地耳草的品质评价研究
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摘要
本文以地耳草为研究对象,对地耳草的有效成分及有害物质进行了含量分析,对地耳草的指纹图谱进行了研究,并对不同生长期地耳草有效物质的动态积累和变化规律进行了研究,为地耳草药材的质量评价及其质量标准制订提供了可靠依据。主要研究内容与结果如下：
1.地耳草商品药材的鉴定研究。用传统鉴定方法及现代鉴定技术,从药材性状、显微特征、薄层色谱及HPLC指纹图谱等方面,建立地耳草及其易混品细叶金丝桃的鉴定方法；以有效成分定量分析结合指纹图谱整体分析的模式,评价商品地耳草的品质。
2.UV-VIS法测定地耳草总黄酮的含量。选取槲皮素作对照品,以测定的槲皮素含量来作为地耳草中总黄酮含量的计算指标,测定值与真实值有一定差异,本实验旨在对不同产地地耳草中总黄酮的含量作量化比较,评价药材质量。
3.HPLC法测定六种黄酮类单体的含量。供试品制备用80%甲醇50mL,根据本实验供试品制备的优化结果,认为回流提取90min×3所得6种黄酮的总量最高。选取地耳草已知明确的六种黄酮类单体(芦丁、金丝桃苷、异槲皮苷、槲皮苷、槲皮素、山柰酚)作对照品,采用HPLC法同时测定六种黄酮类单体的含量。此测定方法,准确可靠,灵敏度高,重现性良好,为地耳草质量标准评价研究提供了科学依据。
4.建立高效毛细管电泳二极管阵列检测法(HPCE-DAD)同时测定地耳草中芦丁、异槲皮苷、金丝桃苷、金丝桃苷、槲皮苷、山奈酚及槲皮素含量的方法。选择毛细管区带电泳分离模式,以40 mmol·L-1硼砂缓冲液(pH8.62)为电泳介质,未涂渍标准熔融石英毛细管(75μmi.d.×64.5 cm,有效长度56 cm)为分离通道,,分离电压为25 kV,检测波长为206nm,毛细管温度为25℃,压力进样为50 mbar,8 s。6种黄酮的峰面积与浓度的线性关系良好(r>0.9953)；加样回收率为98.8～102.9%。该方法简单、准确,重现性较好,可用于地耳草药材质量的评价和控制。
5.电感耦合等离子发射光谱法(ICP)和微波消解—原子荧光光谱法测定21种无机元素的含量(16种微量元素和5种重金属元素)。并用SPSS16.0对数据进行分析处理,获得了地耳草无机元素含量的准确信息,可为地耳草微量元素的药效药理研究提供科学依据,同时还将不同产地的微量元素制成元素分布图谱,可以进行地耳草的真伪鉴别。
6.建立了地耳草高效液相色谱指纹图谱质控方法,可为地耳草样品的质量和品种鉴定提供全面的信息和检测标准。不同产地及不同采收期地耳草样品的HPLC指纹图谱结果表明,产地不同,地耳草样品之间的相似度有一定的差异,这可能与地耳草生长的不同地理条件,不同气候以及不同的品种有关,同一产地的地耳草样品的高效液相指纹图谱有较好的相似度,实现对地耳草药材质量的整体评价。
7.建立了地耳草毛细管电泳指纹图谱质控方法,可为地耳草样品的质量和品种鉴定提供全面的信息和检测标准,实现对地耳草药材质量的整体评价。
8. HSGC-MS联用技术对不同产地地耳草进行分析,测定其总离子流指纹图谱,确定共有峰,并对部分色谱峰进行了初步归属,初步建立了以12个共有峰为特征指纹信息的HSGC-MS (?)旨纹图谱,发现地耳草样品之间的相似度有一定的差异。该方法准确可靠,重现性好,可作为地耳草内在质量评价的依据。
9. UPLC-MS联用技术对不同产地地耳草进行分析,测定其总离子流图谱,并对部分色谱峰进行了初步归属,通过与对照品及相关质谱数据比较分析,初步鉴定其中8种黄酮类化合物,并用UPLC-DAD法对6种黄酮类化合物的含量同时测定。该方法准确可靠,重现性好,可作为地耳草内在质量评价的依据。
10.不同采收期地耳草有效物质的动态积累及变化规律研究。用现代分析技术,以有效成分定量分析结合指纹图谱整体评价的模式,对不同生长时间地耳草中黄酮类成分、挥发性成分、无机元素等有效物质的动态积累及变化规律进行分析研究,为确定药材的适宜采收期提供科学依据。
11.气候因子对药材有效物质合成和积累的影响研究。考察气候因子(气温、光照时数、降水量、相对湿度等),以药材中有效物质黄酮类成分(总黄酮和芦丁、异槲皮苷、槲皮苷、槲皮素及山柰酚等)、挥发性成分、无机元素的累积量为考核指标,采用UV和HPLC、HPCE等对不同气候因子作用下药材有效物质的变化及其规律进行研究,用逐步回归法分析了气候因子对有效物质积累的影响,探讨气候因子与有效物质积累的相关性。
论文主要创新点：
1、探究不同物候期地耳草有效物质的动态积累及变化规律,为确定地耳草的最佳采收期提供依据；分析气候因子与有效物质积累的相关性,揭示影响有效物质含量主导因子,为优质药材的生产提供理论指导。
2、以多种有效成分同时定量分析结合指纹图谱整体评价的模式,建立地耳草品质和安全性的科学评价体系。
3、首次建立地耳草中芦丁、金丝桃苷、异槲皮苷、槲皮苷、槲皮素及山柰酚6种活性成分同时测定的HPLC-DAD、HPCE-DAD分析方法。
4、首次建立不同产地、不同采收期和不同种属地耳草的HPCE-DAD、HSGC-MS指纹图谱分析方法。
In this dissertation, isolation of the effective component and harmful substances in Herba Hyperici Japonici, the fingerprinting of Herba Hyperici Japonici based on activity constituent are studied and growth of different effective material accumulation and the dynamic changes were studied.Towards these objectives,the following discussed in the thesis.
