5-氟尿嘧啶与肠外营养液配伍制剂的体外稳定性和体内抗肿瘤活性  

Stability in vitro and antitumor activity in vivo of preparations of 5-Fu mixed with parenteral nutrition solution

作　　者：刘广宣[1] 赵茜[1] 隋月[1] 关丁越[1] 孙博[1] 朱丹彤[1] 齐先福[1] 

机构地区：[1]辽宁省肿瘤医院,沈阳110042

出　　处：《山东医药》2016年第44期8-11,共4页Shandong Medical Journal

基　　金：辽宁省自然科学基金资助项目(2103020186)

摘　　要：目的观察5-氟尿嘧啶(5-Fu)与肠外营养液配伍制剂(简称5-Fu肠外营养液)的体外稳定性和体内抗肿瘤活性,为其临床应用提供依据。方法配制空白肠外营养液及5-Fu肠外营养液,室温条件下观察配制24 h内两种营养液的外观、脂肪乳微粒的平均粒径及变异系数、p H值、渗透压,采用高效液相色谱分析法分析5-Fu肠外营养液中5-Fu含量的稳定性。将小鼠肝癌细胞H22瘤株接种于小鼠,制备移植性实体瘤模型。接种第3天将小鼠随机分为5-FU-TPN-L、5-FU-TPN-M、5-FU-TPN-H、5-FU-NS、TPN及对照组,每组10只。前三组分别腹腔注射含30、65、130 mg/kg 5-Fu的5-Fu肠外营养液,后三组分别腹腔注射含65 mg/kg 5-Fu的生理盐水注射液及等量的空白肠外营养液、生理盐水,均隔天给药1次,共给药5次。末次给药结束第2天处死小鼠,计算抑瘤率。结果 5-Fu肠外营养液与空白肠外营养液配制24 h内外观、脂肪乳微粒的平均粒径及变异系数、p H值、渗透压和含量均无明显变化(P均>0.05)。5-FU-TPN-L、5-FU-TPN-M、5-FU-NS、TPN组抑瘤率分别为24.3%、91.8%、78.7%、14.6%,5-FU-TPN-M、5-FU-NS组抑瘤率均高于5-FU-TPN-L、TPN组,且5-FU-TPN-M组高于5-FU-NS组,组间比较P均<0.01;5-FU-TPN-H组药物毒性较大,给药过程中死亡6只,未统计抑瘤率。结论 5-Fu肠外营养液配制24 h内性质稳定,抗肿瘤活性较单独给予5-Fu提高。Objective To observe the compatible stability in vitro and antitumor activity in vivo of preparations of 5-fluorouracil（ 5-Fu） mixed with total parenteral nutrition（ TPN） solution（ 5-Fu and TPN solution） and to provide the basis for its clinical application. Methods The blank parenteral nutrition solution and 5-Fu and TPN solution were mixed at room temperature for 24 h. The appearances were observed and the mean diameter（ MD） and coefficient of variation（ CV）of fat particles,p H value and osmotic pressure was evaluated. The stability of 5-Fu in the 5-Fu and TPN solution was determined by HPLC. The H22 transplanted models of mice were established. Sixty mice were divided into six groups： 5-FUTPN-L（ 30 mg/kg）,5-FU-TPN-M（ 65 mg/kg）,5-FU-TPN-H（ 130 mg/kg）,5-FU-NS（ 65 mg/kg）,TPN and the control group,each group had 10 mice. On the day 3 after being inoculated with H22 tumor cells,the mice in the six groups were intraperitoneally injected with the above six kinds of liquids,separately,once every other day for 5 times. On day 2after the last administration,mice were killed and antitumor rate was calculated. Results Compared with the blank parenteral nutrition solution,there were no significant changes in the appearances,MD,CV,p H value,osmotic pressure and the contents of 5-Fu within 24 h of 5-Fu and TPN solution（ all P〉0. 05）. The antitumor rates of the 5-FU-TPN-L,5-FUTPN-M,5-FU-NS,and TPN groups were 24. 3%,91. 8%,78. 7% and 14. 6%,the antitumor rate of the 5-FU-TPN-M and 5-FU-NS groups were higher than those of the 5-FU-TPN-L and TPN groups,and the antitumor rate of 5-FU-TPN-M group was higher than that of the 5-FU-NS group,significant difference was found between every two groups（ all P〈0. 01）. The toxicity of 5-FU-TPN-H was strong,and 6 mice died,so no statistics were carried out. Conclusion 5-Fu in TPN solution is stable within 24 h and the antitumor effect of 5-Fu at 65 mg/m L is better than single administration of 5-Fu.

关 键 词：5-氟尿嘧啶 肠外营养液 配伍 抑瘤率 小鼠 

分 类 号：R979.1[医药卫生—药品]