最新刊期
      卷 31 ， 期 7 ， 2020
      • ZHANG Yufei,DONG Chendong,WANG Zizhe,MAO Ningying
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To put forward some suggestions for the implementation of OTC monograph in China. METHODS ： Literature research was used to comprehensively review the concept ，emergence and development ，function of OTC monograph in USA；referring to experience in USA ，the necessity and feasibility of monograph system for OTC registration and evaluation in China were explored ，and some suggestions were put forward to the implementation of OTC monograph in China. RESULTS & CONCLUSIONS：OTC monograph in USA refers to the regulatory standards that should be followed when selling OTC products not included in new drug applications. The monograph originates from the re-evaluation project of the effectiveness of OTC drugs ， which plays a special role in accelerating the drug marketing and promoting product innovation. The OTC monograph system is necessary to help to optimize the OTC registration and evaluation ，but at present ，the conditions to establish and implement OTC monograph are not yet ripe in China. Based on the optimization of resource allocation and infrastructure construction ，national OTC drug management experience ，OTC monograph can play a full part in OTC registration and evaluation ，in terms of carrying out in-depth research ，taking pilot test ，improving risk management system and enhancing drug review resource allocation ability.  
        关键词：OTC drug;Registration and evaluation;Monograph syst em;USA;Enlightenment   
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        发布时间：2022-06-21
      • WANG Qing,ZHANG Rong
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To provide reference for establi shing evidence-based pharmaceutical management and assessment system in China. METHODS ：Through literature study and new medical policy interpretation ，the development course of hospital-based health technology assessment （HB-HTA）and its application in pharmaceutical management at home and abroad were traced；the development prospect of HB-HTA in China ’s hospital drug management was discussed. RESULTS & CONCLUSIONS： The HB-HTA makes scientific evaluation on the process of access and use of medical technology ，so as to optimize the allocation of hospital resources and ensure the quality of medical treatment. Foreign countries have used HB-HTA to assist the decision-making of hospitals. China ’s HB-HTA is still in its initial stage and lags behind the international leading level. As effective means for cost control and quality improvement ，HB-HTA should be applied in drug management and assessment system as soon as possible；it is necessary to explore suitable drug assessment mode （i.g. ambassaclor mode ，Mini-HTA mode ，internal committee mode，HB-HTA unit mode ），strengthen HTA personnel training ，establish HTA methodology （such as Mini-HTA mode assessment tool included outline ，general information ，general methods ，multi-structure evaluation results ，discussion，conclusions and recommendations），pay more attention to it and promote the transformation of achievements.  
        关键词：Hospital-based health technology assessment;Pharmaceutical management;Rational drug use   
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        发布时间：2022-06-21
      • KONG Shujun,CAI Junfei,SUN Xingqian,LIU Yunkuan,MA Yunshu
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To stud y the pharmacok inetics of PELGE-crebanine nanopartic les （PELGE-Cre-NPs） in rabbits. METHODS：Totally 6 rabbits were collected ，and injected with PELGE-Cre-NPs （3.5 mg/kg）via ear vein. 1 mL of blood samples were collected at 5，15，30，60，90，120，150，180，240，300 min after administration from the ear vein. After the plasma were isolated and Cre were extracted with ethyl acetate ，HPLC method was adopted to determine the plasma concentration of Cre by using verapamil hydrochloride as internal standard. The plasma concentration-time curve was drawed and pharmacokinetic parameters were calculated by using DAS 2.0 software. Chromatographic conditions such as the chromatographic column was Agilent ZORBAX Extend-C 18；the mobile phase consisted of methanol- 0.01％ triethylamine solution （75 ∶ 25，V/V）；the flow rate was 1 mL/min；the detection wavelength was 280 nm；the column temperature was 30 ℃；the injection volume was 20 μL. RESULTS：The linear range of Cre were 45.0-3 600 µg/L（R2＝0.999 9）. RSDs of inter-day and intra-day precision and stability tests were all lower than 5％（n＝6 or n＝12）；the accuracies were （97.44±2.41）％-（98.45±3.87）％（n＝6）. PELGE-Cre-NPs was in a two-compartment model in rabbits. Main pharmacokinetic parameters included that t1/2 was（109.357±33.917）min；CL was（0.016±0.001）L/（min·kg）；MRT was （76.733±7.502）min；cmax was（3 699.458±287.713）μg/L. CONCLUSIONS：The half-life period of PELGE-Cre-NPs in rabbits is longer than that of Cre injection；its retention time in the body is prolonged ，and sustained-release effect is obvious.  
        关键词：PELGE-crebanine nanopartic les;Pharmacokinetics;Rabbit;Plasma concentration   
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        发布时间：2022-06-21
      • ZHANG Cong,HU Na,LI Shan,ZHENG Guohua,QIU Zhenpeng
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To study the effects of loganin on the prolife ration and apoptosis of liver cancer HepG 2 cells，and to explore its mechanism. METHODS ：CCK-8 assay was used to detect the effects of different concentrations （10，25，50，100， 150，200，300，400 µg/mL）of loganin on the proliferation activity of HepG 2 cells for 24 and 48 h. HepG 2 cells were divided into control group ，loganin low-concentration ，medium-concentration and high-concentration groups （50，100，150 μ g/mL）. After treated for 24 h，morphological changes of apoptosis of cells were detected by Hoechst 33342 fluorescence staining. The apoptosis and cycle distribution of cells were detected by flow cytometry. Western blotting was used to detect protein expression of Cyclin D1， PCNA， Bcl-2， Caspase-3， Cleaved-Caspase-3， Caspase-9 and Cleaved-Caspase- 9. RESULTS ： Loganin inhibited the proliferation of HepG 2 cells，in concentration-dependent trend. Compared with control group ，apoptosis as pyknosis and fragmentation occurred ，and the apoptosis rate increased significantly in loganin low-concentration ，medium-concentration and high-concentration groups （P＜0.01）；the cell were mainly blocked in S phase ；relative protein expression of Cyclin D 1，PCNA and Caspase- 3 were significantly decreased ，while that of Cleaved-Caspase- 3 were significantly increased in loganin low- concentration， medium-concentration and high-concentration groups （P＜0.05 or P＜0.01）； relative protein expression of Cleaved-Caspase-9 were increased significantly ，while that of Bcl- 2 and Caspase- 9 were decreased significantly in loganin medium-concentration and high-concentration groups （P＜0.05 or P＜0.01）. CONCLUSIONS ：Loganin can significantly inhibit the proliferation and induce apoptosis of HepG 2 cells，the mechanism of which may be associated with inhibiting Bcl- 2 protein expression and promoting Caspase- 3，Caspase-9 activation.  
