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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 effects of adjuvants such as sodium lauryl sulfate, disodium edetate, poloxamer 188, sodium octanoate, hydroxypropyl-β-cyclodextrin and β-cyclodextrin Colon absorption enhance the role. Methods Caco-2 cell model and rat model of one-way intestine perfusion were used to evaluate the effects of different concentrations of these excipients on raltitrexate-induced colonic absorption. The effects of β-CD-containing raltitrexed colon- In vitro release characteristics of p H and its distribution in rat gastrointestinal tract. Results 1.8% β-CD increased the penetration of raltitrexed 40.26 times (P_ (app)) and 3.44 times (P_ (eff)) in the two models with less adverse reactions, The colonies of raltegrase colon adhesive patch did not release the drug under p H 1.0,6.8, but released the drug under the condition of p H 7.8, and the drug release pattern accorded with Higuchi model. After oral administration, the tablet was safe Through the stomach and small intestine, located in the colon drug delivery, compared with the ordinary tablets, raltetmetric distribution in the colon tissue 24 h cumulative increase of 6.3 times. Conclusion β-CD can promote the absorption of raltitrexed in the colon. The preparation of β-CD containing raltitrexed colon-specific adhesive patch can significantly improve the distribution of raltitrexed in colon.