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1. 发明专利

CA2145207A1 METHODS FOR IDENTIFYING AND USING LOW/NON-ADDICTIVE OPIOID ANALGESICS 未知
公开(公告)号：CA2145207A1
公开(公告)日：1994-03-22
申请号：CA2145207
申请日：1993-09-17
申请人： QIN BO YI , GONG XIONG QI , CRAIN STANLEY M , MAO HUANG , YI WANG CHANG , SHEN KE FEI
发明人： QIN BO-YI , SHEN KE-FEI , GONG XIONG-QI , CRAIN STANLEY M , MAO HUANG , YI WANG CHANG
IPC分类号： G01N33/53 , A61K31/00 , A61K31/485 , C07D489/00 , G01N33/94 , C12Q1/02 , C07D489/12
摘要： The present invention relates to a method of using a bioassay consisting of an electrophysiological method and a cell culture system of dorsal-root ganglion (DRG) neurons to screen and identify opioids with a high potential for use as "low- or nonaddictive" analgesics. Another aspect of the invention relates to a specific group of opioid alkaloids and analogues thereof identified by the bioassay of the invention for the unique ability to activate only inhibitory, but not excitatory, opioid receptor function, for use as low- or non-addictive analgesics. Another aspect of the invention relates to the specific use of etorphine or dihydroetorphine of the opioid alkaloid family as low- or non-addictive analgesics and for the treatment of opioid addiction. The present invention also relates to the preparation of dihydroetorphine hydrochloride (7a-¢1-(R)-hydroxy-1-methylbutyl!-6,14-endo-ethano-tetrahydrooripavine hydrochloride) and a pharmaceutical composition comprising the compound as an active ingredient in the form of a pharmaceutically acceptable salt.

2. 发明公开

EP0668764A1 METHODS FOR IDENTIFYING AND USING LOW/NON-ADDICTIVE OPIOID ANALGESICS 失效
标题翻译：方法鉴定和使用阿片类镇痛药具有低或无依赖可能性。
公开(公告)号：EP0668764A1
公开(公告)日：1995-08-30
申请号：EP93921686.0
申请日：1993-09-17
申请人： QIN, Bo-yi , SHEN, Ke-fei , GONG, Xiong-qi , CRAIN, Stanley, M. , MAO, Huang , WANG, Chang, Yi
发明人： QIN, Bo-yi , SHEN, Ke-fei , GONG, Xiong-qi , CRAIN, Stanley, M. , MAO, Huang , WANG, Chang, Yi
IPC分类号： G01N33 , A61K31 , C07D489
CPC分类号： G01N33/9486 , A61K31/00 , A61K31/137 , A61K31/485 , G01N33/94 , G01N2500/10 , A61K2300/00
摘要： The present invention relates to a method of using a bioassay consisting of an electrophysiological method and a cell culture system of dorsal-root ganglion (DRG) neurons to screen and identify opioids with a high potential for use as 'low- or non-addictive' analgesics. Another aspect of the invention relates to a specific group of opioid alkaloids and analogues thereof identified by the bioassay of the invention for the unique ability to activate only inhibitory, but not excitatory, opioid receptor function, for use as low- or non-addictive analgesics. Another aspect of the invention relates to the specific use of etorphine or dihydroetorphine of the opioid alkaloid family as low- or non-addictive analgesics and for the treatment of opioid addiction. The present invention also relates to the preparation of dihydroetorphine hydrochloride (7α-[1-(R)-hydroxy-1-methylbutyl]-6,14-endo-ethano-tetrahydrooripavine hydrochloride) and a pharmaceutical composition comprising the compound as an active ingredient in the form of a pharmaceutically acceptable salt.

