JP2022173468A - Bloodstream ameliorating composition - Google Patents
Bloodstream ameliorating composition Download PDFInfo
- Publication number
- JP2022173468A JP2022173468A JP2022156948A JP2022156948A JP2022173468A JP 2022173468 A JP2022173468 A JP 2022173468A JP 2022156948 A JP2022156948 A JP 2022156948A JP 2022156948 A JP2022156948 A JP 2022156948A JP 2022173468 A JP2022173468 A JP 2022173468A
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- Prior art keywords
- present
- citrulline
- composition
- vitamin
- blood flow
- Prior art date
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Images
Abstract
Description
本発明は、血流改善効果を有する組成物に係り、詳しくは、シトルリン及び特定の他の成分を有効成分とする組成物に関する。 TECHNICAL FIELD The present invention relates to a composition having an effect of improving blood flow, and more particularly to a composition containing citrulline and specific other ingredients as active ingredients.
現代社会においては、運動不足やストレスによる自律神経失調等の様々な要因から、血液の循環（血流）の不調が問題となることが多い。この血流の不調（血流量の低下）は、頭痛、肩凝り、肌のくすみ、冷え性、むくみ等の様々な症状を引き起こすため、健康上、美容上の観点から、血流量を増加させ、血流を改善する方策が求められている。 In modern society, poor blood circulation (blood flow) is often a problem due to various factors such as autonomic imbalance due to lack of exercise and stress. This poor blood flow (decreased blood flow) causes various symptoms such as headaches, stiff shoulders, dull skin, sensitivity to cold, and swelling. Measures to improve flow are required.
このような血流改善のための組成物として、例えば、ヒソップ抽出物（特許文献１参照）や、カシス濃縮物とアミノ酸または有機酸を含む組成物（特許文献２参照）や、カモミール抽出エキス（特許文献３参照）等が提案されている。 Examples of such compositions 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 (see Patent Document 2). See Patent Document 3) and the like have been proposed.
一方、本件出願人は、松樹皮抽出物と黒胡椒抽出物とを含有する血流改善用組成物（特許文献４参照）を提案している。 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).
本発明の課題は、高い血流改善効果を有する組成物を提供することにある。 An object of the present invention is to provide a composition having a high effect of improving blood flow.
本発明者らは、シトルリンの血流改善能について鋭意調査・研究したところ、シトルリンと特定の他の成分とを組み合わせることにより、高い血流改善効果が得られることを見いだし、本発明を完成するに至った。すなわち、シトルリンと、血流改善能がほとんどないか、その能力が小さい特定の他の成分を組み合わせることにより、血流改善能を相乗的に向上させることができることを見いだした。 The present inventors have extensively investigated and researched the ability of citrulline to improve blood flow, and have found that a combination of citrulline and specific other ingredients can provide a high blood flow improvement effect, and have completed the present invention. reached. That is, the present inventors have found that by combining citrulline with other specific components that have little or no blood flow improving ability, the blood flow improving ability can be synergistically improved.
すなわち、本発明は、シトルリンと、下記（ａ）～（ｅ）からなる群より選ばれる少なくとも１種の成分とを有効成分として含有することを特徴とする組成物に関する。
（ａ）ターミナリア、稲、マキベリー、黒ショウガ、ショウガ、及びコショウから選ばれる少なくとも１種の植物素材
（ｂ）麦芽糖、トレハロース、還元パラチノース、還元麦芽糖、ステアリン酸カルシウム、及びシェラックから選ばれる少なくとも１種の機能性添加剤
（ｃ）ロイシン、メチオニン、フェニルアラニン、プロリン、セリン、トレオニン、トリプトファン、チロシン、及びバリンから選ばれる少なくとも１種のアミノ酸
（ｄ）没食子酸
（ｅ）ビタミンＡ、ビタミンＢ１、ビタミンＢ２、ビタミンＣ、パントテン酸ナトリウム、ナイアシン、葉酸、ビオチン、ビタミンＫ、イノシトール、カルシウム、亜鉛、鉄、銅、セレン、モリブデン、マグネシウム、及びクロムから選ばれる少なくとも１種のビタミン・ミネラル類
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 selected from maltose, trehalose, reduced palatinose, reduced maltose, calcium stearate, and shellac Functional additive (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/mineral selected from vitamin C, sodium pantothenate, niacin, folic acid, biotin, vitamin K, inositol, calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium
。
本発明の組成物は、シトルリンと（ａ）～（ｅ）からなる群より選ばれる少なくとも１種の成分とからなる有効成分を添加して得たものであってもよい。
.
The composition of the present invention may be obtained by adding an active ingredient consisting of citrulline and at least one ingredient selected from the group consisting of (a) to (e).
本発明の組成物において、シトルリン及び他の有効成分の配合質量比は、０．５：１～７０：１の範囲であることが好ましい。
また、本発明の組成物は、錠剤、カプセル剤、粉末剤、顆粒剤、又は液剤であることが好ましい。
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.
Also, the composition of the present invention is preferably a tablet, capsule, powder, granule, or liquid.
また、本発明は、上記本発明の組成物を摂取させることを特徴とする血流改善方法（ただし、医療行為を除く）に関する。 The present invention also relates to a method for improving blood flow (excluding medical practice), which comprises ingesting the composition of the present invention.
