KR20220042876A - Composition for preventing or treating hair loss comprising modified egf protein as an active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and a cosmetic composition for preventing hair loss and promoting hair growth or epilation containing a modified EGF protein as an active ingredient, and a pharmaceutical composition, a cosmetic composition and a cosmetic kit for preventing hair loss and promoting hair growth or epilation containing a modified EGF protein and minoxidil as an active ingredient. The modified EGF protein according to the present invention has an effect of preventing or treating hair loss, and furthermore, has an improved effect of preventing hair loss and promoting hair growth or epilation while minimizing the side effects of minoxidil, when administered in combination with minoxidil. Thus, the modified EGF protein alone or together with minoxidil can be advantageously used as a pharmaceutical composition, a cosmetic composition, and a cosmetic kit for preventing hair loss, promoting hair growth or epilation.

Description

A pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein as an active ingredient {COMPOSITION FOR PREVENTING OR TREATING HAIR LOSS COMPRISING MODIFIED EGF PROTEIN AS AN ACTIVE INGREDIENT}

The present invention relates to a pharmaceutical composition, cosmetic composition, and kit for preventing hair loss, promoting hair growth or hair growth, and comprising a modified EGF protein as an active ingredient.

In modern society, hair loss is caused by exposure to environmental pollutants, insufficient nutrition due to excessive dieting, nutritional imbalance and hormone secretion abnormality due to dietary changes, stress due to work and social activities, irregular lifestyle, reckless use of chemical agents, etc. increasing by factors. In particular, as the number of female patients in their 20s and 30s is increasing rapidly and the age of onset is also decreasing, interest in hair loss prevention and treatment is increasing among modern people.

General hypotheses for hair loss known so far are known as dihydrotestosterone theory (DHT, Dihydrotestosterone Theory), gravity theory, blood supply theory, etc., but the exact cause and mechanism of hair loss or hair growth is still unknown. am. Currently, the most commonly used methods for hair loss treatment are autologous hair transplantation in which one's own hair is transplanted, and drug treatment using Minoxidil and Propecia.

The above 　minoxidil was an oral antihypertensive drug, but hirsutism was accidentally observed during a clinical trial, so it was developed as a hair growth drug. Although the mechanism of action of minoxidil is not clearly known, it is explained by hypotheses that it improves blood flow around the scalp hair follicles and induces an increase in blood flow to promote hair growth, and that it directly acts on the epithelium of the hair follicles to induce hair growth. However, when minoxidil is applied to the scalp, it causes breast cancer, itchiness, erythema, dermatitis accompanied by epidermal peeling and dryness, and side effects of causing allergic contact dermatitis and seborrheic dermatitis have been reported in some cases.

Accordingly, the present inventors tried to discover a method capable of preventing hair loss or promoting hair growth or hair growth without side effects. As a result, the modified EGF protein with improved transdermal delivery rate exhibits a hair loss prevention or treatment effect, and when minoxidil is used in combination, only a small amount of minoxidil is excellent in preventing hair loss and promoting hair growth, thereby completing the present invention.

Korean Patent Registration No. 10-2038040

It is an object of the present invention to provide a pharmaceutical or cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein with improved transdermal delivery rate.

Another object of the present invention is to provide a pharmaceutical composition or cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein and minoxidil having improved transdermal delivery rate.

Another object of the present invention is to provide a cosmetic kit for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein with improved transdermal delivery rate and minoxidil.

In order to achieve the above object,

One aspect of the present invention provides a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 as an active ingredient.

Another aspect of the present invention provides a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 and minoxidil as active ingredients.

Another aspect of the present invention provides a cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 as an active ingredient.

Another aspect of the present invention provides a cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 and minoxidil as active ingredients.

Another aspect of the present invention provides a cosmetic kit for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein and minoxidil consisting of the amino acid sequence of SEQ ID NO: 4.

The modified EGF protein according to the present invention exhibits an effect of preventing or treating hair loss, and furthermore, when the modified EGF protein and minoxidil are administered in combination, the side effects of minoxidil are minimized and improved hair loss prevention, hair growth or hair growth promoting effect can be exhibited. . Therefore, the composition comprising the modified EGF protein alone and the composition comprising minoxidil together with the modified EGF protein of the present invention have no side effects even when administered for a long time in chronic hair loss, a chronic disease, and are stable in preventing hair loss, promoting hair growth or hair growth. As it shows efficacy, it can be utilized as a pharmaceutical composition or cosmetic composition/kit for preventing hair loss, promoting hair growth or hair growth.

