CN101072546B - 帮助心脏瓣膜环调整的诊断套件 - Google Patents
帮助心脏瓣膜环调整的诊断套件 Download PDFInfo
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Abstract
用于确定在冠状窦内要求的改变量以降低瓣膜回流的诊断设备。诊断设备包括在其远端端部部分具有远端锚固器(18)的远端管(14)、在其远端端部部分具有近端锚固器(16)的近端管(12)，和相对于近端管移动远端管的调整器。近端管和远端管一起形成了适合于配合在冠状窦内的伸缩延长主体，且设备包括刻度(27)以测量远端锚固器相对于近端锚固器的移动。
Description
本发明涉及用于心脏瓣膜修复的器械和方法，且更特定地涉及使用插入到围绕目标瓣膜的脉管内的设备来帮助用于改进心脏瓣膜功能的心脏瓣膜环调整的诊断套件。
背景技术
心脏瓣膜回流，或从心脏瓣膜的流出侧到流入侧的泄漏在心力衰竭患者中通常发生，且是这些患者中发病率和死亡率的来源。通常的回流在位于左心房和左心室之间的二尖瓣内发生，或在位于右心房和右心室之间的三尖瓣内发生。心力衰竭患者的二尖瓣回流由左心室、乳头肌和二尖瓣环的几何构造改变导致。类似地，三尖瓣回流由右心室、乳头肌和三尖瓣环的几何构造改变导致。这些几何变化导致二尖瓣小叶和三尖瓣小叶束缚和心脏收缩的不完全接合。
心脏瓣膜修复是修正所有病因的心脏回流的选择的过程。通过使用目前的外科技术，取决于外科医生的经验和解剖条件，40％至60％之间的回流的心脏瓣膜可以被修复。心脏瓣膜修复比心脏瓣膜替换的优点被很好地证明。这些优点包括更好的保存心功能且降低了与抗凝血剂相关的出血、血栓栓塞和心内膜炎的风险。
近来已介绍了用于修复心脏瓣膜的不进行外科手术的最小侵入技术的数个进展。这些技术的一些涉及通过冠状窦引入系统用于改造二尖瓣环。
冠状窦是开始于右心房内的冠状口且通过紧邻二尖瓣环的后、外侧和内侧的房室沟的血管。因为冠状窦的位置邻近二尖瓣环，冠状窦提供了用于定位脉管内假体以作用在二尖瓣环上且因此对二尖瓣环再成形的理想管道。
用于心脏瓣膜修复的最小侵入器械的例子可以在如下文献中发现：Solem等的美国专利No.6,210,432，Solem等的在2001年2月5日提交的美国序列号No 09/775,677，Solem等的在2002年11月26日提交的美国序列号No 10/303,765，Solem等的在2002年5月9日提交的美国序列号No 10/141,348，Solem等的在2002年12月24日提交的美国序列号No 10/329,720，Solem等的在2003年11月13日提交的美国序列号No 10/714,462和Solem等的在2003年12月16日提交的美国序列号No 60/530352(′352申请)，所有这些在此通过参考合并。
用于心脏瓣膜修复的最小侵入器械的一个特定的例子在′352申请中更详细地描述且在本文的图10和图11中示出，其包括延长的主体410，具有由桥接件416连接的近端锚固器412和远端锚固器414。近端锚固器412和远端锚固器414都是由镍钛诺制成的支架，且两个锚固器具有网眼构造，包括曲折成形的材料制成的圈54并具有交替的峰42。圈54在每个峰42处连接以形成四边形开口的环部56。近端锚固器412和远端锚固器414在压缩状态和展开状态之间可转换，在压缩状态锚固器的直径小于冠状窦的直径，在展开状态锚固器的直径大约等于或大于冠状窦的直径。
如在图10中示出，桥接件416通过链418、419连接在近端锚固器412和远端锚固器414之间。如在图11中更详细地示出，链419具有基部421和从基部延伸的臂422，且臂422连接到锚固器414。链也包括孔428，孔用作通过其可吸收线420可固定到桥接件的装置。
桥接件416由形状记忆材料制成且是柔性的，以允许主体410顺应冠状窦的形状。桥接件416包括已连接的X形元件424，在邻近的元件424之间具有空间425。桥接件具有激活状态和非激活状态两个状态，在激活状态桥接件416具有第一长度，在非激活状态桥接件具有第二长度，第二长度大于第一长度。可吸收线420用作临时定间隔器，它被织入空间425内以保持桥接件在其较长的非激活状态。
