Low-concentration atropine eyedrops, an ophthalmic formulation for delaying myopia of adolescents, has been widely recognized due to its clinical therapeutic effects. However, the commercialized atropine sulfate eyedrops, ophthalmic aqueous solution, have many problems, such as eye irritation caused by low pH value of the aqueous solution, poor stability of the preparations and poor patient compliance. In this review, the formulations and preparation processes of atropine sulfate ophthalmic preparations currently under development and on the market are summarized, the characteristics, advantages and disadvantages of various technical approaches for improving stability and compliance of atropine sulfate ophthalmic products are analyzed, hoping to provide some references for the optimization of atropine ophthalmic formulations.

Based on the six major systems of drug production quality management and the analysis of the typical production processes of chimeric antigen receptor T cell(CAR-T) products, this review analyzes and discusses the particularity of the CAR-T product production system and the corresponding key quality management points from four main aspects, namely product production process quality control, process validation and aseptic processing simulation test, contamination and cross contamination control in the production process, and production related deviation and change control. This review provides some references to cell therapy product manufacturers especially CAR-T product manufacturers, to further improve production system quality management, and also provides a reference to production inspection and quality audit.

Doxorubicin is one of the potent drugs in the clinic for the treatment of blood cancers and solid tumors. However, side effects and drug resistance of doxorubicin pose major obstacles to its application in antitumor therapy. Curcumin exhibits multiple pharmacological effects such as antitumor activity, antioxidation, and anti-inflammation. When combined with doxorubicin, curcumin can enhance efficacy, reduce toxicity, and reverse multidrug resistance. Nevertheless, due to the poor solubility, instability, and low bioavailability of curcumin, the application of this combination therapy is limited. Currently, the nano drug co-delivery system offers numerous advantages in antitumor therapy. A nano-based co-loading delivery system of curcumin and doxorubicin can improve drug solubility, enhance stability, achieve targeted drug aggregation, and realize sustained- and controlled- release at the tumor site. This review summarizes the antitumor mechanisms of the concomitant use of curcumin and doxorubicin and their novel nano-based drug delivery systems in recent years, providing ideas for further research on this combination therapy and the development and application of their nano-formulations.

Mesoporous silica nanoparticles(MSNs) have adjustable pore diameters and pore structures, high specific surface areas, as well as good biocompatibility. As a delivery carrier, MSNs can enhance drug stability, realize the controlled release of drugs, and improve the solubility and bioavailability of poorly soluble drugs. This review summarizes the advantages of MSNs as drug carriers, introduces the applications of MSNs in drug delivery and disease treatment in recent years, and anticipates the application prospects of MSNs.

A novel synthetic route for the preparation of the camptothecin intermediate, the racemic lactone(17), starting from 6-chloro-2-methoxynicotinic acid(12) was reported in this paper. Initially, compound 12 underwent a nucleophilic addition reaction with the selected 1-(tert-butyldimethylsilyloxy)butan-2-one. Employing an acetal and a benzyl group for selective protection, the synthesis proceeded through oxidation, deprotection and cyclization with methylsulfonic acid. The overall yield of this process was 31.23 ％ (based on 12). Compound 17 could be effectively converted into the racemic tricyclic ketone through four additional steps. This new synthetic method successfully avoided the needs for hazardous reagents such as ozone, osmium tetroxide, and cyanides, greatly enhanced the safety.

Finerenone(1) was synthesized from diketene and 4-methoxybenzylamine as the starting materials, through the aminolysis, condensation, Hantzsch cyclization, ethylation, and chiral resolution steps. After optimizing the reaction conditions, the overall yield of this process was 11.4％ with the purity of 99.7％ . The usage of 4-methoxybenzyl group as the protection group was reported at the first time in this route, which was suitable for industrial production.

A green and efficient synthetic method of non-steroidal anti-inflammatory drug celecoxib(1) was reported in this paper. With p-methylacetophenone(2) and ethyl trifluoroacetate(3) as starting materials, the Claisen condensation was performed with potassium carbonate(98 nm) instead of sodium ethoxide by “one-pot method”. After the Claisen condensation and filtration, the filtrate without purification was cyclized with 4-hydrazinobenzene-1-sulfonamide hydrochloride(5) to obtain the target product 1. The total yield of celecoxib was 86.8％ with HPLC purity of 99.65％ . The alkali could be recovered by filtration and calcination, and its reuse had little effect on the yield. This green synthetic method has mild conditions, simple operation, short reaction period, good economy, high yield and less environmental pollution, which is suitable for industrial production.

