随着全球医疗需求增长及环保意识增强，传统化学制药的高污染、高能耗等问题日益凸显。为实现可持续发展，该 文结合绿色化学理念，提出“绿色化学制药十二原则”，旨在通过技术创新与工艺优化，降低环境负担并提升资源效率。该 原则涵盖合成路径设计、能源经济性、可再生原料使用、催化反应优化、溶剂选择、智能化生产等关键环节，强调利用人 工智能技术实现工艺精准控制与流程强化。同时，倡导副产物资源化、连续化生产和药物递释系统理性设计，以减少废弃 物排放并提高药品质量。该原则不仅为制药工艺研发与生产提供指导，还将推动行业标准的制定，促进制药工业向绿色、 高效方向转型，为全球药品需求的战略满足提供科学支撑。

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.

Covalent organic frameworks(COFs) have attracted great attention in the field of drug delivery due to their characteristics such as high specific surface area, uniform and adjustable pore size, and facile modification and functionalization. This review introduces the preparation methods of COFs, including template-mediated coprecipitation method, one-pot synthesis method and in situ doping method. More over, this review elaborates the structural design of COFs, including intelligent stimuli-responsive molecular design and surface modification. In addition, this review also outlines the applications of COFs in the field of delivery of antineoplastic, antibacterial and anti-inflammatory drugs, aiming to provide insightful perspectives to facilitate the rapid development of COFs-based drug delivery systems.

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.

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.

Deuterium substitution is a method that involves replacing specific hydrogen(H) atoms in drug molecules with deuterium(D) atoms, thereby improving the absorption, distribution, metabolism, and affecting of the drug molecules within the body. It can reduce the dosage or frequency of administration, enhance safety, and achieve better therapeutic outcomes. Nowadays, deuterium substitution has become an important strategy in rational drug design and optimization of druggability. The methods of deuterated modification primarily include chemical synthesis and enzymatic catalysis. Chemical synthesis encompasses techniques such as the introduction of deuterated intermediates, halogen or unsaturated bond reduction, acid/base catalysis, and metal-catalyzed hydrogen-deuterium exchange. Enzymatic catalysis involves methods such as enzyme-catalyzed hydrogen-deuterium exchange, reductive deuteration, and decarboxylative deuteration. This review outlines the latest research progress of drug molecule deuteration in recent years with the aim of providing references for the research and development of deuterated drugs.

化学仿制药质量和疗效一致性评价和国家组织药品集中带量采购的常态化推行，有助于提高药品可及性、降低医疗 成本、保障药品供应，促进医药行业朝着更加规范、高效、健康的方向发展。该文对仿制药一致性评价的进展情况、过评 品种的市场情况与纳入集中带量采购情况，以及对制药产业的影响等方面进行了系统分析，旨在为仿制药的产业研究提供 相关参考与借鉴。

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.

The continuous proliferation of viral products, such as viral vector vaccines, CAR-T products produced by lentiviral transduction, and adenovirus-based gene therapy products, has presented novel challenges for manufacturing units and regulatory agencies in terms of quality control and supervision due to the complexity of production methods and diversity of products. To ensure the purity, activity, and other quality attributes of viral products, it is imperative to conduct inspections during the production and release processes. The infectious titer, as one of the key quality attributes, holds significant importance as it allows for the evaluation of safety and efficacy. This review provides a comprehensive summary of the principles and applications of existing methods for quantifying virus infectivity, including plaque assay, 50％ tissue culture infectious dose, fluorescent focus assay, various polymerase chain reactions, flow cytometry, and nano-flow cytometry(nFCM). By introducing and comparing these methods, manufacturing companies and regulatory agencies can make informed decisions regarding the selection of appropriate techniques to ensure product quality in different application scenarios.

Peptide-drug conjugates(PDCs) are emerging targeted drugs, composed of payloads, linkers, and homing peptides. By homing peptides, cytotoxic molecules or radionuclides can be enriched in cells of diseased tissues, thereby reducing the toxicity to normal cells. With the advantages of high selectivity, high tissue penetration, and low immunogenicity, PDCs have become a hot spot in the development of a new generation of targeted antineoplastic drugs following antibody-drug conjugates(ADCs). Nevertheless, PDCs still face some challenges, such as poor in vivo stability, and low receptor affinity. This paper reviews the composition, clinical application progress, key technologies, and challenges of PDCs, aiming to provide some references for the development and application of PDCs.

