JPH08231347A - Hyaluronidase inhibitor and cosmetic - Google Patents

Abstract

PURPOSE: To obtain a hyaluronidase inhibitor containing an extract of tamarind husk as an active ingredient and having high safety. CONSTITUTION: This hyaluronidase inhibitor is obtained by immersing ground material of tamarind husk into a solvent (e.g. methanol-water) kept to ordinary temperature to boiling point, extracting a hyaluronidase inhibitor, as necessary, carrying out deodorizing and decoloration treatment and purification treatment. Antiallergic action and anti-inflammatory action are given to skin cosmetic by blending 0.001-10wt.%, preferably 0.01-1wt.% of the hyaluronidase inhibitor with the cosmetic. The inhibitor can be added to cosmetic such as skin lotion, cream, milky lotion, shampoo, baby powder, rinse, hair tonic, soap, bathing agent, foundation lotion or lip stick.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a hyaluronidase inhibitor and a cosmetic having an antiallergic action and an antiinflammatory action.

[0002]

BACKGROUND OF THE INVENTION Hyaluronidase is present in various tissues in the living body and is usually in an inactive state. Its physiological significance has not yet been fully elucidated, but several facts have been confirmed, such as activation leading to increased capillary permeability and activation of this enzyme in various inflammations. There is. It is also possible to experimentally create an acute inflammation model using this enzyme. Due to these facts
This enzyme is also called a respiratory enzyme. The enzyme has also been shown to be involved in the development of certain allergies.

Several substances which inhibit the action of hyaluronidase have been identified. Among them, sodium cromoglycate, tranilast and the like are used as antiallergic agents, and indomethacin, aspirin, mefenamic acid and the like are used as antiinflammatory agents. , Respectively, have been proposed.
In addition to these, hyaluronidase inhibitory effects have been confirmed in licorice and sardine.

[0004]

An object of the present invention is to find a highly safe and easy-to-use natural product hyaluronidase inhibitor, and to provide a hyaluronidase inhibitor comprising the hyaluronidase inhibitor.

Another object of the present invention is to provide a cosmetic having anti-inflammatory action and anti-allergic action by containing the above-mentioned natural product hyaluronidase inhibitor.

[0006]

The present invention is based on the novel finding that tamarind husk contains a strong hyaluronidase inhibitor, and a hyaluronidase inhibitor containing the hyaluronidase inhibitor extracted from tamarind husk as an active ingredient. The present invention provides an agent, and a cosmetic comprising a hyaluronidase inhibitor extracted from the tamarind husk.

Tamarind (Tamarindus indica L.) is a legume having a height of 25 m or more. The polysaccharide obtained from the endosperm portion of the seed is called tamarind gum and is widely used as a thickener in food production. The tamarind husk is a portion of a hard seed coat that is discarded when the tamarind gum is produced, and a part of the tamarind husk is conventionally used as a raw material for producing tannin.

Although the main body of the hyaluronidase inhibitor contained in tamarind husk has not been confirmed yet, it is presumed to be a polyphenolic compound. This hyaluronidase inhibitor is obtained by appropriately pulverizing tamarind husk and then lower aliphatic alcohol (eg methanol, ethanol, butanol), lower alkyl ketone (eg acetone, methyl ethyl ketone), lower aliphatic ester (eg ethyl acetate), halogenated It is easily extracted when extracted with hydrocarbons (eg methylene chloride, chloroform), water, etc. The hydrophilic organic solvent can be used as a mixture with up to about 20 times the amount of water. Among these extraction solvents, methanol, ethanol, butanol, acetone, and a mixture thereof with water give an extract having a strong hyaluronidase inhibitory activity in a high yield and are particularly preferable.

It is not necessary to adopt a special method for extraction,
Simply, the active ingredient can be extracted by immersing the pulverized product of tamarind husk in a solvent maintained at room temperature or a temperature near the boiling point.

