国产盐酸洛美沙星滴眼液中抑菌剂使用现状分析

目的：分析国产盐酸洛美沙星滴眼液抑菌剂使用现状以及存在的问题。方法：采用《中华人民共和国药典》（简称《中国药典》）2015年版四部《1121抑菌效力检查法》、自建的盐酸洛美沙星滴眼液抑菌剂含量检查方法、冻融实验、pH和包装材料对于抑菌剂的影响实验等，对来自13家企业138批产品中的6种抑菌剂进行检测，确定该产品是否需要加入抑菌剂以及抑菌剂加入的种类和用量的合理性。结果：处方中未添加抑菌剂的2个厂家以及5个添加抑菌剂的厂家产品达不到《中国药典》规定的抑菌效力标准；抑菌剂含量检查中，1个厂家1批次羟苯乙酯、1个厂家1批次三氯叔丁醇以及1个厂家4批次硫柳汞含量不符合规定。冻融实验结果显示，高浓度的羟苯乙酯会在低温环境下促使盐酸洛美沙星结晶析出。另外，产品pH和低密度聚乙烯塑料包装瓶均影响溶液中三氯叔丁醇的稳定性；同时低密度聚乙烯塑料包装对于硫柳汞还存在吸附作用。结论：目前国产盐酸洛美沙星滴眼液中抑菌剂的使用种类和用量均存在一定问题，建议企业兼顾生物学评价和理化评价对处方进一步优化。

Objective: To investigate the current situation and to analyze the existing problems of the antimicrobial agents used in domestic lomefloxacin hydrochloride eye drops. Methods: In order to evaluate the necessity of antimicrobial agents to be added in lomefloxacin hydrochloride eye drops,and the rationality of variety and dosage of antimicrobial agents,138 batches of lomefloxacin hydrochloride eye drops from 13 manufacturers had been analyzed by the antimicrobial effectiveness test in the Chinese Pharmacopoeia(2015 edition,volume 4,1121),the quantitative methods for these antimicrobial agents developed by the author and freeze-thaw test. The influence of pH and packaging materials on these antimicrobial agents was also studied. Results: The samples with antimicrobial agents from 5 manufacturers and the samples without antimicrobial agents from 2 manufacturers did not comply with the requirements of antimicrobial efficacy of Chinese Pharmacopoeia. A batch of sample from 1 manufacturers with ethyl p-hydroxybenzoate,a batch of sample from 1 manufacturers with acetone chloroform and 4 batches of samples from 1 manufactures with mercurothiolate failed on their content of antimicrobial agents. Freeze-thaw test indicated that the high concentration of ethyl p-hydroxybenzoate would result in the crystallization of lomefloxacin hydrochloride in the low temperature environment. Besides,we proved that the stability of acetone chloroform would be influenced by pH of solution and low density polyethylene packaging materials,and mercurothiolate would be absorbed by low density polyethylene packaging materials. Conclusion: Some problems existed in the usage of antimicrobial agents in lomefloxacin hydrochloride eye drops from some domestic manufacturers,and these manufacturers were advised to optimize the type and concentration of antimicrobial agents according to the requirements of Chinese Pharmacopoeia,and to optimize their formulation based on both biological tests and physical-chemical tests.