主体插入到患者的冠状窦内，使得两个锚固器412、414处于压缩状态，且包括可吸收线420的桥接件416处于较长的非激活状态。在锚固器412、414放置在希望的位置后，它们被转换到其展开状态，在该状态它们用于将主体410接附到冠状窦。在其间冠状窦壁围绕锚固器412、414生长的时间周期后，可吸收线分解且桥接件416从其较长的非激活状态转换为其较短的激活状态。桥接件416的缩短将近端锚固器412和远端锚固器414拉得更相互靠近，从而拉紧冠状窦且降低其周长。冠状窦的周长降低封闭了导致二尖瓣回流的间隙。
瓣环再成形设备，包括那些以上描述的设备，可以制造为使得它们能在一定尺寸或特征上变化。例如，设备可以制造为使得它们取决于瓣膜所需的再成形量的多少而缩短或另外地改变形状以特定的量。换言之，医师可以在使用严重地改造环的再成形设备、仅略微改造环的再成形设备或被用户定制地设计来以特定的量改造环的再成形设备之间选择。另外，瓣膜再成形设备也可以制造为具有不同的长度和/或锚固器尺寸。因为二尖瓣和三尖瓣小叶接合的严重程度的变化以及心脏瓣膜环的变化的尺寸和长度，有利的是医师在插入瓣膜再成形设备前知晓瓣膜环所需的再成形的多少以及具有环的尺寸和长度如何的概念。此信息将允许医师选择能以合适的量再成形瓣膜环的设备。因此，需要这样的设备，即医师可以使用该设备测量心脏瓣膜环所需的再成形的量和/或环的尺寸和长度。这样的设备将允许医师选择更近似地接近该特定患者所需的再成形的量的环再成形设备以插入到患者体内，以及选择可以用户定制地设计的设备以配合患者环的尺寸和长度。
发明内容
披露了用于确定在心脉管内希望的改变量以降低瓣膜回流的诊断设备。诊断设备包括具有接附在其远端端部的远端锚固器的远端管(或其他合适的延长主体)、具有接附在其远端端部的近端锚固器的近端管(或其他合适的延长主体)和通过它可以相对于近端管移动远端管的调整器。在一个实施例中，设备可以插入到冠状窦内。近端管和远端管一起形成了适合于配合在冠状窦内的伸缩延长主体。另外，远端管包括多个在其上均匀地间隔开的辐射透不过的标记以提供用于测量远端管相对于近端管移动的距离的装置，远端锚固器和近端锚固器在压缩状态和展开状态之间可转换，且调整器以特定距离的移动导致远端管以相同距离的移动。近端锚固器和远端锚固器可以是球囊、篮或支架。
也披露了用于确定对冠状窦需要的改变量以降低二尖瓣回流的方法。这样的方法包括：将诊断设备插入到冠状窦内，将远端锚固器锚定到冠状窦，将近端锚固器锚定到冠状窦，使用调整器来向近端移动远端锚固器使得二尖瓣回流降低，和测量远端锚固器的向近端的移动和同时测量二尖瓣回流的量。
附图说明
图1是二尖瓣和冠状窦的三维视图。
图2是本发明的诊断设备的一个典型的实施例的侧视图，包括带有处于压缩状态的近端锚固器的近端管和带有处于压缩状态的远端锚固器的远端管。
图3是图2的实施例的侧视图，包括处于展开状态的近端锚固器和远端锚固器。
图4a是本发明的伸缩的近端管和远端管的截面视图。
图4b是本发明的远端管的截面视图。
图5是本发明的同轴近端管和远端管的截面视图。
图6是根据本发明的替代的锚固器的透视图。
图7是图2的诊断设备的侧视图，图示为在设备已最初插入到冠状窦内且在远端锚固器展开前。
图8是图2的诊断设备的侧视图，设备定位为使用在冠状窦内使得远端锚固器和近端锚固器在展开状态。
图9是图2的诊断设备的侧视图，图示为在设备已用于降低二尖瓣小叶之间的前后距离后。
图10是近来的二尖瓣修复设备的典型的实施例。
图11是图10的二尖瓣修复设备的细节。
具体实施方式
虽然以下描述的设备和方法可以用于任何合适的心脏瓣膜环内，但为设备和方法的解释的容易和一致性，如下描述将特定地参考二尖瓣和二尖瓣环。
参考图1，冠状窦20从右心房22和冠状口24延伸，且包绕二尖瓣26。术语冠状窦在此用作一般术语以描述静脉返回系统的部分，该部分位于邻近沿房室沟的二尖瓣26。在此使用的术语冠状窦20一般地包括冠状窦、大心静脉和前室间静脉。二尖瓣环28是围绕二尖瓣孔的组织的部分，数个小叶接附到该二尖瓣孔。二尖瓣26具有两个小叶，即前小叶29和后小叶31。后小叶具有三个扇贝状结构P1、P2和P3，在健康的二尖瓣内它们与前小叶29接合以防止血液通过瓣膜的回流。
当二尖瓣环28的后面扩大且将后小叶扇贝状结构P1、P2或P3的一个或多个从前小叶29移开从而导致形成了回流通过其发生的间隙时，经常导致二尖瓣回流的问题。为降低或消除二尖瓣回流，因此希望的是在前方向上移动二尖瓣环28的后面且封闭由小叶位移导致的间隙。
如在图2和图3中示出，本发明的诊断设备10的实施例包括近端管12和远端管14。诊断设备10的尺寸可以使得它能插入到邻近心脏瓣膜的脉管内，例如插入到冠状窦和前右心室心静脉内。另外，诊断设备10可以是足够柔性的以允许它适合于它插入到其内的脉管的曲率。
如在图4a中示出，近端管12可以是具有管内腔35和膨胀内腔37两个内腔的塑料管。管内腔35允许远端管14通过近端管12。膨胀内腔37用作通道，通过它或由它膨胀气体或液体可以展开锚固器，如也在下文中更详细地描述。当锚固器是可膨胀的时，例如是球囊时可以使用此管构造。在一个优选的结构中，近端管由外径为大约0.130英寸的尼龙管路形成。管内腔35优选地具有大约0.085英寸的直径。在一个替代实施例中，在近端管内的膨胀内腔可以形成为新月形或椭圆形的形状。在另一个替代的实施例中，近端管可以形成有两个或更多的膨胀内腔以增加截面流动面积。在再另一个替代的实施例中，近端管的近端部分可以与塑料应力释放管路和用于与管内腔和膨胀内腔连通的毂配合。
如在图4b中示出，远端管也可以包括引导丝内腔19和膨胀内腔21两个内腔。引导丝内腔19用作当远端管14插入到患者体内时可在其上行进的通道，如将在下文中更详细地描述。在一个优选的实施例中，引导丝内腔19形成有大约为0.042英寸的直径。膨胀内腔21用作通过它或由它膨胀气体或液体可以使锚固器膨胀的通道，也将在下文中更详细地描述。当锚固器是可膨胀的时，例如是球囊时可以使用此管构造。
在一个优选的构造中，远端管由外径为大约0.067英寸的Pebax55D管路形成。引导丝内腔19优选地具有大约0.042英寸的直径。在一个替代实施例中，远端管内的膨胀内腔可以形成为新月形或椭圆形形状。在再另一个替代实施例中，远端管可以形成有两个或更多的膨胀内腔以增加通过管的截面流动面积。在又另一个替代实施例中，远端管的近端部分被内径为大约0.0725英寸且外径为大约0.0780英寸的不锈钢编织聚酰胺管路围绕，以硬化近端部分且增强可推动性。近端部分也可以与毂配合，用于与引导丝和膨胀内腔连通。
图5示出了替代构造，其中远端管14包括同轴的内管68和外管66。基于此构造，引导丝内腔64形成在内管68内且膨胀内腔62形成在内管和外管66之间。当锚固器是可膨胀的时，例如是球囊时，或例如是篮的机械地可展开的时，可以使用此管构造。此同轴管构造也可以用于近端管12。也将认识到的是，在一些构造中，近端管12通过远端管，而非反之，如上所描述。
远端管14可以进一步包括辐射透不过的标记带27，标记带27沿管的外周间隔开，如在图2中示出。标记带27在荧光透视中可见，当管定位在脉管内时，标记带27用于指示远端管14的位置。另外，标记带27可以用于测量冠状窦的希望的部分和由远端管14的移动量，如在下文中更详细地描述。标记带27可以是铂带或在荧光透视或其他合适的视觉装置下可见的任何其他生物相容性的带。沿远端管14所包括的带27的特定的个数不是关键的，但优选地具有足够个数的带以允许在冠状窦内的管的整个暴露的长度在荧光透视下可见。在一个优选的实施例中，远端管包括沿远端端部部分大约14cm布置的标记带。标记带优选地间隔开大约1cm。进一步地，存在足够个数的带27以允许带作为用于远端管14的移动的距离标记。类似的个数的标记位于患者体外由人眼可见的远端管上。这些标记是可见的且即使在无荧光透视帮助下也能计数。
远端管14也包括位于远端管的远端端部处或附近的远端锚固器18。在一个实施例中，远端锚固器18具有压缩状态和展开状态两个状态。在压缩状态中，远端锚固器18可插入到冠状窦20内或其他冠状脉管内。在展开状态，远端锚固器18将远端管14固定到它已插入到其内的脉管的内壁。远端锚固器18可通过转换装置从压缩状态转换到展开状态。这样的转换装置可以是机械的、电气的或化学的。另外，远端锚固器18可以是自展开的。
