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葛根素-壳聚糖修饰β-环糊精鼻用超分子凝胶的制备及抗偏头痛药效评价

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宗时宇 ¹,,², , 王苗 ³ , 马鑫宇 ⁴ , 刘烁 ⁴ , 任佳 ⁴ , 程云龙 ¹,,², , 王春柳 ¹,,²,

中草药 | 药剂与工艺 2026,57(16): 6320-6328

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中草药 |药剂与工艺 2026 , 57 (16) : 6320 -6328

葛根素-壳聚糖修饰β-环糊精鼻用超分子凝胶的制备及抗偏头痛药效评价

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宗时宇¹,,²,, 王苗³, 马鑫宇⁴, 刘烁⁴, 任佳⁴, 程云龙¹,,²,, 王春柳¹,,²,

作者信息

^1.陕西省中医药研究院, 陕西西安 710003

^2.陕西省中医药研究院中药新型给药重点研究室, 陕西西安 710003

^3.西安大兴医院, 陕西西安 710082

^4.陕西中医药大学, 陕西咸阳 712046

^5.陕西省中医药研究院, 陕西西安 710003

^6.陕西省中医药研究院中药新型给药重点研究室, 陕西西安 710003

通讯作者:

王春柳

作者简介:

宗时宇: 宗时宇,女,助理研究员,主要从事中药药效物质基础与新型给药系统研究。E-mail:zongsy114@163.com

Preparation and anti-migraine pharmacodynamic evaluation of puerarin-loaded chitosan-modified β-cyclodextrin nasal supramolecular gel

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出版时间: 2026-08-28 doi: 10.7501/j.issn.0253-2670.2026.16.009

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摘要

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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。

关键词

葛根素 / 超分子凝胶 / 工艺优化 / 鼻腔给药 / 慢性偏头痛 / 药效评价

Abstract

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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.

Key words

puerarin / supramolecular gel / process optimization / nasal administration / chronic migraine / pharmacodynamic evaluation

引用本文

宗时宇, 王苗, 马鑫宇, 刘烁, 任佳, 程云龙, 王春柳. 葛根素-壳聚糖修饰β-环糊精鼻用超分子凝胶的制备及抗偏头痛药效评价. 中草药, 2026 , 57 (16) : 6320 -6328 . DOI: 10.7501/j.issn.0253-2670.2026.16.009

ZONG Shiyu, WANG Miao, MA Xinyu, LIU Shuo, REN Jia, CHENG Yunlong, WANG Chunliu. Preparation and anti-migraine pharmacodynamic evaluation of puerarin-loaded chitosan-modified β-cyclodextrin nasal supramolecular gel[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (16) : 6320 -6328 . DOI: 10.7501/j.issn.0253-2670.2026.16.009

基金

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陕西省重点研发计划一般项目
陕西省科学技术协会青年人才托举计划
陕西省中医药管理局科研项目
陕西省中医药研究院（陕西省中医医院）院级“苗圃培育计划”

参考文献

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参考文献引证文献

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Wang M, Ma X Y, Zong S Y, et al. The prescription design and key properties of nasal gel for CNS drug delivery: A review [J]. Eur J Pharm Sci, 2024, 192: 106623.

张庆美. 葛根素片联合天麻素片对风热证偏头痛模型大鼠CGRP及其受体表达的影响[D]. 北京: 北京中医药大学, 2019.

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Zhu J H, Chen X, Chen Y, et al. Preparation and characterization of ternary polysaccharide hydrogels based on carboxymethyl cellulose, carboxymethyl chitosan, and carboxymethyl β-cyclodextrin [J]. Int J Biol Macromol, 2024, 271: 132604.

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Sipos B, Bella Z, Gróf I, et al. Soluplus^® promotes efficient transport of meloxicam to the central nervous system via nasal administration [J]. Int J Pharm, 2023, 632: 122594.

Pires P C, Paiva-Santos A C, Veiga F. Liposome-derived nanosystems for the treatment of behavioral and neurodegenerative diseases: The promise of niosomes, transfersomes, and ethosomes for increased brain drug bioavailability [J]. Pharmaceuticals, 2023, 16(10): 1424.

