人用疫苗氢氧化铝佐剂吸附力的质量控制初探

Preliminary exploration of quality control on adsoption capacity of aluminum hydroxide adjuvant for human vaccine

目的 建立氢氧化铝佐剂吸附力的相关质控方法.方法 对3批国产氢氧化铝佐剂与丹麦铝佐剂（Alhydrogel）同时进行粒径、比表面积、零电荷点的测定,并比较两种佐剂对不同浓度牛血清白蛋白（bovine serum albumin,BSA）及百日咳丝状血凝素（filamentous hemagglutinin,FHA）的吸附力.结果 测定显示,3批国产铝佐剂50％体积百分比（DV50）的粒径分布分别为4.49、5.83和6.28 μm;比表面积分别为1 602、1 093和1 014 m^2/kg;零电荷点分别为10.2、10.3和10.2.丹麦铝佐剂DV50的粒径为4.58 μm,比表面积为2 230 m^2/kg,零电荷点为8.5.3批国产和1批丹麦铝佐剂（5 g/L）对2 g/L BSA的吸附率分别为98.69％、99.41％、99.72％和98.04％,均符合欧洲药典的吸附力合格标准.国产和丹麦铝佐剂（1.3 g/L）对50～1 000 mg/L FHA的吸附率均在97％以上.结论 根据对国产氢氧化铝佐剂相关质量指标的研究,初步建立了氢氧化铝佐剂吸附力的质控标准.

Objective To establish the quality control method for adsorption capacity of aluminum hydroxide adjuvant in vaccine.Methods The grain size,specific surface area and zero charge point of domestic and Denmark aluminum hydroxide adjuvants were measured,and the adsorption capacity of both aluminum hydroxide adjuvants to different concentration of BSA and FHA were compared.Results The grain sizes of DV50 for 3 lots of domestic aluminum hydroxide adjuvant were 4.49,5.83 and 6.28 μm,respectively,and 4.58 μm for Denmark Alhydrogel.The specific suface areas were 1 602,1 093 and 1 014 m^2/kg for 3 lots of domestic aluminum hydroxide adjuvant,respectively,and 2 230m^2/kg for Denmark Alhydrogel.Zero charge points were 10.2,10.3 and 10.2 for 3 lots of domestic aluminum hydroxide adjuvant,respectively,and 8.5 for Denmark Alhydrogel.The adsorption capacities of 3 lots of domestic aluminum hydroxide adjuvant （5 g/L） to 2 g/L BSA were 98.69%,99.41% and 99.72%,respectively,and 98.04% for Denmark Alhydrogel （5 g/L）,both met the requirement of standard in European Pharmacopoeia.The adsorption capacities of both domestic aluminum hydroxide adjuvant and Denmark Alhydrogel （1.3 mg/L） to 50-1 000 mg/L FHA were above 97%.Conclusion Series of parameters for quality control are established to evaluate the adsorption capacity of domestic aluminum hydroxide adjuvant according to the study on relative quality indexes of domestic aluminum hydroxide adj uvant.