JP5042820B2 - 生物活性表面を有する物品およびそれらの無溶媒調製法 - Google Patents
生物活性表面を有する物品およびそれらの無溶媒調製法 Download PDFInfo
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0076—Chemical modification of the substrate
- A61L33/0088—Chemical modification of the substrate by grafting of a monomer onto the substrate
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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- G01N33/54353—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals with ligand attached to the carrier via a chemical coupling agent
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Description
重合モノマーでガラス試料をコーティングするためのプラズマ処理プロセスは、直径12インチ(約30cm)で高さ18インチ(約46cm)の直立円筒形真空チャンバー内で行った。ガラス試料は、チャンバーの中央平面に位置する高周波を動力とする直径8インチ(約20cm)の電極上に置いた。約5立方センチメートルのAPTMSの入った直径1インチ(約2.5cm)で高さ2インチ(約5cm)の開放したバイアルを電極上に置いた。初めに、システムを、回転翼粗引ポンプの支援でターボ分子ポンプにより、約8ミリTorr(約0.001kPa)の圧力まで真空排気した。次いで、ポンピングラインのバルブを締め、気化モノマーの圧力を一定の85ミリTorr(約0.01kPa)まで上昇させた。次いで、電極を、22ワットの電力を送るためのマッチング回路と直列で、13.56MHzの高周波発電機により刺激した。このようにして発生させたプラズマを、60秒間操作し、ガラス基板の表面上でモノマー蒸気を被膜に重合させた。
実施例1に記載されているように、BD Labware96ウエルガラス底プレート(カタログ番号3537311)をAPTMSプラズマに暴露させた。続いて、多糖(ヒアルロン酸、Lifecore Biomedical)を含む生物活性表面を、水性EDC/NHSカルボジイミドカップリング化学反応を用い、プレートの半数のウエルのプラズマでコーティングされた表面に共有結合させた。MC3T3細胞(マウス、骨芽細胞)を、10%FBSを含有する200μLのαMEM培地中、ウエル当たり10,000個の細胞で96ウエルプレートのすべてのウエルに播種した。APTMSのみでコーティングされたプレートの区画は、顕著な細胞接着および48時間までの増殖を示した。APTMS表面と結合させたHAでコーティングされた半数のプレートは、同じ48時間以内に細胞が接着するのを許さなかった。したがって、接着依存性細胞は、接着できなかったため、本明細書に記載されている方法に従って調製される培養プレート表面上で増殖または広がることができなかった。したがって、この方法により調製される表面および物品は、非汚染性にされた。
グルコースセンサーは、コア径400μmの光ファイバーの一方の端で調製し、他方の端は、蛍光検出装置に連結した。ファイバーの磨き上げたセンシング末端を、実施例1におけるようにAPTMSでコーティングした。アルギネートをベースにしたヒドロゲルマトリックスを含む生物活性表面を、APTMS層に結合させた。アルギネートヒドロゲルマトリックスは、カルボジイミド化学反応を介し、アジピン酸ジヒドラジド(AAD)と共にカルボキシルを介してPronova(商標)UP LVGアルギネートを共有結合的に架橋することにより調製した。Pronova(商標)UP LVGは、その低い粘性および高いグルロン酸対マンヌロン酸比で選択した。2%アルギネート溶液は、アルギネート1グラムを0.1M MES緩衝液(pH 6.0)50mLに溶かし、AAD110mgおよびヒドロキシベンゾトリアゾール(HOBt)79mgを加えることにより調製した。溶液は、必要になるまで4℃にて保存することができる。デュアルシリンジ混合技法を用い、アルギネート溶液に、溶液10mL当たり1−エチル−3−(3−ジメチルアミノ−プロピル)カルボジイミド(EDC)145mgを加えた。アルギネート/AAD/HOBt/EDC混合物を、付いている30ゲージの針で1mLのシリンジ中に吸引した。針を準備し、次いで、アルギネートの小さな玉と一緒に、先端部を、APTMSでコーティングされた光ファイバー先端部に付けた。マトリックスは、約2〜5分間で架橋した。ファイバー先端部およびマトリックス集合を水和チャンバーに移し、2時間保存した。2時間の最後に、センシングチップを、過剰のpH 8.5エタノールアミンに15分間入れ、反応をクエンチした。
Claims (16)
- 生物活性表面を含む物品であって、
a)ガラス基板であって、前記ガラス基板は遊離反応基を含むヒドロキシルに富んだポリマー層をさらに含むガラス基板、