          
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        发布时间：2022-06-21
      • LAI Gena,JIA Wenyu,LUO Siwan,ZHOU Changyuan,LI Xiong,ZHANG Xian,ZENG Xing
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To establish pre -column derivatization-HPLC fingerprint of Polyporus polysaccharide ，and to determine the contents of main monosaccharide components ，so as to provide reference for quality evaluation of Polyporus umbellatus. METHODS ：Polyporus polysaccharide was extracted with boiling water and precipitated by ethanol and deproteinized by Sevage from 11 batches of P. umbellatus from different producing areas. The samples were firstly hydrolyzed with trifluoro-acetic acid （TFA）and then derivatized by 1-phenyl-3-methyl-5-pyrazolone（PMP）. HPLC analysis was then conducted. The determination was carried out on HypersiL BDS C 18 column with mobile phase composed of 0.1 mol/L phosphate buffer （pH 6.84）-acetonitrile（84∶16，V/V）by gradient elution at the flow rate of 1.0 mL/min. The detection wavelength was set at 254 nm， and column temperature was 30 ℃. The sample size was 20 µL. The similarity of 11 batches of Polyporus polysaccharide was evaluated by using TCM Chromatographic Fingerprint Similarity Evaluation System （2012A edition ），and the contents of main monosassharide components were detected. The peak was identified by comparing with the reference substance ，and cluster analysis was performed by using SPSS 23.0 software. RESULTS ：In HPLC fingerprints of the 11 batches of samples ，3 common peaks were identified ，namely mannose ，glucose and galactose. The similarity of all samples was above 0.94. Cluster analysis classified 11 batches of samples into three categories. S 1-S6，and S 8 were grouped into category 1；S7，S10 and S 11 were grouped into category 2；S9 was individually grouped into one category. Results of content determination showed that the contents of mannose ranged from 1.571 to 8.771 mg/g；those of glucose ranged from 26.072 to 132.194 mg/g，and those of galactose ranged from 3.420 to 36.593 mg/g. CONCLUSIONS ：Established pre-column derivatization HPLC fingerprints can provide reference for quality evaluation of P. umbellatus . The monosaccharide composition of different batches of Polyporus polysaccharide is the same ；there is no significant correlation between fingerprint characteristic peak and the origin of herbs ；there is significant difference in the content of monosaccharide of P. umbellatus .  
        关键词：Polyporus polysaccharide;Monosaccharide;PMP;Pre-column derivatization;HPLC;Fingerprint   
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        发布时间：2022-06-21
      • LU Senhua,GAN Yangying,TANG Lian,ZHANG Fengyi,SU Benwei
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To establish a host specific method for the qual ity evaluation of Taxillus chiueusis by evaluating the quality of T. chiueusis from different hosts sources. METHODS ：HPLC was adopted with CAPCELL PAK C 18 MGⅡ column， mobile phase consisted of methanol- 0.2％ phosphoric acid ，volume flow 1.0 mL/min（gradient elution ），detection wavelength of 254 nm，column temperature of 30 ℃. Totally of 16 batches of T. chiueusis from different hosts sources were collected as sample （4 batches from tea host ，maple host ，willow host and mulberry host respectively ）. HPLC characteristic chromatogram was established with TCM Chromatogram Fingerprint Similarity Evaluation System （2004A edition ），and similarity evaluation was performed. The peak was identified by comparison with the reference substance. IBM SPSS 19.0 software was used for cluster analysis and principal component analysis. RESULTS ：Totally 11 common peaks were demarcated ，peak No. 8，10，11 were identified as rutin ，quercetin and quercitin. The similarity of 16 batches of samples was more than 0.9. The chemical components of T. chiueusis from different hosts sources were basically the same （RSDs of relative time of commom peaks were 0.03％-0.40％）， but the contents of the same component were quite different （RSDs of relative peak area of commom peaks were 27.00％-64.20％）. By cluster analysis ，16 batches of T. chiueusis from different hosts sources were divided into 3 types. The results of principle component analysis showed that quercetin ，quercitin and rutin had significant effect on the quality of T. chiueusis ，which could be used as the quality evaluation index ，and the whole quality of maple host was the best （the highest comprehensive score ）. CONCLUSIONS： HPLC fingerprint combined with chemometrics can be used to evaluate the quality of T. chiueusis from different hosts sources.  
