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Journal of Ocean University of China 2022年第3期21卷 782-788页

作者： ZHANG Pengpeng ZHANG Miaomiao DONG Kaiyu ZHANG Yicong YANG Shuang WANG Yuanhong JIANG Tingfu YU Mingming LV Zhihua School of Medicine and Pharmacy Ocean University of ChinaQingdao266003China laboratory for Marine Drugs and Bioproducts of Qingdao National laboratory for Marine Science and Technology Qingdao266003China Key laboratory of Glycoscience&Glycotechnology of Shandong Province Qingdao266003China Key laboratory of Marine Drugs Ministry of Education of ChinaQingdao266003China

Chito-oligosaccharide(COS)had shown a variety of biological activities and potential biomedical *** present study investigated the pharmacokinetics,bioavailability,and in vitro absorption of COS with degrees of polymerization(DPs)2-7 and explored the influence of DPs on *** Caco-2 cell permeation studies,COS were low permeability compounds with no directional effects,suggesting a low in vivo absorption mediated by facilitation diffusion and paracellular *** an intragastrical administration to rats,COS2 showed the highest systemic exposure in six *** bioavailability of COS2-7 was 7.33%,6.11%,4.67%,4.13%,4.02%,0.99%,*** in bioavailability for each COS correlated to structural variations,with high DPs contributing to a decrease in *** conclusion,COS could be absorbed by the intestinal tract both in vitro and in *** very low oral bioavailability of COS could be due to low *** can affect absorption and bioavailability of *** study provided evidence for the absorption characteristics of COS2-7 to help us better understanding the pharmacological actions.

关键词： chito-oligosaccharide(COS) Caco-2 transport pharmacokinetics bioavailability

Development and Application of Network Toxicology in Safety Research of Chinese Materia Medica

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Chinese Herbal Medicines 2015年第1期7卷 27-38页

作者： Xing Zhang Hui-rong Fan Ya-zhuo Li Xue-feng Xiao Rui Liu Jing-wen Qi Jie Wang Zong-peng Zhang Chang-xiao Liu Xiu-ping Shen Research Center for Drug Evaluation State Key Laboratory of Drug Delivery Technology and Pharmacokinetics Tianjin Institute of Pharmaceutical Research School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine Drug Informatics Center Tianjin Institute of Pharmaceutical Research

Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica （CMM）. The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.

关键词： Chinese materia medica drug safety network biology network pharmacology networktoxicology toxicology database traditional Chinese medicine

Key Techniques and Application Progress of Molecular Pharmacognosy

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Chinese Herbal Medicines 2011年第2期3卷 106-116页

作者： XIAO Xue-feng1,HU Jing1,XU Hai-yu2,5,GAO Wen-yuan3,ZHANG Tie-jun4,LIU Chang-xiao2 1.School of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China 2.The National Key laboratory of pharmacokinetics and Pharmacodynamics,Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China 3.School of Pharmaceutical Science and Technology,Tianjin University,Tianjin 300072,China 4.Research Center of Modern Chinese Medicines,Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China 5.Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine Tianjin 300193 China The National Key laboratory of pharmacokinetics and Pharmacodynamics Tianjin Institute of Pharmaceutical Research Tianjin 300193 China Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing 100700 China School of Pharmaceutical Science and Technology Tianjin University Tianjin 300072 China Research Center of Modern Chinese Medicines Tianjin Institute of Pharmaceutical Research Tianjin 300193 China The National Key laboratory of pharmacokinetics and Pharmacodynamics Tianjin Institute of Pharmaceutical Research Tianjin 300193 China

At the boundary between pharmacognosy and molecular biology,molecular pharmacognosy has developed as a new borderline *** paper reviews the methods,application,and prospect of molecular *** marker is one of genetic markers and some molecular marker methods which have been successfully used for genetic diversity identification and new medicinal resources *** DNA technology provides a powerful tool that enables scientists to engineer DNA *** chip technique could be used in determination of gene expression profiles,analyses of polymorphisms,construction of genomic library,analysis of mapping,and sequencing by *** the methods and theory of molecular biology and pharmacognosy,molecular pharmacognosy represents an extremely prospective branch of pharmacognosy and focuses on the study of systemic growth of medicinal plants,identification and evaluation of germplasm resources,plant metabolomics and production of active ***,the great breakthrough of molecular pharmacognosy could be anticipated on DNA fingerprint analysis,cultivar improvement,DNA identification,and a global DNA barcoding system in the future.

关键词： DNA marker genetic diversity molecular biology molecular pharmacognosy pharmacognosy

Separation and determination of acetyl-glutamine enantiomers by HPLC–MS and its application in pharmacokinetic study

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Journal of Pharmaceutical Analysis 2017年第5期7卷 303-308页

作者： Xiaoxiao Zhang Lei Gao Zunjian Zhang Yuan Tian Key laboratory of Drug Quality Control & Pharmacovigilance (China Pharmaceutical University) Ministry of Education State Key laboratory of Natural Medicine China Pharmaceutical University

A high-performance liquid chromatography coupled with mass spectrometry(HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers(acetylL-glutamine and acetylD-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column(250 mm ×4.6 mm, 5 μm). n-Hexane(containing 0.1% acetic acid) and ethanol(75:25, v/v) were used as mobile phase at a flow rate of 0.6 m L/min. The detection was operated in the negative ion mode with an ESI source. [M-H]-m/z187.0540 for enantiomers and [M-H]-m/z 179.0240 for aspirin(IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 μg/m L. The precision of this method at concentrations of 0.5–20 μg/m L was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ(0.05 μg/m L) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers.

