普通高血压药物缓释制剂用材料的制备技术与释药机理研究

发布时间：2018-04-22 13:27

本文选题：高血压 + 丝素蛋白　；参考：《重庆理工大学》2014年硕士论文

【摘要】：作为“富贵病”之一的高血压，是一种常见的心血管疾病，发病率呈逐年升高的趋势，对人体的心脏、脑、肾等重要器官造成损伤，严重威胁人类的健康。而高血压的治疗除了运动和食疗等非药物治疗外，只能依靠药物来治疗。而目前临床上对于高血压的治疗，仅能做到控制其发展，难以根治，这就决定了高血压患者一般需要长期服药。但长期服药会导致不良反应增多，副作用加强，因此对于高血压药物缓释制剂的研究越来越多。本课题在团队前期研究的基础上，巧妙的结合具缓释能力的纳米丝素蛋白和具备自组装能力的微米丝素蛋白，对高血压药物进行包裹、干燥、压片制备出载药缓释制剂用材料。对其的缓释能力、毒性及等进行了相关的研究。首先，分别制备出材料纳米丝素蛋白/聚乙烯醇/聚乙二醇（SFP/PVA/PEG）和SF/C2H5OH/(卡托普利)；然后，将二者依比例在一定的条件下结合制备出高血压药物缓释制剂用材料。对其进行宏观形貌、紫外光谱UV、红外光谱FTIR、扫描电镜SEM等表征研究，结果显示：药物缓释材料质量差异小、均一，成功制备出的药片具有潜在的缓释能力（具备较大的孔洞或缝隙）。衍生化分光光度法在409nm对卡托普利含量进行测定，其标准曲线呈现良好的相关性，并以此来研究其体外释药，结果显示：相比于市售的卡托普利片，自制的卡托普利片释放片在模拟胃、肠液中释放缓慢，均符合缓释制剂的动力学方程（Peppas释放动力学），适合开发为缓释制剂；释放后的药片具有均一孔洞，大小为1μm-10μm，推测其释放的机制应该是扩散或者扩散、溶蚀的共同作用。细胞毒性试验研究显示，细胞生长良好，缓释材料的浸提液及释放液等细胞毒性评级均为0级或1级，在安全范围内，未构成细胞毒性，符合生物材料细胞相容性要求；全身急性毒性、亚急性全身毒性研究发现，笼边观察、体重相对增长率、脏器系数、大体病理学检查等观察结果均无异常，，显示其无毒，符合医疗器械生物安全评价标准。研究结果表明，制备出的普通高血压药物缓释制剂用材料具备良好的缓释能力，且安全无毒，具有广阔的应用前景。
[Abstract]:As one of the "rich and noble diseases", hypertension is a common cardiovascular disease, the incidence of which is increasing year by year, which causes damage to human heart, brain, kidney and other important organs, and seriously threatens human health. The treatment of hypertension, in addition to exercise and diet therapy and other non-drug treatment, can only rely on drugs to treat. At present, the treatment of hypertension can only control its development, which is difficult to cure, which determines that patients with hypertension generally need long-term medication. But long-term medication will lead to more adverse reactions and side effects, so there are more and more studies on sustained release of hypertension drugs. On the basis of the team's previous research, the drug delivery materials for sustained-release preparation were prepared by combining nano-silk fibroin with sustained release and micron silk fibroin with self-assembly ability to encapsulate, dry, and press tablets. The slow release ability, toxicity and so on were studied. Firstly, nano-silk fibroin / polyvinyl alcohol / polyethylene glycol (SFP / PVA / PEG) and SFP / C2H / H / (captopril) were prepared, respectively. The macroscopic morphology, UV spectrum, FTIR, scanning electron microscopy (SEM) and so on were studied. The results showed that the quality difference of drug sustained-release materials was small and uniform. The successfully prepared tablets have potential slow-release capacity (large holes or gaps). The content of captopril was determined by derivatization spectrophotometry at 409nm. The standard curve of captopril showed a good correlation, and the drug release in vitro was studied. The results showed that compared with the captopril tablets sold on the market, The release of captopril tablets in the simulated stomach and intestinal fluid was slow, which was consistent with the kinetics equation of the sustained-release preparations and was suitable for development as a sustained-release preparation. The size is 1 渭 m ~ 10 渭 m, and the mechanism of its release should be diffusion, diffusion and dissolution. The cytotoxicity test showed that the cells grew well, and the cytotoxicity ratings of the extractions and release solutions of the slow-release materials were both grade 0 or grade 1, which did not constitute cytotoxicity within the safe range, and met the requirements of the cytocompatibility of the biomaterials. The study of systemic acute toxicity and subacute systemic toxicity found that the observation results of cage side observation, relative growth rate of body weight, organ coefficient and gross pathology were not abnormal, which showed that they were nontoxic and accord with the standard of biological safety evaluation of medical instruments. The results show that the prepared materials have good sustained-release ability, and are safe and non-toxic, and have a broad application prospect.
【学位授予单位】：重庆理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943;R96

【参考文献】