JP2006306816A - TESTOSTERONE-5alpha-REDUCTASE INHIBITOR AND COSMETIC CONTAINING TESTOSTERONE-5alpha-REDUCTASE INHIBITOR - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a testosterone-5α-reductase inhibitor which has a testosterone-5α-reductase activity-inhibiting action, controls the production of a highly active dihydrotestosterone, has actions for inhibiting hypersteatosis, protein synthesis failure, the blood flow rate decrease of hair follicles, and the lowering of enzyme activity levels, little irritates the skins, has excellent safety for living bodies, and is useful as a raw material for cosmetics, to provide a skin cosmetic which contains a testosterone-5α-reductase inhibitor and improves sebaceous skins, and to provide a hair cosmetic which is effective for preventing alopecia and for growing the hair/restoring the hair. <P>SOLUTION: This testosterone-5α-reductase inhibitor contains an extract of a Zosteraceae, Zostera sp. plant as an active ingredient. The skin or hair cosmetic contains a testosterone-5α-reductase inhibitor containing an extract of a Zosteraceae, Zostera sp. plant as an active ingredient. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a testosterone-5α-reductase inhibitor containing an extract of a marine flowering plant as an active ingredient and a cosmetic containing the inhibitor, and more specifically, by suppressing the production of dehydrotestosterone, The present invention relates to a testosterone-5α-reductase inhibitor exhibiting high effectiveness in preventing or improving overproduction and hair loss, and a skin cosmetic and hair cosmetic containing the inhibitor.

  Changes in sebum secretion are closely related to keratinization and hair loss of the epidermis, and sebum secretion is known to be regulated by various hormones. In particular, the regulation of sebum secretion in sebaceous glands and hair follicles is thought to depend on the secretion of male hormone testosterone and the production of dihydrotestosterone. In diseases such as androgenetic alopecia or hirsutism, suppurative dysplasia or prostate cancer, which is considered to be caused by dysfunction of apocrine glands, the effects of male hormones may be the cause or It is considered an exacerbating factor, and various anti-androgen drugs are used to treat these diseases. However, it is known that congenital testosterone-5α-reductase deficiency does not show enlargement of the prostate, male pattern baldness does not develop, and acne is mild if possible. In fact, it is becoming clear that testosterone is dihydrotestosterone produced by reduction of testosterone-5α-reductase, which exhibits physiological effects in the prostate, hair follicle and sebaceous glands. In addition, increased activity of dihydrotestosterone is considered to be the main factor causing increased secretion of sebum, or hair matrix cell level protein synthesis failure, hair follicle blood flow rate decrease, and enzyme activity level decrease in the scalp. Testosterone-5α-reductase, which is involved in reducing testosterone to dihydrotestosterone, a more active male hormone, in order to suppress oily skin and hair loss caused by such excessive production and increased activity of dihydrotestosterone Inhibiting activity is considered effective and various testosterone-5α-reductase inhibitors have been developed.

For example, progesterone progesterone, oxendron (JP 59-59606) and chlormadinone acetate (JP 59-98010) are known to use anti-androgen agents, and the plant component is testosterone-5α. -Examples of use as a reductase inhibitor include solvent extraction extracts of herbal medicines selected from the group consisting of tocopheryl quinone (Japanese Patent Laid-Open No. 58-19389), asenyaku, fennel, etc., Japanese Patent No. 60-146829, An aqueous extract (Japanese Patent Laid-Open No. Sho 62-116520) and an extract obtained from walnut leaves and / or peels (Japanese Patent Laid-Open No. Sho 63-203625) are known.
However, these conventional testosterone-5α-reductase inhibitors have problems in that they have insufficient inhibitory activity or have systemic side effects. For example, progesterone is a potent testosterone-5α-reductase inhibitor, but due to its progesterone action, it causes decreased libido, impotence, female breasts and the like. In addition, among other inhibitors, anti-androgenic agents are often composed of steroids or structural formulas similar thereto, for example, cyclic triterpenes, etc., except for hormone-like effects that are somewhat undesirable or testosterone-5α-reductase inhibitory effects. May also have hormone-inhibiting activity, while those using plant components generally have low side effects and high safety, but are not always satisfactory in terms of inhibitory activity. There is a difficulty that cannot be said.
Therefore, it is clear that a testosterone-5α-reductase inhibitor that is highly active and has no safety problems is desired.

JP 59-59606 JP 59-98010 Japanese Patent Laid-Open No. 58-193689 JP 60-146829 A JP 62-116520 A JP 63-203625 A

  The present invention has been made in view of the problems of the prior art as described above, and the object of the present invention is to improve the oily skin, which is an excessive sebum secretion state as a skin care, the effect of acne treatment, the scalp, the hair Is to provide a testosterone-5α-reductase inhibitor excellent in hair loss prevention, hair-restoration / hair-growth effects and high safety, and skin and hair cosmetics containing the inhibitor.

As a result of intensive studies to achieve the above object, the present inventors have been used as a cosmetic composition raw material because of the excellent skin beautifying effect based on the keratin function soundening action and the moisturizing action, and the safety is supported. In addition to the above-mentioned skin beautifying effect, the marine flowering plant extract has the effect of remarkably suppressing the activity of testosterone-5α-reductase, and thus has both effectiveness and safety. It was learned that it was possible to provide a testosterone-5α-reductase inhibitor, and the present invention was completed.
That is, the present invention first provides a testosterone-5α-reductase inhibitor comprising an extract of a marine flowering plant as an active ingredient.
Secondly, the present invention provides skin cosmetics and hair cosmetics containing a testosterone-5α-reductase inhibitor containing an extract of a marine flowering plant as an active ingredient.
In the present invention, the term cosmetic is used in a broad sense including so-called cosmetics and quasi-drugs.

