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    Calcification-resistant materials and methods of making same through use of multivalent cations
    1.
    发明授权
    Calcification-resistant materials and methods of making same through use of multivalent cations 失效
    通过使用多价阳离子，耐钙材料及其制备方法

    公开(公告)号：US5679112A

    公开(公告)日：1997-10-21

    申请号：US345658

    申请日：1994-11-28

    申请人： Robert J. Levy ,  Amnon Sintov

    发明人： Robert J. Levy ,  Amnon Sintov

    IPC分类号： A61L27/36 ,  A61L27/50 ,  A61L27/54 ,  C14C3/00 ,  A61F2/02

    CPC分类号： A61L27/50 ,  A61L27/3604 ,  A61L27/3687 ,  A61L27/54 ,  A61L2300/102 ,  A61L2300/21 ,  A61L2300/216 ,  A61L2300/40 ,  A61L2300/45 ,  A61L2400/02 ,  A61L2430/40 ,  Y10S128/08 ,  Y10S623/921

    摘要： Bioprosthetic materials, either natural or synthetic, are treated with trivalent iron cations, or salts, to prevent in vivo calcification. Such bioprosthetic materials include porcine aortic valve leaflets, bovine pericardium, aortic homografts, biocompatible elastomers, and the like which are intended for invasive, or in-dwelling use in a human or animal body. Simple incubation of the natural bioprosthetic materials in an iron ion-containing solution, such as aqueous FeCl.sub.3, particularly with the addition of an anticalcification agent, such as a diphosphonate, prior to implantation has been found to inhibit calcification of the biomaterial over a prolonged period, and to do so without adverse side effects. Incorporation of an iron-containing compound, with or without an additional anticalcification agent, into the formulation for polymers, such as polyurethane, has also been found to inhibit calcification with no adverse side effects.

    摘要翻译： 天然或合成的生物假体材料用三价铁阳离子或盐处理，以防止体内钙化。 这样的生物假体材料包括旨在用于人或动物体内的侵入性或住宅用的猪主动脉瓣瓣叶，牛心包膜，主动脉同种异体移植物，生物相容性弹性体等。 天然生物假体材料在含铁离子的溶液（如FeCl 3水溶液）中特别是在植入前特别是加入抗细胞剂如二膦酸盐的简单温育已被发现能够在长时间内抑制生物材料钙化 ，并且没有不利的副作用。 含有或不含额外抗氧化剂的含铁化合物掺入用于聚合物如聚氨酯的聚合物的制剂中也被发现抑制钙化而没有不利的副作用。

    System for controlled release of antiarrhythmic agents
    2.
    发明授权
    System for controlled release of antiarrhythmic agents 失效
    用于控制释放抗心律失常药物的系统

    公开(公告)号：US5387419A

    公开(公告)日：1995-02-07

    申请号：US37810

    申请日：1993-03-26

    申请人： Robert J. Levy ,  Amnon Sintov

    发明人： Robert J. Levy ,  Amnon Sintov

    IPC分类号： A61K9/00 ,  A61K9/70

    CPC分类号： A61K9/0024 ,  A61K9/7007 ,  Y10S514/821

    摘要： A system for controlled release, site-specific delivery of therapeutic agents, particularly myocardial agents such as antiarrhythmic agents, comprises a biocompatible polymeric matrix with an incorporated therapeutic agent for direct placement at the epicardium. Advantageously, the dosage form can be fabricated in such a manner as to tailor the release characteristics as required by the nature of the physical condition desired to be treated. In a specific illustrative embodiment, lidocaine, an antiarrhythmic depressant, is incorporated in polyurethane by a unique method which permits drug-loading of the polymeric matrix from about 5% up to 40% by weight, with about 25% to 30% in a preferred embodiment. A novel FeCl.sub.3 catalyst causes the polyurethane to polymerize despite the presence of drug in the polymeric matrix mixture.

    摘要翻译： 用于受控释放，特定地点递送治疗剂，特别是心肌药物如抗心律失常剂的系统包括具有用于直接置于心外膜的并入治疗剂的生物相容性聚合物基质。 有利地，剂型可以按照所需待处理的物理条件的性质来定制释放特性的方式制造。 在具体的说明性实施方案中，通过独特的方法将利多卡因，抗心律失常抑制剂掺入聚氨酯中，其允许聚合物基质的药物加载量为约5％至40％重量，优选的为约25％至30％ 实施例。 尽管在聚合物基质混合物中存在药物，但新型FeCl 3催化剂使聚氨酯聚合。

