A pharmaceutical composition for preventing or treating hair loss, comprising Connarus semidecandrus Jack extract

Abstract

The present invention relates to a composition for preventing, improving or treating hair loss and promoting hair growth or hair regrowth, which contains an extract of Connarus semidecandrus Jack. According to the present invention, when the extract of Connarus semidecandrus Jack is administered to a testosterone-mediated alopecia animal model, hair growth is promoted, hair length and thickness are increased, the expression of androgen receptor and apoptosis-related factors is suppressed, the survival and proliferation of human dermal papilla cells are promoted, and the activity of 5-α reductase is suppressed. It has been confirmed that the extract of Connarus semidecandrus Jack of the present invention can be usefully utilized in various applications for preventing or treating hair loss and promoting hair growth or hair regrowth.

Description

Technical Field

[0001] The present invention relates to an extract of Connarus semidecandrus Jack. having a hair growth or hair growth promoting, hair loss prevention or treatment effect.

Background Art

[0002] Hair repeats a cycle in the order of anagen, catagen, and telogen. The duration of the anagen phase is 2 to 6 years, accounting for 85 to 90% of the entire hair follicle. In the case of the catagen phase, it has a duration of 2 weeks and accounts for 2 to 3% of the entire hair follicle. Finally, the telogen phase has a duration of 3 to 4 months and accounts for 10 to 15% of the entire hair follicle. Such a general cycle is repeated, and when this cycle gradually becomes shorter and the number of hairs that fall out on average about 30 to 100 per day exceeds that or fails to grow, it is called alopecia. Alopecia can be broadly classified into three types: congenital alopecia in which hair is absent from birth, acquired alopecia in which hair gradually falls out with age, and alopecia due to pathological causes, which can be classified according to symptoms. The most common type of acquired alopecia is alopecia areata, male pattern alopecia (androgenetic alopecia) caused by genetic factors and the action of androgens on hair, alopecia nervosa, pityriasis alopecia, seborrheic alopecia, perennial alopecia, senile alopecia, etc. Alopecia due to pathological causes includes postpartum alopecia, post-febrile alopecia, drug-induced alopecia, etc. Currently, the most effective drugs for preventing or treating hair loss are Minoxidil and Propecia. Minoxidil was originally a blood pressure-lowering drug, which was developed to dilate capillaries and lower blood pressure. However, it is known that as a side effect, it improves blood circulation in hair follicles, thickens vellus hair, and affects hair growth. Different from its original purpose, it is now used as a hair growth agent. However, it also affects the hair all over the body. In addition to scalp hair, the hair all over the body grows thicker and coarser. Since it also plays a role in lowering blood pressure, people with low blood pressure should refrain from using it. Since the drug is metabolized by the liver, people with liver disorders should also refrain from using it. The active ingredient of Propecia is finasteride, which was developed by Merck & Co., Inc. in the United States. This ingredient was developed to treat benign prostatic hyperplasia, but during the research process, it was revealed that it could promote hair growth, and it has since been used as a hair loss treatment. When examining the cause of hair loss, testosterone is irreversibly metabolized by 5α-reductase into dihydrotestosterone (DHT), and DHT binds to androgen receptors (AR) to exhibit many biological effects. In the hair follicles of the human body, AR is mainly distributed in dermal papilla cells. DHT binds to AR in dermal papilla cells and promotes the secretion of hair growth inhibitors such as TGF-β (transforming growth factor-beta), and such inhibitors induce the death of hair matrix cells. As a result, the growth phase of the hair follicles gradually shortens, the hair follicles are miniaturized, and hair loss is induced. Propecia suppresses hair loss by inhibiting 5α-reductase, which causes hair loss, and reducing the concentration of DHT. However, since Propecia is a male hormone, it is prohibited for women to take it, and it is known to cause side effects such as loss of libido and sexual dysfunction. Recently, depression and mood swings have been reported in patients who have taken it, and this has been added as a precaution. Therefore, there is a need to develop a hair loss treatment agent that has fewer side effects than minoxidil and Propecia and is excellent in efficacy.

Summary of the Invention

Problems to be Solved by the Invention

[0003] The inventors of the present invention were searching for substances having a hair loss treatment effect derived from natural products that are relatively safe compared to chemical substances, and confirmed that the extract of Connarus semidecandrus Jack has a hair growth or hair growth promoting, hair loss prevention or treatment effect, and completed the present invention. Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating hair loss. Another object of the present invention is to provide an external pharmaceutical composition for preventing or improving hair loss. Another object of the present invention is to provide a cosmetic composition for preventing or improving hair loss. Another object of the present invention is to provide a food composition for preventing or improving hair loss. Another object of the present invention is to provide a health functional food composition for preventing or improving hair loss. Another object of the present invention is to provide a pharmaceutical composition for promoting hair growth or hair regrowth. Another object of the present invention is to provide an external pharmaceutical composition for promoting hair growth or hair regrowth. Another object of the present invention is to provide a cosmetic composition for promoting hair growth or hair regrowth. Another object of the present invention is to provide a food composition for promoting hair growth or hair regrowth. Another object of the present invention is to provide a health functional food composition for promoting hair growth or hair regrowth. Another object of the present invention is to provide a method for treating hair loss. Another object of the present invention is to provide a method for promoting hair growth or hair regrowth.

