基于指纹图谱和药效评价的丁半方不同剂型一致性研究

Consistency of Different Dosage Forms of Dingban Formula Based on Fingerprint and Pharmacodynamic Evaluation

目的:基于指纹图谱和药效评价丁半合剂和丁半颗粒二者在药效质量方面的一致性,并探讨丁半清热方的作用机制。方法:建立12批丁半制剂的指纹图谱,确定共有峰及其来源归属,并进行数据分析和相似度评价;建立干酵母混悬液致大鼠发热模型,给药7 d,记录体温,观察阿司匹林组、丁半合剂高剂量组、丁半合剂低剂量组、丁半颗粒高剂量组和丁半颗粒低剂量组对发热大鼠的解热作用;建立二甲苯致小鼠耳郭肿胀模型,观察阿司匹林组、丁半合剂高剂量组、丁半合剂低剂量组、丁半颗粒高剂量组和丁半颗粒低剂量组对小鼠耳郭肿胀度的影响。酶联免疫吸附试验法(ELISA)测定各组发热大鼠下丘脑中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的含量。结果:12批制剂指纹图谱中确定了13个共有峰,丁半合剂和丁半颗粒在指纹图谱上具有一致性,表现出相同的物质基础。与模型组比较,丁半合剂和丁半颗粒均能降低干酵母所致发热大鼠的直肠温度,差异有统计学意义(P<0.05);与对照组比较,丁半颗粒高剂量组对二甲苯致小鼠耳郭肿胀抑制率较高,差异有统计学意义(P<0.05)。丁半合剂和丁半颗粒能抑制发热大鼠下丘脑中TNF-α和IL-1β含量的升高。结论:丁半合剂和丁半颗粒在指纹图谱和药效作用方面具有一致性,二者均有的解热抗炎作用,可能是通过抑制模型大鼠下丘脑TNF-α、IL-1β含量的升高而发挥解热作用。

Objective:To evaluate the consistency in pharmacological quality between Dingban Mixture and Dingban Granules based on fingerprint and pharmacodynamic evaluation and to explore the mechanism of action of Dingban Qingre Formula.Methods:Fingerprint profiles of 12 batches of Dingban preparations were established to identify common peaks and their attributions,followed by data analysis and similarity evaluation.A dry yeast suspension was used to induce fever in rats,with medication administered for 7 days while recording body temperature.The antipyretic effects of aspirin,high-and low-dose Dingban Mixture,and high-and low-dose Dingban Granules were observed in febrile rats.A xylene-induced ear swelling model was also established in mice to assess the effects of aspirin,high-and low-dose Dingban Mixture,and high-and low-dose Dingban Granules on ear swelling.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)in the hypothalamus of febrile rats.Results:The fingerprint analysis identified 13 common peaks across the 12 batches,demonstrating consistency between Dingban Mixture and Dingban Granules with the same material basis.Compared to the model group,both Dingban Mixture and Dingban Granules significantly reduced rectal temperature in febrile rats(P<0.05).The high-dose Dingban Granules group showed a significantly higher inhibition rate of ear swelling than the control group in the xylene-induced mouse model(P<0.05).Both Dingban Mixture and Dingban Granules inhibited the increase of TNF-αand IL-1βlevels in the hypothalamus of febrile rats.Conclusion:Dingban Mixture and Dingban Granules exhibit consistency in fingerprint and pharmacological effects,both demonstrating antipyretic and anti-inflammatory actions.These effects may be mediated through the inhibition of TNF-αand IL-1βelevation in the hypothalamus of the model rats.