In recent years, the widespread of resistant bacteria and the slow progress of new antibiotics are posing a serious threat to clinical antibacterial treatment.Combination therapy has become a popular strategy due to this thorny problem.The efficacy of combination therapy is mainly evaluated by in vitro trials, and the data of clinical trials are very limited.Therefore, this paper reviews the indications, interactions and regimens of antibiotics combination, in order to provide theoretical basis for clinical rational drug use.
Objective To explore the reproductive risk of antihypertensive drugs in men of childbearing age. Methods PubMed, Web of Science, EMbase, Scopus, Chinese National Knowledge Infrastructure (CNKI), VIP Information and Wanfang Data were used as data sources.The studies on male reproductive risk of antihypertensive drugs published until December 2017 were collected by search strategy, and supplemented by manual retrieval of important references. Results The analysis showed that β receptor blockers and diuretics were related to the occurrence of male sexual dysfunction, however, angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers had little effect, or even a positive impact on male sexual function.Captopril and enalapril can improve sperm quality parameters and are recommended for use in hypertensive patients of child bearing age.The β-blockers, diuretics and calcium channel blockers have some negative effects on sperm quality in vitro and in animal experiments, but there is a lack of further clinical research. Conclusion Currently, there are few studies focused on reproductive risk of antihypertensive drugs, and most of them are based on animal or in vitro studies.It is still a problem need to further confirm by long-term and large-scale clinical studies.When male patients of childbearing age using antihypertensive drugs, it is recommended that doctors or pharmacists fully inform patients of the reproductive risks of different antihypertensive drugs, dispel patients' concerns, and prevent patients from stopping drugs on their own because of the reproductive risks.At the same time, drug factors should be taken into account when reproductive problems occur during these medications use.
Objective Preparation and characterization of metformin hydrochloride, metformin nitrate and metformin phosphate were performed. Methods The three kinds of metformin salts were analyzed using infrared spectroscopy (IR), Raman spectroscopy (RM), differential scanning calorimetry, thermogravimetry and powder X-ray diffraction. Results The three metformin salts have similar absorption peaks in the IR and RM spectra as well as their own characteristic absorption peaks.They have respective endothermic peak, exothermic peak and mass loss phenomenon in the differential scanning calorimetry and thermogravimetry.Their topological patterns of powder X-ray diffraction patterns also show obvious differences. Conclusion IR and RM can provide comprehensive structural information of three metformin salt.Differential scanning calorimetry and thermogravimetry can give thermodynamic information when sample was heated.Combined with powder X-ray diffraction, more data for the analysis of the structure can be obtained.
Objective To observe the effects of the mercury-containing and mercury-free preparations of Tibetan medicine Shiwuweiyunpeng powder on acute gouty arthritis (AGA) rats. Methods Seventy male SD rats were randomly divided into 7 groups (10 rats in each group): blank control group, model control group, colchicine tablet group, Shiwuweiyunpeng powder group with high or low dose of mercury preparation, and mercury-free preparation group with high or low dose.AGA model was prepared in other groups except blank control group and model control group.The large and small dose groups were given Shiwuweiyunpeng powder 0.28 and 0.07 g·kg-1 respectively by gavage.The colchicine tablets group was given 0.6 mg·kg-1 by gavage.The blank control group and the model control group were given corresponding volume of purified water.All models were made and the drug was administered at the same time for 5 consecutive days.The swelling degree of the ankle joint was measured by measuring scale.Serum interleukin 1β (IL-1β), prostaglandin E2 (PGE2) and tumor necrosis factor α (TNF-α) were measured by ELISA. Results Compared with the model control group, the degree of foot and ankle swelling in each dose group of Shiwuweiyunpeng powder containing mercury preparation and mercury-free preparation was significantly reduced (P<0.05) 24 to 48 h after modeling.Compared with the model control group, the serum levels of IL-1β and PGE2 in rats in the large and small dose groups of Shiwuweiyunpeng powder containing mercury were significantly decreased (P<0.05 or P<0.01), mercury-free high-dose group had a significantly lower serum PGE2, the difference was statistically significant (P<0.05). Conclusion Both the mercury-containing and mercury-free preparations of Shiwuweiyunpeng powder could reduce the ankle swelling and inflammatory factors caused by sodium urate in AGA rats, and the mercury-containing preparations could significantly reduce the effects of IL-1β and PGE2 compared with the mercury-free preparations.
