JPH07278006A - Testosterone-5alpha-reductase inhibitor - Google Patents

Abstract

PURPOSE:To obtain a testosterone-5alpha-reductase inhibitor which is excellent in the inhibitory action against the reductase and effective for hair-falling prevention, hair growth stimulation and hair tonic action with high safety. CONSTITUTION:The lnhibitor against testosterone-5alpha-reductase contains at least one of extracts from fruits selected from the group consisting of the following fungi: Trametes sanguinea, Trametes cinnabarina, Polyporus confluens, Tyromyces lacteus, Phellinus igniarius, Pheurotus citrinopileatus, Pholiota nameko, Flammulina velutipes, Gomphidius roseus.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to testosterone-5α.
-For more details on the reductase inhibitors, refer to Trametes sanguinea and Trametes cinna.
barina], Ningyotake (Polyporus confluens),
Tyromyces lacteus, Physcomitrella patens
ellinus igniarius], Pleurotus citrin
opileatus], Nameko [Pholiota nameko], Enokitake [Flammulina velutipes], Ougitake [Gomphidius]
roseus] fruit juice of testosterone-5α-containing extract extracted with water and / or organic solvent
The present invention relates to a reductase inhibitor and a hair growth / hair nourishing agent having excellent hair growth effects.

[0002]

2. Description of the Related Art There are many unknown aspects of the medical knowledge regarding hair loss and hair growth, and the physiological action mechanism of the hair-growth components used for these is often unknown. Presently, the causes of hair loss are endocrine abnormalities, hair cycle abnormalities, autonomic nerve disorders, poor blood circulation, nutritional disorders, and others (hereditary, aging, etc.). Examples of conventional hair-growth ingredients include hormones such as estrogen (JP-A-60-38313), vitamins such as vitamin E, B ₂ , B ₆ , biotin, pantothenic acid, and other amino acids (peptide substance: special (Kaisho 61-7209), crude drug extracts such as assembly extracts, antiphlogistics such as diphenhydramine hydrochloride, humectants such as glycerin, scalp stimulants such as Photosensitizer 301, fungicides such as hinokitiol, and cooling agents such as ethanol. There is.

The hair-growth and hair-restoration agents are used by expecting a local effect by combining the above-mentioned hair-growth ingredients alone or in combination, and are used for hair-restoration, promotion of hair growth, dandruff, itch, inflammation prevention, thinning and hair loss. By taking preventive measures, the aim is to provide a comprehensive hair-growth and hair-growth effect.

Recently, the substance tends to be used as a hair nourishing and hair-growing agent, focusing on the properties of the substance, such as testosterone-5α-reductase inhibitory action, hair mother cell activating action and blood circulation promoting action.

The reason why the testosterone-5α-reductase inhibitor is used as a hair-growth / hair-growth agent is that a male hormone (testosterone) in the metabolic system is acted on by testosterone-5α-reductase to produce 5α-dihydrotestosterone. -It is believed that the hair roots are accumulated, and as a result, the hair roots are atrophied to attract hairs and baldness.

For example, as an example of a substance having a testosterone-5α-reductase inhibitory property, a carboxylic acid such as a higher fatty acid (JP-A-59-152308, JP-A-59-152308).
-172410, JP-A-59-172411, JP-A-61-5007, JP-A-61-5014, JP-A-61-7205, etc.), aromatic alcohols, aromatic carboxylic acids (JP-A-SHO) 57-53401), other natural extracts and compounds (JP-A-60-146829, JP-A-59-59606, JP-A-59-59607, etc.),
Examples include bicyclic fused ring compounds of bicyclic terpenes.

As the bicyclic condensed ring compound of the bicyclic terpenes, 5,6-dimethyl-8-isopropenyl-bicyclo [4,4,0] decen-1-one-3 (JP-A-59)
-53417), 4,8-dimethyl-2-isopropylidene-1,2,3a, 4,5,6-hexahydro-azulenone (6) or 3,6,8-tetramethyl-1,
2,4,7,8,8a-Hexahydro-azulenone (JP-A-59-53418, JP-A-59-55813)
No.), 4-methyl-1-isopropyl-bicyclo [3,3
1,0] hexen-3-one 2 and 4,6,6-trimethyl-bicyclo [3,1,1] hepten-3-one-
2 (JP-A-59-53419, JP-A-59-5581)
No. 2) etc.

Thus, the testosterone-5α-
The reason why the substance having reductase inhibitory properties or / and hair-restoration / hair-growth effect is widespread and variously used is that the oxygen activity of testosterone-5α-reductase and physiological activities related to hair-growth / hair-growth are This is because it is considered to be caused by having a specific correlation with the molecular structure of the chemical substance. Even if it is a chemically similar compound of the same kind or the same family, depending on its isomer (structural isomer, tautomer, optical isomer, geometric isomer, etc.), the presence or absence and the potency of the oxygen activity and physiological activity are large. different. The physiological activity effects of hair growth and hair growth of various substances are significantly different, and it is the current situation that the hair growth and hair growth effects of each material cannot be determined unless directly measured and searched.

