WO2013157749A1 - Composition for preventing hair loss or promoting hair growth containing octaphlorethol a (opa) as active ingredient - Google Patents

Abstract

The present invention provides a composition for preventing hair loss or promoting hair growth containing octaphlorethol A (OPA) as an active ingredient. The extract of Ishige sinicola extract increases the length of hair fiber and the octaphlorethol A isolated from the Ishige sinicola extract promotes the growth of dermal papilla cells, inhibits 5α-reductase activity, and increases PGE2 production, which contribute to hair growth. Accordingly, the octaphlorethol A can be useful as a raw material for a functional cosmetic composition or pharmaceutical composition for preventing hair loss or promoting hair growth. Additionally, since octaphlorethol A is a natural material and thus edible, the composition of the present invention containing octaphlorethol A as an active ingredient has the advantage of being safe even when used for lengthy periods of time.

Description

Hair loss prevention or hair growth improvement composition containing octaprotolol A (OPA) as an active ingredient

The present invention relates to a composition for the prevention of hair loss or hair growth comprising octaphlorethol A, more specifically octaphlorethol A isolated from the extract of Ishige sinicola as an active ingredient. .

Hair loss occurs in many men and women and causes emotional distress. Hair loss has been shown to be characterized by an increase in vellus hair, shrinking hair follicles, and reduction of growing hair follicles. Androgenetic alopecia (AGA) is the most common form of hair loss that occurs in men over 40 years old. Although the development of therapeutic agents and their mechanisms have been actively conducted due to the increase of the hair loss population, it is not known exactly what causes hair loss. Currently approved by the US Food and Drug Administration (FDA) as a drug for promoting hair growth, finasteride and minoxidil are well known.

Finasteride, a substance that inhibits the activity of type II 5α-reductase, has been developed as an agent for the treatment of enlarged prostate, and is known to promote hair growth in androgenetic alopecia patients.

Minoxidil was developed as a vasodilator for the treatment of hypertension, but has been used as a hair regrowth as hirsutism has been reported as a side effect. The mechanism of action of minoxidil on the hair growth effect has not been clarified so far, but K _ATP channel opening effect, nutrient expansion through vasodilation and activation of β-catenin pathway in dermal papilla cells induce hair growth. It is thought to do. Minoxidil is also known to proliferate dermal papilla cells by lowering apoptosis of dermal papilla cells. Dermal papilla cells are mesodermal-derived fibroblasts that influence the hair cycle through the secretion of proteins such as insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), and fibroblast growth factor-7 (FGF-7). It is reported to have. In addition, some studies have reported the regulatory functions of PG pathway and PGE2 on hair growth.

On the other hand, alopecia areata is the most common autoimmune disease caused by the action of T-lymphocytes and helper T cell cytokines. TNF-α IL-6, IL-12 and pro-inflammatory cytokine have been reported to affect the immune response of helper T cells.

Although studies on the antiviral and anti-inflammatory effects of Ishige sinicola have been conducted (Choi, et al. 2011), the active ingredients have not been identified and their efficacy mechanisms have not been elucidated.

In addition, prior document 1 relates to a hair regrowth composition comprising seaweed extract in addition to red ginseng (Sophora flavescens Aiton) extract or red pepper extract, prior art 2 using the low temperature nano-extraction method, including the active ingredient extracted from Bongling, Morus bark, seaweed, etc. It relates to a hair growth promoting agent. However, the invention of both documents does not include octaphlorethol A, which is a component of the broad leaf extract fraction.

The present inventors have continuously studied the effect of preventing hair loss and improving hair growth, and found that rats of octaphlorethol A isolated from the extracts of Ishige sinicola grew the vibrissa follicles of rats and The present invention was completed by confirming the growth proliferation effect of dermal papilla cells that play an important role in hair growth.

The present invention provides a composition for preventing hair loss or improving hair growth, containing octaprotolhol A (octaphlorethol A) represented by Formula 1 as an active ingredient.

[Formula 1]

In addition, the octaphlorethol A of the present invention is characterized in that it is isolated from the extract of the broadleaf ( Ishige sinicola) .

The extract of Ishige sinicola is selected from the group consisting of water, C ₁ -C ₄ alcohol, hexane, ethyl acetate, butylene glycol, propylene glycol, glycerin, ethyl acetate, ether, chloroform and mixed solvents thereof. It may be extracted with an extraction solvent, preferably an alcohol extract, more preferably an ethanol extract.

Examples of the broad leaf extract include water and an organic solvent, and a resultant obtained by eluting the active ingredient through means such as standing, stirring, pressing or heating. It also includes a freeze-dried product obtained by lyophilizing the liquid extract obtained as described above.

In addition, any possible means for extracting the active ingredient includes all the extracted extracts, including all the processed after extraction and freeze-drying. Others include extracts obtained by conventional extraction methods such as extraction by baths or room temperature, or by conventional extraction methods described in Chinese medicine or textbooks.

The wide plate may be used without limitation, such as harvested, cultured or commercially available, and may include, for example, drying and removing the foreign matter and salt by washing with water after harvesting.

