Application of vitamin D analogue for treating or preventing viral hepatitis
A technology for viral hepatitis and derivatives, applied in antiviral agents, drug combinations, organic active ingredients, etc., to achieve excellent clinical safety, excellent pharmacokinetic properties, and good druggability
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Embodiment 1
[0109] Example 1 - Application of HepG2-NTCP cells to evaluate the in vitro anti-HBV activity of paricalcitol (HD009, compound 9), alfacalcitol (HD125, compound 18) and calcifediol (HD135, compound 3)
[0110] Compound preparation method is as follows:
[0111] Take the preparation of 20mM concentration as an example, the volume of solvent DMSO (μl) = sample mass (mg) × purity ÷ molecular weight ÷ 20 × 10 6
[0112] Control compounds include ETV (Entecavir) (batch number: P1214012; 99.0% purity), purchased from Shanghai Titan Technology Co., Ltd.; HD131 (vitamin D2), HD132 (vitamin D3), HD134 (docalcitol), purchased from Shanghai Tao Su Biochemical Technology Co., Ltd. The concentration of the stock solutions of the above control compounds was 20 mM and stored at -20°C.
[0113] Table 1. Major Reagents and Cell Viruses
[0114]
[0115] Experimental program
[0116] Plating Cells and Compound Treatment
[0117] On day 0, HepG2-NTCP was plated into 48-well plates (7....
Embodiment 2-A
[0153] Embodiment 2-AAV HBV mouse model experiment
[0154]Administration was carried out according to the following table 7, and the content of HBV DNA, HBeAg and HBsAg in the cell culture supernatant was detected with reference to the same method as above, and the results are shown in Table 8:
[0155] Table 7
[0156] way of administration time blank 0, once a day 7 days HD125 2ug / kg, once a day 7 days
[0157] Table 8
[0158] HD125 Log HBV DNA Log HBsAg Log HBeAg 0day 6.56 3.41 2.66 7day 4.61 2.96 2.61 Variation -1.95 -0.45 -0.05
[0159] Animal experiment results also show that HD125 (alfacalcidol) can effectively reduce HBV DNA, HBsAg and HBeAg, showing good antiviral effect in vivo.
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