JP3177642B2 - 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.

[0003] 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,
As diseases involving androgens, hirsutism, acne, seborrhea, benign prostatic hyperplasia, prostate tumors, and the like are known, and all are considered to be caused by excessive activity of androgen. 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 characterized in that at least one extract selected from the following plants (1) to (22) is used as an active ingredient. Among them, (1) to (8) are Japanese and Chinese crude drugs, which mainly have an androgen receptor binding inhibitory action. Further, (9) to (22) are Peruvian drugs, which have a 5α-reductase inhibitory action and an androgen receptor binding inhibitory action.

[0008] (1) Usvenia oyster (2) Yakumoso (3) Burdock (4) Kusanou (5) Saikachi (6) Sanshishi (7) Oyster

(9) Cedron (Scientific name: Lipia triphylla)
lla) (10) Hierba Luis
a) (Scientific name: Simbopogon citraturus; Cymb
opogon citrurus)

(11) Achicoria
a) (Scientific name: Chicolium intives; Chicho
rium intybus) (12) Matico (scientific name: Piper elongatum)

(13) Cardo Santo (Cardo)
Santo) (Scientific name: Argemone Mexicana; Arg)
emone mexicana) (14) Ortiga neg
ra) (scientific name: Urens Jacq.)

(15) Chancapiedra
apiedra) (scientific name: Phalantus Nirli; Ph)
yillanthus niruri (16) Muna (scientific name: mint stachys)
Setosa; Minthostachys setosa)

(17) Asnac-Kora (Asnac)
-Ccora) (Scientific name: Atachis body)
nsis) (18) Choroque (scientific name: Sapindus saponaria; Sapindus sapona)
ria)

(19) Una de Gato
gato) (scientific name: Bouhinia accelerator; Bau
hinia aculeata) (20) Kiwicha (scientific name: Amarantus; Amarantus sp.)

(21) Algarrob
o) (scientific name: Prosopis silensis; Prosopi)
s cilensis) (22) Manzanilla (scientific name: chrysanthem parthenium; Chrysant)
heum parthenium)

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION The extract of the present invention is obtained by drying or pulverizing a plant body and extracting it with a solvent. This 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 in a paste form.

The solvent extraction is carried out by using an alcohol such as methanol, ethanol, butanol, an aliphatic hydrocarbon such as hexane, heptane, 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 treating various diseases which are considered to be caused by excessive androgen activity, for example, male pattern baldness, acne, prostatic hypertrophy and the like. It can also be used as a cosmetic for acne prevention and for hair.

The dosage form of the antiandrogenic agent of the present invention can be made into tablets, capsules, powders, oral liquids, fine granules, granules, and the like, and also liniments, sprays, lotions and the like. Agents, ointments and the like.

[0020]

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.

[0021]

【Example】

Example 1 10 g of a dried shrimp cut mushroom, 10 g of a dried mung beetle shred, 20 g of a dried burdock shrimp, 10 g of a dried calendula shred, 10 g of a dried cynosperm shred, 10 g of a dried locust shred, 10 g of a dried sashimi 10 g (w / v) of 3 per 20 g and 10 g of dried Chinese cinnamon shreds
A 0% (v / v) aqueous ethanol solution was added, and the mixture was extracted in a 50 ° C water bath for 2 hours. Next, the mixture was filtered, ethanol was removed, and then lyophilized to obtain the following extracted extracts.

Usvenia mallow extract 1.008 g Yakumoso extract 0.509 g Burdock extract 1.699 g Kusanou extract 2.158 g Hoy locust extract 2.149 g Sanshishi extract 2.436 g Kinmokusei extract 2.518 g

Test Example 1: Effect of Inhibiting Binding of Androgen Receptor to DHT This test was carried out according to 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
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.

[0026]

(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 The results are shown in Table 1.

[0027]

Table 1: Table 1: Androgen receptor binding inhibitory activity test sample concentration (μm / ml) Inhibition rate (% ) Usbania mallow extract 100 53.1 Yakumosou extract 500 26.6 Burdock extract 100 33.8 Kusanou Extract extract 500 16.8 Honey cinnamon extract extract 500 19.8 Sanshishi extract extract 500 20.2 Perilla extract 500 13.8

Example 2 10 g (w / v) of 3 was added to 10 g of each dried herb shredded product.
A 0% (v / v) aqueous ethanol solution was added, and the mixture was extracted in a 50 ° C water bath for 2 hours. Next, the mixture was filtered, ethanol was removed, and then lyophilized to obtain an extract as described below.