如在图2和图3中示出，在一个典型实施例中，远端锚固器18是顺应性的球囊，它顺应了远端锚固器18展开到其内的脉管的尺寸和形状。球囊可以通过热结合或粘附结合，或通过任何其他合适的接附装置接附到远端管或近端管。球囊可以制造为使得它具有安全机构，安全机构将降低球囊损坏它所插入到其内的脉管的可能性。例如，球囊可以设计为具有它可以膨胀到的最大压力。另外，球囊可以设计为带有逐渐地降低其内部压力的“缓慢泄漏”。因为顺应性球囊将顺应脉管的尺寸且因为球囊在荧光透视下可见，观察者将能通过在具有尺寸标记的显示屏上观察球囊来确定在球囊位置处的脉管的尺寸。获知瓣膜修复设备将插入到其内的脉管的近似尺寸可以允许更精确的确定应从设备的序列中选择哪个特定的瓣膜修复设备以使用在患者上。在一个优选的构造中，远端锚固器18是由Pebax 55D形成的顺应性球囊且具有大约20mm的长度。顺应性球囊优选地具有已膨胀的直径的范围从1大气压下4mm至8大气压下大约9mm。在替代的构造中，球囊可以由任何其他合适的材料形成，例如尼龙、聚氨酯和聚乙烯。在一个实施例中，远端管路进一步提供有防止损伤的远端尖端。远端尖端优选地由Pebax 40D制成。在诊断设备10的其他替代的实施例中，远端锚固器18可以是篮、支架或任何其他适合于将设备固定在脉管内的可展开设备。
球囊可以通过使用生物相容性流体，且更特定地使用盐水溶液从其压缩状态转换到展开状态。流体可以通过导管(未示出)引入且可以通过膨胀内腔21、62(图4和图5)运输到球囊。
在如图6中示出的替代的实施例中，篮30可以用作远端锚固器。在一个实施例中，篮30具有压缩状态和展开状态两个状态。在压缩状态中，篮30可插入到冠状窦或其他冠状脉管内。更特定地，在压缩状态中，篮30可以大体上是圆柱形的且可以包括从篮的近端端部34纵向地延伸到篮的远端端部36的多个束32，束32绕篮的圆周均匀地间隔开。篮30的远端端部36可以适合于配合在内管68上且篮的近端端部34可以适合于配合在外管66上(见图5)。在一个实施例中，外管66也可以是远端管14。当内管68和外管66相对于彼此移动时，篮30可以展开或收缩。在展开状态中，篮30固定到它已插入到其内的脉管的内壁。在其中篮30的近端端部34和远端端部36之间的距离被缩小的展开状态中，束32可以变成三角形形状的，使得三角形的顶点从篮的中心突出。在一个典型的实施例中，束32可以由形状记忆材料(例如镍钛诺)制成，从而允许篮30通过例如覆盖了篮的鞘(未示出)的收回从其压缩状态转换到其展开状态。
类似于远端管14，近端管12可以具有位于近端管的远端端部处或附近的近端锚固器16。类似于锚固器18，近端锚固器16可以具有用于输送到脉管内的压缩状态和用于将远端管锚定到脉管的展开状态。近端管12可以进一步包括膨胀内腔37以用于在压缩状态和展开状态之间转换近端锚固器16。在一个优选构造中，近端锚固器16是具有大约30mm的长度且由聚氨酯形成的球囊。在替代构造中，球囊可以由任何其他合适的材料形成，例如尼龙、Pebax和聚乙烯。
诊断设备10的远端管14和近端管12可以以伸缩方式可滑动地相互连接以形成延长主体。在一个典型的实施例中，近端管12的外径大于远端管14的外径，从而允许远端管配合在近端管内。远端管14的移动可以通过使用手柄(未示出)控制。更特定地，远端管14可以接附到可沿手柄滑动的轴圈。当轴圈向近端移动时，远端管14也向近端移动相同的距离。类似地，当轴圈向远端移动时，远端管14也向远端移动相同的距离。在一个典型的实施例中，手柄的主体可以包括距离标记，它允许测量轴圈的移动且因此允许测量远端管14的移动。
在一个典型的实施例中，诊断设备10可以如下部置。首先，引导丝(未示出)插入到冠状窦内通过大心静脉且深入到房室静脉内。诊断设备10可以同轴地安装在输送导管(未示出)上，且在引导丝上插入到冠状窦20内。远端管14和近端管12的近端端部可以延伸到使用者体外，在此它们接附到手柄。另外，当诊断设备10插入到冠状窦20内时，近端锚固器16和远端锚固器18邻近。
当最初插入到患者体内时，诊断设备10尽可能向远端地插入到冠状窦20内。特定地，诊断设备10可以插入到已知为大心静脉46的冠状窦的部分内，如在图7中示出。由于其自然地弯曲形状和较高浓度的脂肪组织，大心静脉46允许了对移动的高的阻力，且提供了用于远端锚固器18的自然锚定位置。
