JPH10287582A - Suppressant for liberation of histamine comprising bark extract - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a plant extract having suppressing actions on the liberation of histamine with slight adverse effects. SOLUTION: This suppressant for the liberation of histamine comprises a bark extract obtained by extracting a bark of a tree selected from Cinnamomum loureirii Nees, Myrica rubra Sieb. et Zucc., Cinnamomum sericeum Sieb. Ficus wightiana Wall., Cinnamomum japonicus Sieb., Betula ermanii. Cham. var. ermanii, Sorbus commixta Hedlund var. commixta, Betula platyphylla Sukatchev var. japonica (Mq.) Hara or Salix bakko Kimura with a polar solvent. Water, a hydrous ethanol, acetone, etc., are used as the polar solvent. The suppressant is effective in alleviating various symptoms of allergic diseases such as atopic dermatitis, bronchial asthma or pollinosis. Since there is a slight fear of adverse effects, the extract can be used as a medicine or formulated with a cosmetic, a bathing agent or a food for use.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a histamine release inhibitor comprising a bark extract. The histamine release inhibitor of the present invention has an excellent effect on alleviating various symptoms of allergic diseases such as atopic dermatitis, bronchial asthma, and hay fever caused by release of histamine.

[0002]

2. Description of the Related Art In recent years, bronchial asthma, allergic rhinitis,
The increase in allergic diseases such as hay fever has become a social problem. According to the Ministry of Health and Welfare (Allergy Research) report in 1995, the prevalence of allergic diseases in elementary and junior high school students was 37.8.
%, And is expected to increase further in the future. The mechanism of allergy is that when an allergen (pollen or tick) enters the body, an antibody IgE that causes allergy is produced and tightly binds to the surface of mast cells everywhere in the body. This is the state of preparation for allergy. Mast cells are packed full of granules containing toxic amine compounds such as histamine. When the allergen enters the body again and reacts with IgE antibodies bound to mast cells in the respiratory tract and mucous membranes, intracellular granules are destroyed and histamine is released. Histamine causes eczema such as hives, asthma, and increased exocrine secretions such as tears and nasal discharge. As a treatment for allergies,
First, there are three things: to prevent the production of IgE antibodies, to suppress the release of chemical substances from mast cells, and to block the action of histamine such as an antihistamine at the terminal. A method for treating allergy by suppressing the release of histamine from mast cells by administering a histamine release inhibitor has been performed. As such a drug, synthetic drugs such as ketotifen and oxatomide are known.

[0003]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies to find a natural product of a plant, unlike synthetic drugs, which has relatively little risk of side effects and has an action of inhibiting histamine release. , The bark extract of certain plants,
The inventors have found that the release of histamine from mast cells is suppressed and that no special side effects are observed, and the present invention has been completed.

[0004]

SUMMARY OF THE INVENTION The present invention relates to a Nikkei (Ci)
nnamomum loureirii Nees), Bayberry (Myrica rubraSi)
eb. et Zucc), Malvanickei (Cinnamomum sericeum)
Sieb.), Akou (Ficus wightiana Wall.), Yabunikei (Cinnamomum japonicus Sieb.), Betulka (Betul)
ermanii), rowan (Sorbus)
commixta), Birch (Betula)
platyphylla Sukatshev var. japonica (Mq.) Hara) or a histamine release inhibitor consisting of a bark extract obtained by extracting the bark of a tree selected from a wild willow (Salix bakko Kimura) with a polar solvent. All of the trees used as raw materials in the present invention can be easily obtained because they are native or cultivated in Japan.

In preparing the bark extract of the present invention, the bark of the above tree is cut into pieces, dried, and preferably further ground, and then extracted by adding 5 to 10 times the amount of a polar solvent. As the polar solvent, water or an organic solvent having a relatively low boiling point that can be easily removed by distillation after extraction is used.
Specific examples of the organic solvent include methanol, ethanol,
Acetone, ethyl acetate and the like, and a mixed solvent of these with water are exemplified.

[0006] The extraction is carried out at room temperature to the reflux temperature while shaking or stirring with adding a solvent to the ground tree bark. The time required for extraction depends on the temperature, the type of bark and the state of grinding, but is usually about 30 minutes to 5 hours. It is also effective to increase the extraction efficiency by destroying the tissue by treatment with an enzyme such as cellulase or hemicellulase at the time of extraction. The extract is filtered or centrifuged to remove solids,
The extraction solvent is distilled off by a suitable method known per se, and the obtained residue may be used as it is as a histamine release inhibitor, or may be used after being concentrated or dried. If desired, the extract may be decolorized with activated carbon,
It may be purified by resin treatment of a synthetic polymer adsorbent or the like. For example, the extract can be purified by subjecting it to column chromatography on a styrene-divinylbenzene copolymer-based polymer adsorbent and eluting with water, 20 to 50% ethanol, ethanol, or the like. However, the histamine release inhibitory action of the active ingredient is strongly exhibited even in the form of the extract, so that high-level purification is not usually required unless it is inconvenient in terms of color, odor, stability and the like.

