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71. 发明授权

US09320760B2 Compositions and methods of use of compounds to increase cancer patient survival time 有权
标题翻译：使用化合物增加癌症患者生存时间的组合物和方法
公开(公告)号：US09320760B2
公开(公告)日：2016-04-26
申请号：US12218470
申请日：2008-07-15
申请人： Frederick H. Hausheer
发明人： Frederick H. Hausheer
IPC分类号： A61K31/095 , A61K33/24 , A61K31/105 , A61K31/282 , A61K31/337 , A61K31/437 , A61K31/505 , A61K31/704 , A61K31/7064 , A61K31/7076 , A61K38/05 , A61K38/06 , A61K45/06 , G01N33/574
CPC分类号： A61K33/24 , A61K31/095 , A61K31/105 , A61K31/282 , A61K31/337 , A61K31/437 , A61K31/505 , A61K31/704 , A61K31/7064 , A61K31/7076 , A61K38/05 , A61K38/06 , A61K45/06 , G01N33/57407 , G01N2333/90212 , A61K2300/00
摘要： The present invention discloses and claims compositions, methods of treatment, and kits which cause an increase in time of survival in cancer patients, wherein the cancer either: (i) overexpresses thioredoxin or glutaredoxin and/or (ii) exhibits evidence of thioredoxin- or glutaredoxin-mediated resistance to one or more chemotherapeutic interventions. The present invention also discloses and claims methods and kits for the administration of said compositions to properly treat cancer patients. Additionally, the present invention discloses and claims methods and kits for quantitatively determining the level of expression of thioredoxin or glutaredoxin in the cancer cells of a cancer patient, methods of using those determined levels in the initial diagnosis and/or planning of subsequent treatment methodologies for said cancer patient, as well as ascertaining the potential growth “aggressiveness” of the particular cancer and treatment responsiveness of the particular type of cancer. Further, the present invention discloses and claims novel pharmaceutical compositions, methods, and kits used for the treatment of patients with medical conditions and disease where there is the overexpression of thioredoxin and/or glutaredoxin, and wherein this overexpression is associated with deleterious physiological effects in the patients.
摘要翻译：本发明公开并要求组合物，治疗方法和试剂盒，其导致癌症患者的存活时间增加，其中所述癌症或者：（i）过表达硫氧还蛋白或谷氧还蛋白和/或（ii）显示硫氧还蛋白或对一种或多种化学治疗干预的谷氧还蛋白介导的抗性。本发明还公开并要求用于施用所述组合物以适当治疗癌症患者的方法和试剂盒。此外，本发明公开并说明了用于定量测定癌症患者癌细胞中硫氧还蛋白或谷氧还蛋白表达水平的方法和试剂盒，在初始诊断和/或规划后续治疗方法中使用确定水平的方法所述癌症患者以及确定特定癌症的潜在增长“侵略性”和特定类型癌症的治疗反应性。此外，本发明公开并要求用于治疗患有硫氧还蛋白和/或谷氧还蛋白过表达的医学病症和疾病的患者的新型药物组合物，方法和试剂盒，并且其中该过表达与有害的生理作用相关病人。

72. 发明授权

US09023805B2 Increasing cancer patient survival time by administration of dithio-containing compounds 有权
标题翻译：通过给予含二硫化合物增加癌症患者的存活时间
公开(公告)号：US09023805B2
公开(公告)日：2015-05-05
申请号：US12807931
申请日：2010-09-16
申请人： Frederick H. Hausheer
发明人： Frederick H. Hausheer
IPC分类号： A61K38/05 , A61K45/06 , A61K31/517 , A61K33/24 , A61K38/21
CPC分类号： A61K45/06 , A61K31/517 , A61K33/24 , A61K38/05 , A61K38/212 , A61K2300/00
摘要： The present invention discloses and claims compositions, methods of treatment, and kits which cause an increase in the time of survival in cancer patients, wherein the cancer: (i) overexpresses thioredoxin or glutaredoxin and/or (ii) exhibits evidence of thioredoxin- or glutaredoxin-mediated resistance to one or more chemotherapeutic interventions. The present invention also discloses and claims methods and kits for the administration of said compositions to properly treat cancer patients. Additionally, the present invention discloses and claims methods and kits for quantitatively determining the level of expression of thioredoxin or glutaredoxin in the cancer cells of a cancer patient, methods of using those determined levels in the initial diagnosis and/or planning of subsequent treatment methodologies for said cancer patient, as well as ascertaining the potential growth “aggressiveness” of the particular cancer and treatment responsiveness of the particular type of cancer. Further, the present invention discloses and claims novel pharmaceutical compositions, methods, and kits used for the treatment of patients with medical conditions and disease where there is the overexpression of thioredoxin and/or glutaredoxin, and wherein this overexpression is associated with deleterious physiological effects in the patients.
摘要翻译：本发明公开并要求组合物，治疗方法和试剂盒，其导致癌症患者生存时间增加，其中癌症：（i）过表达硫氧还蛋白或谷氧还蛋白和/或（ii）显示硫氧还蛋白或对一种或多种化学治疗干预的谷氧还蛋白介导的抗性。本发明还公开并要求用于施用所述组合物以适当治疗癌症患者的方法和试剂盒。此外，本发明公开并说明了用于定量测定癌症患者癌细胞中硫氧还蛋白或谷氧还蛋白表达水平的方法和试剂盒，在初始诊断和/或规划后续治疗方法中使用确定水平的方法所述癌症患者以及确定特定癌症的潜在增长“侵略性”和特定类型癌症的治疗反应性。此外，本发明公开并要求用于治疗患有硫氧还蛋白和/或谷氧还蛋白过表达的医学病症和疾病的患者的新型药物组合物，方法和试剂盒，并且其中该过表达与有害的生理作用相关病人。

73. 发明授权

US08722886B1 Methods for the total chemical synthesis of enantiomerically-pure 7-(2′-trimethylsilyl)ethyl camptothecin 有权
标题翻译：完全化学合成对映体纯7-（2'-三甲基甲硅烷基）乙基喜树碱的方法
公开(公告)号：US08722886B1
公开(公告)日：2014-05-13
申请号：US13694255
申请日：2012-11-13
申请人： Xinghai Chen , Frederick H. Hausheer , Andrey Malakhov , Harry Kochat
发明人： Xinghai Chen , Frederick H. Hausheer , Andrey Malakhov , Harry Kochat
IPC分类号： C07F7/02 , C07D491/147
CPC分类号： C07F7/10 , C07F7/0812
摘要： The present invention discloses and claims five (5) novel, highly efficient synthetic routes for the total synthesis of enantiomerically-pure (i.e., 99%) 7-(2′-trimethylsilyl)ethyl camptothecin (BNP1350; Karenitecin; Cositecan). These aforementioned synthetic schemes are the first to disclose the total syntheses of 7-(2′-trimethylsilyl)ethyl camptothecin using a highly novel direct, non-linear and convergent synthetic strategy which involves annealing the key C7-(trimethylsilyl)ethyl side chain-bearing A ring key synthons to an enantiomerically-pure tricyclic pyridone; rather than through the conventional methodology which incorporates the C7-(trimethylsilyl)ethyl side chain as the final synthetic step on a totally synthesized camptothecin parent compound. The current novel synthetic approaches reported herein since utilize desirably functionalized A-ring with preinstalled trimethyl silyl ethyl side chain, the aforementioned synthetic methodologies have a wider scope of making wide range of pharmaceutically relevant A-ring substituted BNP1350 analogs by substituting desirably functionalized nitro or protected amino phenyl carboxy A-ring as the starting material.
摘要翻译：本发明公开并要求五（5）种用于全合成对映体纯（即99％）7-（2'-三甲基甲硅烷基）乙基喜树碱（BNP1350; Karenitecin; CositECAN））的新型高效合成途径。这些上述合成方案是首先使用高度新颖的直接，非线性和收敛的合成策略来公开7-（2'-三甲基甲硅烷基）乙基喜树碱的总合成，其涉及关键的C7-（三甲基甲硅烷基）乙基侧链 - 带有A对键合物到对映体纯的三环吡啶酮; 而不是通过在全合成的喜树碱母体化合物上结合C7-（三甲基甲硅烷基）乙基侧链作为最终合成步骤的常规方法。由于利用预先安装的三甲基甲硅烷基乙基侧链所需的官能化的A环，本文报道的目前新的合成方法，通过将期望的官能化硝基或被保护的取代基取代了较宽范围的药学上相关的A环取代的BNP1350类似物氨基苯基羧基A环作为起始原料。

