痰热清注射液体内代谢与相互作用研究
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摘要
中药注射液是中医药在长期发展的基础上形成的一种新剂型，由于其自身特点，中药注射液成分复杂，临床适应症较多，在发展过程中也出现过一些影响重大的不良反应事件。一些中药注射液的质量标准落后，缺乏控制其质量稳定性的评价指标，物质研究基础不足；药物进入体内的入血成分不明确，药动学特征不够清晰，药物之间相互作用研究并不多见。这些不足大大影响了中药注射液在临床的安全有效应用，难以适应中药现代化要求，因此提高中药注射液的质量标准与用药安全性势在必行。
痰热清注射液由黄芩、熊胆粉、山羊角、金银花和连翘组成，主要用于风温肺热病痰热阻肺证，是治疗急性支气管炎和急性肺炎等疾病的中药制剂，被广泛应用于呼吸科、儿科、外科、肿瘤科等。目前痰热清注射液缺少权威的质量控制体系，其体内过程也并不清楚，对其它药物的疑似影响也有报道。因此本文以痰热清注射液为研究对象，以HPLC、LC-MS/MS、LC-Q-TOF/MS联用技术为主要监测手段，在对痰热清注射液质量控制研究和痰热清注射液主要成分及西罗莫司体内定性定量分析方法建立的基础上，深入探讨痰热清注射液体内代谢动力学特征和及与西罗莫司的相互作用机制，具体内容包括：
1、采用HPLC-DAD-ELSD技术对11批不同批次的痰热清注射液建立了双谱指纹图谱，并进行了相似度分析。在此基础上以LC-Q-TOF/MS技术对痰热清注射液的化学成分进行了鉴别，共鉴别出53种化合物，并根据二级质谱特征离子区分了部分同分异构体，同时对指纹图谱的部分峰进行了指认，使其代表性增强。对痰热清注射液中的主要成分绿原酸、咖啡酸、黄芩苷、熊去氧胆酸与鹅去氧胆酸建立了HPLC-DAD-ELSD含量测定方法，并进行了方法学考察。结果表明各成分线性关系良好（r>0.99），日内、日间精密度均小于5%，重现性好，精密度高，成功用于不同批次痰热清注射液的测定，为更好地控制痰热清注射液质量提供了科学依据，并为体内药代动力学研究所需的质量稳定可靠的供试样品提供了保证。
2、采用LC-Q-TOF/MS技术对痰热清注射液的入血成分进行了鉴定，共鉴别出20余种入血成分。再采用LC-MS/MS技术建立了对痰热清注射液中5种主要活性成分，即绿原酸、咖啡酸、黄芩苷、熊去氧胆酸与鹅去氧胆酸，在大鼠血浆中的定量分析方法。采用蛋白沉淀为血浆样品前处理条件，沉淀剂为甲醇：乙腈＝3：1，以芦丁、葛根素为内标，色谱分析采用Zorbax SB-C18柱(3.5μm，100mm×2.1mm)，流动相为乙腈与水（含0.1%甲酸），采用梯度洗脱，流速为0.3mL·min(-1)，柱温为35℃。运用Agilent G6410A型串联质谱的多反应监测(MRM)模式负离子检测，并进行了系统的方法学评价。结果显示，在各自的生物样品浓度范围内，均呈良好线性，r>0.99；各成分的线性范围分别为：30～14933ng·mL(-1)，27～13333ng·mL(-1)，50～50333ng·mL(-1)，550～55000ng·mL(-1)，480～48000ng·mL(-1)，日内、日间精密度均小于14%，提取回收率在70%～105%之间。该方法操作简单，选择性好，灵敏度高，成功用于痰热清注射液大鼠血浆的药代动力学研究，为临床合理用药提供参考依据。最后以LC-Q-TOF/MS技术对痰热清注射液主要入血成分的代谢产物进行了初步鉴别，初步明确了痰热清注射液在体内的代谢特征。
3、本章建立了一种简单、快速、灵敏的LC-MS/MS方法来测定大鼠全血中西罗莫司的浓度。蛋白沉淀法可有效提取全血中的西罗莫司，内源性杂质不干扰测定，标准曲线线性关系良好（r>0.99），最低定量限为2.5ng·mL(-1)，高、中、低3个浓度下测得各成分的日内和日间精密度RSD均低于15%，相对回收率、绝对回收率均符合要求。本方法各项指标符合生物样品分析测定要求，且操作简单，选择性好，灵敏度高，适用于痰热清注射液与西罗莫司合并用药后的药代动力学研究。从整体药代动力学角度上考察了在不同时间注射等量痰热清注射液及在相同时间注射不同剂量痰热清注射液对西罗莫司在大鼠体内过程的影响，结果显示痰热清注射液在体内对西罗莫司都表现为Cmax升高，AUC0→t增大，对其消除相并没有明显影响。
4、采用人肝微粒体体外孵育实验，系统考察了痰热清注射液及5个主要活性成分对CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP3A4和CYP2E1这6种酶活性是否产生抑制作用，从而影响西罗莫司在肝微粒体的代谢。并以正己烷、二氯甲烷、乙酸乙酯及水对痰热清注射液进行了液液萃取，再以指纹图谱的液相条件为基础，以不同时间间隔对痰热清注射液进行了分段收集。结果显示，痰热清注射液对这6种酶均有不同程度的抑制作用，但其5个主要成分及除水提液外的其它萃取液无明显抑制，而痰热清注射液0-5min段和30min以后的两段收集液有不同程度的抑制作用。初步证实了痰热清注射液是通过抑制CYP450酶系从而抑制西罗莫司的代谢使其生物利用度升高，但具体抑制性成分仍有待考察。
TCM injection is a totally new dosage formation based on its long development,due to its specific characters like complicated constituents, wide therapeutic index, wehave met some serious adverse occasions. The present research background for the TCMis the quality control standards can't match up with the current requirements, we alsodon't have a target index to make sure the reproducibility of quality control, the basicelements of TCM hadn't drawn great attention from the researchers. What's more, theeffective ingredients and pharmacokinetic characters of drugs administrated in humanplasma are still unclear, we even can't get much report about TCM' drug-drug interactionwith other chemotherapy, all those drawbacks affect badly on the successful clinicalapplication of the TCM injection, which can't keep up with the pace of the Modernizationof TCM, so it's essential to improve the quality control of TCM injection and make suresafe drug administration.
TRQ injection, consisting of scutellaria, pulvis ellis urs, cornu gorais, and lonicerajaponica, forsythia suspense, is targeting for lung fever syndrome and widely used astreatment for acute bronchitis, acute pneumonia in respiratory department, pediatricdepartment, surgical department, oncology department. To date there is no official qualitycontrol system for TRQ injection, we get few knowledge about its metabolism in vivo,and several repots had talked about its interaction with other chemotherapy. In this article,we took TRQ injection as the research target, via the monitor equipment such as HPLC,LC-MS/MS and LC-Q-TOF/MS, we have done some quality study of TRQ andsuccessfully determined5major components of TRQ injections, sirolimus respectively.Meanwhile, we processed further pharmacokinetic investigation of TRQ injection in vivoand its interaction with sirolimus, the detailed contents are as follow:
1. We got fingerprints of11different batches of TRQ injection viaHPLC-DAD-ELSD, and finished the relative analysis, and also successfully identified53components by LC-Q-TOF/MS, and according to the specific product ion fragments, wehad distinguished some isomers, which made the fingerprints more representative. Forthe5major constituents(chlorogenic acid, caffeic acid, baicalin, ursodesoxycholic acid)of TRQ injections, a sensitive HPLC-DAD-ELSD determination method was proposed, we also validated the method, the result was satisfactory, with a calibration coefficientr2>0.99, both intra-day precision and inter-day precision below5%. We have successfullyapplied this method for determination of other TRQ injection batches. The work beforegave support for the quality control of TRQ injection and we could make sure the qualityof TRQ injection involved in the following pharmacokinetic study was stable andacceptable.
2. We have identified more than20ingredients of TRQ injection admistrated intoplasma via LC-Q-TOF/MS technique. Then a LC-MS/MS method for simultaneousdetermination of5major constituents(chlorogenic acid, caffeic acid, baicalin,ursodesoxycholic acid, chenodeoxycholic acid) in mouss plasma was provided, we choseprotein precipitation as pretreatment condition, and the reagent was methanol:acetonitrile(3:1, v/v), rutin and puerarin were used as internal standard, we performed thechromatographic separation through a Zorbax SB-C18column(3.5μm,100mm×2.1mm)with gradient elution of acetonitrile and0.1%formic acid in water, the flow rate was0.3mL·min(-1), and column temperature was set at35oC. We chose MRM as the monitoringmode. The whole method was successfully validated, the calibration cure range was30(-1)4933ng·mL(-1),27(-1)3333ng·mL(-1),50-5033ng·mL(-1),550-55000ng·mL(-1),480-48000ng·mL(-1), for chlorogenic acid, caffeic acid, baicalin, ursodesoxycholic acid,chenodeoxycholic acid respectively. Both intra-day and inter-day precision were below14%, the recovery percentage ranged from70%(-1)05%. Altogether, this simple, specificand sensitive method successfully applied to pharmacokinetic study of TRQ injection,provided support for clinical therapy. Finally we primarily identified the constituents ofTRQ injection administrated via LC-Q-TOF/MS, gained some knowledge of itsmetabolism character in vivo.
