KR101910898B1 - Composition for preventing and treating diabetes and diabetes complications comprising amphicarpaea edgeworthii var. trisperma powder or an extract thereof - Google Patents

Abstract

The present invention relates to a method for producing a sweet potato ( Amphicarpaea) having a hypoglycemic effect edgeworthii there is . trisperma powder or an extract thereof. The present invention relates to a composition for prevention and treatment of diabetes, and a composition for preventing and treating diabetes and a composition for preventing and treating diabetes by suppressing and controlling the rapid increase of blood glucose concentration And can be usefully used for functional foods.

Description

TECHNICAL FIELD The present invention relates to a composition for prevention and treatment of diabetes and diabetic complications including peanut powder or extract thereof. TRISPERMA POWDER OR AN EXTRACT THEREOF}

The present invention relates to a method for producing a sweet potato ( Amphicarpaea) having a hypoglycemic effect edgeworthii there is . trisperma ) powder or an extract thereof as an active ingredient for the prevention and treatment of diabetes and diabetic complications.

Diabetes mellitus is a disease in which insulin secretion is reduced or insulin function is lowered, and cells in the body can not utilize sugar, resulting in hyperglycemia. In the case of diabetes, hormone imbalance, including insulin, is characteristic of hyperglycemia due to abnormal regulation of physiological metabolism such as carbohydrate, protein, lipid and electrolyte metabolism. If such hyperglycemia persists, blood circulation disorder, retinal damage, Resulting in lower renal function and vascular complications, leading to serious chronic complications.

In particular, the incidence of cardiovascular diseases such as arteriosclerosis, cerebral infarction, cerebral thrombosis, and myocardial infarction is higher in diabetic patients than in normal subjects (Fuller, J.H., Lancet, 1, pp1373-1376, 1980). In diabetic patients, the risk of death from coronary artery disease or cerebrovascular disease is high, which is often caused by hypertension, hyperlipidemia, and obesity (Jung, Hapbaum, Korea Nutrition Society, pp15-18, 1984). 67% of type 2 diabetes patients were reported to have one or more lipid metabolism abnormalities (Harris, M.I. Diabetes Care, 23, pp754-758, 2000). In patients with type 2 diabetes, lipid metabolism abnormality occurs in which triglyceride and cholesterol levels increase and HDL-cholesterol declines (Goldberg, RB Diabetes Care, 4, pp561-572, 1981), which suggests that diabetic complications such as coronary artery disease (Reaven, JW Am. J. Med., 83, pp 31-40, 1987).

Diabetes is defined as a metabolic disorder caused by insulin secretion and insufficient secretion from the pancreas cells. It is accompanied by overproduction of glucose, body fat breakdown, protein waste, abnormal hyperglycemia of glucagon, (Abrams, JJ, Ginsberg, H, et al., Diabetes, 31, pp 903-910, 1982).

Diabetes mellitus is characterized by two types: Type 1 diabetes mellitus, which is caused by a deficiency of the insulin secretion hormone in the blood, It is also called juvenile diabetes because it occurs in a young age group. Type 2 diabetes mellitus occurs mainly after the age of 40, and it accounts for most of the diabetic patients in Korea. Unlike type 1, it is called adult type diabetes. The cause of the disease is not clear yet, but it is known that genetic factors and environmental factors are involved together. As a cause of type 2 diabetes, insulin secretion in pancreatic beta cells and insulin action defects in target cells (insulin resistance) are all observed.

The most important goal in the treatment of diabetes is to regulate blood glucose levels as close to normal as possible. Regulation of postprandial blood glucose with fasting blood glucose is important in the improvement of diabetic symptoms and prevention and treatment of complications. Drug therapy, There is exercise therapy.

Alpha-glucosidase inhibitors, sulfonylurea preparations and biguanide preparations are currently used for oral hypoglycemic agents used in patients with type 1 and type 2 diabetes. Alpha-glucosidase inhibitors, Shodase inhibitors have a therapeutic effect of diabetes by reducing the postprandial blood glucose and blood insulin elevation by delaying the digestion and absorption of carbohydrates in the ingested diets. Alpha-glucosidase inhibitors promote the secretion in the small intestine of glucagon-like peptide-1, which does not cause hyperinsulinemia or hypoglycemia, promotes insulin secretion and inhibits glucagon secretion (Mooradian, AD, Thurman, JE et al., Drugs, 57, pp19-29, 1999; Baron, AD et al., Diabetes Research and Clinical Practice, 40, ppS54-S55, 1998).

