular weight and thus its inability to easily jump over the hair's protective membrane 20 in combination with high price.

Accordingly, the inventors of the présent invention hâve developed peptides that can perform the same or similar functions or actions as natural growth factors, but hâve better- stability than the natural growth factors and can 25 overcome problems caused by the large molecular weight of the natural growth factors, that is, a Nokkin peptide composed of the amino acid sequence of SEQ ID NO: 3 (Patent Document 2: Korean Laid-open Patent Publication No. 10-20100085407), a Keramin2 peptide composed of the amino acid sequence of SEQ ID NO: 2 (Patent Document 3: Korean Laidopen Patent Publication No. 10-2009-0108323) and a WINT peptide composed of the amino acid sequence of SEQ ID NO: 1 (Patent Document 4: Korean Laid-open Patent Publication No. 10-2011-0023991) .

However, conventionally used Minoxidil or peptides consisting of the amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 3 still need to be improved in terms of preventing hair loss and improving hair growth promoting performance, reducing side effects, and increasing solubility in water.

To solve these problems, the inventors of the présent invention hâve prepared Minoxidil-Nokkin, Minoxidil—Keramin 2 and Minoxidil-WINT peptides by chemically conjugating Minoxidil to the peptides consisting of the amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 3, respectively and hâve confirmed that the compounds promote the activity of the vascular endothélial growth factor associated with hair growth, promote the WINT pathway, and inhibit the activity of proteins involved in hair loss in the major BMP pathway, thereby completing the présent invention.

[Disclosure]

[Technical Problem]

The présent invention is to solve the problems of the conventional hair growth solution, and thus it is a technical object of the présent invention to provide a material having superior physiological properties such as stability to water while having the same or superior hair loss prévention and/or hair growth promoting function, as compared to the conventional hair growth solutions such as natural growth factors, peptides consisting of amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 3, or the Minoxidil.

[Technical Solution]

In order to achieve the above object, the présent invention provides a compound having a structure in which the Minoxidil and peptide are chemically bonded.

According to one embodiment of the présent invention, the peptide may be composed of 2 to 30, preferably 5 to 20, more preferably 8 to 15, and more preferably 10 to 12 amino acid sequences, but is not limited thereto.

According to another embodiment of the présent invention, the peptide is preferably a water-soluble peptide, but is not limited thereto. According to a preferred embodiment of the présent invention, the watersoluble peptide has preferably the ratio of hydrophilic side chain-containing amino acids of no less than 50%, preferably no less than 60%, more preferably no less than 70%, more preferably no less than 80%, more preferably no less than 90% and most preferably 100%. According to another preferred embodiment of the présent invention, the water-soluble peptide has preferably no more than 5 amino acids, preferably no more than 4 amino acids, more preferably no more than 3 amino acids, more preferably no more than 2 amino acids, more preferably no more than 1 amino acid, which hâve hydrophilic side chains, and most preferably has no amino acid.

According to another embodiment of the présent invention, the peptide may be, but is not limited to, a Nokkin peptide consisting of the amino acid sequence of SEQ ID NO: 1; a Keramin2 peptide consisting of the amino acid sequence of SEQ ID NO: 2; or a WINT peptide consisting of the amino acid sequence of SEQ ID NO: 3.

In addition, the présent invention provides a pharmaceutical composition for hair loss prévention or hair growth promotion comprising any one of the compounds disclosed above.

In addition, the présent invention provides a cosmetic composition for hair loss prévention or hair growth promotion comprising any one of the compounds disclosed above.

According to one embodiment of the présent invention, the cosmetic composition may be, but is not limited to, formulations such as emollient beauty wash, nutrition beauty wash, nutrition creams, massage creams, essences, eye creams, cleansing creams, cleansing foams, cleansing water, packs, spray, powders, hair tonie, hair creams, hair lotions, hair shampoo, hair rinses, hair conditioners, hair spray, hair air-sol, pomades, sol-gel, émulsions, oils, waxes, or air-sol.

[Advantageous Effects]

The compounds according to the présent invention, which hâve the structure which the Minoxidil and the peptide are chemically bonded, hâve excellent physiological activity such as improvement of hair loss, hair growth promotion and cell growth promotion, and also has excellent stability in water and skin perméation rate, and thus can be useful as a composition for hair loss réduction and hair growth promotion.

However, the effects of the présent limited to the above-mentioned effects, and other effects not mentioned can be clearly understood by those skilled in the art from the following description.

[Description of Drawings]

FIG. 1 is a photograph showing the solubility in water of the compound of the présent invention and the Minoxidil.

FIG. 2 a graph showing the degree of of human umbilical endothélial cells (HUVEC) when treated with the compound of the présent invention.

FIG. 3 graph showing the degree of human hair dermal papilla cells (HHDPC) when treated with the compound of the présent invention.

FIGs. 4 to 6 show the results of confirming the amount of mRNA of VEGF and TGFpl when treated with the compound of the présent invention.

FIG. 7 shows the resuit of confirming the amount of VEGF protein when treated with the compound of the présent invention.

FIGs. 8 and 9 are images showing the degree of blood vessel formation when treated with the compound of the présent invention.

FIGs. 10 and 11 show the results of confirming the effect of the compound of the présent invention on nucléus translocation of β-catenin, which is a signal pathway of WINT.

FIGs. 12 and 13 show the results of confirming whether the compound of the présent invention inhibits the BMP signal pathway which is a major factor of hair loss, by the inhibition of phospho-Smadl/5/8 activation (migration from the cytoplasm to the nucléus).

FIGs. 14 and 15 are results of confirming the degree of hair growth when treated with the compound of the présent invention.

[Best Mode]

In order to achieve the above object, the présent invention provides a compound having a structure in which the Minoxidil and peptide are chemically bonded.