b)前記ヒドロキシルに富んだポリマー層上のアミノプロピルトリメトキシシラン(APTMS)層であって、前記APTMS層は無溶媒環境において前記ヒドロキシルに富んだポリマー層上に沈着された実質的に均一な厚さでありかつ実質的に無欠陥であるAPTMS層、および
c)前記APTMS層に共有結合している生物学的機能分子を含むことを特徴とする物品。 - 前記生物学的機能分子は、アルギネート、ヒアルロン酸、ポリエチレングリコール、メタクリル酸ヒドロキシエチル、ポリラクチド、ポリグリコール酸およびそれらのコポリマーからなる群から選択されることを特徴とする請求項1に記載の物品。
- 前記生物学的機能分子は、ヒアルロン酸であることを特徴とする請求項1に記載の物品。
- 前記生物学的機能分子は、前記生物活性表面上に三次元構造を付与することを特徴とする請求項1に記載の物品。
- 前記ヒドロキシルに富むポリマー層は、ポリメタクリル酸ヒドロキシエチル(polyHEMA)であることを特徴とする請求項1に記載の物品。
- 光ファイバーであることを特徴とする請求項1に記載の物品。
- 近位末端および遠位末端を有し、前記APTMS層は、前記ファイバー遠位末端の少なくとも一部の上に存在することを特徴とする請求項6に記載の光ファイバー。
- 前記生物学的機能分子は、光ファイバー遠位末端に共有結合しているポリマーマトリックスを含み、前記ポリマーマトリックスは、試料中の標的分析物を検出するためのセンシング素子を受け入れるように形状が決められていることを特徴とする請求項7に記載の光ファイバー。
- 前記ポリマーマトリックスは、ヒアルロン酸(HA)、アルギネート(AA)、ポリエチレングリコール(PEG)、メタクリル酸ヒドロキシエチル、ポリラクチド、ポリグリコール酸、メタクリレート、アクリレート、メタクリレート−メタクリル酸ヒドロキシエチル、アクリレート−メタクリル酸ヒドロキシエチル、およびアクリレート−メタクリレート−メタクリル酸ヒドロキシエチルからなる群から選択されることを特徴とする請求項8に記載の光ファイバー。
- 請求項8に記載の光ファイバーおよびポリマーマトリックス中に封入されるか、あるいはポリマーマトリックスに接続されるセンシング素子を含むことを特徴とするバイオセンサー。
- 前記センシング素子は、少なくとも1つの発光性標識されたペリプラズム結合タンパク質を含むことを特徴とする請求項10に記載のバイオセンサー。
- ガラスの組織培養容器であることを特徴とする請求項1に記載の物品。
- 請求項1に記載の物品を製造する方法であって、
a)前記ガラス基板に遊離反応基を含むヒドロキシルに富んだポリマー層をコーティング処理して、前記ガラス基板の表面上に遊離反応基を形成すること、
b)無溶媒環境において前記処理済みガラス基板上に前記APTMS層を沈着すること、および
c)前記APTMS沈着層上に生物学的機能分子を共有結合させて前記物品の生物活性表面を提供することを含むことを特徴とする方法。 - 無溶媒環境において前記処理済みガラス基板上にAPTMS層を沈着することは、気相沈着により行われることを特徴とする請求項13に記載の方法。
- 前記気相沈着は、化学気相沈着もしくは物理気相沈着または化学気相沈着と物理気相沈着の組合せであることを特徴とする請求項14に記載の方法。
- 前記気相沈着は、プラズマを含むことを特徴とする請求項14に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US57081604P | 2004-05-14 | 2004-05-14 | |
US60/570,816 | 2004-05-14 | ||
PCT/US2005/017019 WO2006085898A1 (en) | 2004-05-14 | 2005-05-16 | Articles having bioactive surfaces and solvent-free methods of preparation thereof |
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JP2008538079A JP2008538079A (ja) | 2008-10-09 |
JP5042820B2 true JP5042820B2 (ja) | 2012-10-03 |
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JP2007513451A Expired - Fee Related JP5042820B2 (ja) | 2004-05-14 | 2005-05-16 | 生物活性表面を有する物品およびそれらの無溶媒調製法 |
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US (1) | US7815922B2 (ja) |
EP (1) | EP1744795A1 (ja) |
JP (1) | JP5042820B2 (ja) |
WO (1) | WO2006085898A1 (ja) |
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US20050255327A1 (en) | 2005-11-17 |
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