JP2020196770A - Blood flow improver - Google Patents

Abstract

To provide a blood flow improver having high blood flow improvement effect.SOLUTION: A blood flow improver contains pine bark extract, and at least one selected from fructo oligosaccharide, isomaltooligosaccharide, inositol, gallic acid, iron, magnesium, and Piper longum.SELECTED DRAWING: Figure 1

Description

The present invention relates to a blood flow improving agent, and more particularly to a blood flow improving agent containing a pine bark extract and a specific other component as an active ingredient.

In modern society, disorders of blood circulation (blood flow) are often a problem due to various factors such as lack of exercise and autonomic imbalance due to stress. This disorder of blood flow (decrease in blood flow) causes various symptoms such as headache, stiff shoulders, dull skin, poor circulation, and swelling. Therefore, from the viewpoint of health and beauty, blood flow is increased and blood is increased. Measures to improve the flow are required.

Examples of the composition for improving blood flow include a hissop extract (see Patent Document 1), a composition containing a cassis concentrate and an amino acid or an organic acid (see Patent Document 2), and a chamomile extract (see Patent Document 2). (See Patent Document 3) and the like have been proposed.

On the other hand, the applicant has proposed a composition for improving blood flow (see Patent Document 4) containing a pine bark extract and a black pepper extract.

Japanese Unexamined Patent Publication No. 2006-8575 Japanese Unexamined Patent Publication No. 2004-262878 Japanese Unexamined Patent Publication No. 2005-68069 Japanese Unexamined Patent Publication No. 2012-051833

An object of the present invention is to provide a blood flow improving agent having a high blood flow improving effect.

The present inventors have diligently investigated and studied the blood flow improving ability of the pine bark extract, and found that a high blood flow improving effect can be obtained by combining the pine bark extract with a specific other component. , The present invention has been completed. That is, it was found that the blood flow improving ability can be synergistically improved by combining the pine bark extract with a specific other component having little or small blood flow improving ability.

That is, the present invention relates to a blood flow improving agent, which comprises a pine bark extract and at least one component selected from the group consisting of the following (a) to (e) as an active ingredient.
(A) At least one plant material selected from long-lived grass, black ginger, coconut palm, ginger, and hihatsu (b) At least one selected from maltose, fructo-oligosaccharide, trehalose, reduced palatinose, reduced maltose, and isoleucine. (C) At least one amino acid selected from asparagine, aspartic acid, cysteine, glutamine, isoleucine, leucine, lysine, proline, and tryptophan (d) At least one polyphenol selected from maltose and chlorogenic acid ( e) At least one vitamin / mineral selected from vitamin C, niacin, folic acid, inositol, zinc, iron, and magnesium.

..
The blood flow improving agent of the present invention may be obtained by adding an active ingredient consisting of a pine bark extract and at least one ingredient selected from the group consisting of (a) to (e).

In the blood flow improving agent of the present invention, the compounding mass ratio of the pine bark extract and other active ingredients is preferably in the range of 0.5: 1 to 70: 1.
Further, the blood flow improving agent of the present invention is preferably a tablet, a capsule, a powder, a granule, or a liquid.

The present invention also relates to a blood flow improving method (excluding medical practice), which comprises ingesting the blood flow improving agent of the present invention.

According to the blood flow improving agent of the present invention, the blood flow rate can be increased and a high blood flow improving effect can be obtained.

It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + plant material) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The upper left graph uses long-lived grass as the plant material, the upper right graph uses black ginger as the plant material, and the lower left graph uses coconut (coconut) as the plant material. The graph on the lower right shows the use of ginger as a plant material. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + plant material) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC), and is the thing which used the long pepper as a plant material. is there. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + sweetener) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The upper left graph is for maltose as a sweetener, the upper right graph is for fructooligosaccharide as a sweetener, and the lower left graph is for trehalose as a sweetener, right. The graph below shows the use of reduced palatinose as a sweetener. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + sweetener) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The graph on the left shows the use of reduced maltose as a sweetener, and the graph on the right shows the use of isomaltooligosaccharide as a sweetener. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + amino acid) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The upper left graph is for using asparagine as an amino acid, the upper right graph is for using aspartic acid as an amino acid, the lower left graph is for using cysteine as an amino acid, and the lower right graph is for using cysteine. However, glutamine is used as an amino acid. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + amino acid) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The upper left graph is for using isoleucine as an amino acid, the upper right graph is for using leucine as an amino acid, and the lower left graph is for using lysine (lysine-hydrochloride) as an amino acid. , The lower right graph shows the use of proline as an amino acid. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + amino acid) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC), and is the one using tryptophan as an amino acid. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + polyphenol) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The graph on the left shows the use of gallic acid as the polyphenol, and the graph on the right shows the use of chlorogenic acid as the polyphenol. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + vitamins, minerals) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The upper left graph is for vitamin C as vitamins, the upper right graph is for niacin as vitamins, and the lower left graph is for folic acid as vitamins, right. The graph below shows the use of inositol as a vitamin. It is a figure which shows the result of the NO production amount at the time of applying the blood flow improving agent (pine bark extract + vitamins, minerals) of this invention to a porcine pulmonary artery vascular endothelial cell (PPAEC). The upper left graph is for zinc as a mineral, the upper right graph is for iron as a mineral, and the lower left graph is for magnesium as a mineral.

