Use of 1,6-fructose diphosphate or derivatives thereof

Abstract

The present invention relates to a composition for preventing white hair, promoting black hair, and preventing, improving, or treating vitiligo or hypomelanosis, which comprises 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof as an effective ingredient, aiming to solve the problem of the prior art in which the influence on melanin formation is not great and does not play a role that can give a tangible feeling. According to the present invention, 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof is contained, thus having excellent efficacy in preventing white hair, promoting black hair, and treating vitiligo or hypomelanosis.

Description

TECHNICAL FIELD

[0001] The present application relates to a composition for preventing white hair, promoting black hair, and preventing, improving, or treating vitiligo or hypochromatism, comprising 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof as an effective ingredient. BACKGROUND

[0002] White hair is a phenomenon in which hair, eyebrows, eyelashes, and the like become gray or white. It is known that the mechanism of occurrence of white hair is pigment deficiency that occurs because the number of melanocytes, which produce melanin in hair follicles, decreases and melanin cannot be transferred to surrounding keratinocytes. Pigmentation of head hair and bodily hair requires the presence of melanocytes in the hair bulb of the hair follicle. Melanin produced in the melanocytes is transferred to keratinocytes to form a hair stalk that constitutes a pigmented hair or bodily hair strand. This structure is called a "follicular pigmentation unit." Therefore, the normal cycle of melanocytes in human hair follicles requires the presence of melanocyte precursors in the upper part of the hair follicle, which can be periodically activated to regenerate the follicular pigmentation unit.

[0003] In addition, vitiligo is an acquired pigment loss disease in which depigmented spots of various sizes and shapes appear on the skin due to the loss of melanocytes. Globally, 1 to 2% of the population suffers from vitiligo, which can cause a physical appearance problem for patients and can also lead to serious psychological problems such as interpersonal relationship difficulties. Hypochromatism is a disease similar to vitiligo in histology, which shows a state in which melanin almost disappears at the lesion, but vitiligo is a self-destruction of pigment, and in contrast, hypochromatism is caused by skin diseases such as atopic dermatitis, inflammatory dermatitis, and the like.

[0004] Korean Patent Application Publication No. 10-2009-0076536 discloses an essential oil extracted from lotus for treating vitiligo and white hair. However, since the essential oil has little effect on melanin formation, it does not exert an effect that can be experienced in one's own body. Therefore, there is a need to develop a more superior composition for preventing white hair, promoting black hair, and treating vitiligo or hypochromatism.

[0005]

Prior Art Documents

[0006]

Patent Documents

[0007] (Patent Document 1) Korean Patent Publication No. 10-2009-0076536. SUMMARY

[0008] PROBLEMS TO BE SOLVED BY THE INVENTION

[0009] To solve the above problems, the present inventors repeatedly researched a substance useful for preventing white hair, promoting black hair, and preventing, ameliorating, or treating vitiligo or hypomelanosis, as a result of which they found that 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof exhibits excellent efficacy, thereby completing the present invention. Accordingly, an object of the present invention is to provide a composition for preventing white hair, promoting black hair, and preventing, ameliorating, or treating vitiligo or hypomelanosis.

[0010] TECHNICAL SOLUTION

[0011] To achieve the above object, the present invention provides a composition for preventing white hair, promoting black hair, and preventing, ameliorating, or treating vitiligo or hypomelanosis, comprising, as an effective ingredient, 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof.

[0012] ADVANTAGEOUS EFFECTS

[0013] According to the present invention, 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof is contained, and thus has excellent efficacy in preventing white hair, promoting black hair, and preventing, ameliorating, or treating vitiligo or hypomelanosis. BRIEF DESCRIPTION OF DRAWINGS

[0014] Figure 1 A graph showing the melanin synthesis promotion effect exhibited in human normal melanocytes according to the concentration of 1,6-fructose diphosphate is shown.

[0015] Figure 2 An image showing the melanin synthesis promotion effect exhibited in human normal melanocytes according to the concentration of 1,6-fructose diphosphate is shown.