In addition, in the composition of the present invention, octaphlorethol A is preferably included in an amount of 0.01 to 70 wt% based on the total weight of the composition.

The inventors of the present application, the octaphlorethol A isolated from the extract of the broad leaf grows the length of the hair-fiber, promotes the growth of dermal papilla cells that play an important role in hair growth, 5α- It has been shown to inhibit the activity of reductase, increase PGE ₂ production, and inhibit the production of inflammatory cytokine precursors. Therefore, octaphlorethol A of the present invention can be used for promoting hair growth or preventing hair loss.

The octaprotolhol A (octaphlorethol A) can be used as a medicine, health supplements, cosmetics, food, food additives. That is, it may be used as a pharmaceutical composition, a cosmetic composition, a food composition or a food additive containing octaphlorethol A as an active ingredient.

When the composition of the present invention is used as a pharmaceutical composition, it is formulated in the form of an external preparation for skin selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, linings, pastas and cataplasmas. Can be.

When used as a cosmetic composition, hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nourishment cream, hair moisturizer cream, hair massage cream, hair wax , Hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair drier, hair preservative, hair dye, hair wave agent, hair bleach, hair gel, hair glaze, hair dresser, hair lacquer, hair It may be formulated as a moisturizer, hair mousse or hairspray.

Hair loss prevention or hair growth improving composition containing octaphlorethol A according to the present invention has the function of promoting the growth of hair papilla cells to grow the length of the hair fiber, play an important role in hair growth, 5α-reduction Inhibitory activity of enzyme activity and PGE ₂ production proliferation ability. Therefore, since it shows a useful effect in preventing hair loss and / or hair growth, octaphlorethol A of the present invention will be useful as a raw material of the functional cosmetic composition or pharmaceutical composition for hair loss prevention / hair growth improvement . In particular, since the octaphlorethol A (octaphlorethol A) isolated from the extract of the broadleaf of the present invention is edible as a natural substance, the composition of the present invention comprising it as an active ingredient has a safe advantage even for long-term use.

Figure 1 shows the structure of octaphlorethol A of the present invention.

Figure 2 is the result of measuring the hair growth promoting effect of the extract of broadleaf. (Data is shown as mean ± SE for three separate experimental groups. ^* P <0.05 vs. control)

FIG. 3 is a graph showing the efficacy of octaphlorethol A on dermal papilla cells isolated from the extract of broadleaf. (Data is expressed as mean ± SD, ^* P <0.05 , ^** P <0.01 , ^** P <0.001 vs. control)

Figure 4 is a graph showing the efficacy of 5α-reductase activity of rat prostate of octaphlorethol A isolated from the extract of the broad leaf. (Data is expressed as mean ± SD, ^* P <0.05 , ^** P <0.01 , ^** P <0.001 vs. control)

Figure 5 is a graph showing the efficacy of PGE ₂ production activity of octaphlorethol A isolated from the extract of the broad leaf. (Data is expressed as mean ± SD, ^* P <0.05 , ^** P <0.01 , ^** P <0.001 vs. control)

All technical terms used in the present invention, unless defined otherwise, have the following definitions and conform to the meaning as commonly understood by those skilled in the art. Also described herein are preferred methods or samples, but similar or equivalent ones are within the scope of the present invention. The contents of all publications described herein by reference are incorporated into the present invention.

The term "about" means 30, 25, 20, 25, 10, 9, 8, 7, 6, 5, by reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight, or length. By amount, level, value, number, frequency, percentage, dimension, size, amount, weight or length, varying by 4, 3, 2 or 1%.

Throughout this specification, the terms “comprises” and “comprising”, unless otherwise indicated in the context, include a given step or component, or group of steps or components, but any other step or component, or It is to be understood that it does not exclude a step or group of components.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

The present inventors have investigated the hair growth efficacy of octaphlorethol A isolated from the extract of the broad leaf using in vitro experimental methods, and has been shown to play a very important role in hair growth. Confirmed. Accordingly, the present invention provides a composition for the prevention of hair loss or hair growth improvement containing octaphlorethol A as an active ingredient.

The Ishige sinicola is an annual brown algae belonging to the Phaeophyta, Phaeophyceae, Chordariales, and Ishigeaceae. This young generation alternates with the fronds consisting of milk tissues formed with different cell lines and attached to each other. The stellate is lobe and lobes are branched. Habitat inhabits temperate intertidal zones in the tropics. In Korea, it is known to be distributed throughout the southern coast and Jeju Island.

In the present invention, Ishige sinicola is extracted with an alcohol solvent, and further fractionated with dichloromethane, ethyl acetate, and water, and the fractions or compounds obtained through a sequential small fraction process are measured. Ethyl acetate fractions of or their small fractions confirmed that the most excellent hair growth effect was completed the present invention.

