In 2025, FDA approved 46 new drugs for marketing, including 31 small molecule drugs and 15 biological products. Based on FDA-approved drug labeling, related databases, patents, and published literature, this review describes the chemical name, original research company, compound patent, time to market, indications, mechanism of action, dosage form and strengths, adverse effects and synthesis routes of those small molecule drugs, and the basic information about biological products.

Antibody-drug conjugates(ADCs) are novel antineoplastics that combine the high targeting speciffcity of monoclonal antibodies with the potent cytotoxicity of small-molecule toxins. By selectively delivering cytotoxic payloads to tumor cells, ADCs achieve effective tumor cell killing while minimizing damage to healthy cells and reducing systemic toxicity. These innovative agents, often referred to as “biological missile”, are leading a new era in targeted cancer therapy. Although three generations of ADCs have been applied to cancer treatment, further optimization of the components of ADCs is still required to address challenges such as stability, cytotoxicity, and drug resistance. This article summarizes the approved ADCs and those under clinical research, outlines innovative directions for next-generation ADCs, to provide insights for advancing research and development of novel cancer treatments using ADC technology.

Probiotic exosomes are nanoscale vesicles secreted by probiotics, which are capable of carrying various bioactive molecules such as proteins, nucleic acids and lipids. In addition to regulating host immunity, maintaining intestinal microecological balance, and exerting antimicrobial effects, they possess multiple biological functions including intestinal barrier protection, metabolic regulation, and neuroregulation. This review summarizes recent research progress of probiotic exosomes, systematically outlines the specific functions and potential action mechanisms of exosomes derived from different probiotic sources, and deeply explores their application prospects and industrial advantages in disease therapy, drug delivery and vaccine development. On this basis, this review points out current technical and translational bottlenecks in this field, aiming to provide new insights and directions for the subsequent basic research and industrial applications related to probiotic exosomes.

Central nervous system(CNS) diseases have become a major global public health challenge. Intranasal administration offers a promising, non-invasive delivery route for drugs to the brain by bypassing the blood-brain barrier, avoiding the ffrst-pass effect, achieving high bioavailability of drugs in the brain, as well as improving patient compliance and convenience. However, conventional intranasal delivery is limited by rapid mucociliary clearance and poor targeting efffciency. Nano drug delivery systems exhibit unique advantages, such as a high speciffc surface area, adjustable structure and modiffable surfaces, which could improve drug stability, prolong mucosal retention and enhance targeted delivery to the brain. The integration of nose-to-brain targeting strategies with nanotechnology offers a promising approach for efffcient drug delivery to the CNS. This review provides a systematic overview of recent advances in nose-to-brain nano drug delivery systems, focusing on key approaches to enhance delivery efffciency. It aims to offer theoretical guidance for the rational design and clinical translation of such systems.

An optimized synthetic route for mirogabalin besylate(1), a drug for the treatment of diabetic neuropathic pain in adults, was developed using 3-ethylbicyclo[3.2.0]hept-3-ene-6-one(2) as the starting material. The process involved chemical resolution, Wittig-Horner reaction, Michael addition, nitro reduction, secondary resolution, deprotection, and salt formation. In this optimal route, key improvements included enhancing the chiral resolution method and optimizing the nitro reduction step, which mitigated safety risks from Raney nickel hydrogenation. The overall yield increased from 8％ to 10.2％ (based on 2), with HPLC purity of the targeted compound reaching 99.2%. Featuring simple operation and reliable product quality, this route is suitable for industrial production.

Erdafitinib(1), a novel small-molecule targeted agent, is the first fibroblast growth factor receptor(FGFR) tyrosine kinase inhibitor approved for the treatment of advanced or metastatic bladder cancer. By selectively targeting genetic alterations in FGFR signaling pathways(such as mutations, fusions, or amplifications), it modulates cellular growth and division, thereby treating urothelial carcinoma of bladder and demonstrating broad clinical and commercial application prospects. This review systematically analyzes the synthetic strategies of 1, comprehensively reviews 9 reported synthetic routes of 1, and critically evaluates the advantages and limitations of each route. These abovementioned insights aim to offer valuable references and guidance for the synthesis research and industrial-scale manufacture of 1 and its key intermediates.

