Pulmonary delivery for levodopa

Abstract

In one aspect, the invention is related to a method of treating a patient with Parkinson's disease, the method including administering to the respiratory tract of the patient particles that include more than about 90 weight percent (wt %) of levodopa. The particles are delivered to the patient's pulmonary system, preferably to the alveoli or the deep lung.

1. A method of treating a patient with Parkinson's disease, that comprises:
 administering to the respiratory tract of the patient particles that include about 90 weight percent or more levodopa, and a salt wherein the formulation contains less than 10% by weight of a salt, and a non-reducing sugar, 
 
       wherein the particles are delivered to the pulmonary system. 
     
     
       2. A method of treating a patient with Parkinson's disease, that comprises:
 administering to the respiratory tract of the patient particles that consist essentially of about 90 weight percent or more levodopa, a non-reducing sugar and a salt wherein the formulation contains less than 10% by weight of the salt, 
 
       wherein the particles are delivered to the pulmonary system and have a tap density about 0.4 g/cm 3  or less, a volume median geometric diameter about 5 micrometers or more, and an aerodynamic diameter of from about 1 micrometer to about 5 micrometers. 
     
     
       3. The method of  claim 2 , wherein the particles have an aerodynamic diameter of from about 1 micrometer to about 3 micrometers. 
     
     
       4. The method of  claim 2 , wherein the particles have an aerodynamic diameter of from about 3 micrometer to about 5 micrometers. 
     
     
       5. The method of  claim 2 , wherein the particles gave a tap density about 0.3 g/cm 3  or less. 
     
     
       6. The method of  claim 2 , wherein the particles gave a tap density about 0.2 g/cm 3  or less. 
     
     
       7. The method of  claim 2 , wherein the particles gave a tap density about 0.1 g/cm 3  or less. 
     
     
       8. A method of treating a patient with Parkinson's disease, that comprises:
 administering to the respiratory tract of the patient particles that include about 90 weight percent or more levodopa, NaCl in an amount less than 10% by weight of NaCl, and a non-reducing sugar, 
 
       wherein the particles are delivered to the pulmonary system. 
     
     
       9. The method of  claim 8 , wherein the non-reducing sugar is trehalose. 
     
     
       10. A method of delivering an effective amount of L-Dopa to the pulmonary system, comprising:
 providing a mass of particles that include, by weight, about 90 percent or more L-Dopa, about 10 percent or less trehalose, and sodium chloride wherein the formulation contains about 3 percent or less sodium chloride; and administering via simultaneous dispersion and inhalation the particles, from a receptacle having the mass of the particles, to a human subject's respiratory tract. 
 
     
     
       11. A method of treating Parkinson's disease in a patient in need thereof comprising:
 administering to the respiratory tract of the patient, particles comprising sodium chloride and about 90% by weight or more of levodopa; and administering carbidopa to the patient.   
     
     
       12. The method of claim 11, wherein the particles further comprise a phospholipid. 
     
     
       13. The method of claim 11, wherein the particles further comprise dipalmitoyl phosphatidylcholine (DPPC). 
     
     
       14. The method of claim 11, wherein the particles comprise about 90% by weight of levodopa, about 8% by weight of DPPC and about 2% by weight of sodium chloride. 
     
     
       15. The method of claim 11, wherein the carbidopa is administered by injection or by oral administration. 
     
     
       16. The method of claim 11, wherein the carbidopa is administered orally. 
     
     
       17. The method of claim 11, further comprising oral administration of levodopa. 
     
     
       18. The method of claim 11, wherein carbidopa is administered orally in combination with oral administration of levodopa. 
     
     
       19. The method of claim 11, wherein the particles are delivered to the pulmonary system. 
     
     
       20. The method of claim 11, wherein the particles have a tap density of about 0.4 g/cm 3  or less, a volume median geometric diameter of about 5 microns or more and a aerodynamic diameter of from about 1 micron to about 5 microns. 
     
     
       21. The method of claim 11, wherein said carbidopa is administered before said levodopa. 
     
     
       22. The method of claim 11, wherein said carbidopa is administered after said levodopa. 
     
     
       23. The method of claim 11, wherein said carbidopa is administered at the same time as said levodopa. 
     
     
       24. A method of treating Parkinson's disease in a patient in need thereof comprising:
 administering to the respiratory tract of the patient, particles comprising levodopa, sodium chloride and dipalmitoyl phosphatidylcholine wherein the ratio of levodopa:dipalmitoyl phosphatidylcholine:sodium chloride is about 90:8:2; and administering carbidopa to the patient.