Objective To investigate the effect and mechanism of histone lysine demethylase KDM4A(JMJD2A)in the regulation of hepatocellular carcinoma(HCC) cell proliferation. Methods The lentiviral particles, including Lenti-shKDM4A#1, Lenti-shKDM4A#2,Lenti-shctr,Lenti-HA-Myr-AKT and Lenti-HA-vector, were packaged in 293T cells.The KDM4A knockdown model and control cells were established in Hep3B cell line.Colony formation assay was used to observe the cell proliferation in shKDM4A and control cells.AKT activation was detected by Western Blot.The Myr-AKT was stably over-expressed in KDM4A knockdown cells, then the cell growth condition was observed to confirm the role of KDM4A in cell proliferation depending on AKT activation. Results Two KDM4A knockdown cell lines, shKDM4A#1 (P<0.01) and shKDM4A#2 (P<0.001), formed significantly less clones than the control group.The phosphorylation level of AKT dramatically decreased after KDM4A knockdown,and AKT downstream signal protein P-GSK-3b (ser9) expression level reduced correspondingly.Furthermore,overexpression of Myr-AKT in shKDM4A Hep3B cells could reverse the effect of KDM4A on cell proliferation. Conclusion KDM4A regulates the HCC cell proliferation depending on AKT activation.
Objective To investigate the protective effect and mechanism of chlorogenic acid on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) of mice. Methods Fifty mice were randomly divided into 5 different groups (10 in each group): control group, LPS group, and 3 groups of LPS+CGA in different doses (5, 10 and 20 mg·kg-1).The control group received intraperitoneal injection of PBS 20 mL·kg-1; LPS group received intraperitoneal injection of LPS solution 10 mg·kg-1; and LPS+CGA group received LPS as above and intraperitoneal injection of CGA in 0.9% sodium chloride solution.After 24 hours, the blood and kidney tissues of the mice were collected for histopathological examination and biochemical assays to determine the changes of serum creatinine (Scr), urea nitrogen (BUN), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-1β and TLR4/NF-κB signaling pathway. Results Chlorogenic acid inhibited LPS-induced renal histopathological changes, serum BUN and creatinine levels in a dose-dependent manner, the differences were statistically significant (P<0.05,P<0.01) compared with the LPS group.Chlorogenic acid can suppress LPS-induced TNF-α, IL-6 and IL-1β levels (P<0.05,P<0.01).In addition, chlorogenic acid can significantly inhibit LPS-induced phosphorylation of NF-κB p65 and TLR4 signaling (P<0.05,P<0.01). Conclusion Chlorogenic acid can ameliorate LPS-induced acute kidney injury in mice by regulating TLR4/NF-κB signaling to exert its anti-inflammatory effects.
Objective To provide opinions about choosing Reference Listed Drug (RLD) by analysis of originator drugs manufactured in China. Methods We clarified the definition and scope of originator drugs manufactured in China,and introduced the policies and guidelines of National Medical Products Administration.Then, the current state was analyzed from basic information,registration state,in-vivo evaluation process and original products in US/EU. Results To figure out the percentage of RLD in each categories. Conclusion There are advantages for choosing originator drugs manufactured in China as RLD, but more attention should be paid on relevant influence factors in application processes of consistency evaluation.
Biochemical injection is a kind of high risk drugs for its biological diversity and composition uncertainty.The current paper elaborated the evaluation strategies according to the status quo and technical regulations of the domestic biochemical injections.Key points of the quality evaluation and expectation of the technical methods were investigated and summarized.This paper aims to provide research ideas for quality consistency evaluation or reevaluation work of biochemical injection in the future.