The Minoxidil is 6-amino-l,2-dihydro-l-hydroxy-2-imino-

4-phenoxypyrimidine having a structure represented by the following formula 1 :

[Formula 1]

Hereinafter, the présent invention will be described in detail.

The term peptide as used herein refers to a linear molécule formed by amino acid residues joined together by a peptide bond. The peptide can be prepared according to conventional biological or chemical synthesis methods known in the art, particularly solid-phase synthesis techniques (Merrifield, J. Amer. Chem. Soc., 85:2149-54(1963)).

The peptide is intended to increase the water solubility of the Minoxidil. In this respect, the peptide is preferably a water-soluble peptide, but is not limited thereto. According to one embodiment of the présent invention, the peptide is composed of 2 to 30, preferably 5 to 20, more preferably 8 to 15, and more preferably 10 to 12 amino acid sequences. According to a preferred embodiment of the présent invention, the peptide has preferably the ratio of hydrophilic side chain-containing amino acids of no less than 50%, preferably no less than 60%, more preferably no

ΙΟ less than 70%, more preferably no less than 80%, more preferably no less than 90% and most preferably 100%. On the other hand, the peptide has the ratio of hydrophobie side chain-containing amino acid of less than 50%, preferably no more than 40%, more preferably no more than 30%, more

preferably no	more than 20%,	more	preferably no more	than
10% and most	preferably 0%.	The	term	hydrophilic	side
chain-containing amino acid	as	used	herein refers	to

arginine (Arg), histidine (His), lysine (Lys), asparaginic acid (Asp), glutamic acid (Glu), serine (Ser), threonine (Thr), asparagine (Asn), glutamine (Gin), cysteine (Cys), selenocysteine (Sec), glycine (Gly) and proline (Pro) and the term hydrophobie side chain-containing amino acid refers to alanine (Ala), valine (Val), isoleucine (Ile), leucine (Leu), méthionine (Met), phenylalanine (Phe), tyrosine (Tyr) and tryptophan(Trp), but is not limited thereto, and in addition to the above-mentioned amino acids présent in nature, modified products thereof and the like can be also used without limitation. According to a preferred embodiment of the présent invention, the hydrophobie side chain-containing amino acid is présent in the peptide in an amount of not more than 5, preferably not more than 4, more preferably not more than 3, more preferably not more than 2, more preferably not more than 1, and most preferably 0. According to one embodiment of the présent invention, the peptide is préférable, but is not limited to, a Nokkin peptide consisting of the amino acid sequence of SEQ ID NO: 1; a Keramin2 peptide consisting of the amino acid sequence of SEQ ID NO: 2; and a WINT peptide consisting of the amino acid sequence of SEQ ID NO: 3.

According to one embodiment of the présent invention, the compound of the présent invention has cell growth promoting ability with regard to human umbilical vein endothélial cells (HUVEC) and human hair dermal papilla cells (HHDPC). According to another embodiment of the présent invention, the compound of the présent invention has a function of activating the WNT signal transduction pathway. According to another embodiment of the présent invention, the compound of the présent invention transfers the β-catenin into the nucléus. According to another embodiment of the présent invention, the compound of the présent invention blocks the BMP signal pathway, which is a major factor of hair loss.

The compound of the présent invention has excellent stability by itself, but the stability can be further improved by modifying any amino acid constituting the peptide bound to the compound. According to one embodiment of the présent invention, the N-terminal of the peptide can bind with a protecting group selected from the group consisting of acetyl group, fluorenyl methoxy carbonyl group, formyl group, palmitoyl group, myristyl group, stearyl group and polyethylene glycol (PEG), and thus the stability can be further improved. According to another embodiment of the présent invention, the peptide can bind with a protecting group selected from the group consisting of acetyl group, fluorenyl methoxy carbonyl group, formyl group, palmitoyl group, myristyl group, stearyl group and polyethylene glycol (PEG), and thus the stability can be further improved.

Modifications of the amino acids as described above play a rôle in greatly improving the stability of the compounds of the présent invention. The term stability as used herein is intended to encompass in vitro stability as well as in vivo stability such as storage stability (e.g., room température storage stability). In addition, the abovementioned protecting group plays a rôle of protecting the compound of the présent invention from attack of protease in vivo and in vitro.

In addition, the présent invention provides a composition for treating or ameliorating hair loss comprising the compound as an effective component. According to another embodiment of the présent invention, the présent invention provides a composition for improving skin condition comprising the peptide as an effective component. In the présent invention, the composition may be in the form of a pharmaceutical composition or health food, but is not limited thereto.

Since the composition of the présent invention comprises the aforementioned compound of the présent invention as an effective component, the contents common to both of them are omitted in order to avoid the excessive complexity of the présent spécification.

According to one embodiment of the présent invention, the treatment or amelioration of hair loss by the compounds of the présent invention is hair growth promotion or hair production. According to a preferred embodiment of the présent invention, the compound of the présent invention has HUVEC and HHDPC cell growth promotion ability, and promûtes the β-catenin signal transduction pathway, a typical signal transduction pathway of WINT protein. According to another embodiment of the présent invention, the compound of the présent invention blocks the BMP signal pathway, which is a major factor of hair loss. Animal experiments based on these results showed that the compound of the présent invention significantly promoted hair growth. Therefore, the composition of the présent invention is very effective in improving hair growth and skin condition.

Also, according to one embodiment of the présent invention, the improvements in skin condition by the compound of the présent invention are improvement in wrinkles, improvement in skin elasticity, prévention of skin aging, improvement in skin moisturizing, treatment of wounds, or skin régénération.

Since the composition of the présent invention comprises the aforementioned compound of the présent invention as an effective component, the content common to both of them is omitted in order to avoid the excessive complexity of the présent spécification.

According to a preferred embodiment of the présent invention, the composition of the présent invention is a pharmaceutical composition comprising (a) a pharmaceutically effective amount of the aforementioned compound of the présent invention and (b) a pharmaceutically acceptable carrier.

The term pharmaceutically effective amount as used herein refers to an amount sufficient to achieve efficacy or activity of the compound of the présent invention described above.

The pharmaceutically acceptable carriers contained in the pharmaceutical composition of the présent invention include those conventionally used in the préparation of formulations, and include for example, but is not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnésium stéarate, minerai oils and the like. The pharmaceutical composition of the présent invention may further include lubricants, wetting agents, sweetening agents, flavoring agents, emulsifying agent, suspending agents, preservatives and the like in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Korean Laid-open Patent Publication No. 2017-0027312.

The pharmaceutical composition of the présent invention can be prepared by formulating as a unit dosage form or by inserting into a multi-dose container using pharmaceutically acceptable carriers and/or excipients, according to a method which can be easily carried out by a person having ordinary skill in the art to which the présent invention pertains. In this case, the formulations may be in the form of solutions, suspensions or émulsions in oil or aqueous media, or may be in the form of extracts, powders, granules, tablets, capsules or gels (e.g., hydrogels), and may additionally include dispersing agents or stabilizers.

The pharmaceutical composition according to the présent invention can be administered orally or parenterally at the time of clinical administration and can be used in the form of a general pharmaceutical préparation. That is, the pharmaceutical composition of the présent invention can be administered orally or parenterally as various clinical formulations at the time of actually clinical administration, and when the pharmaceutical composition of the présent invention is formulated, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants which are usually used. Solid formations for oral administration may include tablets, pills, powders, granules or capsules, and the solid formations may be prepared by mixing a herbal extract or a fermented herbal extract with one or more excipients such as starch, calcium carbonate, sucrose, lactose or gelatin. In addition to the simple excipients, lubricants such as magnésium stéarate and talc are also used. Liquid formations for oral administration, comprising

suspension, liquid for	internai	use,	émulsion,	syrup, etc.,
may include simple	diluents	such	as	water	or liquid
paraffin, as well as	various	excipients	such	as wetting

agents, sweeting agents, fragrance, or preservatives. Formulations for parentéral administration may include sterilized aqueous solution, nonaqueous solvent, suspending agent, émulsion, freeze drying agent or suppository. Nonaqueous solution and suspension may be propylene glycol, polyethylene glycol, vegetable oil such as olive oil, ester available for injection such as ethyl oleate. The base of suppository may be witepsol, macrogol, tween 61, cacao oil, laurin oil, glycerol, gelatin and the like.

Dosage units may contain, for example, 1, 2, 3 or 4 times, or 1/2, 1/3 or 1/4 times the individual dosage. Individual dosage will contain the amount of the active drug which is administered in a single dose, and usually correspond to ail, one-half, one-third, or one-fourth of the daily dose.

The pharmaceutical composition of the présent invention can be prepared by formulating as a unit dosage form or by inserting into a multi-dose container using pharmaceutically acceptable carriers and/or excipients, according to a method which can be easily carried out by a person having ordinary skill in the art to which the présent invention pertains. In this case, the formulations may be in the form of solutions, suspensions or émulsions in oil or aqueous media, or may be in the form of extracts, powders, granules, tablets, capsules or gels (e.g., hydrogels), and may additionally include dispersing agents or stabilizers.

According to a preferred embodiment of the présent invention, the composition of the présent invention is a cosmetic composition comprising (a) a cosmetically effective amount of the compound of the présent invention as described above; and (b) a cosmetically acceptable carrier.

The term cosmetically effective amount as used herein refers to the amount of the composition of the présent invention described above sufficient to achieve a skin condition-improving effect.

The cosmetic compositions of the présent invention may be prepared as any formulation conventionally produced in the art, for example, including solutions, suspensions, émulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, émulsion foundations, wax foundations and sprays, but are not limited thereto. More specifically, the cosmetic compositions of the présent invention may be prepared in various forms, for example, solutions, sol-gels, émulsions, oils, waxes, air-sols and the like, such as emollient beauty wash, nutrition beauty wash, nutrition creams, massage creams, essences, eye creams, cleansing creams, cleansing foams, cleansing water, packs, sprays, powders, hair tonie, hair creams, hair lotions, hair shampoo, hair rinses, hair conditioners, hair-sprays, hair air-sols, pomades, and gels, but are not limited thereto.

The paste, cream or gel formulations of the présent invention may include animal oils, plant oils, waxes, paraffin, starch, tragacanth, cellulose dérivâtes, polyethylene glycol, silicon, bentonite, silica, talc or zinc oxide as a carrier component.

The powder or spray formulations of the présent invention may include lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder as a carrier component, and especially, the spray formulation may additionally include, but is not limited to, propellants such as chlorofluorohydrocarbon, propane/butane or dimethyl ether.

The solution or émulsion formulations of the présent invention may include, but are not limited to, solvents, solubilizing agents or emulsifying agents as a carrier component, such as water, éthanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

The suspension formulation of the présent invention may include, but is not limited to, diluting agents in liquid phase, such as water, éthanol and propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum métal hydroxide, bentonite, agar and tragacanth, as a carrier component.

If the formulation of the présent invention is the surfactant-containing cleansing, the formulation may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, suifosuccinic acid monoester, isethionate, imidazolium dérivâtes, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohols, fatty acid glyceride, fatty acid diethanolamide, plant oils, lanolin dérivâtes or ethoxylated glycerol fatty acid ester as a carrier component, but is not limited thereto.

