5α-reductase inhibitors

Abstract

To provide 5α-reductase inhibitors containing a novel substance as the effective ingredient.SOLUTION: 1. A 5α-reductase inhibitor containing an extract of Aguaje (Mauritia flexuosa) as an effective ingredient. 2. The 5α-reductase inhibitor of 1. where the extract contains a methoxyflavan compound. 3. A 5α-reductase inhibitor containing a methoxyflavan compound as an effective ingredient. 4. The 5α-reductase inhibitor of 2. or 3, where the methoxyflavan compound is at least one of 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, 6,7,4'-hydroxy-5-methoxyflavan and 7,8,4'-hydroxy-5-methoxyflavan. 5. The 5α-reductase inhibitor of 3, where the methoxyflavan compound is derived from Aguaje.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a novel 5α-reductase inhibitor, which can be widely used in foods, medicines, cosmetics, etc. [Background technology]

[0002] The prostate is an organ located just below the bladder in men and surrounding the posterior urethra. It is believed that prostate enlargement is caused by the accumulation of dihydrotestosterone (DHT). DHT is produced by the conversion of testosterone by 5α-reductase. When testosterone is taken up into prostate cells, it is converted to DHT by the 5α-reductase present in the prostate cells, and DHT promotes cell proliferation. As a result, the prostate enlarges (benign prostatic hyperplasia) and causes urinary problems. Therefore, inhibiting 5α-reductase, which is an enzyme that synthesizes DHT (active form) in cell proliferation, is significant in terms of suppressing dysuria associated with prostatic hyperplasia (Patent Document 1 and Non-Patent Documents 1 to 3).

[0003] In addition, testosterone biosynthesized in the testes etc. is converted to dihydrotestosterone by 5α-reductase present in hair follicles, sebaceous glands etc. in the head. This dihydrotestosterone significantly reduces the activity of adenyl cyclase, leading to a decrease in intracellular cyclic AMP levels, which is thought to result in a decrease in energy production in and around the hair and inhibition of protein synthesis, thereby progressing male pattern baldness (Patent Document 2).

[0004] Recently, there has been a trend to focus on the properties of substances, such as 5α-reductase inhibitory activity, hair matrix cell activation activity, and blood circulation promotion activity, and to use these substances as hair nourishment and hair growth agents.

[0005] Furthermore, in recent years, the desire to remain beautiful, healthy and youthful has become stronger among people of all ages and genders. Therefore, in the age group of 11 to 25 years old, acne is something that should not be forgotten from the perspective of beautiful skin. Acne is officially called acne vulgaris. 70-80% of patients are concentrated in the age group of 11-25 years old, and mild acne can be said to be one of the characteristics of adolescent skin rather than a skin disease. However, severe acne is unsightly and often leaves scars even after healing. In some people, the mere presence of acne can make them feel depressed, and it often affects their daily life and social activities. Therefore, from a cosmetic standpoint, it is necessary to take appropriate measures as soon as possible to restore normal, beautiful skin.

[0006] In addition, dihydrotestosterone, which is produced from testosterone by 5α-reductase, is thought to be involved in the occurrence and aggravation of acne. If the production of dihydrotestosterone can be suppressed or inhibited by a drug with 5α-reductase inhibitory activity, the occurrence and aggravation of acne can be suppressed (Patent Document 3).

[0007] [Non-Patent Document 1] Supervisor: Goto Hyomamo; Editor: Medical Information Science Institute, Visible Medicine, 1, Published by Medic Media, P436-438 (2014). [Non-Patent Document 2] Jie L., et. al., Biol. Pharm. Bull., 29 (2), P392-395 (2006). [Non-Patent Document 3] Koseki J., et al., Evidence-Based Complementary and Alternative Medicine, Article ID 853846 (2015). [Patent Document 1] JP 2011-00972 A [Patent Document 2] Japanese Patent Application Publication No. 05-097684 [Patent Document 3] JP 2007-099751 A Summary of the Invention [Problem to be solved by the invention]

[0008] Under these circumstances, the present inventors discovered that aguaje extract and the methoxyflavan compounds contained therein have 5α-reductase inhibitory activity, and thus completed the present invention. The present invention has an object to solve the above problems, and to provide a novel 5α-reductase inhibitor. [Means for solving the problem]

[0009] The features of the present invention for solving the above problems are as follows. 1. A 5α-reductase inhibitor whose active ingredient is aguaje extract. 2. The 5α-reductase inhibitor described in 1 above, wherein the aguaje extract contains a methoxyflavan compound. 3. A 5α-reductase inhibitor whose active ingredient is a methoxyflavan compound. 4. The above methoxyflavan compounds are 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, and 6,7,4'- tri hydroxy-5-methoxyflavan, 7,8,4' -tri 5. A 5α-reductase inhibitor according to claim 2 or 3, which is at least one of hydroxy-5-methoxyflavan. 5. The 5α-reductase inhibitor described in 3 above, characterized in that the methoxyflavan compound is derived from aguaje. 6. A prostate-specific antigen (PSA) gene expression inhibitor containing aguaje extract as an active ingredient. 7. A prostate-specific antigen (PSA) protein expression inhibitor containing a methoxyflavan compound as an active ingredient. 8. The prostate-specific antigen (PSA) protein expression inhibitor according to 7. above, wherein the methoxyflavan compound is 7,8,4'-trihydroxy 5-methoxyflavan. 9. A prostate-specific antigen (PSA) gene expression inhibitor containing a methoxyflavan compound as an active ingredient. 10. The prostate-specific antigen (PSA) gene expression inhibitor according to claim 9, wherein the methoxyflavan compound is at least one of 4'-hydroxy 5,7-dimethoxyflavan, 7,4'-dihydroxy 5-methoxyflavan and 6,7,4'-trihydroxy 5-methoxyflavan. 11. A prostate-specific antigen (PSA) protein expression inhibitor containing aguaje extract as the active ingredient. 12. A prostatic hyperplasia inhibitor comprising any one of the agents described in 1. to 11. above as an active ingredient. 13. An agent for suppressing male pattern baldness, comprising as an active ingredient a 5α-reductase inhibitor according to any one of 1. to 5. above. 14. An acne prevention and improvement agent comprising as an active ingredient a 5α-reductase inhibitor as described in any one of 1. to 5. above. Effect of the Invention

