最新刊期
      卷 31 ， 期 12 ， 2020
      • REN Lei,ZHANG Liyang,HAN Dan,CHAI Yifeng,ZHANG Li,SHU Lixin
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To provid e foreign experience for the improvement of sympathetic drug use system in China. METHODS：Australia’s Special Access Scheme （SAS） was introduced and analyzed in respects of applicant ，drug scope ， application method ，processing flow ，main responsibilities ，drug payment and other specific content. The suggestion were put forward for the improvement of sympathetic drug use system in China. RESULTS & CONCLUSIONS ：Therapeutic Goods Administration（TGA）divided SAS into 3 channels according to disease severity and drug safety ，the patients with very urgent medical conditions could use drugs directly through SAS-A channel ，and unapproved drugs with relatively high safety can also be used directly through SAS-C channel after informing TGA ；in other conditions ，drugs can be used through SAS-B channel by the form of “application-evaluation”after approved by TGA. At the same time ，Australia has made detailed regulations on the responsibilities of doctors ，government regulators and sponsor in the system ，forming a relatively perfect system. In order to improve compassionate use system ，improve the feasibility of drugs ，make drug research and development results more timely benefit clinical ，it’s suggested that we should establish multiple application channels ，construct the multi-level drug evaluation system and connect with the existing system well.  
        关键词：Australia;Special Acce ss Scheme;Sympathetic drug use system   
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        发布时间：2022-06-21
      • YAO Yi,ZHAO Yanjiao,FAN Xin,CHEN Yongfa
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To provide reference for further improving the establishment of drug registration applicant compliance management organizations in China. METHODS ：Through introducing and analyzing the establishment ，responsibility configuration and operation mechanism of drug registration applicant compliance management organizations in the United States ，the suggestions were put forward for improving the establishment of drug registration applicant compliance management institutions in China. RESULTS & CONCLUSIONS ：There were two levels of compliance management organizations for drug registration applicant in the United States ；at Office of the Commissioner of FDA level ，the Compliance Policy Council was responsible for ensuring consistency in the implementation of all compliance policies in the FDA regulated area ；at the level of Center for Drug Evalution and Research （CDER）and Office of Regulatory Affairs （ORA），the compliance management function was mainly undertaken by Office of New Drugs （OND），Office of Generic Drugs （OGD），Office of Compliance （OC） and Office of Communication （OCOMM）under CDER ，as well as Office of Policy and Risk Management （OPRM），OC，Office of Bioresearch Monitoring Operations（OBIMO）and Office of Pharmaceuticl Quality Operations （OPQO）under ORA ，which were responsible for developing compliance documents and procedures ，carrying out compliance education ，compliance guidance ，compliance inspection and punishment for violations. Before submission stage of drug registration application ，the compliance education function of OC and the compliance guidance function of OND/OGD played an important role ；in the application submission stage ，OND/OGD was responsible for the compliance review of application materials ；in the stage of reviewing the application materials ，OND/OGD and OC of CDER ensured drug compliance through collaboration with OC ，OBIMO and OPQO of ORA. The establishment of drug registration compliance management institutions in China was still in the preliminary exploration stage. It is suggested that China can learn from the relevant experience of the United States ，establish a multi-level or ganization structure ，set up an independent compliance education department ， and strengthen thecooperation between evaluation department and compliance inspection department ，and to improve the level of compliance management of drug registration applicants in China.  
          
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        发布时间：2022-06-21
      • WANG Yifang,YANG Lina,YANG Yue
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To provide applicable suggestions for exploring the establishement of the vaccination rare adverse reactions compensation fund in China. METHODS ：Through literature research and regulation review ， the establishment background，compensation principle ，management and operation mode （including management methods ，source，uses and risk control measures）of Vaccine Injury Compensation Trust Fund in the United States were introduced in details ，while the operation effect was evaluated ，and the suggestions for the establishment of the vaccination rare adverse reactions compensation fund in China were put forward. RESULTS & CONCLUSIONS ：The U.S. National Vaccine Injury Compensation Program （VICP）imposed a certain proportion of vaccine excise tax on each dose of vaccine sold by vaccine companies ，and established the Vaccine Injury Compensation T rust F und as its fixed source of compensation funds to provide compensation for vaccine victims. The fund belonged to the special needs trust. When the vaccine victims met the compensation conditions ，they can convert their compensation rights into the beneficial rights under the trust law. The fund was managed by the Fund Management Branch under U.S. Dept. of the Treasury，and it took a variety of risk control measures such as capital guaranteed investment ，subrogation，emergency preparedness. As of 2018，a large number of fund balances had been accumulated ，which was sufficient to ensure the solvency of VICP. It is suggested that China fully learn from the successful experience of the Vaccine Injury Compensation Trust Tund of the United States ， based on the domestic reality ，start from improving the relevant legislation of the compensation fund ，building the compensation management system ，making clear the source and usage of the fund ，taking various risk control measures ，so as to explore the establishment of China ’s vaccination rare adverse reactions compensation fund ，further expand the financing channels ，stabilize the source of funds ，and improve the compensation effect.  
