KR100656571B1 - Composition for preventation and treatment of degenerative arthritis - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of degenerative arthritis, specifically, Uji extract mixture (30% by weight of glucosamine, 69% by weight of Uji extract and 1% by weight of silicon dioxide) 80 to 90 parts by weight, shark cartilage extract 2 to 8 By weight, characterized in that it comprises 2 to 8 parts by weight of Hagocho extract and 2 to 8 parts by weight of St. John's wort extract.

The composition of the present invention significantly inhibits the activity of hyaluronidase and significantly reduces pain, and thus can be used as a medicine and health food useful for the prevention and treatment of degenerative arthritis.

Description

Composition for preventation and treatment of degenerative arthritis             

1 is a diagram showing the effect of the extract mixture of the present invention on chondrocyte collagen type II expression.

The present invention relates to a composition for the prevention and treatment of degenerative arthritis, specifically, Uji extract mixture (30% by weight of glucosamine, 69% by weight of Uji extract and 1% by weight of silicon dioxide) 80 to 90 parts by weight, shark cartilage extract 2 to 8 By weight, characterized in that it comprises 2 to 8 parts by weight of Hagocho extract and 2 to 8 parts by weight of St. John's wort extract.

Degenerative arthritis is a disease in which local degenerative changes occur as the articular cartilage wears off. Also called osteoarthritis or osteoarthritis. Osteoarthritis is a representative degenerative disease that is closely related to aging. About 10 to 15% of the entire population suffers from osteoarthritis. In particular, about 60 to 80% of the elderly aged 65 or older suffer from osteoarthritis.

The causes of degenerative arthritis are deeply related to aging and excessive weight, and the more and more severely in women as they age. Early symptoms include one or two joints with stiff pain, such as stiffness, and prolonged prolongation of the cartilage, hardening of the subchondral bone, excess bone formation around the joint, and deformation of the joint.

Degenerative arthritis can be classified as primary (primary) or secondary (secondary).

First, the primary cause of primary degenerative arthritis is not known, but age, sex, genetic factors, and obesity are thought to be the cause. Primary (primary) degenerative arthritis is more common in women after middle age and more frequently in women. It is also related to family history. In the case of obesity, the incidence is about 2 times higher than that of a normal person, and it is mainly shown in a weight bearing joint. Commonly involved joints include weight-bearing and compression of the lumbar spine, hips, knees, and metatarsal joints of the foot's moss. In particular, even within the joint, a certain area, ie, the inner joint of the knee joint, is well invaded. In females, the distal joints of the resin (finger joints away from the torso) and the first carotid metacarpal joints (palm of the palm of the hand) are well invaded, and in men, hip involvement is common.

Second, secondary (secondary) degenerative arthritis can be caused by trauma, disease and malformations that can damage joint cartilage. Congenital malformations include a lack of joint alignment, such as hip dysplasia or varus, and joint cartilage destruction after purulent / tuberculous arthritis is often associated with acute necrosis, severe shock, or repeated trauma. . In addition, many degenerative arthritis also occur in endocrine abnormalities such as acromegaly and diabetes, and metabolic diseases such as gout.

The cause of degenerative changes in articular cartilage has not yet been identified, but an absolute decrease in the number of chondrocytes and imbalances in the synthesis and degradation of chondrocytes in chondrocytes is known as one cause. Thus, degenerative changes in articular cartilage reduce cartilage strength and ability as a cushion due to degradation of cartilage substrate.

Hyaluronic acid (hyaluronic acid) is a substance that is contained in cartilage tissue in vivo, it plays a big role in increasing the elasticity of the cartilage tissue, has a high moisture content, and has excellent viscoelasticity. In general, acceleration of hyaluronic acid is observed in osteoarthritis patients. In addition, there is a research report that collagenase and hyaluronidase increase the cell death of articular chondrocytes and decrease the metabolism of chondrocytes, thereby promoting the degenerative changes of chondrocytes. Therefore, it is thought that the inhibition of hyaluronidase, a hyaluronic acid degrading enzyme, may have a therapeutic effect of osteoarthritis.

