JP2006257059A - Androgen receptor binding inhibitor, agent for hair and skin care preparation for dermal use formulated with the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an agent for hair and skin care preparation for dermal use for amelioration of skin condition such as prevention of epilatory, hair restoring/pilatory effect and improvement of skin such as dandruff, pimple and dermatitis. <P>SOLUTION: The invention relates to the agent for hair and the skin care preparation for dermal use formulated with a substance having an androgen receptor binding inhibiting activity as active components comprising one or two or more kinds of solvent extracts selected from a group comprising Adiantum capillus-veneris L., Mucuna pruriens (L.) DC., Murraya koenigii (L.)Spreng., Ocimum sanctum L., Onosma bracteatum, Rosmarinus officinalis, Leonotis nepetifolia (L.)R.Br. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a novel androgen receptor binding inhibitor derived from a plant and an application method thereof.

  Testosterone, a type of male hormone, is reduced by testosterone 5α-reductase, which is a reductase, to dihydrotestosterone (DHT), which has a strong action. The generated DHT binds to a receptor in the hair papilla to form a complex, and a certain protein is synthesized by acting on a specific DNA, which acts on hair follicle epithelial cells, and causes hair growth and hair growth. It is known to cause abnormalities in the cycle (hair cycle), cause hair follicles to shrink, and induce hair loss.

  It is also known that when the production of DHT increases, the sebum secretion ability increases, and seborrheic hair loss and acne (acne vulgaris) develop. Therefore, if DHT can be inhibited from binding to a receptor, it is considered that hair loss prevention, hair growth / hair restoration effect, and acne prevention can be achieved. As an androgen receptor binding inhibitory action, which is an action that DHT inhibits binding to a receptor, oxendron, cyproterone acetate, an extract from the leaves of quince (Japanese Patent Laid-Open No. 2002-241296), majito, extract of cutie Plant extracts such as JP-A-2002-241297 have been reported. However, there is still no product that exhibits a satisfactory effect due to its strength and side effects.

  In order to overcome the above-mentioned problems of the background art, the present invention is a search for a novel substance having excellent androgen receptor binding inhibitory activity and high safety from plant origin. As a result, an extract extracted from a specific plant is obtained. The effect was found and the present invention was reached.

  The androgen receptor binding inhibitors according to the present invention include borage fern (scientific name: Adiantumcapillus-veneris L.), Mucuna pulliers (scientific name: Mucuna pruriens (L.) DC.), Nanyo sansho (scientific name: Murraya koenigii. ) Spreng.), Komibouki (scientific name: Ociumsanctum L.), Onosuma brachatum (scientific name: Onosma bracteaatum), Rosemary (scientific name: Rosmarinus officinalis), Tamazaki-eol. It contains a solvent extract.

  Furthermore, the hair preparation of the present invention is characterized by containing the above-mentioned androgen receptor binding inhibitor.

  The external preparation for skin of the present invention is characterized by containing the above-mentioned androgen receptor binding inhibitor.

  The androgen receptor binding inhibitor of the present invention and hair preparations and skin external preparations containing the same prevent hair loss, hair growth and hair growth effects, and prevent acne, dandruff, dermatitis, etc. The state can be maintained.

