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1. 发明授权

US07179487B1 Hydrogels of water soluble polymers crosslinked by protein domains 有权
标题翻译：由蛋白质结构域交联的水溶性聚合物的水凝胶
公开(公告)号：US07179487B1
公开(公告)日：2007-02-20
申请号：US09336259
申请日：1999-06-18
申请人： Jindrich Kopecek , Russell Stewart , Karin Caldwell , Chung Wang , Chih-Hu Ho
发明人： Jindrich Kopecek , Russell Stewart , Karin Caldwell , Chung Wang , Chih-Hu Ho
IPC分类号： A61K9/00 , A61K38/03 , A61K38/16
CPC分类号： A61K9/06 , A61K38/00 , A61K47/42
摘要： A stimuli-responsive, hybrid hydrogel wherein the bulk of the polymer is made up of relatively inexpensive water soluble polymer strands crosslinked by protein domains. The responsiveness of the gel is controlled or modulated by the protein component.The physical and biological properties of the hydrogel are determined by specifically designed or engineered protein domains.The crosslinking of the protein domains to the water soluble polymers is by means of non-covalent bonding such as chelation or coordination bonding, biotin-avidin bonding, protein—protein interaction and protein-ligand interaction, or by means of covalent bonding. Methods of making and using the polymer-protein hydrogels are disclosed in this application.
摘要翻译：一种刺激响应性混合型水凝胶，其中大部分聚合物由相对便宜的由蛋白质结构域交联的水溶性聚合物链构成。凝胶的响应性由蛋白质组分控制或调节。水凝胶的物理和生物学性质通过专门设计或改造的蛋白质结构域来确定。蛋白质结构域与水溶性聚合物的交联是通过非共价键合，例如螯合或配位键合，生物素 - 抗生物素蛋白键合，蛋白质 - 蛋白质相互作用和蛋白质 - 配体相互作用，或通过共价键。在本申请中公开了制备和使用聚合物 - 蛋白质水凝胶的方法。

2. 发明授权

US10092662B2 Macromolecular delivery systems for non-invasive imaging, evaluation and treatment of arthritis and other inflammatory diseases 有权
公开(公告)号：US10092662B2
公开(公告)日：2018-10-09
申请号：US10591258
申请日：2005-03-30
申请人： Dong Wang , Jindrich Kopecek , Scott C. Miller , Pavla Kopeckova
发明人： Dong Wang , Jindrich Kopecek , Scott C. Miller , Pavla Kopeckova
IPC分类号： A61K47/58 , A61K49/00 , A61K49/12
摘要： This invention relates to biotechnology, more particularly, to water-soluble polymeric delivery systems for the imaging, evaluation and/or treatment of rheumatoid arthritis and other inflammatory diseases. Using modern MR imaging techniques, the specific accumulation of macromolecules in arthritic joints in adjuvant-induced arthritis in rats is demonstrated. The strong correlation between the uptake and retention of the MR contrast agent labeled polymer with histopathological features of inflammation and local tissue damage demonstrates the practical applications of the macromolecular delivery system of the invention.