If the formulation of the présent invention is a hair shampoo, base components for forming the hair shampoo, such as thickeners, surfactants, viscosity adjusting agents, moisturizers, pH adjusting agents, antiseptics, essential oils, etc. are mixed with the compound of the présent invention. CDE can be used as a thickener, the surfactant may be LES which is an anionic surfactant and cocobetaine which is an amphoteric surfactant, the viscosity adjusting agent may be Polÿquater, the moisturizer may be glycerin, the pH adjusting agent may be citric acid or sodium hydroxide, and the preservative may be a grapefruit extract. In addition, essential oils such as cedarwood, peppermint, and rosemary, and silk amino acid, pentanol, and vitamin E can be added. According to one embodiment of the présent invention, the hair shampoo may comprise, but is not limited to, 5 to 10 parts by weight of CDE, 30 to 40 parts by weight of LES, 10 to 20 parts by weight of cocobetaine, 0.1 to 0 .-2 parts by weight of Polÿquater, 5 to 10 parts by weight of glycerin, 0.1 to 1.01 part by weight of grapefruit extract, 0.5 to 1 part by weight of silk amino acid, 0.5 to 1 part by weight of pentanol, 0.5 to 2 parts by weight of vitamin E, and 0.01 to 0.1 part by weight of any one of cedarwood, peppermint and rosemary as an essential oil, on the basis of 100 parts by weight of the compound of the présent invention.

The components included in the cosmetic composition of the présent invention may include, in addition to the compound of the présent invention as an effective component and carrier components, components commonly used in cosmetic compositions and may include, but are not limited to, conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and perfumes.

In addition, the présent invention provides a method for hair loss prévention or hair growth promotion comprising the step of transdermally administering the compound to the affected part of a subject suffering from hair loss.

The percutaneous administration may be, but not limited to, topical spreading or injection.

The affected part may include, but is not limited to, at least one selected from the group consisting of scalp, face, beard, head, mustache, body, eyebrows and eyelid part.

The subject suffering from hair loss may be a patient suffering from any one hair loss disorder selected from the group consisting of androgen alopecia, areata alopecia, systemic alopecia, degenerative alopecia, trichotillomania, telogen alopecia, anagen effluvium, alopecia cicatrisata, cicatricial alopecia, thin scalp, hair shaft dystrophy, infectious hair diseases, genetic diseases and chemotherapy, hormone imbalance, mycotic infection, and alopecia by drug ingestion.

Hereinafter, the présent invention will be described in detail with reference to Examples and Experimental Examples.

However, the following Examples and Experimental Examples are provided only for illustrating the présent invention, and the content of the présent invention is not limited by the following Examples and Experimental Examples.

<Example 1> Synthesis and solubility évaluation of compound of the présent invention <1-1> Synthesis of peptide <1-1-1> Synthesis of peptide of SEQ ID NO: 3

700 mg of chlorotrityl chloride resin (CTL resin, Nova biochem [0064] Cat No. 01-64-0021) was placed in a reaction vessel, and 10 ml of methylene chloride (MC) was added thereto, followed by stirring for 3 minutes. The solution was removed, and 10 ml of dimethyl formamide (DMF) was added thereto. After stirring for 3 minutes, the solvent was removed again. 10 ml of dichloromethane solution was added to the reactor, and after adding 200 mmol of Fmoc-Cys (trt)OH (Bachem, Swiss) and 400 mmol of diisopropylethylamine (DIEA) were added, stirred and thus dissolved well, and reacted with stirring for 1 hour. After the reaction, washing was performed, and methanol and DIEA (2:1) were dissolved in dichloromethane (DCM), reacted for 10 minutes, and washed with excess DCM/DMF (1:1) . The solution was removed, and 10 ml of dimethyl formamide (DMF) was added thereto. After stirring for 3 minutes, the solvent was removed again. 10 ml of the deprotection solution (20% piperidine/DMF) was added to the reaction vessel, stirred for 10 minutes at room température, and then the solution was removed. The same amount of the deprotection solution was added, and the reaction was maintained for 10 minutes. Then, the solution was removed, and washed twice with DMF, once with MC and once with DMF for 3 minutes each to obtain the Cys(trt)-CTL resin.

To the new reactor, 10 ml of DMF solution was added, 200 mmol of Fmoc-His (trt)-OH (Bachem, Swiss), 200 mmol of HoBt and 200 mmol of Bop were added, stirred and dissolved well. 400 mmol of DIEA was added to the reactor in two portions and then stirred for at least 5 minutes until ali solids dissolved. The dissolved amino acid mixture solution was placed in the reaction vessel containing the deprotected resin and allowed to react for 1 hour at room température with stirring. The reaction solution was removed, and stirred with DMF solution three times for 5 minutes each, and then removed. A small amount of the reaction resin was taken and the degree of reaction was checked using a Kaiser test (Nihydrin Test). His(trt)-Cys(trt)-CTL resin was prepared by deprotecting twice in the same manner as described above while using the deprotection solution. After thoroughly washing with DMF and MC and performing a Kaiser test once again, the following amino acid adhesion experiment was performed as described above.

Based on the selected amino acid sequence, chain reactions were performed in the order of Fmoc-Cys(trt), Fmoc-Arg, Fmoc-Gln(trt) , Fmoc-Val, Fmoc-Arg, Fmoc-Thr, FmocGln(trt) and Fmoc-Arg(pbf) . The Fmoc-protecting group was removed by reacting with the deprotection solution twice for 10 min and then washing well. Acetic anhydride, DIEA and

HoBt were added and acétylation was carried out for 1 hour, and then the peptidyl resin thus prepared was washed three times each with DMF, MC and methanol. The nitrogen was slowly flowed and dried, and then thoroughly dried by reducing the pressure under vacuum under P2O5. Thereafter, after adding 30 ml of leaving solution [95% of trifluoroacetic acid, 2.5% of distilled water, 2.5% of thioanisole], the reaction was maintained for 2 hours with occasional shaking at room température. The resin was filtered and the resin was washed with a small amount of TFA solution and then combined with the mother liquor. Distillation was carried out using reduced pressure so that the total volume remained about half, and 50 ml of cold ether was added to induce précipitation. The précipitâtes were collected by centrifugation and washed with cold ether two times. The mother liquor was removed and sufficiently dried under nitrogen to obtain 0.65g of crude NH2~Arg-GlnThr-Arg-Val-Gln-Arg-Cys-His-Cys-OH peptide (SEQ ID NO: 3) (Yield: 92.6%). A molecular weight of 1287.1 (theoretical value: 1286.5) was obtained when measured by using a molecular weight analyzer.

