药学研究2025，Vol.44Issue(7)：640-648,9.DOI:10.13506/j.cnki.jpr.2025.07.003
罗通定立方液晶凝胶构建与初步药效学考察
Construction of l-tetrahy-dropalmatine cubic liquid crystal gel and preliminary pharmacodynamics investigation
摘要
Abstract
Objective To prepare l-tetrahy-dropalmatine cubic liquid crystal gel(L-THP-CLCG)and evaluate its in vitro characteristics and preliminary pharmacodynamics.Methods A ternary phase diagram method was employed using glyceryl monooleate(GMO),anhydrous ethanol(AE),and water to preliminarily determine the optimal formulation region of L-THP-CLCG.The optimal formulation was further refined based on in vitro transdermal penetration studies.Additionally,the best penetration enhancer was selected from azone,propylene glycol,and menthol,and the skin retention profile over different time points was assessed.The preparation process was optimized using a single-factor experiment.The structure of L-THP-CLCG was characterized using polarized light microscopy,small-angle X-ray scattering(SAXS)and environmental scanning electron microscope(ESEM),while its stability and rheological properties were also evaluated.Furthermore,its analgesic effects were investigated using the hot plate test and acetic acid-induced writhing test in mice.Results The optimal formulation of L-THP-CLCG was determined as GMO∶AE∶water=63∶7∶30,with the preferred preparation process being vortexing at 60 ℃ for 3 minutes,followed by sealed storage in a 25 ℃ incubator under light protection for 24 hours.The optimal penetration enhancer was 3％ menthol,resulting in a 24-hour cumulative transdermal penetration of(1 241.39±48.83)μg·cm-2,which was significantly higher than that of the control group(P＜0.01).The skin retention study showed a gradual increase in retention from 0.5 to 10 h,reaching a maximum of(49.78±3.70)μg·cm-2 at 10 h,suggesting sustained accumulation in the skin.The obtained L-THP-CLCG was a colorless,transparent,and stable cubic liquid crystal gel with an internal double-diamond(Pn3m)lattice structure.Pharmacodynamic evaluations demonstrated that L-THP-CLCG significantly prolonged the paw-licking latency in the hot plate test and increased the pain threshold in the acetic acid-induced writhing test,reducing the number of writhes compared to the model group(P＜0.01).Conclusion The L-THP-CLCG prepared in this study exhibited a simple and stable preparation process,good transdermal penetration properties,and significant analgesic effects,providing a valuable reference for the development of transdermal delivery formulations of l-tetrahy-dropalmatine.关键词
罗通定/立方液晶凝胶/促渗剂/体外透皮/镇痛Key words
l-tetrahy-dropalmatine/Cubic liquid crystal gel/Penetration enhancer/Transdermal penetration in vitro/Analgesia分类
医药卫生引用本文复制引用
赵济,查学志,梅佳华,唐钧泽,薛蕊,周益,杨丽娟,马云淑..罗通定立方液晶凝胶构建与初步药效学考察[J].药学研究,2025,44(7):640-648,9.基金项目
国家自然科学基金项目(No.82174065) （No.82174065）
云南省科技厅重大科技专项计划项目(No.202302AA310031) （No.202302AA310031）
云南省科技厅社会发展专项-重点研发计划项目(No.202303AC100025) （No.202303AC100025）
