Vascular endothelial function improving agent

Abstract

The technical problem to be solved by the present invention is to provide an excellent vascular endothelial function improving agent containing hesperidin and rutin. The present invention comprises a vascular endothelial function improving agent, which contains alpha-glucosyl hesperidin and alpha-glucosyl rutin.

Description

TECHNICAL FIELD

[0001] The present application relates to a vascular endothelial function improver. BACKGROUND

[0002] Vascular endothelial cells are cells of the innermost layer of blood vessels throughout the body and play an important role in maintaining the healthy state of blood vessels. It is known that the function of vascular endothelial cells, i.e., vascular endothelial function, decreases with the disturbance of life habits such as smoking, drinking, diet, exercise, overwork, stress, and age increase. The evaluation of vascular endothelial function can be performed by FMD (Flow Mediated Dilation) examination. In general, the evaluation of FMD value of 7% or more is normal, 4% or more and less than 7% is a borderline range, and less than 4% is suspected of abnormal vascular endothelial function. If the vascular endothelial function is impaired, the vascular wall thickens and hardens.

[0003] Thus, researches for improving blood circulation using vitamin P are being conducted. For example, Patent Literature 1 discloses a blood circulation improver containing a prescribed amount of glycosylated vitamin P and trehalose. Patent Literature 2 discloses an elastase activity inhibitor containing vitamin P. PRIOR ART DOCUMENTS PATENT LITERATURE

[0004] Patent Literature 1: Japanese Patent No. 4295840 Patent Literature 2: International Publication No. 2009 / 116450 SUMMARY PROBLEMS TO BE SOLVED BY THE INVENTION

[0005] In Patent Literature 1, glycosylated hesperidin is used as glycosylated vitamin P, and a paste containing the glycosylated hesperidin and crystalline trehalose five times or more than the glycosylated hesperidin is used for muscle stiffness relaxation evaluation, and as a result, it is shown that the blood circulation improving effect of glycosylated vitamin P is promoted with trehalose. In addition, in Patent Literature 2, the blood circulation promoting effect of glycosylated naringin, glycosylated hesperidin, or glycosylated rutin without trehalose is studied.

[0006] However, the research and effect of vitamin P on vascular endothelial function are not sufficient in the above-described literatures, and there is room for improvement.

[0007] The present application relates to a vascular endothelial function improver. MEANS OF SOLVING THE PROBLEMS

[0008] The present inventors have conducted intensive studies in order to solve the above-described technical problems. As a result, they have found that the above-described technical problems can be solved by having the following configuration, thereby completing the present application. The present application is a form relating to, for example, [1] to [4] described below. [1] A vascular endothelial function improver containing α-glucosyl hesperidin and α-glucosyl rutin. [2] The vascular endothelial function improver described in [1], containing α-mono-glucosyl hesperidin and α-mono-glucosyl rutin. [3] The vascular endothelial function improver described in [2], wherein the content of α-mono-glucosyl rutin is 20 to 500 parts by mass relative to 100 parts by mass of α-mono-glucosyl hesperidin. [4] A food containing the vascular endothelial function improver described in any one of [1] to [3]. Effects of the Invention

[0009] According to the present application, an excellent vascular endothelial function improver containing hesperidin and rutin can be provided.

[0010] Further, according to the present application, the flexibility of blood vessels, which decreases as age increases, can be maintained. BRIEF DESCRIPTION OF DRAWINGS

[0011] Figure 1 is a graph showing the amount of change (%) in FMD value resulting from continuous intake of αG hesperidin PA-T and αG rutin PS for 4 weeks. Figure 1 (A) and the rate of change (%) ( Figure 1 (B). Figure 2 is a graph showing the amount of change in FMD value (%) resulting from continuous intake of αG hesperidin PA-T and αG rutin PS for 8 weeks. DETAILED DESCRIPTION

[0012] Hereinafter, preferred modes for carrying out the present application will be described. The embodiments described below show one example of representative embodiments of the present application, and do not thereby limit the scope of the present application. In addition, unless otherwise specifically stated, the notation of "A to B" with respect to a numerical range means A or more and B or less. For example, the notation of "1 to 5%" means 1% or more and 5% or less.

[0013] One embodiment of the present application is a vascular endothelial function improver containing α-glucosyl hesperidin and α-glucosyl rutin.

