KR20110087149A - Functional food composition and pharmaceutical composition for the prevention and alleviation of allergy symptoms - Google Patents

Abstract

PURPOSE: Functional food and pharmaceutica compositions for preventing the allergic symptoms are provided to offer the treatment effect on allergic diseases to users with allergic rhinitis, asthma, or atopic dermatitis. CONSTITUTION: Functional food and pharmaceutica compositions are produced by the following steps: mixing glycyrrhizae radix, curcuma longa, green tea leaves, taraxacum platycarpum, perilla frutescens, fermented soybeans, trigonella foenum-graecum, scutellaria baicalensis, and black pepper powder; and extracting the mixture using microwaves after adding purified water and an alcohol water solution.

Description

FUNCTIONAL FOOD COMPOSITION AND PHARMACEUTICAL COMPOSITION FOR THE PREVENTION AND ALLEVIATION OF ALLERGY SYMPTOMS}

The present invention is 2-10 parts by weight of licorice, 2-10 parts by weight of turmeric, 10-30 parts by weight of green tea, 10-30 parts by weight of dandelion, 5-20 parts by weight of perilla, 2-10 parts by weight of cheonggukjang, Food composition for the prevention and improvement of allergies containing 10-30 parts by weight fenugreek, 10-30 parts by weight of gold, and 1-5 parts by weight of pepper as an active ingredient, a beverage containing 1-15% by weight of the active ingredient And pharmaceutical compositions for the prevention and treatment of allergies.

In recent years, allergies are increasing day by day due to changes in eating habits and pollution, and 20-25% of people have symptoms of atopic dermatitis (AD), asthma and rhinitis. This causes serious social problems by drastically reducing the quality of life. Food allergy is identified in 6-8% of infants, and AD in children is 35% due to food allergy and can never be ignored.

Allergic diseases include asthma, allergic dermatitis, atopic dermatitis, allergic conjunctivitis, allergic enteritis, etc. The most common ones are asthma and allergic rhinitis and respiratory disorders and atopic dermatitis.

Asthma is a chronic inflammatory disease caused by representative inflammatory cells such as mast cells and various humoral inflammatory mediators such as eosinophils and T-lymphocytes, and is characterized by reversible airway obstruction and bronchial hypersensitivity. The substance is involved. Substances involved in asthma include interleukin, an inflammatory cytokine other than leukotriene C4, D4, and E4, a metabolite of 5-lipoxygenase known as the slow reacting substance of anaphylaxis (SRS-A). Interleukin, IL) -4, -5 and -6 are known to be involved.

Bronchial asthma is also a disease of inflammatory reactions. Inflammation is a defense of biological tissues against local body injuries. In other words, in response to various harmful stressors, the biodefense reaction to remove the injury caused by the stimulus and restore the original state is an inflammatory response. Stimulation of inflammation includes infection, chemical and physical stimuli, and bio-constitutive factors related to the inflammatory response include low-molecular or polymer chemicals such as free radicals, proteins, sugars, and lipids, plasma, blood cells, and blood vessels. And connective tissue. The process of inflammation can be divided into two types: acute inflammation and chronic inflammation. Acute inflammation is a short-term reaction within days, chronic inflammation has a long duration, and tissue proliferation is shown.

Allergic rhinitis is a hypersensitivity reaction to a specific substance in the nasal mucosa. After allergens (antigens) have been exposed to the nasal mucosa, they stimulate the nasal mucosa to mediate various types of IgE antibodies, including erythrocytes and eosinophils. Inflammatory cells are caused by the inflammatory reactions caused by the various mediators secreted by them. It is characterized by three main symptoms: seizure sneezing in a row, clear runny nose, and stuffy nose. In addition to the characteristic symptoms, it may be accompanied by itching around the nose, headache, and olfactory deterioration. Complications may include otitis media, sinusitis, and pharyngitis.

Allergic rhinitis is classified into intermittent allergic rhinitis, which occurs only in a short period of time depending on the duration of symptoms, and persistent allergic rhinitis, which occurs over a month or more, and is mild and moderate depending on the severity of symptoms. Moderate Severe. It is also divided into seasonality, which occurs only in one particular season, and perennial seizures throughout the year. Seasonal allergic rhinitis is often associated with the season in which pollen is flying, but it is chronic, continues throughout the year, and occurs seasonally regardless of season.

Allergic rhinitis is a typical allergic disease caused by the combination of genetic and environmental factors along with allergic asthma. Typical exacerbations of rhinitis include climate change, colds, air pollution and stress.

Atopic dermatitis is a chronic, recurrent inflammatory skin disease that usually begins in infancy or childhood, accompanied by pruritus (itch), dry skin, and characteristic eczema. In infancy, it begins with eczema on the stretched side of the face and limbs, but as it grows, it is characteristic of eczema in the flexion of the arms and behind the knee, and in many cases it tends to improve naturally as it grows. . In adults, the skin becomes thicker in lichenification when the skin is folded, and eczema is more common on the face than in infants. Atopic dermatitis is on the rise worldwide, with a prevalence rate of 20% of the population.

