CN1915188A - 可再定位和再获取的血管扩张/移植物 - Google Patents

可再定位和再获取的血管扩张/移植物 Download PDF

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CN1915188A
CN1915188A CNA2006101110165A CN200610111016A CN1915188A CN 1915188 A CN1915188 A CN 1915188A CN A2006101110165 A CNA2006101110165 A CN A2006101110165A CN 200610111016 A CN200610111016 A CN 200610111016A CN 1915188 A CN1915188 A CN 1915188A
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库尔特·安普拉茨
迈克尔·阿弗雷莫夫
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Abstract

一可收缩医疗装置以及将其植入选定的器官和血管的相关方法，其中，该医疗装置由形状记忆纤维制成。该装置较佳地由连续管状纤维织物和终结于一为贯穿通道而设的一开口端的各端组成。各终端还包括一附着于端部外围的固定体，其中，基本平面由其周边与纵向轴相交而形成至少一钝角或一锐角而确定。纤维织物可在注塑模中进行热处理以基本形成装置所希望的形状。固定部分也可附着在引导线末端或传送管上，由此可布置并在医疗装置布置后将其收回。

Description

可再定位和再获取的血管扩张/移植物
本申请是第2004100877024号中国发明专利申请的分案申请，该申请是2001年3月27日提交的申请号为01112410.5、名称为可再定位和再获取的血管扩张/移植物的中国发明专利申请的分案。
技术领域
本发明总体涉及一装置，以及用来治疗内腔的局部非正常胀大的一最小侵入过程，更具体地，本发明涉及一细小的、可用作非外科治疗在血管和内部器官内动脉瘤、痿管(fistular)、肿块团(legion)之类东西的合成移植物。按照本发明制成的装置可再回收的，并在装置端部具有间隔的标记，以使该装置能更好地定位。该装置特别适用于通过一导管之类的东西传送至病人静脉系统内或病人类似的内部血管或器官内的较远部分。
背景技术
今已在多种医疗过程中使用了多种扩张/移植物。例如，扩张/移植物(生化型及合成移植物)已用于治疗动脉瘤、痿管炎。典型地，扩张器是圆柱形的并可通过导管传送至病人体内一特定位置。导管可用于到达一血管系统中选定血管，该处要用到血管扩张器。在斯皮里基李尔兹(Spiridigliozzi)等人的第5,824,055号美国专利中，描述了一种扩张/移植物系统，其中移植物较佳地由聚酯纤维织物构成并可通过多种传统扩张器固定在位。尽管斯皮里基李尔兹等人认识到移植物再获取特性的必要性，它们仍仅描述一种可在部分布置后收回的移植物。因此，这里有必要提供一在完全布置后能收回的移植物。
当传送一移植物时，也需要在移植物完全布置后监控其方位、尽管已将可荧光检测的标志附着于扩张器上，在二维观察时，这些扩张器上的末端仍难以定向。罗姆巴蒂等人的第5,824,042号美国专利描述一在其上具有一位置标志的内淋巴修复物，然而，确定其末端旋转方向的的标志的使用未被描述。这样，需要有一种具有一可表示其回转方向的标志的扩张器，无论该装置是在两维或三维地观察。本发明阐述了这些和那些要求，这对精于此领域的人员通过对本发明描述的回顾将更为明显。
发明内容
