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  • Fang TIAN, Xin-yi DONG, Chong DU, Ya-juan GAO, Xiao-ping PU
    Chinese Journal of New Drugs. 2023, 32(6): 618-624.
    Objective:

    To explore the neuroprotective effect of acteoside (ACT) on mouse model of MPTP-induced Parkinson's disease (PD) and its mechanism.

    Methods:

    The PD mouse model was established by intraperitoneal injection of MPTP. The experimental mice were randomly divided into control group, model group and ACT group (100 mg·kg-1), which were administrated by gavage for 14 d. After administration, behavioral evaluation and biochemical detection were performed to evaluate the neuroprotective effect of ACT on PD mice. Two-dimensional electrophoresis, mass spectrometry and Western blot were used to further explore the anti-PD mechanism of ACT.

    Results:

    After prophylactic administration of ACT, the pole climbing time of MPTP-induced PD mice was significantly shortened, swimming test score was improved, suspension duration was prolonged, and hind limb tension test score and cylinder test score were decreased. ACT could effectively improve the activities of SOD, CAT, and GSH-Px in the substantia nigra and striatum of MPTP-induced PD mice and reduce the content of MDA. The results of two-dimensional electrophoresis and Western blot showed that the expression of biliverdin reductase B (BLVRB) increased in the substantia nigra and striatum of PD mice induced by MPTP, while the expression of BLVRB decreased significantly after the administration of ACT.

    Conclusion:

    ACT has neuroprotective effect on MPTP-induced PD mice, and its underlying mechanism may be related to the decrease of BLVRB expression and anti-oxidative stress of ACT.

  • Qian LIU, Yu-fei FENG, Meng-jie QI, Dong-sheng YANG, Hao-yue GUAN, Jian-zhao NIU
    Chinese Journal of New Drugs. 2023, 32(6): 572-575.
    Objective:

    To establish the first batch of national reference standard of rivaroxaban.

    Methods:

    The structure of rivaroxaban was confirmed by IR, NMR and LC-MS spectroscopy. The purity of rivaroxaban was determined by HPLC. Moreover, moisture and residual ignition were determined. The content of rivaroxaban was calculated by mass balance method.

    Results:

    The structure of rivaroxaban was confirmed. The content of the first batch of national reference standard of rivaroxaban was assigned as 99.6%.

    Conclusion:

    The first batch of national reference standard of rivaroxaban can be applied for the identification and content determination of rivaroxaban and its related preparations.

  • Jin LI, Shang-chen YAO, Chang-qin HU
    Chinese Journal of New Drugs. 2023, 32(6): 629-637.
    Objective:

    To establish a method for determination of polymer impurities in penicillin sodium for injection.

    Methods:

    Penicillin sodium was dissolved by water to prepare penicillin polymer stock solution. High performance size exclusion chromatography method (HPSEC) and column switching-LC/MSn method were used to separate and deduce the weak retention impurities in polymer impurity solution and the specificity of HPSEC method was evaluated. A RP-HPLC method for polymer analysis was established with a C18 column, using gradient elution by the mixed solution [phosphate buffer solution (pH 3.4)-methanol (72∶14)] and acetonitrile, and the RP-HPLC method was validated.

    Results:

    4 polymers, their isomers, one dimer degradation and some small molecular impurities were identified in the polymer impurity solution. Polymer impurities were liable to be co-eluted with small molecular impurities by HPSEC method, which resulted in poor quantification accuracy and specificity. 3 indicative polymer impurities were detected by RP-HPLC method with effective specificity, including 2 dimers produced by different polymerized patterns.

    Conclusion:

    HPSEC cannot effectively control the polymer impurities of penicillin sodium for injection. The established RP-HPLC method has good specificity and high sensitivity for the determination of impurities in penicillin sodium polymer for injection.

  • Ying-ying ZENG, Ai-wei SONG, Yue LIU, Hong-mei YUAN
    Chinese Journal of New Drugs. 2023, 32(6): 553-559.

    Based on the patent data of Scutellariae Barbatae Herba, this paper analyzed the current research situation of its industrial chain, aiming to provide relevant suggestions for its patent application and product development. The patent application of Scutellariae Barbatae Herba in China mainly experienced three stages: the slow development period, rapid development period and recession period. The number of patents is large, but the authorization rate is low. Individuals and enterprises are the main innovation entities of patent applications, and product development basically surrounded Scutellariae Barbatae Herba's efficacy, mainly focusing on downstream drugs, health food and other aspects, with less development in the middle and upper streams. Under such status, China should strengthen technical innovation of the whole industry chain and encourage collaborative innovation of industry, university and research, promote the combination of basic research and market application, provide theoretical support for the short board products, promote the transformation of scientific and technological achievements, and contribute to the innovation and upgrading of Scutellariae Barbatae Herba industry chain.

  • Ting-ting SHAO, Xiao-hua KONG, Jing JIN, Fan-cui MENG, Wei LIU
    Chinese Journal of New Drugs. 2023, 32(6): 610-617.
    Objective:

    To investigate the mechanism of compound AG-881 on inhibiting IDH1R132H mutant protein by molecular dynamics method.

    Methods:

    The activated IDH1R132H protein structure and inactivated AG-881-IDH1R132H protein structure were constructed respectively and placed in a stereoscopic box. Molecular dynamics simulations were carried out on each system for 100 ns. The protein conformations of different systems were compared, and hydrogen bond analysis, energy analysis and principal component analysis (PCA), etc. were performed.

