Therapeutic agent for inflammatory diseases, containing adenosine n1-oxide as an effective ingredient

a technology of adenosine n1oxide and a therapeutic agent, which is applied in the direction of antibacterial agents, immunological disorders, metabolism disorders, etc., can solve the problems of not yet being explored a chemotherapeutic agent that exerts satisfactory, side effects, and relatively strong systemic side effects, and achieves effective prevention or treatment of inflammatory diseases, enhances the production of il-10, and effectively inhibits the production of inflammatory cytokines

Inactive Publication Date: 2013-06-27
HAYASHIBARA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013]The therapeutic agent, containing adenosine N1-oxide or a derivative thereof as an effective ingredient, effectively prevents or treats inflammatory diseases such as sepsis, rheumatoid arthritis, ARDS, hepatitis, and inflammatory bowel disease. I

Problems solved by technology

At present, there has not yet been explored a chemotherapeutic agent that exerts a satisfactory result for inflammatory diseases such as sepsis and hepatitis, and there have been only applied steroids, anti-inframmatories, platelet aggregation inhibitors, vasodilators, antibiotics, etc., as supportive measures to the above diseases.
WO03/007974) have been tried to apply for the treatment of such inflammat

Method used

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Examples

Experimental program
Comparison scheme
Effect test

experiment 1

Influence 1 of the Administration of Adenosine N1-Oxide on Bacterial Shock

[0037]The influence of the administration of adenosine N1-oxide on sepsis was examined by using lipopolysaccharide (LPS)-induced endotoxin shock mice (see, for example, “Circulation”, Vol. 111, pp. 97-105, 2005), which have been used widely as a model of bacterial shock accompanied by human sepsis. Fifteen BALB / c mice (9-week-old, female, commercialized by Charles River Laboratories Japan Inc., Tokyo, Japan) were randomly divided into three groups, five heads each (Experiment groups 1 to 3), and intraperitoneally administered with 15 mg / kg body weight of an LPS specimen derived from Escherichia coli (055:B5), commercialized by Sigma-Aldrich Corporation, St. Louis, Mo. USA, which had been dissolved in phosphate buffered saline (PBS) (Experiment groups 1 to 3). Among these groups, five heads of one group were intravenously administered with 15 mg / kg body weight of adenosine N1-oxide (prepared by Hayashibara Bioc...

experiment 2

Influence 1 of Adenosine N1-Oxide on the Production of TNF-α From Mouse Intraperitoneal Macrophage

[0040]The confirmation of the fact that the administration of adenosine N1-oxide inhibits bacterial shock in mice administered with LPS in Experiment 1 led to examine the inhibitory mechanism of bacterial shock induced by adenosine N1-oxide in this experiment. It has been known that TNF-α induced by bacterial LPS is an effector molecule in bacterial shock in human sepsis (see, for example, “Journal of Immunology”, Vol. 187, No. 3-5, pp. 346-356, 1993). The influence of adenosine N1-oxide on the production of TNF-α was examined by using mouse intraperitoneal macrophages known as an in vitro model of bacterial shock in human sepsis (see, for example, “The Journal of Immunology”, Vol. 164, No. 9, pp. 1013-1019, 2000). It is known that mouse intraperitoneal macrophages respond to LPS to produce TNF-α whose production is more enhanced by the coexistence of IFN-γ. In bacterial shock, not only...

experiment 3

Influence 2 of Adenosine N1-Oxide on the Production of TNF-α And IL-6 from Mouse Intraperitoneal Macrophages

[0044]Macrophages have been known to use a receptor called “Toll Like Receptor” (may be called “TLR”, hereinafter) to recognize adventive pathogenic microorganisms, while LPS has been known to be recognized by a receptor called TLR4. It was confirmed that, in Experiment 2, the production of TNF-α from mouse intraperitoneal macrophages, induced by the stimulation of LPS derived from a gram negative microorganism and identified as a causative substance of bacterial shock, is effectively inhibited by adenosine N1-oxide. In this experiment, it was examined the influence of adenosine N1-oxide on the production of TNF-α from mouse intraperitoneal macrophages induced by the stimulation of a component derived from a microorganism, which has been recognized as a causative of inflammatory diseases and which is recognized by a receptor other than TLR4 and is derived from the one excludin...

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Abstract

The present invention has an object to provide an effective and safe therapeutic agent for inflammatory diseases such as sepsis, hepatitis, and inflammatory bowel disease, and solves the above object by providing a therapeutic agent for inflammatory diseases containing adenosine N1-oxide or a derivative thereof as an effective ingredient.

Description

TECHNICAL FIELD[0001]The present invention relates to an agent for treating inflammatory diseases such as sepsis and hepatitis, more particularly, to a therapeutic agent for inflammatory diseases, containing adenosine N1-oxide as an effective ingredient.BACKGROUND ART[0002]At present, there has not yet been explored a chemotherapeutic agent that exerts a satisfactory result for inflammatory diseases such as sepsis and hepatitis, and there have been only applied steroids, anti-inframmatories, platelet aggregation inhibitors, vasodilators, antibiotics, etc., as supportive measures to the above diseases. Since these inflammatory diseases exhibit serious symptoms in many cases, there has been desired an exploitation of therapeutically effective agents with no or lesser side-effects but with safeness.[0003]It is known that many cytokines are involved in various inflammatory diseases in living bodies. Examples of such inflammatory cytokines include a number of tumor necrosis factor (TNF-α...

Claims

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Application Information

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IPC IPC(8): A61K31/7076A61K45/06
CPCA61K31/7076C07H19/167A61K31/708A61K45/06C07H19/067A61K8/602A61K31/7052A61K31/7056A61K31/706A61K31/7064A61K2800/10A61P1/00A61P1/02A61P1/04A61P1/16A61P1/18A61P3/10A61P13/12A61P17/00A61P29/00A61P31/04A61P31/10A61P37/00A61Q17/04A61Q19/00A61Q19/007A61Q19/08
Inventor KOHNO, KEIZOOHASHI, EMIKOKUSANO, HAJIMEFUKUDA, SHIGEHARUISHIHARA, TATSUYA
Owner HAYASHIBARA CO LTD
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