鼻用喷雾剂因吸收快、起效快、可避免首过效应、生物利用度高等优势，在治疗局部和全身疾病方面展现出巨大潜 力。但因作用部位的特殊性，且兼具药械组合产品属性，鼻用喷雾剂的临床研究及评价存在一些独特的挑战。例如，给药 过程的控制、局部药代动力学、鼻黏膜的刺激性和安全性、特殊人群的关注等问题。文章基于国内外发布的相关指南与建议， 结合对具体品种的临床审评报告和研究进展的解析，探讨了鼻用喷雾剂的临床评价要点考量，为鼻用喷雾剂的临床试验设 计与实施，以及相关产品的审评和核查提供了参考。

In order to formulate the pharmacopoeia standard of ambroxol hydrochloride inhalation solution, the key indicators of this product, including related substances, delivery characteristics, pH value, and osmolarity, were studied by referring to standards of four domestic enterprises. The methods for quality standard were optimized and veriffed according to the test results. The general methods and limits for accurately determining relevant substances, delivery characteristics, pH value, and osmolarity were ultimately established. This method was used to test and verify products from various manufacturers, and all results showed compliance. The newly established standards shall not be lower than the requirements of Pharmacopoeia of the People’s Republic of China for inhalation solutions and ambroxol hydrochloride injection, and can be used for quality control of ambroxol hydrochloride inhalation solutions from various manufacturers.

Epigenetics refers to the study of heritable changes in gene expression that occur without alterations to the DNA base sequence, primarily through mechanisms such as DNA methylation, histone modification, and non-coding RNA. Traditional genotoxicity testing focuses mainly on damage to the DNA sequence itself, making it difffcult to identify potential toxicity risks that do not involve sequence changes but may lead to long-term or transgenerational phenotypic effects. As research into epigenetic regulatory mechanism advances, the importance of epigenetics as a novel target for toxicity assessment has become increasingly evident. This article systematically reviews recently developed methods for detecting epigenetic alterations, including techniques for analyzing DNA methylation, histone post-translational modiffcation, and non-coding RNA. It compares the principles, advantages, and limitations of these methods and discusses their applicability across different application scenarios, providing a reference for selecting appropriate detection strategies in drug safety evaluation and related toxicological studies.

Co-amorphous drug delivery systems are homogeneous single-phase systems composed of two compatible drugs or a drug combined with a small-molecule ligand exhibiting high biosafety. As a highly promising formulation technology, these systems have been widely used to improve the critical in vitro and in vivo properties of poorly soluble drugs, including solubility, dissolution, physical stability, and bioavailability. This paper systematically reviews the latest research advances in this field, focusing on the classification, preparation techniques, physicochemical properties, and in vivo biological performance of drug co-amorphous systems, aiming to provide a reference for the development and application of co-amorphous drug delivery systems.

Small interfering RNA(siRNA) is a programmable gene-silencing therapeutic agent that can specifically downregulate the expression of pathogenic genes through the RNA interference mechanism, thereby exhibiting significant potential in precision therapy for respiratory diseases. In recent years, siRNA agents targeting key pathogenic genes in respiratory diseases have shown promising therapeutic efficacy in disease models such as lung cancer, asthma, COPD, and idiopathic pulmonary fibrosis. However, naked siRNA suffers from several limitations, including poor in vivo stability, high susceptibility to nuclease degradation, low transmembrane delivery efficiency, difficulty in penetrating the pulmonary mucus barrier, and inadequate endosomal escape capability, which severely hinder its clinical translation. To address these challenges, various nanoscale delivery systems, including lipid nanoparticles, polymeric nanoparticles, viral vectors, inorganic nanomaterials, and exosomes, have been developed for the efficient delivery of siRNA to pulmonary lesions. Centered on the “disease - siRNA target - delivery system” framework, this review systematically summarizes the research progress of representative siRNA-based nanoscale delivery systems for respiratory diseases. It critically examines how different nanocarriers influence siRNA delivery efficiency with respect to systemic circulation stability, pulmonary targeting, mucus penetration, cellular uptake, and endosomal escape. Furthermore, it outlines optimization strategies such as passive targeting, ligand modification, stimuli-responsiveness, and biomimetic modification, aiming to provide a reference for further research and clinical translation of siRNA therapeutics for lung-targeted treatment of respiratory diseases.

