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21. 发明授权

US09233163B2 Hydrolytically releasable prodrugs for sustained release nanoparticle formulations 有权
标题翻译：用于缓释纳米颗粒制剂的水解可释放的前药
公开(公告)号：US09233163B2
公开(公告)日：2016-01-12
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 , C08B37/02
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。

22. 发明授权

US08562505B2 Uniform field magnetization and targeting of therapeutic formulations 有权
公开(公告)号：US08562505B2
公开(公告)日：2013-10-22
申请号：US12150864
申请日：2008-05-01
申请人： Robert J. Levy , Boris Polyak , Michael Chorny , Ivan Alferiev , Gennady Friedman , Darryl Williams , Ilia Fishbein
发明人： Robert J. Levy , Boris Polyak , Michael Chorny , Ivan Alferiev , Gennady Friedman , Darryl Williams , Ilia Fishbein
IPC分类号： A61N2/10
CPC分类号： A61K41/00 , A61K9/5094 , A61K9/5115 , A61K9/5123 , A61K9/5146 , A61K9/5153 , A61K9/5169 , A61K9/5192 , A61K31/203 , A61K31/337 , A61K31/713 , A61K35/44 , A61K35/761 , A61K47/42 , A61K47/59 , A61K47/6455 , A61K47/6923 , A61K47/6929 , A61K48/0008 , A61K48/0041 , A61K48/0083 , C12N15/111 , C12N15/86 , C12N2320/32 , C12N2710/10343 , C12N2710/10345
摘要： Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Also provided are bioresorbable nanoparticles prepared without the use of organic solvents, and methods for therapeutically using such bioresorbable nanoparticles.

23. 发明申请

US20130243862A1 PHOTOCHEMICAL ACTIVATION OF SURFACES FOR ATTACHING BIOMATERIAL 审中-公开
标题翻译：用于连接生物材料的表面的光化学活化
公开(公告)号：US20130243862A1
公开(公告)日：2013-09-19
申请号：US13606672
申请日：2012-09-07
申请人： Ivan Alferiev , Ilia Fishbein , Michael Chorny , Robert J. Levy , Benjamin Yellen , Darryl Williams
发明人： Ivan Alferiev , Ilia Fishbein , Michael Chorny , Robert J. Levy , Benjamin Yellen , Darryl Williams
IPC分类号： A61L27/16 , C08F120/06 , A61L27/54 , C08F126/02
CPC分类号： A61L27/16 , A61K31/765 , A61K31/785 , A61L27/50 , A61L27/54 , A61L2400/18 , B01J2219/00637 , B01J2219/00648 , C07K17/02 , C07K17/06 , C08F8/10 , C08F8/32 , C08F8/34 , C08F120/06 , C08F126/02 , C08F226/02 , C08F271/02 , C08F290/00 , C08F291/00 , C08G63/91 , C08J7/18 , C08L75/04
摘要： A water-soluble photo-activatable polymer including: a photo-activatable group adapted to be activated by an irradiation source and to form a covalent bond between the water-soluble photo-activatable polymer and a matrix having at least one carbon; a reactive group adapted to covalently react with a biomaterial for subsequent delivery of the biomaterial to a cell; a hydrophilic group; and a polymer precursor. A composition including a monomolecular layer of the water-soluble photo-activatable polymer and a matrix having at least one carbon, wherein the monomolecular layer is covalently attached to the matrix by a covalent bond between the photo-activatable group and the at least one carbon. The composition further includes a biomaterial having a plurality of active groups, wherein the biomaterial is covalently attached to the monomolecular layer by covalent bonding between the active groups and reactive groups. Also provided is a method for delivery of a biomaterial to a cell.
摘要翻译：一种水溶性可光活化聚合物，其包括：适于被辐照源活化并在所述水溶性可光活化聚合物与具有至少一个碳的基质之间形成共价键的可光致活化基团; 适于与生物材料共价反应的反应性基团，用于随后将生物材料递送至细胞; 亲水基团; 和聚合物前体。一种组合物，其包含水溶性可光活化聚合物的单分子层和具有至少一个碳的基质，其中单分子层通过可光致活化基团和至少一个碳之间的共价键共价连接到基质上。组合物还包括具有多个活性基团的生物材料，其中生物材料通过活性基团和反应性基团之间的共价键共价连接到单分子层上。还提供了将生物材料递送到细胞的方法。

