数据完整性一直备受全球制药界关注，因涉及产品质量，其监管要求不断提高。目前，中国、美国、英国和欧盟对 于数据完整性持续提出了监管新要求。文章分析了数据完整性的基本原则，归纳、总结了各国对于药品生产数据完整性的 要求，汇总了药品生产企业关于数据完整性缺陷方面的问题，进行举例和深刻剖析，并对生产设备、验证管理和记录管理 等涉及数据完整性的常见缺陷项整改措施提出建议，以期指导药品生产企业提高数据完整性管理。

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。

Momelotinib(1), a Janus kinase 1/2(JAK1/JAK2) inhibitor, was synthesized via a new synthetic route in three steps. The cyclization of ethyl 4-acetylbenzoate(2), N,N-dimethylformamide dimethyl acetal(DMF-DMA) and urea was achieved successfully to give ethyl 4-(2-oxo-1,2-dihydropyrimidin-4-yl)benzoate(3), which was subjected to the amination with 4-morpholinoaniline(4) in the presence of (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate(PyBOP) and 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU) to afford ethyl 4-[2-[(4-morpholinophenyl)- amino]pyrimidin-4-yl]benzoate(5). Compound 5 was subjected to the amidation with 2-aminoacetonitrile in the presence of air and potassium tert-butoxide to deliver the target product with purity of 99.5％ .This new synthetic route had fewer reaction steps and high overall yield(70％ based on 2).

Glioblastoma(GBM) is a highly malignant brain tumor with high disability and recurrence rate. Conventional treatment for GBM is prone to recurrence, and the prognosis of drug-resistant patients is unfavorable. Small interfering RNA(siRNA) can generate therapeutic effects by silencing specific genes and down-regulating protein expression, and can serve as a supplement to conventional treatment by inhibiting the development process of GBM. This review elaborates on the difficulties of siRNA delivery into the brain and the mechanism of GBM treatment by siRNA. Additionally, it summarizes the application of five non-viral siRNA delivery systems for GBM treatment, in order to provide a reference for the application research of siRNA in GBM treatment.

Due to its high bioavailability and good patient compliance, pulmonary inhalation administration has demonstrated significant clinical application value in the treatment of lung disorders and even plays a role in systemic therapy. However, there are numerous obstacles to drug delivery because of the unique physiological structures of the lungs. Nano drug delivery system has been widely used in pulmonary inhalation administration for its special benefits. This paper suminarizes the pulmonary drug delivery barriers and several inhalable nano drug delivery systems in detail, in order to provide reference for future clinical studies of pulmonary inhalation preparation.

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.

Nano spray drying is a mild and effective particle preparation technology. It innovatively adopts piezoelectric atomizing mechanism, laminar heating mode and electrostatic particle collection system, and has many advantages such as adjusting particle size, improving solubility, realizing surface modification. Nanoscale particles can be obtained with high output(90％ ) by this technology. The minimum sample volume processed by the nano spray dryer can reach milligram level. Starting from the development history and technical characteristics of nano spray drying technology, this paper introduces the structure and working mechanism of nano spray dryer, summarizes the formulation and process parameters affecting the properties of the obtained particles by nano spraying, and puts forward suggestions on their selection and optimization.

Periodontitis is a chronic infection of the periodontal tissue caused by the biofilm of dental plaque,
which can lead to tooth loosening, gum atrophy. Its main pathogenic bacteria include Porphyromonas gingivalis. Based on
the abundant blood vessels in the periodontal pocket, local delivery of antibacterial drugs can make drugs act directly on
the lesion site and improve the bioavailability. This paper focuses on introducing biodegradable local drug delivery systems
that have been marketed for the treatment of periodontitis, and summarizes the relevant drug prescriptions and preparation
processes, hoping to provide a reference for the development of new dosage forms for the treatment of periodontitis.

