JP2009530039A - 医療デバイスを介した高親油性薬剤の送達 - Google Patents
医療デバイスを介した高親油性薬剤の送達 Download PDFInfo
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- JP2009530039A JP2009530039A JP2009501580A JP2009501580A JP2009530039A JP 2009530039 A JP2009530039 A JP 2009530039A JP 2009501580 A JP2009501580 A JP 2009501580A JP 2009501580 A JP2009501580 A JP 2009501580A JP 2009530039 A JP2009530039 A JP 2009530039A
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- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
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- 230000002588 toxic effect Effects 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- 150000005671 trienes Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 1
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
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Abstract
【選択図】 図2
Description
[01]本出願は、2004年3月9日に出願した米国特許出願第10/796,243号の一部継続出願であり、これは2003年3月10日に出願した米国特許出願第60/453,555号の優先権を主張し、また本出願は、2004年10月29日に出願した米国特許出願第10/977,288号の一部継続出願であり、またこれは、2002年9月6日に出願した米国特許出願第10/235,572号の一部継続出願であり、またこれは、現在は米国特許第6,890,546号である、2001年9月10日に出願した米国特許出願第09/950,307号の一部継続出願であり、またこれは、現在は米国特許第6,329,386号である、1999年11月2日に出願した米国特許出願第09/433,001号の一部継続出願であり、またこれは、現在は米国特許第6,015,815号である、1998年9月24日に出願した米国特許出願第09/159,945号の分割出願であり、1997年9月26日に出願した米国特許出願第60/060,015号の優先権を主張し、本出願は、さらに、2005年3月23日に出願した米国特許出願第60/664,328号、2005年10月14日に出願した米国特許出願第60/727,080号、2005年10月14日に出願した米国特許出願第60/726,878号、2005年10月17日に出願した米国特許出願第60/732,577号、及び2005年10月14日に出願した米国特許出願第60/727,196号の優先権を主張し、上記の出願はすべて参照により本明細書に組み込まれる。
[02]本発明は、医療デバイスを使用する高親油性薬剤、より具体的には、少なくとも約5,000(μg/mL)−1の移動係数を有する親油性薬剤の遠隔薬物送達の装置、システム、及び方法に関する。
[03]化合物シクロスポリン(シクロスポリンA)は、臓器移植及び免疫調節の分野に導入されて以来、汎用されており、移植術に成功率の大幅な増加をもたらした。近年、強力な免疫調節活性を有する大環状化合物が数種類発見された。Okuharaらは、1986年6月11日に公開された欧州特許出願第184,162号において、ストレプトミセス・ツクバエンシスの株から単離された、23員大環状ラクトンである免疫抑制剤FK−506を含む、ストレプトミセス属から単離された多数の大環状化合物を開示している。