3. In this article, we proposed a simple, rapid, sensitive method for determinationsirolimus in mouse plasma. Protein precipitation can extract the sirolimus in whole bloodeffectively and eliminated the matrix effect. The results showed that coefficient r2wasmore than0.99of calibration curve, LOQ proved to be2.5ng·mL(-1), other parameterssuch as intra-day and inter-day precision were below15%, recovery test was alsosatisfactory. This method matched all the needs for quantitative analysis of biologicalsample, and was simple, specific, and sensitive, which can be suited for thepharmacokinetic study of TRQ injection combined with sirolimous administration. Forthe whole part of pharmacokinetic study, we had studied that the same amount of TRQ injection could affect sirolimus metabolism at different time, and the different amounts ofTRQ injection could affect sirolimus metabolism at the same time, the result suggestedthat TRQ injection promoted the Cmax, followed by the increase of AUC0-t, however itdidn't seem to change sirolimus's elimination in vivo.
4. Via the liver microsomal incubation experiments in vitro, we had systematicallystudied whether TRQ injection and its5major constituents inhibited the activity ofCYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4and CYP2E1, thus affecting themetabolism of sirolimous in liver microsomal. The results indicated TRQ injectionaffected those6enzymes at some extent, but the5definited constituents didn't work.Subsequently we selected liquid-liquid extraction as the pretreatment procedure, andreagents such as n-hexane, dichloromethane, acetate and water had been tested. We foundthat only water extracts inhibited the activity of enzymes, which indicated that inhibitionconstituents are strongly polar. The experiments validated that TRQ injection canimprove the bioavailability of sirolimus by inhibiting the activity of the CYP450enzymefamily, but the exact worked constituents still needed further investigation.
痰热清注射液由黄芩、熊胆粉、山羊角、金银花和连翘组成，主要用于风温肺热病痰热阻肺证，是治疗急性支气管炎和急性肺炎等疾病的中药制剂，被广泛应用于呼吸科、儿科、外科、肿瘤科等。目前痰热清注射液缺少权威的质量控制体系，其体内过程也并不清楚，对其它药物的疑似影响也有报道。因此本文以痰热清注射液为研究对象，以HPLC、LC-MS/MS、LC-Q-TOF/MS联用技术为主要监测手段，在对痰热清注射液质量控制研究和痰热清注射液主要成分及西罗莫司体内定性定量分析方法建立的基础上，深入探讨痰热清注射液体内代谢动力学特征和及与西罗莫司的相互作用机制，具体内容包括：
1、采用HPLC-DAD-ELSD技术对11批不同批次的痰热清注射液建立了双谱指纹图谱，并进行了相似度分析。在此基础上以LC-Q-TOF/MS技术对痰热清注射液的化学成分进行了鉴别，共鉴别出53种化合物，并根据二级质谱特征离子区分了部分同分异构体，同时对指纹图谱的部分峰进行了指认，使其代表性增强。对痰热清注射液中的主要成分绿原酸、咖啡酸、黄芩苷、熊去氧胆酸与鹅去氧胆酸建立了HPLC-DAD-ELSD含量测定方法，并进行了方法学考察。结果表明各成分线性关系良好（r>0.99），日内、日间精密度均小于5%，重现性好，精密度高，成功用于不同批次痰热清注射液的测定，为更好地控制痰热清注射液质量提供了科学依据，并为体内药代动力学研究所需的质量稳定可靠的供试样品提供了保证。
2、采用LC-Q-TOF/MS技术对痰热清注射液的入血成分进行了鉴定，共鉴别出20余种入血成分。再采用LC-MS/MS技术建立了对痰热清注射液中5种主要活性成分，即绿原酸、咖啡酸、黄芩苷、熊去氧胆酸与鹅去氧胆酸，在大鼠血浆中的定量分析方法。采用蛋白沉淀为血浆样品前处理条件，沉淀剂为甲醇：乙腈＝3：1，以芦丁、葛根素为内标，色谱分析采用Zorbax SB-C18柱(3.5μm，100mm×2.1mm)，流动相为乙腈与水（含0.1%甲酸），采用梯度洗脱，流速为0.3mL·min(-1)，柱温为35℃。运用Agilent G6410A型串联质谱的多反应监测(MRM)模式负离子检测，并进行了系统的方法学评价。结果显示，在各自的生物样品浓度范围内，均呈良好线性，r>0.99；各成分的线性范围分别为：30～14933ng·mL(-1)，27～13333ng·mL(-1)，50～50333ng·mL(-1)，550～55000ng·mL(-1)，480～48000ng·mL(-1)，日内、日间精密度均小于14%，提取回收率在70%～105%之间。该方法操作简单，选择性好，灵敏度高，成功用于痰热清注射液大鼠血浆的药代动力学研究，为临床合理用药提供参考依据。最后以LC-Q-TOF/MS技术对痰热清注射液主要入血成分的代谢产物进行了初步鉴别，初步明确了痰热清注射液在体内的代谢特征。
3、本章建立了一种简单、快速、灵敏的LC-MS/MS方法来测定大鼠全血中西罗莫司的浓度。蛋白沉淀法可有效提取全血中的西罗莫司，内源性杂质不干扰测定，标准曲线线性关系良好（r>0.99），最低定量限为2.5ng·mL(-1)，高、中、低3个浓度下测得各成分的日内和日间精密度RSD均低于15%，相对回收率、绝对回收率均符合要求。本方法各项指标符合生物样品分析测定要求，且操作简单，选择性好，灵敏度高，适用于痰热清注射液与西罗莫司合并用药后的药代动力学研究。从整体药代动力学角度上考察了在不同时间注射等量痰热清注射液及在相同时间注射不同剂量痰热清注射液对西罗莫司在大鼠体内过程的影响，结果显示痰热清注射液在体内对西罗莫司都表现为Cmax升高，AUC0→t增大，对其消除相并没有明显影响。
4、采用人肝微粒体体外孵育实验，系统考察了痰热清注射液及5个主要活性成分对CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP3A4和CYP2E1这6种酶活性是否产生抑制作用，从而影响西罗莫司在肝微粒体的代谢。并以正己烷、二氯甲烷、乙酸乙酯及水对痰热清注射液进行了液液萃取，再以指纹图谱的液相条件为基础，以不同时间间隔对痰热清注射液进行了分段收集。结果显示，痰热清注射液对这6种酶均有不同程度的抑制作用，但其5个主要成分及除水提液外的其它萃取液无明显抑制，而痰热清注射液0-5min段和30min以后的两段收集液有不同程度的抑制作用。初步证实了痰热清注射液是通过抑制CYP450酶系从而抑制西罗莫司的代谢使其生物利用度升高，但具体抑制性成分仍有待考察。
TCM injection is a totally new dosage formation based on its long development,due to its specific characters like complicated constituents, wide therapeutic index, wehave met some serious adverse occasions. The present research background for the TCMis the quality control standards can't match up with the current requirements, we alsodon't have a target index to make sure the reproducibility of quality control, the basicelements of TCM hadn't drawn great attention from the researchers. What's more, theeffective ingredients and pharmacokinetic characters of drugs administrated in humanplasma are still unclear, we even can't get much report about TCM' drug-drug interactionwith other chemotherapy, all those drawbacks affect badly on the successful clinicalapplication of the TCM injection, which can't keep up with the pace of the Modernizationof TCM, so it's essential to improve the quality control of TCM injection and make suresafe drug administration.
TRQ injection, consisting of scutellaria, pulvis ellis urs, cornu gorais, and lonicerajaponica, forsythia suspense, is targeting for lung fever syndrome and widely used astreatment for acute bronchitis, acute pneumonia in respiratory department, pediatricdepartment, surgical department, oncology department. To date there is no official qualitycontrol system for TRQ injection, we get few knowledge about its metabolism in vivo,and several repots had talked about its interaction with other chemotherapy. In this article,we took TRQ injection as the research target, via the monitor equipment such as HPLC,LC-MS/MS and LC-Q-TOF/MS, we have done some quality study of TRQ andsuccessfully determined5major components of TRQ injections, sirolimus respectively.Meanwhile, we processed further pharmacokinetic investigation of TRQ injection in vivoand its interaction with sirolimus, the detailed contents are as follow:
1. We got fingerprints of11different batches of TRQ injection viaHPLC-DAD-ELSD, and finished the relative analysis, and also successfully identified53components by LC-Q-TOF/MS, and according to the specific product ion fragments, wehad distinguished some isomers, which made the fingerprints more representative. Forthe5major constituents(chlorogenic acid, caffeic acid, baicalin, ursodesoxycholic acid)of TRQ injections, a sensitive HPLC-DAD-ELSD determination method was proposed, we also validated the method, the result was satisfactory, with a calibration coefficientr2>0.99, both intra-day precision and inter-day precision below5%. We have successfullyapplied this method for determination of other TRQ injection batches. The work beforegave support for the quality control of TRQ injection and we could make sure the qualityof TRQ injection involved in the following pharmacokinetic study was stable andacceptable.
