JP7064731B2 - Blood glucose lowering agent, 1,5-anhydroglucitol lowering agent and food and drink composition - Google Patents

Description

The present invention relates to hypoglycemic agents, 1,5-anhydroglucitol lowering agents and food and drink compositions.

The number of diabetic patients continues to increase rapidly due to the westernization of food and changes in lifestyle and social environment. Diabetes does not cure once it develops, and if left untreated, it causes various complications such as retinopathy, nephropathy, and neuropathy, and further puts pressure on medical expenses.

Conventionally, an insulin secretagogue has been used as an oral therapeutic agent for diabetes in order to reduce the amount of glucose in the blood. However, the insulin secretagogue has a large burden on the pancreas.

On the other hand, in recent years, SGLT (sodium-glucose transporter) inhibitors that utilize a mechanism different from the mechanism of insulin secretion have been developed. This SGLT inhibitor reduces the amount of sugar in the urine that is reabsorbed into the body through the tubules and increases the amount of sugar contained in the urine that is excreted from the body, thereby removing excess blood from the blood. Since it uses a mechanism different from that of conventional diabetes therapeutic agents, that is, it lowers the blood glucose level by excreting it in the urine, it has an advantage that there is no burden on the pancreas due to promotion of insulin secretion. Therefore, SGLT inhibitors are expected as new hypoglycemic agents. It has been recognized that SGLT inhibitors are characterized by a decrease in blood 1,5-AG (anhydroglucitol) and an improvement in lipid metabolism in order to increase urinary sugar. Such SGLT inhibitors have been marketed one after another since 2014 as oral therapeutic agents. Further, as a food-derived SGLT inhibitor, only phlorizin (2'-glucoside floretin), which is a kind of dihydroxychalcone contained in fruits such as apples, has been discovered so far (for example, Non-Patent Document 1, Non-Patent Document 1, 2).

1,5-AG is a glucose-alcohol that resembles glucose and is absorbed from food. In vivo, it is filtered by the glomerulus of the kidney and then reabsorbed by 99.9% in the renal tubules. Therefore, the blood 1,5-AG concentration is kept constant. However, in the presence of glucose, which is very close in structure, reabsorption in the renal tubules is competitively inhibited and excreted in the urine, resulting in a decrease in blood concentration. Since it reacts very sensitively to the increase or decrease in urinary sugar excretion, it is an index of blood glucose fluctuation for a specific period or a short period of time. In particular, the presence of postprandial hyperglycemia is said to lead to a decrease in 1,5-AG. It is known that even without persistent hyperglycemia, the value becomes low due to renal failure, pregnant women, starvation, corticosteroid use, urinary excretion enhancement, α-glucosidase inhibitor use, and the like.

Diedrich, D.I. F. , Competitive inhibition of intestinal glucose glossport by phlorizin analogs, Arc. Biochem. Biophyss. , 117, 248-256 (1966). Alexander, S.A. P. H. et al. , The Concise Guide to Pharmacology 2013/14: Travelers, Brit Journal of Pharmacology 170, 1706-1796 (2013).

The present invention has been made in view of the above problems, and is a new hypoglycemic agent, a 1,5-anhydroglucitol lowering agent, a food and drink composition for lowering blood glucose, and 1,5-anhydroglucitol. It is an object of the present invention to provide a food and drink composition for reduction.

The present inventors have made extensive studies to solve the above-mentioned problems. As a result, they have found that catechins act as a 1,5-AG lowering agent, and have completed the present invention. Specifically, the present invention provides the following.

(1) The first invention of the present invention is a hypoglycemic agent containing catechins.

(2) The second invention of the present invention is the hypoglycemic agent according to claim 1, wherein the catechins contain methylated catechins in the first invention.

・・・（１）
［Ｒ_１，Ｒ_２，Ｒ_３及びＲ_４は、それぞれ独立に水素原子又はメチル基のいずれかである。ただし、Ｒ_１，Ｒ_２，Ｒ_３及びＲ_４のすべてが水素原子である場合を除く。Ｘ_１及びＸ_２は、それぞれ独立に水素原子又はヒドロキシ基のどちらかである。］ (3) In the third aspect of the present invention, in the second invention, the methylated catechin is a hypoglycemic agent represented by the general formula (1).

