Generated: April 28, 2017
|Title:||Pharmaceutical compositions for the treatment of hereditary tyosinemia type I|
|Abstract:||The invention concerns novel pharmaceutical compositions containing as an active ingredient a 2-benzoyl-1,3-cyclohexanedione which is an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD). The compositions are valuable in the treating those disorders and diseases in which it is desirable to intervene in the metabolic sequences catalysed by HPPD, such as in treating tyrosinemia type I.|
|Inventor(s):||Ellis; Martin K. (Macclesfield, GB2), Lindstedt; Sven T. (Lund, SE), Lock; Edward A. (Wilmslow, GB2), Markstedt; Maj E. H. (Billdal, SE), Mutter; Linda C. (Bloomfield, CA), Prisbylla; Michael P. (Richmond, CA)|
|Assignee:||Zeneca Limited (London, GB2)|
1. A pharmaceutical composition comprising as an active ingredient an effective 4-hydroxyphenypyruvate dioxygenase inhibiting amount of the compound
2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable diluent or carrier.
2. A composition as claimed in claim 1 wherein the active ingredient is selected from an alkali metal salt, alkaline earth metal salt, ammonium salt, and a salt with an organic base giving a physiologically acceptable cation, of the compound 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione.
3. A composition as claimed in claim 1 or 2 which is in a form suitable for oral, parenteral or rectal administration.
4. A composition as claimed in claim 1 or 2 which is in a palatable form suitable for oral administration selected from tablets, lozenges, hard capsules, soft capsules, aqueous suspensions, oily suspensions, emulsions, dispersible powders, dispersible granules, syrups and elixirs.
5. A composition as claimed in claim 1 or 2 which is in a form suitable for parenteral administration selected from sterile aqueous and oily solutions.
6. A method of treating multi-organ symptoms in human patients caused by hereditary tyrosinaemia in which intervention in the metabolic sequences catalysed in part by the enzyme 4-hydroxyphenylpyruvate dioxygenase is desirable which comprises the administration of an effective amount of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexandione, or a pharmaceutically acceptable salt thereof.
7. A method for the treatment of the disease condition known as hereditary tyrosinaemia in a warm blooded animal which comprises the administration of an effective amount of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, or of a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition according to claim 1 wherein the pharmaceutically acceptable carrier is selected from Lactose Ph.Eur; croscarmellose sodium; maize starch, polyvinylpyrrolidone or magnesium stearate.
9. A method of inhibiting the catalytic activity of the enzyme 4-hydroxyphenylpyruvate dioxygenase comprising the administration to a human patient in need of treatment thereof suffering from hereditary tyrosinaemia and associated symptoms a therapeutically effective amount of the compound 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexandione or a pharmaceutically acceptable salt thereof.
10. A method of treating hereditary tyrosinaemia in human patients wherein the products of the catalytic action of the enzyme HPPD are involved or implicated comprising the administration of a pharmaceutically effective amount of the compound 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione or a pharmaceutically acceptable salt thereof.
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