JP4768736B2 - 多重使用のための本質的に放射線不透過性の生体吸収性ポリマー - Google Patents
多重使用のための本質的に放射線不透過性の生体吸収性ポリマー Download PDFInfo
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Description
関連出願の相互参照
本出願は、2004年8月13日に出願した米国仮出願第60/601526号のU.S.C.§119(e)に基づく利益を主張するものである。
金属またはポリマーを含む医療用デバイスは、毎日多数の臨床応用のために使用されている。金属の医療用デバイスは、その材料の性質により一般に放射線不透過性であるのに対し、ポリマーの医療用デバイスは、そのままでは一般に放射線不透過性ではない。したがって、さまざまな医療処置に対する放射線不透過性の利点を提供するデバイスに使用するための生体吸収性の付加されたポリマー配合物の必要性が存在し続けている。上記デバイスの主要例としては、以下で説明する血管ステントが挙げられる。
[発明の概要]
本発明を要約するために、本発明のいくつかの態様、利点および新規な特徴を本明細書でこれまでに記述した。もちろん、必ずしもすべてのそのような利点が本発明のどれか特定の実施形態によって達成できるものではないことは当然である。したがって、本発明は、本明細書において教示もしくは示唆され得るその他の利点を必ずしも達成することなく、いわば本明細書において教示または示唆される1つの利点または1群の利点を達成または最適化する形で具現化または実施することができる。
X1およびX2は、BrおよびIからなる群からそれぞれ独立に選択され;
y1およびy2は、y1とy2の和が少なくとも1であることを条件としてそれぞれ独立にゼロまたは1から4の範囲の整数であり;
R1は、
R13およびR14は、−CH=CH−、−(CH2)c−、−(CHJ1)−、−CHJ2−CHJ3−、−CH=CH−(CHJ1)−および−(CH2)c−(CHJ1)−からなる群からそれぞれ独立に選択され;
cは、ゼロまたは1から8の範囲の整数であり;
J1、J2およびJ3は、H、Br、I、−NH−Q2および−C(=Z8)−OQ3からなる群からそれぞれ独立に選択され;
Q1、Q2およびQ3は、それぞれ独立に、Hまたは約1個から約30個の炭素原子を有する非結晶性基であり;
Z7およびZ8は、それぞれ独立にOまたはSであり;
A1は、
R5は、H、C1〜C30アルキル、およびC1〜C30ヘテロアルキルからなる群から選択される)
を有する。好ましい実施形態において、X1、X2、y1およびy2は、X1、X2が、ポリマーを放射線不透過性にするために有効である量で存在するように選択する。
Z1およびZ2は、それぞれ独立にOまたはSであり;
mは、1から8の範囲の整数である)
である。
Z1およびZ2は、それぞれ独立にOまたはSであり;
jおよびmは、それぞれ独立に1から8の範囲の整数である)
である。
Z1、Z2およびZ3は、それぞれ独立にOまたはSであり;
jおよびmは、それぞれ独立に1から8の範囲の整数である)
である。
Bは、−O−(CHR6)p−O)q−であり;
R6は、HまたはC1からC3のアルキルであり;
pおよびqは、それぞれ個々に、約1から約100の範囲の整数であり;
A2は、
R7は、HまたはC1からC30の炭化水素であり;R11は、C1〜C30アルキル、C1〜C30ヘテロアルキル、C5〜C30アリール、C6〜C30アルキルアリール、およびC2〜C30ヘテロアリールからなる群から選択される)
を含む。別の実施形態は、上記ポリマーを含む医療用デバイスを提供する。一実施形態において、Bは、脂肪族線状または枝分かれのジオールまたはポリ(アルキレングリコール)単位である。
X3およびX4は、BrおよびIからなる群からそれぞれ独立に選択され;
y3およびy4は、それぞれ独立にゼロまたは1から4の範囲の整数であり;
R2は、
R8およびR9は、それぞれ独立にHまたは非結晶性C1からC30の炭化水素であり;
Z4、Z5およびZ6は、それぞれ独立にOまたはSであり;
aおよびbは、それぞれ独立に1から8の範囲の整数であり;
A3は、