[22]本発明は、親油性薬剤を送達するためのシステムであって、医療デバイスと、体腔に浸透することができる第1の親油性薬剤であり、その移動係数が少なくとも約5,000(μg/mL)−1の量あり、医療デバイスに関連(associate)する、親油性薬剤とを備え、第1の親油性薬剤/医療デバイスが前記体腔内に隣接して留置され、治療有効量の第1の親油性薬剤が対象体内の所望の領域に送達される、システムに関する。
[61]本発明は、親油性薬剤を体腔に送達するための装置、方法、及び薬物送達システムに関する。本発明の一態様は、親油性薬剤を送達するためのシステムであって、医療デバイスと、体腔に浸透することができる第1の親油性薬剤であり、その移動係数が少なくとも約5,000(μg/mL)−1の量あり、医療デバイスに関連する、親油性薬剤とを備え、第1の親油性薬剤/医療デバイスが前記体腔内に隣接して留置され、治療有効量の第1の親油性薬剤が対象体内の所望の領域に送達される、システムに関する。
[66]本明細書及び付属の請求項で使用されているように、単数形で表されている用語(原文において「a」、「an」、「the」の冠詞を使用している)は、明示的に、また明確に、1つの指示対象に制限されていない限り、複数の指示対象を含むことに留意されたい。本明細書で使用されている「薬剤」という用語は、「少なくとも1つの薬剤」、「化合物」、又は「少なくとも1つの化合物」と同義であり、少なくとも1つの薬物若しくはコドラッグ、又はそのプロドラッグを意味する。
[75]
[76]
を有するアトラセンタン(ABT−627)を含むエンドセリン受容体拮抗薬、Abbott Laboratories Inc.(イリノイ州ノースシカゴ所在)による、一般式C21H22F3NO8Sを有し、また構造式
[77]
[78]
を有するABT−518などのマトリックスメタロプロテイナーゼ阻害剤、ペルミロラストカリウムニトロプルシドなどの抗アレルギー剤、ホスホジエステラーゼ阻害剤、プロスタグランジン阻害剤、スラミン、セロトニン阻害剤、ステロイド、チオプロテアーゼ阻害剤、トリアゾロピリミジン、及び一酸化窒素がある。
[89]「溶解度」は、医薬品化学で使用される標準的尺度に基づく。オクタノール−水分配係数(P)は、1−オクタノールとH2Oの混合物中の化合物分配の比である。LogPは、分配係数の10を底とする対数である。
[90]
[91]LogP値が約1よりも大きい化合物は、親油性とみなされる(H2Oに比べて1−オクタノールの溶解度が大きい)。さまざまなコンピュータ化プロトコルを使用して、LogP値の計算推定値を求めることができる。このようなコンピュータプログラムの1つに、CambridgeSoftCorporationのChemDraw Pro Version 5.0がある。LogP係数を計算するために、クリッペンのフラグメンテーション法(Crippenら、J.Chem.Inf.Comput.Sci.1987,27,21)を使用することができる。
[130]
[131]
[132]
であり、ゾタロリムスの化学構造式は、
である。
[133]
[174]I.PC1036によるクーポンのコーティング
[175]実験を行う前に、コーティングされたステンレスクーポンを用意した。これらのクーポンは316L電解研磨ステンレスディスク(直径10mm)である。このサイズが選ばれたのは、クーポンの片側の表面積が、15mmオープンセルBiodivYsioステントの表面積に似ているからである。クーポンは、クーポンの片側のマークを引っかいて、コーティングされないクーポンの側を示すことにより用意され、次いでクリーニングされた。クリーニングは、クーポンがジクロロメチレン中で3分間、エタノール中で3分間超音波処理される2段階工程であった。クーポンを室温で乾燥させた。エタノール中でホスホリルコリンポリマーPC1036(Biocompatibles Ltd.(英国、ファーナム、サリー所在)の製品)の濾過された20mg/mLの溶液を使用してクーポンの片側をコーティングした。