JP5294149B2 - グルタミン含有血流増加用組成物 - Google Patents
グルタミン含有血流増加用組成物 Download PDFInfo
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- JP5294149B2 JP5294149B2 JP2008536448A JP2008536448A JP5294149B2 JP 5294149 B2 JP5294149 B2 JP 5294149B2 JP 2008536448 A JP2008536448 A JP 2008536448A JP 2008536448 A JP2008536448 A JP 2008536448A JP 5294149 B2 JP5294149 B2 JP 5294149B2
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- JP
- Japan
- Prior art keywords
- blood flow
- glutamine
- composition
- increasing blood
- body weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
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- A—HUMAN NECESSITIES
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- A23K20/142—Amino acids; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
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Description
こうした血流増加剤としてカルシウム拮抗剤や細胞呼吸賦活剤、鎮けい剤、生体内酵素などが用いられてきた。
これまでの研究によりアルギニンは血管を拡張させることが知られており、その作用機構として、血管内皮細胞に発現する一酸化窒素合成酵素が血管を拡張させる一酸化窒素をアルギニンから合成することが明らかにされている。外部から投与されたアルギニンはただちに一酸化窒素の合成を引き起こし、この作用による血管の拡張が生じるが、食餌由来のアルギニンは通常こうした作用を示さない(非特許文献3)。
こうしたアルギニン摂取の作用は広く知られていたが、従来はアルギニンによる血管の拡張は血流の増加と同時に血圧の低下も生じさせると考えられてきた。例えば平均体重78キログラムのヒトに30グラムないし6グラムのアルギニンを静脈投与した検討では、30グラムのアルギニン投与では血圧の低下及び血管抵抗の低下が生じたのに対して6グラムのアルギニン投与ではそのどちらも生じなかったことが報告されている(非特許文献4)。このほかにもアルギニンによる血流の増加は報告されているが、いずれの場合もアルギニン投与量が過大か、ポリフェノール類といった単独で血流増加作用を有する血流増加用組成物と併用する必要がある(非特許文献5、特許文献1、2)。このためアルギニン単独では血圧の低下を引き起こすことなく血流を増加させることは難しいと考えられてきた。こうした背景から発明者らのグループはアルギニン投与時の血流と血圧について詳細な調査を行い、血圧の低下を引き起こすことなく血流を増加させる投与法についての発明を完成させた。
すなわち本発明は、グルタミンを含有する血流増加用組成物であって、グルタミンを1回あたりの投与量が25mg/kg体重〜150mg/kg体重となる量で含有する前記血流増加用組成物を提供する。
本発明はまた、グルタミンのみからなる血流増加用組成物であって、グルタミンを1回あたりの投与量が25mg/kg体重〜150mg/kg体重となる量で含有する前記血流増加用組成物を提供する。
本発明はまた、上記血流増加用組成物を含有する、痴呆、冷え性、肩凝り、くすみ、肝機能低下、免疫低下を予防、軽減又は治療するための医薬組成物を提供する。
本発明はまた、グルタミンを1回あたりの投与量が25mg/kg体重〜150mg/kg体重となる量で含有する血流増加用食品を提供する。
本発明はまた、上記血流増加用組成物を含有する飼料を提供する。
本発明の血流増加用組成物におけるグルタミンの含有量は、1回あたりの投与量が25mg/kg体重〜150mg/kg体重、好ましくは50〜150mg/kg体重となる量である。
