KR20110085517A - Pharmaceutical composition for preventing and treating allergic diseases comprising anthraquinone derivatives - Google Patents

Abstract

PURPOSE: A pharmaceutical composition containing anthraquinone derivative for preventing and treating allergic diseases is provided to suppress prostaglandin D2 generation. CONSTITUTION: A pharmaceutical composition for preventing and treating allergic diseases contains anthraquinone derivative of chemical formula 1 as an active ingredient. The anthraquinone derivative is emodin, citreorosein, emodin-8-beta-D-glucoside, physcion, or chrysophanol. A health food for treating allergic diseases contains the anthraquinone derivative of chemical formula 1 as an active ingredient. The health food is powder, granule, tablet, capsule, syrup, or beverage.

Description

Pharmaceutical composition for preventing and treating allergic diseases comprising anthraquinone derivatives}

The present invention relates to a pharmaceutical composition for preventing and treating allergic diseases, which contains an anthraquinone derivative effective as an active ingredient for the prevention and treatment of allergic diseases including asthma.

In general, allergy is a symptom of a hyperimmune reaction, and symptoms such as gastrointestinal allergy, gall margin, atrophic dermatitis, allergic rhinitis and asthma.

Among them, asthma is a 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. Get involved.

Substances involved in asthma are inflammatory, other than leukotriene (LT), C ₄ , D ₄ , and E ₄ , a metabolite of 5-lipoxygenase, known as the slow reacting substance of anaphylaxis (SRS-A). It is known that cytokines such as Interleukin (IL) -4, -5, -6 are involved (Barnes P. J, et al., Inflammatory mediators of asthma: an update, Pharmacol Rev, 50, pp 515-596, 1998; Galli S, et al., Mast-cell-leukocyte cytokine cascades in allergic inflammation, Allergy 50, pp 851-862, 1995).

Key mediators that induce allergic diseases such as asthma, prostaglandins, acids (prostaglandines), leukotriene acids (leukotriens), platelet activating factor (PAF) Phospholipase A ₂ (phospholipase A _2), such as, cyclooxygenase (cyclooxygenase ) And lipoxygenase to generate from the precursor arachidonic acid.

Prostaglandins bind to specific cell surface receptors and act to increase the intracellular concentration of cAMP (and in some cases cGMP). The effect of increasing cAMP depends on cell type and PGA ₂ , PGB _{2 lower} blood pressure (Cicardo VH, Mechanism of the hypotensive effect of prostaglandins A2 and E2, Acta. Physiol. Lat. Am, 1981; 31, pp 85-91, 1981; Liu F, et al., Prostaglandin B2-induced pulmonary hypertension is mediated by TxA2 / PGH2 receptor stimulation.Am. J. Physiol, 267, pp 602-608, 1994), PGD ₂ , PGE ₁ (Gollman HM et al., Comparative pyrogenic potency of endogenous prostanoids and of prostanoid-mimetics injected into the anterior hypothalamic / preoptic region of the cat.Brain Res. 449, pp281-293 , 1988, Collins DR, et al., Cutaneous sympathetic motor rhythms during a fever-like response induced by prostaglandin E (1), Neuroscience, 110, pp 351-360, 2002).

In particular, PGD ₂ is known to exacerbate asthma by contracting smooth muscle in bronchial asthma patients (Shiraishi Y, et al., Cyclooxygenase-2 / prostaglandin D2 / CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation, J. Immunol., 180, pp 541-549, 2008). Leukotriens (LT) constitute a group of locally acting hormones produced in vivo from arachidonic acid. Important leukotrienes include leukotriene B ₄ (LTB ₄ ), leukotriene C ₄ (LTC ₄ ), and leukotriene D ₄ (LTD). ₄ ) and leukotriene E4 (LTE ₄ ). Biosynthesis of these leukotrienes begins by the action of enzyme 5-lipoxygenase on arachidonic acid to produce an epoxide known as leukotriene A _4, which is produced by successive enzymatic reaction steps (LTB ₄ , LTC ₄ , LTD _4). , LTE ₄ ). Leukotriene is known to be involved in allergic and allergic reactions such as pulmonary artery disease such as asthma, chronic bronchitis and associated obstructive airway disease, allergic rhinitis, contact dermatitis, allergic conjunctivitis and the like.

