TW202339713A - Composition for improving flexibility of blood vessels, composition for improving vascular endothelial function, composition for inhibiting platelet aggregation, composition for improving blood flow, and transoral composition being characterized by containing (A) catechin and (B) proanthocyanidin B3 - Google Patents

Abstract

This invention relates to a composition, characterized by containing (A) catechin and (B) proanthocyanidin B3, and the mass ratio [(A)/(B)] of the content of the component (A) to the content of the component (B) in the composition is greater than 0.60 and less than 15. The composition according to the present invention is excellent in effects of improving the flexibility of blood vessels, improving the vascular endothelial functions, improving a blood flow and inhibiting platelet aggregation, and can be used as a composition for improving the flexibility of blood vessels, a composition for improving vascular endothelial functions, a composition for improving a blood flow, and a composition for inhibiting platelet aggregation.

Description

Composition for improving blood vessel flexibility, composition for improving vascular endothelial function, composition for inhibiting platelet aggregation, composition for improving blood flow, and oral composition

The present invention relates to a composition for improving blood vessel flexibility, a composition for improving blood flow, a composition for improving vascular endothelial function, a composition for inhibiting platelet aggregation, and an oral composition, which are characterized in that they contain (A ) catechin and (B) procyanidin B3 (hereinafter also referred to as "PB3"), and the mass ratio of the content of component (A) to the content of component (B) in the above composition [(A) /(B)] is above 0.60 and below 15.

In recent years, lifestyle-related diseases have been increasing due to changes in diet or lifestyle. Lifestyle diseases are a general term for diseases such as hypertension, hyperlipidemia, and diabetes, as well as diseases such as angina pectoris, myocardial infarction, and cerebral circulation disorders that are generally believed to be preventable by improving lifestyle habits. As one of the causes of these diseases, it is known that it is related to thrombosis and reduced blood flow caused by reduced blood vessel flexibility, reduced vascular endothelial function, or increased platelet aggregation ability. In addition, since lifestyle-related diseases are chronic diseases, their prevention or treatment requires a long time. Therefore, the industry hopes to develop foods that can safely and effectively improve blood vessel flexibility, improve blood flow, improve vascular endothelial function and inhibit platelet aggregation in the long term. As food materials having such an action, for example, hops (Patent Document 1), chlorogenic acid (Patent Document 2), and piperine (Patent Document 3) are known. [Prior technical literature] [Patent Document]

[Patent Document 1] US2006/0147568A1 [Patent Document 2] Japanese Patent Application Laid-Open No. 2003-261444 [Patent Document 3] Japanese Patent Publication No. 2020-090551

[Problem to be solved by the invention]

However, according to investigations by the present inventors, hops, chlorogenic acid, and piperine are not sufficient to improve blood vessel flexibility, improve blood flow, improve vascular endothelial function, and inhibit platelet aggregation.

Therefore, the present inventors focused on (A) catechin and (B) proanthocyanidin B3, and conducted various studies on the subject of effectively utilizing these components.

The present inventors conducted intensive investigations and studies, and found that by setting the content of (A) catechin and (B) proanthocyanidin B3 to a specific ratio, excellent blood vessel flexibility improvement effects and blood flow improvement can be exerted. effect, improving vascular endothelial function and inhibiting platelet aggregation. The present invention is completed based on the relevant knowledge.

The content of the present invention is as follows. [1] A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood vessel flexibility, and the content of component (A) in the composition is relative to component (B) ) content, the mass ratio [(A)/(B)] is 0.60 or more and 15 or less. [2] The composition according to [1], which is a composition for improving blood vessel flexibility. [3] The composition according to [1] or [2], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is: Above 0.60 and below 5.42. [4] Use of a composition for producing a blood vessel flexibility improving agent or a food for improving blood vessel flexibility, wherein the composition contains components (A) catechin and (B) proanthocyanidin B3 as a component for improving blood vessel flexibility. For active ingredients, the mass ratio [(A)/(B)] of the content of component (A) relative to the content of component (B) is 0.60 or more and 15 or less. [5] The use according to [4], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 or more and 5.42 or less.

[6] A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood flow, and the content of component (A) in the composition is relative to component (B) The mass ratio of the content [(A)/(B)] is 0.60 or more and 15 or less. [7] The composition according to [6], which is a composition for improving blood flow. [8] The composition according to [6] or [7], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is: Above 0.60 and below 5.42. [9] Use of a composition for producing a blood flow improving agent or a blood flow improving food, wherein the composition contains (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood flow. Or, the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the above composition is 0.60 or more and 15 or less. [10] The use according to [9], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 or more and 5.42 or less.

[11] A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving vascular endothelial function, and the content of component (A) in the composition is relative to component (B) ) content, the mass ratio [(A)/(B)] is 0.60 or more and 15 or less. [12] The composition according to [11], which is a composition for improving vascular endothelial function. [13] The composition according to [11] or [12], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is: Above 0.60 and below 5.42. [14] Use of a composition for producing a vascular endothelial function improving agent or a food for improving vascular endothelial function, wherein the composition contains (A) catechin and (B) proanthocyanidin B3 as a vascular endothelial function improving agent As an active ingredient, the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the above composition is 0.60 or more and 15 or less. [15] The use according to [14], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 or more and 5.42 or less.

[16] A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for inhibiting platelet aggregation, and the content of component (A) in the composition is relative to component (B) The mass ratio of the content [(A)/(B)] is 0.60 or more and 15 or less. [17] The composition according to [16], which is a composition for inhibiting platelet aggregation. [18] The composition according to [16] or [17], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is: Above 0.60 and below 1.67. [19] Use of a composition for producing a platelet aggregation inhibitor or a food for platelet aggregation inhibition, wherein the composition contains (A) catechin and (B) proanthocyanidin B3 as an active ingredient for inhibiting platelet aggregation. Or, the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the above composition is 0.60 or more and 15 or less. [20] The use according to [19], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 or more and 1.67 or less.

[21] An oral composition containing (A) catechin and (B) proanthocyanidin B3, and the mass ratio of the content of component (A) to the content of component (B) in the composition is [ (A)/(B)] is 0.60 or more and 15 or less. [22] The composition according to [21], wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.75 or more and 10.3 or less .

[23] As described in any one of [1] to [3], [6] to [8], [11] to [13], [16] to [18], [21] to [22] Compositions containing pine bark extract.

[24] The use as described in any one of [4], [5], [9], [10], [14], [15], [19] and [20], wherein the above composition contains pine Bark Extract. [Effects of the invention]

According to the present invention, a composition containing (A) catechin and (B) proanthocyanidin B3 can be provided, and by setting the content of (A) catechin and (B) the content of proanthocyanidin B3 to a specific ratio, It has an excellent effect of improving blood vessel flexibility and can be used as an oral composition, and a use of the composition for improving blood vessel flexibility is provided.

According to the present invention, a composition containing (A) catechin and (B) proanthocyanidin B3 can be provided, and by setting the content of (A) catechin and (B) the content of proanthocyanidin B3 to a specific ratio, It has an excellent blood flow improving effect and can be used as an oral composition, and a use of the composition for improving blood flow is provided.