24. 发明申请

US20120141419A1 Biodegradable Linkers for Molecular Therapies 有权
标题翻译：用于分子疗法的生物可降解接头
公开(公告)号：US20120141419A1
公开(公告)日：2012-06-07
申请号：US13306459
申请日：2011-11-29
申请人： Ivan Alferiev , Robert J. Levy , Ilia Fishbein
发明人： Ivan Alferiev , Robert J. Levy , Ilia Fishbein
IPC分类号： A61K48/00 , A61K38/44 , A61P9/00 , C12N15/861
CPC分类号： A61K47/6957 , A61K47/6901 , C12N2799/022
摘要： A method and a composition for delivery of a biomaterial to an animal cell or a tissue, the composition includes (a) a biomaterial; (b) a biodegradable cross-linker portion having a hydrolyzable bond, wherein the biodegradable cross-linker portion is covalently bound to the biomaterial; and (c) a substrate, wherein the substrate is covalently bound to the biodegradable cross-linker portion, provided that the biodegradable cross-linker is adapted to hydrolyze by breaking the hydrolyzable bond and thereby release and deliver the biomaterial. A process of making the composition is also provided.
摘要翻译：用于将生物材料递送到动物细胞或组织的方法和组合物，所述组合物包括（a）生物材料; （b）具有可水解键的可生物降解的交联剂部分，其中所述可生物降解的交联剂部分与所述生物材料共价结合; 并且（c）底物，其中所述底物共价结合到所述可生物降解的交联剂部分，条件是所述可生物降解的交联剂适于通过破坏所述可水解键从而水解，从而释放和递送所述生物材料。还提供了制备组合物的方法。

25. 发明申请

US20110076767A1 MAGNETICALLY-DRIVEN BIODEGRADABLE GENE DELIVERY NANOPARTICLES FORMULATED WITH SURFACE-ATTACHED POLYCATIONIC COMPLEX 审中-公开
标题翻译：用表面附着的聚合复合物制备的磁性可驱动的可生物降解的基因递送纳米颗粒
公开(公告)号：US20110076767A1
公开(公告)日：2011-03-31
申请号：US12960968
申请日：2010-12-06
申请人： Michael Chrony , Boris Polyak , Ilia Fishbein , Ivan Alferiev , Robert J. Levy
发明人： Michael Chrony , Boris Polyak , Ilia Fishbein , Ivan Alferiev , Robert J. Levy
IPC分类号： C12N5/071 , H01F1/26
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。

26. 发明授权

US06900282B2 Derivatized polyurethane compositions which exhibit enhanced stability in biological systems and methods of making the same 失效
标题翻译：在生物系统中表现出增强的稳定性的衍生的聚氨酯组合物及其制备方法
公开(公告)号：US06900282B2
公开(公告)日：2005-05-31
申请号：US10672892
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： C08G20060101 , C08G18/48 , C08G18/66 , C08G18/83 , G01N21/64 , C08G18/30
CPC分类号： C08G18/4854 , C08G18/6674 , C08G18/834 , C08G18/836 , C08G18/838
摘要： A process for preparing the polyurethane derivative, the process including: providing a polyurethane having a urethane amino moiety, providing a multifunctional linker reagent of a formula: LG-RL-(FG)n, wherein n is an integer from 1 to 3, FG is a functional group, which is a halogen, a carboxyl group, a sulfonate ester, or an epoxy group, LG is a leaving group, which is a halogen, a carboxyl group, a sulfonate ester, or an epoxy group, and RL is an (n+1)-valent organic radical having at least one carbon atom; providing a protected thiol-containing reagent of a formula R—C(O)SH, or a salt thereof, wherein R is a C1 to C6 alkyl group; reacting the multifunctional linker reagent with the urethane amino moiety to form a polyurethane substituted with at least one substituent group of a formula: —RL-(FG)n; reacting the polyurethane with a protected thiol-containing reagent to form the polyurethane derivative.
摘要翻译：一种制备聚氨酯衍生物的方法，该方法包括：提供具有氨基甲酸酯氨基部分的聚氨酯，提供下式的多官能接头试剂：（R） - （FG）n / SUB，其中n为1至3的整数，FG为卤素，羧基，磺酸酯或环氧基的官能团，LG为离去基团，其为卤素，羧基，磺酸酯或环氧基，R L是具有至少一个碳原子的（n + 1）价有机基团; 提供式R-C（O）SH或其盐的受保护的含硫醇的试剂，其中R是C 1至C 6烷基; 使多官能接头试剂与氨基甲酸酯氨基部分反应以形成由至少一个下式的取代基取代的聚氨酯：（R） - （FG）n < 使聚氨酯与被保护的含硫醇的试剂反应以形成聚氨酯衍生物。