Recently, drugs that have attracted attention as an allergic asthma treatment are drugs that have both histamine free inhibition, leukotriene C ₄ production inhibition, and platelet activator inhibitory activity (Dahlen SE, Treatment of asthma with antileukotrienes: first line or last resort therapy). , Eur. J. Pharmacol., 533, pp 40-56, 2006; Kitamura S, Leukotriene (B4, C4, D4, E4), Nippon Rinsho., Suppl 8, pp28-33, 2005).

However, the treatment and prevention of such diseases are still emerging as one of the important tasks of the medical community, but the fundamental treatment is not achieved, and only the conventional treatment is performed, and the development of fundamental treatments and treatments is urgently needed.

Thus, the inventors have found that the anthraquinone derivatives inhibit cyclooxygenase-2 dependent prostaglandin D ₂ production, which is involved in allergic reactions, inhibit 5-lipoxygenase dependent leukotriene C ₄ production, and at the same time from mast cells. Inhibition of degranulation and inhibition of the production of tumor necrosis factor-α, interleukin-6 and interleukin-1β in mast cells induced by PMA / A23187, particularly in allergic animal models induced by IgE / antigen The present invention has been completed by demonstrating an allergic effect.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing and treating allergic diseases and health foods for improving allergic diseases by examining the antiallergic effect of anthraquinone derivatives.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating allergic diseases containing an anthraquinone derivative represented by the following formula (1) as an active ingredient:

[Formula 1]

In Formula 1, R ¹ and R ² are each selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, C1 to C4 alcohol, or hydroxy, and R ³ is a monosaccharide.

The pharmaceutical composition according to the present invention preferably contains 0.1 to 50 parts by weight of anthraquinone derivatives based on 100 parts by weight of the total pharmaceutical composition. If the anthraquinone derivative is contained in a small amount out of the above content range, it is difficult to obtain the desired antiallergic activity, and if it is contained in an excessive amount, the treatment and prevention effect of allergic diseases will be slowed down compared to the dose, and may cause side effects. Uneconomic problems can arise.

The anthraquinone derivative is any ^one of R ¹ and R ² are selected from hydrogen, methyl, methoxy, methanol, hydroxy, and R ³ may be glucose, more preferably the anthraquinone derivative is an emodine, a sheet. It may be any one selected from leurosene, emodin-8-O-β-D-glucoside, fishion or chrysopanol.

Anthraquinone derivatives according to the present invention are tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL) in mast cells. -1 beta) and the like can inhibit the production of inflammatory cytokines, and degranulation reaction from mast cells.

More specifically, the anthraquinone derivatives according to the present invention are cyclooxygenase-2 (COX-2) dependent prostaglandin D ₂ (Prostaglandin D ₂ , PGD ₂ ) involved in allergic and asthmatic reactions. Leukotriene C ₄ (LTC ₄ ), which inhibits production and is 5-lipoxygenase (5-LOX) dependent Inhibition of production and at the same time inhibited the degranulation reaction from mast cells. Inhibition of inflammatory cytokines such as TNF-α, IL-6 and IL-1β was inhibited in mast cells induced by PMA / A23187. In addition, allergic animal models induced by IgE / antigen also showed antiallergic activity.

The allergic disease may be any one selected from the group consisting of asthma, hypersensitivity, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, contact dermatitis and urticaria.

In addition, the pharmaceutical composition according to the present invention may further include a suitable carrier, excipient or diluent commonly used in the preparation of the pharmaceutical composition.

Carriers, excipients or diluents usable in 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, mineral oil, and the like.

The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method .

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, and the solid form preparations include at least one excipient such as starch, calcium carbonate, sucrose ( Prepare by mixing sucrose or lactose, gelatin, etc.

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.

In particular, the pharmaceutical composition according to the present invention is more preferably used as an oral inhalation or intranasal administration formulation. Formulations for oral inhalation administration may be administered as liquid or powder compositions using metered dose inhalers (MDIs), dry powder inhalers (DPIs), jet-nebulizers, ultrasonic nebulizers, and the like. have. In addition, the formulation for intranasal administration can be administered as a liquid or powder composition using a pressurized metering sprayer, a dry powder sprayer, a dropping vessel, or the like.

The amount of the anthraquinone derivative, which is an active ingredient of the pharmaceutical composition according to the present invention, may vary depending on the age, sex, and weight of the patient, but is preferably 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg once or several times daily. May be administered.

In addition, the dosage of the anthraquinone derivative may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

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, intrabronchial inhalation, intrauterine dural or intracerebroventricular injection.