  The testosterone-5α-reductase inhibitor of the present invention comprising an extract of a marine flowering plant as an active ingredient suppresses biosynthesis of dihydrotestosterone, a highly active male hormone, and causes seborrheic eczema and acne bacteria in the skin. It suppresses the occurrence of acne and oily skin, suppresses protein synthesis failure at the hair matrix level in the scalp, decreases the blood flow of hair follicles, and decreases the level of enzyme activity, and has the effect of hair growth and hair restoration. Moreover, the skin cosmetics and hair cosmetics of the present invention comprising the testosterone-5α-reductase inhibitor described above are used for improving oily skin, preventing and treating acne, preventing hair loss, and nourishing hair. In addition to exhibiting excellent effects, it is highly safe, and there is no fear of adversely affecting the living body even after long-term use.

Hereinafter, the present invention will be described in detail.
As the marine flowering plant used for the preparation of the testosterone-5α-reductase inhibitor of the present invention, it is preferable to use a plant of the genus Zostera sp. As the genus Amamo, for example, Zostera marina, Zostera japonica, Zostera asiatica, Sugaamapa (Zostera caespitosa), Tachiamamo (Zostera caulescens), etc., in the present invention, all the plants of the genus Amamo are preferably used as extraction raw materials.
Among these genus Amamo plants, it is most preferable to use the whole plant of Amamo [Zostera marina] from the viewpoint of the testosterone-5α-reductase inhibitory action of the extract.

  Preparation of the extracts of these marine flowering plants is carried out by appropriately washing the site to be extracted, for example, the whole plant, if necessary, by pre-washing and drying, preferably further chopped or pulverized, and then by an appropriate method such as a dipping method or countercurrent extraction method. By contacting the extraction solvent by means.

As an extraction solvent, water; lower alcohols such as methanol, ethanol, and propanol; higher alcohols such as oleyl alcohol, stearyl alcohol, and octyldodecanol; various solvents such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin Monohydric alcohols; esters such as ethyl acetate, butyl acetate, methyl propionate and 2-ethylhexyl glyceride; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether and isopropyl ether; n-hexane, toluene and chloroform Examples thereof include hydrocarbon solvents, which are used alone or in combination of two or more.
Among these, it is preferable to use one kind of single solvent or two or more kinds of mixed solvents selected from water, lower alcohols and polyhydric alcohols from the viewpoint that they can be widely applied to cosmetics. Single use is most preferred.

  The mixing ratio in the case of using a mixed solvent is, for example, 1: 1 to 25: 1 by volume ratio (hereinafter the same) if the mixed solvent is water and ethyl alcohol, and 1: if the mixed solvent is water and glycerin. In the case of a mixed solvent of 1 to 20: 1, or water and 1,3-butylene glycol, it is preferably in the range of 1: 1 to 20: 1.

  In the preparation of the extract of the present invention, the pH of the extract is preferably maintained in the range of 4 to 8. In this sense, if necessary, the extraction solvent may be sodium hydroxide, sodium carbonate, potassium hydroxide. Alternatively, an alkaline adjusting agent such as arginine, an acidic adjusting agent such as citric acid, hydrochloric acid, phosphoric acid, sulfuric acid, or the like may be blended to adjust to a desired pH.

  In the case of the dipping method, the amount ratio of the extraction solvent to the substance to be extracted is generally in the range of 1: 1 to 1: 200 (weight ratio), preferably in the range of 1:15 to 1:35.

  Moreover, although extraction conditions, such as extraction temperature and time, also differ depending on the type of solvent used, the extraction site of the plant, and the degree of shredding, for example, in the case of the immersion method, the extraction temperature is generally 4 to 80 ° C., The temperature is preferably in the range of 40 ° C. or less, and the extraction time is preferably about 0.1 to 1 week, particularly about 12 to 24 hours.

  The extract solution obtained here may generally be adjusted to a pH of 4 to 8 and then mixed as it is, or it may be adjusted to an appropriate concentration by dilution or concentration under reduced pressure, etc. Depending on the case, it may be pulverized according to a conventional method such as spray drying or freeze drying, and then blended into the cosmetic.

The above extract solution has good storage stability that can be satisfactorily satisfied in practice as it is, but if necessary, it can be subjected to hydrolysis treatment to exert testosterone-5α-reductase inhibitory action. The storage stability can be further enhanced without any loss.
The hydrolysis treatment may be performed by either a method using an enzyme or a method using an acid or an alkali, but preferably an enzyme hydrolysis treatment is used.

In the case of performing an enzyme hydrolysis treatment, for example, a fibrinolytic enzyme such as cellulase, hemicellulase or ligninase, a starch degrading enzyme such as α-amylase, β-amylase or glucoamylase, or a pectin degrading enzyme such as pectinase is used as the enzyme. Preferably, a combination of one or more enzymes selected from the above enzyme group is used.
The hydrolysis treatment with these enzymes uses 0.001 to 10% by weight, preferably 0.1 to 1% by weight of the enzyme in total amount based on the solid content of the extract solution. It is carried out by treating for 1 to 24 hours near the optimum temperature.