          
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        发布时间：2022-06-21
      • XUE Yan,LIU Xinyuan,GAO Hongbo,XUE Yongzhi
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To study the anti-inflammatory effects of water extract from Inner Mongolia medicine Agi （i. e. the aerial part of Artemisia frigida ），and to preliminarily explore its mechanism. METHODS ：Totally 60 mice were randomly divided into model control group （water），aspirin group （positive control ，0.4 g/kg），Agi water extract high-dose ，medium-dose and low-dose groups （60.0，30.0，15.0 g/kg，by crude medicine ），with 12 mice in each group. After intragastric administration for consecutive 5 d，the ear swelling of mice was induced by 2，4-dinitrochlorobenzene. Another 60 mice were grouped and admini- stered by the same way ，and the foot swelling of mice was induced by carrageenan. The ear swelling degree and inhibitory rate ， paw swelling rate were calculated to evaluate the anti-inflammatory effect of Agi water extract. The contents of TNF-α，IL-1β and PGE2 in plantar inflammatory tissue induced by carrageenan in mice were determined by ELISA. The content of MDA was determined by thiobarbituric acid trace method and NO by nitrate reductase method. RESULTS ：Compared with model control group，the degrees of ear swelling of mice were decreased significantly in aspirin group and Agi water extract high-dose ， medium-dose，low-dose groups （P＜0.05 or P＜0.01），and the inhibitory rates of ear swelling were 72.3％，71.1％，52.6％， 36.8％，respectively；the paw swelling rates of mice in aspirin group and Agi high-dose，medium-dose groups were decreased significantly，while those were decreased significantly in Agi water extract low-dose group 0.5 h and 4.0 h after inducing inflammation（P＜0.05 or P＜0.01）；the contents of TNF-α，IL-1β，PGE2，NO and MDA in plantar inflammatory tissue of mice in aspirin group and Agi water extract high-dose ，medium-dose groups were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：Inner Mongolia medicine Agi water extract has obvious anti-inflammatory effects on ear swelling induced by 2，4-dinitrochlorobenzene and paw swelling induced by carrageenan ，and its mechanism may be related to the inhibition of TNF-α， IL-1β and PGE2 generation，the reduction of NO and MDA excessive release in inflammatory tissues.  
          
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        发布时间：2022-06-21
      • TIAN Xulu,LAN Cheng,CEN Yunguang,WANG Taihao,CUI Xiaoyan
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To explo re the dose-effect relationship and mechanism of protective effects of total asiaticoside （TA） on gastrointestinal motility and enteric nervous system （ENS）in aged functional dyspepsia （FD）model rats. METHODS ：Aged male SD rats of 16 months old were randomly divided into blank control group ，model group ，TA low dose ，medium dose and high dose groups （15，30，60 mg/kg），with 8 rats in each group. FD model was established by tail-stimulation combined with irregular diet for 4 weeks. The next day after modeling ，administration groups were given relevant doses of TA solution intragastrically ； control group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 15 d. Gastric emptying rate and small intestinal propulsion rate of rats were examined. ELISA were used to detect serum contents of MTL and VIP. Immunofluorescence and immunohistochemistry were proposed to measure the expression of ENS marker （S100β and GDNF）in gastric antrum tissue. The protein expression of S 100β，GFAP，PGP9.5，GDNF，p-MEK and p-ERK 1/2 in gastric antrum tissue were measured by Western blotting assay. RESULTS ：Compared with blank control group ，gastric emptying rate and small intestinal propulsion rate ，serum MTL content and protein expression of PGP 9.5 in gastric antrum tissue of model and TA low，medium dose group were decreased significantly ，while serum VIP content ，protein expressions of S 100β，GFAP，GDNF， p-MEK and p-ERK 1/2 in gastric tissue were increased significantly （P＜0.05）. Compared with model group ，gastric emptying rate and small intestinal propulsion rate of TA groups were increased significantly （P＜0.05）；except for GFAP protein in TA low dose group（P＞0.05），the serum MTL content and the expression of PGP 9.5 protein in gastric antrum tissue of rats in TA groups were increased significantly ，while serum VIP content ，protein expression of S 100β，GFAP，GDNF，p-MEK and p-ERK 1/2 in gastric antrum tissue were decreased significantly （P＜0.05）. Some or most of the content of gastrointestinal motility indexes and related factor protein expression were significantly different among TA groups （P＜0.05），and the indexes in TA high dose group could recover to the levels which were not significantly different with blank control group （P＞0.05）. CONCLUSIONS ：TA can dose-dependently improve the gastrointestinal motility deficiency and ENS dysfunction in aged FD model rats ，especially in high dose（60 mg/kg）of TA group. Its mechanism may be related with promoting the release of endogenous MTL ，inhibiting the secretion of VIP ，expression of GDNF and the activation of downstream signaling pathway ，and promoting the repair of ENS and intestinal neurons.  