The anthraquinone derivative is a safe substance derived from natural medicinal herbaceous ginseng, and in particular, 50% lethal dose (LC50) is 2 g / kg or more, and ensures stability, and may be used in the pharmaceutical composition of the present invention.

In addition, the present invention provides a health food for improving allergic diseases containing an anthraquinone derivative represented by the following formula (1) as an active ingredient:

[Formula 1]

In Formula 1, R ¹ and R ² are each selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, C1 to C4 alcohol, or hydroxy, and R ³ is a monosaccharide.

The health food may be provided in the form of powder, granules, tablets, capsules, syrups or beverages.

The health food is used with other foods or food additives in addition to the anthraquinone derivatives, and may be suitably used according to conventional methods. The mixed amount of the active ingredient may be appropriately determined depending on the purpose of use thereof, for example, prophylactic, health or therapeutic treatment.

An effective dose of the anthraquinone derivative contained in the health food may be used according to the effective dose of the pharmaceutical composition, but may be less than the above range for long term intake for health and hygiene purposes or health control purposes. Since the active ingredient has no problem in terms of safety, it is evident that the active ingredient can be used in an amount above the above range.

There is no particular limitation on the kind of the health food, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, drinks, tea, Drinks, alcoholic drinks, vitamin complexes, etc. are mentioned.

Anthraquinone derivatives according to the present invention inhibit the production of cyclooxygenase-2 (COX-2) dependent prostaglandin D ₂ (PGD ₂ ), which is involved in allergic and asthmatic reactions, and 5-lipoxygenase (5- LOX) dependent leukotriene C ₄ (LTC ₄ ) Inhibits production and at the same time inhibits degranulation from mast cells, as well as the production of inflammatory cytokine production such as TNF-α, IL-6 and IL-1β (IL-1β) in PMA / A23187-induced mast cells It can also be suppressed. In particular, IgE / antigen-induced allergic animal models exhibit anti-allergic activity and can be usefully used for the prevention and treatment of allergic diseases including asthma.

Figures 1a and 1b is to examine the effects of inhibiting COX-2 dependent PGD ₂ production and COX-2 protein expression according to the emodin treatment,
Figure 2 examines the effects of 5-LOX dependent LTC ₄ production following emodin treatment,
Figure 3 examines the effect of inhibiting mast cell degranulation according to the emodin treatment,
Figure 4 examines the effect of inhibiting allergic reactions in vivo according to the emodin treatment,
5 to 7 examine the effects of inhibiting the production of TNF-α, IL-6 and IL-1β, respectively.

Hereinafter, the present invention will be described in more detail with reference to the following Examples and Experimental Examples. However, these examples and the like are merely illustrative of the present invention, the contents of the present invention is not limited to these examples and the like.

Example 1 Preparation of Anthraquinone Derivatives

Anthraquinone derivatives emodin, citreosein, fishion, emodin-8-O-β-D-glucoside were isolated from the roots of Reynoutria japonica , and chrysopanol was purchased from ChromaDex (USA). Was used.

Reference Example 1 Experimental Cell Culture

Mouse bone marrow-derived mast cells (BMMC) were isolated from bone marrow from BALB / C mice, and RPMI-1640 medium containing 10% FBS, 100 U / ml penicillin, 100 μg / ml streptomycin and IL Incubation was performed for about 3 weeks with -3 (culture of supernatant obtained by stimulation with pokeweed mitogen to spleen cells of mouse to the final 20%) to obtain more than 95% homogeneous BMMC.

Experimental Example 1 COX-2 Dependent Prostaglandin D ₂  Review of generation inhibitory effects

In order to confirm the degree of inhibition of allergic and asthma diseases of the anthraquinone derivatives prepared in the above example, prostaglandin D ₂ (PGD) was performed using prostaglandin D ₂ EIA kit (Cayman, PGD2-MOX EIA kit, product no. 512011). The production amount of ₂ ) was measured.

After 3 weeks of culture of mouse bone marrow-derived mast cells (BMMC) prepared according to Reference Example 1, the anthraquinone derivatives (final concentration 20 μM) prepared in the above example were pretreated for 30 minutes at a cell concentration of 2 × 10 ⁵ cells / well. After treatment with IgE / Ag, the prostaglandin D ₂ in the supernatant was measured by EIA (Enzyme linked immunoassay) using a prostaglandin D ₂ assay kit (Cayman) after 8 hours of cell stimulation. At this time, in order to inhibit the production of prostaglandin D ₂ produced by COX-1, 10 μg / ml of aspirin was pretreated with mouse bone marrow-derived mast cells 1 hour beforehand.

