JP2000086510A - Histamine release inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a histamine release inhibitor derived from a natural product, which has an excellent inhibitory action on histamine which is a chemical mediator of type I allergy, and can effectively prevent and treat allergic diseases. I do. SOLUTION: The histamine release inhibitor of the present invention comprises one or more active ingredients selected from apigenin, chrysoeriol, luteolin and rosmarinic acid. Further, it is preferable to contain an alcohol extract of perilla seed containing one or more selected from apigenin, chrysoeriol, luteolin and rosmarinic acid. Further, it is preferable that the alcohol extract is partitioned between ethyl acetate and water, and the obtained mixture contains an ethyl acetate partition obtained from the ethyl acetate layer. It is desirable to use defatted perilla seeds as the perilla seed. Perilla seeds may be used instead of the perilla seeds. The external preparation for allergy prevention and the food for preventing allergy of the present invention are characterized by containing the histamine release inhibitor.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a histamine release inhibitor, and is applied to, for example, pharmaceuticals, quasi-drugs, cosmetics, foods, etc. for preventing and treating allergic diseases.

[0002]

2. Description of the Related Art In recent years, rapidly increasing allergic diseases are serious social problems with an incidence of over 20%. In particular, hay fever in early spring and atopic dermatitis that spreads from young people to adults are sometimes accompanied by severe symptoms that hinder daily life. Allergy is classified into four types (types I to IV) according to the mechanism of onset. Among them, type I allergy mainly involving immunoglobulin E (IgE) antibody is the most frequently occurring allergy. The process of the onset of type I allergy can be roughly classified into the following three stages. That is, in the first stage, an exogenous antigen enters the body, and an IgE antibody is produced by the immunocompetent cell line. The IgE antibody adheres to mast cells distributed at sites where allergic reactions occur frequently, such as the respiratory tract, skin, and digestive organs, or basophils in the blood, thereby establishing sensitization. In the second stage, the sensitized cells are again contacted with an antigen, and the cells undergo morphological changes such as vacuolation, swelling and degranulation, and histamine, serotonin, SRS-
Releases chemical mediators such as A. In the third stage, the released chemical messenger causes contraction of smooth muscles such as bronchial muscle and gastrointestinal tract, enhancement of capillary permeability, neutrophil migration, aggregation of platelets, and the like. As a result, asthma, Allergic symptoms such as gastrointestinal allergy, nasal allergy, and urticaria accompanied by back pain and diarrhea. For example, itching and redness with blistering on the skin (urticaria), inflammation of the nose and eyes and itching and increased secretion of nasal discharge and tears, or tracheal congestion and difficulty in breathing Symptoms such as seizures (bronchial asthma) are classified as allergic diseases of this type.

[0003]

In order to prevent or treat such a disease caused by type I allergy, studies have recently been made focusing on the histamine release inhibitory action of the second step. That is, by suppressing the release of histamine, the progress of the second stage is suppressed, and various allergic symptoms of the third stage are prevented. For example, tranny, sodium cromoglycate and the like are known as substances having an action of inhibiting histamine release.

The present inventors have conducted various experiments on extracts of perilla seeds, and have found that an ethanol extract of perilla seeds has a strong histamine release inhibitory action. As a result of intensive studies, they have found that apigenin, chrysoeriol, luteolin and rosmarinic acid contained in the alcohol extract of perilla seeds have a histamine release inhibitory effect. In particular, apigenin showed a very excellent histamine release inhibitory action which has never been seen before.

An object of the present invention is to provide a histamine release inhibitor derived from a natural product, which has a very good effect of suppressing the release of histamine which is a type I allergic chemical messenger and can effectively prevent and treat allergic diseases. Is to do.

[0006]

Means for Solving the Problems The histamine release inhibitor of the present invention for solving the above-mentioned problems comprises one or more active ingredients selected from apigenin, chrysoeriol, luteolin and rosmarinic acid. It is characterized by. The histamine release inhibitor of the present invention is apigenin,
It is characterized by containing an alcoholic extract of perilla seed containing one or more selected from chrysoeriol, luteolin and rosmarinic acid. The histamine release inhibitor of the present invention distributes an alcohol extract of perilla seeds containing one or more selected from apigenin, chrysoeriol, luteolin and rosmarinic acid into ethyl acetate and water, and from the ethyl acetate layer It is characterized by containing the obtained ethyl acetate partition.