式中、R10は、H、C1〜C30アルキル、およびC1〜C30ヘテロアルキルからなる群から選択され;式中、R12は、C1〜C30アルキル、C1〜C30ヘテロアルキル、C5〜C30アリール、C6〜C30アルキルアリール、およびC2〜C30ヘテロアリールからなる群から選択される)を含む。別の実施形態は、上記ポリマーを含む医療用デバイスを提供する。
[図面の簡単な説明]
図1は、ステントが1方向の拡大を示すことできるように下向きに屈折する屈折性の歯を有する本発明の1つの好ましい実施形態によるスライド固着ステント構造の詳細図である。
[好ましい実施形態の詳細な説明]
生体吸収性放射線不透過性ステントの開発に関する重要な必要性を満たすために、本発明者らは、式(I)の繰返し単位を有するいくつかのポリマー材料を開発した。式(I)の繰返し単位を有する好ましいポリマーは、ジカルボン酸、デスアミノチロシル−チロシンのハロゲン化(例えば、ヨウ素化または臭素化)誘導体およびポリ(アルキレングリコール)から選択される構造単位の誘導体の組合せを含み、それはステントを含む医療用デバイスの製作におけるそれらの使用と調和した望ましい物理機械的および物理化学的特性を示す。例えば、本発明の好ましい実施形態によって表現されるステントは、(a)従来のX線透視法によって見ることができるために十分に放射線不透過性であり;(b)動脈または周辺組織内のラジアル加圧の医学的に相応するレベルに対応する十分な強度のものであり;かつ/または(c)異なる長さの時間のまたは治療薬の溶離のためのステントの存在を必要とする一連の応用の必要性を解決するように調節することができる望ましい再吸収特性を有する。
X1およびZ2は、BrおよびIからなる群からそれぞれ独立に選択され;
y1およびy2は、y1とy2の和が少なくとも1であることを条件としてそれぞれ独立にゼロまたは1から4の範囲の整数であり;
R1は、
R13およびR14は、−CH=CH−、−(CH2)c−、−(CHJ1)−、−CHJ2−CHJ3−、−CH=CH−(CHJ1)−および−(CH2)c−(CHJ1)−からなる群からそれぞれ独立に選択され;
cは、ゼロまたは1から8の範囲の整数であり;
J1、J2およびJ3は、H、Br、I、−NH−Q2および−C(=Z8)−OQ3からなる群からそれぞれ独立に選択され;
Q1、Q2およびQ3は、それぞれ独立に、Hまたは約1個から約30個の炭素原子を有する非結晶性基であり;
Z7およびZ8は、それぞれ独立にOまたはSであり;
A1は、
R5は、H、C1〜C30アルキル、およびC1〜C30ヘテロアルキルからなる群から選択される)
を有する。好ましい実施形態において、X1、X2、y1およびy2は、X1、X2が、ポリマーを放射線不透過性にするために有効である量で存在するように選択される。
Z1、Z2およびZ3は、それぞれ独立にOまたはSであり;
jおよびmは、それぞれ独立に1から8の範囲の整数である)
からなる群から選択される。
Bは、−O−(CHR6)p−O)q−であり;
R6は、HまたはC1からC3のアルキルであり;
pおよびqは、それぞれ個々に、約1から約100の範囲の整数であり;
A2は、
ここでR7は、HまたはC1からC30の炭化水素であり、R11は、C1〜C30アルキル、C1〜C30ヘテロアルキル、C5〜C30アリール、C6〜C30アルキルアリール、およびC2〜C30ヘテロアリールからなる群から選択される)
を有する。別の実施形態は、上記ポリマーを含む医療用デバイスを提供する。一実施形態において、Bは、脂肪族線状または枝分かれジオールまたはポリ(アルキレングリコール)単位である。
X3およびX4は、BrおよびIからなる群からそれぞれ独立に選択され;
y3およびy4は、それぞれ独立にゼロまたは1から4の範囲の整数であり;
R2は、
R8およびR9は、それぞれ独立にHまたは非結晶性C1からC30の炭化水素であり;
Z4、Z5およびZ6は、それぞれ独立にOまたはSであり;
aおよびbは、それぞれ独立に1から8の範囲の整数であり;
A3は、
ここで、R10は、H、C1〜C30アルキル、およびC1〜C30ヘテロアルキルからなる群から選択され;ここでR12は、C1〜C30アルキル、C1〜C30ヘテロアルキル、C5〜C30アリール、C6〜C30アルキルアリール、およびC2〜C30ヘテロアリールからなる群から選択される)
