薄荷脑鼻腔原位凝胶剂的制备及安全性研究

目的 制备薄荷脑鼻用原位凝胶剂，并对其进行安全性考察。方法 采用去乙酰结冷胶为材料制备离子敏感性原位凝胶。考察鼻腔原位凝胶对蟾蜍鼻黏膜纤毛的毒性及大鼠鼻黏膜的影响；并进行家兔皮肤刺激实验和豚鼠皮肤过敏实验，观察皮肤反应并评分。结果 薄荷脑鼻用原位凝胶剂对蟾蜍鼻黏膜纤毛无显著毒性，对大鼠鼻黏膜形态及细胞分化无显著影响；对家兔完整皮肤无刺激作用，豚鼠皮肤无过敏反应。结论 薄荷脑鼻用原位凝胶剂具有制备工艺简便、纤毛毒性低、生理相容性好的优点，开发为经鼻给药系统可行性良好。

An in situ gel system for nasal delivery of menthol: preparation and safety evaluation

Objective To prepare an in situ gel system for nasal delivery of menthol and to evaluate the safety of this formulation. Methods Menthol in situ gel was prepared with deacetylatedgellan gum. The nasal mucocilia toxicities of this formulation was evaluated using in situ toad palate model.Guinea pig skin sensitization test and the rabbit skin irritation test were conducted. Skin allergy and irritation reaction were monitored and scored. Results No significant effect on nasal mucosa ciliary movement and the morphology of rat nasal mucosa were observed.The formulation did not induce any dermal irritation in rabbits. Skin allergic reaction was not found in guinea pigs. Conclusion The preparation of menthol in situ nasal gel with low ciliary toxicity was easily achieved. This gel has good physiological flexibility.The further investigation was warranted for this formulation as an intranasal drug delivery system.