気密注射筒を使用して20μLのPC溶液をクーポン上に置いて、表面全体がコーティングされるが、ただし、クーポンの側面にこぼれないようにする。クーポンは、最初に空気乾燥させ、次いで、16時間にわたって70℃で硬化させた。次いで、<25KGyでγ線照射のために送った。結果として得られるPCコーティング厚さは、図9A〜Bにグラフで表されているように、ステントの太さに近く、所望の担持薬剤投与量を受け入れるのに十分な厚さであった。図9A〜Bは、電解研磨されたステンレスディスク上のPCコーティング20を有する、コーティングされたステンレスクーポン30の上面及び側面図である。
[177]これらの実験において、有益薬剤をクーポンに担持し、溶出プロフィルを調べた。一般に、以下のような手順である。12個のPCコーティングされたクーポンにそれぞれの薬物を担持させた。薬物の溶液は、100%エタノール中で通常5.0mg/mLであり、使用前に0.45μmのフィルタで濾過された。
[180]薬物毎に、6個のクーポンを使用して、上記の手順により担持された薬物の総量を評価した。これらのクーポンを50%エタノール、50%水の水溶液5mLに浸漬して、1時間かけて超音波処理した。HPLCにより抽出溶液中の薬物の濃度を分析した。
[183]それぞれの薬物の6つのコーティングされたクーポンを溶出実験に使用した。これらのクーポンを個別に、コーティング側を上にして、小さな金属カップ内に入れて、クーポンを保持し、それぞれの時点において新しいバイアル瓶に移動させた。これらのクーポンは、通常、pH7.4のリン酸緩衝生理食塩水10mLを入れたバイアル瓶内に置いた。バイアル瓶をオービタルシェーカー内に保管し、100rpmの水平振盪を少なくとも30分間、37℃の温度で行ってから、クーポンを挿入し、所望の温度で溶液を平衡状態にした。表2に示されているように、少なくとも9つの異なる時点が観察された。所望の時間が経過した後、クーポンホルダを持ち上げて、排出を行った。次いで、次の時点に対応する予熱されているバイアル瓶内に置いた。この手順は、所定の時間が経過するまで続けた。その時点で、クーポンは、前に概要を述べたように薬物抽出工程に通された。HPLCにより溶出試料中の薬物の量を決定した。
[197]I.PC1036によるステントのコーティング
[198]実験を行う前に、コーティングされたステントを用意した。これらは、3.0mm×15mmの316L電解研磨ステンレスステントであった。エタノール中のホスホリルコリンポリマーPC1036(Biocompatibles Ltd.(英国、ファーナム、サリー所在)の製品)の濾過された20mg/mLの溶液を使用してそれぞれのステントを噴霧コーティングした。ステントは、最初に空気乾燥させ、次いで、16時間にわたって70℃で硬化させた。次いで、<25KGyでのγ線照射のために送った。
[200]これらの実験において、有益薬剤をステント内に担持し、溶出プロフィルを調べた。一般に、以下のような手順であった。複数のPCコーティングされたステントにそれぞれの薬物複合溶液を担持させた。これらの薬物の溶液は、通常、100%エタノール中、ゾタロリムス2〜20mg/mL及びデキサメタゾン10.0mg/mLの範囲にあり、膜形成を高めるためにこの溶液に〜10%のPC1036を加えた。
[203]薬物毎に、3個のステントを使用して、上記の手順により担持された薬物の総量を評価した。これらのステントを50%エタノール、50%水の水溶液6mLに浸漬して、20分かけて超音波処理した。HPLCにより抽出溶液中の薬物の濃度を分析した。
[206]溶解溶媒としてpH4の緩衝液であるポリエチレングリコール660の水溶液を使用する溶解研究においてホスホリルコリン(PC)コーティング金属ステント(上述)から溶出されたゾタロリムス及びデキサメタゾンの量を決定するためにHPLC法が開発された。この方法は、選択された時点、典型的には24時間の期間に、37℃でステントから溶解溶媒中に溶出された薬物の量を決定するために使用される。この高速な生体外溶出試験は、製造工程に関する品質検査及びステントからの薬物溶出を制御する因子を理解するための高速な信頼性の高いリサーチツールとして使用することが意図されている。
