胰岛素鼻腔给药制剂的试验研究

Studies on the preparation of insulin using in nasal cavity

目的:将胰岛素制成一个较稳定的鼻腔给药制剂,为临床提供一个初步可行的用药依据。方法:采用LGY(国外药物透皮扩散室)扩散小室法,用人的胎盘膜模拟鼻黏膜先在体外做累积溶出度试验,再用大白兔做效用试验,验证制剂的可行性及试用性,并采用不同pH值、不同温度控制制剂的稳定性,观察其最稳定的保存时间及温度。结果:本课题采用了氮酮、油酸、丙二醇为联合促透剂,聚乙二醇为基质及稳定剂,以丙三醇为保湿剂,形成一个较稳定的新制剂;本制剂的平均回收率为63.53%,体外累积溶出度6 h,达高峰为42.31%,其制剂在pH 4.0时较稳定,保存温度为2℃,放置1个月后其含量为66.59%;在动物药效试验中,皮下注射组血糖值在给药后1 h降至最低,8 h基本恢复正常;而试验组给药后2 h降至最低,维持较低血糖值的时间比皮下注射组相对较长。结论:体外试验及动物试验表明,胰岛素在促透剂的作用下可以透过鼻黏膜,但所需的剂量较大,经济上损耗大,有待于今后进一步研究。

Object： To prepare insulin into a stable preparation that can be used in nasal cavity in order to provide a feasible basis for clinic. Methods： The accumulative solubility experiment was performed with the human＇s embryolemma instead of tunica mucosa nasal at first, then the experiment of effectiveness was carried out in rabbits to study the feasibility and practicality of the preparation. The stability of the preparation was controlled by various pH and temperature, so that the most stable preserving period and temperature could be observed. Results： Azone, oleicacid and propanediol were used as combined promoter, polythylene as the stroma and stabilize, glycerol as moisturizing substance, thus formed a new stable preparation. The average resorption rate of this preparation was 63.53%, the external accumulative solubility reaches the peak which was 42.31% in 6 h. The preparation was stable at pH 4.0. When the preserving temperature was 2 ℃, laid up for a month , the content of the preparation was 66.59%. In the animal experiments, the level of blood sugar of the subcutaneous injection group was the lowest at 1 h and returned to normal at 8 h . In the experimental group, the level of blood sugar was the lowest at 2 h and the effective period was longer than that of the subcutaneous injection group. Conclusion： In vitro and animal experiments proved that insulin can penetrate tunica mucosa nasal with the help of promoters, but the doses needed was larger and the economic consumption was higher. So it is to be further studied.