Compositions and methods for reducing hepatotoxicity associated with drug administration and treating non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and associated cirrhosis

a technology of hepatotoxicity and drug administration, which is applied in the direction of aerosol delivery, spray delivery, immunological disorders, etc., can solve the problems of hepatocyte death, reduce the usefulness of bioactive agents, and increase the effectiveness of such agents

Inactive Publication Date: 2009-09-24
YALE UNIV
View PDF10 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0022]The present method is applicable and adaptable to a large number of heptatoxicity-inducing bioactive agents which produce hepatotoxicity and limit their usefulness because of that hepatotoxicity. The present invention may be used to increase the effectiveness of such bioactive agents (for example by increasing an agent's therapeutic index and/or increasing the dose which may be administered to a patient). Pursuan

Problems solved by technology

The initial event in APAP induced hepatotoxicity is a toxic-metab

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Compositions and methods for reducing hepatotoxicity associated with drug administration and treating non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and associated cirrhosis
  • Compositions and methods for reducing hepatotoxicity associated with drug administration and treating non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and associated cirrhosis
  • Compositions and methods for reducing hepatotoxicity associated with drug administration and treating non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and associated cirrhosis

Examples

Experimental program
Comparison scheme
Effect test

examples

[0202]The following description of experiments conducted are presented to exemplify the present invention. They are by way of example only and are not to be taken the limit the invention in any way.

Materials and Methods

Animals.

[0203]C57BL / 6 mice were purchased from commercial sources. NALP3 − / −, IL-18 − / − ASC − / −, IPAF − / − and TLR9 − / − mice were backcrossed nine generations onto the C57BL / 6 background. Caspase 1 − / − mice were backcrossed 5-6 generations onto the C57BL / 6 background. These mice have been described previously (39, 40). IL-1β was neutralized in by using the anti-IL-1β antibody from clone B122 (a gift of R. Schreiber, Washington University) at a dose of 0.2 mg / mouse iv twice a day for a total of 48 hours after giving APAP. Control mice received Armenian hamster isotype control antibody. For survival experiments animals were euthanized when they became moribund using criteria of lack of response to stimuli or lack of righting reflex. Animal protocols were approved by the...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Fractionaaaaaaaaaa
Therapeuticaaaaaaaaaa
Antimicrobial propertiesaaaaaaaaaa
Login to view more

Abstract

The present invention relates to the discovery that acetylsalicylic acid (ASA or aspirin), salicylic acid (SA) and related salicylate esters and their pharmaceutically acceptable salts, when coadministered in effective amounts with a drug or other bioactive agent which typically (in the absence of the salicylate compound) produces significant hepatotoxicity as a secondary indication, will substantially reduce or even eliminate such hepatotoxicity. Favorable therapeutic intervention results from the use of the present invention having the effect of reducing hepatotoxicity associated with the administration of certain drugs and other bioactive agents and in certain instances of allowing the administration of higher doses of a compound which, without the coadministration, would produce hepatotoxicity which limits or even negates the therapeutic value of the compound. The invention also relates to methods of reducing the likelihood of a patient at risk for non-alcoholic fatty liver diseases (NAFLD), including non-alcoholic steatohepatitis (NASH), or treating NAFLD or NASH including primary NASH, NASH secondary to liver transplantation (NASH post-liver transplantation) or cirrhosis represent alternative aspects of the present invention.

Description

RELATED APPLICATIONS AND GOVERNMENT SUPPORT[0001]This application is a continuation-in-part application of international application PCT / US08 / 11945, entitled “Compositions and Methods for Reducing Haptotoxicity Associated with Drug Administration”, filed Oct. 20, 2008, which claims the benefit of priority of U.S. provisional application Ser. No. 60 / 999,413, filed Oct. 18, 2007, entitled “Protection From Acute and Chronic Liver Injury by Therapeutic Doses of Aspirin”, the entire contents of each of said patent applications being incorporated by reference herein.[0002]This invention was supported by grants from the National Institutes of Health, grant numbers NIH K08 AI065517, NIH R01DK076674-01A2 and NIH T32 DK7356. The government retains rights in this invention.FIELD OF THE INVENTION[0003]The present invention relates to the discovery that acetylsalicylic acid (ASA or aspirin), salicylic acid (SA) and related salicylate esters and their pharmaceutically acceptable salts, when coadm...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K31/60A01N1/02
CPCA61K9/0014A61K9/0019A61K9/0031A61K9/0046A61K9/0048A61K9/0073A61K9/02A61K45/06A61K31/60A61K31/198A61K2300/00A61K31/616A61P1/16A61P37/06A61K36/38
Inventor MEHAL, WAJAHATAVLIN, IMAEDA
Owner YALE UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap