KR20210157899A - A composition for preventing, improving or treating allergic disease comprising 6’-hydroxy justicidin-b - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating allergic diseases, or a food composition for alleviating allergic diseases, comprising 6'-hydroxy Justicidin-B as an active ingredient. 6'-hydroxy Justicidin-B of the present invention has exhibited an excellent Th2 cytokine inhibitory effect, and exhibited an excellent anti-allergic asthmatic effect. Also, it is confirmed that 6'-hydroxy Justicidin-B has an excellent anaphylaxis inhibitory effect. Accordingly, it is possible to effectively prevent, treat, or alleviate allergic diseases by using 6'-hydroxy Justicidin-B as the active ingredient.

Description

A composition for the prevention, improvement or treatment of allergic diseases comprising 6'-hydroxy justicidin-B {A COMPOSITION FOR PREVENTING, IMPROVING OR TREATING ALLERGIC DISEASE COMPRISING 6'-HYDROXY JUSTICIDIN- B}

The present invention relates to a composition comprising 6'-hydroxy justicidin-B as an active ingredient.

More specifically, the present invention relates to a pharmaceutical composition for preventing or treating allergic diseases comprising 6'-hydroxy justicidin-B as an active ingredient.

More specifically, the present invention relates to a food composition for preventing or improving allergic diseases containing 6'-hydroxy justicidin-B.

More specifically, the present invention relates to a cosmetic composition for preventing or improving allergic diseases comprising 6'-hydroxy justicidin-B as an active ingredient.

There are many lignan compounds in Justicia procumbens , and these compounds are known to have pharmacological effects such as cytotoxicity and proliferation inhibitory action of cancer cells, antiviral action, etc. (Justicidin B: A promising Bioactive Lignan, Shiva Hemmati and Hassan Seradj, Molecules, 2016;21(7):820).

6'-hydroxyjusticidin-B is also one of the lignan-based compounds present in Rathornwort. Although there is a difference in efficacy and superiority with other lignan-based drugs depending on the type of cancer cell line, the cytotoxic effect in various cancer cells, etc. is known (Cytotoxic activity of lignans from Justicia procumbens, Hong Jin et al, Fitoterapia, 2014;94:70-6).

Allergy is defined as a phenomenon in which a living body in contact with a foreign substance called an allergen exhibits a different reaction from the normal to the substance. Allergies can be caused not only by various allergens such as pollen, drugs, vegetable fibers, bacteria, food, hair dye, and chemicals, but also by humidity, temperature, and exercise. , allergic otitis media, allergic enteritis, anaphylaxis and urticaria.

Unlike other inflammatory responses, allergic inflammatory responses are mainly caused by Th2 lymphocytes, which are activated by Th2 lymphocytes and contain several bioactive substances (cytokines) such as interleukin-4 (IL-4) or interleukin-5 (IL-5). and these physiologically active substances stimulate B lymphocytes to promote IgE antibody secretion (Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene, Shimoda K et al, Nature 1996;380 ( 6575):630-3). The secreted IgE antibody binds to FceR1 on the surface of cells such as mast cells and basophils and activates these cells. Activated cells promote the secretion of histamine, leukotriene, and prostaglandin D2 as well as various physiologically active substances through degranulation, resulting in vasodilation, smooth muscle contraction, and various allergic reactions such as mucous secretion. It is known to elicit reactions associated with sexual and respiratory diseases such as airway inflammation, airway constriction, etc. (Leukotrienes and histamine mediate IgE-dependent contractions of human bronchi: pharmacological evidence obtained with tissues from asthmatic and no-asthmatic subjects, Bjφrck T and Dahlen SE, Pulm Pharmacol 1993;6(1):87-96), (IgE, Mast Cells, Basophils, and Eosinophils, Stone KD et al, Journal of Allergy and Clinical Immunology, 125(2), S73-S80, 2010 ).

However, current oral therapeutic agents that simultaneously relieve various symptoms of allergic diseases are very limited, so the development of oral drugs with improved efficacy and safety is required. One active compound would be a suitable material for the treatment of allergic diseases.

