Peptide having activities of hair growth promotion and damaged hair improvement and uses thereof

Abstract

A peptide with the activity of promoting hair growth and improving damaged hair is provided, as well as its use. A peptide composed of an amino acid sequence represented by Arg-Cys-Cys-Gly or Glu-Glu is provided; a cosmetic composition comprising the peptide for improving the condition of damaged hair; a cosmetic composition comprising the peptide for alleviating hair loss or promoting hair growth; and a pharmaceutical composition comprising the peptide for preventing or treating hair loss.

Description

Peptide having the activity of promoting hair growth and improving damaged hair and its use CROSS-REFERENCE TO RELATED APPLICATIONS This application is based upon and claims the benefit of priority under 35 U.S.C. §119 to Korean Patent Application No. 10-2022-0155815, filed on November 18, 2022, in the Korean Intellectual Property Office, and Korean Patent Application No. 10-2023-0149274, filed on November 1, 2023, in the Korean Intellectual Property Office, the disclosures of which are incorporated herein by reference in their entirety. FIELD OF THE INVENTION The present disclosure relates to a peptide having the activity of promoting hair growth and improving damaged hair and its use. Background of the Invention The human scalp contains approximately 150,000 hairs, each undergoing a distinct hair cycle, a repetitive process of growth and shedding. The hair growth cycle is broadly divided into three phases: anagen, the growth phase during which hair grows; catagen, the shedding phase during which hair growth ceases and remains; and telogen, the resting phase during which dermal papilla cells shrink and hair follicles contract, leading to hair loss. These three phases repeat cyclically. The hair growth cycle varies depending on internal factors such as family history, genetic factors, physical constitution, and hormonal regulation, as well as external factors such as nutritional status, aging, environmental factors, and stress. Furthermore, because the ends of the hair are exposed to the external environment for longer periods than the hair closer to the scalp, the external environment causes more severe damage to the ends. Weathering caused by exposure to the external environment leads to loss of the hair cuticle, split ends, and ultimately breakage. Continuous heating of hair using a hair dryer or similar is a typical example of an environment that causes hair damage, such as decreased hair tension and weakening. Furthermore, various physical, chemical, or environmental factors, such as frequent perms and hair dyes, can cause proteins and lipids to leach from the hair, leading to hair thinning. Consequently, the hair becomes rough and loses its luster, and increased friction makes hair care more difficult, leading to hair breakage and split ends. Furthermore, this hair thinning reduces hair elasticity and causes hair to droop, resulting in reduced hair volume and thinning. As society ages, the number of people suffering from hair loss is increasing. Previously, hair loss primarily affected middle-aged men, but in recent years, interest in hair loss prevention and hair growth has also increased among young people and women. While hair loss has long been recognized as a common aging phenomenon, it has recently been discovered that it develops for a variety of reasons, including stress, Westernized dietary habits, nutritional imbalances, changes in social activities, and genetic factors. Currently, available US FDA-approved medications include minoxidil (6-amino-1,2-dihydro-1-hydroxy-2-imino-4-phenoxypyrimidine) (U.S. Patent No. 3,382,247) and finasteride (U.S. Patent No. 5,215,894). Minoxidil was developed in the early 1970s as a vasodilator for the treatment of hypertension. However, due to reports of hirsutism as a side effect, it has been used as a hair growth promoter. Thus, a phenomenon has been demonstrated in which hair thickening occurs by thickening hair follicles and increasing hair diameter. Furthermore, in the case of finasteride, which was originally developed as a treatment for benign prostatic hyperplasia, it is currently used as a treatment for hair loss. Thus, a phenomenon has been demonstrated in which it slows the progression of hair loss and exhibits a hair growth effect. However, minoxidil has been reported to have side effects such as weight gain, edema, dermatitis, and increased heart rate, and finasteride, which requires continuous use, has side effects such as male sexual dysfunction and birth defects in pregnant women. Therefore, there is still a need to develop a hair loss treatment without side effects. Against such a technical background, various studies are being conducted to improve the condition of damaged hair and prevent hair loss through mechanisms including hormone control and metabolic control (Korean Patent Application Publication No. 2002-0005332), but the results thereof have not been significant. Summary of the Invention Provided is a peptide consisting of an amino acid sequence represented by Arg (R)-Cys (C)-Cys (C)-Gly (G) or Glu (E)-Glu (E). Provided is a cosmetic composition for improving the condition of damaged hair, comprising a peptide including an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. Provided is a cosmetic composition for alleviating hair loss or promoting hair growth, comprising a peptide including an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. Provided is a pharmaceutical composition for preventing or treating hair loss, comprising a peptide including an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. Other objects and advantages of the present application will become more apparent from the following detailed description and the accompanying claims and drawings. The contents not described in this specification are omitted because they can be fully recognized and inferred by those skilled in the art in the field of the present application or similar technical fields. Additional aspects will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the embodiments presented in the disclosure. The descriptions and embodiments disclosed herein may also be applicable to other descriptions and embodiments, respectively. That is, all combinations of the various elements disclosed herein fall within the scope of this disclosure. In addition, the scope of this application should not be construed as being limited by the detailed description provided below. According to one aspect of the present disclosure, the peptide consists of an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E). As used herein, the term "peptide" refers to a linear molecule formed by amino acid residues linked by peptide bonds. Peptides can be prepared by any known chemical synthesis method, particularly solid-phase synthesis (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 (U.S. Patent No. 5,516,891). As a result of increased efforts to develop biologically effective peptides, the present inventors have discovered peptides having an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E). In this regard, biologically effective activity can exhibit at least one characteristic selected from the group consisting of: (a) promoting the proliferation or activation of hair follicle dermal papilla cells; (b) promoting the activation of outer root sheath cells; (c) promoting the activation of germinal matrix cells; and (d) inhibiting the expression of Dickkopf-related protein 1 (DKK-1). More specifically, the biologically effective activities may include (aa) enhancing the phosphorylation of ERF and AKT, factors associated with the proliferation of hair follicle dermal papilla cells; (bb) activating β-catenin, lymphoid