一旦远端管14，且更特定地远端锚固器18已放置在冠状窦20内的希望的位置，则远端锚固器可以从其压缩状态转换为其展开状态。在其中远端锚固器18是球囊的一个实施例中，生物相容性流体将被引入到膨胀内腔37内以使球囊膨胀。在其中远端锚固器18是例如篮30(图6)的机械地可展开锚固器的替代的实施例中，内管68和外管66(图5)的操纵将导致锚固器转换到其展开状态。在其中锚固器是自展开锚固器的又另一个实施例中，输送鞘用于覆盖锚固器且输送鞘的收回将导致锚固器转换到其展开状态。
一旦远端锚固器18已展开为使得锚固器与冠状窦20的内壁接触，则使用手柄向近端拉动近端管12。在手柄上的距离标记以及在远端管14上的辐射透不过的标记27允许测量近端管12已移动的距离。向近端拉动近端管12直至近端锚固器16邻近冠状窦20的口24。替代地，近端锚固器可以放置在冠状窦口24外的右心房内，邻接口但不阻断口。在远端管14上的辐射透不过的标记27在监视屏上可见且帮助使用者将近端锚固器16定位在冠状窦20内。在近端锚固器16放置在其希望的位置后，近端锚固器从其压缩状态转换到其展开状态(图8)。如上所述，在其中近端锚固器16是球囊的实施例中，生物相容性流体将被引入到膨胀内腔21内以使球囊膨胀。在其中近端锚固器16是例如篮30(图6)的自展开锚固器的实施例中，邻近近端锚固器的输送鞘的收回将导致锚固器转换到其展开状态。
一旦近端锚固器16和远端锚固器18二者已从其压缩状态转换到其展开状态，则手柄可以用于将远端管14向近端拉动。将远端管14向近端拉动将具有在冠状窦20上的两个效果的至少一个效果。第一个效果可以是将冠状窦20拉紧得绕二尖瓣26更紧，降低前小叶29和后小叶31之间的距离。第二个效果可以是降低冠状窦20的曲率半径，这也可以降低前小叶29和后小叶31之间的距离。此二尖瓣26的形状改变允许在前小叶29和后小叶31之间的由二尖瓣回流导致的间隙被封闭(图9)，因此降低或消除了二尖瓣回流。
当冠状窦的曲率半径减小且在二尖瓣的前小叶29和后小叶31之间的间隙减小时，测量了回流的量。此测量优选地用放置在患者的胸部上、食道内或心脏内的超声探头通过超声进行。当回流处于最小值时，且特别地当无回流时，记录远端管14相对于近端管移动的距离，例如通过使用辐射透不过的标记作为测量工具。
一旦二尖瓣回流已消除或降低了希望的值且远端管14必须移动以实现希望的效果的距离被测量，则将远端锚固器18和近端锚固器16从其展开状态转换回其压缩状态。在其中锚固器16、18是球囊的实施例中，用于膨胀球囊的流体被移开。在其中锚固器16、18是自展开锚固器的实施例中，将输送鞘再次插入超过每个锚固器。在其中锚固器16、18是篮30的实施例中，内管68和外管66相互移开以将锚固器转换到其压缩状态。
在近端锚固器16和远端锚固器18已返回其压缩状态后，近端管12和远端管14向近端沿引导丝从冠状窦20收回且收回到患者体外。一旦诊断设备10已移开，则瓣膜修复设备可以沿引导丝插入以更永久地修复二尖瓣回流。基于从诊断设备10接收的关于冠状窦20的信息，例如冠状窦的长度，和关于实现希望的二尖瓣回流降低所需要的缩短量的信息，可以从具有多种(或可变)直径和/或缩短长度的这样的设备序列中选择合适的瓣膜修复设备。
虽然以上描述了本发明的优选实施例，但对本领域技术人员显见的是多种替代、修改和等价物可以在附带的权利要求书的范围内实施。
Claims (12)
1.一种用于确定在冠状窦内要求的调整量以降低心脏瓣膜回流的诊断设备，其包括：
第一延长主体，在第一延长主体远端端部部分具有远端锚固器，
第二延长主体，在第二延长主体远端端部部分具有近端锚固器，和
调整器，以将第一延长主体和第二延长主体的一个相对于第一延长主体和第二延长主体的另一个移动，
其中第一延长主体和第二延长主体一起形成了适合于配合在冠状窦内的伸缩延长主体，和
进一步包括刻度以允许测量远端锚固器相对于近端锚固器的移动。
2.根据权利要求1所述的诊断设备，其中刻度在延长主体上。
3.根据权利要求2所述的诊断设备，其中刻度是多个标记。
4.根据权利要求3所述的诊断设备，其中标记沿延长主体均匀的间隔开。
5.根据权利要求1所述的诊断设备，其中刻度在调整器上。
6.根据权利要求1所述的诊断设备，其中远端锚固器和近端锚固器在压缩状态和展开状态之间可转换。