74. 发明授权

US08710095B2 Drugs for prophylaxis or mitigation of taxane-induced neurotoxicity 有权
标题翻译：用于预防或缓解紫杉烷诱导的神经毒性的药物
公开(公告)号：US08710095B2
公开(公告)日：2014-04-29
申请号：US10135975
申请日：2002-04-30
申请人： Frederick H. Hausheer
发明人： Frederick H. Hausheer
IPC分类号： A01N43/02 , A61K31/335 , A01N41/02 , A61K31/255
CPC分类号： A61K31/185
摘要： Provided are pharmaceutical drugs for preventing or mitigating adverse actions associated with taxane antineoplastic drugs which are frequently and widely used in cancer chemotherapy, and pharmaceutical compositions which allow us to shorten the duration of treatment with taxane antineoplastic agents and/or to repeat the taxane treatment course more times, as well as drugs suitable for the therapeutic schedules.
摘要翻译：提供了用于预防或减轻与用于癌症化学疗法中经常广泛使用的紫杉类抗肿瘤药物相关的不良反应的药物，以及允许我们缩短用紫杉烷抗肿瘤剂治疗持续时间和/或重复紫杉烷治疗过程的药物组合物更多次，以及适合治疗时间表的药物。

75. 发明申请

US20140073793A1 Germanium-containing camptothecin analogues 审中-公开
标题翻译：含锗喜树碱类似物
公开(公告)号：US20140073793A1
公开(公告)日：2014-03-13
申请号：US13573294
申请日：2012-09-07
申请人： Xinghai Chen , Harry Kochat , Pavankumar N.V. Petluru , Aulma Parker , Frederick H. Hausheer
发明人： Xinghai Chen , Harry Kochat , Pavankumar N.V. Petluru , Aulma Parker , Frederick H. Hausheer
IPC分类号： C07F7/30
CPC分类号： C07F7/30
摘要： The present invention discloses: (i) the novel germanium-containing camptothecin compound, 7[2′-trimethylgermanyl]ethyl-20(S) camptothecin, and pharmaceutically-acceptable salts thereof; (ii) methods of synthesis of said novel germanium-containing camptothecin compound, 7[2′-trimethylgermanyl]ethyl-20(S) camptothecin, and pharmaceutically-acceptable salts; (iii) pharmaceutically-acceptable formulations comprising said novel germanium-containing camptothecin compound, 7[2′-trimethylgermanyl]ethyl-20(S) camptothecin, and pharmaceutically-acceptable salts thereof; and (iv) methods of administration of said novel germanium-containing camptothecin compound, 7[2′-trimethylgermanyl]ethyl-20(S) camptothecin, and pharmaceutically-acceptable salts thereof to subjects in need thereof, including subjects with cancer.
摘要翻译：本发明公开：（i）新颖的含锗喜树碱化合物，7 [2'-三甲基甲酰基]乙基-20（S）喜树碱及其药学上可接受的盐; （ii）合成所述新颖的含锗喜树碱化合物的方法，7 [2'-三甲基麦角糖基]乙基-20（S）喜树碱及其药学上可接受的盐; （iii）包含所述新颖的含锗喜树碱化合物，7 [2'-三甲基麦角糖基]乙基-20（S）喜树碱的药学上可接受的制剂及其药学上可接受的盐; 和（iv）将所述新颖的含锗喜树碱化合物，7 [2'-三甲基甲酰基]乙基-20（S）喜树碱及其药学上可接受的盐给予需要的受试者，包括患有癌症的受试者的方法。

76. 发明授权

US08143236B2 Chemoprotective methods 有权
标题翻译：化学保护方法
公开(公告)号：US08143236B2
公开(公告)日：2012-03-27
申请号：US12075898
申请日：2008-03-14
申请人： Frederick H. Hausheer
发明人： Frederick H. Hausheer
IPC分类号： A61K31/665 , A61K31/66 , A61K31/28
CPC分类号： A61K31/105
摘要： Compositions and methods for reducing, preventing, mitigating, and/or delaying the onset of, attenuating the severity of, and/or hastening the resolution of, for example, one or more chemotherapy-associated toxicities in a subject receiving one or more chemotherapeutic agents. In addition compositions and methods for mitigating or preventing a novel form of chemotherapy-induced peripheral neuropathy are disclosed and claimed.
摘要翻译：用于减少，预防，减轻和/或延缓接受一种或多种化学治疗剂的受试者中例如一种或多种化疗相关毒性的分解的减轻，和/或促进其分解的组合物和方法。此外，公开并要求保护减轻或预防化疗诱发的周围神经病变的新形式的组合物和方法。