1.The identification of medicinal products. Identified using traditional methods and modern identification techniques, from the medicinal properties, microscopic characteristics, thin-layer chromatography and HPLC fingerprint, etc., set up Herba Hyperici Japonici and Its Adulterant identification methods; to the active ingredients of quantitative analysis combined with the overall analysis of fingerprint patterns, evaluation of the quality of merchandise Herba Hyperici Japonici.
2.Using UV-VIS Determination of total flavonoids content, quercetin select for reference substance to determine the content of quercetin Herba Hyperici Japonici as flavonoid content in the calculation of the total target, determination of value and there is a certain difference between the true value, the experiment aimed at different places on Herba Hyperici Japonici. The content of total flavonoids quantified for comparison, the evaluation of the quality of medicines.
3.Determination by HPLC of six monomer flavonoids. under samples prepared with 80% methanol 50mL, According to this study prepared for the trial to optimize the results of goods that reflux extraction 90min×3 to determine. The total content of the amendment to provide a scientific basis. It select six known flavonoid monomers (rutin, hyperoside, isoquercitrin, quercitrin, quercetin and kaempferol) as reference substance, the use of HPLC method for simultaneous determination of six flavonoids monomer content. This method, accurate and reliable, high sensitivity, good reproducibility, quality standards for the evaluation of Herba Hyperici Japonici study provides a scientific basis.
4.To establish a high performance capillary electrophoresis method with diode array detection (HPCE-DAD) for simultaneous determination of rutin, isoquercitrin, hyperoside, quercitrin, kaempferol and quercetin in Herba Hyperici Japonici. Based on the mode of capillary zone electrophoresis,40 mmol·L-1 borax was used as buffer solution (pH8.62), uncoated fused silica capillary (56 cm/64.5 cm×75μm id) was used, separation voltage was 25 kV, detection wavelength was at 206nm, column temperature was maintained at 25℃, and sample was injected at 50 mbar,8 s. Six Flavonoids showed good linearity (r >0.9953) in the range of the tested concentration, the average recoveries of the method were between 98.8-102.9%. The method is simple, accurate and reproducible, and can be used for quality control of Herba Hyperici Japonici.
5.The content of 21 inorganic elements (11kinds of trace elements and heavy metals five 5) are analyzed with advanced means of ICP and microwave digestion-AFS, use the SPSS 16.0 to accurate information the accurate information of inorganic elements of Herba Hyperici Japonici is obtained.The results provide a scientific basis for the quality evaluating of Herba Hyperici Japonici, but also inorganic elements distribution map is developed, it can identify the authenticity of Herba Hyperici Japonici.