Means for Solving the Problems

[0004] To achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating hair loss, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides an external pharmaceutical composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a cosmetic composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a food composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a health functional food composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a pharmaceutical composition for promoting hair growth, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides an external composition for pharmaceutical use for promoting hair growth, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a cosmetic composition for promoting hair growth, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a food composition for promoting hair growth, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a health functional food composition for promoting hair growth, which contains an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a method for treating hair loss, which includes the step of treating an individual with an extract of Connarus semidecandrus Jack. To achieve the above and other objects, the present invention provides a method for promoting hair growth or hair regrowth, comprising the step of treating an individual with an extract of Connarus semidecandrus Jack.

Advantages of the Invention

[0005] When the extract of Connarus semidecandrus Jack. according to the present invention was treated on a testosterone-mediated alopecia animal model, hair growth was promoted, hair length and thickness were increased, the expression of androgen receptor and apoptosis-related factors was suppressed, the survival and proliferation of human dermal papilla cells were promoted, and the activity of 5-α reductase was suppressed. As a result, the extract of Connarus semidecandrus Jack. of the present invention can be usefully utilized for various applications for preventing or treating hair loss, promoting hair growth or hair regrowth.

Brief Description of the Drawings

[0006]

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Mode for Carrying Out the Invention

[0007] Hereinafter, the present invention will be described in detail. The present invention provides a pharmaceutical composition for preventing or treating hair loss, comprising an extract of Connarus semidecandrus Jack. In addition, the present invention provides a pharmaceutical composition for promoting hair growth or hair growth, comprising an extract of Connarus semidecandrus Jack.

[0008] The Connarus semidecandrus Jack is a plant found in Laos, Malaysia, Myanmar, Vietnam, India, Cambodia and the Philippines, and is known to have anti-allergic, antioxidant, antipyretic effects, etc., and is a medicinal plant used for the treatment of horizontal roots.

[0009] However, there is still a need for many studies on the efficacy of the Connarus semidecandrus Jack, and in particular, its hair growth or hair growth promotion, hair loss prevention or treatment effects have not been reported at present. When the Connarus semidecandrus Jack extract of the present invention was treated on a testosterone-mediated alopecia animal model, hair growth was promoted, hair length and thickness were increased, the expression of androgen receptors and apoptosis-related factors was suppressed, the survival and proliferation of human dermal papilla cells were promoted, and the activity of 5-α reductase was suppressed. Therefore, the Connarus semidecandrus Jack extract according to the present invention may be provided as a composition in various forms for preventing or treating hair loss, promoting hair growth or hair growth.

[0010] In the present invention, the extract is characterized in that it is extracted from any one or more parts selected from the group consisting of the whole herb, aerial part, root, leaf, seed and flower of Connarus semidecandrus Jack.

[0011] Further, the extract may be extracted with any one solvent selected from the group consisting of water, C1 to C4 alcohols, and mixed solvents thereof, and preferably, it may be extracted with ethanol. More preferably, it may be extracted with 70% ethanol.

[0012] In one embodiment of the present invention, the Connarus semidecandrus Jack extract was produced by extracting the whole herb of Connarus semidecandrus Jack with 70% ethanol.

[0013] In addition, the Connarus semidecandrus Jack extract can be extracted using a method using an extraction device such as normal temperature extraction, supercritical extraction, high temperature extraction, high pressure extraction or ultrasonic extraction method, or a method using an adsorption resin including XAD and HP-20, etc., using a conventional extraction method in the industry. In one embodiment of the present invention, extraction was carried out using normal temperature extraction.

[0014] Further, when producing the Connarus semidecandrus Jack extract of the present invention, a filtration process, a concentration and purification process, a drying process, a freezing process, etc. may be optionally added for ease of processing, storage, etc.

[0015] The filtration process may be carried out by known filtration methods, but is not limited thereto. For example, filtration using filter paper, filter mesh or microfilter, centrifugation, and separation funnel may also be used. The concentration process may be carried out by known concentration methods, but is not limited thereto. For example, it may be concentrated using rotary vacuum, precipitation concentration, evaporation concentration, vacuum concentration, ultrafiltration method, reverse osmosis method, and centrifugation method.

[0016] The drying process may be carried out by known drying methods, but is not limited thereto. For example, it may be freeze-drying, spray-drying, or hot-air drying.

[0017] In the present invention, the term "hair loss" may belong thereto without special limitation as long as the number of hairs is less than the general number beyond the normal hair growth level. In the present invention, the hair loss is not limited thereto, and may be one or more selected from the group consisting of male pattern hair loss, female pattern hair loss, alopecia areata, and telogen effluvium. More specifically, the hair loss may belong to alopecia areata, androgenetic alopecia, telogen effluvium, traumatic, trichotillomania, or pressure alopecia including anagen effluvium, pityriasis amiantacea, syphilitic alopecia, seborrheic alopecia, symptomatic alopecia, non-scarring alopecia, scarring alopecia, and congenital alopecia.

[0018] In the present invention, the term "prevention" means any act of suppressing or delaying hair loss by administration of the composition of the present invention, and the term "treatment" means any act of improving or beneficially changing the symptoms caused by hair loss by the composition of the present invention. In the present invention, the term "hair growth" means that hair grows, and the term "hair nourishment" means making the hair grow. The effects of the composition according to the present invention also include the effects of promoting hair growth or hair nourishment.

[0019] The pharmaceutical compositions of the present invention can each be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions by ordinary methods. Examples of carriers, excipients, and diluents that may be included in the pharmaceutical composition are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When formulating, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. Such solid preparations are prepared by mixing at least one or more excipients, such as starch, calcium carbonate, sucrose, or lactose, gelatin, etc., with the Connalus semidecandrus Jack extract of the present invention. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, such as wetting agents, sweeteners, flavoring agents, preservatives, etc., may also be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. As the base of suppositories, witepsol, macrogol, tween 61, cocoa butter, laurin fat, glycerogelatin, etc. may be used.

