JP5905246B2 - Insulin secretagogue - Google Patents

Description

  The present invention relates to an insulin secretagogue, and in particular, to an insulin secretagogue comprising a polyglycerol fatty acid ester having a specific range of HLB as an active ingredient.

  Diabetes is roughly classified into type I diabetes (insulin-dependent diabetes) and type II diabetes (non-insulin-dependent diabetes). The majority of diabetes affected by Japanese is type II diabetes. Type II diabetes occurs when symptoms such as insulin secretion failure in which the amount of insulin secreted decreases and insulin resistance in which the action of insulin to lower blood sugar weakens progress. These symptoms are greatly related to genetic factors and environmental factors such as unbalanced diet, overeating, lack of exercise, and stress.

  In recent years, the number of patients with type II diabetes has increased, and it is already said that the number of patients with type II diabetes has already reached 20 million including the diabetic reserve army. Therefore, not only the care of diabetics but also the prevention that does not shift the diabetic reserve to diabetes is an important issue.

  In general, treatment of type II diabetes is based on diet therapy and exercise therapy, and drug therapy is performed. As pharmacotherapy for type II diabetes in Japan, sulfonylurea agents (SU agents) that promote insulin secretion are often used. This is because Japanese insulin secretion ability is lower than that of Westerners. However, the SU agent has problems of side effects such as hypoglycemia, pruritus, rash, and weight gain. Since it is necessary to carry out pharmacotherapy for diabetes for a long period of time, there has been a demand for the development of an insulin secretagogue that does not cause side effects even when continuously taken.

  As such an insulin secretion promoter, for example, Patent Document 1 reports that an extract obtained from the skin portion of white sweet potato tuber is effective.

Japanese Patent No. 3767007

  The present invention has been made in view of the above circumstances, and its purpose is to provide an insulin secretion promoter that is highly safe and has no side effects even when continuously ingested, and is effective in preventing diabetes. It is to be.

  In the process of repeating the research for solving the above-mentioned problems, the present inventor gives a sugar load to rats, and at the same time, when an oil and fat and a polyglycerol fatty acid ester having a specific HLB are administered, only the oil and fat are given. As compared with the case of administration, the inventors found that the increase in plasma insulin concentration was remarkable, and completed the present invention.

  Specifically, the present invention provides the following.

  (1) Insulin secretion promoter characterized by containing polyglycerin fatty acid ester of HLB 4-15 as an active ingredient.

  (2) The insulin secretion promoter according to (1), which contains the polyglycerin fatty acid ester together with fats and oils.

  (3) The insulin secretion promoter according to (1), which is used in combination with fats and oils.

  (4) The insulin secretion promoter according to any one of (1) to (3), which is used for prevention or treatment of type II diabetes.

  Since the insulin secretion promoter of the present invention is excellent in the insulin secretion promoting action, it is particularly effective for the prevention or treatment of type II diabetes. Moreover, according to the insulin secretion promoter of this invention, since polyglycerin fatty acid ester is contained as an active ingredient, since it is highly safe and there is no fear of a side effect, it can be used continuously in comfort.

It is a figure which shows the measurement result of the plasma insulin concentration in the (A) hexastearate pentaglycerin (HLB: 4) administration trial, and the measurement result of the plasma insulin concentration in the (B) trioleate pentaglycerin (HLB: 7) administration trial. . It is a figure which shows the measurement result of the plasma insulin density | concentration in a trial administration of dekaoleic acid decaglycerol (HLB: 3). It is a figure which shows the measurement result of the plasma insulin density | concentration in a monooleic-acid tetraglycerin (HLB: 8.8) trial.

  Hereinafter, specific embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and may be implemented with appropriate modifications within the scope of the object of the present invention. can do.