物で、和名はマンネンロウ、ヨーロッパ、地中海沿岸地方原産。暖かい乾燥地に生育する。葉からの油は香料や香石鹸の材料としている。中国では全草（迷迭香）が、鎮痛、発汗、健胃の作用があるとされ薬用とされていた。本発明での使用部位は、葉である。
（７）タマザキメハジキ（学名：Ｌｅｏｎｏｔｉｓ ｎｅｐｅｔｉｆｏｌｉａ（Ｌ．）Ｒ．Ｂｒ．，Ｓｔａｃｈｙｓ ｍｅｄｉｔｅｒｒａｎｅａ Ｖｅｌｌ）は、シソ科カエンキセワタ属の植物であり、コルドン・デ・フラーデ（Ｃｏｒｄａｏ ｄｅ ｆｒａｄｅ）の呼び名があり、汎熱帯性の雑草として分布する。民間療法としては、発汗、ぜん息、解熱、強壮、痰とり、子宮出血、排尿困難、傷薬、リューマチに用いられてきた。本発明における使用部位は、全草である。
本発明では、上記植物を単独で或いは二種以上を混合して使用することもできる。Hereinafter, the hair preparation and the skin external preparation according to the present invention will be described in detail. The hair and skin external preparations according to the present invention include borage fern (scientific name: Adiantum capillus-veneris L.), Kamimebouki (scientific name: Ocium sanctum L.), Mukuna pruriens (scientific name: Mucuna pruriens) (L.). Nanyo salamander (Scientific name: Murraya koenigiii (L.) Spreng.), Onosuma bracteatum (Scientific name: Rosmarinus officinalis), Tamazaki efol (L.). It is characterized by containing one or more solvent extracts of the group consisting of. The plant in this invention is shown below.
(1) Holy fern (scientific name: Adiantum capillus-veneris L.) is a plant belonging to the genus Holyidae, and is widely distributed from temperate to tropical regions. In Indian folk remedies, it has been used for palliative, expectorant, diuretic, commuting, tonic and antipyretic. The site used in the present invention is a frond.
(2) Komibouki (scientific name: Ocium santumum L., Ocimum tenuflorum L.) is a plant belonging to the genus Lamiaceae, which is cultivated in India and Southeast Asia, and is used for flavoring dishes. The site used in the present invention is the above-ground part.
(3) Mucuna pruriens (scientific name: Mucuna pruriens (L.) DC.) Is a plant belonging to the family Leguminosae, which is distributed from India to Southeast Asia. In Indian folk remedies, it has been used as an aphrodisiac, cholera treatment, delirium and so on. The site used in the present invention is a seed.
(4) Onosuma bracteatum Wall. Is a plant belonging to the genus Onosuma, which is distributed from West Asia to India. In folk remedies, it is used as a tonic, diuretic, palliative. The sites used in the present invention are leaves and flowers.
(5) Nanyo salamander (scientific name: Murraya koenigii (L.) Spreng.) Is a plant belonging to the genus Ganchiaceae, distributed in India and Sri Lanka, and is commonly found in dry lowlands. It has been used for medicinal purposes such as constipation, stomach ache, diarrhea. The site used in the present invention is a leaf.

The Japanese name is Mannenrou, European and Mediterranean coastal region. Grows in warm dry land. Oil from leaves is used as a material for perfumes and soaps. In China, the whole plant (stinking incense) has been considered medicinal because it has analgesic, sweating, and healthy stomach effects. The site used in the present invention is a leaf.
(7) Tamazaki reptile (scientific name: Leonotis nepetifolia (L.) R. Br., Stachys mediteranea Vell) is a plant belonging to the genus Caenixewata, and is called the tropical name of Cordao de frade. It is distributed as a sex weed. As a folk remedy, it has been used for sweating, asthma, antipyretic, tonic, sputum, uterine bleeding, difficulty urinating, wound medicine, rheumatism. The site used in the present invention is whole grass.
In this invention, the said plant can also be used individually or in mixture of 2 or more types.

  The method for preparing the extract used in the present invention is not particularly limited, and examples thereof include a method of extracting from low temperature to warm using various solvents.

  Specific examples of the extraction solvent include water, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol and other lower monohydric alcohols, glycerin, propylene glycol, dipropylene glycol, and 1,3-butylene. Examples include liquid polyhydric alcohols such as glycol, lower alkyl esters such as ethyl acetate, hydrocarbons such as benzene, hexane, and pentane, ketones such as acetone and methyl ethyl ketone, and ethers such as diethyl ether, tetrahydrofuran, dipropyl ether, and acetonitrile. In addition, one or a mixture of two or more of these can be used.

  The extract used in the present invention may be used as it is, but may be filtered and concentrated as necessary. The extract can also be used after being fractionated and purified by a column chromatography method, a countercurrent distribution method or the like.

  Furthermore, after the above-mentioned product is dried under reduced pressure or freeze-dried, it can be prepared in the form of powder or paste, and can be appropriately formulated and used.

(Production Example 1 of Plant Extract)
3 kg of a 50 vol% ethanol solution is added to 100 g of the plant use site, followed by stirring and extraction at 60 ° C. for 8 hours, followed by cooling and filtration to obtain about 2800 g of Extract A.

