张晓阳1，侯一哲1，黎 翩2，李 正1，李文龙1*
（1. 天津中医药大学 a. 中药制药工程学院，b. 现代中医药海河实验室，天津 301617；2. 朗天药业（湖北）有限公司，湖北 黄石 435000）
张晓阳，侯一哲，黎翩，等 . 三七总皂苷提取物物理指纹图谱构建及预测方法［J］. 中国粉体技术，2024，30（4）：115-127.
ZHANG X Y， HOU Y Z， LI P， et al. Construction and prediction of physical fingerprints of notoginseng total saponins extracts［J］. China Powder Science and Technology，2024，30（4）：115−127.
DOI：10.13732/j.issn.1008-5548.2024.04.011
收稿日期：2023-10-28，修回日期：2024-05-30，上线日期：2024-06-26。
基金项目：国家自然科学基金项目，编号：82074276；国家重点研发计划项目，编号：2023YFC3504502；现代中医药海河实验室科技计划项目，编号：22HHZYSS00004
第一作者简介：张晓阳（1999—），男，硕士研究生，主要从事中药质量控制技术研究，E-mail：1604424756@qq.com。
通信作者简介：李文龙（1980—），男，副研究员，博士生导师，主要从事中药质量控制技术研究，E-mail： wshlwl@tjutcm. edu. cn.
摘要：【目的】 为了丰富中药质量一致性评价手段，促进新原料的风险评估，提升中药原料的质量控制水平。【方法】以三七总皂苷提取物为研究对象，借鉴中药化学指纹图谱的概念，构建其物理指纹图谱，通过数据驱动的方法对不同批次原料之间的差异进行深入分析并探索关键物理属性参数之间的关系；根据主成分分析和层次聚类分析的结果划分样品类别，在此基础上建立分类模型并筛选出造成样品物理属性质量差异的重要变量；采用近红外光谱技术对不同原料的质量进行快速识别并建立重要物理属性参数的快速预测方法。【结果】 首先清晰地阐明了关键物理属性参数之间的关系，筛选出了对样本分类贡献较大的物理属性参数；建立了能够快速有效鉴别原料差异的分类模型；采用近红外光谱技术对不同原料的质量进行了快速识别并建立了重要物理属性参数的快速预测方法。【结论】 本文中所建方法可以对不同批次三七总皂苷提取物的物理属性质量进行准确分析，能够最大化地从物理属性参数数据中提取有效信息，从而提升药品生产过程中原料的质量控制水平。
关键词：三七总皂苷提取物；物理指纹图谱；数据驱动；近红外光谱
Objective The current research on the quality consistency evaluation of traditional Chinese medicine mainly focuses on the chemical level， and often overlooks the examination of physical quality attributes. In the production process of traditional Chinese medicine formulations， the physical properties of raw materials significantly impact the formulation and molding quality. As a supplement to the evaluation of chemical properties， the construction of physical fingerprints can reflect the overall properties of raw materials， thereby providing data support for the application of design concepts in the quality control research of traditional Chinese medicine raw materials.
Method This study takes the total saponin extract of Panax notoginseng saponins as the research object and evaluates the consistency of samples from different manufacturers from a physical perspective by constructing its physical fingerprint map. A NIR method was developed to address the issue of tedious and time-consuming determination process of physical property parameter，which is not conducive to real-time release during production. This method is used to quickly identify the physical property quality of different raw materials and establish a fast prediction model for important physical property parameters.
Results This method can accurately analyze the physical quality of different batches of Panax ginseng total saponin extracts，maximizing the extraction of effective information from the physical property data and facilitating the selection of raw materials in the production process of formulations. It can be used by companies in the early development stage of process design. In addition， the data analysis method presented in this paper is effective in the process of product development and process optimization， as most results can be represented graphically， allowing production staff without a background in data modelling to easily understand the changing patterns of the data.
Conclusion A NIR method has been developed to address the issue of tedious and time-consuming physical property parameter determination process， which is not conducive to real-time release during production. This method is used to quickly identify the physical property quality of different raw materials and establish a fast prediction model for important physical property parameters. The method developed in this study could accurately analyze the physical quality of different batches of Panax ginseng total saponin extracts， which could maximize the extraction of effective information from the physical property data and facilitate the selection of raw materials in the production process of formulations and could be used by companies in the early development stage of process design. In addition， the data analysis method presented in this paper is effective in the process of product development and process optimization as most of the results can be represented graphically so that production staff without a background in data modelling can easily understand the changing patterns of the data. This method can improve the production efficiency of enterprises and enhance the quality control of traditional Chinese medicine. At the same time， this research idea is not limited to the powder of Panax ginseng total saponin extract， but is also applicable to other raw materials of traditional Chinese medicine， as well as auxiliary materials and other powdered substances.
