A composition containing procyanidin and ceramide or nucleic acid.

Abstract

To provide a composition that can improve or maintain the function of blood vessels, or improve or maintain the function of blood vessels, the properties of blood, blood flow, etc. [Solution] A composition containing procyanidin and ceramide or nucleic acid.

Description

Technical Field

[0001] The present invention relates to a composition containing procyanidin and ceramide or nucleic acid.

Background Art

[0002] With changes in diet and lifestyle, lifestyle-related diseases are increasing. Among such lifestyle-related diseases, in recent years, diseases related to blood vessels and blood, such as hypertension, angina pectoris, myocardial infarction, and cerebrovascular disorders, have been on the increase. Since such lifestyle-related diseases are chronic diseases, their prevention and treatment require a long period of time. Therefore, there is a demand for foods and beverages that can safely and effectively improve the functions of blood vessels, the properties of blood, blood flow, etc. over a long period of time. For example, as food materials that improve vascular flexibility and improve vascular endothelial function, hops and chlorogenic acid are known (see Patent Documents 1 and 2).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] An object of the present invention is to provide a composition capable of improving or maintaining the functions of blood vessels, the properties of blood, blood flow, etc.

Means for Solving the Problems

[0005] The present inventors have found that by blending ceramide or nucleic acid together with procyanidin, an excellent effect of improving or maintaining vascular flexibility, an excellent effect of improving or maintaining vascular endothelial function, an excellent effect of suppressing platelet aggregation or maintaining platelet aggregability, or an excellent effect of improving or maintaining blood flow can be obtained, and have thus completed the present invention.

[0006] In other words, the present invention is as follows: [1] A composition comprising procyanidin as an active ingredient for improving or maintaining vascular flexibility, further comprising ceramide or nucleic acid. [2] A composition comprising procyanidin as an active ingredient for improving or maintaining vascular endothelial function, further comprising ceramide or nucleic acid. [3] A composition comprising procyanidin as an active ingredient for inhibiting platelet aggregation or maintaining platelet aggregation ability, further comprising ceramide or nucleic acid. [4] A composition comprising procyanidin as an active ingredient for improving or maintaining blood flow, further comprising ceramide or nucleic acid. [5] A composition for improving or maintaining vascular flexibility, comprising procyanidin and ceramide or nucleic acid. [6] A composition for improving or maintaining vascular endothelial function, comprising procyanidin and ceramide or nucleic acid. [7] A composition for inhibiting or maintaining platelet aggregation, comprising procyanidin and ceramide or nucleic acid. [8] A composition for improving or maintaining blood flow, comprising procyanidin and ceramide or nucleic acid. [9] The composition according to [1] to [8], characterized in that the procyanidin is pine bark extract. [Effects of the Invention]

[0007] The composition of the present invention exhibits at least one of the following effects: improvement or maintenance of vascular flexibility, improvement or maintenance of vascular endothelial function, inhibition of platelet aggregation or maintenance of platelet aggregation ability, and improvement or maintenance of blood flow. [Brief explanation of the drawing]

[0008] [Figure 1] This figure shows the relative expression levels of the NO synthase gene in the compositions of the present invention (procyanidin + ceramide, procyanidin + nucleic acid). [Figure 2]This figure shows the amount of prostaglandin I2 produced (relative value) by the composition of the present invention (procyanidin + ceramide). [Figure 3] This figure shows the amount of prostaglandin I2 produced (relative value) by the composition of the present invention (procyanidin + nucleic acid). [Modes for carrying out the invention]

[0009] The composition of the present invention is characterized by containing procyanidin and ceramide or nucleic acid. The composition of the present invention may also contain all three: procyanidin, ceramide, and nucleic acid.

[0010] The composition of the present invention exhibits at least one of the following effects: improvement or maintenance of vascular flexibility, improvement or maintenance of vascular endothelial function, inhibition or maintenance of platelet aggregation, and improvement of blood flow, with procyanidin being the active ingredient for these effects. Because the composition of the present invention exhibits these effects, it can be used as a composition for improving or maintaining vascular flexibility, a composition for improving or maintaining vascular endothelial function, a composition for inhibiting or maintaining platelet aggregation, or a composition for improving or maintaining blood flow.

