不同季铵化程度的N-三甲基壳聚糖透皮吸收促进作用的研究

 目的研究不同季铵化程度的N-三甲基壳聚糖(N-trimethylchitosan,TMC)对药物透皮吸收的促进作用,以判断季铵化程度对TMC发挥透皮吸收促进作用的影响。方法以壳聚糖及碘甲烷为主要原料,合成不同取代度的TMC,即TMC40和TMC60,通过1H-NMR确定其季铵化程度。以睾酮为模型药物,分别以溶液法和凝胶法考察两种不同季铵化程度TMC的透皮吸收促进作用。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%。溶液法及凝胶法两种方法的体外透皮实验结果均表明TMC60组、TMC40组及空白组的累积透过率、稳态透皮速率的作用大小顺序为TMC60组>TMC40组>空白组。结论TMC60的透皮促进作用大于TMC40,表明在一定范围内随着季铵化程度的增加,TMC透皮吸收促进作用增大。

Effect of Different Degree Quaternization of N-trimethyl Chitosan on Enhancing Penetration

OBJECTIVE To study the effect of different degree of quaternization(DQ) of N-trimethyl chitosan(TMC) on enhancing penetration.METHODS TMC40 and TMC60 were synthesized by a two-step method using chitosan and methyl-iodide. The DQ of TMC was determined by ~ 1 H-NMR. Percutaneous absorption in vitro was utilized to estimate the penetration enhancing effect of TMC40 and TMC60 using testoterone as model drug. The preparations were testoterone solutions and testoterone gels. RESULTS The DQ of TMC40 and TMC60 was 38.8% and 67.2%,respectively. The percentage of accumulative penetration(Q) and the steady penetration rate(J) were calculated. The effect order of three kinds was TMC60>TMC40>blank control.CONCLUSION The results suggest that the penetration enhancement of TMC60 is stronger than that of TMC40. With the increase of DQ, the penetration enhancing effect of TMC is increasing.