CD16 has the capacity to effectively mediate natural killer(NK) cell activation without the necessity for co-engagement of other receptors, making it a widely selected target in bispecific antibodies(BsAbs) based on NK cell redirection. Mesothelin(MSLN) is significantly overexpressed in various solid tumors and can promote tumor cell adhesion, migration, proliferation, and survival. In this study, a bispecific antibody, 16MSLN, targeting both CD16 and MSLN was constructed. The antibody was expressed in Expi293F cells and purified using Protein L to obtain highly pure target antibody. The results of cell experiments indicated that 16MSLN could promote the crosslinking of NK cells with target cells and specifically enhance the killing effect of NK cells on MSLN+ tumor cells. This study provides a reference for the development of NK cell-redirected BsAbs.

The ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) method was established to study the prototypical components and metabolites of Lycii Fructus extract in serum, urine, faeces, and bile of rats and to clarify their metabolic processes. The Waters ACQUITY UPLC BEH C18 column(2.1 mm×50 mm, 1.7 μm) was used, and the analysis was carried out in the gradient elution mode with acetonitrile as mobile phase A, and 0.1％ formic acid as mobile phase B. The column temperature was 30 ℃ , the flow rate was 0.3 mL/min, and the injection volume was 3 μL. The results showed that a total of 46 chemical components were identified from various biological samples, including 17 prototypical components and 29 metabolites. Its metabolic pathways included phase Ⅰmetabolic reactions(hydroxylation, dehydroxylation, demethylation, hydrolysis, and reduction) and phase Ⅱ metabolic reactions(methylation, glucuronidation, sulfation, and sulfonation). This study preliminarily elucidated the metabolic process of Lycii Fructus in vivo, and laid a foundation for the subsequent elucidation of its pharmacological material basis and development.

An HPLC method was established for the determination and quantification of 5 representative compounds, namely chlorogenic acid, caffeic acid, 4,5-dicaffeoylquinic acid, 1,3,4-tricaffeoylquinic acid and luteolin, in the resin separation processes. The optimal resin was selected by the static and dynamic adsorption/desorption experiments. Process optimization of packed column separation was conducted. A UPLC method was also established for the determination and quantification of 10 representative compounds, e.g., chlorogenic acid, caffeic acid, caffeoylquinic acids and flavonoids, in alkali precipitation processes. The purities and recovery ratios of active compounds were determined to optimize the alkali precipitation process parameters, including solvent type, solvent addition sequence, material-liquid ratio and amount of alkali. The results showed that LS305 resin had better adsorption and desorption capacities for the five components. The majority of impurities could be washed by 0.5 ％ formic acid, which could remove about 82 ％ of impurities and solids. The efficient separation of active compounds could be achieved by 60％aqueous ethanol. The alkali precipitation was carried out with ethyl acetate-ethanol(4 ∶ 1) as the precipitant in a material-liquid ratio of 100 mg ∶ 1 mL. Then, 0.15％ ammonia was added. After filtration and evaporation, the novel extract of Gnaphalium affine was obtained with the total contents(mass fraction) of 10 compounds more than 50％ .

Limonene-loaded dipalmitoyl phosphatidylglycerol(DPPG) anionic long cycle liposomes were constructed by ethanol injection, and the formulation of the liposomes were optimized with particle size and PDI as the evaluation indexes. The results showed that the optimal liposomes were prepared in a 46.5 ∶ 10 ∶ 38.5 ∶ 5 molar ratio of hydrogenated soybean phospholipid, DPPG, N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-snglycerol- 3-phosphoethanolamine sodium and cholesterol. The particle size and PDI of the optimized liposomes were (62.84±2.36)nm and 0.241±0.012, respectively. Moreover, the products appeared spherical with relatively uniform distribution and obvious phospholipid bilayer structure in the TEM images. The serum stability and blood compatibility of the drug-loaded anionic liposomes were good and could be stably stored at 4 ℃ for 4 d. The cumulative release rate within the first 12 h in PBS was about 50 ％ , and was about 80 ％ at 48 h, showing a slow release characteristics. Pharmacodynamic studies in mouse models showed that the limonene anionic liposomes could improve the enlargement of gallbladder size, bile turbidity and gallstones in cholesterolosis mice, and also inhibit the inflammation in liver and gallbladder sites.

