JP2008525588A - フッ化モノマーおよび炭化水素モノマーのポリマー - Google Patents
フッ化モノマーおよび炭化水素モノマーのポリマー Download PDFInfo
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Abstract
Description
本発明は一般に、ステントなどの埋込型装具をコーティングするのに有用なポリマー材料に関する。
[背景の説明]
ステントは機械的には良好に機能するが、再狭窄、および程度は低いがステント血栓症の、慢性的問題が残っている。薬物送達ステント方式での薬物治療は、これら生物学的に由来した問題に取り組むための実行可能な手段に見える。ステント上へ配置されたポリマーコーティングは、薬物貯蔵として働き、かつ薬物の放出を制御するという両方の働きをする。ポリマーをコーティングした市販の製品の1つが、Boston Scientific社製造のステントである。例えば、Boston Scientific Corporationに譲渡された米国特許第5869127号、第6099563号、第6179817号、および第6197051号明細書に、医療装具をコーティングする種々の組成物が記述されている。これらの組成物は、そこに記述されたステントに向上した生体適合性を付与し、場合によっては生理活性剤を含んでもよい。Scimed Life Systems Inc.の米国特許第6231590号明細書には、生理活性剤、コラーゲン材料を含むコーティング組成物、または場合により他の生理活性剤を含み、または他の生理活性剤でコーティングしてあるコラーゲンコーティングが記述されている。
[発明の概要]
本発明では、ステントなどの埋込型装具をコーティングするのに有用な、フッ化モノマーおよび炭化水素モノマーを含むポリマーを提供する。フッ化モノマーは、ポリマーに機械的強度を付与することができる。本明細書に記載の炭化水素モノマーは、ポリマーにたわみ性を与える。
一実施形態では、該ポリマーは、下記に示すような一般式(式I)を有するランダムまたはブロックポリマーであってよい。
別の実施形態では、式I〜IIIのポリマーは、埋込型装具のためのコーティング材を形成するために、別の生体適合性ポリマーとブレンドできる。生体適合性ポリマーは、生物分解性または非分解性でよい。これら生体適合性ポリマーの代表的な例としては、限定はされないが、ポリ(エステルアミド)、ポリエステル、ポリヒドロキシアルカノエート(PHA)、ポリ(3−ヒドロキシプロパノエート)、ポリ(3−ヒドロキシブチレート)、ポリ(3−ヒドロキシバレレート)、ポリ(3−ヒドロキシヘキサノエート)、ポリ(3−ヒドロキシヘプタノエート)、およびポリ(3−ヒドロキシオクタノエート)などのポリ(3−ヒドロキシアルカノエート)、ポリ(4−ヒドロキシブチレート)、ポリ(4−ヒドロキシバレレート)、ポリ(4−ヒドロキシヘキサノート)、ポリ(4−ヒドロキシヘプタノエート)、ポリ(4−ヒドロキシオクタノエート)、および本明細書に記載の3−ヒドロキシアルカノエートまたは4−ヒドロキシアルカノエートモノマーあるいはそれらの混合物のいずれかを含むコポリマーなどのポリ(4−ヒドロキシアルカノエート(alknaotes))、ポリ(D,L−ラクチド)、ポリ(L−ラクチド)、ポリグリコリド、ポリ(D,L−ラクチド−co−グリコリド)、ポリ(L−ラクチド−co−グリコリド)、ポリカプロラクトン、ポリ(ラクチド−co−カプロラクトン)、ポリ(グリコリド−co−カプロラクトン)、ポリ(ジオキサノン)、ポリ(オルトエステル)、ポリ(酸無水物)、ポリ(チロシンカーボネート)およびその誘導体、ポリ(チロシンエステル)およびその誘導体、ポリ(イミノカーボネート)、ポリ(グリコール酸−co−トリメチレンカーボネート)、ポリリン酸エステル、ポリリン酸エステルウレタン、ポリ(アミノ酸)、ポリシアノアクリレート、ポリ(トリメチレンカーボネート)、ポリ(イミノカーボネート)、ポリウレタン、ポリホスファゼン、シリコーン、ポリオレフィン、ポリイソブチレンおよびエチレン−αオレフィンコポリマー、ポリ(メチルメタクリレート)、ポリ(エチルメタクリレート)、ポリ(イソプロピルメタクリレート)、ポリ(n−プロピルメタクリレート)、ポリ(n−ブチルメタクリレート)、メタクリルポリマーおよびコポリマー、アクリルポリマーおよびコポリマー、ポリ塩化ビニルなどのハロゲン化ビニルポリマーおよびコポリマー、ポリ(フッ化ビニリデン)、ポリ(フッ化ビニリデン−co−ヘキサフルオロプロピレン)、ポリビニルメチルエーテルなどのポリビニルエーテル、ポリ塩化ビニリデンなどのポリハロゲン化ビニリデン、ポリアクリロニトリル、ポリビニルケトン、ポリスチレンなどのポリビニル芳香族、ポリ酢酸ビニルなどのポリビニルエステル、エチレン−メチルメタクリレートコポリマー、アクリロニトリル−スチレンコポリマー、ABS樹脂、およびエチレン−酢酸ビニルコポリマーなどのビニルモノマー同士およびオレフィンとのコポリマー、ナイロン66およびポリカプロラクタムなどのポリアミド、アルキド樹脂、ポリカーボネート、ポリオキシメチレン、ポリイミド、ポリエーテル、ポリ(グリセリルセバケート)、ポリ(プロピレンフマレート)、エポキシ樹脂、ポリウレタン、レーヨン、レーヨン−トリアセテート、セルロースアセテート、セルロースブチレート、セルロースアセテートブチレート、セロハン、硝酸セルロース、セルロースプロピオネート、セルロースエーテル、カルボキシメチルセルロース、ポリ(エチレングリコール)(PEG)などのポリエーテル、コポリ(エーテル−エステル)、例えばコポリ(エチレンオキシド−co−乳酸)(PEO/PLA)、ポリ(エチレンオキシド)およびポリ(プロピレンオキシド)などのポリアルキレンオキシド、ポリアルキレンオキサレート、ホスホリルコリン、コリン、ポリ(アスピリン)、ヒドロキシエチルメタクリレート(HEMA)、ヒドロキシプロピルメタクリレート(HPMA)、ヒドロキシプロピルメタクリルアミド、PEGアクリレート(PEGA)、PEGメタクリレート、2−メタクリロイルオキシエチルホスホリルコリン(MPC)およびn−ビニルピロリドン(VP)などの水酸基を有するモノマーのポリマーおよびコポリマー、メタクリル酸(MA)、アクリル酸(AA)、アルコキシメタクリレート、アルコキシアクリレート、および3−トリメチルシリルプロピルメタクリレート(TMSPMA)などのカルボン酸を有するモノマー、ポリ(スチレン−イソプレン−スチレン)−PEG(SIS−PEG)、ポリスチレン−PEG、ポリイソブチレン−PEG、ポリカプロラクトン−PEG(PCL−PEG)、PLA−PEG、ポリ(メチルメタクリレート)−PEG(PMMA−PEG)、ポリジメチルシロキサン−co−PEG(PDMS−PEG)、ポリ(フッ化ビニリデン)−PEG(PVDF−PEG)、PLURONIC(商標)界面活性剤(ポリプロピレンオキシド−co−ポリエチレングリコール)、ポリ(テトラメチレングリコール)、ヒドロキシ官能性ポリ(ビニルピロリドン)、コラーゲン、キトサン、アルギネート、フィブリン、フィブリノゲン、セルロース、スターチ、コラーゲン、デキストラン、デキストリン、ヒアルロン酸の断片および誘導体、ヘパリン、ヘパリンの断片および誘導体、グリコサミノグリカン(GAG)、GAG誘導体、多糖類、エラスチン、キトサン、アルギネートなどの生体分子およびそれらの組合せなどが挙げられる。いくつかの実施形態では、ポリマーは前述のポリマーのいずれか1つを除外することができる。
本発明のさらなる一実施形態に従って、本明細書に記載のポリマーまたはポリマーブレンドは、1つまたは複数の活性剤を任意に含めてよいコーティングを形成することができる。生理活性剤は、生物学的に活性であるいずれかの作用物質、例えば、治療薬、予防薬、または診断薬でよい。