  On the other hand, when performing an acid or alkali hydrolysis treatment, an acid adjuster such as hydrochloric acid, phosphoric acid or sulfuric acid is used for the acid hydrolysis treatment, and sodium hydroxide or carbonate is used for the alkali hydrolysis treatment. If alkaline adjusters such as sodium and potassium hydroxide are used respectively, the pH of the extract solution is adjusted to 3 or lower or 8.5 or higher, and this is maintained at 60 to 90 ° C. for 1 to 6 hours. Good.

  The extract of the marine flowering plant of the present invention prepared as described above has an action of strongly inhibiting the activity of testosterone-5α-reductase as shown in Test Examples later, and has little skin irritation. It has excellent biological safety and is useful as a testosterone-5α-reductase inhibitor for cosmetics and the like.

  As cosmetics of the present invention containing such a testosterone-5α-reductase inhibitor, for example, skin cosmetics, basic cosmetics such as emulsions, creams, lotions, essences, packs, facial cleansers, lipsticks, foundations, liquid foundations, Makeup cosmetics such as makeup press powder, facial cleansers, body shampoos, soaps and other cleaning cosmetics, as well as bath preparations, as hair cosmetics, hair restorer, hair shampoo, hair rinse, hair treatment, Conditioners, hair dyes, hair nail polishes, hair styling agents and the like can be mentioned, but the present invention is not limited to these.

  The amount of the testosterone-5α-reductase inhibitor in the cosmetic composition of the present invention is the solid content of the marine flowering plant extract as its active ingredient. Is generally in the range of 0.00001 to 5% by weight, preferably in the range of 0.001 to 3% by weight. For makeup cosmetics, it is generally in the range of 0.00001 to 5% by weight, preferably in the range of 0.001 to 2% by weight. For cleaning cosmetics, it is generally in the range of 0.0001 to 10% by weight, preferably 0.001 to 5% by weight, whereas for hair cosmetics, it is generally 0.0001 to 10% by weight, preferably It is in the range of 0.001 to 5% by weight.

  In addition to the essential testosterone-5α-reductase inhibitor, the cosmetics of the present invention include components usually used in cosmetics such as oily components, surfactants, moisturizers, thickeners, antiseptic / bactericides. , Powder components, ultraviolet absorbers, antioxidants, pigments, fragrances, bioactive components, and the like can be appropriately blended as necessary.

  Here, as the oil component, for example, olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice germ oil, palm oil, palm oil, cacao oil, meadow foam oil, sheer butter, tea tree oil, avocado oil, Oils derived from plants such as macadamia nut oil and plant-derived squalane; Fats derived from animals such as mink oil and turtle oil; waxes such as beeswax, carnauba wax, rice wax, lanolin; liquid paraffin, petrolatum, paraffin wax, squalane, etc. Hydrocarbons; fatty acids such as myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, cis-11-eicosenoic acid; higher alcohols such as lauryl alcohol, cetanol, stearyl alcohol; isopropyl myristate, palmitic acid Isopropyl, me Butyl phosphate, 2-ethylhexyl glycerides, higher fatty acid octyldodecyl (octyl stearate dodecyl and the like), and the synthetic esters and synthetic triglycerides such like.

Examples of the surfactant include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene Nonionic surfactants such as oxyethylene sorbitol fatty acid esters; fatty acid salts, alkyl sulfates, alkylbenzene sulfonates, polyoxyethylene alkyl ether sulfates, polyoxyethylene fatty amine sulfates, polyoxyethylene alkyl phenyl ether sulfates, Polyoxyethylene alkyl ether phosphates, α-sulfonated fatty acid alkyl ester salts, polyoxyethylene alkyl phenyl ether phosphates Quaternary ammonium salts, primary to tertiary fatty amine salts, trialkylbenzylammonium salts, alkylpyridinium salts, 2-alkyl-1-alkyl-1-hydroxyethylimidazolinium salts, N Cationic surfactants such as N, N-dialkylmorphonium salt, polyethylene polyamine fatty acid amide salt; N, N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine, N, N, N-trialkyl-N- Amphoteric surfactants such as alkylene ammoniocarboxybetaine and N-acylamidopropyl-N ′, N′-dimethyl-N′-β-hydroxypropylammoniosulfobetaine can be used.
In addition, as emulsifiers or emulsifiers, stevia derivatives such as enzyme-treated stevia, lecithin and derivatives thereof, lactic acid bacteria fermented rice, lactic acid bacteria fermented rice, lactic acid bacteria fermented cereals (wheat, beans, millet, etc.), juzyiro (Rhamnaceae) ) An extract or the like can also be blended.

  Examples of humectants include glycols such as glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol and polyethylene glycol, sugars such as maltitol, sorbitol, xylitol, trehalose and glucose, sodium pyrrolidonecarboxylate, lactic acid bacteria fermentation Rice, mucopolysaccharide (eg, hyaluronic acid and its derivatives, chondroitin and its derivatives, heparin and its derivatives), elastin and its derivatives, collagen and its derivatives, hydrolyzed silk protein, NMF related substances, lactic acid, urea, high grade Fatty acid octyldodecyl, phytosterol, soybean phospholipid, cholesteryl isostearate, seaweed extract, seafood-derived collagen and its derivatives, various amino acids and their derivatives (for example, trime Rugurishin, etc.) and the like.

