氟尿嘧啶植入剂在蛋白变性剂盐酸中行为研究

Study on Behavior of Fluorouracil Implants in Protein Denaturant Hydrochloric Acid

目的研究氟尿嘧啶植入剂与蛋白变性剂6 mol·L^(-1)盐酸的相容性,了解两者能否联用。方法装有氟尿嘧啶植入剂和盐酸试管96只置(37±0.5)℃下保温,于不同时间点各取6只试管内药粒,显微镜观察形态;高效液相色谱和紫外法测定氟尿嘧啶在盐酸中稳定性,紫外法测定药含量和饱和浓度;计算体外释放度,并与大鼠体内释放度比较。结果在(37±0.5)℃盐酸中,氟尿嘧啶960 h稳定,饱和质量浓度为(22.72±0.04)g·L^(-1),植入剂药粒完整,表面多孔,释药速率与大鼠体内相比,前期大,后期小,药物难以放完;1,96,360,960 h时释放度分别为(11.9±5.3)%,(52.6±4.3)%,(75.3±3.8)%,(85.3±2.1)%。结论氟尿嘧啶在(37±0.5)℃盐酸中略溶,960 h稳定,氟尿嘧啶植入剂在蛋白质变性剂6 mol·L^(-1)盐酸中缓释药物,两者相容性好,可以联用。

OBJECTIVE To investigate the compatibility of fluorouracil implants and protein-denaturant hydrochloric acid （PDHA）. METHODS 96 Tubes of the implants and PDHA were kept at the （37 ± 0. 5 ）℃. Six samples were collected at 1,25,49, 73,97,121 h after incubation. Appearance of the implants was observed by microscope. Stability of fluorouraeil in PDHA was determined by HPLC and uhraviolet absorb method, quantity of fluorouracil in the implants and saturated concentration of fluorouracil in PDHA were determined b） ultraviolet absorb method. According to entering quantity and residual quantity of fluorouracil, the release degrees were calculated. RESULTS At （37 ± 0. 5） ℃, the fluorouracil was stable for 960 h in PDHA, the saturated concentration of fluorouracil was （22.72 ± 0. 04 ） g·L^-1. The appearance of implants was completed. Many bores at surface. Compared with the speed of release drug in rats, the speed of release drug was faster in the first half of release process and slower in the last half of release process. The drug was released incompletely. During the period of 1,96,360 and 960 h, the implants release degrees were （11.9 ± 5.3 ） %, （52 ± 4.3 ） %, （ 75.3 ± 3.8 ） % and （ 85.3 ± 2.1 ） % , respectively. CONCLUSION The fluorouracil is stable in PDHA 960 h at （37 ± 0. 5） ℃. The fluorouracil implants and 6 mol·L^-1 hydrochloric acid arc compatible and no influence was detected during the observation.