KR20110100880A - Composition comprising quercetin for lowering blood glucose - Google Patents

Abstract

The present invention relates to a composition for lowering blood sugar containing quercetin as an active ingredient, and more particularly, the present invention relates to a composition for lowering blood glucose, including a composition for quercetin as an active ingredient, a composition for preventing or treating diabetes or diabetic complications, and diabetes or diabetes The present invention relates to a dietary supplement showing the effect of preventing and improving complications. The quercetin compound according to the present invention has an effect of reducing blood sugar after meals and fasting when administered to an animal model inducing diabetes, and has an effect of reducing the concentration of glycated hemoglobin in the blood as well as inhibiting weight gain. Since it is effective, it can be used as a pharmaceutical use to prevent and treat diabetes or diabetes complications caused by hyperglycemia, and can also be used as a food use to improve diabetes or diabetes complications.

Description

Composition for quercetin for lowering blood glucose containing quercetin as an active ingredient

The present invention relates to a composition for lowering blood sugar containing quercetin as an active ingredient, a composition for preventing or treating diabetes or diabetic complications, and a health functional food showing an effect of preventing and improving diabetes or diabetic complications.

The mortality rate of diabetes among Koreans increased from 11.8 per 100,000 population in 1990 to 22.6 in 2000, increasing 91.5% over the last decade. Diabetes is ranked fourth (Korea National Statistical Office.Annual) Report on the Cause of Death Statistics 19. 1999; Korea National Statistical Office. Annual Report on the Cause of Death Statistics 21. 2002).

In general, diabetes mellitus (Diabetes mellitus) is defined as a series of metabolic disorders characterized by hyperglycemia, and is known as a disease caused by abnormally high glucose levels in humans and mammals. In addition, these abnormal glucose levels raise the level of hemoglobiin in plasma, chronic hyperglycemia, atherosclerosis, micro angiopathy, kidney disease, heart disease, diabetic retinopathy. It causes a series of complications such as diabetic retinopathy and cataracts.

In addition, such diabetes is classified into two types, namely type 1 diabetes and type 2 diabetes, and type 1 diabetes progresses to extreme hyperglycemia due to reduced insulin production due to pancreatic beta cell damage and dysfunction. And often indicate ketoosis or ketoacidosis. Type 2 diabetes is known to be caused by insulin resistance, which results in impaired insulin secretion, increased endogenous glucose production in the liver, and decreased glucose availability in peripheral insulin-sensitive tissues. Although it progresses, there are not as many cases of ketoosis or ketoacidosis as those of type 1 diabetes.

On the other hand, the most widely used diagnostic method for diagnosing and treating such diabetes is a method of examining the blood glucose level in fasting blood. However, the fasting blood sugar control is important when investigating the long-term glycemic control of diabetic patients. It is also important to measure glycated protein and postprandial hyperglycemia. This is because this value greatly affects the development and progression of complications. In particular, postprandial hyperglycemia decreases insulin sensitivity (Koivisto VA, Diabetes Care , 16, pp29-39, 1993) decreases pancreatic function and reduces insulin secretion (Baron AD, Diabetes Research Clinical Practice , 40, ppS54-S55, 1998) have been reported to exacerbate the condition of diabetes mellitus and cause macrovascular and microvascular complications (Defronzo RA, Diabetologia, 21, pp165-171, 1981; Young IR, Stout RW , Diabetes Metabolism , 13, pp 301-306, 1987).

In addition, glycated hemoglobin has been used as an important glycemic control index as a measure of knowing the average blood glucose level in the recent 3 to 4 months in diabetics. Normally, red blood cells have an average lifespan of 120 days, and if hyperglycemia persists during this period, non-enzymatic and irreversible glycation of hemoglobin in red blood cells continues, leading to increased glycated hemoglobin levels in diabetes (Gabbay KH). , et al., The Journal of Clinical Endocrinology and Metabolism , 44, pp 859-864, 1977). Therefore, it has been reported that the measurement of glycated hemoglobin is more meaningful than the fasting blood sugar (Ahn, Hyun-Sook, Eun-Yeon Lim, Hae-ri Kim, Korean Journal of Food and Nutrition, 26, pp914-919, 1997; Gabbay KH, et al. ., The Journal of Clinical Endocrinology and Metabolism , 44, p859-864, 1977). Therefore, glycated hemoglobin reflects long-term glycemic control and is an important index indicating the degree of treatment of diabetes mellitus, so regular measurement and control of glycated hemoglobin is important in the prevention of diabetic complications.

