Peptide capable of promoting hair growth and improving damaged hair activity and application thereof

Abstract

The present application relates to a peptide having an activity of promoting hair growth and improving damaged hair and a use thereof, and provides a peptide consisting of an amino acid sequence represented by Arg-Cys-Gly or Glu-Glu, a cosmetic composition for improving damaged hair comprising the peptide, a cosmetic composition for improving hair loss or promoting hair growth comprising the peptide, and a method for improving hair loss or promoting hair growth comprising the peptide. And a pharmaceutical composition for preventing or treating alopecia comprising the peptide.

Description

Technical Field

[0001] The present application relates to a peptide having the functions of promoting hair growth and improving the activity of damaged hair and its uses. Background Art

[0002] Human hair is composed of approximately 150,000 hairs, and each hair undergoes different hair cycles, repeating the processes of hair growth and shedding. The hair growth cycle is mainly divided into three stages, which are periodically repeated: the anagen phase of hair growth, the catagen phase of ending growth and maintaining the hair, and the telogen phase of hair loss caused by the contraction of the dermal papilla and the gradual atrophy of the hair follicle. The hair growth cycle varies due to internal factors such as family history, genetics, constitution, and hormonal regulation, as well as external factors such as nutritional status, aging, the surrounding environment, and stress.

[0003] On the other hand, since the ends of the hair are exposed to the external environment for a longer time than the scalp side, the damage caused by the external environment to the hair is more serious. The weathering caused by exposure to the external environment results in the loss of the hair cuticle, causing the ends of the hair to split and eventually break. Continuously using tools such as hair dryers to apply high heat to the hair, resulting in a reduction and weakening of the hair tension, is a typical example of such damage. In addition, various physical, chemical, or environmental factors such as frequent perming and hair dyeing can cause the dissolution of proteins and lipids inside the hair, promoting the porosity of the hair. As a result, the hair becomes rough, loses luster, has an increased friction, making it difficult to comb, and is prone to breakage or splitting. In addition, this porosity of the hair causes the hair to lose elasticity, making the hair droop and lose its fullness or become thinner.

[0004] In addition, with the development of an aging society, the number of people troubled by hair loss is increasing. In the past, this was mainly a problem for middle-aged men, but recently, young people and women have also shown increasing concern about preventing hair loss and hair care. On the other hand, hair loss has always been regarded as a sign of aging, but recent research has shown that in addition to genetic factors, various factors such as stress, Westernized eating habits, nutritional imbalances, and changes in social activities can also cause hair loss. Currently, the drugs with hair growth effects that have obtained FDA approval in the United States are minoxidil (6-Amino-1,2-dihydro-1-hydroxy-2-imino-4-phenoxypyrimidine) (U.S. Patent No. 3382247) and finasteride (U.S. Patent No. 5215894). For minoxidil, it was initially developed as a vasodilator for treating hypertension in the early 1970s. However, due to the side effect of hirsutism being reported, it is now used as a drug to promote hair growth, and it has the effect of thickening hair by enlarging hair follicles and increasing hair diameter. In addition, for finasteride, it was initially developed as a therapeutic agent for prostatic hyperplasia, but now it is used as a hair loss treatment agent, which has the effect of slowing down the hair loss process and promoting hair growth. However, there have been reports of side effects such as weight gain, edema, dermatitis, and increased heart rate for minoxidil, and finasteride requires continuous administration, and there are side effects such as sexual dysfunction in men and birth defects in infants born to pregnant women. Therefore, there is still a need to develop a hair loss treatment agent without side effects.

[0005] In this technical background, although extensive research is being conducted to improve damaged hair and prevent hair loss through mechanisms such as hormone regulation and metabolic regulation (Korean Patent Publication No. 2002-0005332), it is still insufficient at present. Summary of the Invention

[0006] Technical Problem

[0007] One aspect of the present invention provides a peptide composed of an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E).

[0008] Another aspect of the present invention provides a cosmetic composition for improving damaged hair, which comprises: a peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

[0009] Another aspect of the present invention provides a cosmetic composition for improving hair loss or promoting hair growth, which comprises: a peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

[0010] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating hair loss, which comprises: a peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

[0011] Other objects and advantages of the present application will become more apparent from the following detailed description in conjunction with the appended claims and drawings. Contents not described in this specification are omitted because those skilled in the art of the present application or similar technical fields can fully recognize and infer them.

[0012] Technical solution

[0013] Each description and embodiment disclosed in the present application can also be applied to other descriptions and embodiments. That is, all combinations of the various technical features disclosed in the present application fall within the scope of the present application. In addition, it should be noted that the scope of the present application is not limited by the following specific description.

[0014] One aspect of the present invention provides a peptide composed of an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E).

[0015] As used herein, the term "peptide" may refer to a linear molecule formed by binding amino acid residues to each other through peptide bonds. The peptides can be prepared according to chemical synthesis methods known in the art, particularly solid-phase synthesis techniques (Merrifield, J. Amer. Chem. Soc. 85: 2149-54 (1963); Stewart, et al., Solid Phase Peptide Synthesis, 2nd ed., Pierce Chem. Co.: Rockford, Ill. (1984)) or liquid-phase synthesis techniques (U.S. Patent No. 5,516,891). Through diligent research, the inventors developed peptides with biologically effective activities and successfully identified peptides composed of amino acid sequences represented by Arg (R)-Cys (C)-Cys (C)-Gly (G) or Glu (E)-Glu (E). Among them, the biologically effective activities can be manifested as any one or more 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 hair matrix cells; and (d) inhibiting the expression of DKK-1 (Dickkopf-related protein 1). More specifically, the biologically effective activities may refer to (aa) enhancing the phosphorylation of factors ERK and AKT related to the proliferation of dermal papilla cells of hair follicles; (bb) activating β-catenin, Lymphoid enhancer-binding factor-1 (LEF-1), c-Myc, and cyclin D1 in dermal papilla cells of hair follicles; (cc) enhancing the expression of Ha3-II (type I cuticular Ha3-II), Keratin 5, Keratin 14, and Keratin 19 in outer root sheath cells; (dd) enhancing the expression of Homeobox protein Hox-C13 (HOXC13), Msh homeobox 2 (MSX2), and Forkhead box protein N1 (FOXN1) in hair matrix cells. Therefore, the peptides can be used to improve hair loss or promote hair growth, prevent or treat hair loss, and improve damaged hair.