Based on the principle that uricase catalyzes the decomposition of uric acid to produce allantoin, hydrogen peroxide and carbon dioxide, this paper established a method to detect the activity of uricase at 37 ℃ and pH 7.5. The results showed that the quantitative ranges of hydrogen peroxide and uricase were 0.049 - 100.000 μmol/L and 0.819 - 200.000 mU/mL, respectively. The within- and between-run variation coefficients of precision were less than 20.0％ , and the relative error of accuracy were within ±25.0％ . The results of recovery experiments using hyperlipemia samples(lipid index 3 mg/mL) and 2％ hemolysis donor samples compared to normal donor samples showed that hyperlipemia did not interfere with the detection of uricase activity, whereas hemolysis did. Uricase activity was not affected when human serum uricase samples were placed at room temperature or 2 - 8 ℃ for no more than 24 h, frozen and thawing for no more than 3 cycles, and stored at –70 –90 ℃ for no more than 64 days. In conclusion, the established method is sensitive, precise, accurate, simple, rapid, and can support the evaluation of preclinical and clinical studies of uricase drugs.

An ion-pair reversed phase high performance liquid chromatography method was established for the determination of the process impurities and degradation products in faropenem sodium(1). The Welch Xtimate C18 column(4.6 mm×150 mm, 3 μm) was used, and the analysis was carried out in the gradient elution mode with phosphate buffer(pH 3.0) as mobile phase A, and phosphate buffer-acetonitrile(50 ∶ 50) as mobile phase B. The flow rate was 1.0 mL/min, the column temperature was 25 ℃ , and the injection volume was 20 μL. The results showed that the peaks of 1 and its related impurities were separated well, and it was linear for 1 and the related impurities in the corresponding ranges. The average recoveries(n=9) of the impurities were 96.35％ - 104.28％ , with the RSDs of 1.38 ％ - 4.25 ％ . The established method has high accuracy, sensitivity, specificity, and repeatability, which is suitable for the determination of process impurities and degradation products in 1.

A gas chromatography-mass spectrometry(GC-MS) method was established for two genotoxic alkyl chloride impurities, namely 4-chloro-4-methylpentan-2-one(2) and 2,6-dichloro-2,6-dimethyl-4-heptanone(3), in cetirizine dihydrochloride(1). The VF-WAXms capillary column(0.25 mm×30 m×0.25 μm) was used, and the measurement was performed in selected ion monitoring(SIM) mode. The results showed that it was linear for 2 and 3 in the ranges of 75.86 - 455.16 ng/mL and 75.18 - 451.08 ng/mL. The limits of quantification were 0.025 and 0.066 ng/mL, respectively. Tthe recoveries were 101.66％ and 102.46％ , respectively. The established method can determine 2 and 3 in 1, which provide a reference for the quality study of 1.

An ICP-MS method was established for the determination of elemental impurities, namely Cd, Pb, As, Hg, Co, V, Ni, Li, Sb, Cu in tert-butanol. The microwave digestion method was used, and the sample was digested with a nitric acid-hydrochloric acid mixed solution. After eliminating matrix interference and instrument drift through online internal standards, the measurement was carried out. The results showed that the quantification limits of Cd, Pb, As, Hg, Co, V, Ni, Li, Sb, and Cu were 0.028 8, 0.179 8, 0.057 6, 0.229 4, 0.015 3, 0.025 3, 0.232 2, 1.226 0, 0.021 9, and 0.138 6 ng/mL, respectively, all of which were less than 5 ％ of the limit values and met the detection requirements. The RSDs of repeatability and precision were both less than 20％ . Within 25％ to 300％ of the limit concentration range, it was linear for the ten elemental impurities, with recovery rates ranging from 90％ to 120％ . The established ICP-MS method is convenient, fast, highly sensitive, and accurate, which provide a technical support for the quality control research of tert-butanol.