由此本发明的目的是提供一再回收的、细小的、可自膨胀的扩张器。本发明装置较佳地由一连续管状纤维织物制成，该管状纤维织物具有一细小的松弛结构，并包括一夹子使装置可安装到传送装置末端和引导线上(可在装置布置后回收)。在较佳实施例中，该装置由具有多个交织金属线的金属纤维织物。该装置具有近端和末梢端，以及将金属纤维固定在各端的装置或夹子。该夹子可防止金属纤维织物松开。较佳实施例的结构具有一基本呈圆柱形的松弛结构，该结构包括一在两端部间的通道。不作为任何限制，本发明装置的特定形状特别适用于治疗血管中的动脉瘤。
在本发明一实施例中，装置由多条织线组成。装置具有近端和末梢端，各端具有装于其上的装置以将织线固定在一起，由此约束纤维使其不至松开，装置具有松弛的圆柱结构，其中，松弛的圆柱结构包括一穿过在装置各端之间中心部分的通道，装置端部分从装置的圆柱本体开始沿一定角度延伸，其中至少一端的平面与圆柱部分的纵向轴相交而形成至少一钝角或一锐角，该装置还具有一收缩结构，用来穿过一导管或通道而进入病人体内。
另外，装置的至少一端包括一沿末端周边彼此间隔一定距离的多个标志。同样，固定体安装于传送装置上。织线的倾角和纬纱数使金属网孔可天然地形成血栓而设定的，其中有血纤维蛋白形成于装置表面上。
在本发明另一实施例中，装置的末端张开，其中末端的宽度比装置的中间截面更大。在本发明又一实施例中，在装置的中间截面上形成有一凹孔，并可容纳本发明的另一装置的一端。在本发明又一实施例中，圆柱形本体可弯曲并包括一形成于本体弯曲处附近的凹孔。该实施例一第一移植物可拉伸并穿过该实施例中的第二移植物的凹孔中。当第一移植物恢复到松弛结构时，第一和第二移植物一起形成“Y”移植物。
当由弹性纤维织物形成这些血管内装置时，提供多根弹性线或弹性绳，通过编织弹性绳而形成纤维织物以产生弹性材料。弹性线绳具有记忆特性并较佳地由具有已知特定结构的非生物排斥性金属合金制成。移植物的一个或各个内外周边的所有部分均由非生物排斥性材料封装。不作为任何限制，该非生物排斥性材料可以包括一已知的、合适的纤维，该纤维由特拉华的戈尔公司制造。
在较佳实施例中，编织纤维织物一般符合注塑元件的注塑面的形状而变形，且编织纤维织物在一提高温度的热处理作用下和注塑元件的表面接触。热处理的时间和温度基本设定在使编织纤维处在变形状态时。热处理后，纤维从与之接触的注塑模中移走并基本维持变形形状。经如此处理的编织纤织物维确定医疗装置一松弛状态，在该状态下医疗装置穿过一导管进入病人身体内腔并可拉伸或膨胀并布置。精于本领域的人员应懂得注塑模的孔穴必须与装置所希望形成的形状一致。另外，注塑模还包括内核和/或凸轮以在装置各端充分形成所希望的开口。
使用时，将一引导管定位并伸入病人体内，由此导管末梢端靠近所需治疗处以治疗生理病症。本发明的具有一特定形状的医疗装置伸长并插入导管内腔。装置被推挤并穿透导管并穿出导管末梢，于是，由于装置具有保持预设形状的能力，它将基本回复至在治疗处附近的松弛状态。当装置完全布置时，医生或使用者可通过放射线照相技术、荧光技术或其它已知的非侵入式的、观察病人体内的装置位置的方法确定其是否已完全布置。然后将引导线或传送管从夹子上放开并移除。
附图说明
图1是本发明的可回收的、自膨胀的血管扩张/移植物的立体图；
图2是图1所示类型的扩张/移植物的后侧视图；
图3是图1所示类型的扩张/移植物的前侧视图；
图4是图1所示类型的扩张/移植物的端部视图；
图5是图1所示类型的扩张/移植物的俯视图；
图6是图1所示类型的扩张/移植物的仰视图；
图7是本发明另一实施例的侧视图；
图8是本发明又一实施例的侧视图；
图9是图8所示类型的装置的俯视图；
图10是本发明又一实施例的侧视图；
图11表示图10所示装置从图8和图9所示类型的装置的孔中延伸出来；
图12是本发明另一实施例的前视图；
图13是图12所示类型的装置的后视图；以及
图14表示图12所示类型的第一装置部分地从图12所示类型的第二装置延伸的前视图。
具体实施方式
下面结合所附权利要求和附图对本发明较佳实施例进行描述，其相同的标号中在各个视图中表示相同的部件。本发明广泛地表示了自膨胀式血管扩张/移植装置的可应用改善。详细的实施例在这里旨在作为包括于本发明但不是用来限制本发明改善的示例或补充。
