JPH0578220A - 5alpha-reductase inhibitor and cosmetic composition - Google Patents

Abstract

PURPOSE:To provide a 5alpha-reeducates inhibitor and a cosmetic composition, showing a strong activity and free from a problem of safety. CONSTITUTION:A 5alpha-reductase inhibitor containing 0.05-0.3wt.% substance obtained by extracting leaves and/or stems of KAKOCHA (a kind of tea) with water or a hydrophilic organic solvent or a mixture solvent thereof and a cosmetic component containing 0.001-0.3wt.% of the above-mentioned substance. Effective for improving and preventing male alopecia, hypersteatosis, hirsutism, hidradentis suppurativa, prostatomegaly, prostatic cancer, etc., and for keeping cleanliness of the skin and the hair.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a 5α-reductase inhibitor containing an extract substance obtained from Chinese tea as an active ingredient and a cosmetic composition containing the same.

[0002]

2. Description of the Related Art Diseases such as androgenetic alopecia or hirsutism,
In diseases such as purulent sweating gland inflammation or prostate cancer, which are considered to be one of the causes of apocrine gland dysfunction,
The action of androgens is considered to be the causative factor or aggravation factor, and various antiandrogens are used for the treatment of these diseases. The action of this antiandrogen agent is as follows: (1) 5α-reductase inhibition that inhibits the reduction of the male hormone testosterone to the more active male hormone dihydrotestosterone by inhibiting 5α-reductase It is known to have an action and (2) a receptor binding inhibitory action that inhibits the produced dihydrotestosterone from binding to its receptor in target cells.

Conventionally, as anti-androgen agents, those using oxendron (JP-A-59-59606), chlormadinone acetate (JP-A-59-98010) and the like are known, but the plant component is 5α- Examples of use as a reductase inhibitor include tocopheryl quinone (JP-A-58-193689), solvent-extracted extract of crude drug (JP-A-60-146829) selected from the group consisting of Acacia yak, fennel and the like, heat of amachazul tea. Water extract (JP-A-62-116520), extract from walnut leaf and / or pericarp (JP-A-63-203625), extract obtained from a crude drug of any of cashew, mocca, salamander, and sardine It is known to use things.

[0004] However, it is generally pointed out that when the anti-androgen agent has a high 5α-reductase inhibitory activity, it has been pointed out that there are problems in safety such as side effects, and it is highly active and there is no problem in safety. At present, a reductase inhibitor is desired. On the other hand, as hair or skin cosmetics using extracts such as tea, flavanols (JP-A-59-51209), oolong tea extracts (JP-A-61-137807), and tea extracts (JP-A-61-137807). 61-28
0414), an extract of tea fruits (Japanese Patent Laid-Open No. 61-17140).
6), an extract of tea leaves (JP-A-63-280007, 2)
80009), condensed tannin (JP-A-62-5391)
7), the one containing the extract from the fermentation product of oolong tea and black tea is disclosed, but the example containing the extract from Hako tea is not disclosed.

[0005]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a 5α-reductase inhibitor and a cosmetic composition which have high activity and have no safety problems.

[0006]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that the extract of Chinese tea has a high 5α-reductase inhibitory action, and It came to completion. That is, the present invention is an invention of a 5α-reductase inhibitor containing a substance obtained by extracting leaves and / or stems of Chinese tea with water, a hydrophilic organic solvent or a mixed solvent thereof as an active ingredient.

Further, the present invention is an invention of a cosmetic composition containing a substance obtained by extracting leaves and / or stems of Chinese tea with water, a hydrophilic organic solvent or a mixed solvent thereof. The present invention will be described in detail below. The Hako tea used for extraction may be any of fermented tea, semi-fermented tea or non-fermented tea. As for the Hako tea used for extraction, any of leaves and stems can be used. It does not matter whether it is dried or undried, but it is preferable to use it after drying because the extraction effect is enhanced. In addition, at the time of extraction, crushing is preferable from the viewpoint of extraction efficiency.

