Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy
View Patent ↗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.
1. A method of treating hepatic encephalopathy, comprising administering to a patient in need thereof a single pharmaceutical composition comprising ornithine and at least one of phenylacetate or phenylbutyrate, wherein the dosage of ornithine administered is from 1 g to 50 g and the dosage of phenylacetate or phenylbutyrate administered is from 1 g to 50 g and the weight ratio of ornithine to phenylacetate or phenylbutyrate in the composition is from 2:1 to 1:2 and the amounts administered are effective to reduce, or attenuate an increase in, blood ammonia in said patient, wherein the patient has chronic liver disease or acute liver failure, wherein the pharmaceutical composition comprises substantially no other amino acid.
2. The method of claim 1 , wherein the administration ameliorates one or more symptoms of the hepatic encephalopathy.
3. The method of claim 1 , wherein the pharmaceutical composition comprises substantially no aspartate.
4. The method of claim 1 , wherein the pharmaceutical composition comprises no aspartate.
5. The method of claim 1 , wherein the pharmaceutical composition comprises no other amino acid.
6. The method of claim 1 , wherein the pharmaceutical composition consists essentially of ornithine and at least one of phenylacetate and phenylbutyrate.
7. The method of claim 1 , wherein from 0.02 g/kg to 1.25 g/kg of ornithine and from 0.02 g/kg to 1.25 g/kg of phenylacetate or phenylbutyrate is administered to said patient.
8. The method of claim 1 , wherein from 0.1 g/kg to 0.5 g/kg of ornithine and from 0.1 g/kg to 0.5 g/kg of phenylacetate or phenylbutyrate is administered to said patient.
9. The method of claim 1 , wherein from 5 g to 30 g of ornithine and from 5 g to 30 g of at least one of phenylacetate or phenylbutyrate are administered to said patient.
10. A method according to claim 1 wherein said ornithine is present as a free monomeric amino acid or physiologically acceptable salt.
11. A method according to claim 1 wherein the at least one of phenylacetate and phenylbutyrate is present as sodium phenylacetate or sodium phenylbutyrate.
12. A method according to claim 1 wherein said administration is intravenous, intraperitoneal, intragastric, intravascular or oral administration.
13. The method of claim 1 , wherein the effective amount of ornithine and at least one of phenylacetate and phenylbutyrate is administered to a patient having chronic liver disease.
14. The method of claim 13 , wherein the effective amount of ornithine and at least one of phenylacetate and phenylbutyrate is administered to a patient having liver cirrhosis.
15. The method of claim 1 , wherein the effective amount of ornithine and at least one of phenylacetate and phenylbutyrate is administered to a patient having acute liver failure.
16. A method of reducing the likelihood of the onset of, or delaying the onset of, hepatic encephalopathy, comprising administering to a patient at risk thereof a single pharmaceutical composition comprising ornithine and at least one of phenylacetate or phenylbutyrate, wherein the dosage of ornithine administered is from 1 g to 50 g and the dosage of phenylacetate or phenylbutyrate administered is from 1 g to 50 g and the weight ratio of ornithine to phenylacetate or phenylbutyrate in the composition is from 2:1 to 1:2 and the amounts administered are effective to reduce, or attenuate an increase in, blood ammonia in said patient, wherein the patient has chronic liver disease or acute liver failure, wherein the pharmaceutical composition comprises substantially no other amino acid.
17. A method of claim 16 , wherein said ornithine is present as a free monomeric amino acid or physiologically acceptable salt.
18. A method of claim 16 , wherein the at least one of phenylacetate and phenylbutyrate is present as sodium phenylacetate or sodium phenylbutyrate.
19. A method of claim 16 , wherein said administration is intravenous, intraperitoneal, intragastric, intravascular or oral administration.
20. The method of claim 16 , wherein the effective amount of ornithine and at least one of phenylacetate and phenylbutyrate is administered to a patient having chronic liver disease.
21. The method of claim 20 , wherein the effective amount of ornithine and at least one of phenylacetate and phenylbutyrate is administered to a patient having liver cirrhosis.
22. The method of claim 16 , wherein the effective amount of ornithine and at least one of phenylacetate and phenylbutyrate is administered to a patient having acute liver failure.
23. The method of claim 16 , wherein the pharmaceutical composition comprises no aspartate.
24. The method of claim 16 , wherein the pharmaceutical composition comprises substantially no aspartate.
25. The method of claim 16 , wherein the pharmaceutical composition comprises no other amino acid.
26. The method of claim 16 , wherein the pharmaceutical composition consists essentially of ornithine and at least one of phenylacetate and phenylbutyrate.
27. The method of claim 16 , wherein from 0.02 g/kg to 1.25 g/kg of ornithine and from 0.02 g/kg to 1.25 g/kg of phenylacetate or phenylbutyrate is administered to said patient.
28. The method of claim 16 , wherein from 0.1 g/kg to 0.5 g/kg of ornithine and from 0.1 g/kg to 0.5 g/kg of phenylacetate or phenylbutyrate is administered to said patient.
29. The method of claim 16 , wherein from 5 g to 30 g of ornithine and from 5 g to 30 g of at least one of phenylacetate or phenylbutyrate are administered to said patient.
30. A method according to claim 16 wherein the patient has had or is suspected of having had a precipitating event.
31. A method according to claim 30 , wherein said precipitating event is gastrointestinal bleeding, infection, portal vein thrombosis or dehydration.
32. A method according to claim 30 , wherein the ornithine and at least one of phenylacetate and phenylbutyrate is administered within 6 hours of a symptom(s) of said precipitating event or suspected precipitating event having been detected.
33. The method of claim 16 , wherein the administration reduces the likelihood of onset of hepatic encephalopathy.