    Calcification-resistant materials and methods of making same through use of multivalent cations
    3.
    发明授权
    Calcification-resistant materials and methods of making same through use of multivalent cations 失效
    通过使用多价阳离子，耐钙材料及其制备方法

    公开(公告)号：US5368608A

    公开(公告)日：1994-11-29

    申请号：US689652

    申请日：1991-04-23

    申请人： Robert J. Levy ,  Amnon Sintov

    发明人： Robert J. Levy ,  Amnon Sintov

    IPC分类号： A61L27/36 ,  A61L27/50 ,  A61L27/54 ,  A61L17/00 ,  A61F2/06 ,  C14C3/00

    CPC分类号： A61L27/50 ,  A61L27/3604 ,  A61L27/3687 ,  A61L27/54 ,  A61L2300/102 ,  A61L2300/21 ,  A61L2300/216 ,  A61L2300/40 ,  A61L2300/45 ,  A61L2400/02 ,  A61L2430/40 ,  Y10S128/08 ,  Y10S623/921

    摘要： Bioprosthetic materials, either natural or synthetic, are treated with trivalent aluminum or iron cations, or salts, to prevent in vivo calcification. Such bioprosthetic materials include porcine aortic valve leaflets, bovine pericardium, aortic homografts, biocompatible elastomers, and the like which are intended for invasive, or in-dwelling use in a human or animal body. Simple incubation of the natural bioprosthetic materials in an ion-containing solution, such as aqueous AlCl.sub.3 or FeCl.sub.3, prior to implantation has been found to inhibit calcification of the biomaterial over a prolonged period, and to do so without adverse side effects. Incorporation of an aluminum-containing compound into the formulation for polymers, such as polyurethane, has also been found to inhibit calcification with no adverse side effects.

    摘要翻译： 天然或合成的生物假体材料用三价铝或铁阳离子或盐处理，以防止体内钙化。 这样的生物假体材料包括旨在用于人或动物体内的侵入性或住宅用的猪主动脉瓣瓣叶，牛心包膜，主动脉同种异体移植物，生物相容性弹性体等。 已经发现在植入之前将天然生物假体材料简单温育在含离子的溶液中，例如AlCl 3或FeCl 3水溶液，以在长时间内抑制生物材料的钙化，并且在没有不利副作用的情况下进行。 也已经发现将含铝化合物掺入聚合物如聚氨酯的制剂中可抑制钙化而没有不利的副作用。

    Calcification-resistant materials and methods of making same through use of trivalent aluminum
    4.
    发明授权
    Calcification-resistant materials and methods of making same through use of trivalent aluminum 失效
    通过使用三价铝，耐钙材料及其制备方法

    公开(公告)号：US5094661A

    公开(公告)日：1992-03-10

    申请号：US176789

    申请日：1988-04-01

    申请人： Robert J. Levy ,  Amnon Sintov

    发明人： Robert J. Levy ,  Amnon Sintov

    IPC分类号： A61L27/36 ,  A61L27/50 ,  A61L27/54

    CPC分类号： A61L27/3687 ,  A61L27/50 ,  A61L27/54 ,  A61L2300/102 ,  A61L2400/02 ,  A61L2430/40 ,  Y10S623/92

    摘要： Bioprosthetic materials, either natural or synthetic, are treated with trivalent aluminum cations to prevent in vivo calcification. Such bioprosthetic materials include porcine aortic valve leaflets, bovine pericardium, aortic homografts, biocompatible elastomers, and the like which are intended for invasive, or in-dwelling use in a human or animal body. Simple incubation of the natural bioprosthetic materials in an aluminum ion-containing solution, such as aqueous AlCl.sub.3, prior to implantation has been found to inhibit calcification of the biomaterial over a prolonged period and to do so without adverse side effects. Incorporation of an aluminum-containing compound into the formulation for polymers, such as polyurethane, has also been found to inhibit calcification with no adverse side effects.

    摘要翻译： 天然或合成的生物假体材料用三价铝阳离子处理以防止体内钙化。 这样的生物假体材料包括旨在用于人或动物体内的侵入性或住宅用的猪主动脉瓣瓣叶，牛心包膜，主动脉同种异体移植物，生物相容性弹性体等。 已经发现在植入之前，在含铝离子的溶液（例如AlCl 3水溶液）中简单温育天然生物假体材料能够在长时间内抑制生物材料的钙化，并且在没有不利副作用的情况下进行。 也已经发现将含铝化合物掺入聚合物如聚氨酯的制剂中可抑制钙化而没有不利的副作用。

    Design of Hydrolytically Releasable Prodrugs for Sustained Release Nanoparticle Formulations
    5.
    发明申请
    Design of Hydrolytically Releasable Prodrugs for Sustained Release Nanoparticle Formulations 有权
    用于缓释纳米颗粒配方的水解可释放前药的设计

