WO2018030683A1 - Pharmaceutical composition comprising thymidine phosphorylase (tymp) protein as effective ingredient for prevention or treatment of hair loss - Google Patents

Pharmaceutical composition comprising thymidine phosphorylase (tymp) protein as effective ingredient for prevention or treatment of hair loss Download PDF

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WO2018030683A1
WO2018030683A1 PCT/KR2017/008117 KR2017008117W WO2018030683A1 WO 2018030683 A1 WO2018030683 A1 WO 2018030683A1 KR 2017008117 W KR2017008117 W KR 2017008117W WO 2018030683 A1 WO2018030683 A1 WO 2018030683A1
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Prior art keywords
hair
hair loss
protein
tymp
composition
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PCT/KR2017/008117
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French (fr)
Korean (ko)
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송순욱
성종혁
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에스씨엠생명과학 주식회사
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Publication of WO2018030683A1 publication Critical patent/WO2018030683A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/18Peptides; Protein hydrolysates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/30Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat

Definitions

  • the present invention is a pharmaceutical composition for preventing or treating hair loss, a composition for preventing or improving hair loss, a composition for preventing or improving hair loss, a composition for promoting hair growth or promoting hair loss, a method for preventing or treating hair loss, a method for improving hair loss, and a hair growth comprising a thymidine phosphorylase (TYMP) protein as an active ingredient It is about hair growth promotion method.
  • TYMP thymidine phosphorylase
  • Hair loss refers to a condition in which hair is not normally present in the area where hair is normally present, and generally means that the hair of the scalp (coarse black hair) falls out. Unlike virgin hair, which has no color and thick color, it can cause cosmetic problems if it falls out. Koreans with lower hair density than Westerners have 5-70,000 hairs, and about 50-70 hairs per day are normal. Therefore, hair loss may be in progress if the number of hairs that fall after sleeping or when you wash your hair exceeds 100.
  • Alopecia areata is thought to be an autoimmune disease. Resting alopecia is a temporary hair loss that occurs after severe physical and mental stress such as endocrine disease, nutritional deficiency, drug use, childbirth, fever, and surgery.
  • male-type hair loss is gradually thinning hair from the 20s or 30s in people with a family history of baldness, hair loss proceeds.
  • the forehead and head line is pushed backward, the forehead widens in the M-shape with both temporal heads and hair loss progresses gradually in the crown of the head.
  • Female hair loss is characterized in that the hairline on the forehead is thinned and hair thinner compared to male hair loss.
  • female hair loss is so weak that hair loss is rare and complete baldness, as in male hair loss.
  • Alopecia areata is also characterized by the development of round or oval bald spots of varying sizes (hair loss that looks like dots).
  • alopecia areata frontal alopecia
  • hair thinning is reduced overall. As the causative stimulus is removed, hair loss is reduced as restorative hair returns to normal for several months.
  • a male or female hair loss drug such as minoxidil, a drug such as finasteride, a hair transplant, and the like are used.
  • alopecia topical steroid preparations, systemic steroid preparations, immunotherapy and the like are used. Resting alopecia causes hair to recover when the cause is removed, so it is important to identify and treat the cause.
  • alopecia causes hair to recover when the cause is removed, so it is important to identify and treat the cause.
  • there is a problem of side effects because it depends on drug therapy, steroid preparations, etc.
  • the treatment cost also increases significantly if the treatment using drugs or hair transplantation.
  • Minoxidil and finasteride are representative drugs used to promote hair growth.
  • Minoxidil from the US Upzone may cause side effects such as swelling, arrhythmia and unwanted hairs on long term application.
  • the effect of minoxidil is most effective between 6 months and 1 year from use and then gradually It is known that the effect is reduced.
  • Finasteride developed by Merck, is known to inhibit the activity of 5- ⁇ -reductase, an enzyme that acts on male hormone testosterone metabolism in hair follicles. An increase in suicidal thoughts has been reported.
  • it is not applicable to women of childbearing age or pregnant women because it increases the probability of birth of birth defects.
  • hair loss progresses again if both drugs are discontinued.
  • Valproic acid but taking it during pregnancy is known to greatly reduce the child's cognitive development ability.
  • various types of conventional hair regrowth have been attempted to help hair growth for the purpose of promoting blood circulation of the scalp and nourishing hair roots.
  • the present invention is also toxic and side effects are severe and the effect is insufficient. .
  • the present inventors have made intensive efforts to develop a material capable of preventing hair loss and promoting hair growth without side effects, and confirmed that the TYMP (thymidine phosphorylase) protein present in the body has an effect of promoting hair growth. Completed.
  • TYMP thymidine phosphorylase
  • Another object of the present invention is to provide a quasi-drug composition, cosmetic composition and food composition for preventing or improving hair loss containing TYMP protein as an active ingredient.
  • Another object of the present invention to provide a pharmaceutical composition, quasi-drug composition, cosmetic composition and food composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • Still another object of the present invention is to provide a method for preventing or treating hair loss, a method for improving hair loss, and a method for promoting hair growth or hair growth, comprising: treating a subject with TYMP protein.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of hair loss comprising TYMP (thymidine phosphorylase) protein as an active ingredient.
  • TYMP thymidine phosphorylase
  • the present invention provides a quasi-drug composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
  • the present invention also provides a cosmetic composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
  • the present invention provides a food composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
  • the present invention provides a pharmaceutical composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • the present invention provides a quasi-drug composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • the present invention also provides a cosmetic composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • the present invention provides a food composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • the present invention also provides a method for preventing or treating hair loss, comprising the step of treating the subject with TYMP protein.
  • the present invention provides a method for improving hair loss comprising the step of treating the subject with a TYMP protein.
  • the present invention provides a method for promoting hair growth or hair growth comprising a; treating the subject with a TYMP protein.
  • composition for preventing hair loss or promoting hair growth comprising TYMP (thymidine phosphorylase) protein according to the present invention as an active ingredient has no side effects when treating hair loss, and can be used as a medicine due to its excellent hair growth effect even in a short time. It can be usefully used for health functional food.
  • TYMP thymidine phosphorylase
  • Figure 1 is a diagram showing the results of measuring the cell proliferation for 40 hours after treatment with TYMP protein DPC.
  • Figure 2 is a diagram showing the dorsal portion of the mouse after 15 days after subcutaneous injection of TYMP protein after removing hair using a hair removal agent in the back of C3H / HeN mice.
  • Figure 3 is a diagram showing the result of measuring the increased hair growth weight (mg) of the mouse after 15 days after subcutaneous injection of TYMP protein after hair removal using a hair removal agent in the back of C3H / HeN mice.
  • the present invention provides a pharmaceutical composition for preventing or treating hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • TYMP thymidine phosphorylase
  • TYMP is an enzyme that reversibly converts thymidine into thymine and 2-deoxyribose-1-phosphate and is known to be involved in DNA synthesis.
  • high expression of TYMP was observed in various solid tumors, centering on gastric cancer and colorectal cancer, and positive expression correlated with angiogenesis, invasion, metastasis, and expression of TYMP was one of the prognostic factors. was found to be.
  • high expression at the site of the disease has been reported, mainly in inflammatory diseases, in patients with glomerulonephritis, interstitial cystitis, chronic arthritis rheumatism, and inflammatory bowel disease.
  • TYMP is associated with hair loss symptoms and hair growth effects.
  • the TYMP protein may consist of all or part of a peptide having a prophylactic effect of preventing or treating hair loss, hair growth or hair growth, and may preferably be composed of the amino acid sequence of SEQ ID NO: 1, and functional equivalents and variants of the protein. It includes.
  • proteins and polypeptides that do not alter the activity of the protein molecule as a whole and proteins that can function functionally are included in the scope of the present invention.
  • the variant may be, for example, one or several amino acids deleted, substituted or added to the amino acid sequence, having 95% or more, preferably 98% or more, and more preferably 99% or more identity with the amino acid sequence.
  • identity means that the other amino acid sequence includes the gap between two amino acid sequences or the other amino acid sequences, including the number of gaps, when the gap is introduced to the highest amino acid sequence. The ratio (%) of the number of the same amino acid residue of the amino acid sequence of is referred to.
  • a few means the integer of 2-10, for example, the integer of 2-7, 2-5, 2-4, 2-3.
  • the variant based on polymorphisms such as SNP (monobasic polymorphism), a splice variant, etc. are mentioned.
  • the substitution is a conservative amino acid substitution. It is because conservative amino acid substitutions can have a structure or property substantially equivalent to human TYMP which has the said amino acid sequence.
  • amino acids are non-polar amino acids (glycine, alanine, phenylalanine, valine, leucine, isoleucine, methionine, proline, tryptophan) and polar amino acids (amino acids other than nonpolar amino acids), charged amino acids (acidic amino acids (aspartic acid, glutamic acid) and basic) Amino acids (arginine, histidine, lysine)) and uncharged amino acids (amino acids other than charged amino acids), aromatic amino acids (phenylalanine, tryptophan, tyrosine), branched amino acids (leucine, isoleucine, valine) and aliphatic amino acids (glycine, alanine, leucine) , Isoleucine, valine), and the like are known.
  • the protein may include a protein having increased structural stability or increased protein activity against heat, pH, etc. of the protein by variation or modification on the amino acid sequence.
  • the gene encoding the TYMP protein may be composed of the nucleotide sequence of SEQ ID NO: 2, variants which can function functionally the same as the nucleotides are included in the scope of the present invention.
  • the variant capable of the functionally identical function is at least 70%, preferably 80% or more, more preferably 90% or more of the nucleotide sequence represented by SEQ ID NO: 2 as a result of the addition, substitution or deletion of base. And, more preferably, having a sequence homology of 95% or more, it means a base sequence capable of encoding a protein that exhibits substantially homogeneous physiological activity with a protein encoded by the nucleotide sequence represented by SEQ ID NO: 2. For example, although some sequences have been modified by deletion, substitution or insertion, they include variants that can function functionally identical to nucleic acid molecules encoding the TYMP protein. It is a concept.
  • the term 'hair loss' may fall under the normal hair growth level if the number of hairs is less than the general number without any particular limitation, and preferably consists of male hair loss, female hair loss, circular hair loss and resting hair loss. Any one or more selected from the group may correspond to hair loss being treated or prevented by the composition according to the present invention.
  • the composition according to the present invention is also excellent in preventing hair loss before hair loss begins.
  • the term 'hair growth' refers to hairy, and 'hair growth' refers to hair growth.
  • the effect of the composition according to the invention also includes the effect of promoting hair growth or hair growth.
  • prevention means any action that inhibits or delays hair loss by administration of a composition of the present invention
  • treatment means that the symptoms caused by hair loss are improved or beneficially altered by the composition of the present invention. It means all actions.
  • compositions of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
  • pharmaceutical compositions according to the invention are each formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, and sterile injectable solutions according to a conventional method. Can be used. Suitable formulations known in the art are preferably those described in the literature.
  • Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • the pharmaceutical composition When formulating the pharmaceutical composition according to the present invention, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are commonly used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, and the like in the active ingredient. Mix is prepared.
  • lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral administration include suspensions, solution solutions, emulsions, and syrups, and various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, etc. may be used.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • composition of the present invention may be administered in a pharmaceutically effective amount.
  • the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level is determined by the type and severity, age, sex, disease of the individual. It can be determined according to the type, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including the drug used concurrently, and other factors well known in the medical field.