[0011] Here, "improvement or maintenance" in this invention is a concept that includes suppressing, maintaining, and enhancing the decline of properties and functions. Specifically, improving or maintaining vascular flexibility includes suppressing, maintaining, and enhancing the decline of vascular flexibility. Improving or maintaining vascular endothelial function includes suppressing, maintaining, and enhancing the decline of vascular endothelial function. Improving or maintaining blood flow includes suppressing, maintaining, and enhancing the decline of blood flow.

[0012] The following describes each component included in the composition of the present invention. [Procyanidins] Procyanidins are a group of compounds consisting of condensate polymers with a degree of polymerization of 2 or more, with flavan-3-ol as the basic structural unit. It is preferable that the proanthocyanidins contain condensate polymers with a degree of polymerization of 2 or more. In particular, proanthocyanidins containing a large amount of condensate polymers with a low degree of polymerization are preferred. Examples of condensate polymers with a low degree of polymerization include condensate polymers with a degree of polymerization of 2 to 30 (2 to 30-mers), and condensate polymers with a degree of polymerization of 2 to 10 (2 to 10-mers) are preferred, and condensate polymers with a degree of polymerization of 2 to 4 (2 to 4-mers) are particularly preferred, as they can provide a higher effect. Among the condensate polymers with a degree of polymerization of 2 to 4 (2 to 4-mers), it is preferable that they contain procyanidin B1 and procyanidin B3. Procyanidin B1 is a dimer in which (-)epicatechin and (+)catechin are linked by a C4-C8 bond, and procyanidin B3 is a dimer in which (+)catechin and (+)catechin are linked by a C4-C8 bond.

[0013] Procyanidins are components found in pine bark (the bark of the Pinus genus in the Pinaceae family), as well as in apples, grapes, and other plants. The procyanidins contained in the composition of the present invention may be purified from plants, chemically synthesized, or commercially available reagents, or plants containing procyanidins may be used. When using plants containing procyanidins as the procyanidins contained in the composition of the present invention, it is preferable to use pine bark in order to obtain a higher effect.

[0014] Examples of pine trees used as raw materials for pine bark include, but are not limited to, French maritime pine (Pinus pinaster), larch, Japanese black pine, Japanese red pine, Japanese white pine, Japanese white pine, Korean pine, Japanese stone pine, Ryukyu pine, Japanese white pine, Japanese pine, and Japanese white pine. Among these, French maritime pine is preferred because it can produce a higher effect.

[0015] In the present invention, pine bark can be processed and used. Examples of processed pine bark include chip-like substances, crushed materials, squeezed juices, extracts, and dried powders thereof. Considering the pharmaceutical properties, the pine bark used in the present invention is preferably a crushed material, squeezed juice, extract, or dried powder thereof because it is easy to apply. From the viewpoint of obtaining higher effects, an extract or its dried powder is more preferable. The processed pine bark may be manufactured by a method commonly known to those skilled in the art or may be a product commercially available. For example, a pine bark extract manufactured by Toyo Shinyaku Co., Ltd. can be used.

[0016] Examples of the extraction solvent used for obtaining the pine bark extract include water, organic solvents, and water-containing organic solvents (water-containing alcohols such as water-containing ethanol). Examples of organic solvents include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane, cyclohexane, propylene glycol, water-containing ethanol, water-containing propylene glycol, ethyl methyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible oils and fats, 1,1,1,2-tetrafluoroethane, and 1,1,2-trichloroethene. These water and organic solvents may be used alone or in combination. It is preferable to use water as the extraction solvent. The temperature of the solvent during extraction is not limited as long as it is below the boiling point of the solvent used.

[0017] There is no particular limitation on the method for obtaining the pine bark extract. For example, a heating extraction method, a supercritical fluid extraction method, a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method, etc. can be mentioned. Also, a plurality of extraction methods may be combined. By combining a plurality of extraction methods, it becomes possible to obtain pine bark extracts with various compositions.

[0018] Supercritical fluid extraction is a method of extraction that uses a supercritical fluid, which is a fluid that has exceeded the critical point (critical temperature, critical pressure) of the substance's gaseous or liquid state. Examples of supercritical fluids include carbon dioxide, ethylene, propane, and nitrous oxide (laughing gas), but carbon dioxide is preferred.

[0019] In supercritical fluid extraction, an extraction step is performed to extract the target component using a supercritical fluid, and a separation step is performed to separate the target component from the supercritical fluid. In the separation step, any of the following methods may be used: extraction and separation by pressure change, extraction and separation by temperature change, or extraction and separation using adsorbents or absorbents.

