CN101959464A - 用于血管治疗的扭绞初级线圈 - Google Patents
用于血管治疗的扭绞初级线圈 Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
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Abstract
一种柔性金属导线线圈通过在特殊心轴上形成初级线圈来以扭绞线圈模式形成,所述心轴是由围绕纵向轴线螺旋状地扭绞以具有螺旋形状的两根或更多根材料股线形成的。所述初级线圈导线缠绕在所述心轴上以使所述初级线圈具有对应于所述心轴的所述螺旋形状的扭绞形状。
Description
相关申请的交叉引用
本申请是基于2007年8月17日提交的美国临时申请60/956,509。
技术领域
本发明一般地涉及用于血管介入治疗处理或血管外科的可植入设备,且更具体地涉及具有扭绞模式的线圈,所述线圈沿着所述线圈的长度方向展示了改进的柔韧性和/或次级线圈成形能力,所述线圈作为初级线圈对在各种血管介入治疗中使用的更复杂的形状特别有用。
背景技术
血管闭塞设备可以具有多种配置,并且通常由一个或多于一个元件形成,所述元件在展开配置中比它们在放置之前处于输送导管内时更大。一个广泛使用的血管闭塞设备是具有次级展开配置的螺旋状导线线圈,其尺寸可以设计为阻塞所有或一部分感兴趣的脉管系统的特定部分。已知一个解剖成形的血管闭塞设备使其自身形成为解剖腔(例如动脉瘤)的形状并且由柔性材料(例如铂合金)的预成形初级线圈制成。
可以设计血管闭塞构件的尺寸和形状,使得在它们的展开配置中适配在血管腔或囊内以便用于动脉瘤或瘘管的治疗。血管闭塞构件首先可以以大致线性方式螺旋状地缠绕并且接着围绕心轴或外形缠绕,所述心轴或外形成形为与所期望的次级形状一致并且被加热处理以在从所加热的外形中移走之后保持心轴的基本形状。
沿着线圈的某些预定部分更容易变形的可变硬度线圈可能在填充各种尺寸和形状的动脉瘤时是有用的。已知可变剖面圆锥形血管闭塞线圈可以通过在线圈不同区域的直径的变化或线圈组成成分的变化来实现线圈硬度的变化。
形成初级缠绕线圈的已知方法是在典型直径大约为0.010英寸的圆柱形导线心轴上缠绕金属导线(例如铂导线)的连续线圈。因为其形成为围绕恒定直径的圆柱形心轴的螺旋状,所以产生的初级缠绕线圈典型地在所有方向上都具有相同的弯曲硬度,使得线圈在沿着线圈的纵向轴线的所有平面上都具有围绕线圈的纵向轴线的恒定弯曲力矩。
期望提供一种柔性金属导线线圈,将其作为结构元件用来形成例如致密填充(densely packed)的治疗血管闭塞线圈或凝块去除器,所述柔性金属导线线圈在保持较小线圈的软度的同时允许线圈在展开并更充分地填充和占领给定空间之前是柔性的,并且可以使线圈的输送更容易。还期望提供一种初级缠绕线圈,其不具有特殊的松弛形状,使得可以比当前可用的初级缠绕线圈更充分地填充要治疗的区域。本发明满足这些需要和其他需要。
发明内容
简要地并且以普通术语来说,本发明提供了柔性金属导线线圈、形成所述线圈的方法、用于形成所述线圈的心轴和用于形成所述心轴的方法,所述柔性金属导线线圈在动脉瘤等中展示了比常规初级线圈更好的填充密度(packing density),且本发明的线圈具有扭绞线圈模式。
