KR102000217B1 - Pharmaceutical composition for preventing or treating hair loss comprising CXCL1 protein and minoxidil - Google Patents

Abstract

The present invention relates to a composition for promoting hair loss, promoting hair growth and promoting hair loss comprising CXCL1 protein and minoxidil as an active ingredient. The CXCL1 protein according to the present invention has no side effects at the time of hair loss treatment and is excellent in hair growth effect even in a short time, so that it can be used not only as a medicine, but also as a quasi-drug, a cosmetic product and a health functional food.

Description

The present invention relates to a pharmaceutical composition for prevention or treatment of hair loss comprising CXCL1 protein and minoxidil as an active ingredient,

The present invention relates to a composition for preventing, treating or improving hair loss comprising a CXCL1 protein and minoxidil as an active ingredient, and a composition for promoting hair growth or hair growth.

Hair loss refers to a state in which there is no hair on the area where the hair normally exists, and generally means that the hair of the scalp (coarse black hair) is removed. The Virgin Mary can cause cosmetic problems when she is out of color and has a different thickness. It is normal for Koreans with low hair density to have about 50-70,000 hairs and about 50-70 hairs per day to be missing. Therefore, if the number of hair that falls out when you sleep or close your hair exceeds 100, hair loss may be ongoing.

The causes of hair loss are diverse. The genetic cause and male hormone, androgen, are thought to be important factors in the occurrence of baldness, and it is presumed that some of them occur in the same path as male pattern hair loss, There are differences in aspects. Alopecia areata is thought to be an autoimmune disease. Alopecia are caused by temporary hair loss caused by severe physical and mental stress such as endocrine diseases, malnutrition, drug use, childbirth, fever, and surgery, and part of the hair does not fill the growth period and falls into the dormant state.

Among the symptoms of such hair loss, male hair loss is a hair loss in a person who has a family history of baldness in the twenties or thirties, and hair loss progresses gradually. The boundary between forehead and head is pushed backward, and the forehead spreads in M-shape on both sides of the temporal region, and hair loss gradually progresses to the parietal region of the head. The hair loss on the forehead is maintained on the forehead as compared with that of the male hair loss, and the hair in the center of the hair is tapered and the hair thinning is reduced. Also, it is rare for feminine hair loss to be completely bald because the degree of hair loss is weak and the forehead peeled off like male hair loss hair loss. In addition, alopecia areata is characterized by the appearance of circular or elliptical depilatory discs of various sizes (hair appears to disappear). It occurs primarily in the head, and rarely occurs in beard, eyebrows and eyelashes, and a large depilation may occur as the symptomatic area enlarges. If the entire hair is lost, it is classified as all-hair alopecia (frontal hair alopecia) and when the whole hair is lost, it is called generalized alopecia. In addition, resting hair alopecia begins 2 ~ 4 months after the onset of the cause of hair loss, hair thinning as a whole is reduced, and if the cause of irritation is removed, resting hair is restored to normal over several months.

As a conventional treatment method for such hair loss, in the case of male or female hair loss, a medicine to be applied such as minoxidil, a medicine to eat such as pinasteride, a hair transplantation and the like are used. In addition, topical steroids, systemic steroids, and immunotherapy are used to treat alopecia universalis. It is important to identify the cause of hair loss and to treat it because the hair is recovered when the cause is removed. However, when treating hair loss by such a conventional method, there is a problem of side effects because it relies on a drug therapy or a steroid preparation, and there is a problem that the speed of treatment is not fast and it is long. In addition, treatment with drugs or hair transplantation has a problem that the treatment cost is greatly increased. Minoxidil and finasteride are representative drugs used to promote hair growth. Minoxidil in the United States can cause side effects such as edema, arrhythmia and hairiness on unwanted areas, and the effects of minoxidil are most effective in 6 months to 1 year after use, The effect is known to be reduced. In addition, finasteride, developed by Merck, is known to inhibit the activity of 5-α-reductase, an enzyme that acts on the male hormone testosterone metabolism in hair follicles, but sexual dysfunction and depression Increased suicidal ideation has been reported. In addition, since it increases the possibility of birth defects, it is not applicable to women in fertility or women during pregnancy. In addition, it is known that if both drugs are discontinued, hair loss will proceed again. In addition, there are valproic acid, but it is known that the child's ability to develop cognition is greatly reduced when taking it during pregnancy. Thus, various conventional hair growth promoting methods have generally been attempted to promote hair growth with the aim of promoting blood circulation and nourishment of hair follicles, but the toxicity and side effects are also severe and the effect thereof is insufficient at present .