          
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        发布时间：2022-06-21
      • ZHU Yanan,ZHANG Shuo,ZHANG Min,MENG Xiaoxia,YANG Qimei,TANG Lei,ZHANG Rongping,GAO Xiuli
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To isolate and purify baicalin metabolites from rat bile ，and to study its effect on the proliferation of liver cancer HepG 2 cells. METHODS ：Totally of 6 SD rats were collected ，anesthetized and then intubated with bile ducts. They were given baicalin （168 mg/kg）intragastrically after the rats were awake as well as the bile sample 1 was collected during 24 h after intragastric administration. After processed ，bile sample 1 was preliminarily analyzed by HPLC. Another 5 SD rats were anesthetized and intubated in the same way as above ，and then given baicalin intragastrically （400 mg/kg）. The bile sample 2 was collected during 48 h after intragastric administration. After processed ，the bile sample 2 was isolated and purified by semi-preparative HPLC. The isolated metabolites were identified by using UV ，IR，MS and NMR ，as well as based on physical and chemical properties. MTT method combined with high content cell imaging analysis system was used to study the effect of the metabolites on the proliferation of HepG 2 cells. RESULTS ：Baicalin was mainly metabolized into metabolite 1 and metabolite 2 through bile. After isolation and purification ， they were identified as oroxylin A- 7-O-β-D-glucuronide and 2726719792@qq.com baicalein 6-O-β-D-glucuronide. The results of MTT assay showed that the metabolite 2 had a significant inhibitory effect 分析。E-mail：gaoxl@gmc.edu.cn on the proliferation of HepG 2 cells，and its IC 50 was 90 µg/mL；the results of high content cell imaging analysis showed that at a certain concentration metabolite 2 may inhibit proliferation by changing the mitochondrial distribution and membrane permeability of HepG 2 cells（studies on the pharmacological activities of metabolism 1 had been reported ，it was skipped in this study ）. CONCLUSIONS ：In this study ，two baicalin bile metabolites were successfully isolated and identified ，of which baicalein 6-O-β-D-glucuronide has a significant inhibitory effect on the proliferation of HepG 2 cells.  
          
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        发布时间：2022-06-21
      • YAN Hua,WEI Feng,MA Shuangcheng
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To compare the quality between Stamen typhae and pollen of T. angustifolia ，and provide scientific evidence for the improvement of quality standard of T. angustifolia . METHODS ：Fifteen batches of S. typhae were collected. Pollen minus sieve ，impurity plus sieve （filament and anther ）were sift out from S. typhae according to the identification method of T. angustifolia in Chinese Pharmacopoeia （2015 edition）. The characteristics and components of S. typhae and pollen ，filament and anther of T. angustifolia were comfirmed by impurity ， character examination and microscope ， TLC. The contents of isorhamnetin-3-O-neohesperidoside and typhaneoside in S. typhae and pollen ，impurities plus sieve （filament and anther ）of T. angustifolia were determined by HPLC. RESULTS ：S. typhae was a mixture of pollen ，anther and filament of T. angustifolia ，in the form of brownish yellow flocculent. The pollen of S. typhae was yellow powder with delicate hand feel ，slight smell and light taste；the surface of cells was slightly striped. The filaments and anthers were filiform and short-term ，rough and astringent ，and the cell surface were long strip. TLC chromatogram of S. typhae ，pollen and impurity of T. angustifolia had the same color spots at the same location. The contents of isorhamnetin- 3-O-neohesperidoside，typhaneoside and their aggregate were the highest in pollen （0.42％，0.24％，0.64％）；the second in S. typhae （0.22％，0.17％，0.39％）；the lowest in the impurities plus sieve （0.19％， 0.14％，0.33％）. The total contents of isorhamnetin- 3-O-neohesperidoside and typhaneoside in S. typhae and in impurities plus sieve did not reach the content limit stipulated in Chinese Pharmacopoeia （not less than 0.50％）. CONCLUSIONS：The medicinal components of T. angustifolia mainly exist in pollen. It is suggested that S. typhae should be used as the raw material to obtain pollen，and should not be used directly.  
        关键词：Typha angustifolia;Stamen typhae;Medicinal part;Isorhamnetin-3-O-neohesperidoside;Typhaneoside;Quality   
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        发布时间：2022-06-21
      • DU Mengjiao,CHEN Jianping,YU Jiaxian,MEI Wenjie,YU Chuqin,WANG Yandong
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To study the protective effect of timosaponin BⅡ（TB-Ⅱ）on blood vessels and explore its possible mechanism. METHODS ：Using aquaculture water as blank control ，the effects of 100，200 and 400 μg/mL TB-Ⅱ treatment for 48 h on the situation of subintestinal veins （SIVs）in normal zebrafish embryos 24 h after fertilization （24 hpf）were investigated. PTK787（0.06 μg/mL），a tyrosine kinase inhibitor ，was used to induce the model of zebrafish intestinal vascular injury ；using combing with 0.1％ dimethyl sulfoxide but no PTK 787 as blank control ，combing with PTK 787 but no drug as model control ，the effects treatment of 100，200 and 400 μg/mL TB-Ⅱ for 48 h on the SIVs of zebrafish model with vascular injury were investigated. Relative expressions of fam-like tyrosine kinase 1（Flt-1），kinase insert domain containing receptor （Kdr），kinase insert domain containing receptor l （Kdr-l），vascular endothelial growth factor A （VEGF-A），tumor necrosis factor α（TNF-α）and interleukin 6 （IL-6）mRNA were detected by RT-PCR. RESULTS ：100 μg/mL TB-Ⅱ could significantly increase the sprouting vessel of normal zebrafish SIVs sprouting vessel number （P＜0.05），and 200 μg/mL TB-Ⅱ could significantly increase SIVs number of normal zebrafish （P＜0.05）. Compared with blank control ， SIVs treatment （P＜0.01），and the relative expressions of Flt-l ， Kdr，Kdr-l，VEGF-A，TNF-α and IL-6 mRNA were alse decreased significantly （P＜0.05 or P＜0.01）. After treated 化。E-mail：pn333@163.com with different concentrations of TB- Ⅱ ，SIVs number of vascular injury model zebrafish increase d to different extents ；relative expressions of Flt-l ，Kdr，Kdr-l，VEGF-A，TNF-α and IL-6 mRNA were increased to different extents. There was no significant difference in SIVs number and the expression of Flt-l ，TNF-α mRNA in zebrafish treated with 100 μg/mL TB-Ⅱ and the expression of TNF-α mRNA in zebrafish treated with 400 μg/mL TB-Ⅱ， but there was statistical significance in other indexes （P＜0.05 or P＜0.01）. CONCLUSIONS ：TB-Ⅱ has a certain function of promoting angiogenesis and repairing damaged blood vessels ，and its mechanism is related to the up-regulation of vascular endothelial growth factor receptor and pro-inflammatory cytokine expression.  