关键词： HPLC–MS Acetyl-glutamine Enantiomers separation pharmacokinetics Chiral inversion

Pharmacokinetic profiles of falcarindiol and oplopandiol in rats after oral administration of polyynes extract of Oplopanax elatus

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Chinese Journal of Natural Medicines 2016年第9期14卷 714-720页

作者： SUN Wei HE Yi-Sheng XU Ling-Hui ZHANG Bi-Ying QI Lian-Wen YANG Jie LI Ping WEN Xiao-Dong State Key laboratory of Natural Medicines China Pharmaceutical University

Polyynes, such as facarindiol(FAD) and oplopandiol(OPD), are responsible for anticancer activities of Oplopanax elatus(O. elatus). A novel approach to pharmacokinetics determination of the two natural polyynes in rats was developed and validated using a liquid chromatography-electrospray ionization-mass spectrometry(LC-MS) method. Biosamples were prepared by liquid-liquid extraction using ethyl acetate/n-hexane(V : V = 9 : 1) and the analytes were eluted on an Agilent ZORBAX Eclipse Plus C18 threaded column(4.6 mm × 50 mm, 1.8 μm) with the mobile phase of acetonitrile-0.1% aqueous formic acid at a flow-rate of 0.5 m L·min–1 within a total run time of 11 min. All analytes were simultaneously monitored in a single-quadrupole mass spectrometer in the selected ion monitoring(SIM) mode using electrospray source in positive mode. The method was demonstrated to be rapid, sensitive, and reliable, and it was successfully applied to the pharmacokinetic studies of the two polyynes in rat plasma after oral administration of polyynes extract of O. elatus.

关键词： Oplopanax elatus Polyynes LC-MS Pharmacokinetic study

Ilexgenin A enhances the effects of simvastatin on non-alcoholic fatty liver disease without changes in simvastatin pharmacokinetics

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Chinese Journal of Natural Medicines 2018年第6期16卷 436-445页

作者： LU Ya-Wen ZHU Ying-Chao ZHANG Li LI Ping YANG Jie WEN Xiao-Dong State Key laboratory of Natural Medicines China Pharmaceutical University

Cardiovascular disease(CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease(NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A(IA) is one of the main bioactive compounds in ‘Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin(SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The m RNA levels and activity of CYP3 A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.

关键词： Ilexgenin A Simvastatin Non-alcoholic fatty liver Simvastatin acid pharmacokinetics

Efficacy and safety of novel anticoagulants in the elderly

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Journal of Geriatric Cardiology 2016年第8期13卷 718-723页

作者： Nikolaos Karamichalakis Stamatis Georgopoulos Konstantinos Vlachos Ioarmis Liatakis Michael Efremidis Antonios Sideris Konstantinos P Letsas laboratory of Cardiac Electrophysiology 'Evangelismos' General Hospital of Athens Greece

Atrial fibrillation and venous thromboembolism （VTE） are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of antico-agulants quite challenging. Novel oral anticoagulants （NOACs） have recently emerged as alternatives to Vitamin K Antagonists （VKAs） and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been weU-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population.

关键词： Atrial fibrillation Efficacy Novel oral anticoagulants Safety Venous thromboembolism

多组分中药血塞通注射液在脑缺血患者体内的群体药动学及药效学研究

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中国临床药理学与治疗学 2007年第10期12卷 1183-1184页

作者：李晓宇王广基熊玉卿孙建国郝海平邹浪郑媛婷严蓓夏春华刘皋林 Department of Clinical Pharmacy Affiliated First People Hospital of Shanghai Jiaotong University Key laboratory of Drug Metabolism and pharmacokinetics China Pharmaceutical University Nanjing 210009 Jiangsu China Key laboratory of Drug Metabolism and pharmacokinetics China Pharmaceutical University Institute of Clinical Pharmacology Medical College of Nanchang University Department of Clinical Medicine Jiangxi College of TCM Institute of Clinical Pharmacology Medical College of Nanchang University Nanchang 330006 JiangxiChina