One object of the present invention is to provide a pharmaceutical composition for preventing or treating allergic diseases comprising 6'-hydroxy justicidin-B as an active ingredient.

One object of the present invention is to provide a food composition for preventing or improving allergic diseases, comprising 6'-hydroxy justicidin-B as an active ingredient.

One object of the present invention is to provide a cosmetic composition for preventing or improving allergic diseases, comprising 6'-hydroxy justicidin-B as an active ingredient.

One object of the present invention is to provide a method for preventing, improving or treating an allergic disease, comprising administering to a subject in need thereof 6'-hydroxy justicidin-B or a composition comprising the same as an active ingredient will be.

One object of the present invention is to provide a use of 6'-hydroxy justicidin-B or a composition comprising the same for the prevention, improvement, or treatment of allergic diseases.

One object of the present invention is to provide a use of 6'-hydroxy justicidin-B or a composition comprising the same for the preparation of a medicament for the prevention, improvement, or treatment of allergic diseases.

The present invention provides a pharmaceutical composition for preventing or treating allergic diseases, comprising 6'-hydroxy justicidin-B as an active ingredient.

In one embodiment, the allergic disease may be any one or more selected from the group consisting of allergic rhinitis, allergic asthma, allergic conjunctivitis, atopic dermatitis, allergic enteritis, allergic otitis media, anaphylaxis, and urticaria.

In one embodiment, the pharmaceutical composition may contain 0.1 mg/g to 200 mg/g of 6'-hydroxy justicidin-B.

In one embodiment, the pharmaceutical composition may include only 6'-hydroxy justicidin-B as an active ingredient.

6'-hydroxy justicidin-B shows excellent bioavailability in the human body when administered orally. Accordingly, the pharmaceutical composition of an embodiment comprising 6'-hydroxy justicidin-B may exhibit excellent bioavailability.

The present invention provides a food composition for preventing or improving allergic diseases, comprising 6'-hydroxy justicidin-B as an active ingredient.

The food composition may be a health functional food. The food composition may be a beverage.

The present invention provides a cosmetic composition for preventing or improving allergic diseases, comprising 6'-hydroxy justicidin-B as an active ingredient.

The present invention provides a method for preventing, ameliorating or treating an allergic disease, comprising administering to a subject in need thereof 6'-hydroxy justicidin-B or a composition comprising the same as an active ingredient.

The composition may be a pharmaceutical composition, a food composition and/or a cosmetic composition of the present invention.

The present invention provides a method for preventing or treating an allergic disease, comprising administering 6'-hydroxy justicidin-B or a pharmaceutical composition comprising the same as an active ingredient to a subject in need thereof.

The present invention provides a method for preventing or improving an allergic disease, comprising administering to a subject in need thereof 6'-hydroxy justicidin-B or a food composition comprising the same as an active ingredient.

The present invention provides a method for preventing or improving an allergic disease, comprising applying 6'-hydroxy justicidin-B or a cosmetic composition comprising the same as an active ingredient to a subject in need thereof.

The present invention provides the use of 6'-hydroxy justicidin-B or a composition comprising the same for the prevention, improvement, or treatment of allergic diseases.

The composition may be a pharmaceutical composition, a food composition and/or a cosmetic composition of the present invention.

The present invention provides the use of 6'-hydroxy justicidin-B or a pharmaceutical composition comprising the same for the prevention or treatment of allergic diseases.

The present invention provides the use of 6'-hydroxy justicidin-B or a food composition or cosmetic composition comprising the same for the prevention or improvement of allergic diseases.

The present invention provides the use of 6'-hydroxy justicidin-B or a composition comprising the same for the preparation of a medicament for the prevention, improvement, or treatment of allergic diseases.

The composition may be a pharmaceutical composition, a food composition and/or a cosmetic composition of the present invention.

The present invention provides the use of 6'-hydroxy justicidin-B or a pharmaceutical composition comprising the same for the preparation of a medicament for the prevention, improvement or treatment of allergic diseases.

The present invention provides a use of 6'-hydroxy justicidin-B or a food composition or cosmetic composition comprising the same for the preparation of a medicament for the prevention or improvement of allergic diseases.

