KR100543405B1 - Composition comprising the extract of Allium victorialis L. var. platyphyllum for treating or preventing diabetes mellitus - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of diabetes mellitus disease comprising the acid garlic extract as an active ingredient, the acid garlic extract exhibits anti-diabetic effect by significantly reducing plasma glucose (diabetic), thus diabetic It can be used as a pharmaceutical composition or health functional food useful for the prevention and treatment of diseases.

Diabetic Disease, Acid Garlic, Glucose, Pharmaceutical Composition, Health Functional Food

Description

Composition and composition for the prevention and treatment of diabetic diseases, including acid garlic extract as an active ingredient. platyphyllum for treating or preventing diabetes mellitus}

The present invention relates to a composition for the prevention and treatment of diabetic diseases containing acid garlic extract as an active ingredient.

Diabetes mellitus is when the physiological function of insulin released by β cells in the Langerhans islet in the pancreas is poor or the number of insulin-receptors is low, resulting in insufficient insulin physiological function. It is a symptom of hyperglycemia that occurs when urine has sugar detected. When diabetes is induced, the secretion state of insulin and glucagon is disturbed, causing abnormal metabolic control functions such as protein and lipid metabolism as well as carbohydrates, resulting in various metabolic diseases. Thickening of epithelial cell membranes causes many complications such as the circulatory system.

Diabetes mellitus is characterized by two types, type 1 diabetes mellitus, which is caused by a lack of secretion of insulin, a glucose-regulating hormone in the blood, mainly younger people in their 10s to 20s. It is also called juvenile diabetes because it develops in children. Type 2 diabetes mellitus occurs mainly after the age of 40, and occupies most of the diabetic patients in Korea. Unlike type 1, it is called adult-type diabetes and the cause of the disease is not clear yet, but it is known to be caused by genetic factors and environmental factors. The type 2 diabetes is caused by pancreatic beta cells. Both disorders and defects in insulin action (insulin resistance) in target cells are observed.

The most important goal in the treatment of diabetes is to control blood glucose levels as close to normal as possible, and therapies include pharmacotherapy, diet and exercise therapy. Oral hypoglycemic agents currently used in patients with type 1 and type 2 diabetes include α-glucosidase inhibitors, sulfonylurea preparations, and biguanide preparations. Cidase inhibitors show a therapeutic effect of diabetes by delaying the digestion and absorption of carbohydrates in the diet, thereby reducing the elevation of postprandial blood sugar and blood insulin. α-glucosidase inhibitors do not induce hyperinsulinemia or hypoglycemia and promote the secretion of glucagon-like peptide-1 in the small intestine that promotes insulin secretion and inhibits glucagon secretion. Have advantages (Mooradian, AD, Thurman, JE, Drugs, 57 , pp 19-29, 1999; Baron, AD Diabetes Research and Clinical Practice , 40 , ppS54-S55, 1998). Currently used in clinical trials include acarbose, avobolibose and miglitol, but prolonged use of α-glycosidase inhibitors may cause abdominal bloating, vomiting and diarrhea in some patients. Side effects may be observed and their use may be limited (Hanefeld M., Journal of Diabetes and its Complications, 12 , pp228-237, 1998).

To date, there is no cure for diabetes, and there are many researches to search for diabetes drugs from natural products due to the side effects of drug treatments, and WHO (1990) is effective for diabetes and has fewer side effects. The use of natural products is highly recommended (Grover JK, Vats. V., Rathi. SS, Journal of Ethnopharmacology, 73 , pp461-470, 2000).

Garlic mountains of the invention (Allium. Victorialis L. var. Platyphyllum MAKINO) is a plant of the lily (Liliaceae) that is found in the high mountains of South Korea Jirisan, Odaesan, Ulleungdo and elsewhere, and now a lot of wild specifically on Ulleungdo ever It is difficult to see large colonies elsewhere. The leaves and lichens of mountain garlic have been used not only as wild plants but also as herbs for the treatment of gastritis and heart disease (Moon, KS: Components and Use of Herbal Medicine, Scientific Encyclopedia., Pyongyang , pp671-672, 1984). Garlic leaves contain 2-3% carbohydrates and ascorbic acid, and phosphorus is known to contain sulfur-containing organic compounds (Lawson, LD et al., Journal of Natural Products , 54 , pp 436-444). , 1991). Sulfur-containing compounds contained in acid garlic exist in the form of S-alkenyl- or S-alkyl-L-cysteine, and activation of allinase occurs when the plant is damaged by tissue. This produces a volatile compound of disulfide that gives a garlic-like odor. These sulfur compounds have also been reported to exhibit platelet aggregation inhibitory activity (Wijaya, CH et al., Nat. Prod. Sci. , 2 , pp37-42, 1996; Liakopoulou-Kyriakides, M. et al., Phytochem. , 24 , pp 600-601, 1985).