The blood flow improving agent of the present invention contains a pine bark extract and at least one component (hereinafter, may be referred to as another component) selected from the group consisting of the following (a) to (e) as an active ingredient. It is characterized by doing. The blood flow improving agent of the present invention can more effectively relax the muscles around the blood vessels, dilate the blood vessels, and increase the blood flow by the synergistic effect of the combination of the active ingredients, such as headache, stiff shoulders, and so on. It is possible to effectively prevent or improve symptoms such as dullness of the skin and poor circulation.

[Pine bark extract]
The pine bark extract, which is the active ingredient of the blood flow improving agent of the present invention, contains proanthocyanidins as one of the main components. Proanthocyanidins are a group of compounds comprising flavan-3-ols and / or flavan-3,4-diols as constituent units and having a degree of polymerization of 2 or more.

Examples of the raw material of the pine bark extract used in the present invention include French coastal pine (Pinus Martima), Karamatsu, Black pine, Japanese red pine, Himekomatsu, Pinus parviflora, Japanese red pine, High pine, Ryukyu pine, Utsukushi pine, Longleaf pine, White pine and the like. Of these, French coastal pine is preferable. The obtained extract may be concentrated or dried as required to be liquid, paste-like, or powder. As the pine bark extract, a commercially available product can be used. For example, a pine bark extract manufactured by Toyo Shinyaku Co., Ltd. can be used.

Further, the pine bark extract used in the present invention preferably contains a reduced polymer having a degree of polymerization of 2 or more as proanthocyanidin. In particular, proanthocyanidins containing a large amount of a reduced polymer having a low degree of polymerization are preferable. Examples of the reduced polymer having a low degree of polymerization include a reduced polymer having a degree of polymerization of 2 to 30 (2 to 30-mer) and a polymer having a degree of polymerization of 2 to 10 (2 to 10-mer). Preferably, a reduced polymer having a degree of polymerization of 2 to 4 (2 to tetramer) is more preferable. In the present specification, a polymer having a degree of polymerization of 2 to 4 is referred to as OPC (oligomeric procyanidin). The pine bark extract used in the present invention preferably contains 20% by mass or more of OPC, more preferably 30% by mass or more, and further preferably 40% by mass or more.

The pine bark extract is obtained by extracting the pine bark with water or an organic solvent. When water is used, hot water or hot water is preferably used. Examples of the organic solvent used for extraction include foods or chemicals such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane, cyclohexane, propylene glycol, hydrous ethanol, and hydrous propylene glycol. An organic solvent that is acceptable for the production of is preferably used. These water and organic solvents may be used alone or in combination of two or more kinds of solvents. In particular, water, ethanol, hydrous ethanol and the like are preferably used.

The method for extracting the pine bark extract from the pine bark is not particularly limited, and for example, an extraction method such as a heating extraction method or a supercritical fluid extraction method can be used. In the extraction method of the pine bark extract, a plurality of extraction methods may be combined.

[Other ingredients]
(A) Plant material In the blood flow improving agent of the present invention, at least one plant material selected from long-lived grass, black ginger, coconut, ginger, and long pepper may be used together with the pine bark extract as an active ingredient. preferable.

These plant materials may be any part of the plant such as leaves, stems, roots, flowers, fruits, trunks, branches, etc. In addition to the plant materials themselves (including dried products), crushed products and juices thereof. , Plant material processed products such as extracts can be used. Examples of the pulverized product include powders and granules. The juice or extract may be liquid, but can also be used as a paste or dry powder. The extract can be obtained by extracting with an appropriate solvent, and as the solvent, for example, water (hot water, hot water), ethanol, or hydrous ethanol can be used. Commercially available plants can be used as these plant materials.

