Composition for promoting GLP-1 secretion

Abstract

The present invention addresses the problem of providing a composition capable of effectively promoting GLP-1 secretion. This problem can be solved by providing a composition for promoting GLP-1 secretion that comprises, as active ingredients, glycosylnaringenin as component (A) together with at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, methyl N-methylanthranilate, thymol and nootkatone, as component (B).

Description

Composition for promoting GLP-1 secretion

[0001] The present invention relates to a composition for promoting GLP-1 secretion, and more particularly to a composition for promoting GLP-1 secretion, comprising, as active ingredients, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone.

[0002] Endocrine cells are scattered throughout the intestinal epithelium, and it is known that gastrointestinal hormones secreted from these endocrine cells regulate the functions of other organs. Some of the gastrointestinal hormones secreted by endocrine cells are called incretins, and are secreted into the blood upon meal intake. They act on the beta cells of the islets of Langerhans in the pancreas (hereinafter referred to as "pancreatic beta cells") to promote insulin secretion.

[0003] There are two types of incretins: glucose-dependent insulinotropic polypeptide (hereinafter referred to as "GIP") and glucagon-like peptide-1 (hereinafter referred to as "GLP-1"). GIP is secreted from K cells present in the upper small intestine, and GLP-1 is secreted from L cells present in the lower small intestine.

[0004] GLP-1 is secreted into the bloodstream following meal intake and acts on pancreatic β cells to promote insulin secretion and lower blood glucose levels. GLP-1 has also been shown to inhibit glucagon secretion from pancreatic α cells, suppress appetite and food intake in the central nervous system, and delay gastric emptying (Non-Patent Document 1). Furthermore, because GLP-1 receptors are expressed in many organs and tissues in the body, including the kidneys, in addition to pancreatic β cells, GLP-1 is thought to have a variety of physiological effects in addition to those described above. For example, the antihypertensive effect of GLP-1 has been demonstrated in studies using humans and rats, and it has been found that GLP-1 receptor agonists promote urinary sodium excretion and suppress angiotensin II-induced blood pressure increases (Non-Patent Document 2). GLP-1 is also thought to contribute to the prevention of arteriosclerosis, the maintenance of bone strength, and the regulation of peripheral circadian rhythms (Non-Patent Documents 3, 4, and 5). Therefore, promoting the secretion of GLP-1 is thought to lead not only to the maintenance of homeostasis of glucose metabolism and glucose tolerance and the improvement of obesity, but also to various homeostasis in the body and the prevention and improvement of lifestyle-related diseases.

[0005] However, GLP-1 is a polypeptide, and when orally ingested, it is easily digested and decomposed in the digestive tract, resulting in a low transfer rate into the blood and a very low in vivo availability. Furthermore, even when administered subcutaneously or intravenously, GLP-1 is known to be rapidly decomposed by a degrading enzyme (dipeptidyl peptidase 4). Therefore, in order to increase the GLP-1 concentration in the body for a long period of time, it is desirable to continuously promote the secretion of endogenous GLP-1 using a method that places less strain on the body than administering GLP-1 itself exogenously.

[0006] There have been several reports on the GLP-1 secretion-promoting action of plant extracts and their components (Patent Documents 1 and 2). For example, Patent Document 1 describes honeysuckle or alkanet or processed products thereof, and Patent Document 2 describes bitter melon-derived components as having a GLP-1 secretion-promoting action. In addition, the GLP-1 secretion-promoting action of geraniol and citronellal has also been reported (Non-Patent Document 6).

[0007] As described above, although active ingredients aimed at promoting GLP-1 secretion have been proposed, the active ingredients having the effect of promoting GLP-1 secretion have poor water solubility and have not been widely usable in the food industry, etc. Furthermore, when using conventional active ingredients with water solubility issues, the GLP-1 secretion promoting effect obtained is not necessarily sufficient. Under these circumstances, there has been a demand for a GLP-1 secretion promoter that is more effective and can be incorporated into various products.

[0008] Japanese Patent Application Laid-Open No. 2016-138070 International Publication No. 2017 / 159725 Pamphlet

[0009] Monthly Diabetes Special Edition "Incretin" 2009 / 12Biochemical and Biophysical Research Communications 380, 44-49 (2009)PLoS ONE 8 (8), e70933 (2013)Journal of Endocrinology 219, 59-68 (2013)PLoS ONE 8 (11), e81119 (2013)Scientific Reports 7 (1), 1-11 (2017)

[0010] In view of the above-mentioned current situation, an object of the present invention is to provide a composition having a more effective GLP-1 secretion-promoting effect.

[0011] As a result of extensive research to solve the above-mentioned problems, the present inventors have found that a composition containing, as active ingredients, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone promotes GLP-1 secretion, and further that a composition containing glycosylnaringenin and thymol and / or nootkatone in a specific ratio has a particularly effective GLP-1 secretion-promoting effect.

[0012] That is, the present invention solves the above-mentioned problems by providing the following: (1) A composition for promoting GLP-1 secretion, comprising component (A) glycosylnaringenin and component (B) at least one active ingredient selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone. (2) The composition for promoting GLP-1 secretion according to (1) above, wherein component (A) is 3"-α-monoglucosylnaringin. (3) The composition for promoting GLP-1 secretion according to (1) or (2) above, wherein component (B) is thymol and / or nootkatone. (4) The composition for promoting GLP-1 secretion according to any one of (1) to (3) above, which contains component (A) and component (B) in a molar ratio of 10,000:1 to 1:10. (5) The composition for promoting GLP-1 secretion according to any one of (1) to (4) above, which contains component (A) in an amount of 0.0001% by mass or more. (6) The composition for promoting GLP-1 secretion according to any one of (1) to (5) above, which is used for at least one effect selected from the prevention or amelioration of obesity, diabetes, and postprandial hyperglycemia, suppression of blood glucose elevation, suppression of glucagon secretion, suppression of gastric emptying and gastric acid secretion, appetite suppression, food intake suppression, and satiety induction. (7) A composition comprising, together with component (A) glycosylnaringenin, component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone. (8) The composition according to (7) above, wherein the molar ratio of component (A) to component (B) is 10,000:1 to 1:10. (9) The composition according to (7) or (8) above, wherein component (A) is 3"-α-monoglucosylnaringin. (10) The composition for promoting GLP-1 secretion according to any one of (7) to (9) above, wherein the component (B) is thymol and / or nootkatone. (11) The composition according to any one of (7) to (10) above, which contains 0.0001% by mass or more of the component (A). (12) A food or drink comprising the composition according to any one of (1) to (11) above.(13) A supplement comprising the composition according to any one of (1) to (11) above. (14) A flavoring comprising the composition according to any one of (1) to (11) above. (15) A pharmaceutical or quasi-drug comprising the composition according to any one of (1) to (11) above. (16) A feed comprising the composition according to any one of (1) to (11) above. (17) The food or drink according to (12) above, which is in the form of a liquid, fluid, gel, semi-solid, solid, or powder. (18) The supplement according to (13) above, which is in the form of a liquid, gel, paste, tablet, pill, capsule, powder, granule, fine granule, or lozenge. (19) The flavoring according to (14) above, which is in the form of a water-soluble flavoring, an oil-soluble flavoring, an emulsified flavoring, or a powdered flavoring. (20) The pharmaceutical or quasi-drug according to (15) above, which is in the form of a liquid, fluid, gel, semi-solid, solid, tablet, pill, capsule, powder, granule, fine granule, or lozenge. (21) The feed according to (16) above, which is in the form of a liquid, powder, pellet, flake, or mash.

[0013] The composition for promoting GLP-1 secretion of the present invention exhibits an effective GLP-1 secretion promoting effect.

[0014] The present invention relates to a composition for promoting GLP-1 secretion, which comprises, as active ingredients, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone. Hereinafter, components (A) and (B), which are the active ingredients of the composition of the present invention, will be described in order.

[0015] As used herein, "glycosylnaringenin" is a type of flavanone and is a general term for glycosides with "naringenin" as the aglycone, which has the structure shown in Chemical Formula 1 below.

[0016] Chemical formula 1:

[0017] Representative compounds encompassed by the term "glycosylnaringenin" as used herein include "naringin" (chemical formula 2 below), which has a structure in which neohesperidose (α-rhamnosyl(1→2)glucose) is beta-bonded to the 7-OH group of naringenin, and "3"-α-monoglucosylnaringin" (chemical formula 3 below), which has a structure in which glucose is α-bonded to the 3-OH group (3" position) of the glucose residue in the neohesperidose of naringin. Naringin is a substance contained, for example, in the unripe peel of citrus fruits, and has antioxidant properties. It has been found to have physiological effects such as strengthening capillaries, preventing bleeding, regulating blood pressure, and lowering cholesterol, as well as TNF-inducing activity, which maintains homeostasis in the body.

[0018] Chemical formula 2:

[0019] Chemical formula 3:

[0020] Furthermore, the term "glycosylnaringenin" as used herein also includes "4'-α-monoglucosylnaringin" (chemical formula 4 below), which has a structure in which glucose is α-linked to the OH group at the 4' position of naringin, and "3",4'-α-diglucosylnaringin" (chemical formula 5 below), which has a structure in which glucose is α-linked to the OH groups at the 3" and 4' positions of naringin, as well as "purunin" (chemical formula 6 below), which has a structure in which β-glucose is linked to the OH group at the 7-position of naringenin, and "narirutin" (chemical formula 7 below), which has a structure in which rutinose (α-rhamnosyl(1→6)glucose) is β-linked to the OH group at the 7-position of narigenin.

[0021] Chemical formula 4:

[0022] Chemical formula 5:

[0023] Chemical formula 6:

[0024] Chemical formula 7:

[0025] Furthermore, the term "glycosylnaringenin" as used herein also includes compounds in which a glycosyl group is further bound to the above-mentioned prunin, naringin, 3"-α-monoglucosylnaringin, narirutin, 4'-α-monoglucosylnaringin, or 3"4'-α-diglucosylnaringin, such as α-maltosylnaringin, α-maltotriosylnaringin, α-maltotetraosylnaringin, α-maltopentaosylnaringin, α-glucosylprunin, α-maltosylprunin, α-maltotriosylprunin, α-maltotetraosylprunin, α-maltopentaosylprunin, α-glucosylnaringenin, α-maltosylnaringenin, α-maltotriosylnaringin, α-maltotetraosylnaringin, α-maltopentaosylnaringin, α-glucosylnaringenin, α-maltosylnaringenin, α-maltotriosylnaringenin, α-maltotetraosylnaringin, and α-maltopentaosylnaringenin.

[0026] These glycosylnaringenins can be produced either enzymatically or by chemical synthesis, preferably by enzymatic methods, or, if necessary, by fermentation or a combination of enzymatic and chemical synthesis methods. When producing glycosyl naringenin, if economic efficiency is an issue, an enzymatic method using a glycosyltransferase is advantageous. For example, as disclosed in Japanese Patent Application Laid-Open Nos. 04-13691 and 2007-284393, a method in which a glycosyltransferase such as α-glucosidase, cyclomaltodextrin glucanotransferase, or α-amylase is allowed to act on naringin in the presence of an α-glucosyl sugar compound such as a partial starch hydrolysate or maltooligosaccharides typically produces a series of 3"-α-glycosyl naringenins in high yield, with the degree of glucose polymerization at the glycosyltransferase moiety ranging from 1 to 5. 3"-α-Monoglucosyl naringin can also be advantageously prepared by allowing glucoamylase to act on this series of 3"-α-glycosyl naringin.

[0027] For example, when glycosyl naringenin contains a glucosyl moiety containing D-glucose as a constituent sugar at the glycosyl transfer site, the degree of glucose polymerization can be appropriately reduced by treating glycosyl naringenin with glucoamylase. On the other hand, the degree of glucose polymerization of the glycosyl group in glycosyl naringenin can also be advantageously increased by treating glycosyl naringenin with a glycosyltransferase such as cyclomaltodextrin glucanotransferase in the presence of a glycosyl donor such as a partial starch hydrolysate. Furthermore, if necessary, it is also possible to add monosaccharides, disaccharides, oligosaccharides, or polysaccharides other than D-glucose to glycosyl naringenin by glycosyl transfer.

[0028] Furthermore, prunin represented by Chemical Formula 6 can be prepared by treating naringin with rhamnosidase to remove rhamnose, as disclosed in, for example, JP 2007-284393 A. On the other hand, narirutin can be prepared, for example, by α-1,6-transferring rhamnose to prunin. Furthermore, these glycosylnaringenins can also be prepared by fermentation, chemical degradation, or synthesis, as needed.

