首页> 中文期刊> 《山东医药》 >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

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

         

摘要

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 , pH value and osmotic pressure was evaluated .The stability of 5-Fu in the 5-Fu and TPN solution was deter-mined by HPLC.The H22 transplanted models of mice were established .Sixty mice were divided into six groups:5-FU-TPN-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 con-trol 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 2 after the last administration , mice were killed and antitumor rate was calculated .Results Compared with the blank paren-teral nutrition solution, there were no significant changes in the appearances , MD, CV, pH 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-FU-TPN-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/mL is better than single administration of 5-Fu.%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、pH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、pH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。

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