JP2002363085A - Antiandrogenic hormone preparation, hair growing cosmetic, inhibitor for sebum secretion and inhibitor for prostatic hypertrophy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antiandrogenic hormone preparation having an inhibitory effect on the expression of androgenic hormone action at different sites of action and good in safety and stability by bringing the preparation to have a testosterone 5 α-reductase inhibiting action and an androgen receptor-binding inhibiting action. SOLUTION: The antiandrogenic hormone preparation, the growing cosmetic, the inhibitor for sebum secretion and the inhibitor for prostatic hypertrophy contain a testosterone 5 α-reductase inhibitor and an androgen receptor-binding inhibitor extracted from plants belonging to Boraginaceae Ehretia (especially changbut) as effective ingredients.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to testosterone 5
An antiandrogen capable of inhibiting the expression of testosterone through an α-reductase inhibitory action and / or an androgen receptor binding inhibitory action, and a male that contains the antiandrogen and is an androgen-dependent disease Type baldness, hirsutism, seborrhea, acne, benign prostatic hyperplasia,
The present invention relates to a hair nourishing agent, a sebum secretion inhibitor, and a prostatic hypertrophy inhibitor that are effective in preventing and improving prostate tumors, precocious boyhood, and the like.

[0002]

2. Description of the Related Art Many steroid hormones are expressed in a molecular form secreted from a producing organ and bind to a receptor to exert their action. In the case of a male hormone collectively called androgen, for example, testosterone is a cell in a target organ. Once inside, it is reduced to 5α-dihydrotestosterone (5α-DHT) by testosterone 5α-reductase and then binds to a receptor to exert its action as an androgen.

[0003] The androgen is an important hormone, but when it acts excessively, various undesirable effects such as male pattern baldness, hirsutism, seborrhea, acne, benign prostatic hyperplasia, prostate tumors, precocious boyhood, etc. Induces symptoms. Therefore, means for improving these unfavorable symptoms by suppressing the action of excessive androgen are being studied. Specifically, a method for inhibiting the production of active 5α-DHT by inhibiting the action of testosterone 5α-reductase, which reduces testosterone to active 5α-DHT, and a method for suppressing the production of 5α-DHT produced from testosterone A method has been proposed in which binding to and inhibits the expression of androgen activity.

[0004] As a result, the effectiveness of cyproten acetate, oxendrone, chromadinone acetate and the like has been confirmed, but they have the disadvantage that they have undesirable side effects such as hormone-like action which is a steroid hormone derivative.

[0005] In addition, some crude drugs and extracts from plants show testosterone 5α-reductase inhibitory activity (see JP-A-60-146829).
Action of inhibiting the binding of DHT to its receptor (Japanese Unexamined Patent Publication No.
No. 4-3126).

[0006]

SUMMARY OF THE INVENTION However, there is a need for an antiandrogen which is excellent in safety and productivity, is inexpensive, and has a high testosterone 5α-reductase inhibitory action and / or an androgen receptor binding inhibitory action. The demands of the people are extremely strong, and at present the things that can be sufficiently satisfied have not been provided yet.

[0007] Under such circumstances, an object of the present invention is to solve the conventional problems and achieve the following objects. That is, the present invention provides a novel, potent, and safe antiandrogen containing a testosterone 5α-reductase inhibitor and / or an androgen receptor binding inhibitor as an active ingredient, and a hair restorer containing the antiandrogen. An object of the present invention is to provide a symptom, a sebum secretion inhibitor, and a prostatic hypertrophy inhibitor.

[0008]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventor has conducted intensive studies on a plant having an antiandrogenic effect from a large number of safe plants, and as a result, it has been found that the plants belonging to the genus Tishinoki belong to the genus Musaceae. (Ehreia) It was found that the plant extract had excellent testosterone 5α-reductase inhibitory activity and androgen receptor binding inhibitory activity.

[0009] That is, the genus Echinacea (Ehre
tia) The plant extract, especially the extract of leaves, stems, branches, or a mixture thereof, of Cangbat has a testosterone 5α-reductase inhibitory effect and an androgen receptor that suppress the onset of androgen action at different points of action. It has an inhibitory effect on body binding and is effective in preventing and improving male-type baldness, hirsutism, seborrhea, acne, benign prostatic hyperplasia, prostate tumors, precocious boyhood, etc., which are androgen-dependent diseases. The present inventors have found that a hair nourishing material, a sebum secretion inhibitor or a prostatic hypertrophy inhibitor effective for prevention and treatment can be obtained, and the present invention has been accomplished.

[0010] Accordingly, the present invention provides the following anti-androgen, and an agent for improving hair growth, a sebum secretion inhibitor, and a prostatic hypertrophy inhibitor.

[0011] The invention of claim 1 is an antiandrogen comprising as an active ingredient a testosterone 5α-reductase inhibitor extracted from a plant belonging to the genus Titanaceae in the genus Musaceae.

[0012] The invention of claim 2 is an antiandrogen comprising as an active ingredient an androgen receptor binding inhibitor, which is extracted from a plant belonging to the genus Titanaceae in the genus Musaceae.