[0029] In the present invention, glycosyl naringenin can be used regardless of its origin, production method, purity, etc., and does not necessarily have to be highly purified. As long as its action and safety are not affected, it may be in the form of a mixture with other substances specific to the production method, or may be partially purified or unpurified. For example, when glycosyl naringenin is prepared by an enzymatic method, the enzymatic reaction solution containing glycosyl naringenin may be used as is.

[0030] As described above, due to its production method, the glycosylnaringenin contained in the composition of the present invention is usually in the form of a composition containing as its main component one or more compounds selected from (1) naringin and α-glycosylnaringin (such as α-glucosylnaringin), which are compounds having a naringenin skeleton, i.e., a glycosylnaringenin mixture, but may also contain trace components such as (2) flavonoids such as diosmin and neopolycin, and (3) salts. The glycosylnaringenin may also contain naringenin, which is its aglycone, to the extent that the desired effects of the present invention are not impaired.

[0031] The glycosyl naringenin that can be used in the composition of the present invention may contain a single compound within the category of glycosyl naringenin described above, or may be a mixture containing two or more compounds within the category of glycosyl naringenin. From the viewpoint of high solubility in water, the composition of the present invention preferably contains α-glycosyl naringin as the glycosyl naringenin, more preferably α-glucosyl naringin as the α-glycosyl naringin, and even more preferably contains one or more α-glucosyl naringin selected from 3"-α-monoglucosyl naringin, 3",4'-α-diglucosyl naringin, and 4'-α-monoglucosyl naringin as the α-glucosyl naringin.

[0032] There is no particular upper limit to the α-glycosyl naringin content per dry solid in the glycosyl naringenin contained in the composition of the present invention, but typically, a content of 99% by mass or less is sufficient for industrially large-scale, inexpensive, and easy provision, and even lower, such as 80% by mass or less for even lower cost, and even lower, such as 60% by mass or less, may be used. However, when the α-glycosyl naringin content per dry solid of the α-glycosyl naringin is low, it will inevitably be used in larger amounts than a composition with a higher content, resulting in poorer handleability. Therefore, the lower limit of the α-glycosyl naringin content is typically 10% by mass or more, preferably 20% by mass or more, more preferably 30% by mass or more, even more preferably 40% by mass or more, and even more preferably 50% by mass or more. The same applies to the α-glucosyl naringin content in glycosyl naringenin.

[0033] In a preferred embodiment, the glycosyl naringenin contained in the composition of the present invention comprises α-glycosyl naringin, and more preferably comprises 3"-α-monoglucosyl naringin as the α-glycosyl naringin. In this case, the preferred content of 3"-α-monoglucosyl naringin in the glycosyl naringenin is typically 10% by mass or more, preferably 20% by mass or more, more preferably 30% by mass or more, even more preferably 40% by mass or more, and even more preferably 50% by mass or more, based on the dry solids. Furthermore, the upper limit of the 3"-α-monoglucosyl naringin content in the glycosyl naringenin contained in the composition of the present invention is basically less than 100% by mass. However, from the perspective of providing the composition of the present invention at a lower cost, a low content of 99% by mass or less, more preferably 70% by mass or less, which can be easily and inexpensively provided in relatively large quantities industrially, may be used.

[0034] Next, component (B) will be described. Pinene, which can be used in the composition of the present invention, has the molecular formula C １０ H １６It is a type of monoterpene represented by the formula: and is found in, for example, turpentine. Pinene includes α-pinene and β-pinene, and α-pinene and β-pinene each exist as d- and l-isomers. The pinene that can be used in the composition of the present invention may be any of these, or may be a mixture. Sabinene is a compound represented by the molecular formula C １０ H １６ It is a type of monoterpene represented by the molecular formula C, and is found in juniper oil, for example. Sabinene exists in the d- and l-forms. The sabinene that can be used in the composition of the present invention may be either of these, or a mixture thereof. Camphene is a compound represented by the molecular formula C １０ H １６ It is a type of monoterpene represented by the formula C, and is found in, for example, rosemary oil and valerian oil. Camphene exists in d- and l-forms. The camphene that can be used in the composition of the present invention may be either of these, or a mixture thereof. Valencene is a monoterpene represented by the molecular formula C １５ H ２４ β-Caryophyllene is a type of sesquiterpene with the molecular formula C １５ H ２４ β-Ionone is a type of sesquiterpene represented by the chemical formula C, and is found, for example, in the essential oils of plants of the Myrtaceae family, clove oil, and cinnamon oil. １３ H ２０ It is represented by O and is also known as β-ionone. β-ionone is found, for example, in the essential oils of plants of the Rutaceae family. It can also be chemically synthesized by condensing citral with acetone and then reacting with an acid. Methyl anthranilate has the molecular formula C ８ H ９ NO ２It is a nitrogen-containing compound represented by the formula C, and is also known as methyl 2-aminobenzoate. Methyl anthranilate is known to be contained in, for example, jasmine and grapes, and can also be chemically synthesized by dehydration condensation of anthranilic acid and methanol. Methyl N-methylanthranilate has the molecular formula C ９ H １１ NO ２ Methyl N-methylanthranilate is a nitrogen-containing compound represented by the formula (I), and is also known as methyl N-methyl-2-aminobenzoate. Methyl N-methylanthranilate is known to be present, for example, in Citrus sinensis oil, and can also be chemically synthesized by dehydration condensation of N-methylanthranilic acid and methanol.

[0035] The above-mentioned pinene, camphene, sabinene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, and methyl N-methylanthranilate that can be used in the present invention may be produced by chemical synthesis or may be obtained by extraction from natural products containing these compounds. The above-mentioned components that can be used in the composition of the present invention may, of course, be isolated from natural products or highly purified components, but are not necessarily isolated and purified components. Instead of isolated and purified components, for example, essential oils obtained from natural products containing pinene, camphene, sabinene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, or methyl N-methylanthranilate can also be used.

[0036] Meanwhile, thymol that can be used in the composition of the present invention is a compound represented by the following chemical formula 8, and has the molecular formula C １０ H １４ Thymol is a type of monoterpene represented by the formula O. Thymol is known to have antibacterial and blood flow improving effects.

[0037] Chemical formula 8:

[0038] Thymol can be produced, for example, by chemical synthesis, or can be obtained by extraction from natural products containing thymol. Natural products containing thymol include Japanese citrus fruits such as yuzu, and herbs such as thyme, oregano, and savory. Thymol is found in large amounts in yuzu, thyme, oregano, and horsemint, for example. While thymol can of course be isolated from these natural products, the thymol that can be used in the composition of the present invention does not necessarily have to be isolated thymol; instead of isolated thymol, for example, essential oils obtained from these natural products can be used.

[0039] Meanwhile, nootkatone that can be used in the composition of the present invention is a compound represented by the following chemical formula 9, and has the molecular formula C １５ H ２２ Nootkatone is a type of sesquiterpene ketone represented by the general formula O. Nootkatone may be either the d-isomer or the l-isomer, or a mixture such as a racemate, and is not particularly limited. Nootkatone is known to have AMPK (AMP-activated protein kinase) activity.

[0040] Chemical formula 9:

[0041] Nootkatone can be produced by chemical synthesis, synthesis using microorganisms, or the like, or can be obtained by extraction from natural products containing nootkatone. Examples of natural products containing nootkatone include grapefruit. Furthermore, the nootkatone that can be used in the composition of the present invention does not necessarily have to be isolated nootkatone. Instead of isolated nootkatone, for example, grapefruit essential oil, which is known to contain relatively large amounts of nootkatone, can also be used.

[0042] Extraction of nootkatone and thymol from natural products can be carried out, for example, by a method that appropriately combines an extraction procedure using water, hot water, aqueous alcohol, organic solvents, etc. with a purification procedure using high performance liquid chromatography, column chromatography, etc., and a distillation procedure. The thymol and / or nootkatone obtained by the above synthesis or extraction is preferably highly purified by removing impurities through single or multiple purification steps, but crude products may also be used as long as the effects of the present invention are achieved.

[0043] The component (B) that can be used in the composition of the present invention may be an isomer or derivative thereof. Examples of derivatives of nootkatone include, but are not limited to, nootkatol, dihydronootkatone, dehydronootkatone, and tetrahydronootkatone.

[0044] On the other hand, isomers of thymol include, for example, carvacrol, and derivatives include, for example, but are not limited to, thymyl acetate, thymol methyl ether, and methylthymol.

[0045] The composition of the present invention contains, as a constituent component, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone. As shown in the experiments described below, a combination of component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone significantly increases GLP-1 secretion. Moreover, this effect is superior to the effect of each component used alone and exceeds the additive effect of each component used alone, which can be said to be a synergistic effect. Among these, when component (B) is thymol and / or nootkatone, a particularly remarkable synergistic effect is exhibited, and therefore thymol and / or nootkatone are particularly suitable for use as component (B). Therefore, a composition containing glycosylnaringenin and thymol and / or nootkatone can be a particularly effective composition for promoting GLP-1 secretion.

[0046] Here, the term "promotion of GLP-1 secretion" in the present invention means that the secretion of GLP-1 from GLP-1-secreting cells is promoted in the presence of the GLP-1 secretion-promoting composition compared to the absence of the composition, and is a concept that includes all of promotion of GLP-1 secretion in the body, promotion of GLP-1 secretion from L cells in the intestinal tract, promotion of an increase in blood GLP-1 concentration associated with GLP-1 secretion in the body, maintenance of an increased GLP-1 concentration, or inhibition of a decrease in an increased GLP-1 concentration, i.e., stabilization of blood GLP-1 concentration.

[0047] As described above, GLP-1 is primarily secreted from L cells present in the intestinal tract, and therefore, GLP-1 secretion can be promoted by orally administering or ingesting a composition comprising component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone. GLP-1 is known to act, for example, via GLP-1 receptors expressed in many organs and tissues, such as pancreatic α cells, pancreatic β cells, the central nervous system, and the stomach, to inhibit glucagon secretion from pancreatic α cells, promote insulin secretion from pancreatic β cells, and act on the central nervous system. Therefore, in a preferred embodiment, the composition of the present invention that promotes GLP-1 secretion can be used to control various physical conditions, for example, to prevent and / or improve lifestyle-related diseases such as obesity and diabetes, to improve insulin resistance, to suppress appetite in the central nervous system, to delay gastric emptying in the digestive tract, to promote postprandial digestion, to improve stomach heaviness and gastric acid secretion ability, or to enhance energy metabolism.

[0048] The amount of component (A), i.e., glycosylnaringenin, in the composition of the present invention is not particularly limited, but the total glycosylnaringenin content in the composition is usually 0.0001% by mass or more, preferably 0.001% by mass or more, preferably 0.002% by mass or more, more preferably 0.02% by mass or more, and even more preferably 0.2% by mass or more.

[0049] In the composition of the present invention, the blending ratio of component (A) glycosylnaringenin to component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone is not limited as long as the desired effects of the present invention can be obtained. However, from the viewpoint of the synergistic effect of component (A) and component (B), The blending ratio, in terms of the molar ratio (A / B) of the component (A) to the component (B), is, for example, 10,000:1 to 1:10, preferably 4,000:1 to 1:10, more preferably 3,731:1 to 1:10, more preferably 1,000:1 to 1:10, more preferably 1,000:1 to 1:1, even more preferably 200:1 to 1:1, still more preferably 100:1 to 1:1, still more preferably 50:1 to 1:1, and particularly preferably 10:1 to 1:1. Furthermore, when the component (A) and the component (B) are thymol, from the viewpoint of a synergistic effect, the blending ratio, in terms of the molar ratio (A / B) of the component (A) to the component (B), is, for example, 10,000:1 to 1:10, preferably 4,000:1 to 1:10, more preferably 3,731:1 to 1:10, more preferably 1,000:1 to 1:10, more preferably 1,000:1 to 1:5, more preferably 500:1 to 1:5, even more preferably 200:1 to 1:1, and still more preferably 100:1 to 1:1. When the component (A) and the component (B) are nootkatone, from the viewpoint of a synergistic effect, the blending ratio, in terms of the molar ratio (A / B) of the component (A) to the component (B), is, for example, 1000:1 to 1:5, preferably 500:1 to 1:5, more preferably 333:1 to 1:5, more preferably 200:1 to 1:5, more preferably 100:1 to 1:5, even more preferably 50:1 to 1:5, even more preferably 10:1 to 1:5, even more preferably 3:1 to 1:5, still more preferably 1:1 to 1:5, and particularly preferably 10:1 to 1:1. Incidentally, the above ranges expressed using "to" include the upper and lower limits.

