WO2016133155A1

WO2016133155A1 - α-GLUCOSIDASE INHIBITOR

Info

Publication number: WO2016133155A1
Application number: PCT/JP2016/054688
Authority: WO
Inventors: 寿栄鈴木; 惇紀吉田
Original assignee: サントリーホールディングス株式会社
Priority date: 2015-02-19
Filing date: 2016-02-18
Publication date: 2016-08-25
Also published as: JP6661597B2; TW201642895A; JPWO2016133155A1

Abstract

Provided are: an α-glucosidase inhibitor; a dipeptide-containing food or beverage; a use of said inhibitor for inhibiting α-glucosidase; and a method for inhibiting α-glucosidase. It was discovered that a specific cyclic or straight-chain dipeptide or salt thereof exhibits an α-glucosidase inhibitory effect. The present invention provides an effective new means that contributes to the suppression of an increase in blood glucose level after eating and the prevention or improvement of diabetes.

Description

α-Glucosidase inhibitor

The present invention relates to an α-glucosidase inhibitor. More specifically, an α-glucosidase inhibitor, an α-glucosidase-inhibiting food and drink, a specific cyclic or linear dipeptide having an amino acid as a constituent unit or a salt thereof as an active ingredient, a specific for inhibiting α-glucosidase The invention relates to the use of cyclic or linear dipeptides or salts thereof and to methods for inhibiting α-glucosidase.

In the modern society, the number of diabetics or their reserves is increasing due to lifestyle changes. Diabetes is a disease caused by abnormal sugar metabolism, and various complications (diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, etc.) are caused by pathologically increased blood glucose levels (glucose concentration in the blood). ) Is a disease at risk. In particular, since non-insulin dependent diabetes patients account for 90% or more of diabetes onset, their improvement and prevention are strongly desired.

In the treatment, improvement, or prevention of diabetes, it is important to appropriately control the blood glucose level. Polysaccharides such as starch, oligosaccharides, or sucrose ingested through meals or the like are broken down into free glucose by α-glucosidase present in the small intestinal epithelium. Free glucose is absorbed from the small intestine and supplied into the blood via the liver, which raises the blood sugar level. However, diabetics cannot reduce elevated blood sugar levels. Therefore, in order to appropriately control the blood glucose level of a diabetic patient, it is important to lower the high blood glucose level. One method for lowering blood glucose level is to inhibit the α-glucosidase activity present in the small intestine epithelium, that is, to inhibit or delay the production and absorption of glucose in the digestive tract. If the decomposition and absorption of diet-derived sugar can be suppressed healthily and easily by inhibiting α-glucosidase activity, it is effective for the prevention and promotion of diabetes and related diseases.

Under such circumstances, “dipeptides” in which two amino acids are combined are attracting attention as functional substances. Dipeptides are capable of adding physical properties and new functions not found in simple amino acids, and are expected to have a range of applications beyond amino acids. As active ingredients such as pharmaceuticals, health maintenance and lifestyle habits are expected. It is used for the prevention and improvement of diseases.

In recent years, diketopiperazine derivatives, which are cyclic dipeptides having a cyclic structure formed by dehydration condensation of an amino group and a carboxyl group present at the end of a dipeptide, have been developed. The cyclic dipeptide has been reported to have various physiological activities, and demand is expected to expand in the medical and pharmacological fields. For example, Patent Document 1 reports that a cyclic dipeptide having a 2,5-diketopiperazine structure has an antidepressant action, a learning motivation improving action, and the like. Non-patent document 1 describes that cyclohistidylproline [Cyclo (His-Pro)] reduces body temperature, suppresses appetite, suppresses prolactin secretion, It has been described that it exhibits many physiological activities such as hormone-like effects such as promoting hormone secretion, and it has been reported that cycloleucylglycine [Cyclo (Leu-Gly)] has an effect of improving memory function.

Non-patent document 2 discloses that cyclotryptophanylproline [Cyclo (Trp-Pro)] has anticancer activity, cyclohistidylproline [Cyclo (His-Pro)] and cycloglycylproline [Cyclo (Gly- Pro)), anti-microbial action on cyclohistidylproline [Cyclo (His-Pro)], neuroprotective action on cycloglycylproline [Cyclo (Gly-Pro)], improvement on memory function, cyclotryptophanylproline [Cyclo (Trp-Pro)] and cyclophenylalanylproline [Cyclo (Phe-Pro)] have been described as having action as biological herbicides. Non-Patent Document 3 describes that cyclohistidylproline [Cyclo (His-Pro)] improves the diabetic condition of rats when used in combination with zinc. Patent Document 2 reports the α-glucosidase inhibitory action of the linear dipeptide threonyltyrosine (Thr-Tyr), but the α-glucosidase inhibitory action of the corresponding cyclic dipeptide [Cyclo (Thr-Tyr)]. There are no reports.

Special table 2012-517998 gazette JP 2010-047513 A

An object of the present invention is to provide an α-glucosidase inhibitor, the use of the agent for inhibiting α-glucosidase, and a method for inhibiting α-glucosidase. Another object of the present invention is to provide a food or drink for α-glucosidase inhibition.

As a result of intensive studies, the present inventors have found that a specific cyclic dipeptide or a salt thereof has a remarkable α-glucosidase inhibitory action. Furthermore, the present inventors have found that a specific linear dipeptide or a salt thereof has an α-glucosidase inhibitory action, and have completed the present invention.

That is, the present invention relates to the following, but is not limited thereto.
(1) An α-glucosidase inhibitor containing as an active ingredient a cyclic dipeptide having an amino acid as a structural unit or a salt thereof,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and one or more selected from the group consisting of cyclophenylalanylproline [Cyclo (Phe-Pro)], the α-glucosidase inhibitor.
(2) Cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)] , Cycloisoleucil threonine [Cyclo (Ile-Thr)], cycloasparaginyl tyrosine [Cyclo (Asn-Tyr)], cycloisoleucil glycine [Cyclo (Ile-Gly)], cyclomethionyl leucine [Cyclo ( Met-Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucilleucine (Cyclo (Ile-Leu)), cyclotyrosyltyrosine (Cyclo (Tyr-Tyr)), cyclophenylalanyltyrosine (Cyclo (Phe-Tyr)), cycloglycylphenylalanine (Cyclo (Gly-Phe)), cyclo Histidylphenylalanine (Cyclo (His-Phe)), cyclotri Tophanyltyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyltyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)] Cyclotryptophanyl threonine [Cyclo (Trp-Thr)], cycloalanyl tyrosine [Cyclo (Ala-Tyr)], cyclothreonyl tyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe -Phe)], cycloleucyltryptophan [Cyclo (Leu-Trp)], and cyclotryptophanylglutamic acid [Cyclo (Trp-Glu)], one or more selected from the group ( The α-glucosidase inhibitor according to 1).
(3) The α-glucosidase inhibitor according to (1), wherein the cyclic dipeptide or a salt thereof includes three or more selected from the group described in (1).
(4) The α-glucosidase inhibitor according to (2), wherein the cyclic dipeptide or a salt thereof includes three or more selected from the group described in (2).
(5) The α-glucosidase inhibitor according to any one of (1) to (4), which is used for suppressing absorption of dietary sugar.
(6) The α-glucosidase inhibitor according to any one of (1) to (4), which is used for suppressing an increase in blood glucose level.
(7) The α-glucosidase inhibitor according to any one of (1) to (4), which is used for diabetes prevention.
(8) The α-glucosidase inhibitor according to any one of (1) to (4), which is used for suppressing digestion and absorption of carbohydrates.
(9) The α-glucosidase inhibitor according to any one of (1) to (8), wherein the cyclic dipeptide having an amino acid as a structural unit or a salt thereof is obtained from an animal or plant derived peptide.
(10) The α-glucosidase inhibitor according to (9), wherein the animal or plant derived peptide is soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide.
(11) An α-glucosidase-inhibiting food / beverage product comprising, as an active ingredient, a cyclic dipeptide having an amino acid as a structural unit or a salt thereof,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and one or more selected from the group consisting of cyclophenylalanylproline [Cyclo (Phe-Pro)].
(12) Cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)]. , Cycloisoleucil threonine [Cyclo (Ile-Thr)], cycloasparaginyl tyrosine [Cyclo (Asn-Tyr)], cycloisoleucil glycine [Cyclo (Ile-Gly)], cyclomethionyl leucine [Cyclo ( Met-Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucilleucine (Cyclo (Ile-Leu)), cyclotyrosyltyrosine (Cyclo (Tyr-Tyr)), cyclophenylalanyltyrosine (Cyclo (Phe-Tyr)), cycloglycylphenylalanine (Cyclo (Gly-Phe)), cyclo Histidylphenylalanine (Cyclo (His-Phe)), cycloto Ptophanyltyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyltyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)] Cyclotryptophanyl threonine [Cyclo (Trp-Thr)], cycloalanyl tyrosine [Cyclo (Ala-Tyr)], cyclothreonyl tyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe -Phe)], cycloleucyltryptophan [Cyclo (Leu-Trp)], and cyclotryptophanylglutamic acid [Cyclo (Trp-Glu)], one or more selected from the group ( The food or drink as described in 11).
(13) The food or drink according to (11), wherein the cyclic dipeptide or a salt thereof includes three or more selected from the group described in (11).
(14) The food or drink according to (12), wherein the cyclic dipeptide or a salt thereof includes three or more selected from the group described in (12).
(15) The total amount of the cyclic dipeptide or its salt is 1.0 × 10 to 2.0 × 10 ⁵ ppm, and the content of each of the cyclic dipeptide or its salt is 1.0 × 10 to 2.0 × 10 The food or drink according to any one of (11) to (14), which is ⁵ ppm.
(16) The food or drink according to any one of (11) to (15), wherein the cyclic dipeptide having an amino acid as a structural unit or a salt thereof is obtained from an animal or plant-derived peptide.
(17) The food or drink according to (16), wherein the animal or plant derived peptide is soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide.
(18) The food or drink according to any one of (11) to (17), which is labeled with a function exhibited by α-glucosidase inhibition.
(19) The function display is selected from the group consisting of “smooth sugar absorption”, “smooth digestive absorption of carbohydrates”, “suppresses postprandial blood sugar rise”, and “prevents diabetes” The food and drink as described in (18).
(20) Use of a cyclic dipeptide having an amino acid as a structural unit or a salt thereof for inhibiting α-glucosidase,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and cyclophenylalanylproline [Cyclo (Phe-Pro)], wherein the use is one or more.
(21) A method for inhibiting α-glucosidase, which uses, as an active ingredient, a cyclic dipeptide having amino acid as a structural unit or a salt thereof,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and one or more selected from the group consisting of cyclophenylalanylproline [Cyclo (Phe-Pro)].
(22) an α-glucosidase inhibitor containing, as an active ingredient, a linear dipeptide having an amino acid as a structural unit or a salt thereof,
The α-glucosidase inhibitor, wherein the linear dipeptide or a salt thereof includes phenylalanylphenylalanine (Phe-Phe) and / or valylmethionine (Val-Met).
(23) An α-glucosidase-inhibiting food or drink containing a linear dipeptide having amino acid as a structural unit or a salt thereof as an active ingredient,
The food or beverage product, wherein the linear dipeptide or a salt thereof contains phenylalanylphenylalanine (Phe-Phe) and / or valylmethionine (Val-Met).
(24) The food or drink according to (23), which is labeled with a function exhibited by α-glucosidase inhibition.
(25) The function display is selected from the group consisting of “smooth sugar absorption”, “smooth digestive absorption of carbohydrates”, “suppresses postprandial blood glucose rise”, and “prevents diabetes” Food / beverage products as described in (24).

