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Prevention of nsaid enteropathy with microbiota-derived tryptophan-metabolite

a technology of microbiota and enteropathy, applied in immunology, instruments, antibody medical ingredients, etc., can solve the problems of high morbidity and mortality, enteropathy is associated, etc., and achieve the effects of reducing mucosal pathology scores, fecal calprotectin concentrations, and neutrophil infiltration

Inactive Publication Date: 2019-03-21
TRUSTEES OF TUFTS COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method for treating dysbiosis, a condition that can cause enteropathy, by administering a subject a drug that causes a reduction in a specific component of the microbiota (gram-positive) or an increase in a different component (gram-negative). The method involves co-administering a specific compound (TDMM) with the drug or delivering it through various routes such as intra-peritoneal injection, intravenous infusion, or orally. The technical effect of this method is to prevent or treat dysbiosis and enteropathy.

Problems solved by technology

Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality.

Method used

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  • Prevention of nsaid enteropathy with microbiota-derived tryptophan-metabolite
  • Prevention of nsaid enteropathy with microbiota-derived tryptophan-metabolite
  • Prevention of nsaid enteropathy with microbiota-derived tryptophan-metabolite

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Embodiment Construction

[0023]The pathophysiology of NSAID enteropathy is complex and incompletely understood. It appears to involve deleterious effects of NSAIDs on the intestinal mucosa including enterocyte cell death, increased mucosal permeability, and interaction of the damaged mucosa with luminal contents including bacteria (GI microbiota) and bacterial products or components such as lipopolysaccharide (LPS). The GI microbiota has been implicated as an important contributor to NSAID enteropathy. For example, administration of NSAIDs causes a dysbiosis characterized by a reduction of the predominately gram-positive phylum Firmicutes and a corresponding increase of gram-negative bacteria. Germ-free rats lacking intestinal microbiota do not develop NSAID enteropathy, whereas they develop NSAID-induced intestinal lesions when colonized with gram-negative bacteria. Concurrent administration of NSAIDs and antimicrobials targeting gram-negative bacteria reduces the severity of NSAID-induced gastrointestinal...

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Abstract

This disclosure relates to methods and compositions for addressing conditions of dysbiosis and / or inflammation, such as enteropathy, associated with administration of non-steroidal anti-inflammatory drug (NSAID). The disclosure includes methods comprising administering an effective amount of a tryptophan derived microbiota metabolite (TDMM) to a subject that has also been administered, or is expected to have administered, a NSAID.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims the benefit of Provisional Application No. 62 / 310,606, filed Mar. 18, 2016, Provisional Application No. 62 / 310,648, filed Mar. 18, 2016, Provisional Application No. 62 / 310,643, filed Mar. 18, 2016, and Provisional Application No. 62 / 310,630, filed Mar. 18, 2016, each of which is expressly incorporated herein by reference in its entirety.STATEMENT OF GOVERNMENT LICENSE RIGHTS[0002]This invention was made with Government support under GM106251 awarded by The National Institutes of Health, National Institute of General Medical Sciences; AI110642 awarded by The National Institutes of Health, National Institute of Allergy and Infectious Disease; A095788 awarded by The National Institutes of Health, National Institute of Allergy and Infectious Disease; and MCB-1120827, awarded by the National Science Foundation. The Government has certain rights in the invention.FIELD OF THE INVENTION[0003]This disclosure relates to met...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/405A61K45/06A61P1/00
CPCA61K31/405A61K45/06A61P1/00A61K31/475A61K31/404C12N2501/999A61P29/00A61K31/7004C12N5/0637A61K2035/122A61K2039/577C12N2502/1121A61P37/06C12N2501/2302C12N2501/51C12N2501/515C12N2501/15C12N2501/24C12N2501/2306C12N2501/2323C12N2501/2304C12N5/0636C12N2500/30C12N2500/36A61K2039/57G16B40/20G16B20/00G16B5/00A61K2239/38A61K39/4615A61K2239/31C12N5/064A61K39/4644A61K39/4622A61K39/4611C12N2501/2301C12N2501/2321C12N2501/2312C12N2502/1157
Inventor ALANIZ, ROBERT C.JAYARAMAN, ARULLEE, KYONGBUMWHITFIELD, CANAANCOHEN, NOAH
Owner TRUSTEES OF TUFTS COLLEGE
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