KR20090123179A - Composition comprising the extract of complex herb(sol-m) an active ingredient for preventing and treating allergy - Google Patents

Abstract

PURPOSE: A composition containing complex medicinal herb extract as an active ingredient is provided to suppress topical allergic reaction and general allergic reaction and prevent and treat allergic disease. CONSTITUTION: A pharmaceutical composition for preventing and treating allergic disease contains medicinal herb mixture extract of Rosin, Angelica dahurica and Phellodendri Cortex as an active ingredient in 1~15: 1~10: 1~10 of weight ratio(w/w). The medicinal herb extract is isolated using water, low alcohol of 1-4 carbon atoms or their mixture. The allergy is anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, contact dermatitis, urticaria, insect allergy, or food allergy. A functional health food for preventing and relieving allergic disease contains the medicinal herb complex extract as an active ingredient. The functional health food is used in the form of powder, granule, tablet, capsule or beverage.

Description

Composition comprising the extract of complex herb (Sol-M) an active ingredient for preventing and treating allergy}

The present invention relates to a pharmaceutical composition for the prevention and treatment of allergic diseases and health functional foods containing a combination herbal extract of rosin, white paper and yellow white as active ingredients.

[Document 1] Choi Byung-Hwi et al. 4, Allergy, 4 , pp 2-48, 2001

[2] Wuthrich B., Int. Arch. Allergy Appl. immunol. 90 , pp 3-10, 1989

Miller JS, et al, Curr Opin Immunol, 1 , pp 637-642, 1989

[4] Lee et al., Kor. J. of Dermatology, 28 (1) , pp 16-25, 1990

[Document 5] Park Yong-min, pediatric allergic respiratory system. 16 (3) , pp 189-196, 2006

[Document 6] Monthly Drug Information DI, Dermatology Diseases: Atopic Dermatitis, pp 8-13, 2005 (9)

7 Ennis et al., Br. J. Pharmacol, 70 , pp 329-334, 1980

8 Shin et al., Toxicol. Appl. Phamacol, 209 , pp 255-262, 2005

[Document 9] Jong-Hee Park, Encyclopedia of Herbal Medicine, Book Publishing Company, Il-il, pp. 484-486, 2002

[10] Jin et al., Kor. J. Pharmacogen, 35 (4) , pp 315-319, 2004

[11] Lee et al., Kor. J. Pharmacogen, 38 (4) , pp 387-393, 2007

12. Pearlman et al., J. Immunol, 151 , pp 4857-4864, 1993

[Document 13] Guideline for Functional Test on Cosmetics, Korean Institute of Health Procedures, pp 745-791, 2004

14 Inagaki et al., Eur. J. Pharmacol, 448 , pp 175-183, 2002

15] Kim et al. Exp. Biol. Med, 230 , pp 82-88, 2005

[16] Snapper and Paul, Science, 236 (4804) , pp 944-947, 1987

Allergy refers to a hypersensitivity reaction caused by contact with a harmless antigen, an allergen, which is innate or acquired and has an impaired immune function, such as anaphylaxis. , Allergic rhinitis, asthma, atopic dermatitis, insect allergies, food allergies, drug allergies, and urticaria (Cho Byung Hwi et al. 4, allergy, 4 , pp 2-). 48, 2001; Wuthrich B., Int. Arch.Allergy Appl. Immunol. 90 , pp 3-10, 1989).

Allergy is involved in the interaction of several factors, such as genetic predisposition, environmental factors, pharmacological abnormalities, immunological factors, etc. The hypersensitivity reaction of these immune functions is 4 It is divided into the types of branches. Type I hypersensitivity reactions occur when IgE (immunoglobulin E), which is excessively produced by repeated exposure of allergens, binds to mast cells, resulting in the release of granules containing histamine and the like. Anaphylatic shock or topical itching and inflammation are typical diseases, including atopic dermatitis (atopic dermatitis) and asthma (asthma). Type II hypersensitivity reactions induce hemocytopenia by the destruction of cells by Null (K) cells as antibodies bind to normal cells such as red blood cells, white blood cells, and platelets. Hemolytic anemia caused by cyclosporin ), Leukocyte reduction due to aminopyrine (leukopenia), platelet reduction due to quinidine (thrombocytopenia), and the like. Type 3 hypersensitivity is a disease in which polymorphonuclear (PMN) cells damage tissues by attaching antigen-antibody complexes to tissues, such as systemic lupuserythomatosis. On the other hand, type 4 hypersensitivity reactions are delayed type hypersensitivity reactions, in which sensitized T cells differentiate into memory cells and cause dermatitis when subsequently resensitized, called contact dermatitis. Is in the category of contact hypersensitivity (Miller JS, et al, Curr Opin Immunol, 1 , pp 637-642, 1989).