          
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        发布时间：2022-06-21
      • WU Yingying,LEI Yan,YAO Chengfen,MA Xue,HUANG Yong,LI Yongjun,LIN Changhu
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To establish a metho d for sim ultaneous determination of 8 flavonoid glycosides in Sedum bulbiferum . METHODS：HPLC method was adopted to determine the contents of kaempferol- 3-O-β-D-glucopyranoside-（1→2）-α-L-glucopy- ranoside-7-O-α-L-glucopyranoside（KGGR），kaempferol-3-O-β-D-glucopyranosyl-7-O-α-L-rhamnopyranoside（KGR），quercetin-3- O-α-L-rhamnose-7-O-α-L-rhamnoside（QRR），BulbiferumosideⅡ，kaempferol-3-O-（6-coumarinyl）-β-D-glucose-（1→2）-β-D-glu- cose-7-O-α-L-rhamnoside（KcGGR），kaempferol-3-O-（2-β-D-glucose）-α-L-rhamnose-7-O-α-L-rhamnoside（KGRR），kaempferol-3- O-α-L-rhamnoside-7-O-α-L-rhamnoside（KRR），kaempferol-3-O-（6″-acetyl-β-D-glucose）-7-O-α-L-rhamnoside（KaGR）in S. bulbi- ferum. The determination was performed on Waters CORTECS C 18 column with mobile consisted of acetonitrile - 0.1％ phosphoric acid water solution （gradient elution ）at the flow rate of 0.8 mL/min. The detection wavelength was set at 254 nm，and column temperature was 35 ℃. The sample size was 5 μL. RESULTS：The linear range of 8 constituents were 0.013-0.052，0.005-0.018， 0.008-0.031，0.010-0.042，0.009-0.038，0.008-0.030，0.009-0.037，0.032-0.130 μg，respectively（all r were not less than 0.999 0）. The limits of detection were 0.08，0.14，0.11，0.21，0.42，0.35，0.23，0.28 μg/mL，respectively. The limits of quantification were 0.25，0.47，0.38，0.69，1.40，1.17，0.77，0.93 μg/mL，respectively. RSDs of precision ，reproducibility and stability tests （24 h） were all lower than 3％（n＝6 or n＝7）. The average re coveries were 99.67％-104.20％（RSDs＝0.17％-1.59％，n＝6）. Average contents of above 8 constituents in 13 batches of samples were 0.893 8，0.312 6，0.490 8，0.964 9，0.751 2，0.502 2，0.606 2， 1.915 7 mg/g（n＝3）. CONCLUSIONS ： The method is simple， acourate and reproducible ， and can be used for simultaneous determination of 8 flavonoid glycosides in 才〔2016〕5677） S. bulbiferum .  
          
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        发布时间：2022-06-21
      • QIN Zhenmiao,ZHANG Lili,CHEN Demei,WANG Ning,CHEN Yingzi,WU Xinfu,ZHANG Junqing
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To explore the potential active ingredients and mechanism of Alpinia officinarum in the treatment of gastric ulcer. METHODS ：By network pharmacology method ，the active ingredients and action targets of A. officinarum were screened through TCMSP and TCMID database retrieval [oral bioavailability （OB）≥30％ and drug like （DL）≥0.18] and literature mining. Targets of gastric ulcer were obtained in the TTD ，CTD，OMIM，PubMed，DrugBank and DisGeNet databases. Venny 2.1 software was used to screen common targets for the active ingredients of A. officinarum and gastric ulcer. Then ，the protein-protein interaction（PPI）of the common targets was obtained by STRING database ，and the PPI network was constructed and analysed by using Cytoscape 3.7.1 software. GO function and KEGG pathway enrichment analysis of the common targets were performed by using ClusterProfiler R package. Finally ，Cytoscape 3.7.1 software was used to construct and analyze the network diagram of “active ingredients-targets-pathways ”. RESULTS ：Totally 19 active ingredients of A. officinarum ，209 active ingredients targets and 195 gastric ulcer related targets ，involving 35 common targets ，were screened out. The average node degree of PPI network of common targets was 18，and the average intermediate number was 16.9. There were 11 key targets ，i.e. PTGS2，VEGFA，IL6， IL1B，CCL2，MYC，MMP9，EGFR，HIF1A，ESR1，BCL2L1. The common targets were mainly concentrated in the cell constituents such as the platelet α granule lumen and mitochondria outer membrane ，involved in the biological processes as oxidative stress ，inflammatory response regulation ，and molecular functions as protein phosphatase binding ，growth factor receptor binding. They were also enriched in the signal pathways such as PI3K/Akt，HIF-1. The network of“active ingredients- targets-pathways”showed the active ingredients such as quer- cetin，apigenin，kaempferol and galangin in A. officinarum played an anti-gastric ulcer effect by acting on PTGS2，NOS2， BCL2， IL6， VEGFA， IL1B， MMP9， BCL2L1 and other targets to jointly regulate PI 3K-Akt，HIF-1，TNF，IL-17， NF-κB and other cell proliferation，angiogenesis，and infla- 163.com mmation related pathways. CONCLUSIONS ：A. officinarum shows anti-gastric ulcer effect with the characteristics of multi-ingredient ，multi-target and multi-path.  
