雏鸭肝炎注射用蟾酥缓释制剂的研制

发布时间：2018-06-27 23:40

  本文选题：蟾酥 + 温敏凝胶　； 参考：《山东中医药大学》2015年硕士论文

【摘要】：目的:以中药蟾酥为模型药物,制备用于治疗雏鸭肝炎的新型肌内注射用温敏型制剂,对其制备工艺、凝胶中药效学成分的体外释放规律、质量标准进行考察研究,并对该凝胶制剂稳定性及雏鸭病毒鸭肝炎在体药效学进行初步研究。方法:以药学指标筛选模型药物蟾酥的工艺制备路线;采用正交试验法,多指标优选制备工艺路线参数;以蟾酥为主药,在参考文献的基础上,采用温敏型辅料P407、P188,粘度调节剂MC、HPMC、SA、PEG4000等,以凝胶温度和体外释放速率为指标对制剂的处方组成进行筛选。采用“冷溶法”制备空白及含药凝胶,以“搅拌子法”测定不同处方温敏凝胶的胶凝温度。采用透析袋-浆法,测定并计算药物的体外累计释药百分率,绘制累计释药百分率时间曲线。将数据用零级释药方程、一级释药方程、Higuchi方程进行拟合,对药物的释放机理进行研究。采用高效液相色谱法对新型制剂中的华蟾酥毒基和脂蟾毒配基进行了含量测定,并通过其于蟾酥注射液、西药金刚烷胺粉剂比较在体肌注射疗效,对该制剂药效学进行初步研究。结果:模型药物中药蟾酥优选的制备工艺路线为:蟾酥90%乙醇回流3次,每次加入量为8,6,6,每次1 h,过滤,合并滤液,滤液浓缩至0.5 g生药/m L。温敏制剂最佳处方为:蟾酥浓缩液-P407-P188-HPMC-PEG4000(0.08:20:2:0.5:0.5)。该处方下,制剂的胶凝温度约为38.8℃。体外释放结果表明,温敏凝胶中有效成分释放量逐渐增高,在12天时药物累计释放90%以上,说明所制备的温敏凝胶对模型药物蟾酥中有效成分具有明显的缓释作用。释药模型拟合符合Higuchi模型。通过定量分析,确定华蟾酥毒基和脂蟾毒配基含量总量不得低于15μg/ml。在体药效学结果表明:蟾酥注射液存活率为74.3%,西药金刚烷胺粉剂存活率为68.6%,蟾酥温敏型注射液存活率为82.9%,三组进行卡方检验后,Pearsonx2=1.943,df=2,P=0.379(0.05),三种方法治疗鸭病毒性肝炎效果没有显著性差异,但是在实际实验进程中,由于蟾酥注射液及金刚烷胺粉剂注射次数较多,引起鸭的应激反应,鸭体重的下降,而蟾酥温敏型注射液组并没有相关症状。结论:以上各项体内外实验证明,制备的蟾酥温敏凝胶胶凝温度适宜,制剂均匀稳定,质量控制方法准确,重现性良好;温敏凝胶经肌内注射给药后,能明显延缓中药蟾酥中有效成分的释放,不仅能够提高药物的生物利用度,而且降低其毒副作用,同时蟾酥温敏凝胶展现出良好的肌内注射应用前景,制备工艺稳定。
[Abstract]:Objective: to prepare a new type of thermo-sensitive preparation for intramuscular injection for the treatment of ducklings hepatitis with toad as model drug, and to investigate the preparation process, in vitro release rule of pharmacodynamic components in the gel and the quality standard. The stability of the gel and the pharmacodynamics of duck virus hepatitis in vivo were studied. Methods: the preparation route of the model drug was screened by pharmacological index, the parameters of the preparation process were optimized by orthogonal test, the main drug was toad cake, and based on the references, The temperature sensitive excipient P407 P188, the viscosity regulator MCHPMCSAPEG4000 and the gel temperature and release rate in vitro were used to screen the formulation of the preparation. The blank and drug-containing gels were prepared by "cold dissolution method", and the gelation temperature of thermo-sensitive gels with different prescriptions was determined by "agitation method". The cumulative drug release percentage in vitro was measured and calculated by dialysis bag-serous method, and the time curve of cumulative drug release percentage was plotted. The data were fitted with zero-order drug release equation and first-order drug release equation Higuchi equation to study the mechanism of drug release. The contents of bufo venom and bufagin ligand in the new preparation were determined by high performance liquid chromatography (HPLC), and the efficacy of intramuscular injection of amantadine powder was compared with that of bubufen injection. The pharmacodynamics of the preparation was preliminarily studied. Results: the optimal preparation route of the model drug Chinese medicine toad was as follows: the reflux of 90% ethanol was 3 times, the amount of each addition was 8 ~ 6 ~ 6, 1 hour each time, filtration, combined filtrate, filtrate was concentrated to 0.5 g crude drug / L ~ (-1) 路m ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1). The best formulation of temperature sensitive preparation is toad crisp concentrate-P407-P188-HPMC-PEG4000 (0.08: 20: 2: 0.5: 0.5). The gelation temperature of the preparation is about 38.8 鈩，

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