水蛭素的给药途径及其相关剂型研究进展

作为一种抗凝防栓良药，水蛭素（hirudin）特别是重组水蛭素的研究日益深入。针对水蛭素存在的一些缺陷，如半衰期短、临床应用时还存在一定的出血危险、预防动脉血栓的效果并不理想等，一些新的水蛭素衍生物、重组水蛭素模拟肽都在研发中，同时对水蛭素的不同给药途径／方式及新剂型的研究也在深入开展。现结合水蛭素的药动学／药效学特征、药理作用等方面的研究对水蛭素（包括重组水蛭素）的不同给药途径，尤其是非注射给药途径如口服、肺部、鼻腔、眼部给药等，以及相关剂型如大分子结合物注射给药缓释系统、壳聚糖一藻酸盐或PEG．藻酸盐微囊、鼻腔喷雾剂、缓释微丸、PLGA微球等的研究进展进行综述，以期为水蛭素的进一步临床应用提供科学依据。

Hirudin: administration routes and formulations

As a potent anticoagulant peptide,hirudins and recombinant hirudins(r-hirudin,also called lepirudin) have become increasing topics.To improve unfavorable features of natural hirudins,such as shorter half-life,poorer oral availability and hemorrhagic risk,the hirudin derivatives and recombinant hirudins as well as the administration routes and novel formulation of hirudin derivatives have been extensively developed.This paper reviews pharmacokinetic and pharmacodynamic features and pharmacological activities of hirudin derivatives.Various delivery systems,including non-injectable delivery routes,e.g.,oral,nasal,pulmonary and ocular vehicles,and novel sustained release systems of hirudin derivatives,e.g.,chitosan/polyethylene glycol-alginate microcapsules,PLGA microsphere and enteric coated-pellets,are also addressed,which might provide scientific rationale for further clinical applications of hirudins.