enhancer binding factor-1 (LEF-1), c-Myc, and cyclin D1 in hair follicle dermal papilla cells; (cc) enhancing the expression of type I stratum corneum Ha3-II (Ha3-II), keratin 5, keratin 14, and keratin 19 in outer root sheath cells; and (dd) enhancing the expression of homeobox protein Hox-C13 (HOXC13), Msh homeobox 2 (MSX2), and forkhead box protein N1 (FOXN1) in germinal matrix cells. Therefore, the peptide can be used to alleviate hair loss or promote hair growth, prevent or treat hair loss, and improve the condition of damaged hair. A protecting group can be attached to the N-terminus or C-terminus of the peptide to obtain chemical stability, enhanced pharmacological properties (such as half-life, absorption, potency and efficacy), improved specificity (such as a broad range of biological activities) and reduced antigenicity. Therefore, the peptide can be used as the peptide itself or a protected derivative thereof. According to one embodiment, the N-terminus of the peptide can be attached to a protecting group selected from the group consisting of: acetyl, fluorenylmethoxycarbonyl, formyl, palmityl, myristyl, stearyl, butoxycarbonyl (Boc), allyloxycarbonyl (Alloc) and polyethylene glycol (PEG); and / or the C-terminus of the peptide can be attached to a protecting group selected from the group consisting of: amino (-NH 2) Tertiary alkyl and azido (-NHNH 2) In addition, the peptide may optionally include a targeting sequence, a tag, a labeling residue, and an amino acid sequence specifically constructed for the purpose of extending the half-life or stability of the peptide. Peptides may be artificially synthesized or non-naturally occurring or engineered, with "non-naturally occurring or engineered" referring to a state created by the application of artificial modifications, rather than the state in which they occur in nature. In this regard, artificial modifications may include artificially synthesizing amino acid sequences by mimicking various amino acid structures, or engineering to achieve chemical stability, enhanced pharmacological properties, improved specificity, or reduced antigenicity, as described above. As used herein, the term "stability" may refer not only to in vivo stability in which a peptide is protected from protease in an organism, but also to storage stability (storage stability at room temperature). According to another aspect of the present disclosure, a cosmetic composition for improving the condition of damaged hair comprises a peptide including an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. As used herein, the term "improving a condition" may refer to all effects that increase a parameter associated with improvement or treatment of symptoms, such as at least a reduction in the severity of symptoms. As used herein, the term "damaged hair" may refer to hair that has been altered or weakened by physical, chemical, or environmental factors. Damaged hair may, for example, be hair in which the gaps between the cuticle holding the hair are widened, or hair in which the cuticle has partially fallen off. Furthermore, damaged hair may refer to hair that has a rougher overall texture than normal hair, with increased roughness and friction, decreased elasticity and volume, and reduced tension and gloss. Furthermore, damaged hair may refer to hair in which intercysteine ​​bonds are broken due to external physical or chemical stimuli. As used herein, the term "improving the condition of damaged hair" may refer to restoring the condition of damaged hair to a normal hair condition. Improving the condition of damaged hair may include, for example, improving hair elasticity (tension) and glossiness, reducing hair roughness and friction, and restoring the hair cuticle. Furthermore, improving the condition of damaged hair may mean reconnecting or restoring cysteine ​​bonds that have been broken by external stimuli. Furthermore, this term may be used interchangeably with "promoting the regeneration of damaged hair" and "improving the protective function of hair." Although conventional functional peptides have potent biological activity, due to their large size, peptides cannot be effectively incorporated into target tissues or cells, or they disappear within a short period of time due to their short half-life. However, because the cosmetic composition according to one embodiment includes a peptide composed of 10 or fewer amino acids as an active ingredient, when topically applied to a certain area, the active ingredient has an extremely high ability to penetrate into the skin or hair, thereby, for example, restoring damaged hair. According to one embodiment, the peptide exhibits efficacy such as promoting the proliferation or activation of hair follicle dermal papilla cells, promoting the activation of outer root sheath cells, and promoting the activation of germinal matrix cells. Furthermore, in tests using human hair or human hair wigs, the peptide demonstrated enhanced tension and glossiness of damaged hair, reduced roughness and friction of damaged hair, and demonstrated excellent skin safety. In other words, these efficacy demonstrates its effects on promoting the condition of damaged hair, enhancing / regenerating damaged hair, and improving hair protection. The peptide can be used as an active ingredient in cosmetic compositions to improve the condition of damaged hair. According to one embodiment, the active ingredient of a cosmetic composition, such as a functional cosmetic composition, may include the peptide itself having the above-mentioned biological activity, a protected derivative thereof, or a peptide comprising the amino acid sequence of the peptide as a basic backbone and extended terminal portions (e.g., 10-mer, 9-mer, 8-mer, 7-mer, 6-mer, and 5-mer peptides). The cosmetic composition may include, but is not limited to, a cosmetically effective amount of a peptide and / or a cosmetically acceptable carrier. As used herein, the term "cosmetically effective amount" may refer to an amount sufficient to achieve the effect of the cosmetic composition in alleviating hair loss or promoting hair growth. The weight ratio of the peptide to the cosmetically acceptable carrier can be, for example, from about 500:1 to about 1:500. For example, the weight ratio can be from about 450:1 to about 1:450, from about 400:1 to about 1:400, from about 350:1 to about 1:350, from about 300:1 to about 1:300, from about 250:1 to about 1:250, from about 200:1 to about 1:200, from about 150:1 to about 1:150, from about 100:1 to about 1:100, from about 80:1 to about 1:80, from about 60:1 to about 1:60, from about 40:1 to about 1:40, from about 20:1 to about 1:20, from about 10:1 to about 1:10, from about 8:1 to about 1:8, from about 6:1 to about 1:6, from about 4:1 to about 1:4, or from about 2:1 to about 1:2, but is not limited thereto. The cosmetic composition may be prepared as any formulation commonly produced in the art, such as, but not limited to, solutions, suspensions, emulsions, pastes, gels, creams, lotions, sprays, powders, soaps, oils, foundations, liquid foundations, wax foundations, and sprays. The cosmetic composition may be prepared as a formulation selected from, but not limited to, scalp treatment agents, scalp cleansers, scalp massagers, scalp care products, cleansers, shampoos, conditioners, hair lotions, hair washes, hair gels, hair packs, hair masks, hair shiners, ointments, hair fixatives, hair dyes, and perms. When the cosmetic composition is formulated as a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, polysilicone, bentonite, talc or zinc oxide can be used as a carrier. When the cosmetic composition is formulated as a powder or spray, lactose, talc, silicon dioxide, aluminum hydroxide, calcium silicate, or polyamide powder can be