JPH10139680A - Anti-androgens - Google Patents

Abstract

(57) [Summary] [Problem] Akaku, Angelim da Mata, Sedro, Sedro Loxo, Koataquikaua, Kumar, Faeira, Faba Amargoza, Faba Japakanim, Inga Tete, Jacaranda, Louro Fire, Makakauba, Mogno , Muira Piranga, Pau Amarello, Pau
An antiandrogen comprising as an active ingredient at least one plant extract selected from darco, prauba, skupira and sukupira amarella. SOLUTION: This is an anti-androgen having excellent anti-androgen activity and high safety when applied to the human body, and can be used for various uses such as pharmaceuticals, quasi-drugs, and cosmetics. it can.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD 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 soiled, and it becomes easy for pathogenic bacteria to propagate. Seborrhea, acne, dandruff and itching in the scalp, and male pattern baldness are all due to increased sebum secretion. Increased sebum secretion is thought to be caused by excessive androgen activity. In addition to these, hirsutism, benign prostatic hyperplasia, prostate tumor, and the like have been known as diseases in which androgens are involved, all of which are considered to be caused by excessive male hormone activity. 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, and their effects include, for example, 5α, which reduces testosterone to highly bioactive DHT in target organs.
-Inhibit the activity of reductase or produce DH
It is by inhibiting the binding of T to the receptor in the target cell.

Conventional antiandrogens, for example, cyproterone acetate, oxendrone, chlormadinone acetate, etc. are steroid hormone derivatives, so they have an effect, but have undesirable side effects such as hormonal action.
Due to safety issues, it is particularly suitable to be used for long-term use, such as cosmetics that are effective in suppressing sebum secretion, preventing and treating acne, and preventing dandruff, itching and hair loss on the scalp. There was no problem.

[0004] In view of the above, the development of antiandrogens having excellent antiandrogenic activity and having high safety when applied to the human body is expected.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide an antiandrogen having excellent antiandrogenic activity and excellent safety.

[0006]

The antiandrogen of the present invention is characterized in that at least one extract selected from the following Brazilian drugs (1) to (20) is used as an active ingredient. . (1) Acucu (scientific name: Hura cre)
pitans) (2) Angelim da Mata (Angelim da)
data) (scientific name: Hymenolobium pet)
raeum) (3) Cedro (scientific name: Cedrela)
odorata) (4) Cedro roxo (scientific name: Cedella fissilis) (5) Coataquicaua
(Scientific name: Peltogyne paniculata) (6) Kumaru (scientific name: Diptery)
x odorata) (7) Faeira (scientific name: Roupa)
la montana) (8) Faba amargos
a) (Scientific name: Vataireopsis specio)
sa) (9) Faba japacanim
nim) (scientific name: Parkia gigantocar)
pa) (10) Inga tete (scientific name:
Inga paraensis (11) Jacaranda (scientific name:
Dalbergia sp. (12) Louro faia
(Scientific name: Euplasspinnata) (13) Macacauba (scientific name: P
(14) Mogno (Scientific name: Sweeten)
ia macrophylla) (15) Muirapiranga
(Scientific name: Brosimum rubescens) (16) Pau amarero
(Scientific name: Exylophora paraensi
s) (17) Pau d'arco (scientific name: Tabebuia serratifolia) (18) Pracuuba (scientific name: Tr)
(19) Sucupira (scientific name: Dip)
lotropis purpurea (20) Supupira amarera
arela) (scientific name: Bowdichia nitid)
a)

[0007] The extract of the present invention can be 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 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.

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 used safely and effectively in the treatment of 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.

[0010] The dosage form of the antiandrogen of the present invention is arbitrary, and can be made into a dosage form suitable for oral administration such as tablets, capsules, powders, oral liquids, fine granules, granules and the like. ,
A dosage form suitable for a skin external preparation such as a liniment, a spray, a lotion, an ointment and the like can be used, and can be used as any dosage form.

When used as an external preparation for skin, the plant extract, which is an essential component, can be blended at any concentration.
Usually, it is admixed with 0.01 to 30% by weight, preferably 0.1 to 10% by weight in various skin external preparations.