[0010] According to the present invention, by using aguaje extract as an active ingredient, it is possible to provide more excellent 5α-reductase inhibition. Furthermore, according to the present invention, by including a methoxyflavan compound in the aguaje extract, it is possible to provide excellent 5α-reductase inhibition, and by using the methoxyflavan compound itself as an active ingredient, it is possible to provide even more excellent 5α-reductase inhibition. Furthermore, among the methoxyflavan compounds, 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, and 6,7,4'- tri hydroxy-5-methoxyflavan, 7,8,4'-tri Hydroxy-5-methoxyflavan has excellent 5α-reductase inhibitory activity, and therefore, by using these, it is possible to provide an even more excellent 5α-reductase inhibitor. In addition, the present invention has an excellent 5α-reductase inhibitory effect, and therefore inhibits the conversion of testosterone to DHT by 5α-reductase, thereby suppressing the proliferation of prostate cells caused by DHT, thereby providing an excellent prostate hyperplasia inhibitory effect. Furthermore, the present invention has an excellent 5α-reductase inhibitory effect, and therefore testosterone inhibits the production of dihydrotestosterone by 5α-reductase present in hair follicles, sebaceous glands, etc. on the head. This reduces the activity of adenyl cyclase and inhibits the decrease in intracellular cyclic AMP level, thereby inhibiting the decrease in energy production in and around the hair and inducing protein synthesis, thereby inhibiting the progression of male pattern baldness, and thus providing an excellent male pattern baldness inhibitor. In addition, because it has a 5α-reductase inhibitory effect, it suppresses the production of dihydrotestosterone, thereby suppressing the occurrence and aggravation of acne. [Brief description of the drawings]

[0011]

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Mode for Carrying Out the Invention

[0012] Hereinafter, the present invention will be described in detail. The present invention is characterized by using an Aguaje extract as an active ingredient. Aguaje is a palm plant native to South America, with the scientific name Mauritia flexuosa L.f., and is also known as Militzia ice, Aguajares, Omitegu Yashi (Japanese), and Miriti palm (English).

[0013] In the present invention, when extracting the active ingredient from Aguaje, the part is not particularly limited. For example, fruits, seeds, flowers, leaves, roots, stems, etc. can be used, and it is particularly preferable to use fruits. This is because the active ingredient can be extracted at a high concentration. At this time, as a preferable solvent, those mainly composed of non-polar solvents such as n-hexane, acetone, and ethyl acetate are preferable. This is because the use of non-polar solvents can remove the contamination of polysaccharides contained in Aguaje. In particular, it is preferable to use n-hexane as the non-polar solvent. This is because it makes it easier to use the extract for food materials, etc. Incidentally, only one of these degreasing solvents may be used, or two or more may be used in combination. In addition, in order to improve the extraction efficiency of the active ingredient, it is preferable to use a solvent that contains a polar solvent as a part of the non-polar solvent as the main component. This is because it is difficult to extract the active ingredient at a sufficient concentration when only a non-polar solvent is used. Here, the polar solvent is not particularly limited, but examples thereof include water, lower monohydric alcohols (methyl alcohol, ethyl alcohol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1,3-butylene glycol, etc.), lower esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile, etc., and one or more of them can be used. The most preferred combination is a mixture of hexane and ethanol, because it is highly safe and can be used to extract food materials.

[0014] When a mixture of hexane and ethanol is used as the extraction solvent, the ratio is not particularly limited, but the mixture ratio of hexane / ethanol can be 60 / 40 to 99 / 1, or even 70 / 30 to 99 / 1, because it is possible to extract a higher concentration of the active ingredient.

[0015] It is also preferable to use dried and crushed aguaje fruit as the aguaje fruit. In the case of raw fruit, the extraction method may be, for example, a method in which the aguaje fruit is pressed and then the oil is separated using the above-mentioned solvent, or the oil may be separated by pressing and then the residual oil in the pressed product may be extracted and separated using the above-mentioned solvent (fat-soluble organic solvent).

[0016] The extraction temperature is preferably about 20 to 50° C., and more preferably about 30 to 40° C. If the extraction temperature is too low, the active ingredient is difficult to extract, and if the extraction temperature is too high, the active ingredient deteriorates.

[0017] As the extraction method, any method such as stirring extraction, continuous extraction, immersion extraction, countercurrent extraction, and supercritical extraction can be adopted, and any apparatus can be used at room temperature or under reflux heating.

[0018] The specific extraction method is as follows: roughly crushed raw material (e.g. powdered aguaje fruit) is placed in a processing tank, which is then filled with an extraction solvent and stirred to dissolve the active ingredients. For example, when using hexane and ethanol as the extraction solvent, about 5 to 20 times the amount (by weight) of the extraction solvent is used as the raw material, and extraction is carried out for about 30 minutes to 2 hours. After the active ingredients are dissolved in the solvent, the extract is obtained by filtering to remove the extraction residue. The aguaje extract preferably contains methoxyflavan compounds. In addition, methoxyflavan refers to a compound represented by the following chemical formula (1). [ka] Here, R1 to R3 are The substituents shown in Table 1 described below It is.

[0019] The methoxyflavan compound is not particularly limited, but examples thereof include 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, and 6,7,4' -tri hydroxy-5-methoxyflavan, 7,8,4'- tri Hydroxy-5-methoxyflavan and the like are preferred. Incidentally, only one of these may be contained, or two or more may be contained. Incidentally, the chemical formulas of these compounds are those shown in the following Table 1 in the above chemical formula (1).

[0020] [Table 1]

[0021] The present invention is also characterized in that the above methoxyflavan compound is used as an active ingredient. Further, the above methoxyflavan compounds include 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, and 6,7,4'- tri hydroxy-5-methoxyflavan, 7,8,4'- tri Hydroxy-5-methoxyflavan and the like are preferred. In addition, the above methoxyflavan compounds, 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, and 6,7,4'- tri hydroxy-5-methoxyflavan, 7,8,4'- tri The chemical formula of hydroxy-5-methoxyflavan is shown in the above chemical formula (1) and Table 1. These may be used alone or in combination of two or more kinds.