used as a carrier. For example, in the case of a spray, the cosmetic composition may further include a propellant such as a chlorofluorocarbon, propane / butane, or methyl ether. When the formulation of the cosmetic composition is a solution or an emulsion, a solvent, a solubilizer, or an emulsifier may be used as a carrier, and the cosmetic composition may include, for example, water, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol, or sorbitan fatty acid esters. When the formulation of the cosmetic composition is a suspension, a liquid diluent (such as water, ethanol or propylene glycol), a suspending agent (such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitan esters and polyoxyethylene sorbitan esters), microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth gum can be used as a carrier. Peptides can be incorporated into nanosomes or nanoparticles to further improve skin penetration or stability. For example, nanosomes can be prepared using a microfluidizer using lecithin as the starting ingredient and incorporated into lecithin particles. Any known method for preparing nanosomes can be used accordingly. Nanosomes can have a particle size of approximately 30 nm to approximately 200 nm. When the nanosome particle size is less than 30 nm, skin penetration progresses very rapidly, resulting in side effects on the skin. When the nanosome particle size is greater than 200 nm, skin penetration is less likely to occur, making it difficult to achieve the desired effects of the nanosome. In addition to the peptide as an active ingredient and the carrier contained in the cosmetic composition, the cosmetic composition may further include any adjuvant commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and flavorings. As an active ingredient contained in a cosmetic composition, the peptide can be included in an amount appropriately and non-limitingly selected according to the form or product and the intended use, such that, for example, the amount is from about 0.01 wt% to about 15 wt% based on the total weight of the entire cosmetic composition. Furthermore, for example, the cosmetic composition can include the peptide in an amount of 0.2 wt%, 0.5 wt%, from about 1.0 wt% to about 3.0 wt%, and preferably, from about 2.0 wt% to about 3.0 wt%, based on the total weight. The cosmetic composition may include, for example, from about 0.1 to about 1.5 wt %, for example, from about 0.2 to about 1.0 wt %, from about 0.2 to about 0.8 wt %, or from about 0.2 to about 0.5 wt % of a peptide, from about 0.2 to about 0.5 wt % of a surfactant, from 0.01 to about 0.1 wt % of a pH adjuster and / or from about 0.2 to about 0.5 wt % of a preservative, and optionally from about 4.0 to about 6.0 wt % of an emulsifier, based on the total weight of the entire cosmetic composition. According to another aspect of the present disclosure, a cosmetic composition for alleviating hair loss or promoting hair growth comprises a peptide comprising an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. The same terms or elements as those given above in the description of the peptides are as described above. As used herein, the term "alleviating hair loss" refers collectively to the process of treating, reducing, and improving the condition of hair loss or its effects. For example, it may refer to any effect that inhibits the progression of hair loss, such as promoting the proliferation or activation of dermal papilla cells, promoting the activation of outer root sheath cells, promoting the activation of germinal matrix cells, and inhibiting the expression of hair loss-inducing factors such as DKK-1. Dermal papilla cells, outer root sheath cells, and germinal matrix cells are cells that make up the hair follicle and influence hair thickness and growth. The activation of these cells influences the hair growth cycle, and the hair loss-alleviating effect may be induced through this mechanism. As used herein, the term "promoting hair growth" may refer to any action that increases hair growth in the hair follicle, as well as any action that increases the overall volume of the hair, such as actions that promote hair follicle cell proliferation, hair follicle cell activation, or hair follicle cell growth. Specifically, the hair growth cycle can be divided into: the anagen phase, which is the growth phase of hair growth; the catagen phase, which is the regression phase in which hair growth ceases and the hair bulb shrinks; the telogen phase, which is the resting phase in which dermal papilla cells cease functioning and hair remains on the scalp; and the telogen phase, in which dermal papilla cells begin functioning or old hair is shed by the growth of new hair. During the hair growth cycle, dermal papilla cells connect to capillaries and sensory nerves to supply oxygen and nutrients to germinal matrix cells, which surround the dermal papilla cells and determine the growth rate through continuous cell division and proliferation. Furthermore, outer root sheath cells are cells located in the area in contact with the basal layer of the epidermis and serve to protect the hair until keratinization is complete. According to one embodiment, the peptide promotes the proliferation or activation of hair follicle dermal papilla cells, the activation of outer root sheath cells, the activation of germinal matrix cells, and inhibits the expression of hair loss-inducing factors such as DKK-1. Therefore, the peptide can be used as an active ingredient in cosmetic compositions for alleviating hair loss or promoting hair growth. According to another aspect of the present disclosure, a method for improving the condition of damaged hair, a method for alleviating hair loss, or a method for promoting hair growth, each comprising applying a cosmetic composition to the skin or hair of an individual, the cosmetic composition comprising a peptide comprising an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. The same terms or elements as those given above in the description of the cosmetic composition are as described above. As used herein, the terms "apply," "administer," and "apply" are used interchangeably and may refer to positioning a composition of an embodiment at least partially at a desired location or placing a composition of an embodiment into a subject via an administration route. According to another aspect of the present disclosure, a pharmaceutical composition for preventing or treating hair loss comprises a peptide comprising an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. The same terms or elements as those given above in the description of the peptides are as described above. As used herein, the term "prevention" refers to all actions intended to inhibit or delay the development of a disease by administering a composition. As used herein, the term "treatment" refers to any form of treatment of a subject suffering from a disease or at risk of developing a disease that improves the subject's condition (e.g., at least one symptom), delays disease progression, delays the onset of symptoms, or slows the progression of symptoms. Thus, "treating" and "preventing" are not intended to imply a cure or complete elimination of symptoms. "Subject" refers to an individual in need of treatment for a disease, and more specifically, refers to mammals, such as humans or non-human primates, mice, dogs, cats, horses, and cows. "Hair loss," as a disease to be prevented or treated by the pharmaceutical composition, refers to a state in which hair is absent from areas where it should normally be present, and can mean that growing hair (thick, dark hair) falls off the scalp. While the causes of hair loss are not limited, it can be caused by genetic factors, hormonal imbalances, stress, exposure to air pollution, various