    公开(公告)号：US20130296285A1

    公开(公告)日：2013-11-07

    申请号：US13976776

    申请日：2011-12-28

    申请人： Ivan Alferiev ,  Michael Chorny ,  Robert J. Levy

    发明人： Ivan Alferiev ,  Michael Chorny ,  Robert J. Levy

    IPC分类号： A61K47/48

    CPC分类号： A61K47/48123 ,  A61K47/551 ,  A61K47/554 ,  A61K47/645 ,  C08B37/0021

    摘要： A prodrug according to formula (I) wherein R2 is a residue of a drug, said drug having a hydroxyl group by which the COOR2 group is formed; Z is O or NH; m is 0 or 1; and R3 is an organic moiety comprising a lipophilic group or a residue of a polymer, provided that Z is 0 if the polymer is carboxymethyl dextran. A system includes a plurality of magnetic nanoparticles including a prodrug as described above, a stent and a source of uniform magnetic field capable of producing temporary magnetization of the stent and/or the magnetic nanoparticles. A method of treating a medical condition with a drug includes administering to a patient in need of the drug a prodrug as described above, the prodrug being capable of releasing the drug in the patient after the administration step.

    摘要翻译： 根据式（I）的前药，其中R2是药物的残基，所述药物具有形成COOR 2基团的羟基; Z是O或NH; m为0或1; 并且R3是包含亲油基团或聚合物残基的有机部分，条件是如果聚合物是羧甲基葡聚糖，则Z为0。 一种系统包括多个磁性纳米颗粒，包括如上所述的前体药物，能够产生支架和/或磁性纳米颗粒的暂时磁化的支架和均匀磁场源。 用药物治疗医学病症的方法包括向需要该药物的患者施用如上所述的前药，该前药能够在施用步骤后释放患者的药物。

    Magnetically-driven biodegradable gene delivery nanoparticles formulated with surface-attached polycationic complex
    7.
    发明授权
    Magnetically-driven biodegradable gene delivery nanoparticles formulated with surface-attached polycationic complex 有权
    用表面附着的聚阳离子络合物配制的磁驱动的可生物降解的基因递送纳米颗粒

    公开(公告)号：US07846201B2

    公开(公告)日：2010-12-07

    申请号：US11250948

    申请日：2005-10-14

    申请人： Michael Chorny ,  Boris Polyak ,  Ilia Fishbein ,  Ivan Alferiev ,  Robert J. Levy

    发明人： Michael Chorny ,  Boris Polyak ,  Ilia Fishbein ,  Ivan Alferiev ,  Robert J. Levy

    IPC分类号： A61F2/02

    CPC分类号： A61K9/5146 ,  A61K9/5094 ,  A61K9/5153 ,  A61K47/59 ,  A61K47/6923 ,  A61K47/6929

    摘要： A particle including a matrix-forming agent and a polyelectrolyte-amphiphilic agent adduct wherein the polyelectrolyte-amphiphilic agent adduct is in physical communication with the matrix-forming agent. The particle further includes a coated magnetic field-responsive agent and a biomaterial. Methods of making the particle are provided. Also provided are methods of delivery of the biomaterial to a target cell or a target tissue including administering the particle having the matrix-forming agent, polyelectrolyte-amphiphilic agent adduct, the coated magnetic field-responsive agent and the biomaterial; providing a magnetic device associated with the target cell or the target tissue; applying a magnetic force to the particle; and guiding the particle toward the magnetic device by the magnetic force.

    摘要翻译： 包括基质形成剂和聚电解质 - 两亲加合物的颗粒，其中聚电解质 - 两亲性加合物与基质形成剂物理连通。 颗粒还包括涂覆的磁场响应剂和生物材料。 提供制造颗粒的方法。 还提供了将生物材料递送到靶细胞或靶组织的方法，包括施用具有基质形成剂的颗粒，聚电解质 - 两亲剂加合物，包被的磁场响应剂和生物材料; 提供与所述靶细胞或所述靶组织相关联的磁性装置; 向颗粒施加磁力; 并通过磁力将粒子引向磁性装置。

    Magnetic Gradient Targeting And Sequestering Of Therapeutic Formulations And Therapeutic Systems Thereof
    8.
    发明申请
    Magnetic Gradient Targeting And Sequestering Of Therapeutic Formulations And Therapeutic Systems Thereof 审中-公开
    治疗配方及其治疗系统的磁性梯度靶向和螯合

