OBJECTIVE To predict the potential quality marker (Q-Marker) components of Suanzaoren Decoction based on the prototype chemical composition of in vivo by using network pharmacology. METHODS Firstly, the plasma samples and urine samples of rats were collected within 4 h and 24 h after intragastric administration of Suanzaoren Decoction, respectively. Then, based on the chemical components found in vivo, the key action targets and key pathway were obtained by network pharmacology, and the network map of "component-target-pathway" was carried out to predict the quality markers of Suanzaoren Decoction against insomnia, anxiety and depression. RESULTS A total of 20 prototype compounds were detected in rats. The 23 core targets were predicted and 14 prototype components associated with pharmacodynamic efficacy were screened through network pharmacology, the 14 components including jujuboside A, enoxolone, ferulic acid, magnoflorine, liquiritigenin, isoliquiritigenin, poricoic acid A, spinosin, coclaurine, timosaponin BII, glycyrrhizic acid, jujuboside B, liquiritin and senkyunolide A played multiple targets and multiple pathways to regulate insomnia, anxiety, depression. CONCLUSION It is predicted that the 14 chemical components are considered as potential quality markers of Suanzaoren Decoction by analyzing prototype chemical composition in vivo combined with network pharmacology. The results can provide reference for the quality control of Suanzaoren Decoction, and lay a foundation for elucidating the mechanism of its pharmacodynamic substances.

OBJECTIVE To explore the antiepileptic activity of QO-83, a novel KCNQ channel opener, by establishing and optimizing a 6 Hz corneal kinked model, and to provide a scientific basis for the application of QO-83 in drug-resistant epilepsy. METHODS The mice were divided into control group, model group, positive drug levetiracetam (100 mg·kg^-1) group, control drug carbamazepine (50 mg·kg^-1) group, and QO-83 low (2 mg·kg^-1), medium (4 mg·kg^-1), and high (6 mg·kg^-1) dose groups. The 6 Hz kindled mice were established, and drugs was injected intraperitoneally. After 30 min, 6 Hz corneal stimulation was applied again to observe its protective effect on the animal. And set up a series of behavioral experiments: tail suspension test, T-maze test, and new object recognition test, observe the immobility time, selection accuracy, and recognition index of mice respectively, to evaluate its impact on animal depressive tendencies and memory abilities. Immunofluorescence staining was performed on 6 Hz model mice to observe the expression changes of c-Fos protein and evaluate the protective effect of QO-83 on specific brain regions. Observe the expression changes of its target KCNQ2 protein and evaluate its impact on target protein expression. RESULTS The established model mice were not sensitive to the action of carbamazepine (50 mg·kg^-1), but effective against levetiracetam (100 mg·kg^-1). When given 2, 4 and 6 mg·kg^-1 QO-83, dose-dependent anti-epileptic effects can be observed, which significantly reduced the incidence and duration of seizures in ignited mice. The 4 mg·kg^-1 of QO-83 can significantly reduce the immobility time of epileptic mice in tail suspension experiments, increase the accuracy of mice in T-maze test, and increase the recognition index (RI) of mice in new object recognition test. QO-83 can significantly downregulate the expression of c-fos in the hippocampus and piriform cortex of epileptic mice, and upregulate the expression of KCNQ2 protein in the CA3, DG regions and their surrounding fibers and PIR regions of late-stage model mice. CONCLUSION Compound QO-83 has good anti drug-resistant epilepsy activity, and its protective effect on epileptic animals is better than the positive drug levetiracetam. At the same time, it also has the effect of improving the behavior of epileptic animals, demonstrating the therapeutic potential for drug-resistant epilepsy. The mechanism of action may be related to upregulating the expression of the target protein KCNQ2.

OBJECTIVE To prepare puerarin/daidzein porous nanocrystals using polyethyleneglycol (PEG)and chitosan(CS)as carrier aterialsand evaluate their physicochemical properties and in vitro characteristics. METHODS The drug loading rate and entrapment rate were used as indicators to optimize the prescription,and the insoluble drug puerarin-daidzein was encapsulated in the form of inclusion compound by two-step method β-CD-puerarin-daidzein-PEG-CS nanocrystals. The inclusion degree of puerarin-daidzein nanocrystals was determined by Fourier transform infrared spectroscopy, thermogravimetry, X-ray diffraction, scanning electron microscope, antioxidant and bacteriostatic tests to verify the feasibility of the preparation method. And investigate its drug release behavior in simulated gastrointestinal fluid and gastric environment, and fit the drug release model. RESULTS The inclusion compound prepared by saturated aqueous solution method was the best when the volume fraction of inclusion compound was 1.000% acetic acid. Its cumulative release rate is about 90%, drug loading and inclusion rate are (26.13±0.74)% and (78.39±2.23)%, respectively. Puerarin-daidzein nanocrystals have many and dense pore diameters, and have good antioxidant performance. Obvious inhibition zone against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa can be observed, showing good antibacterial performance. CONCLUSION Puerarin-Daidzein porous nanocrystals can significantly improve the dissolution of insoluble drug daidzein, which lays a foundation for its application in the field of biomedicine.