2. We have identified more than20ingredients of TRQ injection admistrated intoplasma via LC-Q-TOF/MS technique. Then a LC-MS/MS method for simultaneousdetermination of5major constituents(chlorogenic acid, caffeic acid, baicalin,ursodesoxycholic acid, chenodeoxycholic acid) in mouss plasma was provided, we choseprotein precipitation as pretreatment condition, and the reagent was methanol:acetonitrile(3:1, v/v), rutin and puerarin were used as internal standard, we performed thechromatographic separation through a Zorbax SB-C18column(3.5μm,100mm×2.1mm)with gradient elution of acetonitrile and0.1%formic acid in water, the flow rate was0.3mL·min(-1), and column temperature was set at35oC. We chose MRM as the monitoringmode. The whole method was successfully validated, the calibration cure range was30(-1)4933ng·mL(-1),27(-1)3333ng·mL(-1),50-5033ng·mL(-1),550-55000ng·mL(-1),480-48000ng·mL(-1), for chlorogenic acid, caffeic acid, baicalin, ursodesoxycholic acid,chenodeoxycholic acid respectively. Both intra-day and inter-day precision were below14%, the recovery percentage ranged from70%(-1)05%. Altogether, this simple, specificand sensitive method successfully applied to pharmacokinetic study of TRQ injection,provided support for clinical therapy. Finally we primarily identified the constituents ofTRQ injection administrated via LC-Q-TOF/MS, gained some knowledge of itsmetabolism character in vivo.
3. In this article, we proposed a simple, rapid, sensitive method for determinationsirolimus in mouse plasma. Protein precipitation can extract the sirolimus in whole bloodeffectively and eliminated the matrix effect. The results showed that coefficient r2wasmore than0.99of calibration curve, LOQ proved to be2.5ng·mL(-1), other parameterssuch as intra-day and inter-day precision were below15%, recovery test was alsosatisfactory. This method matched all the needs for quantitative analysis of biologicalsample, and was simple, specific, and sensitive, which can be suited for thepharmacokinetic study of TRQ injection combined with sirolimous administration. Forthe whole part of pharmacokinetic study, we had studied that the same amount of TRQ injection could affect sirolimus metabolism at different time, and the different amounts ofTRQ injection could affect sirolimus metabolism at the same time, the result suggestedthat TRQ injection promoted the Cmax, followed by the increase of AUC0-t, however itdidn't seem to change sirolimus's elimination in vivo.
4. Via the liver microsomal incubation experiments in vitro, we had systematicallystudied whether TRQ injection and its5major constituents inhibited the activity ofCYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4and CYP2E1, thus affecting themetabolism of sirolimous in liver microsomal. The results indicated TRQ injectionaffected those6enzymes at some extent, but the5definited constituents didn't work.Subsequently we selected liquid-liquid extraction as the pretreatment procedure, andreagents such as n-hexane, dichloromethane, acetate and water had been tested. We foundthat only water extracts inhibited the activity of enzymes, which indicated that inhibitionconstituents are strongly polar. The experiments validated that TRQ injection canimprove the bioavailability of sirolimus by inhibiting the activity of the CYP450enzymefamily, but the exact worked constituents still needed further investigation.
引文
[1]宋柳全，高兴华．痰热清注射液治疗急性肺炎的疗效观察．中国医药导报，2011，8(23)：88-89.
[2]李庆范．痰热清注射液治疗小儿肺炎的临床疗效分析．中外医疗，2011，30(20)：127-127.
[3]王界成．痰热清注射液治疗上呼吸道感染发热62例．中国中医急症2011，20(6)：959-959.
[4]白晓黎．痰热清注射液治疗成人上呼吸道感染疗效观察．中国实用医刊，2011，38(10)：98-98.
[5]宋志香，李刘坤，李兴广．中药痰热清注射液治疗MRSA感染性肺炎的临床观察研究．中华医院感染学杂志，2010(11)：1596-1598.
[6]李文，毛兵，王刚，王蕾，常静，张颖，万美华，郭佳，郑玉琼．Effect of Tanreqing Injection（痰热清注射液）on Treatment of Acute Exacerbation of Chronic Obstructive PulmonaryDisease with Chinese Medicine Syndrome of Retention of Phlegm and Heat in Fei（肺）.中国结合医学杂志：英文版，2010(2)：131-137.
[7]石珂．痰热清注射液治疗下呼吸道感染临床观察．中国医药指南，2010(14)：60-61.
[8]宿向东，郭鹏，董艳，痰热清注射液治疗恶性肿瘤并发感染52例．中国中医急症，2007，16(3)：353-354.
[9]吴伟明，陈丽佳，诸乐恺．高效液相色谱法测定痰热清注射液中黄芩苷和绿原酸的含量．儿科药学杂志，2006，12(4)：38-40.
[10]黄其春，涂文升．HPLC法测定痰热清注射液中黄芩苷的含量．中国药房2008，19（30）：2388-2389
[11]姚文冰．HPLC法测定痰热清注射液中黄芩苷和连翘苷的含量．中国药师，2011，14(10)：1479-1480
[12] Dongmei Yan, Yingbao Yang, Sinya Uchida, Shingen Misaka, Jinghui Luo, Kazuhiko Takeuchi,Naoki Inui, Shizuo Yamada, Kyoichi Ohashi, Hiroshi Watanabe, Effects of ursodeoxycholic acidon the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam in healthyvolunteers, Naunyn-Schmiedeberg’s Arch Pharmacol.2008(377):629–636
[13] Peng-Fei Yue, Wen-Jin Zhang, Hai-Long Yuan, Ming Yang, Wei-Feng Zhu, Pei-Lie Cai andXiao-He Xiao, Process Optimization, Characterization and Pharmacokinetic Evaluation in Ratsof Ursodeoxycholic Acid–Phospholipid Complex, AAPS PharmSciTech,2008(9):326-332
[14]罗立宇，刘洋，石任兵，姜艳艳，方敏，韩一方．黄芩中黄酮类化学成分代谢研究进展．国际中医中药杂志，2010，32(4)：359-361
[15]董毅．正品黄芩与甘肃黄芩有效化学成分及抑菌作用的比较研究．中国中医药科技，2010(3)：226-228.
[16]李艳荣，潘海峰，魏红，李守拙．中药材黄芩的研究近况．承德医学院学报，2009，26(4)：418-420
[17]刘英学，刘中刚，苏兰，杨芮平，郝东方，裴月湖．黄芩化学成分研究．中国药物化学杂志，2009，19(1)：59-62．
[18]王丽景，姜逸，常晨．黄芩的药理作用及其主要成分的鉴定与检测．中国禽业导刊，2007，24(16)：46-46．
[19]周锡钦，梁鸿，路新华，蔡少青，王分邠，赵玉英．中药黄芩主要黄酮类成分及其生物活性研究．北京大学学报：医学版，2009，41(5)：578-584．
