Application of poly mannuronic acid propyl ester sulfate in preparing anti- H1N1 influenza A virus medication

A technology of propyl uronic acid and influenza virus, which can be used in antiviral agents, pharmaceutical formulations, medical preparations containing active ingredients, etc., and can solve problems such as drug resistance, strong toxic side effects, etc.

Inactive Publication Date: 2012-10-24
OCEAN UNIV OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Aiming at the disadvantages that the drugs for treating influenza A virus in the prior art are easy to produce drug resistance and have strong toxic and side effects, the invention provides the use of polymannuronate propyl sulfate in the preparation of anti-Influenza A (H1N1) virus drugs. application

Method used

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  • Application of poly mannuronic acid propyl ester sulfate in preparing anti- H1N1 influenza A virus medication
  • Application of poly mannuronic acid propyl ester sulfate in preparing anti- H1N1 influenza A virus medication
  • Application of poly mannuronic acid propyl ester sulfate in preparing anti- H1N1 influenza A virus medication

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Experimental program
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Effect test

Embodiment 1

[0025] Embodiment 1, the physicochemical property analysis of polymannuronate propyl ester sulfate

[0026] The present invention prepares and separates polymannuronic acid from seaweed polysaccharide alginate by acid degradation method, and then obtains polymannuronic acid propyl ester sulfate (in patent ZL88109698. The preparation method of polymannuronate propyl sulfate PMS is described).

[0027] The main structural general formula of described polymannuronate propyl sulfate is as follows:

[0028]

[0029] Where R=Na or CH 2 CH(OH)CH 3 , R'=H or SO 3 Na, at least one R'=SO in each sugar ring 3 Na, n≤50, more than 85% of the molecular skeleton is β-1,4-D-mannuronic acid, and the rest is α-1,4-L-guluronic acid, of which 40-60% of carboxyl groups are Esterification of propanol, the part C in the sugar residue 2 and C 3 The hydroxyl group on the position is replaced by a sulfate group, and the content of organic sulfur is 9-13%. The weight-average molecular weight o...

Embodiment 2

[0036] Embodiment 2, the effect of polymannuronic acid propyl ester sulfate PMS anti-influenza A H1N1 influenza virus proliferation in vitro

[0037] 1) Evaluation of the anti-infection effect of PMS at the cellular level against influenza A (H1N1) virus

[0038] Infection of dog kidney epithelial cells (MDCK) with influenza A virus mouse-adapted strain H1N1 (A / PR / 8 / 34, provided by Wuhan Institute of Virology, Chinese Academy of Sciences) was used to establish a cell model, and this cell model was combined with cytopathic (CPE) inhibition test The inhibitory activity and cytotoxicity of polymannuronate propyl sulfate PMS on IAV were detected by colorimetric method with thiazole basket (MTT), and the half inhibitory concentration IC was calculated 50 and the half cytotoxic concentration CC 50 . Ribavirin was selected as the positive control drug.

[0039] The experimental results are shown in Table 2 and image 3 shown. image 3 Among them, at the concentration of 12.5uM, ...

Embodiment 3

[0046] Embodiment 3, PMS anti-infection effect of influenza A (H1N1) virus in vivo

[0047] 1) Effects of PMS on lung lesions and body weight of mice infected with influenza A (H1N1) virus

[0048] SPF BALB / C mice were infected with nasal drops of mouse lung-adapted strain H1N1 (A / PR / 8 / 34) to establish an animal model, and this mouse model was used to test the effect of polymannuronate propyl sulfate PMS in vivo Effects against IAV infection.

[0049] Divide 80 female BALB / C mice with SPF grade of 14-16g into virus control group (model group), normal control group, positive drug ribavirin group, positive drug oseltamivir group according to body weight, PMS injection and PMS gavage group, 10 rats in each group. Except the normal group, all other groups were treated with 10LD under light ether anesthesia. 50 Infect the nose with IAV virus liquid drops, 40 μL per mouse. Ribavirin group and PMS injection group started intraperitoneal injection 1 day before virus infection, ose...

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Abstract

The invention provides applications of poly mannuronic acid propyl ester sulfate (PMS) in preparing anti- H1N1 influenza A virus medication. Experiments of the invention prove that PMS not only has great inhibition effect on the neuraminidase of the influenza A virus, but also has relatively good protection effect on canine kidney epithelial cells infected with the H1N1 influenza A virus, and can reduce the replication of the H1N1 virus with an effect that equal to the positive control medication ribavirin. Additionally, the PMS can effectively reduce the death rate of mice infected with the H1N1 influenza A virus and the survival time of the mice are prolonged. The poly mannuronic acid propyl ester sulfate provided by the invention has significant activity of inhibiting the neuraminidase of the H1N1 influenza A virus, and is proved to have good anti- H1N1 influenza A virus activity both in vivo and in vitro experiments, which shows the wide application prospect of the poly mannuronic acid propyl ester sulfate in preparing anti-H1N1 influenza A virus medication.

Description

technical field [0001] The invention belongs to the field of marine medicines, and in particular relates to the application of polymannuronate propyl sulfate in the preparation of anti-type A (H1N1) influenza virus medicines. Background technique [0002] Influenza A is an acute respiratory infectious disease caused by Influenza A Virus (IAV), which is highly contagious and highly pathogenic, and seriously endangers human health. Influenza A virus (IAV) belongs to Orthomyxoviridae and has an enveloped negative-strand RNA virus. According to the different antigenic properties of the hemagglutinin protein (HA) and neuraminidase protein (NA) on its surface Can be divided into several subtypes, such as H1N1, H3N2 and so on. IAV has caused at least three large-scale influenza outbreaks in the last century, the worst of which was the Spanish flu outbreak in 1918-1919, which killed more than 40 million people. According to the statistics of the World Health Organization, about 60...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/715A61K31/702A61K31/7016A61P31/16
Inventor 王伟李春霞管华诗于广利王世欣
Owner OCEAN UNIV OF CHINA
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