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
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2023 Volume 54 Issue 04   Published: 10 April 2023
  
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    Perspectives & Review
  • Perspectives & Review
    TAO Yuping, ZHAO Zhenyu, LI Youxin , SUN Kaoxiang, SHI Yanan
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Small interfering RNA(siRNA), a representative therapeutic tool for targeted therapy and precision medicine, can silence the expression of any disease-related gene through sequence-specific RNA interference(RNAi). However, its therapeutic prospects have historically been limited by short half-lives in vivo, difficulties in delivery, and safety concerns. Non-viral vector drug delivery has efficiently achieved siRNA delivery in vivo and silenced the target gene, becoming a successful strategy to overcome above limitations. Currently, several drugs are already in clinical trials, and four new siRNA-based therapies have been approved recently by the U.S. FDA, marking the beginning of a new era of targeted therapies. This review summarizes the recent development and application of siRNA-based non-viral vector delivery strategies and predicts the future development trend of siRNA drug research.
  • Perspectives & Review
    WANG Danyang, XU Tingting, CHEN Jianjun, QIU Yunliang
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Gene therapy is a new approach to treating diseases by altering gene expression in vivo, provides a new treatment strategy for tumors, rare diseases, and other refractory diseases. Gene therapy modifies the pathogenic genes of an individual through gene editing technology and relies on gene delivery vectors to improve the stability and targeting in vivo of genes. This review briefly describes gene therapy methods, introduces the development of viral and non-viral vectors for gene delivery and gene editing technologies in gene therapy combined with the current gene therapy products, and summarizes the safety issues of gene therapy in clinical practice.
  • Perspectives & Review
    LI Zixiang, YI Dong, CHEN Daijie, TAN Jun
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Selenium is one of the elements needed to sustain the normal physiological functions of the human organism. Moderate intake has a variety of functions, including antitumor, antioxidant, and immunological enhancement. Numerous probiotics are capable of converting inorganic selenium into organic selenium and selenium nanoparticles(SeNPs), which can reduce selenium toxicity and increase human absorption. With the dual effects of selenium and probiotics, selenium-enriched probiotics have significant effects on human health and have a broad marketing potential in the development of food and drugs. This review focuses on the fundamental research on the fermentation and bioactivity of selenium-enriched probiotics in recent years and introduces some of the current critical research on selenium-enriched probiotics.
  • Perspectives & Review
    GUO Meiyu, WANG Lu, QI Xiaodan
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Traditional therapeutic drugs have many shortcomings, such as poor stability, low uptake efficiency, high cytotoxicity and poor targeting ability. Therefore, safe drug delivery systems are needed to prolong drug circulation and exposure in vivo. New drug delivery systems based on red blood cells have gradually become ideal platforms for drug delivery due to their good biocompatibility, low immunogenicity and long circulation time. There are various types of drug delivery systems based on red blood cells, such as red blood cell membrane-encapsulated nanoparticle drug delivery systems and genetically engineered red blood cells. In addition, the functional modification of red blood cells can significantly enhance the targeting of red blood cell-based drug delivery systems to further develop and expand their applications in the treatment of various diseases. This review introduces the delivery methods of chemical drugs and vaccines using red blood cell-based carriers, focuses on bionic nano drug delivery systems and their targeting properties to various body positions. And the research progress of genetically engineered red blood cell-based strategy in recent years is summarized.
  • Perspectives & Review
    HUANG Lanyi, ZHANG Shu
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Hydrogel is a three-dimensional network polymer with good hydrophilic, flexible and swelling properties. Due to its good drug-loading property, hydrogel is widely used in the fields such as drug delivery, diagnosis, treatment, and tissue engineering. This paper reviews the classification of hydrogels, materials and performance improvement of hydrogels, the formation mechanism of hydrogels and cross-linking agents, by summarizing the recent literature on hydrogels at home and abroad. The development of hydrogels for drug delivery system is prospected. It is expected to provide some references for relevant researches.
  • Perspectives & Review
    ZHU Yangbin, CHEN Yirui, LING Fei, ZHONG Weihui
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Florfenicol is a kind of veterinary chloramphenicol broad-spectrum antibacterial drug, which is widely used in countries around the world due to its strong antibacterial ability. Since the molecular structure of florfenicol contains two chiral centers, the existing synthetic methods can be divided into chiral resolution and asymmetric synthesis. Chiral resolution is relatively unexpensive and has been industrialized, while asymmetric synthesis is greener and in line with the future development trend, but it is challenging. In this paper, the synthesis methods of florfenicol and its key intermediates are reviewed. The preparation methods of D-threo-p-methylsulfonylphenylserine ethyl ester, an intermediate of florfenicol, are described in detail, and different preparation methods including fluorination process are compared.