In addition to the above essential components, the skin external preparation containing the plant extract of the present invention contains, in addition to the above-mentioned essential components, raw materials usually used in skin external preparations, such as surfactants, oils, alcohols, humectants, and thickeners. Agents, preservatives, antioxidants, chelating agents, pH adjusters, fragrances, pigments, ultraviolet absorbers / scatterers, vitamins, amino acids, water and the like.

More specifically, as the surfactant, lipophilic glycerin monostearate, self-emulsifying glycerin monostearate, polyglycerin monostearate, sorbitan monooleate, polyethylene glycol monostearate are used as nonionic surfactants. Ester type such as polyoxyethylene sorbitan monooleate, ether ester type such as polyoxyethylene hydrogenated castor oil, polyoxyethylene cetyl ether, polyoxyethylenated sterol, polyoxyethylenated lanolin,
Ether type such as polyoxyethylenated beeswax can be exemplified. Examples of the anionic surfactant include a carboxylate type, a sulfonate type, a sulfate ester type and a phosphate ester type. Examples of the carboxylic acid type include higher fatty acid salts such as sodium stearate, potassium palmitate and triethanolamine palmitate; N acyl such as N lauroyl N methyl glycine sodium, N myristyl N methyl β-alanine potassium, and N palmityl glutamate triethanolamine. Examples thereof include amino acid salts and alkyl ether carboxylate salts such as potassium lauryl ether carboxylate. Examples of the sulfonate type include sodium cetyl sulfonate, examples of the sulfate type include sodium lauryl ether sulfate, and examples of the phosphate type include sodium lauryl phosphate and sodium polyoxyethylene lauryl phosphate. Examples of the cationic surfactant include stearyldimethylbenzylammonium chloride and stearyltrimethylammonium chloride. Examples of the amphoteric surfactant include an alkylaminoethyl glycine chloride solution and lecithin.

The oil component includes vegetable oils such as castor oil, olive oil, cacao oil, camellia oil, coconut oil, wood wax, jojoba oil, grape seed oil, avocado oil, animal oils such as mink oil, egg yolk oil, and honey. Waxes such as wax, whale wax, lanolin, carnauba wax, candelilla wax, liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, hydrocarbons such as petrolatum, lauric acid, myristic acid, stearic acid, oleic acid , Isostearic acid, natural and synthetic fatty acids such as behenic acid, cetanol, stearyl alcohol,
Examples include natural and synthetic higher alcohols such as hexyldecanol, octyldodecanol, and lauryl alcohol; esters such as isopropyl myristate, isopropyl palmitate, isopropyl adipate, octyldodecyl myristate, octyldodecyl oleate, and cholesterol oleate. Can be.

Examples of the humectant include polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerin, polyethylene glycol and dipropylene glycol, amino acid derivatives such as trimethylglycine, sodium lactate and pyrrolidone carboxylic acid. Examples include NMF components such as sodium acid and amino acids, and water-soluble polymer substances such as hyaluronic acid, collagen, mucopolysaccharide, and chondroitin sulfate.

As the thickener, sodium alginate,
Xanthan gum, aluminum silicate, quince seed extract, tragacanth gum, natural polymer substances such as starch,
Semi-synthetic polymer substances such as methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, soluble starch, and cationized cellulose can be exemplified.

Examples of preservatives include benzoate, salicylate, sorbate, dehydroacetate, p-hydroxybenzoate, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'- Trichlorocarbanilide, benzalkonium chloride, hinokitiol,
Resorcinol, ethanol and the like can be exemplified.

Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, ascorbic acid, tocopherol, and tocotrienol. Examples of the chelating agent include disodium edetate, ethylenediaminetetraacetate, pyrophosphate, and hexametaline. Acid salts, citric acid, tartaric acid, gluconic acid, etc.
Examples of the H adjustor include sodium hydroxide, triethanolamine, citric acid, sodium citrate, boric acid, borax, potassium hydrogen phosphate, and the like.

Examples of the ultraviolet absorbing / scattering agent include 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexylparamethoxycinnamate, titanium oxide, kaolin, talc and the like.

The vitamins include vitamin A, vitamin B group, vitamin C, vitamin D, vitamin E, vitamin F, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ-oryzanol, α-lipoic acid, Orotic acids and their derivatives can be exemplified.

