KR20080023570A - Composition comprising the extract of salvia miltiorrhiza bunge for the prevention and treatment of asthma and allergic disease - Google Patents

Abstract

A composition comprising the extract of Salvia miltiorrhiza BUNGE is provided to inhibit production of leukotriene C4(LTC4) depending on 5-LOX(5-lipoxygenase), production of prostaglandin D2(PGD2) depending on COX-2(cyclooxygenase-2), and degranulation in mast cells, so that the composition is useful for prevention and treatment of asthma and allergic disease. A composition for prevention and treatment of asthma and allergic disease including bronchial asthma, allergic rhinitis, allergic asthma and allergic dermatitis comprises the crude extract of Salvia miltiorrhiza BUNGE which is prepared with water, C1-C4 lower alcohol or a mixed solvent thereof, the polar solvent extract of Salvia miltiorrhiza BUNGE which is prepared with water, methanol, ethanol, butanol or a mixed solvent thereof, or the non-polar solvent extract of Salvia miltiorrhiza BUNGE which is prepared with hexane, chloroform or ethylacetate, and is a pharmaceutical or health food composition having a formulation of powder, granule, tablet, capsule or drink.

Description

Composition comprising the extract of Salvia miltiorrhiza BUNGE for the prevention and treatment of asthma and allergic disease}

1 is a rat bone marrow-derived mast cells to the Salvia miltiorrhiza extract produced (mouse bone marrow-derived mast cells , BMMC) on the cyclooxygenase -2 (cyclooxygenase-2, COX- 2) dependent prostaglandin D ₂ (prostaglandin D ₂₎ Is a diagram showing the effect of suppressing,

2 is a diagram showing the inhibitory activity test results of 5-lipoxygenase (5-lipoxygenase) involved in (leukotriene C ₄₎ Synthesis of leukotrienes C ₄ to cause bronchial asthma and allergic reactions,

      Figure 3 is a diagram showing the experimental results of the free inhibitory response of beta-hexosaminidase (β-hexosaminidase, β-HEX) indicative of degranulation in mast cells causing various inflammatory diseases, bronchial asthma and allergic reactions,

     FIG. 4 is a diagram showing the results of passive cutaenous anaphylaxis inhibitory response to the rat, a representative type I allergic model for knowing the anti-allergic ability in vivo to salvia extract.

    Allergic diseases are most often caused by mast cells in tissues activated by antigen-antibody reactions and by basophil cells in blood and eosinophils (primarily histamine, leukotrienes, TNF-α, cytokines, etc.). Since the use of allergy therapeutic drugs currently used remains symptomatic, there is an urgent need for the development of more fundamental therapeutic drugs.

Key mediators to induce asthma and allergic diseases are prostaglandin acids (prostaglandindes), leukotriene acids (leukotriens), platelet activating factor (PAF), etc. is phospholipase _{A 2 (phospholipase A 2, PLA} 2) and cyclooxygenase It is produced from arachidonic acid which is a precursor by cyclooxygenase-2 and lipoxygenase.

    In order to treat the above asthma and allergic diseases, various kinds of inflammatory disease treatments have been developed. The inflammatory disease therapeutic substances reported to date are tissue cells damaged in acute inflammation, cells involved in inflammation, or chemotactic factor. It is a drug that inhibits the production of eicosanoids from the cell membrane of leukocytes induced by. Allergy agents are also drugs that inhibit histamine free inhibition, histamine receptor blockade, leukotriene production inhibition and leukotriene receptor blockade, which are released during antigen-antibody reactions.

On the other hand, drugs recently attracting attention as an allergic agent for treating asthma are drugs having both histamine free inhibition, leukotriene C ₄ production inhibition, and platelet activator inhibitor activity.

Crude Salviae extract contains a phenolic compound and is known to have effects such as hepatocyte protection and red blood cell oxidation (Li, et al., Journal of Asian Natural Products Research 4 (4) , pp 271-280, 2002; Liu, P. et al., Liver 21 (6) , pp 384-390, 2001). The active ingredients are tanshinones, D (+) 3,4-dihydroxyphenol lactic acid (D (+) 3,4-dihydroxyphenol lactic acid), protocatechuic aldehyde, salvianoline acid (salvianolic acids (A, B, C, D, E, F)), rosmarinic acid are known (Li, et al., Journal of Chinese Pharmaceutical Science 6 , pp. 5764, 1997; Wang, et al., Acta Acad . Med. Shanghai 18 , pp. 2732, 1991).

