JPH06128169A - Anti-male hormone agent - Google Patents

Abstract

PURPOSE:To obtain an anti-male hormone agent effective for preventing and treating various diseases related to male hormone, widely useful as medicines and cosmetics for preventing pimple and for hair, having no hormone-like action and high anti-male hormone activity. CONSTITUTION:An anti-male hormone agent comprises an extracted essence of wood part of a plant belonging to the genus Diospyros of the family Ebenaceae such as, Diospyros ebenum, Diospyros discolor, Diospyros KaKi, Diospyros assimilis, Diospyros maritima and Diospyros rorrisiana as an active ingredient.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antiandrogen agent using a plant extract.

[0002]

2. Description of the Related Art In the skin, sebum is necessary for preventing evaporation of water and for keeping the skin smooth, and also has a role of preventing foreign substances from entering the body. Also, sebum is necessary for the scalp to maintain the beauty of hair.

However, if its secretion is excessive, it becomes sticky and easily soiled, and pathogenic bacteria are easily propagated. Seborrhea, acne, dandruff and itching on the scalp, and male pattern baldness are all due to increased sebum secretion.

[0004] It is believed that the increase in sebum secretion is caused by the overactivity of male hormones. In addition to this, conventionally
It is known that hirsutism, androgenetic alopecia, acne, seborrhea, benign prostatic hyperplasia, prostate tumor, etc. are diseases associated with male hormones, and all are thought to be due to overactive male hormones. There is. In particular, various studies have revealed that 5α-dihydrotestosterone (DHT), which is a metabolite of testosterone, causes disease. Various antiandrogens have been used for the treatment of these diseases, and their action inhibits, for example, the activity of 5α-reductase that reduces testosterone to highly bioactive DHT in the target organ, or This is due to inhibition of the binding between the produced DHT and the receptor in the target cell.

However, these antiandrogens, such as cyproterone acetate, oxendron,
Chlormadinone acetate etc. is a steroid hormone derivative, so the effect is recognized, but due to unfavorable side effects such as hormone action and safety problems, especially sebum secretion suppression, prevention and treatment of acne, dandruff on the scalp,
It is not suitable to be used for long-term use such as cosmetics which is effective in preventing itching and hair loss.

[0006]

DISCLOSURE OF THE INVENTION The present invention provides a highly safe anti-androgen agent having no hormone-like action.

[0007]

The anti-androgen agent of the present invention is characterized by using as an active ingredient an extract of the xylem of a plant of the genus Scutellaria (scientific name: Diospyros spp.) Of the family Scutellariae.

It is known that the fruits or leaves of these plants are used medicinally for the purpose of antipyretic and disinfecting wounds, but the medicinal use of xylem is not known. this time,
It was found that it has a 5α-reductase activity inhibitory action and an androgen receptor binding inhibitory action.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION Examples of the plant of the genus Scutellaria include, for example,
The following can be used: Hong Kokutan (Scientific name: Diospiros evenum Di
ospyros ebenum) Scribble (scientific name: Diospirus discolor Dio
oyster (scientific name: Diospyros oyster Diospyro)
s Kaki) Alvar Koktan (scientific name: Diospyros assimilis) Ryukyu mamegaki (scientific name: Diospyros japonica) Ryukyu oyster (scientific name: Diosspirus marichos)
Diospyros maritima Tokiwagaki (scientific name: Diospyros moriciana Di
ospyros morrisiana)

The extract of the present invention can be obtained by solvent extraction of dried or crushed xylem of a plant, and the extract may be used as it is, or may be used as a diluent or as a concentrated extract. Alternatively, it may be made into a dry powder by freeze-drying or the like, or may be prepared as a paste.

Solvent extraction is carried out by using alcohols such as methanol, ethanol and butanol, aliphatic hydrocarbons such as hexane, heptane and cyclohexane, esters such as ethyl acetate, ketones such as acetone or water alone or in combination. It is possible, and the extraction treatment is usually performed at a temperature of about 3 to 70 ° C.

The anti-androgen agent of the present invention is safe and effective for the treatment of various diseases which are considered to be caused by excessive activity of androgen, such as androgenetic alopecia, acne and benign prostatic hypertrophy. It can also be used as a cosmetic for acne prevention and hair. The dosage form of the anti-androgenic agent of the present invention can be an internal preparation such as tablets, capsules, powders, oral liquids, fine granules and granules, and also liniments, sprays, lotions,
It can also be made into a skin agent such as an ointment.

[0013]

INDUSTRIAL APPLICABILITY The anti-androgen agent of the present invention has no hormone-like action, has a high anti-androgen activity, and is useful for the prevention and treatment of various androgen-related diseases. It is used in a wide range of applications such as cosmetics.

[0014]

[Examples] Example 1 10 times amount (w /
Add 30% (v / v) aqueous ethanol solution of v) at 40 ° C.
In a water bath for 2 hours. The extract was filtered, ethanol was removed, and the extract was freeze-dried to obtain the extract shown in Table 1.

[0015]

[Table 1] Table 1: List of Extracted Samples Extracted Sample Weight (g) Extracted Extract Weight (g) Hongkotan 23.2 0.34 Kaki 21.0 1.44 Oyster 20.1 1.24 Marbar Kotan 5.7 0.29 Ryukyu Megamega 5.3 0.28 Ryukyu Gaki 5.4 0.26 Tokiwagaki 5.6 0.27

Test Example 1: Effect of inhibiting binding between androgen receptor and DHT This test was carried out by the method of Takayasu et al. (J. Steroy).
d Biochem. Vol. 19 pll41-11
46, 1983).