在第一当前优选的实施例中,本发明提供了具有非圆形剖面形状的致密的初级缠绕线圈,该非圆形剖面形状沿着横穿线圈的纵向轴线的至少一个轴线伸长,其中所述至少一个横向轴线沿着纵向轴线旋转,以提供具有沿着纵向轴线进动的至少一个弯曲力矩的初级缠绕线圈。初级缠绕线圈的剖面形状可以是例如椭圆形、长方形、三角形或某些其他几何形状。在另一当前优选方面中,由柔性伸长的材料股线(例如金属或金属合金)形成初级缠绕线圈。在当前优选实施例中,金属是铂合金。该柔性伸长的材料股线可以具有例如大约0.0015英寸至0.002英寸的直径。初级缠绕线圈还可以形成为具有次级形状,例如球形、类球形、圆锥形或圆柱形的次级形状,或这类形状的组合。在另一当前优选方面中,初级缠绕线圈的至少一个进动横向轴线提供了具有至少一个进动弯曲力矩的初级缠绕线圈,使得初级缠绕线圈的最小弯曲力的平面沿着初级缠绕线圈的长度方向变化,因此当线圈用作治疗血管闭塞线圈、凝块去除器或其他治疗设备时,允许线圈的展开形状为高度致密配置,并且与具有对称剖面的线圈相比具有较高的填充百分比和较高的组装密度。在另一方面,初级缠绕线圈限定了内部空间,并且轴向元件可以布置在初级缠绕线圈的内部空间中以增加沿着初级缠绕线圈的纵向轴线延伸的其他元件的拉伸阻力,使得可以将初级缠绕线圈用作可收回的凝块去除器。轴向元件可以由抗拉伸塑料线或金属(例如镍钛诺)形成,并且也可以被配置成在其松弛状态下具有次级形状。
在形成根据本发明用于制作血管闭塞线圈的心轴的方法中,心轴形成为具有沿着横穿纵向轴线的至少一个轴线伸长的非圆形剖面形状,其中所述至少一个横向轴沿着纵向轴线进动,也就是说当它沿着纵向轴线前进时围绕该纵向轴线旋转。在心轴的一个当前优选构造中,两个或多于两个平行导线股线可以围绕纵向轴线螺旋状地扭绞,以提供具有为多螺旋形状的外部表面的多螺旋心轴。在当前优选的方面,扭绞两个或多于两个平行材料股线的步骤包括围绕纵向轴线扭绞平行材料股线,使得以双螺旋形状形成心轴。类似地,可以沿着纵向轴线扭绞三个或多于三个股线以生成具有三角形、正方形或其他剖面的心轴。在另一方面,被扭绞以形成心轴的多个材料股线是由金属导线(例如弹簧导线,典型地是不锈钢导线)形成的,但是其他类似金属或高分子材料也可以是适合的。多根材料股线可以具有大约0.0035英寸到大约0.055英寸的直径,使得心轴可以具有大约0.0070英寸到大约0.11英寸的直径。在本发明的另一方面,可以用具有期望的非圆形剖面的单根导线构建心轴,然后该导线心轴围绕其纵向轴线扭绞以形成心轴的最终期望形状。类似地,可以以可变的纵向间距形成心轴,以生成在线圈的某些部分具有与其他部分相比可变的弯曲力矩的初级线圈。
在根据本发明形成血管闭塞线圈的一个当前优选方法中,柔性金属导线围绕心轴的长度方向缠绕以形成具有对应于心轴外部表面的多螺旋形状的扭绞形状的初级缠绕线圈。在另一方面,也可以将轴向构件沿着初级缠绕线圈的纵向轴线插入初级缠绕线圈的内部空间,以提供拉伸阻力或者使得易于使用初级缠绕线圈作为凝块去除器。
本发明提供了线圈的结构、制造方法以及制造用于生成线圈的心轴,所述线圈可以被改造(tailor)为提供体腔的闭塞所期望的各种各样的特性,包括腔体的较大填充和在形成次级形状中的更好行为,包括在形成次级形状中的“随机断裂”,以更容易地容纳非一致动脉瘤等。从以下详细描述和通过示例方式图示说明本发明的特征的附图中,本发明的这些和其他方面和优势将变得明显。
附图说明
图1A是根据本发明图示说明轴杆中的一对平行核心股线的布置和扭绞的示意图,其准备用于制作用于形成具有扭绞形状的初级缠绕线圈的扭绞心轴的一种形式。
图1B是根据本发明图示说明围绕具有双螺旋形状的扭绞心轴的长度方向缠绕柔性金属线圈导线的示意图,以此形成具有扭绞形状的初级缠绕线圈,所述扭绞形状具有沿着纵向轴线进动的横向轴线。
图2是具有图1B的双螺旋形状的扭绞心轴的长度方向的放大图。
图3A是根据本发明图示说明初级缠绕线圈的长度方向的侧面正视图的示意图,所述初级缠绕线圈被显示为围绕具有图1B的双螺旋形状的扭绞心轴缠绕(出于图示说明目的以宽间距显示),用于将具有沿着线圈的纵向轴线进动的一个横向轴线的扭绞模式赋予线圈。