  • Paper
  • Paper
    CHEN Daopeng, JIN Xin, GAO Zizhen, YANG Xiangping, XU Xiangyang
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The related substance Ⅰ was detected by HPLC in midazolam, and it was found that the related substance Ⅰ gradually transformed into the related substance Ⅱ in the injection. According to the relative molecular weight determined by LC/MS, it was speculated that the related substance Ⅰ should be 8-chloro-4-ethoxy-6-(2- fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine, and the related substance Ⅱ should be 1-[4-chloro- 2-(2-fluorobenzoyl)phenyl]-2-methyl-1H-imidazole-5-carbaldehyde. This discovery was reported unprecedentedly. These two compounds were synthesized with midazolam as the starting material. Their structures had been confirmed by ESI-HRMS, IR and NMR. The prepared compounds were in consistence with the related substances Ⅰ and Ⅱ in the midazolam bulk drug and its injection by HPLC.
  • Paper
    ZHANG Yiming, RAN Qijun, CHENG Cheng, TANG Lei, WANG Jianta, ZHU Gaofeng
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    In order to perform the quality control of ursodeoxycholic acid, seven related substances were synthesized. 3,7-Dioxocholanoic acid, 7α-hydroxy-3-oxocholanoic acid, 7-oxolithocholic acid, 3-hydroxy-6-oxocholanoic acid, 3,6-dioxocholanoic acid, 3-oxocholanoic acid and 3β,7α-dihydroxycholanoic acid were synthesized from chenodeoxycholic acid, hyodeoxycholic acid, or lithocholic acid via oxidation, esterification, acylation and reduction. The yields were 68%, 17%, 74%, 60%, 76%, 70% and 15%, respectively. The chemical structures of above related substances were confirmed by NMR and HRMS.
  • Paper
    QIU Zhongxuan, WANG Dong, GUAN Lijun, XIN Feifei, ZHAO Meifa
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Suzuki-Miyaura coupling reaction was applied to synthesize the related substances of salbutamol sulfate for the first time. Three related substances, namely 4-(2-t-butylamino-1-hydroxyethyl)phenol(related substance B), 2,2'-dihydroxy-4,4'-di(1-hydroxy-2-t-butylaminoethyl)diphenyl ether(related substance F) and 4-(2-t-butylamino- 1-hydroxyethyl)-2-methoxymethyl phenol(related substance M), were synthesized through benzyl protection, Suzuki- Miyaura coupling reaction, addition reaction, nucleophilic substitution, Pd/C reduction with 5-bromo-2-hydroxybenzyl alcohol and p-bromophenol as the starting materials. The above method possesses the advantages of generality and high efficiency. The structures of related substances B, F and M were confirmed by HRMS, 1H NMR and 13C NMR.
  • Paper
    XU Jinhua, ZHAO Wenpeng, ZHAO Lili, CAO Yu, PENG Wei, LIU Zhong
    2023, 54(04): 545-553.
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The establishment of the fibroblast growth factor 21(FGF21)-Fc fusion protein in vitro activity test can be divided into binding assay at the protein level and biological assay at the cell level. This study established a homogeneous time-resolved fluorescence(HTRF) method to detect the binding activity of FGF21-Fc fusion protein and β-Klotho ligand protein. And the reporter gene cells were constructed independently to test biological activity. When the FGF21-Fc fusion protein binded with β-Klotho, the FGF receptor and the intracellular signal transduction were activated to further affect luciferase activity, which could be used to monitor and quantitatively measure biological activity indirectly. During the establishment process of the binding assay, the sample and ligand concentrations, dilution ratios of donor and acceptor, and incubation time were optimized comprehensively. And methodological verification was carried out to prove that the HTRF technology had good repeatability and specificity and this method could be used to detect the binding activity of FGF21-Fc fusion protein and β-Klotho. Later, the fetal bovine serum concentration, density of report gene cells, plate type, and cells in the plate form in bioactivity assay were optimized. And methodological verification was carried out to prove that the reporter gene method had good repeatability and specificity and this method could be used to test the biological activity of FGF21-Fc fusion protein. In this study, a quality control method for FGF21-Fc fusion protein was established, which provided a reference for analysis technology of drugs with the same activity detection difficulties, filling the gap at home and abroad.
