JP2017525458A - オリゴマー化されたポリフェノール層を含む、物品のコーティング、および、生物学的方法の使用 - Google Patents
オリゴマー化されたポリフェノール層を含む、物品のコーティング、および、生物学的方法の使用 Download PDFInfo
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- JP2017525458A JP2017525458A JP2017506898A JP2017506898A JP2017525458A JP 2017525458 A JP2017525458 A JP 2017525458A JP 2017506898 A JP2017506898 A JP 2017506898A JP 2017506898 A JP2017506898 A JP 2017506898A JP 2017525458 A JP2017525458 A JP 2017525458A
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- polyphenol
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- polymer
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Abstract
Description
本非仮出願は、シリアルナンバーが62/035,173であり、2014年8月8日にファイルされ、タイトルが「ARTICLE COATINGS INCLUDING OLIGOMERIZED POLYPHENOL LAYER AND BIOLOGICAL METHODS OF USE」である仮出願が有する利益を請求する。当該仮出願は、その全体が、本非仮出願中に参考として援用される。
本発明は、医療用、診断用、および、細胞培養用の物品のためのコーティングに関する。
本発明の実施形態には、様々な物品(例えば、医療用、診断用、および、細胞培養用の物品)のためのコーティングが含まれる。本発明の実施形態には、また、コーティングされた物品を使用する方法が含まれる。
本発明は、以下の図面との関連において、より良く理解され得る。
本明細書における“ポリフェノール”は、2個〜約20個のフェノール単位(phenolic unit)を有する有機分子である。典型的なポリフェノールは、次の特性の1つ以上によって任意に特徴づけられ得る;つまり、(1)非重合体分子、(2)約200〜5000Daの範囲の分子量、(3)1つのフェノール単位あたり、1個〜3個のヒドロキシル基を有する、および、(4)1000Daあたり、5個〜8個の芳香環を有する。典型的なポリフェノールは、互いに結合している2個以上のフェノール単位を含む。典型的なポリフェノール単位は、レゾルシノール、ピロカテコール、ピロガロール、フロログルシノールおよびそれらの混合物から選択される。上記フェノール単位は、様々な化学基(例えば、エステル基、エーテル基、またはC−C基)を介して結合し得る。
まず、タンニン酸の繋ぎ目層を、ポリウレタン(PU)7F カテーテル(Solomon Scientific)の7cmの部分に塗布した。2mg/mLのタンニン酸(TA)溶液を調製するために、80mgのTAを、40mLの水性緩衝溶液中に溶解した。なお、当該水性緩衝溶液は、0.5M NaHCO3、および、0.5M NaCl(最終PH:8.3)を含むものであった。カテーテルの部分にタンニン酸溶液を加え、穏やかに反転させ、カテーテルの内腔から、付着しているあらゆる気泡を除去した。次いで、振とうさせること無く、50℃にて1時間、カテーテルをインキュベートした。インキュベーションの後、カテーテルの部分から除去し、内部直径(internal diameter)および外部直径(outer diameter)の両方を、水を用いて完全に洗浄し、空気乾燥を行った。
コーティングのタンパク質吸着特性を調べるために、ELISAの技術を用いて、コーティングされたカテーテル、および、コーティングされていないカテーテルに対するフィブリノーゲンの吸着を定量化した。ポリウレタンカテーテルを1cmの長さのサンプルに切り取り、12×75mmのガラスの試験管内に配置した(4サンプル/試験管)。ヒトの乏血小板血漿(George King Bio−Medical製のPPP)を、リン酸緩衝生理食塩水(PBS)を用いて、1:4に希釈した。2mLの希釈したPPPを、各試験管に加えた。サンプルを、室温にて2時間、オービタルシェーカー(orbital shaker)上で振とうしながら、インキュベートした。サンプルの血漿を吸引除去し、0.05%(v/v)Tween20、pH7.4を含むPBS洗浄溶液を用いて、サンプルを3回洗浄した。次いで、2mLの抗ヒトフィブリノーゲーンポリクローナル抗体−HRP(Rockland,Inc., 製品#200−103−240)を、PBS中で1:10,000に希釈されるように、各試験管に加えた。サンプルを、室温にて30分間、オービタルシェーカー上で振とうしながら、インキュベートした。抗体溶液を吸引除去し、PBSにTween20洗浄溶液を加えたものを用いて、サンプルを3回洗浄した。