  Examples of thickeners include, for example, brown algae such as alginic acid, agar, carrageenan, fucoidan, green algae or red algae-derived components, extract of sand cucumber, pectin, locust bean gum, polysaccharides such as aloe polysaccharide, xanthan gum, tragacanth gum, guar gum, etc. Synthetic polymers such as gums, cellulose derivatives such as carboxymethylcellulose, hydroxyethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylic acid / methacrylic acid copolymer; hyaluronic acid and its derivatives, polyglutamic acid and its derivatives, etc. Is mentioned.

  Examples of the antiseptic / bactericidal agent include urea; paraoxybenzoates such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate; phenoxyethanol, dichlorophene, hexachlorophene, chlorhexidine hydrochloride, benzaza chloride There are extracts of a plant of the genus Genus such as Luconium, Salicylic acid, Ethanol, Undecylenic acid, Phenols, Jamal (Imidazodenyl urea), 1,2-pentanediol, Udo, various essential oils, bark distillate and the like.

  Examples of powder components include sericite, titanium oxide, talc, kaolin, bentonite, zinc oxide, magnesium carbonate, magnesium oxide, zirconium oxide, barium sulfate, anhydrous silicic acid, mica, 6- or 12-nylon powder, polyethylene powder Silk powder, cellulosic powder, grains (rice, wheat, corn, millet, etc.) powder, beans (soybean, red beans, etc.) powder, and the like.

  Examples of the ultraviolet absorber include ethyl paraaminobenzoate, ethylhexyl paradimethylaminobenzoate, amyl salicylate and derivatives thereof, 2-ethylhexyl paramethoxycinnamate, octyl cinnamate, oxybenzone, 2,4-dihydroxybenzophenone, 2-hydroxy-4 -Methoxybenzophenone-5-sulfonate, 4-tertiarybutyl-4-methoxybenzoylmethane, 2- (2-hydroxy-5-methylphenyl) benzotriazole, urocanic acid, ethyl urocanate, aloe extract, etc. .

  Examples of antioxidants include bioactive oxygen-degrading enzymes such as superoxide dismutase and catalase, vitamins such as vitamin E and vitamin D and derivatives thereof, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, Ubidecaquinone (ubiquinone), rutin, rutin glucoside, γ-oryzanol, ginkgo biloba extract, age extract, psycho extract, birch extract, birch extract, plum extract, evening primrose extract, june extract Melissa extract, white coconut extract, rice extract, murasakixikibu extract, oolong tea extract and the like.

  Examples of physiologically active ingredients include whitening ingredients such as tranexamic acid and derivatives thereof, t-cycloamino acid derivatives, kojic acid and derivatives thereof, hydroquinone derivatives, ellagic acid and derivatives thereof, resorcinol derivatives, placenta extract, cysteine, and sohachi extract , Yukinoshita extract, rice bran extract, rice bran extract hydrolyzate, lactic acid bacteria fermented rice, lactic acid bacteria fermented germinated rice, lactic acid bacteria fermented cereals (wheat, legumes, minor grains), white coconut hydrolyzed extract, murasakiki kib extract, lotus Fermented sesame extract, extract of ginseng, Pandanus amaryllifolius Roxb. Extract, Arcangelicia flava Merrilli extract, chamomile extract (trade name: Camomile ET) Extract, Hamamelis extract, Japanese knotweed extract, Sawade primrose extract, Licorice extract, Japanese dandelion extract, Artea extract, Gennosho extract, Yukinoshita extract, Jujube extract, Peonies extract, Toki extract, Peach extract Extracts of seaweeds such as green algae, red algae or brown algae, seaweeds such as sea cucumber, linoleic acid and its derivatives or processed products (eg liposomal linoleic acid), 2,5-dihydroxybenzoic acid derivatives, etc. As skin aging prevention and skin beautifying ingredients, animal or fish-derived collagen and derivatives thereof, elastin and derivatives thereof, intercellular lipids such as ceramide, placental extract, nicotinic acid and derivatives thereof, glycyrrhizic acid and derivatives thereof (dipotassium salt, etc.) ), T-cycloamino acid derivatives, vitamin A precursor, vitamin A and its derivatives Body, vitamin E and its derivatives, allantoin, α-hydroxy acids, diisopropylamine dichloroacetate, γ-amino-β-hydroxybutyric acid, coenzyme Q-10, α-lipoic acid, carnitine and its derivatives, gentian extract, licorice extract, Herb extract, chamomile extract, carrot extract, aloe extract, cuckoo extract and other herbal extracts, rice extract hydrolyzate, rice bran extract hydrolysate, rice fermentation extract, green algae, red algae or brown algae seaweed extract , Seaweed extracts such as sea cucumbers, Sahaku extract, Zizyhus juazeiro extract, beech extract, Kidachi aloe extract, Mannenrou extract, Ginkgo biloba extract, Japanese horsetail extract, safflower extract, ginseng extract, carrot extract , Elder Co-extract, Hagoromogusa extract, Tabebuia impetiginosa extract, yeast extract, eggshell membrane extract protein, deoxyribonucleic acid potassium salt and the like, and as an anti-inflammatory agent, an azulene derivative such as sodium guaiazulene sulfonate, ethyl guaiazulene sulfonate, Glycyrrhizic acid derivatives such as dipotassium glycyrrhizinate and stearyl glycyrrhizinate, allantoin, licorice extract, cucumber extract, peony extract, button pi extract, forsythia extract, ryutan extract, red snapper extract, parsley extract, hypericum extract Products, Bukuryotake extract, Cassia extract, etc.