In one embodiment, 6'-hydroxy justicidin-B may be synthesized through organic synthesis.

6'-hydroxy justicidin-B of the present invention can inhibit the secretion of Th2 inflammatory cytokines, and exhibits an allergic asthma inhibitory effect and an anaphylactic inhibitory effect, and thus effectively prevents, treats or improves allergic diseases can do.

In the present invention, the allergic disease may include, without limitation, various diseases caused by various triggers. For example, the allergic disease may be one or more selected from the group consisting of allergic rhinitis, allergic asthma, allergic conjunctivitis, atopic dermatitis, allergic enteritis, allergic otitis media, anaphylaxis, and urticaria. In embodiments of the present invention, the allergic disease may be an allergic respiratory disease.

As used herein, the term "subject" refers to an animal, typically a mammal capable of exhibiting a beneficial effect by treatment with the composition of the present invention. By mammal is meant mammals, including humans, and the term “administering” means providing a given substance to a subject by any suitable method. It is apparent to those skilled in the art that the therapeutically effective dosage and frequency of administration for the active ingredient of the present invention will vary depending on the desired effect.

In the present invention, the term "mammal including humans" refers to mammals such as monkeys, cattle, horses, dogs, cats, rabbits, rats, and mice, and in particular includes humans. Also, such subjects include all subjects having or at risk of having symptoms of allergic disease.

As used herein, the term “prevention” means delaying the onset of a disease, disorder or condition. Prevention may be considered complete if the onset of the disease, disorder or condition is delayed for a predetermined period.

As used herein, the term "amelioration" means partially or completely alleviating, alleviating, inhibiting or delaying the onset of a disease, disorder or condition, reducing the severity, or reducing the occurrence of one or more symptoms or features. .

As used herein, the term “treatment” refers to partially or completely alleviating, ameliorating, alleviating, inhibiting or delaying the onset of a particular disease, disorder and/or condition, reducing the severity, or preventing the occurrence of one or more symptoms or features. means to reduce

The pharmaceutical composition of the present invention is in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, aerosols, injection solutions, etc. according to conventional methods for preventing and treating allergic diseases. It can be formulated and used. For example, carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

The composition of the present invention may be administered orally or parenterally (eg, application or intravenous, subcutaneous, intraperitoneal injection).

As used herein, the term "oral administration" is a method of injecting a drug by mouth for alleviating pathological symptoms, and in this specification, the term "parenteral administration" refers to subcutaneous, intramuscular, It refers to a method of intraperitoneal administration using an intravenous or tube.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the complex composition, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be prepared by mixing. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. can be used

Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. As the non-aqueous solvent and suspending agent, vegetable oils such as propylene glycol, polyethylene glycol, and olive oil, and injectable esters such as ethyl oleate may be used.

In addition, the pharmaceutical composition of the present invention may further include a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydroxy Minerals such as propyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxy benzoate, ethyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, silicon dioxide, etc. may be used. .

The pharmaceutically acceptable additive according to the present invention may be included in an amount of 0.1 to 99.9 parts by weight based on the composition, specifically, 0.1 to 50 parts by weight, but the embodiment is not limited thereto.

The dosage of the pharmaceutical composition according to the present invention should be a pharmaceutically effective amount. "Pharmaceutically effective amount" means an amount sufficient to prevent or treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level includes the formulation method, the patient's condition and weight, the patient's sex, and age. , can be variously selected by those skilled in the art according to factors such as the degree of disease, drug form, administration route and duration, excretion rate, reaction sensitivity, and the like. An effective amount will vary depending on the route of treatment, the use of excipients, and the potential for use with other agents, as will be appreciated by those skilled in the art.

An amount effective to prevent or treat an allergic disease is administered in single or multiple doses, alone or in combination with one or more other compositions (such as other therapeutic agents for allergic diseases), which provides the desired performance or objective or subjective benefit in the subject. It can mean quantity.

The dosage or dosage of the pharmaceutical composition according to the present invention varies depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease, but is 0.001 on an adult basis mg/kg to 1000 mg/kg may be administered in one to several divided doses.

