摘要
目的建立一种从废弃的Cohn法组份IV沉淀中提取制备人抗凝血酶Ⅲ浓缩制剂的工艺,并通过与国外已上市人抗凝血酶-Ⅲ产品进行质量及相关药代动力学参数对比,评价制备的人抗凝血酶-Ⅲ浓缩制剂的质量情况。方法对制备的人抗凝血酶-Ⅲ浓缩制剂和国外已上市人抗凝血酶-Ⅲ产品ThrombateⅢ^(®)进行活性、纯度、肝素亲和力等关键质量属性的检测对比,并进行小鼠体内消除半衰期对比研究,评价2种制品的质量相似性。结果制备的人抗凝血酶-Ⅲ浓缩制剂活性为56.7 IU/mL,ThrombateⅢ^(®)活性为53.4 IU/mL;制备的人抗凝血酶-Ⅲ浓缩制剂的纯度为99.1%,ThrombateⅢ^(®)的纯度为97.3%;制备的人抗凝血酶-Ⅲ浓缩制剂中具肝素亲和活性的分子约为89.1%,ThrombateⅢ^(®)分子中具肝素亲和活性的分子约为84.6%;制备的人抗凝血酶-Ⅲ浓缩制剂的比活为10.98 IU/mg,ThrombateⅢ^(®)的比活为9.98 IU/mg;制备的人抗凝血酶-Ⅲ浓缩制剂在小鼠体内的消除半衰期为5.19 h,ThrombateⅢ^(®)在小鼠体内的消除半衰期为4.85 h;经t检验分析,制备的人抗凝血酶-Ⅲ浓缩制剂中的hAT-Ⅲ与ThrombateⅢ^(®)中的hAT-Ⅲ在小鼠血清中的药物消除速率差异无统计学意义(P=0.2531)。结论与国外已上市同类产品ThrombateⅢ^(®)相比,制备的人抗凝血酶-Ⅲ浓缩制剂的各项关键质量指标均非劣于ThrombateⅢ^(®)说明本文所述人抗凝血酶-Ⅲ的制备工艺能有效从废弃的Cohn法组份IV沉淀中提取高质量的人抗凝血酶-Ⅲ制剂,能有效提高人血浆综合利用效率。
Objective To establish a process for manufacturing a concentrated human antithrombin-Ⅲpreparation from waste Cohn F IV precipitation and to evaluate the quality of the manufactured concentrated human antithrombin-Ⅲpreparation by comparing the quality and related pharmacokinetic parameters with those of foreign marketed human antithrombin-Ⅲproducts.Methods The manufactured human antithrombin-Ⅲconcentrated preparation and the foreign marketed human antithrombin-Ⅲproduct ThrombateⅢ^(®)were tested and compared for key quality atributes such as activity,purity,heparin affinity,etc.,and an in vivo mouse elimination half-life comparative study was conducted to evaluate the quality similarity of the two products.Results The activity of the manufactured human antithrombin-Ⅲconcentrated preparation was 56.7 IU/mL,and the activity of ThrombateⅢ^(®)was 53.4 IU/mL;the purity of the manufactured human antithrombin-Ⅲconcentrated preparation was 99.1%,and of Thrombate was 97.3%;the molecules with heparin affinity activity were about 89.1%in the manufactured human antithrombin-Ⅲconcentrated preparation molecule and 84.6%in the ThrombateⅢ^(®)molecule;the specific activity of the manufactured human antithrombin-1II concentrated preparation was 10.98 IU/mg,and that of Thrombate III?was 9.98 IU/mg;and the half-life of the manufactured human antithrombin-l concentrated preparation was 5.19 h in mice,which was slightly longer than that of the ThrombateⅢ^(®)which is 4.85 h;there was no statistically significant difference in the drug elimination rate between hAT-Ⅲin the prepared human antithrombin-Ⅲconcentrate and hAT-Ⅲin ThrombateⅢ^(®)in mice serum(P=0.2531).Conclusion Compared with Thrombate I,a similar prodiuct that has been marketed in foreign countries,all the key quality indexes of the manufactured human antithrombin-Il concentrated preparation are non-inferior to those of Thrombate I,indicating that the manufacturing process of human antithrombin-Ⅲdescribed herein is able to efficiently extr
作者
郭玉婷
付艳丽
孔涛
马亚茹
梁凌宇
陈勇
GUO Yuting;FU Yanli;KONG Tao;MA Yaru;LIANG Lingyu;CHEN Yong(Lanzhou Institue of Biological Products Co.,Ltd.,Gansu Provincial Vaccine Technology Innovation Center,Lanzhou 730046,Gansu Province,China)
出处
《微生物学免疫学进展》
CAS
2024年第3期45-51,共7页
Progress In Microbiology and Immunology
关键词
人抗凝血酶-Ⅲ
质量控制
半衰期
分离和纯化
血浆
Human antithrombin-Ⅲ
Quality control
Half-life
Isolation and purification
Blood plasma
