Bloodstream ameliorating composition

Abstract

To provide a bloodstream ameliorating composition having a high bloodstream ameliorating effect.SOLUTION: A bloodstream ameliorating component characteristically contains citrulline and specific components of vegetable materials such as Terminalia, rice, Maqui berry and black ginger, ginger and pepper as active ingredients.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a composition having a blood flow improving effect, and more particularly to a composition containing citrulline and specific other components as active ingredients.

Background Art

[0002] In modern society, due to various factors such as lack of exercise and autonomic nerve disorders caused by stress, blood circulation (blood flow) disorders often become problems. This blood flow disorder (decrease in blood flow volume) causes various symptoms such as headache, stiff shoulders, dullness of the skin, cold sensitivity, and swelling. Therefore, from the viewpoints of health and beauty, measures to increase blood flow volume and improve blood flow are required.

[0003] As such compositions for improving blood flow, for example, a hyssop extract (see Patent Document 1), a composition containing a blackcurrant concentrate and an amino acid or an organic acid (see Patent Document 2), a chamomile extract (see Patent Document 3), etc. have been proposed.

[0004] On the other hand, the applicant of the present application has proposed a composition for improving blood flow containing a pine bark extract and a black pepper extract (see Patent Document 4).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0006] An object of the present invention is to provide a composition having a high blood flow improving effect.

Means for Solving the Problems

[0007] The present inventors earnestly investigated and studied the blood flow improving ability of citrulline, and as a result, found that a high blood flow improving effect can be obtained by combining citrulline with a specific other component, and thus completed the present invention. That is, it was found that by combining citrulline with a specific other component having little or small blood flow improving ability, the blood flow improving ability can be synergistically improved.

[0008] That is, the present invention relates to a composition characterized by containing 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 Terminalia, rice, maqui berry, black ginger, ginger, and pepper (b) At least one functional additive selected from maltose, trehalose, reduced palatinose, reduced maltose, calcium stearate, and shellac (c) At least one amino acid selected from leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine (d) Gallic acid (e) At least one vitamin and minerals selected from vitamin A, vitamin B1, vitamin B2, vitamin C, sodium pantothenate, niacin, folic acid, biotin, vitamin K, inositol, calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium

[0009] 。 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).

[0010] In the composition of the present invention, the blending mass ratio of citrulline and other active ingredients is preferably in the range of 0.5:1 to 70:1. Moreover, the composition of the present invention is preferably a tablet, capsule, powder, granule, or liquid.

[0011] The present invention also relates to a method for improving blood flow (excluding medical acts) characterized by ingesting the composition of the present invention.

Effects of the Invention

[0012] According to the composition of the present invention, it is possible to increase blood flow volume and obtain a high blood flow improvement effect.

Brief Description of the Drawings

[0013]

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Mode for Carrying Out the Invention

[0014] 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. The components of the following (a) to (e) used together with citrulline may be used alone (for example, component (a)) or in combination of two or more. When using two or more other components in combination, it is preferable to combine other components having a high synergistic effect with citrulline.

[0015] Due to the synergistic effect of such a combination of active ingredients, the composition of the present invention (blood flow improving composition) can more effectively relax the muscles around blood vessels, dilate blood vessels, and increase blood flow volume, and can effectively prevent or improve symptoms such as headache, stiff shoulders, dullness of the skin, coldness in the extremities, and erectile dysfunction.

[0016] [Citrulline] As citrulline, which is an active ingredient of the blood flow improving composition of the present invention, it may be L-citrulline or D-citrulline, but L-citrulline is preferable. The production method of citrulline is not limited, such as those obtained by chemical synthesis or fermentation. Also, 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, and examples include inorganic acid salts, organic acid salts, metal salts, and ammonium salts. Citrulline is commercially available as pharmaceuticals, reagents, etc., and these commercial products can be used.