Furthermore, currently used diabetes treatment includes drug therapy, diet and exercise therapy, and oral hypoglycemic agents used for drug therapy include sulfonylureas and repaglinide and biguanide depending on the mechanism of action of the drug. Biguanides, α-glucosidase inhibitors and thiazolidinediones.

Among these, sulfonate agents are mostly metabolized in the liver and excreted in the urine, which induces the depolarization of the pancreatic beta-cells and increases calcium influx in the cells, thereby increasing insulin secretion, but there are problems associated with cardiovascular side effects. In addition, biguanide is a drug that inhibits hepatic glucose production by inhibiting glucose production and glucogen breakdown in the liver and increases the sensitivity to insulin in the muscles of the liver and peripheral tissues, but also involve digestive side effects including abdominal bloating and diarrhea. In addition, it is prohibited to use in patients with kidney disease, liver disease, respiratory failure, hypoxemia, and infectious diseases. In addition, thiazolidinediones were oral hypoglycemic agents that increase insulin sensitivity, but were banned in the United States in March 2000 due to serious liver toxicity.

Alphaglucosidase inhibitors, on the other hand, reduce the rate of degradation of small and disaccharides in food, resulting in a rapid rise in post-prandial blood sugar and consequently reduced insulin response in the blood (Lembcke et al., Digestion. 31, 120-127 (1985). Bischoff, Chin Invest.Med. 18 (4): 303-311 (1995)). Among them, acarbose, which is a recently used alpha glucosidase inhibitor, is a drug made of a secondary metabolite obtained by culturing and cultivating radiation mycobacteria (Actinomycetales). Decreases the function of glucosidase (maltase, isomaltase, sucrase, glucoamylase, etc.) that degrades and delays hydrolysis of carbohydrates such as starch, thus preventing post-prandial blood sugar levels (Breitmeier et al., Arch. Bilchem) Biophys. 346: 7-14 (1997). Acarbose has also been reported to slow glucose uptake to improve postprandial hyperglycemia and hyperinsulinemia, a problem in diabetics (Breitmeier et al., Arch. Bilchem. Biophys. 346: 7-14 ( 1997)). However, the existing alpha glucosidase inhibitors have the ability to inhibit amylase, which also inhibits the activity of amylase and thus does not easily degrade the starch, a polymer (Breitmeier et al., Arch. Bilchem. Biophys. 346: 7-14 (1997). )), Abdominal bloating, discomfort, diarrhea and other side effects are accompanied by a small dose slowly to increase the disadvantage. In addition, Voglibose (Odaka, H. et al., J. Jpn. Soc. Nutr. Food Sci. 45: 27 (1992)) has been released as a drug with a similar mechanism of action (Basen). Because of the large amount absorbed into the body during oral administration, there remains a risk of inhibiting glycogen metabolism and glycoprotein biosynthesis in the liver or muscle tissue (Kwon Young-in et al., Bioindustry. 11 (4): 49-53 (1998)).

Therefore, as described above, the conventionally used diabetes treatment has a problem in that side effects such as abdominal bloating and vomiting diarrhea occur in some patients when the treatment is taken for a long time (Hanefeld M., Journal of Diabetes and its Complications , 12, pp228-237, 1998), and furthermore, the development of new treatments for the effective treatment of diabetes is urgent as the specific mechanisms and mechanisms for the development of diabetes have not been identified.

Accordingly, the present inventors confirmed that the quercetin compound, which has been known to have an antioxidant effect, has an activity of regulating blood sugar and has an effect of reducing the concentration of glycated hemoglobin in the blood, thereby enabling the use of the quercetin compound as a therapeutic agent for diabetes. It was clarified.

Accordingly, an object of the present invention is to provide a composition for lowering blood glucose, which contains quercetin or a salt thereof as an active ingredient.

