最新刊期
卷 32 ， 期 22 ， 2021
- 摘要：OBJECTIVE：To analyze th e risk factors of marketing authorization holder （MAH）pharmacovigilance outsourcing and propose risk management and control strategies ， and to provide reference for MAH to successfully implement pharmacovigilance outsourcing and regulatory authorities to formulate corresponding regulatory strategies. METHODS ：Based on the principal-agent theory and brainstorming method ，the risk factors were preliminarily determined ，and a questionnaire was designed. The questionnaire survey was carried out among pharmacovigilance staff of 200 MAH in Guangdong province by random sampling. The factor analysis method was used to statistically analyze the questionnaire data ，and the comprehensive risk factors and their respective factor scores were summarized. RESULTS & CONCLUSIONS ：A total of 200 questionnaires were distributed ， and 154 valid questionnaires were returned ，with effective recovery rate of 77.00％. The results of factor analysis method showed that there were 4 comprehensive risk factors involved in MAH pharmacovigilance outsourcing activities ，which were service providers and outsourcing management factor （3.792 score），MAH factor （3.766 score），regulations factor （3.626 score）and market factor （3.610 score）from high to low. In view of the above factors ，it is suggested that MAH should focus on improving outsourcing contract ，establishing information communication mechanism with service providers ，strengthening auditing and management，strengthening pharmacovigilance ability and personnel building ，defining appropriate pharmacovigilance outsourcing business contents ， and fully doing pre-service investigation of service providers ， when MAH conducts outsourcing of pharmacovigilance. It is suggested that relevant departments should formulate pharmacovigilance entrusted quality management specifications or guidelines as soon as possible and strengthen the supervision of service providers. It is suggested to try to establish a pharmacovigilance outsourcing industry associa tion， andstandardize the industry behavior by giving full play to the influence of the association ，so as to avoid the outsourcing risk.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To explore th e influential factors of the price fluctuation of Chinese crud drug ，and to provide reference for the healthy development of tranditional Chinese medicine industry in China. METHODS ：Based on the relevant statistics from 1992 to 2019，a structural vector autoregressive model was established. After data stationarity test ，cointegration relationship test ，model estimation and stability test ，impulse response function and variance decomposition were used to investigate the impact of supply ，demand，cost of implantation and production and inflation on the price of Chinese crud drug. RESULTS & CONCLUSIONS：There was a long-term equilibrium relationship among the price of Chinese crud drug ，planting area of Chinese crud drug ，output of Chinese patent medicine ，market turnover of Chinese crud drug ，export volume of Chinese crud drug ，price index of agricultural means of production and consumer price index. The price of Chinese crud drug had the greatest impact and contribution rate on itself ，followed by planting area of Chinese crud drug ，export volume of Chinese crud drug and price index of agricultural means of production. However ，the output of Chinese patent medicine ，the turnover of Chinese crud drug market and consumer price index had weak influence. It is suggested to make full use of Internet information technology ，strengthen the price monitoring and early warning of Chinese crud drug ，promote the supply side structural reform of tranditional Chinese medicine industry，improve the scientific and technological level of Chinese crud drug planting and promote large-scale production of Chinese herbal medicine so as to stabilize the price of Chinese crud drug.关键词：Structural vector autoregressive model;Chinese crud drug;Price fluctuation;Impulse response function;Variance
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish a method for the determination of aloesin in plasma of rats ，and to investigate pharmacokinetic characteristics of aloesin. METHODS ：The plasma samples were precipitated with methanol. Using aloeresin D as internal standard ，the plasma concentration of aloesin was determined by LC-MS/MS. The determination was performed on Synergi Hydro-RP column with mobile phase consisted of 0.1‰ formic acid-methanol （gradient elution ）at the flow rate of 0.50 mL/min. The column temperature was 30 ℃，and sample size was 5 µL. The electrospray ionization source was applied to carry out negative ion detection with multiple reaction monitoring mode . The ion transitions for quantitative analysis were m/z 393.1→272.9（aloesin） and m/z 555.3→144.9（internal standard ），respectively. The concentration of aloesin in venous blood was determined by above method at 0.083，0.167，0.333，0.667，1，1.5，2.5，4，6，8，10 h after