  • Paper
    LI Jingyi, WANG Jie, WANG Rui
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    Nanoemulsification technology was applied to improve the solubility and oral absorption behaviors of the insoluble Chinese medicine curcumin(1), achieving an efficient therapeutic effect for colorectal cancer. The nanoemulsion loaded with 1 was prepared through high-shear emulsification. The observation of transmission electron microscopy showed that the 1 nanoemulsion was spherical, and its particle size was (98.79±1.08)nm. After in vitro simulated digestion, (71.03±2.93)% of 1 was still dissolved in the aqueous phase. Moreover, intestinal absorption and pharmacokinetic experiments in vivo revealed that the nanoemulsion could promote the intestinal absorption of 1, especially in the duodenum segment. The 1-loaded nanoemulsion also exhibited the pharmacokinetic characteristics of fast absorption and slow elimination, and the relative oral bioavailability of 1 was improved to 313.50%. In the orthotopic nude mouse models of colorectal cancer, 1 nanoemulsion could effectively inhibit the tumor growth after oral administration. The weight of harvested tumor tissue in the 1 nanoemulsion treatment group was about 23.91% of that in the phosphate buffer treatment group, indicating that 1 nanoemulsion had an excellent therapeutic prospect in treating orthotopic colorectal cancer.
  • Paper
    CHEN Huiting, LIU Kehai
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Using glycyrrhetinic acid(GA)-doxorubicin(1)-triphenylphosphine(TPP) as a model drug, a targeted mitochondrial delivery system, namely the hyaluronic acid(HA)-modification cationic liposomes(LP-G1T@ HA), was constructed by the film dispersion method. Moreover, its pharmacologically related properties and antitumor activity in vitro were evaluated. The results showed that the particle size and encapsulation rate of the LP-G1T@HA were (340.3±2.3)nm and (85.4±3.1)%, respectively, and it showed good in vitro serum stability and low hemolytic toxicity. In vitro cell experiments demonstrated that LP-G1T@HA significantly inhibited the proliferation of MCF-7 breast cancer cells, induced the mitochondrial permeability transition pore(MPTP) opening, and accelerated cell apoptosis, suggesting that LP-G1T@HA could be used as an efficient mitochondrial-targeted delivery system to achieve an efficient antitumor effect.
  • Paper
    BI Jiawei, LIU Jinxia, ZHAO Yumeng, LIU Yanhua
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    To improve the water solubility of meloxicam(1), its nanosuspension was prepared by ultrasonicassisted precipitation method. The formulation and process parameters were optimized by single factor test. The optimal formulation process was as follows: 0.2% of poloxamer 188 and 0.2% of hydroxypropyl methylcellulose(HPMC) were used as the combined stabilizers, the volume ratio of water to oil phase was 30∶1, the ultrasonic power ratio was 50%, and the ultrasonic time was 35 min. The particle size, polydispersity index(PDI) and ζ potential of the optimal 1 nanosuspension were 263.8 nm, 0.189 and–20.54 mV, respectively. After reconstruction of the freeze-dried powder of 1 nanosuspension, the particle size and PDI increased while ζ potential decreased compared with the 1 nanosuspension before lyophilization. The results of transmission electron microscopy(TEM) and X-ray diffraction(XRD) showed that 1 existed in the form of original crystal in the nanosuspension. The molecular dynamic simulation results showed that intermolecular hydrogen bonds were formed between the drug, poloxamer 188, and HPMC. The in vitro dissolution results showed that the dissolution rate and degree of 1 from the nanosuspension in pH 6.0 and pH 6.8 phosphate buffer solutions were significantly higher than those of the bulk drug and its physical mixture with the combined stabilizers.
  • Paper
    OU Cailing, CHEN Jingjing, WANG Qin, WANG Xiaofei
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    To improve the stability of ambroxol hydrochloride and clenbuterol hydrochloride oral solution, a full factorial design of experiment was used to analyze the influences of type and amount of sweeteners on stability of the title oral solution. The results showed that the lower amounts of the sweeteners used, the more stable the ambroxol hydrochloride and clenbuterol hydrochloride oral solution would be. And, formaldehyde in the sweeteners was a key substance that affected the stability of ambroxol hydrochloride. By optimizing the source and amount of sweeteners and reducing the content of formaldehyde in the solution, impurity contents in the title oral solution could be reduced. Meanwhile, a prediction model was established based on the experimental data of stability tests. It was predicted that the impurity E content in the self-made ambroxol hydrochloride and clenbuterol hydrochloride oral solution would reach 0.2% in about 3.64 years when the samples were stored at 25 ℃.