    公开(公告)号：US20090216320A1

    公开(公告)日：2009-08-27

    申请号：US12297971

    申请日：2007-04-20

    申请人： Robert J. Levy ,  Ivan Alferlev ,  Michael Chorny ,  Ilia Fishbein ,  Gennady Friedman ,  Boris Polyak ,  Darryl Williams

    发明人： Robert J. Levy ,  Ivan Alferlev ,  Michael Chorny ,  Ilia Fishbein ,  Gennady Friedman ,  Boris Polyak ,  Darryl Williams

    IPC分类号： A61M37/00 ,  A61N2/00 ,  A61F2/82

    CPC分类号： A61K9/0009 ,  A61B2017/00876 ,  A61B2017/00893 ,  A61K9/0019 ,  A61L31/14 ,  A61L31/16 ,  A61L2300/624 ,  A61L2400/12 ,  A61N2/002 ,  A61N2/06

    摘要： A therapeutic system and a method that uses stents, and/or other implantable devices (104) for local delivery of a therapeutic agent is disclosed. A therapeutic formulation (102) may include particles of a biocompatible magnetic or magnetizable material that carry the therapeutic agent, or magnetically responsive cells. The therapeutic formulation (102) is intravenously administered to a mammalian subject. A portion of the formulation (102) is delivered to the proximity of a device (104) implanted in the vascular system of the subject by externally generating a magnetic field gradient (106) on the implantable device (104). The portion of the therapeutic formulation (102) not delivered to the proximity of the implantable device (104) is removed from the vascular system. The method allows for the repeated administration of the same or different therapeutic agent, and further, has the option of locally injecting, or alternatively, peripherally administering, the therapeutic agent.

    摘要翻译： 公开了一种治疗系统和使用支架的方法，和/或用于局部递送治疗剂的其它可植入装置（104）。 治疗剂（102）可以包括携带治疗剂或磁反应性细胞的生物相容性磁性或可磁化材料的颗粒。 将治疗制剂（102）静脉内施用于哺乳动物受试者。 制剂（102）的一部分通过在可植入装置（104）上外部产生磁场梯度（106）而输送到植入受试者的血管系统中的装置（104）附近。 从血管系统中去除未被输送到可植入装置（104）附近的部分治疗剂（102）。 该方法允许相同或不同的治疗剂的重复给药，此外，还可以选择局部注射或替代地外周施用治疗剂。

    Thiol activation of polyurethanes and methods of making the same
    9.
    发明授权
    Thiol activation of polyurethanes and methods of making the same 有权
    聚氨酯的硫醇活化及其制备方法

    公开(公告)号：US06890998B2

    公开(公告)日：2005-05-10

    申请号：US10672893

    申请日：2003-09-26

    申请人： Ivan Alferiev ,  Ilia Fishbein ,  Robert J. Levy

    发明人： Ivan Alferiev ,  Ilia Fishbein ,  Robert J. Levy

    IPC分类号： A61L27/18 ,  A61L29/06 ,  A61L31/06 ,  C08G18/44 ,  C08G18/48 ,  C08G18/81 ,  C08G18/82 ,  C08G18/83 ,  G01N21/64

    CPC分类号： A61L27/18 ,  A61L29/06 ,  A61L31/06 ,  C08G18/44 ,  C08G18/4854 ,  C08G18/838 ,  G01N21/6428 ,  C08L75/04

    摘要： A polyurethane having a thiol substituent pendant from at least one nitrogen and/or at least one carbon atom of the polyurethane.A polyurethane having a thiol substituent pendant from at least one nitrogen and/or at least one carbon atom of the polyurethane, wherein the thiol substituent has a formula: —RL—(S—R1)n wherein n is an integer from 1 to 3; RL is an (n+1)-valent organic radical having at least one carbon atom; and R1 is a member selected from the group consisting of H, C(O)R3, and SR4, wherein R3 is a member selected from the group consisting of C1 to C6 alkyl and R4 is a heterocyclic group or an electron deficient aromatic group.

    摘要翻译： 具有聚氨酯的至少一个氮原子和/或至少一个碳原子的硫醇取代基的聚氨酯。 聚氨酯，其具有来自聚氨酯的至少一个氮原子和/或至少一个碳原子的硫醇取代基，其中所述硫醇取代基具有下式：<？in-line-formula description =“In-line Formulas”end =“ （“1”）在线公式描述=“在线公式”结束 =“尾”→其中n是1至3的整数; R L是具有至少一个碳原子的（n + 1）价有机基团; 和R 1是选自H，C（O）R 3和SR 4的成员，其中R SUP > 3 是选自C 1至C 6烷基的基团，R 4是杂环基或 电子缺乏芳族基团。