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Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy

A technology of phenylbutyric acid and phenylacetic acid, which can be used in medical preparations containing active ingredients, drug combinations, organic active ingredients, etc., and can solve problems such as shortening lifespan

Active Publication Date: 2008-01-09
UCL BUSINESS PLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Prevention of hepatic decompensation is highly desirable due to shortened lifespan due to hepatic decompensation

Method used

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  • Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy
  • Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy
  • Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0108] Example 1: Altered neutrophil function in patients with cirrhosis and progression with progressive liver disease change

[0109] Methods for Measuring Neutrophil Phagocytosis and Oxidative Burst

[0110] Phagocytosis assay: Heparinized whole blood was incubated with opsonized FITC-labeled E. coli and CD16. Cells were then analyzed by flow cytometry (FACScan Becton Dickinson), gating by forward and side scatter, followed by phycoerythrin (PE) [Immunotech, Marseille, France] fluorescent dye expression. Assess to identify CD16 positive cells. The gated cell populations were then evaluated for the presence of FITC-labeled bacteria.

[0111] Phagocytic Burst: Heparinized whole blood was incubated with an opsonized E. coli suspension to elicit an oxidative burst. The substrate solution was added to measure the conversion of dihydrorhodamine (DHR) 123 to the fluorescent source compound rhodamine (R) 123 . Reactions were stopped and fixed, then incubated with CD16 antibo...

Embodiment 2

[0117] Example 2: Ammonia reduces the phagocytosis of neutrophils

[0118] Methods for Measuring Phagocytosis and Oxidative Burst of Neutrophils

[0119] As described in Example 1.

[0120] patients and methods

[0121] Blood was collected from healthy volunteers (n=15) and incubated with increasing concentrations of ammonia for 1 hour. The ability of neutrophils to phagocytose bacteria was determined by phagocytosis assay and neutrophil chemotaxis assay. IL-8 at 10 ng / ml was used in the neutrophil chemotaxis assay.

[0122] result

[0123] Phagocytosis of neutrophils (Fig. 2) and chemotaxis of neutrophils (Fig. 3) were significantly attenuated as the concentration of ammonia in the culture was increased.

Embodiment 3

[0124] Example 3: The effect of ammonia on neutrophil phagocytosis can be reversed by intervention

[0125] Methods for Measuring Phagocytosis and Oxidative Burst of Neutrophils

[0126] As described in Example 1.

[0127] patients and methods

[0128] Blood was collected from healthy volunteers (n=15) and incubated with ammonia and selected amino acids for 1 hour. The ability of neutrophils to phagocytose bacteria was determined by phagocytosis assay.

[0129] result

[0130] We observed that ammonia-induced attenuation of neutrophil phagocytosis was partially reversed by ornithine and glutamine (Fig. 4). However, co-incubation with ammonia and aspartic acid worsened neutrophil phagocytosis, which remained unchanged when L-ornithine was used.

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PUM

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Abstract

The present invention relates to use of ornithine in the manufacture of a medicament for use in combination with at least one of phenylacetate and phenylbutyrate for preventing or treating liver decompensation or hepatic encephalopathy. The invention also relates to use of at least one of phenylacetate and phenylbutyrate in the manufacture of a medicament for use in combination with ornithine for preventing or treating liver decompensation or hepatic encephalopathy.

Description

technical field [0001] The present invention relates to the prevention and treatment of hepatic decompensation or hepatic encephalopathy. Background technique [0002] Chronic liver disease is characterized by the progressive destruction of liver tissue over time, resulting in the slow replacement of healthy and regenerating liver tissue with scar tissue and dead tissue. This phenomenon is known as cirrhosis. Normal liver function is impaired, and scar tissue gradually reduces blood flow in the liver. With the loss of normal regenerating liver tissue, nutrients, hormones, drugs and toxins are no longer efficiently processed. [0003] This can lead to a variety of symptoms, including: abnormal clearance of absorbed proteins through the gut leading to ammonia accumulation; abnormal secretion leading to accumulation of bilirubin in the blood, producing jaundice; increased sinus pressure leading to accumulation of fluid in the abdomen (ascites); and Portal hypertension (porto...

Claims

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Application Information

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IPC IPC(8): A61P1/16A61K31/192A61K31/198
Inventor R·贾兰K·N·贾兰
Owner UCL BUSINESS PLC
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