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1. 发明授权

US5508424A 4-arylisoindole analgesics 失效
标题翻译： 4-芳基异吲哚镇痛药
公开(公告)号：US5508424A
公开(公告)日：1996-04-16
申请号：US173586
申请日：1993-12-23
申请人： Richard J. Carmosin , John R. Carson , Dennis C. Liotta , Philip Pitis , Robert B. Raffa
发明人： Richard J. Carmosin , John R. Carson , Dennis C. Liotta , Philip Pitis , Robert B. Raffa
IPC分类号： C07D401/08 , A61K31/40 , A61K31/403 , A61K31/404 , A61K31/44 , A61K31/4427 , A61K31/4439 , A61P25/04 , C07D209/08 , C07D209/10 , C07D209/12 , C07D209/44 , C07D401/04 , C07D409/04 , C07D403/10 , A61K31/41 , C07D409/10
CPC分类号： C07D401/04 , C07D209/44
摘要： The 4-arylisoindoles of the following formula are effective analgesics: ##STR1## including stereoisomers and pharmaceutically acceptable salts thereof, wherein ##STR2## with the proviso that there is 0 or 1 unsaturated bond in the isoindole ring and with the proviso that where the stereoisomer is:a) the 3a.beta., 4.beta., 7a.alpha. diastereomer, then a double bond joins the 5- and 6-position carbons or the 6- and 7-position carbons;b) the 3a.beta., 4.alpha., 7a.alpha. or the 3a.beta., 4.alpha., 7a.beta. diastereomers, then the double bond joins the 5- and 6-position carbons; andc) the 3a.beta., 4.beta., 7a.beta. diastereomer, then the double bond joins the 6- and 7-position carbons.
摘要翻译：下式的4-芳基异吲哚是有效的镇痛药：其包括立体异构体及其药学上可接受的盐，其中“IMAGE”或“IMAGE”，条件是在异吲哚环中存在0或1个不饱和键，条件是立体异构体是：a）3aβ，4β，7aα非对映异构体，则双键连接5-和6-位碳原子或6-位和7-位碳; b）3aβ，4α，7aα或3aβ，4α，7aβ非对映异构体，则双键连接5-和6-位碳; 和c）3aβ，4β，7aβ非对映异构体，则双键连接6-和7-位碳。

2. 发明授权

US5543530A 4-arylisoindole analgesics 失效
标题翻译： 4-芳基异吲哚镇痛药
公开(公告)号：US5543530A
公开(公告)日：1996-08-06
申请号：US173326
申请日：1993-12-23
申请人： Richard J. Carmosin , John R. Carson , Philip Pitis , Robert B. Raffa
发明人： Richard J. Carmosin , John R. Carson , Philip Pitis , Robert B. Raffa
IPC分类号： A61K31/40 , A61K31/403 , A61K31/4035 , A61K31/404 , A61K31/4439 , A61P25/04 , C07D209/08 , C07D209/44 , C07D401/04 , C07D409/04 , A61K31/44
CPC分类号： C07D401/04 , C07D209/44 , C07D409/04
摘要： The 4-arylisoindoles of the following formula are effective analgesics: ##STR1## including the purified stereoisomers and pharmaceutically acceptable salts thereof,wherein ##STR2## R.sup.b is hydroxy or C.sub.1-5 alkylcarbonyloxy.
摘要翻译：下式的4-芳基异吲哚是有效的止痛剂：包括纯化的立体异构体及其药学上可接受的盐，其中R b是羟基或C 1-5烷基羰基氧基。

3. 发明授权

US5516803A Composition comprising a tramadol material and a non-steroidal anti-inflammatory drug 失效
标题翻译：组合物，其包含曲马多材料和非甾体抗炎药
公开(公告)号：US5516803A
公开(公告)日：1996-05-14
申请号：US397022
申请日：1995-03-01
申请人： Robert B. Raffa
发明人： Robert B. Raffa
IPC分类号： A61K31/19 , A61K31/405 , A61K31/415 , A61K31/42 , A61K31/60 , A61K31/135
CPC分类号： A61K31/415 , A61K31/19 , A61K31/405 , A61K31/42 , A61K31/60
摘要： This invention relates to a composition comprising a tramadol material and a nonsteroidal antiinflammatory drug, and its use. The compositions are pharmacologically useful in treating pain and tussive conditions. The compositions are also subject to less opioid side-effects such as abuse liability, tolerance, constipation and respiratory depression. Furthermore, where the components of the compositions are within certain ratios the pharmacological effects of the compositions are superadditive (synergistic).
摘要翻译：本发明涉及包含曲马多物质和非甾体抗炎药的组合物及其用途。组合物在药理学上可用于治疗疼痛和咳嗽状况。组合物也受到较少的阿片样物质副作用，例如滥用责任，耐受性，便秘和呼吸抑制。此外，当组合物的组分在一定比例内时，组合物的药理作用是超加性（协同）。