[0014] <α-glucosyl hesperidin> The α-glucosyl hesperidin (also referred to as α-glucosyl hesperidin) is a general term for compounds in which one or more glucose molecules are added to the hydroxyl group of the rhamnose unit of hesperidin via an α-1,4 bond. The α-glucosyl hesperidin in the present application can be composed of one of the compounds having such a structure alone, or a mixture of two or more. In addition, hesperidin is a compound in which β-rutinosyl (6-O-α-L-rhamnopyranosyl-β-D-glucopyranose) is bonded to the hydroxyl group at the 7-position of hesperetin, i.e., a hesperetin glycoside.

[0015] The α-glucosyl hesperidin can be represented by the following formula (1). In formula (1), n is an integer of 0 or 1 or more, for example, an integer of 1 to 19.

[0016] [Chemical Formula 1]

[0017] The α-glucosyl hesperidin is a compound included as a main component in a raw material called "enzyme-treated hesperidin" (sometimes referred to as "glycosylated hesperidin"). In the α-glucosyl hesperidin, a compound in which only one glucose is bonded is referred to as "α-monoglucosyl hesperidin", and a compound in which two or more glucoses are bonded is referred to as "α-multiglucosyl hesperidin". That is, in formula (1), the α-monoglucosyl hesperidin is a compound in which n is 0, and the α-multiglucosyl hesperidin is generally a compound in which n is an integer of 1 to 19.

[0018] The enzyme-treated hesperidin is an aggregate of compounds generated by enzyme treatment in relation to the sugar of hesperidin, and generally contains a mixture of compounds in which the number of glucoses bonded to hesperidin differs, for example, a mixture composed of α-monoglucosyl hesperidin and α-multiglucosyl hesperidin. In addition, in addition to the α-glucosyl hesperidin, unreacted hesperidin and α-glucosyl hesperidin other than hesperidin derivatives (also referred to as other hesperidin derivatives) such as 7-glucosyl hesperetin can be contained. However, the enzyme-treated hesperidin preferably does not contain hesperetin.

[0019] As an example of the above-described enzyme treatment in relation to the sugar of hesperidin, the following is described. [1] Hesperidin is allowed to act on a sugar donor such as an α-glucosyl sugar compound (e.g., a cyclodextrin, a starch partial degradation product) in the presence of a sugar glycosyltransferase, and glucose is added to the glucose unit of hesperidin via an α-1,4 bond to generate α-glucosyl hesperidin, and a composition containing unreacted hesperidin and α-glucosyl hesperidin (first enzyme-treated hesperidin) is obtained. [2] The α-glucosyl hesperidin generated in the above [1] is allowed to react with a glucosidase or the like, and other glucoses are cleaved from the glucose chain bonded to the glucose unit of hesperidin, leaving only one molecule, thereby generating α-mono-glucosyl hesperidin, and a composition containing the hesperidin remaining in an unreacted state and the α-mono-glucosyl hesperidin is obtained (second enzyme-treated hesperidin). [3] The hesperidin remaining in an unreacted state in the above [2] is allowed to react with an α-L-rhamnosidase, and rhamnose contained in the rhamnose unit of the rutin is cleaved, thereby generating 7-glucosyl naringenin, and a composition containing the 7-glucosyl naringenin and the α-mono-glucosyl hesperidin is obtained (third enzyme-treated hesperidin).

[0020] As an example of the first enzyme treatment, a glycosyltransferase (e.g., cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19) or the like having a function of adding glucose to hesperidin) can be exemplified, which is allowed to react with hesperidin in the presence of an α-glucosyl sugar compound (e.g., cyclodextrin, starch partial degradation product).

[0021] In the vascular endothelial function improver of the embodiment of the present application, a composition containing α-glucosyl hesperidin, i.e., enzyme-treated hesperidin, is preferably used in view of the effects of the present application or the like, and any one of the first enzyme-treated hesperidin, the second enzyme-treated hesperidin, and the third enzyme-treated hesperidin can be used.

[0022] In view of the effects of the present application or the like, the enzyme-treated hesperidin preferably contains at least α-glucosyl hesperidin, and further contains a mixture of one or both of hesperidin and 7-glucosyl naringenin.

