KR101414516B1 - Extracts of Straw for allergy treating and pharmaceutical compositions for allergy comprising the extracts - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating allergic diseases, wherein the pharmaceutical composition contains a straw extract as an active ingredient. The straw extract of the present invention decreases the production amount of allergy-causing cytokines (TNF-α, IL-4, and IL-5) and controls the production of MCP-1 and IL-6 which are inflammatory cytokines. Accordingly, the straw extract of the present invention can be usefully used as a pharmaceutical composition for preventing, alleviating, or treating various allergic diseases such as edema, hyperergia, allergic dermatitis, contact dermatitis, atopic dermatitis, skin allergies, asthma, and urticaria.

Description

TECHNICAL FIELD [0001] The present invention relates to a pharmaceutical composition for preventing or treating an allergy disease containing an extract of straw as an active ingredient,

The present invention relates to a pharmaceutical composition for preventing or treating an allergic disease containing straw extract as an active ingredient.

Allergy is an inherited or acquired disorder of the immune system. It is a sensitive reaction caused by contact with a harmless antigen, called an allergen, called an allergen. An allergen is anaphylaxis, Allergic rhinitis, asthma, atopic dermatitis, insect allergies, food allergies, drug allergies and urticaria.

The occurrence of allergies involves the interaction of various factors such as genetic factors, environmental factors, pharmacological anomalies, and immunological factors, and hypersensitivity reaction among these immune functions of the body is 4 It is classified into types of branches. The type 1 hypersensitivity reaction is caused by binding of IgE (immunoglobulin E), which is produced excessively by repeated exposure of allergen, to mast cells. As the granules containing histamine are liberated, Anaphylactic shock or focal itching and inflammation are the most common causes of atopic dermatitis (atopic dermatitis) and asthma (asthma) can be listed as. Type 2 hypersensitivity is a phenomenon in which antibodies bind to normal cells such as red blood cells, white blood cells, and platelets, causing Null (K) cells to destroy cells and cause hemopnolysis. Cyclosporin-induced hemolytic anemia Leukopenia due to aminopyrine, and thrombocytopenia due to quinidine. Type 3 hypersensitivity is a disease in which PMN (polymorphonuclear) cells damage tissues as a result of antigen-antibody complexes sticking to tissues, for example systemic lupuserythomatosis. The type 4 hypersensitivity reaction is a delayed hypersensitivity reaction. It is called contact dermatitis, which causes skin inflammation when the sensitized T cells differentiate into memory cells and then re-sensitized. Are involved in the category of contact hypersensitivity.

Atopic dermatitis is a very common disease that has a low threshold for pruritus. It is clinically diagnosed according to the age of the patient, from the infantile type characterized by skin lesions to the adult type in which the lesion is mainly formed. It shows various clinical course. In addition, patients with atopic dermatitis tend to be more susceptible to specific food or inhalation antigens than normal, have a specific vascular response to various medicines and temperatures, and resistance to infection is less resistant to specific viruses.

Atopic dermatitis is a chronic inflammatory skin disease that occurs more frequently than other allergic diseases such as asthma, allergies and allergic rhinitis. Recently, it has been estimated that the disease will occupy 10 ~ 20% of the world, and the increase of air-mediated allergen caused by air pollution, increase of exposure to antigens due to changes in residential environment (migration to cities) According to national epidemiological surveys conducted in 1995 and 2000 by the Respiratory Society, the prevalence rate of Korea is increasing from 15.3% to 17%.

Most of the atopic dermatitis is caused by immune mechanism associated with IgE (immunoglobulin E). IL-5, which induces the production of IgE from B cells, and IL-6, which secretes IL-6, which amplifies the production of IgE, from B cells. Is a Th2 cell among CD4 T cells. It has been shown that an antigen-specific T cell clone isolated from peripheral blood and skin lesions of AD patients is Th2, and cytokines such as IL-4 are secreted from these cells.

When allergens are recognized by IgE, T lymphocytes are activated by adhesion to surface IgE-adherent Fc receptors in Langerhans cells and transfer of antigen to T lymphocytes. At this time, T lymphocytes can also be activated by self-peptide or superantigen of staphylococcus aureus. In contrast to other skin diseases, inflammatory cells infiltrating into skin lesions of atopic dermatitis are mainly Th2 cells, which produce cytokines such as IL-4 and IL-5 to promote the rise of serum IgE and induce eosinophilia, The abnormal monocyte of atopic dermatitis, in which phosphodiesterase is elevated, increases the production of PGE, which inhibits the infiltration of Th1 lymphocytes. Furthermore, Th1 lymphocytes are released from splenocytes that are easily activated in atopic dermatitis TNF (tumor necrosis factor). In conclusion, atopic dermatitis inhibits Th1 proliferation and results in deterioration of cell mediated immunity. Various cytokines activate vascular endothelial cells, inducing or increasing the expression of several cell adhesion molecules, thereby promoting the return of memory T lymphocytes, thereby causing eczema lesions.

