KR20120073797A - Pharmaceutical composition comprising for preventing and treating an articular rheumatism, extract from the mixture of ponciri fructus, lonicerae flos and angelicae dahuricae radix - Google Patents

Abstract

The present invention relates to a herbicidal, gold and silver herb mixture extract having an anti-inflammatory effect and a pharmaceutical composition containing the same. Specifically, since the composition of the present invention has an anti-inflammatory and pain inhibitory effect, the composition comprising the same is rheumatoid It can be usefully used as an effective medicine and health functional food for the prevention and treatment of sexual arthritis.

Description

Pharmaceutical composition comprising for preventing and treating an articular rheumatism, extract from the mixture of Ponciri Fructus, Lonicerae Flos and Angelicae Dahuricae Radix}

The present invention relates to a pharmaceutical composition for the prevention and treatment of rheumatoid arthritis, which contains as an active ingredient a herbal extract of fruit, gold, silver and white paper having anti-inflammatory and pain inhibitory effects.

Inflammation is the expression of in vivo defense mechanisms against various forms of infection or stimulants in metabolites in vivo, and various chemical mediators are involved in the mechanism of inflammation. Complex. Existing anti-inflammatory drugs are classified into steroidal and non-steroidal anti-inflammatory drugs. Most of the synthetic anti-inflammatory drugs have various side effects in addition to the main action, so the effects are excellent and the development of anti-inflammatory drugs with fewer side effects is urgently required. It is true.

Arthritis is a disease characterized by symptoms such as swelling and redness in which softening and pain last for more than two weeks. Arthritis can be classified into at least 100 forms, but the most common causes are osteoarthritis and rheumatoid arthritis. Osteoarthritis, also called degenerative arthritis, is caused by the destruction of the cartilage that surrounds the bones due to ageing of the joints, causing severe pain and joint stiffness, and in most cases called 'spurs'. The protrusions on the bone grow, making the pain even worse. Osteoarthritis, in particular, is a degenerative disease that occurs in older people with reduced metabolism and cellular regeneration, and its fundamental treatment is almost impossible. Surgical surgery, drug therapy, and physical therapy are being performed, but except for some adjuvant therapy Take the risk of side effects. Rheumatoid arthritis is a disease that causes chronic non-bacterial inflammatory reactions in the synovial membrane of the joints or tendons (tendons), causing the synovial membrane to proliferate and the amount of synovial fluid to increase, leading to swelling and pain in the joints. Rheumatoid arthritis is a systemic inflammatory reaction that affects many tissues and organs (skin, blood vessels, heart lungs, muscles) in the human body, especially the joints, which causes irreversible proliferative synovitis, which leads to the destruction of articular cartilage and Proceeds to rigidity. The cause of rheumatoid arthritis is not known yet, but autoimmune reactions are known to play an important role in the chronic and progression of the disease. In other words, T cell plays an important role with local release of inflammatory mediators and cytokines, resulting in a sustained autoimmune reaction that destroys joints. The main symptoms are fatigue, weakness, and pain. As it progresses, it is accompanied by fever and weakness. In addition, muscle atrophy and muscle spasm appear near the inflamed joint, affecting joint movement.

In modern times, arthritis is a general disease that has become low and widespread due to the rapid increase in obesity patients due to changes in eating habits and the development of traffic, but there is no selective treatment drug since the mechanism of arthritis is not known yet. Therefore, the purpose of the treatment of arthritis is to reduce the pain and inflammation of the joint, and to prevent the deformation of the joint. Since there is no fundamental treatment for arthritis, basic therapy is physical and exercise therapy, and moderate nonsteroidal anti-inflammatory drugs (NSAIDs) are used to relieve inflammation, and if inflammation is severe, gold salt therapy or penicillamine ) Therapy is performed. If the above method is ineffective, a steroid (steroid) agent is used, and if refractory is used, an immunosuppressant is used, and when transitioned to osteoarthritis, surgery is performed. Non-steroidal anti-inflammatory drugs (NSAIDs), which are used for anti-inflammatory and analgesic effects on arthritis, mainly inhibit cyclooxygenase and inhibit the production of prostaglandin, which is involved in inflammatory reactions. Among them, indomethacin and phenylbutazone have stronger anti-inflammatory effects than other NSAIDs. Indomethacin is one of the most potent drugs that inhibit the production of prostaglandins that cause inflammation, and is well absorbed by oral administration.In addition to the common gastrointestinal side effects seen in NSAIDs, indomethacin is associated with dizziness, delirium, and rarely hallucinations. Psychosis is severe enough to be reported and has many side effects, such as 33% of patients at high doses have to stop taking the drug. Phenylbutazone has also been used to treat rheumatoid arthritis, ankylosing spondylitis, and acute gouty arthritis in comparison to other NSAIDs in the early stages of use, but is not currently used due to severe toxicity including hematologic abnormalities causing granulocytopenia or aplastic anemia. Compared to these NSAIDs, steroid preparations are the fastest methods available to patients, and are known to have fast and dramatic anti-inflammatory effects and delight patients. However, as is widely known, the drug weakens resistance to bacterial infections, causes diabetes to worse, Cushing's syndrome, adrenal insufficiency, and mental dysfunction. It is known to be difficult to use because it is difficult and should be prohibited if possible. As described above, since synthetic anti-inflammatory drugs often have various side effects, the development of anti-inflammatory drugs having strong effects and relatively low side effects as described above are constantly required. In particular, in terms of efficacy and side effects, herbal medicines and natural products, which have abundant clinical experience and excellent evaluation in terms of safety, are considered to be more likely to be developed as arthritis therapeutic drugs. Therefore, this study was conducted to evaluate the anti-inflammatory and analgesic efficacy of herbal combinations, which are used clinically in patients with arthritis and anti-inflammatory and anti-pain (= analgesic) effects. .