本明細書で使用する場合、埋込型装具は、ヒトまた動物の患者に埋め込むことができる、任意の適切な医療基材でよい。こうした埋込型装具の例としては、自動拡張型ステント、バルーン拡張型ステント、ステントグラフト、移植片類(例えば、大動脈グラフト)、人工心臓弁、卵円孔開存用閉鎖装置、脳脊髄液シャント、ペースメーカーの電極、および心内膜リード(例えば、Guidant Corporation社、Santa Clara、CA.から入手可能なFINELINEおよびENDOTAK)が挙げられる。該装具の下部構造は、実質的にはいずれの設計のものでもよい。該装具は、限定はされないが、コバルトクロム合金(ELGILOY)、ステンレス鋼(316L)、高窒素ステンレス鋼、例えば、BIODUR108、コバルトクロム合金L−605、「MP35N」「MP20N」ELASTINITE(ニチノール)、タンタル、ニッケル−チタンの合金、白金−イリジウムの合金、金、マグネシウム、またはそれらの組合せなどの金属材料または合金で作製することができる。「MP35N」および「MP20N」は、Standard Press Steel Co.社 Jenkintown、PAから入手可能な、コバルト、ニッケル、クロム、およびモリブデンの合金類の商品名である。「MP35N」はコバルト35%、ニッケル35%、クロム20%、およびモリブデン10%から成る。「MP20N」は、コバルト50%、ニッケル20%、クロム20%、およびモリブデン10%から成る。生体吸収性または生体安定性のポリマーから作製された装具は、本発明の実施形態でも使用することができる。
本発明の実施形態に従い、様々な前記実施形態のコーティングを、埋込型装具または補綴物、例えばステント上に形成することができる。1つまたは複数の活性剤を含むコーティングでは、薬剤は送達中、および装具の膨張中にステントなどの医療用具上に保持され、埋め込み部位に所望の速度で所定の持続時間放出されることとなる。医療用具はステントが好ましい。上記コーティングを有するステントは、一例として、胆管、食道、気管/気管支、および他の生体通路内で腫瘍が引き起こす閉塞症の治療を含み、種々の医療手順に有用である。上記コーティングを有するステントは、平滑筋細胞の異常または不適当な遊走および増殖、アテローム硬化症、血栓症、および再狭窄により引き起こされる血管の閉塞領域を治療するために、特に有用である。ステントは、動脈と静脈両方の多様な血管に設置することが可能である。部位の代表的な例としては、腸骨、腎臓、頸動脈、および冠血管の動脈が挙げられる。
実施例1:ポリ(ブロック−フッ化ビニリデン−co−ブロック−イソブチレン)の合成
フルオロポリマーは一般に、懸濁液またはエマルジョン法を用いて、ラジカル重合により合成され、一方ポリイソブチレンは一般に、カチオン重合法を経て生成される(G.Odian著、Principles of Polymerization、第3版、John Wiley&Sons社、NY、1991年参照)。しかしフルオロポリマーは、ヨウ素または臭素の官能性開始剤を使用し、原子移動ラジカル重合(ATRP)によっても合成できる。これら重合の結果、末端ヨウ素基または末端臭素基を有するPVDFとなる。次いでこれらの末端基は、直接使用されるかまたは官能化し、イソブチレンのカルボカチオン開始剤として働くことができる。ブロックコポリマーは、ATRP技術によってブロモ末端ポリ(フッ化ビニリデン)を最初に合成することにより、作製することができる(Z.Zhangら著、「Synthesis of fluorine−containing block copolymers via ATRP 1、Synthesis and characterization of PSt−PVDF−PSt triblock copolymers」Polymer(40)(1999)1341−1345を参照)。得られたブロモ末端PVDFは、四塩化チタン、四臭化チタン、または三塩化アルミニウムなどのルイス酸を触媒とするカチオン重合で、開始剤として使用することができる(J.P.Kennedyら著、「Design Polymers by carbocationic Macromolecular Engineering」Hanser出版、NY、Munich、1992を参照)。フッ化ビニリデン対イソブチレンの有用な重量比は75/25である。
