JP2016005773A - 新規なヘパリン体とその利用法 - Google Patents
新規なヘパリン体とその利用法 Download PDFInfo
- Publication number
- JP2016005773A JP2016005773A JP2015183860A JP2015183860A JP2016005773A JP 2016005773 A JP2016005773 A JP 2016005773A JP 2015183860 A JP2015183860 A JP 2015183860A JP 2015183860 A JP2015183860 A JP 2015183860A JP 2016005773 A JP2016005773 A JP 2016005773A
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- Prior art keywords
- heparin
- substrate
- medical
- substrate according
- heparinase
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Abstract
【解決手段】本発明には、少なくとも1個のヘパリン分子を通じて基板の表面に結合したヘパリン体を備えていて、結合したそのヘパリン体がヘパリナーゼ感受性である医療用基板も含まれる。
【選択図】図1
Description
この実施例では、ヘパリンと、コアとしての硫酸コリスチンとを含むヘパリン体の構成を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
この実施例では、ヘパリンと、コアとしての硫酸ネオマイシンとを含むヘパリン体の構成を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
この実施例では、ヘパリンと、コアとしての硫酸カプレオマイシンとを含むヘパリン体の構成を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
この実施例では、ヘパリンと、コアとしてのポリ-L-リシンとを含むヘパリン体の構成を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
この実施例では、ヘパリンと、コアとしてのポリエチレンイミン(PEI)とを含むヘパリン体の構成を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
この実施例では、ヘパリンと、コアとしてのエチレンジアミン(EDA)とを含むヘパリン体の構成を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
実施例1〜6の自由端アルデヒドを含むヘパリン体をePTFE基板の表面に固定化し、ATIII活性を試験した。
実施例2、3、4、6で製造した自由端アルデヒド含有ヘパリン体を分析して絶対分子量を調べた。
この実施例では、基板表面へのヘパリンまたはヘパリン体の付着法を識別する検出法を示す。この実施例では特に、自由端アルデヒドを含む単点付着とカルボジイミド共役を含む多点付着を利用したePTFE基板の表面への固定化を通じたヘパリンとヘパリン体の付着を見る。
この実施例では、殺菌後の基板表面へのヘパリン体の付着法を識別する検出法示す。この実施例では特に、自由端アルデヒドを含む単点付着を利用してePTFE基板の表面に固定化させることを通じてヘパリン体を付着させた後に殺菌してホウ酸で洗浄する場合を見る。
この実施例では、ヘパリナーゼ-1で解重合したヘパリン体を強陰イオン交換高性能液体クロマトグラフィ(SAX-HPLC)でオリゴ糖マッピングすることを利用してヘパリン体の組成を明らかにする検出法を示す。
この実施例では、ヘパリナーゼ-1で解重合したヘパリン体を強陰イオン交換高性能液体クロマトグラフィ(SAX-HPLC)でオリゴ糖マッピングすることを利用して、表面に固定化されたヘパリン体の組成を明らかにする検出法を示す。
この実施例では、ヘパリンと、ポリ-L-リシンを含むコアとを含むヘパリン体の構造を記載する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいない。このヘパリン体は、イオン結合を通じて基板の表面に付着させるのに使用できる。
実施例13のヘパリン体をイオン結合を通じてePTFE基板の表面に固定化した。
この実施例では、ヘパリンとヘパリン体を表面に固定化するための共役法をあきらかにするための検出法を示す。この実施例では特に、ヘパリナーゼ-1で解重合した後に、固定化されたヘパリンまたはヘパリン体の表面にある表面結合不飽和ヘパリン断片または“節”の検出を見る。ヘパリナーゼ-1によるヘパリンの解重合には、ヘパリンの非還元性末端ウロン酸が酵素によって開裂し、さまざまな検出分子(例えばチオール-テルビウム蛍光分子)と反応させることができる4,5-不飽和誘導体になることが含まれる。イオン結合したヘパリンの負の対照(実施例14)が含まれる。
この実施例では、ヘパリンとアンチトロンビンIII(ATIII)の結合が多い、ヘパリンと、アミン含有フルオロポリマーを含むコアとを含むヘパリン体に関する本発明の一実施態様の構成と利用法を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
この実施例では、ヘパリンとアンチトロンビンIIIの結合が多い、ヘパリンと、アミン含有フルオロポリマーを含むコアとを含むヘパリン体に関する本発明の一実施態様の構成と利用法を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる、ヘパリン成分の長さに沿ったアルデヒドを含んでいる。
実施例7に記載した方法に従い、ヘパリンと、アミン含有フルオロポリマーを含むコアとを含む実施例16と17のヘパリン体をePTFE/PEI基板の表面に固定化したが、サンプルをEtOに曝露しなかった点が異なっている。実施例7に記載した方法に従ってATIII結合活性を測定した。