Atopic dermatitis is a very common disease that causes severe pruritus due to the low threshold of pruritus. Clinically, it is clinically determined by the age of the patient, from the infant type, which is characterized by skin lesions, to the adult type, in which the primary lesion is formed. Various clinical procedures are shown. In addition, patients with atopic dermatitis tend to be more sensitive to specific food or inhalation antigens than normal people, have a specific vascular response to various drugs or temperatures, and have a lower resistance to viruses that have a specific resistance to infection (Lee et al. , Kor.J. of Dermatology, 28 (1) , pp 16-25, 1990).

Atopic dermatitis is a chronic inflammatory skin disease common to the surroundings that occurs before other allergic diseases such as asthma, allergies and allergic rhinitis. It is estimated to account for 10 ~ 20% of the world's disease recently, and allergic to pediatric allergies due to increased airborne allergens due to air pollution and increased exposure to antigens due to changes in residential environment (migration to the city). According to the National Epidemiological Survey conducted by the Korean Respiratory Society in 1995 and 2000, the prevalence rate in Korea is also increasing from 15.3% to 17% (Park Yong-min, Allergic Respiratory Tract. 16 (3) , pp 189-196, 2006; monthly Pharmaceutical Information DI, Dermatology Diseases: Atopic Dermatitis, pp 8-13, 2005 (9)).

Most of atopic dermatitis is caused by an immune mechanism associated with immunoglobulin E (IgE). T cells that secrete IL-induced IgE production from B cells (interleukin, IL) -4, IL-5, which induces IgE production from B cells, and IL-6, which amplifies IgE production. Is a Th2 cell among CD4 T cells, and antigen-specific T cell clones isolated from peripheral blood and skin lesions of AD patients were found to be Th2, and it was demonstrated that cytokines such as IL-4 were secreted from these cells.

When allergens are recognized by IgE, they are adhered to Langerhans cell surface IgE-attached Fc receptors, and T lymphocytes are activated by delivering antigens to T lymphocytes. At this time, auto peptide or staphylococcus T lymphocytes can also be activated by superantigens of aureus ). Unlike other skin diseases, inflammatory cells infiltrating skin lesions of atopic dermatitis are mainly Th2 cells, which produce cytokines such as IL-4 and IL-5, which promote blood IgE elevation and eosinophils, and cAMP force Abnormal monocytes of atopic dermatitis with elevated phosphodiesterase increase PGE production, which inhibits infiltration of Th1 lymphocytes. Th1 lymphocytes are also released from splenocytes that are readily activated in atopic dermatitis. It is also inhibited by the tumor necrosis factor (TNF). Eventually, it suppresses Th1 proliferation in atopic dermatitis and causes a decrease in cell mediated immunity. Various cytokines (cytokines) is to induce or increase the expression of various cell adhesion molecules to activate endothelial cells by promoting the return of the memory T-lymphocytes to cause the eczema lesions (choebyeonghwi et 4, allergic, 4, pp 2- 48, 2001).

Mast cells are distributed in most organs and tissues and are important trigger cells for inflammatory reactions such as allergy and anaphylaxis. In particular, anaphylactic reactions are caused by histamine and various inflammatory cytokines released by the binding of IgE antigens bound to Fcε RI in mast cells, of which 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 that releases histamine from mast cells, it has been widely used for the study of prophylactic and therapeutic agents as well as for the study of anaphylactic reactions (Ennis et al., Br. J. Pharmacol, 70 , pp 329). -334, 1980; Shin et al., Toxicol. Appl. Phamacol, 209 , pp 255-262, 2005).

In recent years, urban people are increasingly exposed to various allergens, such as mites living on carpets in their homes, dust that increases with humidity, pet hair, pollen, new fruits and food. As a result, asthma and atopic dermatitis, type 1 hypersensitivity, have increased in recent years and become a social problem, many researchers have been focused on the search for substances that can mitigate immune hypersensitivity from natural products.