本発明の組成物によれば、血流量を増加させ、高い血流改善効果を得ることができる。 According to the composition of the present invention, it is possible to increase blood flow and obtain a high effect of improving blood flow.
本発明の組成物は、シトルリンと、下記（ａ）～（ｅ）からなる群より選ばれる少なくとも１種の成分（以下、他成分ということがある）とを有効成分として含有することを特徴とする。シトルリンと共に用いられる下記（ａ）～（ｅ）の成分は、１種単独（例えば（ａ）成分）で用いてもよいし、２種以上組み合わせて用いてもよい。他成分を２種以上組み合せて用いる場合、シトルリンと相乗効果の高い他成分同士を組み合わせることが好ましい。 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. do. The following components (a) to (e) used together with citrulline may be used singly (for example, component (a)), or two or more may be used in combination. When two or more other components are used in combination, it is preferable to combine citrulline with other components having a high synergistic effect.
本発明の組成物（血流改善組成物）は、かかる有効成分の組合せの相乗効果により、より有効に、血管周辺の筋肉を弛緩させて血管を拡張し、血流量を増加させることができ、頭痛、肩凝り、肌のくすみ、冷え症、勃起不全等の症状を効果的に予防ないし改善することができる。 The composition of the present invention (blood flow improving composition) can more effectively relax muscles around blood vessels, dilate blood vessels, and increase blood flow due to the synergistic effect of the combination of such active ingredients. It can effectively prevent or improve symptoms such as headache, stiff shoulders, dull skin, sensitivity to cold and erectile dysfunction.
［シトルリン］
本発明の血流改善組成物の有効成分となるシトルリンとしては、Ｌ－シトルリンであっても、Ｄ－シトルリンであってもよいが、Ｌ－シトルリンであることが好ましい。シトルリンは、化学合成により得られたもの、発酵に得られたもの等、その製造方法は問わない。また、シトルリンは、塩の形態であってもよく、塩としては、薬学的に許容される塩であれば特に制限されるものではなく、例えば、無機酸塩、有機酸塩、金属塩、アンモニウム塩を挙げることができる。シトルリンは、医薬品、試薬等として市販されており、これらの市販品を用いることができる。
[Citrulline]
Citrulline, which is the active ingredient of the composition for improving blood flow of the present invention, may be L-citrulline or D-citrulline, but L-citrulline is preferred. Citrulline can be produced by any method, such as chemical synthesis or fermentation. In addition, 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. Examples include inorganic acid salts, organic acid salts, metal salts, ammonium Mention may be made of salt. Citrulline is commercially available as pharmaceuticals, reagents, etc., and these commercial products can be used.
［他成分］
（ａ）植物素材
本発明の血流改善組成物においては、シトルリンと共に、有効成分として、ターミナリア、稲、マキベリー、黒ショウガ、ショウガ、及びコショウから選ばれる少なくとも１種の植物素材を用いることが好ましい。
[Other ingredients]
(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 terminalia, rice, maqui berry, black ginger, ginger, and pepper as an active ingredient together with citrulline. .
これらの植物素材は、葉、茎、根、花、実、幹、枝等、植物のいずれの部位であってもよく、植物素材そのもの（乾燥物を含む）の他、その粉砕物、搾汁、抽出物等の植物素材処理物を用いることができる。粉砕物としては、粉末、顆粒等が挙げられる。絞汁や抽出物は、液状であってもよいが、ペースト状や乾燥粉末として用いることもできる。抽出物は、適当な溶媒を用いて抽出することに得ることができ、溶媒としては、例えば、水（温水、熱水）、エタノール、含水エタノールを用いることができる。これらの植物素材は、市販されているものを使用することができる。 These plant materials may be any part of a plant such as leaves, stems, roots, flowers, fruits, trunks, branches, etc. In addition to the plant materials themselves (including dried products), their pulverized products and squeezed juices , extracts and other processed plant materials can be used. Powders, granules and the like can be mentioned as pulverized products. The squeezed juice or extract may be in liquid form, but may also be used in the form of paste or dry powder. The extract can be obtained by extraction using a suitable solvent, and examples of solvents that can be used include water (hot water, hot water), ethanol, and hydrous ethanol. Commercially available products can be used as these plant materials.
ターミナリアとしては、例えば、Terminalia bellirica（belerica）、Terminalia catappa、Terminalia tomentosa、Terminalia citrina、Terminalia phellocarpa、Terminalia copelandii、Terminalia brassi、Terminalia ivorensis、Terminalia superba、Terminalia arjuna、Terminalia chebula等を挙げることができ、これらの中でも、Terminalia bellirica（belerica）、Terminalia chebulaが好ましい。本発明の植物素材として用いる部位としては、果実が好ましい。 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, and Terminalia chebula. Among them, Terminalia bellirica (belerica) and Terminalia chebula are preferable. A fruit is preferable as the part used as the plant material of the present invention.
稲は、イネ科イネ属の植物である。本発明の植物素材として用いる部位としては、玄米の外皮や胚が好ましく、具体的には、玄米を精白する際に副産物として得られる米ぬかを用いることが好ましい。稲の種類としては、特に制限はなく、ジャポニカ種、インディカ種等を挙げることができる。 Rice is a plant belonging to the genus Poaceae. The part used as the plant material of the present invention is preferably the husk or embryo of brown rice. Specifically, it is preferable to use rice bran obtained as a by-product when brown rice is polished. The type of rice is not particularly limited, and includes japonica, indica, and the like.
