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.

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.

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.

Reactive oxygen species(ROS) are byproducts of cellular redox metabolism. Excessive ROS can lead to oxidative damage of DNA, proteins and lipids, thereby exacerbating the genetic instability of cancer cells and promoting tumor initiation and progression. Peroxiredoxin 1(PRDX1), a key member of the peroxidase family, plays a pivotal role in maintaining intracellular ROS balance, effectively protecting cells from ROS-induced damage. Simultaneously, PRDX1 acts as a molecular chaperone in various malignancies, exhibiting dual roles in either promoting or inhibiting tumor growth. In recent years, numerous PRDX1-targeting candidate drugs have demonstrated significant antitumor effects both in vitro and in vivo, confirming PRDX1 as a potential target for cancer therapy. This review summarizes recent advances in understanding the mechanisms of PRDX1 as a tumor treatment target, as well as the development of antitumor natural products targeting PRDX1.

Dimetridazole(1) is a nitroimidazole antibacterial agent and an antiprotozoal veterinary drug. The traditional batch methylation for the synthesis of 1 has issues such as low yield, abundant disubstituted impurities, and high safety risks. In this study, 1 was prepared through a continuous flow reactor, which effectively reduced potential risks in the methylation reaction and increased the yield from 53％ (reported in the literature) to 73％ . Meanwhile, four related substances of 1 were discovered and synthesized, namely 1,2-dimethyl-4-nitro-1H-imidazole(3), 1,2,3-trimethyl-5- nitroimidazolium monomethyl sulfate(4), and a mixture of N-methyl-N-(2-methylamino-2-nitrovinyl)acetamide(5) and N-methyl-N-(2-methylamino-1-nitrovinyl)acetamide(6), which provided some references for the quality control of 1. In addition, it was found that when ammonia was used in the work-up of the methylation reaction, the quaternary ammonium salt 4 could be demethylated into the target product, offering a new approach to turning waste into valuable product.

随着人工智能、集成电路、生物医药等前沿研究的持续进步，药品先进制造数字孪生愈发受到关注。目前，数字孪 生技术已在制药行业实现了某些场景应用，并在优化布局、提升产品质量、降低成本等方面发挥积极作用，但其技术要求 以及合规考量仍需深入分析。文章围绕药品先进制造数字孪生的挑战和关注要点进行探讨，就进一步推动生物医药产业高 质量发展以及国际化进行了展望，并在技术设计和实践方面提出建议，以期为药品先进制造的科学监管以及新质生产力的 发展提供一定参考。

Teduglutide(1) exerts its physiological effects by binding to glucagon-like peptide-2(GLP-2) receptors on the intestinal and digestive tract walls. Clinically, it is used to treat short bowel syndrome. In light of the current situation where only an expensive original product with limited accessibility is available on the domestic market, this study aims to develop a more efficient production method. To achieve this, small ubiquitin-related modifier protein was fused with 1 for intracellular soluble expression in Escherichia coli. The results showed that the target peptide reached a productivity of over 800 mg per liter of fermentation broth, with a purification yield of approximately 46％ and a purity exceeding 99％ . The LC-MS/MS analysis confirmed that relative molecular weight and amino acid sequence of the peptide were consistent with the theoretical predictions. This research offers a simple, low-cost, high-yield approach for 1 production, laying a foundation for future large-scale manufacturing.

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.

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.

口服混悬剂是为吞咽困难患者设计的一种非均相液体制剂，较其他口服制剂加入了更多种类的功能性辅料来维持体 系的稳定性及适口性，故其质量研究与控制难度大、潜在的安全性风险高。文章通过调研不同药品监管机构规定、指导原则、 药典等文件并结合药品审评经验，全面阐述如何开展该剂型的质量研究与控制，强调了易被忽略的问题，以期为业界开发 高质量的口服混悬剂提供参考。

Recombinant human granulocyte colony-stimulating factor(1) is clinically used to treat neutropenia caused by chemotherapy or radiotherapy in cancer patients. When expressed in Escherichia coli, 1 predominantly accumulates as inactive inclusion bodies. So, the low yield of inclusion body denaturation and refolding limits the overall process yield. In this study, soluble expression of 1 was achieved by employing a fusion expression strategy with the small ubiquitin-related modifier protein, with an expression level of 2.19 g/L. Further steps including extraction, enzymatic cleavage, clarification, anion exchange chromatography, cation exchange chromatography, and ammonium sulfate precipitation yielded 1 with a purity of 99.3％ and a recovery rate of 44.2％ . The structure and function of the self-produced 1 were confirmed through HPLC retention time comparison, mass spectrometry, peptide mapping, disulfide bond localization, and in vitro biological activity assays. Finally, a 50 L scale-up test demonstrated the feasibility of industrial-scale manufacturing for this process. This study provides a robust foundation for the industrialization and subsequent structural optimization of 1.