        关键词：Network pharmacology;Alpinia officinarum;Gastric ulcer;Active ingredients;Mechanism   
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        发布时间：2022-06-21
      • LI Ying,TAO Zhuping,CHANG Xu,OU Hongli,JIANG Lun,LI Canwei,TANG Yanlong,ZHOU Yue,BAI Li,GAO Pengfei
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To preliminarily study the antitumor mechanism of Periplaneta americana extract C Ⅱ-3 on MFC tumor-bearing mice. METHODS ：Balb/c mice were randomly divided into model group （normal saline 20 mL/kg）and C Ⅱ-3 group （200 mg/kg），with 6 mice in each group. MFC cell suspension （0.2 mL）was injected under the right armpit of mice. On the next day，mice were given relevant medicine intragastrically ，once a day ，for consecutive 10 d. 24 h after the last administration ，Based on the measurement of tumor size ， 1H-NMR technology combined with unsupervised PCA ，supervised PLS-DA and OPLS-DA were used to compare metabolic spectrum of liver tissue from tumor-bearing mice of 2 groups，to analyze differential metabolites and to explore the potential antitumor mechanis m of C Ⅱ -3. RESULTS ：Compared with model group ，the tumor body was significantly reduced in tumor-bearing mice of C Ⅱ-3 group. There were differences in 1H-NMR spectra between the 2 No.81960712）； groups. According to unsupervised PCA ，supervised PLS-DA and OPLS-DA ，totally six potential differential metabolites ，as glycogen （increased），pyruvate （decreased），arginine （de- creased），hydroxyproline （increased），inosine （increased） and niacinamide （increased），were identified in the liver tissue，which were mainly attributed to the metabolism of arginine ，energy and nucleic acid. CONCLUSIONS：The anti tumor effect of C Ⅱ-3 may be related to the regulation of arginine metabolism ，energy metabolism and nucleic acid metabolism.  
        关键词：Periplaneta americana extract C Ⅱ-3;MFC cell line;Metabolomics;1H-NMR;Mice   
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        发布时间：2022-06-21
      • WU Tingting,ZHANG Yu,DU Yao,CHEN Rui,WANG Lili,PENG Hongman,TANG Lei,WANG Ying,ZHANG Jiquan
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To investigate th e stabilities of antitumor candid ate Gedatolisib in plasma in vitro and simulated gastric/intestinal fluids ，and to analyze the possible catabolites in plasma. METHODS ：HPLC method was adopted. Using indometacin as internal standard ，the contents of Gedatolisib incubated in plasma of SD rats （male）for 0，0.5，1.0，1.5，2.0，3.0 h and blank simulated gastric fluid （pH 1.3，no enzyme ），blank simulated intestinal fluid （pH 6.8，no enzyme ），simulated gastric fluid（pH 1.3，containing pepsin ）and simulated intestinal fluid （pH 6.8，containing trypsin ）for 0，0.5，1.0，2.0，3.0，4.0，6.0 h were determined. The remaining percentage of Gedatolisib was calculated. UPLC-Q-TOF/MS was used to analyze the TIC of blank plasma and incubated samples. The differential peaks were compared， and catabolites were inferred by MS 1Z073）.gzwjkj2019-1- chromatograms. RESULTS ： The remaining percentage in plasma of rats for 2.0 h was about 63％，and there was nosignificant change after continued incubation. The remaining percentage of Gedatolisib incubated in blank simulated intestinal fluid for different time ranged （99.18 ± 2.15）％ -（103.20 ± 3.41）％ . The remaining percentage in simulated com intestinal fluids for 2.0 h ranged （88.76 ± 1.53）％ . The remaining percentage in blank simulated gastric fluids for 2.0 h was ranged （85.63±1.55）％，and there was no significant change after continued incubation. The remaining percentage in simulated gastric fluid was from （94.94±3.52）％（0 h）to（16.19±1.17）％ （6.0 h）. TIC of UPLC-Q-TOF/MS showed that the differential peaks of incubated samples and blank plasma was 6.42 min under positive mode scanning ，molecular ion peak of m/z 616.335 1，simulated 632.327 7，630.317 0，602.278 6 [M+H]+ could be found in scanning channel. It was speculated that Gedatolisib could generate 1-（4-（3-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N，N-dimethylpiperidin-4-amine oxide ，1-（4-（4-（dimethylamino）piperidine-1-carbonyl）phenyl）-3-（4-（4-morpholino-6- （3-oxomorpholino）-1，3，5-triazin-2-yl）phenyl）urea and 1-（4-（3-（4-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N-methylpiperidine. CONCLUSIONS ：Gedatolisib is not stable in rat plasma ，and it may undergo terminal N oxidation， morpholine ring oxidation and terminal N demethylation. Gedatolisib is stable in artificial intestinal fluid and blank artificial gastric/ intestinal fluid ，and degrades obviously in the presence of pepsin.  
        关键词：Antitumor candidate;Gedatolisib;Plasma;Simulated gastric fluid;Simulated intestinal fluid;Stability;Catabolite   
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        发布时间：2022-06-21
      • LIU Liqin,PENG Xiao,MA Xue,LI Yongjun,LIU Chunhua,PAN Jie,WANG Yonglin,WANG Aimin
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To provide reference for improving the quality standard of Rhizoma Bego niae from Guizhou . METHODS：Five batches of Rhizoma Begoniae from Guizhou were collected ，and the microscopic characteri stics of the Rhizoma Begoniae powder were observed. According to the corresponding methods in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）， potent adenosine 50-triphosphate competitive phosphati - dylinositol-3-kinase/mammalian target of rapamycin inhibitors：discovery of compound 26（PKI-587），a highly effi cacious dual inhibitor Morpholine as a privileged structure ：a review on the me - dicinal chemistry and pharmacological activity of morpho - line containing bioactive molecules[J]. Med Res Rev ， qq.com 2019. DOI ：10.1002/med.21634. qualitative identification of Rhizoma Begoniae was conducted by TLC ，and the contents of moisture ，total ash and water-soluble extract in Rhizoma Begoniae were determined. The contents of rutin were determined by HPLC. RESULTS ：The powder of Rhizoma Begoniae medicinal materials was brown ，stone cells were square ，polygonal-like or irregular. There were many starch grains and few complex grains. The conduit ，calcium oxalate square crystal/cluster crystal were visible. The same fluorescence spots were found in the same location of TLC atlas of Rhizoma Begoniae control herb. The moisture ，total ash ，water-soluble extract contents were 10.15％-11.41％，8.70％-12.59％ and 16.91％-19.58％，respectively. The linear range of rutin were 18.47-147.8 μg/mL （r＝0.999 8）；RSDs of reproducibility ，intermediate precision and stability tests （8 h）were all lower than 3.0％；the average recoveries were 99.39％-100.29％（RSDs were 0.23％-2.59％，n＝3）；the contents of rutin in 5 batches of Rhizoma Begoniae were 0.102％-0.198％. CONCLUSIONS ：The contents of moisture and total ash shall not exceed 13.0％ and 14.0％ respectively， and the contents of water-soluble extract and rutin shall not be less than 15.0％ and 0.080％. The quality standard established in this study can be used for the quality control of Rhizoma Begoniae from Guizhou.  
