JP6562332B2 - Composition for suppressing IL-8 production from activated T cells - Google Patents

Description

  The present invention relates to a composition for suppressing IL-8 production from activated T cells, comprising a dopamine D2-like receptor agonist as an active ingredient.

  Helper T cells that play a central role in acquired immunity are classified into Th1 (type 1 helper T cells), Th2 (type 2 helper T cells), Th17 (type 17 helper T cells) and the like based on differences in cytokines produced. Is done.

  Conventionally, abnormalities in the Th1 / Th2 balance are considered to be involved in the development of various immune-related diseases. For example, the balance bias toward Th1 cells is rheumatoid arthritis, which is a chronic inflammatory disease, and organ-specific autoimmunity. Diseases (eg, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, glomerulonephritis, hepatitis, liver damage, autoimmune hemolytic anemia, leukopenia, thrombocytopenia, demyelinating disease, Hashimoto's thyroiditis, Malignant anemia, psoriasis) and the like, and balance bias to Th2 cells is thought to be involved in allergic diseases and many systemic autoimmune diseases. On the other hand, Th17 cells are involved in the exacerbation of autoimmune inflammation by producing IL-17 exclusively, and in particular, the aforementioned type 1 diabetes, inflammatory bowel disease, psoriasis, multiple sclerosis, and joints It is considered that rheumatism is strongly suspected to be caused by this deflection to Th17 (Non-patent Document 1).

  Various factors are involved in the acquired immune system in a complicated manner, and it is still unclear whether which immune-related disease is involved in Th1 bias, Th2 bias, or Th17 bias. Have already found that the action of dopamine (DA) is greatly involved in the Th1 / Th2 / Th17 differentiation induction mechanism via dendritic cells (Patent Document 1). Specifically, in this report, when an antagonist is allowed to act on dopamine D1-like receptors on dendritic cells, synthesis and storage of dopamine in dendritic cells is suppressed, resulting in Th17 of naive T cells. It has been shown that the induction of differentiation into cells or Th2 cells is suppressed and the induction of differentiation into Th1 cells is promoted. Furthermore, when an antagonist is allowed to act on a dopamine D2-like receptor on dendritic cells, synthesis and storage of dopamine in dendritic cells is promoted, and as a result, induction of differentiation of naive T cells into Th1 cells is suppressed. It has also been shown that induction of differentiation into Th2 cells is promoted.

  On the other hand, the inventors of the present invention have found that Korentoto (Chinese prescription containing ougonin as a main ingredient) suppresses the induction of Th17 cell differentiation, and berberine suppresses the induction of Th17 cell or Th1 cell differentiation. Have also been reported (Non-Patent Documents 2 to 4). However, all of these findings are intended to control the induction of differentiation from naive T cells to Th cells, and are not intended to control the functions of Th cells that have already differentiated and activated.

Patent No. 5442256

Batten, M et al. Interleukin 27 limit autoimmune encephalomyelitis by suppression the development of interleukin 17-production T cells. Nat Immunol. 2006. 7: 929-936. Rie Takagi et al., Th17-selective inhibitory action of Korento and improved action in neutrophilic airway inflammation model, clinical allergy 34: 66-68, 2014 Takagi, R.A. et al. Wogonin attendants ovalbuminantigen-induced neutrophic airway information by inhibiting Th17 differentiation. Int. J. et al. Inflamm. , Vol. 2014, Article ID 571508, 8 pages. Kawano, M .; et al. Berberine is a dopamine D1-, D2-like receptor antagonist and ameliorates experimentally induci- tively suppressing innate and adaptive. J. et al. Neuroimmunol. 289: 43-55, 2015.

  The present invention has been made in view of the above-described state of the art, and an object of the present invention is to provide a composition capable of acting on an activated Th cell dopamine receptor and controlling the function of the cell. is there.

  As a result of intensive studies to solve the above problems, the present inventor has found that tannic acid, gallic acid, and gallic esters of catechins have agonist activity with respect to the dopamine D2 receptor. .

  Moreover, the cytokine production of each Th cell was analyzed and the influence of the dopamine D2-like receptor agonist on the cytokine production was evaluated. The dopamine D2-like receptor agonist acts on the dopamine D2-like receptor in activated Th cells. The present inventors have found that the production of interleukin 8 (IL-8), an inflammation-related mediator known as a neutrophil chemotactic factor, is suppressed.

