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  • Du-juan XU, Meng-ya LIU, Gai-zhi LIU, Bang-rong CAI
    Chinese Journal of New Drugs. 2021, 30(13): 1207-1212.

    Andrographolide (AG) has been found extensively pharmacological activities such as anti-inflammatory, anti-tumor, anti-virus, anti-HIV, hepatic protection, etc. However, the poor solubility with low oral bioavailability of AG limits the clinical application. New formulations of AG using advanced techniques have been developed to improve these disadvantages. In this review, we summarizes the recent advancement of AG formulation studies, providing references on novel formulation development and clinic translation of AG.

  • He-nian YANG, Su-hui WU, Han-bing LI, Gen-lin LI
    Chinese Journal of New Drugs. 2021, 30(13): 1213-1219.

    Acorus calamus was first published in “Shen Nong's Materia Medica”. It is a traditional Chinese medicine for resuscitation and is widely used in prescriptions for the treatment of closed syndrome. In view of the exact clinical efficacy of calamus and the continuous discovery of new pharmacological activities and effective ingredients, in recent years, it has attracted wide attention in China and abroad and has become one of the hot research Chinese medicine varieties. However, the current edition of “Chinese Pharmacopoeia” stipulates the traditional physical and chemical identification of calamus and the determination of the total content of volatile oil. It is still difficult to reflect and directly relate the characteristics of calamus's multiple clinical functions with multiple complex components. The current quality markers of traditional Chinese medicine have pointed out the development direction and research ideas for the establishment of quality standards in line with the characteristics of traditional Chinese medicine. This article summarizes and analyzes the chemical components and pharmacological effects of calamus by consulting literature, and based on the definition of quality markers: The “five elements” of validity, uniqueness, transmission and traceability, measurability and prescription compatibility are used to predict and analyze the quality markers of calamus. The literature review found that the volatile components of Acorus calamus, especially the asarone components, can be used as the quality markers of this drug, providing a scientific basis for its complete quality control.

  • Mi-ya ZHANG, Liang CHEN, Hai-yan PANG, Hong YANG
    Chinese Journal of New Drugs. 2021, 30(13): 1220-1226.
    Objective:

    To combine the chemotherapy and photodynamic therapy in one system, the micelles (ID-M) that co-loaded the photosensitizer indocyanine green (ICG) and the chemotherapeutic drug doxorubicin (DOX) were prepared and characterized. The anti-tumor effects of ID-M in vitro were further investigated.

    Methods:

    An ultrasound dialysis method was used to prepare the micelles containing ICG and DOX (ID-M), while the single-encapsulated ICG micelles (I-M) and the single-encapsulated DOX micelles (D-M) were prepared using the same method as the controls. The particle size, Zeta potential, encapsulation efficiency and drug release behaviors of the micelles were measured. In addition, the anti-tumor effects and mechanism of ID-M in 4T1 cells were investigated.

    Results:

    The average hydrated diameter of ID-M particles was 80.4 nm with negative charge, and the coefficient of the particle size dispersion was 0.252 (<0.3). The encapsulation efficiency of ICG and DOX in ID-M were 92.5% and 96.8%, respectively. The results of the temperature warming testing under irradiation of ID-M solution reached (36.5±1.1) ℃. The release experiment of ID-M in vitro showed a significant sustained-release effect. Cell experiment proved that the uptake of 4T1 cells for ID-M was nearly 2 times higher than that for free drugs. The IC50 of ID-M inhibiting the growth of 4T1 cells with irradiation was 0.72 μg·mL-1, which was 3.6-fold lower than that of free ICG/DOX. Before light exposure, ID-M was mainly located in the lysosome. However, after light exposure, the ROS levels in the cells were increased due to the existence of ICG in ID-M, which damaged the lysosomal membrane and made DOX in ID-M enter to the nucleus to play a chemotherapeutic effect.

    Conclusion:

    In this study, the micelles (ID-M) with synergistic antitumor effects of phototherapy and chemotherapy were successfully prepared.