[0009]

As described above, various substances have been proposed as substances having a hair-growth / hair-growth effect, and these conventional hair-growth / hair-growth agents (especially for hormones) have been proposed. Side effects occur, and the hair-growth and hair-growth effects are not always sufficient, and the development of more effective hair-growth and hair-growth agents is desired.

[0010] Therefore, the present inventors searched for various substances which are generally considered to be safe based on the above background, and which are excellent in reductase inhibitory effect, effective in preventing hair loss, hair nourishment and hair growth effect and safe. As a result of the test, it was found that a substance extracted from the various mushrooms (fruit bodies) with water or / and an organic solvent can solve this problem, and completed the present invention.

[0011]

[Means for Solving the Problems] In view of such a current situation, as a result of diligent studies, the present inventors have conducted studies on the genus Arcaceus, Trametes sanguinea (hereinafter simply referred to as “Ghilothus”) and Trametes. cinna
barina] (hereinafter simply referred to as “bamboo shoots”), Polyporus confluens] of the genus Tamachorei (hereinafter simply referred to as “boiled mushrooms”), Tyromyces lacteus] (hereinafter simply referred to as “boiled mushrooms”) of the genus Oscillatus, Mushroom mushrooms The genus Phellinus igniarius (hereinafter simply referred to as "Pleurotus edulis"), the oyster mushroom Pleurotus igniarius [Ph]
eurotus citrinopileatus] (hereinafter simply referred to as “oyster mushroom”), Phelliota nameko (Pholiota n
ameko] (hereinafter simply referred to as “nameko”) of the genus Enokitake (Flammulina velutipes) (hereinafter simply referred to as “enokitake”), and Gomphidius roseus] (hereinafter simply referred to as “Outaketake”) of the genus Aedes The extract group extracted from each fruit body with water or / and an organic solvent is testosterone-5.
It was possible to obtain the finding that it exhibits an excellent effect on α-reductase inhibition.

The extract of the present invention can be used in a dried state after removing the solvent, or can be used in a state of being dissolved in the solvent. Then, a hair nourishing / hair growth agent can be prepared by incorporating at least one kind of this extract.

Since the above-mentioned various mushrooms (fruit bodies) are not toxic to the human body, the amount to be added to the hair restorer / hair nourishing agent is not particularly limited and can be selected within a wide range. ), It is suitable to use within the range of 0.01 to 10% by weight, and preferably within the range of 0.1 to 2% by weight, based on the total amount. When the amount is 0.1% by weight or less, the hair-growth effect is weak, and even when the amount is 2% or more, a significant difference in effect is hardly recognized and it is not efficient.

The raw materials used in the present invention can be raw or dried products of the above-mentioned various mushrooms (fruit bodies).
It is preferable to use various fruiting bodies dried in the shade for about 2 to 5 days to prevent them from rotting. Then, various active ingredients are extracted from the various mushrooms (fruit bodies) with water and / or an organic solvent.

Solvents used to extract the active ingredient from the various fruiting bodies include water, lower monohydric alcohols (eg, methanol, ethanol, n-butanol), lower polyhydric alcohols (eg, ethylene). Glycol, propylene glycol, 1,3-butylene glycol, glycerin etc.), ethers (eg diethyl ether etc.), ketones (eg acetone, ethyl methyl ketone etc.), esters (eg ethyl acetate), halogenated alkanes ( (Eg, dichloromethane, chloroform, etc.), and other solvents selected from the group consisting of aromatic hydrocarbons such as benzene and toluene.

These solvents can be used alone, but a mixture of two or more kinds (for example, 20 to 80% aqueous ethanol, benzene: ethyl acetate (4: 1 mixture), 1,3)
-Butylene glycol aqueous solution).

The hair growth and hair nourishing agent of the present invention is prepared by mixing at least one active substance extracted from the fruiting body with water or / and an organic solvent into various known cosmetic bases by a conventional method. It can be applied to hair tonic, hair cream, hair liquid, hair lotion, pomade, hair shampoo, hair rinse, emulsion and other cosmetics. Further, the shape of the cosmetic can be applied in various shapes such as solution, sol-gel, emulsion, ointment, oil, wax, spray (aerosol) and the like.

Further, it is a matter of course that the hair restorer and hair restorer of the present invention can be used together with other known hair restorer and hair restorer,
An excellent synergistic effect can also be expected. Also, the hair restoration of the present invention,
After confirming that the hair nourishing agent is stable against various kinds of additives such as various surfactants, solvents, pigments, fragrances, preservatives, antioxidants, humectants, etc., it is applied together with these various additives. It is also possible.

Since the extract of the present invention is diverse, it has not only the 5α-reductase inhibitory activity but also a secondary effect of moisturizing action.

The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto.

