KR20130035425A - A composition for the prevention and treatment of inflammatory disease comprising hs1792 - Google Patents

Abstract

PURPOSE: A composition containing HS1792(6-(3-hydroxyphenyl)-2-naphthol) for preventing or treating inflammatory diseases is provided to suppress inflammatory cytokine generation and to relieve arthritis occurrence and development. CONSTITUTION: A composition for preventing or treating inflammatory diseases contains HS1792(6-(3-Hydroxyphenyl)-2-naphthol) or a pharmaceutically acceptable salt thereof as an active ingredient. The inflammatory diseases are selected from the group consisting of dermatitis, allergy, atopy, asthma, conjunctivitis, periodontitis, rhinitis, tympanitis, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoid, ventilation, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis of shoulder, tendinitis, vaginitis, peritendinitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome, multiple sclerosis, and acute and chronic inflammatory diseases.

Description

A composition for the prevention and treatment of inflammatory disease comprising HS1792 as an active ingredient

The present invention relates to a composition for preventing or treating inflammatory diseases. More specifically, 6- (3-hydroxyphenyl) -2-naphthol (6- (3-Hydroxyphenyl) -2-naphthol) containing an active ingredient for preventing or treating inflammatory diseases, and improving and preventing inflammatory diseases It relates to a nutraceutical.

Inflammation is one of tissue damage, an external stimulus, or a protective response of biological tissues to various infectious agents. Enzyme activation, inflammatory mediator secretion, cell infiltration due to organic interaction of various inflammatory mediators and various immune cells in blood vessels and body fluids And a series of complex pathologies, including fluid effusion, circulatory disorders, tissue degeneration and hyperproliferation. In the inflammatory process, macrophages initially gather into the wound and attack the invading bacteria, and then plasma builds up in the wound and increases blood flow, causing external symptoms such as fever, erythema, edema, and pain. . If these inflammatory reactions occur continuously or excessively, the disease progresses to the main pathology of the disease (sensitized allergic disease, chronic inflammatory disease) and causes serious abnormal disorders.

Various biochemical phenomena are involved in the cause of inflammation in living body. Macrophage (macrophage) is a cell with a variety of functions to produce various cytokines and nitric oxide (NO) by chemical stimulation plays an important role in the inflammatory response. Inducible nitric acidase, especially expressed by cytokine stimulation such as lipopolysaccharide (LPS), interferon-γ, and tumor necrosis factor-α (TNF-α) in macrophages oxide synthase (iNOS) produces large amounts of NO over long periods of time. This oxidative stress is known to promote NFκB activity, a transcription factor of the inflammatory response inhibited by IκB. Activated NFκB is known to migrate to the nucleus and stimulate the expression of genes that induce inflammatory responses, such as iNOS, COX-2 and several cytokines such as interleukin-1β and IL-1β or TNF-α. Inhibition of these factors is known to inhibit the inflammatory response (Baeuerle et al., Annu. Rev. Immunol., 12: 141-179, 1994). Therefore, the search for a substance that inhibits the production of TNF-α, NO, prostaglandin or IL-1β may prove to be an effective substance for inflammatory diseases such as edema or dermatitis.

Non-steroidal anti-inflammatory drugs (NSAIDS), a widely used drug for the treatment of most inflammatory diseases, are produced from prostaglandin from arachidonic acid called cyclooxygenase (COX). By inhibiting the enzyme activity involved in the biosynthesis of the drug, it exhibits anti-inflammatory action, which causes serious side effects such as gastrointestinal disorders, liver disorders, and renal disorders in addition to the main therapeutic effects, and thus is restricted in long-term use (Rajakariar R et. al. 2006). Therefore, the development of a new anti-inflammatory analgesic that is excellent in anti-inflammatory efficacy without any difficulty for long-term use with little side effects is widely required, which is also a reason for the recent active research on material development through verification of efficacy from natural resources.

Accordingly, the inventors of the present application have been eager to develop an agent for inflammatory diseases without toxicity and side effects. As a result, the inventors have developed effective compositions for preventing and treating inflammatory diseases.

Accordingly, it is therefore an object of the present invention to provide a pharmaceutical composition for the prevention and treatment of inflammatory diseases.

It is also an object of the present invention to provide a dietary supplement for the improvement and prevention of inflammatory diseases.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of inflammatory diseases containing 6- (3-Hydroxyphenyl) -2-naphthol (HS1792) or a pharmaceutically acceptable salt thereof as an active ingredient. to provide.

