KR101018403B1 - composition comprising the extract of soybean leaves for the prevention?delay or treatment of gout - Google Patents

Abstract

The present invention relates to a composition for preventing, delaying or treating gout containing soybean leaves extract as an active ingredient. Specifically, the soybean leaf extract extracted with water, alcohol or a mixture thereof as a solvent is uric acid in blood. By having a lowering effect of can be usefully used as a component of a pharmaceutical composition or dietary supplement for the prevention, delay or treatment of gout.

Soybean Leaf Extract, Hyperuricemia, Gout.

Description

Composition comprising the extract of soybean leaves for the prevention, delay or treatment of gout}

The present invention relates to a composition for preventing, delaying or treating gout comprising soybean leaf extract as an active ingredient.

Gout is a term that refers to various groups of diseases found only in humans and is an articular disease caused by an increase in the concentration of tissues and blood uric acid. In gout patients, hyperuricemia, recurrent symptoms of acute arthritis, the presence of monosodium urate crystals in synovial fluid leukocytes, and the formation of monosodium urate crystal masses in and around joints It is a disease that causes deposition and consequent malformations and disorders of the joints and is accompanied by kidney disease. Gout is called 'King of Diseases' and 'Kings of Kings' and is a disease that occurs more frequently with age, and is accompanied by great pain due to the inflammatory response caused by the uric acid crystal of the big toe area.

The symptoms of gout in our body are not asymptomatic at first, but gradually progress to degeneration of human tissues, which causes severe subjective symptoms. As a first stage of onset, the joints of the limbs feel severe pain at night and wake up sleeping, and the second stage of the onset causes pain and can't stand up or walk. appear. In addition, these symptoms may recur after one week and then recur. In addition, uric acid stones, diabetes mellitus, obesity, hypertension, arteriosclerosis, or uremia are shown as complication stages (Kim Yong-seo, Gout, Oriental Medicine and Health, 151-154, 2001).

Hyperuricemia, the cause of gout, is an increase in the concentration of uric acid in the blood and occurs when the concentration of monosodium urate in serum exceeds the limit of solubility. At 37 ° C., the uric acid saturation of plasma is about 7 mg / dl. Therefore, if this concentration is exceeded, it becomes physicochemically supersaturated. Serum uric acid concentrations are known to be relatively high when they exceed +2 SD above the average serum uric acid concentration of normal subjects. In most epidemiological studies, the upper limit for men is 7.0 mg / dl and for women 6.0 mg / dl. For this reason, the substantial upper limit for hyperuricemia is defined as above 7.0 mg / dl.

Until now, as a gout treatment agent, an allopurinol drug is used as a therapeutic agent, but since it has many side effects, it is required to develop a safe and free natural substance. Thus, as a natural-derived gout therapeutic agent, a compound isolated from mushrooms (Korean Patent No. 10-0759467), purple pigment (Korean Patent No. 10-0759468) isolated from purple sweet potatoes, leek extract (Korean Patent No. 10-0527105), Jang Saeng Hong A mixture of bellflower extract (Korean Patent No. 10-0662206), refined fish oil, green tea extract, Western Lioness extract, kelp extract, Sanjoin extract and Ginkgo biloba extract (Korean Patent No. 10-0492470), and Cauliflower extract (Korean Patent Application No. 10-2004) -0080640) has been reported.

Beans are a year-old herb belonging to the legume family, and in the private sector, soy sauce is used to treat food poisoning caused by fish, and to feed soybeans to the first aid for the sounding caused by the stroke. If you drink it is effective. In oriental medicine, seeds are called soybean or black soybean, which are effective for blood circulation, diarrhea, wind, detoxification, diuresis, obedience, dead, jaundice, and tonic. The fermented soybeans obtained by steaming and fermenting black soybeans were always or freshwater, and were used for the effects of fever, sweating, health, number, nourishment, and heat exchange. , Female Press, 356).

Soybeans are not only rich in protein and lipids, but also contain a large amount of bioactive substances that are involved in physiological control, making them an important part of our diet. (Kwon TW, Korea soybean Digest 17 (1): 1-4 , 2000). There is a lot of research on the physiological activity of soybeans and low incidence of coronary heart disease, breast cancer, prostate cancer and colorectal cancer in the high intake of soybeans. Relevant (Messina MMV, J Ren Nutr 10 (2): 63-68, 2000; Barnes S et al. , Korea Soybean Digest 15 (2): 81-93, 1998). As such, many studies on soybeans are being conducted, but there are few studies on soybean leaves.

