天然产物研究与开发 ›› 2026, Vol. 38 ›› Issue (5): 965-977.doi: 10.16333/j.1001-6880.2026.5.005 cstr: 32307.14.1001-6880.2026.5.005

• 研究论文 • 上一篇    下一篇

基于“油-水”协同的羌活全成分微乳凝胶构建及其抗类风湿性关节炎研究

杨  晨,欧阳辉发,吴灵娇,袁兴钟滟,李林致,吴佳颖,胡慧玲*   

  1. 成都中医药大学药学院/现代中药产业学院 西南特色中药资源国家重点实验室,成都 611137
  • 出版日期:2026-05-26 发布日期:2026-05-26
  • 基金资助:
    国家中医药管理局中医药创新团队及人才支持计划(ZYYCXTD)

Construction of a Notopterygii Rhizoma total constituents microemulsion gel based on oil-water synergy and its anti-rheumatoid arthritis study

YANG Chen,OUYANG Hui-fa,WU Ling-jiao,YUAN Xing-zhong-yan,LI Lin-zhi,WU Jia-ying,HU Hui-ling*   

  1. State Key Laboratory of Southwestern Traditional Chinese Medicine Resources,School of Pharmacy/ School of Modern Traditional Chinese Medicine Industry,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
  • Online:2026-05-26 Published:2026-05-26

摘要:

基于资源充分利用和“药辅合一”理念,将羌活的关键药效部位—挥发油作为油相制备羌活挥发油微乳(Notopterygii Rhizoma volatile oil-microemulsion,NVO-ME),再与其蒸馏后的水提液协同开发为外用微乳凝胶(Notopterygii Rhizoma extract microemulsion gel,NE-ME-gel)用于类风湿性关节炎的治疗。对NVO-ME和NE-ME-gel进行理化性质表征,并考察NE-ME-gel的透皮性能和皮肤刺激性。通过完全弗氏佐剂建立关节炎大鼠模型来探究NE-ME-gel的药效。表征实验表明,NVO-ME平均粒径为17.96 ± 0.52 nm,多分散系数为13.2% ± 0.6%,乳滴呈球状无粘连,傅里叶变换红外光谱显示有效成分被成功包载。制备的NE-ME-gel pH显弱酸性,黏度适中,透皮特性为低渗透-高滞留型,且无皮肤刺激性,满足外用给药制剂要求。在佐剂性关节炎大鼠模型中,NE-ME-gel显著缓解足爪肿胀、改善关节病理损伤,下调血清肿瘤坏死因子-α(tumor necrosis factor-αTNF-α)、白细胞介素-1β(interleukin-1βIL-1β)、IL-6及抗环瓜氨酸肽(anti-cyclic citrullinated peptide,anti-CCP)抗体水平(P < 0.001),显著降低TNF-α、IL-1β、IL-6在滑膜组织中的表达(P < 0.001),并且肝肾功能相关天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、尿素氮(blood urea nitrogen,BUN)、和肌酐(creatinine,CRE)的水平无变化,具有良好的安全性。综上,本研究制备的NE-ME-gel质量可控,稳定性良好且安全,可通过抑制炎症反应来治疗类风湿性关节炎。

关键词: 羌活, 提取物, 微乳凝胶, 透皮给药, 类风湿性关节炎

Abstract:

Based on the concept of full resource utilization and“the integration of medicinal and adjuvant substances”, the Notopterygii Rhizoma volatile oil microemulsion (NVO-ME) was prepared using the volatile oil, which is the main medicinal part, as the oil phase. The NVO-ME and the after-distillation aqueous extract were then combined to develop a Notopterygii Rhizoma extract microemulsion gel (NE-ME-gel), intended for the treatment of rheumatoid arthritis. The physicochemical properties of NVO-ME and NE-ME-gel were characterized, and the transdermal performance and skin irritancy of NE-ME-gel were investigated. An arthritis rat model was established using complete Freund's adjuvant to evaluate the pharmacodynamic effects of NE-ME-gel. Characterization experiments showed that the NVO-ME had an average particle size of 17.96 ± 0.52 nm, a polydispersity index of 13.2% ± 0.6%, spherical emulsion droplets without adhesion, and Fourier transform infrared spectroscopy results indicated the successful encapsulation of the active ingredients. After preparation into NE-ME-gel, the formulation exhibited weak acidity, moderate viscosity, and transdermal characteristics of low permeability and high retention, with no skin irritation, meeting the requirements for topical drug delivery. In the adjuvant-induced arthritis rat model, NE-ME-gel significantly alleviated paw swelling, improved joint pathological damage, and downregulated serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and anti-cyclic citrullinated peptide (anti-CCP) antibodies (P < 0.001). It also significantly reduced the expression of TNF-α, IL-1β, and IL-6 in synovial tissue (P < 0.001), with no changes in liver and kidney function-related aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (CRE) levels, demonstrating good safety. In conclusion, the NE-ME-gel developed in this study exhibits well-controlled quality, favorable stability, and a good safety profile. It treats rheumatoid arthritis by suppressing the inflammatory response.

Key words: Notopterygii Rhizoma; extract, microemulsion gel, transdermal drug delivery, rheumatoid arthritis

中图分类号:  R283.6