JPH09208474A - Blood sugar value increase-suppressing agent and composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a blood sugar value increase-suppressing agent suitable for preventing and curing of abnormal blood sugar value such as diabetes mellitus, containing an oligogalacturonic acid. SOLUTION: This blood sugar value increase-suppressing agent contains an oligogalacturonic acid of the formula and/or its salt ((n) is 0-20). Preferably, at least one kind selected from a compound of the formula or its salt is contained in the agent to make a medical composition, and the composition is used as a medicine or eating and drinking. This agent has slight side effect and can mildly reduce a blood sugar value. An administrating amount of the agent is 10-100,000mg for an adult per 1 day, in dividing to 1-several times and optimally is administered per os. The compound of the formula is readily obtained by hydrolyzing or acid-hydrolyzing pectin by an enzyme such as pectinase.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a blood sugar level elevation inhibitor suitable for prevention or amelioration of abnormal blood sugar level such as diabetes and a composition containing the same.

[0002]

2. Description of the Related Art Changes in eating habits are remarkable in the modern era, and together with the tendency of aging, various new diseases have become a big problem. Such diseases include circulatory diseases such as hyperlipidemia, arteriosclerosis and arterial atheroma, and metabolic disorders such as diabetes caused by an increase in lipid intake and total energy intake. Can be mentioned. Above all, it must be said that diabetes is a very serious problem in view of difficulty in controlling prognosis and serious complications such as cataract.

As for the treatment of diabetes, insulin-dependent diabetes is treated by administration of insulin, but the administration of insulin requires a continuous small dose administration by an infusion pump, or an indwelling needle. It was necessary to administer the drug while monitoring the blood glucose level. Moreover, there was always a risk that incorrect administration timing could cause insulin-induced hypoglycemia, leading to serious life-threatening situations. That is, the treatment with insulin has a drawback that the administration timing is very difficult. In addition, there is no known mild drug that lowers blood glucose level, and the appearance of such drug has been awaited.

Treatment of non-insulin-dependent diabetes mellitus, which causes a rapid decrease in blood glucose level and which is not suitable for administration of insulin, requires only diet and exercise therapy, and the emergence of drugs for such diseases is awaited. Was there. Even in such diseases, a drug that mildly lowers blood sugar level is not known, and the appearance of such a drug has been awaited.

[0005]

The present invention has been made under such circumstances, and it is an object of the present invention to provide a compound that lowers blood sugar level mildly with few side effects.

[0006]

In view of such a situation,
The inventors of the present invention have conducted earnest studies to find a compound that lowers blood glucose levels with mild side effects, and as a result, the compound represented by the general formula (I), that is, oligogalacturonic acid and / or
Or, they found such action in physiologically acceptable salts thereof and completed the invention. Hereinafter, the present invention will be described in detail.

[0007]

Embedded image General formula (I) (However, in the formula, n represents an integer of 0 to 20.)

(1) Blood glucose level elevation inhibitor of the present invention The blood glucose level elevation inhibitor of the present invention comprises the compound represented by the general formula (I) and / or a physiologically acceptable salt thereof. Such a compound can be easily obtained by hydrolyzing pectin with an enzyme such as pectinase or by acid hydrolysis. In addition, n can be divided into a single product by purifying these hydrolyzates by ultrafiltration or gel filtration. In the present invention, n may be a single one or may be unpurified with a distribution, but it is preferable to use a single one or one having a narrow distribution width. Here, n is preferably 0 to 20, and 1 to 1
5 is more preferable, and 1-8 is still more preferable. The salt can be used without particular limitation as long as it is physiologically acceptable, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, ammonium salts, Examples thereof include organic amine salts, basic amino acid salts, and transition metal salts such as manganese and iron. Among these, the most preferable ones are transition metal salts having a high effect, and among them, iron salts are most preferable. This salt is more preferable than the free form because it is more effective than the free form. Here, the salt in the present invention means a chemical equivalent of 1:
It is meant to include not only the salt which is 1, but also the complex whose quantitative ratio is different from the chemical equivalent. The salt of the compound represented by the general formula (I) can be produced by mixing the compound represented by the general formula (I) and the corresponding base with water or the like as a medium.