[0016] Figure 3 An image showing the efficacy evaluation results of 1,6-fructose diphosphate trisodium salt on preventing white hair and promoting black hair in human hair follicles is shown. DETAILED DESCRIPTION

[0017] As to the terms used in the present specification, general terms used currently and widely are selected based on the function in the present application, but can vary according to the intention of the skilled in the art, the precedents, or the emergence of new technologies, etc. Also, in some cases, terms arbitrarily selected by the applicant are also used, in which case, the meaning will be clearly described in the corresponding description of the application. Therefore, the definition of the terms used in the present specification should be based on the meaning of the terms by using the overall content of the present specification, rather than the mere name of the terms.

[0018] Unless otherwise defined, all terms used in the present specification, including technical or scientific terms, have the same meaning as those generally understood by the one of ordinary skill in the art to which the present application pertains. Generally understood terms should be interpreted as having the same meaning as the meaning in the context of related technology and should not be interpreted as ideal or overly formal meanings unless clearly defined in the present specification.

[0019] Numerical ranges include the numerical values defined in the present specification. All maximum numerical limitations given in the present specification include all lower numerical limitations, if explicitly included lower numerical limitations. All minimum numerical limitations given in the present specification include all higher numerical limitations, if explicitly included higher numerical limitations. All numerical limitations given in the present specification include all narrower numerical ranges falling within the broader numerical limitation, if explicitly included narrower numerical ranges.

[0020] As used in the present application, the terms "comprise", "have", "contain" are general or open-ended, and do not exclude further features or method steps not mentioned. The term "or a combination thereof" used in the present application means all permutations and combinations of the multiple items listed in the term. For example, "A, B, C, or a combination thereof" means A, B, C, AB, AC, BC, or ABC, and in the case of a particular context where order is important, at least one of BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. At the same time, it is explicitly intended that the repetition of items or terms in the combination is permissible, for example, BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, etc. The skilled person should understand that, unless otherwise stated in the context, the number of items or terms in any combination is not limited.

[0021] Hereinafter, the present application will be described in more detail with reference to the embodiments and the accompanying drawings. It should be understood, however, that the present application is not limited to the following embodiments and drawings.

[0022] In one aspect, the present application provides a composition for preventing white hair or promoting black hair, which comprises, as an effective ingredient, fructose 1,6-bisphosphate or a salt, solvate, stereoisomer or hydrate thereof. In one aspect, the present application provides a composition for preventing, ameliorating or treating vitiligo or hypomelanosis, which comprises, as an effective ingredient, fructose 1,6-bisphosphate or a salt, solvate, stereoisomer or hydrate thereof. In one aspect, the present application provides a composition for promoting melanogenesis, which comprises, as an effective ingredient, fructose 1,6-bisphosphate or a salt, solvate, stereoisomer or hydrate thereof.

[0023] The fructose 1,6-bisphosphate (FBP) is an intermediate substance produced in the glycolysis process in a living organism, and is known to play a role in protecting cells in tissue damage induced by reperfusion after hypoxia or ischemia in the heart or brain [Gastroenterology, (1990) 98: 117-126]. It is also reported that the production of nitric oxide by endotoxin is inhibited in murine macrophages [Biochemical and Biophysical Research Communication, (1998) 243: 683-687]. The mechanism of action of fructose 1,6-bisphosphate in cells is not yet known, but according to the results of research to date, fructose 1,6-bisphosphate is an important substance that controls or regulates various reactions occurring in cells and participates in metabolic processes.

[0024] In the present application, 1,6-fructose diphosphate can use any of the commonly used 1,6-fructose diphosphate, including pure 1,6-fructose diphosphate and derivatives of 1,6-fructose diphosphate. This derivative can be in the form of a salt. The salt can be used in the form of a cosmetically, food and / or pharmaceutically acceptable salt, which can be an acid addition salt formed from a free acid. The acid addition salt is obtained from: inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono- and di-carboxylic acid salts, phenyl-substituted alkanoate, hydroxyalkanoate and hydroxyalkanedioate, aromatic acid, aliphatic and aromatic sulfonic acid, etc. Non-toxic organic acids such as trifluoroacetic acid, acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid, etc. The acid addition salt can be prepared by conventional methods, for example, dissolving the compound in an organic solvent such as methanol, ethanol, acetone, dichloromethane, acetonitrile, etc., adding an organic acid or an inorganic acid, and filtering and drying the resulting precipitate; or after distilling off the solvent and excess acid under reduced pressure, drying and crystallizing in an organic solvent.

