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。

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.

The droplet size distribution was measured by the laser particle size measurement system, while the spray pattern and plume geometry were measured by SprayVIEW laser imaging system. The spray performances of two kinds of suspension nasal sprays between the original drugs and the generic drugs were compared. Additionally, the consistency of spray performances between different batches of the samples from 4 companies(A, B, C, D) was analyzed in this study. The results showed that d(0.5) was in the range of 27 - 51 μm. The droplet size distribution results of the products from companies A and B, C and D were different. The intra- and inter-batch variabilities of the droplet size distribution of nasal sprays from companies A and D were less than those of the products from companies B and C, respectively. The spray area showed a signiffcant difference between the original drugs and the generic drugs. The plume geometry results of the products from companies A and B, C and D were similar. The cross section of the spray was nearly circular with elliptical rate of 1.13 to 1.41. The spray performance results of the products from the original drugs and the generic drugs were different. Therefore, it was necessary to strengthen the investigation on detection methods of the spray performances and comparison study of different products in the development of nasal spray products.

FDA 正式批准了2 款人用新型冠状病毒感染(COVID-19)mRNA 疫苗药物，分别为莫德纳(Moderna) 公司的 Spikevax，以及辉瑞/BioNtech 的Comirnaty，可作为该类技术里程碑意义的案例进行监管分析。COVID-19 mRNA 疫苗已 在国内紧急授权使用，但尚未正式获批上市，因此针对该类疫苗药物研发及监管的指导资料有限。文章基于FDA 公开的审 评资料，结合国内对疫苗的监管要求，对照解析mRNA 疫苗的审评特点，总结监管关注点，以期为我国mRNA 疫苗的发 展提供一定参考。

In situ gel is a novel formulation which is administered in solution and can rapidly occur phase transformation at the site of application to become semi-solid or solid gel. In addition, it can respond to the changes in external factors such as temperature, light, pH value, hydrophily/hydrophobicity, ionic strength. In situ gel has shown unique advantages in a variety of applications, including ophthalmic, nasal, oral, transdermal, injectable and vaginal routes, due to its excellent biocompatibility, bioadhesion ability, sustained- and controlled-release properties. In this paper, the advantages and disadvantages of traditional dosage forms and in situ gel are compared according to the characteristics of various routes of administrations. The research progress of in situ gel in above routes is introduced, and some approval in situ gel products are presented.

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.

Inflammatory bowel disease(IBD) is a chronic intestinal inflammatory disease with an increasing incidence rate year by year, but its etiology is still unclear. And there is a lack of well-targeted and safe therapeutic drugs. In recent years, probiotics have shown large potential as a potential treatment strategy for the prevention and treatment of IBD. This paper elaborates on the mechanism of probiotics in the treatment of IBD, summarizes common probiotic species used in the treatment of IBD, and looks forward to the application of probiotics, aiming to lay a foundation for the research on probiotics in the treatment of IBD.

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。

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.

Microneedles are a novel transdermal drug delivery method with the advantage of improving drug permeation efffciency and bioavailability. However, microneedle technology faces problems such as insufffcient hardness and poor drug delivery accuracy in actual clinical applications. Bionics is a scientific approach that constructs technical systems with specific functions by utilizing the functions and behaviors of biological systems in nature, it can effectively achieve innovative integration between systems, and provide new ideas for solving above problems. At present, bionic microneedles are widely applied in the medical field, such as assisting in wound healing, surgical operations, and physiological/pathological monitoring. This paper summarizes the researches on improving microneedle performance using bionics, and discusses the clinical development prospects of bionic microneedles to provide a new perspective for the future development of microneedle technology.

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.

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.

1,2-Dipalmitoyl-sn-glycero-3-phosphorylcholine(DPPC, 1) can be used not only as a pharmaceutical excipient, but also as an exogenous lung surfactant for the treatment of neonatal respiratory distress syndrome(NRDS). Glycerophosphatidylcholine(GPC, 2) reacted with palmitic acid(PA, 3) in the presence of 4-dimethylaminopyridine (DMAP) and dicyclohexylcarbodiimide(DCC) in DCM to yield 1. But it was found that an impurity was produced, which seriously affected the puriffcation of the product. After isolation and puriffcation, the impurity was conffrmed by MS and 1 H NMR to be 1,1'-methylene-bis(4-dimethylaminopyridinium) dichloride. Through replacing reaction solvent to acetonitrile and reducing the feeding molar ratio of DMAP from 3 to 1, the yield of the target product 1 was increased from 33.20％ to 49.18％ with purity of 99.92％ .

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.

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.

A dye ingress method was established to assess the package integrity of prefflled syringes and vials. On the basis of setting rational parameters as well as preparing negative and positive samples, the vacuum, negative pressure holding time and the processing method of the prefflled syringe packaging system were optimized, and the method was verified. The results showed that the sensitivity of this method for assessment the integrity of the prefilled syringe packaging system and the vial packaging system was 10 - 15 μm, and was better than those in the USP, EP and International Organization for Standardization under the same conditions. This method could effectively assess the integrity of the prefilled syringe packaging system and the vial packaging system, which provided a reference for establishing the test standard for the prefflled syringe packaging system and the vial packaging system by dye ingress method.

