目的 基于壳聚糖修饰β-环糊精制备载葛根素超分子凝胶（puerarin-loaded chitosan-modified β-cyclodextrin supramolecular gel，Pur@CS-β-CD Gel），优化其处方并评价其鼻腔给药及抗偏头痛效果。方法 采用单因素与Box-Behnken设计-响应面法（Box-Behnken design-response surface methodology，BBD-RSM）优化Pur@CS-β-CD Gel处方，表征其微观结构、pH值、稳定性及体外释放行为。建立慢性偏头痛大鼠模型，通过行为学指标及脑内降钙素基因相关肽（calcitonin gene-related peptide，CGRP）、5-羟色胺（5-hydroxytryptamine，5-HT）和白细胞介素-1β（interleukin-1β，IL-1β）水平评价药效。结果 最优处方为CS-β-CD与羧甲基纤维素钠质量比1∶9、总质量分数2.6%、葛根素40 mg。所得Pur@CS-β-CD Gel呈三维多孔结构，pH值6.5，稳定性良好，体外释放呈现4 h累积释放82.75%的快速释放与后续缓释特征，无明显鼻黏膜刺激性。药效实验显示，Pur@CS-β-CD Gel能显著改善偏头痛大鼠行为学表现，降低脑内CGRP和IL-1β水平，提升5-HT含量。结论 Pur@CS-β-CD Gel制备工艺可行，具备良好的鼻腔给药特性及抗偏头痛效果，为鼻腔递药系统及偏头痛治疗提供了实验依据。

Objective To develop a puerarin-loaded supramolecular gel based on chitosan-modified β-cyclodextrin (Pur@CS-β-CD Gel), optimize its formulation, and evaluate its potential for nasal delivery and anti-migraine efficacy. Methods The Pur@CS-β-CD Gel formulation was optimized using single-factor experiments and Box-Behnken design-response surface methodology (BBD-RSM). The optimized Pur@CS-β-CD Gel was characterized for its microstructure, pH value, stability, and in vitro release profile. A chronic migraine rat model was established. The therapeutic efficacy was assessed through behavioral indicators and by measuring the levels of calcitonin gene-related peptide (CGRP), 5-hydroxytryptamine (5-HT), and interleukin-1β (IL-1β) in brain tissue. Results The optimal formulation consisted of CS-β-CD and sodium carboxymethylcellulose at a mass ratio of 1:9, a total polymer concentration of 2.6%, and 40 mg of puerarin. The resulting Pur@CS-β-CD Gel exhibited a three-dimensional porous structure, a pH of 6.5, good stability, and a biphasic in vitro release profile characterized by an initial rapid release (82.75% within 4 h) followed by sustained release, with no obvious nasal-mucosal irritation. Pharmacodynamic studies demonstrated that Pur@CS-β-CD Gel significantly improved migraine-related behavioral performance in rats, reduced CGRP and IL-1β levels, and increased 5-HT content in the brain. Conclusion The Pur@CS-β-CD Gel demonstrates a feasible preparation process, favorable properties for nasal administration, and effective anti-migraine activity, providing an experimental basis for the development of novel nasal delivery systems and migraine therapies.

R283.6

陕西省重点研发计划一般项目（2024SF-YBXM-530）；陕西省科学技术协会青年人才托举计划（20250355）；陕西省中医药管理局科研项目（SZY-KJCYC-2025-ZY-009）；陕西省中医药研究院（陕西省中医医院）院级“苗圃培育计划”（2025-18）