Keywords：notoginseng total saponins； physical fingerprint； data-driven； near-infrared spectroscopy
［1］LEANE M， PITT K， REYNOLDS G. A proposal for a drug product manufacturing classification system （MCS） for oral solid dosage forms［J］. Pharmaceutical Development & Technology，2015，20（1）：12-21.
［2］张毅，徐冰，孙飞，等. 中药提取物粉末物理指纹谱研究及应用［J］. 中国中药杂志，2016，41（12）：2221-2227. ZHANG Y， XU B， SUN F， et al. Physical fingerprint for quality control of traditional Chinese medicine extract powders［J］.China Journal of Chinese Materia Medica，2016，41（12）：2221-2227.
［3］DAI S Y， XU B， SHI G L， et al. SeDeM expert system for directly compressed tablet formulation： a review and new perspectives［J］. Powder Technology，2018，342：517-527.
［4］毕映燕，李俊江，李季文，等. 基于质量源于设计（QbD）理念的祛寒逐风颗粒制备工艺及其物理指纹图谱研究［J］.中草药，2021，52（19）：5891-5898. BI Y Y， LI J J， LI J W， et al. Study on preparation technology and physical fingerprint of Quhan Zhufeng Granules based on quality by design［J］. Chinese Traditional and Herbal Drugs，2021，52（19）：5891-5898.
［5］罗铮，邓雯，张前亮，等. 当归破壁粉制备工艺优化及物理指纹图谱评价研究［J］. 中草药，2019，50（24）：5980-5987. LUO Z， DENG W， ZHANG Q L， et al. Optimization of preparation process and evaluation of physical fingerprint of Angelicae Sinensis Radix cell wall broken powder［J］. Chinese Traditional and Herbal Drugs，2019，50（24）：5980-5987.
［6］SNICK B V， DHONDT J， PANDELAERE K， et al. A multivariate raw material property database to facilitate drug product development and enable in-silico design of pharmaceutical dry powder processes［J］. International Journal of Pharmaceutics，2018，549（1/2）：415-435.
［7］ESCOTET-ESPINOZA M S， MOGHTADERNEJAD S， SCICOLONE J， et al. Using a material property library to find surrogate materials for pharmaceutical process development［J］. Powder Technology，2018，339：659-676.
［8］BENEDETTI A， KHOO J， SHARMA S， et al. Data analytics on raw material properties to accelerate pharmaceutical drug development［J］. International Journal of Pharmaceutics，2019，563：122-134.
［9］祝明利，张芳语，张瀚，等. 中药大品种制造关键质量属性表征：粉末与颗粒物理属性的苏黄止咳胶囊中间体过程质量控制方法研究［J］. 中国中药杂志，2021，46（7）：1636-1643. ZHU M L， ZHANG F Y， ZHANG H， et al. Critical quality attribute assessment of big brand traditional Chinese medicine：process quality control method of Suhuang Zhike Capsules intermediate based on physical properties of powder and granules［J］. China Journal of Chinese Materia Medica，2021，46（7）：1636-1643.
［10］陈恒晋，杨光，赵立杰，等. 基于粉体特征物理性质的中药饮片分类研究［J］. 中国中药杂志，2021，46（15）：3753-3763. CHEN H J， YANG G， ZHAO L J， et al. Material classification of decoction pieces based on physical properties of powder［J］.China Journal of Chinese Materia Medica，2021，46（15）：3753-3763.
［11］张前亮，罗铮，邓雯，等. 丹参破壁饮片物理属性的质量评价［J］. 中国实验方剂学杂志，2020，26（23）：145-152. ZHANG Q L， LUO Z， DENG W， et al. Quality evaluation of physical properties of ultrafine granular powder of Salviae miltiorrhizae radix et rhizoma［J］. Chinese Journal of Experimental Traditional Medical Formulae，2020，26（23）：145-152.
［12］曹君杰，徐冰，戴胜云，等. iTCM中药口服固体制剂原辅料物性数据库的构建及应用［J］. 中草药，2021，52（17）：5166-5175. CAO J J， XU B， DAI S Y， et al. Construction and application of iTCM material database for pharmaceutical excipients of Chinese medicine oral solid dosage forms［J］. Chinese Traditional and Herbal Drugs，2021，52（17）：5166-5175.