Acarbose, Voglibose and Miglitol are currently used in clinical practice. However, in case of long-term use of alpha-glycosidase inhibitor, abdominal bloating, vomiting, diarrhea (Hanefeld, M. et al., Journal of Diabetes and its Complications, 12, pp228-237, 1998).

Seaweed ( Amphicarpaea edgeworthii there is . trisperma ) is a perennial herbaceous plant belonging to the family Zingiberaceae, which is 1 to 2 m long and has spreading hairs all downward. In Korea, it is a common species in mountain paddy fields around the country. It is distributed in China, Japan, and India. The soymilk is " Amphicarpaea bracteata subsp.edgeworthii (Benth.) H. Ohashi "," Amphicarpaea edgeworthii there is . japonica ", etc. Leaves are alternate phyllotaxis, long petiole, 3 lobes are ovate, flowers bloom in June-September, purple, flowers are mature from August, fruits are cones, flat oval, Figure 10 is a photograph of the seeds distributed in Korea, showing leaves and flowers, and Figure 11 is a photograph of the seeds. In the oriental medicine, roots are used as a medicinal herb, It has been known to be effective in the treatment of limb pain. Its ingredients are essential oils of the seeds and its main constituents are Borneol, Bornyl-acetate, Linalool, Nerolidol ), Etc. (Lee, Chungseup et al., Literature Review on the Origin and Form of Signs, Journal of Korean Herbal Medicine, p96-105, 1986). However, none of the above documents have any effect on the diabetic and diabetic complications Not the time or the teachings bars.

[references]

[Document 1] Fuller, J. H., Lancet, 1, pp. 1373-1376, 1980

[Reference 2] Korean Nutrition Society. Abstracts of Publications. pp15-18, 1984

[Document 3] Harris, M.I. Diabetes Care, 23, pp 754-758, 2000

[Literature 4] Goldberg, R.B. Diabetes Care, 4, pp 561-572, 1981

[Literature 5] Reaven, J.W. Am. J. Med., 83, pp 31-40, 1987

[Literature 6] Abrams, J.J., Ginsberg, H, et al., Diabetes, 31, pp903-910, 1982

[Literature 7] Mooradian, A.D., Thurman, J.E. et al., Drugs, 57, pp19-29, 1999;

[Document 8] Baron, A.D. et al., Diabetes Research and Clinical Practice, 40, ppS54-S55, 1998

[Literature 9] Hanefeld, M. et al., Journal of Diabetes and its Complications, 12, pp228-237, 1998

[Literature 10] Lee, Chungseup et al., Korean Journal of Soil Science, p96-105, 1986

[Document 11] Am. J. Endocrinol. Metab. 288: E510-E518 (2005)

[Document 12]; Diabetologia 49: 1647-1655 (2006)

[Literature 13] J. Ethnopharmacol. 103: 491-495 (2006)

[Literature 14] J. Med. Chem. 43: 3487-3494 (2003)

[Literature 15] Metabolism 50: 1049-1053 (2001)

[Literature 16] Metabolism 53: 488-499 (2004)

The present invention is to provide a novel substance which is free from adverse effects on the living body and excellent in postprandial blood glucose suppressing action. For this purpose, the pharmacological effects of the extract of Seaweed Powder or its extract were investigated by the blood glucose measurement experiment using the db / db mouse model, the triglyceride, total cholesterol, blood BUN, ALT and AST in the serum As a result, it has been confirmed that there is an excellent therapeutic effect on diabetes, improvement of lipid metabolism and complications due to diabetes, thereby completing the present invention.

It is an object of the present invention to provide a pharmaceutical composition for the prevention and treatment of diabetes or diabetic complication which contains an effective ingredient of a soya bean powder or an extract thereof having an excellent blood glucose lowering effect.

It is also an object of the present invention to provide a health functional food for preventing or ameliorating diabetes or diabetic complication, which contains an effective ingredient of soya bean powder or its extract having an excellent blood glucose lowering effect.

