盐酸表柔比星联合维生素K_(2)的药效学考察  

Investigation on anti-tumor efficacy of epirubicin hydrochloride combined with vitamin K_(2)

作　　者：张艳晶 杨牧 胡雅维 刘越男[1] 张春蕾 ZHANG Yanjing;YANG Mu;HU Yawei;LIU Yuenan;ZHANG Chunlei(Department of Pharmacy,the Fourth People’s Hospital of Shenyang,Shenyang 110000,China;Liaoning Ispectioin Examination&Certification Center,Shenyang 110030,China;Department of Pharmacy,Erdos Central Hospital,Inner Mongolia Erdos,Shenyang 017000,China)

机构地区：[1]沈阳市第四人民医院药剂科,辽宁沈阳110000 [2]辽宁省检验检测认证中心,辽宁沈阳110030 [3]鄂尔多斯市中心医院药剂科,内蒙古鄂尔多斯017000

出　　处：《沈阳药科大学学报》2021年第1期65-73,共9页Journal of Shenyang Pharmaceutical University

摘　　要：目的考察不同剂量盐酸表柔比星(epirubicin hydrochloride,EPI)脂质体联合维生素K_(2)(Vitamin K_(2),VK_(2))纳米乳的抗肿瘤效果。方法制备唾液酸(sialic acid,SA)修饰的EPI脂质体(EPISAL)、维生素K_(2)纳米乳(VK_(2)-E)、SA修饰的维生素K_(2)纳米乳(VK_(2)-SAE),并对制剂进行了表征和稳定性及药动学考察。使用S180肉瘤为模型,采用多个参数综合评价VK_(2)-E、VK_(2)-SAE分别联合不同剂量EPI-SAL的体内抗肿瘤效果。结果剂量分别为0.75、1.5、3.0 mg·kg^(-1)EPI-SAL,5 mg·kg^(-1)VK_(2)-E和5 mg·kg^(-1)VK_(2)-SAE的单独使用均具有一定的抗肿瘤作用;当不同剂量的EPI-SAL与VK_(2)-E、VK_(2)-SAE联合治疗后,效果均优于EPI-SAL的单独治疗;其中EPI-SAL与VK_(2)-SAE的联合治疗效果优于EPI-SAL联合VK_(2)-E;值得注意的是,低剂量的EPI-SAL与VK_(2)-SAE联用后,体内抗肿瘤效果与单独使用高剂量EPI-SAL的治疗效果相当。结论VK_(2)可以协同EPI发挥抗肿瘤作用,进而减少EPI的使用剂量,可降低EPI剂量过大带来的心脏毒性等副作用。Objective To evaluate the anti-tumor activity of different doses of epirubicin hydrochloride(EPI)liposome combined with vitamin K_(2)(VK_(2))nanoemulsion.Methods EPI liposome(EPI-SAL)modified by sialic acid(SA),VK_(2) nanoemulsion(VK_(2)-E)and SA-modified VK_(2) nanoemulsion(VK_(2)-SAE)were prepared.At the same time,the stability and pharmacokinetics of various preparation were characterized and investigated.Results EPI-SAL with the dose of 0.75,1.5,3.0 mg·kg-1,VK_(2)-E with the dose of 5 mg·kg^(-1) and 5 mg·kg^(-1) VK_(2)-SAE alone had certain anti-tumor effects.When different doses of EPI-SAL were combined with VK_(2)-E and VK_(2)-SAE,the effect was better than that of EPI-SAL alone.The combination of EPI-SAL and VK_(2)-SAE was better than EPI-SAL combined with VK_(2)-E.It was worth noting that the low-dose EPI-SAL combined with VK_(2)-SAE had an anti-tumor effect comparable to that of highdose EPI-SAL alone.Conclusion VK_(2) can synergize with EPI to exert anti-tumor effect,thereby reducing the dose of EPI,and reducing side effects such as cardiotoxicity caused by excessive dose of EPI.

关 键 词：盐酸表柔比星 维生素K_(2) 唾液酸 脂质体 纳米乳 抗肿瘤 

分 类 号：R96[医药卫生—药理学]