[0025] The types of cosmetically, food and / or pharmaceutically non-toxic salts include: sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, fluoride, acetate, propionate, decanoate, octanoate, acrylate, formate, isobutyrate, decanoate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, benzene sulfonate, toluene sulfonate, chlorobenzene sulfonate, xylene sulfonate, phenylacetic acid, phenylpropionic acid, phenylbutyric acid, citrate, lactate, β-hydroxybutyric acid, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, etc.

[0026] In addition, the salt can be a metal salt prepared using a base. Alkali metal salts or alkaline earth metal salts, for example, can be obtained by dissolving the compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating the filtrate to dryness. At this time, as the metal salt, barium salt, dibarium salt, sodium salt, disodium salt, tetrasodium salt, potassium salt, calcium salt, dicalcium salt, dimagnesium salt, and tricyclohexylamine salt can be used. The corresponding salt can also be obtained by reacting an alkali metal salt or an alkaline earth metal salt with an appropriate negative salt (for example, silver nitrate).

[0027] In addition, the composition of the present application can contain not only a salt thereof as a form of a fructose 1,6-bisphosphate derivative, but also a solvate, a stereoisomer, a hydrate, etc. that can be prepared therefrom.

[0028] The term "solvate" refers to a compound of the present application that incorporates a stoichiometric or non-stoichiometric amount of solvent through non-covalent intermolecular forces. Preferred solvents include volatile, non-toxic, and / or acceptable for administration to humans.

[0029] The term "stereoisomer" refers to isomers that have the same molecular formula but differ in the arrangement of atoms in space. The stereoisomer can be a diasteromer or an enantiomer. The diasteromer refers to a stereoisomer that is not a mirror image of the other, and can be classified into a cis-trans isomer due to the difference in spatial arrangement of atoms. The enantiomer refers to an isomer that is like a left hand and a right hand and does not overlap with its mirror image, and is also called an optical isomer. When 4 or more substituents on a chiral center carbon are different from each other, the enantiomer is classified into R (Rectus: clockwise direction) and S (Sinister: counterclockwise direction). The present application also includes these isomers and mixtures thereof.

[0030] The term "hydrate" refers to a compound that incorporates a stoichiometric or non-stoichiometric amount of water through non-covalent intermolecular forces. The hydrate can contain 1 equivalent or more, preferably 1 equivalent to 5 equivalents of water. Such a hydrate can be prepared by crystallizing the compound of the present application in water or an aqueous solvent.

[0031] The "active ingredient" refers to an ingredient that can exhibit a desired activity or an ingredient that exhibits an activity together with a carrier that is not active by itself. The "comprising as an active ingredient" can mean comprising as an ingredient that exhibits prevention of white hair, promotion of black hair, and / or prevention, improvement, or treatment of vitiligo or hypomelanosis.

[0032] The composition of the present application can increase the content of melanin in cells, prevent the induction of white hair in advance, promote the induction of black hair, and can be effectively used as a composition for prevention, improvement, or treatment of vitiligo or hypomelanosis.

