CN1905913A - 用于在身体介质流过的脉管中释放活性物质的植入物 - Google Patents

用于在身体介质流过的脉管中释放活性物质的植入物 Download PDF

Info

Publication number
CN1905913A
CN1905913A CN200580001686.5A CN200580001686A CN1905913A CN 1905913 A CN1905913 A CN 1905913A CN 200580001686 A CN200580001686 A CN 200580001686A CN 1905913 A CN1905913 A CN 1905913A
Authority
CN
China
Prior art keywords
implant
active substance
matrix
body medium
weight
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN200580001686.5A
Other languages
English (en)
Other versions
CN1905913B (zh
Inventor
E·弗拉赫
W·盖斯特特
G·科尔贝格
C·哈德
R·罗德
H·米勒
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biotronik AG
Original Assignee
Biotronik VI Patent AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biotronik VI Patent AG filed Critical Biotronik VI Patent AG
Priority claimed from PCT/EP2005/001167 external-priority patent/WO2005075005A1/de
Publication of CN1905913A publication Critical patent/CN1905913A/zh
Application granted granted Critical
Publication of CN1905913B publication Critical patent/CN1905913B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02Inorganic materials
    • A61L31/022Metals or alloys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2210/00Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067Means for introducing or releasing pharmaceutical products into the body
    • A61F2250/0068Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • A61L2300/604Biodegradation

Abstract

本发明的任务是提供用于在身体介质流过的脉管中释放活性物质的植入物。该任务通过根据本发明的用于在身体介质流过的脉管中释放活性物质的植入物而完成,其中该植入物包含有基体,该基体由作为待释放的活性物质的载体的可生物降解性材料组成,并且其在内部和外部被身体介质环绕流过。