As the perilla seed, it is desirable to use defatted perilla seed. Perilla seeds may be used instead of the perilla seeds.

[0008] The antiallergic agent of the present invention is characterized by containing the histamine release inhibitor. The external preparation for preventing allergy of the present invention is characterized by containing the histamine release inhibitor. The allergy preventive food of the present invention is characterized by containing the histamine release inhibitor.

As a result of the investigation by the inventors, the antiallergic effect of the extract of Labiatae has been disclosed in Japanese Patent Application Laid-Open No. 9-8718.
No. 9 discloses an antiallergic effect caused by suppression of histamine release in extracts of perilla leaves, flowers, roots and the like (see specification [0021]). However, the histamine release inhibitory substances (apigenin, chrysoeriol, luteolin and rosmarinic acid) contained in the extract of perilla seeds have not been known to inhibit the release of histamine. It was made.

There is a clear difference between perilla seed and leaf extracts in that seeds are rich in aglycone and leaves are rich in glycosides. As seen in the example of perilla leaves,
It is noteworthy that the naturally occurring flavonoids often take the form of glycosides and are abundant in aglycones. In the present invention, the histamine release-inhibiting substances (apigenin, chrysoeriol, luteolin and rosmarinic acid) are efficiently extracted from the seed part, and not only pharmaceuticals but also external preparations (including quasi-drugs and cosmetics) and foods It is possible to mix.

The present inventors also conducted various experiments on perilla seeds classified into the Labiatae genus, the same as perilla seeds, and found that the alcohol extract of perilla seeds also contained a histamine release inhibitor (apigenin). , Chrysoeriol, luteolin and rosmarinic acid). That is, a histamine release inhibitor can be obtained from perilla seeds in the same manner as perilla seeds.

The perilla is an annual plant native to Southeast Asia classified in the Labiatae genus and is an oil crop. It resembles a perilla in its entirety, has a square stem, has oval leaves, and has white florets in summer. Seeds are slightly larger than perilla and are harvested in the fall. Oil obtained from perilla seeds is known as perilla oil or EB oil, and is used as a raw material for food and paint. The oil residue is used as fertilizer and feed. Heretofore, there have been reports on physiologically active substances contained in the leaves of perilla, but few reports on seeds.

The structural formulas of apigenin, chrysoeriol, luteolin and rosmarinic acid are as shown below.

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[0014] Regarding the physiological activity of apigenin, anticancer properties, anti-inflammatory actions and the like are known. Apigenin can be obtained by extracting and purifying sesame and perilla seeds and leaves, and by solvent extraction of Takahashi bracts, seeds and stems.

Regarding the physiological activity of chrysoeriol,
There are only a few reports of anticancer and antibacterial properties.

Luteolin is generally known to exist as a glycoside in leguminous plants (digitalis and the like).
Regarding the physiological activity of luteolin, antioxidant activity, hyaluronidase inhibitory activity and the like are known. Luteolin is
It can be extracted and purified from perilla seeds and perilla seeds and leaves, and also from citrus peels and the like. However, the amount of luteolin contained in the leaves of perilla and perilla is very small, and it is desirable to use these seeds for industrialization.

As for the physiological activity of rosmarinic acid, anti-inflammatory and anti-allergic effects are known. Rosmarinic acid can be obtained by extracting and purifying from the seeds and leaves of perilla or perilla, or by extracting with water-containing alcohol from other Lamiaceae plants.

Using perilla seeds and perilla seeds as raw materials,
The solvent used for extracting apigenin, chrysoeriol, luteolin and rosmarinic acid is preferably ethanol. When ethanol is used, the active ingredient is efficiently extracted, and at the same time, it can be used for both external use and edible use. In addition, as other extraction solvents, ethyl acetate, acetone, methanol,
Butanol and the like can also be used. When alcohol is used as the extraction solvent, the alcohol concentration is desirably adjusted to 70 to 85% (v / v). 7
When the amount is less than 0% (v / v), the amount of the active ingredient extracted becomes insufficient. When the amount exceeds 85% (v / v), the oil content of perilla seeds or perilla seeds easily dissolves in alcohol. Because it becomes. The alcohol extraction is desirably repeated at various concentrations in order to improve the content of the active ingredient.