Treatment of degenerative arthritis that is currently used clinically includes drug treatments (painkillers, steroids, nonsteroidal anti-inflammatory drugs, etc.) or cartilage protective agents (hyaluronic acid, glucosamine, chondroitin, etc.) or surgical treatment (arthroscopic surgery, Proximal tibia osteotomy, joint replacement, total knee arthroplasty, etc.). However, drug therapy has only the effect of non-specifically relieving pain or inflammatory response itself, and cartilage protection agent only serves to protect joints by nourishing chondrocytes or alleviating shock. In addition, there is a side effect that can lead to osteoporosis, hypertension, diabetes, etc. due to loss of calcium when taking steroidal drugs for a long time. Therefore, in most cases, the drug is used only for the purpose of reducing pain, and permanent arthroplasty is mainly used, but there are no drugs or surgical methods that provide a fundamental therapeutic effect.

Accordingly, the present inventors are searching for an alternative to minimize the side effects of the existing arthritis therapeutic agent and reduce the pain of arthritis as much as possible, while the mixture of Uji extract mixture, shark cartilage extract, hachicho extract and St. John's wort extract is hyaluronides The present invention was completed by remarkably inhibiting the activity of and reducing the pain.

The present invention is to provide a composition for the prevention and treatment of degenerative arthritis, including a Uji extract mixture (glucosamine, Uji extract and silicon dioxide), shark cartilage extract, hyacinth extract and St. John's wort extract.

The present invention provides a composition for the prevention and treatment of degenerative arthritis, including a Uji extract mixture (glucosamine, Uji extract and silicon dioxide), shark cartilage extract, hyacinth extract and St. John's wort extract.

Compositions of the present invention include pharmaceuticals and health foods useful for the prevention and treatment of degenerative arthritis.

Hereinafter, the present invention will be described in detail.

The composition of the present invention comprises 80 to 90 parts by weight of the Uji extract mixture, 2 to 8 parts by weight of shark cartilage extract, 2 to 8 parts by weight of Hagocho extract and 2 to 8 parts by weight of St. John's wort extract.

The Uji extract mixture comprises 30 wt% glucosamine, 69 wt% Uji extract and 1 wt% silicon dioxide.

The action of each component in the composition of the present invention is described in detail.

The main component of Beef Tallow Extract is CMO (Cetyl Myristoleate; cerasomal cis-9-cetylmyristoleate), a complex of fatty acids, extracted from connective tissue of animals such as cattle, and found in small amounts in plants. In the early 1970s, Diel found that CMOs helped arthritis a lot. Unlike conventional arthritis or rheumatoid medicines, CMOs are used as joint and rheumatic aids by helping the damaged immune system to normalize and fundamentally prevent symptoms from worsening.

Glucosamine is a substance composed of amino acids called glutamine in glucose and is an important component of body tissues including cartilage, skin, nails and hair. Glucosamine is a representative natural amino sugar widely distributed as important biological components such as glycoproteins, glycolipids, and mucopolysaccharides. Glucosamine exists as a structural unit in the sugar chains of various complex saccharides in vivo. Representative of these are proteoglycans containing mucopolysaccharides of chondroitin sulfate and hyaluronic acid, and are widely distributed in comprehensive tissues, skin tissues, cartilage and joint fluids. They have high moisturizing effect, maintain cell function and shape, and play important functions in cell surface such as lubrication, cell adhesion, proliferation and differentiation. Glucosamine is used in the form of salts for the treatment of osteoarthritis in Europe and the like. In the United States, it has been sold as a nutritional supplement for five to six years ago, forming a large market. In Japan, it has been listed as a food additive for a long time. It is used as a food material for athletes who suffer from joints, the elderly, the elderly, and patients suffering from arthritis.

Silicon dioxide (SiO ₂ ) is a component in various silicates that exist naturally. It is called silicon dioxide and is used as an anti-caking agent. When used as an anti-caking agent, the amount of silicon dioxide and the preparations containing it should be less than 2% of the food.

