壳聚糖—半胱氨酸轭合物对胰岛素酶降解和降血糖作用的影响

摘要/Abstract

摘要： 目的研究壳聚糖-半胱氨酸轭合物对胰岛素消化酶降解的抑制作用, 及其对胰岛素口服降血糖的促进作用. 方法合成壳聚糖-半胱氨酸轭合物,体外实验考察其对α-糜蛋白酶和胰蛋白酶降解胰岛素的抑制作用. O1/O2乳化溶剂挥发法制备胰岛素肠溶微球,考察壳聚糖-半胱氨酸轭合物对胰岛素溶液和肠溶微球大鼠灌胃后降血糖作用的影响. 结果所合成的壳聚糖-半胱氨酸轭合物巯基含量为200 μmol·g^-1 polymer,体外实验对酶降解胰岛素有明显的保护作用:不加壳聚糖-半胱氨酸轭合物的对照组胰岛素溶液可分别在1 h和5 h内被α-糜蛋白酶和胰蛋白酶完全降解; 含4mg·mL^-1轭合物的同浓度的胰岛素溶液在相同浓度的酶溶液中经过相同时间,胰岛素剩余量均大于75%.所制备的胰岛素肠溶微球载药量7%,大鼠灌胃给予壳聚糖-半胱氨酸轭合物85 mg·kg^-1,可增强胰岛素溶液或肠溶微球的口服降血糖作用.结论壳聚糖-半胱氨酸轭合物对胰岛素口服制剂降血糖作用的增强可能与其酶抑制作用有关.

关键词: 壳聚糖-半胱氨酸轭合物, 壳聚糖-半胱氨酸轭合物, 壳聚糖-半胱氨酸轭合物, 胰岛素, 胰岛素, 胰岛素, 酶降解, 酶降解, 酶降解, 肠溶微球, 肠溶微球, 肠溶微球, 降血糖作用, 降血糖作用, 降血糖作用

Abstract: Aim To evaluate the inhibitory effect of chitosan-cysteine conjugate on enzymatic degradation and hypogly-cemic enhancement effect of insulin. Methods Chitosan-cysteine conjugate was synthesized. The protective effect of the conjugate against degradation of insulin by α-chymotrypsin and trypsin was evaluated in vitro. Insulin enteric-microspheres were prepared by using O1/O2 emulsion solvent evaporation method. The hypoglycemic enhancement effect of the conjugate was studied by oral administration of insulin solution or enteric-microspheres to rats. Results The thiol group content of the synthesized conjugate was about 200 μmol·g^-1 polymer, which showed a strong protective effect on insulin from enzymatic degradation in vifro. Almost all the insulin incubated in α-chymotrypsin solution or trypsin solution without chitosan-cysteine conjugate was degraded entirely within 1 h and 5 h respectively, whereas above 75% of insulin remained in the same content of the enzymatic solution containing 4 mg·mL^-1 conjugate. The drug loading of insulin enteric-microspheres was about 7%.In vivo experiment, chitesan-cysteine conjugate (85 mg·kg^-1) prolonged the hypoglycemic time of insulin solution or enter-ic-microspheres when administered simultaneously with the absorption enhancer SNAC. Conclusion Chitosan-cysteine con-jugate has a marked inhibitory effect on the enzymatic degradation of insulin in vitro, and it displays a significant hypoglyce-mic enhancement effect on insulin oral formulation in vivo.

Key words: chitosan-cysteine conjugate, chitosan-cysteine conjugate, insulin, insulin, enzymatic degradation, enzymatic degradation, enteric-microspheres, enteric-microspheres, hypoglycemic enhancement, hypoglycemic enhancement

中图分类号:

R944

R977.15

Supporting: Foundation item: National Natural Science Foundation of China, Key Project (39930200).

祁荣, 平其能^*, 徐瑞阳, 石勇平. 壳聚糖—半胱氨酸轭合物对胰岛素酶降解和降血糖作用的影响[J]. .

QI Rong, PING Qi-neng^*, XU Rui-yang, SHI Yong-ping. Effect of Chitosan-Cysteine Conjugate on Enzymatic Degradation and Hypoglycemic effect of Insulin[J]. .

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