The alcohol extract of perilla seeds and perilla seeds usually contains all of apigenin, chrysoeriol, luteolin and rosmarinic acid as histamine release inhibitors. However, even if any substance does not exist due to extraction conditions or the like, it is sufficient that at least one or two or more of these substances are contained.

The reason why the alcohol extract of perilla seeds or perilla seeds is distributed between ethyl acetate and water is that these distributions can significantly increase the concentration of the active ingredient. Among the distribution layers, apigenin, chrysoeriol, luteolin and rosmarinic acid are contained at a high concentration in the ethyl acetate layer, and inactive components such as glycosides are transferred to the aqueous layer. Therefore, by separating the ethyl acetate layer, it is possible to efficiently concentrate the active ingredient.

The alcohol extract and the ethyl acetate partition can be used as histamine release inhibitors as they are, but it is possible to purify the active ingredients contained therein. For example, when apigenin is purified, the ethyl acetate layer is subjected to silica gel column chromatography (chloroform: methanol = 10: 1), and the most active fraction is recovered and can be isolated by high performance liquid chromatography.

In the present invention, when perilla seeds or perilla seeds are used, the concentration of the active ingredient can be significantly increased by extracting the defatted product with alcohol. This is because the oil components of perilla seeds and perilla seeds removed by the organic solvent hardly contain physiologically active components such as apigenin and chrysoeriol, and the active components are concentrated in the defatted cake. Hexane is preferably used as an organic solvent for degreasing perilla seeds and perilla seeds.
This is because the extracted oil can be used as an edible oil, and the extract from the defatted residue can be used as a food material or the like. When the extract from the defatted residue is used for purposes other than food, it is not limited to hexane, and it is also possible to use other nonpolar solvents.

Since the histamine release inhibitor of the present invention has an extremely high histamine release inhibitory effect, it is preferably incorporated into pharmaceuticals and the like as an antiallergic agent. Since it is difficult to release histamine from sensitized cells in the onset process of type I allergy, allergic diseases can be effectively treated and prevented.

Further, the histamine release inhibitor of the present invention comprises:
In addition to being used as pharmaceuticals, it can be incorporated into quasi-drugs, cosmetics, foods, and the like. In particular, when a histamine release inhibitor is added to an external preparation such as quasi-drugs or cosmetics or various foods, an antiallergic substance can be easily taken in daily life, which is useful for prevention of allergy.
In addition, long-term administration of the histamine release inhibitor according to the present invention can provide an excellent effect in improving allergic constitution.

When the histamine release inhibitor is used as an external preparation, the form can be arbitrarily selected, for example, creams, ointments, lotions, lotions, emulsions, packs, oils, soaps (including medicated soaps), Face wash, bath agent, shampoo, rinse, spray and the like can be used. In addition, it can be applied to nonwoven fabrics such as sanitary cotton and wet tissue, and can also be used as oral cosmetics such as toothpaste.

When the histamine release inhibitor is used as a food material, confectionery (gum, candy, chocolate, snack, jelly, etc.), noodles (soba, udon, ramen, etc.), soups, beverages (juice, alcohol) , Mineral water, coffee, tea, etc.), health foods, and dietary supplements (nutrition drinks, etc.). Moreover, you may add to instant foodstuffs. For example, a histamine release inhibitor spray-dried or freeze-dried with powdered cellulose can be easily incorporated into a food by forming a powder, granule, tablet or solution.

