JP2020002156A - Blood flow improving composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a blood flow improving composition having a high blood flow improving effect. SOLUTION: The composition is characterized by containing citrulline and at least one amino acid selected from tyrosine, threonine, tryptophan, and proline as an active ingredient. [Selection diagram] Fig. 1

Description

  The present invention relates to a composition having a blood flow improving effect, and more particularly to a composition containing citrulline and certain other components as active ingredients.

  In modern society, various factors such as lack of exercise and autonomic imbalance due to stress often cause problems with blood circulation (blood flow). This disorder of blood flow (decrease in blood flow) causes various symptoms such as headache, stiff shoulders, dull skin, coldness, swelling and the like. There is a need for ways to improve the flow.

  Examples of such a composition for improving blood flow include a hyssop 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 ( Patent Document 3) has been proposed.

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

JP 2006-8575 A JP 2004-262878 A JP 2005-68069 A JP 2012-051833 A

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

  The present inventors have conducted extensive research and research on the blood flow improving ability of citrulline, and found that a high blood flow improving effect can be obtained by combining citrulline with certain other components, and completed the present invention. Reached. That is, it has been found that the blood flow improving ability can be synergistically improved by combining citrulline with a specific component having little or low blood flow improving ability.

That is, the present invention relates to a composition comprising citrulline and at least one component selected from the group consisting of the following (a) to (e) as active ingredients.
(A) at least one plant material selected from terminaria, rice, maqui berry, black ginger, ginger, and pepper; (b) at least one selected from maltose, trehalose, reduced palatinose, reduced maltose, calcium stearate, and shellac Functional additives (c) at least one amino acid selected from leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine (d) gallic acid (e) vitamin A, vitamin B1, vitamin B2, At least one vitamin or mineral selected from vitamin C, sodium pantothenate, niacin, folic acid, biotin, vitamin K, inositol, calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium

.
The composition of the present invention may be obtained by adding an active ingredient comprising citrulline and at least one component selected from the group consisting of (a) to (e).

In the composition of the present invention, the compounding mass ratio of citrulline and other active ingredients is preferably in the range of 0.5: 1 to 70: 1.
Further, the composition of the present invention is preferably a tablet, capsule, powder, granule, or liquid.

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

  ADVANTAGE OF THE INVENTION According to the composition of this invention, a blood flow can be increased and a high blood flow improving effect can be obtained.

It is a figure which shows the result of NO production amount when the composition (citrulline + plant material) of this invention is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The upper left graph shows the use of terminaria as a plant material, the upper right graph uses rice (rice bran) as a plant material, and the lower left graph uses maqui berry as a plant material. The graph on the lower right shows the use of black ginger as a plant material. It is a figure which shows the result of NO production amount when the composition (citrulline + plant material) of this invention is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The graph on the left shows the use of ginger as a plant material, and the graph on the right shows the use of pepper (bioperine) as a plant material. It is a figure which shows the result of NO production amount when the composition of the present invention (citrulline + functional additive) is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The upper left graph shows the use of maltose as the functional additive, the upper right graph shows the use of trehalose as the functional additive, and the lower left graph shows the use of reduced palatinose as the functional additive. The graph at the lower right shows the use of reduced maltose as a functional additive. It is a figure which shows the result of NO production amount when the composition of the present invention (citrulline + functional additive) is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The graph on the left shows the use of calcium stearate as the functional additive, and the graph on the right shows the use of shellac as the functional additive. It is a figure which shows the result of NO production amount when the composition of the present invention (citrulline + amino acid) is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The upper left graph is a graph using leucine as an amino acid, the upper right graph is a graph using methionine as an amino acid, the lower left graph is a graph using phenylalanine as an amino acid, and the lower right graph is And proline as an amino acid. It is a figure which shows the result of NO production amount when the composition of the present invention (citrulline + amino acid) is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The upper left graph is a graph using serine as an amino acid, the upper right graph is a graph using threonine as an amino acid, the lower left graph is a graph using tryptophan as an amino acid, and the lower right graph is And tyrosine as an amino acid. It is a figure which shows the result of the amount of NO production when the composition (citrulline + amino acid) of this invention is applied to a porcine pulmonary artery vascular endothelial cell (PPAEC), and uses valine as an amino acid. It is a figure which shows the result of NO production amount when the composition (citrulline + polyphenol) of this invention is applied to a porcine pulmonary artery vascular endothelial cell (PPAEC), and uses gallic acid as a polyphenol. It is a figure which shows the result of NO production amount when the composition (citrulline + vitamin / minerals) of the present invention is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The graph on the upper left shows the case using vitamin A as the vitamins, the graph on the upper right shows the case using vitamin B1 as the vitamins, and the graph on the lower left shows the case using vitamin B2 as the vitamins. The graph on the lower right shows the case using vitamin C as vitamins. It is a figure which shows the result of NO production amount when the composition (citrulline + vitamin / minerals) of the present invention is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The graph on the upper left is the one using sodium pantothenate as the vitamins, the graph on the upper right is the one using niacin as the vitamins, and the lower left graph is the one using folic acid as the vitamins, The graph on the lower right shows the use of biotin as vitamins. It is a figure which shows the result of NO production amount when the composition (citrulline + vitamin / minerals) of the present invention is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The graph on the left shows the case using vitamin K as the vitamins, and the graph on the right shows the case using inositol as the vitamins. It is a figure which shows the result of NO production amount when the composition (citrulline + vitamin / minerals) of the present invention is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The graph on the upper left is a graph using calcium as a mineral, the graph on the upper right is a graph using zinc as a mineral, and the graph on the lower left is a graph using iron as a mineral. Is a graph using copper as a mineral. It is a figure which shows the result of NO production amount when the composition (citrulline + vitamin / minerals) of the present invention is applied to porcine pulmonary artery vascular endothelial cells (PPAEC). The upper left graph is a graph using selenium as a mineral, the upper right graph is a graph using molybdenum as a mineral, and the lower left graph is a graph using magnesium as a mineral. Is a graph using chromium as a mineral.