图3B是根据本发明的紧密缠绕的初级缠绕线圈的长度方向的侧面正视图,所述初级缠绕线圈被显示为围绕扭绞心轴缠绕(心轴被移走),并且将具有沿着一个横向轴线伸长的扭绞图案通过心轴赋予线圈,所述横向轴线沿着纵向轴线进动。
图4是形成为具有扭绞形状的初级缠绕线圈的侧面正视图,该扭绞形状形成为圆柱形次级形状。
图5是沿着图3B的线5-5的剖面图,其示出初级缠绕线圈的横向轴线沿着纵向轴线的进动。
图6是沿着图3B的线6-6的剖面图,其示出初级缠绕线圈的横向轴线沿着纵向轴线的进动。
图7是沿着图3B的线7-7的剖面图,其示出初级缠绕线圈的横向轴线沿着纵向轴线的进动。
图8是沿着图3B的线8-8的剖面图,其示出初级缠绕线圈的横向轴线沿着纵向轴线的进动。
图9是与图5的剖面图类似的剖面图,其示出插入初级缠绕线圈的内腔中的伸长的材料股线。
图10是插入以填充动脉瘤的大致球形次级成形模型的常规初级缠绕线圈的侧面正视图。
图11是插入以填充动脉瘤的大致球形次级成形模型的、形成为具有扭绞纵向形状的常规初级缠绕线圈的侧面正视图,其示出用本发明的线圈时的动脉瘤的较大填充。
图12是根据本发明的紧密缠绕的初级缠绕线圈的长度方向的侧面正视图,所述初级缠绕线圈具有沿着两个横向轴线伸长的扭绞形状,这两个横向轴线沿着纵向轴线进动。
图13是根据本发明的图12的初级缠绕线圈的透视图,所述初级缠绕线圈具有沿着两个横向轴线伸长的扭绞形状,这两个横向轴线沿着纵向轴线进动。
图14是根据本发明具有扭绞形状的图12的初级缠绕线圈的端视图,其示出沿着两个横向轴线伸长的扭绞形状,这两个横向轴线沿着纵向轴线进动。
图15是与图12类似的、紧密缠绕的初级缠绕线圈的长度方向的侧面正视图,其示出初级缠绕线圈的一个缠绕间距和循环间距,所述初级缠绕线圈具有沿着两个横向轴线伸长的扭绞形状,这两个横向轴线沿着纵向轴线进动。
具体实施方式
如在作为说明而不是作为限制的附图中所示,本发明提供在图1B、图3A和图12至图15中示出的具有扭绞线圈模式的初级缠绕柔性金属导线线圈10。参考图1A和图1B,根据本发明的方法,可以通过在具有中心纵向轴线16的伸长的多螺旋或扭绞心轴14上缠绕伸长的柔性材料股线(例如柔性导线12,由金属或金属合金形成)来将扭绞线圈模式赋予初级缠绕线圈。在图1A中示出的一个当前优选形式中,伸长的多螺旋或扭绞心轴可以由多个平行核心股线(例如一对平行核心材料股线18和20)形成,所述核心材料股线已经围绕心轴的纵向轴线螺旋地缠绕或扭绞,因此使心轴具有多螺旋形状,例如图1B和图2中所示的双螺旋状,即当由围绕心轴的纵向轴线扭绞的两个平行核心股线形成为扭绞螺旋状(helix)或螺旋形(spiral)的心轴时的情况。如图1A和图1B中所示,平行核心股线18和20的相对端可以固定到轴杆的相对夹盘19并且将扭绞以提供具有期望的扭绞循环间距的心轴。
扭绞在一起的心轴核心材料股线典型地是圆金属导线,例如不锈钢弹簧导线,但是心轴核心股线也可以由聚合物材料组成,例如聚乙烯。可以由一对扭绞的平行圆核心股线预形成多螺旋形状的扭绞的心轴,每一平行圆核心股线具有小到大约0.0035英寸到0.005英寸的直径,形成直径为大约0.007英寸到0.010英寸的心轴,或者例如每一平行圆核心股线具有大到大约0.055英寸的直径,形成直径为大约0.11英寸的心轴。