[0023] As a commercially available product of the enzyme-treated hesperidin, for example, "αG Hesperidin PS-CC" and "αG Hesperidin PA-T" of Toyo Sugar Refining Co., Ltd. can be exemplified. "αG Hesperidin PS-CC" contains 80% by mass or more of α-mono-glucosyl hesperidin, and contains 7-glucosyl naringenin. "αG Hesperidin PA-T" contains 75% by mass or more of α-mono-glucosyl hesperidin, and contains hesperidin.

[0024] As the α-glucosyl hesperidin, α-mono-glucosyl hesperidin is preferable. This is because the molecular weight of α-mono-glucosyl hesperidin is smaller than that of α-poly-glucosyl hesperidin, and thus the number of molecules per unit mass of α-mono-glucosyl hesperidin is larger, which is advantageous in terms of the effect.

[0025] The α-monoglucosyl hesperidin can be produced by subjecting the α- polyglucosyl hesperidin to a sugar-hydrolyzing enzyme to cleave the glucose bonded to the hesperidin and leave only one (second enzyme treatment of hesperidin). As the sugar-hydrolyzing enzyme, an enzyme having glucoamylase activity to cleave an α-1,4-glucoside bond at a glucose unit, for example, glucoamylase (EC 3.2.1.3) can be exemplified. The proportion of the α-monoglucosyl hesperidin in the α-glucosyl hesperidin can be adjusted by the temperature, time conditions, etc. of the enzyme treatment based on the glucoamylase, and furthermore, a method of purifying and separating the α-monoglucosyl hesperidin from the mixture of the enzyme-treated hesperidin is also known.

[0026] The presence of the various α-glucosyl hesperidin, hesperidin and other components contained in the enzyme-treated hesperidin can be confirmed by HPLC chromatography, and the content of each component or the purity of a desired specific component can be calculated from the peak area of the chromatography.

[0027] The method of producing the α-glucosyl hesperidin is not particularly limited, and a known method can be used. It is preferable to produce by the enzyme treatment of hesperidin described above because the yield is good and the production is easy. The method of obtaining and preparing the hesperidin is not particularly limited, and a compound generally produced and sold as a reagent or a purified product can be used, or a compound prepared by extracting from a raw material such as the peel of a citrus (citron, orange, etc.) can also be used.

[0028] <α-glucosyl rutin> The α-glucosyl rutin (also referred to as α-glucosyl rutin) is a general term for compounds in which one or more glucose molecules are added to the glucose residue in the rutoside residue of rutin via an α 1→4 bond. The α-glucosyl rutin in the present application can be composed of one of the compounds having this structure alone, or can be a mixture of two or more.

[0029] The α-glucosyl rutin can be represented by the following formula (2). In formula (2), n is an integer of 0 or 1 or more, for example, an integer of 1 to 19.

[0030] [Chemical Formula 2]

[0031] The α-glucosyl rutin is a compound included as a main component in a product called “enzyme-treated rutin” (sometimes also referred to as “glycosylated rutin”). Among the α-glucosyl rutin, the one in which only one glucose is bonded is referred to as “α-monoglucosyl rutin”, and the one in which two or more glucoses are bonded is referred to as “α-polyglucosyl rutin”. That is, in formula (2), the α-monoglucosyl rutin is a compound in which n is 0, and the α-polyglucosyl rutin is generally a compound in which n is an integer of 1 to 19.

[0032] Enzyme-treated rutin is an aggregate of compounds produced by enzyme treatment of rutin in relation to the sugar thereof, and generally contains a mixture of compounds having different numbers of glucose bonded to rutin, such as a mixture composed of α-monoglucosyl rutin and α-polylucosyl rutin. Furthermore, since enzyme-treated rutin is generally produced by enzyme treatment, it can contain unreacted rutin and other derivatives, such as isoquercitrin. In addition, isoquercitrin (sometimes also referred to as isoquercetin) is a compound in which a β-D-glucose is bonded to the hydroxyl group at position 3 of the quercetin skeleton, in other words, a compound in which the rhamnose residue in the rutoside residue of rutin is cleaved.