In addition, another object of the present invention to provide a composition for the prevention or treatment of diabetes mellitus or diabetic complications containing quercetin (Quercetin) or a salt thereof as an active ingredient.

It is another object of the present invention to provide a dietary supplement comprising quercetin and a food-acceptable food supplement additive which exhibits a prevention and improvement effect of diabetes or diabetic complications.

In order to achieve the above object of the present invention, the present invention provides a composition for lowering blood glucose, which contains quercetin or a salt thereof as an active ingredient.

In one embodiment of the invention, the quercetin may inhibit weight gain, reduce the concentration of glucose in the plasma or reduce the concentration of glycated hemoglobin in the blood.

The present invention also provides a composition for the prevention or treatment of diabetes mellitus or diabetic complications containing quercetin or a salt thereof as an active ingredient.

In one embodiment of the present invention, the diabetic complication may be selected from the group consisting of stroke, coronary heart disease, arteriosclerosis and myocardial infarction cardiovascular disease.

In one embodiment of the present invention, the diabetes may be type 2 diabetes.

Furthermore, the present invention provides a dietary supplement comprising quercetin and a foodstuff acceptable food supplement additive which exhibits a prevention and improvement effect of diabetes or diabetic complications.

The quercetin compound according to the present invention, when administered to an animal model inducing diabetes, has an effect of reducing blood glucose present in the blood at the time of meal and on an empty stomach, and in addition to reducing the concentration of glycated hemoglobin in the blood, Since it has an effect of suppressing the increase, it can be used as a pharmaceutical use that can prevent and treat diabetes or diabetes complications caused by hyperglycemia, and can also be used as a food use that can improve diabetes or diabetes complications.

1 is a graph showing a comparison of the glucose content in serum by taking blood from the tail vein at each time after the starch-only group and the starch and the quercetin of the present invention were administered to male rats. .
Figure 2 is a graph showing the comparison of the measurement of the amount of fasting blood glucose in the experimental group injected quercetin and the control group not injected quercetin in the animal model induced type 2 diabetes in one embodiment according to the present invention will be.
3 is a column chromatography of the glycated hemoglobin concentration in the experimental group injected with quercetin and a control group not injected with quercetin in the animal model induced by type 2 diabetes in one embodiment according to the present invention. The measurement is shown in the graph.

The present invention is characterized by providing a composition for lowering blood sugar, which contains quercetin or a salt thereof as an active ingredient.

Quercetin, also known as a natural antioxidant, is a kind of flavonoid belonging to polyphenols among natural antioxidants, and contains a large amount of about 30 to 500 mg / kg in plant, especially onion, asparagus, kale, apple, broccoli, grapes, and red wine. and is, as a 5,7,3 ', 4'-tetrahydroxy derivatives of the flavonols that formula is C ₁₅ H ₁₀ O _7, and the determination of the yellow, it is known that the melting point of 316~317 ℃.

In addition, quercetin has a very strong antioxidant activity, which is four times higher in antioxidant activity than catechin, a flavonoid having the same number of hydroxyl groups. Quercetin has a large resonance structure due to its chemical structure, antioxidant activity, vitamin P action, and ultraviolet absorption. It is one of the compounds that is expected to be applied to foods, medicines, cosmetics, etc. (Foti, M., Piattelli, M., and Ruberto, G. 1996. J. Agric.Food Chem . 44, 497-501). , Wang, H., Cao, G. and Prior, LP 1996. J. Agric.Food Chem. 44, 701-705). In addition, quercetin and other flavonoids, recently considered mutagen in the Ames test, have been reported to have anticarcinogenic activity that inhibits the development of tumor cells in some animal experiments (Alegria, BC 1992, Food Technol. 46, 65-68), in particular, have been shown to have activity to prevent cancer infiltration and metastasis (Marc, EB and Eric, AB 1994. Food Technol . 48, 121-124 ).

Accordingly, the present inventors have found that quercetin having various physiological activities can prevent or treat diabetes through an activity of regulating blood glucose.

