COVIDIEN Surgical Solutions, Bedford, MA, USA.
Reg Anesth Pain Med. 2012 Nov-Dec;37(6):607-15. doi: 10.1097/AAP.0b013e3182680f35.
To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed.
Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls.
Bupivacaine was released in vitro at a relatively constant rate over a period of ≈ 72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours.
Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.
为了减轻急性术后疼痛，开发了一种新的布比卡因缓慢释放配方。
将布比卡因以 60%（重量/重量）的比例微囊化在聚乳酸-共-羟基乙酸共聚物中，并对其物理化学性质和布比卡因释放动力学进行了表征。该制剂被注射到大鼠坐骨神经周围，以产生对脚趾夹捏的镇痛作用。在将布比卡因缓慢释放制剂置于同侧坐骨神经时，评估了大鼠足底外侧爪切口后的机械性痛觉过敏，持续 7 至 14 天，并与各种对照引起的痛觉过敏进行了比较。
布比卡因在体外以相对恒定的速率释放，持续约 72 至 96 小时。完全镇痛，表现为对脚趾夹捏无反应，持续 23 ± 7 小时，坐骨神经注射 0.4 mL 微球（释放 34 mg 布比卡因）后，半恢复时间为 42 ± 8 小时。0.5%（重量/体积）布比卡因-HCl（0.1 mL）溶液产生完全镇痛作用不到 2 小时，恢复半衰期为 2 小时。术后机械性痛觉过敏，表现为对冯·弗雷丝纤维的退缩反应增加，在 24 小时内消失，在 96 小时内低于对照组，当坐骨神经被布比卡因微球阻断时，而 0.5%布比卡因溶液仅能减少术后疼痛 4 小时。
与更长的功能阻断时间相对应，微球-布比卡因制剂能够显著降低术后疼痛，使其低于对照组水平长达 4 天。对于含有单一活性成分的可注射制剂，这种术后疼痛缓解数天的发现提供了一种改进的、有潜在前景的治疗方法，以预防手术后的急性疼痛。