The strips can be purchased commercially and used, preferably dried sufficiently before extraction with a solvent. In one preferred embodiment, the dried broadleaf is refluxed with alcohol, preferably ethanol, and the extraction frequency is 1-5 times, preferably 3 times. After collecting all the extracts, the concentrated process, the concentrated extracts are suspended in water and then extracted sequentially in the order of dichloromethane, ethyl acetate and water to obtain each fraction.

It was confirmed that the ethyl acetate fraction component of the fraction is excellent in hair growth promoting effect, the fraction component showing an excellent effect on promoting hair growth was octaphlorethol A (octaphlorethol A) represented by the following formula (1).

[Formula 1]

Pharmaceutical composition

The composition of the present invention may be a pharmaceutical composition comprising octaphlorethol A as an active ingredient and a pharmaceutically acceptable carrier.

The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant may include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, Lubricants, flavors and the like can be used.

The pharmaceutical composition may be preferably formulated into a pharmaceutical composition including one or more pharmaceutically acceptable carriers in addition to the above-described active ingredient for administration.

The formulation form of the pharmaceutical composition is not particularly limited, and may be preferably formulated according to each disease or component using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA by appropriate methods in the art. have.

In one embodiment of the present invention, the pharmaceutical composition of the present invention may be a topical skin composition. The external skin pharmaceutical composition of the present invention is a skin external preparation having a skin protection effect from ultraviolet rays in the form of an external skin preparation of cream, gel, patch, spray, ointment, warning agent, lotion, linen, pasta or cataplasma. It can be prepared and used as a pharmaceutical composition, but is not limited thereto.

The preferred dosage of the pharmaceutical 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, and may be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 10 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

Cosmetic composition

In addition, the composition of the present invention can be used in a variety of hair cosmetics having a hair loss prevention and hair growth promoting effect comprising octaphlorethol A (octaphlorethol A) as an active ingredient.

According to a preferred embodiment of the present invention, the content of octaphlorethol A is 0.01 to 70% by weight, preferably 0.1 to 50% by weight based on the total weight of the composition. When the content of the octaphlorethol A is less than 0.01% by weight, the effect of preventing or reducing hair loss is greatly reduced, and when it exceeds 70% by weight, skin irritation may occur, and formulation problems may occur. have.

As a product to which the cosmetic composition of the present invention can be added, for example, hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream , Hair Moisture Cream, Hair Massage Cream, Hair Wax, Hair Aerosol, Hair Pack, Hair Nutrition Pack, Hair Soap, Hair Cleansing Foam, Hair Oil, Hair Dryer, Hair Preservative, Hair Dye, Hair Wave, Hair Bleach, Hair Gel, Cosmetics such as hair glaze, hair dresser, hair lacquer, hair moisturizer, hair mousse or hair spray and the like.

When the composition of the present invention is made of a cosmetic composition, the composition of the present invention may include not only the above-mentioned broadleaf extract fraction components, but also components commonly used in cosmetic compositions, such as water-soluble vitamins, oil-soluble vitamins, polymer peptides, And a composition selected from the group consisting of polymeric polysaccharides, sphingolipids, and seaweed extracts.

The water-soluble vitamins may be any compound that can be incorporated into cosmetics, but preferably vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, and the like. Their salts (thiamine hydrochloride, sodium ascorbate salt, etc.) and derivatives (ascorbic acid-2-sodium phosphate salt, ascorbic acid-2-magnesium phosphate salt, etc.) may also be used in the water-soluble vitamins that can be used in the present invention. Included. The water-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microorganism culture, enzyme or chemical synthesis.

The oil-soluble vitamin may be any compound that can be formulated into cosmetics, but preferably vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), and the like. , Derivatives thereof (ascorbic palmitate, ascorbic stearate, ascorbic acid dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherolvitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantotenylethyl Ethers, etc.) are also included in the oil-soluble vitamins used in the present invention. Oil-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification of microorganism culture, enzyme or chemical synthesis.

The polymer peptide may be any compound as long as it can be incorporated into cosmetics. Preferably, collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin, and the like can be given. Polymeric peptides can be purified and obtained by conventional methods such as purification from microbial cultures, enzymatic methods or chemical synthesis methods, or can be purified and used from natural products such as dermis and pig silk such as pigs and cattle.

The polymer polysaccharide may be any compound as long as it can be blended into cosmetics. Preferably, hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt, etc.) may be mentioned. For example, chondroitin sulfate or its salt, etc. can be normally purified from a mammal or fish.

The sphingolipid may be any compound as long as it can be blended into cosmetics. Preferably, ceramide, phytosphingosine, sphingosaccharide lipid, etc. may be mentioned. Sphingo lipids can usually be purified from mammals, fish, shellfish, yeasts or plants by conventional methods or obtained by chemical synthesis.

The seaweed extract may be any compound as long as it can be blended into cosmetics. Preferably, the seaweed extract may include brown algae extract, red algae extract, green algae extract, and the like. Also, calginine, arginic acid, sodium arginate, Potassium arginate and the like are also included in the seaweed extract used in the present invention. Seaweed extract can be obtained by purification from seaweed by conventional methods.