In the present invention,

Seaweed ( Amphicarpaea edgeworthii there is . trisperma ) powder or an extract thereof as an active ingredient for the prevention and treatment of diabetes or diabetic complications. The extract can be extracted with water, an organic solvent or a mixed solvent thereof. Such diabetic complications include arteriosclerosis, cerebral infarction, cerebral thrombosis, myocardial infarction, hypertension, hyperlipidemia, obesity, and the like.

In the present invention,

Seaweed ( Amphicarpaea edgeworthii there is . trisperma ) powder or an extract thereof as an active ingredient for preventing or ameliorating diabetes or diabetic complications. The health functional food of the present invention may have any one of tablet, capsule, powder, granule, liquid, and ring.

In the present invention,

Amphicarpaea, which shows the effects of improving blood sugar, improving lipid metabolism and preventing and treating diabetic complications edgeworthii there is . trisperma ) powder or an extract thereof. Such foods include foods, beverages, gums, tea, vitamin complexes, or health functional foods.

As described above, in the present invention, blood glucose measurements, serum triglyceride, total cholesterol, blood BUN, ALT, and AST measurement tests on the soybean powder or its extract, It was confirmed that excellent therapeutic effect and excellent blood glucose lowering effect were found in the improvement of metabolism and complications due to diabetes. The composition of the present invention comprising the soybean powder or extract thereof as an active ingredient can be usefully used as a pharmaceutical composition and a health functional food for the prevention and treatment of diabetes or diabetic complications.

Brief Description of the Drawings Fig. 1 is a graph showing the effect of diabetic rats (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice; 6 weeks) treated with barnabas extract, ABSE and B-ABSE (Figures are expressed as mean ± SEM, and values with different indications differ from each other at specific time points. Statistically statistically significant compared to negative control by T test * p < 0.05, *** p < 0.001)).
FIG. 2 is a graph showing blood glucose levels in BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice (n = 9) treated with barnabas extract, ABSE and B-ABSE (Figures are expressed as mean ± SEM, and values with different indications differ from each other at specific time points. Statistically statistically significant compared to negative control by T test * p < 0.01)).
Figure 3 is a graph showing blood neutrophil counts (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice; 9 weeks) in rats (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice) treated with barnabas extract, ABSE and B- (The values are expressed as mean ± SEM, and the values having different indications are different from each other at specific time points.) Statistically, by comparing with the negative control by statistical test, (* P < 0.01).
FIG. 4 is a graph showing blood blood levels in blood (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice; 9 weeks) in rats (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice) treated with barnabas extract, ABSE and B- urea nitrogen level (the values are expressed as mean ± SEM, and the values with different indications differ from each other at specific time points). Statistically, by T test, statistically significant (* P < 0.01)).
FIG. 5 is a graph showing the results of blood total counts (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice; 9 weeks) in rats (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice) treated with barnabas extract, ABSE and B- Cholesterol levels (values are expressed as mean ± SEM, and values with different indications differ from each other at specific time points, statistically statistically significant compared to negative control by the T test method (* p &lt;0.01));
FIG. 6 is a graph showing blood AST (blood glucose level) in mice (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice; 9 weeks) induced with diabetic rats treated with barnabas extract, ABSE and B-ABSE And ALT levels (the values are expressed as mean ± SEM and the values with different indications differ from each other at specific time points), statistically compared with the negative control by the T test method (* P <0.01).
FIG. 7 shows the effect of AST and ALT levels in blood on db / db mice (Makoto T. et al., Pulmonary exposure to diesel exhaust particles enhancing fatty changes of the liver in obese diabetic mice. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 19: 17-22, 2007).
Figure 8 shows the mean body weight (BKS) of the diabetic rats (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice; 9 weeks) treated or not treated with banaba extract, ABSE and B- ABSE Fig.
Figure 9 shows the dietary intake of diabetic rats (BKS.Cg-m ^{+ / +} Lepr ^{db / J} diabetic mice; 9 weeks) treated or not treated with barnabus extract, ABSE and B-ABSE Respectively.
Fig. 10 is a photograph of a seedling growing wild in Korea.
Fig. 11 is a photograph of a seed of a soybean sprout native to Korea.

The compositions of the present invention saekong (Amphicarpaea edgeworthii there is . trisperma ) powder or an extract thereof as an active ingredient.