[0016] To obtain chemical stability, enhanced pharmacological properties (half-life, absorbability, titer, efficacy, etc.), altered specificity (e.g., broad-spectrum biological activity), and reduced antigenicity, the peptide may have a protecting group bound to the N-terminus or C-terminus of the peptide. Thus, the peptide can be used in all forms including the peptide itself or a derivative thereof with a protecting group introduced (a protected derivative thereof). According to a specific embodiment, the N-terminus of the peptide can be bound to any one of the protecting groups selected from an acetyl group, a fluoreonylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, a butoxycarbonyl group (Boc), an allyloxycarbonyl group (Alloc), and a polyethylene glycol (PEG); and / or the C-terminus of the peptide can be bound to any one of the protecting groups selected from an amino group (-NH2), a tertiary alkyl group, and a hydrazino group (-NHNH2). Additionally, the peptide may optionally include a targeting sequence, a tag, a labeled residue, a half-life, or an amino acid sequence prepared for a specific purpose of increasing the stability of the peptide.

[0017] The peptide is artificially synthesized, or non-naturally occurring or engineered, where "non-naturally occurring or engineered" means a state that does not exist in a natural state but is produced through artificial modification. Among them, the artificial modification can include artificially synthesizing an amino acid sequence by mimicking the structures of multiple amino acids, or the modification carried out as described above to obtain chemical stability, enhanced pharmacological properties, altered specificity, or reduced antigenicity.

[0018] As used herein, the term "stability" can refer not only to the in vivo stability of protecting the peptide from the attack of proteolytic enzymes in the body but also to storage stability (e.g., storage stability at room temperature).

[0019] Another aspect of the present invention provides a cosmetic composition for improving damaged hair, which comprises: a peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

[0020] As used herein, the term "improve" can refer to all actions that relieve a condition or at least reduce a parameter related to treatment, such as the degree of symptoms.

[0021] As used herein, the term "damaged hair" can refer to hair that has been deformed or weakened due to physical, chemical, or environmental factors. The damaged hair can, for example, include hair in a state where the gaps between the cuticle layers constituting the hair are enlarged, or a part of the cuticle has peeled off. In addition, the damaged hair can refer to hair in which, compared with normal hair, the tensile strength and glossiness are reduced, while the roughness and frictional force are increased, resulting in a rough overall hair texture and a reduction in hair elasticity and fullness. Additionally, the damaged hair can also refer to hair in a state where the intermolecular disulfide bonds within the hair are broken due to physical or chemical external stimuli.

[0022] As used herein, the term "improve damaged hair" can refer to restoring the above-mentioned damaged hair state to a normal hair state. The improvement of damaged hair can, for example, refer to enhancing hair elasticity (tensile strength) and glossiness, reducing hair roughness and frictional force, and restoring the cuticle layer within the hair. Additionally, the improvement of damaged hair can also refer to reconnecting or restoring the intermolecular disulfide bonds that have been broken due to external stimuli. Furthermore, the term can be used interchangeably with terms such as "promote the regeneration of damaged hair" and "enhance the hair protection function".

[0023] The disadvantage of existing functional peptides is that, although they have effective biological activities, they cannot be effectively introduced into target tissues or cells due to the size of the peptides themselves, or have a very short half-life and disappear from the body within a short time. On the other hand, the cosmetic composition according to an embodiment comprises a peptide composed of 10 or fewer amino acids as an active ingredient. Accordingly, the skin or hair permeability of the active ingredient is very excellent. For example, when topically applied to a specific area, it can improve the state of damaged hair.

[0024] According to an embodiment, the peptide shows effects such as promoting the proliferation or activation of dermal papilla cells in hair follicles, promoting the activation of outer root sheath cells, and promoting the activation of hair matrix cells. In addition, in experiments using human hair or human hair wigs, it was confirmed that the peptide has an improving effect on the tensile strength, glossiness, roughness, and frictional force of damaged hair, and exhibits excellent skin safety. That is, the above effects prove the effects of improving / promoting the regeneration of damaged hair and enhancing the hair protection function, and the peptide can be used as an active ingredient in a cosmetic composition for improving damaged hair.

[0025] According to a specific embodiment, the active ingredient of the cosmetic composition, such as a functional cosmetic composition, may include the peptide itself having the above biological activity, a derivative with a protecting group introduced, or a peptide with an extended terminal region based on the amino acid sequence of the peptide (e.g., 10-mer, 9-mer, 8-mer, 7-mer, 6-mer, 5-mer peptide).

[0026] The cosmetic composition may include, but is not limited to, a cosmetically effective amount of the peptide; and / or a cosmetically acceptable carrier.

[0027] As used herein, the term "cosmetically effective amount" may refer to an amount sufficient to achieve the effect of improving hair loss or promoting hair growth of the cosmetic composition.

[0028] The weight ratio between the peptide and the cosmetically acceptable carrier may be, for example, from 500:1 to 1:500. As an example, the weight ratio may be from 450:1 to 1:450, from 400:1 to 1:400, from 350:1 to 1:350, from 300:1 to 1:300, from 250:1 to 1:250, from 200:1 to 1:200, from 150:1 to 1:150, from 100:1 to 1:100, from 80:1 to 1:80, from 60:1 to 1:60, from 40:1 to 1:40, from 20:1 to 1:20, from 10:1 to 1:10, from 8:1 to 1:8, from 6:1 to 1:6, from 4:1 to 1:4, or from 2:1 to 1:2, but is not limited thereto.

[0029] The cosmetic composition may also be made into any dosage form commonly prepared in the art. For example, it may be formulated into a solution, suspension, emulsion, paste, gel, cream, lotion, milk cream, toner, powder, soap, oil, powder foundation, emulsion foundation, wax foundation, and spray, etc., but is not limited thereto. The cosmetic composition may be made into any one selected from scalp care agents, scalp cleaners, scalp massagers, scalp maintenance agents, cleaning agents, shampoos, moisturizers, hair conditioners, hair creams, hair gels, hair masks, hair care masks, hair essence, ointments, hair styling agents, hair dyes, and hair perming agents, but is not limited thereto.

[0030] When the dosage form of the cosmetic composition is a paste, cream, or gel, animal oils, vegetable oils, waxes, paraffins, starches, gum arabic, cellulose derivatives, polyethylene glycols, silicones, bentonite, silica, talc, or zinc oxide, etc. may be used as carrier components.

[0031] When the dosage form of the cosmetic composition is powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder can be used as the carrier component. For example, when it is a spray, it can also include propellants such as chlorofluorocarbons, propane / butane or dimethyl ether.

[0032] When the dosage form of the cosmetic composition is solution or emulsion, solvents, solubilizers or emulsifying agents are used as the carrier components, and can include, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, fatty acid esters of glycerol, polyethylene glycol or sorbitol.

[0033] When the dosage form of the cosmetic composition is suspension, liquid diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitan esters and polyoxyethylene sorbitan anhydride esters, microcrystalline cellulose, aluminum hydroxide methyl, bentonite, agar or gum arabic can be used.