  • the compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations.
  • the preferred dosage of the composition of the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration of time, and the suitable total daily dosage can be determined by the practitioner within the correct medical judgment. 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, may be administered once to several times daily.
  • the object is not particularly limited as long as it is an object for the purpose of preventing or treating hair loss, and any object can be applied.
  • transdermal administration through topical application may be used, but is not limited thereto.
  • the method of administering the pharmaceutical composition according to the present invention is not particularly limited, and may be administered orally, or applied to the hair loss site or applied to the site where the progress of hair loss is foreseen.
  • the method of administration there is no particular limitation on the method of administration, and it is also possible to inject directly in the form of injection to the site where hair loss or progression of hair loss is foreseen.
  • the method of administration is not particularly limited, so it is possible to inject by injection into an artery or vein.
  • the dosage level selected from the composition will also depend on the activity of the active ingredient, the route of administration, the severity of the hair loss being treated and the condition and previous history of hair loss being treated. However, it is within the knowledge of the art to start with a lower dose of active ingredient than is required to achieve the desired therapeutic effect, and gradually increase the dosage until the desired effect is achieved. It can be determined according to gender, body type and weight.
  • the composition may be further processed before being formulated into a pharmaceutically acceptable pharmaceutical formulation, and may preferably be ground or ground into smaller particles. The composition will also vary depending on the condition and the patient being treated, but this can be determined non-originally.
  • compositions of the present invention have formulations that can be administered by methods such as direct application or spreading on the skin, such as hair or scalp, such as creams, lotions, ointments, aerosols, shampoos, gels, or packs. It may be.
  • Methods for the formulation or formulation suitable for each formulation are well known in the art. Those skilled in the art can appropriately select and use various combinations of ingredients used to prepare conventional external preparations in preparing these formulations.
  • Hair to which the composition of the present invention is applied includes hair follicles and hair follicles of the head, hair and eyelashes, and eyelashes, beards, armpits, pubic hair, and all parts of the hair root and hair follicles throughout the body.
  • the present invention also provides a quasi-drug composition for preventing or improving hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • the term "quasi drug” refers to a fiber, rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or animal, has a weak action on the human body or does not directly act on the human body, Or non-machinery and the like, or any of the agents used for sterilization, insecticide, and similar purposes for the prevention of infection, for the purpose of diagnosing, treating, reducing, treating or preventing human or animal diseases.
  • articles to be used which are not instruments, machines or devices, and articles which are used for the purpose of pharmacologically affecting the structure and function of humans or animals, except those which are not instruments, machines or devices. Also includes supplies.
  • the composition of the present invention When the composition of the present invention is included in a quasi-drug for the purpose of preventing or improving hair loss, promoting hair growth or hair growth, the composition may be used as it is or may be used together with other quasi-drug components, and may be appropriately used according to a conventional method. have.
  • the mixing amount of the active ingredient can be appropriately determined depending on the intended use.
  • the quasi-drug of the present invention is not particularly limited thereto, but may be prepared and used, for example, in the form of a cream, lotion, aerosol, shampoo, gel or pack.
  • creams, ointments, shampoos, gels or packs white petrolatum, yellow petrolatum, lanolin, bleached beeswax, cetanol, stearyl alcohol, stearic acid, hardened oil, gelled hydrocarbons, polyethylene glycol, liquid paraffin, squalane, etc.
  • Solvents and dissolving aids such as oleic acid, isopropyl myristate, glycerin triisooctanoate, crotamiton, diethyl sebacate, diisopropyl adipropyl, hexyl laurate, fatty acids, fatty acid esters, aliphatic alcohols and vegetable oils;
  • Antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene and butylhydroxyanisole; Preservatives such as parahydroxybenzoic acid ester;
  • Moisturizing agents such as glycerin, propylene glycol and sodium hyaluronate;
  • Surfactants such as polyoxyethylene derivative, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester and lecithin;
  • Thickeners such as carboxyvinyl
  • a stabilizer, a preservative, an absorption promoter, a pH adjuster, and other suitable additives can be mix
  • the present invention provides a cosmetic composition for preventing or improving hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • the cosmetic composition is a skin external preparation formulation of hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder gel, hair pack, hair treatment, eyebrow regrowth, eyelash regrowth, eyelash It may be a formulation of a nutrient, but is not limited thereto.
  • composition for preventing or improving hair loss, hair growth or hair growth promoting composition of the present invention can be used for pets different from the formulation.
  • it can be prepared in various forms such as solution, sol-gel, emulsion, oil, wax, aerosol, etc. such as pet shampoo and pet rinse. It can be prepared by addition.
  • the cosmetic composition of the present invention may include without limitation the conventionally acceptable ingredients in addition to the active ingredient, and includes conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers. can do.
  • conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers. can do.
  • any one or more of a synthetic surfactant, a preservative, a thickening agent, a viscosity adjusting agent, a pH adjusting agent, a perfume, a dye, a hair conditioner, and water, which are cleaning components, may be contained.
  • synthetic anionic surfactants include alkyl and alkyl ether sulfates, and representative examples thereof include sodium lauryl sulfate, lauryl ammonium sulfate, lauryl sulfate triethanolamine, polyoxyethylene lauryl sulfate, and polyoxyethylene lauryl ammonium sulfate. have.
  • synthetic amphoteric surfactants are alkyl betamin and alkyl amidopropyl betaine, and representative examples thereof are cocodimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, lauryl dimethyl alpha-carboxyethyl betaine. , Cetyl dimethyl carboxymethyl betaine, cocamidopropyl betaine and the like.
  • the nonionic surfactants include alkanol amides and amine oxides, such as lauryl diethyl amine oxide, palm oil alkyldimethyl amine oxide, lauric acid diethanol amide, palm oil fatty acid diethanolamide, palm oil fatty acid monoethanolamide, and the like.
  • optional ingredients used in the present invention are well known to those skilled in the art as conventional optional ingredients for maintaining basic physical properties and quality as shampoos.
  • Such optional ingredients include pearlescent aids, preservatives, thickeners and viscosity adjusting agents, pH adjusting agents, perfumes, dyes, hair conditioning agents.
  • Pearlescent aids such as, for example, ethylene glycol monostearate, ethylene glycol distearate; Preservatives such as methyl paraoxycyanate, methylchloro isothiazolinone and a mixture of methyl isothiazolinone; Thickeners and viscosity modifiers such as sodium chloride, ammonium chloride, propylene glycol; PH adjusters such as citric acid, phosphoric acid, sodium hydroxide, potassium hydroxide; Dyestuffs such as polyquaternium-10, polyquaternium-7, methylpolysiloxanes, dimethiconecopolyols, hair conditioning agents such as hydrolyzed animal proteins, water soluble tars are used, and fragrance may also be used.
  • Preservatives such as methyl paraoxycyanate, methylchloro isothiazolinone and a mixture of methyl isothiazolinone
  • Thickeners and viscosity modifiers such as sodium chloride, ammonium chloride,
  • the present invention also provides a food composition for preventing or improving hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  • the food composition of the present invention may be in the form of a dietary supplement
  • the "health supplement” refers to a food prepared and processed using raw materials or ingredients having useful functions to the human body according to Act No. 6767 of the Act on Dietary Supplement.
  • “Functional” means ingestion for the purpose of obtaining useful effects on health use such as nutrient control or physiological action on the structure and function of the human body.
  • the food composition may further include food additives, and the suitability as a "food additive", unless otherwise specified, according to the General Regulations of the Food Additives Code and General Test Methods, etc. Judging by the criteria.
  • Items listed in the "Food Additives Code” include, for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamon acid, natural additives such as navy, licorice extract, crystalline cellulose, guar gum, L- Mixed preparations, such as a glutamate sodium preparation, a noodles addition alkali preparation, a preservative preparation, and a tar pigment preparation, are mentioned.
  • chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamon acid, natural additives such as navy, licorice extract, crystalline cellulose, guar gum, L- Mixed preparations, such as a glutamate sodium preparation, a noodles addition alkali preparation, a preservative preparation, and a tar pigment preparation, are mentioned.
  • Foods containing the active ingredient of the present invention includes breads, rice cakes, dried fruits, candy, chocolates, chewing gum, confectionery such as ice cream, ice cream products such as ice cream, ice cream powder milk, low fat milk, lactose milk, Processed Milk, Goat Milk, Fermented Milk, Butter Oil, Concentrated Milk, Milk Cream, Butter Oil, Natural Cheese, Processed Cheese, Powdered Milk, Dairy Products such as Whey, Meat Products, Processed Products, Meat Products such as Hamburgers, Ham, Fish products such as sausages, bacon and other processed meat products Ramen noodles, dried noodles, raw noodles, noodle soups, delicacies, dried noodles, improved noodles, frozen noodles, pasta noodles, fruit drinks, vegetable drinks, carbonated drinks, soy milk products, Lactic acid bacteria beverages such as yogurt, beverages such as mixed drinks, soy sauce, miso, red pepper paste, chunjang, cheongukjang, mixed soy sauce, vinegar, sauces, seasoned foods such as tomato ketchup, curry
  • the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonating agents used in the carbonated beverage.
  • the composition of the present invention may include a pulp for the production of natural fruit juice, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical but is usually 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 including the active ingredient of the present invention is not particularly limited to other ingredients other than the above-mentioned protein, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates include monosaccharides (eg, glucose, fructose, and the like); Disaccharides (eg maltose, sucrose and the like); And conventional sugars such as polysaccharides (eg dextrin, cyclodextrin, etc.), and sugar alcohols such as xylitol, sorbitol, erythritol.
  • natural flavoring agents tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have.
  • the present invention also provides a method for preventing or treating hair loss, comprising the step of treating the subject with TYMP protein.
  • the present invention provides a method for improving hair loss comprising the step of treating the subject with a TYMP protein.
  • the present invention provides a method for promoting hair growth or hair growth comprising a; treating the subject with a TYMP protein.
  • TYMPine (thymidine phosphorylase) protein was purchased from Peprotech. The results of analyzing and confirming the amino acid sequence and the DNA base sequence of the obtained TYMP protein are shown in SEQ ID NOs: 1 and 2.
  • DPC Human dermal papilla cell proliferation experiments, a representative in vitro cell test system for measuring hair proliferation, were performed. 1 ng / ml or 5 ng / ml of the TYMP protein of Example 1 was treated with DPC, and the result of measuring proliferation for 40 hours is shown in FIG. 1.
  • the TYMP protein has an excellent cell proliferation effect and thus can be used for hair loss treatment or promotion of hair growth.
  • the measured hair growth weight was found to be 90 mg in the TYMP protein treated group, compared to 40 mg in the control group, and it was confirmed that the hair growth promoting effect was excellent when the TYMP protein was treated. .
  • the TYMP protein component has an excellent hair growth effect and can be used as a composition for preventing and treating hair loss.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • tablets are prepared by tableting according to a conventional method for preparing tablets.
  • the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
  • the amount of the above ingredient is prepared per ampoule (2 ml).
