JP2001278792A - Anti-allergic and anti-inflammatory agent, medicinal composition, quasi drug, cosmetic material, food and animal feed containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a more effective anti-allergic and antiinflammatory agent by utilizing a highly safe proanthocyanidin. SOLUTION: This anti-allergic and anti-inflammatory agent is provided by using proanthocyanidin having >=3,000, desirably >=3,000 and <=10,000 molecular weight among the proanthocyanidin having a wide molecular weight distribution, which is found out to have a potent activity of inhibitory effect for releasing chemical mediators such as histamine, serotonin, etc., inhibit the flow of Ca2+ into mast cell and/or basophile mediated through a Ca2+ channel and/or induce NO production in the mast cell and/or basophile, and by these mechanisms inhibit cell degranulation for inhibiting, as a result, the release of the chemical mediators such as histamine, serotonin, leukotriene, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an antiallergic agent, an antiinflammatory agent containing proanthocyanidin as an active ingredient, and a pharmaceutical composition, quasi-drug, cosmetic, food and animal feed containing the same.

[0002]

2. Description of the Related Art Proanthocyanidins are condensed tannins present in various plants, and are a group of compounds formed by condensing or polymerizing flavan-3-ol or flavan-3,4-diol as a structural unit. These produce cyanidin, delphinidin, anthocyanidin such as pelargonidin by acid treatment,
This is the name given. And a dimer, trimer, tetramer and 10 to 100-mer or more of the above-mentioned structural units, procyanidin, prodelphinidin,
It includes proanthocyanidins such as properargonidin and their stereoisomers, their gallic esters and the like, and is a group of compounds having a very wide molecular weight distribution of about 600 to 500,000 in terms of molecular weight.

[0003] The allergic reaction is caused by release of inflammatory substances such as histamine and serotonin from mast cells and / or basophils upon allergen stimulation, or cytokines released as a result of macrophage activation by activated T cells. Various inflammations occur. Therefore, it has been proposed to use naturally occurring proanthocyanidins as anti-allergic agents as a mechanism by suppressing the release of inflammatory substances such as histamine and serotonin from mast cells or basophils [ "OPC in practice biofla
vanols andtheir applicati
on, "Alfa Omega, 1993, p.
8-56].

[0004] Immediate type allergy, which is one of the allergic reactions, is that antigen-specific IgE is produced by B cells upon invasion of antigen, and this is produced by mast cells and / or basophil Ig.
Binding to the E receptor, and then binding of the antigen to this IgE receptor-antigen complex signals intracellularly to the Ca
Inflow of Ca ²⁺ from the ²⁺ channel occurs as an initial reaction, further degranulation occurs through phosphorylation of various protein kinases, enzymes such as β-hexosaminidase, histamine, serotonin, etc. Chemical mediators (inflammation-causing substances) are released, and various allergic reactions and inflammation are caused by the released chemical mediators such as histamine and serotonin.

[0005] In delayed allergy, C
Ca ²⁺ influx from the a ²⁺ channel occurs as an initial reaction. Therefore, in mast cells and / or basophils, C
If a compound that suppresses the influx of Ca ²⁺ from the a ²⁺ channel can be found, allergic reactions or inflammation can be controlled.

Recently, it has been reported that nitric oxide (NO) generated by monocytes such as macrophages suppresses degranulation, that is, release of chemical mediators such as histamine and serotonin [J. Immunol, 159, 144
4-1450 (1997); Int. Arch.
Allergy Immunol. , 115,129
-136 (1998)] Therefore, if NO can be generated in mast cells and / or basophil cells, it is considered that allergic reaction or inflammation can be suppressed in the same manner as Ca ²⁺ channel inhibition.

In the above prior arts, it has not been clarified which molecular weight fraction among proanthocyanidins having a very wide molecular weight distribution has a strong antiallergic effect. Further, it has not been clarified by what mechanism proanthocyanidin suppresses release of inflammatory substances such as histamine and serotonin from mast cells and / or basophils.

[0008]

An object of the present invention is to provide a more effective antiallergic or antiinflammatory agent utilizing proanthocyanidin which is highly safe.

