主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA
Author Center Peer Review Editor-in-Chief Staff Login
Current Issue
2025 Volume 56 Issue 6   Published: 10 June 2025
  
  • Select all
    |
    Perspectives & Review
  • Perspectives & Review
    YAN Jingwen, ZHANG Panpan, CHEN Yuting , ZHANG Wei, , KONG Dezhi,
    Abstract ( ) Download PDF ( )   Knowledge map   Save
  • Perspectives & Review
    FANG Zeqing, LUO Huafei, ZHU Huiyong, HUANG Hemin
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    This review provides a systematic overview of the composition of styrene-isoprene-styrene triblock copolymer(SIS) hot-melt pressure-sensitive adhesives, including SIS thermoplastic elastomers, tackifiers, plasticizers, antioxidants, and fillers. Based on this, it details the preparation process and analyzes how coating and drying processes affect performance of hot-melt pressure-sensitive adhesives. Finally, this review summarizes current applications of SIS hotmelt pressure-sensitive adhesives as matrix materials to transdermal patches.
  • Perspectives & Review
    CHEN Ying, WANG Can, SHAO Hong, XU Weidong
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Antibody drug conjugates(ADCs) are biotherapeutic agents composed of a monoclonal antibody covalently linked to a cytotoxic payload via a chemical linker. Their unique structure combines the dual advantages of antibody-mediated targeted delivery and the potent cytotoxicity, demonstrating remarkable clinical efficacy in solid tumors, hematological malignancies and other therapeutic areas. ADCs are expected to play a pivotal role in future global drug development. Throughout the entire lifecycle of ADC development, manufacturing, and quality control, their binding affinity and biological activity critically influence therapeutic efficacy and safety. Comprehensive characterization of in vitro biological activity not only serves as the cornerstone for ensuring the clinical performance but also drives the resolution of current technical challenges and the advancement of innovative drug development. This review systematically discusses the current in vitro biological activity evaluation methods of ADCs, focusing on five functional modules based on the mechanism of ADCs: target binding activity, internalization efficiency, payload cytotoxicity, bystander effect, and Fcmediated functions, aiming to provide methodological references for ADC development and quality control.
  • Paper
  • Paper
    SUN Niubing, GU Xiu, WU Xingyu, HAN Bo, ZHANG Qingwei,
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Based on histone deacetylase 6(HDAC6) inhibitor SW-100 and HDAC inhibitor(compound 1) containing a benzothiadiazole dioxygen fragment as lead compounds, a series of HDAC6 inhibitor( Ⅰ a - Ⅰ b and Ⅱ a - Ⅱh) with benzothiadiazole dioxygen fragment were designed and synthesized by pharmacophore fusion strategy. Structures of the target compounds were confirmed by MS, 1 H NMR and 13C NMR. The enzyme inhibition activities of target compounds showed that the compound Ⅰ e exhibited superior inhibitory activity and selectivity towards HDAC6( Ⅰ e: HDAC6 IC50=1.4 nmol/L, HDAC1/6=10.0; SW-100: HDAC6 IC50=9.4 nmol/L, HDAC1/6=14.7). The molecular docking results showed that compound Ⅰ e can bind to HDAC6 protein well and interact with multiple amino acid residues. In the preliminary investigation of metabolic stability and safety, compound Ⅰ e showed minimal species differences and good metabolic stability in rat and mouse liver microsomes[t1/2(rat)=59.7 min, t1/2(mouse)=59.2 min]. Additionally, compound Ⅰ e showed low hERG inhibitory activity and weak antiproliferative effects on human neuroblastoma cells(SH-SY5Y cells), suggesting a low cardiotoxicity and good safety.
  • Paper
    XU Youyin, YOU Chang, MENG Xueling, XU Bixue, ZENG Xiaoping,
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An optimized synthetic process of bentysrepinine(1) was developed. Using methyl L-tyrosinate hydrochloride(2) as the starting material, the intermediate methyl N-benzoyl-L-tyrosinate(4) was synthesized by condensation with benzoyl chloride. Hydrolysis of 4 under alkaline conditions afforded N-benzoyl-L-tyrosine(6), which was reacted with L-phenylalaninol in the present of isobutyl chloroformate(IBCF) and N-methylmorpholine(NMM) to obtain N-[N-benzoyl-L-tyrosyl]-L-phenylalaninol(7), then the reaction of 7 with 2-chloro-N,N-dimethylethylamine hydrochloride provided the target 1 with an overall yield of 55.0% (based on 2) with HPLC purity of 99.0% . The improved process is stable and easy to operate, and produces less waste water, which is suitable for industrial production.