The cause of atopic dermatitis is not yet known. Because clinical symptoms also appear in various cases such as dry skin and eczema, the cause of the disease cannot be explained by any one, but environmental factors, genetic predisposition, immunological reactions and abnormal skin barriers are considered to be the main causes. Environmental factors include environmental pollution such as soot from industrialization, increased use of food additives, increased use of carpets, beds and sofas due to Western-style dwellings, house dust and mites caused by increased room temperature. (Allergen) increases.

Allergic diseases are mediated by IgE, which is known to play an important role in this process by type 2 T helper (Th2) cells, mast cells and acidic leukocytes (eosinophil). IgE is one of many immunoglobulin isotypes commonly present in the serum of human or some other animal species, without helminth infection or other stimuli. IgE is likely to be produced in immunological conditions predominantly humoral immunity mediated by cytokines such as Th2 cells, IL-4, IL-5 and IL-13. The current concept of the pathogenesis of allergic diseases suggests that genetic and environmental factors interact with each other, thereby producing IL-4 via Stat6-mediated signaling pathways and c-Maf, GATA3, NIP45 and Activation of specific transcription factors such as NFATc and consequently leads to the development of allergen-specific T helper 2CD4 + cells. Th2 cells activated by allergens once produced secrete IL-4, IL-5 and IL-13. IL-4 and IL-5 induce the production of IgE and IgG1 by B cells, stimulate the development of acidic leukocytes in the bone marrow and induce them to collect in inflamed tissue. IL-13 is a cytokine closely related to IL-4, which binds to the IL-4 receptor alpha chain and induces an allergic phenotype regardless of IL-4, IgE or acidic leukocytes. IgE also circulates and binds to the IgE receptors of two isoforms. Affinity IgE receptors (FcεRI) are present on the surface of mast cells and basic leukocytes, and low affinity IgE receptors (FcεRII or CD23) are present on the surface of lymphocytes, acidic leukocytes, platelets and macrophages. The most important factor governing the pathogenesis of allergic diseases is believed to be the cross-linking of IgE receptors on mast cells and the resulting degranulation of mast cells after encountering allergens. Molecules released by mast cells include histamine, heparin, proteases and free radicals and mediate various biological effects such as vasodilation, intestinal and / or bronchial smooth muscle contraction, mucus secretion and local protein secretion. Influx of leukocytes, basic leukocytes and lymphocytes occurs after 6-24 hours following the initial mediated response of mast cells. This late stage response leads to chronic inflammation of tissues constantly exposed to the antigen. Generally, for the prevention of allergic diseases, compositions such as antihistamine, steroidal or nonsteroidal anti-inflammatory drugs and leukotriene antagonists are used. Such compositions are primarily useful for symptomatic effects and do not provide the protection required for the fundamental healing of allergic diseases such as alleviating excessive humoral immunity or inhibiting IgE production.

Food allergy is an immune hypersensitivity reaction caused by food through the digestive tract, and reported to be associated with type I, type III, and type IV, and type I is one of the typical reactions. Type I immediate hypersensitivity reactions are divided into two stages. In the first stage, the immune response is balanced by invasion of allergens, and IL-4 and IL-13 are secreted due to excessive immune responses of Th2 cells. IgE-specific antibodies produced by the cells are attached to the surface of mast cells or basophils to prepare for allergic development. It is said to be sensitized to allergens. Here, the helper T cells include Th1 cells including IL-12 and IFN r and Th2 cells such as IL-4, IL-5 and IL-13. Excessive secretion of IL-4 by Th2 cells contributes to allergic reactions by increasing IgE production, IL-12 and IFN r produced by Th1 cells inhibit the secretion of IgE and IgG1 and increase the secretion of IgG2a .

The second stage of allergic development is divided into early and late reactions. The initial reaction involves allergens reinvading the body, stimulating mast cells, and vasodilation caused by histamine, lipid metabolites, and cytokines released from the cells. In the late reaction, neutrophils, eosinophils, macrophages, Th2 cells, basophils, and the like are activated by infiltration, causing atopic dermatitis, rhinitis, and asthma. Among such degranulated secretion substances, histamine is the most well known factor and is used as an important indicator of allergic symptoms in connection with immediate type hypersensitivity reactions.

In the case of allergic patients, food allergens penetrate into the undigested state through the intestine, and the intestinal absorption of allergens is the first step in the development of food allergy. The secretary is not only the organ responsible for digestion and absorption of nutrients, but is also involved in various bioregulations. Intestinal epithelial cells not only have major functions such as digestive absorption, barrier, and expression / transmission / transformation, but also underestimate the role of the gut / intestinal tract, such as the development of a unique mucosal immunity or nervous system. Can't.

Intestinal epithelial cells limit the penetration of macromolecules by a tight junction as a barrier, but may increase food permeability when the barrier is destroyed. In general, ingested proteins are hydrolyzed and absorbed by digestive enzymes in the intestinal tract, but in the intestinal dysfunction of the digestive tract and intestinal status, or in the immature intestine of young children, some proteins are intact in the form of a barrier. Pass through. These act as allergens and cause allergic reactions in some people. Intestinal diseases such as intestinal disease, celiac disease, food allergy, and acute pancreatitis, which are associated with increased intestinal epithelial permeability, can cause intestinal barrier dysfunction due to damage of tight junctions of epithelial cells. In other words, enhancing the function of the intestinal barrier through stabilization of tight junctions will prevent food allergies.

