Formulations for parenteral delivery of compounds and uses thereof

Abstract

The present invention provides formulations that achieve effective delivery of methylnaltrexone compositions. The provided formulations are useful for preventing, treating delaying, diminishing or reducing the severity of side effects resulting from use of analgesic opioids.

1 - 38 . (canceled) 
     
     
         39 . A method of preparing a methylnaltrexone formulation for parenteral administration, the method comprising the steps of:
 preparing a solution comprising methylnaltrexone or a pharmaceutically acceptable salt thereof, an isotonic agent and a calcium salt chelating agent; and   sterilizing the resulting solution and distributing to one or more sealed containers.   
     
     
         40 . The method of  claim 39 , wherein the calcium salt chelating agent is selected from the group calcium ethylenediaminetetraacetic acid (EDTA), calcium diethylenetriaminepentaacetic acid (DTPA), calcium hydroxyethylenediaminetriacetic acid (HEDTA), calcium ethylene glycol-bis-(2-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA), calcium nitrilotriacetic acid (NTA), calcium citrate, and calcium salt derivatives thereof. 
     
     
         41 . The method of  claim 39  wherein the active compound is methylnaltrexone bromide. 
     
     
         42 . The method of  claim 39 , wherein the solution comprises an isotonic agent. 
     
     
         43 . The method of  claim 42  wherein the isotonic agent is selected from the group consisting of sodium chloride, mannitol, lactose, dextrose, glycerol, and sorbitol. 
     
     
         44 . The method of  claim 43 , wherein the isotonic agent comprises a delivery vehicle selected from the group consisting of 5% Dextrose, Lactated Ringer's Injection and 0.65% NaCl and 0.9% NaCl. 
     
     
         45 . The method of  claim 39 , wherein the solution comprises water for injection. 
     
     
         46 . The method of  claim 39 , wherein the calcium salt chelating agent is calcium ethylenediaminetriacetic acid (EDTA) or calcium ethylene glycol-bis-(2-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA) or a calcium salt derivative thereof. 
     
     
         47 . The method of  claim 39  wherein the solution comprises a stabilizing agent. 
     
     
         48 . The method of  claim 47 , wherein the stabilizing agent is glycine. 
     
     
         49 . The method of  claim 48 , wherein an effective amount of glycine maintains pH at about 3.0 to about 4.0. 
     
     
         50 . The method of  claim 49 , wherein the pH is about 3.5. 
     
     
         51 . A method of preparing a methylnaltrexone formulation, the method comprising the steps of:
 preparing a solution comprising methylnaltrexone or a pharmaceutically acceptable salt thereof, an isotonic agent, a calcium salt chelating agent and a stabilizing agent;   
       adjusting the pH of the solution to between pH 2.0 and pH 6.0; and
 sterilizing the resulting solution and distributing to one or more sealed containers. 
 
     
     
         52 . The method of  claim 51 , wherein the calcium salt chelating agent is selected from the group calcium ethylenediaminetetraacetic acid (EDTA), calcium diethylenetriaminepentaacetic acid (DTPA), calcium hydroxyethylenediaminetriacetic acid (HEDTA), calcium ethylene glycol-bis-(2-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA), calcium nitrilotriacetic acid (NTA), calcium citrate, and calcium salt derivatives thereof. 
     
     
         53 . The method of  claim 51 , wherein the active compound is methylnaltrexone bromide. 
     
     
         54 . The method of  claim 51 , wherein the isotonic agent is selected from the group consisting of sodium chloride, mannitol, lactose, dextrose, glycerol, and sorbitol. 
     
     
         55 . The method of  claim 54 , wherein the isotonic agent comprises a delivery vehicle selected from the group consisting of 5% Dextrose, Lactated Ringer's Injection and 0.65% NaCl and 0.9% NaCl. 
     
     
         56 . The method of  claim 51 , wherein the aqueous solution comprises water for injection. 
     
     
         57 . The method of  claim 52 , wherein the calcium salt chelating agent is calcium ethylenediaminetriacetic acid (EDTA) or calcium ethylene glycol-bis-(2-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA), or a calcium salt derivative thereof. 
     
     
         58 . The method of  claim 51 , wherein the stabilizing agent is glycine. 
     
     
         59 . The method of  claim 58 , wherein the glycine is glycine-HCl. 
     
     
         60 . The method of  claim 51 , wherein an effective amount of glycine maintains pH at about 3.0 to about 4.0. 
     
     
         61 . The method of  claim 60 , wherein the pH is about 3.5. 
     
     
         62 - 70 . (canceled)