1 is a result confirming the hair growth promoting effect according to the single administration of the modified EGF protein.
2 is a result confirming the hair growth promoting effect according to the combination of minoxidil and modified EGF protein.

Hereinafter, the present invention will be described in detail.

One aspect of the present invention provides a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 as an active ingredient.

In addition, another aspect of the present invention provides a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 and minoxidil as active ingredients.

As used herein, the term "epidermal growth factor (EGF)" is a protein having a molecular weight of 6 kDa and consisting of 53 amino acids (SEQ ID NO: 1). The EGF is involved in the skin regeneration process by acting on the cell nucleus to promote the division and proliferation rate of epidermal cells. The EGF is used in various ways, such as cosmetics for improving skin condition, wound healing agents, and the like, but has a problem of relatively low wound area delivery and durability.

Meanwhile, the present inventors have developed a modified EGF protein (EGF derivative, hereinafter referred to as "EGF-deri") having the amino acid sequence of SEQ ID NO: 4 with improved in vivo persistence and intracellular permeability. The modified EGF protein may consist of the amino acid sequence of SEQ ID NO: 4. In addition, the gene encoding the modified EGF protein may consist of the nucleotide sequence of SEQ ID NO: 5. In addition, the modified EGF protein may include a signal sequence, which may consist of the amino acid sequence of SEQ ID NO: 2. The modified EGF protein including the signal sequence may be encoded by a gene consisting of the nucleotide sequence of SEQ ID NO: 3.

Furthermore, the present inventors confirmed that the modified EGF protein has significant hair growth promoting activity, and when it is used in combination with minoxidil, an existing hair loss treatment, exhibits an excellent hair growth promoting effect with only a small amount of minoxidil, hair loss of the modified EGF protein The present invention was completed by discovering a novel use for preventing, promoting hair growth or hair growth, and a related use in combination with minoxidil.

The modified EGF protein not only has excellent in vivo delivery and durability, such as transdermal delivery rate compared to standard EGF, but also exhibits a significant hair growth promoting effect, and has the advantage of low protein denaturation rate even under severe conditions. Specifically, standard EGF can be delivered only through the EGF receptor, whereas the modified EGF protein can also be delivered through the FcRn receptor expressed in human hair follicles, so absorption in the pores is improved, thereby exhibiting an excellent hair growth promoting effect.

On the other hand, the modified EGF protein may not be encapsulated in a liposome. Since the protein is difficult to be delivered into the skin, it is common to encapsulate it in liposomes for this purpose, but when the modified EGF protein is not encapsulated in the liposome, it exhibits a superior hair growth promoting effect compared to the case in which the protein is encapsulated in the liposome.

Therefore, the modified EGF protein can increase the skin permeability of the formulation used in combination, and because it has the advantage of easy storage and distribution, it can be very effectively applied to hair loss-related cosmetic compositions and pharmaceutical compositions.

As used herein, the term “minoxidil” is used in a broad sense to include not only minoxidil itself, but also pharmaceutically acceptable derivatives thereof. Suitable derivatives include pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable anhydrides, pharmaceutically acceptable enantiomers, pharmaceutically acceptable esters, and pharmaceutically acceptable derivatives. acceptable polymorphs, pharmaceutically acceptable prodrugs, pharmaceutically acceptable complexes, and the like.