  Furthermore, the present inventor examined the effect of a dopamine D2-like receptor agonist using model animals of various diseases related to neutrophilic inflammation, and found that neutrophilic airway inflammation, psoriasis, ulcerative colon It was found that each animal model of inflammation and periodontal disease has an effect of treatment or improvement of the disease, and the present invention has been completed.

  Accordingly, the present invention relates to the use of a dopamine D2-like receptor agonist for suppressing IL-8 production in activated Th cells, and more specifically provides the following.

  (1) A composition for suppressing IL-8 production of activated helper T cells, comprising a dopamine D2-like receptor agonist as an active ingredient.

  (2) The composition according to (1), wherein the dopamine D2-like receptor agonist is tannic acid, gallic acid, catechins or gallic esters thereof, ropinirole, or pramipexole.

  (3) The composition according to (1) or (2), wherein the activated helper T cell is a Th1 cell or a Th17 cell.

  (4) The composition according to any one of (1) to (3), which is used for treatment or amelioration of neutrophilic inflammation.

  Neutrophilic airway inflammation including neutrophilic bronchial asthma, periodontal disease, psoriasis, severe atopic dermatitis, acne vulgaris, endometriosis, chronic sinusitis, and other various autoimmune diseases, etc. There are many pathological conditions mainly consisting of neutrophilic inflammation. However, no specific medicine has been known so far. Corticosteroids are a specific drug for eosinophilic inflammation, not a specific drug for neutrophilic inflammation. The composition of the present invention targets the dopamine D2-like receptor on activated Th cells and exerts an effect by a novel mechanism of suppressing IL-8 production of the cells. Such side effects are not considered to be a problem. Tannic acid, gallic acid, catechins or gallic acid esters thereof are natural ingredients contained in various plants and are particularly safe. ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to perform effectively and safely the treatment and improvement of the symptom (especially neutrophilic inflammation) resulting from the production of IL-8 from activated Th cells.

It is a graph which shows the result of having detected RC50 with respect to the dopamine D2 receptor of a tannic acid. It is the graph which quantified specific cytokine (IFNgamma, IL-5, or IL-17) production and IL-8 production in each Th cell clone, and showed the correlation. A graph showing the results of evaluating the effect on IL-8 production by coexisting dopamine D2-like receptor agonists (pramipexole and ropinirole) in a system in which peripheral blood mononuclear cells (PMBC) are co-cultured with Candida antigen. is there. It is a graph which shows the result of having evaluated the influence which tannic acid coexists in the system which co-cultures a peripheral blood mononuclear cell (PMBC) with a Candida antigen, and gives to IL-8 production. It is a graph which shows the effect of a dopamine D2-like receptor agonist in a neutrophilic airway inflammation model. Pramipexole and ropinirole were used as dopamine D2-like receptor agonists. It is a graph which shows the effect of a dopamine D2-like receptor agonist in a psoriasis model. As dopamine D2-like receptor agonists, A used pramipexole and tannic acid, and B used tannic acid and gallic acid. It is a graph which shows the effect (inhibition of a decrease in body weight) of a dopamine D2-like receptor agonist in an ulcerative colitis model. Ropinirole was used as a dopamine D2-like receptor agonist. It is a graph which shows the effect (inhibition of a decrease in body weight) of a dopamine D2-like receptor agonist in an ulcerative colitis model. Tannic acid was used as a dopamine D2-like receptor agonist. It is a graph which shows the effect (intestinal contraction inhibitory effect) of a dopamine D2-like receptor agonist in an ulcerative colitis model. Tannic acid was used as a dopamine D2-like receptor agonist. It is a graph which shows the effect of a dopamine D2-like receptor agonist in a periodontal disease model. Tannic acid was used as a dopamine D2-like receptor agonist.

  The present invention provides a composition for suppressing IL-8 production of activated helper T cells, comprising a dopamine D2-like receptor agonist as an active ingredient.