In the present invention, α-glucosidase can be inhibited by using a specific cyclic or linear dipeptide or a salt thereof. The α-glucosidase inhibitor of the present invention promotes the decomposition and / or absorption suppression of dietary sugar, suppresses the digestion and absorption of carbohydrates, promotes the decrease and / or increase of blood glucose level, and prevents, improves or treats diabetes Provide new means to contribute to

In addition, according to the present invention, it is possible to provide an α-glucosidase-inhibiting food or drink containing a specific cyclic or linear dipeptide or a salt thereof.

FIG. 1 shows the α-glucosidase inhibition rate of cyclic dipeptides Cyclo (Thr-Tyr) and Cyclo (Phe-Phe) and linear dipeptide Phe-Phe. FIG. 2 shows the inhibition rate of cyclic dipeptide Cyclo (Met-Val) and linear dipeptides Met-Val and Val-Met α-glucosidase.

1. α-Glucosidase and α-Glucosidase Inhibition In this specification, “α-glucosidase” refers to an enzyme that decomposes disaccharides such as maltose produced by digestion of starch and converts it into glucose. Specifically, α-glucosidase is an enzyme that catalyzes the hydrolysis reaction of α-1,4-glucoside bonds of disaccharides. Most organisms have this enzyme, especially in humans, it is expressed as a membrane enzyme in small intestinal mucosal epithelial cells. As described above, the disaccharide is decomposed into glucose by α-glucosidase, and the glucose is absorbed into the blood from the small intestine, thereby increasing the blood glucose level. Therefore, inhibition of α-glucosidase reduces the amount of glucose produced by the decomposition of the disaccharide, and as a result, the increase in blood glucose level is suppressed.

In the present invention, α-glucosidase inhibition refers to inhibition of α-glucosidase present in small intestinal mucosal epithelial cells. Thereby, decomposition | disassembly and absorption of the carbohydrate derived from a food are suppressed and / or delayed, and the raise of a blood glucose level is suppressed. The α-glucosidase activity can be measured according to a known method. For example, the absorbance of 4-nitrophenol produced by the reaction with α-glucosidase using 4-nitrophenyl-α-glucopyranoside (NPG) as a substrate is measured. By measuring, α-glucosidase activity can be measured. The α-glucosidase inhibitory activity can also be expressed by a conventional method by expressing the sample amount IC50 (50% inhibitory concentration) that gives 50% inhibition to the α-glucosidase activity.

2. Cyclic Dipeptide and Linear Dipeptide In the present invention, the dipeptide may be a cyclic dipeptide or a linear dipeptide. In the present specification, a cyclic dipeptide is a dipeptide having a diketopiperazine structure produced by dehydration condensation of an amino group and a carboxyl group of an amino acid, wherein the amino acid is a structural unit. In the present specification, cyclic dipeptides or salts thereof may be collectively referred to simply as cyclic dipeptides. Further, in this specification, as long as the amino acid composition of the cyclic dipeptide is the same, any order may be given, for example, [Cyclo (Met-Val)] and [Cyclo (Val-Met)] Represent the same cyclic dipeptide.

In this specification, a linear dipeptide is characterized in that an amino acid is a structural unit, and the amino group of one amino acid and the carboxyl group of the other amino acid are linked by one peptide bond by dehydration condensation. It refers to a dipeptide. In the present specification, linear dipeptides or salts thereof may be collectively referred to simply as linear dipeptides.

Cyclic dipeptides have two amino acid terminal moieties attached via an amide bond, so they are more lipophilic than linear dipeptides that have a polar carboxyl group or amino group exposed at the molecular end. Is characterized by high. Therefore, cyclic dipeptides are superior in gastrointestinal permeability and membrane permeability compared to linear dipeptides.

In the present specification, the cyclic or linear dipeptide salt refers to any pharmacologically acceptable salt (including inorganic salts and organic salts) of the cyclic or linear dipeptide. Or sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt, hydrochloride, sulfate, nitrate, phosphate, organic acid salt (acetate, citrate, maleate, malate of linear dipeptide Oxalate, lactate, succinate, fumarate, propionate, formate, benzoate, picrate, benzenesulfonate, trifluoroacetate, etc.). It is not limited. Cyclic or linear dipeptide salts can be readily prepared by those skilled in the art by any method known in the art.

The linear dipeptide used in the present invention can be prepared according to a method known in the art. For example, a linear dipeptide having an arbitrary sequence may be prepared by peptide synthesis, or may be synthesized using microbial fermentation or an enzyme. The protein is subjected to enzymatic treatment or heat treatment to be decomposed, and then separated and purified. May be prepared. Moreover, you may use a commercial item or a synthetic thing for the linear dipeptide of this invention.

The cyclic dipeptide used in the present invention can be prepared according to a method known in the art. For example, it may be produced by a chemical synthesis method, an enzymatic method, or a microbial fermentation method, or may be synthesized by dehydration and cyclization of a linear peptide. JP 2003-252896 A, Journal of Peptide や Science, 10, 737-737, 2004. For example, animal and plant-derived peptides obtained by subjecting ingredients containing animal and plant-derived proteins to enzyme treatment or heat treatment to lower the molecular weight of the proteins, such as soybean peptides, tea peptides, malt peptides, rice peptides, chicken peptides, milk peptides A processed product obtained by further heat-treating placenta peptide or collagen peptide can be preferably used.

In the present invention, the cyclic or linear dipeptide having an amino acid as a structural unit is obtained from a heat-treated product of soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide. May be. In addition, the cyclic or linear dipeptide in the present invention may be obtained by a one-step process in which heat treatment is applied to a component containing a protein derived from animals and plants. For example, it may be obtained by heat-treating soy protein, tea protein, malt protein, rice protein, milk protein, placenta protein, or collagen protein. In addition, soy peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, specific cyclic or linear dipeptide in heat-treated product of collagen peptide, or soy protein, tea protein, malt protein, rice If the specific cyclic or linear dipeptide in the heat-treated product of protein, milk protein, placenta protein, or collagen protein is less than the specific content, other animal or plant derived peptides may be used for the specific cyclic or linear dipeptide to be deficient. It can also be added as appropriate using commercially available products or synthetic products.

3. Animal and plant derived peptides 3-1. Soybean peptide As used herein, “soybean peptide” refers to a low molecular weight peptide obtained by subjecting soy protein to enzyme treatment or heat treatment to lower the molecular weight of the protein. Soybeans (scientific name: Glycine max) used as a raw material can be used without restriction of varieties and production areas, and can also be used in processed products such as pulverized products.