dietary habits (such as the consumption of processed foods), and environmental influences. For example, hair loss can include hereditary androgenic alopecia (baldness), alopecia areata, tinea capitis caused by fungal infections, telogen baldness, trichotillomania, hair growth disorders, and the like. Scarring alopecia is scarring hair loss and can refer to hair loss caused by lupus, alopecia areata, lichen planus, and burns and trauma. According to one embodiment, the peptide promotes the proliferation or activation of hair follicle dermal papilla cells, the activation of outer root sheath cells, and the activation of germinal matrix cells, and inhibits the expression of hair loss-inducing factors such as DKK-1. Therefore, the peptide can be used as an active ingredient in cosmetic compositions for the prevention or treatment of hair loss. The pharmaceutical composition may include the above-mentioned peptides having biological activity, protected derivatives thereof, or peptides comprising the amino acid sequence of the peptide as the basic backbone and extended terminal portions (e.g., 10-mer, 9-mer, 8-mer, 7-mer, 6-mer and 5-mer peptides) as active ingredients. The pharmaceutical composition may include a pharmaceutically effective amount of a peptide and / or a pharmaceutically acceptable carrier, but is not limited thereto. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to achieve the preventive or therapeutic effect of the pharmaceutical composition on hair loss. Pharmaceutically acceptable carriers are commonly used to prepare formulations and may include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup, methylcellulose, methylparaben, propylparaben, talc, magnesium stearate, or mineral oil. Pharmaceutically acceptable carriers and agents suitable for use in the present disclosure are described in detail in Remington's Pharmaceutical Sciences (19th edition, 1995). The weight ratio of the peptide to the pharmaceutically acceptable carrier can be, for example, about 500:1 to about 1:500. For example, the weight ratio can be about 450:1 to about 1:450, about 400:1 to about 1:400, about 350:1 to about 1:350, about 300:1 to about 1:300, about 250:1 to about 1:250, about 200:1 to about 1:200, about 150:1 to about 1:150, about 100:1 to about 1:100, about 80:1 to about 1:80, about 60:1 to about 1:60, about 40:1 to about 1:40, about 20:1 to about 1:20, about 10:1 to about 1:10, about 8:1 to about 1:8, about 6:1 to about 1:6, about 4:1 to about 1:4, or about 2:1 to about 1:2, but is not limited thereto. In addition to the above ingredients, the pharmaceutical composition may further include a lubricant, a moisturizer, a sweetener, a flavoring agent, an emulsifier, a suspension, or a preservative, but is not limited thereto. The pharmaceutical composition can be administered orally or parenterally, preferably parenterally. In the case of parenteral administration, intramuscular injection, intravenous injection, subcutaneous injection, intraperitoneal injection, local administration, transdermal administration and the like can be used, but are not limited thereto. The daily dose of the pharmaceutical composition may be about 0.0001 μg to about 1000 μg, about 0.001 μg to about 1000 μg, about 0.01 μg to about 1000 μg, about 0.1 μg to about 1000 μg, or about 1.0 μg to about 1000 μg, but is not limited thereto, and may be specified in various ways based on factors such as formulation method, administration method, patient's age, weight, sex and pathological condition, food, administration time, administration route, excretion rate and sensitivity. The pharmaceutical compositions can be formulated into unit dosage forms or in multi-dose containers using pharmaceutically acceptable carriers and / or excipients according to methods readily practiced by those skilled in the art to which the present disclosure pertains. The formulation may be a solution, suspension or emulsion in an oily or aqueous medium, an extract, a powder, granules, a tablet or a capsule, and may further include a dispersant and / or a stabilizer. According to another aspect of the present disclosure, a method for preventing or treating hair loss comprises administering to a subject a pharmaceutical composition comprising a therapeutically effective amount of a peptide comprising an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. The same terms or elements as those given above in the description of the pharmaceutical composition are as described above. According to another aspect of the present disclosure, a food composition for improving the condition of damaged hair, preventing hair loss, or promoting hair growth comprises a peptide comprising an amino acid sequence represented by Arg (R) -Cys (C) -Cys (C) -Gly (G) or Glu (E) -Glu (E) as an active ingredient. The same terms or elements as those given above in the description of the peptides are as described above. The amount of the peptide as an active ingredient contained in the food composition can be appropriately selected based on, but not limited to, the food type, intended use, and the like, and can be, for example, from about 0.01 wt% to about 15 wt% based on the total weight of the food. Alternatively, for example, the peptide content can be from about 0.02 g to about 10 g, preferably from about 0.3 g to about 1 g, based on 100 ml of the health drink composition. Detailed description of preferred embodiments Reference will now be made in detail to the embodiments, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to like elements throughout the text. In this regard, embodiments of the present invention may have different forms and should not be construed as being limited to the description set forth herein. Therefore, the following description of the embodiments is merely by reference to the figures to explain the aspects of the present invention. As used herein, the term "and / or" includes any and all combinations of one or more of the relevant listed items. When preceding a list of elements, a statement such as "at least one of..." modifies the entire list of elements and does not modify the individual elements of the list. Hereinafter, the present disclosure will be described in detail with reference to the following examples. However, these examples are for illustrative purposes only, and the scope of the present disclosure is not limited to these examples. Experimental Examples 1. Peptide synthesis The peptides shown in Table 1 below were synthesized using an automated peptide synthesizer (Milligen 9050, Millipore, USA), and pure peptides were isolated using C18 reverse-phase high-performance liquid chromatography (HPLC, Waters Associates, USA). An ACQUITY UPLC BEH300 C18 (2.1 mm × 100 mm, 1.7 µm, Waters Co., USA) was used as the column. Table 1 Experimental Examples 2. Identification of the promoting effect on proliferation or activation of hair follicle dermal papilla cells 2-1. Identification of the effect of promoting the proliferation of hair follicle dermal papilla cells In this experimental example, the effect of the peptide according to one embodiment on the proliferation of human hair follicle dermal papilla cells (HFDPCs) was examined by evaluating the changes in the viability of the cells. Specifically, human hair follicle dermal papilla cells were cultured at 4×10 3 Cells were seeded at a density of 100 cells / well in a 96-well plate and then incubated in mesenchymal stem cell complete medium for 24 hours. Subsequently, the medium was replaced with serum-free mesenchymal stem cell complete medium and then incubated for 24 hours. Thereafter, the peptide according to one embodiment was aliquoted into it at a concentration of 500 mM, 5 μM or 50 μM, and then incubated at 37°C for 72 hours. Then, the culture was washed with PBS, and 10 μL of 5 mg / ml MTT solution was aliquoted into each well. Incubate at CO After incubating the culture in an incubator for 4 hours, the culture medium was removed and 100 μL of dimethyl sulfoxide (DMSO) was added, followed by stirring for 10 minutes. The absorbance at a wavelength of 540 nm was then measured using a spectrophotometer. An untreated group served as a control, and a group treated with 1 μM EGF served as a positive control. Therefore, as shown in FIG. 1 and FIG. 2 , it was confirmed that peptide-1 or peptide-2 promoted the proliferation of dermal papilla cells. 