KR20050097013A - The anti-inflammatory and anti-nociceptive effect of cinnamomum loureirii branches extract and pharmaceutical preparations containing the same - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the prevention and treatment of inflammatory diseases or arthritis containing the extract or fraction as an active ingredient, the extract and fraction of the present invention significantly inhibits the production of inflammation and edema and acute arthritis, osteoarthritis Because of its strong anti-inflammatory analgesic effect on rheumatoid arthritis, it can be used as an effective medicine and health functional food for general inflammatory diseases and arthritis.

Description

The anti-inflammatory and anti-nociceptive effect of Cinnamomum Loureirii branches extract and pharmaceutical preparations containing the same}

The present invention relates to a pharmaceutical composition for the treatment and prevention of inflammatory diseases or arthritis, containing the extract or fraction as an active ingredient.

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. (Miller MJ et al ., Mediators of inflammation , 4 , pp 387-396, 1995: Appleton L. et al ., Adv. Pharmacol. , 35 , pp 27-28, 1996).

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 frequent outbreaks are osteoarthritis (OA) and rheumatoid arthritis (RA). 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 cell regeneration, and its basic treatment is almost impossible. Surgical surgery, drug therapy, and physical therapy are being performed. There are many risks 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 cells play an important role along 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. This is accompanied by fever and physical 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, with many side effects such as 33% of patients at high doses have to stop taking it. 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, Chinese medicine and natural products, which have abundant clinical experience and excellent evaluation in terms of safety, are expected to be more developed as an arthritis treatment drug. Therefore, this study is to evaluate the anti-inflammatory and analgesic efficacy of herbal medicines that are used clinically in patients with arthritis and anti-inflammatory and anti- analgesic effect.

In Chinese medicine, arthritis is seen in the range of nasal congestion, and the etiology of the pathology is called “Wind-Han Samgi Magazine (風 寒濕 三 氣 雜 至), Hapseongbi” (合 而成 痺 也). A person who lacks) is believed to be caused by the invasion of external affairs and interfered with the communication of the meridians. Therefore, in the treatment, it removes the sarcasm and treats the dexterity. Myeongtang, Sipjeondaebotang, etc. are used, along with drug treatment of local acupuncture (치료) and physical therapy in combination. In oriental medicine, pain is mainly caused by impaired blood circulation by Hansa (sometimes caused by heat stroke), and accordingly, blood circulation is controlled as a method for controlling pain. Bedding or drugs have been used a lot.

Ginji (Cinnamomi Ramulus) of the present invention means that the branches of the broiler ( Cinnamomun loureirii NEES) cut to 15cm in length to dry in the sun, it is used as a herbal medicine. Taste is sour and gentle in nature. It emits abundant winds of the mark. Make it happen. The action of all over the body has the effect of active blood circulation and acidic pain, so it has an external feeling of cold (풍 感 痛), abundant humidity ratio (寒濕 痺) and menopause (經 閉), It is used to treat symptoms such as pain and pain. It also contains 0.07% alkaloids, 2.06% saponins, 2.51% tannins, and essential oils (Jung Bo-seop and Shin-Kyomin, Pharmacology, Yeonglimsa, p455,1998).

As a study on the cage, Korean Unexamined Patent Publication No. 2001-0055960 discloses a cosmetic composition containing a broiler extract, revealing an effect of inhibiting the enzymatic activity of elastase and hyaluronase of the broiler tree extract. 0095006 discloses broiler bark extracts having the same or similar control effects as chemicals.

However, no disclosure or teaching has been made of the therapeutic and prophylactic effects of gingival extracts on inflammatory diseases or arthritis.

Accordingly, the present inventors completed the present invention by revealing that the extract of the lanceolate is not only toxic, but also effective in preventing and treating acute arthritis without side effects during the various physiological activity studies of the lancet.

It is an object of the present invention to provide a pharmaceutical composition and health functional food for the prevention and treatment of inflammatory diseases including arthritis containing anti-inflammatory and analgesic activity extract.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of inflammatory diseases containing the extract or fraction as an active ingredient and a pharmaceutically acceptable carrier, excipient or diluent.

In another aspect, the present invention provides a pharmaceutical composition for the prevention and treatment of arthritis, containing the extract or fraction as an active ingredient and a pharmaceutically acceptable carrier, excipient or diluent.

The gage extract includes water and C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol and the like, and a mixture thereof, preferably an extract available in water or ethanol.