The synthetic process of asciminib hydrochloride, a drug for treating chronic myeloid leukemia, was optimized. Methyl 5-bromo-6-chloronicotinate(2) was used as the starting material and condensed with (R)-pyrrolidin3-ol(3) to generate methyl (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl) nicotinate(4). Compound 4 was subjected to Suzuki coupling reaction with 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester to produce methyl 6-[(R)-3-hydroxypyrrolidin-1-yl]-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl] nicotinate(6). Compound 6 was coupled with 4-(chlorodifluoromethoxy) aniline to produce (R)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-N- [4-(chlorodiffuoromethoxy)phenyl]-6-(3-hydroxypyrrolidin-1-yl) nicotinamide(8). Then compound 8 was deprotected to obtain free base of asciminib(1), while 1 was ffnally saliffed to obtain asciminib hydrochloride. Overall yield was 39.27％ (based on 2) with purity of 99.89％ and ee value of 99.88％ . The optimized synthesis process of asciminib hydrochloride has mild conditions, controllable quality, and simple operation, which is suitable for industrial production.

Host cell proteins(HCPs) are critical impurities that are difficult to remove completely during biopharmaceutical production. Their residual presence may compromise product safety, efficacy, and stability, while potentially inducing immune responses. Characterized by low abundance, HCPs demand exceptionally high detection sensitivity. Therefore, the precise quantification and rigorous control of HCPs are of paramount importance in biopharmaceutical quality assurance. This paper systematically reviews the current global regulatory status of HCPs, and analyzes the principles, application status, advantages and disadvantages of existing quality control technologies(including traditional detection methods and emerging technologies), providing a more comprehensive framework for HCPs control. Furthermore, it systematically addresses the major challenges encountered in HCPs detection, aiming to establish a theoretical foundation for future research and development of related technologies, as well as for drug regulation.

As an alternative to traditional dissolution test methods, the ffow-through cell method offers many advantages over the traditional apparatus. In recent years, with the deeper studies of drug release mechanism and the updating and development of preparation technologies, the application range of the ffow-through cell method has been expanding. This paper reviews the application and research progress of the ffow-through cell method in drug dissolution/release studies, with a focus on its advantages in dosage forms such as tablets, capsules, suppositories, and semi-solid preparations, as well as its in vitro-in vivo correlation, to provide a reference for the further optimization of this method.

Sevoflurane(1) is a widely used inhalation anesthetic. To address the issues in existing synthetic techniques, this study developed the continuous gas phase synthesis of 1. Using Cr-Ce@C as the catalyst and hexafluoroisopropyl chloromethyl ether and hydrogen fluoride as raw materials, the gasified and mixed reactants flowed into the catalytic bed for a fluorine-chlorine exchange reaction. After 33 min of operation, the conversion rate of chloromethyl ether and the selectivity for 1 reached 92％ and 97％ , respectively. The isolated yield of target product 1 was 80％ with a purity of 99％ . This method demonstrated excellent selectivity, safe control, and showed significant potential for continuous large-scale production and automated process control.

Enzymatic catalysis, which uses enzymes as the core catalyst, has been widely applied in the synthesis of chiral drugs due to its advantages of mild reaction conditions, high stereoselectivity, and low environmental pollution. Common types of biocatalytic reactions include ketoreductase, imine reductase(IRED), transaminase(TA), hydrolase, and amino acid dehydrogenase. This paper focuses on the mechanisms of IRED and TA, as well as their applications in the synthesis of 15 marketed chiral amine drugs(with 6 cases having achieved large-scale production). It also provides an outlook on the diversiffed applications and future development directions of biological enzyme catalysis to address the opportunities and challenges of this technology in the future.

RNA-based therapeutics represent a pivotal modality in precision medicine, and their clinical advancement hinges on the development of highly efffcient and safe delivery systems. Given their superior safety, substantial drug-loading capacity, and scalability for industrial production, non-viral delivery systems have become predominant in the ffeld. This review systematically summarizes the approved RNA drugs and analyzes their core delivery strategies in detail. Furthermore, it discusses the key bottlenecks limiting the clinical translation of non-viral platforms, including low delivery efficiency, inefficient endosomal escape, short systemic circulation time, and insufficient extrahepatic targeting capabilities, as well as existing mitigating strategies, with the aim of promoting more effective clinical transformation of RNA therapeutics.

