JP6547121B2 - Blood sugar level rise suppressing composition - Google Patents

Description

The present invention relates to a composition for suppressing blood sugar level increase.

Obesity is known to cause a variety of diseases, and diabetes is one such disease. In the obese state, fat cell hypertrophy is observed, and not only fat cells but also target cells of insulin such as muscle cells and hepatocytes cause a decrease in insulin sensitivity at the cellular level. As a result, glucose tolerance deteriorates and diabetes eventually develops.

Insulin treatment is used to treat diabetes. However, regular insulin injections are required, and not only the burden on patients but also high self-management ability is required.

As an alternative to insulin injection, there is a medication for oral diabetes. As an oral diabetes therapeutic agent, for example, a sulfonylurea agent which promotes the secretion of insulin, an insulin resistance improving agent which acts on tissues and cells to lower the blood glucose level, an α-glucosidase inhibitor which inhibits the degradation of polysaccharides in the intestinal tract There is an agent. However, these drugs cause side effects such as excessive lowering of blood glucose levels to cause hypoglycemia.

The treatment of diabetes as described above is effective for persons with severe diabetes even if pain and side effects are caused by invasive methods. However, it is not effective at all for patients with mild diabetes or those who are concerned about elevated blood sugar levels even if diabetes is not achieved.

Therefore, components and compositions useful for the prevention and early treatment of diabetes have been reported so far, for example, Patent Documents 1 and 2 contain dry powder or extract of sweet potato stems and leaves and α-lipoic acid. An anti-obesity agent and a blood sugar level elevation inhibitor containing a pine bark extract and a dietary fiber are disclosed. In addition, Non-Patent Document 1 describes that indigestible dextrin has glucose tolerance.

JP, 2006-230225, A Japanese Patent Application Laid-Open No. 2002-275076

Shigeru Wakabayashi, The Japanese Journal of Endocrine Society, 68, 623-635 (1992)

Certainly, the anti-obesity agents described in Patent Documents 1 and 2 and the blood sugar level elevation inhibitor, and the indigestible dextrin described in Non-Patent Document 1 are effective against diabetes and obesity that causes diabetes. is there. However, these are substances whose active ingredients are derived from natural products, and are difficult to be industrially synthesized. In addition to these active ingredients, for example, if a substance having taste can suppress an increase in blood glucose level, it is very useful for diabetic patients and diabetes preventers.

Therefore, an object of the present invention is to provide a composition capable of inhibiting an increase in blood sugar level, which can be industrially synthesized and which contains a substance having taste as an active ingredient.

The inventors of the present invention have conducted intensive studies on various substances in order to solve the above problems, and surprisingly, starch decomposition products having a degree of polymerization of 2 or more such as maltobionic acid and lactobionic acid, transfer reactants or A composition containing a sugar carboxylic acid in which the aldehyde group on the reducing terminal side of lactose has been oxidized or a salt or lactone thereof exhibits an action to suppress an increase in blood glucose level and an action to reduce an early blood glucose level when administered together with glucose, In addition, it has been found that the degree is equal to or higher than the indigestible dextrin described in Non-Patent Document 1. As described in JP-A-2012-131750, sugar carboxylic acids can be chemically synthesized on an industrial scale using maltose, which is a starch decomposition product, starch syrup, dextrin, etc. as a raw material. . In addition, lactobionic acid can be microbiologically or enzymatically synthesized on an industrial scale using lactose as a raw material, as described in JP-A-2012-5401. Further, maltobionic acid and lactobionic acid which are sugar carboxylic acids can improve the taste as described in JP-A-47-20372. The present invention is a completed invention based on such findings.

Therefore, according to the present invention, one selected from the group consisting of a starch decomposition product having a polymerization degree of 2 or more, a transfer reactant, or a sugar carboxylic acid in which an aldehyde group on the reducing terminal side of lactose is oxidized, a salt thereof and a lactone thereof Alternatively, a composition for suppressing blood sugar level elevation comprising two or more species is provided.