[0020] The dosage of the pharmaceutical composition of the present invention varies depending on the age, sex, and weight of the subject being treated, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, the route of administration, and the judgment of the prescriber. Determination of the dosage based on such factors is within the level of those skilled in the art, and generally the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferable dosage is from 0.1 mg / kg / day to 1000 mg / kg / day. The administration may be once a day or divided into several times. The above dosage does not limit the scope of the present invention in any way.

[0021] The pharmaceutical composition of the present invention can be administered to mammals such as mice, livestock, and humans by various routes. In the present invention, "administration" means providing a predetermined composition of the present invention to an individual by any appropriate method. The pharmaceutical composition of the present invention may be administered through various routes including oral or parenteral, and preferably, it may be applied by parenteral administration, more preferably, by topical application by coating.

[0022] In addition to the Connalus semidecandrus Jack extract according to the present invention, the pharmaceutical composition of the present invention may further contain any compound or natural extract that has already been verified for safety for preventing, improving or treating hair loss, enhancing the effect, and is known to have an effect of preventing or treating hair loss, promoting hair growth or hair follicle growth.

[0023] In addition, the pharmaceutical composition of the present invention may be used alone for the treatment of hair loss or in combination with methods using surgery, radiotherapy, hormone therapy, chemotherapy, and biological response modifiers.

[0024] The hair to which the composition of the present invention is applied includes the hair roots and hair follicles of the head, hair, eyelashes and eyebrows, beard, armpit hair, pubic hair, and all parts of the body where there are hair roots and hair follicles.

[0025] In addition, the present invention provides an external preparation composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack.

[0026] Furthermore, the present invention provides an external preparation composition for promoting hair growth or hair regrowth, which contains an extract of Connarus semidecandrus Jack.

[0027] In the present invention, the "external preparation" is used for the purpose of treating, alleviating, treating or preventing diseases of humans and animals, and is a fiber, rubber product or similar product, or a product that has a weak effect on the human body or does not act directly on the human body and is not an instrument or machine. It means an article that falls under one of the preparations used for sterilization, insecticidal and similar uses for preventing infection. It means an article that is not an instrument, machine or device among the articles used for the purpose of diagnosing, treating, alleviating, treating or preventing diseases of humans and animals, and an article that is not an instrument, machine or device among the articles used for the purpose of pharmacologically affecting the structure and function of humans and animals, and includes external skin preparations and personal hygiene products.

[0028] When the composition of the present invention is included in an external preparation for the purpose of preventing or improving hair loss, promoting hair growth or hair regrowth, the composition may be used as it is or used together with other external preparation components, and may be appropriately used according to the usual method. The mixing amount of the active ingredient can be determined appropriately according to the purpose of use. The external preparation of the present invention is not particularly limited, but may be produced and used, for example, in the form of a cream, lotion, aerosol, shampoo, gel or pack.

[0029] In the case of creams, ointments, shampoos, gels or packs, bases such as white petrolatum, yellow petrolatum, lanolin, purified beeswax, cetyl alcohol, stearyl alcohol, stearic acid, hardened oil, gelled hydrocarbons, polyethylene glycol, liquid paraffin, squalane, etc.; solvents and solubilizing agents such as oleic acid, isopropyl myristate, glyceryl triisooctanoate, crothamide, diethyl sebacate, diisopropyl adipate, hexyl laurate, fatty acids, fatty acid esters, aliphatic alcohols, vegetable oils, etc.; antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene, butylhydroxyanisole, etc.; preservatives such as para-hydroxybenzoic acid esters, etc.; humectants such as glycerin, propylene glycol, sodium hyaluronate, etc.; surfactants such as polyoxyethylene derivatives, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, lecithin, etc.; thickeners such as carboxyvinyl polymer, xanthan gum, carboxymethyl cellulose, carboxymethyl cellulose sodium salts, hydroxypropyl cellulose, hydroxypropyl methylcellulose, etc.

[0030] In the case of an aerosol agent, bases such as white petrolatum, yellow petrolatum, lanolin, purified beeswax, cetyl alcohol, stearyl alcohol, stearic acid, hardened oil, gelled hydrocarbon, polyethylene glycol, liquid paraffin, squalane, etc. used in preparations such as ointments, creams, gels, suspensions, emulsions, solutions and lotions; solvents and solubilizing agents such as oleic acid, isopropyl myristate, diisopropyl adipate, isopropyl sebacate, glyceryl triisooctanoate, crothamide, diethyl sebacate, hexyl laurate, fatty acids, fatty acid esters, aliphatic alcohols, vegetable oils, etc.; antioxidants such as tocopherol derivatives, L-ascorbic acid, dibutylhydroxytoluene, butylhydroxyanisole, etc.; preservatives such as para-hydroxybenzoic acid esters, etc.; humectants such as glycerin, propylene glycol, sodium hyaluronate, etc.; surfactants such as polyoxyethylene derivatives, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, lecithin, etc.; thickeners such as carboxyvinyl polymer, xanthan gum, carboxymethyl cellulose, sodium carboxymethyl cellulose salts, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, etc.; furthermore, various stabilizers, buffers, flavoring agents, suspending agents, emulsifying agents, fragrances, preservatives, solubilizing agents, and other appropriate additives may be blended. In addition, stabilizers, preservatives, absorption promoters, pH adjusters, and other appropriate additives may be blended as necessary.