胶束制剂作为复杂制剂，能提高难溶性药物的载药量、改善药物体内药动学、提高药效、降低毒性，具有较高的临 床应用价值。然而，胶束制剂的技术壁垒高、研发难度大。目前，国内尚无胶束制剂的相关技术要求。该文参考胶束制剂 的国内外监管现状，结合实际审评工作经验，从聚合物辅料、临界胶束浓度、结构表征、释放度、体内释药行为和用法研 究方面，分析了胶束制剂质量研究的注意事项，为胶束制剂的开发和监管提供了参考。

Atezolizumab, as a new PD-L1 inhibitor drug, has become one of the hot spots in tumor immunotherapy research. This review takes atezolizumab as the research object, uses patent technology analysis to study the status of related patent applications, and focuses on the patent applications of atezolizumab in China from the perspective of its technical themes and patent layout, so as to provide some effective references and suggestions for domestic research institutions and enterprises in R&D and patent layout strategies of atezolizumab.

Microbial contamination is a major problem in the application of pharmaceutical purified water. Microorganisms can attach to solid surfaces and form biofilms by producing extracellular polymers, which can reduce the filtration efficiency of filtration units. They may also detach and enter the purified water distribution system, posing a risk to the quality and safety of pharmaceutical products. Therefore, it is necessary to explore methods for optimizing the current pharmaceutical purified water system process from the perspective of the three major factors influencing microbial growth in such systems: the surface area of the filtration media, the adsorbed nutrients, and the quantity of planktonic microorganisms. This exploration, combined with the concept of quality by design(QbD), aims to provide valuable insights and references for pharmaceutical manufacturers in addressing microbial control issues in pharmaceutical purified water systems.

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.

Due to various physiological and anatomical barriers in the human eye, the bioavailability of topical ophthalmic preparations, such as eye drops, is less than 5％ . While the bioavailability of drug-eluting contact lenses can achieve 50％ , and the products have the dual functions of drug release and visual correction. This paper reviews the research progress of preparation methods, sterilization and quality evaluation of drug-eluting contact lenses. The advantages and disadvantages of different preparation methods in drug loading and release, as well as the critical functional attributes of drug-eluting contact lenses are emphasized, hoping to provide some references for promoting the clinical application of medicated contact lenses.

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.

A highly sensitive LC-MS/MS method was established for detecting calcitriol content in human plasma, with a lower limit of quantification of 20 pg/mL, which could meet the clinical detection needs. A randomized, open, three cycles, triple crossover design was used to investigate and compare the pharmacokinetic characteristics and bioequivalence between the tested preparation and the commercially available reference preparation of calcitriol in 36 healthy Chinese volunteers who were given a single oral administration of calcitriol soft capsules(at a dose of 4.0 μg) on an empty stomach. The results showed that the main pharmacokinetic parameters of the tested preparation and the reference preparation were as follows: tmax were (3.46±1.33) and (2.92±1.47)h, t1/2 were (8.14±3.22) and (7.70±2.32)h, cmax were (160.68±52.41) and (169.00±50.26)pg/mL, respectively. The variance in plasma concentrations of the tested and the reference preparations showed the same trend. The geometric mean ratios of the main pharmacokinetic parameters were within the 90％ confidence interval of 80.00％ - 125.00％ , indicating that the test and reference formulations were bioequivalent.

In this study, human induced pluripotent stem cells(hiPSCs) were used to construct an in vitro organoid-based substitution model for drug cardiotoxicity. The hiPSCs were cultured to determine the optimal differentiation generation, and pluripotency was identified using immunofluorescence staining. The hiPSCs were seeded into ultra-low adsorption 96-well plates at different cell densities, and the medium containing growth factors and signaling pathway inhibitors were added for inducing differentiation, and the morphological changes and pulsatile characteristics were recorded by light microscopy. Cardiac organoids at different time points in the differentiation process were collected, and real-time reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was adopted to detect the relative expression of cell-specific genes of cardiac organoids. The results showed that the resuscitated hiPSCs grew well with clear edges and excellent cell pluripotency. The morphology of the differentiated cardiac organoids at a density of 5 000 cells per well was the best, and trended to be a relatively stable state for 8 - 10 d culturing, and a relatively stable state could be maintained within 18 d. RT-qPCR results showed that specific genes of cardiomyocytes and other cardiac components, such as endothelial cells, smooth muscle cells, and fibroblasts, were expressed. The establishment of cardiac organoid models in this study can more realistically and accurately simulate the biological characteristics and functions of the heart in vivo, which lays a foundation for the subsequent use of cardiac organoid models for potential cardiotoxicity studies of drugs in the early stage of research and development.