In other words, according to one embodiment of the present invention, to investigate whether the quercetin is effective in lowering blood sugar, the male rats were reared in the group administered with quercetin and the control group not administered, and then the weight and postprandial blood sugar As a result of measuring the change, the quercetin-administered group showed no significant weight loss compared to the control group, but the blood glucose was significantly decreased (see FIG. 1).

In addition, according to another embodiment of the present invention, after administering quercetin in an animal model in which type 2 diabetes is induced, and measuring a change in weight and plasma glucose concentration, the experimental group administered quercetin, Compared with the control group not administered quercetin, the body weight of the diabetic animal model was significantly decreased, and the concentration of glucose in the fasting plasma was also significantly reduced (see Table 5 and FIG. 2).

Therefore, through the above results, the present inventors found that the quercetin of the present invention has an effect of effectively reducing fasting and postprandial blood sugar, and the fact that quercetin has a blood glucose lowering effect through the fact that it also has an activity of reducing weight in diabetic animal models. It was found that diabetes can be prevented and treated.

On the other hand, glycated hemoglobin in blood is used as a glycemic control indicator to know the average blood sugar level in diabetic patients, it is known that the level of glycated hemoglobin increases when diabetes occurs.

In order to more clearly identify the hypoglycemic effect of quercetin according to the present invention, the present inventors administered quercetin in a diabetic-induced animal model, and then measured the concentration of glycated hemoglobin in heal solution compared with a control group not administered quercetin. It was.

As a result, in the experimental group administered quercetin, the concentration of glycated hemoglobin in the blood was significantly reduced compared to the control group (see Fig. 3).

Thus, the inventors of the present invention was able to confirm that the quercetin of the present invention can prevent or treat diabetes and diabetic complications through the action of lowering blood glucose in blood and reducing the concentration of glycated hemoglobin.

Therefore, the present invention can provide a composition for lowering blood sugar, which contains quercetin or a salt thereof as an active ingredient.

In addition, the quercetin according to the present invention may be used in the form of a salt, preferably a pharmaceutically acceptable salt. The salt is preferably an acid addition salt formed by a pharmaceutically acceptable free acid, and an organic acid and an inorganic acid may be used as the free acid. The organic acid is not limited thereto, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, Glutamic acid and aspartic acid. In addition, the inorganic acid includes, but is not limited to, hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid.

Quercetin according to the present invention may be isolated from nature or prepared and used by chemical synthesis known in the art.

Preferably, the quercetin of the present invention may be obtained by extraction and separation from nature using a method of extracting and separating conventional materials.

In addition, a suitable solvent for extracting quercetin from the natural is not limited thereto, and water or an organic solvent may be used. Preferably, purified water, methanol, ethanol, propanol, isopropanol (isopropanol), butanol, acetone, ether, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane Various solvents, such as (cyclohexane), can be used individually or in mixture.

In addition, the separation and purification of quercetin from extracts extracted from nature is a method of separation and purification known in the art, such as column chromatography filled with various synthetic resins, such as silica gel or activated alumina. ) And high performance liquid chromatography (HPLC) may be used alone or in combination. However, the extraction and separation and purification method of the active ingredient is not necessarily limited to the above method.

In one embodiment of the present invention was used commercially purchased quercetin commercially available in the art.

On the other hand, when diagnosing diabetes, in general, diagnosing diabetes, usually with only fasting blood sugar, which is a common sense, in fact, it is desirable to diagnose diabetes if any of the following three items belong to Do. That is, (1) when fasting plasma glucose concentrations collected after fasting for 8 hours or more are 126 mg / dl or more, (2) serum glucose concentrations collected at any time of the day regardless of meals are 200 mg / dl or more, and (3) In the lower test, when the glucose concentration is 200 mg / dl or more, it can be diagnosed as having diabetes. Therefore, the goal of glycemic control to treat diabetes is to maintain fasting glucose 80-120mg / dl, 2-hour post-prandial blood sugar 100-140mg / dl and glycated hemoglobin (HbA1c) of less than 6.5%. .

In addition, to control blood glucose, two important tests, autologous glucose test and glycated hemoglobin test, should be continued. The self blood glucose test is one or more tests per day to know their blood sugar level accurately, because the blood glucose level indicating the immediate and short-term status can be planned and appropriately controlled diabetes.

