KR20090084159A - Composition for the treatment of immune-related diseases containing persimmon extract or tannin as an active ingredient - Google Patents

Abstract

A composition for treating immune related diseases is provided to suppress the expression of MMP-2 or MMP-9 and treat inflammation by oxidative stress. A composition for treating immune related diseases comprises Diospyros kaki Thunb. Extract or tannin as an active ingredient. The immune related diseases are selected among atopic dermatitis, asthma or rhinitis. The Diospyros kaki Thunb. Extract or tannin has the effect of suppressing the expression of MMP-2 or MMP-9. A method for manufacturing Diospyros kaki Thunb. Extract containing the tannin as an active ingredient comprises: a step of smashing the Diospyros kaki Thunb.; a step of extracting with low alcohol of C3-6, water, low organic acid of C3-6, low alcohol ester of C3-6, low ketone of C3-6 and halogenated hydrocarbon of C3-6; and a step of collecting extract.

Description

Composition for Treating Immune-Related Diseases Containing Persimmon Extract or Tannin as an Active Ingredient {Composition for Treating Immune Related Disease Comprising Extract of Diospyros kaki Thunb. or Tannin as an Active Ingredient}

The present invention persimmon containing tannin as an active ingredient ( Diospyros kaki Thunb.) Relates to extracts or tannin (tannin) in immune related disease pharmaceutical composition containing as an active ingredient, more specifically, a sense (the broken Diospyros kaki Thunb.), And then, a lower alcohol of C _{3 -6} Immune containing diospyros kaki Thunb. Extract or tannin as an active ingredient containing tannin extracted with a solvent selected from the group consisting of water, lower organic acids, lower alcohol esters, lower ketones and halogenated hydrocarbons The present invention relates to a pharmaceutical composition for treating related diseases and a health food.

Atopic dermatitis is a representative disease among immune related diseases, and it has been known as an important allergic disease along with asthma, rhinitis, rash and the like.

Atopic dermatitis is a chronic and chronic skin disease with severe itching and inflammation.It develops as time goes by after the onset, and it becomes irresistible. This occurs because of the itching caused by this vicious cycle of scratching the skin again.

Atopy is commonly referred to as an allergy, which means hypersensitivity. When an alien substance or allergen enters a human body, an antibody reacts with the antigen and tries to convert it into a harmless substance. This response is called an immune response. However, in some people, the reaction is so strong that it appears to be harmful to the body, a form of which is known as atopic dermatitis (atopic dermatitis).

Atopy is closely related to T-cell, and T-cell is differentiated into Th1 T-cell and Th2 T-cell by cytokine. In this case, Th1 T-cell is typically represented by interferon-γ ( interferon-γ) and interleukin-12 (IL-12), and in the case of Th2 T-cell, interleukin-4 (IL-4), 5, 9, 12, 13, etc. Known. Of these two T-cells, Th1 T-cells are known to support the cellular immune response of macrophages, and Th2 T-cells are known to have a function to assist the humoral immune response of B-cells (Gemmell and seymour, Crit. Rev. Oral Biol . Med., 5 (3-4) : 249, 1994).

In addition, it has been reported that atopy has a deep relationship with humoral immune response as a type I immune response and also has a strong relationship with Th2 T-cell activity (Larch et. al ., J. Allergy Clin. Immunol . , 111 (3) : 450, 2003).

In recent years, the onset of atopy is rapidly increasing irrespective of age and gender, and it is known that this is due to water pollution and imbalance of the human immune system due to industrialization.

Diospyros kaki Thunb.) Is a unique fruit tree of East Asia, native to Korea, China, and Japan. The main component of the persimmon sugar is 15 to 16%, the content of glucose and fructose is high, and there is a slight difference between sweet persimmon and red persimmon. The astringent taste is tannin, called diosphrine, which is easily soluble because it is water soluble. The astringent taste disappears when acetaldehyde binds to tannin and becomes insoluble. The dark spots on the persimmons and rinds of sweet persimmons are tannin-insoluble tannin cells. As a component, it is rich in vitamins A and B, vitamin C contains 30-50 mg in 100 g, and also contains pectin and carotenoids. The color of the skin is due to the carotenoid pigment, and the content of lycopen, which is a dark orange, is related to the autumn sunshine conditions.

