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Application of oligomeric mannuronic acid to preparation of medicine for resisting influenza A virus subtype H1N1

A mannuronic acid, influenza virus technology, applied in antiviral agents, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problems of large molecular weight, poor solubility and absorption, limited application, etc. Activity, small molecular weight, good solubility and stability of influenza A H1N1 virus

Inactive Publication Date: 2012-06-13
OCEAN UNIV OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, polysaccharide drugs have large molecular weight, poor solubility and absorption, resulting in low bioavailability, which limits their clinical application.
Scholars at home and abroad have reported some patents (ZL01107952.5, CN1414002A, CN1562050A, CN101037456A) on the preparation and application of fucoidan oligosaccharides, but there is no research on oligomannuronic acid in anti-influenza A (H1N1) virus and application coverage

Method used

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  • Application of oligomeric mannuronic acid to preparation of medicine for resisting influenza A virus subtype H1N1
  • Application of oligomeric mannuronic acid to preparation of medicine for resisting influenza A virus subtype H1N1
  • Application of oligomeric mannuronic acid to preparation of medicine for resisting influenza A virus subtype H1N1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Embodiment 1, oligomannuronic acid OM in vitro anti-H1N1 influenza virus proliferation effect

[0022] Infected 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) to establish a cell model, and combined this cell model with cytopathic (CPE) inhibition test The inhibitory activity and cytotoxicity of oligomannuronic acid OM on IAV were detected by colorimetric method with thiazole basket (MTT), and the half inhibitory concentration IC50 and half cytotoxic concentration CC50 were calculated. Ribavirin was selected as the positive control drug.

[0023] The experimental results are shown in Table 1. The inhibitory activity of oligomannuronic acid OM on IAV is very significant (IC 50 =38.3μM), and less cytotoxic (CC 50 =420μM), therapeutic index SI (CC 50 / IC 50 ) reached 11.0. Compared with the broad-spectrum antiviral drug ribavirin, the drug concentrati...

Embodiment 2

[0026] Embodiment 2, oligomannuronic acid OM anti-infection effect of influenza A (H1N1) virus in vivo

[0027] 1), the impact of OM on the lung pathology and body weight of mice infected with influenza A H1N1 virus

[0028] SPF grade Kunming mice were established by intranasally infecting SPF-grade Kunming mice with mouse lung-adapted strain H1N1 (A / PR / 8 / 34), and the effect of oligomannuronic acid OM on IAV infection in vivo was tested using this mouse model .

[0029] 40 female Kunming mice of SPF grade of 14-16 g were divided into virus control group, normal control group, positive drug ribavirin group and oligomannuronic acid group according to body weight, with 10 mice 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. The ribavirin group and the oligosaccharide drug group started intraperitoneal injection administration 1 day before virus infecti...

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Abstract

The invention provides application of oligomeric mannuronic acid to preparation of a medicine for resisting influenza A virus subtype H1N1. Through experiment, the oligomeric mannuronic acid (OM) has a good function of protecting madin-darby canine kidney cells which are infected by influenza A virus subtype H1N1 in vitro, can effectively reduce virus reproduction, and has an effect equal to thatof a positive control medicine ribavirin. Moreover, OM can also reduce the death of mice which is caused by infection of influenza A virus subtype H1N1 obviously, and prolong the survival time. The oligomeric mannuronic acid (OM) has the advantages of high water solubility and stability, and safety and low toxicity and the like; and in an in vivo-in vitro experiment, the OM can resist influenza Avirus subtype H1N1 well, and the oligomeric mannuronic acid can be expected to be developed to the medicine for resisting influenza A virus.

Description

technical field [0001] The invention belongs to the field of marine drugs and relates to the application of oligomannuronic acid in the preparation of drugs against influenza A (H1N1) virus. Background technique [0002] Influenza A Virus (IAV) belongs to Orthomyxoviridae and has enveloped negative-strand RNA virus, according to the hemagglutinin protein (HA) and neuraminidase protein (NA) on its surface Different structural and genetic characteristics can be divided into several subtypes, such as H1N1, H5N1 and H3N2. 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. Since April 2009, the H1N1 subtype influenza A virus originating in Mexico has caused worldwide influenza outbreaks, posing a huge threat to human health. According to the statistics of the World Health Organization, about 600 million people around the world are infected with...

Claims

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Application Information

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IPC IPC(8): A61K31/7016A61K31/702A61K31/715A61P31/16
Inventor 王伟于广利郝翠管华诗
Owner OCEAN UNIV OF CHINA
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