[0033] According to one embodiment of the present application, the daily administration amount of the 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof can be greater than 10 mg / kg and less than 10,000 mg / kg, wherein the daily administration amount will vary depending on the judgment of the age, sex, body weight, specific disease or pathological state, severity of the disease or pathological state, administration route, etc. of the desired subject, and determining the administration dose based on these factors is within the knowledge of one skilled in the art. More specifically, the daily administration amount can be greater than 10 mg / kg, 11 mg / kg or more, 12 mg / kg or more, 13 mg / kg or more, 14 mg / kg or more, 15 mg / kg or more, 16 mg / kg or more, 17 mg / kg or more, 18 mg / kg or more, 19 mg / kg or more, 20 mg / kg or more, 30 mg / kg or more, 40 mg / kg or more, 50 mg / kg or more, 60 mg / kg or more, 70 mg / kg or more, 80 mg / kg or more, 90 mg / kg or more, or 100 mg / kg or more; and less than 10,000 mg / kg; 9,000 mg / kg or less, 8,000 mg / kg or less, 7,000 mg / kg or less, 6,000 mg / kg or less, 5,000 mg / kg or less, 4,000 mg / kg or less, 3,000 mg / kg or less, 2,000 mg / kg or less, 1,000 mg / kg or less, 900 mg / kg or less, 800 mg / kg or less, 700 mg / kg or less, 600 mg / kg or less, 500 mg / kg or less, 400 mg / kg or less, 300 mg / kg or less, 200 mg / kg or less, or 100 mg / kg or less, but is not limited thereto. The administration can be performed in one to several times per day. For example, administration can be performed 2 to 24 times per day, 1 to 2 times every 3 days, 1 to 6 times per week, 1 to 10 times every 2 weeks, 1 to 15 times every 3 weeks, 1 to 3 times every 4 weeks, or 1 to 12 times per year. The "administration" refers to providing the composition to the subject by any suitable method, and includes administration, application, absorption, and ingestion. At this time, the subject refers to all animals to which the composition can be administered, such as humans, monkeys, dogs, goats, pigs, or mice, etc.

[0034] As the administration method, the 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof can be administered in various oral and parenteral dosage forms. In the case of dosage, diluents or excipients of commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. are used for preparation.

[0035] Solid dosage forms for oral administration include, for example, tablets, pills, powders, granules, capsules, and the like. These solid dosage forms are prepared by mixing one or more compounds with one or more excipients such as starch, calcium carbonate, sucrose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are used. Liquid dosage forms for oral administration include, for example, suspensions, elixirs, emulsions, syrups, and the like. In these liquid dosage forms, in addition to containing the usual simple diluents, various excipients such as wetting agents, sweetening agents, flavoring agents, preservatives, and the like can be included.

[0036] Formulations for parenteral administration include sterile aqueous solutions, non- aqueous solvents, suspensions, emulsions. As non-aqueous solvents, suspending agents, injectable esters such as propylene glycol, polyethylene glycol, vegetable oils such as olive oil, ethyl oleate, and the like can be used. The composition comprising the 1,6-fructose diphosphate or its salt, solvate, stereoisomer, or hydrate as an effective ingredient can be administered parenterally, and the parenteral administration can be subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. In this case, in order to prepare a dosage form for parenteral administration, the 1,6-fructose diphosphate or its salt, solvate, stereoisomer, or hydrate can be mixed with a stabilizer or a buffer in water to prepare a solution or a suspension, and then prepared into an ampoule or a vial unit administration form. The composition can be sterilized, and / or contain a preservative, a stabilizer, a wettable powder or an emulsifier, an auxiliary agent for adjusting the osmotic pressure such as a salt and / or a buffer, and other therapeutically useful substances, and can be formulated into a dosage form according to a conventional method, i.e., a mixing, granulation, or coating method.

[0037] According to one embodiment of the present application, the content of the 1,6-fructose diphosphate or its salt, solvate, stereoisomer, or hydrate can vary depending on the dosage form, use, administration frequency, and administration route. In particular, in the dosage form of the composition of the present application, when prepared as a parenteral dosage form such as an injection, or as an oral dosage form such as a food, a pill, and a syrup, the content of the effective ingredient of the present application can vary depending on the intestinal absorption rate and digestibility of the composition, and the like. However, when the composition of the present application is prepared as a skin external agent and applied topically, considering the daily administration amount, the administration amount can be greater than 60 mg and less than 60,000 mg for a subject having a body weight of 60 kg. Assuming that the daily administration amount is 100 g, the content of the effective ingredient of the present application can be greater than 0.06% by weight and less than 60% by weight based on the total weight of the composition.