[0013] The invention according to claim 3 is the anti-androgen according to claim 1 or 2, wherein the plant belonging to the genus Tisanoki in the family Virginaceae is one or more members selected from the group consisting of chungbat, maruchichisanoki, ryukyunishinoki and chishanoki. Agent.

According to a fourth aspect of the present invention, there is provided the antiandrogenic agent according to the third aspect, wherein a leaf, stem, branch, or a mixture thereof is used as a plant belonging to the genus Titanaceae.

According to a fifth aspect of the present invention, there is provided a hair nourishing cosmetic comprising the antiandrogen according to any one of the first to fourth aspects.

[0016] In the invention of claim 6, the hair restorer is further incorporated in an amount of 0.01 to 10% by mass based on the whole hair restoration cosmetic.
The hair-growth cosmetic composition according to the above description.

[0017] The invention of claim 7 is that the main agent for hair growth is vitamin E or a derivative thereof, cepharanthin, assembly, ginger, resorcin, pyridoxine or a derivative thereof, liquorice extract, carrot extract, garlic extract, enmeiso extract, glycyrrhizic acid. The hair restoration cosmetic according to claim 6, which is one or more selected from a derivative thereof and glycyrrhetinic acid or a derivative thereof.

[0018] The invention of claim 8 is a sebum secretion inhibitor comprising the antiandrogen agent according to any one of claims 1 to 4.

A ninth aspect of the present invention is a prostatic hypertrophy inhibitor containing the antiandrogen agent according to any one of the first to fourth aspects.

It should be noted that the extract of the genus Oryzaaceae, Tiger genus (especially Cangbat), which is a raw material for extraction of the antiandrogen of the present invention, is highly safe and has been used as a folk medicine, especially tea, but has a different effect. It has testosterone 5α-reductase inhibitory activity and androgen receptor binding inhibitory activity, and is a male hormone-dependent disease, male pattern baldness, hirsutism, seborrhea, acne, benign prostatic hyperplasia, prostate tumor, boy It is not known at all that it is effective for prevention and improvement of precocious ripening, etc., which is a new finding of the present inventors.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. The antiandrogen of the present invention contains testosterone 5α-reductase inhibitor and androgen receptor binding inhibitor extracted from a plant belonging to the genus Tistancaceae, as the active ingredients.

Here, the genus Echinacea (Ehr)
etia) As a plant, Cangbat (Ehret)
ia microphylla Lam. ), Marubuchishishanoki (Ehrenia dicksoni H
ance), Ryukyu Shanoki (Ehretia)
dichotama Bl. ) And Chishanoki (Eh)
retia ovalifolia Hassk. ) Is selected from the group consisting of one or more of these.

Cangbat (called "Fukumangi" in Japan) has a height of 1 and belongs to the genus Tishinoki of the sect.
~ 3m evergreen shrub, Ryukyu south of Amami Oshima, southern China,
Distributed in Malaysia and India. The leaves are dark green, clumping into short branches, are oval and 2-5 cm long.

This chungbat has been drunk as a folk medicine, especially as a tea, but it is not known at all that it has a testosterone 5α-reductase inhibitory action and an androgen receptor binding inhibitory action.

In the present invention, any part of the leaves, stems and branches of the chung bat may be used, or two or more different parts may be used in combination.

[0026] The genus Ehretti (Ehretti)
a) Although the details of the testosterone 5α-reductase inhibitor and the androgen receptor binding inhibitor contained in the plant are unknown, the testosterone 5α-reductase inhibitor and the androgen receptor binding inhibitor can be obtained by using the above-mentioned extraction raw materials by an extraction method generally used for extracting plants. .
The extract includes a liquid extract, a liquid diluent of the liquid extract, a dried product obtained by drying the liquid extract, or a crude product or a purified product thereof.

For example, it can be obtained by drying the genus Vulgaris, especially the leaves, stems, branches, or a mixture thereof of the jungbat, and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. be able to. Drying may be performed in the sun or using a commonly used dryer. Also, the leaves, stems,
The branch or a mixture thereof may be subjected to a pretreatment such as degreasing with a nonpolar solvent such as hexane or benzene, and then used as an extraction raw material. By performing a pretreatment such as degreasing, extraction of the leaves, stems, branches, or a mixture thereof of the chungbat with a polar solvent can be efficiently performed.

As the solvent used for the extraction, it is preferable to use water or a hydrophilic organic solvent or a mixture thereof at a temperature from room temperature to the boiling point of the solvent or lower.

The water that can be used as the extraction solvent includes pure water, tap water, well water, mineral water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments.
The treatment applied to water includes, for example, purification, heating, sterilization, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. Therefore, water that can be used as an extraction solvent in the present invention includes purified water, hot water, ion-exchanged water, physiological saline,
Phosphate buffer, phosphate buffered saline and the like are also included.

