JP2005023021A - Elastase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an elastase inhibitor comprising a solvent extract of Ganoderma lucidum. <P>SOLUTION: The elastase inhibitor comprises the solvent extract of Ganoderma lucidum( belonging to Ganodermataceae ). The solvent extract of Ganoderma lucidum exhibits excellent elastase inhibitory effect. Cosmetics, quasi-drugs, pharmaceuticals or foods each containing the solvent extract of Ganoderma lucidum have human aging preventive effects. In this inhibitor, Ganoderma lucidum is e.g. kuro-reishi, reishi(akashi), shishi, each used in a crude drug: bracket fungus of the genus Fomes. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【００４４】
実験例２ モニターテスト
実施例１〜３及び比較例１で得られる各クリームを用いて、各々女性３０人（３０〜４５歳）を対象に１ヶ月間の使用試験を行った。使用後、肌のシワ、タルミの改善効果をアンケートにより測定した。
【００４５】
これらの試験結果を表２に示した。その結果、実施例１〜３のクリームは優れたシワ、タルミの改善効果を示した。なお、試験期間中皮膚トラブルは一人もなく、安全性においても問題なかった。また、処方成分の劣化についても問題なかった。
【００４６】
【表２】

【００４７】
実施例４〜１１についても使用試験を行ったところ、安全で優れた肌のシワ、タルミの改善効果を示した。また、実施例１２〜１６については１ヶ月間内服させた結果、老化防止効果が認められた。
【００４８】
【発明の効果】
以上のことから、本発明のマンネンタケの溶媒抽出物は優れたエラスターゼ阻害効果を示し、また、マンネンタケの溶媒抽出物を含有する化粧品、医薬部外品、医薬品または食品は老化防止効果を示した。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an elastase inhibitor containing a solvent extract of garlic mushroom as an active ingredient, and further, it is possible to prevent cellular senescence by internal or external use.
[0002]
[Prior art]
The skin is composed of epidermis, dermis, and subcutaneous tissue. Above all, the dermis is extremely important for maintaining the structure of the skin, and the skin is maintained by the dermal connective tissue formed from fibers such as elastin and collagen. It is believed that this connective tissue loses its contractile force and further loses its elasticity, resulting in the occurrence of skin talmi and wrinkles.
[0003]
As a characteristic of the skin exposed to ultraviolet rays, it has been clarified that the network structure disappears due to the degradation of elastic fiber elastin which is an extracellular matrix of the dermis. In addition, excessive degradation of elastin is considered to cause arteriosclerosis, emphysema, rheumatoid arthritis, and the like.
[0004]
One of the causes of elastin degradation is considered to be degradation by elastase. By inhibiting the degradation, it is considered that skin tarmi, wrinkles, arteriosclerosis, etc. can be prevented or improved. In recent years, many skin external preparations and internal preparations that prevent or improve the skin talmi, wrinkles, arteriosclerosis and the like have been known, and retinoic acid, α-hydroxy acid, retinol and the like (for example, Patent Document 1 and Non-Patent Document 1) have reported isoflavonoids, elderberry extract (see, for example, Patent Document 2 and Patent Document 3) and the like as active ingredients of internal preparations. However, some of these active ingredients have problems with skin irritation and stability, and some have insufficient effects. Moreover, although the cosmetics which mix | blended the solvent extract of Mannentake are described in patent document 4, it was not reported that the solvent extract of Mannentake has an elastase inhibitory effect.
[0005]
[Patent Document 1]
JP-A-5-112422 [Patent Document 2]
Special Table 2002-511860 [Patent Document 3]
JP-A-11-147832 [Patent Document 4]
JP 58-113118 [Non-patent Document 1]
Journal of the Japan Cosmetic Science Society, 16 (3), 172-174, 1992
[0006]
From the above, a safe and stable skin external preparation and internal preparation that are effective in preventing or improving aging of cells such as skin talmi and wrinkles and arteriosclerosis are desired.
[0007]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide an elastase inhibitor having an effect of preventing or improving aging such as skin talmi, wrinkles and arteriosclerosis.
