OBJECTIVE To explore the extraction conditions for elemental impurities in metal containers used for drug packaging. METHODS Different extraction conditions were set, and the metal containers used for packaging 6 types of drugs were extracted separately. The content of the extracted elements was determined using inductively coupled plasma mass spectrometry. RESULTS When 4% acetic acid is used as the extraction medium, more impurities of elements are released from various containers. When using water as the extraction medium, the amount of As, Cd, Pb, V, Co, Ni, Cr, and Cu elements dissolved from various containers is basically the same when extracted at (121±2) ℃, held for 30 min or (70±2) ℃, and held for 24 h. For Mg, Al, Mn, Fe, and Zn elements, the extraction amount obtained by organic inner coating containers under two extraction conditions is basically the same. Containers with anodized and plasma sprayed inner walls, as well as bare metal containers, can leach more elements except for Mg at (121±2) ℃ for 30 min of insulation. CONCLUSION When determining elemental impurities in metal containers for drug packaging, 4% acetic acid can be selected as the extraction medium with stricter control. By water extraction at (70±2) ℃ and insulation for 24 h, it can meet the determination requirements of Class 1, Class 2A, and Class 3 elements in ICH-Q3D.

Traditional Chinese medicine (TCM) decoction is a complex dispersion system, and its active components are mostly to form different phases in the form of solutes or dispersed substances, such as true solution, colloidal phase, suspension phase, etc. The active components are complex and diverse, and the formation, transformation, and transmission of each phase may affect the metabolism and action process of the pharmacodynamic components in biological bodies. However, the study on the phase differences and effective phases in TCM decoction is still in the initial stage. In this paper, we will be explored the quality basis and mechanism of TCM decoction from the perspectives of the formation, characterization, transformation, transmission and mechanism of the ordered phase in TCM decoction, and look forward to the quality research mode of TCM based on phase structure, so as to provide a reference for explaining the effect mechanism of TCM decoction from the perspective of structural TCM decoction.

OBJECTIVE To evaluate the preclinical safety of chimeric antigen receptor T (CAR-T) cell U87 in tumor-bearing immunodeficient mice. METHODS A transplantation tumor model was constructed using NCG mice subcutaneously inoculated with BxPC-3, on which cells U87 (2×10⁶cells each mouse and 10×10⁶ cells each mouse) were administered in a single dose, and continued to be observed until day 84 after administration. Tumor clearance, survival rate, clinical symptoms, body weight changes, hematological indices, lymphocyte subpopulation classification, cytokine indices, and histopathological changes were examined to characterize the mice. RESULTS Single tail vein administration of U87 to hormonal NCG mice significantly prolonged mouse survival and even completely cleared the tumor load. As its pharmacodynamic action, U87 resulted in elevated levels of human-derived IFN-γ, as well as mixed cell aggregation in multiple tissues/organisms, with no local irritation and no apparent systemic toxicity associated with U87. U87 led excessive immune response at high doses, and has certain effects on the values of GLU, TG, TP, ALB, PLT and RET in animals. Mild GvHD-associated histopathological changes were only observed in 2×10⁶ CAR-T (from week 8 after cell administration) and 10×10⁶ CAR-T (from week 4 after cell administration), and the changes correlated with the level of T-cell proliferation. No tumor formation associated with U87 was seen. CONCLUSION U87 does not show any significant risk associated with immunotoxicity and tumorigenicity in BxPC-3 loaded NCG mice and shows some pharmacodynamic effects. The results of this study provide implications for the toxicological evaluation of targeted solid tumors.

OBJECTIVE To prepare and characterize scoprone-loaded PLGA microspheres. METHODS Scoprone-loaded PLGA microspheres were constructed by a O/W emulsion-solvent evaporation method.Their surface morphology, encapsulation rate and drug loading of microspheres were the main evaluation indexes. Based on single factor experiment,the optimum preparation conditions of PLGA microspheres were obtained through central composite design. RESULTS Scoprone-loaded PLGA microspheres were light yellow powder and spherical in shape with smooth surface with size 2.94 μm.Scoprone was loaded into PLGA microspheres with drug loading(4.28%)and encapsulation efficiency(47.03%). CONCLUSION Scoprone-loaded PLGA microspheres are constructed successfully. The particle size of microspheres meets the requirements of intraocular vitreous cavity injection, and has good slow-release performance under simulated in vitro environment. The preparation method is accurate and reliable, and can provide a new dosage form for the treatment of diabetic retinopathy.

