JP6665162B2 - カスタマイズ可能な医療デバイスを製造するための方法およびその方法によって得られたデバイス - Google Patents
カスタマイズ可能な医療デバイスを製造するための方法およびその方法によって得られたデバイス Download PDFInfo
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- JP6665162B2 JP6665162B2 JP2017508082A JP2017508082A JP6665162B2 JP 6665162 B2 JP6665162 B2 JP 6665162B2 JP 2017508082 A JP2017508082 A JP 2017508082A JP 2017508082 A JP2017508082 A JP 2017508082A JP 6665162 B2 JP6665162 B2 JP 6665162B2
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Description
支持体を金属性の層でコーティングするための方法
第1の態様において、本発明は、支持体を金属でコーティングするための方法(以下、本発明の第1の方法)であって、
(i)支持体の少なくとも第1の表面を、活性化されたカルボキシル基を含有する反応性モノマーと、前記モノマーの重合による前記支持体の前記表面上での前記活性化されたカルボキシル基を含有するポリマーコートの形成に十分な条件下で接触させる工程、
(ii)工程(i)で得られた前記支持体を、前記活性化されたカルボキシル基と反応性の基を含んでなる還元性炭水化物と、前記炭水化物中の前記反応性の基と前記支持体の前記表面上の前記活性化されたカルボキシル基との間の共有結合の形成に十分な条件下で接触させ、それによって、還元性炭水化物で修飾された表面を得る工程、および
(iii)工程(ii)で得られた表面を、前記金属由来の金属性イオンの塩と、前記還元性炭水化物による前記金属性イオンの還元および前記表面上への前記金属性イオンの堆積に十分な条件下で接触させ、それによって、前記金属性イオンでコーティングされた表面を得る工程
を含む、方法に関する。
R−CO−L
(式中、Rは、カチオン重合、アニオン重合またはフリーラジカル重合が可能な基であり、Lは脱離基である)
を有する分子を意味する。
Ag2O+4NH4OH→2[Ag(NH3)2]++2OH−+3H2O
[Ag(NH3)2]++e−→Ag+2NH3
第1の方法の第1の工程はまた、支持体の表面を、治療上活性である化合物を含有する粒子で修飾するために使用することができる。一度、本発明の第1の方法の第1の工程が適用されると、重合した反応性モノマーによって覆われた支持体の表面がもたらされ、前記支持体は、反応性基で修飾された、前記治療上活性である化合物を含有する粒子によってさらに修飾することができる。
(i)支持体の少なくとも第1の表面を、活性化されたカルボキシル基を含有する反応性モノマーと、前記モノマーの重合による前記支持体の前記表面上での前記活性化されたカルボキシル基を含有するポリマーコートの形成に十分な条件下で接触させる工程、および
(ii)工程(i)で得られた支持体を、前記活性化されたカルボキシル基と反応性の基で修飾された粒子と接触させる工程であって、ここで、前記粒子は、ナノ粒子およびマイクロ粒子から選択され、前記粒子は、少なくとも治療上活性である化合物を含有し、かつ前記接触は、前記ナノ粒子中の前記反応性基と前記支持体の前記表面上の前記活性化されたカルボキシル基との間の共有結合の形成に十分な条件下で行われ、それによって、ナノ粒子による前記第2の表面の修飾がもたらされる工程
を含む、方法に関する。
別の態様では、本発明は、本発明の第1の方法によって得ることができる支持体(以下、本発明の第1の支持体)に関する。
(i)ポリマー材料の内部コートであって、該ポリマーが、該層中のカルボキシル基と該炭水化物中のカルボキシル基と反応性の基との間で形成されたポリマー層につながれた酸化単糖類で修飾されている内部コート、および
(ii)前記金属のイオンの還元によって生成された金属の外部コート。
アルゴン5.0および酸素5.0は、Abello Linde S.A.(スペイン)から購入した。PFMは、Apollo ScientificLTD(UK)から購入した。D−(+)−グルコサミン塩酸塩、デシルアミンおよび硝酸銀は、Sigma Aldrichから購入した。