  The insulin secretagogue of the present invention is characterized by containing a polyglycerol fatty acid ester as an active ingredient. The HLB of the polyglycerin fatty acid ester is 4-15, preferably 4-9. The insulin secretion promoter of the present invention may contain one or more polyglycerol fatty acid esters having an HLB value of 4 to 15. Here, the HLB value is a numerical value representing the balance between hydrophilicity and hydrophobicity in the surfactant. For example, the HLB value is determined by the method described in “Revised Third Edition, Yuki Kagaku Handbook” (edited by the Japan Oil Chemistry Association, published by Maruzen). Can be measured.

  In the insulin secretagogue of the present invention, the fatty acid constituting the polyglycerol fatty acid ester is not particularly limited, and the carbon number thereof is usually 6 to 24, preferably 14 to 20, and more preferably 16 to 20 saturation. And / or unsaturated fatty acids. Specifically, caproic acid (n-hexanoic acid), caprylic acid (n-octanoic acid), capric acid (n-decanoic acid), lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, Examples thereof include linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, erucic acid, and lignoceric acid.

  In the insulin secretion promoter of the present invention, as long as the HLB value is 4 to 15, a commercially available polyglycerol fatty acid ester may be used, or a polyglycerol fatty acid ester produced by a conventionally known method may be used. The manufacturing method of polyglycerol fatty acid ester is not specifically limited, For example, conventionally well-known methods, such as esterification of glycerol and a fatty acid, and transesterification of glycerol and fats and oils, are mentioned. Although an example of the manufacturing method of polyglycerol fatty acid ester is shown below, it is not limited to this. First, glycerin and sodium hydroxide (catalyst) are mixed and dried while reducing the pressure at 90 ° C. or higher, and then polymerized at 200 to 270 ° C. to obtain polyglycerin. The obtained polyglycerin and fatty acid are charged into a reaction vessel at an appropriate ratio, and a sodium hydroxide solution is added as a catalyst. Next, the mixture is heated to a temperature of 200 ° C. or higher under a nitrogen stream and reacted for about 1 to 3 hours, and then the internal temperature is set to 250 ° C. or higher and reacted for 3 to 5 hours. Then, it cools to normal temperature and refine | purifies by a conventional method, and can obtain polyglycerol fatty acid ester. In addition, the HLB value of polyglycerol fatty acid ester can be adjusted with a conventional method.

  As a commercial item of the above-mentioned polyglycerin fatty acid ester, for example, “Sunsoft A-186E”, “Sunsoft Q-175S”, “Sunsoft Q-185S”, “Sunsoft Q-17B” manufactured by Taiyo Kagaku Co., Ltd. "Sunsoft Q-18B", "Sunsoft Q-18D", "Sunsoft A-173E", "Sunsoft Q-182S", "Sunsoft Q-17S", "Sunsoft A-171E" “Soft A-121E”, “Sunsoft Q-14S” and the like.

  In the insulin secretion promoter of the present invention, the properties of the polyglycerin fatty acid ester are not particularly limited, and examples thereof include oil, paste, powder, and granule.

  The polyglycerin fatty acid ester is an ester obtained from polyglycerin and a fatty acid derived from natural vegetable oils and fats, and has been conventionally used as an emulsifier for food. It has long been recognized as a food additive, is highly safe, and has no known adverse side effects. Since the insulin secretion promoter of the present invention contains such a polyglycerin fatty acid ester as an active ingredient, there is no concern about side effects even if it is continuously taken.

  The insulin secretagogue of the present invention preferably contains the polyglycerin fatty acid ester together with fats and oils. The polyglycerin fatty acid ester exhibits an insulin secretion-promoting effect when used in combination with fats and oils when ingesting sugar (glucose). Therefore, according to the insulin secretion promoter of the present invention containing the polyglycerin fatty acid ester together with fats and oils, the insulin secretion promoting effect can be more reliably exhibited. The type of oil is not particularly limited, but is preferably vegetable oil, such as soybean oil, rapeseed oil, corn oil, coconut oil, palm oil, rice oil, sesame oil, cottonseed oil, sunflower oil, safflower oil , Flaxseed oil, perilla oil, olive oil, peanut oil, grape seed oil, macadamia nut oil, hazelnut oil, pumpkin seed oil, walnut oil, coconut oil, tea seed oil, sesame oil, borage oil, rice bran oil, wheat germ oil, etc. 1 A seed | species or 2 or more types of mixed fats and oils are mentioned. These fractionated oils, hydrogenated oils, transesterified oils, and the like can also be used. Among these, oils and fats that are liquid at 20 ° C. are preferable from the viewpoint of handling properties.

