摘要
目的研究硫酸皮肤素(DS)衍生物的抗血栓活性,筛选其口服制剂处方。方法以体外血栓形成法研究多硫酸化硫酸皮肤素(PSDS)和低分子多硫酸化硫酸皮肤素(LPSDS)的抗血栓作用,利用均匀设计优化方法确定最佳处方配比。结果scPS-DS和LPSDS在经第3和7小时各有1个峰值,而低分子硫酸皮肤素(LMWDS)则在第2和6小时各有1个峰值。po后PSDS和LPSDS在第3.5和8小时各有1个峰值,而LMWDS则在第3和7小时各有一个峰值。口服制剂辅料的最佳处方为LPSDS-牛磺胆酸盐-牛胆盐-油酸-卵磷脂,其配比为50∶0.79∶16.99∶7.05∶8.12。结论所制得的LPSDS和PSDS具有较好的抗血栓活性,筛选出了有效的LPSDS口服胶囊处方。
Abstract
OBJECTIVE To study antithrombotic activities of dermatan sulfate derivatives, and to optimize the formulation of their oral preparations. METHODS Thrombi produced by the Chandler loop method in vitro was used to study the antithrombotic function of poly-sulfated dermatan sulfate(PSDS)and low molecular weight poly-sulfated dermatan sulfate(LPSDS). The best oral formulation was selected by the optimization of the homogenious design methods. RESULTS After a subcutanous of administration of PSDS and LPSDS to rabbits, two peak-values of antithrombotic activity were obtained at 3 and 7 h,respectively, while the two peaks were obtained at 2 and 6 h after a subcutaneous administration of LMWDS. But two peak-values at 3.5 and 8 h were appeared after oral administrations of PSDS and LPSDS respectively, and at 3 and 7 h after an oral administration of LMWDS. The optimum oral formulation consisted of LPSDS, taurocholate, bovine bile salt, oleic acid, lecithin and their optimal proportion with the ratio of 50∶0.79∶16.99∶7.05∶8.12. CONCLUSION The LPSDS and PSDS obtained have higher antithrombotic activities. The oral formulation of LPSDS is optimized.
关键词
多硫酸化硫酸皮肤素 /
低分子多硫酸化硫酸皮肤素 /
抗血栓 /
口服制剂 /
处方筛选
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Key words
poly-sulfated dermatan sulfate /
low molecular weight poly-sulfated dermatan sulfate /
antithrombotic /
peroral dosage form /
formula bolting
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姬胜利;王潇;杜海燕.
硫酸皮肤素衍生物及其口服制剂抗血栓活性研究[J]. 中国药学杂志, 2006, 41(17): 1316-1319
JI Sheng-li;WNG Xio;DU Hi-yn.
Studies on Antithrombotic Activities of Dermatan Sulfate Derivatives and Their Preparations [J]. Chinese Pharmaceutical Journal, 2006, 41(17): 1316-1319
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参考文献
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脚注
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基金
山东省自然科学基金资助项目(Y2000C22)
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