In the composition, the minoxidil may be included in a concentration of 0.5 to 25 mg/ml, 1 to 20 mg/ml, 3 to 15 mg/ml, 5 to 12 mg/ml, about 10 mg/ml. In addition, the daily dose of minoxidil may be 0.25 to 50 mg, 1 to 40 mg, 5 to 30 mg, or 10 to 20 mg. For example, when the minoxidil is a topical composition, it may be used in a dose of less than about 3%, 0.05 to 2.5%, 0.1 to 2%, 0.5 to 2%, or 1 to 1.5%, and applied 1 to 3 times a day It can be administered in the form Minoxidil can exhibit a hair growth effect by increasing blood flow in the hair root, but there is a problem that side effects such as skin irritation such as inflammation, rash, itching, and low blood pressure occur when a large amount is administered. Accordingly, the pharmaceutical composition of the present invention improves the transdermal delivery rate of minoxidil by using the modified EGF protein in combination with minoxidil, so that while using a relatively low concentration of minoxidil as described above, in general, the amount of minoxidil for preventing or treating hair loss. Compared to the case of using a hair loss prevention, hair growth and hair growth promotion effect of equal or higher level can be exhibited.

In addition, the modified EGF protein may be included in a concentration of 0.001 to 0.05 mg/ml, 0.005 to 0.03 mg/ml, 0.007 to 0.02 mg/ml, or about 0.01 mg/ml. For example, the modified EGF protein topical composition at a concentration of 0.005 mg/ml to 0.02 mg/ml may be applied once to 6 times a day, and the amount used may be adjusted according to the degree of hair loss-related lesion. When the EGF protein modified at the above concentration is administered, it exhibits a significant hair growth effect equal to or greater than the equivalent level compared to the case of administering a general hair loss drug, and furthermore, when combined with minoxidil, it can exhibit a synergistic effect in preventing and treating hair loss.

In addition, the modified EGF protein and minoxidil 1: 10 to 1: 25000, 1: 100 to 1: 3000, 1: 300 to 1: 2500, 1: 500 to 1: 2000 or 1: 700 to 1: 1000 of They may be used in combination in a weight ratio. The range of the weight ratio is an optimal ratio that can exhibit excellent hair loss prevention, hair growth or hair growth promoting effect while alleviating or preventing the side effects of minoxidil when the modified EGF protein and minoxidil are used in combination.

The administration method such as the concentration, administration dose, and frequency of administration of each of the modified EGF protein and minoxidil in the composition may be appropriately increased or decreased according to the age, sex, and degree of hair loss of the subject.

As such, by using the modified EGF protein and minoxidil in combination, it is possible to exhibit excellent hair loss prevention or treatment effects while using minoxidil at a concentration lower than that of a general minoxidil drug, and to minimize the side effects caused by minoxidil.

The composition may be in the form of a complex in which the modified EGF protein and minoxidil are mixed. For example, it may be a single formulation prepared by mixing the modified EGF protein and minoxidil with a pharmaceutically acceptable adjuvant, diluent or carrier. In this case, the modified EGF protein and minoxidil may each contain various components within the scope of the corresponding drug. In addition, the single dosage form may be administered together with a separate agent containing other therapeutic agents as a separate dosage form from the dosage form.

In addition, the composition may be in a form in which the modified EGF protein and minoxidil are each formulated and administered simultaneously or sequentially. For example, the modified EGF protein and minoxidil are provided as separate pharmaceutical formulations, and each agent may be administered at the same time or at different times. In this case, the modified EGF protein and minoxidil may be administered simultaneously or alternately, each of which various components are formulated within the scope of the corresponding drug, and may be administered single or multiple.

Specifically, the modified protein and minoxidil may be in different formulations, and independently of each other, may be in the form of skin application, transdermal administration, subcutaneous administration, intradermal administration, oral administration, or intravenous administration. For example, the modified EGF protein may be in a transdermal dosage form, and may be administered once a week to 7 times a week, twice a week to 5 times a week, or 3 times a week. In this case, the minoxidil may be administered orally or in a transdermal dosage form, and the minoxidil may be administered daily, 2 days, 3 days, 4 days, 5 days or 6 days apart, or once a week. The modified EGF protein and minoxidil may be administered independently according to a schedule for each substance.

When the pharmaceutical composition is formulated, it may be prepared using generally used excipients or diluents such as pharmaceutically acceptable fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like. It may also further include anti-aggregating agents, lubricants, flavoring agents, emulsifying agents, preservatives, and the like, using methods well known in the art to provide rapid, sustained, or delayed release of the active ingredient after administration to a mammal. can be formulated.

