公开(公告)号：US08703168B2

公开(公告)日：2014-04-22

申请号：US12109677

申请日：2008-04-25

Applicant: Aiden Flanagan ,  Robert Herrmann ,  Ken Merdan ,  Michael Kuehling ,  Barry O'Brien ,  Rajesh Radhakishnan ,  Torsten Scheuermann ,  Scott Schewe ,  Anurag Singhal ,  Young-Ho Song ,  Mary Joe Timm ,  Jan Weber ,  Yixin Xu

Inventor： Aiden Flanagan ,  Robert Herrmann ,  Ken Merdan ,  Michael Kuehling ,  Barry O'Brien ,  Rajesh Radhakishnan ,  Torsten Scheuermann ,  Scott Schewe ,  Anurag Singhal ,  Young-Ho Song ,  Mary Joe Timm ,  Jan Weber ,  Yixin Xu

IPC: A61F2/00

CPC classification number: A61F2/91 ,  A61F2/3094 ,  A61F2002/30677 ,  A61F2002/3068 ,  A61F2210/0076 ,  A61F2230/0013 ,  A61F2240/001 ,  A61F2250/0067 ,  A61F2250/0068

Abstract: An implantable medical device for releasing therapeutic agent having a medical device body and a plurality of reservoir-defining structures disposed on a surface of the body. A reservoir can be defined by the reservoir-defining structures and therapeutic agent may be located in the reservoir. A cover may extend over the reservoir so that the therapeutic agent is released from the reservoir when the medical device implanted. Methods for making the medical device may also include providing a medical device body, positioning a plurality of reservoir-defining structures on a surface of the body to form a reservoir, loading therapeutic agent into the reservoir, and covering the reservoir so that the therapeutic agent may release when the medical device is implanted. Alternatively, the reservoir may be covered with a cover and an opening formed in the cover so that the therapeutic agent may release when the medical device is implanted.

Abstract translation: 一种用于释放具有医疗装置主体的治疗剂的可植入医疗装置和设置在身体表面上的多个储存器限定结构。 储存器可以由储存器限定结构限定，并且治疗剂可以位于储存器中。 覆盖物可以延伸到储存器上方，使得当植入医疗装置时治疗剂从储存器释放。 用于制造医疗装置的方法还可以包括提供医疗装置主体，在身体的表面上定位多个储存器限定结构以形成储存器，将治疗剂装载到储存器中并覆盖储存器，使得治疗剂 当植入医疗器械时可能释放。 或者，储存器可覆盖有形成在盖中的盖和开口，使得治疗剂可以在植入医疗装置时释放。

公开(公告)号：US08574615B2

公开(公告)日：2013-11-05

申请号：US12787209

申请日：2010-05-25

Applicant: Barron Tenney ,  Yixin Xu ,  Michael N. Helmus

Inventor： Barron Tenney ,  Yixin Xu ,  Michael N. Helmus

IPC: A61F2/02

CPC classification number: A61F2/02 ,  A61F2/30767 ,  A61F2/82 ,  A61F2/91 ,  A61F2002/30677 ,  A61F2002/3068 ,  A61F2002/3084 ,  A61F2210/0076 ,  A61F2250/0068 ,  A61L29/146 ,  A61L29/16 ,  A61L31/146 ,  A61L31/16 ,  A61L2300/00 ,  A61L2400/12 ,  A61N1/375 ,  B82Y30/00

Abstract: According to an aspect of the present invention, implantable or insertable medical devices are provided which contain (a) one or more depressions that contain at least one therapeutic agent, and (b) a nanoporous coating, disposed over the therapeutic-agent-containing depressions, which regulate transport of species between the therapeutic-agent-containing depressions and the exterior of the device. The implantable or insertable devices are configured to preform a role beyond mere drug delivery, for example, providing mechanical and/or electrical functions within the body, among other functions. An advantage of the present invention is that medical devices may be provided, which release therapeutic agents in quantities far exceeding the void volume within the nanoporous coating, while at the same time providing functionality that extends beyond drug delivery. Such release may further approach or achieve a zero order kinetic drug release profile.