In addition to the said essential component, you may mix | blend the cosmetics of this invention with the other components normally mix | blended with cosmetics as needed. As a compounding component, it is an oil-fat component, a humectant, an emollient, surfactant, organic and inorganic pigment, organic powder, an ultraviolet absorber, a preservative, a fungicide, antioxidant, a plant extract, a pH adjuster, alcohol, a pigment, a fragrance, a blood circulation And accelerators, cooling agents, limiting agents, purified water, and the like.

Examples of the fat or oil component include ester fats, hydrocarbon fats, silicone fats, fluorine fats, animal fats, and vegetable fats and oils.

As ester fats and oils, glyceryl tri2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl mystinate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, and stearic acid Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl acid isocetyl, isostyl acid isostearyl, isostaryl palmitate, octylate acid octyldodecyl, isostearic acid isetyl, diethyl sebacate, adipine Acid isopropyl, isoalkyl neopentane, tri (capryl, capric acid) glyceryl, trimethyl ethyl trimethylol propane, triisostearic acid trimethylol propane, tetra 2-ethylhexanoic penta erythritol Cetyl caprylate, lauric acid decyl, hexyl laurate, decyl myristin, myristin acid myristyl, myritic acid cetyl, stearyl stearate, decyl oleate, rininooleic acid , Isostearyl laurate, isotridecyl myristin, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecate oleate, octylate decyl oleate, octyl dodecyl linoleate, isopropyl isopropyl acid, 2 -Cetostearyl ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicapric acid, propylene glycol dicacapate, capric acid Propylene glycol, dicapric acid neopentyl glycol, dioctanoate neopentyl glycol, tricaprylic acid glyceryl, triundecyl glyceryl, triisopalmitinate glyceryl, triisostearate glyceryl, neopentane dodecyl Isostearyl octanoate, octyl isononate, hexyl decyl neodecanoate, octyl dodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, Sothete octylate, polyglycerol oleate, polyglycerine isostearate, triisocetyl citrate, triisoalkyl citrate, triisoctyl citrate, lauryl lactate, myristyl lactate, octyl lactate, octyl lactate Ethyl, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malic acid, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipicate, diisopropyl sebacinate, Dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, physteryl isostearate, phytic oleate, 12-Steloylhydroxystearate isocetyl, 12-Steloylhydroxystearate stearyl, 12-stealo Esters such as monohydroxystearic acid isostearyl; and the like.

Hydrocarbon-based fats and oils, such as squalene, a liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, a liquid isoparaffin, polybutene, microcrystal wax, and a vaseline, etc. are mentioned as a hydrocarbon-type fats and oils.

Examples of the silicone-based oils and fats include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane, methylcetyloxysiloxane copolymer, dimethylsiloxane and methylsteoxysiloxane copolymer, and alkyl. Modified silicone oil, amino modified silicone oil and the like.

Perfluoro polyether etc. are mentioned as fluorine-based fats and oils.

Animal or vegetable oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, soybean oil, soybean oil, corn oil, rapeseed oil, almond oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil. , Cottonseed oil, Palm oil, Cucumber nut oil, Wheat germ oil, Rice germ oil, Shea butter, Walnut colostrum oil, Marker demia nut oil, Meadow home oil, Egg yolk oil, Uji, Horse oil, Mink oil, Orange rape oil, Jojoba oil And animal or plant fats and oils such as candeler wax, carnava wax, liquid lanolin and hardened castor oil.

Examples of the moisturizing agent include a water-soluble low molecular moisturizer, a fat-soluble molecular moisturizer, a water-soluble polymer, and a fat-soluble polymer.

Water-soluble low molecular humectants include serine, glutamine, sorbitol, mannitol, pyrrolidone-sodium carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (polymerization degree n = 2 or more), polypropylene Glycol (polymerization degree n = 2 or more), polyglycerol B (polymerization degree n = 2 or more), lactic acid, lactic acid salt, etc. are mentioned.

Examples of the fat-soluble low molecular humectants include cholesterol and cholesterol esters.

Examples of the water-soluble polymer include carboxyvinyl polymer, polyasparaginate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water soluble chitin, chitosan, and dextrin. Can be.

Examples of the fat-soluble polymers include polyvinylpyrrolidone-eicosene copolymers, polyvinylpyrrolidone-hexadecene copolymers, nitrocellulose, dextrin fatty acid esters, polymer silicones, and the like.

Examples of the emollient include long-chain acyl glutamic acid cholesteryl esters, hydroxy stearic acid cholesterol, 12-hydroxystearic acid, stearic acid, rosin acid, lanolin fatty acid cholesteryl esters, and the like.

As surfactant, nonionic surfactant, anionic surfactant, cationic surfactant, amphoteric surfactant, etc. are mentioned.

As the ionic surfactant, self-emulsifying glycerin monostearate, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerol fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE Glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hardened castor oil, POE castor oil, POE / POP (polyoxyethylene polyoxypropylene) copolymer, POE / POP alkyl ether, polyether modified silicone, lauric acid Alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, etc. are mentioned.

