Wang Ling, Jiang Xuehua, Li Chenrui, Ren Jing
Institution of Clinical Pharmacological, West China Second University Hospital, Sichuan University, Chengdu, P.R. China.
Arch Pharm Res. 2007 Aug;30(8):1020-6. doi: 10.1007/BF02993972.
In this paper, the effect of the chemically modified cyclodextrin [namely, 2-hydroxypropyl-beta-cyclodextrin, (HP-beta-CD)] on the aqueous solubility, dissolution rate, and intestinal permeability of the tanshinone IIA (TS) was investigated. The corresponding inclusion complex of TS-HP-beta-CD at the molar ratio of 1:1 was obtained by coevaporation. The solubility of complexed TS in water at 37+/-0.1 centi-degree was 17 times greater than that for the uncomplexed drug. The dissolution rate of TS was significantly increased by the complexation with HP-beta-CD, due to its solubilizing activity. The everted intestinal sac technique in rats was used to study the absorption behavior studies of TS and this complexation through the intestinal tissues. The permeability rates of TS across the intestinal epithelial membrane were enhanced by the formation of inclusion complex with HP-beta-CD about 89, 97 and 82 times of the uncomplexed TS in duodenum, jejunum and ileum, respectively. It was revealed that the absorption rate-limiting step of TS might be the dissolution process. The present results indicated the potential use of HP-beta-CD to improve the gastrointestinal tract absorption of TS.
本文研究了化学修饰的环糊精[即2-羟丙基-β-环糊精（HP-β-CD）]对丹参酮IIA（TS）的水溶性、溶解速率和肠道渗透性的影响。通过共蒸发获得了摩尔比为1:1的TS-HP-β-CD相应包合物。在37±0.1摄氏度下，络合后的TS在水中的溶解度比未络合药物的溶解度大17倍。由于HP-β-CD的增溶活性，TS与HP-β-CD络合后溶解速率显著提高。采用大鼠外翻肠囊技术研究了TS及其通过肠组织的这种络合作用的吸收行为。在十二指肠、空肠和回肠中，TS与HP-β-CD形成包合物后，其跨肠上皮膜的渗透速率分别提高到未络合TS的约89、97和82倍。结果表明，TS的吸收限速步骤可能是溶解过程。目前的结果表明HP-β-CD在改善TS胃肠道吸收方面具有潜在应用价值。