[0038] According to one embodiment of the present application, the content of the 1,6-fructose diphosphate or a salt, solvate, stereoisomer or hydrate thereof can be greater than 0.06% by weight and less than 60% by weight, based on the total weight of the composition. More specifically, it can be greater than 0.06% by weight, 0.07% by weight or more, 0.08% by weight or more, 0.09% by weight or more, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, or 0.6% by weight or more; and less than 60% by weight, 59% by weight or less, 58% by weight or less, 57% by weight or less, 56% by weight or less, 55% by weight or less, 54% by weight or less, 53% by weight or less, 52% by weight or less, 51% by weight or less, 50% by weight or less, 40% by weight or less, 30% by weight or less, 20% by weight or less, 10% by weight or less, 9% by weight or less, 8% by weight or less, 7% by weight or less, 6% by weight or less, 5% by weight or less, 4% by weight or less, 3% by weight or less, 2% by weight or less, 1% by weight or less, 0.9% by weight or less, 0.8% by weight or less, 0.7% by weight or less, or 0.6% by weight or less, but is not limited thereto. Preferably, the content of the 1,6-fructose diphosphate or a salt, solvate, stereoisomer or hydrate thereof can be 1% to 10% by weight, based on the total weight of the composition.

[0039] According to one embodiment of the present application, the composition promotes melanin pigmentation of melanocytes. More specifically, the composition stimulates inactive melanocytes or melanoblasts present in the skin or hair follicle, thereby promoting differentiation, proliferation and migration, and generating melanin. As described above, the composition of the present application promotes the induction of black hair by promoting melanin pigmentation, thereby preventing the induction of white hair in advance, and can be effectively used as a composition for preventing, improving or treating vitiligo or hypomelanosis.

[0040] According to one embodiment of the present application, the white hair is caused by aging. Causes of the occurrence of white hair include stem cell loss of melanocytes, decreased activity of melanocytes and aging, and the white hair in the present application is particularly caused by aging.

[0041] According to one embodiment of the present application, the composition can be a skin external agent composition. The term "skin" refers to a tissue covering the surface of an animal body, and is used in a broad sense to include not only a tissue covering the surface of the body such as the face or the body, but also the scalp and hair.

[0042] According to one embodiment of the present application, the composition can be a cosmetic composition. The cosmetic composition can be formulated by a conventional method. Formulation can refer to the contents disclosed in the International Cosmetic Ingredient Dictionary published by The Cosmetic, Toiletry and Fragrance Association (INCI).

[0043] Specifically, the composition can be formulated as a hair conditioner, a shampoo, a hair rinse, a hair mask, a hair oil, a hair pomade, a hair cream, a hair serum, a hair gel, a hair serum, a hair spray, a hair serum, a hair ampoule, a makeup remover, a cleanser, a toner (a skin softening toner, a nutrient toner), a lotion, a cream (a nutrient cream, a massage cream), an essence, etc. The formulation can be a rinse-off type or a wash-off type, i.e., the formulation needs to be rinsed off after being applied to the hair or scalp, or can be a leave-on type or a leave-in type, i.e., the formulation remains after being applied to the hair or scalp.

[0044] According to the quality or function of the final product, the composition can further include, as necessary, a fatty substance, an organic solvent, a solubilizing agent, a condensing agent, a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizing agent, a foaming agent, a fragrance, a surfactant, a preservative, a pH adjuster, water, an ionic or non-ionic emulsifier, a filler, a metal ion chelating agent, a chelating agent, a preservative, a retarder, a humectant, an essential oil, a dye, a pigment, a hydrophilic or lipophilic active agent, any other ingredient conventionally used in cosmetics, or a supplementary agent conventionally used in the field of cosmetology or dermatology.

[0045] According to one embodiment of the present application, the composition can be a food composition. The 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof can be directly added to food or used with other food or food ingredients, and can be appropriately used according to a conventional method. The mixed amount of the active ingredient can be appropriately determined according to the purpose of use (for prevention or improvement).

[0046] The food composition can be a health functional beverage composition, which, in addition to the inclusion of the compound as an essential ingredient in a specified ratio, is not particularly limited in other ingredients, and can include various flavoring agents or natural carbohydrates, etc. as additional ingredients, similarly to conventional beverages. As examples of the above-mentioned natural carbohydrates, conventional sugars such as monosaccharides, e.g., glucose, fructose, etc.; disaccharides, e.g., maltose, sucrose, etc.; and polysaccharides, e.g., dextrin, cyclodextrin, etc., and sugar alcohols such as xylitol, sorbitol, and erythritol, etc. are included. In addition to the above, as flavoring agents, natural flavoring agents (thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.