In addition, the fraction is soluble in water and polar solvents such as C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol and the like, nonpolar solvents such as hexane, ethyl acetate, acetone, chloroform, methylene chloride and mixed solvents thereof. One fraction, preferably fractions soluble in ethyl acetate, butanol and water.

The arthritis includes Osteoarthritis, psoriatic arthritis and Rheumatoid arthritis.

Hereinafter, the present invention will be described in detail.

Cage extract and solvent-specific fractions of the present invention can be obtained as follows.

The solvent of the present invention can be purchased by using a polar solvent of water and C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol, etc. in volume of about 2 to 15 times, preferably about 3 to 8 times the weight of the locking sample. Or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably hot water extraction, cold needle extraction, for about 1 hour to 1 day, preferably 1 hour to 4 hours at room temperature with water and ethanol, Using an extraction method such as reflux cooling extraction or ultrasonic extraction, preferably hot water extraction to recover the supernatant by vacuum filtration, and then repeat the above procedure 2 to 5 times, preferably 3 times Collected and concentrated under reduced pressure to obtain the water or ethanol extract.

In addition, water and organic solvents such as butanol, hexane, and ethyl acetate are added to the solvent ethanol extract obtained by the above process in order from low polarity solvent to high polarity solvent, preferably ethyl acetate, butanol and water. Fractionation and concentration under reduced pressure can be used to obtain fractions for each solvent, and additionally, conventional fractionation processes can be carried out (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis, 3rd Ed. , Pp 6-7, 1998 ).

The present invention provides a pharmaceutical composition for the prevention and treatment of arthritis, containing the extract and the solvent-specific fractions obtained by the above method as an active ingredient.

When oral administration of the gyeji extract of the present invention obtained by the above method to the rat and induce edema in the hind paws with carrageenan, it showed a significant edema inhibition rate compared to the control, and gyeji extract orally administered to the rat and Mycobacte In the case of inducing chronic arthritis in the hind paw with CFA (Freund's complete adjuvant) containing mycobacterium butyricium , it was confirmed that the anti-inflammatory effect was superior to the control group.

In addition, the gage of the present invention has been used as a herbal medicine for a long time, the extracts of the present invention extracted therefrom also have no problems such as toxicity and side effects.

The pharmaceutical composition for preventing and treating inflammatory diseases or arthritis of the present invention comprises 0.1 to 50% 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.

Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in any 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 , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable 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 at 0.001 to 100 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The extract of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

The present invention provides a health functional food comprising the extract and a food acceptable food supplement additive exhibiting a prophylactic effect of an inflammatory disease or arthritis. Examples of foods to which gage extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

It can also be added to foods or beverages for the purpose of preventing inflammatory diseases or 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 5g, preferably 0.3 to 1g based on 100ml. .

The health functional beverage composition of the present invention is not particularly limited to other ingredients except for having the extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates, etc. as additional ingredients, as in general 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 natural carbohydrates is generally about 1-20 g, preferably about 5-12 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.

Below, The invention is illustrated in detail by 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 Cinnamon Extract 1

Cinnamomi Ramulus was purchased (Gyeongdong Market), powdered with a crusher, 200g of the sample was placed in a 3 L flask, and 1,500 mL of distilled water was added thereto, followed by hot water extraction for 3 hours. This process was repeated three times, and the supernatant was collected, filtered through a filter paper, concentrated and dried under reduced pressure, to obtain 10.2 g (5.1%) of dried extract.

Example 2. Preparation of Cinnamon Extract 2

Ginji ( Cinnamomi Ramulus ) was purchased (Gyeongdong Market) and powdered with a crusher, 200g of the sample was placed in a 3L flask, and 1,500ml of 80% ethanol was added for 3 hours. This process was repeated three times, and the supernatant was collected, filtered through a filter paper, concentrated and dried under reduced pressure to obtain 7.0 g (3.5%) of dried ethanol extract.

Example 3 Preparation of Solvent Fractions by Solvent

5.5 g of the ethanol extract obtained in Example 2 was suspended in 1 L of water, and then solvent fractionation was performed sequentially from a solvent having a lower polarity to a solvent having a higher polarity in order of ethyl acetate, butanol and water, respectively. First, 1 liter of ethyl acetate was added to the ethanol extract suspended in 1 liter of water, and then dissolved. Then, only the components dissolved in the ethyl acetate layer were separated and dried under vacuum. This process was repeated three times to obtain an ethyl acetate fraction (0.7 g). 1 liter of butanol was added to the remaining aqueous layer, and only the components dissolved in the butanol layer were separated and dried in a vacuum. This process was repeated three times to obtain a butanol fraction (3.5 g), and finally, the remaining aqueous layer was concentrated under reduced pressure to obtain an aqueous layer fraction (1.3 g).