... (1)
[R ₁ , R ₂ , R ₃ and R ₄ are each independently either a hydrogen atom or a methyl group. However, this does not apply when all of R ₁ , R ₂ , R ₃ and R ₄ are hydrogen atoms. X ₁ and X ₂ are each independently either a hydrogen atom or a hydroxy group. ]

(4) The fourth invention of the present invention is a hypoglycemic agent in which the catechins are administered in an amount of 300 mg or more and 2000 mg or less per day in any one of the first to third inventions.

(5) The fifth aspect of the present invention is the hypoglycemic agent administered in any one of the first to fourth inventions for 50% or more of the period of 30 days or more.

(6) The sixth invention of the present invention is a blood glucose lowering food and drink composition containing the blood glucose lowering agent according to any one of the first to fourth inventions.

(7) The seventh invention of the present invention is a 1,5-anhydroglucitol lowering agent containing catechins.

(8) In the eighth aspect of the present invention, in the seventh aspect, the catechins are 1,5-anhydroglucitol lowering agents which are methylated catechins.

・・・（１）
［Ｒ_１，Ｒ_２，Ｒ_３及びＲ_４は、それぞれ独立に水素原子又はメチル基のいずれかである。ただし、Ｒ_１，Ｒ_２，Ｒ_３及びＲ_４のすべてが水素原子である場合を除く。Ｘ_１及びＸ_２は、それぞれ独立に水素原子又はヒドロキシ基のどちらかである。］ (9) In the ninth aspect of the present invention, the methylated catechin is the 1,5-anhydroglucitol lowering agent represented by the general formula (1).

... (1)
[R ₁ , R ₂ , R ₃ and R ₄ are each independently either a hydrogen atom or a methyl group. However, this does not apply when all of R ₁ , R ₂ , R ₃ and R ₄ are hydrogen atoms. X ₁ and X ₂ are each independently either a hydrogen atom or a hydroxy group. ]

(10) The tenth aspect of the present invention is the 1,5-anhydroglucitol lowering agent containing 300 mg or more and 2000 mg or less of the catechins in any one of the seventh to ninth inventions.

(11) In the eleventh invention of the present invention, in any one of the seventh to tenth inventions, 1,5-anhydro is administered for 50% or more of the period of 30 days or more. It is a glucitol lowering agent.

(12) The twelfth invention of the present invention is for reducing 1,5-anhydroglucitol containing the 1,5-anhydroglucitol lowering agent according to any one of the seventh to tenth inventions. It is a food and drink composition.

The present invention can reduce 1,5-AG after administration as a phenomenon similar to SGLT inhibitors.

Changes in blood concentration of 1,5-AG (1,5-anhydroglucitol) of effective subjects in Example 1, Comparative Example 1 and Comparative Example 2. Changes in the proportion of HbA1c in the blood of effective subjects in Example 1, Comparative Example 1 and Comparative Example 2. Changes in the proportion of glycoalbumin in the blood of effective subjects in Example 1, Comparative Example 1 and Comparative Example 2.

Hereinafter, a specific embodiment of the present invention (hereinafter referred to as “the present embodiment”) will be described in detail. The present invention is not limited to the following embodiments, and can be carried out with appropriate modifications within the scope of the object of the present invention.

≪1. Blood sugar lowering agent ≫
The hypoglycemic agent according to the present embodiment contains catechins as an active ingredient. Catechins can reduce 1,5-AG (1,5-anhydroglucitol), which is the second most abundant monosaccharide after glucose in the blood, from the blood. It is expected that blood glucose can be lowered by excreting 1,5-AG out of the body together with urine and reducing the concentration of 1,5-AG in the body. In addition, "blood glucose" refers to glucose.

More specifically, when hyperglycemic conditions occur, glucose is excreted in the urine, but at the same time, 1,5-AG, which has a chemical structure similar to that of glucose, is also excreted in the urine. Become. At this time, 1,5-AG shows a low value. Part of the glucose excreted in the urine is reabsorbed into the renal tubules, but when glucose-containing urine is reabsorbed into the renal tubules, the chemical structure is similar to that of glucose 1,5. -AG also competes and is reabsorbed into the renal tubules, resulting in increased blood glucose. This is observed in diabetic and all-diabetic cases.