2-2. Identification of activation factors associated with proliferation of hair follicle dermal papilla cells In this experimental example, the effect of the peptide according to one embodiment on the activation of factors associated with the proliferation of human hair follicle dermal papilla cells was examined. Specifically, human hair follicle dermal papilla cells were cultured at 4×10 5Cells were seeded on a 6-well plate at a density of 10 cells / well and then incubated in mesenchymal stem cell complete culture medium for 24 hours. Thereafter, the peptide according to one embodiment was aliquoted into the wells at a concentration of 500 mM, 5 μM, or 50 μM, and then incubated at 37°C for 24 hours. The culture was then washed with PBS and 100 μL of lysis buffer to prepare cell lysates. Subsequently, bicinchoninic acid (BCA) was quantified to prepare equal amounts of protein samples, followed by electrophoresis using a 10% SDS-PAGE gel. Thereafter, the proteins separated by SDS-PAGE were transferred to a PVDF membrane, and the reaction was blocked with 5% skim milk at room temperature for 30 minutes. Then, phosphorylated AKT and phosphorylated ERK (cell signaling, USA) antibodies were diluted 1:1000 in 3% BSA and reacted with the blocked PVDF membrane at 4°C for 16 hours. The reaction was then washed three times with 0.1% PBS-T (PBS containing 0.1% Tween-20) for 15 minutes each and reacted with a secondary antibody diluted 1:2000 in 5% skim milk for 1 hour. The reaction was then washed three times with 0.1% PBS-T (PBS containing 0.1% Tween-20) for 15 minutes each and treated with ECL solution (GE Healthcare, USA) to examine protein expression levels. An untreated group served as a control, and a group treated with 1 μM minoxidil served as a positive control. Therefore, as shown in FIG. 3 and FIG. 4 , it was confirmed that peptide-1 or peptide-2 induced the phosphorylation of ERF and AKT, which are factors associated with the proliferation of hair follicle dermal papilla cells. 2-3. Identification of the mechanism of promoting the proliferation of hair follicle dermal papilla cells In this experimental example, the effect of a peptide according to one embodiment on the proliferation mechanism of human hair follicle dermal papilla cells was examined. Specifically, human hair follicle dermal papilla cells were cultured in the same manner as in Experimental Example 2-2 and treated with a peptide according to one embodiment. Nuclear proteins were then isolated from the culture using a nuclear protein extraction kit (Thermo Scientific, USA). Protein expression levels were then examined using antibodies against β-catenin (cell signaling, USA) and HDAC1 (Santa Cruz, USA) in the same manner as in Experimental Example 2-2. An untreated group served as a control, and a group treated with 10 ng / mL recombinant human Wnt-3a protein (rhWnt-3a, R&D Systems (USA, MN)) served as a positive control. Additionally, changes in the expression levels of lymphoid enhancer binding factor 1 (LEF-1), c-Myc, and cyclin D1, downstream target genes of the β-catenin activation mechanism, were examined. To this end, human hair follicle dermal papilla cells were cultured in the same manner as in Experimental Example 2-2 and treated with a peptide according to one embodiment. The culture was then washed with PBS and treated with 300 μL of easy blue (intron, Korea) to extract RNA. The extracted RNA was then quantified using Nanodrop, and cDNA was synthesized using the RNA as a template using a cDNA synthesis kit (enzynomics, Korea). Polymerase chain reaction (PCR) was then performed using the primers listed in Table 2 below and a PCR premix (enzynomics, Korea), followed by electrophoresis using a 1.5% agarose gel, and gene expression was examined at the RNA level using a Bio-Rad gel imaging system. Table 2 Therefore, as shown in Figures 5 and 6, it was confirmed that peptide-1 or peptide-2 caused β-catenin to migrate from the cytoplasm to the nucleus. In addition, as shown in Figures 7 and 8, it was confirmed that peptide-1 or peptide-2 activated β-catenin, and as a result, the expression of LEF-1, c-Myc, and / or cyclin D1, which are downstream target genes, increased. Experimental Examples 3. Identification of the inhibitory effect on hair loss-related factors In this experimental example, the effect of a peptide according to one embodiment on the expression of DKK-1 (Dickkopf-1), a hair loss-inducing factor, was examined. Specifically, human hair follicle dermal papilla cells were cultured in the same manner as in Experimental Example 2-2, and dihydrotestosterone (DHT), a substance that induces DKK-1 expression, was added to the cells. A peptide according to one embodiment was then aliquoted into the cells at concentrations of 500 mM, 5 μM, or 50 μM. Subsequently, protein expression levels were examined using a DKK-1 (cell signaling, USA) antibody in the same manner as in Experimental Example 2-2. An untreated group served as a control, and a group treated with 5 μM finasteride served as a positive control. Therefore, as shown in FIG. 9 and FIG. 10 , it was confirmed that peptide-1 or peptide-2 inhibited the expression of DKK-1 as a hair loss-inducing factor. Experimental Examples 4. Identification of the promoting effect on outer root sheath cell activation In this experimental example, the effects of a peptide according to one embodiment on the expression of type I stratum corneum Ha3-II (Ha3-II), keratin 5, keratin 14, and keratin 19, which are cytokeratins associated with the activation of human hair outer root sheath cells (HHORSC), were examined. Specifically, human hair outer root sheath cells were cultured at 4×10 5 Cells were seeded at a density of 10 cells / well on a 6-well plate and then incubated in mesenchymal stem cell complete medium for 24 hours. Subsequently, the medium was replaced with serum-free mesenchymal stem cell complete medium and then incubated for 24 hours. Thereafter, the peptide according to one embodiment was aliquoted into it at a concentration of 500 mM, 5 μM or 50 μM, and then incubated at 37°C for 24 hours. Next, gene expression was examined at the RNA level using the primers in Table 3 below in the same manner as in Experimental Example 2-3. At the same time, the untreated group was used as a control, and the group treated with 50 nM EGF was used as a positive control. Table 3 Therefore, as shown in FIG. 11 and FIG. 12 , it was confirmed that peptide-1 or peptide-2 increased the expression of Ha3-II, keratin 14, and keratin 19, which are outer root sheath cell activating factors. Experimental Examples 5. Identification of the role of promoting the activation of germinal stromal cells In this experimental example, the effect of a peptide according to one embodiment on the expression of Hox-C13 (HOXC13), Msh homeobox 2 (MSX2), and forkhead box protein N1 (FOXN1), which are transcription factors associated with the activation of human head hair stromal cells (HHGMCs), was examined. Specifically, human head hair stromal cells were cultured at 4×10 5 Cells were seeded at a density of 10 cells / well in a 6-well plate and then incubated in mesenchymal stem cell complete