Shark cartilage is composed of ash, protein, carbohydrates, moisture, fiber, and phosphorus. Shark cartilage contains a component called chondroitin sulfate, which is part of a huge protein that makes cartilage elastic. Chondroitin sulfate has been reported to relieve the pain of mild osteoarthritis and slow the degeneration of cartilage to the same extent as nonsteroidal arthritis drugs such as aspirin and ibuprofen. Shark cartilage is also known to act as angiogenesis inhibitors (Lee, A. and Langer, R. Science , 221, 1185-1187, 1983).

Xia Ku Cao (Xia Ku Cao) is an orchard of nectar and related plants that is a toxic herbal medicine that has been harvested in the summer and dried in the sun and used as a medicinal herb. It has been widely used in various inflammations such as boils, wounds, bronchitis, mastitis, tonsillitis, and gingival fluids, and it also removes moist secrets, resulting in cold and cold hands and feet, pain in the knees, and pain in the lower back and shoulders. In addition, the whole body is weak and has been used as a prophylactic or herbal powder for the treatment of symptoms such as fat pain. These symptoms are similar to those of general arthritis including chronic rheumatoid arthritis in the modern pathological concept, and the substance extracted from hawacho is used for the treatment of general arthritis. The components of the vinegar include saponins such as oleanolic acid and ursolic acid, carotene, vitamin C, vitamine K, tannin, and caffeine ( caffeic acid), chlorogenic acid, etc. are known, and the presence of rosmarinic acid is also known [Korea useful plant resource research exhibition, Korea Research Institute of Chemical Technology, pp480-482 (1988); Studies on Chemical Compositions of Hagocho, Lee Jak-pyeong and 3 others, Beijing Medical University Journal, 17 (4), pp297-299 (1985); Pharm. Acta. Helv. 66. No. 7, pp 185-188 (1991).

St. John's wort refers to the ground above the plant called Hypericum perforatum, which is used as a neuro stabilizer to treat mild depression. As an active ingredient, it is a light-sensitive pigment containing hypericin and hyperforin, and has a mechanism of inhibiting serotonin reuptake.

The preparation method of the composition according to the present invention is as follows.

The bovine adipose tissue is washed thoroughly and then dried first at about 40 ° C. Finely crush the dried bovine adipose tissue and extract hot water at 120 ° C. for 4 hours. The extract is filtered, concentrated under reduced pressure and lyophilized to obtain a powdered Uji extract. 30% by weight of glucosamine and 1% by weight of silicon dioxide were added and mixed to obtain a Uji extract mixture.

After removing meat, foreign substances, etc. from the shark cartilage raw material completely, and washing it cleanly, it is first dried at about 40 ° C. using a low temperature drying method. The dried shark cartilage is hydrothermally extracted at 120 ° C. for 4 hours and enzymatically treated at 56 ° C. for 4 hours. First sterilize at 95 ° C. for 20 minutes and first filter with 100 mesh sieve. The filtrate is concentrated in vacuo and again sterilized for 30 minutes at 8 ° C., followed by secondary filtration through 150 mesh sieves. After spray drying the filtrate, it is filtered through a 100 mesh sieve to obtain a concentrated shark cartilage extract.

1 liter of water is added to the finely sliced red pepper paste, and hot water is extracted for 5 hours while stirring well. Collect the filtrate, collect the residue, add 2 liters of water, extract it for 3 hours, and re-heat the extract. The same amount of saturated n-butyl alcohol was added thereto, and the layers were separated three times, and only n-butyl alcohol was collected to 65 ° C, and concentrated under reduced pressure until the vinegar extract was dried. Most of n-butyl alcohol and water are evaporated, 100 ml of water is added, the azeotropic concentration is repeated, and then repeated twice. Finally, the same amount of distilled water is added and suspended, followed by freeze-drying to obtain powdered haejucho extract. .

The St. John's wort is finely chopped, washed and extracted with hot water in the same manner as the Hachocho extract to obtain St. John's wort in powder form.

Uji extract mixture, shark cartilage extract, hachocho extract, St. John's wort extract prepared above is mixed to prepare an extract mixture.