[0033] Enzyme-treated rutin is, for example, a product obtained by allowing a glycosyltransferase (an enzyme having a function of adding glucose to rutin, such as cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19)) to act on rutin in the presence of an α-glucosyl sugar compound (cyclodextrin, a partial degradation product of starch, or the like) as a sugar donor (referred to herein as "first enzyme-treated rutin").

[0034] The first enzyme-treated rutin is a composition containing various α-glucosyl rutins having different numbers of glucose bonded thereto, i.e., an aggregate composed of α-monoglucosyl rutin and α-polylucosyl rutin, and rutin as an unreacted substance. If necessary, the first enzyme-treated rutin can be purified by using, for example, a porous synthetic adsorbent material and a suitable eluent to remove the sugar donor and other impurities and further reduce the content of rutin, so that a first enzyme-treated rutin having improved purity of α-glucosyl rutin (α-glucosyl rutin purified product) can be obtained.

[0035] In addition, in α-glucosyl rutin obtained by treating the first enzyme-treated rutin with an enzyme having glucoamylase activity that cleaves α-1,4-glycosidic bonds at glucose units, such as glucoamylase (EC 3.2.1.3), and adding a plurality of glucoses, only one glucose residue is added directly to the glucose residue in the rutoside residue of rutin itself, and the glucose residues other than this are cleaved, so that enzyme-treated rutin containing a large amount of α-monoglucosyl rutin (referred to herein as "second enzyme-treated rutin") can be obtained. By this enzyme treatment, the glucose residue in the rutoside residue bonded directly to the quercetin skeleton is not cleaved from the quercetin skeleton.

[0036] In the vascular endothelial function improver of an embodiment of the present application, if the effects of the present application and the like are taken into consideration, it is preferable to use a composition containing α-glucosyl rutin, i.e., enzyme-treated rutin, and a composition containing either of the first enzyme-treated rutin and the second enzyme-treated rutin can be used.

[0037] If the effects of the present application are considered, the enzyme-treated rutin is preferably a mixture containing at least α-glucosylrutin, and further containing isoquercitrin. Such a mixture can be produced by the following steps: (i) preparing the above-described first enzyme-treated rutin, (ii) treating the first enzyme-treated rutin with an enzyme having glucoamylase activity to convert almost all of the α-glucosylrutin to α-monoglucosylrutin, (iii) simultaneously treating with an enzyme having rhamnodiastase activity to convert almost all of the unreacted rutin to isoquercitrin.

[0038] As a commercially available product of the enzyme-treated rutin, for example, "αG Rutin PS", "αG Rutin P", "αG Rutin H", and the like, manufactured by Toyo Sugar Refining Co., Ltd. can be exemplified. "αG Rutin PS" is a composition containing 65 mass% of α-monoglucosylrutin and 15 mass% of isoquercitrin. Further, "αG Rutin P" is a composition containing 60 mass% of α-glucosylrutin, 10 mass% of rutin, and 1% of isoquercitrin.

[0039] As the α-glucosylrutin, α-monoglucosylrutin is preferred. This is because the molecular weight of α-monoglucosylrutin is smaller than that of α-polylucosylrutin, and thus the number of molecules per unit mass of α-monoglucosylrutin is larger, which is advantageous in terms of the effects.

[0040] The presence of various α-glucosylrutins and other components contained in the enzyme-treated rutin can be confirmed by HPLC chromatography, and the content of each component or the purity of a specific component desired can be calculated from the peak area of the chromatogram.

[0041] The method for producing α-glucosylrutin is not particularly limited, and a publicly known method can be used. It is preferred to produce by the above-described enzyme treatment of rutin because the yield is good and the production is easy. The rutin to be used is not particularly limited, and a compound generally produced and sold as a reagent or a purified product can be used, or a compound prepared by extraction from a raw material such as the peel of a citrus fruit (citrus, orange, etc.) or buckwheat seeds can be used.

[0042] <Improver of vascular endothelial function> The improver of vascular endothelial function of one embodiment of the present application contains α-glucosylhesperidin and α-glucosylrutin, and preferably contains α-monoglucosylhesperidin and α-monoglucosylrutin from the viewpoint of achieving a more excellent effect of improving the vascular endothelial function through the synergistic effect of α-glucosylhesperidin and α-glucosylrutin. In addition to these components, a publicly known arbitrary component such as an excipient, a lubricant, a stabilizer, a binder, a sweetening agent, a disintegrant, a humectant, a coloring agent, a coating agent, an emulsifying agent, and the like can be contained as long as the effect of improving the vascular endothelial function is not hindered.