This paper investigates the application and approval of bioequivalence (BE) waiver in the consistency evaluation of generic drugs so far, and analyzes the problems existing in the study and applications.It focuses on the types, dosage, influencing methods and principles of excipients affecting the absorption of drugs, to give reference to enterprises and drug regulatory departments.
Consistency evaluation of generic drugs is the key to substitute generic drugs for expensive branded original drugs.In recent years, a series of policies have been issued to encourage consistency evaluation of generic drugs.The evaluation method has developed from in vitro dissolution evaluation to comprehensive pharmacokinetic and bioequivalence evaluation, and generic drugs must be evaluated in accordance with the designated reference preparations in order to avoid error propagation in the process of copying.Gradually, the methods of consistency evaluation are becoming more scientific and standardized.With the approval of consistency evaluation, generic drugs can replace the original drugs in clinical practice and improve their recognition in medical staff and patients.It is an effective approach to save medical expenses, improve the quality of generic drugs, promote the overall development level of the pharmaceutical industry in China, and ensure the safety and effectiveness of drug used by the public.
Objective To compare the fine particle characteristics of salbutamol sulfate metered dose inhalers from two manufacturers, a mathematical model was built to explore the method of correspondence evaluation for drug. Methods The fine particle characteristics of salbutamol sulfate metered dose inhalers from two manufacturers were determined by Anderson cascade impactor (ACI) and HPLC, respectively.Aerodynamic assessment of fine particles was determined by means of fine particle fraction (FPF), mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD).The aerodynamic particle distribution function was also established. Results Inhalers from manufacturer A had less fine particle fraction and higher mass median aerodynamic diameter, geometric standard deviation was basically higher than inhalers from manufacturer B.The fitting degree of the fine particle distribution function of manufacturer A was better than that of manufacturer B. Conclusion The aerodynamic particle distribution functions which two manufacturers are different could be a effective means of consistency evaluation for inhalation preparation.
Objective To evaluate the tolerability and safety of single and multiple subcutaneous administration of exenatide in Chinese healthy volunteers. Methods This study carried out a tolerability study after single- and multiple-dose subcutaneous administration of exenatide.A randomized single center clinical trial was performed with preprandial subcutaneous administration.In the single-dose group, twenty-four healthy volunteers were randomly divided into two groups: 5 μg (n=12) and 10 μg (n=12), respectively.After the single-dose test, subjects were given multiple doses: twice daily, for consecutive 5 days.The safety profiles and tolerability were evaluated inⅠphase drug clinical trial ward by observing the symptoms, vital sign, electrocardiograms (ECGs), and laboratory parameters (including blood and urine routine, blood glucose, liver and kidney function) before and after subcutaneous administration.At the same time, the adverse drug reactions (ADRs) were recorded. Results There were no significant changes in vital signs and ECGs and laboratory tests that showed no organic injury before and after single and multiple subcutaneous administration.In the single-dose of 10 μg exenatide and multiple-dose of 5 and 10 μg exenatide, there occurred ADRs in 3, 1 and 11 cases, respectively.The most common ADRs of exenatide for injection were mild gastrointestinal symptoms (e.g., nausea, vomiting, and loss of appetite), which were relieved and disappeared without treatment. Conclusion Subcutaneous administration of exenatide is safe and well tolerated in healthy Chinese volunteers with a single- and multiple-dose of 5 and 10 μg exenatide.However individual differences and possible ADRs should be closely monitored in clinical application.
Objective Comparing the dissolution curves and bioequivalences of the imported reference naproxen tablets and generic drugs, to evaluate their consistency and give some reasonable suggestions for their formulations and manufacturing. Methods The dissolution curves of the reference listed drug (RLD) produced by Japanese Tanabe Mitsubishi Corporation and the generic drugs produced by 8 pharmaceutical enterprises were determined in five dissolution mediums: hydrochloric acid solution (pH 1.2), acetate buffer (pH 5.5), phosphoric acid salt buffer (pH 6.0), phosphoric acid salt buffer (pH 6.8) and water.The dissolution curves of consistency were evaluated by the f2 similarity factor method.In the meantime, the in vitro-in vivo correlation models were established using GastroPlusTM combined with in vitro dissolution data to evaluate the bioequivalence of the RLD and the generic drugs. Results The dissolution curves between generics and RLD were dissimilar (f2<50).There was significant difference between the simulated parameters of generic drugs and the previous reported in vivo values. Conclusion The dissolution behaviors of generic drugs and RLD are dissimilar,which indicates that the formulations and manurfacturing technology of generic drugs should be optimized.And GastroPlusTM software can be used to predict the bioequivalence of the generic drugs and RLD.