The extract mixture of the present invention has a 62.6 ± 0.71% activity suppression of hyaluronides, and significantly inhibits the activity of hyaluronides than the Uji extract mixture or shark cartilage extract.

In addition, the extract mixture of the present invention exhibited analgesic effects of 30.3%, 45.2%, 53.6% and 70.5% at 30 minutes, 1 hour, 2 hours and 3 hours, respectively, when administered at a concentration of 500 mg / kg, When administered at the mg / kg concentration, the analgesic effect of 55.1%, 66.7% and 82.3% at 1 hour, 2 hours and 3 hours, respectively, it can be seen that the analgesic effect is proportional to time and concentration.

Therefore, the composition of the present invention can be usefully used for the prevention and treatment of degenerative arthritis.

The composition of the present invention may further contain one or more active ingredients exhibiting the same or similar functions in addition to the extract mixture.

The extract mixture may be administered orally or parenterally during clinical administration and may be used in the form of a general pharmaceutical formulation. That is, the extract mixture of the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants that are commonly used, or Formulated using excipients. Solid preparations for oral administration include tablets, pills, powders, granules and capsules, and the like, which may be used in mixed herbal extracts, including at least one excipient such as starch, calcium carbonate, sucrose, lactose and gelatin, and the like. Are mixed to prepare. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral administration include suspensions, solutions, 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. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and the suspension solvent, 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, glycerol, gelatin and the like can be used.

The dosage varies depending on the weight, age, sex, health condition, diet, time of administration, method of administration, excretion rate and severity of the disease of the patient, and the daily dosage of the extract mixture of the present invention is 10-50 mg. / Kg (1,000 to 3,000 mg per day) and may be administered 1 to 6 times a day.

As a result of toxicity experiments by orally administering the extract mixture of the present invention to rats, the 50% lethal dose (LD ₅₀ ) by the oral dose toxicity test is determined to be a safe substance of at least 1 g / kg or more.

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 prevention and treatment of degenerative arthritis.

The composition of the present invention may be added to health food for the purpose of improving degenerative arthritis. When the extract mixture of the present invention is used as a food additive, the extract mixture may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, in the preparation of food or beverage, the mixed herbal extract of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less based on the raw material. However, in the case of long-term intake for health and hygiene or health control, the amount 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 food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, as in the general beverage. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, maltose, disaccharides such as sucrose, and polysaccharides such as dextrin, cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acid. Carbonating agents and the like used in beverages. In addition, the composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred examples and experimental examples are presented to help understand the present invention. However, the following Examples and Experimental Examples are provided only to more easily understand the present invention, and the contents of the present invention are not limited by the Examples.

Example  Preparation of Extract Mixtures of the Invention

1. Preparation of Uji Extract Mixture

Bovine adipose tissue was washed thoroughly and then dried first at about 40 ℃. After pulverizing the fat tissue of the dried cow fine, hot water was extracted for 4 hours at 120 ℃. The extract was filtered and concentrated under reduced pressure. The concentrate was lyophilized to give a powdered Uji extract.

In 69% by weight of the Uji extract, 30% by weight of glucosamine and 1% by weight of silicon dioxide were added and mixed.

2. Preparation of Shark Cartilage Extract

The flesh, foreign matters, and the like were completely removed from the fresh shark cartilage raw material, washed thoroughly, and dried first at about 40 ° C. using a low temperature drying method. The dried shark cartilage was ground into small particles using a hammer milling machine (Chopping). The ground shark cartilage pieces were extracted with hot water at 120 ° C. for 4 hours and enzymatically treated at 56 ° C. for 4 hours. Primary sterilization at 95 ° C. for 20 minutes and primary filtration through a 100 mesh sieve. The filtrate was concentrated in vacuo, and then sterilized again at 8 ° C. for 30 minutes and filtered secondly with a 150 mesh sieve. After the filtrate was spray dried, it was filtered through a 100 mesh sieve to obtain a concentrated powdered shark cartilage extract.

