目的 制备四逆汤分散片（Sini Decoction dispersible tablets，SDDT），并阐明其药动学行为。方法 采用粉末直接压片法进行SDDT的制备。以崩解时限为评价指标，采用正交设计优化制剂处方。运用“中药色谱指纹图谱相似度评价系统”对10批SDDT与10批四逆汤汤剂（Sini Decoction Decoction，SDD）进行相似度评价。以UPLC-MS/MS法测定大鼠血浆中9种四逆汤指标成分（苯甲酰次乌头原碱、苯甲酰新乌头原碱、苯甲酰乌头原碱、次乌头碱、新乌头碱、乌头碱、6-姜酚、甘草苷、甘草酸铵），以SDD为参比，考察SDDT的药动学特征。结果 SDDT最优处方中四逆汤浸膏粉、交联聚乙烯吡咯烷酮（PVPP）、低取代羟丙基纤维素（L-HPC）、甘露醇与硬脂酸镁的质量比为50.0∶5.0∶5.0∶38.5∶1.5。建立了10批SDD和10批SDDT的UPLC指纹图谱，各样品指纹图谱与对照指纹图谱的相似度均在0.9以上，表明2种剂型组间与组内指标成分的差异均较小。成功建立了可同时测定血浆中9种指标成分的UPLC-MS/MS分析方法，该方法准确、专属性好、灵敏度高。药动学结果表明，与SDD相比，SDDT主要指标成分苯甲酰次乌头原碱和6-姜酚的达峰时间（T_max）提前（P＜0.05），苯甲酰次乌头原碱、6-姜酚、甘草苷的药-时曲线下面积（AUC_0～t和AUC_0～∞）显著提高（P＜0.05、0.001），苯甲酰次乌头原碱和苯甲酰新乌头原碱的峰浓度（C_max）显著提高（P＜0.01）。结论 成功制备了SDDT，且处方工艺稳定，成品中指标成分的波动较小；相较于汤剂，分散片提高了方中指标成分的体内吸收速度与程度。

Objective To prepare Sini Decoction dispersible tablets (四逆汤分散片, SDDT) and elucidate their pharmacokinetic properties. Methods SDDT were prepared using a powder direct compression method. An orthogonal design experiment was conducted to optimize the formulation, focusing on disintegration time as the evaluation criterion. The similarity between 10 batches of SDDT and 10 batches of SDD was assessed using the “Similarity Evaluation Software of Chromatographic Fingerprint of Traditional Chinese Medicine”. The pharmacokinetic characteristics of SDDT were investigated by determining the nine indicators in rat plasma using UPLC-MS/MS, including benzoylhypaconine, benzoylmesaconine, benzoylaconine, hypaconitine, mesaconitine, aconitine, 6-gingerol, liquiritin, ammonium glycyrrhizinate, with SDD as the reference. Results The optimal formulation for the SDDT was found to have a mass ratio of Sini Decoction extract, PVPP, L-HPC, mannitol, and magnesium stearate of 50.0:5.0:5.0:38.5:1.5. The UPLC fingerprints of 10 batches of SDD and 10 batches of SDDT were established. The similarity of the fingerprints of each sample to the reference fingerprint was above 0.9, indicating that there were minimal differences in the target components between two dosage forms and within dosage form groups. A highly accurate, specific, and sensitive UPLC-MS/MS method was successfully developed for simultaneous determination of nine active ingredients in plasma. Pharmacokinetic analysis revealed that, compared to SDD, the time to peak blood concentration (T_max) for benzoylhypaconine and 6-gingerol of SDDT was significantly reduced (P < 0.05). Additionally, the AUC_0—t and AUC_0—∞ for benzoylhypaconine, 6-gingerol and liquiritin was significantly increased (P < 0.05, 0.001), and the C_max for benzoylhypaconine and benzoylmesaconine was also significantly higher in the dispersible tablets (P < 0.01). Conclusion SDDT were successfully prepared with a stable process and minimal fluctuation in indicator components. Compared to the decoction, the dispersible tablets exhibited improved in vivo absorption rates and extent for the active components.

R283.6

国家自然科学基金资助项目（82074027）;浙江省自然科学基金资助项目（LZ21H280001）;浙江中医药大学附属医院科研专项（2022FSYYZZ31）;温州市基础性科研项目（Y20240033）