乌头类有毒中药常用配伍药对的物质基础研究

【作者】 余成浩；

【导师】 彭成；

【作者基本信息】 成都中医药大学 ， 方剂学， 2006， 博士

【摘要】 目的：研究乌头类有毒中药常用配伍药对的不同配伍比例在不同的配伍环境中，对总生物碱、酯型生物碱、乌头类生物碱各成分及与之配伍中药的相关有效成分(芍药苷、蒽醌类成分、酚类成分)进行含量分析，建立不同配伍关系中有毒或有效成分的化学库，确定乌头类有毒中药毒效反应的物质基础，探讨炮制及配伍规律的科学性和合理性。 方法：采用多指标评价体系评价乌头类有毒中药常用配伍药对的不同配伍比例在水煎液、人工胃液、人工肠液环境中毒效组分及毒效成分的变化，分别采用酸性染料比色法、改良异羟肟酸铁分光光度法测定乌头类总生物碱、酯型生物碱的含量，采用HPLC法测定乌头类生物碱及配伍药味的芍药苷、蒽醌类成分、酚类成分的含量。 结果：1．在川乌配伍(生川乌、制川乌)白芍、草乌(生草乌、制草乌)配伍白芍、附子(生附子、白附片、黑顺片)配伍大黄、附子(生附子、白附片、黑顺片)配伍干姜各配伍组中，总生物碱含量呈现升高趋势、酯型生物碱的含量呈现部分升高或者降低的趋势，为不同配伍关系(配白芍、大黄、干姜)在临床使用的减毒增效科学内涵提供一定的科学依据。 2．乌头配伍白芍 配伍白芍后，不同药味和不同配伍比例间对总生物碱含量影响较小；在人工胃液和人工肠液孵化后，总生物碱含量均有显著下降。可见配伍白芍在总生物碱水平上影响不大，但人工胃、肠液对总生物碱有影响。配伍白芍后，不同药味和不同配伍比例对酯型生物碱含量均有升高；在人工胃液和人工肠液孵化后，生物碱含量均有显著升高。可见配伍白芍在酯型生物碱水平上有影响，以人工胃、肠液对其影响较大。配伍白芍后，不同药味和不同配伍比例的对总双酯型生物碱均略有减低，其中，生品的影响强于制品，随白芍含量升高有下降的趋势；草乌中新乌头碱和次乌头碱的稳定性强于乌头碱，川乌中乌头碱和次乌头碱的稳定性强于新乌头碱；在人工胃液和人工肠液孵化后，双酯型生物碱含量均有显著下降，但各单一生物碱均下降并保持稳定的含量。可见配伍白芍后对生品的影响强于制品，同时双酯型生物碱含量的稳定可能是保证药效的关键。配伍白芍后，不同药味和不同配伍比例对芍药苷含量影响较大。 3．附子配伍大黄 配伍大黄后，不同药味和不同配伍比例间对白附片总生物碱含量影响不同，生品影响不大，炮制品显著升高，在人工胃液和人工肠液孵化后，总生物碱含量显著升高。可见配伍大黄在总生物碱水平上影响与药材含量有关。配伍大黄后，不更多还原

【Abstract】 Objectives: Researching the effect on the contents of total alkaloids、 ester alkaloids、 alkaloids in the aconite root species and the active components(paeoniflorin、AQ、 phenols) in the compatibility of others Chinese drugs and aconite root in the different compatibility ratio and circumstance, ascertaining the material basis of toxic reactions in the aconite root species, establishing the chemi-library of toxic or effective components in the different compatibility relationship, and approaching the sciencity and rationality of compatibility disciplines.Methods: Through different medical materials and different compatibility ratio in the circumstance of decoction、artificial gastric and intestinal juice, applying multi-indexes evaluation system to evaluate the compositions and components of toxicity and potency. Applying acid dye colorimetry and hydroxamic acid iron spectrophotometry to determine total alkaloids and ester alkaloids respectively in the double-drugs compatibility of aconite root species; using HPLC to determine the components of alkaloids in aconite root、 paeoniflorin, AQ and phenols.Results: The content of total alkaloids shows step-up tendency, and the content of ester alkaloids shows step-up or descended tendency in the compatibility of Radix aconiti (CRA、 RAP)and Radix Paeoniae Albae (RPA)、 Radix aconiti kusnezoffii (CRAK、 RAKP)and RPA、 RALP(CRALP、 WPLRA、 BPLRA) and RRR、 RALP(CRALP、 WPLRA、 BPLRA) and Rhizoma Zingiberis (RZ). This study provides scientific basis to some extent for synergy or attenuation of the different compatibility relationship in the clinic application.After compatibility RPA, the change of the contents of total alkaloids in the different medical material and different ratio is very little;However, that content is significantly decreased in artificial gastric juice and artificial intestinal juice. After compatibility RPA, the change of the content of ester alkaloids increases, whether it is in the different medical material and different ratio or in artificial gastric juice and artificial intestinal juice, however, the effect in the artificial gastric or intestinal juice is bigger. After compatibility RPA, the contents of total diester alkaloids is slightly decreased, the decrease in crude material is bigger than prepared materials, with the increase of RPA and has descended tendency; in the direction of medical materials, the stability of MA and HA in RAK is stronger than AC, the stability of AC更多还原