Preferably, in the composition for suppressing blood sugar level elevation according to the present invention, the sugar carboxylic acid is selected from maltobionic acid, isomaltobionic acid, maltotrionic acid, isomaltotrionic acid, maltotetraonic acid, maltohexaonic acid and lactobionic acid. And one or more selected from the group consisting of

Preferably, the sugar carboxylic acid is contained in the form of malto-oligosaccharide oxide, branched oligosaccharide oxide, hydrous oxide, powdered oxide or dextrin oxide in the composition for suppressing blood sugar level elevation of the present invention.

Preferably, in the composition for suppressing blood sugar level increase according to the present invention, the salt is one or more selected from the group consisting of calcium salt, magnesium salt, sodium salt, iron salt, potassium salt, zinc salt and copper salt. including.

Preferably, in the composition for suppressing blood sugar level elevation according to the present invention, the lactone is maltobionolactone, isomaltobionolactone, maltotrionolactone, isomaltotrionolactone, maltotetraonolactone, maltohexaonolactone and It contains one or more selected from the group consisting of lactobinolactone.

By ingesting the composition for suppressing the elevation of blood glucose level of the present invention, the elevation of blood glucose level can be suppressed, and further, lowering of the blood glucose level can be expected. In addition, starch decomposition products having a polymerization degree of 2 or more such as maltobionic acid and lactobionic acid, which are active components of the composition for suppressing blood sugar level elevation of the present invention Since the acid is a substance having taste, the composition for suppressing blood glucose level rise of the present invention can be applied to oral use.

The oral composition of the present invention is most suitable for diabetes patients and those at risk of diabetes before or in parallel to taking antidiabetic drugs.

FIG. 1 is a diagram showing an outline of the test procedure described in the examples. FIG. 2: is the figure which showed the measurement result of the blood glucose level of Example 1 of an Example. Numbers and bars represent mean ± standard deviation. FIG. 3: is the figure which showed the measurement result of the blood glucose change value as described in Example 1 of an Example. Numbers and bars represent mean ± standard deviation. FIG. 4: is the figure which showed the measurement result of the blood glucose level of Example 2 of an Example. Numbers and bars represent mean ± standard deviation. FIG. 5: is the figure which showed the measurement result of the blood glucose change value of Example 2 of an Example. Numbers and bars represent mean ± standard deviation.

Hereinafter, the present invention will be described in detail.
The composition for suppressing the elevation of blood glucose level of the present invention is characterized by containing at least one or two or more selected from the group consisting of sugar carboxylic acid and its salt and its lactone as an active ingredient.

In the present invention, a sugar carboxylic acid refers to a starch decomposition product having a polymerization degree of 2 or more, a transfer reaction product, or one in which an aldehyde group on the reduction terminal side of lactose is oxidized, and further includes the form of these salts and lactones.

Specific examples include maltobionic acid, isomaltobionic acid, maltotrionic acid, isomaltotrionic acid, maltotetraonic acid, maltohexaonic acid, lactobionic acid, maltooligosaccharide oxide, branched oligosaccharide oxide, hydrous oxide, Powdered oxide, dextrin oxide and the like can be mentioned. The sugar carboxylic acids preferably used in the present invention are maltobionic acid and lactobionic acid and their salts.

The sugar carboxylic acid used in the present invention may be in any form, liquid, powder, not only free acid, but also in the form of salt or lactone, or a combination thereof. In the form of a salt, calcium salt, magnesium salt, sodium salt, iron salt, potassium salt, zinc salt, copper salt and the like can be mentioned.

Sugar carboxylic acid is a method of oxidizing a starch decomposition product, transfer reaction product or lactose by a chemical oxidation reaction, or a reaction of causing a starch decomposition product, transfer reaction product or lactose to have a microorganism capable of oxidizing oligosaccharide or an oxidizing enzyme It can be manufactured by

As a chemical oxidation reaction, for example, in the presence of an oxidation catalyst in which palladium, platinum, bismuth or the like is supported on activated carbon or the like, starch decomposition products, transfer reactants or lactose and oxygen are catalytically oxidized in an alkaline atmosphere The method of obtaining sugar carboxylic acid depending on the case is mentioned.