6.A simple and reliable high performance liquid chromatographic(HPLC)method has been developed and validated for the fingerprinting of extracts from the Herba Hyperici Japonici. The fingerpints of different samples are different, because of differences in plant species or variations in environmental conditions of the growth locations of the plant.For the Herba Hyperici Japonici from same location, the fingerprints of the samples shoe closely similar fingerprints. So the HPLC fingerprinting technique has high potential in herb autheticaton application.
7.A simple and reliable high performance Capillary Electrophoresis method has been developed and validated for the fingerprinting of extracts from the Herba Hyperici Japonici. Herba Hyperici Japonici on the implementation of the overall evaluation of the quality of medicin.
8.HSGC-MS in conjunction with technology from different areas of Herba Hyperici Japonici analysis, determination of the total ion current fingerprint to determine the total peak, and part of chromatographic peaks for the initial vesting, the initial set up a peak for a total of 12 fingerprint HSGC-MS information of the fingerprint, found a small number of samples HSGC-MS fingerprint of a significant difference. This method is accurate and reliable, reproducible and can be used as the internal quality evaluation of leaf venetum basis.
9.UPLC-MS in conjunction with technology from different areas of Herba Hyperici Japonici analysis, determination of the total ion-current figure to determine the total peak, and 8 chromatographic peaks for the initial vesting, at the same time, determination by UPLC-DAD of six monomer flavonoid. This method is accurate and reliable, reproducible and can be used as the internal quality evaluation of leaf venetum basis.
10O.Harvesting period of different dynamic analysis of changes in modern technology, combined with quantitative analysis of active ingredient overall evaluation of fingerprint pattern of growth for different time Herba Hyperici Japonici, volatile components, and other inorganic elements in the dynamic accumulation of effective substances and Analysis of changes in laws, in order to determine the best ingredients to provide a scientific basis for harvest time.
11.Climatic factors on the synthesis of medicinal substances and the accumulation of the effective impact of research. Study climatic factors (temperature, light hours, precipitation, relative humidity, etc.) to medicinal substances in the effective flavonoids (total flavonoids and rutin, isoquercitrin, quercitrin, quercetin and kaempferol, etc.), volatile component of the cumulative target of evaluation, using UV and HPLC, HPCE, such as the role of climatic factors on the different ingredients of change and its effective material to study the law, using stepwise regression analysis of climatic factors on the effective impact of the accumulation of material to explore the climate factor and effective accumulation of the relevance of the material.
The main feature and innovation in this thesis are presented:
1 To explore the different phenology of Herba Hyperici Japonici effective substances and changes in the dynamic accumulation, Climatic factors and the effective accumulation of the relevance of the material, for the production of high-quality ingredients to provide theoretical guidance.
2 To establish the quality and safety of Herba Hyperici Japonici scientific evaluation system by Quantitative analysis of the active ingredient in combination fingerprint pattern of the overall evaluation.
3 To establish the method of rutin, hyperoside, isoquercitrin, quercitrin, quercetin and kaempferol 6 Determination of the active ingredient at the same time by the HPLC-DAD, HPCE-DAD analysis first time.
4 To esstablish the HPCE-DAD、HSGC-MS finger print analytical method of Herba Hyperici Japonici in differet habit, collection period and kind.