  • Carboxy vinyl polymer 1.5 wt%
  • Carboxy vinyl polymer 1.0 wt%
  • Vitamin B6 0.5 mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

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Abstract

The present invention relates to a composition comprising a TYMP protein as an effective ingredient for prevention, treatment, or alleviation of hair loss and for promotion of hair growth and hair development. A composition comprising a TYMP protein as an effective ingredient for prevention of hair loss and promotion of hair growth according to the present invention shows an outstanding hair growth effect within a short time without side effects upon use in the treatment of hair loss and thus can be effectively used as a drug as well as in quasi-drugs, cosmetics, and health functional foods.

Description

[규칙 제26조에 의한 보정 09.08.2017] TYMP(Thymidine Phosphorylase) 단백질을 유효성분으로 포함하는 탈모 예방 또는 치료용 약학적 조성물[Revision according to Rule 26.08.2017] A pharmaceutical composition for preventing or treating hair loss comprising TYMP (Thymidine Phosphorylase) protein as an active ingredient
본 발명은 TYMP(thymidine phosphorylase) 단백질을 유효성분으로 포함하는 탈모 예방 또는 치료용 약학적 조성물, 탈모 예방 또는 개선용 조성물, 발모 또는 육모 촉진용 조성물, 탈모 예방 또는 치료 방법, 탈모 개선 방법 및 발모 또는 육모 촉진 방법에 관한 것이다.The present invention is a pharmaceutical composition for preventing or treating hair loss, a composition for preventing or improving hair loss, a composition for preventing or improving hair loss, a composition for promoting hair growth or promoting hair loss, a method for preventing or treating hair loss, a method for improving hair loss, and a hair growth comprising a thymidine phosphorylase (TYMP) protein as an active ingredient It is about hair growth promotion method.
탈모는 정상적으로 모발이 존재하는 부위에 모발이 없는 상태를 말하며, 일반적으로 두피의 성모(굵고 검은 머리털)가 빠지는 것을 의미한다. 성모는 색깔이 없고 굵기가 가는 연모와는 달리 빠질 경우 미용상 문제를 일으킬 수 있다. 서양인에 비해 모발 밀도가 낮은 우리나라 사람의 경우 5-7 만개 정도의 머리카락이 있으며, 하루에 약 50-70 개까지의 머리카락이 빠지는 것은 정상적인 현상이다. 따라서 자고 나서나 머리를 감을 때 빠지는 머리카락의 수가 100 개가 넘으면 탈모가 진행 중일 가능성이 있다.Hair loss refers to a condition in which hair is not normally present in the area where hair is normally present, and generally means that the hair of the scalp (coarse black hair) falls out. Unlike virgin hair, which has no color and thick color, it can cause cosmetic problems if it falls out. Koreans with lower hair density than Westerners have 5-70,000 hairs, and about 50-70 hairs per day are normal. Therefore, hair loss may be in progress if the number of hairs that fall after sleeping or when you wash your hair exceeds 100.
이러한 탈모의 원인은 다양한데, 대머리의 발생에는 유전적 원인과 남성 호르몬인 안드로겐(androgen)이 중요한 인자로 생각되고 있으며, 여성형 탈모에서도 일부는 남성형 탈모와 같은 경로로 일어나는 것으로 추정되고 있으나 임상적으로 그 양상에 차이가 있다. 원형 탈모증은 자가 면역 질환으로 생각되고 있다. 휴지기 탈모증은 내분비 질환, 영양 결핍, 약물 사용, 출산, 발열, 수술 등의 심한 신체적, 정신적 스트레스 후 발생하는 일시적인 탈모로 모발의 일부가 생장 기간을 다 채우지 못하고 휴지기 상태로 이행하여 탈락됨으로써 발생한다.There are many causes of hair loss, and genetic causes and androgens (androgens) are considered to be important factors for baldness, and some of the female hair loss is believed to occur in the same path as male hair loss. There is a difference in aspects. Alopecia areata is thought to be an autoimmune disease. Resting alopecia is a temporary hair loss that occurs after severe physical and mental stress such as endocrine disease, nutritional deficiency, drug use, childbirth, fever, and surgery.
또한, 이러한 탈모의 증상 중, 남성형 탈모는 대머리의 가족력이 있는 사람에서 20 대나 30 대부터 모발이 점차 가늘어지며 탈모가 진행된다. 이마와 머리털의 경계선이 뒤로 밀리면서 양측 측두부로 M자 모양으로 이마가 넓어지며 머리 정수리 부위에도 탈모가 서서히 진행된다. 여성형 탈모는 남성형 탈모와 비교하여 이마 위의 모발선이 유지되면서 머리 중심부의 모발이 가늘어지고 머리숱이 적어지는 특징을 가진다. 또한 여성형 탈모는 탈모의 정도가 약하여 남성형 탈모에서처럼 이마가 벗겨지고 완전한 대머리가 되는 경우는 드물다. 또한 원형 탈모증은 다양한 크기의 원형 또는 타원형의 탈모반(모발이 소실되어 점처럼 보이는 것)이 발생하는 점이 특징적이다. 주로 머리에 발생하며, 드물게 수염, 눈썹이나 속눈썹에도 생길 수 있으며 증상 부위가 확대되면서 큰 탈모반이 형성되기도 한다. 머리카락 전체가 빠지면 온머리 탈모증(전두 탈모증), 전신의 털이 빠지면 전신 탈모증이라 구분한다. 또한 휴지기 탈모증은 원인 자극 발생 후 2~4 개월 후부터 탈모가 시작되어 전체적으로 머리 숱이 감소하게 되며 원인 자극이 제거되면 수개월에 걸쳐 휴지기 모발이 정상으로 회복됨에 따라 모발 탈락은 감소하게 된다.In addition, among the symptoms of the hair loss, male-type hair loss is gradually thinning hair from the 20s or 30s in people with a family history of baldness, hair loss proceeds. As the forehead and head line is pushed backward, the forehead widens in the M-shape with both temporal heads and hair loss progresses gradually in the crown of the head. Female hair loss is characterized in that the hairline on the forehead is thinned and hair thinner compared to male hair loss. In addition, female hair loss is so weak that hair loss is rare and complete baldness, as in male hair loss. Alopecia areata is also characterized by the development of round or oval bald spots of varying sizes (hair loss that looks like dots). It usually occurs on the head, and rarely can occur on the beard, eyebrows or eyelashes, and the enlarged area of symptoms may cause large bald area to form. If the entire hair falls out, alopecia areata (frontal alopecia), if the hair falls out of the systemic hair loss. In addition, alopecia areata starts hair loss from 2 to 4 months after causative stimulus occurs, and hair thinning is reduced overall. As the causative stimulus is removed, hair loss is reduced as restorative hair returns to normal for several months.
한편 이러한 탈모에 대한 종래 치료방법으로는 남성형 또는 여성형 탈모의 경우에는 미녹시딜 등의 바르는 약, 피나스테라이드 등의 먹는 약, 모발 이식술 등이 이용되고 있다. 또한 원형 탈모증의 치료를 위해서는 국소 스테로이드 제제나 전신 스테로이드 제제, 면역 요법 등이 이용되고 있다. 휴지기 탈모증은 원인이 제거되면 모발이 회복되므로 원인을 확인하고 치료하는 것이 중요하다. 하지만, 이러한 종래 방법에 의해 탈모를 치료하는 경우 약물 요법이나 스테로이드 제제 등에 의존하기 때문에 부작용의 문제가 있고, 치료의 속도도 빠르지 않아 장기간이라는 문제점이 있었다. 또한 약물 또는 모발 이식 등을 이용하여 치료하게 되면 치료 비용도 크게 상승한다는 문제점이 있다. 미녹시딜과 피나스테라이드는 모발성장촉진을 위해 쓰이고 있는 대표적인 약물들이다. 미국 업존사의 미녹시딜(minoxidil)은 장기 적용 시 부종, 부정맥과 원하지 않는 부위에 털이 나는 등의 부작용을 초래할 수 있으며, 미녹시딜의 효과는 사용으로부터 6개월에서 1년 사이에 가장 큰 효과를 보이고 이후에는 서서히 그 효과가 줄어드는 것으로 알려져 있다. 또한 머크사에서 개발한 피나스테라이드(finasteride)는 모낭에서 남성호르몬 테스토스테론 대사에 작용하는 효소인 5-α-리덕테이즈(5-α-reductase)의 활성을 억제하는 물질로 알려져 있으나 성기능 장애와 우울증 및 자살충동의 증가가 보고된 바 있다. 또한 기형아 출산의 가능성을 높이기 때문에 가임기의 여성이나 임신 중의 여성에게는 적용이 불가능하다. 게다가, 두 약물 모두 적용을 중단할 경우 다시 탈모가 진행되는 것으로 알려져 있다. 이 외에도 발프로산이 있지만, 임신 중 복용할 경우 아이의 인지발달 능력이 크게 떨어진다고 알려져 있다. 이처럼 종래의 여러 종류의 발모제는 일반적으로 두피의 혈행 촉진과 모근의 영양공급을 목적으로 하여 모발의 성장에 도움을 주도록 하는 방법이 시도되었으나 이 역시 독성과 부작용이 심하고 그 효과 또한 미흡한 것이 현재 실정이다.On the other hand, as a conventional treatment for hair loss, a male or female hair loss drug such as minoxidil, a drug such as finasteride, a hair transplant, and the like are used. For the treatment of alopecia areata, topical steroid preparations, systemic steroid preparations, immunotherapy and the like are used. Resting alopecia causes hair to recover when the cause is removed, so it is important to identify and treat the cause. However, when treating hair loss by such a conventional method, there is a problem of side effects because it depends on drug therapy, steroid preparations, etc. In addition, there is a problem that the treatment cost also increases significantly if the treatment using drugs or hair transplantation. Minoxidil and finasteride are representative drugs used to promote hair growth. Minoxidil from the US Upzone may cause side effects such as swelling, arrhythmia and unwanted hairs on long term application.The effect of minoxidil is most effective between 6 months and 1 year from use and then gradually It is known that the effect is reduced. Finasteride, developed by Merck, is known to inhibit the activity of 5-α-reductase, an enzyme that acts on male hormone testosterone metabolism in hair follicles. An increase in suicidal thoughts has been reported. In addition, it is not applicable to women of childbearing age or pregnant women because it increases the probability of birth of birth defects. Moreover, it is known that hair loss progresses again if both drugs are discontinued. There is also Valproic acid, but taking it during pregnancy is known to greatly reduce the child's cognitive development ability. As mentioned above, various types of conventional hair regrowth have been attempted to help hair growth for the purpose of promoting blood circulation of the scalp and nourishing hair roots. However, the present invention is also toxic and side effects are severe and the effect is insufficient. .
이에 본 발명자들은, 부작용 없이 탈모를 방지하고 발모를 촉진할 수 있는 물질을 개발하고자 예의 노력한 결과, 체내에 존재하는 TYMP(thymidine phosphorylase) 단백질이 모발성장을 촉진하는 효과가 있음을 확인하고 본 발명을 완성하였다.Accordingly, the present inventors have made intensive efforts to develop a material capable of preventing hair loss and promoting hair growth without side effects, and confirmed that the TYMP (thymidine phosphorylase) protein present in the body has an effect of promoting hair growth. Completed.
본 발명의 목적은 TYMP(thymidine phosphorylase) 단백질을 유효성분으로 포함하는 탈모 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating hair loss comprising TYMP (thymidine phosphorylase) protein as an active ingredient.