The method for administering the histamine release inhibitor of the present invention may be either oral or parenteral.
For oral administration, it can be administered as soft or hard capsules or tablets, granules, fine granules, or powders. For parenteral administration, it is administered as a liquid, solid, or suspension viscous liquid. be able to. The method of administration may be local topical administration, intradermal, subcutaneous, intramuscular, or intravenous injection, as well as topical application, topical application, spraying, suppositories, and intravesical injection. . The dose can vary depending on the administration method, medical condition, age of the patient, etc., but in adults, it is usually 0.5 to 5000 as an active ingredient per day.
mg, for children, usually 0.5 to 3000 mg. About the active ingredient concentration of the histamine release inhibitor,
Although it can be appropriately changed depending on the dosage form, usually,
About 0.3- when administered orally or by mucosal absorption
15.0 wt%, 0.01 to parenteral administration
It is good to make it about 10 wt%. In addition, the said dosage is an example and can be changed suitably according to various situations.

The histamine release inhibitor of the present invention may be used as a pharmaceutical,
When blended in quasi-drugs, cosmetics, or food, it can be used in combination with various commonly used components. For example, oils (animal and vegetable oils, mineral oils, ester oils, wax oils, silicone oils, higher alcohols, phospholipids, fatty acids, etc.), surfactants (anionic, cationic, amphoteric or nonionic), vitamins (vitamin A, B, C,
D, E, folic acid, nicotinic acid, pantothenic acid, bitione), ultraviolet absorber (p-aminobenzoic acid, anthranil, salicylic acid, coumarin, benzotriazole, tetrazole, imidazoline, pyrimidine, dioxane, furan, pyrone, camphor, nucleic acid , Allantoin and derivatives thereof, amino acid compounds, shikonin, baicalin, baicalein, berberine, etc.), antioxidants (stearic acid ester, nordihydroguaselthenic acid, dibutylhydroxytoluene, butylhydroxyanisole, parahydroxyanisole, gallic acid) Propyl, sesamol, sesamolin, gossypol, etc.), thickeners (hydroxyethyl cellulose, ethyl cellulose, carboxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, carbo) Sodium methyl methyl cellulose, hydroxypropyl cellulose, nitrocellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, carboxyvinyl polymer, gum arabic, tragacanth gum, agar, casein, dextrin, gelatin, pectin, starch , Alginic acid and its salts), humectants (propylene glycol, 1,
3-butylene glycol, polyethylene glycol, glycerin, chondroitin sulfate and its salts, hyaluronic acid and its salts, sodium lactate, etc.), other lower alcohols, polyhydric alcohols, water-soluble polymers, pH adjusters, preservatives, coloring agents Fragrances, fresheners, stabilizers, animal and plant extracts (ferulic acid, γ-oryzanol, etc.), animal and plant proteins and their degradation products, animal and plant polysaccharides and their degradation products, animal and plant products Glycoproteins and their degradation products, microbial culture metabolites, blood flow enhancers, anti-inflammatory agents, cell activators,
It can be used in combination with amino acids and their salts, keratolytic agents, astringents, wound healing agents, foam enhancers, oral agents, deodorants and deodorants.

[0029]

The type I allergy is caused by the release of histamine accompanying morphological changes such as vacuolation, swelling and degranulation of sensitized cells. Allergic reactions can be significantly reduced. Therefore, the histamine release inhibitor of the present invention can effectively treat or prevent hay fever, asthma, hay fever, rhinitis, urticaria, drug allergy, etc., which are symptoms of type I allergy. In addition, the external preparation for allergy prevention and the food for preventing allergy containing the histamine release inhibitor of the present invention can prevent allergy in daily life and easily improve the constitution.

[0030]

Embodiments of the present invention will be described below. [Preparation of Histamine Release Inhibitor] As shown in FIG. 1, crushed perilla seed was first refluxed with hexane, and then the residue (defatted product) was refluxed with 80% (v / v) ethanol. Next, the ethanol extract obtained by refluxing 80% (v / v) ethanol was mixed with hexane and 80% (v / v).
After partitioning with methanol and evaporating the solvent of this methanol layer,
Further, the mixture was partitioned between ethyl acetate and water. After separating the ethyl acetate layer and the aqueous layer, the solvent of the ethyl acetate layer was distilled off to obtain an ethyl acetate partition.