On the other hand, catechins can lower the values of 1,5-AG without changing the Hb1Ac and glycoalbumin levels. It enhances urinary excretion, increases 1,5-AG excretion and decreases blood 1,5-AG, thereby inhibiting reabsorption of glucose and 1,5-AG into the renal tubules. Can be done. Such an inhibitory effect is similar to the effect of SGLT inhibition. As for catechins, phloretin, which is an aglycone of phlorizin contained in apples, is the same flavonoid. Specifically, catechins belong to flavanols and phloretin belongs to chalcones, and both have the same structure of the A ring. The B ring also differs in the number of OH by only one.

The total content of catechins in the hypoglycemic agent is not particularly limited, but is preferably an effective amount, specifically, preferably 300 mg or more, more preferably 400 mg or more, and 500 mg or more. Is more preferable. By containing 300 mg or more, a sufficient blood glucose lowering effect can be obtained. On the other hand, the upper limit is preferably 2000 mg or less, more preferably 1500 mg or less, and further preferably 1000 mg or less. If it is 1000 mg or less, when it is added to a food or drink, the taste or flavor of the food or drink is less affected. When a plurality of the formulated hypoglycemic agents of the present invention are administered, the content of catechins in each individual pharmaceutical product may be divided by the number of the pharmaceutical products. For example, when three pharmaceuticals of a hypoglycemic agent are administered, the total content of catechins in each of the pharmaceuticals may be 100 mg, and a total of 300 mg may be administered. For example, when orally administered alone without being added to foods and drinks, the larger the amount of catechins, the more astringent it feels, but by administering it in divided doses, the astringency can be suppressed.

The total dose of catechins is not particularly limited, but is preferably 300 mg or more, more preferably 400 mg or more, and even more preferably 500 mg or more per day. By containing 300 mg or more, a sufficient blood glucose lowering effect can be obtained. On the other hand, as the upper limit, the daily dose is preferably 2000 mg or less, more preferably 1500 mg or less, and further preferably 1000 mg or less. If the amount is 1000 mg or less, the taste and flavor of the food or drink will not be affected when blended in the food or drink.

The catechins are not particularly limited as long as they are catechins, methylated catechins or derivatives thereof, but it is preferable to use methylated catechins among them. By using methylated catechin, a particularly excellent blood glucose lowering effect can be obtained.

Here, methylated catechin is a general term for a group of compounds in which a part of the hydroxyl group of catechin or a catechin derivative is methoxylated. Specifically, for example, epigalocatechin-3-O- (3-O-methyl) gallate (hereinafter, may be referred to as EGCG3 "Me)" and epicatechin-3-O- (3-O-methyl) gallate. (Hereinafter, sometimes referred to as ECG3 "Me), Epicatechin-3-O- (4-O-methyl) gallate (hereinafter, sometimes referred to as ECG4" Me), Epi-gallocatechin-3-O- (4-). O-methyl) gallate (hereinafter sometimes referred to as EGCG4 "Me), galocatechin-3-O- (3-O-methyl) gallate (hereinafter sometimes referred to as GCG3" Me), catechin-3-O- (hereinafter sometimes referred to as GCG3 "Me). 3-O-methyl) gallate (hereinafter sometimes referred to as CG3 "Me), catechin-3-O- (4-O-methyl) gallate (hereinafter sometimes referred to as CG4" Me), or catechin-3. -O- (4-O-methyl) gallate (hereinafter sometimes referred to as GCG4 "Me), epigalocacatechin-3-O- (3,5-O-dimethyl) gallate, epigallocatechin-3-O- (3,4-O-dimethyl) gallate, epicatechin-3-O- (3,5-O-dimethyl) gallate, epicatechin-3-O- (3,4-O-dimethyl) gallate and their opposite sex Examples include catechins.

・・・（１）
［Ｒ_１，Ｒ_２，Ｒ_３及びＲ_４は、それぞれ独立に水素原子又はメチル基のいずれかである。ただし、Ｒ_１，Ｒ_２，Ｒ_３及びＲ_４のすべてが水素原子である場合を除く。Ｘ_１及びＸ_２は、それぞれ独立に水素原子又はヒドロキシ基のどちらかである。］ Further, as the methylated catechin, it is preferable to use a compound having a chemical structure represented by the general formula (1). By using a methylated catechin having such a structure, a particularly excellent blood glucose lowering effect can be obtained.