< 1 -1 -2> Synthesis of peptides of SEQ ID NO: 1 and SEQ ID NO : 2

The peptide (Glu-Leu-Ile-Glu-His-Gly-Gly-Gly-Arg-ProAla-Asp: ELIEHGGGRPAD) of SEQ ID NO: 1 and the peptide (AcTyr-Lys-Ser-Lys-Lys-Gly-Gly-Trp-Thr-His: Ac-YKSKKGGWTH) of

SEQ ID NO: 2 were synthesized using the same method as the

Table 1:

SEQ ID NO	Amino acid sequence	Analytical value (mass spectrometer)
Analytical value	Theoretical value
1	ELIEHGGGRPAD	1250.9	1250.35
2	Ac-YKSKKGGWTH	1233.8	1233.4
3	RQTRVERCHC	1287.1	1286.5

<l-2> Synthesis of compound of the présent invention

The peptidyl resin (1 mmol) and 3.9 g (3 mmol, 3.0 equiv.) of N,N'-diisopropylethylamine (DIPEA) in a peptide reactor were dissolved in 10 mL of 1-methyl- 2-pyrrolidinone (NMP), and then, 200 mg (2 mmol, 2.0 equiv.) of succinic anhydride was added and reacted at room température for 2 hours. The solvent was filtered off and washed with fresh NMP (5 mL X 2) to obtain a peptidyl resin-succinic acid conjugate. 270 mg (0.2 mmol, 2.0 equiv.) of 1hydroxybenzotriazole (HOBt) and 759 mg (0.2 mmol, 2.0 equiv.) of N,N,N',N'-tetramethyl-O-(IH-benzotriazol-l-yl) uronium hexafluorophosphate (HBTU) were dissolved in 10 mL of dimethyl sulfoxide (DMSO) and reacted for 30 minutes. 388 mg (0.3 mmol, 3 equiv.) of N,N-diisopropylethylamine (DIPEA), 41.8 mg (0.2 mM) of Minoxidil analogue and peptidyl resin-succinic acid conjugate (0.1 mmol) were added and reacted at room température for 72 hours, and filtered to obtain the reacted peptidyl resin. The obtained resin was reacted with cleavage solution at room température for 2 hours to remove the resin and protecting group, and crystallized using 10 mL (10 mmol) of diethyl ether to obtain a Minoxidil hybrid peptide.

[Reaction Scheme 1] Reaction scheme of conjugate of

Minoxidil and peptide

Pept ide-NH₂

NMP r t, 2h

DIPEA(3.0 equ î v. )

1)H0Bt(2.0 equiv.)

2)Cleavage solution A HBIU(2.0 equiv.) rt, 2h DIEA(3.0 equiv.)

DMSO, rt, 72h t

Pept i de-N

[Reaction Scheme 2] Reaction scheme of Minoxidil-Nokkin conjugate

0^0

NokkirrNH₂ + J

NMP rt, 2h

DIPEA(3.0 equiv.) f

H 0 Nokk i n-hH;

1)H0Bt(2.0 equiv.)

2)C!eavage solution A HBIU(2.0 equiv.) rt, 2h DIEAÎ3.0 equiv.)

DMSO, rt, 72h

Nokk i n-N

[Reaction Scheme 3] Reaction scheme o£ MinoxidilKeramin2 conjugate .(R.z>0

Keramin2-NH₂ + 0=( J

NMP rt, 2h

DIPEAÎ3.0 equiv.)

H .0

Kerami n2-N.....(

0'

2)C!eavage solution A rt, 2h

1)HOBt(2.0 equiv.)

HBIU(2.0 equiv.)

DIEA(3.0 eauiv.)

DMSO, rt, 72h

Keramin2~N

[Reaction Scheme 4] Reaction scheme of Minoxidil-WINT conjugate

<l-3> Evaluation of Solubility

The Minoxidil-CG-Nokkin, the Minoxidil-CG-Keramin2, and the Minoxidil-CG-WINT prepared in Example 1-1 were dissolved in DW at a concentration of 10 mg/ml, respectively. The Minoxidil was used as a control.

As a resuit, it was confirmed that the Minoxidil was almost insoluble in water at the same concentration and thus was in opaque state, whereas ali of the three compounds of the présent invention were (see FIG. 1) .

completely dissolved in water <Example 2> Evaluation of the degree of cell prolifération upon treatment of the compound of the présent invention <2 -1> Evaluation of cell prolifération for human umbilical vein endothélial cell (HUVEC)

In order to confirm the function of the compound of the présent invention synthesized in Example 1, HUVEC was treated with the compound of the présent invention to confirm the degree of prolifération. 3000 HUVECs were placed in each well of a 96-well plate and incubated in a CO2 incubator for 24 hours. After 24 hours, the medium was replaced with serum-free DMEM medium, and the three compounds of the présent invention synthesized in Example 1 and Minoxidil were added at 0.5 uM, 5 uM, and 50 uM concentrations, respectively, to the cells, and incubated for 72 hours. After the incubation was completed, the incubation supernatant was removed, and the cells were fixed using éthanol and washed three times with PBS (phosphate buffer saline). After removing the washing solution, the cells were treated with a colorimétrie SRB solution and washed thoroughly with 1% acetic acid. Thereafter, the cells were observed with a microscope to observe the viability of the cells. To the stained cells, 10 mM Trizma base (pH 10.5) solution were added to elute the SRB, and then the absorbance was measured by ultraviolet light of a wavelength of 560 nm to measure the viability of the cells.

