KR101810868B1 - Peptides having Hair Growth Activity and Uses Thereof - Google Patents

Abstract

The present invention provides a peptide exhibiting hair growth promoting activity. The peptide of the present invention promotes hair follicle cell growth and exhibits an excellent effect on hair growth by increasing the expression of hair growth related growth factors and hair growth related factors. The peptides of the present invention can be used for preventing or improving hair loss, promoting hair growth, and improving hair growth. In addition, excellent activity and stability of the peptide of the present invention can be applied to quasi-drugs and cosmetics very advantageously.

Description

Peptides having Hair Growth Activity and Uses Thereof}

The present invention relates to a peptide exhibiting hair growth promoting activity and a use thereof.

Hair follicles are unique organs of mammalian skin, where the lower part of the primitive epidermis grows and extends into a deeper layer of skin. At the base of the hair follicle, there is a plug of cells known as follicles or dermal papilla cells (Stenn and Paus, Physiol . Rev., 81: 449 (2002)), and the papilla is the normal circulation of the hair follicle (Oliver, Embryol . Exp . Morph. 15 : 3311 (1966); Oliver, Embryol . Exp . Morph. 16: 231 (1966)) and essential for the growth of hair shafts. The hair shaft is a tread-shaped structure made of tightly adhered epithelial cells filled with keratin filaments and filament aggregation proteins.

Human hair periodically repeats the growth phase, degeneration phase, and resting phase, and the hair goes through the process of being removed and regenerated. The determination of the hair cycle is made through hormonal control or control of many growth factors. On the other hand, hair may undergo a regression period early due to severe stress or nutritional deficiencies, causing severe hair loss ( American Journal of Pathology , 162(3)(2003), (Arck, Petra Clara; Handjiski, Bori). ). In male pattern baldness, the hair follicles on the front and top of the scalp are sensitive to androgens. So, in the case of male pattern baldness, it corresponds to the miniaturization of the hair follicle rather than the destruction of the follicle, which is caused by excessive secretion of the male hormone androgens. Due to the excessive secretion of androgens, 5-alpha reductase is activated and testosterone is transformed into dihydrotestosterone (DHT). The dihydrotestosterone produced in this way shortens the growth period of the hair and reduces the hair follicles to make thick and strong hairs. It causes hair loss by reducing the number.

In general, hair loss spreads with age. For example, different disease states, such as scar alopecia, scarring conditions associated with burns or compression injuries, can cause significant hair loss. To treat such a hair loss phenomenon, various substances have been used as medicines so far, but the price is too high and various side effects are caused. In addition, these drugs require continuous use, and when the use is stopped, hair loss is induced again, individual differences in efficacy are severe, and side effects are also different for each individual.

Other ingredients used in cosmetics have the advantage of being inexpensive, but since they are composed of ingredients derived from plant extracts, their effectiveness is not so great. Therefore, there is a demand in the art for a new active ingredient that is effective and more economical in terms of cost.

Two available drugs known to date (minoxidil and finasteride) may delay further hair loss, but did not induce regeneration of new hair follicles. In addition, among hair cosmetics, many products for preventing hair loss using plant extracts have been released. In particular, products containing extracts such as gosam, red pepper, sugar medicine, sangbaekpi, upper leaves, forest ginseng, licorice, peony, reindeer, fennel, cornus milk, garlic, etc. , A product showing the effect of promoting hair growth by adding a composition containing xanthine and growth hormone to improve the inhibition of cellular metabolism due to excess of dihydrotestosterone, and at the same time, prevent hair loss and regenerate hair by promoting hair growth by growth hormone. , Development of a product containing minerals and vitamins, green tea, rosemary, mugwort, and licorice extract to promote hair growth and hair growth, supplying nutrients to the scalp and hair, preventing hair loss and promoting hair growth. By mixing substances such as promoting products, vitamin B, vitamin C, vitamin D, vitamin E, nicotinic acid, pantothenic acid, biotin and folic acid, and plant extracts, it inhibits 5-alpha reductase in the human body and makes it dihydro in the process of male hormone metabolism. Male-type hair loss products were developed that prevent the formation of testosterone and aid in the metabolism of the hair, but it was difficult to find a product that affects the formation of new hair.

Throughout this specification, a number of papers and patent documents are referenced and citations are indicated. The disclosure contents of the cited papers and patent documents are incorporated by reference in this specification as a whole, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly described.

As a result of trying to develop a peptide having excellent hair growth, the present inventors have selected three kinds of peptides showing excellent hair growth from the peptide library of the present inventors, and have completed the present invention by experimentally identifying their hair growth efficacy. .