をさらに有する。別の実施形態は、上記ポリマーを含む医療用デバイスを提供する。
yl、y2、y3、y4は、それぞれ独立に0、1、2、3または4であり;
ここでfおよびgは、fとgの和が1未満であることを条件として0から1の範囲であり得;
ここでR1およびR2独立に:
ここでR3およびR4は、それぞれ独立にHまたは非結晶性C1からC30の炭化水素であり;
ここでjおよびmは、独立に1から8の整数であり;
ここでZl、Z2およびZ3は、それぞれ独立にOまたはSであり;
ここでAlは:
ここでR5は、HまたはC1からC30の炭化水素であり;
ここでA2およびA3は、それぞれ独立に
ここでR7は、HまたはC1からC30の炭化水素であり、R11は、C1〜C30アルキル、C1〜C30ヘテロアルキル、C5〜C30アリール、C6〜C30アルキルアリール、およびC2〜C30ヘテロアリールからなる群から選択され;
ここでBは、−O−(CHR6)p−O)q−であり;
ここでR6は、HまたはC1からC3のアルキルであり;
pおよびqは、それぞれ個々に、約1から約100の範囲の整数である)
を有する。
合成スキーム1
合成スキーム4
合成スキーム6
・放射線不透過性は、クリニックで用いられる標準法であるX線透視法によるヒト胸部の背景に対するステント構造の視感度を確保するために十分であることが望ましい。
・本発明の態様によるステントは、低い交差プロフィールを提供するためおよび優れた長さ方向の柔軟性を与えるための壁が形成されていることが好ましい。好ましい実施形態においてその壁の厚さは、約0.0001インチから約0.0250インチ、より好ましくは約0.0010から約0.0100インチである。しかしながら、壁の厚さは少なくとも一部は選択した材料による。例えば、厚さは、プラスチックおよび分解可能な材料については約0.0060インチ未満であり得、金属材料については約0.0020インチ未満であり得る。より詳しくは、3.00mmのステント適用に対しては、プラスチック材料を使用する場合、厚さは、好ましくは約0.0040インチから約0.0045インチの範囲である。しかしながら、さまざまな直径を有するステントは、胆管およびその他の末梢血管への適用に対して異なる厚さを採用することができる。上の厚さ範囲は、組立ておよび展開を含むデバイスのすべての態様を通した好ましい特徴を提供することが見出されている。しかしながら、上記の厚さ範囲が、本発明の範囲に関して限定しているはずはなく、本発明の教示が、本明細書で述べていない寸法を有するデバイスにも適用できることは当然である。
・ステントは、急性血栓症を防ぐために、好ましくは血液適合性である。したがって、デバイスの表面は、タンパク質吸着および血小板/単球付着に好ましくは耐性を示す。さらに、該デバイス表面は、理想的には内皮過成長には有利に働くが平滑筋細胞の付着および成長(これは再狭窄を引き起こすことに関わる)は阻止する。
・ステントは、それらの機械的強度(例えば、フープ強度)を、好ましくは約1〜24カ月、より好ましくは約3〜18カ月、さらにより好ましくは約3〜12カ月、最も好ましくは約3〜6カ月の期間にわたって維持する。
・ステントは、そのステントが、しばらく経って、血管のほぼ同じ領域を再治療するためまたは血管バイパス等のその他の形態の血管の再処置を可能にするために、生体吸収性または金属あるいはその他の任意のステントを使用することができるように、ステントが一定期間体内腔中に留置されるような望ましい生体内分解および生体吸収のプロフィールを有することが好ましい。
ステント設計