A heat-treated soybean peptide containing a cyclic or linear dipeptide at a high concentration can be obtained by heat-treating the soybean peptide. Specifically, for example, soybean peptide can be prepared by heating at 40 to 150 ° C. for 5 minutes to 120 hours. If necessary, the obtained heat-treated product may be subjected to treatments such as filtration, centrifugation, concentration, ultrafiltration, lyophilization, and powdering.

3-2. Tea peptide As used herein, “tea peptide” refers to a low molecular weight peptide derived from tea obtained by subjecting a tea (including tea leaves or tea husk) extract to enzyme treatment or heat treatment to lower the protein. . As a tea leaf used as an extraction raw material, a tea leaf (scientific name: Camellia sinensis) manufactured tea leaf leaf, stem, etc. that can be extracted and used can be used. Also, the form is not limited to large leaves or powders. The harvest time of tea leaves can also be selected appropriately according to the desired flavor.

The tea extract used in the present invention preferably has a low by-product content and has a good flavor. From this flavor point of view, the raw tea leaves are steamed non-fermented tea (green tea) such as Sencha, Bancha, Hojicha, Gyokuro, Kabusecha, and Kochacha, Ureshino tea, Aoyagi tea, various Chinese tea, etc. It is preferable to use unfermented tea such as tea.

3-3. Malt peptide As used herein, the term “malt peptide” refers to a malt-derived low molecular weight peptide obtained by subjecting an extract obtained from malt or a pulverized product thereof to enzymatic treatment or heat treatment to lower the molecular weight of the protein. . Although the malt peptide used as a raw material can be used without restriction of varieties and production areas, barley malt obtained by germinating barley seeds is particularly preferably used. For barley malt, it is practical and efficient to remove the skin and separate and use a fraction having a high protein content. For example, the fraction having a high protein content may be a method in which malt is gradually shaved from the surface, the husk is removed, and then a fraction containing a large amount of protein such as an aleurone layer and endosperm is shaved off.

3-4. Rice peptide As used herein, “rice peptide” refers to rice, brown rice, a part or pulverized product thereof, and an extract obtained from oils and fats obtained from rice (rice bran oil or rice germ oil). Or a low molecular weight peptide derived from rice obtained by heat treatment to reduce the molecular weight of the protein. The rice peptide used as a raw material can be used without limitation of the variety or production area.

3-5. Chicken peptide As used herein, the term “chicken peptide” refers to a chicken-derived low molecular weight peptide obtained by reducing the molecular weight of a protein obtained from chicken or a part of chicken tissue. For example, as described in WO2011 / 077759 Can be obtained.

3-6. Milk peptide As used herein, “milk peptide” is a product obtained by decomposing milk protein, which is a component derived from natural milk, into a molecule in which at least several amino acids are bound. More specifically, it is obtained by hydrolyzing milk protein such as whey (whey protein) or casein with an enzyme such as proteinase, and filtering and sterilizing and / or concentrating and drying the filtrate. Examples include whey peptides and casein peptides.

3-7. The placenta peptide placenta is the placenta of mammals and has been used as a health food, cosmetics, and pharmaceutical material in recent years because of its excellent functionality. As used herein, “placenta peptide” refers to a placenta that has been solubilized and reduced in molecular weight by enzyme treatment or subcritical treatment. In addition, although different from the original meaning, extracts obtained from plant placenta are used in health foods, cosmetics, etc. as having a physiological effect equivalent to placenta derived from placenta. be called. The placenta of the plant is the part of the pistil where the ovule is attached. The “placenta peptide” as used in the present invention includes those obtained by subjecting plant placenta to enzyme treatment or subcritical treatment, solubilization and low molecular weight.

3-8. Collagen peptide As used herein, the term “collagen peptide” refers to a low molecular peptide obtained by subjecting collagen or a pulverized product thereof to enzymatic treatment or heat treatment to lower the molecular weight of collagen. Collagen is a major protein in animal connective tissue and is the most abundant protein in mammalian bodies including humans.

A composition containing a large amount of cyclic or linear dipeptide can be obtained by heat treating the collagen peptide. Specifically, for example, the collagen peptide is heated at a temperature higher than 100 ° C., preferably 100 to 170 ° C., more preferably 110 to 150 ° C., and still more preferably 120 to 140 ° C., for 5 minutes to 120 hours. Preferably, it can be prepared by heating for 3 to 10 hours. If necessary, the obtained heat-treated product may be subjected to treatments such as filtration, centrifugation, concentration, ultrafiltration, lyophilization, and powdering.

4). α-Glucosidase inhibitor 4-1. Cyclic Dipeptide-Containing α-Glucosidase Inhibitor One aspect of the present invention is an α-glucosidase inhibitor containing a specific cyclic dipeptide or a salt thereof as an active ingredient.

The α-glucosidase inhibitor of the present invention includes cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)]. , Cycloisoleucil threonine [Cyclo (Ile-Thr)], cycloasparaginyl tyrosine [Cyclo (Asn-Tyr)], cycloisoleucil glycine [Cyclo (Ile-Gly)], cyclomethionyl leucine [Cyclo ( Met-Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucilleucine (Cyclo (Ile-Leu)), cyclotyrosyltyrosine (Cyclo (Tyr-Tyr)), cyclophenylalanyltyrosine (Cyclo (Phe-Tyr)), cycloglycylphenylalanine (Cyclo (Gly-Phe)), cyclo Histidylphenylalanine (Cyclo (His-Phe)), cyclo Liptophanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)] Cyclotryptophanyl threonine [Cyclo (Trp-Thr)], cycloalanyl tyrosine [Cyclo (Ala-Tyr)], cyclothreonyl tyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe -Phe)], cycloleucyltryptophan [Cyclo (Leu-Trp)], cyclotryptophanylglutamic acid [Cyclo (Trp-Glu)], cycloisoleuylphenylalanine [Cyclo (Ile-Phe)], cycloglutaminyl tyrosine (Cyclo (Gln-Tyr)), cyclotryptophanylmethionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), Cyclomethionyl phenylalanine (Cyclo (Met-Phe)), cyclovalyl leucine (Cyclo (Val-Leu)), cyclophenylalanyl tryptophan (Cyclo (Phe-Trp)), cycloglycyl histidine (Cyclo (Gly-His)) ], Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo ( Val-Val)] and cyclophenylalanylproline [Cyclo (Phe-Pro)] as an active ingredient. Preferably, three or more selected from the cyclic dipeptides or salts thereof are used as active ingredients.

From the viewpoint of the α-glucosidase inhibitory effect, the present invention provides cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)]. Val)], cycloisoleucil threonine [Cyclo (Ile-Thr)], cycloasparaginyl tyrosine [Cyclo (Asn-Tyr)], cycloisoleucil glycine [Cyclo (Ile-Gly)], cyclomethionyl leucine (Cyclo (Met-Leu)), cyclovalyltyrosine (Cyclo (Val-Tyr)), cycloisoleucil tyrosine (Cyclo (Ile-Tyr)), cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloiso Leucylleucine (Cyclo (Ile-Leu)), Cyclotyrosyltyrosine (Cyclo (Tyr-Tyr)), Cyclophenylalanyltyrosine (Cyclo (Phe-Tyr)), Cycloglycylphenylalanine (Cyclo (Gly-Phe)) ] Cyclohistidylphenylalanine [Cyclo (His-Phe )], Cyclotryptophanyltyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyltyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo ( Glu-Phe)], cyclotryptophanyl threonine [Cyclo (Trp-Thr)], cycloalanyl tyrosine [Cyclo (Ala-Tyr)], cyclothreonyl tyrosine [Cyclo (Thr-Tyr)], cyclophenylalanyl One or more selected from the group consisting of phenylalanine [Cyclo (Phe-Phe)], cycloleucyltryptophan [Cyclo (Leu-Trp)], and cyclotryptophanylglutamic acid [Cyclo (Trp-Glu)] It preferably contains a cyclic dipeptide or a salt thereof. More preferably, three or more selected from the cyclic dipeptides or salts thereof are used as active ingredients.

The content of the cyclic dipeptide or the salt thereof in the α-glucosidase inhibitor of the present invention is not particularly limited as long as the desired effect of the present invention can be obtained in consideration of its administration form, administration method and the like. It is not something. For example, when using an animal or plant-derived peptide, preferably soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide as a raw material, the content of cyclic dipeptide or a salt thereof in the present invention The total amount is 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0. × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. Further, in the α-glucosidase inhibitor of the present invention, cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)] ), Cycloisoleucil threonine [Cyclo (Ile-Thr)], cycloasparaginyl tyrosine [Cyclo (Asn-Tyr)], cycloisoleucil glycine [Cyclo (Ile-Gly)], cyclomethionyl leucine [Cyclo (Met-Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucine Leucine (Cyclo (Ile-Leu)), cyclotyrosyl tyrosine (Cyclo (Tyr-Tyr)), cyclophenylalanyl tyrosine (Cyclo (Phe-Tyr)), cycloglycylphenylalanine (Cyclo (Gly-Phe)), Cyclohistidylphenylalanine (Cyclo (His-Phe)) Cyclotryptophanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe )], Cyclotryptophanyl threonine [Cyclo (Trp-Thr)], cycloalanyl tyrosine [Cyclo (Ala-Tyr)], cyclothreonyl tyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe-Phe)], cycloleucyltryptophan [Cyclo (Leu-Trp)], cyclotryptophanyl glutamic acid [Cyclo (Trp-Glu)], cycloisoleuylphenylalanine [Cyclo (Ile-Phe)], cycloglutami Nyltyrosine [Cyclo (Gln-Tyr)], cyclotryptophanylmethionine [Cyclo (Trp-Met)], cyclovalylphenylalanine [Cyclo (Val-Phe)], cycloalanylphenylalanine [Cyclo (Al a-Phe)], cyclomethionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [ Cyclo (Gly-His)], cyclotryptophanyl arginine (Cyclo (Trp-Arg)), cyclotryptophanyl isoleucine (Cyclo (Trp-Ile)), cyclotryptophanyl tryptophan (Cyclo (Trp-Trp)), The content of cyclovalylvaline [Cyclo (Val-Val)], cyclophenylalanylproline [Cyclo (Phe-Pro)], or the salt corresponding to each is 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm And Typically, 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 ×. 10 ⁴ ppm.