As used in the present invention, Ponciri Fructus is a dried fruit of the Pancirius trifoliata, and is mostly hemispherical, and its outer surface is dark green to brown, with many rough and concave small dots. . The epidermis of the cross section is yellowish brown and the inside is light grayish brown, and the center consists of 8 to 16 small rooms radially. Each room is dry, yellowish brown, concave and sometimes contains less ripe seeds. It has a peculiar smell and taste, and is used in fragrant high-density placebo (Medicine Index, Korea Medical Index, p604, 1988).

Lonicerae Flos is also called as a fairy tale, silver or pear, and belongs to the family of aphidae, known as Lunicera japonia Thunberg. Gold and silver has long been widely used in folk remedies and herbal detoxification medicines, and its extracts and some active ingredients have various pharmacological effects such as anti-influenza virus, antibacterial, antifungal, anti-inflammatory and antipyretic effects. It is widely applied to the treatment of various diseases (Korean Research Institute of Useful Plant Resources, Korea Research Institute of Chemical Technology, pp 201-204 (1988): Oriental Medicine Clinical Application, Seongbosa, pp140-142, 1982).

The white paper (Angelicae Dahuricae Radix) is usually fusiform with many long roots splitting from short roots, 10-25cm long, grayish brown to dark brown on the outside. Some leaves remain on the head and narrowly marked spines. Roots have vertical wrinkles and several fine root marks. The perimeter of the cross section is grayish white with many gaps, and the center is dark brown. It has a peculiar smell and slightly bitter taste, and the result of pharmacological experiments has sedation, jingyeong, and antibacterial effects (Herbal Medical Standards, Korea Medical Index, p520, 1988).

Oriental medicine has described the symptoms of arthritis in the modern sense through the concept of pathology called asymptomatic. In addition, various complex herbal prescriptions and single herbal medicines, which can control the disease, have been recorded in many traditional oriental medicine books. Therefore, the present inventors have developed a herbal medicine complex, which is an herbal extract of fruit, gold, silver and white paper, which has no Western medical side effects, through the anti-inflammatory and analgesic effects of dozens of herbal medicines that have been used empirically to control such nausea in this study. By pharmacologically observing the anti-inflammatory and analgesic effects, it was confirmed that the effect of preventing and treating rheumatoid arthritis was excellent, and completed the present invention.

An object of the present invention relates to a composition effective in the prevention and treatment of rheumatoid arthritis, which contains as an active ingredient herbal extract of fruit, gold, silver and white paper having anti-inflammatory and analgesic effect.

In accordance with the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of rheumatoid arthritis, which contains a mixed herbal extract of fruit, gold, silver and white paper as an active ingredient.

The herbal mixed extract of the fruit, gold, silver and white paper includes extracts soluble in water.

Hereinafter, the present invention will be described in detail.

The herbal mixed extracts of the fruiting, sterling and white paper of the present invention can be obtained as follows.

