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1. 发明授权

US5026897A Carbaphens: aprophen analogs that are binary antidotes for organophosphate poisoning 失效
标题翻译： Carbaphens：aprophen类似物是有机磷酸盐中毒的二元解毒剂
公开(公告)号：US5026897A
公开(公告)日：1991-06-25
申请号：US580223
申请日：1990-09-10
申请人： Peter K. Chiang , Haim Leader , Ruthann M. Smejkal , Richard K. Gordon , Charlotte S. Payne , Bhupendra P. Doctor , Felipe N. Padilla
发明人： Peter K. Chiang , Haim Leader , Ruthann M. Smejkal , Richard K. Gordon , Charlotte S. Payne , Bhupendra P. Doctor , Felipe N. Padilla
IPC分类号： C07C219/10 , C07C271/44
CPC分类号： C07C271/44 , C07C219/10
摘要： Novel carbaphens are provided of the formula ##STR1## wherein R is OH, OCON(CH.sub.3).sub.2 or OCONHCH.sub.3, and R' is H, OH orsub.2 OCON(CH.sub.3).sub.2, stereoisomers thereof, pharmaceutically-acceptable salts thereof or mixtures thereof.Compositions comprise the carbaphens with pharmaceutically acceptable carriers, and they may further comprise other drugs as well.Methods of treating patients either prophylactically or therapeutically which suffer from organophosphate poisoning, coronary insufficiency, cerebral vasospasms, spastic cholitis and cholecystitis comprise the administration of the carbaphens of the invention.
摘要翻译：提供了新颖的碳酸酯，其中R为OH，OCON（CH 3）2或OCONHCH 3，R'为H，OH或2OCON（CH 3）2），其立体异构体，其药学上可接受的盐或其混合物。组合物包含具有药学上可接受的载体的碳青霉烯，并且它们还可以包含其它药物。治疗患有有机磷中毒，冠状动脉功能不全，脑血管痉挛，痉挛性胆囊炎和胆囊炎的患者的方法包括施用本发明的碳青霉烯。

2. 发明授权

US4973734A Carbaphens: aprophen analogs that are binary antidotes for organophosphate poisoning 失效
标题翻译： Carbaphens：aprophen类似物是有机磷酸盐中毒的二元解毒剂
公开(公告)号：US4973734A
公开(公告)日：1990-11-27
申请号：US325806
申请日：1989-03-17
申请人： Peter K. Chiang , Haim Leader , Ruthann M. Smeikal , Richard K. Gordon , Charlotte S. Payne , Bhupendra P. Doctor , Felipe N. Padilla
发明人： Peter K. Chiang , Haim Leader , Ruthann M. Smeikal , Richard K. Gordon , Charlotte S. Payne , Bhupendra P. Doctor , Felipe N. Padilla
IPC分类号： C07C219/10 , C07C271/44
CPC分类号： C07C271/44 , C07C219/10
摘要： Novel carbaphens are provided of the formula ##STR1## wherein R is OH, OCON(CH.sub.3).sub.2 or OCONHCH.sub.3, and R' is H, OH or .sub.2 OCON(CH.sub.3).sub.2, stereoisomers thereof, pharmaceutically-acceptable salts thereof or mixtures thereof.Compositions comprise the carbaphens with pharmaceutically acceptable carriers, and they may further comprise other drugs as well.Methods of treating patients either prophylactically or therapeutically which suffer from organophosphate poisoning, coronary insufficiency, cerebral vasospasms, spastic cholitis and cholecystitis comprise the administration of the carbaphens of the invention.
摘要翻译：提供了新颖的碳酸酯，其中R为OH，OCON（CH 3）2或OCONHCH 3，R'为H，OH或2OCON（CH 3）2），其立体异构体，其药学上可接受的盐或其混合物。组合物包含具有药学上可接受的载体的碳青霉烯，并且它们还可以包含其它药物。治疗患有有机磷中毒，冠状动脉功能不全，脑血管痉挛，痉挛性胆囊炎和胆囊炎的患者的方法包括施用本发明的碳青霉烯。