[0017] [Other components] (a) Plant materials In the blood flow improving composition of the present invention, it is preferable to use at least one plant material selected from Terminalia, rice, maca berry, black ginger, ginger, and pepper as an active ingredient together with citrulline.

[0018] These plant materials can 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), processed plant materials such as their pulverized products, squeezed juices, extracts, etc. can be used. Examples of the pulverized products include powders, granules, etc. The squeezed juice or extract may be in a liquid state, but can also be used in the form of a paste or dried powder. The extract can be obtained by extraction using an appropriate solvent. As the solvent, for example, water (warm water, hot water), ethanol, or hydrous ethanol can be used. These plant materials can be commercially available ones.

[0019] Examples of Terminalia include Terminalia bellirica (belerica), Terminalia catappa, Terminalia tomentosa, Terminalia citrina, Terminalia phellocarpa, Terminalia copelandii, Terminalia brassi, Terminalia ivorensis, Terminalia superba, Terminalia arjuna, Terminalia chebula, etc. Among these, Terminalia bellirica (belerica) and Terminalia chebula are preferred. As the part used as the plant material of the present invention, the fruit is preferred.

[0020] Rice is a plant of the genus Oryza in the family Poaceae. As the part used as the plant material of the present invention, the outer skin and embryo of brown rice are preferred. Specifically, it is preferable to use rice bran obtained as a by-product when polishing brown rice. There is no particular limitation on the type of rice, and examples include Japonica rice, Indica rice, etc.

[0021] Maqui berry is a plant of the family Brunelliaceae native to Patagonia, Chile, and its scientific name is Aristotellia chilensis. As the part used as the plant material of the present invention, the fruit is preferred.

[0022] Black ginger, scientifically known as Kaempferia Parviflora, is a plant of the genus Boesenbergia in the Zingiberaceae family that grows wild in Southeast Asia. As the part to be used as the plant material of the present invention, the rhizome is preferred.

[0023] Ginger is a plant of the genus Zingiber in the Zingiberaceae family, and examples include Sanzhou ginger, yellow ginger, Kintoki ginger, and Tanaka ginger. Also, red ginger (Zingiber officinale var. Rubra) cultivated in Indonesia and India can also be preferably used. As the part to be used as the plant material of the present invention, the rhizome is preferred.

[0024] Black pepper is a plant of the Piperaceae family (Piper nigrum), and as the part to be used as the plant material of the present invention, the fruit is preferred. Due to factors such as the timing of harvesting, 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 the unripe fruits taken from the pepper plant and contains the pungent component piperine. As the black pepper of the present invention, those containing this piperine are preferred.

[0025] (b) Functional additive In the blood flow improvement composition of the present invention, together with citrulline, as an active ingredient, it is preferable to use at least one functional additive selected from maltose, trehalose, reduced palatinose, reduced maltose, calcium stearate, and shellac.

[0026] (c) Amino acid In the blood flow improvement composition of the present invention, together with citrulline, as an active ingredient, it is preferable to use at least one amino acid (including salts) selected from leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. Examples of the salts include sodium salt, hydrochloride, etc.

[0027] (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.

[0028] (e) Vitamins and minerals In the blood flow improving composition of the present invention, it is preferable to use at least one kind of vitamins and minerals selected from vitamin A, vitamin B1, vitamin B2, vitamin C, sodium pantothenate, niacin, folic acid, biotin, vitamin K, inositol, calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium as an active ingredient together with citrulline. Note that calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium as minerals of the present invention include forms of compounds containing these metals.