Ionic surfactants include fatty acid soaps, alpha-acyl sulfonates, alkyl sulfonates, alkyl allyl sulfonates, alkyl naphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkylphosphates, and alkylamides. Phosphates, alkyloylalkyltaurine salts, N-acylamino acid salts, POE alkyl ether carboxylate salts, alkyl sulfosuccinate salts, sodium alkyl sulfo acetates, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like. have.

As cationic surfactant, alkyl trimethylammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium bromide, behenyl trimethyl ammonium chloride, chloride Benzalkonium, diethylaminoethyl stearate, dimethylaminopropyl stearate, lanolin derivatives, quaternary ammonium salts, and the like.

Examples of amphoteric surfactants include the carboxybetaine type, the amide betain type, the sulfobetain type, the hydroxysulfobetain type, the amide sulfobetain type, the phosphobetaine type, the aminocarboxylate type, the imidazoline derivative type, and the amideamine type. An amphoteric surfactant etc. are mentioned.

Organic and inorganic pigments include silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium film mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide Inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine, and composites thereof; Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluorine resin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene, styrene copolymer, Organic pigments such as silk powder, cellulose, CI pigment yellow, CI pigment orange, and composite pigments of these inorganic pigments and organic pigments;

As organic powder, Metal soaps, such as a calcium stearate; Alkyl phosphate metal salts such as zinc sodium cetyl acid, zinc lauryl acid and calcium laurate; Acylamino acid polyvalent metal salts such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroylglycine calcium; Amide sulfonic acid polyvalent metal salts, such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; N-epsilon-lauroyl-L-lysine, N-epsilon-palmitolyzine, N-alpha-paratoylol nitin, N-alpha-lauroyl arginine, N-alpha-cured fatty acid acyl arginine Acyl basic amino acids; N-acylpolypeptides, such as N-lauroyl glycyl glycine; Alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid; Polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene-styrene copolymer, ethylene tetrafluoride and the like.

Examples of the ultraviolet absorber include paraaminobenzoic acid, ethyl paraaminobenzoate, amyl paraaminobenzoic acid, octyl paraaminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylic acid and benzyl cinnamic acid. , Paramethoxy cinnamic acid-2-ethoxyethyl, paramethoxy cinnamic acid octyl, diparamethoxy cinnamic acid mono-2-ethylhexaneglyceryl, paramethoxy cinnamic acid isopropyl, diisopropyl diisopropyl cinnamic acid ester mixture, wuro Cananoic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and salts thereof, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium sulfonate, dihydroxybenzophenone , Tetrahydroxybenzophenone, 4- tert -butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino- p- (carbo-2'-ethylhexyl-1'-oxy) -1 , 3,5-triazine, 2- (2-hi And the like can be mentioned hydroxy-5-methylphenyl) benzotriazole.

Examples of fungicides are hinokithiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, jinxylthione, benzalkonium chloride, and photosensitive Sodium No. 301, sodium mononitrohydrol, undecylenic acid, and the like.

Examples of the antioxidant include butylhydroxyanisole, propyl gallic acid, and erythorbic acid.

Examples of the pH adjuster include citric acid, sodium citrate, malic acid, sodium malate, fmaric acid, sodium pmarate, succinic acid, sodium succinate, sodium hydroxide, sodium dihydrogen phosphate, and the like.

Examples of the alcohol include higher alcohols such as cetyl alcohol.

Moreover, the compounding component which may be added other than this is not limited to this, Moreover, Although all said components can be mix | blended within the range which does not impair the objective and effect of this invention, Preferably it is 0.01-5 weight% with respect to a total weight, More preferably, it is compounded at 0.01-3 weight%.

The cosmetic of the present invention may take the form of a solution, an emulsion, a viscous mixture, or the like.

Ingredients included in the cosmetic composition of the present invention may include components commonly used in cosmetic compositions in addition to the extract as an active ingredient, for example, conventional auxiliary agents such as stabilizers, solubilizers, vitamins, pigments and flavorings. And carriers.

The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, and includes, for example, milky lotion, cream, lotion, pack, foundation, lotion, essence, hair cosmetic, and the like.

When the formulation of the present invention is a paste, cream or gel, animal carriers, vegetable fibers, waxes, paraffins, starches, tracantes, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide, etc. may be used as carrier components. Can be.

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

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

When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspension agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline Cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

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

Food composition

The composition of the present invention may also be a food composition, which contains not only octaphlorethol A, an active ingredient, but also various flavors or natural carbohydrates as additional ingredients, like conventional food compositions. It may contain.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The aforementioned flavoring agents can advantageously be used natural flavoring agents (tautin), stevia extracts (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).

The food composition of the present invention may be formulated in the same manner as the pharmaceutical composition, used as a functional food, or added to various foods. Foods to which the composition of the present invention may be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice creams, alcoholic beverages, vitamin complexes, and health supplements. There is this.

In addition, the food composition is a nutrient, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, such as octaphlorethol A as an active ingredient, flavoring agents such as colorants and neutralizing agents (cheese, chocolate, etc.) , Pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. In addition, the food composition of the present invention may contain a fruit flesh for producing natural fruit juice and fruit juice beverage and vegetable beverage.