[0022] The method for obtaining the methoxyflavan compound is not particularly limited, but it can be obtained by separating it from the aguaje extract. In addition, the method for separating the methoxyflavan compounds from the aguaje extract is not particularly limited, but they can be obtained by dissolving the aguaje extract in water and ethyl acetate, then partitioning the ethyl acetate layer, and then purifying this ethyl acetate fraction.

[0023] The method for purifying the ethyl acetate fraction is not particularly limited, but it is preferable to pass the extract through a synthetic adsorption resin, gel filtration resin, etc. to adsorb the active ingredient, and then to concentrate it by eluting it with methanol, ethanol, etc. Specific examples include silica gel column chromatography and high performance liquid chromatography, and more specifically, the methoxyflavan compound can be obtained by the method described in the Examples of this specification.

[0024] The 5α-reductase inhibitor of the present invention can be used as an ingredient in various foods and beverages. Examples of foods and beverages include general foods such as edible oils (salad oils, confectioneries (gum, candy, caramel, chocolate, cookies, snacks, jellies, gummies, tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, green tea, carbonated drinks, sports drinks, etc.), health foods (tablets, capsules, etc.), and nutritional supplements (nutritional drinks, etc.). The 5α-reductase inhibitor of the present invention may be appropriately blended into these foods and beverages.

[0025] These foods and beverages can contain various ingredients depending on their type, such as food ingredients such as glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorants, flavorings, and preservatives. In addition, this 5α-reductase inhibitor with health maintenance function contains other antioxidants and health food ingredients, such as reduced ascorbic acid (vitamin C), vitamin E, reduced glutathione, tocotrienol, vitamin A derivatives, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignans, catechin, isoflavones, chalcone, tannins, flavonoids, coumarin, isocoumarins, blueberry extract, health food ingredients) V. (vitamin) A, V.B1, V.B2, V.B6, V.B12, VC, VD, VE, VP, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharides, dietary fiber, sucrose, glycerin, niacin, glycerin, glycerol ... Allen, soy lecithin, taurine, dunaliella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, elastin, turmeric, licorice, wolfberry, cinnamon bark, hawthorn, ginger, reishi, clam extract, soft-shelled turtle, licorice, wolfberry, cinnamon bark, hawthorn, ginger, reishi, plantain, chamomile, chamomile, dandelion, hibiscus, honey, bolen, royal jelly, lime, lavender, rosehip, rosemary, sage, bifidobacteria, faecalis bacteria, lacrys, wheat germ oil, sesame oil, perilla oil, soybean oil, medium chain fatty acids, agaricus, ginkgo leaf extract,Chondroitin, brown rice germ extract, lychee, onion, DHA, EPA, DPA, sweet tea, cordyceps, garlic, bee larvae, papaya, pu-erh, propolis, megusuri tree, yarrow, royal jelly, saw palmetto, longevity grass, black ginger, seaberry, pumpkin, hyaluronic acid, GABA, harp seal oil, shark cartilage, glucosamine, lecithin, phosphatidylserine, ginseng, mulberry leaves, soybean extract, echinacea, Ezo Aralia, barley extract, olive leaf, olive fruit, gymnema, banaba, salacia, garcinia, chitosan, St. John's wort, jujube, carrot, passion flower, broccoli, placenta, pearl barley, grape seed, peanut husk, bilberry, black cohosh, milk thistle, bay laurel, sage, rosemary, rafuma, black vinegar, bitter melon, maca, safflower, flax, oolong tea, thorns, caffeine, capsaicin, xylophilus Sugar, glucosamine, buckwheat, citrus, dietary fiber, protein, prunes, spirulina, young barley leaves, nucleic acid, yeast, shiitake mushrooms, plum flesh, amino acids, deep-sea shark extract, noni, oyster meat, soft-shelled turtle, champignon, plantain, acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, pheshimakobu, cranberry, zinc, iron, silk peptide, glycine, niacin, chaste tree, ceramide, L- Cysteine, red wine juice, millet, horsetail, biotin, Centella asiatica, haskap, pycnogenol, butterbur, rhubarb, clove, pu-erh, citric acid, brewer's yeast, melilot, black ginger, ginger, zedoary, nattokinase, monascus, tocotrienol, lactoferrin, tartary buckwheat, cocoa, dokudami, kiwi, long pepper, lotus leaf, pfaffia, star fruit, etc. can also be added.

[0026] A specific manufacturing method involves spray-drying or freeze-drying the aguaje extract or methoxyflavan compounds together with powdered cellulose, and then turning this into a powder, granules, tablets, or solution, which can be easily incorporated into food and beverages (such as instant foods). The aguaje extract may be dissolved in, for example, fats and oils, ethanol, glycerin, or a mixture thereof to form a liquid, which may then be added to beverages or solid foods. If necessary, the aguaje extract may be mixed with a binder such as gum arabic or dextrin to form a powder or granules, which may then be added to beverages or solid foods.

[0027] When the 5α-reductase inhibitor of the present invention is applied to food and beverages, the amount of active ingredient added is preferably 1 to 20 wt % in total, since the main purpose is disease prevention and health maintenance.

[0028] The 5α-reductase inhibitor of the present invention may be used as a material for drugs (including pharmaceuticals and quasi-drugs). Drugs can be produced by appropriately mixing the 5α-reductase inhibitor of the present invention with raw materials for pharmaceutical formulations. Examples of raw materials for formulations that can be mixed with the 5α-reductase inhibitor of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hardened vegetable oil, kaolin, talc, etc.), binders (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, agar, Examples of suitable additives include sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearate monoglyceride, starch, lactose, powdered acacia, gelatin, ethanol, etc.), disintegration inhibitors (white sugar, stearin, cacao butter, hydrogenated oil, etc.), absorption enhancers (quaternary ammonium bases, sodium lauryl sulfate, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, etc.).

[0029] The 5α-reductase inhibitor according to the present invention can be administered orally in the form of tablets, pills, soft or hard capsules, fine granules, powders, granules, liquids, etc., but may also be administered parenterally. When administered parenterally, it can be applied in the form of a solution or with the addition of a dispersing agent, suspending agent, stabilizer, etc., in the form of a poultice, lotion, ointment, tincture, cream, etc.

