JP2005035954A - Carbohydrate absorption inhibitor and hyperglycemia-preventing food - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a carbohydrate absorption inhibitor having high carbohydrate absorption inhibiting activity and being safe to human bodies and free from adverse effect even when it is daily ingested as a food, a hyperglycemia-preventing food and a food for preventing and improving diabetes mellitus, obesity or hyperlipemia. <P>SOLUTION: The carbohydrate absorption inhibitor comprises an extract of Desmodium abscendens as an active ingredient. The hyperglycemia-preventing food comprises an extract of Desmodium abscendens. The food for preventing and improving diabetes mellitus, obesity or hyperlipemia comprises an extract of Desmodium abscendens. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a carbohydrate absorption inhibitor and a hyperglycemia-preventing food, and more particularly to a carbohydrate absorption inhibitor, a hyperglycemia-preventing food, and a food for preventing or improving diabetes, obesity or hyperlipidemia.

  In Japan, eating habits have become richer, and is now called the age of satiety, and due to excessive caloric intake and lack of exercise, obesity or diabetes is rapidly increasing. Currently, one in three males in their 30s is overweight or obese, and nearly 40% are overweight in the 40-50s. In addition, the number of diabetic patients is 13.7 million including the reserve army, and the number is increasing.

On the other hand, carbohydrates and saccharides taken from meals are first roughly decomposed by the action of α-amylase contained in saliva and α-amylase secreted from the pancreas, and then the glucoside bond present at the non-reducing end. By the action of α-glucosidase, which is a disaccharide-degrading enzyme such as maltase or sucrase, which is cleaved, monosaccharide glucose is finally decomposed and absorbed from cilia on the mesentery.
Thereafter, the absorbed glucose temporarily increases the blood glucose level, resulting in hyperglycemia. Usually, it returns to the original blood glucose level by rapid insulin secretion and a response to normal insulin.

  However, in a state where sensitivity to insulin is reduced due to overeating, diabetes, or abnormal lipid metabolism, it takes time to return to the original state and promotes a large amount of insulin secretion. This is a so-called abnormal glucose tolerance state. Such symptoms further promote obesity and diabetes.

Furthermore, if hyperglycemia persists, it leads to arteriosclerosis, kidney damage, retinopathy, and other serious diabetic complications due to glycation reaction with intravascular proteins.
In order to prevent and ameliorate such complications, it is important to strictly control blood glucose and to suppress postprandial hyperglycemia, and to suppress excessive insulin secretion and eliminate the burden on the pancreas. It is thought that there is. In fact, disaccharide-degrading enzyme inhibitors have recently been developed as drugs, and their usefulness against diabetes has been recognized.
In other words, the onset of diabetes and obesity are thought to be caused by such a decrease in insulin sensitivity, and it is very important to suppress such postprandial hyperglycemia and excessive insulin secretion from the onset or early stage of diabetes.

In order to prevent the development and progression of diabetes due to impaired glucose tolerance and to suppress diabetic complications due to hyperglycemia, it is important to suppress hyperglycemia after meals. For that purpose, it is necessary to ingest the ingredient which suppresses the digestive absorption of the carbohydrate in a digestive tract with a meal.
However, at present, there are few things that can be ingested daily as food, and that prevent or improve them safely.
That is, the fact is that there is almost no thing that has a high carbohydrate absorption inhibitory activity and is safe and has no side effects even if it is ingested daily as a food, and has not yet reached a practical stage.

  The present invention solves the above-mentioned conventional problems, has a high carbohydrate absorption inhibitory activity, and is safe for the human body even when ingested daily as a food, and has no side effects, a carbohydrate absorption inhibitor, a food for preventing hyperglycemia, and The object is to provide foods for preventing and improving diabetes, obesity or hyperlipidemia, respectively.

  Therefore, as a result of searching for plants widely used for edible plants and having a carbohydrate absorption inhibitory effect, the present inventors have found that the manayupa extract has a strong α-amylase inhibitory action and a glucose absorption inhibitory action. In addition to finding out, it has been found that there is a hypoglycemic action based on such a carbohydrate absorption inhibitory action, and the present invention has been completed based on these findings.

That is, this invention which concerns on Claim 1 provides the carbohydrate absorption inhibitor which uses Manayupa extract as an active ingredient.
The present invention according to claim 2 provides a hyperglycemia-preventing food containing manayupa extract.
This invention which concerns on Claim 3 provides the foodstuff which prevents and improves diabetes, obesity, or hyperlipidemia containing Manayupa extract.

