KR102171987B1 - Composition for Anti-allergic Using Extract of Fallopia ciliinervis - Google Patents

Abstract

The present invention discloses a composition for anti-allergy using a Nadoha shou extract that exhibits degranulation inhibitory activity of mast cells when treated with the mast cell line RBL-2H3 (rat basophilic leukemia) activated with IgE and antigen (DNP-BSA).

Description

Composition for Anti-allergic Using Extract of Fallopia ciliinervis}

The present invention relates to an anti-allergic composition using an extract of Nadoha Soo ( Fallopia ciliinervis )

Allergy is a compound word created by combining Greek word'allos' meaning'changes' and'ergo' meaning'action' and has the meaning of an abnormal reaction. As the etymology suggests, allergy refers to allergen, a substance that does not show any reaction to ordinary people, causing hypersensitivity reactions such as hives, itchiness, runny nose, and cough in certain people due to innate or acquired immune function abnormalities. Typical allergens include pollen, drugs, vegetable fibers, bacteria, fungi, house dust mites, foods (egalbumin, milk protein, peanuts), hair dyes, and chemicals, and recently increased indoor life, causing allergies such as new chemicals. These allergic diseases are on the rise worldwide due to the increase in substances, environmental pollution, decrease in immune function due to stress, and changes in diet.

Allergic reactions are classified into five types: type I anaphylaxis type, type II cytolytic type, type III immune complex type, type IV cell mediated type, and type V irritant hypersensitivity reaction type, most of which belong to type I, and generally Allergic reactions are used in the same sense as type I (Roitt I, Brostoff J, Male D. Immunology 6th eds. USA. Mosby. 2001:323-383).

Representative allergic diseases include atopic dermatitis, bronchial asthma, allergic rhinitis, allergic keratitis, and skin urticaria, and mast cells are known as important acting cells in these allergic diseases (Wills-Karp M., et al., Science, 282:2258-61, 1998; Grunig G., et al., Science, 282:2261-2263, 1998). Mast cells are cells that are widely distributed in organs throughout the body, such as skin, respiratory tract, lymphatic vessels, gastrointestinal mucosa, blood vessels, and brain (Ishizaka t., et al. J. Immunol. 119:1589, 1997).

Allergic reactions are induced through activation of intracellular signaling pathways when allergens bind to IgE bound to the IgE high affinity receptor (FcεRI) on the surface of mast cells. Specifically, when allergens invade a living body, T-helper cells and B cells are sequentially activated to produce IgE. Allergens invading the living body are recognized by antigen presenting cells, and these antigen presenting cells differentiate Th0 (T helper cell type 0) into Th2 cells through the presentation of allergens. These differentiated Th2 cells secrete cytokines such as IL-4, IL-5, and IL-13, which promote the development of acidic leukocytes in the bone marrow and induce acidic leukocytes to inflamed tissues, as well as B cells. To induce the production of IgE and IgG1.

The resulting IgE binds to the high-affinity IgE receptor (FcRIα) of the mast cell membrane, and when allergens such as mites and pollen are bound to form a crosslink, the receptor (FcRIα) aggregates. Mast cells are activated by crosslinking and aggregation of receptors (FcRIα), and calcium ions (Ca ⁺⁺ ) concentration in the cytoplasm increases. The increase in calcium ion concentration acts on various intracellular regulators such as cholesterol in the cell membrane or cytoskeletal system to move the granules to the cell membrane, and at the same time, degranulation through vacuolation of the granules, fusion of granules, and fusion of granules and cell membranes. Causes. When degranulation is performed, a chemical transport material (preformed mediator) previously stored in mast cells such as histamine is released, and at the same time, newly synthesized prostaglandin, leukotriene, and the like are secreted together. In addition to histamine, serotonin and leukotriene, which have functions such as vasodilation, hypervascular permeability, contraction and secretion of bronchial smooth muscle, NCF, which acts as a chemotactic factor for inflammatory cells such as eosinophils and neutrophils. , ECF, PAF, etc., allergic reactions occur (Ennis M, et al., Br J Pharmacol 70:329-334, 1980; Metcalfe DD, et al., Crit Rev Immunol 3:23-74, 1981; Miyajima I, et al., J Clin Invest 99:901-914, 1997; Church MK, et al., J Allergy Clin Immunol 99:155-160, 1997; Jones DA, et al., J Biol Chem 268:9049- 9054, 1993).

