石杉碱甲新剂型研究进展

Progress in pharmaceutical studies of huperzine A

石杉碱甲是一种高效、高选择性的中枢乙酰胆碱酯酶抑制剂,其作用时间长、易透过血脑屏障、口服生物利用度高,在国内已广泛应用于阿尔采末病的治疗。目前上市的剂型主要为口服或注射的普通制剂,需多次使用,因此对于患有认知功能缺失的老年患者存在用药不便的问题。此外,多次给药还容易引起血药浓度大幅度波动,导致机体产生不良反应,因此对其新剂型的开发势在必行。本文综述了石杉碱甲新剂型相关研究进展,主要根据药物体内外释放特征、安全性、有效性等对现有的石杉碱甲口服缓控释制剂、长效缓释注射剂、缓释贴片、鼻用原位凝胶等剂型进行了比较,同时结合脑内乙酰胆碱变化水平与学习记忆关系的理论提出了新的剂型设计思路,以期为进一步开发安全、疗效可控和依从性高的新产品提供参考。

Huperzine A is a potent, highly specific inhibitor of acetylcholinesterase in central nervous system, which has been widely used in the treatment for Alzheimer＇ s disease （AD）. Huperzine A is commonly available in the market as oral or injectable formulation, which has to be given several times per day. This multitime administration is not convenient enough for the old patients with memory deficiency. It could also cause a large fluctuation of drug concentration, and may in turn induce peripheral cholinergic side effects. Therefore, it is necessary to develop novel drug formulation with optimized delivery system. In the present review, an attempt is made to discuss the current progress of huperzine A in pharmaceutics, including sustainedrelease tablet, injectable microsphere, transdermal patch and intranasal brain targeting gel. Meanwhile, novel drug administration strategy is proposed with the evidence about close association between central acetylcholine level and memory ability, aiming at offering useful information for developing more efficient and convenient huperzine A products.