OBJECTIVE To prepare liposome formulations encapsulating isovaleryl shikonin, to optimise the preparation process. METHODS The isovalerylshikonin-liposome (IsoSHK-lip) were prepared by the thin film dispersion method. The UV absorption, standard curve, precision, stability and recovery of IsoSHK-lip were investigated. A response surface optimization method was used to optimize a 3-factor, 3-level preparation scheme with A: lecithin-cholesterol mass ratio, B: lecithin-isovalerylshikonin mass ratio and C: volume of hydrated solvent as the three factors. The particle size, polymer dispersity index (PDI), Zeta potential, morphological characterisation and stability of IsoSHK-lip were also investigated for the optimal solution. RESULTS The response surface optimization predicted that the optimal preparation conditions for IsoSHK-lip were: lecithin-cholesterol mass ratio of 8.82∶1, lecithin-isovalerylshikonin mass ratio of 30.65∶1, and volume of hydrated solvent of 29.22 mL. Repeated preparation of the optimal IsoSHK-lip resulted in an average encapsulation rate of 90.03%, a mean particle size of 117.48 nm, a mean PDI of 0.246, and a mean Zeta potential of -13.59 mV. The stability experiments showed that the particle size, PDI and Zeta potential of IsoSHK-lip did not change significantly after 7 d at 4 ℃. Transmission electron microscopy showed that the IsoSHK-lip was subspherical with particle sizes in the range of 100-200 nm. CONCLUSION IsoSHK-lip is prepared by repeating the optimal results obtained by response surface methodology three times, resulting in a near spherical shape, smaller particle size, uniform particle size distribution and better stability of IsoSHK-lip, which provides the basis for subsequent pharmacological studies of dosage forms.

OBJECTIVE To establish content determination method of polyethylene glycol (PEG) in mupirocin ointment. METHODS The content determination method of PEG was performed on TSKgel G2000SW_XL column at 35 ℃ using refractive index detector at 35 ℃, 0.1 mol·L^-1 NaNO₃(pH 3.0) was used as mobile phase and the flow rate was 1.0 mL·min^-1,and the injection volume was 20 μL. RESULTS The content determination method of three different PEG in mupirocin ointment was established. The type and content of PEG in mupirocin ointment from different manufacturers were determined. In this method, the limits of detection (LOD) for PEG400, PEG3350, and PEG4000 were all 0.01 mg·mL^-1. The limits of quantitation(LOQ) were all 0.02 mg·mL^-1, and the ranges of linearity were all 0.2 to 5.0 mg·mL^-1. The average recoveries were 99.3%、99.8% and 100.2%, respectively (n=3). CONCLUSION The established method is efficient, rapid, accurate and sensitive, which can be used as the content determination method of PEG in mupirocin ointment.

OBJECTIVE To investigate the terpenoid constituents from the fresh-used leaves of Artemisia argyi Levl. et Vant. and their anti-inflammatory activities. METHODS Modern phytochemical separation techniques such as high performance preparative liquid chromatography (HPLC) were used to isolate the 95% ethanol extract of the fresh leaves from A. argyi and to identify the structure by combining physicochemical properties with MS and NMR data. The anti-inflammatory activity of terpenoids was evaluated by the inhibitory ability of nitric oxide (NO) release from LPS-induced RAW264.7 macrophages. RESULTS Fifteen terpenoids were isolated from the fresh leaves of A. argyi and identified as artanomaloide (1), dehydroleucodin (2), tamaulipin-B acetate (3), moxartenolide (4), yomogin (5), costic acid (6), costic acid methyl ester(7), PBI(8), (-)-3-hydroxy-β-ionone(9), pubinernoid A(10), subamone(11), artefrigin(12), cassipourol(13), 3β-acetoxy-24-oxo-dammara-20, 25-diene (14), dammara-20,24-dien-3β-ol acetate (15). The IC₅₀ values of the anti-inflammatory activity of compounds 1-12 ranged from (1.27±0.02) to (17.55±0.13) μmol·L^-1. CONCLUSION The fresh leaves from A. argyi are more abundant in terpenoids with anti-inflammatory activity, among which compounds 3 and 7-14 are isolated for the first time, and this kind of components can be applied in the development of pharmaceutical and health products.

