Compositions and Methods for Treatment of Symptoms in Parkinson's Disease Patients

Abstract

The invention provides dosage forms and methods utilizing nicotine to treat symptoms of a neurologic disorder. In some embodiments, the invention provides compositions for treatment of gait and balance problems associated with Parkinson's Disease.

1 . A pulsatile release dosage form for twice-daily administration, said form comprising a capsule or tablet comprising an effective amount of nicotine for treatment of symptoms of Parkinson's Disease or symptoms associated with dopaminergic treatment of Parkinson's Disease, wherein said capsule or tablet exhibits pulsatile release of said nicotine, and wherein nicotine is present at less than about 10 mg. 
     
     
         2 . The dosage form according to  claim 1 , wherein said pulsatile release comprises a first and second release peak, wherein said first release peak occurs within about two hours of administration to a patient, and said second release peak occurs between about two and about twelve hours of administration to a patient. 
     
     
         3 . The dosage form according to  claim 2 , wherein said dosage form is a capsule. 
     
     
         4 . The dosage form according to  claim 3 , wherein said capsule comprises a powder comprising nicotine for providing said first release peak upon administration to a patient, and said capsule further comprises beads comprising nicotine for providing said second release peak upon administration to a patient. 
     
     
         5 . The dosage form according to  claim 4 , wherein said beads are selected from the group consisting of enteric-coated beads, erodible-matrix beads, wax-coated beads, ethylcellulose-coated beads, silicone elastomer coated beads, and combinations thereof. 
     
     
         6 . The dosage form according to  claim 3 , wherein said capsule comprises a water-swellable polymeric membrane. 
     
     
         7 . The dosage form according to  claim 6 , wherein said water-swellable polymeric membrane ruptures following administration to a patient. 
     
     
         8 . The dosage form according to  claim 2 , wherein said dosage form is a tablet. 
     
     
         9 . The dosage form according to  claim 8 , wherein said tablet comprises a coating and a core, wherein said coating comprises nicotine for the first release peak, and said core comprises nicotine for the second release peak. 
     
     
         10 . The dosage form according to  claim 9 , wherein said coating is selected from an enteric coating, an erodible-matrix coating, a wax coating, an ethylcellulose coating, a silicone elastomer coating, and combinations thereof. 
     
     
         11 . (canceled) 
     
     
         12 . The dosage form according to  claim 1 , wherein said symptoms of Parkinson's Disease are gait and balance problems. 
     
     
         13 . The dosage form according to  claim 1 , wherein said symptoms associated with dopaminergic treatment of Parkinson's Disease are levodopa-induced dyskinesias. 
     
     
         14 . (canceled) 
     
     
         15 . The dosage form according to  claim 1 , wherein nicotine is present at about 6 mg. 
     
     
         16 . The dosage form according to  claim 14   claim 1 , wherein nicotine is present at about 4 mg. 
     
     
         17 . The dosage form according to  claim 1 , wherein nicotine is present at about 3 mg. 
     
     
         18 . The dosage form according to  claim 1 , wherein about 1-2 mg nicotine is released in a first release, and about 2-3 mg nicotine is released in a second release. 
     
     
         19 . The dosage form of  claim 18 , wherein said dosage form is capable of being administered so that one or more metabolites of said nicotine achieves a plasma level of about 1 to about 500 ng/ml within four hours of administration. 
     
     
         20 . The dosage form according to  claim 1 , wherein said dosage form further comprises levodopa, carbidopa, or a combination thereof. 
     
     
         21 . An extended release dosage form for once-daily administration, said form comprising a capsule or tablet comprising an effective amount of nicotine for treatment of symptoms of Parkinson's Disease or symptoms associated with dopaminergic treatment of Parkinson's Disease, wherein said capsule or tablet achieves an efficacious plasma concentration of nicotine or a metabolite thereof within one hour from administration for a duration of at least six hours and further wherein said capsule or tablet achieves a peak plasma concentration of nicotine or a metabolite thereof at least about two hours after administration, wherein nicotine is present at less than about 10 mg. 
     
     
         22 . The dosage form according to  claim 21 , wherein said extended release comprises a single peak plasma concentration of nicotine or a metabolite thereof, wherein said single peak plasma concentration occurs between about two hours and about 12 hours after administration. 
     