Therefore, to prevent such allergies, three ways can be considered. In other words, the control of the first stage reaction of allergy onset through Th1 / Th2 cytokine balance control and the control of the second stage on the basis of degranulation inhibition, and finally, allergen, the prerequisite for allergy onset of food allergens, by inhibiting the passage of food allergens into the intestinal epithelial layer. Can control the absorption of the body.

Type I IgE mediated allergic inhibitory activity has been reported in food and natural products. According etc. Park Quercetin is through the Th1 / Th2 immune response regulation in the asthma-induced mice system induced by OVA were reported to suppress the allergic reaction (Park HJ et al. Quercetin regulates Th1 / Th2 balance in a murine model of asthma. Int Immunopharmacol 9: 261-7, 2009). In addition, it has been reported that the saccharides of garlic, perilla oil, konjac, polysaccharides of leafy veins, polysaccharides of Ganoderma lucidum mushroom, polysaccharides of Japanese soy sauce, royal jelly, and Cordyceps sinensis also inhibit allergic reactions with this activity.

In addition, it has been reported that food allergens inhibit the passage of food allergens by stabilizing intestinal epithelial cells by peptides and cell wall components (Isobe N, Suzuki et al. ... Induced Intestinal Inflammation Biosci Biotechnol Biochem 72:. 1740-1745, 2007).

As such, food and plant-derived natural products have been used as herbal and folk remedies for the treatment and prevention of various diseases including allergies in Korea and the East.

In general, the prevention and treatment of allergies induces an allergen-induced immune response from Th2 to Th1 to produce IgG instead of IgE through hyposensitization, in which allergens are gradually administered from low concentrations, or differentiate Th0 cells into Th1 cells. To reduce the production of IgE by administering IFN-γ, IL-10, IL-12, TGF-β, or Th1-stimulated adjuvant.

Currently, antiallergic drugs are mainstream as drugs, and second and third generation antihistamines are mainly sold. Existing anti-allergic drugs are mostly coping therapies that alleviate allergic symptoms, and many drugs act on the inflammatory system, and even now, new drug development has many drugs related to new chemical delivery agents in inflammation. In recent years, the development of drugs that act on the immune system has been increasing, specifically, allergic reactions such as cytokine, IgE antibodies, T cell / B cell function regulation, cell adhesion process, and intracellular information transfer control. Many attempts have been made to develop fundamental therapeutic drugs aimed at suppressing the onset.

However, there is no satisfactory composition that can effectively control allergy by acting at each stage causing allergic symptoms such as allergen small intestinal epithelial cell passage, Th1 / Th2 immune response, and degranulation. It is urgent to provide an effective anti-allergic composition for patients suffering from allergic diseases that are increasing day by day due to air pollution and environmental pollution that are worsening year by year, and food allergic patients increasing year by year.

The problem to be solved by the present invention is to provide a food composition for the prevention and improvement of allergic diseases for allergic patients.

Another object of the present invention is to provide a beverage for the prevention and improvement of allergic diseases.

Another object of the present invention is to provide a composition for the prevention and improvement of food allergic diseases.

Another object of the present invention is to provide a pharmaceutical composition for the prevention and treatment of food allergic diseases.

In order to achieve the above object, the present invention provides a composition for the prevention, treatment and improvement of allergic diseases containing the extract of licorice, turmeric, green tea, dandelion, perilla, cheonggukjang, fenugreek, golden, and pepper as an active ingredient. do.

For the development of the composition as described above, the inventors of the present invention were selected based on the food material, non-toxic, each step of allergy-induced with respect to the above nine materials, except that it is not available as a food noticed by the KFDA Through small intestinal epithelial cells passing through, Th1 / Th2, and degranulation experiments to confirm that all have the efficacy, and the appropriate ratio of the combination of these materials confirmed the ratio that shows the most effective results of the present invention was completed. .

The ratio of the functional composition exhibiting efficacy in the allergy of the present invention is 2-10 parts by weight of licorice, 2-10 parts by weight of turmeric, 10-30 parts by weight of green tea, 10-30 parts by weight of dandelion, 5-20 parts of perilla It consists of parts by weight, 2-10 parts by weight Cheonggukjang, 10-30 parts by weight fenugreek, 10-30 parts by weight golden, and 1-5 parts by weight pepper. By appropriately adjusting the blending ratio according to the characteristics of the food composition, beverage, and pharmaceutical composition can enjoy the maximum anti-allergic effect.

Licorice ( Glycyrrhiza) used in the present invention uralensis includes European licorice (Glycyrrhizaglabra), Manchurian licorice (G.uralensis), and spear and licorice (G.inflata), a genus of licorice (Glycyrrhiza ) of the legume (Leguminosae). Licorice is

Food that has been ingested for centuries and has been used as a food additive and a herbal medicine.

Curcuma used in the present invention Turmeric, the raw material of aromatica ) extract, is the root or root stem of turmeric, a perennial herb in the curcuma of ginger family. Turmeric is a food that has been ingested for centuries as a "turmeric" spice, and the turmeric pigment obtainable by extracting turmeric with an organic solvent such as ethanol, hexane or acetone has been approved for use as a food additive for coloring and is safe. high.