Experimental Example 1. Measurement of anti-inflammatory effect in carrageenan-induced acute arthritis model of rat

Using carrageenan induced arthritis (CIA) model, the effect of the extract and fractions of the above-mentioned Examples 1 to 3 on the acute arthritis was examined.

Sprague-Dawley's 180-200g rats (Samtaco Bio Korea, Korea) were used, and carrageenan (carrageenan, Sigma, USA) was used as a prophylactic agent for arthritis. 1% carrageenan solution was prepared by dissolving carrageenan type IV (lamda carrageenan, Sigma C3889) in physiological saline to 1%. Specifically, the concentration of the lyophilized extract and fractions of Examples 1 to 3 lyophilized 30 minutes before carrageenan was adjusted to 200, 500 and 1000 mg / kg, respectively, and then administered orally by 1 ml to the experimental group In addition, the control group was not administered the gage extract of the present invention. Inflammation was induced by subcutaneously injecting 50 μl per mouse into the hind paw of the mouse with the 1% carrageenan solution prepared above, followed by changes in edema every hour (1, 2, 3, 4, 5 hours). , Ugo Basil Co., Italy), and edema growth rate and edema inhibition rate were measured according to the following equations 1 and 2 and compared with the control group.

Edema increase rate (%) = [(foot edema before chlorine administration-foot edema after chlorine administration) / foot edema before chlorine administration] × 100

Edema inhibition rate (%) = [(average edema rate after a certain time of the control group-average edema rate after a certain time of the drug administration group) / average edema rate after a certain time of the control group] × 100

As a result, the acute model administered orally administered the extract and fraction of the present invention showed an excellent edema inhibitory effect compared to the control group did not administer the extract and fraction (see Table 1 and Table 2 below). Gyeji extract of the invention was confirmed that the acute anti-inflammatory effect.

Concentration-inhibitory Effect of Cage in Rat Carrageenan-induced Acute Arthritis Model group Dose (mg / kg) Change in foot volume (ml) 1 hr 2 hr 3 hr 4 hr 5 hr Control - 12.93 ± 4.50 86.82 ± 9.40 99.34 ± 7.35 116.76 ± 8.07 107.43 ± 7.38 80% Ethanol Extract 1,000 9.81 ± 6.03 (24.13) 39.15 ± 14.16 ^** (54.91) 60.11 ± 9.21 ^** (39.49) 76.31 ± 4.89 ^*** (34.64) 70.81 ± 4.67 ^** (34.09) 80% Ethanol Extract 500 16.41 ± 3.80 (<50) 40.63 ± 7.78 ^** (53.20) 69.98 ± 9.76 ^* (29.56) 77.73 ± 9.27 ^** (33.43) 78.64 ± 7.60 ^* (26.90) 80% Ethanol Extract 200 11.87 ± 4.00 (8.20) 50.84 ± 8.45 ^* (41.44) 68.31 ± 4.29 ^** (31.24) 80.21 ± 5.51 ^** (31.30) 78.19 ± 6.19 ^** (27.22) ^*** : p <0.001, ^** : p <0.01, ^* : p <0.05

Inhibitory Effect of Solvent Fraction from Sea Gage in Rat Carrageenan-induced Acute Arthritis Model group Dose (mg / kg) Change in foot volume (ml) 1 hr 2 hr 3 hr 4 hr 5 hr Control - 12.93 ± 4.50 86.82 ± 9.40 99.34 ± 7.35 116.76 ± 8.07 107.43 ± 7.38 80% Ethanol Extract 500 16.41 ± 3.80 40.63 ± 7.78 ^** (53.20) 69.98 ± 9.76 ^* (29.56) 77.73 ± 9.27 ^** (33.43) 78.64 ± 7.60 ^* (26.80) Ethyl acetate fraction 500 -3.03 ± 3.03 ^*** (> 90.0) -4.67 ± 4.20 ^*** (> 90.0) 11.91 ± 12.38 ^*** (88.01) 35.15 ± 25.23 ^** (69.901) 48.13 ± 22.43 ^* (55.20) Butanol fraction 500 1.41 ± 1.39 ^* (89.10) 32.29 ± 7.90 ^*** (62.81) 48.91 ± 9.39 ^*** (50.77) 78.91 ± 6.18 ^** (32.424) 91.72 ± 5.95 (14.62) Water fraction 500 8.57 ± 2.86 (33.72) 56.14 ± 10.55 ^* (35.34) 82.27 ± 11.08 (17.18) 93.15 ± 7.82 (20.22) 99.07 ± 8.97 (7.780) ^*** : p <0.001, ^** : p <0.01, ^* : p <0.05