Soybean leaves are called soybean leaves or gwak and healed in forests and societies. They make young herbs and eat them, and they are used for ssam, kimchi and pickles. In particular, the soybean leaves are known as foods commonly used in the Gyeongsang-do area in the form of soybean leaf chanch and soybean kimchi. It can be eaten by picking soft young soybean leaves in summer and using water kimchi, or by cutting yellow deciduous soybean leaves in autumn and seasoning with salted fish. At this time, the physiological activity of blue bean leaf and deciduous yellow bean leaf is considered to be different. Soybean leaves are reported to contain sojagol (Keen NT et al. , Phytochemistry , 11: 1031-1039, 1972) and flavonoid compounds (Park Sung-jong, Master's Thesis, Sunchon, 2002). Among the flavonoid compounds, especially apigenin, a camphorol glycoside, afrormosin glycoside, and isoflavone components (pinitol, chiroinositol, genistein, daidzein), etc. are contained. (Keung et al. , Chemicobiological Interactions Interactions , 130-132: 919-930, 2000), decreased blood alcohol levels (Xie CI et al. , Alcoholism, Clinical and Experimental Research 18: 1443-1447, 1994), examples of bone loss Action (Ishida H et al. , Biol Pharm Bull 21: 62-66, 1998), MAO inhibitory activity (Keung WM & Vallee BL, Proc. Natl. Acad. Sci. USA, 95: 2195-2203, 1998), Benign prostatic hyperplasia, prostate cancer inhibitory activity (Geller J et al. , The prostate 34: 75-79, 1998), B16 melanoma inhibitory activity (Record IR et al. , Int J Cancer 72: 860-864, 1997), Antimutagenic activity (Miyazawa M et al. , J Agric Food Chem, 47: 1346-1349, 1997), antioxidant and antidiuretic activity (Vedavanam K et al. , Phytotherapy Research 13: 601-6 08, 1999), lipid peroxidation inhibitory activity (Toda S & Shirataki Y, Phytotherapy Research 13: 163-165, 1999). However, there are no reports that soybean leaves have the effect of preventing, delaying or treating hyperuricosis or gout.

Accordingly, the present inventors have completed the present invention by discovering that the soybean leaf extract can be usefully used for preventing, delaying or treating gout by confirming that it has a lowering effect of blood uric acid in diabetic model mice.

An object of the present invention is to provide a composition for preventing, delaying or treating gout, and health functional foods containing soybean leaf extract as an active ingredient.

In order to achieve the above object, the present invention provides a composition for preventing, delaying or treating gout containing soybean leaf extract as an active ingredient.

The present invention also provides a method for delaying or treating gout, comprising administering a pharmaceutically effective amount of the composition to a subject having gout.

The present invention also provides a method for preventing gout, comprising administering to a subject a pharmaceutically effective amount of said composition.

In addition, the present invention provides a health functional food for preventing, delaying or improving gout containing soybean leaf extract as an active ingredient.

Soybean leaf extract of the present invention can be usefully used as a component of a pharmaceutical composition or health functional food for the prevention, delay or treatment of gout by having a lowering effect of uric acid in the blood.

Hereinafter, terms used in the present invention are defined.

As used herein, the terms "prevention" and "delay" refer to any action that inhibits the symptoms or delays the progression of gout with administration of the composition of the present invention.

As used herein, the terms "treatment" and "improvement" refer to any action in which the symptoms of gout improve or benefit from administration of a composition of the present invention.

As used herein, the term "administration" means providing a subject with any of the compositions of the present invention in any suitable manner.

As used herein, the term "individual" means any animal, such as a human, monkey, dog, goat, pig or rat, having a disease in which the symptoms of gout may be improved by administering the composition of the present invention.

As used herein, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, which means the type of disease, the severity, the activity of the drug, the drug Sensitivity to, time of administration, route of administration and rate of administration, duration of treatment, factors including drug used concurrently, and other factors well known in the medical arts.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for preventing, delaying or treating gout containing soybean leaf extract as an active ingredient.

The gout is preferably caused by hyperuricosis, but is not limited thereto.

