公开(公告)号：US08927049B2

公开(公告)日：2015-01-06

申请号：US12854463

申请日：2010-08-11

Applicant: Vipul Dave ,  Robert Falotico ,  Chengxue Li ,  Thai M. Nguyen ,  Theodore L. Parker ,  Jonathon Z. Zhao

Inventor： Vipul Dave ,  Robert Falotico ,  Chengxue Li ,  Thai M. Nguyen ,  Theodore L. Parker ,  Jonathon Z. Zhao

IPC: A61F2/06 ,  A61L33/00 ,  B05D3/00 ,  B05D1/32 ,  A61L31/16 ,  A61F2/91 ,  A61L31/10

CPC classification number: A61F2/91 ,  A61F2250/0068 ,  A61L31/10 ,  A61L31/16 ,  A61L33/0011 ,  A61L2300/00

Abstract: An expandable medical device includes a plurality of elongated struts, forming a substantially cylindrical device which is expandable from a first diameter to a second diameter. A plurality of different beneficial agents may be loaded into different openings within the struts for delivery to the tissue. For treatment of conditions such as restenosis, different agents are loaded into different openings in the device to address different biological processes involved in restenosis and are delivered at different release kinetics matched to the biological process treated. The different agents may also be used to address different diseases from the same drug delivery device. In addition, anti-thrombotic agents may be affixed to at least a portion of the surfaces of the medical device for the prevention of sub-acute thrombosis. To ensure that the different agents remain affixed to the device as well as to each other, masking and de-masking processes may be utilized.

Abstract translation: 可扩张医疗装置包括多个细长的支柱，形成从第一直径扩展到第二直径的基本上圆柱形的装置。 多个不同的有益剂可以被装载到支柱内的不同开口中，以便输送到组织。 为了治疗诸如再狭窄的病症，将不同的药剂装入装置中的不同开口以解决与再狭窄相关的不同生物过程，并且以与所治疗的生物过程相匹配的不同释放动力学递送。 不同的药剂也可用于解决来自同一药物递送装置的不同疾病。 此外，抗血栓形成剂可以附着在医疗装置的至少一部分表面上，以防止亚急性血栓形成。 为了确保不同的代理保持固定到设备以及彼此之间，可以利用掩蔽和去掩蔽处理。

公开(公告)号：US08911764B2

公开(公告)日：2014-12-16

申请号：US13075553

申请日：2011-03-30

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61F2/02 ,  A61L31/10 ,  C08J7/04 ,  C09D167/04 ,  C09D4/00

CPC classification number: A61L31/16 ,  A61K9/0024 ,  A61L27/54 ,  A61L31/10 ,  A61L31/12 ,  A61L2300/41 ,  A61L2300/416 ,  A61L2300/42 ,  A61L2420/02 ,  A61L2420/06 ,  A61L2420/08 ,  C08J7/047 ,  C08J2467/00 ,  C08J2483/00 ,  C09D4/00 ,  C09D167/04 ,  Y10T29/49984 ,  Y10T428/31511 ,  Y10T428/31525 ,  Y10T428/31529 ,  Y10T428/31663 ,  C08L67/04 ,  C08L83/04 ,  C08G77/28

Abstract: Coatings are provided in which surfaces may be activated by covalently bonding a combination of silane derivatives (A) to the metal surface, covalently bonding a lactone polymer (B) to the silane derivative by in situ ring opening polymerization, and depositing at least one layer of a polyester (C) on the bonded lactone polymer. Biologically active agents or therapeutic compounds may be deposited with any of the polyester layers. Such coated surfaces may be useful in medical devices, in particular stents.

Abstract translation: 提供了涂层，其中可以通过将硅烷衍生物（A）的组合与金属表面共价键合来活化，通过原位开环聚合将内酯聚合物（B）共价键合到硅烷衍生物上，并沉积至少一层 的聚酯（C）在粘合的内酯聚合物上。 生物活性剂或治疗化合物可以沉积任何聚酯层。 这种涂覆的表面可用于医疗装置，特别是支架。

公开(公告)号：US08557272B2

公开(公告)日：2013-10-15

申请号：US13086514

申请日：2011-04-14

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61F2/00 ,  A61L31/16

CPC classification number: A61L31/16 ,  A61K31/337 ,  A61K31/4355 ,  A61K31/436 ,  A61K31/4745 ,  A61L29/16 ,  A61L2300/416 ,  A61L2300/428 ,  A61L2300/802

Abstract: Medical devices may be utilized for local and regional therapeutic agent delivery. These therapeutic agents or compounds may reduce a biological organism's reaction to the introduction of the medical device to the organism. In addition, these therapeutic drugs, agents and/or compounds may be utilized to promote healing, including the prevention of thrombosis. The drugs, agents, and/or compounds may also be utilized to treat specific disorders, including restenosis, vulnerable plaque, and atherosclerosis in type 2 diabetic patients. In regional delivery, liquid formulations may be desirable to increase the efficacy and deliverability of the particular drug. Various materials and coating methodologies may be utilized to maintain the agents or compounds on the medical device until delivered and positioned.