3. 发明申请

US20110085979A1 CONJUGATE OF A POLYMER, AN ANTI-ANGIOGENESIS AGENT AND A TARGETING MOIETY, AND USES THEREOF IN THE TREATMENT OF BONE RELATED ANGIOGENESIS CONDITIONS 有权
标题翻译：聚合物，抗血管发生剂和靶向药物的联合使用及其在治疗骨髓相关血管生成条件中的应用
公开(公告)号：US20110085979A1
公开(公告)日：2011-04-14
申请号：US12993855
申请日：2009-05-21
申请人： Ronit Satchi-Fainaro , Ehud Segal , Jindrich Kopecek , Pavla Kopeckova , Huaizhong Pan
发明人： Ronit Satchi-Fainaro , Ehud Segal , Jindrich Kopecek , Pavla Kopeckova , Huaizhong Pan
IPC分类号： A61K49/00 , A61K31/787 , A61P35/00 , A61P19/08 , C08F8/40 , A61P35/04 , C07K17/10 , C07K17/08
CPC分类号： A61K47/48176 , A61K31/787 , A61K47/58 , A61K49/0043 , A61K49/0054
摘要： Conjugates of hydroxypropyl methacrylamide (HPMA)-derived copolymers having attached thereto TNP-470 and a high load (e.g., higher than 3 mol %) of alendronate (ALN), and processes of preparing same are disclosed.Conjugates of polymers or copolymers having attached thereto an anti-angiogenesis agent and an oligoaspartate bone targeting agent, and processes of preparing same, are further disclosed.Pharmaceutical compositions containing these conjugates and uses thereof in the treatment and monitoring of bone related disorders are also disclosed.
摘要翻译：公开了具有附着于其上的羟丙基甲基丙烯酰胺（HPMA）衍生的共聚物TNP-470和高负载量（例如高于3mol％）的阿仑膦酸盐（ALN）的结合物及其制备方法。另外还公开了附着有抗血管生成剂和寡天冬氨酸骨靶向剂的聚合物或共聚物的共轭物及其制备方法。还公开了含有这些缀合物的药物组合物及其在骨相关疾病的治疗和监测中的用途。

4. 发明授权

US4074039A Hydrophilic N,N-diethyl acrylamide copolymers 失效
标题翻译：亲水性N，N-二乙基丙烯酰胺共聚物
公开(公告)号：US4074039A
公开(公告)日：1978-02-14
申请号：US657602
申请日：1976-02-12
申请人： Drahoslav Lim , Jindrich Kopecek , Hedvika Bazilova nee Sverinova , Jiri Vacik
发明人： Drahoslav Lim , Jindrich Kopecek , Hedvika Bazilova nee Sverinova , Jiri Vacik
IPC分类号： A61L27/16 , C08F20/52 , C08F20/54 , C08F220/54
CPC分类号： C08F20/52 , A61L27/16 , C08F20/54
摘要： There is disclosed a hydrophilic gel suitable for exposure to repeated long-term contact with live tissues or mucous membranes and consisting of macromolecules obtained by polymerizing a mixture of at least two copolymerizable units and a crosslinking agent. The mixture consists of from 52 to 99.5 parts by weight of N,N-diethylacrylamide, 43 to 0.1 parts by weight of a member selected from the group consisting of N,N-dialkyl acrylamide, N-alkyl methacrylamide, nitriles of acrylic and methacrylic acids and from 5 to 0.4 parts by of a divinylic monomer selected from the group consisting of diesters of acrylic acid and methacrylic acid, and methylene or ethylene-bis-methacrylamide or acrylamide.
摘要翻译：公开了适于暴露于与活组织或粘膜重复长期接触的亲水性凝胶，并且由通过聚合至少两种可共聚单元和交联剂的混合物获得的大分子组成。该混合物由52至99.5重量份的N，N-二乙基丙烯酰胺，43至0.1重量份的选自N，N-二烷基丙烯酰胺，N-烷基甲基丙烯酰胺，丙烯酸和甲基丙烯酸腈酸和5至0.4份的选自丙烯酸和甲基丙烯酸的二酯和亚甲基或亚乙基 - 双 - 甲基丙烯酰胺或丙烯酰胺的二乙烯基单体。