マキベリーは、チリのパタゴニアを原産地とするポルトノキ科の植物であり、学術名は、Aristotellia chilensisである。本発明の植物素材として用いる部位としては、果実が好ましい。 Maqui berry is a plant of the Portunaceae family native to Patagonia, Chile, and its scientific name is Aristotellia chilensis. A fruit is preferable as the part used as the plant material of the present invention.
黒ショウガは、学名をＫａｅｍｐｆｅｒｉａ Ｐａｒｖｉｆｌｏｒａといい、東南アジアに自生するショウガ科バンウコン属の植物である。本発明の植物素材として用いる部位としては、根茎が好ましい。 Black ginger, whose scientific name is Kaempferia Parviflora, is a plant of the Zingiberaceae family and the genus Zingiberum, which grows naturally in Southeast Asia. A rhizome is preferable as the part used as the plant material of the present invention.
ショウガは、ショウガ科ショウガ属の植物であり、例えば、三州生姜、黄生姜、金時生姜、谷中生姜を挙げることができる。また、インドネシアやインドで栽培されている赤ショウガ（Zingiber officinale var. Rubra）も好ましく用いることができる。本発明の植物素材として用いる部位としては、根茎が好ましい。 Ginger is a plant belonging to the Zingiberaceae family Zingiber genus, and examples thereof include Sanshu ginger, yellow ginger, Kintoki ginger, and Yanaka ginger. Red ginger (Zingiber officinale var. Rubra) cultivated in Indonesia and India can also be preferably used. A rhizome is preferable as the part used as the plant material of the present invention.
コショウは、コショウ科の植物（Ｐｉｐｅｒ ｎｉｇｒｕｍ）であり、本発明の植物素材として用いる部位としては、果実が好ましい。収穫のタイミング等から、黒コショウ、白コショウ、赤コショウ等の種類が存在し、いずれの種類であってもよいが、黒コショウが好ましい。黒コショウは、コショウの木から取れた未熟な実を乾燥させたものであり、辛味成分ピペリンが含まれている。本発明のコショウとしては、このピペリンを含有するものが好ましい。 Pepper is a plant of the pepper family (Piper nigrum), and the fruit is preferable as the part used as the plant material of the present invention. There are various types of pepper, such as black pepper, white pepper, and red pepper, depending on the timing of harvesting. Black pepper is the dried unripe fruit of the pepper tree and contains the pungent component piperine. The pepper of the present invention preferably contains this piperine.
（ｂ）機能性添加剤
本発明の血流改善組成物においては、シトルリンと共に、有効成分として、麦芽糖、トレハロース、還元パラチノース、還元麦芽糖、ステアリン酸カルシウム、及びシェラックから選ばれる少なくとも１種の機能性添加剤を用いることが好ましい。
(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 an active ingredient together with citrulline. It is preferred to use agents.
（ｃ）アミノ酸
本発明の血流改善組成物においては、シトルリンと共に、有効成分として、ロイシン、メチオニン、フェニルアラニン、プロリン、セリン、トレオニン、トリプトファン、チロシン、及びバリンから選ばれる少なくとも１種のアミノ酸（塩を含む）を用いることが好ましい。塩としては、例えば、ナトリウム塩、塩酸塩等を挙げることができる。
(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 is used as an active ingredient. including) is preferably used. Examples of salts include sodium salts, hydrochlorides, and the like.
（ｄ）没食子酸
本発明の血流改善組成物においては、シトルリンと共に、有効成分として、没食子酸を用いることが好ましい。
(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）ビタミン・ミネラル類
本発明の血流改善組成物においては、シトルリンと共に、有効成分として、ビタミンＡ、ビタミンＢ１、ビタミンＢ２、ビタミンＣ、パントテン酸ナトリウム、ナイアシン、葉酸、ビオチン、ビタミンＫ、イノシトール、カルシウム、亜鉛、鉄、銅、セレン、モリブデン、マグネシウム、及びクロムから選ばれる少なくとも１種のビタミン・ミネラル類を用いることが好ましい。なお、本発明のミネラル類としてのカルシウム、亜鉛、鉄、銅、セレン、モリブデン、マグネシウム、及びクロムは、これらの金属を含む化合物の形態を含む。
(e) Vitamins and minerals In the blood flow improving composition of the present invention, along with citrulline, 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/mineral selected from inositol, calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium. Calcium, zinc, iron, copper, selenium, molybdenum, magnesium, and chromium as minerals in the present invention include compounds containing these metals.