        关键词：Timosaponin B Ⅱ;Vascular protection;Zebrafish;Subintestinal veins;Mechanism   
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        发布时间：2022-06-21
      • FU Bingyue,ZHANG Ning,ZHANG Zonglei,DUAN Chonggang
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To optimize the synthesis process of dapoxetine hydrochloride. METHODS ：By chiral synthesis ， asymmetric reduction was carried out by using 3-chlorophenylacetone as raw material ，（1S，2R）-（-）-1-amino-2-indanol as catalyst，and borane- N，N-diethylaniline （DEANB） as reducing agent. Then ，it was reacted with α-naphthol etherification， sulfonation，dimethylamine substitution ，and HCl salt formation reaction to obtain the final products. The products were characterized by NMR and MS. The synthesis reaction of intermediate Ⅰ，intermediate Ⅱ，intermediate Ⅲ and the final product were optimized. RESULTS ：The final product was dapoxetine hydrochloride with purity of 99.8％ and yield of 58.9％. Compared with traditional splitting technology ，the chiral synthesis technology of this study did not need splitting ，and the yield of the technology was significantly higher than that of splitting technology reported in literature （31.9％）. The optimized technology reduced the generation of impurities and improved the product quality. CONCLUSIONS ：The improved technology has milder reaction conditions ，shorter synthesis route and higher yield.  
        关键词：Dapoxetine hydrochloride;Chiral synthesis;Asymmetric reduction;Technology optimization   
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        发布时间：2022-06-21
      • XIE Mingyan,ZHANG Zheng,HUANG Yao,ZHANG Zhipeng,HU Yao,CHENG Xueren
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To establish HP LC ch aracteristic ch romatogram of different medicinal parts of Cirsium japonicum ， and to compare the difference of chemical components in different medicinal parts of C. japonicum according to chemical identification method ，and to provide reference for quality control and evaluation of C. japonicum . METHODS ：Medicinal material （overground part ），leaves，flower，main stem and lateral stem of C. japonicum were determined by HPLC. According to the TCM Chromatographic Fingerprint Similarity Evaluation System （2012A edition ），the chromatograms were matched to generate the HPLC characteristic chromatogram of each medicinal part. The differences of common characteristic peak area were analyzed according to variance analysis of single factor. The chromatographic peaks were identified by comparison of reference substance. Meanwhile，the chemical pattern recognition was performed to research the different medicinal parts of C. japonicum according to principal component analysis （PCA）and cluster analysis. RESULTS ：HPLC characteristic chromatograms of medicinal material ， leaves，flower，main stem and lateral stem from C. japonicum were established respectively ，and 15 common peaks were confirmed for medicinal material ，leaves and flower of C. japonicum ；11 common peaks were confirmed in chromatograms of main stem and lateral stem from C. japonicum （absence of No. 7，9，12，13 peak）. The contents of chemical components were different greatly among different medicinal parts. No. 1，2，3，10，11 peaks were identified as neochlorogenic acid ，chlorogenic acid ， cryptochlorogenic acid ，linarin and pectolinarin. Results of PCA and cluster analysis showed that chemical pattern recognition and clustering of the flower and stem of C. japonicum were distinct and can be clustered into one category respectively. However ，the leaves distribution of C. japonicum was relatively scattered ，so it was difficult to cluster . CONCLUSIONS ：Established HPLC characteristic chromatogram-chemical pattern recognition can reflect the differences of different medicinal parts of C. japonicum integrally， comprehensively and truly ， which has vital significance for origin indentification ， quality control and overall evaluation of C. japonicum .  
          
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        发布时间：2022-06-21
      • LI Haoxian,LIN Huaqing,LI Junjian,WANG Yuanjian,LIU Rong,YU Chuqin
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE： To establish the method for simultaneous determination of four known related substances （olmesartan，olmesartan ester dimer ，olmesartan ester alkene ，benzothiadiazine impurity ，called impurity A ，B，C，D for short ）in Olmesartan medoxomil hydrochlorothiazide tablets. METHODS ：HPLC-principal component self-control with correction factor were adopted. The determination was performed on YMC-Triart C 8 column with mobile phase A consisted of acetonitrile- 0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（70 ∶ 30，V/V），mobile phase B consisted of acetonitrile-0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（15 ∶ 85，V/V）at the flow rate of 0.8 mL/min（gradient elution ）. The detection wavelength was set at 265 nm，and column temperature was 25 ℃. The temperature of injector was 4 ℃；the injection volume was 10 μL. RESULTS：The correction factors of impurity A ，B，C，D were 1.42，1.17，0.89，0.92，respectively. The linear range of olmesartan medoxomil ，hydrochlorothiazide and impurity A ，B，C，D were 0.252 7-7.580 0，1.152 1-4.562 9，0.244 0-18.299 0，0.244 7-3.670 8，0.265 2-3.978 3 and 0.149 9-4.497 3 μg/mL（r≥ 0.999 7），respectively. The limits of detection were 0.084 2，0.050 7，0.081 3，0.081 6，0.088 4，0.050 0 μg/mL，respectively. The quantitative limits were 0.252 7，0.152 1，0.244 0，0.244 7，0.265 2 and 0.149 9 μg/mL，respectively. The results of intermediate precision ，stability（24 h）and repeatability tests all met the relevant requirements. The average recovery rates were 104.00％-108.04％，102.00％-104.94％，100.99％-106.89％，92.00％-95.18％，102.00％-105.06％，103.90％-107.00％（n＝3）， respectively. The contents of impurity A ，B and D in 3 batches of Olmesartan medoxomil hydrochlorothiazide tablets were 0.90％ -1.00％ ，0-0.11％ ，0.16％ -0.24％ ，respectively. The impurity C and other impurities were not detected. There is no significant difference between the results measured by the established method and by the external standard method. CONCLUSIONS：The method has been proved to be highly sensitive and reproducible. It can be used to simultaneously determine four known substances in Olmesartan medoxomil hydrochlorothiazide tablets.  