1.地耳草商品药材的鉴定研究。用传统鉴定方法及现代鉴定技术,从药材性状、显微特征、薄层色谱及HPLC指纹图谱等方面,建立地耳草及其易混品细叶金丝桃的鉴定方法；以有效成分定量分析结合指纹图谱整体分析的模式,评价商品地耳草的品质。
2.UV-VIS法测定地耳草总黄酮的含量。选取槲皮素作对照品,以测定的槲皮素含量来作为地耳草中总黄酮含量的计算指标,测定值与真实值有一定差异,本实验旨在对不同产地地耳草中总黄酮的含量作量化比较,评价药材质量。
3.HPLC法测定六种黄酮类单体的含量。供试品制备用80%甲醇50mL,根据本实验供试品制备的优化结果,认为回流提取90min×3所得6种黄酮的总量最高。选取地耳草已知明确的六种黄酮类单体(芦丁、金丝桃苷、异槲皮苷、槲皮苷、槲皮素、山柰酚)作对照品,采用HPLC法同时测定六种黄酮类单体的含量。此测定方法,准确可靠,灵敏度高,重现性良好,为地耳草质量标准评价研究提供了科学依据。
4.建立高效毛细管电泳二极管阵列检测法(HPCE-DAD)同时测定地耳草中芦丁、异槲皮苷、金丝桃苷、金丝桃苷、槲皮苷、山奈酚及槲皮素含量的方法。选择毛细管区带电泳分离模式,以40 mmol·L-1硼砂缓冲液(pH8.62)为电泳介质,未涂渍标准熔融石英毛细管(75μmi.d.×64.5 cm,有效长度56 cm)为分离通道,,分离电压为25 kV,检测波长为206nm,毛细管温度为25℃,压力进样为50 mbar,8 s。6种黄酮的峰面积与浓度的线性关系良好(r>0.9953)；加样回收率为98.8～102.9%。该方法简单、准确,重现性较好,可用于地耳草药材质量的评价和控制。
5.电感耦合等离子发射光谱法(ICP)和微波消解—原子荧光光谱法测定21种无机元素的含量(16种微量元素和5种重金属元素)。并用SPSS16.0对数据进行分析处理,获得了地耳草无机元素含量的准确信息,可为地耳草微量元素的药效药理研究提供科学依据,同时还将不同产地的微量元素制成元素分布图谱,可以进行地耳草的真伪鉴别。
6.建立了地耳草高效液相色谱指纹图谱质控方法,可为地耳草样品的质量和品种鉴定提供全面的信息和检测标准。不同产地及不同采收期地耳草样品的HPLC指纹图谱结果表明,产地不同,地耳草样品之间的相似度有一定的差异,这可能与地耳草生长的不同地理条件,不同气候以及不同的品种有关,同一产地的地耳草样品的高效液相指纹图谱有较好的相似度,实现对地耳草药材质量的整体评价。
7.建立了地耳草毛细管电泳指纹图谱质控方法,可为地耳草样品的质量和品种鉴定提供全面的信息和检测标准,实现对地耳草药材质量的整体评价。
8. HSGC-MS联用技术对不同产地地耳草进行分析,测定其总离子流指纹图谱,确定共有峰,并对部分色谱峰进行了初步归属,初步建立了以12个共有峰为特征指纹信息的HSGC-MS (?)旨纹图谱,发现地耳草样品之间的相似度有一定的差异。该方法准确可靠,重现性好,可作为地耳草内在质量评价的依据。
9. UPLC-MS联用技术对不同产地地耳草进行分析,测定其总离子流图谱,并对部分色谱峰进行了初步归属,通过与对照品及相关质谱数据比较分析,初步鉴定其中8种黄酮类化合物,并用UPLC-DAD法对6种黄酮类化合物的含量同时测定。该方法准确可靠,重现性好,可作为地耳草内在质量评价的依据。
10.不同采收期地耳草有效物质的动态积累及变化规律研究。用现代分析技术,以有效成分定量分析结合指纹图谱整体评价的模式,对不同生长时间地耳草中黄酮类成分、挥发性成分、无机元素等有效物质的动态积累及变化规律进行分析研究,为确定药材的适宜采收期提供科学依据。
11.气候因子对药材有效物质合成和积累的影响研究。考察气候因子(气温、光照时数、降水量、相对湿度等),以药材中有效物质黄酮类成分(总黄酮和芦丁、异槲皮苷、槲皮苷、槲皮素及山柰酚等)、挥发性成分、无机元素的累积量为考核指标,采用UV和HPLC、HPCE等对不同气候因子作用下药材有效物质的变化及其规律进行研究,用逐步回归法分析了气候因子对有效物质积累的影响,探讨气候因子与有效物质积累的相关性。
论文主要创新点：
1、探究不同物候期地耳草有效物质的动态积累及变化规律,为确定地耳草的最佳采收期提供依据；分析气候因子与有效物质积累的相关性,揭示影响有效物质含量主导因子,为优质药材的生产提供理论指导。
2、以多种有效成分同时定量分析结合指纹图谱整体评价的模式,建立地耳草品质和安全性的科学评价体系。
3、首次建立地耳草中芦丁、金丝桃苷、异槲皮苷、槲皮苷、槲皮素及山柰酚6种活性成分同时测定的HPLC-DAD、HPCE-DAD分析方法。
4、首次建立不同产地、不同采收期和不同种属地耳草的HPCE-DAD、HSGC-MS指纹图谱分析方法。
In this dissertation, isolation of the effective component and harmful substances in Herba Hyperici Japonici, the fingerprinting of Herba Hyperici Japonici based on activity constituent are studied and growth of different effective material accumulation and the dynamic changes were studied.Towards these objectives,the following discussed in the thesis.