[20]姜健，杨宝灵，李慧，苏明，姜国斌．黄芩中黄酮类化合物的定性与定量分析．安徽农业科学，2009，37(31)：15238-15240．
[21]曹岗，邵玉蓝，金奇．黄芩活性成分提取分离研究进展．抗感染药学，2009，6(2)：87-91．
[22]金敏．黄芩中黄酮类化学成分研究进展．中国民族医药杂志，2008，14(9)：55-56．
[23]郭继芬，陈四平，乔善义，杨明，赵毅民．黄芩总黄酮提取物的HPLC-MS/MS分析．药物分析杂志，2005，25(3)：267-269．
[24]宋磊，沈伟，于昕．金银花研究新进展．按摩与康复医学，2010，1(35)：34-35．
[25]陈永新，李峰，周正礼，冯帅，王文炳．金银花脂溶性成分的气相色谱-质谱分析．中国中医药信息杂志，2010，17(9)：37-38．
[26]陈秋竹，林瑞超，王钢力，李发美．金银花提取物化学成分研究．中药材，2010(6)：920-922．
[27]宋兴良，吕莉．金银花中挥发性成分的GC/MS分析及其指纹图谱的建立．临沂师范学院学报，2010(3)：96-100．
[28]朱祥英，付宇飞，潘再法，王丽丽．金银花挥发性成分的HS-SPME-GC/MS研究．分析化学，2009，37(A02)：289-289．
[29]周建玉．金银花中化学成分分析研究进展．天津药学，2009，21(5)：60-62．
[30]隋慧颖．金银花化学成分及其在药理学中的应用研究．黑龙江科技信息，2009(9)：159-159．
[31]王力川．金银花的化学成分及功效研究进展．安徽农业科学，2009，37(5)：2036-2037．
[32]吴晓春，杨苏亚．金银花的成分及药理作用分析．青海医药杂志，2007(5)：88-89．
[33]贺伟．金银花的化学成分及药理作用研究．中国医药导报，2007，4(08X)：8-9．
[34]赵琰玲，尹莲．金银花化学成分与有效成分提取研究进展．医药导报，2007，26(5)：521-523．
[35]毕跃峰，田野，裴姗姗，张聪，刘宏民．金银花化学成分分析．郑州大学学报：理学版，2007，39(2)：184-186．
[36]陈永新，李峰，周正礼，冯帅，王文炳．金银花脂溶性成分的气相色谱-质谱分析．中国中医药信息杂志，2010，17(9)：37-38．
[37]湛雪辉，徐光伟，李飞，李晓如，周随安，曹芬，李侠．Comparative analysis of volatileconstituents between herbal pairflos lonicerae-caulis lonicerae and its single herbs．中南大学学报：英文版，2010，17(4)：726-731．
[38]宋兴良，吕莉．金银花中挥发性成分的GC/MS分析及其指纹图谱的建立．临沂师范学院学报，2010(3)：96-100．
[39]林凯．福建金银花挥发油成分分析．江西农业学报，2009，21(5)：102-104．
[40]王艳萍，薛兴亚，章飞芳，梁鑫淼．正相液相-气相-质谱联用技术分离分析金银花挥发油化学成分．世界科学技术：中医药现代化，2008，10(6)：45-55．
[41]朴香兰，田燕泽．连翘木脂素类成分研究现状．时珍国医国药，2010，21(8)：2021-2023．
[42]欧阳辉，谢丽艳，黄小方，罗莎，杨世林．贯叶连翘的化学成分与药理研究进展及前景展望．江西中医药，2010(7)：78-80．
[43]段文娟，耿岩玲，祝贺，林云良，王晓，刘建华．中药连翘化学成分和分析方法的研究进展．山东科学，2010，23(2)：33-37，66．
[44]肖君．贯叶连翘的研究分析．中国中医药咨讯，2009，1(5)：11-11．
[45]邢学锋，陈飞龙，罗佳波．金银花、连翘药对配伍挥发油成分的GC-MS分析．中药新药与临床药理，2009，20(4)：358-360．
[46]简永耀，靳龙文．连翘的化学成分及药理学研究．淮海医药，2009，27(4)：349-350．
[47]吴晶晶，何宇新，李玲．贯叶连翘的研究进展．时珍国医国药，2009，20(2)：404-405．
[48]高颖，胡冬华．贯叶连翘提取物的药理活性及化学研究．长春中医药大学学报，2008，24(6)：667-668．
[49]方颖，邹国安，刘焱文．连翘的化学成分．中国天然药物，2008，6(3)：235-236．
[50]王金梅，许启泰，康文艺．连翘化学成分及药理研究进展．天然产物研究与开发，2007，19(B05)：153-157．
[51]李艳，曹学丽，付鹏．贯叶连翘的化学成分及其提取方法研究进展．北京工商大学学报：自然科学版，2007，25(6)：6-10．
[52]吕英刚，刘世安，吴敏菊，张金荣，杜媛媛．山东贯叶连翘挥发油成分分析．中国中医药信息杂志，2007，14(8)：42-43．
[53]徐皓．贯叶连翘的化学成分及药理作用研究．安徽农业科学，2007，35(14)：4219-4221．
[54]王小芳，董晓宁，闫世才．贯叶连翘挥发性化学成分研究．西北植物学报，2006，26(6)：1259-1262．
[55]李倩．连翘的化学成分研究进展．河南中医学院学报，2005，20(2)：78-80．
[56]吴迎春，张尊听，甄宝勤，刘谦光．贯叶连翘化学成分分析．西北农林科技大学学报：自然科学版，2004，32(6)：99-100，106．
[57]吴敏，王霞，许平．贯叶连翘的研究进展．中成药，2004，26(9)：760-763．
[58]孟祥颖，郭良，杨明，李玉新．贯叶连翘挥发油成分的分析．分析化学，2003，31(6)：689-693．
[59]曾虹燕，周朴华．贯叶连翘挥发性成分分析．中药材，2000，23(12)：752-754．
[60]白洁，王冬梅，杨得坡．湖北小连翘中化学成分的高效液相色谱与电喷雾离子化质谱联用分析．武汉植物学研究，2008，26(1)：87-90．
[61]武建芳，路鑫，唐婉莹，孔宏伟，国旺．全二维气相色谱/飞行时间质谱用于连翘挥发油的研究．中国天然药物，2003，1(3)：150-154．
[62]刘力，胡嵘．山羊角研究概述．长春中医学院学报，1994，10(A02)：109-109．
[63]姜清华，翟延君．羚羊角与山羊角药理作用比较．山西医药杂志，2006，35(7)：582-583．
[64]张英杰，苑述刚，阮时宝，洪振丰．熊胆中药学及临床文献研究概述．辽宁中医药大学学报，2010，12(10)：107-108．
[65]罗强，陈全成，吴瑶，姜苗苗，陈志鸿，张晓坤，陈海峰．熊胆的化学成分研究．中国中药杂志，2010(18)：2416-2419．
[66]关晓燕，王熙惠，杨杰．熊胆汁的现状研究．当代医学，2009，15(18)：29-29．
[67]连常宝．熊胆粉的药理作用及临床应用研究概述．海峡药学，2008，20(8)：71-75．
[68]池述广．熊胆主要化学成分合成方法及药理研究进展．海峡药学，2008，20(2)：5-8．
[69]王丽影，高昕，佟子林，王喜军．熊胆的化学成分、药理作用及临床研究概况．中医药信息，2005，22(4)：30-33．
[70] Michael N. Clifford, Susan Knight, Nikolai Kuhnert, Discriminating between the six isomers ofdicaffeoylquinic acid by LC-MSn, Journal of agricultural and food chemistry,2005(53):3821-3832
[71] Wang Zheng, Michael. N. Clifford, Comparison of the profiles of chlorogenic acids and theirderivatives from three Chinese traditional herbs by LC-MSn, Acta Phamaceutica Sinica,2008(43):185-190
[72] Li BQ, Fu T, Dongyan Y, Mikovits JA, Ruscetti FW, Wang JM, Flavonoid baicalin inhibitsHIV-1infection at the level of viral entry, Biochemical and Biophysical ResearchCommunications,2000(276):534-538
[73] Liu IX，Durhan DG, Richards RM, Baicalin Synergy with β-Lactam Antibiotics AgainstMethicillin-resistant Staphylococcus aureus and Other β-Lactam-resistant Strains of S. aureus,Journal of Pharmacy and Pharmacology,2000(52):361-366
[74] Bao Qun Li, Tao Fu, Wang-Hua Gong, Nancy Dunlop, Hsiang-fu Kung, Yaodong Yan, JianKang, Ji Ming Wang, The flavonoid baicalin exhibits anti-inflammatory activity by binding tochemokines, Immunopharmacology,2000(49):295-306
[75] Yonggang Cao, Xiaoyuan Mao, Chunyan Sun, Ping Zheng, Jingquan Gao, Xiaorui Wang,Dongyu Min, Hongli Sun, Ni Xie, Jiqun Ca, Baicalin attenuates global cerebralischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathways, BrainResearch Bulletin,2011(85):396-402
[76] Chun-Ching Lin, Den-En Shieh, In Vivo Hepatoprotective Effect of Baicalein, Baicalin andWogonin from Scutellaria rivularis, Phytotherapy Research,1996(10):651-654
[77] May GR, Sutherland LR, Shaffer EA, Efficacy of bile acid therapy for gallstone dissolution: ameta-analysis of randomized trials, Alimentary Pharmacology&Therapeutics,1993(7):139-148
[78] Karthikesan K, Pari L, Menon VP, Antihyperlipidemic effect of chlorogenic acid andtetrahydrocurcumin in rats subjected to diabetogenic agents, Chemico-Biological Interactions,2010(188):643-650
[79] Hemmerle H, Burger HJ, Below P, Schubert G, Rippel R, Schindler PW, Paulus E, Herling AW,Herling, Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepaticglucose-6-phosphate translocase, Journal of Medicinal Chemistry,1997(40):137-145.
