人凝血酶原复合物冻干保护剂及冻干工艺的研究

Lyoprotectants and freeze-drying process of human prothrombin complex concetrate

目的对人凝血酶原复合物冻干保护剂及冻干工艺进行研究,生产出符合中国药典要求的产品,提高人凝血因子Ⅸ回收率。方法通过对冻干保护剂甘氨酸不同添加浓度的研究比较,得到最佳的甘氨酸添加浓度;探讨不同冻干工艺对人凝血酶原复合物的影响,优化得到最佳冻干工艺。结果冻干保护剂甘氨酸的最佳添加浓度为20 g·L^(-1);最佳冻干工艺为:制品快速降温到-45.0℃保持3 h冻结,退火到^(-1)5℃,再冻结,保持3 h后,抽真空,真空度保持在10 Pa左右后,开始加热,升温至0℃升华;升华完毕,梯度升温(每小时升高10~20℃);制品温度升至30℃后,制品进入干燥最后阶段,保持数个小时,温度不超过35℃。结论通过对人凝血酶原复合物处方及冻干工艺进行优化,制备出了符合中国药典要求的冻干产品,人凝血因子Ⅸ收率提高了约18%。

Objective To produce human prothrombin complex concetrate meeting the Chinese Pharmacopoeia and improve the recovery rate of human coagulation factor Ⅸ by studying lyoprotectants and freeze-drying process. Methods We chose glycine as the lyoprotectant, compared the different contents, and got the best content of glycine. For the best freeze-drying process, we explored the effect of different freeze-drying processes for human prothrombin complex concetrate. Results The best content of glycine was 20 g·L-1; the best lyophilization process was quickly freezing the product to- 45.0 ℃ and holding for 3 h; annealing it to-15 ℃; refreezing it and holding for another 3 h before vacuumization and heating it when the vacuum was kept at about 10 Pa; the sublimation started while the temperature reached 0 ℃ and gradiently escalated 10- 20 ℃ per hour after the sublimation. When temperature of the product reached 30 ℃, the final stages of drying began. Hold for a few hours, and making sure the temperature of the product did not exceed 35 ℃. Conclusion By optimizing prescription and freeze-drying process of human prothrombin complex concetrate, the product meets the requirements of Chinese Pharmacopoeia, the recovery rate of human coagulation factor Ⅸ has increased about 18%.