本明細書に記載の本発明の好ましい実施形態は、一般に、体内腔の支えを維持するために膨らますことができる医療用インプラントに関する。長年にわたって、広範なステントのタイプが提案されている。ステントの構造は、かなり異なり得るが、ほとんどすべてのステントは小さい直径を有する押しつぶされた状態から大きな直径を有する拡大した状態に膨らますことができるように構成されている。押しつぶされた状態の間にステントは通常はカテーテルにより血管またはその他の体内腔を通して治療部位に送達する。治療部位に到達した後、ステントは、血管壁を支えるために放射状に移植できる大きさまで膨らませる。ステントの押しつぶされた状態から膨らんだ状態までの拡大は、さまざまな異なる方法で達成することができる。さまざまなタイプのステントが、それらの構造および拡大の方式に基づいて以下に記載されている。さらなる情報について、さまざまなステントのタイプが、Balconらによる“Recommendations on Stent Manufacture,Implantation and Utilization,”European Heart Journal(1997),vol.18,pages 1536−1547に、およびPhillipsらによる“The Stenter’s Notebook,”Physician’s Press(1998),Birmingham,Michiganに記載されており、それらの開示は、参照により全体として本明細書に組み込まれている。
治療薬を送達するステント
治療薬は、生体吸収性ステントに組み込み、かつ/またはそのステント表面の少なくとも一部分にコートすることによって該薬剤の局所放出を提供することができる。好ましい実施形態において、治療薬は、ポリマーとブレンドするかまたは当業者には知られているその他の方法によって混合されてステント内に包含される。ステントの他の好ましい実施形態においては、治療薬は、ステント表面のポリマーコーティングから送達される。別の好ましい変形形態においては、治療薬は、ポリマーコーティングではない手段により送達される。ステントの他の好ましい実施形態においては、治療薬は、ステントの少なくとも1つの領域または1つの表面から送達される。
(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸チロシンエチルエステル)の合成
3−(4−ヒドロキシフェニル)プロパン酸のヨウ素化
溶液(a)の調製:250mLの三角フラスコに100mLの蒸留水、24gのヨウ化カリウム、および25gのヨウ素を加える。その混合物をすべての固体が溶解するまで一晩撹拌する。
ステップ2:(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸チロシンエチルエステル)の調製
250mLの上部撹拌器を装着した3つ口丸底フラスコに、17.0g(0.0582モル)の3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸、12.25g(0.0585モル)のチロシンエチルエステル、および25mLのN−メチル−2−ピロリドン(NMP)を加える。その混合物を透明な溶液が得られるまで撹拌する。そのフラスコを氷入りのウォーターバス中で冷却し、次いで、11.84g(0.0619モル)の1−(3−ジメチルアミノプロピル)−3−エチルカルボジイミドヒドロクロリド(EDCI HCl)を1回で加え、続いて15mLのNMPを加える。冷却バスを2.5時間後に除去し、反応はそのまま室温で一晩継続する。71mLの酢酸エチルを加え、撹拌をさらに15分間維持する。粗生成物を次に500mLの分液濾斗に移し、75mLのブラインで1回、次いで3%NaHCO3/14%NaClの2個のアリコート(75mLおよび35mL)で、続いて0.4MのHCl/14%NaClのアリコート35mLで抽出し、最後にブラインで抽出する。有機相を硫酸マグネシウムにより乾燥し、活性炭で処理し、濾過して濃厚なシロップ状になるまで濃縮すると、それは数時間後に結晶化して固体物質となる。その生成物を、機械的撹拌を用いて塩化メチレン中で粉末状とし、次いでそれを濾過して回収し、窒素気流下で、続いて高真空により乾燥する。
(3−(3−ヨード−4−ヒドロキシフェニル)−2−プロペン酸チロシンエチルエステルの合成
(3−(4−ヒドロキシフェニル)−2−プロペン酸のヨウ素化
溶液(a)の調製:250mLの三角フラスコに100mLの蒸留水、24gのヨウ化カリウム、および25gのヨウ素を加えることができる。その混合物をすべての固体が溶解するまで一晩撹拌することができる。
ステップ2:(3−(3−ヨード−4−ヒドロキシフェニル)−2−プロペン酸チロシンエチルエステル)の調製