[0030] The dosage may vary depending on the method of administration, the condition, the age of the patient, etc., but typically, for adults, 1 to 1000 mg of the active ingredient can be administered per day, and for children, 0.5 to 500 mg. The compounding ratio of the 5α-reductase inhibitor can be appropriately changed depending on the dosage form, but it is usually about 0.3 to 15.0 wt % when administered orally or via mucosal absorption, and about 0.01 to 10 wt % when administered parenterally. Note that the dosage varies depending on various conditions, so in some cases a smaller dosage than the above-mentioned dosage is sufficient, and in other cases it is necessary to administer it beyond the range.

[0031] Examples of the forms of topical skin preparations that can be formulated with the 5α-reductase inhibitors of the present invention include lotions, soaps, facial cleansers, bath additives, creams, lotions, skin toners, colognes, shaving creams, shaving lotions, cosmetic oils, suntan / sunscreen lotions, face powders, foundations, perfumes, packs, nail creams, enamel, enamel removers, eyebrow ink, blushers, eye creams, eye shadows, mascara, eyeliners, lipsticks, lip balms, shampoos, rinses, treatments, hair dyes, dispersions, cleansers, and the like. Furthermore, examples of the forms of pharmaceuticals or quasi-drugs that can contain the 5α-reductase inhibitor of the present invention include ointments, creams, and liquids for external use.

