Chinese Pharmaceutical Journal-Current Issue Current Issue http://journal11.magtechjournal.com/Jwk34_zgyxzz EN-US http://journal11.magtechjournal.com/Jwk34_zgyxzz/EN/current.shtml http://journal11.magtechjournal.com/Jwk34_zgyxzz 5 <![CDATA[Research Progress of Inorganic Nanomaterials for Tumor Ablation Based on Photodynamic Therapy]]> in vitro and in vivo normal tissue cytotoxicity, improves their solubility property in the biological environment and enhances the therapeutic effects. This review introduces the mechanisms of photodynamic therapy, summarizes the use of inorganic nanoparticles in photodynamic therapy, thereby providing a reference for the construction of a more reasonable and effective photodynamic therapy platform integrating inorganic nanoparticles.]]> <![CDATA[Research Progress in Lipid-Regulating Targets]]> st century. Since high blood lipid level was proved to be the main cause of death, lowering blood lipid became the primary means to prevent cardiovascular diseases, and lipid-lowering drugs research is blooming. After decades of development, lipid-lowering drugs have gotten constantly updated. Relevent literature were collected from databases such as CNKI, Wanfang, SionMed, PubMed, and Springer, and drug information were acquired from the National Medical Insurance Service Platform and Pharnex Cloud Database. A review of the targets and classes of lipid-regulating drugs available on the global market is presented, and pending issues in the lipid-regulating research process are discussed.]]> <![CDATA[Qualitative Analysis of Components in the Xylem of <em>Polygala tenuifolia</em> Willd. Based on UPLC-Q TOF-MS/MS and Molecular Network Technology]]> OBJECTIVE To qualitatively and quantitatively analyze the zylem of Polygala tenuifolia Willd. using ultra performance liquid chromatography-quadrupole-time flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with molecular network technnology, as well as HPLC. METHODS The contents of tenuifolin, polygalaxanthone Ⅲ and 3, 6'-disinapoyl sucrose were determined according to the Chinese pharmacopoeia (2020). The chemical components of xylem were identified according to MS/MS fragments combined with SCIEX Traditional Chinese Medicine database, Lipidomics database, reference substance and literature data. Molecular networks were created by combining the similarities of MS/MS fragments. RESULTS The content of tenuifolin, polygalaxanthone Ⅲ and 3,6'-disinapoyl sucrose in the xylem of Polygala tenuifolia Willd. from different regions does not meet the requirement of Chinese pharmacopoeia (2020). A total of 188 compounds were identified in the xylem, including 26 triterpene saponins, 12 xanthones, 69 sucrose esters, 12 flavonoids, 37 lipids, 3 sugars, 3 nucleosides (acids), 8 organic acids, 11 amino acids, and 7 others. CONCLUSION The chemical composition in the xylem of Polygala tenuifolia Willd. are investigated, and the RESULTS provide a basis for the resource utilization as well as further research on the “dysphoria ” material basis.

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<![CDATA[Microstructure and Content Difference of Main and Trace Elements in Cinnabaris and Its Different Processed Products]]> OBJECTIVE To study the differences of microstructure and contents of main and trace elements in cinnabar and its processed products, so as to reveal the scientific connotation of cinnabar processing. METHODS Using thermal field emission scanning electron microscopy (SEM), laser particle size analyzer, X-ray fluorescence spectrometer(XRF), inductively coupled plasma mass spectrometer(ICP-MS)of authentic region in Guizhou province including Wanshan mercury zone cinnabar mineral powder, water fly processed products, wet grinding ball mill instrument of processed products, high temperature vacuum distillation processed products and water remaining residue and so on the different types of cinnabar powder fly method for microstructure and the main trace elements content study. RESULTS The microstructure and contents of main and trace elements in cinnabar were significantly changed before and after processing. After water flying, the particle size of cinnabar decreases and the roundness of grinding becomes worse. After ball milling, the particle size of cinnabar decreases obviously, and the agglomeration phenomenon occurs after standing cinnabar. The particle size of cinnabar increases slightly after vacuum