CN101969891B - 不透射线的超弹性血管内支架 - Google Patents
不透射线的超弹性血管内支架 Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
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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
- A61B17/12099—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder
- A61B17/12109—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel
- A61B17/12113—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel within an aneurysm
- A61B17/12118—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel within an aneurysm for positioning in conjunction with a stent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
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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
- A61B2017/00526—Methods of manufacturing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
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- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
- A61F2250/0039—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in diameter
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- A—HUMAN NECESSITIES
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- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0096—Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers
- A61F2250/0098—Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers radio-opaque, e.g. radio-opaque markers
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T29/00—Metal working
- Y10T29/49—Method of mechanical manufacture
- Y10T29/4998—Combined manufacture including applying or shaping of fluent material
Abstract
血管内支架由复合丝形成,所述复合丝包括不透射线金属的内部核心(12)、围绕内部核心同轴设置的聚合物层(16)和围绕聚合物层同轴设置的外部金属层(18)。中间聚合物作为内部核心和外部护套之间的屏障材料,以使内部核心与外部护套可以由不同的金属层制成,并且中间聚合物层会防止内部核心与外围金属层之间的电反应。血管内支架(20)具有向外径向张开的端部(22、24),以防止当支架被放置在患者脉管系统内的期望位置时支架的端部径向和纵向向内变形。
Description
技术领域
