JP2008088076A - TESTOSTERONE 5alpha-REDUCTASE ACTIVITY INHIBITOR, ANDROGEN RECEPTOR ANTAGONIST, USE THEREOF, AND METHOD FOR INHIBITING ANDROGEN ACTIVITY EXPRESSION - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new testosterone 5α-reductase activity inhibitor, to provide a new androgen receptor antagonist, to provide a hair tonic, to provide a skin care preparation for preventing/improving acne, to provide a skin care preparation for inhibiting sebum secretion, and to provide a method for inhibiting androgen activity expression. <P>SOLUTION: Provided are the testosterone 5α-reductase activity inhibitor containing a Chloranthus japonicus extract as an active ingredient, the androgen receptor antagonist containing the Chloranthus japonicus extract as an active ingredient, the hair tonic containing their agents, the skin care preparation for preventing/improving acne, and the skin care preparation for inhibiting sebum secretion containing the agents. A method for inhibiting androgen activity expression comprising supplying the Chloranthus japonicus extract is also provided. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a testosterone 5α-reductase activity inhibitor and an androgen receptor antagonist that are useful as active ingredients for external preparations for skin such as cosmetics. The present invention also relates to a hair nourishing agent, a skin external preparation for preventing and / or improving acne, a skin external preparation for suppressing sebum secretion, and a method for suppressing the expression of androgen activity.

  Conventionally, for the purpose of imparting prescribed medicinal effects to skin external preparations such as emulsions, creams, lotions, packs, cleaning agents, dispersions, ointments, solutions, aerosols, patches, poultices, liniments, etc. Various medicinal ingredients have been added. In recent years, various causes of skin troubles have been elucidated, and along with this, consumer needs for external preparations for skin, particularly cosmetics, are being subdivided. Androgen is an important hormone for the body, but when it acts excessively, it is known that it induces various unfavorable symptoms on the scalp and skin such as androgenetic alopecia, seborrhea and acne. It has been. It is known that excessive expression of androgen activity can be suppressed by testosterone 5α-reductase activity inhibitory action or by androgen receptor antagonism. Therefore, it is desired to provide an agent capable of suppressing excessive androgen activity expression by testosterone 5α-reductase activity inhibitory action and androgen receptor antagonistic action.

On the other hand, since the safety to the skin is also important as an active ingredient to be blended in the external preparation for skin, various plant extracts that are agents derived from natural products have been proposed as active ingredients for external preparations for skin. Yes. For example, a moisturizing agent composed of a human lizard extract has been proposed (Patent Document 1).
Japanese Patent No. 3696862

An object of the present invention is to provide a novel testosterone 5α-reductase activity inhibitor and an androgen receptor antagonist that are highly safe for the skin and are useful as an active ingredient of an external preparation for skin.
The present invention also provides a hair nourishing agent having an excellent hair nourishing effect, an anti-acne anti-acne effect and / or an improved skin external agent for improving acne, and an external skin for skin secretion inhibiting having an excellent sebum secretion inhibiting effect. It is an object to provide an agent.
Another object of the present invention is to provide a novel method for suppressing the expression of androgenic activity.

In order to solve the above-mentioned problems, the present invention provides a testosterone 5α-reductase activity inhibitor containing human lysizuka extract as an active ingredient, and an androgen receptor antagonist containing human lysizuka extract as an active ingredient.
From another point of view, according to the present invention, a hair nourishing agent containing human lizard extract as an active ingredient, a skin external preparation for preventing and / or improving acne containing human lizard extract as an active ingredient, and human lizard extract as an active ingredient A method for suppressing the expression of androgenic activity by supplying a skin external preparation for suppressing sebum secretion and a human lysizuka extract, and at least by an inhibitory action on testosterone 5α-reductase activity and / or by an androgen receptor antagonistic action And said method of suppressing the expression of androgenic activity.

  According to the present invention, a novel testosterone 5α-reductase activity inhibitor and androgen receptor antagonist can be provided. Moreover, according to this invention, the novel hair nourishing agent, the skin external preparation excellent in the acne prevention effect / improvement effect, and the skin external preparation excellent in the sebum secretion suppression effect can be provided. Moreover, according to the present invention, a novel method for suppressing the expression of androgenic activity can be provided.