본 발명의 다른 목적은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 의약외품 조성물, 화장료 조성물 및 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a quasi-drug composition, cosmetic composition and food composition for preventing or improving hair loss containing TYMP protein as an active ingredient.
본 발명의 또 다른 목적은 TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 약학적 조성물, 의약외품 조성물, 화장료 조성물 및 식품 조성물을 제공하는 것이다.Another object of the present invention to provide a pharmaceutical composition, quasi-drug composition, cosmetic composition and food composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
본 발명의 또 다른 목적은 TYMP 단백질을 개체에 처리하는 단계;를 포함하는 탈모 예방 또는 치료 방법, 탈모 개선 방법 및 발모 또는 육모 촉진 방법을 제공하는 것이다.Still another object of the present invention is to provide a method for preventing or treating hair loss, a method for improving hair loss, and a method for promoting hair growth or hair growth, comprising: treating a subject with TYMP protein.
상기 목적을 달성하기 위하여, 본 발명은 TYMP(thymidine phosphorylase) 단백질을 유효성분으로 포함하는 탈모 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of hair loss comprising TYMP (thymidine phosphorylase) protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
또한, 본 발명은 TYMP 단백질을 개체에 처리하는 단계;를 포함하는 탈모 예방 또는 치료 방법을 제공한다.The present invention also provides a method for preventing or treating hair loss, comprising the step of treating the subject with TYMP protein.
또한, 본 발명은 TYMP 단백질을 개체에 처리하는 단계;를 포함하는 탈모 개선 방법을 제공한다.In addition, the present invention provides a method for improving hair loss comprising the step of treating the subject with a TYMP protein.
또한, 본 발명은 TYMP 단백질을 개체에 처리하는 단계;를 포함하는 발모 또는 육모 촉진 방법을 제공한다.In addition, the present invention provides a method for promoting hair growth or hair growth comprising a; treating the subject with a TYMP protein.
본 발명에 따른 TYMP(thymidine phosphorylase) 단백질을 유효성분으로 포함하는 탈모 예방 또는 발모 촉진용 조성물은 탈모 치료시 부작용이 없고, 단시간에도 발모 효과가 우수하여 의약품으로 이용가능 할 뿐만 아니라, 의약외품, 화장품 및 건강기능식품에도 유용하게 이용될 수 있다.The composition for preventing hair loss or promoting hair growth comprising TYMP (thymidine phosphorylase) protein according to the present invention as an active ingredient has no side effects when treating hair loss, and can be used as a medicine due to its excellent hair growth effect even in a short time. It can be usefully used for health functional food.
도 1은 TYMP 단백질을 DPC에 처리하고 40시간 동안의 세포증식을 측정한 결과를 나타낸 도이다.Figure 1 is a diagram showing the results of measuring the cell proliferation for 40 hours after treatment with TYMP protein DPC.
도 2는 C3H/HeN 마우스의 등을 제모제를 이용하여 털을 제거한 후 TYMP 단백질을 피하주사하고 15일이 경과한 뒤의 마우스의 등 부분 사진을 나타낸 도이다.Figure 2 is a diagram showing the dorsal portion of the mouse after 15 days after subcutaneous injection of TYMP protein after removing hair using a hair removal agent in the back of C3H / HeN mice.
도 3은 C3H/HeN 마우스의 등을 제모제를 이용하여 털을 제거한 후 TYMP 단백질을 피하주사하고 15일이 경과한 후 마우스의 증가한 발모 무게(mg)를 측정한 결과를 나타낸 도이다.Figure 3 is a diagram showing the result of measuring the increased hair growth weight (mg) of the mouse after 15 days after subcutaneous injection of TYMP protein after hair removal using a hair removal agent in the back of C3H / HeN mice.
이하, 본 발명에 대해 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 치료용 및 발모 또는 육모 촉진용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
TYMP(thymidine phosphorylase)은 티미딘을 티민과 2-데옥시리보오스-1-인산으로 가역적으로 변환하는 효소이며, DNA 합성에 관여하고 있는 것으로 알려져 있다. 또, 위암, 대장암을 중심으로 하여, 다양한 고형 종양에 있어서 TYMP 의 고발현이 확인되어, 혈관 신생, 침윤, 전이 등과 발현량이 정 (正) 의 상관 관계가 있고, TYMP 의 발현이 예후 인자의 하나인 것으로 밝혀졌다. 그 밖의 병태의 관련에 대해서도, 염증 질환을 중심으로, 사구체신염, 간질성 방광염, 만성 관절 류머티즘, 염증성 장질환 환자에 있어서 병태 부위에서의 고발현이 보고되어 있다. 그러나, TYMP가 탈모증상 및 발모효과와 관련이 있다는 것에 대해서는 아직 보고된 바가 없다.TYMP (thymidine phosphorylase) is an enzyme that reversibly converts thymidine into thymine and 2-deoxyribose-1-phosphate and is known to be involved in DNA synthesis. In addition, high expression of TYMP was observed in various solid tumors, centering on gastric cancer and colorectal cancer, and positive expression correlated with angiogenesis, invasion, metastasis, and expression of TYMP was one of the prognostic factors. Was found to be. In relation to other conditions, high expression at the site of the disease has been reported, mainly in inflammatory diseases, in patients with glomerulonephritis, interstitial cystitis, chronic arthritis rheumatism, and inflammatory bowel disease. However, it has not been reported that TYMP is associated with hair loss symptoms and hair growth effects.
TYMP 단백질은 탈모의 예방 또는 치료, 발모 또는 육모의 촉진 효과를 갖는 전체 또는 일부 펩타이드로 구성될 수 있으며, 바람직하게는 서열번호 1의 아미노산 서열로 구성될 수 있고, 상기 단백질의 기능적 동등물 및 변이체를 포함한다.The TYMP protein may consist of all or part of a peptide having a prophylactic effect of preventing or treating hair loss, hair growth or hair growth, and may preferably be composed of the amino acid sequence of SEQ ID NO: 1, and functional equivalents and variants of the protein. It includes.
상기 단백질의 기능적 동등물이란, 단백질 분자의 활성을 전체적으로 변경시키지 않는 단백질 및 폴리펩티드를 포함하는 것으로 기능적으로 동일한 작용을 할 수 있는 단백질이 본 발명의 범위에 포함된다. 상기 변이체란, 예를 들면 상기 아미노산 서열에서 하나 또는 수개의 아미노산이 결실, 치환 또는 부가된 것, 상기 아미노산 서열과 95 % 이상, 바람직하게는 98 % 이상, 보다 바람직하게는 99 % 이상의 동일성을 갖는 것 등을 말한다. 여기서 "동일성"이란, 2개의 아미노산 서열에 갭을 도입하거나, 도입하지 않고 가장 높은 일치도가 되도록 정렬(얼라인먼트)시켰을 때에, 상기 갭의 수를 포함한, 한쪽 아미노산 서열의 전체 아미노산 잔기수에 대한 다른 쪽의 아미노산 서열의 동일한 아미노산 잔기수의 비율(%)을 말한다. 또한, "수개"란, 2 내지 10의 정수, 예를 들면 2 내지 7, 2 내지 5, 2 내지 4, 2 내지 3의 정수를 말한다. 천연 변이체의 구체예로는 SNP(일염기 다형) 등의 다형에 기초하는 변이체나 스플라이스 변이체 등을 들 수 있다. 상기 치환은 보존적 아미노산 치환인 것이 바람직하다. 보존적 아미노산 치환이면, 상기 아미노산 서열을 갖는 인간 TYMP와 실질적으로 동등한 구조 또는 성질을 가질 수 있기 때문이다. 보존적 아미노산이란, 서로 비극성 아미노산(글리신, 알라닌, 페닐알라닌, 발린, 류신, 이소류신, 메티오닌, 프롤린, 트립토판) 및 극성 아미노산(비극성 아미노산 이외의 아미노산), 하전 아미노산(산성 아미노산(아스파라긴산, 글루탐산) 및 염기성 아미노산(아르기닌, 히스티딘, 리신)) 및 비하전 아미노산(하전 아미노산 이외의 아미노산), 방향족 아미노산(페닐알라닌, 트립토판, 티로신), 분지상 아미노산(류신, 이소류신, 발린) 및 지방족 아미노산(글리신, 알라닌, 류신, 이소류신, 발린) 등이 알려져 있다. 또한, 아미노산 서열상의 변이 또는 수식에 의해서 단백질의 열, pH등에 대한 구조적 안정성이 증가하거나 단백질 활성이 증가한 단백질을 포함할 수 있다.Functional equivalents of the proteins include proteins and polypeptides that do not alter the activity of the protein molecule as a whole, and proteins that can function functionally are included in the scope of the present invention. The variant may be, for example, one or several amino acids deleted, substituted or added to the amino acid sequence, having 95% or more, preferably 98% or more, and more preferably 99% or more identity with the amino acid sequence. Say things. Here, "identity" means that the other amino acid sequence includes the gap between two amino acid sequences or the other amino acid sequences, including the number of gaps, when the gap is introduced to the highest amino acid sequence. The ratio (%) of the number of the same amino acid residue of the amino acid sequence of is referred to. In addition, "a few" means the integer of 2-10, for example, the integer of 2-7, 2-5, 2-4, 2-3. As a specific example of a natural variant, the variant based on polymorphisms, such as SNP (monobasic polymorphism), a splice variant, etc. are mentioned. Preferably, the substitution is a conservative amino acid substitution. It is because conservative amino acid substitutions can have a structure or property substantially equivalent to human TYMP which has the said amino acid sequence. Conservative amino acids are non-polar amino acids (glycine, alanine, phenylalanine, valine, leucine, isoleucine, methionine, proline, tryptophan) and polar amino acids (amino acids other than nonpolar amino acids), charged amino acids (acidic amino acids (aspartic acid, glutamic acid) and basic) Amino acids (arginine, histidine, lysine)) and uncharged amino acids (amino acids other than charged amino acids), aromatic amino acids (phenylalanine, tryptophan, tyrosine), branched amino acids (leucine, isoleucine, valine) and aliphatic amino acids (glycine, alanine, leucine) , Isoleucine, valine), and the like are known. In addition, the protein may include a protein having increased structural stability or increased protein activity against heat, pH, etc. of the protein by variation or modification on the amino acid sequence.
TYMP 단백질을 코딩하는 유전자는 서열번호 2의 염기서열로 구성될 수 있으며, 상기 뉴클레오티드와 기능적으로 동일한 기능을 할 수 있는 변이체가 본 발명의 범위에 포함된다.The gene encoding the TYMP protein may be composed of the nucleotide sequence of SEQ ID NO: 2, variants which can function functionally the same as the nucleotides are included in the scope of the present invention.
상기 기능적으로 동일한 기능을 할 수 있는 변이체란, 염기의 부가, 치환 또는 결실의 결과, 서열번호 2로 표시되는 염기서열과 적어도 70% 이상, 바람직하게는 80% 이상, 더욱 바람직하게는 90% 이상, 더 더욱 바람직하게는 95% 이상의 서열 상동성을 갖는 것으로, 서열번호 2로 표시되는 염기서열에 의해 코딩된 단백질과 실질적으로 동질의 생리활성을 나타내는 단백질을 코딩할 수 있는 염기서열을 의미한다. 예를 들어, 일부 염기서열이 결실(deletion), 치환(substitution) 또는 삽입(insertion)에 의해 변형되었지만, 상기 TYMP 단백질을 코딩하는 핵산 분자와 기능적으로 동일한 작용을 할 수 있는 변이체(variants)를 포함하는 개념이다.The variant capable of the functionally identical function is at least 70%, preferably 80% or more, more preferably 90% or more of the nucleotide sequence represented by SEQ ID NO: 2 as a result of the addition, substitution or deletion of base. And, more preferably, having a sequence homology of 95% or more, it means a base sequence capable of encoding a protein that exhibits substantially homogeneous physiological activity with a protein encoded by the nucleotide sequence represented by SEQ ID NO: 2. For example, although some sequences have been modified by deletion, substitution or insertion, they include variants that can function functionally identical to nucleic acid molecules encoding the TYMP protein. It is a concept.