The carbohydrate absorption inhibitor of the present invention according to claim 1 has an α-amylase inhibitory action and significantly suppresses an increase in blood glucose after loading in a starch load test, but also against maltose, sucrose and glucose. Each inhibits absorption. Moreover, the hypoglycemic effect is recognized by continuous administration to the spontaneously diabetic Yellow KK mouse. Therefore, it has the action of inhibiting the degradation of starch itself and the action of inhibiting the absorption of glucose in the final absorption process, and these actions are considered to exhibit an antidiabetic action. Furthermore, cholesterol lowering action is also shown.
Therefore, the carbohydrate absorption inhibitor of the present invention according to claim 1, which comprises manayupa extract as an active ingredient, is used for prevention and improvement against diabetes, lifestyle diseases such as obesity and hyperlipidemia ( It is considered that the treatment is effective.
Since the carbohydrate absorption inhibitor of the present invention according to claim 1 is a edible material, it is safe and very excellent for daily ingestion and use. Moreover, since it has a strong activity by the hot water treatment, it can be used by adding to various foods, processed foods, pharmaceuticals and the like.

  In addition, the hyperglycemia-preventing food of the present invention according to claim 2 has a blood glucose lowering action based on the carbohydrate absorption inhibitory action shown in Manayupa extract, and is effective in preventing hyperglycemia.

  Further, the food for preventing or improving diabetes, obesity or hyperlipidemia of the present invention according to claim 3 has a hypoglycemic action or a cholesterol lowering action based on the carbohydrate absorption inhibitory action shown in Manayupa extract. It is effective in preventing and improving diabetes, obesity or hyperlipidemia.

The present invention according to claim 1 is a carbohydrate absorption inhibitor containing mana yupa extract as an active ingredient.
Manayupa's scientific name is Desmodium abscendens, which is called “Noharahagi” in Japanese. It belongs to the genus Leguminosae, and is a plant distributed in the tropics, temperate zones and the world.

The carbohydrate absorption inhibitor of the present invention according to claim 1 comprises such an extract of Manayupa as an active ingredient.
The extraction can be performed using water (including cold water, hot water, hot water), or an organic solvent such as methanol or ethanol. In particular, hot water extraction or extraction with methanol or ethanol is preferred.
Manayupa has stems, leaves and roots, but stems and leaves are preferred, and dry powders thereof can also be used.

The carbohydrate absorption inhibitor of the present invention according to claim 1 can be in various forms such as tablets, powders, granules, capsules, and liquids. Furthermore, those obtained by adding an appropriate excipient (for example, dextran, oligosaccharide, lactose, etc.) to these forms may be used. In addition, a nutritional supplement can be added to the preparation.
The amount of the carbohydrate absorption inhibitor of the present invention according to claim 1 is not particularly limited, but is usually about 0.01 to 5 g, preferably about 0.05 to 1 g, as the amount of mana yupa extract used per day. It is recommended to use it once or several times a day so that it is ingested.

The present invention according to claim 2 is a hyperglycemia-preventing food containing the mana yupa extract as described above.
The antihyperglycemic food of the present invention according to claim 2 may be any food containing manayupa extract, may be manayupa extract itself, or more generally used in addition to manayupa extract. It may contain a food material.
Such an antihyperglycemic food of the present invention according to claim 2 can be used as a so-called functional food, and in the same manner as the carbohydrate absorption inhibitor of the present invention according to claim 1, tablets, powders, granules , Capsules, liquids, etc., and suitable excipients (eg, dextran, oligosaccharides, lactose, etc.) can be added to these forms. It can also be added and used.
The hyperglycemia-preventing food of the present invention according to claim 2 exhibits a hypoglycemic action based on a carbohydrate absorption inhibitory action.

The present invention according to claim 3 is a food for preventing or improving diabetes, obesity or hyperlipidemia, which contains the mana yupa extract as described above.
The food of the present invention according to claim 3 may be any food containing a mana yupa extract, like the hyperglycemia-preventing food of the present invention according to claim 2, or may be the mana yupa extract itself. Alternatively, in addition to the mana yupa extract, a food material that is generally used may be contained. Furthermore, like the hyperglycemia-preventing food of the present invention according to claim 2, it can be in various forms, and it can also be used by adding excipients and nutritional supplements.
In the food for preventing or improving diabetes, obesity or hyperlipidemia of the present invention according to claim 3, a hypoglycemic action or a cholesterol lowering action based on the carbohydrate absorption inhibitory action shown in Manayupa extract is recognized, It is effective in preventing and improving diabetes, obesity or hyperlipidemia.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited only to a following example.

