氟尿嘧啶植入剂在蛋白变性剂盐酸中的释药行为(英文)  

Drug-release effect of fluorouracil implants in protein denaturant hydrochloric acid

作　　者：王世亮[1,2] 王竞[3] 尹情胜[2] 任翠丽[2] 马晓芹[2] 冯梅[4] 

机构地区：[1]安徽职业技术学院,安徽省合肥市230051 [2]合肥工业大学控释药物研究室,安徽省合肥市230009 [3]四川大学华西药学院,四川省成都市640041 [4]北京富地古医药研究所,北京市100078

出　　处：《中国组织工程研究与临床康复》2009年第12期2395-2400,共6页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：Supported by: the National Natural Science Basic Research Foundation of China, No. [2001]51;the Tenth Five-Year Plan Science and Technology Research Plan of Anhui Province, No. 01013036~~

摘　　要：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： Directly percutaneous injection of protein-denaturant hydrochloric acid （PDHA） into tumors can lead to fast killing of tumor, sustained drug release and prevention of in situ recurrence of tumor. However, whether implants can be used combined with denaturant still remains unknown. OBJECTIVE： To investigate the compatibility of fluorouracil implants and PDHA （6 mol/L）. DESIGN, TIME AND SETTING： Observational study was performed in the Hefei Industry University between October 2006 and March 2007. MATERIALS： A total of 78 Wistar rats, weighing （200±20） g, half males and half females, were used for testing drug release in vivo. Drugs fluorouracil implants （H20030345; columniform particle, diameter 0.8 mm, length 4 ram; specifications： Fluorouracil 2 mg/particle; batch number： 20060922; meeting the National Drug Quality Standards [WSl-（X-103）-2005Z]） were provided by Wuhu Zhongren Pharmaceutical Company,Ltd. Hydrochloric acid （37%） was analytical reagent. METHODS： 96 tubes of the implants and PDHA were kept at （37.0± 0.5） %. Each time, six samples were collected at 1, 8, 16, 24 96, 120, 168, 240, 360, 432,480, 528, 600, 720, and 960 hours after incubation. Appearance of the implants was observed by microscope. Stability of quorouracil in PDHA was determined by HPLC and ultraviolet absorb method. Based on the entering quantity and residual quantity of fluorouracil, the release rates were calculated. MAIN OUTCOME MEASURES： The approximate solubility, stability and morphological change of fluorouracil in denaturant and the corresponding drug release character in both denaturant and rats in rive. RESULTS： At （37.0±0.5） ℃, the fluorouracil was stable for 960 hours in PDHA, the saturated concentration of fluorouracil was （22.72 ±0.04） g/L. The appearance of implants was intact. The surface was porous. Compared with the speed of releasing drug in rats, the speed of releasing drug was faster in the early stage of release process and slower in the later s

关 键 词：氟尿嘧啶 植入剂 变性剂 盐酸 缓释 化疗 

分 类 号：R318[医药卫生—生物医学工程]