Tannin is an off-white-light brown amorphous powder, shiny scaly or spongy substance with a odorless or slightly peculiar odor and astringent taste. It is composed of gallotannis obtained by solvent extraction of gall or molar product. It is soluble in water, acetone, ethanol, etc., and insoluble in benzene, chloroform and ether. In particular, tannins dissolve in 1 ml of warm glycerin. Tannins are not chemically acids, but are commonly referred to as tannic acid by the commercial name, and are commercially distinguished from concentrated tannins and other tannins.

Diospyros kaki In the prior art related to Thunb.), The use of gallic acid derivatives, the main constituents of tannins, among the yulpi, pine needles, hops, persimmon extracts and persimmon extracts (Korean Patent Publication No. 10-2000-0056054) and persimmon extracts Method of preparing soap using Korean Patent Application Publication No. 10-2004-0017981, and persimmon leaf extract and its glycoside, astragalin, inhibited atopic progression and synergism of IEG serum in atopic dermatitis mouse model. (Kotani et al ., J. Allergy Clin . Immunol . , 106 (1) : 159, 2000), Results of oral administration of persimmon leaf extract in atopic dermatitis-induced mouse models to improve skin symptoms and transdermal moisture loss (Matsumoto et. al ., Br . J. Dermatol ., 146 (2) : 221, 2002).

However, persimmon containing tannin as an active ingredient in the above-mentioned research reports ( Diospyros kaki The therapeutic effect of Thunb.) Extract or tannin on atopy, asthma or rhinitis has not been reported at all.

Thus, the present inventors have analyzed the components of various natural substances that have already been proven to overcome the side effects of using steroid-based ointments that are currently used as anti-atopic drugs, persimmon containing tannin as an active ingredient ( Diospyros kaki Thunb.) Extracts or tannins have been shown to suppress immune-associated cell growth and inhibit the expression of MMP-2 or MMP-9 in atopic dermal animal models.

The main object of the present invention is a persimmon containing tannin as an active ingredient ( Diospyros kaki To provide a pharmaceutical composition for the treatment of immune-related diseases containing Thunb.) Extract or tannin as an active ingredient.

Another object of the present invention to provide a health food for improving immune-related diseases, including persimmon ( Diospyros kaki Thunb.) Extract or tannin (tannin) and food acceptable food additives containing an active ingredient.

In order to achieve the above object, the present invention persimmon containing tannin as an active ingredient ( Diospyros kaki Provided is a pharmaceutical composition for treating immune-related diseases containing Thunb.) Extract or tannin as an active ingredient.

The present invention also relates to persimmon containing tannin as an active ingredient ( Diospyros kaki Provides a health food for improving immune-related diseases containing Thunb.) Extract or tannin as an active ingredient.

The pharmaceutical composition according to the present invention exhibits an inhibitory effect on immune-related cell growth and suppresses the expression of MMP-2 or MMP-9 in an atopy-induced animal model, and thus can be used as an effective medicine for the treatment of atopic, asthma or rhinitis.

The present invention in one aspect, persimmon containing tannin as an active ingredient ( Diospyros kaki It relates to a pharmaceutical composition for treating immune-related diseases containing Thunb.) Extract or tannin as an active ingredient.

In the present invention, the immune-related disease may be characterized in that it is selected from the group consisting of atopy, asthma or rhinitis.

In the present invention, the persimmon ( Diospyros kaki Thunb.) Extract or tannin containing the tannin as an active ingredient may have a function of inhibiting the expression of MMP-2 or MMP-9.

(. Diospyros kaki Thunb) In the present invention, the tannin, the sense of containing as an active ingredient (. Diospyros kaki Thunb) extract of (a) a sense of the cell lysate and then, a lower alcohol, water, a C _3-6, C _{3 -} extracting with a solvent selected from the group consisting of _6-lower organic acids, halogenated hydrocarbons, C _{3 -6} lower alcohol esters, C _{3 -6} lower ketones and C _{3 -6} of; And (b) recovering the extract.