The inflammatory diseases include dermatitis, allergy, atopic dermatitis, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia (fibromyalgia) ), Psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis, tendinitis, hay salt, periarthritis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis, and acute and chronic inflammatory diseases It may be either, preferably osteoarthritis or rheumatoid arthritis.

The pharmaceutical composition may inhibit proinflammatory cytokine production in synovial tissue, alleviate the development and deepening of arthritis, or inhibit inflammatory cytokines in blood.

The present invention also provides a dietary supplement for improving and preventing inflammatory diseases, including 6- (3-Hydroxyphenyl) -2-naphthol (HS1792).

The inflammatory diseases include dermatitis, allergy, atopic dermatitis, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia (fibromyalgia) ), Psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis, tendinitis, hay salt, periarthritis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis, and acute and chronic inflammatory diseases It may be either, preferably osteoarthritis or rheumatoid arthritis.

Inflammatory disease agent of the present invention inhibits proinflammatory cytokine production in synovial tissue, alleviates the onset and deepening of arthritis, and inhibits inflammatory cytokines in the blood, which is effective for treating and preventing inflammatory diseases. It can be used as a composition and dietary supplement for improvement.

Figure 1 shows the chemical structural formula of the HS1792 of the present invention.
Figure 2 shows the mRNA expression of inflammation-related genes after treatment of TNF-alpha and HS1792 in synovial cells.
Figure 3 is a graph showing the amount of inflammation-associated cytokines after treatment with TNF-alpha and HS1792 in synovial cells.
4 is a graph showing the inhibition of the incidence of arthritis due to the administration of HS1792 in the collagen-induced arthritis mouse model.
FIG. 5 is a graph measuring the effect of treating foot edema in a collagen-induced arthritis mouse model by HS1792 by index grade (scoring).
6 is a macroscopic view of the foot of a mouse administered HS1792 to the abdominal cavity of normal mice, collagen-induced arthritis mice and collagen-induced arthritis mice, respectively.
7 is a micro-computed tomography scan and three-dimensional reconstruction of the structure of the knee and hind paws of the HS1792-administered mice in the normal, collagen-induced arthritis and collagen-induced arthritis mice One image is a picture.
8 is a photograph of the knee cross-section of the mice treated with HS1792 in the abdominal cavity of normal mice, collagen-induced arthritis mice and collagen-induced arthritis mice.
9 is a graph of histopathological analysis of the degree of inflammation of normal mice, collagen-induced arthritis mice, and mice administered HS1792 to the abdominal cavity of collagen-induced arthritis mice.
Figure 10 shows the inflammatory cytokines TNF-alpha, IL-1beta, IL-6, IFN-gamma, MCP-1 in the serum of normal mice, collagen-induced arthritis mice and mice administered HS1792 to the collagen-induced arthritis mice intraperitoneally. And it is a graph showing the concentration of IL-17.

The present invention is for the prevention and treatment of inflammatory diseases containing 6- (3-hydroxyphenyl) -2-naphthol (6- (3-Hydroxyphenyl) -2-naphthol) or a pharmaceutically acceptable salt thereof as an active ingredient. It provides a pharmaceutical composition.

In the present invention, "HS1792" is a resveratrol derivative having a chemical formula of 6- (3-Hydroxyphenyl) -2-naphthol, a molecular formula of C ₁₆ H ₂ O ₂ , molecular weight is 236.0837. The chemical structure of the material is shown in FIG. "Resveratrol" is a natural substance found in herbs, grape skins, nuts and red wine.

In the present invention, pharmaceutically acceptable salts of 6- (3-hydroxyphenyl) -2-naphthol (6- (3-Hydroxyphenyl) -2-naphthol) are as defined above, unless otherwise indicated. Salts of acidic or basic groups which may be present in compounds of the structure shown in 1. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate, dihydrogen Phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate), and p-toluenesulfonate (tosylate) salts, and methods or preparations for preparing salts known in the art It can be prepared through the process.

In the present invention, "inflammatory disease" is a dermatitis, allergy, atopic, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus , Fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis, tendonitis, hay salt, peritonitis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis or acute and chronic inflammatory diseases , Preferably osteoarthritis or rheumatoid arthritis, most preferably rheumatoid arthritis.

The term "prevention" means any action that inhibits or delays inflammation by administration of the composition. In addition, the "treatment" means any action that improves or advantageously changes the symptoms of inflammation by administration of the composition.

In addition, the pharmaceutical composition may inhibit proinflammatory cytokine production in synovial tissue, alleviate the onset and deepening of arthritis, or inhibit inflammatory cytokines in blood.