Abstract translation: 根据本发明的一个方面，提供了可植入或可插入的医疗装置，其包含（a）含有至少一种治疗剂的一种或多种凹陷，和（b）在含治疗剂的凹陷上设置的纳米多孔涂层 ，其调节物质在含治疗剂的凹陷和装置的外部之间的运输。 可植入或可插入的装置被配置为预防仅仅药物递送的作用，例如在体内提供机械和/或电功能等功能。 本发明的一个优点是可以提供医疗装置，其释放的量远远超过纳米多孔涂层内的空隙体积，同时提供延伸超出药物递送的功能。 这种释放可以进一步接近或实现零级动力学药物释放曲线。

公开(公告)号：US20100008970A1

公开(公告)日：2010-01-14

申请号：US12334113

申请日：2008-12-12

Applicant: Barry O'Brien ,  Ben Arcand ,  James Lee Shippy, III ,  Liliana Atanasoska ,  Aiden Flanagan ,  John T. Clarke ,  Tim O'Connor ,  Yixin Xu ,  Dave McMorrow ,  Jan Weber ,  John Kremer ,  Michael Kuehling ,  Dominique Seidel

Inventor： Barry O'Brien ,  Ben Arcand ,  James Lee Shippy, III ,  Liliana Atanasoska ,  Aiden Flanagan ,  John T. Clarke ,  Tim O'Connor ,  Yixin Xu ,  Dave McMorrow ,  Jan Weber ,  John Kremer ,  Michael Kuehling ,  Dominique Seidel

IPC: A61K31/337 ,  A61F2/00 ,  B05D1/02

CPC classification number: A61L31/088 ,  A61L31/16 ,  A61L2300/45 ,  A61L2300/61

Abstract: A drug-eluting endoprosthesis that includes a bioerodible metal portion and a therapeutic agent. In some aspects, the endoprosthesis includes a plurality of discrete deposits and a plurality of overlying layers each overlying one of the plurality of discrete deposits. Each discrete deposit includes one or more therapeutic agents and each overlying layer includes one or more bioerodible metals. In other aspects, the bioerodible metal portion includes at least two bioerodible metal regions having different electronegativities. The at least two bioerodible metal regions being in electrical contact with each other. The bioerodible metal erodes in a physiological environment to release the therapeutic agent.

Abstract translation: 包括生物腐蚀性金属部分和治疗剂的药物洗脱内用假体。 在一些方面，内假体包括多个离散沉积物和多个覆盖层，每个覆盖层覆盖多个离散沉积物之一。 每个离散沉积物包括一种或多种治疗剂，并且每个上覆层包括一种或多种生物可腐蚀金属。 在其他方面，生物腐蚀性金属部分包括具有不同电负性的至少两个生物可腐蚀金属区域。 所述至少两个生物浸渍金属区域彼此电接触。 生物腐蚀性金属在生理环境中侵蚀以释放治疗剂。

公开(公告)号：US20090118812A1

公开(公告)日：2009-05-07

申请号：US11934288

申请日：2007-11-02

Applicant: Jaydeep Y. Kokate ,  Raed Rizq ,  Jay Rassat ,  Derek Sutermeister ,  Samuel Robaina ,  Peter Edelman ,  Tom Holman ,  Michael Kuehling ,  Yixin Xu

Inventor： Jaydeep Y. Kokate ,  Raed Rizq ,  Jay Rassat ,  Derek Sutermeister ,  Samuel Robaina ,  Peter Edelman ,  Tom Holman ,  Michael Kuehling ,  Yixin Xu

IPC: A61F2/06

CPC classification number: A61L31/10 ,  A61L31/088 ,  A61L31/146 ,  A61L31/16 ,  A61L2300/00 ,  C23C14/06 ,  C23C14/3464

Abstract: A method includes: providing a substrate, depositing a ceramic and an extractable material onto the substrate, forming a porous structure in the ceramic by removing the extractable material, and utilizing the ceramic in an endoprosthesis. An endoprosthesis, such as a stent, including a coating formed of a ceramic and an extractable material that can be removed from the coating to form voids is also disclosed.