[0008]
[Means for Solving the Problems]
As a result of intensive studies aimed at solving the above problems, the present inventors have found that the solvent extract of Mannentake has an excellent elastase inhibitory effect. In addition, among Ganoderma mushrooms, the solvent extract of black ganoderma is excellent in this effect. Furthermore, the elastase can be synergistically combined with the solvent extract of black ganoderma biloba and ganoderma (Akashiba). The present invention has been completed.
[0009]
That is, the present invention is an elastase inhibitor characterized by using a solvent extract of Mannentake as an active ingredient.
[0010]
Hereinafter, the configuration of the present invention will be described in detail. The mannambose used in the present invention is a basidiomycete used in the herbal medicine “Ganoderma”, belongs to the family Ganodermaaceae, Ganoderma, Ganoderma (red turf), black ganoderma (black turf), purple turf Etc. are included. According to the literature [Acta Microbiological Sinica 19 (3), 265-279, 1979], the scientific name is Ganoderma lucidum (scientific name: Ganoderma atrum), Shishiba (scientific name: Ganoderma). Although it is classified, it is not limited to it. As the bamboo shoot used in the present invention, those widely distributed in China and the Japanese market can be used.
Also, among the mushrooms, black ganoderma is preferred, and it is most preferred to use a combination of black ganoderma and ganoderma (red turf).
[0011]
Examples of the solvent to be extracted include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol). , Glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether) Etc.). Water, lower alcohol and liquid polyhydric alcohol are preferable, and water, ethanol, 1,3-butylene glycol and propylene glycol are particularly preferable. These solvents may be used alone or in combination of two or more.
[0012]
The solvent extract of Mannentake may be used as it is, or may be used after treatment such as concentration, dilution, filtration, decolorization or deodorization with activated carbon or the like, if necessary. Furthermore, the extracted solution may be subjected to treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.
[0013]
In the elastase inhibitor of the present invention, the above extract may be used as it is, and it is a component used in cosmetics, quasi-drugs, pharmaceuticals, foods, etc. within a range not impairing the effect of the extract. Fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments In addition, components such as an antioxidant, a whitening agent, a chelating agent, an excipient, a film agent, a sweetener, and a sour agent can be blended.
[0014]
The elastase inhibitor of the present invention can be blended in cosmetics, quasi drugs, pharmaceuticals or foods for the purpose of preventing or improving aging, and the blending amount is 0.0001% by weight or more, preferably 0.001 to 10% by weight. If it is less than 0.0001% by weight, the effect of the present invention is not sufficiently exerted, and even if it is added in an amount of 10% by weight or more, the effect is hardly observed and it is uneconomical. Moreover, each compounding ratio in the case of using a combination of black ganoderma and ganoderma (red turf) is 50: 1 to 1:50 by weight ratio, preferably 10: 1 to 1:10. When the blending amount of one is less than 2% by weight of the other, the combined effect is hardly observed.
[0015]
Examples of the dosage form of the present invention include lotions, creams, emulsions, gels, aerosols, packs, cleaning agents, bath preparations, foundations, powders, lipsticks, ointments, poultices, pastes, plasters, essences, Powders, pills, tablets, injections, suppositories, emulsions, capsules, granules, liquids (including tinctures, fluid extracts, spirits, suspensions, limonades, etc.), tablet confectionery, beverages, etc. Can be mentioned.
[0016]
【Example】
Next, in order to explain the present invention in detail, examples are given, but the present invention is not limited to these examples. The part of the blending amount shown in the examples indicates part by weight.
[0017]
Production Example 1 Black Ganoderma Hot Water Extract 400 g of purified water was added to 20 g of the dried product of Kuro Ganoderma, extracted at 95-100 ° C. for 2 hours, filtered, and the filtrate was concentrated, lyophilized and blackened. 1.4 g of Ganoderma hot water extract was obtained.
