Prostamide-containing intraocular implants and methods of use thereof

Abstract

Prostamide-containing intraocular implants that biodegrade in the eye and that are effective for reducing intraocular pressure in an eye for a sustained period. The implants generally contain a prostamide, such as bimatoprost, and at least three distinct biodegradable polymers selected from polylactide and poly(lactide-co-glycolide) polymers and are optimized for placement in and compatibility with the anterior chamber of the eye, particularly the anterior chamber angle. Methods for making and using the implants to reduce ocular hypertension and intraocular pressure in a patient are described.

1 .- 18 . (canceled) 
     
     
         19 . A method for reducing ocular pressure in an eye of a patient, the method comprising:
 injecting a biodegradable intraocular implant into an eye of a patient in need thereof, the biodegradable intraocular implant comprising a biodegradable polymer matrix, polyethylene glycol 3350, and bimatoprost, wherein the bimatoprost and polyethylene glycol 3350 are associated with the biodegradable polymer matrix; and   treating the eye after injecting of the biodegradable intraocular implant into the eye, wherein the biodegradable intraocular implant swells during the treating, and wherein the biodegradable intraocular implant reaches a maximum swell size by about 2 months and contracts in size after the about 2 months.   
     
     
         20 . The method of  claim 19 , wherein the biodegradable polymer matrix comprises:
 a) an ester end poly(D,L-lactide) having an inherent viscosity of 0.25-0.35 dl/g,   b) an acid end poly(D,L-lactide) having an inherent viscosity of 0.16-0.24 dl/g, and   c) an ester end poly(D,L-lactide-co-glycolide) having an inherent viscosity of 0.16-0.24 dl/g and a D,L-lactide to glycolide molar ratio of about 75:25;   wherein the bimatoprost comprises 18 to 22% of the biodegradable intraocular implant by weight, the ester end poly(D,L-lactide) comprises 18 to 22% of the biodegradable intraocular implant by weight, the acid end poly(D,L-lactide) comprises 13.5 to 16.5% of the biodegradable intraocular implant by weight, the ester end poly(D,L-lactide-co-glycolide) comprises 36 to 44% of the biodegradable intraocular implant by weight, and wherein the polyethylene glycol 3350 comprises 3.5 to 6.5% of the biodegradable intraocular implant by weight, wherein the inherent viscosity of each of the poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers is determined for a 0.1% solution of the polymer in chloroform at 25° C.   
     
     
         21 . The method of  claim 20 , wherein the bimatoprost comprises 20% of the biodegradable intraocular implant by weight, the ester end poly(D,L-lactide) comprises 20% of the biodegradable intraocular implant by weight, the acid end poly(D,L-lactide) comprises 15% of the biodegradable intraocular implant by weight, the ester end poly(D,L-lactide-co-glycolide) comprises 40% of the biodegradable intraocular implant by weight, and wherein the polyethylene glycol 3350 comprises 5% of the biodegradable intraocular implant by weight. 
     
     
         22 . The method of  claim 19 , wherein the maximum swell size of the biodegradable intraocular implant is no greater than 4 times an initial diameter of the biodegradable intraocular implant prior to injection into the eye. 
     
     
         23 . The method of  claim 19 , wherein the maximum swell size of the biodegradable intraocular implant is less than 3 times an initial diameter of the biodegradable intraocular implant prior to injection into the eye. 
     
     
         24 . The method of  claim 19 , wherein the maximum swell size of the biodegradable intraocular implant is no greater than 2 times an initial length of the biodegradable intraocular implant prior to injection into the eye. 
     
     
         25 . The method of  claim 19 , wherein the biodegradable intraocular implant is rod-shaped and is formed by a hot-melt extrusion process and wherein, prior to injection in the eye, the biodegradable intraocular implant is 150 μm to 300 μm in diameter or width, 0.50 mm to 2.5 mm in length, and 30 μg to 100 μg in total weight. 
     
     
         26 . The method of  claim 19 , wherein the biodegradable intraocular implant is effective for reducing intraocular pressure in an eye for the about 2 months or longer after injection into the eye. 
     
     
         27 . The method of  claim 19 , wherein the patient has one or more of elevated intraocular pressure, ocular hypertension, or glaucoma. 
     
     
         28 . The method of  claim 19 , wherein the biodegradable intraocular implant is placed into the eye using an intraocular delivery apparatus, the apparatus comprising an elongate housing and a cannula extending longitudinally from the housing, the cannula having a proximal end and a distal sharp end and having a lumen extending therethrough, the lumen having an inner diameter sufficient to receive the biodegradable intraocular implant and permit translation of the biodegradable intraocular implant through the lumen and into the eye of the patient. 
     
     
         29 . The method of  claim 19 , wherein treating the eye comprises releasing a therapeutically effective amount of the bimatoprost at a nearly linear or constant rate for at least the 2 months. 
     
     
         30 . The method of  claim 19 , wherein the biodegradable intraocular implant is injected into the anterior chamber of the eye. 
     
     
         31 . The method of  claim 30 , wherein the biodegradable intraocular implant does not contact the corneal endothelium after placement in the anterior chamber of the eye. 
     
     
         32 . The method of  claim 19 , wherein the biodegradable intraocular implant is injected into the posterior chamber of the eye. 
     
     
         33 . The method of  claim 32 , wherein the biodegradable intraocular implant is injected into a ciliary sulcus of the eye. 
     
     
         34 . A method for reducing ocular pressure in an eye of a patient, the method comprising:
 injecting a biodegradable intraocular implant into a posterior chamber of an eye of a patient in need thereof, the biodegradable intraocular implant comprising a biodegradable polymer matrix, polyethylene glycol 3350, and bimatoprost, wherein the bimatoprost and polyethylene glycol 3350 are associated with the biodegradable polymer matrix, which comprises:   a) an ester end poly(D,L-lactide) having an inherent viscosity of 0.25-0.35 dl/g,   b) an acid end poly(D,L-lactide) having an inherent viscosity of 0.16-0.24 dl/g, and   c) an ester end poly(D,L-lactide-co-glycolide) having an inherent viscosity of 0.16-0.24 dl/g and a D,L-lactide to glycolide molar ratio of about 75:25;   wherein the bimatoprost comprises 18 to 22% of the biodegradable intraocular implant by weight, the ester end poly(D,L-lactide) comprises 18 to 22% of the biodegradable intraocular implant by weight, the acid end poly(D,L-lactide) comprises 13.5 to 16.5% of the biodegradable intraocular implant by weight, the ester end poly(D,L-lactide-co-glycolide) comprises 36 to 44% of the biodegradable intraocular implant by weight, and wherein the polyethylene glycol 3350 comprises 3.5 to 6.5% of the biodegradable intraocular implant by weight, wherein the inherent viscosity of each of the poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers is determined for a 0.1% solution of the polymer in chloroform at 25° C.   
     
     
         35 . The method of  claim 34 , further comprising treating the eye after injecting of the biodegradable intraocular implant in the posterior chamber of the eye, wherein the biodegradable intraocular implant swells during the treating, and wherein the biodegradable intraocular implant reaches a maximum swell size by about 2 months and contracts in size after the about 2 months.