Green Tea is Thea Dried leaves of sinensis L.). The main ingredient is catechins. Blood pressure lowering action (Hara. Y et al., Nippon Nogeikagaku Kaishi, 61, pp803, 1987), antioxidant activity (Matsuzaki, T et al., Nippon Nogeikagaku Kaishi, 59, pp129, 1985) on these catechins Various physiological activities, such as preventive action and caries prevention action, have been reported. Among the catechins, (-)-epigallocatechin gallate ((-)-Epigallocatechingallate) is the most representative bioactive substance.

Dandelion ( Taraxacum platycarpum ) is distributed in Korea, China and Japan, and grows in sunny places in the field. Stems are absent, leaves aggregate from roots and spread laterally. Leaves are upside down bassos, 6-15cm long, 1.2-5cm wide, deeply dug-shaped, with serrated edges and some hairs. In oriental medicine, plants before flowering are used as a medicine called pogongyoung (蒲公英), which is effective for swelling, mastitis, sore throat, appendicitis, peritonitis, acute hepatitis, and jaundice due to heat, and is also used for symptoms of urinating due to fever. In the private sector, it is also used as a drug for quick secretion of milk.

Perilla frutescens var . acuta ) is also known as Jaso or lobule, and is native to China. Stems stand straight, 20-80 cm high, rectangular in cross section, purple, with scent. The leaves are opposite, broad egg-shaped, pointed at the end, rounded at the bottom, and serrated at the edges. Hair on both sides of leaf, long hair on back vein, long petiole. In oriental medicine, the leaves are called lobules and seeds are called Jajaja (紫蘇 子). When you eat fish or crabs and have food poisoning, drink the juice from the leaves or boil the leaves.

Cheonggukjang is one of Korea's representative fermented foods made from soybean. It is one of the traditional types of soy sauce, soy sauce, soybean paste, and red pepper paste that have been commonly used to this day. The state has played an important role as a food. Cheonggukjang is made by using Bacillus subtilis called Bacillus subtilis, which is attached to rice straw, and gives its unique taste and smell by enzymes produced by Bacillus subtilis during fermentation. In addition, it produces a large amount of viscous substance, which is a mixture of levan form fructan and polyglutamate derived from sugar and protein of raw soybeans. High quality soybean fermented food with high protein and fat content.

Fenugreek (胡蘆 巴, Trignonellae foenum - graecum L.) is an annual herb that belongs to the legumes and uses mature seeds for medicinal purposes. According to the agreement, fenugreek is warm, so the genitals are weak and cold, so that the lower abdomen and flanks are pale, and around the eyes or the face is dark. Fenugreek is born with spring and summer nourishment, enters the genitals, reinforces the kidneys, improves the vitality, enters the liver, and becomes a potion to treat cold and moist energy, and when taken long, promotes libido, helps the stomach, and prolongs life. Fenugreek is a nourishment tonic in clinical use, not only for kidney disease, swelling and pain in the testicles, sexual neurasthenia, erectile dysfunction, ferocious cold, but also for bladder pain, sudden stomach pain, abdominal pain, weak legs, and foot disease. do.

Golden ( Scutellaria baicalensis ) belongs to Lamiaceae and is native to northern China in East Asia, and is found in mountainous regions of Korea, and is distributed in East Siberia, Mongolia, China, and Manchuria. Brought in medicinal plants,

Cultivated naturalized plants, often grown in fields. Breeds as roots or seeds. In the herbal medicine, golden is dried roots. In spring or autumn, the roots are dug up, scrape off the husks and rotten genus, rinse in water, dry in the sun, and use it as a medicinal herb. The root is yellow so it is called golden.

Pepper (Piper nigrum L.) is a highly irritating, aromatic plant that is native to India, and is also cultivated in East and West India, Brazil, the United States, Taiwan, Indonesia, Malaysia, and China. The amount of irritant contained in the fruit is about 6 to 13% and the amount of pepper essential oil is about 2 to 3%. Pepper berries have been used to prescribe cholera, indigestion, diarrhea, various gastrointestinal diseases, stroke and arthritis. Species belonging to the genus Piper genus have been widely used for the treatment of perfumes, stomach, teeth and other diseases.

Extracts of the components used in the present invention can be obtained by extracting the active ingredient of the ingredient with an organic solvent. Preferably, as the organic solvent, lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, and butanol are used. Preferably 30-80% ethanol is used. The highest amount of active ingredient can be obtained in the above range. Another extraction method involves first extracting the hydrophilic component with water or an alkaline aqueous solution and then extracting the residue as it is or after drying with an organic solvent. The organic solvents used in this process are preferably applied for use in the production and processing of pharmaceuticals, foods, and food additives, including acetone, ethanol, glycerol, ethyl acetate, diethyl ether, cyclohexane, butanol, propanol, Propylene glycol, hexane, methanol and the like. Cold extraction can be used, and oils such as edible oils can also be used. Mixtures of two or more of these solvents and mixtures of these optional solvents with water can also be used. In addition, ethyl acetate, acetone or ethanol are preferred for extracting the fractions of these components with good efficiency using a single solvent. Extracts of the above components may be obtained by selecting each component and washing with water, cutting off water, or adding an aqueous solution of alcohol or 50-60 times by weight of each component to extract for 1-10 hours at 50-150 ° C. Below 50 ° C., the extraction of the active ingredient is not sufficient, and above 150 ° C., the active ingredient may be modified. The extract is defined herein as an extract obtained by extracting the hydrophobic fraction or an extract from which the extraction solvent is removed. Methods of extracting active ingredients are well known to those skilled in the art.

