注射用头孢唑林钠与脂肪乳的配伍稳定性及对体内外抑菌活性的影响

Stability of cefazolin sodium for injection compatible with fat emulsion and effects on its in vitro and in vivo antifungal activity

目的考察注射用头孢唑林钠(CS)与脂肪乳配伍时的稳定性及配伍后在体内外的抑菌活性。方法分别利用pH计和动态光散射粒径仪检测CS与脂肪乳配伍液在25℃和4℃下24 h内的pH值和粒径的变化情况,采用HPLC法检测配伍液中药物的含量变化情况,采用微量液体稀释法考察配伍液的体外抑菌活性,考察CS(900、300、100 mg·kg^(-1))分别与生理盐水及10%脂肪乳配伍后对金黄色葡萄球菌感染小鼠存活率的影响。结果 CS分别与10%、20%和30%脂肪乳配伍后,脂肪乳的外观、pH值、粒径、含量均无明显改变(P>0.05)。CS-10%脂肪乳、CS-20%脂肪乳和CS-30%脂肪乳对大肠杆菌的最低抑菌浓度分别为1、0.5、0.5 mg·L^(-1),与CS(2 mg·L^(-1))相比无显著差异(P>0.05);对金黄色葡萄球菌的最低抑菌浓度分别为0.25、0.25、0.25 mg·L^(-1),与CS(0.5 mg·L^(-1))相比无显著差异(P>0.05)。CS 300 mg·kg^(-1)与10%脂肪乳配伍后对金黄色葡萄球菌的体内抑菌作用(小鼠7 d存活率40%)优于用生理盐水稀释(小鼠7 d存活率20%)(P<0.01)。结论 CS在分别与10%、20%和30%脂肪乳配伍时稳定性良好,与10%脂肪乳配伍对体内外抑菌效果也无影响。

AIM To study the stability injection （CS） when it respectively combined and in vitro and in with lipid emulsion. vivo antifungal activity METHODS The pH of cefazolin sodium for value and particle size changes of compatible solution within 24 h at 25 ℃ and 4 ℃ were measured by pH meter and Zetasizer Nano ZS system. The contents of CS in the compatible solution were determined by high performance liquid chromatograph （HPLC） in 0 to 24 hours. The in vitro antifungal activity of compatible solution were investigated by microdilution. The effect of CS 900, 300 and 100 mg .kg-1 combined with 10% lipid emulsion or saline on survival rates of mice infected with Staphylococcus aureus were investigated in vivo. RESULTS When CS combined with 10%, 20% and 30% lipid emulsion, there were no significant changes in absorption peak, absorbance, color, pH value and particle sizes of the compatible solution （P 〉 0.05）. The minimum inhibitory concentrations of CS combined with 10%, 20%, 30% lipid emulsion were 1, 0.5, 0.5 mg.L-1 to Bacillus coli, respectively, with no significant difference compared with that of CS （2 mg.L-1） （P 〉 0.05）. The minimum inhibitory concentrations of CS combined with 10%, 20%, 30% lipid emulsion were 0.25, 0.25, 0.25 mg.L-1 to Staphylococcus aureus, respectively, with no significant difference compared with that of CS （0.5 mg.L-1） （P 〉 0.05）. The 7-day survival rate of CS 300 mg.kg-1 combined with 10% lipid emulsion or saline were 40% and 20%, respectively, so the inhibitory effect of CS 300 mg.kg-1 combined with 10% lipid emulsion was better than when it diluted with saline in vivo （P 〈 0.01）. CONCLUSION The compatible solution of CS combined with 10%, 20% and 30% fat emulsion have good stability and there is no effect on the in vitro and in vivo antifungal activity when CS combined with 10% fat emulsion.