[0043] From the viewpoint of achieving a more excellent vascular endothelial function improving effect by the synergistic effect of α-glucosyl hesperidin and α-glucosyl naringin, in the vascular endothelial function improving agent, the content of α-glucosyl naringin relative to 100 parts by mass of α-monoglucosyl hesperidin as α-glucosyl hesperidin and α-glucosyl naringin is preferably 20 to 500 parts by mass. As the lower limit of the content of α-glucosyl naringin relative to 100 parts by mass of α-monoglucosyl hesperidin, more preferably 20 parts by mass, further preferably 65 parts by mass, particularly preferably 120 parts by mass. In addition, as the upper limit of the content of α-glucosyl naringin relative to 100 parts by mass of α-monoglucosyl hesperidin, more preferably 500 parts by mass, further preferably 350 parts by mass, particularly preferably 200 parts by mass. Within the above content range, the range can be arbitrarily set to a range in which the above lower limit and upper limit are arbitrarily combined.

[0044] The content of α-glucosyl hesperidin and α-glucosyl naringin contained in the vascular endothelial function improving agent is not particularly limited. For example, as the lower limit of the content of α-glucosyl hesperidin or α-glucosyl naringin contained in the vascular endothelial function improving agent, 1% by mass, 2% by mass, 5% by mass, 10% by mass, 15% by mass can be exemplified. In addition, as the upper limit of the content of α-glucosyl hesperidin or α-glucosyl naringin contained in the vascular endothelial function improving agent, 99% by mass, 98% by mass, 95% by mass, 90% by mass, 85% by mass can be exemplified. As the content range of α-glucosyl hesperidin or α-glucosyl naringin contained in the vascular endothelial function improving agent, the range can be arbitrarily set to a range in which the above lower limit and upper limit are arbitrarily combined, for example, the range can be set to 1 to 99% by mass, 2 to 98% by mass, 5 to 95% by mass, or the like. However, the total content of α-glucosyl hesperidin and α-glucosyl naringin does not exceed 100% by mass. Within the above range, the content of α-glucosyl naringin relative to 100 parts by mass of α-monoglucosyl hesperidin is more preferably 20 to 500 parts by mass.

[0045] The vascular endothelial function improving agent is useful for maintaining the flexibility of blood vessels which decreases with age, because it has an effect of improving the function of vascular endothelial cells, that is, the vascular endothelial function.

[0046] The vascular endothelial function improving effect can be evaluated, for example, by the FMD test described later in the examples. The vascular endothelial function improving effect can be evaluated by the increase rate (%) of the FMD value (%) after the vascular endothelial function improving agent is taken relative to the FMD value (%) at the start of the taking, although it varies depending on the intake amount and intake period of α-glucosyl hesperidin and α-glucosyl naringin. As the vascular endothelial function improving effect, for example, the increase rate is preferably greater than 100%, more preferably 140% or more.

[0047] Further, the amount of change in the FMD value (%) obtained by subtracting the FMD value (%) at the start of ingestion from the FMD value (%) after ingestion can also be used to evaluate the vascular endothelial function improvement effect, and for example, when α-glucosyl hesperidin and α-glucosyl rutin are used in combination, a difference in the amount of change indicates a vascular function improvement effect, and particularly, a significant difference indicates an excellent vascular endothelial function improvement effect, as compared with a placebo, α-glucosyl hesperidin alone, or α-glucosyl rutin alone.

[0048] The amount of ingestion of the vascular endothelial function improver can be appropriately selected according to the age, sex, race, and the like of the ingester, and for example, 17 to 1000 mg, more preferably 70 to 500 mg, of α-monoglucosyl hesperidin per day is preferable. Further, 20 to 500 mg, more preferably 65 to 350 mg, of α-monoglucosyl rutin per day is preferable. The above-mentioned per day is the amount of administration, and for example, the administration can be performed in 1 to 3 times, or in 2 or 3 times. The administration period of the vascular endothelial function improver can be appropriately selected according to the age, sex, race, and the like of the ingester, and 14 to 84 days, more preferably 28 to 56 days, is preferable.

