A slow-release opioids drug system for postoperative pain relief

术后患者经硬膜外腔注入阿片类药物缓释，3 ~ 4天有效，是非常方便实用的。含有阿片类药物的共聚物膏体是提供更有效和方便的术后镇痛手段的一种可能性。为了检验硬膜外给药的可能性和安全性，最近在美国使用了一种古老的阿片类药物羟考酮，羟考酮与口服缓释片一起使用，我们做了大鼠实验，发现羟考酮给药到脑桥网状结构中没有任何镇静和镇痛作用，但脊髓给药可产生有效的镇痛作用。Charbacol是一种毒蕈碱激动剂，当同时注入脑桥和脊髓蛛网膜下腔时产生镇痛作用。由于吗啡影响MAPK激酶的磷酸化，我们使用PC12细胞系检测了羟考酮的这种作用，发现羟考酮不影响MAPK激酶的激活。经人体调查委员会批准，我们对60例术后患者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，副作用更少，如恶心和呕吐。虽然目前我们还不能研制出用于硬膜外给药的阿片类药物缓释溶液，但即使将这种缓释阿片类药物单次注入硬膜外腔，也能提供3-4天的长效镇痛。由于最近有制药公司开始生产这种具有缓释特性的注射用阿片类药物，因此研究一种新的注射用阿片类药物给药系统将是很有前途的。

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.