medium for 24 hours. Subsequently, the culture medium was replaced with serum-free mesenchymal stem cell complete medium and then incubated for 24 hours. Thereafter, the peptide according to one embodiment was aliquoted into it at a concentration of 500 mM, 5 μM or 50 μM, and then incubated at 37°C for 24 hours. Next, gene expression was examined at the RNA level using the primers in Table 4 below in the same manner as in Experimental Examples 2-3. At the same time, the untreated group was used as a control, and the group treated with 50 nM EGF was used as a positive control. Table 4 Therefore, as shown in FIG. 13 and FIG. 14 , it was confirmed that peptide-1 or peptide-2 increased the expression of HOXC13, MSX2, and FOXN1, which are activating factors of germinal stromal cells. Experimental Examples 6. Preparation of a composition for improving the condition of damaged hair In this experimental example, a composition for improving the condition of damaged hair was prepared, comprising a peptide according to one embodiment (Peptide-1) as an active ingredient. Specifically, the composition of Example 1 was formulated into a mist formulation using methods known in the art, according to the ingredients and amounts shown in Table 5 below. Separately, the composition of Example 2 was formulated into an emulsion formulation using methods known in the art, according to the ingredients and amounts shown in Table 6 below. Table 5 Table 6 Experimental Example 7. Identification of the Effect of Improving the Tension of Damaged Hair In this experimental example, the effects of a peptide according to one embodiment on the tension (elasticity) of damaged hair were examined. Specifically, 23 subjects were tested. After washing and drying their hair once daily for three days, the composition of Example 1 or Example 2 was evenly applied to the hair, and the hair was massaged, combed, and conditioned for 5 minutes. Hair was then collected from the subjects' occipital scalp and the back load value (force at hair breakage, gmf) was measured over time using an MTT175 (Micro Tensile Tester, Diastron Ltd., UK). The results for Examples 1 and 2 are shown below in Tables 7 and 8, and the results for one individual for Examples 1 and 2 are shown in Figures 15 and 16, respectively. These results indicate that hair tension increases with increasing breaking load values. Table 7 Table 8. As shown in Tables 7 and 8, the average breaking load value was confirmed to have increased by 15.81% immediately after one use and by 33.86% after three days of use when treated with the composition of Example 1. In the case of treatment with the composition of Example 2, the value was confirmed to have increased by 18.22% immediately after one use and by 38.96% after three days of use. Compared to the results before use, statistically significant differences (p < 0.001) were observed for Examples 1 and 2, both immediately after one use and after three days of use. Based on the results, it was confirmed that the peptide according to one embodiment has an effect of increasing the tension (elasticity) of damaged hair. Experimental Examples 8. Identification of the effect of improving hair gloss In this experimental example, the effect of a peptide according to one embodiment on the glossiness (angel rings) of damaged hair was examined. Specifically, 20 human hair wigs were tested. After washing and drying the human hair wigs, the composition of Example 1 or Example 2 was evenly applied to the human hair wigs. The wigs were then massaged, combed, and conditioned for 5 minutes. The gloss unit value was then measured at 60° using a gloss meter (Multi Gloss 268 PLUS, Konica Minolta, Japan). The results of Example 1 and Example 2 are shown in Tables 9 and 10, respectively, and indicate that the glossiness of the hair increases as the gloss unit value increases. In addition, after applying the compositions of Example 1 and Example 2 to one of the human hair wigs, photos thereof were obtained using a digital camera, and the results are shown in Figures 17 and 18. Table 9 Table 10 As shown in Tables 10 and 11, the average gloss unit value was found to increase by 78.61% immediately after one use when the composition of Example 1 was used. The average gloss unit value was found to increase by 82.15% immediately after one use when the composition of Example 2 was used. Statistically significant differences (p < 0.001) were observed between Examples 1 and 2 immediately after one use compared to the results before use. Based on the results, it was confirmed that the peptide according to one embodiment has an effect of increasing the glossiness (angel ring) of damaged hair. Experimental Examples 9. Identification of the effect on alleviating the roughness of damaged hair In this experimental example, the effect of a peptide according to one embodiment on the roughness (cuticle) of damaged hair was examined. Specifically, 23 individuals were tested using the composition of Example 1 or Example 2 in the same manner as in Experimental Example 7. Images of the hair on the occipital scalp of the individuals were obtained using a scanning electron microscope (S-4700, Hitachi, Japan) at 700x magnification, and then an image analysis program (Image J, National Institutes of Health, USA) was used to measure the variable Ra (µm), which indicates the surface roughness of the hair, over time. The results of Examples 1 and 2 are shown in Tables 11 and 12 below, respectively, and indicate that the cuticle was improved and hair roughness decreased with increasing Ra values. Additionally, the results of imaging the hair of one of the individuals treated according to Examples 1 and 2 using an electron microscope are shown in Figures 19 and 20, respectively. Table 11 Table 12 As shown in Tables 11 and 12, the average Ra value was found to be reduced by 20.04% immediately after a single use and by 35.64% after 3 days of use when treated with the composition of Example 1. The average Ra value was found to be reduced by 23.59% immediately after a single use and by 37.94% after 3 days of use when treated with the composition of Example 2. Compared to the results before use, statistically significant differences (p < 0.001) were observed between Examples 1 and 2, both immediately after a single use and after 3 days of use. Based on the results, it was confirmed that the peptide according to one embodiment has the effect of alleviating the roughness (cuticle) of damaged hair. Experimental Examples 10. Identification of friction-reducing effects on damaged hair In this experimental example, the effect of a peptide according to one embodiment on the friction of damaged hair was examined. Specifically, the composition of Example 1 or Example 2 was applied to human hair pieces (bleached hair) in the same manner as in Experimental Example 8, except that 20 human hair pieces (bleached hair) were used. The human hair pieces (bleached hair) were then evaluated by measuring the average force value (gmf / mm) indicating the average frictional force of the hair at the root region using an MTT175 (Micro Tensile Tester, Dia-stron Ltd., UK). The results for Example 1 and Example 2 are shown in Table 13 and Table 14, respectively. The results indicate that as the average horizontal force value decreases, hair friction decreases. Table 13 Table 14 As shown in Tables 13 and 14, the average horizontal force value immediately after one use was reduced by 26.94% in the case of treatment with the composition of Example 1. The average horizontal force value immediately after one use was reduced by 31.06% in the case of treatment with the composition of Example 2. Statistically significant differences (p < 0.001) were observed between Examples 1 and 2 in both cases immediately