  The composition of the present invention is characterized by containing citrulline and at least one component selected from the group consisting of the following (a) to (e) (hereinafter sometimes referred to as other components) as active ingredients. I do. The following components (a) to (e) used together with citrulline may be used alone (for example, component (a)), or may be used in combination of two or more. When two or more other components are used in combination, it is preferable to combine citrulline with other components having a high synergistic effect.

  The composition (blood flow improving composition) of the present invention can more effectively relax muscles around blood vessels, dilate blood vessels, and increase blood flow by a synergistic effect of the combination of the active ingredients. It can effectively prevent or ameliorate symptoms such as headache, stiff shoulders, dull skin, coldness, and erectile dysfunction.

[Citrulline]
Citrulline as an active ingredient of the blood flow improving composition of the present invention may be L-citrulline or D-citrulline, but is preferably L-citrulline. Citrulline may be produced by any method, including those obtained by chemical synthesis and those obtained by fermentation. Citrulline may be in the form of a salt, and the salt is not particularly limited as long as it is a pharmaceutically acceptable salt. For example, inorganic acid salts, organic acid salts, metal salts, and ammonium salts Salts may be mentioned. Citrulline is commercially available as pharmaceuticals, reagents, and the like, and these commercially available products can be used.

[Other components]
(A) Plant material In the blood flow improving composition of the present invention, it is preferable to use at least one plant material selected from terminaria, rice, maqui berry, black ginger, ginger, and pepper as an active ingredient together with citrulline. .

  These plant materials may be any part of a plant, such as leaves, stems, roots, flowers, fruits, stems, branches, etc., as well as plant materials themselves (including dried products), crushed products, and squeezed juices , Extract, etc., can be used. Examples of the pulverized product include a powder and a granule. The squeezed juice and the extract may be liquid, but may be used as a paste or a dry powder. The extract can be obtained by extraction using an appropriate solvent. As the solvent, for example, water (hot water, hot water), ethanol, or hydrated ethanol can be used. As these plant materials, commercially available ones can be used.

  Examples of the terminaria include Terminalia bellirica (belerica), Terminalia catappa, Terminalia tomentosa, Terminalia citrina, Terminalia phellocarpa, Terminalia copelandii, Terminalia brassi, Terminalia ivorensis, Terminalia superba, Terminalia arjuna, Terminalia chebula and the like. Among them, Terminalia bellirica (belerica) and Terminalia chebula are preferred. Fruits are preferred as the site used as the plant material of the present invention.

  Rice is a plant belonging to the genus Poaceae. As the site used as the plant material of the present invention, the outer skin or embryo of brown rice is preferable, and specifically, it is preferable to use rice bran obtained as a by-product when milling brown rice. There are no particular restrictions on the type of rice, and examples include Japonica and Indica species.