Accordingly, an object of the present invention is to provide a peptide that exhibits hair growth promoting activity consisting of one kind of amino acid sequence selected from the group consisting of the amino acid sequences described in SEQ ID NO: 1, 2, and 3 in the Sequence Listing.

Another object of the present invention is to provide a composition for preventing or improving hair loss comprising the peptide as an active ingredient.

Another object of the present invention is to provide a composition for promoting hair growth and improving hair growth, comprising the peptide as an active ingredient.

Other objects and advantages of the present invention will become more apparent by the following detailed description, claims and drawings.

According to one aspect of the present invention, there is provided a peptide exhibiting hair growth promoting activity consisting of one kind of amino acid sequence selected from the group consisting of the amino acid sequences described in SEQ ID NO: 1, 2, and 3 in the Sequence Listing.

As a result of the present inventors trying to develop a peptide having excellent hair growth effect, the present inventors selected three kinds of peptides exhibiting excellent hair growth efficacy from the peptide library of the present inventors, and their hair growth efficacy was experimentally identified.

The peptide of the present invention includes an amino acid sequence selected from the group consisting of amino acid sequences of SEQ ID NOs: 1 to 3 in Sequence Listing. Preferably, the peptide in the present invention consists essentially of an amino acid sequence selected from the group consisting of amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 3.

In the present specification, the term “peptide” refers to a linear molecule formed by bonding of amino acid residues to each other by peptide bonds. The peptides of the present invention are chemically synthesized methods known in the art, in particular solid-phase synthesis techniques; Merrifield, J. Amer . Chem . Soc . 85:2149-54 (1963); Stewart, et al., Solid Phase Peptide Synthesis , 2nd.ed., Pierce Chem. Co.: Rockford, 111 (1984)) or liquid phase synthesis technology (US Patent No. 5,516,891).

The peptides of the present invention are screened for peptides having excellent hair growth efficacy through cell proliferation experiments among the peptide libraries possessed by the present inventors, and a total of 3 types are provided as the peptides of the present invention.

The peptide of the present invention may select a part of the amino acid sequence and induce a modification at the N-terminus or C-terminus in order to increase its activity. Through this modification, the peptide of the present invention can have a high half-life by increasing the half-life when administered in vivo.

In addition, the C-terminus of the peptide of the present invention _{is modified with a hydroxy group (-OH), an amino group (-NH 2} ), an azide (-NHNH ₂ ), and the like, and the N-terminus of the peptide is an acetyl group, a fluorenyl group. A protecting group selected from the group consisting of oxycarbonyl group, formyl group, palmitoyl group, myristyl group, stearyl group and polyethylene glycol (PEG) may be bonded.

The above-described amino acid modification acts to greatly improve the stability of the peptide of the present invention. In the present specification, the term “stability” means not only in vivo stability, but also storage stability (eg, room temperature storage stability). The above-described protecting group functions to protect the peptide of the present invention from attack by protein cleavage enzymes in vivo.

According to an embodiment of the present invention, the peptide of the present invention promotes hair follicle cell growth, increases the expression of β-catenin, a hair growth-related factor, and increases the expression of hair growth-related growth factors KGF, bFGF, and VEGF, Increases the expression of the hair growth signaling molecule PI3K, increases the phosphorylation of ERK, increases the expression of hair growth-related factors MSX2 and karatin-14, inhibits the expression of TGF-β1 related to hair growth delay, and the cell Induces an increase in the expression of Bcl-2, an apoptosis inhibitory protein, and a decrease in the expression of Bax, a cell death-related protein. These results mean that the peptides of the present invention have a very good effect on hair growth. Therefore, the peptide of the present invention can be used for preventing or improving hair loss, promoting hair growth, and improving hair growth.

According to another aspect of the present invention, there is provided a composition for preventing or improving hair loss comprising the peptide of the present invention as an active ingredient.

In the present invention, "prevention of hair loss" means that a phenomenon in which hair is removed from a hair follicle or scalp is prevented or weakened.

The peptide of the present invention induces the proliferation of cells in the hair follicle of the skin tissue, which enables the generation of the hair follicle, so that new hair follicles can be generated. Moreover, by activating a signal of β-catenin, a hair growth promoting gene is expressed, and the expression of growth factors involved in hair growth is increased. This peptide plays a role in promoting the growth period, which is the time when hair is produced and grown, and has the effect of inhibiting hair loss by maintaining the cycle of the hair going to the degenerative period due to various environmental factors, and supplying nutrients to the hair in normal hair. To keep your hair healthy. Therefore, the composition of the present invention is very effective in preventing and improving hair loss.