In addition, the pharmaceutical composition may be formulated as a conventional pharmaceutical formulation known in the art to which the present invention pertains, and preferably may be formulated as a transdermal formulation and a skin external formulation for topical application. Specifically, the composition may be a formulation for external use on the skin selected from formulations of creams, ointments, pastes, gels, patches, jellies, serums, powders, aerosol sprays, non-aerosol sprays, foams, lotions, solutions or suspensions. However, the present invention is not limited thereto.

For example, when the formulation is a paste, cream or gel, animal fiber, vegetable fiber, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as a carrier component. can be used In addition, when the formulation is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane /may contain propellants such as butane or dimethyl ether.

Another aspect of the present invention provides a cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 as an active ingredient.

Another aspect of the present invention provides a cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 and minoxidil as active ingredients.

Here, for the description of the modified EGF protein and minoxidil, refer to the contents previously described in the pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth.

The cosmetic composition may be appropriately selected and formulated by those skilled in the art within a range that does not impair the purpose and effect of the present invention. Examples of ingredients that can be added include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, and blood circulation promoters. , a cooling agent, a limiting agent, purified water, and the like.

In addition, the cosmetic composition may be formulated in a conventional formulation known in the art to which the present invention belongs, hair cream, hair paste, hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, Hair conditioner, hair treatment, hair nutrition cream, hair moisture cream, hair massage cream, hair wax, hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair drying agent, hair preservative, hair dye, It may be prepared in the form of a wave agent for hair, hair bleaching agent, hair gel, hair glaze, hair dresser, hair lacquer, hair moisturizer, hair mousse or hair spray, but is not limited thereto.

Another aspect of the present invention provides a cosmetic kit for preventing hair loss, promoting hair growth or hair growth, comprising the modified EGF protein and minoxidil consisting of the amino acid sequence of SEQ ID NO: 4. Here, for the description of the modified EGF protein and minoxidil, refer to the contents previously described in the pharmaceutical composition for preventing or treating hair loss for preventing hair loss, promoting hair growth or hair growth.

The kit may include a first agent including the modified EGF protein and a second agent including minoxidil. In addition, the first agent and the second agent may be different formulations. Specifically, the kit may include the first agent and the second agent in individually packaged form, and when using the kit, each agent may be utilized according to a separate administration schedule depending on the degree of lesion.

Hereinafter, the present invention will be described in detail by way of Examples. However, the following examples are only illustrative of the present invention, and the content of the present invention is not limited by the following examples.

preparation example 1. Preparation of Samples

preparation example 1.1. deformed EGF protein

A modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 ("EGF-deri") and a modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 encapsulated in liposome ("EGF-deri-Lip", Progen Inc.) ) was used in the experiment. EGF-deri and EGF-deri-Lip were diluted with PBS (pH7.4) buffer to prepare each protein solution at a concentration of 10 ppm (10 ug/ml).

preparation example 1.2. minoxidil

Minoxidil 3% solution (30 mg/ml, Hyundai Pharm) was diluted with minoxidil dilution buffer (50% Ethyl alcohol, 30% Propylene glycol, 20% purified water) to 1% (10 mg/ml) and 0.3% (3 mg) /ml) of minoxidil solution was prepared.

preparation example 2. Preparation of animal models

Seven-week-old C57BL/6 mice from Orient Bio were purchased, and after an adaptation period of one week, the dorsal hairs of 8-week-old female mice were shaved to confirm the resting state of the hair follicles.

Experimental example 1. each substance star Confirmation of hair growth promoting effect

For the mice of Preparation Example 2, the hair growth phase induction effect of the solution according to the composition shown in Table 1 below was evaluated. Three animals were tested in each group, and 0.3ml was applied to the dorsal skin at one time of administration. The first application was performed at the age of 9 weeks, and photos were taken a total of 6 times (day 2, day 8, day 11, day 15, day 18 and day 22) every other day, and the results of hair growth are shown in FIG. 1 .

A1 A2 A3 A4 formulation buffer Minoxidil 3% EGF-deri 10 ug/ml EGF-deri-Lip 10 ug/ml

Referring to FIG. 1 , in the case of group A2 administered with minoxidil, a clear hair growth effect was confirmed. In addition, it can be seen that the A3 group administered with the modified EGF protein of SEQ ID NO: 4 also has a significant hair growth effect. However, in the case of the A4 group of the modified EGF protein of SEQ ID NO: 4 encapsulated in the liposome, the hair growth effect was lower than that of the A1 group.