A randomized, two-period cross-over design was conducted to evaluate the pharmacokinetics and bioequivalence of two brands of tofacitinib citrate extended-release tablets in healthy volunteers. Following a single oral dose of the test(T) and reference(R) preparations, plasma concentrations of tofacitinib at different time points were measured using a validated LC-MS/MS method. The main pharmacokinetic parameters of T and R preparations were calculated and listed as follows: under fasting conditions, cmax were (53.84±11.48) and (55.54±13.22)ng/mL, AUC0→t were (379.75±79.20) and (376.76±90.97)ng·h·mL–1 ，AUC0→∞ were (383.30±79.06) and (387.94±82.67)ng·h·mL–1 . Under fed conditions, cmax were (72.09±16.39) and (69.49±16.52)ng/mL，AUC0→t were (385.10±85.75) and (386.83± 89.69)ng·h·mL–1 ，AUC0→∞ were (391.76±87.17) and (391.29±96.47)ng·h·mL–1 . The results showed that under fasting and fed conditions, there were no signiffcant differences in above parameters between T and R preparations(P>0.05). The geometric mean ratios of the main pharmacokinetic parameters for T and R preparations both fell within the 90％ confdence interval of 80.00％ - 125.00％ . No serious adverse events were observed during the study, all reported adverse events were Grade 1 in severity. These results indicated that the T and R preparations were bioequivalent in Chinese healthy volunteers with acceptable safety and tolerability, supporting the potential for domestic substitution of tofacitinib citrate extended-release tablets.

抗体偶联药物 (ADCs) 通过将高活性有效载荷精准递送至靶细胞，实现了对细胞的特异性杀伤。通常，有效载荷先 通过连接子化学结合形成有效载荷 - 连接子复合物，再与抗体偶联，组装为完整 ADCs。目前全球已上市的 ADCs 均用于肿 瘤治疗。在我国，ADCs 作为生物制品进行注册管理，其中的有效载荷 - 连接子部分通常被视为传统小分子化合物。因此， ADCs 的研发与评价涉及多学科协同合作。目前，我国已发布了与 ADCs 相关的药学技术指导原则，明确了其中小分子部 分的药学研究一般要求。该文章结合实际，从小分子部分的设计、生产工艺与控制、杂质分析、质量控制及稳定性研究等 方面，深入探讨了其药学研究要点。

混悬型滴眼液可延长药物作用时间，提高药物生物利用度，临床价值显而易见。然而，国内目前尚无按新注册分类 获批的混悬型滴眼液仿制药，且国内外药品监管机构暂未发布混悬型滴眼液的相关技术指导原则。相较于药液直接湿热灭菌， 混悬型滴眼液在无菌工艺背景下的分步灭菌操作对车间洁净度、生产设备、接触物料的容器等要求更高，且受多方面因素 影响。为促进我国混悬型滴眼液进一步发展，文章基于文献调研及审评经验，结合案例分析，重点对制约混悬型滴眼液研 发的灭菌 / 无菌工艺进行探讨，分析混悬型滴眼液制备过程中可能涉及的湿热灭菌、辐照灭菌、环氧乙烷气体灭菌等工艺 操作中的关注点，以期为混悬型滴眼液及相关眼用新剂型仿制药的高质量发展提供一定参考。

Various nature products have been veriffed to enhance the antitumor efffcacy of paclitaxel and mitigate its toxic and adverse reactions. However, the co-delivery of paclitaxel and natural products remains a signiffcant challenge in the pharmaceutical ffeld. In recent years, strategies such as drug self-assembly, drug carriers, and new formulation forms have been employed to concurrently deliver natural products and paclitaxel to tumor sites, aiming to exert their synergistic effects, thereby elevating antitumor activity of paclitaxel and circumventing drug resistance. This article systematically reviews relevant literature, focusing on the design strategies, release characteristics, and therapeutic effects of co-delivery systems, with the aim of providing insights and references for antitumor research combining paclitaxel and natural products.

An improved synthetic process of tofacitinib citrate(1) was reported. 4-Chloro-7H-pyrrolo[2,3-d]- pyrimidine(2) was protected with p-toluenesulfonyl, followed by substitution with (3R,4R)-N,4-dimethyl-1-benzyl3-piperidinamine dihydrochloride, then deprotection, hydrogenation and salification to give N-methyl-N-[(3R,4R)-4- methylpiperidin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride(7). Subsequently, the condensation of 7 with cyanoacetic acid N-hydroxysuccinimide(9, obtained by esteriffcation of cyanacetic acid), followed by the saltiffcation with citraric acid to obtain tofacitinib citrate 1, with an overall yield of 47.7％ (based on 2). The ffnal product 1 showed a purity of over 99.9％ , without signiffcation impurities. The improved process shortened heterogeneous reaction times, moderated deprotection conditions, and improved quality of the key intermediates 7 and 9. These modiffcations resulted in an elevated overall yield and delivered high-purity product, which is suitable for industrial-scale production.