The soymilk as defined in the present invention has a scientific name of " Amphicarpaea edgeworthii there is . trisperma & quot ;, or " Amphicarpaea bracteata subsp.edgeworthii (Benth.) H. Ohashi "or" Amphicarpaea edgeworthii there is . quot; japonica. " The soybean is a cone, flat oval, and has hairs along the circumference, and contains three seeds. In the present invention, " soybean seeds " it means.

The safflower powder includes all of the dried or powdered powder of the safflower seed. The extract is water, an organic solvent or a mixed solvent extract thereof of the soya powder. More preferably, the extract is an extract obtained by extracting with water, an organic solvent or a mixed solvent thereof. Such diabetic complications include arteriosclerosis, cerebral infarction, cerebral thrombosis, myocardial infarction, hypertension, hyperlipidemia, obesity and the like, in particular hypertension, hyperlipidemia or obesity.

The soybean powder and the extract thereof of the present invention will be described in detail.

The commercially available dry soya bean can be ground with a grinder to obtain the soya bean powder of the present invention in a dry state. Also, the soya bean powder may be grown at 20 to 120 ° C for about 1 to 72 hours, and then dried according to a conventional drying method in the art to obtain the bean sprouts of the present invention in the form of a thickened powder. In addition, after the bean curd powder or the dried bean curd dried powder is freeze-dried to a size of about 2 to 15 times, preferably about 5 to 10 times the weight of the sample, water or an organic solvent such as methanol, ethanol, a C ₁ to C ₄ lower alcohol, a polar solvent of, or extracts of the present invention by extraction with a mixed solvent such as butanol can be obtained. Extraction can be carried out by using hot water extraction, cold extraction, reflux cooling extraction, ultrasonic extraction, or the like, preferably at 20 to 120 ° C for about 1 to 72 hours with water. Preferably, the extraction method is followed by filtration under reduced pressure and concentration The extract of the present invention can be obtained.

In addition, conventional fractionation processes can also be performed (Harborne, J. B. Phytochemical methods: A guide to modern techniques of plant analysis, 3rd ed., Pp6-7, 1998).

In the present invention, the present invention provides a method of measuring the blood glucose level, triglyceride, total cholesterol, blood BUN, ALT and AST in the serum of a subject using the db / db mouse model, The therapeutic effect was confirmed. As a result, it was confirmed that there was excellent therapeutic effect and excellent blood glucose lowering effect on diabetes, improvement of lipid metabolism and complications due to diabetes.

Also, the soybean extract has been used for a long time as an edible or herb medicine, and the extracts of the present invention have no toxicity and side effects.

The pharmaceutical composition for preventing or treating diabetes or diabetic complications containing the extract of Seaweed of the present invention contains the above extract in an amount of 0.1 to 50% by weight based on the total weight of the composition.

The pharmaceutical compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The pharmaceutical dosage forms of the extract of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in suitable aggregates.

The pharmaceutical composition containing the extract according to the present invention can be administered orally in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized injection solutions And can be used as formulations. Examples of carriers, excipients and diluents that can be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, the preparation is carried out using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, Sucrose), lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of liquid formulations for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Witepsol, macrogol, Tween 61, cacao paper, laurin, glycerogelatin and the like may be used as a base for suppositories.

The preferred dosage of the extract of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the administration route and the period of time, but can 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 10000 mg / kg per day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

The extract of the present invention can be administered to mammals such as rats, mice, livestock, humans and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injection.

The definitions of the above excipients, binders, disintegrants, lubricants, mating agents, flavoring agents and the like of the present invention can be found in the literature (Korean Pharmacopoeia, Korean Pharmacopoeia, Korean Society of Pharmacy, 5th edition, p33-48 , &Lt; / RTI &gt; 1989), and includes functions, actions, and the like that are the same or similar.

In addition, the present invention relates to a method for producing a sweet potato having a hypoglycemic effect, bracteata The present invention provides a health functional food for prevention and treatment of diabetes or diabetic complications containing as an active ingredient a subsp.edgeworthii (Benth.) H. Ohashi powder or an extract thereof.