  • Paper
    ZHANG Fujian, ZHU Jinbo, WANG Lianjin
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    This study optimized the synthesis process of the antigout drug benzbromarone(1). Starting from 2-ethylbenzofuran(2) and 4-methoxybenzoyl chloride(3), 2-ethyl-3-(4-hydroxybenzoyl)benzofuran sodium(16) was prepared by Friedel-Crafts acylation, demethylation, and phenolate formation in the presence of FeCl3/AlCl3 catalyst supported on activated carbon. The aqueous solution of 16 was selectively brominated under the catalysis of phosphotungstic acid to obtain the target product 1, with the total yield of 66.0% (based on 2) and the purity of 99.91% . The improved product has high purity, low cost, and is suitable for industrial production.
  • Paper
    WANG Wenyi, PAN Haibo, LIU Jiajia, LIU Jinnai, ZHANG Fuli, ZHAO Chuanmeng
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    2-[[1-[(4-Bromo-1-naphthyl)methyl]imidazo[5,4-b]pyridin-2-yl]sulfanyl]-2-methylpropanoate methyl ester, an imidazopyridine derivative, is an antigout drug candidate targeting urate transporter(URAT1 receptor) with uric acid-lowering effects. This candidate drug exhibits polymorphism. Four crystalline forms with industrial potential were yielded by adjusting solvents and temperatures during the crystallization process in this study. Identification methods for each crystalline form were established through characterization using powder X-ray diffraction, thermogravimetric analysis, and differential scanning calorimetry(DSC). Furthermore, accelerated stability studies confirmed that all four crystalline forms remained stable under 40 ℃ and relative humidity of 75% conditions. Photostability tests showed that crystalline formsⅠ and Ⅲ were insensitive to light, while crystalline forms Ⅱ and Ⅳ exhibited significant crystalline form transformation. Solubility tests demonstrated that crystalline form Ⅲ had significantly better solubility than the other crystalline forms in aqueous media(25 ℃ pure water and hydrochloric acid of pH 1.2). Comprehensive analysis suggested that crystalline form Ⅲ has the potential for development as a superior drug polymorph.
  • Paper
    ZHANG Linli, LI Yizhi, CHENG Quan, LIU Li ,
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    To establish an in vitro thyroid module for thyroid pharmacodynamic research, this study constructed thyroid organoids derived from adult mouse stem cells and analyzed the stem-like cell populations of the organoid. First, the culture medium was optimized based on cell population and characteristics of the organoid as indicators. Hematoxylin and eosin(H&E) staining was used to display the histocellular structure of organoids; while immunohistochemistry(IHC) and immunofluorescence(IF) staining were employed to identify the expression of thyroid specific proteins. Meanwhile, the electrochemiluminescence assay was used to assess the secretory functions of T3 and T4. Subsequently, the stem cell gene markers in organoids were profiled by single cell RNA sequencing(scRNA-Seq), the expression of stem cell protein markers were verified by IF staining, and the cell proportion of stem cell expression was quantified by flow cytometry. The results showed that thyroid organoids derived from mouse adult stem cell were successfully established by optimizing the culture medium. Mature organoids contained thyroid follicles, and expressed characteristic molecular markers and secreted thyroid hormones. The results of scRNA-Seq revealed an enriched subpopulation of p63+ Isl1+ Sox2+ cells with stem cell properties. The results of IHC and flow cytometry analyses further confirmed the presence of the above stem-like cell populations in organoids and their markers expression. In conclusion, the established thyroid organoids serve as a reliable in vitro model for exploring thyroid development and pathogenesis.
