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  • Orginal Article
    Wei LI, Chengliang ZHANG, Dong LIU
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    The preparation of Calculus bovis and its compounding preparations have been used widely in clinical practice. Traditionally, the forms of medicine were in raw material medicine way, preparing tablet, pill,powder or directly taking its powder. The main active ingredient of Calculus bovi were considered to be bilirubin and bile acids.However, the traditional formulations caused low bioavailability and wasted expensive herbs because its main component were insoluble in water. In recent years,many researchers have tried to use modern preparation technology to prepare its compounding formulations, such as solid dispersion technology, ultrafine grinding technology, powder coating technology, liposome encapsulation technology, or simplifying the prescription by using of known pharmacological effects of soluble components as substitutes. These methods were considered to be feasible to develop new formulations of Calculus bovis.In this paper,in order to provide reference of method and technology for the improvement of Calculus bovis compounding preparation and the development of new dosage form,ultramicrostructure, chemical composition,improvement methods and techniques of compounding preparation were analyzed. In addition, the relevant techniques and method of improving the formulation Calculus bovis compounding preparation in recent years were reviewed.

  • Orginal Article
    Zhenhong HU
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    The choice of initial anti-infection empirical therapy is the key to the successful treatment of community-acquired pneumonia in adults. This review is aimed at interpretation of the 2016 edition of Guidelines for the Initial Anti-infection Empiric Therapy Management of Chinese Adult Patients with Community-Acquired Pneumonia based on the different characteristics of antimicrobial agents. It may be useful for clinical physicians and pharmacists understand and master the guidance theoretically and practically, and also help them to select the empirical anti-infection treatment of adult patients with community-acquired pneumonia in combining regional epidemiological characteristics reasonably.

  • Orginal Article
    Guoqiang LIU, Shengnan GAO, Yingying ZHENG
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    This study is aimed to make a comprehensive introduction to the anti-MRSA drugs, and also to compare the safety and efficacy among a variety of anti-MRSA drugs. Finally, it is pointed that we should select the anti-MRSA drugs precisely according to different situation of disease when treating the infection with MRSA.Then we can make the individualized treatment for patients and provide a basis for the disease when treatment of patients as well.

  • Orginal Article
    Mingfang YANG, Xiaohua CHENG, Wenwei XU
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    Objective To explore the absorption characteristics and mechanism of P-glycoprotein (P-gp) mediated transport of oleanolicacid (OA)across membrane in vitro.Methods The intake and transport of OA were evaluated by an HPLC/MS quantitative detection method.Safe concentration range of OA was determined by MTT.The effect of different drug concentration, incubation time, pH and temperature on the intake of OA by Caco-2 cells were investigated.The effect of P-gp inhibitor on the transmembrane transport of OA was investigated by the Caco-2 cell monolayer model, and the apparent permeability coefficient (Papp) was calculated. Results The uptake of OA was concentration-time dependent and correlated negatively to temperaturein Caco-2 cells within the safe concentration range, but was not significantly affected by pH value.Compared with controls, the Pappsignificantly changed when the P-gp inhibitor was added to the model(P<0.05).The apparent permeability ratio decreased from 2.90 to 0.95.Conclusion The absorption of OA was primarily by passive diffusion and might be mediated by the efflux by P-gp.