77. 发明授权

US08026227B2 Chemoprotective methods and compositions 失效
标题翻译：化学保护方法和组合物
公开(公告)号：US08026227B2
公开(公告)日：2011-09-27
申请号：US11638193
申请日：2006-12-13
申请人： Frederick H. Hausheer
发明人： Frederick H. Hausheer
IPC分类号： A61K31/665 , A61K31/66 , A61K31/335 , A61K31/28
CPC分类号： A61K31/185 , A61K31/255
摘要： Compositions and methods for reducing, preventing, mitigating, and/or delaying the onset of, attenuating the severity of, and/or hastening the resolution of, for example, one or more chemotherapy-associated toxicities in a subject receiving one or more chemotherapeutic agents.
摘要翻译：用于减少，预防，减轻和/或延缓接受一种或多种化学治疗剂的受试者中例如一种或多种化疗相关毒性的分解的减轻，和/或促进其分解的组合物和方法。

78. 发明授权

US07268244B2 Monoimine ligand platinum analogs 有权
公开(公告)号：US07268244B2
公开(公告)日：2007-09-11
申请号：US11340806
申请日：2006-01-26
申请人： Frederick H. Hausheer , Zejun Xiao , Harry Kochat
发明人： Frederick H. Hausheer , Zejun Xiao , Harry Kochat
IPC分类号： C07F15/00 , A61K31/28
CPC分类号： C07F15/0093
摘要： Disclosed herein are novel platinum-based analogs with a single substituted imine ligand: R7RC═NR8, wherein the R7RC═NR8 functional group is covalently bonded to the platinum through nitrogen. The analogs also have nitrogen donor ligands capable of forming hydrogen bonds with the bases in DNA or RNA, and one or more leaving groups which can be displaced by water, hydroxide ions or other nucleophiles, which is thought to form active species in vivo, and then, form cross-linked complexes between nucleic acid strands, principally between purines in DNA (or RNA), i.e., at the Guanine or Adenine bases, thereof. These platinum analogs may also be more easily transported into tumor cells, due to their increased lipophilicity and are likely to be useful as anti-neoplastic agents, and in modulating or interfering with the synthesis or replication or transcription of DNA or translation or function of RNA in vitro or in vivo, as they are potentially capable of forming a platinum coordinate complex with a intact or nascent DNA or RNA and thereby interfering with cellular synthesis, transcription or replication of nucleic acid polynucleotides.

79. 发明授权

US07238823B2 Platinum complexes with mononitrile-containing ligands 失效
标题翻译：铂配合物与含有单腈的配体
公开(公告)号：US07238823B2
公开(公告)日：2007-07-03
申请号：US11340048
申请日：2006-01-26
申请人： Zejun Xiao , Frederick H. Hausheer , Pavankumar Petluru
发明人： Zejun Xiao , Frederick H. Hausheer , Pavankumar Petluru
IPC分类号： C07F15/00 , A61K31/28
CPC分类号： C07F15/0093
摘要： Disclosed herein are novel platinum-based complexes possessing one nitrile substituent group (mononitrile) covalently-bonded to the platinum, one or more nitrogen donor ligands capable of forming hydrogen bonds with the bases in DNA or RNA and leaving groups (i.e., L1 and L2) which can be hydrolyzed in vivo to active species, which can then form coordinate adducts with DNA or RNA at the Guanine or Adenine bases thereof. Also disclosed herein are the reaction schemes for the synthesis of said platinum complexes, as well as methods of treatment of various types of cancer by the administration of a pharmaceutically-effective dose of said novel platinum complexes.
摘要翻译：本文公开了具有与铂共价连接的一个腈取代基（单腈）的新型铂基络合物，能够与DNA或RNA中的碱形成氢键的离子基团（即L

80. 发明授权

US07235589B2 Method of treating patients undergoing kidney dialysis 有权
标题翻译：治疗肾透析患者的方法
公开(公告)号：US07235589B2
公开(公告)日：2007-06-26
申请号：US10945810
申请日：2004-09-21
申请人： Frederick H. Hausheer
发明人： Frederick H. Hausheer
IPC分类号： A61K31/10
CPC分类号： A61K31/185 , A61K31/66
摘要： This invention relates to a method of treating patients who are receiving dialysis treatments. The method includes administering to a patient in need of treatment an effective amount of a thiol or reducible disulfide compound according to the formula set forth in the specification.
摘要翻译：本发明涉及一种治疗正在接受透析治疗的患者的方法。该方法包括向需要治疗的患者施用有效量的根据说明书中阐述的式的硫醇或可还原的二硫化物化合物。

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