[0009]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, among proanthocyanidins having a wide molecular weight fraction, a molecular weight of 3
000 or more, more specifically molecular weight 3000 or more
It has been clarified that proanthocyanidins of 0 or less have a strong activity of inhibiting the release of chemical mediators such as histamine and serotonin described above. In addition, their proanthocyanidins are not able to convert mast cells and / or basophils into C
inhibiting the influx of Ca ²⁺ through the a ²⁺ channel and / or inducing the production of NO in mast cells and / or basophils. Histamine, serotonin, leukotriene, and other chemical mediators.

[0010] The inventor has found that if this proanthocyanidin is contained as an active ingredient, it is useful as an anti-allergic agent and an anti-inflammatory agent, and has completed the present invention based on these findings. That is, the present invention relates to a proanthocyanidin having a wide range of molecular weight fractions, of which the molecular weight is 3000 or more, more specifically, the molecular weight is 3000 or more.
It is an inhibitor of the release of inflammatory substances such as histamine and serotonin from mast cells and / or basophils of proanthocyanidins of 000 or less. Hereinafter, the present invention will be described in detail.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Proanthocyanidins, which are the subject of the present invention, can be obtained from various plant bodies, such as grape seeds, grape fruits, granberry fruits, apple fruits, red beans, cedar, pine, cypress bark, etc. from water or organic solvents. Alternatively, a concentrate of an extract containing proanthocyanidin obtained by extraction with a mixed solvent thereof, or a powder obtained by drying and powdering the concentrate and containing at least 10% or more of proanthocyanidin is preferable. In addition, the molecular weight fraction of this proanthocyanidin preparation is, from the viewpoint of its effectiveness, a molecular weight of 3000 or more, more specifically, a molecular weight of 3000 or more.
Formulations rich in the proanthocyanidin fraction of 000 or less are preferred.

[0012] Examples of such a raw material containing a large amount of the molecular weight fraction include grape fruit juice cake and seeds. Therefore, grape extract can be said to be the most economical source of proanthocyanidins and very useful as the active ingredient of the present invention. In addition, proanthocyanidins derived from grapes are rich in gallic acid esters.

As a method for obtaining a proanthocyanidin preparation containing these molecular weight fractions, purification may be performed by any method. For example, various plant materials may be purified using a mixed solvent of water and ethanol as described above. To obtain a high-purity proanthocyanidin preparation (JP-A-3-200781, JP-A-11-80148).
issue). Further, in order to further purify the proanthocyanidin preparation thus obtained and obtain a preparation containing a large amount of a proanthocyanidin fraction having a molecular weight of 3,000 or more, more specifically, 3,000 to 10,000, for example, HP2
Chromatographic method using a synthetic resin such as 0 [J. S
ci. Food Agric. , 251537-1
545 (1974)] and a solvent extraction removal method for removing unnecessary fractions with an organic solvent such as ethyl acetate (Japanese Patent Laid-Open No. 11-335).
369), a membrane separation method using a molecular weight separation membrane (Japanese Patent Publication No.
31208) and the like, a proanthocyanidin preparation having a target molecular weight fraction can be more efficiently obtained.

As such a proanthocyanidin preparation, a commercially available product may be used in addition to the preparation prepared by the above method. Examples of commercially available products containing proanthocyanidin as a main component and a large amount of a proanthocyanidin fraction having a molecular weight of 3,000 or more and 10,000 or less include, for example, "Gravinol (trademark)" and "Gravinol Super (trademark)" manufactured by Kikkoman Corporation. .

<Formulation and Administration of the Pharmaceutical Composition of the Present Invention> The form of the prophylactic / therapeutic agent of the present invention is not particularly limited. Therefore, the prophylactic / therapeutic agent may be, for example, a solution or powdery crude product / purified product derived from a plant containing proanthocyanidins. However, in order to improve the operability as a drug or the absorbability when administered to a living body, it is preferable to formulate the above proanthocyanidin in combination with an appropriate pharmaceutical carrier according to a conventional method. The prophylactic / therapeutic agent of the present invention can be administered in various dosage forms. For example, as oral administration agents, capsules, tablets, granules, fine granules, syrups,
Dry syrups and the like are exemplified. Examples of parenteral administration agents include transdermal agents such as ointments and transdermal absorbable tapes, and nasal agents such as injections, suppositories, vaginal suppositories, and sprays. The dose of the above agent to a human may be appropriately increased or decreased depending on the age, symptoms, etc. of the patient. For example, as a total of proanthocyanidins as active ingredients, usually 50 to 1000 mg, preferably 100 to 400 m per adult day.
g may be orally or parenterally administered in 1 to 3 divided doses. In addition, other anti-allergic and anti-inflammatory agents can be used in combination as the compounding raw material of the pharmaceutical composition.