両モノマーは、ラジカル重合を受け易い。この重合は、懸濁または乳化重合の技術によって可能になる。有用な開始剤は、過酸化物、可溶性有機過酸化物、過硫酸化合物、およびアゾ化合物である。第一鉄、亜硫酸、または亜硫酸水素のイオンを含む化合物などのレドックス系は、低温度で所望の開始速度を実現するのに使用することができる。有用な1手段は、オートクレーブ内での懸濁重合である。フッ化ビニリデン/スチレンコポリマー分散は、フッ化ビニリデン90重量%およびスチレン10重量%の組成で、調製することができる。10ガロンのグラスライニング製オートクレーブに、脱イオン水5ガロンを添加し、フッ化ビニリデン(VDF)2.2kgおよびスチレン0.24kgを注入する。窒素を散布して全酸素を取り除き、高速攪拌した後、脱イオン水で100mlに希釈した第三級ブチルヒドロペルオキシド(TBHP)70%溶液20gの溶液を添加する。次いで、脱イオン水100mlに溶解した、メタ重亜硫酸ナトリウム(MBS)15gおよび硫酸第一鉄・七水和物2.2gの溶液を添加する。オートクレーブを15〜20℃に保持する。開始触媒の添加後、過フッ化アンモニウムオクトアネート(octoanate)触媒(活性固体20%)300mlをオートクレーブに注入する。脱イオン水で700mlに希釈したTBHP100g、および脱イオン水で750mlに希釈したMBS80gからなる2つの別個の溶液をゆっくりと添加することにより、重合を継続させる。これら開始剤を1:8ml/分の速さで添加する。VDFおよびスチレンの初期投与量を消費後、VDF18kgおよびスチレン2kgを、5時間かけて添加する。オートクレーブを開栓し、ポリマー分散水を生成し、それをふるいにかけて分離し、濯ぐ。
下記成分を混合することにより、組成物を調製できる。
(a)実施例2のポリマー約2.0%(w/w)、
(b)エバロリムス約1.0%(w/w)、
(c)バランスが50/50(w/w)のアセトンとジメチルホルムアミドのブレンド。
Claims (26)
- フッ化モノマーおよび炭化水素モノマーを含む生体適合性ポリマーであって、
前記フッ化モノマーが、前記ポリマーの反復単位約25.01モル%〜約99.99モル%を形成し、
前記炭化水素モノマーが、前記ポリマーの反復単位約74.99モル%〜約0.01モル%を形成する、
生体適合性ポリマー。 - フッ化モノマーおよび炭化水素モノマーを含む生体適合性ポリマーであって、
前記フッ化モノマーが、前記ポリマーの単位約50.01モル%〜約94.99モル%を形成し、
前記炭化水素モノマーが、前記ポリマーの反復単位約49.99モル%〜約5.01モル%を形成する、
生体適合性ポリマー。 - 前記フルオロモノマーが、−CF2−CF2−、−CH2−CF2−、−CH2−CHF−、−CHF−CHF−、−CClF−CF2−、−CF2−C(CF3)F−、−CHF−C(CF3)F−、−CF2−C(CF3)H−、−CF2−CRF−、−CHF−CRF−、−CF2−CRH−、−CH2−CRF−、および−CFH−CRH−、(式中Rは、水素、Cl、Br、I、メチル、エチル、n−プロピル、イオソ(ioso)プロピル、短鎖アルキル基、フェニル、置換フェニル、環状アルキル、複素環、ヘテロアリール、短鎖フッ化アルキル基、フッ化フェニル、環状フッ化アルキル、フッ化複素環)からなる群またはそれらの組合せから選択され、
