KR100750873B1 - A pharmaceutical composition comprising the extract of Rubiae Radix for treating or preventing allergic disease - Google Patents

Abstract

The present invention relates to a medicinal composition for the prevention and treatment of cheoncho root extract and allergic diseases including the extract, more specifically, the cheoncho root extract according to the present invention has the effect of inhibiting the secretion of allergens from mast cells Therefore, the composition comprising the myelin extract according to the present invention by treating the root cause in the conventional approach to alleviate the symptoms of allergy treatment, not only has an excellent antiallergic effect, but also prevention of allergic diseases without toxicity and side effects and It can be usefully used as a medicine or health food for treatment.

Cheoncho Geun, Antiallergic, Mast Cell, Medicine, Health Food

Description

A pharmaceutical composition comprising the extract of Rubiae Radix for treating or preventing allergic disease

Figure 1 shows the concentration-dependent inhibitory effect of cheoncho root extract according to the present invention on allergen-induced mast cells (RBL 2H3),

Figure 2 shows the inhibitory effect of cheoncho muscle extract according to the present invention when stimulating allergens of mast cells (RBL 2H3) with other substances.

The present invention relates to a pharmaceutical composition for the prevention and treatment of cheoncho root extract and allergic diseases including the extract.

      Mast cells and blood basophils are known to be cells in the body causing various allergic diseases, such as allergic rhinitis, allergic dermatitis, asthma, food allergy and anaphylactic shock. These cells have receptors for IgE (FcεRI), an allergic antibody on the cell surface, which are stimulated by allergens (called antigens or allergens) to cause various allergies they have. Secrete the substance out of the cell.

      There are many ways to treat allergies, but most modern allergy treatments are being studied to alleviate the symptoms rather than eliminate the cause. Representatively, antagonists of histamine and leukotriene, which are secreted by mast cells from allergens, are dominant and these drugs form a huge market. However, since these drugs are resistant to patients within a short period of time after administration, they often do not improve symptoms after a certain period of time or repeated administration. Therefore, the present invention was intended to develop an allergy treatment without side effects such as antihistamines occurring in patients by blocking allergen secretion in mast cells and the like.

      In addition to other treatments, allergens for allergy sufferers to identify allergies and then administered in small amounts for several years there is a way to gradually reduce the allergy. This method, however, has the disadvantage that treatment takes several years and can cause anaphylactic shock. Therapeutic approaches include the use of other DNA vaccines, therapies that block IgE from binding to mast cell receptors, and the treatment of antibodies to IL4, an allergic cytokine. However, these approaches are expensive or have not yet been fully elucidated.

Cheoncho Geun ( Rubia radix ) is a folk name, also known as marionette , has long been known to have various pharmacological effects. In oriental medicine, blood circulation is smoothed to remove fish blood and hemostasis is known, and joints are used to control pain and pain. In addition, recently, cardiac action, hemostatic action, uterine contraction action, diuretic action, antibacterial action and the like have been reported.

However, no disclosure or teaching has been made about the antiallergic effect on the extract.

      Accordingly, the present inventors block the secretion of allergens from mast cells that cause discomfort to humans such as allergic rhinitis and asthma or cause various fatal allergens. As a result of intensive efforts to secure from the result, the present invention was completed by confirming that the extract of Cheoncho Geun according to the present invention inhibits the secretion of allergens from mast cells in addition to the herbal pharmacological theory.

After all, the main object of the present invention is to provide a cheoncho root extract having an antiallergic effect by blocking the secretion of allergens secreted from mast cells causing various allergic or fatal allergic rhinitis, asthma, etc. .

In addition, another object of the present invention to provide a pharmaceutical composition for the prevention and treatment of allergic diseases comprising the cheoncho root extract.

It is another object of the present invention to provide a method for producing a cheoncho root extract having an antiallergic effect.

In order to achieve the above object, the present invention provides a bark extract showing an antiallergic effect by blocking the secretion of allergens.

Chuncho root extract according to the present invention includes water and C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol and the like, and a mixed solvent thereof, preferably extracts soluble in ethanol.

The present invention also comprises the steps of (a) washing the cheoncho root with distilled water and pulverizing with a grinder; (b) heating the pulverized cheoncho root in boiling water to obtain a cheoncho root extract; (c) filtrating the supernatant extract to obtain a supernatant and concentrating; And (d) freezing-drying the cheoncho root concentrate to obtain a concentrate powder, thereby providing a method for producing a cheoncho root extract that exhibits an antiallergic effect by blocking the secretion of allergens.

In the present invention, the water in the step (a) may be characterized in that 1 L per 100 g of the cheoncho root raw material is added, and in the step (b) the cheoncho root in the boiling water of 100 ~ 120 ℃ 2-3 It may be characterized in that the extraction by heating for a time.