AIM: Pharmacokinetic and pharmacodynamic profiles of Xuesaitong injection in cerebral ischemic patients are investigated in order to optimize dosage regimen of multiple constituent TCM in clinic. METHODS: 63 patients were studied in our protocol. Enumeration and measurement data of all patients were collected during our experiment. Blood samples were collected for two times at different time after intravenous infusion Xuesaitong injection at the dosage of 800 mg/kg for two weeks. Concentration of Xuesaitong injection in plasma, prothrombin time(PT), thrombin time(TT), activated partial thromboplastin time(APTT)and fibrinogen(Fib) were determined. NONMEM and SAAMⅡ were employed for the simulation of PPK parameters and time-course fitting of Xuesaitong injection in cerebral ischemic patients. RESULTS: Population pharmacokinetic (PPK) parameters of Xuesaitong injection obtained as follow: CL1: 1.5 L·h-1·kg-1, CL2: 13.0 L·h-1·kg-1, k10: 0.1136/h, k12: 0.9848/h, k21: 0.2057/h. Inter-individual variability were 36.3%, 17.8%, 1.0% and 60.3%. Residual variability was 8.67%. Age, stature, gender of patients showed no correlation with the prolong ratio of PT(PT%), TT(TT%), APTT(APTT%) and inhibit ratio of Fib(Fib%) whereas dosage (weight), infusion ratio and concentration of Xuesaitong injection in plasma were marked correlation to PT%, TT%, APTT% and Fib%. Correlation coefficient between dosage, infusion ratio, plasma concentration to PT%, TT%, APTT% and Fib% were 0.598, 0.551, 0.590, 0.505; 0.204, 0.401, 0.348, 0.403 and 0.560, 0.436, 0.593, 0.351, respectively. P value was less than 0.01 or 0.05. Best pharmacological effect obtained when Xuesaitong injection was administered as follow: Dosage was of 12.0-17.0 mg/kg, infusion ratio was of 10.0-18.0 mg/min and plasma concentration was of 25.0-35.0 μg/mL. Time course of Xuesaitong injection in cerebral ischemic patients was successfully predicted and simulated results suggested that better effects were obtained at the dosage

关键词：多组分中药血塞通注射液脑缺血群体药动学药效学

LC/MS/MS determination and pharmacokinetic studies of six compounds in rat plasma following oral administration of the single and combined extracts of Eucommia ulmoides and Dipsacus asperoides

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Chinese Journal of Natural Medicines 2014年第6期12卷 469-476页

作者： HUANG Yu-Xing LIU Er-Wei WANG Lei HUO Yan WANG Qiang OLALEYE Olajide WANG Tao GAO Xiu-Mei Tianjin Key laboratory of TCM Chemistry and Analysis Tianjin University of Traditional Chinese Medicine Tianjin State Key laboratory of Modern Chinese Medicine

AIM: To establish and apply a new LC/MS/MS method for the simultaneous, quantitative determination of six ingredients, aucubin(AU), geniposide(GP), geniposidic acid(GPA), pinoresinol diglucoside(PDG), secologanin(SLG), and loganin(LG) in single and combined extracts of Eucommia ulmoides and Dipsacus asperoides. METHOD: Using the LC/MS/MS-ESI--MRM mode to detect the six compounds, chromatographic separation was achieved on an Agilent Eclipse plus C18 column, and the mobile phase consisted of solvent A(CH3CN) and solvent B(H2O containing 0.01% CH3 COOH V/V). RESULTS: This method was successfully applied to quantify the six compounds in rat plasma after oral administration, and showed good precision, accuracy, reproducibility, and linear regression(r2 >0.99). CONCLUSION: The results showed that following the use of the two medicinal plants, for AU and GP, the values of tmax markedly increased, and the values of cmax markedly decreased. It was found that the compatibility of the medicinal plants might affect their pharmacokinetic properties of their constituents.

关键词： pharmacokinetics Compatibility Eucommia ulmoides Dipsacus asperoides LC/MS/MS

Preparation, Characterization and pharmacokinetics of Fluorescence Labeled Propylene Glycol Alginate Sodium Sulfate

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Journal of Ocean University of China 2014年第4期13卷 683-690页

作者： LI Pengli LI Chunxia XUE Yiting ZHANG Yang LIU Hongbing ZHAO Xia YU Guangli GUAN Huashi Key laboratory of Marine Drugs of Ministry of Education Provincial Key Laboratory of Glycoscience and Glycotechnology of Shandong School of Medicine and Pharmacy Ocean University of China

A rapid and sensitive fluorescence labeling method was developed and validated for the microanalysis of a sulfated polysaccharide drug,namely propylene glycol alginate sodium sulfate(PSS), in rat plasma. Fluorescein isothiocyanate(FITC) was selected to label PSS, and 1, 6-diaminohexane was used to link PSS and FITC in order to prepare FITC-labeled PSS(F-PSS) through a reductive amination reaction. F-PSS was identified by UV-Vis, FT-IR and 1H-NMR spectrum. The cell stability and cytotoxicity of F-PSS were tested in Madin-Darby canine kidney(MDCK) cells. The results indicated that the labeling efficiency of F-PSS was 0.522% ± 0.0248% and the absolute bioavailability was 8.39%. F-PSS was stable in MDCK cells without obvious cytotoxicity. The method was sensitive and reliable; it showed a good linearity, precision, recovery and stability. The FITC labeling method can be applied to investigating the absorption and metabolism of PSS and other polysaccharides in biological samples.

关键词： propylene glycol alginate sodium sulfate fluorescence labeling fluorescein isothiocyanate pharmacokinetics