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.

In order to control the quality of cilastatin sodium(1), the synthesis of the related substances B, C and G involved in the EP 11.0, named (Z)-7-[[(2R)-2-carboxy-2-[[(1RS)-1-methyl-3-oxobutyl]amino]ethyl]- sulfanyl]-2-[[[(1S)-2,2-dimethylcyclopropyl]carbonyl]amino]hept-2-enoic acid, (Z)-7-[[(2R)-2-carboxy-2-[(1,1- dimethyl-3-oxobutyl)amino]ethyl]sulfanyl]-2-[[[(1S)-2,2-dimethylcyclopropyl]carbonyl]amino]hept-2-enoic acid and (E)-(2RS)-7-[[(2R)-2-amino-2-carboxyethyl]sulfanyl]-2-[[[(1S)-2,2-dimethylcyclopropyl]carbonyl]amino]hept-3- enoic acid, were reported in this study. Compound 1 was reacted with (E)-3-penten-2-one(2) or 4-methyl-pent-3-ene-2- one(3) via Michael addition, respectively, and purified by preparative chromatography to obtain related substances B and C. Ethyl (Z)-7-chloro-2-[[(benzyloxy)carbonyl]amino]hept-2-enoate(5) was synthesized through condensation of ethyl- 7-chloro-2-oxohept-2-enoate(4) and benzyl carbamate. The double bond of 5 was migrated by 2,2,6,6-tetramethylpiperidine lithium(LiTMP) to generate ethyl (E)-7-chloro-2-[[(benzyloxy)carbonyl]amino]hept-3-enoate(6). After deprotection of 6, followed by reaction with (S)-2,2-dimethylcyclopropane carboxylic acid(8) to obtain ethyl (E)-7-chloro-2-(S)-2,2- dimethylcyclopropane carboxamido)hept-3-enoate(9). Related substance G was obtained via the reaction of 9 and Lcysteine( 10) and the preparative chromatography. The structures of the three target products were confirmed by MS, 1H NMR and 13C NMR.

This study prepared three impurities of alprazolam(1) namely impurities D, H, and J, which were recorded in the EP10.0, but their synthetic routes had not been reported in the literature. Additionally, during the stability study of 1 bulk drug, a new impurity Q was discovered. Its chemical structure was determined as [5-chloro-2-[3-[[[(7- chloro-5-hydroxy-5-phenyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1-yl)methyl]amino]methyl]-5-methyl-4H-1,2,4- triazol-4-yl]phenyl](phenyl)methanone through high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. The successful preparation of these four impurities is of great significance for the quality research of 1 bulk drug and its 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.

生物制品具有分子结构复杂、生物学活性易变和理化特性多样等特点，同时其生产工艺复杂、生产周期长，生产中 使用的各种原、辅材料亦来源多样，且制品组分一般不能耐受终端灭菌处理，导致其无菌保证方面存在特殊性。文章阐述 了无菌药品生产中微生物、热原和微粒等的污染控制策略，并重点探讨和分析了生物制品生产的无菌保证特殊性，以促进 行业提高生物制品的无菌保障能力和水平，确保生物制品安全。

As an endogenous messenger molecule, nitric oxide has multiple effects in tumor treatment. It can not only induce tumor cell apoptosis but also achieve outstanding synergy with other treatment methods. To improve its therapeutic efficiency, researchers have designed and prepared various types of nitric oxide nanodelivery systems and applied to tumor therapy research. Among them, the controllable responsive nitric oxide nanodelivery systems have received extensive attention for their excellent on-demand release ability and brilliant therapeutic effect. This article mainly reviews the controllable responsive nitric oxide nanodelivery systems based on different nanomaterials and discusses their applications in tumor therapy from endogenous-based and exogenous-based stimuli-responsiveness respectively, in order to provide a reference for the further development of nitric oxide nanodelivery systems.