この研究に使用した支持体はSiウエハーおよびポリジメチルシロキサン(PDMS)のサンプルであった。シルガード(Sylgard)(登録商標)184キット(Dowcorning, USA)を使用して、PDMSプレートを作製した。そのキット(10:1)を塗料アプリケーターにより薄く広げて、厚さ500μmのプレートを得た。これらのプレートを70℃で一晩インキュベートした。PDMSフィルムを21mmおよび10mmの円形に切断した。PDMSの高疎水性および帯電から、サンプルは正確な洗浄処理が必要であることを示すことが重要である。PDMSプレートをドデシル硫酸ナトリウム(Sodium Dodecyl Sulphate)(SDS、Sigma Aldrich)5%で洗浄し、milliQ水で洗い流し、ヘルマネックス(Hellmanex)(登録商標)(ヘルマ(Helma)(登録商標)Analytics、ドイツ)溶液2%で洗浄し、再びmilliQ水で、最後にエタノール(Scharlab、スペイン)で洗い流した。SiウエハーをPDMSプレートと同じプロトコールで洗浄した。次いで、サンプルを窒素気流中で乾燥させ、ヌンクラボテック(Nunc LabTek)(商標)製のペトリ皿で保存した。
この研究で行う表面修飾は、ステンレス鋼垂直型プラズマ反応器を使用して実施した。この反応器はステンレス鋼チャンバー(直径:25.5cm、長さ:41.6cm)垂直型プレート反応器)からなる。接地電極は反応器チャンバーであり、RF(無線周波数(Radio Frequency))電極は、重合のためのサンプルを保持するために使用されるアルミニウムプレートである。加えて、RF電極は、マッチングボックスを介してRFパルス発生器(13.56MHz)に接続される。ガスおよびモノマーは標準的なマニホールドを介して供給され、ガスフラックスはニードル弁のツリーで調整される。システム圧力は、反応器の中央に配置された冷陰極/マイクロピラニ真空トランスデューサー(MKS 972 DualMag、USA)と接続された真空計コントローラー(MKS PDR900、USA)を使用してモニタリングする。システムは、窒素冷却トラップと、未反応モノマーがポンプ(Trivac D 16BCS/PFPE Leybold、ドイツ)に到達するのを回避するために接続された活性炭で満たされた化学トラップを有する。総ての実験に対する典型的な基準圧力は6・10−4ミリバールであり、モノマー蒸気(PFM)は一定圧力で0.02〜0.04ミリバールに導入された。
支持体を反応器の中央のアルミニウムプレート上に置いた。支持体を導入する前に、チャンバーを連続波O2/Ar(1:1)プラズマ中、電力150Wでおよそ1時間清浄化した。連続無線周波数電力を15Wで固定し、パルスプラズマ重合(デューティーサイクル 10/20)を3〜5分間実施した。次いで、プラズマ放電を止め、PFM蒸気流をさらに3分間一定に保った。重合プロセス後、サンプル(pPFM)を反応チャンバーから注意深く取り出し、アルゴン雰囲気下でさらに使用するまで保存した。
修飾された表面を、水接触角(DSA100、KrUss; WCA)、飛行時間(ToF−SIMS)および高電圧での超高分解SEM−UHRSEM(NovaNanoSEM 230、FEI)によって特性評価した。WCAおよびAFMによる表面修飾を分析するために、修飾PDMSサンプルおよびSiウエハーの両方を重合後に直接分析した。TOF−SIMS分析は、5×10−9ミリバールの圧力で操作するTOF−SIMS IV(ION−TOF、Munster、ドイツ)を使用して行った。サンプルには、25keVのエネルギーでパルスビスマス液体金属イオン源(Bi3++)を用いて衝撃を与えた。銃は、静的SIMS条件で一般的に受け入れられている1×1013イオン/cm2の閾値レベルをはるかに下回る、5×1011イオン/cm2より低い線量のために20nsのパルス幅、0.3pAのパルスイオン電流を用いて操作した。二次イオンは、反射飛行時間分析器、マルチチャネルプレート(MCP)、および時間・デジタル変換器(TDC)を用いて検出した。測定は、TDC時間分解能200psおよび100usサイクル時間で典型的な取得時間10sを用いて行った。電荷中和は、低エネルギー(20eV)電子銃(electron flood gun)を用いて達成した。二次イオンスペクトルは、サンプルの表面内のランダムにラスター化した(randomly rastered)表面積100μm×100μmから取得した。二次イオンは、2kVの電圧で抽出し、検出器に当たる直前に10keVの運動エネルギーに後加速する。質量スペクトルの取得はION−TOF Ion Specソフトウェア(バージョン4.1)内で行った。