Using 2-chlorotrityl chloride resin as the carrier, five natural amino acids(L-valine, L-tyrosine, L-glutamine, L-alanine, and L-alanine), one special amino acid(D-allo-threonine), and one chiral fatty side chain(5- hydroxytetradecanoic acid) as raw materials, the linear peptide was synthesized by Fmoc solid-phase synthesis with O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate/1-hydroxybenzotriazole as the condensation system. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/4-dimethylaminopyridine was used as the cyclization system, followed by deprotection with triffuoroacetic acid and rapid column chromatographic puriffcation to obtain the anti-tuberculosis drug, cordycommunin(1). The structure of 1 was conffrmed by 1 H NMR, 13 C NMR and high resolution mass spectrometry(HRMS). After separation and puriffcation, (R)-1[yield of 28.5 ％ (calculated based on L-valine) with the purity of 98.2％] and (S)-1[yield of 23.7％(calculated based on L-valine) with the purity of 97.5％] were obtained. This method is simple and suitable for the synthesis of this series of cyclic peptides, providing a certain reference for the further research and application of highly anti-tuberculosis active cyclic peptides.

Taking Xiao’er Qixingcha prescription, Xiaochaihu prescription and Fenghan Ganmao prescription as models, composite particles were prepared from the aqueous extracts of each prescription via co-spray drying technique with hydroxypropyl-β-cyclodextrin(HP-β-CD) as a modifier. The properties of the spray-dried feed solution, the structure properties, surface free energy and flowability of the obtained composite particles, as well as the compactibility and disintegration time of the tablets were comprehensively characterized. The results showed that compared with the corresponding original extract powders, the yields of the composite particles with HP-β-CD were increased by 4.4％ - 11.7％, and their morphology were smoother and more regular. The particle size of the composite particles increased by 17.0％ - 25.0％ , and the cohesion index, caking strength, dispersive component, and surface free energy decreased by 8.3％ - 35.6％ , 12.7％ - 74.1％ , 9.9％ - 15.5％ , and 2.4％ - 4.0％ , respectively. The ffowability and compactibility of the composite particles were significantly improved, with the angle of repose, Carr index, Hausner ratio decreased by 3.5％ - 5.3％ , 4.6％ - 9.3％ , and 2.5％ - 5.1％ , respectively. Meanwhile, the tensile strength of the tablets compressed from the composite particles increased by 13.6％ - 45.7％, and the disintegration time decreased by 14.6％ - 16.2％. This study demonstrates that co-spray drying with HP-β-CD can signiffcantly improve the structure properties, reduce the surface free energy and enhance ffowability of the traditional Chinese medicine powders, and shorten the disintegration time of the tablets. This research can provide some references for the development of the co-processing modiffcation technology of traditional Chinese medicine powders and direct powder compaction technology.

A series of matrine(1) derivatives were designed and synthesized. Based on the tetracyclic rigid scaffold of 1 as the parent core, structural modifications were carried out by introducing a thione group at the C15 position and installing substituted cinnamamidomethyl or heteroaromatic amidomethyl groups at the C13 position. This strategy yielded twelve novel derivatives(B1 - B9 and E1 - E3), whose structures were fully characterized by ⊃1;H NMR, ⊃1;⊃3;C NMR, and HRMS. The anti-inflammatory activities of these compounds were evaluated in lipopolysaccharide-induced RAW264.7 macrophage cells. At a concentration of 12.5 μmol/L, all derivatives inhibited nitric oxide(NO) production more effectively than the parent compound 1[(41.15±0.23)％ ]. Notably, compounds B1 - B3 exhibited superior inhibitory activities[(70.40±0.83) ％ , (71.10±0.69) ％ and (71.89±0.71) ％ , respectively]), outperforming the reported positive control 13-methylamino-18-thiomatrine[(64.68±0.39)％ ]. Structure-activity relationship analysis suggested that introducing a substituted cinnamamidomethyl moiety at C13 enhanced anti-inflammatory potency. Among them, compound B3 demonstrated strong inhibitory effects on key inflammatory mediators, including NO, IL-6, and TNF-α, indicating its potential as a promising anti-inflammatory lead compound for further development.