  • Paper
    LI Li, GU Xiangshuai, QIAO Fangxia, NIU Yang, YANG Jianhong
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Taking the initial tack, peeling strength, cohesion and comprehensive physical performance of the matrix as evaluation indicators, the types and amounts of the components of the blank matrix of the gel were screened and optimized by single factor test and Box-Behnken design-response surface methodology. The results showed that the optimal composition for the blank matrix of the composite traditional Chinese medicine cataplasm for external use was as follows: 6.14% of sodium polyacrylate NP700, 4.06% of sodium polyacrylate N500, 0.21% of aluminum glycinate and 24.05% of glycerin. The optimal composite traditional Chinese medicine cataplasm had a smooth appearance, good formability and viscoelasticity.
  • Paper
    LU Tingting, ZHANG Xin, YANG Hao, LIU Boming, LIU Qingliang
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Applying the concept of “quality by design”, an initial risk assessment of various formulation variables of alfacalcidol soft capsules affecting disintegration time was conducted. The potential high-risk variables, including gelatin type, the mass ratio of gelatin to glycerol to water, and the amount of titanium dioxide used as opacifier, were obtained from the risk analysis. Single factor tests were carried out to optimize these variables with commercially available alfacalcidol soft capsules as the control. The optimal soft capsules were prepared with gelatin(180LB8) in a 1∶0.30∶1 mass ratio of gelatin to glycerol to water, and each soft capsule shell contained 2.5 mg of titanium dioxide. The disintegration time of the self-made soft capsules stored under accelerated conditions for 1 month did not significantly change, which was close to the control soft capsules stored at the same condition.
  • Paper
    LI Wenhua, ZHAO Bingke, WANG Junze, CHEN Jinghua, QIU Lipeng
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    In this study, a gallic acid-modified chitosan hydrogel system was constructed, and its in vitro
    antibacterial capability, inhibition effects on bacterial biofilm and extracellular polysaccharides were investigated. Gallic
    acid modified chitosan(CS-GA) was synthesized by amide reaction, and the CS-GA hydrogel was formed by dissolving
    in water. The structure of CS-GA was confirmed by the infrared spectroscopy, ultraviolet spectroscopy, and 1H nuclear
    magnetic resonance(NMR) spectroscopy. Moreover, the grafting efficiency of gallic acid in CS-GA was (52.94±0.62)%,
    measured by UV-Vis. Then the inhibition effect of CS-GA on the bacterial biofilm and extracellular polysaccharides were
    investigated with Escherichia coli and Staphylococcus epidermidis as models. The inhibition rates of the CS-GA hydrogel at
    32 mg/mL against bacterial biofilm and extracellular polysaccharide of E. coli were (81.91±0.00)% and (29.57±3.00)%,
    respectively; while for S. epidermidis were (52.86±0.01)% and (37.14±0.31)%, respectively. The results indicated that
    the constructed GA-CS hydrogel showed good inhibition effects on bacterial biofilm and extracellular polysaccharides.
  • Paper
    LUO Jiajia, ZHOU Jing, XU Yunhui, GUO Yuhan, HUA Moli
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The volatile oils of hemp were extracted by steam distillation and the gas chromatography-flame ionization detection(GC-FID) method was established to determine the main components including β-caryophyllene(1), α-caryophyllene(2) and caryophyllene oxide(3) with n-tridecane(4) as the internal standard. The results showed that this method had good resolution and specificity. It was linear for 1 - 3 in the concentration ranges of 0.001 7 - 0.174 8, 0.001 7 - 0.170 0, 0.001 8 - 0.178 4 mg/mL, respectively. The detection limits of 1 – 3 were 0.087, 0.085, 0.180 μg/mL, respectively. The average sample recoveries(n=9) were 107.12%, 99.01% and 93.30%, with the RSDs of 2.33%, 1.14% and 1.61%, respectively. This method can be used for the determination of 1 - 3 in the volatile oils of hemp and provides a technical support for its quality control and medical application research.
  • Pharmaceutical Management & Information
  • Pharmaceutical Management & Information
    LIU Jianfeng, GU Donglei, LI Yingqi, WANG Xiaowen, HUANG Yuting, ZHENG Yiwei
    Abstract ( ) Download PDF ( )   Knowledge map   Save
  • Pharmaceutical Management & Information
    HU Xiaojuan
    Abstract ( ) Download PDF ( )   Knowledge map   Save
  • Pharmaceutical Management & Information
    YAO Bingcheng, ZHANG Huaxiang
    Abstract ( ) Download PDF ( )   Knowledge map   Save