The extract obtained by distilling off the solvent from the extract can be used as it is as a hyaluronidase inhibitor, but it is subjected to a treatment for deodorization, decolorization, etc. within a range that does not adversely affect the hyaluronidase inhibitory action. May be. Further, it may be subjected to any purification treatment effective for concentrating the hyaluronidase inhibitor before being used as a hyaluronidase inhibitor.

Although the use of the hyaluronidase inhibitor of the present invention is not limited, it is most suitable for use in skin cosmetics, and it is possible to provide a cosmetic having anti-inflammatory and anti-allergic effects. Examples of suitable cosmetics to be added are lotions, creams, emulsions, shampoos, baby powders, rinses, hair tonics, soaps (including body soaps), bath agents, lotions impregnated with non-woven fabrics, foundations, Lip cream, lipstick, etc.

When blended in cosmetics, the preferred blending amount of the hyaluronidase inhibitor of the present invention is about 0.001 to 10% by weight in the case of the unpurified tamarind husk extract having an average hyaluronidase inhibitory activity. , Particularly preferably 0.01 to 1.0% by weight.

The hyaluronidase inhibitor of the present invention is an astringent, rather than being blended alone into a cosmetic base to form a cosmetic.
Sterilizing / antibacterial agents, whitening agents, UV absorbers, moisturizers, cell activators, anti-inflammatory / anti-allergic agents, antioxidants / active oxygen scavengers, etc. When properly combined into a cosmetic, it can be used as a more general cosmetic.
Further, in that case, a synergistic action with other active ingredients used in combination may bring about an excellent use effect more than normally expected.

The following are specific examples of what can be used in combination with the hyaluronidase inhibitor of the present invention as a cosmetic component. Astringent: citric acid or its salts, tartaric acid or its salts, lactic acid or its salts, aluminum chloride, aluminum / potassium sulfate, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum,
Zinc paraphenol sulfonate, Zinc sulfate, Jew extract, Agetsu extract, Hamamellis extract, Gentian ginger extract, Chacatechins, Guy au extract, Odorikosou extract, Hypericum perforatum extract, Rhizoma extract, Cornflower extract, Horsetail extract, Kizuta extract, Cucumber extract, Horse chestnut extract, Salvia extract extract,
Melissa extract etc.

Sterilizing / antibacterial agents: benzoic acid, sodium benzoate, paraoxybenzoic acid ester, distearylmethylammonium chloride, benzethonium chloride, alkyldiaminoethylglycine chloride liquid, chlorhexidine hydrochloride,
Orthophenylphenol, Photosensitizer No. 101, Photosensitizer 2
No. 01, salicylic acid, sodium salicylate, sorbic acid, halocarban, resorcin, parachlorophenol, phenoxyethanol, bisabolol, hinokitiol, menthol, chitosan, chitosan degradation product, diyu extract, kujin extract, nematode extract, loquat extract, hop extract, hop extract, Yucca extract,
Aloe extract, cinnamon extract, zedoary extract, etc.

Whitening agents: ascorbic acid and its derivatives, sulfur, placenta extract, kojic acid and its derivatives,
Glucosamine and its derivatives, Azelaine and its derivatives, Arbutin and its derivatives, Hydroxycinnamic acid and its derivatives, Glutathione, Arnica extract, Ougon extract, Ginseng extract, Sohakuhi extract, Psychoextract, Bow-fu extract, Hamaboufu-extract, Ganoderma lucidum mycelium culture Or its extract, Gymnema extract, linden extract, peach leaf extract, ages extract, kujin extract, juniper extract, Japanese laurel extract,
Yokuinin extract, oyster leaf extract, rhubarb extract, button pipi extract, hamamelis extract, horse chestnut extract, Hypericum perforatum extract, Odorikosou extract, oil-soluble licorice extract (liquorice hydrophobic flavone, glabridin, glabrene, lycochalcone A) and the like.