[0047] According to one embodiment of the present application, the composition can be a pharmaceutical composition. The pharmaceutical composition can further include pharmaceutical adjuvants for adjusting osmotic pressure, such as a preservative, a stabilizer, a wettable powder or an emulsifier, a salt and / or a buffer, and other therapeutically useful substances. The pharmaceutical composition can be administered in various oral and parenteral dosage forms, the specific content of which is as described above.

[0048] In another aspect, the present application provides use of fructose 1,6-bisphosphate or a salt, solvate, stereoisomer, or hydrate thereof in the preparation of a composition for preventing or promoting black hair.

[0049] In another aspect, the present application provides use of fructose 1,6-bisphosphate or a salt, solvate, stereoisomer, or hydrate thereof in the preparation of a composition for preventing, ameliorating, or treating vitiligo or hypomelanosis.

[0050] In another aspect, the present application provides use of fructose 1,6-bisphosphate or a salt, solvate, stereoisomer, or hydrate thereof in the preparation of a composition for promoting melanogenesis.

[0051] In another aspect, the present application provides a method for preventing or promoting black hair, which includes administering a composition including fructose 1,6-bisphosphate or a salt, solvate, stereoisomer, or hydrate thereof as an effective ingredient to a desired individual.

[0052] In another aspect, the present application provides a method for preventing, ameliorating, or treating vitiligo or hypomelanosis, which includes administering a composition including fructose 1,6-bisphosphate or a salt, solvate, stereoisomer, or hydrate thereof as an effective ingredient to a desired individual.

[0053] In another aspect, the present application provides a method for promoting melanogenesis, which includes administering a composition including fructose 1,6-bisphosphate or a salt, solvate, stereoisomer, or hydrate thereof as an effective ingredient to a desired individual.

[0054] In another aspect, the present application provides fructose 1,6-bisphosphate or a salt, solvate, stereoisomer or hydrate thereof for preventing or promoting black hair.

[0055] In another aspect, the present application provides fructose 1,6-bisphosphate or a salt, solvate, stereoisomer or hydrate thereof for preventing, ameliorating or treating vitiligo or hypomelanosis.

[0056] In another aspect, the present application provides fructose 1,6-bisphosphate or a salt, solvate, stereoisomer or hydrate thereof for promoting melanogenesis.

[0057]

EXAMPLE

[0058] Hereinafter, the present application will be described in detail with reference to examples. However, the following examples are only for the purpose of helping to understand the present application comprehensively, and the content of the present application is not limited to the following examples.

[0059] [Experimental Example 1] Evaluation of the melanin synthesis promoting effect according to the concentration of 1,6-fructose diphosphate in human normal melanocytes Figure 1

[0060] 1. Evaluation method

[0061] Human normal melanocytes (Normal human epidermal melanocytes, GIBCO TM , Thermo Fisher Scientific, USA) were treated with 0 (untreated group), 0.1 ppm, 1 ppm, 10 ppm and 100 ppm of fructose 1,6-bisphosphate, respectively, and cultured for 6 days. After the culture, the cells were dissolved in IN NaOH, and the absorbance was measured at 475 nm. The amount of melanin production was expressed as a percentage relative to the absorbance (100%) of the untreated group which was not treated with fructose 1,6-bisphosphate ester. The more the absorbance increased, the higher the melanin content was. The results are shown in FIG. 1. In addition, the e-tube image of the melanin cells dissolved in NaOH is shown in FIG. 2. Figure 2 Figure 1

[0062] 2. Evaluation results

[0063] From Figure 2 and [Experimental Example 2] Evaluation of the efficacy of 1,6-fructose diphosphate trisodium salt in preventing white hair and promoting black hair in human hair follicles , it can be confirmed that fructose 1,6-bisphosphate showed an effect of promoting melanogenesis in melanocytes, and the effect was sharply increased in the 100 ppm treatment group.

[0064] Figure 3 Figure 3

[0065] 1. Isolation of human hair follicles ​​

[0066] After a 45-year-old male who experienced a symptom of alopecia underwent a hair follicle transplantation surgery, occipital scalp tissue was obtained. Using a microscope, hair follicle samples were isolated from the obtained occipital scalp tissue. Five hair follicle samples per group, a total of 3 groups (i.e., 15 samples) were prepared to perform an administration test.