本发明一般性地涉及用于介入治疗处理或血管手术的可植入血管闭塞装置,并且更具体地涉及由具有增强的不透射线性和增强的抗腐蚀性的复合丝(composite wire)所形成的不透射线的超弹性血管内支架。该血管内支架具有超弹性或形状记忆特性以及用于荧光透视下视觉检查的改善的不透射线特性,并且支架的端部向外径向张开以防止当支架被拉伸或放置在患者脉管系统的所需位置中时支架的端部径向和纵向向内变形。
背景技术
血管闭塞装置是一般经由导管被放置在人体的脉管系统内的治疗装置,其或者通过形成栓塞物以阻挡血液流经形成该部分脉管系统的血管,或者在源自血管的动脉瘤内形成这样的栓塞物。血管闭塞装置可以采取多种构造,并且通常由在展开构造下比其在放置之前在递送导管内时更大的一个或更多个元件形成。一种广泛使用的血管闭塞装置是具有可以被形成为接合血管壁的尺寸的展开构造的螺旋状丝线圈。
该血管闭塞装置——其可以具有丝线圈的初级形状,然后可以被形成为更复杂的次级形状——可以以这样的方式被制造:它们将以线性形状穿过导管的空腔,并在被展开到感兴趣的区域例如动脉瘤内后呈现如最初被形成的复杂形状。已经发展了将该装置从推动器中释放出来的多种分离机构,并且它们在本领域内是公知的。
例如,为了治疗小直径脉管区域如脑内的小动脉或静脉,以及为了治疗动脉瘤及类似物,使用由直径非常小的丝形成的微线圈以限制、加固或者闭塞这些小直径的脉管区域。已经建议了用于这些微线圈的多种材料,包括镍-钛合金、铜、不锈钢、铂、钨、各种塑料或类似物,其中每个在各种应用中都提供某些益处。镍-钛合金对于这种微线圈的制造是尤其有利的,因为它们可以具有超弹性或形状记忆特性,并且因此可以被制造为容易地装配进导管的线性部分,而当展开时获得它们最初被形成的更复杂的形状。然而,镍-钛合金丝在小直径时也不是不透射线的,并且单条镍-钛丝将需要大约0.012英寸的直径从而即使轻微地不透射线。但是,单条镍-钛丝的这样的厚度将不幸地也是相对刚性的并可能造成放置位置的创伤,尤其是在用于治疗小直径脉管的脆弱和已经损伤的区域的情况下,所述区域例如诸如脑内的动脉内的动脉瘤或静脉。
支架的一种已知类型包括由金属外部构件形成的金属细丝材料和由不同于外部构件的金属形成的内部核心。支架的另一类型由多种细丝形成,其中每个都是复合物,包括由不透射线的和相对易延展的材料例如允许支架体内成像的钽或铂形成的中间核心,以及由相对有弹性的材料例如钴/铬基合金形成的外壳。当核心和壳材料在接近时由于形成金属间化合物的趋势会不相容时,钽、铌或铂中间屏障层可以被设置在壳和核心之间。不透射线的壳可以环绕核心,或者为了提高相容性,生物相容性覆盖层例如钽、铂、铱、不锈钢、铌和钛中的一种或更多种可以环绕壳。
已知细长丝构件形式的另一类内镜置管术包括中心圆柱形或管状核心和外部管状护套。中间管状层可以被设置在内部管状层和外部管状层之间。该管可以包括由一种材料形成的外部层和内部层,所述一种材料例如钴、碳、锰、硅、磷、硫、铬、镍、钼、钛、铁、它们的合金和它们的组合;以及由另一种材料形成的外部层和内部层之间的中间层,所述另一种材料例如金、铂、钽、铱、钨和它们的合金以及它们的组合。
支架预制件的另一种类型包括具有实心截面的形状记忆合金的细长金属核心,以及由生物相容性聚合物例如热收缩性聚合材料或聚合带形成的中空外部护套以防止核心直接接触体腔。在支架预制件的另一种类型中,光滑衬垫中间衬套被设置在核心和外部护套之间。
已知支架的另一种类型由多种编结或编织的丝绳制造,该丝绳由材料例如不锈钢、钨、钛、镍钛合金、金或银制成,其外侧涂布有生物相容性氟聚合物。
虽然镍钛丝例如镍钛金属互化物丝具有在血管闭塞装置和支架中有用的重要的形状记忆和超弹性特性,但是这种材料不是非常不透射线的,因此期望使用在荧光透视下可视的更加不透射线的材料。更加不透射线的材料一般不具有适合于在血管闭塞装置和支架中成型的形状记忆和超弹性特性,并且组合这些不透射线的材料与镍钛丝例如镍钛金属互化物丝一般易于电蚀,导致较大的丝或较大的装配系统的故障或危害。还发现当血管内支架被纵向拉伸时,支架将在直径上自然收缩,但不会均一地收缩,因为支架端部的直径一般将收缩得比支架中心主体部分的直径收缩的程度高,导致被称为“鱼嘴”的支架状态。
因此需要提供由这样的结构元件制成的血管内支架,该结构元件提供形状记忆合金例如镍钛合金的优点,并且包含不透射线的材料,以使血管内支架在荧光透视下可视,并且在装置使用期间不受到电蚀。还需要提供这样的血管内支架,当该支架被拉伸或被设置在患者脉管系统内的期望位置时,其将抵抗支架端部的径向和纵向向内变形。本发明满足这些和其它需求。