Experimental Example 2. Measurement of anti-inflammatory analgesic effect in adjuvant-induced chronic arthritis model of rat

By using the Freund's complete adjuvant (CFA) -induced chronic arthritis model containing Mycobacterium butyricium (CFA) as a inflammatory agent in white paper, the extracts of Examples 1 to 3 were used for chronic anti-inflammatory pain. The impact was examined.

2-1. Induction of Chronic Arthritis

Inhalation anesthesia with 3% isoflurane using Sprague-Dawley male rats (Samtaco Bio Korea, Korea) of body weight 180-200 g, followed by 50 per ml in mineral oil. After mg suspension of CFA, chronic arthritis was induced by subcutaneous injection of 50 µl into the subcutaneous region of the right foot of the animal. The experimental animals injected with CFA were transferred to the laboratory, freely feeding and watering, and investigating the induction of arthritis and other disease states, and the experimental animals successfully induced arthritis were used in this experiment.

In general, acute inflammatory reactions are induced within several hours from the right foot injected with CFA, and arthritis with edema is induced in the opposite foot injected from 12 to 15 days after the injection.

2-2. Oral Administration of Cage Extracts

Drugs were administered orally to determine the anti-inflammatory analgesic effect of the arthritis extract of Chronic Arthritis of Examples 1 to 3. Specifically, the drug dose for one white rat was based on the weight of 200 g, and the control white rat was administered only 1 ml of 1% CMC aqueous solution and solid feed, and the experimental white rat was extract of per capita perilla (200 mg / kg). , 500 mg / kg) was administered orally daily.

The drug was administered in the same manner as described above. After inducing arthritis to find out the therapeutic and prophylactic effect, the animals were fed with solid feed under the same conditions for 3 weeks and confirmed the change in arthritis. The drug was administered for 3 weeks. Three weeks after drug administration, 10 experimental groups and 10 control groups were sampled.

2-3. Measurement of edema

Chronic arthritis is induced by Experimental Example 2-1, and the degree of edema is measured by an edometer (Ugo Basil Co., Ltd.) in order to measure the anti-inflammatory effect in animal joints administered orally by the same method as Experimental Example 2-2. Italy), ankle edema was measured every 3 days after induction and compared with the control. In addition, by measuring the edema growth rate (%) and edema inhibition rate (%) according to the equations (1) and (2) to observe the degree of reduction of edema according to the anti-inflammatory effect of the extract of the present invention.

As a result of the experiment, the addition of the gyeji extract of the present invention, ankle edema was significantly reduced compared to the control group did not add the gyeji extract, it is effectively reduced in the left foot than in the right foot, there is an anti-inflammatory analgesic effect in osteoarthritis In addition, it was confirmed that the anti-inflammatory analgesic effect is excellent even in rheumatoid arthritis (see Table 3 and Table 4 below).

Anti-inflammatory Effect on Right Foot Edema in Rats Using Immunoresponder-induced Chronic Arthritis Hours Change in right foot volume (ml) No treatment group Control Cinnamon Extract (200mg / kg) Cinnamon extract (500 mg / kg) 3 1.96 ± 0.07 1.87 ± 0.05 6 1.97 ± 0.08 2.06 ± 0.89 12 2.44 ± 0.06 ^* 2.58 ± 0.06 2.45 ± 0.07 (44.83) 2.38 ± 0.05 ^* (68.97) 15 2.89 ± 0.09 2.99 ± 0.10 2.60 ± 0.05 ^** (73.58) 2.71 ± 0.07 ^* (52.38) 19 2.89 ± 0.09 2.66 ± 0.09 2.70 ± 0.13 2.67 ± 0.13 21 2.81 ± 0.09 2.53 ± 0.08 2.70 ± 0.09 2.57 ± 0.06 ^*** : p <0.001, ^** : p <0.01, ^* : p <0.05