Self-microemulsifying drug delivery system(SMEDDS) is one of the effective approaches to improve the solubility and bioavailability of poorly soluble drugs. The formulation screening and optimization is the key steps in the development of SMEDDS products. Design of experiment(DoE) methods are employed to evaluate the main effects of independent variables and their interactions on response variables in formulations, therefore they are widely used in formulation optimization. This review summarizes the principles, advantages and disadvantages of several experimental design methods and their application in SMEDDS products development, focusing on the D-optimal mixtures design, in order to provide some references for the selection of SMEDDS formulation optimization methods.

The paddle apparatus is commonly used in both research and development(R&D) and quality control. However, because the settling position of the product after falling into the dissolution vessel may change the diffusion range of drug disintegration at the bottom of the vessel, it is often affected by the problems of reproducibility and accuracy, which may not reflect the drug release characteristics precisely. To achieve better reproducibility, the new modified paddle apparatus was improved by adding auxiliary beads at the bottom of the glass vessel of the paddle apparatus. In addition, the size of the auxiliary beads can be selected according to the dissolution behaviors of different drugs. In this study, entacapone(1) tablets, dapagliflozin(2) tablets and clarithromycin(3) tablets were used as model drugs to Investigate the effects of the improved paddle apparatus, traditional vessel and apex vessel. The results indicated that the improved paddle dissolution vessel could not only select the corresponding auxiliary beads more flexibly according to the drugs, but also obtain better reproducibility of the drug release curves, which was beneficial to the comparison of dissolution results between batches or laboratories.

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.

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。

Hollow fibers are a type of chemical fiber material with a linear tube like cavity. The membrane wall is densely packed with micropores, which can intercept macromolecular substances and serve as a carrier for cell growth. They are widely used in the field of pharmaceutical science, including screening of active ingredients in natural drugs, sample pretreatment, microextraction, construction of pharmacokinetic and pharmacodynamic models. This paper elaborates the current application status of hollow fibers, which provides a reference for further exploration of the application in the pharmaceutical field.

In order to effectively control the quality of pranoprofen(1), four related substances were
synthesized, namely 2-(5H-chromeno[2,3-b]pyridin-7-yl)acrylic acid(related substance A), 2-(5-oxo-5H-chromeno[2,3-b]-
pyridin-7-yl)propanoic acid(related substance B), 2-hydroxyl-2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoic acid(related
substance C), 2-(5-hydroxy-5H-chromeno[2,3-b]pyridin-7-yl)propanoic acid(related substance D), and their structures
were confirmed by 1H NMR, 13C NMR and MS. The synthetic routes of these four related substances were short with mild
reaction conditions, and their purities were more than 98.5％ , providing some references for the the quality control of 1.
Among them, the synthesis routes of related substances A and C were reported at the first time.

The sources of eight related substances in the crude product of cisatracurium besylate(1) were analyzed, and the related substances A, B, C, D, F, H, O included in EP and the non-pharmacopoeial impurity(6), named (1R,2R)-1-(3,4-dimethoxybenzyl)-2-(3-ethoxy-3-oxo-propyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolinium benzenesulfonate were synthesized by the acid hydrolysis and esterification with (1R,2R)-1-[(3,4-dimethoxyphenyl)methyl]- 2-[3-(tert-butoxy)-3-oxy-propyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinolinium benzenesulfonate(4) as the starting material. The structures of these compounds were confirmed by 1H NMR, 13C NMR and HRMS analyses. Additionally, a crystallization process with obvious impurity removal effect and high yield was developed, which was suitable for industrial production.

Several nanoemulsions with different contents of ω-3 polyunsaturated fatty acid glyceride were prepared by the high-speed shearing and high-pressure homogenization method and their effects on the treatment of liver injury were investigated. The combination of optimized process parameters selected through the experiment of single factor was as follows: the oil phase and the water phase were sheared at a shearing speed of 8 000 r/min for 5 min at 60 ℃ , and then homogenized at a pressure of 60 000 kPa for 6 cycles. The nanoemulsion prepared with the optimized process parameters presented a white emulsion appearance, with an average particle size of approximately 200 nm and a pH value of approximately 7.4, and all indicators met the quality requirements. The results of the cell uptake test showed that the prepared nanoemulsions could be effectively taken up by human fetal hepatocyte cell line(LO2 cell), and the uptake amount was positively correlated with the ω-3 polyunsaturated fatty acid content. As for the cholestatic liver injury model mouse, tail vein injection of nanoemulsions could effectively improve liver injury, and the nanoemulsions with a high ω-3 polyunsaturated fatty acid glyceride content showed a better therapeutic effect on liver-injured mice. In conclusion, the ω-3 polyunsaturated fatty acid glyceride nanoemulsions prepared in this study had a significant improvement effect on liver injury and good clinical application potential, providing an effective reference for the optimal design of injectable glyceride nanoemulsion drugs.