[0067] 2. Culturing of hair follicles

[0068] After 500 μl of culture medium was subcloned in a 24-well plate (Nunc, Wiesbaden, Germany), 5 samples per well were cultured. At this time, the culture medium used was William's E medium (Gibco, New York, USA) containing 2 mM of L-glutamine (PAA, Coelbe, Germany), 10 μg / ml of insulin, 10 ng / ml of hydrocortisone (Sigma, St. Louis, USA), 0.1% of amphotericin B (Gibco, New York, USA), 10 μg / ml of streptomycin, and 100 U / ml of penicillin (Gibco, New York, USA). Then, treatment was simultaneously performed with 1000 μM and 100 ppm of hydrogen peroxide and 1,6-fructose bisphosphate trisodium salt (FBP-Na3H), respectively, and cultured for 3 days. In addition, a comparison was made by a group treated only with 1000 μM of hydrogen peroxide (H2O2), and a group not treated with hydrogen peroxide and 1,6-fructose bisphosphate trisodium salt was used as a control group.

[0069] 3. Observation of melanin pigments by Fontana masson staining

[0070] After the end of the drug treatment, fixation was performed with formalin, and water washing, dehydration using alcohol and xylene, and paraffin embedding were sequentially performed according to the general tissue processing procedure. An 8-μm tissue section was prepared using a microtome (Leica RM 2145, Germany), stained with Fontana masson, and photographed using a stereomicroscope (Dongwon CNS, Korea). The image is shown in Ingredients .

[0071] 4. Evaluation results

[0072] From Content (wt%) it can be confirmed that 1,6-fructose bisphosphate trisodium salt prevents the reduction of melanin production in the hair bulb of the hair follicle caused by damage by hydrogen peroxide or the like while promoting melanin production in human hair follicles, and does not have an effect of preventing white hair.

[0073] Dosage form examples of the composition according to one aspect of the present application will be described below, but can also be applied to various other dosage forms, and the description is intended to specifically describe the present application, not to limit the present application.

[0074] [Formulation Example 1] Shampoo

[0075] A shampoo was prepared according to the composition shown in Table 1 below and according to a conventional method.

[0076] [Table 1]

[0077]

[0078]

[0079] [Formulation Example 2] Hair conditioner

[0080] A hair conditioner was prepared according to the composition shown in Table 2 below and according to a conventional method.

[0081] [Table 2]

[0082] 1,6-fructose diphosphate Propylene glycol Cetyl trimethylammonium chloride 5 Cetyl alcohol 2.0 Stearyl alcohol 1.0 Mineral oil 3.0 Citric acid 3.0 Dimethicone 0.5 Preservatives, pigments and fragrances 0.2 q.s. 1.0 Purified water q.s. Ingredients Content (wt%)

[0083] [Formulation Example 3] Skin softener

[0084] A skin softener was prepared according to the composition shown in Table 3 below and according to a conventional method.

[0085] [Table 3]

[0086]

[0087]

[0088] [Formulation Example 4] Nutrition cream

[0089] A nutrition cream was prepared according to the composition shown in Table 4 below and according to a conventional method.

[0090] [Table 4]

[0091] 1,6-fructose diphosphate Beeswax Polysorbate 60 5 Sorbitan sesquioleate 4.0 Liquid paraffin 1.5 Squalane 0.5 Caprylic / capric triglyceride 5.0 Glycerin 5.0 Butylene glycol 5.0 Propylene glycol 3.0 Carboxy vinyl polymer 3.0 Triethanolamine 3.0 Preservatives, pigments and fragrances 0.1 q.s. 0.2 Purified water q.s. Ingredients Content (wt%)

[0092] [Formulation Example 5] Nutrition cream

[0093] A nutrition cream was prepared according to the composition shown in Table 5 below and according to a conventional method.

[0094] [Table 5]

[0095] 1,6-fructose diphosphate Beeswax Polysorbate 60 5 Sorbitan sesquioleate 10.0 Liquid paraffin 1.5 Squalane 0.5 Caprylic / capric triglyceride 10.0 Glycerin 5.0 Butylene glycol 5.0 Propylene glycol 5.0 Triethanolamine 3.0 Preservatives, pigments and fragrances 3.0 q.s. 0.2 Purified water q.s. Ingredients Content (wt%)

[0096] [Formulation Example 6] Massage cream

[0097] A massage cream was prepared according to the composition shown in Table 6 below and according to a conventional method.

