Sustained release intraocular implants and methods for treating ocular neuropathies

Abstract

Biocompatible intraocular implants include a beta adrenergic receptor antagonist and a polymer associated with the beta adrenergic receptor antagonist to facilitate release of the beta adrenergic receptor antagonist into an eye for an extended period of time. The beta adrenergic receptor antagonist may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The implants may be placed in an eye to treat one or more ocular conditions, such as an ocular neuropathies, for example, various forms of glaucoma.

1 . A biodegradable drug delivery implant comprising: 
 a beta adrenergic receptor antagonist associated with a biodegradable polymer matrix that releases drug at a rate effective to sustain release of an amount of the beta adrenergic receptor antagonist from the implant for a time effective to reduce intraocular pressure in an eye in which the implant is placed, the time being at least about one week after the implant is placed in the eye.    
   
   
       2 . The implant of  claim 1 , wherein the beta adrenergic receptor antagonist is selected from the group consisting of timolol, betaxol, levobunolol, carteolol, metipranolol, derivatives thereof and mixtures thereof.  
   
   
       3 . The implant of  claim 1 , wherein the beta adrenergic receptor antagonist is a beta non-specific adrenergic antagonist.  
   
   
       4 . The implant of  claim 1 , wherein the beta adrenergic receptor antagonist is selected from the group consisting of timolol, salts thereof, and mixtures thereof.  
   
   
       5 . The implant of  claim 1 , wherein the beta adrenergic receptor antagonist is timolol maleate.  
   
   
       6 . The implant of  claim 1 , wherein the beta adrenergic receptor antagonist is dispersed within the biodegradable polymer matrix.  
   
   
       7 . The implant of  claim 1 , wherein the matrix comprises a mixture of a first biodegradable polymer, and a different second biodegradable polymer.  
   
   
       8 . The implant of  claim 1  wherein the beta adrenergic receptor antagonist is provided in an amount of up to about 50% by weight of the implant.  
   
   
       9 . The implant of  claim 1  wherein the beta adrenergic receptor antagonist is provided in an amount of up to about 30% by weight of the implant.  
   
   
       10 . The implant of  claim 1  wherein the beta adrenergic receptor antagonist is provided in an amount of about 10% by weight of the implant.  
   
   
       11 . The implant of  claim 1  wherein the beta adrenergic receptor antagonist is timolol maleate and is provided in an amount of about 26% by weight of the implant.  
   
   
       12 . The implant of  claim 1 , wherein the matrix releases drug at a rate effective to sustain release of an amount of the beta adrenergic receptor antagonist from the implant for at least about one week from the time the implant is placed in the eye.  
   
   
       13 . The implant of  claim 1 , wherein the matrix releases drug at a rate effective to sustain release of an amount of the beta adrenergic receptor antagonist from the implant for at least about one month from the time the implant is placed in the eye.  
   
   
       14 . The implant of  claim 1 , wherein the matrix releases drug at a rate effective to sustain release of an amount of the beta adrenergic receptor antagonist from the implant for at least about 3 months from the time the implant is placed in the eye.  
   
   
       15 . The implant of  claim 1 , wherein the beta adrenergic receptor antagonist is timolol and the matrix releases drug at a rate effective to sustain release of a therapeutically effective amount of timolol for about three months.  
   
   
       16 . The implant of  claim 1 , wherein the implant is structured to be placed in the anterior chamber of the eye.  
   
   
       17 . The implant of  claim 1 , wherein the beta adrenergic receptor antagonist is a timolol maleate provided in an amount of about 20% by weight of the implant, and the biodegradable polymer matrix comprises a combination of two different polylactide polymers.  
   
   
       18 . The implant of  claim 1  which is a filament in form.  
   
   
       19 . A method of reducing intraocular pressure in an eye of a patient, comprising the step of placing the implant of  claim 1  in an eye of the patient to provide a therapeutically effective amount of the beta adrenergic receptor antagonist to the patient for at least about one week.  
   
   
       20 . A method of reducing intraocular pressure in an eye of a patient, comprising the step of placing the implant of  claim 3  in an eye of the patient to provide a therapeutically effective amount of the beta adrenergic receptor antagonist to the patient for at least about one week.  
   
   
       21 . A method of reducing intraocular pressure in an eye of a patient, comprising the step of placing the implant of  claim 6  in an eye of the patient to provide a therapeutically effective amount of the beta adrenergic receptor antagonist to the patient for at least about one week.  
   
   
       22 . A method of reducing intraocular pressure in an eye of a patient, comprising the step of placing the implant of  claim 11  in an eye of the patient to provide a therapeutically effective amount of the beta adrenergic receptor antagonist to the patient for at least about one week.  
   
   
       23 . A method of making a biodegradable intraocular implant, comprising the step of: extruding a mixture of a beta adrenergic receptor antagonist and a biodegradable polymer component to form a biodegradable material that degrades at a rate effective to sustain release of an amount of the beta adrenergic receptor antagonist from the implant for a time effective to reduce ocular intraocular pressure in an eye in which the implant is placed, the time being at least about one week after the implant is placed in the eye.  
   
   
       24 . The method of  claim 23 , wherein the beta adrenergic receptor antagonist is selected from the group consisting of timolol, betaxol, levobunolol, carteolol, metipranolol, derivatives thereof and mixtures thereof.  
   
   
       25 . The method of  claim 23 , wherein the beta adrenergic receptor antagonist is selected from the group consisting of timolol, salts thereof, and mixtures thereof.  
   
   
       26 . The method of  claim 23 , wherein the polymer component comprises a mixture of different biodegradable polymers.  
   
   
       27 . The method of  claim 23 , wherein the implant is placed in the anterior chamber of the eye.  
   
   
       28 . The method of  claim 23 , wherein the implant is placed in the posterior segment of the eye.  
   
   
       29 . The method of  claim 23 , further comprising a step of administering a therapeutic agent in addition to the beta adrenergic receptor antagonist to the patient.  
   
   
       30 . A method of treating glaucoma, comprising the step of placing the implant of  claim 1  into an ocular region of a patient to provide a therapeutically effective amount of the beta adrenergic receptor antagonist to the eye of the patient for a period of at least one week, thereby treating the glaucoma.