The present inventors have conducted the exploration of the epidermis, microscopic structure, anatomical, pollen and cytological characteristics of wild garlic, and the morphological and hydrological classification by the native habitat (Yoogi Memory, Won-bae Kim, Hee-jun Park, Hak-tae Lim, Korean Society for Horticultural Science) , 39 , pp260-265, 1998: Organic Ego, Won-Bae Kim, Hee-Joon Park, Woo-Chul Lee, Hyung-Jeong Jang, Hyung-Jeong Jang, 11 , pp210-216, 1998), Gitogenin 3 as a component of spirostanol glycoside in acid garlic -O-Licotetroside (gitogenin 3-O-lycotetroside) is used as a flavonoid glycoside, aspartalin and cameferol 3,4'-di-O-β-D-glucoside ( kaempferol 3,4'-di-O-β-D-glucoside) has been isolated (Lee, KT et al., Archives of Pharmacal Research , 24 , pp44-50, 2001). In addition, the present inventors showed that the cytotoxicity of the acid garlic obtained by incubation than the simple alcohol extract showed greater cytotoxicity, and the isolated component Gitogenin 3-O-ricotetroside also showed strong cytotoxicity. The content of sulfur compounds in each part of the garlic was reported to be higher than that of the subterranean part (Park Hee-jun, Kim Won-bae, Organic Eum, Kwon Tae-tae, Korean Society of Plant Resources, 11 , pp51-60, 1998). ).

However, in spite of the above findings, continuous pharmacological efficacy test for acid garlic is required to industrialize acid garlic into functional food. The present inventors completed the present invention by confirming the excellent efficacy of the acid garlic as a result of measuring the anti-diabetic effect by using a diabetic animal model induced by streptozotocin to develop the acid garlic as a functional food.

An object of the present invention is to provide a pharmaceutical composition and health functional food for the prevention and treatment of diabetic diseases containing acid garlic extract showing an excellent anti-diabetic effect as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of diabetic diseases containing acid garlic extract as an active ingredient.

In addition, the extract provides a pharmaceutical composition that is an extract available in water, lower alcohols of C ₁ to C ₄ and mixed solvents thereof.

The diabetic disease also includes a combination of one or more of chronic hyperglycemia, atherosclerosis, microangiopathy, kidney disease, heart disease, diabetic retinopathy and other ophthalmic diseases. do.

Hereinafter, the present invention will be described in detail.

Acid garlic extract of the present invention can be obtained as follows.

After drying the leaves, the roots, the diameter and the outpost, preferably the leaves and the diameter of the acid garlic of the present invention, and then grinding and pulverizing, about 2 to 20 times the weight of the acid garlic, preferably about 5 to 10 A polar solvent of up to twice the volume of water and C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol or the like, or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably 20 2 to 5 repetitions using an extraction method such as hot water extraction, cold needle extraction, reflux cooling extraction, or ultrasonic extraction for about 3 hours to 1 day, preferably 5 hours at 100 ° C. Garlic methanol extract can be obtained.

In addition, the non-polar solvent soluble extract of the present invention, after suspending the crude extract in distilled water, the suspension is about 1 to 100 times, preferably about 1 to 5 times the volume of a polar solvent such as hexane, ethyl acetate, chloroform It can be obtained by extracting and separating the nonpolar solvent soluble layer once to 10 times, preferably 2 to 5 times by addition. It is also possible to further carry out conventional fractionation processes (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis, 3rd Ed. P6-7, 1998).

The present invention provides a composition for the prevention and treatment of diabetic diseases containing the acid garlic extract obtained by the above production method as an active ingredient.

The antidiabetic effect was measured with the acid garlic methanol extract obtained by the above process. As a result, oral administration of the leaf and cauliflower extract of acid garlic significantly lowered the plasma glucose content. It was confirmed that the effect is stronger than the extract.

The acid garlic of the present invention has been used as a herbal medicine and food for a long time, so there is almost no toxicity and side effects, so it can be used safely for long-term use for treatment and prevention purposes.

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. Liquid preparations for oral use may include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to water and liquid paraffin, which are commonly used to include suspensions, solutions, emulsions, and syrups. have. 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. Administration may be administered once a day or may be divided several times.

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 diabetic disease. Examples of the food to which the acid garlic extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

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

The health functional beverage composition of the present invention 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 said natural carbohydrate 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 composition 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, chocolate), pectic acid and salts thereof, alginic acid and the like. Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp 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 generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition 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 Mountain Garlic Extract

Mountain garlic grown in Taebaek-si, Gangwon-do is divided into leaves and diameter, and then dried and refluxed three times for 5 hours by adding methanol corresponding to 5 times the weight of each garlic powder (1kg) and diameter (1kg). Extracted. The resultant was concentrated under reduced pressure to obtain 242 g of mountain garlic leaf extract and 45 g of ginseng extract, which was suspended in 5% Tween 80 and used as a sample in the following experiment.

