JPH0570360A - Androgenic hormone-resistant agent - Google Patents

Abstract

PURPOSE:To provide the subject safe agent containing the extract of at least one plant selected from Japanese galenicals, Chinese galenicals and galenicals produced in Peru as an active ingredient, effective for the inhibition of sebum secretion, the prevention and treatment of acne, the prevention of dandruff, itch and alopecia, etc., and not having a hormone-like activity. CONSTITUTION:An and androgenic hormone-resistant agent contains the extract of a galenical selected from eight kinds of Japanese and Chinese galenicals consisting of Malva sylvestris, Leonurus heterephyllus, Acctium lappa, Calendula arvensis, Chelidonium majus, Gleditschia japonica, SANSHISHI and Osmanthus fragrans, and 14 kinds of Peru galenicals consisting of Lippia triphylla, Cymbopogon citratrus, Chichorium intybus, Piper elongatum, Argemone mexicana, Urens Jacq., Phyllanthus niruri, Minthostachys setosa, Atachys bogotensis, Sapindus saponaria, Bauhinia aculeata, Amarantus sp., Prosopis cilensis, and Chysanthemum parthenium as an active ingredient. The agent is useful for preventing and treating various diseases related with androgenic hormones, and used for a wide range of uses such as medicines and cosmetics.

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

However, if the 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 considered that the increase in sebum secretion is caused by the hyperactivity of male hormones. In addition to this, from the past,
Hypertension, acne, seborrhea, benign prostatic hyperplasia, prostate tumor and the like are known as diseases in which male hormones are involved, and all are considered to be caused by excessive activity of male hormones. 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 its effect is recognized, but because of its unfavorable side effects such as hormone action and safety problems, in particular, sebum secretion suppression, prevention and treatment of acne, dandruff on the scalp,
It is not suitable for blending into long-term products such as cosmetics which are 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 in that it contains at least one extract selected from the following plants (1) to (22) as an active ingredient. Among these, (1) to (8) are Japanese and Chinese herbs, which mainly have an inhibitory effect on androgen receptor binding. Further, (9) to (22) are Peru-producing drugs, which have a 5α-reductase inhibitory action and an androgen receptor binding inhibitory action.

(1) Common mallow (2) Yakusou (3) Burdock (4) Calendula (5) Magnolia (6) Psychic (7) Sanshishi (8) Antler

(9) Cedron (scientific name: Lipia triphyra; Lippia triphy
lla) (10) Hierba Luis
a) (Scientific name: Cymbopogon citrus); Cymb
opogon citrus)

(11) Achicoria
a) (Scientific name: Cichorium intibus; Chicho
riam intybus) (12) Matico (scientific name: Piper elongatum)

(13) Cardo Santo
Santo) (Scientific name: Argemone Mexicana; Arg
(Emone mexicana) (14) Ortiga negra
ra) (Scientific name: Urens Jacq.)

(15) Chanka Piedra
apiedra) (scientific name: Phalantas niluri; Ph
yllanthus niruri (16) Muna (scientific name: mintstachys
Setosa; Minthostachys setosa)

(17) Asnac-Kora (Asnac
-Ccora) (scientific name: Attachys bogote
(18) Coloque (scientific name: Sapindus saponaria; Sapindus sapona)
ria)

(19) Una de Gato
gato) (Scientific name: Bowhinia Actor; Bau
(20) Kiwicha (scientific name: Amarantus sp.)

(21) Algarrob
o) (Scientific name: Prosopis sirensis; Prosopi
s cilensis (22) Manzanilla (scientific name: Chrysanthemum parthenium; Chrysant)
hemum parthenium)

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION The extract of the present invention is obtained by subjecting a plant to a dry or crushed product and subjecting it to solvent extraction. 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, benign prostatic hyperplasia and the like. It can also be used as a cosmetic for preventing acne and for hair.

The anti-androgen of the present invention can be used in the form of tablets, capsules, powders, oral liquids, fine granules, granules, etc., and also liniments, sprays, lotions. It can also be used as an external skin agent such as an agent or an ointment.

[0020]

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.

[0021]

【Example】

Example 1 10 g of dried shredded mallow, 10 g of dried yamwort shredded, 20 g of dried burdock shredded, 10 g of dried calendula shredded, 10 g of dried shredded shredded, 10 g of dried shredded shredded, dried shredded shredded 20g, dried ginseng shredded matter 10g, 10 times amount (w / v) of 3
A 0% (v / v) ethanol aqueous solution was added, and the mixture was extracted for 2 hours in a water bath at 50 ° C. Next, the mixture was filtered, ethanol was removed, and then freeze-dried to obtain the following extract extracts.

Scutellaria asiatica extract 1.008 g Yakusou extract 0.519 g Burdock extract 1.699 g Calendula extract 2.641 g Kanoshino extract 2.158 g Psychic extract 2.149 g Sardine extract 2.436 g Ginseng extract 2.518 g

Test Example 1: Effect of inhibiting binding between androgen receptor and DHT This test is 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 to give 24
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 resulting supernatant was collected by centrifugation at × g for 10 minutes at 4 ° C. 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 a specimen sample 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.