Examples of the hydrophilic organic solvent include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone;
1,3-butylene glycol, propylene glycol,
2 to 2 carbon atoms such as isopropylene glycol and glycerin
And a mixed solvent of these hydrophilic organic solvents and water. When a mixed solvent of water and a hydrophilic organic solvent is used, in the case of a lower alcohol, 1 to 10 parts by mass of water is used.
To 90 parts by mass, 1 to 40 parts by mass with respect to 10 parts by mass of water in the case of lower aliphatic ketone, water 1 in the case of polyhydric alcohol.
It is preferable to add 10 to 90 parts by mass with respect to 0 parts by mass.

In the present invention, a testosterone 5α-reductase inhibitor and an androgen receptor binding inhibitor do not need to employ a special extraction method, and can be extracted at room temperature or under reflux using any apparatus. be able to.

More specifically, a plant belonging to the genus Titanaceae (especially the leaves, stems, branches, or a mixture thereof) of the genus Trigonaceae is placed in a treatment tank filled with an extraction solvent.
After stirring for 30 minutes to 2 hours to elute the soluble component with occasional stirring as necessary, the solid was removed by filtration,
The extract is obtained by distilling off the extraction solvent from the obtained extract and drying. The amount of the extraction solvent is usually 5 to 15 times the mass of the extraction raw material (mass ratio), and the extraction conditions are usually 50 to 95 ° C. and 1 to 4 when water is used as the extraction solvent.
About an hour. Further, when a mixed solvent of water and ethanol is used as the extraction solvent, it is usually 3 to 40 ° C to 80 ° C.
It is about 0 minutes to 4 hours. The extract obtained by extraction with a solvent can be used as an active ingredient of the anti-androgen agent of the present invention by directly blending it if the extraction solvent has high safety, Dried products are easier to use.

The obtained extract is diluted, concentrated, dried, and dried in accordance with a conventional method to obtain a diluent or concentrate of the extract, a dried product of the extract, or a crude product or a purified product thereof. A treatment such as purification may be performed.

The obtained extract can be used as an antiandrogen as it is, but a concentrated solution or a dried product thereof is more easily used. In order to obtain a dried extract, a carrier such as dextrin or cyclodextrin may be added to improve the hygroscopicity.

Further, since the plants belonging to the genus Vulgaris, such as Cangbat, have a peculiar odor, it is possible to carry out purification for the purpose of decolorization, deodorization, etc. within a range that does not reduce the physiological activity. However, when it is added to hair cosmetics and the like, it is not used in large quantities, so that there is no practical problem even if it is not purified. The purification can be specifically performed by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like.

The antiandrogen of the present invention may be mixed with other natural extracts having an inhibitory effect on testosterone 5α-reductase and / or an inhibitory effect on androgen receptor binding as an active ingredient, if necessary. be able to.

Such natural extracts include, for example,
Lantana root extract, spinach extract and oak extract, Himalayan saxifrage plant extract (especially extract of Bergenia clasifolia or Bergenia perprusens), ginger plant extract (especially ginger, pontok ginger, turmeric, halconum) , Grass roots,
Curcumin, curcuminoids such as curcumin, demethoxycurcumin, bisdemethoxycurcumin, etc. contained in rhizomes and roots of mango ginger, mango gadgets, etc.), orange peel extract, sage leaf and flower extract, peppermint Leaf extract, eucalyptus leaf extract, mugwort leaf extract, lavender flower extract, rose flower extract, or rosemary leaf extract, and the like. These can be used in combination (for details, see JP-A-8-31
JP-A-9923, JP-A-9-255568, JP-A-11-199503, JP-A-11-33523
No. 2, JP-A-11-255661, etc.).
In addition, the compounding ratio of the active ingredient is as follows: the extract of the plant belonging to the genus Vulgaris, the natural extract = 1: 0.01 to 1: 5.
(Mass ratio).

The antiandrogen containing the extract of the plant belonging to the genus Vulgaris of the present invention as an active ingredient can be used alone or in combination with a suitable auxiliary according to a conventional method for preparing a plant extract of this type. It can be formulated in the form of a dermatological agent, an oral agent, an injection, a suppository and the like.

Specifically, the dosage form of the dermatological preparation can be any dosage form such as a hair tonic, shampoo, rinse, lotion, cream, emulsion, pack, ointment, bath preparation and the like. As the internal preparation, tablets, capsules, powders, liquids and the like can be used. In this case, the compounding amount of the extract of the genus Vulgaris in the preparation (especially Changbatt) extract can be appropriately adjusted in consideration of the purpose of use, gender, symptoms, etc., but cannot be specified unconditionally.
The amount of the extract is about 0.005 to 10% by mass.

The antiandrogen of the present invention can inhibit the action of testosterone-5α-reductase in male pattern baldness, hirsutism, seborrhea, acne, benign prostatic hypertrophy, etc. In addition to being able to be used alone for all purposes meaning to inhibit binding to the body, it can be widely used as a component of any skin external preparation, cosmetic, pharmaceutical, quasi-drug, etc. Although it can be used, it is particularly suitable as a hair nourishing agent, a sebum secretion inhibitor, and a prostatic hypertrophy inhibitor.