In another aspect of the present invention, there is provided a cosmetic composition for preventing or improving allergic diseases comprising 6'-hydroxy justicidin-B as an active ingredient.

In the present invention, the cosmetic composition is a softening lotion, astringent lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, It may be a formulation selected from the group consisting of body oil, body essence, makeup base, foundation, hair dye, shampoo, conditioner and body cleanser.

The cosmetic composition of the present invention can be prepared in various forms according to a conventional cosmetic preparation method using the 6'-hydroxy justicidin-B, and a stabilizer, solubilizer, It may contain conventional adjuvants such as vitamins, pigments, and flavorings.

In addition, when the cosmetic composition is prepared in the form of cosmetic products containing the 6'-hydroxy justicidin-B, shampoo, hair lotion, hair cream, hair gel, etc. It can be used after dilution.

The cosmetic composition of the present invention is particularly preferably prepared in the form of a lotion, lotion, cream, or essence.

In the cosmetic composition of the present invention, 6'-hydroxy justicidin-B may be added to the cosmetic in an amount of 0.1% to 10% by weight based on the total liquid weight, and 0.001 to about the total dry weight of the cosmetic composition. It may be added to the cosmetic in an amount of 5% by weight, preferably 0.01 to 3% by weight.

Numerical values described in the present specification above should be interpreted as including equivalent ranges unless otherwise specified.

Items mentioned in each of the uses, compositions, and prevention, improvement and/or treatment methods of the present invention may be applied as long as they do not contradict each other.

The 6'-hydroxy justicidin-B of the present invention excellently inhibited the differentiation of Th2 cells related to allergic diseases, and was effective in inhibiting asthma diseases even when administered at low concentrations in the Balb/c mouse model of allergic asthma. shows an excellent effect. Accordingly, the pharmaceutical composition, food composition, and cosmetic composition comprising 6'-hydroxy justicidin-B according to the present invention can be widely used as an agent for preventing, treating or improving allergic diseases.

1 is a diagram showing the chemical structure of 6'-hydroxy justicidin-B according to the present invention.

Hereinafter, preferred preparation examples, examples and preparation examples are presented to help the understanding of the present invention. However, the following Preparation Examples, Examples and Formulation Examples are only provided for easier understanding of the present invention, and the content of the present invention is not limited by the Preparation Examples, Examples and Formulation Examples.

Preparation Example 1: Preparation of 6'-hydroxy justicidin-B through organic synthesis

6'-hydroxy justicidin-B was synthesized through the following process. The structure of 6'-hydroxy justicidin-B is as shown in FIG. 1 .

Step 1: 6,7-dimethoxy-3-oxo-1,3-dihydronaphtho [2,3-c] furan-4-yl trifluoromethanesulfonate (3.0 g, 7.65 mmol) was mixed with dioxane (90ml) After dissolving in a solvent, 5-methoxymethoxy-6-(4,4,5,5,-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1 ,3]dioxole (2.83g, 9.18mmol), [1,1'-bis(diphenyl phosphino)ferrocene]dichloropalladium(II) (1.12g, 1.53mmol) and lithium hydroxide monohydrate (642mg, 15.3mmol) ) were sequentially added under a nitrogen atmosphere. After raising the temperature to 60 °C, the reaction was carried out for 4 hours. After cooling to room temperature, water was added to terminate the reaction, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel column chromatography, and the title compound 6,7-dimethoxy-9-(6-methoxymethoxy-benzo[1,3]dioxol-5-yl)-3H-naphtho[2,3] -c] furan-1-one (9 g, 21.2 mmol) was obtained.

¹ H NMR: (DMSO- d ₆ , 400 MHz) δ 7.92 (s, 1H), 7.48 (s, 1H), 6.95 (s, 1H), 6.87 (s, 1H), 6.73 (s, 1H), 6.08 (d, 2H, J = 2.8 Hz), 5.38 - 5.49 (m, 2H), 4.90 (d, 1H, J = 6.8 Hz), 4.81 (d, 1H, J = 6.8 Hz), 3.93 (s, 3H) , 3.65 (s, 3H), 2.93 (s, 3H).