After extracting or purchasing the herbal mixed extracts of the fruiting, gold, silver and white paper of the present invention, dried and powdered with a crusher, about 2 to 20 times the dry weight of the herbal mixed extract of the fruit, gold, silver and white paper, preferably about 8 Hydrothermal extraction, cold extraction, reflux cooling extraction or ultrasonic extraction with a volume of water up to 15 times at 70-100 ° C., preferably at 100 ° C. for about 1 minute to 12 hours, preferably 15 minutes to 3 hours. After extracting using the method of hot water extraction, the extract was allowed to cool at room temperature, and then the supernatant was recovered by filtration, and the above procedure was repeated 2 to 5 times, preferably 3 times, to collect the supernatant and depressurize. After concentration, lyophilization can be used to obtain a mixed herbal extract of fruit, gold and white paper of the present invention. Although the mixing amount of the fruit, gold and silver paper of the present invention is not particularly limited, it is effective to extract the mixture by the same content.

The present invention provides a pharmaceutical composition for the prevention and treatment of rheumatoid arthritis, which contains the mixed extract of the herbaceous fruit, gold, silver and white paper obtained by the above method as an active ingredient.

In addition, the herbal extracts of the fruit, gold, silver and white paper is a drug that has been used as a herbal medicine for a long time, the extract of the present invention extracted therefrom also has no problems such as toxicity and side effects.

As a result of searching the anti-inflammatory and analgesic effect of the herbal extracts of the fruit, gold, silver and white paper obtained by the above method, it was confirmed that the prevention and treatment of rheumatoid arthritis.

The pharmaceutical composition for preventing and treating rheumatoid arthritis of the present invention comprises 0.1 to 80% by weight of the extract based on the total weight of the composition.

Pharmaceutical compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture 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. Examples of carriers, excipients and diluents that can be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, 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 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 100mg / kg, preferably 0.001 to 10mg / kg per day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

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 can be expected, for example by oral, rectal or intravenous, arterial, intraosseous, intramuscular, subcutaneous, intrauterine, dural or cerebrovascular (intracerebroventricular) injections.

The present invention provides a dietary supplement for the prevention and treatment of rheumatoid arthritis, comprising the extract and a food supplement acceptable food supplement.

Examples of the food to which the extract of the present invention can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

It may also be added to food or beverages for the purpose of preventing and treating rheumatoid arthritis. 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 1g 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. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate 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 can be used independently or in combination. The proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

As described above, the herbal mixed extract of the fruit fruit, gold, silver and white paper of the present invention exhibits excellent anti-inflammatory and pain inhibitory effect in the anti-inflammatory and analgesic effect experiments, and thus, the composition comprising the herbal extract of fruit, gold, silver and white paper May be usefully used as a medicine and health functional food for preventing and treating rheumatoid arthritis.

Hereinafter, the present invention will be described in detail with reference to the following examples and experimental examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Example 1 Preparation of a Herbal Medicine Mixture Extract of Fruits, Geummi and White Paper

In order to manufacture herbal extracts of Jisil, Geumeun Hwa and White Paper, Jisil, Geumeunhwa and White Paper (Gyeongdong Market, Seoul, South Korea) purchased from Gyeongdong Herbal Medicine Market were selected and sliced. (100 g: 100 g: 100 g) was mixed in the same amount, 3 L of deionized secondary distilled water was added, and extracted with hot water for two hours at 100 ° C. The extract was left to cool at room temperature, filtered through a filter paper (Whatman, USA), and then concentrated under reduced pressure with a vacuum condenser (EYELA, N-1000, Japan) and lyophilized to extract a mixture of herbal extracts of fruit, gold, silver and white paper ( Hereinafter referred to as JGB).

Example 2 Anti-inflammatory Effect Measurement

The anti-inflammatory effect was verified according to the method described in the literature (Winter, CA, Riskey et al., Proc. Soc. Exp. Med. 111, p544, 1962), and 6 male SD rats weighing about 200 g were weighed. As a group 1, JGB and other drugs were orally administered, and 1 hour later, 1% carrageenin solution as an inflammation-causing substance was injected subcutaneously into the center of the right rear foot. The volume of foot edema occurring 3 hours after carrageenan injection was measured using a plethysmometer and the anti-inflammatory effect of LK758 was verified by calculating the edema inhibition rate. As a positive control drug, aspirin 200 mg / kg, which is a representative nonsteroidal anti-inflammatory drug, and 400 mg / kg of SKI306X (trade name: JOINS), which is already used for the treatment of chronic rheumatoid arthritis, were used.