In this case, when the antiandrogen of the present invention is incorporated into a hair restorer, the hair restorer is used in an amount of 0.01 to 10% by mass, preferably 0.1 to 5% by mass, based on the total amount of the hair restorer. mass%
It is preferable to mix them from the viewpoint of enhancing the hair growth effect.

The main agent for hair growth includes vitamin E or a derivative thereof, cepharanthin, assembly, ginger,
Resorcin, pyridoxine or its derivative, licorice extract, carrot extract, garlic extract, enmeso extract, glycyrrhizic acid or its derivative, glycyrrhetinic acid or its derivative, and the like.One of these alone or in combination of two or more Can be used.

When the antiandrogen of the present invention is used as a component of an external preparation for skin such as a nourishing agent or a sebum secretion inhibitor, any physiologically active substance or auxiliary agent depending on the intended use may be used.
For example, if astringents, bactericidal, antibacterial, whitening agents, ultraviolet absorbers, humectants, cell activators, anti-inflammatory / antiallergic agents, antioxidant / active oxygen scavengers, etc. are used in combination, products with more generality can be obtained. Become. Moreover, thereby, the synergistic action with the other active ingredient used in combination may bring about an excellent effect more than normally expected.

Examples of the astringent include citric acid or its salts, tartaric acid or its salts, lactic acid or its salts,
Aluminum chloride, aluminum potassium potassium, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, zinc paraphenolsulfonate, zinc sulfate, japonicus extract, Eights extract, Hamamelis extract, Genoshoko extract, chacatechins,
Hydridium extract, hypericum extract, rhubarb extract, cornflower extract, kizuta extract, cucumber extract, marronnier extract, salvia extract, melissa extract and the like. One of these alone or 2
More than one species can be used in combination.

Examples of the bactericidal and antibacterial agents include benzoic acid, sodium benzoate, paraoxybenzoic acid ester, distearylmethylammonium chloride, benzethonium chloride, chlorhexidine hydrochloride, photosensitive element 101, photosensitive element 201, salicylic acid, and salicylic acid. Sodium, sorbic acid, halocarban, resorcinol, parachlorophenol, phenoxyethanol, bisabolol, hinokitiol, menthol, chitosan, chitosan hydrolyzate, zeyu extract, kudin extract, emisoe extract, loquat extract, yucca extract, aloe extract, keiju extract, etc. These can be used alone or in combination of two or more.

Examples of the whitening agent include ascorbic acid or its derivatives, sulfur, placenta hydrolyzate, ellagic acid or its derivatives, kojic acid or its derivatives, glucosamine or its derivatives, arbutin or its derivatives, hydroxycinnamic acid or Derivatives, glutathione, arnica extract, gongo extract, soybean arbor extract, psycho extract, buffalo extract, ginseng mycelium culture or extract thereof, linden extract, peach leaf extract, aegis extract, kujin extract, juju extract, touki extract,
Yokuinin extract, oyster leaf extract, rhubarb extract, radish extract, hamamelis extract, horse chestnut extract, hypericum extract, oil-soluble licorice extract (licorice hydrophobic flavone, glabridine, grabrene, lycochalcone A) and the like, and one of these alone is used. Or a combination of two or more.

As the ultraviolet absorber, for example, β-
Isopropylfuranone derivatives, urocanic acid, ethyl urocanate, oxybenzone, oxybenzonesulfonic acid, tetrahydroxybenzophenone, dihydroxydimethoxybenzophenone, dihydroxybenzophenone, sinoxate, methyl diisopropylcinnamate, octyl methoxycinnamate, glyceryl paraaminobenzoate, paradimethylaminobenzoic acid Amyl, octyl para-dimethylbenzoate, para-aminobenzoic acid, ethyl para-aminobenzoate, titanium oxide, β-carotene, γ-oryzanol, rice bran extract, aloe extract, birch extract, birch extract, chamomile extract, henna extract, butterflies extract, ginkgo Leaf extract, chamomile extract, hawthorn extract, oil-soluble liquorice extract, etc. One may be used alone or in combination of two or more of.

Examples of the humectant include serine, glycine, threonine, alanine, collagen, hydrolyzed collagen, hydronectin, fibronectin, keratin, elastin, royal jelly, chondroitin sulfate heparin, glycerophospholipid, glyceroglycolipid, sphingolipids. Glycosphingolipids, linoleic acid or esters thereof, eicosapentaenoic acid or esters thereof, pectin, fermented product of bifidobacteria, lactic acid fermented product, yeast extract, litchi mycelium culture or extract thereof, wheat germ oil, avocado Oil, rice germ oil, jojoba oil, soybean phospholipid, γ-oryzanol, below oil extract, yokuinin extract, jiou extract, daisy extract, diatom extract, kidachi aloe extract, burdock extract, mannen wax extract, arnica Kiss, wheat bran and the like, may be used these alone or in combination of two or more.