7.根据权利要求1所述的诊断设备，其中调整器移动一定距离导致第一延长主体移动相同距离。
8.根据权利要求1所述的诊断设备，其中远端锚固器和近端锚固器是球囊。
9.根据权利要求8所述的诊断设备，其中远端锚固器和近端锚固器通过流体从其压缩状态转换到其展开状态。
10.根据权利要求1所述的诊断设备，其中远端锚固器是篮。
11.根据权利要求1所述的诊断设备，其中第一延长主体和第二延长主体的每个包括膨胀内腔和引导丝内腔。
12.根据权利要求1所述的诊断设备，其中调整器是手柄。
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| US6997951B2 (en) * | 1999-06-30 | 2006-02-14 | Edwards Lifesciences Ag | Method and device for treatment of mitral insufficiency |
| FR2826863B1 (fr) | 2001-07-04 | 2003-09-26 | Jacques Seguin | Ensemble permettant la mise en place d'une valve prothetique dans un conduit corporel |
| ATE462378T1 (de) * | 2001-12-28 | 2010-04-15 | Edwards Lifesciences Ag | Speichervorrichtung mit verzögerung |
| US7854761B2 (en) | 2003-12-19 | 2010-12-21 | Boston Scientific Scimed, Inc. | Methods for venous valve replacement with a catheter |
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2005
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- 2005-12-09 JP JP2007545613A patent/JP2008522749A/ja not_active Withdrawn
- 2005-12-09 WO PCT/US2005/044373 patent/WO2006063108A1/en active Application Filing
- 2005-12-09 AU AU2005314020A patent/AU2005314020B2/en not_active Ceased
- 2005-12-09 EP EP05853317A patent/EP1827316A1/en not_active Withdrawn
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Also Published As
| Publication number | Publication date |
|---|---|
| US20070168023A1 (en) | 2007-07-19 |
| CN101072546A (zh) | 2007-11-14 |
| CA2587930A1 (en) | 2006-06-15 |
| US20060129051A1 (en) | 2006-06-15 |
| US7806928B2 (en) | 2010-10-05 |
| US7211110B2 (en) | 2007-05-01 |
| WO2006063108A1 (en) | 2006-06-15 |
| JP2008522749A (ja) | 2008-07-03 |
| EP1827316A1 (en) | 2007-09-05 |
| AU2005314020A1 (en) | 2006-06-15 |
| AU2005314020B2 (en) | 2011-05-19 |
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