3. Preparation of Garlic Extract

After mixing 250 g of finely chopped vinegar about 3.0 cm, 2 liters of water was added thereto, followed by hot water extraction while stirring well. The filtrate was collected and collected, and the residue was extracted with 2 liters of water and reheated for 3 hours. The filtrates were combined and concentrated to 1 liter. The same amount of saturated n-butyl alcohol was added thereto, and the layers were separated three times. Then, only n-butyl alcohol was collected to 65 DEG C, and concentrated under reduced pressure until the vinegar extract was dried. After most of n-butyl alcohol and water were evaporated, 100 ml of water was added, the azeotropic concentration was added, and the resultant was repeated twice. Finally, the same amount of distilled water was added and suspended, followed by freeze-drying to obtain a powdered haejucho extract. .

4. Preparation of St. John's wort Extract

The St. John's wort was finely chopped, washed and then hot water extracted in the same manner as in the above 3 method to obtain St. John's wort extract in powder form.

5. Preparation of Extraction Mixture

The extract mixture was prepared by mixing 84.5 parts by weight of the prepared Uji extract mixture, 5 parts by weight of shark cartilage extract, 5 parts by weight of hyacinth extract, and 5 parts by weight of St. John's wort extract.

The extract mixture was dissolved in DMSO and used in the following experiment.

Experimental Example 1  : Determination of Hyaluronidase Activity Inhibition of Extract Mixtures of the Present Invention

In order to determine the inhibition of hyaluronidase activity of the extract mixture of the present invention, the activity was measured using the Morgan-Elson Assay method.

The hyaluronic acid dissolved in phosphate buffer solution and the extract mixture prepared in Example dissolved in DMSO were put in each and incubated at 37 ° C. for 20 minutes. After incubation, the compound 48/80 solution was added and then secondary cultured. After hyaluronic acid was added to the 3rd culture, K ₃ BO ₃ was added thereto, and the reaction was stopped by heating in a boiling water. After centrifugation, N-acetylglucosamine (N-acetylglucosamine) produced by the decomposition of hyaluronic acid by hyaluronates was verified by colorimetric determination at 585 nm using DM-AB (p-dimetylaminobenzaldehyde).

The results are shown in Table 1.

Extract Mixtures of the Invention (Examples) Uji Extract Mixture Shark Cartilage Extract % Activity inhibition 62.6 ± 0.71 53.0 ± 0.28 30.6 ± 0.07

As shown in Table 1, the extraction mixture of the present invention is 62.6 ± 0.71% of the inhibitory activity of hyaluronides, it can be seen that significantly inhibits the activity of hyaluronidase than the Uji extract mixture or shark cartilage extract.

Experimental Example 2  : Effect of Extraction Mixture of the Invention on the Proliferation and Extracellular Matrix Synthesis of Articular Chondrocytes (C28 / I2 Cells)

In order to investigate the effect of the extract mixture of the present invention on the hyaluronicase enzyme inhibitory activity and the extracellular matrix synthesis of chondrocytes on human costal chondrocytes, collagen type II, which is a specific extracellular matrix of cartilage Expression of was confirmed through RT-PCR.

Human rib chondrocytes were cultured in 1) control group (chondrocytes), 2) hyaluronidase treatment group, 3) the extract mixture of the present invention and hyaluronidase treatment group, and observed for 24 to 72 hours after treatment. .

After removing monolayer cultured chondrocytes, total RNA was isolated using Trizol Reagent (RNA extraction Kit, GIBCOBRL). The same amount of RNA for each group was generated by complementary DNA (cDNA) using AMV reverse transcriptase (BMS), and then prepared as primers for the respective primers for collagen type II and GAPDH and amplified by PCR. After the change was confirmed by electrophoresis on the agarose gel.

The results are shown in FIG.

As shown in Figure 1, it was confirmed that the extract mixture of the present invention is significantly expressed in chondrocyte collagen type II expression than the hyaluronidase alone treatment group.

Thus, it can be seen that the extract mixture of the present invention inhibits the activity of hyaluronides.