본 명세서에 사용된, 용어 '탈모'란 정상적인 발모 수준을 벗어나 머리카락의 숫자가 일반적인 숫자보다 적은 경우라면 특별한 제한 없이 이에 속할 수 있으며, 바람직하게는 남성형 탈모, 여성형 탈모, 원형 탈모 및 휴지기 탈모로 이루어지는 군으로부터 선택되는 어느 하나 이상의 것이 본 발명에 따른 조성물에 의해 치료 또는 예방되는 탈모에 해당할 수 있다. 또한 본 발명에 따른 조성물은 탈모가 시작되기 전에 탈모를 예방하는 효과도 우수하다.As used herein, the term 'hair loss' may fall under the normal hair growth level if the number of hairs is less than the general number without any particular limitation, and preferably consists of male hair loss, female hair loss, circular hair loss and resting hair loss. Any one or more selected from the group may correspond to hair loss being treated or prevented by the composition according to the present invention. In addition, the composition according to the present invention is also excellent in preventing hair loss before hair loss begins.
본 명세서에 사용된, 용어 '발모'란 털이 나는 것을 말하며, '육모'란 털이 자라나게 하는 것을 말한다. 본 발명에 따른 조성물의 효과에는 발모 또는 육모 촉진의 효과도 포함된다.As used herein, the term 'hair growth' refers to hairy, and 'hair growth' refers to hair growth. The effect of the composition according to the invention also includes the effect of promoting hair growth or hair growth.
본 명세서에 사용된, 용어 "예방"은 본 발명의 조성물의 투여로 탈모를 억제 또는 지연시키는 모든 행위를 의미하며, "치료"는 본 발명의 조성물에 의해 탈모에 의한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "prevention" means any action that inhibits or delays hair loss by administration of a composition of the present invention, and "treatment" means that the symptoms caused by hair loss are improved or beneficially altered by the composition of the present invention. It means all actions.
본 발명의 약학적 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 또한, 본 발명에 따른 약학적 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 당해 기술 분야에 알려진 적합한 제제는 문헌에 개시되어 있는 것을 사용하는 것이 바람직하다. The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions. In addition, the pharmaceutical compositions according to the invention are each formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, and sterile injectable solutions according to a conventional method. Can be used. Suitable formulations known in the art are preferably those described in the literature.
본 발명의 약학적 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
본 발명에 따른 약학적 조성물을 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 유효성분에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트, 수크로오스, 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 상기 비수성용제, 현탁제로는 프로필렌글라이콜(propylene glycol), 폴리에틸렌 글라이콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. When formulating the pharmaceutical composition according to the present invention, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, and the like in the active ingredient. Mix is prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solution solutions, emulsions, and syrups, and various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, etc. may be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 조성물은 약학적으로 유효한 양으로 투여할 수 있다. The composition of the present invention may be administered in a pharmaceutically effective amount.
본 발명에서 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 질병의 종류, 약물의 활성, 약물에 대한민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다. 본 발명의 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물 형태, 투여경로 및 기간에 따라 다르며, 적합한 총 1일 사용량은 올바른 의학적 판단범위 내에서 처치의에 의해 결정될 수 있으나, 일반적으로 0.001 내지 1000 mg/kg의 양, 바람직하게는 0.05 내지 200 mg/kg, 보다 바람직하게는 0.1 내지 100 mg/kg의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다. 상기 탈모의 예방 또는 치료를 목적으로 하는 개체이면 특별히 한정되지 않고, 어떠한 개체이든 적용 가능하다. 예를 들면, 원숭이, 개, 고양이, 토끼, 모르모트, 랫트, 마우스, 소, 양, 돼지, 염소 등과 같은 비인간동물 및 인간 등 어느 개체에나 적용할 수 있으며, 투여의 방식은 당업계의 통상적인 방법이라면 제한 없이 포함한다. 예를 들어, 국소도포 등을 통한 경피투여 방식을 사용할 수 있으나, 이에 제한되는 것은 아니다.As used herein, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level is determined by the type and severity, age, sex, disease of the individual. It can be determined according to the type, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including the drug used concurrently, and other factors well known in the medical field. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art. The preferred dosage of the composition of the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration of time, and the suitable total daily dosage can be determined by the practitioner within the correct medical judgment. 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, may be administered once to several times daily. The object is not particularly limited as long as it is an object for the purpose of preventing or treating hair loss, and any object can be applied. For example, it can be applied to any individual, such as monkeys, dogs, cats, rabbits, marmots, rats, mice, cows, sheep, pigs, goats, and the like, and to humans, and the mode of administration is conventional in the art. If not included. For example, transdermal administration through topical application may be used, but is not limited thereto.
한편, 본 발명에 따른 약학적 조성물의 투여 방법은 특별한 제한이 있는 것은 아니며, 경구 투여하거나 탈모 부위에 바르거나 탈모의 진행이 예견되는 부위에 바르는 형태로 투여할 수 있다. 또한 투여 방법에 특별한 제한이 있는 것은 아니기에 탈모 또는 탈모의 진행이 예견되는 부위에 주사의 형태로 직접 주입하는 것도 가능하다. 또한 투여 방법에 특별한 제한이 있는 것은 아니기에 동맥 또는 정맥 등에 주사하여 주입하는 것도 가능하다.On the other hand, the method of administering the pharmaceutical composition according to the present invention is not particularly limited, and may be administered orally, or applied to the hair loss site or applied to the site where the progress of hair loss is foreseen. In addition, there is no particular limitation on the method of administration, and it is also possible to inject directly in the form of injection to the site where hair loss or progression of hair loss is foreseen. In addition, the method of administration is not particularly limited, so it is possible to inject by injection into an artery or vein.
또한 상기 조성물로부터 선택되는 투여 수준은 유효성분의 활성, 투여 경로, 치료되는 탈모의 중증도 및 치료되는 탈모의 병태 및 이전 병력에 따를 것이다. 그러나 원하는 치료 효과의 달성을 위해 요구되는 것보다 낮은 수준의 유효성분의 용량에서 시작하여, 원하는 효과가 달성될 때까지 투여량을 서서히 증가시키는 것은 당업계의 지식 내에 있으며, 바람직한 투여량은 나이, 성별, 체형, 체중에 따라 결정될 수 있다. 상기 조성물은 약제학상 허용 가능한 제약 제제로 제제화 되기 전에 추가로 가공될 수 있으며, 바람직하게는 더 작은 입자들로 분쇄 또는 연마될 수 있다. 또한 상기 조성물은 병태 및 치료되는 환자에 따라 달라질 것이지만, 이는 비-독창적으로 결정할 수 있다.The dosage level selected from the composition will also depend on the activity of the active ingredient, the route of administration, the severity of the hair loss being treated and the condition and previous history of hair loss being treated. However, it is within the knowledge of the art to start with a lower dose of active ingredient than is required to achieve the desired therapeutic effect, and gradually increase the dosage until the desired effect is achieved. It can be determined according to gender, body type and weight. The composition may be further processed before being formulated into a pharmaceutically acceptable pharmaceutical formulation, and may preferably be ground or ground into smaller particles. The composition will also vary depending on the condition and the patient being treated, but this can be determined non-originally.
본 발명의 조성물은 피부, 예컨대 모발 또는 두피에 직접 도포 또는 산포하는 등의 방법에 의해 투여할 수 있는 제형, 예를 들어, 크림, 로션, 연고, 에어로졸, 샴푸, 겔, 또는 팩의 제형을 갖는 것일 수 있다. 각각의 제형에 적합한 배합성분이나 제제를 위한 방법은 당업계에 잘 알려져 있다. 당업자들은 이들 제제를 제조할 때, 통상의 외용제를 제조하는 데에 사용되는 각종 배합 성분을 적절히 선택하여 사용할 수 있다.The compositions of the present invention have formulations that can be administered by methods such as direct application or spreading on the skin, such as hair or scalp, such as creams, lotions, ointments, aerosols, shampoos, gels, or packs. It may be. Methods for the formulation or formulation suitable for each formulation are well known in the art. Those skilled in the art can appropriately select and use various combinations of ingredients used to prepare conventional external preparations in preparing these formulations.
본 발명의 조성물이 적용되는 모발이란, 머리의 모근 및 모낭, 머리카락 및 속눈썹과 겉눈썹, 수염, 겨드랑이, 음모, 신체 전반에 모근 및 모낭이 있는 모든 부위를 포함한다.Hair to which the composition of the present invention is applied includes hair follicles and hair follicles of the head, hair and eyelashes, and eyelashes, beards, armpits, pubic hair, and all parts of the hair root and hair follicles throughout the body.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 및 발모 또는 육모 촉진용 의약외품 조성물을 제공한다.The present invention also provides a quasi-drug composition for preventing or improving hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
본 발명에서 용어, "의약외품"은 사람이나 동물의 질병을 치료, 경감, 처치또는 예방할 목적으로 사용되는 섬유, 고무제품 또는 이와 유사한 것, 인체에 대한 작용이 약하거나 인체에 직접 작용하지 않으며, 기구 또는 기계가 아닌 것과 이와 유사한 것, 감염 예방을 위하여 살균, 살충 및 이와 유사한 용도로 사용되는 제제 중 하나에 해당하는 물품으로서, 사람이나 동물의 질병을 진단, 치료, 경감, 처치 또는 예방할 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것 및 사람이나 동물의 구조와 기능에 약리학적 영향을 줄 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것을 제외한 물품을 의미하며, 피부 외용제 및 개인위생용품도 포함한다.As used herein, the term "quasi drug" refers to a fiber, rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or animal, has a weak action on the human body or does not directly act on the human body, Or non-machinery and the like, or any of the agents used for sterilization, insecticide, and similar purposes for the prevention of infection, for the purpose of diagnosing, treating, reducing, treating or preventing human or animal diseases. Among articles to be used, which are not instruments, machines or devices, and articles which are used for the purpose of pharmacologically affecting the structure and function of humans or animals, except those which are not instruments, machines or devices. Also includes supplies.
본 발명의 조성물을 탈모의 예방 또는 개선, 발모 또는 육모 촉진을 목적으로 의약외품에 포함시킬 경우, 상기 조성물을 그대로 포함하여 사용하거나 다른 의약외품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효성분의 혼합량은 사용 목적에 따라 적합하게 결정할 수 있다.When the composition of the present invention is included in a quasi-drug for the purpose of preventing or improving hair loss, promoting hair growth or hair growth, the composition may be used as it is or may be used together with other quasi-drug components, and may be appropriately used according to a conventional method. have. The mixing amount of the active ingredient can be appropriately determined depending on the intended use.