Since the composition of the present invention contains the peptide of the present invention described above as an active ingredient, descriptions of the contents in common between the two are omitted in order to avoid excessive complexity of the present specification.

According to another aspect of the present invention, there is provided a composition for promoting hair growth and improving hair growth, comprising the peptide of the present invention as an active ingredient.

In the present invention, "promoting hair growth" means that hair is generated, and is used in a broad sense to increase the rate and amount of hair generation. In addition, it means that the number of hairs growing in the hair follicle is increased because the hair root function is strengthened or the period of hair removal and generation is shortened.

In the present invention, "hair growth" means that the thickness of the generated hair (hair) increases or affects the rate of lengthening.

The composition of the present invention can be prepared as a cosmetic composition.

When the composition of the present invention is prepared as a cosmetic composition, a cosmetically effective amount of the peptide of the present invention described above and a cosmetically acceptable carrier may be included.

As used herein, the term “cosmetically effective amount” means an amount sufficient to achieve the efficacy of the composition of the present invention described above.

The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , Oil, powder foundation, emulsion foundation, wax foundation, and may be formulated as a spray, but is not limited thereto. In more detail, it may be prepared in the form of a flexible lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as a carrier component. I can.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane / May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and crystallites Sex cellulose, aluminum metahydroxide, bentonite, agar or tracanth, and the like can be used.

When the formulation of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters may be used.

The ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions, in addition to peptides and carrier ingredients as active ingredients, such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances. Phosphorus adjuvants may be included.

The features and advantages of the present invention are summarized as follows:

(a) The present invention provides a peptide exhibiting hair growth promoting activity.

(b) The peptide of the present invention promotes hair follicle cell growth and exhibits excellent effects on hair growth by increasing the expression of hair growth-related growth factors and hair growth-related factors.

(c) The peptide of the present invention can be used for preventing or improving hair loss, promoting hair growth, and improving hair growth.

(d) The excellent activity and stability of the peptide of the present invention described above makes it possible to be applied very advantageously to quasi-drugs and cosmetics.

The features and advantages of the present invention are summarized as follows:
(a) The present invention provides a peptide exhibiting hair growth promoting activity.
(b) The peptide of the present invention promotes hair follicle cell growth and exhibits excellent effects on hair growth by increasing the expression of hair growth-related growth factors and hair growth-related factors.
(c) The peptide of the present invention can be used for preventing or improving hair loss, promoting hair growth, and improving hair growth.
(d) The excellent activity and stability of the peptide of the present invention described above makes it possible to be applied very advantageously to quasi-drugs and cosmetics.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for describing the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