Ultraviolet absorber: β-isopropylfuranone derivative, urocanic acid, ethyl urocanate, oxybenzone, oxybenzone sulfonic acid, tetrahydroxybenzophenone, dihydroxydimethoxybenzophenone, dihydroxybenzophenone, synoxate, methyl diisopropylcinnamate, octyl methoxycinnamate, paraamino Glyceryl benzoate, amyl paradimethylaminobenzoate, octyl paradimethylbenzoate, paraaminobenzoic acid, ethyl paraaminobenzoate, butylmethoxydibenzoylmethane, titanium oxide, β-carotene, γ-oryzanol, rice bran extract, aloe extract, birch extract , Birch extract, chamomile extract, black-necked extract, hawthorn extract, henna extract, butterfly Extract, horse chestnut extract, ginkgo leaf extract, chamomile extract, hawthorn extract, oil-soluble licorice extract, and the like.

Moisturizers: serine, glycine, threonine,
Alanine, collagen, hydrolyzed collagen, hydronectin, fibronectin, keratin, elastin, royal jelly, chondroitin heparin, glycerophospholipids, glyceroglycolipids, sphingophospholipids, glycosphingolipids, linoleic acid or its esters, eicosapentaenoic acid or its ester , Pectin, Arge colloid, Bifidobacterium fermented product, Lactic acid fermented product, Yeast extract, Reishi mycelium culture or its extract, Wheat germ oil, Avocado oil, Rice germ oil, Jojoba oil, Soybean phospholipid, γ-Oryzanol , Bildoaoi extract, Yokuinin extract, dio extract, tannin extract, Kaiso extract, Kidachialoe extract, burdock extract, horse chestnut extract, mannen wax extract, arnica extract, wheat bran, rice bran extract .

Cell activating agents: riboflavin or a derivative thereof, pyridoxine or a derivative thereof, nicotinic acid or a derivative thereof, pantothenic acid or a derivative thereof, α-tocopherol or a derivative thereof, arnica extract, carrot extract, rapeseed ginger extract, eleuthero extract,
Loofah extract (saponin), shikon extract, birch extract, psyllium extract, button pipi extract, peony extract, sucrose extract, safflower extract, ashitaba extract, loquat leaf extract, Hikiokoshi extract, Yukinoshita extract, yellow musk extract, salvia extract, garlic extract,
Mannen wax extract, etc.

Anti-inflammatory / anti-allergic agents: azulene, allantoin, aminocaproic acid, indomethacin, lysozyme chloride, epsilon aminocaproic acid, oxybenzone, glycyrrhizic acid or its derivative, glycyrrhetinic acid or its derivative, Photosensitizer No. 301, Photosensitizer 401
No., diphenhydramine hydrochloride, tranexamic acid or a derivative thereof, adenosine phosphate, estradiol, estrone, ethinyl estradiol, cortisone, hydrocortisone, prednisone, progesterone, corticosterone, arnica extract, ginkgo biloba extract, sardine essence extract, horse chestnut extract. , Licorice extract, Toki extract, Wormwood extract, Warmoko extract, Gentian extract, Psychoextract, Gypsophila extract, Bowfowl extract, Yarrow extract, Coptis extract, Perilla extract and the like.

Antioxidant / active oxygen scavenger: dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, baicalin, baicalein, superoxide dismutase, catalase, rosemary extract, melissa extract, sardine extract, age extract, loquat leaf extract, Hop extract, hamamelis extract,
Peony extract, sage extract, kina extract, chamomile extract, eucalyptus extract, perilla extract, ginkgo biloba extract, thyme extract, cardamom extract, caraway extract, nutmeg extract, mace extract, laurel extract, clove extract, turmeric extract, willow extract.

In the case of producing a cosmetic containing the hyaluronidase inhibitor of the present invention, there is almost no restriction on the selection of other raw materials for producing cosmetics. Any of the auxiliaries can be used.