Solvent-free styrene-isoprene-styrene(SIS) block copolymer-based hot melt pressure sensitive adhesive(HMPSA) is commonly used as transdermal patch matrix due to its advantages of environmental protection, high adhesion strength and good drug compatibility. However, the aging problem in its long-term storage and use will lead to problems such as viscosity attenuation and abnormal drug release, which restricts its clinical application and industrialization promotion. This paper mainly introduces the material properties, aging types and mechanisms of solventfree SIS-based HMPSA, systematically summarizes the aging characterization techniques and evaluation methods, and the current commonly used anti-aging strategies. Based on the existing research progress, this paper analyzes the advantages and limitations of different strategies, and puts forward the future research direction, aiming to provide a reference for the development of anti-aging properties of HMPSA for transdermal patches.

Dexmethylphenidate hydrochloride resin complexes(dMPH-DRC) and their sustained-release microcapsules(dMPH-CM) were prepared using ion exchange resin and immersion coating technology. The preparation processes of dMPH-DRC and dMPH-CM were optimized by single factor tests. The results showed that Amberlite ® IRP69 (drug-to-resin mass ratio of 1 ∶ 1.5) exhibited the good drug loading performance. The prepared dMPH-DRC could achieve a drug loading capacity of (37.1±0.4) ％ and a drug utilization rate of (87.1±0.2) ％ . X-ray powder diffraction, polarizing light microscopy and differential scanning calorimetry analyses revealed that the drug-resin interaction was not merely physical adsorption. The sustained-release effect of dMPH-CM was primarily inffuenced by the coating material type and concentration, drug loading of the drug resin complex and preparation temperature. The optimized sustained-release microcapsules had a drug content of (36.75±0.34) ％ , an average particle size of (105±5)μm, a continuous and dense coating membrane, and a sustained-release duration of 12 hours. This simple preparation method provides a new approach for developing dexmethylphenidate sustained-release formulations.

The applicability of culture media after 4-hour exposure for dynamic monitoring of settling microbes in cleanrooms was validated in this study. Referring to the technical requirements of Appendix Ⅰ of “Good Manufacturing Practice (2010 Revision)”(GMP) and Chinese Pharmacopoeia 2020 Edition(ChP 2020) Part Ⅳ , General Chapter 9205, six groups of 40 prefilled plates(with 90 mm diameter) containing tryptic soy agar(TSA) were separately exposed in a biosafety cabinet for 30 min and 4 h, respectively. After exposure, the plates were weighed to calculate water loss rate, and media applicability was validated using the spread plate method in accordance with the ChP 2020 General Chapter 1105. The results showed that under the conditions of temperature of 17 - 26 ℃ , relative humidity of 12％ - 63％ , descending airflow velocity of 0.32 - 0.33 m/s, and inflow airflow velocity of 0.54 - 0.56 m/s, the maximum water loss rate of the medium was 27.84％ , and the recovery ratios of all tested bacteria ranged from 0.5 to 2.0. This study confirmed that the 4-hour exposure of culture medium for dynamic monitoring of settled plates in cleanrooms met the requirements of General Chapter 1105 of the ChP 2020 .

Liposomes are widely used in drug delivery due to their excellent biocompatibility and surface modiffability. Functionalized liposomes represent a key research direction in liposome technology. This review summarizes surface modiffcation strategies for functionalized liposomes, including stimuli-responsive(pH value, redox, enzyme, and thermal/magnetic/optical/acoustic triggers), active targeting(antibody/aptamer/peptide), and biomimetic coatings, along with their applications in drug delivery. It also analyzes the limitations of functionalized liposomes, aiming to provide a reference for further research and application in this ffeld.

文章系统回顾2016 至2024 年我国批准上市的1 类创新药品种现状与市场情况。从药品数量、药品类型、药品生产 区域布局、治疗领域分布、纳入加快上市通道和出海等多个维度，深入剖析我国创新药上市现状和发展趋势。我国药品创 新水平逐步提升，1 类创新药从化学药为主转变为化学药和生物制品双轮驱动的创新研发格局，同时1 类创新药在国内首 次获批时间与在境外首次获批时间的差距正逐步缩短，标志着我国医药产业从“仿制药开发”向“创新药突破”的转型已 初见成效。文章旨在为我国创新药的未来研发布局提供一定的参考。

鼻用喷雾剂具有给药方便、分布均匀、不易流失及生物利用率高等优点，是目前研发和使用非常广泛的鼻用剂型。 鼻用喷雾剂尤其适用于鼻部疾病的治疗 ；同时在全身甚至脑部疾病的治疗中展现出巨大潜力。因鼻用喷雾剂具有药械组合 产品性质，且不同动物种属鼻腔结构差异大、存在局部暴露和系统暴露双重性、递送剂量的稳定性与均一性监控难度大等 特点，其非临床研究的设计、操作和评价较为复杂，需特别关注实验动物的选择、给药方式和周期、鼻黏膜毒性、肺部影响、 全身和中枢神经系统不良反应等。本文参考国内外监管指南、文献报道和具体审评案例，探讨了鼻用喷雾剂非临床评价重 点和难点。