Experimental example 2. minoxidil and modified EGF Confirmation of hair growth promoting effect according to protein co-administration

In order to confirm the effect of using the modified EGF protein and minoxidil together, the hair growth phase inducing effect of the solution according to the composition shown in Table 2 below was evaluated. When administered once for each group, 0.3 ml was applied to the dorsal skin. The first application was performed at the age of 9 weeks, and the two formulations of each group were alternately applied for 33 days, a total of 10 times (day 1, day 5, day 8, day 12, day 15, day 19, day 22, day 26). , day 29 and day 33) were taken and the results of hair growth are shown in FIG. 2 .

G1 G2 G3 G4 G5 G6 formulation Minoxidil 3%
+ buffer
(Type/Concentration) Minoxidil 1%
+ buffer Minoxidil 0.3%
+ buffer Minoxidil 3%
+ EGF-deri 10 ug/ml Minoxidil 1%
+ EGF-deri 10 ug/ml Minoxidil 0.3%
+ EGF-deri 10 ug/ml n 6 7 6 7 7 6

C57BL/6 mice showed a phenomenon in which the skin color changed to black during the growth phase. Looking at day 8 of FIG. 2, growth phase induction was observed in all mice of the G1 group and the G4 group to which minoxidil 3% was applied. On the other hand, in the G2 group to which only 1% minoxidil was applied, growth phase induction did not start in all mice (n=7), whereas in the G5 group treated with minoxidil 1% and EGF-deri 10 ug/ml every other day, 5 out of 7 mice It was confirmed that vegetative induction begins in In addition, growth phase induction did not start in the mice of the G3 group (n=6) applied with only 0.3% minoxidil, whereas 4 out of 6 mice in the G6 group treated with 0.3% minoxidil and 10 ug/ml of EGF-deri every other day It was observed that vegetative induction begins in

In addition, looking at day 15 of FIG. 2 , it was observed that the hairs of most of the mice in the G1 and G4 groups coated with minoxidil 3% were maintained in the growth phase. On the other hand, in the G2 group, where only 1% of minoxidil was applied, 6 out of 7 mice still did not show any growth phase induction and were induced only in one, whereas minoxidil 1% and EGF-deri 10 ug/ml were treated every other day. In G5, the growth phase was maintained in 5 out of 7 mice, and a phenomenon in which the growth phase induction started was observed in 1 mouse. In addition, in the G3 group to which only 0.3% of minoxidil was applied, growth phase induction started in 2 out of 6 mice, whereas in the G6 group treated with 0.3% minoxidil and 10 ug/ml of EGF-deri every other day, 5 out of 6 mice It was observed that the growth phase was maintained in the animals.

In addition, hair growth in the G1 group applied with minoxidil 3%, the G5 group treated with minoxidil 1% and 10 ug/ml of EGF-deri every other day, and the G6 group treated with 0.3% minoxidil and 10 ug/ml of EGF-deri every other day Since the promoting effect is confirmed at the same level, it can be seen that when a low concentration of minoxidil, which does not produce a hair promoting effect when administered alone, is administered together with the modified EGF protein of the present invention, an excellent hair growth effect appears.