Example

Synthesis Example 1: Synthesis of Peptide

700 mg of chloro trityl chloride resin (CTL resin, Nova biochem Cat No. 01-64-0021) was placed in a reaction vessel, and 10 ml of methylene chloride (MC) was added, followed by stirring for 3 minutes. The solution was removed, 10 ml of dimethylformamide (DMF) was added, stirred for 3 minutes, and the solvent was removed again. 10 ml of dichloromethane solution was added to the reactor, 200 mmole of Fmoc-Ile-OH (Bachem, Swiss) and 400 mmole of diisopropyl ethylamine (DIEA) were added, followed by stirring to dissolve well, and reacting with stirring for 1 hour. After the reaction was washed, methanol and DIEA (2:1) were dissolved in DCM (dechloromethane), reacted for 10 minutes, and washed with an excess of DCM/DMF (1:1). The solution was removed, 10 ml of dimethylformamide (DMF) was added, stirred for 3 minutes, and the solvent was removed again. 10 ml of a deprotection solution (20% piperidine/DMF) was added to the reaction vessel and stirred at room temperature for 10 minutes, and then the solution was removed. The same amount of deprotection solution was added and the reaction was maintained for another 10 minutes, and then the solution was removed and washed twice with DMF, once with MC, and once with DMF for 3 minutes each to prepare Ile-CTL Resin. 10 ml of DMF solution was added to a new reactor, 200 mmole of Fmoc-Lys(Boc)-OH (Bachem, Swiss), 200 mmole of HoBt, and 200 mmole of Bop were added, followed by stirring to dissolve well. After adding 400 mmole DIEA to the reactor twice as a fraction, the mixture was stirred for at least 5 minutes until all solids were dissolved. The dissolved amino acid mixture solution was placed in a reaction vessel with a deprotected resin and reacted with stirring at room temperature for 1 hour. The reaction solution was removed, and the mixture was stirred 3 times for 5 minutes with a DMF solution, and then removed. A small amount of reaction resin was taken and the degree of reaction was checked using a Kaiser test (Nihydrin Test). Lys(Boc)-Ile-CTL Resin was prepared by performing a deprotection reaction twice in the same manner as above with a deprotection solution. After sufficiently washing with DMF and MC, performing the Kaiser test again, the following amino acid adhesion experiment was performed in the same manner as above. Based on the selected amino acid sequence, a chain reaction was carried out in the order of Fmoc-Arg(Pbf)-OH and Fmoc-Arg(Pbf)-OH. The Fmoc-protecting group was reacted twice with a deprotection solution for 10 minutes each, and then washed well and removed. After performing acetylation for an hour by adding acetic anhydride, DIEA, and HoBt, the prepared peptidyl resin was washed three times with DMF, MC and methanol, respectively, and dried by slowly flowing nitrogen air, and then P ₂ O ₅ After drying completely under vacuum under reduced pressure, 30 ml of a desulfurization solution [Trifluroacetic acid 95%, distilled water 2.5%, Thioanisole 2.5%] was added, and the reaction was allowed to react for 2 hours with occasional shaking at room temperature. Maintained. The resin was filtered by filtering, and the resin was washed with a small amount of TFA solution and then combined with the mother liquor. After distillation using reduced pressure so that the total volume remains about half, 50 ml of cold ether was added to induce precipitation, and then the precipitate was collected by centrifugation, followed by washing with cold ether twice. The mother liquor was removed and sufficiently dried under nitrogen to synthesize 0.7 g of Arg-Arg-Lys-Ile peptide 1 before purification (yield: 90.0%). When measured using a molecular weight analyzer, a molecular weight of 571.7 (theoretical value: 571.72) could be obtained. Other SEQ ID NO: 2 and SEQ ID NO: 3 peptides were also synthesized in the same manner as above.

number Amino acid sequence Analysis value (mass spectrometer) Analysis value Theoretical value SEQ ID NO: 1 (peptide-1) Arg-Arg-Lys-Ile 571.7 571.72 SEQ ID NO: 2 (peptide-2) Ile-Tyr-Phe-Tyr 604 604.7 SEQ ID NO: 3 (peptide-3) Lys-Lys-Phe-Ile-Gln-Gln-Val-Tyr-Leu-Ala-Ile 1350.6 1350.65

In order to secure peptides showing the hair growth promoting effect, the company's peptide library screening was conducted through cell proliferation experiments, and three kinds of peptides were selected. Afterwards, the hair growth promoting efficacy of these three peptides was observed through changes in expression of various genes and proteins below, and their excellent efficacy was confirmed.

Example 1: DPC proliferation assay

Human hair follicle dermal papilla cells were seeded in a 96-well plate at a density of ^{2×10 3 cells/well and cultured overnight.} After changing to a serum-free medium, the peptide was treated and cultured for 3 days, and 100 μl of 4 mg/ml MTT solution was treated in the wells and reacted for 4 hours. After dissolving the generated formazan through DMSO treatment, the absorbance at 560 nm was measured using a microplate reader.

As a result, it was confirmed that the growth of human dermal papilla cells was promoted in a concentration-dependent manner by treatment with the peptides of the first sequence, the second sequence, or the third sequence (FIGS. 1a-c).

Example 2: β-catenin activation test

Human dermal papilla cells were seeded in a 6-well plate at a density of ^{4×10 5 cells/well and cultured overnight.} After changing to a serum-free medium, peptides were treated, cultured for 15 and 30 minutes, and cells were recovered to separate nuclei and cytoplasmic proteins, respectively. Western blotting was performed using a β-catenin antibody (santacruz biotechnology, USA) to compare the expression patterns of β-catenin in the nucleus.

As a result, it was observed that nuclear translocation according to the increase in the activity of β-catenin, a factor related to hair growth in human dermal papilla cells, is promoted by treatment with a peptide of SEQ ID NO: 1, 2 or 3 ( Figures 2a-c).