The lower alcohol of C _3-6 is preferably ethanol (CH ₂ H ₅ OH) or methanol (methanol; CH ₃ OH), and the lower organic acid of C _3-6 is butyric acid or Preference is given to using caproic acid. In addition, the lower alcohol ester of a C _3-6 dimethyl ether (dimethyl ether), ethyl ether (methyl ethyl ether), and diethyl ether may be selected from the group consisting of (diethyl ether), lower ketone of C _3-6 include dimethyl ketone (dimethyl ketone), ethyl-methyl ketone (methyl ethyl ketone) and diethyl ketone may be selected from the group consisting of (diethyl ketone), a halogenated hydrocarbon group of C _{3 -6} is carbon tetrachloride (carbon tetrachloride) or Trichlorethylene (trichlorethylene) is preferred, but not limited to.

In the present invention, persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extract Diospyros kaki Thunb.) It may be characterized in that the flesh extract.

Sense of the present invention (Diospyros kaki Thunb.) Extract can be prepared by the following method. Diospyros kaki Thunb.) Was purchased / harvested and powdered and then diospyros kaki Thunb.) Extracted by hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction for 12 ~ 36 hours by adding water of about 2 ~ 10 times the weight of the sample, followed by centrifugation. Japanese persimmon ) extract can be obtained.

Tannin of the present invention can be prepared by the following method.

Persimmon obtained above ( Diospyros kaki The Thunb.) Extract may be bathed at 50 to 100 ° C. for 10 to 60 minutes and then cooled to obtain tannin.

Persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extracts or tannins were tested using hematoxylin-eosin staining and immunohistochemical staining to confirm the therapeutic effects of immune-related diseases. It was confirmed that the expression of matrix metal protease-2 (MMP-2) or matrix metal protease-9 (MMP-9) was suppressed.

MMP-2 and MMP-9 are important protein markers for cell motility, and their function in immunological diseases has recently been highlighted, and has been studied as targets for new therapeutic agents. It is known that the concentration and migration of cells by immune response depends on the motility of immune cells. In this case, knock-out of MMP-2 and MMP-9 significantly reduces the concentration of immune cells. Induction of asthma response by autoimmune diseases by inhibiting MMP expression and function in mice is known to reduce the induction of asthma response compared to normal expression of MMP (Greenlee KJ et. al ., J. Immunol., 177 (10) : 7312, 2006).

Sense of the present invention (Diospyros kaki Since Thunb.) Extract is a natural substance, it is not toxic and can be continuously used in large amounts as a medicine.

The composition comprising the persimmon extract of the present invention can be used in combination or formulated with drugs such as antihistamines, anti-inflammatory analgesics, anticancer agents and antibiotics that are already in use.

Pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, or 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, respectively, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories and sterile injectable solutions 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, 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 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 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.

The preferred dosage of the persimmon extract of the present invention depends 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 0.0001 to 10 mg / kg, preferably 0.001 to 10 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 extract of the present invention can be administered to mammals such as mice, 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 cerebrovascular injections.

In another aspect, the present invention is a persimmon containing tannin as an active ingredient ( Diospyros kaki Thunb.) Extract or tannin (healthy foods) for improving immune-related diseases, including tannins and food acceptable food additives.

In the present invention, the immune-related disease may be selected from the group consisting of atopy, asthma or rhinitis.

In the present invention, persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extract or tannin may be characterized by having a function of inhibiting the expression of MMP-2 or MMP-9.

In the present invention, persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extract is (a) Diospyros kaki Thunb.), And then the crushed, C _{3 -6} of a lower alcohol, water, halogenated hydrocarbons, C _{3 -6} lower organic acid, a lower alcohol ester of a C _{3 -6,} C _{3 -6} lower ketones and C _{3 -6} of Extracting with a solvent selected from the group consisting of: And (b) recovering the extract.

A lower alcohol of C _{3 -6} ethanol _{(ethanol; CH 2 H 5 OH} ) or methanol (methanol; CH ₃ OH) a is preferably used, and the lower organic acid is a C _{3 -6} acid (butyric acid) or Preference is given to using caproic acid. In addition, C-lower alcohol ester of _3-6 is dimethyl ether (dimethyl ether), ethyl ether (methyl ethyl ether), and diethyl ether may be selected from the group consisting of (diethyl ether), lower ketone of C _3-6 include dimethyl ketone (dimethyl ketone), ethyl-methyl ketone (methyl ethyl ketone) and diethyl ketone may be selected from the group consisting of (diethyl ketone), a halogenated hydrocarbon group of C _{3 -6} is carbon tetrachloride (carbon tetrachloride) or Trichlorethylene (trichlorethylene) is preferred, but not limited to.

