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A slow-release opioids drug system for postoperative pain relief

用于缓解术后疼痛的缓释阿片类药物系统

基本信息

批准号：
12557129
负责人：
DOHI Shuji
金额：
$ 6.46万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

It would be very convenient and practical that a slow release of opioid injected into the epidural space is able to be effective for 3〜4 days in postoperative patients. A copolymer paste containing opioid is such one possibility to provide more effective and convenient mean for postoperative analgesia.To examine such possibility as well as safety of epidural administration of an old opioid, oxycodone which, with oral slow releasing tablet, has recently been used in the US, we have done rats' experiments and found that oxycodone administered into the pontine reticular formation did not cause any sedative and analgesic effect, but its spinal administration caused a potent analgesia. Charbacol, a muscarinic agonist, produced analgesic action when administered both into the pontine and into the spinal subarachnoid space. Since morphine affects phosphorylation of MAPK kinase, we examined such effects of oxycodone using PC12 cell line and found that oxycodone did not affect activation of MAPK kinase. Then we have done clinical studies to examine effect of epidural oxycodone in 60 postoperative patients after approving with the human investigation committee. We found that epidural oxycodone is similarly effective for postoperative pain with less side effects such as nausea and vomiting.Although we could not be able to make a slow releasing solution of opioid which is available for epidural administration, it would provide a prolong analgesia for 3-4 days even with a single injection of such slow release of opioid into the epidural space. Since a drug company has recently started to make such injectable opioid with slow releasing property, research for a new drug-delivery system for injectable opioid would be promising.

术后患者硬膜外注射阿片类药物缓释3~4天是非常方便和实用的。一种含有阿片类药物的共聚物糊剂是一种为术后镇痛提供更有效和更方便手段的可能性。为了研究硬膜外给药的可能性和安全性，我们做了大鼠实验，发现在脑桥网状结构内给药的羟考酮没有任何镇静和镇痛作用，但它的脊髓给药有很强的镇痛作用。Charbacol是一种毒鼠碱激动剂，在脑桥和脊髓蛛网膜下腔给药时都有止痛作用。由于吗啡影响MAPK的磷酸化，我们用PC12细胞株检测了羟考酮的这种作用，发现羟考酮不影响MAPK的激活。并对60例术后患者经人类调查委员会批准后，进行了硬膜外羟考酮的临床研究。我们发现硬膜外羟考酮对术后疼痛同样有效，副作用较少，如恶心和呕吐。虽然我们不能制成可用于硬膜外给药的阿片缓释液，但即使将这种阿片缓释药物一次注入硬膜外间隙，它也可以提供3-4天的延长镇痛。由于一家制药公司最近开始制造这种具有缓释特性的可注射阿片类药物，因此研究一种新的可注射阿片类药物给药系统将是很有前途的。