[80] Kwon HakCheol, Jung ChilMann, Shin ChaGyun, Lee JongKyo, Choi SangUn, Kim SunYeou,Lee KangRo, A new caffeoyl quinic acid from Aster scaber and its inhibitory activity againsthuman immunodeficiency virus-1(HIV-1) integrase, Journal Chemical&PharmaceuticalBulletin,2000(48):1796-1798
[81] Mee-Hyang Kweon, Han-Joon Hwang, Ha-Chin Sung, Identification and antioxidant activity ofnovel chlorogenic acid derivatives from bamboo(Phyllostachys edulis), Journal of Agriculturaland Food Chemistry,2001(49):4646-4655
[82] Gui-Feng Wang, Li-Ping Shi, Yu-Dan Ren, Qun-Fang Liu, Hou-Fu Liu, Ru-Jun Zhang, ZhuangLi, Feng-Hua Zhu, Pei-Lan He, Wei Tang, Pei-Zhen Tao, Chuan Li, Wei-Min Zhao, Jian-PingZuo, Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo andin vitro, Antiviral Research,2009(83):186-190
[83]钟敬华，侯晓蓉，范骁辉．化学指纹图谱类别相似性计算方法研究．中国中药杂志，2010，4(35):477-480
[84]詹雪艳，史新元，段天璇，李磊，乔延江．色谱指纹图谱组合相似度的算法．色谱，2010，28(11):1071-1076
[85]孙国祥，侯志飞，张春玲，毕开顺，孙毓庆．色谱指纹图谱定性相似度和定量相似度的比较研究．药学学报，2007，42(1)：75-80
[86] Kuhajda K., Kandrac J., Keresan S., Mikov M, Fawcett J.P., Structure and origin of bile acids:An overview, European Journal Of Drug Methabolism And Pharmacokinetics,2006,31(3):135-143
[87] Natalini, R. Sardella, E. Camaioni, S. Natalini, R. Pellicciari, Dominant Factors Affecting theChromatographic Behaviour of Bile Acids, Chromatographia2006,(64):343–349
[88] Jun Zhang, Min Chen, Wenzheng Ju, Shijia Liu, Meijuan Xu, Jihong Chu, Ting Wu, Liquidchromatograph/tandem mass spectrometry assay for the simultaneous determination ofchlorogenic acid and cinnamic acid in plasma and its application to a pharmacokinetic study,Journal of Pharmaceutical and Biomedical Analysis,2010(51):685–690
[89] T.H. Tsai, Y.F. Chen, A.Y.C. Shum, C.F. Chen, Determination of chlorogenic acid in rat bloodby microdialysis coupled with microbore liquid chromatography and its application topharmacokinetic studies, Journal of Chromatography A,2000(870):443-448
[90] S. J. Choi, C. K. Jeong I, H. M. Lee, K. Kim, K. S. DO, H. S. Lee, Simultaneous Determinationof Ursodeoxycholic Acid and Its Glycine-conjugate in Serum as Phenacyl Esters UsingMultidimensional Liquid Chromatography, Chromatographia1999,50(12):96-100
[91] Jun-Xiao Ye, Wang Wei, Li-Hui Quan, Chun-Yu Liu, Qi Chang, Yong-Hong Liao, AnLC-MS/MS method for the simultaneous determination of chlorogenic acid, forsythiaside A andbaicalin in rat plasma and its application to pharmacokinetic study of Shuang-huang-lian in rats,Journal of Pharmaceutical and Biomedical Analysis,2010(52):625-630
[92] Wei Qi, TingZhao, Wen-WenYang, Guang-HouWang, HuaYu,Hai-Xiao Zhao, ChenYang,Li-XinSun, Comparative pharmacokinetics of chlorogenic acid after oral administration in rats,Journal of Pharmaceutical Ananlysis,2011,1(4):270-274
[93] Rong Gao, Qiang Zheng, Tao Gong, Yao Fu, Li Deng, Zhi-Rong Zhang, Gradienthigh-performance liquid chromatography for the simultaneous determination of chlorogenic acidand baicalin in plasma and its application in the study of pharmacokinetics in rats, Journal ofPharmaceutical and Biomedical Analysis,2007(43):335-340
[94] Tong Lu, Jue Song, Fang Huang, Yuanxiong Deng, Lin Xie, Guangji Wang, Xiaodong Liu,Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radixscutellariae extract and Huang-Lian-Jie-Du-Tang to rats, Journal of Ethnopharmacology,2007(110):412-418
[95] Zi-chuan Zhang, Man Xu, Shi-feng Sun, Xue Qiao, Bao-rong Wang, Jian Han, De-an Guo,Metabolic analysis of four phenolic acids in rat by liquid chromatography-tandem massspectrometry, Journal of Chromatography B,2008(871):7-14
[96] Yuji Matsui, Shun Nakamura, Naoki Kondou, Yoshio Takasu,Ryuji Ochiai, YoshinoriMasukawa, Liquid chromatography-electrospray ionization-tandem mass spectrometry forsimultaneous analysis of chlorogenic acids and their metabolites in human plasma, Journal ofChromatography B,2007(858):96-105
[97] Andreas R., Rechner, Jeremy P.E. Spencer, Gunter Kuhnle, Ulrich Hahn, Catherine A.Rice-Evans, Novel biomarkers of the meatbolism of caffeic acid derivatives in vivo, Free RadicalBiology&Medicine,2001,30(11):1213-1222
[98] M.-P. Gonthier, C. Remesy, A. Scalbert, V. Cheynier, J.-M. Souquet, K. Poutanen, A.-M. Aura,Microbial metabolism of caffeic acid and its esters chlorogenic and caftaric acids by humanfaecal microbiota in vitro, Biomedicine&Pharmacotherapy,2006(60):536-540
[99] Vignot S., Faivre S., Aguirre D. mTOR-targeted therapy of eaneer with rapamycin derivatives.Ann Oncol,2005,16(4):525-537
[100] Jones K., Saadat-Lajevard S., Lee T., et al. An immuno-assay for the lneasurenlent ofsirolinms. Clin Ther,2000,22(suppl B):49-61
[101] Lam M.F., Yip T.P.S., Tse K.C., et al. Sirolimus in kidney transplantation: A pilot study inChinese patients. Hong Kong J Nephrol,2004,6(1):38-42
[102] Campanero M.A., Cardenas E., Sadaba B., et al.Therapeutic drug monitoring for sirolimusin whole blood of organ transplants by high-performance liquid chromatography with ultravioletdetection. J Chromatography A,2004,1031(1-2):265-273
[103] Rangan G.K., Nguyen T., Mainra R., et al. Therapeutic role of sirolimus in non-transplantkidney disease. Pharmacology&Therapeutics,2009,123(2):187-206
[104] Jiao Z, Shi X J, Li Z D, et al. Population pharmacokinetics of sirolimus in de nove Chineseadult renal transplant patients. Br J Clin Pharmacol,2009,68(1):47-60
[105] Macdonald A., Scarola J., Burke J.T., et al. Clinical pharmacokinetics and therapeutic drugmonitoring of sirolimus. Clin Ther,2000,22(suppl B):101-121