发明内容
简要并概括地,本发明提供大致管状的血管内支架,所述支架具有:在支架的相对的第一端部和第二端部处的多个端部圈部分,以及由多个端部圈部分之间的多个中间环绕圈(intermediate circumferentialloop)形成的中间管状主体部分。中间管状主体部分具有第一直径、扩大的第一端部和扩大的相对的第二端部,并且扩大的第一端部和第二端部具有大于中间管状主体部分的第一直径的第二直径。在一个目前优选的方面,多个端部圈部分相对于支架的中间管状主体部分径向向外张开。在另一优选的方面,多个端部圈部分和中间管状主体部分的多个中间环绕圈由单根呈螺旋状缠绕的复合丝形成。该复合丝具有被相互紧邻放置的第一自由端部和第二自由端部,以及短部分的热收缩管用于将第一自由端部和第二自由端部捕捉到一起以防止复合丝的自由端部延伸远离支架的主体。血管内支架在被拉伸时呈现出线性形状,端部不收缩为比支架中心主体的直径小的直径。
在另一目前优选的方面,复合丝可以被制成圆柱形丝,并且包括:细长内部核心,其具有选定的长度并且由不透射线的金属形成;中间聚合物层,其紧邻并且环绕内部核心被同轴设置;以及外部金属层,其紧邻并且环绕聚合物层被同轴设置。不透射线的金属可以选自铂、钽、金和它们的组合,且内部核心典型为圆柱形——虽然其它形状可能适合于形成内部核心。在一个优选的方面,内部核心沿着复合丝的纵轴被设置在中心。
在另一优选的方面,聚合物层可由选自聚四氟乙烯、聚对二甲苯、氟取代的聚对二甲苯和它们的组合的聚合物形成,而外部金属层可由超弹性合金例如诸如镍钛金属互化物形成。在另一方面,内部核心和外部护套可以由不同的金属制成。
在另一方面,本发明提供圆柱形心轴,其包含:圆柱形主体,其具有第一端部和相对的第二端部以及纵轴;四个成直角设置的销的第一设置(第一销设置),其在圆柱形主体的第一端部处从圆柱形主体延伸;以及四个成直角设置的销的第二设置(第二销设置),其在圆柱形主体的第二端部处从圆柱形主体延伸。第一圆锥形端部帽被装配到圆柱形主体的第一端部;且第二圆锥形端部帽被装配到圆柱形主体的第二端部。在一个目前优选的方面,第一圆锥形端部帽和第二圆锥形端部帽具有在圆柱形主体的第一端部和第二端部处形成圆锥角的圆锥形渐缩的表面,并且在另一方面,圆锥角相对于圆柱形主体的纵轴为大约30°。
在另一目前优选的方面,本发明提供用于形成血管内支架的方法,其包含下列步骤:围绕在心轴的第一端部处心轴的第一销设置的第一销缠绕单条复合丝,以在支架的第一端部处形成第一端部圈部分,并且此后过渡以形成中间环绕圈;围绕在圆柱形心轴的第二端部处的第二销设置的第一销缠绕复合丝,以在支架的第二端部处形成第一端部圈部分,并且此后过渡以形成中间环绕圈;以及重复这些步骤以继续相继形成在心轴的相对的第一端部和第二端部处的多个端部圈部分之间的多个中间环绕圈。
本发明的这些和其它方面及优点将从下面的详细描述和附图中变得显而易见,所述详细描述和附图以举例方式说明本发明的特征。
附图说明
图1为根据本发明的复合丝的选定长度的透视图。
图2为沿着图1的线2-2所做的复合丝的横截面图。
图3为根据本发明由复合丝形成的不透射线的超弹性血管内支架的俯视图。
图4为图3的不透射线的超弹性血管内支架的侧视图。
图5为图3的不透射线的超弹性血管内支架的端视图。
图6为缠绕图3的不透射线的超弹性血管内支架的心轴的侧视图。
具体实施方式
如为了说明的目的而不是以限制方式而提供的附图所示,本发明具体体现为在图3-图6中示出的不透射线的超弹性血管内支架8,其由用于形成脉管介入装置例如诸如血管内支架、栓塞线圈和导丝的复合丝形成。参照图1和图2,复合丝10包括具有选定长度和由不透射线的金属形成的细长内部核心12,所述金属例如诸如但不限于铂、钽、金或它们的组合。虽然其它形状可以用于形成内部核心,但内部核心优选圆柱形构造;并且虽然内部核心可以可替代地从复合丝的中心纵轴移位,但内部核心优选沿着复合丝的纵轴14被设置在中心。
紧邻并且环绕内部核心的是优选绕内部核心同轴设置的中间聚合物层16。中间聚合物层由薄的连续聚合材料层形成,该材料例如诸如但不限于:聚四氟乙烯(PTFE)、聚对二甲苯(帕利灵)、或其耐高温衍生物例如氟取代的聚对二甲苯(帕利灵HT)或它们的组合。
紧邻并且环绕中间聚合物层的是优选绕中间聚合物层同轴设置的外部金属层18。在一个目前优选的方面,内部核心和外部金属层由不同的金属制成,并且外部金属层由超弹性合金例如诸如镍钛金属互化物形成——虽然其它金属材料可用于形成外部金属层。中间聚合物层有利地使金属核心和外部金属层隔离电蚀。