250mLの上部撹拌器を装着した3つ口丸底フラスコに、17.0gの3−(3−ヨード−4−ヒドロキシフェニル)−2−プロペン酸、12.25g(0.0585モル)のチロシンエチルエステル、および25mLのNMPを加えることができる。その混合物を透明な溶液が得られるまで撹拌することができる。そのフラスコを氷入りのウォーターバス中で冷却することができ、次いで、11.84g(0.0619モル)のEDCI HClを1回で加え、続いて15mLのNMPを加えることができる。冷却バスを2.5時間後に除去することができ、反応はそのまま室温で一晩継続することができる。71mLの酢酸エチルを加えることができ、撹拌をさらに15分間維持することができる。粗生成物を次に500mLの分液濾斗に移し、75mLのブラインで1回、次いで3%NaHCO3/14%NaClの2個のアリコート(75mLおよび35mL)で、続いて0.4MのHCl/14%NaClのアリコート35mLで抽出し、最後にブラインで抽出することができる。有機相を硫酸マグネシウムにより乾燥し、活性炭で処理し、濾過して濃厚なシロップ状になるまで濃縮することができ、それは数時間後に結晶化して固体物質となり得る。その生成物は、機械的撹拌を用いて塩化メチレン中で粉末状とし、次いでそれを濾過して回収し、窒素気流下で、続いて高真空により乾燥することができる。
(2−(3−ヨード−4−ヒドロキシベンジル)メチルマロネートチロシンエチルエステル)の合成
2−(4−ヒドロキシベンジル)メチルマロネートのヨウ素化
溶液(a)の調製:250mLの三角フラスコに100mLの蒸留水、24gのヨウ化カリウム、および25gのヨウ素を加えることができる。その混合物をすべての固体が溶解するまで一晩撹拌することができる。
ステップ2:(2−(3−ヨード−4−ヒドロキシベンジル)メチルマロネートチロシンエチルエステル)の調製
250mLの上部撹拌器を装着した3つ口丸底フラスコに、23gの2−(3−ヨード−4−ヒドロキシベンジル)メチルマロネート、12.25g(0.0585モル)のチロシンエチルエステル、および25mLのNMPを加えることができる。その混合物を透明な溶液が得られるまで撹拌することができる。そのフラスコを氷入りのウォーターバス中で冷却することができ、次いで、11.84g(0.0619モル)のEDCI HClを1回で加え、続いて15mLのNMPを加えることができる。冷却バスを2.5時間後に除去することができ、反応はそのまま室温で一晩継続することができる。71mLの酢酸エチルを加えることができ、撹拌をさらに15分間維持することができる。粗生成物を次に500mLの分液濾斗に移し、75mLのブラインで1回、次いで3%NaHCO3/14%NaClの2個のアリコート(75mLおよび35mL)、次いで0.4MのHCl/14%NaClの35mLのアリコート、最後にブラインで抽出することができる。有機相を硫酸マグネシウムにより乾燥し、活性炭で処理し、濾過して濃厚なシロップ状になるまで濃縮することができ、それは数時間後に結晶化して固体物質とすることができる。その生成物は、機械的撹拌を用いて塩化メチレン中で粉末状とし、次いでそれを濾過して回収し、窒素気流下で、続いて高真空により乾燥することができる。
EOPとの溶液重合によるポリ(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸−チロシンエチルエステル)
アルゴン気流下、5.5gの(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸−チロシンエチルエステル)、5.07gの4−ジメチルアミノピリジン(DMAP)、および50mlの塩化メチレンを、濾斗を備えた250mlのフラスコに移す。3.07gのエチルホスホジクロリデート(EOP)の30mlの塩化メチレン中の溶液を濾斗に加える。フラスコ中の溶液を撹拌しながら−40℃に冷却し、EOP溶液を濾斗から滴下して加える。添加が完了したら、その混合物の温度を45℃に徐々に上昇させ、還流温度で一晩維持する。
EOPとの重合によるポリ(3−(3−ヨード−4−ヒドロキシフェニル)−2−プロペン酸チロシンエチルエステル)