［13］胡庆轩，郑怀玉，林文娟，等. 有机粉体流动性的测定［J］. 中国粉体技术，1999（5）：11-14. HU Q X， ZHENG H Y， LIN W J， et al. Determination of fluidity of organic powder［J］. China Powder Science and Tech⁃nology，1999（5）：11-14.
［14］张鹏. 卡尔指数法在评价煤粉粉体特性中的应用［J］. 中国粉体技术，2000（5）：33-36. ZHANG P. Application of Carr index method in comprehensive evaluating properties of coal powder［J］. China PowderScience and Technology，2000（5）：33-36.
［15］SCHOLTZ J C， STEENEKAMP J H， HAMMAN J H， et al. The SeDeM expert diagram system： its performance and predictability in direct compressible formulations containing novel excipients and different types of active ingredients［J］. Powder Technology，2017，312：222-236.
［16］ISAAC N， ANNA N， MARC S， et al. Optimization of the cohesion index in the SeDeM diagram expert system and application of SeDeM diagram： an improved methodology to determine the cohesion index［J］. PLoS One，2018，13（9）：0203846.
［17］李延年，伍振峰，尚悦，等 . 基于浸膏物理指纹谱评价不同干燥方式对浸膏粉体性质的影响［J］. 中草药，2018，49（10）：2372-2377. LI Y N， WU Z F， SHANG Y， et al. Effect on different drying methods on powder properties of extraction paste based on physical fingerprint of extract［J］. Chinese Traditional and Herbal Drugs，2018，49（10）：2372-2377.
［18］张煜皓，王雅雯，宿军慧，等. 中药粉体物理指纹图谱研究进展［J］. 分析测试学报，2021，40（1）：139-148. ZHANG Y H， WANG Y W， SU J H， et al. Physical fingerprint of traditional Chinese medicine powders： a review［J］. Journal of Instrumental Analysis，2021，40（1）：139-148.
［19］RAYMOND C R， PAUL J S， MARIAN E Q. Handbook of pharmaceutical excipients［M］. Sixth edition. London： the Pharmaceutical Press，2009.
［20］GAO S M， LIU J S， WANG M， et al. Quantitative and HPLC fingerprint analysis combined with chemometrics for quality evaluation of codonopsis radix processed with different methods［J］. Chinese Herbal Medicines，2019，11（2）：160-168.
［21］邹纯才，鄢海燕. 我国中药色谱指纹图谱相似度评价方法30年（1988—2017年）研究进展与展望［J］. 中国中药杂志，2018，43（10）：1969-1977. ZOU C C， YAN H Y. Research progress on chromatographic fingerprint similarity evaluation method for traditional Chinese medicine in the past 30 years （1988—2017） and its prospect［J］. China Journal of Chinese Materia Medica，2018，43（10）：1969-1977.
［22］侯文，刘宏胜，王树森，等 . 基于 HPLC指纹图谱和多成分同时测定的护肝剂质量评价研究［J］. 中草药，2018，49（24）：5830-5835. HOU W， LIU H S， WANG S S， et al. Quality evaluation of Liver-protection Agent based on HPLC fingerprint and simultaneous determinations of multiple components［J］. Chinese Traditional and Herbal Drugs，2018，49（24）：5830-5835.
［23］LEE G J， LEE J H， PARK J H， et al. Assessment of chemical equivalence in herbal materials using chromatographic fingerprints by combination of three similarity indices and three-dimensional kernel density estimation［J］. Analytica Chimica Acta，2018，1037：220-229.
［24］JAIN A K， DUIN R P W， MAO J C. Statistical pattern recognition： a review［J］. IEEE Transactions on Pattern Analysis and Machine Intelligence，2000，22（1）：4-37.
［25］BOCCARD J， RUTLEDGE D N. A consensus orthogonal partial least squares discriminant analysis （OPLS-DA） strategy for multiblock omics data fusion［J］. Analytica Chimica Acta，2013，769（6）：30-39.
［26］张坤峰，王政，曹君杰，等. 中药口服固体制剂原辅料近红外光谱数据库的构建及应用［J］. 分析测试学报，2021，40（1）：1-9. ZHANG K F， WANG Z， CAO J J， et al. Establishment and application of a near lnfrared spectral database for pharmaceutica excipients of Chinese medicine oral solid dosage forms［J］. Journal of Instrumental Analysis，2021，40（1）：1-9.
