To analyze the current status of pediatric drug clinical trials in China so as to provide reference for its improvement.

Information about pediatric drug clinical trials was collected from the clinical trials explicitly labeled of CDE. The clinical trial type, clinical trial stage, recruitment, insurance and DMC were analyzed statistically by ratio analysis method.

By June 2020, 10 933 clinical trials had been registered on the platform, including 139 pediatric drugs. Among these pediatric drug clinical trials, phase Ⅲ clinical trials had the largest number. In aspect of drug classes, biological products had the largest number of clinical trials, followed by chemical drugs, while traditional Chinese medicine had the least registration number. In addition, the enthusiasm of children's drug companies in China for new drug research and development is not high. There are some problems in pediatric drug clinical trials, such as the long trial period and difficult recruitment of subjects.

To optimize the refining technology of maggots oil and study the effect of refined maggots oil on skin aging induced by D-galactose in mice.

The effects of different factors on the refining technology (including hydration degumming and deacidification by alkali-refining) of maggots oil were investigated, and the physical and chemical properties of maggots oil were analyzed. Female Kunming mice were randomly divided into normal group, model group, matrix group, vitamin E group, low dose and high dose refined maggots oil groups. Except for the normal group, the mice in the other groups were subcutaneously injected 3% D-galactose into the back of the neck for 42 consecutive days to establish the subacute aging model. The mice in each administration group were smeared with corresponding drugs once a day for 32 days. HE staining was used to observe the micromorphology of skin tissue, and the contents of water, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), hydroxyproline (HYP) and malondialdehyde (MDA) in the skin were detected. Ten rabbits were divided into normal group, intact skin group and damaged skin group. The skin irritation test was conducted on rabbits. Twelve rabbits were divided into normal group, intact skin group and damaged skin group. The rabbits were given 0.5 mL maggots essential oil on the left side of the back and olive oil of the same volume on the right side, once a day for 7 days. The irritation effect of the drug on the rabbit skin was observed, and the skin erythema and edema were scored. The skin of the administration site was stained with HE at 72 h after the last administration, and the skin tissue morphology was observed.

After refining, the iodine value, acid value, peroxide value and saponification value of maggots oil were (18.714±0.116) g·100 g^-1, (0.465±0.006) mg·g^-1, (0.016±0.001) g·100 g^-1 and (130.212±1.623) mg·g^-1, respectively, which conformed to the national standard of the massage essential oil and emollient oil. Compared with the model group, the dermis of mice in the maggots essential oil groups were thickened, the numbers of hair follicles and collagen fibers, the contents of water, HYP, SOD and GSH-Px in the skin increased significantly (P<0.05, P<0.01), the content of MDA decreased significantly (P<0.01). In the rabbit skin irritation test, the erythema and edema score of each group were 0, and the skin irritation was evaluated as no irritation.

Maggots essential oil has anti-aging effect on mouse skin induced by D-galactose without irritation, and has potential application value. The color, smell, clarity and fluidity of maggots essential oil are improved after refining, which provides the basis for the development of anti-aging products of maggots essential oil.

To study the optimal formulation process of betastin ethosomes and investigate its transdermal permeation in vitro.

Betastine ethosomes were prepared by ethanol injection method. The dosage of soybean lecithin, ethanol and water bath temperature were taken as investigation factors, particle size and entrapment efficiency were determined as evaluation indexes, and the formulation was optimized by central composite design-response surface methodology. The preliminary stability of the preparation was also investigated. Transdermal absorption test in vitro was carried out by using Franz diffusion cell to compare the effects of different ways of administration on the transdermal penetration of betastine.

The optimum prescription conditions were as follows: betastine 100 mg, soybean lecithin 311 mg, ethanol 4.1 mL, water bath temperature 39 ℃. The preparation was clear liquid with blue light, the encapsulation rate was (67.1±2.23)%, the particle size was (59.6±4.81) nm, and the difference between the actual value and the predicted value was less than 5%. The transdermal permeation rate of betastin (10.76 μg·cm^-2·h^-1) was 8.47 times of that of aqueous solution, 3.09 times of that of ordinary liposomes, and 1.63 times of that of 45% ethanol solution.

The prepared betastol ethosomes has the advantages of small particle size, uniform distribution, high stability and good transdermal absorption.

To establish the first batch of national reference standard of brimonidine tartrate.

The structure of brimonidine tartrate was confirmed by IR, NMR and LC-MS spectroscopy. The purity of brimonidine tartrate was determined by HPLC. Moreover, the residual solvents, residual ignition and moisture were determined. The content of brimonidine tartrate was calculated by mass balance method.

The structure of brimonidine tartrate was confirmed. The content of brimonidine tartrate was assigned as 99.8%.

The first batch of national reference standard of brimonidine tartrate can be applied for the identification and content determination of brimonidine tartrate and its related preparations.

To establish an LC-MS method for the determination of two phenylhydrazine-like genotoxic impurities [(4-sulfamoylphenyl) hydrazine, SHH; (4-methyl-acetophenone) para-sulfonamide phenylhydrazine, MAP] in celecoxib.

The separation was established on Thermo BDS Hypersil C₁₈(100 mm×4.6 mm, 2.4 μm) column by liner gradient elution using (0.1% ammonium formate-0.1% formic acid buffer solution)-methanol 90∶10 as mobile phase A and methanol as mobile phase B. 5 mmol·L^-1 dithiothreitol buffer solution was used as the antioxidant, the determination was carried out by multiple reactions monitoring mode with positive electrospray ionization, meanwhile, the analytes were quantitatively determined by internal reference method.

The established LC-MS method displayed satisfactory linearity over the concentration range of 20~200 ng·mL^-1. The average recovery was 99.7% (RSD=6.0%) for SHH and 97.6% (RSD=5.1%) for MAP. The limit of detection and limit of quantification were 10 ng·mL^-1 and 20 ng·mL^-1, respectively. The reference and test solutions were stable at 4 ℃ for 4 h.

The established LC-MS method is suitable for simultaneous determination of SHH and MAP genotoxic impurities in celecoxib.

To analyze and evaluate the clinical use of antifungal drugs for deep tissue infections in a third-grade A specialized hospital from 2017 to 2019, and provide reference for the rational and standardized use.

The use data of antifungal drugs for deep tissue infections were extracted by the information system and analyzed by ranking of the sales amount and DDDs.

The sales amount and proportion of antifungal drugs for deep tissue infections in the hospital showed a gradual downward trend from 2017 to 2019. The azoles, amphotericin B and its liposomes, and echinocandins were the three kinds of most frequently used drugs. The DDCs of echinocandins and amphotericin B were the highest. The DUIs of some drugs were greater than 1.

The use of antifungal drugs for deep tissue infections in this hospital is decreasing year by year, and the overall structure is relatively stable. It is necessary to reasonably hold the indications for the use of antifungal drugs, standardize the dose and course of treatment, and promote the rational use of antifungal drugs according to specific clinical conditions.