Claims for Patent: 7,977,324

Summary for Patent: 7,977,324

Title:	Process for preparing malathion for pharmaceutical use
Abstract:	The present invention provides a process for preparing a highly pure form of malathion having a reduced level of toxic impurities. In addition, the malathion prepared by the process of this invention is storage stable. The level of toxic impurities in the malathion, e.g., isomalathion, O,O,S-trimethyl phosphorodithioate (MeOOSPS), O,O,S-trimethyl phosphorothioate (MeOOSPO), O,S,S-trimethyl phosphorodithioate (MeOSSPO), malaoxon, isomalathion, diethyl fumarate, methyl malathion, dimethyl malathion, O,O-methyl,ethyl-S-(1,2-dicarboethoxy)ethyl-phosphorodithioate are lower than that of any other commercial preparation of malathion that may be used for pharmaceutical purposes.
Inventor(s):	Gutman; Daniella (Rishon Lezion, IL), Baidussi; Wael (Hamisholash, IL)
Assignee:	Taro Pharmaceuticals North America, Inc. (Cayman, KY)
Application Number:	12/353,691
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,977,324
Patent Claims:	1. A pharmaceutical formulation comprising pharmaceutical grade malathion, said pharmaceutical grade malathion containing 0.1% or less (w/w) MeOOSPO, 0.1% or less (w/w) MeOSSPO, 0.2% or less (w/w) MeOOSPS, less than 0.1% (w/w) methyl malathion, 0.1% or less (w/w) malaoxon and 0.1% or less (w/w) isomalathion. 2. The pharmaceutical formulation of claim 1, comprising pharmaceutical grade malathion having a purity of greater than 99% (w/w). 3. The pharmaceutical formulation of claim 1 wherein the malathion in the formulation contains 0.05% or less (w/w) MeOOSPO. 4. The pharmaceutical formulation of claim 1 wherein the malathion in the formulation contains 0.04% or less (w/w) MeOOSPO. 5. The pharmaceutical formulation of claim 1 wherein the malathion in the formulation contains 0.02% or less (w/w) MeOSSPO. 6. The pharmaceutical formulation of claim 1, comprising pharmaceutical grade malathion containing not more than about 0.1% (w/w) of any other detectable impurity. 7. The pharmaceutical formulation of claim 1, wherein the malathion in the formulation contains 0.08% or less (w/w) methyl malathion. 8. The pharmaceutical formulation of claim 1, wherein the malathion in the formulation contains 0.06% or less (w/w) methyl malathion. 9. The pharmaceutical formulation of claim 1, wherein the malathion in the formulation contains 0.05% or less (w/w) isomalathion. 10. The pharmaceutical formulation of claim 1, wherein the malathion in the formulation contains 0.02% or less (w/w) isomalathion. 11. The pharmaceutical formulation of claim 1, wherein the malathion in the formulation contains 0.2% or less (w/w) diethyl fumarate and 0.2% or less (w/w) dimethylmalathion. 12. The formulation of claim 1, wherein the malathion in the formulation contains less than 0.05% (w/w) malaoxon. 13. The pharmaceutical formulation of claim 1 wherein the malathion in the formulation contains 0.1% or less (w/w) MeOOSPS. 14. The pharmaceutical formulation of claim 1, wherein the amount of isomalathion is not more than 0.1% (w/w), after storage for 3 months at 25.degree. C. and 60% relative humidity. 15. The pharmaceutical formulation of claim 1, wherein the amount of isomalathion is not more than 0.1% (w/w), after storage for 3 months at 30.degree. C. and 60% relative humidity. 16. The pharmaceutical formulation of claim 1, wherein the amount of isomalathion is not more than 0.1% (w/w), after storage for 3 months at 40.degree. C. and 75% relative humidity. 17. A pharmaceutical formulation comprising at least 0.5% (w/w) malathion wherein the malathion contains less than 0.1% (w/w) isomalathion, less than 0.2% (w/w) MeOOSPS, less than 0.1% (w/w) malaoxon, and less than 0.07% methyl malathion. 18. The pharmaceutical formulation of claim 17, wherein the malathion has a purity greater than 98.5% (w/w). 19. The pharmaceutical formulation of claim 18, wherein the malathion has a purity greater than 99.0% (w/w). 20. The pharmaceutical formulation of claim 17, wherein the malathion contains less than 0.1% (w/w) MeOOSPO, less than 0.1% (w/w) MeOSSPO, and less than 0.1% malathion carboxylic acids. 21. The pharmaceutical formulation of claim 17, comprising 0.65% (w/w) of the pharmaceutical grade malathion. 22. The pharmaceutical formulation of claim 17, further comprising terpineol, dipentene, pine needle oil, and isopropyl alcohol. 23. The pharmaceutical formulation of claim 22, wherein the pharmaceutical formulation comprises at least 70% (w/w) isopropyl alcohol. 