[0020] Alternatively, supercritical fluid extraction may be performed using the entrainer addition method. In this method, approximately 2-20 w / v% of substances such as ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to the extraction fluid, and supercritical fluid extraction is performed using this fluid. This method dramatically increases the solubility of the target extract, such as procyanidin B1, procyanidin B3, or catechins, in the extraction solvent, or enhances the selectivity of separation, making it an efficient method for obtaining pine bark extract.

[0021] Supercritical fluid extraction has several advantages: it can be operated at relatively low temperatures, making it applicable to substances that denature or decompose at high temperatures; no extraction fluid remains; and the solvent can be recycled, eliminating the need for desolvation steps and simplifying the process.

[0022] For safety reasons, it is preferable to purify the pine bark extract obtained by the above extraction method using a column method or a batch method. Examples of column methods include purification using adsorbent carriers such as Diaion HP-20, Sephadex-LH20, and chitin.

[0023] The amount of procyanidin in the composition of the present invention can be analyzed by HPLC. For example, it can be measured using an HPLC analyzer equipped with a UV absorption detector. The analytical column used is an L-Column ODS 3μm (4.6 × 250 mm) manufactured by the Chemicals Evaluation and Research Institute of Japan. The mobile phases are 0.1 M aqueous acetic acid solution (mobile phase A) and 0.1 M acetonitrile acetate solution (mobile phase B). The column temperature can be 40°C and the flow rate 1.0 mL / min. The gradient conditions can be as follows.

[0024] [Table 1]

[0025] [Ceramide] In this invention, the ceramides used may include human-type ceramides such as ceramide 1, ceramide 2, and ceramide 3, as well as animal-derived ceramides extracted from the brains and spinal cords of animals such as cattle, horses, and pigs, and plant-derived ceramides extracted from wheat, rice, soybeans, spinach, corn, konjac, pineapple, etc. Furthermore, the ceramides used in this invention may also be glycoceramides, specifically those with monosaccharides such as galactosylceramide and glucosylceramide attached, or those with oligosaccharides attached.

[0026] In the composition of the present invention, it is preferable to use plant-derived ceramides, and it is even more preferable to use glucosylceramides derived from grasses such as wheat, corn, and rice. Among these, it is particularly preferable to use glucosylceramide extracted from rice, which is obtained from rice, as this can yield a higher effect. Examples of solvents used for extraction include water; lower alcohols such as ethanol, methanol, isopropanol, and butanol; lower esters such as ethyl acetate and methyl acetate; acetone; and mixed solvents of these with water. Ethanol or aqueous ethanol is preferred because it can efficiently extract the active ingredients. The temperature of the extraction solvent can be appropriately set between room temperature and below the boiling point, depending on the solvent used.

[0027] The amount of ceramide in the composition of the present invention can be analyzed by liquid chromatography. For example, it can be measured using a high-performance liquid chromatograph (HPLC-ELSD) with a light scattering detector. The analytical column can be an Inertsil Sil 100-5 (4.6 × 150 mm) manufactured by GL Sciences, and the mobile phase can be a liquid medium consisting of chloroform (mobile phase A) and a 95% by volume methanol solution (mobile phase B). The column temperature can be 35°C and the flow rate 1 mL / min. The gradient conditions can be as follows.

[0028] [Table 2]

[0029] [Nucleic acid] In the present invention, either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) may be used as the nucleic acid. It is preferable to use ribonucleic acid (RNA) because it can be used to obtain a higher effect. Specifically, examples of nucleic acids used in the present invention include nucleic acids extracted from yeast and high molecular weight nucleic acids purified from salmon milt.

[0030] The compositions of the present invention can be used, for example, as pharmaceuticals (including quasi-drugs), functional foods such as foods for specified health uses, foods with nutritional function claims, and foods with functional claims, which have been approved by designated institutions, and other so-called health foods.

[0031] The compositions of the present invention can be used as at least one of the following: compositions for improving or maintaining vascular flexibility, compositions for improving or maintaining vascular endothelial function, compositions for inhibiting or maintaining platelet aggregation, and compositions for improving or maintaining blood flow. Such compositions for improving or maintaining vascular flexibility, compositions for improving or maintaining vascular endothelial function, compositions for inhibiting or maintaining platelet aggregation, and compositions for improving or maintaining blood flow contain procyanidin and ceramide or nucleic acid, and are not particularly limited as long as they can be distinguished from other products in that they exhibit the functions of improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, respectively. For example, the scope of the present invention includes products in which the functions of improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow are displayed on the product itself, packaging, instruction manual, or promotional materials (advertising media).

