麻杏石甘汤药效物质基础研究及新药研制
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摘要
麻杏石甘汤出自汉代张仲景的《伤寒论》,由麻黄、苦杏仁、甘草和石膏四味药组成。具有辛凉宣肺、止咳平喘的功效。通过对麻杏石甘汤的配伍规律和药效物质基础研究,揭示方剂配伍的科学性和作用机制,为研制新型中药制剂提供理论依据。
麻杏石甘汤四味药不同配伍后,和单煎药液相比,主要有效成分麻黄碱、苦杏仁苷和甘草酸的含量都降低,石膏的溶出量有所增加,但影响不显著。
在麻杏石甘汤共煎药液、甘草单煎药液以及有效部位组合药液中,几乎没有检测到甘草次酸的存在,这说明,甘草酸主要是经胃酸或肝中β-葡萄糖醛酸酶作用分解形成甘草次酸,从而产生了解毒,抗炎,镇咳等药理作用。
β2激动剂筛选实验表明,含有麻黄的配伍都有平喘活性,麻黄和甘草的组合活性更强。这表明,麻杏石甘汤的平喘机制应该是通过和β2受体活性部位结合,改变了受体的构象,受体被激活,使得支气管平滑肌松弛,减轻了气道水肿,抑制了炎症细胞等,有利于缓解和消除喘息。
有效部位提取物组方对致喘豚鼠的平喘实验表明,和对照组比较,原方剂和处方5平喘效果有显著性,其它处方无显著性。通过HPLC分析可知,伪麻黄碱和甘草黄酮等可能在平喘机制中起到协同作用。原方剂和处方5也有明显的镇咳和祛痰活性,但是,对肿瘤细胞没有明显的抑制作用。
根据麻杏石甘汤临床用药的特点,将其开发成为配方颗粒新型制剂,对提取工艺进行了优化,并制定了配方颗粒的质量标准。满足临床辩证论治,随症加减的需要,有利于临床医师灵活组方和患者服用。
通过工艺优化,提取得到有效部位,在药效学研究的基础上,研制开发了中药新药喘咳宁滴丸,优化了滴丸的成型工艺并制定了滴丸的质量标准。
Maxingshigan Decoction was recorded in《Treatise on Febrile Diseases》by Zhang zhong-jing in Han Dynasty, which was composed of ephedra、bitter apricot kernel、prepared licorice root and gypsum. It had the effects of clearing lung-heat and relieving cough and ashma and was often used to treat acute and chronic bronchitis、bronchial asthma and so on. In order to clarify the science and mechanism of prescription compatibility ,to give scientific evidence for exploiting new-styly product of Chinese traditional medicine,the compatible regulation and therapeutic basis were researched.
After different compatibility of four drugs,the contents of ephedrine、amygdalin and glycyrrhizinic acid were reduced,and the content of calcium sulphate was slightly increased in decoction compared with every single decoction.
Glycyrrhetic acid was not detected in the Maxingshigan Decoction、licorice root decoction and component compatibility of effective substance , this showed that glycyrrhizic acid was decomposed to generate glycyrrhetic acid by gastric acid in the stomach orβ-glucuronidase in the liver ,which contributed to detoxication、anti-inflammatory and preventing cough.
The experiment ofβ2 agonist screening showed that compatibilities with ephedra had the activity of relieving asthma. This suggested that the mechanism of alleviating asthma was that when drugs were combined with the active part ofβ2 receptor ,the conformation of receptor was changed and receptor was activated,spasm of bronchial smooth muscle was alleviated,of which relieved edema of air passage、restrained inflammatory cell and so on,these would contribute to pursiness. The antiasthmatic experiments of panting guinea pigs indicated that the original prescription and Chaifang V had significance compare with control group .
Pseudoephedrine and licoflavone might play synergetic effect in antiasthmatic mechnism by the analysis of HPLC. The original prescription and Chaifang V had obvious effects of relieving cough and eliminating phlegm,but hadnot conspicuous inhibition on tumour cell.
In view of clinical medication property of Maxingshigana decoction,we developed it to dispensing granule which met“planning Treatment according to Diagnosis”needs and is easy to take and carry about.we optimized the extraction technology and establish the quality standard of dispensing granule.