アルゴン気流下、5.5gの(3−(3−ヨード−4−ヒドロキシフェニル)−2−プロペン酸−チロシンエチルエステル)、5.07gの4−ジメチルアミノピリジン(DMAP)、および50mlの塩化メチレンを、濾斗を備えた250mlのフラスコに移す。3.07gのエチルホスホジクロリデート(EOP)の30mlの塩化メチレン中の溶液を濾斗に加える。フラスコ中の溶液を撹拌しながら−40℃に冷却し、EOP溶液を濾斗から滴下して加える。添加が完了したら、その混合物の温度を45℃に徐々に上昇させ、還流温度で一晩維持する。
EOPとの重合によるポリ(2−(3−ヨード−4−ヒドロキシベンジル)メチルマロネート−チロシンエチルエステル)
アルゴン気流下、7.8gの(2−(3−ヨード−4−ヒドロキシベンジル−)メチルマロネート−チロシンエチルエステル)、5.07gの4−ジメチルアミノピリジン(DMAP)、および50mlの塩化メチレンを、濾斗を備えた250mlのフラスコに移す。3.07gのエチルホスホジクロリデート(EOP)の30mlの塩化メチレン中の溶液を濾斗に加える。フラスコ中の溶液を撹拌しながら−40℃に冷却し、EOP溶液を濾斗から滴下して加える。添加が完了したら、その混合物の温度を45℃に徐々に上昇させ、還流温度で一晩維持する。
CNBRとの溶液重合によるポリ(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸−チロシンエチルエステル)
(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸−チロシンエチルエステル)ジシアネートの重合
(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸−チロシンエチルエステル)と(3−(3−ヨード−4−ヒドロキシフェニル)プロパン酸−チロシンエチルエステル)ジシアネートとの正確に化学量論量の混合物の44%(w/v)THF溶液を用意し、続いて1.0モルパーセントの溶液濃度を得るために十分な1Mのカリウムt−ブトキシドを添加する。その混合物を23℃で撹拌し、ジシアネートの転化を分光光度法で監視する。溶媒を蒸発させることにより粗生成物を得る。その生成物を過剰のアセトンで注意深く洗浄し真空中で乾燥させる。
Claims (29)
- 本質的に放射線不透過性、生体適合性、生体吸収性のポリマーであって、1つまたは複数の式(I)の繰返し単位:
X1およびX2は、BrおよびIからなる群からそれぞれ独立に選択され;
y1およびy2は、y1とy2の和が少なくとも1であることを条件としてそれぞれ独立にゼロまたは1から4の範囲の整数であり;
R1は、
R13およびR14は、−CH=CH−、−(CH2)c−、−(CHJ1)−、−CHJ2−CHJ3−、−CH=CH−(CHJ1)−および−(CH2)c−(CHJ1)−からなる群からそれぞれ独立に選択され;
cは、ゼロまたは1から8の範囲の整数であり;
J1、J2およびJ3は、H、Br、I、−NH−Q2および−C(=Z8)−OQ3からなる群からそれぞれ独立に選択され;
Q1、Q2およびQ3は、それぞれ独立に、Hまたは1個から30個の炭素を有する非結晶性基であり;
Z7およびZ8は、それぞれ独立にOまたはSであり;
A1は、
R5は、H、C1〜C30アルキル、およびC1〜C30ヘテロアルキルからなる群から選択される)
を含むポリマー。 - 請求項1に記載のポリマーを含む、医療デバイス。
- 血管系、筋骨格/整形系、神経系、呼吸器系、生殖器系、泌尿器系、消化器系、内分泌系、造血系、または外皮系から選択される領域に配置するために構成されている、請求項2に記載の医療デバイス。
- インビボで使用するために構成されている、請求項2に記載の医療デバイス。
- エクスビボで使用するために構成されている、請求項2に記載の医療デバイス。
- インビトロで使用するために構成されている、請求項5に記載の医療デバイス。
- 前記医療デバイスがステントを含む、請求項2に記載の医療デバイス。
- 前記ステントが、シートステント、編組みステント、自己拡張ステント、ワイヤーステント、変形可能ステント、およびスライド/固定ステントからなる群から選択される構造をさらに含む、請求項7に記載の医療デバイス。