OBJECTIVE To prepare osthole(OST) nanocrystallization and evaluate its characterization. METHODS OST-NSs were prepared by a media grinding method, and the average particle size and polydispersity index (PDI) were used as indicators to optimize the formulation and process parameters. The crystal morphology, crystal form, and interaction between OST-NCs and stabilizers were characterized. Their surface wettability, equilibrium solubility, and in vitro dissolution in various media were investigated, and the f₂ value was used to evaluate the similarity of the dissolution curves. RESULTS The formulation and process parameters for preparing OST-NCs were as follows: OST (3%): PVP-VA64, sodium deoxycholate 25∶5∶1, the volume ratio of grinding beads (0.4-0.6 mm) to OST suspension was 2∶1, and it was ground at 450 r·min^-1 for 70 min, and 9% mannitol was used as a lyophilized protective agent to prepare OST-NCs. The stability of OST-NCs decreases with increasing temperature. After reconstitution, the particle size of OST-NCs was (354.2±9.857) nm, the PDI was (0.259±0.023), and the Zeta potential was (-22.2±0.896) mV. OST-NCs basically maintain the rod-shaped crystal structure. There is no interaction between OST and the stabilizer. The surface wettability of OST-NCs is better than that of OST and its physical mixture. The equilibrium solubility of OST-NCs in pure water is 231% that of OST. Among the six dissolution media, the dissolution rate and cumulative dissolution of OST-NCs were significantly better than those of OST and its physical mixture. Additionally, the f₂ values for the physical mixtures were greater than 50, whereas those for OST-NCs were less than 50, as compared with the dissolution curves of OST. CONCLUSION The results show that the reproducibility of OST-NCs is good during their preparation. The grinding temperature should be reduced, and the grinding time should be optimized. The dissolution behavior of OST-NCs is significantly different from that of OST. The reduction of particle size is the main reason for the improved water solubility of OST-NCs. These results suggest that the nanocrystallization strategy based on media grinding can effectively improve the water solubility and hydrophobicity of OST and has a good application prospect in the development of new OST drugs.

OBJECTIVE To establish an UHPLC-MS/MS method for the determination of six alkaloids in Tianma capsule. METHODS Phenomenex Kinetex C₁₈ (2.1 mm×100 mm, 2.6 μm) column was used for separation. The mobile phase consisted of methanol and 0.1% formic acid (containing 2.5 mmol·L^-1 ammonium acetate) solution (gradient elution). The flow rate was 0.3 mL·min^-1 and the column temperature was maintained at 35 ℃. Electrospray positive ion source was used for mass spectrometry detection by multiple reaction monitoring mode. RESULTS The liner range of calibration curve was 79.38-3 969 ng·mL^-1 (r=0.999 9), 18.60-929.8 ng·mL^-1 (r=0.999 8), 38.20-1 910 ng·mL^-1 (r=0.999 9), 1.264-252.8 ng·mL^-1(r=0.999 3), 1.196-239.2 ng·mL^-1(r=1.000 0) and 1.268-253.6 ng·mL^-1(r=1.000 0)for benzoylmesaconine, benzoylaconine, benzoylhypaconine, mesaconitine, hypaconitine and aconitine. The RSD of repeatability test (content) was 0.5%-3.2%. The average recoveries was in the range of 98.3%-105.3%. RSD was 1.0%-3.4%. CONCLUSION The method has good sprcificity, sensitivity and accuracy, and it is suitable for the analysis of six alkaloids in Tianma capsule.

OBJECTIVE To analyze the common pharmaceutical issues in application of generic nifedipine controlled-release tablets, in order to provide reference for the research and manufacture of this formulation. METHODS Based on some references and review experience, the common issues in the application documents of generic nifedipine controlled-release tablets about prescription research, production process research, and quality control, etc., were analyzed. RESULTS and CONCLUSION Nifedipine controlled-release tablets have certain technical difficulties and individual drug characteristics. A comprehensive study should be conducted on the basis of osmotic pump controlled-release technology, combined with the characteristics of the reference formulation and nifedipine controlled-release tablets, to ensure that the quality of the generic formulation is equivalent to that of the reference formulation.

