长效缩宫素的生物效价测定方法研究  

Biological values of a long-acting oxytocin analog carbetocin

作　　者：谷舒怡[1] 黄坚[1] 唐黎明[1] 

机构地区：[1]上海市食品药品检验所,上海201203

出　　处：《药物分析杂志》2016年第1期165-170,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:对中国药典记载的缩宫素生物测定法进行改良,建立长效缩宫素的生物效价测定方法,考察长效缩宫素受体激动剂卡贝缩宫素的生物效价。方法:采用大鼠离体子宫平滑肌实验法。分别配制缩宫素标准品、巧特欣~(Duratocin~,卡贝缩宫素市售产品)和卡贝缩宫素至0.01 IU·mL^(-1)。试验中缩宫素标准品、巧特欣~选取0.42 mL、0.6 mL 2个体积,按随机区组设计的次序轮流注入dS_1、dS_2、dT_1、dT_2 4个剂量。每次注入dT_1或dT_2后,均注入2~3次dS_2和1次dS_1进行洗脱,观察子宫收缩幅度,当子宫对dS_1、dS_2产生的收缩幅度呈剂量相关时,继续进样,重复4组。按上述方法卡贝缩宫素选取0.44、0.6 mL 2个体积进行试验,记录各剂量所致子宫收缩的高度y(mm),按中国药典生物检定统计程序量反应平行线2.2法分析处理计算效价及实验误差。结果:3次试验回归显著(p<0.01),偏离平行不显著(p>0.05),可靠性测验通过。测得巧特欣~实际效价为10.316 IU·mg^(-1),平均可信限率为6.412%;同法测得卡贝缩宫素实际效价为8.962 IU·mg^(-1),平均可信限率为3.837%。结论:本试验在中国药典中缩宫素生物测定法的基础上,建立了长效缩宫素生物效价的测定方法并测定了缩宫素受体激动剂卡贝缩宫素的生物效价。Objective： To establish a method for measuring the biological potency of long-acting oxytocin, so as to supplement the Chinese pharmacopoeia oxytocin bioassay and evaluate the biological potency of carbetocin （ oxytocin receptor agonist ）. Methods： Rat uterine smooth muscle contraction models were established and used to evaluate the biological effects of the samples. Oxytocin Standard （ 0.01 IU · mL^-1 ） and the Duratocin （ 0.01 IU·mL^-1 ） were administrated with 0.42 mL and 0.6 mL respectively as dS1, dS2, dT1, dT2 groups by using randomized block method. During the above process, we added dS2 twice or three times and dSl once as eluent every time after adding dTl or dT2, and keep adding the following samples when the uterus recovered normal as indicated by the uterus contraction degree. Carbetocin （ 0.01 IU· mL^-1 ） and oxytocin standards （ 0.01 IU· mL^-1 ）were also taken with 0.44 mL and 0.6 mL respectively in another test. Each uterine contractions height y （ mm） was recorded and analyzed by Chinese pharmacopoeia reaction volume bioassay statistical procedures parallel lines 2.2 titer. Results： Reliability tests passed with a significant regression of the trial （p〈0.01 ）, and no significant deviation from the parallel （p〉O.05）. The fiducial limits of error （ FL ）was 6.412%, and the actual potency of Duratocin was 10.316 IU· mg^-1. The actual potency of carbetocinis was 8.962 IU ·mg^-1, with the FL as 3.837%. Conclusion： In this study, we established a method for measuring the biological potency of long- acting oxytocin, and successfully evaluated the biological potency of oxytocin receptor agonist carbetocin by this bioassay method.

关 键 词：缩宫素 卡贝缩宫素 生物效价 生物检定 离体子宫试验 标准改进 

分 类 号：R917[医药卫生—药物分析学]