  Examples of the kojic acid derivatives include kojic acid esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid dibutyrate, kojic acid ethers, kojic acid sugar derivatives such as kojic acid glucoside, etc. As the ascorbic acid derivatives, for example, L-ascorbic acid-2-phosphate sodium, L-ascorbic acid-2-phosphate magnesium, L-ascorbic acid-2-sulfate sodium, L-ascorbic acid-2 -Ascorbic acid ester salts such as magnesium sulfate, L-ascorbic acid-2-glucoside (2-O-α-D-glucopyranosyl-L-ascorbic acid), L-ascorbic acid-5-glucoside (5-O-α) -D-Glucopyranosyl-L-ascorbine Acid) ascorbic acid sugar derivatives, acylated 6-positions of these ascorbic acid sugar derivatives (acyl groups are hexanoyl, octanoyl, decanoyl, etc.), L-ascorbic acid tetraisopalmitate, L-ascorbic acid tetra L-ascorbic acid tetra-fatty acid esters such as lauric acid ester, 3-O-ethylascorbic acid, L-ascorbic acid-2-phosphate-6-O-palmitate sodium, etc. include arbutin (hydroquinone) -Β-D-glucopyranoside), α-arbutin (hydroquinone-α-D-glucopyranoside) and the like, and as the resorcinol derivative, for example, 4-n-butylresorcinol, 4-isoamylresorcinol and the like are 2,5-dihydroxybenzoic acid. Derivatives and For example, 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, 2-hydroxy-5-propionyloxybenzoic acid, etc., and nicotinic acid derivatives include, for example, nicotinic acid amide, benzyl nicotinate, etc. However, examples of vitamin E derivatives include vitamin E nicotinate, vitamin E linoleate, and vitamin E phosphate sodium salt, and examples of α-hydroxy acids include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctane. There are acids.

  Next, although an Example, a test example, and a formulation example (Example of cosmetics) are given and this invention is demonstrated further more concretely, this invention is not limited to them. In the following, all parts are parts by weight, and all% are% by weight.

Example 1. Preparation of testosterone-5α-reductase inhibitor (1)
Purified water (1000 g) was mixed with 50 g of whole slices of sea cucumber, extracted at 60 ° C. for 4 hours and filtered to obtain 850 g of a light brown transparent testosterone-5α-reductase inhibitor (solid content: 0) .5%).

Example 2 Preparation of testosterone-5α-reductase inhibitor (2)
100 g of sliced whole leglins are mixed with 900 g of a 7: 3 (weight ratio) mixture of purified water and 1,3-butylene glycol, extracted at 4 ° C. for 1 week, filtered, and light brown transparent 720 g of testosterone-5α-reductase inhibitor was obtained (solid content concentration 0.9%).

Example 3 Preparation of testosterone-5α-reductase inhibitor (3)
Purified water (1000 g) was mixed with 100 g of whole slices of sea cucumber, extracted at 80 ° C. for 2 hours, and then filtered. To the filtrate, 0.005% each of cellulase of fibrinolytic enzyme, glucoamylase of starch degrading enzyme, and pectinase of pectin degrading enzyme were added and subjected to hydrolysis treatment at 40 ° C. for 2 hours, followed by 80 ° C., 1 The enzyme was inactivated over time and filtered to obtain 660 g of a light brown transparent testosterone-5α-reductase inhibitor (solid content concentration 1.0%).

Example 4 Preparation of testosterone-5α-reductase inhibitor (4)
840 g of a light yellow transparent light brown transparent testosterone-5α-reductase inhibitor was obtained (solid content concentration 0.6%) in the same manner as in Example 1 except that cored eel was used instead of sea eel.

Embodiment 5 FIG. Preparation of testosterone-5α-reductase inhibitor (5)
640 g of a light yellow transparent, light brown transparent testosterone-5α-reductase inhibitor was obtained (solid content concentration 0.9%) in the same manner as in Example 3 except that eelgrass was used instead of sea eel.

Example 6 Preparation of testosterone-5α-reductase inhibitor (6)
500 g of the testosterone-5α-reductase inhibitor solution prepared in the same manner as in Example 1 was freeze-dried and then pulverized to obtain 2.3 g of a tan brown testosterone-5α-reductase inhibitor powder.