As shown in the Examples below, the agent for suppressing increase in blood glucose level of the present invention is excellent in safety and mildly lowers blood glucose level. Therefore, the daily dose is 10 to 100,000 mg per adult per day. May be administered once or in several divided doses. The administration route is oral administration,
Examples thereof include injection into veins, arteries, portal veins, abdominal cavity, subcutaneous skin, administration by drip injection and the like. The most preferred of these is oral administration. This is because the oral administration of the blood glucose elevation inhibitor of the present invention exhibits excellent durability. Furthermore, oral administration is preferable in terms of ease of administration. Further, the blood glucose elevation inhibitor of the present invention is not only one that simply lowers the blood glucose level like insulin,
It has the effect of returning blood glucose levels beyond the normal level to the normal range. Therefore, there is no fear of causing hypoglycemia due to drug administration, and therefore the safety is high.

(2) Composition of the present invention The composition of the present invention is one or two selected from the compounds represented by formula (I) and physiologically acceptable salts thereof.
It is characterized by containing at least one species. The composition of the present invention is preferably used as a medicine or food and drink. This is because the blood sugar level increase inhibitor of the present invention has a mild blood sugar level suppression effect and high safety. For the formulation of the composition of the present invention, in addition to one or more selected from the compounds represented by the general formula (I) and physiologically acceptable salts, they are usually used in these medicines and foods and drinks. Can be included. Examples of such optional components include excipients, binders, coating agents, lubricants, sugar coating agents, disintegrating agents, bulking agents, flavoring agents, emulsifying / solubilizing / dispersing agents in pharmaceutical compositions. , Stabilizers, pH adjusters, isotonic agents, and the like. In food and drink, sweeteners, confectionery bases,
Examples thereof include flavoring agents, polysaccharides, emulsion stabilizers and thickeners. These compositions can be manufactured according to a conventional method. For example, it may be emulsified and mixed in a vacuum pot, or granulated by a granulator.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below with reference to examples, but it goes without saying that the present invention is not limited to these examples.

Example 1. Production Example 1. Pectin 1Kg, pectinase 50g and water 5
1 was stirred at 35 ° C. for 1 hour, ultrafiltered and lyophilized to obtain 123 g of a pectin hydrolyzate (blood glucose elevation inhibitor 1). This product is further produced by gel filtration and concentrated to give galacturonic acid (n = 0, blood sugar level elevation inhibitor 2).
30 g, dimer (n = 1, blood glucose elevation inhibitor 3) 11
g, trimer (n = 2, blood glucose elevation inhibitor 4) 8 g, tetramer (n = 3, blood glucose elevation inhibitor 5) 5 g, pentamer (n =
4, blood glucose level elevation inhibitor 6) 7 g, hexamer (n = 5, blood glucose level elevation inhibitor 7) 5 g, 7-mer (n = 6, blood glucose level elevation inhibitor 8) 4 g, octamer (n = 7, blood sugar elevation inhibitor 9)
3 g were obtained.

Example 2. Production Example 2 1 g of the blood glucose elevation inhibitors 2 to 9 and 1 g of ferrous chloride were dissolved in 200 ml of water, stirred at room temperature for 2 hours, purified by ultrafiltration, and freeze-dried for 48 hours, and then each complex. Galacturonic acid complex (blood glucose elevation inhibitor 10) 0.1 g, dimer complex (blood glucose elevation inhibitor 11) 0.4 g, trimer complex (blood glucose elevation inhibitor 12) 0.5 g, 4 Body complex (blood glucose elevation inhibitor 13) 0.8 g, pentamer complex (blood glucose elevation inhibitor 14) 1.3 g, hexamer complex (blood glucose elevation inhibitor 15) 1.2 g, 7-mer complex (Blood glucose level suppressor 16) 1.6 g, 8
1.1g of monomer complex (blood glucose elevation inhibitor 17)
Obtained.