  • Ya-qin ZHEN, Ya-jing ZHI, Meng WANG, Wei TIAN, Jing-mei MA, Li-ying NIU
    Chinese Journal of New Drugs. 2021, 30(13): 1227-1235.
    Objective:

    To establish the UPLC fingerprints and multi-components content determination method of Cistanches herba formula granules and ultrafine granular power, and to provide a basis for their quality evaluation.

    Methods:

    The separation was achieved by using a ACQUITY UPLC BEH C18 (100 mm×2.1 mm, 1.7 μm) column via gradient elution with the mobile phase consisting acetonitrile and 0.1% phosphoric acid water. The flow rate was 0.3 mL·min-1 and the detection wavelength was set at 235 nm; the column temperature was 35 ℃ and the injection volume was 1 μL.

    Results:

    The UPLC fingerprints of Cistanches herba formula granules and ultrafine granular power were established, in which 10 common peaks were determined, and 6 components of geniposidic acid, caffeic acid, echinacoside, acteoside, tubuloside A, and isoacteoside were identified. The contents of these 6 components were determined. Using the developed method, the components were well separated, and had wide linear ranges with good linear relationships. The stability, repeatability and recovery rate met the requirements. Using cluster analysis and principal component analysis methods, Cistanches herba formula granules and ultrafine granular power can be distinguighed and identified.

    Conclusion:

    The UPLC fingerprints combined with multi-components content determination method are simple, accurate, and reproducible. It can quickly identify the formula granules and ultrafine granular power of Cistanches herba and evaluate their internal quality, providing a method reference for improving the quality control of formula granules and ultrafine granular power of Cistanches herba.

  • Xiao-na SHI, Zhi-ying ZHANG, Li-shuang WANG, Long-shan ZHAO
    Chinese Journal of New Drugs. 2021, 30(13): 1236-1241.
    Objective:

    To establish a liquid chromatography-tandem mass spectrometry method (LC-MS/MS method) for determination the contents of 5-methyl isoquinoline sulfonic acid (impurity A) and 5-ethyl isoquinoline sulfonic acid (impurity C) which are genotoxic impurities in fashudil hydrochloride.

    Methods:

    The LC-MS/MS method was achieved by a Waters Symmetry C18(100 mm×3 mm, 3.5 μm) column utilizing a mobile phase of 0.1% formic acid aqueous solution-acetonitrile with gradient elution at a flow rate of 0.5 mL·min-1. The column temperature was set at 30 ℃, the injection volume was 10 μL. The electrospray was operated with the source ESI under positive ionization scanning mode, and data were collected and analyzed.

    Results:

    Standard curves of impurity A and impurity C have a good linear relationship in the linear range. The limits of detection were 0.2 and 0.02 ng·mL-1, respectively, and the average recovery range was 93.0%~98.0%, RSD<4.67%(n=9). The RSDs of precision, accuracy, stability and durability tests were all less than 10.0%. Impurities A and C in the 3 batches of fashudil hydrochloride were not detected.

    Conclusion:

    The established method was fast, accurate and reproducible, which could be used for the control of genotoxic impurities A and C in fashudil hydrochloride.

  • Chao LI, Yi-fang PEI, Ting LI, Tian ZHANG, Ling TAN
    Chinese Journal of New Drugs. 2021, 30(13): 1242-1248.
    Objective:

    Ranibizumab prevents the formation of new blood vessels and reduces blood vessel permeability via inhibiting vascular endothelia growth factor (VEGF). In clinical, it is mainly used to treat wet age-related macular degeneration (wAMD). In this study, the safety, effectiveness and economics of ranibizumab in the treatment of wAMD were evaluated in order to provide an evidence-based basis for clinical rational use.

    Methods:

    Databases were systematically searched, including Pubmed, Ovid, the Cochrane Library, CNKI, Wanfang and CMB, according to the inclusion and exclusion criteria. The literatures were screened, the data were extracted, and then qualitative analysis on the results was conducted by 2 researchers separately.