[0029] The blood flow improving composition of the present invention can be used as a blood flow improving agent having a blood flow improving action. Such a blood flow improving agent contains citrulline and predetermined other components, and is not particularly limited as long as it can be distinguished from other products as a product in terms of being used for blood flow improvement. For example, those having a function of improving blood flow indicated in any of the main body, packaging, instruction manual, and promotional materials of the product according to the present invention are included in the scope of the present invention. Examples include pharmaceuticals (including quasi-drugs), so-called health foods such as functional foods whose efficacy has been approved by a predetermined institution such as specific health foods, nutrient-functional foods, and foods with functional claims, and feeds. In so-called health foods, examples include those labeled with "improving circulation", "improving cold sensitivity", "for those concerned about swelling", "for those concerned about skin color", "for those concerned about dark circles under the eyes", "enhancing blood vessel function", "enhancing blood vessel flexibility", "supporting male function", "enhancing male vitality", etc. The blood flow improving agent of the present invention can be ingested regardless of gender and age as long as the person is concerned about the above effects. However, since the effects of the blood flow improving agent of the present invention can be more effectively enjoyed, it is desirable for healthy people excluding those with diseases to ingest it, and it is also desirable for elderly people having the above concerns to ingest it. Also, since an effect of improving cold sensitivity and an effect of improving male function can be obtained, it is desirable to ingest it at night.

[0030] 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, pastes, creams, caplets, gels, chewables, sticks, etc. Among these, the forms of tablets, capsules, powders, granules, and liquids are particularly preferred. Specifically, supplements, container-packed beverages filled in PET bottles, cans, bottles, etc., instant powder beverages and instant granule beverages for dissolving and drinking in water (hot water), milk, fruit juice, green juice, etc. can be exemplified. These are preferable in that they can be easily drunk during meals and can enhance palatability.

[0031] The content of citrulline and other components (active ingredients) in the blood flow improving composition of the present invention may be appropriately contained within the range in which the effect is exhibited.

[0032] Generally, when the blood flow improving composition of the present invention is a pharmaceutical 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, more preferably 0.1 to 85% by mass, and even more preferably 0.5 to 70% by mass.

[0033] When the blood flow improving composition of the present invention is a container-packed beverage (liquid), it is preferable that the active ingredient is contained in an amount of 0.0001 to 15% by mass in terms of dry mass, more preferably 0.001 to 12.5% by mass, and even more preferably 0.01 to 10% by mass.

[0034] Further, when the blood flow improving composition of the present invention is an instant powder beverage (powder) or an instant granule beverage (granule), it is preferable that the active ingredient is contained in an amount of 0.001 to 80% by mass in terms of dry mass, more preferably 0.005 to 70% by mass, and even more preferably 0.1 to 60% by mass.

[0035] In order to more effectively exhibit the effects of the present invention, it is preferable that the active ingredient is contained in an amount of 80% or more, more preferably 90% or more, still more preferably 95% or more, and particularly preferably 100% of the entire blood flow improving composition of the present invention (excluding moisture) in terms of dry mass. Further, when the blood flow improving composition of the present invention contains any one of components (a) to (e), the contained component is preferably composed of only the active ingredient in the present invention. That is, when the blood flow improving composition of the present invention contains, for example, component (a) (plant material), it is preferably configured not to contain plant materials other than Terminalia, rice, maqui berry, black ginger, ginger, and pepper.

[0036] The intake amount of the blood flow improving composition of the present invention is not particularly limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, it is preferable to intake the active ingredient at 200 mg / day or more, more preferably 400 mg / day or more, and still more preferably 600 mg / day or more per day. The upper limit is not particularly limited, but for example, it is 10 g / day, preferably 8 g / day.

[0037] The blood flow improving composition of the present invention can be contained in one container or, for example, divided into a plurality of 2 to 3 containers so that the intake amount per day is the above intake amount, and contained as one day's portion.

[0038] The blending mass ratio of citrulline and other components is preferably in the range of 0.5:1 to 70:1, more preferably in the range of 0.75:1 to 60:1, still more preferably in the range of 1:1 to 60:1, and particularly preferably in the range of 1:1 to 50:1 in terms of dry mass. By the blending ratio of citrulline and other components being in the above range, the effects of the present invention can be more effectively exhibited.

