Pulmonary delivery in treating disorders of the central nervous system

Abstract

A method for treating a disorder of the central nervous system includes administering to the respiratory tract of a patient a drug which is delivered to the pulmonary system, for instance to the alveoli or the deep lung. The drug is administered at a dose which is at least about two-fold less than the dose required by oral administration. Particles that include the drug can be employed. Preferred particles have a tap density of less than about 0.4 g/cm 3 . In addition to the medicament, the particles can include other materials such as, for example, phospholipids, amino acids, combinations thereof and others.

1 - 16 . canceled.  
     
     
         17 . A method for treating a disorder of the central nervous system comprising administering to the respiratory tract of a patient in need of treatment a drug for treating said disorder, wherein the drug is administered in a dose that is at least about two times less than that required by oral administration and wherein delivery is to the pulmonary system.  
     
     
         18 . The method of  claim 17  wherein the dose is between about two times and about five times less than that required by oral administration.  
     
     
         19 . The method of  claim 17  wherein the dose is between about two times and about ten times less than that required by oral administration.  
     
     
         20 . The method of  claim 17  wherein delivery is to the alveoli region of the pulmonary system.  
     
     
         21 . The method of  claim 17  wherein administering is for rescue therapy.  
     
     
         22 . The method of  claim 17  wherein administering is during ongoing treatment.  
     
     
         23 . The method of  claim 17  wherein the disorder is Parkinson's disease.  
     
     
         24 . The method of  claim 17  wherein the patient in need of treatment is suffering from diseases selected from the group consisting of migraine, anxiety, psychosis, depression, bipolar disorder, obsessive compulsive disorder, convulsions, seizures, epilepsy, Alzheimer's, attention deficit hyperactivity disorder and migraines.  
     
     
         25 . The method of  claim 17  wherein the drug is present in dry powder particles.  
     
     
         26 . The method of  claim 25  wherein the drug is present in the dry powder particles in an amount of at least 20 weight percent.  
     
     
         27 . The method of  claim 25  wherein the drug is present in the dry powder particles in an amount of at least 40 weight percent.  
     
     
         28 . The method of  claim 25  wherein the drug is present in the dry powder particles in an amount of at least 50 weight percent.  
     
     
         29 . The method of  claim 25  wherein the particles have a tap density of less than about 0.4 g/cm 3 .  
     
     
         30 . The method of  claim 25  wherein the particles have a mass median aerodynamic diameter of less than about 5 microns.  
     
     
         31 . The method of  claim 25  wherein the particles have a mass median geometric diameter greater than about 5 microns.  
     
     
         32 . The method of  claim 25  wherein the particles have a mass median aerodynamic diameter of less than about 3 microns.  
     
     
         33 . The method of  claim 25  wherein the particles include a phospholipid.  
     
     
         34 . The method of  claim 25  wherein the particles include citrate and a multivalent salt.  
     
     
         35 . The method of  claim 25  wherein the particles include an amino acid.  
     
     
         36 . The method of  claim 35  wherein the amino acid is leucine.  
     
     
         37 . The method of  claim 25  wherein the particles are administered via a dry powder inhaler.  
     
     
         38 . The method of  claim 17  further comprising co-administering at least one additional agent.  
     
     
         39 . A method for treating Parkinson's disease comprising administering to the respiratory tract of a patient in need of treatment or rescue therapy a drug for treating Parkinson's disease wherein the drug is administered in a dose that is at least about two times less than that required by oral administration and wherein delivery is to the pulmonary system.  
     
     
         40 . The method of  claim 39  wherein the drug is levodopa.  
     
     
         41 . The method of  claim 39  wherein the dose is between about two times and about five times less than that required by oral administration.  
     
     
         42 . The method of  claim 39  wherein the dose is between about two times and about ten times less than that required by oral administration.  
     
     
         43 . The method of  claim 39  wherein delivery is to the alveoli region of the pulmonary system.  
     
     
         44 . The method of  claim 39  wherein administering is for rescue therapy.  
     
     
         45 . The method of  claim 39  wherein administering is during ongoing treatment.  
     
     
         46 . The method of  claim 39  wherein the drug is present in dry powder particles.  
     
     
         47 . The method of  claim 46  wherein the drug is present in the dry powder particles in an amount of at least 20 weight percent.  
     
     
         48 . The method of  claim 46  wherein the drug is present in the dry powder particles in an amount of at least 40 weight percent.  
     
