口服茯苓多糖硫酸酯前体脂质体的制备及其抗凝血活性研究

Preparation of Oral Pachyman Sulfate Proliposome and Its Anticoagulant Activity

茯苓多糖硫酸酯（Pachyman Sulfate,PS）具有和肝素相似的抗凝血活性和机制,研制PS口服制剂意义显著.以氯磺酸-吡啶法制备PS,以海藻糖为载体、薄膜蒸发法制备PS前体脂质体口服制剂,并初步研究其抗凝血活性.PS得率97％,硫酸根取代度3,重均分子量9 978 Da;PS前体脂质体为乳白色粉末,重建脂质体为球状或近球状小囊泡,形态完整,粒径较均匀,有效粒径分布范围在0.7～1.4 μm之间,多分散指数小于0.4,zeta电位小于-25 mV,分散性好.重建载药脂质体包封率为20.3％,大鼠口服重建载药脂质体后凝血时间延长率达46％,且有统计学意义.重建空白脂质体有助于PS的口服吸收,且脂质体包封PS后吸收效果更好.

The isolated pachyman from Poria cocos was reacted with chlorosulfonic acid to obtain pachyman sulfate （PS）. PS has similar anticoagulant, antithromhotic activities and mechanism in comparision with heparin. The oral PS proliposome was made by thin film evaporation with trehalose as carrier. The anticoagulant activity of the PS proliposome was studied in vivo. The yield rate of PS was 97% ; the degree of sulfation （DS） of PS was 3 ; the PS average molecular weight was 9 978 Da. The PS proliposome was milk white powder, and the reconstructed liposome was spherical or nearly spherical vesicle with complete surface. The particle size distribution was in the range of 0.7 - 1.4 μm with the polydispersity index less than 0.4 ; the zeta potential of particles was less than -25 inV. These indica- ted the product a good dispersion. The PS encapsulation efficiency of reconstructed liposome was 20. 3%. The rate of prolonging blood clotting time was 46% after oral administration of PS reconstructed liposome in rats. The reconstructed blank liposome was conductive to the oral absorption of PS, but the PS encapsulated in liposome was more easily absorbed.