State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China.
College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
Phytochem Anal. 2021 Apr;32(2):153-164. doi: 10.1002/pca.2905. Epub 2020 Jan 8.
Dispensing granule, an innovative product of traditional Chinese medicine decoction, is widely practiced in clinic. As a prerequisite to support the clinical medication, quality consistency between dispensing granule and traditional decoction need to be evaluated. Furthermore, a generally applicable strategy for consistency evaluation of dispensing granule is needed.
In this study, we aimed to propose an integrated quality-based strategy to assess consistency between dispensing granule and traditional decoction taking Coptidis Rhizoma (CR) as a case study.
For chemical consistency evaluation, efficacy-related Coptis alkaloids were quantified with high-performance liquid chromatography (HPLC). The "Mean ± 3SD" of analyte contents in traditional decoction was considered as the criterion of consistency. And, as auxiliary analysis, principal component analysis (PCA) was employed for data visualisation. For biological consistency evaluation, two one-side t-tests and 90% confidence intervals of the geometric mean ratio of antibacterial zone diameter and 50% inhibitory concentration (IC ) of α-glucosidase inhibition were calculated. The scope of 80.00% to 125.00% was taken as in vitro bioequivalence interval. It was considered internally consistent with traditional decoction when the chemical and biological indices of dispensing granule fulfilled the preset criteria simultaneously.
Eight out of 20 batches of CR dispensing granule were demonstrated consistent with traditional decoction in chemistry and biological activities.
A generally applicable strategy was recommended that integrates chemical and biological characteristics for consistency evaluation of dispensing granule.
中药配方颗粒是中药汤剂的创新产品，在临床上广泛应用。为了支持临床用药，需要对配方颗粒与传统汤剂的质量一致性进行评价。此外，还需要一种普遍适用的配方颗粒一致性评价策略。
本研究以黄连（CR）为例，旨在提出一种基于综合质量的策略来评估配方颗粒与传统汤剂的一致性。
对于化学一致性评价，采用高效液相色谱法（HPLC）定量测定与疗效相关的黄连生物碱。将传统汤剂中分析物含量的“均值±3SD”视为一致性标准。并且，作为辅助分析，采用主成分分析（PCA）进行数据可视化。对于生物一致性评价，计算了抑菌圈直径和α-葡萄糖苷酶抑制率的几何均数比值的两种单侧 t 检验和 90%置信区间。当 80.00%至 125.00%的范围被视为体外生物等效区间时，认为配方颗粒的化学和生物学指标同时满足预设标准时与传统汤剂具有内在一致性。
20 批 CR 配方颗粒中，有 8 批在化学和生物学活性方面与传统汤剂一致。
推荐了一种普遍适用的策略，该策略将化学和生物学特征集成用于配方颗粒的一致性评价。