Example 3. Example of compounding into candy The following component (A) is melted by heating at 150 ° C, cooled to 120 ° C, the component (B) is added, stirred and molded into a uniform product, and cooled to obtain a candy. It was

Example 4. Example of compounding into candy The following component (A) is melted by heating at 150 ° C, cooled to 120 ° C, the component (B) is added, stirred and molded into a uniform product, and cooled to obtain a candy. It was

Example 5. Example of compounding into gummy The following component (A) is melted by heating at 110 ° C., component (B) separately swollen and dissolved is added, and component (C) is further added, and the mixture is poured into a mold and left for one day and night. I took it off and got a gummy.

Example 6. Example of compounding into gummy The following component (A) is melted by heating at 110 ° C., component (B) separately swollen and dissolved is added, and component (C) is further added, and the mixture is poured into a mold and left for one day and night. I took it off and got a gummy.

Example 7. Capsule The following component (A) is uniformly mixed and stirred, and then (B)
The ingredients were added and thoroughly kneaded with a kneader. This was encapsulated with a capsule filling machine to prepare a capsule. (A) Squalene 15 Linolenic acid triglyceride 15 Wheat germ oil 10 Refined sardine oil 20 α-d tocopherol 0.2 (B) Defatted soybean powder 39.8 Blood sugar level elevation inhibitor 5 10

Example 8. Tablet The following ingredients are mixed uniformly and granulated by the fluidized bed granulation method,
Dried. This was tableted with a tableting machine to obtain tablets. Dextrin 15 Lactose 5 Palatinose 15 Potato starch 40 Magnesium stearate 5 Blood glucose elevation inhibitor 6 20

Example 9. Granules The following component (A) is placed in a glad granulator, and a 5% aqueous solution of component (B) is added dropwise to granulate, followed by drying at 40 ° C.
The particles were sized to obtain granules. (A) Lactose 67.5 Corn starch 10 Blood sugar level elevation inhibitor 7 20 (B) Hydroxypropyl cellulose 2.5

Example 10. Granules The following component (A) is placed in a glad granulator, and a 5% aqueous solution of component (B) is added dropwise to granulate, followed by drying at 40 ° C.
The particles were sized to obtain granules. (A) Lactose 67.5 Corn starch 10 Blood glucose level elevation inhibitor 8 20 (B) Hydroxypropyl cellulose 2.5

Example 11. Example of compounding into candy The following component (A) is melted by heating at 150 ° C, cooled to 120 ° C, the component (B) is added, stirred and molded into a uniform product, and cooled to obtain a candy. It was

Example 12. Example of compounding into candy The following component (A) is melted by heating at 150 ° C, cooled to 120 ° C, the component (B) is added, stirred and molded into a uniform product, and cooled to obtain a candy. It was

Example 13. Example of compounding into gummy The following component (A) is melted by heating at 110 ° C., component (B) separately swollen and dissolved is added, and component (C) is further added, and the mixture is poured into a mold and left for one day and night. I took it off and got a gummy.

Example 14. Example of compounding into gummy The following component (A) is melted by heating at 110 ° C., component (B) separately swollen and dissolved is added, and component (C) is further added, and the mixture is poured into a mold and left for one day and night. I took it off and got a gummy.