Description

用于在身体介质 流过的脉管中释放活性物质的植入物
本发明涉及用于在身体介质(K_rpermedium)流过的脉管中释放活性物质的植入物以及这类植入物的应用。
几千年来,人们一直尝试着通过靶向给予药学上有效的物质,来加速病理学过程和状态的治疗进程,或者来缓解与疾病相关的症状。除了选择和寻找合适的活性物质之外,还有一个问题在于,将活性物质在所希望的治疗位点处提供使用。为了保持小的通常与给药伴随出现的副作用,应当将活性物质的释放仅限制在治疗的位点上。此外,为了优化作用的效果,常常必需尽可能地遵守必要的剂量,即在治疗位点处于可预先规定的时间内将活性物质浓度保持在一定的范围界限之内。通常地,活性物质是经口服、皮下、静脉内或直肠施用的。正是在局部疾病如肿瘤的情况下,常规的全身性药物给予导致显著的并发症。
因此,几年来,作出了更多的努力将活性物质更为定向地引入待治疗的患者的体内。对于从植入物开始的仅仅在局部的治疗,即活性物质的洗脱基本上只在直接包围植入物的组织之中,已经形成了术语“局部药物递送(Local Drug Delivery,LDD)”。据此,治疗位点,即活性物质应当在此处发挥其药理学作用的位点,就直接接近于植入位点。
对于LDD-系统来说,一个重要的应用范围例如在于改善永久性植入物的生物相容性,例如移植片固定模、心起搏器或矫形外科假肢。在这里,特别是应当减少或避免由于植入物的存在和由于植入而引起的并发症。
一种与具有上述含义的LDD-系统不同的活性物质给予方式(本发明也归入这一类)基于这样的一种想法,即植入位点和治疗位点在空间上相互之间分得更开。换而言之,在植入物上释放的活性物质应当不是直接(局部)起作用,而是在身体中转运之后才在与植入点在空间上分离的组织区域之中发挥其作用。对于这种类型的区域性活性物质给予方式,我们在下文中使用术语“区域性药物递送(Regional DrugDelivery,或者简称为RDD)”。
对于确定的疾病形成因素,例如限于局部的肿瘤,通过待治疗的组织的脉管系统而提供活性物质的给予。对此必需的是,将植入物引入位于治疗位点前的脉管中。在现有技术中的方案例如是,将含有活性物质的聚合物基质注射入脉管中。在此,该基质是这样形成的,即在注射之后直接转变成坚韧的薄膜,所述薄膜粘附在脉管壁上。这种含有活性物质的薄膜逐渐地分解,其中释放出活性物质。然而,在实践中非常困难的是,达到如此点精确地注射入所涉及的脉管中。此外,无论如何都会引起血管壁的损伤,这例如可通过血栓形成而引起进一步的并发症。最后,剂量还取决于薄膜的厚度,即只是难以能够预测事实上存在哪种释放特征。
因此,本发明的任务在于提供用于在身体介质流过的脉管中释放活性物质的植入物。
该任务通过具有权利要求1中所述特征的植入物而完成。用于在身体介质流过的脉管中释放活性物质的植入物的特征在于,该植入物包含有基体,该基体由作为待释放的活性物质的载体的可生物降解性材料组成,并且其被身体介质由内部和/或外部环绕流过。换而言之,身体介质,特别是血液,在植入了植入物之后最大程度上无阻碍地通过或围绕该植入物流动。该植入物的基体用作活性物质的载体,该活性物质至少最大程度地洗脱入从旁边流过的身体介质中并被带至排列在其后的治疗位点处。该植入物的基体会随着时间而分解。
因此,该植入物特别适合于区域性活性物质给予(RDD)的目的,尤其是治疗肿瘤。因而,分别要求保护该植入物的这些用途。
在本发明中,脉管是指动脉和静脉血管的总和,包括毛细血管床的管(就广义而言,也包括淋巴管),它们与心脏一起形成一个功能单位。为此形成根据本发明的植入物以便在流过脉管的身体介质中释放活性物质。以这种方式,活性物质从释放位点到达对于其来说真正的、位于下游的作用位点。因此,如此形成植入物,即活性物质主要(优选所用活性物质的至少80重量%)在脉管的内部释放并被身体介质带走。要避免向脉管壁的方向释放。因此,优选地,在根据本发明的植入物中,在植入后与脉管壁保持接触的区域不用作活性物质的载体。如果植入物例如具有管状的轮廓,该轮廓在植入后以其外壁支撑在脉管上,那么在外壁上就不施加活性物质。
在本发明中,基体是指植入物的结构,其在生物降解开始之前保证植入物的机械完整性,和用作待释放的活性物质或包含活性物质的基质的载体。
如果身体介质只是流过基体,那么基体优选地以管状的、在其末端形成开口的基体形式,其(在被植入的状态下)以它的外侧贴在脉管壁上。由于依据脉管横截面而相适应的成型,大大地抑制了或至少减少了身体介质中的湍流,从而这种植入物变化形式特别适合于具有高体积流量的身体介质的脉管。
根据本发明的植入物的第二种变化形式,身体介质在内部或者外部通过或围绕基体流动。为此可以将基体设计为空心体(Hohlk_rper),其具有在流动方向上对准的入口和出口。这些在植入之后身体介质即刻或短时间内进入的空心体可以被构造成特别是管状、圆柱状或球状。为了确保植入物在身体中的相对位置,存在有至少在很大程度上可生物降解的锚定元件,其从基体开始伸展至脉管壁并在那里帮助进行锚定。
这些锚定元件例如可以具有锯齿形、钩形或鳞片状的轮廓。这些锚定元件是如此设计的,即其至少在90重量%,特别是95重量%的活性物质的释放时间内确保植入物的锚定。使用锚定元件减少了植入物和脉管壁之间的接触面,从而同样也限制了可能的内皮化(Endotheliasierung)的范围。锚定元件的具体布置尤其取决于植入位点处主要的流动关系、活性物质的释放特性和基体的降解特征,从而对于每一种应用必须进行植入物的单独调整。在此,技术人员将能够根据下面几方面的一般知识来实现这些目标:
-身体脉管的流变学,
-通过物质改性或合金选择(包括其加工和涂层)的可生物降解材料的降解特性的影响,以及
-取决于其改性或结合入基质的活性物质的释放特性的影响。
出于生产技术的原因,锚定元件优选地由本身可生物降解的材料形成,并与基体连接成一体。
根据本发明的植入物的第三种变化形式规定,基体只被身体介质环绕流过。换而言之,该基体显示出封闭的结构,在该结构中只有基体的外壁与身体介质接触。该基体或者紧凑地构造,或者在空心基体的情况下存在的基体内壁首先需经生物降解才可到达。可以考虑的特别是,具有网状的、锥形的或薄片状的基本模式的基体。这些植入物变化形式的基体同样也可以借助于前述的锚定元件而固定在脉管中。
前述封闭的结构的一个优选变化形式规定,基体从外至内多层地构造。在层上或者层之间存在有待释放的活性物质。在身体中,外层首先分解,并释放出存在于其下的活性物质。然后,下一层分解,并释放出存在于此层下的活性物质,依此类推。
根据本发明的一个优选实施方案,植入物的基体至少在部分区域由可生物降解的镁-、铁-或钨合金组成。在这些合金中,以合金的50重量%,尤其是70重量%,特别优选80重量%的含量各自含有给出名称的元素。此外,WE型的镁合金是特别优选的,特别是WE43,在其中向合金中添加了稀土金属和钇。这些所述的合金使之能够在技术上很好地进行加工,具有特别适合于实现本发明的植入物的机械方面的材料性能,和显示出在活的生物体中的有利的分解特性。此外,正是在镁合金的情况下,当基体生物降解时对于包围基体的组织还似乎出现了积极的生理学作用。
具有含量为1-30重量%的锂的镁合金是进一步优选的,因为其具有所期望的高的生物相容性。此外,具有含量为0.1重量%-10重量%的铝的镁合金以及具有含量为0.01重量%-2重量%的锆的镁合金由于其加工技术方面的、机械方面的和分解相关的性能而是特别优选的。这些所述的镁合金的成分,即稀土金属(E)、钇(W)、锂(L)、铝(A)和锆(K),可以以任意的组合成为合金的成分,其中括号中的标准化的合金成分缩写符号是根据ASTM而给出的。因此,例如可以使用下列类型的合金组成:LWE、AL、LAE和LE,其中字母顺序还可以根据所使用的合金组成而改变。因而,镁合金优选含有选自稀土金属、钇、锂、铝和锆的一种或多种合金成分。
进一步优选地,如此构造植入物的基体,即其能够具有第一种非膨胀的状态和第二种膨胀的状态。为了实现这样的结构,可以采用许多已知的移植片固定模设计。但是,需要说明的是,与移植片固定模相反,这种变化形式的根据本发明的植入物对于脉管壁一点也不施加支撑功能或者应当一点也不施加支撑功能。只是必须保证植入物锚定在脉管中,即不被持续不断的身体介质流拖走。因此,采用这种设计存在有比具有支撑功能的植入物更大的自由度。例如,活性物质是覆盖基体的涂层的成分,从而应当尽可能大面积地在面向身体介质的基体部分区域上分布,并使之覆盖有活性物质。只要活性物质的洗脱不受妨碍,内皮化即植入物的入内生长(Einwachsen)是可以忍受的。可选地,必须例如通过植入物内腔面的特定表面结构或者具有抵抗入内生长过程的物质的涂层而反向控制入内生长。
优选地,根据本发明的用于在身体介质流过的脉管中释放活性物质的植入物如下获得:
-基体在面向脉管的一侧的至少区域性地具有含有活性物质的涂层,
-基体具有一个或多个含有活性物质的空穴(Kavit_ten),和/或
-基体具有一个或多个含有活性物质的空心体。
因此,第一种变化形式表现出,基体至少部分地涂覆有活性物质。在此,涂层可以由活性物质本身组成,也可以由含有活性物质的、可生物降解的基质组成。例如可以考虑,将活性物质包埋入由透明质酸或其衍生物构成的基质中。基质的选择,还有活性物质的施用形式强烈地影响着活性物质的体内释放行为。释放行为的优化可以根据非常不同的、影响释放行为的大小仅针对具体体系来完成。需要说明的是,优选地如此预先确定涂层的位点,即将活性物质几近完全地在流过脉管的身体介质中释放,而不是向紧贴着的脉管壁的方向上释放。