[0032] The composition of the present invention may, but is not limited to, a composition in which procyanidin is listed as the active ingredient. For example, it may not list any active ingredients. Furthermore, even general foods that are manufactured and sold with a suggested function or use are included within the scope of the present invention. For example, this includes foods that are sold with testimonials from people who have consumed them, mentioning their function or use, posted on websites, etc.

[0033] Specifically, in the case of so-called health foods, examples of compositions for improving or maintaining vascular flexibility include those that display phrases such as "Helps maintain the flexibility of blood vessels that decline with age," "Increases the degree of vascular dilation after constricting blood vessels," "Maintains the degree of vascular dilation after constricting blood vessels," "Increases vascular flexibility," "Maintains vascular flexibility," "Increases the suppleness of blood vessels," "Maintains the suppleness of blood vessels," "Enhances vascular function," and "Maintains vascular function." Examples of compositions for improving or maintaining vascular endothelial function include those that display phrases such as "Enhances vascular endothelial function," "Maintains vascular endothelial function," "Enhances the vascular endothelial function of arteries that decline with age," "Maintains the vascular endothelial function of arteries that decline with age," "Enhances vascular function," and "Maintains vascular function." Furthermore, examples of compositions for inhibiting or maintaining platelet aggregation include those that display phrases such as "Inhibits platelet aggregation," "Prevents platelet aggregation," "Maintains platelet aggregation," "Helps maintain blood fluidity," "Helps maintain blood fluidity (platelet aggregation ability)," and "Helps maintain blood flowability (platelet aggregation ability)." Furthermore, examples of compositions for improving or maintaining blood flow may include those that display phrases such as "helps maintain blood fluidity," "helps maintain ease of blood flow," "improves blood flow," "maintains blood flow," "maintains healthy blood flow," "maintains healthy peripheral blood flow," "increases and restores reduced peripheral blood flow to normal," "regulates reduced blood flow to normal," "regulates reduced peripheral blood flow to normal," "improves blood circulation," "improves coldness," "for those concerned about swelling," "for those concerned about skin color," "for those concerned about dark circles under the eyes," "for supporting male function," and "for male vitality."

[0034] The form of the composition of the present invention is not particularly limited and can be any form. For example, forms suitable for oral use include powder, granules, tablets, liquid, gel, paste, capsules such as hard capsules and soft capsules, caplets, tablets, gels, jellies, gummies, wafers, biscuits, cookies, cakes, chewables, syrups, and sticks. In addition, various excipients, binders, lubricants, stabilizers, diluents, fillers, thickeners, gelling agents, emulsifiers, colorants, flavorings, sweeteners, and additives can be added depending on the form used.

[0035] The composition of the present invention is preferably in granular, tablet, capsule, or liquid form, and more preferably in granular, tablet, or capsule form, because it is easy to ingest. Here, "granular form" refers to a powder that has been granulated, and may be consumed directly or dissolved in a liquid such as water. "Gel form" refers to a state in which water and a gelling agent are contained and have viscosity or elasticity.

[0036] The amount of procyanidins in the composition of the present invention may be appropriately included within a range that achieves its effect. For example, the composition of the present invention may contain 0.00001 to 30% by mass of procyanidins on a dry matter basis, preferably 0.0001 to 20% by mass, and more preferably 0.001 to 10% by mass.

[0037] The ceramide content in the composition of the present invention may be appropriately included within a range that achieves its effect. For example, the composition of the present invention may contain 0.00001 to 30% by mass of ceramide on a dry matter basis, preferably 0.0001 to 20% by mass, and more preferably 0.001 to 10% by mass.

[0038] The nucleic acid content in the composition of the present invention may be appropriately included within a range that achieves its effect. For example, the composition of the present invention can contain 0.00001 to 30% by mass of nucleic acid on a dry matter basis, preferably 0.0001 to 20% by mass, and more preferably 0.001 to 10% by mass.