<110> PROGEN CO., LTD. <120> COMPOSITION FOR PREVENTING OR TREATING HAIR LOSS COMPRISING MODIFIED EGF PROTEIN AND MINOXIDIL AS AN ACTIVE INGREDIENT <130> 202009-0029 <160> 5 <170> KoPatentIn 3.0 <210> 1 <211> 53 <212> PRT <213> Artificial Sequence <220> <223> EGF (epidermal growth factor) amino acid sequence <400> 1 Asn Ser Asp Ser Glu Cys Pro Leu Ser His Asp Gly Tyr Cys Leu His 1 5 10 15 Asp Gly Val Cys Met Tyr Ile Glu Ala Leu Asp Lys Tyr Ala Cys Asn 20 25 30 Cys Val Val Gly Tyr Ile Gly Glu Arg Cys Gln Tyr Arg Asp Leu Lys 35 40 45 Trp Trp Glu Leu Arg 50 <210> 2 <211> 323 <212> PRT <213> Artificial Sequence <220> <223> EGF-derivative amino acid sequence <400> 2 Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly 1 5 10 15 Ala Val Phe Val Ser Pro Ser His Ala Asn Ser Asp Ser Glu Cys Pro 20 25 30 Leu Ser His Asp Gly Tyr Cys Leu His Asp Gly Val Cys Met Tyr Ile 35 40 45 Glu Ala Leu Asp Lys Tyr Ala Cys Asn Cys Val Val Gly Tyr Ile Gly 50 55 60 Glu Arg Cys Gln Tyr Arg Asp Leu Lys Trp Trp Glu Leu Arg Arg Asn 65 70 75 80 Thr Gly Arg Gly Gly Glu Glu Lys Lys Gly Ser Lys Glu Lys Glu Glu 85 90 95 Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr Gln 100 105 110 Pro Leu Gly Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 115 120 125 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln 130 135 140 Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val 145 150 155 160 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr 165 170 175 Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 180 185 190 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile 195 200 205 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 210 215 220 Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser 225 230 235 240 Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 245 250 255 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 260 265 270 Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val 275 280 285 Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met 290 295 300 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 305 310 315 320 Leu Gly Lys <210> 3 <211> 969 <212> DNA <213> Artificial Sequence <220> <223> EGF-derivative nucleic acid sequence <400> 3 atggacgcca tgctgagagg cctgtgctgc gtgctgctgc tgtgcggagc cgtgttcgtg 60 agccccagcc acgccaacag cgacagcgag tgccccctga gccacgatgg ctactgcctg 120 cacgatggcg tgtgcatgta catcgaggcc ctggacaagt acgcctgcaa ctgcgtggtg 180 ggctacatcg gcgagaggtg ccagtacaga gacctgaagt ggtgggagct gagaaggaac 240 accggcagag gaggcgagga gaagaaaggc agcaaggaga aggaggagca ggaagagaga 300 gagaccaaga cacccgagtg ccccagccac acccagcccc tgggcgtgtt cctgttccct 360 cccaagccca aagacaccct gatgatcagc agaacacccg aggtgacctg cgtggtcgtg 420 gatgtgagcc aggaagatcc cgaagtgcag ttcaactggt acgtggatgg cgtggaagtg 480 cacaacgcca agaccaagcc cagagaagag cagtcaact ccacctacag agtggtgagc 540 gtgctgaccg tgctgcacca ggactggctg aacggcaagg agtacaagtg caaggtgtcc 600 aacaaaggcc tgcccagctc catcgagaag accatcagca aagccaaagg ccagcccaga 660 gaaccccagg tgtacaccct gcctcccagc caggaagaga tgaccaagaa ccaggtgtcc 720 ctgacctgcc tggtgaaagg cttctacccc agcgacatcg ccgtggagtg ggaaagcaac 780 ggccagcccg agaacaatta caagacaacc cctcccgtgc tggatagcga tggcagcttc 840 tttctgtaca gcagactgac cgtggacaag agcagatggc aggaaggcaa cgtgttcagc 900 tgcagcgtga tgcacgaagc cctgcacaac cactacaccc agaagagcct gtccctgagc 960 ctgggcaag 969 <210> 4 <211> 298 <212> PRT <213> Artificial Sequence <220> <223> EGF-derivative amino acid sequence <400> 4 Asn Ser Asp Ser Glu Cys Pro Leu Ser His Asp Gly Tyr Cys Leu His 1 5 10 15 Asp Gly Val Cys Met Tyr Ile Glu Ala Leu Asp Lys Tyr Ala Cys Asn 20 25 30 Cys Val Val Gly Tyr Ile Gly Glu Arg Cys Gln Tyr Arg Asp Leu Lys 35 40 45 Trp Trp Glu Leu Arg Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys 50 55 60 Gly Ser Lys Glu Lys Glu Glu Gin Glu Glu Arg Glu Thr Lys Thr Pro 65 70 75 80 Glu Cys Pro Ser His Thr Gln Pro Leu Gly Val Phe Leu Phe Pro Pro 85 90 95 Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 100 105 110 Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp 115 120 125 Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 130 135 140 Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 145 150 155 160 His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 165 170 175 Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 180 185 190 Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu 195 200 205 Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 210 215 220 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 225 230 235 240 Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 245 250 255 Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn 260 265 270 Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 275 280 285 Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 290 295 <210> 5 <211> 894 <212> DNA <213> Artificial Sequence <220> <223> EGF-derivative nucleic acid sequence <400> 5 aacagcgaca gcgagtgccc cctgagccac gatggctact gcctgcacga tggcgtgtgc 60 atgtacatcg aggccctgga caagtacgcc tgcaactgcg tggtgggcta catcggcgag 120 aggtgccagt acagagacct gaagtggtgg gagctgagaa ggaacaccgg cagaggaggc 180 gaggagaaga aaggcagcaa ggagaaggag gagcaggaag agagagagac caagacaccc 240 gagtgcccca gccacaccca gcccctgggc gtgttcctgt tccctcccaa gcccaaagac 300 accctgatga tcagcagaac acccgaggtg acctgcgtgg tcgtggatgt gagccaggaa 360 gatcccgaag tgcagttcaa ctggtacgtg gatggcgtgg aagtgcacaa cgccaagacc 420 aagcccagag aagagcagtt caactccacc tacagagtgg tgagcgtgct gaccgtgctg 480 caccaggact ggctgaacgg caaggagtac aagtgcaagg tgtccaacaa aggcctgccc 540 agctccatcg agaagaccat cagcaaagcc aaaggccagc ccagagaacc ccaggtgtac 600 accctgcctc ccagccagga agagatgacc aagaaccagg tgtccctgac ctgcctggtg 660 aaaggcttct accccagcga catcgccgtg gagtgggaaa gcaacggcca gcccgagaac 720 aattacaaga caacccctcc cgtgctggat agcgatggca gcttctttct gtacagcaga 780 ctgaccgtgg acaagagcag atggcaggaa ggcaacgtgt tcagctgcag cgtgatgcac 840 gaagccctgc acaaccacta cacccagaag agcctgtccc tgagcctggg caag 894

