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 biodegradable intraocular implant comprising 20 wt % bimatoprost and a biodegradable polymer matrix selected from the group consisting of:
 (i) a biodegradable polymer matrix comprising:
 (a) about 15 wt % of a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 85:15 
 (b) about 35 wt % of a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of 0.16 dl/g to 0.24 dl/g 
 (c) about 15 wt % of a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of about 0.50 dl/g to about 0.70 dl/g; and 
 (d) about 15 wt of a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 50:50, an inherent viscosity of 0.16-0.24 dl/g; 
   (ii) a biodegradable polymer matrix comprising:
 (a) about 30 wt % a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 85:15, 
 (b) about 40 wt % a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of 0.16 dl/g to 0.24 dl/g, 
 (c) about 5 wt % a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 50:50, and 
 (d) about 5 wt % a poly(D,L-lactide-co-glycolide) having an acid end group and a D,L-lactide to glycolide ratio of about 50:50; 
   (iii) a biodegradable polymer matrix comprising:
 (a) about 20 wt % a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of 16 dl/g to 0.24 dl/g, 
 (b) about 50 wt % a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of about 0.50 dl/g to about 0.70 dl/g; 
 (c) about 5 wt % a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 50:50, and 
 (d) about 5 wt % a poly(D,L-lactide-co-glycolide) having an acid end group and a D,L-lactide to glycolide ratio of about 50:50; 
   (iv) a biodegradable polymer matrix comprising:
 (a) about 25 wt % a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of 0.16 dl/g to 0.24 dl/g, 
 (b) about 50 wt % a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of about 0.50 dl/g to about 0.70 dl/g; and 
 (c) about 5 wt % a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 50:50; and 
   (v) a biodegradable polymer matrix comprising:
 (a) about 30 wt % a poly(D,L-lactide-co-glycolide) having an ester end group, a D,L-lactide to glycolide ratio of about 75:25, and an inherent viscosity of 0.16 dl/g to 0.24 dl/g, 
 (b) about 20 wt % a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 50:50, and 
 (c) about 30 wt % a poly(D,L-lactide-co-glycolide) having an ester end group and a D,L-lactide to glycolide ratio of about 85:15; 
   wherein the inherent viscosity is measured for a 0.1% solution in chloroform at 25° C.   
     
     
         20 . A method of treating glaucoma, ocular hypertension, or intraocular pressure in a patient in need thereof, the method comprising intraoculary administering into the anterior chamber of the eye of the patient the biodegradable intraocular implant of  claim 19 . 
     
     
         21 . An apparatus for delivering a biodegradable intraocular implant into the eye of a patient, the apparatus comprising:
 (i) the biodegradable intraocular implant of  claim 19 ,   (ii) an elongate housing, and   (iii) a cannula extending longitudinally from the elongate housing, the cannula having a proximal end, a distal sharp end, and a lumen extending there through, the lumen having an inner diameter sufficient to receive the biodegradable intraocular implant and permit translation of the implant through the lumen and into the eye of the patient.   
     
     
         22 . A biodegradable intraocular implant comprising:
 (i) a prostamide;   (ii) a polyethylene glycol;   (iii) a poly(D,L-lactide) having an ester end group;   (iv) a poly(D,L-lactide) having an acid end group; and   (v) a poly(D,L-lactide-co-glycolide).   
     
     
         23 . The biodegradable intraocular implant of  claim 22 , comprising:
 (i) about 18 wt % to about 22 wt % of the prostamide;   (ii) about 3.5 wt % to about 6.5 wt % of the polyethylene glycol;   (iii) about 18 wt % to about 22 wt % of the poly(D,L-lactide) having an ester end group;   (iv) about 13.5 wt % to about 16.5 wt % of the poly(D,L-lactide) having an acid end group; and   (v) about 36 wt to about 44 wt % of the poly(D,L-lactide-co-glycolide).   
     
     
         24 . The biodegradable intraocular implant of  claim 22 , comprising:
 (i) about 20 wt % of the prostamide;   (ii) about 5 wt % of the polyethylene glycol;   (iii) about 20 wt % of the poly(D,L-lactide) having an ester end group;   (iv) about 15 wt % of the poly(D,L-lactide) having an acid end group; and   (v) about 40 wt % of the poly(D,L-lactide-co-glycolide).   
     
     
         25 . The biodegradable intraocular implant of  claim 22 , wherein the poly(D,L-lactide) having an ester end group has an inherent viscosity of about 0.25 dl/g to about 0.35 dl/g; and the poly(D,L-lactide) having an acid end group has an inherent viscosity of about 0.16 dl/g to about 0.24 dl/g; wherein the inherent viscosity is measured for a 0.1% solution in chloroform at 25° C. 
     