Step 2: 6,7-dimethoxy-9-(6-methoxymethoxy-benzo[1,3]dioxol-5-yl)-3H-naphtho[2,3-c]furan-1-one (8g, 18.9mmol) was dissolved in ethanol (80ml), and 44ml of 12M HCl was added dropwise, followed by reaction at 50°C for 12 hours. After the reaction was completed, 100 ml of water was added, and the mixture was extracted with dichloromethane (200 ml, 100 ml, 50 ml). The obtained organic layer was washed with water (150ml) and brine (100ml), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel column chromatography, and the title compound 9-(6-hydroxy-benzo[1,3]dioxol-5-yl)-6,7-dimethoxy-3H-naphtho[2,3-c] ] furan-1-one (6'-HJB, 5.20 g, 13.7 mmol, 72.5%) was obtained.

¹ H NMR: (DMSO- d ₆ , 400 MHz) δ 9.01 (s, 1H), 7.88 (s, 1H), 7.46 (s, 1H), 6.95 (s, 1H), 6.63 (s, 1H), 6.57 (s, 1H), 6.00 (d, 2H, J = 2.00 Hz), 5.41 (s, 2H), 3.93 (s, 3H), 3.66 (s, 3H). The purity of 6'-hydroxy justicidin-B was 98.76%.

Example 1. Comparative experiment on the effect of inhibiting differentiation from CD4 T cells to Th2 cells

In order to confirm the inhibitory effect of 6'-hydroxy justicidin-B on differentiation into Th2 cells, an experiment was conducted as follows. Splenocytes were isolated using spleen isolated from Balb/c mice, and CD4 T cells were isolated from splenocytes using a CD4 T cell isolation kit (Miltenyi Biotec). did ^{The isolated CD4 T cells were 1X10 6} in RPMI medium containing 5% fetal bovine serum (FBS), antibiotics (penicillin 100 U/mL, streptomycin 100 μg/mL), and 50 μM 2-mercaptoethanol. After dilution to a cell/mL concentration, 500 μl/well was dispensed into a 48-well plate coated with anti-CD3/anti-CD28 antibody, and incubated for 48 hours at _{37° C. 5% CO 2 in an incubator.} At this time, in order to induce and maintain CD4 T cells into Th0 cells, 20 ng/mL of interleukin-2 (IL-2) was additionally treated, and to induce Th0 cells into Th2 cells, 20 ng/mL of interleukin-2 ( IL-2), 100 ng/mL of interleukin-4 (IL-4), 10 μg/mL of interferon-gamma antibody (anti-IFNγ antibody), 10 μg/mL of interleukin-12 antibody (anti-IL12 antibody) was added, and at this time, 6'-hydroxy justicidin-B prepared in Preparation Example 1 was treated. The medium of the 24-well plate was used to measure the secretion level of interleukin-5 (IL-5), a Th2 inflammatory cytokine. First, in order to measure cytokines secreted by Th2, the medium in a 24-well plate was collected, and only the supernatant was separated by centrifugation at 800xg for 5 minutes. (ELISA, Goma Biotech) The degree of secretion of these cytokines was measured using an experiment. The degree of inhibition of IL-5 secretion by the drug was calculated using the following [Equation 1].

[Equation 1]

test group Concentration (nM) IL-5 inhibitory ability (%) 6'-hydroxy
Justicidin-B 0.1 44.9±0.90 0.5 44.9±2.71 One 50.1±1.09 10 57.2±1.29

Referring to Table 1 above, the excellent inhibitory effect on interleukin-5 secretion of 6'-hydroxy justicidin-B is confirmed. In particular, it is confirmed that 6'-hydroxy justicidin-B achieves an excellent IL-5 secretion inhibitory effect even at a low concentration. From this, the excellent inhibitory effect of 6'-hydroxy justicidin-B into Th2 cells and the excellent prevention, improvement, or therapeutic effect of 6'-hydroxy justicidin-B on allergic diseases were confirmed. .