[0039] The blood flow improving composition of the present invention can be produced by a known formulation method by adding components other than the active ingredient acceptable for oral use, if necessary.

[0040] In addition, examples of the blood flow improvement composition of the present invention include, in addition to blood flow improvement foods containing an active ingredient, blood flow improvement foods obtained by adding an active ingredient to foods. For example, foods with an increased content of the active ingredient of the present invention compared to ordinary foods, or foods to which an active ingredient is added to foods that do not normally contain the active ingredient of the present invention can be mentioned. The addition of the active ingredient may be carried out by adding each component separately, simultaneously, or together with other components other than the active ingredient.

[0041] Examples of the blood flow improvement foods of the present invention include, for example, beverages such as carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, smoothies, and green juices; frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as buckwheat noodles, udon noodles, glass noodles, Chinese noodles, and instant noodles; confectioneries such as candies, candies, gums, chocolates, tablet confections, snack foods, biscuits, jellies, jams, creams, baked confections, and breads; fishery and livestock processed foods such as kamaboko, ham, and sausages; dairy products such as processed milk, fermented milk, and yogurt; oils and fats such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressing, and processed foods thereof; seasonings such as sauces and soy sauces; retort pouch foods such as curries, stews, oyakodon, rice porridge, mixed rice, Chinese rice bowls, cutlet bowls, tempura bowls, beef bowls, hayashi rice, omurice, oden, mapo tofu, dumplings, shumai, hamburgers, meatballs, various sauces, and various soups, etc.

[0042] As a method for improving blood flow according to the present invention, it is characterized by having a subject ingest the blood flow improving composition of the present invention described above, but does not include medical acts. The blood flow improving composition of the present invention can be ingested by anyone who is concerned about the above effects, regardless of gender or age. However, since the effects of the blood flow improving composition of the present invention can be more effectively enjoyed, it is desirable to have healthy people other than those with diseases ingest it, and it is even more desirable to have elderly people with the above concerns ingest it. Further, since an effect of improving cold sensitivity and an effect of improving male functions can be obtained, it is desirable to ingest it at night. As a method of the present invention, for example, a method of improving blood flow by providing the blood flow improving food of the present invention in a restaurant such as a restaurant can be mentioned.

Examples

[0043] Hereinafter, the present invention will be described based on examples. [Example 1] 1. Cell culture (1) In an incubator at 37 ° C and 5% CO 2 , porcine pulmonary artery endothelial cells (PPAEC) were cultured with 10% FBS-RPMI 1640 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 for 48 hours in an incubator at 37 ° C and 5% CO 2 . (4) After removing the medium from each well, 100 μL of a test substance-containing medium prepared to a predetermined concentration with 4% FBS-αMEM was added, and cultured in a CO 2 incubator for 24 hours.

[0044] For the combined samples of citrulline and other components, the target concentration was achieved by adding 50 μL each of the test substance-containing medium at twice the concentration. For the control, when the test substance was dissolved in DMSO, it was prepared using 4% FBS-αMEM containing 0.25% DMSO, and for other test substances, it was prepared using 4% FBS-αMEM.

[0045] For citrulline, commercially available citrulline was used. As other components used together with citrulline, the substances shown in Tables 1 to 5 were used.

[0046] 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 samples with N = 3 were mixed. (2) Centrifuged at 2000 g for 3 minutes at 4°C, and the supernatant was transferred to another 1.5 mL Eppendorf tube. (3) Using the Nitrate / Nitrite Assay Kit, Fluorometric (manufactured by Cayman), the NO concentration (μM) in the sample of (2) was measured. Note that NO produced from vascular endothelial cells has the effect of relaxing the muscles around the blood vessels and dilating the blood vessels. (4) Based on the calculated NO concentration, "% of control" was calculated.