<Quasi-drugs and cosmetics containing anti-allergic and anti-inflammatory agents of the present invention> Proanthocyanidins, anti-allergic and anti-inflammatory agents of the present invention, can be used by adding them to quasi-drugs and cosmetics. it can. The quasi-drugs / cosmetics to which the anti-allergic or anti-inflammatory agent is added can be used to prevent or reduce allergy and inflammation. The above quasi-drugs / cosmetics can be used in lotions, creams, emulsions, make-up products, hair products such as shampoos, soaps, household detergents, toothpastes, packs, sunscreen products, acne products, etc. it can.
It should be noted that other antiallergic and antiinflammatory agents can be used in combination as raw materials for the quasi-drugs / cosmetics.

<Food Containing Anti-Allergy and Anti-Inflammatory Agent of the Present Invention> The anti-allergic and anti-inflammatory agent of the present invention can be used by adding to foods and drinks. Further, the food or drink to which the proanthocyanidin is added can be consumed as a health food in order to prevent or reduce allergy and inflammation. In the case of producing the above foods, for example, a crudely purified or purified product of proanthocyanidin can be used as an optional food, for example, confectionery, bread, milk, various drinks, udon, buckwheat, pasta, cooked rice, seasonings, spices, prepared foods , Fats and oils-containing foods, alcoholic beverages, and soft drinks.
The food may be a powdery, tablet-type, or capsule-type food containing a crudely purified or purified proanthocyanidin as a main component and optionally containing excipients. Examples of such foods include commercially available products, for example, “Vinopower (trademark)”, “Vinoprotein (trademark)”, and “Perky Story (trademark)” manufactured by Kikkoman Corporation. In addition, other anti-allergic and anti-inflammatory agents can be used in combination as a compounding material of the food.

<Regarding Animal Feeds Containing the Antiallergic and Antiinflammatory Agents of the Present Invention> The antiallergic and antiinflammatory agents of the present invention can be used for animals other than humans, for example, mammals and birds. . In particular, prevention or treatment of anti-allergy and anti-inflammatory in domestic animals, farmed fish and pets (pets) is an important industrial issue. When the proanthocyanidins of the present invention are used for animals other than humans, they may be formulated and administered in the same manner as described above, or added to feed and fed. In addition, other anti-allergic and anti-inflammatory agents can be used in combination as a compounding material of the food.

[0019]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Reference Examples, Experimental Examples, and Examples, but the present invention is not limited to these Examples. The quantification of proanthocyanidins in Experimental Examples and Examples was determined by the following R.I. Jamb
Unathan et al. [J. Agric. Foo
d Chem. , 34, 425-429 (198
6)]. That is, the proanthocyanidin-containing sample was heated in the presence of dilute hydrochloric acid to convert proanthocyanidin into red anthocyanidin.
Measured absorbance at 0 nm; G. FIG. H. Le
a. Sci. Food Agric. ,
26, 471-477 (1978)], proanthocyanidins were quantified from a calibration curve prepared by separating and purifying from cider wine and using procyanidin tetramer as a standard. The solid content weight of the extract may be determined by lyophilizing the total amount of the proanthocyanidin-containing extract and weighing it, or after accurately measuring the total amount, extract a certain amount of extract (usually 5 m
L) and heat to dryness (usually 88 ° C.-1.5
(hr and 110 ° C.-2.0 hr), left in a desiccator for 1 hr at room temperature, weighed, and calculated in terms of total liquid volume.