The term " health functional food " as defined in the present invention means a food prepared and processed by using raw materials or ingredients having useful functions in the human body, and substantially refers to a health functional food according to &quot; &Lt; / RTI &gt; In the present invention, the term " functional &quot; means that the structure and function of the human body are ingested for the purpose of obtaining a beneficial effect for health use such as control of nutrients or physiological action. The health functional food for the prevention of diabetes according to the present invention contains 0.01 to 95% by weight, preferably 1 to 80% by weight of the extract, based on the total weight of the composition. In addition, for the purpose of preventing diabetes, it is possible to manufacture and process health functional foods in the form of tablets, capsules, powders, granules, liquids, and circles.

In addition, the present invention provides a health supplement supplemented with a food or beverage for the purpose of improving blood sugar, improving lipid metabolism and preventing and treating diabetic complications. Foods to which the soybean meal powder or extract can be added include, for example, various foods, beverages, gums, tea, vitamin complexes, and health functional foods. At this time, the amount of the extract in the food or drink may be 0.01 to 100% by weight of the total food, and the health beverage composition may be added in an amount of 0.02 to 50 g based on 100 ml.

The health functional beverage composition of the present invention is not particularly limited to the other components except that the above-mentioned extract is contained in an indicated ratio as an essential ingredient, and various flavors or natural carbohydrates such as ordinary beverages are added as an additional ingredient can do. 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 polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above, the extract of the present invention can also be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and aging agents (cheese, chocolate, etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the samples of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the inventive sample.

Hereinafter, the present invention will be described in detail with reference to the following Examples, Reference Examples and Experimental Examples. However, the following examples, reference examples and experimental examples are illustrative of the present invention, and the contents of the present invention are not limited by the following examples, reference examples and experimental examples.

Example  One. Soybean  Preparation of powders and extracts

1-1. Soybean  Powder and potato powder

Amphicarpaea of the present invention bracteata subsp.edgeworthii (Benth.) seed was used as pulverized and dried from Gyeongbuk Mungyeong woojidong mixer (hereinafter, "ABSE" La), ABSE the seed saekong 250 ml of water was added to 500 g of the dried product, and the mixture was boiled at 95-100 ° C for 5 minutes, and then pulverized with a mixer to obtain 720 g of a powder (hereinafter referred to as " B- ABSE ").

1-2. Soybean  Powder and boiled powder extract

150 g of the gray seed powder obtained in the above 1-1 and 150 mg of the gray seed powder obtained in the above step were extracted with 13 L of 70% methanol for 24 hours at 40 ° C, and then filtered under reduced pressure through a filter paper (Wattsman, USA) (Hereinafter abbreviated as " ABSE1 &quot;) and an increased amount of shark gray powdery extract (hereinafter referred to as " B- ABSE1 &quot;) were obtained by concentrating under reduced pressure at 37 DEG C with a concentrating machine , And stored at 20 ° C.

Reference example  1. Preparation of Type 2 diabetic animal models and samples

1-1. Test substance

Samples of the above example were administered orally (twice daily, 10:00 am, 6:00 pm) by diluting (suspending) the sample with physiological saline.

1-2. Positive control substance

As a positive control Barnabas extract (Banaba leaf extract, place of purchase: Wellness Barnabas ㈜, Appearance: brown tablet) was diluted with physiological saline after made into a powder (suspension) was orally administered once twice (10 a.m. and 6 p.m.) .

1-3. Antidiabetic agent  Evaluation of administration efficacy Preliminary animal test data base

Seven rats were divided into three groups of 6-week-old male db / db mice (26 g, Taconic Farms, Inc.) for each anti-diabetic agent group, and then the mice were divided into three groups at a temperature of 22 ± 2 ° C, a humidity of 55 ± 10% The body weight and blood sugar were measured at 0, 3, 6, 9, 12, and 15 days after the administration of the sample while maintaining the SPF (specific pathogen free) Concentration was selected.

1-4. Antimutant Diabetic  Evaluation of administration efficacy Animal experiment and sample collection

A 6-week-old male db / db mouse with obesity and diabetic symptoms showed artificial genetic mutation to block the feedback signal of leptin and to induce type 2 diabetes with overweight In this mouse model, the drug was administered orally and the same amount of physiological saline was administered to the control group. Seven mice per group were randomly assigned to the experimental group, db / db mice, divided into four groups, one group was saline, the positive control group was banaba leaf extract (100 mg / kg) Samples ABSE 2 g / kg and B- ABSE 2 g / kg were orally administered at 10:00 am and 18:00 pm, respectively, in 0.4 ml each. The rearing conditions of each group were maintained at SPF environment controlled by shading at a temperature of 22 ± 2 ° C., humidity of 55 ± 10% and a 12 hour interval in the same manner as in the preliminary animal experiment. On the 0, 7, 14 and 21 days, The changes were measured using a portable blood glucose meter (OneTouch ^™ , Johnson & Johnson, USA).

