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1. 发明授权

US07438904B1 High-activity mutants of butyrylcholinesterase for cocaine hydrolysis and method of generating the same 有权
标题翻译：用于可卡因水解的丁酰胆碱酯酶的高活性突变体及其产生方法
公开(公告)号：US07438904B1
公开(公告)日：2008-10-21
申请号：US11243111
申请日：2005-10-04
申请人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
发明人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
IPC分类号： A61K38/46 , C12N9/16
CPC分类号： C12N9/18 , A61K38/00 , C12Y301/01008
摘要： A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (−)-cocaine compared with wild-type BChE.
摘要翻译：提供了一种新颖的计算方法和用于可卡因水解的突变丁酰胆碱酯酶的产生。该方法包括对可能的BChE突变体进行分子建模，并进行分子动力学模拟和混合量子力学/分子机械计算，从而通过预测哪个突变体将导致速率确定步骤的更稳定的过渡状态来提供可能的BChE突变体的筛选方法。对于可能的BChE突变体，即与野生型BChE相比预测具有更高催化效率的突变体，对计算确定的突变体进行定点诱变，蛋白质表达和蛋白质活性。此外，突变体A199S / A328W / Y332G，A199S / F227A / A328W / Y332G，A199S / S287G / A328W / Y332G，A199S / F227A / S287G / A328W / Y332G和A199S / F227A / S287G / A328W / E441D都具有增强的催化（ - ） - 可卡因与野生型BChE相比有效。

2. 发明授权

US07919082B1 High-activity mutants of butyrylcholinesterase for cocaine hydrolysis and method of generating the same 有权
标题翻译：用于可卡因水解的丁酰胆碱酯酶的高活性突变体及其产生方法
公开(公告)号：US07919082B1
公开(公告)日：2011-04-05
申请号：US12752920
申请日：2010-04-01
申请人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
发明人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
IPC分类号： A61K38/46 , C12N9/16
CPC分类号： C12N9/18 , A61K38/00 , C12Y301/01008
摘要： A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (−)-cocaine compared with wild-type BChE.
摘要翻译：提供了一种新颖的计算方法和用于可卡因水解的突变丁酰胆碱酯酶的产生。该方法包括对可能的BChE突变体进行分子建模，并进行分子动力学模拟和混合量子力学/分子机械计算，从而通过预测哪个突变体将导致速率确定步骤的更稳定的过渡状态来提供可能的BChE突变体的筛选方法。对于可能的BChE突变体，即与野生型BChE相比预测具有更高催化效率的突变体，对计算确定的突变体进行定点诱变，蛋白质表达和蛋白质活性。此外，突变体A199S / A328W / Y332G，A199S / F227A / A328W / Y332G，A199S / S287G / A328W / Y332G，A199S / F227A / S287G / A328W / Y332G和A199S / F227A / S287G / A328W / E441D都具有增强的催化（ - ） - 可卡因与野生型BChE相比有效。

3. 发明授权

US07731957B1 High-activity mutants of butyrylcholinesterase for cocaine hydrolysis and method of generating the same 有权
标题翻译：用于可卡因水解的丁酰胆碱酯酶的高活性突变体及其产生方法
公开(公告)号：US07731957B1
公开(公告)日：2010-06-08
申请号：US12192394
申请日：2008-08-15
申请人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
发明人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
IPC分类号： A61K38/46 , C12N9/16
CPC分类号： C12N9/18 , A61K38/00 , C12Y301/01008
摘要： A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (−)-cocaine compared with wild-type BChE.
摘要翻译：提供了一种新颖的计算方法和用于可卡因水解的突变丁酰胆碱酯酶的产生。该方法包括对可能的BChE突变体进行分子建模，并进行分子动力学模拟和混合量子力学/分子机械计算，从而通过预测哪个突变体将导致速率确定步骤的更稳定的过渡状态来提供可能的BChE突变体的筛选方法。对于可能的BChE突变体，即与野生型BChE相比预测具有更高催化效率的突变体，对计算确定的突变体进行定点诱变，蛋白质表达和蛋白质活性。此外，突变体A199S / A328W / Y332G，A199S / F227A / A328W / Y332G，A199S / S287G / A328W / Y332G，A199S / F227A / S287G / A328W / Y332G和A199S / F227A / S287G / A328W / E441D都具有增强的催化（ - ） - 可卡因与野生型BChE相比有效。

4. 发明授权

US08399644B1 High-activity mutants of butyrylcholinesterase for cocaine hydrolysis and method of generating the same 有权
公开(公告)号：US08399644B1
公开(公告)日：2013-03-19
申请号：US13449107
申请日：2012-04-17
申请人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
发明人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
IPC分类号： C07H21/04 , C12N9/18
CPC分类号： C12N9/18 , A61K38/00 , C12Y301/01008
摘要： A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (−)-cocaine compared with wild-type BChE.