[0032] In addition to the 5α-reductase inhibitor of the present invention, the above-mentioned topical skin preparations can contain ingredients that are incorporated into topical skin preparations such as cosmetics and quasi-drugs, as long as the 5α-reductase inhibitory effect is not impaired, such as oils, higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols, sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, etc. Examples are listed below, but the present invention is not limited to these examples. (1) Example of oil Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, diisopropyl adipate isopropyl, isoarachyl neopentanoate, tri(caprylic / capric)glyceryl, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearate Tearyl, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol dicaprylate, propylene glycol dicaprylate, dicaprin Neopentyl glycol acid, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleate, polyglycerin isostearate, dipropyl carbonate,Dialkyl carbonate (C12-18), triisocetyl citrate, triisoarachyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate propyl, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoylhydroxystearate, stearyl 12-stearoylhydroxystearate, isostearyl 12-stearoylhydroxystearate, and the like. Hydrocarbon-based oil phase component Examples of suitable waxes include squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, and petrolatum. Animal and vegetable oils and their hydrogenated oils, and waxes of natural origin: beef tallow, hydrogenated beef tallow, lard, hydrogenated lard, horse oil, hydrogenated horse oil, mink oil, orange roughy oil, fish oil, hydrogenated fish oil, egg yolk oil, and other animal oils and their hydrogenated oils, avocado oil, almond oil, olive oil, cocoa butter, apricot kernel oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, hydrogenated rapeseed oil Examples of such vegetable oils include oleaginous oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil, sunflower oil, grape seed oil, jojoba oil, hydrogenated jojoba oil, macadamia nut oil, medicamentoil, cottonseed oil, hydrogenated cottonseed oil, coconut oil, and hydrogenated coconut oil, as well as their hydrogenated oils, beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax, montan wax, and other waxes. Silicone-based oil phase componentExamples of suitable organic solvents include dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic silicone, trimethylsiloxysilicate, and silicone RTV rubber. Fluorine-based oil phase components: Perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl-polyoxyalkylene-co-modified organopolysiloxane, etc. (2) Examples of higher alcohols Examples of the alcohol include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, and octyldodecanol. (3) Examples of fatty acids Examples of the acid include caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, erucic acid, and 2-ethylhexanoic acid. (4) Examples of UV absorbers Para-aminobenzoic acid, amyl para-aminobenzoate, dihydroxypropyl ethyl para-aminobenzoate, glyceryl para-aminobenzoate, ethyl para-aminobenzoate, octyl para-aminobenzoate, dimethyl octyl para-aminobenzoate, ethylene glycol salicylate, octyl salicylate, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl para-methoxycinnamate, 2-ethylhexyl para-methoxycinnamate, glyceryl di-para-methoxycinnamate mono 2-ethylhexanoate, isopropyl para-methoxycinnamate, diethanolamine salt of para-methoxyhydrocinnamate, mixture of diisopropyl and diisopropyl cinnamate, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, di Hydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butylmethoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2-ethylhexyl-1-oxy)-1,3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenylacrylate, phenylbenzimidazole sulfate, 3-(4-methylbenzylidene)camphor, isopropyldibenzoylmethane, 4-(3,4-dimethoxyphenylmethylene)-2,5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like, as well as polymer derivatives and silane derivatives thereof. (5) Examples of powders and pigments Dyes such as Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401, lake dyes such as Yellow No. 4 AL Lake, Yellow No. 203 BA Lake, nylon powder, silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder and other polymers, yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, carbon black, ultramarine, Prussian blue and other colored pigments, zinc oxide, titanium oxide, acid Examples of such pigments include white pigments such as cerium chloride, extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate, pearl pigments such as titanium mica, metal salts such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, and magnesium silicate, inorganic powders such as silica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, and zinc undecylenate, bentonite, smectite, and boron nitride. There are no particular limitations on the shape (spherical, rod-like, needle-like, plate-like, irregular, flaky, spindle-like, etc.) and particle size of these powders. These powders may or may not have been previously surface-treated by a conventionally known surface treatment, such as a fluorine compound treatment, a silicone treatment, a silicone resin treatment, a pendant treatment, a silane coupling agent treatment, a titanium coupling agent treatment, an oil treatment, an N-acylated lysine treatment, a polyacrylic acid treatment, a metal soap treatment, an amino acid treatment, a lecithin treatment, an inorganic compound treatment, a plasma treatment, or a mechanochemical treatment. (6) Examples of surfactants Anionic surfactant Examples of the suitable surfactants include fatty acid soaps, α-acylsulfonates, alkylsulfonates, alkylarylsulfonates, alkylnaphthalenesulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkyloylalkyl taurine salts, N-acylamino acid salts, POE alkyl ether carboxylates, alkylsulfosuccinates, sodium alkylsulfoacetates, acylated hydrolyzed collagen peptide salts, and perfluoroalkyl phosphate esters. Cationic surfactant Examples of the surfactants include alkyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, behenyl trimethyl ammonium bromide, benzalkonium chloride, behenic acid amidopropyl dimethyl hydroxypropyl ammonium chloride, stearate diethylaminoethylamide, stearate dimethylaminopropylamide, and lanolin derivative quaternary ammonium salts. Amphoteric surfactant Examples of the betaine type include carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imitazoline derivative type, and amidoamine type. Nonionic surfactant : Propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE·POP copolymer, POE·POP alkyl ether, polyether modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, etc. Natural surfactant Examples include lecithin, saponin, sugar-based surfactants, etc. (7) Examples of polyhydric alcohols and sugars Examples of suitable sugars include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3-butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan, etc. Chemically modified versions of these sugars may also be used. (8) Examples of polymers Acrylic acid ester / methacrylic acid ester copolymer (Plussize, manufactured by GOO Chemical Co., Ltd.), vinyl acetate / crotonic acid copolymer (Resin 28-1310, manufactured by NSC Co., Ltd.), vinyl acetate / crotonic acid / vinyl neodecanoate copolymer (28-2930, manufactured by NSC Co., Ltd.), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP Co., Ltd.), t-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (Rubymer, manufactured by BASF Co., Ltd.), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Ruviscol VAP, manufactured by BASF), vinyl acetate / crotonic acid copolymer (Rubyset CA, manufactured by BASF), vinyl acetate / crotonic acid / vinyl pyrrolidone copolymer (Rubyset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubyflex, manufactured by BASF), acrylate / acrylamide copolymer (Ultrahold, manufactured by BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, manufactured by ISP), carboxyvinyl polymer (Carbopol, BFGoo anionic polymer compounds such as acrylic acid / alkyl methacrylate copolymer (Pemulen, BFGoodrich); amphoteric polymer compounds such as dialkylaminoethyl methacrylate polymer acetate amphoteric compound (Yukaformer, Mitsubishi Chemical); acrylic acid octyl acrylamide / hydroxypropyl acrylate / butylaminoethyl methacrylate copolymer (AMPHOMER, NSC); vinylpyrrolidone / dimethylaminoethyl methacrylate quaternary compound (GAFQUAT, ISP); Examples of such polymer compounds include cationic polymer compounds such as lumidazolium chloride / vinylpyrrolidone copolymer (Rubicort, manufactured by BASF), and nonionic polymer compounds such as polyvinylpyrrolidone (Ruviscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (Ruviscol VA, manufactured by BASF), vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer 937, manufactured by ISP), and vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer VC713, manufactured by ISP).Also suitable for use are naturally occurring polymeric compounds such as cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabinogalactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum, and dextran. (9) Examples of physiologically active ingredients Examples of the physiologically active ingredient include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening ingredients, anti-inflammatory agents, anti-aging agents, UV protection agents, slimming agents, tightening agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, drying agents, cooling agents, warming agents, vitamins, amino acids, wound healing promoters, irritation relievers, analgesics, cell activators, enzyme ingredients, etc. Examples of suitable ingredients include angelica extract, avocado extract, amacha extract, althea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo extract, fennel extract, turmeric extract, oolong tea extract, eijitsu extract, echinacea leaf extract, scutellaria extract, phellodendron bark extract, coptis extract, barley extract, hypericum extract, white nettle extract, watercress extract, orange extract, seawater, etc. Dried products, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, carrot extract, artemisia capillaris extract, licorice extract, kalk extract, kakyoku extract, kiwi extract, cinchona extract, cucumber extract, guanosine, gardenia extract, kumazasa extract, sophora flavescens extract, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentiana extract, black tea extract, yeast extract, burdock Kiss, fermented rice bran extract, rice germ oil, comfrey extract, collagen, lingonberry extract, saishin extract, saiko extract, umbilical cord extract, salvia extract, soapwort extract, bamboo extract, hawthorn extract, Japanese pepper extract, shiitake mushroom extract, rehmannia extract, lithospermum extract, perilla extract, linden extract, meadowsweet extract, peony extract, calamus root extract, white birch extract, horsetail extract, ivy extract, hawthorn extract , Elderberry extract, Yarrow extract, Peppermint extract, Sage extract, Mallow extract, Cnidium officinalis extract, Swertia japonica extract, Soybean extract, Chinese laurel extract, Thyme extract, Tea extract, Clove extract, Imperata cylindrica extract, Citrus aurantium extract, Angelica acutiloba extract, Calendula officinalis extract, Peach kernel extract, Spruce extract, Houttuynia cordata extract, Tomato extract, Natto extract, Carrot extract, Garlic extract, Wild rose extract, Hibiscus extract,Examples of such extracts include burdock root extract, parsley extract, honey, witch hazel extract, parietaria extract, burdock root extract, bisabolol, loquat extract, coltsfoot extract, butterbur bud extract, poria extract, butcher's broom extract, grape extract, propolis, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, melissa extract, peach extract, cornflower extract, eucalyptus extract, saxifrage extract, coix seed extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, strawberry extract, long pepper extract, lotus leaf extract, paffia extract, and star fruit extract. In addition, it contains biopolymers such as deoxyribonucleic acid, mucopolysaccharides, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, and hydrolyzed eggshell membrane, moisturizing ingredients such as amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidone carboxylate, betaine, whey, and trimethylglycine, oily ingredients such as sphingolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, and phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, and guaiazure. anti-inflammatory agents such as vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoids, flavonoids, tannins, lignans, saponins, cell activators such as α-hydroxy acids, β-hydroxy acids, blood circulation promoters such as γ-oryzanol, vitamin E derivatives, Wound healing agents such as tinol and retinol derivatives, skin whitening agents such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, and glutathione, cepharanthine, licorice extract, capsicum tincture, hinokitiol, iodized garlic extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives, calcium pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropyl methylphenol, estradiol ethanol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, vanillylamide nonylate, vanillylamide nonanoate, piroctone olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol, gamma-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormones, cantharides tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil,Examples include hair growth agents such as Sasanishiki extract. (10) Examples of antioxidants Examples of such antioxidants include sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxytoluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponin, and plant extracts such as apple extract and clove extract that are recognized to have antioxidant effects. (11) Examples of solvents Examples of suitable solvents include purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile straight-chain silicones, and next-generation fluorocarbons. EXAMPLES