Longevity grass is a perennial plant that belongs to the genus Peucedanum of the Umbelliferae family and is also called Button Siler. Leaves and roots are preferable as the site used as the plant material of the present invention.

The scientific name of Kaempferia Parviflora is Kaempferia Parviflora, and it is a plant of the genus Kaempferia of the family Zingiberaceae that grows naturally in Southeast Asia. Rhizome is preferable as the site used as the plant material of the present invention.

Coconut is a plant of the palm family, and fruits (endosperm) are preferable as the site used as the plant material of the present invention.

Zingiber is a plant of the genus Zingiber in the family Zingiberaceae, and examples thereof include Sanshu ginger, yellow ginger, Kintoki ginger, and Tananaka ginger. Rhizome is preferable as the site used as the plant material of the present invention.

Long pepper is a plant of the Piperaceae family, and fruits are preferable as the site used as the plant material of the present invention.

(B) Sweetener In the blood flow improving agent of the present invention, at least one sweetener selected from maltose, fructooligosaccharide, trehalose, reduced palatinose, reduced maltulose, and isomaltoligosaccharide as active ingredients together with the pine bark extract. It is preferable to use a material. The sweetener of the present invention means one that exhibits sweetness, and is not limited to the purpose of use as a sweetener.

(C) Amino acid In the blood flow improving agent of the present invention, at least one selected from asparagine, aspartic acid, cysteine, glutamine, isoleucine, leucine, lysine, proline, and tryptophan as active ingredients together with the pine bark extract. It is preferable to use amino acids (including salts). Examples of the salt include sodium salts, hydrochlorides and the like.

(D) Polyphenol In the blood flow improving agent of the present invention, it is preferable to use at least one polyphenol selected from gallic acid and chlorogenic acid as an active ingredient together with the pine bark extract.

(E) Vitamins and minerals In the blood flow improving agent of the present invention, at least one vitamin selected from vitamin C, niacin, folic acid, inositol, zinc, iron, and magnesium as active ingredients together with the pine bark extract. -It is preferable to use minerals. In addition, zinc, iron, and magnesium as minerals of this invention include the form of the compound containing these metals.

The blood flow improving agent of the present invention is particularly limited as long as it contains a pine bark extract and a predetermined other component and can be distinguished from other products as a product in that it is used for improving blood flow. The scope of the present invention includes, for example, a product indicating that any of the main body, packaging, instruction manual, and promotional material of the product according to the present invention has a function of improving blood flow. For example, so-called health foods such as pharmaceuticals (including non-pharmaceutical products), foods for specified health use, foods with nutritional function, foods with functional claims, and other functional foods whose efficacy has been approved by a prescribed organization, feeds, etc. Can be mentioned. In so-called health foods, "improve circulation", "for those who are concerned about swelling", "for those who are concerned about skin color", "for those who are concerned about dark circles", "vascular function" "Increases the suppleness of blood vessels" and the like can be exemplified.

The form of the blood flow improving agent of the present invention includes, for example, tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, and pastes. Examples thereof include liquids, creams, capsules, gels, chewables, sticks and the like. Among these, the forms of tablets, capsules, powders, granules, and liquids are particularly preferable. Specifically, supplements, packaged beverages filled in PET bottles, cans, bottles, etc., instant powdered beverages for dissolving in water (hot water), milk, fruit juice, green juice, etc., and instant granule beverages. Can be exemplified. These are preferable in that they are easy to drink at the time of meals and can enhance the palatability.

The content of the pine bark extract and other components (active ingredients) in the blood flow improving agent of the present invention may be appropriately contained within the range in which the effect is exhibited.

In general, when the blood flow improving agent of the present invention is a drug or supplement (tablet, capsule), it is preferable that the active ingredient is contained in an amount of 0.0001 to 100% by mass in terms of dry mass. , 0.1 to 85% by mass is more preferable, and 0.5 to 70% by mass is further preferable.

When the blood flow improving agent of the present invention is a packaged beverage (liquid agent), it is preferable that the active ingredient is contained in an amount of 0.0001 to 15% by mass in terms of dry mass, and 0.001 to 12. It is more preferably contained in an amount of 5% by mass, and further preferably contained in an amount of 0.01 to 10% by mass.

When the blood flow improving agent of the present invention is an instant powdered beverage (powder) or an instant granule beverage (granule), the active ingredient is contained in an amount of 0.001 to 80% by mass in terms of dry mass. It is preferably contained in an amount of 0.005 to 70% by mass, more preferably 0.1 to 60% by mass.