随着科技发展，间充质干细胞 (MSC) 技术成为生物医药热点，全球已有十余款 MSC 药品上市。2025 年 1 月，我国首款 MSC 药品获批上市，标志着我国进入了 MSC 商业化时代。但 MSC 药品生产流程复杂，产品质量受多种因素影响，且无菌生产面临的挑战大，构建其科学质量管理体系至关重要。文章围绕 MSC 药品生产系统，从原材料控制、细胞库管理、生产过程控制、质量检测等环节展开讨论，系统剖析了 MSC 药品生产质量管理要点，为提升 MSC 药品质量与安全性、降低产品风险、推动行业规范化发展提供参考。

An improved synthetic process of ruxolitinib phosphate(1) was developed. Starting from (4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate(2) and 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-pyrazole(3), [4-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin- 7-yl]methyl pivalate(5) was prepared via Suzuki-Miyaura coupling reaction. Compound 5 was deprotected by hydrochloric acid to afford [4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate(6). Subsequent Michael addition of 6 with 3-cyclopentylacrylonitrile(4) furnished the racemic [4-[1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl]- 7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate(7). Chiral resolution of 7 using D-(+)-dibenzoyl-L-tartaric acid[D-(+)- DBTA] afforded (2S,3S)-2,3-Bis(benzoyloxy)succinate salt of (R)-[4-[1-(2-cyano-1-cyclopentylethyl)- 1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate(8). Deprotection and hydrolysis of 8 with sodium hydroxide yielded ruxolitinib(9). Finally, the target product 1 was available from 9 by saliffcation reaction with phosphoric acid and recrystallization. The overall yield was 27％ (based on 2), with the purity of 99.89％ and the chiral purity of 99.88％ , and the maximum single impurity less than 0.1％ . The improved process features simple operation and has been veriffed by pilot-scale production, which was suitable for industrial production.

目前细胞治疗产品生产企业对无菌工艺模拟试验的认知和执行存在“不到位”的现象，部分药品生产企业在无菌工艺模拟试验中存在较大的试验设计问题。文章分析了细胞治疗产品无菌工艺模拟试验应考虑的要点，结合生产工艺、设施设备、物料、工作人员、生产环境和生产排产等因素进行最差条件评估，总结了细胞治疗产品无菌工艺模拟试验设计的实施要求，以期促进细胞治疗药品生产企业科学、合理地开展无菌工艺模拟试验，提高药品质量，从而保障患者安全。

To identify the structure and trace the source of an unknown impurity with a content slightly greater than 0.05％ in low-density polyethylene packaged drugs. Using levosalbuterol hydrochloride nebuliser solution as the model drug, the unknown target impurity was separated and puriffed via preparative HPLC, and its structure was conffrmed by high-resolution mass spectrometry, nuclear magnetic resonance, infrared spectroscopy. The results showed that the unknown impurity was phenylmethanol, which was originated from glue components in the product label rather than a degradation product of the drug itself. It could be classiffed as a general impurity with no new high-toxicity structure. This study provides a reference for the identiffcation of unknown impurities in low-density polyethylene packaged drugs and quality control of similar products.

随着 ChP 2025 年版将非蒸馏法纳入注射用水 (WFI) 制备的合规路径，制药行业迎来了技术革新的重要机遇。该文 以反渗透 - 电去离子 (RO-EDI) 系统为核心，对比传统蒸馏法与非蒸馏法在工艺原理、运行成本、水质控制等方面的差异， 构建基于膜分离技术的全流程质量控制体系。相较于传统蒸馏法，RO-EDI 系统在运行成本方面具有显著优势。通过引入长 短期记忆网络 (LSTM) 膜污染预测模型和可编程控制器智能控制系统，可实现水质参数的实时调控与发生异常时的快速响 应。此外，该研究探讨了微生物污染风险与膜污染控制的技术瓶颈，提出了涵盖预处理优化、在线监测及新型消毒技术的 综合解决方案。非蒸馏法在满足中国、美国及欧洲药典关键质量标准 ( 如电导率、电阻率、微生物限度 ) 的同时，展现了 绿色低碳和智能化的优势，为制药企业高质量发展提供了理论支撑与实践指导。未来，高性能膜材料开发与全球法规协同 将是推动非蒸馏法广泛应用的关键。

