JP2007126390A - Agent for reducing blood glucose level - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new agent for reducing a blood glucose level, capable of safely and precisely controlling the blood glucose level. <P>SOLUTION: The agent for reducing the blood glucose level contains resveratrol as an active ingredient. The food and drink or the fodder for preventing diabetes or ameliorating the symptom contains the agent added thereto, preferably ≥0.005 wt.% resveratrol added to the food and drink. The agent for reducing the blood glucose level exhibits excellent blood glucose level-reducing activities and activities for ameliorating glucose tolerance disorder in a mouse model of type II diabetes. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to a blood glucose level-lowering agent containing resveratrol and a food or drink or feed for preventing diabetes or improving symptoms containing the same.

Resveratrol, a kind of polyphenol, is a phytoalexin (antibacterial substance) having an antioxidant action contained in grapes and red wine. This substance has a heart disease prevention and improvement effect (see Patent Document 1), antioxidant activity (see Non-Patent Document 1), anti-inflammatory effect and cerebral thrombosis prevention (see Patent Document 2), anti-cancer effect (Non-Patent Document 2). Reference) and the effect of inhibiting the progression of cerebral tissue damage after cerebral infarction (see Patent Document 3). Due to the physiological effects of resveratrol, it has been considered that the medium wine consumption is a substance involved in the so-called “French paradox”, which has a negative correlation with the risk of cardiovascular disease, stroke and dementia.

The therapeutic agents for diabetes are roughly divided into oral drugs and insulin. Furthermore, oral drugs are classified into insulin secretagogues, insulin resistance improvers, and α-glucosidase inhibitors depending on the mechanism of action. Insulin secretion-promoting drugs include sulfonylurea (SU) drugs and phenylalanine derivative drugs. SU drugs block _KATP channels from the outside and activate voltage-dependent Ca ²⁺ channels through cell membrane depolarization. As a result, Ca ²⁺ flowing into the cell promotes insulin secretion. Insulin resistance ameliorating drugs include thiazolidine derivatives (TZD) drugs and hyguanide drugs. The former acts as a ligand for the peroxisome proliferator-responsive receptor γ (PPARγ), which is an expression of the latter. It is considered that AMP-dependent kinase is partly involved in improving insulin resistance. However, excessive administration and long-term use may lead to obesity, worsening of insulin resistance, inadequate blood sugar level control, and the like.

JP 2001-510777 A JP-A-9-165331 JP 2003-300904 A Fauconneau, B. et al. Comparative study of radical scavenger and antioxidant properties of phenolic compounds from Vitis vinifera cell cultures using in vitro test.Life Sci. 61, 2103-2110 (1997) Jang, M. et al. Cancer chemopreventive activity of resveratrol, anatural product derived from grapes. Science 275, 218-220 (1997)

An object of the present invention is to provide a novel blood glucose level-lowering agent that can control blood glucose level more safely and reliably.

As a result of intensive studies to solve the above-mentioned problems, the present inventors orally administered resveratrol to a type II diabetes model mouse significantly reduced the blood glucose level of the mouse and improved glucose tolerance dysfunction. I found out that That is, it was found that oral administration of an appropriate amount of resveratrol was effective in preventing diabetes and improving symptoms, and completed the present invention.

That is, the present invention
(1) a blood sugar level-lowering agent containing resveratrol as an active ingredient,
(2) The blood sugar level-lowering agent according to (1), wherein the resveratrol is derived from grapes, peanuts or Japanese knotweed,
(3) A food or drink for preventing diabetes or improving symptoms, to which the blood sugar level-lowering agent according to (1) or (2) is added,
(4) The food or drink according to (3), wherein resveratrol is added to the food or drink by 0.005% by weight or more,
(5) A feed for preventing diabetes or improving symptoms, to which the blood sugar level-lowering agent described in (1) or (2) is added, and (6) 0.005% by weight or more of resveratrol in food and drink The feed according to (5),
About.

Resveratrol contained in the blood sugar level lowering agent of the present invention has an effect of lowering blood sugar level, suppressing the increase of blood sugar level, and lowering the blood sugar level of abnormal hyperglycemia which is the main symptom of diabetes. Have. Further, even when resveratrol is administered, side effects such as abnormal increase in body weight are not observed, and there is an effect of improving impaired glucose tolerance. Therefore, diabetes can be effectively prevented or symptoms can be improved.

Hereinafter, the present invention will be described in more detail. Resveratrol, which is an active ingredient of a blood sugar level-lowering agent, a food or drink for preventing or improving symptoms of diabetes, or a feed therefor, is a natural ingredient contained in grape skins, seeds and the like that are the raw materials for red wine Therefore, safety against human livestock is high. Furthermore, resveratrol uses a variety of purification methods such as extraction methods using organic solvents such as ethanol, acetone, and ethyl acetate, and chromatography using silica gel, adsorption resin, etc. Can be isolated. It can also be produced by an organic synthesis method.

The method for carrying out the present invention will be specifically described. First, the administration route of the blood sugar level-lowering agent of the present invention is preferably oral. The preferred dosage is 0.01-100 mg / kg body weight / day for mice, and for humans, it is determined in consideration of the correlation with mice or the degree of diabetes in humans. However, 0.1-100 mg / kg body weight / day is preferable.

Examples of the dosage form of the blood sugar level-lowering agent of the present invention include ampoules, tablets, capsules, granules, fine granules, powders, drinks and the like, but are not limited to specific dosage forms. . Moreover, it is preferable that the preferable content of resveratrol in a formulation shall be 0.005 weight% or more with respect to the formulation whole quantity. In these dosage forms, various components usually used for formulation are optionally used. For example, starch such as corn starch, dextrin, lactose, inorganic salts, glucose, mannitol, magnesium stearate, talc, cellulose derivatives , Gelatin, citric acid and the like.