As the extraction solvent, water, a hydrophilic organic solvent or a mixed solvent thereof is used. Examples of the hydrophilic organic solvent include methanol, ethanol, isopropyl alcohol, n-butanol, sec-butanol, te.
rt-Butanol, n-amyl alcohol, iso-amyl alcohol, sec-amyl alcohol, tert-amyl alcohol, and other alcohols, acetone, methyl ethyl ketone, methyl isobutyl ketone, and other ketones, ethyl ether, isopropyl ether, tetrahydrofuran, and other ethers Examples thereof include esters such as ethyl acetate, glycols such as ethylene glycol, diethylene glycol and polypropylene glycol, glycol ethers such as ethylene glycol monomethyl ether and diethylene glycol monomethyl ether, glycerin and a mixed solvent thereof, particularly water. Is preferred.

[0009] The extraction is usually carried out by immersing the scented tea in an extraction solvent, and may be at room temperature or under heat. Generally 1
It is 5 to 80 ° C, preferably 20 to 60 ° C. After extraction, the extraction residue is removed by filtration or centrifugation. The 5α-reductase inhibitor thus obtained is
Depending on the solvent used, the extraction solution may be used as it is, or may be used as a solid by concentrating it at an appropriate stage or drying it to dryness. If necessary, purification treatment such as decolorization can be carried out, and such treatment may be carried out at any stage.

The obtained extract substance is a dry solid powder having a brown appearance and is easily soluble in polar solvents such as ethanol and water. When the 5α-reductase inhibitor of the present invention is prepared using this substance, the amount of the substance in the composition is 0.0001 to
It is 2% by weight, preferably 0.01 to 1.0% by weight.

The 5α-reductase inhibitor of the present invention can be administered by various methods such as, for example, transdermal, oral, intravenous or rectal, and has a dosage form suitable for each, such as an ointment or a lotion. , Coating agent, alcoholic agent, aerosol agent,
It can be formulated into external powders, emulsions, suspensions, powders, granules, tablets, capsules, internal liquids, ampoules or suppositories. Such a preparation is prepared by dissolving, emulsifying or suspending the extracted substance as it is, or dissolving the extracted substance in a suitable pharmaceutically or pharmaceutically acceptable solvent for each dosage form,
And / or by mixing with a suitable additive, and further by mixing with a suitable base, it can be carried out by a conventional method. Suitable pharmaceutically and pharmaceutically acceptable solvents include purified water, ethanol, glycerin, propylene glycol and the like, and suitable pharmaceutically and pharmaceutically acceptable additives include lactose and glucose. , D-mannitol, starch, crystalline cellulose, calcium carbonate, kaolin, starch, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, gelatin powder, carboxymethyl cellulose, carboxymethyl cellulose calcium salt, magnesium stearate,
Talc, acetyl cellulose, sucrose, titanium oxide, benzoic acid, paraoxybenzoate, sodium dehydroacetate, gum arabic, tragacanth, methylcellulose, egg yolk, surfactant, simple syrup, citric acid, sodium monohydrogen phosphate, diphosphate Sodium hydrogen, sodium phosphate, sodium chloride, phenol, thimerosal and the like can be mentioned. Further, suitable pharmaceutically and pharmaceutically acceptable bases include cacao butter, lauric butter, cinnamon butter, witepsol, macro. Examples include gall, glycerin, glycerogelatin, methyl cellulose, carboxymethyl cellulose sodium salt and the like. In addition, colorants, corrigents, stabilizers and the like may be added as required.

The dose of the 5α-reductase inhibitor of the present invention is such that the amount of the active ingredient is 0.001 to 2 per day in an adult.
g, preferably 0.01 to 0.5 g, and more preferably 0.05 to 0.3 g. Also, this 5α-
When a reductase inhibitor is used in the cosmetic composition of the present invention, the amount of the substance in the composition is 0.0001 to 2% by weight as solid content, preferably 0.001 to 1.
It is 0% by weight. As the target cosmetic composition, cosmetics such as after-shave lotion, face lotion, lotion, face cream, hair cosmetics such as hair tonic, hair liquid, hair lotion, hair tonic, hair restorer, shampoo, rinse, treatment, etc. Can be mentioned.

[0013]

The extract substance obtained in the present invention has a high 5α
-It is a substance that has a high reductase inhibitory action and high safety, and has little coloration and odor. 5α-reductase inhibitors containing this as an active ingredient, androgenetic alopecia, hypersebum,
It is effective for the treatment and prevention of diseases associated with male hormones such as hirsutism, purulent sweating gland inflammation, prostatic hypertrophy, and prostate cancer. Further, the cosmetic composition containing this is effective for keeping the skin and hair clean and healthy.