Test Example 1 Testosterone-5α-reductase inhibition test The testosterone-5α-reductase inhibitory activity of the extract solution obtained in the example (testosterone-5α-reductase inhibitor) was examined using rat liver homogenate.
[sample]
(1) Extract solution of Example 1 (testosterone-5α-reductase inhibitor)
(2) Extract solution of Example 3 (testosterone-5α-reductase inhibitor)
(3) Extract solution of Example 4 (testosterone-5α-reductase inhibitor)
(4) Ethinyl estradiol (positive control)
[Test method]
(A) Enzymatic reaction The extract solution of each example was diluted 1.48 times with water (to make the final concentration in the test system 5%) and used as a sample. The positive control ethinyl estradiol was also dissolved in ethanol so that the final concentration was 5%.
1 mL of a 500 μg / mL testosterone solution (solvent: propylene glycol / 10 mM Tris-HCl buffer (pH 7.2) = 1/1) was added to 0.2 mL of the sample and mixed.
To this, 1 mL of rat liver-derived S-9 (manufactured by Oriental Yeast Co., Ltd.) was added, and a 0.77 mg / mL NADPH solution (solvent: 10 mM Tris-HCl buffer (pH 7.2)) 0. 5 mL was added and the enzyme reaction was performed at 37 ° C. for 30 minutes. Next, 5 mL of dichloromethane was added to stop the enzyme reaction, and 0.1 mg / mL of p-hydroxybenzoic acid n-propyl ester solution (solvent: methanol) was added as an internal standard (hereinafter referred to as “IS”) to a concentration of 0. After adding 5 mL and stirring, it centrifuged at 900 xg for 10 minutes, and the lower layer (organic phase) was extract | collected. The collected organic phase was concentrated to dryness under reduced pressure, and the dried product was dissolved in 5 mL of methanol to prepare a sample for high pressure liquid chromatography (hereinafter referred to as HPLC).
(B) Quantification of residual testosterone by HPLC The HPLC conditions were as follows.
Column; TSK-GEL ODS-80Ts (150 × 4.6 mm ID)
Temperature; 40 ° C
Mobile phase; methanol-water (65:35)
Flow rate; 0.5 mL / min Detection; Ultraviolet region 254 nm
Retention time; Testosterone 15 min. S. 8 minutes.
Injection volume; 10 μL
At the same time, the same operation was performed for a system in which dichloromethane was added before NADPH was added as a control (0 minutes) and a system in which purified water was added instead of the sample as a control (30 minutes).
Testosterone-5α-reductase inhibitory activity was calculated by the formula shown below.
Inhibition rate (%) =
Peak area ratio of sample-peak area ratio of control (30 minutes)
Peak area ratio of control (0 minutes)-peak area ratio of control (30 minutes) The peak area ratio referred to here is the peak area of testosterone. S. The quotient when divided by the peak area.

[result]
The results are shown in Table 1.
As shown in Table 1, the extract of the genus Amamoaceae (testosterone-5α-reductase inhibitor of Example 1) has an effect of significantly inhibiting the activity of testosterone-5α-reductase.

Formulation Example 1 Cream [component A] part Liquid paraffin 5.0
Hexalan (Note 1) 4.0
Paraffin 5.0
Glyceryl monostearate 2.0
Polyoxyethylene (20) sorbitan monostearate 6.0
Butylparaben 0.1
(Note 1) 2-ethylhexyl glyceride [Component B] manufactured by Technoble Co., Ltd.
Testosterone-5α-reductase inhibitor of Example 1 10.0
Glycerin 5.0
Methylparaben 0.1
Moiston C (Note 2) 1.0
Amount of purified water totaling 100 parts
(Note 2) NMF component manufactured by Technoble Co., Ltd.
[C component]
Perfume
The components A and B were each heated to 80 ° C. or higher and then mixed by stirring. After this was cooled to 50 ° C., component C was added and further stirred and mixed to obtain a cream.

Formulation Example 2 Cream A cream was obtained in the same manner as in Formulation Example 1 except that the testosterone-5α-reductase inhibitor of Example 2 was used instead of the testosterone-5α-reductase inhibitor of Example 1 in the component B of Formulation Example 1.

Formulation Example 3 Emulsion [component A] part liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
Methylparaben 0.15
Ethylparaben 0.03
[B component]
Testosterone-5α-reductase inhibitor of Example 1 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethylcellulose 0.3
Sodium hyaluronate 0.01
Amount of purified water totaling 100 parts
[C component]
Perfume
The components A and B were each heated to 80 ° C. or higher and then mixed by stirring. After cooling this to 50 ° C., component C was added and further stirred and mixed to obtain an emulsion.

Formulation Example 4 Lotion [component] part Testosterone-5α-reductase inhibitor of Example 3 10.0
Ethanol 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Methylparaben 0.2
Citric acid 0.1
Sodium citrate 0.3
Carboxyvinyl polymer 0.1
Perfume
Potassium hydroxide appropriate amount Purified water Amount that makes 100 parts in total
The above ingredients were mixed to obtain a lotion.

Formulation Example 5 Lotion [component A] part olive oil 1.0
Polyoxyethylene (5.5) cetyl ether 0.5
Butylparaben 0.1
[B component]
Testosterone-5α-reductase inhibitor of Example 4 10.0
Ethanol 5.0
Glycerin 5.0
1,3-butylene glycol 5.0
Methylparaben 0.1
Potassium hydroxide appropriate amount Purified water Amount that makes 100 parts in total
[C component]
Perfume
After each component A and component B was heated to 80 ° C. or higher, the component B was added to the component A and stirred, and further homogenized with Hiscotron (5000 rpm) for 2 minutes.
After cooling this to 50 degreeC, C component was added and stirred and mixed, and also it cooled to 30 degrees C or less, and the lotion was obtained.

Formulation Example 6 Emulsion An emulsion was obtained in the same manner as in Formulation Example 3 except that the testosterone-5α-reductase inhibitor of Example 2 was used instead of the testosterone-5α-reductase inhibitor of Example 1 in the B component of Formulation Example 3.

Formulation Example 7 Emulsion An emulsion was obtained in the same manner as in Formulation Example 3 except that the testosterone-5α-reductase inhibitor of Example 1 was used instead of the testosterone-5α-reductase inhibitor of Example 1 in the component B of Formulation Example 3.