The present invention also comprises the steps of: (a) dipping the myelin root in lower alcohol to extract with an ultrasonic extractor to obtain an alcohol extract; (b) filtering the supernatant of the alcohol extract and then concentrating; And (c) freezing-drying the cheoncho root concentrate to obtain a concentrate powder, thereby providing a method for producing a cheoncho root extract that exhibits an antiallergic effect by blocking the secretion of allergens.

In the present invention, the cheoncho root may be characterized in that the subterranean portion of cheoncho root cultivated in natural or artificial, the lower alcohol in step (a) may be characterized in that 95% ethanol, the step (a ) May be characterized by extracting for 2-4 weeks.

Hereinafter, the present invention will be described in detail.

Cheoncho root extract according to the present invention can be obtained as follows.

After collecting, drying and pulverizing the cheoncho root of the present invention, the volume of water and methanol, ethanol, butanol and the like of about 2 to 20 times, preferably about 5 to 10 times the weight of the sample A polar solvent of the same C ₁ to C ₄ lower alcohols or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably hot water extraction, cold extraction, reflux cooling extraction or ultrasonic extraction with water or ethanol The supernatant is recovered by vacuum filtration using an extraction method such as the above, and the above procedure is repeated several times to collect the supernatant, and concentrated under reduced pressure to obtain the cheoncho root extract.

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

In addition, cheoncho root has been used as a herbal medicine for a long time, the extract according to the present invention extracted therefrom also does not have problems such as toxicity and side effects.

The pharmaceutical composition for preventing and treating allergic diseases according to the present invention comprises 0.1 to 50% by weight of the extract based on the total weight of the composition.

The pharmaceutical composition comprising the extract of the present invention may further comprise suitable tints, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.

Pharmaceutical compositions comprising extracts according to the invention, 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. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, aceitol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyrrolidone, 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 such solid preparations may contain at least one excipient such as starch, calcium carbonate and sucrose in the extract. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, 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 oils such as olive oil, injectable esters 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 preferred effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The present invention provides a health functional food comprising the extract and a food acceptable food supplement additive exhibiting a prophylactic effect of allergic diseases.

Examples of the food to which Cheoncho-geun extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

It may also be added to foods or beverages for the purpose of preventing allergic diseases. At this time, the amount of the extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml. have.

The health functional beverage composition of the present invention is not particularly limited to other ingredients in addition to containing the extract as an essential ingredient in the indicated ratio, and may contain additional ingredients such as various flavoring agents or natural carbohydrates as in general beverages. . 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 a flavoring agent other than the above-mentioned, a natural flavoring agent, taumartin, a stevia extract, for example, rebaudioside A, glycyrrhizin, etc .; And synthetic flavoring agents such as saccharin, aspartame and the like. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above, the extract of the present invention has various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective properties Colloidal 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 flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. At this time, the ratio of the additive is not very important, but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

Hereinafter, the present invention will be described in more detail based on the following Examples and Experimental Examples. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.

Example 1: Preparation of Cheoncho Geun Extract

(1) boiling water extraction method

100 g of cheoncho root was washed with distilled water and finely pulverized by a pulverizer, and then extracted by heating for 2 to 3 hours in a boiling water at 100-120 ° C. while reflux cooling by adding 1.0 L of water. Filtration recovered the supernatant. The recovered supernatant was concentrated using a concentrator, and the cheoncho root concentrate was lyophilized at -80 ° C to prepare a concentrate powder of cheoncho root extract.

(2) Organic Solvent Extraction Method

Cheoncho root was immersed in 95% ethanol and extracted for 2 to 3 weeks using an ultrasonic extractor to obtain an alcohol extract. Then, only the supernatant was separated and filtered to remove foreign substances. The alcohol extract obtained above was concentrated using a concentrator, and then lyophilized at -80 ° C to prepare a concentrate powder of cheoncho root extract.

Experimental Example 1: Confirmation of the inhibitory effect of allergens on mast cells

In order to investigate the inhibitory effect of allergen-producing substances from the Chunchogeun extract extracted from Example 1 allergenic cells in the body, RBL-2H3 cells in a minimal medium supplemented with glutamine, antibiotics and 15% bovine serum Incubated.

After the cells were harvested by trypsin for secretion experiments, 200,000 cells per well were incubated with 25 ng / ml DNP-specific IgE in a 24-well incubator. The cultured cells were washed with PIPES buffer (25 mM PIPES, pH 7.2, 159 mM NaCl, 5 mM KCl, 0.4 mM MgCl ₂ , 1 mM CaCl ₂ , 5.6 mM glucose, and 0.1% BSA) and then the antigen was added. Pre-incubation for 30 minutes before. After preculture, the antigen was added at a final concentration of 25 ng / ml to induce stimulation.