The present invention will be described below with reference to examples, but these examples do not limit the scope of the present invention.

[0015]

EXAMPLES Example 1 Extraction of 5α-Reductase Inhibitors 100 g of crushed Chinese tea leaves were added to 1000 ml of 30% ethanol aqueous solution (dried Chinese tea / solvent = 1/10),
It was immersed at 60 ° C. After 3 hours, the extract was filtered, and ethanol was distilled off from the obtained filtrate using an evaporator. Lyophilization gave 20 g of the extract as a dry product. Yield 20%.

Example 2 5α-Reductase Inhibitory Action A supernatant fraction of a rat prostate homogenate was used as a 5α-reductase enzyme solution, and as a male hormone [ ³
H] Testosterone was used to extract the extract obtained in Example 1 and the extract of Gempi tea, Oolong tea, Kevin tea and assembly for comparison and 5α of oleanolic acid.
-The reductase inhibitory effect was investigated.

[ ³ H] Testosterone 20 μl / 2 μC
i, NADPH 1 mmol and 5α-reductase enzyme solution 2
Tris-HCl buffer containing 50 μl [50 mM Tris, 1.3 mM EDTA, 1 mM DTT (dithiothreitol), 10 mM Na ₂ MoO ₄ , 10% glycerol, 1N HC
l, water, pH 7.4] to dissolve the extracted substance to a predetermined concentration to make a volume of 500 μl,
Incubated for hours.

1 or 2 ml of Folch's solution (chloroform /
Extraction treatment was performed with methanol = 2/1) and thin layer chromatography was performed using chloroform / methanol = 99/1 as a developing solvent to separate testosterone and dihydrotestosterone. RI measurement and radioactivity measurement were carried out with a chromatographic scanner to calculate the conversion rate of testosterone to dihydrotestosterone. The 5α-reductase inhibition rate was calculated by the following formula, and the results are summarized in Table 1.

Inhibition rate (%) = (conversion rate of control−
Conversion rate of sample with extraction substance added / conversion rate of control) x 100

Table 1 ───────────────────────────── Extracted substance concentration (%) Inhibition rate (%) ──── ───────────────────────── Hua Tea 0.004-7.6 0.02 15.9 0.1 93.3 Genpi Tea 0 0.004 -10.9 0.02 -9.4 0.1 35.6 oolong tea 0.004 -1.5 0.02 -49.5 0.1 -49.5 oleanolic acid 0.004 -1.3 0.01 0.3 Kevin tea 0.004-2.7 0.02-3.5 0.1 24.7 assembly 0.004 20.6 0.02 46.6 0.1 48.5 ---- ────────────────────────── Extracted substances from Hako-kocha have a concentration of 0.0
It can be seen that 2% and 0.1% have a high 5α-reductase inhibitory action.

Example 3 Sebum Inhibitory Action The extract substance of Example 1 dissolved in a 50% aqueous ethanol solution to a concentration of 1% and, for comparison, the oolong tea and the assembly extract were forehead parts of three hamsters each. Was applied once a day to a specific part of the and was continued for 1 week. Separately, as a control, a 50% aqueous ethanol solution containing no extraction substance was similarly applied.

After continuing for 1 week, the amount of sebum in the forehead of the hamster secreted in 2 hours was measured using a sebum meter (SKICOS301 manufactured by Amic Group). The sebum secretion rate was calculated by the following formula, and the results are summarized in Table 2. Sebum secretion rate (%) = (sebum amount / control sebum amount)
× 100 Evaluation: Sebum secretion rate 〜70% ・ ・ ・ ・ Significant effect 70〜90% ・ ・ ・ Effective 90% 〜 ・ ・ ・ Ineffective

Table 2 ────────────────────────── Extracted substance Sebum secretion rate (%) Evaluation ────────── ──────────────── Hanako tea 71 Effective effect 86 Effective 86 Effective Oolong tea 120 Invalid 101 Invalid 103 Invalid Assembly 94 Invalid 93 Invalid 102 Invalid ────────── ──────────────── When applied with an extract from Hako tea, it has a lower sebum secretion rate than other products and may have a high sebum control effect. Recognize.