Oils and fats: soybean oil, linseed oil, persimmon oil, sesame oil, nuka oil, cottonseed oil, rapeseed oil, safflower oil, corn oil, olive oil, camellia oil, almond oil, castor oil,
Peanut oil, cacao oil, owl, palm oil, palm kernel oil,
Beef tallow, mink oil, egg yolk oil, jojoba oil, evening primrose oil, horse oil

Waxes: carnauba wax, candelilla wax, beeswax, honey beeswax, whale wax, cerax, lanolins

Hydrocarbons: liquid paraffin, petrolatum,
Microcrystalline wax, ceresin, squalane, polyethylene powder

Fatty acids: stearic acid, linoleic acid, lauric acid, myristic acid, palmitic acid, hevenic acid,
Lanolinic acid, oleic acid, undecylenic acid, isostearic acid

Alcohols: lauryl alcohol, cetyl alcohol, stearyl alcohol, lanolin alcohol, hydrogenated lanolin alcohol, oleyl alcohol,
Hexadecyl alcohol, 2-octyldodecanol, glycerin, sorbitol, propylene glycol, 1,3-
Butylene glycol, ethylene glycol and its polymers, glucose, sucrose, cholesterol, phytosterols, cetostearyl alcohol

Esters: decyl oleate, butyl stearate, myristyl myristate, hexyl laurate, isopropyl palmitate, isopropyl myristate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, propylene glycol dioleate, diethyl phthalate, Propylene glycol monostearate, ethylene glycol monostearate, glyceryl monostearate, glyceryl trimyristate, lanolin acetate, cetyl lactate

Surfactant: anionic surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant Fragrance: menthol, carvone, eugenol, anethole, peppermint oil, spearmint oil, Peppermint oil, eucalyptus oil, anise oil

[0030]

The present invention will be described below with reference to examples. The IC ₅₀ value used for showing the hyaluronidase inhibitory activity in Example 1 is a value obtained by the following method, and the smaller this value is, the stronger the hyaluronidase inhibitory activity is.

Assay method for hyaluronidase inhibitory activity: 0.1 ml of hyaluronidase solution (400 units / ml, pH 9.1 borate buffer) and 0.2 ml of sample solution were mixed well, heated to 37 ° C. for 20 minutes, and then activated. Agent solution (0.01% Compound 48
/ 80, 2.5 mM-CaCl ₂ , 0.15M-NaCl) 0.2 ml was added,
The enzyme is activated by heating at 37 ° C for 20 minutes. After adding 0.5 ml of potassium hyaluronate buffer and reacting at 37 ° C. for 40 minutes, 0.2 ml of 0.4N sodium hydroxide was added and the reaction was stopped by cooling with ice. Next, 0.2 ml of 0.8 M boric acid solution (pH 9.1) was added and the mixture was placed in a boiling water bath for 3
After heating for 1 minute, immediately cool with ice for 10 minutes. DMAB reagent (p-dimethylaminobenzaldehyde 10g 10N hydrochloric acid 1
It was dissolved in a mixed solution of 2.5 ml and 87.5 ml of acetic acid, diluted with acetic acid 10 times, and added to 6.0 ml, and kept at 37 ° C. for 20 minutes to develop the color of N-acetylglucosamine liberated by the above-mentioned enzyme reaction, The absorbance at a wavelength of 585 nm is measured.
As a control, the same operation and absorbance measurement are performed when water is added instead of the sample solution.

From the above measurement results, the inhibition rate of hyaluronidase activity is calculated by the following formula. Inhibition rate (%) = [1- (A ₁ −A ₀ ) / (A ₃ −A ₂ )] ×
100 where A _{0 is} the absorbance when the sample solution is added; before the enzymatic reaction is started A ₁ : The absorbance is when the sample solution is added; after the enzymatic reaction is finished A ₂ : Control; before the enzymatic reaction is started A ₃ : Control; the enzyme After completion of the reaction, the concentration of the sample solution is changed stepwise to measure the above inhibition rate, and the sample concentration / IC _{50 at} which the inhibition rate becomes 50% is determined by the interpolation method.