Objective To evaluate the efficacy and safety of biapenem in the treatment of chronic liver disease complicated with acute bacterial infection. Methods A retrospective multicenter open-label cohort study was conducted in 820 patients.Each patient was given biapenem 300 mg, q6h or q8h.The treatment period of biapenem was generally 7-14 days. Results The effective rate were 75.73%.The cure rate, markedly effective rate, progressive rate, inefficiency and mortality rate were 22.45%, 41.95%, 23.22%, 10.37% and 2.01%, respectively.The bacterial clearance rate and presumed clearance rate were 42.86% and 47.96%, respectively.Adverse drug reaction rate was 1.10%. Conclusion Biapenem in the treatment of chronic liver disease with acute bacterial infection is safe and effective.
Objective To investigate the effect of dexemdetomidine on inflammatory response and oxidative stress in patients undergoing thoracoscopic surgery for radical treatment of lung cancer. Methods One hundred patients undergoing thoracoscopic surgery for radical treatment of lung cancer were randomly divided into dexemdetomidine group (group A) and control group (group B) (50 in each group) .They were all implemented one-lung ventilation.Patients in group A were infused dexmedetomidine 1 μg·kg-1 as loading dose 20 minutes before anesthesia induction, which finished in 15 min.Then a maintenance dose of dexmedetomidine was continuous infused at a rate of 0.5 μg·kg-1·h-1 until 20 min before operation finished.Patients in group B were given the equal volume of 0.9% sodium choride soution as above.Venous blood samples were collected at 5 min after endotracheal intubation (t0), 30 (t1) and 60 min (t2) of one-lung ventilation, and the end of operation (t3).The serum concentrations of TNF-a, IL-6 and IL-8 were evaluated by ELISA method.The analysis of blood gas was performed and oxygenation index was calculated.The levels of MDA, SOD were also detected . Results Compared with the t0, the activity of SOD decreased, meanwhile, the plasma concentration of MDA, TNF-α, IL-6 and IL-8 increased in both groups at t1- t3(P<0.01).Compared to group B,the activity of SOD were increased in group A at t3,and the plasma concentration of MDA,TNF-α,IL-6 and IL-8 decreased at t1-t3(P<0.01) . Conclusion Dexemdetomidine could inhibit inflammatory response and oxidative stress in patients undergoing radical operation of thoracoscopic lung cancer.
Objective To compare the efficacy of theophylline combined with salmeterol/fluticasone propionate combination product (SFC) with SFC in asthmatic patients. Methods In this study,314 patients were randomly divided into control group and treatment group.In the treatment group, patients received 200 mg theophylline and 50/250 μg SFC twice a day for 24 weeks.And patients in control group received 50/250 μg SFC twice a day for 24 weeks.The outcomes were evaluated by the level of asthma control (assessed by the Asthma Control Test),the number of patients experiencing exacerbation more than once during the 24-week treatment period and lung function tests performed before and after treatment. Results A total of 265 patients completed the trial (135 of the treatment and 130 of control group).There were significantly fewer patients whose asthma exacerbation occurred more than once in the theophylline plus SFC group when compared with the SFC group (29.6%vs.46.9%, P<0.01).Theophylline combined with SFC improved the forced expiratory flow (FEF) from 25% to 75% of vital capacity (FEF25%-75%) value,from (57.4±17.6)% to (66.9±18.8)%,which indicates enhanced small airway function significantly (P<0.01). Conclusion The combination of theophylline and SFC may protect against asthma exacerbations,and improve small airway function.