[0033] Hereinafter, an embodiment of the present invention will be described. Example 1: Preparation of Aguaje Extract Hexane (2 L) was added to the dried powder of Peruvian aguaje fruit (2 kg) and the mixture was stirred (40°C, 1 hour). After filtration, hexane was added to the residue, and the above defatted procedure was repeated two more times. Ethanol (3 L) was added to the defatted residue and extraction was performed (60°C, 1 hour). The filtrate was concentrated and dried to obtain an ethanol extract (124 g) (Example 1). Example 2: Isolation of methoxyflavan compounds from the aguaje extract The above aguaje extract was subjected to silica gel column chromatography, and eluted with hexane → hexane:ethyl acetate (5:1) → hexane:ethyl acetate (2:1) → hexane:ethyl acetate (1:1) → ethyl acetate → methanol in that order. The solvent was distilled off to obtain a hexane:ethyl acetate (2:1) fraction (260 mg), a hexane:ethyl acetate (1:1) fraction (260 mg), an ethyl acetate fraction (770 mg), and a methanol fraction (1.5 g). The ethyl acetate fraction (700 mg) was repeatedly purified by HPLC (column: Capcelpack C18 20×250 mm, Osaka Soda, solvent: methanol:acetone:water (3:3:4), detection: differential refractometry) to obtain 7,8,4' -tri The hexane:ethyl acetate (1:1) fraction (200 mg) was repeatedly purified by HPLC (column: Capcelpack C18 20×250 mm, Osaka Soda, solvent: methanol:acetone:water (3:3:4), detection: differential refractive index) to give 7,4'-dihydroxy-5-methoxyflavan (0.9 mg), 4'-hydroxy-5,7-dimethoxyflavan (10 mg), and 6,7,4'- tri Hydroxy-5-methoxyflavan (9.2 mg) was obtained.

[0034] Test example: Evaluation of 5α-reductase inhibition Test Method The evaluation was carried out as follows. 20 mM potassium phosphate buffer (pH 6.5) containing 1 mM dithiothreitol, 3.5 mM testosterone, DMSO solution containing the test substance, 100 μM nicotinamide adenin dinucleotide phosphate (NADPH), and 20 μg protein of female rat liver microsomes were added to a 48-well plate to a final volume of 500 μL / well. DMSO was used instead of the test substance as a comparison of activity. The reaction solution excluding the microsomes was incubated at 37°C for 10 minutes, and then the microsome solution was added and incubated at 37°C for 30 minutes. Then, 5M sodium hydroxide solution was added to stop the enzyme reaction. 450 μL of the reaction solution was transferred to a microtube, and then ethyl acetate was added for partition extraction. Testosterone migrates to the ethyl acetate layer, so the ethyl acetate layer was transferred to a new microtube and dried under a nitrogen stream. Then, 30 μL of 60% methanol solution containing the internal standard dexamethasone (20 μg / mL) was added to dissolve the substrate testosterone.Then, the testosterone concentration was calculated from the testosterone / dexamethasone peak area ratio in the solution using HPLC and the internal standard method.

[0035] Test Example 1: Aguaje Extract Using the above method, we first evaluated the 5α-reductase inhibitory effect of the aguaje extract alone. The results are shown in Table 1 and Figure 1.

[0036] [Table 2]

[0037] Results and Effects of the Examples in Test Example 1 As shown in Table 2, the 5α-reductase inhibitory activity of the aguaje extract was evaluated, and it was found that the extract inhibited 5α-reductase in a concentration-dependent manner, confirming that the aguaje extract is useful as a 5α-reductase inhibitor.

[0038] Test Example 2: Regarding Methoxyflavan Compounds By the above method, the 5α-reductase inhibitory effects of methoxyflavan compounds (4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, 6,7,4'- tri hydroxy-5-methoxyflavan, 7,8,4'- tri hydroxy-5-methoxyflavan) isolated from the Aguahe extract were evaluated. The results are shown in Table 2 below.

[0039]

Table 3

[0040] Results and Effects of the Examples in Test Example 2 As shown in Table 3, for the methoxyflavan compounds (4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, 6,7,4'-trihydroxy-5-methoxyflavan, 7,8,4'-tirhydroxy-5-methoxyflavan) isolated from Aguahe, inhibitory activity was observed in all compounds, and it was clarified that they have a stronger inhibitory activity than (S)-Equol (5), which has already been reported to have female hormone-like and anti-androgen effects. From this result, it was confirmed that the 5α-reductase inhibitory activity observed in the Aguahe extract is due to the methoxyflavan compounds. Furthermore, it was confirmed that the methoxyflavan compounds derived from Aguahe (4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, 6,7,4'- tri hydroxy-5-methoxyflavan, 7,8,4'- tri hydroxy-5-methoxyflavan) are useful as 5α-reductase inhibitors.

[0041] Test Example 3. Evaluation of prostate hyperplasia suppression effect 3-1. Changes in the weight of the prostate and seminal vesicles in mice and the inhibitory effect on the expression of prostate-specific antigen (PSA) (1) Preliminary Examination Mice and reagents used in the experiment ICR, 6-7 weeks old, male [Table 4]

[0042] Test Method After allowing the mice to acclimate to the environment for about 3 to 5 days, they were anesthetized with isoflurane and ether, and the testes were removed. The castrated mice were observed for one week. Then, testosterone propionate solution (dissolved in corn oil) was administered subcutaneously to the mice (5 mg / kg), and the test substance was orally administered (the test substance was dissolved in gum arabic and purified water). After these operations were performed for two weeks, the prostate and seminal vesicles were removed and weighed. (N=6) The results are shown in Figure 1. In addition, the degree of inflammation of the prostate was confirmed by confirming the gene expression level of prostate specific antigen (PSA), which is recognized as a biomarker for benign prostatic hyperplasia. The results are shown in Figure 2. The gene expression level was confirmed using the RT-PCR method. Finasteride, a treatment drug for benign prostatic hyperplasia (5AR inhibitor) that is a positive target, was used as the test substance.