KR 10-2016-0100966

Accordingly, the present inventors have made intensive efforts to develop a substance capable of preventing hair loss and promoting hair growth without side effects. As a result, when CXCL1 protein and minoxidil, which have an effect of promoting hair growth, are administered together, And that the hair growth promoting effect is remarkably promoted, and the present invention has been completed.

It is an object of the present invention to provide a pharmaceutical composition for prevention or treatment of hair loss comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

Another object of the present invention is to provide a quasi-drug composition, a cosmetic composition and a food composition for prevention or improvement of hair loss comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition, a quasi-drug composition, a cosmetic composition and a food composition for promoting hair growth or hair growth comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

It is yet another object of the present invention to provide a combined preparation for prevention or treatment of hair loss comprising CXCL1 (C-X-C motif) ligand 1) protein and minoxidil.

In order to achieve the above object, the present invention provides a pharmaceutical composition for prevention or treatment of hair loss comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

In addition, the present invention provides a quasi-drug composition for prevention or improvement of hair loss comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

Also, the present invention provides a cosmetic composition for preventing or improving hair loss comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

The present invention also provides a food composition for preventing or improving hair loss comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

The present invention also provides a pharmaceutical composition for promoting hair growth or hair growth comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

In addition, the present invention provides a quasi-drug composition for accelerating hair growth or hair growth comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

The present invention also provides a cosmetic composition for promoting hair growth or hair growth comprising CXCL1 (chemokine (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

Also, the present invention provides a food composition for promoting hair growth or hair growth comprising CXCL1 (C-X-C motif) ligand 1) protein and minoxidil as an active ingredient.

The present invention also provides a combined preparation for prevention or treatment of hair loss comprising CXCL1 (C-X-C motif) ligand 1) protein and minoxidil.

The composition for promoting hair loss prevention or hair growth comprising the CXCL1 protein and minoxidil as an active ingredient according to the present invention has no side effects at the time of hair loss treatment and is excellent in hair growth effect in a short time due to synergy, Cosmetics and health functional foods.

FIG. 1 is an isometric view of a mouse after 14 days of application of PBS, minoxidil, minoxidil and CXCL1 protein after hair removal using a hair removal agent on C3H / HeN mouse.
FIG. 2 is a graph showing the results of measurement of the hair growth weight (mg) of mice after 14 days from the application of PBS, minoxidil, minoxidil and CXCL1 protein after hair removal using hair removal agents of C3H / HeN mice. Fig.

Hereinafter, the present invention will be described in detail.

The present invention provides a pharmaceutical composition for prevention or treatment of hair loss comprising the CXCL1 protein and minoxidil as an active ingredient, and a pharmaceutical composition for promoting hair growth or hair growth.

CXCL1 (chemokine (C-X-C motif) ligand 1) is a kind of chemokine belonging to the CXC family. Chemokine is a basic heparin-binding low-molecular protein that acts as a leucocyte migration and activation. There are four cysteine residues in the chemokine molecule. Four cysteine residues of CXC (CXCL), CC (CCL), CX3C (CX3CL) and C I have more than one species. The CXCL1 protein is secreted by human melanoma cells, possesses cleavage promoting properties and is implicated in melanoma etiology. CXCL1 protein is expressed in macrophages, neutrophils and epithelial cells and has neutrophil activation function. The CXCL1 protein drives its effect by signaling through the chemokine receptor CXCR2 and is involved in inflammatory reactions, wound healing, and tumorigenesis.

The CXCL1 protein may be composed of all or a part of the peptide having the effect of preventing or treating hair loss, promoting hair growth or hair growth, preferably comprising the amino acid sequence of SEQ ID NO: 1, and functional equivalents and variants .