  The “dopamine receptor” has five subtypes, D1 to D5, and is generally known to have a function of coupling a G protein to send a signal into a cell. Among these, the dopamine D2 receptor, the dopamine D3 receptor, and the dopamine D4 receptor are collectively called “dopamine D2-like receptor”, and their activation promotes the degradation of intracellular cAMP. cAMP concentration decreases. The typical amino acid sequence of human-derived dopamine D2 receptor is NCBI Reference Sequence: NP_000786.1 and NCBI Reference Sequence: NP_05768.2, and the typical amino acid sequence of human-derived dopamine D3 receptor is NCBI. Reference Sequence Sequence: NP_000787.2 discloses a typical amino acid sequence of a human-derived dopamine D4 receptor in NCBI Reference Sequence: NP_0007888.2, respectively. “Dopamine D2-like receptor agonist” means a compound that binds to a dopamine D2-like receptor and activates such signal transduction, such as ropinirole (Requip), pramipexole (Biciflor), bromocriptine (Perlodel). ), Pergolide (Permax), cabergoline (Cabasar), rotigotine (New Pro) and the like, but are not limited thereto. In the present invention, since tannic acid, gallic acid, catechins and gallate esters thereof have been found to be dopamine D2 receptor agonists, these are also included in the “dopamine D2-like receptor agonist” of the present invention. included. Examples of catechins and gallate esters thereof include catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. Whether or not a certain compound is a dopamine D2-like receptor agonist can be evaluated, for example, by an assay using Ca concentration or cAMP concentration as an index, as described in this Example.

  In the present invention, “activated helper T cells” are helper T cells differentiated by recognizing a specific antigen via a T cell receptor, and include so-called effector T cells and memory T cells. Examples of “helper T cells” to which the present invention is applied include Th1 cells, Th2 cells, and Th17 cells, which can be distinguished by the production of specific cytokines. Specific cytokines include interferon γ (IFNγ) and IL-2 in Th1 cells, IL-4, IL-5, and IL-13 in Th2 cells, and in Th17 cells, IL-17 is mentioned. The helper T cells targeted for inhibiting IL-8 production by the composition of the present invention are preferably Th1 cells and Th17 cells.

  The composition of the present invention may be in the form of a pharmaceutical composition (pharmaceuticals, quasi drugs, veterinary drugs, etc.), food and drink, or a reagent used for research purposes (eg, in vivo experimental purposes).

  The composition of the present invention can be used for treatment or amelioration of symptoms caused by IL-8 production of activated T cells. Since IL-8 is an inflammation-related mediator known as a major neutrophil chemotactic factor, the composition of the present invention can be suitably used in the treatment or amelioration of neutrophilic inflammation. The composition of the present invention includes, for example, neutrophilic airway inflammation including neutrophilic bronchial asthma, periodontal disease, psoriasis, ulcerative colitis, severe atopic dermatitis, acne vulgaris, endometriosis , Treatment or amelioration of various diseases such as chronic sinusitis and other various autoimmune diseases (eg, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, nephritis), especially among the symptoms of these diseases It can be applied to the treatment or amelioration of spherical inflammation. Here, “treatment or improvement of neutrophilic inflammation” includes treatment or improvement of various symptoms or morphological changes caused by neutrophilic inflammation.

  When the composition of the present invention is used as a pharmaceutical composition, the dosage form is not particularly limited as long as it contains a dopamine D2-like receptor agonist as an active ingredient. The pharmaceutical composition of the present invention can be formulated into various dosage forms by known pharmaceutical methods.

  There is no restriction | limiting in particular as a dosage form of pharmaceutical composition, For example, it can select suitably according to the desired administration method, For example, oral solid agent (a tablet, a coated tablet, a granule, a powder, a capsule etc.) , Oral solutions (internal solutions, syrups, elixirs, etc.), external preparations (suppositories, ointments, patches, gels, creams, external powders, sprays, inhalants), injections (solutions, suspensions) Liquids, solid preparations for business use, etc.), oral preparations (gum, troches, sublingual tablets, buccal tablets, adhesives), oral sprays, oral semisolids, dentifrices, gargles, etc. Is mentioned.

  As an oral solid preparation, for example, an additive such as a binder, a disintegrant, a lubricant, a coloring agent, a flavoring / flavoring agent, and the like are added to a dopamine D2-like receptor agonist, It can be produced by a conventional method.

  Examples of the excipient include lactose, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicic acid and the like. Examples of the binder include water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl starch, methylcellulose, ethylcellulose, shellac, calcium phosphate, polyvinylpyrrolidone and the like. . Examples of the disintegrant include dry starch, sodium alginate, agar powder, sodium hydrogen carbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, and lactose. Examples of the lubricant include purified talc, stearate, borax, and polyethylene glycol. Examples of the colorant include titanium oxide and iron oxide. Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like.