1.The identification of medicinal products. Identified using traditional methods and modern identification techniques, from the medicinal properties, microscopic characteristics, thin-layer chromatography and HPLC fingerprint, etc., set up Herba Hyperici Japonici and Its Adulterant identification methods; to the active ingredients of quantitative analysis combined with the overall analysis of fingerprint patterns, evaluation of the quality of merchandise Herba Hyperici Japonici.
2.Using UV-VIS Determination of total flavonoids content, quercetin select for reference substance to determine the content of quercetin Herba Hyperici Japonici as flavonoid content in the calculation of the total target, determination of value and there is a certain difference between the true value, the experiment aimed at different places on Herba Hyperici Japonici. The content of total flavonoids quantified for comparison, the evaluation of the quality of medicines.
3.Determination by HPLC of six monomer flavonoids. under samples prepared with 80% methanol 50mL, According to this study prepared for the trial to optimize the results of goods that reflux extraction 90min×3 to determine. The total content of the amendment to provide a scientific basis. It select six known flavonoid monomers (rutin, hyperoside, isoquercitrin, quercitrin, quercetin and kaempferol) as reference substance, the use of HPLC method for simultaneous determination of six flavonoids monomer content. This method, accurate and reliable, high sensitivity, good reproducibility, quality standards for the evaluation of Herba Hyperici Japonici study provides a scientific basis.
4.To establish a high performance capillary electrophoresis method with diode array detection (HPCE-DAD) for simultaneous determination of rutin, isoquercitrin, hyperoside, quercitrin, kaempferol and quercetin in Herba Hyperici Japonici. Based on the mode of capillary zone electrophoresis,40 mmol·L-1 borax was used as buffer solution (pH8.62), uncoated fused silica capillary (56 cm/64.5 cm×75μm id) was used, separation voltage was 25 kV, detection wavelength was at 206nm, column temperature was maintained at 25℃, and sample was injected at 50 mbar,8 s. Six Flavonoids showed good linearity (r >0.9953) in the range of the tested concentration, the average recoveries of the method were between 98.8-102.9%. The method is simple, accurate and reproducible, and can be used for quality control of Herba Hyperici Japonici.
5.The content of 21 inorganic elements (11kinds of trace elements and heavy metals five 5) are analyzed with advanced means of ICP and microwave digestion-AFS, use the SPSS 16.0 to accurate information the accurate information of inorganic elements of Herba Hyperici Japonici is obtained.The results provide a scientific basis for the quality evaluating of Herba Hyperici Japonici, but also inorganic elements distribution map is developed, it can identify the authenticity of Herba Hyperici Japonici.
6.A simple and reliable high performance liquid chromatographic(HPLC)method has been developed and validated for the fingerprinting of extracts from the Herba Hyperici Japonici. The fingerpints of different samples are different, because of differences in plant species or variations in environmental conditions of the growth locations of the plant.For the Herba Hyperici Japonici from same location, the fingerprints of the samples shoe closely similar fingerprints. So the HPLC fingerprinting technique has high potential in herb autheticaton application.
7.A simple and reliable high performance Capillary Electrophoresis method has been developed and validated for the fingerprinting of extracts from the Herba Hyperici Japonici. Herba Hyperici Japonici on the implementation of the overall evaluation of the quality of medicin.
8.HSGC-MS in conjunction with technology from different areas of Herba Hyperici Japonici analysis, determination of the total ion current fingerprint to determine the total peak, and part of chromatographic peaks for the initial vesting, the initial set up a peak for a total of 12 fingerprint HSGC-MS information of the fingerprint, found a small number of samples HSGC-MS fingerprint of a significant difference. This method is accurate and reliable, reproducible and can be used as the internal quality evaluation of leaf venetum basis.
9.UPLC-MS in conjunction with technology from different areas of Herba Hyperici Japonici analysis, determination of the total ion-current figure to determine the total peak, and 8 chromatographic peaks for the initial vesting, at the same time, determination by UPLC-DAD of six monomer flavonoid. This method is accurate and reliable, reproducible and can be used as the internal quality evaluation of leaf venetum basis.
