1.Mechanism of action, clinical research and development, and application prospect of hepatitis B virus core protein allosteric modulators
Hui LIU ; Fengmin LU ; Jutao GUO
Journal of Clinical Hepatology 2022;38(8):1726-1732
Hepatitis B virus (HBV) infection is the main pathogenic factor for chronic hepatitis, and if it is not treated timely and effectively, it may have the risk of developing into end-stage liver diseases such as liver cirrhosis and hepatocellular carcinoma. Neither of the two types of antiviral drugs currently used in clinical practice can completely inhibit viral replication or eliminate viral transcriptional template, which means that covalently closed circular DNA (cccDNA) exists in infected liver cells for a long time, and thus patients with chronic hepatitis B require long-term or even lifelong medication. Therefore, it is of great importance to develop novel anti-HBV drugs. Core protein allosteric modulators (CpAM) are a type of novel anti-HBV drugs and can interfere with HBV nucleocapsid assembly and inhibit the depolymerization of mature nucleocapsid, the formation of cccDNA, and the biogenesis and secretion of HBeAg. CpAM have a great potential in clinical application since they act on various links of viral replication. This article reviews the function of CpAM target protein-core protein, the classification, action targets, and anti-HBV mechanism of CpAM, and the current research status, further development, and application prospect of CpAM.
2.Method Improvement for Content Determination of Astragaloside Ⅳ in Xiangju Granules and Its Consistency with the Com- ponents of Original Formulation
Chenxi SUN ; Ding GE ; Sumei WANG ; Kang GUO ; Jutao WANG
China Pharmacy 2019;30(14):1914-1919
OBJECTIVE: To improve the method for the content determination of astragaloside Ⅳ in Xiangju granules, and to evaluate the consistency of relevant preparations with the components of original formulation, so as to provide evidence for the modern preparation of TCM compound. METHODS: HPLC-ELSD method was established for the content determination of astragaloside Ⅳ in Xiangju granules, and compared with original standard TLC scanning. Using critrinin, ferulic acid, calycosin glucoside, liquiritin, glycyrrhizic acid, rosmarinic acid, buddleoside and magnoline as control, HPLC method was used to determine the release components of self-made Xiangju granules, Xiangju capsules, Xiangju tablets in water. Fingerprint characteristics chromatogram of different Xiangju preparations and original formulation extract were compared by using Similarity Evaluation System for Chromatographic Fingerprint of TCM (2012 version). At the same time, HPLC-ELSD method was used to determine and compare the release rate of astragaloside Ⅳ from different Xiangju preparations and original formulation extract in water. RESULTS: Established HPLC-ELSD method was specific. The linear range of astragaloside Ⅳ was 0.13-2.10 mg/mL. RSDs of precision, repeatability and stability tests were all lower than 3% (n=6), and average recovery was 97.66% (RSD=1.01%,n=6). Average content of astragaloside Ⅳ by this method was 0.398 mg/g (RSD=1.01%, n=3), which had better reproducibility than TLC scanning. The comparative results of characteristic fingerprints showed that the similarity among Xiangju granules, Xiangju capsules, Xiangju tablets and the original formulation dry extract powder was more than 0.850. Average release rates of astragaloside Ⅳ in Xiangju granules, Xiangju capsules, Xiangju tablets and the original formulation extract were 0.392, 0.358, 0.349, 0.389 mg, respectively. Compared with original formulation extract, there was no statistical significance in release rate of astragaloside Ⅳ in Xiangju granules (P>0.05), while there was statistical significance in Xiangju capsules and Xiangju tablets (P<0.01). CONCLU- SIONS: Established HPLC-ELSD method is accurate and feasible, and is suitable for the content determination of astragaloside Ⅳ in Xiangju granules. The main components of Xiangju granules are consistent with original formulation.