3. 发明授权

US07235521B1 Previns as specific inhibitors and therapeutic agents for botulinum toxin B and tetanus neurotoxins 失效
标题翻译：前列腺素作为肉毒杆菌毒素B和破伤风神经毒素的特异性抑制剂和治疗剂
公开(公告)号：US07235521B1
公开(公告)日：2007-06-26
申请号：US09979101
申请日：2000-05-15
申请人： Richard K. Gordon , Deborah R. Moorad , Bhupendra P. Doctor , Gregory E. Garcia
发明人： Richard K. Gordon , Deborah R. Moorad , Bhupendra P. Doctor , Gregory E. Garcia
IPC分类号： A61K38/00
CPC分类号： C12Q1/37 , G01N2333/95 , G01N2500/00
摘要： The compounds of the invention are generally described by the formula (1): B1Z*2B3Z*4X*5Q6F7X8X9X10X11, (2): B1X2X3X4X5Q6F7X8X9X10X11, or (3): B1X2B3X4Z5Q6F7Z8X9X10X11 and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.
摘要翻译：本发明的化合物通常由式（1）描述：B 1 Z * 2 B 3 Z * 4 < 5×6×6×6××××××××××××××××××××××××××××××××××××××××××< （2）：B 1 X 2 X 3 X 2 X 2 X 3 5 5 5 或（3）：B 1 X 2 B 3 3 5 X 5 5 5 它们的盐，酯，酰胺和酰基形式。由字母表示的每个位置表示单个氨基酸残基：B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。如下所述，氨基酸残基之间的一个或多个肽键可以被肽键模拟物代替。这些化合物可用作分子结构单元以产生针对抑制肉毒杆菌B和破伤风毒素的蛋白酶活性而优化的化合物。

4. 发明授权

US07375079B2 Previns as specific inhibitors and therapeutic agents for botulinum toxin B and tetanus neurotoxins 失效
公开(公告)号：US07375079B2
公开(公告)日：2008-05-20
申请号：US11268757
申请日：2005-11-04
申请人： Richard K. Gordon , Deborah R. Moorad , Bhupendra P. Doctor , Gregory E. Garcia
发明人： Richard K. Gordon , Deborah R. Moorad , Bhupendra P. Doctor , Gregory E. Garcia
IPC分类号： A61K38/00
CPC分类号： C07K7/06 , A61K38/00 , C07K7/08 , C07K7/22 , C07K14/8146
摘要： The compounds of the invention are generally described by the formula: B1Z*2B3Z*4X*5Q6F7X8X9X10X11, (1) B1X2X3X4X5Q6F7X8X9X10X11, or (2) B1Z2B3X4Z5Q6F7Z8X9X10X11 (3) and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic of polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large of hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum b and tetanus toxins.

5. 发明授权

US06573244B1 Previns as specific inhibitors and therapeutic agents for Botulinum toxin B and Tetanus neurotoxins 失效
标题翻译：前列腺素作为肉毒杆菌毒素B和破伤丹神经毒素的特异性抑制剂和治疗剂
公开(公告)号：US06573244B1
公开(公告)日：2003-06-03
申请号：US09570022
申请日：2000-05-12
申请人： Richard K. Gordon , Debbie R. Moorad , Bhupendra P. Doctor , Gregory E. Garcia
发明人： Richard K. Gordon , Debbie R. Moorad , Bhupendra P. Doctor , Gregory E. Garcia
IPC分类号： A61K3800
CPC分类号： C07K7/06 , A61K38/00 , C07K7/08 , C07K7/22 , C07K14/8146
摘要： The compounds of the invention are generally described by the formula: B1Z*2B3Z*4X*5Q6F7X8X9X10X11 (1), B1X2X3X4X5Q6F7X8X9X10X11 (2), or B1X2B3X4Z5Q6F7Z*8X9X10X11 (3) and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.
摘要翻译：本发明的化合物通常用下式描述：或其盐，酯，酰胺及其酰基形式。由字母表示的每个位置表示单个氨基酸残基：B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。如下所述，氨基酸残基之间的一个或多个肽键可以被肽键模拟物代替。这些化合物可以用作分子结构单元以产生针对抑制肉毒杆菌B和破伤风的蛋白酶活性而优化的化合物毒素