抗微生物コーティングを達成するために、トレンス法を用いて銀を還元糖により還元した。この方法は、銀イオンとアンモニアとの錯体形成と、それに続く加熱浴での還元糖を用いた還元にある。固定された糖を使用することによって、ジアミン銀(I)イオンは金属性の銀に還元され、表面コーティングが生じる。グルコサミン溶液は、グルコサミン塩酸塩をmilliQ水に1Mに溶解することによって調製した。次いで、pHを濃水酸化ナトリウムで7.4に調整した。グルコサミンと修飾された表面との間の反応は、修飾されたサンプルをグルコサミン溶液中で6時間インキュベートすることにより行った。トレンス試薬は、酸化銀の沈殿を観察して、25μlのアンモニア15%を1mlの硝酸銀0.1Mに加えることにより調製した。次いで、アンモニアによる銀の錯体形成による沈殿物の完全溶解を観察して、さらに25μlのアンモニア15%を加えた。付着したグルコサミンを含む修飾されたサンプルを4mlのmilliQ水が入ったバイアルに導入した。その後、1mlのトレンス試薬を加え、水浴で90℃で所望の反応時間60分間加熱した。ICP−OES(Optima 2100 DV、Perkin Elmer)を使用して銀を定量した。
ナノ粒子の固定は、ナノ粒子20mg/mlの懸濁液を用いて行った。懸濁液のpHは、濃水酸化ナトリウムで7.4に調製した。ナノ粒子の固定反応は、PFM修飾PDMSサンプルをナノ粒子懸濁液中で6時間インキュベートして行った。インキュベーションプロセス後に、サンプルをmilliQ水で徹底的に洗浄し、さらに使用するために圧縮空気で乾燥させた。
コーティングしたサンプルのAgイオン放出をICP−OESで測定した。異なるコーティングサンプルをTSB 5ml中およびmilliQ 5ml中に37℃で浸漬した。所望の時間経過後、各溶液4mlを分析のために抽出し、新しい溶液4mlと交換した。溶液を補充し、20日間毎日分析した。
パクリタキセルを担持した固定ナノ粒子を有する乾燥PDMSサンプルをアセトニトリルに溶解し、取り込まれた薬物の量を超高速液体クロマトグラフィー(Ultra Performance Liquid Chromatography)(UPLC)(Waters ACQUITY UPLC H−Class)を用いて検出した。逆相BEH C18カラム(1.7μm 2.1×50mm)を使用した。移動相は、移動相A(0.1%の酢酸を含有する水)および移動相B(0.1%の酢酸を含有するメタノール)の混合物(65:35v/v)で構成し、流速0.6ml/分で送達した。1.0μlアリコートをde UPLCシステムに注入し、全分析実行時間を3分とした。パクリタキセルと、内部標準(internal standard)(I.S.)としてのドセタキセルを、UV検出(λ=227nm、Waters TUV検出器)によって定量した。標準薬物溶液(パクリタキセル)およびI.S.の較正曲線を使用して、較正液を得、この較正曲線は、0.1〜2.5μg/mlのパクリタキセルの範囲で線形であり(6μg/mlのドセタキセルを含む)、相関係数はR2=0.995であった。薬物固定は式1を用いて計算した。
細菌培養は、バルセロナのHospital Bellvitgeで市販の緑膿菌(PA01)株および緑膿菌(282939)および黄色ブドウ球菌(329531)の臨床株を用いて実施した。細菌をTSB(トリプチックソイブロス(Tryptic Soy Broth))培地に播種して108cfu/ml 10mlを得、37℃で一晩撹拌した。インキュベーション後、希釈により107cfu/mlおよび106cfu/mlの細菌懸濁液20mlを調製した。PDMSサンプル(銀修飾および非修飾)を滅菌24ウェルプレート上に置き、各細菌懸濁液1mlを加えた。サンプルを含むプレートを、撹拌を行わずに37℃で24時間インキュベートした。インキュベーション時間経過後、各ウェルの上清を吸引し、サンプルをmilliQ水で7回洗浄した。