马钱子的炮制工艺及HPLC指纹图谱的研究
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摘要
马钱子具有重要的中药临床应用价值,但其毒性剧烈,中毒量与治疗量接近,若因误用,或服用过量,或炮制不得法,可引起中毒反应甚则死亡。尤其在剂量方面,许多有关马钱子毒性反应的报道均由于服用马钱子剂量过大引起。但临床应用时若剂量太小又达不到较好的疗效。现代医药学者对马钱子的化学成分,药理作用方面的研究已达到很高水准,但对其量效关系的研究目前仍很少,毒理学方面的研究也不够深入。因此,以中医药理论为基础,结合现代实验研究手段,系统探讨马钱子用药剂量的差异与临床效用的关系及马钱子毒性方面的问题有着较为广阔的前景。
祖国医药学研究表明,马钱子味苦,性温,有大毒,归肝,脾经。主要功能为通络止痛,散结消肿。用于治疗风湿顽痹,麻木瘫痪,跌扑损伤,痈疽肿痛等。现代医药学文献研究表明,马钱子含多种生物碱,药理作用广泛,可用于治疗内科、外科、五官科等疾病。马钱子的主要有毒成分为番木鳖碱和马钱子碱。若服用过量,可引起肢体颤动、惊厥、呼吸困难、昏迷。影响马钱子毒性的因素很多,主要有剂量、炮制、配伍、剂型等方面。
本论文用HPLC法对马钱子的江西炮制方法及其改良法炮制品中士的宁和马钱子碱含量进行测定。色谱柱填料为硅胶,流动相为正己烷一二氯甲烷一甲醇一浓氨溶液(47.5∶47.5∶5∶0.35),检测波长为254nm。江西法炮制品中士的宁和马钱子碱的含量较低。该法精确、简便、重现性好。
以马钱子为研究对象,采用HPLC法进行色谱指纹图谱研究。建立了马钱子药材HPLC指纹图谱。以甲醇-水-浓盐酸(50∶50∶1)为提取溶剂,超声波震荡30min,制备马钱子药材样品溶液;采用RP-HPLC(DAD)法,选用Kromasil KR100-5C18色谱柱,流速1ml/min,检测波长254nm,流动相为乙腈(B)-0.2%三乙胺-0.2%乙酸溶液(A),梯度洗脱(v/v):0min时8%∶92%,30min时17%∶83%,60min时60%∶40%,对10批马钱子药材进行测定,以士的宁为参照物,标定了具有代表性的12个峰作为共有峰;通过方法学验证,精密度、稳定性、重现性试验RSD均小于3%;采用相似度作为指纹图谱的评判参数,计算了不同批次与对照指纹图谱之间的相似度均大于0.9,表明10批药材质量均一、稳定。该研究方法为马钱子药材的质量控制提供了参考。
Nux vomica has important value in the clinical application of Traditional Chinese Medicine. But its toxicity is evident, toxic dose is about in accordance with therapeutic dose. The high-dosage induces easily toxication and death, but the low-dosage can't show obvious effect in clinic use. Research development on chemical constituents and pharmacological action is obvious, but study on the dose-effect relationship and toxicology is not sufficient at present. Therefore, based on diagnosis and treatment of fundamental knowledge of TCM and modern experiment, there exists broad prospect by systemly studying dose-effect relationship and toxicity of Nux vomica.
The research of TCM documents shows that Nux vomica is bitter, warm and poisonous. Its meridian orientation is liver and spleen. It can't only unblock collaterals and disperse lumps, but also relieve swelling and stop pain. To be used in swelling and pain from carbuncles, falls, contusion and pain in Bi syndromes due to wind-damp. The research of west medicine documents shows that Nux vomica has more alkaloids and pharmacological action is evident. It has higher use value in clinic about internal, surgical diseases and disease sofe eye, ear, nose and throat. The chief toxic ingredients of Nux vomica are stryehnine and brucine. Syndromes of vibration in the extremity, faint due to emotional upset, dyspnoea respiration and coma would be occurred if used in large dosages. The affection factors to toxicity of Nux vomica are dosage, processing, compatibility, forms of prepared herbs and so on.
Studying on HPLC fingerprints of Semen Strychni has been described in this thesis. The HPLC fingerprint of Semen Strychni was established. The extraction methods was ultrasonic for 30 min by methanol-H_2O-HCl (50:50:1) .Then determined by RP-HPLC(DAD), the chromatographic column was Kromasil KR100-5 C18, flow rate at 1.0ml/min and the detection wavelength was 254nm. The gradient elution mode was applied in chromatographic separation,the mobile phase was acetonitrile (B)-0.2% triethylamine -0.2% glacial acetic acid water (A) (v/v): 0min, 8%:92%;30min,17%:83%;60min,60%:40%.12 common peaks were found in the fingerprints of 10 batches of Semen Strychni,and good similarities with correlation coefficients higher than 0.99 were found in fingerprints between the herbs from different batches and the standard chromatographic fingerprint. The method is accurate and reproducible,providing a new reference for quality control of Semen Strychni.