Moreover, as a method using a microorganism having the ability to oxidize oligosaccharides, for example, using Pantoea, Acinetobacter, Burkholderia, Acetobacter, Gluconobacter, etc., a starch decomposition product, transfer reaction product or lactose is used. There is a method of obtaining a sugar carboxylic acid by microbial conversion or fermentation. As a specific example of the method, the method described in JP 2012-5401 A can be mentioned.

As a method using an oxidase, for example, a method of obtaining maltobionic acid and the like from a degraded product of starch, a transfer reaction product or lactose using an oxidase derived from a microorganism having the ability to oxidize oligosaccharides, Bacillus stearothermophila There is a method of obtaining a sugar carboxylic acid by a transfer reaction from a substrate composed of soluble starch or malto-oligosaccharide and gluconic acid using a highly transferable cyclodextrin synthetase derived from Bacillus sp.

As an example of the production method by the chemical oxidation reaction, first, 3 g of a 5 wt% platinum carbon catalyst is added to 100 ml of a 20 wt% maltose solution maintained at 50 ° C. and stirred at 600 rpm while blowing oxygen at 100 mL / min. The reaction pH is then maintained at pH 9.0 by dropwise addition of 10 N sodium hydroxide solution. Then, after completion of the oxidation reaction, the catalyst can be removed by centrifugation and membrane filter filtration to obtain a sodium maltobionate solution. Maltobionic acid can be obtained by desalting the sodium maltobionate solution thus obtained by cation exchange resin or electrodialysis.

Moreover, it is possible to prepare maltobion acid salt by adding various salts to maltobionic acid, and when using maltobionic acid, it is also possible to prepare maltobiono delta lactone by dehydration operation. Maltobiono delta lactone rapidly becomes maltobionic acid when dissolved in water.

As a method for producing calcium maltobionate, for example, a method in which a calcium source such as calcium carbonate is added to the maltobionic acid solution obtained by the above method so as to have a molar ratio of 2: 1, and the like can be mentioned. The calcium source is not particularly limited. For example, it is edible calcium, and specifically, natural materials such as eggshell powder, coral powder, bone powder and shell powder, and chemically synthesized products such as calcium carbonate and calcium chloride is there.

The sugar carboxylic acid has an action to suppress an increase in blood glucose level caused by the influence of the sugars simultaneously ingested as described in the examples described later, and an action to early decrease the elevated blood glucose level. In addition, it may be considered that sugar carboxylic acid may alleviate or reduce not only the influence of simultaneously ingested sugar but also the influence of ingested sugar before or after the intake of sugar carboxylic acid.

The amount of sugar carboxylic acid used is not particularly limited as long as it exhibits an action of suppressing blood sugar rise when ingested, and can be appropriately set according to the type and form of the blood sugar rise suppression composition, etc. The amount of the composition is 0.0001 wt% to 100 wt%, preferably 0.001 wt% to 50 wt%, and more preferably 0.01 wt% to 30 wt% with respect to the composition for suppressing blood sugar level rise. When the composition for suppressing blood sugar level elevation contains a blood sugar level increasing component such as sugar, the amount of sugar carboxylic acid used is increased, and when it further contains another blood sugar level elevation suppressing component different from sugar carboxylic acid, The amount of use can be reduced.

The use form of the sugar carboxylic acid is not particularly limited. For example, a liquid sugar carboxylic acid itself or a liquid sugar carboxylic acid supported on a carrier can be used.

The composition for suppressing the elevation of blood glucose level of the present invention can exhibit an action of suppressing the elevation of blood glucose level and an action of lowering the early blood glucose level by containing the sugar carboxylic acid as an active ingredient. However, among these effects, the composition for suppressing the increase in blood glucose level of the present invention only needs to exhibit at least the action for suppressing the increase in blood glucose level. The composition for suppressing blood glucose level rise of the present invention can be used in various forms for the purpose of obtaining the effect. For example, it may be used for various purposes without adding special treatment. The composition for suppressing the elevation of blood glucose level of the present invention can take the form of an inhibitor of elevation of blood glucose level.

The daily intake of the composition for suppressing blood sugar level elevation of the present invention is not particularly limited, and may be appropriately set according to the degree of blood sugar level of the user and the manner of intake, but for example, 0.1 to 5,000 mg / kg, preferably 1 to 2,000 mg / kg, and more preferably 10 to 1,000 mg / kg, based on the weight of the user.