Example 1 100 g of a pulverized product of tamarind husk was extracted with 1000 of extraction solvent.
Soluble components are extracted by immersing them in ml and allowing them to stand at 60 ° C. for 2 hours. Then, the obtained extract is concentrated to dryness under reduced pressure.

Twelve examples of the above extraction procedure were carried out by changing the extraction solvent, and the obtained dried extract was examined for hyaluronidase inhibitory activity. For comparison, the inhibitory activity of a known hyaluronidase inhibitor, cromoglycic acid, was also measured. Table 1 shows the results. The mixing ratio of water and the organic solvent is a volume ratio.

[0035]

[Table 1] Hyaluronidase inhibitory activity of tamarind husk extract Extraction solvent extract yield (wt%) IC ₅₀ (μg / ml) water 9 180 water / ethanol (1/1) 19 110 ethanol 23 120 water / methanol (1 / 4) 23 110 Water / methanol (1/1) 18 110 Water / methanol (4/1) 10 130 Methanol 22 110 Acetone 21 125 n-Butanol 12 230 Ethyl acetate 1.0 580 Methylene chloride 0.4 950 Cromoglic acid (Reference example) 40

Example 2 The following raw materials were uniformly emulsified by a conventional method for cream production to produce a cosmetic cream having antiallergic and antiinflammatory effects. Stearic acid 10 parts by weight Beeswax 3 Cetanol 8 Squalane 10 Glycerin monostearate 3 Polyoxyethylene monolaurate 3 Lanolin derivative 2 Propylene glycol 10 Triethanolamine 1 Perfume 0.5 Tamarind husk extract 0.1 Purified water 49.5 (Tamarind husk extract: methylene chloride extract of Example 1)

Example 3 A lotion having antiallergic and antiinflammatory effects was produced by treating the following raw materials by a conventional method for producing lotion. Citric acid 0.1 part by weight Glycerin 5 Ethanol 15 Fragrance 0.2 Solubilizer 1 Tamarind Husk extract 0.1 Purified water to make 100 parts by weight. (Tamarind Husk Extract: Water / Ethanol of Example 1
(1/1 mixed liquid extract)

Example 4 The following raw materials were treated by a conventional shampoo production method to produce a shampoo having antiallergic and antiinflammatory effects. Lauric acid triethanolamine salt 16 parts by weight Lauric acid diethanolamide 4 Ethylene glycol distearate 2 Ethylene glycol monostearate 2 Butyl parahydroxybenzoate 0.2 Perfume 0.1 Colorant 0.1 Tamarind Husk extract 0.05 Make up to 100 parts by weight with purified water. (Tamarind Husk Extract: Water / Methanol of Example 1
(1/1 mixed liquid extract)

Example 5 The following raw materials were uniformly emulsified by a conventional method for producing an emulsion,
An emulsion having anti-allergic and anti-inflammatory effects was produced. Squalane 5 parts by weight Olive oil 5 Jojoba oil 5 Cetyl alcohol 1.5 Glycerin monostearate 2 Polyoxyethylene (20) cetyl ether 3 Polyoxyethylene (20) sorbitan monooleate 2 Dipropylene glycol 1 Glycerin 2 Perfume 0.1 Paraoxy Methyl benzoate 0.2 Tamarind Husk extract 0.1 Make up to 100 parts by weight with purified water. (Tamarind Husk Extract: Water / Acetone of Example 1
1/1 mixed liquid extract)

[0040]

INDUSTRIAL APPLICABILITY The hyaluronidase inhibitor according to the present invention, which is a highly safe natural product type, is suitable as an additive for imparting antiallergic action and antiinflammatory action to skin cosmetics.

Claims (2)

[Claims] 1. A hyaluronidase inhibitor containing a hyaluronidase inhibitor extracted from tamarind husk as an active ingredient. 2. A cosmetic comprising a hyaluronidase inhibitor extracted from tamarind husk.