Octaproretol A (octaphlorethol A), an active ingredient of the present invention, is a natural substance and has almost no toxicity and side effects, so it can be used safely even when taken for a long period of time to prevent hair loss or promote hair growth. The health functional food of the present invention can be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like.

In the present invention, "health functional food" refers to a food prepared and processed using raw materials or ingredients having functional properties useful for the human body according to the Health Functional Food Act No. 6767, and nutrients for the structure and function of the human body. It is meant to be consumed for the purpose of regulating or obtaining a useful effect for health use such as physiological action.

The health functional food of the present invention may include a conventional food additive, and the suitability as a food additive, unless otherwise specified, in accordance with the General Regulations of the Food Additives and General Test Methods approved by the Food and Drug Administration, etc. Judging by the standards and standards.

Examples of the items listed in the "Food Additive Revolution" include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid and cinnamic acid; Natural additives such as dark blue pigment, licorice extract, crystalline cellulose, high color pigment and guar gum; And mixed preparations such as sodium L-glutamate, algae additives, preservatives and tar dyes.

For example, the health functional food in the form of tablets is granulated mixture in a conventional manner by mixing the explosive extract, the active ingredient of the present invention with excipients, binders, disintegrants and other additives, and then compression-molded with a lubricant Alternatively, the mixture may be compression molded directly. In addition, the health functional food in the form of tablets may contain a mating agent or the like as necessary.

Hard capsules among the health functional foods in the form of capsules may be prepared by filling a mixture of octaphlorethol A, an active ingredient of the present invention, with an additive, such as an excipient, in a conventional hard capsule. A mixture of proletol A (octaphlorethol A) mixed with additives such as excipients may be prepared by filling a capsule base such as gelatin. The soft capsule agent may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, as necessary.

The health functional food in a cyclic form may be prepared by molding a mixture of an octaphlorethol A, an active ingredient of the present invention, an excipient, a binder, a disintegrant, and the like by a conventionally known method. It may be coated with sugar or other coatings, or the surface may be coated with materials such as starch or talc.

The health functional food in the form of granules may be prepared by granulation of a mixture of octaphlorethol A, an active ingredient of the present invention, an excipient, a binder, a disintegrant, and the like by a conventionally known method. Flavoring agents, mating agents and the like.

The health functional food may be beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements.

As described above, by confirming that the octaproloretolol A (octaphlorethol A) isolated from the extract of the broadleaf of the present invention exhibits the effect of inducing hair follicles to the growth phase through the proliferation of dermal papilla cells that play an important role in hair growth It can be used in a composition useful for preventing hair loss and improving hair growth.

The present invention specifically discloses the active ingredient and efficacy mechanism extracted from the broad leaf extract. Thus, a person skilled in the art with reference to the description herein can obtain the extract from the broadleaf using a variety of alcohol extracts, hot water extracts or other various extraction solvents known in the art, where octaphlorethol A It can be reasonably predicted that the result will have the effect of promoting hair growth or inhibiting hair loss.

Hereinafter, the present invention will be further described through examples. These examples are intended to illustrate the present invention more specifically, but the scope of the present invention is not limited to these examples.

Statistical analysis

All results were expressed as mean and standard deviation. Statistical significance test was performed by student's t test, and the p-value was less than 0.05. Statistical processing was performed using SPSS 12.0K for Windows (Release 12.0.1.SPSS Inc. USA).

 Experimental Example 1 Preparation of Broadleaf Extract

1-1. Manufacturing Process of Broadleaf Extract

Experimental materials, broad leaf, were collected from the coast of Seongsanpo, Jeju Island. The collected wide plates were washed with water to remove foreign substances, lyophilized, and then homogeneously crushed. 500 g of the pulverized broadleaf powder was put in 12 L of 80% ethanol, extracted at room temperature for 24 hours, and filtered. The broad-leaf ethanol extract was dissolved in dimethyl sulfoxide (DMSO) after removing the organic solvent by using a vacuum concentrator, and the final concentration of DMSO was not exceeded 0.01%.

1-2. Fractionation process

The broad extract was fractionated with 4L of hexane, 6L of chloroform, 8L of ethyl acetate, and 2L of water, and the ratio of ethyl acetate was the highest, and the silica gel column chromatography and HPLC (ThermoFisher Scientific, USA) system NMR analysis using the octaphlorethol A (see Fig. 1) had a purity of 95% or more. Table 1 shows nuclear magnetic resonance data of octaphlorethol A.

