摘要
目的①建立RGD-Hirudin微球制备工艺;②建立缓释微球制剂中药物活性、含量的测定方法;③分析微球制备工艺中的各个关键参数对微球质量的各个指标的影响情况.方法选择聚乙烯醇（PVA）作为助乳剂,聚乳酸聚羟基乙酸（PLGA）作为微球的生物可降解载体,二氯甲烷作为有机溶剂,溶剂蒸发温度为室温,运用溶剂挥发法制备W/O/W的双乳微球制剂.在微球的制备工艺研究中,考察内水相中水油比例对微球粒径以及收率的影响,助乳剂PVA浓度对微球外观以及微球的包封率和收率的影响,超声次数对微球成球率以及药物活性的影响,挥发搅拌速度对微球的成球率以及外观的影响,不同黏度的PLGA对微球的外观以及分散度的影响,NaCl浓度对微球的包封率、收率以及载药量的影响等.结果利用颗粒粒径系统（PSS）对所制备微球样品的分析得出,微球平均粒径81.38μm,适合作进一步体内研究.几批微球的载药量和收率都很高,分别为83.92%～96.3%和79.93%～95.05%;包封率为23.95%～65.13%.其中NaCl浓度、PVA浓度对微球包封率的影响比较明显.结论微球的稳定性实验表明,微球释放率稳定,并且释放的重组双功能水蛭素（RGD-Hirudin）活性稳定性保持良好,体外释放实验得出其具有缓慢释放的效果,为进一步做动物体内实验打下了基础.
Purpose The main purposes of our research were to： 1. set up the method of the RGDHirudin microsphere preparation; 2. set up the method to test the activity and the content of the medicine contained in the microsphere; 3. analyse the key factors on the quality of the microsphere preparation. Methods Co-poly lactic acid glycolic acid （PLGA） microsphere was prepared by a modified solvent evaporation method by a double emulsion with the use of polyvinylalcohol （PVA） as emulsification; PLGA was used as biodegradable material and dichloromethane as organic solvent. The influence of formulation factors including the W1/O on microsphere diameter distribution and yield coefficient;PVA concentration on microsphere appearance, encapsulation and yield coefficient; ultrasound on spherulization average and medicine activity; stirring speed on spherulization average and microsphere appearance; PLGA on microsphere appearance and microsphere dispersity; concentration of NaCl on encapsulation efficiency, yield coefficient and medicine content etc were studied. Results The size of all the fabricated microsphere was measured according to the several factors that affect the particle size. The average diameter was 81.38 μm, which is good for further research. The medicine content and the percent yield of all the microsphere was high, which ranged from 83. 92% - 96. 3% and 79.93% - 95.05% respectively. The encapsulation efficiency was about 23.95% - 65. 13%. We found that the concentration of the NaCl and PVA were the very important factors to the encapsulation efficiency. Physiological activity of RGD-Hirudin containing in the microsphere and the release rate of the microsphere were controlled. Furthermore, the release rate was stable. Conclusions The physiologic activity of RGD-Hirudin released from the microspheres was stable. PLGA-RGD-Hirudin microspheres were controlled released by the in vitro studies. Therefore, the in vivo experiment was well grounded.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2006年第1期17-23,共7页
Fudan University Journal of Medical Sciences
关键词
重组双功能水蛭素
生物可降解材料
溶剂挥发法
包封率
控释制剂
微球
RGD-Hirudin
biogradable material
solvent evaporation method
encapsulation efficiency
controlled released preparation
microsphere
