Claims for Patent: 6,514,482

Summary for Patent: 6,514,482

Title:	Pulmonary delivery in treating disorders of the central nervous system
Abstract:	A method of pulmonary delivery of a medicament, for example a dopamine precursor or a dopamine agonist, which includes administering to the respiratory tract of a patient in need of rescue therapy particles comprising an effective amount of a medicament. The particles are delivered to the pulmonary system and are released into the blood stream and delivered to the medicament's site of action in a time sufficiently short to provide the rescue therapy. In addition to the medicament, the particles can include other materials such as, for example, phospholipids, amino acids, combinations thereof and others. Preferred particles have a tap density of less than about 0.4 g/cm.sup.3.
Inventor(s):	Bartus; Raymond T. (Sudbury, MA), Emerich; Dwaine F. (Cranston, RI)
Assignee:	Advanced Inhalation Research, Inc. (Cambridge, MA)
Application Number:	09/665,252
Patent Claims:	1. A method of providing rescue therapy in the treatment of Parkinson's disease comprising: administering to the respiratory tract of a patient in need of rescue therapy particles comprising an effective amount of a dopamine precursor, a dopamine agonist or any combination thereof, wherein the particles are delivered to the pulmonary system and the dopamine precursor, the dopamine agonist or the combination thereof is released in the blood stream of the patient and reaches the central nervous system to provide said rescue therapy. 2. The method of claim 1 wherein the particles comprise levodopa. 3. The method of claim 2 wherein the levodopa is present in the particles in an amount ranging from about 1 to about 90 weight percent. 4. The method of claim 2 wherein the particles further comprise carbidopa. 5. The method of claim 1 wherein the particles comprise apomorphine. 6. The method of claim 1 wherein the particles further comprise a material selected from the group consisting of a phospholipid or combination of phospholipids, an amino acid, a hydroxydicarboxylic acid, a hydroxytricarboxylic acid, a salt of any of said acids, a multivalent metal salt and any combination thereof. 7. The method of claim 6 wherein the particles comprise a phospholipid or combination of phospholipids. 8. The method of claim 7 wherein the phospholipid or combination of phospholipids is present in the particles in an amount ranging from about 10 weight percent to about 99 weight percent. 9. The method of claim 1 wherein the particles have a matrix transition temperature that is no higher than the patient's physiological temperature. 10. The method of claim 6 wherein the particles comprise a hydroxydicarboxylic acid, a hydroxytricarboxylic acid or a salt of any of said acids. 11. The method of claim 10 wherein the particles comprise citrate. 12. The method of claim 10 wherein the particles further comprise a multivalent metal salt. 13. The method of claim 12 wherein the multivalent metal salt is calcium chloride. 14. The method of claim 9 wherein the material is present in the particles in an amount of at least 10 weight percent. 15. The method of claim 1 wherein the particles have a tap density less than about 0.4 g/cm.sup.3. 16. The method of claim 15 the particles have a tap density less than about 0.1 g/cm.sup.3. 17. The method of claim 1 wherein the particles have a volume median geometric diameter of between about 5 micrometers and about 30 micrometers. 18. The method of claim 1 wherein the particles have an aerodynamic diameter of between about 1 and about 5 microns. 19. The method of claim 18 wherein the particles have an aerodynamic diameter of between about 1 and about 3 microns. 20. The method of claim 1 wherein delivery to the pulmonary system is by means of a dry powder inhaler. 21. The method of claim 1 wherein delivery to the pulmonary system is by means of a metered dose inhaler. 22. The method of claim 1 wherein the patient is suffering with late stage Parkinson's disease. 23. Particles suitable for delivery to the pulmonary system comprising a dopamine precursor, a dopamine agonist or any combination thereof and a material selected from the group consisting of a phospholipid or combination of phospholipids, an amino acid, a hydroxydicarboxylic acid, a hydroxytricarboxylic acid, a salt of any of said acids, a multivalent metal salt and any combination thereof. 24. The particles of claim 23 wherein the particles comprise levodopa. 25. The particles of claim 24 wherein the levodopa is present in the particles in an amount ranging from about 1 to about 90 weight percent. 26. The particles of claim 24 wherein the particles further comprise carbidopa. 27. The particles of claim 23 wherein the particles comprise apomorphine. 28. The particles of claim 23 wherein the particles comprise a phospholipid or combination of phospholipids. 29. The particles of claim 28 wherein the phospholipid or combination of phospholipids is present in the particles in an amount ranging from about 10 weight percent to about 99 weight percent. 30. The particles of claim 28 wherein the particles have a matrix transition temperature that is no higher than the patient's physiological temperature. 31. The particles of claim 23 wherein the particles comprise a hydroxydicarboxylic acid, a hydroxytricarboxylic acid, or any salt of said acids. 32. The particles of claim 31 wherein the particles comprise citrate. 33. The particles of claim 31 wherein the particles further comprise a multivalent metal salt. 34. The particles of claim 33 wherein the multivalent metal salt is calcium chloride. 35. The particles of claim 23 wherein the material is present in the particles in an amount of at least 10 weight percent. 36. The particles of claim 23 wherein the particles have a tap density less than about 0.4 g/cm.sup.3. 37. The particles of claim 36 wherein the particles have a tap density less than about 0.1 g/cm.sup.3. 38. The particles of claim 23 wherein the particles have a volume median geometric diameter of between about 5 micrometers and about 30 micrometers. 39. The particles of claim 23 wherein the particles have an aerodynamic diameter of between about 1 and about 5 microns. 40. The particles of claim 39 wherein the particles have an aerodynamic diameter of between about 1 and about 3 microns. 41. Particles suitable for delivery to the pulmonary system comprising: a dopamine precursor, a dopamine agonist or any combination thereof; a phospholipid or combination of phospholipids; and a material selected from the group consisting of an amino acid, a hydroxydicarboxylic acid, a hydroxytricarboxylic acid, a salt of any of said acids, a multivalent metal salt and any combination thereof. 42. Particles suitable for delivery to the pulmonary system comprising: a dopamine precursor, a dopamine agonist or any combination thereof; a saccharide; and a material selected from the group consisting of a phospholipid or combination of phospholipids, an amino acid, a hydroxydicarboxylic acid, a hydroxytricarboxylic acid, a salt of any of said acids, a multivalent metal salt and any combination thereof.