Hereinafter, the present invention will be described in detail. In the present specification, “to” means a range including numerical values before and after.
The testosterone 5α-reductase activity inhibitor and the androgen receptor antagonist of the present invention contain, as an active ingredient, an extract of Chloranthus japonicus (scientific name: Chloranthus japonicus). There is no restriction | limiting about an extraction site | part, and the extract of any parts, such as a root, stem, a leaf, an inflorescence, a fruit, and a seed of a human lizardfish, may be sufficient as the human lizard extract used for this invention. In addition, the testosterone 5α-reductase activity inhibitor and androgen receptor antagonist of the present invention may be mixed with extracts obtained from two or more places of human lysizuka, or extracted from two or more parts with different solvents. A mixture of two or more extracts may be used.

  The human lizard extract is obtained by extracting one or two or more places such as roots, stems, leaves, inflorescences, fruits, seeds, etc. of human lizards with an appropriate solvent and distilling off the solvent. These portions may be subjected to an appropriate treatment such as drying, shredding, pressing, or fermentation, followed by an extraction treatment. Extraction can be carried out by immersing human lizard in a solvent at a low temperature or under warming for a predetermined time. The extraction solvent is not particularly limited, but water or lower monohydric alcohols such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; ketones such as acetone; ethyl ether and the like 1 type or 2 types or more of organic solvents, such as these ethers; or esters, such as ethyl acetate; and the mixed solvent of these and water can be used.

  The human squirrel extract may be used as it is in a skin external preparation, or may be used after being left to stand for an appropriate period and aged. If necessary, it can be used after further purification treatment such as filtration, deodorization and decolorization with an ion exchange resin or the like within a range not affecting the effect. Further, only a fraction having a high activity can be used by using a separation means such as liquid chromatography.

  Examples of preferred methods for preparing the human lizard extract include human lizards, alcoholic solvents such as hydrous or non-hydrated ethyl alcohol, polyhydric alcohol solvents such as hydrous or non-hydrated 1,3-butylene glycol, or water. The mixture is filtered at room temperature or warmed for 1 to 5 days, filtered, and the filtrate obtained is left to mature for about one week, and the filtrate is filtered again.

Examples of the components in the extract include flavonoid glycosides, phenols, amino acids, triterpenes and the like. The higher the content of the alcohol solvent or polyhydric alcohol solvent in the extraction solvent, the higher the triterpene content.
The human lysizuka extract used for the testosterone 5α-reductase activity inhibitor or the androgen receptor antagonist of the present invention preferably has a mixed solvent of water and monohydric alcohol, and a mixed solvent of water and ethyl alcohol. More preferably, it is a mixed solvent of water and ethyl alcohol in which the mixing ratio of ethyl alcohol is 50 volume% (hereinafter referred to as “vol%”) or more.

  The human lizard extract can be used as an extract, dried by spray drying or the like, or in a powder form, or a dry solid or powder mixed with an appropriate solvent according to the intended use. That is, it may be used as an active ingredient of a testosterone 5α-reductase activity inhibitor or an androgen receptor antagonist in any form such as liquid, paste or gel.

Here, the relationship between testosterone 5α-reductase activity inhibitory action and androgen receptor antagonistic action, hair restoration effect, acne prevention and / or improvement effect, and sebum secretion inhibitory effect will be described.
Many steroid hormones bind to receptors in the molecular form secreted from the production organ and exert their actions. For example, male hormones collectively called androgens, for example, testosterone enters the cells of the target organ and becomes testosterone 5α. -It is reduced to 5α-dihydrotestosterone (5α-DHT) by reductase and then binds to a receptor to exert an action as an androgen. The androgen is an important hormone for the living body, but when it acts excessively, it induces various unfavorable symptoms on the scalp and skin such as androgenetic alopecia, seborrhea and acne. Excess androgen action is suppressed by inhibiting the action of testosterone 5α-reductase which reduces testosterone to 5α-DHT or by inhibiting the binding of 5α-DHT generated from testosterone to the receptor. be able to. That is, by inhibiting the activity of testosterone 5α-reductase or inhibiting the binding of 5α-DHT to the receptor, excellent hair restoration effect, sebum secretion suppression effect, and acne prevention / An improvement effect can be expected.

  The testosterone 5α-reductase activity inhibitor and androgen receptor antagonist of the present invention can be used for various applications. Since the safety to the skin is good, it is preferably blended into the external preparation for skin. In addition, the testosterone 5α-reductase activity inhibitor and the androgen receptor antagonist of the present invention can be added to foods (including beverages). Although it does not restrict | limit especially as said foodstuff, Specifically, a salmon, chewing gum, a drink etc. are mentioned, for example.