distillation at 300 ℃.After water flying, the content of mercury (Hg) in cinnabar decreases from 71.841% before water flying to 62.906%, the content of sulfur (S) does not change significantly, and the content of oxygen (O) increases from 8.721% before water flying to 13.279% after water flying. After vacuum heating, the content of oxygen in cinnabar increases obviously and that of mercury decreases obviously. The contents of trace elements chromium (Cr), iron (Fe), aluminum (Al), strontium (Sr), zirconium (Zr), barium (Ba), neodymium (Nd), lead (Pb) and rare earth elements in cinnabar increased obviously after water flying. In addition, the content of Zr increased from 2.78 to 78 586 μg·g-1, and zirconia particles were found to be mixed into the cinnabar by SEM. CONCLUSION The microstructure and contents of main and trace elements of cinnabar and its processed products vary greatly, among which the traditional water-flying method is the best processing method of cinnabar, vacuum distillation of cinnabar can provide a new research idea for the processing of cinnabar, and the processing technology of wet grinding of cinnabar by ball mill is worth further discussing.]]> <![CDATA[Correlation Study of Different Hydrophobic Core Polymer Micelles and Their Drug Delivery Properties]]> OBJECTIVE To investigate the drug loading behaviour of polymeric micelles with different hydrophobic cores. METHODS In this study, F127, F108, L64 and P123 with different hydrophilic and hydrophilic balance values in Pluronic family were selected as carrier materials. Puerarin (PUE, LogP=0.41) and daidzein (DE, LogP=2.28) with different degrees of hydrophobicity were used as model drugs. Four blank PMs and eight drug-loaded PMs were prepared by thin-film hydration, and characterized by nanometer particle size tester and transmission electron microscopy. And the hydrophobicity of PM cores was determined by pyrene fluorescence probe. The structural stability of PMs was also analyzed based on the change of drug-loaded particle size over time. Moreover, nuclear magnetic resonance hydrogen spectroscopy was applied to observe the spatial distribution of drugs in PM. Accordingly, the correlation between the above properties and the solubilization effect, drug delivery stability and in vitro release of PM was elucidated. RESULTS Four blank PMs and eight corresponding drug-loaded PMs with uniform particle size (<50 nm) and sphere-like shape were successfully prepared, and the hydrophobic strength of the formed hydrophobic core was P123>L64>F127>F108. The RESULTS show that the solubilization ability of PM for PUE and DE depends mainly on the compatibility of drug and carrier, namely their hydrophobicity difference, while the drug-loading stability and in vitro release of PM are both affected by the compatibility between drug and carrier and the structure stability of PM. CONCLUSION It can be concluded that the PM's structure stability, the spatial distribution of drug within PM and the compatibility between drug and PM all affect the drug delivery performance of PM, which can provide a theoretical basis for the design and development of PM.]]> <![CDATA[Analysis of chemical constituents of Yifei Jiedu Granules by UHPLC-Q Exactive Focus MS/MS]]> OBJECTIVE To establish a high-resolution mass spectrometry method for rapid identification of chemical constituents of Yifei Jiedu Granules. METHODS The composition of Yifei Jiedu Granules was rapidly identified by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitwell high resolution mass spectrometry (UHPLC-Q Exactive Focus MS/MS). The analysis was performed on Thermo Accucore aQ C18 column (2.1 mm×150 mm, 2.6 μm) with mobile phase of methanol (A)-0.1% formic acid (B) for gradient elution (0-3 min, 1%A; 3-7 min, 1%- 2%A; 7-35 min, 2%-95%A; 35-37 min, 95%-2%A; 37-39 min, 1%A). The column temperature was at maintained 35 ℃, the injection volume was 3 μL and the flow rate was 0.3 mL·min-1. The information of the chemical constituents of Yifei Jiedu Granules was acquired in positive and negative ion modes by heated electrospray ion source(HESI), scanning range of 100-1 500 m/z, and collision energy of 30 eV. The chemical constituents of Yifei Jiedu Granules were identified by Xcalibur 4.1 software combined with reference and literature information. RESULTS A total of 186 chemical components were identified, including 38 triterpenoid saponins, 34 flavonoids, 17 phenylethanolsides, 14 phenolic acids, 16 terpenoids, 11 lignans, 11 chromogenic ketones, 10 coumarins, 9 phenolic triglycerides, 3 volatile oils, 3 nucleosides, 2 sugars, 2 phenols, 1 amino acid and 15 other groups. Ten of the compounds were confirmed by comparison with reference materials. CONCLUSION The established method can be used for rapid and accurate identification and analysis of chemical constituents in Yifei Jiedu Granules, which lays a foundation for quality evaluation and research on pharmacodynamic substances and mechanism of action.]]