β-环糊精包合物对香附四物汤挥发油中主要成分在Caco-2细胞模型中转运的影响

Effect of β-cyclodextrin inclusion complex on transport of major components of Xiangfu Siwu decoction essential oil in Caco-2 cell monolayer model

虽然香附四物汤挥发油具有较强的药理活性,但挥发油特殊的物理化学性质制约了其临床应用与药效发挥。该文采用环糊精包合技术对香附四物汤挥发油部位进行制剂处理,同时利用人源结肠腺癌细胞系Caco-2细胞单层模型,研究了香附四物汤挥发油经β-环糊精包合后主要活性成分体外跨膜转运的改变,探讨了β-环糊精包合物对以低溶解性、高渗透性为特征的生物药剂学分类系统中第Ⅱ类药物跨膜转运与吸收的影响。首次建立了UPLC-MS/MS进行香附四物汤挥发油中主要活性成分洋川芎内酯A、正丁基苯酞、藁本内酯、去氢木香内酯、α-香附酮同时测定的含量分析方法。结果表明,将香附四物汤挥发油制成β-环糊精包合物能显著提高其活性成分在体外的透膜转运与吸收,据此推测环糊精包合物对难溶性药物的口服生物利用度有一定改善作用。该文的研究内容为香附四物汤β-环糊精包合物更加深入的体内过程研究提供了一定的实验依据,同时也为其新型口服制剂的研发奠定了基础。

Although the essential oil of Xiangfu Siwu decoction（ XFSWD） has strong pharmacological activity,its special physical and chemical properties restrict the clinical application and curative effect. In this paper,Xiangfu Siwu decoction essential oil（ XFSWO） was prepared by forming inclusion complex with β-cyclodextrin（ β-CD）. The present study is to investigate the effect of β-CD inclusion complex on the transport of major components of XFSWO using Caco-2 cell monolayer model,thus to research the effect of this formation on the absorption of drugs with low solubility and high permeability,which belong to class 2 in biopharmaceutics classification system. A sensitive and rapid UPLC-MS / MS method was developed for simultaneous quantification of senkyunolide A,3-n-butylphthalide,Z-ligustilide,dehydrocostus lactone and α-cyperone,which are active compounds in XFSWO. The transport parameters were analyzed and compared in free oil and its β-CD inclusion complex. The result revealed that the formation of XFSWO / β-CD inclusion complex has significantly increased the transportation and absorption of major active ingredients than free oil. Accordingly,it can be speculated that cyclodextrin inclusion complex can improve bioavailability of poorly water-soluble drugs. Above all these mentioned researches,it provided foundation and basis for physiological disposition and pharmaceutical study of XFSWD.