intravenous injection （3.35 mg/kg）and intragastric administration（16.75 mg/kg）of aloesin. DAS 3.0 software was used to calculate pharmacokinetic parameters. RESULTS ：The linear range of aloesin were 1-600 ng/mL（r＝0.994 5）. The lower limit of quantification was 1 ng/mL，and RSDs of within and between batches were less than 15％；accuracies within and between batches were within ±15％. The matrix factors were （92.74± 4.33）％-（94.84±2.57）％，and extraction recoveries were （69.04±2.13）％-（75.03±2.84）％；the deviation between the measured results of the stability test and the theoretical values were within ±15％. After intravenous injection and intragastric administration of aloesin ，main pharmacokinetic parameters were as follows ：cmax were（10 693.3±2 745.3）and（223.3±36.2）ng/mL；t1/2 were （2.45±1.45）and（3.33±1.91）h；AUC0－24h were（4 190.6±883.6）and（1 210.1±93.9）ng·h/mL（n＝3）. Absolute bioavailabi- lity was 11.13％. CONCLUSIONS ：The established method is rapid and sensitive for plasma determination of aloesin ，and suitable for its pharmacokinetic study.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To st udy t he effects of total flavonoids from chamomile on lipid metabolism of hyperlipidemia model mice and its potential mechanism. METHODS ：Thirty male C 57BL/6J-ApoE－/－ mice were randomly divided into model group ， positive control group（fenofibrate 30 mg/kg）and chamomile total flavonoids low-dose ，medium-dose and high-dose groups （88， 176，352 mg/kg），with 6 mice in each group. In addition ，6 male C 57BL/6J mice were used as normal control group. Mice in normal control group were fed with ordinary diet ，and mice in other groups were fed with high-fat diet for 8 weeks to replicate hyperlipidemia model. At the time of making model ，administration groups were given relevant liquid （using 1％ sodium carboxymethyl cellulose as solvent ）；normal control group and model group were given 1％ sodium carboxymethyl cellulose intragastrically，200 mL per gavage ，once a day ，for consecutive 8 weeks. The body weight of mice in each group was weighed before medication and 8 weeks after medication. The serum contents of total cholesterol （TC），triacylglycerol（TG），low-density lipoprotein cholesterol （LDL-C），high-density lipoprotein cholesterol （HDL-C），aspartate aminotransferase （AST）and alanine aminotransferase （ALT） in mice were detected after last administration ；the contents of superoxide dismutase （SOD） and malondialdehyde（MDA）as well as the protein expressions of peroxisome proliferator-activated receptor α（PPARα），carnitine palmityl transferase 1A（CPT1A）and peroxase acyl-CoA oxidase 1（ACOX1）in liver tissue were determined. The pathological changes i n liver tissue were observed. RESULTS：Compared w ith before medication ，the body weight of each group showed an increasing trend after 8 weeks of medication. Compared with normal control group ，body weight ，the contents of TC ，TG， LDL-C，AST and ALT in serum and MDA content in live r lan- tissue of mice in model group were significantly increased wei516@sina.com after 8 weeks of medication （P＜0.05 or P＜0.01）. The ·2706· China Pharmacy content of HDL-C in serum and the cont ent of SOD in liver tissue ，as well as the protein expressions of PPARα，CPT1A and ACOX1 were significantly decreased （P＜0.05 or P＜0.01），and the structure of liver tissue was disorganized ，with circular fat vacuoles of different sizes and lipid droplets of different sizes in the cytoplasm. Compared with model group ，body weight （except for chamomile total flavonoids low-dose group ）of mice ，serum contents of TC ，TG，LDL-C，AST and ALT ，content of MDA in liver tissue （except for chamomile total flavonoids low-dose and medium-dose groups ）were significantly decreased （P＜0.05 or P＜ 0.01）. Serum content of HDL-C ，content of SOD in liver tissue ，protein expressions of PPARα，CPT1A（except for chamomile total flavonoids low-dose and medium-dose groups ） and ACOX 1 were significantly increased （P＜0.05 or P＜0.01）；liver tissue structure was clear ，and liver fat vacuoles were improved to varying degrees ，and less lipid droplets. The improvement effect of the above indexes was the best in the chamomile total flavonoids high-dose group. CONCLUSIONS ：Chamomile total flavonoids can prevent the occurrence of hyperlipidemia in C57BL/6J-ApoE －/－ mice，the mechanism of which may be associated with up-regulation of PPARα expression，the improvement of liver injury and oxidant stress injury.关键词：Total flavonoids from chamomile;Hyperlipidemia;C57BL/6J-ApoE－/－ mice;Lipid metabolism;Mechanism of
