JP3165832B2 - Antiandrogens - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an antiandrogen using a plant extract.

[0002]

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

However, when its secretion is excessive, it becomes sticky and easily stained, and the pathogenic bacteria easily propagate. Seborrhea, acne, dandruff and itching in the scalp, and male pattern baldness are all due to increased sebum secretion.

[0004] Increased sebum secretion is thought to be caused by excessive activity of male hormones. In addition to this,
Known disorders involving androgen include hirsutism, androgenetic alopecia, acne, seborrhea, benign prostatic hyperplasia, and prostate tumors, all of which are thought to be caused by excessive androgen activity. I have. In particular, various studies have revealed that 5α-dihydrotestosterone (DHT), a metabolite of testosterone, is responsible for the disease. Various antiandrogens have been used to treat these diseases, for example, inhibiting the activity of 5α-reductase, which reduces testosterone to highly bioactive DHT in target organs, or This is due to inhibiting the binding between the generated DHT and the receptor in the target cell.

[0005] However, these antiandrogens such as cyproterone acetate, oxendrone,
Chlormadinone acetate and the like are steroid hormone derivatives, but their effects are recognized, but they have undesirable side effects such as hormonal action and have safety problems.In particular, sebum secretion suppression, prevention and treatment of acne, dandruff in the scalp,
It is not suitable to be used for long-term use such as cosmetics effective for preventing itching and hair loss.

[0006]

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

[0007]

The antiandrogenic agent of the present invention is a legume belonging to the genus Microberlin.
inia spp. , No Japanese name of the genus, Inuenju (scientific name: Macchia spp. Macackia sp.)
p. ) Guibourtiasp
p. , No Japanese name of the genus), Leguminosae tagayasan (scientific name: Cassia siamea; Cassia siam)
ea) and Yamahagi (scientific name: Lespedeza bicala; L
and at least one plant xylem or leaf extract selected from Espedeza bicolor) as an active ingredient.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION As a plant of the genus Microberlinina,
For example, the following can be used. Zebrawood (scientific name: Microberlinia brazzavinis; Microberlinia brazzavi
llensis) Zingana (scientific name: Micro Bell Linear Bislucata; M)
(microberlinia bisulcata)

[0009] As the plants of the genus Inuju, for example, the following can be used. Shimaenju (scientific name: Makia Tashiloi Macchi
a tashiroi) Hanemiinuenju (scientific name: Macchia floribunda Maackia floribu)
nda) Carainenju (scientific name: Macchia amrensis Ma
ackia amurensis Inouenju (scientific name: Macia amrensis bar
Buergeri Macchia amurensis
var. bugereri) Macchia sinensis Maackia chinens
is (no Japanese name) Ma Kuraki (scientific name: Machia Hupehensis Maackia
huphensis)

As the plants of the genus Guibolthia, for example,
The following can be used: Bubanga (scientific name: Guiboltia Tesmanii Gu
ibourtia tessmannii Musi (scientific name: Guiboltia Coleosperma Gui)
bourtia coleosperma Congo copalnoki (scientific name: Guiboltia demeusii) Anoki (scientific name: Guiboltia ehei Guibo)
ultia ehie)

In addition to the above-mentioned leguminous plants, an extract of Yamahagi of the genus Lepedeza spp. And Tagayasan of the genus Cassia spp. Of the legume family can also be used in the present invention.

The extract of the present invention can be obtained by subjecting a plant body to dryness or pulverization as it is, followed by solvent extraction. The extract may be used as it is, or may be used as a diluent or as a concentrated extract. Alternatively, the powder may be prepared as a dry powder by freeze-drying or the like, or may be prepared in a paste form. As plants, xylem and leaves can be used,
Wood and leaves are preferably used in Yamahagi, and wood is used in other plants.

The solvent extraction is carried out by using an alcohol such as methanol, ethanol and butanol, an aliphatic hydrocarbon such as hexane, heptane and cyclohexane, an ester such as ethyl acetate, a ketone such as acetone or water alone or as a mixture. The extraction is usually performed at a temperature of about 3 to 70 ° C.

The antiandrogen of the present invention is safe and effective for the treatment of various diseases which are thought to be caused by excessive androgen activity, for example, androgenetic alopecia, acne, prostatic hypertrophy and the like. It can also be used as a cosmetic for acne prevention and for hair. As the dosage form of the antiandrogen of the present invention, tablets, capsules, powders, internal liquids, fine granules, can be made into internal preparations such as granules, also liniment, spray, lotion,
It can also be used as a skin preparation such as an ointment.

[0015]

Industrial Applicability The antiandrogen of the present invention has no hormone-like action, has high antiandrogen activity, is useful for the prevention and treatment of various diseases involving androgen, It is used for a wide range of applications such as cosmetics.

[0016]

【Example】

Example 1 For each amount of dried xylem shredded material (in the case of zebrawood, tagayasan, carainengju and bubanga) or dried xylem and leaf shredded material (in the case of Yamahagi) shown in Table 1,
A 0-fold (w / v) 30% (v / v) aqueous ethanol solution was added, and the mixture was extracted in a 40 ° C water bath for 2 hours. The extract was filtered, ethanol was removed, and then lyophilized to obtain extract extracts shown in Table 1.