本发明提供一特别适用于治疗动脉瘤的由经皮肤导管定向的自膨胀式可回收扩张/移植物10。扩张移植物10包括一管状的基本呈圆柱形的本体部分12以及一倾斜的末端部分14和16。圆柱部分12包括一在末端16和14之间延伸的通道18。斯藤特移植物10较佳地由包括多个金属交织线的管状金属织物制成。一夹子24装于金属织物的外端，由此抑制金属织物的松开。夹子24中的至少一个可与引导线或导管配合，以将其传递到病人体内的预定位置。
管状“织物”由多个具有预定的相对方向的线绳。精于此领域的人员会懂得织物线的倾角和纬纱数可以在满足所述织物的密度要求的前提下变化。管状纤维织物具有界定两套本质上平行的、螺旋堆叠的金属线，两金属线中的一条具有一“指向”，即一相反于另一金属线的旋转方向。这种管状纤维在纺织行业中称为管状编织物。
线绳的倾角(即，在旋转线和织物的轴之间所确定的角度)以及纤维的纬纱数(即，在单位长度上的旋转圈数)和其它一些因素，例如应用于管状织物的线数、各织物线的直径尺寸以及织物直径都是决定装置多个重要特性的重要因素。例如织物的纬纱数和倾角越大，由此在纤维中线的密度约大，装置将更坚挺。另外，各织物线的直径越大装置更坚梃。更大的线密度也将提供装置一更大的线表面积，这一般会具有改善形成于装置纤维蛋白的趋势。这种形成血栓将通过在其上覆盖溶血栓物而改善，或通过在其上覆盖光滑的、抗血栓的合成物而减少。当使用一管状织物而形成本发明装置时，直径大约4mm的管状织物具有大约72根织物线可制造一扩张/植入装置。当然，精于此领域的人员会懂得织物线的数量可增加并实际上可超过144根，且其直径也可按照移植物定位处的血管尺寸增加或减少。
管状金属纤维线绳较佳地由所述形状记忆合金制成，装置也可由形状记忆合金制造而成，其中，装置形状可依赖于温度或独立于温度制造而成。当制造该装置的形状记忆合金独立于温度的改变时，可通过将材料加热至某一相变温度之上以使材料产生一相位变化而固定一较佳的结构。当合金冷却后，合金将“记住”其在热处理时的形状并可确定低于热处理温度的独立结构，除非将合金约束而使其不这样。
无任何限制意图，适合的线绳材料将包括一钴基的低热膨胀的合金，在业内称其为埃尔格合金(ELGELOY)，镍基高温高强度的“超级合金”(包括镍钛诺)，从商业上可通过，例如“海恩斯国际”的商业牌号为哈斯特罗伊(HASTELLOY)、通过“国际镍”公司的名义出售镍基热处理合金、或多种级别的不锈钢获得。选择线绳的合适材料的重要因素是线绳可保持由注塑面(下面将提到)受特定热处理作用时产生的变形量。
在较佳实施例中，线绳由一形状记忆合金，NiTi(镍钛诺)，即接近化学计量的镍钛合金并包括微量的其它金属成份的合金以达到所需要的特性。处理要素和NiTi合金的成份变化已知于现有技术，因此无需在此讨论这样的合金。在美国第5067489号(林德)和4991602号(安普拉兹)专利中包含有这方面的教程以待参阅，其中讨论在引导线中的形状记忆合金NiTi的使用。这种NiTi合金至少就部分而言是较佳的，因为它们可经济地获得，且人们对于处理这类合金的所知的经验要比其它已知的形状记忆合金更多。NiTi合金还具有相当的弹性并被称为“超级弹性”或“伪弹性”。这种弹性使得本发明装置在布置后回到预设状态。
当按照本发明形成一医疗装置时，一片具有适当尺寸的管状金属纤维织物被插入注塑模中，由此纤维变形以适应在注塑模中的孔和内核的形状。孔的形状是使金属纤维变形成医疗装置所需的形状。使用孔内的内核以进一步在孔内形成纤维的形状。可固定管状金属纤维的线绳末端以防止金属纤维松开。一夹子24，通过焊接或其它紧固方式可固定于线绳末端上。另外，应该知道其它适合的紧固装置也可以另一种方式，例如锡焊、铜焊以及其它非生物排斥性胶泥材料或其它的合适的方式安装于末端上。