        关键词：Olmesartan medoxomil hydrochlorothiazide tablets;Related substances;HPLC;Principal component self-control   
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        发布时间：2022-06-21
      • ZHAO Yuhong,SHEN Hua,DAI Shuangyi,PU Zhonghui,XIE Zirui,XIAO Ling,KUANG Min,DAI Min
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To establish a method for the content determination of to tal flavonoids from Amomum tsao-ko ，and to optimize the purification technology by macroporous resin. METHODS ：The content of total flavonoids was measured by HPLC. The determination was performed on Eclipse Plus C 18 column with mobile phase consisted of acetonitrile- 1％ acetic acid solution （15∶85，V/V）at the flow rate of 0.8 mL/min. The column temperature was 40 ℃，and the detection wavelength was set at 256 nm. The sample size was 10 μL. Taking the adsorption and desorption performance as indexes，6 kinds of macroporous resins were screened out by static adsorption and desorption tests ；adsorption and desorption time were investigated by static adsorption and desorption kinetics tests. Using the content of total flavonoids （calculated by rutin ）as index ，with sample concentration ，sample pH，ethanol volume fraction and elution amount as factors ，based on single factor test ，orthogonal design was used to optimize the purification technology of total flavonoids from A. tsao-ko ，and validation test was performed. RESULTS ：The linear range of rutin were 0.028-0.281 mg/mL（r＝0.999 9）. The limit of quantification was 437.5 ng/mL and the limit of detection was 109.4 ng/mL. RSDs of precision ，stability and reproducibility tests were all lower than 2％；the recoveries were 96.24％-99.75％（RSD＜2％，n＝ 6）. The comprehensive capacity of adsorption and desorption of HPD 450 macroporous resin was the most suitable ，and the best static adsorption and desorption time both were 12 h. The optimal purification technology was 1.854 4 mg/mL ； ethanol elution was 8 times of the column volume. Vertificationtests show that after optimized ，the content of total flavonoids from A. tsao-ko increased from 22.556 7 mg/g to 57.728 2 mg/g. The purity of was 2.56 and stable for the content determination. Optimal purification technology is stable and feasible ，which is suitable for purifieation of total flavonoids from A. tsao-ko .  
        关键词：Amomum tsao-ko;Total flavonoids;Content determination;Macroporous absorption resin;Purification technology   
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        发布时间：2022-06-21
      • LIU Guoqiang,KANG Shuo
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To evaluate the drug economy of ixekizumab in the treatment of moderate-to-severe plaque psoriasis. METHODS： Literatures were retrieved from PubMed ， Embase， The Cochrane Library ， CNKI and Wanfang database ， supplemented by manual search ，search time from the database establishment to Oct. 31st，2019，using Chinese and English search terms included “Ixekizumab”“Taltz”“Psoriasis”“Pharmacoeconomics”“Cost-benifit analysis ”“Cost-effectiveness analysis ” “Cost-utility analysis ”，etc. The literatures were screened according to inclusion and exclusion criteria. Relevant pharmacoeconomic studies about ixekizumab in the treatment of moderate-to-severe plaque psoriasis were collected ，and the study methods and pharmacoeconomic evaluation results were summarized. RESULTS ：A total of 8 literatures were included ，involving 9 studies. The overall quality of the studies was high. All the studies were distributed in foreign countries such as Canada ，the United States and the United Kingdom. All the studies adopted Markov model. The health outcomes showed that ixekizumab could bring more quality-adjusted life years. Compared with methotrexate combined with phototherapy ，infliximab，ustekinumab and secukinumab ， the incremental cost-utility ratio （ICUR）of ixekizumab was different in different studies. CONCLUSIONS ：Ixekizumab has certain economic advantages for the treatment of moderate-to-severe plaque psoriasis ，but there is still a lack of relevant research in China and it is urgent to carry out relevant research suitable for Chinese.  