OBJECTIVE To understand the overall situation of Tibetan medicines on the market, and to explore the method of comprehensive evaluation of Tibetan medicines. METHODS Data were extracted from the drug information network of the State Drug Administration and analyzed from the dimensions of manufacturers and varieties of Tibetan medicines. RESULTS The 373 items of proprietary Tibetan medicine were included, 80 items (proprietary Chinese medicine) were excluded, 19 manufacturers were involved, and 182 different dosage forms of proprietary Tibetan medicine were involved. The protection level of Tibetan patent medicine protection varieties includes 16 varieties, and the provincial standard document number involves 16 varieties. The classification of systemic treatment diseases is mainly concentrated in the treatment of gastrointestinal diseases, the treatment of skin, yellow water and rheumatic drugs, the treatment of liver diseases. CONCLUSION The preliminary comprehensive evaluation catalogue of proprietary Tibetan medicines can be conducted in steps according to the existing evaluation methods of proprietary Chinese medicines in terms of protected varieties, multi-varieties of manufacturers and classification of major diseases.The first batch of varieties include 25 Flavor Song shi pills, 25 Flavor Coral pills, 25 Flavor Pearl pills, 25 Flavor Guijiu pills, Zhituo Jiebai pills, 15 Flavor Black pills, 70 Flavor Pearl pills, Renqing Changjue, Coral 70 Flavor pills, Pain Relieving patch, and Nodikon capsules.

The use of traditional dressings, such as gauze, cotton and bandages, has been gradually reduced in medical practice due to their disadvantages, including poor permeability and the tendency to cause secondary injuries during replacement. In contrast, functional hydrogels have attracted much attention due to their excellent biocompatibility, high water retention, ease of introduction of functional components and accelerated wound healing. This paper describes the mechanisms of skin wound healing and the properties of different types of wound dressings. It summarizes the research progress in functional hydrogels constructed by physical or chemical crosslinking over the past five years. Additionally, it offers insights into the future development trends of functional hydrogels.

OBJECTIVE To investigate the safety of the tetravalent influenza vaccines adjuvanted with PEG6000 and cationic [2,3-dioleoxypropyltrimethylammonium chloride(DOTAP)∶1,2-dioleoyl phosphatidylcholine(DOPC)]-modified liposomes. METHODS Mice were divided into five groups∶ PBS negative control group, blank neutral liposome group, PEG6000 liposome group, cationic 4∶1 liposome group, and vaccine stock solution group. Abnormal toxicity test, acute toxicity test, and long-term toxicity test were performed. The general behavior, body weight, food intaking, viscera index, morphology, and blood indexes of mice were recorded to evaluate the safety of the vaccines adjuvanted with PEG6000 and cationic-modified liposomes. RESULTS Abnormal toxicity test∶ within 7 days after injection, all mice were alive with weight gaining and without abnormal symptoms. Acute toxicity test∶ 0.5 mL (hemagglutinin content 15 μg) was injected intraperitoneally, and no abnormal reaction or death was observed within 14 d. Long-term toxicity test∶ The mice were inoculated with 0.2 mL of hemagglutinin (6 μg) at 0, 14 and 28 d respectively. The mice were executed in the acute phase (3 d after the last immunization) and the recovery phase (14 d after the last immunization). No abnormal conditions and death were observed in the mice during the experiment period, and their body weight increased. Hematological examination and blood biochemical indexes fluctuated within the normal range, no toxic reaction related to drug administration was found, and no pathological changes were found in organs. CONCLUSION The tetravalent influenza vaccine adjuvanted with PEG6000 and cationic (DOTAP∶DOPC mole ratio 4∶1)-modified liposome has good safety.

OBJECTIVE To design and synthesize novel CDK9 inhibitors 1-(2-adamantan-1-yl-1H-indole-5-yl)-3-substituted thiourea derivatives and study their anti-gastric cancer activities. METHODS A series of target compounds 7a-7m were synthesized from adamantan formyl chloride by 6-step reactions. The structures of the target compounds were identified by ¹H-NMR, ¹³C-NMR, and HRMS. MTT assay was used to detect the inhibitory effect of synthetic compounds on the growth of gastric cancer cells, ADP-Glo kinase assay was used to detect the effect of synthetic compounds on CDK9 kinase activity and Western blot assay was used to detect the regulatory effect of hit compound on downstream signaling pathways. RESULTS The target compounds had certain inhibitory activity on the growth of gastric cancer cells, among which compound 7l had the best activity on the gastric cancer cell line (SGC-7901) with IC₅₀ value of (2.26±0.04) μmol·L^-1, and 7l had little toxicity on normal gastric epithelial cells (IC₅₀ >100 μmol·L^-1). In addition, 7l showed specific inhibitory effect on CDK9 kinase activity in vitro. Upon 1 μmol·L^-1 7l treatment, CDK9 kinase activity was only (21.67±1.47)%, and in gastric cancer cells 7l inhibited CDK9 downstream protein p-ser2 expression in a concentration-dependent manner. Finally, molecular docking study showed that 7l could stably bind to the active site of CDK9 and had a high binding affinity. CONCLUSION This series of compounds have good anti-gastric cancer activity and are worth of further study.