1-5. Blood analysis Autopsy and pathology analysis

As described above, three samples were administered to db / db mice for 15 days. Blood was collected from the animals of each group and centrifuged at 3,000 rpm for 10 minutes. The supernatant plasma was separated and insulin, AST, ALT, The blood biochemical markers related to blood lipid and other organ toxicities were analyzed by statistical methods such as total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN) (Student t-test).

In addition, liver, kidney, heart, pancreas, and lungs are excised and stored in 10% neutral buffered formalin and part of organs are stored in RNASol ^B to perform histopathological observations on major organs.

1-6. Statistical processing

Results from various experiments were recorded as mean ± standard error, and significance was determined using Student's T-test.

Experimental Example  1. Type 2 diabetic animal model BKS . Cg -m ^{+ / +} Lepr ^{db / J} In mice Anti-diabetic  effect

In order to confirm the hypoglycemic effect of the samples of the above-mentioned examples, an experiment was conducted by modifying the method disclosed in the literature [Am J Physiol Endocrinol Metab. 288: E510-E518 (2005); Diabetologia 49: 1647-1655 (2006); J. Ethnopharmacol. 103: 491-495 (2006); J. Med. Chem. 43: 3487-3494 (2003); Metabolism 50: 1049-1053 (2001); Nutrition & Metabolism 53: 488-499 (2004)].

1-1. Effect on blood sugar change

A 6-week-old db / db mouse model was orally administered with 100 mg / kg of positive control barnabas extract, 2 g / kg of ABSE in the experimental group, and 2 g / kg of B-ABSE in the morning and afternoon for 2 weeks. Blood was collected from the tail of a mouse with a portable blood glucose meter once a week and blood glucose was measured. On the day before the measurement, all mice were dieting (about 12 hours).

As shown in FIG. 1, the blood glucose level of the control group (NC) was increased from 342.1 mg / dL at 6 weeks to 582.1 mg / dL at 9 weeks of age, which was more than 70% ABSE showed the most inhibition of blood glucose change from 6 weeks to 9 wks. At 9 weeks of age, the ABSE group showed a 37.9% decrease in blood glucose compared with NC at 360.5 mg / kg (p <0.001). The positive control group, Barnabas extract and B-ABSE, showed similar blood glucose reductions as 26.2% and 26.4%, respectively (p <0.001).

At 6-week-old db / db mice, 100 mg / kg of positive control barnabas extract, 2 g / kg of ABSE in the experimental group and 2 g / kg of B-ABSE were orally administered in the morning and afternoon for 3 weeks. As a result, as shown in FIG. 1, the blood glucose level of the control group (NC) was increased from 342.1 mg / dL at 6 weeks to 582.1 mg / dL at 9 weeks of age. ABSE showed the most inhibition of blood glucose change from 6 weeks to 9 wks. At 9 weeks of age, the ABSE group showed a 37.9% decrease in blood glucose compared with NC at 360.5 mg / kg (p <0.001). After the end of the experiment, the blood was collected from the fasting state (about 12 hours) by removing the diet on the previous day, and the serum was separated. The serum glucose level was changed to 641 mg / dL And 427.0 mg / dL, respectively, in the ABSE group compared to the NC group (p <0.01).

These results are in close agreement with the result of blood glucose change in the tail vein shown in FIG. 1, and the blood glucose lowering effect of ABSE can be confirmed.

1-2. In serum  glucose( glucose ) Change measurement

At 9 weeks of age, diets were removed on the day before the experiment and the animals were anesthetized with ethyl ether in fasting state (about 12 hours). Blood was collected from the heart using a 3 ml syringe, left at room temperature for 1 hour, and centrifuged at 3000 rpm for 10 minutes The serum was separated and glucose change in the serum was measured with a serum automatic meter. The results are shown in FIG. The glucose level of NC was 641 mg / dL and that of ABSE group was 427.0 mg / dL, which was 33.4% lower than that of NC group (p <0.01).