(Production Example 2 of Plant Extract)
3 kg of purified water is added to 200 g of the plant use site, and the mixture is extracted by stirring at 80 ° C. for 5 hours. After cooling, it is filtered to obtain about 2600 g of Extract B. Furthermore, 3 kg of 50 vol% ethanol is added to the filtration residue, and the mixture is extracted by stirring at 60 ° C. for 5 hours. After cooling, it is filtered to obtain about 2800 g of Extract C. Further, 3 kg of 95 vol% ethanol is added to the filtration residue, followed by stirring and extraction at 50 ° C. for 5 hours. After cooling, it is filtered to obtain about 2800 g of extract D.

(Production Example 3 of Plant Extract)
The extract B was concentrated to about 200 g under reduced pressure, treated with a column filled with the synthetic adsorbent Diaion HP-20, and washed with water, then 10 vol% ethanol solution eluate, 15 vol% ethanol solution eluate, and 20 vol. An eluate of% ethanol solution is obtained. Each eluate is concentrated under reduced pressure to 50 g, and 50 g of ethanol is added to obtain extracts E, F, and G.

(Production Example 4 of Plant Extract)
4 kg of 30 vol% ethanol is added to 200 g of the plant use site, and the mixture is extracted by stirring at 60 ° C. for 5 hours. After cooling, the mixture is filtered, and the obtained filtrate is concentrated under reduced pressure to 200 g. The concentrated solution was treated with a column packed with octadecylsilylated silica gel for column chromatography, and the fractions eluted with 10-20 vol% ethanol were combined, concentrated under reduced pressure, dried under reduced pressure, and about 15 g of extract H as a powder. Get.

  The extract of the present invention can be used as it is, and can also be blended in hair preparations and skin external preparations, but the blending amount is not particularly specified. Although it varies depending on the type, properties, quality, and expected effect of the product to be blended, it is preferably 0.00001 to 2.5% by weight (hereinafter simply referred to as “%”) in terms of dry solid, especially 0.001 to 1.0% is more preferable. In the case of using an extract, the concentration of the extract is not limited as long as the content of dry solid content as a solute is within the above range.

  When the plant extract of the present invention is used for a hair preparation or an external preparation for skin, in addition to the above-described components, if necessary, it is usually within the range not impairing the effects of the present invention, such as cosmetics, quasi drugs, pharmaceuticals, etc. Components used for external preparations for skin, such as surfactants, oils, moisturizers, thickeners, antioxidants, UV protection agents, alcohols, powder components, colorants, fragrances, aqueous components, water, various skin nutrients Etc. can be appropriately blended as necessary.

  Furthermore, plants having a physiological activity such as sequestering agents, antiseptic antibacterial agents, cell activators, sebum secretion regulators, anti-inflammatory agents, astringents, whitening agents, active oxygen inhibitors, antiallergic agents, antiaging agents, etc. An extract, a microbial extract, an extract fraction, a purified product, and the like can be appropriately blended.

  The androgen receptor binding inhibitor of the present invention and hair preparations and skin external preparations containing the same are not limited to general skin cosmetics, but include pharmaceuticals, quasi-drugs, pharmaceutical cosmetics, etc. To do. The dosage form of the hair preparation and skin external preparation of the present invention may be any of a solubilization system, an emulsification system, a powder dispersion system, a powder system, etc., and the use is also a basic cosmetic such as lotion, emulsion, cream, pack, etc. Makeup cosmetics such as foundations, hair tonics, hair creams, hair liquids, hair lotions, pomades, hair restorers, hair cosmetics such as shampoos and rinses, toiletries such as soaps and body shampoos, bath preparations, etc.

  Next, although an example is given and explained, the present invention is not limited to these examples.

(Test Example 1) Measurement of Androgen Receptor Binding Inhibitory Action Measurement was performed using the A extract of each plant of Production Example 1 as a sample.
A cell line LNCaP cell (TKG0603) showing a proliferation response to androgen was seeded in a 96-well microplate at a cell density of 1.0 × 10 ⁴ cells / well using RPMI-1640 medium containing 2% FBS, 37 ° C., 5% CO ₂ and cultured under. After 24 hours, the medium was changed to RPMI-1640 medium containing 0.5% FBS supplemented with the sample and 10 ⁻⁸ molar DTH, and cultured for 48 hours. Then, it measured by the MTT reduction method.

