HK1168793B

HK1168793B - Glucose metabolism-improving agent and glucose metabolism-improving composition

Info

Publication number: HK1168793B
Application number: HK12109609.0A
Authority: HK
Inventors: Iwasaki Hideaki; Kambayashi Hiroaki; Nomura Mitsuru; Suzuki Naho; Kitamura Kumiko
Original assignee: Lion Corporation
Priority date: 2009-06-30
Filing date: 2010-06-30
Publication date: 2014-01-24

Description

Sugar metabolism-improving agent and sugar metabolism-improving composition

Technical Field

The present invention relates to a sugar metabolism-improving agent comprising at least one of Panaxatriol (PT) and Panaxadiol (PD), and a sugar metabolism-improving composition containing the sugar metabolism-improving agent.

Background

It is presumed that about 820 million people exist in diabetic patients in China and about 1050 million people exist in diabetic preparation armies, and the number of the patients is increasing year by year. Japanese belongs to the constitution of easy-to-obtain diabetes, namely belongs to the constitution of difficult consumption and easy storage of food, and the retention rate of the frugal gene ( Orn) is said to be 2-5 times of that of European and American people. Therefore, the prevention and treatment of diabetes become important problems.

The disease classification of diabetes can be classified into 3 types (Japanese diabetes society guidelines) of normal type, borderline type and diabetes type, and the diabetes preparation refers to borderline type patients.

The criteria for determining the type of diabetes are set as follows: (1) a fasting blood glucose level of 126mg/dL or more, (2) a postprandial blood glucose level of 200mg/dL or more, (3) a blood glucose level of 200mg/dL or more after 2 hours in a 75g glucose tolerance test, (4) typical symptoms of diabetes (thirst, polydipsia, polyuria, weight loss, etc.), (5) HbA1c (glycated hemoglobin) of 6.5 mass% or more, and (6) a standard for a definite diabetic retinopathy or the like.

The above-mentioned critical type is in accordance with (1) a condition that the fasting blood glucose value is 110mg/dL or more and less than 126mg/dL, and (2) a condition that the blood glucose value is 140mg/dL or more and less than 200mg/dL after 2 hours in a 75g glucose tolerance test.

Currently, diabetes therapeutic agents include sulfonylurea agents (SU agents) that promote insulin secretion, phenylalanine derivatives, α -glucosidase inhibitors that inhibit sugar absorption, biguanide agents (BG) that inhibit sugar production in the liver, thiazolidine derivatives that improve insulin resistance, and the like, but these agents have little effect of regulating both fasting blood glucose and postprandial blood glucose. In addition, these drugs can be administered only when diabetes is diagnosed, and patients who are borderline type are only dependent on food therapy and exercise therapy to prevent the development of diabetes.

In addition, improvement of hyperglycemia due to diabetes is expected to be a non-temporary, fundamental improvement including physical constitution. Excess glucose taken up in the body enters the liver and muscles from the blood and is stored as glycogen. It is presumed that if the synthesis of glycogen is promoted, the hyperglycemia state is improved. Since sugar metabolism of 70% or more proceeds in the muscle, it is expected that the hyperglycemia state is improved by promoting glucose entry into the muscle.

In order to maintain such a constitution that sugar metabolism is actively performed in muscles, not only the above-mentioned agents but also diabetes improvement by food therapy is effective. In addition to the above drugs, there are many substances that can be ingested as foods to suppress the postprandial blood glucose level, but there are only drugs that suppress the fasting blood glucose level, and it is desired to provide foods that suppress the fasting blood glucose level.

Glycosides (ginsenosides) contained in ginseng are known to have a blood glucose level regulating effect (see patent document 1) and an antidiabetic effect (see patent document 2), and glycoside aglycons (aglycons) of ginseng triol (PPT) and protopanaxadiol (PPD) in which glycosyl groups are removed from the glycosides have various effects such as an anticancer effect (see patent documents 3 to 4), an anti-inflammatory effect against skin diseases (see patent document 5), an activation effect of PPAR γ that regulates expression of important genes of fat metabolism and sugar metabolism (see patent document 6), and an inhibitory effect of synthesis of Heat Shock Protein (HSP) involved in autoimmune diseases (see patent document 7).

The protopanaxatriol (PPT) and protopanaxadiol (PPD) are white powders, insoluble in water, but the solubility can be improved by adding an organic solvent. However, the above protopanaxatriol (PPT) and protopanaxadiol (PPD) are unstable in structure and rapidly decompose in a solution, particularly in a low pH environment. Further, there is a problem that even in the powder state, decomposition proceeds on a daily basis under the temperature condition of room temperature or more.

Therefore, at present, it is desired to rapidly provide a compound having a blood glucose level regulating action and a sugar metabolism improving action, having high safety, being ingestible as a food or drink, and having high stability.

Prior Art

Patent document

Patent document 1: japanese patent laid-open publication No. 2008-533132

Patent document 2: japanese patent laid-open No. 61-24547

Patent document 3: japanese patent laid-open publication No. 2005-504799

Patent document 4: japanese patent laid-open No. 58-57399

Patent document 5: japanese patent laid-open No. 2007-008896

Patent document 6: korean laid-open patent No. 10-2006-0131012

Patent document 7: japanese patent laid-open No. 9-241166

Disclosure of Invention

Problems to be solved by the invention

The present invention has been made to solve the above-described problems, and an object of the present invention is to achieve the following object. That is, an object of the present invention is to provide a glycometabolism improving agent which has an excellent blood glucose level regulating effect and a glycometabolism improving effect, is highly safe and can be ingested as a food or beverage, and has high stability, and a glycometabolism improving composition containing the glycometabolism improving agent.

Means for solving the problems

The present inventors have made extensive studies to solve the above problems, and as a result, have obtained the following knowledge. That is, the present inventors have found that a sugar metabolism improving agent comprising at least one of Panaxatriol (PT) and Panaxadiol (PD) has an inhibitory action on the promotion of sugar entry into muscle cells and postprandial increase in blood glucose level, an action of lowering fasting blood glucose level, an action of regulating an index relating to sugar metabolism, and an action of promoting the metabolism of sugar derived from food, and have completed the present invention.

The present invention is based on the above knowledge of the present inventors, and means for solving the above problems are as follows. That is to say that the first and second electrodes,

<1> a sugar metabolism-improving agent characterized by comprising at least one of a compound represented by the following structural formula (1) and a compound represented by the following structural formula (2).

[ solution 1]

Structural formula (1)

[ solution 2]

Structural formula (2)

<2> the sugar metabolism-improving agent according to <1> above, which has an effect of inhibiting an increase in postprandial blood glucose level.

<3> the sugar metabolism-improving agent according to any one of <1> to <2> above, which has at least one of a lowering action of fasting blood sugar level and a regulating action of serum sugar metabolism-related index.

<4> the sugar metabolism-improving agent according to any one of <1> to <3> above, which has an action of promoting the metabolism of sugar derived from food.