注射剂为临床常用的高风险剂型，特别是小容量注射剂，其灌装量对临床用药的安全性和有效性至关重要。该文结 合各国法规、指南，对小容量注射剂过量灌装的确定方法进行分析和讨论，并通过举例说明过量灌装限度确定需要考虑的 因素，以期为探索合理的、符合技术及法规要求的研究策略提供参考。

In this study, a novel synthetic process of finerenone(1), an anti-diabetic nephropathy drug, was developed. Using 2-hydroxyethyl methyl sulfone(20) and 2,2,6-trimethyl-4H-1,3-dioxin-4-one(21) as starting materials, the target product 1 was synthesized through sequential steps including alcoholysis, Knoevenagel condensation, Hantzsch cyclization, etherification, chiral resolution, β-elimination, and ammonolysis, with an overall yield of 19.9％ (based on 20), purity of 99.80％ , and ee value of 99.82％ . The novel process features mild reaction conditions and well-controlled quality, yielding intermediate 2-(methylsulfonyl)ethyl (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro- 1,6-naphthyridine-3-carboxylate with high optical purity following resolution, making it suitable for industrial production.

In this paper, the synthetic route of phenylephrine hydrochloride(1) was improved. 3-Hydroxyacetophenone( 2) was used as the starting material to synthesize 2-chloro-1-(3-hydroxyphenyl)ethan-1-one(3) by reacting with sulfonyl chloride. Compound 3 was transformed into 1-(3-hydroxyphenyl)-2-[benzyl(methyl)amino]ethan-1-one(4) through nucleophilic substitution with N-methylbenzylamine. (R)-3-[2-[Benzyl(methyl)amino]-1-hydroxyethyl]phenol(5) was stereoselectively synthesized from 4 via reduction by the engineered bacteria containing carbonyl reductase A12. Compound 1 was obtained from 5 with the purity of 99.9％ and ee value of up to 99.9％ by palladium carbon debenzylation and salification, and the total yield reached to 62.8％ (based on 2). The improved synthetic route had the characteristics of simple operation and high yield, which was suitable for industrial production.

Diseases caused by bacterial infections pose a significant threat to human health. In recent years, the overuse of antibiotics has led to the emergence of drug-resistant microorganisms and the development of new bacterial strains. These factors have further exacerbated the threat of bacteria to human health and environmental safety. Consequently, the development of novel antibacterial materials to prevent the emergence of “superbugs” has become a key research focus. Metal-organic framework materials(MOFs) have emerged as star materials in the antibacterial field, owing to their exceptional crystallinity, high porosity, large specific surface area, and facile tunability through modification. However, traditional MOFs also exhibit some shortcomings, such as poor hydrophilicity, long antibacterial cycles, and lack of targeting. To overcome these drawbacks, post-synthetic modification of conventional MOFs has emerged as an important strategy. Based on this, this article summarizes several design approaches for novel MOF-based antimicrobial materials, including modification of MOFs metal nodes, functionalization of organic ligands, surface and pore structure modification, and the formation of composites with other materials. The aim is to provide a reference for the future synthesis of advanced antimicrobial MOFs.

药品上市后变更管理属于药品全生命周期管理的一部分，本文梳理了药品上市许可有关稳定性的要求及相关指导原 则，并对药品上市后有关变更事项中的稳定性要求及有效期确定进行分析。重点关注了稳定性研究中的放样条件选择、考 察指标制定和结果评价等方面的内容，对药品上市后变更稳定性研究中常见问题，结合审评实践进行了探讨，旨在为上市 后变更稳定性研究工作提供更多参考。

Droplet-based microfluidic technology shows great application potential in the preparation of drug delivery systems due to its excellent handling of fluids at the micro- or nano-scale. Compared with the microspheres prepared by conventional preparation methods, the microspheres prepared by droplet-based microfluidics exhibit a welldefined and controllable composition and structure, high monodispersity, and good process reproducibility. Focusing on the droplet generation passive method and passive microchannel device, this review introduces the basic principles of microsphere preparation by droplet -based microfluidics, and systematically analyzes the main effects of fluid-related parameters, device design parameters and additives on the critical quality attributes, including microsphere morphology, particle size distribution, encapsulation efficiency, and drug release behavior. It is hoped that this review can provide a reference for the research and development of microspheres.