According to the present invention, a composition containing (A) catechin and (B) proanthocyanidin B3 can be provided, and by setting the content of (A) catechin and (B) the content of proanthocyanidin B3 to a specific ratio, It has an excellent effect of improving vascular endothelial function and can be used as an oral composition, and a use of the composition for improving vascular endothelial function is provided.

According to the present invention, a composition containing (A) catechin and (B) proanthocyanidin B3 can be provided, and by setting the content of (A) catechin and (B) the content of proanthocyanidin B3 to a specific ratio, The composition has excellent platelet aggregation inhibitory effect and can be used as an oral composition, and a use of the composition for platelet aggregation inhibition is provided.

Combination for producing the composition for improving blood vessel flexibility, the composition for improving blood flow, the composition for improving vascular endothelial function, the composition for inhibiting platelet aggregation, the agent for improving blood vessel flexibility or the food for improving blood vessel flexibility of the present invention Compositions for producing blood flow improving agents or foods for improving blood flow, compositions for producing vascular endothelial function improving agents or foods for improving vascular endothelial functions, compositions for producing platelet aggregation inhibitors or platelet aggregation inhibitors Food compositions and oral compositions (hereinafter collectively referred to as "compositions of the present invention"; however, when there are special instructions, compositions for specific uses will be described) containing (A) catechin and ( B) Proanthocyanidin B3, the mass ratio of the content of component (A) catechin to the content of component (B) proanthocyanidin B3 is 0.60 or more and 15 or less. This is useful for the blood vessel flexibility improving agent, blood vessel flexibility improving food, blood flow improving agent, blood flow improving food, vascular endothelial function improving agent, vascular endothelial function improving food, platelet aggregation inhibitor, and platelet aggregation inhibiting food of the present invention. The same goes for food. The composition of the present invention may further contain other ingredients if necessary. In addition, the matters described below do not limit the present invention, and various changes can be made within the scope of the spirit of the present invention. Each component and the composition of the present invention will be described below.

＜1. Regarding the use of improving blood vessel flexibility＞ First, the composition and oral composition used in the composition for improving blood vessel flexibility, the agent for improving blood vessel flexibility, or the food for improving blood vessel flexibility of the present invention will be described. The composition of the composition described below can also be directly applied to blood vessel flexibility improving agents and blood vessel flexibility improving foods.

In addition to improving the flexibility (elasticity) of blood vessels, the improvement of blood vessel flexibility in the present invention also refers to the improvement of arteriosclerosis. Examples of methods for measuring vascular flexibility include evaluation by flow-dependent vasodilatation (FMD) in clinical trials or plethysmography, and evaluation using animal experiments other than humans. Or use in vitro (in vitro) indicators such as endothelial cell NO synthase gene expression or prostaglandin I2 production to evaluate.

(1-1) Catechin The composition of the present invention contains (A) catechin. Catechin is a compound represented by the chemical formula C ₁₅ H ₁₄ O _6. The catechin in the present invention is (+)-catechin represented by the following chemical formula (1), or (+)-catechin represented by the chemical formula (2) (-)-Catechin. As the catechin, either (+)-catechin or (-)-catechin can be used, or two of them can be used in combination. From the viewpoint of the blood vessel flexibility improving effect, it is preferable to use Use 2 combinations.

[Chemical 1]

The catechins of the present invention can be synthesized or plant-derived substances such as pine and tea. From the viewpoint of safety during use, plant-derived substances are preferred and from the viewpoint of being rich in catechins, More preferably, it is pine, and particularly preferably, pine bark is used.

The blending ratio of the catechins blended in the composition of the present invention can be appropriately set within a wide range depending on various conditions such as purpose, shape, and intended use. For example, when the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000001 to 5.0% by mass, in terms of blood vessel flexibility. From the viewpoint of improvement effect, the content is more preferably 0.00001 to 3.0 mass%, and particularly preferably 0.0001 to 1.0 mass%. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%.

The amount of catechins in the composition of the present invention can be analyzed by HPLC (High Performance Liquid Chromatography). For example, measurement can be performed by an HPLC analysis device equipped with an ultraviolet external absorption detector. The analysis column can use L-Column ODS 3 μm (4.6×250 mm) manufactured by Chemical Substances Evaluation and Research Institute as the liquid of the mobile phase. As media, you can use 0.1 M acetic acid aqueous solution (mobile phase A) or 0.1 M acetic acid-acetonitrile solution (mobile phase B). The column temperature can be set to 40°C, and the flow rate can be set to 1.0 mL/min. Gradient conditions can be set as follows.

[Table A] time (minutes) A liquid (%) B liquid (%) 0 95 5 5 95 5 25 85 15 30 10 90 45 10 90 45.01 95 5 55 95 5

In the present invention, examples of pine that can be used as a source of catechins include French maritime pine, larch, black pine, red pine, white pine, five-needle pine, red pine, Japanese pine, Ryukyu pine, American pine, and longleaf pine. , whitebark pine, Anneda from Quebec, Canada, and other plants belonging to the order Pinales, but are not limited to these. Among these, the French maritime pine (Pinus pinaster), a maritime pine that grows on the Atlantic coast of southern France, is preferred from the viewpoint of confirmed food safety and high concentration of catechins.

The processing method of plant-derived substances is not particularly limited, and processed products such as crushed products, juices, and extracts can be used. Examples of the pulverized product include powder, granules, and the like. Juice or extract can be in liquid form or can be used in the form of a paste or dry powder. When it is in the form of a paste or a dry powder, it can be produced using only the substance, or it can be processed together with excipients. In the present invention, from the viewpoint of the effect of improving blood vessel flexibility, it is preferably obtained by extraction. Hereinafter, the extraction method of plant-derived substances will be explained, taking the manufacturing method of pine bark extract as an example.

Pine bark extract can be obtained by extracting pine bark with a solvent. Examples of the solvent include, but are not limited to, water, organic solvents, and water-containing organic solvents (water-containing alcohols such as water-containing ethanol). As the organic solvent used for extraction, organic solvents generally allowed when extracting natural components can be used. For example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 2-butanol can be used. , butane, acetone, hexane, cyclohexane, propylene glycol, aqueous ethanol, aqueous propylene glycol, methyl ethyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, methylene chloride, edible fats and oils, 1,1 ,1,2-tetrafluoroethane, and 1,1,2-trichloroethylene, etc. These solvents can be obtained using one type alone or in combination of two or more types. The temperature during extraction can be appropriately adjusted from room temperature to a temperature below the boiling point of the extraction solvent. In the present invention, from the viewpoint of efficiently extracting catechins, it is preferable to use water, hydrous ethanol, and hydrous propylene glycol.

The extraction method is not particularly limited as long as it is a method generally allowed for extracting natural components. Examples include solid-liquid extraction methods such as heated extraction and supercritical fluid extraction.

The heating extraction method is, for example, a method in which the test substance is brought into contact with a solvent, and the components contained in the test substance are extracted into the solvent by processing the test substance at a temperature below the boiling point of the solvent. It can also be a reflux extraction method.

