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目的:对肠道病毒71型灭活疫苗生产工艺中氢氧化铝佐剂的制备工艺进行优化。方法:采用氨水法制备氢氧化铝佐剂,取优化前3批及优化后3批,对制备过程中氨水的滴加方式以及透析方式进行优化;检测优化前后的氢氧化铝佐剂的粒径、沉降率、铵离子及铝含量,同时检测优化前后各3批氢氧化铝对肠道病毒71型灭活疫苗的吸附效果。结果:优化后的氢氧化铝佐剂平均粒径显著小于优化前(P<0.05),且平均粒径变异系数小于优化前3批,优化后3批氢氧化铝佐剂的沉降率均为0 m L,铵离子检测合格率100%,铝含量及氢氧化铝含量显著大于优化前(P<0.05)、分别提高了24.7%和26.1%;优化前后6批氢氧化铝佐剂所配制的半成品,其上清液抗原百分含量均≤1.25%,优化前后的氢氧化铝佐剂对EV71抗原的吸附效果比较,差异无统计学意义(P>0.05)。结论:本部分的优化方式提高了自配氢氧化铝佐剂的质量和安全性,减少了批间差异,提高了生产效率,并且其有效性没有因为优化而受到影响。
Objective: To optimize the preparation process of aluminum hydroxide adjuvant in the production process of enterovirus 71 inactivated vaccine. Methods: Ammonia hydroxide was used to prepare aluminum hydroxide adjuvant. The optimum conditions were as follows: the first three batches of the adjuvant and the third batch of the three batches after optimization were used to optimize the dropping method and the dialysis mode of aqueous ammonia during the preparation. The particle size of the aluminum hydroxide adjuvant before and after optimization , Sedimentation rate, ammonium ion and aluminum content. At the same time, the adsorption effect of three batches of aluminum hydroxide on the enterovirus 71 inactivated vaccine was tested before and after optimization. RESULTS: The average particle size of the optimized aluminum hydroxide adjuvant was significantly lower than that before optimization (P <0.05), and the coefficient of variation of average particle size was less than that of the first three batches. The optimal sedimentation rate of three aluminum hydroxide adjuvants was 0 m L, ammonium ion detection pass rate of 100%, aluminum content and aluminum hydroxide content was significantly greater than before optimization (P <0.05), respectively, an increase of 24.7% and 26.1%; before and after optimization of six batches of aluminum hydroxide adjuvant prepared semi-finished products , The percentage of supernatant antigens were all less than 1.25%. There was no significant difference in the adsorption of EV71 between the two drugs before and after the optimization (P> 0.05). CONCLUSIONS: The optimization of this section improves the quality and safety of self-formulated aluminum hydroxide adjuvants, reduces batch-to-batch differences and increases production efficiency without compromising optimization.