[0031] In addition, the present invention provides a cosmetic composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack.

[0032] At the same time, the present invention provides a cosmetic composition for promoting hair growth or hair regrowth, which contains an extract of Connarus semidecandrus Jack.

[0033] The components contained in the cosmetic composition of the present invention may include, in addition to the extract of Connarus semidecandrus Jack, components commonly used in cosmetic compositions, for example, ordinary adjuvants and carriers such as stabilizers, solubilizers, vitamins, pigments and fragrances.

[0034] The cosmetic composition of the present invention may be manufactured in any dosage form commonly manufactured in the industry, for example, emulsions, creams, lotions, packs, foundations, lotions, beauty essences, hair cosmetics, etc.

[0035] Specifically, the cosmetic composition of the present invention includes dosage forms of skin lotions, skin softeners, skin toners, astringents, lotions, milk lotions, moisture lotions, nutritional lotions, massage creams, nutritional creams, moisture creams, hand creams, foundations, essences, nutritional essences, packs, soaps, cleansing foams, cleansing lotions, cleansing creams, body lotions and body cleansers.

[0036] More preferably, it may be in the dosage form of hair tonics, hair creams, hair lotions, hair shampoos, hair rinses, hair conditioners, hair sprays, hair aerosols, pomades, powder gels, hair packs, hair treatments, eyebrow hair growth stimulants, eyelash hair growth stimulants or eyelash nutritional agents, but is not limited thereto.

[0037] When the dosage form of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, tragacanths, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talcs or zinc oxides, etc. may be used as carrier components.

[0038] When the dosage form of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as the carrier component. Particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether may further be included.

[0039] When the dosage form of the present invention is a solution or an emulsion, a solvent, a solvate or an emulsifying agent is used as the carrier component. For example, there are water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol fatty acid ester, polyethylene glycol or fatty acid ester of sorbitan.

[0040] When the dosage form of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth may be used as the carrier component.

[0041] When the dosage form of the present invention is surfactant-containing cleansing, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinate monoester, isethionic acid, an imidazolinium derivative, methyl taurate, sarcosinate, a fatty acid amide ether sulfate, an alkyl amide betaine, an aliphatic alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a lanolin derivative or an ethoxylated glycerol fatty acid ester may be used as the carrier component.

[0042] In addition to the above-mentioned active ingredients, the cosmetic composition of the present invention may further contain one or more components useful for improving the skin condition, including components for preventing, improving or treating hair loss, promoting hair growth or hair follicle growth, which exhibit the same or similar functions. Examples of such components include hyaluronic acid, butylene glycol, glycerin, amino acids, trehalose, kojic acid and its derivatives, arbutin, ascorbic acid and its derivatives, hydroquinone and its derivatives, resorcinol, 2,7-dinitroindazole, adenosine, retinol, retinyl palmitate, polyethoxylated retinamide, yeast, dipeptides, palmitoyl oligopeptide & palmitoyl tripeptide-7, acetyl hexapeptide, EGF (epidermal growth factor), or plant extracts such as citrus unshiu, rice, licorice, shea butter, aloe vera, coconut, olive, avocado, etc., but are not limited thereto.

[0043] In the present invention, when the extract of Connarus semidecandrus Jack is used as a cosmetic composition for preventing or improving hair loss, or a cosmetic for promoting hair growth or hair follicle growth, the extract of Connarus semidecandrus Jack may be added in an amount of 0.001 to 50.0% by weight, preferably 0.005 to 10.0% by weight, based on the total weight of the cosmetic composition. If the content is less than 0.001% by weight, it is difficult to expect a substantial hair growth promoting effect, and if it exceeds 50% by weight, problems such as an increase in production cost may occur compared to the cosmetic effect.

[0044] In addition, the composition for preventing or improving hair loss or promoting hair growth or hair development of the present invention can be used for pets regardless of its dosage form. For example, it may be manufactured in various forms such as solutions, hydrogels, emulsions, oils, waxes, aerosols, etc., like pet shampoos and pet rinses, and can be manufactured by adding a neutral detergent with less irritation to the pet's skin and excellent moisturizing power.

[0045] In addition, the present invention provides a food composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack.

[0046] In addition, the present invention provides a food composition for promoting hair growth or hair development, which contains an extract of Connarus semidecandrus Jack.

[0047] In addition, the present invention provides a health functional food composition for preventing or improving hair loss, which contains an extract of Connarus semidecandrus Jack.

[0048] In addition, the present invention provides a health functional food composition for promoting hair growth or hair development, which contains an extract of Connarus semidecandrus Jack.

[0049] The food composition according to the present invention includes all forms such as functional foods, nutritional supplements, health foods, health supplements, and food additives. The food compositions of the above types may be formulated in any one form selected from the group consisting of powders, tablets, capsules, pills, and liquids according to the usual methods known in the art, but are not limited thereto. They can be manufactured in various forms using methods known in the art.

[0050] For example, as a health food, the Cynanchum semidecandrum Jack extract of the present invention can be granulated, encapsulated, and powdered for ingestion, or can be manufactured and drunk in the form of tea, juice, and drinks. Further, the Cynanchum semidecandrum Jack extract of the present invention can be mixed with known substances or active ingredients known to have activity for preventing, improving, or treating hair loss and promoting hair growth or hair regrowth, and manufactured in the form of a composition.