Experimental Example 1 As a proanthocyanidin of the present invention, a grape seed extract containing proanthocyanidin as a main component was prepared by the following method. Using the obtained grape seed extract, the tests of Experimental Example 2 and the following were performed. First, 30% by weight of grape seeds (Vitis vinifera)
(V / v) Ethanol (80 parts by weight) was added, and the mixture was extracted for 2 weeks with occasional stirring at room temperature and filtered to obtain a crude extract. This was concentrated under reduced pressure to 1/10 volume, ethanol was added 5 times volume to the obtained concentrate, and the solution was filtered again. Then, the filtrate was concentrated under reduced pressure, and then the molecular weight fractionation membrane (molecular weight cutoff: MW = 30)
The resulting solution was freeze-dried, and the high molecular fraction and the low molecular fraction were designated GSE-H and GSE-L, respectively. GSE-L and G which are fractionated products
The molecular weight of SE-H was determined by thin-layer chromatography (FIG. 1),
Judging comprehensively from GPC analysis, NMR analysis, and mass spectrometry, GSE-L is a mixture of a molecular weight of about 300 to 3000 and GSE-L.
SE-H was presumed to be a mixture having a molecular weight of 3,000 to 10,000, and it was revealed that all fractions contained proanthocyanidin gallate. The analytical values of the obtained grape seed extract were as follows. GSE-L (flavanol content 95%, proanthocyanidin content 70%) GSE-H (flavanol content 96%, proanthocyanidin content 96%)

Experimental Example 2 Inhibition test of release of β-hexosaminidase from rat-derived basophil leukemia cells (RBL-2H3) <Test method> RBL-2H3 cells were seeded on a culture plate having 24 wells (2 × 10 4). ⁵ cell /
mL) After culturing at 37 degrees for 18 hours, anti-DNP Ig
The antibody was sensitized by adding E antibody (1 μg / mL) and incubating for 1 hour. Next, after washing three times with a PIPES buffer, a PIPES buffer containing GSE-H and GSE-L or only a PIPES buffer was added, and the mixture was incubated at 37 ° C for 10 minutes, and the antigen (DNP-HS
A, 200 ng / mL) and incubate again at 37 ° C. for 40 minutes, then lyse the cells by adding 50 μl from each well and then adding Triton, and then add 50 μg
Substrate p-hexosaminidase substrate p-
Nitrophenyl-2-acetamide-2
-0.1 M citrate buffer (pH 4.5) containing deoxy-β-glucopyranoside 20
The reaction was carried out at 37 ° C. for 60 minutes together with 0 μl. 0.2M
After stopping the reaction with a glycine buffer, the absorbance at 405 nm was measured with a microplate reader, and β-h inside and outside the cells was measured.
Exosaminidase activity was measured.

<Results> As shown in FIG. 2, β-hex from rat basophil leukemia cells (RBL-2H3)
Results of osamidase release inhibition test GSE-H
Was found to have about 10 times stronger degranulation inhibitory activity than GSE-L. This means that the release of inflammatory substances such as histamine and serotonin released by degranulation is suppressed. Therefore, the proanthocyanidins obtained in the present invention are extremely effective as antiallergic agents and antiinflammatory agents. is there.

Experimental Example 3 Inhibitory activity test of Ca ²⁺ influx through Ca ²⁺ channel using rat-derived basophil leukemia cells (RBL-2H3) <Test method> RBL-2H3 cell suspension (1 × 10 ⁶ c
cell / cell / cell) and sensitized by adding an anti-DNP IgE antibody (1 μg / mL) and incubating for 1 hour, followed by antigen stimulation (AG) to measure changes in intracellular Ca ²⁺ by a fluorescence spectrophotometer. Was measured. DNP-modified human albumin DNP-HSA (200 ng / mL) was used as an antigen, and Fura-2 AM (3 μm) was used to measure intracellular Ca ²⁺ concentration.
M) was used. <Results> As shown in FIG. 3, the increase in intracellular Ca ²⁺ concentration upon antigen stimulation (AG) was strongly inhibited by GSE-H. This indicates that the Ca ²⁺ inflow inhibitory action is mainly due to the high molecular fraction.