    Results:

    Substrate α-KG could stabilize IDH1R132H protein in the activated closed conformation. After AG-881 acted on the allosteric site of the protein at dimer interface, it made IDH1R132H in the open conformation of inactive state. In this process, amino acid residue Gln277 participated into the binding of AG-881. At the same time, hydrophobic occupation and hydrogen bond contributed mainly to the binding of AG-881 to IDH1R132H. In addition, halogen bond also played a certain role.

    Conclusion:

    Molecular dynamics simulation can be used as an effective aid for allosteric inhibitor design, and the potential mechanism of AG-881 inhibiting IDH1R132H activity can be studied, which can further provide theoretical guidance for the development of new drugs targeting IDH1 mutant proteins.

  • Yi-hao LI, Yi-yang TENG, Ya-qun ZHANG, Zhuang QIAN, Wen-yuan HU, Xiao-qun ZHONG, Jing HU, Xiao-jun CHEN, Zhen-long YAN, Rui-nan PENG, Ya WANG, Hui LI, Jian-ya GE, Cheng-xian MIAO, Wei SHAO, Jian-jun LV, Toko OHIRA
    Chinese Journal of New Drugs. 2023, 32(6): 598-604.

    Toxicologic pathology is one of the most valuable disciplines contributing to the advancement of animal and human health. The gold standard of the toxicologic pathology evaluation in toxicity studies during nonclinical safety evaluation of drugs is considered to be the histopathological examination of paraffin-embedded, hematoxylin and eosin-stained tissue sections. Digital toxicologic pathology, artificial intelligence (AI), and in particular machine learning (ML) are globally disruptive, rapidly growing sectors of technology whose impact on the field of histopathology is quickly being realized. The development and application of increasing numbers of algorithms in the histopathological field have demonstrated that AI pathology platforms are now poised to truly impact the future of digital toxicologic pathology, precision medicine, and personalized medicine. However, as with all great technological advances, there are implementation and adoption challenges. The development of AI and ML, application of AI in toxicologic pathology, application of ML in digital toxicologic pathology, and impact of AI on digital toxicologic pathology were reviewed in the paper, in order to provide some references for applying AI and ML in toxicologic pathology in China.

  • Zhen-long YAN, Yi-yang TENG, Ya-qun ZHANG, Zhuang QIAN, Yan-chuan LI, Wen-yuan HU, Xiao-qun ZHONG, Jing HU, Xiao-jun CHEN, Yi-hao LI, Rui-nan PENG, Ya WANG, Hui LI, Jian-ya GE, Cheng-xian MIAO, Jian-jun LV, Toko OHIRA
    Chinese Journal of New Drugs. 2023, 32(6): 583-588.

    With the rapid research and development of cellular therapy products, new stem cell-derived cellular therapy products are constantly being developed, but only few relevant guidance documents to assist the design of studies for non-clinical safety evaluation have been published. Stem cell-derived cellular therapy products not only come from different sources, but also have different safety factors and potential risks of ectopic tissue formation, uncontrolled biological distribution, immunogenicity and tumorigenicity, etc. Different stem cell-derived cellular therapy products bring great challenges to non-clinical studies. The paper gives a brief overview of the types of stem cells and general principles for the non-clinical safety evaluation of stem cell-derived cellular therapy products, focusing on the animal selection, experimental design and tumorigenicity study, in order to provide some references for non-clinical safety evaluation of stem cell-derived cellular therapy products in China.

  • Xin LI, Ting LI, Fei-fei SUN, Ye TAO, Xin JIANG, Chen-jing WANG, Yu CAO
    Chinese Journal of New Drugs. 2023, 32(6): 560-566.

    New cancer cases are increasing year by year, which has become the focus of drug research and development. Based on the summary of clinical trials of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibody drugs in China, combining with the status of clinical trial registration, this paper analyzes the significance and problems of data disclosure.

  • Yuan WANG, Ming-ming KANG, Jun-jun WANG, Xiao-wen LI, Liang-zhu WEN
    Chinese Journal of New Drugs. 2023, 32(6): 589-597.

    Glucagon-like peptide-1 (GLP-1) analogues have been widely used in the treatment of diabetes and obesity, and multi-receptor agonists that combine GLP-1 analogues with other intestinal hormones such as glucose-dependent insulin-stimulating peptide (GIP) and glucagon (GCG) are in clinical development. Compared with GLP-1 analogues, multi-receptor agonists can exert multiple physiological effects and have better effects in controlling blood glucose and reducing body weight with fewer side effects, which are expected to be a new therapy for diabetes and obesity. In this paper, we reviewed the development of intestinal hormone multi-receptor agonists, summarized their design ideas and clinical manifestations, and provided reference for the development of multi-receptor agonists.

  • Dong WANG, Fei-fan YANG, Bao-feng GUO
    Chinese Journal of New Drugs. 2023, 32(6): 638-642.
    Objective:

    To improve the quality standards of Mongolian medicine Shashen Zhike Decoction Powder.

    Methods:

    TLC method was used to establish the identification of Bistortae Rhizoma and Shikonin, and the identification of Glycyrrhizae Radix et Rhizoma was revised. The content determination of glycyrrhizic acid was established by reversed phase HPLC.

    Results:

    The TLC identification methods resulted in clear spots of Bistortae Rhizoma, Shikonin and Glycyrrhizae Radix Et Rhizoma, without interference for the negative control. Glycyrrhizic acid had good linear relationship in the range from 92.90 to 1 161.25 ng (r=0.999 9). The average recovery was 102.57%, and the RSD was 1.85% (n=9).

    Conclusion:

    The method is simple, specific, stable and repeatable, and can be used for the quality evaluation and control of Shashen Zhike Decoction Powder.