Example 4 Hair Growth Agent Pentadecanoic Acid Glyceride 3.0% by Weight (Monoglyceride: Diglyceride) Tocopherol Acetate 0.1 Chinese Tea (Leaf) Extract 0.1 Propyl Linoleate 3.0 Hinokitiol 0.05 Sorbitan Monolaurate 5.0 isopropylmethylphenol 0.1 perfume 0.4 99.5% ethanol Balance total 100.0

Example 5 Hair Tonic Ethanol extract of ancient tea (5% extract) 0.01% by weight Ethyl oleate 1.0 El-menthol 0.1 Benzyl nicotinate 0.003 Piroctone oamine 0.03 POE (40) hydrogenated castor oil 2.0 perfume 0.3 95% ethanol 40.0 purified water Balance total 100.0

Example 6 Hair Liquid Hana-ko Tea Polyethylene Glycol 0.01% by Weight Extract (Extracted Material 10%) Methyl Palmitoleate 2.0 Polyoxypropylene butyl ether 20.0 Lanolin 1.0 Perfume 1.0 Preservative, ultraviolet inhibitor qs 95% ethanol 55.0 purified water Balance total 100.0

Example 7 Set Lotion Polyvinylpyrrolidone 3.0% by weight Propylene glycol 2.0 Extract of Chinese tea (stem) 0.07 Ethyl myristoleate 3.0 Ethyl alcohol 10.0 Fragrance Purified water Residue Total 100.0

[0028] Example 8 Face Lotion sulfo carbolic Zinc 1.0 wt% Hana old tea (leaf) extract 0.3 Aloe ECW 0.5 palmitoleic acid propyl 2.0 Perfume 0.5 Ethyl alcohol Balance Total 100.0

Example 9 Shampoo Hakuko tea extract aqueous solution (extracted substance 1%) 1.0% by weight sodium lauryl ether sulfate 5.0 sodium α-olefinsulfonate 10.0 lauryl sulfate triethanolamine 4.0 cationization cellulose 1.0 octyl oleate 1.0 purified water Balance total 100.0

Example 10 Rinse Stearyltrimethylammonium chloride 1.5% by weight Stearyldimethylammonium chloride 0.5 Cetostearyl alcohol 1.5 Hakocha tea ethylene glycol 3.0 Extract liquid (extracted substance 0.3%) Liquid paraffin 1 .0 petroselinic acid ethyl 1.0 purified water Balance total 100.0

Example 11 Blow treatment Stearyltrimethylammonium chloride 0.3% by weight Chinese tea 50% Ethanol extract (extracted substance 3%) 0.5 Methyl linolenate 3.0 N-Lauroylglutamic acid 1.0 Propylene glycol 3 .0 ethanol 10.0 purified water Balance total 100.0

Example 12 Treatment Hua Tea (leaf) extract 0.2% by weight Isostearic acid 0.5 Stearyl trimethyl ammonium chloride 1.0 Ethyl ricinoleate 1.0 Propylene glycol 5.0 Flavin adenine dinucleotide 0.2 purified water Balance total 100.0

Example 13 Lotion Lotion Green tea water extract (extracted substance 1%) 3.0% by weight Glycerin 5.0 Ethyl alcohol 10.0 Aloe cape liquid 0.5 Ethyl undecylenate 0.5 Irgasan DP-300000 .1 Purified water 78.8 Total 100.0

Example 14 Spray antiperspirant Hydroxyaluminum chloride 1.0% by weight Hakukocha ethanol extract (extracted substance 1%) 0.7 Talc 1.0 Ethyl oleate 1.0 SiO ₂ 0.2 Myristic acid Isopropyl 1.0 Carnitine heptadecanoic acid ester 0.8 Cyclic silicone 1.0 Ethyl alcohol 9.2 LPG 84.75 Total 100.0

Example 15 After shaving lotion Ethyl alcohol 10.0% by weight Dipropylene glycol 1.0 Ethyl undecylenate 0.5 Zinc sulfocarbonate 0.2 Hako tea extract 0.2 Perfume proper amount Salicylic acid 0.5 Purification water Balance total 100.0

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location A61K 35/78 AEE C 7180-4C

Claims (2)

[Claims] 1. A 5α-reductase inhibitor containing a substance obtained by extracting leaves and / or stems of Chinese tea with water, a hydrophilic organic solvent or a mixed solvent thereof as an active ingredient. 2. A cosmetic composition containing a substance obtained by extracting the leaves and / or stems of Chinese tea with water, a hydrophilic organic solvent or a mixed solvent thereof.