10O.Harvesting period of different dynamic analysis of changes in modern technology, combined with quantitative analysis of active ingredient overall evaluation of fingerprint pattern of growth for different time Herba Hyperici Japonici, volatile components, and other inorganic elements in the dynamic accumulation of effective substances and Analysis of changes in laws, in order to determine the best ingredients to provide a scientific basis for harvest time.
11.Climatic factors on the synthesis of medicinal substances and the accumulation of the effective impact of research. Study climatic factors (temperature, light hours, precipitation, relative humidity, etc.) to medicinal substances in the effective flavonoids (total flavonoids and rutin, isoquercitrin, quercitrin, quercetin and kaempferol, etc.), volatile component of the cumulative target of evaluation, using UV and HPLC, HPCE, such as the role of climatic factors on the different ingredients of change and its effective material to study the law, using stepwise regression analysis of climatic factors on the effective impact of the accumulation of material to explore the climate factor and effective accumulation of the relevance of the material.
The main feature and innovation in this thesis are presented:
1 To explore the different phenology of Herba Hyperici Japonici effective substances and changes in the dynamic accumulation, Climatic factors and the effective accumulation of the relevance of the material, for the production of high-quality ingredients to provide theoretical guidance.
2 To establish the quality and safety of Herba Hyperici Japonici scientific evaluation system by Quantitative analysis of the active ingredient in combination fingerprint pattern of the overall evaluation.
3 To establish the method of rutin, hyperoside, isoquercitrin, quercitrin, quercetin and kaempferol 6 Determination of the active ingredient at the same time by the HPLC-DAD, HPCE-DAD analysis first time.
4 To esstablish the HPCE-DAD、HSGC-MS finger print analytical method of Herba Hyperici Japonici in differet habit, collection period and kind.
引文
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[6]傅凡.田基黄活性成分的研究[D].第二军医大学学位论文.2005
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[17]苏娟,等.田基黄提取物保肝作用的实验研究[J].药学实践杂志,2005,23(6)342-344
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[21]王桂英.抗癌中药的研究[J].国外医学肿瘤学分册,1980,7
[22]周小玲,柯美珍,宋志军.田基黄对大鼠呼吸道及全身免疫功能的影响[J].广西医科大学学报,2001,18(2)：211-212
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[24]张素芹,邱海霞.田基黄的研究概况[J].中国中医药科技,1999,6(5)：351-352
[25]吴移谋,占利生.田基黄水煎剂对Ⅱ型单纯疱疹病毒复制的抑制作用[J].湖南微生物学通讯,1990(2)：7-10
[26]李建良,朱照娟.田基黄治疗内脏出血[J].时珍国药研究,1994,5(1)：4748
[27]Jain-S,蔡幼清(译).田基黄中一种黄酮混合物对小鼠雌激素和妊娠的阻断效果[J].国外医学·中医中药分册,1994,16(4)：42
[28]许乾丽,熊慧林,茅向军.黔产3种金丝桃属植物药中金丝桃苷的含量测定[J].药物分析杂志,2003,23(6)：414416
[29]田刚,彭国平.高效液相色谱法测定地耳草中槲皮素的含量[J].中国中药杂志,2004,29(5)：476-478
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[31]彭维,吴钉红,杨立伟,等.田基黄药材的质量研究[J].中南药学,2006,4(5)：340-342
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[35]秦盛莹,陈晓辉,米丹,等RP-HPLC法测定田基黄中异巴西红厚壳素的含量[J].药物分析杂志,2007,27(5)：718-720
[36]韩乐,刘训红,王丽娟,等.地耳草挥发性成分的HSGC-MS分析[J].中国药师,2010,13(6)：770-773
[37]韩乐,刘训红,王丽娟,等.地耳草挥发性成分HSGC/MS分析及其动态研究[J].质 谱学报,2010,31(4)：142-146
[38]祝兴勇,杨群,陶静.HPLC测定田基黄胶囊中槲皮素含量探讨[J].九江学院学报(自然科学版),2005,4,60-61
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[40]王永刚,杨立伟,苏薇薇.田基黄药材指纹图谱研究[J].南方医科大学学报,2006,26(7)：1001-1002.