In the embodiment of the present invention, the extract of each component was obtained using a microwave much shorter than the above extraction methods. Extraction method is to wash raw materials such as dry natural materials, washed with water and cut into 1-2cm, 10-30 times the weight ratio of purified water or alcohol aqueous solution by using the microwave (60 ~ 120W) for 2-30 minutes Obtained by extraction

The anti-allergic food composition according to the present invention can be prepared in the form of a high concentrate or powder form. After mixing the extract, 5-10 times of water is added and concentrated by heating to 70 ℃ ~ 100 ℃, or by drying the concentrate to prepare a powder of 50 ~ 150 mesh (mesh). In addition, the anti-allergic food composition of the present invention is prepared by mixing the above ingredients and steamed with steam at 20 to 30 minutes at 100 ℃ and dried in a dryer for 1 to 2 hours at a temperature of 40 to 50 ℃, then powdered It may be, but the manufacturing method is not limited to these.

The food composition can be used for food additives or beverages. When used as a food additive, as known to those skilled in the art, it can be prepared in powder form or slurry form by containing, without limitation, calcium carbonate, calcium phosphate, pyroic acid and gum arabic. Food additives can be added to gums, candies, sweets, vitamin complexes and the like. Drinks may be prepared by mixing 600 to 900 parts by weight of water to 100 to 300 parts by weight of the food composition prepared above, stirring and pasteurizing at 60 to 65 ° C. for 30 minutes to 1 hour, at which time flavor Sugar, sugars, and spices commonly used for the purpose of addition may be added according to the consumer's preference. Any food carrier that can be used in the present invention may be appropriately selected depending on tablets, pills, granules, capsules or powders as long as they are known in the art. Specific examples include lactose, starch, magnesium stearate, talc and the like. Food additives and beverages of the present invention can be prepared as a functional beverage by mixing in water so as to include 1-15% by weight based on the total weight of the food, by drying and powdering the ingredients used in the preparation of capsules, tablets, granules, etc. Can be. If you use less than 1% by weight, allergic inhibitory activity is weak, if you use more than 15% by weight can feel the rejection due to the flavor of the drug.

In the beverage composition of the present invention, a natural flavoring agent composed of, for example, taumartin, stevia extract, etc., which is used in preparing a general beverage, for example, a synthetic flavor selected from saccharin and aspartame, and / or monosaccharides, di Natural carbohydrates selected from saccharides, oligosaccharides, and polysaccharides can be added.

The present invention provides an anti-allergic pharmaceutical composition comprising a pharmaceutically acceptable carrier and the composition in a pharmaceutically effective amount. The present invention provides a method of treating an individual comprising administering the composition to an individual suffering from an allergic disease.

As pharmaceutical preparations, the pharmaceutical compositions of the invention are generally administered in the form of pharmaceutical compositions comprising the active composition of the invention and comprising a pharmaceutically acceptable carrier or carrier suitable for use in pharmaceutical preparations. The amount of the composition administered will usually be determined by the physician taking into account relevant circumstances, including the subject disease, the route of administration chosen, the composition actually administered, age, weight and individual patient's response, the severity of symptoms, and the like. Dosages range from 10 mg to 500 mg once or several times daily.

The pharmaceutical compositions of the invention can be administered by a variety of routes including oral, rectal, transdermal, subcutaneous, intravenous, intramuscular and nasal. The pharmaceutical composition of the present invention is preferably formulated in one of the injectable or oral compositions depending on the intended route of delivery.

Compositions for oral administration may take the form of bulk liquid dilutions or suspensions, or bulk powders. More generally, it is provided in unit dosage form to facilitate accurate dosing. The term "unit dosage forms" refers to completely separate units suitable for one dose to be administered to patients and other mammals, each of which is calculated and determined in advance to produce the desired therapeutic effect. Amounts of the active substance are in combined form with appropriate pharmaceutical excipients. Common unit dosage forms include ampules or syringes in which the liquid composition is prefilled and measured, or in the case of solid compositions, pills, tablets, capsules and the like. Liquid forms suitable for oral administration may include suitable aqueous or non-aqueous carriers with buffers, suspensions and dispersants, colorants, spices, and the like. Solid preparations may include, for example, the following components or compounds of similar nature: binders such as microcrystalline cellulose, gum tragacanth or gelatin; Excipients such as starch or lactose; Disintegrating agents such as alginic acid, Primogel or corn starch; Lubricants such as magnesium stearate; Glidants, such as colloidal silicon dioxide; Sweeteners such as sucrose or saccharin; Or a flavoring agent such as mint, methyl salicylate or orange flavoring.

Injectable compositions are generally based on sterile saline for injection or phosphate-buffered saline (PBS) or other injectable carriers known in the art. As above, such compositions of the present invention usually comprise from about 0.05 to 10% of the combined weight of the residue, such as an injectable carrier. The above ingredients for oral or injectable compositions are only representative. Other materials and treatment methods and the like are disclosed in Remington's Pharmaceutical Sciences (Part 8 of Remington's Pharmaceutical Sciences, 17th edition, 1985, Mack Publishing Company, Easton, Pa.).

The compositions of the present invention may also be administered in a sustained release form or a sustained release drug delivery system. Representative sustained release materials are described in the Remingtons Pharmaceutical Sciences Additives column.

In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

Each of the components of the composition according to the present invention was excavated from the material declared to be usable as a food by the KFDA, so no toxicity and other side effects were found.

The present invention provides a composition having the effect of preventing, ameliorating, and treating allergic diseases to patients with allergic diseases such as asthma, allergic rhinitis or atopic dermatitis. This can have the effect of contributing to the promotion of useful agricultural products that are active in the prevention, improvement and treatment of allergies and contributing to the increase of farm income.

Hereinafter, the specific method of the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited only to these Examples.

Example  1: Extraction of Anti-allergic Composition

Licorice, turmeric, green tea, dandelion, perilla, Cheonggukjang, fenugreek, golden, pepper, 10g each sample was added and 20 times (v / w) of 50% EtOH was added and processed at 90W for 5 minutes using a microwave extraction device. Extracted by. The extract was filtered through filter paper, the solvent was evaporated with a reduced pressure rotary evaporator (Rotary Evaporator, Eyela, Japan) to 50% (v), and then filtered with a 0.45um syringe filter (Advantec, Japan) to give 5 weight of licorice. 5 parts by weight of turmeric, 20 parts by weight of green tea, 20 parts by weight of dandelion, 7 parts by weight of tea, 5 parts by weight of Cheonggukjang, 20 parts by weight of fenugreek, 20 parts by weight of gold, and 3 parts by weight of pepper are used in the following experiments. It was.

Example  2 : To Ovalbumin (OVA) Sensitized  mouse In splenocytes IL -4 production inhibitory activity

(1) Experimental method

BALB / c mice (6 weeks old) were injected twice a week at intervals of 1 week, prepared with 100 μl of a solution of OVA, an allergen of food allergen, and 2.25 mg of an adjuvant, alum, and injected into the abdominal cavity. Mice were dissected from the cervical spine and spleens were harvested aseptically to obtain splenocytes, and then 2x10 ⁶ cells per well were incubated with allergens (OVA, final concentration of 100 µg / ml) and respective extracts in 48-well plates. After 72 hours of incubation, the concentration of IL-4 produced in the supernatant was measured by sandwich ELISA (Sandwich Enzyme-linked immunosorbent assay). IL-4 measured here is a representative Th2 cytokine, and was used as an index for evaluating the Th1 / Th2 immune response regulatory activity of the extract.

IL-4 production inhibition rate (%)

       = 100-(IL-4 production in the sample treatment / IL-4 production in the control) x 100

(2) Experiment result

According to the results of Example 2, it was confirmed that the production of cytokine IL-4, which plays an important role in allergic development, was reduced in the treatment of each extract in an allergenic mouse experimental model using OVA. In particular, fenugreek, golden and green tea extracts showed a high IL-4 inhibitory activity of more than 75%, it was found that they can strongly regulate the immune response from Th2 to Th1.

Example  3: with A23187 PMA Induced to Degranulation  Inhibitory activity

(1) Experimental method

RBL-2H3 cell line derived from basophils was dispensed at 1 × 10 ⁶ cells / ml in a 24well plate and allowed to stand overnight to stabilize the cells, and then treated with extracts for each well and reacted for 1 hour. After the reaction, the stimulant (A23187 1 μM + PMA 50 nM) was treated for 8 hours, and then, the culture solution was recovered, and the histamine concentration in the supernatant obtained by centrifugation at 5000 rpm for 5 minutes was measured using the sandwich ELISA method.

Degranulation inhibition rate (%)

      = [(Control value-treatment value / / control value-blank value)] x 100

(2) Experiment result

According to the results of Example 3, it was confirmed that histamine release of RBL-2H3 cells induced by stimulants is inhibited by each extract treatment. In particular, over 55% was inhibited by the treatment of turmeric extract, dandelion and pepper extract.

Example  4 : Caco -2 Single cell layer  Passed food allergen test

(1) Experimental method

Human epithelial-derived Caco-2 cell line (HTB-37) was dispensed with 0.5 ml at a density of 5 × 10 ⁴ cells / well on the transmembrane, the apical side of the well of a 12 well plate. 1.5 ml of the culture medium was added to the basolateral side of the well and cultured in a 37% 5% CO ₂ incubator. About 2 ~ 3 weeks after dispensing, the transepithelial electrical resistance (TEER) value between the lower and upper layers of the Caco-2 cell layer was measured, and when the TEER value was> 300 Ω㎠, a stable single cell layer was formed and used for the allergen transit experiment. It was. The Caco-2 single cell layer was washed three times with HBSS buffer, and then bile acid (final concentration 150ug / ml and active substance (extract, final concentration 400㎍ / ml) was added to the upper layer, followed by 1 hour in 37 ° C 5% CO ₂ incubator. Then, 400 ug / ml of OVA was added to the upper layer, and after 3 hours in a 37 ° C. 5% CO ₂ incubator, the concentration of the OVA passed to the lower layer was measured by a sandwich ELISA.

The degree of passage to the bottom layer (pass rate, Flux) was calculated as follows.