  In the same manner as described above, in order to examine the effect of the sample alone on LNCap cells, the same culture and measurement were performed by adding only the sample without adding DTH to the RPMI-1640 medium containing 0.5% FBS. Further, as a control, when cultured in a RPMI-1640 medium containing 0.5% FBS without addition of a sample and DTH, and cultured in a RPMI-1640 medium containing 0.5% FBS without adding a sample, only DTH was added. The same measurement was performed for each case. From the measurement results, the binding inhibition rate showing antiandrogenic activity was calculated by the following formula.

Binding inhibition rate (%) = {1− (C−D) / (A−B)} × 100
A: DHT added, no sample added B: DHT, no sample added C: DHT, sample added D: no DHT added, sample added

  Next, the concentration of the sample solution was decreased stepwise to measure the inhibition rate, and the androgen binding inhibition rate (%) at each concentration was determined. The results are shown in Table 1.

(Test results)
As shown in Table 1, it was confirmed that the plant extract of the present invention has a high androgen receptor binding inhibitory action.

  Furthermore, the formulation example of this invention is shown below.

(Example 1) Cream The following components (1) to (10), and separately the following components (11) to (15) are heated and dissolved at 75 ° C. to obtain A solution and B solution, respectively. Liquid B was added to liquid A, emulsified, cooled to 50 ° C. with stirring, and component (16) was added to prepare a cream.
(Ingredient) (wt%)
(1) Jojoba oil 3.0%
(2) Squalane 2.0%
(3) Methyl polysiloxane 0.5%
(4) Stearyl alcohol 0.5%
(5) Cetyl alcohol 0.5%
(6) Tri (capryl / capric acid) glyceryl 12.5%
(7) Glyceryl monostearate 5.0%
(8) 1.5% diglyceryl monostearate
(9) Decaglyceryl monostearate 3.0%
(10) Propyl paraoxybenzoate 0.1%
(11) Xanthan gum 0.1%
(12) Horai fern extract 2.5%
(13) 1,3-butylene glycol 2.5%
(14) Methyl paraoxybenzoate 0.2%
(15) 66.0% purified water
(16) Fragrance 0.1%

(Example 2) Toner lotion The following components (5) to (8) are mixed and dissolved to give solution A, and separately, the following components (1) to (4) and (9) are mixed and dissolved to give solution B, A liquid and B liquid were mixed uniformly and the lotion was adjusted.
(Ingredient) (wt%)
(1) Citric acid 0.1%
(2) Sodium citrate 0.1%
(3) Serine 0.1%
(4) PEG-60 hydrogenated castor oil 0.3%
(5) Perfume 0.02%
(6) 1,3-butylene glycol 3.0%
(7) Methylparaben 0.15%
(8) Dipotassium glycyrrhizinate 0.1%
(9) Glycerin 4.0%
(10) Mucuna pulliers extract 3.0%
(11) 89.13% purified water

(Example 3) Emulsion The following components (1) to (10), and separately (11) to (14) and (16) are heated and dissolved at 75 ° C. to make A liquid and B liquid, respectively. In addition, the mixture was emulsified, cooled to 50 ° C. with stirring, added with component (15), and an emulsion was prepared.
(Ingredient) (wt%)
(1) Jojoba oil 1.0%
(2) Squalane 2.0%
(3) Behenyl alcohol 1.0%
(4) Tri (capryl / capric acid) glyceryl 2.0%
(5) Tetraglycerin condensed silinoleic acid 0.1%
(6) Propylene glycol monooleate 0.5%
(7) Glycerol monostearate 1.0%
(8) Hexaglyceryl monomyristate 1.0%
(9) Decaglyceryl monomyristate 0.5%
(10) Propyl paraoxybenzoate 0.1%
(11) Quince seed extract 5.0%
(12) Onosuma brackatatum extract 3.0%
(13) 1,3-butylene glycol 3.0%
(14) Methyl paraoxybenzoate 0.1%
(15) Fragrance 0.1%
(16) 79.6% purified water

(Example 4) Cleansing Gel The following components (1) to (3), and separately (4) to (6) and (8) were heated and dissolved at 70 ° C. to make A liquid and B liquid, respectively. And stir until uniform. While stirring, the mixture was cooled to 50 ° C. and component (7) was added to prepare a cleansing gel.
(Ingredient) (wt%)
(1) Hexaglyceryl monomyristate 20.0%
(2) Liquid paraffin 59.7%
(3) Paraoxybenzoic acid ester 0.3%
(4) Rosemary extract 5.0%
(5) Concentrated glycerin 5.0%
(6) Sorbitol 5.0%
(7) Fragrance 0.1%
(8) Purified water 4.9%