Experimental Example 3  : Pain Effect Experiment

In order to confirm the pain effect of the extract mixture of the present invention, the following experiment was carried out according to the method of Randall and LO Salito (Randall, LO and Salitto, JJ, Arch. Int. Pharmacodyn. Ther ., 111, 4.9-19, 1971). Was performed.

Pain effect experiments were based on the increased sensitivity to pain in the inflammatory site and its increased sensitivity to inhibition by analgesics.

Eight Sprague-Douri male rats weighing 180-220 g were used as experimental animals. After overnight fasting, the rats that did not respond to 300 g of pressure were first excluded using an analgesymeter (Ugo Basile, Italy). 0.1 ml of 20% brewers yeast-physiological saline suspension was injected subcutaneously into the soles of rats to cause inflammation, and after 2 hours, the extract mixture prepared in the above example was prepared at a concentration of 500 mg / kg and 1,000 mg / kg. Each was administered. After 0, 0.5, 1, 2, 3 hours, the pain threshold (g) was measured with an analyte. The pain threshold was gradually applied to the foot of the rat at a rate of 16 g / sec, and the pain response was when the rat tried to pull out the foot or twisted the body because of pain. Analgesic activity was expressed by obtaining% of control pain threshold. Ibuprofen (200 mg / kg) was used as a control drug.

The results are shown in Table 2.

% Pain over time 30 minutes 1 hours 2 hours 3 hours Reference Drug (Ibuprofen) 30.2 43.5 51.4 69.1 Extract Mixtures of the Invention (Examples) 500 mg / kg 30.3 45.2 53.6 70.5 1,000mg / kg 35.7 55.1 66.7 82.3

As shown in Table 2, when the extract mixture of the present invention was administered at a concentration of 500 mg / kg, the genes of 30.3%, 45.2%, 53.6% and 70.5% at 30 minutes, 1 hour, 2 hours and 3 hours respectively When the extract mixture of the present invention was administered at a concentration of 1,000 mg / kg, the analgesic effects of 55.1%, 66.7% and 82.3% were observed at 1 hour, 2 hours and 3 hours, respectively. Therefore, it can be seen that the extract mixture of the present invention exhibits an analgesic reduction effect in proportion to time and concentration.

Experimental Example 4  : Acute Toxicity of Oral Administration in Rats

In order to determine the acute toxicity of the extract mixture of the present invention, an acute toxicity test was conducted in the following manner.

Acute toxicity test was conducted using 6-week-old specific pathogen-free (SPF) SD rats. Two animals per group were suspended in a 0.5% methylcellulose solution in an extract mixture prepared in the above example and administered once orally at a dose of 1 g / kg / ml. 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 observe abdominal and thoracic organ abnormalities.

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.

Therefore, the extract mixture of the present invention does not show a change in toxicity even in rats up to 1 g / kg, oral administration minimum dose (LD ₅₀ ) was determined to be a safe substance of more than 1 g / kg extract.

Examples of preparations for the compositions of the present invention are illustrated below.

Formulation Example 1  : Preparation of Pharmaceutical Formulations

1. Preparation of powder

2 g extract mixture of the above example

1g lactose

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

2. Preparation of Tablets

100 mg of the extraction mixture of the above example

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

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

3. Preparation of Capsule

100 mg of the extraction mixture of the above example

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

Formulation Example 2  : Manufacture of food

Foods comprising the extract mixture of the present invention were prepared as follows.

1. Preparation of Cooking Seasonings

20 to 95% by weight of the extract mixture of the present invention was prepared for health promotion cooking seasoning.

2. Preparation of Tomato Ketchup and Sauce

0.2 to 1.0% by weight of the extraction mixture of the present invention was added to tomato ketchup or sauce to prepare tomato ketchup or sauce for health promotion.

3. Manufacturing of Flour Foods

0.5 to 5.0% by weight of the extract mixture of the present invention was added to flour, and bread, cake, cookies, crackers and noodles were prepared using the mixture to prepare foods for health promotion.

4. Preparation of soups and gravy

0.1 to 5.0% by weight of the extract mixture of the present invention was added to soups and broths to prepare meat products for health promotion, soups of noodles and broths.