[0050] The dosage, administration route, administration interval, intake amount, or intake interval of the composition for promoting GLP-1 secretion of the present invention can be appropriately determined depending on the body weight, sex, age, condition, or other factors of the subject or user of administration, and the intake amount or administration amount is, for example, 0.1 to 500 mg, preferably 1 to 300 mg, more preferably 2 to 200 mg, and even more preferably 5 to 150 mg of glycosylnaringenin per day for an adult (body weight 60 kg). On the other hand, when component (B) contains one or more selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, and N-methylmethyl anthranilate, the intake or administration amount thereof is, for example, 0.0001 to 10 mg, preferably 0.0005 to 5 mg, more preferably 0.001 to 2 mg, and even more preferably 0.01 to 1 mg, of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, or N-methylmethyl anthranilate per day for an adult (body weight 60 kg). Furthermore, when component (B) contains thymol, the intake or administration amount thereof is, for example, 0.001 to 10 mg, preferably 0.05 to 5 mg, more preferably 0.01 to 2 mg, and even more preferably 0.01 to 1 mg, of thymol per day for an adult (body weight 60 kg). Furthermore, when component (B) contains nootkatone, the intake or administration amount thereof is typically, for example, 1 to 2,000 mg, more preferably 2 to 1,000 mg, and even more preferably 5 to 500 mg, of nootkatone per day for an adult (body weight 60 kg). In the present invention, it is preferred to administer or ingest such an amount once or multiple times a day, preferably once a day.

[0051] The composition of the present invention, which contains component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone, may be formulated in a single dosage form containing component (A) and component (B) as a combination agent, or may be formulated individually and used simultaneously or separately at intervals.

[0052] Furthermore, the composition of the present invention has excellent water solubility and can be incorporated into a variety of products. Specifically, it can be advantageously used as a material or formulation to be incorporated into flavorings, foods and beverages, supplements, pharmaceuticals, quasi-drugs, feed, etc. When administered to or ingested by animals including humans, flavorings, foods and beverages, supplements, pharmaceuticals, quasi-drugs, feed, etc., containing the composition of the present invention exhibit an excellent GLP-1 secretion-promoting effect, and therefore can be used extremely advantageously. Needless to say, the composition of the present invention may be used as is as a flavoring, foods and beverages, supplements, pharmaceuticals, quasi-drugs, feed, etc.

[0053] Foods, beverages, or supplements that can be formulated with the composition of the present invention include foods that claim to promote postprandial GLP-1 secretion and are permitted to label as such, as necessary (foods for specified health uses, foods with functional claims). Foods permitted to label as having a function can be distinguished from general foods. Examples of such labels include "improves insulin resistance and lowers blood glucose levels" and "suppresses the rise in postprandial blood glucose levels."

[0054] The food and drink to which the composition of the present invention can be blended may basically be any type and is not particularly limited. There is also no particular limitation on the form, and the food and drink may be in any form, such as a liquid (including syrup, milk, and suspension), fluid, gel, semi-solid, solid, or powder, or may be a food and drink that is prepared just before use in a liquid, fluid, gel, semi-solid, solid, powder, or other form. Specific examples include alcoholic beverages such as synthetic alcohol, brewed alcohol, sake, fruit wine, happoshu, beer, liqueur, chuhai, and medicinal alcohol; carbonated drinks, soft drinks, tonic water, dairy drinks, smoothies, vegetable juice, fruit juice drinks, sports drinks, vinegar drinks, soy milk drinks, iron-containing drinks, lactic acid bacteria drinks, green tea, black tea, herbal tea, cocoa, coffee, non-alcoholic drinks, and energy drinks; staple foods such as rice, porridge, mochi, and bread; noodles such as udon, soba, ramen, and spaghetti; soups such as miso soup and vegetable soup; dairy products such as yogurt and cheese; meat products such as sausage and ham; fish products such as kamaboko, chikuwa, hanpen, and fish sausage; and seafood. canned goods, dried fish and other processed seafood products; foods for cooking such as nursing care food and liquid food and frozen foods made by freezing these; sweets such as soft candy, hard candy, gummies, jellies, cookies, soft cookies, rice crackers, gyuhi (soft rice cakes), mochi (rice cakes), mousse, bavarois, biscuits, chocolate, chewing gum, caramel, fruit paste, jam, marmalade, cereal bars, protein bars and energy bars; frozen desserts such as ice cream, sorbet and gelato; and various seasonings and processed foods such as miso, powdered miso, soy sauce, powdered soy sauce, mayonnaise, dressing, vinegar, noodle soup, sauce, tomato sauce, curry roux, soup base and compound seasonings.

[0055] Furthermore, foods and beverages that can be blended with the composition of the present invention may contain additives that are acceptable from the standpoint of food hygiene, as necessary. Examples of such additives include sweeteners, acidulants, bittering agents, seasonings, flavorings, thickening polysaccharides, emulsifiers, preservatives, disinfectants or antibacterial agents, pH adjusters, isotonicity agents, chelating agents, stabilizers, antioxidants, colorants, bulking agents, flow-improving agents, excipients, binders, disintegrants, solvents, softeners, oils, fillers, foaming agents, antifoaming agents, nutrients, favorite foods, flavoring substances, medicinal substances, and the like, as well as active ingredients other than component (A) glycosylnaringenin and component (B) α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone that can be contained in the composition of the present invention. Since naringin, 3′-α-monoglucosylnaringin, 3′,4′-α-diglucosylnaringin, and 4′-α-monoglucosylnaringin contained in glycosylnaringenin have a bitter taste, the composition of the present invention can be suitably used as a bittering agent in one embodiment.

[0056] On the other hand, when the composition of the present invention is incorporated into a food or beverage, there is no particular limitation on the content of glycosylnaringenin in the food or beverage containing the composition of the present invention, and the content can be adjusted appropriately depending on the form of use. There is no particular limitation on the lower limit, but it is preferably 1 ppm or more, more preferably 5 ppm or more, and even more preferably 10 ppm or more. There is no particular limitation on the upper limit, but it is preferably 2000 ppm or less, more preferably 500 ppm or less, and even more preferably 200 ppm or less. Similarly, there is no particular limitation on the content of sabinene, valencene, β-ionone, methyl N-methylanthranilate, or thymol in a food or beverage containing the composition of the present invention, and the content can be adjusted appropriately depending on the form of use. There is no particular limitation on the lower limit, but it is preferably 0.001 ppm or more, more preferably 0.01 ppm or more, and even more preferably 0.1 ppm or more. There is no particular upper limit, but it is preferably 100 ppm or less, more preferably 10 ppm or less, and even more preferably 5 ppm or less. There is no particular limit to the content of α-pinene, β-pinene, camphene, β-caryophyllene, methyl anthranilate, or nootkatone in a food or beverage containing the composition of the present invention, and the content can be adjusted appropriately depending on the form of use. There is no particular lower limit, but it is preferably 0.001 ppm or more, more preferably 0.01 ppm or more, even more preferably 0.1 ppm or more, and even more preferably 0.5 ppm or more. There is no particular upper limit, but it is preferably 50,000 ppm or less, more preferably 500 ppm or less, even more preferably 50 ppm or less, and even more preferably 30 ppm or less.

[0057] On the other hand, the supplements that can be formulated with the composition of the present invention not only refer to dietary supplements and functional foods for supplementing nutrients, but also to health supplements, foods for specified health uses, and foods with functional claims that have functions useful for maintaining, restoring, or improving health. There are no particular limitations on the form of such supplements, and they can be, for example, liquid (including syrup, milk, and suspension), gel, paste, tablet, pill, capsule (including hard capsule, soft capsule, and microcapsule), powder, granule, fine granule, lozenge, etc. Supplements in these forms can be manufactured according to conventional methods using appropriate excipients, dispersants, disintegrants, binders, lubricants, capsule bases, coating agents, etc. Furthermore, supplements that can be formulated with the composition of the present invention may contain additives that are acceptable in terms of food hygiene or ordinary health food ingredients. The additives that are acceptable in terms of food hygiene have already been described in the explanation of foods and beverages.

[0058] On the other hand, when the composition of the present invention is incorporated into a supplement, there is no particular limitation on the content of glycosylnaringenin in the supplement containing the composition of the present invention, and the content can be adjusted appropriately depending on the form of use. There is no particular limitation on the lower limit, but it is preferably 1 ppm or more, more preferably 10 ppm or more, even more preferably 50 ppm or more, and even more preferably 100 ppm or more. There is no particular limitation on the upper limit, but it is preferably 50% by mass or less, more preferably 30% by mass or less, even more preferably 10% by mass or less, and even more preferably 5% by mass or less. Furthermore, there is no particular limitation on the content of sabinene, valencene, β-ionone, N-methylanthranilate methyl, or thymol in a supplement containing the composition of the present invention, and the content can be adjusted appropriately depending on the form of use. There is no particular limitation on the lower limit, but it is preferably 0.001 ppm or more, more preferably 0.01 ppm or more, even more preferably 0.05 ppm or more, and even more preferably 1 ppm or more. On the other hand, there is no particular upper limit, but it is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 1% by mass or less, and even more preferably 0.1% by mass or less. Furthermore, there is no particular limit on the content of α-pinene, β-pinene, camphene, β-caryophyllene, methyl anthranilate, or nootkatone in a supplement containing the composition of the present invention, and the content can be adjusted appropriately depending on the form of use. There is no particular lower limit, but it is preferably 0.001 ppm or more, more preferably 0.01 ppm or more, even more preferably 0.05 ppm or more, and even more preferably 1 ppm or more. On the other hand, there is no particular upper limit, but it is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 1% by mass or less, and even more preferably 0.1% by mass or less.

[0059] Next, the fragrance that can be blended with the composition of the present invention refers to a substance that imparts a fragrance to foods, beverages, cosmetics, etc., and there is no particular limitation on the type. For example, fragrances are classified into natural fragrances, synthetic fragrances, and blended fragrances obtained by blending one or more natural fragrances and / or synthetic fragrances depending on their origin. The composition of the present invention can be suitably blended with any of these, regardless of whether they are natural fragrances, synthetic fragrances, or blended fragrances. Natural fragrances include plant-based fragrances obtained from plant-derived raw materials and animal-based fragrances obtained from animal-derived raw materials, such as musk, civet, castoreum, and ambergris. Natural fragrances such as plant-based fragrances and animal-based fragrances can be obtained by manufacturing methods such as pressing, distillation, and extraction. On the other hand, synthetic fragrances include isolated fragrances isolated from animal and vegetable oils by distillation, extraction, etc., semi-synthetic fragrances produced from isolated fragrances, and synthetic fragrances in the narrow sense produced by chemical synthesis, mainly using petrochemical-derived chemical products as raw materials.

[0060] Among flavors, flavors used in foods and beverages are called "food flavors" or "flavors" (hereinafter, in this specification, flavors used in foods and beverages will be simply referred to as "food flavors"), while flavors used in cosmetics are called "fragrances." The composition of the present invention exhibits a GLP-1 secretion-promoting effect, and is therefore suitable for use as a food flavor, which is a flavor used primarily in foods and beverages that are taken orally.

[0061] The flavoring agent that can be blended with the composition of the present invention is provided in a form suitable for the intended use, and the form is not particularly limited. For example, when the flavoring agent that can be blended with the composition of the present invention is a food flavoring agent, the flavoring agent can be in the form of, but not limited to, a water-soluble flavoring agent, an oil-soluble flavoring agent, an emulsified flavoring agent, a powdered flavoring agent, or the like, depending on the type of food or beverage, which may be in various forms from liquid to solid.

[0062] Furthermore, when the composition of the present invention is blended into a fragrance, there are no particular limitations on the blending method or timing, and it can be blended at any stage in the fragrance preparation process.

[0063] The water-soluble flavoring refers to a water-soluble liquid flavoring, and includes, for example, essences, recovered flavors, extracts, etc. The water-soluble flavoring can be used in foods and beverages, such as foods with a high moisture content, beverages, jellies, frozen desserts, etc. The amount of flavoring to be added to foods and beverages varies depending on the type, dosage form, or intended use of the food and beverage, but typically ranges from 0.001 to 5%, preferably from 0.01 to 1%, for example.