The amino acids include glycine, alanine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, tryptophan,
Examples thereof include cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, asparagine, glutamic acid, glutamine, arginine, histidine, lysine, and derivatives thereof.

The optional components are not limited to these. By appropriately mixing the above essential components and optional components, various skin external preparations, for example, creams, emulsions, lotions, serums, packs, shampoos, rinses,
Under makeup, foundation, jelly,
It can be used as a product form such as an ointment.

Specific examples when the antiandrogen of the present invention is used as a skin cosmetic are shown in the following (1) to (6).
It is as follows. (1) In the case of skin cream 0.1-10% by weight of plant extract, 20-70% by weight of oil, 2-7% by weight of surfactant, 1-10% by weight of humectant, trace amount of preservative, trace amount of fragrance, Skin cream containing residual amount of purified water.

(2) In the case of emulsion 0.1 to 10% by weight of plant extract, 10 to 40% by weight of oil, 0 to 15% by weight of alcohols, 1 to 5 of surfactant
Weight%, humectant 1-10% by weight, thickener 0-2% by weight,
Emulsion containing trace amounts of preservatives, trace amounts of fragrance, and residual amounts of purified water.

(3) In the case of lotions and serums 0.1 to 10% by weight of plant extract, alcohols 5
20% by weight, surfactant 0 to 2% by weight, humectant 2 to 8% by weight, thickener 0 to 2% by weight, antioxidant 0 to 0.5% by weight, chelating agent 0 to 0.1% by weight PH adjusters 0 to 0.
Lotion and serum containing 2% by weight, 0 to trace amount of pigment, trace amount of preservative, trace amount of fragrance, and residual amount of purified water.

(4) In the case of a pack agent 0.1 to 10% by weight of plant extract, alcohol 2 to
10% by weight, humectant 2-10% by weight, inorganic powder 0-20
A pack containing 10% by weight, 10-20% by weight of a film forming agent, a trace amount of preservative, a trace amount of fragrance, and a residual amount of purified water.

(5) In the case of shampoo 0.1 to 10% by weight of plant extract, surfactant 10
A shampoo containing 40% by weight, an oil content of 0 to 5% by weight, a trace amount of fragrance, and the remaining amount of purified water.

(6) In the case of body shampoo 0.1 to 10% by weight of plant extract, surfactant 10
Body shampoo containing 40% by weight, 0 to 5% by weight of oil, trace amount of fragrance, and remaining amount of purified water.

[0029]

EXAMPLES Next, the present invention will be described specifically with reference to examples, but the present invention is not limited to the following examples.

Preparation of Plant Extract Extract A 10-fold amount (w / v) of methanol was added to 5 g of each dried plant shred and extracted for 2 hours. Next, the mixture was filtered and methanol was removed under reduced pressure to obtain each extract as shown in Table 1.

[0031]

[Table 1]

Test Example 1 (5α-reductase activity inhibitory effect) (1) Preparation of 5α-reductase solution Wistar male rats (1) prepared by cervical dislocation
(0 week old) prostate is excised and contains 5 mM Tris-HCl buffer (pH 7.4), 1.5 mM ethylenediaminetetraacetic acid, 1 mM dithiothreitol, 10 mM sodium molybdate and 10% (w / v) glycerol. After homogenizing with a double volume (w / v) solution, 70
The supernatant obtained by centrifugation at 0 × g at 4 ° C. for 10 minutes 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 g for 10 minutes. The peak area of testosterone and its metabolites (DHT, androstanediol) is measured from the extract using a thin-layer chromatography scanner, and the inhibition rate is determined by the following equation (1).

[0033]

(Equation 1)

The results of calculating the 5α-reductase inhibition rate at a concentration of 400 μg / ml for each of the plant extracts obtained in the above Production Examples are shown in Table 2 below. The higher the value, the higher the 5α-reductase inhibitory activity.

