Wang Ling, Lai Yan, Li Chenrui, Jiang Xuehua
Department of Clinical Pharmacy, Key Laboratory of Drug Targeting of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
PDA J Pharm Sci Technol. 2009 Sep-Oct;63(5):390-400.
In this paper, the effect of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the intestinal permeability of the tanshinone IIA (TS) was investigated. The inclusion complex was obtained at the molar ratio of 1:1 by lyophilization and characterized by differential scanning calorimetry and phase solubility studies. Using the in situ intestinal perfusion technique, the absorption behaviors of TS and its inclusion complex were investigated at a series of concentration levels in three separate segments of the small intestine. Using the perfusion model, it was demonstrated that the absorption of TS, whether it was free or complexed, was independent of both the concentration and the intestinal site. The permeability rates of TS across the intestinal epithelial membrane were enhanced about 7 times and the fraction absorbed was increased approximately 9-fold by the formation of the inclusion complex with HP-beta-CD at each intestinal segment. By measuring the permeability results of Lucifer yellow, we propose that the increased permeability across intestinal membrane by HP-beta-CD plays an important role in enhanced TS absorption. Meanwhile, the morphological studies using HP-beta-CD did not reveal significant tissue damage in any of the intestinal segments. The results obtained support the use of HP-beta-CD to improve the gastrointestinal tract absorption of TS.
本文研究了2-羟丙基-β-环糊精（HP-β-CD）对丹参酮IIA（TS）肠道通透性的影响。通过冻干法以1:1的摩尔比获得包合物，并通过差示扫描量热法和相溶解度研究对其进行表征。采用原位肠灌注技术，在小肠的三个不同节段以一系列浓度水平研究了TS及其包合物的吸收行为。利用灌注模型证明，TS无论是游离态还是络合态，其吸收均与浓度和肠道部位无关。在每个肠段，与HP-β-CD形成包合物后，TS跨肠上皮膜的渗透率提高了约7倍，吸收分数增加了约9倍。通过测量荧光素黄的通透性结果，我们认为HP-β-CD增加的跨肠膜通透性在增强TS吸收中起重要作用。同时，使用HP-β-CD的形态学研究未发现任何肠段有明显的组织损伤。所得结果支持使用HP-β-CD改善TS在胃肠道的吸收。