The supercritical fluid extraction method is, for example, a method of extracting using a supercritical fluid, which is a fluid in a state exceeding the gas-liquid critical point (critical temperature, critical pressure) of a substance. Examples of the supercritical fluid include carbon dioxide, ethylene, propane, nitrous oxide (laughing gas), etc., and carbon dioxide is preferred.

In the supercritical fluid extraction method, an extraction step of extracting a target component with a supercritical fluid and a separation step of separating the target component from the supercritical fluid are performed. In the separation step, any one of extraction separation based on pressure change, extraction separation based on temperature change, and extraction separation using adsorbent/absorbent can be performed.

Supercritical fluid extraction can also be performed by entrainer addition. This method is to add about 2 to 20 W/V% of ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, and ketones to the extraction fluid. This fluid is subjected to supercritical fluid extraction, thereby dramatically increasing the solubility of target extracts such as OPC (oligomeric pro anthocyanidin) and catechins in the extraction solvent, or enhancing the separation selectivity. This method efficiently obtains pine bark extract.

Since the supercritical fluid extraction method can be operated at a relatively low temperature, it has the following advantages: it can also be applied to substances that will deteriorate and decompose at high temperatures; it does not retain the extraction fluid; and it can recycle solvents. , so the desolvation step, etc. can be omitted, thereby simplifying the steps.

In addition to the above-mentioned extraction methods, extraction from pine bark can also be carried out by liquid carbon dioxide batch method, liquid carbon dioxide reflux method, and supercritical carbon dioxide reflux method.

Extraction from pine bark can also combine multiple extraction methods. By combining multiple extraction methods, pine bark extracts of various compositions can be obtained.

In terms of safety, pine bark extracts obtained by extraction are preferably obtained by ultrafiltration, column methods using adsorbent carriers (Diaion HP-20, Sephadex-LH20, and chitin, etc.), and batch methods. Perform purification.

Extraction From the viewpoint of preservation and processability, the pine bark extract is preferably in powder form, and more preferably in dry powder form. The drying method is not particularly limited, and examples thereof include drying methods such as heating, sun-drying, hot-air drying, freeze-drying, and decompression of the pine bark extract containing a solvent. The degree of drying is sufficient to confirm that the solvent content of the pine bark extract has been sufficiently reduced, for example, the solvent content is 10 wt% or less, preferably 5 wt% or less.

As a method of powdering to obtain dry powder of pine bark extract, for example, a method commonly used by manufacturers, that is, a method of crushing and powdering pine bark extract by a ball mill, a hammer mill, a roller mill, etc. , but are not limited to these. The order of drying and powdering can also be changed, and the pine bark extract before drying can be pulverized in advance, and the pulverized material can be dried to prepare dried pine bark extract powder.

Pine bark extracts may also be commercially available. Examples of commercially available pine bark extracts include Frevanazine (registered trademark; Toyo Shinyaku Co., Ltd.) and the like.

(1-2)About PB3 The composition of the present invention contains (B) proanthocyanidin B3 (PB3). Proanthocyanidin B3 is a dimer obtained by C4-C8 bonding between (+)-catechin and (+)-catechin. (PB3) of the present invention can use synthetic materials or plant-derived substances such as pine, apple, cocoa, or grape. From the viewpoint of safety during use, plant-derived substances are preferred, and pine is more preferred. From the perspective of containing PB3, it is particularly preferable to use pine bark. The types of pine that can be used in the composition of the present invention and the processing methods of plant-derived substances can be referred to the contents described in catechins.

The blending ratio of PB3 blended in the composition of the present invention can be appropriately set within a wide range depending on various conditions such as purpose, shape, and intended use. For example, when the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000001 to 5.0% by mass, in terms of blood vessel flexibility. From the viewpoint of improvement effect, the content is more preferably 0.00001 to 3.0 mass%, and particularly preferably 0.0001 to 1.0 mass%. Furthermore, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%.

The amount of PB3 in the composition of the invention can be analyzed by HPLC. For example, measurement can be performed by an HPLC analysis device equipped with an ultraviolet external absorption detector. The analysis column can use L-Column ODS 3 μm (4.6×250 mm) manufactured by Chemical Substances Evaluation and Research Institute as the liquid of the mobile phase. The media can use 0.1 M acetic acid aqueous solution (mobile phase A), 0.1 M acetic acid-acetonitrile solution (mobile phase B), the column temperature can be set to 40°C, and the flow rate can be set to 1.0 mL/min. Gradient conditions can be set as follows.

[Table B] time (minutes) A liquid (%) B liquid (%) 0 95 5 5 95 5 25 85 15 30 10 90 45 10 90 45.01 95 5 55 95 5

(1-3)(A)/(B) ratio The composition of the present invention contains (A) catechin and (B) proanthocyanidin B3, and the mass ratio of the content of component (A) in the above composition to the content of component (B) [(A)/(B)] It is 0.60 or more and 15 or less, thereby having an excellent blood vessel flexibility improving effect. The lower limit of the mass ratio [(A)/(B)] of the content of component (A) relative to the content of component (B) is 0.60 or more, preferably 0.70 or more, especially from the viewpoint of the blood vessel flexibility improving effect. The best value is above 0.75. In addition, the upper limit of the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) is 15 or less, preferably 12 or less, from the viewpoint of the blood vessel flexibility improving effect. , more preferably 10.3 or less, still more preferably 7.63 or less, and particularly preferably 5.42 or less. It can also be below 2.11 or below 1.67.

From the perspective of being used to improve the flexibility of blood vessels, the composition of the present invention is not particularly limited as long as it can be distinguished from other products when used as a product. For example, the body, packaging, instructions, and promotional materials of the product of the present invention are not particularly limited. Those with a function of improving blood vessel flexibility are included in the scope of the present invention. Examples include pharmaceuticals (including quasi-drugs), so-called health foods such as foods for specific health uses, foods with nutritional functions, foods with functional labels, and other functional foods with functional labels approved by specific agencies. Examples of so-called healthy foods include labels such as "helps maintain the flexibility of blood vessels (the dilatation of blood vessels after blood vessel tightening) which decreases with age", "increases the dilation of blood vessels that maintains blood vessel tightening", " "Maintain the dilatation of blood vessels after blood vessel tightening", "increase the flexibility of blood vessels", "maintain the flexibility of blood vessels", "increase the elasticity of blood vessels", "maintain the elasticity of blood vessels", etc.

＜2. Regarding the use of blood flow improvement＞ Next, the blood flow improving composition of the present invention and the composition used for the production of a blood flow improving agent or a blood flow improving food will be described. The composition of the composition described below can also be directly applied to a blood flow improving agent or a blood flow improving food.

The improvement of blood flow in the present invention means both the improvement of blood fluidity and the improvement of blood flow rate and blood volume. Improving blood fluidity means reducing blood viscosity and improving blood circulation. On the other hand, the improvement of blood flow rate and blood volume means the improvement of blood flow rate and blood flow rate within blood vessels. Examples of blood flow measurement methods include evaluation by measurement of blood fluidity and blood flow in clinical trials, evaluation using animal experiments other than humans, and NO synthesis using endothelial cells. Evaluation based on in vitro indicators such as enzyme gene expression or prostaglandin I2 production.