5. 发明授权

US08193327B1 High-activity mutants of butyrylcholinesterase for cocaine hydrolysis and method of generating the same 有权
标题翻译：用于可卡因水解的丁酰胆碱酯酶的高活性突变体及其产生方法
公开(公告)号：US08193327B1
公开(公告)日：2012-06-05
申请号：US13018641
申请日：2011-02-01
申请人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
发明人： Chang-Guo Zhan , Hoon Cho , Hsin-Hsiung Tai
IPC分类号： C07H21/04 , C12N9/18
CPC分类号： C12N9/18 , A61K38/00 , C12Y301/01008
摘要： A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (−)-cocaine compared with wild-type BChE.
摘要翻译：提供了一种新颖的计算方法和用于可卡因水解的突变丁酰胆碱酯酶的产生。该方法包括对可能的BChE突变体进行分子建模，并进行分子动力学模拟和混合量子力学/分子机械计算，从而通过预测哪个突变体将导致速率确定步骤的更稳定的过渡状态来提供可能的BChE突变体的筛选方法。对于可能的BChE突变体，即与野生型BChE相比预测具有更高催化效率的突变体，对计算确定的突变体进行定点诱变，蛋白质表达和蛋白质活性。此外，突变体A199S / A328W / Y332G，A199S / F227A / A328W / Y332G，A199S / S287G / A328W / Y332G，A199S / F227A / S287G / A328W / Y332G和A199S / F227A / S287G / A328W / E441D都具有增强的催化（ - ） - 可卡因与野生型BChE相比有效。

6. 发明授权

US06743436B1 Anesthetic composition for intravenous injection comprising propofol 失效
标题翻译：用于静脉内注射的麻醉组合物包含异丙酚
公开(公告)号：US06743436B1
公开(公告)日：2004-06-01
申请号：US10018663
申请日：2001-12-21
申请人： Hyuk-Koo Lee , Ji-Young Jin , Hoon Cho
发明人： Hyuk-Koo Lee , Ji-Young Jin , Hoon Cho
IPC分类号： A61F202
CPC分类号： A61K9/1075 , A61K31/05
摘要： An anesthetic composition for intravenous injection, comprising propofol (2,6-diisopropylphenol) and Poloxamer POLOXAMER (Polyoxyethylene-polyoxypropylene copolymer) as surfactant is disclosed. The composition optionally can contain at least one co-surfactant selected from the group consisting of SOLUTOL HS 15 (Macrogol-15 Hydroxystearate), egg lecithin, LABRASOL (Polyoxy capryllic glyceride), polyoxy 10-oleyl-ether, TWEEN (polyoxyethylene sorbitan fatty acid esters), ethanol and polyethylene glycol. Because the composition is usually prepared in the form of an oil-in-water microemulsion having a particle size of 100 nm and below, it has superior technical effects in that it is thermodynamically stable and can be aseptically filtered to prevent microorganism contamination. Moreover, the composition is readily prepared so that side effects such as embolism, hyperlipidemia, etc. can be minimized.
摘要翻译：公开了一种用于静脉注射的麻醉组合物，其包含异丙酚（2,6-二异丙基苯酚）和泊洛沙姆POLOXAMER（聚氧乙烯 - 聚氧丙烯共聚物）作为表面活性剂。组合物任选地可以含有至少一种选自SOLUTOL HS 15（Macrogol-15羟基硬脂酸酯），卵磷脂，LABRASOL（聚氧丙烯酸甘油酯），聚氧十油基醚，TWEEN（聚氧乙烯脱水山梨糖醇脂肪酸酯），乙醇和聚乙二醇。由于该组合物通常以粒径为100nm以下的水包油微乳液的形式制备，所以具有优异的技术效果，因为其具有热力学稳定性，可无菌过滤以防止微生物污染。此外，容易制备组合物，使得可以使诸如栓塞，高脂血症等的副作用最小化。

7. 发明授权

US08637558B2 Thiazolidinedione derivative and use thereof 有权
标题翻译：噻唑烷二酮衍生物及其用途
公开(公告)号：US08637558B2
公开(公告)日：2014-01-28
申请号：US13142924
申请日：2009-12-30
申请人： Hoon Cho , Ying Wu , Cheol-Hee Choi
发明人： Hoon Cho , Ying Wu , Cheol-Hee Choi
IPC分类号： A61K31/426 , C07D277/34
CPC分类号： C07D277/34 , C07D277/36 , C07D413/12 , C07D417/12
摘要： The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.
摘要翻译：本发明涉及由下式（I）表示的新型噻唑烷二酮衍生物及其用途。更具体地，本发明涉及由下式（I）表示的新型噻唑烷二酮衍生物和包含其的药物组合物。根据本发明的式（I）的新型噻唑烷二酮衍生物可以通过抑制分解前列腺素的15-羟基前列腺素脱氢酶（15-PGDH）的活性而有效地用于预防或治疗心血管疾病，胃肠道疾病和肾脏疾病对于防止脱发和刺激毛发生长以及成骨刺激和伤口愈合有用。