[0034] To further improve skin penetration problems or stability problems, the peptide can be included in nanobodies or nanoparticles. For example, the nanobodies can be prepared using a microfluidizer with lecithin as the raw material and can be included within lecithin particles. Any known method can be used for the preparation method of the nanobodies. The size of the nanobody particles is preferably 30 nm to 200 nm. If the size of the nanobody particles is less than 30 nm, skin penetration may occur very quickly, causing skin side effects, while if it exceeds 200 nm, skin penetration may not be easy, thus making it difficult to obtain the effects of using the nanobody structure.

[0035] In addition to the peptide as the active ingredient and the carrier component, the components included in the cosmetic composition can also include components commonly used in cosmetic compositions, such as conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances.

[0036] The content of the peptide as an active ingredient contained in the cosmetic composition can be appropriately selected according to the type of the product, the desired use, etc. without limitation. For example, it can be added in an amount of 0.01% by weight to 15% by weight of the total weight of the cosmetic composition. Additionally, for example, based on the total weight of the cosmetic composition, in % by weight, the cosmetic composition can include 0.2%, 0.5%, 1.0% to 3.0% of the peptide, and preferably can include 2.0% to 3.0% of the peptide. Based on the total weight of the entire cosmetic composition, in % by weight, the cosmetic composition can, for example, include 0.1% to 1.5%, such as 0.2% to 1.0%, 0.2% to 0.8% or 0.2% to 0.5% of the peptide, 0.2% to 0.5% of a surfactant, 0.01% to 0.1% of a pH regulator, and / or 0.2% to 0.5% of a preservative, and optionally includes 4.0% to 6.0% of an emulsifier.

[0037] Another aspect of the present invention provides a cosmetic composition for improving hair loss or promoting hair growth, which includes: a peptide having an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

[0038] Among the terms or technical features mentioned in the description of the peptide, the same terms or technical features as those already mentioned are as described above.

[0039] As used herein, the term "improving hair loss" can comprehensively represent the process or its effects of treating, alleviating, and reducing the hair loss state. For example, it can mean all actions that inhibit the progression of hair loss, such as promoting the proliferation or activation of dermal papilla cells of the hair follicle, promoting the activation of outer root sheath cells, promoting the activation of hair matrix cells, inhibiting the expression of hair loss-inducing factors such as DKK-1, etc. The dermal papilla cells of the hair follicle, outer root sheath cells, and hair matrix cells are cells that constitute the hair follicle affecting the thickness and development of hair, and the activation of these cells will affect the hair cycle, and through this mechanism, the effect of improving hair loss can be induced.

[0040] As used herein, the term "promote hair growth" may refer to any action that increases hair growth in hair follicles. For example, it may mean any effect that increases the total amount of hair, such as the effect of promoting hair follicle cell proliferation, hair follicle cell activity, or hair follicle cell growth. Specifically, the hair cycle can be divided into the anagen phase of hair growth, the catagen phase when hair growth ends and the hair bulb shrinks, the telogen phase when the dermal papilla stops functioning and the hair remains on the scalp, and the active phase when the dermal papilla starts to function or generates new hair to cause the old hair to fall out. During the hair cycle, dermal papilla cells are connected to capillaries and sensory nerves and play a role in supplying oxygen and nutrients to hair matrix cells. Hair matrix cells surround the dermal papilla cells and determine the rate of the anagen phase through continuous cell division and proliferation. In addition, outer root sheath cells are located at the part in contact with the basal layer of the epidermis and play a role in protecting the hair before hair keratinization ends.

[0041] According to one embodiment, the peptide exhibits effects such as promoting the proliferation or activation of hair follicle dermal papilla cells, promoting the activation of outer root sheath cells, promoting the activation of hair matrix cells, and inhibiting the expression of hair loss-inducing factors such as DKK-1. Therefore, the peptide can be used as an active ingredient in a cosmetic composition for improving hair loss or promoting hair growth.

[0042] Another aspect of the present invention provides a method for improving damaged hair, a method for improving hair loss, or a method for promoting hair growth, which includes: applying a cosmetic composition containing a peptide having an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient to the skin or hair of an individual.

[0043] Among the terms or technical features mentioned in the description of the cosmetic composition, the same terms or technical features as those already mentioned are as described above.

[0044] As used herein, the terms "apply", "administer", and "apply" can be used interchangeably and may refer to at least partially localizing a composition according to one embodiment at a desired site, or arranging a composition according to one embodiment into an individual through an administration route.

[0045] Another aspect of the present invention also provides a pharmaceutical composition for preventing or treating hair loss, which includes: a peptide having an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

[0046] Among the terms or technical features mentioned in the description of the peptide, the same terms or technical features as those already mentioned are as described above.

[0047] As used herein, the term "prevention" refers to any act of inhibiting or delaying the onset of a disease by administering the composition.

[0048] As used herein, the term "treatment" refers to any form of treatment that provides an effect to an individual suffering from or at risk of a disease, including improving the state of the individual (e.g., at least one symptom), delaying the progression of the disease, delaying the onset of symptoms, or slowing the progression of symptoms, etc. Thus, the terms "treatment" and "prevention" do not imply a cure or complete elimination of symptoms.

[0049] The term "individual" refers to a subject in need of treatment for a disease, more specifically a mammal, such as a human or a non-human primate, a mouse, a dog, a cat, a horse, and a cow, etc.

[0050] The target disease "hair loss" to be prevented or treated by the pharmaceutical composition refers to a state where there is no hair in a part where hair should originally exist. Specifically, it may mean the loss of terminal hair (thick black hair) on the scalp. The causes of hair loss are not limited, but may be caused by various dietary habits and environmental influences such as genetic factors, hormonal imbalance, mental stress, exposure to air pollution, and intake of processed foods. For example, hair loss includes hereditary androgenetic alopecia (baldness), alopecia areata, tinea capitis caused by fungal infection, telogen effluvium, trichotillomania, hair growth disorder diseases, etc., and cicatricial alopecia that forms scars may refer to hair loss caused by lupus, folliculitis decalvans, lichen planopilaris, burns, and trauma.

[0051] According to one embodiment, the peptide exhibits effects such as promoting the proliferation or activation of dermal papilla cells of hair follicles, promoting the activation of outer root sheath cells, promoting the activation of hair matrix cells, and inhibiting the expression of hair loss-inducing factors such as DKK-1. Therefore, the peptide can be used as an active ingredient of a pharmaceutical composition for preventing or treating hair loss.

[0052] As the active ingredient of the pharmaceutical composition, it may include the peptide itself having the above biological activity, derivatives introducing its protecting groups, or peptides extending the terminal region with the amino acid sequence of the peptide as the basic backbone (e.g., 10-mer, 9-mer, 8-mer, 7-mer, 6-mer, 5-mer peptides).

[0053] The pharmaceutical composition may include, but is not limited to, a pharmaceutically effective amount of the peptide; and / or a pharmaceutically acceptable carrier.

