公开(公告)号：US20060128721A1

公开(公告)日：2006-06-15

申请号：US10560476

申请日：2004-06-07

申请人： Frans Janssens ,  Francois Sommen ,  Benoit Christian Albert Ghislain De Boeck ,  Joseph Elisabeth Leenaerts ,  Yves Emiel, Maria Van Roosbroeck ,  Theo Frans Meert

发明人： Frans Janssens ,  Francois Sommen ,  Benoit Christian Albert Ghislain De Boeck ,  Joseph Elisabeth Leenaerts ,  Yves Emiel, Maria Van Roosbroeck ,  Theo Frans Meert

IPC分类号： A61K31/496

CPC分类号： A61K45/06 ,  A61K31/496 ,  A61K31/551 ,  A61K2300/00

摘要： This invention concerns novel formulations for opioid-based treatments of pain and/or nociception comprising opioid analgesics and 1,4-di-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, the use of said formulation for the manufacture of a medicament for the prevention and/or treatment of emesis, pain and/or nociception, in particular in opioid-based acute and chronic pain treatments, more in particular in inflammatory, post-operative, emergency room (ER), breakthrough, neuropathic and cancer pain treatments and the use of an NK1-receptor antagonist for the manufacture of a medicament for the prevention and/or treatment of respiratory depression in opioid-based treatments of pain. The pharmaceutical formulations according to the invention comprise a pharmaceutically acceptable carrier and, as active ingredients, a therapeutically effective amount of an opioid analgesic and NK1-antagonists according to the general Formula (I) the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in claim 1. The pharmaceutical composition according to the invention reduces to a large extent a number of unwanted side-effects associated with opioid analgesics, in particular emesis, respiratory depression and tolerance, thereby increasing the total tolerability of said opioids in pain treatment.

摘要翻译： 本发明涉及用于基于阿片样物质治疗疼痛和/或伤害感受的新制剂，其包含具有神经激肽拮抗活性的阿片类镇痛药和1,4-二哌啶-4-基 - 哌嗪衍生物，特别是NK1 拮抗活性，所述制剂用于制备用于预防和/或治疗呕吐，疼痛和/或伤害感受，特别是基于阿片样物质的急性和慢性疼痛治疗的药物的用途，特别是在炎性， 手术，急诊室（ER），突破性，神经病理性和癌症疼痛治疗，以及使用NK 1受体拮抗剂制备用于预防和/或治疗阿片样物质中呼吸抑制的药物 的治疗疼痛。 根据本发明的药物制剂包含药学上可接受的载体，并且作为活性成分，具有治疗有效量的根据通式（I）的药学上可接受的酸的阿片样物质止痛剂和NK 1拮抗剂 或其碱加成盐，其立体化学异构形式，其N-氧化物形式和其前药，其中所有取代基如权利要求1中所定义。根据本发明的药物组合物在很大程度上降低了多个不需要的副产物， 与阿片类止痛药相关的作用，特别是呕吐，呼吸抑制和耐受性，从而增加所述阿片类药物在疼痛治疗中的总耐受性。

公开(公告)号：US08637510B2

公开(公告)日：2014-01-28

申请号：US13512464

申请日：2010-11-25

申请人： Gregor James Macdonald ,  Benoit Christian Albert Ghislain De Boeck ,  Joseph Elisabeth Leenaerts

发明人： Gregor James Macdonald ,  Benoit Christian Albert Ghislain De Boeck ,  Joseph Elisabeth Leenaerts

IPC分类号： A61K31/535 ,  C07D413/14

CPC分类号： C07D417/14

摘要： The present invention relates to morpholinothiazole derivatives and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to positive allosteric modulators of nicotinic acetylcholine receptors, such positive allosteric modulators having the capability to increase the efficacy of nicotinic receptor agonists.

摘要翻译： 本发明涉及吗啉代噻唑衍生物及其药学上可接受的盐，其制备方法，含有它们的药物组合物及其在治疗中的用途。 本发明特别涉及烟碱乙酰胆碱受体的正变构调节剂，这种正性变构调节剂具有增加烟碱受体激动剂功效的能力。