(1) Preparation of Androgen Receptor Solution Wistar male rats (12 weeks old) were castrated, and
After a lapse of time, the prostate was removed, and 50 mM Tris-HCl buffer (pH 7.4), 1.5 mM ethylenediaminetetraacetic acid,
After homogenizing with a 4-fold (w / v) solution containing 1 mM dithiothreitol, 10 mM sodium molybdate and 10% (w / v) glycerol, 700
The supernatant obtained by centrifuging at × g for 10 minutes at 4 ° C was collected. This supernatant was further centrifuged at 105,000 × g at 4 ° C. for 1 hour to obtain a supernatant, which was used as an androgen receptor solution.

(2) Measurement of Androgen Receptor Binding Inhibitory Activity 1 nM [ ³ H] DHT (100 Ci / mmol) and 40
Add 4 nl of a mixed solution of 0 nM-DHT, the receptor solution according to the above item (1), and specimen samples of various concentrations (total volume 250 μl).
After incubating at 16 ° C. for 16 hours, 5% (w / v) activated carbon and 0.5% (w / v) dextran (molecular weight 6
250 μl of a solution containing 0000 to 90,000) was added and centrifuged at 4 ° C. for 10 minutes to obtain a supernatant. This supernatant 2
After taking 00 μl and mixing with liquid scintillation cocktail, the specific binding amount of [ ³ H] DHT to the receptor was measured using a liquid scintillation counter.
Find the inhibition rate more.

[0019]

[Equation 1] B CONT: Receptor and [ ³ H] when sample is not added
Specific binding amount of DHT B SAMPLE: Receptor and [ ³ H] when sample is added
Specific binding amount of DHT

All specimen samples are 0.05% (w /
The concentration of v) was adjusted. The results are shown in Table 2.

[0021]

[Table 2]

Test Example 2: 5α-reductase activity inhibitory effect (1) Preparation of 5α-reductase solution Wistar male rats sacrificed by cervical dislocation (1
2 weeks old) prostate is removed, 50 mM Tris-HCl buffer (pH 7.4), 1.5 mM ethylenediaminetetraacetic acid,
After homogenizing with a 5 volume (w / v) solution containing 1 mM dithiothreitol, 10 mM sodium molybdate and 10% (w / v) glycerol, 700
The supernatant obtained by centrifuging for 10 minutes at 4 ° C. was used as an enzyme solution.

(2) Measurement of 5α-reductase inhibitory activity [ ³ H] testosterone (2 μCi) 10 μl, 3.3
150 μl of mM NADPH (nicotinamide adenine dinucleotide phosphate reduced type) solution, 100 μl of specimen samples of various concentrations and 250 μl of the enzyme solution obtained in (1) were added and shaken at 37 ° C. Then, 2 ml of a mixed solution of chloroform / methanol (2/1) was added to stop the reaction, and 700
The extract was separated by centrifugation at 10 ° C xg for 10 minutes. The peak areas of testosterone and its metabolites (DHT, androstanediol) of this extract are measured with a thin-layer chromatographic scanner, and the inhibition rate is calculated from the following equation 2.

[0024]

[Equation 2]

All specimen samples are 0.05% (W /
V) was prepared and used. The results are shown in Table 3.

[0026]

[Table 3]

A cosmetic having an excellent effect of suppressing sebum secretion was prepared by the following formulation. All percentages are by weight.

Example 2 Lotion glycerin monostearate 1.0% isopropyl palmitate 3.0% lanolin 1.0% glycerin 5.0% paraoxybenzoic acid methyl ester 0.1% stearyl cholaminoformylmethylpyridinium chloride 1.5% honkoktan extract 0.5% fragrance, pigment Trace water balance 100.0%

Example 3 Emulsion Glyceryl ether 1.5% Polyoxyethylene (20) hydrogenated castor oil 1.5% Sorbitan monostearate 1.0% Squalane 10.0% Dipropylene glycol 5.0% Keyaki extract 0.5% Perfume Trace water remaining 100.0%

Example 4 Ointment Solid paraffin 10.0% Bee wax 10.0% Squalane 10.0% Salicylic acid 0.3% Zinc white 0.5% Oyster extract 0.5% Fragrance Trace amountVaseline leftover  100.0% in total

Example 5 Hair Tonic Ethanol 59.0% Glycerin 5.0% Salicylic Acid 0.3% Distearyldimethylammonium Chloride 1.0% Marval Cocotan Extract 0.6% Fragrance 0.5% Water Residual 100.0%

Example 6 Hair rinse Stearyl dimethylbenzyl ammonium chloride 2.0% Polyoxyethylene cetyl ether 1.2% Polyoxyethylene lanolin ether 3.0% Propylene glycol 5.0% Citric acid 0.1% Sodium citrate 0.1% Butyl paraoxybenzoate 0.05% Paraoxybenzoic acid Methyl 0.1% Ryukyu Megachim Extract 0.4% Fragrance 0.2% Water Residual 100.0%

Example 7 Hair Shampoo Lauryl Sulfate Triethanolamine 15.0% Lauryl Sulfate Monoethanolamide 5.0% Magnesium Stearate 1.5% Liquid Lanolin 1.0% Propylene Glycol Monostearate 1.25% Ryukyu Ginger Extract 0.6% Fragrance, Pigment 0.2% Water balance 100.0%

Example 8 Antiperspirant Aluminum chlorohydroxide 20.0% Propylene glycol 5.0% Ethanol 10.0% Bactericide 0.2% Tokiwa extract extract 0.6% Perfume 0.2% Water balance 100.0%

Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location A61K 7/48 9051-4C

Claims (1)

[Claims] 1. An anti-androgen agent comprising an extract of the xylem of a plant belonging to the genus Scutellariae of the family Scutellariae as an active ingredient.