after one use compared to the results before use. Based on the results, it was confirmed that the peptide according to one embodiment has the effect of reducing friction of damaged hair. Experimental Examples 11. Evaluation of abnormal skin reactions The 23 subjects in Experimental Example 7 were observed for abnormal reactions caused by the composition. No allergic contact dermatitis or irritant contact dermatitis was observed. Furthermore, the subjects were asked to report erythema (redness), edema (swelling), scaling (dead skin cells), itching, stinging (pain), burning, stiffness, and numbness. No abnormal skin reactions were reported. Based on the results, it was confirmed that the composition including the peptide according to one embodiment is suitable for application to the skin. Provisioning Instances 1. Preparation of peptide nanosomes 50 mg of the peptide from Example 1 was dissolved in 500 ml of distilled water with thorough stirring. The mixture was mixed with 5 g of lecithin, 0.3 ml of sodium oleate, 50 ml of ethanol, and a small amount of oil, and then distilled water was added to adjust the total volume to 1 L. The mixture was then emulsified under high pressure using a microfluidizer to produce peptide nanosomes with a size of 100 nm. Deployment Example 2 . lotion A lotion comprising the peptide according to one embodiment and the following composition is prepared according to a method known in the art. Table 15 Mixing Example 3. Nourishing Cream A nourishing cream comprising the peptide according to one embodiment and the following composition is prepared according to a method known in the art. Table 16 The above description of the present disclosure is provided for illustrative purposes, and those skilled in the art will appreciate that various changes and modifications may be made without changing the technical concepts and basic features of the present disclosure. Therefore, it is apparent that the above embodiments of the present disclosure are illustrative in all aspects and do not limit the present disclosure. The peptide according to one embodiment can be used to improve the condition of damaged hair, alleviate hair loss, generate hair, and promote hair growth because the peptide promotes the proliferation and activation of dermal papilla cells, germinal matrix cells, and outer root sheath cells that constitute hair follicles, and inhibits the expression of DKKK-1, a hair loss-related factor. The peptide according to one embodiment can be used as an active ingredient of a composition for improving the condition of damaged hair, alleviating hair loss, or promoting hair growth. It should be understood that the embodiments described herein should be considered in a descriptive sense only and not for purposes of limitation. Descriptions of features or aspects within each embodiment should typically be considered applicable to other similar features or aspects in other embodiments. Although one or more embodiments have been described with reference to the drawings, it will be understood by those skilled in the art that various changes in form and details may be made herein without departing from the spirit and scope of the present disclosure as defined by the following claims. (none) The above and other aspects, features, and advantages of certain embodiments of the present disclosure will become more apparent from the following description taken in conjunction with the accompanying drawings, in which: FIG1 shows the results of identifying the cell proliferation level after adding peptide-1 according to one embodiment to hair follicle dermal papilla cells; FIG2 shows the results of identifying the cell proliferation level after adding peptide-2 according to one embodiment to hair follicle dermal papilla cells; FIG3 shows the results of identifying the phosphorylation of ERF and AKT after adding peptide-1 according to an embodiment to hair follicle dermal papilla cells. ERF and AKT are factors associated with the proliferation of hair follicle dermal papilla cells; FIG4 shows the results of identifying the phosphorylation of ERF and AKT after adding peptide-2 according to an embodiment to hair follicle dermal papilla cells. ERF and AKT are factors associated with the proliferation of hair follicle dermal papilla cells; FIG5 shows the results of identifying the migration of β-catenin from the cytoplasm to the nucleus after adding peptide-1 according to an embodiment to hair follicle dermal papilla cells. β-catenin is a factor associated with the proliferation of hair follicle dermal papilla cells. FIG6 shows the results of identifying the migration of β-catenin from the cytoplasm to the nucleus after adding peptide-2 according to an embodiment to hair follicle dermal papilla cells. β-catenin is a factor associated with the proliferation of hair follicle dermal papilla cells. FIG7 shows the results of identifying the expression levels of c-Myc and cyclin D1 after adding peptide-1 according to one embodiment to hair follicle dermal papilla cells. c-Myc and cyclin D1 are downstream target genes of the β-catenin activation mechanism; FIG8 shows the results of identifying the expression levels of LEF-1, c-Myc, and cyclin D1 after adding peptide-2 according to an embodiment to hair follicle dermal papilla cells. LEF-1, c-Myc, and cyclin D1 are downstream target genes of the β-catenin activation mechanism; FIG9 shows the results of identifying the expression level of DKK-1, a hair loss inducing factor, after adding peptide-1 according to an embodiment to hair follicle dermal papilla cells; FIG10 shows the results of identifying the expression level of DKK-1, a hair loss inducing factor, after adding peptide-2 according to an embodiment to hair follicle dermal papilla cells; FIG11 shows the results of identifying the expression levels of Ha3-II, keratin 14, and keratin 19 after adding peptide-1 according to an embodiment to outer root sheath cells. Ha3-II, keratin 14, and keratin 19 are activation factors of outer root sheath cells. FIG12 shows the results of identifying the expression levels of Ha3-II, keratin 5, keratin 14, and keratin 19 after adding peptide-2 according to an embodiment to outer root sheath cells. Ha3-II, keratin 5, keratin 14, and keratin 19 are activation factors of outer root sheath cells. FIG13 shows the results of identifying the expression levels of HOXC13, MSX2, and FOXN1, which are activation factors of germinal stromal cells, after adding peptide-1 according to one embodiment to germinal stromal cells; FIG14 shows the results of identifying the expression levels of MSX2 and FOXN1, which are activation factors of germinal stromal cells, after adding peptide-2 according to one embodiment to germinal stromal cells; FIG15 shows the results of measuring the tension of human hair over time after applying a composition according to an embodiment (Example 1); FIG16 shows the results of measuring the tension of human hair over time after applying a composition according to an embodiment (Example 2); FIG17 is a photograph of a human hair wig obtained using a digital camera after applying a composition according to an embodiment (Example 1) to the human hair wig; FIG18 is a photograph of a human hair wig obtained using a digital camera after applying a composition according to an embodiment (Example 2) to the human hair wig; FIG19 shows the results of observing the roughness of hair (cuticle) over time by using an electron microscope after applying a composition according to an embodiment (Example 1) to human hair; and FIG. 20 shows the results of observing the roughness of hair (cuticle) over time by using an electron microscope after applying a composition according to an embodiment (Example 2) to human hair. TW202426469A_112143675_SEQL.xml

