JP2018533601A5 - - Google Patents

Claims (20)

An oral pharmaceutical formulation comprising an oral dosage of 2 g to 10 g of L-ornithine phenylacetate and one or more pharmaceutically acceptable excipients or carriers. The oral pharmaceutical formulation according to claim 1, wherein the oral dose of L-ornithine phenyl acetate is 2 g to 6 g. The oral dosage of L- ornithine phenylacetate is 2 g to 4 g, the oral pharmaceutical formulation according to claim 1. 4. The oral pharmaceutical formulation according to any one of claims 1 to 3 , which is in a single unit dosage form. The oral pharmaceutical formulation according to any one of claims 1 to 3 , which is in two or more unit dosage forms. 6. The oral pharmaceutical formulation according to claim 5, having 2 to 5 unit dosage forms, each containing 0.5 g to 2 g of L-ornithine phenyl acetate. The oral pharmaceutical formulation according to any one of claims 4 to 6 , wherein the unit dosage form is a tablet, capsule, pill, pellet, flowable powder, or liquid. The oral pharmaceutical formulation according to any one of claims 1 to 7, which provides an immediate release profile of L-ornithine phenyl acetate upon oral administration. To an oral pharmaceutical formulation according to any one of claims 1 to 8 for the treatment or amelioration of hyperammonemia, wherein the preparation is in oral administration, 10μg / mL~ 1 50μg / mL , The oral pharmaceutical formulation , wherein the oral pharmaceutical formulation results in a plasma Cmax of phenylacetic acid ranging from 20 μg / mL to 140 μg / mL, 30 μg / mL to 130 μg / mL, or 40 μg / mL to 120 μg / mL . Wherein the preparation is in oral administration, 5 μg / mL~ 1 00μg / mL, 10μg / mL~80μg / mL, 20μg / mL~60μg / mL or 25μg / mL~50μg / mL range of phenylacetylglutamine, The oral pharmaceutical formulation according to claim 9 , which produces a plasma Cmax of Before SL formulation, upon oral administration, 1 00hr * μg / mL~ 1 000hr * μg / mL, 200hr * μg / mL~800hr * μg / mL, 350hr * μg / mL~600hr * μg / mL or, An oral pharmaceutical formulation according to claim 9 or 10 , which provides a plasma AUC _0-t or AUC _0-inf of phenylacetic acid in the range of 400 hr * μg / mL to 550 hr * μg / mL . Plasma _{AUC 0-t} and _{AUC 0-inf} of phenylacetyl glutamine, 2 5hr * μg / mL~ 5 00hr * μg / mL, 50hr * μg / mL~300hr * μg / mL, 100hr * μg / mL~200hr * The oral pharmaceutical formulation according to claim 11 , wherein the oral pharmaceutical formulation has a g / mL or 120 hr * g / mL to 180 hr * g / mL . Plasma _{AUC 0-inf} of phenylacetyl glutamine, 5 0hr * μg / mL~ 4 00hr * μg / mL, 75hr * μg / mL~300hr * μg / mL, 100hr * μg / mL~250hr * μg / mL or, The oral pharmaceutical preparation according to claim 11 , wherein the oral pharmaceutical preparation has a viscosity of 150 hr * μg / mL to 200 hr * μg / mL . Target is acute liver failure, chronic liver disease, hepatic decompensation with, and Child-Pugh class A, B or one or more selected from the group consisting of cirrhosis with classification of C,, claim 9 13 An oral pharmaceutical preparation according to any one of the preceding claims . Target has a hepatic encephalopathy or portal hypertension, oral pharmaceutical formulation according to any one of claims 9 14. Having Target urea cycle disorders, oral pharmaceutical formulation according to any one of claims 9 13. The oral pharmaceutical formulation is administered more than once a day, oral pharmaceutical formulation according to any one of claims 9 16. 18. The oral pharmaceutical formulation according to claim 17, wherein the oral pharmaceutical formulation is administered three times a day. The formulation results in the conversion of 5 0% of phenyl acetate in 24 hours to phenylacetylglutamine, oral pharmaceutical formulation according to any one of claims 9 18. 20. The oral pharmaceutical formulation of claim 19 , wherein the formulation results in greater than 80 % conversion of phenylacetate to phenylacetylglutamine in 24 hours.