Amino acid compositions for the treatment of liver disease

A technology of amino acids and compositions, applied in the field of amino acid compositions for the treatment of liver diseases, can solve problems such as no approval yet

Pending Publication Date: 2020-06-16
AXCELLA HEALTH INC
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, there are no approve

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
  • Amino acid compositions for the treatment of liver disease
  • Amino acid compositions for the treatment of liver disease
  • Amino acid compositions for the treatment of liver disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0274] • Example 1: Treatment of an individual with hepatic insufficiency with an amino acid composition.

[0275] A feature of the studies described herein was the administration of compositions comprising amino acids to individuals with mild to moderate hepatic insufficiency. The purpose of this pre-IND and IRB approved study was to determine the safety and tolerability of the amino acid composition by observing various markers of amino acid metabolism, liver function / health, and ammonia detoxification after 7 and 14 days of administration And its impact on structure and human physiological function. The composition comprises about 0.8889g L-leucine, about 0.4444g L-isoleucine, about 0.8889g L-valine, about 0.4703g L-lysine acetate (or about 0.3333 g L-lysine), about 0.3333 g L-histidine, about 0.3333 g L-threonine, and about 1.6667 g L-ornithine L-aspartate in three stick packs three times a day (eg, a total of about 44.1 g per day or about 14.7 g three times per day) adm...

example 2

[0290] • Example 2: ODLIVHKT increases basal BCAA concentrations.

[0291] Basal plasma concentrations of branched-chain amino acids were determined on days 1 and 20 of treatment in animals treated with ODLIVHKT or the comparator.

[0292] Rationale: Branched-chain amino acids are depleted in plasma of patients with cirrhosis and low levels correlate with end-stage liver disease survival. BCAAs are depleted due to failure of nitrogen processing due to liver failure resulting in catabolism of glutamate used to detoxify ammonia in the muscles. Branched-chain amino acids improve albumin in individuals with hypoalbumin cirrhosis but are ineffective in other aspects of cirrhosis pathophysiology. Valine levels are highly correlated with mortality in cirrhosis (Kinny-Koster 2015).

[0293] Methods: Eight-week-old Sprague-Dawley rats underwent bile duct ligation (BDL), a well-established model of cholestatic-induced cirrhosis. Three weeks after bile duct ligation, the animals were ...

example 3

[0298] • Example 3: Amino Acid Composition Affects Pharmacokinetic Properties of Administered Amino Acids and Prolonged Treatment Leads to Improved Amino Acid Metabolism.

[0299]The pharmacokinetic properties (maximum concentration, CMAX) of ODLIVHKT or the compositional composition were determined on day 1 and day 20.

[0300] Relevance: In cirrhotic individuals, the balance between amino acid catabolism and protein synthesis is disrupted (Muller et al., 1999; Tessari et al., 2003). Responses to anabolic stimuli are attenuated compared to healthy animals, but how the metabolism of specific amino acids is affected based on the amino acid context administered is not known or understood (Tsien et al., 2015). Although LIV and LIVHKT did not prevent deterioration of basal levels of BCAA, and ODLIVHKT treatment increased levels in response to treatment (Example 2), it is unknown how BCAA metabolism is affected by compositions comprising LIV.

[0301] METHODS: Eight-week-old Spreg...

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

No PUM Login to view more

Abstract

Disclosed are compositions comprising branched chain amino acids, urea cycle amino acids and essential amino acids for use in treating or preventing liver diseases and disorders with hyperammonemia ormuscle wasting in a subject.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Application Serial No. 62 / 545,362, filed August 14, 2017, U.S. Application Serial No. 62 / 614,214, filed January 5, 2018, and U.S. Application Serial No. 62 / 697,772; the above-mentioned patent application is hereby incorporated by reference in its entirety. Background technique [0003] An estimated 600,000 people in the United States have liver cirrhosis and 14,000 of these patients are terminally ill and awaiting liver transplantation. Studies have shown that as many as 40-60% of patients with cirrhosis have concomitant muscle wasting. The resulting fragility is a major cause of functional decline, cirrhosis-related complications, hospitalization, and mortality in patients with end-stage liver disease (ESLD). Liver transplantation is definitively curative of ESLD; however, decline in fitness is associated with an increased risk of removal from the transplant waiting list, regardless of l...

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): A61K31/198A61K31/4172A61K38/00A61K9/00A61K45/06A23L2/00A61P1/16A61P21/00A61P31/00A61P43/00
CPCA23L2/00A61K45/06A61K9/145A61K38/03A61K31/198A61P1/16A61K31/17A61K31/4172A61K2300/00A23V2002/00A23L33/18A23L33/17A23V2200/30
Inventor 威廉·康柏肖恩·卡罗尔瑞弗·亚非恩迈克尔·哈米尔
Owner AXCELLA HEALTH INC
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