[0098] [Table 6]

[0099]

[0100]

[0101]

Dosage Form Example 7

[0102] A hair pack was prepared according to the composition shown in Table 7 below and according to a conventional method.

[0103]

Table 7

[0104] 1,6-fructose diphosphate Polyvinyl alcohol Sodium carboxymethyl cellulose 5 Allantoin 13.0 Ethanol 0.2 Nonyl phenyl ether 0.1 Preservatives, pigments and fragrances 5.0 q.s. 0.3 Purified water q.s. Ingredients Content (g)

[0105]

Dosage Form Example 8

[0106] A powder was prepared according to the composition shown in Table 8 below and according to a conventional method.

[0107]

Table 8

[0108] 1,6-fructose diphosphate Lactose Ingredients 5 Content (mg) 1

[0109]

Dosage Form Example 9

[0110] A tablet was prepared according to the composition shown in Table 9 below and according to a conventional method.

[0111]

Table 9

[0112]

[0113]

[0114]

Dosage Form Example 10

[0115] A capsule was prepared according to the composition shown in Table 10 below and according to a conventional method. After mixing the following composition ingredients, the capsule was filled into a gelatin capsule according to a conventional capsule preparation method to prepare a capsule.

[0116]

Table 10

[0117] 1,6-fructose diphosphate Corn starch Lactose 600 Magnesium stearate 100 Ingredients 100 Content (g) 2

[0118]

Dosage Form Example 11

[0119] A drink was prepared according to the composition shown in Table 11 below and according to a conventional method.

[0120]

Table 11

[0121] 1,6-fructose diphosphate Glucose Citric acid 0.1 Purified water 10 ​ 2 ​ 100

[0122] In various aspects, the present application is directed to and includes at least the following ways.

[0123] (Method 1) A composition for preventing white hair or promoting black hair, comprising, as an effective ingredient, 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof.

[0124] (Method 2) A composition for preventing, ameliorating, or treating vitiligo or hypomelanosis, comprising, as an effective ingredient, 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof.

[0125] (Method 3) A composition for promoting melanogenesis, comprising, as an effective ingredient, 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof.

[0126] (Method 4) The composition according to any one of the methods 1 to 3, wherein the daily administration amount of the 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof is more than 10 mg / kg and less than 10,000 mg / kg.

[0127] (Method 5) The composition according to any one of the methods 1 to 4, wherein the content of the 1,6-fructose diphosphate or a salt, solvate, stereoisomer, or hydrate thereof is more than 0.06% by weight and less than 60% by weight, based on the total weight of the composition.

[0128] (Method 6) The composition according to any one of the methods 1 to 5, wherein the composition promotes melanin pigmentation of melanocytes.

[0129] (Method 7) The composition according to any one of the methods 1 to 6, wherein the white hair is caused by aging.

[0130] (Method 8) The composition according to any one of the methods 1 to 7, wherein the composition is a skin external agent composition.

[0131] (Method 9) The composition according to any one of the methods 1 to 8, wherein the composition is a cosmetic composition.

[0132] (Method 10) The composition according to any one of the methods 1 to 9, wherein the composition is a food composition.

[0133] (Method 11) The composition according to any one of the methods 1 to 10, wherein the composition is a pharmaceutical composition.

[0134] While the present application has been described with reference to the above preferred embodiments, various modifications or changes can be made without departing from the spirit and scope of the application. Accordingly, the scope of protection of the appended claims includes these modifications or changes.

Claims

1. Use of 1,6-fructose diphosphate or a salt thereof in the manufacture of a composition for promoting melanogenesis, wherein, Treatment with 100 ppm of 1,6-fructose diphosphate or a salt thereof.

2. Use according to claim 1, characterized in that, The composition promotes melanin pigmentation of melanocytes.

3. Use according to claim 1, characterized in that, The composition is a skin external agent composition.

4. Use according to claim 1, characterized in that, The composition is a cosmetic composition.

Images