[0018]
Production Example 2 Black Ganoderma Ethanol Extract 100 g of dried ganoderma turf was added with 900 mL of ethanol, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness to obtain a black ganoderma ethanol extract. 1.5g was obtained.
[0019]
Production Example 3 1,3-butyleneglycol aqueous solution extract of black ganoderma After adding 1.0 kg of purified water and 1.0 kg of 1,3-butyleneglycol to 100 g of the dried product of black ganoderma and extracting it at room temperature for 7 days, Filtration was performed to obtain 1.9 kg of a 1,3-butylene glycol aqueous solution extract of black ganoderma.
[0020]
Production Example 4 Hot Water Extract of Ganoderma (Akashiba) 400 mL of purified water was added to 20 g of dried ganoderma (Akashiba), extracted at 95-100 ° C. for 2 hours, filtered, and the filtrate was concentrated and frozen. After drying, 2.0 g of hot water extract of Reishi (Akashiba) was obtained.
[0021]
Production Example 5 Ethanol Extract of Ganoderma (Akashiba) 900 mL of ethanol was added to 100 g of dried ganoderma (Akashiba), extracted for 7 days at room temperature, filtered, and the filtrate was concentrated to dryness. 2.5 g of ethanol extract of Akashiba) was obtained.
[0022]
Production Example 6 1,3-butyleneglycol aqueous solution extract of Ganoderma (Akashiba) 1.0 kg of purified water and 1.0 kg of 1,3-butyleneglycol are added to 100 g of dried ganoderma (Akashiba), and it is kept at room temperature for 7 days. After extraction, the mixture was filtered to obtain 1.9 kg of a 1,3-butylene glycol aqueous solution extract of Reishi (Akashiba).
[0023]
Example 1 Cream 1
Formulation Formulation 1. Black Reishi hot water extract (Production Example 1) 0.5 part2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7. Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.1
11. 1,3-butylene glycol 8.5
12 Ethyl paraoxybenzoate 0.05
13. Methyl paraoxybenzoate 0.2
14 Purified water 67.65
[Manufacturing method] Components 2 to 9 are heated and dissolved and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 11 to 14 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.
[0024]
Example 2 Cream 2
In Example 1, cream 2 was obtained by replacing the hot water extract of black ganoderma with the hot water extract of Ganoderma (Akashiba) (Production Example 4).
[0025]
Example 3 Cream 3
In Example 1, 0.25 parts of Kuro Ganoderma hot water extract (Production Example 1) and 0.25 part of Ganoderma (Akashiba) hot water extract (Production Example 4) 0.25 What was replaced by the part was Cream 3.
[0026]
Comparative Example 1 A conventional cream obtained by replacing the hot water extract of black ganoderma with purified water in Example 1 of the conventional cream was used.
[0027]
Example 4 Lotion Formulation Formulation 1. 10.0 parts of 1,3-butylene glycol aqueous solution extract of Kuro Reishi (Production Example 3)
2. 1,3-butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7. Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Fragrance 0.1
11. Purified water 74.57
[Production method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved, and both are mixed and filtered to obtain a product.
[0028]
Example 5 Latex 1
Formulation Formulation 1. Black Reishi lawn ethanol extract (Production Example 2) 0.5 part2. Squalane 5.0
3. Olive oil 5.0
4). Jojoba oil 5.0
5. Cetanol 1.5
6). Glycerol monostearate 2.0
7. Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Polyoxyethylene sorbitan monooleate 2.0
(20 EO)
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12 Methyl paraoxybenzoate 0.2
13. Purified water 72.7
[Manufacturing method] Components 1 to 8 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 10 to 13 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 9 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.
[0029]
Example 6 Latex 2
In Example 5, the black extract of Kuro Reishi was replaced with 0.25 parts of Kuro Reishi ethanol extract (Production Example 2) and 0.25 parts of Reishi (Akashiba) ethanol extract (Production Example 5). This was designated as Emulsion 2.