Therefore, substances that inhibit the activation of mast cells or suppress the release of histamine can be effective treatments for allergy.

Currently, anti-histamines (alkylamines, desloratadine, etc.), mast cell stabilizers (cromoglycate, etc.), leukotriene blockers (montelukast, etc.), anti-IgE antibodies (Omalizumab), and the like are currently used as anti-allergic drugs. However, most of these drugs have temporary effects and many have severe side effects. Therefore, it can be said that there is still a need for the development of new substances that have the effect of preventing and improving allergic diseases, with little side effects and lasting effects, and in particular, natural products have the advantage of relatively low toxicity. Sewage is known to have come from China. It is a vine-like medicinal plant that has been cultivated for a long time and has been used as a folk remedy to treat inflammation, bacterial infection, and purulent dermatitis in China and Korea for a long time (Chem Pharm Bull (Tokyo). 2002. 50(5):605-) 8). In particular, Nadohasuo is understood as a closely related herbal medicine of sewage due to the similarity between the isolated anthraquinone compound and its external form, and by separating emodin, physcion and emodin-8-O-β-D-glucopyranoside from Nadohasuo. The possibility of becoming a substitute herbal medicine was suggested (Journal of the Korean Herbal Medicines Association. 1981. 12(4):221-226).

The present invention was completed by confirming that the Nadoha shou extract inhibits degranulation of mast cells in a concentration-dependent manner.

It is an object of the present invention to provide a composition for anti-allergy using Nadohasuoh extract.

Other or specific objects of the present invention will be presented below.

The present invention, as confirmed in the Examples and Experimental Examples below, inhibits degranulation when treated with the mast cell line RBL-2H3 (rat basophilic leukemia) activated with IgE and antigen (DNP-BSA). It was completed by confirming.

In consideration of the above, the present invention can be grasped as an anti-allergy composition or an antihistamine composition comprising a Nadoha shou extract as an active ingredient.

In the present specification, the term "nadohasuo extract" refers to nadohasuo stems, leaves, fruits, flowers, roots, and mixtures thereof, which are to be extracted, as lower alcohols having 1 to 4 carbon atoms such as water, methanol, ethanol, butanol, methylene chloride, and ethylene. , Acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or a mixed solvent thereof It refers to an extract obtained by leaching by leaching, an extract obtained by using a supercritical extraction solvent such as carbon dioxide, pentane, or a fraction obtained by fractionating the extract. , Heating, ultrasonic radiation, supercritical extraction, etc. can be applied. In the case of a fractionated extract, a fraction obtained by suspending the extract in a specific solvent and mixing and policing with a solvent having a different polarity, and adsorbing the extract on a column filled with silica gel, etc., and then adding a hydrophobic solvent, a hydrophilic solvent, or a mixed solvent thereof. It is meant to include the fraction obtained as a mobile phase. In addition, the meaning of the extract includes a concentrated liquid extract or a solid extract from which the extraction solvent has been removed by a method such as freeze drying, vacuum drying, hot air drying, or spray drying. Preferably, it means an extract obtained by using water, ethanol or a mixed solvent thereof as an extraction solvent, and more preferably an extract obtained by using a mixed solvent of water and ethanol as an extraction solvent.

In addition, in the present specification, the term "active ingredient" refers to an ingredient capable of exhibiting a desired activity alone or with a carrier that is not itself active.

In addition, in the present specification, "anti-allergic" is meant to include improvement (reduction of symptoms), treatment, and prevention (inhibition or delay) of allergic diseases defined below.

In addition, in the present specification, "allergic disease" refers to pathological symptoms caused by an allergic reaction mediated by the activation of mast cells, such as degranulation of mast cells, and such allergic diseases include atopic dermatitis and asthma. , Allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis, allergic keratitis, and the like.

The anti-allergic composition of the present invention may contain the active ingredient in any amount (effective amount) as long as it can exhibit the improvement activity of an allergic disease intended for treatment depending on the use, formulation, and combination purpose, etc. It will be determined within the range of 0.001% to 15% by weight, based on the total weight of the composition. Here, the term "effective amount" refers to the intended medical and pharmacological effect, such as the improvement effect of allergic diseases, when the composition of the present invention is administered to a mammal, preferably a person, to which the composition of the present invention is administered during the administration period according to the advice of a medical expert, etc. It refers to the amount of the active ingredient contained in the composition of the present invention. Such effective amounts can be determined empirically within the range of ordinary skill in the art.