Examples of the cell activator include riboflavin or a derivative thereof, pyridoxine or a derivative thereof,
Nicotinic acid or a derivative thereof, pantothenic acid or a derivative thereof, α-tocopherol or a derivative thereof, arnica extract, carrot extract, rape ginseng extract, loofah extract (saponin), sicon extract, oak extract, buttonpix extract, peony extract, mukuroji extract, safflower Extract, Ashitaba extract, loquat leaf extract, Hikikoshi extract, Sakinoshita extract, Huanggui extract, Salvia extract, garlic extract, Mannen wax extract, etc., and these can be used alone or in combination of two or more. .

Examples of the anti-inflammatory / antiallergic agent include azulene, allantoin, aminocaproic acid, indomethacin, lysozyme chloride, epsilon aminocaproic acid, oxybenzone, glycyrrhizic acid or a derivative thereof, glycyrrhetinic acid or a derivative thereof, and photosensitizer 301.
No. 401, diphenhydramine hydrochloride, tranexamic acid or a derivative thereof, adenosine phosphate, estradiol, ethrone, ethinyl estradiol, cortisone, hydrocortisone, prednisone, progesterone, corticosterone, arnica extract, intinko extract, sanshishi extract, juyak Extract, liquorice extract, syrup extract, mugwort extract, warmoko extract, gentian extract, psycho extract, senkyu extract, Achillea millefolium extract, spinach extract, perilla extract, etc., and one of these alone or 2
More than one species can be used in combination.

Examples of the antioxidant / active oxygen scavenger include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, baicalin, baicalein, superoxide dismutase, catalase, rosemary extract, melissa extract, and gongon extract. Age extract, loquat leaf extract, hop extract,
Hamamelis extract, Peony extract, Sage extract,
Kina extract, chamomile extract, eucalyptus extract, perilla extract, ginkgo leaf extract, thyme extract, cardamom extract, caraway extract, nutmeg extract, mace extract, laurel extract, clove extract, turmeric extract, willow extract, etc.
The species can be used alone or in combination of two or more.

When the antiandrogen of the present invention is used as a prostatic hypertrophy inhibitor, it is used by adding it to general foods, health foods, health functional foods, quasi-drugs and pharmaceuticals. As general foods, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks and other drinks (including concentrated stock solutions and powders for adjustment of these drinks); ice cream, ice sorbet, frozen desserts such as shaved ice; buckwheat, Noodles such as udon, harusame, gyoza skin, sweet potato skin, Chinese noodles, instant noodles, etc .; sweets such as candy, chewing gum, candy, gum, chocolate, tablet snacks, snacks, biscuits, jellies, jams, creams, baked goods, etc. Processed fish and animal products such as kamaboko, ham and sausage; dairy products such as processed milk and fermented milk; processed fats and oils and processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing;
Seasonings such as sauces; soups, stews, salads, prepared dishes, pickles; various other forms of health and nutritional supplements; pharmaceuticals such as tablets, capsules, drinks, troches and the like; Can be added together with auxiliary raw materials and additives usually used in the production of

In addition to the above-mentioned uses, the antiandrogen of the present invention can be added to pet foods such as dog foods and cat foods and livestock animals for the purpose of preventing and treating hair loss. .

[0054]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to Production Examples and Examples, but the present invention is not limited to the following Examples.

[Production Example 1] Cangbat extract Cangbat (scientific name: Ehreia microp)
(Hylla) 1000 g of 50% by mass ethanol (mass ratio of water to ethanol 1: 1) as extraction solvent in 100 g of the dried product of each part (leaves, stems and branches)
Was added, and the mixture was heated and extracted with a reflux extractor at 80 ° C. for 2 hours and filtered while hot. The same extraction treatment was performed on the residue. The obtained two extracts were combined, concentrated under reduced pressure, and dried to obtain extracts at each site. Table 1 shows the yield of extract for each site.
As shown in FIG.

[0056]

[Table 1]

Example 1 The extract of each part of the Cangbat of Production Example 1 was tested for testosterone 5α-reductase inhibitory activity by the following test method.

<Testosterone 5α-reductase inhibitory activity test> Testosterone (manufactured by Tokyo Chemical Industry Co., Ltd.) 4.2
mg in 1 mL of propylene glycol, and the 20
825 μL of 5 mM Tris-HCl buffer (pH 7.2) containing 1 mg / mL NADPH was added to μL and mixed.

Further, 80 μL of each sample solution and S-9 (rat liver homogenate: manufactured by Oriental Yeast Co., Ltd.)
Add 5 μL, mix and incubate at 37 ° C for 30 minutes.
I did it. Thereafter, 1 mL of methylene chloride was added to stop the reaction, and the mixture was vigorously shaken. Thereafter, the mixture was centrifuged, the methylene chloride layer was separated, and the reaction products such as dihydroxytestosterone and androstanediol were quantified by gas chromatography.

Separately, as a control, the same treatment (80 μL) was used in place of the sample solution in the same manner as above, and the reaction product was quantified. By calculating the ratio of the amount of the reaction product (total peak area) at the time of sample addition to the amount of the reaction product (total peak area) in this control, the testosterone 5α-reductase activity inhibition rate (%) was determined. Similarly, the testosterone 5α-reductase activity inhibition rate (%) at each concentration was determined by variously changing the sample concentration. From the results, a sample concentration IC ₅₀ inhibiting the enzyme activity by 50% was determined by interpolation. . Table 2 shows the results.

