论文部分内容阅读
背景:研究经皮穿刺瘤内注射蛋白变性剂并植入抗癌植入剂,使瘤体速毁、药物缓释持续杀灭残癌细胞的治癌新方法,但有关植入剂与变性剂能否联用尚不清楚。目的:观察氟尿嘧啶植入剂与蛋白变性剂 6 mol/L 盐酸的相容性,了解两者能否联用。设计、时间及地点:观察性实验,于2006-10/2007-03 在合肥工业大学完成。材料:Wistar大鼠78只,体质量(200±20)g,用于植入剂体内释放度测定;氟尿嘧啶植入剂(国药准字 H20030345,圆柱体颗粒,直径0.8mm,长 4.0mm,含氟尿嘧啶 2 mg/粒,批号:20060922),经检验符合氟尿嘧啶植入剂国家药品质量标准[WS1-(X-103)-2005Z],芜湖中人药业有限责任公司产品;体积分数为37%的盐酸为市售分析纯。方法:装有氟尿嘧啶植入剂和盐酸试管 96只,置(37.0±0.5) ℃下保温,于1,8,16,24,48,96,120,168,240,360,432,480,528,600,720,960h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的稳定性,紫外法测定药含量和饱和质量浓度;计算体外释放度,并与大鼠体内释放度比较。主要观察指标:氟尿嘧啶在变性剂中的近似溶解度、稳定性、形态变化;植入剂在变性剂和大鼠体内的释放度。结果:在(37.0±0.5) ℃盐酸中,氟尿嘧啶960 h内稳定,饱和质量浓度为(22.72±0.04)g/L,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;1,96,360,960h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:氟尿嘧啶植入剂在蛋白质变性剂6 mol/L盐酸中缓释药物,两者相容性好,可以联用。
BACKGROUND: To study the new method of treating cancer by injecting protein denaturant and implanting anticancer implants in percutaneous puncture tumor so as to destroy the tumor rapidly and drug sustained release. However, It is not yet clear whether we can work together. OBJECTIVE: To observe the compatibility of fluorouracil implants and protein denaturant 6 mol / L hydrochloric acid to understand whether they can be combined. DESIGN, TIME AND SETTING: Observational experiments were performed at Hefei University of Technology from October 2006 to March 2007. MATERIALS: A total of 78 Wistar rats, weighing 200 ± 20 g, were used to determine the in vivo release of the implants. Fluorouracil implants (Zhunzi H20030345, cylindrical particles, 0.8 mm in diameter, 4.0 mm in length, Fluorouracil 2 mg / tablet, batch number: 20060922), the product complies with the national drug quality standard for fluorouracil implant [WS1- (X-103) -2005Z], the product of Wuhu Zhongren Pharmaceutical Co., Ltd .; the volume fraction is 37% Hydrochloric acid is commercially available. Methods: Ninety-six tubes containing 5-fluorouracil and hydrochloric acid were incubated at 37.0 ± 0.5 ℃ for 6, 6, 6, 14, 48, 96, 120, 168, 240, 360, The stability of fluorouracil in hydrochloric acid was determined by high performance liquid chromatography and ultraviolet spectrophotometry. The drug content and saturation mass concentration were determined by ultraviolet method. The in vitro release was calculated and compared with that in rats. MAIN OUTCOME MEASURES: Approximate solubility, stability, morphological changes of fluorouracil in denaturant; Release of implant in denaturant and rat. Results: Fluorouracil was stable within 960 h at (37.0 ± 0.5) ℃, with a saturated mass concentration of (22.72 ± 0.04) g / L. The drug particles were intact and the surface was porous. (11.9 ± 5.3)%, (52.6 ± 4.3)%, (75.3 ± 3.8)% and (85.3 ± 2.1)%, respectively, at 1,96,360 and 960 hours. CONCLUSION: Fluorouracil implants release drug slowly in 6 mol / L HCl, a protein denaturant, which has good compatibility and can be used in combination.