黄建花, 陈玉柱, 佟菲, 等. 偏头痛持续状态的诊断及治疗策略进展[J]. 中国疼痛医学杂志, 2021, 27(1): 60-63.
Zong S Y, Wang M, Ma X Y, et al. Development and characterization of Magnoliae Flos essential-oil-loaded nanoemulsion: A spatiotemporal nose-to-brain delivery enhancer for solution and gel-based pharmaceutical formulations [J]. Pharmaceutics, 2025, 17(12):1535.
Li Y, Wang C L, Zong S Y, et al. The trigeminal pathway dominates the nose-to-brain transportation of intact polymeric nanoparticles: Evidence from aggregation-caused quenching probes [J]. J Biomed Nanotechnol, 2019, 15(4): 686-702.
施之琪, 李卿, 贾凡, 等. 齐墩果酸液晶纳米温敏凝胶大鼠鼻腔给药药动学及脑靶向性研究[J]. 中国医院药学杂志, 2025, 45(12): 1363-1369.
Wang M, Ma X Y, Zong S Y, et al. The prescription design and key properties of nasal gel for CNS drug delivery: A review [J]. Eur J Pharm Sci, 2024, 192: 106623.
张庆美. 葛根素片联合天麻素片对风热证偏头痛模型大鼠CGRP及其受体表达的影响[D]. 北京: 北京中医药大学, 2019.
叶盛航, 朱卫丰, 臧振中, 等. 葛根素-大豆苷元包合物纳米晶的制备及性能研究[J]. 中国药学杂志, 2024, 59(22): 2159-2168.
Li X X, Li S L, Ma C, et al. Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia [J]. Drug Deliv, 2022, 29(1):1282-1298.
Feng J, Li F Z, Zhao Y M, et al. Brain pharmacokinetics of tetramethylpyrazine after intranasal and intravenous administration in awake rats [J]. Int J Pharm, 2009, 375(1/2): 55-60.
Pradhan P, Rai V K, Halder J, et al. Development and characterization of chitosan nanoparticles containing quercetin-β-cyclodextrin inclusion complex for improved solubility, brain targeting, and neuroprotective potential against epilepsy [J]. AAPS PharmSciTech, 2025, 26(5): 124.
Cama E S, Catenacci L, Perteghella S, et al. Design and development of a chitosan-based nasal powder of dimethyl fumarate-cyclodextrin binary systems aimed at nose-to-brain administration. A stability study [J]. Int J Pharm, 2024, 659: 124216.
Zhu J H, Chen X, Chen Y, et al. Preparation and characterization of ternary polysaccharide hydrogels based on carboxymethyl cellulose, carboxymethyl chitosan, and carboxymethyl β-cyclodextrin [J]. Int J Biol Macromol, 2024, 271: 132604.
刘新国, 舒翔. 星点设计-效应面法优选磷酸川芎嗪鼻用原位凝胶基质处方的研究[J]. 中国医院药学杂志, 2019, 39(21): 2168-2171.
Mashabela L T, Maboa M M, Miya N F, et al. A comprehensive review of cross-linked gels as vehicles for drug delivery to treat central nervous system disorders [J]. Gels, 2022, 8(9): 563.
De Gaetano F, D’Avanzo N, Mancuso A, et al. Chitosan/ cyclodextrin nanospheres for potential nose-to-brain targeting of idebenone [J]. Pharmaceuticals, 2022, 15(10): 1206.
Wang S X, Wei Y P, Wang Y, et al. Cyclodextrin regulated natural polysaccharide hydrogels for biomedical applications-a review [J]. Carbohydr Polym, 2023, 313: 120760.
Wang Y Q, Wang L M, Han L F, et al. A promising strategy of brain targeted delivery for the treatment of Parkinson’s disease: Cyclodextrin supramolecular inclusion complex based thermosensitive gel [J]. J Pharm Anal, 2025, 15(5): 101102.
Kashif M U R, Sohail M, Ali Khan S, et al. Chitosan/guar gum-based thermoreversible hydrogels loaded with pullulan nanoparticles for enhanced nose-to-brain drug delivery [J]. Int J Biol Macromol, 2022, 215:579-595.
Agrawal M, Saraf S, Saraf S, et al. Stimuli-responsive in situ gelling system for nose-to-brain drug delivery [J]. J Control Release, 2020, 327: 235-265.
陈函, 廉婷, 杜远东, 等. 鼻用葛根素脂质体温敏凝胶剂的制备与质量评价[J]. 化工科技, 2020, 28(5): 41-46.
甘慧琴, 梅陈松, 关志宇, 等. 葛根多糖载葛根素纳米粒温敏凝胶的制备及其药动学研究[J]. 中草药, 2024, 55(21): 7238-7247.
Zhang Y Y, Li Q, Hu J L, et al. Nasal delivery of cinnarizine thermo- and ion-sensitive in situ hydrogels for treatment of microwave-induced brain injury [J]. Gels, 2022, 8(2): 108.
Sipos B, Bella Z, Gróf I, et al. Soluplus^® promotes efficient transport of meloxicam to the central nervous system via nasal administration [J]. Int J Pharm, 2023, 632: 122594.
Pires P C, Paiva-Santos A C, Veiga F. Liposome-derived nanosystems for the treatment of behavioral and neurodegenerative diseases: The promise of niosomes, transfersomes, and ethosomes for increased brain drug bioavailability [J]. Pharmaceuticals, 2023, 16(10): 1424.

2026年第57卷第16期

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文章信息

doi: 10.7501/j.issn.0253-2670.2026.16.009

接收时间：2026-02-24
首发时间：2026-10-22
出版时间：2026-08-28

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收稿日期：2026-02-24

基金

陕西省重点研发计划一般项目

陕西省科学技术协会青年人才托举计划

陕西省中医药管理局科研项目

陕西省中医药研究院（陕西省中医医院）院级“苗圃培育计划”

作者信息

^1.陕西省中医药研究院, 陕西西安 710003

^2.陕西省中医药研究院中药新型给药重点研究室, 陕西西安 710003

^3.西安大兴医院, 陕西西安 710082

^4.陕西中医药大学, 陕西咸阳 712046

^5.陕西省中医药研究院, 陕西西安 710003

^6.陕西省中医药研究院中药新型给药重点研究室, 陕西西安 710003

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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