     
         49 . The method of  claim 46  wherein the drug is present in the dry powder particles in an amount of at least 50 weight percent.  
     
     
         50 . The method of  claim 46  wherein the particles have a tap density of less than about 0.4 g/cm 3 .  
     
     
         51 . The method of  claim 46  wherein the particles have a mass median aerodynamic diameter of less than about 5 microns.  
     
     
         52 . The method of  claim 46  wherein the particles have a mass median geometric diameter greater than about 5 microns.  
     
     
         53 . The method of  claim 46  wherein the particles have a mass median aerodynamic diameter of less than about 3 microns.  
     
     
         54 . The method of  claim 46  wherein the particles include a phospholipid.  
     
     
         55 . The method of  claim 46  wherein the particles include citrate and a multivalent salt.  
     
     
         56 . The method of  claim 46  wherein the particles include an amino acid.  
     
     
         57 . The method of  claim 46  wherein the amino acid is leucine.  
     
     
         58 . The method of  claim 46  wherein the particles are administered via a dry powder inhaler.  
     
     
         59 . The method of  claim 58  wherein the dry powder inhaler is a single dose breath activated dry powder inhaler.  
     
     
         60 . The method of  claim 39  further comprising co-administering at least one additional agent.  
     
     
         61 . A method for treating a disorder of the central nervous system comprising administering to the respiratory tract of a patient in need of treatment a drug for treating said disorder, wherein the drug is administered in a dose that is at least about two times less than that required by administration routes other than intravenous and wherein delivery is to the pulmonary system.  
     
     
         62 . A method for treating a disorder of the central nervous system comprising administering to the respiratory tract of a patient in need of treatment or rescue therapy ketoprofen, wherein ketoprofen is administered in a dose that is at least about two times less than that required by oral administration and wherein delivery is to the pulmonary system.  
     
     
         63 . A method for treating a disorder of the central nervous system comprising administering to the respiratory tract of a patient in need of rescue therapy a benzodiazepine drug, wherein the benzodiazepine drug is administered in a dose that is at least about two times less than that required by oral administration and wherein delivery is to the pulmonary system.  
     
     
         64 . A method of treating a disorder of the central nervous system comprising: administering to the respiratory tract of a patient in need of rescue therapy particles comprising an effective amount of a benzodiazepine drug wherein the particles are delivered to the pulmonary system and the benzodiazepine drug is released in the blood stream of the patient and reaches its site of action within a time sufficiently short to provide said rescue therapy.  
     
     
         65 . The method of  claim 64  wherein the rescue therapy is for a panic attack.  
     
     
         66 . The method of  claim 64  wherein the benzodiazepine drug is present in the particles in an amount ranging from about 1 to about 90 weight percent.  
     
     
         67 . The method of  claim 64  wherein the particles have a tap density less than about 0.4 g/cm 3 .  
     
     
         68 . The method of  claim 64  wherein the particles have a volume median geometric diameter of between about 5 micrometers and about 30 micrometers.  
     
     
         69 . The method of  claim 64  wherein the particles have an aerodynamic diameter of between about 1 and about 5 microns.  
     
     
         70 . The method of  claim 69  wherein the particles have an aerodynamic diameter of between about 1 and about 3 microns.  
     
     
         71 . The method of  claim 69  wherein the particles have an aerodynamic diameter of between about 3 and about 5 microns.  
     
     
         72 . The method of  claim 64  wherein delivery to the pulmonary system includes delivery to the alveoli.  
     
     
         73 . The method of  claim 64  wherein the particles include a phospholipid.  
     
     
         74 . The method of  claim 73  wherein the phospholipid has a matrix transition temperature which is no higher than the patient's physiological temperature.  
     
     
         75 . The method of  claim 73  wherein the phospholipid is present in the particles in an amount ranging from about 10 to about 99 weight percent.  
     
     
         76 . The method of  claim 64  wherein the particles include a hydrophobic amino acid.  
     
     
         77 . The method of  claim 76  wherein the hydrophobic amino acid is present in the particles in an amount of a least 10% by weight.  
     
     
         78 . The method of  claim 64  wherein the particles include citrate.  
     
     
         79 . The method of  claim 78  wherein the particles further include calcium chloride.  
     
     
         80 . The method of  claim 64  wherein delivery to the pulmonary system is by means of a dry powder inhaler.  
     
     
         81 . The method of  claim 64  wherein delivery to the pulmonary system is by means of a metered dose inhaler.