根据第二种变化形式,含有活性物质的空穴位于基体之中。在本发明中,空穴是指基体中的凹坑、裂缝或钻孔,其不是完全被基体包围,即至少在一侧是可通达的。活性物质或者以纯的形式存在,或者以基质内结合的形式而存在于空穴的内部。这类空穴的产生是例如从移植片固定模领域充分已知的,并可以例如借助于激光方法来实施。只是确保通过或围绕本发明植入物流动的身体介质逐渐地从空穴中溶解出活性物质。这一过程随着进行中的基体降解而加快。与涂层不同,通常预期具有延缓的释放。
最后,根据本发明的植入物的另一种变化形式规定,基体含有一个或多个空心体,在其中引入了活性物质。在此活性物质还可以作为纯物质而存在,或者包埋在基质中。在本发明中,空腔是被基体完全包围的空间,在其中事先引入了活性物质。首先通过基体的逐渐降解,活性物质才是可通达的和能够溶解在从旁边流过的身体介质中。与此相应地,本变化形式通常表现出相对于两种前述的变化形式来说延缓时间最长的活性物质释放。例如,一种可考虑的变化形式规定,形成由空心的金属丝构成的基体,该金属丝的内部用活性物质填充。
为了影响单个活性物质的释放特性曲线或者为了以可预先给定的时间顺序控制不同活性物质的释放,所有三种所述变化形式可以以任意方式组合。
可以用依靠已知技术的植入系统毫无问题地将植入物引入身体介质流过的脉管中。因此,可以预先规定,将植入物装配在气囊导管系统的气囊上。然后,将导管以已知的方式导向植入位点。随后,将载有植入物的气囊膨胀并放置下植入物。在气囊缩小后,将导管抽回,植入物以固定的位置保留在所希望的位点处直至其分解。为了引入根据本发明的植入物的目的,如果植入物在载体系统上可以采用第三种的、绉缩的状态,则可以是有利的。
为此,可选择的植入系统可以由多根,特别是三根或四根,伸长的、在局部热影响下膨胀的镍钛诺金属丝(Nitinoldr_hte)组成。将所述镍钛诺金属丝如此布置在植入物上,即通过这些镍钛诺金属丝的膨胀能够迫使植入物锚定在植入位点处。因此,这种植入系统特别适合于具有前述锚定元件的植入物。
在下文中,将借助于实施例及附属的附图来进一步说明本发明。
附图为:
图1a-1c:根据本发明的用于在身体介质流过的脉管中释放活性物质的植入物的示意性描绘,和
图2a-2c:依照图1a、1b或1c的不同变化形式植入物的部分区域的示意性断面。
图1a-1c以非常示意性的方式显示了植入物10、30、40,它们适合于在身体介质流过的脉管中释放活性物质。
图1a引用了第一种变化形式的本发明植入物10。植入物10由管状的基体12组成,该基体在其端面14和16上是开放的并可以让身体介质流过。流过植入物10的基体12的身体介质(特别是血液)的流动方向由两个箭头18、20示出。
图1b显示了第二种变化形式的合适的植入物30。将基体32设计为空心体,但其轮廓并不适应于植入物30所锚定在其中的脉管。在流动方向(同样也用箭头18、20标示)上,基体具有入口和出口34、36。与图1a的变化形式不同,身体介质不仅在内部而且在外部通过或围绕基体32流动。为了确保植入物32在身体中的相对长度,在基体上形成锚定元件38,其在植入后支撑在脉管壁上并依靠其造型而提供附着。在具体情况下,锚定元件38构造成锯齿的形状,但是也可以具有其他的轮廓。此外,锚定元件38至少在很大程度上由可生物降解的材料组成。将锚定元件38设计成能够在90重量%,特别是95重量%的活性物质的释放时间内确保植入物30的锚定。锚定元件38的具体布置尤其取决于植入位点处存在的流动关系、活性物质的释放行为和基体32的降解特征,从而对于每一种应用必须进行植入物30的单独调整。出于生产技术的原因,锚定元件38优选地由与基体32一样的可生物降解的材料形成,并与基体32连接成一体。
图1c示意性地显示了第三种变化形式的本发明植入物40。根据这一变化形式,基体42构造为封闭的结构,即刚刚植入之后只有基体的外壁与身体介质接触。所描绘的基体42具有网状的结构,并借助于锚定元件48固定在脉管中。各个网线之间出现的自由空间50用含有活性物质的箔状基质覆盖。该基质例如可以通过将网状的基体42浸渍在含有基质的溶液中并随后干燥经润湿的基体42而进行涂覆。基体42以及该基质由可生物降解的材料形成。
图1a、1b和1c的基体12、32、42用作为一种、可选地多种在身体介质中释放的活性物质的载体。在活性物质释放期间或者至少在这之后,基体12、32、42最大程度地完全分解,即其至少最大程度地由可生物降解的材料组成。
作为用于基体12、32、42的可生物降解的材料,特别可以考虑元素镁、铁和钨的合金。在此,所述的合金元素各具有至少50重量%,优选多于70重量%,特别优选多于80重量%的含量。特别优选的是含有稀土金属和钇的镁合金,通常称为WE型的合金。关于WE型的合金,材料WE43经证明是特别适合的,即活性物质的生物降解受控地进行,在降解时释放的分解产物丝毫没有毒性作用或者最多只有低的毒性作用,和在加工材料时可以回溯到用于镁合金的传统加工技术。
含有含量为1-30重量%的锂的镁合金是进一步优选的,因为其具有所期望的高的生物相容性。此外,具有含量为0.1重量%-10重量%的铝的镁合金以及具有含量为0.01重量%-2重量%的锆的镁合金由于其加工技术方面的、机械方面的和分解相关的性能而是特别优选的。这些所述的镁合金的成分,即稀土金属(E)、钇(W)、锂(L)、铝(A)和锆(K),可以以任意的组合成为合金的成分,其中括号中的标准化的合金成分缩写符号是根据ASTM而给出的。因此,例如可以使用下列类型的合金组成:LWE、AL、LAE和LE,其中字母顺序还可以根据所使用的合金组成而改变。
植入物10的基体12在图1a中没有描绘出详细的结构。但是,基体12通常不作为完全封闭的管存在,而是由许多桩状的(strebenf_rmiger)或金属丝状的结构元件构成。所以,这样的构造是特别优选的,因为这样就可以非常容易地将植入物引入至植入位点处。因此,在相应地布置这些结构元件时,基体12具有第一种的、直径较小的、非膨胀的状态,和在植入位点处扩张之后表现出第二种膨胀的状态。不言而喻,在植入物10的非膨胀的状态下,将植入物引入至植入位点处是明显容易的。为此可以预先规定,将植入物装配在导管系统的气囊上。然后,将气囊导管引导入身体内并在所期望的位置通过气囊的膨胀而将植入物10膨胀开(完全类似于用同样的系统进行移植片固定模的扩张)。对于引入植入物10的目的,如果植入物10在载体系统上可以具有第三种的、绉缩的状态,则可以是有利的。此外,可以使用以机械性的牵拉装置或推动装置或者借助于热变形进行工作的植入系统。因此,例如可以计划有三根或四根伸长的、在局部热影响下膨胀的镍钛诺金属丝。将所述镍钛诺金属丝如此布置在植入物上,即通过这些镍钛诺金属丝的膨胀能够迫使植入物锚定在植入位点处。因此,这种植入系统特别适合于具有前述锚定元件38、48的植入物。
原则上,设计形成基体12的图1a中的植入物10的结构元件可以依据已知的移植片固定模设计。但是,需要保证,植入物10不施行支撑功能,即移植片固定模应当设计得非常柔软,以防止脉管损伤。该设计用于锚定在脉管中,并应当防止植入物10被身体介质带走。此外,活性物质的洗脱应当不会由于植入物10的向内生长入脉管壁中而受到阻碍。因此,为此目的可以调整该设计,例如通过在与脉管壁接触的植入物10的位置处用抗增殖性物质涂覆或进行表面改性。
图2a-2c以非常示意的方式显示了依照图1a-1c的植入物10、30、40的断面,更确切地说是各在这样的区域中的断面,即在该区域中基体12、32、42作为活性物质22或含有活性物质22的基质的载体。为了简便起见,下面仅涉及图1a的植入物10的变化形式。但是,所描述的措施可以毫不困难地转用至具有与之不同的造型的其他植入物变化形式上。
在图2a中,活性物质22作为涂层24涂覆在基体12上。合适地,涂层24存在于管状基体12的内侧,从而流动着的身体介质能够与活性物质22接触,和能够将活性物质22以溶解的形式洗脱入安排在之后的组织区域内。活性物质22可以以纯的形式,例如微晶或无定形产物,粘附在基体12上。但是也可以考虑将活性物质22包埋在基质中,以便使得能够例如更好地粘附在基体12上和/或影响活性物质22的释放。作为基质例如可以考虑可生物降解的聚合物,例如透明质酸及其衍生物。
在图2b中所描绘的第二种变化形式规定,在植入物10的基体12中引入空穴26,并用活性物质22或含有活性物质22的基质将其填充。这类的空穴26例如可以通过已知的激光方法产生。空穴26可以以裂缝、钻孔或其他几何形状的形式而实现。活性物质22可以例如通过下述过程而被确定地引入空穴26中,即浸渍在含有活性物质22的溶液中、干燥溶液和吹净存在于空穴26之外的活性物质沉积物。活性物质22被从旁边流过的身体介质慢慢地从空穴26中冲洗出来。同时,这一过程通过基体12的逐渐降解而得到加强。
最后,在图2c中所描绘的植入物10的第三种变化形式规定,基体12具有在其中引入了活性物质22的空腔28。在基体12的面向身体介质一侧分解之后,活性物质22才洗脱入身体介质中。这样的系统例如可以通过使用空心金属丝来实现,在该空心金属丝中通过毛细力而引入活性物质22的溶液。
不言而喻,可以改变用于控制活性物质22的释放能力的措施。为此可考虑,能够不仅将一种活性物质,而是将多种活性物质,而且在时间上相互关联地装入、释放。在此,一种或多种活性物质的释放取决于载体材料的选择、活性物质在基体上的几何状况(即涂层、空穴或空腔)、可能含有活性物质的基质的性质以及植入位点处的流变学和解剖学的现实情况。前述的本发明植入物的变化形式特别适合于区域性药物递送(RDD)的目的。

