银杏内酯B前体药物的抗血小板聚集活性研究

目的考察银杏内酯B前体药物(PGB)的抗血小板聚集作用。方法采用LC-MS/MS法测定PGB在体外和体内的降解情况,并以比浊法观察PGB体外、体内给药对PAF诱导兔血小板聚集的影响。结果 PGB在体外血浆中的降解反应为表观一级反应,体内外均能迅速水解出银杏内酯B(GB);在体外、体内均呈剂量依赖性抑制PAF诱导的兔血小板聚集,体外最大抑制率分别为8.67、20.01、50.60、73.01,体内最大抑制率分别为42.24、58.03,其作用强度接近于原药GB。结论 PGB通过分解出的GB拮抗PAF受体实现血小板聚集抑制作用,是一个具有良好前景的脑血管疾病治疗前体药物。

Antiplatelet aggregative activity of prodrug of Ginkgolide B

Aim To investigate the antiplatelet aggregative activity of prodrug of Ginkgolide B(PGB).Methods In vitro and in vivo degradation of PGB were determined by LC-MS / MS method and the effect of in vitro and in vivo administration of PGB on rabbit platelet aggregation induced by PAF was observed by turbidimetry.Results PGB displayed pseudo-first-order reaction in vitro plasma and Ginkgolide B(GB) could be hydrolyzed from PGB rapidly in vitro and in vivo;dose-dependent inhibition of PAF-induced rabbit platelet aggregation was found in vitro and in vivo.The maximal inhibition rates in vitro were 8.67,20.01,50.60 and 73.01,respectively,and the maximal inhibition rates in vivo were 42.24 and 58.03.The intensity was close to parent drug GB.Conclusion Because of antagonist of PAF receptor by GB decomposed from PGB,the platelet aggregation inhibition is achieved.It suggests that PGB is one kind of therapeutic prodrug with good prospects for cerebrovascular disease.