    Results:

    17 Meta-analyses and 27 pharmacoeconomic studies were included. The results showed that the clinical effectiveness of ranibizumab in the treatment of wAMD was similar to bevacizumab, conbercept and aflibercept. However, compared with the combination of photodynamic therapy (PDT), the single use of ranibizumab had more benefit in improving patients' vision, especially on BCVA. In terms of safety, ranibizumab is safer than bevacizumab. Ranibizumab appeared significantly more cost-effective than the usual treatments, pegaptanib and PDT, while it is not cost-effective compared with bevacizumab, aflibercept and conbercept.

    Conclusion:

    In the treatment of wAMD, ranibizumab has no significant advantage over other clinically available drugs in effectiveness, but higher safety than bevacizumab, and lower economical than bevacizumab, aflibercept and conbercept.

  • Wen YAO, Jian-zhou YAN, Rong SHAO
    Chinese Journal of New Drugs. 2021, 30(12): 1057-1062.

    The aim of the article was to provide references for improving the evaluation criteria of medical insurance negotiation admittance for innovative drugs by studying the design and framework of the evaluation criteria of medical insurance negotiation admittance for innovative drugs in typical countries, combined with the current situation in China. The relevant evaluation criteria of New Zealand, Germany, and France were reviewed and summarized, and their characteristics was analyzed and compared with that of China. The reference significance to our country was discussed. Typical countries are more mature in terms of the evaluation system of medical insurance negotiation admittance for innovative drugs, and the diversity of evaluation content, scientificity of evaluation criteria and transparency of negotiation criteria could provide references to our country. It is suggested that China should improve the setting of evaluation criteria from the following aspects: requirement to submit authentic and available cost analysis data for the use of pharmacoeconomic evaluation research, clarifying the evaluation criteria for the varieties of medical insurance negotiation admittance, and establishing good risk control mechanism.

  • Hui LI, Fa-you ZHOU, Xiao-li YANG, Shi-hong MA, Jin-fang SHENG
    Chinese Journal of New Drugs. 2021, 30(12): 1063-1067.

    By analyzing the main content of the antimicrobial efficacy test of the Chinese Pharmacopoeia 2020 edition, the inherent requirements of the method were explored. The requirements of the Chinese Pharmacopoeia 2020 edition on the test bacteria, preparation of the bacterial solution, inoculation of test products, determination of viable bacteria, and determination of results have been further supplemented, and the standards have become more scientific and reasonable. The antimicrobial efficacy test of Chinese Pharmacopoeia 2020 edition has been further improved to become a more comprehensive testing method, which was beneficial to the screening and evaluation of antimicrobial agents in the research and development phase of new drugs.

  • Wei WANG, Jian-qiang XUE
    Chinese Journal of New Drugs. 2021, 30(12): 1068-1072.

    The database of INCOPAT platform was used to search patent applications of histone deacetylases (HDACs), and the data was analyzed, including its development trends, global patent applicants, PCT applications, the top 10 applicants, domestic applicants and their technical fields etc., aiming at providing references on new drug development and patent layout for domestic pharmaceutical enterprises, research and development institutions.

  • Jing-qi TANG, Xiao ZHANG
    Chinese Journal of New Drugs. 2021, 30(12): 1073-1078.

    In order to solve the impact of the entry of high-value drugs on the sustainability of medical insurance, some countries have actively explored the role of managed entry in improving the availability of high-value drugs and reducing the risk of medical insurance funds, and achieved certain success. This research systematically sorted out the relevant policies of Australia's managed entry scheme for high-value drugs, including drug selection, agreement formulation, implementation management, data collection, and post-market reviews, and compared and analyzed Australia's managed entry scheme for high-value drugs and our country's negotiation access policy, thus to provide enlightenment and reference for our country to further improve the medical insurance access policy of high-value drugs.