The treatment for arthritis often involves long-term oral administration or intra-articular injection of nonsteroidal anti-inflammatory drugs to alleviate inflammation and slow down the progression of the disease. However, these treatments may give rise to gastrointestinal irritation, hepatotoxicity, intra-articular infections, and other adverse effects. As a transdermal drug delivery system, microneedles can penetrate the stratum corneum barrier to deliver drugs to the deeper epidermis and dermis layer rich in immune cells, and has attracted widespread attention and application in the field of arthritis treatment due to its advantages of minimally invasive and improved drug permeability. This review elaborates on the progress of microneedles in the treatment of arthritis, in order to provide a reference for the development of preparations for arthritis treatment.

国务院于2019 年启动针对高值医用耗材的治理改革，对高值医用耗材的价格形成、医保支付、市场监管和医疗行为 等方面进行联动治理和综合性改革。高值医用耗材的定义是否需要调整，已成为当前亟须探讨的问题。基于高值医用耗材 的历年政策及现状，该文对其定义进行梳理，探讨集采降价后其是否符合“有较高价格”的说法，并从价格和价值两大角 度重新界定。研究结果显示，在当前集采背景下高值医用耗材的定义与内涵应包括2 个方面：一是价格高，二是价值高( 满 足医学、技术和社会3 个特性维度之一)。符合上述2 个方面中任一方面的医用耗材即可称为高值医用耗材。

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.

In 2024, FDA approved 50 new drugs, including 31 chemical small molecules and 19 biological products. This review describes the descriptions, indications, mechanism of action, dosage forms and strengths, adverse reactions, and synthesis routes of all the small molecules, and the basic information about biological products.

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.

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.

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.

To determine the influence of different high inoculation densities on the expression level and quality of bispecific antibodies and strengthen the cell culture process, bispecific antibody cells were inoculated into a 3 L bioreactor at low, medium and high grades of high inoculation density[containing (10±1)×10 6, (15±1)×10 6 and (20±1)× 10 6 cells per 1 mL, respectively] for fed-batch culture. The influences of different inoculation densities on antibody expression level and quality were evaluated. The results showed that compared with low grade of high inoculation density, the antibody expression levels of the intensified medium or high grade of high inoculation density process increased to 1.43 g/L, and there was no significant difference in antibody quality. Within the same culture period(16 d), on the premise of no influence on antibody quality and reduction of costs, medium grade of high inoculation density should be adopted for inoculation density, and the antibody expression level could be increased to 1.43 g/L, which was an 81％ increase compared with the conventional process(0.79 g/L). Subsequently, the intensified medium grade of high inoculation density process was successfully scaled up to a 30 L bioreactor, providing valuable experience for subsequent antibody process development.

A HPLC-UV method was established to determine 15 related substances in tedizolide phosphate(1) bulk drug. The Welch Ultimate XBridge C18 chromatography column was used, and the analysis was carried out in the gradient elution mode with 0.01 mol/L ammonium dihydrogen phosphate and 0.01 mol/L ammonium dihydrogen phosphate aqueous solution(pH 5.5) as mobile phase A, and acetonitrile as mobile phase B. The detection wavelength was 235 nm. And another HPLC-UV method was established to determine the isomer impurity in 1 bulk drugs. The Daicel Chiralpak OJ-H chromatographic column was used, and the analysis was carried out with an isocratic elution mobile phase composed of n-hexane, ethanol and diethylamine in a volume ratio of 35 ∶ 65 ∶ 0.1. The detection wavelength was 300 nm. The results showed that it was linear for the relevant substances in the concentration range of 0.2 - 7.0 μg/mL, and the method recovery rate was 90％ - 108％ . The established method has good sensitivity, strong selectivity, and high repeatability, which can provide a reference for quality control research in 1.

The synthesis process of the antihyperglycemic drug linagliptin(1) was optimized, and the key process parameters for each step were determined, along with the impurities generated. Starting from 8-bromo-7-(but- 2-yn-1-yl)-3-methylxanthine(3), crude 1 was obtained through a two-step substitution reaction and deprotection. The pure target 1 was afforded by recrystallization from ethanol with an overall yield of 74.6％ (based on 3) and HPLC purity of 99.85％ , while individual impurity below 0.05％ . By replacing the deprotection reagent with trimethylsilyl trifluoromethanesulfonate(TMSOTf), the process was stabilized and simplified, significantly reducing the formation of the dimer impurity of 1(namely related substance B). This optimized process was suitable for industrial production. Furthermore, nine related substances were synthesized, among which the synthetic routes of related substances A, C, D, E, F, G, H, and I were reported at the first time. This study is expected to provide a valuable reference for the quality control of 1.

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.