本発明の血流増加用組成物におけるグルタミンの含有量は、組成物を投与した際の血漿中遊離グルタミン濃度の上昇が血漿1ミリリットルあたり15ミリグラムから180ミリグラム、好ましくは25ミリグラムから180ミリグラム、より好ましくは50ミリグラムから180ミリグラム、更に好ましくは50ミリグラムから150ミリグラムの範囲となるような用量のグルタミンに相当するのが好ましく、本発明の1回あたりの投与量はこれを満足するものである。ここで、血漿中遊離グルタミン濃度は、グルタミン投与後、10分経過後の血漿を採取して、アミノ酸アナライザー(日立製作所製アミノ酸アナライザー、L8500)を用いることにより測定することができる。
本発明では、本発明の組成物を投与する前の血流に対して20%以上血流が増加したとき血流増加と判断する。これは、対照自体が19%未満の血流の変動があることに起因している。
本発明において使用できるグルタミン酸としては、L体グルタミン酸及び構成アミノ酸としてL体グルタミン酸を含むペプチドがあげられる。該酸は、ナトリウム、カリウム等のアルカリ金属及びカルシウム等のアルカリ土類金属、アルギニン及びリジン等の塩基性アミノ酸、トリエタノールアミン等のアミン類等と塩を形成してもよい。該酸はまた、アルコール類と誘導体を形成してもよく、該酸から構成される酸無水物、小麦グルテン加水分解物などのペプチド及び小麦グルテンなどのたんぱく質等の形態であってもよい。このうち、L体グルタミン酸が好ましい。
本発明の血流増加用組成物におけるグルタミンと、ピロリドンカルボン酸、ピロリドンカルボン酸塩およびピロリドンカルボン酸誘導体からなる群から選ばれるアミノ酸との配合比は、質量比にして1:4〜4:1、好ましくは1:2〜2:1とするのが好ましい。
このような比でグルタミンと、ピロリドンカルボン酸、ピロリドンカルボン酸塩およびピロリドンカルボン酸誘導体からなる群から選ばれるアミノ酸とを併有することにより、血流量が著しく増大するので好ましい。
本発明の血流増加用組成物は、医薬組成物形態の他、血流増加のために用いられるものである旨の表示を附した食品、健康食品、栄養補助食品(サプリメント)、栄養組成物又は飼料等の形態をとることもできる。投与量は、通常、投与対象の体重及び健康状態等に依存して変化するが、成人に使用する場合、グルタミンとして1日あたり好ましくは4.5g〜27g、より好ましくは9g〜27gである。製品の包装形態として、1単位包装当り1〜27g、例えば1g、2g、3g、4g、4.5g〜27gのいずれか1つの包装形態であることが可能である。包装形態1g、2g、3g、4gなどの場合は、1日のうちに、複数回、投与することができる。
本発明の医薬組成物は、更に、中枢神経用薬、末梢神経用薬、循環器用薬、ホルモン剤、抗ホルモン剤、ビタミン剤、滋養強壮薬、解毒剤、抗腫瘍剤、アレルギー用薬、生薬、漢方製剤、化学療法剤、生物学的製剤、診断用薬など医薬品として使用されている他の有効成分を含有することもできる。
本発明の医薬組成物は、経口的又は非経口的に、例えば経腸、経静脈投与することもできる。
本発明の食品は、更に、アミノ酸、ビタミン、卵殻カルシウム、パントテン酸カルシウム、その他のミネラル類、ローヤルゼリー、プロポリス、蜂蜜、食物繊維、アガリクス、キチン、キトサン、カプサイシン、ポリフェノール、カロテノイド、脂肪酸、ムコ多糖、補酵素、抗酸化物質などを配合することにより健康食品とすることもできる。
本発明の血流増加用組成物の製品形態には特別の制限は無く、通常用いられているアミノ酸の摂取できる形態であればいずれの形態でもよい。このような形態としては経口摂取であれば適当な賦形剤を使用した粉末、顆粒、タブレット、液体(飲料、ゼリー飲料)、キャンディ(チョコレート等)、あるいは上記1種あるいは2種のアミノ酸の単なる混合物を挙げることが出来る。また静脈投与であれば上記1種あるいは2種のアミノ酸を含有した輸液、水溶液、用時調製のためのアミノ酸粉末を挙げることが出来る。
試験例(ラットにグルタミンを経口投与した際の各種臓器の血流の変化量の確認)
(1)試験の概要:
(a)ラットを対象にグルタミン投与時の複数の臓器での毛細血管での血流の変化を測定した。
(b)体重400グラム前後のSD系雄ラットを対象とした。
(c)ラットをペントバルビタールで麻酔し、心臓左心室及び右足の大腿部にカテーテルを留置した。麻酔から回復させた後に経口ゾンデを用いて胃内にグルタミンを体重1キロあたりアミノ酸として50ミリグラムの用量で注入した。これらのアミノ酸液の投与の前後に頚動脈から左心室に留置したカテーテルから各々黄色及び赤色のマイクロスフィアを注入し、心臓から全身の臓器の毛細血管に分布したマイクロスフィア量を比較することにより各臓器のグルタミン投与前後の血流を比較した。また陰性対象群には蒸留水を投与した。
