Composition and method for treatment of hepatic encephalopathy

Abstract

The inventions provide an improved treatment for hepatic encephalopathy characterized by hyperammonemia and / or constipation, comprising the oral administration of polyethylene glycol (PEG) in amounts sufficient to reduce plasma levels of ammonia and / or to alleviate constipation. Preferably, the PEG is administered in combination with lactulose, which provides a palatable composition for the treatment of HE with excellent therapeutic benefits and reduced side effects as compared to lactulose alone.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. patent application Ser. No. 10 / 748,185, filed Dec. 31, 2003.BACKGROUND OF THE INVENTION [0002] 1. Field of Art [0003] Hepatic encephalopathy (HE) is a syndrome associated with liver dysfunction, characterized by a decline in mental function and neurological abnormalities. Distinctive clinical signs include personality changes and intellectual impairment, and neuromuscular anomalies such as asterixis (flapping tremor) and alterations in gait. [0004] The syndrome typically manifests in patients with an extensive collateral blood vessel system (extrahepatic portal shunts) which diverts portal venous blood away from the liver into the systemic circulation. Thus, toxic metabolites absorbed into the bloodstream from the intestines may largely bypass the liver and enter the general circulatory system without being detoxified. Among other ramifications, such toxins can cause metabolic aberratio...

AI Technical Summary

Benefits of technology

[0009] The inventions provide an improved treatment for hepatic encephalopathy characterized by hyperammonemia and / or constipation, comprising the oral administration of polyethylene glycol (PEG) in amounts sufficient to reduce plasma levels of ammonia and / or to alleviate constipation. Preferably, the PEG is administered in combination with lactulose, which provides a palatable composition for the treatment of HE with excellent therapeutic benefits and reduced side effects as compared to lactulose alone.

Problems solved by technology

If the liver is sufficiently diseased, or bypassed as when portal shunts are present, plasma levels of ammonia may increase to toxic levels, affecting, for example, the transport of amines, water, and electrolytes across the neuronal membrane.

However, it is very difficult to obtain compliance from patients for several reasons, mainly that current lactulose formulations have a very bad taste, and that at the required dosages they frequently cause bloating and nausea to the point of significant discomfort.