【作者】 吴雨龙；

【导师】 鞠玉琳；

【作者基本信息】 延边大学 ， 基础兽医学， 2007， 硕士

【摘要】 中药复方肠宁Ⅱ（CNⅡ）是针对动物细菌性腹泻而研制的复方制剂。该药能有效的抑制大肠杆菌等病原体的增长繁殖，降低其致病力，减缓动物肠蠕动，对动物腹泻的防治具有很好的疗效。但本药味苦，不易饲喂，在GI（胃肠）液中稳定性不高，不易贮存，且给药次数频繁，为提高该药的稳定性，减少给药次数，并达到血药浓度平稳，增强对患病动物临床治疗的效果，本试验将其制成缓释制剂，使其包藏于β-环糊精（β-cyclodextrin，β-CD）分子内，以提高CNⅡ的稳定性，掩盖其苦味，减少给药次数，达到血药浓度平稳。包括缓释制剂的制备试验、缓释制剂的含量测定试验、薄层色谱试验、药效学试验、体外释药试验、体内释药试验。以苦参碱含量为指标，在反应温度50℃，反应时间4h，CNⅡ和β-CD投料比为1：3以及搅拌速度为1500r／min时所形成的缓释制剂为最佳；缓释制剂经显微镜观察、药效学试验等方法鉴定，证明包合成功；缓释制剂中药物的平均含量为35.56±0.12％；将β-CD·CNⅡ缓释制剂的体外释药结果拟合为零级释放速率过程，释放动力学函数关系用方程式表示为Y=6.5716X+9.8374，r=0.9932；将β-CD·CNⅡ体外释药结果用时间平方根模型进行拟合，求出Huguchi方程，方程为Y=25.903t^1/2-7.574，r=0.9882；以消除相对时间对浓度的对数进行线形回归，得斜率乘以2.303，为消除速度常数Ke，消除半衰期T_1/2=0.693/Ke，药-时曲线下面积AUC_0～24；采用梯形法计算，峰浓度Cmax与达峰时间Tmax为实测值，结果中药CNⅡ组代谢参数为：Tmax=3±0.17h，Cmax=26.79±6.12ug／ml，AUC_0～24=20.47±2.3ug／ml，MRT=3.48±0.09h；缓释制剂β-CD·CNⅡ组Tmax=5±0.25 h，Cmax=22.45±5.21 ug／ml，AUC_0～24=9.88±0.21ug／ml，MRT=5.50±0.12h，经配对t检验，β-CD·CNⅡ与CNⅡ的Cmax与AUC_0～24无显著差异，而达峰时间为CNⅡ的1.67倍，体内平均滞留时间（MRT）有极显著差异（P＜0.01）。上述结果表明，按最优条件制备的中药β-CD·CNⅡ不仅能对大肠杆菌K₉₉有良好的体外抑菌作用，能显著抑制小肠蠕动，且相对于CNⅡ具有缓释特征。更多还原

【Abstract】 Chinese traditional medicine "CNⅡ" is a compound medicine which is aim directly at bacterial diarrhea ofanimal. "CNⅡ"can inhibit the growth and multiplication of E. coli, reduce the virulence, slow down the animals’enterokinesia, it has good curative effect to prevent and cure the bacterial diarrhea of animal. But "CNⅡ"bitterin taste, it’s difficult to feed, it’s not stability in GI, it’s not easy to storage, it must be given medicine frequently.In order to improve the stability of the medicine, reduce the giving number of times, reach the blood drug levelstability, increase the effect of sick animal in clinic, the test makes the medicine, into sustained releasepreparation, it makes the medicine be contained inβ-CD. So it can improve the stability, cover up themedicine’s bitter, reduce the giving number of times and keep the blood drug level stability. The experimentcontains the test of preparing the sustained release preparation, the test of assaying of sustained releasepreparation, the test of TLC, the test of pharmacodymaies, the test of releasing medicine in vitro, the test ofreleasing medicine in vivo.As the content of matrine index, in 50℃, 4h, CNⅡ:β-CD=1:3,can make out the best sustained releasepreparation; after the way of observation of microscope and the test of pharmacodynamics, the result indicate itwas succeed in clathration; the average content of sustained release preparation is 35. 564±0.12％; let the result ofsustained release preparation fit as zero order release, it can indicate as a functional relation equation:Y=6.5716X+9.8374, r=0.9932; let the result of sustained release preparation fit as the model of time square, theHuguchi equation: Y=25.903t^1/2-7.574,r=0.9882; using the trapezoidal rule to calculate, the Cmax and Tmaxwere true results, the metabolism parameter of the group of CNⅡwere: Tmax=3±0.17h, Cmax=26.79±6.12ug/ml, AUC_0～24=20.47±2.3ug/ml, MRT=3.48±0.09h; the group of sustained release preparationwere: Tmax=5±0.25 h, Cmax=22.454±5.21ug/ml, AUC_0～24=9.88±0.21ug/ml, MRT=5.50±0.12h;afier t analysis,the Cmax and AUC_0-24 ofβ-CD’CNⅡhave no significant deviation with CNⅡ（P＞0.05）, but the Tmax was as1.67 than CNⅡ, they have very significant deviation in MRT （P＜0.01）.The results indicate that the sustained release preparation of Chinese traditional compound medicine CNⅡhas the properly of sustained release compare with CNⅡ.更多还原