<5> the sugar metabolism-improving agent according to any one of <1> to <4> above, which has an action of promoting entry of sugar into muscle cells.

<6> the sugar metabolism-improving agent according to any one of <1> to <5> above, which exerts a sugar metabolism-improving effect without being taken together with food.

<7> the sugar metabolism-improving agent according to any one of <1> to <6> above, wherein the daily intake amount is at least 1 mg.

<8> a sugar metabolism-improving composition comprising the sugar metabolism-improving agent according to any one of <1> to <7 >.

<9> an inhibitor for postprandial increase in blood glucose level, which comprises the sugar metabolism-improving agent according to any one of <1> to <7 >.

<10> an agent for reducing fasting blood glucose level, which comprises the sugar metabolism-improving agent according to any one of <1> to <7 >.

<11> an agent for promoting sugar entry into muscle cells, which comprises the sugar metabolism-improving agent as described in any one of <1> to <7 >.

<12> A food or beverage characterized by containing the sugar metabolism-improving agent according to any one of <1> to <7 >.

Effects of the invention

The present invention solves the above-described problems, and provides a glucose metabolism improving agent having excellent blood glucose level regulating activity and glucose metabolism improving activity, high safety, high stability, and capability of being ingested as a food or beverage, and a glucose metabolism improving composition containing the glucose metabolism improving agent.

Drawings

FIG. 1 is a graph showing the change in fasting blood glucose value in the PT intake human test of example 5. The vertical axis represents blood glucose level (mg/dL), and the horizontal axis represents elapsed days after the start of PT intake.

FIG. 2 is a graph showing the change in postprandial blood glucose values in placebo (placebo) intake group of PT intake human trial of example 5. The vertical axis represents the blood glucose level (mg/dL), and the horizontal axis represents the elapsed time (minutes) after a meal.

FIG. 3 is a graph showing the change in postprandial blood glucose values in the Panaxatriol (PT) intake group of the human test with PT intake in example 5. The vertical axis represents the blood glucose level (mg/dL), and the horizontal axis represents the elapsed time (minutes) after a meal.

FIG. 4 is a graph showing the change in fasting blood glucose value in the PD uptake human test of example 6. The vertical axis represents blood glucose level (mg/dL), and the horizontal axis represents the number of days elapsed after the start of PD ingestion.

FIG. 5 is a graph showing the change in postprandial blood glucose values in the placebo (placebo) intake group of the PD intake human trial of example 6. The vertical axis represents the blood glucose level (mg/dL), and the horizontal axis represents the elapsed time (minutes) after a meal.

FIG. 6 is a graph showing the change in postprandial blood glucose values in the Panaxadiol (PD) intake group of the human test with PD intake of example 6. The vertical axis represents the blood glucose level (mg/dL), and the horizontal axis represents the elapsed time (minutes) after a meal.

[ FIG. 7A)]FIG. 7A shows groups of example 7¹³CO₂A graph of the change with time of the discharge amount. The vertical axis represents in the expired air¹³CO₂Output (% by volume), horizontal axis represents administration of glucose-U-¹³C₆The latter time (minutes).

[ FIG. 7B]FIG. 7B is a view showing the accumulation of the groups of example 7¹³CO₂A graph of discharge volume. The vertical axis represents AUC: (¹³CO₂Discharge amount increase value).

Detailed Description

(sugar metabolism improvers)

The sugar metabolism-improving agent of the present invention is composed of at least one of a compound represented by the following structural formula (1) and a compound represented by the following structural formula (2).

[ solution 3]

Structural formula (1)

[ solution 4]

Structural formula (2)

< Compound represented by the structural formula (1) and Compound represented by the structural formula (2) >

The compound represented by the structural formula (1) belongs to Dammarane (Dammarane) triterpenes (tripterpene) compounds. Hereinafter, it may be referred to as "Panaxatriol (PT)". In addition, the compound represented by the structural formula (2) belongs to dammarane triterpenes. Hereinafter, it may be referred to as "Panaxadiol (PD)".

The Panaxatriol (PT) and the Panaxadiol (PD) are aglycones (aglycones) obtained by removing a sugar group from a plant-derived saponin (glycoside) and closing a side chain.

-method of acquisition-

The method for obtaining the Panaxatriol (PT) and the Panaxadiol (PD) is not particularly limited, and may be appropriately selected according to the purpose, and examples thereof include a method of purchasing a commercially available product, a method of obtaining them by synthesis, and a method of obtaining them from the plant.

The plant is not particularly limited and may be appropriately selected according to the purpose, and preferably, it is Panax ginseng C.A.Meyer of Araliaceae (Araliaceae), and more preferably, Panax notoginseng.

The saponin (saponin) derived from panax notoginseng is not particularly limited, and may be appropriately selected according to the purpose, and examples thereof include: ginsenoside-Rg₁(Ginsenoside-Rg₁) notoginsenoside-R₁(Notoginsenoside-R₁) ginsenoside-Re and ginsenoside-Rb₁ginsenoside-Rd, ginsenoside-Rc, etc.

Hereinafter, an example of a method for obtaining Panaxatriol (PT) and Panaxadiol (PD) from a ginseng belonging to the family araliaceae will be described. The method for obtaining the Panaxatriol (PT) and Panaxadiol (PD) from the ginseng belonging to the family araliaceae is not particularly limited, and may be appropriately selected according to the purpose, for example, a method of extraction and/or purification from ginseng belonging to the family araliaceae.

The method for obtaining the notoginseng powder by extraction is not particularly limited, and may be appropriately selected according to the purpose, for example, a method for obtaining the notoginseng powder by extraction with a water-ethanol solution, and the like.

The mixing ratio of the water-ethanol solution is not particularly limited and may be appropriately selected according to the purpose, but the ratio of water to ethanol (V/V) is preferably 9: 1 to 2: 1, and more preferably 3: 1.

In the extraction, a method of adding hydrochloric acid to the aqueous-ethanol solution and performing acid hydrolysis is preferable from the viewpoint that at least one of the Panaxatriol (PT) and the Panaxadiol (PD) can be obtained at a high concentration. The concentration of the hydrochloric acid is not particularly limited and may be appropriately selected according to the purpose, but is preferably 0.04 to 16% by mass, and more preferably 2 to 12% by mass.

The temperature of the acid hydrolysis is not particularly limited and may be appropriately selected depending on the purpose, but is preferably 60 to 100 ℃, and more preferably 70 to 90 ℃.

The time for the acid hydrolysis is not particularly limited and may be appropriately selected depending on the purpose, but is preferably 0.5 to 24 hours, and more preferably 2 to 8 hours.

The panax notoginseng hydrolysate obtained by the acid hydrolysis may be neutralized with caustic soda, if necessary, after reducing the ethanol concentration, filtered by suction or other methods, and then the residue may be subjected to drying treatment such as lyophilization, drying under reduced pressure, or spray drying, whereby at least one of the Panaxatriol (PT) and Panaxadiol (PD) derived from panax notoginseng can be obtained.

The method for obtaining the above-mentioned by purification is not particularly limited, and may be appropriately selected according to the purpose, for example, a method of purification using a silica gel column.

The method of purification using a silica gel column is not particularly limited, and may be appropriately selected according to the purpose, and for example, a method of preparing an ethanol solution containing 1 to 5 mass% of the treated product obtained by hydrolysis by adding an acid, removing insoluble substances by a filter paper or a centrifuge, concentrating 5 to 10 times by using a rotary evaporator, adding the concentrated solution to a glass column packed with silica gel (for example, silica gel 60N produced by kanto chemical corporation), and performing column separation using chloroform/ethanol of 10: 1(V/V) as an eluent.

High-purity Panaxatriol (PT) can be obtained by concentrating a portion of the normal-phase TLC in which chloroform and ethanol are used as a developing solvent at a ratio of 10: 1(V/V) and Rf is 0.4. Similarly, a high-purity Panaxadiol (PD) was obtained by concentrating a portion of the normal-phase TLC in which chloroform and ethanol were used as developing solvents at a ratio of 10: 1(V/V) and Rf was 0.6.

< intake >

The method of taking the sugar metabolism-improving agent, the amount of taking, the number of times of taking, the time of taking, and the subject of taking are not particularly limited, and may be appropriately selected depending on the purpose.

The method of taking is not particularly limited and may be appropriately selected depending on the purpose, but a method of taking orally is preferable from the viewpoint of easy maintenance because it enables easy taking.

The amount to be taken is not particularly limited, and may be appropriately selected in consideration of various factors depending on the age, body weight, body constitution, symptoms of the subject to be taken, the presence or absence of administration of a drug containing other components as active ingredients, and the like, but the amount to be taken per day is preferably at least 1mg, more preferably 2mg to 20 mg. Within the above preferred range, it is advantageous from the viewpoint of suppressing both postprandial blood glucose level and fasting blood glucose level and improving ease of administration.

The number of times of ingestion is not particularly limited and may be appropriately selected according to the purpose, but from the viewpoint of convenience, 1 time per day is preferred.

The intake time is not particularly limited and may be appropriately selected according to the purpose. In order to reduce the inconvenience of taking by the user, it is preferable that the intake time should not be limited to the intake time at the same time as the meal or after the meal, and that the glucose metabolism-improving effect is exhibited even if the intake is not performed at the same time as the meal.

The species of the animal to be ingested is preferably human, but animals other than human (for example, mouse, rat, hamster, bird, dog, cat, sheep, goat, cow, pig, monkey, etc.) may be used as long as they exert their effects.

< sugar metabolism-improving action >

The sugar metabolism-improving action of the sugar metabolism-improving agent is not particularly limited and may be appropriately selected depending on the purpose, but preferably has at least one of a postprandial increase-suppressing action of blood glucose level, a fasting blood glucose level-lowering action, and a food-derived sugar metabolism-promoting action based on a sugar entry-promoting action into cells.

Sugar entry into cells

The cell is not particularly limited and may be appropriately selected according to the purpose, and examples thereof include muscle cells, liver cells, fat cells, and the like, and among them, muscle cells are preferable. Since the muscle cells are cells that are responsible for 70% or more of sugar metabolism, they are expected to function efficiently as sugar-entering organs. On the other hand, since the liver and fat cells are at risk of developing fatty liver and obesity symptoms, it is preferable to use muscle cells as a subject of sugar entry if possible, although improvement of the hyperglycemic state is expected.

Although the details of the mechanism of action of the sugar entry promoting action are not clear, it is presumed that the sugar metabolism-improving agent promotes translocation of GLUT4, which is present locally in the cell, to the cell membrane.

Evaluation of sugar entry promoting action- -

The method for evaluating the sugar-uptake promoting effect is not particularly limited, and may be appropriately selected depending on the purpose, for example, a method in which the sugar metabolism improving agent is added to a medium of cultured cells to induce sensitization (sensitization) for a certain period of time, and then labeled sugar is added to the medium, the cultured cells are lysed, and the label in the cultured cells is measured.

The cultured cells are not particularly limited and may be appropriately selected according to the purpose, and for example, L6 cells derived from rat skeletal muscle cells, C2C12 cells derived from mouse skeletal muscle cells, and the like may be used.

1. The medium for culturing the L6 cells is not particularly limited, and may be appropriately selected according to the purpose, and examples thereof include DMEM (Dulbecco's modified Eagle medium) containing 10 mass% FBS (fetal bovine serum) and 1 mass% AB (anti-biological solution), and the like. The method for inducing differentiation of the L6 cells is not particularly limited, and may be appropriately selected according to the purpose, and for example, the method may be performed by culturing in MEM containing 2 mass% FBS and 1 mass% AB.

The labeling substance for the saccharide is not particularly limited and may be appropriately selected according to the purpose, and examples thereof include RI labeling substances and the like. The method of introducing the above RI-labeled sugar is not particularly limited, and may be appropriately selected according to the purpose, for example, a method of adding the RI-labeled sugar to a medium. The sugar is not particularly limited and may be appropriately selected according to the purpose, and examples thereof include glucose and the like.

The method for lysing the cells is not particularly limited, and may be appropriately selected according to the purpose, and for example, a method using 0.05N sodium hydroxide is used.

The method for measuring the radioactivity of the saccharide is not particularly limited if the saccharide is an RI label, and may be appropriately selected according to the purpose, for example, a method of adding a Scintillation cocktail (Scintillation cocktail) Picoflour (Perkin Elmer Co.) to a vial from which the lysed cells are collected, or a method of measuring the radioactivity using a Scintillation cocktail.

Postprandial blood glucose values-

The postprandial blood glucose level is a blood glucose level 30 to 120 minutes after a meal.

The postprandial blood glucose level may be appropriately selected depending on the age, elapsed time after a meal, etc., but is preferably less than 180mg/dL in the case of 30 minutes after a meal and less than 140mg/dL in the case of 120 minutes after a meal in a human.

Evaluation method of postprandial blood glucose level-

The method for evaluating postprandial blood glucose level is not particularly limited, and may be appropriately selected depending on the purpose, and examples thereof include a method for evaluating a hyperglycemic model mouse, and a method for evaluating a starch-loaded food for human.

The method of measuring the blood glucose level is not particularly limited, and may be appropriately selected depending on the purpose, and examples thereof include a method of measuring with a simple blood glucose meter (for example, Free style manufactured by Nipro corporation), and a method of measuring with a rotary GB Sensor (manufactured by Cydic GB Sensor, Sanko pure chemical industries, Ltd.).

Evaluation method based on hyperglycemic model mice

The method of evaluating mice based on a hyperglycemic model is not particularly limited, and may be appropriately selected depending on the purpose, for example, a method of feeding a high-fat diet mixed with the above-mentioned glucose metabolism-improving agent for a certain period of time and measuring the blood glucose level after feeding.

The hyperglycemia model mouse is not particularly limited, and may be appropriately selected according to the purpose, and examples thereof include KKAy mice (japanese clean corporation) and ZDF rats (japanese Charles River corporation).

The high-Fat food is not particularly limited and may be appropriately selected according to the purpose, and for example, a commercially available product (Quick Fat, manufactured by japanese clean corporation) or the like may be used.

The feeding time is not particularly limited, and may be appropriately selected according to the purpose, for example, 4 to 35 days.

Evaluation of human starch-loaded foods

The method for evaluating the human starch-loaded diet is not particularly limited, and may be appropriately selected depending on the purpose, for example, a method in which a subject having a high fasting blood glucose value (120mg/dL to 140mg/dL) takes a predetermined diet for a certain test period, takes the glucose metabolism-improving agent 1 time a day for 1 day during a period of time in which the subject does not take the diet at the same time, and measures the change in blood glucose level every 30 minutes to 120 minutes after a meal.

The test period is not particularly limited, and may be appropriately selected according to the purpose, for example, 4 weeks to 16 weeks.

The food to be specified is not particularly limited and may be appropriately selected according to the purpose, but is preferably a food having a large starch content such as rice and pasta.

Fasting blood glucose level-

The fasting blood glucose value is a blood glucose value of blood collected in the morning after getting up and fasting. Further, the blood glucose level measured from blood collected at intervals of 10 hours or more after a meal is more stringent.

The fasting blood glucose level may be appropriately selected depending on age, etc., but is preferably less than 110mg/dL for human.

Evaluation method of fasting blood glucose level-

The method for evaluating the fasting blood glucose level is not particularly limited, and may be appropriately selected according to the purpose, and for example, the evaluation may be performed by the same method as the above-described method for evaluating a human-load starchy food, in addition to the method for measuring the fasting blood glucose level.

-sugar metabolism-related index-

The sugar metabolism-related index is not particularly limited, and may be appropriately selected according to the purpose, for example, a blood index.

The blood index is not particularly limited, and may be appropriately selected according to the purpose, and examples thereof include HbA1c (glycated hemoglobin), glycated albumin, 1.5 AG (1, 5-anhydroglucitol), and insulin.

The method of measuring the blood index is not particularly limited, and may be appropriately selected according to the purpose, and for example, the blood index may be measured according to a method conventionally used in medical institutions using blood collected in the above-described evaluation test for starch-loaded foods for humans.

--HbA1c--

The HbA1c (glycated hemoglobin) is a substance in which hemoglobin (Hb) in red blood cells is bound to glucose. That is, if the blood glucose level increases, the HbA1c value increases. Since the reaction rate of the hemoglobin (Hb) to glucose is slow, this value is not affected by physiological conditions for a while, and reflects the average blood glucose of the past 1 month to 2 months.

The normal value of HbA1c is 4.3 to 5.8% by mass, and if it is 6.5% by mass or more, the probability of diabetes becomes extremely high.

Glycated Albumin- -

The glycated albumin is a substance in which albumin in blood is bound to glucose. That is, if the blood glucose level increases, the value of glycated albumin increases.

Since the glycated albumin has a shorter half-life than HbA1c, it reflects a recent past average blood glucose, i.e., an average blood glucose before 1 to 2 weeks, compared to HbA1 c.

The normal value of the glycated albumin is 11.6 to 16.4% by mass.

--1·5AG--

The above-mentioned 1.5 AG is a polyol having a structure similar to that of glucose, and is abundantly present in the body. The 1.5 AG is supplied with food, and the excess 1.5 AG is excreted into urine. Normally, the 1.5 AG undergoes tubular reabsorption, but if glucose is excreted (urine glucose) with hyperglycemia, reabsorption of the 1.5 AG is competitively inhibited and the concentration in blood decreases because the 1.5 AG is lost to urine. As described above, 1.5 AG is increased or decreased by the influence of urine glucose, and therefore, it is now or recently used as an index of blood glucose.

However, if the HbA1c level is 10% by mass or more, 1.5 AG is discharged to the outside of the body, and therefore, the HbA1c is suitable as an index in this case.

The normal value of 1.5 AG is 14. mu.g/mL-46. mu.g/mL.

Sugar metabolism promoting action from food

The sugar derived from food is not particularly limited and may be appropriately selected according to the purpose, and examples thereof include sucrose, maltose, lactose, glucose, fructose, galactose and the like.

The method for evaluating the sugar metabolism promoting effect is not particularly limited, and may be appropriately selected depending on the purpose, for example, a method for measuring the carbon dioxide emission amount.

< use >

The glucose metabolism-improving agent is excellent in the effect of inhibiting the increase in postprandial blood glucose level, the effect of reducing fasting blood glucose level, the effect of regulating glucose metabolism-related markers, the effect of promoting the entry of sugar into muscle cells, and the effect of promoting the metabolism of sugar derived from food, and therefore can be suitably used in a glucose metabolism-improving composition, a postprandial blood glucose level increase inhibitor, a fasting blood glucose level-reducing agent, and a sugar entry-promoting agent, which will be described later.

(composition for improving sugar metabolism)

The sugar metabolism-improving composition of the present invention contains the sugar metabolism-improving agent and, if necessary, other components.

The content of the sugar metabolism-improving agent in the sugar metabolism-improving composition is not particularly limited, and may be appropriately selected according to the purpose. Further, the sugar metabolism-improving composition may be the sugar metabolism-improving agent itself.

Other components of the sugar metabolism-improving composition are not particularly limited, and may be appropriately selected depending on the purpose within the range not impairing the effect of the present invention, for example, pharmacologically acceptable carriers such as ethanol, water and starch, or auxiliary materials or additives used in foods and beverages described later.

The content of the other components is not particularly limited and may be appropriately selected according to the purpose.

< use >

The sugar metabolism improving composition may be used alone in 1 kind, or in combination of 2 or more kinds, and may be used in combination with other medicines containing other components as effective components. The sugar metabolism-improving composition may be used in a state of being mixed with a pharmaceutical product containing other components as active ingredients.

< use >

The use of the sugar metabolism improving composition can be suitably used for the prevention or treatment of diabetes, for example. The present invention can be applied to foods and beverages described later.

(inhibitor of postprandial increase in blood sugar level, agent for lowering fasting blood sugar level, and agent for promoting sugar entry)

< inhibitor of postprandial increase in blood glucose level >

The inhibitor for postprandial increase in blood glucose level of the present invention contains the above-mentioned sugar metabolism-improving agent and, if necessary, further contains other components.

The content of the glucose metabolism-improving agent in the inhibitor for postprandial increase in blood glucose level is not particularly limited and may be appropriately selected according to the purpose. The postprandial increase in blood glucose level inhibitor may be the sugar metabolism improver itself.

The other components of the inhibitor for postprandial increase in blood glucose level are not particularly limited and may be appropriately selected depending on the purpose, for example, from pharmacologically acceptable carriers such as ethanol, water and starch according to the dosage form of the inhibitor for postprandial increase in blood glucose level.

< agent for reducing fasting glucose level >

The fasting blood glucose level lowering agent of the present invention contains the glucose metabolism-improving agent and, if necessary, further contains other components.

The content of the glucose metabolism-improving agent in the fasting blood glucose level-lowering agent is not particularly limited, and may be appropriately selected according to the purpose. The fasting blood glucose level lowering agent may be the glucose metabolism-improving agent itself.

The other components of the fasting blood glucose level lowering agent are not particularly limited and may be appropriately selected depending on the purpose, and for example, may be appropriately selected from pharmacologically acceptable carriers such as ethanol, water, starch and the like according to the form of the preparation of the fasting blood glucose level lowering agent and the like.

< sugar entry promoters >

The sugar entry accelerator of the present invention contains the sugar metabolism improver and, if necessary, further contains other components.

The content of the sugar metabolism-improving agent in the sugar entry-promoting agent is not particularly limited and may be appropriately selected according to the purpose. Further, the sugar entry-promoting agent may be the sugar metabolism-improving agent itself.

The other components of the sugar entry enhancer are not particularly limited and may be appropriately selected depending on the purpose, for example, from pharmacologically acceptable carriers such as ethanol, water, and starch in accordance with the dosage form of the sugar entry enhancer.

< use >

The inhibitor of postprandial increase in blood glucose level, the agent of lowering fasting blood glucose level and the agent of promoting glucose entry may be used alone in 1 kind, or in combination with 2 or more kinds, or may be used in combination with a drug containing other components as active ingredients. The inhibitor for postprandial increase in blood glucose level, the agent for lowering fasting blood glucose level, and the agent for promoting entry of sugar may be used in the form of a mixture with a pharmaceutical preparation containing another component as an active ingredient.

< use >

The use of the inhibitor for postprandial increase in blood glucose level, the agent for lowering fasting blood glucose level, and the agent for promoting entry of sugar can be suitably used for the prevention or treatment of diabetes, for example. The present invention can be applied to foods and beverages described later.

(drinks and foods)

The food or drink of the present invention contains the sugar metabolism-improving agent and, if necessary, further contains other components.

Here, the food or drink is an article which is less likely to be harmful to human health, and in general social life, taken through the mouth or through the digestive tract is not limited by the classification of food, medicine, quasi-medicine, and the like in administrative classification, and includes, for example, general food, health functional food, quasi-medicine, and the like taken through the mouth.

The content of the sugar metabolism-improving agent in the food or drink is not particularly limited, and may be appropriately selected depending on the type of the food or drink to be served, within a range not impairing the effect of the present invention.

The food or drink may contain only the sugar metabolism-improving agent, or the food or drink may be the sugar metabolism-improving agent itself.

< types of foods and beverages >

The type of the food or drink is not particularly limited, and may be appropriately selected according to the purpose, and examples thereof include beverages such as soft drinks (soft drinks), carbonated beverages, nutritional beverages, fruit beverages, and lactic acid beverages; frozen desserts such as ice cream, water ice (ice sherbet), water ice, and the like; buckwheat flour, udon flour, vermicelli, dumpling wrapper, shaomai wrapper, Chinese style noodles, instant noodles, etc.; confectionery such as maltose, candy (candy), chewing gum, chocolate, candy slice (fudge), snack (スナツク seed), biscuit, jelly, jam, cream, baked snack, and bread; aquatic products such as crab, salmon, little clam, tuna, sardine, shrimp, bonito, mackerel, whale, oyster, saury, cuttlefish, blood clam, scallop, abalone, sea urchin, salmon roe, and abalone; processed food of aquatic products and livestock products such as fish cake, ham, sausage, etc.; processed milk, fermented milk, and other dairy products; oils and processed foods such as salad oil, tempura oil, margarine (margarine), mayonnaise, shortening, whipped cream (whip cream), and dressing (dressing); seasonings such as sauce (sauce) and seasoning for barbecue (たれ); curry, stewed dish, chicken and egg rice, porridge, vegetable porridge, Chinese rice covered with rice, pork chop rice covered with rice, fried shrimp bowl rice covered with rice, eel rice covered with rice, beef diced rice, guandong boiled rice, spicy bean curd, beef rice covered with rice, meat paste, egg soup, egg rice, dumpling, shaomai, hamburger, meatball, etc. in sealed bag (retro pouchh); health food, nutritional supplement food, medicine, quasi-medicine, etc. in various forms.

< other ingredients >

The other components of the food or drink are not particularly limited and may be appropriately selected according to the purpose, for example, auxiliary materials or additives usually used in the production of food or drink.

The auxiliary materials or additives are not particularly limited and may be appropriately selected according to the purpose, and examples thereof include glucose, fructose, sucrose, maltose, sorbitol, stevioside (stevioside), rubusoside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl- α -tocopherol, sodium erythorbate, glycerol, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin B, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, preservatives, and the like.

Examples

The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 blood sugar level lowering action in hyperglycemia model mice based on PT Mixed feed

< method >

Commercially available high-fat foods (trade name: QuickFat, manufactured by japan clean corporation) were fed to hyperglycemic model mice (KKAy mice (japan clean corporation) 8 weeks old, 5 mice/group) for 5 days (hereinafter, sometimes referred to as "mixed PT group") by a free-ingestion method using a feed mixed with Panaxatriol (PT) (manufactured by LKT Laboratories) at a ratio shown in table 1 below. For the control group (control), a feed not mixed with Panaxatriol (PT) (hereinafter, sometimes referred to as "unmixed PT group") was used

Blood glucose levels were measured at 10 am before (initial) and after (post-feeding) the start of feeding the high-fat diet mixed with Panaxatriol (PT). The blood glucose level was measured by rotating a GB Sensor (Cyclic GB Sensor; available from Sanko pure chemical industries, Ltd.). The average value of 2 measurements is shown in table 1 below as the postprandial blood glucose level for each individual. In addition, statistical analysis was performed according to the Dunnett's multiple test.

[ Table 1]

P＜01，*：P＜0.05，**：P＜0.01

< results >

According to table 1, in the group not mixed with PT (control group), a significant postprandial increase in blood glucose level was observed for 5 days when the initial value was compared with the value after 5 days of feeding. On the other hand, in the group administered with 0.0001 mass% PT, the increase in postprandial blood glucose level was significantly suppressed at a risk level of less than 10% as compared with the group not administered with PT (control group), in the group administered with 0.001 mass% PT, the increase in postprandial blood glucose level was significantly suppressed at a risk level of less than 5% as compared with the group not administered with PT (control group), and in the group administered with 0.01 mass% PT, the increase in postprandial blood glucose level was significantly suppressed at a risk level of less than 1% as compared with the group not administered with PT (control group).

From the above results, it was found that the KKAy mice mixed with PT in an amount of 0.0001% by mass or more had an effect of inhibiting the increase of postprandial blood glucose level.