[0035]

[Table 2]

Test Example 2 (Effect of Inhibition of Binding between DHT Receptor and DHT) This test was carried out by the method of Takayasu et al.
d Biochemvol 19 p1141-114
6, 1983). (1) Preparation of DHT receptor solution Wistar male rats (10 weeks old) were castrated, and
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 was collected by centrifugation at × g at 4 ° C. for 10 minutes. The supernatant was further centrifuged at 105000 × g at 4 ° C. for 1 hour to obtain a supernatant, and this supernatant was used as a DHT receptor solution. (2) Measurement of DHT receptor binding inhibitory activity 1 nM [ ³ H] DHT (100 Ci / mmol) and 4 nM
A mixture of 00 nM DHT, the receptor solution according to the above item (1), and various concentrations of test samples (250 μl in total volume) was incubated at 4 ° C. for 16 hours, and then 5% (w / v)
Activated carbon and 0.5% (w / v) dextran (MW6
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.

[0037]

(Equation 2)

The results of calculating the DHT receptor binding inhibition rate at a concentration of 400 μg / ml for each plant extract obtained in the above Production Example are shown in Table 3 below. The higher the number,
This shows that the activity of inhibiting DHT receptor binding is high.

[0039]

[Table 3]

As is clear from Tables 2 and 3, Akaku, Angelim da Mata, Sedro, Sedro Loxo,
High anti-male against Koatakuikaua, Kumar, Faeira, Faba Amargoza, Faba Japakhanim, Inga Tete, Jacaranda, Louro Fire, Macacauba, Mogno, Muirapiranga, Pau Amarello, Pau D'Arco, Prakuba, Supira and Supira Amarella. Hormonal effects were noted.

A formulation example containing the product of the present invention having an antiandrogenic effect is shown below. All compounding ratios are% by weight.

Example 1 Lotion Components 1 to 10 were added to Component 12, dissolved, and Component 1 was further dissolved.
1 was added to prepare a lotion. (Ingredients) 1. 1. Glycerin monostearate 1.0% by weight 2. Isopropyl palmitate 3.0 Lanolin 1.0 4. Trimethylglycine 5.0 5. 5. Paraoxybenzoic acid methyl ester 0.1 Stearylcholaminoformylmethylpyridium chloride 1.5 7. Akaku extract 0.58. Angelim da Mata extract 0.59. Sedro extract 0.5 10. Ethanol 10.0 11. Fragrance, pigment trace Purified water balance

Example 2: Emulsions Components 1 to 8 were heated and dissolved at 70 ° C. On the other hand, the component 10 was heated at 70 ° C., and the oil and fat solution (components 1 to 8) was added and emulsified. Then, while cooling, the component 9 was added on the way and cooled to room temperature to prepare an emulsion. (Ingredients) 1. 1. Glyceryl ether 1.5% by weight 2. Polyoxyethylene (20) hydrogenated castor oil 1.5 3. Sorbitan monostearate 1.0 Squalane 10.0 5. Dipropylene glycol 5.0 6. Sedro loxo extract 0.5 7. Core Tacquia extract 0.58. Kumar extract 0.59. Flavor trace amount 10. Purified water balance

Example 3: Ointment Components other than the following 7 were mixed, heated to 70 ° C., gradually cooled, added with component 7 on the way, mixed, and cooled to room temperature to prepare an ointment. (Ingredients) 1. Solid paraffin 10.0% by weight 2. Beeswax 10.0 3. Squalane 10.0 4. Salicylic acid 0.25. Zinc white 0.56. Faeira extract 1.0 7. Fragrance trace amount 8. Vaseline remaining

Example 4 Bath Agent The following components 1 to 6 were mixed to prepare a bath agent. (Ingredients) 1. 1. Sodium sulfate 40.0% by weight Sodium hydrogen carbonate 44.0 3. Faba Amargosa Extract 5.0 4. Faba japacanim extract 5.0 5. Inga Tete Extract 5.0 6. Fragrance, pigment 1.0

Example 5: Hair shampoo A shampoo was prepared by mixing the following components 1 to 8. (Ingredients) 1. 1. Triethanolamine lauryl sulfate 15.0% by weight 2. Lauryl sulfate monoethanolamide 5.0 3. Magnesium stearate 1.5 4. Liquid lanolin 1.05. Jacaranda extract 0.5 6. Louro Fire Extract 0.57. Perfume, pigment 0.28. Purified water balance