6. 发明授权

US06746850B2 Assay for detecting, measuring and monitoring the activities and concentrations of proteins and methods of use thereof 失效
公开(公告)号：US06746850B2
公开(公告)日：2004-06-08
申请号：US09848370
申请日：2001-05-04
申请人： Shawn R. Feaster , Richard K. Gordon , Bhupendra P. Doctor
发明人： Shawn R. Feaster , Richard K. Gordon , Bhupendra P. Doctor
IPC分类号： C12Q146
CPC分类号： C12Q1/005 , C12Q1/46 , G01N33/557 , G01N33/567
摘要： An assay for detecting, measuring, or monitoring the activity or concentration of at least two proteins that have similar or overlapping properties is disclosed. The assay comprises first determining the sensitivity coefficients of the substrates for each of the proteins in which the concentrations are to be determined. This method may be used for detecting, measuring, or monitoring the activity and concentration of AChE, BChE, or both in a test sample which test sample may be whole and unprocessed blood or tissue. Also disclosed are methods of using the assay to detect a subject's exposure to an agent which affects cholinesterase, determine the efficacy or progress of a treatment, determine the amount of protection provided against exposure to an agent which affects cholinesterase, or both, screen a subject for having a drug sensitivity or a particular disease, detect a change in red blood cell count of a subject, determine whether a candidate compound affects cholinesterase. Also disclosed are devices and kits for detecting, measuring, or monitoring the activities and concentrations of AChE, BChE, or both.

7. 发明授权

US06713444B1 Buforin I as a specific inhibitor and therapeutic agent for botulinum toxin B and tetanus neurotoxins 失效
标题翻译： Buforin I作为特异性抑制剂和肉毒杆菌毒素B和破伤风神经毒素的治疗剂
公开(公告)号：US06713444B1
公开(公告)日：2004-03-30
申请号：US09570023
申请日：2000-05-12
申请人： Gregory E. Garcia , Richard K. Gordon , Debbie R. Moorad , Bhupendra P. Doctor
发明人： Gregory E. Garcia , Richard K. Gordon , Debbie R. Moorad , Bhupendra P. Doctor
IPC分类号： A61K3800
CPC分类号： C07K14/8146 , A61K38/00
摘要： The compounds of the invention are generally described by the formula: X1X2B3X4B5X*6X7X8 B9X10B11X12B13X14 B15X16B17X*18X*19B20 X21X22X23Q24F25Z*26X27 X28B29X30B31B32X33X34 B35B36X37Z38Z39 (1) and the salts, esters, amides, and acyl forms thereof. Up to 15 amino acids may be truncated from the N-terminus and up to 6 amino acids may be truncated from the C-terminus. Each position represented by a letter indicates a single amino acid residue wherein B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. These compounds may be used to inhibit the protease activity of Botulinum B and tetanus toxins.
摘要翻译：本发明的化合物通常用下式描述：及其盐，酯，酰胺及其酰基形式。可以从N末端截断至多15个氨基酸，并且可以从C末端截断至多6个氨基酸。由字母表示的每个位置表示单个氨基酸残基，其中B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。这些化合物可用于抑制肉毒杆菌B和破伤风毒素的蛋白酶活性。

8. 发明授权

US06642037B2 Preparation of enzymatically active sponges or foams for detoxification of hazardous compounds 失效
标题翻译：制备用于有毒化合物解毒的酶活性海绵或泡沫
公开(公告)号：US06642037B2
公开(公告)日：2003-11-04
申请号：US09558512
申请日：2000-04-26
申请人： Richard K. Gordon , Bhupendra P. Doctor , Ashima Saxena , Shawn R. Feaster , Donald Maxwell , Michelle Ross , David Lenz , Keith Lejeune , Alan Russell
发明人： Richard K. Gordon , Bhupendra P. Doctor , Ashima Saxena , Shawn R. Feaster , Donald Maxwell , Michelle Ross , David Lenz , Keith Lejeune , Alan Russell
IPC分类号： C12N1104
CPC分类号： A62D3/00 , A61L2/16 , A61L2/235 , A62D3/02 , A62D2101/02 , A62D2101/26 , A62D2101/28 , C08G18/10 , C08G2101/0083 , C12N11/04 , C12N11/18 , C08G18/3821
摘要： An enzymatically active reusable sponge or foam, capable of regeneration with oximes, made of a polymer such as polyurethane is prepared for detoxification of hazardous compounds such as organophosphorus and organosulfur compounds. The foam or sponge contains a plurality of enzymes including enzymes selected from acetylcholinesterase, butyrylcholinesterase, triesterase, pseudocholinesterase, organophosphate hydrase, phosphotriesterase, paraoxonase and organophosphorus and organosulfur hydrolyzing enzymes. The sponge or foam may additionally contain activated carbon and an enzyme reactivation compound. A kit can be formed containing the sponge or foam and the compound for enzyme reactivation. The enzymatically active foam or sponge may be prepared using a two chamber device where enzymes and prepolymer are passed from separate chambers into a static mixing stator and are subjected to low shear mixing and extrusion to form by the sponge or foam.
摘要翻译：制备能够由诸如聚氨酯的聚合物制成的能够用肟再生的酶活性可重复使用的海绵或泡沫，用于有机磷和有机硫化合物等有害化合物的解毒。泡沫或海绵含有多种酶，包括选自乙酰胆碱酯酶，丁酰胆碱酯酶，三酯酶，假胆碱酯酶，有机磷酸盐水解酶，磷酸三酯酶，对氧磷酶和有机磷和有机硫水解酶的酶。海绵或泡沫可另外含有活性炭和酶再活化化合物。可以形成包含海绵或泡沫的试剂盒和用于酶再活化的化合物。酶活性泡沫或海绵可以使用两室装置制备，其中酶和预聚物从分离的室进入静态混合定子，并经受低剪切混合和挤出以由海绵或泡沫形成。