Flux = C ng / H hr / S cm ²

Where C is the amount of OVA passage, H represents the reaction time after addition of OVA to the upper layer of Caco-2 single cell layer (eg 3hr), and S is Show the top surface area of the transwell plate (eg 1.1 cm ² ). At this time, the activity was compared and evaluated by expressing the change (inhibition, etc.) of the Flux generated by treating the active material in the upper layer as a relative value (%) relative to the Flux (100%) of the control group. In addition, when the TEER value of the case where no extract was added (control) was 100%, the relative TEER value (%) when the extract was added when the relative TEER value when the extract was added was 100%.

(2) Experiment result

¹⁾ Relative OVA pass rate (%) when 20 μl / ml sample was added when OVA pass rate (Flux) of (control) was not 100%

²⁾ Relative TEER value (%) when 20 μl / ml sample was added when the TEER value of (control) was not 100%

According to the experimental results of Example 4, in the food allergen (OVA) passage experiment using the Caco-2 single cell layer, it was confirmed that allergen passage was suppressed compared to the control when the extract treatment except pepper extract. In particular, when treated with golden, licorice, green tea and perilla extract, it was confirmed that the relative passage rate is lowered to 10% or less.

In addition, as a result of measuring the change in the TEER level, it was confirmed that the TEER level was increased compared to the control group when the remaining extracts were treated except pepper. In particular, fenugreek, dandelion and licorice extract were significantly increased by more than 150% compared to the control. This is believed to contribute to the inhibition of allergens by inhibiting the passage of allergens while maintaining a stable intestinal epithelial cell gap by extracts other than pepper.

Example  5: activity of anti-allergic composition

(1) Experimental method

A mixture of each extract was prepared as an antiallergic composition of the present invention, and the antiallergic activity of the nine mixtures was evaluated according to the test methods of Examples 2, 3 and 4. However, as shown in Table 4, the relative activities of each of the extracts and the nine mixtures selected above are shown as scores for each test method. In the case of IL-4 production inhibitory activity, the inhibition level was 20-40% +, 40-75% ++ and 75-100% +++, respectively, and degranulation inhibitory activity was 30 -40% was marked as +, 40-55% was marked as ++ and 55-100% was marked as +++. ++ and 35-50% are indicated with +, respectively.

(2) Experiment result

¹⁾ IL-4 production inhibition 20-40%: +, 40-75%: ++, 75-100%: +++

²⁾ Degranulation inhibition 30-40%: +, 40-55%: ++, 55-100%: +++

³⁾ Allergen passing degree 0-5%: +++, 5-35%: ++, 35-50%: +

⁴⁾ Mixture of 9 Extracts

According to the results of Example 5, the total score of each material extract was found to be 4+ to 8+, and the antiallergic composition prepared in Example 1 (9 mixtures) was found to be 9+. ”,“ Degranulation inhibition ”and“ Caco-2 single cell layer inhibition ”all showed high activity. Therefore, the anti-allergic composition presented in this patent application in terms of its mechanism of action (1) inhibits the uptake of allergens into the human body, and (2) induces the immune balance of Th1 / Th2, the first stage of allergy onset towards Th1. In addition, (3) by inhibiting the degranulation of mast cells, etc., which is the second stage of allergic development, an excellent effect is ultimately expected in the prevention and treatment of allergies.

Example  6: Effect of the composition of the present invention

(1) Experimental method

When animal experiments were performed using the composition in which the nine kinds of the present invention were mixed in the same ratio as in Example 1, anti-allergic activity was investigated. That is, in a BALB / c mouse (6 weeks old, 5 dogs per group), twice a week at a total of 2 weeks, an antigen of allergen OVA 20ug was mixed with 2.25mg of an adjuvant alum (alum) to prepare a 100ul solution. It was then injected into the abdominal cavity. After the second immunization, the anti-allergic composition was administered orally at a dose of 300 mg / kg once a day for a total of 10 days. Positive control dexamethasone was orally administered for 10 days at a dose of 0.5 mg / kg. On the last day, blood samples were collected and analyzed for antibody concentrations such as IgE in serum by sELISA, mice were degenerated from the cervical spine, and spleens were harvested aseptically to obtain splenocytes. 2x10 ⁶ cells per well were stored in 48-well plates. (OVA) 100 μg / ml and incubated with each extract. After 48-72 hours of incubation, the concentrations of cytokines such as IL-4 and IFNr produced in the supernatants were analyzed by sELISA.

(2) Experiment result

^* Significant differences were found at the level of 0.05% or less compared to the negative control.

According to the results of Example 6, the anti-allergic composition and the positive control (dexamethasone) in the [Table 5] showed a significant difference in the antibody production compared to the negative control, IgE and IgG1 antibodies related to allergy-induced production is inhibited And the production of IgG2a antibodies associated with allergic suppression has increased. Therefore, it was confirmed that the anti-allergic composition presented in the present invention strongly inhibits the first stage of allergic development in animal experiments. In addition, the anti-allergic composition and the positive control (dexamethasone) in the [Table 6] that examined the cytokines produced when the splenocytes were cultured in the presence of the antigen were all significantly different from the negative control, Th2 cytos associated with allergy-induced Caines IL-4 and IL-5 were inhibited in production, and production of Th1 cytokines IL-12 and IFNr, which were associated with allergic inhibition, was increased. In particular, the effect was more pronounced than the control group, which was much more effective than the steroid drug. Therefore, it was confirmed in animal experiments that the anti-allergic composition presented in this patent application strongly inhibits the first stage of allergic onset.