Claims (13)

1.用于在身体介质流过的脉管中释放活性物质(22)的植入物(10、30、40),其中所述植入物(10、30、40)包含基体(12、32、42),该基体由作为待释放的活性物质(22)的载体的可生物降解性材料组成,并且其在内部和/或外部被身体介质环绕流过。
2.权利要求1的植入物,其特征在于,所述基体(12、32)至少在部分区域由可生物降解的镁-、铁-或钨合金组成。
3.权利要求2的植入物,其特征在于,镁合金是WE型的合金。
4.权利要求3的植入物,其特征在于,镁合金是WE43型的合金。
5.权利要求2的植入物,其特征在于,镁合金含有含量为1-30重量%的锂。
6.权利要求2的植入物,其特征在于,镁合金含有含量为0.1重量%-10重量%的铝。
7.权利要求2的植入物,其特征在于,镁合金含有含量为0.01重量%-2重量%的锆。
8.权利要求2的植入物,其特征在于,镁合金含有选自稀土金属、钇、锂、铝和锆的一种或多种合金成分。
9.前述权利要求中任一项的植入物,其特征在于,如此构造植入物(10、30)的基体(12、32),即其可以采取第一种、非膨胀的状态和第二种、膨胀的状态。
10.前述权利要求中任一项的植入物,其特征在于,所述基体(12、32)
-在其面向脉管的一侧至少区域性地具有涂层(24),和/或
-具有一个或多个空穴(26),和/或
-具有一个或多个空心体(28),
它们含有活性物质(22)。
11.权利要求1的植入物,其特征在于,基体(12、32、42)是管状的、圆柱状的、球状的或网状的。
12.权利要求1-11中任一项的植入物用于区域性活性物质给药(区域性药物递送-RDD)的用途。
13.权利要求1-11中任一项的植入物用于肿瘤治疗的用途。
CN200580001686.5A 2004-02-06 2005-02-04 用于在身体介质流过的脉管中释放活性物质的植入物 Expired - Fee Related CN1905913B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE102004006745.7 2004-02-06
DE102004006745 2004-02-06
DE102004029611.1 2004-06-09
DE102004029611A DE102004029611A1 (de) 2004-02-06 2004-06-09 Implantat zur Freisetzung eines Wirkstoffs in ein von einem Körpermedium durchströmtes Gefäß
PCT/EP2005/001167 WO2005075005A1 (de) 2004-02-06 2005-02-04 IMPLANTAT ZUR FREISETZUNG EINES WIRKSTOFFS IN EIN VON EINEM KÖRPERMEDIUM DURCHSTRÖMTES GEFÄß

Publications (2)

Publication Number Publication Date
CN1905913A true CN1905913A (zh) 2007-01-31
CN1905913B CN1905913B (zh) 2010-10-06

Family

ID=34801879

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200580001686.5A Expired - Fee Related CN1905913B (zh) 2004-02-06 2005-02-04 用于在身体介质流过的脉管中释放活性物质的植入物

Country Status (4)

Country Link
US (1) US9095642B2 (zh)
JP (1) JP4769730B2 (zh)
CN (1) CN1905913B (zh)
DE (1) DE102004029611A1 (zh)