  As an oral solution, for example, additives such as a taste-masking / flavoring agent, a buffering agent, and a stabilizer can be added to a dopamine D2-like receptor agonist and produced by a conventional method.

  Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like. Examples of the buffer include sodium citrate. Examples of the stabilizer include tragacanth, gum arabic, and gelatin.

  Examples of suppositories include dopamine D2-like receptor agonists, known suppository preparation carriers such as polyethylene glycol, lanolin, cocoa butter and fatty acid triglycerides, and interfaces such as TWEEN (registered trademark) as necessary. After adding an activator etc., it can manufacture by a conventional method.

  As the ointment, for example, a known base, stabilizer, wetting agent, preservative and the like may be blended with a dopamine D2-like receptor agonist and mixed by a conventional method.

  Examples of the base include liquid paraffin, white petrolatum, white beeswax, octyldodecyl alcohol, and paraffin. Examples of the preservative include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and the like.

  As the patch, for example, a cream, gel or paste as an ointment can be applied to a known support by a conventional method. Examples of the support include cotton, suf, woven fabric made of chemical fibers, non-woven fabric, soft vinyl chloride, polyethylene, polyurethane and other films, foam sheets, and the like.

  As an injection, for example, a pH regulator, a buffer, a stabilizer, a tonicity agent, a local anesthetic, etc. are added to a dopamine D2-like receptor agonist, and subcutaneous, intramuscular, intravenous, etc. are added by a conventional method. An injection for internal use can be produced.

  Examples of the pH adjuster and buffer include sodium citrate, sodium acetate, sodium phosphate and the like. Examples of the stabilizer include sodium pyrosulfite, EDTA, thioglycolic acid, thiolactic acid and the like. Examples of the isotonic agent include sodium chloride and glucose. Examples of the local anesthetic include procaine hydrochloride and lidocaine hydrochloride.

  A preparation to be applied to the oral cavity can also be formulated by a known pharmacological method depending on its properties.

  When the composition of the present invention is used as a pharmaceutical composition, one or two or more types effective for suppressing IL-8 production (preferably, treatment of neutrophilic inflammation) of activated helper T cells. Other ingredients can be blended. Moreover, you may use together with the other pharmaceutical composition effective for this objective.

  The administration target of the pharmaceutical composition is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include humans, mice, rats, cows, pigs, monkeys and the like. The administration method can be appropriately selected depending on the dosage form and the like, and examples thereof include oral, external use, and administration by injection. The dose can be appropriately selected according to the type, age, weight, sex, symptom, etc. of the administration subject. For example, the amount of dopamine D2-like receptor agonist as an active ingredient per day for a human adult, For example, an amount selected within the range of 0.04 to 500 mg is considered preferable. There is no restriction | limiting in particular also as administration frequency, According to the objective, it can select suitably, For example, the dosage per day may be administered once per day, or it divides into multiple times. May be. Moreover, you may administer 1 to 4 times a week instead of every day.

  When the composition of the present invention is used as a food or drink, the food or drink can be, for example, a health food, a functional food, a food for specified health use, a dietary supplement, a food for the sick, or a food additive. Specific examples of food and drink include liquid foods such as drinks, soups, milk drinks, soft drinks, tea drinks, alcoholic drinks, jelly drinks, functional drinks; oils such as edible oils, dressings, mayonnaise, margarines Products containing carbohydrates; Foods containing carbohydrates such as rice, noodles, and bread; Livestock processed foods such as ham and sausage; Fish processed foods such as kamaboko, dried fish, and salted vegetables; Vegetable processed foods such as pickles; Semis such as jelly and yogurt Solid foods; Fermented foods such as miso and fermented beverages; Various confectioneries such as Western confectionery, Japanese confectionery, candy, gums, gummi, frozen confectionery, ice confectionery; Retort products such as curry, sauce, Chinese soup; Instant soup, Examples include instant foods such as instant miso soup and foods compatible with microwave ovens. Furthermore, health foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly are also included.