Cedron extract 1.082 g Hierba Luisa extract 1.564 g Achicoria extract 2.001 g Matico extract 1.836 g Cardo Santo extract 2.755 g Ortigana extract 1.969 g Gato extract 1.777g Kiwicha extract 2.560g Algarrobo extract 1.598g Manzanilla extract 1.620g

Test Example 2: Inhibitory effect of 5α-reductase activity (1) Preparation of 5α-reductase solution Wistar male rats (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. Next, 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).

[0032]

(Equation 2) Table 2 shows the results.

[0033]

[Table 2] Table 2: 5α-reductase activity inhibitory effect Test sample concentration (%) Inhibition rate (%) Cedron extract 0.1 44.0 Yerba luisa extract 0.1 38.0 Aticoria extract 0.1 19.3 Machico extract 0.1 58.5 Cardo santo extract 0.1 3.5 Ortiga・ Negra extract 0.1 43.6 Chancapiedra extract 0.1 15.6 Muna extract 0.1 19.0 Azunak-Kola extract 0.1 31.3 Koroke extract 0.1 9.5 Una de Gato extract 0.1 44.0 Kiwicha extract 0.1 4.8 Argarobo extract 0.1 5.4 Manzanilla extract 0.1 43.3

Test Example 3 The androgen receptor binding inhibitory activity was measured in the same manner as in Test Example 1, and the results are shown in Table 3.

[0035]

[Table 3] Table 3: Inhibitory Effect of Androgen Receptor Binding Test Sample Concentration (μm / ml) Inhibition Rate (%) Cedron Extract 500 25.2 Yerba Luisa Extract 500 26.9 Aticolia Extract 500 16.2 Machiko Extract 500 60.3 Cardo Santo Extract 500 13.4 Ortiga Negra extract 500 13.0 Chancapiedra extract 500 22.0 Muna extract 500 23.1 Aznac-Kola extract 500 19.8 Koroke extract 500 25.6 Una de Gato extract 500 15.2 Kiwicha extract 500 14.3 Argarobo extract 500 27.6 Manzanilla extract 100 17.5

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

Example 3 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% Cedron extract 0.1% Yerba Luisa extract 0.2% Achikoria extract 0.2% Fragrance, pigment Trace water remaining 100.0%

Example 4 Emulsion Glyceryl ether 1.5% Polyoxyethylene (20) hydrogenated castor oil 1.5% Sorbitan monostearate 1.0% Squalane 10.0% Dipropylene glycol 5.0% Machiko extract 0.1% Cardo Santo extract 0.2% Ortiga negra extract 0.2 % Fragrance trace water remaining 100.0%

Example 5 Ointment Solid paraffin 10.0% Beeswax 10.0% Squalane 10.0% Salicylic acid 0.3% Zinc white 0.5% Chancapiedra extract 0.1% Muna extract 0.2% Aznac-Kola extract 0.2% Fragrance Trace amount petrolatum Balance 100.0%

Example 6 Hair tonic Ethanol 59.0% Glycerin 5.0% Salicylic acid 0.3% Distearyl dimethyl ammonium chloride 1.0% Coroque extract 0.2% Una de Gato extract 0.2% Kiwicha extract 0.2% Fragrance 0.5% Water balance 100.0%

Example 7 Hair rinse Stearyl dimethyl benzyl 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% Argarobo extract 0.2% Manzanilla extract 0.2% Fragrance 0.2% Water balance 100.0%

Example 8 Hair shampoo 15.0% triethanolamine lauryl sulfate 5.0% lauryl monoethanolamide 5.0% Magnesium stearate 1.5% Liquid lanolin 1.0% Propylene glycol monostearate 1.25% Cedron extract 0.3% Machico extract 0.2% Muna extract 0.1% Fragrance, Dye 0.2% Water balance 100.0%

Example 9 Antiperspirant Aluminum Chloride 20.0% Propylene Glycol 5.0% Ethanol 10.0% Fungicide 0.2% Aticolia Extract 0.2% Machiko Extract 0.2% Koroke Extract 0.2% Fragrance 0.2% Water Balance 100.0%

──────────────────────────────────────────────────の Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) A61K 35/78 A61K 7/06 A61P 5/28 A61P 17/14 BIOSIS (DIALOG) CA (STN) MEDLINE (STN) )

Claims (1)

(57) [Claims] (1) Usvenia oyster, Yakumoso, Burdock
Cities, districts Sanoou, honey locust, Sanshishi, osmanthus,
Extract of at least one plant selected from Cedron, Yerba Luisa, Atikoria, Machiko, Cardo Santo, Ortiga Negra, Chancapiedra, Muna, Aznak-Kola, Koroke, Una de Gato, Kiwicha, Algarrobo and Manzanilla An anti-androgen, comprising as an active ingredient.