Experimental Example 4 Test for Inducing NO in Rat-Derived Basophil Leukemia Cells (RBL-2H3) <Test Method> RBL-2H3 cell suspension (1 × 10 ⁶ c)
ll / mL), add anti-DNP IgE antibody (1 μg / mL), incubate for 1 hour, sensitize, and add GSE-H, GSE-L, antigen (control) or buffer (blank) Then, the change in intracellular NO production during the addition was observed with a fluorescence spectrophotometer and a fluorescence microscope. <Results> As shown in FIG. 4, no intracellular NO production was observed upon antigen stimulation. Almost no intracellular NO production was observed when GSE-L was added. GSE-H
At the time of addition, clear production of NO from inside the cells was observed.

Experimental Example 5 β-hexosamine of NO
<iase release inhibition test><Testmethod> β-hexosamine was obtained in the same manner as in Experimental Example 2 using each concentration of NOR1 as the NO generator.
An idase release inhibition test was performed. <Results> As shown in FIG.
Hexosaminidase release was suppressed.

Experimental Example 6 GSE-H used in the present invention
<Acute toxicity test><Testmethod> Animals used: Commercially available F344 / DuCrj rat male and female [5 weeks old, sold by Charles River Japan Co., Ltd.] Experimental method: "Revised pharmaceutical toxicity test method guidelines G
A single dose toxicity test was conducted by the Ministry of Health and Welfare (September 1989) based on LP standards. That is, the GSE used in the present invention
-H was dissolved in distilled water for injection to obtain the dose shown in Table 1, and the specimen was forcibly administered orally once using a gastric tube.
Observation was performed for 14 days, followed by dissection.

[0027]

Table 1 Test group of single dose toxicity test of GSE-H

[0028] <Results> LD ₅₀ values of male and female rats in this test GSE-H is 2 g / kg or more (up to the limit dose:
Based on the OECD GLP guidelines (Table 2), GSE-H was determined to be safe in this test. At the necropsy on the 14th day, no microscopic abnormalities of the tissues and organs were observed, and it was judged that the toxicity was extremely low.

[0029]

TABLE 2 GSE-H single dose toxicity study of mortality and LD ₅₀

Example 1 (pharmaceutical composition: tablet for oral use) Ingredients: (1) GSE-H 60 g (2) Mannit 200 g (3) Potato starch 47 g (4) Magnesium stearate 3 g The above (1) and (2) 2), and (3) was added thereto as a 10% starch paste, and granulated. No. 60 mesh (BS) sieve. The particles were screened with a 16 mesh (BS) sieve.
After that, the mixture was mixed with a tableting machine to form tablets each having a diameter of 10 mm and a weight per tablet of 500 mg, which were used as the therapeutic agent for allergy or inflammation (oral tablet) of the present invention.

Example 2 (Quasi-drug: liquid for internal use) To 10 g of GSE-H, 1 mL of benzoic acid (45%, v / v ethanol) and purified water were added to make a total volume of 100 mL. Was used as an internal solution for prevention.

Example 3 (Cosmetic: Lotion) The following mixture ratio (% by weight) was mixed to make a total amount of 100 kg, thereby obtaining a lotion for preventing allergy or inflammation according to the present invention. GSE-H 1 Ethanol 9 Lactic acid 0.2 Citric acid 0.9 Sorbit 4 Methyl parahydroxybenzoate 0.1 Perfume Appropriate amount Purified water residue

Example 4 (Health food: capsule) 50 g of GSE-H, 50 g of potato starch, 5 lactose
0 g and 10 g of microcrystalline cellulose were mixed well, filled into capsules, and used as a capsule for preventing allergy or inflammation of the present invention containing 100 mg of the active ingredient in one capsule.

Example 5 (Animal feed: granular pet food) Pet food blending ratio (% by weight) Flour 66, soy protein 16, cheese 6, fat 3, calcium carbonate 3, fumaric acid 1, salt 2, minerals 1 , Proanthocyanidin 2 (GSE-H) After mixing with the above formulation, the mixture was granulated by a conventional method to produce a pet food for preventing allergy or inflammation of the present invention.

[0035]

The proanthocyanidins used in the present invention are among the proanthocyanidins having a wide range of molecular weight fractions, of which the molecular weight is 3000 or more, and more specifically, 300 molecular weight.
It is an inhibitor of release of inflammatory factors such as histamine and serotonin from mast cells and / or basophils of proanthocyanidins of 0 or more and 10,000 or less, and can be used as an anti-allergic and anti-inflammatory agent.