As described above, the form of utilization of the composition for suppressing blood sugar rise of the present invention is not particularly limited, but, for example, it can be a composition for suppressing blood sugar elevation for oral use. The form of the composition for suppressing the increase in blood glucose level of the present invention is not particularly limited, and can be any form. The form of the composition for suppressing an increase in blood glucose level of the present invention is, for example, a form suitable for oral intake, specifically, liquid, powder, granular, granular, tablet, rod, plate, block, Examples include solid, round, paste, and capsules such as hard capsules and soft capsules, caplets, tablets, and gels. As a specific example of the oral blood glucose level elevation suppressing composition of the present invention, a liquid oral oral blood glucose level elevation inhibiting composition may be mentioned.

The method of using the composition for suppressing blood sugar level elevation of the present invention is not particularly limited. For example, when it is in the form of a liquid, it is orally taken by drinking the liquid as it is or by diluting with water or the like. be able to. Such liquid material and other solid material may be mixed and taken orally, depending on the taste of the user and the like.

The composition for suppressing the elevation of blood glucose level of the present invention can have only sugar carboxylic acid as a single component, or can be a combination of sugar carboxylic acid and other components. The other components are not particularly limited, but, for example, thickeners, brighteners, manufacturing agents and the like can be used as the other components. Besides these, various excipients, binders, lubricants, stabilizers, diluents, extenders, thickeners, emulsifiers, colorants, perfumes and the like can be used as other components. The content of the other components can be appropriately selected according to the form of the composition for suppressing the elevation of blood glucose of the present invention and the like.

The composition for suppressing the elevation of blood glucose level of the present invention has an action of suppressing the elevation of blood glucose level and an early lowering action of blood glucose level. It is very useful for maintaining the health of diabetics and obese people.

The composition for suppressing the increase of blood glucose level for oral administration of the present invention has a function of suppressing the increase of blood glucose level. Moreover, since sugar carboxylic acid is a taste substance, it is possible to apply to oral use.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples, and the present invention can take various aspects as long as the problems of the present invention can be solved. .

[Example 1. Inhibitory effect of malto-oligosaccharide oxide on blood sugar level rise]
As described below, rats were used to evaluate the action of malto-oligosaccharide oxide containing maltobionic acid to suppress the increase in blood glucose level.

(1) Test substance Malto-oligosaccharide oxide mainly composed of maltobionic acid (viscous liquid; Sanei Saccharification Co., Ltd.) and indigestible dextrin (white powder; Matsutani Chemical Industry Co., Ltd.) as a reference example Was used. In addition, D-(+)-glucose (white powder; manufactured by Nacalai Tesque, Inc.) was used as a saccharide to be administered together with the test substance. In the malto-oligosaccharide oxide (HPLC method; converted to solid content), 3.5 wt% of gluconic acid, 20.3 wt% of maltotrionic acid and maltotetraonic acid (polymerization degree 4) in addition to 65 wt% of maltobionic acid Contains about 11 wt% of the above maltoligosaccharide oxide.

(2) Test sample Using distilled water as a solvent, glucose and each test substance were prepared to have the concentrations described in Table 1 below, and used as test samples.

(3) Test Animal A 6-week-old male SD rat (obtained from Kyudo Co., Ltd.) was acclimated for 6 days in a test environment. Thus, 7-week-old rats were used for the test, and grouping was performed so that blood glucose levels and body weights of healthy test animals become almost uniform on the day of the test. At the time of habituation, MF solid feed (manufactured by Oriental Yeast Co., Ltd.) and water were freely ingested. During the test, SD rats were fasted for 16 hours or more from the day before the test.