27. 发明授权

US09694103B2 Photochemical activation of surfaces for attaching biomaterial 有权
公开(公告)号：US09694103B2
公开(公告)日：2017-07-04
申请号：US13606672
申请日：2012-09-07
申请人： Ivan Alferiev , Ilia Fishbein , Michael Chorny , Robert J. Levy , Benjamin Yellen , Darryl Williams
发明人： Ivan Alferiev , Ilia Fishbein , Michael Chorny , Robert J. Levy , Benjamin Yellen , Darryl Williams
IPC分类号： A61K9/00 , A61L27/16 , C08F126/02 , C08F120/06 , A61L27/54 , A61L27/50 , A61K31/765 , A61K31/785 , C07K17/02 , C08F226/02 , C08J7/18 , C08F271/02 , C08F290/00 , C08F291/00 , C08G63/91 , C08L75/04 , C07K17/06
CPC分类号： A61L27/16 , A61K31/765 , A61K31/785 , A61L27/50 , A61L27/54 , A61L2400/18 , B01J2219/00637 , B01J2219/00648 , C07K17/02 , C07K17/06 , C08F8/10 , C08F8/32 , C08F8/34 , C08F120/06 , C08F126/02 , C08F226/02 , C08F271/02 , C08F290/00 , C08F291/00 , C08G63/91 , C08J7/18 , C08L75/04
摘要： A water-soluble photo-activatable polymer including: a photo-activatable group adapted to be activated by an irradiation source and to form a covalent bond between the water-soluble photo-activatable polymer and a matrix having at least one carbon; a reactive group adapted to covalently react with a biomaterial for subsequent delivery of the biomaterial to a cell; a hydrophilic group; and a polymer precursor. A composition including a monomolecular layer of the water-soluble photo-activatable polymer and a matrix having at least one carbon, wherein the monomolecular layer is covalently attached to the matrix by a covalent bond between the photo-activatable group and the at least one carbon. The composition further includes a biomaterial having a plurality of active groups, wherein the biomaterial is covalently attached to the monomolecular layer by covalent bonding between the active groups and reactive groups. Also provided is a method for delivery of a biomaterial to a cell.

