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China Pharmacy

1990  to  Present  ISSN: 1001-0408

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Investigation and Analysis of the Current Operation Situation o f Online Drugstores in China

Xueyan ZHANG ; Jun YAN ; Ping WANG ; Suzhen WANG

China Pharmacy.2019;30(2):145-149.

OBJECTIVE: To investigate the current situation and existing problems of online drugstores in China and put forward corresponding countermeasures and suggestions, so as to provide a basis for promoting and improving the standardization of online drugstores in China. METHODS: The number of online drugstores was counted by inquiring about the online drugstores in all provinces, autonomous regions and municipalities directly under the central government published by the “Public inquiry” column on the official website of the previous China Food and Drug Administration (CFDA). According to the administrative division, stratified sampling of online drugstores was conducted. The website domain names of sampled online drugstores and their Taobao stores, Jingdong stores, Wechat public accounts, Wechat small programs and other platforms were retrieved to analyze their operation methods. At the same time, the online drugstores which actually had online trading behavior were investigated and analyzed from three aspects, including business scope, propaganda behavior and service behavior. RESULTS & CONCLUSIONS: A total of 693 online drugstores were obtained from the official website of CFDA, and the domain names of only 14 (41.2%) of 34 online drugstores selected by stratified sampling were their corresponding online drugstores. Other online drugstores had some problems, such as domain name could not be opened or was not related websites. There were 14 online drugstores dealing in drugs through their own websites, of which 12 also operated on third-party platforms such as Taobao, Jingdong and Wechat. The problems of 27 drugstores with online online trading behavior mainly included non-standard operating varieties, illegal sale of prescription drugs, disunity of qualification mark,false propaganda,untimely online customer service response and imperfect drug distribution system, etc. It is suggested that relevant supervisory and administrative departments strengthen supervision, standardize the management of domain names and trading platforms of online drugstores, and vigorously crack down on and control illegal online transactions. Online drugstores should improve their service levels, standardize their own website construction, improve the level of real-time customer service and drug distribution services, so as to improve the current operation situation of online drugstores in China.

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Problems of Clinical Use in Pediatric Drug and Countermeasures Analysis in China

Xueyun WANG ; Weiwei SU ; Hong DING ; Wen GUO ; Xuewei HUA

China Pharmacy.2019;30(2):149-153.

OBJECTIVE: Te analyze the problems of clinical use in pediatric drug in China, and to put forward related countermeasures and suggestions. METHODS: Using “children” and “pediatrics” as retrieval words, registered drug information were retrieved from the website of China Food and Drug Administration; the data of pediatric drug use prescription was retrieved from hospital prescription system of 9 hospitals; all drug information were retrieved from national drug data management system; off-label drug use investigation and the literatures of pediatric drug use in medical institutions (5 representative third grade general medical institutions) were retrieved from CNKI and Wanfang database. General information and problems of pediatric drug use in China were investigated. RESULTS: A total of 170 009 items of registered drug information were retrieved, including 2 784 drug information items labeled with ”children” or ”pediatrics”, accounting for 1.64%;320 000 drug prescriptions from hospital prescription system of 9 hospitals covered 22 treatment areas involving 1 186 drugs and 51 dosage forms. Only 10% suitable for children. The retrieval results of database showed that the incidence of children off-label drug use in outpatients prescriptions of 5 hospitals was in high level, mainly manifesting as without the information of pediatric drug use, hyper-indication drug use, hyper-dosage drug use. There were many problems in clinical pediatric drug use in China, such as less variety for children, single dosage form and specification, widespread off-label drug use, lack of scientific reference for drug use, difficulty in developing pediatric drug clinical trials, etc. CONCLUSIONS: Although the policies to protect children’s clinical drug use have been introduced in China, the problems facing children’s clinical drug use in China are still very serious. While further implementing relevant policies, it is necessary to establish a linkage management system led by government departments, with the full participation and mutual cooperation of society, enterprises, medical institutions and patients so as to guaratee the safety of pediatric drug use in clinic.