5. 发明授权

US10279044B2 Bone fracture repair by targeting of agents that promote bone healing 有权
$Bone fracture repair by targeting of agents that promote bone healing$
公开(公告)号：US10279044B2
公开(公告)日：2019-05-07
申请号：US15578226
申请日：2016-05-29
申请人： Purdue Research Foundation Office of Technology Commercialization , University of Utah Research Foundation , Jindrich Kopecek , Jiyan Yang
发明人： Stewart Andrew Low , Philip S. Low , Christopher Galliford , Jindrich Kopecek , Jiyan Yang
IPC分类号： A61K31/404 , C07D403/04 , C07D209/34 , C07D487/00 , A61K47/42 , A61L27/22 , A61L27/54 , C07K7/06 , C07K7/08 , A61P19/00 , A61K9/107 , A61M5/00
摘要： Aspects of the present disclosure generally relate to compounds for targeting and healing bone fractures. Some of these compounds include a negatively charged oligopeptide comprising an acidic oligopeptide, a linker, which may be hydrolyzable or may be a substrate for the protease cathepsin K, and at least one molecule that promotes bone healing. In some compounds the molecule that promotes bone healing is an anabolic compound that inhibits GSK3β, in some compounds the molecule that promotes the healing of bone fracture is a pro-inflammatory agent such as PGE1. Other embodiments include methods of treating a bone fracture comprising administering a therapeutic amount of any one of the compounds disclosed herein.

6. 发明申请

US20080159959A1 Macromolecular Delivery Systems for Non-Invasive Imaging, Evaluation and Treatment of Arthritis and Other Inflammatory Diseases 审中-公开
标题翻译：用于非侵入性成像，评估和治疗关节炎和其他炎症疾病的大分子递送系统
公开(公告)号：US20080159959A1
公开(公告)日：2008-07-03
申请号：US10591258
申请日：2005-03-30
申请人： Dong Wang , Jindrich Kopecek , Scott C. Miller , Pavla Kopeckova
发明人： Dong Wang , Jindrich Kopecek , Scott C. Miller , Pavla Kopeckova
IPC分类号： A61K47/48 , A61K47/30 , A61K38/02 , A61K31/44 , A61K38/13 , A61K33/34 , A61K49/12 , A61P29/00 , A61K49/00 , A61K33/24 , A61K31/197 , A61K31/519 , A61K47/38
CPC分类号： A61K49/0054 , A61K47/58 , A61K49/0041 , A61K49/128
摘要： This invention relates to biotechnology, more particularly, to water-soluble polymeric delivery systems for the imaging, evaluation and/or treatment of rheumatoid arthritis and other inflammatory diseases. Using modern MR imaging techniques, the specific accumulation of macromolecules in arthritic joints in adjuvant-induced arthritis in rats is demonstrated. The strong correlation between the uptake and retention of the MR contrast agent labeled polymer with histopathological features of inflammation and local tissue damage demonstrates the practical applications of the macromolecular delivery system of the invention.
摘要翻译：本发明涉及生物技术，更具体地涉及用于成像，评估和/或治疗类风湿性关节炎和其它炎性疾病的水溶性聚合物递送系统。使用现代MR成像技术，证明了大鼠在佐剂诱导的关节炎中关节炎关节中大分子的特异性积累。 MR造影剂标记的聚合物的吸收和保留与炎症和局部组织损伤的组织病理特征之间的强相关性证明了本发明的大分子递送系统的实际应用。

7. 发明授权

US5415864A Colonic-targeted oral drug-dosage forms based on crosslinked hydrogels containing azobonds and exhibiting PH-dependent swelling 失效
标题翻译：基于含有偶联物的交联水凝胶并显示出PH依赖性肿胀的结肠靶向口服药物剂型
公开(公告)号：US5415864A
公开(公告)日：1995-05-16
申请号：US932914
申请日：1992-08-20
申请人： Jindrich Kopecek , Sung W. Kim , Helle Brondsted , Pavla Kopeckova
发明人： Jindrich Kopecek , Sung W. Kim , Helle Brondsted , Pavla Kopeckova
IPC分类号： A61K9/20 , A61K47/32 , A61K47/48 , C08F20/02 , C08F20/26 , C08F20/34 , C08F20/42 , C08F20/52 , C08F26/10 , C08F212/00 , C08F212/12 , C08F218/02 , C08F218/08 , C08F220/04 , C08F220/06 , C08F220/28 , C08F220/36 , C08F220/46 , C08F220/58 , C08F220/60 , C08F222/06 , C08F226/10 , C08F246/00 , C08L31/04 , C08L33/00 , C08L33/04 , A61K9/48 , A61F9/02
CPC分类号： C08F246/00 , A61K47/32 , A61K47/48176 , A61K9/2027
摘要： Colonic-targeted oral drug dosage forms composed of a drug confined within a crosslinked hydrogel that exhibits pH-dependent swelling and is composed of an ionizable comonomer such as acrylic acid, a nonionizable comonomer such as an acrylamide, and a crosslinking agent that contains an aromatic azobond. Selective drug release in the colon occurs by a combination of pH-dependent swelling of the hydrogel and degradation of the hydrogel by enzymatic cleavage of the azobonds by azoreductases.
摘要翻译：由限制在交联水凝胶内的药物组成的结肠靶向口服药物剂型，其表现出pH依赖性溶胀并且由可离子化的共聚单体如丙烯酸，不可分解的共聚单体如丙烯酰胺和含有芳族化合物的交联剂组成偶氮结肠中的选择性药物释放通过水凝胶的pH依赖性溶胀和水解凝胶的降解的组合发生，通过偶氮氧化酶的酶切割。