Mast cells are distributed in most organs and tissues and are important trigger cells of inflammatory reactions such as allergies and anaphylaxis. In particular, anaphylactic reactions are caused by histamine and various inflammatory cytokines released by binding IgE antigens bound to Fcε RI of mast cells. Double histamine is the most potent vascular response of immediate hypersensitivity It is a medium. Since it is also induced by compound 48/80, a synthetic compound in which histamine is liberated from mast cells, the mechanism of anaphylactic reaction has been widely used for prevention and therapeutic drug discovery as well.

Recently, urban people are increasingly exposed to various allergens such as mites in their carpets, dirt that increases with humidity, pet hair, pollen, new fruits and food as the living environment changes. As the type 1 hypersensitivity reactions, asthma and atopic dermatitis, have recently increased to become social problems, many researchers have been interested in searching for substances that can alleviate immune hypersensitivity from natural products.

For example, Korean Patent Registration No. 10-1064848 relates to a mimosa extract and a pharmaceutical composition for treating allergy comprising the same as an active ingredient, and more particularly to a mimosa extract and a mimosa extract having a mitigation and / or therapeutic effect on an allergic disease such as atopy or asthma Extract and a pharmaceutical composition for the treatment of allergy comprising the same as an active ingredient.

Korean Patent Laid-Open Publication No. 10-2012-0010984 also discloses that compound 48/80 lowers secreted histamine secreted from mast cells and inhibits allergen-induced cytokines (TNF) induced by PMA and A23187 -alpha, IL-4, and IL-8) as an active ingredient, which is effective for preventing or treating allergic diseases.

Korean Patent Registration No. 10-1064848 Korean Patent Publication No. 10-2012-0010984

The inventors of the present invention have made intensive efforts to develop a composition for preventing or treating allergic diseases derived from natural products without toxicity and side effects. As a result, the inventors of the present invention found that straw extracts inhibited allergen-induced cytokines such as TNF-a, IL-4 and IL- And the effect of inhibiting the production of MCP-1 and IL-6, respectively.

It is therefore an object of the present invention to provide a dermatological pharmaceutical composition for preventing or treating an allergic disease containing straw extract as an active ingredient.

In order to achieve the above object,

The present invention provides a pharmaceutical composition for preventing or treating an allergic disease containing straw extract as an active ingredient.

The straw extract of the present invention reduces the production of allergen-induced cytokines (TNF-a, IL-4 and IL-5) and inhibits the production of inflammatory cytokines MCP-1 and IL-6. Therefore, the straw extract of the present invention can be usefully used as a pharmaceutical composition for preventing, ameliorating or treating various allergic diseases such as edema, hypersensitivity, allergic dermatitis, contact dermatitis, atopic dermatitis, skin allergy, asthma or urticaria .

FIG. 1 is a graph showing experimental results on inhibiting TNF-a secretion of straw extract. FIG.
FIG. 2 is a graph showing experimental results on the inhibitory effect of straw extract on IL-4 secretion. FIG.
FIG. 3 is a graph showing experimental results on the inhibitory effect of straw extract on IL-5 secretion. FIG.
FIG. 4 is a graph showing experimental results on the inhibitory effect of straw extract on MCP-1 secretion. FIG.
FIG. 5 is a graph showing experimental results on the inhibitory effect of straw extract on IL-6 secretion. FIG.

The present invention provides a pharmaceutical composition for preventing or treating an allergic disease comprising straw extract as an active ingredient.

Straw refers to the stems and leaves of rice, barley, wheat, barley, etc., preferably rice straw, barley straw or straw.

The extract may be prepared by a conventional method known in the art, that is, by using a conventional solvent, such as hot water extraction, room temperature extraction, warming extraction, ultrasonic extraction, supercritical extraction and the like have.