Production Example 1 (Methanol extraction)
8,000 ml of methanol was added to 1 kg of Manayupa dry leaves, refluxed for 3 hours, the methanol extract was concentrated to dryness, and the extract was partitioned between water and butanol. The butanol fraction was further divided into ether soluble and insoluble. 69 g of ether insoluble matter (ether insoluble fraction), 51 g of ether soluble matter (ether soluble fraction) and 21 g of water soluble fraction were obtained, respectively.

Production Example 2 (Hot water extract)
10,000 kg of water was added to 1 kg of Manayupa stalks and leaves and extracted in a boiling bath for 30 minutes. After concentration under reduced pressure with a rotary evaporator and lyophilization, 112 g of hot water extract was obtained.

Production Example 3 (Ethanol extract)
To 1 kg of Manayupa stems and leaves, 10,000 ml of ethanol was added and stored at room temperature for 3 days with occasional stirring to obtain an ethanol extract. This operation was repeated three times, and the filtrate was collected and concentrated under reduced pressure to obtain 26 g of ethanol extract powder.

Example 1 (α-amylase inhibition test and α-glucosidase inhibition test)
(1) α-Amylase Inhibition Test An α-amylase inhibition test was performed using the Manayupa extract obtained in Production Example 1. The test method is as follows.
As α-amylase, porcine pancreatic juice-derived α-amylase (SIGMA) was diluted with potassium phosphate buffer (pH 7.0). The α-amylase activity was measured using a commercially available amylase test Wako (manufactured by Wako Pure Chemical Industries, Ltd.). Add 25 μl of α-amylase to 25 μl of test solution dissolved in potassium phosphate buffer (pH 7.0), preincubate for 5 minutes at 37 ° C., and then add 200 μl of soluble starch solution dissolved at 50 mg / dl. And allowed to react at 37 ° C. for 10 minutes. The reaction was stopped by adding 250 μl of 0.01N iodine solution, and the color obtained by the iodine starch reaction by adding 1 ml of water was measured with a 660 nm absorptiometer. The inhibition rate of the test substance was calculated as follows.

First, the control amylase activity was calculated from the following formula I.
[Formula I]
Control amylase activity; (AB) / A × 100... I
Here, A and B are as follows.
A: Absorbance when a buffer solution is added instead of the test substance and enzyme B: Absorbance when a buffer solution is added instead of the test object and allowed to undergo an enzyme reaction

Next, the amylase activity of the test substance (Manayupa extract) was calculated from the following formula II.
[Formula II]
・ Amylase activity of test article; (CD) / A × 100... II
Here, C and D are as follows.
C: Absorbance when buffer is added instead of enzyme D: Absorbance when enzyme and test substance are added

And the amylase inhibitory activity rate of the test object was computed from the above Formula I and Formula II by the following Formula III.
[Formula III]
Test substance amylase inhibitory activity rate (%); (I-II) / I × 100

As a result, the amylase inhibitory activity rate of the test substance was 76% and 38% in the ether-soluble fraction and 106% and 83% in the ether-insoluble fraction, respectively, at the test substance concentration of 1 mg / ml and 0.1 mg / ml. It was 90% and 75% in the water-soluble fraction. Therefore, a strong α-amylase inhibitory action was shown in the ether insoluble fraction.
Therefore, the concentration dependency of the ether-insoluble fraction that showed a strong α-amylase inhibitory effect was examined. As a result, as shown in FIG. 1, a strong α-amylase inhibitory effect of 80% was shown even at a low test substance concentration of 0.05 mg / ml.

(2) α-Glucosidase Inhibition Test An α-glucosidase inhibition test was performed as follows using the same test substance.
Enzyme was obtained by homogenizing rat small intestine acetone powder with 0.1M phosphate buffer, dissolving the precipitate obtained by centrifugation in 1% Triton-X100, centrifuging, dialyzing the supernatant, and Using. Maltose or sucrose (14 mM) was used as a substrate, a crude enzyme solution was added, and after reaction for 15 minutes, the released glucose was quantified by the glucose oxidase method.
The inhibition rate was shown as the inhibition rate (%) by subtracting the activity at the time of adding the test substance from 100 when the test substance was not added.

  As a result, at the test substance concentrations of 1 mg / ml and 0.1 mg / ml, the inhibition rates were 32% and 2% for the ether-soluble fraction and 67% and 19% for the ether-insoluble fraction, respectively. The sex fraction was 36% and 9%.

