As children are extremely sensitive to the bad taste of medicine,they have poor compliance with the bitter medicine.It is of great importance to develop the approaches of taste masking for the research of paediatric drug formulations.Besides,taste masking technology is one of the main barrier to develop children pharmaceutic preparation.This article provides an overview of the advance in taste masking technology of oral paediatric medicine in recent years,and introduces five types of taste masking technology in terms of drug,preparation and the bitter taste transduction,including principle and characteristics of these approaches,as well as their application in formulations,so as to provide some references for the development of paediatric medicine.

Objective To investigate the protective effect of n-butanol extract from the roots of Potentilla anserina (NP) on hypoxic hippocampal neurons in neonatal rats.Methods Primary cultured hippocampal neurons were pretreated with different concentration of NP (0.25,0.0625,and 0.0156 mg/mL) before incubation in a low oxygen (0.1％) environment for 4 h.Cell viability was evaluated by Trypan blue staining assay.Lactate dehydrogenase (LDH) released by neurons into the medium was measured.The activity of superoxide dismutase (SOD) in cell cytosol was determined using nitroblue tetrazolium.Morphological changes and mitochondrial function were observed by transmission electron microscopy.Results Hypoxic injury could decrease the cells viability of neuron,enhance LDH release (P ＜ 0.05),decrease SOD activity,and increase mitochondrial injury.Pretreatment with NP significantly increased cell viability,decreased LDH release (P ＜ 0.05),promoted SOD activity (P ＜ 0.05),and remarkably improved cellular ultra-microstructure compared with the model group.Conclusion NP could protect the primary hippocampal neurons from hypoxic injury by attenuating mitochondrial cell death.

In China, the incidence of adverse reactions of drugs in children is twice that in adults; especially in the newborns, it is four times that in adults. The main reason is that the physiological characteristics of children are changing constantly due to that they are in a constant process of growth and development; while the pediatric medicines cannot meet the clinical needs of children in different age states. Accordingly, the development of pediatric medicines, especially oral solid preparations which are convenient for administration and storage, has attracted a lot of attention. This review introduced various pediatric oral solid dosage forms such as multiparticulates, orally disintegrating tablets(ODT)and chewable tablets. In addition, the efficient taste masking technology and accurate dose control were the further research directions for development of pediatric medicines, which would provide important theoretical references for studies on pediatric oral solid dosage forms in future.

Liquid preparations are the commonly used oral dosage forms in pediatric clinical practice.This review introduces the pediatric oral liquid dosage forms including extemporaneous preparation of oral liquid formulations, oral liquid sustained and controlled release formulations, nanosuspensions, nanoemulsions, self-nanoemulsions and milk-based liquid formulations.In addition, the efficient flavoring and taste masking technologies, using safe pharmaceutical excipients, high-demanding technical standards and verification strategies, establishing excellent workflow management systems can contribute to the development and application of pediatric oral liquid dosage forms which are safer, more effective and better compliant.This review is helpful in laying the relevant theoretical foundation for further studies on pediatric oral liquid dosage forms.

To mask the bitterness of azithromycin（AZI） and improve patient compliance, an AZI-loaded microsphere (AZI-EC MS) for oral administration was prepared by O/W emulsion solvent evaporation with ethylcellulose (EC) as carrier. The release profiles and taste-masking effect of AZI-EC MS were preliminarily assessed. Its physical properties and morphology were then investigated by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The results indicated that the polymer weight of EC could influence the drug release behavior. With a drug polymer ratio of 1∶1 and mixed EC (N22/T10, 7∶3) as carrier, the cumulative release of AZI-EC MS at 0.5 h was less than 40% and reached 90% at 8 h; the drug loading efficiency of microspheres was (48.95 ± 0.86)% with smooth spherical morphology. The AZI bitterness threshold is 9.93 μg/mL with a strong bitter taste, which indicated a better taste masking effect. Therefore, AZI-EC MS prepared in this study can mask AZI bitterness and improve patient compliance, setting the stage for the research of new AZI preparations.

In order to mask the bitterness of azithromycin (AZI) and individually regulate the drug release rate to reduce gastrointestinal irritation, immediate-release AZI-AmberliteTM IRP64/HPC and delayed-release AZI-AmberliteTM IRP69/RS100 were prepared by modifying with hydroxypropyl cellulose (HPC) and Eudragit RS100, respectively, and further combined to achieve controlled release.The drug loading and drug utilization rate of AZI-ion exchange resin complexes were measured; the structure of AZI-ion exchange resin complexes was characterized by differential scanning calorimetry and X-ray diffraction; and the wetting humidity, odor masking effects, in vitro dissolution and release behaviors were determined.The results showed that the formation of AZI-ion exchange resin complexes changed the original crystallization state of the drug, that the 2.5% HPC-modified AZI-AmberliteTM IRP64/HPC and the 0.5% RS100-modified AZI-AmberliteTM IRP69/RS100 demonstrated good taste masking effect, and that their combination in the drug content ratio of 13∶67 achieved the expected drug release behavior, i.e.rapid release of AZI in the first 10 min and smooth release in the later 6 h.These results indicated that the AZI-ion exchange resin complexes prepared by surface modification and their composites could mask the bitterness of AZI and realize the flexible adjustment of drug release rate, which lays the foundation for the research and development of new AZI preparations.