表面修飾の血液親和性を決定するための有用な試験には、部分トロンボプラスチン時間(PTT(partial thromboplastin time))テストがある。当該PTTは、凝固における、固有(ファクターVIII、ファクターIX、ファクターXI、および、ファクターXII)の経路、および、共通(フィブリノーゲン、プロトロンビン、ファクターV、および、ファクターX)の経路に関するテストである。
Nunc maxisorb(最適なタンパク質の吸着に処理されたポリスチレン)、および、Greiner UV−Star(環状ポリオレフィン)の96ウェルのマイクロタイタープレートをタンニン酸によってコーティングし、次いで、典型的(model)な免疫アッセイによって試験した。
Claims (35)
- コーティングを備えた医療器具であって、
上記コーティングは、オリゴマー化されたポリフェノールを含む第1の被膜と、合成ポリマーまたは天然ポリマーを含む第2の被膜と、を含み、
上記合成ポリマーおよび天然ポリマーは、上記オリゴマー化されたポリフェノールに対して水素結合しており、
上記第1の被膜は、物品の表面と上記第2の被膜との間に配置されている、医療器具。 - 上記オリゴマー化されたポリフェノールは、500Da〜4000Daの分子量を有するポリフェノールを含んでいる、請求項1に記載の医療器具。
- 上記オリゴマー化されたポリフェノールは、12個以上のフェノール性ヒドロキシル基を有するポリフェノールを含んでいる、請求項1または2に記載の医療器具。
- 上記オリゴマー化されたポリフェノールは、没食子酸を含む組成物のエステル化によって得られるポリフェノールを含んでいる、請求項1〜3の何れか1項に記載の医療器具。
- 上記オリゴマー化されたポリフェノールは、タンニン酸を含んでいる、請求項1〜4の何れか1項に記載の医療器具。
- 上記第1の被膜および上記第2の被膜層は、厚さの合計が、250nm以下または100nm以下である、請求項1〜5の何れか1項に記載の医療器具。
- 上記合成ポリマーおよび天然ポリマーは、複数のヒドロキシル基を有している、請求項1〜6の何れか1項に記載の医療器具。
- 上記合成ポリマーは、ビニルピロリドン含有ポリマーである、請求項1〜7の何れか1項に記載の医療器具。
- 上記ビニルピロリドン含有ポリマーは、ビニルピロリドンホモポリマーまたはビニルピロリドン含有コポリマーである、請求項8に記載の医療器具。
- 更に、酸性基含有ポリマーを含む第3の被膜を含み、
上記第3の被膜は、上記第2の被膜と直接接触している、請求項1〜9の何れか1項に記載の医療器具。 - 上記酸性基含有ポリマーは、アクリル酸含有ポリマーである、請求項10に記載の医療器具。
- 上記アクリル酸含有ポリマーは、150kDa以上の平均分子量を有する、請求項11に記載の医療器具。
- 上記第2の被膜、上記第3の被膜、または、これらの両方が、更に、少なくとも1つの光反応性基を含んでいる、請求項10〜12の何れか1項に記載の医療器具。
- 上記光反応性基は、上記第2の被膜の合成ポリマー若しくは天然ポリマー、上記第3の被膜の酸性基含有ポリマー、または、これらの両方に付加しているものである、請求項13に記載の医療器具。
- 架橋剤中に存在する2つ以上の光反応性基を含む、請求項13または14に記載の医療器具。
- 上記オリゴマー化されたポリフェノールは、ポリフェノールを架橋する無機金属イオンを含む、請求項1〜15の何れか1項に記載の医療器具。
- 上記コーティングは、上記器具の内面上に形成されている、請求項1〜16の何れか1項に記載の医療器具。
- カテーテルを備えた、請求項1〜17の何れか1項に記載の医療器具。
- ポリフェノールを含む第1の被膜組成物を医療器具の表面に塗布して、オリゴマー化されたポリフェノールを含む第1の膜を形成する工程と、
上記第1の膜上に第2の被膜組成物を塗布する工程であって、上記第2の被膜組成物は、合成ポリマーまたは天然ポリマーを含み、当該合成ポリマーおよび天然ポリマーは、上記オリゴマー化されたポリフェノールに対して水素結合する、工程と、を含む、医療器具をコーティングする方法。 - 請求項1〜18の何れか1項に記載のコーティングを備えた医療器具を形成する、請求項20に記載の方法。
- オリゴマー化されたポリフェノールを含む、止血用のコーティングを備え、