[0030]
Example 7 Gel formulation formulation 0.1 part of 1,3-butylene glycol aqueous extract of black reishi (Production Example 3)
2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Fragrance 0.1
6). 1,3-butylene glycol 5.0
7. Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. Purified water 84.1
[Manufacturing method] Components 2 to 5 and components 1 and 6 to 11 are uniformly dissolved and mixed to obtain a product.
[0031]
Example 8 Pack formulation 0.1 part of 1,3-butylene glycol aqueous extract of black reishi (Production Example 3)
2. 1,3-butylene glycol aqueous solution extract of Reishi (Akashiba) 0.1
(Production Example 6)
3. Polyvinyl alcohol 12.0
4). Ethanol 5.0
5. 1,3-butylene glycol 8.0
6). Methyl paraoxybenzoate 0.2
7. Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
8). Citric acid 0.1
9. Sodium citrate 0.3
10. Fragrance 0.1
11. Purified water 73.6
[Production Method] Components 1 to 11 are uniformly dissolved to obtain a product.
[0032]
Example 9 Foundation formula 1.0 part of 1,3-butylene glycol aqueous extract of black reishi (Production Example 3)
2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate 1.0
(20 EO)
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7. Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Butyl paraoxybenzoate 0.1
10. Sodium carboxymethylcellulose 0.1
11. Bentonite 0.5
12 Propylene glycol 4.0
13. Triethanolamine 1.1
14 Methyl paraoxybenzoate 0.2
15. Titanium dioxide 8.0
16. Talc 4.0
17. Bengala 1.0
18. Yellow iron oxide 2.0
19. Fragrance 0.1
20. Purified water 60.0
[Manufacturing method] Components 2 to 9 are heated and dissolved and kept at 80 ° C to obtain an oil phase. Swell component 10 well with component 20, then add components 1 and 11-14 and mix uniformly. To this, components 15 to 18 pulverized and mixed with a pulverizer are added, and the mixture is stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The oily phase is added to the aqueous phase with stirring, cooled, and component 19 is added at 45 ° C, and cooled to 30 ° C with stirring to give a product.
[0033]
Example 10 Bath preparation formulation Black Reishi hot water extract (Production Example 1) 1.0 part2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) 0.1
4). Fragrance 0.1
5. Anhydrous sodium sulfate 48.8
[Production method] Components 1 to 5 are uniformly mixed to obtain a product.
[0034]
Example 11 Ointment Formulation Formulation 1. Black Reishi hot water extract (Production Example 1) 1.0 part2. Polyoxyethylene cetyl ether (30E.O.) 2.0
3. Glycerol monostearate 10.0
4). Liquid paraffin 5.0
5. Cetanol 6.0
6). Methyl paraoxybenzoate 0.1
7. Propylene glycol 10.0
8). Purified water 65.9
[Manufacturing method] Components 2 to 5 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 6 to 8 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled to 30 ° C. with stirring to obtain a product.
[0035]
Example 12 Powder 1
Formulation Formulation 1. Black Reishi hot water extract (Production Example 1) 1.0 part2. Reishi (Akashiba) hot water extract (Production Example 4) 1.0
3. Dried corn starch 38.0
4). Microcrystalline cellulose 60.0
[Production method] Components 1 to 4 are mixed to form a powder.
[0036]
Example 13 Powder 2
In Example 12, the hot water extract of black ganoderma was used as the ethanol extract of black ganoderma (Production Example 2), and the hot water extract of ganoderma (Akashiba) was used as the ethanol extract of ganoderma (Akashiba). The powder 2 was replaced with (Production Example 5).
[0037]
Example 14 Tablet formulation Ethanol extract of black reishi (Production Example 2) 2.5 parts Reishi (Akashiba) ethanol extract (Production Example 5) 2.5
3. Dried corn starch 25.0
4). Carboxymethylcellulose calcium 20.0
5. Microcrystalline cellulose 40.0
6). Polyvinylpyrrolidone 7.0
7. Talc 3.0
[Production method] Components 1 to 5 are mixed, and then an aqueous solution of component 6 is added as a binder to form granules. Ingredient 7 is added to the molded granules and compressed. One tablet is 0.52 g.