[0047] % of control = NO concentration of the sample (μM) / NO concentration of the control (μM) × 100

[0048] The results are shown in Tables 1 to 5 and Figures 1 to 13. Each figure represents, from left to right, the results of "control (no addition)", "addition of citrulline alone", "addition of other components alone", and "addition of citrulline + other components". Also, the numerical values in the descriptions at the bottom of the graphs indicate the sample concentrations. For example, "citrulline_31.2" in the upper left graph of Figure 1 indicates citrulline at 31.2 (μg / mL). The concentration unit of the added components is μg / mL in all graphs. The vertical axis indicates "% of control".

[0049]

Table 1

[0050] For Terminalia, a hot water extract (dry powder) of the fruit was used. For rice bran, a commercially available product was used. For Gynura procumbens, a dry pulverized powder of the leaves was used. For acai berries, a dry powder of commercially available fruits 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 rhizome of ginger was used. For pepper, a 100% ethanol extract of black pepper was used. For mugwort, a finely pulverized powder of fresh leaves was used. For caffeine, commercially available caffeine was used.

[0051]

Table 2

[0052]

Table 3

[0053]

Table 4

[0054]

Table 5

[0055] As shown in Tables 1 to 5 and FIGS. 1 to 13, by combining citrulline with specific other components of the present invention, the production amount of NO increased synergistically. Therefore, according to the blood flow improving composition of the present invention, the dilation of blood vessels is promoted, and the improvement of blood flow can be effectively achieved.

[0056] [Example 2] (Manufacture of Tablets)

[0057] Six tablets (7200 mg) of tablets composed of the following components were manufactured. Reduced maltose 5% by mass Citrulline 80% by mass Ginger extract 4% by mass Black pepper extract 2% 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 Shellac 1% by mass

[0058] The above tablets are taken with water in two or three divided doses a day.

[0059] [Example 3] (Manufacture of Capsules) The following mixture was encapsulated in soft capsules to manufacture capsules.

[0060] Citrulline 200 mg Ground black ginger 100 mg Maltose 50 mg Silicon dioxide 10 mg Niacin 5 mg Vitamin B1 5 mg Vitamin B2 5 mg Leucine 2.5 mg Tyrosine 2.5 mg Valine 2.5 mg Iron chloride 1 mg

[0061] The above capsules are taken with water in eight divided doses of 2 to 4 times a day.

[0062] [Example 4] (Manufacture of Granules) The following components were mixed to manufacture granules (5000 mg) by a conventional method.

[0063] Citrulline 3000 mg Terminalia bellirica powder 400 mg Reduced palatinose 500 mg Silicon dioxide 200 mg Sucrose fatty acid ester 50 mg Inositol 25 mg Biotin 10 mg Zinc gluconate 10 mg Magnesium chloride 5 mg Threonine 5 mg Tryptophan 2.5 mg Starch remainder

[0064] [Example 5] (Manufacture of instant powder) The following components were mixed and an instant powder (10 g) was manufactured by a conventional method.

[0065] Trehalose 0.1 g Reduced palatinose 0.1 g Calcium stearate 2 g Black pepper extract (dry powder) 1 g Citrulline 1 g Gallic acid 0.02 g Glutamine 0.01 g Zinc gluconate 0.001 g Iron chloride 0.001 g Water-soluble cellulose remainder

[0066] [Example 6] (Manufacture of liquid preparation) A liquid preparation (500 mL) consisting of the following components was manufactured. Aronia berry extract 3000 mg Trehalose 250 mg Citrulline 300 mg Vitamin K 150 mg Calcium chloride 50 mg Valine 25 mg Leucine 25 mg Isoleucine 25 mg Phenylalanine 10 mg 10 mg of proline 500 mg of vitamin C 120 mg of vitamin A 60 mg of vitamin B1 60 mg of vitamin B2 50 mg of zinc gluconate Remaining amount of water

Industrial Applicability

[0067] 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

[Claim 1] A composition comprising citrulline and at least one selected from the group consisting of zinc, copper, molybdenum and chromium.

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