JP2006063003A - 形質転換増殖因子β抑制用組成物 - Google Patents
形質転換増殖因子β抑制用組成物 Download PDFInfo
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Abstract
【解決手段】 テアニンを有効成分とする組成物を投与することにより、血中及び脳精髄液中のTGF−βの上昇抑制効果が得られる。本願発明によれば、新規なTGF−β抑制用組成物の提供が可能となり、慢性糸球体腎炎、腎臓間質性線維症、糖尿病性腎症、肝線維症、肝硬変、肺繊維症、ケロイド、強皮症、動脈硬化、後部心筋梗塞、心臓性線維症、血管形成後再狭窄、急性巨核芽球性白血病、成人T細胞白血病、慢性疲労などの疾患や疲労一般などのTGF−β抑制活性に基づく予防効果又は治療効果に有用である。
【選択図】 なし
Description
本発明に用いられるテアニンとは、茶の葉に含まれているグルタミン酸誘導体で、茶の旨味の主成分であって、呈味を用途とする食品添加物として使用されている。本発明に用いられるテアニンの製造法としては、茶葉から抽出する方法、有機合成反応させてテアニンを得る方法(Chem.Pharm.Bull.,19(7)1301−1307(1971))、グルタミンとエチルアミンの混合物にグルタミナーゼを作用させてテアニンを得る方法(特公平7−55154号)、エチルアミンを含有する培地で茶の培養細胞群を培養し、培養細胞群中のテアニン蓄積量を増加させつつ培養細胞群の増殖促進を図る方法(特開平5−123166号)、また、特公平7−55154号、開平5−123166号におけるエチルアミンをエチルアミン塩酸塩などのエチルアミン誘導体に置き換えてテアニンを得る方法、茶葉から抽出する方法等がありいずれの方法でも良い。ここでいう茶葉とは、緑茶、ウーロン茶、紅茶等があげられる。このような方法により得られたテアニンは、L−体、D−体、DL−体いずれも使用可能であるが、中でもL−体は、食品添加物にも認められており、経済的にも利用しやすいため、本発明においては、L−体が好ましい。
本発明に係る組成物は、TGF−β抑制活性に基づく具体的な効果として、例えば慢性糸球体腎炎、腎臓間質性線維症、糖尿病性腎症、肝線維症、肝硬変、肺繊維症、ケロイド、強皮症、動脈硬化、後部心筋梗塞、心臓性線維症、血管形成後再狭窄、急性巨核芽球性白血病、成人T細胞白血病、慢性疲労などの疾患や一般的な疲労のTGF−β抑制活性に基づく予防効果又は治療効果を示す。
本発明に係る食品の形態としては、溶液、懸濁物、粉末、固体成形物等の形態であれば良く、特に限定するものではない。より具体的には、練り製品、大豆加工品、調味料、ムース、ゼリー、冷菓、飴、チョコレート、ガム、クラッカー、ケーキ、パン、スープ、コーヒー、ココア、紅茶、緑茶、ジュース、乳飲料、乳製品、酒、錠剤、カプセル、医薬品等が例示される。次に実施例によって本発明をさらに説明するが、本発明はこれらのみに限定されるものではない。
0.3Mグルタミン及び1.5M塩酸エチルアミンを0.05Mホウ酸緩衝液(pH11)中、0.3Uグルタミナーゼ(市販品)存在下にて、30℃、22時間反応させ225nmolのL−テアニンを得た。次いで、反応液をDowex 50×8、Dowex 1×2カラムクロマトグラフィー(共に室町化学工業(株)製)にかけ、これをエタノール処理することにより、反応液から目的物質を単離した。
茶(Camellia sinensis)の葉10kgを熱水で抽出後、カチオン交換樹脂(室町化学工業(株)製 Dowex HCR W−2)に通し、1N NaOHにより溶出した。溶出画分を活性炭(二村化学工業(株)製太閤活性炭 SG)に通し、15%エタノールによる溶出画分をRO膜(日東電工(株)製 NTR 729 HF)を用いて濃縮し、カラムクロマトグラフィーにて精製し、更に再結晶を行い、L−テアニン24.8gを製造した。
なお、以下における各試験および各組成物の製造にはL−テアニン(商品名:サンテアニン、太陽化学株式会社製)を用いた。
SD系の雄ラット5週齢のもの(体重220−270g)を購入し、一週間固型飼料(ラボMRストック)と飲水(水道水)で飼育した後、実験に供した。L−テアニンを水溶液にして、ゾンデにより体重kgあたり、0.05、0.1、0.5、1、5、10、100、及び500mgを投与した。その後、強制歩行器(KN−73 トレッドミル:株式会社フルヤ製)で毎分5mの速度で3時間強制歩行させた。3時間歩行後、常法に従い脳脊髄液および血液を採取した。対照群として、テアニンの代わりに蒸留水を飲ませたラット、および運動負荷をさせていないラットを用いた。また、各試験群には、一群あたり5匹のラットを用いた。
脳脊髄液および血液中のTGF−β濃度測定は、TGFβ1 EmaxTM ImmunoAssay System(Promega社製)を用いて行った。96穴ELISAプレート(MaxiSorp:Nunc社製)の各ウェルにAnti−TGF−β Coat mAB 10μlとCarbonate coating buffer 10mlを混合したもの100μlを添加し、プレートシーラーでプレートをシールし、4℃で一晩インキュベートした。コーティングした液を捨てた後、Block 1x buffer 270μlを添加し、37℃で35分間インキュベートし、TBSTで5回洗浄した。
図1に示すように、血中TGF−β1濃度は、コントロール群(蒸留水投与)に比べて、テアニン0.1mg/kg〜100mg/kg投与群において有意に抑制された。また、図2に示すように、脳脊髄液中TGF−β1濃度は、コントロール群(蒸留水投与)に比べて、テアニン0.5mg/kg〜100mg/kg投与群において有意に抑制された。
上記試験例によれば、テアニンの投与により、血中および脳脊髄液中TGF−β濃度の抑制効果があることが示された。
