Application of ring E bromine substituted silybin in preparing medicaments for treating viral hepatitis B

A technology of silibinin and bromine substitution, applied in the field of medicine, can solve problems such as new uses not being effectively developed, and achieve the effects of being beneficial to large-scale production, clear industrialization prospects, and large-scale production of energy saving and emission reduction.

Inactive Publication Date: 2012-05-23
DALI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] Although the flavonoid lignans represented by silibinin have the above-mentioned antioxidant effects, there are relatively few literatures on their antiviral treatment. The flavonoid lignans treat DNA virus infection especially Its new application for anti-hepatitis B virus (including inhibition of hepatitis B surface antigen HBsAg or HBeAg, inhibition of HBV DNA replication) has not been effectively developed, so the active compound in the field of anti-hepatitis B virus is sought from flavonolignans, also known as flavonoids Structural modification of lipids to have anti-DNA virus activity is a new field

Method used

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  • Application of ring E bromine substituted silybin in preparing medicaments for treating viral hepatitis B
  • Application of ring E bromine substituted silybin in preparing medicaments for treating viral hepatitis B
  • Application of ring E bromine substituted silybin in preparing medicaments for treating viral hepatitis B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: Formula (1) compound (±)-2-[2,3-dihydro-3-(3-bromo-4-hydroxyl-5-methoxyphenyl)-2-hydroxymethyl-1,4-benzene Preparation of dioxane-6-]-2,3-dihydro-3,5,7-trihydroxy-4H-1-benzopyran-4-one

[0031] 1.1 Instruments and reagents:

[0032] The ultraviolet spectrum was measured with a Shimadzu UV-240 ultraviolet spectrophotometer; the hydrogen nuclear magnetic resonance spectrum 1 H-NMR is measured by INOVA type superconducting nuclear magnetic resonance spectrometer (VARIAN INOVA-400MHz) (tetramethylsilyl ether TMS is the internal standard); (100-200, 200-300 and 300-400 mesh) and silica gel GF254 (10-40 mesh) for thin-layer chromatography are produced by Qingdao Ocean Chemical Factory; all reagents used are analytically pure, thin-layer preparative chromatography (PTLC ) uses the aluminum foil silica gel plate of Merck Company; Sephadex LH-20 used for column chromatography adopts the product of Amersham Pharmacia Biotech AB Company of Sweden; Reversed-phase sili...

Embodiment 2

[0040] Example 2: Inhibitory effect of compound (1) on hepatitis B surface antigen (HBsAg) secreted by HepG2.2.15 cells

[0041] 2.1 Cell culture:

[0042] HepG2.2.15 cells were cultured in DMEM medium containing 10% inactivated fetal bovine serum, 100U / ml penicillin and 100U / ml streptomycin, and 100 μg / ml G418 at 37°C, 5% CO. 2 , cultured in an incubator with 100% relative humidity.

[0043] 2.2 The inhibitory effect of the compound of formula (1) on the growth of HepG2.2.15 cells was determined by MTT method:

[0044] Take HepG2.2.15 cells in logarithmic growth phase and dilute the cells to 1 × 10 with culture medium 5 cells / ml, seeded in 96-well cell culture plates, 100 μl per well, at 37°C, 5% CO 2 , after 24 hours of incubation in an incubator with 100% relative humidity, compound (1) diluted with medium was added at concentrations of 1000 μg / ml, 200 μg / ml, 40 μg / ml and 8 μg / ml, 200 μg / ml per well. microliters, three replicate wells for each concentration, placed at...

Embodiment 3

[0053] Example 3: Inhibitory effect of compound (1) on hepatitis B e antigen (HBeAg) secreted by HepG2.2.15 cells

[0054] 3.1 Cell culture: the method is the same as that in Example 2.

[0055] 3.2 The inhibitory effect of the compound of formula (1) on the growth of HepG2.2.15 cells was determined by MTT method: the method was the same as that in Example 2.

[0056] 3.3 Determination of the inhibitory effect of compounds on hepatitis B e antigen (HBeAg): take HepG2.2.15 cells in logarithmic growth phase, and dilute the cells to 1×10 with culture medium 5 / ml, seeded in 96-well cell culture plates, 100 ml per well, at 37°C, 5% CO 2 , after culturing in a 100% relative humidity incubator for 24 hours, the samples diluted with culture medium were added at the concentrations of 100 μg / ml, 20 μg / ml and 4 μg / ml, 200 μl per well, and each concentration was set to three Duplicate wells, placed at 37°C, 5% CO 2 , culture in an incubator with 100% relative humidity, change the me...

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PUM

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Abstract

The invention relates to application of ring E bromine substituted silybin in preparing medicaments for treating viral hepatitis B, in particular to application of a compound of a formula (1) and a pharmaceutically acceptable salt thereof in preparing medicaments for clearing away hepatitis B surface antigens (HBsAg) and hepatitis e antigens (HBeAg) and suppressing the HBV (Hepatitis B Virus) DNA replication. The compound has definite activity on suppressing the HBsAg and the HBeAg, and in the presence of a concentration of 100 micrograms / milliliter, the intensities of the compound for clearing away the HBsAg and the HBeAg are respectively 38.2 percent and 39.1 percent which are respectively 2.4 times and 2.3 times of that of a positive control medicament (10,000 units / milliliter of alpha-interferon). Meanwhile, in the presence of the concentration, the suppression ratio of the compound on the HBV DNA is 36 percent which is close to that of the alpha-interferon. Accordingly, the flavone lignan or the pharmaceutically acceptable salt thereof are indicated to be capable of being used for preparing non-nucleoside medicaments for clearing away the HBsAg and the HBeAg, suppressing the HBV DNA replication and treating HBV infection diseases.

Description

technical field [0001] The present invention relates to the technical field of medicine, in particular, the present invention relates to a silybin ester substituted by E ring bromine or a pharmaceutically acceptable salt thereof, which is used to prepare and reduce hepatitis B virus surface antigen HBsAg and hepatitis B e antigen HBeAg, and inhibit HBV DNA Use of medicines for replicating or treating hepatitis B virus infection. This flavonoid lignan has definite activity of inhibiting HBsAg and HBeAg, and its intensity of removing HBsAg and HBeAg is respectively 38.2% and 39.1% under the concentration of 100 micrograms / ml. 2.4 times and 2.3 times; meanwhile, at this concentration, it shows a 36% inhibitory rate to HBV DNA, which is close to α-interferon. The above pharmacodynamic results show that the flavonoid lignan or its pharmaceutically acceptable salt can be expected to be used in the preparation of non-nucleoside drugs for eliminating HBsAg and HBeAg, inhibiting HBV D...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/357A61P31/20
Inventor 陈智陶巧凤马英王晓雨俞永平巫秀美赵昱戴志明
Owner DALI UNIV
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