[0064] Essences are water-soluble fragrances in the form of fragrance components dissolved in a water-soluble solvent such as alcohol, propylene glycol, or glycerin. They are prepared, for example, by extracting and dissolving a material (flavor base) containing fragrance components such as essential oils obtained by steam distillation or pressing from natural products such as flowers, buds, leaves, and stems, with aqueous ethyl alcohol (ethanol) or the like. As described above, there are no particular limitations on the method or timing of blending the composition of the present invention into a fragrance. However, when blending the composition of the present invention to prepare an essence, for example, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone can be added and dissolved in advance to the aqueous alcohol used for extraction, or component (A) and component (B) can be added and dissolved in the extract obtained by extraction treatment, thereby obtaining an essence containing component (A) and component (B). Here, component (B) may be added simultaneously with component (A) (glycosylnaringenin) or separately. Alternatively, the component (B) may be extracted into a flavoring material such as a flavoring material containing the component (B), fruit juice, vegetable juice, plant material, etc. When two or more components (B) are used, the two or more components (B) may be added simultaneously or separately.

[0065] Incidentally, the ethanol content of the aqueous ethanol used in preparing the essences is not particularly limited, but is preferably 20 to 99 w / w%, more preferably 30 to 80 w / w%, and even more preferably 40 to 70 w / w%. The aqueous ethanol may contain components other than water and ethanol, such as glycerin and propylene glycol.

[0066] Water-soluble recovered aromas are water-soluble fragrances obtained by concentrating, for example, fruit juices, vegetable juices, plant materials, meat and seafood extracts, etc., by evaporation, membrane concentration, or the like. When the composition of the present invention is incorporated into a recovered aroma, it can be incorporated, for example, by directly adding and dissolving component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone to the resulting recovered aroma, thereby obtaining a recovered aroma with an even more excellent aroma. Component (B) may be added simultaneously with component (A) (glycosylnaringenin) or separately. Furthermore, when two or more types of component (B) are used, the two or more types of component (B) may be added simultaneously or separately.

[0067] Extracts are water-soluble fragrances obtained by extracting animal or plant materials with water or a water-soluble aqueous solvent having a water content of about 10 to about 90%, such as aqueous methanol, aqueous ethanol, aqueous acetone, aqueous glycerin, aqueous ethylene glycol, aqueous propylene glycol, etc. When the composition of the present invention is incorporated into extracts, etc., for example, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone may be added in advance to the water-soluble aqueous solvent that serves as the extraction solvent, or component (A) and component (B) may be added to the extract obtained by extraction treatment, or component (A) and component (B) may be added to a concentrate obtained by removing the solvent from the extract. The components (A) and (B) may be added simultaneously or separately. When two or more components (B) are used, the two or more components (B) may be added simultaneously or separately.

[0068] On the other hand, oil-soluble flavorings are flavorings that are dissolved in an oil-soluble solvent such as vegetable oil, and can be used in foods and beverages such as foods that are compatible with oily foods, breads, chocolates, margarines, cooked foods, etc. The amount of oil-soluble flavoring to be added to foods and beverages varies depending on the type, dosage form, or intended use of the food and beverage, but typically ranges from 0.01 to 10%, preferably from 0.05 to 5%, for example.

[0069] Oil-soluble fragrances can be prepared, for example, by directly extracting plant materials containing fragrance components with fats and oils, or by dissolving the fragrance in fats and oils, propylene glycol, glycerin, or the like. When the composition of the present invention is incorporated into an oil-soluble fragrance, component (A) glycosyl naringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methyl methyl anthranilate, thymol, and nootkatone can be incorporated at any stage. By incorporating glycosyl naringenin into an oil-soluble fragrance, a fragrance with excellent fragrance stability and heat resistance can be obtained. Component (B) may be added simultaneously with component (A) or separately. Alternatively, a fragrance containing component (B), fruit juice, vegetable juice, plant material, or the like may be used as a raw material. The components (A) and (B) may be added simultaneously or separately. When two or more components (B) are used, the two or more components (B) may be added simultaneously or separately.

[0070] Emulsified flavorings are flavorings in the form of fragrance components dispersed in water using an emulsifier, and can be used in foods and beverages, for example, beverages, seasonings such as soups, sauces, and dressings, frozen desserts, desserts, retort pouch foods, processed meat foods, processed seafood foods, etc. The amount of emulsified flavoring to be added to foods and beverages varies depending on the type, dosage form, or intended use of the food and beverage, but typically ranges from 0.001 to 5%, preferably from 0.01 to 1%, for example.

[0071] Emulsified fragrances can be produced, for example, by dispersing an oil phase containing an oil-soluble fragrance component or the like into an aqueous phase containing an emulsifier using the shear force of an emulsifier. When preparing an emulsified fragrance by blending the composition of the present invention, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone can be added and dissolved in the aqueous phase before emulsification, or components (A) and (B) can be added and dissolved in the resulting emulsion composition. However, adding and dissolving component (A) in the aqueous phase before emulsification can produce an emulsified fragrance with excellent emulsion stability. Component (B) can be added simultaneously with component (A) or separately. Alternatively, a flavoring agent containing the component (B), fruit juice, vegetable juice, plant material, etc. may be used as a raw material. When two or more components (B) are used, the two or more components (B) may be added simultaneously or separately.

[0072] The emulsified flavoring may contain other components in addition to the fragrance component in its oil phase and / or aqueous phase. There are no particular limitations on the components to be incorporated into the oil phase, but oil-soluble components are preferred. Examples of such components include oil-soluble natural pigments such as β-carotene, paprika color, annatto color, chlorophyll, and marigold color; fat-soluble vitamins such as cod liver oil, vitamin A, vitamin A oil, vitamin D3, vitamin B2 butyrate ester, and natural vitamin E mixture; animal and vegetable fats and oils such as soybean oil, rapeseed oil, corn oil, olive oil, palm oil, safflower oil, sunflower oil, rice bran oil, beef tallow, lard, and fish oil; vegetable resins such as rosin, copal, dammar, elemi, and ester gum; medium-chain saturated fatty acid triglycerides having 6 to 12 carbon atoms; and specific gravity adjusters such as SAIB (sucrose diacetate hexaisobutyrate). On the other hand, there are no particular restrictions on the components to be blended in the aqueous phase, but water-soluble components are preferred, and examples of such components include emulsifiers such as glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, Quillaja saponin, and lecithin, water-soluble polysaccharides such as gum arabic and soybean polysaccharides, polyhydric alcohols such as glycerin, propylene glycol, sorbitol, and sugar alcohols, antioxidants such as ascorbic acid, etc. The oil phase and aqueous phase are usually prepared separately in advance and then mixed and emulsified.

[0073] On the other hand, powdered flavorings are flavorings in powder form, and can be used in foods and beverages, such as beverages, powdered beverages, desserts, chewing gum, candies, chocolates, tablet candies, noodles, snacks, processed seafood foods, retort foods, etc. The amount of powdered flavoring to be added to foods and beverages varies depending on the type, dosage form, or intended use of the food and beverage, but is preferably in the range of 0.01 to 5%, more preferably 0.1 to 3%, for example.

[0074] Powdered flavors are typically obtained by emulsifying an oil-soluble flavor or the like using an appropriate emulsifier or surfactant, adding an excipient, and homogenizing the mixture, or by powdering a solution in which a water-soluble flavor is uniformly dispersed in an appropriate aqueous coating agent / excipient solution using a powdering method such as spray drying, vacuum drying, or freeze drying. Also known are powders of flavors adsorbed onto lactose, trehalose, maltose, porous dextrin, modified starch, isomaltodextrin, etc., and powders of powdered flavors simply mixed with powder bases such as lactose, trehalose, maltose, and starch, and these are also included in the powdered flavors referred to in this specification. If necessary, the powdered flavor may be subjected to secondary processing using a granulation method such as tumbling granulation, fluidized bed granulation, mixing / stirring granulation, compression molding granulation, extrusion granulation, or hot melt granulation, or a wax coating method.

[0075] In a preferred embodiment, when the composition of the present invention is formulated to prepare a powdered flavor, component (A) glycosylnaringenin and component (B) at least one selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methyl-methyl anthranilate, thymol, and nootkatone can be added to an excipient beforehand, or component (A) can be blended with the resulting powdered flavor. Pre-addition of component (A) to an excipient can result in a powdered flavor that is less susceptible to oxidation over time and has excellent stability. Component (B) can be added simultaneously with component (A) or separately. Alternatively, flavors containing component (B), fruit juice, vegetable juice, plant-derived materials, etc., can be used as raw materials. Furthermore, when two or more types of component (B) are used, the two or more types of component (B) can be added simultaneously or separately.

[0076] There is no particular restriction on the lower limit of the glycosyl naringenin content in the fragrance obtained as described above, but it is preferably 1 ppm or more, more preferably 10 ppm or more, even more preferably 100 ppm or more, and even more preferably 1000 ppm or more. On the other hand, there is no particular restriction on the upper limit of the glycosyl naringenin content, but it is preferably 99.9% by mass or less, more preferably 50% by mass or less, even more preferably 10% by mass or less, and even more preferably 5% by mass or less. There is no particular restriction on the lower limit of the content of sabinene, valencene, β-ionone, methyl N-methylanthranilate, or thymol in the fragrance, but it is preferably 0.01 ppm or more, more preferably 0.1 ppm or more, even more preferably 1 ppm or more, and even more preferably 3 ppm or more. There is no particular upper limit to the content of sabinene, valencene, β-ionone, methyl N-methylanthranilate, or thymol in the fragrance, but it is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 1% by mass or less, and still more preferably 0.3% by mass or less. There is no particular lower limit to the content of α-pinene, β-pinene, camphene, β-caryophyllene, methyl anthranilate, or nootkatone in the fragrance, but it is preferably 0.01 ppm or more, more preferably 0.1 ppm or more, even more preferably 1 ppm or more, and still more preferably 2 ppm or more. There is no particular upper limit to the content of α-pinene, β-pinene, camphene, β-caryophyllene, methyl anthranilate, or nootkatone in the fragrance, but it is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and still more preferably 1% by mass or less.

[0077] On the other hand, pharmaceuticals or quasi-drugs that can be formulated with the composition of the present invention may be pharmaceuticals or quasi-drugs that are applicable to humans or other mammals (e.g., rats, mice, rabbits, sheep, pigs, cattle, cats, dogs, monkeys, etc.) The method of administration is not particularly limited and may be either oral or parenteral administration, and the administration route can be appropriately selected depending on the species, age, weight, etc. of the subject to which the composition of the present invention is to be administered.

[0078] There are no particular limitations on the form of the pharmaceutical or quasi-drug that can be formulated with the composition of the present invention, and it may be in any form, for example, a liquid (including syrup, milk, and suspension), fluid, gel, semi-solid, solid, tablet, round, capsule (including hard capsule, soft capsule, and microcapsule), powder, granule, fine granule, or lozenge. Furthermore, by preparation just before use, it may be in the form of a liquid (including syrup, milk, and suspension), fluid, gel, semi-solid, solid, tablet, round, capsule (including hard capsule, soft capsule, and microcapsule), powder, granule, fine granule, lozenge, etc. Specific dosage forms, for example, for oral administration, include solids such as tablets, coated tablets, granules, powders, pills, lozenges, and capsules (including hard capsules, soft capsules, and microcapsules); and liquids such as elixirs, syrups, and suspensions, but are not limited thereto. On the other hand, dosage forms for parenteral administration are not particularly limited, but examples include injections, transdermal preparations, enteral preparations, drip infusions, external preparations, suppositories, and the like.

[0079] Pharmaceuticals or quasi-drugs that can be formulated with the composition of the present invention can contain a pharmaceutically acceptable base or carrier, a pharmaceutically acceptable additive, and physiologically active ingredients or pharmacologically active ingredients other than the active ingredients that the composition of the present invention can contain (i.e., glycosylnaringenin, α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methylmethyl anthranilate, thymol, and nootkatone).

[0080] Examples of physiologically active ingredients or pharmacologically active ingredients that can be incorporated into the drug or quasi-drug of the present invention include, but are not limited to, antibiotic preparations such as penicillin, erythromycin, chloramphenicol, tetracycline, streptomycin, and kanamycin sulfate; vitamin preparations such as thiamine, riboflavin, L-ascorbic acid, liver oil, carotenoids, ergosterol, and tocopherol; enzyme preparations such as lipase, esterase, urokinase, protease, and β-amylase; extract preparations such as ginseng extract, soft-shelled turtle extract, chlorella extract, aloe extract, and propolis extract; hormone-containing solutions such as macrophage migration inhibitory factor, colony-stimulating factor, insulin, growth hormone, prolactin, erythropoietin, and egg-stimulating hormone; and biological preparations.

[0081] The composition of the present invention can also be incorporated into feed for livestock, poultry, pets, etc. Examples of such feed include livestock feed for cattle, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, rats, mice, etc.; and pet food for dogs, cats, small birds, etc. The form of the feed is not particularly limited, and can be, for example, liquid, powder, pellets, flakes, or mash. The feed may further contain other feed ingredients, such as meat, protein, grains, bran, lees, sugars, vegetables, vitamins, minerals, gelling agents, shape-retaining agents, pH adjusters, seasonings, preservatives, nutritional supplements, etc., as well as active ingredients other than the composition of the present invention, as needed.