  When the insulin secretion promoter of the present invention contains the polyglycerin fatty acid ester together with fats and oils, the ratio (mass ratio) between the fats and oils and the polyglycerin fatty acid ester is 99.5: 0.5 to 98: 2. It is preferable that If it is the said range, the insulin secretion promotion effect effective in diabetes prevention etc. can be acquired.

  The insulin secretion promoter of the present invention may contain a known emulsifier other than the polyglycerin fatty acid ester as long as the effects of the present invention are not impaired. Examples of the emulsifier include sorbitan fatty acid ester, polysorbate, condensed ricinolein fatty acid ester, monoglycerin fatty acid ester, lecithin, lysolecithin, saponin, and plant sterols.

  The polyglycerin fatty acid ester exerts an action of significantly increasing the plasma insulin concentration when sugar is ingested when used in combination with fats and oils. The insulin secretagogue of the present invention containing such a polyglycerin fatty acid ester as an active ingredient effectively acts on animals including humans who fall under diabetes or its reserves that need to increase the amount of insulin secretion. In particular, it is considered to be effective for the prevention or treatment of type II diabetes accompanied by insulin secretion deficiency in which the amount of insulin secretion decreases. Here, “prevention” means, for example, suppression or delay of onset, and “treatment” means, for example, delay of progression, alleviation, reduction, improvement, etc. of symptoms.

  Since drug therapy for diabetes needs to be carried out continuously for a long period of time, the drug is required to have no side effects even when taken continuously. Since the insulin secretion promoter of the present invention contains polyglycerin fatty acid ester as an active ingredient, which is highly safe and has no side effects, it can be taken continuously with peace of mind. In addition, since it is easy to control the dose, it is suitable for drug therapy combining diet therapy and exercise therapy in the treatment of type II diabetes.

  The administration route of the insulin secretagogue of the present invention is preferably oral administration. This is because, after being decomposed, most of the polyglycerol fatty acid ester is absorbed into the body through the mucous membrane of the intestinal tract (small intestine). Examples of the preparation suitable for oral administration include capsules, tablets, pills, powders, fine granules, granules, liquids, syrups and the like. It is preferable to make the preparation in the form of a pharmaceutical composition comprising the polyglycerin fatty acid ester as an active ingredient and a pharmacologically and pharmaceutically acceptable additive. Furthermore, it is good also as a formulation in the form of the pharmaceutical composition containing the said fats and oils. Examples of pharmacologically and pharmaceutically acceptable additives include excipients such as glucose, lactose, crystalline cellulose and starch, disintegrants, binders, coating agents, pigments, diluents, etc. A substance that is commonly used in the field and does not react with the polyglycerin fatty acid ester is used.

  As described above, since the insulin secretagogue of the present invention is highly safe and has no side effects like existing insulin secretagogues, the dose of the existing drug can be reduced by using it in combination with the existing drug. , These can reduce side effects. Combinations with other drugs may be included in the same pharmaceutical composition as in the case of a combination drug, or may be included in separate pharmaceutical compositions.

  The dose of the insulin secretagogue of the present invention can be appropriately selected according to various conditions such as patient symptoms, prevention or treatment, age, weight, administration method, administration period and the like. For example, for the purpose of treatment of humans (adult 60 kg), the effective amount is usually 5 to 20 mg / kg body weight / day as a polyglycerol fatty acid ester, and this amount is divided into one or several times. May be administered. The insulin secretagogue of the present invention is effective when administered before or during a meal.