  Machiberry is a plant belonging to the family Poaceae in Patagonia, Chile, and its scientific name is Aristotellia chilensis. Fruits are preferred as the site used as the plant material of the present invention.

  Black ginger is scientifically named Kaempferia Parviflora and is a plant belonging to the genus Ginger in the genus Ginsidae native to Southeast Asia. As a part used as a plant material of the present invention, a rhizome is preferable.

  Ginger is a plant belonging to the genus Ginger in the ginger family and includes, for example, ginger ginseng, yellow ginger, golden ginger, and yanaka ginger. Red ginger (Zingiber officinale var. Rubra) cultivated in Indonesia and India can also be preferably used. As a part used as a plant material of the present invention, a rhizome is preferable.

  Pepper is a plant belonging to the family Pepper (Piper nigrum), and the site used as the plant material of the present invention is preferably a fruit. From the timing of harvesting and the like, there are types such as black pepper, white pepper and red pepper, and any type may be used, but black pepper is preferred. Black pepper is obtained by drying immature fruits obtained from a pepper tree and contains a pungent component piperine. As the pepper of the present invention, those containing this piperine are preferred.

(B) Functional additive In the blood flow improving composition of the present invention, at least one functional additive selected from maltose, trehalose, reduced palatinose, reduced maltose, calcium stearate, and shellac as active ingredients together with citrulline. It is preferable to use an agent.

(C) Amino acids In the blood flow improving composition of the present invention, together with citrulline, at least one amino acid (salt) selected from leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine as an active ingredient Is preferable. Examples of the salt include a sodium salt, a hydrochloride, and the like.

(D) Gallic acid In the blood flow improving composition of the present invention, it is preferable to use gallic acid as an active ingredient together with citrulline.

(E) Vitamins and Minerals In the blood flow improving composition of the present invention, together with citrulline, as active ingredients, vitamin A, vitamin B1, vitamin B2, vitamin C, sodium pantothenate, niacin, folic acid, biotin, vitamin K, It is preferable to use at least one vitamin or mineral selected from inositol, calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium. In addition, calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium as minerals of the present invention include forms of compounds containing these metals.

  The blood flow improving composition of the present invention can be used as a blood flow improving agent having a blood flow improving effect. Such a blood flow improving agent contains citrulline and certain other components, and is used for improving blood flow. Is not particularly limited as long as it can be distinguished from other products as a product. For example, any of the main body, the packaging, the instruction manual, and the advertisement of the product according to the present invention indicating that it has a blood flow improving function is included in the scope of the present invention. For example, so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods for which the indication of efficacy has been approved by a specified organization such as foods for specified health use, nutritional functional foods, and functionally labeled foods, feeds, etc. Can be mentioned. In so-called health foods, "Improve circulation", "Improve chilling", "For those who are worried about swelling", "For those who are worried about skin color", "Worry for dark eyes" , "Enhancing vascular function", "enhancing vascular suppleness", "in support of male function", "in the vitality of men" and the like can be exemplified. The blood flow improving agent of the present invention can be taken regardless of gender and age if the above-mentioned effect is a concern for a person, but the effect of the blood flow improving agent of the present invention can be more effectively enjoyed. Because it is possible, it is desirable that healthy people except the sick take it, and it is desirable that elderly people who have the above-mentioned troubles take it. In addition, it is desirable to take the drug at night because the effect of improving coldness and the improvement of male function can be obtained.

  Examples of the form of the blood flow improving composition of the present invention include, for example, tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, pills, Examples include pastes, creams, caplets, gels, chewables, and sticks. Among these, the forms of tablets, capsules, powders, granules and liquids are particularly preferred. Specifically, packaged beverages filled in supplements, plastic bottles, cans, bottles, and the like; instant powdered beverages and instant granulated beverages for dissolving and drinking in water (hot water), milk, fruit juice, green juice, etc. Can be exemplified. These are preferred in that they are easily drinkable at the time of a meal or the like and can enhance palatability.

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

  Generally, when the blood flow improving composition of the present invention is a drug or supplement (tablet, capsule), the active ingredient may be contained in an amount of 0.0001 to 100% by mass in terms of dry mass. Preferably, it is contained in an amount of 0.1 to 85% by mass, more preferably 0.5 to 70% by mass.

  When the blood flow improving composition of the present invention is a packaged beverage (solution), the active ingredient is preferably contained in an amount of 0.0001 to 15% by mass in terms of dry mass, and 0.001 to 12% by mass. The content is more preferably 0.5% by mass, and even more preferably 0.01 to 10% by mass.

