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  • Chunyan LÜ, Xiaoqing HOU, Wenyu CUI, Wenjun ZHANG, Wenqian WANG, Rui HAN
    Chinese Pharmaceutical Journal. 2024, 59(16): 1488-1494.

    In recent years, in the process of drug research and development, insoluble drugs are faced with the problem of low bioavailability and poor absorption effect. Drug nanocrystals have attracted much attention due to their nano size and unique physical and chemical properties, which can effectively increase drug solubility and permeability, and have advantages such as low dosage of excipients, high drug load and few adverse reactions. However, instability limits their further development. Multieffect stabilizers can significantly improve their stability through steric hindrance, electrostatic repulsion and solvation. The author reviews the main characteristics and limitations of drug nanocrystals, the classification of multi-effect stabilizers and their applications in vivo and in vitro by reviewing and sorting out relevant literature, in order to provide reference for the research and development of drug nanocrystals.

  • Ying WANG, Yuanxi LIU, Mingrui SHEN, Tingting ZHOU, Xianrui ZHANG, Yi HE, Hongyu JIN, Feng WEI, Shuangcheng MA
    Chinese Pharmaceutical Journal. 2024, 59(16): 1453-1459.

    OBJECTIVE To develop the limited standard and supporting detection methods of commonly used pesticides in Lycium barbarum L. (L. barbarum). METHODS In previous research, the “the Principle of Conversion of Limit Standards of Traditional Chinese Medicine in <GB 2763 national food safety standard-maximum residue limits for pesticides in food>” have been drafted. In this research, the L. barbarum was used as the research object to study the conversion scope, risk assessment, detection methods and conversion judgment principle. RESULTS A method for the determination of 13 pesticide residues in the L. barbarum was established by using acetonitrile extraction and HLB column purification. And the GC-MS/MS and LC-MS/MS technology were used to detect the pesticide residues. In addition, the maximum residue limit of 13 pesticides in L. barbarum was finally formulated by sample determination. CONCLUSION The specific implementation steps are provided for the conversion of GB 2763 standard to traditional Chinese medicine standard in this study, and it is of great significance for promoting the connection between planting and circulation supervision of L. barbarum.

  • Yuhui GUO, Fengyuan PAN, Mei LI, Xiaohan TANG, Changcheng ZHANG, Le TONG
    Chinese Pharmaceutical Journal. 2024, 59(16): 1513-1521.

    OBJECTIVE To investigate the ameliorative effect of Guifu Dihuang Wan (GFDHW) on intestinal lipid absorption dysfunction in aging mice and its potential mechanisms. METHODS Twenty-six SPF male C57BL/6J mice aged 11 months were raised to 21 months and divided into an aging model group (Model group) and a GFDHW group (1.17 g·kg-1). The GFDHW group received medication via feed administration for 3 months, with free access to water during the administration period, while the Model group was fed normal feed and had free access to water. Weekly changes in body weight were recorded for each group of mice, and specimens were collected at 24 months of age. Nine SPF male C57BL/6J mice aged 8 months were used as the youth control group (Con group) and were acclimatized for 1 week before specimen collection. Prior to specimen collection, all groups of mice were fasted for 24 hours, and 0.2 mL of olive oil was administered by gavage to each group of mice at the end of the fasting period, followed by gavage of 0.2 mL of semi-solid nutrient solution 30 minutes before specimen collection. Small intestine propulsion tests were conducted to assess the small intestine motility of each group of mice. Biochemical reagent kits were used to measure the serum levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in each group of mice. Transmission electron microscopy was used to observe changes in the number of lipid droplets in intestinal epithelial cells of each group. The calcium cobalt method was used for alkaline phosphatase staining to detect intestinal alkaline phosphatase (IAP) activity in each group of intestines. Hematoxylin-eosin (HE) staining was used to observe the morphology of intestinal epithelia in each group. Immunohistochemical staining was performed to detect the expression of Olfm4, Lgr5, PCNA, Notch1, Hes1 and Villin in the small intestines of each group of mice. Western blot analysis was conducted to determine the expression levels of lipid absorption-related molecular proteins in the small intestines of each group of mice. RESULTS Compared with the Con group mice, the Model group mice exhibited faster weight loss, decreased small intestine motility, increased serum TG, TC, and LDL levels, and increased number of lipid droplets in intestinal epithelial cells. The GFDHW group mice showed improved small intestine motility and decreased serum TG, TC, and LDL levels. HE staining revealed disordered arrangement and fracture of small intestinal villi, shortened villus length, decreased crypt depth, and reduced crypt numbers in Model group mice, whereas the GFDHW group mice exhibited orderly and continuous arrangement of small intestinal villi, increased villus length, higher crypt depth, and increased crypt numbers. The immunohistochemical results showed that compared to the Con group mice, the expression of Olfm4, PCNA, Notch1, Hes1, and Villin proteins in the small intestine of the Model group mice decreased, while the levels of these proteins increased in the GFDHW treated group mice. Western blot analysis revealed that compared to the Con group mice, the expression of CD36, FATP4, SR-BI, ACAT2, FABP1 and MTTP proteins in the small intestine of the Model group mice decreased, whereas the levels of these proteins increased in the GFDHW treated group mice. CONCLUSION GFDHW improves lipid absorption function in aging mice by upregulating Notch1 expression, promoting differentiation of intestinal stem cells into absorptive cells, and increasing the expression levels of related molecular proteins in the lipid absorption pathway.