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish the method for simultaneous determination of 11 active components in Yuhuai tablets ， such as gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside，geniposide，ziyuglycoside Ⅰ ，ziyuglycoside Ⅱ ，narirutin， naringin，hesperidin and neohesperidin. METHODS ：HPLC-QAMS method was adopted. The determination was performed on Agilent TC-C 18column（250 mm×4.6 mm，5 μm）with mobile phase consisted of acetonitrile （A）-0.1％ phosphoric acid solution （B） （gradient elution ）at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelengths were set at 238 nm for gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside and geniposide ，203 nm for ziyuglycoside Ⅰ and ziyuglycoside Ⅱ，and 283 nm for narirutin ，naringin，hesperidin and neohesperidin. Using geniposide as an internal reference ，the relative correction factors of other 10 components relative to this component were calculated ，and the contents of each component in 10 batches of samples were calculated. The results obtained by HPLC-QAMS method were compared with those obtained by external standard method. RESULTS ：The linear ranges of gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside，geniposide， ziyuglycoside Ⅰ，ziyuglycoside Ⅱ，narirutin，naringin，hesperidin and neohesperidin were 0.87-43.50，1.99-99.50，4.06-203.00， 7.35-367.50，12.97-648.50，28.98-1 449.00，3.79-189.50，1.57-78.50，18.05-902.50，0.66-33.00 and 14.38-719.00 μg/mL（all r＞0.999 0）. RSDs of precision ，repeatability and stability （24 h）tests were all less than 2％（n＝6）. The average recoveries were 96.90％-100.10％，and RSDs were 0.67％-1.74％（n＝9）. E-mail：289931673@qq.com There was no significant difference in the contents of 10 active components as gardoside between HPLC -QAMS method and external standard method in 10 batches of Yuhuai tablets （P＞0.05）. CONCLUSIONS ：The HPLC-QMAS method established in this study is convenient and accurate. It can be used for the simultaneous determination of gardoside ，shanzhiside，gardenoside，genipin 1-gentiobioside，geniposide，ziyuglycoside Ⅰ，ziyuglycoside Ⅱ，narirutin，naringin，hesperidin and neohesperidin in Yuhuai tablets.关键词：Yuhuai tablets;HPLC-QAMS;Multi-index component;Relative correction factor;Content
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish a method for the determination of plasma protein binding rate of rosmarinic acid ，caffeic acid and chlorogenic acid from Glechoma longituba . METHODS ：UHPLC method combined with ultrafiltration method was adopted to determine the plasma protein binding rate of rosmarinic acid ，caffeic acid and chlorogenic acid from G. longituba in the plasma of New Zealand rabbits. The determination was performed on a Phenomenex Luna ® C18 column with mobile phase consisted of acetonitrile （A）-0.1％ formic acid solution （B）（gradient elution ）at the flow rate of 0.5 mL/min. The column temperature was set at 45 ℃，and the detection wavelength was 327 nm. The sample size was 3 μL. RESULTS：At low ，medium and high concentrations，the plasma binding rates of rosmarinic acid were （97.78 ± 1.67）％ ，（94.32 ± 1.42）％ ，（95.12 ± 1.51）％ ， respectively（n＝3）；those of caffeic acid were （90.12±2.33）％，（89.53±1.98）％，（90.23±1.56）％，respectively（n＝3）；those of chlorogenic acid were （63.23 ± 2.12）％ ，（67.87 ± 1.06）％ ，（62.34 ± 1.34）％ ，respectively （n＝3）. CONCLUSIONS ： Established method is easy to operate and shorter time for analysis. It can be used to determine the plasma protein binding rate of rosmarinic acid ，caffeic acid and chlorogenic acid in G. longituba .
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish the HPLC fingerprints of Yuebi jiazhu decoction ，determine the contents of ephedrine hydrochloride and pseudoephedrine hydrochloride and carry out chemical pattern recognition analysis. METHODS ：Using ammonium glycyrrhizinate as control ，HPLC fingerprint of 10 batches of Yuebi jiazhu decoction was established and the similarity was evaluated with Similarity Evaluation System for TCM Chromatographic Fingerprint （2012 edition），and common peaks were identified in combination with mixed control. HPLC method was used to determine the contents of ephedrine hydrochloride and pseudoephedrine hydrochloride. SPSS 26.0 software was used for cluster analysis ；SIMCA 13.0 software was used for principal component analysis and partial least squares discriminant analysis ；the differential components affecting the quality were screened. RESULTS：There were 20 common peaks in the fingerprint of Yuebi jiazhu decoction ，and the similarities with control fringerprint were all greater than 0.92. Two peaks were identified ，which were liquiritin （peak 11）and ammonium glycyrrhizate （peak 18）. The linear range of ephedrine hydrochloride and pseudoephedrine hydrochloride were 0.98-48 μg/mL（r＝0.999 9）and 1.02-51 μg/mL （r＝0.999 2），respectively. RSDs of precision ，reproducibility and stability tests （24 h）were all less than 2％. The average recoveries were 105.67％（RSD＝2.88％，n＝9）and 104.15％（RSD＝2.02％，n＝9），respectively. The contents of ephedrine hydrochloride and pseudoephedrine hydrochloride were 0.008 1-0.014 3，0.002 5-0.011 8 mg/mL. Results of cluster analysis showed that among the 10 batches of Yuebi jiazhu decoction ，S1 was clustered into one class ，S3 was clustered into one class ，and S2，S4-S10 were clustered into one class. The results of principal component analysis showed that S 3 was located at the far right side of the scoring plot ，S1 at the right side of the scoring plot ，and S 2，S4-S10 at the middle of the scoring plot. The results of partial least squares discriminant analysis were basically consistent with the results of cluster analysis and principal component analysis. The variable importance projection values of peak 9，peak 3，peak 12，peak 8，peak 19，peak 18 （ammonium glycyrrhizinate），peak 13，peak 20 and peak 11（liquiritin）were greater than 1. CONCLUSIONS ：Established HPLC fingerprint and the method for content determination are simple and accurate. Combined with chemical pattern recognition ，they can be used for the quality control of Yuebi jiazhu decoction. Nine components such as peak 9 are the differential components affecting the quality of Yuebi jiazhu decoction.