> <![CDATA[Simultaneous Determination of Seven Aristolochic Acid Analogues in Zhennaoning Capsules by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry]]> OBJECTIVE To establish the determination method for aristolochic acid analogues in Zhennaoning Capsules. METHODS A Phenomemex Kinetex (2.1 mm×100 mm, 2.6 μm) column was used with methanol-0.1% formic acid (containing 1 mmol·L-1 ammonium acetate) as mobile phase gradiently eluted at a flow rate of 0.3 mL·min-1. By using multi-reaction monitoring mode (MRM), an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for simultaneous determination of seven aristolochic acid analogues including aristolochic acid Ⅲa, 7-hydroxy aristolochic acid Ⅰ, aristolochic acid Ⅳa, aristolochic acid Ⅱ, aristolactam BⅡ, aristolactam Ⅰ, and aristolochic acid Ⅰ. RESULTS The linear relationships for aristolochic acid Ⅲa, 7-hydroxy aristolochic acid Ⅰ, aristolochic acid Ⅳa, aristolochic acid Ⅱ, aristolactam B Ⅱ, aristolactam Ⅰ, and aristolochic acid Ⅰ were good in the ranges of 1.241-1 240.572, 1.034-1 034.056, 2.109-2 108.709, 1.070-1 070.378, 1.064-1 064.000, 2.154-2 154.022, 1.086-1 085.922 ng·mL-1, respectively. And their respective average recovery rates were 101.8% (RSD 1.84%), 101.9% (RSD 2.67%), 102.2% (RSD 2.74%), 102.1% (RSD 2.13%), 101.8% (RSD 2.60%), 100.7% (RSD 0.96%), 104.1% (RSD 6.15%), respectively. Among ten batches of samples, aristolochic acid Ⅳa, aristolactam Ⅰ and aristolochic acid Ⅰ were detected and the content range was 3.875-6.913, 2.984-6.072 and 0.350-1.719 ng·g-1, respectively, meanwhile, there were no aristolochic acid Ⅲa, 7-hydroxy aristolochic acid Ⅰ, aristolochic acid Ⅱ and aristolactam B Ⅱ detected. CONCLUSION The established UHPLC-MS/MS method is accurate and reliable. Aristolochic acid Ⅳa, aristolactam Ⅰ and aristolochic acid Ⅰ were detected in Zhennaoning Capsules. Among them, aristolochic acid Ⅳa and aristolactam Ⅰ have low toxicity or no obvious toxicity, while the toxin substance is aristolochic acid Ⅰ with nitro group. Because the content of aristolochic acid Ⅰ in some samples exceeds the limit, it suggests that the content of aristolochic acid Ⅰ in this preparation needs to be strictly controlled.]]> <![CDATA[Impurity Control of Leuprorelin Acetate Microspheres for Injection]]> OBJECTIVE To compare and analyze the impurity profile of leuprorelin acetate microspheres, discuss the stability of microspheres under high humidity condition, and put forward the impurity control strategy. METHODS The structures of impurities in polylactic acid(PLA) microspheres were identified by high resolution liquid mass spectrometry (HPLC-MS/MS), the impurity profiles of different polymers and microspheres from different vendors were compared and analyzed by high performance liquid chromatography (HPLC), the stability of microspheres under high humidity condition was investigated in constant temperature and humidity chamber, and the hygroscopic characteristics of microspheres were analyzed by dynamic water adsorption analysis (DVS). RESULTS For PLA and PLGA microspheres from the same manufacturer, the difference in impurity profile was mainly reflected in the types of acylated impurities; for PLGA microsphere from different manufacturers, the difference in impurity profile was reflected in the type of process impurities. CONCLUSION There are 5 and 8 special kinds of acylated impurities in PLA and PLGA microspheres, and the acylation sites are the serine residue of the peptide chain. Different polymers lead to different types of acylated impurities. PLA and PLGA microspheres show hygroscopicity and should be stored in low humidity environment.]]