To enhance the quality control of tebipenem pivoxil and establish its quality criteria,the synthetic route of tebipenem pivoxil was analyzed and five related substances (P1,P2,P6,P8 and P9)were synthesized and characterized by 1H NMR and MS.The purities of the related substances were over 95% via HPLC detec-tion.The target compounds can be used as the reference of the related substances in the quality control of tebi-penem pivoxil.The starting materials were cheap and easy to obtain;the reaction conditions were mild.

This study sought to assess the therapeutic effect of celecoxib (CEL)-loaded polylactic acid-glycolic acid copolymer (PLGA) microspheres on rheumatoid arthritis in rats after intra-articular injection.The celecoxib-loaded microspheres (CEL-MS) were prepared by the O/W solvent volatilization method with PLGA as carrier.In order to investigate the therapeutic effect of CEL-MS on rheumatoid arthritis in rats after intra-articular injection, a rat model of adjuvant arthritis (AA) was constructed by complete Freund''s adjuvant, and the evaluation indicators of the therapeutic effect were rat paw swelling, arthritis index,spleen index and joint synovial histopathological examination. The results showed that the microspheres had a smooth spherical morphology with a particle size of (2.1 ± 0.3) μm and a drug loading efficiency of (20.8 ± 0.6)%.The results of the in vivo efficacy test showed that intra-articular injection of CEL-MS compared to the CEL suspension oral and the celecoxib suspension intra-articular injection in adjuvant arthritis rat model can significantly reduce joint swelling and arthritis index, thus effectively inhibiting synovial inflammation.The above results indicate that intra-articular injection of CEL-MS has a good therapeutic effect on rheumatoid arthritis in rats.

Objective To identify the significance of serum phospholipase A2 receptor antibody (PLA2R-Ab) in idiopathic membranous nephropathy (IMN) patients.Methods A total of 108 patients diagnosed as IMN by medical history,physical examination,laboratory examination and renal biopsy in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Dec 1,2014 and Aug 31,2017 were enrolled,and all related data were recorded.According to the results of serum PLA2R-Ab test,patients were divided to positive group and negative group,and the data were compared with the independent sample t test and the chi-square test.Kaplan-Meier survival analysis was performed to compare remission rates between groups,and the Logrank method was used to evaluate the significance of differences.Univariate and multivariate Cox regression analysis were used to verify predicting factors for achieving remission.Results Overall,67.6％(73/108) patients had detectable serum PLA2R-Ab.Compared with patients in negative group,patients in positive group exhibited higher proportion of male patients (P=0.002),lower level of serum albumin (P ＜ 0.001),higher level of cholesterol (P ＜ 0.001),lower level of immunoglobulin G (P ＜0.001),higher level of proteinuria (P=0.003),a lower of chance of remission (P=0.049),longer time needed to achieve partial remission (P=0.001) and complete remission (P=0.002).The 1-and 2-year cumulative renal partial remission rates were 72.4％,86.1％,and the cumulative renal complete remission rates were 43.8％,54.0％,respectively.Patients in negative group had higher partial remission (x2=9.84,P=0.002) and complete remission (x2=15.50,P＜0.001) than those in positive group.Multivariate Cox regression model indicated that serum positive PLA2R-Ab was a significant independent risk factor.Conclusions IMN patients with serum PLA2R-Ab show more severe condition and lower remission rates than those without serum PLA2R-Ab.Serum positive PLA2R-Ab is an independent remission-related predictor for IMN patients.

Objective To investigate the clinical characteristics and risk factors of secondary infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods One hundred and eighteen patients newly diagnosed with AAV at the institute of nephrology,Tongji hospital affiliated to Huazhong university of science and technology,from 2012 to 2017,were analyzed retrospectively.Induction therapy included single corticosteroids,combination of corticosteroids with cyclophosphamide and combination of corticosteroids with other immunosuppressive agents.End point was defined as moderate to severe infection which was diagnosed by the clinical and radiological manifestation as well as microbiological evidences.The infection-related survival curve was drawn to reflect the time when the infection occurred.The clinical baseline variables in patients with and without infection were compared.Multivariate Logistic regression model was used to determine the independent predictors of infection.Receiver-operating characteristic curve (ROC) was plotted for evaluating the predictive value of lymphocyte on moderate to severe infection.Results During followup of median 3 months (1-30 months),88 infection episodes were found in 63 (53.4％) patients,of which 54 times (61.4％) occurred within 6 months after treatment,46 times (52.3％) happened within 3 months after treatment.The most common organ of infection was lung (62.5％),and the most common pathogen was bacteria (51.1％).Multivariate Logistic regression model showed that lung involvement (OR=4.44,95％ CI 1.59-12.41),moderate reduction of lymphocyte in follow-up (OR=5.69,95％ CI 2.05-15.85) and severe lymphocyte reduction (OR=36.28,95％CI 3.45-381.17) were independent risk factors of secondary infection in AAV patients (all P ＜ 0.05).ROC curve showed that the area under the curve of lymphocyte as a predictor of severe infection was 0.767 (95％ CI 0.64-0.89,P ＜ 0.05).Based on lymphocyte less than 0.49× 109/L which was the cut-off value for predicting severe infection,the sensitivity and the specificity were 83.9％ and 71.9％,respectively.Conclusions Lung involvement and moderate-severe lymphopenia during follow-up are independent risk factors of secondary infection in AAV patients.Hence,physician should pay more attention to those patients,and adjust treatment in time to avoid the occurrence of infection.