高乌甲素药物增溶性及缓释体系构建研究
发布时间：2018-10-08 16:59
【摘要】：本研究以提高高乌甲素(LA)水溶性并使其具有缓释效果,利用现代新药制剂技术中的药物包合技术和微球的载药技术来制备高乌甲素-p-环糊精聚合物(β-CDPH)包合物和高乌甲素-β-环糊精载药微球。同时分别对已经制备出的包合物和空白微球进行表征及性能的研究。并对制备出的聚合物包合物和载药微球分别进行载药量和包封率测定,对载药微球的制备工艺进行进一步的正交试验优化分析。最后模拟人体胃、肠及血液pH值环境对包合物和载药微球进行体外释放实验并为了了解制剂药物释放机理而进行了动力学方程拟合。实验结果为β-CDPH与LA能形成1：1摩尔比包合物,包合物中LA平均含量可达(27±1.1)%,且对LA增溶量可达11978mg/L,分别是LA-β-CD包合物增溶量的3.9倍、LA-β-CDPL包合物增溶量的1.5倍,高聚物包合物体外释放结果表明,在模拟血液的pH值环境中药物释放能够达到8小时。浸泡载药法制备载药微球的最佳工艺为反应中溶剂乙醇的浓度为70%,反应载药微球浸泡温度为45℃,微球与药物质量比为1：1,载药微球浸泡时间72h由此可得到载药率为(16.5±1.1)%的载药微球。载药微球体外释放实验表明,在模拟肠液pH值环境下药物的释放时间可长达20小时,并且其符合零级释放动力学曲线拟合方程和Ritger-Peppas方程。 本试验制备的新药制剂技术简单、易行,高聚物包合物能大大提高高乌甲素的水溶性,而且使高乌甲素包合物在模拟人体血液pH值环境下具有了一定的缓释效用。载药微球在模拟人体肠液pH值环境下能够使高乌甲素达到长效缓释的效果,从而能够方便患者的需要,显著减少给药次数。
[Abstract]:The aim of this study was to improve the water solubility of (LA) and to make it have slow release effect. In this paper, the new drug inclusion technology and the drug loading technique of microspheres were used to prepare the inclusion complexes of rapeconitin-p-cyclodextrin polymer (尾 -CDPH) and the drug loaded microspheres of aconitin-尾 -cyclodextrin. At the same time, the characterization and properties of the inclusion complexes and blank microspheres were studied. The drug loading and encapsulation efficiency of the polymer inclusion compound and the drug loaded microspheres were determined, and the preparation process of the drug loaded microspheres was optimized by orthogonal test. Finally, in order to understand the mechanism of drug release, the in vitro release experiments of inclusion compounds and drug loaded microspheres were carried out by simulating the pH values of human stomach, intestine and blood. The results show that 尾 -CDPH and LA can form 1:1 molar ratio inclusion complex, the average content of LA in inclusion complex can reach (27 卤1.1), and the solubilization amount of LA can reach 11978mg / L, which is 3.9 times that of LA- 尾 -CD inclusion complex and 1.5 times of that of LA- 尾 -CD inclusion complex. The release of polymer inclusion complexes in vitro showed that the drug release could reach 8 hours in simulated blood pH environment. The optimum conditions for the preparation of drug-loaded microspheres by soaking and loading are as follows: the concentration of solvent ethanol in the reaction is 70 and the soaking temperature of the drug loaded microspheres is 45 鈩，
本文编号：2257554
[Abstract]:The aim of this study was to improve the water solubility of (LA) and to make it have slow release effect. In this paper, the new drug inclusion technology and the drug loading technique of microspheres were used to prepare the inclusion complexes of rapeconitin-p-cyclodextrin polymer (尾 -CDPH) and the drug loaded microspheres of aconitin-尾 -cyclodextrin. At the same time, the characterization and properties of the inclusion complexes and blank microspheres were studied. The drug loading and encapsulation efficiency of the polymer inclusion compound and the drug loaded microspheres were determined, and the preparation process of the drug loaded microspheres was optimized by orthogonal test. Finally, in order to understand the mechanism of drug release, the in vitro release experiments of inclusion compounds and drug loaded microspheres were carried out by simulating the pH values of human stomach, intestine and blood. The results show that 尾 -CDPH and LA can form 1:1 molar ratio inclusion complex, the average content of LA in inclusion complex can reach (27 卤1.1), and the solubilization amount of LA can reach 11978mg / L, which is 3.9 times that of LA- 尾 -CD inclusion complex and 1.5 times of that of LA- 尾 -CD inclusion complex. The release of polymer inclusion complexes in vitro showed that the drug release could reach 8 hours in simulated blood pH environment. The optimum conditions for the preparation of drug-loaded microspheres by soaking and loading are as follows: the concentration of solvent ethanol in the reaction is 70 and the soaking temperature of the drug loaded microspheres is 45 鈩，
本文编号：2257554
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