Abstract translation: 医疗器械可用于局部和区域治疗剂递送。 这些治疗剂或化合物可以减少生物体对将生物体引入医疗装置的反应。 此外，这些治疗药物，药剂和/或化合物可用于促进愈合，包括预防血栓形成。 药物，药剂和/或化合物也可用于治疗2型糖尿病患者中的特定疾病，包括再狭窄，易损斑块和动脉粥样硬化。 在区域递送中，液体制剂可能是期望的，以增加特定药物的功效和递送能力。 可以使用各种材料和涂覆方法来将药剂或化合物维持在医疗装置上，直到被输送和定位。

公开(公告)号：US20130172986A1

公开(公告)日：2013-07-04

申请号：US13751997

申请日：2013-01-28

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61F2/00 ,  C09D133/14

CPC classification number: A61F2/0077 ,  A61F2/91 ,  A61F2250/0068 ,  A61L31/10 ,  A61L31/16 ,  A61L33/08 ,  A61L2300/42 ,  C09D133/14 ,  C08L67/04 ,  C08L29/04 ,  C08L5/10

Abstract: An implantable device having a coating comprising a comb-type anti-thrombotic conjugate to prevent or reduce the formation of thrombosis on the surface of the device. The device includes a frame expandable from a first diameter to a second diameter wherein the frame has an inner surface and an outer surface, a plurality of structural features disposed along the frame and a plurality of polymer anti-thrombotic conjugate particles situated with the plurality of structural features. The particle can be created utilizing the comb type polymer and heparin conjugate as a carrier for a therapeutic agent within its polymer matrix. The structural features allow for particles having differing properties to be placed at various locations along the device. Moreover, particles having at least two different agents can be located within the same structural feature.

Abstract translation: 一种可植入装置，其具有包含梳状抗血栓形成共轭物的涂层，以防止或减少装置表面上的血栓形成。 该装置包括可从第一直径扩展到第二直径的框架，其中框架具有内表面和外表面，沿着框架设置的多个结构特征以及多个聚合物抗血栓形成共轭物颗粒， 结构特征。 可以使用梳型聚合物和肝素缀合物作为其聚合物基质内的治疗剂的载体来产生颗粒。 结构特征允许具有不同性质的颗粒放置在沿设备的各个位置。 此外，具有至少两种不同试剂的颗粒可以位于相同的结构特征内。

公开(公告)号：US08383156B2

公开(公告)日：2013-02-26

申请号：US11741997

申请日：2007-04-30

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61K9/14 ,  A61K31/74

CPC classification number: A61F2/0077 ,  A61F2/91 ,  A61F2250/0068 ,  A61L31/10 ,  A61L31/16 ,  A61L33/08 ,  A61L2300/42 ,  C09D133/14 ,  C08L67/04 ,  C08L29/04 ,  C08L5/10

Abstract: Methods for making comb-type antithrombotic conjugate wherein substantially all side chains of water soluble poly(vinyl alcohol) (PVA) are extended by ring-opening polymerization to form a copolymer wherein substantially all terminals are conjugated to an antithrombotic molecule. In addition, a method is provided for applying a coating comprising a comb-type anti-thrombotic conjugate to at least a portion of an implantable device to prevent or reduce the formation of thrombosis on the surface of the device. A first or sub-layer of the coating is prepared by mixing a polymeric material and a biologically active agent with a solvent, thereby forming a homogeneous solution. A second or outer layer comprising a comb-type anti-thrombotic conjugate may be applied over the inner drug-containing layers using, for example, a dip coating or spray coating process. Alternatively the comb-type antithrombotic conjugate may be used as a matrix material to encapsulate a pharmaceutical agent to form microspheres or nanospheres before depositing the microspheres or nanospheres onto a medical device.

