JPH07278003A - Testosterone-5α-reductase inhibitor - Google Patents

Abstract

(57) [Summary] [PROBLEMS] To provide a testosterone-5α-reductase inhibitor which is excellent in reductase inhibitory effect, effective in preventing hair loss, hair nourishment and hair growth, and excellent in safety. [Composition] Sasanqua, Camellia, Camellia, Camellia, White magnolia, Antirrhinum majus, Stinkweed, Shishigashira, Rhododendron, Camphor tree, Red pine, Alaska, Ubamegashi, Akamegashiwa, Kinshibai plants, Khamin
Chan, Chum HetThet, Henna, Curculigo orchioide
A testosterone-5α-reductase inhibitor containing at least one s, each Ranoolifia crude drug and at least one extract of each seaweed of Kajime, Anahaosa, Oobamoku, Iwahigashi, Ishige, and Amiyouyo. [Effect] The above-mentioned inhibitor has a hair-growth / hair-growth effect.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to testosterone-5α.
-For more information on reductase inhibitors, see
[Camellia sasanqua], Camellia sasanqu
a], camellia [Camellia japonica], kobushi [Magnolia k
obus], White magnolia [Magnolia denudata], Snapdragon [Antirrhinum majus Linn.]
ronicapersica Poir.], Shishigashira [cv. Shishigashi
ra], Rhodophyta, camphor [Cinnamomum Camphor
a], Japanese red pine [Pinus densiflora], Arakashi [Quercu
s glauca], Ubamegashi [Quercus phillyraeoides],
Red wrinkle [Mallotus japonicus]
ericum patulum] plants or Khamin Chan [Curc
uma Longa], Chum Het Thet [Cassia alata Linn.], H
enna [Lawsoniainermis Linn.], Curculigo orchioides
[Curculigo orchioides], Ranoolifia [Rauvolfia Ser
[Pentina] herbal medicine or Kajime [Ecklonia cav
a], Ana Aosa [Ulra pertusa], Oba Moku [Sargas
sum ringgoldianum], sardine [Myelophycus caespito
sus], Ishige okamurai, Amiyou
and a testosterone-5α-reductase inhibitor containing an extract extracted with water and / or an organic solvent of each seaweed of D.

[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 mechanism of action of the hair-growth ingredients 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, there is a tendency to use the substance as a hair-growth / hair-growth agent, paying attention to 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 of 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 and JP-A-6.
1-7205), aromatic alcohols, aromatic carboxylic acids (JP-A-57-53401), other natural extracts and compounds (JP-A-60-146829, JP-A-5-146829).
9-59606, JP-A-59-59607, etc.), and bicyclic condensed 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-restoring / hair-growth effect is widespread and variously used is that the enzyme activity of testosterone-5α-reductase and physiological activity relating 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 similar or homologous chemically similar compound, its isomers (structural isomers, tautomers, optical isomers, geometrical isomers, etc.) have a large presence or absence of the above-mentioned enzyme activity and physiological activity and its potency. 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 having a hair-growth / hair-growth effect have been proposed, and these conventional hair-growth / hair-growth agents (especially for hormones etc.) 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. , The result of the test, the plant, herbal medicine,
It was found that a substance extracted with seaweed water or / and an organic solvent can solve this problem, and completed the present invention.

[0011]

SUMMARY OF THE INVENTION In view of such a situation, the present inventors have made earnest studies, and as a result, have found that the southern camellia [Ca
mellia sasanqua] (hereinafter simply referred to as “Sasanqua”), camellia [Camellia sasanqua] (hereinafter simply referred to as “camellia”), camellia [Camellia japonica] (hereinafter simply referred to as “camellia”), magnolia family Magnolia k
obus] (hereinafter simply referred to as "kobushi")
[Magnolia denudata] (hereinafter simply referred to as "saku magne"), Antirrhinum ma
jus Linn.] (hereinafter simply referred to as “Snapdragon”), Veronica persica Poir.] (hereinafter simply referred to as “Great Stuff”), Shishigashira of the maple family [cv.
Shishigashira] (hereinafter simply referred to as “shishigashira”), dragonfly, camphoraceae of the camphoraceae [Cinnamomum Camph
ora] (hereinafter simply referred to as “camphor tree”), Pinus densiflora (Pinus densiflora) (hereinafter simply referred to as “Pinus densiflora”), Quercus glauca (hereinafter simply referred to as “Arakasi”) of the beech family, Quercus phillyra
eoides] (hereinafter simply referred to as “Ubamegashi”), Mallotus japonicus] (hereinafter simply referred to as “Akamegashiwa”), Hypericum patulum (Hypericum patulum) (hereinafter simply referred to as “Kinshibai”) plant, or Khamin Chan [Curcuma Long
a] (hereinafter simply referred to as “Khamin Chan”), Chum Het Th
et [Cassia alata Linn.] (hereinafter simply “Chum Het Thet”
Henna [Lawsonia inermis Linn.] (Hereinafter simply referred to as "Henna"), Curculigo Orchioides [Curculig
o orchioides] (hereinafter simply referred to as “Curculigo Orchioides”), Ranoolifia [Rauvolfia Serpentina] (hereinafter simply referred to as “Ranoolifia”), or Ecklonia cava] (hereinafter simply referred to as “squid”) belonging to the family Kajime [Ulra
pertusa] (hereinafter simply referred to as “Ana-Aosa”), a genus of the genus Honda Walla [Sargassumringgoldian]
um] (hereinafter simply referred to as “Obermoku”), a sardine bear of the genus Habarodoki (Myelophycus caespitosus)
Water of each seaweed (hereinafter simply referred to as “Iwahige”), Ishige okamurai (hereinafter simply referred to as “Ishige”), and Ami-moyo (Miccrodictyon japonicum) (hereinafter simply referred to as “Amimoyo”) or / It was also possible to obtain the finding that an extract extracted with an organic solvent exhibits an excellent effect on inhibiting testosterone-5α-reductase.