对 FDA 微生物污染相关的药品召回事件执法报告中的制剂类型、召回原因、污染微生物种类等方面进行分析，了解 国外制药行业微生物控制的关注点，为我国药品的微生物质量控制提供参考。在微生物污染相关的召回案例中，无菌药品 召回 132 种次；非无菌药品召回 893 种次。无菌药品召回的原因主要为缺乏无菌保障 (54％ )；非无菌药品的召回原因主要 是非无菌药品微生物污染 (79.3％ )，其中洋葱伯克霍尔德菌群污染是典型代表。未明确鉴定结果的微生物污染在无菌药品 召回中占 81.8％，在非无菌药品中占 69.4％。美国的药品召回体系相对成熟，制药行业对于药品微生物质量控制不仅局限 于终产品，更贯穿至生产整个过程，值得我国借鉴。

An HPLC method was established to determine eleven synthetic phosphatidylcholine(PC) and phosphatidylethanolamine(PE) phospholipids. Consideration of the structural characteristics and retention behaviors in chromatography of the phospholipids, C8 chromatography columns with pore sizes of 12 and 15 nm(120 and 150 Å) were connected in series for the first time. The serial sequence was Welch Topsil C8 column(4.6 mm×250 mm, 5 μm, 15 nm) at front and Ultimate XB C8 column(4.6 mm×250 mm, 5 μm, 12 nm) at back. The analysis was carried out in the gradient elution mode with water-methanol-acetic acid-triethylamine as mobile phase A, and methanol-isopropanol-acetic acidtriethylamine as mobile phase B. The results showed that the minimum separation degree of eleven synthetic PC and PE was 1.0. It was linear for seven synthetic PC phospholipids in the concentration of 0.1 - 1.0 mg/mL, and it was linear for four synthetic PC phospholipids in the concentration of 0.03 - 0.30 mg/mL. RSDs of precision were all less than 2.5 ％ . And this separation method was successfully applied to the determination of synthesized phospholipids in two types of liposome injections and one excipient.

Geobacillus stearothermophilus(ATCC 12980)is commonly used to detect the sterilization effect of vaporized hydrogen peroxide. The study mainly discussed the effects of carriers and spore purity on the resistance of biological indicators(BIs) under vaporized hydrogen peroxide sterilization. The results showed that spore purity was negatively correlated with BIs resistance, poor carrier smoothness could also increase the resistance of BIs. Therefore, when accepting the BIs which used to monitor the vaporized hydrogen peroxide sterilization, besides the viable spore count, users should pay more attention to the carrier and the purity of the spores.

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.

Antibody drug conjugates(ADCs) are biotherapeutic agents composed of a monoclonal antibody covalently linked to a cytotoxic payload via a chemical linker. Their unique structure combines the dual advantages of antibody-mediated targeted delivery and the potent cytotoxicity, demonstrating remarkable clinical efficacy in solid tumors, hematological malignancies and other therapeutic areas. ADCs are expected to play a pivotal role in future global drug development. Throughout the entire lifecycle of ADC development, manufacturing, and quality control, their binding affinity and biological activity critically influence therapeutic efficacy and safety. Comprehensive characterization of in vitro biological activity not only serves as the cornerstone for ensuring the clinical performance but also drives the resolution of current technical challenges and the advancement of innovative drug development. This review systematically discusses the current in vitro biological activity evaluation methods of ADCs, focusing on five functional modules based on the mechanism of ADCs: target binding activity, internalization efficiency, payload cytotoxicity, bystander effect, and Fcmediated functions, aiming to provide methodological references for ADC development and quality control.

To investigate the effects of score design on the quality of scored tablets, five types of scored tablets were selected as models, and the effects of tablet shape, shape and depth of score line, tablet hardness on the partitioning capability of different specifications and different tablets were evaluated with tablet weight variation, mass loss, content uniformity, and dissolution/release as evaluation indicators. The results showed that capsule-shaped tablets were easier to be split than circular tablets. When the long-to-short axis ratio of the capsule-shaped tablet was less than 2, tablet weight variation could be improved by increasing the score line depth(approximately 0.5 mm). The recommended hardness range for sustained-release scored tablets was between 90 N and 130 N to maintain the integrity of the pellets; the recommended hardness range for orally disintegrating tablets was between 30 N and 50 N to meet the requirement of disintegration time limit within 60 seconds. Low dose(specification ≤ 10 mg) scored tablets should pay attention to the content uniformity of intact tablets(A+2.2S ≤ 7.0) and the mass loss( ≤ 0.8 ％ ) after segmentation to control the accuracy of tablet splitting. Manual and mechanical splitting showed no significant differences in various indicators of the segmented parts, fully complying with the requirements of Chinese Pharmacopoeia 2020 Edition and the related guidance. These findings validated the rationality of the model drug score design and provided guidance for scored tablets development.