Unless otherwise specified, “ppm” used herein means ppm by weight / volume (w / v), 1.0 ppm is converted to 1.0 × 10 ⁻³ mg / mL, It is converted to 1.0 × 10 ⁻⁴ wt%.

Further, when a synthetic product or a purified product is used as the cyclic dipeptide or a salt thereof, the total amount of the cyclic dipeptide or a salt thereof in the α-glucosidase inhibitor of the present invention is not particularly limited. 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm Or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm. ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. Further, when a synthetic product or purified product is used as the cyclic dipeptide or a salt thereof, cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo] contained in the α-glucosidase inhibitor of the present invention. (Asn-Val)], cycloisoleusil valine (Cyclo (Ile-Val)), cycloisoleucil threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cyclo Isoleucine glycine (Cyclo (Ile-Tly)), cyclomethionyl leucine (Cyclo (Met-Leu)), cyclovalyl tyrosine (Cyclo (Val-Tyr)), cycloisoleucil tyrosine (Cyclo (Ile-Tyr)) ], Cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucil leucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo ( Phe-Tyr)), cycloglycylphenylara Nin [Cyclo (Gly-Phe)], cyclohistidylphenylalanine [Cyclo (His-Phe)], cyclotryptophanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)] ], Cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyl tyrosine [Cyclo (Ala- Tyr)], cyclothreonyl tyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe-Phe)], cycloleucyltryptophan [Cyclo (Leu-Trp)], cyclotryptophanyl glutamic acid [ Cyclo (Trp-Glu)], cycloisoleucylphenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine (Cyclo (Gln-Tyr)), cyclotryptophanylmethionine [Cyclo (Trp-Met)], cyclovalylsulfur Nylalanine [Cyclo (Val-Phe)], cycloalanylphenylalanine [Cyclo (Ala-Phe)], cyclomethionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenyl Alanyltryptophan (Cyclo (Phe-Trp)), cycloglycyl histidine (Cyclo (Gly-His)), cyclotryptophanyl arginine (Cyclo (Trp-Arg)), cyclotryptophanyl isoleucine (Cyclo (Trp-Ile) )], Cyclotryptophanyltryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val-Val)], cyclophenylalanylproline [Cyclo (Phe-Pro)], or a salt corresponding to each The content is not particularly limited, but is, for example, 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably It is 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm.

The content of the cyclic dipeptide or a salt thereof can be measured according to a known method, and can be measured by, for example, subjecting it to LC-MS / MS.

4-2. Linear Dipeptide-Containing α-Glucosidase Inhibitor One aspect of the present invention is an α-glucosidase inhibitor containing a specific linear dipeptide or a salt thereof as an active ingredient.

Another embodiment of the present invention is an α-glucosidase inhibitor containing a linear dipeptide or a salt thereof as an active ingredient, wherein the linear dipeptide or a salt thereof is phenylalanylphenylalanine (Phe-Phe). , And / or valylmethionine (Val-Met).

The content of the linear dipeptide or the salt thereof in the α-glucosidase inhibitor of the present invention may be an amount that can achieve the desired effect of the present invention in consideration of its administration form, administration method, etc. It is not limited. For example, when a peptide derived from animals or plants, preferably soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide is used as a raw material, the linear dipeptide or salt thereof in the present invention is contained. The total amount is 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, preferably 1. 0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1 0.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. Further, the content of phenylalanylphenylalanine (Phe-Phe), valylmethionine (Val-Met), or a salt corresponding to each in the α-glucosidase inhibitor of the present invention is 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm.

When a synthetic product or purified product is used as the linear dipeptide or salt thereof, the total content of the linear dipeptide or salt thereof in the α-glucosidase inhibitor of the present invention is not particularly limited. Is, for example, 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1. It is 0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. In addition, when using a synthetic product or a purified product as a linear dipeptide or a salt thereof, phenylalanylphenylalanine (Phe-Phe), valylmethionine (Val-Met), which are included in the α-glucosidase inhibitor of the present invention, Or although content of the salt corresponding to each is not specifically limited, For example, it is 1.0x10 ppm or more, Preferably it is 1.0x10 < ² > ppm or more, More preferably, it is 1.0x10 < ³ > ppm Or more, 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2 It is 0.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm.

The content of the linear dipeptide or a salt thereof can be measured according to a known method, and can be measured by, for example, subjecting it to LC-MS / MS.

The α-glucosidase inhibitor of the present invention may contain either the cyclic dipeptide or the linear dipeptide, or may contain both the cyclic dipeptide and the linear dipeptide.

4-3. Other Components The agent of the present invention can contain any additive used in addition to the cyclic or linear dipeptide or a salt thereof, and any component used in ordinary agents, depending on the form. Examples of these additives and / or ingredients include vitamins, minerals, nutritional ingredients or fragrances, antioxidants, organic acids, organic acid salts, inorganic acids, inorganic acid salts, inorganic salts, pigments, emulsifiers , Preservatives, seasonings, sweeteners, acidulants, gums, oils, amino acids, fruit juice extracts, or vegetable extracts, as well as excipients, binders, emulsifiers, Examples include, but are not limited to, tonicity agents (isotonic agents), buffers, solubilizers, preservatives, stabilizers, antioxidants, colorants, coagulants, pH adjusters, or coating agents. It is not something.

4-4. Use The α-glucosidase inhibitor of the present invention is characterized by containing an effective amount of the above-mentioned cyclic or linear dipeptide or a salt thereof, thereby inhibiting the α-glucosidase activity, thereby gently absorbing sugar. Effect to moderate absorption of sugar contained in the diet, effect to moderate digestion and absorption of carbohydrates, effect to suppress sugar absorption, effect to suppress blood sugar increase after meals, or moderate increase in blood sugar after meals Effects can be obtained. Therefore, one embodiment of the present invention is an α-glucosidase inhibitor for suppressing absorption of dietary sugar, which contains a cyclic or linear peptide or a salt thereof as an active ingredient. In one embodiment, the present invention is an α-glucosidase inhibitor for suppressing an increase in blood glucose level, which contains a cyclic or linear dipeptide or a salt thereof as an active ingredient. Furthermore, the present invention is also an α-glucosidase inhibitor for preventing diabetes, which contains a cyclic or linear dipeptide or a salt thereof as an active ingredient. In addition, the present invention is also a lipase inhibitor for suppressing digestion and absorption of carbohydrates, which contains a cyclic or linear dipeptide or a salt thereof as an active ingredient.

The α-glucosidase inhibitor of the present invention is characterized by containing an effective amount of the aforementioned cyclic or linear dipeptide or a salt thereof, thereby inhibiting α-glucosidase and promoting or absorbing the decomposition of dietary sugar. Can be suppressed, or a decrease in blood glucose level can be promoted or increased. In addition to diabetes, subjects requiring these effects include diseases that cause hyperglycemic symptoms such as Cushing's syndrome, hyperthyroidism, pancreatitis, hepatitis, cirrhosis, etc., for prevention, improvement, or treatment of these diseases It can be suitably used.

The present invention, for example, in order to moderate sugar absorption, to gently absorb sugar contained in meals, to moderate digestive absorption of carbohydrates, to suppress sugar absorption, to increase blood sugar after meals It can be provided with explicit or implicit indication that it is used to suppress blood glucose, to moderate postprandial blood glucose rise, or to prevent diabetes.

The α-glucosidase inhibitor of the present invention is, for example, a tablet, granule, powder according to a known method by adding the above-mentioned other components to the raw material containing the cyclic or linear dipeptide or a salt thereof as required. It can be formulated into a solid agent such as a powder or capsule, or a liquid agent such as a normal solution, suspension or emulsion. These agents can be taken with water or the like as it is. Moreover, after preparing the form (for example, powder form and granule form) which can be mix | blended easily, it can use, for example as a raw material of a pharmaceutical.

The present invention can be provided in the form of an agent as an example, but is not limited to this form. The α-glucosidase inhibitor of the present invention can be provided as the composition as it is or as a composition containing the agent. Examples of such compositions include, but are not limited to, pharmaceuticals (pharmaceutical compositions), food and drink (beverages, foods, etc.), cosmetics (cosmetic compositions), and the like.