Moreover, since resveratrol has a dietary experience, it can be added to foods or feeds to make foods or drinks or feeds for preventing diabetes or improving symptoms. In such a case, it is usually about 0.01 to 50% by weight, preferably about 0.1 to 10% by weight, and it is usually about 0.01 to 50% by weight, preferably to food and drink. About 0.1 to 10% by weight may be added.

In general, the action of lowering the blood glucose level and suppressing the increase of the blood sugar level from a hyperglycemic state is an in vivo test using a diabetes model mouse, that is, administering a test substance to a diabetes model mouse and administering it for a certain period of time. It can be evaluated by a test that measures the blood glucose level and the amount of glycated hemoglobin at each stage. Glycated hemoglobin is composed of components of hemoglobin A1a, hemoglobin A1b, and hemoglobin A1c, and has a tendency to remain in the blood for a long period of time, so that it becomes an excellent marker of glycated protein in blood. Among them, the value of hemoglobin A1c (HbA1c) reflects the effectiveness of blood glucose treatment as an index of the average blood glucose control level for 6 to 8 weeks before measurement, and is therefore an effective marker for the diagnosis of diabetes. In combination with the measurement of the value, it is used for the diagnosis of diabetes and the measurement of the degree of progression. According to the test method described above, the blood sugar level lowering agent of the present invention significantly lowers the blood sugar level and the amount of glycated hemoglobin, and has an excellent blood sugar level lowering effect, as compared with the control group.

EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not restrict | limited at all by these.

Example 1 Confirmation of blood glucose level lowering effect in type II diabetes model mouse
6-week-old male db / db mice (purchased from Japan Charles River), which are type II diabetes model mice, were divided into 5 groups per group, and normal blood glucose levels were measured in advance, and hyperglycemia (300 mg / dl). The first group (db / db mouse control group) and the second group (resveratrol-administered db / db mouse group) were freely given the CRF-1 chow (oriental yeast industry) used as the basic food, 600 μl of resveratrol samples prepared to 3.5 μg / ml with 0.5% CMC in the first group and 0.5% CMC in the second group, once a day for 20 days. And gavage using a sonde. After breeding for 20 days, blood was collected from the tail vein, and the blood glucose level was measured with a one-touch ultra (manufactured by LIFESCAN). In addition, blood was collected from the orbital vein using a hematocrit tube, and the amount of glycated hemoglobin (HbA1c) was measured using Micromat II (manufactured by Sysmex Corporation). The results of this test are shown in Table 1 and FIG.

As a result, the blood glucose level was significantly decreased in the second group as compared with the first group. Therefore, it has been found that administration of resveratrol is effective for lowering blood glucose level. Moreover, since the 2nd group also decreased from the 1st group also about the amount of glycated hemoglobin, it was confirmed that the fall of the blood glucose level was maintained by the administration of the resveratrol to a mouse | mouth.

Example 2 Glucose tolerance disorder improving effect confirmation test in glucose tolerance test using type II diabetes model mouse First group (db / db mouse control group) and second group (resveratrol-administered db / db mouse group) CRF-1 solid feed (produced by Oriental Yeast Co., Ltd.) used as a basic food was freely given, and the first group contained 0.5% CMC and the second group contained 0.5% CMC at 3.5 μg / ml. Each of the resveratrol samples prepared in (1) was orally administered by gavage once a day using a sonde. Fourteen days after the start of administration, the mice were fasted for 20 hours, and a glucose tolerance test was performed. Glucose is orally administered at a rate of 2 g / kg body weight, blood is collected from the tail vein of the mouse immediately before sugar load (0 minutes), 30 minutes, 60 minutes, and 120 minutes after the load, and the blood glucose level is measured using a one-touch ultra. did. The results are shown in Table 2 and FIG.

Compared with the first group, the second group showed a significantly lower blood sugar level 30 minutes after the sugar load, and also showed a lower blood sugar level thereafter. From this, it was confirmed that resveratrol is effective in improving impaired glucose tolerance.

Example 3 CRF-1 chow diet used as a basic diet in group II type diabetes mouse model weight change (db / db mouse control group) and group 2 (resveratrol-administered db / db mouse group) (Oriental Yeast Industry Co., Ltd.) was given freely, and resveratrol samples prepared to 3.5 μg / ml with 0.5% CMC for the first group and 0.5% CMC for the second group were each 600 μl. Once a day, it was administered by oral gavage with a sonde for 20 consecutive days. The body weight during the breeding period was measured and compared with the control group. The results are shown in FIG.

In the resveratrol administration group of the second group, the weight gain was almost the same as that in the non-administration group of the first group, and the weight change was considered normal. Therefore, side effects that caused abnormalities in body weight by resveratrol administration were not confirmed.

It is a figure which shows the blood glucose level lowering effect of resveratrol. It is a figure which shows the glucose tolerance disorder improving effect of the resveratrol in a glucose tolerance test. It is a figure which shows the weight change after a resveratrol administration.

Claims (6)

A blood sugar level-lowering agent containing resveratrol as an active ingredient. 2. The blood sugar level-lowering agent according to claim 1, wherein the resveratrol is derived from grape, peanut or Japanese knotweed. A food or drink for preventing diabetes or improving symptoms, to which the blood sugar level-lowering agent according to claim 1 or 2 is added. The food / beverage products of Claim 3 which added the resveratrol 0.005weight% or more in food / beverage products. A feed for preventing diabetes or improving symptoms, to which the blood sugar level-lowering agent according to claim 1 or 2 is added. The feed according to claim 5, wherein resveratrol is added to the food or drink in an amount of 0.005% by weight or more.

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