Abstract translation: 一种方法包括：提供衬底，将陶瓷和可提取材料沉积到衬底上，通过去除可提取材料在陶瓷中形成多孔结构，并在内置假体中利用陶瓷。 还公开了一种内置假体，例如支架，包括由陶瓷形成的涂层和可从涂层中除去以形成空隙的可提取材料。

公开(公告)号：US20090012603A1

公开(公告)日：2009-01-08

申请号：US12166377

申请日：2008-07-02

Applicant: Yixin Xu ,  Min-Shyan Sheu ,  Steve Walak

Inventor： Yixin Xu ,  Min-Shyan Sheu ,  Steve Walak

IPC: A61F2/82 ,  A61F2/00 ,  A61M37/00

CPC classification number: A61L31/16 ,  A61L31/14 ,  A61L31/146 ,  A61L2300/60 ,  A61L2300/608 ,  A61L2420/08

Abstract: The present invention is directed to implantable medical devices which may be used for controllably releasing a therapeutic agent within a patient and methods for making the same. These medical devices may include porous coatings, which may be polymer-free, located on an outer surface or abluminal surface of the medical device. The medical device may be a stent. The pores of the porous coating may be expandable to facilitate loading of the therapeutic agent. The medical device may be triggerable upon implantation of the medical device such that the volume of the voids shrinks to eject the therapeutic agent. The voids may be slots in the stent. Expandable materials or structures may be positioned in the voids to expand upon implantation and eject the therapeutic agent.

Abstract translation: 本发明涉及可用于可控地释放患者内的治疗剂的可植入医疗装置及其制造方法。 这些医疗装置可以包括位于医疗装置的外表面或外表面上的多孔涂层，其可以是无聚合物的。 医疗装置可以是支架。 多孔涂层的孔可以是可膨胀的，以便于治疗剂的加载。 医疗装置可以在植入医疗装置时触发，使得空隙的体积收缩以喷射治疗剂。 空隙可以是支架中的狭槽。 可膨胀材料或结构可以位于空隙中，以在植入时膨胀并喷射治疗剂。

公开(公告)号：US20080102194A1

公开(公告)日：2008-05-01

申请号：US11860866

申请日：2007-09-25

Applicant: Michael N. Helmus ,  Yixin Xu ,  John Benco

Inventor： Michael N. Helmus ,  Yixin Xu ,  John Benco

IPC: B05D1/18 ,  A61F2/06

CPC classification number: A61L31/10 ,  A61L31/146 ,  A61L31/16 ,  A61L2300/606 ,  A61L2420/02 ,  C23C18/1644 ,  C23C18/1662 ,  C23C18/44

Abstract: Methods and apparatus for coating surfaces of medical devices by electroless plating are disclosed. In one embodiment, the invention includes a coating method in which a therapeutic agent and a plating material are plated onto the surface of the medical device by an electroless plating chemical reaction. In another embodiment, a coating method is disclosed in which the coating is formed by suspending a therapeutic agent in a soluble plating solution and plating a plating material onto the medical device by electroless plating wherein the plated material contains the suspended therapeutic agent. In another embodiment, a coating method is provided wherein the coating is formed by initially bonding a therapeutic agent to a plating material, and then plating the bonded therapeutic agent/plating material onto the medical device by electroless plating. In another embodiment, an additive is introduced to the soluble plating solution to regulate the chemical reaction of electroless plating. In another embodiment, a coating method is provided wherein the surface of the medical device is treated, e.g. creating a porous surface layer, to increase the amount of the therapeutic agent that may be plated onto the medical device by electroless plating. The coating is formed by plating a therapeutic agent into and/or onto the porous surface layer. These methods and apparatus are used to apply one or more coating materials, simultaneously or in sequence. In certain embodiments of the invention, the coating materials include therapeutic agents and cationic drugs.

Abstract translation: 公开了通过化学镀涂覆医疗器械表面的方法和装置。 在一个实施方案中，本发明包括通过化学镀化学反应将治疗剂和电镀材料镀在医疗装置的表面上的涂布方法。 在另一个实施方案中，公开了一种涂覆方法，其中通过将治疗剂悬浮在可溶性电镀溶液中并通过化学镀将电镀材料镀覆到医疗装置上而形成涂层，其中电镀材料含有悬浮治疗剂。 在另一个实施方案中，提供了涂覆方法，其中通过首先将治疗剂粘合到电镀材料上形成所述涂层，然后通过无电镀将所述结合的治疗剂/电镀材料电镀到所述医疗装置上。 在另一个实施方案中，将添加剂引入到可溶性电镀溶液中以调节化学镀的化学反应。 在另一个实施例中，提供一种涂覆方法，其中治疗医疗装置的表面，例如， 产生多孔表面层，以通过无电镀来增加可镀在医疗装置上的治疗剂的量。 通过将治疗剂镀在多孔表面层中和/或之上而形成涂层。 这些方法和装置用于同时或按顺序施加一种或多种涂层材料。 在本发明的某些实施方案中，涂层材料包括治疗剂和阳离子药物。