本発明の血流改善組成物は、血流改善作用を有する血流改善剤として用いることができ、かかる血流改善剤は、シトルリン及び所定の他成分を含有し、血流改善に用いられる点において、製品として他の製品と区別することができるものであれば特に制限されるものではない。例えば、本発明に係る製品の本体、包装、説明書、宣伝物のいずれかに血流改善作用の機能がある旨を表示したものが本発明の範囲に含まれる。例えば、医薬品（医薬部外品を含む）や、特定保健用食品、栄養機能食品、機能性表示食品等の所定機関より効能の表示が認められた機能性食品などのいわゆる健康食品や、飼料等を挙げることができる。いわゆる健康食品においては、「めぐりを良くする」、「冷えを改善する」、「むくみが気になる方に」、「肌の色が気になる方に」、「目のくまが気になる方に」、「血管機能を高める」、「血管のしなやかさを高める」、「男性機能のサポートに」、「男性の活力に」等を表示したものを例示することができる。本発明の血流改善剤は、上記の効果が気になる人であれば性別や年齢に関係なく摂取することができるが、本発明の血流改善剤の効果をより有効に享受することができることから、疾病者を除く健常者が摂取することが望ましく、また、上記の悩みを持つ高齢者が摂取することが望ましい。また、冷えの改善効果や男性機能の改善が得られることから、夜に摂取することが望ましい。 The blood flow-improving composition of the present invention can be used as a blood flow-improving agent having a blood flow-improving action, and such a blood flow-improving agent contains citrulline and other predetermined ingredients and is used for blood flow improvement. , the product is not particularly limited as long as it can be distinguished from other products. For example, the scope of the present invention includes any product body, package, manual, or promotional material indicating that it has a function of improving blood flow. For example, pharmaceuticals (including quasi-drugs), so-called health foods such as foods for specified health uses, foods with nutrient function claims, functional foods whose efficacy has been approved by designated organizations, feeds, etc. can be mentioned. In the so-called health food, "Improve circulation", "Improve coldness", "For those who are concerned about swelling", "For those who are concerned about skin color", "For those who are concerned about dark circles" Examples include those labeled with words such as "towards", "improves vascular function", "improves suppleness of blood vessels", "supports male function", and "helps male vitality". The blood flow improving agent of the present invention can be ingested regardless of gender or age if the person is concerned about the above effects. Therefore, it is desirable that healthy people excluding sick people take it, and it is desirable that elderly people who have the above-mentioned problems take it. In addition, it is desirable to take it at night because it has the effect of improving coldness and improving male function.
本発明の血流改善組成物の形態としては、例えば、錠剤、カプセル剤、粉末剤、顆粒剤、液剤、粒状剤、棒状剤、板状剤、ブロック状剤、固形状剤、丸状剤、ペースト状剤、クリーム状剤、カプレット状剤、ゲル状剤、チュアブル状剤、スティック状剤等を挙げることができる。これらの中でも、錠剤、カプセル剤、粉末剤、顆粒剤、液剤の形態が特に好ましい。具体的には、サプリメントや、ペットボトル、缶、瓶等に充填された容器詰飲料や、水（湯）、牛乳、果汁、青汁等に溶解して飲むためのインスタント粉末飲料、インスタント顆粒飲料を例示することができる。これらは食事の際などに手軽に飲用しやすく、また嗜好性を高めることができるという点で好ましい。 Forms of the composition for improving blood flow of the present invention include, for example, tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, Examples include pastes, creams, caplets, gels, chewables, sticks and the like. Among these, tablets, capsules, powders, granules and liquids are particularly preferred. Specifically, supplements, packaged beverages filled in PET bottles, cans, bottles, etc., instant powdered beverages and instant granule beverages for dissolving in water (hot water), milk, fruit juice, green juice, etc. can be exemplified. These are preferable in that they are easy to drink with meals and can improve palatability.
本発明の血流改善組成物におけるシトルリン及び他成分（有効成分）の含有量としては、その効果の奏する範囲で適宜含有させればよい。 The contents of citrulline and other ingredients (active ingredients) in the blood flow improving composition of the present invention may be appropriately contained within the range in which the effects thereof are exhibited.
一般的には、本発明の血流改善組成物が医薬品やサプリメント（錠剤，カプセル剤）の場合には、有効成分が乾燥質量換算で全体の０．０００１～１００質量％含まれていることが好ましく、０．１～８５質量％含まれていることがより好ましく、０．５～７０質量％含まれていることがさらに好ましい。 In general, when the composition for improving blood flow of the present invention is a drug or supplement (tablets, capsules), the active ingredient should be contained in an amount of 0.0001 to 100% by mass in terms of dry mass of the whole. It is preferably contained in an amount of 0.1 to 85% by mass, more preferably 0.5 to 70% by mass.
本発明の血流改善組成物が容器詰飲料（液剤）である場合には、有効成分が乾燥質量換算で全体の０．０００１～１５質量％含まれていることが好ましく、０．００１～１２．５質量％含まれていることがより好ましく、０．０１～１０質量％含まれていることがさらに好ましい。 When the composition for improving blood flow of the present invention is a packaged beverage (liquid formulation), the content of the active ingredient in terms of dry mass is preferably 0.0001 to 15% by mass, preferably 0.001 to 12%. It is more preferably contained in an amount of 0.5% by mass, and more preferably in an amount of 0.01 to 10% by mass.
また、本発明の血流改善組成物がインスタント粉末飲料（粉末剤）、インスタント顆粒飲料（顆粒剤）である場合には、有効成分が乾燥質量換算で全体の０．００１～８０質量％含まれていることが好ましく、０．００５～７０質量％含まれていることがより好ましく、０．１～６０質量％含まれていることがさらに好ましい。 In addition, when the composition for improving blood flow of the present invention is an instant powdered beverage (powder) or an instant granular beverage (granules), the active ingredient is contained in an amount of 0.001 to 80% by mass in terms of dry mass of the whole. It is preferably contained in an amount of 0.005 to 70% by mass, more preferably 0.1 to 60% by mass.