(4) Test procedure As shown in Table 2 below, the test animals were divided into 6 groups so that the blood glucose level and body weight before test sample administration (0 minutes) become uniform ( Priority: blood sugar level> body weight). The test sample corresponding to glucose 2,000 mg / kg and each group was orally administered by gavage (10 mL / kg). Blood was collected from the tail vein 30 and 120 minutes after administration, and the blood glucose level was measured using a small blood glucose level measuring instrument (Gultest Ace; manufactured by Sanwa Chemical Research Institute, Inc.). Using the blood glucose level as an index, the blood glucose level increase inhibitory action of malto-oligosaccharide oxide was evaluated. In addition, the dose of malto-oligosaccharide oxide is set to 3 doses in a 3-fold common ratio with 540 mg / kg as the maximum dose, and the malto-oligosaccharide oxide high dose group, malto-oligosaccharide oxide dose group and malto-oligosaccharide oxide are respectively Low dose group. A group to which only glucose without test substance was administered was used as a control group, and a group to which indigestible dextrin was administered instead of maltobionic acid was used as indigestible dextrin group. An overview of the test procedure is shown in FIG.

Oral gavage of the test sample was performed using a sonde at 10 mL / kg of the test sample based on the weight of the test day for each individual test animal. Moreover, the electronic balance for animals was used for the measurement of body weight.

(5) Statistical processing The numerical value obtained by measurement measured the mean value (mean) and the standard deviation (SD) in each group. The test was performed by two-group comparison (t-test without correspondence) between the control group and each test substance group. The significance level was 5% and 1%.

(6) Blood glucose level measurement result The transition result of the blood glucose level is shown in Table 3 and FIG. In the indigestible dextrin group, the blood glucose level tended to decrease 30 minutes after administration as compared to the control group (p = 0.06). A significant decrease was seen 30 minutes after administration in the malto-oligosaccharide oxide high dose group (p <0.05). A significant decrease was seen 30 minutes after administration in the malto-oligosaccharide oxide medium dose group (p <0.01, p <0.05, respectively). There was a significant decrease at 30 and 120 minutes after administration in the malto-oligosaccharide oxide low dose group (p <0.01, p <0.05). As described above, from the test group using malto-oligosaccharide oxide, malto-oligosaccharide oxide has an action to suppress a sharp rise in blood glucose level accompanying glucose administration, and further alleviates the influence of glucose administration earlier It turned out that it has the effect | action which reduces a blood glucose level.

(7) Blood glucose change value result The result of the blood glucose change value which shows the change of the blood glucose level on the basis of the blood glucose level before test sample administration (0 minute) is shown in Table 4 and FIG. As compared with the control group, the indigestible dextrin group showed a significant decrease 30 minutes after administration (p <0.05). In the malto-oligosaccharide oxide high dose group, a significant decrease was seen 30 minutes after administration (p <0.05). A significant decrease was seen 30 minutes after administration in the maltoligosaccharide oxide medium dose group (p <0.01, p = 0.07, respectively). The malto-oligosaccharide oxide low dose group showed a significant decrease at 30 minutes after administration and a tendency to decrease after 120 minutes (p <0.05, p = 0.05, respectively). As described above, from the test group using malto-oligosaccharide oxide, malto-oligosaccharide oxide has an action to suppress a sharp rise in blood glucose level accompanying glucose administration, and further alleviates the influence of glucose administration earlier It turned out that it has the effect | action which reduces a blood glucose level. In particular, a significant blood glucose level lowering effect was observed in the malto-oligosaccharide oxide high dose group.

As mentioned above, when malto-oligosaccharide oxide was administered, the blood glucose level raise inhibitory effect was confirmed not only in a dose. In particular, it is surprising to find that even at low doses (60 mg / kg), the action to suppress the rise in blood glucose level was observed. In particular, malto-oligosaccharide oxide is itself a carbohydrate, and therefore an event capable of suppressing an increase in blood glucose level by malto-oligosaccharide oxide is a very unique phenomenon which was first discovered by the present inventors.

[Example 2. Inhibitory effect of maltobionate and lactobionate on blood sugar elevation]
As described below, rats were used to evaluate the antihyperglycemic effect of maltobionate and lactobionate.