Example 3: KGF, bFGF, VEGF RT-PCR

Human dermal papilla cells were seeded in a 6-well plate at a density of ^{4×10 5 cells/well and cultured overnight.} After changing to a serum-free medium, the peptide was treated and cultured for 24 hours, and the cells were recovered and RNA was isolated. After RNA quantification, cDNA was synthesized using a cDNA synthesis kit (Intron, Korea), and PCR was performed using a PCR premix (Intron, Korea) and primers of KGF, bFGF, and VEGF, followed by electrophoresis on a 5% agarose gel. The levels of mRNA expression of the growth factors were compared under the sample treatment conditions.

primer Sequence (5’-3’) KGF forward direction TCTGTCGAACACAGTGGTACCT KGF reverse GTGTGTCCATTTAGCTGATGCAT bFGF forward TGCTGGTGATGGGAGTTGTA bFGF reverse CCTCCAAGTAGCAGCCAAAG VEGF forward CCATGAACTTTCTGCTGTCTT VEGF reverse TCGATCGTTCTGTATCAGTCT

As a result of the experiment, it was confirmed that mRNA expression of KGF and bFGF, which are growth factors related to hair growth, was increased in human dermal papilla cells by treatment with the peptide of Sequence Listing 1 (FIG. 3A).

In addition, mRNA expression of VEGF, a factor affecting hair growth in human dermal papilla cells, was increased by treatment with the sequence listing 2 peptide (Fig. 3b), and mRNA expression of VEGF and bFGF by the treatment with the sequence listing 3 peptide It was confirmed that this increase (Fig. 3c).

Example 4: PI3K & p-ERK WB

Human dermal papilla cells were seeded in a 6-well plate at a density of ^{4×10 5 cells/well and cultured overnight.} After changing to a serum-free medium, the peptide was treated and cultured for 15 to 30 minutes, and cells were recovered to prepare a cell lysate. Western blotting was performed using PI3K antibody (santacruz biotechnology, USA) and phospho-ERK antibody (Cell Signaling Technology, USA) to compare protein expression patterns.

As a result, an increase in the expression of PI3K, a hair growth signaling molecule, and an increase in ERK phosphorylation were observed in human dermal papilla cells by treatment with the peptide of the first sequence or the third sequence in the sequence listing (FIGS. 4a-b).

Example 5: MSX2 RT-PCR

Human dermal papilla cells were seeded in a 6-well plate at a density of ^{4×10 5 cells/well and cultured overnight.} After changing to a serum-free medium, the peptide was treated and cultured for 24 hours, and the cells were recovered and RNA was isolated. After RNA quantification, cDNA was synthesized using a cDNA synthesis kit (Intron, Korea), and PCR was performed using PCR premix (Intron, Korea) and MSX2 primers, followed by electrophoresis on 5% agarose gel to express mRNA under each sample processing condition. The degree was compared.

primer Sequence (5’-3’) MSX2 forward direction AACACAAGACCAACCGGAAG MSX2 reverse GCAGCCATTTTCAGCTTTTC

As a result, it was confirmed that the mRNA expression of the hair growth-related factor MSX2 was promoted in human dermal papilla cells by the treatment of the peptide of the second or third sequence in the sequence listing (Figs. 5a-b).

Example 6: TGF-β1 RT-PCR

Human dermal papilla cells were seeded in a 6-well plate at a density of ^{4×10 5 cells/well and cultured overnight.} After changing to a serum-free medium, the peptide was treated and cultured for 24 hours, and the cells were recovered and RNA was isolated. After RNA quantification, cDNA was synthesized using a cDNA synthesis kit (Intron, Korea), and PCR was performed using a PCR premix (Intron, Korea) and TGF-β1 primer, followed by electrophoresis on a 5% agarose gel. The level of mRNA expression was compared.

primer Sequence (5’-3’) TGF-β1 forward direction GCCCTGGATACCAACTATTGC TGF-β1 reverse TCAGCACTTGCAGGAGTAGCG

As a result, it was confirmed that the mRNA expression of TGF-β1 related to hair growth delay in human dermal papilla cells was suppressed by the peptide treatment of the first sequence or the second sequence (FIGS. 6a-b).

Example 7: Bcl-2/Bax WB

Human dermal papilla cells were seeded in a 6-well plate at a density of ^{4×10 5 cells/well and cultured overnight.} After changing to a serum-free medium, the peptide was treated and cultured for 24 hours, and cells were recovered to prepare a cell lysate. Western blot was performed using Bcl-2 and Bax antibodies (santacruz biotechnology, USA) to compare protein expression patterns.

As a result, it was confirmed that the expression of the apoptosis inhibitory protein Bcl-2 and the apoptosis-related protein Bax decreased in human dermal papilla cells by treatment with the peptide of SEQ ID NO: 1 or 3 (Fig. 7a-b). ).

