JPH06329544A - Hyaluronidase inhibitor - Google Patents

Abstract

(57) [Summary] (Corrected) [Structure] Taranoki, Myrica nagi, Par
A hyaluronidase inhibitor comprising as an active ingredient at least one plant or herbal medicine extract selected from the group consisting of melia perlata and areca nut. Anti-inflammatory or anti-allergic agents, cosmetics and foods containing the hyaluronidase inhibitor. [Effect] By ingesting the food containing the hyaluronidase inhibitor of the present invention on a daily basis, inflammation, hay fever, cough, etc. can be prevented or ameliorated. Similarly, the use of cosmetics containing the hyaluronidase inhibitor can improve itchiness and the like of the skin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is directed to the Ararai (Arali)
a elata), Myrica nagi, Parm
elia perlata and areca (Arec
ae Semen) relates to a hyaluronidase inhibitor containing at least one plant or crude drug extract selected from the group consisting of ae Semen) as an active ingredient, and more specifically, an anti-inflammatory or anti-allergic agent containing the hyaluronidase inhibitor as an active ingredient, and The present invention relates to foods and cosmetics containing a hyaluronidase inhibitor.

[0002]

It is known that histamine is involved in the development of inflammation and allergies. When histamine is released from mast cells, it is highly likely that it is mediated by hyaluronidase. This enzyme also plays a role in destroying the connective tissue matrix and promoting the infiltration of inflammatory cells into tissues and the permeability of blood vessels.Therefore, administration of an inhibitor of hyaluronidase causes inflammation and allergic reactions. Suppressed. In fact, anti-allergic ingredients such as sodium cromoglycate and tranilast are known to be inhibitors of hyaluronidase.

Although much research has been conducted on anti-inflammatory and anti-allergic properties related to pharmaceutical ingredients, as a food material, Rakan fruit extract and the like are used only based on the tradition. Various kinds of cosmetic raw materials having anti-inflammatory or anti-allergic activity have been searched,
The safe and promising ones have not been obtained yet.

[0004]

[Problems to be Solved by the Invention] For the 21st century, there is a growing demand for prevention rather than treatment of diseases. For example,
Inflammation and allergies may be considered to be an overreaction of the human body's resistance, but some precautionary measures are required when suffering from the onset of illness. It is desirable to take this measure for foods and cosmetics that are ingested or used on a daily basis, but no useful food material or cosmetic raw material having anti-inflammatory or anti-allergic activity has been obtained. The provision of such materials and raw materials remains an issue.

In addition, maintaining the hyaluronic acid content of the living body,
The need to increase is not just a skin issue. The water retention structure by hyaluronic acid also plays an important role in the aorta and joint fluid. As aging is accompanied by a decrease in the hyaluronic acid content of the human body, it is expected that the need to maintain the water content retained by hyaluronic acid, and thus the flexibility, of the skin and blood vessels, etc., is expected to increase in order to achieve an aging society. It At present, attention is paid only to hyaluronic acid which is externally used as a moisturizer for cosmetics, and there are almost no attempts to maintain the hyaluronic acid content in the human body and thus the water content, which remains an important issue.

[0006]

[Means for Solving the Problems] As a result of an intensive search to find a natural product which inhibits hyaluronidase, which is a hydrolase of hyaluronic acid, the present inventors have found that it was found in solvent extracts of four kinds of plants or herbal medicines. The inventors found the strong inhibitory activity and completed the present invention.

[0007] That is, the first object of the present invention is, Arara elata, Myrica nag
It is intended to provide a hyaluronidase inhibitor containing, as an active ingredient, an extract of at least one plant or herbal medicine selected from the group consisting of i, Parmelia perlata and areca (Arecae Semen). Another object of the present invention is to provide an anti-inflammatory or antiallergic agent containing the hyaluronidase inhibitor as an active ingredient, and cosmetics and foods containing the hyaluronidase inhibitor.

The four kinds of plants or herbal medicines used in the present invention have been used for a long time, but none of them have known anti-inflammatory and anti-allergic effects. Of these, Aralia elata belongs to the family Araliaceae, and its bark (mainly root bark) is Ara-liae.
Cortex is called Souboku, and both are said to be effective for diabetes, kidney disease, gastrointestinal disease, etc. in the private sector.
Myrica nagi belongs to the bayberry family, Kata
It is called by the name of crude drug called pal. Parmeli
a perlata belongs to the family Asteraceae and is a crude drug name.
Saileya and areca are the seeds of areca (Ace catechu L.), which is a palm plant.