[0039] The preferred mass ratio of procyanidin to ceramide is, for example, 1:0.0000003 to 3000000, preferably 1:0.000005 to 200000, and more preferably 1:0.0001 to 10000. Similarly, the preferred mass ratio of procyanidin to nucleic acid is, for example, 1:0.0000003 to 3000000, preferably 1:0.000005 to 200000, and more preferably 1:0.0001 to 10000. These mass ratios allow for a higher efficacy to be obtained.

[0040] The content of procyanidin and ceramide and / or nucleic acids in the composition of the present invention may be appropriately included within a range that produces the desired effect. For example, the composition of the present invention may contain 0.00003 to 90% by mass on a dry matter basis, preferably 0.0003 to 60% by mass, and more preferably 0.003 to 30% by mass.

[0041] There are no particular restrictions on the amount of the composition used in the present invention to be ingested. However, in order to obtain a higher effect, it is preferable that the amount of procyanidin ingested by an adult is 0.1 mg or more per day, more preferably 1 mg or more, and even more preferably 2 mg or more. The upper limit is, for example, 100 mg, preferably 50 mg, and more preferably 20 mg.

[0042] The composition of the present invention can be appropriately designed so that the daily intake of procyanidin is the above intake amount, and it may be consumed in one dose or in multiple doses. That is, for example, it can be contained in one container or divided into two to four containers to represent one day's supply. Furthermore, the daily intake of the composition of the present invention is preferably 0.05 to 50 g, more preferably 0.1 to 10 g, and even more preferably 0.2 to 5 g, when the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.). Furthermore, when the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), it is preferably 10 to 1500 g, more preferably 30 to 1000 g, and even more preferably 50 to 750 g.

[0043] The compositions of the present invention can be prepared by known methods, with the addition of other components besides procyanidins, ceramides, and nucleic acids, as needed. [Examples]

[0044] The present invention will be described in more detail below based on examples, but the present invention is not limited thereto.

[0045] <Test 1: Evaluation of NO synthase gene expression levels> We evaluated the expression level of the nitric oxide (NO) synthase gene. When NO produced by NO synthase (eNOS) in the vascular endothelium diffuses to the vascular smooth muscle, the muscle relaxes and the blood vessels dilate. An increase in NO synthase gene expression leads to an increase in NO synthase levels and thus an increase in NO production, which can be expected to improve or maintain vascular flexibility, improve or maintain vascular endothelial function, and improve or maintain blood flow. Based on the above, by evaluating the NO synthase gene expression level, it is possible to assess the effects of improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, and improving or maintaining blood flow.

[0046] [Test substance] The following were used: a hot water extract of French maritime pine bark containing procyanidin B1 and procyanidin B3 as procyanidins (containing 3.84% procyanidins); rice-derived glucosylceramide as ceramide; and Torula yeast-derived ribonucleic acid (RNA) as nucleic acid. All were commercially available products.

[0047] The test substances for Examples 1 and 2 and Comparative Examples 1 to 3 were prepared by dissolving the substances in DMSO in the proportions shown in Table 3 below, and then diluting them in Endothelial Cell Growth Medium 2 (EGM-2) (manufactured by Lonza) to an additive concentration of 0.5% DMSO.

[0048] [Table 3]

[0049] [Cell culture] Human umbilical vein endothelial cells (HUVEC: Lonza) were cultured in EGM-2 medium. The cells were placed in 1 × 10⁶ wells of a collagen-coated 96-well plate. 4 Cells were seeded at a concentration of 100 μL / well to achieve a cell / well ratio, and pre-cultured for 24 hours in a 37°C, 5V %CO2 incubator. After removing the culture medium from each well, 100 μL / well of the culture medium containing the test substance shown in Table 3 was added, and the cells were cultured for 24 hours.

[0050] [Measurement of NO synthase gene expression level] After removing the culture medium from each well, the wells were washed once with PBS, and RNA was recovered using the RNeasy Mini Kit (QIAGEN). Real-time PCR was performed on the obtained RNA using the One Step TBGreen® PrimeScript RT-PCR Kit II (Takara). The gene expression level of NOS3 (eNOS) was measured using a NOS3 (eNOS) primer (Takara). As an endogenous control, the gene expression level of GAPDH was measured using a GAPDH primer (QIAGEN).

[0051] [Evaluation of NO synthase gene expression levels] The relative expression levels of the NO synthase gene were calculated, with the expression level of the group administered only pine bark extract (Comparative Example 1) set to 1. The results are shown in Figure 1.