  • Paper
    LI Zidan, YAN Youming, LU Yuehan, WU Mingfei, MENG Jie
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    To investigate the effects of score design on the quality of scored tablets, five types of scored tablets were selected as models, and the effects of tablet shape, shape and depth of score line, tablet hardness on the partitioning capability of different specifications and different tablets were evaluated with tablet weight variation, mass loss, content uniformity, and dissolution/release as evaluation indicators. The results showed that capsule-shaped tablets were easier to be split than circular tablets. When the long-to-short axis ratio of the capsule-shaped tablet was less than 2, tablet weight variation could be improved by increasing the score line depth(approximately 0.5 mm). The recommended hardness range for sustained-release scored tablets was between 90 N and 130 N to maintain the integrity of the pellets; the recommended hardness range for orally disintegrating tablets was between 30 N and 50 N to meet the requirement of disintegration time limit within 60 seconds. Low dose(specification ≤ 10 mg) scored tablets should pay attention to the content uniformity of intact tablets(A+2.2S ≤ 7.0) and the mass loss( ≤ 0.8 % ) after segmentation to control the accuracy of tablet splitting. Manual and mechanical splitting showed no significant differences in various indicators of the segmented parts, fully complying with the requirements of Chinese Pharmacopoeia 2020 Edition and the related guidance. These findings validated the rationality of the model drug score design and provided guidance for scored tablets development.
  • Paper
    SU Tong , TONG Yu , JIANG Qieying , OUYANG Qi , LIAO Zhenggen
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    In this study, baicalin(1)-imperatorin(2) co-amorphous system(1-2-CAS) was prepared by spray drying method. Subsequently, powder X-ray diffraction(PXRD) and differential scanning calorimetry(DSC) were used to confirm its amorphous state. The effects of a small amount of sodium dodecyl sulfate(SDS) on the equilibrium solubility of 1 and 2 were investigated by shaking flask method. The effect of 1-2 physical mixture on the critical micelle concentration of SDS was investigated by pyrene fluorescence probe method. The inhibitory effects of SDS on the nucleation and crystal growth rates of 1 and 2 crystals were monitored by UV-Vis spectroscopy. The dispersion time and agglomeration degree of the samples were evaluated by dispersion tests. And a contact angle analyzer was employed to measure the static contact angle of the samples. The results showed that small amount of SDS could significantly enhance the dissolution rates of 1 and 2 in 1-2-CAS by improving wettability and dispersion without altering the solubility or crystalline properties of the insoluble drugs, which provided a reference for optimizing the dissolution of co-amorphous systems containing two poorly soluble drugs.
  • Paper
    QI Muge , LI Gengsheng , GUO Zhonghua , WANG Xiaobing , MA Shuang , WEI Yage
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An HPLC method was established for the simultaneous determination of the contents of nine components(thymine, protocatechuic acid, vanillic acid, daidzin, scopoletin, genistin, daidzein, glycitein, and genistein) in child compound endothelium corneum(CCEC) chewable tablets. This method was simple with good accuracy and repeatability, which provided a comprehensive basis for the quality control of CCEC chewable tablets. Meanwhile, the effects of CCEC chewable tablets on the rat models of functional dyspepsia(FD), food stagnation and anorexia were investigated. The results showed that CCEC chewable tablets could enhance the activities of cholecystokinin(CCK)-8, motilin(MTL), and pepsin in FD rats; increased the absorption rate of D-xylose, gastric pH, and pepsin activity in food stagnation rats. It also improved the rates of gastric emptying, intestinal motility, and pepsin levels in anorexia rats. The pharmacological research results indicated that CCEC chewable tablets had a significant therapeutic effect on functional dyspepsia, which provided a certain pharmacological basis for its clinical application.
  • Paper
    XIAO Yan , ZHANG Jing, LIU Chunxia , FENG Jinfen , ZHAN Kun
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    A discriminative in vitro release testing(IVRT) method for metronidazole(1) gel was developed and applied to evaluate the consistency between the self-developed generic preparation and the reference listed drug. Through systematic investigation of critical parameters including dose amount, receptor medium composition, sampling intervals, and release membrane selection, robust IVRT conditions were established. The developed IVRT method and quantitative analytical method were validated. The in vitro release behaviors of the reference listed drug and the self-developed generic preparation were evaluated. The results of statistical analysis using the Mann-Whitney U test showed that the 90% confidence interval of the release rate between above two formulations was 95.88% - 102.34% . Both formulations exhibited sustained steady-state drug release characteristics within 4 h(R2 ≥ 0.97) with cumulative release amount exceeding 70% . These results indicated that the in vitro release behavior of the test and reference 1 gel was basically equivalent.
