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.

We claim: 
     
         1 . A pharmaceutical composition comprising an effective amount of methylnaltrexone or a pharmaceutically acceptable salt thereof, calcium ethylenediaminetriacetic acid (EDTA) or a calcium salt EDTA derivative, and glycine in an aqueous solution, wherein the solution has a pH of about 3 to 4, and wherein the composition further comprises at least one opioid. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the salt of methylnaltrexone comprises methylnaltrexone bromide. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the composition comprises about 5 mg to about 40 mg of methylnaltrexone or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the composition comprises about 8 mg to about 12 mg of methylnaltrexone or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the composition comprises about 10 mg/mL to about 20 mg/mL methylnaltrexone bromide. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the composition comprises about 0.2 mg/mL to about 0.8 mg/mL of the calciumethylenediaminetriacetic acid (EDTA) or the calcium salt EDTA derivative. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the composition comprises about 0.1 mg/mL to about 0.8 mg/mL of the glycine. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the calcium salt EDTA derivative comprises calcium EDTA disodium. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the glycine comprises glycine HCl. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the solution has a pH of about 3.4 to about 3.6. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the solution has a pH of about 3.5. 
     
     
         12 . The pharmaceutical composition of  claim 1 , further comprising sodium chloride. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the at least one opioid comprises alfentanil, anileridine, asimadoline, bremazocine, burprenorphine, butorphanol, codeine, dezocine, diacetylmorphine (heroin), dihydrocodeine, diphenoxylate, ethylmorphine, fedotozine, fentanyl, funaltrexamine, hydrocodone, hydromorphone, levallorphan, levomethadyl acetate, levorphanol, loperamide, meperidine (pethidine), methadone, morphine, morphine-6-glucoronide, nalbuphine, nalorphine, nicomorphine, opium, oxycodone, oxymorphone, papaveretum, pentazocine, propiram, propoxyphene, remifentanyl, sufentanil, tilidine, trimebutine, or tramadol. 
     
     
         14 . A method for relieving pain and reducing a side effect of opioid treatment in a subject, comprising administering the pharmaceutical composition of  claim 1  to the subject. 
     
     
         15 . The method of  claim 14 , wherein the side effect is opioid induced constipation. 
     
     
         16 . The method of  claim 14 , wherein the salt of methylnaltrexone comprises methylnaltrexone bromide. 
     
     
         17 . The method of  claim 14 , wherein the composition comprises about 5 mg to about 40 mg of methylnaltrexone or a pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 17 , wherein the composition comprises about 8 mg to about 12 mg of methylnaltrexone or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 16 , wherein the composition comprises about 10 mg/mL to about 20 mg/mL methylnaltrexone bromide. 
     
     
         20 . The method of  claim 14 , wherein a subject weighing between 38 kg and 62 kg is administered a dose of about 8 mg methylnaltrexone or a pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 14 , wherein a subject weighing between 62 kg and 114 kg is administered a dose of about 12 mg of methylnaltrexone or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 14 , wherein a subject weighing less than 38 kg or greater than 114 kg is administered a dose of about 0.15 mg/kg of methylnaltrexone or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The method of  claim 14 , wherein the subject is administered a dose every day or every other day.