参照图3-图5,血管内支架以大体管状形状形成,其具有有第一直径D1的中间管状主体部分20、扩大的第一端部22和扩大的相对第二端部24。扩大的第一和第二端部优选具有大于中间管状主体部分的第一直径的第二直径D2。血管内支架现在优选由单条复合丝形成,该单条复合丝螺旋缠绕以形成在支架的相对第一和第二端部的多个端部圈部分28之间的多个中间环绕圈26。在另一目前优选的方面,多个端部圈部分30a、30b、30c、30d相对于支架的中间管状主体部分径向向外张开。当被拉伸时张开的血管内支架典型地呈现线性形状,而端部不收缩为直径小于支架的中心主体的直径。
参照图4,形成血管内支架的复合丝具有互相紧邻放置的第一自由端部32和第二自由端部34,并且在热收缩管36的短部分内被捕获在一起以防止复合丝的自由端部延伸远离支架的主体。
如图6所示,内部血管支架通过将一定长度的单条复合丝螺旋形地缠绕在圆柱形心轴40周围而形成,圆柱形心轴40具有在心轴第一端部46处从心轴延伸的四个成直角布置的销44a、44b、44c、44d(隐藏)的第一设置42,和在心轴第二端部52处从心轴延伸的四个成直角布置的销50a、50b、50c、50d(隐藏)的第二设置48。第一圆锥形端部帽54和第二圆锥形端部帽56被装配到心轴的第一和第二端部。第一和第二圆锥形端部帽在心轴的第一和第二端部处具有相对于心轴的纵轴62形成典型地为大约30°的角α的呈圆锥形渐缩的表面58、60,以提供用于成形血管内支架的向外张开的端部圈的径向向外张开表面。
根据本发明的方法,单条复合丝在心轴的第一端部处被缠绕在第一销设置的第一销44b周围,以在支架的第一端部处形成第一端部圈部分64,其后过渡形成中间环绕圈66。复合丝然后在心轴的第二端部处被缠绕在第二销设置的第一销50c周围,以在支架的第二端部处形成第一端部圈部分(隐藏),其后过渡形成另一中间环绕圈,等等,继续相继以这种方式其后在支架的相对的第一和第二端部处的多个端部圈部分之间形成多个中间环绕圈。如将会容易地显而易见地,缠绕可以在任何阶段开始,例如通过首先围绕圆柱形心轴缠绕以形成中间环绕圈,接下来围绕在心轴端部的销缠绕以形成端部圈部分,以这种方式相继进行。
本发明的不透射线的超弹性血管内支架被设计为在血管内展开而不需要球囊或其它膨胀元件,并且可以从引导管直接展开到被治疗的区域。本发明的血管内装置对于治疗包含动脉瘤及类似物的损伤的动脉尤其有用,尤其是通过使用用于闭塞动脉瘤的栓塞线圈或其它栓塞装置或药剂可治疗的那些。更具体地,本发明的血管内支架尤其好地适于与将这些栓塞线圈放置在动脉瘤内的导管类型一起应用,并且该装置可以用于加固动脉瘤的临近区域,同时允许通过支架内的间隙放置一个或更多个栓塞线圈,并且同时协助栓塞装置在动脉瘤圆顶内的保持。
根据前述会明显的是,虽然已经示出和描述了本发明的特定形式,但是可以不脱离本发明的精神和范围做出多种修改。因此,除了所附的权利要求,并不意图本发明受到限制。
Claims (6)
1.大致管状的血管内支架,其具有相对的扩大的第一端部和第二端部,所述血管内支架包含:
在所述支架的所述相对的扩大的第一端部和第二端部处的多个端部圈部分,以及由在所述多个端部圈部分之间的多个中间环绕圈形成的中间管状主体部分,所述中间管状主体部分具有第一直径,所述扩大的第一端部和第二端部具有大于所述中间管状主体部分的所述第一直径的第二直径,并且所述多个端部圈部分相对于所述支架的所述中间管状主体部分的纵轴以30°的角度向外径向张开,其中所述多个端部圈部分和所述中间管状主体部分的所述多个中间环绕圈由单条呈螺旋形缠绕的复合丝形成,所述复合丝包括:细长内部核心,其具有选定的长度并且由不透射线的金属形成;外部金属层,其沿着所述细长内部核心的长度围绕所述细长内部核心被同轴设置,其中所述外部金属层由镍钛合金形成,并且其中所述细长内部核心和外部金属层由不同的金属形成;以及连续中间聚合物层,其位于所述外部金属层和所述细长内部核心之间,所述连续中间聚合物层被配置为使所述细长内部核心和所述外部金属层与电蚀隔离,并且所述连续中间聚合物层由选自聚对二甲苯、氟取代的聚对二甲苯或它们的组合的聚合物形成,其中所述血管内支架在被拉伸时呈现线性形状,而所述第一端部和所述第二端部不收缩为直径小于所述支架的所述中间管状主体部分的直径,所述复合丝具有被相互紧邻放置在所述中间管状主体部分中的第一自由端部和第二自由端部,和热收缩管的短部分,所述热收缩管的短部分将所述第一自由端部和第二自由端部捕获到一起,形成在所述中间管状主体部分中的所述复合丝的所述第一自由端部和第二自由端部的接头,所述接头形成所述多个中间环绕圈中的一个的延续部分,从而防止所述复合丝的自由端部延伸远离所述支架的所述中间管状主体部分。