[0043] As shown in Figure 1, a significant reduction in prostate weight was confirmed in the group administered 1 mg / kg finasteride. Furthermore, the degree of inflammation in the prostate was confirmed by checking the gene expression level of prostate-specific antigen (PSA), which is recognized as a biomarker for benign prostatic hyperplasia. The gene expression level was confirmed using RT-PCR. As shown in Figure 2, it was also revealed that the PSA gene expression level was almost nonexistent in the Normal group (also in Figure 1, the prostate weight in the Normal group was clearly lighter than that in the Control group). This suggested that testosterone was involved in the overexpression of PSA. Furthermore, the PSA gene expression level was significantly reduced in the group administered 1 mg / kg finasteride. This confirmed that this evaluation test was valid, as the prostate weight was reduced by the drug finasteride, which is a treatment for benign prostatic hyperplasia, and the gene expression level of PSA, a marker for benign prostatic hyperplasia, was reduced.

[0044] (2) Main Test The same method as the above-mentioned preliminary test was used to test the aguaje extract of this example, and the results are shown in Figure 3 (prostate and seminal vesicles) and Figure 4 (gene expression level of PSA).

[0045] (3) Results and Effects of the Examples in Test Example 3-1 As shown in Figure 3, no significant change was observed in seminal vesicle weight due to the aguaje extract. A significant decrease in prostate weight was observed due to the administration of the aguaje extract. In addition, as shown in Figure 4, a decrease in the gene expression level of PSA, a biomarker for benign prostatic hyperplasia, was confirmed. This confirmed that the aguaje extract is useful as a PSA gene expression inhibitor and as a drug for benign prostatic hyperplasia.

[0046] 3-2. Evaluation of the effect of suppressing prostate-specific antigen (PSA) protein and gene expression in human prostate cancer cells (LNCaP cells) Using human prostate cancer cells (LNCaP cells), we investigated the effects of components obtained by examining Aguaje fruit on the protein and gene expression levels of PSA in prostate cancer cells. The experimental method is as follows. (1) Preliminary Examination (1-1) Confirmation of PSA protein expression in LNCaP cells (Western blotting method) LNCaP cells were cultured at 10 cm2 1.5×10 on a dish 6 The cells were seeded at 15 μL per dish and cultured for one day. The medium was then replaced with a culture medium containing the test substance and allowed to act for 24 hours. Proteins were then extracted and the protein expression levels were confirmed by Western blotting. (1-2) Confirmation of PSA gene expression level in LNCaP cells (RT-PCR method) LNCaP cells were plated in a 24-well plate at 5.0 × 10 4 The cells were seeded at 500 μL per well and cultured for one day. The medium was then replaced with a culture solution containing the test substance and allowed to act for 24 hours. RNA was then extracted and the gene (mRNA) expression level was confirmed by RT-PCR. First, Genistein, a positive control, was evaluated in the above (1-1) and (1-2). The results are shown in Figure 5 (1-1) and Figure 6 (1-2).

[0047] As shown in Figures 5 and 6, Genistein was found to have the effect of reducing the PSA protein (Figure 5) and the gene expression level involved in the production of the protein (Figure 6) in prostate cancer cells. Aguaje extract was also evaluated in the same manner.

[0048] (2) Main Test The above test was carried out with Genistein using the aguaje extract of Example 1, 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, and 6,7,4'- tri hydroxy-5-methoxyflavan, 7,8,4'- tri The test was carried out using hydroxy-5-methoxyflavan instead. The results are shown in Figure 7 (1-1), Figure 8 (1-2), and Figure 9 ((1-1) in aguaje extract).

[0049] (3) Results and Effects of the Examples in Test Example 3-2 As shown in Figure 7, a tendency to reduce PSA protein was observed for all ingredients. Among them, 7,8,4'-trihydroxy 5-methoxyflavan significantly reduced PSA, confirming the strongest PSA reducing effect. This confirmed that methoxyflavans, especially 7,8,4'-trihydroxy 5-methoxyflavan, are useful as PSA protein expression inhibitors. Furthermore, as shown in Figure 9, it was confirmed that the aguaje extract reduced the PSA protein, confirming that the aguaje extract is useful as an agent for suppressing the expression of PSA protein. In addition, as shown in FIG. 8, a significant decrease in the PSA gene was observed in 4'-hydroxy 5,7-dimethoxyflavan, 7,4'-dihydroxy 5-methoxyflavan, and 6,7,4'-trihydroxy 5-methoxyflavan. This confirmed that methoxyflavans, especially 4'-hydroxy 5,7-dimethoxyflavan, 7,4'-dihydroxy 5-methoxyflavan, and 6,7,4'-trihydroxy 5-methoxyflavan, are useful as PSA gene expression inhibitors. The decrease in gene expression supports the results that the protein expression of PSA in methoxyflavans tended to decrease. This confirmed that these compounds are useful as prostatic hyperplasia inhibitors.

[0050] The following are examples of formulations of the 5α-reductase inhibitor (aguaje extract) according to the present invention. Note that the following formulation examples do not limit the present invention. Formulation example 1: Chewing gum Sugar 53.0wt% Gum base 20.0 Glucose 10.0 Starch syrup 16.0 Fragrance 0.5 5α-Reductase inhibitor 0.5 100.0wt%

[0051] Formulation Example 2: Gummy Reduced maltose 40.0 wt% Granulated sugar 20.0 Glucose 20.0 Gelatin 4.7 Water 9.68 Yuzu juice 4.0 Yuzu flavor 0.6 Dye 0.02 5α-Reductase inhibitor 1.0 100.0 wt%

[0052] Formulation Example 3: Candy Sugar 50.0 wt% Maltose 33.0 Water 14.4 Organic acid 2.0 Spice 0.2 5α-Reductase inhibitor 0.4 100.0 wt%