Cocrystal technology does not change the active ingredients, but improve solubility, thereby improve absorption and bioavailability.Cocrystal technology is an effective method for improving solubility of poorly water-soluble flavonoids.The principle is that hydrogen bonds are formed between hydroxyl groups in flavonoids and conformers to new crystalline,and the original lattice stacking and molecular arrangement changes.This review focus on the research progress of cocrystals of flavonoids and their physicochemical properties and bioavailability, which provide a good reference for the application of flavonoids cocrystals in pharmaceutical.
Objective To optimize the extraction process of white mustard seed varnish and it's matrix ratio by orthogonal design. Methods The extraction process was optimized by L9(34)orthogonal design with the yield of extraction of sinapine thiocyanate,euphadienol,tetrahydropalmatine, and asarinin.The variance analysis method was used to find out the key factors on ethanol reflux extraction and supercritical CO2 extraction process.Paste substrate consists of paraffin, monoglyceride,vaseline,glycerin and so on.The research selected viscosity, hardness,melting property and evenness as indicators to evaluate the formulations.And the L9 (34) orthogonal experiment was used to select the optimal formulation. Results Ethanol concentration significantly affected the extraction of white mustard and Euphorbia kansui (P<0.05),and the amount of solvent only significantly affected the dissolution of euphadienol in Euphorbia kansui (P<0.05).The optimal extraction conditions for the combined extraction were as follows: adding 60% ethanol 13 times the amount of extractand reflux for 1 hour each time.During the supercritical CO2 extraction process extraction of axe pressure had a significant effect for the extraction efficiency of asarinin and corydalis only (P<0.05).The optimum extraction conditions are as follows: extraction pressure 25 MPa,extraction temperature 40 ℃, 95% ethanol as entrainer,which is 3 times the amount of medicinal materials.The key factors affecting the matrix molding paraffin and vaseline is the (P < 0.05),and the optimum ratio of paraffin,monoglyceride,vaseline and glycerin was 2:4:2:1. Conclusion The optimum extraction conditions and the proportion of emulsion paste substrate are determined by orthogonal experiment in this study.The emulsified patch prepared according to the optimized formula has prominent characteristics of high drug loading, good emulsifying property and promoting the transdermal release of drugs.
Objective To study the preparation method of the itraconazole gel formulation,and investigate its drug performance and characteristics in topical transdermal drug delivery. Methods Itraconazole gel was prepared with carbomer 940 as matrix,of which optimal formulation parameters were screened according to the appearance quality test, spreading property, stability and cold-heat resistance by orthogonal experiments.And the drug performance and characteristics of the transdermal delivery of the itraconazole gel formulation were evaluated by a modified Franz diffusion cell technique and HPLC. Results The best formulation parameters were as follows,1% itraconazole,1% carbomer,15% PEG-400 and 10% glycerin.As the in vitro transdermal experiments shown,the time-release curve of itraconazole gel fit well with Higuchi formulation,which indicated that it has a sustained release effect. Conclusion The characteristics of the optimal itraconazole gel is stable with sustained release effect , which may improve the patient compliance.
Objective To evaluate the effect of methimazole and propylthiouracil on liver function in patients with hyperthyroidism. Methods RCTs comparing the effect of methimazole and propylthiouracil on liver function in patients with hyperthyroidism were searched through databases such as CNKI,VIP,WANFANG, CBM,PUBMED,COCHRANE LIBRARY,EMBASE and MEDLINE from inception to October 2017.The quality of the included RCTs was evaluated by Jaded scale.Then, meta-analysis was performed by Revman 5.3.5 software. Results A total of 28 RCTs were enrolled, including 3181 patients.meta-analysis showed that the incidence of liver injury in propylthiouracil group was higher than that in methimazole group[RR=2.73,95%CI (2.23,3.34),P<0.00001], the variation of ALT, AST, ALP and total bilirubin in propylthiouracil group were also significantly larger in propylthiouracil group [SMD=0.68,95%CI(0.46,0.90),P<0.00001;SMD=0.38,95%CI(0.17,0.59),P=0.0005;SMD=0.47,95%CI(0.23,0.72),P=0.0002;SMD=0.70,95%CI(0.45,0.95),P<0.00001]. Conclusion The risk of liver injury in propylthiouracil group is higher than that in methimazole group, suggesting that patients with liver dysfunction be careful in the selection of antithyroid drugs.
