以溶解度与刺激性为指标筛选葛根素滴鼻液溶剂及增溶剂

该实验利用平衡法测定了葛根素在不同溶剂及增溶剂中的平衡溶解度,采用蟾蜍在体纤毛毒性实验考察了溶剂和增溶剂的纤毛毒性,采用大鼠长期鼻黏膜刺激性实验考察溶剂和增溶剂对鼻黏膜的刺激性。溶解度测定显示30%聚乙二醇200,10%KolliphorHS 15联用能使葛根素的溶解度达到56.44 g·L-1。以生理盐水为阴性对照,公认的有纤毛毒性的去氧胆酸钠为阳性对照,观察30%聚乙二醇200,30%聚乙二醇400,10%KolliphorHS 15及30%聚乙二醇200与10%KolliphorHS 15合用对蟾蜍上颚纤毛的影响,记录纤毛持续运动时间,结果显示30%聚乙二醇200及10%KolliphorHS 15与生理盐水相比纤毛持续运动时间没有显著性差异。以生理盐水为对照,研究纤毛毒性较小的30%聚乙二醇200及10%KolliphorHS 15的大鼠长期鼻黏膜刺激性,实验结果显示该溶剂和增溶剂对鼻黏膜刺激性较小,与生理盐水相比鼻黏膜上皮厚度及刺激指数没有显著性差异。30%聚乙二醇200和10%KolliphorHS 15能满足葛根素滴鼻液溶解度要求,纤毛毒性和刺激性小,可以作为葛根素滴鼻液较优的溶剂和增溶剂。

Selecting solvent and solubilizer for puerarin nasal drops by solubility and irritation

In order to test the equilibrium solubility of puerarin in different solvents and solubilizer,cilia toxicity and irritation of these excipient,the balance method, toad in the ciliary body toxicity and rat nasal mucosa irritation were used respectively. Results showed that puerarin solubility was 56.44 g·L^-1 in combined solvent of 30% PEG200 and 10%Kolliphor^® HS 15.With normal saline solution as negative control and sodium deoxycholate as positive control, the effects of 30%PEG200, 30%PEG 400, 10%Kolliphor^® HS 15 and combination of 30% of PEG200 and 10%Kolliphor^® HS 15 on toad palate cilium were observed and cilia movement duration was recorded. The results indicated that there was no significant difference in cilia movement duration among 30%PEG200, 10%Kolliphor^® HS 15 and normal saline group. The rats long-term nasal mucous membrane irritation of 30%PEG 400, 10%Kolliphor^® HS 15, which had no cilia toxicity, was studied, with normal saline solution as negative control. There were no significant difference revealed on rat nasal mucosa epithelial thickness among 30%PEG 400, 10%Kolliphor^® HS 15 and normal saline. Above researches showed 30%PEG 400, 10%Kolliphor^® HS 15 was ideal for solubility of puerarin nasal drops and showed a lower cilia toxicity and irritation, and can be used as the solvent and solubilizer of puerarin nasal drops.