[0052] As shown in Figure 1, the group administered pine bark extract and ceramide (Example 1) showed a significant increase in NO synthase gene expression compared to the group administered pine bark extract alone (Comparative Example 1) and the group administered ceramide alone (Comparative Example 2). Furthermore, the group administered pine bark extract and nucleic acid (Example 2) also showed a significant increase in NO synthase gene expression compared to the group administered pine bark extract alone (Comparative Example 1) and the group administered nucleic acid alone (Comparative Example 3). Based on the above, a significant increase in NO synthase gene expression is observed when procyanidin is combined with ceramide or nucleic acid, resulting in excellent improvement or maintenance of vascular flexibility, excellent improvement or maintenance of vascular endothelial function, and excellent improvement or maintenance of blood flow.

[0053] <Test 2: Evaluation of Prostaglandin I2 Production> We evaluated the amount of prostaglandin I2 (PGI2) produced. When prostaglandin I2 is produced in the vascular endothelium and diffuses to the vascular smooth muscle, the muscle relaxes and the blood vessels dilate. Prostaglandin I2 also has an inhibitory effect on platelet aggregation. An increase in prostaglandin I2 production can be expected to improve or maintain vascular flexibility, improve or maintain vascular endothelial function, inhibit or maintain platelet aggregation ability, and improve or maintain blood flow. Therefore, by evaluating the amount of prostaglandin I2 produced, it is possible to evaluate the effects of improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow. Because prostaglandin I2 has a short half-life, 6-ketoprostaglandin F, a metabolite of prostaglandin I2, can be used to evaluate the amount of prostaglandin I2 produced. 1α I evaluated it.

[0054] [Test substance] The test substances were prepared using the same method as in Test 1, as shown in Tables 4 and 5.

[0055] [Table 4]

[0056] [Table 5]

[0057] [Cell culture] Cell culture was performed using the same method as in Experiment 1.

[0058] [Measurement of prostaglandin I2 production] The culture medium was collected from each well, and the 6-keto prostaglandin F1α ELISA kit (Cayman) was used to elucidate the 6-keto prostaglandin F1α in the culture medium. 1α The amount was measured, and the amount of prostaglandin I2 produced was evaluated.

[0059] [Evaluation of prostaglandin I2 production] In the test groups shown in Table 4, the relative values ​​of prostaglandin I2 production were calculated, with the expression level of the group administered only pine bark extract at 1 μg / ml (Comparative Example 4) set to 1. The results are shown in Figure 2.

[0060] Furthermore, in the test groups shown in Table 5, the relative values ​​of prostaglandin I2 production were calculated, with the expression level of the group administered only pine bark extract at 10 μg / ml (Comparative Example 6) set to 1. The results are shown in Figure 3.

[0061] As shown in Figure 2, the group administered pine bark extract and ceramide (Example 3) showed an increase in prostaglandin I2 production compared to the group administered pine bark extract alone (Comparative Example 4) and the group administered ceramide alone (Comparative Example 5). Therefore, since the combination of procyanidin and ceramide increases prostaglandin I2 production, it is possible to obtain excellent effects on improving or maintaining vascular flexibility, excellent effects on improving or maintaining vascular endothelial function, excellent effects on inhibiting or maintaining platelet aggregation, and excellent effects on improving or maintaining blood flow.

[0062] Furthermore, as shown in Figure 3, the group administered pine bark extract and nucleic acid (Example 4) showed an increase in prostaglandin I2 production compared to the group administered pine bark extract alone (Comparative Example 6) and the group administered nucleic acid alone (Comparative Example 7). Therefore, since the combination of procyanidin and nucleic acid increases prostaglandin I2 production, it is possible to obtain excellent effects on improving or maintaining vascular flexibility, excellent effects on improving or maintaining vascular endothelial function, excellent effects on inhibiting or maintaining platelet aggregation, and excellent effects on improving or maintaining blood flow.

[0063] [Manufacturing Examples 1-3] (Manufacturing of Granules) Granules containing procyanidin and ceramide or nucleic acid were prepared according to the formulations shown in Table 6. The granules described in Production Examples 1-3 only require a daily intake of 3 g and may be taken dissolved in 100 ml of water or other solvent, or taken as is without dissolving. All of the granules in Production Examples 1-3 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, and are useful as oral compositions.