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Establishment of Rational Drug Use Evaluation Model Based on 360-degree Feedback Evaluation Method and Hesitant Fuzzy Sets Theory

Wenjie WANG ; Yuying LIU ; Zhe HUANG

China Pharmacy.2019;30(2):154-159.

OBJECTIVE: To establish a comprehensive and multi-angle evaluation model for rational drug use in medical institutions, and to provide support for rational drug use in medical institutions. METHODS: Referring to the phenomenon of irrational drug use and its influential factors in medical institutions, rational drug use evaluation indicator system, which contained 3 evaluation subjects, 6 first-level indicators and 15 second-level indicators, was established on the basis of 360-degree Feedback Method, with hospitals at the same level, superior regulation department and patient as subjects of multi-angle evaluation. At the same time, the linguistic information of vague and uncertain evaluation given by the evaluation subject was comprehensively quantified by Hesitant Fuzzy Sets Theory. The total evaluation score of rational drug use in the evaluated medical institutions was calculated by using the score function formula of hesitant fuzzy number; the level of rational drug use in medical institutions was determined according to the score (the higher the total score, the higher the comprehensive level of rational drug use). RESULTS: An all-round and multi-angle evaluation model of rational drug use in medical institutions was established. According to the evaluation index system based on 360-degree feedback evaluation method, the evaluation subject and weight of evaluation index were determined, the grade of evaluation index was divided, the hesitant fuzzy numbers of each index were gathered, and the first-level index was weighted. Finally, the total evaluation score of rational drug use in medical institutions was calculated; the examples were set to prove the feasibility of the model. CONCLUSIONS: The established evaluation model for rational drug use in medical institutions based on 360-degree Feedback Method and Hesitant Fuzzy Sets Theory can comprehensively and effectively evaluate the rational drug use in medical institutions, and contribute to standardizing and improving clinical drug use behavior in medical institutions.

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Visualization Analysis of Domestic Drug Centralized Procurement Study from 2000 to Jun. 2018

Bilin SONG ; Jiao YUAN ; Lin YE

China Pharmacy.2019;30(2):160-164.

OBJECTIVE: To explore the situation and research hotspots of drug centralized procurement study, and to find existing problems in the development of this field so as to provide reference for further improving drug centralized procurement in China. METHODS: The literatures were retrieved from CNKI, Wanfang and VIP database during 2000-Jun. 2018. CiteSpace software, which was a visualization software, was used to analyze statistically the publication time, author, research institution and keywords. RESULTS: A total of 3 455 literatures were included in the study. The number of literatures in this field had increased significantly since 2009. The author and institution cooperation network were scattered relatively. The research teams were mainly universities and research institutes, few of which were public hospitals. Before 2009,the scholars focused on feasibility analysis of the implementation of drug centralized procurement policy in China, analysis of centralized drug procurement system and model introduction. After New Medical Reform in 2009, great importance was attached to effect evaluation of essential medicine centralized procurement and rational drug use in public hospital. In recent year, the latest outbreak of the keywords were “drug pricing reform”“price negotiation”“medical insurance payment”“drug shortage”“tripartite linkage of medical institutions”“drug purchasing with quantity”“supply guarantee” and so on, which were the newest research hotspots.  CONCLUSIONS: The research focus of drug centralized procurement is changing with the adjustment of national policy. At present, the focus of research in this field has shifted to the research on the mode and situation of drug purchasing with quantity, the reform of medical insurance payment standard, the negotiation of drug price in public hospitals and the reform of drug price. Under the background of “Tripartite Linkage of Medical Institutions”, the strategy of drug supply guarantee system was improved, and the countermeasures are explored to alleviate drug shortage and irrational drug use. In the future, cooperation and academic exchanges should be strengthened in this field so as to make the multi-center and multi-disciplinary cooperation mode should become the mainstream. At the same time, public hospitals should enhance their main position and actively participate in research on related topics, so as to promote to establish and improve the drug supply guarantee system and reduce the medical burden of the public.