  • Yuanxi LIU, Ying WANG, Mingrui SHEN, Haonan WANG, Tingting ZHOU, Hongyu JIN, Shuangcheng MA, Feng WEI
    Chinese Pharmaceutical Journal. 2024, 59(16): 1460-1465.

    OBJECTIVE To screen the commonly used pesticides in Dendrobium officinale to understand their pesticide residues, and explore the establishment of a method for determining the transformation of pesticide residues in Dendrobium officinale and the development of limit standards in accordance with the requirements of GB 2763 Food Safety Standards for Maximum Residue Limits of Pesticides in Food and the Chinese Pharmacopoeia. METHODS LC-MS/MS methods were used to screen and risk assess 6 transformation pesticides in 53 batches of Dendrobium officinale, and the pesticide registration status and the maximum residue limit standards for Dendrobium officinale (dry) in GB 2763 were used to determine the indicators for the transformation of pesticides. RESULTS The pesticides in 53 batches of Dendrobium officinale were analyzed. The transformation pesticide were confirmed in accordance with GB 2763 and the requirements of the Chinese Pharmacopoeia 2020 Edition, and a method for determining the transformation of pesticide residues in Dendrobium officinale was established, along with the development of limit standards. CONCLUSION This study screened 40 commonly used pesticides and 6 transformation in 53 batches of Dendrobium officinale, established a method for determining the transformation of pesticide residues in accordance with GB 2763, and developed limit standards. This study is helpful for understanding the risk of pesticide residues in Dendrobium officinale, regulating the use of pesticides during its cultivation process, and improving its quality standards.

  • Chengjun HE, Zhao GENG, Lian ZHONG, Donglin GU, Hongyu JIN, Ying WANG, Feng WEI, Shuangcheng MA, Lei YANG, Yan GOU
    Chinese Pharmaceutical Journal. 2024, 59(16): 1470-1477.

    OBJECTIVE To establish a method for simultaneous determination of registered pesticides, prohibited pesticides, and proposed new prohibited pesticide residues in Fritillaria Medicinal Herbs, and propose reference limits. METHODS The detection method for 95 pesticide residues in Fritillaria Medicinal Herbs was established using GC-MS/MS and LC-MS/MS. The prepared samples were extracted with acetonitrile and then purified with the QuEChERs method. A total of 70 batches of samples were detected by the established method. RESULTS According to the GB 2763 conversion guidelines, imidacloprid and avermectin in Fritillaria Medicinal Herbs should be converted to the maximum residue limit (MRL) standards. Additionally, reference limit values are proposed for the 18 prohibited pesticides that were previously suggested for addition. CONCLUSION The study of Fritillaria Medicinal Herbs aims to offer guidance and inspiration for the transformation of traditional Chinese medicine standards and the expansion of the list of banned pesticides. It also provides a reference for the regulatory policies and technological advancements related to pesticide residue management in Fritillaria Medicinal Herbs and other traditional Chinese medicines.