  Manufacture of the food-drinks in this invention can be implemented with a manufacturing technique well-known in the said technical field. In food and drink, one or more components effective for suppressing IL-8 production (preferably improving neutrophilic inflammation) of activated helper T cells may be blended. Moreover, it is good also as multifunctional food / beverage products by combining with the other component which exhibits the function of this objective, or another functional food.

  The food / beverage ingestion target can be appropriately selected according to the purpose, and examples thereof include humans, mice, rats, cows, pigs, monkeys, and the like. The intake amount can be appropriately selected according to the type, age, weight, sex, symptom, etc. of the intake subject, for example, as an amount of dopamine D2-like receptor agonist as an active ingredient per day for a human adult, For example, an amount selected within the range of 0.04 to 500 mg is considered preferable. The intake frequency can be appropriately selected according to the purpose. For example, the intake amount per day may be taken once a day, or may be taken divided into a plurality of times. Also, it may be taken 1 to 4 times a week instead of every day.

  The composition of the present invention may be in the form contained in a particular device. Accordingly, the present invention provides a device comprising the above composition. There is no restriction | limiting in particular in the form of the said instrument, It changes according to the objective of the composition of this invention. For example, for the purpose of treating or improving neutrophilic inflammation in periodontal disease, the composition of the present invention is in a form contained in dental floss, interdental brush, sponge product for interdental brush, toothpick, etc. obtain.

  The product of the composition of the present invention (pharmaceuticals, quasi-drugs, veterinary drugs, food and drink, reagents, instruments containing these, etc.) or instructions thereof include, for example, IL-8 production of activated helper T cells The indication that it is used for the treatment or improvement of symptoms (preferably, neutrophilic inflammation) caused by or for the suppression of IL-8 production by activated helper T cells is attached. It can be a thing.

  Here, “labeled product or instructions” means that the product body, container, packaging, etc. are marked, or instructions, package inserts, promotional materials, or other printed materials that disclose product information. It means that the display is attached to.

  EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not limited to a following example.

[Example 1] Action of tannic acid on dopamine receptors Calcium concentration is changed in response to specific dopamine receptors (dopamine D1, dopamine D2, dopamine D4 and dopamine D5 receptors). The effect of tannic acid on each dopamine receptor was examined by “GPCRProfiler” (registered trademark) service using a cell line to be measured and an intracellular Ca concentration measurement system using FLIPR (Eurofins). The% agonist activity indicates the degree to the maximum response of dopamine, and the% antagonist activity indicates the degree of inhibition of dopamine on EC80.

  As a result, tannic acid was found to have agonist activity at the dopamine D2 receptor, and agonist activity and antagonist activity at the dopamine D4 receptor and dopamine D5 receptor (Table 1).

  The determination of RC50 for dopamine D2 receptor of tannic acid was analyzed using a cell line that specifically responds to dopamine D2 receptor stimulation and changes cAMP concentration (DiscoverX). Specifically, it shows the degree when the maximum value by which dopamine suppresses the increase in cAMP by forskolin is 100%. The tannic acid RC50 for the dopamine D2 receptor was 2.23 μM (FIG. 1). The RC50 of dopamine itself is 0.0013 μM.

  From the above, it was suggested that tannic acid is a partial agonist having antagonist activity for dopamine D4 receptor and dopamine D5 receptor. That is, in the absence of dopamine, agonist stimulation is applied to dopamine D4 receptor and dopamine D5 receptor, but in the presence of dopamine, only dopamine signals via dopamine D4 receptor and dopamine D5 receptor are suppressed. In the field of physiological immune response, since dopamine produced from immunocompetent cells exists, it is considered that tannic acid relatively enhances the signal via D2R and induces a decrease in intracellular cAMP.

[Example 2] Inhibition of IL-8 production in activated T cells by dopamine D2-like receptor agonist Next, the effect of tannic acid on acquired immune inflammation, particularly neutrophilic inflammation, was analyzed. A plurality of alloreactive Th1 / Th2 / Th17 cell clones were established, and IFNγ, IL-5, IL-17 and IL-8 produced by them were quantified. The results are shown in FIG. It was revealed that IL-8 production was positively correlated with Th1 cytokine (IFNγ) production and Th17 cytokine (IL-17) production. The correlation values are as follows.

  Correlation between IL-8 and IFNγ (FIG. 2 left): r = 0.3172, P <0.01, correlation between IL-8 and IL-5 (center of FIG. 2): r = −0.05216, P = ns (Not significant), correlation between IL-8 and IL-17 (FIG. 2 right): r = 0.5485, P = 0.01.

