基于八元瓜环对抗肿瘤药盐酸厄洛替尼溶解度的影响研究

Effect on Solubility on Antineoplastic Drug Erlotinib Hydrochloride Based on Cucurbit [8] Uril

为提高抗肿瘤药盐酸厄洛替尼的生物利用度，以盐酸厄洛替尼（ELTN）为客体、八元瓜环Q[8]为主体，利用紫外．可见吸收光谱法研究了Q[8]对盐酸厄洛替尼的超分子相互作用。考察了溶液pH对作用体系的影响，同时研究了Q[8]对盐酸厄洛替尼的增溶性和溶出度。实验结果表明，在pH〈7条件下，Q[8]与盐酸厄洛替尼能够形成包结比为2：1的稳定包结物，包结物的稳定常数为3．9×10^12L。／mol^2。Q[8]的加入能明显改善盐酸厄洛替尼的溶解度，并提高盐酸厄洛替尼的溶出度，且溶液酸性越强，效果越显著。在人工模拟胃液（pH1．2）中，包结物Q[8]-ELTN的累积溶出度提高了近14倍，说明Q[8]不仅能提高盐酸厄洛替尼的溶解性，还具有潜在的药物运输载体的特性。

To improve the bioavailability of antineoplastic drug erlotinib hydrochloride （ELTN）,with antineoplastic drug erlotinib hydrochloride as guest and cucurbit [8] uril as host in this work, the supramolecular interaction of cueurbit [8] uril with erlotinib hydrochloride was investigated by UV-Vis spectroscopy.The effects on supramolecular interaction of the solution pH and the solu- bility and dissolution rate of cucurbit [8] uril to erlotinib hydrochloride were also investigated.The results showed that under the condition of solution pH〈7,a 2：1 ratio complex was formed,and the formation constant was 3.9×10^12 L2/molE.The solubility and dissolution of erlotinib hydrochloride had a marked improvement with the added of cucurbit E 81 uril,the stronger of the acidity of the solution,the more significant the solubility and dissolution rate of cucurbit [8] uril to erlotinib hydrochloride will be.Cumula- tive release rate of complex Q[8]-ELTN was increased about 14 times in artificial gastric juice（ pH 1.2）.Solubility and dissolu- tion rate of erlotinib hydrochloride can be enhanced by eucurbit [8] uril, and cucurbit [8] uril may be preeminently potential drug carrier properties.