In addition, the exploration of new functional substances from natural products is accelerating with the establishment of the Korea Food and Drug Administration's notification on the evaluation of the efficacy and safety of functional foods and functional cosmetics and the approval procedure (Korean Health Procedures Research Association, 2004). In light of these social phenomena, the development of more effective new drugs through the scientification of natural products in a highly industrialized society has been recognized as an important factor in securing national competitiveness. Apart from various food sweeteners, fragrances, health functional foods, functional cosmetics, and natural pesticides, various developments have been made, but there is still insufficient research.

Rosin is a material extracted from pine pine rosin. Pine (Pinus densiflora Sieb et Zucc.) Is an evergreen conifer that grows in the Far East of Korea, Japan, and Manchuria, and all parts of leaves, pine cones, pollen, rosin, and bark have been used as vulcanized plants. Rosin is composed mainly of α-pinene, α-pinene, β-pinene and dipentene. The resin obtained by distilling essential oil from rosin is called rosin. Rosin has been reported to have pharmacological effects such as oxidation, antimicrobial, immune enhancement, and mutation suppression (Jong-Hee Park, Encyclopedia of Herbal Medicine, Shinil Corp., pp. 484-486, 2002).

The white paper (Angelica dahurica) is a perennial herb that grows in Korea's mountains and dried coarse roots before flowering. In oriental medicine, cold, headache, facial neuralgia, toothache, and postpartum It is known that there are about 20 kinds of coumarin components as the main herbal medicines for treating hematuria (Jin et al., Kor. J. Pharmacogen, 35 (4) , pp 315-319, 2004).

Phellodendri Cortex is a dried bark of peeled bark of Phellodendron amurense, Rhesus bark, Rhubarb or other species of the same family, which is used for conjunctivitis, cholecystitis, chronic colitis, and bacterial isolation. In oriental medicine, it is used as an inflammation, pneumonia, tuberculosis, cold fungicide, and anti-inflammatory medicine, and it is evaluated as a useful herbal medicine mainly used for infectious and disease. The main chemicals are steroids and steroids such as alkaloids such as berberine, palmatine and yaterorrhizine, limonin, and obacunone. Etc. It has been widely known that the antimicrobial effects including anti-inflammatory are excellent among the major herbal medicines listed above (Lee et al., Kor. J. Pharmacogen, 38 (4) , pp 387-393, 2007).

Up to now, none of the above documents teaches or describes that the combined herbal extracts of rosin, white paper and yellow white can be used as compositions for preventing and treating allergic diseases by inducing anti-allergic effects.

Accordingly, the present inventors have found that rosin, white paper and yellow-white complex herbal extracts suppress systemic allergic reactions and local allergic reactions, and are required to produce IL-4 and histamine, which are essential for the production of IgE, the main antibody of allergic reaction in allergic disease animal models. By confirming effectively inhibiting the anti-allergic effect was confirmed to complete the present invention.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of allergic diseases containing rosin, rouge (Angelica dahurica) and complex herbal extracts of Phellodendri Cortex as an active ingredient.

The present invention also provides a dietary supplement for the prevention and improvement of allergic diseases containing rosin, rosacea (Angelica dahurica) and complex herbal extracts of Phellodendri Cortex as an active ingredient.

The complex herbal extract as defined herein has a dry weight ratio (w / w) of rosin, white paper and sulfur white in the range of 1 to 15: 1 to 10: 1 to 10, preferably 1 to 10: 1 to 5: 1 to 5, more Preferably 1 to 5: 1 to 3: It is characterized by including 1 to 3.

Extracts as defined herein include water, including purified water, lower alcohols having 1 to 4 carbon atoms or solvents selected from mixed solvents thereof, preferably extracts soluble in water.

Allergic diseases as defined herein include hypersensitivity, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, contact dermatitis, urticaria, insect allergy, food allergy or drug allergy, preferably allergic rhinitis, asthma , Allergic dermatitis, atopic dermatitis, contact dermatitis, urticaria, food allergy or drug allergy, more preferably atopic dermatitis or asthma.

Hereinafter, the present invention will be described in detail.

Complex herbal extract of the present invention can be prepared as follows. A first step of mixing rosin, white paper and sulfur white in a dry weight ratio (w / w) of 1 to 15: 1 to 10: 1 to 10, preferably 1 to 10: 1 to 5: 1 to 5; As a solvent, preferably water, selected from water containing about 1 to 30 times the weight of the water, preferably 5 to 15 times the volume (w / v%) of purified water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof. A second step of extracting at a temperature of about 0 to 100 ° C., preferably at 20 to 100 ° C. for about 0.5 to 20 hours, preferably 1 to 15 hours; A third step of repeating the second step about 1 to 10 times, preferably 2 to 7 times; Through the manufacturing method comprising the fourth step of filtration concentrated and freeze-dried can be obtained the complex herbal extract of the present invention.