可以通过缠绕柔性伸长的材料股线,例如铂导线或铂合金(例如铂钨),在扭绞的心轴上形成初级缠绕线圈。例如,可以通过具有大约为0.0015英寸到0.002英寸的外径的铂钨合金(PT-W)导线或具有大约为0.0015英寸到0.002英寸的外径的铂导线围绕扭绞心轴的长度方向缠绕来形成初级缠绕线圈,典型地在纵向上沿着心轴具有每英寸大约500圈的柔性金属导线。围绕这种多螺旋扭绞心轴缠绕这种伸长的柔性股线产生如图3B所示的、具有对应于扭绞心轴的多螺旋形状的大致扭绞形状或模式的初级缠绕线圈。如图5至图8所示,产生的初级缠绕线圈具有沿着横穿纵向轴线的横向轴线21伸长的非圆形剖面形状。横向轴线沿着纵向轴线进动,以提供具有也围绕纵向轴线进动的相关弯曲力矩的初级缠绕线圈。以此方式形成的初级缠绕线圈的剖面形状可以是例如椭圆形或长方形。因此初级缠绕线圈的扭绞形状或模式有利地提供了具有可变弯曲力矩的初级缠绕线圈,可变弯曲力矩在此定义为最小弯曲力的平面,因此其沿着初级缠绕线圈在不同方向或平面上变化。
虽然没有示出,但是本领域技术人员应明白,也可以由椭圆形、三角形或其他剖面的导线来形成心轴,所述椭圆形、三角形或其他剖面的导线围绕其纵向轴线扭绞以提供在此描述的针对完全由圆形剖面导线形成的心轴的特性。
如图4所示,可以通过例如围绕合适的圆柱形心轴(未示出)缠绕初级缠绕线圈并且使用加热来设置线圈中的圆柱形心轴的圆柱形形状,以此来形成具有次级形状22(例如圆柱形次级形状)的线圈。替换地,如图10和图11所示,次级形状可以是球形或类球形次级形状,其可以通过围绕合适的球形或类球形心轴(未示出)缠绕初级缠绕线圈并且使用加热设置来自线圈中的球形或类球形心轴的次级球形形状来形成。此外,如图9所示,可以将伸长的材料股线23(例如成形或未成形的导线,例如镍钛诺导线)或由聚合物材料(例如聚乙醇酸或聚丙烯)形成的抗拉伸构件插入大致管状成形的初级缠绕线圈的内腔,以此增强初级缠绕线圈以对线圈提供较大的拉伸阻力或允许初级缠绕线圈被用作例如可收回的凝块去除器。
在下表中提供了具有次级圆柱形状的线圈的示例性尺寸:
外径(毫米) 长度(厘米)
6 26
7 30
8 29
现在参考图10,该图示出了当使用不带次级形状的对称初级线圈来填充动脉瘤时用玻璃形成的示例性动脉瘤的填充。如从图示中可以看出的,初级线圈关于其纵向轴线的对称性导致了线圈在动脉瘤内形成层,这导致了填充动脉瘤时出现空隙。图11示出了当使用本发明的线圈时同类型的动脉瘤模型的改进填充比例。由于弯曲力矩沿着线圈的纵向轴线进动(其导致了动脉瘤的较大“填充比例”),本发明的线圈具有“随机断裂”特性。这种特性在仍然能够以单一类型的线圈完成处理的同时,也允许在动脉瘤或具有不规则形状的其他体腔的处理中具有较大的灵活性。
参考图12至图15,可以通过以下方法使初级缠绕线圈32具有扭绞线圈模式:将由伸长的柔性材料股线34形成的具有圆角的一系列多个大致三角环33结合起来,或通过将伸长的柔性材料股线34(例如由金属或金属合金(例如铂导线或铂合金,例如铂钨)形成的柔性导线)缠绕在具有中心纵向轴线16的伸长的多螺旋或扭绞心轴上,以提供具有扭绞形状以及所期望的扭绞循环间距的初级缠绕线圈32,所述扭绞形状具有沿着纵向轴线进动的大致三角剖面形状和圆角。例如,可以由具有大约为0.0015英寸至0.002英寸的外径的铂钨合金(PT-W)导线或具有大约为0.0015英寸或0.002英寸的外径的铂导线围绕扭绞心轴的长度方向缠绕形成初级缠绕线圈,典型地在纵向上沿着心轴具有每英寸大约20圈的柔性金属导线。例如,对于以大约0.0016英寸间距、大约13-14度的旋转角度缠绕的具有大约0.0015英寸直径的导线,初级缠绕线圈可以具有每个循环大约8至9圈的扭绞循环间距。