In order to exert the effect of the present invention more effectively, it is preferable that the active ingredient is contained in an amount of 80% or more, and 90% or more, of the entire blood flow improving agent (excluding water) of the present invention in terms of dry mass. It is more preferable that the content is 95% or more, and 100% is particularly preferable. Further, when the blood flow improving agent of the present invention contains any of the components (a) to (e), it is preferable that the contained component is composed of only the active ingredient in the present invention. That is, when the blood flow improving agent of the present invention contains, for example, component (a) (plant material), it is preferable to configure the agent so as not to contain plant materials other than longevity grass, black ginger, coconut, ginger, and long pepper. ..

The intake amount of the blood flow improving agent of the present invention is not particularly limited, but from the viewpoint of exerting the effect of the present invention more remarkably, the intake amount of the active ingredient per day should be 0.1 mg / day or more. It is preferable to take it in an amount of 1 mg / day or more, more preferably it is taken in an amount of 10 mg / day or more, and it is particularly preferable to take it in an amount of 40 mg / day or more. preferable. The upper limit is not particularly limited, but is, for example, 4 g / day, preferably 2 g / day.

The blood flow improving agent of the present invention can be contained in one container or divided into a plurality of containers, for example, 2 to 3 so as to have the daily intake as the daily intake. ..

The compounding mass ratio of the pine bark extract and other components is preferably in the range of 0.5: 1 to 70: 1, preferably in the range of 0.75: 1 to 60: 1 in terms of dry mass. Is more preferable, and the range of 1: 1 to 60: 1 is more preferable, and the range of 1: 1 to 50: 1 is particularly preferable. When the blending ratio of the pine bark extract and other components is within the above range, the effect of the present invention can be more effectively exhibited.

The blood flow improving agent of the present invention can be produced by a known formulation method by adding an ingredient other than the active ingredient permitted for oral use, if necessary.

Further, examples of the blood flow improving agent of the present invention include foods for improving blood flow containing an active ingredient and foods for improving blood flow obtained by adding an active ingredient to foods. Examples thereof include foods in which the content of the active ingredient of the present invention is increased as compared with ordinary foods, and foods in which the active ingredient is added to foods that do not normally contain the active ingredient of the present invention. The active ingredient may be added separately, at the same time, or together with other ingredients other than the active ingredient.

Examples of the food for improving blood flow of the present invention include beverages such as carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, smoothies, and green juice; cold confectionery such as ice cream, ice sherbet, and shaved ice; buckwheat noodles, udon noodles, and harusame. Noodles such as Chinese noodles and instant noodles; Confectionery such as candy, candy, gum, chocolate, tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, baked confectionery, bread; Fisheries and livestock processing such as kamaboko, ham, sausage Foods; dairy products such as processed milk, fermented milk, yogurt; fats and oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing and their processed foods; seasonings such as sauces and soy sauce; curry, stew, parent and child Retort pouch foods such as bowls, porridge, miscellaneous dishes, Chinese bowls, katsudon, tempura bowls, beef bowls, hayashi rice, omelet rice, oden, marbodorf, dumplings, shumai, hamburgers, meat balls, various sauces, various soups, etc. it can.

The blood flow improving method of the present invention is characterized in that the blood flow improving agent of the present invention described above is ingested, but does not include medical practice. Examples of the method of the present invention include a method of improving blood flow by providing the food for improving blood flow of the present invention in a restaurant such as a restaurant.

Hereinafter, the present invention will be described based on examples.
[Example 1]
1. 1. Cell culture
(1) Fetal pulmonary artery vascular endothelial cells (PPAEC) were cultured in 10% FBS-RPMI 1640 in a 5% CO ₂ incubator at 37 ° C. using a 75 cm ² flask.
(2) Cells suspended by trypsin treatment were seeded from a 75 cm ² flask into each well of a 96-well plate at a cell density of 1.0 × 10 ⁴ cells / well.
(3) Pre-cultured at 37 ° C. in a 5% CO ₂ incubator for 48 hours.
(4) After removing the medium from each well, 100 μL of the test substance-containing medium prepared to a predetermined concentration with 4% FBS-αMEM was added, and the cells were cultured in a CO ₂ incubator for 16 hours.

For the combined sample of the pine bark extract and other components, 50 μL of each of the test substance-containing mediums having a double concentration was added to obtain the desired concentration. Regarding control, 4% FBS-αMEM containing 0.25% DMSO was used for the test substance dissolved in DMSO, and 4% FBS-αMEM was used for other test substances. Prepared.

As the pine bark extract, a hot water extract (dry powder) of the bark of French coastal pine was used. As the other components used together with the pine bark extract, the substances shown in Tables 1 to 5 were used.