The present invention provides a pharmaceutical composition for the prevention and treatment of allergic diseases containing the complex herbal extract obtained by the above method as an active ingredient.

In addition, the present invention provides a health functional food for the prevention and improvement of allergic diseases containing the complex herbal extract obtained by the above production method as an active ingredient.

The pharmaceutical composition for the prevention and treatment of allergic diseases containing the complex herbal extract of the present invention comprises 0.1 to 50% by weight of the complex herbal extract based on the total weight of the composition.

However, the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.

The pharmaceutical composition containing the complex herbal extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

The pharmaceutical compositions containing the complex herbal extracts according to the present invention may be prepared in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively. It can be formulated and used in the form. Carriers, excipients and diluents that may be included in the composition containing the extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber , Alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil have. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose in the compound. Mixed with gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The amount of the composite herbal extract of the present invention may vary depending on the age, sex, and weight of the patient, but may be 0.1 to 100 mg / kg, preferably 1 to 10 mg / kg once or several times daily. The dosage may also be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The pharmaceutical composition may be administered to various mammals such as mice, mice, livestock, humans, and the like. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.

The present invention provides a health functional food for the prevention and improvement of allergic diseases containing rosin, white paper, and complex white herbal extract as an active ingredient. Foods to which it may be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, tea vitamin complexes, and health functional foods.

Since the extract itself of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for a long time for the purpose of prevention.

The extract of the present invention may be added to food or beverages for the purpose of preventing and improving allergic diseases. At this time, the amount of the composite herbal extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health functional beverage composition is added in a ratio of 0.02 to 10g, preferably 0.3 to 1g based on 100ml Can be.

The functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the extract as an essential ingredient in the indicated proportions, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. have. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above, the herbal extract of the present invention may be used in various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors such as flavoring agents, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain pulp for the production of natural fruit juices and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

As described above, the complex herbal extracts of Rosin, Angelica dahurica, and Phellodendri Cortex of the present invention inhibit systemic allergic reactions and local allergic reactions, and allergic reactions in animal models of allergic diseases. It shows an excellent effect of inhibiting the production of IL-4 and histamine, which are essential for the production of IgE, which is a major antibody, and can be used as a pharmaceutical composition and health functional food for the prevention and treatment of allergic diseases.

Hereinafter, the present invention will be described in detail.

However, the following Examples, Reference Examples and Experimental Examples are merely illustrative of the present invention, but the content of the present invention is not limited thereto.

Reference Example  1. Preparation of experimental animals

Given that anaphylaxis development is due to the short-term overproduction of allergens, particularly IgE or IgGI, that is, the activation of type-2 helper-T cells that produce IL-4, which induces such antibodies in the body, is readily induced. Four-week-old BALB / c (Pearlman et al., J. Immunol, 151 , pp 4857-4864, 1993) mice were supplied from Orient Co., Ltd. (Seongnam, Gyeonggi-do) and used for about one week after laboratory purification. Two mice were housed in a cage for mice (220 × 200 × 145 mm). The environment of the animal laboratory was controlled at a temperature of 21-25 ° C, a relative humidity of 45-65%, a frequency of 12 ventilations / hour, a lighting cycle of 12 hours (07:00-19:00), and an illumination intensity of 150-300 lux. Purina Rat Chow, a pellet-type solid feed for experimental animals, was supplied from Biopia (Gunpo, Gyeonggi-do). All animal experiments in this study were performed in accordance with the Standard Operation Procedure (SOP) with the approval of the Institutional Animal Care and Use Committee (IACUC).

Reference Example  2. Statistical Analysis

Levene's test was performed to compare the homogeneity of the variances for each experimental result.If the variances were homogeneous, one-way analysis of variance (ANOVA) was observed. Dunnett t- test was performed to identify the test group with statistical differences. It was determined that there was statistical significance when the difference was less than 5% ( p <0.05).