続いて、サンプルを滅菌24ウェルプレートに入れ、各ウェルにライブ&デッド(Live&Dead)(登録商標)(Invitrogen)溶液を加えた(0.9%NaCl 2ml+溶液A 3μl+溶液B 3μl)。24ウェルプレートを光から保護し、15分間インキュベートした。インキュベーション時間経過後、サンプルをmilliQ水で洗浄し、それらの蛍光を共焦点顕微鏡で観察し;二重標識した切片の画像を、488nmアルゴンレーザー、543nmおよび633nm He/Neレーザー(Centres Cientifics i Tecnologics, Universitat de Barcelona、バルセロナ、スペイン)を備えたLeica TCS−SLフィルターフリースペクトル分光型共焦点レーザー走査顕微鏡(Leica Microsystems、マンハイム、ドイツ)を使用し、63×油浸対物レンズ(開口数1.4)、画像解像度1024×1024ピクセルを用いて取得した。
薬物を担持したナノ粒子の細胞毒性を評価するために、ヒト肺正常繊維芽細胞、妊娠6週(ATCC、CCL−186)は、10%FBS、5%ペニシリン/ストレプトマイシンおよびアムホテリシン(2.5μg/ml)を補給したEMEM(Gibco、Life Technologies)中で増殖させ、狭窄性繊維芽細胞(外科生検によって摘出したサンプル)は、10%FBS、5%ペニシリン/ストレプトマイシンおよびアムホテリシン(2.5μg/ml)を補給したDMEM(Gibco、Life Technologies)中で増殖させ、それらを使用した。細胞を96−ウェルプレートに細胞密度1000細胞/ウェルでプレーティングした。24時間後に、培地を吸引し、様々なパクリタキセル濃度(10nM、14nMおよび20nM)の薬物を含まないナノ粒子、1%および3%理論的薬物担持ナノ粒子の培地で置換した。同じ濃度範囲(10〜20nM)の非封入パクリタキセルを含む細胞である1つのカラムを陽性対照として使用し;ナノ粒子を含まず、パクリタキセルを含まない細胞である1つのカラムを対照として使用し;細胞を含まない別のカラムをブランクとして使用した。1日、4日、8日および12日後に、細胞生存率を、製造業者の説明書に従ってMTT(Quick Cell Proliferation Assay Kit II、JM−K302−500、MBL International Corporation、USA)によって評価した。簡潔には、細胞をPBSで洗浄し、MTT試薬および完全培地の溶液とともに37℃でインキュベートした。細胞生存率を表す吸収をマイクロプレートリーダー(Multiskan Ex、Thermo Scientific)によって450nmで測定した。細胞生存率は対照細胞と比較した生存細胞のパーセンテージとして表した。
ToF−SIMS
図1では、PDMS上へのpPFMコーティングの正および負の質量フラグメント、およびその後のグルコサミンとの反応と、最後にグルコサミンによる還元された銀を観察することができる。非修飾PDMSサンプルは、シリコン質量フラグメント、m/z=28、および追加のPDMS典型的ピーク−SiCH3 +、CH3SiO−、SiO2 −、SiC3H9 +、CH3SiO2 −およびSi2OC5H15 +(m/z=43、59、60、73、75および147)を示す。(Dietrich, R., Grobe, J., Meyer, K., Hagenhoff, B., & Benninghoven, A. Fresenius’ Journal of Analytical Chemistry 1994, 349(1-3), 221-222; Gardella, J. a., & Hercules, D. M. , Fresenius’ Zeitschrift Fur Analytische Chemie 1981, 308(3), 297-303; Karen, A., Man, N., Shibamori, T., & Takahashi, K., Applied Surface Science 2003, 203-204, 541-546)。PFM修飾サンプルは、典型的なメタクリレート低質量フラグメント−C2H3 +およびC2H5 +(m/z=27および29)を示す、図1A。PDMSシグナルおよびPFMシグナルが正のスペクトルに干渉するため;このタイプのサンプル(PDMS系)では、負のスペクトルは、負のイオンスペクトルにおけるフッ素化環を解明するために、より興味深いものであり得る、図1B。負のイオンスペクトルは、フッ素化環に関連したフッ素化フラグメント−F−およびF2H−(m/z=19および49)を示す。