Next, the hair nourishing agent, the acne prevention / improvement skin external preparation of the present invention, and the skin external preparation for suppressing sebum secretion (hereinafter collectively referred to as “skin external preparation etc.”) will be described in detail.
The topical skin preparation of the present invention contains, for example, a human lizard extract that is a testosterone 5α-reductase activity inhibitor or an androgen receptor antagonist of the present invention as an active ingredient. Although there is no restriction | limiting in particular about the compounding quantity of the said agent, The said human lizard extract is 0.00005-1.5 mass% as solid content (henceforth only "" % ”), And more preferably 0.0005 to 1.5%. If it is in this range, the component can be stably blended, and high testosterone 5α-reductase activity inhibitory action and androgen receptor antagonistic action are brought about, and based on this, nourishing effect, acne prevention / An improvement effect or a sebum secretion suppression effect can be exhibited. In addition, when the extract is used, the concentration of the extract is not limited as long as the content of the human squirrel extract as a solute is within the above range.

  The form of the external preparation for skin according to the present invention is not particularly limited. Any form of cosmetics such as pills and liniments may be used as external medicines.

  In addition to the radical scavenger, the skin external preparation of the present invention includes various components that are usually used in cosmetics, quasi-drugs, external medicines, ie, water, alcohols, oils, surfactants, Viscosity, powder, chelating agent, pH adjuster, UV absorber, extracts from animals and plants / microorganisms, various medicinal agents such as moisturizers, whitening agents, anti-inflammatory agents, cell activators, fragrances, etc. As long as the effect is not impaired, it can be added as appropriate.

  The present invention also relates to a method for suppressing the expression of androgenic activity by supplying a human squirrel extract. The human lysizuka extract provides at least a testosterone 5α-reductase activity inhibitory action and / or an androgen receptor antagonism, thereby suppressing the expression of androgen activity. For example, it may be applied to the surface of the skin (including the scalp) and used for hair restoration, for preventing / improving acne, or for suppressing sebum secretion. In addition, it can be used for the purpose of improving the appearance of the skin, that is, cosmetic purposes, by preventing / improving acne or suppressing sebum secretion.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited to the following examples.
[Example 1: Production of 80% hydrous ethyl alcohol extract of human lizards]
150 g of 80% hydrous ethyl alcohol (the ratio of ethyl alcohol is 80 vol%) is added to 10 g of human squirrel grass, extracted at room temperature or heated for one day, filtered, and the solvent in the obtained filtrate is filtered. Distilled to dryness, an 80 vol% water-containing ethyl alcohol extract (yield 0.8 g) of human lizards as a solid content was obtained.

[Example 2: Example of production of human lizardka 50 vol% hydrous ethyl alcohol extract]
150 g of 50 vol% hydrous ethyl alcohol (the ratio of ethyl alcohol is 50 vol%) is added to 10 g of human squirrel grass, extracted at room temperature or heated for one day, filtered, and the solvent in the obtained filtrate is filtered. Distilled to dryness to obtain a 50 vol% water-containing ethyl alcohol extract (yield: 0.75 g) of human lizards as a solid content.

[Example 3: Production example of purified water extract of Hitorizuka]
150 mL of purified water is added to 10 g of the whole plant of human lizard, and after extraction for one day at room temperature or warming, the mixture is filtered, and the solvent in the obtained filtrate is evaporated to dryness to obtain a solid content. A purified human water extract (yield 0.73 g) was obtained.

[Example 4: Evaluation of testosterone 5α-reductase activity inhibitory effect]
A V-bottom tube with a lid was mixed with 20 μL of 4.2 mg / mL testosterone prepared with propylene glycol and 825 μL of 5 mmol / mL Tris-hydrochloric acid buffer (pH = 7.13) containing 1 mg / mL NADPH. To this, 80 μL of a test sample prepared with ethyl alcohol, 50 vol% ethyl alcohol or purified water and 75 μL of S-9 were added and mixed again. After reacting at 37 ° C. for 30 minutes, 1 mL of methylene chloride was added to stop the reaction. did. This was separated by centrifugation (1600 × g, 10 minutes), and the methylene chloride layer was analyzed by gas chromatography under the following conditions. A blank test was conducted in the same manner.
Gas chromatographic analysis was performed in the same manner for methylene chloride solutions of 3α-androstanediol, dihydrotestosterone (DHT) and testosterone standard products in advance, and the amount of compounds per peak area was calculated from the exact amount and peak area of these three compounds. The concentrations per peak area of 3α-androstanediol, dihydrotestosterone (DHT) and testosterone after the reaction with S-9 were determined (Formula 1). Then, according to Formula 2, the conversion rate of the test sample was calculated | required. Based on this conversion rate, the testosterone 5α-reductase activity inhibitory action was determined according to Equation 3.
In addition, the aqueous solution (a density | concentration is 3000 microgram / mL) of the human lizards extract was used as each test sample.
(Formula 1)
Concentration (%) = peak area of test sample × standard product concentration / standard product peak area (Formula 2)
Conversion rate (%) = (A + B) / (A + B + C)
A: concentration of 3α-androstanediol B: concentration of dihydrotestosterone (DHT) C: concentration of testosterone (formula 3)
Testosterone 5α-reductase activity inhibition rate (%) = (1−E / D) × 100
D: Conversion rate in blank test E: Conversion rate in addition of test sample