  The polyglycerin fatty acid ester can be used for the production of a food for promoting insulin secretion for diabetic patients or their reserves. For example, the polyglycerin fatty acid ester can be ingested as a health food by filling or processing soft capsules alone or together with the oil or fat. In addition, for example, by processing the polyglycerin fatty acid ester and the fats and oils into a liquid emulsified oil or fat, or by further processing the liquid emulsified fats and oils into a powder form, these are further consumed in general foods, It can also be taken indirectly by processing.

  The general food that can be produced using the polyglycerin fatty acid ester is not particularly limited. For example, bread, cake, cookies, biscuits, donuts, muffins, scones, chocolate, snacks, whipped cream, Ice cream bread and confectionery, fruit juice drinks, energy drinks, sports drinks and other drinks, soups, dressings, sauces, mayonnaise, butter, margarine, prepared margarine and other seasoned processed foods, fat spreads, shortening, bakery mix , Stir-fried oil, frying oil, fried food, processed meat products, frozen food, fried food, noodles, retort food, liquid food, swallowed food, and the like.

  When the above-mentioned polyglycerin fatty acid ester is used for the production of a food for promoting insulin secretion for diabetics or their reserves, the daily intake per adult (body weight 60 kg) is, for example, polyglycerin. The fatty acid ester is preferably 5 to 20 mg / kg body weight.

  The insulin secretion promoter of the present invention containing the polyglycerin fatty acid ester as an active ingredient is preferably used in combination with fats and oils. The polyglycerin fatty acid ester exerts an action of significantly increasing the plasma insulin concentration when sugar is ingested when used in combination with fats and oils. In order for the polyglycerin fatty acid ester to be used in combination with fats and oils, for example, as described above, the polyglycerin fatty acid ester is contained in the agent together with fats or oils, or when the fats and oils are not contained in the agent. Even if it is a case, if it is not included in an appropriate amount, the fats and oils may be taken separately as food.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention does not receive a restriction | limiting at all by these description.

[Test Example 1] Examination of plasma insulin secretion promoting effect (1)
The effect of polyglycerin fatty acid ester on plasma insulin secretion was investigated by administering fat or oil and pentaglycerin hexastearate (HLB: 4), which is a polyglycerin fatty acid ester, simultaneously with glucose loading to rats. It was.

<Production Example 1> Production method of sample 1 In 10 ml of 40% glucose (D (+)-Glucose, manufactured by Wako Pure Chemical Industries, Ltd.) solution, fats and oils (trade name: Nissin Canola Oil, long-chain fatty acid triglyceride (LCT), JP 2 g of purified oilio group) and 200 mg of bovine serum albumin (manufactured by SIGMA) were added, and the resulting solution was sonicated while cooling on ice (2 sets for 5 minutes, total 10 minutes), sample 1 was obtained.

<Production Example 2> Production method of Sample 2 To 10 ml of a 40% glucose (D (+)-Glucose, manufactured by Wako Pure Chemical Industries) solution, pentaglycerin hexastearate (trade name: Sunsoft A-186E) as a polyglycerin fatty acid ester , HLB: 4, manufactured by Taiyo Kagaku Co., Ltd.) 20 mg, fats and oils (trade name: Nisshin Canola Oil, long chain fatty acid triglyceride (LCT), manufactured by Nisshin Oillio Group), and 200 mg of bovine serum albumin (manufactured by SIGMA) Were added, and the obtained solution was sonicated while cooling on ice (2 sets of 5 minutes, total 10 minutes) to obtain Sample 2.