3. 发明申请

WO2008060381A3 METHOD FOR TREATING PAIN OR OPIOID DEPENDENCE USING A SPECIFIC TYPE OF NON-OPIOID AGENT IN COMBINATION WITH A SELECTIVE EXCITATORY-OPIOID-RECEPTOR INACTIVATOR 审中-公开
公开(公告)号：WO2008060381A3
公开(公告)日：2008-05-22
申请号：PCT/US2007/021836
申请日：2007-10-12
申请人： ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY , CRAIN, Stanley, M. , SHEN, Ke-Fei
发明人： CRAIN, Stanley, M. , SHEN, Ke-Fei
IPC分类号： A61K39/106 , A61K31/44 , A61K31/19 , A61K31/557 , A01N43/42 , A01N37/08 , A01N53/00
摘要： The present invention provides a method for treating pain in a subject in need of treatment, by administering to the subject a non-opioid agent in combination with a selective excitatory-opioid-receptor inactivator, in amounts effective to treat pain in the subject. Also disclosed is a method for treating opioid-withdrawal effects in a subject in need of treatment, by the administration to the subject of a non-opioid agent in combination with a selective excitatory-opioid-receptor inactivator, in amounts effective to treat opioid-withdrawal effects in the subject. Finally, the present invention provides a pharmaceutical composition comprising a non-opioid agent and a selective excitatory- opioid-receptor inactivator, and a pharmaceutically-acceptable carrier.

4. 发明申请

WO2008060381A2 METHOD FOR TREATING PAIN OR OPIOID DEPENDENCE USING A SPECIFIC TYPE OF NON-OPIOID AGENT IN COMBINATION WITH A SELECTIVE EXCITATORY-OPIOID-RECEPTOR INACTIVATOR 审中-公开
标题翻译：使用特定类型的非阿片类药物与选择性兴奋剂 - 阿片受体抑制剂组合治疗疼痛或阿片类药物依赖性的方法
公开(公告)号：WO2008060381A2
公开(公告)日：2008-05-22
申请号：PCT/US2007021836
申请日：2007-10-12
申请人： EINSTEIN COLL MED , CRAIN STANLEY M , SHEN KE-FEI
发明人： CRAIN STANLEY M , SHEN KE-FEI
IPC分类号： A61K31/198
CPC分类号： A61K31/198 , A61K31/4015 , A61K45/06 , A61K2300/00
摘要： The present invention provides a method for treating pain in a subject in need of treatment, by administering to the subject a non-opioid agent in combination with a selective excitatory-opioid-receptor inactivator, in amounts effective to treat pain in the subject. Also disclosed is a method for treating opioid-withdrawal effects in a subject in need of treatment, by the administration to the subject of a non-opioid agent in combination with a selective excitatory-opioid-receptor inactivator, in amounts effective to treat opioid-withdrawal effects in the subject. Finally, the present invention provides a pharmaceutical composition comprising a non-opioid agent and a selective excitatory- opioid-receptor inactivator, and a pharmaceutically-acceptable carrier.
摘要翻译：本发明提供治疗需要治疗的受试者的疼痛的方法，其通过以有效治疗受试者疼痛的量向受试者施用非阿片样物质与选择性兴奋性 - 阿片样物质受体失活剂的组合。还公开了一种治疗需要治疗的受试者的阿片样物质戒断作用的方法，通过向受治疗者施用有效治疗阿片样物质戒断作用的量的非阿片样物质与选择性兴奋性 - 阿片样物质受体失活剂，主题中的撤回效应。最后，本发明提供了包含非阿片样物质和选择性兴奋性阿片受体失活剂和药学上可接受的载体的药物组合物。