[0082] On the other hand, the composition of the present invention may contain other ingredients, such as sweeteners, acidulants, bittering agents, spices, seasonings, food flavorings, thickening polysaccharides, emulsifiers, preservatives, bactericides or antibacterial agents, pH adjusters, isotonicity agents, chelating agents, stabilizers, antioxidants, colorants, vitamins, excipients, etc., as well as active ingredients other than the composition of the present invention, depending on the intended use. It is also optional to provide the composition in the form of an intermediate product or premix in which these ingredients are combined. When the composition of the present invention is provided as a flavoring, food or beverage, supplement, quasi-drug, pharmaceutical, feed, or an intermediate product or premix thereof, other ingredients that can be blended depending on the intended use include, but are not limited to, the following examples.

[0083] Examples of sweeteners (including sugars) include monosaccharides, disaccharides, oligosaccharides, sugar alcohols, and high-intensity sweeteners. Specific examples include monosaccharides such as glucose, fructose, galactose, arabinose, xylose, rhamnose, ribose, isomerized liquid sugar, and N-acetylglucosamine; disaccharides such as sucrose, maltose, trehalose, palatinose (isomaltulose), lactulose, and lactose; α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, isomaltooligosaccharides (isomaltose, isomaltotriose, panositol); sugars, etc.), α-glycosyltrehalose, α-glycosylsucrose, oligo-N-acetylglucosamine, lactosucrose, galactosyllactose, galactopyranosyl (β1-3) galactopyranosyl (β1-4) glucopyranose, galactopyranosyl (β1-3) glucopyranose, galactopyranosyl (β1-6) galactopyranosyl (β1-4) glucopyranose, galactopyranosyl (β1-6) glucopyranose, xylose Oligosaccharides (xylotriose, xylobiose, etc.), gentiooligosaccharides (gentiobiose, gentiotriose, gentiotetraose, etc.), stachyose, theandeoligosaccharides, nigerooligosaccharides (nigerose, etc.), palatinose oligosaccharides, palatinose syrup, fucose, fructooligosaccharides (kestose, nystose, etc.), fructofuranosyl nystose, polydextrose, maltosyl β-cyclodextrin, maltooligosaccharides (malto triose, tetraose, pentaose, hexaose, heptaose, etc.), oligosaccharides such as raffinose, erlose, soybean oligosaccharides, invert sugar, and starch syrup; sugar alcohols such as sorbitol, maltitol, isomaltitol, maltotriitol, erythritol, xylitol, glycerol, palatinite, mannitol, lactitol, reduced isomaltooligosaccharides, reduced xylooligosaccharides, reduced gentiooligosaccharides, reduced maltose starch syrup, and reduced starch syrup;High-intensity sweeteners such as dihydrochalcone, α-glucosyltransferase-treated stevia, aspartame, acesulfame potassium, alitame, advantame, neotame, L-aspartyl-L-phenylalanine methyl ester, thaumatin, monellin, saccharin, cyclamate, sucralose, stevia extract, stevia powder, licorice extract (glycyrrhizin), dulcin, Tenryocha extract, Neiseria berry extract, fructosyltransferase-treated stevia, Luo Han Guo extract, enzyme-treated licorice, and enzyme-decomposed licorice; other examples include honey, maple sugar, fruit juice, and fruit juice concentrate;

[0084] Examples of acidulants include benzoic acid, adipic acid, sorbic acid, citric acid, trisodium citrate, glucono-delta-lactone, gluconic acid, potassium gluconate, sodium gluconate, succinic acid, monosodium succinate, disodium succinate, sodium acetate, DL-tartaric acid, L-tartaric acid, sodium DL-tartrate, sodium L-tartrate, lactic acid, sodium lactate, acetic acid, fumaric acid, monosodium fumarate, DL-malic acid, sodium DL-malate, phosphoric acid, malic acid, itaconic acid, α-ketoglutaric acid, phytic acid, disodium dihydrogen pyrophosphate, and sodium acid metaphosphate, as well as vinegar and fruit juice.

[0085] Examples of bittering agents include isoalpha-bitter acid, caffeine (extract), quinine, mulberry, Coriolus versicolor extract, Cinchona extract, Phellodendron amurense extract, Gentian extract, spice extract, Jamaican cassia extract, theobromine, bitter oak extract, Artemisia absinthium extract, tea extract, Japanese knotweed extract, Agaricus blazei extract, Borax blazei, methylthioadenosine, Ganoderma lucidum extract, olive tea, bitter orange extract, hop extract, and Artemisia princeps extract.

[0086] Examples of spices include ajowan, angelica, anise, turmeric, onion, allspice, oregano, garlic, cardamom, caraway, cloves, capers, pepper (red pepper, black pepper, white pepper, green pepper, etc.), saffron, ginger, white mustard, coriander, sage, Japanese pepper, cinnamon, star anise, horseradish, celery, sesame, thyme, tarragon, turmeric, chili pepper, chives, tangerine, chili pepper, nutmeg, basil, paprika, parsley, vanilla, peppermint, marjoram, mustard, myoga, mace, lemongrass, rosemary, and laurel.

[0087] Examples of seasonings include L-asparagine, L-aspartic acid, sodium L-aspartate, DL-alanine, L-alanine, L-arginine, L-arginine-L-glutamate, L-isoleucine, glycine, L-glutamine, L-glutamic acid, potassium L-glutamate, calcium L-glutamate, sodium L-glutamate, magnesium L-glutamate, L-cystine, L-serine, taurine (extract), L-tyrosine, and L-tea. threonine, L-valine, L-histidine, L-histidine hydrochloride, L-hydroxyproline, L-phenylalanine, L-proline, betaine, DL-methionine, L-methionine, L-lysine, L-lysine-L-aspartate, L-lysine hydrochloride, L-lysine-L-glutamate, L-leucine, 5'-inosinic acid disodium salt, 5'-uridylic acid disodium salt, 5'-guanidinium carbonate Disodium citrate, 5'-cytidylate disodium, 5'-ribonucleotide calcium, 5'-ribonucleotide disodium, monopotassium citrate, tripotassium citrate, calcium citrate, trisodium citrate, succinic acid, monosodium succinate, disodium succinate, sodium acetate (crystalline), sodium acetate (anhydrous), DL-sodium hydrogen tartrate, L-sodium hydrogen tartrate, DL-sodium tartrate, L-sodium tartrate, calcium lactate, sodium lactate, monosodium fumarate, DL-sodium malate, potassium chloride, low-sodium chloride brine solution, crude seawater potassium chloride, whey salt, tripotassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate (crystalline), disodium hydrogen phosphate (anhydrous), sodium dihydrogen phosphate (crystalline), sodium dihydrogen phosphate (anhydrous), trisodium phosphate (crystalline), trisodium phosphate (anhydrous), chlorella extract, and the like.

[0088] Examples of food flavors include citrus flavors such as orange, lemon, lime, grapefruit, mandarin, and tangerine, shiikuwasha, yuzu, mandarin, citrus, bergamot, iyokan, kabosu, bitter orange, pomelo, kumquat, sudachi, and ponkan; fruit flavors such as apple, banana, cherry, grape, melon, peach, pineapple, plum, cranberry, and strawberry; bean flavors such as vanilla, coffee, cocoa, and chocolate; mint flavors such as peppermint, spearmint, and horsemint; spice flavors such as allspice, cinnamon, and nutmeg; nut flavors such as almond, peanut, and walnut; seafood flavors such as crab, shrimp, and other seafood; and various other flavors of vegetables, grains, seaweed, etc.

[0089] Examples of thickening polysaccharides include alginic acid and its salts (e.g., sodium alginate, etc.), propylene glycol alginate, calcium carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose, sodium polyacrylate, almond gum, gum arabic, xanthan gum, galactomannans (e.g., locust bean gum, guar gum, tara gum, etc.), psyllium seed gum, artemisia seed gum, sesbania gum, tamarind seed gum, gellan gum, deacylated gellan gum, native gellan gum, carrageenan, glucomannan, konjac flour, macrophomopsis gum, arabinogalactan, elemi resin, karaya gum, dammar resin, tragacanth gum, peach resin, amaryllis seed gum, and oak. Examples of suitable cellulose gums include agar, triacanthos gum, agar, gelatin, pectin (e.g., HM pectin, LM pectin, etc.), pullulan, curdlan, tragacanth gum, ghatti gum, arabinogalactan, karaya gum, chitin, welan gum, starches (e.g., starch, sodium carboxymethyl starch, carboxymethyl starch, hydroxypropyl starch, pregelatinized starch, phosphate cross-linked starch, starch octenyl succinate, starch acetate, etc.), dextrins (e.g., branched dextrin, isomaltodextrin, polydextrose, indigestible dextrin, etc.), dextran, soybean polysaccharides, crystalline cellulose and preparations thereof, powdered cellulose and preparations thereof, chitin, chitosan, glucosamine, oligoglucosamine, PGA, porphyran, furcellaran, and fucoidan.

[0090] Examples of emulsifiers include glycerin fatty acid esters, glycerin acetate fatty acid esters, glycerin lactate fatty acid esters, glycerin succinate fatty acid esters, glycerin diacetyltartarate fatty acid esters, sorbitan fatty acid esters, sucrose fatty acid esters, sucrose acetate isobutyrate esters, polyglycerin fatty acid esters, polyglycerin condensed ricinoleate esters, propylene glycol fatty acid esters, calcium stearoyl lactylate, sodium stearoyl lactylate, polyoxyethylene sorbitan monoglyceride, lecithin, and lysolecithin.

[0091] Examples of preservatives, disinfectants, or antibacterial agents include polydronium chloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide or its hydrochloride, etc.), and Gloquil (manufactured by Rhodia).

[0092] Examples of pH adjusters include hydrochloric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, and phosphoric acid.

[0093] Examples of isotonic agents include sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, glycerin, and propylene glycol.

[0094] Examples of chelating agents include ascorbic acid, tetrasodium edetate, sodium edetate, and citric acid.

[0095] Examples of stabilizers include trometamol, sodium formaldehyde sulfoxylate (Rongalit), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, and glycerin monostearate.

[0096] Examples of antioxidants include water-soluble antioxidants such as ascorbic acid, ascorbic acid derivatives (calcium ascorbate, sodium ascorbate, potassium ascorbate, ascorbic acid phosphate, magnesium ascorbyl 2-phosphate, sodium ascorbyl phosphate, ascorbic acid 2-glucoside, etc.), sodium hydrogen sulfite, sodium sulfite, and sodium thiosulfate.

[0097] Examples of coloring agents include natural coloring agents such as gardenia yellow, matcha green color, cochineal color, gardenia yellow color, gardenia blue color, flavonoid color, caramel color, β-carotene, carotenoid color, paprika color, chlorophyll, and charcoal; and synthetic coloring agents such as Red No. 2, Red No. 3, Red No. 104, Red No. 105, Red No. 106, Yellow No. 4, Yellow No. 5, Blue No. 1, and titanium dioxide.

[0098] Examples of vitamins include vitamin B1 compounds such as thiamine hydrochloride, thiamine nitrate, and cocarboxylase (thiamine pyrophosphate); vitamin B1 derivatives such as fursultiamine, prosultiamine, octotiamine, thiamine disulfide, bisbentiamine, bisbutiamine, bisibutiamine, benfotiamine, dicethiamine, shikotiamine, and salts thereof; vitamin B6 compounds such as pyridoxine, pyridoxamine, pyridoxal, pyridoxine phosphate, pyridoxal phosphate, pyridoxamine phosphate, and salts thereof; and vitamin B12 compounds such as cobamacid, cyanocobalamin, hydroxocobalamin acetate, and mecobalamin. Furthermore, other vitamin B compounds include nicotinic acid and salts thereof, nicotinamide, pantothenic acid and salts thereof, panthenol, pantethine, folic acid and salts thereof, and biotin.

[0099] Examples of excipients include polysaccharides such as pullulan, carrageenan, xanthan gum, carboxymethylcellulose, cellulose, hemicellulose, gum arabic, guar gum, pectin, chitin, agarose, dextran, dextrin, isomaltodextrin, amylose, and starch including modified starch, or derivatives thereof; polymers such as proteins such as gelatin or casein; carbohydrates such as sorbitol, mannitol, maltitol, sucrose, maltose, lactose, α,α-trehalose, α,β-trehalose, gum arabic, corn starch, and crystalline cellulose; and inorganic substances such as aluminum hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, calcium sulfate, calcium sulfite, calcium carbonate, silica, calcium silicate, basic magnesium carbonate, kaolin, and talc.