[223]I.デキサメタゾン/ゾタロリムス/PCコーティングステント
[224]これらの実験において、有益薬剤をステント上に担持し、2つの薬物の安定性を調べた。一般に、以下のような手順であった。複数のPCコーティングされたステントに溶液からのそれぞれの複合薬を担持させた。これらの薬物の溶液は、通常、100%エタノール中、ゾタロリムス2〜20mg/mL及びデキサメタゾン10.0mg/mLの範囲にあり、膜形成を高めるためにこの溶液に〜10%のPC1036を加えた。
[227]薬物担持の後、ステントをカテーテルバルーン上に圧着(crimp)し、ETO(エチレンオキシド)殺菌用の医療用製品タイベックパウチ内にパッケージした。ETO殺菌工程は、医療デバイス業界では製品安全性を保証するための標準である。ETO工程は、微生物及び胞子を確実に殺すために高湿度、高温環境において実行された。
[229]薬物毎に、複数のステントを使用して、上記の手順により担持された薬物の純度及び安定度を評価した。これらのステントを50%エタノール、50%水の水溶液6mLに浸漬して、20分かけて超音波処理した。HPLCにより抽出溶液中の薬物の分解物関連不純物の濃度及び存在を分析した。
[233]本発明の実施形態の化合物及び工程は、本発明の化合物を調製できる方法を例示する以下の合成スキームと併せるとよく理解できる。
[242]前記は、本発明の化合物を調製できる方法を例示する以下の実施例を参照することでよく理解できるが、付属の請求項に定められているような本発明の範囲を制限することを意図されていない。
[244]42−エピ−(テトラゾリル)−ラパマイシン(極性の小さい異性体)
[245]実施例1A
[246]窒素雰囲気下、−78℃の温度のジクロロメタン(0.6mL)中のラパマイシン(100mg、0.11mmol)の溶液を、2,6−ルチジン(53μL、0.46mmol、4.3eq.)及びトリフルオロメタンスルホン酸無水物(37μL、0.22mmol)で順次処理し、その後15分間攪拌し、室温に温めて、ジエチルエーテルを使用してシリカゲル(6mL)のパッドに通して溶出した。トリフラートを含む分画をプールし、濃縮して、示された化合物を琥珀色の発泡体として得た。
[248]42−エピ−(テトラゾリル)−ラパマイシン(極性の小さい異性体)
[249]酢酸イソプロピル(0.3mL)に対する実施例1Aの溶液を、ジイソプロピルエチルアミン(87L、0.5mmol)及び1H−テトラゾール(35mg、0.5mmol)で順次処理し、その後18時間攪拌した。この混合物を、水(10mL)とエーテル(10mL)とに分けた。有機物を塩水(10mL)で洗い、乾燥させた(Na2SO4)。この有機物を濃縮し、ヘキサン(10mL)、ヘキサン:エーテル(4:1(10mL)、3:1(10mL)、2:1(10mL)、1:1(10mL))、エーテル(30mL)、ヘキサン:アセトン(1:1(30mL))で溶出するシリカゲル(3.5g、70〜230メッシュ)上のクロマトグラフィにより精製された粘着性のある黄色の固形物を得た。異性体の1つをエーテル分画中に集めた。
[250]MS(ESI)m/e 966(M)−;
[252]42−エピ−(テトラゾリル)−ラパマイシン(極性の大きい異性体)
[253]実施例2A
[254]42−エピ−(テトラゾリル)−ラパマイシン(極性の大きい異性体)
[255]実施例1Bのヘキサン:アセトン(1:1)移動相を使用してクロマトグラフィカラムからよりゆっくり移動するバンドを回収して、指定化合物を得た。
[256]MS(ESI)m/e 966(M)−
[258]本発明の化合物の免疫抑制剤活性をラパマイシン及び2つのラパマイシン類似体:40−エピ−N−[2’−ピリドン]−ラパマイシン及び40−エピ−N−[4’−ピリドン]−ラパマイシンと比較した。この活性は、Kino,T.ら、Transplantation Proceedings,XIX(5):36−39,Suppl.6(1987)において説明されているヒト混合リンパ球反応(MLR)アッセイを使用して決定された。このアッセイの結果は、本発明の化合物が、表1に示されているように、ナノモル濃度で有効な免疫調節薬であることを示している。