  Seven-week-old SD male rats (purchased from Japan SLC) were used in the test. After the rats (11 rats) were acclimated for 1 week, a glucose tolerance test in which samples 1 and 2 were administered at 8 and 9 weeks of age was performed by the crossover method. That is, a crossover method was employed in which a second glucose tolerance test was performed after a first glucose tolerance test with a one-week Wash-Out period so that the effects of polyglycerin fatty acid esters could be compared in the same individual. During the breeding period, the animals were individually raised in a stainless steel mesh cage in an environment of a temperature of 23 ± 1 ° C., a humidity of 50 ± 10%, and a 12-hour light / dark cycle (8:00 to 20:00 lighting). Water and solid feed (trade name: PicoLab Rodent Diet 20 5053, manufactured by SLC, Japan) were freely ingested. Fasting was performed from 17:00 on the day before the test, and administration was started from 10:00 on the day of the test.

  In the test, a “control trial (sample 1 administration trial)” in which fat and oil are administered at the same time as the sugar load, and an oil and fat and polyglycerin fatty acid ester, pentaglycerin hexastearate (HLB: 4), are administered at the same time as the sugar load. The test was conducted in two trials, “Triglyceride hexastearate (HLB: 4) administration trial (sample 2 administration trial)”. Samples 1 and 2 were orally administered to rats using a sonde. The dose was 6 μl / g rat body weight. The final dose was 2 g of carbohydrate, 1 g of lipid, and 0.01 g of pentaglycerin hexastearate per kg body weight of the rat.

  Then, blood was collected from the tail vein before administration and 20 minutes after administration, and the plasma insulin concentration (ng / ml) was measured. The plasma insulin concentration was measured by ELISA using a commercially available kit (trade name: Rat Insulin ELISA kit, manufactured by Mercodia). The test results are shown in FIG. The amount of increase in plasma insulin concentration in the pentaglycerin hexastearate (HLB: 4) administration trial is a relative value (%) where the average value of the increase in plasma insulin concentration in the control trial is 100, and the average value of the relative values ± Expressed in standard error. The Student t-test test was used for the significant difference test between trials, and it was judged that there was a significant difference with a risk rate of less than 5%.

  As shown in FIG. 1 (A), the amount of increase in plasma insulin concentration in the pentaglycerin hexastearate (HLB: 4) administration trial was significantly higher (P <0.01) than in the control trial. From this, it became clear that according to pentaglycerin hexastearate, which is a polyglycerol fatty acid ester having an HLB value of 4, insulin secretion into plasma is promoted. In addition, the average value (absolute value) of the plasma insulin concentration increase in the control trial is 1.33 ± 0.13 ng / ml, and the average plasma insulin concentration increase in the pentaglycerin hexastearate (HLB: 4) administration trial The value (absolute value) was 1.65 ± 0.11 ng / ml.

[Test Example 2] Examination of plasma insulin secretion promoting effect (2)
The effect of polyglycerin fatty acid ester on plasma insulin secretion was examined by administering fat or oil and fat and polyglycerin fatty acid ester trioleic acid pentaglycerin (HLB: 7) simultaneously with glucose loading. It was.

<Production Example 3> Production method of Sample 3 To 10 ml of 40% glucose (D (+)-Glucose, manufactured by Wako Pure Chemical Industries) solution, pentaglycerin trioleate (trade name: Sunsoft A-173E) as a polyglycerin fatty acid ester , HLB: 7, Taiyo Kagaku Co., Ltd.) 20 mg, fats and oils (trade name: Nisshin Canola Oil, long chain fatty acid triglyceride (LCT), Nisshin Oilio Group Co., Ltd.) 2 g, and bovine serum albumin (manufactured by SIGMA) 200 mg Were added, and the obtained solution was sonicated while cooling on ice (2 sets of 5 minutes, total 10 minutes) to obtain Sample 3.

  Seven-week-old SD male rats (purchased from Japan SLC) were used in the test. After the rats (17 rats) were acclimated for 1 week, a glucose tolerance test in which samples 1 and 3 were administered at 8 and 9 weeks of age was performed by the crossover method. Rearing conditions were the same as in Test Example 1.