4. 发明授权

US5468744A Composition comprising a tramadol material and any of codeine, oxycodone or hydrocodone and their use 失效
标题翻译：组合物，其包含曲马多材料和任何可待因，羟考酮或氢可酮及其用途
公开(公告)号：US5468744A
公开(公告)日：1995-11-21
申请号：US268382
申请日：1994-06-30
申请人： Robert B. Raffa , Jeffrey L. Vaught
发明人： Robert B. Raffa , Jeffrey L. Vaught
IPC分类号： A61K31/135 , A61K31/485 , A61P1/12 , A61P11/14 , A61P19/00 , A61P25/04
CPC分类号： A61K31/485
摘要： This invention relates to compositions comprising a tramadol material selected from the group consisting of tramadol, its stereoisomers and its pharmaceutically acceptable salts and either codeine or oxycodone, and their use in treating pain. When the components, i.e., tramadol materials and either of codeine or oxycodone, of the composition are within certain ratios of pharmacological effects of the compositions are superaddditive (synergistic).
摘要翻译：本发明涉及包含选自曲马多，其立体异构体及其药学上可接受的盐和可待因或羟考酮的曲马多材料及其在治疗疼痛中的用途的组合物。当组合物，即组胺的曲马多物质和可待因或羟考酮中的任何一种在组合物的药理作用的一定比例内是超附加的（协同的）。

5. 发明授权

US5739139A Acetaminophen and dimenhydrinate analgesics 失效
标题翻译：对乙酰氨基酚和维生素酯镇痛药
公开(公告)号：US5739139A
公开(公告)日：1998-04-14
申请号：US667054
申请日：1996-06-20
申请人： Douglas R. Hough , Edward B. Nelson , Robert B. Raffa
发明人： Douglas R. Hough , Edward B. Nelson , Robert B. Raffa
IPC分类号： A61K31/52 , A61K31/165
CPC分类号： A61K31/52
摘要： Disclosed are compositions comprising acetaminophen (APAP) and dimenhydrinate and methods for their use in analgesia. When acetaminophen and dimenhydrinate are within certain ratios, their pharmacological effects are superadditive.
摘要翻译：公开了包含对乙酰氨基酚（APAP）和二甲苯胺酸盐的组合物及其用于止痛的方法。当对乙酰氨基酚和二甲苯磺酸盐在一定比例内时，其药理作用是超加性的。

6. 发明授权

US07662803B2 Method for treating warm-blooded vertebrates with halide-free glucosamine-acidic drug complexes 失效
标题翻译：用无卤素葡糖胺酸性药物复合物处理温血脊椎动物的方法
公开(公告)号：US07662803B2
公开(公告)日：2010-02-16
申请号：US11731600
申请日：2007-03-31
申请人： Alan Cowan , Robert B. Raffa , Ronald J. Tallarida
发明人： Alan Cowan , Robert B. Raffa , Ronald J. Tallarida
IPC分类号： A01N43/04 , A01N43/08 , C07H5/04 , C07H5/06 , C07H17/04
CPC分类号： A61K49/0008 , A61K31/726 , A61K45/06 , A61K2300/00
摘要： A method of treating a warm-blood vertebrate. The vertebrate may be a human being or a lower animal. The treatment method involves administering to the vertebrate in need of such treatment a pharmaceutically effective amount of a complex of halide-free glucosamine and a therapeutic drug having a pKa of less than 7. Preferably, the complex is stabilized by coating it with at least one pharmaceutically acceptable polymer comprising a water-soluble, water-immiscible and/or water-swellable homopolymer and/or copolymer. Suitable polymers include carboxypolymethylene homopolymers and copolymers; polyethylene glycol homopolymers and copolymers, povidone homopolymers and copolymers, polyacrylic acid homopolymers and copolymers; polyacrylamide homopolymers and copolymers; polysaccharides; and mixtures of two or more of the foregoing polymers. The resultant polymer-coated complex will be stable upon exposure to ambient temperature and/or the atmosphere. Suitable acidic therapeutic drugs may be found in one or more of the following classes of therapeutic drugs: α- and β-Adrenergic Agonists; Narcotic and Non-Narcotic Analgesics; Anorexics; Antiallergics; Antianginals; Antiarrhythmics; Antiasthmatics; Antibiotics; Anti-coagulants; Anticonvulsants; Antidepressants; Antidiabetics; Antihistaminics; Anti-hypertensives; Nonsteroidal Anti-Inflammatories; Antimigraines; Antineoplastics; Antiparkinsonians; Antipsychotics; Antipyretics; Antispasmodics; Antithrombotics; Anti-ulceratives; Anxiolytics; Decongestants; Diuretics; Hepatoprotectants; Sedatives; and Vasodilators.
摘要翻译：一种治疗温血脊椎动物的方法。脊椎动物可以是人或动物。治疗方法包括向需要这种治疗的脊椎动物施用药学有效量的无卤素葡糖胺和pKa小于7的治疗药物的复合物。优选地，复合物通过用至少一种包含水溶性，水不混溶和/或水可溶胀的均聚物和/或共聚物的药学上可接受的聚合物。合适的聚合物包括羧基聚亚甲基均聚物和共聚物; 聚乙二醇均聚物和共聚物，聚维酮均聚物和共聚物，聚丙烯酸均聚物和共聚物; 聚丙烯酰胺均聚物和共聚物; 多糖; 以及两种或更多种上述聚合物的混合物。所得聚合物涂覆的复合物在暴露于环境温度和/或气氛下将是稳定的。合适的酸性治疗药物可以在以下一类或多种治疗药物中发现：α-和β-肾上腺素能激动剂; 麻醉和非麻醉止痛药; 厌食症抗过敏药; Antianginals; 抗心律失常药抗哮喘药抗生素; 抗凝剂; 抗惊厥药; 抗抑郁药抗糖尿病患者抗组胺药抗高血压药; 非甾体抗炎药; 反义词抗肿瘤药物抗帕金森病抗精神病药解热药解痉药抗血栓药抗溃疡; 抗焦虑药减充血剂利尿剂; 肝保护剂; 镇静剂和血管扩张剂。