[106] Dansirikul C., Morris R.G., Tett S.E., et al. A bayesian approach for populationpharmacokinetic modeling of sirolimus. Br Clin Pharmacol,2006,62(4):420-434
[107]李海宏．痰热清注射液治疗术后并发坠积性肺炎疗效观察．医药产业资讯，2005，2(14)：73
[108] Kim H J, Chang E J, Cho S H, Chung S K, Park H D, Choi S W. Antioxidative activity ofresveratrol and its derivatives isolated from seeds of paeonia lactiflora, Biosci. Biotech. andBiochem.,2002(66):1990-1993
[109] Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., Protein measurement with thefolin phenol reagent, Journal of Biological Chemistry.1951(193):265-275
[110] Bjornsson TD, Callaghan JT, Einolf HJ, et al. Theconduct of in vitro and in vivo drug-druginteraction studies: a Ph RMA perspective, J Clin Pharmcol,2003(43):443-469
[111] Margolis JM, Obach RS. Impact of nonspecific binding to microsomes and phospholip id onthe inhibition of cytochrome P4502D6: imp lications for relating in vitro inhibition data to invivo drug interactions, Drug Metab Dispos,2003(31):606-611
[112] Tran TH, Von Moltke LL, Venkatakrishnan K, et al. Microsomal p rotein concentrationmodifies the apparent inhibitory potency of CYP3A inhibitors, Drug Metab Dispos,2002(30):1441-1445
[113]詹勤．桔梗在升陷汤中引经作用及其化学成分研究．第二军医大学博士论文，2012
[114]邸鹏．丹参酚酸类成分生源途径的探索及相关基因的克隆与功能研究．第二军医大学博士论文，2012
[115]杨琦．知母、黄柏及其药对标准提取物的质量控制研究．第二军医大学硕士论文，2009
[116]位华．五酯胶囊的药代动力学及与他克莫司相互作用研究．第二军医大学博士论文，2010
[117]蔡飞．滋肾丸药代动力学及其配伍机制研究．第二军医大学博士论文，2011
[118]张在丽，郭燕萍，李中东，施孝金，钟明康．西罗莫司胶囊在人体内的生物等效性评价．中国药学杂志，2012
[119]姜波．常用中成药对细胞色素P4503A4和P-糖蛋白的诱导研究．第二军医大学硕士论文，2010
[1]杨进周，韩凤琦，张伊辉．痰热清治疗麻疹合并肺部感染．Journal of Medical Forum，2006，27(17)：93．
[2]高雪，侯辉，曲敬来等．痰热清注射液治疗三种发热性病毒性急性上呼吸道感染的疗效观察．中国中西医结合耳鼻咽喉科杂志，2006，14(3)：171-173．
[3]陈淑玲，郝红．痰热清注射液治疗肺炎支原体肺炎30例临床观察．当代医药卫生，2005，2(8)：56-57．
[4]白留江，朱喜增．痰热清治疗腐生葡萄球菌肺炎30例疗效观察．社区医学杂志，2005，3(8)：4．
[5]马强．痰热清注射液治疗癌症发热64例疗效分析．中华腹部疾病杂志2004，4(8)：587
[6]彭桂兰．痰热清注射液治疗慢性支气管炎急性发作60例．当代医药卫生，2005，2(8)：28．
[7]杜家杰．痰热清注射液治疗上呼吸道感染疗效观察．中国实用医刊，2010，37(7)：92-93．
[8]张颖，唐丈容，张瑞明等．痰热清注射液治疗慢性支管炎急性发作的随机对照临床试验研究．中国现代实用医学杂志，2004，3(7)：21～23
[9]周庆伟，李素云，王海峰．痰热清注射液治疗急性下呼吸道感染300例．陕西中医，2005，26(4)：301～302
[10]冯彦刚，柳丽，李建华．痰热清注射液治疗小儿呼吸道感染46例疗效观察．中华医学理论与实践杂志，2003，3(12)：121
[11]熊旭东，赵敏．痰热清注射液治疗急性肺炎疗效研究(附60例临床对照观察)．中华中西医结合杂志，2003，3(10)：63
[12]熊旭东，周吉燕，曹康裕等．痰热清注射液治疗急性肺炎(痰热壅肺证)60例临床观察．中国中医急症，2003，12(2)：97-98
[13]扬松，张耀亭．痰热清注射液对肺结核辅助治疗的效果观察．临床肺科杂志，2007，12(1)：38-39．
[14]司丁，魏兆勇，陈如通．痰热清治疗病毒性肝炎退黄疗效观察．新乡医学院学报，2006，23(2)：193-194．
[15]杨跃杰．痰热清注射液治疗病毒性乙型肝炎疗效观察．中原医刊，2005，32(24)：76-77．
[16]陈怡发．痰热清注射液治疗急性胰腺炎的疗效观察．中原医刊，2005，32(14)：53．
[17]孙钩．痰热清治疗黄疸型肝炎32例．中华现代中西医杂志，2004，2(12)：1122
[18]田莉．痰热清治疗急性胆囊炎60例．第四军医大学学报，2005，26(6)：496．
[19]于友涛，杨光，申宝忠．痰热清注射液对原发性肝癌介入治疗的影响．实用肿瘤学杂志，2004，18(3)：177
[20]黄登鹏，彭卫平，陈少武等．痰热清注射液治疗重症急性胰腺炎抗炎作用观察．中国中医急症，2005，14(2)：117
[21]楚天舒，苗艳，梁艳等．痰热清注射液治疗绝经后妇女尿路感染48例．中医研究，2005，18(2)：36-37．
[22]楚天舒，苗艳，程银桢．痰热清注射液治疗肾盂肾炎32例．中医研究，2005，18(8)：40．
[23]闰爱国，许乐芬，刘刚等．痰热清注射液治疗肾综合症出血热疗效观察．中国药物与临床，2004，4(8)：601
[24]刘冠军，王合群，殷海燕．痰热清注射液治疗肾病综合征出血热发热期患者46例临床观察．中原医刊，2005，32(13)：46-47．
[25]周毅，何捷，刘勇．痰热清注射液治疗恶性肿瘤合并肺部感染疗效观察．中国中医急症，2005，14(1)：24
[26]史风锦，王守珍，徐丽霞．痰热清注射液治疗水痘疗效观察．中国中医急症，2006，15(2)：147．
[27]王江桥．痰热清注射液治疗急性脑卒中继发肺部感染18例临床观察．中原医刊，2005，32(1)：40
[28]陈玉清，李琳，张茵等．痰热清注射液治疗传染性单核细胞增多症24例．中医研究，2005，18(7)：45-46．
[29]韩小莉．痰热清注射液佐治川崎病21例疗效观察．中华综合医学杂志，2004，6(20)：2712
[30]刘红敏，乔秋杰，曹亚飞．中药痰热清注射液治疗急性风湿热疗效观察．中医正骨，2005，17(6)：16-17．
[31]许晓菲，痰热清注射液致不良反应文献分析．中国医药指南，2012，10（15）：409-411
[32]谢本树，张海英．痰热清致过敏性休克1例．中国药学杂志，2010，45(12)：918-919．
[33]张晋萍，冯宁宁．痰热清注射液致视物模糊1例．医药导报，2009，28(7)：915-916．
[34]张龙英．痰热清注射液致过敏性休克1例．医疗装备，2011，25(11)：51．
[35]蔡建英．痰热清与注射用乳糖酸阿奇霉素存在配伍禁忌．临床合理用药，2009，2(1)：11．
[36]崔桂英，刘婷．注射用白霉素与痰热清、炎琥宁之间的配伍禁忌．社区医学杂志，2006，4(12)：21．
[37]匡春艳．硫酸阿米卡星与痰热清可能存在配伍禁忌．山西医药杂志，2008，37(2)：110．
[38]申利萍，张雁雁．加替沙星与痰热清存在配伍禁忌．护理研究，2006，20(8)：2224．
[39]王秋月．疑痰热清注射液致过敏性休克1例．首都医药，2008，15(10)：45．
[40]李洪杰，张剑，程连房．痰热清注射液致过敏性休克1例．内蒙古中医药，2011，30(22)：34．
[41]张睿．头孢哌酮、痰热清与氢化考的松合用致小儿双硫仑样反应2例．中国实用医药，2010，5(3)：191
[42]薛东升，李小利，宋庆宏．痰热清注射液作用机理与临床应用．上海医药，2007
[43]李富善，黄晓玲．痰热清注射液的作用机理和临床应用．青海医药杂志，2011
[2]李庆范．痰热清注射液治疗小儿肺炎的临床疗效分析．中外医疗，2011，30(20)：127-127.
[3]王界成．痰热清注射液治疗上呼吸道感染发热62例．中国中医急症2011，20(6)：959-959.
[4]白晓黎．痰热清注射液治疗成人上呼吸道感染疗效观察．中国实用医刊，2011，38(10)：98-98.
[5]宋志香，李刘坤，李兴广．中药痰热清注射液治疗MRSA感染性肺炎的临床观察研究．中华医院感染学杂志，2010(11)：1596-1598.
[6]李文，毛兵，王刚，王蕾，常静，张颖，万美华，郭佳，郑玉琼．Effect of Tanreqing Injection（痰热清注射液）on Treatment of Acute Exacerbation of Chronic Obstructive PulmonaryDisease with Chinese Medicine Syndrome of Retention of Phlegm and Heat in Fei（肺）.中国结合医学杂志：英文版，2010(2)：131-137.
[7]石珂．痰热清注射液治疗下呼吸道感染临床观察．中国医药指南，2010(14)：60-61.
[8]宿向东，郭鹏，董艳，痰热清注射液治疗恶性肿瘤并发感染52例．中国中医急症，2007，16(3)：353-354.
[9]吴伟明，陈丽佳，诸乐恺．高效液相色谱法测定痰热清注射液中黄芩苷和绿原酸的含量．儿科药学杂志，2006，12(4)：38-40.
[10]黄其春，涂文升．HPLC法测定痰热清注射液中黄芩苷的含量．中国药房2008，19（30）：2388-2389
[11]姚文冰．HPLC法测定痰热清注射液中黄芩苷和连翘苷的含量．中国药师，2011，14(10)：1479-1480
[12] Dongmei Yan, Yingbao Yang, Sinya Uchida, Shingen Misaka, Jinghui Luo, Kazuhiko Takeuchi,Naoki Inui, Shizuo Yamada, Kyoichi Ohashi, Hiroshi Watanabe, Effects of ursodeoxycholic acidon the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam in healthyvolunteers, Naunyn-Schmiedeberg’s Arch Pharmacol.2008(377):629–636
[13] Peng-Fei Yue, Wen-Jin Zhang, Hai-Long Yuan, Ming Yang, Wei-Feng Zhu, Pei-Lie Cai andXiao-He Xiao, Process Optimization, Characterization and Pharmacokinetic Evaluation in Ratsof Ursodeoxycholic Acid–Phospholipid Complex, AAPS PharmSciTech,2008(9):326-332
[14]罗立宇，刘洋，石任兵，姜艳艳，方敏，韩一方．黄芩中黄酮类化学成分代谢研究进展．国际中医中药杂志，2010，32(4)：359-361
[15]董毅．正品黄芩与甘肃黄芩有效化学成分及抑菌作用的比较研究．中国中医药科技，2010(3)：226-228.