Effect of Chronic Anti-inflammatory on Left Foot Edema in Rats Using Immunopotentiator-induced Chronic Arthritis Model Hours (days) Edema volume (ml) No treatment group Control Cinnamon Extract (200mg / kg) Cinnamon extract (500 mg / kg) 12 0.48 ± 0.10 ^* 0.72 ± 0.07 0.56 ± 0.12 (66.77) 0.50 ± 0.08 (91.61) 15 0.93 ± 0.08 1.03 ± 0.04 0.71 ± 0.05 ^* (84.21) 0.82 ± 0.08 (55.26) 19 0.93 ± 0.10 0.80 ± 0.07 0.80 ± 0.15 0.78 ± 0.12 21 0.85 ± 0.12 0.66 ± 0.08 0.81 ± 0.10 0.67 ± 0.09 ^*** : p <0.001, ^** : p <0.01, ^* : p <0.05

2-4. Measurement of ankle circumference

Chronic arthritis is induced by Experimental Example 2-1, and the degree of inflammation is measured by measuring the ankle circumference to determine the anti-inflammatory effect in the animal joints administered orally by the same method as Experimental Example 2-2. The degree of inflammation reduction according to the anti-inflammatory effect of the extract was measured.

As a result of the experiment, when the extract was added, the left ankle edema was reduced compared to the control group without adding the extract, and it was confirmed that the left foot showed an anti-inflammatory effect in rheumatoid arthritis (Table 5 and Tables below). 6).

Anti-inflammatory Effect on Right Ankle Circumference in Rats Using Immunoresponder-induced Chronic Arthritis Model Hours (days) Right ankle circumference (cm) No treatment group Control Cinnamon Extract (200mg / kg) Cinnamon extract (500 mg / kg) 9 2.56 ± 0.02 ^*** 3.04 ± 0.02 2.93 ± 0.03 ^** 2.89 ± 0.06 ^* 12 2.46 ± 0.02 ^*** 2.83 ± 0.03 2.86 ± 0.03 2.84 ± 0.04 15 2.51 ± 0.03 ^*** 2.83 ± 0.02 2.85 ± 0.03 2.83 ± 0.04 18 2.44 ± 0.02 ^*** 2.82 ± 0.03 2.84 ± 0.03 2.85 ± 0.05 21 2.46 ± 0.02 ^*** 2.87 ± 0.04 2.94 ± 0.05 2.91 ± 0.06 ^*** : p <0.001, ^** : p <0.01, ^* : p <0.05

Anti-inflammatory Effects on Left Ankle Circumference in Rats Using Immunoresponder-induced Chronic Arthritis Model Hours (days) Left ankle circumference (cm) No treatment group Control Cinnamon Extract (200mg / kg) Cinnamon extract (500 mg / kg) 9 2.57 ± 0.02 2.44 ± 0.03 2.47 ± 0.05 2.45 ± 0.03 12 2.47 ± 0.03 2.44 ± 0.02 2.41 ± 0.05 (0.552) 2.50 ± 0.02 15 2.49 ± 0.03 2.39 ± 0.02 2.48 ± 0.02 2.45 ± 0.02 18 2.44 ± 0.02 2.40 ± 0.02 2.45 ± 0.02 2.42 ± 0.03 21 2.47 ± 0.02 2.39 ± 0.01 2.48 ± 0.03 2.48 ± 0.02 ^*** : p <0.001, ^** : p <0.01, ^* : p <0.05

Experimental Example 3. Anti-inflammatory Effect Using Mouse Macrophages

In order to measure the anti-inflammatory effect on inflammatory cells, the extracts and fractions obtained in Examples 1 to 3 by measuring the degree of inhibiting the production of LPS (lipopolysaccharide) induced NO (Nitric Oxide) in mouse macrophage Raw 264.7 cells The anti-inflammatory effect of was measured.

That is, RAW264.7 cells were adjusted to 1.0x10 ⁶ cells / ml using DMEM medium, and then inoculated into 96 well plates, and the cells were stabilized by pre-cultivation for 4 hours, followed by test material and LPS (1 µg / ml). Fresh media containing were simultaneously treated and incubated for 24 hours. The amount of generated NO was measured in the form of NO ₂ ⁻ present in the cell culture liquid using a grease reagent. Mix 100 μl of cell culture supernatant with 100 μl of grease reagent (1% (w / v) sulfanilamide, 0.1% (w / v) napthylethylenediamine in 2.5% (v / v) phosphoric acid) for 10 minutes in a 96-well plate After the absorbance was measured at 540 nm. 540 nm was measured using an ELISA reader, and sodium nitrite (NaNO ₂ ) was compared as a standard.