In the present invention, persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extract Diospyros kaki Thunb.) It may be characterized in that the flesh extract.

The compound containing the extract of the present invention or a pharmaceutically acceptable salt thereof may be used as a main ingredient or additive and adjuvant of food in the preparation of various functional foods and health foods.

As used herein, the term "functional food" means a food product having improved functionality of a general food product by adding the persimmon extract of the present invention to a general food product. Functionality can be roughly divided into physical properties and physiological functions. When the extract of the present invention is added to general foods, the physical properties and physiological properties of general foods will be improved, and the present invention comprehensively describes foods having such improved functions as 'functional foods'. 'Is defined.

For example, by using the anti-asthma, anti-atopic or rhinitis inhibitory effect of the extract of the present invention can be prepared a functional food for improving atopic, asthma or rhinitis. In addition, it will be possible to produce a functional fortified food using atopic, asthma or rhinitis improving effect.

In addition to the above, the extract 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. In addition, the persimmon extract of the present invention may contain natural fruit juice and fruit flesh for the production of fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is generally selected in the range of 0.01 to 20 parts by weight per 100 parts by weight of the persimmon extract of the present invention.

Hereinafter, the present invention will be described in more detail with reference to 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 limited by these examples.

Example 1: Preparation of Persimmon Extract and Tannin

1-1. Preparation of Persimmon Extract

      Four persimmons are collected from 1, 2, 3, and 4th (7, 8, 9, and October), starting from June, which is the immature fruit, to October. After crushing using a mortar or pestle, 1 liter of distilled water was added to 100 g of each, followed by extraction at room temperature for 24 hours, followed by dilution of the concentrated dry powder through lyophilization.

1-2. Extraction and Content Measurement of Tannin Components from Persimmon Extracts

      The persimmon extract obtained in Example 1-1 was bathed at 80 ° C. for 30 minutes and then cooled to extract the tannin component. The amount of tannin, one of the representative polyphenols, was measured for the extracted tannins and commercially available tannins (Sigma). HPLC (high-pressure liquid chromatography) analysis conditions were as follows.

Instrument: PerkinElmer series 200

 Column: C18 (150mm × 4.6mm)

Resolving solvent: acetonitrile: DW (90: 10)

Detector: UV 280nm

Retention time: 20 minutes

As a result, as shown in Figure 1, it was confirmed that the amount of tannin is different by the time of the persimmon extract harvested, of which the highest amount of tannin in the first pulp extract collected in July, Increasingly, the tannins were reduced, resulting in more than 50% reduction of the tannins extracted in the last October compared to the first pulp extracts collected in July .

Example 2: Inhibitory Effect of Persimmon Extract on Immune Diseases

2-1 . Establish animal model to confirm atopy inhibitory activity

An atopy model using a mouse was used for self-development of an animal model for verifying the atopy inhibitory effect of the persimmon extract obtained in Example 1-1.

Balb / c mice 6-week-old males were used, and atopy was induced by applying 25 ul of 0.15% DNFB (2,4-dinitrofluorobenzene) to the back. At this time, after the start of sensitization, apply twice a week for three days, the last two times, and then give a time that can be a natural induction for about 4 days, after 4 days 25 ul persimmon extract 2 days 1 on atopy induced back 1 The final application five times for 10 days each time to verify the atopic inhibition effect. The positive control group was tested by applying 25 ul of Atoclear ointment (Dong-Sung Pharm., Korea ) to the affected area.

2-2 . Hematoxylin-eosin staining confirms atopic inhibition

After the incision of the epithelial tissue of the atopic dermatitis animal model of Example 2-1, the fat was removed and placed in 10% formalin for about 2 days, the tissue was cut to a thickness of 0.1 mm, and then slices were placed in a slide cover. The prepared tissue sections were stained using a hematoxylin-eosin staining method and observed with a fluorescence microscope.

      As a result, as shown in Figure 2, in the atopy-induced group, immune-related cells increased by five times or more as compared to the untreated group, and the increase in immune-related cells was suppressed in the first pulp extract treated group as compared to the untreated group. I could see it.

