OBJECTIVE To build a text-convolutional neural network(Text-CNN)-based prediction model for anti-Staphylococcus aureus(S.aureus) activity and identify anti-S.aureus hits by virtual screening. OBJECTIVE A dataset containing 26327 compounds annotated with S.aureus activity data was collected and curated from the ChEMBL database. Ten pairs of training and test sets were generated by random partition for 10 times and then 10 models were built using the Text-CNN algorithm. The best-performing model was determined by model evaluation and further studied by Y-randomization test and applicability domain analysis. Following that, the best-performing model was used to virtually screen the in-house chemical library, by which the potential antibacterial agents were determined. The micro-broth dilution method was used to test anti-S.aureus activity of the potential hits. RESULTS The machine-learning model(named Text-CNN3) performed well in classification. Evaluated on the test set, its Mathews correlation coefficient was 0.573 and the area under the ROC curve was 0.881. With this model for virtual screening as well as antibacterial screening, compounds Y5 and Y7 were identified as antibacterial compounds, with minimum inhibitory concentrations(MIC) of 8 and 4 μg·mL^-1, respectively. CONCLUSION The Text-CNN3 model in this study is effective to identify anti-S.aureus compounds, while the antibacterial hits Y5 and Y7 are worthy of further study.

OBJECTIVE To verify the accuracy of the “water content-conductivity fitting curve” model for determining the critical point of microemulsion O/W phase, and to further use this model to optimize the microemulsion of tanshinone extract. OBJECTIVE The “water content-conductivity fitting curve” model was used to determine the phase critical point of microemulsion into O/W type. According to the proportion of microemulsion oil phase, total surfactant and water phase, the pseudo ternary was drawn using Origin 2021 software. The phase diagram was used to screen out the proportions of the larger milk-forming areas; the average particle size and PDI of the microemulsion were used as the inspection indicators, and the star point design-response surface method was used to optimize the microemulsion; high-speed centrifugation and standing at 4 ℃ and 25 ℃ for 60 days, to examine the stability of the microemulsion. RESULTS The optimized microemulsion formulation was(18.11% medicated oil phase, 61.21% Tween 80, 20.68% 1,2-propanediol, the water critical point is 64.29%), K_m was 2.96, preparation temperature was 27.4 ℃, under different experimental conditions, the stability of the microemulsion was good. CONCLUSION The O/W phase critical point determined by the “water content-conductivity fitting curve” model has high accuracy, and the optimized microemulsion has good stability, which achieves the expected research goals.

OBJECTIVE To synthesize p-toluenesulfonic acid(PTS) and famotidine(FMT) cocrystal in order to improve thesolubility of famotidine in water and the permeability. OBJECTIVE The cocrystal was prepared by solvent evaporation method combined with ultrasound. The cocrystal was characterized by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy and powder X-ray diffraction. The single crystal structure of FMT-PTS-H₂O(1∶1∶1) was successfully obtained, and the solubility and permeability of the newly synthesized cocrystal were studied. RESULTS After the formation of cocrystal, the water solubility and permeability of FMT increased by 1.54 and 2.29 times, respectively. CONCLUSION Compared with FMT, the solubility and permeability of FMT after the formation of cocrystal were improved. This study provides a method for improving the permeability of biopharmaceutics classification system(BCS)Ⅲ drugs, which will contribute to the development of low permeability drugs.

OBJECTIVE To establish a method for the determination of 32 elements in COVID-19 vaccine. OBJECTIVE The 32 elements were determined by inductively coupled plasma optical emission spectrometer(ICP-OES) through semi-quantitative screening and quantitative detection, and the specificity, linearity, limit of quantification, detection limit and recovery rate of the ICP-OES method were investigated to evaluate the feasibility of the method for the detection of trace elements in vaccines. RESULTS The linear relationship of each element was good within the detection mass concentration range, and the recoveries of element added were 94.06%-115.50%. When applied to the detection of the samples at each accelerated placement point, except for the trace contents of B and Si elements, which did not increase significantly after long-term placement, the contents of other elements were far less than the prescribed limits. CONCLUSION The ICP-OES method is established. And the method has good specificity, reliable results, simple and rapid, and is suitable for the determination of 32 elements in COVID-19 vaccine.