28. 发明授权

US08084435B2 Biodegradable linkers for molecular therapies 有权
标题翻译：用于分子疗法的生物可降解接头
公开(公告)号：US08084435B2
公开(公告)日：2011-12-27
申请号：US11799861
申请日：2007-05-03
申请人： Ivan Alferiev , Robert J. Levy , Ilia Fishbein
发明人： Ivan Alferiev , Robert J. Levy , Ilia Fishbein
IPC分类号： A61K31/70 , C12N11/06 , C12N11/00 , A01N43/04 , A61F2/00
CPC分类号： A61K47/6957 , A61K47/6901 , C12N2799/022
摘要： A method and a composition for delivery of a biomaterial to an animal cell or a tissue, the composition includes (a) a biomaterial; (b) a biodegradable cross-linker portion having a hydrolyzable bond, wherein the biodegradable cross-linker portion is covalently bound to the biomaterial; and (c) a substrate, wherein the substrate is covalently bound to the biodegradable cross-linker portion, provided that the biodegradable cross-linker is adapted to hydrolyze by breaking the hydrolyzable bond and thereby release and deliver the biomaterial. A process of making the composition is also provided.
摘要翻译：用于将生物材料递送到动物细胞或组织的方法和组合物，所述组合物包括（a）生物材料; （b）具有可水解键的可生物降解的交联剂部分，其中所述可生物降解的交联剂部分与所述生物材料共价结合; 并且（c）底物，其中所述底物共价结合到所述可生物降解的交联剂部分，条件是所述可生物降解的交联剂适于通过破坏所述可水解键从而水解，从而释放和递送所述生物材料。还提供了制备组合物的方法。

29. 发明授权

US07589070B2 Surface modification for improving biocompatibility 有权
标题翻译：改善生物相容性的表面改性
公开(公告)号：US07589070B2
公开(公告)日：2009-09-15
申请号：US10170411
申请日：2002-06-14
申请人： Robert J. Levy , Ivan Alferiev , Cunxian Song , Ilia Fishbein
发明人： Robert J. Levy , Ivan Alferiev , Cunxian Song , Ilia Fishbein
IPC分类号： A61K31/70 , A01N43/04 , A61K39/395 , A61F2/00
CPC分类号： C12N15/87 , A61K38/00 , A61K39/00 , A61K47/69 , A61K48/00
摘要： A therapeutic delivery system efficiently introduces biologically active molecules to mammalian cells without the use of synthetic polymers or biopolymer coatings. Surface modification of a metal support, such as a medical device, results in a single molecular layer that can fasten various molecules, thereby minimizing any cellular inflammatory response while enhancing biocompatibility.
摘要翻译：治疗递送系统在不使用合成聚合物或生物聚合物涂层的情况下有效地将生物活性分子引入哺乳动物细胞。金属载体（例如医疗装置）的表面改性导致单个分子层，其可以固定各种分子，从而最小化任何细胞炎性反应，同时增强生物相容性。

30. 发明授权

US07156881B2 Counteracting bioprosthetic calcification 失效
标题翻译：抵制生物假体钙化
公开(公告)号：US07156881B2
公开(公告)日：2007-01-02
申请号：US10336857
申请日：2003-01-06
申请人： Robert J. Levy , Ivan Alferiev
发明人： Robert J. Levy , Ivan Alferiev
IPC分类号： A61F2/02
CPC分类号： A61K31/663 , A61L27/3687 , A61L27/54 , A61L31/16 , A61L2400/02
摘要： Adapting crosslinking with triglycidyl amine (TGA) to incorporate the use of a particular type of anti-calcification agent provides a broad-reaching solution to the problem in vivo bioprosthesis calcification. The anti-calcification agent in question includes a polyphosphonate compound that contains a functional group, which serves as a reaction site between the polyphosphonate and a polyepoxide. The functional group is reactive enough to dominate the reaction between the polyphosphonate and the polyepoxide, thereby excluding the chelating oxygen atoms of polyphosphonate from the reaction, protecting their anti-calcification ability. Furthermore, the high reactivity of the functional group allows the polyphosphonate to attach to the polyepoxide more completely, which improves the calcification resistance of bioprosthetic material with which the polyepoxide is crosslinked.
摘要翻译：使用三缩水甘油胺（TGA）进行交联以引入特定类型的抗钙化剂的使用为体内生物假体钙化提供了广泛的解决方案。所讨论的抗钙化剂包括含有官能团的聚膦酸酯化合物，其用作聚膦酸盐和聚环氧化物之间的反应位点。官能团反应性足以支配聚膦酸酯与聚环氧化物之间的反应，从反应中排除多膦酸的螯合氧原子，保护其抗钙化能力。此外，官能团的高反应性允许聚膦酸盐更加完全地附着到聚环氧化物上，这提高了聚环氧化物交联的生物纤维材料的耐钙性。

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