(1) Test Substance As an example, calcium maltobionate (manufactured by Sanei Saccharification Co., Ltd.), calcium lactobionate (manufactured by Sanei Saccharification Co., Ltd.) and maltoligosaccharide oxide (manufactured by Sanei Saccharification Co., Ltd.) were used. Moreover, D-(+)-glucose (made by Nacalai Tesque, Inc.) was used as saccharides administered with a to-be-tested substance. In addition, in maltobionic acid (HPLC method; converted to solid content), in addition to 67.2 wt% of maltobionic acid, 0.7 wt% of gluconic acid, 24.4 wt% of maltotrionic acid and maltotetraonic acid (polymerization degree 4) It contains about 7.7 wt% of the above maltoligosaccharide oxide. Calcium maltobionate and calcium lactobionate are equivalent to pure products.

(2) Test sample Using distilled water as a solvent, glucose and each test substance were prepared to have the concentrations described in Table 5 below, and used as test samples.

(3) Test Animal Eight-week-old male SD rat (obtained from Kikusei Co., Ltd.) was acclimated for 6 days under the test environment. Thus, 9-week-old rats were used for the test.

(4) Test procedure As shown in Table 6 below, the test animals were divided into 5 groups so that the blood glucose level and the body weight before test sample administration (0 minutes) become uniform ((4)) Priority: blood sugar level> body weight). The test sample corresponding to glucose 2,000 mg / kg and each group was orally administered by gavage (10 mL / kg). The subsequent test procedure was carried out as in Example 1.

(5) Statistical processing The numerical value obtained by measurement measured the mean value (mean) and the standard deviation (SD) in each group. The test was performed by two-group comparison (t-test without correspondence) between the control group and each test substance group. The significance level was 5% and 1%.

(6) Blood glucose level measurement result The transition result of the blood glucose level is shown in Table 7 and FIG. The test substance group showed a tendency to decrease in blood glucose level 30 minutes after administration as compared with the control group. In particular, significant decreases were observed 30 minutes after administration in the maltobionic acid Ca 1000 group, maltobionic acid Ca 500 group, and lactobionic acid Ca 2000 group (p <0.05), and in the malto-oligosaccharide oxide 60 group, significant reduction was observed 30 minutes after administration Was observed (p <0.01). As described above, calcium maltobionate and calcium lactobionate have the effect of suppressing the rapid rise in blood glucose level accompanying glucose administration as well as malto-oligosaccharide oxide, and further alleviate the influence of glucose administration earlier and thereby achieve blood glucose It turned out that it has the effect | action which reduces a value.

(7) Blood glucose change value result The result of the blood glucose change value which shows the change of the blood glucose level on the basis of the blood glucose level before test sample administration (0 minute) is shown in Table 8 and FIG. As compared with the control group, the test substance group showed an overall downward tendency at 30 minutes after administration. In particular, significant reductions were observed 30 minutes after administration in the maltobionic acid Ca 1000 group and maltobionic acid Ca 500 group (p <0.05), and a remarkable reduction was seen 30 minutes after administration in the maltoligosaccharide oxide 60 group (p p <0.01). In addition, it was shown that the lactobionic acid Ca2000 group also has a significant tendency as compared with the control group (p <0.10). As described above, calcium maltobionate and calcium lactobionate have the effect of suppressing the rapid rise in blood glucose level accompanying glucose administration as well as malto-oligosaccharide oxide, and further alleviate the influence of glucose administration earlier and thereby achieve blood glucose It turned out that it has the effect | action which reduces a value.

The composition for suppressing the elevation of blood glucose level according to the present invention can provide an oral composition which can be expected to have an action for suppressing the elevation of blood glucose level and an early stage of lowering the blood glucose level which can be taken orally. Useful for maintaining the health of the elderly. Therefore, since the present invention can prevent or treat a disease associated with diabetes, it contributes to the entire national economy, such as reduction of medical expenses associated with these diseases and elimination of labor reduction. .

Claims (2)

Maltobionic acid, isomalt Lactobiono acid containing malto-trione acid, isomalt trione acid, maltotetraose propionic acid, one or more selected from maltohexaose propionic acid and lactobionic acid and their salts or Ranaru group, blood glucose Value rise control composition. The composition according to claim 1, wherein the salt comprises one or more selected from the group consisting of calcium salt, magnesium salt, sodium salt, iron salt, potassium salt, zinc salt and copper salt. object.