As a resuit,	it was	confirmed that	in the case	of	the
three compounds	of the	présent invention at	a	low
concentration, the	cell	prolifération	was shown	to	be
similar to that of	the control group, the	Minoxidil,	but	the

degree of cell prolifération was markedly increased compared to the Minoxidil as the concentration was increased (see FIG. 2) .

<2-2> Evaluation of cell prolifération for human hair dermal papilla cells (HHDPC)

3000 HHDPCs were placed in each well of a 96-well plate and incubated in a CO2 incubator for 24 hours. The medium was replaced with serum-free DMEM medium, and the three compounds of the présent invention and Minoxidil were added at 0.5 uM, 5 uM, and 50 uM concentrations, respectively, and incubated for 72 hours. After completion of the incubation, cells were stained in the same manner as in Example 2-1, and SRB was eluted to quantify the degree of cell prolifération.

As a resuit, it was confirmed that the three compounds of the présent invention hâve a higher degree of cell prolifération than the Minoxidil, and the degree of cell prolifération is significantly increased in proportion to the treatment concentration (see FIG. 3).

<Example 3> Evaluation of the effect of the compound of the présent invention on the expression of VEGF and ΤΘΕβΙ

Since VEGF plays a rôle in angiogenesis and expansion function and TGFpi affects hair loss, the level of expression of VEGF and TGFpi was confirmed when treated with the compound of the présent invention.

<3-1> Evaluation of mRNA amount (transcription level)

VEGF was expressed by HUVECs and TGFpl was expressed by hair follicle dermal papilla cells. Two cells were placed in each 6-well plate at a rate of 1 χ 10⁵ cells/well. After 24 hours of incubation in a CO2 incubator, the medium was replaced with serum-free DMEM medium. Three compounds of the présent invention and Minoxidil were added to the cells at 5 uM and 50 uM concentration, respectively, and incubated for 24 hours. After incubated cells were harvested, RNA was extracted using an RNA extraction kit and RT-PCR was performed to confirm the degree of expression of VEGF and TGFpi. The primers used in the RT-PCR are shown in table 2. Table 2 :

Kind	of primer	Sequence	SEQ ID NO
VEGF	Forward	(5' )	CCATGAACTTTCTGCTGTCTT	(3' )	4
VEGF	Reverse	(5' )	TCGATCGTTCTGTATCAGTCT	(3' )	5
TGFpi	Forward	(5' )	GCCCTGGATACCAACTATTGC	(3' )	6
TGFpi	Reverse	(5' )	TCAGCACTTGCAGGAGTAGCG	(3' )	7
GAPDH	Forward	(5’ )	GGAGCCAAAAGGGTCATCAT	3’ )	8
GAPDH	Reverse	(5' )	GTGATGGCATGGACTGTGGT	3' )	9

As a resuit, the three compounds of the présent invention showed a higher expression of VEGF than that of the Minoxidil, and especially VEGF expressions in the case of the Minoxidil-Nokkin and the Minoxidil-Keramin2 were significantly higher than that of Minoxidil (see FIGs. 4 to 6). In addition, the expressions of TGFpl in the case of the three compounds of the présent invention were lower than that of the Minoxidil, and in particular, the expression

level of TGFpl in	the	case	of	the	Minoxidil-Nokkin	was
significantly lower	than	that	of	the	Minoxidil at the	same
concentration (see	FIGs .	4 to	6) .	From	these results, it	can

be seen that since the three compounds of the présent invention hâve a high expression amount of VEGF that plays a rôle in angiogenesis and expansion function and hâve a low expression amount of TGFpl that is involved in hair loss, the three compounds of the présent invention can be used for hair loss prévention or improvement.

<3-2> Evaluation of the amount of protein (translation level)

HUVECs were placed in each well of a 6-well plate at 1 x 10⁵ cells/well. Incubation was performed in a CO2 incubator for 24 hours. After replacing the medium with serum-free DMEM medium, the three compounds of the présent invention and the Minoxidil were added respectively to the cells at a concentration of 5 uM and 50 uM, and then incubated for 24 hours. Protein was extracted using protein extraction kit and Western blotting was performed. After preparing 12% SDSPAGE, 15 ug of protein was loaded onto the prepared SDS-PAGE and transferred to PVDF membrane. Blocking was performed with 5% skim milk solution at room température for 1 hour. The primary antibody (anti-VEGF antibody, anti-alpha tubulin antibody) was attached at a concentration of 1/3000 at room température for 2 hours. Three washes were performed with PBST for 10 minutes, and the secondary antibody was attached at a concentration of 1/5000 at room température for 1 hour. After washing three times for 15 minutes with BST, the détection was performed.

As a resuit, it was found that the three compounds of the présent invention are similar to the Minoxidil or hâve a higher than the Minoxidil with regard to the expression level of VEGF (see FIG. 7). Since the three compounds of the présent invention increase the expression of VEGF that plays a rôle in angiogenesis and expansion function, the compounds of the présent invention can be useful for hair loss prévention or improvement.

<Example 4> Evaluation of the degree of angiogenesis of the compound of the présent invention

200 μΐ of Matrigel was placed in each well of a 24-well plate and incubated for 1 hour. 1 x 10⁵ HUVECs were placed in each Matrigel. Three compounds of the présent invention and Minoxidil were added to the cell-seeded Matrigel at a concentration of 5 uM and 50 uM, respectively. VEGF used as a positive control was treated at a concentration of 50 nM and 100 nM. After 6 hours, the degree of angiogenesis of

HUVEC was observed through a microscope.

As a resuit, when treating the three compounds of the présent invention, the degree of angiogenesis was excellent, and especially was superior to the Minoxidil, and blood vessels were formed to a degree similar to that of VEGF treatment (see FIG. 8) . When the degree of angiogenesis in each experimental group was compared with regard to the number of completely formed blood vessels within a certain unit area, the three compounds of the présent invention showed relatively good angiogenesis as compared with the Minoxidil (see FIG. 9).