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

  In order to more effectively exert the effects of the present invention, it is preferable that the active ingredient is contained in an amount of 80% or more of the whole blood flow improving composition (excluding water) of the present invention in terms of dry mass, and 90% or more. It is more preferably contained, more preferably 95% or more, and particularly preferably 100%. Further, when the blood flow improving composition of the present invention contains any of the components (a) to (e), it is preferable that the contained component is constituted only by the active ingredient of the present invention. That is, when the blood flow improving composition of the present invention contains, for example, the component (a) (plant material), it should be configured so as not to contain plant materials other than terminaria, rice, maqui berry, black ginger, ginger, and pepper. Is preferred.

  The amount of the blood flow improving composition of the present invention is not particularly limited, but from the viewpoint of more remarkably exhibiting the effects of the present invention, the amount of the active ingredient per day should be 200 mg / day or more. It is preferably taken, more preferably at 400 mg / day or more, and even more preferably at 600 mg / day or more. The upper limit is not particularly limited, but is, for example, 10 g / day, preferably 8 g / day.

  The blood flow improving composition of the present invention may be housed in one container or, for example, divided into a plurality of two or three containers so that the daily intake is the above intake, and accommodated as one day. it can.

  The compounding mass ratio of citrulline and other components is preferably in the range of 0.5: 1 to 70: 1, more preferably 0.75: 1 to 60: 1 in terms of dry mass. , 1: 1 to 60: 1, more preferably 1: 1 to 50: 1. When the mixing ratio of citrulline and other components is within the above range, the effects of the present invention can be more effectively exerted.

  The blood flow improving composition of the present invention can be produced by a known formulation method, if necessary, by adding components other than the orally acceptable active ingredient.

  Examples of the blood flow improving composition of the present invention include blood flow improving foods containing an active ingredient, and blood flow improving foods obtained by adding an active ingredient to foods. Foods in which the content of the active ingredient of the present invention is increased as compared with the foods of the above, and foods in which the active ingredient is added to foods which do not usually contain the active ingredient of the present invention. The active ingredients may be added separately or simultaneously, or may be added together with other ingredients other than the active ingredients.

  Examples of the blood flow improving food of the present invention include drinks such as carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, smoothies, green juices, etc .; ice creams, ice sorbets, shaved ice, etc .; Noodles such as noodles and instant noodles; sweets such as candy, candy, gum, chocolate, tablets, snacks, biscuits, jellies, jams, creams, baked goods, breads, etc .; Dairy products such as processed milk, fermented milk, yogurt; oils and fats such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing and processed foods; seasonings such as sauces, soy sauce; , Porridge, porridge, Chinese rice bowl, katsudon, tendon, gyudon, hayashi rice, omelet, oden, marbodeau , Mention may be made of dumplings, Shumai, hamburger, meatballs, various sources, retort pouch foods such as various soups and the like.

  The blood flow improving method of the present invention is characterized by ingesting the blood flow improving composition of the present invention described above, but does not include medical practice. The blood flow improving composition of the present invention can be taken regardless of gender and age if the above-mentioned effects are of concern to a person, but more effectively enjoy the effects of the blood flow improving composition of the present invention. Therefore, it is desirable that healthy people excluding the sick person take the ingestion, and it is even more desirable that the elderly people who have the above-mentioned troubles take the ingestion. In addition, it is desirable to take the drug at night because the effect of improving coldness and the function of males can be obtained. Examples of the method of the present invention include a method of improving blood flow by providing the blood flow improving food of the present invention in a restaurant such as a restaurant.

Hereinafter, the present invention will be described based on examples.
[Example 1]
1. Cell culture
(1) Porcine pulmonary artery vascular endothelial cells (PPAEC) were cultured with 10% FBS-RPMI 1640 using a 75 cm ² flask in a 5% CO ₂ incubator at 37 ° C.
(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) The cells were pre-cultured in a 5% CO ₂ incubator at 37 ° C. for 48 hours.
(4) After removing the medium from each well, 100 μL of a test substance-containing medium adjusted to a predetermined concentration with 4% FBS-αMEM was added thereto, and the cells were cultured in a CO ₂ incubator for 24 hours.

  In addition, about the combined sample of citrulline and other components, the target concentration was obtained by adding 50 μL of the test substance-containing medium at a double concentration, respectively. The control was prepared by dissolving the test substance in DMSO using 4% FBS-αMEM containing 0.25% DMSO, and using 4% FBS-αMEM for the other test substances. Prepared.