In addition to the active ingredient, the anti-allergic composition of the present invention may further contain any compound or natural extract, which has already been verified for safety and known to have anti-allergic activity, in order to increase and reinforce anti-allergic activity.

Specifically, such compounds or extracts include Enterococcus faecalis heat-treated dry powder, guava leaf extract, etc., which have been individually recognized for their function of'relieving irritable immune response' in accordance with the Health Functional Foods Act, complexes such as guava leaf extract, perilla extract, lobular extract, picao preto. Compounds such as powders, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol), L. sakei Probio 65, which has been individually recognized for its function of'improving sensitive skin condition', contains gammalinolenic acid, and is derived from fruits and vegetables. Lactic acid bacteria ( L. plantarum CJLP133), probiotics ATP, and the like.

These compounds or natural extracts may be included in one or more anti-allergic compositions of the present invention ("composition of the present invention") together with the active ingredient.

The anti-allergic composition of the present invention can be grasped as a food composition in a specific aspect. When the composition of the present invention is understood as a food composition, its use can be understood as suppressing allergic skin hypersensitivity reactions.

The food composition of the present invention may be prepared in any form, such as beverages such as tea, juice, carbonated beverages, ion beverages, processed oils such as milk and yogurt, gums, rice cakes, Korean sweets, bread, snacks, and noodles. Foods, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrup, gels, jelly, can be prepared in health functional food preparations such as bars.

In addition, the food composition of the present invention can be classified as a product as long as it conforms to the enforcement regulations at the time of manufacture and distribution in terms of legal and functional classification. For example, it is a health functional food according to the Korean 「Health Functional Food Act」, or confectionery, bean, tea, and beverages according to each food type according to the food code of the Korean 「Food Sanitation Act」 (``Food Standards and Standards'' notified by the Ministry of Food and Drug Safety). , Special use food, etc.

The food composition of the present invention may contain food additives in addition to the active ingredients. Food additives can generally be understood as substances that are added to food and mixed or infiltrated in manufacturing, processing, or preserving food. Since they are consumed daily and for a long time with food, their safety must be ensured. In the Food Additive Code (“Food Sanitation Act” in Korea) governing the manufacture and distribution of food, food additives with guaranteed safety are limited in terms of ingredients or functions. In the Korean Food Additives Code (“Food Additive Standards and Standards” notified by the Ministry of Food and Drug Safety), food additives are classified into chemical synthetic products, natural additives and mixed preparations in terms of ingredients.These food additives are sweeteners and flavors in terms of function. It is divided into agent, preservative, emulsifier, acidulant, thickener, etc.

Sweeteners are used to impart a suitable sweetness to food, and both natural and synthetic can be used in the composition of the present invention. Preferably, a natural sweetener is used, and examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.

Flavoring agents can be used to improve taste or flavor, and both natural and synthetic can be used. Preferably, it is the case of using a natural one. In the case of using natural ingredients, the purpose of nutrient enhancement can be combined in addition to flavor. As a natural flavoring agent, it may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or may be obtained from green tea leaves, roundtails, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, and the like. In addition, you can use those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, and ginkgo. The natural flavoring agent may be a liquid concentrate or a solid extract. In some cases, synthetic flavoring agents may be used, and synthetic flavoring agents may include esters, alcohols, aldehydes, terpenes, and the like.

As a preservative, sodium calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. can be used, and as an emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin, etc. may be mentioned, and as the acidulant, arithmetic, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, and the like can be used. The acidulant may be added so that the food composition has an appropriate acidity for the purpose of suppressing the growth of microorganisms in addition to the purpose of enhancing taste.

As the thickening agent, a suspending agent, a settling agent, a gel-forming agent, a swelling agent, and the like may be used.

In addition to the food additives described above, the food composition of the present invention may include a physiologically active substance or minerals known in the art for the purpose of supplementing and reinforcing functionality and nutritional properties and ensuring stability as a food additive.

Examples of such physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoyl thiamine, etc., and minerals include calcium preparations such as calcium citrate, magnesium stearate. Magnesium preparations such as, iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc, and the like.