The bean leaf extract is

1) extracting the dried soybean leaves into powder and then adding an extraction solvent;

2) filtering the extract of step 1); And

3) It is preferably prepared by a manufacturing method including the step of concentrating the extract of step 2) and freeze drying, but not limited to the above method, hot water extraction, shaking extraction, ultrasonic extraction, Soxhlet extraction and reflux extraction, etc. Any conventional extraction method in the art can be used.

In the above method, the soybean leaves of step 1) include both those obtained when the leaves are green or yellow, and excludes soybean leaves immersed in commercially available salt water. After collecting the soybean leaves, it is preferable to use the dried after washing with water to remove foreign substances and salts, but is not limited thereto.

The extraction solvent is preferably extracted with water, lower alcohols of C ₁ ~ C ₄ or mixed solvents thereof, and more preferably extracted with lower alcohols of C ₁ ~ C ₄ , but is not limited thereto. The lower alcohol is preferably ethanol or methanol, but is not limited thereto.

The volume of the extraction solvent is preferably extracted by adding 2 to 15 times the volume of the pulverized bean leaf, and more preferably, 5 to 10 times to add the extract, but is not limited thereto. The extraction temperature is preferably 20 ° C to 100 ° C, more preferably 40 ° C to 80 ° C, but is not limited thereto. The extraction time is preferably 1 to 5 days, more preferably 2 to 3 days, but is not limited thereto. The number of extraction is preferably repeated extraction 1 to 3 times, but is not limited thereto. The extraction method may be any one of hot water extraction, shaking extraction, reflux extraction, or Soxhlet extraction, but is not limited thereto.

In the present invention, the dried soybean leaf was pulverized to a suitable size, put into a extraction container, put a solvent and extracted using an ultrasonic wave, filtered with a filter paper, and then concentrated and lyophilized to obtain a soybean leaf extract.

In the present invention, in order to determine whether the soybean leaf extract has an effect of lowering uric acid in blood, blood lacquer was collected after ingesting a diet in which the soybean leaf extract was added to male db / db mice about 4 weeks old, and the content of blood uric acid was measured. As a result, the experimental group ingested with soybean leaf extract showed about 59-57% lower blood uric acid than the control group (see Table 2).

In addition, it is apparent that soybean leaves have been edible since ancient times and are not toxic to their extracts.

Therefore, the soybean leaf extract of the present invention has an excellent effect of lowering the urine acid in the blood and is judged to be very safe without side effects, and thus can be usefully used for preventing, delaying or treating gout.

The composition of the present invention may further contain one or more active ingredients exhibiting the same or similar function, and may further comprise chiroinositol or genistein, which is known to exhibit a uric acid lowering effect.

The present invention may comprise a pharmaceutically acceptable carrier, excipient or diluent.

The compositions of the present invention may be in various oral or parenteral formulations. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups. In addition to the commonly used simple diluents, water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, 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, glycerogelatin and the like can be used.

The subject to which the pharmaceutical composition of the present invention can be applied is preferably a vertebrate, and more preferably a mammal such as a rat, mouse, rabbit, guinea pig, hamster, dog, cat, chimpanzee or gorilla, but is not limited thereto. .

The present invention also provides a method for delaying or treating gout, comprising administering a pharmaceutically effective amount of the composition to a subject having gout.

The present invention also provides a method for preventing gout, comprising administering to a subject a pharmaceutically effective amount of said composition.

The gout is preferably caused by hyperuricosis, but is not limited thereto.

Soybean leaf extract of the present invention has an excellent effect of lowering the urine acid in the blood and is determined to be very safe without side effects, it can be seen that it can be useful for gout prevention, delay or treatment.

The composition of the present invention may further contain one or more active ingredients exhibiting the same or similar function, and may further comprise chiroinositol or genistein, which is known to exhibit a uric acid lowering effect.

The composition of the present invention may be administered orally or parenterally, and it is preferable to select externally or intraperitoneally, rectally, intravenously, intramuscularly, subcutaneously, intrauterine epidural or cerebrovascular injection methods for parenteral administration. Preferably for oral administration.

Dosage units may contain, for example, one, two, three or four times the individual dosage, or they may contain 1/2, 1/3 or 1/4 times. The individual dosage preferably contains an amount in which the effective drug is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dose. The effective dose of the composition of the present invention is 0.0001 to 10 g / kg, preferably 0.001 g to 1 g / kg, may be administered 1 to 6 times a day.