(2-1)About catechins Preferred types of catechins are those described in "(1-1) Catechins" above. From the viewpoint of the blood flow improving effect, it is preferable to use a combination of two types of catechins: (+)-catechin and (-)-catechin. Furthermore, from the viewpoint of the blood flow improving effect, the catechin source preferably contains a pine bark extract. The extraction method is as described in (1-1) above.

The blending ratio of the catechins blended in the composition of the present invention can be appropriately set within a wide range depending on various conditions such as purpose, shape, and intended use. When the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), from the viewpoint of blood flow improving effect, it is preferably 0.000001 to 5.0 mass%, more preferably 0.00001 to 3.0 mass%, particularly preferably 0.0001 to 1.0 mass%. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%. The method for measuring the amount of catechin is as described in (1-1) above.

(2-2)About PB3 The preferred types of PB3 are all consistent with those described in "(1-2) About PB3" above.

The blending ratio of PB3 blended in the composition of the present invention can be appropriately set within a wide range depending on various conditions such as purpose, shape, and intended use. When the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000001 to 5.0 mass% in terms of blood flow improving effect. From a viewpoint, 0.00001 to 3.0 mass% is more preferable, and 0.0001 to 1.0 mass% is particularly preferable. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%. The method for measuring the amount of PB3 is as described in (1-2) above.

(2-3) About (A)/(B) ratio The composition of the present invention contains (A) catechin and (B) proanthocyanidin B3, and the mass ratio of the content of component (A) in the above composition to the content of component (B) [(A)/(B)] It is 0.60 or more and 15 or less, thereby having an excellent blood flow improving effect. The lower limit of the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) is 0.60 or more, preferably 0.70 or more, which is particularly preferred from the viewpoint of blood flow improving effect. is above 0.75. In addition, the upper limit of the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) is 15 or less, preferably 12 or less. From the viewpoint of the blood flow improving effect, It is more preferably 10.3 or less, still more preferably 7.63 or less, and particularly preferably 5.42 or less. It can also be below 2.11 or below 1.67.

From the perspective of being used to improve blood flow, the composition of the present invention is not particularly limited as long as it can be distinguished from other products when used as a product. For example, any of the body, packaging, instructions, and promotional materials of the product of the present invention. Those indicating the function of improving blood flow are included in the scope of the present invention. Examples include pharmaceuticals (including quasi-drugs), so-called health foods such as foods for specific health uses, foods with nutritional functions, foods with functional labels, and other functional foods with functional labels approved by specific agencies. Examples of so-called healthy foods include labels such as "helps maintain blood smoothness", "helps maintain blood fluidity", "helps maintain blood fluidity (platelet aggregation ability)", "improves blood flow". ", "Maintain blood flow", "Maintain healthy blood flow (peripheral blood flow)", "Increase the reduced peripheral blood flow and return it to normal", "Adjust the reduced blood flow (peripheral blood flow) to normal", etc. By.

＜3. Regarding the use of improving vascular endothelial function＞ Next, the vascular endothelial function-improving composition of the present invention and the composition used for the production of a vascular endothelial function-improving agent or a vascular endothelial function-improving food will be described. The composition of the composition described below can also be directly used as a vascular endothelial function improving agent or a food for improving vascular endothelial function.

The so-called vascular endothelial function in the present invention refers to the adjustment of vascular smooth muscle tension by releasing various vascular functional substances such as nitric oxide (NO), prostaglandin I2, and endothelial-derived hyperpolarizing factor (EDHF). In addition, it also refers to cells. Adhesion and other functions related to blood vessel protection. Examples of methods for measuring vascular endothelial function include evaluation by flow-dependent vasodilatation (FMD) in clinical trials or plethysmography. In addition, evaluation using animal experiments other than humans, Or it can be evaluated using in vitro indicators such as NO synthase gene expression or prostaglandin I2 production in endothelial cells.

(3-1)About catechins Preferred types of catechins are those described in "(1-1) Catechins" above. From the viewpoint of the vascular endothelial function-improving effect, it is preferable to use a combination of two types of catechins: (+)-catechin and (-)-catechin. Furthermore, from the viewpoint of the vascular endothelial function-improving effect, the catechin source preferably contains a pine bark extract. The extraction method is as described in (1-1) above.

The blending ratio of the catechins blended in the composition of the present invention can be appropriately set within a wide range depending on various conditions such as purpose, shape, and intended use. When the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000001 to 5.0% by mass, in terms of improving vascular endothelial function. From the viewpoint of this, 0.00001 to 3.0 mass% is more preferred, and 0.0001 to 1.0 mass% is particularly preferred. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%. The method for measuring the amount of catechin is as described in (1-1) above.

(3-2)About PB3 The preferred types of PB3 are all consistent with those described in "(1-2) About PB3" above.

The blending ratio of PB3 blended in the composition of the present invention can be appropriately set within a wide range depending on various conditions such as purpose, shape, and intended use. When the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000001 to 5.0% by mass, in terms of improving vascular endothelial function. From the viewpoint of this, 0.00001 to 3.0 mass% is more preferred, and 0.0001 to 1.0 mass% is particularly preferred. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%. The method for measuring the amount of PB3 is as described in (1-2) above.

(3-3) About (A)/(B) ratio The composition of the present invention contains (A) catechin and (B) proanthocyanidin B3, and the mass ratio of the content of component (A) in the above composition to the content of component (B) [(A)/(B)] It is between 0.60 and 15, which has an excellent effect on improving vascular endothelial function. The lower limit of the mass ratio [(A)/(B)] of the content of component (A) relative to the content of component (B) is 0.60 or more, preferably 0.70 or more, especially from the viewpoint of the vascular endothelial function improving effect. The best value is above 0.75. In addition, the upper limit of the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) is 15 or less, preferably 12 or less. From the viewpoint of the blood flow improving effect, It is more preferably 10.3 or less, still more preferably 7.63 or less, and particularly preferably 5.42 or less. It can also be below 2.11 or below 1.67.

From the perspective of being used to improve vascular endothelial function, the composition of the present invention is not particularly limited as long as it can be distinguished from other products when used as a product. For example, any of the body, packaging, instructions, and promotional materials of the product of the present invention. A substance with a function of improving vascular endothelial function is included in the scope of the present invention. Examples include pharmaceuticals (including quasi-drugs), so-called health foods such as foods for specific health uses, foods with nutritional functions, foods with functional labels, and other functional foods with functional labels approved by specific agencies. Examples of so-called healthy foods include labels such as "Improve vascular function," "Maintain vascular function," "Improve vascular endothelial function," "Maintain vascular endothelial function," "Improve vascular endothelial function of arteries weakened by age," and "Maintaining the endothelial function of arteries weakened by age" and so on.

＜4. Regarding the use of platelet aggregation inhibition＞ Next, the composition for inhibiting platelet aggregation of the present invention and the composition for producing a platelet aggregation inhibitor will be described. The composition of the composition described below can be directly applied to platelet aggregation inhibitors or platelet aggregation inhibiting foods.