Conditions for gas chromatography Equipment used: Shimadzu GC-7A
Column: DB-1701 (0.53 mmφ × 30 m, film thickness 1.0 μm)
Column / injection temperature: 240 ° C./300° C.
Detector: FID
Carrier gas: Nitrogen gas

[Example 5: Evaluation of androgen receptor antagonism]
SC-3 cells cloned from mouse spontaneous breast cancer (Shionogi cancer; SC115) were cultured using 2% DCC-FBS and ^10-8 mol / L testosterone-containing MEM (MEM / 2), and then treated with trypsin. Was recovered. The collected cells were diluted to a concentration of 1.0 × 10 ⁵ cells / mL with 2% DCC-FBS-containing MEM (MEM / 2), seeded at 100 μL per well in a 96-well plate, and cultured overnight. After completion of the culture, the medium was removed, 100 μL of a test sample dissolved in 0.5% BSA-containing Ham F12 + MEM (HMB) containing 10 ⁻⁹ mol / L DHT was added, and cultured for 48 hours. Thereafter, 100 μL of MTT dissolved in MEM / 2 containing 2% DCC-FBS at a final concentration of 0.4 mg / mL was added to each well. After culturing for 2 hours, blue formazan produced in the cells was extracted with 200 μL of 2-propanol. After extraction, the absorbance at a wavelength of 570 nm was measured. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used as the amount of blue formazan produced. As a blank test, a cell cultured with HMB alone was used as a positive control, and a cell cultured with HMB containing only 10 ⁻⁹ mol / L DHT was used as a positive control, and the test was conducted in the same manner to correct it.
The calculation method of androgen receptor antagonism is as follows.
Androgen receptor antagonist ratio (%) = {1- (C−D) / (A−B)} × 100
A: Absorbance at 570-650 nm without addition of DHT and no test sample B: Absorbance at 570-650 nm without addition of DHT and no test sample C: Absorbance at 570-650 nm with addition of DHT and addition of test sample D: Absorbance at 570 to 650 nm without addition of DHT and addition of test sample As each test sample, an aqueous solution (concentration: 50 μg / mL) of human lysizuka extract was used.

[Example 6: lotion]
A lotion was prepared by the composition shown in Table 3 and the following production method, and the effect of preventing the acne of the human lizard extract was examined. The results are also shown in Table 3.

(Composition and results)

(Manufacturing method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (11) are mixed and dissolved.
C. A and B were mixed and uniformed to obtain a skin lotion.

<Acne prevention effect judgment test>
For the above-mentioned lotions of the present invention and comparative products, acne prevention and improvement effects were determined by the following methods. The test subjects were women in their 10s and 20s who suffered from acne, and 20 people in each group applied the test product to the facial cheek twice a day (morning and evening) and conducted a continuous test for 4 weeks. After the continuous test, the acne prevention effect was evaluated according to the following criteria based on the visual perception by the subject himself, and the value obtained by dividing the number of people who evaluated “effective” or higher by the number of subjects (20 people) was obtained.

<Evaluation criteria>
Remarkable: The number, size and inflammation of acne were significantly reduced and symptoms were improved.
Effective: Reduced the number, size and inflammation of acne and reduced symptoms.
Slightly effective: tended to reduce the number, size and inflammation of acne.
No effect: did not reduce or exacerbate the number, size and inflammation of acne.

  From the results of Table 3, the lotions of the present invention products 1 and 2 formulated with 80% ethyl alcohol extract of human lizards and 50% ethyl alcohol extract of human lizards exhibit the effect of preventing acne by applying these to the skin. It became clear to get.