The composition of the present invention can be used alone or in combination with methods for using surgery, hormone therapy, chemotherapy and biological response modifiers for the prevention, delay or treatment of gout.

In addition, the present invention provides a health functional food for preventing, delaying or improving gout containing soybean leaf extract as an active ingredient.

The gout is preferably caused by hyperuricosis, but is not limited thereto.

Soybean leaf extract of the present invention has an excellent effect of lowering the urine acid in the blood and is judged to be very safe without side effects, it can be seen that it can be useful for preventing, delaying or improving gout.

The functional food according to the present invention may be, for example, various functional foods such as chewing gum, caramel products, candy, ice cream, confectionery, beverage products such as soft drinks, mineral water, alcoholic beverages, and health functional foods including vitamins and minerals. Can be.

The soybean leaf extract of the present invention may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or hygiene). In general, in the preparation of food or beverage, the soybean leaf extract of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less with respect to the raw material. However, in the case of long-term intake for health and hygiene or health control purposes, 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.

The functional food of the present invention may contain various flavors, natural carbohydrates, and the like as additional ingredients. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is preferably selected in the range of 0.01 to 0.04 parts by weight, preferably about 0.02 to 0.03 parts by weight, per 100 parts by weight of the health food of the present invention.

In addition to the above, the functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. In addition, the functional food of the present invention may contain fruit flesh for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The ratio 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 health food of the present invention.

Hereinafter, the present invention will be described in detail with reference to Examples, Experimental Examples and Preparation Examples.

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

Example 1 Preparation of Soybean Leaf Water Extract

Soybean leaves purchased from the National Agricultural Cooperative Federation were washed, dried completely using a dryer, and finely chopped. 100 g of finely chopped soybean leaves were immersed in 10 times of water, that is, 1 L, extracted with hot water for 24 hours and repeated three times. The extract was cooled, and the solvent of the supernatant obtained after filtration was evaporated in vacuo to concentrate the extract. The yield was 74.2% (w / w).

Example 2 Preparation of Soybean Leaf Ethanol Extract

The finely chopped soybean leaves were immersed in 10-fold 100% ethanol (HPLC grade) as in <Example 1> and extracted using a sonicator (Branson Ultrasonics corporation, USA) for 3 days at room temperature. After the filtration process, the solvent of the obtained supernatant was evaporated in vacuo to concentrate the extract. The yield was 79.5% (w / w).

Example 3 Preparation of 70% Ethanol Extract of Soybean Leaf

Extract was obtained by the method of <Example 2> using 70% aqueous ethanol solution (HPLC grade). The yield was 82.3% (w / w).

Example 4 Preparation of Soybean Leaf Methanol Extract

Extract was obtained by the method of <Example 2> using 100% methanol (HPLC grade). The yield was 83.76% (w / w).

Experimental Example 1 Lowering Effect of Blood Uric Acid

Male db / db mice (Oriental Bio, Korea), 4 weeks old, were divided into two groups, and 1% soybean leaf water, ethanol, aqueous ethanol solution and methanol extract were added to AIN-93 diet normal diet (Table 1) and drinking water. One diet was taken free diet for six weeks. Animals fasted 12 hours at 6 weeks of dietary ingestion were sacrificed by cardiac sampling to collect blood. After plasma was separated from blood, the content of uric acid in blood was measured using a Hitachi 7600-110 analyzer (Hitachi, Japan).

AIN-93 diet normal dietary composition (%) ingredient content(%) Casein 14.0 L-cysteine 0.18 Corn starch 46.6 Hojeong Corn Starch 15.5 Sugar 10.0 fibrin 5.0 Soybean oil 4.0 AIN-93 synthetic mineral 3.5 AIN-93 Multivitamin 1.0 Choline Hydrogen Tartrate 0.25 Tertiarybutylhydroquinone (mg) 0.8 lard 0

Degree of inhibition of uric acid in blood Kinds Blood uric acid (mg / dl) Inhibition of uric acid in blood (%) Control 2.32 0 Soybean Leaf Water Extract 0.99 57.32 Soybean Leaf Ethanol Extract 0.90 61.21 Soybean Leaf Extract 70% Ethanol Solution 0.97 58.18 Soybean Leaf Methanol Extract 0.99 57.33

As a result, as shown in Table 2, the experimental group to which the soybean leaf extract was added showed a blood uric acid lowering effect of about 59% to 57% compared to the control group (Table 2).

