阿司匹林肠溶缓释片的研究
发布时间：2018-10-29 15:49
【摘要】：目的：阿司匹林（Aspirin）是一种应用历史悠久的非甾体抗炎药，近几年来更是成为血栓栓塞性疾病治疗的首选药物。当人体血液中血小板被活化时，细胞内钙离子浓度升高，促使细胞膜磷脂释放出花生四烯酸，花生四烯酸在环氧化酶作用下分别转化成血栓素A2和前列环素，而阿司匹林通过使环氧化酶乙酰化失活来减少血栓素A2的生成，进而抑制血小板聚集，达到减少血管堵塞的发生率，有效地预防血栓形成的目的，常用于冠状动脉血管栓塞导致的心肌梗塞（AMI）及心绞痛；脑血管栓塞导致的脑血栓中风；肺动脉栓塞导致的肺梗塞、肺源性心脏病；肢体动脉栓塞导致的肢端疼痛或坏死，肢体静脉栓塞导致的局部水肿和疼痛等。但长期大量服用阿司匹林易造成胃肠道不良反应，如胃溃疡，胃肠穿孔甚至胃出血。现需要改变其剂型进而减少其不良反应的发生，延长药物半衰期，缓慢释药，使其血药浓度在较长时间内不会出现大的波动，改善药效，更好的提高生物利用度。本文对阿司匹林肠溶缓释片的制备工艺及质量标准进行了考察。方法：本文通过释放度检测试验对阿司匹林肠溶缓释片的处方进行了初步筛选，并运用均匀设计法对处方进行了优化；将处方量扩大100倍进行中试实验，验证了处方的可行性及合理性。对阿司匹林肠溶缓释片的质量标准进行考察，采用紫外-可见分光光度计法对其释放度进行测定，并采用高效液相色谱法进行了方法学考察。最后，对阿司匹林肠溶缓释片进行了稳定性考察，包括高温、高湿条件下的影响因素考察，为期六个月的加速实验以及十二个月的长期实验，考察其外观、释放度及含量的变化。结果：筛选出的最佳处方为：阿司匹林25g，淀粉9g，十二烷基硫酸钠0.75g，微晶纤维素2g，羟丙基甲基纤维素(K15M)5.25g，滑石粉1g，3%聚乙烯吡咯烷酮醇溶液适量。经过中试实验结果考察，该处方符合国家标准。阿司匹林肠溶缓释片质量标准的考察结果，确认该制备工艺可行、重现性良好。稳定性考察实验结果良好，各项指标均未见明显变化，表明该工艺制备的阿司匹林肠溶缓释片的质量稳定。结论：该论文对处方辅料配比及制备工艺进行优化，得到体外释放度较好的阿司匹林肠溶缓释片，从而在减少胃肠道不良反应的同时提高其生物利用度，，同时减少服药次数，使药物缓慢释放，达到一个稳态的血药浓度，提高阿司匹林肠溶缓释片的临床应用效果，提高了患者的依从性。
[Abstract]:Objective: aspirin (Aspirin) is a non-steroidal anti-inflammatory drug which has a long history and has become the first choice in the treatment of thromboembolic diseases in recent years. When platelets in human blood were activated, the intracellular calcium concentration increased, which resulted in the release of arachidonic acid from cell membrane phospholipid and the conversion of arachidonic acid to thromboxane A2 and prostacyclin under the action of cyclooxygenase, respectively. Aspirin reduces thromboxane A 2 production by deactivating cyclooxygenase, thereby inhibiting platelet aggregation, reducing the incidence of vascular blockage and effectively preventing thrombosis. It is often used in (AMI) and angina pectoris caused by coronary artery embolism. Cerebral thrombus stroke caused by cerebral vascular embolism, pulmonary infarction caused by pulmonary embolism, pulmonary heart disease, pain or necrosis of extremity caused by arterial embolism, local edema and pain caused by venous embolism of extremities, etc. But long-term use of aspirin is prone to gastrointestinal adverse reactions, such as gastric ulcers, gastrointestinal perforation and even gastric bleeding. At present, it is necessary to change the dosage form and reduce the occurrence of adverse reactions, prolong the half life of the drug, release the drug slowly, make the blood drug concentration not fluctuate in a long time, improve the efficacy and improve the bioavailability. The preparation process and quality standard of aspirin enteric sustained-release tablets were investigated. Methods: the formulation of aspirin enteric sustained-release tablets was preliminarily screened by release test, and the formulation was optimized by uniform design method. The feasibility and rationality of the prescription were verified by expanding the prescription volume by 100 times. The quality standard of aspirin enteric-soluble sustained-release tablets was investigated and its release was determined by UV-Vis spectrophotometer and HPLC. Finally, the stability of aspirin enteric sustained-release tablets was investigated, including the influence factors under high temperature and high humidity, the accelerated test for six months and the long-term experiment for 12 months. The change of release degree and content. Results: the best prescription was aspirin 25g, starch 9g, sodium dodecyl sulfate 0.75g, microcrystalline cellulose 2g, hydroxypropyl methyl cellulose (K15M) 5.25g, talc powder 1g / 3% polyvinylpyrrolidone alcohol solution. The result of the pilot experiment shows that the prescription meets the national standard. The quality standard of aspirin enteric sustained-release tablets was investigated and the preparation process was confirmed to be feasible and reproducible. The results of stability test showed that the quality of aspirin enteric-soluble sustained-release tablets was stable. Conclusion: in this paper, the formulation and preparation of excipients were optimized to obtain aspirin enteric-soluble sustained-release tablets with good release rate in vitro, so as to reduce the adverse reactions of gastrointestinal tract and increase the bioavailability while reducing the times of taking drugs. The drug was released slowly to a steady blood concentration, and the clinical application effect of aspirin enteric sustained-release tablets was improved, and the compliance of the patients was improved.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R943
