Implantable polymeric device for sustained release of dopamine agonist

Abstract

The present invention provides compositions, methods, and kits for treatment of Parkinson's disease and other conditions for which treatment with a dopamine agonist is therapeutically beneficial. The invention provides a biocompatible nonerodible polymeric device which releases dopamine agonist continuously with generally linear release kinetics for extended periods of time. Dopamine agonist is released through pores that open to the surface of the polymeric matrix in which it is encapsulated. The device may be administered subcutaneously to an individual in need of continuous treatment with dopamine agonist.

1 - 28 . (canceled) 
     
     
         29 : A method for administration of a dopamine agonist to a mammal in need thereof, the method comprising administering at least one implantable device subcutaneously,
 wherein each of said at least one implantable devices comprises a dopamine agonist encapsulated within a biocompatible, nonerodible polymeric matrix,   wherein said dopamine agonist is continuously released in vivo from each of said at least one implantable devices over a sustained period of time through pores that open to the surface of said matrix at a rate that results in a plasma level of at least about 0.01 ng/ml at steady state.   
     
     
         30 : A method according to  claim 29 , wherein said at least one implantable device comprises a multiplicity of individual implantable devices, and wherein the combination of said implantable devices continuously releases dopamine agonist in vivo over a sustained period of time at a rate that results in a plasma level of at least about 0.05 ng/ml at steady state. 
     
     
         31 : A method according to  claim 29 , wherein the polymeric matrix comprises ethylene vinyl acetate copolymer (EVA). 
     
     
         32 : A method according to  claim 31 , wherein said EVA comprises about 33% vinyl acetate. 
     
     
         33 : A method according to  claim 29 , wherein each of said at least one implantable devices comprises about 10 to about 85% dopamine agonist. 
     
     
         34 : A method according to  claim 29 , wherein said dopamine agonist is selected from the group consisting of apomorphine, lisuride, pergolide, bromocriptine, pramipexole, ropinerole, and rotigotine. 
     
     
         35 : A method according to  claim 34 , wherein said dopamine agonist is apomorphine. 
     
     
         36 : A method according to  claim 29 , wherein said mammal has Parkinson's disease. 
     
     
         37 : A method according to  claim 29 , wherein said mammal has toxin- or disease-induced parkinsonism. 
     
     
         38 : A method according to  claim 29 , wherein said mammal has a condition selected from the group consisting of erectile dysfunction and restless leg syndrome. 
     
     
         39 : A method according to  claim 29 , wherein the sustained period of time is at least about 3 months. 
     
     
         40 : A method according to  claim 29 , wherein each of said at least one implantable devices is produced by an extrusion process. 
     
     
         41 : A method according to  claim 40 , wherein each of said at least one implantable devices comprises dimensions of about 2 to about 3 mm in diameter and about 2 to about 3 cm in length. 
     
     
         42 : A method according to  claim 41 , wherein each of said at least one implantable devices releases at least about 0.1 mg of dopamine agonist per day in vitro. 
     
     
         43 : A method according to  claim 29 , wherein each of said at least one implantable devices is subcutaneously implanted at a site selected from the group consisting of the upper arm, the back, and the abdomen. 
     
     
         44 : A method according to  claim 29 , further comprising administration of an anti-inflammatory agent. 
     
     
         45 : A method according to  claim 44 , wherein said anti-inflammatory agent is encapsulated within said matrix in at least one of said at least one implantable devices. 
     
     
         46 : A method according to  claim 44 , wherein said anti-inflammatory agent is encapsulated within a biocompatible, nonerodible polymeric matrix that does not comprise said dopamine agonist, and wherein said method comprises administration of said polymeric matrix comprising said anti-inflammatory agent subcutaneously. 
     
     
         47 : A method according to  claim 44 , wherein said anti-inflammatory agent is administered via a route selected from the group consisting of local injection, systemic injection, subcutaneous injection, and oral administration. 
     
     
         48 : A method according to  claim 44 , wherein each of said at least one implantable devices further comprises an antioxidant. 
     
     
         49 - 56 . (canceled) 
     
     
         57 : The method according to  claim 34 , wherein said dopamine agonist is lisuride. 
     
     
         58 : The method according to  claim 44 , wherein said anti-inflammatory agent is a steroid. 
     
     
         59 : The method according to  claim 44 , wherein said anti-inflammatory agent is a nonsteroidal anti-inflammatory drug (“NSAID”). 
     
     
         60 : The method according to  claim 44 , wherein said anti-inflammatory agent is an antihistamine. 
     
     
         61 : The method according to  claim 29 , wherein each of said at least one implantable devices is washed. 
     
     
         62 : The method according to  claim 29 , wherein each of said at least one implantable devices is uncoated. 
     
     
         63 : The method according to  claim 29 , wherein the plasma level is about 0.01 ng/ml to about 10 ng/ml at steady state.