Claims

1. The use of a peptide composed of an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) in the preparation of a cosmetic composition for improving the condition of damaged hair, wherein the damaged hair is selected from: hair with widened gaps between hairs where the cuticle is retained; hair with partially lost cuticle; and hair with a rough overall texture and reduced elasticity and volume compared to normal hair; wherein improving the condition of damaged hair is selected from: restoring the cuticle of the hair, improving the elasticity and shine of the hair, and reducing the roughness and friction of the hair.

2. As claimed in claim 1, wherein one N-terminus of the peptide is bound to a protecting group selected from: acetyl, fluorenylmethoxycarbonyl group, methacryl, palmityl, myristyl, stearyl, butoxycarbonyl, allyloxycarbonyl, and polyethylene glycol (PEG).

3. As claimed in claim 1, wherein one C-terminus of the peptide is bound to a protecting group selected from: an amino group (-NH2), a tertiary alkyl group, and a hydrazine group (-NHNH2).

4. As claimed in claim 1, wherein the peptide exhibits at least one of the following characteristics: (a) promoting the proliferation or activation of dermal papilla cells of hair follicles; (b) promoting the activation of outer root sheath cells; (c) promoting the activation of germinal matrix cells; and (d) inhibiting the expression of Dickkopf-associated protein 1 (DKK-1).

5. The use of a peptide composed of an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) in the preparation of a cosmetic composition for relieving hair loss or promoting hair growth.

6. As claimed in claim 5, wherein one N-terminus of the peptide is bound to a protecting group selected from: acetyl, fluorenylmethoxycarbonyl, methacryl, palmityl, myristyl, stearyl, butoxycarbonyl, allyloxycarbonyl, and polyethylene glycol (PEG).

7. As claimed in claim 5, wherein one C-terminus of the peptide is bound to a protecting group selected from: an amino group (-NH2), a tertiary alkyl group, and a hydrazine group (-NHNH2).

8. Use of a peptide composed of an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) in the preparation of a pharmaceutical composition for the prevention or treatment of hair loss.

9. As claimed in claim 8, wherein one N-terminus of the peptide is bound to a protecting group selected from: acetyl, fluorenylmethoxycarbonyl, methacryl, palmityl, myristyl, stearyl, butoxycarbonyl, allyloxycarbonyl, and polyethylene glycol (PEG).

10. As claimed in claim 8, wherein one C-terminus of the peptide is bound to a protecting group selected from: an amino group (-NH2), a tertiary alkyl group, and a hydrazine group (-NHNH2).

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