> <![CDATA[Optimization of Rapid Evaluation Method and Evaluation Criteria of Drug Hepatotoxicity Based on Zebrafish Larvae Model]]> OBJECTIVE To establish a rapid evaluation method of hepatotoxicity and a grading method of drug liver injury based on zebrafish larvae model taking acetaminophen (APAP) as an example by optimizing the influencing factors and parameters for evaluation of its hepatotoxicity on zebrafish larvae. METHODS Zebrafish larvae were treated with different concentrations of acetaminophen (APAP). The mortality of zebrafish in different treatment groups was counted at the end of the experiment (48 h/24 h after drug exposure), and the mortality-concentration effect curve was drawn, and 0% lethal concentration (LC0) and half lethal concentration (LC50) were calculated. The relevant influencing factors of zebrafish larvae in APAP toxicity study were investigated and optimized, including zebrafish age [3 dpf, 4 dpf (day post fertilization:dpf)], exposure time (48 h, 24 h) and well plate (6 well plate, 12 well plate, 6 mL, 4 mL), and orthogonal experiments were designed from the above three levels to establish the best experimental conditions and parameters of the zebrafish hepatotoxicity model. In addition, 3 dpf larval zebrafish (3 dpf-48 hpe-12 well plate) was selected for comparison with the selected conditions (4 dpf-24 hpe-12 well plate)(hour post exposure: hpe). Phenotypic evaluation, histopathological evaluation, apoptosis evaluation in vivo, biochemical indexes and liver area were used as system biological evaluation indicators to confirm the method and damage reference standard for overall hepatotoxicity evaluation of zebrafish. RESULTS Taking the LC50 of each group obtained from the experiment as the index, the optimal experimental parameters for establishing the hepatotoxicity model were obtained through orthogonal experiment optimization: 4 dpf larval zebrafish was selected to be exposed to the drug for 24 h in a 12 well plate. The RESULTS showed that compared with the control group, the liver transparency of zebrafish larvae in each exposure group was decreased, the color became dark, and the absorption of yolk sac was delayed. The structure of livertissue was loose, the vacuolization of liver cells was severe; and acridine orange staining showed yellow green fluorescence, indicating the existence of hepatocyte apoptosis. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were increased significantly. The liver area showed a dose-dependent reduction, which confirmed the rationality of the method. The RESULTS of correlation analysis proved the reliability of using the change value of liver area (δ) to evaluate the liver injury of zebrafish larvae, and the liver injury rating of zebrafish larvae was preliminarily established based on this index. CONCLUSION The best acute toxicity evaluation parameters of zebrafish larvae are investigated and optimized, the liver toxicity evaluation method of zebrafish larvae is confirmed, and the liver injury rating of zebrafish larvae is established, which provides a reference for rapid evaluation of drug hepatotoxicity based on the zebrafish larvae model.]]> <![CDATA[Safety of Multi-oil Fat Emulsion in Parenteral Nutrition of Extremely Low Birth Weight Infants]]> OBJECTIVE To compare the safety of multi-oil fat emulsion (SMOFlipid) and soybean oil-fat emulsion (Intralipid) in parenteral nutrition of very low birth weight infants (VLBW), respectively. METHODS Through retrospective medical record data study, the VLBW admitted to the neonatal department of our hospital from 2016 to 2022 were selected as the research objects. According to the inclusion and exclusion criteria, the clinical characteristics, clinical complications and related outcomes of VLBW in the Intralipid group and the SMOFlipid group were compared. RESULTS A total of 273 VLBW patients were included in the study, 117 in the Intralipid group and 156 in the SMOFlipid group. The two groups were similar in terms of gestational age at birth, sex and weight. SMOFlipid was associated with shorter hospital stay (68 d vs. 81 d, P<0.001). The incidence of retinopathy of prematurity was lower in the SMOFlipid group (31.4% vs. 46.2%, P=0.013), but multivariate regression analysis showed no statistical difference (OR 0.557,95% CI[0.287, 1.082], P=0.084). There were no statistically significant differences in mortality, cholestasis, and other diseases such as bronchopulmonary dysplasia between the two VLBW groups. CONCLUSIONS Compared with Intralipid, SMOFlipid has a similar safety profile in the VLBW population.]]> <![CDATA[Novel GIP/GLP-1 Dual Receptor Agonist Tirzepatide]]>