8. 发明授权

US5922729A Water soluble polymer-tacrolimus conjugated compounds and process for preparing the same 失效
标题翻译：水溶性聚合物 - 他克莫司缀合的化合物及其制备方法
公开(公告)号：US5922729A
公开(公告)日：1999-07-13
申请号：US66818
申请日：1998-04-28
申请人： Pan Sup Chang , Hoon Cho
发明人： Pan Sup Chang , Hoon Cho
IPC分类号： C07D498/18 , A61K47/48 , C07D498/16 , A61K31/395 , A61K31/695 , C07F7/04
CPC分类号： C07D498/16 , A61K47/48215
摘要： The present invention relates to a tacrolimus conjugated compound represented by formula (I): ##STR1## in which R.sub.1 and R.sub.2 independently of one another represent hydrogen or a group of formula --CO--CH.sub.2 --X--(CH.sub.2 CH.sub.2 --O)n--CH.sub.3 wherein n denotes an integer of 10 to 460, andX represents O or S,provided that both R.sub.1 and R.sub.2 cannot be hydrogen;to a process for preparing the same and to its use as an immunosuppressive and antiinflammatory agent.
摘要翻译：本发明涉及由式（I）表示的他克莫司缀合的化合物：其中R 1和R 2彼此独立地表示氢或式-CO-CH 2 -X-（CH 2 CH 2 -O）n -CH 3的基团，其中n表示 10〜460的整数，X表示O或S，条件是R1和R2都不能为氢; 涉及其制备方法及其作为免疫抑制剂和抗炎剂的用途。

9. 发明申请

US20120137048A1 METHOD AND APPARATUS FOR IMPROVING ENDURANCE OF FLASH MEMORIES 有权
标题翻译：改善闪存记忆保护的方法和装置
公开(公告)号：US20120137048A1
公开(公告)日：2012-05-31
申请号：US12955765
申请日：2010-11-29
申请人： Hoon Cho , Kiran Pangal , Krishna K. Parat , Neal R. Mielke , Pranav Kalavade , Iwen Chao
发明人： Hoon Cho , Kiran Pangal , Krishna K. Parat , Neal R. Mielke , Pranav Kalavade , Iwen Chao
IPC分类号： G06F12/02 , G11C16/16 , G11C16/06 , G11C16/04
CPC分类号： G11C16/3495 , G11C16/02 , G11C16/3404
摘要： A method and apparatus for improving the endurance of flash memories. In one embodiment of the invention, a high electric field is provided to the control gate of a flash memory module. The high electric field applied to the flash memory module removes trapped charges between a control gate and an active area of the flash memory module. In one embodiment of the invention, the high electric field is applied to the control gate of the flash memory module prior to an erase operation of the flash memory module. By applying a high electric field to the control gate of the flash memory module, embodiments of the invention improve the Program/Erase cycling degradation of the single-level or multi-level cells of the flash memory module.
摘要翻译：一种提高闪存耐久性的方法和装置。在本发明的一个实施例中，高电场被提供给闪速存储器模块的控制门。施加到闪速存储器模块的高电场消除了控制栅极和闪存模块的有效区域之间的捕获的电荷。在本发明的一个实施例中，在闪速存储器模块的擦除操作之前，高电场被施加到闪速存储器模块的控制栅极。通过将高电场施加到闪速存储器模块的控制栅极，本发明的实施例改善了闪存模块的单级或多级单元的编程/擦除循环衰减。

10. 发明申请

US20110269954A1 NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF 有权
标题翻译：新型噻唑啉衍生物及其用途
公开(公告)号：US20110269954A1
公开(公告)日：2011-11-03
申请号：US13142924
申请日：2009-12-30
申请人： Hoon Cho , Ying Wu , Cheol-Hee Choi
发明人： Hoon Cho , Ying Wu , Cheol-Hee Choi
IPC分类号： C07D417/12 , C07D413/12 , C07D277/34
CPC分类号： C07D277/34 , C07D277/36 , C07D413/12 , C07D417/12
摘要： The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.
摘要翻译：本发明涉及由下式（I）表示的新型噻唑烷二酮衍生物及其用途。更具体地，本发明涉及由下式（I）表示的新型噻唑烷二酮衍生物和包含其的药物组合物。根据本发明的式（I）的新型噻唑烷二酮衍生物可以通过抑制分解前列腺素的15-羟基前列腺素脱氢酶（15-PGDH）的活性而有效地用于预防或治疗心血管疾病，胃肠道疾病和肾脏疾病对于防止脱发和刺激毛发生长以及成骨刺激和伤口愈合有用。

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