前記炭化水素モノマーが、CHR=CH2またはCR2=CH2、(式中Rが水素、メチル、エチル、n−プロピル、イソプロピル、短鎖アルキル基、フェニル、置換フェニル、環状アルキル、複素環、ヘテロアリール)またはそれらの組合せとなり得る、
請求項3に記載の生体適合性ポリマー。 - 前記炭化水素モノマーが、1つまたは複数のイソブチレン、スチレン、メチルスチレン、アルキル置換スチレン、エチレン、プロピレン、およびブチレン類である、請求項3に記載の生体適合性ポリマー。
- 請求項1に記載の生体適合性ポリマーおよび少なくとも1種の他の生体適合性ポリマーを含む、生体適合性ポリマーブレンド。
- 請求項3に記載の生体適合性ポリマーおよび少なくとも1種の他の生体適合性ポリマーを含む、生体適合性ポリマーブレンド。
- 請求項4に記載の生体適合性ポリマーおよび少なくとも1種の他の生体適合性ポリマーを含む、生体適合性ポリマーブレンド。
- 前記他の生体適合性ポリマーが、ポリ(エステルアミド)、ポリエステル、ポリヒドロキシアルカノエート(PHA)、ポリ(3−ヒドロキシアルカノエート)、ポリ(3−ヒドロキシプロパノエート)、ポリ(3−ヒドロキシブチレート)、ポリ(3−ヒドロキシ吉草酸)、ポリ(3−ヒドロキシヘキサノエート)、ポリ(3−ヒドロキシヘプタノエート)、ポリ(3−ヒドロキシオクタノエート)、ポリ(4−ヒドロキシアルカノエート)、ポリ(4−ヒドロキシブチレート)、ポリ(4−ヒドロキシ吉草酸)、ポリ(4−ヒドロキシヘキサノート)、ポリ(4−ヒドロキシヘプタノエート)、本明細書に記載の3−ヒドロキシアルカノエート、4−ヒドロキシアルカノエートのモノマーまたはそれらのブレンドを含むポリ(4−ヒドロキシオクタノエート)コポリマー、ポリ(D,L−ラクチド)、ポリ(L−ラクチド)、ポリグリコリド、ポリ(D,L−ラクチド−co−グリコリド)、ポリ(L−ラクチド−co−グリコリド)、ポリカプロラクトン、ポリ(ラクチド−co−カプロラクトン)、ポリ(グリコリド−co−カプロラクトン)、ポリ(ジオキサノン)、ポリ(オルトエステル)、ポリ(酸無水物)、ポリ(チロシンカーボネート)およびその誘導体、ポリ(チロシンエステル)およびその誘導体、ポリ(イミノカーボネート)、ポリ(グリコール酸−co−トリメチレンカーボネート)、ポリリン酸エステル、ポリリン酸エステルウレタン、ポリ(アミノ酸)、ポリシアノアクリレート、ポリ(トリメチレンカーボネート)、ポリ(イミノカーボネート)、ポリウレタン、ポリホスファゼン、シリコーン、ポリオレフィン、ポリイソブチレンおよびエチレン−αオレフィンコポリマー、メタクリルポリマーおよびコポリマー、アクリルポリマーおよびコポリマー、ポリ(メチルメタクリレート)、ポリ(エチルメタクリレート)、ポリ(イソプロピルメタクリレート)、ポリ(n−プロピルメタクリレート)、ポリ(n−ブチルメタクリレート)、ハロゲン化ビニルポリマーおよびコポリマー、ポリ塩化ビニル、ポリ(フッ化ビニリデン)、ポリ(フッ化ビニリデン−co−ヘキサフルオロプロピレン)、ポリビニルエーテル、ポリビニルメチルエーテル、ポリハロゲン化ビニリデン、ポリ塩化ビニリデン、ポリアクリロニトリル、ポリビニルケトン、ポリビニル芳香族、ポリスチレン、ポリビニルエステル、ポリ酢酸ビニル、ビニルモノマーのコポリマー、エチレン−メチルメタクリレートコポリマー、アクリロニトリル−スチレンコポリマー、ABS樹脂、およびエチレン酢酸ビニルコポリマー、ポリアミド、ナイロン66およびポリカプロラクタム、アルキド樹脂、ポリカーボネート、ポリオキシメチレン、ポリイミド、ポリエーテル、ポリ(グリセリルセバケート)、ポリ(プロピレンフマレート)、エポキシ樹脂、ポリウレタン、レーヨン、レーヨン−トリアセテート、セルロースアセテート、セルロースブチレート、セルロースアセテートブチレート、セロハン、硝酸セルロース、セルロースプロピオネート、セルロースエーテル、カルボキシメチルセルロース、ポリエーテル、ポリ(エチレングリコール)(PEG)、コポリ(エーテルエステル)、コポリ(エチレンオキシド−co−乳酸)(PEO/PLA)、ポリアルキレンオキシド、ポリ(エチレンオキシド)、ポリ(プロピレンオキシド)、ポリアルキレンオキサレート、ホスホリルコリン、コリン、ポリ(アスピリン)、ヒドロキシルを含有するモノマーのポリマーおよびコポリマー、ヒドロキシエチルメタクリレート(HEMA)のポリマーおよびコポリマー、ヒドロキシプロピルメタクリレート(HPMA)のポリマーおよびコポリマー、ヒドロキシプロピルメタクリルアミドのポリマーおよびコポリマー、PEGアクリレート(PEGA)のポリマーおよびコポリマー、PEGメタクリレートのポリマーおよびコポリマー、2−メタクリロイルオキシエチルホスホリルコリン(MPC)のポリマーおよびコポリマー、n−ビニルピロリドン(VP)のポリマーおよびコポリマー、カルボン酸を含有するモノマーのポリマーおよびコポリマー、メタクリル酸(MA)のポリマーおよびコポリマー、アクリル酸(AA)のポリマーおよびコポリマー、アルコキシメタクリレートのポリマーおよびコポリマー、アルコキシアクリレートのポリマーおよびコポリマー、3−トリメチルシリルプロピルメタクリレート(TMSPMA)のポリマーおよびコポリマー、ポリ(スチレン−イソプレン−スチレン)−PEG(SIS−PEG)、ポリスチレン−PEG、ポリイソブチレン−PEG、ポリカプロラクトン−PEG(PCL−PEG)、PLA−PEG、ポリ(メチルメタクリレート)−PEG(PMMA−PEG)、ポリジメチルシロキサン−co−PEG(PDMS−PEG)、ポリ(フッ化ビニリデン)−PEG(PVDF−PEG)、PLURONIC(商標)界面活性剤(ポリプロピレンオキシド−co−ポリエチレングリコール)、ポリ(テトラメチレングリコール)、ヒドロキシ官能性ポリ(ビニルピロリドン)、バイオ分子、コラーゲン、キトサン、アルギネート、フィブリン、フィブリノゲン、セルロース、スターチ、コラーゲン、デキストラン、デキストリン、ヒアルロン酸の断片および誘導体、ヘパリン、ヘパリンの断片および誘導体、グリコサミノグリカン(GAG)、GAG誘導体、多糖類、エラスチン、キトサン、アルギネート、ならびにそれらの組合せからなる群から選択される、請求項9に記載のポリマーブレンド。
- 請求項1に記載の生体適合性ポリマーを含む生体適合性コーティングをその上に有する埋込型装具。
- 請求項2に記載の生体適合性ポリマーを含む生体適合性コーティングをその上に有する埋込型装具。
- 請求項3に記載の生体適合性ポリマーを含む生体適合性コーティングをその上に有する埋込型装具。
- 請求項4に記載の生体適合性ポリマーを含む生体適合性コーティングをその上に有する埋込型装具。
- 請求項5に記載の生体適合性ポリマーを含む生体適合性コーティングをその上に有する埋込型装具。
- 請求項6に記載の生体適合性ポリマーを含む生体適合性コーティングをその上に有する埋込型装具。
- 請求項7に記載の生体適合性ポリマーブレンドを含む生体適合性コーティングをその上に有する埋込型装具。
- 請求項10に記載の生体適合性ポリマーブレンドを含む生体適合性コーティングをその上に有する埋込型装具。
- 前記コーティングがさらに生理活性剤を含む薬物送達ステントである、請求項13に記載の埋込型装具。
- 前記生理活性剤が、パクリタキセル、ドセタキセル、エストラジオール、一酸化窒素供与体、スーパーオキシドジスムターゼ、スーパーオキシドジスムターゼ模倣剤、4−アミノ−2,2,6,6−テトラメチルピペリジン−1−オキシル(4−アミノ−TEMPO)、タクロリムス、デキサメタゾン、ラパマイシン、ラパマイシン誘導体、40−O−(2−ヒドロキシ)エチル−ラパマイシン(エベロリムス)、40−O−(3−ヒドロキシ)プロピル−ラパマイシン、40−O−[2−(2−ヒドロキシ)エトキシ]エチル−ラパマイシン、および40−O−テトラゾール−ラパマイシン、ABT−578、クロベタゾール、それらのプロドラッグ、それらの補助薬、ならびにそれらの組合せからなる群から選択される、請求項19に記載の薬物送達ステント。