[0064] [Table 6]

[0065] [Manufacturing Example 4-6] (Manufacturing of Granules) Granules containing procyanidin and ceramide or nucleic acid were prepared according to the formulations shown in Table 7. The granules described in Production Examples 4-6 only require a daily intake of 25 g and can be dissolved in 200 ml of water or other liquid before ingestion. All of the granules in Production Examples 4-6 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, and are useful as oral compositions.

[0066] [Table 7]

[0067] [Manufacturing Example 7-9: Tablets] Tablets containing procyanidin and ceramide or nucleic acid were manufactured according to the formulations shown in Table 8. The tablets were manufactured with a diameter of 8 mmφ, a thickness of 4.5 mm, a weight of 250 mg, and a hardness of 5 kgf or more. The tablets described in Manufacturing Examples 7-9 only need to be taken 1 to 4 times per day and can be taken with 100 ml of water or other liquid. All of the tablets in Manufacturing Examples 7-9 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, and are useful as oral compositions.

[0068] [Table 8]

[0069] [Manufacturing Example 10-12: Hard Capsules] Hard capsules containing procyanidin and ceramide or nucleic acid were manufactured by encapsulating the contents of the formulations shown in Table 9 with a coating containing gelatin or hydroxypropyl cellulose. Each hard capsule was manufactured to contain 300 mg. It is sufficient to take 1 to 4 capsules per day, which can be taken with 100 ml of water or other liquid. Furthermore, all of the hard capsules in Manufacturing Examples 10-12 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, making them useful as oral compositions.

[0070] [Table 9]

[0071] [Manufacturing Example 13-15: Soft Capsules] Soft capsules containing procyanidin and ceramide or nucleic acid were manufactured by encapsulating the contents of the formulations shown in Table 10 with a gelatin-containing coating. Each soft capsule was manufactured to contain 300 mg. It is sufficient to take 1 to 4 capsules per day, and they can be taken with 100 ml of water or other liquid. Furthermore, all of the soft capsules from Manufacturing Examples 13-15 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, and are useful as oral compositions.

[0072] [Table 10]

[0073] [Manufacturing example 16-18: PET beverage] PET beverages containing procyanidin and ceramide or nucleic acid were manufactured according to the formulations shown in Table 11. Each PET beverage was manufactured in a 500ml bottle. One bottle per day is sufficient. Furthermore, all of the PET beverages in manufacturing examples 16-18 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, and are useful as oral compositions.

[0074] [Table 11]

[0075] [Production Example 19-21: Chocolate] Chocolate containing procyanidin and ceramide or nucleic acid was prepared using the formulations shown in Table 12. A daily intake of 30g is recommended. Furthermore, all of the chocolates in Production Examples 19-21 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, making them useful as oral compositions.

[0076] [Table 12]

[0077] [Manufacturing Example 22-24: Jelly] A jelly containing procyanidin and ceramide or nucleic acid was prepared using the formulations shown in Table 13. A daily intake of 150g is recommended. Furthermore, all of the jellies in Production Examples 22-24 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, making them useful as oral compositions.

[0078] [Table 13]

[0079] [Manufacturing Examples 25-27: Gummy Candy] Gummies containing procyanidin and ceramide or nucleic acid were manufactured using the formulations shown in Table 14. A daily intake of 4g is recommended. Furthermore, all of the gummies in Manufacturing Examples 25-27 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, making them useful as oral compositions.

[0080] [Table 14]

[0081] [Production Example 28-30: Yogurt] Yogurt containing procyanidin and ceramide or nucleic acid was prepared using the formulations shown in Table 15. A daily intake of 150g is recommended. Furthermore, all of the yogurts in Production Examples 28-30 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting or maintaining platelet aggregation, and improving or maintaining blood flow, making them useful as oral compositions.

[0082] [Table 15] [Industrial applicability]

[0083] The composition of the present invention is industrially useful because it can improve or maintain vascular function, blood properties, blood flow, etc., and can be used as a health food or the like.

Claims

1. A composition for improving or maintaining vascular flexibility, comprising procyanidin as an active ingredient and further containing nucleic acids.

2. A composition for improving or maintaining vascular endothelial function, comprising procyanidin as an active ingredient and further containing nucleic acids.

3. A composition for inhibiting or maintaining platelet aggregation, comprising procyanidin as an active ingredient and further containing nucleic acids.

4. A composition for improving or maintaining blood flow, comprising procyanidin as an active ingredient and further containing nucleic acids.

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