Experimental Example 1. Measurement of antidiabetic effect of acid garlic

1-1. Laboratory animals

Sprague-Dawley male rats with an average weight of 200 ± 10g were distributed from the Bio Link, and the temperature of 22 ± 1 ° C, 55 ± 3% humidity, and 12 hours contrast environment Adapted to solid feed for 1 week at.

Body weight change was measured at the start of the experiment and body weight change was measured for the initial weight on the last day, and water and feed intake were also measured 24 hours before the last day.

1-2. Diabetes

Streptozotocin was administered to the tail vein of experimental animals to induce diabetes. Streptozotocin 300 mg / kg was dissolved in 0.05M citrate buffer (pH 4.5). Diabetes induction was determined by taking blood from the tail vein in the fasting state 7 days after streptozotocin administration. Rats in the range of 300 to 450 mg / dL were selected and the garlic and leaf extracts of the garlic extract obtained in Example 1 were orally administered at a dose of 100 mg / kg and 200 mg / kg for 2 weeks. Fasted time ago.

1-3. Determination of Blood Glucose Content

Blood glucose content was measured using a commercially available Lipexan One Touch Test Strip (LIFESCAN, Milpitas, Calif., USA). After the sample was added, the experimental animal was lightly anesthetized with carbon dioxide, blood was collected from the abdominal aorta, and the amount of glucose in the blood was measured. Was isolated and used as an enzyme source.

As a result, diabetic rats treated with streptozotocin to induce diabetes mellitus lost weight, increased water intake, and increased diet. When the garlic extracts were orally administered as shown in Table 1, the symptoms of diabetes were suppressed, and the leaf extracts were more effective than the extracts of Arbor. In addition, the leaf and phosphorus extract was not active in the 100 mg / kg administration group, but showed a significant hypoglycemic effect in the 200 mg / kg administration group. Among the administration group, the administration group of the leaf extract 200mg / kg showed a 24.0% reduction effect, the administration group of the extract 200mg / kg showed a decrease effect of 17.2% (see Table 2).

process Dosage (mg / kg, p.o.) Weight change (g) Water intake (ml / day / rat) Dietary Intake (g / day / rat) Normal + 30.2 ± 2.48 ^a 30.6 ± 7.23 ^c 19.8 ± 2.17 ^c STZ -35.7 ± 6.23 ^c 129.4 ± 18.7 ^a 28.8 ± 3.29 ^a Leaf extract 100 -30.1 ± 7.56 ^bc 110.6 ± 9.54 ^ab 26.3 ± 4.15 ^ab 200 -25.2 ± 4.56 ^b 96.7 ± 7.63 ^b 21.5 ± 3.96 ^bc Phosphorus extract 100 -31.9 ± 6.96 ^bc 120.4 ± 15.9 ^a 27.9 ± 5.13 ^ab 200 -29.0 ± 4.28 ^bc 109.6 ± 6.43 ^ab 25.8 ± 2.18 ^abc

process Dosage (mg / kg, p.o.) Concentration (mg / dl) Inhibition Rate (%) Normal 93.7 ± 5.16 ^d 100 STZ 343.6 ± 12.8 ^a 0 Leaf extract 100 320.9 ± 20.6 ^{a, b} 9.1 200 283.7 ± 18.2 ^c 24.0 Phosphorus extract 100 330.2 ± 10.7 ^a 5.3 200 300.6 ± 18.8 ^{b, c} 17.2

Experimental Example 2. Statistical Processing

All experimental results were expressed as mean ± SD, and statistical analysis and significance analysis were performed using Duncan's new multiple range test.

The preparation example of the pharmaceutical composition containing the acid garlic extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.

Formulation Example 1 Preparation of Powder

Mountain Garlic Extract Dry Powder 300 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

Dry Garlic Extract Dry Powder 50 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

Dry Garlic Extract Dry Powder 50 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

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

Dry Garlic Extract Dry Powder 50 mg

Appropriate sterile distilled water for injection

pH adjuster

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

Mountain Garlic Extract Dry Powder 100 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

Mountain garlic extract dry powder 1000 mg

Vitamin Mixture

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B ₁ 0.13 mg

Vitamin B ₂ 0.15 mg

Vitamin B ₆ 0.5 mg

0.2 μg of vitamin B ₁₂

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 vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred embodiment, the composition 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

Mountain garlic extract dry powder 1000 mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components according to a conventional healthy beverage manufacturing method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized 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, since the acid garlic extract of the present invention exhibits excellent anti-diabetic effect, it can be used as a pharmaceutical composition and health functional food for the prevention and treatment of diabetic diseases.

Claims (5)

Acid garlic ( Allium. Victorialis L. var. Platyphyllum ) C ₁ to C ₄ Low alcohol extract containing a low alcohol extract as an active ingredient pharmaceutical composition for the prevention and treatment of diabetes. delete delete delete delete