Abstract translation: 制备梳状抗血栓缀合物的方法，其中水溶性聚（乙烯醇）（PVA）的基本上所有侧链通过开环聚合延伸以形成基本上所有末端与抗血栓形成分子缀合的共聚物。 此外，提供了一种用于将包含梳型抗血栓形成结合物的涂层施用于可植入装置的至少一部分以防止或减少装置表面上形成血栓形成的方法。 通过将聚合材料和生物活性剂与溶剂混合制备涂层的第一层或次层，由此形成均匀溶液。 可以使用例如浸涂或喷涂方法将包含梳型抗血栓形成缀合物的第二层或外层涂覆在内含药物层上。 或者，梳状抗血栓缀合物可以用作基质材料，以在将微球或纳米球沉积到医疗装置上之前封装药剂以形成微球或纳米球。

公开(公告)号：US20120276172A1

公开(公告)日：2012-11-01

申请号：US13544043

申请日：2012-07-09

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61K9/00 ,  A61P7/02 ,  A61P29/00

CPC classification number: A61L31/10 ,  A61L27/16 ,  A61L27/34 ,  A61L27/54 ,  A61L29/041 ,  A61L29/085 ,  A61L29/16 ,  A61L31/048 ,  A61L31/16 ,  A61L2300/216 ,  A61L2300/41 ,  A61L2300/416 ,  A61L2300/42 ,  A61L2300/606 ,  A61L2420/06 ,  C08L27/12

Abstract: The present invention includes biocompatible polymeric coatings, membranes, matrices, and films to be used with implantable medical devices. Medical devices containing such materials applied to a surface thereof contain a film-forming fluorous homo-polymer or copolymer containing the polymerized residue of a fluorous moiety, wherein the relative amounts of the polymerized residues of one or more moieties are effective to provide the coating and films with properties effective for use in coating implantable med devices.

Abstract translation: 本发明包括与可植入医疗装置一起使用的生物相容性聚合物涂层，膜，基质和膜。 包含施用于其表面的这种材料的医疗装置包含含有氟部分的聚合残基的成膜氟聚合物或共聚物，其中一个或多个部分的聚合残基的相对量有效提供涂层和 具有有效用于涂覆可植入医疗器械的性质的膜。

公开(公告)号：US08216600B2

公开(公告)日：2012-07-10

申请号：US11939805

申请日：2007-11-14

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61L33/00 ,  A61F2/82

CPC classification number: A61L31/10 ,  A61L27/16 ,  A61L27/34 ,  A61L27/54 ,  A61L29/041 ,  A61L29/085 ,  A61L29/16 ,  A61L31/048 ,  A61L31/16 ,  A61L2300/216 ,  A61L2300/41 ,  A61L2300/416 ,  A61L2300/42 ,  A61L2300/606 ,  A61L2420/06 ,  C08L27/12

Abstract: The present invention includes biocompatible polymeric coatings, membranes, matrices, and films to be used with implantable medical devices. Medical devices containing such materials applied to a surface thereof contain a film-forming fluorous homo-polymer or copolymer containing the polymerized residue of a fluorous moiety, wherein the relative amounts of the polymerized residues of one or more moieties are effective to provide the coating and films with properties effective for use in coating implantable med devices.

Abstract translation: 本发明包括与可植入医疗装置一起使用的生物相容性聚合物涂层，膜，基质和膜。 包含施用于其表面的这种材料的医疗装置包含含有氟部分的聚合残基的成膜氟聚合物或共聚物，其中一个或多个部分的聚合残基的相对量有效提供涂层和 具有有效用于涂覆可植入医疗器械的性质的膜。