OBJECTIVE To analyze the quality differences of Cyathulae Radix from different manufacturers on the market based on national drug sampling and testing in 2022, then analyze the problems and put forward suggestions to provide basis for the quality supervision and standard improvement of Cyathulae Radix. OBJECTIVE Inspection was conducted according to corresponding standards, inspection reports were issued, and then quality evaluation and analysis were conducted. At the same time, problems were found and suggestions were made based on targeted exploratory research on quality problems, standard problems and other related problems found in the inspection. RESULTS A total of 334 batches of Cyathulae Radix samples were taken. According to the standard inspection, two batches of samples were found to be substandard in character, and Cyathulae capitatae Radix was used as Cyathulae Radix. At the same time, it was found that the content determination methods in the standard were too complex, and the specified limit for content determination was too low. In the exploratory study, the unique component achybidensaponin I was detected in 27 batches of Cyathulae Radix and 7 batches exceeded the specified limit, which was mixed with Achyranthes bidentata. Plant growth regulator (paclobutrazol) was detected in 270 batches of Cyathulae capitatae Radix. The detection of heavy metals and harmful elements cadmium(Cd) in 114 batches exceeded the limit. Finally, the quality standard of Cyathulae Radix was improved, the supplementary test method was established, and the risk warning was put forward. CONCLUSION Through the national sampling inspection, the relevant problems in the prepared slices and quality standards of Cyathulae Radix are found, suggesting that the quality standards should be improved and the quality supervision of Cyathulae Radix should be strengthened.

OBJECTIVE To explore an evaluation method of sterile operation in pharmacy intravenous admixture services(PIVAS). OBJECTIVE The US intravenous quality assurance(IVQA) media fill test kit was used to verify the aseptic operation of the mixed dispensing personnel in our hospital, and the feasibility of applying the media fill test in the PIVAS was preliminarily explored. RESULTS The media fill test was easy to operate without harsh culture conditions and testing equipment. The test results were different under two different mixing conditions, which can verify the operation of personnel. CONCLUSION The media fill test is applicable to the quality control of personnel in sterile dispensing operations.

Rectal in situ gel combines the double characteristics of gel and rectal administration, and has become the focus of pharmaceutics research. Rectal in situ gel is a kind of non-chemical crosslinked semi-solid gel which can be transformed from liquid to gel immediately after administration in solution. It has unique reverse hot gel properties, good sustained release effect and high bioavailability. Referring to the relevant literature at domestic and abroad in the past 10 years, the characteristics, preparation technology, quality evaluation methods and application of rectal in situ gel were summarized.By analyzing the research progress of rectal in situ gel new ideas for the research and development of efficient rectal administration preparations are provided.

Euphorbia pekinensis is a traditional medicine of draining water, dispersing swelling and dissipating binds, first recorded in Shennong's Herbal Classic of Materia Medica. E. pekinensis is used to treat edama, phlegm-fluid retention, carbuncle swollen and toxic and other disease. The major components of E. pekinensis include diterpenoids, triterpenoids, flavonoids, coumarins, organic acids and tannins. E. pekinensis has always emphasized the use of processed products as medicine due to strong toxicity. After processing, its drug properties and chemical components are changed, under heating and acidic conditions, diterpenoids undergo oxidation, hydrolysis and rearrangement, which lead to structural transformation and decrease in content, while glycoside-containing compounds undergo hydrolysis, resulting in an increase in the content of aglycones. This paper summarizes the processing history, composition changes, pharmacological effects and toxicity comparison of E. pekinensis by consulting literature over the years, which provides reference for the rational development and utilization of medicinal material resources of E. pekinensis.