[0061]

[Table 2]

Example 2 The extract of each part of the Cangbat of Production Example 1 was tested for androgen receptor binding inhibitory activity by the following test method.

<Test of androgen receptor binding inhibitory effect> Androgen-dependent mouse breast cancer cells SC-3 cells were
MEM medium containing FBS (hereinafter abbreviated as MEM-2)
1.0 × 10 ⁴ cells / well / 100 using
Seed into a 96-well microplate at a cell density of μL,
The cells were cultured at 37 ° C. under 5% CO ₂ -95% air. 2
After 4 hours, the medium was replaced with a Ham F12 + MEM medium (hereinafter abbreviated as HMB medium) containing 0.5% BSA to which the sample and ^10-9 molar DHT were added, followed by culturing for 48 hours.

Thereafter, the medium was replaced with a MEM-2 medium containing 0.97 mM MTT, and after culturing for 2 hours, the medium was replaced with isopropanol to extract blue formazan formed in the cells. With respect to the isopropanol containing the eluted blue formazan, the absorbance at 570 nm where the absorption maximum point of blue formazan was measured.

In order to correct the influence of the adherent cells, the absorbance at 650 nm was also measured at the same time, and the difference between the two absorbances was used as a value proportional to the amount of blue formazan produced. Corrected absorbance).

In parallel with the above, each sample solution alone was used for SC-
To see the effect on the three cells, the same culture and measurement were performed by adding only each sample solution without adding DHT to the HMB medium. Further, as a control, a sample solution and D
The same measurement was performed when the cells were cultured in the HMB medium to which HT was not added, and when the cells were cultured in HMB medium to which only DHT was added without adding the sample solution. From each measurement result, a binding inhibition rate (%) showing an anti-androgen action was calculated by the following equation.

[0067]

(Equation 1) However, A: Absorbance when DHT is added and no sample solution is added B: Absorbance when DHT is not added and no sample solution is added C: Absorbance when DHT is added and a sample solution is added D: No DHT is added and a sample solution is added Absorbance in case of

Next, the concentration of the sample solution was gradually reduced, and the androgen binding inhibition rate (%) at each concentration was similarly obtained, and the androgen binding inhibition rate at the time of adding 50 ppm was calculated. Table 3 shows the results.

[0069]

[Table 3]

Example 3 10 males aged 30 to 47 years with symptoms of male pattern baldness and seborrheic dermatitis of the head
The names were divided into a use group and a non-use group of 5 persons each. The use group was given a 50% ethanol aqueous solution containing 0.2% by mass of the 50% ethanol extract of Cangbat stalk of Production Example 1 for 3 weeks and 2 days a day. In the morning and evening, the hair tonic was used under the same conditions instead of the usual hair tonic.

On the test start date and the test end date (after 3 weeks), all the members were washed under the same conditions, and the number of hair loss at that time was measured. In addition, in order to adjust the conditions, the hair was washed under the same conditions 24 hours before the hair was washed for counting the number of depilation. Table 4 shows the results.

[0072]

[Table 4] From the results in Table 4, it was confirmed that the use of the Cangbat extract of the present invention clearly reduced the number of depilation.

Example 4 Hair Tonic Hair Tonic The following raw materials were treated by a conventional method of hair tonic production.
Hair nourishing hair tonics were manufactured. Purified water 70.0 parts by mass Changbat stem 50% ethanol extract (Production Example 1) 0.2 parts by mass Pyridoxine hydrochloride 0.1 parts by mass Resorcin 0.01 parts by mass D-pantothenyl alcohol 0.1 parts by mass Glycyrrhizic acid Dipotassium 0.1 parts by mass l-menthol 0.05 parts by mass 1,3-butylene glycol 4.0 parts by mass Carrot extract 0.5 parts by mass Ethanol 25.0 parts by mass Perfume

Example 5 Hair Nourishing Hair Tonic The following raw materials were treated by a conventional method of hair tonic production.
Hair nourishing hair tonics were manufactured. Purified water 70.0 parts by mass Chungbat stem 50% ethanol extract (Production Example 1) 0.2 parts by mass Pyridoxine hydrochloride 0.1 parts by mass Resorcin 0.01 parts by mass D-pantothenyl alcohol 0.1 parts by mass Assembly 0 0.1 parts by mass 1-menthol 0.05 parts by mass 1,3-butylene glycol 4.0 parts by mass Vitamin E 0.5 parts by mass Ethanol 25.0 parts by mass Perfume

[Example 6] Lotion A lotion having a sebum secretion inhibitory action was produced by treating the following ingredients by a conventional method for producing a lotion. Purified water 70.0 parts by mass Cangbat branch 50% ethanol extract (Production Example 1) 0.2 parts by mass Dipotassium glycyrrhizinate 0.2 parts by mass 1,3-butylene glycol 4.0 parts by mass Oleyl alcohol 4.0 parts by mass Parts Polyoxyethylene sorbitan monolaurate (20EO) 1.5 parts by mass Polyoxyethylene lauryl ether (20EO) 0.5 parts by mass Ethanol 15.0 parts by mass Preservatives appropriate amount Perfume appropriate amount