[0051] Also, as a functional food, the Cynanchum semidecandrum Jack extract of the present invention can be added to beverages (including alcoholic beverages), fruits and their processed foods (e.g., canned fruits, bottled fruits, jams, marmalades, etc.), fish, meats and their processed foods (e.g., hams, sausage combos, etc.), breads and noodles (e.g., udon, soba, ramen, spaghetti, macaroni, etc.), fruit juices, various drinks, cookies, candies, dairy products (e.g., butter, cheese, etc.), edible vegetable oils, margarine, vegetable proteins, retort foods, frozen foods, various seasonings (e.g., miso, soy sauce, sauce, etc.), etc. for manufacturing.

[0052] In addition, the food composition of the present invention may contain ordinary food additives. Unless otherwise specified, the suitability as the "food additive" is determined according to the standards and criteria regarding the relevant items in accordance with the general rules and general test methods of the Food Additive Codex approved by the Food and Drug Safety Office. Examples of the items listed in the "Food Additive Codex" include chemical synthetic substances such as ketones, glycine, potassium citrate, nicotinic acid, cinnamic acid, natural additives such as oyster shell pigment, licorice extract, crystalline cellulose, sorghum pigment, guar gum, and mixed preparations such as sodium L-glutamate preparations, alkaline agents for noodles, preservative preparations, and tar pigment preparations.

[0053] In the food composition of the present invention, the Connarus semidecandrus Jack extract may preferably be contained in an amount of 0.00001 to 50% by weight based on the food composition. When the content is less than 0.00001% by weight, the effect is poor, and when it exceeds 50% by weight, the increase in effect is negligible compared to the amount used and it is not economical.

[0054] In addition, in order to use the Connarus semidecandrus Jack extract of the present invention in the form of a food additive, it can be produced and used in forms such as tablets, capsules, powders, granules, liquids, and pills.

[0055] When the composition of the present invention is produced as a beverage, it may contain various flavoring agents or natural carbohydrates, etc. as additional components like ordinary beverages. The above-mentioned natural carbohydrates can use monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrates is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

[0056] In addition to the above, the composition of the present invention may contain various nutritional agents, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. Additionally, the composition of the present invention may contain pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. Such components can be used independently or in combination. The ratio of such additives is not so important, but it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

[0057] In the present invention, the "health supplement food" or "health functional food" means a food manufactured and processed using raw materials and components having useful functionality for the human body according to the law on health functional foods, and "functionality" means ingesting for the purpose of regulating nutrients with respect to the structure and function of the human body or obtaining useful effects for health applications such as physiological actions.

[0058] In addition, the present invention provides a method for treating hair loss, comprising the step of treating an individual with an extract of Connarus semidecandrus Jack.

[0059] In addition, the present invention provides a method for promoting hair growth or hair regrowth, comprising the step of treating an individual with an extract of Connarus semidecandrus Jack.

[0060] The individual is preferably a mammal including humans, and is applicable without limitation to individuals requiring treatment of hair loss, hair growth, or hair regrowth.

[0061] In addition, the extract of Connarus semidecandrus Jack. of the present invention may be processed in combination with a drug or treatment method for the treatment of hair loss, hair growth or hair nourishment. When the extract of Connarus semidecandrus Jack. of the present invention is processed in combination, it may be processed simultaneously or sequentially with other drugs or treatment methods for the treatment of hair loss, hair growth or hair nourishment.

[0062] As long as the above-mentioned content of the present invention does not conflict with each other, it is equally applicable to each other, and the appropriate modifications made by those of ordinary skill in the art and implemented are also included in the scope of the present invention.

[0063] Hereinafter, the present invention will be described in detail by way of examples, but the scope of the present invention is not limited only to the following examples.

[0064] Experimental Example 1. Materials and Reagents Human hair follicle dermal papilla cells (HDP) were purchased from ATCC (the American Type Culture Collection) (Rockville, MD, USA)). Testosterone, finasteride, sesame oil, and DMSO (dimethyl sulfoxide) were purchased from Sigma (St. Louis, MO, USA). RPMI1640 medium, trypsin (0.25%), and an antibiotic (penicillin-streptomycin) solution were purchased from HyClone Laboratories (Logan, Utah, USA). CEFOgro, the HDP growth medium TMHuman Dermal Papilla Growth Medium was obtained from CEFO Co. (Seoul, Korea). Fetal Bovine Serum (FBS) was purchased from Gibco (Grand Island, NY, USA). Phosphate-buffered saline (PBS) was purchased from Samchun Pure Chemical Co. (Gyeonggi-do, Korea). TRIzol reagent was purchased from Molecular Research Center, Inc. (Cincinnati, OH, USA). Antibodies against Bcl-2 (catalog number #2876), Bax (catalog number #2772), Caspase 3 (catalog number #9662), and Cleaved Caspase 3 (catalog number #9661) were obtained from Cell Signaling Technology (Beverly, MA, USA). Antibodies against Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (catalog number #sc-47724) and Androgen receptor (AR) (catalog number #sc-7305) were obtained from Santa Cruz Biotechnology, Inc. (Dallas, TX, USA).

[0065] Experimental Example 2. Experimental Animals and Cell Culture C57BL / 6 mice (male, 5 weeks old) were purchased from Orient Bio. Additionally, the mice were bred with sufficient supply of water and food. The animal experiments of the present invention were conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee (IACUC) of Sungkyunkwan University (SKKUIACUC-2021-07-18-1). HDP cells were cultured at 37°C and 5% CO2 using HDP growth medium.