銀放出
周知の通り、銀の抗菌活性は、金属性元素に起因するものではなく、銀イオン(Ag+)に起因するものである。しかしながら、その活性機構は現在論争中であり;銀イオンとシステインの錯体形成能力、DNAとの相互作用、細胞破壊または電子輸送の存在と関連しているようである。この点で、銀イオン放出の研究を、銀コーティングサンプルをTSBおよびmilliQ水中でインキュベーションを行うことによって実施する。
細菌培養
修飾サンプルの抗菌活性を試験するために、PDMSサンプルを、グラム陽性およびグラム陰性の代表としてそれぞれ黄色ブドウ球菌および緑膿菌を用いてインキュベートする。細菌増殖は、PA01菌株では、非修飾サンプルでも顕著に観察することができ、バイオフィルム構造を観察することができる。しかしながら、修飾サンプルでは、銀イオンの抗菌効果を観察することができる。図3Aでは、総ての修飾サンプルが、総ての細菌が死滅したことを示す細菌生存率の減少を示すことを観察することができる。これらの驚異的な抗菌活性は、培地上に可溶化された銀イオンと、下方のバイオフィルム構造と相互作用し、細菌の死滅を引き起こすことができる細菌の下の銀コートにも直接関係している(Stevens, K. N. J., et al., Biomaterials 2009, 30(22), 3682-90)。加えて、銀イオンの高い抗菌作用の結果としておよび銀コーティングのナノ構造によって引き起こされる疎水性表面から、表面上への余分な細菌接着は観察することができない。さらに、異なる菌株とのインキュベーション後、上清を再び集め、銀イオンの活性を観察するために再びインキュベートした。図3Bでは、両方の細菌株の生存率の減少、グラム陰性およびグラム陽性それぞれについて約15%および45%を観察することができる。これらの結果は、抗菌活性が銀金属ではなく銀イオンによって引き起こされる銀イオン抗菌活性と一致する。加えて、菌株のタイプに関して興味深い抵抗作用を観察することができ、グラム陽性はおそらく細胞壁の障壁効果によってグラム陰性よりも抵抗力が高かったことが示される。
表面の水接触角(WCA)に及ぼす銀コーティングの影響
図で観察することができるように、銀コーティングしたシリコーンサンプルは、水で処理した場合、非修飾シリコーンの75°とは対照的に、WCAが100℃以上に増加することを示している。加えて、銀コーティングサンプルは、ムチンで処理した場合に同様の挙動を示し、100℃付近へのWCAの上昇を観察することができる。それらの表面のこの疎水性の増加は、細菌付着を減少させる防汚表面として作用することによって銀コーティングサンプルの抗菌効果を最大にするために、非常に興味深い。
ナノ粒子
図5は、異なるヒト細胞系統を用いたパクリタキセル担持ナノ粒子の抗増殖効果のin vitroアッセイを示している。ヒト正常肺繊維芽細胞(IMR−90)では、薬物非担持のナノ粒子は細胞生存率のわずかな低下を示すが、パクリタキセル担持ナノ粒子ではその効果はより劇的であることが観察された。狭窄性繊維芽細胞をナノ粒子で処理した場合には同じプロフィールが観察される。結論として、両方の場合において、薬物を含まないナノ粒子は、ナノ粒子ポリマーの生体適合性を確認する明らかな細胞毒性を示さなかった。しかしながら、14nMを超える薬物総量を有する両方の薬物担持ナノ粒子(1%および3%)は、培地中へのパクリタキセルの放出に関連する細胞生存率の低下を示した(IMR−90の場合、1%および3%について、両方約80%;狭窄性繊維芽細胞の場合、1%および3%についてはそれぞれ70%および80%);(10nMおよび20nMは同じ結果を示す)。さらに、この処理の間に、培地へのパクリタキセルの蓄積によって引き起こされる細胞生存率の漸減が観察され、その結果、薬物濃度は総量14nMに増加した。加えて、薬物担持ナノ粒子での処理を純粋パクリタキセルと比較すると、同様の挙動を観察することができるが、薬物担持ナノ粒子が細胞毒性効果を向上させ、培地中でのパクリタキセルの作用によって引き起こされる細胞の生存率低下が裏付けられるものと理解することができる。最後に、IMR−90および狭窄性繊維芽細胞、両方の場合において、細胞生存率は、著しい細胞減少を引き起こすパクリタキセルの特異的効果によって非常に影響を受けると結論付けることができる。