Example  One. rosin , Blank and Yellow-white  Preparation of Complex Herbal Extract

Rosin powder was supplied from Solbin Co., Ltd. (Naesu-eup, Cheongwon-gun, Chungbuk), and Baekji and Hwangbaek were purchased from Daegu Yangnyeong Market. About the sample, 10 times of distilled water was added to a 100 g sample in which rosin, white paper, and yellow and white powder were mixed at a gram ratio of 3: 1: 1, extracted with water at 80 ° C. for 8 hours, and then cooled. The filtrate was filtered through a filter cloth, and the filtrate was concentrated under reduced pressure using a reduced pressure concentrator (NE-1, EYELA, Japan). The filtrate was freeze-dried to obtain 7.5 g of a composite herbal extract of rosin, white paper, and yellow white, which were used as samples in the following experimental example. (Hereinafter referred to as “Sol-M”).

Experimental Example  1. Systemic allergy  Measurement of reaction inhibitory effect

In order to determine the systemic allergic reaction inhibitory effect by the rosin, white paper and yellow white complex herbal extract (Sol-M) prepared in Example 1, the experiment was carried out as follows (Beauty related functional test guidelines, Korean health process Seo Research Society, pp 745-791, 2004) . The BALB / c mice of Reference Example 1 were orally administered with Sol-M (50, 100, 200 mg / kg) once a day for 6 days. 30 minutes after the last dose, anaphylactic shock by intraperitoneal injection of a lethal dose (8 mg / kg) mast cell degranulator compound 48/80 [50 μg / site, 50 μl at 1 mg / ml] After induction of (anaphylactic shock), the mortality rate of the mice compared to the control group (pharmaceutical 0 μg / ml) administered only intraperitoneally with saline solution and the experimental group for 60 minutes was expressed as a percentage.

As a result, Sol-M showed 30% survival at 50 mg / kg, 50% survival at 100 mg / kg, and 60% survival at 200 mg / kg. Compared with the effects of 50 and 100 mg / kg, the most effective systemic allergic reaction was suppressed with a survival rate of 60% at the dose of 200 mg / kg.

From these results, it was confirmed that Sol-M of the present invention blocks the process by which IgE releases histamine from mast cells by compound 48/80 (see Table 1). ).

Experiments Treatment ( mg Of kg ) Compound  48/80 ( mg Of kg ) Mortality  (%) Vehicle (saline) - 8 100 Sol-M 50 8 70 Sol-M 100 8 50 * Sol-M 200 8 40 **

Experimental Example  2. Locality allergy  Reaction (Atopic dermatitis) inhibitory effect experiment

In order to measure the atopic dermatitis improvement effect by the combined herbal extract of rosin, white paper and yellow white of Example 1 (Sol-M), the experiment was performed as follows (Beauty related functional test guidelines, Korea Korean Institute of Health Process Studies, pp 745-791, 2004 .

The BALB / c mice of Reference Example 1 were orally administered with Sol-M (50, 100, 200 mg / kg) once a day for 6 days. Thirty minutes after the last dose, 5 ml / kg of 1% Evan's blue was injected intravenously into the mouse vein and compound 48/80 [mast cell degranulator] compound 48/80 [50 μg / site, 1 50 μl in mg / ml] was injected intradermal (Inagaki et al., Eur. J. Pharmacol, 448 , pp 175-183, 2002). The number of scratching behaviors was recorded for 30 minutes after Compound 48/80 administration.

After measuring the number of itching, the blood was perfused through the left ventricle with 100 ml / kg saline to remove systemic blood, and the size of the subcutaneous bleeding spot was measured by removing the skin at the Compound 48/80 injection site. The skin containing the bleeding spots was cut out and placed in 1 ml of formamide for 3 days and the absorbance was measured at 620 nm to quantify Evans Blue (Kim et al, Exp. Biol. Med, 230 , pp 82-88, 2005 ).

The results showed that the normal control group exhibited 17.6 ± 35.3 scratching behaviors, whereas the solvent was orally administered for 6 days and injected compound 48/80 [50 μg / site, 50 μl at 1 mg / ml] intradermally. One mouse showed a 476% increase in scratching behaviors of 83.4 ± 33.1 in the first trial for 30 minutes (see Table 2). In contrast, 96.7 ± 78.5 (552%) at 50 mg / kg, 81.6 ± 45.9 (466%) at 100 mg / kg, and 47.3 ± 35.8 (270%) at 200 mg / kg. It showed the effect of inhibiting itching of the skin.