2-3 . Determination of Expression Inhibitory Activity of MMP-2 and MMP-9 by Immunohistochemical Staining

      After the incision of the epithelial tissue of the atopic dermatitis animal model of Example 2-1, the fat was removed and placed in 10% formalin for about 2 days, the tissue was cut to a thickness of 0.1 mm, and then slices were placed in a slide cover. After staining the prepared tissue sections using immunohistochemical staining, the expression of MMP-2 and MMP-9 was observed by fluorescence microscopy.

      As a result, as shown in Figure 3, in the atopy-induced group, the cells related to immunity were increased up to five times or more compared with the untreated group, but in the first pulp extract treated group, at least 50% compared to the untreated group. The expression of MMP-2 was suppressed up to 100% level.

In addition, as shown in Figure 4, in the atopy-induced group, the cells related to immunity were increased up to five times or more compared to the untreated group, but in the first pulp extract treated group at a minimum of 60% compared to the untreated group. The expression of MMP-9 was suppressed up to 90%.

2-4 . Determination of Interleukin-4 and Interleukin-13 Expression Inhibition Activity

Serum was obtained by centrifuging blood taken from the atopy-induced animal model of Example 2-1, and then interleukin-4 antibody was attached to 96 well plates, and a non-specific protein binding solution was added to each well. After adding to the standard and the sample was added to the substrate solution and the reaction stop solution was measured at 450nm.

      As a result, as shown in Figure 5, in the atopy-induced group, the absorbance value was measured to be high, and when comparing the first pulp extract treatment group and the atopy-induced group, the first pulp extract treatment group was up to two times or more interleukin- 4 It was confirmed that the expression inhibitory effect.

     In addition, as shown in Figure 6, in the atopy-induced group, the absorbance value was measured to be high, and when comparing the first pulp extract treatment group and the atopy-induced group, the primary pulp extract treatment group was up to 1.7 times or more interleukin-13 It was confirmed that the expression inhibitory effect.

Example 3: Tannins Inhibit Immune Diseases

3-1 . Establish animal model to confirm atopy inhibitory activity

An atopy model using a mouse was used for the self-development of an animal model for verifying the atopic inhibition effect of tannin obtained in Example 1-2.

A 6-week-old male Balb / c mouse was used, and atopy was induced by applying 25 ul of 0.15% DNFB (2,4-dinitrofluorobenzene) to the back. At this time, after the start of sensitization, apply twice a week for 3 days twice, give 4 hours of natural induction, and after 4 days, 25 ul of tannin is applied once a day for 2 days after atopic dermatitis. The final application 5 times for 10 days to verify the atopic inhibition effect. As a positive control, 25 μl of Atoclear ointment was applied to the affected area.

3-2 . Hematoxylin-eosin staining confirms atopic inhibition

After cutting the epithelial tissue of the atopy-induced animal model of Example 3-1, the fat was removed and placed in 10% formalin for about 2 days, the tissue was cut to a thickness of 0.1mm, and then slices were placed in a slide cover. The prepared tissue sections were stained using a hematoxylin-eosin staining method and observed with a fluorescence microscope.

       As a result, as shown in Figure 7, the atopy-induced group increased the immune-related cells more than five times compared to the untreated group, the tannin-treated group had an effect of suppressing immune cell growth similar to that of the second pulp extract treatment group. Could see.

3-3. Determination of Expression Inhibitory Activity of MMP-2 and MMP-9 by Immunohistochemical Staining

After cutting the epithelial tissue of the atopy-induced animal model of Example 3-1, the fat was removed and placed in 10% formalin for about 2 days, the tissue was cut to a thickness of 0.1mm, and then slices were placed in a slide cover. After staining the prepared tissue sections using immunohistochemical staining, the expression of MMP-2 and MMP-9 was observed by fluorescence microscopy.

      As a result, as shown in Figure 8, in the atopy-induced group, cells related to immunity were increased up to five times or more compared with the untreated group, but in the tannin-treated group, MMP level was about 85% compared to the atopy-induced group. The expression of -2 was seen to be suppressed.

In addition, as shown in Figure 9, in the atopy-induced group, cells related to immunity were increased up to five times or more compared to the untreated group, but in the tannin-treated group, the MMP- level was about 90% compared to the atopy-induced group. 9 expression was suppressed.

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.

1 is a diagram showing the results of HPLC analysis of tannins and persimmon tannins of persimmon extract.