The functional equivalents of the proteins include proteins and polypeptides that do not totally alter the activity of the protein molecule, and proteins that can function in the same manner are included within the scope of the present invention. The mutant is, for example, one obtained by deletion, substitution or addition of one or several amino acids in the amino acid sequence, 95% or more, preferably 98% or more, and more preferably 99% or more identity with the amino acid sequence And so on. The term "identity" is used herein to mean that, when a gap is introduced into two amino acid sequences or aligned (aligned) so as to have the highest degree of agreement without introducing a gap, the number of amino acid residues in the other amino acid sequence (%) Of the same number of amino acid residues in the amino acid sequence of SEQ ID NO. Refers to an integer of 2 to 10, for example, an integer of 2 to 7, 2 to 5, 2 to 4, and 2 to 3. Specific examples of natural variants include variants based on polymorphisms such as SNP (single base polymorphism), splice variants, and the like. The substitution is preferably a conservative amino acid substitution. And conservative amino acid substitution can have substantially the same structure or properties as human CXCL1 having the above amino acid sequence. Conservative amino acids are amino acids other than nonpolar amino acids (glycine, alanine, phenylalanine, valine, leucine, isoleucine, methionine, proline and tryptophan) and polar amino acids (nonpolar amino acids), charged amino acids (acidic amino acids such as aspartic acid and glutamic acid) (Phenylalanine, tryptophan, tyrosine), branched amino acids (leucine, isoleucine, valine), and aliphatic amino acids (glycine, alanine, leucine), amino acids (arginine, histidine, lysine) and uncharged amino acids (amino acids other than charged amino acids) , Isoleucine, valine) and the like are known. In addition, the protein may include a protein having increased structural stability or increased protein activity due to mutation or modification of the amino acid sequence, such as heat, pH and the like.

The gene encoding the CXCL1 protein may be composed of the nucleotide sequence of SEQ ID NO: 2, and variants capable of functionally equivalent to the nucleotide are included in the scope of the present invention.

As a result of the addition, substitution or deletion of a base, the mutant capable of functionally performing the same function is at least 70% or more, preferably 80% or more, more preferably 90% or more 2, more preferably at least 95%, and is capable of encoding a protein exhibiting substantially the same physiological activity as the protein encoded by the nucleotide sequence shown in SEQ ID NO: 2. For example, although some base sequences have been modified by deletion, substitution or insertion, they include variants that can function in a functionally equivalent manner to the nucleic acid molecule encoding the CXCL1 protein .

The minoxidil is a hair growth inhibitor for preventing or treating hair loss, and is a drug that exhibits a hair growth effect by increasing blood flow in hair roots. However, when applied to the scalp, there is a disadvantage that the drug does not show a great effect if it is not continuously stored in the skin. However, when the CXCL1 protein of the present invention and minoxidil are mixed, hair loss prevention or treatment effect remarkably superior to the hair loss preventive or therapeutic effect confirmed by minoxidil alone administration may be exhibited.

The CXCL1 protein and minoxidil of the present invention can be used in a weight ratio of 1: 1 to 1:20, preferably in a weight ratio of 1: 1 to 1:15, more preferably 1: 1 to 1:10 Can be used. In one specific embodiment of the present invention, a composition comprising a mixture of CXCL1 protein and minoxidil at 1 μg / ml and 10 μg / ml is provided.

As used herein, the term " hair loss ", as used herein, is intended to include without limitation any male hair loss, female hair loss, round hair loss and resting hair loss, May be considered to be hair loss treated or prevented by the composition according to the present invention. Also, the composition according to the present invention has an excellent effect of preventing hair loss before hair loss starts.

As used herein, the term " hair growth " refers to hair growth, and " hair growth " refers to hair growth. The effect of the composition according to the present invention also includes the effect of promoting hair growth or hair growth.

As used herein, the term "prophylactic" means any action that inhibits or delays hair loss by administration of the composition of the present invention, and "treatment" means that the composition of the present invention alleviates or alleviates It means all acts.

The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, Can be used. Suitable formulations known in the art are preferably those disclosed in Remington ' s Pharmaceutical Sciences, Mack Publishing Company, Easton PA.

Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

When the pharmaceutical composition according to the present invention is formulated, it is prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, . In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and suspension include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The composition of the present invention may be administered in a pharmaceutically effective amount.