TABLE 1

( ¹ H and ¹³ C NMR data of octaphlorethol A in DMSO- d ₆ (500 MHz))

Experimental Example 2 Measurement of Hair Growth Efficacy of Broadspoil Extract in vitro

2-1. Isolation and Culture of Rat Nostril Hair Follicles

Three-week-old males of Wistar rats (Japan SLC, Hamamatsu, Janpan) were purchased from a central laboratory animal and anesthetized with ethyl ether, followed by cervical slaughter. Rat left and right mystacial pads were isolated and E / P buffer containing 100 units / ml penicillin-100 μg / ml streptomycin (Gibco Inc, NY, USA) [Earle's balanced salts solution (EBSS, Sigma MO, USA) + phosphate-buffered saline (PBS, Sigma MO, USA). The hair follicles were carefully separated while observing under a dissecting microscope. Until the hair follicles were separated, the separated hair follicles were put in a Petri dish containing E / P buffer and incubated for 1 hour at 37 ° C. in a 5% CO ₂ incubator. 2 mM L-glutamine (Gibco Inc, NY, USA), 10 μg / ml insulin (Sigma MO, USA), 50 nM hydrocortisone (Sigma MO, USA) and 100 units / ml penicillin-100 in each well of a 24 well plate 500 μl of William E medium (Gibco Inc, NY, USA) containing μg / ml streptomycin was added, and one hair follicle was added to one well and incubated at 37 ° C. in a 5% CO ₂ incubator. 8-12 hair follicles were used in one experimental group, and the medium was changed every 3 days during the culture. The broadleaf extract (1, and 10 μg / ml) and the positive control minoxidil were treated at a concentration of 10 μM.

2-2. Measurement of Nostril Hair Follicle Growth in Rats

The growth of nasal hair follicles of rats at 3 weeks of age was isolated and cultured for 3 weeks, and the hair follicle length was measured to determine whether the broad-leaf extract had hair growth efficacy. Nostril hair follicles in culture were photographed using a microscope (Olympus, Japan). Hair follicle length was measured using an image analyzer (DP controller; Olympus, Japan). The average value of hair follicle `length change was calculated and compared with the average length of the control group to measure the extent of growth.

2-3. Experiment result

As a result of comparing the length difference (%) of hair follicles between the control group and control group on day 21, hair fiber growth was 163.6% ( P> 0.05 ) and 1 and 10 ㎍ / ml respectively. It increased to 150.3% and the positive control 10 μM minoxidil showed 153.5% growth. The hair fiber length growth efficacy when the broad leaf extract was treated with 1 μg / ml was greater than that of the minoxidil, a positive control group. (See Figure 2)

Experimental Example 3 Proliferation Efficacy of Breast Papillary Cells

3 -One. Hair follicle papilla cells isolation and culture

Octaprotolol A (octaphlorethol A) to investigate the efficacy of the growth of hair follicle papilla cells were investigated using rat vibrissa immortalized dermal papilla cells isolated from rat whiskers. The dermal papilla cells are mesodermal-derived cells located at the base of the hair follicle and are known to act as important factors for hair formation and growth through interaction with matrix cells composed of epithelial cells.

Immortalized dermal papilla cells isolated from rat whiskers were treated with 100 units / ml penicillin-100 μg / ml streptomycin (Gibco Inc, NY, USA) and 10% heat-inactivated fetal bovine serum (FBS; Gibco Inc, NY, USA). DMEM (Hyclone Inc, USA) medium was used to culture at 37 ℃, 5% CO ₂ incubator, and subcultured once every three days. Proliferation of immortalized papilla cells isolated from rat beards was measured using MTT assay. 1.0 × 10 ⁴ cells / ml of dermal papilla cells were suspended in DMEM medium containing 1% FBS, placed in a 96 well plate, and incubated for 24 hours, followed by cultivation of the larvae extract fraction octaphlorethol A 0.001, 0,01, 0,1 And 1 μM. The minoxidil (Sigma, MO, USA), a positive control, was treated at a concentration of 10 μΜ. After incubation for 4 days, 50 μl of MTT (Sigma, MO, USA) was added and reacted for 4 hours. The supernatant was removed, 200 μl of DMSO was added to dissolve the precipitate, and the absorbance was measured at 540 nm using a microplate reader (Amersham Pharmacia Biotech, NY, USA). The average absorbance value for each sample group was obtained, and the degree of proliferation was investigated by comparing with the absorbance value of the control group.

3-2. Experiment result

As a result, when octaphlorethol A was treated at concentrations of 0.001, 0,01, 0,1, and 1 μM, 100.7%, 99.1%, 103.2% and 110.5% ( P> 0.05 ), respectively, compared to the control group. The positive control group, 10 μM minoxidil, showed 115.2% ( P> 0.01 ) growth. (See Figure 3)

Experimental Example 4 Evaluation of 5α-Reductase Inhibition Effect

4-1. Liquid Scintillation Assay Preparation

DHT leads to gradual miniaturization of dermal papilla cells and hair follicles, inhibits hair growth, and the conversion of testosterone to DHT has been shown to be caused by 5α-reductase activity. These findings suggest that the reduction of DHT through inhibition of 5α-reductase activity is necessary for hair growth. Therefore, we investigated whether octaphlorethol A, isolated from broad leaf extract, had a 5α-reductase inhibitory effect, which plays an important role in hair growth, using coenzymes of SD rat prostate at 7-8 weeks of age.