OBJECTIVE To investigate and analyze the quality status of lysozyme oral preparations, and study the key quality control technologies for common problems in current standards, so as to provide technical support for drug supervision. METHODS The 28 batches of lysozyme lozenges and 47 batches of lysozyme enteric-coated tablets obtained by medicine post market quality surveillance were tested according to the current legal standards, and several analytical methods were established for exploratory research. RESULTS According to the legal standard test, although the qualified rate of 75 batches of lysozyme oral preparations was 100%, it was still found that there were problems in the legal standard such as the potency determination has significant errors and lacks key quality control items such as dissolution and content uniformity. The results of exploratory study on potency differed greatly from those of statutory test, the results of dissolution study showed that some enteric-coated tablets were not easy to dissolve, and the results of content uniformity study showed that some large size enteric-coated tablets did not meet the requirements. CONCLUSION As a traditional biological extraction type of biochemical drugs, lysozyme oral preparations are marketed early, so some quality standards can no longer reflect the current situation of the products. The enterprises should optimize the production processes and improve current standards.

OBJECTIVE To prepare cepharanthine(CEP) polymer micelles and characterize them. METHODS The CEP polymer micelles were prepared by solvent evaporation method. Based on the single factor investigation, the preparation process was optimized by Box-Behnken response surface method with the entrapment efficiency and drug loading as indicators, and the particle size distribution, potential and in vitro release of the micelles were characterized. RESULTS The optimum process of CEP polymer micelle was as follows: 50 mg of MA-PEG-PLGA and 17.82 mg of CEP were dissolved in 0.25 mL of acetone, added dropwise into 14 mL of PBS solution at 60 ℃ and stirred on a magnetic stirrer at a speed of 1 000 r·min^-1 for 4 hours to obtain a clear CEP polymer micelle. The optimized CEP polymer micelles are spherical, with an average particle size of (111.37±3.51) nm, a PDI of (0.21±0.01) and a Zeta potential of (-9.78±2.15) mV. In vitro release results showed that CEP was released rapidly within 10 h, and its micelles released (79.99±4.96)% and (71.66±2.62)% respectively within 72 h, indicating that CEP could be released slowly after being made into micelles. The results of freeze-drying agent investigation showed that 0.5% poloxamer 188 had the smallest change in complex particle size after freeze-drying. The results of hemolysis test showed that the hemolysis rate was obviously reduced after CEP was made into micelles. CONCLUSION The optimized formulation and technology in this study can be used for the preparation of CEP-MA-PEG-PLGA polymer micelles, which lays a foundation for the subsequent development of CEP targeted preparations.

Triptolide (TP), also known as triptolide alcohol, is an epoxidised diterpene lactone compound extracted from the xylem of Tripterygium wilfordii Hook. f., a plant of the Weseraceae family. As the main active ingredient in Tripterygium wilfordii Hook. f. extracts, it has been proved to have immunosuppression, anti-tumor, anti-inflammation and other pharmacological effects. However, the development of triptolide has been limited due to its poor water solubility, high toxicity, obvious adverse reactions and low bioavailability. Therefore, researchers have optimised the structure of triptolide with the hope to improve its physicochemical properties. By now, the structure optimization has mainly been focused on sites like C-5,6, C-14, C-16, C-20, epoxy groups, unsaturated five-membered lactone ring. This paper summarizes the researches related to the structure optimization and their biological activity of the above reactive sites, which provides new thoughts for the structure-activity relationship and clinical application of triptolide.