The term "pharmaceutically effective amount" as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will vary depending on the species and severity, age, sex, The type of drug, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with a conventional therapeutic agent. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art. The preferred dosage of the composition of the present invention will depend on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, and the appropriate total daily dose may be determined by treatment, Generally, an amount of 0.001 to 1000 mg / kg, preferably 0.05 to 200 mg / kg, more preferably 0.1 to 100 mg / kg, can be administered in a single dose, divided into several times a day. Any object can be applied as long as it is an object for prevention or treatment of hair loss, without any particular limitation. But is not limited to, for example, a non-human animal such as a monkey, a dog, a cat, a rabbit, a guinea pig, a rat, a mouse, a cattle, a sheep, a pig,

Meanwhile, the method of administering the pharmaceutical composition according to the present invention is not particularly limited, and it can be administered orally or parenterally, preferably parenterally. When administered parenterally, it can be injected or injected intradermally, subcutaneously, intramuscularly, intravenously, intramuscularly, intraarticularly, intrathecally, intrathecally, intrathecally, preferably subcutaneously, transdermally, Or in the form of application to the site where progression of hair loss is anticipated. In addition, there is no particular limitation on the method of administration, and it is also possible to inject directly into the site where the progress of hair loss or hair loss is predicted. In addition, there is no particular limitation on the method of administration, and it is possible to inject by injecting into the artery or vein. The most preferred administration of the composition of the present invention may be through subcutaneous injection or skin application.

Also, the dosage level selected from the composition will depend upon the activity of the active ingredient, the route of administration, the severity of the hair loss to be treated, and the condition and previous history of the hair loss to be treated. It is, however, within the knowledge of the art to gradually increase the dose until the desired effect is achieved, starting with a dose of the active ingredient at a level lower than that required to achieve the desired therapeutic effect, Sex, body shape, and body weight. The composition may be further processed before being formulated into a pharmaceutically acceptable pharmaceutical formulation and may be preferably ground or ground into smaller particles. Also, the composition will vary depending on the condition and the patient being treated, but it can be determined non-ingeniously.

The compositions of the present invention may be formulated for administration by methods such as direct application or dispensing to the skin, e.g., the hair or scalp, such as, for example, creams, lotions, ointments, aerosols, shampoos, gels, Lt; / RTI > Methods for formulation ingredients and formulations suitable for each formulation are well known in the art. Those skilled in the art can appropriately select and use various formulation ingredients used in the preparation of these external preparations when manufacturing these preparations.

The hair to which the composition of the present invention is applied includes hair follicles and hair follicles, hair and eyelashes and eyelashes, beard, armpits, pubic hair, hair follicles and hair follicles.

 The present invention also provides a pharmaceutical composition for promoting hair growth or hair growth, comprising CXCL1 protein and minoxidil as an active ingredient.

In addition, the present invention provides a quasi-drug composition for prevention or alleviation of hair loss comprising CXCL1 protein and minoxidil as an active ingredient.

Also, the present invention provides a quasi-drug composition for promoting hair growth or hair growth comprising CXCL1 protein and minoxidil as an active ingredient.

The term "quasi-drug" in the present invention means a fiber, a rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or an animal, a weak action on the human body, Or products similar to those which are not machinery, preparations used for sterilization, insecticides and similar uses for the prevention of infections, for the purpose of diagnosis, treatment, alleviation, treatment or prevention of diseases of human beings or animals Machinery, or apparatus, and that is not an apparatus, machine, or apparatus of an article used for the purpose of giving pharmacological effects to the structure or function of a person or animal, It also includes supplies.

When the composition of the present invention is contained in a quasi-drug for the purpose of preventing or ameliorating hair loss or promoting hair growth or hair growth, the composition may be used as it is or may be used in combination with other quasi-drug components, have. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.

The quasi-drug of the present invention is not particularly limited, but may be used in the form of, for example, a cream, a lotion, an aerosol, a shampoo, an gel or a pack.

In the case of a cream, an ointment, a shampoo, a gel, or a pack, it is preferable to use white petrolatum, yellow petrolatum, lanolin, bleached wax, cetanol, stearyl alcohol, stearic acid, hydrogenated oil, Base of; Solvents and dissolution aids such as oleic acid, myristic acid isopropyl, triisooctanoic acid glycerin, crotamiton, diethyl sebacate, diisopropyl adipate, hexyl laurate, fatty acid, fatty acid ester, aliphatic alcohol and vegetable oil; Antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene, and butylhydroxyanisole; Preservatives such as parahydroxybenzoic acid ester; Humectants such as glycerin, propylene glycol and sodium hyaluronate; Surfactants such as polyoxyethylene derivatives, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, and lecithin; Carboxyvinyl polymer, xanthan gum, carboxymethylcellulose, carboxymethylcellulose sodium salt, hydroxypropylcellulose, hydroxypropylmethylcellulose and the like.