Seven to eight week old male rats were anesthetized with ethyl ether, and then cervical slaughtered to remove the prostate gland and stored in liquid nitrogen. The prostate was added to a homogenizer buffer (20 mM potassium phosphate buffer pH6.6, 0.32 M sucrose, 1 mM dithiothreitol (DTT), 0.2 mM PMSF) and ground using a Polytron homogenizer (Brinkman instruments, Wesrbury, NY, USA). The pellet obtained after centrifugation (100,000 g, 60 min, 4 ° C.) was washed twice, and the homogenizer buffer was added to the suspension and used as a crude enzyme.

5α-reductase assay was performed as follows. Microtube crude enzyme and the sample and reaction buffer (40 mM potassium phosphate ( pH6.6), 200 μM NADPH, 1mM DTT, 120 nCi [1,2,6,7- 3 H] testosterone) to put the final reaction solution After adjusting to 500 μl, it was reacted at 37 ° C. for 60 minutes. 1 ml of ethyl acetate was added thereto, followed by vortex, and centrifuged (1000 g, 5 minutes) to obtain a supernatant. After transferring to a new microtube, it was completely dried using a heating plate (60 ° C.). 50 μl of ethyl acetate including 500 μg / ml testosterone and 500 μg / ml dihydrotestosterone (DHT) was added to the microtube, and spotted on a TLC plate. TLC plates were developed under developing solvent (50% cyclohexane, 50% ethyl acetate) and then dried. Testosterone was identified at 254 nm by UV spectrometer and DHT was confirmed by spraying 10% sulfuric acid. Radioactivity was measured using a liquid scintillation analyzer (Packard Bioscience, Meriden, USA) with 10 ml of Ultima Gold ^TM cocktail (PerkinElmer, Massachusetts, USA) after cutting out testosterone and DHT. The conversion rate of testosterone by 5α-reductase activity was calculated as the ratio [DHT / (testosterone + DHT)] × 100.

4-2. Experiment result

As a result, when using octaphlorethol A, 29.1% ( P> 0.01 ), 27.5% ( P> 0.01 ), 20.9% ( P> 0.01 ) and 0.01, 0.1, 1 and 10 μM concentrations, respectively. 12.2% ( P> 0.05 ) inhibited 5α-reductase activity (see FIG. 4).

Experimental Example 5 Evaluation of PGE2 Production Activity of Octaphlorethol A Isolated from Broadleaf Extract

5-1. Skin keratinocyte culture

Hair growth efficacy of octaphlorethol A was investigated by the amount of PGE ₂ produced in the HaCaT cell line, which is a keratinocyte. HaCaT cells 2.0x10 ⁵ cells / mL (96 well plate) seeding and 18h culture (37 ℃, 5% CO ₂ ) and the samples were treated for 24 hours after concentration. The supernatant in the culture was taken and PGE ₂ was quantified by ELISA.

5-2. Experiment result

Octaprotolhol A (octaphlorethol A) fraction of the broad leaf extract showed a concentration-dependent PGE ₂ production effect at 1,25 and 2.5 μg / mL (see Figure 5).

So far I looked at the center of the preferred embodiment for the present invention. Those skilled in the art will appreciate that the present invention can be implemented in a modified form without departing from the essential features of the present invention. Therefore, the disclosed embodiments should be considered in descriptive sense only and not for purposes of limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope will be construed as being included in the present invention.

Claims (7)

1. Hair loss prevention or hair growth improvement composition comprising octaprotolhol A (octaphlorethol A) represented by the formula (1) as an active ingredient.

   [Formula 1]

   
2. The method of claim 1, wherein the octaphlorethol A (octaphlorethol A) is a composition for preventing or reducing hair loss, characterized in that separated from the extract of Ishige sinicola .
3. The method of claim 2, wherein the extract of Ishige sinicola is water, alcohol of C ₁ ~ C ₄ , hexane, ethyl acetate, butylene glycol, propylene glycol, glycerin, ethyl acetate, ether, chloroform and mixtures thereof Hair loss prevention or hair growth improvement composition characterized in that extracted with an extraction solvent selected from the group consisting of a solvent.
4. According to claim 1, wherein the octaprotolol A (octaphlorethol A) is a composition for preventing or reducing hair loss, characterized in that it comprises 0.01 to 70% by weight based on the total weight of the composition.
5. The composition for preventing hair loss or improving hair growth according to any one of claims 1 to 4, wherein the composition is formulated into a pharmaceutical, cosmetic and food formulation.
6. The method of claim 5, wherein it is formulated in a pharmaceutical formulation selected from creams, gels, patches, sprays, ointments, warnings, lotions, linings, pastas and cataplasmas. Composition.
7. The method of claim 5, wherein the hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream, hair moisturizer cream, hair massage cream, hair wax, Hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair drier, hair preservative, hair colorant, hair wave agent, hair bleach, hair gel, hair glaze, hair dresser, hair lacquer, hair moisturizer Hair loss prevention or hair growth composition, characterized in that formulated in the cosmetic formulation selected from the riser, hair mousse and hair spray.

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