KR20110066263A - Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of eucommia ulmoides as effective component - Google Patents

Abstract

PURPOSE: A pharmaceutical composition containing Eucommia ulmoides extract is provided to ensure anti-inflammation and to develop a agent for preventing and treating rheumatoid arthritis. CONSTITUTION: An Eucommia ulmoides extract has anti-inflammatory activation and osteoclast suppression effect. A pharmaceutical composition for preventing or treating rheumatoid arthritis contains the Eucommia ulmoides extract as an active ingredient. The Eucommia ulmoides extract is a hot water extract of Eucommia ulmoides bark. A health food for preventing or treating rheumatoid arthritis contains the Eucommia ulmoides extract as an active ingredient.

Description

Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis containing extracts of Eucommia ulmoides as effective component}

The present invention relates to a pharmaceutical composition and a health food composition for preventing or treating rheumatoid arthritis, which contains the worm extract as an active ingredient. More specifically, the worm extract having an anti-inflammatory activity and inhibitory effect on osteoclasts, the extract as an active ingredient It relates to a pharmaceutical composition for preventing or treating rheumatoid arthritis, and to a health functional food for preventing or improving rheumatoid arthritis containing the extract as an active ingredient.

Inflammation is a bacterium-derived abscess that infiltrates tissues with purulent fungi, and white blood cells actively devour the resulting leukocytes, tissues that have been injured by bacteria, and cell debris. It refers to the pathological condition of the place, and the anti-inflammatory effect is to suppress the growth of invading bacteria by antibacterial agents, or to activate the macrophage that detects foreign substances measured during the abscess, and to increase the ability to digest and excrete them by abscesses. It means that the treatment process is accelerated.

In general, an inflammatory reaction is a defense process of a living body that attempts to repair and repair the damaged area when an invasion that causes some organic change in a living cell or tissue is applied. Therefore, such a series of reactions include local blood vessels, various tissue cells of body fluids, immune-involved cells, and the like.

To date, anti-inflammatory substances have therapeutic effects only in acute inflammation, but in chronic inflammation such as rheumatoid arthritis, it is reported that only the primary inflammatory phenomenon is alleviated, and immunological therapeutic effects cannot be expected. Recently, studies on hydroxy-eicosatetraenoic acid (HETE), leukotriene B4, and leukotriene C4 have been conducted, which has some effects on chronic inflammation (Huskisson. ED et al. Inflammation). , Mechanism and Treatment, MTP, Lancaster, England, p. 55 (1980)).

The bones of the human body are a very dynamic organ that maintains homeostasis by breaking down little by little each day and filling it with new bone in the amount broken down. Osteoblasts that break down bone (Osteoclast) and osteoblasts that regenerate bone maintain homeostasis, RANKL (Receptor Activator of NF-κB Ligand) is an inflammatory precursor protein and osteoclast surface receptor protein. Increased activity of osteoclasts, which absorb bones, promotes bone breakdown, thinner and more easily broken osteoporosis, and when osteoblast activity increases, bone density increases with bone density. Or osteoporosis will occur. Thus, osteoclast differentiation and increased activity result in bone destruction such as periodontitis, osteoporosis and arthritis.

Various oral therapeutics have been used as a pharmacotherapy for rheumatoid arthritis, but side effects due to drugs have been reported, and the types of substances for the treatment of rheumatoid arthritis from natural products are limited, which is a safe substance for treating rheumatoid arthritis from natural products. Research on development is required.

Eucommia ulmoides ) is a deciduous tree belonging to the genus Eucommiaceae. It is native to Sichuan , China , and is a rare tree belonging to the genus 1 and 1 genus. The pharmacological action of the larvae leads to direct dilation of vascular smooth muscle, lowering blood pressure, anti-aging and strengthening blood cholesterol levels. The larva leaves increase coronary blood flow. In addition, it enhances the adrenal cortex hormone of the animal and shows anti-inflammatory action, and it shows the suppression and enhancement of cellular immunity by regulating calming analgesic and body immune function. In addition, the bleeding time is shortened, diuretic action is also shown, there are anti-allergic action and uterine contraction action.

Korean Patent Publication No. 2001-0018321 discloses a health food composition for rheumatoid arthritis patients, and Korean Patent Publication No. 2005-0078080 discloses a pharmaceutical composition for treating arthritis and a method of manufacturing the same.

The present invention was derived by the above requirements, the present invention has completed the present invention by identifying the efficacy of preventing or treating arthritis of the worms extract having anti-inflammatory activity and osteoclast inhibitory effect in view of these points. .