Hereinafter, examples of blending into cosmetics will be shown, but not limited to these prescriptions.
[Example 7: Cleansing cream]
(Ingredient) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 3.0
(3) Lipophilic glyceryl monostearate 2.0
(4) Beeswax 1.5
(5) Vaseline 6.0
(6) Liquid paraffin 40.0
(7) Dimethylpolysiloxane (100CS) 0.5
(8) Sorbitan sesquioleate 1.0
(9) Preservative appropriate amount (10) Triethanolamine 1.0
(11) Propylene glycol 10.0
(12) Polyethylene glycol 20000 0.5
(13) Carboxyvinyl polymer 0.05
(14) Purified water Residual amount (15) Hitorizuzka 80vol% hydrous ethyl alcohol extract * 1 0.5
(16) Peppermint extract * 2 0.5
(17) Ononis extract * 3 0.5
(18) Fragrance Appropriate amount * 1: The extract produced in Example 1 dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. Made (Manufacturing method)
A. Ingredients (1) to (9) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (10) to (14) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (15) to (18) were added and mixed to obtain a cleansing cream.
The obtained cleansing cream was a mild cleansing cream that spreads lightly and has good makeup removal, prevents excessive sebum secretion and acne, and maintains healthy skin.

[Example 8: Face wash]
(Ingredient) (%)
(1) Lauric acid 5.0
(2) Myristic acid 18.5
(3) Stearic acid 6.0
(4) Glycerin 12.0
(5) Polyethylene glycol 1500 5.0
(6) Potassium hydroxide 6.5
(7) Purified water remaining amount (8) Palm oil fatty acid diethanolamide 5.0
(9) Palm oil fatty acid methyl taurine sodium 1.8
(10) Polyoxyethylene (7.5E.O.) lauryl ether 2.0
(11) Ethylene glycol distearate 1.0
(12) Hydroxypropyl methylcellulose 1% aqueous solution 5.0
(13) Hitori-Sizuka 50vol% hydrous ethyl alcohol extract * 1 0.5
(14) Tencha extract * 2 0.5
(15) Tea extract * 3 0.5
(16) Fragrance Appropriate amount * 1: What was obtained by dissolving the extract produced in Example 2 in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 2: Koei Kogyo Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. Company (production method)
A. Components (1) to (7) are dissolved by heating.
B. Components (8) to (11) are dissolved by heating.
C. Add B to A and mix.
D. After cooling C, components (12) to (16) are added and mixed to obtain a face wash.
The obtained cleansing cream and facial cleanser had a fine and rich foaming and a refreshing feeling of use, and it was a facial cleanser that prevented excessive sebum secretion and acne and maintained healthy skin. .

[Example 9: Lotion 1]
(Ingredient) (%)
(1) Citric acid 0.05
(2) Sodium citrate 0.2
(3) Sodium pyrrolidonecarboxylate (50%) solution * 1 0.5
(4) Glycerin 3.0
(5) 1,3-butylene glycol 8.0
(6) L-ascorbic acid 2-glucoside * 2 2.0
(7) Sodium hydroxide 0.25
(8) Hiritishika purified water extract * 3 1.0
(9) Rosemary extract * 4 1.0
(10) Peach extract * 5 1.0
(11) Purified water remaining amount (12) Ethyl alcohol 10.0
(13) Perfume Appropriate amount (14) Preservative Appropriate amount (15) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
* 1: Ajinomoto Co., Inc. * 2: Hayashibara Biochemical Laboratories Co., Ltd. * 3: The extract produced in Example 3 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1%. * 4 : Made by Maruzen Pharmaceutical * 5: Made by Maruzen Pharmaceutical (Manufacturing method)
A. Components (1) to (11) are mixed and dissolved.
B. Components (12) to (15) are mixed and dissolved.
C. B was added to A and mixed to obtain a skin lotion.
The obtained lotion 1 had a fresh and refreshing feeling of use, and was a lotion that suppressed excessive sebum secretion and acne, kept the skin fresh and smoothed the skin.

[Example 10: Lotion 2]
(Ingredient) (%)
(1) Meadow home oil 0.1
(2) Jojoba oil 0.05
(3) Perfume appropriate amount (4) preservative appropriate amount (5) polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(6) Isostearic acid polyoxyethylene hydrogenated castor oil (50 EO) 1.0
(7) Ethyl alcohol 8.0
(8) Glycerin 5.0
(9) 1,3-butylene glycol 5.0
(10) Polyethylene glycol 1500 0.1
(11) Hitorishizuka 80vol% hydrous ethyl alcohol extract * 1 1.0
(12) Dipotassium glycyrrhizinate * 2 0.5
(13) Yokuinin extract * 3 0.5
(14) Remaining amount of purified water * 1: The extract produced in Example 1 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1%. * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Made by Pharmaceutical Company (Manufacturing method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (14) are mixed and dissolved.
C. A is added to B and mixed to obtain a skin lotion.
The obtained lotion 2 had a fresh and mellow feeling of use, and was a lotion that suppressed excessive sebum secretion and acne, kept the skin fresh and smoothed the skin.