この実施例では、ヘパリンとアンチトロンビンIIIの結合が多い、ヘパリンと、アミン含有フルオロポリマーを含むコアとを含むヘパリン体に関する本発明の一実施態様の構成と利用法を説明する。このヘパリン体は、基板の表面に付着させるのに使用できる自由端アルデヒドを含んでいる。
Claims (21)
- 少なくとも1個のヘパリン分子を通じて基板の表面に結合したヘパリン体を含む医療用基板であって、該ヘパリン体が少なくとも1個のヘパリン分子と少なくとも1個のコア分子とを含み、該結合したヘパリン体がヘパリナーゼ感受性であり、かつ、該ヘパリン分子が該基板に対し、端点付着、ループ付着、端点アルデヒド付着またはアルデヒド付着により、該ヘパリンの長さに沿って付着している、医療用基板。
- 前記基板が、ポリエチレン、ポリウレタン、シリコーン、ポリアミド含有ポリマー、ポリプロピレン、ポリテトラフルオロエチレン、延伸ポリテトラフルオロエチレンおよび生体適合性金属からなる群から選ばれる、請求項1に記載の医療用基板。
- 前記基板が延伸ポリテトラフルオロエチレンである、請求項2に記載の医療用基板。
- 前記生体適合性金属がニチノールである、請求項2に記載の医療用基板。
- 前記基板が医療装置の一部品である、請求項1に記載の医療用基板。
- 前記医療装置が、グラフト、血管グラフト、ステント、ステント-グラフト、分岐グラフト、分岐ステント、分岐ステント-グラフト、パッチ、栓子、薬剤送達装置、カテーテル、心臓用リード線、バルーンおよび留置フィルタからなる群から選ばれる、請求項5に記載の医療用基板。
- 前記ステントを心臓、末梢、神経の用途に使用できる、請求項6に記載の医療用基板。
- 前記ステント-グラフトを心臓、末梢、神経の用途に使用できる、請求項6に記載の医療用基板。
- 前記コア分子が、環形、直線形、分岐形、樹枝形、Y字形、T字形または星形のいずれかである、請求項1に記載の医療用基板。
- 前記コア分子が、タンパク質、炭化水素、アミノグリコシド、多糖およびポリマーからなる群から選択される、請求項1に記載の医療用基板。
- 前記タンパク質が、アルブミン、コリスチンおよびポリリシンからなる群から選択される、請求項10に記載の医療用基板。
- 前記多糖が、シクロデキストリン、セルロースおよびキトサンからなる群から選択される、請求項10に記載の医療用基板。
- 前記ポリマーが、ポリエチレングリコール(PEG)およびテトラフルオロエチレンのコポリマーからなる群から選択される、請求項10に記載の医療用基板。
- 前記ヘパリンがウシ又はブタに由来する、請求項1に記載の医療用基板。
- ヘパリナーゼ処理の後、ヘパリンまたはその断片が前記基板上で検出されない、請求項1に記載の医療用基板。
- ヘパリナーゼ処理の後、ヘパリンまたはその断片が前記基板上で、ヘパリナーゼ処理の前よりも有意に低いレベルで検出される、請求項1に記載の医療用基板。
- 前記ヘパリンまたはその断片が、ヘパリンまたはその断片に結合する標識によって検出される、請求項15に記載の医療用基板。
- 前記ヘパリンまたはその断片に結合する前記標識が、染料、ポリクローナル抗体およびタンパク質からなる群から選ばれる、請求項17に記載の医療用基板。
- 前記染料がトルイジンブルーである、請求項18に記載の医療用基板。
- ヘパリナーゼ処理の後、わずかな量のトルイジンブルーが残留ヘパリンまたはその断片に結合するが、前記基板上では目視によって検出されない、請求項1に記載の医療用基板。
- ヘパリナーゼ処理の後、わずかな量のトルイジンブルーが残留ヘパリンまたはその断片に結合し、検出器の読みが、バックグラウンドのレベルであるか、またはヘパリン体なしの基板と比較してバックグラウンドと有意差がない、請求項1に記載の医療用基板。
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JP6290840B2 (ja) | 2018-03-07 |
JP2013505070A (ja) | 2013-02-14 |
CN102695530B (zh) | 2018-11-30 |
ES2668220T3 (es) | 2018-05-17 |
EP2477668B1 (en) | 2018-02-07 |
CA2774494A1 (en) | 2011-03-24 |
WO2011035001A8 (en) | 2012-04-19 |
RU2012115097A (ru) | 2013-10-27 |
AU2010295601B2 (en) | 2014-02-13 |
US8591932B2 (en) | 2013-11-26 |
CN102695530A (zh) | 2012-09-26 |
US20110064781A1 (en) | 2011-03-17 |
CA2838352A1 (en) | 2011-03-24 |
EP2477668A2 (en) | 2012-07-25 |
JP2017192801A (ja) | 2017-10-26 |
JP6538767B2 (ja) | 2019-07-03 |
AU2010295601A1 (en) | 2012-05-10 |
CA2838352C (en) | 2018-04-24 |
WO2011035001A3 (en) | 2011-08-18 |
JP5814242B2 (ja) | 2015-11-17 |
BR112012006144A2 (pt) | 2016-06-28 |
US20140128544A1 (en) | 2014-05-08 |
US20110065085A1 (en) | 2011-03-17 |
WO2011035001A2 (en) | 2011-03-24 |
RU2576803C2 (ru) | 2016-03-10 |
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