The root of Salvia Miltiorrhiza contains tanshinone I, II _{A ,} II _{B ,} dihydrotansinone, cryptototansinone, methyl tanshinoate, methylene tansyquinone and β-sitosterol. (Hyang Yak Dictionary, Shin Min Kyo, Jung Sup Kim, pp. 861, 1989)

      Despite these studies, studies on asthma and allergic diseases of Salvia ginseng are still insignificant, and there are no studies on lipid mediators that specifically cause asthma and allergic diseases.

Therefore, the present inventors strongly inhibit COX-2 dependent PGD ₂ production in mast cells, which are the main cells involved in asthma and allergic diseases, and at the same time, 5-LOX dependent leukotriene C ₄ (LTC). ₄ ) The present invention was completed by confirming that there is an effect of strongly inhibiting the production and degranulation reaction.

An object of the present invention is to provide a pharmaceutical composition and health functional food for the prevention and treatment of asthma and allergic diseases containing crude extract, polar solvent soluble extract or non-polar solvent soluble extract of salvia as an active ingredient.

      In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of asthma and allergic diseases containing crude extract, polar solvent soluble extract or non-polar solvent soluble extract of salvia as an active ingredient.

     The present invention also provides a health functional food for the prevention and improvement of asthma and allergic diseases containing crude extract, polar solvent soluble extract or non-polar solvent soluble extract of salvia as an active ingredient.

    The crude extract as defined herein is an extract available in a solvent selected from water including purified water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water and an ethanol mixed solvent, more preferably 50 to 90% ethanol. Means an extract available in a mixed solvent.

    The polar solvent soluble extract as defined herein is an extract soluble in a solvent selected from water, methanol, ethanol, butanol or a mixed solvent thereof, preferably butanol, and the nonpolar solvent soluble extract is hexane, chloroform, methylene chloride, ethyl acetate , Glycerine, butylene glycol, preferably means an extract soluble in ethyl acetate.

In addition, asthma and allergic diseases as defined herein, lipoxygenase (5-LOX, 5-lipoxygenase ) dependent leukotriene C ₄ inhibit the generation of _{(leukotriene C 4, LTC 4)} , cyclooxygenase -2 (COX-2 , cyclooxygenase-2) -dependent prostaglandin (prostaglandin D ₂ , PGD ₂ ) is characterized in that it is due to the inhibition of degranulation reaction in mast cells (mast cells).

      The allergic disease includes one or more diseases selected from bronchial asthma, allergic rhinitis, allergic asthma, allergic dermatitis, preferably bronchial asthma, allergic rhinitis.

      Hereinafter, the method for obtaining the crude extract, the polar solvent soluble extract or the non-polar solvent soluble extract of the present invention will be described in detail.

Crude extract of the present invention, about 1 to 20 times the weight (kg) by cutting the root or ground portion (leaf, stem) of dried salvia, preferably about 3 to 10 times the water, C ₁ To lower alcohols of C ₄ or a mixed solvent thereof, preferably water or methanol, at an extraction temperature of 20 ° C. to 100 ° C., preferably 50 ° C. to 100 ° C., for about 1 hour to 10 days, preferably about 2 Extraction liquid obtained by using a cold needle, hot water extraction, ultrasonic extraction, reflux cooling extraction method for a time to 5 hours can be obtained by filtration, concentrated under reduced pressure or dried.

In addition, the non-polar solvent soluble extract of the present invention, after suspending the crude extract in distilled water, the suspension is about 1 to 100 times, preferably about 1 to 5 times the volume of hexane, chloroform, methylene chloride, ethyl acetate, preferably Is a non-polar solvent soluble layer is extracted once and 10 times, preferably 2 to 5 times by adding a non-polar solvent such as ethyl acetate to obtain a non-polar solvent soluble extract soluble in a non-polar solvent, the polar soluble in a polar solvent Solvent soluble extracts can be separated. It is also possible to further carry out conventional fractionation processes (Harborne JB, A guide to modern techniques of plant analysis . 3 , pp 6-7, 1998).

   The composition of the present invention preferably contains 0.01 to 99.9% of Salvia extract, more preferably 0.1 to 90%.

    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 composition comprising the extract of Salvia Militiorrhiza may further include appropriate carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

     Compositions comprising extracts according to the invention are formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Carriers, excipients and diluents which may be used in combination with the extract, and which may be included in the composition comprising the extract 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. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspending agents, liquid solutions, 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.

Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

     The composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

     The present invention provides health for the prevention and improvement of asthma and allergic diseases, including crude extracts, polar solvents or non-polar solvent soluble extracts, and food supplements of food supplements that are effective in preventing and improving asthma and allergic diseases. Provide nutraceuticals.

      The composition comprising the extract of the present invention can be used in various ways, such as drugs, foods and drinks for the prevention and improvement of asthma and allergic diseases. Examples of foods to which the polar and non-polar solvent soluble extracts of the present ginseng can be added include various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, powders, granules, tablets, capsules, or the like. It can be used in the form of a drink.

     Crude extract, polar solvent or non-polar solvent soluble extract itself of the present invention is a drug that can be used with confidence even for long-term administration for the purpose of prevention because there is little toxicity and side effects.

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

     In addition to containing the extract as an essential ingredient in the indicated proportions, the health beverage composition of the present invention has no particular limitation on the liquid component, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like. Sugars 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 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 composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

        Hereinafter, the present invention will be described in detail by Examples and Experimental Examples.

       However, the following Examples and Experimental Examples are only illustrative of the present invention, and the content of the present invention is not limited to the following Examples and Experimental Examples.

Example  One. Salvia Crude extract  Produce

1-1. Sweet ginseng Hydrothermal extract  Manufacturing method

     1kg of Korean sweet ginseng purchased from Gyeongdong market was heated in 50ml purified water for 15 minutes to obtain 360g of hot water extract. (Yield: 36%)

1-2. Sweet ginseng 70% Method for preparing ethanol mixed solvent soluble extract

     1kg of Korean salvia, purchased at Gyeongdong Market, was extracted with 70% ethanol at 70 ° C. for 5 hours, and the extract was filtered through 0.45 μm filter paper, and the filtrate was concentrated and freeze-dried to obtain 206 g of 70% ethanol extract of salvia. (Yield: 20.6%)

Example  2. Salvia Nonpolar Solvent  And preparation of a polar solvent soluble extract

2-1. Sweet ginseng  Method for preparing chloroform soluble extract

     50 g of the ethanol mixed solvent soluble extract of Example 1-2 was dissolved in 500 ml of water, extracted and fractionated three times with chloroform, the chloroform soluble layers were combined, and the solvent was evaporated using a rotary evaporator to obtain 15.4 g of a chloroform soluble extract. (Yield: 30.8%)

2-2. Sweet ginseng  Method for preparing ethyl acetate soluble extract

     The remaining layer (supernatant), except for the chloroform soluble extract of Example 2-1, was extracted and fractionated three times with ethyl acetate, the ethyl acetate soluble layers were combined, and the solvent was evaporated with a rotary evaporator to give 11.6 g of ethyl acetate soluble extract. Got. (Yield: 23.2%)

2-3. Sweet ginseng Butanol  Method for preparing soluble extract

The remaining layer (lower layer) except for the ethyl acetate soluble extract of Example 2-2 was extracted and fractionated three times with butanol, the butanol soluble layers were combined, and the solvent was evaporated with a rotary evaporator to obtain 3.8 g of butanol soluble extract. (Yield: 7.5%)

Experimental Example  Prostaglandins D ₂  Investigate the impact on biosynthesis

70% ethanol extract, chloroform soluble extract, ethyl acetate soluble extract, butanol soluble extract and hot water extract obtained in Examples 1 to 3, prostaglandin D ₂ In order to examine the effect on the production of (PGD ₂ ) it was experimented as follows using the method described in the literature. (Lee et al., Biol . Pharm . Bull . 27 (6) , pp . 786-788, 2004)

Mouse bone marrow-derived mast cells (BMMC) were derived from BALB / C mice by Murakami et al. [Murakami et al .; J. Biol . Chem . 269 , 22269-22275 (1994)], a medium under 50% WEHI-3 conditions containing culture supernatant of WEHI-3 cells (provided by Professor Kudo Ichiro, Pharmacy, Showa University, Japan) conditioned medium, containing 10% FCS).

After 3 weeks of culture, mast cells were treated with SCF / LPS / IL-10 mixed stimulant (Sigma) for 30 minutes. PGD ₂ quantification of the supernatant after cell stimulation was measured by Enzyme linked immunoassay (EIA) using the PGD ₂ assay kit (Cayman).

