大环化合物作为药物增溶剂的应用

Application of Macrocyclic Compounds as Drug Solubilizers

药物研发的过程中,越来越多的化合物存在溶解性低的问题,因此提高药物溶解度是目前迫切需要解决的问题。环糊精、杯芳烃、葫芦脲等大环化合物可以通过主客体作用形成包合物从而增加难溶性药物的水溶性。本文介绍了几种大环化合物在药物增溶领域的应用。首先,基于大环化合物化学结构和空腔属性的差异,列举了它们可增溶药物的种类和范围;其次,主客体的动态可逆包合作用还能改善药物稳定性、溶出速率等,从而使药物的生物利用度进一步提升;另外,补充了大环化合物的相关毒理学数据,这增加了其作为药物辅料批准上市的可能性;最后,总结了大环化合物作为增溶剂存在的问题,并指出空腔尺寸的局限和更全面的安全性评估是未来研究的方向。

In the process of drug research and development,the number of compounds with low solubility has increased,and it is urgent to solve the problem of drug solubility in the pharmaceutical industry.Macrocyclic compounds such as cyclodextrin,calixarene and cucurbituril can form host-guest inclusion complex,thus acting as solubilizers for poorly soluble drugs.This paper introduces the application of macrocyclic compounds in improving the solubility of drugs by host-guest interaction.Firstly,due to the differences of macrocyclic compounds in structure and properties,the types of encapsulated drugs are overviewed.Secondly,the host-guest complex by dynamic reversible inclusion can enhance the stability and dissolution rate,thereby further improving the bioavailability of drugs.In addition,the toxicological data of macrocyclic compounds are presented,thus allowing the marketability of macrocyclic compounds as excipients.Lastly,the limitations of macrocyclic compounds as drug solubilizers,such as the restricted dimension of the cavity and the more comprehensive safety assessment are summarized.