公开(公告)号：US20070224235A1

公开(公告)日：2007-09-27

申请号：US11388604

申请日：2006-03-24

Applicant: Barron Tenney ,  Yixin Xu ,  Michael Helmus

Inventor： Barron Tenney ,  Yixin Xu ,  Michael Helmus

IPC: A61F2/06

CPC classification number: A61F2/02 ,  A61F2/30767 ,  A61F2/82 ,  A61F2/91 ,  A61F2002/30677 ,  A61F2002/3068 ,  A61F2002/3084 ,  A61F2210/0076 ,  A61F2250/0068 ,  A61L29/146 ,  A61L29/16 ,  A61L31/146 ,  A61L31/16 ,  A61L2300/00 ,  A61L2400/12 ,  A61N1/375 ,  B82Y30/00

Abstract: According to an aspect of the present invention, implantable or insertable medical devices are provided which contain (a) one or more depressions that contain at least one therapeutic agent, and (b) a nanoporous coating, disposed over the therapeutic-agent-containing depressions, which regulate transport of species between the therapeutic-agent-containing depressions and the exterior of the device. The implantable or insertable devices are configured to preform a role beyond mere drug delivery, for example, providing mechanical and/or electrical functions within the body, among other functions. An advantage of the present invention is that medical devices may be provided, which release therapeutic agents in quantities far exceeding the void volume within the nanoporous coating, while at the same time providing functionality that extends beyond drug delivery. Such release may further approach or achieve a zero order kinetic drug release profile.

Abstract translation: 根据本发明的一个方面，提供了可植入或可插入的医疗装置，其包含（a）含有至少一种治疗剂的一种或多种凹陷，和（b）在含治疗剂的凹陷上设置的纳米多孔涂层 ，其调节物质在含治疗剂的凹陷和装置的外部之间的运输。 可植入或可插入的装置被配置为预防仅仅药物递送的作用，例如在体内提供机械和/或电功能等功能。 本发明的一个优点是可以提供医疗装置，其释放的量远远超过纳米多孔涂层内的空隙体积，同时提供延伸超出药物递送的功能。 这种释放可以进一步接近或实现零级动力学药物释放曲线。

公开(公告)号：US20060129215A1

公开(公告)日：2006-06-15

申请号：US11007867

申请日：2004-12-09

Applicant: Michael Helmus ,  Yixin Xu ,  Shrirang Ranade

Inventor： Michael Helmus ,  Yixin Xu ,  Shrirang Ranade

IPC: A61N1/05

CPC classification number: B82Y30/00 ,  A61L27/50 ,  A61L27/54 ,  A61L27/56 ,  A61L2300/236 ,  A61L2300/252 ,  A61L2300/416 ,  A61L2300/42 ,  A61L2300/45 ,  A61L2300/624 ,  A61N1/05 ,  B82Y5/00

Abstract: According to certain aspects of the invention, implantable or insertable medical devices are provided that contain one or more nanoporous regions, which may further comprise interconnected nanopores. Other aspects of the invention are directed to implantable or insertable medical devices that contain one or more nanostructured regions, which are formed by a variety of methods. Still other aspects of the invention are directed to implantable or insertable medical devices having nanotextured surface regions, in which cell-adhesion-promoting biomolecules (e.g., glycosaminoglycans, proteoglycans, cell adhesion peptides, and adhesive proteins) are provided on, within or beneath the nanotextured surface regions.