The secretion of allergens was determined by the amount of p-nitrophenol liberated from p-nitrophenyl-acetyl-β-D-glucosaminide, a marker of degranulation.

(1) the secretion of allergens from mast cells by antigen Supernatural  Inhibitory effect

1 shows allergen-induced mast cell RBL-2H3 (Funaba, M. et al., Cell Biol. Int., 27: 879-85, 2003; Jeong, HJ et al., Cytokine, 18: 252-9, It was shown that the concentration-dependent inhibitory effect of the cheoncho root extract according to the present invention for 2002), the cheoncho root extract according to the present invention concentration-dependently inhibit the secretion of various allergens of mast cells. The concentration of the extract of S. aeruginosa (IC ₅₀ ), which inhibits 50% of its highest secretion, was about 34 μg / ml, indicating a high inhibitory effect at relatively low concentrations, and more than 80% of the secretion was suppressed at 100 μg / ml.

(2) Inhibitory Effect of Cheoncho-Geun on Secretion of Allergens from Mast Cells by Compound 48/80

Figure 2 shows the inhibitory effect of the extract according to the present invention when stimulating allergens of mast cells RBL-2H3 with other substances (compound 48/80). As shown in Figure 2, the secretion of allergens from mast cells by the compound 48/80 was also significantly inhibited at low concentrations (IC ₅₀ ; about 23.6 ㎍ / ㎖) by cheoncho root extract, secreted at 100 ㎍ / ㎖ Was suppressed more than 80%.

From this, the cheoncho root extract of the present invention was confirmed to exhibit an allergic inhibitory effect by blocking all the various secretion pathways of mast cells.

Example 3: Confirmation of antiallergic effect in allergic animal model

Systemic allergic reactive anaphylactic shock animal models were obtained by intraperitoneally administering compound 48/80 to mice at 8 mg / kg. One hour before the 48/80 compound administration, the extract was administered to confirm the anaphylactic shock inhibitory effect, the results are summarized in Table 1.

As shown in Table 1, the cheonchogeun extract was inhibited the reaction, 42.8% was suppressed in the 100 mg / kg administration group, 48.5% was inhibited in the 300 mg / kg administration group. From this, it was confirmed that the cheoncho root extract of the present invention exhibits the effect of suppressing high allergic diseases not only in vitro but also in disease animal models.

Table 1 Protective Effect of Cheoncho-Geun Extract on Systemic Anaphylactic Shock Induced by Compound 48/80

Dose (mg / kg) Compound 48/80 (8 mg / kg) Survival rate (%)  0  + 0.0  30  + 28.5  100  + 42.8  300  + 48.5  300  - 100.0

The specific parts of the present invention have been described in detail above, and it is apparent to those skilled in the art that such specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. something to do. Thus, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

One example of the formulation of the pharmaceutical composition comprising the extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail.

Formulation Example 1 Preparation of Powder

Cheoncho Geun Extract Powder 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

Cheoncho Geun Extract Powder 10mg

100 mg corn starch

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

Cheoncho Geun Extract Powder 10mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 2mg

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

Cheoncho Geun Extract Powder 10mg

Mannitol 180 mg

Sterile distilled water for injection 2794 mg

_{Na 2 HPO 4 · 12H 2 O} 26 ㎎

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

Cheoncho Geun Extract Powder 10mg

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 appropriate amount, the above components are mixed, and then purified water is added to adjust the total amount to 100 ml, and then sterilized by filling in a brown bottle. To prepare.

Formulation Example 6 Preparation of Healthy Drink

Cheoncho Geun Extract Powder 10mg

15 g of vitamin C

100 g of vitamin E (powder)

Iron lactate 19.75 g

3.5 g of zinc oxide

Nicotinamide 3.5 g

0.2 g of vitamin A

0.25 g of vitamin B1

0.3 g of vitamin B2

Water

After mixing the above components according to a conventional healthy beverage production method, and then 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 refrigerated and stored in the present invention It is used to prepare a healthy beverage composition according to.

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

As described above, the cheoncho root extract according to the present invention exhibits an antiallergic effect of allergy-inducing alleviating allergic symptoms by inhibiting allergen-induced secretion of mast cells and inducing allergy at low concentrations in animal models of allergy. It can be used as a pharmaceutical composition or health functional food for the prevention and treatment of diseases.

In addition, unlike the conventional symptom recovery-oriented treatment, it is expected that it can be usefully used as a pharmaceutical composition or health functional food that can remove various side effects by blocking the secretion of allergens in mast cells.

Claims (11)

delete delete delete delete delete delete delete delete A pharmaceutical composition for the prevention and treatment of allergic diseases containing the extract of Cheoncho Geun as an active ingredient. Health functional food for the prevention and improvement of allergic diseases including Cheoncho Geun extract and food acceptable food supplement additives The dietary supplement of claim 10 which is a health beverage.

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