  • Orginal Article
    Yingcong YANG, Kang LIU, Fang ZHOU, Qingtao MENG, Zhongyuan XIA
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    Objective To establish neuropathic pain models, explore the effects and mechanisms of dexmedetomidine on neuropathic pain. Methods Wistar rats were randomly divided into four groups (n=9): 0.9% sodium chloride solution CCI group (N),dexmedetomidine CCI group (D), ZD7288 CCI group (Z) and sham-operated group (Sham). Sciatic nerve ligation was performed in group N, D and Z. The sciatic nerve in group Sham was exposured without ligation. 7 d after surgery, the rats in group D were intraperitoneal injected with dexmedetomidine (40 μg·kg-1), and the rats in group Z were intraperitoneal injected with ZD7288 (10 mg·kg-1)once a day for 3 d.The same volume of 0.9% sodium chloride solution was given at the same time in group N. The behavioral test was performed before and 7 d after operation, as well as 3 d after injection treatment. Mechanical allodynia was assessed by paw withdrawal mechanical threshold (PWMT) to von Frey filaments. Thermal hyperalgesia was assessed by paw thermal withdrawal latency (TWL) to radiant heat. Dexmedetomidine block of HCN channels in dorsal root ganglion (DRG) neurons were confirmed by whole-cell recording. Results 7 d after surgery, the PWMT and TWL of rats in group N, D and Z were decreased significantly (P<0.05). The PWMT and TWL in group Sham were no significant difference before and after operation. Dexmedetomidine significantly increased the levers of PWMT and TWL in group D and Z after treatment for 3 d,and group Z was greater than group D (P<0.05). Dexmedetomidine(0.1,1, 10 μmol·L-1)caused a concentration-dependent decrease in the amplitude of Ih in DRG neurons from (-844.43±386.34)to(-215.99±63.90) pA(P<0.05), and the inhibition rate of Ih was(11.87±1.80)%,(35.26±3.65) % and (52.02±5.56)%, respectively(P<0.05). Dexmedetomidine produced a dose-related shift to the left of the Ih activation, and a negative shift in V1/2 (P<0.05). V1/2 shifted from (-86.21±1.68)to (-103.54±2.01)mV(P<0.05). The slope values were not altered by dexmedetomidine.Conclusion Dexmedetomidine produces a dose-dependently analgesic effect on neuropathic pain after peripheral never injury, which is likely due to the inhibition of Ih and reduction of ectopic spontaneous discharge in DRG neurons.

  • Orginal Article
    Jun LIANG, Lili GAO, Yinan WANG, Xiaobo YANG, Guozhu HAN
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    Objective To investigate effects of diabetes mellitus(DM) on pharmacokinetics (PK) of cephradine (CED). Methods DM model was induced by iv.alloxan 60 mg·kg-1. A reversed phase HPLC internal standard method was developed for measurement of CED plasma concentration. After blood collection, rats were sacrificed to collect kidneys for calculating kidney index(KW/BW). DM and normal control (CTL) rats were randomly assigned to receive iv.or ig. CED at a dose of 180 or 90 mg·kg-1. The 3p97 program was used to calculate PK parameters. Results The developed HPLC method was validated to have high specificity, precision, recovery and good storage stability, and met requirements for PK study of CED. The CED in rats of both DM and CTL groups showed the iv.two-compartment PK and ig.one-compartment PK and followed the first-order kinetics. Following iv. dosing, a remarkably decreased t1/2β and MRT,increased CLtwere evident in DM group as compared with CTL group (P<0.05). After ig dosing, a significant decrease in t1/2k and tmax, a remarkable increase in CLt and Cmax were observed for DM group as compared with CTL group (P<0.05). The DM rats showed a trend of decreased t1/2kavs CTL rats. There was no significant difference in the oral bioavailability between the two groups (P>0.05). KW and KW/BW in DM group were increased remarkably compared with CTL group (P<0.05).Conclusion The DM vs CTL results in faster absorption and elimination of CED in rats, but does not have significantly affect in oral bioavailability. The compensatory hypertrophy and hyperfunction of early-stage diabetic kidneys may constitute one of causes of quick elimination of CED in rats with DM.

  • Orginal Article
    Jiping HUO, Shenghui MEI, Zhigang ZHAO, Hongyun WANG, Pei HU, Pingya LI, Jinping LIU, Ji JIANG
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    Objective To evaluate the uncertainty of the pseudo-ginsenoside GQ (PGQ) concentration in human plasma by HPLC-MS/MS. Methods The whole process of PGQ determination by HPLC-MS/MS in human plasma was evaluated and the uncertainty caused by repeatability, weighing, standard solution preparation, biological sample preparation, extraction recovery process, recovery, instrument precision and calibration curve fitting were evaluated, respectively. The combined and expanded uncertainty values were both calculated. Results The expanded uncertainty values for low (15.16 ng·mL-1), medium (2 516.67 ng·mL-1) and high (3 902.00 ng·mL-1) levels of PGQ were 1.39, 177.74 and 262.69 ng·mL-1, respectively (P=95%, k=2).Conclusion The uncertainty of the PGQ determination in human plasma by HPLC-MS/MS is mainly caused by recovery, repeatability and sample preparation at low concentration, by sample preparation and recovery at medium and high concentration.

