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Abstract
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Protocol
Results
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Medicine

基于CRITIC结合Box-Behnken响应面法的铁邦岀与赞坝加工工艺优化

Published: May 12, 2023
doi:
10.3791/65139
, , , , , ,
1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy,Chengdu University of Traditional Chinese Medicine, 2School of Ethnic Medicine,Chengdu University of Traditional Chinese Medicine

Summary

本协议描述了一种使用CRITIC结合Box-Behnken反应面法的Zanba炒铁棒净的高效和标准的解毒处理方法。

Abstract

乌头摆的干根，中文称为铁棒翠（TBC），是最著名的藏药之一。它是中国西北地区广泛使用的草药。然而，由于TBC的强烈毒性以及其治疗剂量和毒性剂量相似，发生了许多中毒病例。因此，寻找一种安全有效的方法来降低其毒性是一项紧迫的任务。翻阅藏药典籍，《青海省藏药加工规范（2010）》中记载了TBC炖炒的加工方法。但是，具体的加工参数尚不清楚。因此，本研究旨在优化和规范赞巴炒TBC的加工工艺。

首先，对TBC切片厚度、Zanba用量、加工温度和时间4个因素进行单因素试验。以赞巴炒TBC中单酯和二酯生物碱含量为指标，采用CRITIC结合Box-Behnken响应面法优化赞巴炒TBC的加工工艺。赞巴炒TBC的优化加工条件为TBC切片厚度为2 cm，赞巴是TBC的3倍，加工温度为125 °C，翻炒60 min。本研究确定了赞巴炒TBC使用的优化和标准加工条件，从而为赞巴炒TBC的安全临床使用和工业化生产提供了实验依据。

Introduction

乌头摆布希和黄头的干根，最著名的藏药之一，在中国1，2中被称为铁棒翠（TBC）。TBC的干燥根有助于驱寒和风，减轻疼痛和镇静休克。记录在《中华人民共和国卫生部药品标准（藏药）》第一卷中，其中指出TBC的干根通常用于治疗类风湿性关节炎，跌打损伤和其他感冒疾病3。但TBC的临床治疗剂量与其毒性剂量相似，由于使用不当，中毒或死亡事件屡见不鲜有报道4。因此，降低TBC的毒性，保持疗效成为多年来的研究热点。

在藏药中，加工是减轻TBC毒性的最有效方法之一。根据《青海省藏药加工规范（2010）》，原药材（待定）放入铁锅中，与赞巴一起炒至赞巴变黄，取出赞巴，空气晒干5，6。然而，没有具体的工艺参数记录，这使得控制加工技术和Zanba炒TBC的质量变得困难。CRITIC法是一种客观的权重方法，可以避免模糊化和主观性，增强称重的客观性7.Box-Behnken响应面法可以通过多项式拟合8直接反映各因子之间的相互作用。Box-Behnken响应面和CRITIC方法的组合通常用于优化处理技术，以获得优化的处理协议9，10。本文以单酯-二萜类生物碱（MDA）（苯甲酰乌头碱）和两种二酯-二萜类生物碱（DDAs）（乌头碱、3-脱氧乌头碱）为评价指标。采用CRITIC结合Box-Behnken响应面法优化赞巴炒TBC加工工艺，建立临床安全使用标准加工方法。

Protocol

采用CRITIC结合Box-Behnken响应面法对赞巴炒TBC加工方法进行了优化和标准化。在此过程中，苯甲酰乌头碱、乌头碱和3-脱氧乌头碱用作评价指标。 1. 样品溶液制备 制备对照品储备溶液。在电子分析天平上精确称取9.94 mg苯甲酰乌头碱、8.49 mg乌头碱和6.25 mg3-脱氧乌头碱（材料表），并将它们放入10 mL容量瓶中。然后，加入0.05%盐酸甲醇溶液溶解固体?…

Representative Results

在这项研究中，使用的洗脱梯度对Zanba-炒-炒TBC中的三种指数组分具有良好的分辨率（图1），这是在重复调试后确定的。三霸炒TBC中的3种指标组分在特定浓度范围内具有良好的线性关系（表2）。炒TBC的精密度（表5）、稳定性（表6）、重复性（表7）和样品回收率（表8）均在中国药典（2020年第4卷）22规定?…

Discussion

TBC是一种重要的藏药，具有祛寒止痛的作用。数千年来，它在中国主要用于治疗创伤性损伤和风湿性关节痛24，25，26。二萜类生物碱是TBC 27，28，29的活性和毒性成分。TBC的乌头生物碱的主要毒性作用是神经毒性、心脏毒性和胃肠道毒性30<s…

Disclosures

The authors have nothing to disclose.

Acknowledgements

这项工作得到了国家自然科学基金（第82130113号）、中国博士后科学基金（编号：2021MD703800）、四川省科技厅青年科学基金（编号：2022NSFSC1449）和成都中医药大学“杏林学者”研究推进计划（No.BSH2021009）。

Materials

3-Deoxyaconitine Chengdu Desite Biotechnology Co., Ltd. DST221109-033
Aconitine Chengdu Desite Biotechnology Co., Ltd. DSTDW000602
Ammonium acetate Tianjin Kermel Chemical Reagent Co., Ltd Chromatographic grade
Benzoylaconitine Chengdu Desite Biotechnology Co., Ltd. DSTDB005502
Design-Expert software Stat-Ease, Inc., Minneapolis, MN, USA version 13.0
Electronic analytical balance Shanghai Liangping Instruments Co., Ltd. FA1004
High performance liquid chromatography SHIMADZU Co., Ltd. LC-20A
High-speed smashing machine Beijing Zhongxing Weiye Instrument Co., Ltd. FW-100
Millipore filter Tianjin Jinteng Experimental Equipment Co., Ltd φ13 0.22 Nylon66
stir-Fry machine Changzhou Maisi Machinery Co., Ltd Type 5
Tiebangchui Gannan Baicao Biotechnology Development Co., Ltd 20211012
Ultra pure water systemic RephiLe Bioscience, Ltd. Genie G
Ultrasonic cleansing machine Ningbo Xinyi Ultrasonic Equipment Co., Ltd SB2200
Zanba 27 Chuanzang Road, Ganzi County –
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Tags

TiebangchuiZanbaProcessing TechnologyOptimizationBox-Behnken Response Surface MethodCRITIC MethodTibetan MedicineDetoxificationEfficacyPharmacological Evaluation

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Li, S., Yu, L., Li, C., Wang, N., Lai, X., Liu, Y., Zhang, Y. Optimization of Processing Technology for Tiebangchui with Zanba Based on CRITIC Combined with Box-Behnken Response Surface Method. J. Vis. Exp. (195), e65139, doi:10.3791/65139 (2023).
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