... (1)
[R ₁ , R ₂ , R ₃ and R ₄ are each independently either a hydrogen atom or a methyl group. However, this does not apply when all of R ₁ , R ₂ , R ₃ and R ₄ are hydrogen atoms. X ₁ and X ₂ are each independently either a hydrogen atom or a hydroxy group. ]

The content of the methylated catechin in the hypoglycemic agent is not particularly limited, but is preferably 20 mg or more, more preferably 30 mg or more, still more preferably 40 mg or more. A sufficient blood glucose lowering effect can be obtained by containing 30 mg or more. On the other hand, the upper limit is preferably 100 mg or less, more preferably 80 mg or less, and even more preferably 70 mg or less. If the amount is 100 mg or less, the taste and flavor of the food or drink will not be affected when blended in the food or drink.

The dose of methylated catechin is not particularly limited, but is preferably 20 mg or more, more preferably 30 mg or more, and even more preferably 40 mg or more per day. A sufficient blood glucose lowering effect can be obtained by containing 20 mg or more. On the other hand, as the upper limit, the daily dose is preferably 100 mg or less, more preferably 80 mg or less, and even more preferably 70 mg or less. If the amount is 100 mg or less, the taste and flavor of the food or drink will not be affected when blended in the food or drink.

Further, the catechins other than the methylated catechin are not particularly limited. Specific examples thereof include (+)-catechin, epicatechin, epigallocatechin gallocatechin, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, catechin gallate and the like.

The hypoglycemic agent of the present invention may or may not contain other components other than the catechins described above. As other components, for example, polyphenol components other than catechins, caffeine (for example, 50 to 300 mg), and components usually used for formulation (components of excipients, etc.) can be contained. Even if caffeine is contained, the above-mentioned blood glucose lowering effect is not suppressed. In addition, when blended in foods and drinks, the taste and flavor of the foods and drinks are less affected.

The method for preparing or producing the hypoglycemic agent is not particularly limited, but specifically, for example, Benifuuki, Benifuji, Benihomare, Asagiri, Yaeho, Shigase, Yutaka Midori. , Kanaya Midori, Okumusashi, Okuyutaka, Shunmei, Ryofu, Seishin Daipan, Seishin Karyu, Ooba Karyu, Beni Hikari, Minami Sayaka, Yamakai, Yamato Midori, Karabeni, Kashun , Sofu, Okumidori, Saemidori, Saint Rouge and other tea leaves can be used as they are or dried. Further, these dried tea leaves can be extracted with water or various solvents, and the obtained extract can be used. Furthermore, it can also be synthesized by an organic chemical synthesis method. The obtained extract and the synthesized compound can be appropriately purified.

The extraction temperature is not particularly limited and can be appropriately adjusted according to the boiling point of the solvent, the vapor pressure and the like. Specifically, for example, 10 ° C to 100 ° C is desirable when water is used, and 10 ° C to 40 ° C is desirable when ethanol and methanol are used. The extraction time is preferably in the range of 10 seconds to 24 hours.

Specifically, for example, water, alcohols (methanol, ethanol, propanol, isopropanol, butanol, isobutanol, etc.), ethers (ethyl ether, dioxane), and ketones (acetone, etc.) are preferably used as the extraction solvent. , Water, ethanol or a mixed solvent of water and ethanol is more preferred.

The extract obtained by the extraction can be used as it is. It can also be purified by a purification method. Specific examples of such purification methods include liquid-liquid distribution, thin layer chromatography, adsorption column chromatography, distribution column chromatography, gel filtration column chromatography, ion exchange column chromatography, and electrophoresis. High-speed liquid chromatography and the like can be used. In addition, these purification methods can be combined.

The form of the hypoglycemic agent is not particularly limited, and may be, for example, a form of dried tea leaves or a powder of dried tea leaves. In addition, the extract or synthetic product can be in the form of a solid substance such as powder. Further, those solids and the like can also be in the form of tablets. Further, it can be extracted or dissolved to form a solution.

The method of administration is not particularly limited, but is preferably taken orally, for example.