          
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        发布时间：2022-06-21
      • LYU Beibei,YANG Haiyuan,CHENG Hua,WEI Wenzhi,ZHANG Minjuan
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To evaluate the dissolution behavior consistency between the generic drugs and original drugs of Oxcarbazepine scored tablets ，and to compare the appearance ，the friability of the split portions ，loss of mass of the split portions as well as crystal form and morphology of raw material from different enterprises. METHODS ：HPLC method was adopted. The paddle method （rotation speed of 60 r/min，the temperature of 37.0℃）was adopted to determine accumulative dissolution rate of generic and original drugs in 4 mediums [ 0.6％ SDS hydrochloric acid solution （pH＝1.2），0.6％ SDS acetate buffer solution （pH＝4.5），0.6％ SDS phosphate buffer solution （pH＝6.8）and 0.6％ SDS water solution]. The similarity factor method was used to evaluate the similarity of dissolution curves as well as intra-batch uniformity of the split portions and whole tablets. The friability tester and electronic balance were used to determine the friability and the loss of mass of the split portions. X-ray diffractometer and scanning electron microscope were used to observe the crystal form and crystal morpho logy of the raw materials of different enterprises. RESULTS ：The linear range of oxcarbazepine was LOD was 0.04 μg/mL；RSDs of precision ，stability，reprodu- cibility and durability tests were lower than 2.0％；the reco- veries were 99.80％-101.63％（RSD＝0.37％-0.91％，n＝3）. The average cumulati ve dissolution rate of generic drug A ， generic drug B and original drug in 4 different dissolution media at 90 min were 92％，87％，90％ [0.6％ SDS hydrochloric acid solution（pH＝1.2）]；94％，94％，90％ [0.6％ SDS acetate buffer solution （pH＝4.5）]；95％，95％，91％ [0.6％ SDS phosphate buffer solution （pH 6.8）]；97％，98％，95％（0.6％ SDS water solution ）. The similarity factors of generic drug A ，generic drug B and original drug in 4 kinds of different dissolution media were 66 and 81，71 and 69，71 and 61，59 and 39. In the first 15 min，the difference of dissolution rate of split portions and whole tablets were －3％-13％，－2％-24％ and －3％-7％ for generic drug A ， generic drug B and original drug ，respectively. RSDs of accumulative dissolution rate of split portions and whole tablets were 6％-14％ and 2％-9％ for generic drug A （n＝12），4％-10％ and 1％-8％ for generic drug B （n＝12）and 2％-7％ and 2％-8％ for original drug. The appearance of the original drug was fusiform ，and the notch was deep ；the shape of the generic drug was different from each other ，and the notch of the generic drug was significantly shallower than that of original drug. The friability ， the loss of mass of the split portions for generic drug A and generic drug B ，original drug were 0.62％and 0.67％，0.12％ and 0.11％，0.08％ and 0.05％. The domestic raw materials possessed irregular lumps and debris ，while the raw materials produced by original drug enterprises possessed regular flat cuboids and regular strips with little debris ；but X-ray diffraction peaks of them were basically the same. CONCLUSIONS ：The dissolution behavior of generic drug A in 4 medium is consistent with that of the original drug；dissolution behavior of generic drug B in water containing 0.6％SDS is different from that of the original drug ；there is no significant change in the homogeneity of the original drug before and after splitting ，but the homogeneity of the generic drug A and B after splitting is lower than that of the whole tablet ；the fragility of generic drugs and loss of mass of split portions are higher than those of the original drugs ；two kinds of raw material have the same crystal form but different crystal morphology.  