[0038]
Example 15 Tablet confection formulation Black Reishi hot water extract (Production Example 1) 1.0 part2. Reishi (Akashiba) hot water extract (Production Example 4) 1.0
3. Dried corn starch 49.8
4). Erythritol 40.0
5. Citric acid 5.0
6). Sucrose fatty acid ester 3.0
7. Fragrance 0.1
8). Purified water 0.1
[Production Method] Components 1 to 5 and 8 are mixed and granulated. Add ingredients 6 and 7 to the molded granules and compress. One tablet is 1.0 g.
[0039]
Example 16 Beverage Formulation Black Reishi hot water extract (Production Example 1) 2.5 parts Reishi (Akashiba) hot water extract (Production Example 4) 2.5
3. Stevia 0.05
4). Malic acid 5.0
5. Fragrance 0.1
6). Purified water 89.85
[Production Method] Components 3 and 4 are dissolved in a small amount of water. Components 1, 2, 5 and 6 are then added and mixed.
[0040]
Next, experimental examples will be given to explain the effects of the present invention in detail.
[0041]
Experimental Example 1 Elastase Inhibitory Effect The elastase inhibitory effect was determined using the black ganoderma extract of Production Examples 1 and 2 and the ganoderma (Akashiba) extract of Production Examples 4 and 5. 50 μL of an enzyme solution [prepared to 20 ppm by adding 0.2 M Tris-HCl buffer (pH 8.0) to elastase type III (manufactured by Sigma)] to 50 μL of the sample ethanol solution was added. Substrate (1 mM N-Succinyl-Ala-Ala-Ala-p-Nitroamide aqueous solution) 100 μL was added and reacted at 25 ° C. for 50 minutes, and then the absorbance at 415 nm was measured. Moreover, the inhibitory effect of each sample was computed by the inhibition rate calculated | required from the following formula. For the control, purified water was used instead of the sample, and purified water was used instead of elastase as a blank.
Inhibition rate (%) = [1- (C−D) / (A−B)] × 100
A: Absorbance at 415 nm of control (OD 415)
B: O. D. 415
C: Sample O.D. D. 415
D: Sample blank O.D. D. 415
[0042]
These results are shown in Table 1. As a result, the black ganoderma extract of Production Examples 1 and 2 and the ganoderma (Akashiba) extract of Production Examples 4 and 5 showed excellent elastase inhibitory effects. Furthermore, a 1: 1 mixture of black reishi and reishi (Akashiba) extracts showed a higher inhibitory effect than their respective effects, indicating their synergistic effect.
[0043]
[Table 1]

[0044]
Experimental Example 2 Using each cream obtained in Monitor Test Examples 1 to 3 and Comparative Example 1, a use test for one month was conducted for 30 women (30 to 45 years old). After use, the effect of improving skin wrinkles and tarmi was measured by questionnaire.
[0045]
The test results are shown in Table 2. As a result, the creams of Examples 1 to 3 showed excellent wrinkle and tarmi improving effects. During the test period, there was no skin problem and there was no problem with safety. There was also no problem with the deterioration of the prescription ingredients.
[0046]
[Table 2]

[0047]
Examples 4 to 11 were also tested for use, and showed a safe and excellent skin wrinkle and tarmi improving effect. Moreover, about Examples 12-16, as a result of taking it for one month, the anti-aging effect was recognized.
[0048]
【The invention's effect】
From the above, the solvent extract of Mannentake of the present invention showed an excellent elastase inhibitory effect, and cosmetics, quasi drugs, pharmaceuticals or foods containing the solvent extract of Mannentake showed an anti-aging effect.

Claims (4)

An elastase inhibitor comprising a solvent extract of Mannentake. The elastase inhibitor according to claim 1, wherein the mannambose is black ganoderma. An elastase inhibitor comprising a solvent extract of black reishi and reishi (Akashiba). A cosmetic, quasi-drug, pharmaceutical or food containing the elastase inhibitor according to any one of claims 1 to 3 for the purpose of preventing aging.