After washing 4 times with a washing buffer, the substrate solution was treated with 200 µl of each solution for 5-20 minutes, and then treated with 50 µl of stop solution, and then absorbed at 450 nm. Was measured by ELx800 (BIO-TEK, Instrument, Inc, USA). The antibody used as a stimulant may include IgE [Monoclonal anti-dinitrophenyl (DNP); Sigma, D8406] and DNP-HSA (Sigma, A6661) were used as the antigen (Ag).

As a result, as shown in Table 1, anthracene derivatives including emodine, citreosein, and chrysopanol showed excellent COX-2 dependent prostaglandin D ₂ production inhibitory effect. In particular, as shown in FIG. 1A, emodine inhibited COX-2 dependent prostaglandin D ₂ production in a concentration-dependent manner.

Experimental Example 2 Examination of COX-2 Protein Expression Inhibition Effect

Lysis buffer (lysis buffer; 20mM Tris, 137mM NaCl, 5mM Na ₂ EDTA, 10% Glycerol, 1% Triton X-100, 1m in BMMC incubated in a 24-well plate at a concentration of 1 × 10 ⁶ cells / well) MEGTA, 10mM NaF, 1mM PMSF, 1mM Na ₃ VO ₄ ) were added and placed on ice for 30 minutes (shaking every 5 minutes), followed by centrifugation to obtain a supernatant.

Proteins of the whole cells were electrophoresed by SDS-PAGE and electrophoresed to natrocellulose paper using a buffer containing 20% methanol, 25 mM Tris (pH 7.4), 192 mM glycine. Membrane from which proteins were transferred was checked for migration with Ponceau solution, and then blocked with 5% skim milk solution at room temperature for 30 minutes. The membrane was reacted with COX-2 antibody (1: 1000 dilution, Cell Signaling Technology, Inc. Danvers, MA, USA) diluted with TTBS (0.05 M Tris, 0.75 M NaCI, 0.25% Tween 20) buffer for at least 12 hours. . After the reaction was washed three times with TTBS.

Again the reaction with horseradish peroxidase attached secondary antibody (Cell Signaling Technology, Inc. Danvers, MA, USA) for 2 hours and washed three times with TTBS. After washing, wash with distilled water, react with chemiluminesence (ECL) system (Amersham Biosciences, Piscataway, NJ, USA) solution for 2 minutes, and compare the thickness of the bands on the film. Confirmed.

As a result, as shown in FIG. 1B, emodine inhibited COX-2 protein expression in a concentration-dependent manner.

<Experiment 3> Examination of the inhibitory effect of leukotriene production

In order to confirm the effect on the leukotriene C ₄ production of the anthraquinone derivatives prepared in the above examples, experiments were carried out by applying the method disclosed in the literature (Chang HW et al. Planta. Medica., 70 (5), pp. 474-476, 2004).

After 3 weeks of culture of mouse bone marrow-derived mast cells prepared in Reference Example 1, the anthraquinone derivatives prepared in Example were added to mast cells (2 × 10 ⁵ cells / well) at a constant concentration (2.5, 5, 10, 20 μM). After pre-treatment for 30 minutes, it was treated with IgE / Ag. After 10 minutes of cell stimulation, leukotriene C ₄ quantification of the supernatant was measured using a leukotriene C ₄ EIA kit (Enzyme linked immunoassay, Cayman, product no. 520211). The antibody used as a stimulant may include IgE [Monoclonal anti-dinitrophenyl (DNP); Sigma, D8406] and DNP-HSA (Sigma, A6661) were used as the antigen (Ag).

As a result, as shown in Table 1, anthracene derivatives including emodin, citreosein, and chrysophanol showed excellent leukotriene C ₄ production inhibitory effect. In particular, as shown in FIG. 2, emodin inhibited the production of leukotriene C ₄ in a concentration-dependent manner.

Experimental Example 4 Inhibition of Mast Cell Degranulation Response

Mouse bone marrow-derived mast cells (BMMC) prepared in Reference Example 1 were treated with a concentration of prepared anthraquinone derivatives at a concentration of 2Ｘ10 ⁵ cells / ml for 30 minutes at 37 ° C. and 5% CO ₂ conditions for preincubation. After stimulation with IgE / Ag, the cells were incubated for 15 minutes and centrifuged at 3000 rpm for 4 minutes at 4 ° C.