[0054] As used herein, the term "pharmaceutically effective amount" may refer to an amount sufficient to achieve the effect of preventing or treating hair loss of the pharmaceutical composition.

[0055] The pharmaceutically acceptable carriers are commonly used in formulations and include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. Suitable pharmaceutically acceptable carriers and formulations are described in detail in "Remington's Pharmaceutical Sciences" (19th Edition, 1995).

[0056] The weight ratio between the peptide and the pharmaceutically acceptable carrier can be, for example, from 500:1 to 1:500. As an example, the weight ratio can be from 450:1 to 1:450, from 400:1 to 1:400, from 350:1 to 1:350, from 300:1 to 1:300, from 250:1 to 1:250, from 200:1 to 1:200, from 150:1 to 1:150, from 100:1 to 1:100, from 80:1 to 1:80, from 60:1 to 1:60, from 40:1 to 1:40, from 20:1 to 1:20, from 10:1 to 1:10, from 8:1 to 1:8, from 6:1 to 1:6, from 4:1 to 1:4, or from 2:1 to 1:2, but is not limited thereto.

[0057] In addition to the above components, the pharmaceutical composition may further include, but is not limited to, lubricants, humectants, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.

[0058] The pharmaceutical composition can be administered orally or parenterally, preferably parenterally. For parenteral administration, it can be carried out by, but is not limited to, intramuscular injection, intravenous injection, subcutaneous injection, intraperitoneal injection, topical administration, transdermal administration, etc.

[0059] The daily dose of the pharmaceutical composition can be, but is not limited to, from 0.0001 μg (microgram) to 1000 μg, from 0.001 μg to 1000 μg, from 0.01 to 1000 μg, from 0.1 to 1000 μg, or from 1.0 μg to 1000 μg, and can be prescribed in various ways according to factors such as formulation method, administration route, patient's age, weight, gender, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity.

[0060] According to methods that can be easily carried out by those skilled in the art, the pharmaceutical composition can be prepared by formulating with pharmaceutically acceptable carriers and / or excipients and in unit dose form or in a multi-dose container.

[0061] The dosage form may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may further include a dispersant and / or a stabilizer.

[0062] Another aspect of the present invention also provides a method for preventing or treating hair loss, which includes: administering to an individual a pharmaceutical composition comprising a peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient in a therapeutically effective amount.

[0063] Among the terms or technical features mentioned in the description of the pharmaceutical composition, the same terms or technical features as those already mentioned are as described above.

[0064] Another aspect of the present invention also provides a food composition for improving damaged hair, preventing hair loss or promoting hair growth, which includes: a peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

[0065] Among the terms or technical features mentioned in the description of the peptide, the same terms or technical features as those already mentioned are as described above.

[0066] The content of the peptide as an active ingredient contained in the food composition can be appropriately selected according to the type of food, desired use, etc. without limitation. For example, it can be added in an amount of 0.01% to 15% by weight of the total weight of the food. In addition, for example, based on 100 ml, the addition ratio of the health drink composition can be 0.02 g to 10 g, preferably 0.3 g to 1 g.

[0067] Beneficial effects

[0068] The peptide according to one aspect can be applied to improving damaged hair, improving hair loss, promoting hair growth, and promoting hair growth, etc. by promoting the proliferation or activation of dermal papilla cells, matrix cells, and outer root sheath cells that make up the hair follicle, and inhibiting the expression of the factor DKK-1 related to hair loss.

[0069] The peptide according to one aspect can be an active ingredient of a composition for improving damaged hair, improving hair loss or promoting hair growth.

[0070] Brief description of the drawings

[0071] Figure 1 Results of confirming the cell proliferation level after adding Peptide-1 according to an embodiment to dermal papilla cells of the hair follicle.

[0072] Figure 2 Results of confirming the cell proliferation level after adding Peptide-2 according to an embodiment to dermal papilla cells of hair follicles.

[0073] Figure 3 Results of confirming the phosphorylation of factors ERK and AKT related to the proliferation of dermal papilla cells of hair follicles after adding Peptide-1 according to an embodiment to dermal papilla cells of hair follicles.

[0074] Figure 4 Results of confirming the phosphorylation of factors ERK and AKT related to the proliferation of dermal papilla cells of hair follicles after adding Peptide-2 according to an embodiment to dermal papilla cells of hair follicles.

[0075] Figure 5 Results of confirming the transfer of β-catenin from the cytoplasm to the nucleus, a factor related to the proliferation of dermal papilla cells of hair follicles, after adding Peptide-1 according to an embodiment to dermal papilla cells of hair follicles.

[0076] Figure 6 Results of confirming the transfer of β-catenin from the cytoplasm to the nucleus, a factor related to the proliferation of dermal papilla cells of hair follicles, after adding Peptide-2 according to an embodiment to dermal papilla cells of hair follicles.

[0077] Figure 7 Results of confirming the expression levels of downstream target genes c-Myc and cyclin D1 of the β-catenin activation mechanism after adding Peptide-1 according to an embodiment to dermal papilla cells of hair follicles.

[0078] Figure 8 Results of confirming the expression levels of downstream target genes LEF-1, c-Myc and cyclin D1 of the β-catenin activation mechanism after adding Peptide-2 according to an embodiment to dermal papilla cells of hair follicles.

[0079] Figure 9 Results of confirming the expression level of the hair loss inducing factor DKK-1 after adding Peptide-1 according to an embodiment to dermal papilla cells of hair follicles.

[0080] Figure 10 Results of confirming the expression level of the hair loss inducing factor DKK-1 after adding Peptide-2 according to an embodiment to dermal papilla cells of hair follicles.

[0081] Figure 11 Results of confirming the expression levels of the outer root sheath cell activators Ha3-II, Keratin 14, and Keratin 19 after adding Peptide-1 according to an embodiment to outer root sheath cells.

[0082] Figure 12 Results of confirming the expression levels of the outer root sheath cell activators Ha3-II, Keratin 5, Keratin 14, and Keratin 19 after adding Peptide-2 according to an embodiment to outer root sheath cells.

[0083] Figure 13 Results of confirming the expression levels of the hair matrix cell activators HOXC13, MSX2, and FOXN1 after adding Peptide-1 according to an embodiment to hair matrix cells.

[0084] Figure 14 Results of confirming the expression levels of the hair matrix cell activators MSX2 and FOXN1 after adding Peptide-2 according to an embodiment to hair matrix cells.

[0085] Figure 15 Results of measuring the tensile strength of human hair over time after applying the composition according to an embodiment (Example 1) to human hair.

[0086] Figure 16 Results of measuring the tensile strength of human hair over time after applying the composition according to an embodiment (Example 2) to human hair.