본 발명의 의약외품은 특별히 이에 제한되지 않으나, 예를 들어 크림제, 로션제, 에어로졸제, 샴푸제, 젤제 또는 팩제의 형태로 제조되어 사용될 수 있다.The quasi-drug of the present invention is not particularly limited thereto, but may be prepared and used, for example, in the form of a cream, lotion, aerosol, shampoo, gel or pack.
크림제ㆍ연고제ㆍ샴푸제ㆍ젤제 또는 팩제의 경우에 있어서는, 백색 바셀린, 황색 바셀린, 라놀린, 표백 밀랍, 세탄올, 스테아릴알코올, 스테아르산, 경화유, 겔화 탄화수소, 폴리에틸렌글리콜, 유동 파라핀, 스쿠알란 등의 기제; 올레산, 미리스트산이소프로필, 트리이소옥탄산글리세린, 크로타미톤, 세바크산디에틸, 아디프산디이소프로필, 라우르산헥실, 지방산, 지방산 에스테르, 지방족 알코올, 식물유 등의 용제 및 용해 보조제; 토코페롤 유도체, L-아스코르브산, 디부틸하이드록시톨루엔, 부틸하이드록시아니솔 등의 산화 방지제; 파라하이드록시벤조산에스테르 등의 방부제; 글리세린, 프로필렌글리콜, 히알루론산나트륨 등의 보습제; 폴리옥시에틸렌유도체, 글리세린 지방산 에스테르, 자당 지방산 에스테르, 소르비탄 지방산 에스테르, 프로필렌글리콜 지방산 에스테르, 레시틴 등의 계면 활성제; 카르복시비닐 폴리머, 잔탄검, 카르복시메틸셀룰로오스, 카르복시메틸셀룰로오스나트륨염류, 하이드록시프로필셀룰로오스, 하이드록시프로필메틸셀룰로오스 등의 증점제 등이 있다.In the case of creams, ointments, shampoos, gels or packs, white petrolatum, yellow petrolatum, lanolin, bleached beeswax, cetanol, stearyl alcohol, stearic acid, hardened oil, gelled hydrocarbons, polyethylene glycol, liquid paraffin, squalane, etc. Mechanism of; Solvents and dissolving aids such as oleic acid, isopropyl myristate, glycerin triisooctanoate, crotamiton, diethyl sebacate, diisopropyl adipropyl, hexyl laurate, fatty acids, fatty acid esters, aliphatic alcohols and vegetable oils; Antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene and butylhydroxyanisole; Preservatives such as parahydroxybenzoic acid ester; Moisturizing agents such as glycerin, propylene glycol and sodium hyaluronate; Surfactants such as polyoxyethylene derivative, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester and lecithin; Thickeners such as carboxyvinyl polymer, xanthan gum, carboxymethyl cellulose, carboxymethyl cellulose sodium salts, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and the like.
에어로졸제의 경우에 있어서는, 연고제, 크림제, 겔제, 현탁제, 유제, 액제 및 로션제 등의 조제에 사용되는 백색 바셀린, 황색 바셀린, 라놀린, 표백 밀랍, 세탄올, 스테아릴알코올, 스테아르산, 경화유, 겔화 탄화수소, 폴리에틸렌글리콜, 유동 파라핀, 스쿠알란 등의 기제; 올레산, 미리스트산이소프로필, 아디프산디이소프로필, 세바크산이소프로필, 트리이소옥탄산글리세린, 크로타미톤, 세바크산디에틸, 라우르산헥실, 지방산, 지방산 에스테르, 지방족 알코올, 식물유 등의 용제 및 용해 보조제; 토코페롤 유도체, L-아스코르브산, 디부틸하이드록시톨루엔, 부틸하이드록시아니솔 등의 산화 방지제; 파라하이드록시벤조산에스테르 등의 방부제; 글리세린, 프로필렌글리콜, 히알루론산나트륨 등의 보습제; 폴리옥시에틸렌 유도체, 글리세린 지방산 에스테르, 자당 지방산에스테르, 소르비탄 지방산 에스테르, 프로필렌글리콜 지방산 에스테르, 레시틴 등의 계면 활성제; 카르복시비닐 폴리머, 잔탄검, 카르복시메틸셀룰로오스, 카르복시메틸셀룰로오스 나트륨염류, 하이드록시프로필셀룰로오스, 하이드록시프로필메틸셀룰로오스 등의 증점제; 추가로 각종 안정제, 완충제, 교미제, 현탁화제, 유화제, 방향제, 보존제, 용해 보조제, 그 밖의 적당한 첨가제를 배합할 수 있다.In the case of aerosols, white petrolatum, yellow petrolatum, lanolin, bleached beeswax, cetanol, stearyl alcohol, stearic acid, used in the preparation of ointments, creams, gels, suspensions, emulsions, solutions and lotions Bases such as hardened oil, gelled hydrocarbon, polyethylene glycol, liquid paraffin, squalane and the like; Such as oleic acid, isopropyl myristate, diisopropyl adipic acid, isopropyl sebacate, glycerin triisooctanoate, crotamiton, diethyl sebacate, hexyl laurate, fatty acids, fatty acid esters, aliphatic alcohols, vegetable oils Solvents and dissolution aids; Antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene and butylhydroxyanisole; Preservatives such as parahydroxybenzoic acid ester; Moisturizing agents 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, lecithin; Thickeners such as carboxyvinyl polymer, xanthan gum, carboxymethyl cellulose, carboxymethyl cellulose sodium salts, hydroxypropyl cellulose, hydroxypropyl methyl cellulose; In addition, various stabilizers, buffers, mating agents, suspending agents, emulsifiers, fragrances, preservatives, dissolution aids, and other suitable additives may be blended.
또한, 필요에 따라 안정제, 보존제, 흡수 촉진제, pH 조정제, 그 밖의 적당한 첨가제를 배합할 수 있다.Moreover, a stabilizer, a preservative, an absorption promoter, a pH adjuster, and other suitable additives can be mix | blended as needed.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 및 발모 또는 육모 촉진용 화장료 조성물을 제공한다.In addition, the present invention provides a cosmetic composition for preventing or improving hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
상기 화장료 조성물은 피부 외용제 제형으로서 헤어토닉, 헤어크림, 헤어로션, 헤어샴푸, 헤어린스, 헤어컨디셔너, 헤어스프레이, 헤어에어졸, 포마드, 분말 젤, 헤어팩, 헤어트리트먼트, 눈썹발모제, 속눈썹 발모제, 속눈썹 영양제의 제형일 수 있으나, 이에 제한되는 것은 아니다.The cosmetic composition is a skin external preparation formulation of hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder gel, hair pack, hair treatment, eyebrow regrowth, eyelash regrowth, eyelash It may be a formulation of a nutrient, but is not limited thereto.
또한, 본 발명의 탈모 예방 또는 개선용, 발모 또는 육모 촉진용 조성물은 그 제형에 달리하여 애완동물용으로 사용할 수 있다. 예를 들어, 애완동물용 샴푸 및 애완동물용 린스 등과 같이 용액, 솔젤, 에멀젼, 오일, 왁스, 에어졸 등 다양한 형태로 제조될 수 있고, 애완동물의 피부에 자극이 적고 보습력이 탁월한 중성의 세제를 첨가하여 제조할 수 있다. In addition, the composition for preventing or improving hair loss, hair growth or hair growth promoting composition of the present invention can be used for pets different from the formulation. For example, it can be prepared in various forms such as solution, sol-gel, emulsion, oil, wax, aerosol, etc. such as pet shampoo and pet rinse. It can be prepared by addition.
또한, 본 발명의 화장료 조성물은 상기 유효성분 이외에 통상적으로 허용되는 성분들을 제한 없이 포함할 수 있으며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함할 수 있다.In addition, the cosmetic composition of the present invention may include without limitation the conventionally acceptable ingredients in addition to the active ingredient, and includes conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers. can do.
샴푸의 경우에 있어서는, 세정 성분인 합성 계면활성제와 방부제, 점증제, 점도 조절제, pH 조절제, 향료, 염료, 모발 컨디셔닝제 및 물 중 어느 하나 이상을 함유할 수 있다. 상기 합성 계면활성제 중 합성 음이온 계면활성제는 알킬 및 알킬 에테르 설페이트로서, 대표적인 예로 라우릴 황산나트륨, 라우릴 황산암모늄, 라우릴 황산 트리에탄올아민, 폴리옥시에틸렌 라우릴 황산나트륨, 폴리옥시에틸렌 라우릴 황산암모늄 등이 있다. 또한 상기 합성 계면활성제 중 합성 양쪽성 계면활성제는 알킬 베타민 및 알킬 아미도프로필 베타인으로서, 대표적인 예로는 코코디메틸 카복시메틸 베타인, 라우릴디메틸 카복시메틸 베타인, 라우릴 디메틸 알파-카복시에틸 베타인, 세틸 디메틸 카복시메틸 베타인, 코카미도 프로필 베타인 등이 있다. 상기 비이온 계면활성제는 알카놀 아미드 및 아민 옥사이드로서, 라우릴 디에틸 아민옥사이드, 야자유 알킬디메틸 아민옥사이드, 라우린산 디에탄올 아미드, 야자유 지방산 디 에탄올아미드, 야자유 지방산 모노에탄올아미드 등이 있다.In the case of a shampoo, any one or more of a synthetic surfactant, a preservative, a thickening agent, a viscosity adjusting agent, a pH adjusting agent, a perfume, a dye, a hair conditioner, and water, which are cleaning components, may be contained. Among the synthetic surfactants, synthetic anionic surfactants include alkyl and alkyl ether sulfates, and representative examples thereof include sodium lauryl sulfate, lauryl ammonium sulfate, lauryl sulfate triethanolamine, polyoxyethylene lauryl sulfate, and polyoxyethylene lauryl ammonium sulfate. have. Among the synthetic surfactants, synthetic amphoteric surfactants are alkyl betamin and alkyl amidopropyl betaine, and representative examples thereof are cocodimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, lauryl dimethyl alpha-carboxyethyl betaine. , Cetyl dimethyl carboxymethyl betaine, cocamidopropyl betaine and the like. The nonionic surfactants include alkanol amides and amine oxides, such as lauryl diethyl amine oxide, palm oil alkyldimethyl amine oxide, lauric acid diethanol amide, palm oil fatty acid diethanolamide, palm oil fatty acid monoethanolamide, and the like.