上記オリゴマー化されたポリフェノールは、体液と接触するように構成されている、医療器具。 - 血管インプラントおよび血管移植、創傷被覆材および創傷処置器具、止血バリア、閉鎖材料、メッシュおよびヘルニアプラグ、眼帯、および、子宮出血パッチからなる群より選択される、請求項21に記載の医療器具。
- 請求項21または22に記載の医療器具を、体内の標的部位内または標的部位上に配置する工程を含み、
上記コーティングは、体液と接触して、上記標的部位にて凝固を促進する、体の中または体の上の標的部位で凝固を促進する方法。 - 上記コーティングは、フィブリノーゲンの吸収を促進する、請求項23に記載の方法。
- in vitroの診断アッセイまたは細胞培養に用いられるように構成された物品であって、
上記物品は、オリゴマー化されたポリフェノールを含むコーティングを備えている、物品。 - ELISAプレート、マイクロ流体装置、または、診断スライドである、請求項25に記載の物品。
- 上記オリゴマー化されたポリフェノールを含むコーティングは、合成ポリマーまたは天然ポリマーによって不動態化されており、
上記合成ポリマーおよび天然ポリマーは、上記オリゴマー化されたポリフェノールに対して水素結合している、請求項25または26に記載の物品。 - in vitroの診断アッセイに用いるための請求項25〜27の何れか1項に記載の物品を備えている、診断キット。
- in vitroの診断アッセイまたは細胞培養にて、物品の表面への生体高分子の吸着を促進する方法であって、
オリゴマー化されたポリフェノールを含むコーティングを備えた物品と、生体高分子を含む組成物と、を接触させる工程を含み、
上記コーティングは、水素結合を介した上記生体高分子の上記オリゴマー化されたポリフェノールへの吸着を促進する、方法。 - 上記生体高分子は、ペプチド、タンパク質、核酸、または多糖である、請求項29に記載の方法。
- 上記タンパク質は、抗体若しくは抗体の断片、または、ペプチド若しくはタンパク質である検体である、請求項30に記載の方法。
- 上記方法は、ELISAである、請求項31に記載の方法。
- コーティングを有する内面を備えた医療器具であって、
上記コーティングは、オリゴマー化されたポリフェノールを含む、医療器具。 - 上記コーティングは、カテーテルの内部直径上に形成されている、請求項33に記載の医療器具。
- 請求項33または34に記載の医療器具を患者に移植する工程を含む、医療器具の表面上にバクテリアが付着することを低減または防止する方法。
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JP2021520957A (ja) * | 2018-05-15 | 2021-08-26 | ボストン サイエンティフィック サイムド,インコーポレイテッドBoston Scientific Scimed,Inc. | 帯電したポリマーコーティングを備えた閉塞性医療装置 |
JP7241095B2 (ja) | 2018-05-15 | 2023-03-16 | ボストン サイエンティフィック サイムド,インコーポレイテッド | 帯電したポリマーコーティングを備えた閉塞性医療装置 |
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RU2017107413A3 (ja) | 2018-09-11 |
BR112017002527B1 (pt) | 2021-03-23 |
US11938250B2 (en) | 2024-03-26 |
RU2017107413A (ru) | 2018-09-11 |
CA2956721C (en) | 2023-09-12 |
CN106794283A (zh) | 2017-05-31 |
CN106794283B (zh) | 2021-03-02 |
US20190275209A1 (en) | 2019-09-12 |
JP6650436B2 (ja) | 2020-02-19 |
MX2017001626A (es) | 2017-05-09 |
RU2711535C2 (ru) | 2020-01-17 |
CA2956721A1 (en) | 2016-02-11 |
US20170224876A1 (en) | 2017-08-10 |
BR112017002527A2 (pt) | 2017-12-05 |
EP3177332B1 (en) | 2021-06-30 |
WO2016022796A1 (en) | 2016-02-11 |
EP3177332A1 (en) | 2017-06-14 |
US10201637B2 (en) | 2019-02-12 |
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