At this time, in order to suppress the production of PGD ₂ produced by COX-1, BMMC was treated with aspirin (aspirin, 10 ug / ml) 1 hour beforehand in BMMC. Anthricin was pre-treated for 15 minutes in advance, and the amount of PGD ₂ produced by adding a stimulant was measured. In addition, the production of PGD ₂ by cyclooxygenase-1 (COX-1) was measured 1 hour after treatment with SCF / LPS / IL-10 mixed stimulant (Sigma). It is shown in Table 1 below. (See Figure 1)

sample 50 μg / ml % Inhibition 70% Ethanol Extract 100 Chloroform Soluble Extract 50 Ethyl acetate soluble extract 80 Butanol Soluble Extract 40 Hot Water Extract 30

As a result, COX-2 dependent PGD ₂ production inhibitory activity in the bone marrow-derived mast cells at 50 ㎍ / ml concentration was confirmed that the strong activity in the 70% ethanol extract and ethyl acetate fraction.

  In addition, as a result of confirming dose dependency using 70% ethanol extract, the concentration required for 50% inhibition was 3.96 ㎍ / ml, indicating a strong inhibitory activity.

Experimental Example  2. Leukotrien  Impact Analysis Experiments on Generation

In order to examine the effect of 70% ethanol extract, chloroform soluble extract, ethyl acetate soluble extract, butanol soluble extract and hot water extract on leukotriene C ₄ (LTC ₄ ) production obtained in Example 1, Experiment was as follows. (Lee et al., Biol . Pharm . Bull . 27 (6) , pp . 786-788, 2004)

Mast cells derived from murine bone marrow were harvested from BALB / C mice by Murakami et al. [Murakami et al .; J. Biol . Chem . 269 , 22269-22275 (1994)], a medium under 50% WEHI-3 conditions containing culture supernatant of WEHI-3 cells (provided by Professor Kudo Ichiro, Pharmacy, Showa University, Japan) conditioned medium, containing 10% FCS).

After 3 weeks of culture, mast cells were treated with SCF (Sigma) for 30 minutes. LTC ₄ quantification of the supernatant after cell stimulation was measured by EIA using the LTC ₄ assay kit (Cayman). After pre-treatment of each extract for 15 minutes in advance, the amount of LTC ₄ produced by adding a stimulant was measured, and the results are shown in Table 2 below.

sample 50 μg / ml Inhibition Rate (%) 70% Ethanol Extract 95 Chloroform Soluble Extract 60 Ethyl acetate soluble extract 90 Butanol Soluble Extract 50 Hot Water Extract 40

    As a result, it was confirmed that 5-LO dependent PGD2 production inhibitory activity in the bone marrow-derived mast cells at a concentration of 50 ㎍ / ㎖ showed a strong activity in 70% ethanol extract and ethyl acetate fraction.

   In addition, as a result of measuring the dose dependency using the 70% ethanol extract, it was confirmed that the concentration required for 50% inhibition showed a strong inhibitory activity as 0.56 ㎍ / ㎖. (See Figure 2)

Experimental Example  3. Mast Cells Degranulation  Affecting compound saucerneol  Effect of B (β-Hexosaminidase, β- HEX )

The mouse bone marrow-derived mast cells (BMMC) prepared in Experimental Example 2 were treated with ₂ % 10 ⁵ cells / ml of the compound 70% ethanol fraction by concentration (3.125-50 ㎍ / ml) at 37 ° C. and 5% CO _2. SCF (KL, c- kit ) after preincubation for 30 minutes under conditions ligand, 100 ng / ml) was incubated for 15 minutes and centrifuged for 5 minutes at 3000rpm, 4 ℃. The supernatant was mixed 1: 2 with β-hex (substrate [100 mM citrate buffer (citric acid 0.955%, sodium citrate dihydrate 1.478%, pH 4.5), 1.3 mg / ml p-nitrophenyl-N-acetyl-bD-glucosaminide] and 37 After reacting at 1 ° C. for 1 hour, the reaction was stopped with 0.2 M glycine (pH 10.7), and the absorbance was measured at 405 nm using ELISA, and the measured value was converted into% release granules. Is shown in FIG. 3.

As a result, as shown in FIG. 3, the concentration required for 50% inhibition in the β-HEX (β-Hexosaminidase) free inhibition experiment was 22.4 ㎍ / ml, indicating a strong inhibitory activity.

Experimental Example  4. Terms in Animal Models allergy  Inhibitory effect

In order to determine the anti-allergic capacity of the in vivo (70%) ethanol fraction obtained in Example 1-2, the experiment was described as follows using the method described in the literature. Lin et al., Planta Medica , 70 (5) , pp. 474-476, 2004)

Passive cutaenous anaphylaxis (Katayama S, Shionoya H and Ohtake) for rats, a typical type I allergy model, using male Sprague-Dawley rats (Hyochang Science). S, Microbiol Immunol 22: 89-101, (1978).