The preparation examples for the compositions of the present invention are illustrated below.

Preparation Example 1 Preparation of a Pharmaceutical Formulation

1. Preparation of powder

2 g extract of Example 2

1 g lactose

The above components were mixed and packed in airtight bags to prepare powders.

2. Preparation of Tablets

100 mg of extract of Example 2

Corn starch 100 mg

100 mg of milk

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 extract of Example 3

Corn starch 100 mg

100 mg of milk

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.

4. Manufacture of rings

1 g extract of Example 4

Lactose 1.5 g

Glycerin 1 g

0.5 g of xylitol

After mixing the above components, it was prepared to be 4 g per ring in a conventional manner.

5. Manufacture of granules

150 mg of extract of Example 4

Soy extract 50 mg

Glucose 200 mg

600 mg of starch

After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules, which were then filled into fabrics.

Preparation Example 2 Preparation of Food

1. Preparation of flour food

0.5 to 5.0 parts by weight of the extract of Example 3 of the present invention was added to the flour, using the mixture to prepare bread, cakes, cookies, crackers and noodles to prepare a health promoting food.

2. Preparation of soups and gravy

0.1 to 5.0 parts by weight of the extract of Example 3 of the present invention was added to soups and broths to prepare meat products for health promotion, soups of noodles and broths.

3. Preparation of Ground Beef

10 parts by weight of the extract of the extract of Example 3 of the present invention was added to the ground beef to prepare a ground beef for health promotion.

4. Manufacture of dairy products

5 to 10 parts by weight of the extract of Example 3 of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

5. Manufacture of wire

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh.

Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer.

The extract of Example 1 of the present invention was concentrated under reduced pressure in a vacuum concentrator, dried by spraying and drying with a hot air dryer, and then pulverized with a particle size of 60 mesh to obtain a dry powder.

The dry powders of the grains, seeds and extracts of Example 1 prepared above were formulated in the following ratios.

Cereals (30 parts by weight brown rice, 15 parts by weight brittle, 20 parts by weight of barley),

Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds)

Extract of Example 1 (3 parts by weight),

(0.5 part by weight),

Foxglove (0.5 part by weight)

Preparation Example 3 Preparation of Beverage

1. Manufacture of health drinks

Instantly mix the subsidiary ingredients such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), water (75%) and 5 g of the extract of Example 1 of the present invention. After sterilization, it was packaged in small packaging containers such as glass bottles and plastic bottles to prepare healthy drinks.

2. Preparation of Vegetable Juice

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

3. Preparation of Fruit Juice

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

The present invention can be usefully used for the development of therapeutic agents, herbal preparations, health supplements, health functional foods and beverages for the prevention, delay or treatment of gout using soybean leaf extract.

1 is a diagram showing the effect of lowering the blood uric acid of 100% ethanol extract of soybean leaves of the present invention.

Claims (13)

A composition for preventing, delaying or treating gout, which contains soybean leaves extract as an active ingredient. The method for preventing, delaying or treating gout of claim 1, wherein the soybean leaf extract is extracted with water, alcohol or a mixture thereof. 3. The composition for preventing, delaying or treating gout according to claim 2, wherein the alcohol is C ₁ to C ₄ lower alcohols. 4. The composition for preventing, delaying or treating gout according to claim 3, wherein the lower alcohol is ethanol or methanol. delete The composition for preventing, delaying or treating gout of claim 1, wherein the gout is caused by hyperuricosis. delete delete Health functional food for preventing, delaying or improving gout containing soybean leaf extract as an active ingredient. 10. The health functional food for preventing, delaying or improving gout according to claim 9, wherein the bean leaf extract is extracted with water, alcohol or a mixture thereof. 11. The dietary supplement for preventing, delaying or improving gout according to claim 10, wherein the alcohol is C ₁ to C ₄ lower alcohols. The health functional food for preventing, delaying or improving gout according to claim 11, wherein the lower alcohol is ethanol. 10. The dietary supplement for preventing, delaying or improving gout according to claim 9, wherein the gout is caused by hyperuricosis.

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