5. 发明申请

WO0067739A2 COMPOSITIONS AND METHODS FOR ENHANCING ANALGESIC POTENCY OF TRAMADOL AND ATTENUATING ITS ADVERSE SIDE EFFECTS 审中-公开
标题翻译：组合物和方法，用于增强TRAMADOL的有效磷酸化和不利影响其副作用
公开(公告)号：WO0067739A2
公开(公告)日：2000-11-16
申请号：PCT/US0012493
申请日：2000-05-05
申请人： PAIN THERAPEUTICS INC , EINSTEIN COLL MED , CRAIN STANLEY M , SHEN KE FEI , SHERMAN BARRY , REMIEN MARY , BARBIER REMI , FRIEDMANN NADAV
发明人： CRAIN STANLEY M , SHEN KE-FEI , SHERMAN BARRY , REMIEN MARY , BARBIER REMI , FRIEDMANN NADAV
IPC分类号： A61K45/00 , A61K31/00 , A61K31/137 , A61K31/485 , A61K38/33 , A61P25/04 , A61P43/00 , G01N33/94
CPC分类号： A61K31/485 , A61K31/00 , A61K38/33 , G01N33/94 , G01N33/9486 , G01N2500/10 , A61K31/135 , A61K2300/00
摘要： The invention generally relates to compositions and methods with tramadol and an opioid antagonist to enhance analgesic potency and/or attenuate one or more adverse effects of tramadol, including adverse side effect(s) in humans such as nausea, vomiting, dizziness, headache, sedation (somnolence) or pruritis. This invention relates to compositions and methods for selectively enhancing the analgesic potency of tramadol and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of tramadol. The methods of the present invention comprise administering to a subject an analgesic or subanalgesic amount of tramadol and an amount of excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of tramadol and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of tramadol.
摘要翻译：本发明一般涉及具有曲马多和阿片样物质拮抗剂以增强镇痛效力和/或减弱曲马多的一种或多种不良反应的组合物和方法，包括人类的不良副作用，例如恶心，呕吐，头晕，头痛，镇静（嗜睡）或瘙痒症。本发明涉及用于选择性增强曲马多镇痛效力的组合物和方法，同时减轻与施用曲马多相关的抗镇痛，痛觉过敏，过度兴奋，身体依赖和/或耐受性作用。本发明的方法包括对受试者施用止痛剂或亚麻痛剂量的曲马多和一定量的兴奋性阿片样物质受体拮抗剂如纳曲酮或纳美芬，其有效地增强曲马多的止痛效力并减弱镇痛，痛觉过敏，兴奋性过高，曲马多的身体依赖和/或耐受性影响。

6. 发明申请

WO1994006426A1 METHODS FOR IDENTIFYING AND USING LOW/NON-ADDICTIVE OPIOID ANALGESICS 审中-公开
标题翻译：识别和使用低/非阿片类药物的方法
公开(公告)号：WO1994006426A1
公开(公告)日：1994-03-31
申请号：PCT/US1993008869
申请日：1993-09-17
申请人： QIN, Bo-yi , SHEN, Ke-fei , GONG, Xiong-qi , CRAIN, Stanley, M. , MAO, Huang , WANG, Chang, Yi
IPC分类号： A61K31/46
CPC分类号： G01N33/9486 , A61K31/00 , A61K31/137 , A61K31/485 , G01N33/94 , G01N2500/10 , A61K2300/00
摘要： The present invention relates to a method of using a bioassay consisting of an electrophysiological method and a cell culture system of dorsal-root ganglion (DRG) neurons to screen and identify opioids with a high potential for use as "low- or non-addictive" analgesics. Another aspect of the invention relates to a specific group of opioid alkaloids and analogues thereof identified by the bioassay of the invention for the unique ability to activate only inhibitory, but not excitatory, opioid receptor function, for use as low- or non-addictive analgesics. Another aspect of the invention relates to the specific use of etorphine or dihydroetorphine of the opioid alkaloid family as low- or non-addictive analgesics and for the treatment of opioid addiction. The present invention also relates to the preparation of dihydroetorphine hydrochloride (7(alpha)-(1-(R)-hydroxy-1-methylbutyl)-6,14-endo-ethano-tetrahydrooripavine hydrochloride) and a pharmaceutical composition comprising the compound as an active ingredient in the form of a pharmaceutically acceptable salt.
摘要翻译：本发明涉及使用由电生理学方法和背根神经节（DRG）神经元的细胞培养系统组成的生物测定法来筛选和鉴定具有高潜力用作“低或非成瘾性”的阿片样物质的方法，镇痛药。本发明的另一方面涉及通过本发明的生物测定鉴定的特定组的阿片样物质生物碱及其类似物，其特征在于仅使用抑制性但不兴奋性的阿片受体功能仅用于作为低或非成瘾性止痛剂。本发明的另一方面涉及阿片样物质生物碱家族的吗啡或二氢阿托啡作为低或非成瘾止痛剂和用于治疗阿片样物质成瘾的具体用途。本发明还涉及二氢阿托啡盐酸盐（7（α） - （1-（R） - 羟基-1-甲基丁基）-6,14-内 - 乙酸 - 四氢奥帕匹酸盐酸盐的制备）和包含该化合物呈药学上可接受的盐形式的活性成分。

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