The α-glucosidase inhibitor of the present invention can be applied to any therapeutic use (medical use) or non-therapeutic use (non-medical use). Specifically, it does not belong to pharmaceuticals, quasi drugs, cosmetics, etc. or the Pharmaceutical Affairs Law, but has the effect of mildly absorbing sugar, the effect of gently absorbing sugar contained in meals, carbohydrates Explicitly or implicitly clarifies the effect of relaxing digestion and absorption of sugar, the effect of suppressing sugar absorption, the effect of suppressing postprandial blood sugar increase, the effect of moderate postprandial blood glucose increase, or the effect of preventing diabetes Use as a composition is mentioned.

The α-glucosidase inhibitor of the present invention can be taken by an appropriate method according to the form. The intake method is not particularly limited as long as the cyclic dipeptide of the present invention or a salt thereof can be transferred into the circulating blood. For example, oral solid preparations such as tablets, coated tablets, granules, powders, or capsules, oral liquid preparations such as oral liquids, syrups, injections, external preparations, suppositories, or transdermal absorption agents, etc. However, the present invention is not limited thereto. In addition, in this specification, ingestion is used as what includes all aspects of ingestion, taking, or drinking.

The dose of the α-glucosidase inhibitor of the present invention is set in a timely manner according to the form, administration method, purpose of use, and age, weight and symptoms of the patient or animal to be administered, and is not constant. The effective human intake of the cyclic or linear dipeptide of the present invention or a salt thereof in the present invention is not constant, but for example, it is preferably 10 mg or more, more preferably 100 mg or more per day for a human with a body weight of 50 kg. . Further, administration may be performed once or several times within one day within a desired dose range. The administration period is also arbitrary. Here, the effective human intake of the cyclic or linear dipeptide of the present invention or a salt thereof is the total intake of the cyclic or linear dipeptide or a salt thereof showing an effective effect in humans. Or the kind of linear dipeptide is not specifically limited.

The subject of ingestion of the α-glucosidase inhibitor of the present invention is preferably a human, but domestic animals such as cattle, horses and goats, pet animals such as dogs, cats and rabbits, or mice, rats, guinea pigs and monkeys. Or other experimental animals. When administering a non-human animal to a subject, the amount used per day for about 20 g per mouse is the content of the active ingredient in the agent, the state of the subject of application, body weight, sex, age, etc. Usually, the total amount of the cyclic or linear dipeptide or its salt is preferably 10 mg / kg or more, more preferably 100 mg / kg or more, although it varies depending on the conditions.

5). Food and drink for α-glucosidase inhibition 5-1. Cyclic dipeptide-containing α-glucosidase-inhibiting food or drink One aspect of the present invention is an α-glucosidase-inhibiting food or drink containing an amino acid-containing cyclic dipeptide or a salt thereof as an active ingredient, the cyclic dipeptide or its Salts are cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cycloisoleucil threonine [ Cyclo (Ile-Thr)], cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucine glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine (Cyclo (Met-Leu)), cyclo Valyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucine leucine [Cyclo (Ile-Leu)] ], Cyclotylo Rutyrosine (Cyclo (Tyr-Tyr)), cyclophenylalanyltyrosine (Cyclo (Phe-Tyr)), cycloglycylphenylalanine (Cyclo (Gly-Phe)), cyclohistidylphenylalanine (Cyclo (His-Phe)) Cyclotryptophanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Glu- Phe)], cyclotryptophanyl threonine (Cyclo (Trp-Thr)), cycloalanyl tyrosine (Cyclo (Ala-Tyr)), cyclothreonyl tyrosine (Cyclo (Thr-Tyr)), cyclophenylalanyl phenylalanine [ Cyclo (Phe-Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleuylphenylalanine (Cyclo (Ile-Phe)), cyclo Glutaminyltyrosine [Cyclo (Gln-Tyr)], cyclotryptophanylmethionine [Cyclo (Trp-Met)], cyclovalylphenylalanine [Cyclo (Val-Phe)], cycloalanylphenylalanine [Cyclo (Ala-Phe)] Cyclomethionylphenylalanine (Cyclo (Met-Phe)), Cyclovalylleucine (Cyclo (Val-Leu)), Cyclophenylalanyltryptophan (Cyclo (Phe-Trp)), Cycloglycylhistidine (Cyclo (Gly-His) )], Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyltryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val-Val)], and cyclophenylalanylproline [Cyclo (Phe-Pro)], or one or more selected from the group consisting of. Preferably, it contains three or more selected from the cyclic dipeptides or salts thereof.

From the viewpoint of the α-glucosidase inhibitory effect, the food and drink of the present invention are cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cycloisoleucil threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclo Methionylleucine [Cyclo (Met-Leu)], Cyclovalyltyrosine [Cyclo (Val-Tyr)], Cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], Cyclomethionylisoleucine [Cyclo (Met-Ile)] , Cycloisoleucil leucine [Cyclo (Ile-Leu)], cyclotyrosyl tyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyl tyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly -Phe)], cyclohistidylphenylalanine [Cyc lo (His-Phe)], cyclotryptophanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cyclo Glutamylphenylalanine (Cyclo (Glu-Phe)), cyclotryptophanyl threonine (Cyclo (Trp-Thr)), cycloalanyl tyrosine (Cyclo (Ala-Tyr)), cyclothreonyl tyrosine (Cyclo (Thr-Tyr)) , Cyclophenylalanylphenylalanine [Cyclo (Phe-Phe)], cycloleucyltryptophan [Cyclo (Leu-Trp)], and cyclotryptophanylglutamic acid [Cyclo (Trp-Glu)] Or it is preferable to contain 2 or more cyclic dipeptide or its salt. Moreover, it is more preferable to contain three or more selected from the cyclic dipeptide or a salt thereof.

The content of the cyclic dipeptide or the salt thereof in the food or drink of the present invention is not particularly limited as long as the desired effect of the present invention is obtained in consideration of its administration form, administration method and the like. Absent. For example, when using an animal or plant-derived peptide, preferably soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide as a raw material, the content of cyclic dipeptide or a salt thereof in the present invention The total amount is 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0. × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. In addition, cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotryptophan Nyltyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyltyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], cyclo Tryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe-Phe )], Cycloleucyltryptophan [Cyclo (Leu-Trp)], cyclotryptophanyl glutamic acid [Cyclo (Trp-Glu)], cycloisoleucil phenylalanine [Cyclo (Ile-Phe)], cycloglutaminyl tyrosine [Cyclo (Gln-Tyr)], cyclotryptophanyl methionine [Cyclo (Trp-Met)], cyclovalylphenylalanine [Cyclo (Val-Phe)], cycloalanylphenylalanine [Cyclo (Ala-Phe)], cyclomethan Onylphenylalanine (Cyclo (Met-Phe)), cyclovalylleucine (Cyclo (Val-Leu)), cyclophenylalanyltryptophan (Cyclo (Phe-Trp)), cycloglycylhistidine (Cyclo (Gly-His)) Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], cyclophenylalanylproline [Cyclo (Phe-Pro)], or the corresponding salt content is 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, Preferably it is 1.0 × 10 ³ ppm or more, 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, Is 1. ^{× 10 ~ 2.0 × 10 5 ppm} , preferably from ^{^{1.0 × 10 2 ~ 1.0 × 10}} 5 ppm, more preferably ^{^{1.0 × 10 3 ~ 2.5 × 10}} 4 ppm.

In addition, when a synthetic product or a purified product is used as the cyclic dipeptide or a salt thereof, the total content of the cyclic dipeptide or the salt thereof in the food or drink of the present invention is not particularly limited. × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, and more Preferably it is 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, and more Preferably, it is 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. In addition, when a synthetic product or a purified product is used as the cyclic dipeptide or a salt thereof, cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn- Val)], cycloisoleucine valine [Cyclo (Ile-Val)], cycloisoleucil threonine [Cyclo (Ile-Thr)], cycloasparaginyl tyrosine [Cyclo (Asn-Tyr)], cycloisoleucil Glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine (Cyclo (Met-Leu)), cyclovalyl tyrosine (Cyclo (Val-Tyr)), cycloisoleuyl tyrosine (Cyclo (Ile-Tyr)), cyclo Methionyl isoleucine (Cyclo (Met-Ile)), cycloisoleucil leucine (Cyclo (Ile-Leu)), cyclotyrosyl tyrosine (Cyclo (Tyr-Tyr)), cyclophenylalanyl tyrosine (Cyclo (Phe-Tyr) )], Cycloglycylphenylalanine [Cyclo (Gly-Phe)] , Cyclohistidylphenylalanine [Cyclo (His-Phe)], cyclotryptophanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo ( Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [ Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine (Cyclo (Phe-Phe)), cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanylglutamic acid (Cyclo (Trp-Glu)), cyclo Isoleucylphenylalanine (Cyclo (Ile-Phe)), cycloglutaminyltyrosine (Cyclo (Gln-Tyr)), cyclotryptophanylmethionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyc lo (Val-Phe)], cycloalanylphenylalanine [Cyclo (Ala-Phe)], cyclomethionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyl Tryptophan (Cyclo (Phe-Trp)), cycloglycyl histidine (Cyclo (Gly-His)), cyclotryptophanyl arginine (Cyclo (Trp-Arg)), cyclotryptophanyl isoleucine (Cyclo (Trp-Ile)) , Cyclotryptophanyltryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val-Val)], cyclophenylalanylproline [Cyclo (Phe-Pro)], or the corresponding salt content Is not particularly limited, for example, 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, good Properly is 1.0 × ¹⁰ 5 ppm or less, more preferably 2.5 × ¹⁰ 4 ppm or less, ^{typically, 1.0 × 10 ~ 2.0 × 10} 5 ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm.