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To compare the chemical components in Sinapis alba before and after stir-frying. METHODS ： UPLC-Q-Exactive Obitrap MS was adopted to analyze chemical constituents of S. alba before and after stir-frying. The determination was performed on Waters CORTECS T 3 column with mobile phase consisted of methanol- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.25 mL/min. The column temperature was 30 ℃ and the sample size was 2 μL. High resolution MS adopted heating electrospray electron source ，positive ion scanning mode ，scanning range m/z 120-1 000. The chemical constituents of S. alba before and after stir-frying were identified by Compound Discover 3.2 software combined with relevant database ，and the content changes of chemical constituents were analyzed by using peak area. Chemometrics analysis was performed for the content changes of chemical constituents using peak area as variable. RESULTS ：A total of 54 chemical components were identified in S. alba ，mainly fatty acids （represented by erucic acid ），alkaloids（represented by sinapine ）， flavonoids. After stir-frying ，the contents of 19 chemical components changed significantly ，of which the contents of 10 components decreased significantly and those of 9 components increased significantly （P＜0.05）. Principal component analysis and orthogonal partial least squares discriminant analysis could clearly distinguish S. alba from stir-fried S. alba . CONCLUSIONS ：The contents of some chemical components of S. alba change significantly after stir-frying ，which may be one of the important reasons for the change of efficacy after stir-frying.关键词：Sinapis sinapis;Stir-frying;Chemical constituents;UPLC-Q-Exactive Obitrap MS;PCA;OPLS-DA
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To explore t he mechanism of Xinmaikang improving atherosclerosis （AS）in rabbits. METHODS ：A total of 50 male Zealand rabbits were randomly divided into sham operation group ，model group ，simvastatin group [positive control ， 2.60 mg/（kg·d）] and Xinmaikang low-dose and high-dose groups [ 0.21，0.84 g/（kg·d）]，with 10 rabbits in each group. Rabbits in sham operation group were fed with ordinary diet ，and only femoral artery was separated and ligated ，and abdominal aortic endothelium was not strained ；the other groups were given high-fat diet and received abdominal aortic intimal balloon injury to induce AS model. Ten weeks after operation ，sham operation group and model group were given intragastric administration of normal saline ，and administration groups were given corresponding drug solution intragastrically （normal saline as solvent ）with the volume of 100 mL，once a day ，for consecutive 12 weeks. After last administration ，the pathological changes of abdominal aorta and inner wall in rabbits were observed in each group. The serum contents of triglyceride （TG），total cholesterol （TC），low density lipoprotein cholesterol （LDL-C），high density lipoprotein cholesterol （HDL-C），interleukin-6（IL-6）and IL- 1β were detected，and the contents and protein expression of Toll-like receptor 4（TLR4）and nuclear factor-κB p65（NF-κB p65）in abdominal aortic tissue were determined. RESULTS ：Compared with sham operation group ，the intima of abdominal aorta in model group was rich in lipids ，the thickness of vessel wall and plaque area were increased obviously ，and there was obvious vascular endothelial injury. The contents of TG ，TC，LDL-C，IL-6 and IL- 1β in serum，the contents and protein expression of TLR 4 and NF-κB p65 in abdominal aorta tissue were significantly increased ，while the content of HDL-C was decreased significantly （P＜0.05 or P＜ 0.01）. Compared with model group ，the lesion of rabbit abdominal aorta were alleviated ，and no obvious damage was found on the inner wall. The contents of TG ，TC，LDL-C，IL-6，IL-1β of Xinmaikang high-dose group and simvastatin group as well as the content of NF-κB p65 and protein expression of TLR4 and cnd- NF-κB p65 were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：Xinmaikang can improve AS in rabbits ， and its mechanism may be assicated with inhibiting the expression of TLR 4，NF-κB p65 and inhibiting inflammatory response.关键词：Xinmaikang;Atherosclerosis;TLR4/NF-κB signaling pathway;Lipid metabolism;Inflammatory response;Rabbit