  In the test, a “control trial (sample 1 administration trial)” in which fat and oil are administered at the same time as the sugar load, and trioleate pentaglycerin (HLB: 7), which is a fatty acid ester and polyglycerin fatty acid ester, are administered at the same time as the sugar load. This was performed in two trials, “Trioleic acid pentaglycerin (HLB: 7) administration trial (sample 3 administration trial)”. The sample administration method and dose were the same as in Test Example 1.

  Then, blood was collected from the tail vein before administration and 20 minutes after administration, and plasma insulin concentration (ng / ml) was measured in the same manner as in Test Example 1. The test results are shown in FIG. The plasma insulin concentration increase in the trial of trioleic acid pentaglycerin (HLB: 7) is a relative value (%) with the average value of the plasma insulin concentration increase in the control trial being 100, and the average value of the relative values ± Expressed in standard error. The Student t-test test was used for the significant difference test between trials, and it was judged that there was a significant difference with a risk rate of less than 5%.

  As shown in FIG. 1 (B), the plasma insulin concentration increase in the trial with trioleic acid pentaglycerin (HLB: 7) was significantly (P <0.01) higher than that in the control trial. From this, it became clear that according to pentaglycerin trioleate which is a polyglycerin fatty acid ester having an HLB value of 7, insulin secretion into plasma is promoted. In addition, the average value (absolute value) of the plasma insulin concentration increase in the control trial is 1.32 ± 0.14 ng / ml, and the average plasma insulin concentration increase in the trial treatment with pentaglycerin trioleate (HLB: 7) The value (absolute value) was 2.02 ± 0.20 ng / ml.

[Test Example 3] Examination of plasma insulin secretion promoting effect (3)
The effect of polyglycerin fatty acid ester on plasma insulin secretion was studied by administering fat or oil and fat and deglycerin acid decaglycerin (HLB: 3) simultaneously with glucose loading to rats. It was.

<Production example 4> Production method of sample 4 Dekaglycerin dekaleate (trade name: Sunsoft Q-1710S, HLB: 3, Taiyo) in 10 ml of 40% glucose (D (+)-Glucose, manufactured by Wako Pure Chemical Industries, Ltd.) solution 20 mg of oil and fat (trade name: Nisshin Canola Oil, long chain fatty acid triglyceride (LCT), Nisshin Oillio Group) 2 mg, and 200 mg of bovine serum albumin (manufactured by SIGMA) were obtained. The resulting solution was sonicated while cooling on ice (2 sets of 5 minutes, total 10 minutes) to obtain Sample 4.

  Seven-week-old SD male rats (purchased from Japan SLC) were used in the test. After the rats (10 rats) were acclimated for 1 week, a glucose tolerance test in which samples 1 and 4 were administered at 8 and 9 weeks of age was performed by the crossover method. Rearing conditions were the same as in Test Example 1.

  In the test, a “control trial (sample 1 administration trial)” in which fat and oil are administered simultaneously with the sugar load, and fat and fat and polyglycerin fatty acid ester decaglycerin (HLB: 3) are administered simultaneously with the sugar load. It was carried out in two trials, "Dekaleic acid decaglycerin (HLB: 3) administration trial (sample 4 administration trial)". The sample administration method and dose were the same as in Test Example 1.

  Then, blood was collected from the tail vein before administration and 20 minutes after administration, and plasma insulin concentration (ng / ml) was measured in the same manner as in Test Example 1. The test results are shown in FIG. The plasma insulin concentration increase in the trial of dekaleic acid decaglycerin (HLB: 3) is a relative value (%) where the average value of the plasma insulin concentration increase in the control trial is 100, and the average of the relative values ± standard Expressed in error. The Student t-test test was used for the significant difference test between trials, and it was judged that there was a significant difference with a risk rate of less than 5%.