* As a result of this experiment, the anti-diabetic effect of ABSE was observed as a result almost coinciding with the blood glucose change result in the tail vein in FIG. And the positive control banaba extract was 463 mg / dL, which showed a statistically significant decrease of 27.7% compared to the NC group (p <0.01). However, there was no statistical significance in the B-ABSE group (551 mg / dL), which was slightly lower than the NC group (14%).

Experimental Example  2. Type 2 diabetic animal model BKS . Cg -m ^{+ / +} Lepr ^{db / J} In mice  Effects on lipid metabolism and diabetic complications

In order to confirm the lipid metabolism and diabetic complication effects of the samples of the above-mentioned examples, an experiment was conducted by modifying the method described in the literature [Am J Physiol Endocrinol Metab. 288: E510-E518 (2005); Diabetologia 49: 1647-1655 (2006); J. Ethnopharmacol. 103: 491-495 (2006); J. Med. Chem. 43: 3487-3494 (2003); Metabolism 50: 1049-1053 (2001); Nutrition & Metabolism 53: 488-499 (2004)].

2-1. In serum  Triglycerides triglyceride , TG ) Change measurement

At 9 weeks of age, diets were removed on the day before the experiment and the animals were anesthetized with ethyl ether in fasting state (about 12 hours). Blood was collected from the heart using a 3 ml syringe, left at room temperature for 1 hour, and centrifuged at 3000 rpm for 10 minutes Serum was separated and serum triglyceride (TG) change was measured with a serum automatic meter. The results are shown in FIG.

This experimental result is shown in Fig. 3 NC of triglyceride (TG) level was 67.0 mg / dL been high, natural group of ABSE group is 37.0 mg / in dL least 44.7% compared with the NC group statistically significant decrease in (P < 0.001). These results were almost identical with those of the glucose - suppressing effect in serum, and the blood - improving effect of ABSE could be observed. And 50.3 mg / dL of the banaba extract, which is a positive control, showed a statistically significant decrease of 25.3% (p <0.01) compared to the NC group. However, the B-ABSE group was 55.0 mg / dL, which was slightly decreased to 17.9% as compared with the NC group.

2-2. In serum blood urea nitrogen  ( BUN ) Change measurement

At 9 weeks of age, diets were removed on the day before the experiment and the animals were anesthetized with ethyl ether in fasting state (about 12 hours). Blood was collected from the heart using a 3 ml syringe, left at room temperature for 1 hour, and centrifuged at 3000 rpm for 10 minutes The serum was separated and the BUN change in the serum was measured with a serum automatic meter. The results are shown in FIG.

As shown in FIG. 4, the BUN level of NC was 27.1 mg / dL in the NC group, and 29.4 mg / dL B-ABSE group in the ABSE group showed no difference compared to the 29.8 mg / The extract of banaba extract showed a statistically significant increase of 32.0% (36.0 mg / dL) compared to the NC group (p <0.05).

2-3. In serum  Total cholesterol ( total cholesterol ) Change measurement

At 9 weeks of age, the animals were anesthetized with ethyl ether in the fasting state (about 12 hours), and the blood was collected from the heart using a 3 ml syringe. The animals were left at room temperature for 1 hour and centrifuged at 3000 rpm for 10 minutes The serum was separated and the total cholesterol level in the serum was measured with a serum automatic meter. The results are shown in FIG.

As shown in FIG. 5, the total cholesterol level of NC was 142.0 mg / dL in the NC group, 150.0 mg / dL in the barnaby extract group, 151.0 mg / dL in the ABSE group and 151.0 mg / dL, respectively.

2-4. In serum ALT Wow AST  Change measurement

At 9 weeks of age, diets were removed on the day before the experiment and the animals were anesthetized with ethyl ether in fasting state (about 12 hours). Blood was collected from the heart using a 3 ml syringe, left at room temperature for 1 hour, and centrifuged at 3000 rpm for 10 minutes Serum was separated and serum ALT and AST levels were measured with a serum automatic meter. The results are shown in FIG.