The supernatant was beta-hexosaminidase (β-HEX) [100 mM citric acid buffer solution (0.955% citric acid, 1.478% sodium citrate dihydrate, pH 4.5), 1.3 mg / ml p-nitrophenyl-N -Acetyl-bD-glucosaminide] 1: 2 and reacted for 1 hour at 37 ℃, the reaction was stopped with 0.2M glycine (pH 10.7) to measure the absorbance at 405nm wavelength using ELISA The measured value was converted into% release granules. The antibody used as a stimulant may include IgE [Monoclonal anti-dinitrophenyl (DNP); Sigma, D8406] and DNP-HSA (Sigma, A6661) were used as the antigen (Ag).

[Equation 1]

% Degranulation = [free β-hex activity in culture supernatant / (released β-hex activity in culture supernatant + intracellular β-hex activity)] X 100

As a result, as shown in Table 1, anthracene derivatives including emodine and citreosein showed excellent β-hex free inhibitory effect. In particular, as shown in FIG. 3, emodine inhibited β-hex release in a concentration-dependent manner.

compound
(Final concentration 20 μM) PGD ₂  Production Inhibition (%) LTC ₄  Production Inhibition (%) β-hexosminidayes glass inhibition (%) Emodin 99.9 99.9 100 Citreosepine 99.9 99.9 99.2 Fish 59.6 59.6 68.1 Emodine-8-O-β-D-glycoside 46.1 23.5 35.2 Chrysopanol 99.9 99.9 72.8

Experimental Example 5 Examination of Anti-allergic Effect in Animal Model

In order to confirm the anti-allergic effect of the emodin prepared in Example in vivo (in vivo), the experiment was carried out by applying the passive cutaneous anaphylaxis method disclosed in the literature as follows: (Katayama S, Shionoya H and Ohtake S, Microbiol Immunol, 22, pp.89-101, 1978).

Mice (ICR mouse, ordered from SAMTACO BIO KOREA) were diluted 1000-fold with monoclonal anti-DNP mouse IgE (Sigma) and administered 100 μl before 24 hours, followed by antigen (DNP, Sigma) administration for 30 minutes. Emodine previously dissolved in CMC (Carboxymethylcellulose) was orally administered 50 mg / kg / 100 μl 1 hour prior to antigen administration.

Then 1 mg DNP-BSA (antigen solution) / 1% Evans blue solution was injected into the tail vein. After 30 minutes, the pigment spilled on the skin was measured. As a control, only 50 mg / kg / 100 μl of CMC (Carboxymethylcellulose) was orally administered.

As a result, as shown in Figure 4, emodin showed an allergic reaction inhibitory effect of about 48% in the allergy animal model in vivo.

Experimental Example 6 Inhibition of Inflammatory Cytokine Production

Mouse bone marrow-derived mast cells (BMMC) prepared in Reference Example 1 were treated with ₂ ° 10 ⁵ cells / ml of a predetermined concentration of emodine, followed by preincubation for 1 hour under 37 ° C. and 5% CO _2. TNF-α (tumor necrosis factor-α) production was stimulated with phorbol 12-myristate 13-acetate, Sigma) / A23187 (Calcium Ionophore A23187) for 6 hours, for 3 hours for IL-6, and for IL-1β. In the case of incubation for 24 hours and centrifuged for 5 minutes at 3000rpm, 4 ℃. Supernatants were measured using an EIA kit. In this case, PDTC (pyrrolidine dithiocarbamate, Sigma), an NF-κB pathway inhibitor, was used. In addition, all products of R & D systems (USA) were used to measure the production of TNF-α, IL-6 and IL-1β.

As a result, as shown in FIGS. 5 to 7, emodin inhibited the production of inflammatory cytokines TNF-α, IL-6, and IL-1β in a concentration-dependent manner.

Experimental Example 7 Toxicity Test

The male Balb / c mice were suspended in 0.5% methylcellulose solution in the emodine prepared in Example and administered once orally at a dose of 0.5 g / kg, 1 g / kg and 2 g / kg, and the survival rate and body weight of the mouse for 7 days. Was investigated.

After the administration, the mortality, clinical symptoms, and weight changes of the animals were observed. Hematological and hematological examinations were performed. Necropsy was performed to visually observe the abdominal and thoracic organ abnormalities.