As a result, the NO production was significantly inhibited in 100, 50 and 20 µg / ml of the 80% ethanol extract of Example 2, and significant NO in the ethyl acetate fraction 50, 20 and 10 µg / ml of Example 3, respectively. It showed production inhibitory activity (p = 0.001). From these results, it was confirmed that the anti-inflammatory effect by inhibiting the NO production of LPS-induced inflammatory response in macrophages (see Figure 3).

Experimental Example 4. Acute Toxicity Test

Acute toxicity test was performed using 6-week-old specific pathogen-free (SPF) SD rats. Two animals of each group were administered orally once with the dose of 100 mg / kg of the extract of the present invention. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed. Hematological and hematological examinations were performed. Necropsy was performed to visually observe abnormalities in organs and thoracic organs.

As a result, no significant clinical symptoms or dead animals were noted in all animals treated with the test substance, and no toxic changes were observed in weight changes, blood tests, blood biochemical tests, and autopsy findings. As a result, the ginseng extract of the present invention did not show a toxic change even in rats up to 100 mg / kg, respectively, and the minimum lethal dose (LD ₅₀ ) was determined to be a safe substance of 100 mg / kg or more.

One example of the formulation of the pharmaceutical composition comprising the extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail.

Formulation Example 1 Preparation of Powder

Cage Extract Powder 20 mg

Lactose 100 mg

Talc 10 mg

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

Formulation Example 2 Preparation of Tablet

Cage Extract Powder 10 mg

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.

Formulation Example 3 Preparation of Capsule

Gage fraction powder 10 mg

3 mg of crystalline cellulose

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.

Formulation Example 4 Preparation of Injection

Cage Extract Powder 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _{4 12} H 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).

Formulation Example 5 Preparation of Liquid

Cage Extract Powder 20 mg

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.

Formulation Example 6 Preparation of Healthy Food

Cinnamon Extract Powder 1000mg

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

Folate 50 ㎍

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, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation Example 7 Preparation of Healthy Drink

Keji fraction powder 100 mg

15 g of vitamin C

100 g of vitamin E (powder)

Iron lactate 19.75 g

3.5 g of zinc oxide

Nicotinamide 3.5 g

0.2 g of vitamin A

0.25 g of vitamin B ₁

0.3 g of vitamin B ₂

Water quantification

After mixing the above components in accordance with a conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

As described above, the extract and fractions of the present invention significantly inhibits inflammation and edema production and exhibits strong anti-inflammatory analgesic effect in acute arthritis, osteoarthritis and rheumatoid arthritis, and thus are effective for general inflammatory diseases and arthritis. It can be used as a functional food.

1 is a diagram showing the degree of reduction of edema upon oral administration of an acute arthritis animal model induced by carrageenan at various concentrations of the ethanol extract of the present invention,

Figure 2 is a diagram showing the degree of edema is reduced when orally administered to the carrageenan-induced acute arthritis animal model of the basal fraction of the present invention,

Figure 3 is a diagram showing the degree of inhibition of NO production produced when administered ethanol extract and fractions of the present invention to mouse macrophages.

Claims (8)

A pharmaceutical composition for the prevention and treatment of inflammatory diseases, comprising the extract or fraction as an active ingredient and comprising a pharmaceutically acceptable carrier, excipient or diluent. A pharmaceutical composition for the prevention and treatment of arthritis, which comprises the extract or fraction as an active ingredient and comprises a pharmaceutically acceptable carrier, excipient or diluent. The pharmaceutical composition according to claim 2, wherein the arthritis is at least one selected from the group consisting of osteoarthritis, psoriatic arthritis, and rheumatoid arthritis. The pharmaceutical composition according to claim 1 or 2, wherein the sessile extract is water and an extract available for C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol and the like, or a mixed solvent thereof. The method according to claim 1 or 2, wherein the locking fraction is water and a polar solvent such as C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol and the like, non-polar such as hexane, ethyl acetate, acetone, chloroform, methylene chloride, etc. A pharmaceutical composition which is a fraction soluble in a solvent or a mixed solvent thereof. 6. The pharmaceutical composition according to claim 5, wherein the locking fraction is a fraction soluble in ethyl acetate, butanol or water. A dietary supplement comprising cinnamon extract, fractions and food acceptable food supplements that have an effect of preventing and improving inflammatory diseases or arthritis. The health functional food according to claim 7, which is a health beverage.