Abstract translation: 根据本发明的某些方面，提供了可植入或可插入的医疗装置，其包含一个或多个纳米多孔区域，其可以进一步包括互连的纳米孔。 本发明的其它方面涉及含有一个或多个纳米结构区域的可植入或可插入的医疗装置，其通过多种方法形成。 本发明的另外其它方面涉及具有纳米纹理表面区域的可植入或可插入的医疗装置，其中提供细胞粘附促进生物分子（例如，糖胺聚糖，蛋白聚糖，细胞粘附肽和粘合蛋白），其中， 纳米纹理表面区域。

公开(公告)号：US20060124466A1

公开(公告)日：2006-06-15

申请号：US11007297

申请日：2004-12-09

Applicant: Yixin Xu ,  Michael Helmus

Inventor： Yixin Xu ,  Michael Helmus

IPC: C25D15/00

CPC classification number: A61L31/10 ,  A61L31/082 ,  A61L31/16 ,  A61L2300/606 ,  A61L2420/02 ,  C09D5/4492 ,  C25D9/00 ,  C25D9/02 ,  C25D15/00

Abstract: Methods and apparatuses for coating surfaces of medical devices by electroplating are disclosed. In one embodiment, the invention includes a coating method in which a mixture of a therapeutic agent, and a plating material are electroplated onto the surface of the medical device. The electroplating method may be performed at a relatively low temperature to avoid destruction of the therapeutic agent. In another embodiment, a coating method is disclosed in which the coating is formed by suspending a therapeutic agent in an electrolytic solution and electroplating a plating material onto the medical device wherein the plating material carries the suspended therapeutic agent. Thus, the coating of plating material contains the suspended therapeutic agent. These methods and apparatuses are used to apply one or more coating materials, simultaneously or in sequence by varying the electroplating voltage. In certain embodiments of the invention, the coating materials include therapeutic agents and cationic drugs.

Abstract translation: 公开了通过电镀来涂覆医疗装置的表面的方法和装置。 在一个实施方案中，本发明包括将治疗剂和电镀材料的混合物电镀在医疗装置的表面上的涂布方法。 电镀方法可以在相对低的温度下进行以避免治疗剂的破坏。 在另一个实施方案中，公开了一种涂覆方法，其中通过将治疗剂悬浮在电解液中并将电镀材料电镀到医疗装置上而形成涂层，其中电镀材料携带悬浮的治疗剂。 因此，电镀材料的涂层含有悬浮治疗剂。 这些方法和装置用于通过改变电镀电压同时或依次施加一种或多种涂层材料。 在本发明的某些实施方案中，涂层材料包括治疗剂和阳离子药物。

公开(公告)号：US08388678B2

公开(公告)日：2013-03-05

申请号：US12333909

申请日：2008-12-12

Applicant: Anurag Singhal ,  Robert A. Herrmann ,  Yixin Xu ,  Young-Ho Song

Inventor： Anurag Singhal ,  Robert A. Herrmann ,  Yixin Xu ,  Young-Ho Song

IPC: A61F2/06

CPC classification number: A61L31/14 ,  A61L27/50 ,  A61L27/54 ,  A61L27/56 ,  A61L29/14 ,  A61L29/146 ,  A61L29/16 ,  A61L31/146 ,  A61L31/16 ,  A61L2300/602

Abstract: According to an aspect of the present invention, implantable or insertable medical devices are provided which contain the following: (a) substrate having one or more depressions that contain at least one therapeutic agent and (b) a porous membrane disposed over the substrate and the one or more depressions, which regulate transport of chemical species between the therapeutic-agent-containing depressions and the exterior of the device. The substrate and the porous membrane are formed of different materials each with a different thermal expansion coefficient. Moreover, one of the substrate and the porous membrane at least partially surrounds the other. Other aspects of the present invention are directed to methods of making such medical devices, and methods of treatment using such medical devices.

Abstract translation: 根据本发明的一个方面，提供了可植入或可插入的医疗装置，其包含以下内容：（a）具有一个或多个凹陷的基底，其含有至少一种治疗剂，和（b）设置在基底上的多孔膜， 一个或多个凹陷，其调节化学物质在含治疗剂的凹陷和装置的外部之间的运输。 基板和多孔膜由各自具有不同热膨胀系数的不同材料形成。 此外，衬底和多孔膜中的一个至少部分地围绕另一个。 本发明的其它方面涉及制造这种医疗装置的方法，以及使用这种医疗装置的治疗方法。