Example 2 blood sugar level lowering action in hyperglycemia model mice based on PD Mixed feed

< method >

Commercially available high-fat foods (trade name: QuickFat, manufactured by japan clean corporation) were fed to hyperglycemic model mice (KKAy mice (japan clean corporation) 8 weeks old, 5 mice/group) for 5 days (hereinafter, sometimes referred to as "mixed PD group") by a free-ingestion method using a feed mixed with Panaxadiol (PD) (manufactured by LKT Laboratories) at a ratio shown in table 2 below. For the control group (control), a feed not mixed with Panaxadiol (PD) (hereinafter, sometimes referred to as "non-mixed PD group")

Blood glucose levels were measured at 10 am before (initial) and after (post-feeding) the start of feeding with the high-fat diet mixed with Panaxadiol (PD). The blood glucose level was measured by rotating a GB Sensor (Cyclic GB Sensor) (manufactured by sanko pure chemical industries, ltd.). The average value of 2 measurements is shown in table 2 below as the postprandial blood glucose level for each individual. In addition, statistical analysis was performed according to the Dunnett's multiple test.

[ Table 2]

P＜0.1，*：P＜0.05，**：P＜0.01

< results >

According to Table 2, in the group without mixed PD (control group), a significant postprandial increase in blood glucose level was observed for 5 days when the initial value was compared with the value after 5 days of feeding. On the other hand, in the group administered with 0.0001 mass% PD, the increase in postprandial blood glucose level was significantly suppressed at a risk level of less than 10% as compared with the group not administered with PD (control group), in the group administered with 0.001 mass% PD, the increase in postprandial blood glucose level was significantly suppressed at a risk level of less than 5% as compared with the group not administered with PD (control group), and in the group administered with 0.01 mass% PD, the increase in postprandial blood glucose level was significantly suppressed at a risk level of less than 1% as compared with the group not administered with PD (control group).

From the above results, it was found that KKAy mice mixed with 0.0001 mass% or more of PD had an effect of inhibiting postprandial increase in blood glucose level.

(example 3 promotion of sugar entry into cells from rat skeletal muscle based on addition of PT)

< method >

Rat skeletal muscle-derived cells (L6 cells, manufactured by Dainippon pharmaceutical Co., Ltd.) were suspended in 15mL of DMEM (Dulbecco's modified Eagle medium, manufactured by SIGMA) containing 10 mass% of FBS (total bone serum, manufactured by GIBCO Co., Ltd.) and 1 mass% of AB (anti-biological solution, manufactured by SIGMA Co., Ltd.), and injected into 75cm of DMEM²After in the flask, 5% CO at 37 ℃₂The culture is performed under static conditions. After reaching sub-confluency (80%), 50000 cells/well were seeded on a 24-well plate (well plate) (Sumitomo Bakelite Co., Ltd.). After culturing for 3 days from the time of reaching confluency (confluency), MEM (minimum essential medium) containing 2 mass% FBS and 1 mass% AB was changed to induce differentiation of L6 cells. After inducing differentiation for 8 days, Panaxatriol (PT) (manufactured by LKT Laboratories) dissolved in ethanol was added to 1ppm or 10 ppm. Wells (wells) to which no PT was added were used as control groups, respectively. Then, after 30 hours, the resulting mixture was replaced with MEM containing 2% by mass BSA (bovine serum albumin, manufactured by SIGMA) supplemented with 1ppm or 10ppm of Panaxatriol (PT) to perform desensitization (desensitization). After 18 hours, the 2% by mass BSA-containing MEM was removed, and 30. mu.L/well of KRH buffer (50mM HEPES (SIGMA corporation)) pH7.4, 137mM sodium chloride (manufactured by Wako pure chemical industries, Ltd.), 4.8mM potassium chloride (manufactured by Wako pure chemical industries, Ltd.), 1.85mM calcium chloride (manufactured by Wako pure chemical industries, Ltd.), and 1.3mM magnesium sulfate (manufactured by Wako pure chemical industries, Ltd.). Then, 6. mu.L of RI-labeled 2-deoxyglucose (2-DG, produced by American radio labeled Chemicals, USA) (final concentration 6.5mM (0.5. Ci)) was added and reacted. 5 minutes after the start of the reaction, the cells were washed 4 times with ice-cooled KRH buffer to remove 2-DG that had not entered the cells of L6. After removing the KRH buffer, the cells were dissolved in 250. mu.L of 0.05N sodium hydroxide (Wako pure chemical industries, Ltd.) and collected into a vial. Further, the reaction mixture was washed 2 times with 200. mu.L of KRH buffer and similarly recovered in a vial. To the vial from which the cells were collected, 3mL of Scintillation cocktail (Scintillation cocktail) Picoflour (Perkinelmer corporation) was added, and the radioactivity was measured by using a liquid Scintillation counter (LSC-5100, produced by Aloka).

The evaluation was performed when n is 4, and the average value was obtained. Statistical analysis was performed all according to Student's t-test, with P < 0.05 as a significant difference. The specific activity when the radioactivity was 100 without addition is shown in table 3 below.

[ Table 3]

*：P＜0.05，**：P＜0.01

< results >

According to table 3, an increase in the uptake of glucose into the cell interior was observed by adding PT to L6 cells.

These results suggest that the Panaxatriol (PT) -containing sugar metabolism-improving agent of the present invention has a sugar absorption-promoting effect in muscles, which are major organs in which a living body absorbs sugar.

(example 4: promotion of sugar entry into cells from rat skeletal muscle based on addition of PD)

< method >

According to the method described in example 3, rat skeletal muscle-derived cells (L6 cells, manufactured by Dainippon pharmaceutical Co., Ltd.) were suspended in 15mL of DMEM (Dulbecco's modified Eagle medium, manufactured by Dalbecco's modified Eagle medium, manufactured by SIGMA) containing 10 mass% of FBS (total bone serum, fetal bovine serum, manufactured by GIBCO Co., Ltd.) and 1 mass% of AB (anti-biological solution, manufactured by SIGMA Co., Ltd.), and 75cm of the cells were injected²After in the flask, 5% CO at 37 ℃₂The culture is performed under static conditions. After reaching sub-confluency (80%), 50000 cells/well were seeded on a 24-well plate (well plate) (Sumitomo Bakelite Co., Ltd.). After culturing for 3 days from the time of reaching confluency (confluency), MEM (minimum essential medium, produced by Nacalai Tesque corporation) containing 2 mass% FBS and 1 mass% AB was changed to induce differentiation of L6 cells. After inducing differentiation for 8 days, Panaxadiol (PD) dissolved in ethanol (LKT Laboratories, Inc.) was added to 1ppm or 10 ppm. Wells (wells) to which no PD was added were used as control groups, respectively. Then, after 30 hours, the resulting mixture was replaced with MEM containing 2% by mass BSA (bovine serum albumin, manufactured by SIGMA) supplemented with 1ppm or 10ppm of ginseng diol (PD) to perform desensitization (desensitization). After 18 hours, the 2% by mass BSA-containing MEM was removed, and 30. mu.L/well of KRH buffer (50mM HEPES (SIGMA Co., Ltd.), pH7.4, 137mM sodium chloride (Wako pure chemical industries, Ltd.), 4.8mM potassium chloride (Wako pure chemical industries, Ltd.), 1.85mM calcium chloride (Wako pure chemical industries, Ltd.), 1.3mM magnesium sulfate (Wako pure chemical industries, Ltd.) was added. Then, 6. mu.L of RI-labeled 2-deoxyglucose (2-DG, produced by American radio labeled Chemicals, USA) (final concentration 6.5mM (0.5. Ci)) was added and reacted. 5 minutes after the start of the reaction, the cells were washed 4 times with ice-cooled KRH buffer to remove 2-DG that had not entered the cells of L6. RemovingAfter KRH buffer, the cells were dissolved in 250. mu.L of 0.05N sodium hydroxide (Wako pure chemical industries, Ltd.) and collected into a vial. Further, the reaction mixture was washed 2 times with 200. mu.L of KRH buffer and similarly recovered in a vial. To the vial from which the cells were collected, 3mL of Scintillation cocktail (Scintillation cocktail) Picoflour (Perkin Elmer Corp.) was added, and the radioactivity was measured by using a liquid Scintillation counter (LSC-5100, produced by Aloka).

