黄芩—柴胡“药对”配伍的药学及药代动力学研究
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摘要
目的:揭示临床配伍应用能显著提高药物疗效的经典“药对”黄芩-柴胡的药效物质基础,为中医临床辨证用药时采用“药对”合理组方配伍提供现代医药学的理论依据。
方法:对黄芩、柴胡相关文献进行查阅,了解黄芩、柴胡研究概况,为实验研究奠定基础;采用高效液相技术建立测定各供试溶液中黄芩苷和柴胡皂苷等相关药效成分含量的测定方法;参考临床用药方法,对提取溶媒、用量、浸泡时间、提取次数等进行四因素三水平正交设计实验,优选出供试药材最佳提取工艺;采用高效液相技术建立起受试动物血浆中药效成分-黄芩苷含量的方法;对体内实验所得数据,采用DAS2.0专业处理软件进行药代动力学统计和分析。
结果:药学实验发现,考察提取溶剂对黄芩-柴胡“药对”配伍中药效成分提出率的影响中,黄芩-柴胡“药对”配伍后黄芩苷的提出率比药材单独提取要高,进一步证实了混煎增溶理论,从化学成分研究的角度说明了中药配伍用药的科学性和合理性,供试药材最佳提取工艺为8倍量70%乙醇,加热回流提取2次,每次1h,黄芩柴胡“药对”不同比例的配伍之间差异不大,黄芩-柴胡“药对”不同比例配伍前后对主要药效学成分黄芩苷的含量影响亦不大,但黄芩苷峰前的一个吸收峰明显增大,推测配伍应用会增强其他组分的提出;药代动力学实验发现,黄芩-柴胡1:1“药对”配伍后,黄芩苷体内吸收加快,吸收峰前移0.34h,说明黄芩-柴胡1:1“药对”配伍提高了黄芩苷成分的吸收速率,使得黄芩苷在体内发挥药效时间提前,另外药对配伍后黄芩苷吸收出现的体内二次达峰使黄芩苷在体内的滞留时间更长,黄芩-柴胡1:2“药对”配伍后黄芩苷体内吸收趋势和黄芩-柴胡1:1“药对”相近,因此黄芩-柴胡“药对”配伍方式不仅促进了大鼠黄芩苷的吸收而且使其发挥药效作用的时间延长。
结论:通过对黄芩-柴胡“药对”系统科学的药学及药代动力学研究,确定该药对的最佳提取方法、提取工艺和配伍方式,从而使黄芩-柴胡“药对”配伍的研究达到科学准确,完善统一,为中药药对配伍的研究和开发奠定坚实的基础。
Objective: To analyze effective substance of Radix Scutellare and Radix Bupleuri in compatibility enhancing and changing the treatment that was proved to enhance drug effect by tcm clinical practice and pharmacological effect, in order to provide theoretical basis of modern medicine science for reasonable combination of tcm doctors prescribing medicine.
Methods: Through consulting the related literature and learning about the research survey of Scutellaria and Bupleurum to lay a foundation for the experiments; high performance liquid chromatographic was used to determine the contents of baicalin and saikosaponin in sample solution;make reference to the clinical use of the drug, take extracting solvent, dosage, soaking time and extracting times by the four factors and three levels orthogonal test L9(3~4),and choose the optimum extraction process of tested plants. And baicalin contents in the plasma were measured by high performance liquid chromatography; the parameters of pharmacokinetics were calculated by DAS2.0 software.
Results: The influence of extraction solvent on extraction ratio of medical components from Radix Scutellare and Radix Bupleuri in compatibility was studied in pharmacy experiment, and with baicalin as indicators, the alcohol extraction process of the drug pair was better than the extraction. The experimental results showed that combined decoction raised the solubilization capacity obviously, and the rationality and validity of the Chinese medicine drug pair are verified in the view of chemical composition. The best extracting condition was with 8times amount of 70% ethanol to operate heating circumfluence, for 3 times and 1h per time. The results showed that different compatibilities of Radix Bupleuri and Radix Scutellariae had small difference, and different compatibilities also had little effect on the content of baicalin, but the peak area of one absorption peak in front of baicalin increased evidently, so combined Radix Scutellare and Radix Bupleuri could enhance the extraction rate of the other constituents except baicalin;In pharmacokinetics study, after adopting 1:1drug -pair of Radix Bupleuri and Radix Scutellariae,baicalin was absorbed more rapidly in vivo than Radix Scutellariae,and the absorption peak of baicalin was moved forward by 0.34h, so the 1:1 drug -pair of Radix Bupleuri and Radix Scutellariae improved the rate to absorpt baicalin, making medicine efficacy of baicalin time advance, in addition, the secondry absorption peak of baicalin extended the retention time in rat in vivo after adopting the coupled drug dispensing of Scutellare– Bupleuri, and the absorption trend of baicalin in vivo of the 1:2 coupled drug dispensing of Scutellare– Bupleuri was similar with the 1:1 coupled drug dispensing, so the compatibility of Scutellare– Bupleuri not only promoted the absorption of baicalin in rat in vivo but also prolonged medicine efficacy time of it.
Conclusion: By researching pharmaceutical and pharmacokinetic research on drug pair of Scutellaria and Bupleurum based on system science, determine the optimal extraction method,the best extraction technology and compatibility way, and the study on the coupled drug of Scutellaria and Bupleurum can be scientifically and perfectly ,thereby, we can establish solid foundation for the research and development of the Chinese medicine drug pair.