    Monoclonal anti DNP mouse IgE (Sigma, Inc., 100 μl, 1000-fold diluted solution) was administered to Sprague-Dawley rats 48 hours prior, followed by antigen (DNP, Sigma) 1 Hours ago, 25-100 mg / kg / 100 μl of ethanol fraction (dissolved in 0.5% CMC) was orally administered, with 1-10 mg / kg / 100 μl of dexamethasone (Sigma) as a positive control. Then, 1 mg DNP-BSA (antigen solution) / 1% Evans blue solution was injected into the tail vein, and after 30 minutes the pigment spilled on the skin was measured, and the result is shown in FIG. It was.

    As a result, as shown in Figure 4, it was confirmed that the substance of the present invention exhibits significant anti-allergic action in the allergy model in vivo.

      Hereinafter, the preparation examples of the composition including the extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail only.

Formulation example  1. Preparation of Injection

70% Ethanol Soluble Extract of Sweet Ginseng 100 mg

Sodium Metabisulfite 3.0 mg

Methylparaben 0.8 mg

Propylparaben 0.1 mg

Appropriate sterile distilled water for injection

        The above ingredients are mixed and prepared in a conventional manner to have a final volume of 2 ml, and then filled into 2 ml ampoules and sterilized to prepare an injection.

Formulation example  2. Pilled  Produce

120% 70% Ethanol Soluble Extract of Salvia

Corn Starch 100mg

Sterile distilled water

       The above components are mixed and refilled in a 0.3 cm diameter by a conventional pill manufacturing method to prepare pills.

Formulation example  3. Preparation of Tablets

70% Ethanol Soluble Extract of Salviae Radix 200 mg

Lactose 100 mg

Starch 100 mg

Magnesium stearate proper amount

       A tablet is prepared by mixing and tableting the above components according to a conventional tablet manufacturing method.

Formulation example  4. Preparation of Capsules

70% Ethanol Soluble Extract of Sweet Ginseng 100 mg

Lactose 50 mg

Starch 50 mg

Talc 2 mg

Magnesium stearate appropriate amount

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

Formulation example  5. Liquid  Produce

Soybean 70% Ethanol Soluble Extract 1000mg

20 g of sugar

20 g of isomerized sugar

Lemon flavor

     Purified water was added to make a total of 1000 ml. According to the conventional method for preparing a liquid, the above components are mixed, and then filled into a brown bottle and sterilized to prepare a liquid.

Formulation example  6. Manufacture of healthy food

Soybean 70% Ethanol Soluble 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 food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. 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

Soybean 70% Ethanol Soluble 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 in accordance with a 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 in the present invention For the preparation of healthy beverage compositions.

As described above, the crude extract, polar solvent soluble extract or nonpolar solvent soluble extract of the present invention is the production of leukotriene C ₄ (leukotriene C ₄ , LTC ₄ ) dependent on lipoxygenase (5-LOX, 5-lipoxygenase) Inhibition, inhibition of production of prostaglandin D ₂ (PGD ₂ ) dependent on cyclooxygenase-2 (COX-2, cyclooxygenase-2), as well as degranulation reaction inhibition in mast cells, resulting in asthma and It can be usefully used as a composition for the prevention and treatment of allergic diseases.

Claims (7)

Pharmaceutical composition for the prevention and treatment of asthma and allergic diseases containing crude extract, polar solvent soluble extract or non-polar solvent soluble extract of salvia as an active ingredient. The pharmaceutical composition according to claim 1, wherein the crude extract is an extract available in 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 polar solvent soluble extract is an extract soluble in a solvent selected from water, methanol, ethanol, butanol, or a mixed solvent thereof. The pharmaceutical composition according to claim 1, wherein the nonpolar solvent soluble extract is an extract soluble in a solvent selected from hexane, chloroform and ethyl acetate. The pharmaceutical composition of claim 1, wherein the allergic disease is bronchial asthma, allergic rhinitis, allergic asthma and allergic dermatitis. Health functional food for the prevention and improvement of asthma and allergic diseases containing crude extract, polar solvent soluble extract or non-polar solvent soluble extract of salvia as an active ingredient. 7. The dietary supplement of claim 6 which is a powder, granule, tablet, capsule or beverage.

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