In the case of the aerosol preparation, the white petrolatum, the yellow petrolatum, the lanolin, the bleached wax, the cetanol, the stearyl alcohol, the stearic acid, the stearic acid, Base oils such as hydrogenated oils, gelled hydrocarbons, polyethylene glycols, liquid paraffin, squalane and the like; Oleic acid, myristic acid isopropyl, diisopropyl adipate, isobutyl sebacate, glycerin triisooctanoate, crotamiton, diethyl sebacate, hexyl laurate, fatty acid esters, aliphatic alcohols and vegetable oils Solvents and dissolution aids; Antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene, and butylhydroxyanisole; Preservatives such as parahydroxybenzoic acid ester; Humectants such as glycerin, propylene glycol and sodium hyaluronate; Surfactants such as polyoxyethylene derivatives, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, and lecithin; Thickening agents such as carboxyvinyl polymer, xanthan gum, carboxymethyl cellulose, carboxymethyl cellulose sodium salts, hydroxypropyl cellulose, hydroxypropylmethyl cellulose and the like; In addition, various stabilizers, buffers, mating agents, suspending agents, emulsifiers, fragrances, preservatives, solubilizers, and other suitable additives may be added.

In addition, a stabilizer, a preservative, an absorption promoter, a pH adjuster, and other suitable additives may be added as necessary.

The present invention also provides a cosmetic composition for prevention or improvement of hair loss comprising the CXCL1 protein and minoxidil as an active ingredient, and a cosmetic composition for promoting hair growth or hair growth.

The cosmetic composition may be at least one selected from the group consisting of a hair tonic, a hair cream, a hair lotion, a hair shampoo, a hair conditioner, a hair conditioner, a hair spray, a hair aerosol, a pomade, a powder gel, a hair pack, a hair treatment, It may, but is not limited to, be a formulation of a nutrient.

In addition, the composition for preventing or improving hair loss, hair growth or hair growth promotion of the present invention may be used for pets in a different form of the composition. For example, a neutral detergent which can be manufactured in various forms such as a solution shampoo for pet and a rinse for pet such as solution, sol gel, emulsion, oil, wax, and aerosol, and is less irritating to pet skin and excellent in moisture And the like.

In addition, the cosmetic composition of the present invention may include, without limitation, commonly accepted ingredients other than the above-mentioned effective ingredients, and includes conventional auxiliary agents such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances, and carriers can do.

In the case of shampoo, it may contain at least one of a synthetic surfactant, which is a cleaning component, and at least one of preservatives, thickeners, viscosity regulators, pH adjusters, perfumes, dyes, hair conditioning agents and water. Examples of the synthetic anionic surfactant in the synthetic surfactant include alkyl and alkyl ether sulfates, and representative examples thereof include sodium lauryl sulfate, ammonium lauryl sulfate, triethanolamine lauryl sulfate, sodium polyoxyethylene lauryl sulfate, polyoxyethylene lauryl sulfate and the like have. The synthetic amphoteric surfactants in the synthetic surfactants are alkyl betamines and alkylamidopropyl betaines. Representative examples include cocodimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethyl alpha-carboxyethyl betaine , Cetyl dimethyl carboxymethyl betaine, and cocamidopropyl betaine. Examples of the nonionic surfactant include alkanolamides and amine oxides such as lauryldiethylamine oxide, palm oil alkyldimethylamine oxide, lauric acid diethanolamide, palm oil fatty acid diethanolamide, palm oil fatty acid monoethanolamide, and the like.

The optional ingredients used in the present invention are well known to those skilled in the art as conventional optional ingredients for maintaining basic properties and quality as a shampoo. Such optional ingredients include, but are not limited to, pearl wood supplements, preservatives, dyes and viscosity modifiers, pH adjusting agents, perfumes, dyes, and hair conditioning agents. Such as ethylene glycol monostearate and ethylene glycol distearate; Preservatives such as methyl paraoxybenzoate, mixtures of methylchloroisothiazolinone and methyl isothiazolinone; Thickeners and viscosity modifiers such as sodium chloride, ammonium chloride, propylene glycol; PH adjusting agents such as citric acid, phosphoric acid, sodium hydroxide and potassium hydroxide; Hair conditioning agents such as polyquaternium-10, polyquaternium-7, methylpolysiloxane, dimethicone copolyols, hydrolyzed animal proteins, dyes such as water-soluble tar, and perfumes can also be used.

In addition, the present invention provides a food composition for prevention or alleviation of hair loss comprising a CXCL1 protein and minoxidil as an active ingredient, and a food composition for promoting hair growth or hair growth.