方法:对黄芩、柴胡相关文献进行查阅,了解黄芩、柴胡研究概况,为实验研究奠定基础;采用高效液相技术建立测定各供试溶液中黄芩苷和柴胡皂苷等相关药效成分含量的测定方法;参考临床用药方法,对提取溶媒、用量、浸泡时间、提取次数等进行四因素三水平正交设计实验,优选出供试药材最佳提取工艺;采用高效液相技术建立起受试动物血浆中药效成分-黄芩苷含量的方法;对体内实验所得数据,采用DAS2.0专业处理软件进行药代动力学统计和分析。
结果:药学实验发现,考察提取溶剂对黄芩-柴胡“药对”配伍中药效成分提出率的影响中,黄芩-柴胡“药对”配伍后黄芩苷的提出率比药材单独提取要高,进一步证实了混煎增溶理论,从化学成分研究的角度说明了中药配伍用药的科学性和合理性,供试药材最佳提取工艺为8倍量70%乙醇,加热回流提取2次,每次1h,黄芩柴胡“药对”不同比例的配伍之间差异不大,黄芩-柴胡“药对”不同比例配伍前后对主要药效学成分黄芩苷的含量影响亦不大,但黄芩苷峰前的一个吸收峰明显增大,推测配伍应用会增强其他组分的提出;药代动力学实验发现,黄芩-柴胡1:1“药对”配伍后,黄芩苷体内吸收加快,吸收峰前移0.34h,说明黄芩-柴胡1:1“药对”配伍提高了黄芩苷成分的吸收速率,使得黄芩苷在体内发挥药效时间提前,另外药对配伍后黄芩苷吸收出现的体内二次达峰使黄芩苷在体内的滞留时间更长,黄芩-柴胡1:2“药对”配伍后黄芩苷体内吸收趋势和黄芩-柴胡1:1“药对”相近,因此黄芩-柴胡“药对”配伍方式不仅促进了大鼠黄芩苷的吸收而且使其发挥药效作用的时间延长。
结论:通过对黄芩-柴胡“药对”系统科学的药学及药代动力学研究,确定该药对的最佳提取方法、提取工艺和配伍方式,从而使黄芩-柴胡“药对”配伍的研究达到科学准确,完善统一,为中药药对配伍的研究和开发奠定坚实的基础。
Objective: To analyze effective substance of Radix Scutellare and Radix Bupleuri in compatibility enhancing and changing the treatment that was proved to enhance drug effect by tcm clinical practice and pharmacological effect, in order to provide theoretical basis of modern medicine science for reasonable combination of tcm doctors prescribing medicine.
Methods: Through consulting the related literature and learning about the research survey of Scutellaria and Bupleurum to lay a foundation for the experiments; high performance liquid chromatographic was used to determine the contents of baicalin and saikosaponin in sample solution;make reference to the clinical use of the drug, take extracting solvent, dosage, soaking time and extracting times by the four factors and three levels orthogonal test L9(3~4),and choose the optimum extraction process of tested plants. And baicalin contents in the plasma were measured by high performance liquid chromatography; the parameters of pharmacokinetics were calculated by DAS2.0 software.
Results: The influence of extraction solvent on extraction ratio of medical components from Radix Scutellare and Radix Bupleuri in compatibility was studied in pharmacy experiment, and with baicalin as indicators, the alcohol extraction process of the drug pair was better than the extraction. The experimental results showed that combined decoction raised the solubilization capacity obviously, and the rationality and validity of the Chinese medicine drug pair are verified in the view of chemical composition. The best extracting condition was with 8times amount of 70% ethanol to operate heating circumfluence, for 3 times and 1h per time. The results showed that different compatibilities of Radix Bupleuri and Radix Scutellariae had small difference, and different compatibilities also had little effect on the content of baicalin, but the peak area of one absorption peak in front of baicalin increased evidently, so combined Radix Scutellare and Radix Bupleuri could enhance the extraction rate of the other constituents except baicalin;In pharmacokinetics study, after adopting 1:1drug -pair of Radix Bupleuri and Radix Scutellariae,baicalin was absorbed more rapidly in vivo than Radix Scutellariae,and the absorption peak of baicalin was moved forward by 0.34h, so the 1:1 drug -pair of Radix Bupleuri and Radix Scutellariae improved the rate to absorpt baicalin, making medicine efficacy of baicalin time advance, in addition, the secondry absorption peak of baicalin extended the retention time in rat in vivo after adopting the coupled drug dispensing of Scutellare– Bupleuri, and the absorption trend of baicalin in vivo of the 1:2 coupled drug dispensing of Scutellare– Bupleuri was similar with the 1:1 coupled drug dispensing, so the compatibility of Scutellare– Bupleuri not only promoted the absorption of baicalin in rat in vivo but also prolonged medicine efficacy time of it.
Conclusion: By researching pharmaceutical and pharmacokinetic research on drug pair of Scutellaria and Bupleurum based on system science, determine the optimal extraction method,the best extraction technology and compatibility way, and the study on the coupled drug of Scutellaria and Bupleurum can be scientifically and perfectly ,thereby, we can establish solid foundation for the research and development of the Chinese medicine drug pair.
引文
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