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Investigation on Anti-atherosclerosis Mechanism of Tiaopi Huxin Prescription Based on Cav- 1/NF-κB Pathway

Tong LIN ; Chushuo SHI ; Zhizhong SUN ; Shuliang JI ; Junmao WEN ; Qianying CHEN ; Weipeng SUN ; Tian ZHANG ; Xiaoqi ZHOU ; Junzhe LI

China Pharmacy.2019;30(2):165-169.

OBJECTIVE: To study the effects of Tiaopi huxin prescription (TPHXP) on the atherosclerosis (AS) of ApoE-/- mice, and to investigate its mechanism. METHODS: Forty male ApoE-/- mice were divided into blank group, model group, simvastatin group (positive control, 5 mg/kg) and TPHXP low-dose and high-dose groups (50, 150 mg/kg), with 8 mice in each group. Except that blank group was given common diet, other groups were given high-lipid diet to induce AS model. After modeling, administration groups were given relevant medicine intragastrically, and blank group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 12 weeks. After last medication, the serum levels of TC, TG, LDL-C and HDL-C were determined by spectrophotometry. The serum level of NO was detected by nitrate reduction method. The serum levels of IL-6 and VCAM-1 were determined by ELISA. After separating thoracic aorta, HE staining was used to observe the formation of plaque in the thoracic aorta of mice in each group, and the corrected plaque area was calculated. Western blotting was conducted to determine the expression of NF-κB p65, Cav-1 and eNOS. RESULTS: Compared with blank group, the serum levels of TC, TG, LDL-C, IL-6 and VCAM-1 were increased significantly in model group, while the levels of HDL-C and NO were decreased significantly (P<0.01). The plaque of thoracic aorta was obvious and the corrected plaque area were increased significantly (P<0.01). The relative expression of NF-κB p65 and Cav-1 were increased significantly, while the relative expression of eNOS was decreased significantly (P<0.01). Compared with model group, the serum levels of TC, TG and LDL-C in administration groups, the serum levels of IL-6 and VCAM-1 in simvastatin group and TPHXP high-dose group were decreased significantly, while the serum levels of HDL-C and NO were increased significantly in administration groups (P<0.05 or P<0.01). In administration groups, the plaques of thoracic aorta were reduced and the corrected plaque area was decreased significantly (P<0.05 or P<0.01); the relative expression of NF-κB p65 and Cav-1 were decreased significantly, while the relative expression of eNOS was increased significantly (P<0.05 or P<0.01). CONCLUSIONS: TPHXP can regulate the level of blood lipid, decrease the level of inflammatory factors and inhibit the formation of AS plaque, the mechanism of which may be associated with inhibiting Cav-1/NF-κB pathway.

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Study on the Metabolic Characteristics of Piperitylmagnolol in Different Species of Liver Microsomes by UPLC-MS/MS

Xing DENG ; Liya LUO ; Liping GOU ; Qianwen WEN ; Minghai TANG ; Li WAN

China Pharmacy.2019;30(2):170-175.