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish the method for the content determination of 7 components，such as puerarin ， 3′-methoxypuerarin，daidzein，rutin，hesperidin，salvianolic acid A and quercetin ，in Zhengxin jiangzhi tablets ，and conduct cluster heatmap analysis. METHODS ：HPLC method was adopted. The separation was performed on Kromasil C 18 column with mobile phase consisted of acetonitrile- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.8 mL/min. The detection wavelength was set at 280 nm，and the column temperature was 25 ℃. The sample size was 10 μL. Taking the content data as the object，the cluster heatmap was drawn by Hiplot scientific research mapping platform. RESULTS ：The linear range of puerarin ， 3′-methoxypuerarin，daidzein，rutin，hesperidin，salvianolic acid A and quercetin were 17.00-170.00（r＝0.999 9），5.14-51.40（r＝ 0.999 8），3.00-30.00（r＝0.999 8），153.00-1 530.00（r＝0.999 9），7.88-78.75（r＝0.999 8），2.85-28.50（r＝0.999 9）and 11.34-113.40 μg/mL（r＝0.999 8），respectively. RSDs of precision ，stability（24 h）and repeatability tests were all less than 2％； the average recoveries were 99.58％（RSD＝0.83％，n＝6），100.31％（RSD＝1.17％，n＝6），100.61％（RSD＝1.08％，n＝6）， 100.05％（RSD＝0.82％，n＝6），100.31％（RSD＝1.38％，n＝6），100.31％（RSD＝0.85％，n＝6），99.85％（RSD＝1.01％， n＝6），respectively. The contents of above components in 10 batches of samples were 7.262 5-8.941 5，2.464 9-3.068 9，1.478 9- 1.883 4，58.632 8-79.408 3，3.569 4-4.500 6，1.077 6-1.341 5，1.139 7-5.957 0 mg/g，respectively. Results of cluster heatmap analysis showed that 10 batches of samples could be divided into 4 categories，including S 1-S3 as one category ，S4 as one category，S5-S6 as one category and S 7-S10 as one category. CONCLUSIONS ：The established method is simple ，accurate and specific，which can be used for the quality control of Zhengxin jiangzhi tablets ，combined with cluster heatmap analysis. There are some differences in the quality of different batches of samples.关键词：Zhengxin jiangzhi tablets;HPLC;Content determination;Cluster heatmap analysis
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To investig ate the effects of tenuifolin （TEN）on brain mitochondrial autophagy in Aizheimer ’s disease（AD）model mice. METHODS ：Totally 50 male APP/PS1 double transgenic mice were randomly divided into model group，TEN medium-dose+ 3-MA group [TEN 40 mg/（kg·d）+autophagy inhibitor 3-MA 30 mg/（kg·d）] and TEN low-dose ， medium-dose and high-dose groups [ 20，40，80 mg/（kg·d）]，with 10 mice in each group. In addition ，10 wild-type homologous mice were included in normal control group. Administration groups were intragastrically given corresponding drug solution ；normal control group and model group were intragastrically given 0.3％ sodium carboxymethyl cellulose solution ，once a day ，0.01 mL/g， for consecutive 3 months. After last administration ，positive expression [measured by integrated optical density （IOD）] of microtubule associated protein 1 light chain 3（LC3）in neuron was detected ；mRNA expressions of LC3，ubiquitin-binding protein p62，Cathepsin D ，Rab7，phosphatase and tensin homolog deleted on chromosome ten gene-induced putative kinase 1（PINK1） and E 3 ligase（Parkin）as well as protein expressions of LC 3，p62，PINK1 and Parkin were detected in brain mitochondria. RESULTS：Compared with normal control group ，IOD value of LC 3 in neuron as well as mRNA and protein expressions of LC 3， p62，PINK1 and Parkin in brain mitochondria were all increased significantly in model group （P＜0.05 or P＜0.01），while mRNA expressions of Cathepsin D and Rab 7 were decreased significantly （P＜0.05 or P＜0.01）. Compared wit h model group ，IOD values of LC 3（except for TEN low-dose and medium-dose groups ） in neuron ，mRNA expressions of LC 3，Cathepsin D ，Rab7， PINK1（except for TEN low-dose group ）and Parkin （except for TEN low-dose group ） in brain mitochondria as well as protein expressions of LC 3 （except for TEN medium-dose group），PINK1（except fo r TEN high-dose group decreased significantly）and Parkin （except for TEN low-dose group decreased significantly ）were increased significantly in TEN low-dose ， medium-dose and high-dose groups （P＜0.05 or P＜0.01）；mRNA（except for TEN low-dose group ）and protein expressions of p62 were decreased significantly （P＜0.05 or P＜0.01）. Compared with TEN medium-dose group ，the changes of above indexes were inhibited significantly in TEN medium-dose + 3-MA group （P＜0.05 or P＜0.01）. CONCLUSIONS ：TEN can induce mitophagy in brain tissue of AD model mice by activating PINK 1/Parkin signaling pathway and improve lysosome function.关键词：Tenuifolin;Alzheimer’s disease;PINK1/Parkin signaling pathway;Mitochondrial autophagy;APP/PS1 double
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发布时间：2022-06-21 -
Establishment of HPLC Fingerprint and Content Determination of 5 Components in Papaveris Pericarpium