The glycated hemoglobin test is just as important as the autologous blood sugar test, because the blood glucose levels of the last two to three months can determine how your blood sugar has been controlled. Glycated hemoglobin is a form of hemoglobin used to determine blood glucose (blood sugar) concentrations for a long period of time, and is formed by exposure of hemoglobin to high blood glucose states. In human blood, red blood cells with a life span of about 120 days are present. Hemoglobin in red blood cells combines with glucose to form glycated hemoglobin, or glycated hemoglobin.

Therefore, the quercetin according to the present invention can reduce blood sugar after eating and fasting as described above, can reduce the concentration of glycated hemoglobin in the blood, and also has an effect of suppressing weight gain, thereby preventing diabetes or diabetic complications. It can be used for prevention or treatment.

Therefore, the present invention can provide a composition for preventing or treating diabetes or diabetic complications containing quercetin or salts thereof as an active ingredient.

In the present invention, the diabetic complication may be selected from the group consisting of stroke, coronary heart disease, arteriosclerosis, and myocardial infarction cardiovascular disease.

In addition, the diabetes in the present invention may include both type 1 diabetes and type 2 diabetes, preferably type 2 diabetes.

The composition for preventing or treating diabetes mellitus or diabetic complications according to the present invention may include a pharmaceutically effective amount of quercetin compound alone or may include one or more pharmaceutically acceptable carriers, excipients or diluents. The pharmaceutically effective amount herein refers to an amount sufficient to prevent, ameliorate and treat the symptoms of diabetes or diabetic complications.

The pharmaceutically effective amount of quercetin according to the present invention is 0.5-100 mg / day / kg body weight, preferably 0.5-5 mg / day / kg body weight. However, the pharmaceutically effective amount may be appropriately changed according to the degree of diabetes or diabetic complication symptoms, the age, weight, health condition, sex, route of administration and duration of treatment of the patient.

In addition, "pharmaceutically acceptable" as used herein refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction, such as gastrointestinal disorders, dizziness, or the like when administered to a human. Examples of such carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives may be further included.

In addition, the compositions of the present invention may be formulated using methods known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatine capsules, sterile injectable solutions, sterile powders.

The composition for preventing or treating diabetes mellitus or diabetic complications according to the present invention may be administered through various routes including oral, transdermal, subcutaneous, intravenous or intramuscular, and the dosage of the active ingredient is determined by the route of administration, age, sex, It may be appropriately selected depending on various factors such as the weight and the severity of the patient.

In addition, the composition for preventing or treating diabetes mellitus or diabetic complications of the present invention can be administered in parallel with known compounds having the effect of preventing, improving or treating the symptoms of diabetes mellitus or diabetic complications.

Accordingly, the present invention can provide a medicament capable of preventing and treating the symptoms of diabetes or diabetic complications, including a composition containing quercetin or a pharmaceutically acceptable salt thereof as an active ingredient.

Furthermore, the composition for the prevention or improvement of diabetes or diabetes complications of the present invention can be used as a pharmaceutical composition for the purpose of preventing and improving the symptoms of diabetes or diabetes complications as described above, as well as the prevention of diabetes or diabetes complications And it can be used as a composition for food for the production of health functional food showing an improvement effect.

Therefore, the composition for food of the present invention can be easily utilized as a food, such as a main raw material, secondary ingredients, food additives, functional foods or beverages that are effective in preventing and improving symptoms of diabetes or diabetic complications.

As used herein, the term “food” refers to a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through a certain processing step, It includes all foods, food additives, functional foods and drinks.

Foods to which the composition for preventing and improving the symptoms of diabetes or diabetic complications according to the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, and functional foods. In addition, in the present invention, food includes special nutritional products (e.g., formulated milk, young, infant food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), bread, health supplements, seasonings. Foods (e.g. soy sauce, miso, red pepper paste, mixed soy sauce), sauces, confectionery (e.g. snacks), candy, chocolates, gums, ice creams, dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, Pickled foods (various kimchi, pickles, etc.), beverages (e.g., fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.), natural seasonings (e.g. ramen soup, etc.) are not limited thereto. The food, beverage or food additive may be prepared by a conventional production method.