  • Paper
    LI Tiantian, SHI Zhuowei, DONG Shanshan, WANG Can, SHAO Hong,
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    This study explored the feasibility of using the human promyelocytic leukemia(HL-60)/nuclear transcription factor kappa B(NF-κB ) reporter gene method to detect the pyrogen content in recombinant human type Ⅱ tumor necrosis factor receptor-antibody fusion protein. According to the “In vitro Pyrogen Test(Reporter Gene Pyrogen Testing Method)” in the General Chapter <3309> of the 2020 Edition of ChP First Supplement, products from 4 manufacturers were selected to investigate potential interference with the HL-60/NF-κB reporter gene assay. Then, the HL- 60/NF-κB reporter gene assay was applied to detect pyrogen content. The results showed that there was no interference from the tested products in pyrogen detection. Furthermore, the pyrogen contents in 16 batches of products from the four manufacturers were below the limit standard value. Therefore, this method is suitable for pyrogen detection in recombinant human type Ⅱ tumor necrosis factor receptor-antibody fusion protein, which provides a reference for pyrogen testing in biopharmaceutical products.
  • Paper
    ZHAO Xingxing , LU Honghua, DU Yuhe , LIU Jifa , LI Futing , HAO Guizhou
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    A GC-MS method was established for the determination of the potential genotoxic substances such as cyclopentanecarbaldehyde(2), diethyl ethylphosphonate(3) and 2-diethoxyphosphorylacetonitrile(4) in ruxolitinib phosphate(1). The ZB-624plus capillary column(0.25 mm×30m×1.4 μm) was used, and the measurement was performed in multi reaction monitoring(MRM) mode. The results showed that it was linear for 2 - 4 in the range of 30 - 180 ng/mL. The limits of quantification for 2 - 4 were 14.67, 14.95 and 14.75 ng/mL, respectively, and the recoveries were 99.63% , 103.73% and 102.60% , respectively, which provided a reference for the quality control of 1.
  • Paper
    LI Ye, ZHANG Bing, SHEN Tiantian, YANG Min, LIN Huangjing
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Medium borosilicate ampoules containing propofol emulsion injection were exposed to three experimental conditions: accelerated testing[0, 3, and 6 months under at 40 ℃ and 75% relative humidity(RH)], long-term testing(6, 12, and 36 months at 25 ℃ and 60% RH) and extraction testing(121 ℃ for 1 h), respectively. The migration and leaching of elements(Al, Si, B) in glass ampoules were determined by ICP-MS. The inner surface morphology of the test samples (neck of ampoule, lower part of the body, bottom of ampoule) was observed by SEM. The size of the eroded area, and the area of the erosion zone were measured and calculated. The results of ICP-MS and SEM demonstrated a time-dependent increase in Al, Si, and B leaching under both accelerated and long-term conditions. Erosion could be observed at the bottom of the ampoule body, with accelerated testing inducing a significant expansion of the affected area. Comprehensive analysis indicates that propofol emulsion injection will have a certain degree of erosion effect on the inner surface of medium borosilicate ampoules.
  • Paper
    GUO Yanyan, QIU Yiting, HUANG Wansha, ZHANG Xiaochun, JIANG Yan
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    A comprehensive method combining Raman spectroscopy, thermogravimetric analysis(TGA), infrared spectroscopy(IR), and inductively coupled plasma mass spectrometry(ICP-MS) was developed to analyze the inorganic components in pharmaceutical halogenated butyl rubber stoppers. Titanium dioxide and alumina in the rubber stoppers could be accurately identified by Raman spectroscopy, calcium carbonate in the rubber stoppers could be accurately detected by TGA combined with IR, and the inorganic components in the rubber stoppers could be predicted by ICP-MS. This method can be used for the analysis of inorganic components in pharmaceutical halogenated butyl rubber stoppers.
  • Pharmaceutical Management & Information
  • Pharmaceutical Management & Information
    MENG Han, SUN Yujie , LIU Junjie, WANG Le , XU Jing
    Abstract ( ) Download PDF ( )   Knowledge map   Save
  • Pharmaceutical Management & Information
    LIU Yue , GUO Wen,
    Abstract ( ) Download PDF ( )   Knowledge map   Save