Families Citing this family (197)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7727221B2 (en) 2001-06-27 2010-06-01 Cardiac Pacemakers Inc. Method and device for electrochemical formation of therapeutic species in vivo
US20070084897A1 (en) 2003-05-20 2007-04-19 Shelton Frederick E Iv Articulating surgical stapling instrument incorporating a two-piece e-beam firing mechanism
US9060770B2 (en) 2003-05-20 2015-06-23 Ethicon Endo-Surgery, Inc. Robotically-driven surgical instrument with E-beam driver
US11890012B2 (en) 2004-07-28 2024-02-06 Cilag Gmbh International Staple cartridge comprising cartridge body and attached support
US11246590B2 (en) 2005-08-31 2022-02-15 Cilag Gmbh International Staple cartridge including staple drivers having different unfired heights
US7669746B2 (en) 2005-08-31 2010-03-02 Ethicon Endo-Surgery, Inc. Staple cartridges for forming staples having differing formed staple heights
US10159482B2 (en) 2005-08-31 2018-12-25 Ethicon Llc Fastener cartridge assembly comprising a fixed anvil and different staple heights
US7934630B2 (en) 2005-08-31 2011-05-03 Ethicon Endo-Surgery, Inc. Staple cartridges for forming staples having differing formed staple heights
US11484312B2 (en) 2005-08-31 2022-11-01 Cilag Gmbh International Staple cartridge comprising a staple driver arrangement
US20070106317A1 (en) 2005-11-09 2007-05-10 Shelton Frederick E Iv Hydraulically and electrically actuated articulation joints for surgical instruments
DE102005059606A1 (de) * 2005-12-12 2007-06-14 Raumedic Ag Wirkstoff-Applikationsvorrichtung
US8840660B2 (en) 2006-01-05 2014-09-23 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US20120292367A1 (en) 2006-01-31 2012-11-22 Ethicon Endo-Surgery, Inc. Robotically-controlled end effector
US8186555B2 (en) 2006-01-31 2012-05-29 Ethicon Endo-Surgery, Inc. Motor-driven surgical cutting and fastening instrument with mechanical closure system
US11793518B2 (en) 2006-01-31 2023-10-24 Cilag Gmbh International Powered surgical instruments with firing system lockout arrangements
US8820603B2 (en) 2006-01-31 2014-09-02 Ethicon Endo-Surgery, Inc. Accessing data stored in a memory of a surgical instrument
US7845537B2 (en) 2006-01-31 2010-12-07 Ethicon Endo-Surgery, Inc. Surgical instrument having recording capabilities
US8708213B2 (en) 2006-01-31 2014-04-29 Ethicon Endo-Surgery, Inc. Surgical instrument having a feedback system
US20110290856A1 (en) 2006-01-31 2011-12-01 Ethicon Endo-Surgery, Inc. Robotically-controlled surgical instrument with force-feedback capabilities
US8089029B2 (en) 2006-02-01 2012-01-03 Boston Scientific Scimed, Inc. Bioabsorbable metal medical device and method of manufacture
US8048150B2 (en) 2006-04-12 2011-11-01 Boston Scientific Scimed, Inc. Endoprosthesis having a fiber meshwork disposed thereon
US20070258903A1 (en) * 2006-05-02 2007-11-08 Kleiner Lothar W Methods, compositions and devices for treating lesioned sites using bioabsorbable carriers
CA2659761A1 (en) 2006-08-02 2008-02-07 Boston Scientific Scimed, Inc. Endoprosthesis with three-dimensional disintegration control
DE102006038241A1 (de) * 2006-08-07 2008-02-14 Biotronik Vi Patent Ag Stent mit einer genisteinhaltigen Beschichtung oder Kavitätenfüllung
ES2368125T3 (es) 2006-09-15 2011-11-14 Boston Scientific Scimed, Inc. Endoprótesis bioerosionable con capas inorgánicas bioestables.
US8808726B2 (en) 2006-09-15 2014-08-19 Boston Scientific Scimed. Inc. Bioerodible endoprostheses and methods of making the same
CA2663271A1 (en) 2006-09-15 2008-03-20 Boston Scientific Limited Bioerodible endoprostheses and methods of making the same
EP2959925B1 (en) 2006-09-15 2018-08-29 Boston Scientific Limited Medical devices and methods of making the same
WO2008036548A2 (en) 2006-09-18 2008-03-27 Boston Scientific Limited Endoprostheses
US10568652B2 (en) 2006-09-29 2020-02-25 Ethicon Llc Surgical staples having attached drivers of different heights and stapling instruments for deploying the same
DE112007003309B4 (de) * 2006-11-27 2013-02-07 Berthold Nies Knochenimplantat sowie Set zur Herstellung von Knochenimplantaten und seine Verwendung
EP2277563B1 (en) 2006-12-28 2014-06-25 Boston Scientific Limited Bioerodible endoprostheses and method of making the same
US8684253B2 (en) 2007-01-10 2014-04-01 Ethicon Endo-Surgery, Inc. Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor
US20080169332A1 (en) 2007-01-11 2008-07-17 Shelton Frederick E Surgical stapling device with a curved cutting member
US20220061862A1 (en) * 2007-01-11 2022-03-03 Cilag Gmbh International Surgical stapling device with a curved end effector
DE102007004589A1 (de) * 2007-01-30 2008-07-31 Orlowski, Michael, Dr. Bioresorbierbarer Metallstent mit kontrollierter Resorption
US11857181B2 (en) 2007-06-04 2024-01-02 Cilag Gmbh International Robotically-controlled shaft based rotary drive systems for surgical instruments
US8931682B2 (en) 2007-06-04 2015-01-13 Ethicon Endo-Surgery, Inc. Robotically-controlled shaft based rotary drive systems for surgical instruments
US11849941B2 (en) 2007-06-29 2023-12-26 Cilag Gmbh International Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis
US8052745B2 (en) 2007-09-13 2011-11-08 Boston Scientific Scimed, Inc. Endoprosthesis
US8636736B2 (en) 2008-02-14 2014-01-28 Ethicon Endo-Surgery, Inc. Motorized surgical cutting and fastening instrument
US7866527B2 (en) 2008-02-14 2011-01-11 Ethicon Endo-Surgery, Inc. Surgical stapling apparatus with interlockable firing system
JP5410110B2 (ja) 2008-02-14 2014-02-05 エシコン・エンド−サージェリィ・インコーポレイテッド Rf電極を有する外科用切断・固定器具
DE102008019748A1 (de) * 2008-04-18 2009-10-22 Gottfried Wilhelm Leibniz Universität Hannover Bioresorbierbares Material
US7998192B2 (en) 2008-05-09 2011-08-16 Boston Scientific Scimed, Inc. Endoprostheses
US8236046B2 (en) 2008-06-10 2012-08-07 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis
DE102008002395A1 (de) * 2008-06-12 2009-12-17 Biotronik Vi Patent Ag Wirkstoffbeladenes Implantat
US8202531B2 (en) * 2008-07-23 2012-06-19 Warsaw Orthopedic, Inc. Drug depots having one or more anchoring members
US7985252B2 (en) 2008-07-30 2011-07-26 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis
US9005230B2 (en) 2008-09-23 2015-04-14 Ethicon Endo-Surgery, Inc. Motorized surgical instrument
US8210411B2 (en) 2008-09-23 2012-07-03 Ethicon Endo-Surgery, Inc. Motor-driven surgical cutting instrument
US9386983B2 (en) 2008-09-23 2016-07-12 Ethicon Endo-Surgery, Llc Robotically-controlled motorized surgical instrument
US11648005B2 (en) 2008-09-23 2023-05-16 Cilag Gmbh International Robotically-controlled motorized surgical instrument with an end effector
US8382824B2 (en) 2008-10-03 2013-02-26 Boston Scientific Scimed, Inc. Medical implant having NANO-crystal grains with barrier layers of metal nitrides or fluorides
US8608045B2 (en) 2008-10-10 2013-12-17 Ethicon Endo-Sugery, Inc. Powered surgical cutting and stapling apparatus with manually retractable firing system
US8267992B2 (en) 2009-03-02 2012-09-18 Boston Scientific Scimed, Inc. Self-buffering medical implants
US8435281B2 (en) 2009-04-10 2013-05-07 Boston Scientific Scimed, Inc. Bioerodible, implantable medical devices incorporating supersaturated magnesium alloys
US8668732B2 (en) 2010-03-23 2014-03-11 Boston Scientific Scimed, Inc. Surface treated bioerodible metal endoprostheses
US11812965B2 (en) 2010-09-30 2023-11-14 Cilag Gmbh International Layer of material for a surgical end effector
US8777004B2 (en) 2010-09-30 2014-07-15 Ethicon Endo-Surgery, Inc. Compressible staple cartridge comprising alignment members
US9788834B2 (en) 2010-09-30 2017-10-17 Ethicon Llc Layer comprising deployable attachment members
US9320523B2 (en) 2012-03-28 2016-04-26 Ethicon Endo-Surgery, Llc Tissue thickness compensator comprising tissue ingrowth features
US9629814B2 (en) 2010-09-30 2017-04-25 Ethicon Endo-Surgery, Llc Tissue thickness compensator configured to redistribute compressive forces
US10945731B2 (en) 2010-09-30 2021-03-16 Ethicon Llc Tissue thickness compensator comprising controlled release and expansion
US11925354B2 (en) 2010-09-30 2024-03-12 Cilag Gmbh International Staple cartridge comprising staples positioned within a compressible portion thereof
US8695866B2 (en) 2010-10-01 2014-04-15 Ethicon Endo-Surgery, Inc. Surgical instrument having a power control circuit
BR112013027794B1 (pt) 2011-04-29 2020-12-15 Ethicon Endo-Surgery, Inc Conjunto de cartucho de grampos
US9072535B2 (en) 2011-05-27 2015-07-07 Ethicon Endo-Surgery, Inc. Surgical stapling instruments with rotatable staple deployment arrangements
RU2014143258A (ru) 2012-03-28 2016-05-20 Этикон Эндо-Серджери, Инк. Компенсатор толщины ткани, содержащий множество слоев
CN104334098B (zh) 2012-03-28 2017-03-22 伊西康内外科公司 包括限定低压强环境的胶囊剂的组织厚度补偿件
US9101358B2 (en) 2012-06-15 2015-08-11 Ethicon Endo-Surgery, Inc. Articulatable surgical instrument comprising a firing drive
US20140001231A1 (en) 2012-06-28 2014-01-02 Ethicon Endo-Surgery, Inc. Firing system lockout arrangements for surgical instruments
US9289256B2 (en) 2012-06-28 2016-03-22 Ethicon Endo-Surgery, Llc Surgical end effectors having angled tissue-contacting surfaces
US9408606B2 (en) 2012-06-28 2016-08-09 Ethicon Endo-Surgery, Llc Robotically powered surgical device with manually-actuatable reversing system
US9282974B2 (en) 2012-06-28 2016-03-15 Ethicon Endo-Surgery, Llc Empty clip cartridge lockout
US9700310B2 (en) 2013-08-23 2017-07-11 Ethicon Llc Firing member retraction devices for powered surgical instruments
JP6382235B2 (ja) 2013-03-01 2018-08-29 エシコン・エンド−サージェリィ・インコーポレイテッドEthicon Endo−Surgery,Inc. 信号通信用の導電路を備えた関節運動可能な外科用器具
BR112015026109B1 (pt) 2013-04-16 2022-02-22 Ethicon Endo-Surgery, Inc Instrumento cirúrgico
US10013049B2 (en) 2014-03-26 2018-07-03 Ethicon Llc Power management through sleep options of segmented circuit and wake up control
US20150297223A1 (en) 2014-04-16 2015-10-22 Ethicon Endo-Surgery, Inc. Fastener cartridges including extensions having different configurations
BR112016023807B1 (pt) 2014-04-16 2022-07-12 Ethicon Endo-Surgery, Llc Conjunto de cartucho de prendedores para uso com um instrumento cirúrgico
JP6636452B2 (ja) 2014-04-16 2020-01-29 エシコン エルエルシーEthicon LLC 異なる構成を有する延在部を含む締結具カートリッジ
CN104188741A (zh) * 2014-08-29 2014-12-10 东莞颠覆产品设计有限公司 一种植入体内的可降解接驳器
BR112017004361B1 (pt) 2014-09-05 2023-04-11 Ethicon Llc Sistema eletrônico para um instrumento cirúrgico
US10111679B2 (en) 2014-09-05 2018-10-30 Ethicon Llc Circuitry and sensors for powered medical device
US9924944B2 (en) 2014-10-16 2018-03-27 Ethicon Llc Staple cartridge comprising an adjunct material
US11141153B2 (en) 2014-10-29 2021-10-12 Cilag Gmbh International Staple cartridges comprising driver arrangements
BR112017012996B1 (pt) 2014-12-18 2022-11-08 Ethicon Llc Instrumento cirúrgico com uma bigorna que é seletivamente móvel sobre um eixo geométrico imóvel distinto em relação a um cartucho de grampos
US9943309B2 (en) 2014-12-18 2018-04-17 Ethicon Llc Surgical instruments with articulatable end effectors and movable firing beam support arrangements
US10085748B2 (en) 2014-12-18 2018-10-02 Ethicon Llc Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors
US9987000B2 (en) 2014-12-18 2018-06-05 Ethicon Llc Surgical instrument assembly comprising a flexible articulation system
US11154301B2 (en) 2015-02-27 2021-10-26 Cilag Gmbh International Modular stapling assembly
JP2020121162A (ja) 2015-03-06 2020-08-13 エシコン エルエルシーEthicon LLC 測定の安定性要素、クリープ要素、及び粘弾性要素を決定するためのセンサデータの時間依存性評価
US10213201B2 (en) 2015-03-31 2019-02-26 Ethicon Llc Stapling end effector configured to compensate for an uneven gap between a first jaw and a second jaw
US10105139B2 (en) 2015-09-23 2018-10-23 Ethicon Llc Surgical stapler having downstream current-based motor control
US10736633B2 (en) 2015-09-30 2020-08-11 Ethicon Llc Compressible adjunct with looping members
US11890015B2 (en) 2015-09-30 2024-02-06 Cilag Gmbh International Compressible adjunct with crossing spacer fibers
US10292704B2 (en) 2015-12-30 2019-05-21 Ethicon Llc Mechanisms for compensating for battery pack failure in powered surgical instruments