[0053] Formulation Example 4: Yogurt (Hard - Soft) Milk 41.5 wt% Skim milk powder 5.8 Sugar 8.0 Agar 0.15 Gelatin 0.1 Lactic acid bacteria 0.005 5α - reductase inhibitor 0.4 Spice trace amount Water remainder 100.0 wt%

[0054] Formulation Example 5: Soft drink Fructose - glucose liquid sugar 30.0 wt% Emulsifier 0.5 5α - reductase inhibitor 0.3 Spice appropriate amount Purified water remainder 100.0 wt%

[0055] Formulation Example 6: Tablet confectionery Sugar 76.4 wt% Glucose 19.0 Sucrose fatty acid ester 0.2 5α-reductase inhibitor 0.5 Purified water 3.9 100.0wt%

[0056] Formulation example 7: Soft capsule Brown rice germ oil 47.0wt% Yuzu seed oil 40.0 Emulsifier 12.0 5α-Reductase inhibitor 1.0 100.0wt%

[0057] Formulation Example 8: Tablets Lactose 54.0wt% Crystalline cellulose 30.0 Starch decomposition product 10.0 Glycerin fatty acid ester 5.0 5α-Reductase inhibitor 1.0 100.0wt%

[0058] Formulation example 9: Cosmetic cream Squalane 20.0wt% Beeswax 5.0 Refined Jojoba Oil 5.0 Glycerin 5.0 Glycerin Monostearate 2.0 Polyoxyethylene (20) Sorbitan Monostearate 2.0 5α-reductase inhibitor 2.0 Preservatives (appropriate amount) Fragrance (appropriate amount) Purified water remainder 100.0wt%

[0059] Formulation example 10: Lotion Ethanol 5.0wt% Glycerin 2.0 1,3-Butylene glycol 2.0 Polyethylene oleyl ether 0.5 Sodium citrate 0.1 Citric acid 0.1 5α-reductase inhibitor 0.1 Purified water remainder 100.0wt%

[0060] Formulation example 11: Body gel Macadamia nut oil 2.0wt% Octyldodecyl myristate 10.0 Methylphenylpolysiloxane 5.0 Behenyl Alcohol 3.0 Stearic Acid 3.0 Batyl alcohol 1.0 Glyceryl Monostearate 1.0 Polyoxyethylene sorbitol tetraoleate 2.0 Hydrogenated soy phospholipids 1.0 Ceramide 0.1 Retinol Palmitate 0.1 Preservatives (appropriate amount) Centella asiatica extract 1.0 5α-reductase inhibitor 1.0 1,3-Butylene glycol 5.0 Purified water remainder 100.0wt%

[0061] Formulation example 12: Emulsion Squalane 4.0wt% Vaseline 2.5 Cetanol 2.0 Glycerin 2.0 Lipophilic glyceryl monostearate 1.0 Stearic acid 1.0 L-Arginine 1.0 5α-reductase inhibitor 0.5 Potassium hydroxide 0.1 Aromaceae trace amount Purified water remainder 100.0wt%

[0062] Formulation example 13: Bath additive (liquid) Propylene glycol 50.0wt% Ethanol 20.0 Sodium sulfate 5.0 5α-reductase inhibitor 0.5 Lanolin 0.5 Avocado oil 0.5 Dye 1.5 Fragrance 22.0 100.0wt%

[0063] Formulation example 14: Hair growth agent (pharmaceutical grade) 5α-reductase inhibitor 5.5wt% Tocopherol acetate 0.1 Pantothenyl alcohol 0.2 Dipotassium glycyrrhizinate 0.1 Polyoxyethylene (EO60) hydrogenated castor oil 0.3 Fragrance 0.1 Propylene glycol 2.0 Ethanol 60.0 Purified water balance Total 100.0wt%

[0064] Example 15: Hair tonic Ethanol 60.0wt% Polyoxyethylene hydrogenated castor oil (E.O 60 moles) 0.5 Glycerin 3.0 Menthol 0.2 5α-reductase inhibitor 0.3 Fragrance and coloring (as needed) Ion-exchanged water remainder Total amount 100wt% [Industrial Applicability]

[0065] As described above, the present invention has a 5α-reductase inhibitory effect, and thereby can suppress prostatic hyperplasia, prevent and improve male pattern baldness, and prevent and improve acne.

Claims

1. A 5α-reductase inhibitor containing an ethanol extract of defatted aguaje as an active ingredient.

2. The 5α-reductase inhibitor described in claim 1, characterized in that the ethanol extract of aguaje contains at least one of 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, 6,7,4'-trihydroxy-5-methoxyflavan, and 7,8,4'-trihydroxy-5-methoxyflavan.

3. A 5α-reductase inhibitor containing as an active ingredient at least one of 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, 6,7,4'-trihydroxy-5-methoxyflavan, and 7,8,4'-trihydroxy-5-methoxyflavan.

4. The 5α-reductase inhibitor described in claim 3, characterized in that the 4'-hydroxy-5,7-dimethoxyflavan, 7,4'-dihydroxy-5-methoxyflavan, 6,7,4'-trihydroxy-5-methoxyflavan, and 7,8,4'-trihydroxy-5-methoxyflavan are derived from aguaje.

5. A prostate-specific antigen (PSA) gene expression inhibitor obtained by ethanol extract of defatted aguaje.

6. A prostate-specific antigen (PSA) protein expression inhibitor containing 7,8,4'-trihydroxy 5-methoxyflavan as an active ingredient.

7. A prostate-specific antigen (PSA) gene expression inhibitor comprising at least one of 4'-hydroxy 5,7-dimethoxyflavan, 7,4'-dihydroxy 5-methoxyflavan and 6,7,4'-trihydroxy 5-methoxyflavan as an active ingredient.

8. A prostate-specific antigen (PSA) protein expression inhibitor having an ethanol extract of defatted aguaje as an active ingredient.

9. A prostatic hyperplasia inhibitor comprising the agent according to any one of claims 1 to 9 as an active ingredient.

10. An agent for suppressing male pattern baldness, comprising as an active ingredient a 5α-reductase inhibitor according to any one of claims 1 to 4.

11. An acne prevention and improvement agent comprising the 5α-reductase inhibitor according to any one of claims 1 to 4 as an active ingredient.

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