テアニン配合TGF−β抑制用組成物含有医薬品の1例として、次に示す原料を混合後打錠し、テアニン配合錠剤を製造した。
なお、キャンディー中のL−テアニンの含量を測定した結果、キャンディー1個(1.2g)について、89.6mg/gであった。
上記実施例3〜実施例6について、テアニンを配合しないものを製造して、食感及び風味を比較したところ、差異は認められなかった。
Claims (4)
- テアニンを有効成分とする形質転換増殖因子β抑制用組成物。
- 対象疾患が、慢性糸球体腎炎、腎臓間質性線維症、糖尿病性腎症、肝線維症、肝硬変、肺繊維症、ケロイド、強皮症、動脈硬化、後部心筋梗塞、心臓性線維症、血管形成後再狭窄、急性巨核芽球性白血病、成人T細胞白血病、慢性疲労症候群、一般的な疲労のうちの少なくとも一つであることを特徴とする請求項1に記載の組成物。
- 請求項1または2記載の組成物を含有する飲食品。
- 請求項1または2記載の組成物を含有する医薬品。
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| JP2004245916A JP5144000B2 (ja) | 2004-08-25 | 2004-08-25 | 形質転換増殖因子β抑制用組成物 |
| US11/209,126 US20060045905A1 (en) | 2004-08-25 | 2005-08-22 | Composition for repressing transformation growth factor beta |
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| JP5225277B2 (ja) * | 2007-07-24 | 2013-07-03 | 国立大学法人 琉球大学 | 自己抗体の産生に関連する疾患の予防又は治療のための組成物 |
| US9855370B2 (en) | 2008-01-08 | 2018-01-02 | Yale University | Compositions and methods for promoting patency of vascular grafts |
| WO2012167261A2 (en) | 2011-06-03 | 2012-12-06 | Yale University | Compositions and methods for treating and preventing neointimal stenosis |
| US10456418B2 (en) | 2015-10-05 | 2019-10-29 | Navinta, Llc | Preparation of pharmaceutical dosage forms containing iron (III) salts |
| CA3007631A1 (en) | 2015-12-11 | 2017-06-15 | Research Institute At Nationwide Children's Hospital | Optimized patient specific non-linear tissue engineered vascular grafts |
| KR102346511B1 (ko) * | 2019-02-27 | 2022-01-03 | 종근당건강 주식회사 | 타라곤(Tarragon, Little Dragon, Mugwort, Estragon) 추출물을 함유하는 근육질환 예방 또는 치료용 조성물 |
| KR102320221B1 (ko) * | 2020-01-21 | 2021-10-29 | 한국식품연구원 | 쥐오줌풀 추출물을 유효성분으로 포함하는 근육 질환 예방, 개선 또는 치료용 조성물 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2000159673A (ja) * | 1998-11-27 | 2000-06-13 | Taisho Pharmaceut Co Ltd | 形質転換増殖因子β阻害剤 |
| JP2001187736A (ja) * | 1999-10-20 | 2001-07-10 | Ito En Ltd | 滋養強壮剤及び滋養強壮飲食物 |
| JP2001316256A (ja) * | 2000-04-28 | 2001-11-13 | Taiyo Kagaku Co Ltd | 血流改善用組成物 |
| JP2003055213A (ja) * | 2001-08-17 | 2003-02-26 | Ito En Ltd | 遺伝子転写制御因子のdna結合能抑制剤 |
| JP2003267866A (ja) * | 2002-03-13 | 2003-09-25 | Japan Science & Technology Corp | 抗糸球体腎炎処方剤 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000159673A (ja) * | 1998-11-27 | 2000-06-13 | Taisho Pharmaceut Co Ltd | 形質転換増殖因子β阻害剤 |
| JP2001187736A (ja) * | 1999-10-20 | 2001-07-10 | Ito En Ltd | 滋養強壮剤及び滋養強壮飲食物 |
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| JP5144000B2 (ja) | 2013-02-13 |
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