摘要：OBJECTIVE：To establish the fingerprint of Papaveris Pericarpium， and to determine the contents of 5 components，such as morphine ，codeine，thebaine，papaverine and narcotine. METHODS ：HPLC method was adopted. The determination was performed on a Agilent ZORBAX Eclipse XDB-C18 column with mobile phase consisted methanol -sodium heptanesulfonate with gradient elution at the flow rate of 1.0 mL/min. The detection wavelength were set at 238 nm（papaverine） and 216 nm（morphine，codeine，narcotine，thebaine）. The column temperature was 20 ℃，and sample size was 10 µL. HPLC fingerprints of 15 batches of Papaveris Pericarpium were established by using the Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 edition），and the common peaks were determined in combination with the spectra of mixed control. The contents of morphine ，codeine，thebaine，papaverine and narcotine were determined simultaneously by the same method. The cluster analysis was conducted by using SPSS 19.0 software. RESULTS ：There were 13 common peaks in 15 batches of Papaveris Pericarpium ，and the similarity was greater than 0.99. Five chromatographic peaks were identified ，which were morphine，codeine，thebaine，papaverine and narcotin. The results of cluster analysis showed that 15 batches of Papaveris Pericarpium could be clustered into two categories ，S1-S7 and S 8-S15，belonging to two cities. The linear ranges of five components were 10.21-102.10，10.43-104.30，1.54-30.70，2.36-47.28，2.32-57.90 μg/mL，respectively（all r＞0.998）. RSDs of precision，stability（24 h）and repeatability tests were all less than 2％. The average recoveries were 99.46％（RSD＝1.08％，n＝ 6），97.84％（RSD＝1.55％，n＝6），91.10％（RSD＝1.74％，n＝6），96.43％（RSD＝1.25％，n＝6）、94.82％（RSD＝1.20％，n＝6）， respectively. The contents of 5 components were 2.342 9-4.082 2，0.430 4-0.889 7，0.055 2-0.090 4，0.299 3-0.558 8，0.343 2- 0.656 2 mg/g. CONCLUSIONS ：The established HPLC fingerprint and content determination method is simple ，feasible，sensitive and accurate. It combined with the cluster analysis could reflect characteristics and int ernal quality of chemical components in Papaveris Pericarpium . Papaveris Pericarpium in different cities possess regionalization characteristics ，but its quality isbasically stable.- 71
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To evaluate the econo mics of pembrolizumab in the second-line treatment of advanced hepatocellular carcinoma in China. METHODS ：From the perspective of Chinese healthcare system ，a three-state PartSA model and Markov model were established ；the cost and utility for the second-line treatment of advanced hepatocellular carcinoma in China were compared between pembrolizumab and placebo. The circulation cycle of the model was 3 weeks and the study time limit was lifetime；one-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS ：PartSA results showed that the ICER for the second-line treatment of advanced hepato- cellular carcinoma with pembrolizumab was 1 266 846.18 yuan/QALY，which is far more than 1-3 times of China ’s per capita GDP in 2020. The results of one-way sensitivity analysis showed that the three parameters that had the greatest impact on ICER were the PFS status utility of the placebo group ，the PFS status utility of the pembrolizumab group ，and the cost of pembrolizumab. The results of probability sensitivity analysis verified the robustness of the base-case analysis. The scenario analysis showed that the treatment cost of pembrolizumab had dropped significantly when the charity donation of pembrolizumab was considered. Although it was still not economical ，ICER was close to 3 times of per capita GDP of China in 2020. When WTP threshold was 1 and 3 times of China ’s per capita GDP ，the economic prices of pabolizumab （100 mg）were 4 157.67 and 5 829.24 yuan，respectively. The results of Markov model were similar to those of PartSA model. CONCLUSIONS ：Under the WTP threshold of 1-3 times China ’s per capita GDP in 2020，pembrolizumab is not economical for second-line treatment of advanced hepatocellular carcinoma.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.关键词：Pyrrotinib;LC-MS/MS;Imatinib;Breast cancer;Plasma concentration monitoring
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To observe the efficacy and safet y of roxadustat in the treatment of chronic kidney disease （CKD） combined with renal anemia. METHODS ：The data of 80 inpatients with CKD combined with renal anemia treated in the nephrology department of the First Affiliated Hospital of Anhui University of Science and Technology during Nov. 2019 to Dec. 2020 were analyzed retrospectively. They were divided into observation group （40 case）and control group （40 case）according to different treatment methods. Control group was given Human erythropoieti n for injection subcutaneously ，100-150 IU/kg every week，3 times a week. Observation group were given Roxadu- stat capsules orally ，100 mg each time for dialysis patients with a bodyweight of 45-＜60 kg，70 mg each time for non- 717060193@qq.com dialysis patients ，3 times a week ；120 mg each time for dialysis patients with bodyweight ≥60 kg and 100 mg each time for non-dialysis patients ，3 times a week. After 4 