如图13至图14所示,根据当前优选实施例的初级缠绕线圈具有沿着与初级缠绕线圈的纵向轴线成角度的横向轴线(例如36、38)伸长的非圆形剖面。这些横向轴线沿着纵向轴线进动,以提供具有也围绕纵向轴线进动的两个相关弯曲力矩(由于与纵向轴线成非对称性,一个比另一个更抗弯曲)的初级缠绕线圈。以此方式形成的初级缠绕线圈的剖面形状通常是例如具有圆角的三角形。因此初级缠绕线圈的扭绞形状或模式有利地提供了具有沿着初级缠绕线圈在不同方向或平面上变化的两个弯曲力矩的初级缠绕线圈。
如上所述,初级缠绕线圈可以形成为具有次级形状(例如圆柱形、圆锥形、球形或类球形次级形状或其组合)的线圈,并且可以将伸长的材料股线(例如成形或未成形的导线(例如镍钛诺导线))或由聚合物材料(例如聚乙醇酸或聚丙烯)形成的抗拉伸构件插入大致管状成形的初级缠绕线圈的内腔,以此增强初级缠绕线圈、帮助线圈抗拉伸或允许初级缠绕线圈被用作例如可收回的凝块去除器。
从前述内容可以明显看出,虽然已经示出并且描述了本发明的特定形式,但是可以进行各种修改而不偏离本发明的精神和范围。因此,除了由随附的权利要求限制本发明之外,无意限制本发明。
Claims (20)
1.一种具有纵向轴线的初级缠绕线圈,包括:
盘绕所述初级缠绕线圈的所述纵向轴线的柔性金属导线,所述初级缠绕线圈沿着所述纵向轴线伸长并且具有非圆形剖面形状,所述非圆形剖面形状的轴线沿着所述纵向轴线进动以形成重复扭绞线圈模式。
2.根据权利要求1所述的初级缠绕线圈,其中所述单个柔性金属导线线圈具有双螺旋的外部形状。
3.根据权利要求1所述的初级缠绕线圈,其中从由椭圆、具有圆角形状的长方形和大致三角形组成的群组中选择所述非圆形剖面形状。
4.根据权利要求1所述的初级缠绕线圈,其中所述非圆形剖面形状沿着与所述纵向轴线成角度的至少一个横向轴线伸长,并且其中所述至少一个横向轴线沿着所述纵向轴线进动。
5.根据权利要求4所述的初级缠绕线圈,其中所述非圆形剖面形状沿着横穿所述纵向轴线的一个横向轴线伸长。
6.根据权利要求4所述的初级缠绕线圈,其中所述非圆形剖面形状沿着具有较低弯曲阻力的第一横向轴线和具有较高弯曲阻力的第二横向轴线伸长,所述第一横向轴线和所述第二横向轴线均与所述纵向轴线成角度。
7.根据权利要求1所述的初级缠绕线圈,其中所述柔性金属盘绕导线形成为具有从由圆柱形、圆锥形、球形和类球形及其组合组成的群组中选择的次级形状。
8.根据权利要求1所述的初级缠绕线圈,其中所述初级缠绕线圈具有沿着所述初级缠绕线圈的纵向轴线的内部空间,且还包括沿着所述初级缠绕线圈的所述纵向轴线穿过所述内部空间延伸的轴向材料股线。
9.根据权利要求1所述的初级缠绕线圈,其中所述初级缠绕线圈在所述初级缠绕线圈的不同平面上具有可变的弯曲力矩,使得最小弯曲力的平面沿着所述初级缠绕线圈的长度变化。
10.一种次级缠绕线圈,包括:
具有纵向轴线的初级缠绕线圈,所述初级缠绕线圈由围绕所述初级缠绕线圈的所述纵向轴线盘绕的柔性金属导线形成,所述初级缠绕线圈沿着所述纵向轴线伸长并且具有非圆形剖面形状,所述非圆形剖面形状沿着所述纵向轴线进动以形成重复扭绞线圈模式;以及
所述初级缠绕线圈形成为具有从由圆柱形、圆锥形、球形和类球形形状及其组合组成的群组中选择的次级形状。
11.根据权利要求10所述的次级缠绕线圈,其中所述单个柔性金属盘绕导线具有双螺旋的外部形状。
12.根据权利要求10所述的次级缠绕线圈,其中从由椭圆、具有圆角形状的长方形和大致三角形组成的群组中选择所述非圆形剖面形状。
13.根据权利要求10所述的次级缠绕线圈,其中所述非圆形剖面形状沿着横穿所述纵向轴线的至少一个横向轴线伸长,并且其中所述至少一个横向轴线沿着所述纵向轴线进动。
14.根据权利要求13所述的次级缠绕线圈,其中所述非圆形剖面形状沿着与所述纵向轴线成角度的一个横向轴线伸长。