As a result, the JGB 100mg / kg, 250mg / kg and 500mg / kg groups showed edema inhibition rates of 8%, 14% and 29% after 3 hours of carrageenan injection, respectively, and were treated with aspirin 200mg / kg and SKI306X 400mg. The / kg group showed inhibition rates of 48% and 30%, respectively. As a result, JGB showed a weaker anti-inflammatory effect at 500 mg / kg dose than the synthetic drug aspirin, but it had a similar anti-inflammatory effect to SKI306X, a conventional herbal compound.

Example 3 Analyzing Analgesic Effect

Analyzes of analgesic effects were performed according to the method described in Koster, R. et al., Fed. Proc., 412, p18, 1985. 10 ICR male mice weighing 25g were treated as a group, and a dose of JGB and other drugs was orally administered, and 1 hour later, 0.6% acetic acid diluted with physiological saline was intraperitoneally injected at a dose of 0.1ml per 10g body weight of the mouse. It was. 10 minutes after the injection, the number of occurrences of specific writhing reactions of each mouse was measured, and the analgesic effect by JGB was verified by comparing between the control group and no drug group. As a positive control drug, aspirin 200 mg / kg, which is a representative nonsteroidal anti-inflammatory drug, and 400 mg / kg of SKI306X (trade name: JOINS), which is being used for the treatment of chronic rheumatoid arthritis, were used.

As a result, the JGB 100mg / kg, 250mg / kg and 500mg / kg administration group showed pain inhibition rate of 18%, 40% and 76%, respectively, based on the control group. Aspirin 200mg / kg group showed a 38% pain inhibition, and SKI306X 400mg / kg group showed a 74% pain inhibition. As a result, JGB has a superior analgesic effect than the synthetic drug aspirin at the dose of 500mg / kg, and shows an analgesic effect similar to that of SKI306X, a conventional herbal compound.

Example 4 Toxicity Test

In order to test the toxicity of the herbal mixed extract of the fruit, gold and silver paper of the present invention, animal experiments were conducted.

25 ± 5g of ICR mice (central laboratory animals) and 235 ± 10g of SPF Sprague Dawley (Biogenomics) rats were divided into three groups of 3 rats, respectively, obtained in Example 1 above. Toxicity was observed for 14 days after intraperitoneal administration of herbal extracts of one fruit, gold and white paper at doses of 1000 mg / kg, 500 mg / kg and 100 mg / kg, respectively.

As a result, no deaths were observed in all three groups, and no significant symptoms were found in weight gain and feed intake. Therefore, it could be confirmed that the herbal extract of the fruit of the present invention, gold, silver and white paper is a safe substance.

The pharmaceutical composition comprising the herbal extract of the fruit, gold, silver and white paper of the present invention may be administered in the following formulations, and the following formulation examples are merely illustrative of the present invention, whereby the content of the present invention is limited. no.

[Preparation Example 1] Preparation of powder

20 mg of extract of Example 1

Lactose 100 mg

Talc 10 mg

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

Preparation Example 2 Preparation of Tablet

10 mg of extract of Example 1

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Production Example 3 Preparation of Capsule

10 mg of extract of Example 1

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

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

Production Example 4 Preparation of Injection

10 mg of extract of Example 1

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na2HPO ₄ , 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Production Example 5 Preparation of Liquid

20 mg of extract of Example 1

10 g of isomerized sugar

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding lemon flavor appropriately, mixing the above components, adding purified water, adjusting the whole to 100 ml by adding purified water, and then filling into a brown bottle. The solution is prepared by sterilization.

Production Example 6 Production of Health Food

1000 mg of extract of Example 1

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Production Example 7 Preparation of Healthy Drinks

1000 mg of extract of Example 1

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (8)

(a) hot water extraction after mixing the citric, gold and white paper; And
(b) filtering the extract from step (a) and then lyophilizing by concentrating under reduced pressure; Herbal mixture extract manufacturing method comprising a.
The method of claim 1,
The extract of hot water of step (a) is a method for producing a herbal mixture extract is carried out at 70 to 100 ℃.
Herbal mixture extract prepared according to the method of claim 1 or 2.
A pharmaceutical composition for preventing and treating rheumatoid arthritis, comprising the herbal extract of claim 3.
The method of claim 4, wherein
The pharmaceutical composition is a pharmaceutical composition as an oral dosage form in the form of a powder, granules, tablets, capsules, suspensions, emulsions, syrups or aerosols.
The method of claim 4, wherein
The pharmaceutical composition is a pharmaceutical composition in the form of external preparations, suppositories or sterile injectable solutions.
Claim 3, health functional foods for preventing and improving rheumatoid arthritis, including the herbaceous mixture of gold, silver and white paper and food supplements.
8. The method of claim 7,
The health functional food is a health functional food.