Inhibition of platelet aggregation in the present invention means inhibition of platelet aggregation. Examples of methods for measuring platelet aggregation include evaluation by platelet aggregation rate in clinical trials, evaluation using animal experiments other than humans, and in vitro indicators such as prostaglandin I2 production. evaluate.

(4-1)About catechins Preferred types of catechins are those described in "(1-1) Catechins" above. From the viewpoint of the platelet aggregation inhibitory effect, it is preferable to use a combination of two types of catechins: (+)-catechin and (-)-catechin. Furthermore, from the viewpoint of platelet aggregation inhibitory effect, the catechin source preferably contains a pine bark extract. The extraction method is as described in (1-1) above.

Moreover, when the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000001 to 5.0% by mass in terms of platelet aggregation inhibition. From the viewpoint of action, 0.00001 to 3.0 mass% is more preferred, and 0.0001 to 1.0 mass% is particularly preferred. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%. The method for measuring the amount of catechin is as described in (1-1) above.

(4-2)About PB3 The preferred types of PB3 are all consistent with those described in "(1-2) About PB3" above.

When the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000001 to 5.0% by mass, in terms of platelet aggregation inhibitory effect. From a viewpoint, 0.00001 to 3.0 mass% is more preferable, and 0.0001 to 1.0 mass% is particularly preferable. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000001 to 1.0% by mass, more preferably 0.00001 to 1.0% by mass. 0.1 mass%, particularly preferably 0.0001 to 0.01 mass%. The method for measuring the amount of PB3 is as described in (1-2) above.

(4-3) About (A)/(B) ratio The composition of the present invention is characterized by containing (A) catechin and (B) proanthocyanidin B3, and the mass ratio of the content of component (A) to the content of component (B) in the composition is [(A)/ (B)] is 0.60 or more and 15 or less, thereby having an excellent platelet aggregation inhibitory effect. The lower limit of the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) is 0.60 or more, preferably 0.70 or more. In addition, the upper limit of the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) is not particularly limited as long as it is 15 or less, but it is preferably 12 or less, and more preferably It is 10.3 or less, more preferably 7.63 or less, still more preferably 5.42 or less. From the viewpoint of platelet aggregation inhibitory effect, it is particularly preferably 2.11 or less, and most preferably 1.67 or less.

From the viewpoint of being used for inhibiting platelet aggregation, the composition of the present invention is not particularly limited as long as it can be distinguished from other products when used as a product. For example, any of the body, packaging, instructions, and promotional materials of the product of the present invention. Those indicating the function of inhibiting platelet aggregation are included in the scope of the present invention. Examples include pharmaceuticals (including quasi-drugs), so-called health foods such as foods for specific health uses, foods with nutritional functions, foods with functional labels, and other functional foods with functional labels approved by specific agencies. Examples of so-called healthy foods include labels such as "maintains platelet aggregation ability", "helps maintain smoothness of blood (platelet aggregation ability)", "helps maintain blood fluidity (platelet aggregation ability)", "helps maintain To maintain blood fluidity (platelet aggregation ability)" and so on.

＜Others (common to all uses)＞ The blending ratio of the total amount of (A) catechin and (B) PB3 blended in the composition of the present invention is not particularly limited, and can be appropriately set within a wide range according to various conditions such as purpose, shape, and intended use. Mixing ratio. For example, when the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), it is preferably 0.000002 to 10% by mass, in terms of blood vessel flexibility. From the viewpoint of improving effect, vascular endothelial function improving effect, blood flow improving effect and platelet aggregation inhibiting effect, 0.00002 to 6.0 mass % is more preferred, and 0.0002 to 2.0 mass % is particularly preferred. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), it is preferably 0.000002 to 2.0% by mass, more preferably 0.00002 to 2.0% by mass. 0.2 mass%, particularly preferably 0.0002 to 0.02 mass%.

The daily intake of the composition of the present invention relative to the body weight is not particularly limited and can be appropriately set according to the usage pattern, the user's usage content, and the like. For example, when the composition of the present invention is a solid dosage form (powder, granular, granular, tablet, capsule, chewable tablet, etc.), the weight of the user is used as the standard, and it is preferably 0.2 to 6000. mg/kg, more preferably 1 to 4000 mg/kg, and particularly preferably 2 to 2000 mg/kg from the viewpoint of improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation. . For example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), the weight of the user is preferably 200 to 20,000. mg/kg, more preferably 600 to 15,000 mg/kg, and particularly preferably 1,000 to 10,000 mg/kg from the viewpoint of improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation. .

The amount of the composition of the present invention taken per serving relative to the body weight is also not particularly limited. For example, when the composition of the present invention is a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.), based on the user's body weight, it is preferably 0.06 to 0.06 6000 mg/kg, more preferably 0.3 to 4000 mg/kg, and particularly preferably 0.6 to 2000 mg/kg from the viewpoint of improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation. kg. Furthermore, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), the weight of the user is preferably 66 to 20,000. mg/kg, more preferably 200 to 15,000 mg/kg, and particularly preferably 333 to 10,000 mg/kg from the viewpoint of improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation. .

The daily intake amount of the composition of the present invention is not particularly limited, for example, when the composition of the present invention is in the form of a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.) When used, 0.01 to 300 g is preferred, and 0.05 to 200 g is more preferred. From the viewpoint of improving blood vessel flexibility, endothelial function, blood flow, and inhibiting platelet aggregation, 0.1 to 200 g is particularly preferred. 100g. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), 10 to 1000 g is preferred, and 30 to 750 g is more preferred. g. From the viewpoint of improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation, 50 to 500 g is particularly preferred.

The amount of the composition of the present invention that can be taken once is not particularly limited. For example, when the composition of the present invention is in the form of a solid preparation (powder, granular, granular, tablet, capsule, chewable tablet, etc.) When used, 0.003 to 300 g is preferred, and 0.01 to 200 g is more preferred. From the viewpoint of improving blood vessel flexibility, endothelial function, blood flow, and inhibiting platelet aggregation, 0.03 to 200 g is particularly preferred. 100g. Moreover, for example, when the composition of the present invention is a liquid (liquid, gel, paste, jelly, yogurt, etc.), 3.3 to 1000 g is preferred, and 10 to 750 is more preferred. g. From the viewpoint of improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation, 16 to 500 g is particularly preferred.

The composition of the present invention can be ingested at any time before a meal, between meals, after a meal, or during a meal, and is considered to be effective in improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation. In other words, it is preferably taken before, after, or during a meal, and more preferably before or during a meal.

The composition of the present invention may only contain catechin and PB3, but may also contain other ingredients in addition to these. As the above-mentioned other components, for example, proteins, dietary fibers such as water-soluble dietary fiber and insoluble dietary fiber, vitamins, minerals, algae, microorganisms such as lactic acid bacteria and yeast, etc. can be blended. Further examples include sugars such as dextrin and starch, oligosaccharides, sweeteners, sour agents, colorants, thickeners, gloss agents, excipients, nutritional adjuvants, binders, lubricants, stabilizers, and diluents. Agents, extenders, emulsifiers, food additives, and seasonings are commonly used in the food field as needed. The content of these other components can be appropriately selected depending on the form of the composition of the present invention, etc.