The solvent used for extraction may be any solvent selected from the group consisting of water, alcohols such as methanol or ethanol, or ketones such as acetone, or an arbitrary mixed solvent of two or more solvents. Among these solvents, water, ethanol, or a mixed solvent thereof is preferably used from the viewpoint of safety, considering that the extract will be finally mixed in foods and the like.

The ratio of the plant or herbal medicine to the solvent at the time of extraction is not particularly limited.
The solvent is preferably 2 to 1000 times by weight, particularly 5 to 100 times by weight in terms of extraction operation and efficiency. Extraction temperature is room temperature-
It is convenient to set the boiling point of the solvent under normal pressure, and the extraction time varies depending on the extraction temperature and the like, but it is preferably in the range of 2 hours to 2 weeks.

The hyaluronidase inhibitor of the present invention comprising the above-mentioned plant or crude drug thus obtained may be in any state such as the extract as it is or the dried product obtained by removing the solvent from the extract. However, it is preferable to make it a dried product in terms of storability and easy handling. Further, the hyaluronidase inhibitor may be a mixture of two or more kinds of plants or herbal extracts.

The anti-inflammatory agent or anti-allergic agent of the present invention can be prepared by formulating the above-mentioned hyaluronidase inhibitor as it is or with a known pharmaceutical carrier. The pharmaceutical carrier that can be used for preparation is not particularly limited, and those commonly used can be used, examples of which include starch, lactose,
Solid carriers such as sucrose, mannitol, carboxymethylcellulose, corn starch, and inorganic salts; distilled water, physiological saline, aqueous glucose solutions, alcohols such as ethanol, liquid carriers such as propylene glycol, polyethylene glycol; various animal and vegetable oils, white vaseline, Examples include oily carriers such as paraffin and wax. Examples of dosage forms include oral agents such as tablets, granules, powders and syrups, and parenteral agents such as suppositories and external preparations.

Further, the food and cosmetics of the present invention can be produced by blending the above-mentioned hyaluronidase inhibitor with appropriate components usually used depending on the purpose. For example, when producing the food of the present invention, in addition to the hyaluronidase inhibitor, glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, corn syrup, lactose, citric acid, tartaric acid,
Malic acid, succinic acid, lactic acid, L-ascorbic acid, dl
-Α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan,
Casein, gelatin, pectin, agar, vitamin Bs,
Nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, preservatives, and the like are appropriately mixed with those commonly used as food ingredients, candy,
Chewing gum, milk, yogurt, whey beverage, lactic acid bacteria beverage, juice, beverage, ice cream, pudding,
Water cans and the like can be manufactured.

Further, when producing the cosmetics of the present invention, in addition to the hyaluronidase inhibitor, oils and fats such as vegetable oils, waxes such as lanolin and beeswax, hydrocarbons, fatty acids, higher alcohols and esters. , Various surfactants, pigments, fragrances, vitamins, plant / animal extract components, UV absorbers, antioxidants, antiseptic / bactericidal agents, etc. And other anti-inflammatory / anti-allergic cosmetic ingredients such as licorice extract component (especially glycyrrhizic acid),
The effect can also be enhanced by using it together with diphenhydramine hydrochloride, azulene, dl-α-tocopherol and its derivative, vitamins B2 and B6 and the like.

In producing the cosmetic of the present invention,
By using the hyaluronidase inhibitor in combination with hyaluronic acid, the moisturizing effect can be further enhanced. The hyaluronidase inhibitor alone has an indirect moisturizing / skinning effect by blocking the decomposition of hyaluronic acid in the skin, but other moisturizing / skinning cosmetic ingredients such as elastin, collagen, lecithin, squalene, plastic Center liquid (placenta extract), glycerins, glycols, fermentation metabolites, lactic acid bacteria culture fluid, vitamins A and C, sodium chondroitin sulfate, 2-pyrrolidone-
The effect can be further enhanced by using it together with a plant polysaccharide such as sodium 5-carboxylate (PCA-Na) and Bacmondum mucilage polysaccharide.