Claims (41)
- 近接する疾患を治療及び/又は予防するか、又は体腔の開通性を維持するために医療デバイスを体腔内に留置することを含む、対象体内の開通性を改善するための方法であって、
医療デバイスを体腔内に準備するステップと、
体腔に浸透することができる第1の親油性薬剤であり、その移動係数が少なくとも約5,000(μg/mL)−1の量であり、前記医療デバイスに関連する、前記親油性薬剤を準備するステップと、
前記第1の親油性薬剤/医療デバイスを体腔に隣接して留置するステップと、
治療有効量の前記第1の親油性薬剤を対象体内の所望の領域に送達するステップとを含む方法。 - 少なくとも1つの薬学的に許容される担体又は賦形剤をさらに備え、前記医療デバイスは前記薬学的に許容される担体又は賦形剤に関連する、請求項1に記載の方法。
- 前記薬学的に許容される担体又は賦形剤はポリマーである、請求項2に記載の方法。
- 前記薬学的に許容される担体又は賦形剤は薬剤である、請求項2に記載の方法。
- 前記体腔は、血管壁、冠状動脈、食道管腔、及び尿道のうちの少なくとも1つを含む、請求項1に記載の方法。
- 前記第1の親油性薬剤/医療デバイスは、冠状動脈を含む前記体腔に隣接して留置され、前記方法において、治療有効量の前記第1の親油性薬剤は前記冠状動脈内に送達され、心膜嚢内に拡散される、請求項1に記載の方法。
- 前記親油性薬剤の心筋への実質的に一様な薬物送達をもたらす、請求項6に記載の方法。
- 対象の血管疾患の治療及び/又は予防に有用である、請求項1に記載の方法。
- 前記第1の親油性薬剤の前記送達機序は、ポリマー水和反応とそれに続く前記第1の親油性薬剤の溶解を含み、その後、前記第1の親油性薬剤は前記体腔内に送達される、請求項3に記載の方法。
- 前記第1の親油性薬剤の前記送達機序は、前記体腔への前記第1の親油性薬剤の溶出速度を制御する親油性薬剤/ポリマーマトリクスを含む、請求項3に記載の方法。
- 少なくとも1つの第2の親油性薬剤をさらに備える、請求項1に記載の方法。
- 少なくとも1つの親油性プロドラッグをさらに備える、請求項1に記載の方法。
- 少なくとも1つの親油性浸透促進剤をさらに備える、請求項1に記載の方法。
- 前記親油性浸透促進剤は医薬品である、請求項13に記載の方法。
- 前記体腔内に送達される前記第1の親油性薬剤の濃度は治療有効量である、請求項1に記載の方法。
- 前記第1の親油性薬剤と組み合わせた前記第2の親油性薬剤の濃度は、治療有効量で前記体腔内に送達される、請求項11に記載の方法。
- 前記第1の親油性薬剤は、ゾタロリムスである、請求項1に記載の方法。
- 少なくとも1つの有益薬剤をさらに備える、請求項1に記載の方法。
- 前記第1の親油性薬剤は、20,000Pを超える分配係数を含む、請求項1に記載の方法。
- 前記第1の親油性薬剤は20,000Pを超える分配係数を含み、前記親油性薬剤は約30μg/ml未満の溶解度を有する、請求項1に記載の方法。
- 前記第1の親油性薬剤は少なくとも約4.3のLogPを含む、請求項1に記載の方法。
- 少なくとも約15μg/mLの溶解度を有する第1の親油性薬剤を備える、請求項1に記載の方法。
- 少なくとも約10,000(μg/mL)−1の移動係数を有する第1の親油性薬剤を備える、請求項1に記載の方法。
- 少なくとも約15,000(μg/mL)−1の移動係数を有する第1の親油性薬剤を備える、請求項1に記載の方法。
- 前記第1の親油性薬剤を前記体腔内に送達する投薬量は、最大約5日の期間にわたって約15μg/gから約150μg/gまでの範囲である、請求項1に記載の方法。
- 前記第1の親油性薬剤を前記体腔内に送達する投薬量は、約5日から最大約15日までの期間にわたって約15μg/gから約80μg/gまでの範囲である、請求項1に記載の方法。