Next, this ethyl acetate partition was subjected to silica gel column chromatography (chloroform: methanol = 10: 1) to separate fractions 1 to 3. Among these, the fraction 1 eluted first was subjected to high performance liquid chromatography to isolate chrysoeriol and apigenin. The fraction 2 to be eluted next was suspended in a mixed solvent (chloroform: methanol = 15: 1), and luteolin was isolated from the insoluble fraction. Further, for the fraction 3 eluted last, rosmarinic acid was isolated by high performance liquid chromatography.

Example 1 was obtained by distilling off the ethanol extract shown in FIG. 1 as a solvent. The ethanol extract was partitioned with ethyl acetate / water, and acetic acid obtained by distilling off the solvent from the ethyl acetate layer and the aqueous layer was obtained. The ethyl partition and the water partition were used as Example 2 and Comparative Example 1. Further, purified products of apigenin, chrysoeriol, luteolin, and rosmarinic acid isolated from the ethyl acetate partition were designated as Examples 3 to 6, respectively. In Examples 1 to 6, an extract obtained from perilla seeds was used as a histamine release inhibitor. However, the same ratio of components as in Examples 1 to 6 was obtained from perilla seeds in the same manner. A histamine release inhibitor can be obtained.

[Histamine Release Inhibition Test] Next, in Examples 1 to 6, the effect of inhibiting histamine release was tested. (1) Test method The intraperitoneal fluid of male Wistar rats that had been bled to death was used.
It was adjusted to × 10 ⁴ / ml and suspended in a Tyrode-HEPES buffer (pH 7.4) (cell suspension). To 0.7 ml of the cell suspension, 50 μl of the sample solution was added to add 37 μl.
After incubation for 5 minutes at 40 ° C., 40 μg / ml C
Add 50 μl of OMPOUND48 / 80, and for 1 minute,
The reaction was performed at 37 ° C. Immediately after completion of the reaction, histamine was extracted and purified from the ice-cooled and centrifuged supernatant, and o-phthalaldehyde was added to measure the fluorescence intensity (excitation wavelength 3).
55 nm, fluorescence wavelength 450 nm). Based on the measured value of the fluorescence intensity, the histamine release inhibition rate was calculated by the following equation. Suppression rate (%) = {1− (SB) / (CB)} × 10
0 B: Amount of histamine released from unstimulated cells C: Amount of histamine released when COMPOUND48 / 80 is added S: Amount of histamine released by COMPOUND48 / 80 in the presence of sample

(2) Concentration of Example 1 (Ethanol Extract)
Change in histamine release inhibition rate with respect to change in degree In Example 1, the effect of inhibiting histamine release with respect to concentration change was investigated. The sample solutions of Example 1 were adjusted to various concentrations, and the histamine release inhibition rates of these sample solutions were calculated by the test method. The results are shown in FIG.

As shown in FIG. 2, Example 1 (ethanol extract of perilla seed) exhibited a concentration-dependent histamine release inhibitory action. From FIG. 2, the IC ₅₀ is 5
It was calculated to be 0.0 μg / ml.

(3) Example 1 (ethanol extract) and
And Example 2 (Ethyl acetate partition) inhibit histamine release
Comparison of effects Next, Example 1 and Example 2 were tested for differences in histamine release inhibiting activity. Example 1 and Example 2
Was set to 125 μg / ml, and the histamine release inhibition rate was calculated by the test method. As a comparative example, a water partition of ethyl acetate shown in FIG. 1 (Comparative Example 1)
For, the histamine release inhibition rate was calculated under the same conditions. The results are shown in FIG.

As shown in FIG. 3, Example 1 (ethanol extract) exhibited a histamine release inhibition rate of 67% at a concentration of 125 μg / ml, whereas Example 2 (ethanol extract) exhibited a histamine release inhibition rate of 67%.
(Ethyl acetate partition) has a histamine release inhibition rate of 97%.
%showed that. This is because in Example 2 (ethyl acetate partition), apigenin, which is effective as a histamine release inhibitor,
It is considered that chrysoeriol, luteolin and rosmarinic acid were concentrated at a high concentration. In addition, since the inactive component contained in the ethanol extract was distributed to the water partition (Comparative Example 1), it is considered that the histamine release inhibition rate was lower than those in Examples 1 and 2.

(4) Example 3 (purified apigenin), fruit
Example 4 (purified chrysoeriol), Example 5 (Luteo
(Purified phosphorus) and Example 6 (purified rosmarinic acid)
Histamine release inhibitory effect The purified histamine release inhibitory effect of four purified polyphenols (apigenin, chrysoeriol, luteolin and rosmarinic acid) of Examples 3 to 6 was tested. As comparative examples, quercetin (Comparative Example 2), caffeic acid (Comparative Example 3) and catechin (Comparative Example 4), which are typical polyphenols derived from natural products, and sodium cromoglycate (Comparative Example 5) which is an antiallergic agent Was also tested for histamine release inhibitory activity under the same conditions.
The sample solutions of Examples 3 to 6 and Comparative Examples 2 to 5 were prepared at 125 μg / ml, and the histamine release inhibition rate was calculated by the test method.

As shown in FIG. 4, in Example 6 (purified rosmarinic acid), compared with Comparative Example 4 (catechin),
Although the histamine release inhibition rate was inferior, Examples 1 to 3 exhibited a superior histamine release inhibition rate than Comparative Examples 2 to 5. In particular, Example 3 (purified apigenin) exhibited a histamine release inhibitory rate of about 2.5 times that of Comparative Example 4 (catechin).

[Application to External Formulation for Prevention of Allergy] Next, an example in which the histamine release inhibitor of the present invention is applied to an external preparation for preventing allergy will be described. In the following table, “Ethanol extract of perilla seed” and “Ethanol extract of perilla seed” are obtained by drying the ethanol extract obtained under the same extraction conditions as in Example 1 above to obtain a powder. is there.
In addition, the “ethyl acetate partition of perilla seed” and the “ethyl acetate partition of perilla seed” are obtained by drying and powdering the ethyl acetate partition obtained under the same extraction conditions as in Example 2. . Formulation Example 1: Emulsion wt% squalane 5.0 Olive oil 5.0 Jojoba 5.0 Cetyl alcohol 1.5 Glycerin monostearate 2.0 Polyoxyethylene (20) cetyl ether 3.0 Polyoxyethylene (20) sorbitan mono Olate 2.0 1,3-butylene glycol 1.0 Glycerin 2.0 Water 68.5 Ethanol extract of perilla seeds 5.0 Perfume, preservatives

Formulation Example 2: Peel-off pack wt% glycerin 5.0 Propylene glycol 4.0 Polyvinyl alcohol 15.0 Ethanol 8.0 Polyoxyethylene glycol 1.0 Emmeiso 5.0 Water 57.0 Ethanol extract of perilla seed 5.0 Appropriate amount of fragrance and preservative

Formulation Example 3: Cold cream wt% beeswax 11.0 Liquid paraffin 26.0 Lanolin 10.0 Almond oil 15.0 Borax 0.5 Water 34.5 Ethyl acetate distribution of perilla seed 3.0 Fragrance Appropriate amount Preservative Appropriate amount

Formulation Example 4: Shampoo wt% triethanolamine lauryl sulfate 5.0 sodium polyoxyethylene lauryl ether sulfate 12.0 1,3-butylene glycol 4.0 lauric acid diethanolamide 2.0 disodium edetate 0. 1 Water 73.9 Ethyl acetate partition of sesame seed 3.0 Spices Appropriate Preservatives Appropriate

Formulation Example 5: Body soap wt% potassium laurate 15.0 potassium myristate 5.0 propylene glycol 5.0 water 72.0 purified apigenin 3.0 pH adjuster proper amount preservative proper amount

Formulation Example 6: Rinse wt% Stearyltrimethylammonium chloride 2.0 Cetostearyl alcohol 2.0 Polyoxyethylene lanolin ether 3.0 Propylene glycol 5.0 Water 84.0 Purified chrysoeriol 4.0 pH adjustment Agent appropriate amount preservative appropriate amount

Formulation Example 7: Hair liquid wt% ethanol 29.0 Polyoxyfluorophenylethyl ether phosphate 10.0 Polyoxyfluorophenyl monobutyl ether 5.0 Triethanolamine 1.0 Water 50.0 Luteolin purified product 5.0 Preservative Appropriate amount