[0066] Experimental Example 3. Preparation of Animal Model An androgenic alopecia model induced by testosterone was established using C57BL / 6 mice. C57BL / 6 mice (n = 6) were divided into the following five groups: a control group (Normal group), a vehicle control group (Vehicle control group): an experimental group treated with 40 μg / kg / week of testosterone, an experimental group treated with 5 mg / day of Cs-EE (Connarus semidecandrus Jack extract according to the present invention), an experimental group treated with 10 mg / day of Cs-EE, and a positive control group: an experimental group treated with 5 mg / kg / day of finasteride. To confirm the hair growth promoting effect of Cs-EE, hair removal cream was applied to the dorsal part of each mouse, and the hair was removed twice using a shaver; 7 days and 3 days before the first testosterone treatment. After dissolving 40 μg / kg of testosterone in sesame oil, it was subcutaneously injected once a week for 4 times. Thereafter, in the case of the experimental group treated with Cs-EE, Cs-EE (1:1 ratio) diluted with PBS and DMSO was applied to the dorsal part of the mouse once a day for 3 weeks. The positive control group was treated with 5 mg of finasteride instead of Cs-EE of the present invention. After 2 days from the injection of testosterone, the mice in all experimental groups were euthanized. Thereafter, the dorsal hair of each experimental group was separated to confirm the hair type frequency and hair thickness.

[0067] Experimental Example 4. Analysis of Hair Cover Skin Ratio, Hair Type Frequency, and Hair Thickness After removing the hair of the androgenetic alopecia animal model of Example 3, dorsal skin photographs were taken weekly. Then, using Image J, the degree of hair growth was evaluated by selecting a score from 1 to 10 according to the hue of the dorsal hair growth area. Thereafter, up to 350 hairs per mouse were collected to identify four types of mouse hair (guard hair, awl hair, auchene hair, and zigzag hair).

[0068] Experimental Example 5. Hematoxylin & Eosin Staining The skin of the androgenetic alopecia animal model of Example 3 etc. was fixed in 37% formalin at 4°C for 2 days and then embedded in paraffin. After sectioning this at 4 μm, it was stained using hematoxylin and eosin to confirm hair loss.

[0069] Experimental Example 6. Ex vivo Culture of Hair Follicles of Androgenetic Alopecia Animal Models The androgenetic alopecia animal model of Example 3 was euthanized to obtain vibrissae hair follicles (n = 15). The obtained hair follicles were cultured using HDP growth medium under conditions of 37°C and 5% CO2. The medium was aspirated, and after one day, DMSO or Cs-EE 100 μg / mL was treated on the hair follicles for seeding, and then the hair length was measured every 0, 8, 16, 24, and 48 hours.

[0070] Experimental Example 7. Quantitative Real-Time PCR RNA was extracted from the skin tissue of the androgenetic alopecia animal model of Example 3. After pretreatment with 25, 50, and 100 μg / mL of Cs-EE using TRIzol reagent, total RNA was extracted from HDP cells treated with 100 nM of DTH for 24 hours. Using this, cDNA was synthesized according to the manufacturer's guidelines using a cDNA synthesis kit (Thermo Fisher Scientific). The mRNA levels of Bcl-2, Bax, and caspase-9 were confirmed by real-time PCR using SYBR premix Ex Taq (using the primers in Tables 1 and 2). At this time, the expression level of each gene was calculated based on the GAPDH expression.

[0071]

Table 1

[0072]

Table 2

[0073] Experimental Example 8. Western Blotting The skin tissue of the androgenetic alopecia animal model of Example 3 was ground in liquid nitrogen and then stored at -70°C. Then, the tissue was lysed using a lysis buffer (containing 50 mM Tris-HCl (pH 7.4), 120 mM NaCl, 25 mM β-glycerol phosphate (pH 7.5), 20 mM NaF (Sodium fluoride), 2% NP-40 (Nonidet P-40), and protease inhibitors). Subsequently, after sonication, the lysate was centrifuged at 12,000 xg for 3 minutes at 4°C. The supernatant was obtained for Western blot analysis and analyzed by 10 - 15% SDS-polyacrylamide gel electrophoresis.

[0074] The levels of AR, Bcl-2, caspase-3, cleaved caspase-3, and β-actin were confirmed by an existing well-known Western blotting method using the corresponding antibodies respectively.

[0075] Experimental Example 9. 5-α Reductase Activity analysis The entire liver of 10-week-old Sprague-Dawley male rats was excised and lysed in a lysis buffer (containing 7.5 nM K2HPO4, 3.25 nM KH2PO4, 1 mM DTT (dithiothreitol), 32 mM sucrose, 0.2 mM PMSF (phenylmethylsulfonyl fluoride), and additional protease inhibitors) to obtain 5-α reductase.

[0076] Therefore, McIlvaine buffer (pH 5.0) was immediately added to 4 μL of the enzyme extract treated with 34 mM NADPH (nicotinamide adenine dinucleotide phosphate), 0.4 mM testosterone, and a series of concentrations of Cs-EE. Then, heat was applied at 80°C for 5 minutes to stop the reaction. Additionally, the absorbance was measured at 340 nm to detect the oxidation of NADPH.

[0077] Experimental Example 10. Cell Viability analysis HDP cells were cultured in a 96-well plate at a concentration of 5×10 4 cells / mL. 50 μl of Cs-EE was treated dose-dependently in each well. After 24 hours, 10 μl of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) was added to each well and reacted for 3 hours. 100 μl of 10% SDS in 0.01 M HCl was added to each well to terminate the reaction, and formazan was dissolved for 24 hours. Subsequently, the absorbance of MTT formazan was measured at 540 nm.