The hyaluronidase inhibitor is a lotion, cosmetic cream, emulsion, foundation, lipstick, hair styling agent,
In addition to hair tonics and hair restorers, it can be added to toothpaste, mouthwash, shampoo, rinse, bath salts and the like.

The plant or crude drug of the present invention has been used for a long time in Asia and the like, and the extract thereof used in the present invention has no problem in terms of safety. However, the content of the legume extract in the medicine of the present invention is 0.00, in terms of dry weight, in terms of effects and fragrance and color tone when added.
It is desirable to set the concentration range of 01 to 5.0%.

[0018]

ACTION AND EFFECTS OF THE INVENTION
ia elata), Myrica nagi, Par
Melia perlata and areca (Are
The hyaluronidase inhibitor consisting of an extract of cae Semen) showed an activity equal to or higher than that of sodium cromoglycate, an active ingredient of antiallergic agents.
Therefore, the hyaluronidase inhibitor of the present invention is useful as a drug having an anti-inflammatory action and an anti-allergic action. In addition, by ingesting foods containing these hyaluronidase inhibitors on a daily basis, it is possible to prevent / ameliorate inflammation and sore throat, hay fever, cough and the like associated with the cold. Similarly, the use of cosmetics containing the hyaluronidase inhibitor can improve itchiness and the like of the skin.

The hyaluronidase inhibitor of the present invention is
As a powerful inhibitor of hyaluronic acid degradation, it suppresses the decrease of hyaluronic acid content in the skin, arterial wall, joint cavity, etc. Although this is an indirect action, it enhances the moisture retention and flexibility of the skin, prevents arteriosclerosis associated with aging, and contributes to the improvement of arthritis.

[0020]

EXAMPLES The present invention will be described in more detail with reference to the examples of the method for producing a hyaluronidase inhibitor of the present invention, the hyaluronidase inhibition test and the production of anti-inflammatory agents, antiallergic agents, foods and cosmetics. Are not limited to these examples. Example 1: Production of Souboku (Taranoki) extract 100 g of Souboku was soaked in 1000 ml of 50% by volume ethanol at room temperature for 7 days, and the supernatant was filtered and the extract obtained was concentrated to dryness under reduced pressure. , 8.7 g of the extract was obtained.

Example 2: Myrica nagi extraction
Manufacture of Myrica nagi (100 g) was immersed in 1000 ml of 50% by volume ethanol at room temperature for 7 days, the supernatant was filtered, and the extract obtained was concentrated to dryness under reduced pressure to obtain extract 1
5.6 g was obtained.

Example 3: Parmelia perl
Preparation of ata extract 100 g of Parmelia perlata
The extract obtained by immersing in 00 ml of 50% by volume ethanol at room temperature for 7 days and filtering the supernatant was concentrated to dryness under reduced pressure to obtain 6.0 g of extract.

Example 4 Preparation of Areca Nut Extract 100 mg of areca nut were soaked in 1000 ml of 50% by volume ethanol at room temperature for 7 days, and the supernatant liquid was filtered to obtain an extract solution which was concentrated to dryness under reduced pressure and extracted. 31.7 g of the product was obtained.

Example 5: Hyaluronidase inhibitory activity
The hyaluronidase inhibitory activity of the extracts obtained in Assay Examples 1 to 4 was measured by the following method. The results are shown in Table 1.

(Measurement method) Hyaluronidase (Sigma, Type IV) derived from beef testis was used to measure mainly the inhibitory effect of compound 48/80 on the activation stage of the inactive enzyme. The enzymatic activity was measured by colorimetrically quantifying an increase in the reducing power of a tetrasaccharide having N-acetylhexosamine, which is produced by hydrolysis of hyaluronic acid, as a reducing end by A585 (Yumee Maeda et al. 31: 233-237, 1990). That is, an appropriate amount of test sample was added to 0.1 M acetate buffer (pH 4.
0) Dissolve in 100 μl and transfer to a test tube.
0.10 mg of enzyme dissolved in 100 μl (100NF uni
ts), and after incubating at 37 ° C for 20 minutes, the compound 48 / was dissolved in 100 µl of the same buffer.
Add 80 (50 μg) and incubate at 37 ° C. for 20 minutes. Finally, after adding hyaluronic acid sodium salt (200 μg, derived from a microorganism) dissolved in 250 μl of the same buffer and incubating at 37 ° C. for 40 minutes, 100 μl of 0.4N NaOH was added, followed by ice cooling, and then borate buffer (pH 9). 1) Add 100 μl and boil for 3 minutes. After cooling with ice, 3 ml of a p-dimethylaminobenzaldehyde reagent solution was added, and the mixture was incubated at 37 ° C for 20 minutes, and then A585 was measured. As a control, the acetate buffer was used instead of the sample solution. Further, as each blank, the above-mentioned acetate buffer was used instead of the enzyme solution. The inhibitory activity was represented by the inhibition rate calculated from the following formula. A: Control solution A585 B: Control solution blank A585 C: Sample solution A585 D: Sample solution blank A585