[Example 11: Lotion 3]
(Ingredient) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.08
(2) Squalane 0.02
(3) Sorbitan sesquioleate 0.05
(4) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.05
(5) Polyoxyethylene (8E.O.) alkylene (12-15)
Ether phosphoric acid 0.1
(6) Preservative appropriate amount (7) perfume appropriate amount (8) ethyl alcohol 8.0
(9) Dipropylene glycol 8.0
(10) Glycerin 4.0
(11) Hitorishizuka 50 vol% hydrous ethyl alcohol extract * 1 0.5
(12) Sodium hyaluronate 1% aqueous solution * 2 10.0
(13) Oat extract * 3 0.5
(14) Purified water remaining amount * 1: What was obtained by dissolving the extract produced in Example 2 in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 2: manufactured by Kibun Food Chemifa * 3: Made by Maruzen Pharmaceutical Co., Ltd.
A. Components (1) to (8) are mixed and dissolved.
B. Components (9) to (14) are mixed and dissolved.
C. A is added to B and emulsified to obtain a skin lotion.
The obtained lotion 3 had a clean and light feeling of use, and was a lotion that suppressed excessive sebum secretion and acne, kept the skin fresh and smoothed the skin.

[Example 12: Latex]
(Ingredient) (%)
(1) Stearic acid 1.0
(2) Cetanol 0.5
(3) Lipophilic glyceryl monostearate 0.5
(4) Liquid paraffin 2.0
(5) Squalane 3.0
(6) Jojoba oil 3.0
(7) Cetyl palmitate 0.2
(8) Preservative appropriate amount (9) Sorbitan monostearate 0.3
(10) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(11) Stearyl glycyrrhetinate * 1 0.2
(12) Triethanolamine 0.5
(13) 1,3-butylene glycol 15.0
(14) Glycerin 3.0
(15) Polyethylene glycol 6000 0.5
(16) Purified water remaining amount (17) 1% solution of carboxyvinyl polymer 8.0
(18) Human squirrel 80 vol% hydrous ethyl alcohol extract * 2 0.5
(19) Hermanus extract * 3 0.5
(20) Carrot extract * 4 0.5
(21) Fragrance Appropriate amount * 1: Made by Maruzen Pharmaceutical Co., Ltd. * 2: The extract produced in Example 1 dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 3: Maruzen Pharmaceutical Co., Ltd. * 4: manufactured by Maruzen Pharmaceutical Co., Ltd.
A. Components (1) to (11) are dissolved by heating and maintained at 70 ° C.
B. Components (12) to (16) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and component (17) is further added and mixed.
D. C is cooled, and components (18) to (21) are added and mixed to obtain an emulsion.
The obtained emulsion has a smooth and mellow feeling, prevents excessive sebum secretion and prevents acne, gives the skin a moisturizing and moderate emollient feeling, and softens the skin. It was.

[Example 13: Cream]
(Ingredient) (%)
(1) Stearic acid 2.5
(2) Cetanol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Vaseline 2.0
(5) Dipentaerythritol fatty acid ester * 1 2.0
(6) Isotridecyl myristate 5.0
(7) Liquid paraffin 8.0
(8) Squalane 5.0
(9) Beeswax 1.0
(10) Cetyl palmitate 2.0
(11) Sorbitan sesquioleate 0.5
(12) Polyoxyethylene monooleate (20E.O.)
Sorbitan 1.5
(13) Preservative appropriate amount (14) Triethanolamine 1.2
(15) 1,3-butylene glycol 8.0
(16) Glycerin 2.0
(17) Polyethylene glycol 20000 0.5
(18) Purified water Remaining amount (19) Carboxyvinyl polymer 1% aqueous solution 10.0
(20) Salicylic acid * 2 0.2
(21) Human squirrel 50 vol% hydrous ethyl alcohol extract * 3 3.0
(22) Sodium acetylglutamate * 4 0.5
(23) Licorice extract * 5 0.5
(24) Assembly extract * 6 0.5
(25) Perfume appropriate amount * 1: Cosmol 168AR (Nisshin Oillio Group)
* 2: Wako Pure Chemical Industries, Ltd. * 3: The extract produced in Example 2 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1%. * 4: Kyowa Hakko Kogyo * 5 : Made by Maruzen Pharmaceutical * 6: Made by Maruzen Pharmaceutical (Manufacturing method)
A. Ingredients (1) to (13) are dissolved by heating and maintained at 70 ° C.
B. Ingredients (14) to (18) are dissolved by heating and maintained at 70 ° C.
C. B is added to A to emulsify, and component (19) is further added and mixed.
D. C is cooled, components (20) to (25) are added and mixed to obtain a cream.
The obtained cream had a smooth and rich feeling of use, was a cream that suppressed excessive sebum secretion and acne, imparted a high emollient feeling to the skin, and softened the skin.