[0087] Figure 17 Results of taking pictures using a digital camera after applying the composition according to an embodiment (Example 1) to a human hair wig.

[0088] Figure 18 Results of taking pictures using a digital camera after applying the composition according to an embodiment (Example 2) to a human hair wig.

[0089] Figure 19 Results of observing the change in hair roughness (cuticle) over time using an electron microscope after applying the composition according to an embodiment (Example 1) to human hair.

[0090] Figure 20 Results of observing the change in hair roughness (cuticle) over time using an electron microscope after applying the composition according to an embodiment (Example 2) to human hair. Detailed implementation mode

[0091] The present invention will be described in more detail with reference to the embodiments. However, these embodiments are only for exemplarily describing the present invention, and the scope of the present invention is not limited to these embodiments.

[0092] Experimental Example 1, Synthesis of Peptides

[0093] The peptides listed in Table 1 below were synthesized using an automatic peptide synthesizer (Milligen 9050, Millipore, USA), and the synthesized peptides were purified and separated using C18 reversed-phase high performance liquid chromatography (HPLC) (μaters Associates, USA). The chromatographic column used was ACQUITY UPLC BEH300 C18 (2.1 mm X 100 mm, 1.7 μm, WatersCo, USA).

[0094]

Table 1

[0095] Name Sequence (N - terminal → C - terminal) Peptide - 1 RCCG Peptide - 2 EE

[0096] Experimental Example 2, Confirmation of the Effect of Promoting the Proliferation or Activity of Hair Follicle Dermal Papilla Cells

[0097] 2-1. Confirmation of the Effect of Promoting the Proliferation of Hair Follicle Dermal Papilla Cells

[0098] In this experimental example, the effect of the peptide according to an embodiment on the proliferation of human hair follicle dermal papilla cells was confirmed by evaluating the change in the survival rate of human hair follicle dermal papilla cells (HFDPC). Specifically, human hair follicle dermal papilla cells were seeded at 4×10 3After inoculating at a density of cells / well in a 96-well plate, the cells were cultured in mesenchymal stem cell complete media for 24 hours. Then, the medium of the cells was replaced with serum free mesenchymal stem cell complete media and cultured for another 24 hours. Then, peptides according to an embodiment at 500 mM, 5 μM or 50 μM were added respectively and cultured at 37 °C for 72 hours. Next, the cultures were washed with PBS and 10 μL of 5 mg / ml MTT solution was added to each well. The cultures were cultured in a CO2 incubator for 4 hours. After removing the medium, 100 μL of dimethyl sulfoxide (DMSO) was added and stirred for 10 minutes. Then, the absorbance was measured at a wavelength of 540 nm using a spectrophotometer. On the other hand, the untreated group was used as a control group and the group treated with 1 μM EGF was used as a positive control group.

[0099] As a result, as Figure 1 and Figure 2 shown, through the Peptide-1 or Peptide-2, it was confirmed that the proliferation of dermal papilla cells was promoted.

[0100] 2-2. Confirmation of the activation effect of factors related to the proliferation of hair follicle dermal papilla cells

[0101] In this experimental example, the activation effect of the peptide according to an embodiment on factors related to the proliferation of human hair follicle dermal papilla cells was confirmed. Specifically, human hair follicle dermal papilla cells were seeded at 4×10 5Cells were seeded at a density of cells / well in a 6-well plate and cultured in mesenchymal stem cell complete media for 24 hours. Then, peptides according to one embodiment at 500 mM, 5 μM, or 50 μM were added respectively, and the cells were cultured at 37 °C for 24 hours. Then, the cultures were washed with PBS and treated with 100 μL of lysis buffer to prepare cell lysates. Subsequently, Bicinchoninic Acid (BCA) was quantified to prepare equal amounts of protein samples, and then electrophoresis was performed using a 10% SDS-PAGE gel. Next, the proteins separated by the SDS-PAGE were transferred onto a PVDF membrane, and then blocked with 5% skim milk at room temperature for 30 minutes. Then, phospho-AKT and phospho-ERK (Cell Signaling, USA) antibodies were diluted at a ratio of 1:1000 in 3% BSA and reacted with the blocked PVDF membrane at 4 °C for 16 hours. Subsequently, the reaction mixture was washed with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes and repeated 3 times, and the secondary antibody was diluted at a ratio of 1:2000 in 5% skim milk and reacted with the reaction mixture for 1 hour. Next, the reaction mixture was washed with 0.1% PBS-T (0.1% Tween-20 in PBS) for 15 minutes and repeated 3 times, and ECL solution (GE Healthcare, USA) was added, and then the protein expression levels were confirmed. On the other hand, the untreated group was used as a control group, and the group treated with 1 μM Minoxidil was used as a positive control group.

[0102] As a result, as Figure 3 and Figure 4 shown, it was confirmed that Peptide-1 or Peptide-2 induced phosphorylation of ERK and AKT, factors related to the proliferation of dermal papilla cells of hair follicles.

[0103] 2-3. Confirm the effect of the mechanism promoting the proliferation of dermal papilla cells of hair follicles

[0104] In this experimental example, the effect of a peptide according to an embodiment on the proliferation mechanism of human dermal papilla cells was confirmed. Specifically, human dermal papilla cells were cultured in the same manner as in Experimental Example 2-2. After treatment with the peptide according to an embodiment, nuclear proteins were isolated from the culture using a nuclear protein extraction kit (Thermo scientific, USA). Then, using antibodies against β-catenin (cell signaling, USA) and HDAC1 (Santa cruz, USA), the expression levels of the proteins were confirmed in the same manner as in Experimental Example 2-2. On the other hand, the untreated group was used as a control group, and the group treated with 10 ng / mL of recombinant human Wnt-3a protein (rhWnt-3a) (R&D systems (USA, Minnesota)) was used as a positive control group.

[0105] In addition, changes in the levels of downstream target genes, Lymphoid enhancer-binding factor-1 (LEF-1), c-Myc, or cyclin D1, which are caused by the activation mechanism of the β-catenin, were confirmed. For this purpose, human dermal papilla cells were cultured in the same manner as in Experimental Example 2-2 and treated with the peptide according to an embodiment. Subsequently, the culture was washed with PBS, and 300 μL of easy blue (intron, Korea) was treated to isolate RNA. Next, the isolated RNA was quantified using a Nano drop, and then cDNA synthesis was performed on the RNA template using a cDNA synthesis kit (synthesis kit, enzymynomics, Korea). Subsequently, PCR reactions were performed using the primers and PCR premix (PCR premix, enzymynomics, Korea) shown in Table 2 below, and then electrophoresis was performed on a 1.5% agarose gel. Gene expression at the RNA level was confirmed using a Bio-Rad gel image system.