7. 再颁专利

USRE39221E1 Composition comprising a tramadol material and acetaminophen and its use 有权
标题翻译：包含曲马多材料和对乙酰氨基酚的组合物及其用途
公开(公告)号：USRE39221E1
公开(公告)日：2006-08-01
申请号：US10761096
申请日：2004-01-20
申请人： Robert B. Raffa , Jeffrey L. Vaught
发明人： Robert B. Raffa , Jeffrey L. Vaught
IPC分类号： A61K31/16
摘要： This invention relates to a composition comprising a tramadol material and acetaminophen, and its use. As used herein tramadol refers to various forms of tramadol. The compositions are pharmacologically useful in treating pain and tussive conditions. The compositions are also subject to less opioid side-effects such as abuse liability, tolerance, constipation and respiratory depression. Furthermore, where the components of the compositions are within certain ratios the pharmacological effects of the compositions are superadditive (synergistic).
摘要翻译：本发明涉及包含曲马多材料和对乙酰氨基酚的组合物及其用途。本文所用的曲马多是指各种形式的曲马多。组合物在药理学上可用于治疗疼痛和咳嗽状况。组合物也受到较少的阿片样物质副作用，例如滥用责任，耐受性，便秘和呼吸抑制。此外，当组合物的组分在一定比例内时，组合物的药理作用是超加性（协同）。

8. 发明授权

US5336691A Composition comprising a tramadol material and acetaminophen and its use 失效
标题翻译：包含曲马多材料和对乙酰氨基酚的组合物及其用途
公开(公告)号：US5336691A
公开(公告)日：1994-08-09
申请号：US974865
申请日：1992-11-10
申请人： Robert B. Raffa , Jeffrey L. Vaught
发明人： Robert B. Raffa , Jeffrey L. Vaught
IPC分类号： A61K31/135 , A61K31/165 , A61K31/166 , A61K31/167 , A61P25/04 , A61P29/00
CPC分类号： A61K31/165
摘要： This invention relates to a composition comprising a tramadol material and acetaminophen, and its use. As used herein tramadol refers to various forms of tramadol. The compositions are pharmacologically useful in treating pain and tussive conditions. The compositions are also subject to less opioid side-effects such as abuse liability, tolerance, constipation and respiratory depression. Furthermore, where the components of the compositions are within certain ratios the pharmacological effects of the compositions are superadditive (synergistic).
摘要翻译：本发明涉及包含曲马多材料和对乙酰氨基酚的组合物及其用途。本文所用的曲马多是指各种形式的曲马多。组合物在药理学上可用于治疗疼痛和咳嗽状况。组合物也受到较少的阿片样物质副作用，例如滥用责任，耐受性，便秘和呼吸抑制。此外，当组合物的组分在一定比例内时，组合物的药理作用是超加性（协同）。

9. 发明授权

US5223541A Tramadol N-oxide material, enantiomers and compositions thereof, and their use 失效
标题翻译： TRAMADOL氧化物材料，其成分及其组合物及其使用
公开(公告)号：US5223541A
公开(公告)日：1993-06-29
申请号：US759259
申请日：1991-09-13
申请人： Cynthia A. Maryanoff , Robert B. Raffa , Frank J. Villani
发明人： Cynthia A. Maryanoff , Robert B. Raffa , Frank J. Villani
IPC分类号： A61K31/14 , A61K31/135 , A61P1/12 , A61P11/14 , A61P25/04 , C07C291/04
CPC分类号： C07C291/04 , C07C2101/14 , Y10S514/85 , Y10S514/867
摘要： This invention relates to a tramadol N-oxide material, enantiomers and compositions thereof and their use. The tramadol N-oxide material and compositions thereof are pharmacologically useful in treating pain, diarrhea and tussive conditions. The tramadol N-oxide is also subject to less side-effects as compared to pure opiate based compositions, such as abuse liability, tolerance, constipation and respiratory depression. Furthermore, the tramadol N-oxide material when administered orally exhibits analgesia for a longer duration than an equi-analgesic amount of tramadol.

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