weeks of treatment ，the dosage of the two groups w as adjusted according to the level of hemoglobin （Hb）. Treatment course of 2 groups were 12 weeks. The levels of anemia indexes （Hb，red blood cell count （RBC），hematocrit（Hct）），iron metabolism indexes （serum iron （Fe），ferritin（Fer），total iron-binding capacity （TIBC），tranfeerrin saturation （TSAT）），lipid metabolism indexes （total cholesterol （TC），triglycerides（TG），high-density lipoprotein （HDL），low-density lipoprotein （LDL））and inflammation index（C-reactive protein （CRP））were detected in 2 groups before treatment and after 12 weeks of treatment. The levels of Hb were observed in high-level CRP subgroup and low-level CRP subgroup ；the occurrence of ADR was recorded in 2 groups during treatment. RESULTS ：Before treatment ，there was no statistical significance in the anemia indexes ，iron metabolism indexes ，lipid metabolism indexes or inflammation index between 2 groups（P＞0.05）. After treatment ，the levels of Hb ，RBC and Hct in 2 groups and the levels of TIBC and HDL in observation group were significantly higher than before treatment. The levels of Fe ，Fer and TSAT in 2 groups and the levels of TC and LDL in observation group were significantly lower than before treatment ；the levels of Hb ，RBC，Hct，TIBC and HDL in observation group were significantly higher than before control group ，while the level of TC was significantly lower than control group （P＜0.05）. The incidence of high reactivity in observation group was significantly higher than control group ，while the incidence of low reactivity was significantly lower than control group （P＜0.05）. There was no statistical significance in the levels of CRP between 2 groups before and after treatment （P＞0.05）. Subgroup comparison results showed that there was no statistical significance in the level of Hb between high-level CRP subgroup and low-level CRP subgroup of 2 groups before treatment （P＞0.05）. After treatment ，the level of Hb in high-level CRP subgroup of observation group was significantly higher than that of high-level CRP subgroup of control group （P＜0.05）. The total incidence of ADR in observation group was significantly lower than control group （P＜0.05），and no severe ADR was observed in 2 groups. CONCLUSIONS ： Roxadustat can effectively improve anemia in CKD patients with renal anemia ，and curative effect is less affected by inflammatory state，and it has good short-term safety.关键词：Roxadustat;Chronic kidn ey disease;Renal anemia;Efficacy;Safety;Inflammation state
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To systematically e valuate the efficacy and safety of expectorant/antioxidants in the treatment of chronic obstructive pulmonary disease （COPD），and to provide evidence-based reference for clinical use. METHODS ：Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，CBM，CNKI，VIP，Wanfang database ，etc.，randomized controlled trials（RCTs）about expectorant/antioxidants （trial group ）versus placebo （control group ）in the treatment of COPD were collected during the inception to May 2021. After literature screening and data extraction ，the quality of included literatures were evaluated with risk bias evaluation tool recommended by Cochrane systematic evaluator manual 5.1.0. The consistency check was performed by using Gemtc 14.3 software；network Meta-analysis ，clustering and hierarchical sorting were performed with Stata 15.1 software. The publication bias was analyzed by inverted funnel plot. RESULTS ：A total of 12 RCTs，involving 4 637 patients，were included. Five interventions measures were involved ，such as low-dose N-acetylcysteine （NAC），high-dose NAC ，carbo- cisteine， erdosteine and placebo. The results of network Meta-analysis showed that in terms of annual acute aggrava- tion rate ，the patients receiving high-do se NAC [MD ＝－0.45， 163.com 95％CI（－0.74，－0.17），P＜0.05]，carbocisteine [MD ＝－0.59，95％CI（－0.86，－0.32），P＜0.05] and erdosteine [MD ＝－0.26，95％CI（－0.51，－0.01），P＜0.05] in trial group were significantly lower than those in control group ；the annual acute aggravation rate of patients receiving high-dose NAC[MD ＝－0.55， 95％CI（－0.98，－0.11），P＜0.05] and carbocisteine [MD ＝－0.69，95％CI（－1.11，－0.26），P＜0.05] in trial group were significantly lower than those receiving low-dose of NAC ，there was no statistical significance among other groups （P＞0.05）； probability cumulative ranking results （calculated by the area under the curve ）of its network Meta-analysis was carbocisteine ＞ high-dose NAC ＞erdosteine＞placebo＞low-dose NAC. In terms of the incidence of ADR ，there was no statistical significance among groups （P＞0.05）；probability cumulative ranking results （calculated by the area under the curve ） of its network Meta-analysis was erdosteine ＞high-dose NAC ＞low-dose NAC ＞placebo＞carbocisteine. The results of clustering and hierarchical ranking showed that the efficacy and safety of the five interventions could be grouped into three categories ，including placebo and low-dose NAC with low efficacy and safety ，carbocisteine with good efficacy but low safety ，and high-dose NAC and erdosteine with good efficacy and safety. The results of publication bias showed that taking the annual acute exacerbation rate as the index ， there was a greater possibility of publication bias in this study ；taking the incidence of adverse event as index ，there was little possibility of publication bias in this study. CONCLUSIONS ：NAC，carbocisteine and erdosteine all can reduce the annual acute aggravation rate and have low incidence of ADR. Carbocisteine is the best in terms of annual acute aggravation rate ，erdosteine is the best in terms of safety. High-dose NAC and erdosteine are both better in term of efficacy and safety.