Application of andrographolide C15 substituted series derivatives to preparation of medicine for resisting hepatitis B

A technology of andrographolide and preparation of drugs, which is applied in the direction of drug combination, digestive system, antiviral agents, etc., can solve the problems of easy drug resistance, adverse reactions, rebound, etc., to expand the range of options and clarify the anti-HBV active effect

Active Publication Date: 2012-01-04
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In clinical application, there are problems such as rebound after drug withdrawal, adverse reactions and easy drug resistance

Method used

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  • Application of andrographolide C15 substituted series derivatives to preparation of medicine for resisting hepatitis B
  • Application of andrographolide C15 substituted series derivatives to preparation of medicine for resisting hepatitis B
  • Application of andrographolide C15 substituted series derivatives to preparation of medicine for resisting hepatitis B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Anti-HBV Activity Experiment of Andrographolide Derivatives in Vitro

[0036] 1. Cell culture and drug treatment

[0037] Human liver cancer HepG2.2.15 cells transfected with human hepatitis B virus gene are used to detect the effect of the drug of the present invention on the secretion of HBV surface antigen (HBsAg) in the culture supernatant of HepG2.2.15 cells. The HepG 2.2.15 cell suspension was seeded in a 48-well plate with a cell number of 1.25×10 4 To each well, add 0.5 mL of RPMI1640 culture medium, which contains 10% fetal bovine serum, 380 μg / mL G418, 100 μg / mL streptomycin, 100 IU / mL penicillin, and 5% CO 2 Place them in a carbon dioxide incubator at 37 °C for culture, and change the drug-containing culture medium every 24 h, and set 5 gradients of drug concentration. Lamivudine (3TC) was used as positive drug control. The culture medium was changed once at 3d and 6d of culture respectively, and the supernatant in the culture well was taken out ...

Embodiment 2

[0046] Example 2 In vivo anti-DHBV activity experiment of andrographolide derivatives

[0047] 1. Experimental animals and materials: Cherry Valley duck, male, purchased from a duck factory; DHBV positive serum was collected and preserved by our laboratory.

[0048] 2. Instruments, drugs and their preparation: the model LightCycler? 1.5 fluorescent quantitative PCR system produced by Swiss Roche Company; the Milli-Q-B.S ultrapure water instrument produced by Millipore Co., Ltd. of the United States; centrifuge. Compounds A-G of the present invention were synthesized by the applicant; lamivudine is commercially available. The above-mentioned experimental drugs were formulated into 0.5% CMC-Na solution, and dissolved with Tween-80 (final concentration 0.1%). SYBR Green I is a product of Bao Biological Engineering (Dalian) Co., Ltd. The upstream and downstream primers were synthesized by Sangon Bioengineering (Shanghai) Co., Ltd.

[0049] 3. Experimental method:

[0050] Abo...

Embodiment 3

[0055] Example 3 Limit Toxicity Test of Compounds A and B

[0056] Animals: clean-grade Kunming mice, weighing 20±2 g, half male and half male, provided by the Experimental Animal Center of Henan Province. Certificate number: 0009898.

[0057] Drugs: Compounds A and B synthesized by the applicant.

[0058] Experimental method: Animals were randomly divided into groups, and after fasting for 12 hours (drinking water was not restricted), compound A and B at a dose of 5.00 g / kg were administered orally once. Observe and record the state of the animals, whether there is any poisoning performance. The results are shown in Table 1.

[0059] Experimental results: The mice did not show obvious signs of poisoning, and did not die, indicating that the acute toxicity of this type of compound is minimal. As preparation of anti-HBV medicine, it has good practical and development value.

[0060]

[0061] Table 1 Limited Toxicity Test

[0062] compound Dose (g / kg) n...

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Abstract

The invention belongs to the technical field of medicinal chemistry, and discloses application of andrographolide C15 substituted series derivatives to the preparation of a medicine for resisting hepatitis B. HepG2.2.15 cells are used for detecting the secretion amount of hepatitis B surface antigen (HBsAg) in culture solution supernatant, a large number of andrographolide derivative compounds are screened, and compounds which have high hepatitis B virus (HBV) resistance are optimally selected and have a structure shown in a general formula 1; and the compounds have high HBV-resistant activity, high efficiency and low toxicity and are taken as active ingredients to be used for preparing a medicine for resisting viral hepatitis B, and a new medicine is provided for treating hepatitis, so that the selectable range of clinical medicines is expanded.

Description

technical field [0001] The invention relates to the medicinal use of andrographolide derivatives, in particular to the application of andrographolide C15-position substituted series derivatives in the preparation of anti-hepatitis B drugs, and belongs to the technical field of medicinal chemistry. Background technique [0002] Andrographolide (AD) is a plant of Andrographis paniculata [ Andrographis paniculata (Burm. f) Nees], which is one of the main active ingredients of the traditional Chinese medicine Andrographis paniculata, is mainly used in the treatment of upper respiratory tract infection, bacillary dysentery and other diseases in clinical practice. In recent years, studies have found that andrographolide also has anti-tumor, liver-protecting and gallbladder-protecting, anti-viral effects. There have been many reports on the antiviral research of Andrographis paniculata and its extracts. Andrographis paniculata extract can effectively treat respiratory tract infec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/365A61P31/20A61P1/16
CPCC07D307/33A61K31/365A61P1/16A61P31/20
Inventor 戴桂馥徐海伟蒋志雯刘宏民王亚楠李伟义巫凤娟朱丽平
Owner ZHENGZHOU UNIV
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