  As shown in FIG. 2, the plasma insulin concentration in the dekaleic acid decaglycerin (HLB: 3) administration trial showed a lower value compared with the control trial, although no significant difference was observed. From this, it was clarified that decaglycerin dekaoleate (HLB: 3) has no action of promoting insulin secretion. In addition, the average value (absolute value) of the plasma insulin concentration increase in the control trial is 1.38 ± 0.16 ng / ml, and the average value of the plasma insulin concentration increase in the dekaleic acid decaglycerin (HLB: 3) administration trial The (absolute value) was 1.26 ± 0.13 ng / ml.

[Test Example 4] Examination of plasma insulin secretion promoting effect (4)
Examination of the effect of polyglycerin fatty acid ester on plasma insulin secretion by administering fat or oil and tetraglycerin monooleate (HLB: 8.8), which is a polyglycerin fatty acid ester, to rats simultaneously with sugar loading Went.

<Production Example 5> Production method of sample 5 Tetraglycerin monooleate (trade name: SY Glyster MO-3S) as a polyglycerol fatty acid ester in 10 ml of 40% glucose (D (+)-Glucose, manufactured by Wako Pure Chemical Industries, Ltd.) solution , HLB: 8.8, manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) 20 mg, fats and oils (trade name: Nisshin Canola Oil, long-chain fatty acid triglyceride (LCT), manufactured by Nisshin Oillio Group), bovine serum albumin (SIGMA) 200 mg was added, and the resulting solution was sonicated while cooling on ice (2 sets of 5 minutes, total 10 minutes) to obtain Sample 5.

  Seven-week-old SD male rats (purchased from Japan SLC) were used in the test. After the rats (17 animals) were acclimated for 1 week, a glucose tolerance test was performed by the crossover method in which samples 1 and 5 were administered at 8 and 9 weeks of age. Rearing conditions were the same as in Test Example 1.

  The test consists of administration of oil and fat at the same time as the sugar load, and administration of oil and fat and polyglycerol fatty acid ester monooleate tetraglycerin (HLB: 8.8) at the same time as the sugar load. The test was performed in two trials of “tetraglyceryl monooleate (HLB: 8.8) administration trial (sample 5 administration trial)”. The sample administration method and dose were the same as in Test Example 1.

  Then, blood was collected from the tail vein before administration and 20 minutes after administration, and plasma insulin concentration (ng / ml) was measured in the same manner as in Test Example 1. The test results are shown in FIG. The increase in plasma insulin concentration in the trial of administration of tetraglycerin monooleate (HLB: 8.8) is a relative value (%) where the average value of the increase in plasma insulin concentration in the control trial is 100, and the average of the relative values. It was expressed as a value ± standard error. The Student t-test test was used for the significant difference test between trials, and it was judged that there was a significant difference with a risk rate of less than 5%.

  As shown in FIG. 3, the plasma insulin concentration increase in the trial of administration of tetraglyceryl monooleate (HLB: 8.8) was significantly higher (P <0.01) than in the control trial. From this, it became clear that insulin secretion into plasma is promoted according to tetraglyceryl monooleate, which is a polyglycerin fatty acid ester having an HLB value of 8.8. In addition, the average value (absolute value) of the plasma insulin concentration increase in the control trial is 0.71 ± 0.06 ng / ml, and the plasma insulin concentration increase in the monooleate tetraglycerin (HLB: 8.8) administration trial The average value (absolute value) was 1.35 ± 0.20 ng / ml.

Claims (4)

Oral insulin secretagogue agent characterized by containing the polyglycerol fatty acid ester of HLB4～ 9 as an active ingredient. The insulin secretion promoter for oral administration according to claim 1, comprising the polyglycerin fatty acid ester together with fats and oils. The insulin secretion promoter for oral administration according to claim 1, which is used in combination with fats and oils. The insulin secretion promoter for oral administration according to any one of claims 1 to 3, which is used for prevention or treatment of type II diabetes.

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