In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of rheumatoid arthritis, containing as an active ingredient a worm extract having anti-inflammatory activity and osteoclast inhibitory effect.

The present invention also provides a health functional food for preventing or improving rheumatoid arthritis, which contains as an active ingredient a tofu extract having anti-inflammatory activity and osteoclast suppression effect.

According to the present invention, the worm extract of the present invention has anti-inflammatory activity and osteoclast inhibitory effect, and thus can be very useful in the functional food and pharmaceutical industry related to the development of preventive and therapeutic agents for rheumatoid arthritis patients.

In order to achieve the object of the present invention, the present invention provides a worm extract having anti-inflammatory activity and osteoclast inhibitory effect.

The osteoclast inhibition of the larvae extract of the present invention can be carried out by inhibiting the expression of Receptor Activator of NF-κB Ligand (RANKL).

In addition, the present invention provides a pharmaceutical composition for preventing or treating rheumatoid arthritis, containing the extract of the present invention as an active ingredient.

The larvae extract of the present invention is preferably extracted from the larva bark, more preferably from the hydrothermal extract of the larva bark, more preferably 550-650 g of the larva bark in 10,000-14,000 ml of water at 90-100 ℃ Hot water extraction for 2-4 hours, then concentrated in a vacuum concentrator at 40-50 ℃ until the solid content is 25-35%, and the concentrate can be obtained by lyophilization, most preferably 600 g of Peel bark It can be obtained by pouring into 12,000 ml, hot water extraction at 100 ° C. for 3 hours, and then concentrating at 45 ° C. until a solid content of 30% is obtained in a vacuum concentrator, and freezing-drying the concentrate.

The present invention also provides a health functional food for preventing or improving rheumatoid arthritis, which contains the worm extract as an active ingredient.

In the dietary supplement of the present invention, the larvae extract is preferably extracted from the bark of the larvae, more preferably from the hydrothermal extract of the larvae bark, more preferably 550-650 g of the larva bark in 10,000-14,000 ml of water Hot water extraction at 90-100 ° C. for 2-4 hours and then concentrating at 40-50 ° C. with a vacuum concentrator until 25-35% solids, the concentrate can be obtained by lyophilization, most preferably tofu 600 g of bark may be added to 12,000 ml of water, hot water extracted at 100 ° C. for 3 hours, and then concentrated at 45 ° C. until the solid content reaches 30%, and the concentrate may be obtained by lyophilization.

Hereinafter, the present invention will be described in more detail.

The worm extract of the present invention can be usefully used not only for rheumatoid arthritis, but also for stiffness of various inflammatory diseases and bone tissues.

The pharmaceutical composition for preventing or treating rheumatoid arthritis of the present invention may include 0.02 to 80% by weight of the extract, preferably 0.02 to 50% by weight, based on the total weight of the composition.

The pharmaceutical composition comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions.

The pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, and 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, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, 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 Various compounds or mixtures, including cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. 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 such solid preparations may include at least one excipient such as starch, calcium carbonate and 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 oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the extracts of the present invention vary depending 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 100 mg / kg, preferably 0.001 to 100 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 rats, mice, livestock, humans and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

In addition, the present invention provides a health functional food comprising the worm extract and food acceptable food supplements exhibiting an effect of preventing or improving rheumatoid arthritis. The larvae extract is preferably a hot water extract. Examples of the food to which the extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

It may also be added to foods or beverages for the purpose of preventing or improving diabetes. At this time, the amount of the extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml. have.

The health functional beverage composition of the present invention has no particular limitation on the other ingredients other than the above-mentioned extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract, for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. . The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

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 extracts of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components may be used independently or in combination, and the proportion of such additives is not so critical but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Example  1: Preparation of Tobacco Extract

600 g of Tobacco bark was added to 12,000 ml of water, extracted with hot water at 100 ° C. for 3 hours, and concentrated at 45 ° C. until the solid content reached 30%. The concentrate was lyophilized to obtain 150 g of powder.