The HS1792 may be included in 0.001 to 50% by weight, preferably 0.01 to 20% by weight of the total pharmaceutical composition. In addition, the HS1792 may adjust the content so that an appropriate amount per 1 kg of the individual to which the pharmaceutical composition is administered in the whole pharmaceutical composition can be administered. For example, when the subject to be administered is human, the HS1792 may be administered in a pharmaceutical composition so as to be administered in an amount of 0.0001 to 500 mg / kg, preferably 0.001 to 500 mg / kg, more preferably 0.001 to 300 mg / kg. The amount included can be controlled.

The pharmaceutical composition of the present invention does not increase the efficacy, but may further include ingredients that are commonly used in the pharmaceutical composition to improve the smell, taste, time and the like. The composition may further comprise inorganic or organic additives such as vitamins B1, B2, B6, C, E, niacin, carnitine, betaine, folic acid pantothenic acid, biotin, zinc, iron, calcium, chromium, magnesium, As shown in FIG. In addition, the composition may include a substance having a prophylactic or therapeutic activity against inflammatory diseases used alone or previously used.

The pharmaceutical composition of the present invention comprises a pharmaceutically acceptable carrier and can be formulated for human or veterinary use for oral or parenteral use. When the composition of the present invention is formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants can be used. Solid form preparations for oral administration include tablets, pills, powders, granules and capsules, which may contain at least one excipient such as starch, calcium carbonate ), Sucrose or lactose, and gelatin. In addition to simple excipients, lubricants such as magnesium, styrene, and talc may be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions and syrups, and various excipients such as wetting agents, sweetening agents, fragrances and preservatives in addition to commonly used simple diluents such as water and liquid paraffin . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. As the non-aqueous solvent and suspending solvent, vegetable oils such as propylene glycol, polyethylene glycol and olive oil, injectable esters such as ethyl oleate and the like can be used.

The pharmaceutical composition of the present invention can be administered to an individual to prevent or treat an inflammatory disease. As used herein, the term “individual” has an inflammatory disease or complications arising therefrom, and horses, sheep, and pigs, including humans with diseases in which symptoms can be improved by administering the pharmaceutical composition of the present invention. , Mammals such as goats and dogs.

As used herein, the term “administration” means introducing a pharmaceutical composition of the invention to a subject in any suitable manner. The route of administration may be oral or parenteral via any general route so long as it can reach the desired tissue. In addition, the pharmaceutical composition of the present invention may be administered by any device that allows migration to target cells.

The composition of the present invention is administered in a pharmaceutically effective amount. The term " pharmaceutically effective amount " as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dosage level will vary depending on the sex, age, The activity of the compound, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. It may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art. The administration method of the composition containing the compound manufactured by the manufacturing method of this invention, oral administration or intravenous administration is preferable. Dosage levels for a particular patient may vary depending on gender, age, health condition, diet, time of administration, method of administration, drug mixture and severity of disease.

The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the treatment of inflammatory diseases.

In addition, the present invention provides a functional food for the improvement and prevention of inflammatory diseases, including 6- (3-Hydroxyphenyl) -2-naphthol (HS1792), the inflammatory diseases are dermatitis, allergy, atopic, asthma, conjunctivitis, periodontitis , Rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis, tendinitis, Hay salt, periarthritis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis or acute and chronic inflammatory diseases, preferably osteoarthritis or rheumatoid arthritis, most preferably rheumatoid arthritis.

Food composition comprising 6- (3-Hydroxyphenyl) -2-naphthol (HS1792) of the present invention may be added to health food for the purpose of preventing or improving inflammatory diseases. When the composition of the present invention is used as a food additive, the composition can be added as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, in the manufacture of food or beverages the compositions of the invention are added in an amount of up to 15% by weight, preferably up to 10% by weight relative to the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, it may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.

There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.

In the case of beverages, various flavors or natural carbohydrates may be added as an additional ingredient such as ordinary beverages. Such natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like . The proportion of the natural carbohydrate is generally about 0.001 to 0.4 g, preferably about 0.002 to 0.03 g per 100 ml of the food composition of the present invention.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. In addition, the food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components may be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.001 to 0.1 parts by weight per 100 parts by weight of the food composition of the present invention.

Hereinafter, the present invention will be described more specifically based on examples. It will be apparent to those skilled in the art that the embodiments are only for describing the present invention in more detail and that the scope of the invention is not limited by these embodiments in accordance with the gist of the present invention.

