双氯芬酸钠滴眼液抑菌剂剂量筛选及抑菌效力考察

Studies on Antimicrobial Preservatives Screening and Antimicrobial Efficacy of Diclofenac Sodium Eye Drops

目的研究双氯芬酸納滴眼液的抑菌效力,探索抑菌剂的合理添加量。方法按《中国药典》2015年版四部,以大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、白色念珠菌和黑曲霉为实验菌株,测定10家企业双氯芬酸钠滴眼液的抑菌效力,并对硫柳汞、羟苯乙酯和苯扎氯铵3种抑菌剂的最低有效量进行研究。结果10家企业中没有一家抑菌效力达到A级,有3家企业:达到B级,另外7家均未达到B级。抑菌剂剂量筛选实验中,当双氯芬酸钠滴眼液含硫柳汞质量农度达到0.01 mg·mL^-1,羟苯乙酯质量浪浓度达到0.3 mg·mL^-1时,抑菌效力可达到B级,苯扎氯铵质量农浓度达到0.01 mg·mL^-1时,抑菌效力即可达到A级。结论市售双氯芬酸钠滴眼液的抑菌效力不容乐观,建议企业合理添加抑菌剂,对抑菌剂的理化指标和生物指标一同评价保证药品质量安全可靠。

OBJECTIVE To evaluate the bacteriostatic efficacy of diclofenac sodium eye drops and to explore the reasonable dose of benzalkonium chloride,ethylparaben and thimerosal in diclofenac sodium eye drops.METHODS According to the method of bac-teriostatis effect test in 2015 edition of Chinese Pharmacopoeia(Ch.P),and Escherichia coli,Staphylococcus aureus,Pesudomonas aeruginosa,Candida albicans and Aspergillus niger as test strains,the bacteriostatis effect of diclofenac sodium eye drops from 10 batches of the samples was determined.Also,the concentration gradient of benzalkonium chloride,ethylparaben and thimerosal in diclofenac sodium eye drops was designed to investigate the optimum bacteriostatic concentration.RESULTS The samples from 3 manufacturers could reach level B,no sample could reach level A,and those from 7 manufacturers did not comply with the specification.When the concentration of thimerosal was 0.01 mg·mL^-1 and the concentration of ethylparaben was 0.3 mg·mL^-1 in diclofenac sodium eye drops,the bacteriostatic efficacy could reach level B.When the concentration of benzalkonium chloride was 0.01 mg·mL^-1,the bacteriostatic efficacy could reach level A.CONCLUSION The bacteriostatis effect of diclofenac sodium eye drops from 10 batches of the samples is not good,It is recommended that these manufacturers should optimize the type and concentration of antimicrobial agents and optimize their formulation based on both biological tests and physical-chemical tests to ensure drug safety.