本発明の効果をより有効に発揮させるためには、有効成分が乾燥質量換算で本発明の血流改善組成物全体（水分を除く）の８０％以上含まれていることが好ましく、９０％以上含まれていることがより好ましく、９５％以上含まれていることがさらに好ましく、１００％であることが特に好ましい。さらに、本発明の血流改善組成物が成分（ａ）～（ｅ）のいずれかを含有する場合、その含有される成分は、本発明における有効成分のみで構成されることが好ましい。すなわち、本発明の血流改善組成物が例えば成分（ａ）（植物素材）を含む場合には、ターミナリア、稲、マキベリー、黒ショウガ、ショウガ、コショウ以外の植物素材を含まないように構成することが好ましい。 In order to exhibit the effect of the present invention more effectively, the active ingredient is preferably contained in an amount of 80% or more, and preferably 90% or more, of the entire composition for improving blood flow (excluding water) in terms of dry mass. It is more preferably contained, more preferably 95% or more, and particularly preferably 100%. Furthermore, when the composition for improving blood flow of the present invention contains any one of components (a) to (e), it is preferable that the contained components consist only of the active ingredients of the present invention. That is, when the composition for improving blood flow of the present invention contains, for example, component (a) (plant material), it should be configured so as not to contain plant materials other than terminalaria, rice, maqui berry, black ginger, ginger and pepper. is preferred.
本発明の血流改善組成物の摂取量としては特に制限はないが、本発明の効果をより顕著に発揮させる観点から、１日当たりの有効成分の摂取量が、２００ｍｇ／日以上となるように摂取することが好ましく、４００ｍｇ／日以上となるように摂取することがより好ましく、６００ｍｇ／日以上となるように摂取することがさらに好ましい。その上限は特に制限されないが、例えば、１０ｇ／日であり、好ましくは８ｇ／日である。 The amount of intake of the composition for improving blood flow of the present invention is not particularly limited, but from the viewpoint of exhibiting the effects of the present invention more remarkably, the daily intake of the active ingredient should be 200 mg/day or more. It is preferably ingested, more preferably 400 mg/day or more, and even more preferably 600 mg/day or more. Although the upper limit is not particularly limited, it is, for example, 10 g/day, preferably 8 g/day.
本発明の血流改善組成物は、1日の摂取量が前記摂取量となるように、１つの容器に、又は例えば２～３の複数の容器に分けて、1日分として収容することができる。 The composition for improving blood flow of the present invention can be contained in one container, or divided into a plurality of containers, for example, 2 to 3, so that the daily intake is the above-mentioned intake, as a daily dose. can.
シトルリン及び他成分の配合質量比としては、乾燥質量換算で、０．５：１～７０：１の範囲であることが好ましく、０．７５：１～６０：１の範囲であることがより好ましく、１：１～６０：１の範囲であることがさらに好ましく、１：１～５０：１の範囲であることが特に好ましい。シトルリン及び他成分の配合比が、上記範囲であることにより、本発明の効果をより有効に発揮することができる。 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 in terms of dry mass. , more preferably in the range of 1:1 to 60:1, particularly preferably in the range of 1:1 to 50:1. When the compounding ratio of citrulline and other components is within the above range, the effects of the present invention can be exhibited more effectively.
本発明の血流改善組成物は、必要に応じて、経口用として許容される有効成分以外の成分を添加して、公知の製剤方法によって製造することができる。 The blood flow improving composition of the present invention can be produced by a known formulation method by adding ingredients other than orally acceptable active ingredients, if necessary.
また、本発明の血流改善組成物としては、有効成分を含有する血流改善食品の他、食品に対して有効成分を添加して得た血流改善食品を挙げることができ、例えば、通常の食品に比して本発明の有効成分含有量を増加させた食品や、本発明の有効成分を通常含まない食品に対して有効成分を添加した食品を挙げることができる。有効成分の添加は、それぞれの成分を別々に添加してもよいし、同時に添加してもよく、また、有効成分以外の他の成分と共に添加してもよい。 Examples of the blood flow-improving composition of the present invention include blood flow-improving foods containing active ingredients and blood flow-improving foods obtained by adding active ingredients to foods. Foods having an increased content of the active ingredient of the present invention compared to the food of No. 1, and foods to which the active ingredient of the present invention is added to foods that normally do not contain the active ingredient of the present invention can be mentioned. When adding the active ingredients, each ingredient may be added separately, may be added at the same time, or may be added together with other ingredients other than the active ingredient.