[0106]

Table 2

[0107]

[0108] As a result, as Figure 5 and Figure 6As shown, an increase in the translocation of β-catenin from the cytoplasm to the nucleus was confirmed by the Peptide-1 or Peptide-2. Additionally, as Figure 7 and Figure 8 shown, β-catenin was activated by the Peptide-1 or Peptide-2, and subsequently, the expression of its downstream target genes LEF-1, c-Myc, and / or cyclin D1 increased.

[0109] Experimental Example 3: Confirmation of the effect of inhibiting the expression of hair loss-related factors

[0110] In this experimental example, the effect of the peptide according to an embodiment on the expression of the hair loss-inducing factor DKK-1 (Dickkopf-1) was confirmed. Specifically, human dermal papilla cells were cultured in the same manner as in Experimental Example 2-2, and while adding 500 mM, 5 μM, or 50 μM of the peptide according to an embodiment, a DKK-1 expression-inducing substance, dihydrotestosterone (DHT), was added. Then, using a DKK-1 (Cell Signaling, USA) antibody, the expression level of the protein was confirmed in the same manner as in Experimental Example 2-2. On the other hand, an untreated group was used as a control group, and a group treated with 5 μM finasteride was used as a positive control group.

[0111] As a result, as Figure 9 and Figure 10 shown, it was confirmed that the expression of the hair loss-inducing factor DKK-1 could be inhibited by the Peptide-1 or Peptide-2.

[0112] Experimental Example 4: Confirmation of the effect of promoting the activation of outer root sheath cells

[0113] In this experimental example, the effect of the peptide according to an embodiment on the expression of cytokeratin Ha3-II (type I cuticular Ha3-II), keratin 5, keratin 14, and keratin 19, which are related to the activation of human hair outer root sheath cells (HHORSC), was confirmed. Specifically, human hair outer root sheath cells were seeded at 4×10 5Cells were seeded at a density of cells / well in a 6-well plate and cultured in mesenchymal stem cell complete media for 24 hours. Then, the medium of the cells was replaced with serum-free mesenchymal stem cell complete media and cultured for another 24 hours. Then, peptides according to one embodiment at 500 mM, 5 μM or 50 μM were added respectively and cultured at 37 °C for 24 hours. Subsequently, using the primers in Table 3 below, gene expression at the RNA level was confirmed in the same manner as in Experimental Example 2-3. On the other hand, the untreated group was used as a control group, and the group treated with 50 nM EGF was used as a positive control group.

[0114]

Table 3

[0115]

[0116] As a result, as Figure 11 and Figure 12 shown, through the Peptide-1 or Peptide-2, an increase in the expression of the outer root sheath cell activation factors Ha3-II, Keratin 14, and Keratin 19 was confirmed.

[0117] Experimental Example 5: Confirmation of the effect of promoting hair matrix cell activation

[0118] In this experimental example, the effects of the peptides according to one embodiment on the expression of transcription factors related to the activation of human hair germinal matrix cells (HHGMC), namely Homeobox protein Hox-C13 (HOXC13), Msh homeobox 2 (MSX2), and Forkhead box protein N1 (FOXN1), were confirmed. Specifically, human hair matrix cells were seeded at 4×10 5Cells were seeded at a density of cells / well in a 6-well plate and cultured in mesenchymal stem cell complete media for 24 hours. Then, the media of the cells was replaced with serum-free mesenchymal stem cell complete media and cultured for another 24 hours. Then, peptides according to an embodiment at 500 mM, 5 μM or 50 μM were added respectively and cultured at 37 °C for 24 hours. Subsequently, using the primers in Table 4 below, in the same manner as in Experimental Example 2-3, gene expression at the RNA level was confirmed. On the other hand, an untreated group was used as a control group, and a group treated with 50 nM EGF was used as a positive control group.

[0119]

Table 4

[0120]

[0121] As a result, as Figure 13 and Figure 14 shown, through the Peptide-1 or Peptide-2, increased expression of the hair matrix cell activators HOXC13, MSX2 and FOXN1 was confirmed.

[0122] Experimental Example 6. Preparation of a composition for improving damaged hair

[0123] In this experimental example, a composition for improving damaged hair was prepared, which included a peptide (Peptide-1) according to an embodiment as an active ingredient. Specifically, in a manner known in the art, Composition of Example 1 in the form of a toner was prepared according to the components and contents recorded in Table 5 below. Additionally, in a manner known in the art, Composition of Example 2 in the form of an emulsion was prepared according to the components and contents recorded in Table 6 below.

[0124]

Table 5

[0125]

[0126]

Table 6

[0127]

[0128] Experimental Example 7. Confirmation of the effect of improving the tensile strength of damaged hair

[0129] In this experimental example, the effect of the peptide according to one embodiment on the tensile strength (elasticity) of damaged hair was confirmed. Specifically, 23 subjects were tested. The subjects washed their hair once a day for 3 consecutive days. After drying their hair, the composition of Example 1 or the composition of Example 2 was evenly applied to the hair, and after massaging and combing, it was applied for 5 minutes. Subsequently, hair was collected from the occipital region of the subjects, and the value of the breaking load (BPeak Load, the force intensity when the hair breaks, gmf) changing with time was measured using MTT175 (Miniature Tensile Tester, DiastPon Ltd., UK).

[0130] The results of Example 1 and Example 2 are shown in Table 7 and Table 8 below, respectively. The results of Example 1 and Example 2 for one subject are shown in Figure 15 and Figure 16 . An increase in the breaking load value indicates an improvement in the tensile strength of the hair.

[0131]

Table 7

[0132] Number Before use Immediately after the first use After 3 - day use 1 87.60 115.00 122.00 2 99.30 114.50 162.20 3 75.10 109.30 118.30 4 110.70 118.10 127.00 5 170.00 172.90 202.10 6 102.10 112.70 165.40 7 94.10 115.40 127.50 8 114.70 124.30 130.30 9 123.80 157.90 163.10 10 103.10 128.40 173.70 11 188.60 208.10 222.10 12 149.20 157.60 161.70 13 133.40 142.40 149.10 14 110.70 133.40 161.90 15 115.00 125.60 136.20 16 105.70 126.60 154.20 17 82.30 118.80 160.40 18 109.30 114.90 115.10 19 131.90 143.40 174.30 20 101.80 124.90 137.80 21 102.80 120.50 127.90 22 137.10 140.00 197.10 23 70.20 107.70 115.80 Average 113.85 131.84 152.40 Standard deviation 28.33 23.77 29.03

[0133]