[0100] The present invention will be explained in more detail by the following experiments, but the present invention is not limited to these experimental examples and can be appropriately modified or altered within the scope of the technical scope of the present invention.

[0101] Experiment 1: Confirmation of GLP-1 secretion-promoting effect of glycosylnaringenin and various aroma components. A composition containing 3′-α-monoglucosylnaringin was used as glycosylnaringenin to prepare compositions containing various aroma components, and the amount of GLP-1 secreted when the prepared compositions were allowed to act on human intestinal-derived cells was confirmed.

[0102] <Experiment 1-1: Preparation of 3″-α-monoglucosylnaringin-containing composition> Glycosyl naringenin was prepared according to the method described in Example 1 of Japanese Patent Application Laid-Open No. 2002-199896. Specifically, 50 g of naringin and 200 g of DE8 dextrin were dissolved in 500 mL of water with heating, adjusted to pH 7.0 with 2N aqueous sodium hydroxide, and 15 units of cyclodextrin glucanotransferase derived from Bacillus stearothermophilus (manufactured by Hayashibara Co., Ltd.) per 1 g of dextrin were added, followed by a reaction at 68°C for 48 hours. After completion of the reaction, the enzyme was inactivated by heating and then filtered to obtain a reaction solution containing α-glycosyl naringin. Next, the pH of this reaction solution was adjusted to 4.5, and 100 units of glucoamylase (trade name: Glucozyme (manufactured by Amano Enzyme Inc.)) per 1 g of dextrin were added, followed by a reaction at 55°C for 24 hours, thereby converting α-glycosyl naringin into α-glucosyl naringin. Naringin was produced. As disclosed in Japanese Patent Application Laid-Open No. 2002-199896, the produced α-glucosyl naringin contained 3"-α-monoglucosyl naringin and unreacted naringin, as well as other glycosides such as 3"-,4'-α-diglucosyl naringin and 4'-α-monoglucosyl naringin. Therefore, in order to increase the contents of 3"-α-monoglucosyl naringin and naringin in the composition, 1 mL of α-glucosidase (trade name: Transglucosidase L "Amano" (manufactured by Amano Enzyme Inc.)) was added per 1 g of α-glycosyl naringin, and the mixture was allowed to react at 55°C for 24 hours to decompose 3"-,4'-α-diglucosyl naringin and 4'-α-monoglucosyl naringin, thereby producing a composition containing 3"-α-monoglucosyl naringin and naringin. After the reaction was completed, the enzyme was inactivated by heating and the reaction solution was filtered. The resulting filtrate was passed through a column packed with a porous synthetic adsorbent at an SV (space velocity) of 2, thereby adsorbing 3'-α-monoglucosylnaringin and naringin in the solution onto the column. The column was then washed with water to remove glucose, salts, and other substances that did not adsorb onto the column.Next, 3"-α-monoglucosyl naringin and naringin were eluted by passing aqueous ethanol solutions with gradually increasing ethanol concentrations through the column. The eluate was concentrated under reduced pressure and powdered by spray drying to obtain a 3"-α-monoglucosyl naringin composition. HPLC analysis revealed that the composition (naringenin ratio (molar ratio)) was 70% 3"-α-monoglucosyl naringin and 30% naringin. The HPLC analysis was carried out under the following conditions:

[0103] <HPLC analysis conditions> Column: "CAPCELL PAK C18 UG 120" (Shiseido Co., Ltd.) Eluent: water / acetonitrile / acetic acid = 80 / 20 / 0.01 (v / v / v) Detection: UV 280 nm Temperature: 40°C Flow rate: 0.8 mL / min

[0104] <Experiment 1-2: Preparation of High-Purity 3"-α-Monoglucosyl Naringin> The 3"-α-monoglucosyl naringin composition obtained in Experiment 1-1 was dissolved in a water / acetonitrile / acetic acid mixture (80 / 20 / 0.01 (v / v / v)), and the solution was passed through a C18 column using a method similar to the HPLC analysis conditions described above, with an ultraviolet absorptiometer (UV 280 nm) as the detector, to separate 3"-α-monoglucosyl naringin and naringin, and the 3"-α-monoglucosyl naringin fraction was collected. The fraction was then concentrated under reduced pressure and powdered by spray drying to obtain a powdered, high-purity 3"-α-monoglucosyl naringin purified preparation. HPLC analysis revealed that the purity of 3"-α-monoglucosyl naringin in the obtained purified preparation was 99.0%.

[0105] <Experiment 1-3: Examination of the GLP-1 secretion promoting effect of combined use of mGN and aroma components> The GLP-1 secretion promoting effect was evaluated using NCI-H716 cells (human intestinal cell line; purchased from ATCC) by the following method.

[0106] [Test Substances] In Experiments 1-3, the following compounds were used as test substances. <Test Samples> A highly purified 3"-α-monoglucosylnaringin preparation (hereinafter referred to as mGN) obtained by the method of Experiment 1-2, and the following aroma components were used: citral, camphene (all manufactured by Sigma), citronellal (manufactured by Combi-blocks), methyl anthranilate, N-methylmethyl anthranilate, nootkatone (all manufactured by Tokyo Chemical Industry Co., Ltd.), α-pinene, β-pinene, β-ionone, β-caryophyllene, thymol (all manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), sabinene (manufactured by Toronto Research Chemicals), and valencene (manufactured by Cayman).

[0107] NCI-H716 cells were incubated at 37°C and 5% CO ２ After culturing, the cells were cultured in the presence of RPMI 1640 (containing 10% fetal bovine serum, manufactured by SIGMA) as a subculture medium. After culturing, 1.2 × 10 cells were plated on a 48-well plate coated with Matrigel (120 μL / well, manufactured by Corning). ５ The cells were suspended in DMEM (containing 10% fetal bovine serum and 4.5 mg / mL glucose, manufactured by Nissui Pharmaceutical Co., Ltd.) and added to a concentration of 10 cells / well. After culturing for 2 days, the cells were washed twice with 20 mM HEPES-containing HBSS buffer (Hank's Balanced Salt Solution). After removing the wash solution, the medium was replaced with 20 mM HEPES-HBSS (containing 0.01% BSA) containing the above-mentioned test sample and cultured for 2 hours. After culturing, diprotin-A (DPP4 inhibitor, manufactured by Abcam) and protease inhibitor (cComplete ＴＭThe supernatant was collected in a microcentrifuge tube containing EDTA-free protease inhibitor cocktail (Roche, catalog number: 1187358001). After centrifugation, the supernatant was stored at -80°C until use in GLP-1 measurement. GLP-1 in the medium was measured by ELISA using a GLP-1 Active Form Assay kit (IBL). The samples used for GLP-1 measurement were confirmed to be non-cytotoxic by measuring lactate dehydrogenase (LDH) activity in the cell supernatant. In this case, as a positive control for cytotoxicity, cells were added with 0.1% Triron X-100 / PBS(-) (Phosphate Buffered Saline), and the activity of LDH in the cell supernatant leaked from the cells in this case was set to 100%, and the ratio to the positive control (LDH activity in the cell supernatant of the sample / LDH activity of the positive control) was calculated as the cytotoxicity rate. Here, when the LDH activity was within ±2% of the cytotoxicity rate of the "control (cells cultured in 20 mM HEPES-HBSS containing no test sample instead of 20 mM HEPES-HBSS containing the test sample; "No addition" in Table 1)," it was determined that there was no cytotoxicity.

[0108] The amount of GLP-1 secretion was calculated as a relative value to the average amount of GLP-1 secretion obtained from the control (cells cultured in 20 mM HEPES-HBSS containing no test sample instead of 20 mM HEPES-HBSS containing the test sample; "No addition" in Table 1). Table 1 shows the amount of GLP-1 secretion measured when mGN and various aroma components were used alone, or when mGN and various aroma components were used in combination. As shown in Table 1, the concentrations of the test samples in the cell culture medium were 2.5 mM for mGN and 0.25 mM for various aroma components. The synergistic effect of mGN and various aroma components in promoting GLP-1 secretion was evaluated according to the following criteria.

[0109] [Formula] Synergistic effect: theoretical value < measured value Theoretical value = (A / D-1) x 100 + (B / D-1) x 100 Measured value = (C / D-1) x 100 A: GLP-1 secretion amount by adding mGN alone B: GLP-1 secretion amount by adding various aroma components C: GLP-1 secretion amount by using mGN in combination with various aroma components D: GLP-1 secretion amount in the control group (addition-free sample)

[0110] If the actual measured value was higher than the theoretical value based on the above formula, it was determined that there was a synergistic effect, and this was indicated by "O" in the table.

[0111]

[0112] As shown in Table 1, the combined use of mGN and specific aroma components was found to promote GLP-1 secretion compared to the control. That is, while mGN alone promoted GLP-1 secretion by approximately 1.6 times, the combined use of mGN and citral only promoted GLP-1 secretion by approximately 1.5 times. When citral was used alone, GLP-1 secretion was promoted by approximately 2.4 times, suggesting that the GLP-1 secretion-promoting effect of citral was suppressed by the combined use of mGN. Furthermore, when mGN and citronellal were used in combination, no synergistic increase in GLP-1 secretion was observed compared to when mGN or citronellal was used alone. In contrast, when mGN was used in combination with α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methyl methyl anthranilate, thymol, or nootkatone, higher GLP-1 secretion levels were confirmed than when mGN or each aroma component was used alone, and a synergistic effect was also determined. Among these, β-pinene, sabinene, methyl anthranilate, N-methyl methyl anthranilate, and thymol were not observed to promote GLP-1 secretion when used alone, but when used in combination with mGN, they were found to synergistically promote the GLP-1 secretion-promoting effect of mGN alone. Surprisingly, when mGN was used in combination with thymol, GLP-1 secretion levels were approximately 6.5-fold higher than the control, and approximately 4-fold higher than when used alone. On the other hand, the combined use of mGN and nootkatone also showed a GLP-1 secretion level that was approximately 10 times higher than the control and approximately 6 times higher than that of mGN alone.The above results demonstrate that when mGN is used in combination with α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, methyl N-methylanthranilate, thymol, or nootkatone, the GLP-1 secretion-promoting effect is synergistically enhanced, and particularly when mGN is used in combination with β-pinene, sabinene, methyl anthranilate, methyl N-methylanthranilate, thymol, or nootkatone, a more synergistic GLP-1 secretion-promoting effect is obtained, and in particular, when mGN is used in combination with thymol or nootkatone, a significantly superior GLP-1 secretion-promoting effect is obtained compared to when mGN is used in combination with other aroma components.

[0113] Experiment 2: Effect of the Composition Ratio of mGN and Thymol on GLP-1 Secretion Promotion 1> In Experiments 1-3, the GLP-1 secretion-promoting effect of the combined use of mGN and thymol, or mGN and nootkatone, which showed particularly excellent GLP-1 secretion-promoting effects, was investigated in more detail. Specifically, compositions were prepared in which mGN was mixed with 0.25 mM thymol at various molar ratios, and the effect on GLP-1 secretion was investigated. The experiment was conducted in the same manner as Experiments 1-3, except that the test samples shown in Table 2 were used, with an N number of 3.

[0114] The synergistic effect of mGN and thymol was judged to exist when the actual measured value was higher than the theoretical value based on the formula used in Experiments 1-3, and this was indicated by "◯" in the table. Furthermore, a Tukey-Kramer test was performed, and when there was a significant difference (significance rate p<0.05) between the control (D), mGN alone (A), and thymol alone (B) in the GLP-1 secretion levels of A to D, the combined use of mGN and thymol (C) was indicated by "◎" in the table.

[0115]

[0116] As shown in Table 2, thymol alone at a concentration of 0.25 mM did not exhibit any GLP-1 secretion-promoting effect; in fact, in most cases, GLP-1 secretion was reduced compared to the control. On the other hand, when mGN was added at concentrations of 0.025 mM to 150 mM, GLP-1 secretion was promoted to a certain extent in an mGN concentration-dependent manner, even when mGN was used alone. In contrast, the combined use of thymol and mGN significantly promoted GLP-1 secretion compared to the use of either compound alone. That is, a synergistic effect was observed when mGN and thymol were used in combination in all of Tests 2-1 to 2-6, where the molar ratio of mGN to thymol was in the range of 600:1 to 1:10. In particular, Tests 2-2 to 2-5, where the molar ratio of mGN to thymol was in the range of 200:1 to 1:1, demonstrated a more effective enhancement of GLP-1 secretion.

