水蛭素的给药途径及其相关剂型研究进展

Hirudin: administration routes and formulations

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-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。

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 recom- binant 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 pharmaco- logical 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.