- 前記ステントが、管状部材を形成するように配置された実質的に非変形性の少なくとも2つの要素を含み、該非変形性要素が、管状部材が崩壊した直径から拡張した直径に拡張することを可能にするためにスライド可能なように相互連結している、請求項7に記載の医療デバイス。
- 前記ステントが、スライド可能なようにかみ合った一連のラジアル要素および該ラジアル要素の一方向だけのスライドを可能にするように適応された固定構造を含む管状部材をさらに含み、前記管状部材が最初の崩壊した直径から第2の拡張した直径に最小の反動で拡張するように構成されている、請求項7に記載の医療デバイス。
- 有効量の治療薬をさらに含む、請求項2に記載の医療デバイス。
- 前記治療薬が、抗増殖性薬剤、抗炎症薬、抗基質メタロプロテイナーゼ剤、脂質降下薬、コレステロール改質剤、抗血栓剤、および抗血小板薬からなる群から選択される、請求項11に記載の医療デバイス。
- 前記有効量が、再狭窄の抑制、血栓症の抑制、プラーク形成の抑制、プラーク破裂の抑制、炎症の抑制、コレステロールの低下、および治癒促進からなる群から選択される効果を提供するために十分である、請求項11に記載の医療デバイス。
- X1およびX2がヨウ素である、請求項2に記載の医療デバイス。
- 非ハロゲン化コーティングをさらに含む、請求項2に記載の医療デバイス。
- 前記ポリマーが前記医療デバイスの少なくとも一部分にコーティングを形成している、請求項2に記載の医療デバイス。
- 請求項7に記載のステントおよび展開手段を有するカテーテルを含む血管内の部位を治療するためのシステムであって、前記カテーテルが、該ステントを前記部位に送達するように適合されており、前記展開手段が該ステントを展開するように適合されているシステム。
- 請求項18に記載のポリマーを含む医療デバイス。
- 1つまたは複数の式(Ia)の繰返し単位:
X3およびX4は、BrおよびIからなる群からそれぞれ独立に選択され;
y3およびy4は、それぞれ独立にゼロまたは1から4の範囲の整数であり;
R2は、
R8およびR9は、それぞれ独立にHまたは非結晶性C1からC30の炭化水素であり;
Z4、Z5およびZ6は、それぞれ独立にOまたはSであり;
aおよびbは、それぞれ独立に1から8の範囲の整数であり;
A3は、
R10は、H、C1〜C30アルキル、およびC1〜C30ヘテロアルキルからなる群から選択され;
R12は、C1〜C30アルキル、C1〜C30ヘテロアルキル、C5〜C30アリール、C6〜C30アルキルアリール、およびC2〜C30ヘテロアリールからなる群から選択される)
をさらに含む、請求項18に記載のポリマー。 - 請求項20に記載のポリマーを含む医療デバイス。
- 請求項22に記載のポリマーを含む医療デバイス。
- 請求項24に記載のポリマーを含む医療デバイス。
- 請求項26に記載のポリマーを含む医療デバイス。
- 有効量の放射線不透過性作用物質をさらに含む、請求項2に記載の医療デバイス。
- 有効量の磁気共鳴増強剤をさらに含む、請求項2に記載の医療デバイス。
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WO2006020616A1 (en) | 2006-02-23 |
US7473417B2 (en) | 2009-01-06 |
CA2577018C (en) | 2012-03-27 |
RU2007108783A (ru) | 2008-09-20 |
EP1778761A1 (en) | 2007-05-02 |
CA2577018A1 (en) | 2006-02-23 |
CN101014642B (zh) | 2010-04-21 |
AU2005272944A1 (en) | 2006-02-23 |
AU2005272944B2 (en) | 2009-01-15 |
US20060036316A1 (en) | 2006-02-16 |
EP1778761B1 (en) | 2021-09-29 |
JP2008510034A (ja) | 2008-04-03 |
CN101014642A (zh) | 2007-08-08 |
RU2396289C2 (ru) | 2010-08-10 |
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