[41]吴忠,杨立伟,王永刚,等.田基黄注射液HPLC指纹图谱研究[J].中药材,2004,27(6)：441-442.
[42]苏薇薇,杨立伟,王永刚.利用指纹图谱技术监控田基黄注射液的生产过程[J].中药材,2004,27(9)：672-673
[43]韩乐,刘训红,王丽娟,等.地耳草HSGC-MS(?)旨纹图谱的研究[J].现代中药研究与实践,2011,25(1)：22-24
[44]陈丽云,杨立伟,苏薇薇,等.田基黄及其注射液的研究进展[J].中药材,2002,25(7)：525-528
[45]孙忠义,黎七雄.田基黄治疗原发性肝癌30例[J].中西医结合肝炎病杂志,1995,5(4)：29-30
[46]Leuscher J.2nd International Congress on Phytomedicine and 7th Congress of the German Society of Phytotherapy, September 11-14 1996, Munich, Germany, SL-80
[47]Wheatly D.2nd International Congress on Phytomedicine and 7th Congress of the German Society of Phytotherapy, September 11-14 1996, Munich, Germany, SL-86
[48]陈厚平,肖新成.田基黄茶治疗高脂血症的疗效观察[J].中国医药导报,2006,3(30)：92
[2]钱崇澍,陈焕镛.中国植物志[M].科学出版社,1959：47-58
[3]高玉红；杨艳红.地耳草的化学成分与药理活性[J].国外医药·植物药分册,2005(3)：1406
[4]王永刚,吴钉红,杨立伟,等.田基黄中一种不稳定黄酮的研究.中药材,2005,28(6)：468-469
[5]Ishiguro K, et al. Bisxanthones fom Hypericum japonicum. Inhibitors of PAF-Induced HyPotension*[J]. Planta Med,2002,68:258-261
[6]傅凡.田基黄活性成分的研究[D].第二军医大学学位论文.2005
[7]辛义周,张希成,唐文照.地耳草的化学成分及药理作用研究进展.山东医药工业,2003,22(2)：28-29
[8]李沛波,王永刚,吴钉红,等.田基黄中三个黄酮类化合物保肝退黄作用的实验研究.中山大学学报(医学科学版),2007,28(1)：40-43
[9]顾明国,冯淑珍,王小燕.地耳草抗疟有效成分的研究—地耳草素A、B、C、D的分离和结构[J].化学学报,1988,46(3)：246-257
[10]Ishiguro K, Yamaki M, Kashihara M, et al. Saorthralin A and B, New Antibiotic Compound from Hypericum japonicum[J]. planta Med,1986, (4):288-290
[11]Ishiguro K, Yamaki M,Kashihara M,et al. Saorthralin G, A Antimicrobial Compound from Hypericum japonicum[J]. planta Med,1990,56(3):274-276
[12]Ishiguro K, Yamaki M, Kashihara M, et al. Saorthralin A, B and C:Additional Antibiotic Compound from Hypericum japonicum[J]. planta Med,1987,53:415-417
[13]吕杰,孔令义.田基黄的化学成分研究[J].中国现代中药,2007,9(11)：12-14
[14]郁建平,占练权,周欣.田基黄茎、花叶挥发油化学成分的研究[J].中国药学杂志2001,36(3)：199-200
[15]彭仁绣,等.地耳草(田基黄)注射液对四氯化碳引起小鼠肝损伤的保护作用[J].中草药,1992,23(6)：311
[16]犁七雄,彭仁绣,高平.田基黄注射液对小鼠醋氨酚肝脏毒性的保护作用[J].中国药学杂志,1992,27(8)：472475
[17]苏娟,等.田基黄提取物保肝作用的实验研究[J].药学实践杂志,2005,23(6)342-344
[18]王云庭.复方田基黄胶囊治疗慢性乙型肝炎69例的临床观察[J].中国医疗前沿,2008,3(14)：64-65