[0007] The histamine release inhibitor of the present invention can be used as a pharmaceutical or in a cosmetic, bath or food. When used as a medicament, it is mixed with excipients and the like, formulated as tablets, powders, granules, capsules, and extracts, and administered orally, or transdermally as an ointment Is done.

The amount of the histamine release inhibitor of the present invention varies depending on the form of the histamine release inhibitor, the expected effect, and the like. Usually, the extract is used in an amount of from 0.01 to 0.01% based on the total amount of the preparation. 10.0% by weight, preferably 0.1 to 5.
0% by weight is suitable. When the histamine release inhibitor of the present invention is incorporated into cosmetics or baths, a base (eg, petrolatum, liquid paraffin, etc.), a thickener (eg, carboxyethylcellulose, hyaluronic acid, etc.), a surfactant (eg,
Auxiliary components such as polyoxyethylene hydrogenated castor oil, sodium lauryl sulfate, etc.), diluents (eg, water, ethanol, etc.), preparation carriers such as fragrances, excipients, and additives can be mixed. The histamine release inhibitor of the present invention,
A formulation such as an ointment, an emulsifier, a cream, a lotion, a powder, a pack or the like can be made by a method known per se.

Further, when the histamine release inhibitor of the present invention is incorporated into a food, it is added to cookies, biscuits,
It can be added to confectionery such as gum, soft drinks, dairy products, and even staple foods. In mixing these foods, appropriate additives such as bulking agents, flavoring agents, and excipients can be optionally added as needed.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[Examples] Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but the present invention is not limited thereto.

Example 1 Preparation Example of Bark Extract As a raw material, 442 g of ground birch bark was statically extracted twice with 3.0 L of 70% acetone. Then, the combined liquid of the two extracts was concentrated under reduced pressure to about 1.0 liter,
Lyophilization yielded 80 g of a light brown powder. The birch bark extract thus obtained has the following physicochemical properties. Solubility: Easily soluble in methanol, ethanol and aqueous acetone Insoluble in benzene, ether and chloroform Ultraviolet absorption spectrum: (MeOH) λmax: 280, 204 Color reaction: Colors greenish brown with ferric chloride and adds alkali And reddish brown. Thin Layer Chromatography (TLC) Using a Kieselgel 60F254, 0.25 mm thin plate manufactured by Merck, when the developing solvent is ethyl acetate: chloroform: methanol: water = 8: 4: 4: 1, the following Rf value and color are shown. . Rf value color ( Dark sulfuric acid) 0.387 Brown 0.437 〃 0.463 Blue purple 0.538 Yellow 0.725 Red brown 0.775

Example 2 Production Example of Bark Extract As a raw material, 100 g of ground birch bark was statically extracted twice with 1.0 liter of 60% ethanol. Then 2
The combined liquid of the extracts was concentrated under reduced pressure to about 0.5 liter and freeze-dried to obtain 15 g of a light brown powder.

Test Example 1 Histamine Release Inhibition Test Each bark extract produced in the same manner as in Example 1
The histamine release inhibitory activity was measured. Test method: Peritoneal cells were collected from rat abdominal cavity and
Mast cells were isolated at 95% purity by density gradient centrifugation. The test sample was placed in a physiological salt solution (154 mM NaCl, 2.7 mM KC
1, 0.9 mM CACl ₂ , 5 mM HEPES, 0.1% glucose; pH 7.4)
And then add mast cells, 37 ° C., 20
Preincubation was performed for a minute. Next, compound48 / 8
0 (0.5 μg / ml) and add i
Histamine release was induced by ncubation. After stopping the reaction by ice cooling, the reaction was centrifuged, and the amount of histamine released in the supernatant and the amount of histamine in the residue were quantified using an autoanalyzer. Table 1 shows the results. The results were expressed as histamine release rate. The histamine release inhibitory effect of the birch extract is further shown in FIG.

[0014]

[Table 1]

Example 3 Example of Concentration of Active Ingredient 75 g of the powder obtained in Example 1 was suspended in water, insolubles were filtered off, and then the filtrate was treated with Diaion (DI, manufactured by Mitsubishi Kasei Corporation).
Column chromatography of AION HP-20 (φ50 × 300m)
m) and eluted sequentially with water, 20% ethanol, 50% ethanol, ethanol (2 liters each), collect the fractions, concentrate under reduced pressure, and extract 16.0 g of water-eluting extract, 20
% Ethanol eluted extract 20.0 g, 50% ethanol eluted extract 28.0 g and ethanol eluted extract 5.0
g was obtained. A test according to Test Example 1 was performed for each extract. The results are shown in FIGS.

