JPH05117156A - Preventive and therapeutic agent for disease following hyperglycemia - Google Patents

Abstract

PURPOSE:To provide a medicine preparation useful for preventing and treating diseases following hyperglycemia, excellently suppressing rise in blood sugar after intake of saccharides such as sucrose or starch, comprising a guar gum hydrolyzate as an active ingredient. CONSTITUTION:A medicine preparation comprising a guar gum hydrolyzate, for example, prepared by hydrolyzing guar gum by using an enzyme produced by an alkaliphilic bacteria belonging to the genus Bacillus, preferably a guar gum hydrolyzate which has 4,000-50,000 average molecular weight, a composition ratio of mannose: galactose of 1.5-2.0:1.0 and has 100-1,000 op viscosity at 20 deg.C in 40wt.% aqueous solution, as an active ingredient. A dose of the compound is 1-10g daily, properly administered once and dividedly. The compound has high safety, is readily administered, easily added to foods and processed.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a drug for the purpose of preventing and treating diseases associated with hyperglycemia, such as diabetes, prediabetes, obesity, hyperlipidemia and arteriosclerosis. ..

[0002]

2. Description of the Related Art Hyperglycemia is a condition in which glucose in blood is abnormally elevated, and is usually a symptom of abnormally elevated blood glucose level due to intake of sugar. .. This hyperglycemic condition causes not only diabetes and pre-diabetes but also causes and exacerbating factors such as obesity, hyperlipidemia, arteriosclerosis, etc. Therefore, preventing the hyperglycemic condition can prevent and prevent these diseases. It is useful as a treatment method.

As prophylactic and therapeutic agents for such hyperglycemic symptoms, antidiabetic agents such as insulin and tolbutamide are known, but they are not used as general medicines because they are injections and have side effects.

On the other hand, gel-forming dietary fibers such as guar gum, pectin and glucomannan are known to suppress postprandial blood glucose elevation. It is speculated that the main mechanism of action is the result of suppression of sugar absorption due to the extension of gastric residence time by these gel-forming dietary fibers [Chemistry and organisms, Vol. 18, 95- 105 pages (198
0)]. However, since these gel-forming dietary fibers including guar gum are extremely viscous even at low concentrations and are hardly soluble, they are difficult to take when they are taken as oral preparations, and they are added to ordinary foods. Also, there is a drawback that processing is difficult. Furthermore, when excessive intake of these high-viscosity gel-forming dietary fibers causes excessive gastric retention in the stomach, symptoms such as stomach sensation and abdominal pain are a concern.

Therefore, the development of a drug which is easy to take, easy to add to foods and to be processed, and which does not cause side effects such as prolongation of gastric retention time and which suppresses an excessive rise in blood glucose after meals has been developed. Was wanted. The purpose of the present invention is to
It is an object of the present invention to solve the above-mentioned problems of the prior art and provide a preventive and therapeutic agent for hyperglycemic symptoms which is not only effective and safe but also easy to take.

[0006]

In view of such circumstances, the inventors of the present invention have made various studies and found that a hydrolyzate of guar gum improves postprandial hyperglycemia and is effective as a preventive and / or therapeutic agent for the above-mentioned various symptoms. Therefore, they have found that they are highly safe, easy to take, and easy to add to foods and to process, and have completed the present invention.

That is, the present invention provides a preventive and / or therapeutic agent for diseases associated with hyperglycemia, which comprises a guar gum hydrolyzate as an active ingredient.

The guar gum hydrolyzate, which is an active ingredient of the preventive and / or therapeutic agent for diseases associated with hyperglycemia of the present invention (hereinafter referred to as "inventive agent"), is obtained by hydrolyzing guar gum with an enzyme. There is no particular limitation as long as it is a low molecular weight substance. That is, the polysaccharide, which is the main component of guar gum, is said to have a β-1,4-D-mannopyranoside structure, and the guar gum hydrolyzate is the β-
Obtained by treatment with an enzyme suitable for hydrolyzing the 1,4-D-mannopyranoside structure. Examples of such enzymes include those disclosed in JP-A-63-36775 and JP-A-6-36775.
Alkaloidophilus bacillus AM-001 described in JP-A-3-56289.
(Alkalophilic Bacillus., A
M-001) (Microtech Lab. No. 8856), Alcalophyllic Bacillus AM-024 (Alkaloph)
ilic Bacillus. , AM-024) (Microtechnology Research Institute, Microbiology No. 8857) and Alcalophyllic Bacillus AM-044 (Alkalophilic Bac).
illus. , AM-044) (Microtechnology Research Institute, Microbiology Research Institute, 8858)
No.)]. As a basic hydrolysis method, the method described in JP-A-63-49093 can be mentioned.

Particularly preferred guar gum hydrolysates include, for example, low molecular weight substances which are easily soluble in water and have a low viscosity when dissolved in water, which are obtained by the method described in JP-A-2-248401. More specifically, the average molecular weight is 4,000 to 50,000 and the mannose:
It is a guar gum hydrolyzate having a composition ratio of galactose of 1.5 to 2.0: 1.0 and having a viscosity of 100 to 1,000 cp at 20 ° C. when made into a 40% by weight aqueous solution.

[0010] The guar gum hydrolyzate has an action of markedly suppressing the increase in blood sugar after ingestion of sugars such as sucrose and starch, and the administration thereof prevents or treats the above-mentioned symptoms associated with hyperglycemia. be able to.