In the food composition of the present invention, the food additive as described above may be included in an appropriate amount to achieve the purpose of addition according to the product type.

With respect to other food additives that may be included in the food composition of the present invention, reference may be made to the food code of each country or the food additive code.

The composition of the present invention may be understood as a pharmaceutical composition in other specific embodiments.

The pharmaceutical composition of the present invention may be prepared in an oral dosage form or a parenteral dosage form according to an administration route by a conventional method known in the art, including a pharmaceutically acceptable carrier in addition to the active ingredient. Here, the route of administration may be any suitable route including a local route, an oral route, an intravenous route, an intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination. An example of a combination of two or more routes is a case in which two or more formulations of drugs are combined according to the route of administration, for example, when one drug is firstly administered by an intravenous route and secondly, the other drug is administered by a local route.

Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or formulation, and specifically, reference may be made to the pharmacopeias of each country, including the "Korean Pharmacopoeia."

When the pharmaceutical composition of the present invention is prepared in an oral dosage form, powders, granules, tablets, pills, dragees, capsules, solutions, gels, syrups, suspensions, wafers according to a method known in the art together with a suitable carrier It can be prepared in such a formulation. Examples of suitable carriers at this time include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, xylitol, starches such as corn starch, potato starch, wheat starch, cellulose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, Celluloses such as hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, grease Serol, etc. are mentioned. In the case of formulation, appropriate binders, lubricants, disintegrants, colorants, and diluents may be included as needed. Suitable binders include starch, magnesium aluminum silicate, starch ferryst, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweetener, sodium alginate, polyethylene glycol, wax, etc., and lubricants include oleic acid. Sodium, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, magnesium salts and calcium salts thereof, polydetylene glycol, etc., and disintegrating agents include starch, methyl cellulose , Agar, bentonite, xanthan gum, starch, alginic acid, or a sodium salt thereof. Moreover, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, etc. are mentioned as a diluent.

When the pharmaceutical composition of the present invention is prepared in a parenteral formulation, it may be formulated in the form of an injection, a transdermal administration, a nasal inhalation and a suppository according to a method known in the art together with a suitable carrier. When formulated as an injection, an aqueous isotonic solution or suspension may be used as a suitable carrier, and specifically, triethanol amine-containing PBS (phosphate buffered saline), sterile water for injection, or an isotonic solution such as 5% dextrose may be used. . When formulated into a transdermal dosage form, it can be formulated in the form of an ointment, cream, lotion, gel, external solution, pasta, liniment, air roll, and the like. Nasal inhalants can be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, and carbon dioxide, and when formulated as a suppository, the carrier is Withepsol ( witepsol), tween 61, polyethylene glycols, cacao butter, laurin paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, and the like.

Regarding the specific formulation of the pharmaceutical composition is known in the art, for example, Remington's Pharmaceutical Sciences (19th ed., 1995) and the like can be referred to. These documents are considered as part of this specification.

The preferred dosage of the pharmaceutical composition of the present invention is in the range of 0.001 mg/kg to 10 g/kg per day, preferably 0.001 mg/kg to 1 g, depending on the patient's condition, weight, sex, age, patient severity, and route of administration. May be in the /kg range. Administration can be made once a day or divided into several times. These dosages should not be construed as limiting the scope of the invention in any aspect.

The composition of the present invention may be understood as a cosmetic composition in another specific aspect. When the composition of the present invention is considered to be a cosmetic composition, its use can be understood as a use for suppressing allergic skin troubles and alleviating allergic skin irritation.

Even if the composition of the present invention is identified as a cosmetic composition, the cosmetic composition can be classified as a product for its purpose and legally, and specifically, functional cosmetics with uses such as improving skin troubles and improving atopic dermatitis, non-functional It may be general cosmetics, etc. The product form can also take any product form, specifically solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, waxes. It can take the form of a product such as a foundation or spray. In a specific product form, it may be a flexible lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, or powder formulation.

In addition to the active ingredient, the cosmetic composition of the present invention may include components commonly used in the cosmetic composition, such as stabilizers, solubilizers, surfactants, vitamins, conventional adjuvants such as pigments and perfumes, and carriers.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as a carrier component. I can.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane / May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, a solubilizing agent or an emulsifying agent may be used as a carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan, and the like may be used.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and crystallites Castle cellulose, aluminum metahydroxide, bentonite, agar, and the like can be used.