Oligonucleotide drugs have been utilized in the prevention and treatment of various diseases. To enhance their stability and facilitate transmembrane delivery, lipid nanoparticles(LNPs) are commonly employed as carriers. However, the poor stability of miRNA-LNPs results in stringent storage requirements, limiting their broad application. Therefore, this study investigated the effects of formulation and process parameters on miRNA-LNPs physical stability, using particle size and encapsulation efficiency as key indicators. The results indicated that various phospholipids contributed to the physical stability of LNPs, among which PEGylated phospholipids effectively preventing LNPs aggregation. The phase transition of water directly destroyed the LNPs structure, and the combination of cryoprotectant sucrose and PEGylated phospholipids could effectively resist the damage caused by water phase transition to the LNPs structure. By elucidating the mechanisms by which structural materials and water phase transitions affect miRNALNPs physical stability, this study introduced cryoprotectants as a novel strategy to improve the physical stability of oligonucleotide drug-loaded LNPs. These findings provide valuable insights for optimizing LNP-based formulations, thereby strengthening the clinical applicability of small nucleic acid therapeutics.

To enhance the solubility and dissolution rate of epalrestat(EP), a cocrystal of EP and benzamide(BAM), as well as its inclusion complex with hydroxypropyl-β-cyclodextrin(HP-β-CD), were prepared using a mechanical ball milling method. The preparation conditions for both the EP-BAM cocrystal and its inclusion complex were optimized. Structural characterization was performed using powder X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. The solubility performance was evaluated through saturation solubility experiments and in vitro dissolution tests were also carried out. The results showed that the solubility of the EP-BAM cocrystal increased by 1.08- fold compared to EP, while that of the EP-BAM/HP-β-CD inclusion complex increased by 11.53-fold. The results of in vitro dissolution tests showed that both the cocrystal and the inclusion complex exhibited superior dissolution rates and amounts compared with the physical mixture. The EP-BAM cocrystal and the EP-BAM/HP-β-CD inclusion complex significantly improve the solubility and dissolution rate of EP, providing an effective strategy to enhance its bioavailability.

文章探讨氘代药物相较于原型药物化合物专利的自由实施可能性，为药企开发氘代药物的侵权风险评估提供参考。 首先，简要梳理了我国专利侵权判定规则体系，概括了目前实践中原型药物化合物专利中权利要求和说明书的撰写方法， 最后结合氘代药物的特点，综合分析撰写方式对于氘代药物自由实施的可能影响。而评估氘代药物自由实施的可能性，一 方面需依据侵权判定的步骤和原则，另一方面需综合考量氘代药物相较于原型药物所具备的未揭示效果。

A HPLC method was established for the simultaneous determination of sodium chondroitin sulfate(2), vitamin B1(3), and vitamin B6(4) in compound cerebroprotein hydrolysate tablets(1), and the content uniformity was also investigated. Chromatographic separation was performed on a Hypersil BDS C18 column(4.6 mm×250 mm, 5 μm) using gradient elution with 0.02 mol/L sodium heptanesulfonate solution as mobile phase A and acetonitrile as mobile phase B. The column temperature was set at 35 ℃ , with an injection volume of 20 μL. The detection wavelengths were set at 200, 246, and 291 nm for compounds 2, 3, and 4, respectively. The methodological research results showed that the established method exhibited strong specificity, good linearity, repeatability, and accuracy. The sample determination results showed that the content and content uniformity of the three components in 1 from different manufacturers were significantly different, indicating the necessity for enhancing its quality control measures.

Cagrilintide(1) is a long-acting lipidated analogue of amylin, and its compound preparation with semaglutide, known as CagriSema, has demonstrated a weight reduction effect of up to 22.7％ in the latest phase Ⅲ clinical trials. However, the long amino acid sequence of 1 poses challenges for its synthesis and purification. In this paper, using Rink Amide AM resin as the carrier, Fmoc-protected amino acids as raw materials, ethyl cyanoglyoxylate-2-oxime/N,N'- diisopropylcarbodiimide as condensation reagents, and trifluoroacetic acid system as the lysis solution, the reduced crude peptide was synthesized by a solid phase peptide synthesis(SPPS) method from the C-terminus to the N-terminus of C20 diacid according to the amino acid sequence of 1. The intramolecular disulfide bonds were subsequently formed through iodine oxidation. The crude peptide was purified by RP-HPLC, affording a purified product with a purity of 98％ and a total yield of 26％. Additionally, this study explored and optimized the preparation process parameters, providing valuable insights for industrial production of 1.

An ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for the determination of dictamnine(1) and fraxinellone(2) in rat plasma. A UPLC HSS T3 chromatographic column(2.1 mm×50 mm, 1.8 μm) was used, and the analysis was carried out in the gradient elution mode with acetonitrile as mobile phase A and water(containing 0.1％ of formic acid) as mobile phase B. Positive ion mode detection and multiple reaction monitoring mode were used for quantitative analysis, with midazolam as the internal standard. The results showed good linearity for 1 and 2 in the range of 2 - 2 000 ng/mL. The extraction recovery rates of 1 and 2 were above 79.5％ , the precisions were less than 15％ , and the accuracies were 87.3％ - 109.8％ . In pharmacokinetic studies in rats, after gavage administration(2 mg/kg) or sublingual administration(0.1 mg/kg), the cmax of 1 were (1 382.4±129.6) and (382.6±118.9)ng/mL, with t1/2 of (1.5±0.2) and (2.3±0.5)h, respectively; the cmax of 2 were (57.5±2.2) and (742.6± 109.7)ng/mL, with t1/2 of (2.7±1.0) and (2.1±0.5)h, respectively. The bioavailability values of 1 and 2 were 68.1 ％ and 7.6％ , respectively. This established method provides a reference for its clinical use.

A centrifugal assisted liquid-liquid extraction combine with gas chromatography method was established for the determination of 17 related substances in sodium valproate(1) sustained-release tablets. The HP-FFAP column (0.32 mm×30 m×0.25 μm) and the hydrogen flame ionization detector were used with programmed temperature. The flow rate was 3.0 mL/min, the inlet temperature was 220 ℃ , and the detector temperature was 300 ℃ . The results showed that the established method could effectively separate 17 process impurities and degradation impurities, with a detection limit of about 0.25 μg/mL(0.005 ％ ). The impurities 2-methylvaleric acid and 2-methyl-2-ethylvaleric acid were detected in 1 sustained-release tablets by this method. This method solves the problem of difficult detection caused by material swelling and inability to dissociate in 1 sustained-release tablets and enables accurate determination of the related substances, providing a reference for the quality control and standard improvement.

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.

Cytotoxicity tests were conducted to evaluate the biosafety of medical polyurethane(PU) products. In this study, cytotoxicity tests of PU products mainly composed of bis(4-isocyanatocyclohexyl)methane(HMDI) and poly(tetramethylene ether)glycol(PTMEG) were conducted. The cytotoxicity of the PU products, raw materials and additives in the formulations were tested respectively according to the MTT method. The results showed that PU had no acute systemic toxicity, but the cell viability of PU was less than 50％, which indicated a cytotoxic potential. This laboratory prepared a small-batch of PU samples using the same formulation as commercial products, which passed acute systemic toxicity tests but exhibited only 8％ cell viability. After acetone cleaning, the cell viability increased to 60％ . The cell viabilities of the formulations containing HMDI and the additives such as chain extenders, antioxidants, light stabilizers and catalysts were more than 70％ in the cytotoxicity test, indicating no cytotoxicity. However, the cell viability of PTMEGcontaining formulations was less than 70％ , with viability decreasing as concentration increased, indicating that PTMEG might be the primary cause of PU cytotoxicity. It is recommended to adjust the proportion of PTMEG or replace it with polyols exhibiting superior biosafety performance in PU products, and optimize the cleaning process during production to ensure the biosafety of PU.

药品集中带量采购制度是发挥主动战略性购买作用、完善药品价格形成机制、规范药品流通秩序、减轻患者用药负担、 推动医药行业高质量发展的重要举措。为研究我国药品集中带量采购制度中存在的具体问题，文章检索了自 2019 年 1 月 1 日至 2024 年 1 月 31 日中国知网发布的有关我国药品集采问题的全部中文文献，梳理问题清单，并基于卫生系统宏观模型 形成问题系统，分析药品集采存在问题的层级结构和主次关系，为其进一步高质量发展提供一定的建议。

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.

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.