15.根据权利要求13所述的次级缠绕线圈,其中所述非圆形剖面形状沿着与所述纵向轴线成角度的第一横向轴线和第二横向轴线伸长。
16.根据权利要求10所述的次级缠绕线圈,其中所述初级缠绕线圈具有沿着所述初级缠绕线圈的纵向轴线的内部空间,且还包括沿着所述初级缠绕线圈的所述纵向轴线穿过所述内部空间延伸的轴向材料股线。
17.根据权利要求10所述的次级缠绕线圈,其中所述初级缠绕线圈在所述初级缠绕线圈的不同平面上具有可变的弯曲力矩,使得最小弯曲力的平面沿着所述初级缠绕线圈的长度变化。
18.一种形成具有扭绞线圈模式的柔性金属导线线圈的方法,该方法包括:
提供具有为非圆形剖面的外部表面的心轴,所述非圆形剖面的轴线沿着所述心轴以预定纵向扭绞模式进动;以及
围绕所述心轴的长度缠绕柔性线圈导线以形成初级缠绕线圈,该初级缠绕线圈具有对应于所述心轴的所述外部表面的形状的扭绞形状。
19.根据权利要求18所述的方法,还包括下述步骤:将所述初级缠绕线圈形成为具有从由圆柱形、圆锥形、球形和类球形形状组成的群组中选择的次级形状。
20.根据权利要求18所述的方法,其中所述初级缠绕线圈具有沿着所述初级缠绕线圈的纵向轴线的内部空间,并且该方法还包括下述步骤:将材料股线沿着所述初级缠绕线圈的所述纵向轴线插入所述初级缠绕线圈的所述内部空间。
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-
2008
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- 2008-08-18 EP EP08827783.5A patent/EP2182854B1/en active Active
- 2008-08-18 CN CN2008801118910A patent/CN101959464B/zh active Active
- 2008-08-18 JP JP2010521971A patent/JP5580737B2/ja active Active
- 2008-08-18 CA CA2696629A patent/CA2696629C/en not_active Expired - Fee Related
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EP2182854A4 (en) | 2015-07-08 |
US20090069836A1 (en) | 2009-03-12 |
JP5860499B2 (ja) | 2016-02-16 |
JP5580737B2 (ja) | 2014-08-27 |
ES2773758T3 (es) | 2020-07-14 |
JP2010536491A (ja) | 2010-12-02 |
EP2182854A2 (en) | 2010-05-12 |
WO2009026253A3 (en) | 2009-05-22 |
WO2009026253A2 (en) | 2009-02-26 |
EP2182854B1 (en) | 2019-12-11 |
CA2696629C (en) | 2016-01-19 |
US8870908B2 (en) | 2014-10-28 |
CA2696629A1 (en) | 2009-02-26 |
JP2014208025A (ja) | 2014-11-06 |
CN101959464B (zh) | 2012-07-04 |
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