Example 2. Efficacy evaluation in OVA asthma Balb/c mouse model

After purchase, 6-week-old Balb/c mice were acclimatized for 1 week, and 0.1% egg white albumin (OVA 1 mg/mL, Al(OH) ₃ 20 mg/mL) was prepared on days 0 and 14 from one week after acclimatization, in an amount of 100 μl/mouse. systemic sensitization by intraperitoneal injection. After the final systemic sensitization, the test drugs were orally administered for 10 days every day from one week after the final systemic sensitization, and an hour later, 0.2% egg white albumin solution was sprayed using a nebulizer (PARI Boy SX, Germany GmbH) and inhaled for 1 hour. . After the final sensitization (day 30), an autopsy was performed 5 hours later to obtain blood and lung lavage, and the lung tissue was fixed in 10% neutral formalin. After that, blood and lung lavage were used for IgE and Th2 cytokines and immune cytometry, and the lung tissue was cut and prepared into slides, and the tissue was observed by performing H&E staining. Observation of lung tissue was photographed at 400 times the microscope, and the thickness of the lung epithelium of the photographed tissue was measured using the Image-pro Plus 6.0 program. The results are shown in Tables 2 and 3, and the inhibitory ability was calculated using [Equation 1] described above in Example 1.

Test group (n=5) drug
density
(mg/kg) serum
(Inhibition %, Mean±SE) Lung lavage fluid (inhibitory %, Mean±SE) IgE IgE IL-5 eosinophils total number of cells 6'-hydroxy justicidin-B 0.1 66.9±12.5 70.8±7.5 68.2±6.3 84.2±5.1 87.8±7.2 Montelukast (positive control) 10 -5.6±20.1 60.2±4.2 37.0±16.7 43.7±13.9 12.7±15.2

Test group (n=5) Drug Concentration (mg/kg) Lung epithelial thickness (% inhibition, Mean±SE) 6'-hydroxy justicidin-B 0.1 44.2±6.4 monterukast
(positive control group) 10 -25.6±55.7

As shown in Table 2, when 0.1 mg/kg of 6'-hydroxy justicidin-B was administered, various indicators related to allergic asthma disease were 100 times higher than the concentration of 6'-hydroxy justicidin-B. It was confirmed that the montelukast at a high dose of 10 mg/kg was significantly reduced, and as shown in Table 3, the lung epithelial thickness was also significantly reduced.

Through this, the excellent preventive, ameliorating or therapeutic effect of 6'-hydroxy justicitin-B for allergic asthma is confirmed.

Example 3. Efficacy evaluation in anaphylaxis ICR mouse model

6-week-old ICR mice were grouped based on body weight, and anaphylaxis was induced by intraperitoneal administration of Compound 48/80 (Sigma #C2313) at a concentration of 16 mg/kg. The 6'-hydroxy justicidin-B and the positive control group DSCG (Cromolyn sodium, Sigma #C0399) 250 mg/kg were administered intraperitoneally 1 hour before anaphylaxis induction, respectively, and mortality (mortality) for 30 minutes after anaphylaxis induction. ) was observed, and the results are shown in Table 4. Anaphylaxis inhibitory ability was calculated using the following [Equation 2].

[Equation 2]

Test group (n=10) Drug Concentration (mg/kg) Anaphylaxis inhibitory ability (%) 6'-hydroxy
Justicidin-B 0.1 43 DSCG (positive control) 200 14

As shown in Table 4, in an animal experiment on anaphylaxis, a systemic allergic disease, 6'-hydroxy justicidine at a concentration of 1/2000 of DSCG compared to the decrease in anaphylaxis mortality when DSCG was administered. -B administration had a greater reduction in mortality. Through this, the excellent prevention, improvement or therapeutic effect of 6'-hydroxy justicidin-B for allergic diseases is confirmed.

Formulation Example 1: Preparation of pharmaceuticals

1-1. Preparation of powders

6'-hydroxy justicidin-B 100mg

Lactose 100mg

talc 10mg

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

1-2. manufacture of tablets

6'-hydroxy justicidin-B 100mg

Corn Starch 100mg

Lactose 100mg

2mg magnesium stearate

After mixing the above ingredients, tablets are prepared by tableting according to a conventional manufacturing method of tablets.