[0017]

[Table 1] Table 1: List of extracted samples Weight of extracted sample shreds (g) Weight of extracted extract (g) Zebrawood 6.6 0.10 Tagayasan 5.0 0.29 Carainengje 5.3 0.11 Bubanga 5.0 0.23 Yamahagi 20.6 0.86

Test Example 1: Binding inhibitory effect between androgen receptor and DHT This test was carried out by the method of Takayasu et al.
d Biochem. Vol. 19 pll41-11
46, 1983).

(1) Preparation of androgen receptor solution Wistar male rats (12-week-old) were castrated.
After time, the prostate was removed and 50 mM Tris-HCl buffer (pH 7.4), 1.5 mM ethylenediaminetetraacetic acid,
After homogenizing with a 4 volume (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. The 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 mM
A mixed solution (250 μl in total volume) of 0 nM-DHT, the receptor solution according to the above item (1), and sample samples of various concentrations was prepared.
After incubation at 16 ° C. for 16 hours, 5% (w / v) activated carbon and 0.5% (w / v) dextran (molecular weight 6
0000-90000) and centrifuged at 4 ° C. for 10 minutes to obtain a supernatant. This supernatant 2
After taking 00 μl and mixing with the liquid scintillation cocktail, the amount of specific binding of [ ³ H] DHT to the receptor was measured using a liquid scintillation counter.
Obtain the inhibition rate more.

[0021]

(Equation 1) B CONT: receptor and [ ³ H] when no sample was added
Specific binding amount of DHT B SAMPLE: Receptor and [ ³ H] when sample was added
Specific binding amount of DHT

Each of the test samples was 0.05% (w /
It was adjusted to the concentration of v). Table 2 shows the results.

[0023]

[Table 2]

Test Example 2: Inhibitory effect of 5α-reductase activity (1) Preparation of 5α-reductase solution Wistar male rat (1) prepared by cervical dislocation
(2 weeks old), the prostate was removed, and 50 mM Tris-HCl buffer (pH 7.4), 1.5 mM ethylenediaminetetraacetic acid,
After homogenizing with a 5-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 used as an enzyme solution.

(2) Measurement of 5α-reductase inhibitory activity [ ³ H] testosterone (2 μCi) 10 μl, 3.3
150 μl of an mM NADPH (nicotinamide adenine dinucleotide phosphate-reduced) solution, 100 μl of a sample sample having various concentrations, and 250 μl of the enzyme solution obtained in the section (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.
The extract was separated by centrifugation at xg for 10 minutes. The peak area of testosterone and its metabolites (DHT, androstanediol) is measured for this extract using a thin-layer chromatograph scanner, and the inhibition rate is calculated by the following equation (2).

[0026]

(Equation 2) All sample samples were prepared and used at a concentration of 0.05% (W / V). Table 3 shows the results.

[0027]

[Table 3]

A cosmetic having an excellent sebum secretion inhibitory effect was prepared according to the following formulation. All percentages are based on weight.

Example 2 Lotion Glycerin Monostearate 1.0% Isopropyl Palmitate 3.0% Lanolin 1.0% Glycerin 5.0% Paraoxybenzoic acid methyl ester 0.1% Stearylcholaminoformylmethylpyridium chloride 1.5% Zebrawood extract 0.5% Fragrance, Pigment trace water remaining 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% tagayasan extract 0.5% fragrance trace water remaining 100.0%

Example 4 Ointment solid paraffin 10.0% beeswax 10.0% squalane 10.0% salicylic acid 0.3% zinc white 0.5% carrageenju extract 0.5% fragrance trace amount petrolatum balance 100.0%

Example 5 Hair tonic Ethanol 59.0% Glycerin 5.0% Salicylic acid 0.3% Distearyl dimethyl ammonium chloride 1.0% Bubunga extract 0.6% Fragrance 0.5% Water balance 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% Yamahagi extract 0.4% Fragrance 0.2% Water balance 100.0%

Example 7 Hair Shampoo Triethanolamine Lauryl Sulfate 15.0% Lauryl Sulfate Monoethanolamide 5.0% Magnesium Stearate 1.5% Liquid Lanolin 1.0% Propylene Glycol Monostearate 1.25% Zebrawood Extract 0.2% Bubanga Extract 0.2% Kara Dog extract extract 0.2% Fragrance, pigment 0.2% Water balance 100.0%

Example 8 Antiperspirant Aluminum chlorohydroxide 20.0% Propylene glycol 5.0% Ethanol 10.0% Fungicide 0.2% Tagayasan extract 0.3% Yamahagi extract 0.3% Fragrance 0.2% Water balance 100.0%

Continuation of the front page (51) Int.Cl. ⁷ identification code FI A61P 17/14 A61P 17/14 (56) References JP-A-61-238719 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 35/78 A61K 7/00 A61K 7/06 A61P 5/28 A61P 17/14 BIOSIS (DIALOG) CA (STN) MEDLINE (STN)

Claims (1)

(57) [Claims] 1. An extract comprising at least one plant xylem or leaf extract selected from the legumes Microberlinia, Innugenus, Guiboltia, legumes Tagayasan and Yamahagi as an active ingredient. Anti-androgens.