As a result, no significant clinical symptoms or dead animals were noted in all animals, and no toxic changes were observed in weight changes, blood tests, blood biochemistry tests, and autopsy findings.

As a result, the emodine of the present invention does not show a change in toxicity in rats up to 2 g / kg, therefore, the oral administration intermediate dose (LD50) was determined to be a safe substance of more than 2 g / kg.

Hereinafter, an example of the preparation of a pharmaceutical composition comprising an emodine according to the present invention will be described, but the present invention is not intended to be limited thereto but only to be described in detail.

Preparation Example 1 Preparation of Powder

A powder was prepared by mixing 20 mg of emodine, 100 mg of lactose and 10 mg of talc and filling into an airtight bag.

&Lt; Formulation Example 2 > Preparation of tablet

Tablets were prepared by mixing 20 mg of emodine, 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate, followed by compression according to a conventional method for preparing tablets.

Preparation Example 3 Preparation of Capsule

Emodine 10 mg, corn starch 100 mg, lactose 100 mg and magnesium stearate 2mg were mixed and the above ingredients were mixed according to a conventional capsule preparation method and filled into gelatin capsules to prepare a capsule.

Preparation Example 4 Preparation of Injection

10 mg of emodine, a sterile distilled water dose for injection, and a pH adjusting agent dose were mixed, and then prepared in the above-described ingredient content per ampoule (2 mL) according to a conventional preparation method for injections.

Preparation Example 5 Preparation of Health Food

Emodine 200 mg, vitamin mixture proper amount (70 μg of vitamin A acetate, 1.0 mg of vitamin E, vitamin B 1 0.13 mg, vitamin B 2 0.15 mg, vitamin B 6 0.5 mg, vitamin B 12 0.2 μg, vitamin C 10 mg, biotin 10 μg, nicotinic acid amide 1.7 mg, folic acid 50 μg, pantothenate 0.5 mg) and mineral mixture (1.75 mg ferrous sulfate, 0.82 mg zinc oxide, 25.3 mg magnesium carbonate, 15 mg potassium monophosphate, calcium diphosphate dibasic) 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, magnesium chloride 24.8 mg) were mixed, granules were prepared, and health food was prepared according to a conventional method.

Preparation Example 6 Preparation of Health Beverage

200 mg of emodine, 1000 mg of citric acid, 100 g of oligosaccharide, 2 g of plum concentrate, 1 g of taurine, and purified water were added to make it total 900 ml.The above ingredients were mixed according to a conventional method for preparing a healthy beverage, and then about 1 After stirring and heating at 85 ° C. for an hour, the resulting solution was collected by filtration into a sterilized 2 L container, sealed sterilized and then refrigerated.

Claims (7)

A pharmaceutical composition for preventing and treating allergic diseases containing an anthraquinone derivative represented by Formula 1 as an active ingredient:
[Formula 1]

In Formula 1, R ¹ and R ² are each selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, C1 to C4 alcohol or hydroxy, and R ³ is a monosaccharide. The method according to claim 1, wherein the anthraquinone derivative, R ¹ and R ² are each hydrogen, and at least one selected from methyl, methoxy, methanol, hydroxy, R ³ is a glucose allergic disease preventive and therapeutic pharmaceutical composition. The method of claim 1, wherein the anthraquinone derivative is any one selected from emodin, citreosein, emodin-8-O-β-D-glucoside, fish cion or chrysopanol for the prevention and treatment of allergic diseases Composition. The pharmaceutical composition of claim 1, wherein the anthraquinone derivative inhibits inflammatory cytokine production in mast cells and inhibits degranulation reactions from mast cells. The method according to any one of claims 1 to 4, wherein the allergic disease is any one selected from the group consisting of asthma, hypersensitivity, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, contact dermatitis and urticaria. Pharmaceutical composition for preventing and treating allergic diseases. Health food for improving allergic diseases containing an anthraquinone derivative represented by the following formula 1 as an active ingredient:
[Formula 1]

In Formula 1, R ¹ and R ² are each selected from hydrogen, C1 to C4 alkyl, C1 to C4 alkoxy, C1 to C4 alcohol or hydroxy, and R ³ is a monosaccharide. The method of claim 8, wherein the health food is a powder, granules, tablets, capsules, syrups or beverages for improving allergic diseases health foods.

Images