  When human PBMC are stimulated with Candida antigen, production of IFNγ, IL-17, and IL-8 is observed. Therefore, pramipexole and ropinirole, which are known dopamine D2-like receptor agonists, were added to the system, and the IL-8 concentration in the supernatant after 7 days was measured. As a result, suppression of IL-8 production was observed (FIG. 3).

  When a similar experiment was performed with tannic acid, tannic acid suppressed PBMC polyclonal IL-8 production (FIG. 4). There was no significant difference in IFNγ production.

[Example 3] Effect of dopamine D2-like receptor agonist in neutrophilic airway inflammation model Each drug (water, pramipexole, ropinirole) was orally administered to DO11.10 mice 3 times a week for 6 weeks (0 .3 mg / kg / day). Thereafter, the mice were sacrificed the next day after inhalation of ovalbumin (OVA) for 3 consecutive days, BALF (bronchoalveolar lavage fluid) was collected, and the number of neutrophils was counted. As a result, since the dopamine D2-like receptor agonist decreased the neutrophil count, it was proved to be effective against the neutrophilic airway inflammation model (FIG. 5).

[Example 4] Activity of tannic acid-related compound on D2 receptor The agonist / antagonist activity of tannic acid-related compound was measured using GPCR Biosensor Assay (for the activity of tannic acid, discovery services of eurofins, for the activity of other molecules). Using LeadHunt discovery services (DiscoverX, Inc.), the amount of cAMP was measured as an index. Since gallic acid is sparingly soluble in water, it was dissolved in DMSO and added to the assay system. Table 2 shows the results calculated by standardization with respect to the maximum and minimum responses.

  The biochemical data of gallic acid shows only weak agonist activity, which is thought to be affected by precipitation in an aqueous solvent by dissolving in DMSO and adding it to the assay system.

[Example 5] Effect of dopamine D2-like receptor agonist in psoriasis model C57BL / 6 mice were treated with imiquimod (IMQ) cream alone and IMQ cream mixed with dopamine D2-like receptor agonist (three types) under the mouse ear. Then, the thickening was observed. On the 8th day from the start, significant suppression of auricular thickening was observed in the administration group of cream containing 10 mg of tannic acid or 10 mg of gallic acid (per 250 mg of cream) compared to IMQ cream alone (FIG. 6).

[Example 6] Effect of dopamine D2-like receptor agonist in ulcerative colitis model (1) Inhibition of body weight loss 4% dextran sulfate sodium (DSS) containing 0.114 mg / ml ropinirole was applied to C57BL / 6J mice. Free drinking water was administered (about 5 ml / day). This dose corresponds to about 28 mg / kg. As a result, on the fourth day from the start, a significant reduction in body weight was observed in the ropinirole administration group compared to the control group (FIG. 7A). Further, when a similar experiment was conducted with 4% sodium dextran sulfate (DSS) containing tannic acid at 10 mg / ml, significant reduction in body weight was observed with tannic acid (FIG. 7B).
(2) Intestinal contraction inhibitory effect 4% dextran sulfate sodium (DSS) containing tannic acid at each concentration (1, 5, 10 mg / ml) was administered to C57BL / 6J mice with free drinking water. As a result, on the seventh day from the start, significant intestinal contraction suppression was observed in the group administered with 5 or 10 mg / ml tannic acid as compared to the control group (FIG. 8).

[Example 7] Effect of dopamine D2-like receptor agonist of tannic acid in periodontal disease model induced by immunostimulant carrageenan PBS, 1% carrageenan, 1% carrageenan + 1% The operation of inserting 2-3 mm silk thread soaked in tannic acid was performed once a week for 3 weeks (n = 4). When the alveolar bone resorption by μCT was measured after 4 weeks from the start, the alveolar bone resorption induced by 1% carrageenan was significantly suppressed by 1% tannic acid (FIG. 9).

  As described above, the composition of the present invention can be used as a pharmaceutical or food / drink for treating or ameliorating symptoms caused by IL-8 production of activated helper T cells, and IL of activated helper T cells. It can be used as a reagent for suppressing -8 production.

Claims (1)

An active ingredient tannic acid, the composition for the ulcerative colitis or for use in the treatment or amelioration of psoriasis.