        关键词：Ixekizumab;Moderate-to-severe plaque psoriasis;Pharmacoeconomics;Cost-utility analysis   
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      • ZHENG Chunxia,ZHENG Xiaoying,KONG Lingxi,QIU Feng,SHAN Xuefeng
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To study the potential ris k of Chinese patent medicine for the treatment of stable chronic obstructive pulmonary disease （COPD），and to provide reference for the safety of clinical drug use. METHODS ：Retrieved from Chinese journal full-text database ，CBM，Wanfang database and VIP ，using“stable”“Chronic obstructive pulmonary disease ”“COPD” “Chinese patent medicine ”as retrieval words ，relative literatures about Chinese patent medicine in the treatment of stable COPD were retrieved ，and retrieval time limitation was from their establishment to Sept. 2019. The type and components of Chinese patent medicine were collected. The potential risk of Chinese patent medicine was analyzed in terms of the contraindications of traditional Chinese medicines ，the interaction between traditional Chinese medicines and chemical medicines ，and its effects on stable COPD with other common chronic diseases. RESULTS ：Eleven related studies covering 29 kinds of Chinese patent medicines for the treatment of stable COPD were included in this study. There were several incompatibility between two Chinese patent medicines containing Aconitum carmichaelii and eleven Chinese patent medicines containing “Pinellia ternata ，Trichosanthes kirilowii ， Bolbostemma paniculatum ，Ampelopsis japonica ，Bletilla striata ”as an ancient rule of traditional Chinese medicine incompatibility “Eighteen antagonisms ”and“Nineteen mutual ”inhibitors. Meanwhile ，it should be avoided that four Chinese patent medicines containing ephedra combined with β2 receptor agonists or theophylline. Moreover ，oral antibiotics and 14 kinds of Chinese patent medicine containing licorice would reduce the curative effect. In addition ，patients with stable COPD who also had hypertension ， hyperlipidemia or diabetes should be careful to use Chinese patent medicines containing ingredients such as Glycyrrhiza uralensis ， A. carmichaelii ，Ephedra sinica ，Citrus aurantium ，Cornus officinalis ，Fritillaria cirrhosa ，Panax ginseng （Panax notoginseng ）. CONCLUSIONS：There are many potential risks （such as combined use ，compatibility）in the use of Chinese patent medicines for stable COPD. It is suggested to comprehensively evaluate the patient ’s previous medical history and medication before using Chinese patent medicines ，so as to provide scientific guide for clinical rational medication.  
          
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      • LIU Zheng
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To study the effects of montelu kast sodium in the treatme nt of pertussis in children. METHODS ：A total of 160 children aged 6 months-6 years with pertussis admitted to our hospital from Jan. 2017 to Jul. 2018 were randomly divided into control group and observation group ，with 80 cases in each group. Control group received routine treatment such as antibiotics. Observation group was additionally given Montelukast sodium granule or chewable tablets orally （granule for age below 2 years old ，taking with warm water ；chewable tablets for age more than 2 years old ），4 mg/d，once a night. Treatment course of 2 groups lasted for 2 weeks. The changes of clinical indexes as clinical symptoms ，clinical efficacy ，the occurrence of ADR ，and lab indexes as lung function [VPEF/VE，TPTEF/TE，FEV1，FVC，FEV1/FVC]，T lymphocyte subsets （CD4+，CD8+ and CD 4+/CD8+） level，immunoglobulin（IgE，IgG，IgA）level，serum leukotriene （LTB4，LTC4，LTD4）level were compared between 2 groups. RESULTS：Compared with control group （80.00％），total effective rate rate of observation group （95.00％）was significantly increased（P＜0.05）；the cough time of spasm ，the echo time of cockcrow ，the blue and purple time of face caused by cough ，the time of vomit caused by cough ，the time of lung rale and the time of hospitalization were significantly shorter （P＜0.05）；new respiratory tract infection incidence of observation group was lower than that of control group （P＜0.05）；but there was no significant difference in the incidence of ADR between 2 groups after treatment （P＞0.05）. The levels of VPEF/VE ，TPTEF/TE or FEV1，FVC，FEV1/FVC，the levels of peripheral CD 4+ and CD 4+/CD8+，serum levels of IgG and IgA in observation group were significantly increased ，compared with control group ；the level of peripheral CD 8+ and the serum levels of IgE ，LTB4，LTC4 and LTD4 were significantly decreased ，compared with control group （P＜0.05）. CONCLUSIONS ：The addition of montelukast sodium to the routine treatment of pertussis can improve clinical symptoms and lung function of children ，regulate immune function of children and inhibit the release of airway leukotrienes ，which has certain clinical application value.  
          
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      • LIU Shuang,SONG Zaiwei,YI Zhanmiao,ZHAO Rongsheng
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To systematically evaluate the c orrelation of methylenetetra hydrofolate reductase （MTHFR）C677T and A 1298C gene polymorphisms with blood system adverse events induced by high-dose of methotrexate （HDMTX）. METHODS ： Retrieved from Medline ，Embase，Clinical Trials.gov ，CNKI，Wanfang database ，CBM，cohort studies about MTHFR gene polymorphism in hematological neoplasm treated by HDMTX were collected from inceptions to March 2018. After data extraction of included literatures ，quality evaluation with Newcastle Ottawa scale ，Meta-analysis was performed for adverse events of blood system induced by HDMTX in different genetic models with Rev Man 5.3 software. RESULTS ：Totally 25 cohort studies were included，23 studies of which were related to MTHFR C677T site （including 1 858 patients）and 16 studies related to MTHFR A1298C site （including 1 088 patients）. Results of Meta-analysis showed that MTHFR C677T mutation type significantly increased the risk of hematotoxicity [TT/CT vs. CC ：OR＝1.57，95％CI（1.12，2.20），P＝0.009；TT vs. CT/CC ：OR＝2.19，95％CI（1.49， 3.23），P＜0.001；T vs. C ：OR＝1.34，95％CI（1.03，1.74）， P＝0.03] and severe hematotoxicity [TT/CT vs. CC ：OR＝m 2.33，95％CI（1.43，3.81），P＜0.001]，including leukopenia [TT/CT vs. CC ：OR＝1.37，95％CI（1.02，1.82），P＝0.03]， severe leukopenia [TT/CT vs. CC ：OR＝1.63，95％CI（1.03， 010-82265810。E-mail：zhao_rongsheng@163.com 2.56），P＝0.04]，severe gra nulopenia [TT/CT vs. CC ：OR＝ ·2.26，95％CI（1.50，3.39），P＜0.001]. The mutation genotypes of MTHFR A1298C significantly decreased the risk of severe hematotoxicity [CC/AC vs. AA ：OR＝0.17，95％CI（0.04，0.76），P＝0.02]，including leukopenia [CC/AC vs. AA ：OR＝0.68， 95％CI（0.48，0.97），P＝0.03；CC vs. AC/AA ：OR＝0.28，95％CI（0.14，0.59），P＜0.001] and severe leukopenia [CC/AC vs. AA：OR＝0.43，95％CI（0.19，0.97），P＝0.04]. CONCLUSIONS ：Among patients with hematological neoplasms ，MTHFR C677T mutation may significantly increase the risk of hematotoxicity by HDMTX including the risk of leukopenia and granulopenia ；while MTHFR A1298C may reduce the risk of hematotoxicity by HDMTX ，including the risk of leukopenia.  