  • Huawei ZHAO, Yuefang SHEN, Wuxiao ZHOU, Yinghua NI, Yanhong LI, Yangyang SUN, Jing MIAO
    Chinese Pharmaceutical Journal. 2024, 59(16): 1545-1550.

    OBJECTIVE To investigate the efficacy and safety of different preparations of intravenous immunoglobulin (IVIG) for Kawasaki disease treatment in children. METHODS A retrospective analysis of medical records of pediatric Kawasaki disease patients at our institution in recent three years was conducted. Patients were divided into preparation A group and preparation B group based on the type of IVIG preparations used. Both groups received IVIG (2 g·kg-1) in conjunction with aspirin therapy following Kawasaki disease diagnosis. Changes in body temperature, white blood cell count, platelet count, C-reactive protein levels, IVIG cost, length of hospital stay, and adverse events were compared. RESULTS According to the drug labeling, there are certain differences between preparation A and preparation B. Preparation B exhibited a significantly shorter duration of fever resolution compared with preparation A (P<0.005), and at the first temperature test after infusion, the body temperature of preparation B group was significantly lower than that of preparation A group (P<0.05). Furthermore, preparation B demonstrated a more significant reduction in white blood cell count following treatment (P=0.010). In terms of hospital stay duration and IVIG monotherapy costs, preparation B had significantly shorter hospital stay (P<0.05) and lower per-unit IVIG expense (P<0.001). No significant differences were observed between the two groups in terms of adverse events, including rashes, infusion interruptions due to high fever, liver injury, and coronary dilation. CONCLUSION There is significant difference in efficacy between different preparations of intravenous immunoglobulin in the treatment of Kawasaki disease in children, but the safety is similar.

  • Chunmei TAN, Qi XIAO, Ting DONG, Juan WANG, Juanjuan WANG, Ying WANG, Hongyu JIN, Cuifeng FANG
    Chinese Pharmaceutical Journal. 2024, 59(16): 1466-1469.

    OBJECTIVE To establish a method for the transformation of some commonly used pesticide limit standards in Chrysanthemi Flos based on ‘GB 2763 National Food Safety Standard-Maximum Residue Limits for Pesticides in Food’. METHODS The indexes of Chrysanthemi Flos (dry) in GB 2763 were sorted out, and the quasi-transformation pesticides were determined as pymetrozine, imidacloprid, boscalid and fluazinam according to the transformation principle. The UPLC-MS/MS method was used to establish the transformation method of Chrysanthemi Flos, and the methodological verification was carried out. RESULTS The four pesticides had good linear relationship in the range of 1-50 ng·mL-1, the correlation coefficients were 0.999 9, the average recovery was 77.9%-95.5%, and the RSD was 1.7%-6.8%. The overall detection rate of the samples was 60%, and the pesticide with the highest detection rate was imidacloprid. The maximum detectable amount was 1 mg·kg-1 (imidacloprid), and the results did not exceed the maximum residue limit specified in GB 2763. The risk assessment system of pesticide residues in traditional Chinese medicine was used to evaluate the chronic risk of the four pesticide limit values to be transformed. The results showed that the chronic risk of fluazinam was greater than 1, and the chronic risk quotients of the other three pesticides were less than 1. Therefore, fluazinam is not converted temporarily, and only pymetrozine, imidacloprid and boscalid are converted. CONCLUSION The three limit standards of pymetrozine, imidacloprid and boscalid in Chrysanthemi Flos were transformed. The established limit standard transformation method is simple and accurate, which is of great significance for standardizing the use of pesticides and medicinal safety in the process of chrysanthemum planting.

  • Hanshuang DENG, Xiaoling LI, Xin WANG, Lang ZHANG, Jinjuan SUN
    Chinese Pharmaceutical Journal. 2024, 59(15): 1429-1437.