본 발명에서 사용되는 임의 성분으로서는 샴푸로서의 기본적 물성 및 품질을 유지하기 위한 통상적인 임의 성분으로서 당해 분야의 전문가에게 널리 공지되어 있다. 이러한 임의 성분에는 진주박 보조제, 방부제, 점중제 및 점도 조절제, pH 조절제, 향료, 염료, 모발 컨디셔닝제가 포함된다. 예를 들면 에틸렌글리콜 모노스테아레이트, 에틸렌글리콜 디스테아레이트와 같은 진주박 보조제; 파라 옥시안식향산메틸, 메틸클로로 이소치아졸리논과 메틸 이소치아졸 리논의 혼합물과 같은 방부제; 염화나트륨, 염화암모늄, 프로필렌 글리콜과 같은 점증제 및 점도 조절제; 구연산, 인산, 수산화나트륨, 수산화칼륨과 같은 pH 조절제; 폴리쿼터늄-10, 폴리쿼터늄-7, 메틸폴리실록산, 디메티콘코폴리올, 가수분해 동물단백질과 같은 모발 컨디셔닝제, 수용성 타르와 같은 염료가 사용되며, 또한 향료가 사용될 수 있다.The optional ingredients used in the present invention are well known to those skilled in the art as conventional optional ingredients for maintaining basic physical properties and quality as shampoos. Such optional ingredients include pearlescent aids, preservatives, thickeners and viscosity adjusting agents, pH adjusting agents, perfumes, dyes, hair conditioning agents. Pearlescent aids such as, for example, ethylene glycol monostearate, ethylene glycol distearate; Preservatives such as methyl paraoxycyanate, methylchloro isothiazolinone and a mixture of methyl isothiazolinone; Thickeners and viscosity modifiers such as sodium chloride, ammonium chloride, propylene glycol; PH adjusters such as citric acid, phosphoric acid, sodium hydroxide, potassium hydroxide; Dyestuffs such as polyquaternium-10, polyquaternium-7, methylpolysiloxanes, dimethiconecopolyols, hair conditioning agents such as hydrolyzed animal proteins, water soluble tars are used, and fragrance may also be used.
또한, 본 발명은 TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 및 발모 또는 육모 촉진용 식품 조성물을 제공한다.The present invention also provides a food composition for preventing or improving hair loss and promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
본 발명의 식품 조성물은 건강기능식품의 형태일 수 있으며, "건강기능식품"은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The food composition of the present invention may be in the form of a dietary supplement, and the "health supplement" refers to a food prepared and processed using raw materials or ingredients having useful functions to the human body according to Act No. 6767 of the Act on Dietary Supplement. "Functional" means ingestion for the purpose of obtaining useful effects on health use such as nutrient control or physiological action on the structure and function of the human body.
상기 식품 조성물은 식품 첨가물을 추가로 포함할 수 있으며, "식품첨가물"로서의 적합여부는 다른 규정이 없는 한 식품의약품 안정청에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The food composition may further include food additives, and the suitability as a "food additive", unless otherwise specified, according to the General Regulations of the Food Additives Code and General Test Methods, etc. Judging by the criteria.
상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀롤로오스, 구아검 등의 천연첨가물, L-글루타민산나트륨제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합 제제류들을 들 수 있다.Items listed in the "Food Additives Code" include, for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamon acid, natural additives such as navy, licorice extract, crystalline cellulose, guar gum, L- Mixed preparations, such as a glutamate sodium preparation, a noodles addition alkali preparation, a preservative preparation, and a tar pigment preparation, are mentioned.
본 발명의 유효성분이 포함된 식품으로는 빵, 떡류, 건과류, 캔디류, 초콜릿류, 츄잉껌, 쨈류와 같은 과자류 아이스크림류, 빙과류, 아이스크림 분말류와 같은 아이스크림 제품류 우유류, 저지방 우유류, 유당분해 우유, 가공유류, 산양유, 발효유류, 버터유류, 농축유류, 유크림류, 버터유, 자연치즈, 가공치즈, 분유류, 유청류와 같은 유가공품류 식육가공품, 알가공품, 햄버거와 같은 식육제품류 어묵, 햄, 소세지, 베이컨 등의 어육가공품과 같은 어육제품류 라면류, 건면류, 생면류, 유탕면류, 호화건먼류, 개량숙면류, 냉동면류, 파스타류와 같은 면류 과실음료, 채소류음료, 탄산음료, 두유류, 요구르트 등의 유산균음료, 혼합음료와 같은 음료 간장, 된장, 고추장, 춘장, 청국장, 혼합장, 식초, 소스류, 토마토케첩, 카레, 드레싱과 같은 조미식품 마가린, 쇼트닝 및 피자를 들 수 있으나, 이에 제한되는 것은 아니다.Foods containing the active ingredient of the present invention includes breads, rice cakes, dried fruits, candy, chocolates, chewing gum, confectionery such as ice cream, ice cream products such as ice cream, ice cream powder milk, low fat milk, lactose milk, Processed Milk, Goat Milk, Fermented Milk, Butter Oil, Concentrated Milk, Milk Cream, Butter Oil, Natural Cheese, Processed Cheese, Powdered Milk, Dairy Products such as Whey, Meat Products, Processed Products, Meat Products such as Hamburgers, Ham, Fish products such as sausages, bacon and other processed meat products Ramen noodles, dried noodles, raw noodles, noodle soups, delicacies, dried noodles, improved noodles, frozen noodles, pasta noodles, fruit drinks, vegetable drinks, carbonated drinks, soy milk products, Lactic acid bacteria beverages such as yogurt, beverages such as mixed drinks, soy sauce, miso, red pepper paste, chunjang, cheongukjang, mixed soy sauce, vinegar, sauces, seasoned foods such as tomato ketchup, curry, dressing, margarine, But are the teuning and pizza, without being limited thereto.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 포함할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonating agents used in the carbonated beverage. In addition, the composition of the present invention may include a pulp for the production of natural fruit juice, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical but is usually 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.
본 발명의 유효성분을 포함한 음료 조성물은 상기 단백질을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, (예를 들어, 포도당, 과당 등); 디사카라이드, (예를 들어 말토스, 슈크로스 등); 및 폴리사카라이드, (예를 들어 덱스트린, 시클로덱스트린 등)과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등)) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.The beverage composition including the active ingredient of the present invention is not particularly limited to other ingredients other than the above-mentioned protein, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the aforementioned natural carbohydrates include monosaccharides (eg, glucose, fructose, and the like); Disaccharides (eg maltose, sucrose and the like); And conventional sugars such as polysaccharides (eg dextrin, cyclodextrin, etc.), and sugar alcohols such as xylitol, sorbitol, erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have.
또한, 본 발명은 TYMP 단백질을 개체에 처리하는 단계;를 포함하는 탈모 예방 또는 치료 방법을 제공한다.The present invention also provides a method for preventing or treating hair loss, comprising the step of treating the subject with TYMP protein.
또한, 본 발명은 TYMP 단백질을 개체에 처리하는 단계;를 포함하는 탈모 개선 방법을 제공한다.In addition, the present invention provides a method for improving hair loss comprising the step of treating the subject with a TYMP protein.
또한, 본 발명은 TYMP 단백질을 개체에 처리하는 단계;를 포함하는 발모 또는 육모 촉진 방법을 제공한다.In addition, the present invention provides a method for promoting hair growth or hair growth comprising a; treating the subject with a TYMP protein.
본 발명을 실시예 및 실험예에 의하여 더욱 상세하게 설명한다. 단, 하기 실시예 및 실험예는 본 발명을 더욱 쉽게 이해할 수 있도록 예시하는 것으로 본 발명의 내용이 실시예에 의해 한정되는 것은 아니며, 이 때, 사용되는 기술용어 및 과학용어에 있어 다른 정의가 없다면, 이 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 일반적으로 이해하는 의미를 지닌다.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 more easily, and the content of the present invention is not limited by the Examples. In this case, if there is no other definition in the technical and scientific terms used, The present invention has a meaning generally understood by those skilled in the art.
실시예 1.Example 1. TYMP의 수득Obtaining TYMP
TYMP(thymidine phosphorylase) 단백질을 Peprotech에서 구입하였다. 수득한 TYMP 단백질의 아미노산 서열 및 DNA 염기서열을 분석 확인한 결과를 서열번호 1 및 2에 나타내었다.TYMPine (thymidine phosphorylase) protein was purchased from Peprotech. The results of analyzing and confirming the amino acid sequence and the DNA base sequence of the obtained TYMP protein are shown in SEQ ID NOs: 1 and 2.
실시예 2.Example 2. TYMP의 세포증식 효과 확인Confirmation of Cell Proliferation Effect of TYMP
모발 증식력을 측정하는 대표적인 in vitro 세포 실험계인 인간 모유두 세포(human dermal papilla cell, DPC) 증식 실험을 수행하였다. 실시예 1의 TYMP 단백질 1ng/ml 또는 5ng/ml을 DPC에 처리하고 40 시간 동안의 증식을 측정한 결과를 도 1에 나타내었다.Human dermal papilla cell (DPC) proliferation experiments, a representative in vitro cell test system for measuring hair proliferation, were performed. 1 ng / ml or 5 ng / ml of the TYMP protein of Example 1 was treated with DPC, and the result of measuring proliferation for 40 hours is shown in FIG. 1.
도 1에 나타낸 바와 같이, TYMP 단백질을 DPC에 처리한 경우 TYMP 단백질을 처리하지 않은 세포보다 세포증식이 증가함을 확인하였다.As shown in FIG. 1, when TYMP protein was treated with DPC, it was confirmed that cell proliferation was increased compared with cells not treated with TYMP protein.
상기 결과로부터, TYMP 단백질이 우수한 세포증식 효과를 가짐으로써 탈모 치료 또는 육모의 촉진에 활용가능함을 확인하였다.From the above results, it was confirmed that the TYMP protein has an excellent cell proliferation effect and thus can be used for hair loss treatment or promotion of hair growth.
실시예 3.Example 3. TYMP의 발모 효과 검증Validation of TYMP's hair growth effect
발모 효과 확인을 위한 실험을 위해 7주령의 C3H/HeN 마우스의 등을 제모제를 이용하여 털을 제거한 후 안정화 시켰다. 하루 경과 후, 100ng/ml의 인간 TYMP(thymidine phosphorylase) (서열번호 1) 단백질을 등에 1회 피하 주사하였다. 대조군(control)으로는 TYMP 단백질이 용해된 동일한 부피의 0.1% BSA가 포함된 PBS(phosphate buffered saline)를 피하 주사하였다. 그 후, 15일 동안 제모된 마우스의 등 부분의 발모 정도를 추적 관찰 하였다. 발모가 일어난 마우스의 등 부분을 추적 관찰한 사진을 도 2에 나타내었다. For experiments to confirm the hair growth effect, the hair of 7-week-old C3H / HeN mice was stabilized after hair removal using a depilatory agent. One day later, 100 ng / ml human thymidine phosphorylase (SEQ ID NO: 1) protein was injected subcutaneously once. As a control, phosphate buffered saline (PBS) containing 0.1% BSA in the same volume in which TYMP protein was dissolved was injected subcutaneously. Then, the degree of hair growth of the dorsal part of the depilated mice was observed for 15 days. The photograph of the back part of the mouse in which hair growth occurred is shown in FIG.
도 2에 나타낸 바와 같이, 대조군(control)에 비해 TYMP 단백질을 처리한 군에서 발모 상태가 더 우수함을 확인하였다.As shown in Figure 2, it was confirmed that the hair growth state is better in the group treated with TYMP protein than the control (control).
또한, 15일 후 새로 발모가 일어난 마우스의 등 부분을 칼을 이용하여 털을 제거한 후, 수득한 털의 무게를 측정한 결과를 도 3에 나타내었다.In addition, after removing hair using a knife on the back part of the newly growing hair after 15 days, the weight of the obtained hair was measured, and the results are shown in FIG. 3.
도 3에 나타낸 바와 같이, 측정한 발모 무게가 대조군의 경우 40mg인 것에 비해, TYMP 단백질을 처리한 군에서는 90mg으로 나타났으며, 이를 통해 TYMP 단백질을 처리한 경우에 발모 촉진 효과가 우수함을 확인하였다.As shown in FIG. 3, the measured hair growth weight was found to be 90 mg in the TYMP protein treated group, compared to 40 mg in the control group, and it was confirmed that the hair growth promoting effect was excellent when the TYMP protein was treated. .