5-2. Linear Dipeptide-Containing α-Glucosidase Inhibiting Food / Beverage One aspect of the present invention is an α-glucosidase-inhibiting food / beverage containing, as an active ingredient, a linear dipeptide containing amino acid as a structural unit or a salt thereof. A linear dipeptide or a salt thereof contains phenylalanylphenylalanine (Phe-Phe) and / or valylmethionine (Val-Met).

The content of the linear dipeptide or its salt in the food or drink of the present invention is not particularly limited as long as the desired effect of the present invention can be obtained in consideration of its administration form, administration method and the like. It is not a thing. For example, when a peptide derived from animals or plants, preferably soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide is used as a raw material, the linear dipeptide or salt thereof in the present invention is contained. The total amount is 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, preferably 1. 0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1 0.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. In addition, the content of phenylalanylphenylalanine (Phe-Phe), valylmethionine (Val-Met), or a salt corresponding to each in the food and drink of the present invention is 1.0 × 10 ppm or more, preferably 1.0. × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm Typically, 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm.

In addition, when using a synthetic product or a purified product as a linear dipeptide or a salt thereof, the total content of the linear dipeptide or a salt thereof in the food or drink of the present invention is not particularly limited, for example, 1.0 × 10 5 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more, and 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 × 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm. In addition, when using a synthetic product or purified product as a linear dipeptide or a salt thereof, phenylalanylphenylalanine (Phe-Phe), valylmethionine (Val-Met), or each included in the food or drink of the present invention, The content of the corresponding salt is not particularly limited, and is, for example, 1.0 × 10 ppm or more, preferably 1.0 × 10 ² ppm or more, more preferably 1.0 × 10 ³ ppm or more. 2.0 × 10 ⁵ ppm or less, preferably 1.0 × 10 ⁵ ppm or less, more preferably 2.5 × 10 ⁴ ppm or less, typically 1.0 × 10 to 2.0 ×. It is 10 ⁵ ppm, preferably 1.0 × 10 ² to 1.0 × 10 ⁵ ppm, more preferably 1.0 × 10 ³ to 2.5 × 10 ⁴ ppm.

Moreover, the food and drink of the present invention may contain either the cyclic dipeptide or the linear dipeptide, or may contain both the cyclic dipeptide and the linear dipeptide.

5-3. Other components The food and drink of the present invention, as long as the effect is not impaired, according to the form, in addition to the cyclic or linear dipeptide or a salt thereof, any additive, any component used for ordinary agents Can be contained. Examples of these additives and / or ingredients include vitamins, minerals, nutritional ingredients, fragrances, antioxidants, organic acids, organic acid salts, inorganic acids, inorganic acid salts, inorganic salts, pigments, etc. In addition to physiologically active ingredients such as emulsifiers, preservatives, seasonings, sweeteners, acidulants, gums, oils, amino acids, fruit juices, or vegetable extracts, excipients, binders, emulsifiers incorporated in the formulation. , Tensioning agents (isotonic agents), buffers, solubilizers, preservatives, stabilizers, antioxidants, colorants, coagulants, pH adjusters or coating agents, but are not limited thereto. Is not to be done.

The food or drink of the present invention is not particularly limited, and is, for example, a beverage or food containing the cyclic or linear dipeptide or a salt thereof. The content of the cyclic or linear dipeptide or a salt thereof in the beverage or food is as described above.

For example, when preparing a known food or drink, the food or drink of the present invention is prepared according to a known method for producing a food or drink by mixing a predetermined amount of the cyclic or linear dipeptide or a salt thereof with the raw material. Alternatively, it may be prepared by adding the cyclic or linear dipeptide or a salt thereof to an already-known known food or drink so as to have the predetermined amount, and dissolving and / or suspending. The known food or drink may originally contain the cyclic or linear dipeptide or a salt thereof, and if the cyclic or linear dipeptide of the present invention is a predetermined amount, it is appropriately blended. It can also be prepared.

5-4. Use The food and drink of the present invention can obtain the effect of inhibiting α-glucosidase activity by containing the cyclic or linear dipeptide or a salt thereof. Thereby, in order to moderate the absorption of sugar in order to moderate the absorption of sugar in the food and drink of the present invention, in order to moderate the digestion and absorption of carbohydrates, to suppress the absorption of sugar, It can be used to suppress an increase in blood glucose after meals, to moderate an increase in blood glucose after meals, or to prevent diabetes. Examples of the subject requiring the effect include diseases that cause hyperglycemic symptoms such as Cushing's syndrome, hyperthyroidism, pancreatitis, hepatitis, or cirrhosis in addition to diabetes, and are suitable for prevention, improvement, or treatment of the disease Can be used.

The food and drink of the present invention is, for example, to moderate sugar absorption, to gently absorb sugar contained in meals, to gently digest carbohydrate absorption, to suppress sugar absorption, It can be provided with explicit or implicit indication that it is used to suppress the increase in blood glucose, to moderate the increase in blood glucose after meals, or to prevent diabetes.

The food and drink of the present invention is not particularly limited, and examples thereof include beverages and foods.

Specific examples of the beverage of the present invention include oolong tea beverage, black tea beverage, green tea beverage, fruit juice beverage, vegetable juice, sports drink, isotonic beverage, enhanced water, mineral water, near water, nutritional drink, beauty drink, or various Examples include alcoholic beverages. In addition, the beverage may contain an antioxidant, a fragrance, an organic acid, an organic acid salt, an inorganic acid, an inorganic acid salt, an inorganic salt, a pigment, an emulsifier, a preservative, a seasoning, a sweetener, and an acidity as necessary. Additives such as ingredients, gums, oils, vitamins, amino acids, fruit juice extracts, vegetable extracts, pH adjusters, or quality stabilizers may be used alone or in combination.

Further, the beverage of the present invention is made into a container-packed beverage through a process such as sterilization as necessary. For example, a sterilized container-packed beverage can be produced by a method of performing heat sterilization after filling a beverage into a container, or a method of sterilizing a beverage and then filling the container in an aseptic environment.

The type of container used for the container-packed beverage is not particularly limited. For example, a plastic container such as a plastic bottle, a paper container such as a paper pack, a glass container such as a glass bottle, a metal container such as an aluminum can or a steel can, an aluminum pouch Any container that is usually used for beverages can be used.

One embodiment of the present invention is a food containing the cyclic or linear dipeptide or a salt thereof, and includes, for example, health foods, functional foods (special health foods, conditional health foods, nutritional functional foods, etc. Special-purpose foods and health supplements. The content of the cyclic or linear dipeptide or a salt thereof in the food of the present invention is as described above.

The food of the present invention may be prepared according to a known food production method, for example, when preparing a known food, mixing a predetermined amount of the cyclic or linear dipeptide or a salt thereof with the raw material, Moreover, you may prepare by adding the said cyclic | annular or linear dipeptide or its salt to the well-known well-known food so that it may become the said predetermined amount. In addition, the known food may originally contain the cyclic or linear dipeptide or a salt thereof, and if the cyclic or linear dipeptide of the present invention is a predetermined amount, it is appropriately blended. Can be prepared.

The food and drink of the present invention can be ingested by an appropriate method according to the form. The intake method is not particularly limited as long as the cyclic or linear dipeptide of the present invention or a salt thereof can be transferred into the circulating blood. In addition, in this specification, ingestion includes all aspects of ingestion, taking, or drinking.

The intake of the food and drink according to the present invention is appropriately set according to the form, administration method, purpose of use, and age, weight, and symptom of the patient or animal to be ingested by the composition, and is not constant. For example, the effective human intake of the cyclic or linear dipeptide of the present invention or a salt thereof of the present invention is not constant, but is preferably 10 mg or more, more preferably 100 mg or more per day for a human body weight of 50 kg, for example. It is. Further, administration may be performed once or several times within one day within a desired dose range. The administration period is also arbitrary. Here, the effective human intake of the cyclic or linear dipeptide of the present invention or a salt thereof is the total intake of the cyclic or linear dipeptide or a salt thereof showing an effective effect in humans, The kind of cyclic or linear dipeptide is not particularly limited.

In the present specification, the subject of intake of the food and drink of the present invention is preferably a human, but a domestic animal such as a cow, horse, goat, a pet animal such as a dog, a cat, a rabbit, or a mouse, rat, guinea pig. Or a laboratory animal such as a monkey. When a non-human animal is administered to a subject, the amount used per day for about 20 g per mouse is the content of the active ingredient in the composition, the state of the subject, weight, sex, age, etc. Usually, the total amount of the cyclic or linear dipeptide or its salt is preferably 10 mg / kg or more, more preferably 100 mg / kg or more.