[Example 14: Cosmetic liquid]
(Ingredient) (%)
(1) Glyceryl tri-2-ethylhexanoate 0.1
(2) Meadow Home Oil 0.05
(3) Jojoba oil 0.05
(4) Stearyl glycyrrhetinate * 1 0.5
(5) Tocopherol acetate * 2 0.1
(6) Preservative appropriate amount (7) perfume appropriate amount (8) polyoxyethylene monooleate (20E.O.)
Sorbitan 0.5
(9) Polyoxyethylene hydrogenated isostearate castor oil (50 EO) 1.5
(10) Ethyl alcohol 5.0
(11) Glycerin 4.0
(12) Dipropylene glycol 8.0
(13) 1,3-butylene glycol 8.0
(14) Sodium lactate 0.5
(15) Sodium pyrrolidonecarboxylate (50%) solution * 3 0.5
(16) Hydroxyethyl cellulose 0.08
(17) Sodium alginate 0.05
(18) Human squirrel 80 vol% hydrous ethyl alcohol extract * 4 5.0
(19) Hop extract * 5 0.5
(20) Warmoko extract * 6 0.5
(21) Purified water remaining amount * 1: Maruzen Pharmaceutical Co., Ltd. * 2: Eisai Co., Ltd. * 3: Ajinomoto Co., Inc. * 4: 50 vol% water containing 1, so that the content of the extract produced in Example 1 is 1% Dissolved in 3-butylene glycol * 5: manufactured by Maruzen Pharmaceutical Co., Ltd. * 6: manufactured by Maruzen Pharmaceutical Co., Ltd. (production method)
A. Components (1) to (9) are mixed and dissolved.
B. Components (10) to (21) are mixed and dissolved.
C. A is added to B and mixed to obtain a serum.
The resulting serum has a mellow and mild feel, prevents excessive sebum secretion and prevents acne, gives the skin a high moisturizing and emollient feel, and makes the skin fresh and soft. Met.

[Example 15: Pack (Peel-off type)]
(Ingredient) (%)
(1) Polyvinyl alcohol 12.0
(2) Methylcellulose 0.1
(3) Glycerin 3.0
(4) 1,3-butylene glycol 5.0
(5) Purified water remaining amount (6) perfume appropriate amount (7) preservative appropriate amount (8) glyceryl tri-2-ethylhexanoate 0.1
(9) Polyoxyethylene monooleate (20E.O.)
Sorbitan 1.0
(10) Ethyl alcohol 13.0
(11) Human squirrel purified water extract * 1 0.5
(12) Yeast extract * 2 0.5
(13) Peonies extract * 3 0.5
* 1: The extract produced in Example 3 was dissolved in 50 vol% water-containing 1,3-butylene glycol so as to have a content of 1%. * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. (manufacturing method)
A. Components (1) to (5) are dissolved by heating.
B. Components (6) to (10) are mixed and dissolved.
C. After cooling A, B and components (11) to (13) are added and mixed to obtain a pack.
The resulting pack has a moderate refreshing feeling and high tension, prevents excessive sebum secretion and prevents acne, gives the skin after packing a proper moisturizing feeling and stickiness, The pack was flexible.

[Example 16: Massage cream]
(Ingredient) (%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 2.5
(3) Lipophilic glyceryl monostearate 2.0
(4) Sorbitan sesquioleate 1.0
(5) Cetyl palmitate 1.0
(6) Dipentaerythritol fatty acid ester * 1 4.0
(7) Vaseline 20.0
(8) Liquid paraffin 28.0
(9) Dimethylpolysiloxane (100CS) 0.5
(10) Sodium hydroxide 0.1
(11) Dipropylene glycol 7.0
(12) Carboxyvinyl polymer 0.1
(13) Purified water Residual amount (14) Human volcano 80vol% hydrous ethyl alcohol extract * 2 1.0
(15) Birch extract * 3 1.0
(16) Neubara extract * 4 0.5
(17) Perfume appropriate amount * 1: Cosmol 168AR (Nisshin Oillio Group)
* 2: The extract produced in Example 1 was dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1%. * 3: manufactured by Maruzen Pharmaceutical Co., Ltd. * 4: manufactured by Maruzen Pharmaceutical Co., Ltd. (manufacturing method)
A. Ingredients (1) to (9) are dissolved by heating and maintained at 70 ° C.
B. Components (10) to (13) are dissolved by heating and maintained at 70 ° C.
C. A is added to B and emulsified.
D. After cooling C, components (14) to (17) were added and mixed to obtain a massage cream.
The resulting massage cream has a rich and smooth feeling of use, has a high massage effect, prevents excessive sebum secretion and prevents acne, moisturizes the skin and smoothes the skin It was a massage cream.