Experiments Treatment ( mg Of kg ) Compound  48/80 (μg / site ) Scratching behaviors ( counts / 30 min ) Normal - - 17.6 ± 35.3 Vehicle - 50   83.4 ± 33.1 ‡ (476%) Sol-M 50 50  96.7 ± 78.5 ‡ (552%) Sol-M 100 50  81.6 ± 45.9 ‡ (466%) Sol-M 200 50 47.3 ± 35.8 ‡ * (270%)

In addition, in the area of skin edema (Evan's blue leakage) caused by allergic reactions such as skin itch, the results similar to the skin itch inhibitory effect, that is, the correlation between the area of edema and the concentration of Evan's blue showed a significant correlation. 3).

Through these experimental results, Sol-M of the present invention, in addition to histamine that causes itching in atopic dermatitis, heparin, platelet-activating factor, prostaglandins, rucotriene ( It is possible to alleviate itching and edema at the same time by generally suppressing the secretion of these inflammatory reactants, such as leukotrienes.

Experiments Treatment ( mg Of kg ) Compound  48/80 (μg / site ) Evan's blue leakage mm ² μg Normal - - 4.5 ± 8.8 0.2 ± 0.2 Vehicle - 50 98.5 ± 43.1 ‡  3.5 ± 1.3 ‡ Sol-M 50 50 68.4 ± 32.3 ‡ 3.1 ± 1.5 ‡ Sol-M 100 50 51.6 ± 34.7 ‡ * 2.4 ± 0.7 ‡ * Sol-M 200 50 49.6 ± 16.6 ‡ * 2.1 ± 0.6 ‡ *

Experimental Example  3. In serum IgE Of the inhibitory effect of

In order to measure the inhibitory effect of the production of IgE in serum by Sol-M obtained in Example 1, the experiment was performed as follows using an ELISA (BD OptEIA ^™ ELISA set, BD Bioscience) method.

BALB / c mouse of Reference Example 1 was anesthetized with ether, blood was collected from the posterior vena cava of the mouse, blood was separated and centrifuged at 3,000 rpm for 10 minutes to separate serum, and the separated supernatant was -20 ° C. Measured while stored in (BD OptEIA ^™ ELISA set, BD Bioscience).

As a result, the effect of inhibiting the production of IgE in serum by Sol-M of the present invention was 826 ± 128 (ng / ml) in the normal control group, while 1476 ± 209 (ng) in the control group without the test substance. / ml) significantly increased by 178% and 167, 157, 136% in the 50, 100, 200 mg / kg group, which was significantly increased compared to the normal control group ( p <0.01 ~ <0.05). Compared to the control group, the control group showed a tendency to be significantly inhibited. In particular, the 200 mg / kg group showed a 76% superior inhibitory effect ( p <0.05), and the amount of IgE in serum by Sol-M Was confirmed to be inhibited (see Table 4).

Experiments Treatment  ( mg Of kg ) Compound  48/80 (μg / site ) Serum IgE levels ( ng Of ml ) Normal - - 826 ± 128 Vehicle - 50 1476 ± 209 ‡ (178%) Sol-M 50 50 1386 ± 186 ‡ (167%) Sol-M 100 50 1297 ± 197 † (157%) Sol-M 200 50 1124 ± 108 * (136%)

Experimental Example  4. Histamine in serum ( histamine Measure the inhibitory effect of

In order to measure the inhibitory effect of the release of histamine in serum by Sol-M, an experiment was performed using the ELISA (IBL, Hamburg, Germany) method as follows.

BALB / c mice of Reference Example 1 were anesthetized with ether, blood was collected from the posterior vena cava of the mouse, and blood was separated, and then serum was separated by centrifugation at 3,000 rpm (MF-300, Hanil Science and Industry, Korea) for 10 minutes. After that, the separated supernatant was measured while stored at -20 ° C (IBL, Hamburg, Germany).

As a result, the inhibitory effect of histamine release by Sol-M was shown to be 70 and 64% in the 100 and 200 mg / kg administration groups, respectively, to inhibit the release of histamine in serum by Sol-M. It could be confirmed (see Table 5).

Experiments Treatment ( mg Of kg ) Compound  48/80 (μg / site ) Histamine levels  ( ng Of ml ) Normal - - 19 ± 2 Vehicle - 50 138 ± 26.4 ‡ (726%) Sol-M 50 50 119 ± 19.7 ‡ (626%) Sol-M 100 50 96.9 ± 36.7 ‡ * (70%) Sol-M 200 50 89.4 ± 29.7 ‡ * (64%)

Experimental Example  5. From splenocytes IL To measure the inhibitory effect of -4

In order to measure the inhibitory effect of Th2 cytokine production centering on IL-4 inducing IgE from splenocytes by Sol-M, the following ELISA (BD OptEIA ^™ ELISA set, BD Bioscience) method was used. The experiment was performed as (Snapper and Paul, Science, 236 (4804) , pp 944-947, 1987).