瑞士型权利要求是我国专利审查实践中唯一接受的医药用途专利撰写方式。该权利要求通过增加“制备”一词使其 性质成为制备方法权利要求，从而在侵权行为规制和新颖性审查标准方面存在难以避免的缺陷。因此，文章提出建议，将 现医药用途发明的撰写形式修改为其他非瑞士型权利要求形式。

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.

The acid water extraction method was designed, and a new refining process for the sinomenine extraction solution was developed. Experimental parameters for extraction and purification were determined by computational optimization, and experimental verification was performed. Chloroform was recycled for 10 times. The content of sinomenine hydrochloride in the prepared product was determined by HPLC. The experimental parameter ranges were set as follows: in the alkaline system(E1), the pH value ranged from 9 to 10. During the extraction process, the volume ratio of chloroform to E1 was 1 ∶ 10. During the water-washing process, the volume ratio of organic phase(O1) to water was 1 ∶ 3. During the acid-water stripping process, the volume ratio of organic phase(O2) to water was 1 ∶ 8. In the aqueous phase(A1), the pH value ranged from 4 to 5. Under the same feed amount, after chloroform was reused for five times, the purity of prepared sinomenine hydrochloride maintained stable. This study developed a new process for the preparation of sinomenine hydrochloride, demonstrating the feasibility of recycling chloroform and obtaining high-purity sinomenine hydrochloride, which could reduce solid waste and production costs.

As the population ages, the need for medications tailored to older adults becomes increasingly critical. Due to pathophysiological changes, comorbidities, and polypharmacy, older adults may respond differently to drugs than younger individuals. This necessitates targeted drug development and adjusted dosages. However, older adults, particularly those over 80 years of age, are often underrepresented in clinical trials. This lack of research data hinders the safe and effective use of medications in this age group. New drug development and clinical research hold immense potential for improving the well-being of older adults. To achieve this, strong collaboration between governments, pharmaceutical companies, and research institutions is essential. In-depth studies on how medications interact with the aging body are crucial. Furthermore, establishing a robust scientific evaluation system, informed by both policy and scientific advancements, is paramount to ensure the safety and efficacy of medications for older adults. This article explores key considerations for new drug development and clinical research specific to this growing demographic, taking into account both domestic and international regulatory developments.

The main metabolites of linezolid, PNU-142300(2) and PNU-142586(3), were synthesized. Compound 3,4-difluoronitrobenzene(5) was used as the starting material to synthesize the key intermediate (S)-2-[[3-[4-[benzyl[2- [(tert-butyldimethylsilyl)oxy]ethyl]amino]-3-fluorophenyl]-2-oxooxazolidin-5-yl]methyl]isoindoline-1,3-dione(15) by nucleophilic substitution, hydroxyl protection, nitro-reduction reaction, condensation and cyclization. Metabolite (S)-2-[2-[[4-[5-(acetamidomethyl)-2-oxooxazolidin-3-yl]-2-fluorophenyl]amino]ethoxy]acetic acid(namely PNU- 142300) was obtained from 15 by removal of tert-butyldimethylsilyl(TBS) group, Williamson etherification, amolysis, acylation, debenzylation and removal of tert-butyl group in sequence with total yield of 78％ and the purity of 98.62％ . Metabolite (S)-N-[4-[5-(acetamidomethyl)-2-oxooxazolidin-3-yl]-2-fluorophenyl]-N-(2-hydroxyethyl)glycinate (namely PNU-142586) tetrabutylammonium salt was obtained from 15 by amolysis, acylation, debenzylation, nitroalkylation, debenzylation and TBS removal in sequence with total yield of 65％ and the purity of 92.35％ . The structures of 2 and 3 were confirmed by MS, 1H NMR and 13C NMR.

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。

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.

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.

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.