Heparin is widely used clinically as an anticoagulant drug, with its main source being porcine intestinal mucosa. Due to the impacts of the heparin sodium incident and the African swine fever incident, a supply shortage of porcinederived heparin was once caused. Therefore, the FDA encourages manufacturers to increase the supply of heparin from other sources to mitigate the risk associated with relying on a single source. This paper focuses on bovine-derived heparin, analyzing differences from porcine-derived heparin in relative molecular weight, anticoagulant activity, and chemical structure(including monosaccharides, disaccharides, and tetrasaccharides). And the research progress on the preparation of low molecular weight heparin(LMWH) from bovine-derived heparin is also reviewed. Unfractionated bovine heparin can be directly applied to clinical practice, but due to its lower anticoagulant activity, it requires approximately twice the dose of porcine heparin to achieve the same effect. There are signiffcant differences in structure and anticoagulant activity between bovine LMWH and porcine LMWH. Thus, if bovine LMWH is to be developed as a drug, it may need to be registered in accordance with the standards for new drugs.

该文介绍并分析了美国 FDA《cGMP 生产和过程控制相关法规问答》指南文件，通过其中 12 个与微生物控制相关的问答，从无菌生产工艺药品、非无菌药品中的不可接受微生物、药品微生物控制共性问题及眼用制剂无菌性 4 个方面，探讨加强药品生产过程中微生物控制的方法。对无菌工艺生产的药品，应关注非传统微生物污染、培养基模拟灌装试验频率和环境监测 ；对非无菌药品，应建立不可接受微生物的书面程序，并进行风险评估和控制 ；共性问题包括抑菌效力和局部消毒产品，不可利用抑菌剂降低药品的初始微生物负载并予以放行，局部消毒产品也应关注微生物污染风险 ；对眼用制剂，应确保其生产过程和有效期内的无菌性。最后，结合 ChP 2025 年版的制修订动态，提出了制定微生物控制策略的相关建议，以期提升国内药品的微生物控制水平，降低微生物污染风险。

A new synthetic process of iguratimod(1) was reported. Firstly, in the presence of aluminum chloride, the starting material 3-methylsulfonylamino-4-phenoxyphenyl methyl ether(2) reacted with acetyl chloride to generate N-(4-acetyl-5-hydroxy-2-phenoxyphenyl)methanesulfonamide(3). Then, the key intermediate N-(3-bromo-4-oxo6-phenoxy-4H-chromen-7-yl)methanesulfonamide(19) was synthesized by the addition-cyclization reaction of N,Ndimethylformamide dimethyl acetal/N-bromosuccinimide and 3. Compound 7 was obtained by amination of 19 with ammonium hydroxide. Finally, 1 was synthesized from 7 by formylation. The yield increased from 27.4％ to 33.0％ (based on 2), and the HPLC purity of the target 1 reached 99.9％ . The new synthetic process has the advantages of short steps, avoiding the use of flammable, explosive, and toxic chemical reagents, and mild reaction conditions, less side reaction, which is suitable for industrial production.

This study comprehensively evaluated the in vitro pharmaceutical properties and in vivo pharmacokinetic characteristics of sotalol hydrochloride scored tablets(80 mg). The tablets were split along the score line using manual splitting and a mechanical tablet splitter. The mass loss, weight variation, friability, and stability of the split tablets were systematically investigated. The similarity of dissolution profiles between the self-prepared preparations and the reference preparations(the whole and half tablets) was compared in four different dissolution media. A Beagle dog pharmacokinetic model was established to compare key pharmacokinetic parameters between the whole and half tablets. The results showed that both splitting methods achieved uniform tablet division, with mass loss less than 3.0％ , weight variation within 85 ％ - 115 ％ , and friability less than 1.0 ％ . After storage at room temperature for 90 d, the split tablets showed no significant changes in appearance, content, impurities, and dissolution compared to the freshly split tablets. The dissolution profiles of the half tablets were similar to those of the whole tablets. Pharmacokinetic data indicated that there was no statistically significant difference in tmax and t1/2 between the half and whole tablets(P>0.05). The AUC for half tablets was approximately 50％ of that for whole tablets. This study demonstrated that the test tablets could be split uniformly. The split tablets maintained stable quality, and the half tablets exhibited in vitro dissolution equivalence and a proportional pharmacokinetic relationship with the whole tablets in vivo, supporting the basis for clinical personalized dosing.