8. 发明授权

US4097470A Preparation of biogically active substances bearing -NH.sub.2 groups in a form releasable by enzymatic cleavage 失效
标题翻译：制备具有-NH（HD 2）（以酶切割释放的形式的B基团）的生物活性物质
公开(公告)号：US4097470A
公开(公告)日：1978-06-27
申请号：US584887
申请日：1975-06-09
申请人： Jaroslav Drobnik , Jindrich Kopecek , Jiri Labsky , Pavla Rejmanova , Josef Exner , Jaroslav Kalal
发明人： Jaroslav Drobnik , Jindrich Kopecek , Jiri Labsky , Pavla Rejmanova , Josef Exner , Jaroslav Kalal
IPC分类号： C08F220/36 , C08F220/60 , C08F16/28 , C08F24/00 , C08F210/00
CPC分类号： C08F220/36 , C08F220/60 , Y10S260/47
摘要： Polymeric form of a biologically active compound containing at least one -NH.sub.2 group in its molecule, adapted for the protracted release of said biologically active compound by enzymatic cleavage of the polymer in vivo in the organism. The active compound is bonded by its -NH.sub.2 group to the carboxylic group of an L-amino acid as for instance, .beta.-phenylalanine, tyrosine, tryptophane, lysine, arginine, glycine, alanine, leucine, citruline or ornithine, which latter is in twin bonded by its amino group to the terminal carboxylic group of the side chain of a substituted amide or ester of acrylic or methacrylic acid, said side chain constituting a linear moiety containing at least 3 carbon atoms. The latter compound or monomer is copolymerized with a hydrophilic monomer such as, N-alkylmethacrylamide, N-alkylacrylamide, N,N-dialkylacrylamide, wherein alkyl has 1-6 carbon atoms and may contain 1 to 3 OH groups, or glycol acrylate or methacrylate alone or in admixture, and which copolymer may contain further monomeric components, for example, cross-linking agents. It is the copolymer which constitutes the subject matter of the invention, i.e., the biologically active substance bearing -NH.sub.2 groups in a form releasable by enzymatic cleavage. The copolymer can also be prepared using as the monomer a compound containing the bonded L-amino acid and in which the terminal carboxylic group has been converted to the reactive ester. The active compound is then bonded to the thusly prepared reactive polymer. The enzymatic release of the active compound bearing -NH.sub.2 groups can be controlled, i.e., regulated by the size of the side chain carrying the L-amino acid.
摘要翻译：在其分子中含有至少一个-NH 2基团的生物活性化合物的聚合形式，适于通过生物体内的体内酶的裂解来延长所述生物活性化合物的释放。活性化合物通过其-NH 2基团与L-氨基酸的羧基键合，例如β-苯丙氨酸，酪氨酸，色氨酸，赖氨酸，精氨酸，甘氨酸，丙氨酸，亮氨酸，柠檬酸或鸟氨酸，后者位于双键通过其氨基键合至取代酰胺或丙烯酸或甲基丙烯酸酯的侧链的末端羧基，所述侧链构成含有至少3个碳原子的直链部分。后一种化合物或单体与亲水性单体如N-烷基甲基丙烯酰胺，N-烷基丙烯酰胺，N，N-二烷基丙烯酰胺共聚合，其中烷基具有1-6个碳原子并且可以含有1至3个OH基团，或二醇丙烯酸酯或甲基丙烯酸酯单独或混合，并且哪种共聚物可以含有其它单体组分，例如交联剂。构成本发明主题的共聚物，即具有可通过酶裂解释放形式的-NH 2基团的生物活性物质。共聚物也可以使用含有键合的L-氨基酸的化合物作为单体制备，并且其中末端羧基已经转化成反应性酯。然后将活性化合物与如此制备的反应性聚合物结合。可以控制带有-NH 2基团的活性化合物的酶促释放，即通过携带L-氨基酸的侧链的大小来调节。