US11213293B2 (en) 2016-02-09 2022-01-04 Cilag Gmbh International Articulatable surgical instruments with single articulation link arrangements
JP6911054B2 (ja) 2016-02-09 2021-07-28 エシコン エルエルシーEthicon LLC 非対称の関節構成を備えた外科用器具
US10448948B2 (en) 2016-02-12 2019-10-22 Ethicon Llc Mechanisms for compensating for drivetrain failure in powered surgical instruments
US10426467B2 (en) 2016-04-15 2019-10-01 Ethicon Llc Surgical instrument with detection sensors
US10828028B2 (en) 2016-04-15 2020-11-10 Ethicon Llc Surgical instrument with multiple program responses during a firing motion
US11607239B2 (en) 2016-04-15 2023-03-21 Cilag Gmbh International Systems and methods for controlling a surgical stapling and cutting instrument
US10433840B2 (en) 2016-04-18 2019-10-08 Ethicon Llc Surgical instrument comprising a replaceable cartridge jaw
US20170296173A1 (en) 2016-04-18 2017-10-19 Ethicon Endo-Surgery, Llc Method for operating a surgical instrument
US10675025B2 (en) 2016-12-21 2020-06-09 Ethicon Llc Shaft assembly comprising separately actuatable and retractable systems
US20180168615A1 (en) 2016-12-21 2018-06-21 Ethicon Endo-Surgery, Llc Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument
US10675026B2 (en) 2016-12-21 2020-06-09 Ethicon Llc Methods of stapling tissue
JP7010956B2 (ja) 2016-12-21 2022-01-26 エシコン エルエルシー 組織をステープル留めする方法
US10524789B2 (en) 2016-12-21 2020-01-07 Ethicon Llc Laterally actuatable articulation lock arrangements for locking an end effector of a surgical instrument in an articulated configuration
US10779820B2 (en) 2017-06-20 2020-09-22 Ethicon Llc Systems and methods for controlling motor speed according to user input for a surgical instrument
US10307170B2 (en) 2017-06-20 2019-06-04 Ethicon Llc Method for closed loop control of motor velocity of a surgical stapling and cutting instrument
US11517325B2 (en) 2017-06-20 2022-12-06 Cilag Gmbh International Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval
US10881399B2 (en) 2017-06-20 2021-01-05 Ethicon Llc Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument
US11653914B2 (en) 2017-06-20 2023-05-23 Cilag Gmbh International Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector
US10993716B2 (en) 2017-06-27 2021-05-04 Ethicon Llc Surgical anvil arrangements
EP4070740A1 (en) 2017-06-28 2022-10-12 Cilag GmbH International Surgical instrument comprising selectively actuatable rotatable couplers
US11564686B2 (en) 2017-06-28 2023-01-31 Cilag Gmbh International Surgical shaft assemblies with flexible interfaces
US20190000461A1 (en) 2017-06-28 2019-01-03 Ethicon Llc Surgical cutting and fastening devices with pivotable anvil with a tissue locating arrangement in close proximity to an anvil pivot axis
US10765427B2 (en) 2017-06-28 2020-09-08 Ethicon Llc Method for articulating a surgical instrument
US11058424B2 (en) 2017-06-28 2021-07-13 Cilag Gmbh International Surgical instrument comprising an offset articulation joint
US10932772B2 (en) 2017-06-29 2021-03-02 Ethicon Llc Methods for closed loop velocity control for robotic surgical instrument
US10779826B2 (en) 2017-12-15 2020-09-22 Ethicon Llc Methods of operating surgical end effectors
US10682134B2 (en) 2017-12-21 2020-06-16 Ethicon Llc Continuous use self-propelled stapling instrument
US11696761B2 (en) 2019-03-25 2023-07-11 Cilag Gmbh International Firing drive arrangements for surgical systems
US11903581B2 (en) 2019-04-30 2024-02-20 Cilag Gmbh International Methods for stapling tissue using a surgical instrument
US11648009B2 (en) 2019-04-30 2023-05-16 Cilag Gmbh International Rotatable jaw tip for a surgical instrument
US11553971B2 (en) 2019-06-28 2023-01-17 Cilag Gmbh International Surgical RFID assemblies for display and communication
US11241235B2 (en) 2019-06-28 2022-02-08 Cilag Gmbh International Method of using multiple RFID chips with a surgical assembly
US11638587B2 (en) 2019-06-28 2023-05-02 Cilag Gmbh International RFID identification systems for surgical instruments
US11523822B2 (en) 2019-06-28 2022-12-13 Cilag Gmbh International Battery pack including a circuit interrupter
US11660163B2 (en) 2019-06-28 2023-05-30 Cilag Gmbh International Surgical system with RFID tags for updating motor assembly parameters
US11627959B2 (en) 2019-06-28 2023-04-18 Cilag Gmbh International Surgical instruments including manual and powered system lockouts
US11684434B2 (en) 2019-06-28 2023-06-27 Cilag Gmbh International Surgical RFID assemblies for instrument operational setting control
US11771419B2 (en) 2019-06-28 2023-10-03 Cilag Gmbh International Packaging for a replaceable component of a surgical stapling system
US11911032B2 (en) 2019-12-19 2024-02-27 Cilag Gmbh International Staple cartridge comprising a seating cam
US11844520B2 (en) 2019-12-19 2023-12-19 Cilag Gmbh International Staple cartridge comprising driver retention members
US11529139B2 (en) 2019-12-19 2022-12-20 Cilag Gmbh International Motor driven surgical instrument
US11529137B2 (en) 2019-12-19 2022-12-20 Cilag Gmbh International Staple cartridge comprising driver retention members
US11701111B2 (en) 2019-12-19 2023-07-18 Cilag Gmbh International Method for operating a surgical stapling instrument
US11504122B2 (en) 2019-12-19 2022-11-22 Cilag Gmbh International Surgical instrument comprising a nested firing member
US11576672B2 (en) 2019-12-19 2023-02-14 Cilag Gmbh International Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw
US11607219B2 (en) 2019-12-19 2023-03-21 Cilag Gmbh International Staple cartridge comprising a detachable tissue cutting knife
US11559304B2 (en) 2019-12-19 2023-01-24 Cilag Gmbh International Surgical instrument comprising a rapid closure mechanism
USD975850S1 (en) 2020-06-02 2023-01-17 Cilag Gmbh International Staple cartridge
USD974560S1 (en) 2020-06-02 2023-01-03 Cilag Gmbh International Staple cartridge
USD976401S1 (en) 2020-06-02 2023-01-24 Cilag Gmbh International Staple cartridge
USD975851S1 (en) 2020-06-02 2023-01-17 Cilag Gmbh International Staple cartridge
US20220031351A1 (en) 2020-07-28 2022-02-03 Cilag Gmbh International Surgical instruments with differential articulation joint arrangements for accommodating flexible actuators
USD1013170S1 (en) 2020-10-29 2024-01-30 Cilag Gmbh International Surgical instrument assembly
USD980425S1 (en) 2020-10-29 2023-03-07 Cilag Gmbh International Surgical instrument assembly
US11517390B2 (en) 2020-10-29 2022-12-06 Cilag Gmbh International Surgical instrument comprising a limited travel switch
US11779330B2 (en) 2020-10-29 2023-10-10 Cilag Gmbh International Surgical instrument comprising a jaw alignment system
US11896217B2 (en) 2020-10-29 2024-02-13 Cilag Gmbh International Surgical instrument comprising an articulation lock
US11534259B2 (en) 2020-10-29 2022-12-27 Cilag Gmbh International Surgical instrument comprising an articulation indicator
US11844518B2 (en) 2020-10-29 2023-12-19 Cilag Gmbh International Method for operating a surgical instrument
US11717289B2 (en) 2020-10-29 2023-08-08 Cilag Gmbh International Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable
US11617577B2 (en) 2020-10-29 2023-04-04 Cilag Gmbh International Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable
US11890010B2 (en) 2020-12-02 2024-02-06 Cllag GmbH International Dual-sided reinforced reload for surgical instruments
US11653915B2 (en) 2020-12-02 2023-05-23 Cilag Gmbh International Surgical instruments with sled location detection and adjustment features
US11653920B2 (en) 2020-12-02 2023-05-23 Cilag Gmbh International Powered surgical instruments with communication interfaces through sterile barrier
US11849943B2 (en) 2020-12-02 2023-12-26 Cilag Gmbh International Surgical instrument with cartridge release mechanisms
US11678882B2 (en) 2020-12-02 2023-06-20 Cilag Gmbh International Surgical instruments with interactive features to remedy incidental sled movements
US11744581B2 (en) 2020-12-02 2023-09-05 Cilag Gmbh International Powered surgical instruments with multi-phase tissue treatment
US11737751B2 (en) 2020-12-02 2023-08-29 Cilag Gmbh International Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings
US11627960B2 (en) 2020-12-02 2023-04-18 Cilag Gmbh International Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections
US11723657B2 (en) 2021-02-26 2023-08-15 Cilag Gmbh International Adjustable communication based on available bandwidth and power capacity
US11696757B2 (en) 2021-02-26 2023-07-11 Cilag Gmbh International Monitoring of internal systems to detect and track cartridge motion status
US11812964B2 (en) 2021-02-26 2023-11-14 Cilag Gmbh International Staple cartridge comprising a power management circuit
US11793514B2 (en) 2021-02-26 2023-10-24 Cilag Gmbh International Staple cartridge comprising sensor array which may be embedded in cartridge body
US11751869B2 (en) 2021-02-26 2023-09-12 Cilag Gmbh International Monitoring of multiple sensors over time to detect moving characteristics of tissue
US11749877B2 (en) 2021-02-26 2023-09-05 Cilag Gmbh International Stapling instrument comprising a signal antenna
US11701113B2 (en) 2021-02-26 2023-07-18 Cilag Gmbh International Stapling instrument comprising a separate power antenna and a data transfer antenna
US11925349B2 (en) 2021-02-26 2024-03-12 Cilag Gmbh International Adjustment to transfer parameters to improve available power
US11744583B2 (en) 2021-02-26 2023-09-05 Cilag Gmbh International Distal communication array to tune frequency of RF systems
US11730473B2 (en) 2021-02-26 2023-08-22 Cilag Gmbh International Monitoring of manufacturing life-cycle
US11717291B2 (en) 2021-03-22 2023-08-08 Cilag Gmbh International Staple cartridge comprising staples configured to apply different tissue compression
US11723658B2 (en) 2021-03-22 2023-08-15 Cilag Gmbh International Staple cartridge comprising a firing lockout
US11826012B2 (en) 2021-03-22 2023-11-28 Cilag Gmbh International Stapling instrument comprising a pulsed motor-driven firing rack
US11806011B2 (en) 2021-03-22 2023-11-07 Cilag Gmbh International Stapling instrument comprising tissue compression systems
US11737749B2 (en) 2021-03-22 2023-08-29 Cilag Gmbh International Surgical stapling instrument comprising a retraction system
US11826042B2 (en) 2021-03-22 2023-11-28 Cilag Gmbh International Surgical instrument comprising a firing drive including a selectable leverage mechanism
US11759202B2 (en) 2021-03-22 2023-09-19 Cilag Gmbh International Staple cartridge comprising an implantable layer
US11786239B2 (en) 2021-03-24 2023-10-17 Cilag Gmbh International Surgical instrument articulation joint arrangements comprising multiple moving linkage features
US11896219B2 (en) 2021-03-24 2024-02-13 Cilag Gmbh International Mating features between drivers and underside of a cartridge deck
US11903582B2 (en) 2021-03-24 2024-02-20 Cilag Gmbh International Leveraging surfaces for cartridge installation
US11849945B2 (en) 2021-03-24 2023-12-26 Cilag Gmbh International Rotary-driven surgical stapling assembly comprising eccentrically driven firing member
US11896218B2 (en) 2021-03-24 2024-02-13 Cilag Gmbh International Method of using a powered stapling device
US11786243B2 (en) 2021-03-24 2023-10-17 Cilag Gmbh International Firing members having flexible portions for adapting to a load during a surgical firing stroke
US11857183B2 (en) 2021-03-24 2024-01-02 Cilag Gmbh International Stapling assembly components having metal substrates and plastic bodies
US11793516B2 (en) 2021-03-24 2023-10-24 Cilag Gmbh International Surgical staple cartridge comprising longitudinal support beam
US11744603B2 (en) 2021-03-24 2023-09-05 Cilag Gmbh International Multi-axis pivot joints for surgical instruments and methods for manufacturing same
US11832816B2 (en) 2021-03-24 2023-12-05 Cilag Gmbh International Surgical stapling assembly comprising nonplanar staples and planar staples
US11849944B2 (en) 2021-03-24 2023-12-26 Cilag Gmbh International Drivers for fastener cartridge assemblies having rotary drive screws
US20220370691A1 (en) 2021-05-10 2022-11-24 Cilag Gmbh International Bioabsorbable staple comprising mechanism for delaying the absorption of the staple
US20220378424A1 (en) 2021-05-28 2022-12-01 Cilag Gmbh International Stapling instrument comprising a firing lockout