本文编号：2298126
[Abstract]:Objective: aspirin (Aspirin) is a non-steroidal anti-inflammatory drug which has a long history and has become the first choice in the treatment of thromboembolic diseases in recent years. When platelets in human blood were activated, the intracellular calcium concentration increased, which resulted in the release of arachidonic acid from cell membrane phospholipid and the conversion of arachidonic acid to thromboxane A2 and prostacyclin under the action of cyclooxygenase, respectively. Aspirin reduces thromboxane A 2 production by deactivating cyclooxygenase, thereby inhibiting platelet aggregation, reducing the incidence of vascular blockage and effectively preventing thrombosis. It is often used in (AMI) and angina pectoris caused by coronary artery embolism. Cerebral thrombus stroke caused by cerebral vascular embolism, pulmonary infarction caused by pulmonary embolism, pulmonary heart disease, pain or necrosis of extremity caused by arterial embolism, local edema and pain caused by venous embolism of extremities, etc. But long-term use of aspirin is prone to gastrointestinal adverse reactions, such as gastric ulcers, gastrointestinal perforation and even gastric bleeding. At present, it is necessary to change the dosage form and reduce the occurrence of adverse reactions, prolong the half life of the drug, release the drug slowly, make the blood drug concentration not fluctuate in a long time, improve the efficacy and improve the bioavailability. The preparation process and quality standard of aspirin enteric sustained-release tablets were investigated. Methods: the formulation of aspirin enteric sustained-release tablets was preliminarily screened by release test, and the formulation was optimized by uniform design method. The feasibility and rationality of the prescription were verified by expanding the prescription volume by 100 times. The quality standard of aspirin enteric-soluble sustained-release tablets was investigated and its release was determined by UV-Vis spectrophotometer and HPLC. Finally, the stability of aspirin enteric sustained-release tablets was investigated, including the influence factors under high temperature and high humidity, the accelerated test for six months and the long-term experiment for 12 months. The change of release degree and content. Results: the best prescription was aspirin 25g, starch 9g, sodium dodecyl sulfate 0.75g, microcrystalline cellulose 2g, hydroxypropyl methyl cellulose (K15M) 5.25g, talc powder 1g / 3% polyvinylpyrrolidone alcohol solution. The result of the pilot experiment shows that the prescription meets the national standard. The quality standard of aspirin enteric sustained-release tablets was investigated and the preparation process was confirmed to be feasible and reproducible. The results of stability test showed that the quality of aspirin enteric-soluble sustained-release tablets was stable. Conclusion: in this paper, the formulation and preparation of excipients were optimized to obtain aspirin enteric-soluble sustained-release tablets with good release rate in vitro, so as to reduce the adverse reactions of gastrointestinal tract and increase the bioavailability while reducing the times of taking drugs. The drug was released slowly to a steady blood concentration, and the clinical application effect of aspirin enteric sustained-release tablets was improved, and the compliance of the patients was improved.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R943
【参考文献】
相关期刊论文 前1条
1 王英俊;赵贝贝;;阿司匹林的作用及其机制研究进展[J];现代农业科技;2009年18期
本文编号：2298126
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