OBJECTIVE To investigate the non-clinical safety and immunogenicity of recombinant group B meningococcal vaccine by repeatedly dose to rats, so as to provide reference for designing dose level and monitoring toxicity and side effects in clinical trials. METHODS SD rats were used to design 4 main toxicity groups including negative control group, adjuvant control group, low dose vaccine group (1 dose each) and high dose vaccine group (3 doses each) and 3 satellite groups. The vaccine was dosed by intramuscular injection at weeks 0, 3, 6, 9 and 12 respectively. During the study, all the animals of the main toxicity group were observed for clinical signs, indicators such as body weights, food consumption, body temperature, blood cells counting, coagulation, serum biochemistry, ophthalmology, T lymphocyte subsets and cytokines were detected. Serum specific IgG antibody and bactericidal antibody were measured for satellite animals. All the animals were observed anatomically, main organs were weighed to the calculate viscera/body ratio and the viscera/brain ratio, and various tissues and organs were examined pathologically. RESULTS It could produce high-leveled binding antibodies and bactericidal antibodies with strong activity in immune serum that rats injected the low and high doses of recombinant group B meningococcal vaccines. Both the low and high dose vaccines caused the increases in neutrophils, monocytes and lymphocytes significantly, the decreases in hemoglobin and RBC significantly. Other dose-related changes involved the increase in serum globulin and decrease in albumin, with concomitant decrease in A/G, which basically returned to normal after 4 weeks of recovery period. The histopathological findings associated with adjuvant and vaccine were mild or moderate granulomatous inflammation, acute inflammation in injection site, infiltration and proliferation of mononuclear cells/mixed cells in the sciatic membrane, and increased number of myeloid plasma cells and granulocytes in lymph nodes. CONCLUSION Recombinant group B meningococcal vaccine had good immunogenicity and safety profile in SD rats, there is no immune toxicity reaction. It is obvious that adjuvant and vaccine-related changes in indicators of peripheral blood and the inflammation response in injection site. Under the dose levels of this study, there is no adverse effect level on recombinant B group meningococcal vaccine for 3 doses/one rat.

OBJECTIVE To establish the fingerprint of the substance benchmark of Qianghuo shengshi decoction (QSD) and the determination method of multi-index composition content, study the transfer rule of the substance benchmark value of QSD, and provide a scientific basis for the subsequent development of QSD and quality control evaluation. METHODS Fifteen batches of QSD substance benchmark samples were prepared according to the method recorded in ancient medical books, and their fingerprint was established and evaluated, its characteristic peaks was clarified and assigned to the characteristic peaks, and we complete the content determination and transfer rate calculation of the 8 index components in the QSD substance benchmark. RESULTS The similarity of the fingerprint of 15 batches of QSD substance benchmark was between 0.882 and 0.938. A total of 24 common peaks were identified, and 8 common peaks were identified as chlorogenic acid, prim-O-glucosylcimifugin, ferulic acid, senkyunolide I, 5-O-methylvisammioside, ammonium glycyrrhizinate, notopterygol, osthole. The paste yield of 15 batches of QSD was 22.54%-29.92%, and the average paste transfer rate was 70.69%. The content and average transfer rate of each index component from decoction pieces to substance benchmarks were 0.077 2%-0.106 6% and 128.05% for chlorogenic acid,prim-O-glucosylcimifugin 0.015 5%-0.023 8% and 120.26%, ferulic acid 0.047 5%-0.076 0% and 114.49%, senkyunolide I 0.006 6%-0.008 9% and 132.93%, 5-O-methylvisammioside 0.007 2%-0.009 9% and 90.27%, ammonium glycyrrhizinate 0.181 6%-0.273 5% and 80.53%, notopterygol 0.000 7%-0.001 3% and 50.97%, osthole 0.000 9%-0.002 2% and 13.67%. CONCLUSION In this experiment, a combination of fingerprint, paste yield and multi-index composition content determination could be used to analysis the transfer rate of QSD decoction pieces to substance benchmarks, and provide a method reference for the quality control and subsequent development of this prescription.