In addition, the term "functional food" refers to the control of biological defense rhythms and disease prevention of food groups or food compositions that have added value to the food by using physical, biochemical, or biotechnological techniques to act and express the function of the food for a specific purpose. It means a food that is designed and processed to fully express the body's regulatory function regarding recovery and the like, and specifically, it may be a health functional food. The functional food may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.

In addition, in the present invention, the "beverage" refers to a generic term for drinking to quench thirst or to enjoy a taste and includes a functional drink. The beverage contains, as the essential ingredients, the composition for the prevention and amelioration of the symptoms of diabetes or diabetic complications as an essential ingredient, and there are no particular restrictions on the other ingredients, and various flavors or natural carbohydrates, such as ordinary drinks, may be added. It may contain as.

In addition, the food containing the composition for the prevention and improvement of the symptoms of diabetes or diabetic complications of the present invention in addition to the above-described flavors, coloring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors And fillers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The components may be used independently or in combination.

Furthermore, the present invention can provide a dietary supplement comprising quercetin and a food acceptable food supplement additive, which exhibits an effect of preventing or improving diabetes or diabetic complications.

In a food containing a composition for preventing and improving the symptoms of diabetes or diabetic complications of the present invention, the amount of the composition according to the present invention may comprise 0.001% to 90% by weight of the total food weight, preferably 0.1 It may be included in the weight% to 40% by weight, in the case of a beverage, it may be included in a ratio of 0.001g to 2g, preferably 0.01g to 0.1g based on 100ml, for health and hygiene purposes or health control In the case of long-term intake for the purpose may be less than the above range, since the active ingredient can be used in an amount above the above range because there is no problem in terms of safety is not limited to the above range.

Hereinafter, the present invention will be described in more detail with reference to Examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

< Example  1>

Quercetin  Hypoglycemic effect measurement

We used rats as animal models for in vivo experiments to investigate the hypoglycemic activity of quercetin compounds. In other words, Sprague-Dawley male rats with an average body weight of 150-180g were purchased from Hyochang Science Co., Ltd. and raised at the Inje University Animal Resource Center for about 7 days before the experiment. It was freely ingested, and reared at a temperature of 23 ± 2 ° C., 55 ± 10% humidity, and a 12 hour contrast cycle. All animal experiments were conducted according to the regulations of Inje University Animal Resource Center. In rats bred under the above conditions, The hypoglycemic effect was measured. First, male rats were divided into a control group (n = 7) and a quercetin-administered group (n = 7), and the control group was only starch (starch, 1 g / kg), and the quercetin-administered group was starch (1 g / g). Kg) and quercetin (50 mg / kg), and the composition of the sample dosage is shown in Table 1 below. 30, 60, 90, 120, 180 and 240 minutes after administration, the blood was collected from the tail vein of the mice, centrifuged at 1500 x g for 15 minutes, and plasma was collected and stored at -70 ° C. Subsequently, the glucose content (blood sugar) in the serum in the stored plasma was measured using a glucose oxidase enzyme method (Raabo E, Terkildsen TC, On the enzymatic determination of blood) using an assay kit (assay kit, Asan Pharmaceutical, Korea). glucose.Scand J Clin Lab Invest , 12, p.402, 1960), and the area of the blood glucose change curve was calculated. All experimental results were expressed as mean ± SD, and statistically, the Student's t-test was used, and the results of p <0.05 were judged to be significant. In addition, after the administration of quercetin, the weight measurement results of the rats are shown in Table 2 below, Table 3 shows the area of the blood glucose change curve, and the graph of the change in blood glucose over time is shown in FIG. 1.