Formulation Example 8 Emulsion An emulsion was obtained in the same manner as in Formulation Example 3, except that the testosterone-5α-reductase inhibitor of Example 1 was used instead of the testosterone-5α-reductase inhibitor of Example 1 in the component B of Formulation Example 3.

Formulation Example 9 Emulsion [component A] part liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
Methylparaben 0.15
Ethylparaben 0.03
[B component]
Testosterone-5α-reductase inhibitor of Example 1 10.0
L-Ascorbic acid-2-glucoside 2.0
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethylcellulose 0.3
Sodium hyaluronate 0.01
Potassium hydroxide 0.5
Purified water Amount of 100 parts [component C]
Fragrance Appropriate amount Each of the above components A and B was heated to 80 ° C. or higher, and then mixed by stirring. After cooling this to 50 ° C., component C was added and further stirred and mixed to obtain an emulsion.

Formulation Example 10 Emulsion In addition to using 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in component B of Formulation Example 9, 2.0 parts of magnesium L-ascorbyl-2-phosphate is used. Gave a milky lotion in the same manner as in Formulation Example 9.

Formulation Example 11 Emulsion In addition to using 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in component B of Formulation Example 9, 2.0 parts of sodium L-ascorbic acid-2-phosphate is used. Gave a milky lotion in the same manner as in Formulation Example 9.

Formulation Example 12. Emulsion In the same manner as Formulation Example 9, except that 2.0 parts of arbutin is used instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide in the B component of Formulation Example 9. Obtained.

Formulation Example 13 Emulsion In place of component B in Formulation Example 9, instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide, a rice bran extract hydrolyzate (trade name “Grace Know” manufactured by Technoble Co., Ltd.) * Snow * HP ", solid content concentration 3.5%) An emulsion was obtained in the same manner as in Formulation Example 9, except that 5.0 parts were used.

Formulation Example 14. Latex In the B component of Formulation Example 9, in place of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide, white seed (Brassica Alba) seed extract (trade name, manufactured by Technoble Co., Ltd.) An emulsion was obtained in the same manner as in Formulation Example 9 except that 5.0 parts of “Sinablanca-WH” (solid content concentration 1.0%) were used.

Formulation Example 15. Emulsion Formulation Example 9 except for using 1.0 part of γ-amino-β-hydroxybutyric acid instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide in the B component of Formulation Example 9. In the same manner as in No. 9, an emulsion was obtained.

Formulation Example 16. Emulsion In place of the B component of Formulation Example 9, instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 part of potassium hydroxide, a rice extract hydrolyzate (trade name “Orisenoble, manufactured by Technoble Co., Ltd.) A solid emulsion was obtained in the same manner as in Formulation Example 9 except that 5.0 parts of a solid content concentration of 1.5% was used.

Formulation Example 17. Emulsion [component A] part liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
Coenzyme Q-10 0.01
Methylparaben 0.15
Ethylparaben 0.03
[B component]
Testosterone-5α-reductase inhibitor of Example 1 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethylcellulose 0.3
Sodium hyaluronate 0.01
Purified water Amount of 100 parts [component C]
Fragrance Appropriate amount Each of the above components A and B was heated to 80 ° C. or higher, and then mixed by stirring. After cooling this to 50 ° C., component C was added and further stirred and mixed to obtain an emulsion.

Formulation Example 18. Lotion [component] part Testosterone-5α-reductase inhibitor of Example 1 10.0
L-Ascorbic acid-2-glucoside 2.0
Ethanol 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Methylparaben 0.2
Citric acid 0.1
Sodium citrate 0.3
Sodium alginate 0.1
Potassium hydroxide 0.5
Perfume
Amount of purified water totaling 100 parts
The above ingredients were mixed to obtain a lotion.

Formulation Example 19. Pressed powder [A component] Part Bengala 0.5
Yellow iron oxide 1.5
Black iron oxide 0.1
Titanium oxide 10.0
6-Nylon powder 4.0
Amount that makes 100 parts of sericite Mica 23.0
Talc 25.0
Testosterone-5α-reductase inhibitor of Example 6 0.1
[B component]
Squalane 1.0
Methylpolysiloxane 4.0
Propylparaben 0.1
Dehydroacetic acid 0.1
Liquid paraffin 2.0
Perfume
The above A component and B component were mixed and stirred, mixed, then passed through a 200 mesh Tyler mesh sieve, and the resulting mixed powder was cast into a mold to obtain a pressed powder.

Formulation Example 20. Liquid foundation [component A] part Stearic acid 2.4
Propylene glycol monostearate 2.0
Cetostearyl alcohol 0.2
Liquid lanolin 2.0
Liquid paraffin 3.0
Isopropyl myristate 8.5
Propylparaben 0.05
[B component]
Testosterone-5α-reductase inhibitor of Example 2 5.0
Sodium carboxymethylcellulose 0.2
Bentonite 0.5
Propylene glycol 4.0
Triethanolamine 1.1
Methylparaben 0.1
Purified water Amount that makes the total amount 100 parts [C component]
Titanium oxide 8.0
Talc 4.0
Coloring pigment appropriate amount The components A and B were heated and mixed and stirred. This was reheated, the above C component was added, poured into a mold, and stirred until it reached room temperature to obtain a liquid foundation.