[Example 17: Liquid foundation]
(Ingredient) (%)
(1) Stearic acid 2.0
(2) Cetanol 0.5
(3) Behenyl alcohol 1.0
(4) Petrolatum 2.5
(5) Liquid paraffin 5.0
(6) Self-emulsifying glyceryl monostearate 1.0
(7) Preservative appropriate amount (8) Titanium oxide 6.0
(9) Color pigment 4.0
(10) Mica 2.0
(11) Talc 4.0
(12) Carboxymethylcellulose 0.2
(13) Bentonite 0.4
(14) Purified water Residual amount (15) Human liquor 50 vol% hydrous ethyl alcohol extract * 1 1.0
(16) Chamomile extract * 2 0.5
(17) Shobu extract * 3 0.5
(18) Fragrance Appropriate amount * 1: The extract produced in Example 2 dissolved in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% * 2: Maruzen Pharmaceutical Co., Ltd. * 3: Maruzen Pharmaceutical Co., Ltd. Made (Manufacturing method)
A. Components (1) to (7) are dissolved by heating.
B. Ingredients (8) to (11) are added to A, mixed uniformly, and kept at 70 ° C.
C. Ingredients (12) to (14) are dissolved by heating and maintained at 70 ° C.
D. B is added to C and emulsified.
E. After cooling D, components (15) to (18) were added and mixed to obtain a liquid foundation.
The obtained liquid foundation was a liquid foundation that had a light and expansive feeling of use, suppressed excessive sebum secretion, and prevented acne, resulting in a uniform and beautiful finish.

[Example 18: Aerosol type hair tonic]
(Ingredient) (%)
(1) Human volcano 80vol% hydrous ethyl alcohol extract * 1 1.5
(2) Isopropylmethylphenol 0.1
(3) Menthol 0.1
(4) Ethyl alcohol 40.0
(5) Perfume Appropriate amount (6) Purified water Remaining amount * 1 What was obtained by dissolving the extract produced in Example 1 in 50 vol% hydrous 1,3-butylene glycol so as to have a content of 1% (production method)
Components (1) to (6) are mixed. The aerosol container was filled with the propellant to obtain an aerosol type hair tonic.
The obtained hair tonic exhibited excellent hair restoration and hair growth effects when applied to the scalp.

[Example 19: Hair cream]
(Ingredient) (%)
(1) Beeswax 1.0
(2) Liquid paraffin 50.0
(3) Stearic acid 3.0
(4) Sorbitan sesquioleate 2.2
(5) Polyoxyethylene sorbitan monolaurate (20E.O.) 1.8
(6) dl-α-tocopherol acetate 0.2
(7) Methyl paraoxybenzoate 0.1
(8) Purified water Residual amount (9) Hitori-Sizuka 50vol% hydrous ethyl alcohol extract * 1 0.5
(10) Fragrance Appropriate amount * 1 What was obtained by dissolving the extract produced in Example 2 in 50 vol% 1,3-butylene glycol aqueous solution so as to have a content of 1%. Components (1) to (7) are dissolved by heating at 70 ° C.
B. Ingredient (8) is heated at 70 ° C.
C. Add A to B and emulsify.
D. Add (9) and (10) to C and cool to obtain a hair cream.
The obtained hair cream exhibited excellent hair restoration and hair growth effects when applied to the scalp.

  The testosterone 5α-reductase activity inhibitor and the androgen receptor antagonist of the present invention can be used as active ingredients for external preparations for skin, foodstuffs and the like. In particular, it is useful for skin external preparations such as hair nourishing agents and cosmetics.

Claims (7)

A testosterone 5α-reductase activity inhibitor comprising human lysizuka extract as an active ingredient. An androgen receptor antagonist comprising human lysizuka extract as an active ingredient. A hair nourishing agent containing a human lizard extract as an active ingredient. A skin external preparation for preventing and / or improving acne comprising a human lizard extract as an active ingredient. A skin external preparation for suppressing sebum secretion, which contains human lizard extract as an active ingredient. A method of suppressing the expression of androgenic activity by supplying a human lysizuka extract (except for a human therapeutic method). The method according to claim 6, wherein the expression of androgen activity is suppressed by at least a testosterone 5α-reductase activity inhibitory action and / or by an androgen receptor antagonistic action.