<Exaxnple 5> Confirmation on whether the Minoxidil-WINT of the présent invention participâtes in the translocation of β-catenin, which is a signal pathway of WINT, to nucléus

Hair follicle dermal papilla cells were placed in each well of a 6-well plate at 1 χ 10⁵ cells/well. Incubation was performed in a CO2 incubator for 24 hours. After replacing the medium with serum-free DMEM medium, the Minoxidil, the Minoxidil-WINT, and the WINT were added respectively to the cells at a concentration of 5 uM and 50 uM, and then incubated for 24 hours. Protein was extracted using a protein extraction kit (extraction of each of the nuclear/cytoplasmic protein). Western blotting was carried out in the same manner as in Example 3-2 except that an anti-beta-catenin antibody, an anti-HDAC antibody, an antialpha tubulin antibody as primary antibodies were used.

As a resuit, it was confirmed that the Minoxidil-WINT, a compound of the présent invention, at the same concentration shows a translocation of β-catenin to the nucléus, whereas the Minoxidil alone has a significantly lower degree of translocation of β-catenin to the nucléus (see FIG.10). The translocation of the Minoxidil-WINT to the nucléus was found to be at least 2.8-fold higher than the Minoxidil alone (see FIG. 11). From these results, it can be seen that since the Minoxidil-WINT, a compound of the présent invention, can transfer β-catenin, which is a signal pathway of WINT, into the nucléus and has a higher degree of translocation of β-catenin to the nucléus than the Minoxidil, the compound of the présent invention can be used for hair growth promotion or hair loss prévention.

<Example 6> Confirmation on whether the MinoxidilNokkin of the présent invention participâtes in the translocation of phospho-Smadl/5/8, which is a signal pathway of Nokkin, to nucléus

It was confirmed, on whether the Minoxidil-Nokkin of the présent invention inhibits the BMP signal pathway which is a major factor in hair loss, by the inhibition of phospho-Smadl/5/8 activation (migration from the cytoplasm to the nucléus) . The experiment was carried out in the same manner as in Example 5, except that in the presence of BMP2, the Minoxidil-Nokkin is used instead of the Minoxidil-WINT, and an anti-P-Smadl/5/8 antibody and an anti-HDACl antibody were used as primary antibodies.

As a resuit, it was confirmed that in the case of the

treatment	with	the	Minoxidil-Nokkin,	the	delivery	of	P-
Smadl/5/8	into	the	nucléus was reduced as	compared	to	the
treatment	with	the	Minoxidil, and as	the	concentration	of

the Minoxidil-Nokkin is increased, P-Smadl/5/8 in the nucléus was further decreased (see FIGs. 12 and 13) . From

these results, it can	be	seen that	since	the	Minoxidil-
Nokkin of	the présent	invention can	block	the	BMP	signal
pathway to	hair loss,	the	Minoxidil-	•Nokkin	of	the	présent

invention can be used for hair growth promotion or hair loss prévention.

with the compound of the <Example 7> Identification of hair growth when treating présent invention

The Minoxidil-Nokkin of the présent invention was applied to 6 male C57BL mice at 7 weeks of âge to détermine the degree of hair growth. The hair on the back of 7 weeks old C57BL/6 mice was depilated using a hair removal cream. The Minoxid.il and the Minoxidil-Nokkin were added to PBS at concentrations of 100 ug/ml, respectively, to préparé a sample. The sample was applied to the dorsal skin of the mouse evenly once a day. After observing on whether the hair on the dorsal skin of the mouse was grown, photographs were taken from the point where the color of the dorsal skin was changed to black. For the histological examination, mice were slaughtered, the dorsal skins of mice were collected, fixed in 4% PFA, and embedded in paraffin. The embedding block was sectioned at 4 pm, stained with H&E and the hair follicle was observed.

As a resuit, it was confirmed that when the compound of the présent invention was applied, the hair growth rate was 10 remarkably faster than that of the control group not treated with the sample or the group treated with the Minoxidil (see

FIG. 14) . When the hair follicle was examined by the H&E test, it was confirmed that in the case of the group treated with the compound of the présent invention, the hair 15 follicle was deeply located in the skin and the number of hair follicles was larger as compared with the control or the Minoxidil treated group, and the growth and development of hair follicles are promoted in a form in which the hair root in the hair follicle grows long and grows onto the 20 surface of the skin (see FIG. 15) . From the above results, it can be seen that the compound of the présent invention can be used for hair growth promotion or hair loss prévention.

formulation Example>

Formulation Example 1 : Emollient beauty wash

Άη emollient beauty wash comprising the compound of the présent invention prepared in the above Example 1-2 and having the following composition was prepared according to a préparation method of a general beauty wash.

Table 3:

Component	Content(wt.%)
Compound of the présent invention	2.5
1,3-Butylene glycol	6
Glycérine	4
PEG 1500	1
Sodium hyaluronate	1
Polysorbate 20	0.5
Ethanol	8
Antiseptics, Coloring agents	q. s .
Benzophenone-9	0.05
Perfumes	Trace
Purified water	Remainder
Total	100

ΙΟ

Formulation Example 2. Nutrition cream

A	nutrition	cream comprising	the	compound of	the
présent	invention	prepared in the	above	Example 1-2	and
having	the following composition was	prepared according	to a

préparation method of a general nutrition cream.

Table 4 :

Component	Content(wt.%)
Compound of the présent invention	2.5
Meadowfoam oil	3
Cetearyl alcohol	1.5
Stearic acid	1.5
Glyceryl stéarate	1.5
Liquid paraffin	10
Beeswax	2
Polysorbate 60	0.6

Sorbitan sesquioleate	2.5
Squalane	3
1,3-Butylene glycol	3
Glycérine	5
Triéthanolamine	0.5
Tocopheryl acetate	0.5
Antiseptics, Coloring agents	q. s .
Perfurnes	q.s.
Purified water	Remainder
Total	100

Formulation Example 3. Nutrition beauty wash

A nutrition beauty wash comprising the compound of the présent invention prepared in the above Example 1-2 and having the following composition was prepared according to a préparation method of a general beauty wash.

