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.

1 . A pharmaceutical composition for the treatment or prevention of hyperammonemia comprising PEG and lactulose in an amount from about 0.5 to 3 parts by weight polyethylene glycol (PEG) to about  1  part by weight lactulose.  
   
   
       2 . A single dosage of the composition of  claim 1  comprising about 5 to 35 gm of PEG.  
   
   
       3 . The single dosage composition of  claim 2 , comprising about 10 to 30 gm of lactulose.  
   
   
       4 . The single dosage composition of  claim 3 , comprising about 10 to 20 gm PEG and 10 to 20 gm lactulose.  
   
   
       5 . A composition according to  claim 1 , wherein the PEG is solid at room temperature.  
   
   
       6 . A composition according to  claim 3 , wherein the PEG is solid at room temperature.  
   
   
       7 . A composition according to  claim 1 , wherein the lactulose and PEG are each a dry powder.  
   
   
       8 . A composition according to  claim 3 , wherein the lactulose and PEG are each a dry powder.  
   
   
       9 . A composition according to  claim 4 , wherein the lactulose and PEG are each a dry powder.  
   
   
       10 . A composition according to  claim 1 , wherein the composition is free of serum electrolytes.  
   
   
       11 . A composition according to  claim 3 , wherein the composition is free of serum electrolytes.  
   
   
       12 . The composition of  claim 1 , wherein the patient has, or is at risk of, HE characterized by hyperammonemia.  
   
   
       13 . The composition of  claim 3 , wherein the patient has, or is at risk of, HE characterized by hyperammonemia.  
   
   
       14 . A pharmaceutical composition according to  claim 1 , wherein the composition further includes at least one probiotic or prebiotic or a mixture thereof.  
   
   
       15 . The composition of  claim 14 , wherein the composition comprises at least one probiotic selected from  Bacteriodes, Lactobacillus, Clostridium, Fusobacterium, Bifidobacterium, Eubacterium, Peptococcus, Peptostreptococcus, Escherichia,  and  Veillonella.    
   
   
       16 . The composition of  claim 15 , wherein at least one probiotic is a strain of  Lactobacillus  or  Bifidobacterium  or a mixture thereof, and at least one prebiotic, if present, is a stimulant for the selected strain or strains.  
   
   
       17 . A method for the treatment of a patient with hyperammonemia, comprising orally administering to the patient a pharmaceutical composition free of serum electrolytes and comprising from about 0.15 to 3.5 parts by weight PEG to about 1 part by weight lactulose and at least one probiotic or prebiotic, or a mixture thereof, in an amount and frequency sufficient to reduce patient plasma ammonia to a clinically-acceptable level or to maintain this level, or both.  
   
   
       18 . The method of  claim 17 , wherein the composition comprises from about 0.5 to 3 parts by weight PEG to 1 part by weight lactulose.  
   
   
       19 . The method of  claim 17 , wherein the composition is administered in single dosages each comprising about 5 to 35 gm of dry PEG dissolved in the aqueous carrier.  
   
   
       20 . The method of  claim 19 , wherein each single dosage further comprises about 10 to 30 gm of dry lactulose dissolved in the aqueous carrier.  
   
   
       21 . The method of  claim 20 , wherein each single dosage comprises about 10 to 20 gm PEG and about 10 to 20 gm lactulose dissolved in the aqueous carrier.  
   
   
       22 . The method of  claim 17 , wherein the composition is a dry composition formulated as a liquid drink by admixture with a pharmaceutically-acceptable aqueous carrier.  
   
   
       23 . The method of  claim 17 , wherein the composition comprises at least one probiotic selected from  Bacteriodes, Lactobacillus, Clostridium, Fusobacterium, Bifidobacterium, Eubacterium, Peptococcus, Peptostreptococcus, Escherichia,  and  Veillonella.    
   
   
       24 . The composition of  claim 23 , wherein at least one probiotic is a strain of  Lactobacillus  or  Bifidobacterium  or a mixture thereof, and at least one prebiotic, if present, is a stimulant for a selected strain or strains.