        关键词：Oxcarbazepine;Dissolution behavior;Scored tablets;Generic drug;Original drug;Consistency evaluation;HPLC   
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      • LI Yan,PAN Yanfan,ZHANG Tao,HAN Zhongyao
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To optimize the extraction technology of Senecio scandens ，and to provide reference for the further development and utilization of the medicinal material. METHODS ：The method of reflux extraction with 80 ℃ water bath was used to extract S. scandens . HPLC method was adopted to determine the contents of chlorogenic acid and hyperoside. The determination was performed on Diamonsil C 18 with mobile phase consisted of 0.2％ glacial acetic acid water solution-methanol （82∶18，V/V）at the flow rate of 1.0 mL/min；the column temperature was set at 35 ℃；the detection wavelength was 327 nm，and the sample size was 5 μL. UV-Vis spectrophotometry was used to determine the contents of total flavonoids（by rutin ）and total alkaloids （by matrine）and the detection wavelengths were set at 509 nm and 208 nm，respectively. Based on single factor tests ，using ethanol volume fraction （A，％），solvent folds （B，mL/g），extraction time （C，h），extraction times （D，times）as factors ，using the contents of chlorogenic acid ，hyperoside，total flavonoids and total alkaloids as indexes ，and t he weight coefficients of above indicator components were calculated based on information entropy weighting method so as to calculate their comprehensive scores ， then L 9（34）orthogonal design was used to further optimize the extraction technology. The validation tests were also performed. RESULTS：The optimal extraction technology of S. scandens included that 8-fold 50％ ethanol，extracting for 3 times，lasting for 1.5 h each time. Results of 3 times of validation tests showed that RSDs of the contents of chlorogenic acid ，hyperoside，total flavonoids and total alkaloids were all lower than 1.5％（n＝3）. CONCLUSIONS ：The optimized technology is reproducible ， stable and feasible ，and can be used for the extraction of S. scandens .  
          
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      • WANG Xue,WANG Li,LIAO Xiu,WANG Haibo,YANG Juan,LI Qiji,YANG Xiaosheng
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE： To compare the contents of 4 components and toxicity from Miao medicine Chimonanthus nitens samples after drying in the shade ，oven drying ，steam，charring. METHODS ：The contents of scopolin，fraxin，scopoletin and isofraxin were simultaneously determined by HPLC. The separation was performed on Welch-C18 column with mobile phase consisted of acetonitrile-water （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 214 nm，and column temperature was 30 ℃，and the sample size was 10 μL. Modified Karber method was used to determine the LD 50 and its 95％CI of different processed C. nitens to mice and evaluate its acute toxicity. RESULTS ： The linear range of scopolin ， fraxin， scopoletin and isofraxin were 0.019-1.856，0.016-1.616，0.009-0.920，0.006-0.624 μg（R2 were all not lower than 0.999 5）. RSDs of precision ， stability and reprodu-cibility tests were all lower than 2.0％（n＝6）. The average recoveries were 104.49％，102.22％， 101.45％，99.26％（all RSDs were lower than 2％，n＝6）. The contents of scopolin were 1.119 0％，0.904 3％， 1.068 4％and 0.036 4％；those o f fraxin were 0.867 8％，0.453 9％，0.423 7％and 0.020 5％；those of scopoletin ； those of isofraxidin were 0.110 2％，0.202 1％，0.208 1％ and 0.249 4％in samples after drying in the shade ，oven CX-2018-001） drying， steam， charring. The LD 50 of 4 processedproducts were 4 118.13，3 733.36，1 643.61，＞10 000 qq.com mg/kg samples ；95％CI were （3 748.87，4 523.76）， （3 422.16，4 072.86），（1 520.90，1 776.23），（＞10 000） mg/kg. CONCLUSIONS ：HPLC method is reproducible and precise. It can be used to determine the contents of 4 components in different processed products of C. niten s. The contents of 4 components in different processed products ， and the contents of glycosides toxicity components are decreased significantly. All the 4 processed products were low or non-toxic.  
        关键词：Chimonanthus nitens;Processing;Content;Acute toxicity;Glycosides;Mice   
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      • LI Yuan,LI Xiuli,WANG Shu,WANG Xin,CAO Guangshang,SUN Ping,GUO Gongling
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To establish HPLC fingerprint of different products of suet oil-baked Epimedium brevicornum ，and to screen the optimal baking technology. METHODS ：HPLC method was adopted. Using icariin as reference ，HPLC fingerprints of 22 batches of samples were drawn. The similarity was evaluated by using Similarity Evaluation System of TCM Chromatographic Fingerprint（2012 edition），and common peaks were confirmed. HCA ，PCA and OPLS-DA analysis were performed by SIMCA 14.1 statistical software. Taking variable importance in the project ＞1 as criteria ，biomarkers affecting the quality difference of suet oil-baked E. brevicornum were screened ；using mass marker as index ，the baking technology was screened by baking technology. RESULTS：There were 18 common peaks in 22 batches of samples. The similarities were between 0.831 and 0.991. Totally 7 common peaks were identified ，i.e. epimedin A ，epimedin B ，epimedin C ，icariin，sagittatoside A ，sagittatoside B ，baohuoside Ⅰ. The 22 batches of samples were clustered into two categories ，S19-S22 were clustered into category Ⅰ and S 1-S18 were clustered into category Ⅱ. The category Ⅱ was sub-clustered into category Ⅱa（S15-S18），category Ⅱb（S10-S14），category Ⅱc （S1-S9）；the result of PCA analysis was consistent with above results. OPLS-DA showed that the biomarkers affecting the quality difference were icariin ，sagittatoside B and baohuoside Ⅰ. The results of kinetic studies showed that the content of icariin when baked at 180 ℃ for 25 min or 190 ℃ for 20 min，that of baohuoside Ⅰ when baked at 180 ℃ for 30 min or 190 ℃ for 15 min and that of epimedin B when baked at 210 ℃ for 18 min were the highest ；according to above results ，the optimal baking technology was baking at 180 ℃ for 25-30 min or 190 ℃ for 15-20 min. CONCLUSIONS ：Established fingerprint is stable ， reliable and reproducible. The multivariate statistical analysis can be used for the changes of chemical components in E. brevicornum under different baking condition and preliminary selection of baking technology.  