Example 7 Cream The following ingredients were treated by a conventional method for producing a cream to produce a cream having a sebum secretion inhibiting effect. Stearyl glycyl retinate 0.1 parts by mass Cangbat leaf 50% ethanol extract (Production Example 1) 0.2 parts by mass Beeswax 10.0 parts by mass Cetanol 5.0 parts by mass Hydrophilic lanolin 8.0 parts by mass Squalane 35 0.5 parts by mass Glyceryl monostearate 2.0 parts by mass γ-oryzanol 0.05 parts by mass Purified water 40.0 parts by mass Polyoxyethylene sorbitan monolaurate (20EO) 2.0 parts by mass Polyethylene glycol 0.5 Parts by mass Preservatives appropriate amount Fragrance appropriate amount

Example 8 Candy The following raw materials were treated by a conventional method for producing candy to produce candy having an inhibitory action on prostatic hypertrophy. 70 parts by weight of sucrose 30 parts by weight of starch syrup 30 parts by weight of citric acid 0.1 part by weight of fragrance 0.1 part by weight Chungbat stalk 50% ethanol extract (Production Example 1) 0.01 part by weight

Example 9 Chewing gum The following raw materials were treated by a conventional method of chewing gum production to produce a chewing gum having a prostatic hypertrophy inhibitory action. Chewing gum base 70 parts by mass Sucrose 54 parts by mass Syrup 20 parts by mass Softening agent 4 parts by mass Perfume (mint oil) 1 part by mass Cangbat branch 50% ethanol extract (Production Example 1) 1 part by mass

It should be noted that in Examples 4 to 7 according to the present invention, irritation to the skin or scalp,
No sensitization or side effects were observed, and both showed good storage stability.

[0080]

As described above, according to the present invention,
By having a testosterone 5α-reductase inhibitory action and an androgen receptor binding inhibitory action, an antiandrogen having an effect of suppressing the expression of androgen action at different points of action, and having good safety and stability. Obtainable.

Further, the nourishing agent, sebum secretion inhibitor and prostatic hyperplasia inhibitor containing the antiandrogen agent of the present invention can be used for androgen-dependent diseases such as androgenetic baldness, hirsutism and seborrhea. , Acne, benign prostatic hyperplasia, prostate tumors, precocious boys, etc.

[Procedure amendment]

[Submission date] June 1, 2001 (2001.6.1)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Name of invention

[Correction method] Change

[Correction contents]

[Title of the Invention] Anti-androgen, hair-growth cosmetic,
Sebum secretion inhibitor and prostatic hypertrophy inhibitor

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0001

[Correction method] Change

[Correction contents]

[0001]

TECHNICAL FIELD The present invention relates to testosterone 5
An antiandrogen capable of inhibiting the expression of testosterone through an α-reductase inhibitory action and / or an androgen receptor binding inhibitory action, and a male that contains the antiandrogen and is an androgen-dependent disease Type baldness, hirsutism, seborrhea, acne, benign prostatic hyperplasia,
The present invention relates to a hair nourishing cosmetic, a sebum secretion inhibitor, and a prostatic hypertrophy inhibitor that are effective in preventing and improving prostate tumors, precocious boyhood, and the like.

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0007

[Correction method] Change

[Correction contents]

[0007] Under such circumstances, an object of the present invention is to solve the conventional problems and achieve the following objects. That is, the present invention provides a novel, powerful, and safe anti-androgen containing a testosterone 5α-reductase inhibitor and / or an androgen receptor binding inhibitor as an active ingredient, and a hair restoration cosmetic containing the anti-androgen. It is an object of the present invention to provide a preparation, a sebum secretion inhibitor, and a prostatic hypertrophy inhibitor.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0009

[Correction method] Change

[Correction contents]

[0009] That is, the genus Echinacea (Ehre
tia) The plant extract, especially the extract of leaves, stems, branches, or a mixture thereof, of Cangbat has a testosterone 5α-reductase inhibitory effect and an androgen receptor that suppress the onset of androgen action at different points of action. It has an inhibitory effect on body binding and is effective in preventing and improving male-type baldness, hirsutism, seborrhea, acne, benign prostatic hyperplasia, prostate tumors, precocious boyhood, etc., which are androgen-dependent diseases. The present inventors have found that a hair nourishing cosmetic, a sebum secretion inhibitor or a prostatic hypertrophy inhibitor effective for prevention and treatment can be obtained, and the present invention has been accomplished.

[Procedure amendment 5]

[Document name to be amended] Statement

[Correction target item name] 0010

[Correction method] Change

[Correction contents]

[0010] Accordingly, the present invention provides the following antiandrogen, and a hair nourishing cosmetic, a sebum secretion inhibitor and a prostatic hypertrophy inhibitor.