[19]金辉喜,李金荣.田基黄对人舌癌细胞株TSCCa细胞毒作用的研究.临床口腔医学杂志.1997,13(1)：19-20
[20]黎七雄,孙忠义,陈金和.田基黄对人喉癌Hep-2和人宫颈癌Hela细胞株生长的抑制作用[J].华西药学杂志,1993,8(2)：93-94
[21]王桂英.抗癌中药的研究[J].国外医学肿瘤学分册,1980,7
[22]周小玲,柯美珍,宋志军.田基黄对大鼠呼吸道及全身免疫功能的影响[J].广西医科大学学报,2001,18(2)：211-212
[23]宋志军,干潮临,程建样,等.鱼腥草、田基黄和丁公藤注射液对大鼠免疫功能的影响[J].中草药,1993,24(12)：643-644
[24]张素芹,邱海霞.田基黄的研究概况[J].中国中医药科技,1999,6(5)：351-352
[25]吴移谋,占利生.田基黄水煎剂对Ⅱ型单纯疱疹病毒复制的抑制作用[J].湖南微生物学通讯,1990(2)：7-10
[26]李建良,朱照娟.田基黄治疗内脏出血[J].时珍国药研究,1994,5(1)：4748
[27]Jain-S,蔡幼清(译).田基黄中一种黄酮混合物对小鼠雌激素和妊娠的阻断效果[J].国外医学·中医中药分册,1994,16(4)：42
[28]许乾丽,熊慧林,茅向军.黔产3种金丝桃属植物药中金丝桃苷的含量测定[J].药物分析杂志,2003,23(6)：414416
[29]田刚,彭国平.高效液相色谱法测定地耳草中槲皮素的含量[J].中国中药杂志,2004,29(5)：476-478
[30]王永刚,苏薇薇,梁少玲.利用不同型号大孔树脂对田基黄水提成分进行分离[J].中药材,2007,30(12)：1537-1539
[31]彭维,吴钉红,杨立伟,等.田基黄药材的质量研究[J].中南药学,2006,4(5)：340-342
[32]韩乐,宋健平,刘训红,等.地耳草黄酮类成分分析[J].中国药学杂志,2011,46(7)：542-545
[33]韩乐,宋健平,刘训红,等.地耳草黄酮类成分分析及其动态研究[J].南京中医药大学学报,2011,27(2)：165-168
[34]唐丹,张琳,田景奎.分光光度法测定田基黄中黄酮的含量[J].中国现代应用药学杂志,2007,24(7)：620-622
[35]秦盛莹,陈晓辉,米丹,等RP-HPLC法测定田基黄中异巴西红厚壳素的含量[J].药物分析杂志,2007,27(5)：718-720
[36]韩乐,刘训红,王丽娟,等.地耳草挥发性成分的HSGC-MS分析[J].中国药师,2010,13(6)：770-773
[37]韩乐,刘训红,王丽娟,等.地耳草挥发性成分HSGC/MS分析及其动态研究[J].质 谱学报,2010,31(4)：142-146
[38]祝兴勇,杨群,陶静.HPLC测定田基黄胶囊中槲皮素含量探讨[J].九江学院学报(自然科学版),2005,4,60-61
[39]虞金宝,吕武清,李才堂,等.HPLC测定田基黄注射液中槲皮素含量[J].中成药,2005,27(1)：100-101.
[40]王永刚,杨立伟,苏薇薇.田基黄药材指纹图谱研究[J].南方医科大学学报,2006,26(7)：1001-1002.
[41]吴忠,杨立伟,王永刚,等.田基黄注射液HPLC指纹图谱研究[J].中药材,2004,27(6)：441-442.
[42]苏薇薇,杨立伟,王永刚.利用指纹图谱技术监控田基黄注射液的生产过程[J].中药材,2004,27(9)：672-673
[43]韩乐,刘训红,王丽娟,等.地耳草HSGC-MS(?)旨纹图谱的研究[J].现代中药研究与实践,2011,25(1)：22-24
[44]陈丽云,杨立伟,苏薇薇,等.田基黄及其注射液的研究进展[J].中药材,2002,25(7)：525-528
[45]孙忠义,黎七雄.田基黄治疗原发性肝癌30例[J].中西医结合肝炎病杂志,1995,5(4)：29-30
[46]Leuscher J.2nd International Congress on Phytomedicine and 7th Congress of the German Society of Phytotherapy, September 11-14 1996, Munich, Germany, SL-80
[47]Wheatly D.2nd International Congress on Phytomedicine and 7th Congress of the German Society of Phytotherapy, September 11-14 1996, Munich, Germany, SL-86
[48]陈厚平,肖新成.田基黄茶治疗高脂血症的疗效观察[J].中国医药导报,2006,3(30)：92