Formulation Example 8: Hair tonic wt% ethanol 40.0 Ethyl oleate 1.0 Polyoxyethylene (40) hydrogenated castor oil 2.0 Water 52.0 Purified rosmarinic acid 5.0

Formulation Example 9: Granule bath preparation wt% sodium bicarbonate 60.0 Anhydrous sodium sulfate 32.0 Borax 3.0 Ethyl acetate distribution of perilla seed 1.0 Alcohol extract of perilla seed 4.0

Formulation Example 10: Toothpaste wt% calcium carbonate 50.0 glycerin 20.0 carrageenan 0.5 carboxymethylcellulose 1.0 lauryldiethanolamide 1.0 sucrose monolaurate 2.0 fragrance 1.0 saccharin 1 Water 24.1 Ethyl acetate partition of perilla seed 0.1 Ethanol extract of perilla seed 0.2

Formulation Example 11: Mouthwash wt% ethanol 20.0 Fragrance 1.0 Lauryldiethanolamide 0.3 Sodium monofluorophosphate 0.1 Saccharin sodium 0.05 Water 77.55 Apigenin purified product 0.3 Luteolin purification Thing 0.7

Formulation Example 12: Tablet for gargle wt% sodium bicarbonate 54.0 citric acid 17.0 anhydrous sodium sulfate 12.8 dibasic sodium phosphate 10.0 polyethylene glycol 3.0 sodium monofluorophosphate 0.1 Perfume 2.0 Oleic acid 0.1 Purified chrysoeriol 0.5 Rosmarinic acid purified 0.5

The external preparations for preventing allergies shown in the above Formulation Examples 1 to 12 are useful for treating diseases caused by type I allergy when antiallergic substances (apigenin, chrysoeriol, luteolin, rosmarinic acid) are taken into the body through the skin and the like. Can be prevented. In particular, when a histamine release inhibitor is blended with an externally used preparation such as an emulsion or a bath preparation which is used relatively frequently, an excellent antiallergic effect can be expected.

[Application to Allergy Prevention Foods] An example in which the histamine release inhibitor of the present invention is applied to allergy prevention foods will be described. In the following table, “Ethanol extract of perilla seed” and “Ethanol extract of perilla seed” are obtained by drying the ethanol extract obtained under the same extraction conditions as in Example 1 above to obtain a powder. is there. Formulation Example 13: Chewing gum wt% gum base 25.0 Glucose 24.0 Sugar 48.0 Fragrance 1.0 Ethanol extract of perilla seed 2.0

Formulation Example 14: Chewing gum wt% gum base 20.0 glucose 10.0 sugar 51.5 starch syrup 16.0 fragrance 0.5 ethanol extract of perilla seed 2.0

Formulation Example 15: Candy wt% sugar 50.0 Ginger syrup 33.0 Organic acid 2.0 Fragrance 0.2 Water 14.4 Ethanol extract of perilla seed 0.4

Formulation Example 16: drop wt% sugar 58.0 syrup 40.0 organic acid 1.0 purified apigenin 1.0 flavor appropriate amount pigment appropriate amount

Formulation Example 17: Chocolate wt% Vita chocolate 18.0 Cocoa butter 16.5 Powdered sugar 42.0 Full-fat powdered milk 22.0 Lentin 0.5 Chrysoeriol purified product 1.0 Perfume Appropriate amount

Formulation Example 18: Caramel wt% sugar 39.0 Mizuame 38.0 Condensed milk 15.5 Flour 5.0 Butter 0.5 Shortening oil 1.0 Luteolin refined product 1.0 Perfume Appropriate amount

Formulation Example 19: Jelly wt% sugar 38.0 Mizuame 42.5 Agar 1.5 Glucose 5.0 Water 12.0 Rosmarinic acid purified product 1.0 Colorant / flavor

Formulation Example 20: Yogurt wt% skim milk 88.0 Skim milk powder 0.5 Sucrose 10.0 Natural fruit juice 1.0 Ethanol extract of perilla seed 0.5 Appropriate amount of coloring and flavoring

Formulation Example 21: Biscuit wt% flour 67.5 Sugar 10.0 Shortening 15.0 Salt 1.0 Swelling agent 1.0 Invert sugar 5.0 Ethanol extract of perilla seed 0.5

According to the allergy preventive foods of Formulation Examples 13 to 21, the antiallergic substances (apigenin, chrysoeriol, luteolin, rosmarinic acid) can be easily taken, and the disease caused by type I allergy can be effectively prevented. Can be prevented.