The form of the composition of the present invention is not particularly limited, and it can be in any form. For example, it is a form suitable for oral use. Specifically, it can include: powder, granular, granular, tablet, liquid, gel, paste, capsule such as hard capsule or soft capsule, and capsule tablet. Shape, tablet form, gel form, jelly form, gummy form, wafer form, biscuit form, cookie form, cake form, chewable tablet form, syrup form, bar form, and yogurt form. From the viewpoint of improving blood vessel flexibility, improving vascular endothelial function, improving blood flow, and inhibiting platelet aggregation, the composition of the present invention is preferably in the form of granules, tablets, capsules, or liquids, and more preferably Granular, tablet, capsule form. Here, the granular form refers to a composition obtained by granulating a powder, which can be consumed directly or can be dissolved in a liquid such as water and consumed. In addition, gel-like refers to a composition containing water and a tackifier or gelling agent and having viscosity or elasticity.

The packaging form of the composition of the present invention is not particularly limited and can be appropriately selected according to the dosage form, etc. Examples include: PTP (Press-through-package) and other bubble packaging, strip packaging, heat sealing, Aluminum bags, film packaging using plastic or synthetic resin, glass containers such as small glass bottles, and plastic containers such as ampoules, etc. [Example]

Hereinafter, the present invention will be further described in detail through examples. However, the present invention is not limited to these examples, and the present invention can adopt various aspects as long as the problems of the present invention can be solved.

＜Experiment 1 Evaluation of NO Synthetic Enzyme Gene Expression＞ In this experiment, the expression level of the nitric oxide (NO) synthesizing enzyme gene was evaluated. When NO is produced by NO synthase (eNOS) in the vascular endothelium and diffuses into the vascular smooth muscle, the muscle relaxes and the blood vessels dilate. When the expression level of the NO synthase gene increases, the amount of NO synthase increases and the amount of NO produced increases. Therefore, it is expected that the flexibility of blood vessels, the function of vascular endothelium, and the blood flow will improve. Based on the above, by evaluating the expression level of the NO synthase gene, the effects of improving blood vessel flexibility, improving vascular endothelial function, and improving blood flow can be evaluated.

(1)Tested substance As test substances, pine bark extract containing (+)-catechin, (-)-catechin, and PB3, and (-)-catechin reagent (manufactured by Nagara Scientific) and PB3 reagent (manufactured by ChemFaces) were used. ). Mix these ingredients, dissolve them in DMSO (Dimethyl sulfoxide, dimethyl sulfoxide) to achieve the ratio in Table 1, and use Endothelial Cell Growth Medium 2 (EGM-2) so that the added concentration of DMSO reaches 0.5%. The test substances of Examples and Comparative Examples were prepared by diluting with culture medium (manufactured by Lonza). In addition, (A) catechin is the total amount of (+)-catechin and (-)-catechin.

[Table 1] Comparative example 1 Example 1 Example 2 Comparative example 2 The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 0.50 0.75 10.3 20.0 (A)Catechin (μg/ml) 1.67 2.14 4.56 4.76 (B)PB3(μg/ml) 3.33 2.86 0.44 0.24 Total amount of (A) and (B) [(A) + (B)] (μg/ml) 5.00 5.00 5.00 5.00

(2) Cell culture Human umbilical cord vein endothelial cells (manufactured by Lonza) were cultured in EGM-2 medium. Inoculate the above-mentioned cells on a collagen-coated 96-well plate at 100 μL/well so that the cells reach 1×10 ⁴ cells/well, and pre-culture for 24 hours in a 37°C, 5 volume% CO ₂ incubator. After removing the medium from each well, add a medium containing the test substances in Table 1 at 100 μL/well, and culture for 24 hours.

(3) Determination of expression level of NO synthase gene After removing the culture medium from each well, the cells were washed once with PBS (phosphate buffered saline), and RNA was recovered using RNeasy Mini Kit (manufactured by QIAGEN). The obtained RNA was subjected to real-time polymerase chain reaction (Real-time PCR) using One Step TBGreen (registered trademark) PrimeScript RT-PCR KitII (manufactured by Takara). The NOS3 (eNOS) gene expression level was measured using a NOS3 (eNOS) primer (manufactured by Takara). As an endogenous control group, a GAPDH primer (manufactured by QIAGEN) was used to measure the gene expression level of GAPDH.

(4) Evaluation of NO synthase gene expression Calculate the NO synthase when the expression amount of the group (Comparative Example 2) in which the mass ratio [(A)/(B)] of the content of (A) catechin to the content of (B) PB3 is 20.0 is 1 is calculated. The relative value of gene expression. The results are shown in Figure 1.

The mass ratio [(A)/(B)] of the content of (A) catechin to the content of (B) PB3 is 0.50 (Comparative Example 1), and the content of (A) catechin relative to (B) The mass ratio of the content of PB3 [(A)/(B)] is 20.0 (Comparative Example 2). The mass ratio of (A) the content of catechin to (B) the content of PB3 ( A) A group in which the mass ratio [(A)/(B)] of catechin content to (B) PB3 content is 0.75 (Example 1), and (A) catechin content to (B) ) The mass ratio [(A)/(B)] of PB3 content was 10.3 (Example 2), which showed an increase in the expression of the NO synthase gene. Therefore, it is suggested that the composition of the present invention is obtained by ingesting a combination in which the mass ratio [(A)/(B)] of the content of (A) catechin to the content of (B) PB3 is 0.60 or more and 15 or less. The substance exerts an effect of increasing the expression level of the NO synthase gene, thereby exerting an effect of improving blood vessel flexibility, improving vascular endothelial function, and improving blood flow, and can be used as an oral composition.

＜Evaluation of Prostaglandin I2 Production in Test 2＞ In this trial, prostaglandin I2 (PGI2) production was assessed. When prostaglandin I2 is produced in the vascular endothelium and diffuses into the vascular smooth muscle, the muscle relaxes and the blood vessels dilate. By increasing the production of prostaglandin I2, it is expected that the flexibility of blood vessels, the function of vascular endothelium, the inhibition of platelet aggregation, and the improvement of blood flow can be improved. Based on the above, by evaluating the production of prostaglandin I2, it is possible to evaluate the vascular flexibility improving effect, the vascular endothelial function improving effect, the platelet aggregation inhibiting effect, and the blood flow improving effect. Since the half-life of prostaglandin I2 is short, as an evaluation of the production of prostaglandin I2, the metabolite of prostaglandin I2, 6-keto prostaglandin (6-keto Prostaglandin) F1α, is evaluated.

(1)Tested substance The test substance is prepared in the same manner as in "Test 1 (1) Test substance".

(2) Cell culture Cells were cultured in the same manner as in "Test 1 (2) Cell culture".

(3) Determination of prostaglandin I2 production The culture medium was collected from each well, and the amount of 6-ketoprostaglandin F1α in the culture medium was measured using a 6-ketoprostaglandin F1α ELISA kit (manufactured by Cayman).