Claims (19)
- 支持体を金属でコーティングするための方法であって、
(i)前記支持体の少なくとも第1の表面を、活性化されたカルボキシル基を含有する反応性モノマーと、前記モノマーの重合による前記支持体の前記表面上での前記活性化されたカルボキシル基を含有するポリマーコートの形成に十分な条件下で接触させる工程、
(ii)工程(i)で得られた前記支持体を、前記活性化されたカルボキシル基と反応性の基を含んでなる還元性炭水化物と、前記炭水化物中の前記反応性の基と前記支持体の前記表面上の前記活性化されたカルボキシル基との間の共有結合の形成に十分な条件下で接触させ、それによって、還元性炭水化物で修飾された表面を得る工程、および
(iii)工程(ii)で得られた前記支持体を、前記金属由来の金属性イオンの塩と、前記還元性炭水化物による前記金属性イオンの還元および前記表面上への金属の形態の前記イオンの堆積に十分な条件下で接触させ、それによって、金属コーティングされた表面を得る工程
を含む、方法。 - 前記支持体がシリコーン系ポリマーである、請求項1に記載の方法。
- 前記シリコーン系ポリマーがポリジメチルシロキサンである、請求項2に記載の方法。
- 前記活性化されたカルボキシル基と反応性の前記基がアミノ基であり、かつ、前記炭水化物中の前記アミノ基と前記支持体の前記表面上の前記活性化されたカルボキシル基との間の前記共有結合がアミド結合である、請求項1〜3のいずれか一項に記載の方法。
- 反応性カルボキシル基を含有する前記反応性モノマーが活性化されたメタクリレートである、請求項1〜4のいずれか一項に記載の方法。
- 活性化基がペンタフルオロフェニル基である、請求項5に記載の方法。
- 工程(i)における前記接触が化学蒸着を用いて行われる、請求項1〜6のいずれか一項に記載の方法。
- 前記化学蒸着がプラズマ強化化学蒸着(PECVD)である、請求項7に記載の方法。
- 前記金属性イオンが銀イオンである、請求項1〜8のいずれか一項に記載の方法。
- 前記銀イオンがジアミン−銀(I)錯体イオンとして提供される、請求項9に記載の方法。
- 前記ジアミン−銀(I)錯体が硝酸銀アンモニウムである、請求項10に記載の方法。
- 反応性の基を含んでなる前記還元性炭水化物がN−グルコサミンである、請求項1〜11のいずれか一項に記載の方法。
- 工程(i)が前記支持体の少なくとも第2の表面にも適用され、前記第2の表面が、前記活性化されたカルボキシル基と反応性の基で修飾された粒子と接触させられ、前記粒子が、ナノ粒子およびマイクロ粒子から選択され、前記粒子が、少なくとも治療上活性である化合物を含有し、かつ、前記接触が、前記粒子中の前記反応性の基と前記支持体の前記表面上の前記活性化されたカルボキシル基との間の共有結合の形成に十分な条件下で行われ、それによって、粒子で修飾された前記第2の表面の修飾がもたらされる、請求項1〜12のいずれか一項に記載の方法。
- 前記治療上活性である化合物が、抗増殖性化合物、抗遊走性化合物、抗血管形成性化合物、抗炎症性化合物、細胞増殖抑制性化合物、細胞傷害性化合物、抗血栓性活性剤および上記の1つ以上の組合せからなる群から選択される、請求項13に記載の方法。
- 請求項1〜14のいずれか一項に記載の方法によって得ることができる支持体。
- ステントである、請求項15に記載の支持体。
- 第1の表面が金属性コートでコーティングされており、第2の表面が粒子でコーティングされており、前記金属性コートを有する前記表面が内側表面であり、前記粒子コートを有する前記表面が外側表面である、請求項16に記載のステント。
- 冠動脈ステント、血管ステント、気管ステント、気管支ステント、尿道ステント、食道ステント、胆道ステント、腎臓ステント、小腸における使用のためのステント、大腸における使用のためのステント、喉頭インプラント、バイパス、カテーテルまたは回腸人工肛門である、請求項15〜17のいずれか一項に記載のステント。
- 狭窄、再狭窄、動脈硬化症、アテローム性動脈硬化症、血管閉塞、血管収縮、動脈瘤の予防、軽減または治療における使用、ならびに、人工的な開口部およびアクセスのための使用のための、請求項18に記載のステント。
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