Continuous Administration of L-Dopa, Dopa Decarboxylase Inhibitors, Catechol-O-Methyl Transferase Inhibitors and Compositions for Same

Abstract

Provided herein, in part, is a method of treating a neurological or movement disorder in a patient in need thereof, comprising subcutaneously administering to said patient a pharmaceutically acceptable composition comprising levodopa and optionally carbidopa and optionally entacapone or tolcapone, or pharmaceutically acceptable salts thereof, wherein said composition is administered substantially continuously, and compositions that can be used in the disclosed methods.

1 . A pharmaceutically acceptable composition having a pH of about 9.1 to about 9.8 at 25° C., comprising:
 active components comprising carbidopa and at least about 4% by weight levodopa; arginine and optionally meglumine. 
 
     
     
         2 . The pharmaceutically acceptable composition of  claim 1 , wherein the molar ratio of active components to the arginine is about 1:1.8 to about 1:3.5. 
     
     
         3 . The pharmaceutically acceptable composition of  claim 1 , comprising about 4% to about 12% by weight levodopa. 
     
     
         4 . The pharmaceutically acceptable composition of  claim 1 , comprising about 1% to about 6% by weight carbidopa. 
     
     
         5 . The pharmaceutically acceptable composition of  claim 1 , comprising meglumine. 
     
     
         6 . The pharmaceutically acceptable composition of  claim 5 , wherein the molar ratio of active components to the arginine is about 1:1.1 to about 1:1.9, and the molar ratio of active components to the meglumine is about 1:0.3 to about 1:1.5. 
     
     
         7 . The pharmaceutically acceptable composition of  claim 5 , wherein the molar ratio of active components to the meglumine is about 1:0.3 to about 1:1.2. 
     
     
         8 . The pharmaceutically acceptable composition of  claim 5 , wherein the composition comprises about 2.0% to about 11% by weight meglumine. 
     
     
         9 . The pharmaceutically acceptable composition of  claim 1 , comprising about 10% to about 35% by weight arginine. 
     
     
         10 . The pharmaceutically acceptable composition of  claim 1 , further comprising an agent that inhibits the formation of oxidation products. 
     
     
         11 . The pharmaceutically acceptable composition of  claim 10 , wherein the agent is selected from ascorbic acid, Na-ascorbate, L-cysteine, N-acetylcysteine (NAC), glutathione (GSH), Na 2 -EDTA, Na 2 -EDTA-Ca, or combinations thereof. 
     
     
         12 . The pharmaceutically acceptable composition of  claim 10 , wherein said agent is ascorbic acid or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The pharmaceutically acceptable composition of  claim 1 , further comprising sodium bisulfate. 
     
     
         14 . A pharmaceutically acceptable composition comprising levodopa, arginine and optionally meglumine; and further comprising ascorbic acid or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The pharmaceutically acceptable composition of  claim 14 , wherein the ascorbic acid salt is selected from ascorbate, sodium ascorbate, calcium ascorbate, potassium ascorbate, ascorbyl palmitate, or ascorbyl stearate. 
     
     
         16 . The pharmaceutically acceptable composition of  claim 14 , comprising about 0.5% to about 1%, by weight ascorbic acid or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The pharmaceutically acceptable composition of  claim 14 , wherein the molar ratio of levodopa to the arginine is about 1:2.3. 
     
     
         18 . The pharmaceutically acceptable composition of  claim 17 , comprising about 4% to about 12% by weight levodopa. 
     
     
         19 - 25 . (canceled) 
     
     
         26 . A transdermal patch suitable for administering a pharmaceutically acceptable composition according to  claim 1 . 
     
     
         27 . A method of treating a neurological or movement disorder in a patient in need thereof, the method comprising the steps of:
 (a) substantially continuously administering to said patient a composition of  claim 1 , wherein the composition is administered subcutaneously, intraduodenally or intravenously; and   (b) orally administering levodopa and/or carbidopa and optionally entacapone or tolcapone.   
     
     
         28 - 30 . (canceled) 
     
     
         31 . The method of  claim 27 , wherein the composition is administered subcutaneously using one or more infusion pumps and/or transdermal and/or dermal patches. 
     
     
         32 . (canceled) 
     
     
         33 . The method of  claim 27 , wherein the rate of administering the composition is about 1.0±0.5 ml/hour during the day or during patient activity, and about 0 to about 0.5 ml/hour at night or at rest. 
     
     
         34 . The method of  claim 27 , wherein the disorder is Parkinson's disease. 
     
     
         35 . A pharmaceutically acceptable formulation comprising about 2.5 to about 7% by weight levodopa, about 0 to about 2% by weight carbidopa, about 5 to about 18% by weight arginine, and about 0.25% to about 3% by weight ascorbic acid or a pharmaceutically acceptable salt thereof. 
     
     
         36 - 47 . (canceled)