[0049] The vascular endothelial function improver can be ingested directly, or can be ingested in the form of a food containing the vascular endothelial function improver described below.

[0050] <Food containing a vascular endothelial function improver> An embodiment of the present application is a food containing the above-described vascular endothelial function improver, and the food also includes a beverage. As the food, beverages such as fruit beverages, oolong tea, green tea, black tea, cocoa, vegetable juice, green juice, soy milk, milk beverages, lactic acid beverages, near water beverages (Japanese: Nia Water), sports beverages, nutritional beverages, and the like; Western or Japanese confections such as jelly, pudding, candy, gummy candy, chewing gum, pressed tablet candy (lemonade), and yogurt; seasonings, fish processed products, livestock processed products; and health functional foods such as specified health foods, nutritional functional foods, and functional foods with a label, and other so-called health foods and supplements, feed, and pet foods can be exemplified.

[0051] The food containing the vascular endothelial function improver can be manufactured by adding the vascular endothelial function improver according to a conventional method. The vascular endothelial function improver can be added at the beginning of the manufacturing process of the food, or can be added at the middle or the end of the manufacturing process, and the method of addition can be appropriately selected from mixing, kneading, dissolving, impregnating, scattering, spraying, coating, and the like according to the form of the food.

[0052] The amount of the vascular endothelial function improver incorporated in the food is not particularly limited, and is preferably 0.014 to 25% by mass of α-glucosyl hesperidin, more preferably 0.14 to 12.5% by mass, and preferably 0.024 to 25% by mass of α-glucosyl rutin, more preferably 0.24 to 21.6% by mass, from the viewpoints of easiness of ingestion and stability in the food. Examples

[0053] The present application is more specifically described below based on examples, but the present application is not limited by these examples, and can be appropriately changed within the scope of the technical idea thereof to be implemented.

[0054] The FMD value (%) in the examples and comparative examples was measured using an FMD measuring device (product name: UNEX EF-18VG) manufactured by UNEX Corporation. The measurement method was performed in accordance with the international guidelines for FMD value measurement (Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39(2): 257-65.). Specifically, after measuring the brachial artery diameter at rest, the cuff was inflated to 200 mmHg and maintained for 5 minutes. Then, the cuff was rapidly deflated, and the arterial diameter was continuously monitored. The FMD value (%) was calculated according to the following formula. FMD value (%) = (maximum diameter - diameter at rest) x 100 / diameter at rest

[0055] [Example 1] To evaluate the synergistic effect of α-glucosyl hesperidin (αG hesperidin) and α-glucosyl rutin (αG rutin) used in combination, a non-blind pre-post control test was performed as follows.

[0056] A group of 9 healthy adult male and female subjects (8 males, 1 female) shown in Table 1 below were caused to ingest αG hesperidin PA-T (manufactured by Toyo Sugar Refining Co., Ltd.: containing 75 mass% of α-glucosyl hesperidin per unit of αG hesperidin PA-T dry matter) 100 mg and αG rutin PS (manufactured by Toyo Sugar Refining Co., Ltd.: containing 65 mass% of α-glucosyl rutin per unit of αG rutin PS dry matter) 200 mg with water or warm water on an empty stomach once a day for 4 weeks. The FMD value (%) was measured just after the first ingestion and just after the 4-week ingestion. The FMD value (%) just after the first ingestion was recorded as "initial FMD value (%)", and the FMD value (%) just after the 4-week ingestion was recorded as "4-week FMD value (%)". The change in the FMD value (%) after the 4-week ingestion (= 4-week FMD value (%) - initial FMD value (%)) was calculated. The results are shown in Figure 1 (A). The P value was calculated by t-test with αG hesperidin PA-T 100 mg of Comparative Example 1 below as a control, and p < 0.05 was considered to be a significant difference. In addition, the increase / decrease rate (%) of the 4-week FMD value (%) was calculated when the initial FMD value (%) was taken as 100. The results are shown in Figure 1 (B).