The administration period of the hypoglycemic agent is not particularly limited, but is preferably 30 days or longer, more preferably 40 days or longer, and even more preferably 50 days or longer. By administering the blood glucose lowering agent for a long period of 30 days or more, the blood glucose level can be effectively lowered. The upper limit of the administration period of the hypoglycemic agent may be set to, for example, 1 year or less (6 months or less, 3 months or less, etc.). In particular, it is preferable that the hypoglycemic agent is administered at the total daily dose of the above-mentioned catechins for a period of 30 days or more.

The frequency of administration of the hypoglycemic agent is not particularly limited, but it is preferably administered for 30% or more of the above-mentioned administration periods, more preferably 40% or more, and 50%. It is more preferable to administer for the above number of days. By administering a blood glucose lowering agent for 30% or more days, the blood glucose level can be effectively lowered. The upper limit of the administration frequency of the hypoglycemic agent may be set to, for example, 90% or less.

≪2.1,5-Anhydroglucitol lowering agent≫
The 1,5-anhydroglucitol lowering agent according to the present embodiment contains catechins as an active ingredient. As the 1,5-anhydroglucitol lowering agent, the same ones as those described above can be used. The same applies to the manufacturing method and usage. As mentioned above, catechins can excrete 1,5-anhydroglucitol out of the body and reduce the concentration of 1,5-anhydroglucitol in the body. Therefore, it may be used to obtain the effect directly or indirectly expected (for example, the blood glucose lowering effect) by lowering the amount of 1,5-anhydroglucitol in the blood.

≪3. Eating and drinking composition for lowering blood sugar ≫
The food and drink composition for lowering blood glucose according to the present embodiment contains the above-mentioned hypoglycemic agent, and contains catechins contained in the hypoglycemic agent as an active ingredient. By orally ingesting such a food and drink composition, the blood glucose after ingestion can be lowered due to the hypoglycemic effect of catechins contained in the hypoglycemic agent.

The food containing the hypoglycemic agent is not particularly limited. Specifically, for example, it can be added as an additive to foods for specified health use, foods with functional claims, foods for special use, dietary supplements, foods with nutritional function, health foods and the like. It can also be added to general foods such as confectionery, bread, noodles, processed soybean products, dairy products, processed egg products, paste products, fats and oils, and seasonings.

The beverage to which the blood glucose lowering agent can be blended is not particularly limited. Specifically, for example, it can be added as an additive to foods for specified health use, foods with functional claims, foods for special use, nutritional supplements, beverages as nutritionally functional foods, and other nutritional beverages. It can also be added to health drinks, various health teas, and other general soft drinks and tea drinks. From the viewpoint of ease of ingestion, it is preferable to add it to a beverage.

<< 4.1,5-Anhydroglucitol-lowering food and drink composition >>
The food and drink composition for lowering 1,5-anhydroglucitol according to the present embodiment contains the above-mentioned 1,5-anhydroglucitol lowering agent and contains 1,5-anhydroglucitol. The active ingredient is catechins contained in the lowering agent. By orally ingesting such a food and drink composition, blood glucose after ingestion is due to the 1,5-anhydroglucitol lowering effect of catechins contained in the 1,5-anhydroglucitol lowering agent. Can be reduced.

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

A total of 119 subjects with high visceral fat were randomly divided into 39 in group 1 (Example 1), 40 in group 2 (comparative example 1), and 40 in group 3 (comparative example 2). .. Subjects were given a different lunch for each group for lunch for 57 days on weekdays (Monday to Friday, excluding Saturdays, Sundays and public holidays). Subjects who were able to take lunch for 80% or more of the total 57 days of the test period (about 54% of the 12 weeks including Saturdays, Sundays, and holidays) were considered as effective subjects. Here, this bento consists of rice as a staple food, two main dishes and side dishes as side dishes, and tea beverages. For each group, lunch boxes using functional foods were supplied to any of the staple food, side dishes and tea, and their effects were confirmed. Table 1 shows the contents of the lunch boxes ingested by the subjects in each group. In addition, Table 2 shows the nutritional value contained in the lunch boxes ingested by the subjects in each group.

[Example 1]
For the subjects in Group 1, white rice was used as rice, side dishes using ordinary vegetables were used as side dishes, and Benifuuki green tea extract was freeze-dried as a tea beverage. Powdered green tea (drinking 3 packets after meals; per day) , Total catechin 670 mg, methylated catechin 50 mg, caffeine 125 mg / day). Among the subjects in Group 1, 31 subjects were able to take the lunch box for 80% or more of the total number of days during the test period. Table 3 shows the contents of various catechins in the powdered green tea ingested by the effective subjects of Group 1 per day.