[0078] Experimental Example 11. Cell Proliferation analysis Cell proliferation analysis was performed in the presence or absence of DHC (dihydrotestosterone). HDP cells were cultured in a 96-well plate at a concentration of 3×10 3 cells / mL, and the cell viability was confirmed 0, 24, 48, and 72 hours after Cs-EE treatment. The optical density was detected at 540 nm.

[0079] Experimental Example 12. Statistical analysis All experiments were independently repeated at least twice for statistical comparison of mean ± standard deviation (SD) values. For statistical comparison, the data were analyzed by t-test, and values with a P-value less than 0.05 were considered significant.

[0080] Example 1. Preparation of Connarus semidecandrus Jack. extract The Connarus semidecandrus Jack extract was obtained from the National Institute of Biological Resources of Korea under the umbrella of the Ministry of Environment and was produced by extraction with 70% ethanol. More specifically, it was produced as follows. First, the whole plant was treated with 70% ethanol at a temperature of 20 - 22°C for 24 hours for extraction. Then, ethanol was removed and concentrated under vacuum conditions of 10 hPa and 40°C using a rotary evaporator (Buchi Labortechnik AG; Pfäffikon, Switzerland). After that, the solvent was further completely removed under conditions of 5 m Torr and -85°C, and then the extract (named Cs-EE) was lyophilized and stored.

[0081] Example 2. Confirmation of the hair growth promotion and hair growth enhancing effects of Cs-EE in a hair loss animal model The experimental timeline for confirming the hair growth promotion and hair growth enhancing effects of Cs-EE according to the present invention in an androgenetic alopecia animal model induced by testosterone is as shown in FIG. 1.

[0082] As shown in FIG. 2, in the experimental group treated with Cs-EE 3 weeks after hair shaving, the skin color was almost completely restored, showing significant regrowth. Also, it recovered earlier than the vehicle experimental group (Vehicle Testosterone 40 μg / kg / week experimental group) which is the negative control group and the finasteride-treated experimental group (Finasteride 5 mg / kg / day experimental group) which is the positive control group. At the first week, in the negative control group (Vehicle) and the finasteride experimental group, most of the shaved skin remained hairless, while the experimental group treated with Cs-EE according to the present invention showed obvious hair growth. Based on the collected photographs in FIG. 2, the skin color score was measured by determining the hue from pink to black, and this is shown in FIG. 3a. As a result, the skin color score of the Cs-EE-treated experimental group showed a tendency similar to that of the normal group (Normal). Also, it showed significantly higher scores at all time points compared to the negative control group (Vehicle) or the finasteride-treated experimental group. Thereby, it was confirmed that Cs-EE of the present invention has a stable hair regrowth promoting effect similar to that of the normal group.

[0083] In addition, as shown in Fig. 3b, it was confirmed that the frequency of hair types also changed significantly. In the case of the negative control group (Vehicle), it was possible to confirm that the number of thin zigzag-shaped hairs increased by testosterone treatment. However, it was confirmed that it was alleviated by Cs-EE treatment according to the present invention, and in particular, the effect of the Cs-EE 10 mg / kg treatment experimental group was the most excellent. In addition, photographs of the hair types of each experimental group are shown in Fig. 4a. As a result, in the negative control group (Vehicle), the hair thickness became thinner compared to the normal group, whereas in the Cs-EE treatment experimental group according to the present invention, it was confirmed that the hair thickness increased. In addition, based on the hair type photographs of each experimental group, the thickness of each hair type was measured and shown in Fig. 4b. As a result, it was confirmed that the Cs-EE treatment experimental group according to the present invention restored the hair thickness that had been decreased by testosterone. In addition, as shown in Fig. 4c, it was confirmed that the total hair thickness of the Cs-EE treatment experimental group according to the present invention also recovered.

[0084] Example 3. Histological analysis of mouse hair follicles and confirmation of the hair protection and growth promoting effects of Cs-EE in in vitro culture Through histological analysis of mouse hair follicles, the hair growth promoting effect of Cs-EE according to the present invention was confirmed. As shown in Fig. 5a, the hair follicles of the experimental group treated with testosterone showed an empty space without hair fibers (indicated by black arrows). However, as shown in Figs. 5a and 5b, it was confirmed that the Cs-EE treatment experimental group promoted the development of new hair fibers on the surface of the epidermis.

[0085] In addition, the hair growth promoting effect of Cs-EE according to the present invention could also be confirmed in in vitro culture of hair follicles. As shown in Figs. 5c and d, as a result of culturing hair follicles for 48 hours with or without treatment with 100 μg / ml of Cs-EE, when not treated with Cs-EE, the hair length reached less than 1000 μm, but when treated with Cs-EE, the hair length became longer than 1200 μm. Therefore, it was confirmed that Cs-EE according to the present invention suppresses testosterone-mediated hair loss and induces hair growth by this means.

[0086] Example 4. Confirmation of the mechanism for the hair protection and growth promoting effects of Cs-EE To confirm the mechanism for the hair loss prevention effect of Cs-EE, the level of AR protein in the back skin of an androgenetic alopecia animal model induced by testosterone was confirmed by Western blot. As a result, as shown in FIG. 6, Cs-EE according to the present invention suppressed AR expression, and thus it was confirmed to have an anti-androgenic effect.