< Example 1  > Selection and treatment of experimental animal model

DBA1 / J Male strain 20-25g mice were purchased from Central Labs and quarantined for 2 weeks and cultivated for purification. Only healthy animals showing adaptability were used for the experiment. This experiment was conducted in the SPF (specific pathogen free) animal breeding room at Yangsan Pusan National University Hospital Experimental Animal Center with a breeding environment set at a temperature of 18-22 degrees, a relative humidity of 40-60%, and an illumination time of 12 hours (day and night cycles). , All mice were freely given solid feed for experimental animals and sterilized tap water.

< Example 2 > For mouse intraperitoneal administration HS1792  Injection preparation

HS1792 is a resveratrol derivative having the formula 6- (3-Hydroxyphenyl) -2-naphthol, having the molecular formula C16H2O2 and a molecular weight of 236.0837. The chemical structure of the material is shown in FIG.

Injectable solution for treating arthritis according to the present invention is prepared by diluting HS1792 in an amount required by using an electronic balance, dissolved in DMSO, and diluted in sterilized PBS to 10% DMSO. This injection was injected into the abdominal cavity of immunized collagen-induced arthritis mice at a total of 12 injections for 3 weeks at intervals of 5 mg / kg once every two days.

< Example 3 > Preparation of Collagen-Induced Arthritis Mouse Model

Collagen-induced arthritis mouse model experiment was conducted to investigate the therapeutic effect of HS1792.

Bovine type 2 collagen was homogeneously emulsified using a T-connector connected to a 3 ml syringe while cooling with Freund's adjuvant on ice. The emulsified collagen solution was injected intradermally into the tail base of 6-week-old DBA1 / J mice to administer an immunogen. On day 21 after primary immunization, bovine type 2 collagen was mixed with emulsified Freund's adjuvant and emulsified, followed by intradermal injection to the base of the tail to induce a second immunization (boosting) reaction. Symptoms began to appear gradually, and the clinical disease index of arthritis was determined. Visual observation of arthritis lesions was performed using the following score. 0: no swelling and redness, 1: slight redness and swelling of the ankle joint, 2: ankle joint redness and swelling distinct, 3: redness, including finger joints, severe swelling, 4: all areas of the joint Severe swelling throughout. Therefore, the best score for joint lesion was 4 per leg, and the best disease index was 16 for the left and right forefoot and hind foot per mouse.

< Example 4 > Arthritis Index Comparison by Visual Observation

After the second immunization, the front and rear feet of the mouse were visually observed at two-day intervals to confirm whether arthritis due to inflammation occurred.

< Experimental Example 1 > HS1792 of proinflammatory cytokine  Inhibitory effect

Fibroblast-like synoviocytes obtained during surgery in arthritic patients were collected and cultured and stimulated with TNF-alpha to increase the production of proinflammatory cytokine. At this time, HS1792 was treated to inhibit the transcription of proinflammatory mediators such as IL-6, IL-8 and MCP-1 using reverse transcriptase PCR (FIG. 2).

As a result, HS1792 was confirmed by the ELISA method that the production of IL-6, IL-8 and MCP-1 significantly decreased statistically (Fig. 3).

< Experimental Example 2 > Effect of Arthritis Treatment Using Collagen-Induced Arthritis Mouse Model

Three weeks after the first induction of immune response, HS1792 was administered for three weeks at two-day intervals. After selecting 8 mice per group, HS1792 was administered by intraperitoneal injection at 5 mg / kg in 10% DMSO. In the vehicle-treated group, only 10% DMSO was injected intraperitoneally. It then monitors the progression of arthritis and includes gross findings such as erythema and joint swelling at the joint site, histological findings such as hyperplasia of synovial cells at the joint site, cartilage and bone damage, and cytokine levels associated with inflammation. Molecular biological findings were examined to determine the extent of arthritis. HS1792 showed no toxic signals and no lethality was observed.

When the incidence of arthritis was examined based on the degree of swelling, the incidence of arthritis was 100% in the vehicle-treated group, whereas the HS1792-administered group was 50-60%. As a result, it was confirmed that HS1792 of the present invention reduces the incidence of arthritis (FIG. 4).

When assessing the degree of arthritis intensities, the progression of arthritis at the ankle site was judged by gross findings such as swelling of the joint area, and the treatment effect of arthritis over time was determined by the incidence of arthritis and the clinical arthritis score of arthritis. index). In addition, as a result of examining the arthritis progress index of the mouse, it was confirmed visually that the HS1792 administration group significantly decreased the arthritis progression index compared to the vehicle administration group (FIGS. 5 and 6).

< Experimental Example 3 > Arthritis Index Comparison by Visual Observation

In order to analyze cartilage and bone tissues of mice with arthritis three-dimensionally, the knee joints and hind feet of the mice were photographed with a micro-computed tomography scan and three-dimensional reconstruction with a software program.