Example  7: Effect of the composition of the present invention

(1) Experimental method

       In the present invention, nine or more of the compositions mixed in the same ratio as in Example 1 were orally administered to experimental animals, treated with degranulation inducing agents, and their survival rates were examined. That is, 200 μl of the composition with different concentrations were administered to ICR mice (5 weeks old, 10 per group), and 1 hour later, intraperitoneally injected with compound 48/80 (compound 48/80) 200ul (8 mg / kg body weight) After 1 hour, survival was checked and expressed as percentage.

(2) Experiment result

^* Significant differences were found at the level of 0.05% or less compared to the negative control.

According to the results of Example 7, the anti-allergic effect was dependent on the concentration of oral administration of the anti-allergic composition in [Table 7], and a very high survival rate of 60% was obtained when 300 mg / kg was administered. Therefore, it was confirmed in animal experiments that the anti-allergic composition presented in this patent application strongly inhibits degranulation, which is closely related to the expression of allergic symptoms.

Example  8 Comparison of Comprehensive Effects on Compositions of the Invention

The composition obtained in Example 1 was compared with the A, B, and C food antiallergic compositions sold on the market using the experimental method of the present invention described in the above examples. The 10-point scale was used as the best and 10 as the best.

As a result of the above experiments, the composition of the present invention was found to exhibit a superior effect compared to the compositions commercially available from other companies.

Example 9 Preparation of Food Composition

Commercially purchased licorice 5g, turmeric 7g, green tea 15g, dandelion 17g, green tea 13g, Cheonggukjang 5g, fenugreek 15g, golden 20g, pepper 3g, 20 times weight (2kg) added 50% EtOH 5 minutes at 90W was used to extract the active ingredient. The extract was filtered through filter paper, the solvent was evaporated with a vacuum concentrator to 50% (v), and membrane filtered with a 0.45 um syringe filter to obtain a liquid composition (solid matter, 19.8 g).

Example  10: preparation of beverages

15 wt% of the food composition prepared in Example 9, 25 wt% of glucose, 0.5 wt% of citric acid, 0.5 wt% of nicotinic acid amide, 3 wt% of jujube concentrate and 51 wt% of purified water were mixed to sterilize the mixture at 110 ° C. for 10 seconds. To prepare a beverage.

Example 11 Preparation of Food Additives

15% by weight of the food composition prepared in Example 9, 55% by weight of calcium phosphate, 10% by weight of ferric pyrophosphate, 10% by weight of polyglutamine acid and 10 parts by weight of pentaglycerin monostearate and the above components were mixed well Water was added and stirred and mixed to prepare a slurry, and then wet grinding was performed using a wet grinding machine (Super Grind Mill, Seongchang Machinery, Korea) to obtain a food additive slurry composition. It was gradually heated at 80 ° C. for 4 hours, and it was powdered by spray drying after decompression and concentration.

Example 12 Preparation of Capsules

100 mg of the food composition prepared in Example 9, 30 mg of lactose, 70 mg of starch, 5 mg of stearic acid, and 2 mg of talc were mixed and prepared according to a conventional capsule preparation method.

Example 13: Preparation of Tablets

The food composition obtained in Example 9 was mixed with 200 mg of powder, 50 mg of lactose, 50 mg of starch, 2 mg of magnesium stearate, prepared by high pressure concentration, and then compressed into tablets according to a conventional manufacturing method.

Example  14 Preparation of Injection

20 mg of the food composition obtained in Example 9, 300 mg of mannitol, 5000 mg of sterile distilled water, 50 mg of Na ₂ HPO ₄ 12H ₂ O were mixed to prepare an injection according to a conventional method.

Claims (8)

 2-10 parts by weight of licorice, 2-10 parts by weight of turmeric, 10-30 parts by weight of green tea, 10-30 parts by weight of dandelion, 5-20 parts by weight of perilla, 2-10 parts by weight of Cheonggukjang, fenugreek 10 Food composition for the prevention and improvement of allergy containing -30 parts by weight, golden 10-30 parts by weight, and pepper 1-5 parts by weight of the extract as an active ingredient. A beverage for the prevention and improvement of allergies, characterized by containing 1-15% by weight of the food composition of claim 1 relative to the total weight. A food additive for preventing and improving allergy, characterized in that containing 1 to 15% by weight of the food composition of claim 1 relative to the total weight. Licorice 2-10 parts by weight, turmeric 2-10 parts by weight, green tea 10-30 parts by weight, dandelion 10-30 parts by weight, perilla 5-20 parts by weight, Cheonggukjang 2-10 parts by weight, fenugreek 10-30 parts, A pharmaceutical composition for preventing and treating allergy, consisting of 10-30 parts by weight of gold and 1-5 parts by weight of pepper. The food composition according to any one of claims 1 to 4, wherein the allergy is a food allergy. A component according to claim 1, wherein purified water and an aqueous alcohol solution are added 10-30 times by weight to extract using microwaves. 8. The method of claim 7, wherein the alcohol is a lower alcohol having 1 to 4 carbon atoms of 30-80%. The method of claim 7 or 8, wherein the microwave is treated for 2-30 minutes at 60 ~ 120W.