[Brief description of the drawings]

FIG. 1 is a diagram showing the results of qualitative analysis of the polymerization degree distribution of GSE-L and GSE-H. Analysis conditions Analysis conditions 100 mg / 10 mL for each sample (50% ethanol V
/ V) 4 μl (40 μg) spot silica TLC analysis (MERCK No. 1.0571)
5. 20 cm × 20 cm, silica gel 60F ₂₅₄ ) Developing solution: toluene: acetone: formic acid = 3: 6: 1 Coloring agent: MeOH 1200 mL: vanillin 48 g:
HCl 600mL

FIG. 2: β-hexos from rat-basophil leukemia cells (RBL-2H3) of GSE-L and GSE-H
It is a figure which shows the result of an aminase release suppression test.

FIG. 3 is a graph showing the results of a test on the activity of inhibiting the influx of Ca ²⁺ through Ca ²⁺ channels using GSE-L and GSE-H rat-derived basophil leukemia cells (RBL-2H3).

FIG. 4 shows the results of a NO induction test of GSE-L and GSE-H in rat-derived basophil leukemia cells (RBL-2H3).

FIG. 5 shows N using various concentrations of NOR1 as a NO generator.
It is a figure which shows the test result of (beta) -hexosaminidase release suppression of O.

Continuation of the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) A61P 29/00 A61P 29/00 37/08 37/08 43/00 111 43/00 111 113 113 113 114 114 (72) Invention Person Masatake Toyota 1-18-1 Kamioga, Setagaya-ku, Tokyo Inside the National Institute of Health Sciences (72) Inventor Shoichi Tokutake 250 Noda, Noda-shi, Chiba F-term (reference) 2B150 AA01 AA06 AA08 AA20 AB10 DD31 DD57 4B018 LB01 LB02 LB03 LB07 LB08 LB09 LE01 LE02 LE03 LE05 MD07 MD52 ME07 ME14 MF01 4C083 AC102 AC132 AC302 AC482 AC841 AC842 CC04 DD23 EE10 EE13 4C086 AA01 AA02 FA02 MA01 NA14 ZB11 ZB13 ZB11 ZB13 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZB11 ZC14

Claims (14)

[Claims] An anti-allergic or anti-inflammatory agent comprising a proanthocyanidin having a molecular weight of 3000 or more as an active ingredient. 2. The molecular weight of proanthocyanidin is 100.
2. The anti-allergic and anti-inflammatory agent according to claim 1, which is not more than 00. 3. The antiallergic or antiinflammatory agent according to claim 1, wherein the proanthocyanidin is a gallic acid ester type. 4. The anti-allergic or anti-inflammatory agent according to claim 1, wherein the proanthocyanidin is an extract obtained from juice of grape seeds, pericarp or fruits. 5. The method according to claim 1, wherein the proanthocyanidin acts as a chemical mediator release inhibitor.
5. The antiallergic or antiinflammatory agent according to 2, 3, or 4. 6. The antiallergic or antiinflammatory agent according to claim 5, wherein the chemical mediator is at least one selected from histamine, serotonin, and leukotriene. 7. The anti-allergic or anti-inflammatory agent according to claim 1, wherein the proanthocyanidin acts as an inhibitor of degranulation in mast cells or basophils. 8. The anti-allergic and anti-inflammatory agent according to claim 1, wherein the proanthocyanidin acts as an inhibitor of increase in intracellular calcium ion concentration. 9. The method according to claim 1, wherein the proanthocyanidin acts as an intracellular nitric oxide inducer.
7. The antiallergic or antiinflammatory agent according to 2, 3, 4, 5, or 6. 10. A pharmaceutical composition comprising the anti-allergic or anti-inflammatory agent according to claim 1. 11. A quasi-drug containing the anti-allergic or anti-inflammatory agent according to any one of claims 1 to 9. 12. A cosmetic containing the anti-allergic or anti-inflammatory agent according to claim 1. 13. A food containing the anti-allergic or anti-inflammatory agent according to claim 1. 14. An animal feed containing the anti-allergic or anti-inflammatory agent according to any one of claims 1 to 9.