As shown in FIG. 6, the ALT level was 78.0 U / L in the NC group, and 65.5 U / L in the barnaby extract group, 100.0 U / L in the ABSE group and 108.8 U / L and the positive control group, Barnabas extract, showed liver function improving effect compared with NC. The AST level was 189.4 U / L in the NC group, and 90.1 U / L in the banaba extract group, 171.9 U / L in the ABSE group and 193.9 U / L in the B-ABSE group, The number of mice was decreased by 51.9% compared with that of NC. However, there was no difference between the experimental group ABSE and the B-ABSE group. And the db / db mouse model is an obesity / type 2 diabetic model, which is why AST levels are placed relative to normal mice (Fig. 7).

Experimental Example  3. Effects on body weight and dietary changes

Six week old db / db mice were divided into seven groups, and their body weight changes were measured twice a week. Dietary intake was measured at 3-day intervals, and the average daily dietary intake was observed in each experimental group (7 mice). The results are shown in FIGS. 8 and 9.

As shown in FIGS. 8 and 9, weight change did not significantly change in NC, Barnabas extract, ABSE, and B-ABSE groups. However, the amount of dietary intake per day increased significantly after 7 weeks of age, and the dietary intake of ABSE and B-ABSE increased 26.7% and 10.7%, respectively, after 8 weeks of age. However, the body weight of the ABSE and B-ABSE groups did not show a proportional increase compared with the increase of the dietary intake.

In the diabetic model db / db mice, the levels of blood sugar and triglyceride were significantly decreased (p <0.01, p <0.001) compared to the untreated group in the ABSE group and the B-ABSE group. In addition, the dietary intake was higher in the soybean powder (ABSE) group and the boiled soybean (B-ABSE) group than in the non-treated group, and no change in body weight was observed and no gross abnormality was observed. Particularly, the group administered with soybean powder (ABSE) showed a blood glucose lowering effect that relieves fasting hyperglycemia after fasting

Experimental Example  4. Acute Toxicity Experiment

Specific pathogen-free (SPF) SD rats at 6 weeks of age were used for acute toxicity tests. Two animals per group were orally administered the extract of the present invention with a dose of 100 mg / kg once. After the administration of the test substance, the mortality, clinical symptoms and weight changes of the animals were observed, hematologic test and blood biochemical test were performed, and autopsy was performed to observe whether or not the organs and thoracic organs were abnormal.

As a result of this experiment, there were no clinically symptomatic or dead animals in all animals treated with the test substance, and no toxic change was observed in weight change, blood test, blood biochemical test and autopsy. Above results, the extract of the present invention did not show any toxicity changes even 100 ㎎ / ㎏, respectively in rats, oral administration of a minimum lethal dose (LD ₅₀₎ was determined to be a safe substance than 100 ㎎ / ㎏.

A preparation example of a pharmaceutical composition containing the extract of the present invention will be described below. These formulation examples are not intended to limit the invention, but merely to illustrate it.

Formulation example  One. Sanje  Produce

ABSE1 extract 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  2. Preparation of tablets

ABSE1 extract 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  3. Preparation of capsules

ABSE1 extract 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

ABSE1 extract 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO _{4 12} H ₂ O 26 mg

(2 ml) per ampoule in accordance with the usual injection method.

Formulation example  5. Liquid  Produce

ABSE extract 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added to purified water in accordance with the usual preparation method of the liquid preparation and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto to adjust the total volume to 100 ml. The mixture was filled in a brown bottle and sterilized to prepare a liquid preparation do.

Claims (7)

Seaweed ( Amphicarpaea edgeworthii there is . trisperma ) powder or an extract thereof as an active ingredient for the prevention and treatment of diabetes or diabetic complications. The pharmaceutical composition according to claim 1, wherein the extract is extracted with water, an organic solvent or a mixed solvent thereof. The pharmaceutical composition according to claim 1, wherein the diabetic complication is arteriosclerosis, cerebral infarction, cerebral thrombosis, myocardial infarction, hypertension, hyperlipidemia, or obesity. Seaweed ( Amphicarpaea edgeworthii there is . trisperma ) powder or an extract thereof as an active ingredient for preventing or ameliorating diabetes or diabetic complications. The health functional food according to claim 4, wherein the health functional food has one of tablet, capsule, powder, granule, liquid, and ring. ( Amphicarpaea edgeworthii var. Trisperma ) powder or an extract thereof, which shows improvement of blood sugar, improvement of lipid metabolism, prevention and improvement of diabetic complication. [Claim 7] The health supplement according to claim 6, wherein the health supplement is in the form of a food, beverage, gum, tea or vitamin complex.

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