Formulation Example 1 Candies were prepared according to the formula shown in the following table. That is, sugar and starch syrup were dissolved by heating at 150 ° C., cooled to 120 ° C., the remaining components were added, the mixture was stirred and homogenized, and then molded and cooled to obtain a candy. Candy sugar 120.0 Candy sugar 100.0 Citric acid 4.0 Flavors 0.4 Ethanol extract of birch bark 0.1 Total 20.0 (g)

Formulation Example 2 The following ingredients were mixed, molded, and fired to obtain a biscuit. Biscuits Strong flour 100.0 Light flour 30.0 Upper sugar 40.0 Shortening 100.0 Baking soda 0.6 Full fat milk powder 4.0 Water 20.0 Ethanol extract of birch bark 1.0 Total 360. 0 (g)

Formulation Example 3 The remaining ingredients were added to a gum base according to the following formula, and the mixture was stirred and homogenized to obtain a chewing gum. Chewing gum Gum base 100.0 Citric acid 1.0 Fragrance 1.0 Ethanol extract of Nikkei bark 0.1 Total 100.0 (g)

Formulation Example 4 Glycerin is dissolved in purified water. The remaining components were separately mixed, added to the purified aqueous solution, and filtered to obtain a lotion. Of粧water Glycerin 6.0 Ethanol 9.0 Polyoxyethylene hydrogenated castor oil 0.8 Methyl paraben 0.05 Sodium citrate 0.05 Citric acid 0.07 Perfume 0.1 birch bark ethanol extract 1.0 seminal Water production balance 100.0 (g)

Formulation Example 5 A birch bark extract and decaglyceryl stearate were dissolved by heating and added gradually to a mixture of dextrin and talc with stirring to obtain a cosmetic powder. Cosmetic powder dextrin 2.0 talc 96.0 decaglyceryl stearate 1.0 ethanol extract of birch bark 1.0 total 100.0 (g)

Formulation Example 6 Birch bark extract, ethyl paraben, fragrance and ethanol were uniformly dissolved. This was added to a mixture of vinyl acetate / styrene copolymer, polyvinyl alcohol and sorbite to obtain a cosmetic pack. Cosmetic pack Vinyl acetate / styrene copolymer 10.0 Polyvinyl alcohol 10.0 Sorbit 5.0 Ethanol 5.0 Fragrance 2.0 Ethylparaben 0.2 Ethanol extract of birch bark 1.0 Refined water balance 100.0 (g)

Formulation Example 7 The components of the following formulation were stirred and homogenized to obtain a bath agent. Bath agent (granule type) Sodium sulfate 50.0 Sodium hydrogen carbonate 49.0 Sodium CMC 0.9 Ethanol extract of birch bark 0.1 Total 100.0 (g)

Formulation Example 8 The ingredients of the following formulation were stirred and homogenized to obtain a bath agent. Bath agent (liquid milk bath type) Liquid paraffin 60.0 Squalane 10.0 Vegetable oil 14.0 Sorbitan oleate 5.0 POE oleyl ether 10.0 Ethanol extract of birch bark 0.1 Refined water 0.9 Total 100.0 (g)

[0024]

The histamine release inhibitor of the present invention effectively suppresses the release of histamine from mast cells. Therefore, it is useful for alleviating the symptoms of allergic diseases such as atopic dermatitis, bronchial asthma and hay fever caused by release of histamine. In addition, since it is an extract of tree bark, there is little risk of side effects, and it can be used as a medicine, or blended in cosmetics, bath preparations, and foods.

[Brief description of the drawings]

FIG. 1 is a graph showing the histamine release inhibitory effect of a birch bark extract.

FIG. 2 is a graph showing the histamine release inhibitory effect of birch bark extract subjected to column chromatography and eluted with various solvents, (1) is a water eluent, (2) is 2
The 0% ethanol eluent is shown.

FIG. 3 is a graph showing the histamine release inhibitory effect of a birch bark extract subjected to column chromatography and eluted with various solvents. (1) is a 50% ethanol eluent, and (2) is an ethanol eluent. The histamine release inhibitory effect is shown respectively.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/00 A61K 7/00 K W 7/48 7/48 7/50 7/50 // A21D 2/36 A21D 2/36 A23G 3/00 101 A23G 3/00 101 3/30 3/30 (72) Inventor Izumi Hatanaka 1-1-1 Tsushimanaka, Okayama City, Okayama Pref. 1-1-1 Naka Okayama University Faculty of Pharmaceutical Sciences

Claims (6)

[Claims] Claims: 1. Nikkei, bayberry, malvanickei,
A histamine release inhibitor comprising a bark extract obtained by extracting a bark of a tree selected from ako, yabnikkei, birch birch, rowan, birch or wild willow with a polar solvent. 2. The histamine release inhibitor according to claim 1, wherein the polar solvent is one or more solvents selected from water, methanol, ethanol, isopropanol, butanol, butylene glycol and acetone. 3. The histamine according to claim 1, which is obtained by subjecting the bark extract to column chromatography on a styrene-divinylbenzene copolymer-based polymer adsorbent and eluting with water, 20 to 50% aqueous ethanol or ethanol. Release inhibitors. 4. A cosmetic containing the histamine release inhibitor according to any one of claims 1 to 3. 5. A bath containing the histamine release inhibitor according to any one of claims 1 to 3. 6. A food containing the histamine release inhibitor according to any one of claims 1 to 3.