The food or drink of the present invention exhibits various health functions (or physiological effects) due to cyclic or linear dipeptides or salts thereof which are health function ingredients (participating ingredients, active ingredients). Here, the health functional component refers to a component that is useful for maintaining and promoting health by ingesting a certain amount. Therefore, the food / beverage products of this invention can be used for the use resulting from such a health functional ingredient. Specifically, it has the effect of mildly absorbing sugar, the effect of relaxing the absorption of sugar in the diet, the effect of relaxing the digestion and absorption of carbohydrates, the effect of suppressing the absorption of sugar, and the increase in blood sugar after eating Examples thereof include use as a food and drink that explicitly or implicitly appeals for an effect of suppressing, an effect of mildly increasing blood sugar after meals, or an effect of preventing diabetes.

In another aspect, the present invention relates to a food or drink containing a cyclic or linear dipeptide or a salt thereof, which is labeled with a function exhibited by α-glucosidase inhibition. Such display or function display is not particularly limited. For example, “smooth absorption of sugar”, “moderate absorption of sugar contained in meal”, “moderate digestion absorption of carbohydrate” , “Suppress sugar absorption”, “suppress postprandial blood glucose increase”, “moderate postprandial blood glucose increase”, or “prevent diabetes”. In the present specification, the display such as the display and the function display may be attached to the food or drink itself, or may be attached to a container or packaging of the food or drink.

6). Use of cyclic or linear dipeptide or a salt thereof for inhibiting α-glucosidase One embodiment of the present invention is the use of a specific cyclic dipeptide or a salt thereof having amino acid as a constituent unit for α-glucosidase inhibition. . Preferably, cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cycloisoleucil threonine [ Cyclo (Ile-Thr)], cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucine glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine (Cyclo (Met-Leu)), cyclo Valyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucine leucine [Cyclo (Ile-Leu)] ], Cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohistidylphenylalanine [Cyclo ( His-Phe)), cyclotryptophanyltyrosine [C yclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], cyclotrypto Fanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe-Phe)] Cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine (Cyclo (Gln) -Tyr)], cyclotryptophanylmethionine [Cyclo (Trp-Met)], cyclovalylphenylalanine [Cyclo (Val-Phe)], cycloalanylphenylalanine [Cyclo (Ala-Phe)], cyclomethionylphenyl Lanin (Cyclo (Met-Phe)), cyclovalyl leucine (Cyclo (Val-Leu)), cyclophenylalanyl tryptophan (Cyclo (Phe-Trp)), cycloglycyl histidine (Cyclo (Gly-His)), cyclo Tryptophanyl arginine (Cyclo (Trp-Arg)), cyclotryptophanyl isoleucine (Cyclo (Trp-Ile)), cyclotryptophanyl tryptophan (Cyclo (Trp-Trp)), cyclovalylvaline (Cyclo (Val-Val-Val)) )], And one or more cyclic dipeptides selected from the group consisting of cyclophenylalanylproline [Cyclo (Phe-Pro)] or salts thereof for use in α-glucosidase inhibition. More preferably, it is a use for inhibiting α-glucosidase containing at least three selected from the above cyclic dipeptides or salts thereof.

Another embodiment of the present invention is the use of a specific linear dipeptide having an amino acid as a structural unit or a salt thereof for α-glucosidase inhibition. Preference is given to the use of phenylalanylphenylalanine (Phe-Phe), valylmethionine (Val-Met) or their corresponding salts for α-glucosidase inhibition.

Further, one embodiment of the present invention is also the use of α-glucosidase inhibition of those containing both the cyclic dipeptide and the linear dipeptide.

Examples include, but are not limited to, use for preventing or treating hyperglycemia symptoms such as diabetes, Cushing's syndrome, hyperthyroidism, pancreatitis, hepatitis, cirrhosis and the like. The use is in a human or non-human animal and may be a therapeutic or non-therapeutic use. Here, “non-therapeutic” is a concept that does not include a medical act, that is, a treatment act on the human body by treatment.

7). Method for Inhibiting α-Glucosidase One aspect of the present invention comprises administering α-glucosidase to a subject in need of α-glucosidase inhibition, comprising administering a therapeutically effective amount of a specific cyclic dipeptide or a salt thereof as an active ingredient. A method of inhibiting is provided. Preferably, cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cycloisoleucil threonine [ Cyclo (Ile-Thr)], cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucine glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine (Cyclo (Met-Leu)), cyclo Valyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucine leucine [Cyclo (Ile-Leu)] ], Cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohistidylphenylalanine [Cyclo ( His-Phe)), cyclotryptophanyltyrosine [C yclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], cyclotrypto Fanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe-Phe)] Cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine (Cyclo (Gln) -Tyr)], cyclotryptophanylmethionine [Cyclo (Trp-Met)], cyclovalylphenylalanine [Cyclo (Val-Phe)], cycloalanylphenylalanine [Cyclo (Ala-Phe)], cyclomethionylphenyl Lanin (Cyclo (Met-Phe)), cyclovalyl leucine (Cyclo (Val-Leu)), cyclophenylalanyl tryptophan (Cyclo (Phe-Trp)), cycloglycyl histidine (Cyclo (Gly-His)), cyclo Tryptophanyl arginine (Cyclo (Trp-Arg)), cyclotryptophanyl isoleucine (Cyclo (Trp-Ile)), cyclotryptophanyl tryptophan (Cyclo (Trp-Trp)), cyclovalylvaline (Cyclo (Val-Val-Val)) )], And cyclophenylalanylproline [Cyclo (Phe-Pro)], comprising administering one or more cyclic dipeptides or salts thereof selected from the group consisting of a therapeutically effective amount as an active ingredient, Methods of inhibiting α-glucosidase are provided. More preferably, the present invention provides a method for inhibiting α-glucosidase, comprising administering a therapeutically effective amount using as an active ingredient a substance containing three or more selected from the above cyclic dipeptides or salts thereof.

Another embodiment of the present invention is a method for inhibiting α-glucosidase, comprising administering to a subject in need of α-glucosidase inhibition a therapeutically effective amount of a specific linear dipeptide or a salt thereof as an active ingredient. Is to provide. Preferably, a method for inhibiting α-glucosidase, comprising administering a therapeutically effective amount of phenylalanylphenylalanine (Phe-Phe), valylmethionine (Val-Met), or a salt corresponding to each as an active ingredient is provided. To do.

Also, one embodiment of the present invention provides a method for inhibiting α-glucosidase, comprising administering a therapeutically effective amount using as an active ingredient a substance containing both the cyclic dipeptide and the linear dipeptide.

The subject requiring α-glucosidase inhibition is the same as the subject to which the α-glucosidase inhibitor of the present invention is administered.

In the present specification, the therapeutically effective amount means that when the cyclic or linear dipeptide of the present invention or a salt thereof is administered to the subject, the α-glucosidase activity is inhibited as compared with a subject not administered. It is the amount to be done. The specific effective amount is appropriately set according to the administration form, administration method, purpose of use, age, weight, symptoms, etc. of the individual and is not constant.

In the method of the present invention, the specific cyclic or linear dipeptide or a salt thereof is administered as it is or as a composition containing the specific cyclic or linear dipeptide or a salt thereof so that the therapeutically effective amount is obtained. May be.

According to the method of the present invention, α-glucosidase can be inhibited without causing side effects.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this does not limit the scope of the present invention. Those skilled in the art can use the method of the present invention with various changes and modifications, and these are also included in the scope of the present invention.
Example 1: Inhibitory effect of α-glucosidase by cyclic dipeptide
1. The reagent cyclic dipeptide used was synthesized by Kobe Natural Products Chemical Co., Ltd. The α-glucosidase was obtained from Toyobo Co., Ltd., the α-glucosidase assay kit was obtained from BIOASSAY SYSTEM, and the 96-well clear plate was obtained from Greiner.

Using the assay buffer attached to the α-glucosidase assay kit, a 2 mM 4-nitrophenyl-α-glucopyranoside (α-NPG) Substrate solution was prepared and used as a substrate solution. In addition, an assay buffer was added to α-glucosidase to make 50 U / L to obtain an enzyme solution.
2. α-Glucosidase Inhibitory Effect in Vitro α-Glucosidase inhibitory effect in vitro was examined for 210 kinds of cyclic dipeptides. Specifically, 10 μL of each cyclic dipeptide dissolved in DMSO was added to each well of a 96-well plate (the final concentration of each cyclic dipeptide was 500 μM), and then 50 μL of the substrate solution was added (the final concentration of the substrate was 1 mM). Add 40 μL of enzyme solution to the cyclic dipeptide-substrate mixture (the final concentration of α-glucosidase is 20 U / L), and after 10 minutes, use a spectrophotometer (Synegy HT, manufactured by Bio Tek) for absorbance at 405 nm Was measured. The α-glucosidase inhibition rate (%) was calculated by the following formula. Table 1 shows the inhibition rate of cyclic dipeptides for which an inhibition rate of 20% or more was confirmed. Table 2 shows the α-glucosidase inhibitory activities (IC50 values) of 25 types of cyclic dipeptides.