The food composition of the present invention may be in the form of a health functional food, and the "health functional food" may be a food prepared or processed by using a raw material or ingredient having a useful function in the human body according to the Health Functional Food No. 6727 , And "functional" means that the structure and function of the human body is ingested for the purpose of obtaining nutritional control, physiological action, and other effects useful for health use.

The above food composition may further include food additives, and the suitability of the food additives as "food additives" is to be determined by the Food and Drug Administration in accordance with the general provisions of the Food Additives Ordinance approved by the Food and Drug Administration, Judge by standards.

Examples of the products listed in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring matter, licorice extract, crystalline cellulose, guar gum, Sodium laurate, sodium glutamate preparation, noodles-added alkaline agent, preservative agent, tar pigment preparation and the like.

Examples of foods containing the active ingredient of the present invention include confectionery ice creams such as bread, rice cake, dried fruits, candy, chocolate, chewing gum and mackerel, ice cream products such as ice cream, ice cream powder, low-fat milk, Dairy products such as processed oil, goat milk, fermented oil, butter oil, concentrated oil, yogurt cream, butter oil, natural cheese, processed cheese, milk powder, milk products, meat products such as hamburger, ham, Fish oil products such as sausage, bacon, etc. Fish products such as instant noodles, dried noodles, fresh noodles, noodle noodles, luxury dried noodles, improved sleep noodles, frozen noodles, noodles such as pasta, vegetable drinks, Seasonings such as bean paste, soybean paste, red pepper paste, chukjang, chonggukjang, mixed berries, vinegar, sauce, tomato ketchup, curry, dressing, margarine, But are the teuning and pizza, without being limited thereto.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

The beverage composition containing the active ingredient of the present invention is not particularly limited to the other ingredients other than those containing the protein, and may contain various flavors or natural carbohydrates such as ordinary beverages as an additional ingredient. Examples of the above-mentioned natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.); Disaccharide, (e.g., maltose, sucrose, etc.); And polysaccharides (for example, dextrin, cyclodextrin and the like), and sugar alcohols such as xylitol, sorbitol and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have.

The present invention also provides a combined preparation for prevention or treatment of hair loss comprising CXCL1 (C-X-C motif) ligand 1) protein and minoxidil.

The combined preparation includes a chemokine (CXC motif) ligand 1) protein and minoxidil as an active ingredient. The CXCL1 protein and minoxidil may be contained in a weight ratio of 1: 1 to 1:20, preferably 1: 1 To 1:15, and more preferably from 1: 1 to 1:10. A specific embodiment of the present invention provides a combination preparation wherein CXCL1 protein and minoxidil are mixed at 1 mu g / ml and 10 mu g / ml.

According to one embodiment of the present invention, the combined preparation produces three times or more new hair as compared with the PBS administration group, so that it can exhibit excellent hair growth promoting effect. This is remarkably higher than the effect of minoxidil alone, and the subcutaneous injection of CXCL1 protein of KR 10-2016-0100966, which is a conventional study, has a remarkably excellent effect Bar and combination preparation, synergistic effect is shown in promoting hair growth and promoting hair growth.

The present invention also provides a method of preventing or treating hair loss comprising treating a subject with CXCL1 protein and minoxidil.

The present invention also provides a method for improving hair loss comprising treating a subject with CXCL1 protein and minoxidil.

Another object of the present invention is to provide a method for promoting hair growth or hair growth comprising treating CXCL1 protein and minoxidil to an individual.

As used herein, the term "prophylactic " means any act that inhibits or delays hair loss by administration of the composition of the present invention, wherein improvement or" treatment "means that the composition of the present invention alleviates, Means any action that is changed.

As used herein, the term " individual " refers to a subject that is likely to progress or progress to hair loss, and is a subject requiring hair growth and hair growth promoting effect. The CXCL1 protein and minoxidil treatment of the present invention may delay, Means an individual whose hair growth can be promoted. Preferably, the subject is a mammal, including a human being.

The term treatment as used herein may include, without limitation, any act of administering and contacting the CXCL1 protein and minoxidil to the subject.

The present invention will be described in more detail with reference to Examples and Experimental Examples. However, the following examples and experimental examples are provided to illustrate the present invention in a more easily understandable manner, and the content of the present invention is not limited by the examples. In this case, , And has a general meaning to those having ordinary skill in the art to which this invention belongs.

