目的 以桂枝茯苓胶囊（Guizhi Fuling Capsules，GFC）为研究对象，探索提取温度、提取时间、料液比等关键工艺参数对醇提液与水提液的物性参数及12个功效物质含量的影响，揭示物性参数与功效物质含量之间的相关性，为工艺优化与质量控制提供依据。方法 采用单因素实验设计，设置不同提取温度（电热套的设定控制温度）、提取时间和料液比等工艺参数，制备相应的醇提液和水提液，并测定各中间体的粒径、多分散指数（polydispersity index，PDI）、ζ电位、电导率、pH值、固体总量和折光率；利用UPLC法对没食子酸、4-羟基苯甲酸、氧化芍药苷、没食子酸乙酯、苯甲酸、1,2,3,4,6-O-五没食子酰葡萄糖、桂皮醛、苦杏仁苷、芍药内酯苷、芍药苷、肉桂酸和丹皮酚12种功效物质进行含量测定，通过正交偏最小二乘法-判别分析（orthogonal partial least squares-discriminant analysis，OPLS-DA）、Pearson相关性分析、灰色关联度分析及线性回归模型分析解析工艺参数-物性参数-功效成分的关联性。结果 工艺参数对GFC醇提液和水提液的物性参数和功效物质均存在一定影响，在醇提工序电热套温度不高于200 ℃，提取时间1.5 h，料液比1∶6～1∶8，水提工序电热套温度200～250℃，提取时间1.5～2.0 h，料液比1∶6～1∶8时，多数功效物质含量较高；OPLS-DA模型、Pearson相关性分析、灰色关联度分析及线性回归模型分析结果表明，不同料液比醇提液的ζ电位、电导率、固体总量和苦杏仁苷含量相关，拟合程度较好（R²＞0.7），不同提取温度水提液的粒径、电导率和肉桂酸含量相关，但拟合效果较差。结论 工艺参数通过调控溶液微环境和成分溶出行为，显著影响提取液的物性参数与功效物质的相关性。电导率、ζ电位和固体总量可作为中药制药过程“量-质”传递规律研究的重要依据。

Objective This study investigated the effects of critical process parameters (CPPs, e.g., extraction temperature, time, and solid-liquid ratio) on the physical properties and the content of 12 effective components in both alcoholic and aqueous extracts of Guizhi Fuling Capsules (GFC, 桂枝茯苓胶囊). The correlations between physical properties and effective components were analyzed to provide a basis for process optimization and quality control. Methods A single-factor experimental design was adopted. Different process parameters such as extraction temperature (set control temperature of electric heating jacket), extraction time and solid-liquid ratio were set to prepare the corresponding alcohol extract and water extract, and the particle size, polydispersion index (PDI), ζ potential, conductivity, pH value, total solid content and refractive indexof each intermediate were determined. The contents of 12 effective components (gallic acid, 4-hydroxybenzoic acid, oxypaeoniflorin, ethyl gallate, benzoic acid, 1,2,3,4,6-O-pentagalloylglucose, cinnamaldehyde, amygdalin, albiflorin, paeoniflorin, cinnamic acid, paeonol) were quantified by UPLC. Correlations among CPPs, physical parameters, and effective components were analyzed via the chemometric analysis, including orthogonal partial least squares-discriminant analysis (OPLS-DA), Pearson correlation, grey relational analysis, and linear regression model analysis. Results The CPPs exert certain influences on the physical parameters and effective components of GFC alcoholic extracts and aqueous extracts. Specifically, for the alcoholic extraction process, when the temperature of the electric heating mantle is controlled at ≤ 200 ℃, with an extraction duration of 1.5 h and a solid-liquid ratio ranging from 1:6 to 1:8; and for the aqueous extraction process, when the electric heating mantle temperature is maintained at 200—250 ℃, extraction time is set to 1.5—2.0 h and the solid-liquid ratio is 1:6—1:8, the contents of most bioactive substances are relatively high. Furthermore, the chemometric analysis results indicated that ζ potential, conductivity, and total solids correlated well with the content of amygdalin in alcoholic extracts under different solid-liquid ratios (well-fitted, R² > 0.7). And in aqueous extracts under different temperatures, particle size and conductivity showed some correlation with cinnamic acid content, but with poor fitting. Conclusion Critical process parameters significantly influence the correlation between physical properties and effective components by modulating the solution microenvironment and dissolution behavior. Conductivity, ζ potential and total solid content can serve as important bases for the study of the “quantity-quality” transfer law in the process of traditional Chinese medicine manufacturing.

R283.6

江苏省基础研究计划——青年基金项目（BK20250552）；江苏省卓越博士后计划（2024ZB119）；中药制药过程控制与智能制造技术全国重点实验室定向课题（SKL2023D02002）