  • Orginal Article
    Changjiu GAO, Chaoli ZHANG, Zhujia ZHENG, Jiafu HOU, Huan LIU, Ting WU, Huiying BI, Guangping WANG, Jindan AN, Zhongcheng YU
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    Objective To study the anti-inflammatory, antitussive, and analgesia effects of Jinhua qingre capsules. Methods The anti-inflammatory effect was assessed by the methods include xylene-induced mouse auricular swelling and histamine-induced pigment oozing from skin vessel in rats; The antitussive and analgesic effect were assessed by ammonia water induced cough model and acetic acid-induced twisting method. Results In anti-inflammation experiment, the high dose (12 g·kg-1) and moderate (6 g·kg-1) groups of Jinhua qingre capsules showed significant inhibitory effect on auricular swelling and significant difference compared with control group (P<0.01, P<0.05); the high dose (10 g·kg-1) and moderate dose (5 g·kg-1) groups of Jinhua Qingre capsules play a marked inhibitory role in the increase in mouse peritoneal capillary permeability (P<0.01, P<0.05). In antitussive experiment, high dose (12 g·kg-1) and moderate dose (6 g·kg-1) groups had significant inhibitory effect on cough caused by ammonia water (P<0.01, P<0.05) compared with control group. In analgesic experiment, the high dose (12 g·kg-1), moderate dose (6 g·kg-1), and low dose (3 g·kg-1) groups effectively reduced the writhing frequency of mice (P<0.01, P<0.05).Conclusion Jinhua qingre capsules have potential effects on anti-inflammatory, antitussive, and analgesic.

  • Orginal Article
    Biao XU, Kun ZENG, Xiangping MENG
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    Objective To study the protective effect of nalmefene hydrochloride on lung ischemia-reperfusion injury and its mechanism. Methods 40 rats were randomly divided into model group, high dose of nalmefene group, low dose nalmefene group and sham operation group equally(n=10). The lung ischemia-reperfusion model was established by occlusion of the left pulmonary hilum. The intravenous injection of nalmefene (20,10 μg·kg-1) was applied at 10 minutes before occlusion of the left pulmonary hilum in the high dose of nalmefene group and the low dose of nalmefene group, respectively. The sham operation group without occlusion of the left pulmonary hilum was not given any treatment. At 2 h after reperfusion, all rats were detected arterial blood gas value and then sacrificed. The specimens from the upper lobe of the left lung tissue were preserved to observe pulmonary lesions, detect the ratio of wet / dry weight and the expressions of β-endorphin and interleukin(IL)-17. Results Compared with the model group, the value of PCO2, the degree of pulmonary lesions, the ratio of wet / dry weight and the expressions of β-endorphin and IL-17 in lung tissue were significantly decreased (P<0.01), while the value of PO2 was significantly increased (P<0.01) in the low dose of nalmefene group. Compared with the low dose of nalmefene group, the value of PCO2, the degree of pulmonary lesions, the ratio of wet/dry weight and the expressions of β-endorphin and IL-17 in lung tissue were significantly decreased (P<0.01), while the value of PO2 was significantly increased (P<0.01) in the high dose of nalmefene group.Conclusion Nalmefene hydrochloride may prevent lung ischemia-reperfusion injury in a dose dependent manner by reducing the production of β-endorphin and inhibiting the expression of IL-17 in lung tissue.

