Formulations for parenteral delivery of compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2020179270-A1
Application number	US-201916514722-A
Country	US
Kind code	A1
Filing date	Jul 17, 2019
Priority date	Aug 4, 2006
Publication date	Jun 11, 2020
Grant date	—

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.

First claim

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)

Assignees

• Wyeth Llc

Inventors

• Shah Syed M
• Ofslager Christian
• Fawzi Mahdi B
• Bazhina Nataliya

Classifications

• A61K47/02

  Inorganic compounds · CPC title

• A61K31/485

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• A61K9/08 Primary

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title