  For citrulline, commercially available citrulline was used. The substances shown in Tables 1 to 5 were used as other components used together with citrulline.

2. Evaluation of NO production
(1) After culturing for 24 hours, 50 μL of the culture supernatant was collected in a 1.5 mL sample tube, and N = 3 samples were mixed.
(2) The mixture was centrifuged at 2000 g for 3 minutes at 4 ° C., and the supernatant was transferred to another 1.5 mL Eppendorf tube.
(3) The NO concentration (μM) in the sample of (2) was measured using the Nitrate / Nitrite Assay Kit, Fluorometric (manufactured by Cayman). NO produced from vascular endothelial cells has the effect of relaxing muscles around blood vessels and expanding 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) x 100

  The results are shown in Tables 1 to 5 and FIGS. Each figure shows the results of “control (no addition)”, “single addition of citrulline”, “single addition of other components”, and “addition of citrulline + other components” from the left. The numerical values in the description at the bottom of the graph indicate the sample concentration. For example, “citrulline — 31.2” in the upper left graph of FIG. 1 indicates citrulline 31.2 (μg / mL). The concentration unit of the added component is μg / mL in all the graphs. The vertical axis indicates “% of control”.

For Terminaria, a hot water extract (dry powder) of the fruit was used.
Commercial rice bran was used.
For long-lived grasses, dried and crushed leaves were used.
For maki berry, a dried powder of a commercially available fruit was used.
For black ginger, a 60% ethanol extract (dry powder) of the rhizome of black ginger was used.
For ginger, a hot water extract (dry powder) of the ginger rhizome was used.
For pepper, a 100% ethanol extract of black pepper was used.
For mugwort, finely ground powder of fresh leaves was used.
As for caffeine, commercially available caffeine was used.

  As shown in Tables 1 to 5 and FIGS. 1 to 13, the production of NO increased synergistically by combining citrulline with the specific other components of the present invention. Therefore, according to the blood flow improving composition of the present invention, the expansion of blood vessels is promoted, and the blood flow can be effectively improved.

[Example 2] (Production of tablets)

Six tablets (7200 mg) comprising the following components were produced.
Reduced maltose 5% by mass
Citrulline 80% by mass
Ginger extract 4% by mass
2% by mass of pepper extract
Vitamin C 1% by mass
Folic acid 1% by mass
1% by weight of gallic acid
Cellulose 2% by mass
2% by mass of silicon dioxide
1% by mass of calcium stearate
Shellac 1% by mass

  The tablets are taken with water, divided into two or three times a day.

[Example 3] (Production of capsule)
The following mixture was encapsulated in soft capsules to produce capsules.

Citrulline 200mg
Black ginger powder 100mg
Maltose 50mg
Silicon dioxide 10mg
Niacin 5mg
Vitamin B1 5mg
Vitamin B2 5mg
Leucine 2.5mg
Tyrosine 2.5mg
Valine 2.5mg
1mg iron chloride

  The above capsules are taken with 8 tablets of water 2 to 4 times a day with water.

Example 4 (Production of granules)
The following components were mixed to produce a granule (5000 mg) by a conventional method.

Citrulline 3000mg
Terminaria Bellirica Powder 400mg
Reduced palatinose 500mg
200mg silicon dioxide
Sucrose fatty acid ester 50mg
Inositol 25mg
Biotin 10mg
10mg zinc gluconate
Magnesium chloride 5mg
5 mg threonine
Tryptophan 2.5mg
Starch rest

[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
2g calcium stearate
Black ginger extract (dry powder) 1g
Citrulline 1g
Gallic acid 0.02g
Glutamine 0.01g
0.001 g of zinc gluconate
Iron chloride 0.001g
Water-soluble cellulose balance

[Example 6] (Production of liquid agent)
A liquid (500 mL) comprising the following components was produced.
Makiberry extract 3000mg
Trehalose 250mg
Citrulline 300mg
Vitamin K 150mg
50mg calcium chloride
Valine 25mg
Leucine 25mg
Isoleucine 25mg
Phenylalanine 10mg
Proline 10mg
Vitamin C 500mg
Vitamin A 120mg
Vitamin B1 60mg
Vitamin B2 60mg
Zinc gluconate 50mg
Water remaining

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

Claims (1)

  A composition comprising citrulline and at least one amino acid selected from tyrosine, threonine, tryptophan and proline as active ingredients.

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