Example 8: Keratin-14 RT-PCR

Human dermal papilla cells were seeded in a 6-well plate at a density of ^{5×10 5 cells/well and cultured overnight.} After changing to a serum-free medium, the peptide was treated and cultured for 24 hours, and the cells were recovered and RNA was isolated. After RNA quantification, cDNA was synthesized using a cDNA synthesis kit (Intron, Korea), and PCR was performed using a PCR premix (Intron, Korea) and keratin-14 primer, followed by electrophoresis on a 5% agarose gel. The level of mRNA expression was compared.

primer Sequence (5’-3’) Keratin-14 forward CCACCTTTCATCTTCCCAATTCTC Keratin-14 reverse GTGCGGATCTGGCGGTTG

As a result, it was confirmed that mRNA expression of keratin-14, a hair growth-related factor, was increased in human dermal papilla cells by treatment with the peptide of SEQ ID NO: 1 (FIG. 8).

As described above, specific parts of the present invention have been described in detail, and for those of ordinary skill in the art, it is clear that these specific techniques are only preferred embodiments, and the scope of the present invention is not limited thereto. Therefore, it will be said that the practical scope of the present invention is defined by the appended claims and their equivalents.

<110> CAREGEN CO., LTD. <120> Peptides having Hair Growth Activity and Uses Thereof <130> PN160021D2 <160> 15 <170> KopatentIn 2.0 <210> 1 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Peptide 1 <400> 1 Arg Arg Lys Ile One <210> 2 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Peptide 2 <400> 2 Ile Tyr Phe Tyr One <210> 3 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Peptide 3 <400> 3 Lys Lys Phe Ile Gln Gln Val Tyr Leu Ala Ile 1 5 10 <210> 4 <211> 22 <212> DNA <213> KGF Forward Primer <400> 4 tctgtcgaac acagtggtac ct 22 <210> 5 <211> 23 <212> DNA <213> KGF Reverse Primer <400> 5 gtgtgtccat ttagctgatg cat 23 <210> 6 <211> 20 <212> DNA <213> bFGF Forward Primer <400> 6 tgctggtgat gggagttgta 20 <210> 7 <211> 20 <212> DNA <213> bFGF Reverse Primer <400> 7 cctccaagta gcagccaaag 20 <210> 8 <211> 21 <212> DNA <213> VEGF Forward Primer <400> 8 ccatgaactt tctgctgtct t 21 <210> 9 <211> 21 <212> DNA <213> VEGF Reverse Primer <400> 9 tcgatcgttc tgtatcagtc t 21 <210> 10 <211> 20 <212> DNA <213> MSX2 Forward Primer <400> 10 aacacaagac caaccggaag 20 <210> 11 <211> 20 <212> DNA <213> MSX2 Reverse Primer <400> 11 gcagccattt tcagcttttc 20 <210> 12 <211> 21 <212> DNA <213> TGF-beta1 Forward Primer <400> 12 gccctggata ccaactattg c 21 <210> 13 <211> 21 <212> DNA <213> TGF-beta1 Reverse Primer <400> 13 tcagcacttg caggagtagc g 21 <210> 14 <211> 24 <212> DNA <213> Keratin-14 Forward Primer <400> 14 ccacctttca tcttcccaat tctc 24 <210> 15 <211> 18 <212> DNA <213> Keratin-14 Reverse Primer <400> 15 gtgcggatct ggcggttg 18

Claims (9)

A peptide having the hair growth promoting activity comprising the amino acid sequence of SEQ ID NO: 3. The peptide of claim 1, wherein the peptide promotes hair cell growth. 2. The peptide of claim 1, wherein the peptide increases the expression of beta -catenin. 2. The peptide of claim 1, wherein the peptide increases expression of a hair growth-related growth factor selected from the group consisting of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). 2. The peptide of claim 1, wherein the peptide increases the expression of MSX2 (Msh homeobox 2). The peptide according to claim 1, wherein the peptide increases expression of PI3K (Phosphoinositide 3-kinase) and ERK (Extracellular Signal-regulated Kinase) phosphorylation.  The peptide according to claim 1, wherein the peptide increases the expression of Bcl-2 (B-cell lymphoma 2) and decreases the expression of Bax (BCL2-associated X protein). A composition for preventing or improving hair loss comprising the peptide of any one of claims 1 to 7 as an active ingredient. A composition for promoting hair growth and hair growth, comprising the peptide of any one of claims 1 to 7 as an active ingredient.

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