超滤去除清开灵注射液中热原的研究

Remove of pyrogen by ultrafiltration from Qingkailing Injection

目的选择适用于清开灵注射液除热原的超滤膜。方法采用鲎试剂凝胶法,在对超滤膜除细菌内毒素性能初步筛选后,确定一种膜孔径用于清开灵注射液除热原。用含有热原的清开灵注射液通过选定的膜过滤,以热原检查法检查热原,验证超滤膜的除热原效果,并以指标性成分黄芩苷的转移率和膜通量对膜工艺条件进行筛选。结果用灵敏度0.06 EU/mL的鲎试剂检查,饮用水通过10 KD和30 KD的膜后符合注射用水内毒素标准要求,6批产品超滤前热原检查,3只家兔升温总和最低1.04℃,最高2.40℃,经过30 KD膜超滤后升温总和最低0.43℃,最高0.88℃,明显低于1.0℃;药液温度为40℃、泵转速250 r/min、操作压力为0.10～0.15 MPa时超滤通量最大,效率最高。结论选择30 KD的超滤膜能有效去除清开灵注射液中的热原,药液温度、泵转速对膜通量有显著影响,超滤后黄芩苷的转移率为97.15%,指标性成分含量符合清开灵质量标准。

Objective To select the ultrafiltration membrane for removing pyrogen from Qingkailing Injection.Methods The tachypleus amebodyte lysate（TAL）-gel method was used to determine a pore size of ultrafiltration membrane for removing pyrogen from Qingkailing Injection after initial screening of the capability of the membrane in elimination of bacterial endotoxin.The pyrogen was detected by pyrogen test to verify the effect of pyrogen elimination of the membrane when Qingkailing Injection passed through.The processing condition of the membrane was screened based on the transfer rate and membrane flux of baicalin（index constituent）.Results TAL with the sensitivity of 0.06 EU/mL was used in the membrane examination.The drink water was changed to meet the standard of injection water after passing through the membrane of 10 KD and 30 KD.In the pyrogen examination of 6 batches of Qingkailing Injection before ultrafiltration the minimum sum of elevated temperature was 1.04℃and maximum was 2.40℃in three rabbits.After ultrafiltration by the membrane of 30 KD the minimum sum of elevated temperature was 0.43℃and maximum was 0.88℃, which was significantly lower than 1.0℃.When the temperature of Qingkailing Injection was 40℃,pump speed was 250 r/min,and working pressure was 0.10-0.15 MPa,the ultrafiltraion flux was the highest with maximum efficient.Conclusion The ultrafiltration membrane of 30 KD can be used to eliminate pyrogen from Qingkailing Injection effectively.The temperature and pump speed have influences on membrane flux significantly.The transfer rate of baicalin is 97.15%after ultrafiltration,which indicates that the content of index constituent meets the quality standard of Qingkailing Injection.