公开(公告)号：US20110245332A1

公开(公告)日：2011-10-06

申请号：US13158610

申请日：2011-06-13

Applicant: Robert Falotico ,  Jonathon Z. Zhao

Inventor： Robert Falotico ,  Jonathon Z. Zhao

IPC: A61K31/337 ,  A61P9/00

CPC classification number: A61K9/0019 ,  A61K9/19 ,  A61K31/337 ,  A61K47/22

Abstract: Medical devices, and in particular implantable medical devices, may be coated to minimize or substantially eliminate a biological organism's reaction to the introduction of the medical device to the organism. The medical devices may be coated with any number of biocompatible materials. Therapeutic drugs, agents or compounds may be mixed with the biocompatible materials and affixed to at least a portion of the medical device. These therapeutic drugs, agents or compounds may also further reduce a biological organism's reaction to the introduction of the medical device to the organism. In addition, these therapeutic drugs, agents and/or compounds may be utilized to promote healing, including the formation of blood clots. The drugs, agents, and/or compounds may also be utilized to treat specific diseases, including vulnerable plaque. Therapeutic agents may also be delivered to the region of a disease site. In regional delivery, liquid formulations may be desirable to increase the efficacy and deliverability of the particular drug. Also, the devices may be modified to promote endothelialization. Various materials and coating methodologies may be utilized to maintain the drugs, agents or compounds on the medical device until delivered and positioned. In addition, the devices utilized to deliver the implantable medical devices may be modified to reduce the potential for damaging the implantable medical device during deployment. Medical devices include stents, grafts, anastomotic devices, perivascular wraps, sutures and staples. In addition, various polymer combinations may be utilized to control the elution rates of the therapeutic drugs, agents and/or compounds from the implantable medical devices. Liquid formulations, including solutions and suspensions of the various drugs, agents and/or compounds, may be locally or regionally delivered. In each of these instances, antioxidants are utilized to prolong product integrity.

公开(公告)号：US20110190876A1

公开(公告)日：2011-08-04

申请号：US13086514

申请日：2011-04-14

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61F2/82 ,  A61F2/00 ,  A61K31/337 ,  A61P9/00 ,  B05D1/00 ,  B05D3/00

CPC classification number: A61L31/16 ,  A61K31/337 ,  A61K31/4355 ,  A61K31/436 ,  A61K31/4745 ,  A61L29/16 ,  A61L2300/416 ,  A61L2300/428 ,  A61L2300/802

Abstract: Medical devices may be utilized for local and regional therapeutic agent delivery. These therapeutic agents or compounds may reduce a biological organism's reaction to the introduction of the medical device to the organism. In addition, these therapeutic drugs, agents and/or compounds may be utilized to promote healing, including the prevention of thrombosis. The drugs, agents, and/or compounds may also be utilized to treat specific disorders, including restenosis, vulnerable plaque, and atherosclerosis in type 2 diabetic patients. In regional delivery, liquid formulations may be desirable to increase the efficacy and deliverability of the particular drug. Various materials and coating methodologies may be utilized to maintain the agents or compounds on the medical device until delivered and positioned.

Abstract translation: 医疗器械可用于局部和区域治疗剂递送。 这些治疗剂或化合物可以减少生物体对将生物体引入医疗装置的反应。 此外，这些治疗药物，药剂和/或化合物可用于促进愈合，包括预防血栓形成。 药物，药剂和/或化合物也可用于治疗2型糖尿病患者中的特定疾病，包括再狭窄，易损斑块和动脉粥样硬化。 在区域递送中，液体制剂可能是期望的，以增加特定药物的功效和递送能力。 可以使用各种材料和涂覆方法来将药剂或化合物维持在医疗装置上，直到被输送和定位。

公开(公告)号：US20110178595A1

公开(公告)日：2011-07-21

申请号：US13075553

申请日：2011-03-30

Applicant: Jonathon Z. Zhao

Inventor： Jonathon Z. Zhao

IPC: A61F2/82 ,  C08G77/392 ,  B32B9/04 ,  B05D3/10

CPC classification number: A61L31/16 ,  A61K9/0024 ,  A61L27/54 ,  A61L31/10 ,  A61L31/12 ,  A61L2300/41 ,  A61L2300/416 ,  A61L2300/42 ,  A61L2420/02 ,  A61L2420/06 ,  A61L2420/08 ,  C08J7/047 ,  C08J2467/00 ,  C08J2483/00 ,  C09D4/00 ,  C09D167/04 ,  Y10T29/49984 ,  Y10T428/31511 ,  Y10T428/31525 ,  Y10T428/31529 ,  Y10T428/31663 ,  C08L67/04 ,  C08L83/04 ,  C08G77/28

Abstract: Coatings are provided in which surfaces may be activated by covalently bonding a combination of silane derivatives (A) to the metal surface, covalently bonding a lactone polymer (B) to the silane derivative by in situ ring opening polymerization, and depositing at least one layer of a polyester (C) on the bonded lactone polymer. Biologically active agents or therapeutic compounds may be deposited with any of the polyester layers. Such coated surfaces may be useful in medical devices, in particular stents.

Abstract translation: 提供了涂层，其中可以通过将硅烷衍生物（A）的组合与金属表面共价键合来活化，通过原位开环聚合将内酯聚合物（B）共价键合到硅烷衍生物上，并沉积至少一层 的聚酯（C）在粘合的内酯聚合物上。 生物活性剂或治疗化合物可以沉积任何聚酯层。 这种涂覆的表面可用于医疗装置，特别是支架。