Objective To investigate the antibiotic resistance profile of Haemophilus influenzae,Streptococcus pneumoniae, and Moraxella catarrhalis and to provide reference for clinicians' experience treatment. Methods Distribution and antibiotics sensitivity results of Haemophilus influenzae,Streptococcus pneumoniae and Moraxella catarrhalis were retrospectively analyzed in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology during 2015-2017.Analysis of antibiotics sensitivity and comparison of antibiotics resistance rates were performed with WHONET 5.6 and SPSS 11.0, respectively. Results The proportions of Haemophilus influenzae,Streptococcus pneumoniae and Moraxella catarrhalis strains in samples collected from respiratory tract specimens were 99.0%, 84.1% and 99.0% in that hospital during 2015~2017,respectively.The detection rates of beta lactamases of Haemophilus influenzae in adult and children groups were 35.2% and 47.5%,respectively.The sensitivity rates of Haemophilus influenzae to cefotaxime, ciprofloxacin, levofloxacin and chloramphenicol were all above 90%.The resistant rates to ampicillin,ampicillin/ sulbactam,cefuroxime and trimethoprim/sulfamethoxazole in children group were significantly higher than that in adult group (P<0.01).The susceptibility rates of Streptococcus pneumoniae to levofloxacin, moxifloxacin and vancomycin were all above 99.0%.The resistant rates to erythromycin and clindamycin were above 85.0%.The sensitive rates of Moraxella catarrhalis to amoxicillin clavulanic acid and trimethoprim/sulfamethoxazole were above 95.0%.The non-sensitive rates to azithromycin and erythromycin in children group were significantly higher than that in adult group (P<0.01). Conclusion The common fastidious microorganisms in that hospital were mainly from the respiratory tract specimens.In addition, the resistance rates to common antibiotics in children group were higher than that in adult group and attention should be paid to it.
Objective To evaluate the quality of adverse drug reaction (ADR) reports in Shaanxi province from 2015 to 2017, analyze the factors affecting the quality of ADR reports, and provide reference for the standardization and scientificization of ADR reporting. Methods Using the quality scoring system that had been constructed in the previous research, the final selected samples of ADR/AE report were evaluated and statistically analyzed by the scores of 65 indicators. Results About 1.4% of ADR/AE report reached a good level or above.The quality of new and serious ADR reports is relatively good.The quality of ADR/E reported by medical institutions is better than that of manufacturers and enterprises; and the quality of ADR/AE reported by nurses is better than that of doctors, pharmacists and the others.In most reports, these following aspects were better completed: report basic information, ADR analysis, reporter information, reporting unit information, and warnings.However, there were a large proportion of reports were poorly conducted because of the following fields: basic information of patients, information about drugs, and basic information about ADR. Conclusion The quality of ADR/AE report data in Shaanxi province from 2015 to 2017 is poor, and there is an urgent need for improvement.It is necessary to increase the awareness of the reporting entity on the importance of ADR reporting and the professional level of ADR reporting personnel.We should make joint effort in setting a strict ADR report review and evaluation system and improving the function of ADR report online submission network to further improve the quality of ADR reports.
Objective To explore a fast, convenient and labor-saving method of stocktaking with Android mobile devices. Methods A JSP page was placed in the intranet server, and it connected hospital information system (HIS) database by Java DataBase Connectivity (JDBC) method.The theoretical stock data was read and downloaded to Android mobile devices via the wireless router on Intranet.Finally, the stock information was processed by the application (APP) pre-installed on the Android devices. Results With easily achieved mobile inventory, an on-site process system was set with Android mobile phone in the premise of not changing the HIS.The stock information was immediately obtained when checking finished.The APP remarkably increased stocktaking efficiency without increasing much cost. Conclusion A mobile and on-site stocktaking method was established by using Android mobile phones and other mobile devices.It is meaningful and worth trying to improve current work mode of the pharmacy department with new mobile technology.