祖国医药学研究表明,马钱子味苦,性温,有大毒,归肝,脾经。主要功能为通络止痛,散结消肿。用于治疗风湿顽痹,麻木瘫痪,跌扑损伤,痈疽肿痛等。现代医药学文献研究表明,马钱子含多种生物碱,药理作用广泛,可用于治疗内科、外科、五官科等疾病。马钱子的主要有毒成分为番木鳖碱和马钱子碱。若服用过量,可引起肢体颤动、惊厥、呼吸困难、昏迷。影响马钱子毒性的因素很多,主要有剂量、炮制、配伍、剂型等方面。
本论文用HPLC法对马钱子的江西炮制方法及其改良法炮制品中士的宁和马钱子碱含量进行测定。色谱柱填料为硅胶,流动相为正己烷一二氯甲烷一甲醇一浓氨溶液(47.5∶47.5∶5∶0.35),检测波长为254nm。江西法炮制品中士的宁和马钱子碱的含量较低。该法精确、简便、重现性好。
以马钱子为研究对象,采用HPLC法进行色谱指纹图谱研究。建立了马钱子药材HPLC指纹图谱。以甲醇-水-浓盐酸(50∶50∶1)为提取溶剂,超声波震荡30min,制备马钱子药材样品溶液;采用RP-HPLC(DAD)法,选用Kromasil KR100-5C18色谱柱,流速1ml/min,检测波长254nm,流动相为乙腈(B)-0.2%三乙胺-0.2%乙酸溶液(A),梯度洗脱(v/v):0min时8%∶92%,30min时17%∶83%,60min时60%∶40%,对10批马钱子药材进行测定,以士的宁为参照物,标定了具有代表性的12个峰作为共有峰;通过方法学验证,精密度、稳定性、重现性试验RSD均小于3%;采用相似度作为指纹图谱的评判参数,计算了不同批次与对照指纹图谱之间的相似度均大于0.9,表明10批药材质量均一、稳定。该研究方法为马钱子药材的质量控制提供了参考。
Nux vomica has important value in the clinical application of Traditional Chinese Medicine. But its toxicity is evident, toxic dose is about in accordance with therapeutic dose. The high-dosage induces easily toxication and death, but the low-dosage can't show obvious effect in clinic use. Research development on chemical constituents and pharmacological action is obvious, but study on the dose-effect relationship and toxicology is not sufficient at present. Therefore, based on diagnosis and treatment of fundamental knowledge of TCM and modern experiment, there exists broad prospect by systemly studying dose-effect relationship and toxicity of Nux vomica.
The research of TCM documents shows that Nux vomica is bitter, warm and poisonous. Its meridian orientation is liver and spleen. It can't only unblock collaterals and disperse lumps, but also relieve swelling and stop pain. To be used in swelling and pain from carbuncles, falls, contusion and pain in Bi syndromes due to wind-damp. The research of west medicine documents shows that Nux vomica has more alkaloids and pharmacological action is evident. It has higher use value in clinic about internal, surgical diseases and disease sofe eye, ear, nose and throat. The chief toxic ingredients of Nux vomica are stryehnine and brucine. Syndromes of vibration in the extremity, faint due to emotional upset, dyspnoea respiration and coma would be occurred if used in large dosages. The affection factors to toxicity of Nux vomica are dosage, processing, compatibility, forms of prepared herbs and so on.
Studying on HPLC fingerprints of Semen Strychni has been described in this thesis. The HPLC fingerprint of Semen Strychni was established. The extraction methods was ultrasonic for 30 min by methanol-H_2O-HCl (50:50:1) .Then determined by RP-HPLC(DAD), the chromatographic column was Kromasil KR100-5 C18, flow rate at 1.0ml/min and the detection wavelength was 254nm. The gradient elution mode was applied in chromatographic separation,the mobile phase was acetonitrile (B)-0.2% triethylamine -0.2% glacial acetic acid water (A) (v/v): 0min, 8%:92%;30min,17%:83%;60min,60%:40%.12 common peaks were found in the fingerprints of 10 batches of Semen Strychni,and good similarities with correlation coefficients higher than 0.99 were found in fingerprints between the herbs from different batches and the standard chromatographic fingerprint. The method is accurate and reproducible,providing a new reference for quality control of Semen Strychni.
引文
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