[0117] <Experiment 3: Effect of the composition ratio of mGN to thymol on promoting GLP-1 secretion 2> Next, based on the results shown in Table 2, Test No. 2-4 had the highest GLP-1 secretion promoting effect, and compositions were prepared by mixing 25 mM mGN with thymol at various molar ratios, and the effect on GLP-1 secretion was examined. The experiment was conducted in the same manner as Experiments 1-3, except that the test samples shown in Table 3 were used, and the N number was 3. The synergistic effect was evaluated in the same manner as in Experiment 2. The evaluation results are shown in Table 3.

[0118]

[0119] As shown in Table 3, thymol alone did not exhibit any GLP-1 secretion-promoting effect at concentrations ranging from 0.0067 mM to 0.125 mM; in fact, GLP-1 secretion was reduced compared to the control. In contrast, when thymol was administered concomitantly with mGN at concentrations ranging from 0.0067 mM to 0.125 mM, GLP-1 secretion was surprisingly significantly promoted, and the secretion was greater than when mGN was administered alone. As shown in Table 3, a synergistic effect was observed in all of Tests 3-1 to 3-3, in which the molar ratio of mGN to thymol was in the range of 3731:1 to 200:1. A particularly significant synergistic effect was observed in Test 3-1, in which the molar ratio of mGN to thymol was 200:1. Considering the results of Experiments 2 and 3, when the composition of the present invention contains glycosylnaringenin and thymol, there are no particular limitations on the ratio of glycosylnaringenin to thymol, but from the viewpoint of obtaining a synergistic GLP-1 secretion-promoting effect, it is determined that the glycosylnaringenin and thymol are contained in a molar ratio of 4000:1 to 1:10, more preferably 3731:1 to 1:10, and even more preferably 200:1 to 1:1. Furthermore, in Samples 2-2, 2-3, and 2-4, the degree of synergistic effect was particularly large, and therefore it was determined that the glycosylnaringenin and thymol are contained in a molar ratio of 100:1 to 1:1.

[0120] Experiment 4: Effect of the Composition Ratio of mGN and Nootkatone on GLP-1 Secretion Promotion Next, among the GLP-1 secretion-promoting effects of the combined use of mGN and thymol or mGN and nootkatone, which showed particularly excellent GLP-1 secretion-promoting effects in Experiments 1-3, the GLP-1 secretion-promoting effect of the combined use of mGN and nootkatone was further investigated in detail. That is, compositions were prepared by mixing mGN and nootkatone at various molar ratios, and the effect on GLP-1 secretion was investigated. The experiment was conducted in the same manner as Experiments 1-3, except that the test samples shown in Table 4 were used, and the N number was 3. The synergistic effect was evaluated in the same manner as in Experiment 2. The evaluation results are shown in Table 4.

[0121]

[0122] As shown in Table 4, even when nootkatone was used alone, GLP-1 secretion was promoted in a concentration-dependent manner, but when nootkatone was used in combination with mGN, GLP-1 secretion was promoted even more significantly. Specifically, a synergistic effect was observed in all of Tests No. 4-1 to 4-6, in which the molar ratio of mGN to nootkatone was in the range of 1000:1 to 1:5. In particular, it was revealed that Samples No. 4-2 to 4-3, which contained mGN and nootkatone in a molar ratio of 10:1 to 1:1, exhibited a more effective enhancement of the GLP-1 secretion-promoting effect. From these results, it was determined that when the composition of the present invention contains glycosylnaringenin and nootkatone, the molar ratio of glycosylnaringenin to nootkatone is preferably 1000:1 to 1:5, and more preferably 10:1 to 1:1, from the perspective of achieving a synergistic GLP-1 secretion-promoting effect.

[0123] Experiment 5: Effect of the Composition Ratio of mGN to a 1:1 Mixture of Thymol and Nootkatone on Promoting GLP-1 Secretion In order to examine the combined effect of the three components of mGN, thymol, and nootkatone, compositions were prepared in various molar ratios of a 1:1 mixture of mGN, thymol, and nootkatone (hereinafter referred to as a "1:1 mixture of thymol and nootkatone"), and the effect on GLP-1 secretion was examined. The experiment was conducted in the same manner as Experiments 1-3, except that the test samples shown in Table 5 were used, and the N number was 3. The synergistic effect was evaluated in the same manner as in Experiment 2. The evaluation results are shown in Table 5. In Table 5, the molar concentration of the 1:1 mixture of thymol and nootkatone is the sum of the molar concentrations of thymol and nootkatone contained in the mixture, and the molar ratio of mGN to the mixture was calculated based on this sum.

[0124]

[0125] As shown in Table 5, when a 1:1 mixture of thymol and nootkatone (a 1:1 molar ratio) was used alone, the amount of GLP-1 secretion was almost the same as that in the control group at concentrations ranging from 0.025 mM to 0.042 mM, and no GLP-1 secretion-promoting effect was observed. In contrast, when a 1:1 mixture of thymol and nootkatone (0.025 mM to 0.042 mM) was used in combination with mGN, GLP-1 secretion was significantly promoted compared to the 1:1 mixture of thymol and nootkatone or mGN used alone. Furthermore, when a 1:1 mixture of thymol and nootkatone was used at 0.25 mM, a GLP-1 secretion-promoting effect was observed compared to the control group. Surprisingly, GLP-1 secretion was significantly promoted with the addition of only a small amount of mGN (0.025 mM). As shown in Table 5, a synergistic effect was observed in all of Tests No. 5-1 to 5-3, in which the molar ratio of mGN to a 1:1 mixture of thymol and nootkatone was in the range of 1000:1 to 1:10, and the synergistic effect was particularly pronounced in Test No. 5-1, which contained mGN and thymol at a molar ratio of 1:10.

[0126] Experiment 6: Effect of the composition ratio of mGN to a 1:2 mixture of thymol and nootkatone on promoting GLP-1 secretion Compositions were prepared by mixing mGN with thymol and nootkatone at a molar ratio of 1:2 (hereinafter referred to as "1:2 mixture of thymol and nootkatone") at various molar ratios, and the effect on GLP-1 secretion was examined. The experiment was carried out in the same manner as Experiments 1-3, except that the test samples shown in Table 6 were used, and the N number was 3. The synergistic effect was evaluated in the same manner as in Experiment 2. The evaluation results are shown in Table 6.

[0127]

[0128] As shown in Table 6, when a 1:2 mixture of thymol and nootkatone, in which thymol and nootkatone were mixed at a molar ratio of 1:2, was used at 0.25 mM, a GLP-1 secretion promoting effect was observed compared to the control without addition, and when used in combination with mGN, GLP-1 secretion was further promoted. Furthermore, when the 1:2 mixture of thymol and nootkatone was used alone, no GLP-1 secretion promoting effect was observed in the concentration range of 0.025 mM to 0.042 mM. However, when the 1:2 mixture of thymol and nootkatone was used in combination with mGN at a concentration of 0.025 mM to 0.042 mM, surprisingly, GLP-1 secretion was significantly promoted. As shown in Table 6, Test No. 1, in which the molar ratio of mGN to the 1:2 mixture of thymol and nootkatone was in the range of 1000:1 to 1:10, showed a significant GLP-1 secretion promoting effect. In all of Experiments 6-1 to 6-3, a synergistic effect was observed when mGN was used in combination with a 1:2 mixture of thymol and nootkatone, and the synergistic effect was particularly pronounced in Experiments 6-2 and 6-3, which contained mGN and a 1:2 mixture of thymol and nootkatone at a molar ratio of 1000:1 to 600:1. Considering the results of Experiments 5 and 6, when the composition of the present invention contains glycosylnaringenin, thymol, and nootkatone, there are no particular limitations on the blending ratio of thymol and nootkatone, but from the perspective of obtaining a synergistic GLP-1 secretion-promoting effect, it was determined that the glycosylnaringenin and thymol and nootkatone mixture should preferably be contained in a molar ratio of 1000:1 to 1:10.

[0129] The present invention will be specifically described below based on examples, but the present invention is not limited to these examples.

[0130] <Lemon-flavored beverage> 0.015 parts by mass of the 3"-α-monoglucosyl naringin composition obtained in Experiment 1-1, 30 parts by mass of reduced starch syrup, 30 parts by mass of granulated sugar, 3 parts by mass of honey, 0.07 parts by mass of acesulfame potassium, 0.03 parts by mass of sucralose, 0.3 parts by mass of vitamin C, 3 parts by mass of citric acid, 1 part by mass of sodium citrate, 1 part by mass of lemon flavoring, 1 part by mass of yuzu flavoring, and 0.00003 parts by mass of thymol 0.001 parts by mass of nootkatone was added, and after thorough stirring, water was added to make a total of 1,000 parts by mass. The mixture was then sterilized at 90°C for 30 seconds. The resulting lemon-flavored beverage had a sharp sweet aftertaste, a fresh topping, and a slightly bitter peel-like texture. Furthermore, when the resulting lemon-flavored beverage was stored at 40°C for 4 weeks, the lemon aroma was well maintained and the generation of undesirable deterioration odors was suppressed. This product can be advantageously used as a beverage for promoting GLP-1 secretion and suppressing blood glucose elevation.

[0131] <Carbonated Beverage> 20 parts by mass of high-fructose liquid sugar, 0.1 part by mass of acesulfame potassium, 0.02 part by mass of sucralose, 2 parts by mass of citric acid, 0.5 part by mass of sodium citrate, and 0.015 part by mass of the 3"-α-monoglucosyl naringin composition obtained in Experiment 1-1 were mixed with 197 parts by mass of water and stirred well until dissolved. An appropriate amount of lemon flavor, 0.0001 part by mass of thymol, and 0.0001 part by mass of nootkatone were added thereto and stirred well. After that, 750 parts by mass of carbonated water was added to obtain a carbonated beverage. The obtained carbonated beverage had a moderate bitterness, a crisp sweet aftertaste, a refreshing taste, and maintained a good lemon flavor. This product can be advantageously used as a beverage for promoting GLP-1 secretion and suppressing blood glucose elevation.

[0132] <Fruit Juice Beverage> A fruit juice beverage was prepared by mixing 100 parts by mass of high-fructose corn syrup, 22 parts by mass of concentrated orange juice (1 / 5 concentrated fruit juice), 8 parts by mass of citric acid, 1 part by mass of vitamin C, 0.04 part by mass of stevia, 0.03 part by mass of the 3"-α-monoglucosyl naringin composition obtained in Experiment 1-1, 1 part by mass of orange flavoring, 0.002 part by mass of nootkatone, and 0.00001 part by mass of thymol, and adding water to make a total of 1000 parts by mass. The obtained fruit juice beverage had an enhanced orange juice flavor, and the inclusion of nootkatone and thymol further enhanced the fruit-derived fruit juice flavor, resulting in a pleasant aroma and a grapefruit-like flavor and bitterness, making it a desirable beverage. Furthermore, the aftertaste due to the addition of a high-intensity sweetener was suppressed, resulting in a refreshing fruit juice beverage. This product can be advantageously used as a beverage for promoting GLP-1 secretion and suppressing blood sugar elevation.

[0133] <Chu-hai> 0.05 parts by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 0.1 parts by mass of acesulfame potassium, 0.02 parts by mass of sucralose, 4 parts by mass of citric acid, and 1 part by mass of sodium citrate were mixed with 133 parts by mass of 50% alcohol (v / v) vodka (Nikka Whisky Company, Wilkinson Vodka 50°) and stirred well until dissolved. An appropriate amount of lemon flavoring, 0.0001 parts by mass of thymol, and 0.0001 parts by mass of nootkatone were added thereto and stirred well. Carbonated water was added to make a total of 1,000 parts by mass to obtain a chu-hai. The obtained chu-hai had an alcohol content of 6%, but the alcohol taste was enhanced, and it had a fresh lemon flavor and a clean sweetness without any unpleasant flavors, making it easy to drink.

[0134] <Beer-Taste Beverage> 0.05 parts by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 2 parts by mass of α,α-trehalose, 2 parts by mass of malt extract, 0.02 parts by mass of hop extract (as iso-α acid), 0.00005 parts by mass of thymol, and 0.001 parts by mass of nootkatone were dissolved in purified water to make a total of 1000 parts by mass. The mixture was then boiled for 1 hour, cooled, and replenished with water to replace the evaporated amount. An appropriate amount of beer flavor was added, and the mixture was subjected to a clarification process by filtration through diatomaceous earth and filtration through a filter. The resulting beer-taste beverage was excellent in terms of color, flavor, body, crisp bitterness, and smoothness.