The BALB / c mice of Reference Example 1 were orally administered with Sol-M (50, 100, 200 mg / kg) once daily for 6 days. Thirty minutes after the last dose, necropsy and spleens were aseptically harvested from each mouse, followed by dispensing 1 × 10 ⁴ / well of IL-4 cells in a 96-well cell culture plate. At this time, immobilized anti-CD3 mAb (5 ug / 5x10 ⁵ cells, BD Pharmagen, San Jose, CA) was used as a polyclonal stimulator for in vitro activation of T-lymphocytes. , 100, 200 μg / ml) for 18 hours. After incubating for 48 hours in a 37 ° C., 5% CO ₂ incubator with 20 μl of MTS solution per well, absorbance at 450 nm was measured using a Microplate Scanning Spectrophotometer (BD OptEIA ^™ , USA) to induce IgE. We compared the production capacity of Th2 cytokine (IL2)-based cytokine (IL-4) to evaluate the bias towards Th2 immune response.

As a result, the amount of IL-4 produced due to allergy induction was 19.9 ± 2.7 pg / ml, whereas in Sol-M (200 mg / kg), it was represented as 13.1 ± 3.5 pg / ml. It was confirmed that the production of IL-4, an allergen, was suppressed (see Table 6).

Experiments Treatment ( mg Of kg ) Compound  48/80 (μg / site ) IL -4 levels ( pg Of ml ) Normal - - 8.3 ± 1.9 Vehicle - 50 19.9 ± 2.7 ‡ (239%) Sol-M 50 50 16.3 ± 2.9 ‡ (196%) Sol-M 100 50 17.5 ± 3.4 ‡ (210%) Sol-M 200 50 13.1 ± 3.5 * (65%)

As a result, the combined herbal extracts of rosin, white paper, and baekbaek inhibit systemic allergic reactions and local allergic reactions, and confirm excellent inhibitory effects on IL-4 and histamine, which are essential for the production of IgE. Extract seems to have potential as an allergy therapeutic and prophylactic agent.

Examples of the formulation of the composition comprising the extract of the present invention will be described, but the present invention is not intended to limit it, but is intended to explain in detail only.

Formulation Example 1 Preparation of Powder

       Sol-M Extract 20 mg

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

Sol-M Extract 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

Sol-M Extract 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

Sol-M Extract 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _4, 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation Example 5 Preparation of Liquid

Sol-M Extract 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added to the mixture, and then the above ingredients are mixed, purified water is added to adjust the total amount to 100 ml, and then filled in a brown bottle. The solution is prepared by sterilization.

Formulation Example 6 Preparation of Healthy Food

Sol-M Extract 1000mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health functional food in a preferred embodiment, the composition ratio may be arbitrarily modified, and the above components may be mixed according to a conventional health food manufacturing method. Next, the granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation example  7. Manufacture of health drinks

Sol-M Extract 1000mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components according to the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored Used to prepare the healthy beverage composition of the invention.

Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Claims (7)

A pharmaceutical composition for the prevention and treatment of allergic diseases, which contains a combination herbal extract of Rosin, Angelica dahurica and Phellodendri Cortex as active ingredients. The pharmaceutical composition according to claim 1, wherein the complex herbal extract has a dry weight ratio (w / w) of rosin, white paper, and sulfur white in the range of 1 to 15: 1 to 10: 1 to 10. The pharmaceutical composition according to claim 1, wherein the extract is an extract available from a solvent selected from water including purified water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The pharmaceutical composition of claim 1, wherein the allergic disease is hypersensitivity, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, contact dermatitis, urticaria, insect allergy, food allergy or drug allergy disease. The pharmaceutical composition according to claim 1, wherein the extract comprises 0.1 to 50% by weight of the total weight of the composition. Health functional food for the prevention and improvement of allergic diseases containing Rosin, Angelica dahurica and Phellodendri Cortex complex herbal extract as an active ingredient. 7. The dietary supplement of claim 6 which is a powder, granule, tablet, capsule, syrup or beverage.