The extract of the present invention may be extracted from any of the above-mentioned plants and herbs such as flowers, skins, fruits, leaves, stems, roots, seeds and seaweeds. More effective raw material selection is desirable.

The extract can be used in a dried state after removing the solvent, or can be used in a state of being dissolved in the solvent.

A hair growth and nourishing agent can be prepared by incorporating at least one kind of this extract.

Since the above-mentioned various plants, crude drugs and seaweeds are not toxic to the human body, the amount to be added to the hair-growth / hair-restoring agent is not particularly limited and can be selected within a wide range. ) In the total amount of 0.001 to 10% by weight
It is suitable to use within the range of 0.01 to 0.01
It is within the range of 2% by weight. This is because when the amount is 0.01% 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 effective.

The raw materials used in the present invention may be the above-mentioned plants, crude drugs, raw seaweed, or dried products.
It is preferable to use various plants, crude drugs, and seaweeds that have been dried in the shade for about 2 to 5 days to prevent spoilage.
Then, various active ingredients are extracted from the various plants, crude drugs and seaweed with water or / and an organic solvent.

The solvent used to extract the active ingredient from the various plants, crude drugs and seaweed is water, lower 1
Polyhydric alcohols (eg methanol, ethanol, n-
Butanol, etc.), lower polyhydric alcohol (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),
It is carried out using a solvent selected from the group consisting of halogenated alkanes (for example, dichloromethane, chloroform and the like) and other aromatic hydrocarbons such as benzene and toluene.

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

The hair growth and nourishing agent of the present invention contains at least one active substance extracted from the plants, herbal medicines, and seaweeds with water or / and an organic solvent in a known manner in various known cosmetic bases. And then, Hear Tonic,
Hair cream, hair liquid, hair lotion,
It can be applied to pomades, hair shampoos, hair rinses, emulsions and other cosmetics. Further, the shape of the cosmetic is
It can be applied in various forms such as solution, sol-gel, emulsion, ointment, oil, wax and spray (aerosol).

Further, the hair restorer and hair restorer of the present invention can of course be used in combination with other known hair restorers and hair restorers,
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 has a wide variety, it has not only a 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.

[0023]

【Example】

 (Example 1)

Preparation of various extracts from plants and seaweed: 1 part of pulverized powder or ground powder of any of the above-mentioned plants and seaweed,
Add 10 parts of water or / and an organic solvent, and heat and extract under reflux for about 1 hour on a boiling water bath. The obtained extract is filtered,
Extracts of various solvents from each plant and seaweed are obtained.

Preparation of various extracts from crude drug: 100 parts of water or / and organic solvent is added to 1 part of the above-mentioned various crude drug pieces or ground powder, and the mixture is heated under reflux for about 1 hour for extraction on a boiling water bath. The obtained extract is concentrated to dryness under reduced pressure to obtain extracts from various crude drugs with various solvents.