Example  2: edema inhibitory effect of the worm extract of the present invention

The action of inhibiting carrageenan edema was investigated by the method of Winter et al. Edema was induced by subcutaneous injection of 0.1 ml of 1% carrageenan into the soles of 150-200 g male rats. Samples were orally administered 30 minutes before carrageenan injection. Measure the volume of edema four times at an interval of 1 hour after carrageenan injection, and then increase the rate based on the volume before injection (Winter, CA et al., Carrageenan-induced edema in hind). The degree of edema was calculated according to paw of the rat as an assay for anti-inflammatory drugs, Proc. Soc.Exp. Biol.Med., 111, 544 (1962)). Comparative experiment was performed by oral administration of the control drug ibulopene 200 mg / kg. The experimental results were calculated using the mean value and the standard error, and the comparison between each group was statistically significant when the P value was less than 5% using the Student's t-test.

As a result, the edema values showed a lower value than the control group to the worm extract extract, it was confirmed that the worm extract is effective in suppressing edema (Fig. 1).

Example  3: of the worm extract of the present invention Rheumatism  Arthritis Inhibitory Effect

In order to investigate the anti-inflammatory effect of rheumatoid arthritis on the extract of the worms, DBA / 1J mice (6 weeks old 25g, males (Central experimental animals)) were administered for 16 weeks. Arthritis was induced by dissolving collagen type 2 (Sigma, USA) in 0.1 M acetic acid at a concentration of 2 mg / ml and then emulsifying it in Freund's incomplete adjuvant (Sigma, USA). 100 μl was then injected subcutaneously into the right foot of the rat. Seven days after the first injection, the same amount was further inoculated in the tail portion and the control group was inoculated with the same amount of saline. Individuals forming periarticular redness, edema and swelling were visually selected on day 21 after the last inoculation. When the worm extract was administered, 200 mg / kg of the worm extract was dissolved in 0.9% physiological saline, filtered through a membrane filter (pore size 0.2㎛, Whatman), and orally administered once a day for 16 weeks.

As a result, the rheumatoid index showed a lower value than the control group of the worm extract extract, it can be seen that the worm extract extracts are effective in inhibiting rheumatoid arthritis (Fig. 2).

Example  4: arthritis knee joint of the present invention RANKL  Inhibitory effect

After 16 weeks, the mice of Example 3 were subjected to immunohistochemistry after blood was collected under ether anesthesia, and knee tissue was collected and demineralized.

Figure 3 is an inhibitory effect of RANKL of the larvae extract. Figure A shows the expression of RANKL in the arthritis knee joint as a control, Figure B shows that RANKL expression was suppressed in the arthritis knee joint group to the group of administration of the extract of the worms (Fig. 3).

1 is the edema inhibitory effect of the larvae extract.

Figure 2 is a rheumatoid index inhibitory effect of the worms extract.

Figure 3 is an inhibitory effect of RANKL of the larvae extract.

A: control group, B: toxin extract administration group.

Claims (10)

Tobacco extract with anti-inflammatory activity and osteoclast inhibitory effect. According to claim 1, wherein the osteoclast suppression is a worm extract, characterized in that by inhibiting the expression of receptor activator of NF-κB Ligand (RANKL). A pharmaceutical composition for preventing or treating rheumatoid arthritis, comprising the extract of the worms according to claim 1 or 2 as an active ingredient. The pharmaceutical composition for preventing or treating rheumatoid arthritis according to claim 3, wherein the larvae extract is a larvae bark extract. The pharmaceutical composition for preventing or treating rheumatoid arthritis according to claim 4, wherein the larvae extract is a hydrothermal extract of larvae bark. According to claim 5, The hydrothermal extract of the larva bark bark 550-650 g of the larva bark in 10,000-14,000 ml of water and hot water extracted for 2-4 hours at 90-100 ℃ and then the solid content at 40-50 ℃ with a vacuum concentrator A pharmaceutical composition for preventing or treating rheumatoid arthritis, which is concentrated to 25-35% and obtained by lyophilizing the concentrate. A functional health food for preventing or improving rheumatoid arthritis, comprising the extract of the worms according to claim 1 or 2 as an active ingredient. The method for preventing or improving rheumatoid arthritis according to claim 7, wherein the larvae extract is a larvae bark extract. The method for preventing or improving rheumatoid arthritis according to claim 8, wherein the larvae extract is a hydrothermal extract of the larvae bark. 10. The method of claim 9, wherein the hydrothermal extract of the larva bark is 550-650 g of the larva bark in 10,000-14,000 ml of water and hot water extracted for 2-4 hours at 90-100 ℃ and the solid content at 40-50 ℃ with a vacuum concentrator A functional health food for preventing or improving rheumatoid arthritis, which is obtained by concentrating until 25-35% and freezing-drying the concentrate.

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