Example 2 (Sugar absorption inhibition test; soluble starch loading test)
Using the ether-insoluble fraction (the ether-insoluble fraction of the Manayupa extract obtained in Production Example 1) that showed a strong α-amylase inhibitory action in Example 1, the carbohydrates to rats were as follows. An absorption inhibition test (starch load test) was performed.
A 6-week-old SD male rat was used, and a carbohydrate solution was administered immediately after oral administration of a test substance 500 mg / kg dissolved in physiological saline using a sonde. Blood was collected from the tail vein 30 minutes, 60 minutes and 120 minutes after the administration time of 0 minutes, and the glucose concentration was determined by the glucose oxidase method.
Soluble starch was orally administered to rats at 2 g / kg, and changes in blood glucose level were measured over time. In the test substance administration group, the ether-insoluble fraction 500 mg / kg of the Mana Yupa extract obtained in Production Example 1 was orally administered immediately before.
As a result, 30 minutes after administration of soluble starch, the manayupa extract (ether insoluble fraction) administration group showed an increase in blood sugar relative to the control group (control) that was not administered with manayupa extract (ether insoluble fraction). Significantly suppressed. Further, due to the delay of the ascending curve, the manayupa extract (ether insoluble fraction) administration group showed a significantly high value after 60 minutes as shown in FIG.

Example 3 (maltose load test)
In the starch tolerance test of Example 2, Manayupa extract was shown to significantly suppress the increase in blood sugar.
Therefore, in order to examine whether other saccharides are effective, an oral glucose tolerance test of maltose 2 g / kg was performed.
As a result, by administration of the ether-insoluble fraction of 500 mg / kg of the Manayupa extract obtained in Production Example 1, the Manayupa extract, as shown in FIG. The increase in blood glucose 30 minutes after administration was significantly suppressed compared to the control group (control), which was a group not administered with mana yupa extract (ether insoluble fraction).

Example 4 (sucrose load test)
A sucrose load test (2 g / kg) was performed using the ether insoluble fraction of the Manayupa extract obtained in Production Example 1.
As a result, as shown in FIG. 4, in the control group (control), which was not administered with the manayupa extract (ether insoluble fraction), a peak of blood sugar increase was obtained 30 minutes after administration, but the manayupa extract (ether insoluble fraction) was obtained. The fraction) administration group was significantly suppressed 30 minutes later than the control group (control), and showed a peak in blood sugar increase 60 minutes later.
That is, it was shown that administration of manayupa extract (ether-insoluble fraction) delayed the rapid increase in blood sugar, resulting in a gradual increase.

Example 5 (glucose tolerance test)
A glucose tolerance test (2 g / kg) was performed using the ether-insoluble fraction of the Manayupa extract obtained in Production Example 1.
As a result, as shown in FIG. 5, in the case of administration of manayupa extract (ether insoluble fraction) 500 mg / kg, after 30 minutes and 60 minutes, a remarkable blood glucose increase inhibitory effect was exhibited compared to the control group (control). .
In addition, even when Manayupa extract (ether insoluble fraction) was administered at a concentration of 300 mg / kg, a significant decrease was shown after 30 and 60 minutes compared to the control group (control).

Example 6 (glucose tolerance test; mana yupa hot water extract and mana yupa alcohol extract)
A glucose tolerance test was conducted using the manayupa hot water extract obtained in Production Example 2 and the manayupa alcohol extract obtained in Production Example 3 (each 500 mg / kg). The results are shown in FIG.
As a result, the glucose level significantly lower than that of the control group (control) was shown in both the Manayupa hot water extract administration group and the alcohol extract administration group after 60 minutes of glucose load.

As a result, the manayupa extract showed an inhibitory action on carbohydrate (starch) absorption by an inhibitory action on α-amylase. Manayupa extract also inhibited the absorption of maltose, sucrose and glucose.
On the other hand, as a result of examining the maltase inhibitory action and sucrase inhibitory action using the crude enzyme derived from the small intestine, Manayupa extract showed no inhibitory action.
Therefore, it was presumed that the manayupa extract has an absorption inhibitory action on glucose itself as well as an α-amylase inhibitory action.

Example 7
Using the ether-insoluble fraction of Mana Yupa extract obtained in Production Example 1, a spontaneous ingestion (continuous administration) test was performed on spontaneously diabetic Yellow KK mice, during which body weight change, blood glucose level change, blood Changes in lipid (total cholesterol level, triglyceride, free fatty acid) and blood insulin level were examined.
In this test, the ether-insoluble fraction of the Mana Yupa extract obtained in Production Example 1 was added to the feed at a concentration of 1% and allowed to freely ingest for 6 weeks.