A: Absorbance at 405 nm of α-glucosidase added and no sample added group B: Absorbance at 405 nm of α-glucosidase added and unadded sample group C: Absorbance at 405 nm of α-glucosidase added and sample added group D: α-glucosidase Absorbance at 405 nm of the non-added and sample-added groups

Example 2: Comparison of α-glucosidase inhibitory effect of cyclic dipeptide and linear dipeptide The α-glucosidase inhibitory effect of cyclic dipeptide and linear dipeptide was compared. The test was performed according to Example 1. FIG. 1 shows the results of Cyclo (Thr-Tyr), Cyclo (Phe-Phe), and Phe-Phe, and FIG. 2 shows the results of Cyclo (Met-Val), Met-Val, and Val-Met.

As a result of the experiment, as shown in FIGS. 1 and 2, all cyclic dipeptides showed an α-glucosidase inhibition rate of 60% or more. The α-glucosidase inhibitory effect of this cyclic dipeptide was significantly higher than that of the linear dipeptide (p <0.05, Dunnett's test).

Further, although not as much as the cyclic dipeptide, among the linear peptides, phenylalanylphenylalanine (Phe-Phe) and valylmethionine (Val-Met) showed an α-glucosidase inhibitory effect of 10% or more.

The present invention provides an α-glucosidase inhibitor and a food or drink containing a specific cyclic or linear dipeptide or a salt thereof as an active ingredient. Therefore, the present invention can provide an effective and new means that contributes to suppression of an increase in blood glucose level after meals, prevention or improvement of diabetes, and the like, and thus has high industrial applicability.

Claims

An α-glucosidase inhibitor containing, as an active ingredient, a cyclic dipeptide having an amino acid as a structural unit or a salt thereof,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and one or more selected from the group consisting of cyclophenylalanylproline [Cyclo (Phe-Pro)], the α-glucosidase inhibitor.
Cyclic dipeptides or salts thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cycloiso Leucylthreonine (Cyclo (Ile-Thr)), cycloasparaginyltyrosine (Cyclo (Asn-Tyr)), cycloisoleucineglycine (Cyclo (Ile-Gly)), cyclomethionylleucine (Cyclo (Met-Leu) )], Cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucine leucine [Cyclo ( Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohistidyl Phenylalanine [Cyclo (His-Phe)], cyclotrypto Anthyrosine (Cyclo (Trp-Tyr)), cyclotryptophanylalanine (Cyclo (Trp-Ala)), cyclomethionyl tyrosine (Cyclo (Met-Tyr)), cycloglutamylphenylalanine (Cyclo (Glu-Phe)), cyclo Tryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe-Phe )], Cycloleucyltryptophan [Cyclo (Leu-Trp)], and cyclotryptophanyl glutamic acid [Cyclo (Trp-Glu)], one or more selected from the group consisting of An α-glucosidase inhibitor described in 1.
The α-glucosidase inhibitor according to claim 1, wherein the cyclic dipeptide or a salt thereof comprises three or more selected from the group according to claim 1.
The α-glucosidase inhibitor according to claim 2, wherein the cyclic dipeptide or a salt thereof comprises three or more selected from the group according to claim 2.
The α-glucosidase inhibitor according to any one of claims 1 to 4, which is used for suppressing absorption of meal-derived sugar.
The α-glucosidase inhibitor according to any one of claims 1 to 4, which is used for suppressing an increase in blood glucose level.
The α-glucosidase inhibitor according to any one of claims 1 to 4, which is used for diabetes prevention.
The α-glucosidase inhibitor according to any one of claims 1 to 4, which is used for suppressing digestion and absorption of carbohydrates.
The α-glucosidase inhibitor according to any one of claims 1 to 8, wherein the cyclic dipeptide having an amino acid as a structural unit or a salt thereof is obtained from an animal or plant derived peptide.
The α-glucosidase inhibitor according to claim 9, wherein the animal or plant-derived peptide is soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide.
A food and drink for α-glucosidase inhibition containing a cyclic dipeptide having an amino acid as a structural unit or a salt thereof as an active ingredient,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and one or more selected from the group consisting of cyclophenylalanylproline [Cyclo (Phe-Pro)].
Cyclic dipeptides or salts thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cycloiso Leucylthreonine (Cyclo (Ile-Thr)), cycloasparaginyltyrosine (Cyclo (Asn-Tyr)), cycloisoleucineglycine (Cyclo (Ile-Gly)), cyclomethionylleucine (Cyclo (Met-Leu) )], Cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleucine leucine [Cyclo ( Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohistidyl Phenylalanine [Cyclo (His-Phe)], cyclotrypto Anthyrosine (Cyclo (Trp-Tyr)), cyclotryptophanylalanine (Cyclo (Trp-Ala)), cyclomethionyl tyrosine (Cyclo (Met-Tyr)), cycloglutamylphenylalanine (Cyclo (Glu-Phe)), cyclo Tryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe-Phe )], Cycloleucyltryptophan [Cyclo (Leu-Trp)], and cyclotryptophanyl glutamic acid [Cyclo (Trp-Glu)], one or more selected from the group consisting of Food and drink as described in.
The food or drink according to claim 11, wherein the cyclic dipeptide or a salt thereof includes three or more selected from the group according to claim 11.
The food or drink according to claim 12, wherein the cyclic dipeptide or a salt thereof comprises three or more selected from the group according to claim 12.
The total amount of the cyclic dipeptide or its salt is 1.0 × 10 to 2.0 × 10 5 ppm, and the content of each of the cyclic dipeptide or its salt is 1.0 × 10 to 2.0 × 10 5 ppm The food or drink according to any one of claims 11 to 14, wherein
The food or drink according to any one of claims 11 to 15, wherein the cyclic dipeptide having an amino acid as a structural unit or a salt thereof is obtained from an animal or plant-derived peptide.
The food or drink according to claim 16, wherein the animal or plant-derived peptide is soybean peptide, tea peptide, malt peptide, rice peptide, chicken peptide, milk peptide, placenta peptide, or collagen peptide.
The food or drink according to any one of claims 11 to 17, which is labeled with a function exhibited by α-glucosidase inhibition.
The function display is selected from the group consisting of “smooth sugar absorption”, “smooth digestion and absorption of carbohydrates”, “suppresses postprandial blood sugar rise”, and “prevents diabetes” The food / beverage products of Claim 18 which are.
Use of a cyclic dipeptide having an amino acid as a structural unit or a salt thereof for inhibiting α-glucosidase,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and cyclophenylalanylproline [Cyclo (Phe-Pro)], wherein the use is one or more.
A method for inhibiting α-glucosidase, comprising using as an active ingredient a cyclic dipeptide having amino acid as a structural unit or a salt thereof,
The cyclic dipeptide or a salt thereof may be cyclomethionyl valine [Cyclo (Met-Val)], cycloasparaginyl valine [Cyclo (Asn-Val)], cycloisoleusil valine [Cyclo (Ile-Val)], cyclo Isoleucine threonine (Cyclo (Ile-Thr)), cycloasparaginyl tyrosine (Cyclo (Asn-Tyr)), cycloisoleucil glycine (Cyclo (Ile-Gly)), cyclomethionyl leucine [Cyclo (Met- Leu)], cyclovalyltyrosine [Cyclo (Val-Tyr)], cycloisoleucine tyrosine [Cyclo (Ile-Tyr)], cyclomethionylisoleucine [Cyclo (Met-Ile)], cycloisoleuylleucine [Cyclo (Ile-Leu)], cyclotyrosyltyrosine [Cyclo (Tyr-Tyr)], cyclophenylalanyltyrosine [Cyclo (Phe-Tyr)], cycloglycylphenylalanine [Cyclo (Gly-Phe)], cyclohisti Dilphenylalanine (Cyclo (His-Phe)), cyclotrip Fanyl tyrosine [Cyclo (Trp-Tyr)], cyclotryptophanylalanine [Cyclo (Trp-Ala)], cyclomethionyl tyrosine [Cyclo (Met-Tyr)], cycloglutamylphenylalanine [Cyclo (Glu-Phe)], Cyclotryptophanylthreonine [Cyclo (Trp-Thr)], cycloalanyltyrosine [Cyclo (Ala-Tyr)], cyclothreonyltyrosine [Cyclo (Thr-Tyr)], cyclophenylalanylphenylalanine [Cyclo (Phe- Phe)], cycloleucyltryptophan (Cyclo (Leu-Trp)), cyclotryptophanyl glutamic acid (Cyclo (Trp-Glu)), cycloisoleucil phenylalanine (Cyclo (Ile-Phe)), cycloglutaminyl tyrosine [ Cyclo (Gln-Tyr)], cyclotryptophanyl methionine (Cyclo (Trp-Met)), cyclovalylphenylalanine (Cyclo (Val-Phe)), cycloalanylphenylalanine (Cyclo (Ala-Phe)), cycl Methionylphenylalanine [Cyclo (Met-Phe)], cyclovalylleucine [Cyclo (Val-Leu)], cyclophenylalanyltryptophan [Cyclo (Phe-Trp)], cycloglycylhistidine [Cyclo (Gly-His)] Cyclotryptophanyl arginine [Cyclo (Trp-Arg)], cyclotryptophanyl isoleucine [Cyclo (Trp-Ile)], cyclotryptophanyl tryptophan [Cyclo (Trp-Trp)], cyclovalylvaline [Cyclo (Val -Val)], and one or more selected from the group consisting of cyclophenylalanylproline [Cyclo (Phe-Pro)].