(Example 5) Packing agent A phase, B phase, and C phase are each uniformly dissolved, solubilized by adding B phase to A phase, and then uniformly dissolved by adding C phase.
(Ingredient) (wt%)
(Phase A) Dipropylene glycol 5.0%
Polyoxyethylene hydrogenated castor oil 5.0%
(Phase B) Olive oil 5.0%
Tocophenol acetate 0.2%
P-Hydroxybenzoate 0.2%
(Phase C) Sodium bisulfite 0.03%
Polyvinyl alcohol 13.0%
Tamakimejiki Extract 1.0%
Ethanol 7.0%
Purified water 63.77%

(Example 6) Hair tonic (1) to (4) and (7) are added to the following component (5) and dissolved by stirring, and then (6) and (8) are added and further stirred.
(Ingredient) (wt%)
(1) Glycerol 3.0%
(2) L-menthol 0.1%
(3) Assembly extract 2.0%
(4) Kamebouki extract 5.0%
(5) Ethanol 53.0%
(6) Fragrance 0.2%
(8) Purified water 36.7%

(Example 7) Shampoo The following components are heated and mixed uniformly.
(Ingredient) (wt%)
(1) N-coconut oil fatty acid glutamic acid triethanol 25.0%
Amine (2) Lauric acid diethanolamide 5.0%
(3) Potassium myristate 5.0%
(4) Ethylene glycol distearate 2.0%
(5) Polyethylene glycol 400 15.0%
(6) Jojoba oil 1.0%
(7) Horai fern extract 3.0%
(8) Chloroxylenol 0.1%
(9) Vitamin E 0.1%
(10) Paraoxybenzoic acid ester 0.2%
(11) Fragrance 0.3%
(12) 43.3% purified water

(Example 8) Bath agent (Ingredient) (wt%)
(1) Dry sodium sulfate 40.0%
(2) Sodium bicarbonate 57.5%
(3) Olive oil 0.2%
(4) Nanyo salamander extract 0.1%
(5) Light anhydrous silicic acid 0.3%
(6) Fragrance 1.7%
(7) Yellow No. 202 (1) 0.2%

(Example 9) Hair restorer (Ingredient) (wt%)
(1) Ethanol 60.0%
(2) Menthol 0.05%
(3) Panthenol 0.1%
(4) Fragrance 0.2%
(5) Mucuna pulliers extract 2.0%
(6) Citric acid 0.02%
(7) Sodium citrate 0.4%
(8) Purified water 37.23%

(Test example 2) Use effect test The effect test at the time of using the skin external preparation of this invention was done. In the use test, 20 men (30 to 60 years old) suffering from thinning hair and hair loss were used as panelists, and the appropriate amount of the hair-restoring agent of Example 9 was applied to 10 people twice a day in the morning and evening for 3 months. In addition, as a control, 10 people used Mukuna-Plurience extract replaced with purified water. The evaluation method was performed according to the following criteria, and the results are shown in Table 2. No one complained of skin abnormalities during use.

"Thin hair"
Effective: Slightly stiff and stiff hair, increased hair volume Slightly effective: Slightly stiff and stiff hair, slightly increased hair volume Invalid or unknown: No change or unknown before use Hair loss "
Effective: Slightly effective with decreased hair loss: Invalid or unknown with decreased hair loss: Unchanged or unknown before use

  As shown in Table 2, it is possible to maintain a state where hair loss is reduced and elasticity is increased in the hair.

Claims (3)

  Horaidaida (scientific name: Adiantum capillus-veneris L.), Mukuna pluriens (scientific name: Mucuna pruriens (L.) DC.), Nanyo salamander (scientific name: Murraya koenigiii (L.) Spleng. L.), Onosuma bracteaatum (scientific name: Onosma bracteatum), Rosemary (scientific name: Rosmarinus officinalis), Takizaki-swordfish (scientific name: Leonotis nepetifolia (L.) R. Br. An androgen receptor binding inhibitor comprising an extract as an active ingredient.   An androgen receptor binding inhibitor according to claim 1 and a hair preparation comprising the same.   The androgen receptor binding inhibitor according to claim 1 and an external preparation for skin containing the same.