2. 2. Evaluation of NO production
(1) After culturing for 16 hours, 50 μL of the culture supernatant was collected in a 1.5 mL sample tube, and a sample of N = 3 was mixed.
(2) Centrifugation was carried out at 4 ° C. and 2000 g for 3 minutes, and the supernatant was transferred to another 1.5 mL Eppen tube.
(3) The NO concentration (μM) in the sample of (2) was measured using Nitrate / Nitrite Assay Kit and Fluorometer (manufactured by Cayman). NO produced from vascular endothelial cells has the effect of relaxing the muscles around the blood vessels and expanding the blood vessels.
(4) “% of control” was calculated based on the calculated NO concentration.

% Of control
= NO concentration of sample (μM) / NO concentration of control (μM) × 100

The results are shown in Tables 1 to 5 and FIGS. 1 to 10. Each figure shows the results of "control (without addition)", "single addition of pine bark extract", "single addition of other components", and "addition of pine bark extract + other components" from the left. Further, the numerical values in the explanation at the bottom of the graph indicate the sample concentration, and for example, “pine_5” in the upper left graph of FIG. 1 indicates pine bark extract 5 (μg / mL). The concentration unit of the additive component is μg / mL in all graphs. The vertical axis shows "% of control".

For long-lived grass, dried and crushed leaves were used.
For black ginger, a 60% ethanol extract (dry powder) of the rhizome of black ginger was used.
As for coconut, commercially available coconut milk was dried and then oil-free was used.
For Zingiber officin, a hot water extract (dry powder) of the rhizome of Zingiber officin was used.
For long peppers, dried fruit powder was used.
For mugwort, finely ground powder of fresh leaves was used.

As shown in Tables 1 to 3 and FIGS. 1 to 10, the amount of NO produced was synergistically increased by combining the pine bark extract with the specific other components of the present invention. Therefore, according to the blood flow improving agent of the present invention, vasodilation is promoted, and blood flow can be effectively improved.

[Example 2] (Production of tablets)
A tablet (500 mg) composed of the following ingredients was produced.
Reduced maltose 5% by mass
Collagen peptide 15% by mass
Soy protein 15% by mass
Starch 15% by mass
Pine bark extract 8% by mass
Ginger extract 4% by mass
Long pepper extract 1% by mass
Vitamin C 1% by mass
Folic acid 1% by mass
Gallic acid 1% by mass
Cellulose 2% by mass
Silicon dioxide 2% by mass
Calcium stearate 1% by mass

[Example 3] (Production of capsule)
The following mixture was encapsulated in soft capsules to produce capsules.
Coconut milk powder 100mg
Isomaltooligosaccharide 50 mg
Maltose 50 mg
Pine bark extract 20 mg
Silicon dioxide 10 mg
Niacin 0.5 mg
Magnesium 1 mg

[Example 4] (Production of granules)
The following ingredients were mixed to produce granules by a conventional method.
Fructooligosaccharide 20g
Isomaltooligosaccharide 20g
Sucrose fatty acid ester 2g
Silicon dioxide 1g
Pine bark extract 0.4g
Chlorogenic acid 0.1g
Cysteine 0.001g
Zinc gluconate 0.001 g

[Example 5] (Production of instant powder)
The following components were mixed to produce an instant powder (10 g) by a conventional method.
Trehalose 0.1g
Reduced palatinose 0.1g
Sucrose fatty acid ester 2g
Longevity grass dried powder 2g
Black ginger 1g
Pine bark extract 0.4g
Gallic acid 0.02g
Glutamine 0.01g
Zinc gluconate 0.001 g
Iron chloride 0.001g
Calcium Stearate Remaining

[Example 6] (Production of liquid preparation)
A liquid preparation (500 mL) consisting of the following components was produced.
Black ginger extract 1.0% by mass
Maltose 0.3% by mass
Pine bark extract 0.08% by mass
Leucine 0.05% by mass
Isoleucine 0.02% by mass
Asparagine 0.01% by mass
Aspartic acid 0.01% by mass
Proline 0.01% by mass
Tryptophan 0.01% by mass
Vitamin C 0.001% by mass
Vitamin E 0.001% by mass
Remaining water

Since the blood flow improving agent of the present invention has an effect of improving blood flow and can be used as an oral agent, the industrial usefulness of the present invention is high.

Claims (1)

A blood flow improving agent comprising a pine bark extract and at least one selected from fructooligosaccharide, isomaltooligosaccharide, inositol, gallic acid, iron, magnesium, and long pepper.