Example 21. Cream foundation [component A] part Stearic acid 5.0
Cetanol 2.0
Glyceryl monostearate 3.0
Liquid paraffin 5.0
Squalane 3.0
Isopropyl myristate 8.0
Polyoxyethylene (20) glyceryl monostearate 2.0
Propylparaben 0.1
[B component]
Testosterone-5α-reductase inhibitor of Example 1 5.0
Sorbitol 3.0
1,3-butylene glycol 5.0
Triethanolamine 1.5
Methylparaben 0.1
Purified water Amount of 100 parts [component C]
Titanium oxide 8.0
Talc 2.0
Kaolin 5.0
Bentonite 1.0
Coloring pigment appropriate amount [component D]
Fragrance 0.3
Component C was mixed and pulverized with a pulverizer. The component B was mixed, and the pulverized component C was added thereto and uniformly dispersed in a colloid mill. The components A and B and C dispersed uniformly were each heated to 80 ° C., and then the components A were added to the components B and C while stirring, and further homogenized with Hiscotron (5000 rpm) for 2 minutes. After cooling this to 50 degreeC, D component was added and stirred and mixed, and also it cooled to 30 degrees C or less, stirring, and obtained the cream foundation.

Formulation Example 22. Hair artic [component A] part ethanol 60.0
l-Menthol 0.5
Fragrance 0.1
Methylparaben 0.1
[B component]
Glycerin 2.0
1,3-butylene glycol 2.0
Testosterone-5α-reductase inhibitor of Example 3 10.0
Purified water in an amount of 100 parts The above A component and B component were each dissolved at room temperature, then the B component was added to the A component with stirring and dissolved to obtain a hair-tonic.

Formulation Example 23. Hair treatment [ingredient] part stearyltrimethylammonium chloride 6.0
Polyvinylpyrrolidone 4.0
Glycerin 1.0
Ethylparaben 0.1
Testosterone-5α-reductase inhibitor of Example 2 5.0
Purified water in a total amount of 100 parts The above ingredients were heated to 80 ° C and then mixed and stirred to obtain a hair treatment.
This product was also suitable as a hair pack.

Formulation Example 24. Hair shampoo [component A] part N-coconut oil fatty acid methyl taurine sodium 10.0
Polyoxyethylene (3) sodium alkyl ether sulfate 20.0
Lauryldimethylaminoacetic acid betaine 10.0
Palm oil fatty acid diethanolamide 4.0
Methylparaben 0.1
[B component]
Citric acid 0.1
Testosterone-5α-reductase inhibitor of Example 2 5.0
1,3-butylene glycol 2.0
Purified water Amount to be 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component, and stirring is continued to cool to room temperature to obtain a hair shampoo It was.

Formulation Example 25. Hair rinse [component A] Part Polyoxyethylene (10) hydrogenated castor oil 1.0
Distearyldimethylammonium chloride 1.5
Stearyltrimethylammonium chloride 2.0
Glyceryl 2-ethylhexanoate 1.0
Cetanol 3.2
Stearyl alcohol 1.0
Methylparaben 0.1
[B component]
Testosterone-5α-reductase inhibitor of Example 2 5.0
1,3-butylene glycol 5.0
Purified water Amount to be 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component and stirring is continued to cool to room temperature to obtain hair rinse It was.

Formulation Example 26. Body shampoo [component A] part N-lauroylmethylalanine sodium 25.0
Palm oil fatty acid potassium liquid (40%) 26.0
Palm oil fatty acid diethanolamide 3.0
Methylparaben 0.1
[B component]
Testosterone-5α-reductase inhibitor of Example 2 10.0
1,3-butylene glycol 2.0
Purified water Amount to be 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component and stirring is continued to cool to room temperature to obtain a body shampoo It was.

Formulation Example 27. Soap [component A] part hardened castor oil 26.0
Coconut oil 10.0
Olive oil 4.0
[B component]
Sodium hydroxide 6.0
Sugar 10.0
Glycerin 5.0
Testosterone-5α-reductase inhibitor of Example 6 0.5
Purified water Amount of 100 parts [component C]
Ethanol 20.0
Perfume Appropriate A component and B component were each heated to 80 ° C. and dissolved uniformly, and then B component was added to A component to saponify. This was cooled to 50 ° C. with stirring, and component C was added. This was poured into a mold and cooled, and then dried at room temperature for several days. A sufficiently dried product was taken out from the mold to obtain soap.

Formulation Example 28. Hair restorer [component A] part ethanol 60.0
Hinokitiol 0.5
Vitamin E 0.1
Polyoxyethylene (100) hydrogenated castor oil 1.0
Fragrance 0.1
[B component]
1,3-butylene glycol 2.0
Testosterone-5α-reductase inhibitor of Example 3 5.0
Purified water Total amount of 100 parts A component and B component are each heated to 50 ° C and dissolved uniformly, then B component is added to A component, mixed uniformly, cooled to room temperature and hair growth agent Obtained.

Claims (5)

A testosterone-5α-reductase inhibitor comprising an extract obtained from a marine flowering plant as an active ingredient. The testosterone-5α-reductase inhibitor according to claim 1, wherein the marine flowering plant is a plant of the genus Zosteraceae (Zostera sp.). The testosterone-5α-reductase inhibitor according to claim 2, wherein the plant of the genus Zostera sp. Is Zostera marina. A skin cosmetic containing the testosterone-5α-reductase inhibitor according to claim 1. A hair cosmetic comprising the testosterone-5α-reductase inhibitor according to claim 1.