Composition of Sample Dosage Experimental group Furtherance Control group Starch 1.0 g / Kg + distilled water Quercetin-administered group Starch 1.0 g / Kg + quercetin 0.05 g / kg + distilled water

Weight change measurement result Kinds Control group Quercetin-administered group Weight (g)  288.6 ± 26.5  281.6 ± 30.6

Area measurement result of blood glucose change curve Kinds Area of blood glucose change curve after meal (mgmin / dl) Control group  16,377 ± 1,940 Quercetin-administered group 10,674 ± 751 ^*

^* p <0.05

As a result, as shown in Table 2, there was no significant difference in weight change in the group administered quercetin and the control group not administered. On the other hand, as a result of measuring the blood glucose level of the quercetin-administered group and the control group not administered, as shown in FIG. 1, the blood glucose levels of the quercetin-treated group were significantly decreased with time compared to the control group. The area of the post-prandial glycemic change curve was also significantly decreased in the quercetin-treated group compared to the control group (see Table 3).

Therefore, the present inventors have found that the quercetin of the present invention has an activity that can effectively suppress postprandial blood glucose in vivo.

< Example  2>

Diabetes Animal Model Quercetin  Weight loss effect measure

In vivo Quercetin In vivo ) blood glucose control effect is divided into 7 groups of 5 weeks-old db / db mice of type 2 diabetes, divided into two groups, and separated by the ovary method so that the average blood sugar of the control group and the experimental group is similar to the control group as shown in the following table. The AIN-93G base diet described in 4 was administered to the experimental group for 6 weeks with a diet containing 0.08% quercetin in the base diet. Diet and drinking water freely ( ad libitum ), the temperature and humidity of the breeding room were maintained at 20 ~ 25 ℃, 50 ~ 60%, respectively, the contrast was turned on and off every 12 hours. Animal weight and dietary intake were measured twice and three times a week, respectively. In addition, the experimental animals were sacrificed at the 6th week of diet, and the animals were fasted for 12 hours before sacrifice, suffocated with carbon dioxide gas, and the heart was injected with a syringe containing 10 mg of EDTA (ethylene diamine tetra acetic acid). Blood was collected at. Blood was collected by centrifugation at 3,000 rpm for 15 minutes to collect plasma and stored at -70 ° C. All experimental results were expressed as mean ± SD, and statistical treatment was Student's t-test. ), The significance test was carried out at p <0.05 or less, and after six weeks of dietary supply of quercetin, the weight of each mouse was measured, and the results are shown in Table 5 below.

Diet ingredient Control diet Quercetin Diet Corn starch ^{1 )} 39.8 39.8 Luxury starch 13.2 13.2 Casein ^{2 )} 20.0 20.0 Soybean oil ^{3 )} 7.5 7.5 α-cellulose ^{4 )} 6.3 6.3 Sucrose ^{3 )} 10.0 10.0 Mineral mixtures ^{5 )} 3.5 3.5 Vitamin mixtures ^{6 )} One One L-cystine ^{2 )} 0.3 0.3 Choline Bitartrate ^{4 )} 0.25 0.25 T-butylhydroquinone ^{7 )} 0.0014 0.0014 Quercetin ^{8 )} 0 0.08 ¹⁾ Target company, Korea
²⁾ ICN Biochemical, USA
³⁾ CheilJedang, Korea
⁴⁾ Sigma, USA
⁵⁾ AIN-93G Mineral mix., ICN Pharmaceuticals Inc., USA
⁶⁾ AIN-93G vitamin mix., ICN Pharmaceuticals Inc., USA
⁷⁾ Fluka Co., USA
⁸⁾ Freeze-dried and milled

Weight measurement results Kinds Control group Experimental group Weight (g)  41.1 ± 1.9 38.2 ± 2.0 ^*

^* p <0.05

As shown in Table 5, the weight of the quercetin-administered group was found to be 38.2 ± 2.0g, whereas the weight of the control group not administered quercetin was 41.1 ± 1.9g. That is, when quercetin was administered to a diabetic animal model, it was found that the weight loss effect.

< Example  3>

Quercetin  Measurement of plasma glucose concentration improvement effect

The present inventors can confirm that the quercetin compound of the present invention can reduce the weight of diabetic-induced mice through the results of the above embodiments, and could be expected to have an effect of improving, preventing and treating diabetes, Quercetin-induced plasma glucose up-regulation activity was measured in diabetic animal models. After the long-term intake of quercetin for 6 weeks in the type 2 diabetic mouse model used in Example 2 for the measurement, the glucose oxidase enzyme method (Raabo) using an assay kit (assay kit, Asan Pharmaceutical, Korea) E, Terkildsen TC, On the enzymatic determination of blood glucose. Scand J Clin Lab Invest 12: 402, 1960), the glucose content in plasma was measured.