本発明の血流改善食品としては、例えば、炭酸飲料、栄養飲料、果実飲料、乳酸飲料、スムージー、青汁等の飲料；アイスクリーム、アイスシャーベット、かき氷等の冷菓；そば、うどん、はるさめ、中華麺、即席麺等の麺類；飴、キャンディー、ガム、チョコレート、錠菓、スナック菓子、ビスケット、ゼリー、ジャム、クリーム、焼き菓子、パン等の菓子類；かまぼこ、ハム、ソーセージ等の水産・畜産加工食品；加工乳、発酵乳、ヨーグルト等の乳製品；サラダ油、てんぷら油、マーガリン、マヨネーズ、ショートニング、ホイップクリーム、ドレッシング等の油脂及びその加工食品；ソース、醤油等の調味料；カレー、シチュー、親子丼、お粥、雑炊、中華丼、かつ丼、天丼、牛丼、ハヤシライス、オムライス、おでん、マーボドーフ、餃子、シューマイ、ハンバーグ、ミートボール、各種ソース、各種スープ等のレトルトパウチ食品などを挙げることができる。 Examples of blood flow-improving foods of the present invention include carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, smoothies, green juices, and other beverages; ice cream, ice sherbet, shaved ice, and other frozen desserts; Noodles such as noodles and instant noodles; Confectionery such as candies, candies, gums, chocolates, tablets, snacks, biscuits, jellies, jams, creams, baked goods, and bread; Processed marine and livestock foods such as fish cakes, hams, and sausages Dairy products such as processed milk, fermented milk, and yogurt; Fats and oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings, and their processed foods; Seasonings such as sauces and soy sauce; Curry, stew, oyakodon , porridge, rice porridge, Chinese rice bowl, katsudon, tempura rice bowl, beef bowl, hayashi rice, omelet rice, oden, mapo dofu, dumplings, shumai, hamburgers, meatballs, various sauces, various soups, and other retort pouch foods. .
本発明の血流改善方法としては、上記説明した本発明の血流改善組成物を摂取させることを特徴とするが、医療行為は含まれない。本発明の血流改善組成物は、上記の効果が気になる人であれば性別や年齢に関係なく摂取させることができるが、本発明の血流改善組成物の効果をより有効に享受することができることから、疾病者を除く健常者に摂取させることが望ましく、また、上記の悩みを持つ高齢者に摂取させることがさらに望ましい。また、冷えの改善効果や男性機能の改善が得られることから、夜に摂取させることが望ましい。本発明の方法としては、例えば、レストラン等の飲食店において、本発明の血流改善食品を提供することにより、血流の改善を図る方法を挙げることができる。 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 by people who are concerned about the above effects regardless of gender or age, and the effect of the blood flow-improving composition of the present invention can be more effectively enjoyed. Therefore, it is desirable to have healthy people excluding sick people take it, and it is more desirable to have elderly people who have the above-mentioned troubles take it. In addition, it is desirable to take it at night because it has the effect of improving coldness and improving male function. 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.
以下、本発明を実施例に基づき説明する。
［実施例１］
１．細胞培養
（１）３７℃、５％ＣＯ２インキュベーター内で、７５ｃｍ２フラスコを用いて、ブタ肺動脈血管内皮細胞（ＰＰＡＥＣ）を１０％ＦＢＳ－ＲＰＭＩ １６４０により培養した。
（２）トリプシン処理により浮遊させた細胞を７５ｃｍ２フラスコから９６ｗｅｌｌ ｐｌａｔｅの各ｗｅｌｌに１．０×１０４ｃｅｌｌｓ／ｗｅｌｌの細胞密度で播種した。
（３）３７℃、５％ＣＯ２インキュベーター内で４８時間前培養した。
（４）各ｗｅｌｌより培地を除去後、４％ＦＢＳ－αＭＥＭにて所定濃度に調製した被験物質含有培地を１００μＬずつ添加し、ＣＯ２インキュベーター内で２４時間培養した。
EXAMPLES The present invention will be described below based on examples.
[Example 1]
1. cell culture
(1) Porcine pulmonary artery endothelial cells (PPAEC) were cultured with 10% FBS-RPMI 1640 using a 75 cm 2 flask in a 37° C., 5% CO 2 incubator.
(2) Cells suspended by trypsin treatment were seeded from a 75 cm 2 flask to each well of a 96-well plate at a cell density of 1.0×10 4 cells/well.
(3) Precultured for 48 hours in a 37°C, 5% CO2 incubator.
(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 and cultured in a CO 2 incubator for 24 hours.
なお、シトルリンと他成分の併用サンプルについては、それぞれ２倍濃度の被験物質含有培地を５０μＬずつ添加することで目的の濃度とした。また、ｃｏｎｔｒｏｌについては、被験物質をＤＭＳＯに溶解したものに対しては０．２５％ＤＭＳＯ含有４％ＦＢＳ－αＭＥＭを用いて調製し、その他の被験物質に対しては４％ＦＢＳ－αＭＥＭを用いて調製した。 For the combined sample of citrulline and other components, 50 μL each of medium containing the test substance at twice the concentration was added to obtain the desired concentration. In addition, the control was prepared using 4% FBS-αMEM containing 0.25% DMSO for the test substance dissolved in DMSO, and 4% FBS-αMEM was used for the other test substances. was prepared.
シトルリンについては、市販のシトルリンを用いた。シトルリンと共に用いる他成分としては、表１～表５に示す物質を用いた。 As for citrulline, commercially available citrulline was used. As other components used together with citrulline, substances shown in Tables 1 to 5 were used.
