N-三甲基壳聚糖对胰岛素液体栓剂直肠吸收的促进作用研究  

Effect of N-Trimethyl Chitosan on Rectal Absorption of Insulin Liquid Suppositories

作　　者：何文[1] 代文兵[2] 吴燕[3] 张冕[2] 李菁[2] 

机构地区：[1]武汉大学人民医院药学部,武汉430060 [2]武汉大学药学院,武汉430072 [3]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药学杂志》2006年第16期1240-1243,共4页Chinese Pharmaceutical Journal

摘　　要：目的研究不同季铵化程度及其不同浓度的N-三甲基壳聚糖(-Ntrimethyl chitosan,TMC)对胰岛素液体栓剂药物直肠吸收的影响。方法以壳聚糖及碘甲烷为主要原料合成两种季铵化程度的TMC,即TMC40和TMC60。以泊洛沙姆407(P407)和泊洛沙姆188(P188)(15%∶20%)为基质,分别以浓度为0,0.1%和0.5%的TMC40或TMC60作为黏膜吸收促进剂制备胰岛素液体栓剂。以2 g.kg-1(相当于胰岛素200 U.kg-1)给药剂量直肠给糖尿病小鼠不同的胰岛素液体栓剂,用血糖试纸测定给药后糖尿病小鼠不同时间点的血糖值,计算出各制剂的AUC0→4,进行比较。结果未加TMC的胰岛素液体栓剂没有降血糖的作用;加入了TMC的液体栓剂均能显著降低糖尿病小鼠的血糖水平,且随着TMC浓度的增加,促进作用增强,而当浓度相同时,TMC60的作用大于TMC40,其中含有0.5%TMC60的胰岛素液体栓剂降血糖的作用最好,在1.5 h时血糖降至最低,为初始水平的(19.6±6.5)%,其AUC0→4为(108.2±4.6)。结论TMC可以促进胰岛素的直肠吸收,且随着其季铵化程度的增加,其促吸收作用增强。OBJECTIVE To study the eflect of degree of quatemization and concentration of N-trimelhyl chitosan on the rectal absorption of insulin liquid suppositories, METHODS Two kinds of TMC with different degree of quatemization, i, e, TMC40 and TMC60, were synthesized by a two-step method using chitosan and methyl-iodide. P407 and P188（15/20%） were used as the base to prepare insulin liquid suppository with TMC40 or TMC60 at different concentration（ 0%, 0.1%, 0.5 % ） as the absorption enhancer. Liquid suppositories were rectally administered to dialytic mice with a dose of 2 g· kg^-1 （ equals to insulin 200 u· kg^ -1）, and then the blood glucose level in different time were determined by blood glucose test strip and calculated the AUC0→4. RESULTS The liquid suppository without TMC had no hypoglycemic effect. All the liquid suppositories with TMC had significant hypoglycemic effect（ P 〈 0.05）. With the increase of the TMC concentration, the enhancing effect decreased. At the same concentration, TMC60 had better hypoglycemic effect than TMC40. The liquid suppository with 0.5% TMC60 had the best hypoglycemic effect. At 1.5 h, the blood glucose level was at nadir with（ 19.6 ± 6.5） % of the original blood glucose level. The AUCo,4 was （108.2 ± 4.6）. CONCLUSION TMC could enhance the rectal absorption of insulin. The degree of quatemization and concentration of TMC could significantly influence on the rectal absorption of insulin.

关 键 词：液体栓剂 N-三甲基壳聚糖 胰岛素 季铵化程度 

分 类 号：R944.23[医药卫生—药剂学]