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.

Traditional small molecule kinase inhibitor drugs face numerous challenges, such as the propensity for drug resistance and the problem that some targets are undruggable. The proteolysis targeting chimera(PROTAC) technology utilizes the inherent ubiquitin-proteasome system in cells to achieve the degradation of proteins of interest(POI) for treating diseases, which can avoid the limitations of undruggable targets and drug resistance. Therefore, the PROTAC technology is expected to overcome the limitations of small molecule inhibitors. At present, some PROTACs have entered the clinical trial stage and are expected to become potential treatment methods for many diseases. This review introduces the biological mechanism, technical advantages, molecular design and clinical application prospects of PROTAC, hoping to provide a reference for its drug development and clinical application.

蛋白质组学技术旨在全面分析蛋白质的表达水平、结构、功能、修饰状态以及蛋白质之间的相互作用，是目前常用 的高通量蛋白分析手段。蛋白降解靶向嵌合体 (PROTACs) 技术是利用生物体内天然存在的泛素 - 蛋白酶体系统降低靶标蛋 白表达水平的新型成药模式。文章总结了蛋白质组学技术在靶向蛋白质降解研究中 PROTACs 靶标蛋白的确认，分子配体 的设计、筛选和优化，靶标结合情况的鉴定，靶标敲除后的效率评价，以及通路验证的应用进展。

The active pharmaceutical ingredient in dry powder inhalers(DPIs) is usually an insulator with a small particle size that tends to exhibit significant electrostatic behavior in the preparation and usage stages of DPIs. It will cause a decrease in the flowability and an increase in adhesion of drug particles, which in turn will affect the content uniformity and the aerodynamic particle size distribution(APSD) after atomization, leading to a decrease in lung deposition and efficacy of drugs. This review introduces the generation of static electricity in DPIs, the influences of static electricity on the blending uniformity and APSD of DPIs and the commonly used methods for evaluating electrostatic potential to provide a reference for subsequent electrostatic research on DPIs.

随着我国化学仿制药一致性评价以及口服固体制剂和注射剂品种国家药品集中带量采购工作的推进，近年来不少企 业将眼用制剂列为战略重点，尤其是溶液型滴眼剂。近年来大量溶液型滴眼剂仿制药注册申报上市，文章参考《化学药品 仿制药溶液型滴眼剂药学研究技术指导原则》，结合溶液型滴眼剂仿制药的研究特点及多年来在溶液型滴眼剂方面的审评 经验，从规格与装量、处方、生产工艺、原辅料和包材、质量研究、稳定性等方面，对溶液型滴眼剂仿制药开发研究及生 产过程中药学方面的要求进行了阐述和探讨，以期为其研发和申报提供一定参考。

mRNA 技术已在疫苗领域成功应用。随着越来越多的 mRNA 疫苗上市，相关产品正逐步迈向产业化阶段，因此也面 临更多生产规范及质量合规性的挑战。文章分析了已上市 mRNA 疫苗的分子结构及其递送系统的设计关键，阐述了 mRNA 技术的应用现状及面临的法规要求，并结合监管视角，探讨了质粒模板生产、mRNA 体外转录、制剂中间体生产、制剂分 装等方面要求，旨在为 mRNA 疫苗产业的持续发展提供科学、实用的建议。

The synthesis of the antiplatelet aggregation inhibitor tirofiban hydrochloride(1) has been optimized. Ethyl n-butylsulfonyl-L-tyrosinate(5) was synthesized from ethyl L-tyrosinate(4) by sulfonylation. After the substitution of 5 with 4-(pyridin-4-yl)butyl-4-methyl benzenesulfonate(3), followed by the hydrolysis with lithium hydroxide, N-nbutylsulfonyl- O-[4-(4-pyridyl)butyl]-L-tyrosine(6) was obtained. Then, 6 was reduced by hydrogen in the presence of Pd/C and salted with hydrochloric acid to obtain the target compound 1. The overall yield was 63.5％ (based on 4) with purity of 99.80％ , and ee value of 99.8％ . The improved process has short steps with high product yield, economical and easily accessible raw materials, and mild and controllable reaction conditions, which is suitable for industrial production.