Opiates are most commonly used as analgesics for treating severe chronic and acute pain. The opiate most frequently used at present for treating severe chronic or acute pain is morphine. An example of chronic pain is the pain which occurs in cancer. An example of acute pain is the pain which may occur after operations. The opiates used up until now for treating such pain are indeed highly effective but have a number of unpleasant and/or undesirable side effects, e.g. a short duration of activity, respiratory depression, nausea, constipation, diuresis and euphoria and they are also addictive.
Morphine hydrazone derivatives with analgesic activity are known from EP-A-0 242 417. EP-A-0 577 847 discloses 6-N-substituted morphine derivatives with analgesic and diuretic activity. EP-A-0 632 041 discloses 6-nicotinoylaminomorphine derivatives having analgesic activity.
A number of publications disclose preparations which attempt to avoid some of the known disadvantages of the opiates used up until now. EP-B-300 806 discloses the use of phospholipid vesicles for encapsulating opioid analgesics. EP-A-672 416, EP-A-647 448, EP-A-631 781 and WO 94/22431 disclose long-acting formulations of opiates in a hydrophobic matrix. All the formulations mentioned above have a duration of activity of from 12 to 24 hours. The disadvantages of these preparations are the delayed start of activity and the side effects, which still occur.