  • Orginal Article
    Jiajia JIANG, Jing FENG, Rong DAI, Yuan YANG, Yi LIANG, Yang WANG, Fan ZHANG
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    Objective To systematically review the effectiveness and safety of statins for chronic obstructive pulmonary diseases (COPD) combining with pulmonary hypertension (PH). Methods The electronic searches in databases of PubMed, EMbase, the Cochrane Library, Web of Science, CBM, CNKI, VIP and Wanfang Data were conducted from the date of their establishment to January 2016 and the references of the include studies were also retrieved for collecting randomized controlled trials (RCTs) or quasi-RCTs on statins treating COPD combining with PH. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, assessed the quality of the included studies by adopting the Cochrane collaboration’s tool for assessing risk of bias, and performed Meta-analysis by using RevMan 5.3 software. Results A total of 24 studies involving 1 587 cases were included. The results of Meta-analysis showed that: compared with the control group, simvastatin significantly improved FEV1 [MD=0.23, 95%CI: 0.16-0.31,P<0.000 01], FEV1% [MD=6.73, 95%CI: 1.34-12.12,P=0.01], FVC [MD=0.39, 95%CI: 0.34-0.45,P<0.000 01], 6 minutes walk distance (6MWD) [MD=59.09,95%CI: 54.24-63.93,P<0.000 01] and decreased mPAP [MD=6.73, 95%CI: 1.34-12.12,P=0.01], SPAP [MD=-4.53,95%CI=-8.87--0.19,P=0.04]. Atorvastatin significantly improved FEV1 [MD=6.22, 95%CI: 2.51-9.93,P=0.001] and 6MWD [MD=24.10, 95%CI: 12.98-35.23,P<0.000 1] and decreased sPAP [MD=-6.44, 95%CI: -7.95--4.93,P<0.000 01] and mPAP [MD=-3.51,95%CI: -5.81--1.22,P=0.003]. But no significant difference was found in the improvement of FEV1,FVC or FEV1/FVC. Fluvastatin significantly decreased sPAP [MD=-5.89, 95%CI: -6.99--4.79,P<0.000 01]. There was a significant decrease in the Borg dyspnoea score in statins group [MD=-3.37, 95%CI: -4.61--2.14,P<0.000 01] as compared with the controls. In addition, the incidence of adverse drug reactions (ADRs) was similar between statins and the control group.Conclusion Current evidence suggests that statins may decrease pulmonary hypertension in patients with COPD combining with PH. However, high-quality clinical trials with large sample size are needed to verify whether the improvement of pulmonary function, 6MWD and Borg dyspnoea score are the class effect or the incidence of ADRs is disparate among different statins.

  • Orginal Article
    Guangyi YANG, Chenning ZHANG, Rongjiao ZHANG, Jinbao WEI, Weidong MA, Yonghong ZHANG
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    The enterohepatic circulation is an important form of drug absorption and excretion. Drugs with enterohepatic circulation can induce toxic side effects, and elucidate the mechanism of induced side effects is a necessary understanding of the phenomenon of adverse drug reaction. Enterohepatic circulation of drugs involves in two ways: one is based on the drug prototype for enterohepatic circulation; the other is phase Ⅱ metabolic pathway for enterohepatic circulation. In this paper, two kinds of enterohepatic circulation were reviewed. The toxic side effects of six kinds of drugs with enterohepatic circulation were introduced, and the possible mechanism were described and discussed, so as to have contributed to more rational use of drugs in clinical practice. Furthermore, it can promote the research and development of new drugs.

  • Orginal Article
    Peilei LI, Meng GUO, Wenyuan GUO
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    Initially, the renin-angiotensin system (RAS) was considered to play an important role in regulating cardiovascular function and maintaining the balance of water and electrolyte. Based on this, several targeted drugs in the treatment of hypertension were developed. With the large-scale clinical application of these drugs, RAS inhibitors are found to has a significant inhibitory effect on some of the tumor development, which reveals the RAS function in cell proliferation, differentiation, angiogenesis and tumor occurrence. In this paper, the important physiological function of RAS in tumor occurrence and development were reviewed.

  • Orginal Article
    Dong XIANG, Zhiyong YANG, Jianwu HE, Chunyang SHI, Jianguo FANG, Wenqing WANG
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    Objective To establish HPLC determination method and impurity profile of the related substances in metronidazole. Methods A Welch Ultimate?XB-C18(4.6 mm×250 mm, 5 μm)was used with a mobile phase consisting of methanol-1.36 g·L-1 solution of potassium dihydrogen phosphate (20∶80). The detection wavelength was 315 nm and the flow rate was 1 mL·min-1. Its related substances were determined by principal component self-contrast method. Results Good separation of metronidazole and the impurities could be achieved. Twenty batches of samples in the past six years were determined which meet quality standards. The study of impurity profiles could effectively monitor the synthetic process and the change of impurities in metronidazole.Conclusion The method is simple, quick and sensitive, which can be used to control the related substances in metronidazole. Meanwhile, the impurity profiles ensure the quality stability of metronidazole.