The evaluation was performed when n is 4, and the average value was obtained. Statistical analysis was performed all according to Student's t-test, with P < 0.05 as a significant difference. The specific activity when the radioactivity was 100 without addition is shown in table 4 below.

[ Table 4]

*：P＜0.05，**：P＜0.01

< results >

According to table 4, an increase in the uptake of glucose into the cell interior was seen by adding PD to L6 cells.

These results suggest that the Panoxadiol (PD) -containing sugar metabolism-improving agent of the present invention has a sugar absorption-promoting effect in muscles, which are major organs in the living body to absorb sugar.

Example 5 PT ingestion human test

< measurement of sugar metabolism-related index >

Method-

After suspending 10g of notoginseng powder in 100mL of 30 mass% ethanol aqueous solution, saponins were extracted by heating for 2 hours, and the obtained extract was hydrolyzed in the presence of hydrochloric acid to prepare a treated product containing aglycone. The aglycone-containing treated product was separated by using a silica gel column (silica gel 60N, kanto chemical corporation) to prepare Panaxatriol (PT) having a purity of 99% by mass or more.

Capsules containing 8mg of Panaxatriol (PT) prepared in this manner were prepared, and the postprandial blood glucose level change after eating a predetermined menu (menu loaded with starch food such as a rice ball (350kcal) using 200g of rice) was measured for fasting blood glucose level when continuously ingested for 8 weeks (hereinafter, sometimes referred to as "PT ingestion group"). Further, as blood indices, HbA1c value, glycated albumin value, 1 · 5AG, and fasting insulin value in blood were measured.

The blood glucose level was measured using a simple blood glucose meter (produced by Nipro corporation), the fasting blood glucose level and the fasting insulin level were measured at 9 am, the postprandial blood glucose level was measured at 30 minutes from 9 am to 11 am, and the measurement was performed every 30 minutes until 120 minutes after the ingestion of a predetermined starch food. The HbA1c value, the glycated albumin value, and 1 · 5AG were measured by a conventional method in the medical institution using blood collected at 9 am.

The subjects (24) had fasting blood glucose values of 120mg/dL to 140mg/dL, and were assigned placebo intake groups as controls, and 24 subjects were randomly divided into 2 groups, namely, a placebo intake group and a PT intake group. In addition, for statistical analysis of the results, Student t-test comparing placebo intake group and PT intake group was performed. The time period for taking the capsules was 10 am every day, and a time period not taken simultaneously with a meal was set.

FIG. 1 shows the results of measurement of fasting blood glucose level.

Fig. 2 shows the change in postprandial blood glucose values for the placebo intake group and fig. 3 shows the change in postprandial blood glucose values for the PT intake group.

The measurement results of the blood indices of the placebo-ingested group are shown in the following table 5, and the measurement results of the blood indices of the PT-ingested group are shown in the following table 6.

[ Table 5]

[ Table 6]

*：P＜0.05，**：P＜0.01，***：P＜0.001

Results-

The result of the PT intake human trial (example 5) was that fasting blood glucose values in the PT intake group were significantly reduced compared to the placebo intake group (fig. 1). The postprandial blood glucose levels in the PT intake group were significantly reduced 30, 60, and 120 minutes after intake, as compared with the placebo intake group, and significant glucose metabolism improvement effects were observed (fig. 2 to 3).

From these results, it was found that the diabetes-improving agent of the present invention containing Panaxatriol (PT) can lower both the fasting blood glucose level and the postprandial blood glucose level.

Furthermore, as a result of confirming the blood glucose metabolism-related index from tables 5 to 6, HbA1c in the PT intake group was significantly reduced after 8 weeks as compared with the placebo intake group. Glycated albumin was significantly reduced in the PT intake group compared to the placebo intake group. In addition, a significant decrease in glycated albumin was also seen between week 0 and week 8 in the PT uptake group. An increase in 1 · 5AG in the PT uptake group was seen after week 4. Since the fasting insulin values did not change statistically significantly in the PT intake group, it is presumed that the effect of inhibiting the increase in blood glucose level by Panaxatriol (PT) did not enhance insulin secretion but improved insulin sensitivity.

From these results, it was found that the diabetes-ameliorating agent of the present invention containing Panaxatriol (PT) does not need to be taken simultaneously with a meal, and since 1 intake of 1 time per day is effective, it is presumed that it is of great significance in promoting sustained intake.

Example 6 PD ingestion human test)

< measurement of sugar metabolism-related index >

Method-

After suspending 10g of notoginseng powder in 100mL of 30 mass% aqueous ethanol solution, saponins were extracted by heating for 2 hours, and the obtained extract was hydrolyzed in the presence of hydrochloric acid to prepare a treated substance containing aglycone. The aglycone-containing treated product was separated by using a silica gel column (silica gel 60N, manufactured by kanto chemical corporation) to prepare a Panaxadiol (PD) having a purity of 99% by mass or more.

Capsules containing 8mg of thus prepared Panaxadiol (PD) were prepared, and the postprandial blood glucose level change after eating a predetermined menu (menu loaded with starch food such as a rice ball (350kcal) using 200g of rice) was measured for fasting blood glucose value in 8 weeks (hereinafter, sometimes referred to as "PD ingestion group"). Further, as blood indices, HbA1c value, glycated albumin value, 1 · 5AG and fasting insulin value in blood were measured.

In addition, the subjects (24) had fasting blood glucose values of 120mg/dL to 140mg/dL, and the placebo intake group was reserved as a control, and 24 subjects were randomly divided into 2 groups, a placebo intake group and a PD intake group. In addition, statistical analysis of the results, Student's t-test comparing placebo and PD intake groups was performed. The time period for taking the capsules was 10 am every day, and a time period not taken simultaneously with a meal was set.

FIG. 4 shows the measurement results of fasting blood glucose level.

FIG. 5 shows the change in postprandial blood glucose values for the placebo intake group and FIG. 6 shows the change in postprandial blood glucose values for the PD intake group.

