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(N-trimethyl chitosan,TMC)对胰岛素液体栓剂体外性质的影响。方法用壳聚糖及碘甲烷为主要原料,合成不同季铵化程度的TMC,即TMC40和TMC60,通过1H-NMR确定其季铵化程度。以泊洛沙姆407和188为基质,以TMC作为黏膜吸收促进剂制备胰岛素液体栓剂,用血糖试纸测定给药后小鼠不同时间点的血糖值,TMC季铵化程度及其不同浓度(质量分数为0%,0.1%,0.5%,1%)对液体栓剂的体外胶凝温度、胶凝强度和生物黏附力影响。结果经¹H-NMR确定合成得到的TMC40,TMC60季铵化程度分别为38.8%和67.2%。同一种季铵化程度TMC,随着TMC浓度的增加,胰岛素液体栓剂的胶凝温度减小,胶凝强度和生物黏附力均增大。同一浓度的TMC,随着季铵化程度的增加,其胶凝温度升高,胶凝强度和生物黏附力均减小。结论TMC季铵化程度及其不同浓度对液体栓剂的体外性质有着显著的影响,可以通过使用不同季铵化程度的TMC和改变其浓度来改善胰岛素液体栓剂的体外性质,可能更有效的促进胰岛素的直肠吸收。

OBJECTIVE To study the effect of quaternization and concentration of N-trimethyl chitosan on the physicochemical properties of insulin liquid suppositories in vitro.METHODS Two kinds of TMC with different degrees of quaternization,ie.TMC40 and TMC60,were synthesized by a two-step method using chitosan and methyl-iodide.The degrees of quaternization of TMC was determined by¹H-NMR.P407 and P188 were used as liquid suppository bases to prepare insulin liquid suppository with TMC as the absorption enhancer.The changes of the characters of the liquid suppository in vitro were determined by measuring gel temperature,gel strength and bioadhesive force with different concentrations(0%,0.1%,0.5%,1%)and degrees of quaternization of TMC.RESULTS The degree of quaternization of TMC40 and TMC60 was 38.8% and 67.2%,respectively.With the increase of TMC concentration,there was an decrease in gelation temperature,while an increase in both of gel strength and bioadhesive force.With an increase in the degree of quaternization of the TMC,there was an increase in gelation temperature and an decrease in both of gel strength and bioadhesive force.CONCLUSION The degree of quaternization and concentration of TMC had significant influence on the properties of the liquid suppository in vitro.Adjusting of degrees of quaternization and concentration of TMC maybe improve the properties in vitro and enhance the rectal absorption of insulin.