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0604022A1 (en) * 1992-12-22 1994-06-29 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method for its manufacture
US5419760A (en) 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
CA2178541C (en) * 1995-06-07 2009-11-24 Neal E. Fearnot Implantable medical device
US5843172A (en) * 1997-04-15 1998-12-01 Advanced Cardiovascular Systems, Inc. Porous medicated stent
DE19731021A1 (de) * 1997-07-18 1999-01-21 Meyer Joerg In vivo abbaubares metallisches Implantat
EP0966979B1 (de) 1998-06-25 2006-03-08 Biotronik AG Implantierbare, bioresorbierbare Gefässwandstütze, insbesondere Koronarstent
DE19945049A1 (de) * 1999-09-20 2001-03-22 Meyer Joerg Durch Korrosion abbaubare medizinische Implantate aus Wolframlegierungen
US20040106988A1 (en) * 2000-09-29 2004-06-03 Summers David P. Resorbable prosthesis for medical treatment
US7083642B2 (en) * 2000-12-22 2006-08-01 Avantec Vascular Corporation Delivery of therapeutic capable agents
DK1370306T3 (da) * 2001-01-05 2005-11-07 Jacqueline Yvonne Hausdorf Ved korrosion nedbrydelige metalliske medicinske implantater
NL1017672C2 (nl) * 2001-03-22 2002-09-24 Hendrik Glastra Implanteerbaar samenstel met therapeutische werking.
DE10128100A1 (de) 2001-06-11 2002-12-19 Hannover Med Hochschule Medizinisches Implantat für den menschlichen und tierischen Körper
US6939376B2 (en) * 2001-11-05 2005-09-06 Sun Biomedical, Ltd. Drug-delivery endovascular stent and method for treating restenosis
US20030093147A1 (en) * 2001-11-13 2003-05-15 Ogle Matthew F. Medical devices that stimulate growth factor production
DE10163106A1 (de) * 2001-12-24 2003-07-10 Univ Hannover Medizinische Implantate, Prothesen, Protheseteile, medizinische Instrumente, Geräte und Hilfsmittel aus einem halogenid-modifizierten Magnesiumwerkstoff
DE10237571A1 (de) * 2002-08-13 2004-02-26 Biotronik Meß- und Therapiegeräte GmbH & Co. Ingenieurbüro Berlin Endovaskuläres Implantat mit aktiver Beschichtung
DE10253634A1 (de) * 2002-11-13 2004-05-27 Biotronik Meß- und Therapiegeräte GmbH & Co. Ingenieurbüro Berlin Endoprothese
US20050027350A1 (en) * 2003-07-30 2005-02-03 Biotronik Mess-Und Therapiegeraete Gmbh & Co Ingenieurbuero Berlin Endovascular implant for the injection of an active substance into the media of a blood vessel