[0026]

[Table 1]

Example 6: Tablet 150 g of Sophorae japonica extract (Example 1) was mixed with the same amount of lactose and 5 g of magnesium stearate, and this mixture was tabletted with a single punch tableting machine to give a diameter of 10 mm, Weight 300
mg tablets were produced.

Example 7: Condyle Granules The tablets obtained in Example 6 were crushed, sized and sieved to 20-5.
A 0 mesh granule was obtained.

Example 8: Candy A candy having the following composition was prepared using the extract of Myrica nagi of Example 2. (Composition) (Composition%) Granulated sugar 55.08 Hydro-candy 43.5 Cuenic acid 1.0 Fragrance 0.2 Color element 0.2 Myrica nagi extract of Example 2 0.02

Example 9: Emollient Cream Using the extract of Myrica nagi of Example 2, an emollient cream having the following composition was prepared. (Composition) (Composition%) Beeswax 2.0 Stearyl alcohol 5.0 Stearic acid 8.0 Squalane 10.0 Self-emulsifying propylene glycol monostearate 3.0 Polyoxyethylene cetyl ether (20EO) 1 0.0 Propylene glycol 7.8 Glycerin 4.0 Sodium hyaluronate 0.1 Triethanolamine 1.0 Myricanagi extract of Example 2 0.1 Perfume 0.3 Purified water 57.7

Example 10: Emollient Lotion Using the Sophorae japonica extract of Example 1, an emollient lotion having the following composition was produced. (Composition) (Compound%) Stearic acid 2.0 Cetanol 1.5 Vaseline 3.0 Lanolin alcohol 2.0 Liquid paraffin 10.0 Polyoxyethylene monooleate (10 EO) 2.0 Propylene glycol 4 .8 Glycerin 3.0 Triethanolamine 1.0 Sodium hyaluronate 0.1 Sorbour extract of Example 1 0.1 Fragrance 0.1 Purified water 70.4

Example 11: Shampoo A shampoo having the following composition was prepared using the Parmelia perlata extract of Example 3. (Composition) (Compound%) Lauryl polyoxyethylene (3 mol) sulfuric acid ester triethanolamine salt (40% aqueous solution) 30.0 Lauryl polyoxyethylene (3 mol) sulfuric acid ester sodium salt (40% aqueous solution) 20.0 Lauroyl diethanolamide 4.0 Parmelia perlata extract of Example 3 0.1 Purified water 45.9

Example 12: Toothpaste A dentifrice having the following composition was prepared using the Sophorae japonica extract of Example 1. (Composition) (Compound%) Calcium phosphate dihydrate 42.0 Glycerin 18.0 Carrageenan 0.9 Sodium lauryl sulfate 1.2 Saccharin sodium 0.1 Butyl paraoxybenzoate 0.005 Sophorae japonica extract of Example 1 05 Fragrance 1.0 Purified water 36.745

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Claims (5)

[Claims] 1. Aralia elat
a), Myrica nagi, Parmelia p
erlata and areca
A hyaluronidase inhibitor comprising as an active ingredient an extract of at least one plant or herbal medicine selected from the group consisting of n). 2. The hyaluronidase inhibitor according to claim 1, wherein Taranoki is Soubaku. 3. An anti-inflammatory or anti-allergic agent comprising the hyaluronidase inhibitor according to claim 1 as an active ingredient. 4. A cosmetic containing the hyaluronidase inhibitor according to claim 1. 5. A food containing the hyaluronidase inhibitor according to claim 1.