摘要
目的:基于质量源于设计(QbD)理念,优化煅自然铜炮制工艺,并建立煅自然铜X-射线衍射(XRD)指纹图谱。方法:以煅自然铜的安全性、有效性及质量可控性为目标产品质量概况(QTPP),以颜色、硬度、金属光泽、物相组成、重金属及有害元素含量为关键质量属性(CQAs),确定煅制温度、煅制时间、铺置厚度、粒径为关键工艺参数(CPPs)。采用差示热分析法、X-射线衍射法(XRD)及电感耦合等离子体质谱法(ICP-MS)分析煅制温度与煅自然铜CQAs间的关联性。再运用基于指标相关性的指标权重确定法(CRITIC)-熵权法,通过正交试验优选出煅自然铜最佳炮制工艺。采用粉末XRD对按最佳工艺炮制的煅自然铜样品进行物相分析,通过几何拓扑图形叠加建立煅自然铜的平均数图谱和中位数图谱,并进行相似度评价与聚类分析。结果:单因素试验表明,温度升高过程中自然铜物相从FeS_(2)转变成Fe_(7)S_(8),颜色从暗黄色逐渐加深、重金属及有害元素含量降低。优化后的煅自然铜炮制工艺为煅制温度750℃、煅制时间2.5 h、铺置厚度3 cm、粒径0.8~1.2 cm,醋淬1次[自然铜-醋(10:3)]。自然铜煅制后内部结构呈蜂窝状,有利于有效成分的溶出。建立了以10个共有峰为特征指纹信息的13批煅自然铜的XRD指纹图谱;所分析样品XRD指纹图谱的相对峰强的相似度均>0.96,且能有效区分生品及不合格品。结论:温度为影响煅自然铜质量的主要因素,炮制后自然铜有效成分溶出增加,重金属及有害物质含量降低,体现炮制增效减毒的功能,优选出的炮制工艺稳定、可行。建立的煅自然铜XRD指纹图谱可作为煅自然铜质量控制标准之一。
Objective:Based on the concept of quality by design(QbD),the processing process of calcined Pyritum was optimized,and its X-ray diffraction(XRD)fingerprint was established.Methods:The safety,effectiveness and quality controllability of calcined Pyritum were taken as the quality profile(QTPP),the color,hardness,metallic luster,phase composition,the contents of heavy metals and hazardous elements were taken as the critical quality attributes(CQAs),and the calcination temperature,calcination time,paving thickness and particle size were determined as the critical process parameters(CPPs).Differential thermal analysis,X-ray diffraction(XRD)and inductively coupled plasma mass spectrometry(ICP-MS)were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum.Then,based on the criteria importance through intercriteria correlation(CRITIC)-entropy weight method,the optimal processing process of calcined Pyritum was optimized by orthogonal test.Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process,and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures,and similarity evaluation and cluster analysis were carried out.Results:The results of single factor experiments showed that the physical phase of Pyritum changed from FeS_(2)to Fe_(7)S_(8)during the process of temperature increase,the color gradually deepened from dark yellow,and the contents of heavy metals and harmful elements decreased.The optimized processing process of calcined Pyritum was as follows:calcination temperature at 750℃,calcination time of 2.5 h,paving thickness of 3 cm,particle size of 0.8-1.2 cm,vinegar quenching 1 time[Pyritum-vinegar(10∶3)].After calcination,the internal structure of Pyritum was honeycomb-shaped,which was conducive to the dissolution of active ingredients.XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established.The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96,and it could effectively distinguish the raw products and unqualified products.Conclusion:Temperature is the main factor affecting the quality of calcined Pyritum.After processing,the dissolution of the effective components in Pyritum increases,and the contents of heavy metals and harmful substances decrease,reflecting the function of processing to increase efficiency and reduce toxicity.The optimized processing process is stable and feasible,and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.
作者
陈欣
周靖惟
苟海英
钟磊
何天行
费文波
邹佳良
杨玥
曾德雯
陈林
陈鸿平
陈士林
胡媛
刘友平
CHEN Xin;ZHOU Jingwei;GOU Haiying;ZHONG Lei;HE Tianxing;FEI wenbo;ZOU Jialiang;YANG Yue;ZENG Dewen;CHEN Lin;CHEN Hongping;CHEN Shilin;HU Yuan;LIU Youping(State Key Laboratory of Southwestern Traditional Chinese Medicine(TCM)Resources,School of Pharmacy,Chengdu University of TCM,Chengdu 611137,China;Sichuan Neo-green Pharmaceutical Technology Development Co.Ltd.,Pengzhou 611930,China)
出处
《中国实验方剂学杂志》
北大核心
2025年第13期197-205,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家中医药管理局第四次全国中药资源普查项目(GZY-KJS-2018-004,GZY-KJS-2019-001)。