在注塑过程中，可将一注塑元件在插入注塑模之前置于管状织物的内腔中，由此进一步界定注塑表面。如果管状金属纤维织物的末端已由夹子或通过焊料而固定，可通过用手将纤维织物线绳分开而将其插入内腔，并将注塑元件插入到管状纤维织物的内腔中。通过使用这样的注塑元件，可以非常精确地控制该医疗装置的最终尺寸并保证纤维合乎注塑孔的尺寸。
注塑元件可由一种材料形成，该材料的选择可使注塑元件消灭或从金属纤维内部移出。例如，注塑元件可由脆的或易碎的材料制成。一旦材料在热处理时与注塑孔和注塑元件接触，注塑元件将被粉碎为许多小块并能容易地从金属织物中移走。如果这种材料是玻璃，注塑元件和金属纤维将会冲击一硬表面，造成玻璃粉碎。然后可将玻璃碎片从金属纤维的包围中移走。
或者，注塑元件可由一可化学溶解或由一化学反应剂分解的材料制成，该化学反应剂基本上不会对金属线绳的特性产生负面影响。例如，注塑元件可由一抗高温塑料树脂形成，该树脂可在一适当的有机溶剂中溶解。在这个例子中，金属纤维和注塑元件可受一热处理以使纤维的形状基本上与注塑孔和注塑元件相一致。于是将注塑元件和金属浸入溶剂中。一旦注塑元件完全溶解，便可将金属纤维织物从溶剂中移走。
必须小心地保证形成注塑元件的材料可承受热处理而不失去其原有形状，至少要等到纤维的形状确定后。例如，注塑元件可由一具有一材料制成，该材料的熔解温度高于线绳成型所需温度，但低于金属线绳的熔解温度。然后使注塑元件和金属纤维受热处理作用，以使金属纤维织物成型，使温度上升到使注塑元件基本上完全熔解，由此将注塑元件从金属纤维织物中移走。
精于此领域的人员可以知道，注塑元件的特定形状产生注塑装置的特定形状。如需要更复杂的形状，注塑元件和注塑模将包括一额外的凸轮结构，但如果形成一更简单的形状，注塑模可以具有很少的部分。在所给模子中部分的数量及其形状将完全由与金属纤维织物基本一致的所需医疗装置的形状所确定。
当管状编织物处于松弛状态时，形成管状编织物的线绳可具有一预定的相对于其它线绳的相对方向。当沿其轴向压缩管状织物时，纤维将背离轴向而张开以顺应注塑模的形状。当纤维织物如此变形时金属纤维的线绳的相对方向将改变。当组装注塑模时，金属纤维织物将与模制面和内孔相一致。在经历形状记忆过程后，所产生的医疗装置具有一预定的松弛结构和收缩结构以及拉伸结构，这使得可穿过一导管或其它类似的传送装置。当纤维织物变形至与注塑模的注塑面基本一致时，松弛结构一般由纤维织物的形状所确定。
一旦将管状纤维织物通过基本与其孔内的注塑面一致的纤维适当定位于一预选模中时，与模制面保持接触的同时纤维织物可能受热处理作用。对镍钛诺线进行适当热处理以形成一所需形状在本领域中是众所周知的。诸如螺旋缠绕镍钛诺之类线圈可用于多个医疗装置中，例如在形成一普遍带有导线末梢链接的线圈，存在有一宽本体以在那样的装置中形成镍钛诺合金，由此在这里无需对在本发明中较佳使用的镍钛诺纤维的热处理参数作详细介绍。简言之，已发现镍钛诺纤维织物可在大约500摄氏度至550摄氏度的温度之间保持1至30分钟，时间长短取决于装置的柔韧度或硬度是否易于使纤维织物处在变形状态，即，使其与注塑孔的注塑面相一致。在一较低的温度下热处理时间将变得更长(如在大约350度的温度下可保持一小时)，较高的温度将使热处理时间变得更短(如在大约900度的温度下只能保持9秒)。可以改变这些参数以适应镍钛诺合金的不同组成成份，在镍钛诺合金的热处理前，熟悉本领域的人员已可知道成品中的镍钛诺的所需特性以及其它因素。
可以知道，无需依赖流对流加热或诸如之类的加热源，在本领域中还可通过施加电流至镍钛诺使其受热。在本发明中，这可通过将电极连接至金属纤维织物各端而完成。然后纤维线通过其电阻热受热以完成所需要的热处理，这将消除将整个注塑模加热至所需热处理温度以加热金属纤维至某一温度的必要。材料、注塑元件和将一管状或平面状金属纤维织物注塑成一医疗装置的方法在美国第5725552号专利中有进一步描述。
使金属纤维在500至550摄氏度的范围内进行热处理，并将线绳的形状确定至一重定位的相对位置，使纤维形状与注塑面一致。当金属纤维织物与从注塑模中移走时，纤维织物将保持与注塑模孔的模制表面一致的形状，由此使医疗装置具有一所希望的确定形状。经热处理后，将纤维织物从与之接触的注塑模孔中移走并基本保持一变形形状。如果使用注塑元件，这种注塑元件将如上所述地被移走。