Specifically, a solvent selected from the group consisting of water, glycols having 1 to 6 carbon atoms, anhydrous or hydrated alcohol having 1 to 4 carbon atoms, acetone, ethyl acetate, chloroform, 1,3-butylene glycol, . Preferably a mixed solvent of water and ethanol, more preferably 50 to 100% (v / v) ethanol, most preferably water, as an extraction solvent. Here, the amount of the extraction solvent used is 1 to 20 times, more preferably 5 to 10 times, the dry weight of the mixed raw material.

At this time, the extraction temperature and time may vary depending on the amount of the sample to be extracted. It is preferable that the extraction temperature and time are extracted by heating for 3 to 20 hours at 40 to 100 ° C, or for 1 to 15 days at 4 to 40 ° C. The extraction result may be subjected to filtration or purification.

In addition, the extract of the present invention can be prepared into a powder state by an additional process such as vacuum distillation, freeze-drying, or spray drying.

According to a preferred embodiment of the present invention, the allergic diseases prevented or treated with the composition of the present invention are selected from the group consisting of edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, But are not limited to, those selected from the group consisting of allergic dermatitis, atopic dermatitis, contact dermatitis, urticaria, pruritus, insect allergies, food allergies and drug allergies.

The composition of the present invention is a pharmaceutical composition for the prevention or treatment of an allergic disease containing a straw extract. When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil It is not. The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, and a preservative in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed. 1995).

The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the pharmaceutical composition can be administered by intravenous infusion, subcutaneous injection, intramuscular injection, intra-articular injection, or the like.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . Exemplary dosages of the pharmaceutical compositions of the present invention are 0.001-1000 mg / kg.

The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

As the carrier, it is possible to use purified water, monohydric alcohols (ethanol or propyl alcohol), polyhydric alcohols (glycerol, 1,3-butylene glycol or propylene glycol), higher fatty acids (palmitic acid or linolenic acid) But are not limited to, camellia oil, jojoba oil, olive oil, squalane, sunflower oil, macadamia peanut oil, avocado oil, soybean water added lecithin or fatty acid glyceride). If necessary, a surfactant, a bactericide, an antioxidant, an ultraviolet absorber, an anti-inflammatory agent and a refreshing agent may be added.

Surfactants may be selected from the group consisting of polyoxyethylene, hardened castor oil, polyoxyethylene, oleyl ether, polyoxyethylene monooleate, polyoxyethylene, glyceryl monostearate, monostearic acid sorbitan, monooleic acid polyoxyethylene, sorbitan, Fatty acid esters, hexaglycerol monolaurate, polyoxyethylene reduced lanolin, POE, glyceryl pyroglutamic acid, isostearic acid, diesters, N-acetylglutamine and isostearyl esters.

The bactericide may optionally comprise a group consisting of hynochytol, trichloro acid, chlorohexidine gluconate, phenoxyethanol, resorcin, isopropylmethyl phenol, azulene, salicylic acid and zinc pyrithione .

As the antioxidant, any of butylhydroxy anisole, gallic acid, propyl gallate, and erosorbic acid can be used.

Ultraviolet absorbers include benzophenones such as dihydroxybenzophenone, melanin, ethyl p-aminobenzoate, 2-ethylhexyl paradimethylaminobenzoate, synoxothiom, 2-ethylhexyl phamethoxycinnamate, 2- (2-hydroxy -5-methylphenyl) benzotriazole, urocanic acid and metal oxide fine particles.

As the anti-inflammatory agent, dipotassium glycyrrhizinate or allantoin can be used, and as a refreshing agent, pepper tincture or 1-menthol can be used.

Hereinafter, preferred embodiments and experimental examples are provided to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

Example 1: Production of rice straw extract

100 g of rice straw was finely pulverized and then immersed in 1 L of water for 72 hours. The precipitate was filtered, and the filtrate was concentrated using a vacuum distiller, and then dried in a freeze dryer.

Experimental Example 1: Anti-inflammatory and allergic experiments using Jurkat cells

1-1. Experimental Method

Cells were inoculated into a 24-well plate at 1 × 10 ⁶ cells (0.5% FBS-RPMI medium) for 1 hour at 37 ° C. After one hour, 10 μg / ml of house dust mite powder was added and cultured. After 6 hours, The extracts were incubated with 0.1 ug / ml, 1 ug / ml and 10 ug / ml for 16 hours. After incubation, the supernatant was taken and the inflammatory and allergic cytokines TNF-a, IL-4 and IL-5 were measured by ELISA kit.

1-2. TNF-a production in Jurkat cell line

The results of measuring the effect of rice straw extract on TNF-a production in Jurkat cell line are shown in FIG. 1 and Table 1 below.