In the agent of the present invention, a guar gum hydrolyzate is used alone, and appropriate additives such as general excipients, stabilizers, preservatives, binders and disintegrants are mixed to prepare a solution, a capsule, Appropriate dosage forms such as granules, pills, powders, tablets and the like can be selected and formulated and administered orally or enterally. Further, addition of guar gum hydrolyzate to an appropriate food product does not prevent it from being a nutritional food for the purpose of treatment. The guar gum hydrolyzate, which is an active ingredient of the drug of the present invention, is a dietary fiber derived from a natural product and is substantially harmless with respect to toxicity. The dosage of the drug of the present invention to humans should be determined according to individual age, body weight, and symptom. In most cases, the effective dose is 1 to 10 g per day as a guar gum hydrolyzate. Therefore, it is suitable to administer once or in divided doses.

[0012]

The blood sugar level when the guar gum hydrolyzate used in the present invention is simultaneously administered to experimental animals at the same time is
The value was significantly lower than that of the control group. The inhibitory effect on blood sugar elevation of this substance was also observed when starch was loaded. On the other hand, it did not affect the blood glucose level when glucose, which is a monosaccharide, was loaded. From these results, it was speculated that the guar gum hydrolyzate used in the present invention suppresses the enzymatic degradation of sucrose and starch ingested as food in the digestive tract. For the purpose of elucidating this point, as a result of a decomposition experiment using sucrose, maltose and starch as a substrate using a rabbit small intestinal mucosa homogenate, the guar gum hydrolyzate used in the present invention inhibits the hydrolysis of sucrose and maltose. Was recognized. On the other hand, no effect was observed in starch degradation experiments using mouse salivary gland homogenate and mouse pancreatic homogenate.

[0013]

EXAMPLES The present invention will be described in more detail by way of examples, but the present invention is not limited to these examples. Further, the guar gum hydrolyzate used in the following examples was prepared by the method described in JP-A-2-248401, but the lot used had properties such as an average molecular weight of 5,000 and a white color. It was an almost tasteless powder, and the dietary fiber content (by the enzyme gravimetric method) was 80% or more. The aqueous solution was neutral, colorless and transparent, and the viscosity of a 20% by weight solution was 12 cp at 20 ° C., and almost no coloration was observed even when heated alone or together with an amino acid.

Example 1 (Inhibitory Action on Blood Glucose Increase after Carbohydrate Loading) Male ICR mice (body weight: 35.5 to 46.0 g) were used for each experiment with 5 mice in each group. After fasting overnight, 1 g / 1 kg of sucrose, starch or glucose was orally administered to each group of mice, and guar gum hydrolyzate was orally administered at the same time.
Untreated guar gum and sodium carboxymethyl cellulose were administered as control substances. Blood was collected from the fundus venous plexus before and 30 minutes, 60 minutes, and 120 minutes after the glucose loading, and the plasma glucose concentration was measured by the glucose oxidase method (Glucose B Test Wako).
The results are as shown in Table 1.

[0015]

[Table 1]

The increase in blood glucose due to sucrose loading was suppressed by guar gum hydrolyzate in a dose-dependent manner. The inhibitory effect on blood sugar elevation of this substance was also observed in the case of starch load. On the other hand, it did not affect the increase in blood glucose due to glucose load. Carboxymethylcellulose sodium (CMC-Na) did not affect the increase in blood glucose due to sucrose and glucose loading. On the other hand, untreated guar gum suppressed both blood glucose increase due to sucrose and glucose loading.

Example 2 (Inhibitory action on the carbohydrate-degrading activity of rabbit small intestinal mucosa homogenate) A white conventional male rabbit (body weight: 3.0 to 3.5 kg) was sacrificed by exsanguination and the small intestine was excised. After freezing and thawing, 5 mM EDT
Homogenize in A buffer (pH 7.0) to 60,000
Centrifuge at 0 × g for 60 minutes. The resulting precipitate was recovered and resuspended in 10 mM potassium phosphate buffer (pH 7.0) to give a crude enzyme solution. Sucrose (2 as a substrate
0 mM), maltose (20 mM) and starch (2 mg / m)
l) was used. The composition of the reaction solution was 350 μl of 100 mM maleic acid buffer solution (pH 6.8), 100 μl of substrate solution, 50 μl of crude enzyme solution and 500 μl of test solution, and the test substance was dissolved in the maleic acid buffer solution. The reaction was carried out at 37 ° C. for 15 minutes, and the amount of glucose produced was measured by the glucose oxidase method. As shown in Table 2, the concentration of guar gum hydrolyzate 1 to 5% inhibited the decomposition of sucrose and maltose in a concentration-dependent manner. In contrast, untreated guar gum and CMC-Na showed no inhibition. On the other hand, guar gum hydrolyzate had no inhibitory effect on glucose production from starch.

[0018]

[Table 2]

[0019]

INDUSTRIAL APPLICABILITY The guar gum hydrolyzate used in the present invention is substantially non-toxic, and unlike untreated guar gum and pectin, it is water-soluble and has low viscosity and does not cause gastric retention of food. It is an indigestible dietary fiber that is safe and easy to use. Since guar gum hydrolyzate suppresses hyperglycemia after ingestion of sugars, it is used as an active ingredient for diseases associated with postprandial hyperglycemia, such as diabetes and prediabetes,
It has become possible to provide preventive and therapeutic agents for hyperlipidemia and arteriosclerosis. It is also possible to add a guar gum hydrolyzate to foods to provide a medical nutritional food for the above diseases.

Claims (2)

[Claims] 1. A preventive and / or therapeutic agent for a disease associated with hyperglycemia, which comprises a guar gum hydrolyzate as an active ingredient. 2. The preventive and therapeutic agent according to claim 1, wherein the guar gum hydrolyzate has an average molecular weight of 4,000 to 50,000.