9. 发明授权

US3931123A Hydrophilic nitrite copolymers 失效
标题翻译：水解硝酸酯共聚物
公开(公告)号：US3931123A
公开(公告)日：1976-01-06
申请号：US355496
申请日：1973-04-30
申请人： Jiri Vacik , Jindrich Kopecek
发明人： Jiri Vacik , Jindrich Kopecek
IPC分类号： G02C7/04 , C08F2/04 , C08F20/00 , C08F20/26 , C08F220/00 , C08F220/28 , C08F220/42 , C08F290/00 , C08F299/00 , C08J9/28 , C08F8/42 , C08F16/02
CPC分类号： C08F220/28 , C08F220/42 , Y10S521/905
摘要： A composition of matter with improved mechanical properties which contain 2 - 50 mol. percent of methacrylonitrile or acrylonitrile and 50 - 98 mol. percent of glycol monoesters of acrylic or methacrylic acid, where the glycol is selected from the group comprising ethylene glycol, diethylene glycol, triethylene glycol and their mixtures. 0.1 - 30 mol. percent of the glycol monoesters may be substituted by a crosslinking agent selected from the group comprising 1,4-cyclohexanedimethyl dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, 1,6-hexamethylene-bis-acrylamide, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, methylene-bis-acrylamide, ethylene-bis-acrylamide. Also hydrogen catalysts of compositions bonded to platinum, palladium or rhodium metal.A process for producing the matter, wherein glycol esters of acrylic or methacrylic acid are copolymerized with methacrylonitrile or acrylonitrile, if desired in the presence of a crosslinking agent.

10. 发明申请

US20180147286A1 BONE FRACTURE REPAIR BY TARGETING OF AGENTS THAT PROMOTE BONE HEALING 审中-公开
公开(公告)号：US20180147286A1
公开(公告)日：2018-05-31
申请号：US15578226
申请日：2016-05-29
申请人： Jindrich Kopecek , Jiyan Yang , Purdue Research Foundation Office of Technology Commercialization , University of Utah Research Foundation
发明人： Stewart Andrew Low , Philip S. Low , Christopher Galliford , Jindrich Kopecek , Jiyan Yang
IPC分类号： A61K47/42 , A61M5/00 , A61P19/00 , A61K9/107 , A61K31/404
CPC分类号： A61K47/42 , A61K9/1075 , A61K31/404 , A61L27/22 , A61L27/227 , A61L27/54 , A61L2400/06 , A61L2430/02 , A61M5/002 , A61P19/00 , C07K7/06 , C07K7/08
摘要： Aspects of the present disclosure generally relate to compounds for targeting and healing bone fractures. Some of these compounds include a negatively charged oligopeptide comprising an acidic oligopeptide, a linker, which may be hydrolyzable or may be a substrate for the protease cathepsin K, and at least one molecule that promotes bone healing. In some compounds the molecule that promotes bone healing is an anabolic compound that inhibits GSK3β, in some compounds the molecule that promotes the healing of bone fracture is a pro-inflammatory agent such as PGE1. Other embodiments include methods of treating a bone fracture comprising administering a therapeutic amount of any one of the compounds disclosed herein.

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