(4) Assessment of prostaglandin I2 production Calculate prostaglandin I2 when the expression amount of the group (Comparative Example 2) in which the mass ratio [(A)/(B)] of the content of (A) catechin to the content of (B) PB3 is 20.0 is 1 is calculated. The relative value of the production quantity. The results are shown in Figure 2.

The mass ratio [(A)/(B)] of the content of (A) catechin to the content of (B) PB3 is 0.50 (Comparative Example 1), and the content of (A) catechin relative to (B) The mass ratio of the content of PB3 [(A)/(B)] is 20.0 (Comparative Example 2). The mass ratio of the content of (A) catechin to the content of (B) PB3 [ (A)/(B)] is 0.75 (Example 1), and the mass ratio [(A)/(B)] of the content of (A) catechin to the content of (B) PB3 is 10.3 The increase in prostaglandin I2 production was seen in the group (Example 2). Therefore, it is suggested that the composition of the present invention is obtained by ingesting a combination in which the mass ratio [(A)/(B)] of the content of (A) catechin to the content of (B) PB3 is 0.60 or more and 15 or less. It exerts the effect of increasing the production of prostaglandin I2, thereby exerting the effect of improving blood vessel flexibility, improving the function of vascular endothelium, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

(Manufacturing example) Hereinafter, based on the results of Examples, production examples of the present invention are shown.

[Manufacturing Example 1-3: Granule 1] Using the composition in Table 2, granule 1 containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 was produced. The granules described in Production Example 1-3 only need to be ingested at 3 g per day. The granules may be dissolved in 100 mL of water or other solvents and ingested, or may be ingested directly without being dissolved. The granules of Production Examples 1 to 3 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as oral compositions.

[Table 2] Granules 1 Manufacturing example 1 Manufacturing example 2 Manufacturing example 3 Pine bark extract 6.00% 10.00% 5.00% Barley young leaf powder 33.00% kale powder 3.00% Ashitaba powder 3.00% Matcha 5.00% 50.00% cocoa powder 45.00% Sucralose 0.30% maltose 25.00% 35.00% polydextrose 32.00% 20.00% 14.70% Indigestible dextrin 18.00% (A)Catechin 0.0300% 0.0500% 0.0740% (B) Proanthocyanidin B3 0.0200% 0.0350% 0.0350% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.50 1.43 2.11

[Manufacturing Example 4-6: Granules 2] Using the composition in Table 3, granule 2 containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 was produced. The granules described in Production Example 4-6 only need to be ingested at 25 g per day, and can be dissolved in 200 mL of water or the like and ingested. The granules of Production Examples 4 to 6 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as oral compositions.

[table 3] Granules 2 Manufacturing example 4 Manufacturing example 5 Manufacturing example 6 Pine bark extract 5.00% 0.30% 3.00% whey protein 75.00% 40.00% Soy Protein 60.00% 30.00% green tea extract 3.00% Sanxianjiao 5.00% 5.00% citric acid 3.00% 3.00% Sucralose 0.30% 0.30% 0.30% spices 0.30% 0.30% 0.30% Vitamin C 0.10% maltose 36.10% 21.40% polydextrose 8.30% (A)Catechin 0.0980% 0.0009% 0.0500% (B) Proanthocyanidin B3 0.0160% 0.0001% 0.0200% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 6.13 9.00 2.50

[Manufacture Example 7-9: Tablet] A tablet containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 was manufactured using the composition in Table 4. . Tablets are available with a tablet diameter of 8 mm , the thickness of the ingot is 4.5 mm, the weight is 250 mg, and the hardness is 5 kgf or above. The tablets described in Production Example 7-9 only need to be taken 1 to 2 tablets per day, and can be taken together with 100 mL of water, etc. The tablets of Production Examples 7 to 9 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as oral compositions.

[Table 4] lozenges Manufacturing example 7 Manufacturing example 8 Manufacturing example 9 Pine bark extract 20.00% 5.00% 5.00% grape seed extract 40.00% 5.00% Elastin from bonito 5.00% 5.00% green tea extract 35.00% 25.00% Reduced maltose 7.00% 27.00% 35.00% Isomalt 15.00% 10.00% 15.00% Cellulose 10.00% 15.00% 12.00% Silicon dioxide 1.00% 1.00% 1.00% calcium stearate 2.00% 2.00% Sucrose fatty acid ester 2.00% (A)Catechin 0.6000% 1.0000% 0.6100% (B) Proanthocyanidin B3 0.4000% 0.3000% 0.0800% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.50 3.33 7.63

[Manufacturing Example 10-12: Hard capsule] The content of the composition shown in Table 5 is coated with a film containing gelatin or hydroxypropyl cellulose to produce a product containing (A) catechin (containing (+)-catechin and (-)-catechin). With (B) PB3 hard capsule. Hard capsules are manufactured in 1 capsule of 300 mg. Just take 1 to 2 capsules daily, and you can take it with 100 mL of water. In addition, the hard capsules of Production Examples 10 to 12 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

[table 5] Hard capsule Manufacturing example 10 Manufacturing example 11 Manufacturing example 12 Pine bark extract 50.00% 30.00% 5.00% green tea extract 5.00% 5.00% 30.00% apple extract 10.00% 10.00% ginger extract 10.00% 5.00% 5.00% cellulose 20.00% 45.00% 55.00% Lubricant 5.00% 5.00% 5.00% (A)Catechin 0.9000% 0.6000% 0.9000% (B) Proanthocyanidin B3 0.7000% 0.4000% 0.1000% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.29 1.50 9.00

[Manufacturing Example 13-15: Soft capsule] The content of the composition shown in Table 6 is coated with a film containing gelatin to produce a product containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3. Soft capsule. Soft capsules are manufactured in 1 capsule of 300 mg. Just take 1 to 2 capsules daily, and you can take it with 100 mL of water. In addition, the soft capsules of Production Examples 13 to 15 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

[Table 6] Soft capsule Manufacturing example 13 Manufacturing example 14 Manufacturing example 15 Pine bark extract 5.00% 100% 6.00% green tea extract 5.00% hemococcin 10.00% Onion peel extract 3.00% 2.00% beeswax 10.00% 10.00% 10.00% Glyceryl fatty acid ester 0.30% 0.30% 0.30% Safflower oil 71.70% 80.70% olive oil 83.70% 1.00% (A)Catechin 0.0500% 0.0150% 0.0600% (B Proanthocyanidin B3 0.0400% 0.0045% 0.0400% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.25 3.33 1.50

[Manufacturing Example 16-18: PET beverage] Using the composition in Table 7, a PET drink containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 was produced. PET drinks are produced in 1 bottle of 500 mL. Just take 1 bottle daily. In addition, the PET drinks of Production Examples 16 to 18 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

[Table 7] PET drinks Manufacturing example 16 Manufacturing example 17 Manufacturing example 18 Pine bark extract 0.20% 0.30% 0.50% green tea 10.00% 10.00% black tea 15.00% grape seed extract 0.50% 0.50% 2.00% Vitamin C 0.05% 0.05% water remainder remainder remainder (A)Catechin 0.0050% 0.0070% 0.0080% (B) Proanthocyanidin B3 0.0040% 0.0020% 0.0060% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.25 3.50 1.33