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To explore the role of clinical pharmacists in the diagnosis and tre atment of immune checkpoint inhibitor related adrenocortical insufficiency ，so as to provide reference for the diagnosis and treatment of similar cases. METHODS：A lung squamous carcinoma patient with tumor immunotherapy ，who received long-term intravenous infusion of Pembrolizumab injection ，was hospitalized for more than 10 days due to fatigue and poor appetite. The clinical pharmacists consulted the literature and evaluated the correlation of ADR on the basis of patient ’s physical examination results （plasma cortisol 16.41 nmol/L at 8：00 in the morning on the second day of admission ，adrenocorticotropic hormone 8.39 pg/mL，serum electrolyte sodium 126.00 mmol/L，chlorine 88.00 mmol/L，etc.）and medication history （receiving the treatment with immune checkpoint inhibitors）. The clinical pharmacists assisted the doctor to confirm that the patient was adrenocortical insufficiency ，and the correlation with pembrolizumab was “very likely ”. On the basis of discontinuation of pembrolizumab ，it was recommended to take Hydrocortisone tablets orally （20 mg at 8：00 in the morning and 10 mg at 4：00 in the afternoon ）for glucocorticoid physiological dose substitution therapy. Before treatment ，the patient and his families should be educated on the use of drugs ，pharmaceutical care should be implemented to evaluate the glucocorticoid doseand efficacy during treatment ，and medication education was carried out at discharge. RESULTS ：The doctor adopted theli_xyan suggestions of the clinical pharmacist. On the 5th day after @126.com administration，the symptoms of adrenocortical insufficiency were significantly impro ved，and the patient was discharged with medicine. CONCLUSIONS ：During the treatment of the patient ， the clinical pharmacist gave full play to his pharmaceutical expertise ，assisted the doctor to formulate an appropriate medication plan，and carried out medication education for the patient and his family members ，so as to ensure the effectiveness and safety of the patient ’s medication. It is suggested that the baseline examination of patients should be improved before immune checkpoint inhibitor treatment ，including physical examination and plasma cortisol level at 8：00 in the morning ；the frequency of monitoring plasma cortisol level and serum electrolyte level at 8：00 in the morning. should be increased during medication ；the patients should be followed up for at least 1 year after withdrawal ，so as to early detect and treat immune checkpoint inhibitor related adrenocortical dysfunction.关键词：Pembrolizumab;Adrenocortical insufficiency;Immune-related adverse events;Pharmaceutical care;Clinical
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To pr ovide reference for the development of pharmacoeconomic budget impact analysis and related decision-making. METHODS ：Taking the incremental number of people using new intervention measures as the starting point ，a new algorithm was designed ，and the advantages and potential application scope of the new algorithm were compared with those of common algorithms. RESULTS & CONCLUSIONS ：The new algorithm directly used the sales data from the real world to calculate the number of users and their increment of each intervention scheme. Compared with common algorithms ，the new algorithm did not consider the unchanged part of the number of users of each intervention scheme ，but focused on the changing part of the number of users ，avoided the estimation of the number of the target population and the users of some intervention schemes ，and could solve the problem of unreasonable or inaccurate prediction of the target population and market share by common algorithms to a certain extent ；moreover，it could be flexibly adjusted to adapt to different market conditions and medical insurance access conditions. However ，due to the strong subjectivity of key parameters （such as preemption rate ）or inaccurate data sources ，the calculation results of the new algorithm are still uncertain.关键词：Budget impact anal ysis;Increment of users;Algorithm;Pharmacoeconomics;Preemption rate
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发布时间：2022-06-21
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