新药研发合作模式成为我国各大制药企业共同关注的话题。文章在改进原有竞合博弈范式基础上，采用复杂中介模 型分析了我国医药制造板块上市公司的博弈型研发合作对制药企业新药研发效率的促进机制。得出 2 条结论 ：①博弈型研 发合作有助于加快制药企业关键核心技术突破，从而显著提升制药企业新药研发效率 ；②不同博弈型研发合作的收益分配 模式，将对制药企业新药研发效率产生异质性影响。同时，提出了“市场均分型”和“股权收益型”2 种高绩效新药研发 合作模式，以期为我国制药企业突破关键核心技术、提高新药研发效率提供一定参考。

In order to meet the regulatory requirements for halide identification of pharmaceutical rubber stoppers(mainly chlorinated and brominated rubber stoppers) in packaging material changes and generic drug research and development, a rapid and accurate method based on pretreatment of ignition residue and ion chromatography detection was established. After ignition and ashing, residual ions in samples were extracted with water. The Dionex IonPac™ AS19 column was used, with 20 mmol/L potassium hydroxide solution as eluent, at a flow rate of 1 mL/min, column temperature of 30 ℃ , and injection volume of 25 μL. The results showed that it was linear for chloride and bromine ions in the range of 2 - 100 μg/mL, with satisfactory recovery and strong method specificity. The method was applied to determine 16 batches of halogenated butyl rubber stoppers from different manufacturers, and the determination results were completely consistent with the formulations claimed by the manufacturers. This simple, rapid, and accurate method enables effective identification and quantitative detection of halides in pharmaceutical stoppers, providing reliable technical support for packaging material changes of marketed drugs, generic drug packaging screening, and quality control of rubber stoppers.

As an emerging precision particle manufacturing technology, microfluidic technology harnesses the unique microfluidic phenomena in microscale environments to achieve continuous and reproducible production of micro/ nanoparticles. This review systematically summarizes the structural design principles and operational characteristics of common microfluidic channels, elaborates on recent advances in particle-based drug delivery systems, and highlights its advantages in controlling particle size, manipulating structures, and enhancing process efficiency. Furthermore, this review explores industrialization strategies, technical challenges, and future development directions of microfluidic technology, aiming to serve as a reference for the efficient preparation of micro/nanoparticle-based drug delivery systems.

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.

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.

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.

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.

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。

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.

The production environment for sterile pharmaceuticals plays a crucial role in fields such as drug manufacturing, directly impacting product quality and safety. In accordance with the latest domestic and international regulations and guidelines, this article introduces the environmental monitoring performance qualification(EMPQ) process for sterile pharmaceutical production environments. It focuses on cleanroom EMPQ procedures and risk assessment methods, and demonstrates the overall transition from EMPQ to environmental monitoring(EM) through specific examples. The aim is to provide a scientific basis for continuous optimization of sterile production environment monitoring in enterprises, ensuring more stable and safer product quality.

As an emerging transdermal drug delivery technology, microneedles can bypass the hepatic firstpass effect, effectively reducing the pain associated with traditional subcutaneous injections and realizing minimally invasive and painless drug administration. Polymer microneedles, characterized by their excellent mechanical properties and biocompatibility, can accurately penetrate the stratum corneum to create microchannels, significantly enhancing the efficiency of transdermal drug delivery. They have found widespread application to diabetes management, dermatological treatments, and vaccine delivery. This review emphasizes the analysis of matrix materials utilized in the preparation of various types of polymer microneedles, and discusses the application of polymer microneedles with different matrix materials to vaccine delivery, dermatological treatment and diabetes management, while also addressing the specific applications of these materials and highlighting the challenges and future development trends in this field.

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.

Based on the concept of quality by design, using the commercially available formulation Linzess® as the reference preparation, Box-Behnken design-response surface methodology was used to optimize the formulation of linaclotide capsules with the dissolution rate at 10 min as the evaluation index. The optimized formulation was as follows: selecting microcrystalline cellulose pellet core CP-305(with a particle size of approximately 400 μm), the amount of adhesive HPMC at 0.8％ (0.96 mg per capsule), and the ratio of calcium chloride to leucine of 3 ∶ 1(respectively 1.8 mg and 0.6 mg per capsule). Three batches of self-made preparations were prepared according to above final formulation for validation. The results showed that the content and content uniformity met the requirements. In various pH media, the dissolution rate of three batches of self-made capsules exceeded 85％ at 10 min, demonstrating consistent quality with the reference preparation.

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.

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.

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。