[16]李艳荣，潘海峰，魏红，李守拙．中药材黄芩的研究近况．承德医学院学报，2009，26(4)：418-420
[17]刘英学，刘中刚，苏兰，杨芮平，郝东方，裴月湖．黄芩化学成分研究．中国药物化学杂志，2009，19(1)：59-62．
[18]王丽景，姜逸，常晨．黄芩的药理作用及其主要成分的鉴定与检测．中国禽业导刊，2007，24(16)：46-46．
[19]周锡钦，梁鸿，路新华，蔡少青，王分邠，赵玉英．中药黄芩主要黄酮类成分及其生物活性研究．北京大学学报：医学版，2009，41(5)：578-584．
[20]姜健，杨宝灵，李慧，苏明，姜国斌．黄芩中黄酮类化合物的定性与定量分析．安徽农业科学，2009，37(31)：15238-15240．
[21]曹岗，邵玉蓝，金奇．黄芩活性成分提取分离研究进展．抗感染药学，2009，6(2)：87-91．
[22]金敏．黄芩中黄酮类化学成分研究进展．中国民族医药杂志，2008，14(9)：55-56．
[23]郭继芬，陈四平，乔善义，杨明，赵毅民．黄芩总黄酮提取物的HPLC-MS/MS分析．药物分析杂志，2005，25(3)：267-269．
[24]宋磊，沈伟，于昕．金银花研究新进展．按摩与康复医学，2010，1(35)：34-35．
[25]陈永新，李峰，周正礼，冯帅，王文炳．金银花脂溶性成分的气相色谱-质谱分析．中国中医药信息杂志，2010，17(9)：37-38．
[26]陈秋竹，林瑞超，王钢力，李发美．金银花提取物化学成分研究．中药材，2010(6)：920-922．
[27]宋兴良，吕莉．金银花中挥发性成分的GC/MS分析及其指纹图谱的建立．临沂师范学院学报，2010(3)：96-100．
[28]朱祥英，付宇飞，潘再法，王丽丽．金银花挥发性成分的HS-SPME-GC/MS研究．分析化学，2009，37(A02)：289-289．
[29]周建玉．金银花中化学成分分析研究进展．天津药学，2009，21(5)：60-62．
[30]隋慧颖．金银花化学成分及其在药理学中的应用研究．黑龙江科技信息，2009(9)：159-159．
[31]王力川．金银花的化学成分及功效研究进展．安徽农业科学，2009，37(5)：2036-2037．
[32]吴晓春，杨苏亚．金银花的成分及药理作用分析．青海医药杂志，2007(5)：88-89．
[33]贺伟．金银花的化学成分及药理作用研究．中国医药导报，2007，4(08X)：8-9．
[34]赵琰玲，尹莲．金银花化学成分与有效成分提取研究进展．医药导报，2007，26(5)：521-523．
[35]毕跃峰，田野，裴姗姗，张聪，刘宏民．金银花化学成分分析．郑州大学学报：理学版，2007，39(2)：184-186．
[36]陈永新，李峰，周正礼，冯帅，王文炳．金银花脂溶性成分的气相色谱-质谱分析．中国中医药信息杂志，2010，17(9)：37-38．
[37]湛雪辉，徐光伟，李飞，李晓如，周随安，曹芬，李侠．Comparative analysis of volatileconstituents between herbal pairflos lonicerae-caulis lonicerae and its single herbs．中南大学学报：英文版，2010，17(4)：726-731．
[38]宋兴良，吕莉．金银花中挥发性成分的GC/MS分析及其指纹图谱的建立．临沂师范学院学报，2010(3)：96-100．
[39]林凯．福建金银花挥发油成分分析．江西农业学报，2009，21(5)：102-104．
[40]王艳萍，薛兴亚，章飞芳，梁鑫淼．正相液相-气相-质谱联用技术分离分析金银花挥发油化学成分．世界科学技术：中医药现代化，2008，10(6)：45-55．
[41]朴香兰，田燕泽．连翘木脂素类成分研究现状．时珍国医国药，2010，21(8)：2021-2023．
[42]欧阳辉，谢丽艳，黄小方，罗莎，杨世林．贯叶连翘的化学成分与药理研究进展及前景展望．江西中医药，2010(7)：78-80．
[43]段文娟，耿岩玲，祝贺，林云良，王晓，刘建华．中药连翘化学成分和分析方法的研究进展．山东科学，2010，23(2)：33-37，66．
[44]肖君．贯叶连翘的研究分析．中国中医药咨讯，2009，1(5)：11-11．
[45]邢学锋，陈飞龙，罗佳波．金银花、连翘药对配伍挥发油成分的GC-MS分析．中药新药与临床药理，2009，20(4)：358-360．
[46]简永耀，靳龙文．连翘的化学成分及药理学研究．淮海医药，2009，27(4)：349-350．
[47]吴晶晶，何宇新，李玲．贯叶连翘的研究进展．时珍国医国药，2009，20(2)：404-405．
[48]高颖，胡冬华．贯叶连翘提取物的药理活性及化学研究．长春中医药大学学报，2008，24(6)：667-668．
[49]方颖，邹国安，刘焱文．连翘的化学成分．中国天然药物，2008，6(3)：235-236．
[50]王金梅，许启泰，康文艺．连翘化学成分及药理研究进展．天然产物研究与开发，2007，19(B05)：153-157．
[51]李艳，曹学丽，付鹏．贯叶连翘的化学成分及其提取方法研究进展．北京工商大学学报：自然科学版，2007，25(6)：6-10．
[52]吕英刚，刘世安，吴敏菊，张金荣，杜媛媛．山东贯叶连翘挥发油成分分析．中国中医药信息杂志，2007，14(8)：42-43．
[53]徐皓．贯叶连翘的化学成分及药理作用研究．安徽农业科学，2007，35(14)：4219-4221．
[54]王小芳，董晓宁，闫世才．贯叶连翘挥发性化学成分研究．西北植物学报，2006，26(6)：1259-1262．
[55]李倩．连翘的化学成分研究进展．河南中医学院学报，2005，20(2)：78-80．
[56]吴迎春，张尊听，甄宝勤，刘谦光．贯叶连翘化学成分分析．西北农林科技大学学报：自然科学版，2004，32(6)：99-100，106．
[57]吴敏，王霞，许平．贯叶连翘的研究进展．中成药，2004，26(9)：760-763．
[58]孟祥颖，郭良，杨明，李玉新．贯叶连翘挥发油成分的分析．分析化学，2003，31(6)：689-693．
[59]曾虹燕，周朴华．贯叶连翘挥发性成分分析．中药材，2000，23(12)：752-754．
[60]白洁，王冬梅，杨得坡．湖北小连翘中化学成分的高效液相色谱与电喷雾离子化质谱联用分析．武汉植物学研究，2008，26(1)：87-90．
[61]武建芳，路鑫，唐婉莹，孔宏伟，国旺．全二维气相色谱/飞行时间质谱用于连翘挥发油的研究．中国天然药物，2003，1(3)：150-154．
[62]刘力，胡嵘．山羊角研究概述．长春中医学院学报，1994，10(A02)：109-109．
[63]姜清华，翟延君．羚羊角与山羊角药理作用比较．山西医药杂志，2006，35(7)：582-583．
[64]张英杰，苑述刚，阮时宝，洪振丰．熊胆中药学及临床文献研究概述．辽宁中医药大学学报，2010，12(10)：107-108．
[65]罗强，陈全成，吴瑶，姜苗苗，陈志鸿，张晓坤，陈海峰．熊胆的化学成分研究．中国中药杂志，2010(18)：2416-2419．
[66]关晓燕，王熙惠，杨杰．熊胆汁的现状研究．当代医学，2009，15(18)：29-29．
[67]连常宝．熊胆粉的药理作用及临床应用研究概述．海峡药学，2008，20(8)：71-75．
[68]池述广．熊胆主要化学成分合成方法及药理研究进展．海峡药学，2008，20(2)：5-8．
[69]王丽影，高昕，佟子林，王喜军．熊胆的化学成分、药理作用及临床研究概况．中医药信息，2005，22(4)：30-33．
[70] Michael N. Clifford, Susan Knight, Nikolai Kuhnert, Discriminating between the six isomers ofdicaffeoylquinic acid by LC-MSn, Journal of agricultural and food chemistry,2005(53):3821-3832
[71] Wang Zheng, Michael. N. Clifford, Comparison of the profiles of chlorogenic acids and theirderivatives from three Chinese traditional herbs by LC-MSn, Acta Phamaceutica Sinica,2008(43):185-190
[72] Li BQ, Fu T, Dongyan Y, Mikovits JA, Ruscetti FW, Wang JM, Flavonoid baicalin inhibitsHIV-1infection at the level of viral entry, Biochemical and Biophysical ResearchCommunications,2000(276):534-538
[73] Liu IX，Durhan DG, Richards RM, Baicalin Synergy with β-Lactam Antibiotics AgainstMethicillin-resistant Staphylococcus aureus and Other β-Lactam-resistant Strains of S. aureus,Journal of Pharmacy and Pharmacology,2000(52):361-366
[74] Bao Qun Li, Tao Fu, Wang-Hua Gong, Nancy Dunlop, Hsiang-fu Kung, Yaodong Yan, JianKang, Ji Ming Wang, The flavonoid baicalin exhibits anti-inflammatory activity by binding tochemokines, Immunopharmacology,2000(49):295-306
[75] Yonggang Cao, Xiaoyuan Mao, Chunyan Sun, Ping Zheng, Jingquan Gao, Xiaorui Wang,Dongyu Min, Hongli Sun, Ni Xie, Jiqun Ca, Baicalin attenuates global cerebralischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathways, BrainResearch Bulletin,2011(85):396-402
[76] Chun-Ching Lin, Den-En Shieh, In Vivo Hepatoprotective Effect of Baicalein, Baicalin andWogonin from Scutellaria rivularis, Phytotherapy Research,1996(10):651-654
[77] May GR, Sutherland LR, Shaffer EA, Efficacy of bile acid therapy for gallstone dissolution: ameta-analysis of randomized trials, Alimentary Pharmacology&Therapeutics,1993(7):139-148
[78] Karthikesan K, Pari L, Menon VP, Antihyperlipidemic effect of chlorogenic acid andtetrahydrocurcumin in rats subjected to diabetogenic agents, Chemico-Biological Interactions,2010(188):643-650
[79] Hemmerle H, Burger HJ, Below P, Schubert G, Rippel R, Schindler PW, Paulus E, Herling AW,Herling, Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepaticglucose-6-phosphate translocase, Journal of Medicinal Chemistry,1997(40):137-145.