As a result, as shown in Figure 2, the experimental group ingested quercetin for 6 weeks, the fasting blood glucose was 384.9 ± 37.6 mg / dL, the control group was not administered quercetin was 463.5 ± 48.3 mg / dL .

Therefore, the present inventors have found that quercetin can significantly reduce fasting blood glucose, and furthermore, quercetin has been shown to be able to maintain the effect of reducing blood glucose even after ingesting quercetin for a long time. It was found that the symptoms of diabetes can be improved and further used for treatment.

< Example  4>

Quercetin  blood Saccharification  Determination of hemoglobin concentration reduction effect

In general, glycated hemoglobin accounts for about 3-6% of normal hemoglobin, but it is known that the number of diabetic patients is 2-3 times higher than normal. In diabetics, hyperglycemia continues to promote nonspecific glycosylation of proteins and develop diabetic microvascular complications. Hemoglobin also increases glycation hemoglobin levels due to nonspecific glycosylation. Therefore, glycated hemoglobin is used as an indicator of long-term glycemic control in diabetic patients. Therefore, the inventors of the present invention, the experimental group and the non-administered quercetin administered to the type 2 diabetic mouse model used in Example 2 to determine whether the quercetin compound of the present invention has an effect of reducing the concentration of such glycated hemoglobin Blood was collected from each column and column chromatograph was performed to measure the concentration of glycated hemoglobin. In other words, 50 μl of hemolyzed reagent (hemolyzing reagent, BioSystem, Spain) was added to 50 μl of blood collected from the experimental group and the control group, and 50 μl of the hemolyzed specimen obtained by standing at room temperature for 10 minutes was filled with cation-exchange resin. Into the old column. HbA _1C The base wall was washed with 200 µl of washing reagent, 2 mL of the same reagent was drained through the column, and the fraction eluted with 4 mL of eluting reagent was recovered. Then, 12 mL of the eluent was added to 50 μl of the hemolytic sample to prepare total Hb. The absorbance of HbA _1C and total Hb was measured by distilled water at 415 nm in the spectrophotometer, and then substituted into the following equation to calculate glycated hemoglobin. The results are shown in FIG. 3.

[Equation]

HbA _{1 C} (%) = A / (3 × B) × 100

A = absorbance of HbA _1C

B = absorbance of total Hb

As a result, the blood glycated hemoglobin concentrations of the experimental group ingested quercetin in the type 2 diabetic animal model for 6 weeks and the control group not treated with quercetin were 6.3 ± 0.5% and 7.2 ± 0.6%, respectively. Significantly decreased.

Accordingly, the present inventors have found that the quercetin of the present invention has an effect of controlling blood glucose and ultimately can prevent and treat diabetes and diabetic complications.

So far I looked at the center of the preferred embodiment for the present invention. Those skilled in the art will appreciate that the present invention can be implemented in a modified form without departing from the essential features of the present invention. Therefore, the disclosed embodiments should be considered in descriptive sense only and not for purposes of limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope will be construed as being included in the present invention.

Claims (6)

Quercetin (Quercetin) or a salt thereof composition for lowering blood sugar containing as an active ingredient. The method of claim 1,
The quercetin inhibits weight gain, decreases the concentration of glucose in the plasma or decreases the concentration of glycated hemoglobin in the blood. A composition for preventing or treating diabetes mellitus or diabetic complications comprising quercetin or a salt thereof as an active ingredient. The method of claim 3,
The diabetic complication is a composition for preventing or treating diabetes or diabetic complications, characterized in that selected from the group consisting of stroke, coronary heart disease, arteriosclerosis and myocardial infarction cardiovascular disease. The method of claim 3,
The diabetes is a composition for the prevention or treatment of diabetes mellitus or diabetic complications, characterized in that the type 2 diabetes. A dietary supplement comprising quercetin and a food-acceptable food supplement that exhibits the effect of preventing and improving diabetes or diabetic complications.

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