- 請求項1に記載の組成物を含む材料から形成されるステント。
- 請求項3に記載の組成物を含む材料から形成されるステント。
- 請求項10に記載の組成物を含む材料から形成されるステント。
- さらに生理活性剤を含む請求項23に記載のステント。
- 請求項13に記載の埋込型装具を患者に埋め込むステップを含む、患者の疾患を治療する方法であって、
前記疾患が、アテローム硬化症、血栓症、再狭窄、出血、血管解離または穿孔、血管動脈瘤、不安定プラーク、慢性完全閉塞、跛行、静脈および人工移植片に対する吻合部増殖、胆管閉塞、尿管閉塞、腫瘍閉塞、ならびにそれらの組合せからなる群から選択される方法。 - 請求項20に記載の埋込型装具を患者に埋め込むステップを含む、患者の疾患を治療する方法であって、
前記疾患が、アテローム硬化症、血栓症、再狭窄、出血、血管解離または穿孔、血管動脈瘤、不安定プラーク、慢性完全閉塞、跛行、静脈および人工移植片に対する吻合部増殖、胆管閉塞、尿管閉塞、腫瘍閉塞、ならびにそれらの組合せからなる群から選択される方法。
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US20130330392A1 (en) | 2013-12-12 |
WO2006069010A2 (en) | 2006-06-29 |
US20130330393A1 (en) | 2013-12-12 |
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US8529930B2 (en) | 2013-09-10 |
US9320833B2 (en) | 2016-04-26 |
US8529931B2 (en) | 2013-09-10 |
US9220816B2 (en) | 2015-12-29 |
US20100004396A1 (en) | 2010-01-07 |
JP5258300B2 (ja) | 2013-08-07 |
US9220815B2 (en) | 2015-12-29 |
US20130324637A1 (en) | 2013-12-05 |
US9289535B2 (en) | 2016-03-22 |
US20070191561A1 (en) | 2007-08-16 |
US8524266B2 (en) | 2013-09-03 |
EP1833526B1 (en) | 2011-11-09 |
ES2374386T3 (es) | 2012-02-16 |
ATE532542T1 (de) | 2011-11-15 |
US20100003303A1 (en) | 2010-01-07 |
US7604818B2 (en) | 2009-10-20 |
US20140005334A1 (en) | 2014-01-02 |
WO2006069010A3 (en) | 2007-02-08 |
DK1833526T3 (da) | 2012-01-23 |
US20100003231A1 (en) | 2010-01-07 |
US20060134165A1 (en) | 2006-06-22 |
US9339592B2 (en) | 2016-05-17 |
EP1833526A2 (en) | 2007-09-19 |
US8529932B2 (en) | 2013-09-10 |
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