24. The pharmaceutical formulation of claim 22, comprising at least 12% (w/w) terpineol, at least 10% (w/w) dipentene, and at least 0.28% (w/w) pine needle oil. 25. The pharmaceutical formulation of claim 17 wherein the formulation is a lotion, gel, cream or solution. 26. The pharmaceutical formulation of claim 17, wherein the amount of isomalathion is less than 0.05% (w/w), after storage for 3 months at 5.degree. C. 27. The pharmaceutical formulation of claim 17, wherein the amount of isomalathion is not more than 0.05% (w/w), after storage for 3 months at 25.degree. C. and 60% relative humidity. 28. The pharmaceutical formulation of claim 17, wherein the amount of isomalathion is not more than 0.05% (w/w), after storage for 3 months at 30.degree. C. and 60% relative humidity. 29. The pharmaceutical formulation of claim 17, wherein the amount of isomalathion is not more than 0.07% (w/w), after storage for 3 months at 40.degree. C. and 75% relative humidity. 30. A pharmaceutical formulation comprising pharmaceutical grade malathion, said pharmaceutical grade malathion having a purity greater than 98.5% and containing 0.1% or less (w/w) MeOOSPO, 0.1% or less (w/w) MeOSSPO, 0.2% or less (w/w) MeOOSPS, less than 0.1% (w/w) methyl malathion, 0.1% or less (w/w) malaoxon and 0.1% or less (w/w) isomalathion. 31. The pharmaceutical formulation of claim 30, wherein the malathion further contains less than 0.1% (w/w) malathion carboxylic acids. 32. The pharmaceutical formulation of claim 30, containing not more than about 0.1% (w/w) of any other detectable impurity. 33. The pharmaceutical formulation of claim 1, wherein the pharmaceutical formulation is a lotion. 34. The pharmaceutical formulation of claim 33, comprising pharmaceutical grade malathion having a purity of greater than 99% (w/w). 35. The pharmaceutical formulation of claim 33 wherein the malathion in the formulation contains 0.05% or less (w/w) MeOOSPO. 36. The pharmaceutical formulation of claim 33, comprising pharmaceutical grade malathion containing 0.1% or less (w/w) of any detectable impurity other than MeOOSPO, MeOSSPO, MeOOSPS, methyl malathion, malaoxon or isomalathion. 37. The pharmaceutical formulation of claim 33, wherein the malathion in the formulation contains 0.08% or less (w/w) methyl malathion. 38. The pharmaceutical formulation of claim 33, wherein the malathion in the formulation contains 0.05% or less (w/w) isomalathion. 39. The pharmaceutical formulation of claim 33, wherein the malathion in the formulation contains 0.2% or less (w/w) diethyl fumarate and 0.2% or less (w/w) dimethylmalathion. 40. The formulation of claim 33, wherein the malathion in the formulation contains less than 0.05% (w/w) malaoxon. 41. The pharmaceutical formulation of claim 33 wherein the malathion in the formulation contains 0.1% or less (w/w) MeOOSPS. 42. The pharmaceutical formulation of claim 33, wherein the amount of isomalathion is not more than 0.1% (w/w), after storage for 3 months at 25.degree. C. and 60% relative humidity. 43. The pharmaceutical formulation of claim 33, comprising 0.65% (w/w) of the pharmaceutical grade malathion. 44. The pharmaceutical formulation of claim 33, further comprising terpineol, dipentene, pine needle oil, and isopropyl alcohol. 45. The pharmaceutical formulation of claim 33, wherein the pharmaceutical formulation comprises at least 70% (w/w) isopropyl alcohol. 46. The pharmaceutical formulation of claim 33, comprising at least 12% (w/w) terpineol, at least 10% (w/w) dipentene, and at least 0.28% (w/w) pine needle oil. 47. The pharmaceutical formulation of claim 17, wherein the pharmaceutical formulation is a gel. 48. The pharmaceutical formulation of claim 47, wherein the malathion has a purity greater than 99.0% (w/w). 49. The pharmaceutical formulation of claim 47, wherein the malathion contains less than 0.1% (w/w) MeOOSPO, less than 0.1% (w/w) MeOSSPO, and less than 0.1% malathion carboxylic acids. 50. The pharmaceutical formulation of claim 47, comprising 0.65% (w/w) of the pharmaceutical grade malathion. 51. The pharmaceutical formulation of claim 47, further comprising terpineol, dipentene, pine needle oil, and isopropyl alcohol. 52. The pharmaceutical formulation of claim 47, wherein the pharmaceutical formulation comprises at least 70% (w/w) isopropyl alcohol. 53. The pharmaceutical formulation of claim 47, wherein the amount of isomalathion is not more than 0.05% (w/w), after storage for 3 months at 25.degree. C. and 60% relative humidity. 54. The pharmaceutical formulation of claim 30, wherein the pharmaceutical formulation is a lotion. 55. The pharmaceutical formulation of claim 30, wherein the pharmaceutical formulation is a gel.