[0135] <Tea Beverage> 800 g of deionized water at 70°C was added to 25 g of green tea leaves, and the tea components were extracted for 6 minutes. The tea leaf residue was then removed by filtration to obtain 700 ml of extract. The obtained extract was diluted 3-fold with deionized water, and L-ascorbic acid was added to 50 ppm. The pH was adjusted to 6.2 with sodium bicarbonate. Next, the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1 was added to 10 ppm and thymol to 0.003 ppm. The mixture was then dispensed in 350 ml portions into heat-resistant glass containers, sealed, and sterilized at 121°C for 10 minutes to obtain a tea beverage. The resulting green tea beverage had a moderate bitterness and an excellent tea aroma. This product can be advantageously used as a beverage for promoting GLP-1 secretion and suppressing blood glucose elevation.

[0136] <Black tea beverage> Black tea leaves were extracted with hot water in a conventional manner to obtain a black tea extract. 320 parts by mass of this extract, 70 parts by mass of sugar, 0.015 parts by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 0.1 parts by mass of bergamot flavoring, 0.00002 parts by mass of thymol, and 0.00026 parts by mass of nootkatone were mixed together and then diluted with deionized water. The pH was adjusted to 5.8 with sodium bicarbonate to prepare a total of 1,000 parts by mass of a black tea beverage. This was filled into 350 ml cans and then retort sterilized (120°C, 4 minutes). The obtained black tea beverage had a moderate bitterness and astringency, and had a black tea flavor and a fruity taste. This product can be advantageously used as a beverage for promoting GLP-1 secretion and suppressing blood glucose elevation.

[0137] <Coffee> 100 parts by mass of Arabica coffee beans roasted to an L value (brightness of coffee beans measured with a colorimeter) of 22 were ground and extracted with hot water. 200 parts by mass of water, 10 ppm of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 0.011 ppm of thymol, and 0.14 ppm of nootkatone were added to 500 parts by mass of a coffee extract prepared by adjusting the coffee bean extract to a Brix of 2. The pH was adjusted, and the resulting mixture was packed into cans and sterilized by retort to obtain canned coffee. The resulting canned coffee was easy to drink, with a harmonious balance of the bitterness of coffee and reduced off-flavors and odors. This product can be advantageously used as a beverage for promoting GLP-1 secretion and suppressing blood glucose elevation.

[0138] <Jelly> 200 parts by mass of sugar, 2.5 parts by mass of κ-carrageenan, 2.5 parts by mass of lost bean gum, 2.5 parts by mass of sodium citrate, 1 part by mass of potassium chloride, and 0.2 parts by mass of acesulfame potassium were thoroughly mixed and added to a pot containing 650 parts by mass of water, taking care not to form lumps. To this was added 0.01 parts by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, and the mixture was boiled down and the water evaporated to a mass of 800 parts by mass. The mixture was then cooled to approximately 70°C, and 35 parts by mass of concentrated orange juice (1 / 5 concentrated juice), an appropriate amount of orange flavoring, 0.00003 parts by mass of thymol, and 0.001 parts by mass of nootkatone were added, and the pH was adjusted to fall within the range of 3.2 to 4.0 using a 50% aqueous citric acid solution. This solution was filled into a jelly cup and left to solidify in a refrigerator, yielding orange jelly. The resulting orange jelly had an enhanced orange juice flavor and freshness, and was less prone to the unpleasant taste of sweeteners. This product can be advantageously used as a food for promoting GLP-1 secretion and suppressing blood sugar elevation.

[0139] <Ice Dessert> 30 parts by mass of sugar, 20 parts by mass of α,α-trehalose, 0.1 part by mass of grapefruit flavoring, 0.015 part by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 0.000005 part by mass of thymol, and 0.001 part by mass of nootkatone were completely dissolved in 300 parts by mass of grapefruit juice and 350 parts by mass of water, and the mixture was stirred while frozen in a sorbeteur (sherbet maker) to produce grapefruit-flavored sherbet, which was then filled into plastic cups and stored in a freezer at -20°C. A control ice dessert was prepared in the same manner as above except that the 3"-α-monoglucosyl naringin composition was not added. The ice dessert of the present invention had a low solids content and sugar content, and therefore had a refreshing, low sweetness, an enhanced grapefruit juice flavor, and a good flavor compared to the control.

[0140] <Gummy Candy> 170 parts by mass of sugar, 250 parts by mass of maltose syrup (trade name "Maltrap", manufactured by Hayashibara Co., Ltd.), 24 parts by mass of gelatin, 0.1 part by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 48 parts by mass of water, 12 parts by mass of 50% by mass aqueous citric acid solution, 0.6 part by mass of grapefruit flavoring, appropriate amounts of coloring agent, 0.0001 part by mass of thymol, and 0.0001 part by mass of nootkatone were mixed according to a conventional method. The mixture was poured into a starch mold, dried for one day, and then molded to obtain gummies. Because the composition of the present invention has excellent water solubility, the obtained gummies were transparent and had a slight bitterness, highlighting the freshness of grapefruit.

[0141] <Hard Candy> 240 parts by mass of high-fructose liquid sugar, 220 parts by mass of maltose starch syrup (trade name "Maltrap", manufactured by Hayashibara Co., Ltd.), and 80 parts by mass of water were mixed and boiled down to 150°C. The mixture was once cooled to below 120°C, and 0.01 part by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 0.8 parts by mass of peppermint oil, 1.1 parts by mass of menthol, 0.005 parts by mass of thymol, 0.00025 parts by mass of nootkatone, and an appropriate amount of coloring agent were added, and the mixture was molded to produce a candy. The obtained hard candy had an enhanced mint flavor and a refreshing feeling. Furthermore, since it contains the 3"-α-monoglucosyl naringin composition and thymol, it has effects of relieving roughness, inflammation, and pain in the oral cavity and throat, as well as antibacterial effects, and is a hard candy that can be used for the purpose of maintaining and improving oral health.

[0142] <Nutritional Drink> An amino acid mixture was prepared containing 4 parts by mass of isoleucine, 6 parts by mass of leucine, 8 parts by mass of lysine, 8 parts by mass of phenylalanine, 1 part by mass of tyrosine, 12 parts by mass of tryptophan, 8 parts by mass of valine, 1 part by mass of aspartic acid, 1 part by mass of serine, 8 parts by mass of aminoacetic acid, 8 parts by mass of alanine, 2 parts by mass of histidine, 8 parts by mass of arginine, 2 parts by mass of threonine, and 1 part by mass of methionine, and dissolved in water to prepare a 2% solution of the mixture. To 50 parts by mass of this solution were added 0.5 parts by mass of ascorbic acid, 0.01 parts by mass of nicotinamide, 0.01 parts by mass of vitamin B1, 0.01 parts by mass of vitamin B2, 0.01 parts by mass of vitamin B6, 1.8 parts by mass of concentrated grapefruit juice (1 / 5 concentrated grapefruit juice), 0.01 parts by mass of the 3"-α-monoglucosylnaringin composition prepared in Experiment 1-1, 0.0003 parts by mass of thymol, and 0.003 parts by mass of nootkatone, and water was added to make a nutritional drink with a total of 100 parts by mass. This product is suitable for promoting GLP-1 secretion and suppressing blood glucose elevation, and is a tasty nutritional drink that does not brown or develop an unpleasant odor even when stored for a long period of time, has a reduced unpleasant taste of the amino acids themselves, and has improved palatability.

[0143] <Capsules> 10 parts by mass of calcium acetate monohydrate, 50 parts by mass of magnesium L-lactate trihydrate, 60 parts by mass of maltose, 30 parts by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 0.1 part by mass of thymol, and 0.06 part by mass of nootkatone were uniformly mixed and passed through a granulator to form granules, which were then encapsulated in gelatin capsules according to standard methods to produce a capsule supplement containing 150 mg per capsule. This product is suitable as an oral intake for promoting GLP-1 secretion, suppressing blood sugar elevation, and promoting health.

[0144] <Tablets> Following a conventional method, 5 parts by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 68 parts by mass of maltose, 15 parts by mass of α,α-trehalose, 5 parts by mass of pullulan-containing powder, 0.12 parts by mass of thymol, and 0.1 parts by mass of grapefruit flavor were uniformly mixed, and the mixture was compressed into tablets (200 mg / tablet). This product has appropriate strength and a good flavor and taste, and is suitable as a tablet for promoting GLP-1 secretion and suppressing blood glucose elevation. In addition, since it contains thymol, it is also suitable as an oral intake for improving and maintaining blood flow and for promoting health, such as preventing or improving sensitivity to cold.

[0145] <Water-Soluble Flavor> Lemon oil and 65 wt% aqueous ethanol were mixed, stirred, and then left at low temperature. The mixture was separated into an aqueous layer (essence layer) containing water-soluble aroma components in the aqueous ethanol and an oil phase containing water-insoluble components, and the aqueous layer was extracted to obtain lemon essence. 2 parts by mass of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1, 0.01 part by mass of thymol, and 0.05 part by mass of nootkatone were mixed with 98 parts by mass of the obtained lemon essence to obtain a water-soluble lemon flavor. The obtained lemon flavor exhibited reduced deterioration odor due to long-term storage and retained a good flavor and aroma. Furthermore, because the composition of the present invention has excellent water solubility, it can be used as a highly stable water-soluble liquid flavor. This product can be added to ordinary foods and beverages in an amount of 0.01 to 1% to enhance the expression and persistence of flavor. Furthermore, it can be used as an oral intake for promoting GLP-1 secretion, suppressing blood sugar elevation, and promoting health.

[0146] <Powdered Flavoring> 5 g of sucrose fatty acid ester with an HLB of 15 and 2 g of the 3"-α-monoglucosyl naringin composition prepared in Experiment 1-1 were dissolved in 100 g of water and sterilized by heating at 85-90°C for 15 minutes. This solution was cooled to approximately 40°C and then mixed with 10 g of lemon oil, 0.001 g of thymol, and 0.5 g of nootkatone while stirring with a homomixer to obtain an emulsified flavoring. This product can be easily made into a powdered flavoring by further drying by a method such as spray drying. All of the obtained powdered flavorings retained a good aroma and flavor without developing a deteriorated odor due to long-term storage. When added to ordinary foods and beverages in an amount of 0.1-3%, this product can be used as an oral intake for promoting GLP-1 secretion, suppressing blood sugar elevation, and promoting health.

[0147] As described above, the composition of the present invention has an effective GLP-1 secretion-promoting effect and is therefore useful for preventing or ameliorating obesity, diabetes, and postprandial hyperglycemia, which are conditions in which promotion of GLP-1 secretion is effective, suppressing blood glucose elevation, suppressing glucagon secretion, suppressing gastric excretion and gastric acid secretion, and regulating appetite, and can be provided in the form of a food, supplement, pharmaceutical, quasi-drug, fragrance, or the like.

Claims

1. A composition for promoting GLP-1 secretion, comprising component (A) glycosylnaringenin and component (B) at least one active ingredient selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methyl methyl anthranilate, thymol, and nootkatone.

2. 2. The composition for promoting GLP-1 secretion according to claim 1, wherein the component (A) is 3″-α-monoglucosylnaringin.

3. 3. The composition for promoting GLP-1 secretion according to claim 1, wherein the component (B) is thymol and / or nootkatone.

4. 4. The composition for promoting GLP-1 secretion according to claim 1, comprising the component (A) and the component (B) in a molar ratio of 10,000:1 to 1:

10.

5. The composition for promoting GLP-1 secretion according to any one of claims 1 to 4, comprising 0.0001% by mass or more of the component (A).

6. The composition for promoting GLP-1 secretion according to any one of claims 1 to 5, which is used for at least one effect selected from the group consisting of prevention or amelioration of obesity, diabetes, and postprandial hyperglycemia, suppression of blood glucose increase, suppression of glucagon secretion, suppression of gastric excretion and gastric acid secretion, appetite suppression, food intake suppression, and satiety induction.

7. A composition comprising component (A) glycosylnaringenin and component (B) at least one member selected from the group consisting of α-pinene, β-pinene, sabinene, camphene, valencene, β-caryophyllene, β-ionone, methyl anthranilate, N-methyl methyl anthranilate, thymol, and nootkatone.

8. The composition according to claim 7, wherein the molar ratio of said component (A) to said component (B) is in the range of 10,000:1 to 1:

10.

9. The composition according to claim 7 or 8, wherein the component (A) is 3"-α-monoglucosyl naringin.

10. 10. The composition according to claim 7, wherein component (B) is thymol and / or nootkatone.

11. The composition according to claim 7 , comprising 0.0001% by mass or more of the component (A).

12. A food or drink, a supplement, a flavoring, a medicine or quasi-drug, or a feed comprising the composition according to any one of claims 1 to 11.

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