[Manufacturing Example 19-21: Chocolate] Using the composition in Table 8, chocolate containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 was produced. A daily intake of 30 g is enough. In addition, the chocolates of Production Examples 19 to 21 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

[Table 8] chocolate Manufacturing example 19 Manufacturing example 20 Manufacturing example 21 Pine bark extract 6.0% 5.0% 1.0% Kudzu flower extract 3.0% 8.0% green tea extract 0.7% 10.0% Cocoa liquor 7.0% 7.0% 8.0% cocoa powder 3.0% 3.0% 3.0% Coco fat 20.0% vegetable oils 15.0% 20.0% All powder milk 10.0% 10.0% 10.0% granulated sugar 50.0% 51.7% 47.7% Lecithin 0.3% 0.3% 0.3% (A)Catechin 0.1800% 0.2200% 0.6500% (B) Proanthocyanidin B3 0.1400% 0.1700% 0.1200% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.29 1.29 5.42

[Manufacturing Example 22-24: Jelly] Using the composition in Table 9, a jelly containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 was produced. A daily intake of 150 g is sufficient. In addition, the jellies of Production Examples 22 to 24 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

[Table 9] jelly Manufacturing example 22 Manufacturing example 23 Manufacturing example 24 Pine bark extract 0.20% 0.10% 0.20% green tea extract 0.30% 0.10% grape seed extract 0.50% 0.10% Barnabas Leaf Extract 2.00% Indigestible dextrin 10.00% Gelatin 3.00% 2.00% Locust bean gum 3.00% Carrageenan 3.00% citric acid 5.00% granulated sugar 30.00% Sucralose 0.30% 0.30% Xiangpa 0.30% 0.30% 0.30% purified water remainder remainder remainder (A)Catechin 0.0085% 0.0058% 0.0063% (B) Proanthocyanidin B3 0.0063% 0.0056% 0.0056% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.35 1.04 1.13

[Manufacturing Example 25-27: Gummy Candy] Using the composition shown in Table 10, gummies containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 were produced. Just take 4 g daily. In addition, the gummies of Production Examples 25 to 27 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

[Table 10] gummies Manufacturing example 25 Manufacturing example 26 Manufacturing example 27 Pine bark extract 30.0% 20.0% 5.0% green tea extract 11.0% 40.0% grape seed extract 20.0% 1.0% granulated sugar 40.0% 20.0% glucose 40.0% 15.0% Gelatin 9.0% 10.0% 9.0% purified water 10.0% 10.0% 10.0% (A)Catechin 0.6800% 0.5500% 0.8500% (B) Proanthocyanidin B3 0.5800% 0.4300% 0.1800% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 1.17 1.28 4.72

[Manufacturing Example 28-30: Yogurt] Using the composition in Table 11, yogurt containing (A) catechin (containing (+)-catechin and (-)-catechin) and (B) PB3 was produced. A daily intake of 150 g is enough. Moreover, the yoghurts of Production Examples 28 to 30 are all effective in improving blood vessel flexibility, improving vascular endothelial function, inhibiting platelet aggregation, and improving blood flow, and can be used as an oral composition.

[Table 11] yogurt Manufacturing example 28 Manufacturing example 29 Manufacturing example 30 Pine bark extract 0.5% 0.3% 0.2% green tea extract 2.0% Onion peel extract 1.0% 0.6% granulated sugar 6.0% 6.0% 6.0% spices 0.3% 0.3% 0.3% yogurt 93.2% 90.4% 92.9% (A)Catechin 0.0008% 0.0075% 0.0030% (B) Proanthocyanidin B3 0.0001% 0.0023% 0.0020% The ratio of (A) catechin content to (B) PB3 content [(A)/(B)] 8.00 3.26 1.50 [Industrial availability]

The composition of the present invention exhibits excellent blood vessel flexibility improving effects, vascular endothelial function improving effects, platelet aggregation inhibiting effects, and blood flow improving effects. Therefore, it can be used as an oral composition and has high industrial applicability.

FIG. 1 is a graph showing the expression level of the NO synthase gene in Examples and Comparative Examples. Fig. 2 is a graph showing the production amount of prostaglandin I2 in Examples and Comparative Examples.

Claims (17)

A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood vessel flexibility, and The mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 or more and 15 or less. The composition of claim 1, which is a composition for improving blood vessel flexibility, and The mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 to 5.42. Use of a composition for producing a blood vessel flexibility improving agent or a food for improving blood vessel flexibility, and The above composition contains ingredients (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood vessel flexibility, The mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) is 0.60 or more and 15 or less. Such as the use of claim 3, wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the above composition is 0.60 or more and 5.42 or less. A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood flow, and The mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 or more and 15 or less. The composition of claim 5, which is a composition for improving blood flow, and The mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 to 5.42. Use of a composition for manufacturing a blood flow improving agent or a blood flow improving food, and The above composition contains (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood flow. The mass ratio of the content of component (A) to the content of component (B) in the above composition is [ (A)/(B)] is 0.60 or more and 15 or less. Such as the use of claim 7, wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the above composition is 0.60 or more and 5.42 or less. A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving vascular endothelial function, and the content of component (A) in the composition is relative to the content of component (B) The mass ratio [(A)/(B)] is between 0.60 and 15. The composition of claim 9, which is a composition for improving vascular endothelial function, and The mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 to 5.42. Use of a composition for producing a vascular endothelial function improving agent or a food for improving vascular endothelial function, and The above composition contains (A) catechin and (B) proanthocyanidin B3 as an active ingredient for improving blood flow. The mass ratio of the content of component (A) to the content of component (B) in the above composition is [ (A)/(B)] is 0.60 or more and 15 or less. Such as the use of claim 11, wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the above composition is 0.60 or more and 5.42 or less. A composition containing (A) catechin and (B) proanthocyanidin B3 as an active ingredient for inhibiting platelet aggregation, and the content of component (A) in the composition is relative to the content of component (B). The mass ratio [(A)/(B)] is 0.60 or more and 15 or less. The composition of claim 13, which is a composition for inhibiting platelet aggregation, and The mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the composition is 0.60 or more and 1.67 or less. Use of a composition for manufacturing a platelet aggregation inhibitor or a platelet aggregation inhibitor food, and The above composition contains (A) catechin and (B) proanthocyanidin B3 as an active ingredient for inhibiting platelet aggregation. The mass ratio of the content of component (A) to the content of component (B) in the above composition is [ (A)/(B)] is 0.60 or more and 15 or less. Such as the use of claim 15, wherein the mass ratio [(A)/(B)] of the content of component (A) to the content of component (B) in the above composition is 0.60 or more and 1.67 or less. An oral composition, characterized in that it contains (A) catechin and (B) proanthocyanidin B3, and the mass ratio of the content of component (A) to the content of component (B) in the composition [(A)/(B)] is 0.60 or more and 15 or less.