Example 6: Hair rinse A rinse was prepared by mixing the following components 1 to 13. (Ingredients) 1. 1. Stearyl dimethyl benzyl ammonium chloride 2.0% by weight 2. Polyoxyethylene cetyl ether 1.2 3. Polyoxyethylene lanolin ether 2.0 Propylene glycol 5.0 5. Citric acid 0.1 6. Sodium citrate 0.17. 7. Butyl paraoxybenzoate 0.05 8. Methyl paraoxybenzoate 0.19. Makakauba extract 0.5 10.10. Mogno extract 0.5 11. Muirapiranga extract 0.5 12. Fragrance 0.2 13. Purified water balance

Example 7: Body shampoo The following components 1 to 12 were mixed to prepare a body shampoo. (Ingredients) 1. Potassium laurate 10.0% by weight 2. Potassium myristate 10.0 3. Coconut oil fatty acid diethanolamide 3.0 4. Lauryl dimethylamine oxide 1.05. Propylene glycol 6.0 6. Purakuba extract 0.57. Jacaranda extract 0.58. Hydroxypropyl methylcellulose 0.5 9. 10. Ethylene glycol distearate 1.0 Tetrasodium edetate tetrahydrate 0.111. Fragrance 1.0 12. Purified water balance

Example 8: Hair tonic The following components 1 to 7 were dissolved in component 8 to prepare a hair tonic. (Ingredients) 1. Ethanol 59.0% by weight 2. Glycerin 5.0 3. Distearyl dimethyl ammonium chloride 1.04. Pau amarero extract 0.55. Pau d'Arco extract 0.5 6. Purakuba extract 0.57. Perfume 0.58. Purified water balance

Example 9: Hair restorer The following components 1 to 5 were mixed to prepare a hair restorer. (Ingredients) 1.90% ethanol 89.5% by weight 2. Faeira extract 3.0 3. Liquid paraffin 5.0 4. Trimethylglycine 2.05. Spice 0.5

Example 10: Antiperspirant (compounding components) 1. Aluminum chlorohydroxide 20.0% by weight Propylene glycol 5.0 3. Ethanol 10.0 4. Fungicide 0.25. Skupira extract 0.5 6. Skupira amarella extract 0.5 7. Perfume 0.2 8. Purified water balance

Example 11: Anti-acne agent After the following components 1 to 7 and 8 to 11 were separately mixed and dissolved, the solution of components 8 to 11 was stirred while the component 1 was added thereto.
Solution 7 was added and emulsified. While cooling this to room temperature, component 12 was added on the way to prepare an acne treatment agent. (Ingredients) 1. Liquid paraffin 5.0% by weight 2. Squalane 14.0 3. Cetostearyl alcohol 6.0 4. Beeswax 1.55. Glycerin monostearate 2.06. POE (20) sorbitan monolaurate 2.0 7. Propylparaben 0.18. Makakauba extract 0.39. Diglycerin 5.0 10. Methyl paraben 0.2 11. Purified water balance 12. Fragrance trace

Example 12: Tablet After the following components 1 to 4 were sufficiently mixed, they were tableted. (Ingredients) Amount per tablet 1. Lactose 180.0mg 2. 2. Purakuba extract 50.0 mg 0.5 mg of stearic acid Potato starch 19.5mg

[0054]

EFFECT OF THE INVENTION The antiandrogen of the present invention is highly safe without hormonal effects such as prostatic hypertrophy or the like, and has high safety, such as red ginger, angelim da mata, cedro, cedro loxo, coataquicaua, Kumar, faeira, faba amargosa, Contains at least one plant extract selected from Faba japacanim, Inga Tete, Jacaranda, Louro Fire, Macacauba, Mogno, Muirapiranga, Pau Amarero, Pau Dalco, Prakuuba, Supira and Supira Amarella as essential ingredients It is useful for preventing sebum secretion, preventing and treating acne, preventing dandruff, itching and hair loss on the scalp.
It can be used in a wide range of cosmetic applications.

Claims (1)

[Claims] (1) Akaku, Angelim da Mata, Sedro,
Sedro Loxo, Koatakuikaua, Kumar, Faeira, Faba Amargoza, Faba Japakhanim, Inga Tete, Jacaranda, Louro Fire, Makakauba, Mogno, Muirapiranga, Pau Amarello, Pau
An antiandrogen comprising as an active ingredient at least one plant extract selected from darco, prauba, skupira and sukupira amarella.