[80] Kwon HakCheol, Jung ChilMann, Shin ChaGyun, Lee JongKyo, Choi SangUn, Kim SunYeou,Lee KangRo, A new caffeoyl quinic acid from Aster scaber and its inhibitory activity againsthuman immunodeficiency virus-1(HIV-1) integrase, Journal Chemical&PharmaceuticalBulletin,2000(48):1796-1798
[81] Mee-Hyang Kweon, Han-Joon Hwang, Ha-Chin Sung, Identification and antioxidant activity ofnovel chlorogenic acid derivatives from bamboo(Phyllostachys edulis), Journal of Agriculturaland Food Chemistry,2001(49):4646-4655
[82] Gui-Feng Wang, Li-Ping Shi, Yu-Dan Ren, Qun-Fang Liu, Hou-Fu Liu, Ru-Jun Zhang, ZhuangLi, Feng-Hua Zhu, Pei-Lan He, Wei Tang, Pei-Zhen Tao, Chuan Li, Wei-Min Zhao, Jian-PingZuo, Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo andin vitro, Antiviral Research,2009(83):186-190
[83]钟敬华，侯晓蓉，范骁辉．化学指纹图谱类别相似性计算方法研究．中国中药杂志，2010，4(35):477-480
[84]詹雪艳，史新元，段天璇，李磊，乔延江．色谱指纹图谱组合相似度的算法．色谱，2010，28(11):1071-1076
[85]孙国祥，侯志飞，张春玲，毕开顺，孙毓庆．色谱指纹图谱定性相似度和定量相似度的比较研究．药学学报，2007，42(1)：75-80
[86] Kuhajda K., Kandrac J., Keresan S., Mikov M, Fawcett J.P., Structure and origin of bile acids:An overview, European Journal Of Drug Methabolism And Pharmacokinetics,2006,31(3):135-143
[87] Natalini, R. Sardella, E. Camaioni, S. Natalini, R. Pellicciari, Dominant Factors Affecting theChromatographic Behaviour of Bile Acids, Chromatographia2006,(64):343–349
[88] Jun Zhang, Min Chen, Wenzheng Ju, Shijia Liu, Meijuan Xu, Jihong Chu, Ting Wu, Liquidchromatograph/tandem mass spectrometry assay for the simultaneous determination ofchlorogenic acid and cinnamic acid in plasma and its application to a pharmacokinetic study,Journal of Pharmaceutical and Biomedical Analysis,2010(51):685–690
[89] T.H. Tsai, Y.F. Chen, A.Y.C. Shum, C.F. Chen, Determination of chlorogenic acid in rat bloodby microdialysis coupled with microbore liquid chromatography and its application topharmacokinetic studies, Journal of Chromatography A,2000(870):443-448
[90] S. J. Choi, C. K. Jeong I, H. M. Lee, K. Kim, K. S. DO, H. S. Lee, Simultaneous Determinationof Ursodeoxycholic Acid and Its Glycine-conjugate in Serum as Phenacyl Esters UsingMultidimensional Liquid Chromatography, Chromatographia1999,50(12):96-100
[91] Jun-Xiao Ye, Wang Wei, Li-Hui Quan, Chun-Yu Liu, Qi Chang, Yong-Hong Liao, AnLC-MS/MS method for the simultaneous determination of chlorogenic acid, forsythiaside A andbaicalin in rat plasma and its application to pharmacokinetic study of Shuang-huang-lian in rats,Journal of Pharmaceutical and Biomedical Analysis,2010(52):625-630
[92] Wei Qi, TingZhao, Wen-WenYang, Guang-HouWang, HuaYu,Hai-Xiao Zhao, ChenYang,Li-XinSun, Comparative pharmacokinetics of chlorogenic acid after oral administration in rats,Journal of Pharmaceutical Ananlysis,2011,1(4):270-274
[93] Rong Gao, Qiang Zheng, Tao Gong, Yao Fu, Li Deng, Zhi-Rong Zhang, Gradienthigh-performance liquid chromatography for the simultaneous determination of chlorogenic acidand baicalin in plasma and its application in the study of pharmacokinetics in rats, Journal ofPharmaceutical and Biomedical Analysis,2007(43):335-340
[94] Tong Lu, Jue Song, Fang Huang, Yuanxiong Deng, Lin Xie, Guangji Wang, Xiaodong Liu,Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radixscutellariae extract and Huang-Lian-Jie-Du-Tang to rats, Journal of Ethnopharmacology,2007(110):412-418
[95] Zi-chuan Zhang, Man Xu, Shi-feng Sun, Xue Qiao, Bao-rong Wang, Jian Han, De-an Guo,Metabolic analysis of four phenolic acids in rat by liquid chromatography-tandem massspectrometry, Journal of Chromatography B,2008(871):7-14
[96] Yuji Matsui, Shun Nakamura, Naoki Kondou, Yoshio Takasu,Ryuji Ochiai, YoshinoriMasukawa, Liquid chromatography-electrospray ionization-tandem mass spectrometry forsimultaneous analysis of chlorogenic acids and their metabolites in human plasma, Journal ofChromatography B,2007(858):96-105
[97] Andreas R., Rechner, Jeremy P.E. Spencer, Gunter Kuhnle, Ulrich Hahn, Catherine A.Rice-Evans, Novel biomarkers of the meatbolism of caffeic acid derivatives in vivo, Free RadicalBiology&Medicine,2001,30(11):1213-1222
[98] M.-P. Gonthier, C. Remesy, A. Scalbert, V. Cheynier, J.-M. Souquet, K. Poutanen, A.-M. Aura,Microbial metabolism of caffeic acid and its esters chlorogenic and caftaric acids by humanfaecal microbiota in vitro, Biomedicine&Pharmacotherapy,2006(60):536-540
[99] Vignot S., Faivre S., Aguirre D. mTOR-targeted therapy of eaneer with rapamycin derivatives.Ann Oncol,2005,16(4):525-537
[100] Jones K., Saadat-Lajevard S., Lee T., et al. An immuno-assay for the lneasurenlent ofsirolinms. Clin Ther,2000,22(suppl B):49-61
[101] Lam M.F., Yip T.P.S., Tse K.C., et al. Sirolimus in kidney transplantation: A pilot study inChinese patients. Hong Kong J Nephrol,2004,6(1):38-42
[102] Campanero M.A., Cardenas E., Sadaba B., et al.Therapeutic drug monitoring for sirolimusin whole blood of organ transplants by high-performance liquid chromatography with ultravioletdetection. J Chromatography A,2004,1031(1-2):265-273
[103] Rangan G.K., Nguyen T., Mainra R., et al. Therapeutic role of sirolimus in non-transplantkidney disease. Pharmacology&Therapeutics,2009,123(2):187-206
[104] Jiao Z, Shi X J, Li Z D, et al. Population pharmacokinetics of sirolimus in de nove Chineseadult renal transplant patients. Br J Clin Pharmacol,2009,68(1):47-60
[105] Macdonald A., Scarola J., Burke J.T., et al. Clinical pharmacokinetics and therapeutic drugmonitoring of sirolimus. Clin Ther,2000,22(suppl B):101-121
[106] Dansirikul C., Morris R.G., Tett S.E., et al. A bayesian approach for populationpharmacokinetic modeling of sirolimus. Br Clin Pharmacol,2006,62(4):420-434
[107]李海宏．痰热清注射液治疗术后并发坠积性肺炎疗效观察．医药产业资讯，2005，2(14)：73
[108] Kim H J, Chang E J, Cho S H, Chung S K, Park H D, Choi S W. Antioxidative activity ofresveratrol and its derivatives isolated from seeds of paeonia lactiflora, Biosci. Biotech. andBiochem.,2002(66):1990-1993
[109] Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., Protein measurement with thefolin phenol reagent, Journal of Biological Chemistry.1951(193):265-275
[110] Bjornsson TD, Callaghan JT, Einolf HJ, et al. Theconduct of in vitro and in vivo drug-druginteraction studies: a Ph RMA perspective, J Clin Pharmcol,2003(43):443-469
[111] Margolis JM, Obach RS. Impact of nonspecific binding to microsomes and phospholip id onthe inhibition of cytochrome P4502D6: imp lications for relating in vitro inhibition data to invivo drug interactions, Drug Metab Dispos,2003(31):606-611
[112] Tran TH, Von Moltke LL, Venkatakrishnan K, et al. Microsomal p rotein concentrationmodifies the apparent inhibitory potency of CYP3A inhibitors, Drug Metab Dispos,2002(30):1441-1445
[113]詹勤．桔梗在升陷汤中引经作用及其化学成分研究．第二军医大学博士论文，2012
[114]邸鹏．丹参酚酸类成分生源途径的探索及相关基因的克隆与功能研究．第二军医大学博士论文，2012
[115]杨琦．知母、黄柏及其药对标准提取物的质量控制研究．第二军医大学硕士论文，2009
[116]位华．五酯胶囊的药代动力学及与他克莫司相互作用研究．第二军医大学博士论文，2010
[117]蔡飞．滋肾丸药代动力学及其配伍机制研究．第二军医大学博士论文，2011
[118]张在丽，郭燕萍，李中东，施孝金，钟明康．西罗莫司胶囊在人体内的生物等效性评价．中国药学杂志，2012
[119]姜波．常用中成药对细胞色素P4503A4和P-糖蛋白的诱导研究．第二军医大学硕士论文，2010
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[24]刘冠军，王合群，殷海燕．痰热清注射液治疗肾病综合征出血热发热期患者46例临床观察．中原医刊，2005，32(13)：46-47．
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[27]王江桥．痰热清注射液治疗急性脑卒中继发肺部感染18例临床观察．中原医刊，2005，32(1)：40
[28]陈玉清，李琳，张茵等．痰热清注射液治疗传染性单核细胞增多症24例．中医研究，2005，18(7)：45-46．
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[30]刘红敏，乔秋杰，曹亚飞．中药痰热清注射液治疗急性风湿热疗效观察．中医正骨，2005，17(6)：16-17．
[31]许晓菲，痰热清注射液致不良反应文献分析．中国医药指南，2012，10（15）：409-411
[32]谢本树，张海英．痰热清致过敏性休克1例．中国药学杂志，2010，45(12)：918-919．
[33]张晋萍，冯宁宁．痰热清注射液致视物模糊1例．医药导报，2009，28(7)：915-916．
[34]张龙英．痰热清注射液致过敏性休克1例．医疗装备，2011，25(11)：51．
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[40]李洪杰，张剑，程连房．痰热清注射液致过敏性休克1例．内蒙古中医药，2011，30(22)：34．
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[42]薛东升，李小利，宋庆宏．痰热清注射液作用机理与临床应用．上海医药，2007
[43]李富善，黄晓玲．痰热清注射液的作用机理和临床应用．青海医药杂志，2011
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