        关键词：Epimedium brevicornum;Suet oil-based;HPLC;Fingerprint;Multivariate statistical analysis;Optimization of   
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      • TANG Guiju,TIAN Yuan,WANG Jiting,SU Song,LI Yaling
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To systematically evaluate the efficacy an d s afety of apatinib combined with transcatheter arterial chemoembolization（TACE）in the treatment of moderate and advanced liver cancer ，and to provide evidence-based reference for rational drug use in the clinic. METHODS ：Retrieved from Cochrane Library ，Embase，PubMed，Web of Science ，SinoMed， CNKI，Wanfang，VIP database ，RCTs about apatinib combined with TACE （trial group ）versus TACE （control group ）in the treatment of moderate and advanced liver cancer were collected from inception to Sep. 2019. After screening the literature and extracting the data ，the quality of included literatures was evaluated by using bias risk assessment tool recommended by the Cochrane system evaluator manual 5.1.0 and the modified Jadad scale. Meta-analysis was carried out by using Stata 12.0 software. RESULTS：Totally 16 RCTs were included ，involving 1 043 patients. Results of Meta-analysis showed that objective response rate [OR ＝3.10，95％CI（2.38，4.03），P＜0.001]，disease control rate [OR ＝3.56，95％CI（2.62，4.83），P＜0.001] and survival rate [OR ＝2.40，95％ CI（1.86，3.10），P＜0.001]，the incidence of diarrhea [OR ＝2.27，95％ CI（1.21，4.24），P＝0.011]， hypertension [OR ＝6.97，95％ CI（1.21，40.15），P＝0.030]， proteinuria [OR ＝12.44，95％CI（2.51，61.71），P＝0.002] and com hand foot syndrome [OR ＝32.50，95％CI（12.03，87.77），P＝ 0.001] of trial group were significantly higher than those of control group. The serum level of VEGF [SMD ＝－ 3.64， 95％CI（－5.06，－2.22），P＜0.001]，MMP-9 [SMD＝－3.21，95％CI（－4.31，－2.10），P＜0.001]，AFP [SMD ＝－3.54， 95％CI（－7.03，－0.06），P＝0.046] after treatment ，the incidence of myelosuppression [OR ＝0.61，95％CI（0.39，0.97），P＝ 0.035]，fever [OR ＝0.63，95％CI（0.42，0.95），P＝0.027]，nausea and vomiting [OR ＝0.70，95％CI（0.51，0.97），P＝0.030] in trial group were significantly lower than those of control group. There was no statistical significance in the incidence of abdominal pain [OR ＝0.87，95％CI（0.54，1.39），P＝0.547] and skin itching [OR ＝1.63，95％CI（0.36，7.50），P＝0.530] between 2 groups. CONCLUSIONS：Apatinib combined with TACE can significantly improve clinical efficacy ，prolong survival time ，reduce tumor recurrence and metastasis. It can reduce the occurrence of related ADR as diarrhea after TACE ，but increase the occurrence of apatinib-related ADR as myelosuppression.  
          
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      • LI Chunlu,HUANG Feihong,YE Yun,WU Jianming,ZOU Wenjun
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To systematically evaluate efficacy and safety of Shengxuening tablets in the treatment of cancer-related anemia （CRA），and to provide evidence-based reference for clinical drug use. METHODS ：Retrieved from the Cochrane Library ，PubMed，Embase，CJFD，CSJD，Wanfang database and CBM ，RCTs about Shengxuening tablets alone or combined with routine therapy （trial group ）versus routine therapy or blank control （control group ）in the treatment of CRA were collected from inception to July 2019. After literature screening and data extraction ，quality evaluation of included literatures with system evaluation bias risk evaluation tool provided by Cochrane intervention measure system evaluation manual 3.0.2， Meta-analysis of the included literatures was carried out by using Rev Man 5.3 software. RESULTS ：A total of 9 RCTs involving 681 patients were included. Results of Meta-analysis showed that red blood cell count [MD ＝0.62，95％CI（0.30，0.93），P＝0.000 1]， hematocrit level [MD ＝6.12，95％CI（4.97，7.27），P＜0.000 01]，hemoglobin level [MD ＝7.47，95％CI（5.29，9.66），P＜0.000 01]， white blood cell count [MD ＝0.31，95％CI（0.12，0.50），P＝0.001]，platelet count [MD ＝3.06，95％CI（0.84，5.28），P＝0.007]， KPS score [MD ＝5.15，95％CI（2.79，7.51），P＜0.000 1]，quality of life score [MD ＝28.27，95％CI（19.27，37.28），P＜0.000 01] after treatment in trial group were significantly higher than control group ，while the incidence of ADR [RR ＝0.14，95％CI（0.03， 0.76），P＝0.02] in trial group was significantly lower than control group. CONCLUSIONS ：Shengxuening tablets have good efficacy and safety in the treatment of CRA.  