OBJECTIVE: To establish a method for the determination of piperitylmagnolol in the incubation system of liver microsomes, and to investigate the metabolic characteristics of it in different species of liver microsomes. METHODS: The piperitylmagnolol were respectively dissolved in NADPH activated liver microsome incubation systems of human, rat, mouse, monkey and dog, and then incubated in water at 37 ℃. The reaction was terminated with methanol at 0, 2, 5, 10, 15, 20, 30, 45 and 60 minutes of incubation, respectively. Using magnolol as internal standard, UPLC-MS/MS method was used to determine the concentration of piperitylmagnolol in the incubation system. The determination was performed on Acquity UPLCTM CSH C18 column with mobile phase consisted of 0.1% formic acid-methanol (gradient elution) at the flow rate of 0.3 mL/min. The column temperature was set at 30 ℃, and the sample size was 2 μL. The ion source was electrospray ion source, and the positive ion scanning was carried out in the multiple reaction monitoring mode. The ion pairs used for quantitative analysis were m/z 401.2→331.1 (piperitylmagnolol) and m/z 265.1→247.0 (internal standard), respectively. Using the concentration of piperitylmagnolol at 0 min of incubation as a reference, the residual percentage, metabolism half-life in vitro (t1/2) and intrinsic clearance (CLint) were calculated for different incubation systems. The metabolic pathway of piperitylmagnolol was studied by chemical inhibitor method. Under the above chromatographic conditions, the metabolites in vitro were preliminarily analyzed by first-order full scanning and positive ion detection. RESULTS: The linear range of piperitylmagnolol was 3.91-500.00 ng/mL. The limit of quantitation was 3.91 ng/mL. RSDs of intra-day and inter-day were less than 10%. The accuracy ranged 87.40%-103.75%. Matrix effect didn’t affect the determination of the substance to be measured. The piperitylmagnolol was metabolized significantly in human, rat, mouse and dog liver microsomes, but not in monkey liver microsomes. After incubating for 30 min, residual percentage of piperitylmagnolol kept stable in different species of liver microsomes. The t1/2 of piperitylmagnolol were 12.07, 17.68, 17.59, 216.56 and 61.88 min in human, rat, mouse, monkey and dog liver microsomes; CLint were 0.115, 0.078, 0.079, 0.006, 0.022 mL/(min·mg), respectively. Inhibitory rates of CYP2A6, CYP2D6, CYP2C19, CYP3A4, CYP2C9, CYP2E1 and CYP1A2 to compound metabolism were 55.76%, 93.94%, 96.01%, 93.69%, 71.81%, 23.25%, 28.04%, respectively. Quasi-molecular ion peaks of the two main metabolites of piperitylmagnolol in human liver microsomes were m/z 441.2([M+Na]+) and m/z 337.2([M+H]+), respectively. CONCLUSIONS: Established UPLC-MS/MS method is simple, rapid and specific, and can be used for the determination of piperitylmagnolol concentration in the incubation system of liver microsomes and pharmacokinetic study. The metabolic characteristics of the compound are different among liver microsomes of human, rat, mouse, monkey and dog. Its metabolism process may be associated with CYP2D6, CYP2C19, CYP3A4, CYP2C9, etc.

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Establishment of Elimination Method of Outliers Based on Grubbs Rule and MATLAB Language and Its Application in Ev- aluating Drug Bitterness

Ruixin LIU ; Yanli WANG ; Yao ZHANG ; Xinjing GUI ; Junming WANG ; Qingxiao WANG ; Jing YAO ; Lu ZHANG ; Junhan SHI ; Xuelin LI

China Pharmacy.2019;30(2):176-182.

OBJECTIVE: To establish the elimination method of outliers based on Grubbs rule and MATLAB language, and to evaluate the effects of it on drug bitterness evaluation. METHODS: Referring to Grubbs rule, the automatic cyclic outliers elimination method based on MATLAB language was established. Totally 20 volunteers were included in single oral taste test (Tetrapanax papyrifer) and multiple oral taste test (10 kinds of medicinal material as T. papyrifer, Changium smyrnioides, Poria cocos, etc.). Seven sensors were selected for electronic tongue test (Clematis armandii). The data of bitterness evaluation in above tests (oral taste test as bitterness value, electronic tongue test as response value of sensors) were used as the data source. Five researchers were selected and adopted table-by-table elimination method based on Grubbs rule (method one), Excel software elimination method based on Grubbs rule (method two) and automatic cyclic outliers elimination method based on Grubbs rule and MATLAB language (method three) to judge and eliminate the outliers. The effects of above three methods were evaluated with the removal time and error rate of outliers as indexes. RESULTS: There were two outliers in the data of bitterness evaluation in single oral taste test; the elimination time of the three methods were(745.400 0±25.904 4),(288.333 3±31.253 1)and(0.000 3±0.000 0)s, respectively; error rates were 20.0%, 0 and 0, respectively. There were six outliers in the data of bitterness evaluation in multiple oral taste test; the elimination time of three methods were (3 693.107 7±75.023 3), (1 494.761 4±53.826 9), (0.005 2±0.000 0)s, respectively; error rates were 10.0%, 4.0%, 0, respectively. There were three outliers in the data of bitterness evaluation in electronic tongue test; the elimination time of three methods were (2 992.673 3±84.117 6), (1 276.367 1±55.024 5), (0.002 3±0.000 0)s, respectively; error rates were 5.7%, 2.9%, 0, respectively. The elimination results of the three methods were consistent. The elimination time of method two was significantly shorter than that of method one (P<0.01); the elimination time of method three was significantly shorter than those of method one and method two (P<0.01). There was no significant difference in error rate of 3 methods (P>0.05). CONCLUSIONS: The automatic cyclic elimination method of outliers based on Grubbs rule and MATLAB language can significantly shorten the elimination time of outliers in data of drug bitterness evaluation, improve the efficiency of data processing, and is suitable for drug bitterness evaluation.