[Comparative Example 1]
The subjects in Group 2 were fed white rice as rice, side dishes using functional vegetables rich in lutein, which is a kind of carotenoid, as side dishes, and barley tea containing no catechins as tea beverages. Among the subjects in Group 2, 37 subjects were able to take the lunch box for 80% or more of the total number of days during the test period.

[Comparative Example 2]
For the subjects in Group 3, white rice and brown rice containing 50% of barley containing β-glucan were alternately added as rice so that they would be served every other day, and side dishes using ordinary vegetables as side dishes were used as tea beverages. Barley tea containing no was ingested. Among the subjects in Group 3, 35 subjects were able to take the lunch box for 80% or more of the total number of days during the test period.

<Measurement result>
At the start of ingestion, 6 weeks after the start of ingestion and 12 weeks after the start of ingestion, the blood 1,5-AG (anhydroglucitol) concentration of the effective subject, the ratio of HbA1c to the total amount of hemoglobin, and glycoalbumin to the total amount of albumin. The ratio of was measured.

FIG. 1 shows changes in blood concentrations of 1,5-AG (anhydroglucitol) of subjects in Example 1, Comparative Example 1 and Comparative Example 2. As described above, in Example 1 in which the subject continued to ingest catechin, 1,5-AG of the subject was significantly higher than in Comparative Example 1 and Comparative Example 2 in which the subject continued to ingest barley tea containing no catechins. It was found to decrease (p <0.001). As a result of investigating the relationship between the lowering effect of 1,5-AG and the daily number of steps of the effective subject of Example 1, such a blood glucose lowering effect is particularly effective for subjects having 10,000 or more steps per day. Was remarkable in.

In Comparative Example 1, no significant difference was found in the amount of 1,5-AG of the effective subjects in Group 2. Further, in Comparative Example 2, 1,5-AG of the effective subjects in Group 3 increased from 6 to 12 weeks after the start of ingestion.

FIG. 2 shows changes in the proportion of HbA1c in the blood of effective subjects in Example 1, Comparative Example 1 and Comparative Example 2. In addition, FIG. 3 shows changes in the proportion of glycoalbumin in the blood of effective subjects in Example 1, Comparative Example 1 and Comparative Example 2. In Example 1 in which the subject continued to ingest catechin, the proportion of HbA1c and the proportion of glycoalbumin did not increase between 6 and 12 weeks from the start of ingestion. On the other hand, in Comparative Example 1, the proportion of glycoalbumin did not increase from 6 to 12 weeks after the start of ingestion, but the proportion of HbA1c increased. Further, in Comparative Example 2, the proportion of HbA1c decreased but the proportion of glycoalbumin increased between 6 and 12 weeks after the start of ingestion.

It is generally known that the cause of the decrease in blood 1,5-AG concentration is either an increase in blood glucose or an SGLT inhibitory effect. Here, if the 1,5-AG concentration decreases due to an increase in blood glucose, the proportions of HbA1c in which glucose is bound to hemoglobin and glycoalbumin in which glucose is bound to albumin increase. As can be seen from FIGS. 2 and 3, in Example 1, HbA1c and glycoalbumin were found to have decreased blood 1,5-AG concentrations between 6 and 12 weeks after the start of ingestion. Since the ratio did not increase, it was found that the intake of catechins increased the amount of urinary excretion, resulting in a blood glucose lowering effect.

Claims (3)

1,5-Anhydroglucitol containing benifuuki tea extract for administering methylated catechins for 80% or more of the period of 30 days or more, 20 mg or more and 100 mg or less per day. Lowering agent. The 1,5-anhydroglucitol lowering agent according to claim 1, wherein the methylated catechin is a compound represented by the general formula (1).

[R ₁ , R ₂ , R ₃ and R ₄ are each independently either a hydrogen atom or a methyl group. However, this does not apply when all of R ₁ , R ₂ , R ₃ and R ₄ are hydrogen atoms. X ₁ and X ₂ are each independently either a hydrogen atom or a hydroxy group. ] A food and drink composition for reducing 1,5-anhydroglucitol containing the 1,5-anhydroglucitol lowering agent according to claim 1 or 2.

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