[0087] In hair loss induction, premature termination of follicle growth due to apoptosis is known as one of the important factors. Therefore, the expression of mRNAs of Bcl-2, Bax and caspase-9 in skin tissues was confirmed, and the results are shown in FIG. 7. Cs-EE according to the present invention increased the expression level of Bcl-2 mRNA (see FIG. 7a), whereas the expression of mRNAs of Bax and caspase-9, which are genes having pro-apoptotic properties, was significantly decreased (see FIGS. 7b and 7c).

[0088] Also, as shown in FIG. 8, it was confirmed that the expression of cleaved caspase-3 increased by testosterone was decreased by treatment with Cs-EE according to the present invention. It was also confirmed that the expression of Bcl-2 decreased by testosterone was restored by treatment with Cs-EE according to the present invention. Therefore, it was confirmed that the hair protection and growth promoting effects of Cs-EE according to the present invention are derived from the downregulation of the AR and apoptosis pathways by this means.

[0089] Example 5. Confirmation of the effect of Cs-EE on the proliferation and survival of HDP cells The effect of Cs-EE according to the present invention on the growth of HDP cells was confirmed. As a result, as shown in FIG. 9a, it was confirmed that the growth of HDP increased due to the presence of Cs-EE according to the present invention. Also, as shown in FIG. 9b, 100 nM of DHT showed cytotoxicity against HDP cells, and co-treatment with Cs-EE according to the present invention restored the growth of HDP cells by up to 100%. Thereby, it was confirmed that Cs-EE according to the present invention can block the androgen pathway and prevent the death of HDP cells.

[0090] In addition, the cytotoxicity of Cs-EE according to the present invention against HDP cells was confirmed. As a result, as shown in FIG. 9c, Cs-EE according to the present invention not only did not affect the viability of cells even at a concentration of 100 μg / ml, but rather greatly increased cell viability in treatments at concentrations of 100 μg / ml or higher.

[0091] Example 6. Confirmation of the effect of Cs-EE on 5-α reductase and anti-apoptosis process in HDP cells Through the activation analysis of 5-α reductase, the mechanism of the anti-androgen activity of Cs-EE according to the present invention was confirmed. As a result, as shown in FIG. 10, when treated with 100 μg / ml or more of Cs-EE, the activity of 5-α reductase was decreased to less than 40%. Therefore, it was confirmed that the effect of decreasing the level of AR protein of Cs-EE according to the present invention confirmed above was induced from the effect of suppressing the activity of 5-α reductase of Cs-EE.

[0092] In addition, in order to confirm the hair loss prevention effect of Cs-EE in vitro, after treating with Cs-EE and then treating HDP cells with 100 nM of DHT, the change in the expression of gene mRNA was confirmed.

[0093] As a result, as shown in FIG. 11a, Cs-EE of the present invention increased the expression of mRNA of Bcl-2, which had been decreased by DHT in a dose-dependent manner. On the one hand, as shown in Fig. 11b, the Cs-EE of the present invention significantly decreased the expression of caspase-9 mRNA, a gene having pre-apoptotic characteristics. Overall, the present invention relates to a Connarus semidecandrus Jack. extract having a hair removal treatment effect. According to the present invention, when the Connarus semidecandrus Jack. extract is treated in a testosterone-mediated alopecia animal model, hair growth is promoted, the length and thickness of the hair are also increased, the expression of androgen receptor and apoptosis-related factors is suppressed, the survival and proliferation of human dermal papilla cells are promoted, and the activity of 5-α reductase is suppressed. That is, the Connarus semidecandrus Jack. extract according to the present invention can be usefully utilized in various applications for hair loss prevention or treatment, hair growth or hair growth promotion.

Claims

1. A pharmaceutical composition for preventing or treating hair loss, comprising an extract of Connarus semidecandrus Jack.

2. The pharmaceutical composition according to claim 1, wherein the extract is extracted with any one solvent selected from the group consisting of water, C1 to C4 alcohols, and mixed solvents thereof.

3. The pharmaceutical composition according to claim 1, wherein the extract is extracted from any one or more parts selected from the group consisting of the whole plant, aerial part, root, leaf, seed, and flower of Connarus semidecandrus Jack.

4. The pharmaceutical composition according to claim 1, wherein the hair loss is one or more selected from the group consisting of male pattern hair loss, female pattern hair loss, alopecia areata, and telogen effluvium.

5. A quasi-drug composition for preventing or improving hair loss, comprising an extract of Connarus semidecandrus Jack.

6. A cosmetic composition for preventing or improving hair loss, comprising an extract of Connarus semidecandrus Jack.

7. A food composition for preventing or improving hair loss, comprising an extract of Connarus semidecandrus Jack.

8. A health functional food composition for preventing or improving hair loss, comprising an extract of Connarus semidecandrus Jack.

9. A pharmaceutical composition for promoting hair growth or hair regrowth, comprising an extract of Connarus semidecandrus Jack.

10. A quasi-drug composition for promoting hair growth or hair regrowth, comprising an extract of Connarus semidecandrus Jack.

11. A cosmetic composition for promoting hair growth or hair regrowth, comprising an extract of Connarus semidecandrus Jack.

12. A food composition for promoting hair growth or hair regrowth, comprising an extract of Connarus semidecandrus Jack.

13. A health functional food composition for promoting hair growth or hair growth containing an extract of Connarus semidecandrus Jack.

14. A method for treating hair loss, comprising the step of treating an individual with an extract of Connarus semidecandrus Jack.

15. A method for promoting hair growth or hair growth, comprising the step of treating an individual with an extract of Connarus semidecandrus Jack.

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