  • Orginal Article
    Wan LEI, Yuxia KANG, Ying WANG, Feiyan GUO, Ting ZHOU, Xiaojuan WANG
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    Objective To establish the quality standard for qingkou granules and qingkou sugarless granules. Methods Puerarin, Acteoside, Mori Folium, Lycii Fructus, Oleanolic Acid and Glycyrrhizae Radix et Rhizoma were identified by TLC. The content of puerariae was detected by HPLC. The determination was performed on Diamonsil C18(2)(250 mm×4.6 mm,5 μm) column with mobile phase consisted of methanol-water (25∶75); The detection wavelength was set at 250 nm. Results TLC spots of them could be detected clearly and were specific without interference from negative control. The linear range of puerperia was 18.00—144.02 μg·mL (r=0.999 8, n=8). The average recovery of qingkou granules and qingkou sugarless granules were 101.02% (RSD=1.66%, n=9), and 98.83% (RSD=1.46%, n=9), respectively.Conclusion The method is simple,accurate,specific,reproducible,and can be used for quality control of qingkou granules and qingkou sugarless granules.

  • Orginal Article
    Jianmou LIANG, Cong FU, Yue CHEN
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    Objective To establish a LC-MS analytical method for determination of N,N-dimethylaniline which is genotoxic impurity in quetiapine fumarate. Methods The method was achieved by an Waters ACQUITY UPLC CSHTM Phenyl-Hexyl(2.1 mm×100 mm,1.7 μm) utilizing a mobile phase of buffer-methanol(900∶100)(A)-acetonitrile(B) with gradient elution at the flow rate of 0.4 mL·min-1. The temperature of column was set at 50 ℃; The DIONEX Ultimate 3000 HPLC-AB Science 4000 QTrap Tripling Four bar LC-MS to detect N,N-Dimethylaniline (ESI source, in MRM positive mode). Results Standard curve was linear in the range of 0.4—8.0 ng(r=0.999 3); The limit of detection was 0.2 ng; The limit of quantification of N,N-dimethylaniline was 0.4 ng,respectively. The average recovery of N,N-dimethylaniline was 103.3%; RSD was 4.3% (n=9), respectively.Conclusion The method is convenient and sensitive for the determination of N,N-dimethylaniline in quetiapine fumarate.

  • Orginal Article
    Qiaoyuan CHENG, Cheng ZHENG, Yuqian ZHENG, Bilian CHEN
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    Objective To establish the quality standard of Xiao'er resuqing granules. Methods Rhei Radix et Rhizoma, Bupleuri Radix, Forsythiae Fructus, Puerariae Lobatae Radix in the granules were qualitatively identified by the method of thin layer chromatography (TLC). The content of baicalin was analyzed by the method of high performance liquid chromatography (HPLC). Results There were good specificities of the TLC method to identify Rhei Radix et Rhizoma, Bupleuri Radix, Forsythiae Fructus, Puerariae Lobatae Radix. The linear range of baicalin was 0.116 2—1.743 0 μg (r=1.000 0). The average of recovery and RSD were 100.61%, 0.79% (n=6), respectively.Conclusion The method established in this study is simple, accurate, reliable and suitable to be applied to quality control for the preparation of Xiaoer resuqing granules.

  • Orginal Article
    Bing SHU, Tianlu SHI, Shengyu ZHANG, Yancai SUN, Yan SUN, Wei WEI, Ling JIANG
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    Objective To explore possible impact factors through investigating and analyzing the occurrence of potentially inappropriate medications (PIMs) in elderly inpatients. Methods Clinical pharmacists evaluated 365 drug prescriptions for elderly inpatients older than or equal to 65-year-old from January to June of 2014 based on Beers criteria published in 2012,aimed at determining incidence and impact factors of potentially inappropriate medications as well as analyzing potentially drug interactions and service condition of traditional Chinese medicine injections that were not included in Beers criteria. Results A total of 189 subjects (51.78%) used no less than one potentially inappropriate medications. Seventy four subjects (20.27%) used drugs with potential drug interactions. Two hundred and seventy three patients (74.79%) used troditional Chinese Medicine Injections. The impact factors on potentially inappropriate medications in elderly inpatients included combined use of drugs,hospitalization days,age and Charlson Comorbidity Index scores. Taking PIMs was significantly positively correlated with the occurrence of potential drug interactions and service condition of traditional Chinese medicine injections.Conclusion According to characteristics of epidemiology and clinical medication use in the hospital or region, clinical pharmacists should refer to Beers criteria so as to pay attention to clinical complications of elderly inpatients. Moreover, clinical pharmacists should emphasize drug interactions and remind physicians and inpatients using traditional Chinese medicine injections cautiously,aimed at decreasing drug risks of elderly inpatients, and promoting reasonable drug use in elderly inpatients.