    OBJECTIVE To establish the HPLC fingerprint of Forsythiae Fructus and develop a multi-component quantitative analysis method based on quantitative analysis of multi-components by single-marker(QAMS). METHODS The fingerprints of 47 Forsythiae Fructus samples from four provinces, including Henan, Shandong, Shanxi and Shaanxi, were established by high performance liquid chromatography (HPLC), while their similarity was evaluated. Chemical pattern recognition of Forsythiae Fructus was studied by hierarchical cluster analysis (HCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The content of forsythoside B, forsythoside A, hyperin, arctiin, phillyrin and phillygenin were determined by using QAMS, and the differences of samples from different producing areas were analyzed. RESULTS The fingerprints of 47 Forsythiae Fructus samples were established with similarities ranged from 0.785 to 0.989, and a total of 30 common peaks were identified. According to HCA, the samples were divided into three groups. OPLS-DA analysis can effectively distinguish Forsythiae Fructus from several producing areas (Q2>0.5). There was no significant difference in the content of 6 components in 47 batches of samples by QAMS and external standard method (ESM) (P>0.05), but there was significant difference in the content of active components in samples from different origin (P<0.01). The average contents of forsythoside B, forsythoside A, hyperin, arctiin, phillyrin and phillygenin in samples from different provinces were, Henan(4.50、20.58、0.52、2.39、7.46、1.76 mg·g-1), Shandong(0.90, 9.26、0.36、1.39、3.84、3.87 mg·g-1), Shanxi(0.82、8.74、0.29、1.16、2.64、1.75 mg·g-1), Shaanxi(5.18、55.10、0.88、3.36、13.11、9.25 mg·g-1). CONCLUSION The chemical composition of Forsythiae Fructus samples from different locations was similar, but the origin factors had a significant effect on the content of active ingredients, and the samples from Shaanxi province had the highest content. The HPLC fingerprint combined with the simultaneous determination of multi-component content analysis method established in this study is stable and reliable. The fingerprint combined with the chemical pattern recognition can provide a basis for the identification of origins and quality evaluation of Forsythiae Fructus.

  • Hai LIAO, Xinyi YU, Xue HUANG, Tian ZHANG, Huige QUAN, Yuchen LI, Jiayu ZHOU
    Chinese Pharmaceutical Journal. 2024, 59(15): 1393-1399.

    OBJECTIVE To construct molecularidentification of Fritillaria taipaiensis and its relatives based on Indel marker. METHODS One hundred and three chloroplast genomes of 13 Fritillaria species were downloaded from GenBank and were subsequently used to screen Indel marker based on sequence alignment. Then, in accordance with the conserved upstream and downstream of Indel marker, a pair of specific primers was designed accordingly, by which a method including routine PCR and electrophoresis was constructed. Furthermore, the specificity, sensitivity, and optimal reaction temperature of the method were assessed. RESULTS One deletion of 137 bp was found in the accD-psaI spacer region of F. taipaiensis chloroplast genome according to the multiple sequence alignments, which was defined as the Indel marker for F. taipaiensis. The constructed method exhibited high specificity due to the fact that only F. taipaiensis exhibited a band of 302 bp after routine PCR and electrophoresis. The limit of detection for F. taipaiensis DNA template was 0.239 ng·μL-1, and the optimal melting temperature (Tm) value was 58 ℃. CONCLUSION This accurate, quick and cost-affordable method provides not only identification of F. taipaiensis and its related species, but also technical reference for identification of other traditional medicines.

  • Ziying ZHANG, Lingzhi WU, Ni YIN, Zhenxin WANG
    Chinese Pharmaceutical Journal. 2024, 59(15): 1361-1365.

    Thrombocytopenia is a disorder characterized by a decreased platelet count in the peripheral blood, which can be caused by various congenital and acquired diseases. Currently, thrombopoiesis-promoting drugs used for thrombocytopenia primarily include recombinant human interleukin-11 (rhIL-11), recombinant human thrombopoietin (rhTPO), and thrombopoietin receptor agonist (TPO-RA). Hetrombopag is an innovative oral non-peptide TPO-RA that has been approved for treating chronic adult primary immune thrombocytopenia (ITP) with inadequate response to glucocorticoids and immunoglobulin, as well as severe aplastic anemia (SAA) with poor response to immunosuppressive therapy in China. Clinical studies have demonstrated that hetrombopag is safe and well-tolerated in ITP and SAA patients. Currently, there is an ongoing phase Ⅲ clinical trial investigating the efficacy of hetrombopag in managing chemotherapy-induced thrombocytopenia (CIT). This article provides a review on the research progress of hetrombopag in treating thrombocytopenia, aiming to offer valuable insights for clinical practice.