          
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      • LIU Xin,XU Changjing,ZHONG Xiaoyan,ZHAO Danjie,YU Bin,HUANG Yilan
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To systematically evaluate the efficacy and safety of pe ficitinib for treating rheumatoid arthritis （RA），and to provide evidence-based reference for the clinical treatment of RA. METHODS ：Retrieved from PubMed ，Embase， The Cochrane Library ，CJFD，VIP and Wanfang database during from their establishment to September 2019，randomized controlled trials （RCTs）about the efficacy and safety of Peficitinib （trial group ）versus placebo （control group ）in the treatment of RA were collected. The risk of bias assessment tool provided in Cochrane System Evaluator Manual 5.1.0 was used to evaluate the quality after data extracted from clinical studies which met the inclusion criteria. Meta-analysis of the efficacy [the proportion of patients who met the American College of Rheumatology 20％ improvement criteria （ACR20），ACR50，ACR70，the proportion of the patients with 28 joint disease activity index ＜2.6 calculated by erythrocyte sedimentation rate （DAS28-ESR＜2.6），the proportion of patients with 28 joint disease activity index ＜2.6 calculated by C-reactive protein （DAS28-CRP＜2.6），etc.] and safety（incidence of total ADR ）was performed by using Stata 16 statistical software. RESULTS ：Totally 5 RCTs were included ， 药学。E-mail：hyl3160131@163.com 5.11），P＜0.001]，150 mg[RR＝3.52，95％CI（1.78，6.96），P＜ 0.001]}，ACR70{total [RR ＝2.51，95％CI（1.52，4.14），P＜0.001]，100 mg[RR＝3.50，95％CI（1.62，7.58），P＝0.001]，150 mg [RR＝4.59，95％CI（1.47，14.30），P＝0.009]}，DAS28-ESR＜2.6{total [RR ＝4.83，95％CI（3.20，7.28），P＜0.001]，100 mg[RR＝ 5.37，95％CI（2.68，10.77），P＜0.001]，150 mg[RR＝7.44，95％CI（3.78，14.65），P＜0.001]} and DAS 28-CRP＜2.6{total [RR ＝3.41， 95％CI（2.65，4.39），P＜0.001]，100 mg[RR＝4.00，95％CI（2.67，5.99），P＜0.001]，150 mg[RR＝4.45，95％CI（2.99，6.63），P＜ 0.001]} in trial group were significantly higher than control group ，with statistical significance. In term of safety ，there was no statistical significance in the incidence of total ADR [RR ＝1.05，95％ CI（0.94，1.16），P＝0.395] between 2 groups. CONCLUSIONS：For the treatment of RA ，100 mg or 150 mg peficitinib once per day is superior to placebo in terms of ACR 20， ACR50 and ACR 70，DAS28-ESR＜2.6，DAS28-CRP＜2.6； the adverse events are mild and tolerable and it may be a new treatment option for RA.  
        关键词：Peficitinib;Rheumatoid arthritis;JAK inhibitor;Meta-analysis   
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      • QIAO Lijuan,CHU Yaojuan,ZHANG Rui,QIAO Gaoxing,YIN Zhao,SHI Xiangfen,YU Pei,DU Shuzhang
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To establis h the evaluation model of hospital pharmacist post value of dispensing department ，and to provide scientific basis for optimizing the performance management of pharmacists in despensing department in hospital. METHODS：Based on factor counting method ，combined with questionnaire ，Delphi expert correspondence method and so on ，the hospital pharmacist post value evaluation model was established. Based on this ，the relative value scores of the pharmacists in the dispensing department was determined. RESULTS ：Hospital pharmacist post value evaluation model was established with 5 evaluation dimensions （knowledge，skills，responsibility，work autonomy ，work environment and intensity ，of which the first level weight coefficients were 0.194，0.166，0.365，0.216 and 0.058，respectively）and 31 evaluation elements. The above 5 evaluation dimensions contained 5，8，9，3，6 evaluation elements ，respectively，and the corresponding second-level weights were 0.052-0.431 （for example ，responsibility dimension with the highest weight ，including quality and safety control ，decision responsibility，responsibility for finance and assets ，the corresponding second-level weight coefficients were 0.279，0.140，0.132， respectively）. The relative value scores of 13 pharmacist post were 342.9-840.4 in the dispensing department of our hospital with this model ，among which the department responsible person had the highest score （840.4）and the prescription post score was the lowest（342.9）. CONCLUSIONS ：The hospital pharmacist post value evaluation model constructed by factor counting method can provide a scientific and reliable theoretical basis for realizing the rewards of different positions in the dispensing department.  