Claims (17)

A pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 as an active ingredient.
According to claim 1,
The concentration of the modified EGF protein is 0.001 to 0.05 mg/ml, a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth.
A pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 and minoxidil as active ingredients.
4. The method of claim 3,
The concentration of minoxidil is 0.5 to 25 mg/ml, a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth.
4. The method of claim 3,
The concentration of the minoxidil is 0.05 to 2.5%, hair loss prevention, hair growth or a pharmaceutical composition for promoting hair growth.
4. The method of claim 3,
The daily dose of minoxidil is 0.25 to 50 mg, a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth.
4. The method of claim 3,
The concentration of the modified EGF protein is 0.001 to 0.05 mg/ml, a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth.
4. The method of claim 3,
The modified EGF protein and minoxidil are included in a weight ratio of 1: 10 to 1: 25000, a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth.
4. The method of claim 3,
The composition is a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, in the form of a complex in which the modified EGF protein and minoxidil are mixed.
4. The method of claim 3,
The composition is a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth, wherein the modified EGF protein and minoxidil are each formulated and administered simultaneously or sequentially.
11. The method of claim 10,
The modified EGF protein and minoxidil are different formulations, a pharmaceutical composition for preventing hair loss, promoting hair growth or hair growth.
4. The method of claim 1 or 3,
The composition is an external preparation for skin, cream, ointment, paste, gel, patch, jelly, serum, powder, aerosol spray, non-aerosol spray, foam, lotion, solution or suspension. , A pharmaceutical composition for promoting hair growth or hair growth.
A cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4.
A cosmetic composition for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein consisting of the amino acid sequence of SEQ ID NO: 4 and minoxidil.
A cosmetic kit for preventing hair loss, promoting hair growth or hair growth, comprising a modified EGF protein and minoxidil consisting of the amino acid sequence of SEQ ID NO: 4.
16. The method of claim 15,
The kit is a cosmetic kit for preventing hair loss, promoting hair growth or hair growth, comprising a first agent comprising a modified EGF protein and a second agent comprising minoxidil.
16. The method of claim 15,
The first agent and the second agent are different formulations, a cosmetic kit for preventing hair loss, promoting hair growth or hair growth.

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