The change in body weight during this test is shown in FIG.
As a result, weight gain was significantly suppressed by continuous administration of Mana Yupa extract (ether insoluble fraction) compared to the control group (control).
Moreover, the change of the blood glucose level during this test is shown in FIG.
As a result, the blood glucose level significantly decreased with respect to the control group (control) 2 weeks after the start of administration, and the blood glucose lowering action continued thereafter.
Next, regarding changes in blood lipids during this test, changes in total cholesterol values are shown in FIG. 9 , changes in triglyceride values are shown in FIG. 10, and changes in free fatty acids are shown in FIG.
As a result, 5 weeks and 6 weeks after the start of the test, a significant blood cholesterol lowering effect by continuous administration of Manayupa extract was shown. There were no significant changes in triglyceride values and free fatty acids.
Furthermore, FIG. 12 shows changes in blood insulin levels during this test.
As a result, the blood insulin level showed a significant decrease after 6 weeks.

In addition, about the amount of drinking water in this test, it decreased clearly in the mana yupa addition group.
At the end of the test, an insulin tolerance test was performed.
After fasting overnight, an insulin solution prepared to 0.5 U / kg was subcutaneously injected to the dorsal side to a weight of 0.5 ml / 50 g. Blood samples were collected from the tail vein before administration and 30 minutes, 60 minutes, and 120 minutes after administration, and changes in blood glucose levels were measured. As a result, as shown in FIG. 13, in the continuous administration group of manayupa extract, the rate of decrease in blood glucose level was significantly greater after 30 minutes of insulin loading than in the control group (control), and this tendency was continued until 120 minutes. Followed.

Example 8 (Continuous administration test to normal mice)
A continuous administration test to normal mice was performed using 4-week-old ddy male mice. The mice are divided into a control group (control) and a manayupa extract administration group. In the manayupa extract administration group, the ether insoluble fraction of the manayupa extract obtained in Production Example 1 is 1% in the diet (CE2). Mixed by concentration. Body weight was measured daily and blood glucose levels were measured weekly. After 6 weeks of continuous administration, blood insulin levels and blood lipids were measured.
As a result, no effect of continuous administration of manayupa extract on body weight and blood glucose level was observed. Moreover, there was no influence of continuous administration of manayupa extract on blood insulin level, blood triglyceride, blood cholesterol and free fatty acid.
Therefore, the carbohydrate absorption inhibitor of the present invention has no effect on blood sugar levels and blood lipids even when ingested for a long period of time in normal mice, and is effective only in a diabetes model. The safety was also shown.

The present invention uses an ingredient extracted from mana yupa as an active ingredient, suppresses the postprandial hyperglycemia by inhibiting carbohydrate absorption in the gastrointestinal tract, delays the progression of diabetes, and is thus a diabetic complication. Suppresses the development of hyperlipidemia, hypertension and arteriosclerosis, and prevents obesity.
Therefore, the present invention can be widely used in the food industry field.

2 is a graph showing the results of an α-amylase inhibitory activity test using various concentrations of manayupa extract in Example 1. FIG. 4 is a graph showing the results of a soluble starch load test in Example 2. 6 is a graph showing the results of a maltose load test in Example 3. It is a graph which shows the result of the sucrose load test in Example 4. 6 is a graph showing the results of a glucose tolerance test in Example 5. It is a graph which shows the result of the glucose tolerance test by the Manayupa hot-water extract and Manayupa alcohol extract in Example 6. It is a graph which shows the influence of the manayupa extract continuous administration on the body weight of the spontaneous diabetes yellow KK mouse | mouth in Example 7. FIG. It is a graph which shows the influence of the manayupa extract continuous administration on the blood glucose level of spontaneous diabetes yellow KK mouse in Example 7. It is a graph which shows the influence of the manayupa extract continuous administration on the total cholesterol level of spontaneous diabetes yellow KK mouse in Example 7. It is a graph which shows the influence of the continuous administration of manayupa extract on the triglyceride value of the spontaneous diabetes yellow KK mouse | mouth in Example 7. It is a graph which shows the influence of the manayupa extract continuous administration on the free fatty acid of the spontaneous diabetes yellow KK mouse | mouth in Example 7. FIG. It is a graph which shows the influence of the continuous administration of manayupa extract on the blood insulin level of the spontaneous diabetes mellitus Yellow KK mouse in Example 7. It is a graph which shows the influence of the continuous administration of manayupa extract on the blood glucose level after the insulin load with respect to spontaneous diabetes yellow KK mouse in Example 7.

Claims (3)

  A carbohydrate absorption inhibitor containing mana yupa extract as an active ingredient.   A hyperglycemia-preventing food containing Manayupa extract. A food containing mana yupa extract for preventing or improving diabetes, obesity or hyperlipidemia.

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