Example 2 Formulation example (all contents are wt%):

(1) Hair Tonic [Component] Ethanol 60.0 Polyoxyethylene hydrogenated castor oil (EO 60 mol) 0.5 Glycerin 3.0 Menthol 0.2 Sasanqua extract (dry matter) 0.3 Perfume And Dye Appropriate amount Ion-exchanged water Total amount is 100

(2) Hair Tonic [Component] Ethanol 60.0 Polyoxyethylene hydrogenated castor oil (EO 60 mol) 0.5 Glycerin 3.0 Menthol 0.2 Khamin Chan extract (dry product) 0.3 Fragrances and dyes Appropriate amount Ion-exchanged water Total amount is 100

(3) Hair Tonic [Component] Ethanol 60.0 Polyoxyethylene hydrogenated castor oil (EO 60 mol) 0.5 Glycerin 3.0 Menthol 0.2 Kajime extract (dry matter) 0.3 Perfume And Dye Appropriate amount Ion-exchanged water Total amount is 100

(4) Shampoo [Components] Sodium polyoxyethylene alkyl ether sulfate (EO 2 mol) 15.0 Coconut oil aliphatic diethanolamide 5.0 Glycerin 3.0 Southern salmon extract (dry matter) 0.2 Red pine extract (dry matter) 0.2 Ethanol 5.0 Fragrance and preservatives Appropriate amount Ion-exchanged water Total 100

(5) Hair Cream [Component] Liquid paraffin 20.0 Solid paraffin 3.0 Polyoxyethylene cetyl ether (EO 15 mol) 2.0 Sorbitan sesquioleate 1.0 Khamin Chan extract (dry product) 0.2 Ethanol 10.0 Potassium hydroxide 0.1 Glycerin 3.0 Fragrance and preservative Appropriate amount Ion-exchanged water Total 100

(6) Ointment [Ingredient] Salix beeswax 5.0 Purified lanolin 5.0 Ami-moyo extract (dry product) 1.0 Perfume 0.1 Vaseline The total amount is 100

(Example 3) Testosterone-5α-reductase inhibitory effect test method:

3.0 μmol of testosterone was dissolved in 10 drops of propylene glycol, 5 ml of Tris-HCl buffer solution (pH 7.2) was added, and NADPH was added to 5 m in order.
g, 1 ml of the enzyme solution (5α-reductase) and a sample (the substance obtained in Example 1) were added and incubated at 37 ° C. for 1 hour, 50 ml of dichloromethane was added to stop the reaction, and the dichloromethane layer was separated. After drying 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: The reaction rate of the subject to which no inhibitor consisting of each extract was added was regarded as 100% (inhibition rate 0%),
The inhibition 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, it was clearly recognized that various plants, herbal medicines and extracts of seaweed had an inhibitory effect on 5α-reductase inhibition.

(Example 4) Hair growth effect test method: Examples (2) -1, (2) -2,
(2) A method of uniformly applying 2 ml of the hair tonic prepared in (3) -3 to the head twice a day, with 10 subjects each for male pattern baldness patients (ages 25 to 55 years old) as subjects. Using. The evaluation was carried out 3 months and 6 months after the start of the test, and the hair growth state of 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 each of the plant, crude drug and seaweed extracts.

[0042]

The various plants, crude drugs and seaweed extracts of the present invention extracted with water or / and an organic solvent are:
It has an excellent testosterone-5α-reductase inhibitory effect.

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

Claims (6)

[Claims] 1. A sasanqua [Camellia sasanqua], a camellia [Camellia sasanqua], a camellia [Camellia japonic]
a], Magnolia kobus, Magnolia magnolia
ia denudata], snapdragon [Antirrhinum majus Lin
n.], Veronica persica Poir.], Shishigashira [cv. Shishigashira], Sugar beetle, Camphora, Cinnamomum Camphora, Pinus densif
lora], Arakashi [Quercus glauca], Ubamegashi [Que
rcus phillyraeoides], Red wrinkle [Mallotus japo
nicus], Quercus chinensis [Hypericum patulum], testosterone-5α containing at least one extract extracted with water or / and an organic solvent of each plant
-Reductase inhibitors. 2. A hair restorer / hair nourishing agent, which comprises the extract according to claim (1). 3. Khamin Chan [Curcuma Longa], Chum H
et Thet [Cassiaalata Linn.], Henna [Lawsonia inerm
is Linn.], Curculigo orchioides [Curculigo orchioi
des], Ranoolifia [Rauvolfia Serpentina], testosterone-5 containing at least one extract of each crude drug extracted with water or / and an organic solvent
α-reductase inhibitor. 4. A hair restorer / hair nourishing agent comprising the extract according to claim (3). 5. Kajime [Ecklonia cava], Ana Aosa
[Ulra pertusa], Obama Moku [Sargassum ringgoldian
um], sardine [Myelophycus caespitosus], Ishige [I
shige okamurai], Ami Moyou [Miccrodictyon japonic
[um], water of each seaweed and / or a testosterone-5α-reductase inhibitor containing at least one extract extracted with an organic solvent. 6. A hair restorer / hair nourishing agent comprising the extract according to claim (5).