热处理所需的时间大部分取决于形成的金属纤维织物和模组的材料，但热处理的时间和温度基本上选定在使纤维处在变形状态时的参数，即，使线绳处于其重定位的相对位置，使纤维形状基本上与注塑面一致。热处理所需时间和温度可大幅度地改变，这取决于用来形成线绳的材料。如上面所提到的那样，形成线绳的较佳材料特别较佳的是混有镍钛诺(一种镍钛合金)的形状记忆合金。若使用镍钛诺制成纤维线绳，当金属处于其奥氏体相变状态时，该线绳将具有相当的弹性；这种弹性相变将作为超级弹性或伪弹性被频繁地指出。通过将镍钛诺加热至某一相变温度之上，镍钛诺金属的晶格结构将会趋向于确定纤维的形状并将线绳的相对结构保持在它们在热处理过程中所保持在的位置。
当具有预定形状的装置形成后，该装置可用来治疗病人的生理症状。选择一可用来治疗生理症状的医疗装置。当装置选择完毕后，可用一导管或其它传送装置可置于病人身体的空腔中以将传送装置的末梢置于所需要的治疗处附近。传送装置(未示出)可以采用任何适合的形状但要包括一具有螺纹末梢的细长弹性轴。该传送装置可用来使医疗装置穿过管道内腔并布置于病人体内。当医疗装置在导管末梢的外部布置时，装置仍由传送装置保留。当医疗装置恰好位于病人体内时，金属轴或导线可沿其轴线旋转从而将医疗装置从轴的螺纹端部旋下，即可收回导管和引导线。
通过使医疗装置保持附着于传送装置上，操作者可收回装置以重定位，即使在导管中的装置完全布置后，如果确定装置尚未适当定位。一连接于医疗装置的螺纹夹使操作者当医疗装置布置于导管末梢的外部时能进行控制。当装置离开导管时，装置将趋于弹性地退回至原先较佳的松弛形状。当装置弹回到这种形状时，它可再次作用于导管末梢端，以有效地将其推出导管的端部，由于螺纹夹使操作者可在布置过程中使装置能用手握持，装置的弹性作用可由操作者控制以保证其在布置过程中处在适当位置。
医疗装置可伸长到其收缩结构并插入到导管内腔，装置的收缩结构可以是易于通过导管内腔并在导管末梢外布置的任何形状。例如，装置可具有一相对细长的收缩结构，其中该装置沿其纵向轴伸长。这种收缩结构可单纯通过沿其轴线伸长装置而获得，例如，用手抓住夹子并向两边拉开，这将使基本呈圆柱形的松弛部分向内朝装置轴线的方向收缩。可在植入时将该装置装于导管内，且无需预装导管或引导件。
当装置在病人体内布置时，血栓将聚于线的表面上。由于具有更大的线密度，线的整个面积将会增加，由此增加装置周围的血栓活性。扩张移植物是由一直径为4mm、具有一纬纱数至少约40、倾角至少为30度的管状织物形成，相信该移植物将提供一足够的表面积以在血管中创建一所需空腔。如果需要增加装置的闭合周长，任何种类的溶血栓物可应用于该装置。精通本领域的人员应该懂得闭合膜、纤维或网眼可部分或完全变形而包围装置或在装置内以进一步创造一所需腔体。
如图所示，扩张移植物10的特点是在装置的中心部分延伸有一通道。较佳实施例中的扩张移植装置10包括一管状的、基本上呈圆柱形的本体部分12以及倾斜部分14和16。圆柱部分12包括一在端部14和16间延伸的通道18(参阅图1至图4)。不作为任何限制，在形成装置10的期间，各织线端附着于夹子24。织线端沿周边变形以形成开口端和对夹子24的角度。开口端的14、16的周边上，且末端的形状结合标志22的位置使得末端14、16得以准确定位。精于此领域的人员应该懂得较佳实施例的装置适用于在血管和内部器官内动脉瘤、痿管炎、肿块团之类东西的非外科治疗。
夹子24将线绳在各相应端夹在一起，以将装置10连接至传送系统。在所示实施例中，夹子24中的至少一个是圆柱形的，并具有一可容纳一引导线螺纹端的螺纹孔。夹子24容纳金属纤维织物的织线端以基本防止线的彼此相对移动。那些精于本领域的人员懂得装置10的尺寸与待处理的动脉瘤的尺寸成正比。