Experimental group TNF-a production (pg / ml) division Normal group ± 2.9 Jurkat cell culture medium Control group 8 ± 1.9 Jurkat cell line + house dust mite Experiment 1 ± 1.5 Jurkat cell line + house dust mite + straw extract (0.1 ug / ml) Experiment 2 ± 1.6 Jurkat cell line + house dust mite + straw extract (1 ug / ml) Experiment group 3 ± 1.4 Jurkat cell line + house dust mite + straw extract (10 ug / ml)

As a result of measuring the amount of TNF-a produced, it was confirmed that the rice straw extract inhibited the secretion of TNF-a as shown in Table 1 and FIG. 1

1-3. IL-4 production in Jurkat cell line

The results of measuring the effect of straw extract on IL-4 production in Jurkat cell line are shown in FIG. 2 and Table 2 below.

Experimental group IL-4 production amount (pg / ml) Normal group 77 ± 2.8 Control group 327 ± 15.9 Experiment 1 71 ± 20.3 Experiment 2 50 ± 6.8 Experiment group 3 21 ± 7.8

As a result of measurement of the amount of IL-4 production, as shown in Table 2 and FIG. 2, it was confirmed that the rice straw extract inhibited the secretion of IL-4.

1-4. IL-5 production in Jurkat cell line

The results of measuring the effect of straw extract on IL-5 production in Jurkat cell line are shown in FIG. 3 and Table 3 below.

Experimental group IL-5 production (pg / ml) Normal group 77 ± 2.8 Control group 327 ± 15.9 Experiment 1 71 ± 20.3 Experiment 2 50 ± 6.8 Experiment group 3 21 ± 7.8

As shown in Table 3 and FIG. 3, it was confirmed that the rice straw extract inhibited the secretion of IL-5.

Experimental Example 2: Anti-inflammatory and allergic experiments using EoL cells

2-1. Experiment

Cells were plated in a 24-well plate at 1 × 10 ⁶ cells / well (0.5% FBS-RPMI medium) for 1 hour at 37 ° C. After one hour, 10 μg / ml of house dust mite powder was added and cultured for 24 hours Straw extracts were added at a concentration of 0.1 ug / ml, 1 ug / ml and 10 ug / ml for 6 hours. After the incubation, the supernatant was taken and the inflammatory and allergic cytokines, MCP-1 and IL-6, were measured using an ELISA kit.

2-2. The amount of MCP-1 produced in the Eol cell line

The results of measuring the effect of straw extract on the amount of MCP-1 produced in the Eol cell line are shown in FIG. 4 and Table 4 below.

Experimental group Production of MCP-1 (pg / ml) division Normal group 39 ± 6.4 Eol cell culture medium Control group 96 ± 2.4 Eol cell line + house dust mite Experiment 1 46 ± 3.5 Eol cell line + house dust mite + straw extract (0.1 ug / ml) Experiment 2 58 ± 10.2 Eol cell line + house dust mite + straw extract (1 ug / ml) Experiment group 3 12 ± 0.2 Eol cell line + house dust mite + straw extract (10 ug / ml)

As shown in Table 4 and FIG. 4, it was confirmed that the rice straw extract inhibited the secretion of MCP-1.

2-3. IL-6 production in Eol cell line

The results of measuring the effect of straw extract on IL-6 production in Eol cell line are shown in FIG. 5 and Table 5 below.

Experimental group IL-6 production (pg / ml) division Normal group 94 ± 4.2 Eol cell culture medium Control group 163 ± 10.6 Eol cell line + house dust mite Experiment 1 133 ± 12.7 Eol cell line + house dust mite + straw extract (0.1 ug / ml) Experiment 2 80 ± 14.1 Eol cell line + house dust mite + straw extract (1 ug / ml) Experiment group 3 72 ± 9.9 Eol cell line + house dust mite + straw extract (10 ug / ml)

As shown in Table 5 and FIG. 5, it was confirmed that the rice straw extract inhibited the secretion of IL-6.

Claims (3)

A pharmaceutical composition for preventing or treating an allergic disease containing straw extract as an active ingredient. The method according to claim 1, wherein the allergic disease is selected from the group consisting of edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, atopic dermatitis atopic dermatitis, contact dermatitis, urticaria, pruritus, insect allergies, food allergies and drug allergies. The pharmaceutical composition for preventing or treating allergic diseases according to claim 1, wherein the straw is straw straw, barley straw or dense straw.

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