Table 8

[0134] Number Before use Immediately after the first use After 3 - day use 1 128.20 141.40 170.40 2 128.40 131.20 161.70 3 128.00 164.40 167.10 4 104.40 137.90 153.90 5 151.30 152.30 168.60 6 168.80 171.30 198.80 7 131.70 137.60 140.60 8 91.90 109.40 163.80 9 102.60 143.80 178.50 10 105.60 145.00 172.20 11 132.10 138.40 149.90 12 111.40 125.30 174.90 13 157.30 168.80 181.40 14 140.40 148.40 170.90 15 62.10 111.60 160.90 16 67.30 108.70 145.40 17 81.10 128.70 133.40 18 111.00 114.80 125.20 19 110.00 132.30 133.80 20 124.40 146.50 184.60 21 93.80 120.50 158.30 22 143.10 157.40 165.60 23 86.50 110.50 138.40 Average 115.71 136.79 160.80 Standard deviation 27.83 18.92 18.43

[0135] As a result, as shown in Table 7 and Table 8, it was confirmed that when treating the composition of Example 1, the average breaking load value increased by 15.81% immediately after one use and by 33.86% after 3 days of use. When treating the composition of Example 2, it increased by 18.22% immediately after one use and by 38.96% after 3 days of use. There were statistically significant differences (p < 0.001) for both Example 1 and Example 2 compared with before use, whether it was after one use or after 3 days of use.

[0136] Through the above results, it was confirmed that the peptide according to one embodiment has an effect on improving the tensile strength (elasticity) of damaged hair.

[0137] Experimental Example 8. Confirming the effect of improving hair gloss

[0138] In this experimental example, the effect of the peptide according to an embodiment on the glossiness (angel ring) of damaged hair was confirmed. Specifically, 20 human hair wigs were tested. These human hair wigs were washed and dried, and then the composition of Example 1 or the composition of Example 2 was evenly applied to the human hair wigs, followed by massaging, combing, and applying for 5 minutes. Subsequently, a gloss meter (Multi Gloss 268PLUS, Konica Minolta, Japan) was used to measure the gloss unit value at a 60° angle of the gloss meter.

[0139] The results of Example 1 and Example 2 are shown in Table 9 and Table 10 below, respectively. An increase in the gloss unit value indicates an improvement in the gloss of the hair. In addition, Figure 17 and 18 show the digital camera shooting results after applying Example 1 and Example 2 to a human hair wig, respectively.

[0140]

Table 9

[0141] Number Before use Immediately after the first use 1 0.21 0.33 2 0.27 0.31 3 0.24 0.33 4 0.22 0.46 5 0.22 0.39 6 0.23 0.37 7 0.25 0.44 8 0.31 0.50 9 0.20 0.39 10 0.21 0.44 11 0.24 0.50 12 0.19 0.34 13 0.26 0.44 14 0.21 0.46 15 0.19 0.43 16 0.25 0.48 17 0.22 0.42 18 0.24 0.45 19 0.25 0.31 20 0.20 0.45 Average 0.23 0.41 Standard deviation 0.03 0.06

[0142]

Table 10

[0143] Number Before use Immediately after the first use 1 0.24 0.42 2 0.26 0.38 3 0.24 0.49 4 0.21 0.36 5 0.24 0.49 6 0.23 0.42 7 0.25 0.50 8 0.27 0.44 9 0.25 0.51 10 0.25 0.36 11 0.23 0.51 12 0.20 0.41 13 0.23 0.36 14 0.28 0.54 15 0.24 0.36 16 0.27 0.38 17 0.23 0.41 18 0.21 0.50 19 0.23 0.43 20 0.24 0.46 Average 0.24 0.44 Standard deviation 0.02 0.06

[0144] As a result, as shown in Table 9 and Table 10, it was confirmed that when treating the composition of Example 1, the average gloss unit value immediately increased by 78.61% after one use, and when treating the composition of Example 2, it immediately increased by 82.15% after one use. Both Example 1 and Example 2 showed a statistically significant difference (p < 0.001) immediately after one use compared to before use.

[0145] Based on the above results, it was confirmed that the peptide according to an embodiment has an effect on improving the glossiness (angel ring) of damaged hair.

[0146] Experimental Example 9: Confirmation of the effect of improving the roughness of damaged hair

[0147] In this experimental example, the effect of the peptide according to an embodiment on the roughness (cuticle) of damaged hair was confirmed. Specifically, in the same manner as in Experimental Example 7, the composition of Example 1 or the composition of Example 2 was applied to 23 subjects. Then, the hair at the occipital region of the subjects was photographed using a scanning electron microscope (S-4700, Hitachi, Japan) at a magnification of 700 times, and the variable value Ra (μm), which represents the change in the roughness of the hair surface over time, was measured using an image analysis program (Image J, National Institutes of Health, USA).

[0148] The results of Example 1 and Example 2 are shown in Table 11 and Table 12 below, respectively. The decrease in the Ra value indicates an improvement in the hair cuticle and hair roughness. In addition, Figure 19 and Figure 20 show the electron microscope images of a subject after treatment with Example 1 and Example 2, respectively.

[0149]

Table 11

[0150] Number Before use Immediately after the first use After 3 - day use 1 18.40 17.86 14.86 2 20.95 14.96 15.82 3 20.64 14.01 10.65 4 21.48 14.82 10.39 5 25.11 16.22 16.46 6 21.47 20.34 13.72 7 20.86 12.98 10.25 8 22.91 23.45 13.08 9 23.71 20.52 10.81 10 19.02 15.09 11.85 11 21.48 17.30 13.71 12 19.59 13.20 12.07 13 19.76 15.54 14.89 14 20.22 16.76 12.05 15 22.06 19.40 13.45 16 21.12 15.94 17.70 17 18.89 17.93 16.37 18 19.70 14.27 13.14 19 25.64 16.63 17.78 20 21.84 13.01 11.99 21 24.54 23.95 11.88 22 18.48 17.64 12.78 23 17.13 15.99 16.44 Average 21.09 16.86 13.57 Standard deviation 2.20 3.03 2.33

[0151]

Table 12

[0152] Number Before use Immediately after the first use After 3 - day use 1 22.41 19.08 12.64 2 24.32 20.85 17.53 3 27.68 21.12 12.05 4 23.57 17.36 15.69 5 22.99 17.92 13.46 6 24.88 19.32 10.27 7 21.46 20.34 12.21 8 25.94 24.53 19.41 9 20.37 16.12 14.16 10 24.03 17.94 14.84 11 23.53 16.01 14.36 12 21.35 16.77 14.79 13 22.97 14.71 14.76 14 25.93 15.64 15.24 15 27.73 16.11 14.90 16 20.45 13.24 12.06 17 21.74 13.11 10.11 18 23.23 20.60 17.07 19 24.85 19.50 15.49 20 23.62 17.51 15.73 21 20.78 18.41 17.89 22 22.32 16.28 13.33 23 22.72 19.28 16.46 Average 23.43 17.90 14.54 Standard deviation 2.07 2.69 2.34

[0153] As a result, as shown in Table 11 and Table 12, it was confirmed that when treating the composition of Example 1, the average Ra value decreased by 20.04% immediately after one use and by 35.64% after 3 days of use. When treating the composition of Example 2, it decreased by 23.59% immediately after one use and by 37.94% after 3 days of use. There were statistically significant differences (p < 0.001) between Example 1 and Example 2 compared with before use, both immediately after one use and after 3 days of use.