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Improvement Effects of Bee Venom Plastics on Experimental Cerebral Thrombosis in Rats

Miao HE ; Zhixue ZHANG ; Hairong ZHAO ; Xiumei WU ; Yu ZHAO ; Chenggui ZHANG

China Pharmacy.2019;30(2):182-187.

OBJECTIVE: To study the improvement effects of Bee venom(BV) plastics on experimental cerebral thrombosis in rats. METHODS: Totally 96 SD rats were randomly divided into sham operation group (normal saline), model group (plastics blank matrix), Nimodipine group (positive drug, 4.00 mg/kg) and BV plastics low-dose, medium-dose, high-dose groups (1.67, 3.33, 6.67 mg/kg), with 16 rats in each group. Rats in sham operation group and Nimodipine group were given medicine intragastrically, while rats in model group and BV plastics groups were given medicine by transdermal smearing. After 5 days of continuous administration, the experimental cerebral thrombosis model was established by ligating the right external carotid artery and pterygomandibular artery, and injecting compound thrombus inducer into the internal carotid artery. The wet mass ratio of right brain to left brain was measured to investigate the degree of brain edema on the infarcted side. The content of Evans blue (EB) in the left and right hemispheres of rats was determined by ultraviolet spectrophotometry to investigate the cerebral vascular permeability. Blood rheology and coagulation function indicators of rats were measured. The pathological changes of brain tissue in rats were observed by HE staining, and the number of survival neuron cells was counted. RESULTS: Compared with the indexes of sham operation group, the cerebral thrombosis model was established successfully. Compared with model group, the area of blue staining in the right brain (infarcted side) of rats in BV plastics groups was significantly reduced, and the right brain/left brain wet mass ratio and the content of EB in the right brain tissue were significantly reduced (P<0.05 or P<0.01). The whole blood viscosity and Casson viscosity of rats in BV plastics groups, and the plasma viscosity of rats in BV plastics medium-dose and high-dose groups decreased significantly (P<0.01). PT and APTT of rats were prolonged significantly in BV plastics medium-dose group (P<0.01). The pathological changes of brain tissue in rats in BV plastics groups were significantly alleviated. The arrangement of neuron cells was more orderly, the shape and structure of cells were clear, the nucleolus was clear, the membrane was intact, and the number of survival neuron cells was significantly increased (P<0.01). CONCLUSIONS: BV plastics can alleviate brain edema, inhibit cerebral vascular permeability, improve hemorheology and coagulation function indicators of rats after the formation of cerebral thrombosis, and alleviate nerve cell injury after ischemia.

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Establishment of HPLC Fingerprint and Principal Component Analysis of Xiaojin Capsules

Kaili MING ; Yang XIANG ; Yanxia YANG ; Tian ZENG ; Yatou WANG ; Wei CAI ; Wen ZHU

China Pharmacy.2019;30(2):188-192.