1-3. manufacture of capsules

6'-hydroxy justicidin-B 100mg

Corn Starch 100mg

Lactose 100mg

2mg magnesium stearate

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

1-4. manufacture of injections

6'-hydroxy justicidin-B 100mg

Appropriate amount of sterile distilled water for injection

Appropriate amount of pH adjuster

According to a conventional method for preparing injections, the content of the above ingredients per 1 ampoule (2 ml) is prepared.

1-5. Preparation of liquids

6'-hydroxy justicidin-B 100mg

20 g sugar

Isomerized sugar 20g

Lemon flavored amount

Add purified water to make the total volume of 1,000 ml. After mixing the above ingredients according to a conventional liquid preparation method, it is filled in a brown bottle and sterilized to prepare a liquid preparation.

1-6. manufacture of inhalants

6'-hydroxy justicidin-B 100mg

15 g of 1,1,1,2-tetrafluoroethane

1.5 g of absolute ethanol

Citric acid (anhydrous) 0.05 mg

Polyethylene glycol 500mg

According to a conventional method for preparing inhalants, the above ingredients are mixed and filled in a container.

Formulation Example 2: Preparation of food

6'-hydroxy justicidin-B 100mg

appropriate amount of vitamin mixture

70 μg 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

Biotin 10 μg

Nicotinamide 1.7 mg

50 μg of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture appropriate amount

Ferrous sulfate 1.75 mg

Zinc oxide 0.82 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

The composition ratio of the above vitamin and mineral mixture is mixed composition with ingredients suitable for health functional food as a preferred embodiment, but the mixing ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food manufacturing method. Next, according to a conventional method, it can be used for manufacturing a health functional food composition (eg, nutritional candy, etc.).

Formulation Example 3: Preparation of beverage

6'-hydroxy justicidin-B 100mg

citric acid 1000 mg

100 g of oligosaccharides

2 g of plum concentrate

1 g taurine

Total 900 ml by adding purified water

After mixing the above ingredients according to the usual health functional beverage manufacturing method, after stirring and heating at 85°C for about 1 hour, the resulting solution is filtered and acquired in a sterilized 2L container, sealed and sterilized, then refrigerated. It is used to prepare the health functional beverage composition of the present invention. Although the composition ratio is prepared by mixing ingredients suitable for relatively favorite beverages in a preferred embodiment, the blending ratio may be arbitrarily modified according to regional and national preferences such as demand class, demanding country, and use purpose.

Formulation Example 4: Preparation of cosmetics

6'-hydroxy justicidin-B 100mg

Glycerin 3.0 mg

Hydrogenated Lecithin 1.0 mg

cetostearyl alcohol 2.0 mg

Polysorbate 60 1.5 mg

Antioxidant 0.3 mg

Appropriate amount of preservative

Purified water appropriate amount

According to a conventional cosmetic preparation method, the above ingredients were mixed to prepare a cosmetic.

Claims (7)

A pharmaceutical composition for preventing or treating allergic diseases comprising 6'-hydroxy justicidin-B as an active ingredient.
According to claim 1,
The allergic disease is a pharmaceutical for preventing or treating any one or more allergic diseases selected from the group consisting of allergic rhinitis, allergic asthma, allergic conjunctivitis, atopic dermatitis, allergic enteritis, allergic otitis media, anaphylaxis and urticaria. composition.
According to claim 1,
The allergic disease is an allergic respiratory disease, a pharmaceutical composition for preventing or treating an allergic disease.
According to claim 1,
The pharmaceutical composition is a pharmaceutical composition for the prevention or treatment of allergic diseases comprising 6'-hydroxy justicidin-B 0.1 mg/g to 200 mg/g.
A food composition for preventing or improving allergic diseases comprising 6'-hydroxy justicidin-B as an active ingredient.
6. The method of claim 5,
The food is a health functional food, a food composition for the prevention or improvement of allergic diseases.
A cosmetic composition for preventing or improving allergic diseases comprising 6'-hydroxy justicidin-B as an active ingredient.

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