２．ＮＯ産生量の評価
（１）２４時間培養後、培養上清５０μＬを１．５ｍＬサンプルチューブに回収し、Ｎ＝３のサンプルを混合した。
（２）４℃、２０００ｇで３分間遠心し、上清を別の１．５ｍＬエッペンチューブに移した。
（３）Ｎｉｔｒａｔｅ／Ｎｉｔｒｉｔｅ Ａｓｓａｙ Ｋｉｔ，Ｆｌｕｏｒｏｍｅｔｒｉｃ（Ｃａｙｍａｎ製）を用いて、（２）のサンプル中のＮＯ濃度（μＭ）を測定した。なお、血管内皮細胞から産生されるＮＯは、血管周辺の筋肉を弛緩させて血管を拡張する作用を有する。
（４）算出したＮＯ濃度をもとに「％ ｏｆ ｃｏｎｔｒｏｌ」を算出した。
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 mixed with N=3 samples.
(2) It was centrifuged at 4° C. and 2000 g for 3 minutes, and the supernatant was transferred to another 1.5 mL Eppendorf tube.
(3) Nitrate/Nitrite Assay Kit, Fluorometric (manufactured by Cayman) was used to measure the NO concentration (μM) in the sample of (2). NO produced from vascular endothelial cells has the effect of relaxing muscles around blood vessels and dilating blood vessels.
(4) "% of control" was calculated based on the calculated NO concentration.
％ ｏｆ ｃｏｎｔｒｏｌ
＝試料のＮＯ濃度（μＭ）／ｃｏｎｔｒｏｌのＮＯ濃度（μＭ）×１００
% of control
= NO concentration of sample (μM) / NO concentration of control (μM) × 100
その結果を表１～表５、及び図１～図１３に示す。各図は、左から、「コントロール（添加なし）」、「シトルリンの単独添加」、「他成分の単独添加」、「シトルリン＋他成分添加」の結果を表す。また、グラフ下部の説明における数値は、サンプル濃度を示し、例えば、図１の左上のグラフの「シトルリン_３１．２」は、シトルリン３１．２（μｇ／ｍＬ）を示す。添加成分の濃度単位は、すべてのグラフにおいて、μｇ／ｍＬである。縦軸は「％ ｏｆ ｃｏｎｔｒｏｌ」を示す。 The results are shown in Tables 1 to 5 and FIGS. 1 to 13. Each figure represents, from the left, the results of "control (no addition)", "single addition of citrulline", "single addition of other ingredients", and "addition of citrulline + other ingredients". Also, 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). Concentration units for added components are μg/mL in all graphs. The vertical axis indicates "% of control".
ターミナリアについては、果実の熱水抽出物（乾燥粉末）を用いた。
米ぬかについては、市販品を用いた。
長命草については、葉の乾燥粉砕末を用いた。
マキベリーについては、市販品の果実の乾燥粉末を用いた。
黒ショウガについては、黒ショウガの根茎の６０％エタノール抽出物（乾燥粉末）を用いた。
ショウガについては、ショウガの根茎の熱水抽出物（乾燥粉末）を用いた。
コショウについては、黒コショウの１００％エタノール抽出物を用いた。
ヨモギについては、生葉の微粉砕末を用いた。
カフェインについては、市販のカフェインを用いた。
For Terminalia, a hot water extract of fruit (dry powder) was used.
As for rice bran, a commercially available product was used.
For Chomeisou, dried powder of leaves was used.
For maqui berries, dry powder of commercially available fruit was used.
For black ginger, a 60% ethanol extract (dry powder) of black ginger rhizome was used.
For ginger, a hot water extract (dry powder) of ginger rhizome was used.
For pepper, a 100% ethanol extract of black pepper was used.
As for mugwort, fine pulverized powder of fresh leaves was used.
As for caffeine, commercially available caffeine was used.
表１～表５、及び図１～図１３に示すように、シトルリンと、本発明の特定の他成分を組み合わせることにより、ＮＯの産生量が相乗的に増加した。したがって、本発明の血流改善組成物によれば、血管の拡張が促進され、有効に血流の改善を図ることができる。 As shown in Tables 1-5 and FIGS. 1-13, the combination of citrulline and certain other ingredients of the present invention synergistically increased NO production. Therefore, the blood flow-improving composition of the present invention promotes dilation of blood vessels and effectively improves blood flow.
［実施例２］（錠剤の製造） [Example 2] (Production of tablets)
下記成分からなるタブレット６錠（７２００ｍｇ）を製造した。
還元麦芽糖 ５質量％
シトルリン ８０質量％
ショウガ抽出物 ４質量％
コショウ抽出物 ２質量％
ビタミンＣ １質量％
葉酸 １質量％
没食子酸 １質量％
セルロース ２質量％
二酸化ケイ素 ２質量％
ステアリン酸カルシウム １質量％
シェラック １質量％
Six tablets (7200 mg) were prepared from the following ingredients.
Reduced maltose 5% by mass
80% by mass of citrulline
Ginger extract 4% by mass
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
上記錠剤は一日に２、３回に分けて水と共に服用する。 Take the above tablets two or three times a day with water.
［実施例３］（カプセル剤の製造）
下記混合物をソフトカプセルに封入し、カプセル剤を製造した。
[Example 3] (Production of capsules)
The following mixture was encapsulated in soft capsules to produce capsules.
