狂犬病疫苗的吡喹酮乳化稀释剂研制

发布时间：2018-04-08 22:01

本文选题：犬　切入点：狂犬病　出处：《内蒙古农业大学》2016年硕士论文

【摘要】：狂犬病和一些犬绦虫病,如细粒棘球绦虫病等,是与家畜和人相关的重要人兽共患病,严重威胁着畜牧业发展并危害着人类的健康。犬既是狂犬病的主要传染源,同时也是细粒棘球蚴绦虫的终末宿主。因此,研究一种狂犬病疫苗和驱虫药的复合剂,在免疫狂犬病的同时,还能够驱除犬绦虫,尤其是细粒棘球绦虫,将具有很大的临床实际意义。为此,本研究在前期的工作的基础上,进行了狂犬病疫苗的吡喹酮乳化稀释剂研究,对复合剂做了进一步改进。首先,为了摸清呼和浩特市流浪犬携带狂犬病病原以及感染绦虫的情况,我们对市区流浪狗展开了狂犬病抗原和犬绦虫感染情况的调查。结果显示,呼和浩特市流浪犬狂犬病病毒携带率为13.4%,绦虫感染率为52.6%。其次,为了解决水分散性疫苗和脂溶性吡喹酮不相溶的矛盾,本研究通过筛选乳化剂、抗冻剂、粘度调节剂种类并确定各助剂的用量,成功制备出性质稳定的吡喹酮水乳剂,并对制备工艺进行响应面法优化。然后对吡喹酮水乳剂进行质量检测分析,结果显示吡喹酮有效含量为20±0.02mg/mL,用于制备的复合剂稳定性良好,符合产品各项指标要求。此外,本研究对毗喹酮水乳稀释剂制备的狂犬病疫苗复合剂进行了稳定性测定以及药代动力学和毒理学研究。结果表明复合剂血药达峰时间为120min,半数致死量LD50=232mg/kg。通过刺激性实验说明,其对受药动物刺激性小,对肝。肾组织均无损伤。最后对复合剂进行临床试验研究,结果证实复合剂驱虫率达到92.8%,狂犬病抗体产生率达到89.3%,证明复合剂具有同时免疫狂犬病和驱绦虫的效果。
[Abstract]:Rabies and some canine tapeworm, such as Echinococcus granulosus, are important zoonosis related to domestic animals and human beings, which seriously threaten the development of animal husbandry and endanger human health.Dogs are not only the main source of infection of rabies, but also the terminal host of Echinococcus granulosus.Therefore, it is of great clinical significance to study a combination of rabies vaccine and insect repellent, which can also kill canine tapeworm, especially Echinococcus granulosus.Therefore, based on the previous work, the praziquantel emulsified diluent of rabies vaccine was studied, and the compound agent was further improved.Firstly, in order to find out the rabies pathogen and the infection of tapeworm in the stray dogs in Hohhot, we investigated the rabies antigen and the infection of tapeworm in the stray dogs in the urban area.The results showed that the carrying rate of rabies virus was 13.4 and the infection rate of tapeworm was 52.6in Hohhot.Secondly, in order to solve the contradiction between water-dispersible vaccine and fat-soluble praziquantel, the stable praziquantel water emulsion was successfully prepared by screening emulsifier, antifreeze, viscosity regulator and determining the dosage of each adjuvant.The preparation process was optimized by response surface method.The results showed that the effective content of praziquantel was 20 卤0.02 mg / mL.In addition, the stability, pharmacokinetics and toxicology of rabies vaccine compound prepared by piqualone emulsion diluent were determined.The results showed that the peak time of blood drug was 120 min and LD50 mg / kg.The experimental results show that it is less irritating to the animals and less to the liver.No injury was found in renal tissue.Finally, the clinical trial of the compound agent was carried out. The results showed that the compound agent repellent rate reached 92.8%, and the rabies antibody production rate reached 89.3%, which proved that the compound agent had the effect of simultaneously immunizing rabies and tapeworm.
【学位授予单位】：内蒙古农业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：S859.79

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