Example 15. Capsule The following component (A) is uniformly mixed and stirred, and then (B)
The ingredients were added and thoroughly kneaded with a kneader. This was encapsulated with a capsule filling machine to prepare a capsule. (A) Squalene 15 Triglyceride Linolenic Acid 15 Wheat Germ Oil 10 Refined Sardine Oil 20 α-d Tocopherol 0.2 (B) Defatted Soybean Powder 39.8 Blood Sugar Level Inhibitor 13 10

Example 16. Tablet The following ingredients are mixed uniformly and granulated by the fluidized bed granulation method,
Dried. This was tableted with a tableting machine to obtain tablets. Dextrin 15 Lactose 5 Palatinose 15 Potato starch 40 Magnesium stearate 5 Blood glucose elevation inhibitor 14 20

Example 17. Granules The following component (A) is placed in a glad granulator, and a 5% aqueous solution of component (B) is added dropwise to granulate, followed by drying at 40 ° C.
The particles were sized to obtain granules. (A) Lactose 67.5 Corn starch 10 Blood sugar level elevation inhibitor 15 20 (B) Hydroxypropyl cellulose 2.5

Example 18. Granules The following component (A) is placed in a glad granulator, and a 5% aqueous solution of component (B) is added dropwise to granulate, followed by drying at 40 ° C.
The particles were sized to obtain granules. (A) Lactose 67.5 Cornstarch 10 Blood glucose level elevation inhibitor 16 20 (B) Hydroxypropyl cellulose 2.5

Example 19. Granules The following component (A) is placed in a glad granulator, and a 5% aqueous solution of component (B) is added dropwise to granulate, followed by drying at 40 ° C.
The particles were sized to obtain granules. (A) Lactose 67.5 Cornstarch 10 Blood glucose elevation inhibitor 17 20 (B) Hydroxypropylcellulose 2.5

[0031]

【Example】

Embodiment 1 FIG. Acute toxicity and toxicity test An acute toxicity test by oral administration was carried out using 1 group of 10 ddy mice each having a body weight of 15 to 25 g. As the sample, the blood glucose elevation suppressors 1 to 17 of Examples 1 and 2 were used. Each sample was made into a 30% physiological saline solution or dispersion, and 12 g / Kg was orally administered, and after 72 hours, life or death was determined. No deaths were observed in any of the groups. From this, it is clear that the agent for suppressing blood sugar level elevation of the present invention is highly safe.

Embodiment 2 FIG. Blood glucose elevation inhibitory effect Using ICR mice (male, 5 weeks old, body weight 25 to 30 g), the effect of the blood glucose elevation inhibitor under the sugar loading condition with sucrose was examined. That is, 1 group of 10 mice that had been fasted for 24 hours in advance, 19 groups were prepared. Glucose and a blood glucose elevation inhibitor 1-17 were added at 1 g / Kg to groups 1-17, and glucose and pectin were added at 1 g for group 18. / Kg each (comparative example), 1
Only 9 g of glucose was administered to group 9 (control example). Blood was collected from the tail vein before administration and 15 minutes after administration, and the blood glucose level was measured by the glucose oxidase method (Glucose B Test Wako, manufactured by Wako Pure Chemical Industries, Ltd.). The value obtained by subtracting the value before administration from the value after administration was taken as the blood glucose elevation value. The results are shown in Table 1 as the average value of each group. From this table, it can be seen that the blood sugar level elevation inhibitor of the present invention is excellent in the blood sugar level elevation inhibitory action. Further, it can be seen that the transition metal salt is more excellent in the effect of suppressing the increase in blood glucose level.

[0033]

[Table 1]

[0034]

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a compound which lowers blood glucose level mildly with few side effects.

Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display location C08B 37/06 C08B 37/06 // A23L 1/06 A23L 1/06

Claims (5)

[Claims] 1. A blood glucose elevation inhibitor comprising a compound represented by the following general formula (I) and / or a physiologically acceptable salt thereof. Embedded image General formula (I) (however, n represents an integer of 0-20 in the formula) 2. The blood sugar level elevation inhibitor according to claim 1, wherein n is 1 to 8 in the general formula (I). 3. The blood sugar level elevation inhibitor according to claim 1 or 2, which is a transition metal salt. 4. A composition for preventing or ameliorating dysglycemia, comprising the blood glucose elevation inhibitor according to any one of claims 1 to 3. 5. The use according to claim 4, which is a drug or food.
A composition as described.