OBJECTIVE: To establish HPLC fingerprint of Xiaojin capsules, and to conduct principal component analysis. METHODS: HPLC method was adopted. The determination was performed on Agilent TC-C18(2) column with mobile phase consisted of acetonitrile-0.2% formic acid solution (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was 240 nm, and column temperature was 25 ℃. The sample size was 20 μL. Acetyl-11-keto-β-boswellic acid was used as reference and HPLC fingerprints of 15 batches of Xiaojin capsules were determined. The similarity evaluation of common peaks was conducted by using the TCM Chromatographic Fingerprint Similarity Evaluation System (2004A edition) to confirm common peaks. Principal component analysis was conducted by using Minitab 17.0 software. RESULTS: The similarity of 1 batch of sample was lower than 0.800; there was no common peaks No. 13, 14, 15 in HPLC chromatogram of the batch, compared with other 14 batches. There were 15 common peaks in the HPLC fingerprints of 14 batches of samples and three chromatographic peaks were identified, such as quercetin,amentoflavone, acetyl-11-keto-β-boswellic acid. The similarity of 14 batches ranged 0.889-0.990. Through principal component analysis, accumulative contribution rate of 2 principal component factors was 94.4%. It was indicated that the content change of corresponding components of common peaks No. 8, 9, 11, 12, 14 in samples was an important reason for the quality difference of samples, especially common peaks No.8, 9. CONCLUSIONS: The established HPLC fingerprint and principal component analysis can provide reference for quality evaluation of Xiaojin capsules.

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Optimization of Extraction Technology of Volatile Oil and Inclusion Technology in Quhan Zhufeng Granules

Zhirui ZHANG ; Xixiang LI ; Shenghua LI ; Jiwen LI ; Yingyan BI ; Xuemei WANG

China Pharmacy.2019;30(2):192-196.

OBJECTIVE: To establish the method for content determination of ligustilide and to optimize the extraction technology of volatile oil and inclusion technology in Quhan zhufeng granules. METHODS: HPLC method was adopted. The determination was performed on Waters C18 column with mobile phase consisted of methanol-water (70 ∶ 30, V/V) at the flow rate of 1 mL/min. The detection wavelength was set at 327 nm, and the column temperature was 30 ℃. The sample size was 10 μL. Using yield of volatile oil and the content of ligustilide as index, with soaking time, the amount of adding water and extraction time as factors, the extraction technology was optimized by orthogonal test. Using inclusion rate, the yield of inclusion compound and yield of volatile oil as index, with ratio of volatile oil to β-cyclodextrin, inclusion temperature and inclusion time as factors, the inclusion technology of volatile oil was optimized by orthogonal test. RESULTS: The linear range of ligustilide was 0.4-4 μg(r=0.999 9); RSDs of precision, stability and reproducibility tests were all lower than 2% (n=6). The recoveries were 96.75%-102.03%(RSD=2.06%,n=6). The optimal extraction technology of volatile oil included 10-fold water (mL/g), soaking for 15 min, extracting for 8 h. Average yield of volatile oil was 0.310 7%, and average content of ligustilide was 0.418 0 mg/g. The optimal inclusion technology of volatile oil included ratio of β-cyclodextrin and volatile oil was 1 ∶ 8 (mL/g); inclusion temperature was 50 ℃; inclusion time was 3 h. Average inclusion rate was 69.43%, and the yield of inclusion compound was 58.89%; the yield of volatile oil was 14.15%. CONCLUSIONS: Established determination method is simple, accurate and stable. The optimal extraction technology of volatile oil and inclusion technology are stable and feasible.

Country

China

Publisher

中国医院协会;重庆大学附属肿瘤医院

ElectronicLinks

http://www.china-pharmacy.com

Editor-in-chief

E-mail

info@china-pharmacy.com

Abbreviation

China Pharmacy

Vernacular Journal Title

中国药房

ISSN

1001-0408

EISSN

Year Approved

2007

Current Indexing Status

Currently Indexed

Start Year

1990

Description

历史沿革【现用刊名:中国药房;创刊时间:1990】,该刊被以下数据库收录【CA 化学文摘(美)(2009);Pж(AJ) 文摘杂志(俄)(2009)】,核心期刊【中文核心期刊(2008);中文核心期刊(2004)】,期刊荣誉【中科双效期刊;第三届(2005)国家期刊奖获奖期刊】。

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