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.

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.

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。

Site-specific integration of large DNA fragments based on non-viral methods are widely used in gene therapy and cell therapy because of their low cost, large capacity, non-immunogenicity, and the ability to avoid genotoxicity and oncogene expression. According to the mechanism, non-viral methods can be classified into three types, DNA damage repair-, recombinase- and transposase-based site-specific integration technologies. All three non-viral DNA targeting methods can be combined with the clustered regularly interspaced short palindromic repeats(CRISPR) and CRISPR associated proteins 9(Cas9) technology to quickly and easily direct exogenous DNA to the target DNA region. In this study, the research progress of the three non-viral-based DNA targeting methods and their applications are summarized to provide new ideas for the development of more efficient cell therapy systems.

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

Using fluorene(2) as the starting material, it was chlorinated by trichloroisocyanuric acid to obtain 2,7-dichlorofluorene(3), which was acylated with chloroacetyl chloride to produce 2,7-dichlorofluorene-4-chloroethyl ketone(4). Then, α-(di-n-butylaminomethyl)-2,7-dichloro-4-fluorenylmethanol(5) was obtained via reduction, cyclization and amination by one-pot method. Finally, 5 was condensed with p-chlorobenzaldehyde to obtain benfluorenol(1), with an overall yield of 36％ and a purity of 99.4％ . The improved process used trichloroisocyanuric acid as the chlorinating agent, which improved the selectivity and safety of the reaction. The reduction, cyclization and amination were completed by onepot method, which reduced the reaction temperature, shortened the reaction cycle, improved production efficiency, and increased the yield from 60％ to 80％ . The improved process was simple to operate, low in production cost and suitable for industrial production.

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.

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.

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.

Four potential related substances were synthesized, namely 2-[(7R,11R)-2,3-dihydroxy-3,7,11,15- tetramethylhexadecyl]-3-methylnaphthalene-1,4-dione(related substance A), 1α-methyl-7α-[(7R,11R,E)-3,7,11,15- tetramethylhexadec-2-en-1-yl]-1α,7α-dihydronaphtho[2,3-b]oxirene-2,7-dione(related substance B), 2-[(7R,11R,E)-3- hydroxy-3,7,11,15-tetramethylhexadec-1-en-1-yl]-3-methylnaphthalene-1,4-dione(related substance C) and 2,5-dimethyl- 2-[(4R,8R)-4,8,12-trimethyltridecyl]-2H-benzo[h]chromen-6-ol(related substance D).Their structures were confirmed by 1H NMR and MS, which provided a reference for the quality control of vitamin K1.

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.

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.

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.

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 control the quality of dexmethylphenidate hydrochloride(1), possible impurities were traced and synthesized, including four impurities of 1, namely (±)-threo-2-phenyl-2-(piperidin-2-yl)acetic acid(impurity A), (±)-erythro-methyl-2-phenyl-2-(piperidin-2-yl)acetate(impurity B), (±)-threo-ethyl-2-phenyl-2-(piperidin-2-yl) acetate(impurity E), dimethyl 2,2'-(piperidine-1,2-diyl)bis(2-phenylacetate)(impurity G), and two intermediate impurities, namely (E)-4-methyl-N'-[2-oxo-1-phenyl-2-(piperidin-1-yl)ethylidene]benzenesulfonohydrazide(impurity α) and 2,2'-(hydrazine-1,2-diylidene)bis[2-phenyl-1-(piperidin-1-yl)ethan-1-one](impurity β). The structures of above six impurities were confirmed by 1H NMR, 13C NMR and MS, which could be used as reference substances for the quality control of 1, and provided references for isolation and purification of 1.

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。

This study aimed to investigate the cause of an unidentified peak that appeared ahead of the VP3 subunit peak during the purity analysis of adeno-associated virus(AAV) capsid subunits by capillary electrophoresis sodium dodecyl sulfate(CE-SDS) technique. Initially, a point mutation was introduced to the second start codon within the base sequence of the recombinant adeno-associated virus(rAAV) capsid protein’s VP3 subunit via PCR to generate a mutant rAAV. Subsequently, the relationship between this mutation and the unidentified signal peak was elucidated using CE-SDS technique. Additionally, the relative molecular weight and peptide analysis of the unknown peak was detected by LC-MS. The results indicated that if the VP3 subunit’s base sequence contain two initiation codons(ATG), the translation might start from the second initiation codon. And the expression product was a variant of the VP3 subunit(VP3'), which aligned with the unidentified signal peak observed in CE-SDS analysis. Consequently, this unidentified peak should be regarded as a AAV capsid subunit peak during the purity assessment of AAV capsid proteins.

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.