Example  One. CXCL1  And Minoxidil  purchase

CXCL1 (Chemokine (C-X-C motif) ligand 1) protein was purchased from Peprotech. The amino acid sequence and DNA base sequence of the obtained CXCL1 protein were analyzed and confirmed, and the results are shown in SEQ ID NO: 1 and SEQ ID NO: 2.

Minoxidil was purchased from Jonhson & Johnson Healthcare USA and purchased 2% (w / v) minoxidil under the trade name "Rogaine".

Example  2. CXCL1  Protein and Minoxidil  Verification of complex hair growth effect

Experiments were conducted to confirm whether hair growth was more effective when minoxidil and CXCL1 protein were used in combination as a therapeutic agent for hair growth. For hair growth regeneration, hair of C3H / HeN mouse at 7 weeks of age was cut short by using a hair removal machine, and hair was completely removed by using a hair removal agent. The hair-removed mice were stabilized for one day and then mixed with recombinant protein CXCL1 at a concentration of 1 μg / ml and 10 μg / ml in 2% Minoxidil (Women's Rogaine, Johnson & Johnson Healthcare Products, USA). A mixture of minoxidil and CXCL1 was applied to the dorsal skin of the epilated mouse every day for 14 days in an amount of 100 mu l. As a control group, a group treated with PBS alone and a group treated with 2% minoxidil alone were set. For 14 days, hair growth in the back of a mouse was traced, and new hair was re-acquired and weighed. The results are shown in FIGS. 1 and 2. FIG.

As shown in Fig. 1, in the case of PBS and minoxidil alone treatment, no hair growth effect was observed in some mice even after 14 days, and new hairy hairs were not found in all of them. However, in the group in which minoxidil and CXCL1 protein were mixed, It was confirmed that effective hair growth effect appeared.

As shown in FIG. 2, the amount of new hair was quantitatively analyzed. As a result, 20 mg of hair was obtained in the PBS alone group and about 30 mg of hair was also obtained in the minoxidil alone group. On the other hand, , And it was confirmed that hair was obtained three times as much as the PBS-treated group and twice as much hair as the minoxidil-treated group. These results indicate that the CXCL1 protein of the present invention alone has a hair growth promoting effect as well as a remarkably superior hair growth promoting effect than the minoxidil hair growth promoting effect when it is administered in combination with minoxidil.

Hereinafter, the pharmaceutical compositions for preventing or treating hair loss, the cosmetic compositions for preventing and alleviating hair loss, and the pharmaceutical compositions containing the active ingredients of the present invention will be described, but the present invention is not limited thereto .

Formulation example  1. Preparation of pharmaceutical preparations

1. Manufacturing of powder

The CXCL1 protein and minoxidil 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

2. Preparation of tablets

The CXCL1 protein and minoxidil 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

3. Preparation of capsules

The CXCL1 protein and minoxidil 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

4. Preparation of injections

The CXCL1 protein and minoxidil 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ 2H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

5. Manufacture of liquids

The CXCL1 protein and minoxidil 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation example  2. Manufacture of cosmetic preparations

