布比卡因聚乳酸微球在家兔体内的缓释效应(英文)

Pain-alleviating effect of bupivacaine polylactic acid microspheres in rabbits

背景:布比卡因广泛应用于治疗及缓解因手术、炎症、肿瘤等引起的急、慢性疼痛,其镇痛作用时间不能满足临床对药物缓慢释放延长镇痛时间的要求。目的:采用高效液相色谱法和仿豚鼠皮丘法,检测以高分子聚合物——聚乳酸为载体制成的布比卡因聚乳酸微球在家兔体内所具有的缓释效应。设计:完全随机对照动物实验。单位:解放军第二军医大学药学院。材料:新西兰兔16只,体质量(2.58±0.17)kg。干预:实验于2002-09/11在解放军第二军医大学药学院药剂教研室完成。①采用仿豚鼠皮丘法建立动物模型。①新西兰兔16只,随机分为两组,每组8只。注射组皮下注射布比卡因注射液5mg/kg;微球组皮下植入布比卡因微球5mg/kg。注射组兔于射液后5,10,20,30,45min,1,2,3,4,6,8,12,24h及微球组兔于给药后0.5,1,2,3,4,5,6,8,12,24,36,48和60h耳缘静脉采血1.5mL进行指标测定。③高效液相色谱法测定血浆中布比卡因浓度及进行药物缓释作用测定。主要观察指标:血浆中布比卡因浓度的变化和局麻药作用直径。结果:16只兔进入结果分析。①血药浓度变化结果:注射组血药浓度迅速达到峰值,且浓度较高,为2.4664mg/L,随后浓度快速下降。微球组血药浓度相对较平稳,达峰较晚,峰浓度=0.7781mg/L,且血药浓度一直维持较低水平,平均滞留时间明显延长(P<0.05)。②药效缓释作用结果:发现布比卡因微球组的镇痛作用时间较布比卡因注射液组明显延长(P<0.05)。结论:布比卡因微球制剂在家兔体内具有缓慢释放镇痛效应的作用。

BACKGROUND： Bupivacaine is widely used to alleviate post-operatlon pain and cure acute and chronic pain caused by inflammation or cancer. Its analgesic time cannot meet the request that drug is released slowly to prolong the analgesic time in clinic. OBJECTIVE： To detect the alleviating effect of bupivacaine polylactic acid microspheres taking high molecular polymer-polylactic acid as vector in rabbits with high performance liquid chromatograph （HPLC） and traditional skin test method. DESIGN： A completely randomized controlled animal experimental study. SETTING： School of Pharmacy, Second Military Medical University Of Chinese PLA MATERIALS： Sixteen New Zealand rabbits, weighing （2.58±0.17）kg were used in this experiment. INTERVENTIONS： The experiment was carried out at the Department of pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA between September and November 2002. （1） Animal models were established according to traditional skin test method. （2） Totally 16 New Zealand rabbits were randomly divided into 2 groups ： Group A and Group B, with 8 in each one. 5 mg/kg bupivacaine parenteral solution was injected subcutaneously in Group A, 5 mg/kg hupivacaine polylactic acid microspheres were implanted between subcutaneous tissue and sarcolemma in Group B. We took 1.5 mL blood from ear border vein at 5, 10, 20, 30, 45 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after administration of bupivacaine parenteral solution respectively in Group A and another 1.5 mL at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 3 6, 48 and 60 hours after admistration of bupivacaine microsphere powder for index detection. （3） HPLC method was used to detect the concentration and releasing effect of bupivacaine in blood serum. MAIN OUTCOME MEASURES： Concentration change of bupivacaine in blood serum and efficacy diameter of local anesthetic. RESULTS：All the 16 rabbits entered the stage of result analysis. （1） Change of bupivacaine concentration： Plasma bupivacaine concentration in Group A reached the peaked quickly after subutaneous injection with the high concentration of 2.466 4 mg/L, then declined quickly. Plasma bupi- vacaine concentration in Group B was relative stable, reached a peak much slowly a/ter subcutaneous implantation, with peak concentration of 0.778 1 mg/L, and the plasma bupivacaine concentration maintained a relative low level, the mean retention time was obviously prolonged （P 〈 0.05）. （2） Alleviating effect of bupivacaine： The analgesic time was significantly longer in the bupivacaine microspbere group than in the bupivacaine parenteral solution group （P 〈 0.05）. CONCLUSION： Bupivacaine polylactic acid microspheres have sustained release effects in rabbits.