When the formulation of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters may be used.

The cosmetic composition of the present invention can be prepared according to a method for preparing a cosmetic composition commonly used in the art, except that the active ingredient exhibiting anti-allergic activity is included.

As described above, according to the present invention, it is possible to provide an anti-allergic composition using the Nadoha shou extract.

The anti-allergic composition of the present invention can be commercialized as food, cosmetics, drugs, etc. for use in improving allergic diseases.

1 is a result showing the degranulation inhibitory activity of Nadohasuoh extract in the mast cell line RBL-2H3 cells induced by inflammation.

Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these Examples and Experimental Examples.

<Example> Preparation of Nadoha Suo extract

After adding 10 times the weight of 70% ethanol to the dry powder of Nadohasuo (extraction site: outpost), leaching at room temperature for 24 hours, filtering with Whatman paper filter paper No.2, and then concentrating the filtrate under reduced pressure. Freeze-dried to prepare a solid Nadohasuo extract.

<Experimental Example> Experiment of anti-allergic activity

Rat basophilic leukemia cell line RBL-2H3 cell line in MEM medium containing 15% FBS, 100 unit/ml penicillin and streptomycin, and 2×10 ⁵ /well in a 24 well plate at 37°C and 5% CO ₂ After dispensing, it was cultured for 24 hours. After removing the supernatant, 25 ng/ml anti-DNP IgE-containing MEM medium was added and incubated for 4 hours. After incubation, wash twice with PIPES buffer (25 mM PIPES, 119 mM NaCl, 5 mM KCl, 1 mM CaCl ₂ , 0.4 mM MgCl ₂ , 40 mM NaOH, 5.6 mM glucose, 0.1% BSA) and add PIPES buffer for 10 minutes. During incubation. After incubation, the samples of the examples were treated for 20 minutes by concentration, and then DNP-BSA was added and reacted for 20 minutes. After the reaction was terminated by standing on ice for 10 minutes, the supernatant was added to a 96 well plate, 1 mM P-nitrophenyl-acetyl-β-D-glucosamined was added, and then reacted at 37° C. for 1 hour. A stop solution (0.1 M NaHCO ₃ , 0.1 M Na ₂ CO ₃ ) was added to terminate the reaction, and the absorbance was measured with an ELISA reader at a wavelength of 405 nm. As a positive control, ketotifen was used. The results are shown in FIG. 1 as a percentage compared to the sample untreated group, and the concentration IC ₅₀ value corresponding to 50% inhibitory activity was calculated and shown in Table 1 below. As a positive control, ketotifen was used.

sample IC ₅₀ (ug/ml) Nadoha Suo Extract <25 Ketotifen (positive control) 38.13

Referring to FIG. 1, it can be seen that the Nadoha shou extract inhibits degranulation in a concentration-dependent manner. Cytotoxicity was measured by the MTT method. Specifically, the remaining medium in the 96 well plate was removed, and 100 µl of serum free medium containing 10% of 5 mg/ml MTT solution was added to each well, and reacted for 2 hours by putting it in a 37°C, 5% CO ₂ incubator. After removing the medium, DMSO was added to 100 µl/well and dissolved in a shaker for 15 minutes, and the absorbance was measured at 540 nm using an ELlSA reader to determine the cell viability, and the presence or absence of toxicity of the sample was confirmed. No specific cytotoxicity was observed at the highest treatment concentration of 100 μg/ml.

Claims (6)

An anti-allergic composition comprising a mixed solvent extract of water and ethanol of Nadohasuo outpost as an active ingredient.
The method of claim 1,
The extract is an anti-allergy composition, characterized in that the 70% ethanol extract.
The method of claim 1,
The anti-allergic refers to the improvement, treatment, and inhibition or delay of the onset of allergic diseases,
The allergic diseases are atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, allergic contact dermatitis. ), and anti-allergic composition, characterized in that one selected from the group consisting of allergic keratitis.
The method according to any one of claims 1 to 3,
The composition is an anti-allergic composition, characterized in that the pharmaceutical composition.
The method according to claim 1 or 2,
The composition is an anti-allergy composition, characterized in that the food composition.
The method according to claim 1 or 2,
The composition for anti-allergy, characterized in that the composition is a cosmetic composition.

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