[0026]

[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
Table 1 shows the results of the specific binding amount of DHT.

[0027]

[Table 1] Table 1: Androgen Receptor Binding Inhibitory Activity Test Sample Concentration (μm / ml) Inhibition Rate (%) Scutellaria baicalensis Extract Extract 100 53.1 Yakusoma Extract Extract 500 26.6 Burdock Extract Extract 100 33.8 Calendula Extract 500 26.3 Kusanou Extract Extract 500 16.8 Ringworm extract Extract 500 19.8 Sanshishi extract Extract 500 20.2 Ginkgo biloba extract 500 13.8

Example 2 10 g of each dried herb shredded product was mixed with 10 times amount (w / v) of 3 each.
A 0% (v / v) ethanol aqueous solution was added, and the mixture was extracted for 2 hours in a water bath at 50 ° C. Then, the mixture was filtered, ethanol was removed, and then freeze-dried to obtain the extract as follows.

Cedron Extract 1.082g Hierba Luisa Extract 1.564g Achicoria Extract 2.001g Matico Extract 1.836g Cardo Santo Extract 2.755g Ortiga Negra Extract 1.969g Chancapiedra Extract 1.020g Muna Extract 1.4576g Ucora Extract. gato extract 1.777g Kiwicha extract 2.560g Algarrobo extract 1.598g Manzanilla extract 1.620g

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 homogenization 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 centrifuging at ℃ × g for 10 minutes. The peak area of testosterone and its metabolites (DHT, androstanediol) of this extract is measured with a thin-layer chromatographic scanner, and the inhibition rate is calculated from the following equation 2.

[0032]

[Equation 2] The results are shown in Table 2.

[0033]

[Table 2] Table 2: 5α-reductase activity inhibitory test substance Concentration (%) Inhibition rate (%) Cedron extract 0.1 44.0 Yerba Luisa extract 0.1 38.0 Atticoria 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 Chanka Piedra Extract 0.1 15.6 Muna Extract 0.1 19.0 Aznak-Kola Extract 0.1 31.3 Coloke Extract 0.1 9.5 Una de Gato Extract 0.1 44.0 Kiwicha Extract 0.1 4.8 Arugalobo 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: Androgen receptor binding inhibitory effect Test substance concentration (μm / ml) Inhibition rate (%) Cedron extract 500 25.2 Yerba Luisa extract 500 26.9 Aticoria extract 500 16.2 Machico extract 500 60.3 Cardo Santo extract 500 13.4 Ortiga Negra Extract 500 13.0 Chanka Piedra Extract 500 22.0 Muna Extract 500 23.1 Aznak-Kola Extract 500 19.8 Coloke Extract 500 25.6 Una De Gato Extract 500 15.2 Kiwicha Extract 500 14.3 Arugalobo Extract 500 27.6 Manzanilla Extract 100 17.5

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

Example 3 Toner lotion Glycerin monostearate 1.0% Isopropyl palmitate 3.0% Lanolin 1.0% Glycerin 5.0% Paraoxybenzoic acid methyl ester 0.1% Stearyl colaminoformylmethylpyridinium 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 amount of water 100.0%

Example 5 Ointment Solid paraffin 10.0% Beeswax 10.0% Squalane 10.0% Salicylic acid 0.3% Zinc white 0.5% Chanka piedra extract 0.1% Muna extract 0.2% Aznak-cola extract 0.2% Fragrance Trace petrolatum Residual 100.0%

Example 6 Hair Tonic Ethanol 59.0% Glycerin 5.0% Salicylic acid 0.3% Distearyldimethylammonium chloride 1.0% Coloke 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 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% Arugalobo extract 0.2% Manzanilla extract 0.2% Fragrance 0.2% Water balance 100.0%

Example 8 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% Cedron Extract 0.3% Machico Extract 0.2% Muna Extract 0.1% Fragrance, Dye 0.2% Water balance 100.0%

Example 9 Antiperspirant Aluminum chlorohydroxide 20.0% Propylene glycol 5.0% Ethanol 10.0% Bactericide 0.2% Athikoria extract 0.2% Machiko extract 0.2% Coloke extract 0.2% Perfume 0.2% Water balance 100.0%

Claims (1)

[Claims] Claims: 1. Alveolus, Yakusou, Burdock, Calendula, Limbo, Ginkgo, Sanshishi, Ginkgo sardines, Cedron, Yerba Luisa, Athikoria, Machiko, Cardo Santo, Ortiga Negra, Chankapiedra, Muna, Aznak-Kora, Koroke, Koroke, Koroke. An anti-androgen agent comprising, as an active ingredient, an extract of at least one plant selected from Una de Gato, Kiwicha, Argarovo and Manzanilla.