超滤在冠心宁注射液工艺中的应用及对有效成分的影响

选择适用于冠心宁注射液生产工艺的超滤膜,考察其对冠心宁注射液药液细菌内毒素和有效成分的影响。采用正交试验法考察不同孔径的超滤膜、操作压力、泵转数、药液温度对膜通量和细菌内毒素的影响;采用紫外可见分光光度法和HPLC法考察既定的超滤膜前后5批冠心宁注射液药液总酚酸含量及指纹图谱的变化情况。结果表明,当采用10 KD膜超滤、药液温度40℃左右、泵转速280 r/min、工作压力为0.05 MPa时,膜通量大,细菌内毒素降低明显;5批产品超滤膜前后的指纹图谱相似度在0.8以上,超滤膜后的药液总酚酸含量平均值为58 mg/mL,在可接受范围内。选择10 KD的超滤膜能有效降低冠心宁注射液中的细菌内毒素;膜的孔径对膜通量和细菌内毒素有显著影响;使用超滤对冠心宁注射液的整体化学成分影响不大,且有效成分含量符合冠心宁注射液质量要求。

Application on Guanxinning Injection in the Process of Ultra-filter and the Effect on Bioactive Components

To select the applicable ultrafiltration membrane for production process of Guanxinning injection,and inspect the effect on bioactive components and endotoxin of Guanxinning injection in the process of ultra-filter.The effect of the membrane flux and bacterial endotoxin was studied with four different membrane parameters（such as pore diameter of membrane,operational pressure,pump speed,the temperature of Guanxinning injection） by orthogonal test;and spectrophotometry and HPLC method were used to inspect the changes of total salvianolic acid content and fingerprint chromatogram,when the 5 batches of Guanxinning injection have been Ultra-filtered.Results showed that selecting the membrane of 10 KD,the ultrafiltration membrane had high membrane flux when the temperature of Guanxinning injection was 40 ℃,pump speed was 280 r/min,working pressure was 0.05 MPa,and endotoxin was significantly lower;All of the 5 batches of product after Ultra-filter,the fore and after Guanxinning injection were detection,the fingerprint chromatogram similarity was above 0.8 and the content of total salvianolic acid average was 58 mg/mL,within an acceptable range.The ultrafiltration membrane of 10 KD can be used to reduce bacterial endotoxin from Guanxinning injection effectively.The pore diameter of membrane have influences on membrane flux and endotoxin significantly.The use of ultrafiltration on Guanxinning injection has little effect on the overall chemical composition,which indicates that bioactive components meets the quality standard of Guanxinning injection.