5. Preparation of Ground Beef

10% by weight of the extract mixture of the present invention was added to the ground beef to prepare a ground beef for health promotion.

6. Manufacture of Dairy Products

5-10% by weight of the extract mixture of the present invention was added to milk, and the milk was used to prepare various dairy products such as butter and ice cream.

7. Manufacture of wire

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh using a grinder.

Black beans, black sesame seeds, and perilla were also steamed and dried by a known method, and then ground to a powder having a particle size of 60 mesh.

The extraction mixture of the present invention was decompressed and concentrated in a vacuum concentrator, and the dried product obtained by drying with a sprayer and a hot air dryer was pulverized with a particle size of 60 mesh using a grinder to obtain a dry powder.

The dry powders of the grains, seeds and extract mixtures prepared above were formulated in the following proportions.

Cereals (30% by weight brown rice, 15% by weight radish, 20% by weight barley),

Seeds (7% by weight perilla, 8% by weight black beans, 7% by weight black sesame),

Dry powder of the extraction mixture (3% by weight),

Ganoderma lucidum (0.5% by weight),

Foxglove (0.5 wt%)

Formulation Example 3  : Preparation of Beverages

1. Preparation of Carbonated Drinks

5-10% of sugar, 0.05-0.3% citric acid, 0.005-0.02% caramel, 0.1-1% of vitamin C are mixed, and 79-94% purified water is mixed to make syrup, and the syrup is 85-98 Sterilizing at 20 ℃ for 180 seconds, mixed with a cooling water 1: 1 ratio, and then injected with 0.5 to 0.82% carbon dioxide gas to prepare a carbonated beverage containing the extract mixture of the present invention.

2. Manufacture of health drinks

Instant sterilization by homogeneously mixing the subsidiary ingredients such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), water (75%) and extract mixture Health drinks were prepared by packaging in small packaging containers such as plastic bottles.

3. Preparation of Vegetable Juice

5 g of the extract mixture of the present invention was added to 1,000 ml of tomato or carrot juice to prepare a vegetable juice for health promotion.

4. Preparation of Fruit Juice

1 g of the extract mixture of the present invention was added to 1,000 ml of apple or grape juice to prepare fruit juice for health promotion.

The composition of the present invention significantly inhibits the activity of hyaluronidase and significantly reduces pain, and thus can be used as a medicine and health food useful for the prevention and treatment of degenerative arthritis.

Claims (6)

Prevention and treatment of degenerative arthritis, including 80 to 90 parts by weight of Uji extract mixture, including glucosamine and tallow extract, 2 to 8 parts by weight of shark cartilage extract, 2 to 8 parts by weight of hyacinth extract and 2 to 8 parts by weight of St. John's wort extract Pharmaceutical composition for. The pharmaceutical composition for preventing and treating degenerative arthritis according to claim 1, wherein the composition comprises 84.5 parts by weight of the Uji extract mixture, 5 parts by weight of shark cartilage extract, 5 parts by weight of hyacinth extract, and 5 parts by weight of St. John's wort extract. The pharmaceutical composition for preventing and treating degenerative arthritis according to claim 1 or 2, wherein the Uji extract mixture comprises 69% by weight of Uji extract, 30% by weight of glucosamine and 1% by weight of silicon dioxide. Prevention and improvement of degenerative arthritis, including 80 to 90 parts by weight of Uji extract mixture, including glucosamine and tallow extract, 2 to 8 parts by weight of shark cartilage extract, 2 to 8 parts by weight of Higocho extract and 2 to 8 parts by weight of St. John's wort extract Health food composition for. The degenerative arthritis preventing and improving health food composition according to claim 4, wherein the composition comprises 84.5 parts by weight of the Uji extract mixture, 5 parts by weight of the shark cartilage extract, 5 parts by weight of the vinegar extract and 5 parts by weight of St. John's wort extract. The degenerative arthritis prevention and improvement health food composition of claim 4 or 5, wherein the Uji extract mixture comprises 69% by weight of Uji extract, 30% by weight of glucosamine and 1% by weight of silicon dioxide.

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