β-环糊精对雷替曲塞结肠吸收的促进作用  

Enhancement effect of β-cyclodextrin to Raltitrexed in colonic absorption

作　　者：那馨竹[1] 尹宗宁[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2016年第5期462-466,共5页West China Journal of Pharmaceutical Sciences

摘　　要：目的考察辅料十二烷基硫酸钠、依地酸二钠、泊洛沙姆188、辛酸钠、羟丙基-β-环糊精、β-环糊精(β-CD)对雷替曲塞结肠吸收的促进作用。方法通过Caco-2细胞模型和大鼠在体单向肠灌流模型评价不同浓度的上述辅料对雷替曲塞促结肠吸收的作用;研究含β-CD的雷替曲塞结肠定位黏附片在不同p H条件下的体外释放特性及在大鼠胃肠道组织的分布。结果 1.8%β-CD可使雷替曲塞在两种模型上的渗透性分别提高40.26倍(P_(app))和3.44倍(P_(eff)),且不良反应较小;含β-CD的雷替曲塞结肠定位黏附片在p H 1.0、6.8条件下不释放药物,而在p H 7.8的条件下释放药物,释药规律符合Higuchi模型;大鼠口服给药后,片剂可安全通过胃和小肠,定位于结肠释药,与普通片相比,雷替曲塞在结肠组织中24 h的累积分布量提高6.3倍。结论β-CD可以促进雷替曲塞在结肠处的吸收,制备含有β-CD的雷替曲塞结肠定位黏附片可显著地提高雷替曲塞在结肠组织中的分布。OBJECTIVE To investigate the enhancement effect of sodium lauryl sulfate, disodium edetate, poloxamer 188, sodium caprylate,hydroxypropyl -β- cyclodextrin and β- cyclodextrin （ β- CD） to Rahitrexed in colonic absorption. METHODS The enhancement effect of these exeipients to Raltitrexed in colonic absorption were evaluated using Caco - 2 cell model and in situ colonic perfusion model. The drug release of the tablets in vitro was measured in the different pHs and the gastrointestinal distribution in vitro was investigated after the oral administration in rats. RESULTS 1.8% β- CD increased the permeability of Rahitrexed in the two models in ratios of 40.26 （ Papp ） and 3.44 （Peff） with low toxicities. The results of dissolution experiment in vitro indicated that no drug released from the tablets in pH 1.0 and pH 6.8. While in pH 7.8, the Rahitrexed was released follow the Higuchi model. In vivo study showed that after oral administration in the rats, colon - specific bio - adhesive tablets were safe through the stomach and small intestine, and released Raltitrexed in the colon. Compared with the common tablets, the accumulated distribution of Raltitrexed in the colon tissues for 24 h increased with a ratio of 6.30. CONCLUSION β- CD can enhance the absorption of Raltitrexed in the colon and the prepared oral colon - specific bio - adhesive tablets containing 13 - CD can significantly promote the distribution of Raltitrexed in the colon tissues.

关 键 词：Β-环糊精 雷替曲塞 吸收促进 结肠定位 黏附 体外释放 组织分布 

分 类 号：R94[医药卫生—药剂学]