Figure 2 shows the experimental results measured by the hematoxylin-Eosin (HE) staining method in atopic dermatitis-treated animal model treated with persimmon extract (1: untreated group, 2: atopy Triggered group, 3: Atoclear ointment treated group, 4: primary pulp extract treated group, 5: secondary pulp extract treated group, 6: tertiary pulp extract treated group and 7: fourth pulp extract treated group).

Figure 3 is a measure of the effect of persimmon extract on the expression of MMP-2 in atopic dermatitis animal model treated persimmon extract (1: no treatment group, 2: atopic dermatitis group, 3: atopic clear ointment treatment group, 4 : Primary pulp extract treatment group, 5: secondary pulp extract treatment group, 6: tertiary pulp extract treatment group and 7: fourth pulp extract treatment group).

Figure 4 is a measure of the effect of persimmon extract on the expression of MMP-9 in the atopic dermal animal model treated persimmon extract (1: no treatment group, 2: atopic dermatitis group, 3: atopic clear ointment treatment group, 4 : Primary pulp extract treatment group, 5: secondary pulp extract treatment group, 6: tertiary pulp extract treatment group and 7: fourth pulp extract treatment group).

5 is a measure of the effect of the persimmon extract on the expression of interleukin-4 in atopic dermal animal model treated with persimmon extract.

Figure 6 measures the effect of the persimmon extract on the expression of interleukin-13 in atopic dermatitis animal model treated with persimmon extract.

7 is a diagram showing the results of experiments measured by using a hematoxylin-Eosin (HE) staining method in the atopy-induced animal model treated with tannin (1: untreated group, 2: atopy Triggered group, 3: Atoclear ointment treated group and 4: tannin treated group).

Figure 8 is a measure of the effect of tannin on the expression of MMP-2 in tannin-treated atopy-induced animal model (1: no treatment group, 2: atopy-inducing group, 3: atopic clear ointment treatment group and 4: tannin) Treatment group).

Figure 9 is a measure of the effect of tannin on the expression of MMP-9 in the atopy-induced animal model treated with tannin (1: no treatment group, 2: atopy-induced group, 3: atopic clear ointment treatment group and 4: tannins) Treatment group).

Claims (10)

Persimmon containing tannin as an active ingredient ( Diospyros kaki Thunb.) Pharmaceutical composition for the treatment of immune-related diseases containing extracts or tannins as an active ingredient. The pharmaceutical composition of claim 1, wherein the immune related disease is selected from the group consisting of atopy, asthma or rhinitis. The pharmaceutical composition according to claim 1, wherein the persimmon ( Diospyros kaki Thunb.) Extract or tannin containing tannin as an active ingredient has a function of inhibiting the expression of MMP-2 or MMP-9. According to claim 1, Persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) The pharmaceutical composition, characterized in that the extract is prepared by the following steps: (a) crushing persimmon ( Diospyros kaki Thunb.), followed by C _3-6 lower alcohol, water, C _3-6 lower organic acid, C _3-6 lower alcohol ester, C _3-6 lower ketone and Extracting with a solvent selected from the group consisting of C _3-6 halogenated hydrocarbons; And (b) recovering the extract. According to claim 1, Persimmon ( Diospyros kaki Thunb.) Extract containing tannin as an active ingredient is Diospyros kaki Thunb.) Pharmaceutical composition, characterized in that the flesh extract. Diospyros kaki Thunb. Extract containing tannin as an active ingredient or a health food for improving immune-related diseases containing tannin as an active ingredient. The health food according to claim 6, wherein the immune-related disease is selected from the group consisting of atopy, asthma or rhinitis. According to claim 6, Persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extract or tannin (tannin) is a health food characterized in that it has a function of inhibiting the expression of MMP-2 or MMP-9. According to claim 6, Persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extract is a health food characterized in that it is prepared by the following steps: (a) Diospyros kaki Thunb.), And then the crushed, C _{3 -6} of a lower alcohol, water, halogenated hydrocarbons, C _{3 -6} lower organic acid, a lower alcohol ester of a C _{3 -6,} C _{3 -6} lower ketones and C _{3 -6} of Extracting with a solvent selected from the group consisting of: And (b) recovering the extract. According to claim 6, Persimmon containing the tannin as an active ingredient ( Diospyros kaki Thunb.) Extract Diospyros kaki Thunb.) Health food, characterized in that the flesh extract.

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