9. 发明授权

US06406876B1 Immobilized enzymes biosensors for chemical toxins 有权
标题翻译：固定化酶作为化学毒素的生物传感器
公开(公告)号：US06406876B1
公开(公告)日：2002-06-18
申请号：US09558511
申请日：2000-04-26
申请人： Richard K. Gordon , Bhupendra P. Doctor , Ashima Saxena , Shawn R. Feaster , Donald Maxwell , Michelle Ross , David Lenz , Keith LeJeune , Alan Russell
发明人： Richard K. Gordon , Bhupendra P. Doctor , Ashima Saxena , Shawn R. Feaster , Donald Maxwell , Michelle Ross , David Lenz , Keith LeJeune , Alan Russell
IPC分类号： C12Q146
CPC分类号： C12Q1/34 , C12Q1/26 , C12Q1/28 , C12Q1/42 , C12Q1/44 , C12Q1/46 , Y10S435/963 , Y10S435/97
摘要： Methods, compositions and materials useful in the detection of organophosphorous and organosulfur compounds are disclosed. In particular, biosensors wherein a porous or a non-porous support having an enzyme immobilized upon or within are disclosed. The biosensors exhibit enzymatic stability at extreme temperatures and/or denaturing conditions, and similar kinetic characteristics of the soluble form of the enzymes utilized. The enzyme does not leach from the porous or non-porous support and the material retains enzymatic activity after prolonged storage. Differential biosensors are also disclosed.
摘要翻译：公开了用于检测有机磷和有机硫化合物的方法，组合物和材料。特别地，公开了其中固定有或内部固定有酶的多孔或无孔载体的生物传感器。生物传感器在极端温度和/或变性条件下表现出酶稳定性，以及所用酶的可溶形式的类似动力学特征。该酶不会从多孔或非多孔载体中浸出，并且材料在长时间储存后保留酶活性。还公开了差示生物传感器。

10. 发明申请

US20110230473A1 Methods and Compositions for Treating Status Epilepticus and Seizures Causing Status Epilepticus 审中-公开
标题翻译：治疗癫痫持续状态和癫痫发作的方法和组成
公开(公告)号：US20110230473A1
公开(公告)日：2011-09-22
申请号：US13122901
申请日：2009-10-09
申请人： Richard K. Gordon , Madhusoodana P. Nambiar , James C. Demar , Ruthie H. Ratcliffe , Bhupendra P. Doctor , Roberta R. Owens
发明人： Richard K. Gordon , Madhusoodana P. Nambiar , James C. Demar , Ruthie H. Ratcliffe , Bhupendra P. Doctor , Roberta R. Owens
IPC分类号： A61K31/5513 , A61K31/439 , A61K31/44 , A61P25/08
CPC分类号： A61K31/435 , A61K31/44 , A61K31/4748 , A61K2300/00
摘要： Disclosed herein are methods, kits and compositions for treating, preventing, inhibiting, or reducing a seizure, status epilepticus, neuropathogenesis or a neuropathology caused by overstimulation of the NMDA receptor pathway and/or exposure to an OP compound.
摘要翻译：本文公开了用于治疗，预防，抑制或减少由过度刺激NMDA受体途径和/或暴露于OP化合物引起的癫痫持续状态，神经病变发生或神经病理学的方法，试剂盒和组合物。

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