- 前記第1の親油性薬剤を前記体腔内に送達する投薬量は、15日から最大約28日までの期間にわたって約5μg/gから約60μg/gまでの範囲である、請求項1に記載の方法。
- 前記第1の親油性薬剤は、遠位の心筋、ステント留置されていない心筋、下部の心筋、ステント留置されていない冠状動脈、及び遠位の冠状動脈のうちの少なくとも1つを含む、前記対象の標的領域において治療上有意な濃度に到達し、28日間全体を通してそれらの濃度を維持する、請求項1に記載の方法。
- 前記医療デバイスは対象体内に永久的又は一時的に埋め込まれる、請求項1に記載の方法。
- 前記第1の親油性薬剤は非晶質の形である、請求項1に記載の方法。
- 抗血栓剤、抗凝血剤、抗血小板薬、抗脂肪剤、血栓溶解剤、抗増殖剤、抗炎症薬、過形成を阻害する薬剤、平滑筋細胞阻害剤、抗生物質、成長因子阻害剤、細胞接着阻害剤、細胞接着促進剤、抗有糸分裂薬、抗フィブリン剤、抗酸化薬、抗悪性腫瘍薬、内皮細胞回復を促進する薬剤、マトリックスメタロプロテイナーゼ阻害剤、抗悪性腫瘍薬、代謝拮抗物質、抗アレルギー物質、ウイルスベクター、核酸、モノクローナル抗体、チロシンキナーゼの阻害剤、アンチセンス化合物、オリゴヌクレオチド、細胞透過促進剤、及びこれらの任意の組合せのうちの少なくとも1つを含む有益薬剤をさらに備える、請求項1に記載の方法。
- 血糖降下薬、脂質低下薬、タンパク質、核酸、赤血球生成促進に有用な薬剤、血管形成剤、抗潰瘍/逆流防止剤、及び制嘔吐剤/制吐薬、PPAR−アルファ作動薬、及びこれらの任意の組合せのうちの少なくとも1つを含む有益薬剤をさらに備える、請求項1に記載の方法。
- ナトリウムヘパリン、LMWヘパリン、ヘパリン様物質、ヒルジン、アルガトロバン、フォルスコリン、ヴァプリプロスト、プロスタサイクリン及びプロスタサイクリン類似体、デキストラン、D−phe−pro−arg−クロロメチルケトン(合成抗トロンビン剤)、糖タンパク質Iib/Iia(血小板細胞膜受容体拮抗薬抗体)、組換え型ヒルジン、トロンビン阻害剤、インドメタシン、サリチル酸フェニル、β−エストラジオール、ビンブラスチン、ABT−627(アトラセンタン)、テストステロン、プロゲステロン、パクリタキセル、メトトレキサート、ホテムスチン、RPR−101511A、シクロスポリンA、ビンクリスチン、カルベジオール、ビンデシン、ジピリダモール、メトトレキサート、葉酸、トロンボスポンジン模倣剤、エストラジオール、デキサメタゾン、メトリザミド、イオパミドール、イオヘキソール、イオプロミド、イオビトリドール、イオメプロール、イオペントール、イオベルソール、イオキシラン、イオジキサノール、イオトロラン、及びこれらのプロドラッグ、類似体、誘導体、及びこれらの任意の組合せのうちの少なくとも1つを含む有益薬剤をさらに備える、請求項1に記載の方法。
- 前記医療デバイスは血管内医療デバイスである、請求項1に記載の方法。
- 前記医療デバイスは、対象の血管系内で使用されるステント、薬物送達カテーテル、グラフト、及び薬物送達バルーンからなる群から選択された冠動脈内医療デバイスを含む、請求項1に記載の方法。
- 前記医療デバイスは、末梢血管ステント、末梢血管冠状動脈ステント、分解可能冠状動脈ステント、分解不可能冠状動脈ステント、自己拡張ステント、バルーン拡張ステント、及び食道ステントからなる群から選択されるステントを備える、請求項1に記載の方法。
- 前記医療デバイスは、動静脈グラフト、バイパスグラフト、ペニス整形、血管移植及びグラフト、静脈内カテーテル、小口径グラフト、人工肺カテーテル、電気生理学カテーテル、骨ピン、縫合糸アンカー、血圧及びステントグラフトカテーテル、豊胸手術、良性前立腺過形成及び前立腺癌インプラント、骨修復/強化デバイス、豊胸手術、整形外科用関節インプラント、人工歯根、埋め込まれた薬物注入管、腫瘍インプラント、疼痛処理インプラント、神経学的カテーテル、中心静脈アクセスカテーテル、カテーテルカフ、血管アクセスカテーテル、泌尿器カテーテル/インプラント、アテローム切除カテーテル、凝血塊採取カテーテル、PTAカテーテル、PTCAカテーテル、探り針(血管及び非血管)、薬物注入カテーテル、血管造影用カテーテル、血液透析カテーテル、神経血管バルーンカテーテル、胸腔吸引ドレナージカテーテル、電気生理学カテーテル、脳卒中治療カテーテル、膿瘍ドレナージカテーテル、胆道ドレナージ製品、透析カテーテル、中心静脈アクセスカテーテル、及び非経口(parental)フィーディングカテーテルからなる群から選択される、請求項1に記載の方法。
