星点设计-效应面法优化肝素钠肌醇烟酸酯乳膏处方配比

Optimization of formulation of Heparin and Inositol Nicotinate Cream by central composite design-response surface method

目的通过星点设计-效面优化法,考察肝素钠肌醇烟酸酯乳膏中主药最佳配比。方法选用预防冻伤小鼠足肿胀实验和预防冻伤大鼠局部激光多普勒血流灌注量实验作为药效筛选模型,以肝素钠、肌醇烟酸酯和促透剂氮酮为考察因素,以足肿胀抑制率和血流灌注量为药效评价指标,采用星点设计(Design-Expert 7.0软件)对肝素钠、肌醇烟酸酯和促透剂氮酮进行多因素多水平配伍实验设计,对实验结果进行数学模型预测,根据二项式拟合方程绘制出的因素对指标影响趋势的二维等高线和三维效应面图,选择最佳配伍比例组合。结果星点设计-效应面法结果表明,肝素钠、肌醇烟酸酯和氮酮均有一定的协同作用,试验优选处方药物的配比为:肝素钠8000 U、肌醇烟酸酯200 mg和氮酮600 mg。结论此方法简便易行,预测性良好,提高了试验精度,为提高组合药物的临床有效性提供科学方法和实验依据。

Objective To optimize formulation of Heparin and Inositol Nicotinate Cream by central composite designresponse surface method. Methods The model of paw edema of mice and the blood flow of rats measured by laser Doppler flowmetry （LDF） were chosen as the pharmacodynamic screening index. With the amount of Heparin, Inositol Nicotinate and penetration enhancers ozone were as independent variables, the swelling inhibition rate and the blood perfnsion were as the comprehensive pharmaeodynamic index. Design-Expert 7.0 software was used for the experimental value, and response surface methodology was used to optimize the Heparin, Inositol Nicotinate and ozone using central composite design-response surface method. The prediction was carried out through comparing the observed and predicted with the two-dimension overlaying contour and the three-dimension response surfaces. Results Heparin, Inositol Nicotinate and Azone were proved to have synergistic effectsby central composite design-response surface method. Optimal formulaiton was as following： Heparin 8000 U, Inositol Nicotinate 200 mg and Azone 600 mg. Conclusion Central composite design-response surface methodology is convenient and highly predictive in optimizing formulation of Heparin and Inositol Nicotinate Cream, which can be offered in the scientific methods and experimentation.