1. Hair lotion manufacturing

CXCL1 protein and minoxidil 0.6%

Glycerin 5.1 wt%

Propylene glycol 4.2 wt%

3.0% by weight of tocopheryl acetate

Liquid paraffin 4.6 wt%

1.0% by weight triethanolamine

Squalane 3.1 wt%

Macadamia nut oil 2.5 wt%

Polysorbate 60 1.6 wt%

1.6% by weight of sorbitan sesquiterate

Propyl paraben 0.6 wt%

Carboxyl vinyl polymer 1.5 wt%

Fragrance

Antiseptic

Purified water balance

2. Hair cream production

CXCL1 protein and minoxidil 1.0 wt%

Glycerin 4.0 wt%

Vaseline 3.5 wt%

2.1% by weight triethanolamine

Liquid paraffin 53 wt%

Squalane 3.0 wt%

Wax 2.6 wt%

Tocopheryl acetate 5.4 wt%

Polysorbate 60 3.2 wt%

Carboxyl vinyl polymer 1.0 wt%

3.1 weight percent sorbitan sesquioleate

Fragrance

Antiseptic

Purified water balance

3. Hair shampoo manufacturing

CXCL1 protein and minoxidil 5.8 wt%

35% by weight sodium laureth < RTI ID = 0.0 >

1% by weight of glycerin

3.5% by weight < RTI ID = 0.0 >

1% by weight of propylene glycol

Cocoamidopropyl betaine 1 wt%

Cetyl alcohol 0.1 wt%

0.5% by weight of glycol distearate

8% by weight of butylene glycol

0.2% by weight of methylparaben

0.1% by weight triethanolamine

Citric acid 0.1 wt%

Polyquaternium-7 0.2 wt%

Polycatanium-10 0.12 wt%

Olive oil < SEP > Fiji-7 &

Fragrance

Antiseptic

Purified water balance

Formulation example  3. Manufacture of food preparation

1. Manufacture of health food

CXCL1 protein and minoxidil 100 mg

Vitamin mixture quantity

70 g of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

0.2 g of vitamin B12

Vitamin C 10 mg

Biotin 10 g

Nicotinic acid amide 1.7 mg

Folate 50 g

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2. Manufacture of health drinks

CXCL1 protein and minoxidil 100 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3 g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 L container, ≪ / RTI >

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

<110> SCM Lifescience Co., Ltd <120> Pharmaceutical composition for preventing or treating hair loss          comprising CXCL1 protein and minoxidil <130> SCM1-6P <160> 2 <170> Kopatentin 2.0 <210> 1 <211> 107 <212> PRT <213> Homo sapiens <400> 1 Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu   1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala              20 25 30 Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr          35 40 45 Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser      50 55 60 Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn  65 70 75 80 Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys Ile                  85 90 95 Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn             100 105 <210> 2 <211> 324 <212> DNA <213> Homo sapiens <400> 2 atggcccgcg ctgctctctc cgccgccccc agcaatcccc ggctcctgcg agtggcactg 60 ctgctcctgc tcctggtagc cgctggccgg cgcgcagcag gagcgtccgt ggccactgaa 120 ctgcgctgcc agtgcttgca gaccctgcag ggaattcacc ccaagaacat ccaaagtgtg 180 aacgtgaagt cccccggacc ccactgcgcc caaaccgaag tcatagccac actcaagaat 240 gggcggaaag cttgcctcaa tcctgcatcc cccatagtta agaaaatcat cgaaaagatg 300 ctgaacagtg acaaatccaa ctga 324

Claims (15)

A pharmaceutical composition for prevention or treatment of hair loss comprising CXCL1 (chemokine (CXC motif) ligand 1) protein and Minoxidil as an active ingredient.
The method according to claim 1,
Wherein the CXCL1 protein is composed of the amino acid sequence of SEQ ID NO: 1.
The method according to claim 1,
Wherein the CXCL1 protein is encoded by the polynucleotide of SEQ ID NO: 2.
The method according to claim 1,
Wherein said hair loss is at least one selected from the group consisting of male pattern hair loss, female pattern hair loss, circular hair loss, and resting hair loss.
The pharmaceutical composition for preventing or treating hair loss according to claim 1, wherein the CXCL1 protein is parenterally administered.
The pharmaceutical composition for preventing or treating hair loss according to claim 1, wherein the CXCL1 protein and minoxidil are contained in a weight ratio of 1: 1 to 1:20.
CXCL1 (chemokine (CXC motif) ligand 1) A quasi-composition for prevention or improvement of hair loss comprising a protein and minoxidil as an active ingredient.
CXCL1 (chemokine (CXC motif) ligand 1) A cosmetic composition for prevention or improvement of hair loss comprising a protein and minoxidil as an active ingredient.
CXCL1 (chemokine (CXC motif) ligand 1) protein and minoxidil as an active ingredient.
CXCL1 (chemokine (CXC motif) ligand 1) A pharmaceutical composition for promoting hair growth or hair growth comprising a protein and minoxidil as an active ingredient.
CXCL1 (chemokine (CXC motif) ligand 1) A quasi-drug composition for promoting hair growth or hair growth comprising protein and minoxidil as an active ingredient.
A cosmetic composition for promoting hair growth or hair growth comprising CXCL1 protein and minoxidil as an active ingredient.
A food composition for promoting hair growth or hair growth, comprising CXCL1 protein and minoxidil as an active ingredient.
CXCL1 (chemokine (CXC motif) ligand 1) A combined preparation for prevention or treatment of hair loss comprising a protein and minoxidil.
15. The combination preparation for preventing or treating hair loss according to claim 14, wherein the CXCL1 protein and minoxidil are contained in a weight ratio of 1: 1 to 1:20.

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