シトルリン ２００ｍｇ
黒ショウガ末 １００ｍｇ
麦芽糖 ５０ｍｇ
二酸化ケイ素 １０ｍｇ
ナイアシン ５ｍｇ
ビタミンＢ１ ５ｍｇ
ビタミンＢ２ ５ｍｇ
ロイシン ２．５ｍｇ
チロシン ２．５ｍｇ
バリン ２．５ｍｇ
塩化鉄 １ｍｇ
200 mg of citrulline
Black ginger powder 100mg
Maltose 50mg
Silicon dioxide 10mg
Niacin 5mg
Vitamin B1 5mg
Vitamin B2 5mg
Leucine 2.5mg
Tyrosine 2.5 mg
Valine 2.5 mg
1 mg iron chloride
上記カプセル剤は８錠を一日に２～４回に分けて水と共に服用する。 Take 8 capsules 2 to 4 times a day with water.
［実施例４］（顆粒剤の製造）
下記成分を混合して常法により顆粒剤（５０００ｍｇ）を製造した。
[Example 4] (Production of granules)
Granules (5000 mg) were prepared by a conventional method by mixing the following ingredients.
シトルリン ３０００ｍｇ
ターミナリアベリリカ末 ４００ｍｇ
還元パラチノース ５００ｍｇ
二酸化ケイ素 ２００ｍｇ
ショ糖脂肪酸エステル ５０ｍｇ
イノシトール ２５ｍｇ
ビオチン １０ｍｇ
グルコン酸亜鉛 １０ｍｇ
塩化マグネシウム ５ｍｇ
トレオニン ５ｍｇ
トリプトファン ２．５ｍｇ
デンプン 残部
Citrulline 3000mg
Terminalia berylica powder 400mg
Reduced Palatinose 500mg
Silicon dioxide 200mg
Sucrose fatty acid ester 50mg
Inositol 25mg
Biotin 10mg
Zinc gluconate 10mg
5 mg of magnesium chloride
Threonine 5mg
Tryptophan 2.5 mg
Starch remainder
［実施例５］（インスタント粉末剤の製造）
下記成分を混合して常法によりインスタント粉末（１０ｇ）を製造した。
[Example 5] (Production of instant powder)
An instant powder (10 g) was prepared by a conventional method by mixing the following ingredients.
トレハロース ０．１ｇ
還元パラチノース ０．１ｇ
ステアリン酸カルシウム ２ｇ
黒ショウガ抽出物（乾燥粉末） １ｇ
シトルリン １ｇ
没食子酸 ０．０２ｇ
グルタミン ０．０１ｇ
グルコン酸亜鉛 ０．００１ｇ
塩化鉄 ０．００１ｇ
水溶性セルロース 残部
Trehalose 0.1g
Reduced Palatinose 0.1g
2g calcium stearate
1 g of black ginger extract (dry powder)
1 g of citrulline
Gallic acid 0.02g
Glutamine 0.01g
Zinc gluconate 0.001g
Iron chloride 0.001g
water-soluble cellulose balance
［実施例６］（液剤の製造）
下記成分からなる液剤（５００ｍＬ）を製造した。
マキベリー抽出物 ３０００ｍｇ
トレハロース ２５０ｍｇ
シトルリン ３００ｍｇ
ビタミンＫ １５０ｍｇ
塩化カルシウム ５０ｍｇ
バリン ２５ｍｇ
ロイシン ２５ｍｇ
イソロイシン ２５ｍｇ
フェニルアラニン １０ｍｇ
プロリン １０ｍｇ
ビタミンＣ ５００ｍｇ
ビタミンＡ １２０ｍｇ
ビタミンＢ１ ６０ｍｇ
ビタミンＢ２ ６０ｍｇ
グルコン酸亜鉛 ５０ｍｇ
水 残量
[Example 6] (manufacture of liquid agent)
A liquid formulation (500 mL) was prepared from the following components.
Maqui berry extract 3000mg
Trehalose 250mg
300 mg of citrulline
Vitamin K 150mg
50 mg of calcium chloride
Valine 25mg
Leucine 25mg
Isoleucine 25mg
10 mg of phenylalanine
Proline 10mg
Vitamin C 500mg
Vitamin A 120mg
Vitamin B1 60mg
Vitamin B2 60mg
Zinc gluconate 50mg
remaining water
本発明の組成物は、血流を改善する効果を有し、経口剤として用いることができることから、本発明の産業上の有用性は高い。 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）稲、マキベリー、及びコショウから選ばれる少なくとも１種の植物素材
（ｂ）麦芽糖、トレハロース、還元パラチノース、還元麦芽糖、ステアリン酸カルシウム、及びシェラックから選ばれる少なくとも１種の機能性添加剤
（ｃ）ロイシン、メチオニン、フェニルアラニン、セリン、及びバリンから選ばれる少なくとも１種のアミノ酸
（ｄ）没食子酸
（ｅ）ビタミンＡ、ビタミンＢ１、ビタミンＢ２、ビタミンＣ、パントテン酸ナトリウム、ナイアシン、葉酸、ビオチン、ビタミンＫ、イノシトール、カルシウム、亜鉛、鉄、銅、セレン、モリブデン、マグネシウム、及びクロムから選ばれる少なくとも１種のビタミン・ミネラル類 A composition comprising citrulline and at least one component selected from the group consisting of (a) to (e) below as active ingredients.
(a) at least one plant material selected from rice, maqui berry, 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, serine, and valine (d) gallic acid (e) 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
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