        关键词：Shengxuening tablets;Cancer-related anemia;Meta-analysis;Efficacy;Safety   
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      • XU Peipei,LI Wenrui,ZENG Linan,LIU Dan,ZHANG Yang,MI Xue,HUANG Zongyao,SONG Haoxin,ZHANG Lingli
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To evaluate guidelines f or health technology assessment （HTA）at home and abroad ，and to provide reference for scientific formulation of HTA guidelines in China. METHODS ：Databases including PubMed ，Embase，Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ，including basic characteristics， content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS：A total of 19 guidelines published during 2001 to 2018 were included ，7 guidelines（36.8％）were published in 2015-2020；in addition to 1 guideline from WHO ，14 guidelines （73.7％）were published in Europeand ，2 guidelines（10.5％） in North America and 1 guideline each from South America and Asia （5.3％）. There were 11 guidelines（57.9％）developed by academic organizations and 8 guidelines（42.1％）by health administration ；11 guidelines（57.9％）were evidence-based ，while the others weren ’t evidence- based （42.1％）. The purpose ，content and object of assessment are demonstrated in 19 guidelines；18 guidelines specified the assessment method （94.7％），and 16 guidelines（84.2％）defined the subject of assessment ；14 guidelines （73.7％）specified the HTA assessment process ；12 guidelines（63.3％）mentioned the conflict of interest in HTA assessment process；7 guidelines（36.8％）mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ，but the core contents ar e basically the same. At present ，there is a lack of HTA guidelines in China. We can refer to foreign guidelines，and establish applicable HTA guidelines which aresuitable for national conditions ，so as to provide scientific guidance for HTA research.  
          
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      • QIU Sha,WANG Na,XIANG Jing,QIAN Yan
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To evaluate the efficacy and safety of prophylactic use of low-dose aspirin in patients with chronic renal disease ，and to provide reference for evidence-based reference for rational use in the clinic. METHODS ：Retrieved from PubMed，Embase，Cochrane Library ，CNKI，VIP，Wanfang database ，RCTs about prophylactic use aspirin 75-150 mg/d（aspirin group）versus no aspirin and other antiplatelet drugs or placebo （control group ）were collected from inception to May 14th，2019. Relevant data were extracted. After quality evaluation with bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0，Meta-analysis of the incidence of cardiovascular events ，renal events and bleeding events in patients with chronic renal disease was performed by using Rev Man 5.3 software. RESULTS ：A total of 5 RCTs were included ，involving 4 728 patients；among them ，there were 2 392 persons in aspirin group and 2 390 persons in control group. Results of Meta-analysis showed that there was no statistical significance in the incidence of cardiovascular events [OR ＝0.59，95％CI（0.13，1.12），P＝0.11] and the incidence of renal events [OR ＝0.42，95％CI（0.08，2.23），P＝0.31] between aspirin group and control group. The incidence of bleeding events [OR ＝2.12，95％CI（1.23，3.66），P＝0.007] in aspirin group was significantly higher than control group. After exculsion of two heterogeneity literatures ，the incidence of cardiovascular events [OR ＝0.27，95％CI（0.13，0.55），P＝0.000 3] in aspirin group was significantly lower than control group. CONCLUSIONS ：Prophylactic use of low-dose aspirin can prevent cardiovascular events in patients with chronic renal disease to certain extent. The low-dose aspirin should be used carefully to prevent cardiovascular events in chronic renal disease patients with high risk of bleeding.  
        关键词：Aspirin;Low-dose;Chronic renal disease;Cardiovascular events;Prophylactic use;Meta-analysis   
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      • CHEN Yinqing,WU Weizhe,HE Yanling,HE Fan,CEN Hanjing
        Vol. 31, Issue 12, (2020)
        摘要：OBJECTIVE：To investigate the role of clinical pharmacists on the individualized treatment of children with subglottic Talaromyces marneffei infection. METHODS ：The clinical pharmacists participated in the medication procedure for a case of subglottic T. marneffei infection child . The clinical pharmacists suggested that Budesonide suspension for inhalation should be stopped，according to the subglottic infection pathogen type （T. marneffei ）；Itraconazole oral solution should be chosen and taken orally 2.5 mg/kg，q12 h，and indicators as liver function ，blood potassium should be monitored regularly. However ，as Itraconazole oral solution needed to be applied for temporary purchase ，Itraconazole capsules 2.5 mg/kg，q12 h，p.o.，was administrated temporarily ；clinical pharmacists suggested that Itraconazole capsules should be taken after meal ，and the doctor changed the feeding mode of milk from q 4 h to continuous pumping. After purchased ，Itraconazole oral solution was used instead 2.5 mg/kg，q12 h in fasting state ，and according the clinical pharmacist ’s suggestion ，the doctor changed the nursing method to q 4 h milk pumping. After purchasing and using oral solution instead ，clinical pharmacists suggested taking it at fasting state ；according to the monitoring results and target range （0.5-1 mg/L），oral dose of Itraconazole oral solution was finally adjusted to 8.3 mg/kg， q12 h. In view of the diarrhea during the treatment ，clinical pharmacists suggested to continue the original treatment after considering the effectiveness and importance of the treatment ；at the same time ，discharge medication education should be carried out. RESULTS ： The doctors adopted the suggestions of the clinical pharmacists. The child got a clinical improvement and was discharged after 48 days. CONCLUSIONS ：Clinical pharmacists participate in the treatment of children with T. marneffei infection，timely assist physicians to adjust and improve the medication regimen ，which improve the efficacy and safety of medication for children.  
        关键词：Clinical pharmaci st;Child;Subglottic stenosis;Talaromyces marneffei infection;Pharmaceutical care   
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