(e)以上の結果から、体重1キロ当たり50ミリグラムのグルタミンを投与したラットでは、腹部皮膚、脾臓、肝臓、心臓及び脳の毛細血管での血流の増加が顕著に認められており、本発明のグルタミン投与の効果は腹部皮膚、脾臓、肝臓、心臓及び脳において特に顕著であると考えられた。
(c)血流の測定:30分間のグルタミン投与の直前及び直後に黄色及び赤色マイクロスフィアを左心室内に留置したカテーテルより注入した。二度目のマイクロスフィア投与から十分な時間を置いた後にラットを安楽死させ、筋肉、消化管、肝臓、腎臓、脾臓、心臓、脳、脂肪組織、腹部皮膚を取り出したのちに、各臓器に含まれるマイクロスフィアを回収し、マイクロスフィア量から算出した血流の変化率を各臓器ごとに求めた。
(d)試験結果:グルタミン投与試験で観察された血流の変化を下記第2表にまとめた。
Claims (5)
- 有効成分としてグルタミンのみを含有する血流増加用組成物であって、グルタミンを1回あたりの投与量が25mg/kg体重〜150mg/kg体重となる量で含有する前記血流増加用組成物。
- 前記組成物が、グルタミンを1回あたりの投与量が50mg/kg体重〜150mg/kg体重となる量で含有する請求項1記載の血流増加用組成物。
- グルタミンが、L-グルタミン、L-グルタミン塩化物からなる群から選ばれる請求項1又は2記載の血流増加用組成物。
- 一単位包装当りグルタミンを、アミノ酸遊離体換算量で、1g〜27g含有することを特徴とする請求項1〜3のいずれか1項記載の血流増加用組成物。
- 請求項1〜4のいずれか1項記載の血流増加用組成物を含有する、痴呆、冷え性、肩凝り、くすみ又は筋疲労を予防、軽減又は治療するための医薬組成物。
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2007
- 2007-09-28 EP EP07828729A patent/EP2077110A4/en not_active Withdrawn
- 2007-09-28 JP JP2008536448A patent/JP5294149B2/ja active Active
- 2007-09-28 WO PCT/JP2007/068988 patent/WO2008038771A1/ja active Application Filing
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2009
- 2009-03-30 US US12/414,037 patent/US7829593B2/en active Active
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WO1995018608A1 (en) * | 1994-01-11 | 1995-07-13 | N.V. Nutricia | Method of treating disorders of the animal or human body by administering amino acids |
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JP2002045122A (ja) * | 2000-05-26 | 2002-02-12 | Ajinomoto Co Inc | 家畜用飼料 |
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JP5046174B2 (ja) * | 2005-03-31 | 2012-10-10 | 味の素株式会社 | アルギニン含有血流増加用組成物 |
Also Published As
Publication number | Publication date |
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US7829593B2 (en) | 2010-11-09 |
EP2077110A4 (en) | 2012-06-27 |
EP2077110A1 (en) | 2009-07-08 |
US20090209614A1 (en) | 2009-08-20 |
JPWO2008038771A1 (ja) | 2010-01-28 |
WO2008038771A1 (fr) | 2008-04-03 |
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