상기 결과로부터, TYMP 단백질 성분이 우수한 발모 효과를 가지고 있어 탈모 예방 및 치료를 위한 조성물로 이용가능함을 확인하였다.From the above results, it was confirmed that the TYMP protein component has an excellent hair growth effect and can be used as a composition for preventing and treating hair loss.
이하 본 발명의 유효성분을 포함하는 탈모 예방 또는 치료용 약학적 조성물, 탈모 예방 및 개선용 화장료 조성물 및 식품 조성물의 제제예를 설명하나, 본 발명을 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter will be described a formulation example of a pharmaceutical composition for preventing or treating hair loss, a cosmetic composition for preventing and improving hair loss, and a food composition comprising the active ingredient of the present invention, but is not intended to limit the present invention, only to be described in detail. .
제제예 1. 약학적 제제의 제조Formulation Example 1 Preparation of a Pharmaceutical Formulation
1. 산제의 제조 1. Preparation of powder
TYMP 단백질 20 mg TYMP protein 20 mg
유당 100 mg Lactose 100 mg
탈크 10 mg Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
2. 정제의 제조2. Preparation of Tablets
TYMP 단백질 10 mg TYMP protein 10 mg
옥수수전분 100 mg Corn starch 100 mg
유당 100 mg Lactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.
3. 캡슐제의 제조3. Preparation of Capsule
TYMP 단백질 10 mg TYMP protein 10 mg
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
4. 주사제의 제조4. Preparation of Injectables
TYMP 단백질 10 mg TYMP protein 10 mg
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO42H2O 26 mgNa 2 HPO 4 2H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ml) 상기의 성분 함량으로 제조한다.According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).
5. 액제의 제조5. Preparation of Liquid
TYMP 단백질 20 mg TYMP protein 20 mg
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding a proper amount of lemon aroma, and then mixing the above components, adding purified water and adjusting the whole to 100 ml by adding purified water and filling into a brown bottle. The solution is prepared by sterilization.
제제예 2. 화장품 제제의 제조Formulation Example 2 Preparation of Cosmetic Formulation
1. 헤어로션 제조1. Hair Lotion Manufacturer
TYMP 단백질 0.6 중량%TYMP Protein 0.6 wt%
글리세린 5.1 중량%Glycerin 5.1 wt%
프로필렌글리콜 4.2 중량%Propylene Glycol 4.2 wt%
토코페릴아세테이트 3.0 중량%Tocopheryl Acetate 3.0 wt%
유동파라핀 4.6 중량%4.6 wt% of liquid paraffin
트리에탄올아민 1.0 중량%Triethanolamine 1.0 wt%
스쿠알란 3.1 중량%Squalane 3.1 wt%
마카다미아너트오일 2.5 중량%Macadamia Nut Oil 2.5% by weight
폴리솔베이트 60 1.6 중량% Polysorbate 60 1.6 wt%
솔비탄세스퀴롤레이트 1.6 중량%Solbitan Sesquirrolate 1.6% by weight
프로필파라벤 0.6 중량%Propylparaben 0.6 wt%
카르복실비닐폴리머 1.5 중량%Carboxy vinyl polymer 1.5 wt%
향료 미량A small amount of spices
방부제 미량Preservative traces
정제수 잔량Purified water level
2. 헤어크림 제조2. Hair Cream Manufacturing
TYMP 단백질 1.0 중량%TYMP Protein 1.0 wt%
글리세린 4.0 중량%Glycerin 4.0 wt%
바셀린 3.5 중량%Vaseline 3.5 wt%
트리에탄올아민 2.1 중량%Triethanolamine 2.1 wt%
유동파라핀 53 중량%53% by weight of liquid paraffin
스쿠알란 3.0 중량%Squalane 3.0 wt%
밀납 2.6 중량%Beeswax 2.6 wt%
토코페릴아세테이트 5.4 중량%Tocopheryl Acetate 5.4 wt%
폴리솔베이트 60 3.2 중량% Polysorbate 60 3.2 wt%
카르복실비닐폴리머 1.0 중량%Carboxy vinyl polymer 1.0 wt%
솔비탄세스퀴올레이트 3.1 중량%Sorbanthesquioleate 3.1 wt%
향료 미량A small amount of spices
방부제 미량Preservative traces
정제수 잔량Purified water level
3. 헤어샴푸 제조3. Hair Shampoo Manufacturer
TYMP 단백질 5.8 중량%TYMP Protein 5.8 wt%
소듐라우레스셀페이트 35 중량%Sodium Laures Sulfate 35% by weight
글리세린 1 중량%1% by weight glycerin
라우라마이드디이에이 3.5 중량%Lauramid Die 3.5 wt%
프로필렌글리콜 1 중량%1% by weight of propylene glycol
코카아미도프로필 베타인 1 중량%1% by weight of cocaamidopropyl betaine
세틸알코올 0.1 중량%Cetyl alcohol 0.1 wt%
글라이콜디스테아레이트 0.5 중량%0.5% by weight of glycol distearate
부틸렌클라이콜 8 중량%Butylene glycol 8% by weight
메칠파라벤 0.2 중량%Methylparaben 0.2 wt%
트리에탄올아민 0.1 중량%0.1% by weight of triethanolamine
구연산 0.1 중량%Citric Acid 0.1 wt%
폴리쿼터늄-7 0.2 중량%Polyquaternium-7 0.2% by weight
폴리커터늄-10 0.12 중량%Polycutternium-10 0.12 wt%
올리브오일피지이-7 에스터 0.2 중량%Olive Oil Fiji-7 Ester 0.2 wt%
향료 미량A small amount of spices
방부제 미량Preservative traces
정제수 잔량Purified water level
제제예 3. 식품 제제의 제조Formulation Example 3 Preparation of Food Formulation
1. 건강식품의 제조1. Preparation of health food
TYMP 단백질 100 mg TYMP protein 100 mg
비타민 혼합물 적량Vitamin Mixture
비타민 A 아세테이트 70 g70 g of vitamin A acetate
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mgVitamin B2 0.15 mg
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 g0.2 g of vitamin B12
비타민 C 10 mg Vitamin C 10 mg
비오틴 10 g10 g of biotin
니코틴산아미드 1.7 mgNicotinamide 1.7 mg
엽산 50 gFolic acid 50 g
판토텐산 칼슘 0.5 mgCalcium Pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 mgFerrous Sulfate 1.75 mg
산화아연 0.82 mgZinc Oxide 0.82 mg
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mg15 mg potassium monophosphate
제2인산칼슘 55 mgDicalcium Phosphate 55 mg
구연산칼륨 90 mg Potassium Citrate 90 mg
탄산칼슘 100 mg Calcium Carbonate 100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
2. 건강음료의 제조2. Manufacture of health drinks
TYMP 단백질 100 mg TYMP protein 100 mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B1
비타민 B2 0.3 g0.3 g of vitamin B2
물 정량Water quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above components in accordance with a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2L container, sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Claims (16)

  1. TYMP(thymidine phosphorylase) 단백질을 유효성분으로 포함하는 탈모 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating hair loss comprising TYMP (thymidine phosphorylase) protein as an active ingredient.
  2. 제1항에 있어서,The method of claim 1,
    상기 TYMP 단백질은 서열번호 1로 표시되는 아미노산으로 이루어진 것을 특징으로 하는, 탈모 예방 또는 치료용 약학적 조성물.The TYMP protein is characterized in that consisting of the amino acid represented by SEQ ID NO: 1, hair loss prevention or treatment pharmaceutical composition.
  3. 제1항에 있어서,The method of claim 1,
    상기 TYMP 단백질은 서열번호 2의 폴리뉴클레오티드에 의하여 암호화되는 것을 특징으로 하는, 탈모 예방 또는 치료용 약학적 조성물.The TYMP protein is characterized in that encoded by the polynucleotide of SEQ ID NO: 2, hair loss prevention or treatment pharmaceutical composition.
  4. 제1항에 있어서,The method of claim 1,
    상기 탈모는 남성형 탈모, 여성형 탈모, 원형 탈모 및 휴지기 탈모로 이루어지는 군에서 선택되는 1종 이상인 것을 특징으로 하는, 탈모 예방 또는 치료용 약학적 조성물.The alopecia is characterized in that at least one selected from the group consisting of male hair loss, female hair loss, circular hair loss and resting hair loss, hair loss prevention or treatment pharmaceutical composition.
  5. TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 의약외품 조성물.A quasi-drug composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
  6. 제5항에 있어서,The method of claim 5,
    상기 의약외품은 크림, 로션, 에어로졸, 샴푸, 젤 및 팩으로 이루어진 군에서 선택된 1종 이상의 제형을 갖는 것인, 탈모 예방 또는 개선용 의약외품 조성물.The quasi-drug is one having at least one formulation selected from the group consisting of creams, lotions, aerosols, shampoos, gels and packs, qualitative composition for preventing or improving hair loss.
  7. TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 화장료 조성물.Hair loss prevention or improvement cosmetic composition containing TYMP protein as an active ingredient.
  8. 제7항에 있어서, 상기 화장료 조성물은 헤어토닉, 헤어크림, 헤어로션, 헤어샴푸, 헤어린스, 헤어컨디셔너, 헤어스프레이, 헤어에어졸, 포마드, 분말 젤, 헤어팩, 헤어트리트먼트, 눈썹발모제, 속눈썹 발모제 및 속눈썹 영양제로 이루어진 군에서 선택된 1종 이상의 제형을 갖는 것인, 탈모 예방 또는 개선용 화장료 조성물.The method of claim 7, wherein the cosmetic composition is a hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder gel, hair pack, hair treatment, eyebrow hair regrowth, eyelash hair regrowth And eyelash nutrient having one or more formulations selected from the group consisting of, hair loss prevention or cosmetic composition for improvement.
  9. TYMP 단백질을 유효성분으로 포함하는 탈모 예방 또는 개선용 식품 조성물.A food composition for preventing or improving hair loss comprising TYMP protein as an active ingredient.
  10. TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 약학적 조성물.A pharmaceutical composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  11. TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 의약외품 조성물.A quasi-drug composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  12. TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 화장료 조성물.Cosmetic composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  13. TYMP 단백질을 유효성분으로 포함하는 발모 또는 육모 촉진용 식품 조성물.Food composition for promoting hair growth or hair growth comprising TYMP protein as an active ingredient.
  14. TYMP 단백질을 개체에 처리하는 단계;를 포함하는 탈모 예방 또는 치료 방법.A method for preventing or treating hair loss, comprising: treating a subject with TYMP protein.
  15. TYMP 단백질을 개체에 처리하는 단계;를 포함하는 탈모 개선 방법.Treating the TYMP protein to the subject; Hair loss improvement method comprising a.
  16. TYMP 단백질을 개체에 처리하는 단계;를 포함하는 발모 또는 육모 촉진 방법.A method for promoting hair growth or hair growth comprising the step of treating the subject with TYMP protein.
PCT/KR2017/008117 2016-08-08 2017-07-27 Pharmaceutical composition comprising thymidine phosphorylase (tymp) protein as effective ingredient for prevention or treatment of hair loss WO2018030683A1 (en)

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