Also Published As

Publication number Publication date
CN1905913B (zh) 2010-10-06
JP2007520292A (ja) 2007-07-26
US20090182290A1 (en) 2009-07-16
US9095642B2 (en) 2015-08-04
JP4769730B2 (ja) 2011-09-07
DE102004029611A1 (de) 2005-08-25

Similar Documents

Publication Publication Date Title
CN1905913B (zh) 用于在身体介质流过的脉管中释放活性物质的植入物
US7238199B2 (en) Method and apparatus for stent deployment with enhanced delivery of bioactive agents
JP5918195B2 (ja) 生物浸食性マトリクスコア及び生物浸食性スキンを有する注射可能な持続的放出用の送達用デバイス
JP6767185B2 (ja) 微粒子が配置された弾性基質を有する挿入可能な医療機器、および薬物送達方法
EP0952867B1 (fr) Dispositif d'administration locale de formulations solides ou semi-solides
ES2321743T3 (es) Stents con revestimientos que liberan farmacos.
CN101854889B (zh) 用于药物输送的由具有螺旋形沟槽的导丝制成的支架
EP2251050A1 (en) Drug elution-type catheter and method for manufacturing the drug elution-type catheter
US20040013702A1 (en) Implantable devices for the controlled release of cytotoxic agents
JP2006500115A (ja) 密封小線源治療用の可撓性および/または弾性シードまたはストランド
JP2010540204A (ja) 内部薬物送達システムを備えた医療用インプラント
JP2006500996A (ja) 溶出性生体適合性移植可能医療器具を介してマイトマイシンを送達するための装置および方法
CN102056635A (zh) 可生物蚀解的内置假体
CN103143069A (zh) 用于整合入医疗装置的疏水性改善的药物
CN103108662A (zh) 用于装载药物溶出性医疗器械的设备和方法
CN200980748Y (zh) 一种药物洗脱器械的多孔药物释放结构
CN200980747Y (zh) 药物洗脱器械的药物释放结构
CA2552405C (en) Implant for releasing an active substance into a vessel through which a body medium flows
CN200970281Y (zh) 一种用于药物洗脱器械的储药及药物释放结构
CN101309706A (zh) 药剂释放控制组合物及药剂释放性医疗器具
DK2233112T3 (en) An injectable depot implant having a bioerodible matrix core and an outer membrane bioerodible
US9849005B2 (en) Implant and method for manufacturing same
CN201006051Y (zh) 局部多孔洞与少量聚合物共载的药物释放结构
KR20140057357A (ko) 생분해성 탄성 호일과 치료제로 피복된 클래드 방사선 불투과성 섬유로 이루어진 자체-팽창형 생분해성 스텐트 및 이들의 제조 방법
WO2023225101A1 (en) Core-shell microneedle patches and methods

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20180408

Address after: Swiss Army

Patentee after: Biotronik AG

Address before: Swiss Swiss

Patentee before: Biotronik Vi Patent AG

TR01 Transfer of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20101006

Termination date: 20200204

CF01 Termination of patent right due to non-payment of annual fee