        关键词：Factor counting method;Pharmacist post;Value evaluation;Performance management   
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      • ZHU Yurong,LONG Xin,WANG Zheng,CHENG Kai,CHEN Yanshen,LIU Hua,FENG Weiyi
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To understand the situation of healthcar e workers’occupational exposure of hazardous drugs （chemotherapeutic drugs and antiviral drug ）and relative cognition level ，and to provide reference for improving the level of occupational protection. METHODS ：During Oct. 2018 to Mar. 2019，healthcare workers from 12 hospitals of different levels and different departments in Shaanxi province were selected as respondents to conduct a self-designed questionnaire survey. Information we surveyed contained baseline characteristics ，hazardous drugs exposure ，physical health status ，and occupational protection. Valid questionnaires were collected and analyzed statistically. RESULTS ：A totally of 1 848 questionnaires were sent out ，and 1 767 questionnaires were collected ，including 95 were pharmacists ，100 were physicians ，and 1 572 were nurses. The frequency of diarrhea and menstrual disorders in healthcare workers with long-term exposure to antiviral drugs （antiviral drug exposure group ） and cross-exposure to antiviral drugs and chemotherapeutic drugs （cross-exposure group ）were significantly higher than unexposed group （P＜0.05）. The incidence of routine blood abnormalities in cross-exposure group ，antiviral drug exposure group and healthcare workers with long-term exposure to chemotherapy drugs （chemotherapy drug exposure group ） was higher than unexposed group by 9.13％，5.50％ and 12.34％，respectively. 84.7％ of the respondents had little knowledge of hazardous drugs ， and 8.15％ of the respondents had never received occupational protection training. Additionally ，the ratio of healthcare workers receiving occupational protection training in the cross-exposure group was significantly higher than unexposed group （P＜0.05）， and the ratio of healthcare workers receiving occupational protection training in antiviral drug exposure group were significantly lower than unexposed group （P＜0.05）. CONCLUSIONS ：Long-term exposure to hazardous drugs will cause certain occupational hazards to healthcare workers. It is necessary to improve healthcare workers ’awareness of self-protection ，increase the input of hospitals in occupational protection training and establish occupational protection standards in order to improve the current situation of occupational protection of healthcare workers.  
          
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      • LIU Jinglin,WU Chunnuan,SONG Xiaokun
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To study the abnormal use of anti-tumor dr ugs i n the clinic in order to provide reference for rational use of drugs in the clinic. METHODS ：Referring to foreign and domestic anti-tumor drug use guidelines and literatures ，Guidelines for Clinical Use of New Anti-tumor Drugs （2018 edition），Off-label Drug Use List （2019 edition），Practical Oncology （secondary edition），anti-tumor drug package inserts approved by FDA and package inserts of anti-tumor drug listed in China ，abnormal use of antitumor drugs （including instructions ，special indications ，and the order of administration of new anti-tumor drugs ） was summarized and analyzed. RESULTS & CONCLUSIONS ：The off-label use of anti-tumor drugs were summarized in this paper ， including 11 drug varieties and 4 kinds of off-label drug items ，such as off-label drug use plan （recombinant human endostatin ， rituximab），off-label administration route （pemetrexed disodium ，bortezomib，bevacizumab），off-label administration lines （erlotinib，gefitinib），off-label drug dosage （actinomycin D ，gemcitabine，ifosfamide，etoposide）. They should be carefully selected and strictly monitored in clinical use ，and treatment plan should be adjusted according to needs. Among the special indications，cyclophosphamide，cytarabine，methotrexate and cisplatin were used in large doses ，which were 2 000-2 400 mg/m2， 2 000 mg/m2，12 g/m2 and 80-120 mg/m2，respectively；individual differences should be paid attention to and therapeutic drug monitoring should be carried out if necessary. In the scheme of combination of new anti-tumor drugs or traditional chemotherapy drugs，there were 5 categories and 11 items in total ，such as combination of molecular targeted anti-tumor drugs with traditional chemotherapy drugs （such as docetaxel at first ，gefitinib at the same time or later ），combination of target immunocheckpoint drugs with traditional chemotherapy drugs （such as platinum at first ，then nivolumab ），and molecular targeted anti-tumor drugs combination（such as pertuzumab and trastuzumab should be given in sequence ，in either order ）. In clinical use ，histopathological diagnosis should be made clear ， and drugs with specific targets should be used after gene detection and strictly follow the indications.  
        关键词：Anti-tumor drugs;Abnormal drug use;Off-   
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      • ZONG Yutong,YAN Suying,CHU Yanqi
        Vol. 31, Issue 7, (2020)
        摘要：OBJECTIVE：To summari ze clinical application and existing problems of artificial auditing and information-based medical order auditing modes so as to provide reference for improving rational medication. METHODS ：Collecting data by literature search ，using “Prescription auditing ”“Medical order auditing ”“Prescription pre-auditing ”“Medication error ” “Medication-related problems ”“Medication safety ”“Alert fatigue ”“Medication review ”“Decision support medication review ” “Real-time medication review ”“Real-time prescription surveillance ”“Clinical alarms decision support systems ”“Clinical pharmacy information systems ”“Medication errors ”“Medication related problem ”as keywords ，the related literatures from Jan. 2000 to Nov. 2019 were retrieved from CNKI ，Wanfang database ，PubMed，Embase，Web of Science and other databases. The clinical application and existing problems of 2 medical order auditing modes were analyzed and summarized. RESULTS & CONCLUSIONS：The artificial auditing mode can reduce medication-related problems （such as poor drug treatment effect ， untreated symptoms or indications ，potential adverse drug events ，unnecessary drug treatment ，etc.），improve life quality of patients，but can not decrease the mortality and the length of hospitalization stay ；there are some problems ，such as many pharmacists needed for medical order auditing ，insufficient auditing time ，different auditing standards ，auditing time lagging. The information-based medical order auditing mode can reduce medication-related problems ，save auditing time ，reduce the incidence of medication errors ，reduce unreasonable medical orders ，and improve audit efficiency. Compared with the artificial auditing mode ，it has certain advantages ，but there are problems such as alarm fatigue. At present ，the domestic medical order auditing mode is dominated by artificial audit mode ；the information-based medical order auditing mode is still in the initial stage ，and the most attention is paid to its influence on the qualified rate of prescription ，while the research on the incidence of adverse events and other clinical effects is less. Later ，the 2 midical order can be D181100000218002）； improve to provide a reference for medical order auditing of 2019 hospital pharmacy personnel.  
          
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