Table 5 :

Component	Content(wt.%)
Compound of the présent invention	2.5
1,3-Butylene glycol	4
Glycérine	4
Cetearyl alcohol	0.8
Glyceryl stéarate	1
Triethanolamine	0.13
Tocopheryl acetate	0.3
Liquid paraffin	5
Squalane	3
Macadamia nut oil	2
Polysorbate 60	1.5
Sorbitan sesquioleate	0.5
Carboxyvinyl polymer	1
Antiseptics, Coloring agents	q.s.
Perfumes	q.s.
Purified water	Remainder
Total	100

Formulation Example 4. Essence

An essence comprising the compound of the présent invention prepared in the above Example 1-2 and having the following composition was prepared according to a préparation method of a general essence.

Table 6 :

Component	Content(wt.%)
Compound of the présent invention	2.5
Glycérine	10
1,3-Butylene glycol	5
PEG 1500	2
Allantoin	0.1
DL-Panthenol	0.3
EDTA-2Na	0.02
Hydroxyethyl cellulose	0.1
Sodium hyaluronate	8
Carboxyvinyl polymer	0.2
Triethanolamine	0.18
Octyldodeceth-16	0.4
Ethanol	6
Perfumes, Antiseptics, Coloring agents	g.s.
Purified water	Remainder
Total	100

Formulation Example 5. Haïr sérum

A hair sérum comprising the compound of the présent invention prepared in the above Example 1-2 and having the 10 following composition was prepared according to a préparation method of a general hair sérum.

Table 7 :

Component	Content (wt.%)
Compound of the présent invention	1
Glycérine	10
1,3-Butylene glycol	5

PEG 1500	2
Allantoin	0.1
DL-Panthenol	0.3
EDTA-2Na	0.02
Hydroxyethyl cellulose	0.1
Sodium hyaluronate	8
Carboxyvinyl polymer	0.2
Triéthanolamine	0.18
Octyldodeceth-16	0.4
Ethanol	6
Perfurnes, Antiseptics, Coloring agents	q. s .
Purified water	Remainder
Total	100

Formulation Example 6. Hair toner

A hair toner comprising the compound of the présent invention prepared in the above Example 1-2 and having the following composition was prepared according to a préparation method of a general hair toner.

Table 8:

Component	Content(wt.%)
Compound of the présent invention	1
Glycérine	2
1,3-Butylene glycol	2
PEG 1500	2
Allantoin	0.1
DL-Panthenol	0.3
EDTA-2Na	0.02
Sodium hyaluronate	8
Carboxyvinyl polymer	0.2
Triéthanolamine	0.18
Ethanol	10
Perfurnes, Antiseptics, Coloring agents	q. s .
Purified water	Remainder
Total	100

While the preferred embodiments of the présent invention hâve been illustrated by way of example, the scope of the présent invention is not limited to the spécifie embodiments described above. Those skilled in the art will 5 appreciate that various modifications may be made without departing from the scope of the claims of the présent invention.

Claims (1)

1. A compound having a structure in which Minoxidil and

peptide 2 . are chemically bonded. The compound according to claim 1, wherein the peptide consists of 2 · to 30 amino acid sequences. 3 . The compound according to claim 2, wherein the peptide consists of 8 ’ to 15 amino acid sequences. 4 . The compound according to claim 1, wherein the peptide is a ¹ rater-soluble peptide. 5 . The compound according to claim 4, wherein the water-soluble peptide : has a ratio of hydrophilic side chain- containing amino acids of no less than 50%. 6. The compound according to claim 5, wherein the water-soluble peptide has a ratio of hydrophilic side chain- containing amino acids of no less than 70%. 7 . The compound according to claim 6, wherein the water-soluble peptide has a ratio of hydrophilic side chain- containing amino acids of no less than 90% . 8 . The compound according to claim 5, wherein the

hydrophilic side chai-containing amino acid is selected from the group consisting of arginine (Arg), histidine (His), lysine (Lys), asparaginic acid (Asp), glutamic acid (Glu), serine (Ser), threonine (Thr), asparagine (Asn), glutamine (Gin), cysteine (Cys), selenocysteine (Sec), glycine (Gly) and proline (Pro).

9. The compound according to claim 4, wherein the water-soluble peptide has 5 or less hydrophobie side chaincontaining amino acids.

10. The compound according to claim 9, wherein the water-soluble peptide has 3 or less hydrophobie side chaincontaining amino acids.

11. The compound according to claim 9, wherein the hydrophobie side chain-containing amino acid is selected from the group consisting of alanine (Ala), valine (Val), isoleucine (Ile), leucine (Leu), méthionine (Met), phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp).

12. The compound according to claim 1, wherein the peptide is selected from the group consisting of Nokkin peptide consisting of the amino acid sequence of SEQ ID NO: 1; Keramin2 peptide consisting of the amino acid sequence of SEQ ID NO: 2; and WINT peptide consisting of the amino acid sequence of SEQ ID NO: 3.

13. A pharmaceutical composition for hair loss prévention or hair growth promotion comprising the compound of any one of daims 1 to 12.

14. A cosmetic composition for hair loss prévention or hair growth promotion comprising the compound of any one of daims 1 to 12.

15. The cosmetic composition according to claim 14, wherein the cosmetic composition is a formulation selected from the group consisting of emollient beauty wash, nutrition beauty wash, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, powder, hair tonie, hair cream, hair lotion, hair shampoo, hair rinse, hair

5 conditioner, hair-spray, hair air-sol, pomade, sol-gel, émulsion, oil, wax and air-sol.

16. A method for preventing hair loss or promoting hair growth comprising the step of transdermally administering the compound of any one of claims 1 to 12 to the affected 10 part of the individual suffering from hair loss.