[Procedure amendment 6]

[Document name to be amended] Statement

[Correction target item name] 0040

[Correction method] Change

[Correction contents]

The antiandrogen of the present invention can inhibit the action of testosterone-5α-reductase in male pattern baldness, hirsutism, seborrhea, acne, benign prostatic hypertrophy, etc., and can inhibit 5α-DHT from androgen receptor. In addition to being able to be used alone for all purposes meaning to inhibit binding to the body, it can be widely used as a component of any skin external preparation, cosmetic, pharmaceutical, quasi-drug, etc. Although it can be used, it is particularly suitable as a hair nourishing cosmetic, a sebum secretion inhibitor, and a prostatic hypertrophy inhibitor.

[Procedure amendment 7]

[Document name to be amended] Statement

[Correction target item name] 0041

[Correction method] Change

[Correction contents]

In this case, when the antiandrogen of the present invention is incorporated into a hair-growing cosmetic, the hair-growing agent is used in an amount of 0.01 to 10% by mass, especially 0.1 to 5% by mass, based on the total hair-growing cosmetic. %
It is preferable to mix them from the viewpoint of enhancing the hair growth effect.

[Procedure amendment 8]

[Document name to be amended] Statement

[Correction target item name] 0043

[Correction method] Change

[Correction contents]

When the antiandrogen of the present invention is used as a component of a skin external preparation such as a hair nourishing cosmetic or a sebum secretion inhibitor, any physiologically active substance or auxiliary depending on the intended use may be used.
For example, if astringents, disinfectants, antibacterial agents, whitening agents, ultraviolet absorbers, humectants, cell activators, anti-inflammatory / antiallergic agents, antioxidants / active oxygen scavengers, etc. are used in combination, products with more generality can be obtained. Become. Further, thereby, synergism with other active ingredients used in combination may bring about superior effects more than normally expected.

[Procedure amendment 9]

[Document name to be amended] Statement

[Correction target item name] 0081

[Correction method] Change

[Correction contents]

The hair nourishing cosmetic, sebum secretion inhibitor and prostatic hypertrophy inhibitor containing the antiandrogen of the present invention can be used for androgen-dependent diseases such as androgenetic baldness, hirsutism, seborrhea, etc. It is extremely effective in preventing and improving acne, benign prostatic hyperplasia, prostate tumors, precocious boyhood, etc.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 7/00 A61K 7/00 CDH K 7/06 7/06 31/05 31/05 31/19 31/19 31/355 31/355 31/4415 31/4415 31/4725 31/4725 31/704 31/704 A61P 5/28 A61P 5/28 13/08 13/08 17/08 17/08 17/14 17/14 43/00 111 43/00 111 (72) Inventor Naoko Kishida 14703-10 Mukotocho, Onomichi-shi, Hiroshima Maruzen Pharmaceutical Co., Ltd.F-term (reference) 4C083 AA111 AA112 AC102 AC122 AC471 AC642 AC851 AD531 AD532 AD631 AD632 AD661 AD662 BB53 CC37 DD23 EE22 4C086 AA01 AA02 BA09 BC18 BC30 EA10 GA07 MA01 MA04 MA63 NA14 ZA92 ZC24 ZC29 4C088 AB12 AB18 AB38 AB60 AB67 AB81 AB85 AC05 AC06 BA08 CA03 MA01 NA14 ZA81 ZA89 ZA92 ZC10 A01 MA01 MA01

Claims (9)

[Claims] 1. An antiandrogen comprising as an active ingredient a testosterone 5α-reductase inhibitor extracted from a plant belonging to the genus Titanaceae in the family Virginaceae. 2. An antiandrogen comprising, as an active ingredient, an androgen receptor binding inhibitor extracted from a plant belonging to the genus Tistancaceae. 3. The antiandrogenic agent according to claim 1 or 2, wherein the plant belonging to the genus Tisanoki in the family Musaceae is one or two or more members selected from the group consisting of chungbat, marubuchishishanki, ryukyuchinoshiki and chishanoki. 4. The antiandrogenic agent according to claim 3, wherein a leaf, stem, branch, or a mixed portion thereof is used as a plant of the genus Titanaceae in the family Musaceae. 5. A hair-restoring cosmetic comprising the anti-androgen according to any one of claims 1 to 4. 6. The hair restoration cosmetic according to claim 5, further comprising 0.01 to 10% by mass of a hair restoration main agent based on the whole hair restoration cosmetic. 7. The hair restorer comprises vitamin E or a derivative thereof, cepharanthin, assembly, ginger, resorcinol, pyridoxine or a derivative thereof, liquorice extract,
The hair restoration cosmetic according to claim 6, which is one or more kinds selected from a carrot extract, a garlic extract, an enamel extract, glycyrrhizic acid or a derivative thereof, and glycyrrhetinic acid or a derivative thereof. 8. A sebum secretion inhibitor comprising the antiandrogen agent according to any one of claims 1 to 4. 9. A prostatic hypertrophy inhibitor comprising the antiandrogen agent according to any one of claims 1 to 4.