The measurement results of the blood indices of the placebo-ingested group are shown in the following table 7, and the measurement results of the blood indices of the PD-ingested group are shown in the following table 8.

[ Table 7]

[ Table 8]

*P＜0.05，**：P＜0.01，***：P＜0.001

Results-

As a result of the PD intake human trial (example 6), fasting blood glucose values were significantly reduced in the PD intake group compared to the placebo intake group (fig. 4). The postprandial blood glucose levels in the PD-ingested group were significantly reduced 30, 60, and 120 minutes after ingestion, as compared with the placebo-ingested group, and significant glucose metabolism-improving effects were observed (fig. 5 to 6).

From these results, it was found that the diabetes-improving agent of the present invention containing Panaxadiol (PD) can lower both the fasting blood glucose level and the postprandial blood glucose level.

Furthermore, according to tables 7 to 8, as a result of confirming the blood sugar metabolism-related index, HbA1c of the PD intake group was significantly reduced after 8 weeks as compared with the placebo intake group. Glycated albumin in the PD intake group was significantly reduced compared to the placebo intake group. In addition, a significant decrease in glycated albumin was also seen between week 0 and week 8 in the PD uptake group. An increase in 1 · 5AG was seen after week 4 in the PD uptake group. In the PD ingestion group, the fasting insulin value did not change statistically significantly, and it is presumed that the effect of inhibiting the increase in blood glucose level by Panaxadiol (PD) did not enhance insulin secretion but improved insulin sensitivity.

From these results, it was found that the diabetes-ameliorating agent of the present invention containing Panaxadiol (PD) does not need to be taken simultaneously with a meal, and since 1 intake of Panaxadiol (PD) is effective in 1 day, it is presumed to have a great significance in promoting sustained intake.

(example 7 sugar metabolism promoting Effect on sugar derived from food)

24 hyperglycemia model mice (KKAY mice (Japanese Clea Co., Ltd., male, 4 weeks old) were pre-fed in individual cages for 1 week at room temperature of 22. + -. 1 ℃ and humidity of 50. + -. 5% for 12 hours with alternating light and dark. The feed during the precursory period was administered to each mouse 8g of CE-2 (Nippon Clea Co., Ltd.) per day, and water was freely taken.

After the pre-feeding period, the body weight and blood glucose levels were measured and divided into 3 groups of 8 animals per group, and the animals were fed in the following manner. In addition, blood glucose levels were measured by collecting blood from the mouse tail vein and measuring whole blood using a rotary GB Sensor (manufactured by Sanko pure chemical industries, Ltd.).

Control group-

Each mouse was given 8g of a commercially available high-fat diet (trade name: QuickFat, manufactured by Nippon Clea Co., Ltd.) per day, and fed with water freely for 1 week. Hereinafter, the term "control group" is sometimes used.

PT administration group

Each mouse was given 8g of a commercially available high-Fat food (trade name: Quick Fat, manufactured by Nippon Clea Co., Ltd.) mixed with 0.1 mass% of Panaxatriol (PT) (manufactured by LKT Laboratories) per day, and was fed with water freely for 1 week. Hereinafter, the term "PT administration group" is sometimes used.

-PD administration group-

Each mouse was given 8g of a commercially available high-Fat diet (trade name: Quick Fat, manufactured by Nippon Clea Co., Ltd.) per day, and was fed with water freely for 1 week. Hereinafter, the term "control group" is sometimes used.

PT administration group

-PD administration group-

Each mouse was fed 8g of a commercially available high-Fat diet (trade name: Quick Fat, manufactured by Nippon Clea Co., Ltd.) mixed with 0.1 mass% of Panaxadiol (PD) (manufactured by LKT Laboratories) per day, and the diet was freely ingested with water and fed for 1 week. Hereinafter, sometimes referred to as "PD administration group".

After the feed is fed for 1 week, the blood sugar level and body weight are measured to provide¹³CO₂And (4) measuring the discharge amount. The blood glucose values of the control group were 335.4mg/dL, the PT administration group were 199.3mg/dL, and the PD administration group were 231.6 mg/dL.

<¹³CO₂Measurement of discharge amount>

The mice were transferred to an exhaled air analysis room (ARCO-2000-ISO System, manufactured by ARCO SYSTEM Co., Ltd.) and acclimatized for 2 hours. Then, glucose was synthesized from [2.0g D ] (Nacalai Tesque, Ltd.)Product) +72 mgD-glucose-U-13C₆(99%) (Cambridge Isotrope Lab. Co.)/kg-body weight]The calculated concentration is calculated by mixing glucose and glucose-U-13C₆The aqueous solution of (2) was orally administered to mice, and the accumulation over 4 hours was measured¹³CO₂And discharging the amount. Accumulation of¹³CO₂The output is expressed as AUC: (¹³CO₂Discharge amount increase value). So-called AUC: (¹³CO₂The increase in the output) of glucose-U-13C₆In the graph of the change of excretion versus time after administration, glucose-U-13C was used₆The output before administration was baseline until glucose-U-13C₆Area of the increased portion after 4 hours of administration.

FIG. 7A shows¹³CO₂The change with time of the discharge amount is shown in FIG. 7B¹³CO₂The result of discharging the amount. From these results, it can be seen that, in the PT administration group and the PD administration group,¹³CO₂the discharge amount significantly increases. (statistical analysis was performed according to the student test, with a significant difference of P < 0.05.) that is, the promotion of the metabolism of sugars ingested from food can be seen.

Industrial applicability

The glucose metabolism-improving agent comprising at least one of Panaxatriol (PT) and Panaxadiol (PD) and the glucose metabolism-improving composition containing the same according to the present invention are excellent in the action of promoting the entry of sugar into muscle cells, the action of suppressing the increase in postprandial blood glucose level, the action of lowering fasting blood glucose level, the action of regulating a marker related to sugar metabolism and the action of promoting the metabolism of sugar derived from food, and therefore can be suitably used as a postprandial blood glucose level increase inhibitor, a fasting blood glucose level lowering agent and a sugar absorption promoter, and are effective for the prevention and treatment of diabetes.

Further, the sugar metabolism-improving agent is highly safe and therefore can be suitably used for foods and beverages.

Claims

1. Use of at least either one of a compound represented by the following structural formula (1) and a compound represented by the following structural formula (2) for producing a sugar metabolism-improving agent and a composition thereof.

[ solution 5]

[ solution 6]

2. The use according to claim 1, wherein the sugar metabolism-improving agent has an effect of inhibiting an increase in postprandial blood glucose level.

3. The use according to claim 1, wherein the sugar metabolism-improving agent has at least one of an action of reducing fasting blood sugar level and an action of regulating an index relating to sugar metabolism in serum.

4. The use according to claim 1, wherein the sugar metabolism-improving agent has a metabolism-promoting effect of a sugar derived from a food.

5. The use according to claim 1, wherein the sugar metabolism-improving agent exerts a sugar metabolism-improving effect without being taken together with food.

6. The use according to claim 1, wherein the glucose metabolism-improving agent is ingested in an amount of at least 1mg per day.