2.根据权利要求1所述的血管内支架,其中所述不透射线的金属选自铂、钽、金或它们的组合。
3.根据权利要求1所述的血管内支架,其中所述内部核心是圆柱形的。
4.根据权利要求1所述的血管内支架,其中所述内部核心沿着所述复合丝的纵轴被设置在中心。
5.根据权利要求1所述的血管内支架,其中所述外部金属层由超弹性合金形成。
6.根据权利要求1所述的血管内支架,其中所述复合丝被形成为圆柱形丝。
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- 2009-01-06 EP EP09700638.1A patent/EP2247268B1/en not_active Not-in-force
- 2009-01-06 JP JP2010541588A patent/JP5419893B2/ja not_active Expired - Fee Related
- 2009-01-06 CA CA2951303A patent/CA2951303A1/en not_active Abandoned
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- 2009-01-06 WO PCT/US2009/030217 patent/WO2009089216A2/en active Application Filing
- 2009-01-06 CN CN200980101793.3A patent/CN101969891B/zh not_active Expired - Fee Related
- 2009-01-06 WO PCT/US2009/030220 patent/WO2009089218A2/en active Application Filing
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2010
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2013
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Also Published As
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US8623071B2 (en) | 2014-01-07 |
CN101969891A (zh) | 2011-02-09 |
WO2009089218A3 (en) | 2009-10-29 |
US20140082924A1 (en) | 2014-03-27 |
US8597344B2 (en) | 2013-12-03 |
CA2711484A1 (en) | 2009-07-16 |
CA2951303A1 (en) | 2009-07-16 |
WO2009089216A3 (en) | 2009-10-29 |
US20100152837A1 (en) | 2010-06-17 |
JP5419893B2 (ja) | 2014-02-19 |
US20140058500A1 (en) | 2014-02-27 |
WO2009089216A2 (en) | 2009-07-16 |
WO2009089218A2 (en) | 2009-07-16 |
JP2011509124A (ja) | 2011-03-24 |
CA2711484C (en) | 2017-01-24 |
US20090177268A1 (en) | 2009-07-09 |
ES2585404T3 (es) | 2016-10-05 |
EP2247268B1 (en) | 2016-05-18 |
EP2247268A2 (en) | 2010-11-10 |
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