[Brief description of the drawings]

FIG. 1 is a process diagram illustrating a method for preparing a histamine release inhibitor according to an example of the present invention.

FIG. 2 is a characteristic diagram showing a change in a histamine release inhibitory rate with respect to a change in the concentration of a perilla seed ethanol extract according to an example of the present invention.

FIG. 3 is a graph showing the histamine release inhibition rates of various partitions of perilla seed ethanol extract according to an example of the present invention.

FIG. 4 is a graph showing the histamine release inhibition rates of various purified products according to Examples and Comparative Examples of the present invention.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) A23L 1/30 A23L 1/30 B 4C083 A61K 7/00 A61K 7/00 K 4C086 W 4C088 U 4C206 7/06 7/06 7/26 7/26 7/48 7/48 7/50 7/50 31/235 ABF 31/235 ABF 35/78 AED 35/78 AEDQ // A23C 9/123 A23C 9/123 C07D 311/30 C07D 311 / 30 (72) Inventor Tadashi Okada Within Ichinomiya-city, Aichi Prefecture, northern character Numata Ichibanchi, Orisa Petrochemical Co., Ltd. In-house F-term (reference) 4B001 AC21 EC99 4B014 GB01 GB06 GB13 GG09 GG18 GK12 GL03 4B018 LB01 LB02 LB07 LB08 MD08 MD56 MD61 ME07 4B032 DB21 DK05 DK29 DK30 DL20 DP08 4C062 EE54 4C083 AA08A AB122 AA112 AB122 A102 AC122 AC182 AC242 AC252 AC302 AC341 AC342 AC352 AC402 AC422 AC432 AC532 AC542 AC6 42 AC692 AC782 AC841 AC842 AC862 AC902 AD042 AD112 AD222 AD272 AD352 AD512 BB51 CC05 CC07 CC23 CC25 CC32 CC37 CC38 CC39 CC41 DD15 DD16 DD22 DD23 DD27 DD31 EE13 EE21 EE22 EE31 EE41 4C086 AA01 AA02 BA08 MA17 MA03 MA03 MA03 MA03 MA03 MA03 MA08 ZA36 ZA54 ZA59 ZA66 ZA72 ZA89 ZB13 ZC13 ZC14 ZC41 4C088 AB38 AC04 BA10 BA11 BA31 MA01 MA52 MA63 NA14 ZA08 ZA33 ZA34 ZA36 ZA54 ZA59 ZA66 ZA72 ZA89 ZB13 ZC13 ZC14 ZC41 MA02 AA13 MA02 MAA ZA66 ZA72 ZA89 ZB13 ZC13 ZC14 ZC41

Claims (8)

[Claims] 1. A histamine release inhibitor comprising one or more active ingredients selected from apigenin, chrysoeriol, luteolin and rosmarinic acid. 2. A histamine release inhibitor comprising an alcoholic extract of perilla seed containing one or more selected from apigenin, chrysoeriol, luteolin and rosmarinic acid. 3. An alcohol extract of perilla seeds containing one or more selected from apigenin, chrysoeriol, luteolin and rosmarinic acid, is partitioned between ethyl acetate and water, and ethyl acetate obtained from the ethyl acetate layer. A histamine release inhibitor comprising a partition. 4. The histamine release inhibitor according to claim 2, wherein a defatted perilla seed is used as the perilla seed. 5. The histamine release inhibitor according to claim 2, wherein perilla seeds are used in place of the perilla seeds. 6. An antiallergic agent comprising the histamine release inhibitor according to any one of claims 1 to 5. 7. An external preparation for preventing allergy comprising the histamine release inhibitor according to any one of claims 1 to 5. 8. An allergy preventive food comprising the histamine release inhibitor according to any one of claims 1 to 5.