- 前記医療デバイスは、ペースメーカー、血管グラフト、括約筋デバイス、尿道デバイス、膀胱デバイス、腎臓デバイス、胃腸及び吻合デバイス、椎間板、止血用障壁、留め具、外科用ステープル/縫合糸/ネジ/プレート/ワイヤ/クリップ、グルコースセンサー、血液酸素付加デバイス配管、血液酸素付加デバイス膜、血液バッグ、バースコントロール/IUD及び関連する妊娠調節デバイス、軟骨修復デバイス、整形外科骨折修復、組織接着剤、組織シーラント、組織用足場、髄液短絡術、歯科骨折修復デバイス、硝子体内薬物送達デバイス、神経再生導管、電気刺激用リード、脊椎/整形外科修復デバイス、創傷被覆材、塞栓保護フィルタ、腹部大動脈瘤グラフト及びデバイス、神経動脈瘤治療コイル、血液透析デバイス、子宮出血パッチ、吻合閉鎖、体外診断薬、動脈瘤除外デバイス、神経パッチ、大静脈フィルタ、泌尿器拡張器、内視鏡外科及び創傷排液、外科組織抽出デバイス、遷移シース及び拡張器、冠状動脈及び末梢血管ガイドワイヤ、循環支援システム、中耳腔換気用チューブ、髄液短絡術、除細動器リード、経皮的閉鎖デバイス、ドレナージ管、気管支、血管コイル、血管保護デバイス、血管フィルタ及び遠位支持デバイスを含む血管インターベンションデバイス、塞栓フィルタ/封じ込め補助デバイス、AVアクセスグラフト、外科用タンポン、薬物送達カプセル、並びに心臓弁からなる群から選択される、請求項1に記載の方法。
- 前記医療デバイスは、心房中隔欠損症閉鎖、心調律管理用の電気刺激リード、組織及び機械人工心臓弁及びリング、動静脈シャント、弁輪形成デバイス、僧帽弁修復デバイス、左心室補助デバイス、左心耳フィルタ、心臓センサ、ペースメーカー電極、及びリードからなる群から選択される、請求項1に記載の方法。
- 心外膜及び/又は心膜嚢に送達される前記親油性薬剤の送達は連続的である、請求項6に記載の方法。
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Application Number | Priority Date | Filing Date | Title |
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US11/386,498 | 2006-03-22 | ||
US11/386,498 US8257725B2 (en) | 1997-09-26 | 2006-03-22 | Delivery of highly lipophilic agents via medical devices |
PCT/US2007/007255 WO2007112006A2 (en) | 2006-03-22 | 2007-03-22 | Delivery of highly lipophilic agents via medical devices |
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Also Published As
Publication number | Publication date |
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EP2004251A2 (en) | 2008-12-24 |
WO2007112006A3 (en) | 2008-06-12 |
US20060228453A1 (en) | 2006-10-12 |
US8257725B2 (en) | 2012-09-04 |
WO2007112006A2 (en) | 2007-10-04 |
JP5271892B2 (ja) | 2013-08-21 |
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