下面参阅图7，图中表示本发明另一实施例。装置末端从其圆柱形本体部分12以一定角度延伸，其中至少一端的平面与圆柱部分的纵向轴相交而形成至少一钝角或一锐角，但该夹角没有图1中所示变化地那么剧烈。
图8和图9表示本发明另一实施例，其中一凹孔30形成于装置的中间截面上。图10表示本发明另一实施例，其末端向外张开以使装置产生一更大的宽度。图11表示图10所示装置穿过如图8和图9装置的凹孔30的形式。张开端32抑止装置，使其无法移出凹孔30。对本领域人员而言，如图11所示本发明实施例的结合使用是非常适合于肺支脉的植入或扩张。另外，如图10所示的张开装置可用来避开后降动脉(PDA)之类的东西。
本发明还有一实施例，如图12至14所示，一圆柱本体12弯曲并包括一凹孔36形成于圆柱本体12的弯曲处附近。圆柱本体包括一具有较大直径的第一部分，其尺寸可使其容纳于例如腹部大动脉中；一具有一较小直径的第二部分，其尺寸可使其容纳于例如肠动脉中。并非作为限制，在较佳实施例中第一步分的长度超过第二部分。图14表示类似于标号40、并通过类似于标号42的第二移植物的凹孔36被部分拉长的的一第一移植物。当第一移植物40重新进入松弛状态时，第一和第二移植物一起形成“Y”形移植物。使用时，第二移植物42由已知技术传送至血管“Y”分支中所希望的位置。一第二传送装置延伸入第二分支的一端并延伸出凹孔36。然后第一移植物40被部分释放，同时收回传送装置直至第一植入部分40位于第二移植物42内，如图14所示。“Y”形移植物可以通过“Y”形连接某一血管而用非外科手术方式来治疗动脉瘤、痿管炎、肿块团之类东西。例如，精于本领域的人员应懂得“Y”形移植物可特别用作3A(AAA)植入，从而治愈腹部动脉瘤。
在这里对本发明已作了相当的描述以顺应专利法规并为那些精于此领域的人员提供信息，使其能实施新原理、构造和使用所例示的实施例。然而，应该懂得本发明可通过不同的特定装置而实施，且在不脱离本发明范围的情况下可作多种修改。

Claims (6)

1.一可收缩医疗装置，包括一具有多条织线的纤维织物，所述装置具有近端和末梢端，各端具有安装于其上的装置以固定织线，由此使纤维不至松开，所述装置具有松驰结构，其中，所述松驰结构包括一穿过各端之间中心部分延伸的通道，且在所述松驰结构的至少一端具有一宽度，所述宽度大于松驰部分的中心部分的宽度，所述装置还具有一收缩结构，用来穿过一空腔而进入病人体内。
2.如权利要求1所述装置，其特征在于，所述至少一端包括一沿所述端边缘周围并彼此间隔一预定距离的多个标志。
3.如权利要求1所述装置，其特征在于，所述各端包括沿各所述端各边缘周围并彼此间隔一预定距离的多个标志。
4.如权利要求1所述装置，其特征在于，所述固定装置包括用来安装于传送装置的装置。
5.如权利要求1所述装置，其特征在于，所述装置由一包括多条金属织线的金属纤维织物形成。
6.如权利要求1所述装置，其特征在于，所述固定装置与各所述端的外缘对齐。
CNA2006101110165A 2000-03-27 2001-03-27 可再定位和再获取的血管扩张/移植物 Pending CN1915188A (zh)

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CN1197530C (zh) 2005-04-20
ATE410122T1 (de) 2008-10-15
KR20020082492A (ko) 2002-10-31
DK1994911T3 (da) 2011-12-19
CN1319380A (zh) 2001-10-31
JP2003527925A (ja) 2003-09-24
EP1267750B1 (en) 2008-10-08
CA2403613A1 (en) 2001-10-04
CN1323651C (zh) 2007-07-04

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