氢氧化铝佐剂配制工艺的优化

Optimization of Procedure for Preparation of Aluminium Hydroxide Adjuvant

目的优化氢氧化铝[A(lOH)3]佐剂配制工艺。方法对A(lOH)3配制工艺中的反应温度、氢氧化钠(NaOH)溶液的滴入速度、气体流量和反应终点pH值进行优化,观察配制的A(lOH)3溶液的状态。分别以原工艺和优化工艺配制的A(lOH)3溶液为佐剂制备重组乙型肝炎疫苗(CHO细胞),比较二者的外观和效力。结果优化的A(lOH)3配制工艺为:反应温度70～72℃;NaOH溶液滴入速度185ml/min,10个点滴入;气体流量0.2bar;反应终点pH值5.80±0.05,以该工艺配制的A(lOH)3胶体颗粒大小均匀,呈淡淡的蓝白色,不发生沉淀。以优化工艺配制的A(lOH)3溶液为佐剂制备的重组乙型肝炎疫苗(CHO细胞)无沉淀,为均匀的胶体,成品放置3年外观无显著变化;疫苗效力略有提高,但不显著。结论优化了A(lOH)3溶液佐剂的配制工艺。

Objective To optimize the procedure for preparation of aluminium hydroxide adjuvant. Methods The temperature, speed for adding sodium hydroxide dropwise, air flow as well as pH value at reaction endpoint were optimized, and the state of aluminium hydroxide adjuvant solutions prepared by the optimized procedure was compared with that by the original procedure. Re-combinant hepatitis B（HB）vaccine（CHO cells）was prepared using the aluminium hydroxide solutions formulated by the optimized and original procedures as adjuvant respectively, and the appearances and potencies were compared. Results The optimal tempera-ture, speed for adding sodium hydroxide dropwise, air flow and pH value at reaction endpoint were 70 ～ 72℃, 185 ml / min at ten points, 0. 2 bar and 5. 80 ± 0. 05 respectively. The aluminium hydroxide colloidal particles were slightly bluish white, even in size and free from precipitate. The recombinant HB vaccine using the aluminium hydroxide solution prepared by the optimized procedure as adjuvant was an even colloid free from precipitate, of which the appearance of final product showed no significant change after storage for 3 years, while the potency increased slightly but showed no significant difference with that using the aluminium hydroxide prepared by the original procedure as adjuvant. Conclusion The for preplaration of aluminium hydroxide adjuvant was optimized procedurey.