As a result, the knee joint and hind paw of the vehicle-administered mouse showed typical arthritis of cartilage and bone loss and deformity. The HS1792-treated mouse showed similar findings to normal mice. It was confirmed (FIG. 7).

< Experimental Example 4 > Arthritis Index Comparison by Visual Observation

4-1: How to measure histopathological arthritis intensification

The most important of the pathologies of arthritis, in particular rheumatoid arthritis, can be summarized as the hyperproliferation of the joint synovial cells and the irreversible destruction of the cartilage tissue resulting from the overgrowth of the synovial cells and the progression of cartilage damage. Physiological analysis is the most valid.

Knee tissues of normal mice, collagen-induced arthritis mice and mice administered HS1792 to collagen-induced arthritis were isolated and fixed in 10% neutral buffered formalin (NBF) fixative, and calcium removal was performed using 10% EDTA solution. After decalcification, it was embedded in paraffin. Thereafter, 4 um tissue sections were prepared, and trichrome staining (bone staining) and Safranin-O staining (cartilage staining) were performed (FIG. 8).

As a specific method of determining or measuring the indices for measuring the degree of arthritis intensification, histological analysis was performed by separating knee joints of the vehicle-administered group and the HS1792-administered group. When trained researchers did not know which animals were given a vehicle or medication, the incidence and severity of arthritis was observed in Trichrome and Safranon-O stained images, indicating synovial inflammation, bone erosion, cartilage destruction, Four types of infiltration of immune cells were judged by the evaluation criteria of 0 to 4 (FIG. 9).

As a result, the HS1792 administration group was found to significantly relieve synovial tissue inflammation, bone erosion, cartilage cell destruction and immune cell infiltration compared to the vehicle.

4-2: Inflammation using molecular biological analysis Intensity  Measure

The concentration of inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, INF-gamma, MCP-1 and IL-17) in mouse blood was measured using ELISA method.

As a result of the investigation, the levels of TNF-alpha, IL-1beta, IL-6, IFN-gamma, MCP-1 and IL-17 were significantly decreased in the HS1792 group compared with the vehicle group (FIG. 10). .

In order to confirm the therapeutic effect of arthritis using HS1792, as a result of testing the therapeutic effect on arthritis using the collagen-induced arthritis mouse model of the present invention, the HS1792-administered group also reduced the incidence of arthritis compared to rheumatoid arthritis mice. In patients with arthritis, the degree of swelling of the ankle joint was significantly reduced. In addition, the histological findings of the knee joint region was significantly reduced damage to cartilage tissue compared to rheumatoid arthritis mice, it was confirmed that it is effective in suppressing and treating the development of arthritis of the present invention. The solution used for intraperitoneal administration was 10% DMSO mixed with PBS.

In particular, when the HS1792 of the present invention is administered compared to rheumatoid arthritis mice, inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IFN-gamma, etc.), which are known to be closely involved in the progression of arthritis, are suppressed. Could confirm.

Claims (7)

Pharmaceutical composition for the prevention and treatment of inflammatory diseases containing 6- (3-hydroxyphenyl) -2-naphthol (6- (3-Hydroxyphenyl) -2-naphthol) or a pharmaceutically acceptable salt thereof as an active ingredient .
The method of claim 1, wherein the inflammatory disease is dermatitis, allergy, atopic, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever , Lupus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis, tendonitis, hay salt, peritonitis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis, and acute and chronic inflammatory diseases A pharmaceutical composition for the prevention and treatment of inflammatory diseases, characterized in that any one selected from the group consisting of.
The pharmaceutical composition of claim 2, wherein the inflammatory disease is osteoarthritis or rheumatoid arthritis.
The method of claim 1, wherein the pharmaceutical composition inhibits proinflammatory cytokine production in synovial tissue, alleviates the onset and deepening of arthritis, or prevents inflammatory cytokines in the blood. Therapeutic pharmaceutical composition.
A dietary supplement for the improvement and prevention of inflammatory diseases, including 6- (3-hydroxyphenyl) -2-naphthol (6- (3-Hydroxyphenyl) -2-naphthol).
The method of claim 5, wherein the inflammatory disease is dermatitis, allergy, atopic, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever , Lupus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, periarthritis, tendonitis, hay salt, peritonitis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis, and acute and chronic inflammatory diseases Functional food for improvement and prevention of inflammatory diseases, characterized in that any one selected from the group consisting of.
The health functional food for improving and preventing inflammatory diseases according to claim 6, wherein the inflammatory disease is osteoarthritis or rheumatoid arthritis.

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