[0021]

【Example】

Preparation of various extracts from fruiting bodies: 50 parts of extraction solvent is added to 1 part of each of the above fruiting bodies, and the mixture is heated under reflux for about 1 hour for extraction on a boiling water bath. After cooling, centrifuge (3000 rp
m, 10 minutes) etc. to perform the first solid-liquid separation. The supernatant liquid is taken, and the supernatant liquid is further filtered using a filter paper to
Use as the extract. On the other hand, the residue after the first solid-liquid separation is similarly extracted with 25 parts of extraction solvent on the boiling water bath for about 1 hour under reflux heating extraction and solid-liquid separation, filtration, etc., twice as in the previous time, and the first or All the extracts (filtrate) of the third time are combined and water or / and the organic solvent are distilled off under reduced pressure to obtain extracts from various fruiting bodies with various solvents.

Example 1 Formulation example (all contents are wt%):

(1) Hair Tonic [Ingredient] Ethanol 60 Polyoxyethylene hydrogenated castor oil (EO 60 moles) 0.5 Glycerin 3 Menthol 0.2 Ningyotake extract (dry matter) 0.2 Perfume and pigment Appropriate amount of ions Total amount of exchanged water is 100

(2) Shampoo [Component] Sodium polyoxyethylene alkyl ether sulfate (EO 2 mol) 15 Coconut oil fatty acid diethanolamide 5 Glycerin 3 Ginseng extract (dried product) 0.2 Ethanol 5 Perfume and preservative proper amount Ion-exchanged water is 100

(3) Hair Cream [Components] Liquid paraffin 20 Solid paraffin 3 Polyoxyethylene cetyl ether (EO 15 mol) 2 Sorbitan sesquioleate 1 Enokitake extract (dry matter) 0.5 Carboxyvinyl polymer 0.1 Ethanol 10 Potassium hydroxide 0.1 Glycerin 3 Fragrance and antiseptic Suitable amount Ion-exchanged water 100

(4) Hair lotion [ingredient] ethanol 20 glycerin 3 polyoxyethylene sorbitan monolaurate (EO 20 mol) 1 oscillaceae extract (dry matter) 0.5 perfume and preservative proper amount ion-exchanged water 100 in total To

(5) Ointment [Ingredient] White beeswax 5.0 Purified lanolin 5.0 Oyster mushroom extract (dry product) 1 Vaseline 89.0

(Example 2) Testosterone-5α-reductase inhibitory effect test method:
3.0 μmol of testosterone was dissolved in 10 drops of propylene glycol, and Tris-HCl buffer solution (pH 7.
2) Add 5 ml, NADPH 5 mg, enzyme solution (5α-reductase) 1 ml, sample (substance obtained in Example 1), and incubate at 37 ° C. for 1 hour, then add 50 ml of dichloromethane to react. After stopping, the dichloromethane layer was separated and dried under reduced pressure, the reaction product was confirmed by gas chromatography (column OV-17, column length 2 m, column temperature 250 ° C., FID).

The enzyme solution was S-9 (manufactured by Oriental Yeast Co., Ltd.) which was a supernatant fraction of SD rat liver homogenate.
Was used.

Inhibition rate: 100% (inhibition rate 0%) of the reaction rate in the case of not adding an inhibitor consisting of mushroom fruit body extract
The inhibitory rate is calculated by calculating the reaction amount with the inhibitor added. The calculation is as shown below.

[Equation 1]

A is the peak area of the testosterone of interest.
b is the peak area of the target dehydrotestosterone and androstanediol. a'is the peak area of testosterone due to the addition of the sample. b ′ is the peak area of dehydrotestosterone and androstanediol due to the addition of the sample.

[Table 1]

In Table 1 above, the reductase inhibitory effect was clearly recognized in the fruit body extract extracts against 5α-reductase inhibition.

(Example 3) Hair growth effect test method: 10 male pattern baldness patients (age 25-
A 55-year-old subject was used by applying the hair nick prepared in Example (1) -1 twice a day to the head evenly at a time of 2 ml. Evaluation is 3 after starting the test
It was carried out at the 6th and 6th months, and the hair growth state at the application site was observed.

Very effective ──── ++ Effective ──── ＋ A little effective ──── ± Ineffective ──── −

[Table 2]

In Table 2 above, a clear hair-growth effect was observed in the fruiting body extract.

[0036]

The extract of various mushrooms (fruit bodies) of the present invention extracted with water or / and an organic solvent has an excellent testosterone-5α-reductase inhibitory effect.

The above-mentioned testosterone-5α-reductase inhibitor is a substance extracted from a natural product which is generally considered to be safe and has no problem in terms of safety for the living body. In this case, the hair-growth / hair-growth agent has a very excellent hair-growth effect.

Claims (2)

[Claims] 1. A oyster mushroom (Trametes sanguinea), a mushroom (Trametes cinnabarina), and a garlic mushroom (Pol)
yporus confluens], Oyster mushroom [Tyromyces lacte
us], Phellinus igniarius], Pleurotus citrinopileatus], Nameko (Pholio)
ta nameko], enokitake [Flammulina velutipes],
A testosterone-5α-reductase inhibitor containing at least one fruiting body extract selected from the group consisting of fruiting bodies of Gomphidius roseus. 2. A hair restorer / hair nourishing agent comprising an extract obtained by extracting the mushroom (fruit body) according to claim 1 with water or / and an organic solvent.