     
         23 . The dosage form according to  claim 22 , wherein said extended release comprises a single peak plasma concentration of nicotine or a metabolite thereof, wherein said single peak plasma concentration occurs between about six hours and about eight hours after administration. 
     
     
         24 . The dosage form according to  claim 21 , wherein said extended release achieves an efficacious plasma concentration of nicotine or a metabolite thereof within one hour from administration and achieves a duration of an efficacious plasma concentration of nicotine or a metabolite thereof for a period between about six to about 18 hours from administration. 
     
     
         25 . The dosage form according to  claim 24 , wherein said extended release achieves an efficacious plasma concentration of nicotine or a metabolite thereof within one hour from administration and achieves a duration of an efficacious plasma concentration of nicotine or a metabolite thereof for a period between about eight hours to about 14 hours from administration. 
     
     
         26 . The dosage form according to  claim 25 , wherein said extended release achieves an efficacious plasma concentration of nicotine or a metabolite thereof within one hour from administration and achieves a duration of an efficacious plasma concentration of nicotine or a metabolite thereof for a period between about ten hours to about 12 hours from administration. 
     
     
         27 . The dosage form according to  claim 21 , wherein said dosage form is a capsule. 
     
     
         28 . The dosage form according to  claim 21 , wherein said dosage form is a tablet. 
     
     
         29 . The dosage form according to  claim 21 , wherein said capsule or tablet comprises a water-swellable polymeric matrix. 
     
     
         30 . The dosage form according to  claim 21 , wherein said capsule or tablet comprises a matrix comprising at least one swellable hydrophilic polymer that swells with water to increase its size to promote gastric retention of the dosage form in the stomach. 
     
     
         31 . The dosage form according to  claim 21 , wherein said tablet comprises a coating and a core, wherein said coating is selected from an enteric coating, an erodible-matrix coating, a wax coating, an ethylcellulose coating, a silicone elastomer coating, and combinations thereof. 
     
     
         32 . The dosage form according to  claim 21 , said form comprising a liquid filled capsule comprising an effective amount of nicotine for treatment of symptoms of Parkinson's Disease or symptoms associated with dopaminergic treatment of Parkinson's Disease, wherein said capsule comprises a hard gelatin outer surface. 
     
     
         33 . The dosage form according to  claim 21 , wherein said symptoms of Parkinson's Disease are gait and balance problems. 
     
     
         34 . The dosage form according to  claim 21 , wherein said symptoms associated with dopaminergic treatment of Parkinson's Disease are levodopa-induced dyskinesias. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . The dosage form of  claim 21 , wherein said dosage form is capable of being administered so that one or more metabolites of said nicotine achieves a plasma level of about 1 to about 500 ng/ml within one hour of administration. 
     
     
         40 . The dosage form according to  claim 21 , wherein said dosage form further comprises levodopa, carbidopa, or a combination thereof. 
     
     
         41 . A method of treating gait and balance problems in a subject, comprising administering an oral composition comprising nicotine, wherein the gait and balance problems are direct symptoms of Parkinson's Disease. 
     
     
         42 . The method of  claim 41 , wherein the nicotine is administered in a dose of less than about 10 mg. 
     
     
         43 . The method of  claim 41 , wherein the nicotine is administered in a dose of about 6 mg. 
     
     
         44 . The method of  claim 41 , wherein the nicotine is administered in a dose of about 4 mg. 
     
     
         45 . The method of  claim 41 , wherein the nicotine is administered in a dose of about 3 mg. 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 41 , wherein said oral composition is capable of being administered so that nicotine or one or more metabolites of nicotine achieves a plasma level of about 1 to about 500 ng/ml within four hours of administration. 
     
     
         48 . The method of  claim 41 , wherein nicotine or one or more metabolites of nicotine achieves an efficacious plasma level within about one hour of administration and further achieves a maximum plasma level peak from two to twelve hours from administration. 
     
     
         49 . The method of  claim 41 , wherein said subject is not receiving a dopaminergic agent for treatment of Parkinson's Disease. 
     
     
         50 . The method of  claim 41 , wherein said subject is not receiving levodopa and/or carbidopa for treatment of Parkinson's Disease.