[0057] [Comparative Example 1] A group of 8 healthy adult male and female subjects (7 males, 1 female) shown in Table 1 below were caused to ingest αG hesperidin PA-T (manufactured by Toyo Sugar Refining Co., Ltd.: containing 75 mass% of α-glucosyl hesperidin per unit of αG hesperidin PA-T dry matter) 100 mg instead of αG hesperidin PA-T 100 mg and αG rutin PS 200 mg, and the change in the FMD value (%) and the increase / decrease rate (%) were calculated in the same manner as in Example 1. The results are shown in Figure 1 (A) and Figure 1 (B).

[0058] [Comparative Example 2] A group of 7 healthy adult male and female subjects (5 males, 2 females) shown in Table 1 below were caused to ingest αG rutin PS 200 mg instead of αG hesperidin PA-T 100 mg and αG rutin PS 200 mg, and the change in the FMD value (%) and the increase / decrease rate (%) were calculated in the same manner as in Example 1. The results are shown in Figure 1 (A) and Figure 1 (B).

[0059] [Comparative Example 3] The amount of change and the increase / decrease rate (%) of the FMD value (%) were calculated in the same manner as in Example 1, except that the group of healthy adult male and female subjects (7 males and 1 female) shown in Table 1 below ingested aG rutin PS 300 mg instead of aG hesperidin PA-T 100 mg and aG rutin PS 200 mg. The results are shown in Figure 1 (A) and Figure 1 (B).

[0060] [Comparative Example 4] The amount of change and the increase / decrease rate (%) of the FMD value (%) were calculated in the same manner as in Example 1, except that the group of healthy adult male and female subjects (4 males and 0 females) shown in Table 1 below ingested aG hesperidin PA-T 300 mg instead of aG hesperidin PA-T 100 mg and aG rutin PS 200 mg. The results are shown in Figure 1 (A) and Figure 1 (B).

[0061] [Table 1] Mean ± standard deviation (Mean ± SD)

[0062] [Example 2] Next, in order to evaluate the synergistic effect of aG hesperidin and aG rutin in combination, a double-blind parallel group comparison test was performed as follows.

[0063] The group of healthy adult male and female subjects (3 males and 9 females) shown in Table 2 below ingested aG hesperidin PA-T 100 mg and aG rutin PS 200 mg with water or warm water on an empty stomach once a day for 8 weeks. The FMD value (%) was measured immediately after the first ingestion and after 8 weeks of ingestion. The FMD value (%) obtained immediately after the first ingestion was recorded as "initial FMD value (%)", and the FMD value (%) after 8 weeks of ingestion was recorded as "FMD value (%) after 8 weeks". The amount of change in the FMD value (%) after 8 weeks of ingestion (= FMD value (%) after 8 weeks - initial FMD value (%)) was calculated. The results are shown in Figure 2 The P value was calculated by t-test with the placebo described below as a control, and p < 0.05 was considered to be a significant difference.

[0064] In addition, the group of healthy adult male and female subjects (2 males and 7 females) as a placebo group ingested a placebo instead of aG hesperidin PA-T and aG rutin PS, the placebo containing partially aG starch 200 mg and sugar alcohol 75 mg.

[0065] [Comparative Example 5] The change in the FMD value (%) was calculated in the same manner as in Example 2, except that the following group of healthy adult male and female subjects (3 males and 6 females) shown in Table 2 ingested aG Hesperidin PA-T 100 mg, but not aG Hesperidin PA-T 100 mg and aG Rutin PS 200 mg. The results are shown in Table 3. Figure 2 .

[0066] [Table 2] Mean ± SD

[0067] From the results of Figure 1 and Figure 2 it was confirmed that the FMD value (%) was improved in the case of simultaneous ingestion of aG Hesperidin and aG Rutin, as compared with the case of ingestion of aG Hesperidin alone and the case of ingestion of aG Rutin alone. Thus, it was seen that the vascular endothelial function improving effect was achieved by the synergistic effect of aG Hesperidin and aG Rutin.

Claims

1. A vascular endothelial function improving agent comprising α-glucosyl hesperidin and α-glucosyl rutin.

2. The vascular endothelial function improving agent according to claim 1, comprising α-monoglucosyl hesperidin and α-monoglucosyl rutin.

3. The vascular endothelial function improving agent according to claim 2, wherein The content of α-monoglucosylrutin is 20 to 500 parts by mass relative to 100 parts by mass of α-monoglucosylhesperidin. A food comprising the vascular endothelial function improving agent according to claim 1.

Images