Effective groups was obtained by optimizing the extraction technology, we exploited new-style product of Chinese traditional medicine,“chuankening dropping pills”.we optimized the preparation technology and set up the quality standard of dropping pills.
麻杏石甘汤四味药不同配伍后,和单煎药液相比,主要有效成分麻黄碱、苦杏仁苷和甘草酸的含量都降低,石膏的溶出量有所增加,但影响不显著。
在麻杏石甘汤共煎药液、甘草单煎药液以及有效部位组合药液中,几乎没有检测到甘草次酸的存在,这说明,甘草酸主要是经胃酸或肝中β-葡萄糖醛酸酶作用分解形成甘草次酸,从而产生了解毒,抗炎,镇咳等药理作用。
β2激动剂筛选实验表明,含有麻黄的配伍都有平喘活性,麻黄和甘草的组合活性更强。这表明,麻杏石甘汤的平喘机制应该是通过和β2受体活性部位结合,改变了受体的构象,受体被激活,使得支气管平滑肌松弛,减轻了气道水肿,抑制了炎症细胞等,有利于缓解和消除喘息。
有效部位提取物组方对致喘豚鼠的平喘实验表明,和对照组比较,原方剂和处方5平喘效果有显著性,其它处方无显著性。通过HPLC分析可知,伪麻黄碱和甘草黄酮等可能在平喘机制中起到协同作用。原方剂和处方5也有明显的镇咳和祛痰活性,但是,对肿瘤细胞没有明显的抑制作用。
根据麻杏石甘汤临床用药的特点,将其开发成为配方颗粒新型制剂,对提取工艺进行了优化,并制定了配方颗粒的质量标准。满足临床辩证论治,随症加减的需要,有利于临床医师灵活组方和患者服用。
通过工艺优化,提取得到有效部位,在药效学研究的基础上,研制开发了中药新药喘咳宁滴丸,优化了滴丸的成型工艺并制定了滴丸的质量标准。
Maxingshigan Decoction was recorded in《Treatise on Febrile Diseases》by Zhang zhong-jing in Han Dynasty, which was composed of ephedra、bitter apricot kernel、prepared licorice root and gypsum. It had the effects of clearing lung-heat and relieving cough and ashma and was often used to treat acute and chronic bronchitis、bronchial asthma and so on. In order to clarify the science and mechanism of prescription compatibility ,to give scientific evidence for exploiting new-styly product of Chinese traditional medicine,the compatible regulation and therapeutic basis were researched.
After different compatibility of four drugs,the contents of ephedrine、amygdalin and glycyrrhizinic acid were reduced,and the content of calcium sulphate was slightly increased in decoction compared with every single decoction.
Glycyrrhetic acid was not detected in the Maxingshigan Decoction、licorice root decoction and component compatibility of effective substance , this showed that glycyrrhizic acid was decomposed to generate glycyrrhetic acid by gastric acid in the stomach orβ-glucuronidase in the liver ,which contributed to detoxication、anti-inflammatory and preventing cough.
The experiment ofβ2 agonist screening showed that compatibilities with ephedra had the activity of relieving asthma. This suggested that the mechanism of alleviating asthma was that when drugs were combined with the active part ofβ2 receptor ,the conformation of receptor was changed and receptor was activated,spasm of bronchial smooth muscle was alleviated,of which relieved edema of air passage、restrained inflammatory cell and so on,these would contribute to pursiness. The antiasthmatic experiments of panting guinea pigs indicated that the original prescription and Chaifang V had significance compare with control group .
Pseudoephedrine and licoflavone might play synergetic effect in antiasthmatic mechnism by the analysis of HPLC. The original prescription and Chaifang V had obvious effects of relieving cough and eliminating phlegm,but hadnot conspicuous inhibition on tumour cell.
In view of clinical medication property of Maxingshigana decoction,we developed it to dispensing granule which met“planning Treatment according to Diagnosis”needs and is easy to take and carry about.we optimized the extraction technology and establish the quality standard of dispensing granule.
Effective groups was obtained by optimizing the extraction technology, we exploited new-style product of Chinese traditional medicine,“chuankening dropping pills”.we optimized the preparation technology and set up the quality standard of dropping pills.
引文
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