Preparation and quality evaluation of human antithrombin-Ⅲ concentrate preparation
Objective To establish a process for manufacturing a concentrated human antithrombin-Ⅲ preparation from waste Cohn F Ⅳ precipitation and to evaluate the quality of the manufactured concentrated human antithrombin-Ⅲ prepara-tion by comparing the quality and related pharmacokinetic parameters with those of foreign marketed human antithrombin-Ⅲ products.Methods The manufactured human antithrombin-Ⅲ concentrated preparation and the foreign marketed human antithrombin-Ⅲ product Thrombate Ⅲ® were tested and compared for key quality attributes 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-Ⅲ concentrated preparation was 56.7 IU/mL,and the activity of Thrombate Ⅲ®was 53.4 IU/mL;the purity of the manufactured human antithrombin-Ⅲ concentrat-ed preparation was 99.1％,and of Thrombate Ⅲ®was 97.3％;the molecules with heparin affinity activity were about 89.1％in the manufactured human antithrombin-Ⅲ concentrated preparation molecule and 84.6％in the Thrombate Ⅲ®molecule;the specific activity of the manufactured human antithrombin-Ⅲ 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-Ⅲ concentrated preparation was 5.19 h in mice,which was slightly longer than that of the Thrombate Ⅲ®,which is 4.85 h;there was no statistically sig-nificant difference in the drug elimination rate between hAT-Ⅲ in the prepared human antithrombin-Ⅲ concentrate and hAT-Ⅲ in Thrombate Ⅲ® in mice serum(P=0.253 1).Conclu-sion Compared with Thrombate Ⅲ®,a similar product that has been marketed in foreign countries,all the key quality in-dexes of the manufactured human antithrombin-Ⅲ concentrated preparation are non-inferior to those of Thrombate Ⅲ®,indi-cating that the manufacturing process of human antithrombin-Ⅲ described herein is able to efficiently extract high-quality human antithrombin-Ⅲ preparation from waste Cohn F Ⅳ precipitation,and is able to improve the efficiency of comprehen-sive utilization of human plasma efficiently.
Human antithrombin-ⅢQuality controlHalf-lifeIsolation and purificationBlood plasma
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