[0154] From the above results, it was confirmed that the peptide according to one embodiment has an effect on improving the roughness (cuticle) of damaged hair.

[0155] Experimental Example 10. Confirmation of the effect of improving the frictional force of damaged hair

[0156] In this experimental example, the effect of the peptide according to one embodiment on the frictional force of damaged hair was confirmed. Specifically, except for using 20 human hair pieces (bleached hair), the composition of Example 1 or the composition of Example 2 was applied to the human hair pieces (bleached hair) in the same manner as in Experimental Example 8. Then, the mean horizontal force out (gmf / mm) value was measured using MTT175 (Miniature Tensile Tester, Diastron Ltd., UK), and the mean horizontal force out value represents the average horizontal frictional force of the hair at the hair root part of the human hair piece (bleached hair).

[0157] The results of Example 1 and Example 2 are shown in Table 13 and Table 14 below, respectively. The decrease in the mean horizontal force out value indicates an improvement in the frictional force of the hair.

[0158]

Table 13

[0159] Number Before use Immediately after the first use 1 96.13 58.63 2 158.20 152.30 3 105.60 97.28 4 101.60 68.30 5 104.00 100.30 6 54.24 37.37 7 118.90 69.48 8 95.70 53.57 9 113.90 70.50 10 113.10 97.47 11 65.53 43.99 12 100.40 49.79 13 100.10 83.20 14 118.10 99.35 15 102.80 62.16 16 87.78 68.73 17 101.70 70.38 18 94.08 59.51 19 109.50 74.54 20 118.70 88.21 Average 103.00 75.25 Standard deviation 20.85 25.91

[0160]

Table 14

[0161] Number Before use Immediately after the first use 1 119.00 64.62 2 117.30 61.97 3 133.20 78.48 4 145.30 115.47 5 75.09 58.23 6 102.50 83.89 7 82.54 65.59 8 136.80 89.77 9 141.50 105.92 10 142.80 119.79 11 128.50 71.38 12 137.60 108.15 13 151.90 124.15 14 152.00 90.77 15 133.50 67.72 16 132.80 99.06 17 127.20 71.85 18 120.90 103.24 19 124.60 65.39 20 128.20 100.90 Average 126.66 87.32 Standard deviation 20.31 21.15

[0162] As a result, as shown in Table 13 and Table 14, when treated with the composition of Example 1, the value of the Mean Horizontal Force Out decreased by 26.94% immediately after one use, and when treated with the composition of Example 2, it decreased by 31.06% immediately after one use. Compared with before use, both Example 1 and Example 2 showed statistically significant differences (p < 0.001) immediately after one use.

[0163] From the above results, it was confirmed that the peptide according to one embodiment has an effect on improving the frictional force of damaged hair.

[0164] Experimental Example 11, Evaluation of Skin Abnormal Reactions

[0165] For the 23 subjects in Experimental Example 7, whether skin abnormal reactions occurred after applying the composition was observed. The results confirmed that no abnormal reactions of allergic contact dermatitis or irritant contact dermatitis occurred. In addition, the subjects were also asked to report erythema (redness), edema (swelling), scale (keratin), itching, stinging (pain), burning sensation, stiffness, and pruritus, and the results confirmed that no skin abnormal reactions were reported.

[0166] From the above results, it was confirmed that the composition containing the peptide according to one embodiment is suitable for skin application.

[0167] Formulation Example 1, Preparation of Peptide Nanobody

[0168] 50 mg of the peptide of Example 1 was fully stirred and dissolved in 500 ml of distilled water. After mixing the ligand solution with 5 g of lecithin, 0.3 ml of sodium oleate, 50 ml of ethanol and a small amount of oil phase, it was made up to 1 L with distilled water, and then emulsified under high pressure using a microfluidizer to prepare a peptide nanobody with a size of about 100 nm.

[0169] Formulation Example 2, Lotion

[0170] A lotion containing the peptide according to one embodiment and composed of the following components was prepared by a method well known in the art.

[0171]

Table 15

[0172] Ingredients Content (wt%) Peptide 1.0 1,3 - butylene glycol 6.0 Glycerin 4.0 PEG 1500 1.0 Steareth - 10 1.0 Polysorbate 20 0.5 Ethanol 8.0 Benzophenone - 9 0.05 Preservative, pigment Appropriate amount Fragrance Appropriate amount Purified water The balance Total 100

[0173] Dosage form Example 3, Nutritional cream

[0174] Using a method well known in the art, a nutritional cream was prepared that includes a peptide according to an embodiment and consists of the following components.

[0175]

Table 16

[0176] Ingredients Content (wt%) Peptide 2.0 Glycerin 10.0 1,3 - butylene glycol 5.0 PEG 1500 2.0 Allantoin 0.1 DL - Panthenol 0.3 EDTA - 2Na 0.02 Hydroxyethyl cellulose 0.1 Sodium hyaluronate 8.0 Carboxy vinyl polymer 0.2 Triethanlamine 0.18 Octyldodecanol - 16 0.4 Ethanol 6 Preservative, pigment Appropriate amount Fragrance Appropriate amount Purified water The balance Total 100

[0177] The above description of the present invention is only for illustration. Those of ordinary skill in the art to which the present invention pertains will understand that it can be easily modified into other specific forms without changing the technical spirit or basic characteristics of the present invention. Therefore, it should be understood that the above embodiments are exemplary in all respects and not restrictive.

Claims

1. A peptide consisting of an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E).

2. The peptide according to claim 1, wherein the N-terminus of the peptide is bound to any one of protecting groups selected from acetyl, fluorenylmethyloxycarbonyl, formyl, palmitoyl, myristoyl, stearoyl, butoxycarbonyl, allyloxycarbonyl, and polyethylene glycol.

3. The peptide according to claim 1, wherein the C-terminus of the peptide is bound to any one of protecting groups selected from amino, tertiary alkyl, and hydrazino.

4. The peptide according to claim 1, wherein the peptide exhibits any one or more 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 hair matrix cells; and (d) Inhibiting the expression of DKK-1.

5. A cosmetic composition for improving damaged hair, comprising: A peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

6. A cosmetic composition for improving hair loss or promoting hair growth, comprising: A peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

7. A pharmaceutical composition for preventing or treating hair loss, comprising: A peptide containing an amino acid sequence represented by Arg(R)-Cys(C)-Cys(C)-Gly(G) or Glu(E)-Glu(E) as an active ingredient.

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