基于药效学评价结合正交设计的复方南星止痛膏改良型新药提取工艺优化研究

Optimization of extraction process for the modified new formulation of Compound Nanxing Zhitong Plaster based on pharmacodynamic evaluation combined with orthogonal design

摘要

目的: 确定并优化复方南星止痛膏改良型新药提取工艺。方法: 采用佐剂性关节炎(adjuvant-induced arthritis,AIA)大鼠模型、冰醋酸致小鼠疼痛模型进行药效学评价,同时对家兔皮肤刺激性进行考察,比较2种提取工艺(FFNX-1:醇提+水提+醇提;FFNX-2:渗漉+醇提)在药效和皮肤安全性方面的差异;再以活性成分(乌头碱、丁香酚等)含量及干膏得率为指标,结合正交实验优化提取参数。结果: FFNX-2(渗漉+醇提)在抑制大鼠足趾肿胀、降低炎症因子及镇痛作用上效果最优,同时能降低家兔的皮肤刺激性,确定为复方南星止痛膏改良型新药的最佳提取工艺路线。结论: 优化后的最佳提取工艺参数为:丁香等六味以4倍量50%乙醇提取3次(每次1 h),生天南星、生川乌以70%乙醇渗漉提取(粒径2~5 mm,浸渍24 h,流速1 mL·min^-1·kg^-1,收集8倍量)。优化后的提取工艺在有效保留关键药效物质的同时,显著降低了潜在毒性风险,为复方南星止痛膏的现代化开发及临床应用提供了科学依据。

Abstract

Objective: To optimize the extraction process for the modified new formulation of Compound Nanxing Zhitong Plaster. Methods: Pharmacological effects were evaluated using adjuvant-induced arthritis rat models and acetic acid-induced writhing mouse models, while skin irritation was tested in rabbits. The differences in efficacy and skin safety between two extraction methods (FFNX-1: ethanol-water-ethanol extraction; FFNX-2: percolation+ethanol extraction) were compared. Active ingredient contents (including aconitine, eugenol, etc.) and dry extract yield were used as indicators to optimize extraction parameters through orthogonal experimental design. Results: FFNX-2 (percolation+ethanol extraction) exhibited optimal anti-swelling, anti-inflammatory and analgesic effects, along with lower skin irritation in rabbits, establishing it as the optimal extraction process for the improved new drug formulation of Compound Nanxing Zhitong Plaster. Conclusion: The optimized extraction parameters were as follows: Six herbs including Caryophylli Flos extracted three times (1 h each) with 4 volumes of 50% ethanol; Arisaematis Rhizoma and Aconiti Radix extracted by percolation with 70% ethanol (particle size 2~5 mm, soaked for 24 h, flow rate 1 mL·min^-1·kg^-1, collecting 8 volumes of effluent). The optimized extraction process effectively retains active components while reducing toxicity risks, providing a scientific basis for the modern development of Compound Nanxing Zhitong Plaster.

关键词

复方南星止痛膏 / 改良型新药 / 药效学 / 正交设计 / 提取工艺 / 乌头碱 / 丁香酚

Key words

Compound Nanxing Zhitong Plaster / improved new formulation / pharmacodynamics / orthogonal design / extraction technology / aconitine / eugenol

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基金资助

江苏省基础研究计划自然科学基金资助项目:前沿引领技术基础研究专项(BK20232014)