     
         26 . The biodegradable intraocular implant of  claim 22 , wherein the poly(D,L-lactide-co-glycolide) has an ester end group, a D,L-lactide to glycolide ratio of about 75:25 and an inherent viscosity of about 0.16 dl/g to about 0.24 dl/g; wherein the inherent viscosity is measured for a 0.1% solution in chloroform at 25° C. 
     
     
         27 . The biodegradable intraocular implant of  claim 22 , wherein the polyethylene glycol has an average molecular weight from about 3,000 g/ml to about 20,000 g/mol. 
     
     
         28 . The biodegradable intraocular implant of  claim 22 , wherein the prostamide is bimatoprost. 
     
     
         29 . The biodegradable intraocular implant of  claim 22 , comprising:
 (i) about 20 wt % of the prostamide;   (ii) about 5 wt % of the polyethylene glycol;   (iii) about 20 wt % of the poly(D,L-lactide) having an ester end group with an inherent viscosity of about 0.25 dl/g to about 0.35 dl/g, wherein the inherent viscosity is measured for a 0.1% solution in chloroform at 25° C.;   (iv) about 15 wt % of the poly(D,L-lactide) having an acid end group with an inherent viscosity of about 0.16 dl/g to about 0.24 dl/g, wherein the inherent viscosity is measured for a 0.1% solution in chloroform at 25° C.; and   (v) about 40 wt % of the poly(D,L-lactide-co-glycolide) has an ester end group, a D,L-lactide to glycolide ratio of about 75:25 and an inherent viscosity of about 0.16 dl/g to about 0.24 dl/g, wherein the inherent viscosity is measured for a 0.1% solution in chloroform at 25° C.   
     
     
         30 . The biodegradable intraocular implant of  claim 29 , wherein the polyethylene glycol has an average molecular weight from about 3,000 g/ml to about 20,000 g/mol. 
     
     
         31 . The biodegradable intraocular implant of  claim 29 , wherein the prostamide is bimatoprost. 
     
     
         32 . A method of treating glaucoma in a patient in need thereof, the method comprising intraoculary administering into the anterior chamber of the eye of the patient the biodegradable intraocular implant of  claim 22 . 
     
     
         33 . A method of treating glaucoma in a patient in need thereof, the method comprising intraoculary administering into the anterior chamber of the eye of the patient the biodegradable intraocular implant of  claim 29 . 
     
     
         34 . A method of treating glaucoma, ocular hypertension, or intraocular pressure in a patient in need thereof, the method comprising intraoculary administering into the anterior chamber of the eye of the patient the biodegradable intraocular implant of  claim 31 . 
     
     
         35 . An apparatus for delivering a biodegradable intraocular implant into the eye of a patient, the apparatus comprising:
 (i) the biodegradable intraocular implant of  claim 22 ,   (ii) an elongate housing, and   (iii) a cannula extending longitudinally from the elongate housing, the cannula having a proximal end, a distal sharp end, and a lumen extending there through, the lumen having an inner diameter sufficient to receive the biodegradable intraocular implant and permit translation of the implant through the lumen and into the eye of the patient.   
     
     
         36 . An apparatus for delivering a biodegradable intraocular implant into the eye of a patient, the apparatus comprising:
 (i) the biodegradable intraocular implant of  claim 31 ,   (ii) an elongate housing, and   (iii) a cannula extending longitudinally from the elongate housing, the cannula having a proximal end, a distal sharp end, and a lumen extending there through, the lumen having an inner diameter sufficient to receive the biodegradable intraocular implant and permit translation of the implant through the lumen and into the eye of the patient.   
     
     
         37 . A method of treating glaucoma, ocular hypertension, or intraocular pressure in a patient in need thereof, the method comprising intraoculary administering into the anterior chamber of the eye of the patient a biodegradable intraocular implant comprising a prostamide and at least three different biodegradable polymers selected from the group consisting of:
 (a) a poly(D,L-lactide) having an acid end group and an inherent viscosity of 0.160.24 dl/g, as measured for a 0.1% solution in chloroform at 25° C.;   (b) a poly(D,L-lactide) having an ester end group and an inherent viscosity of 0.250.35 dl/g, as measured for a 0.1% solution in chloroform at 25° C.;   (c) a poly(D,L-lactide-co-glycolide) having an acid end group, an inherent viscosity of 0.16-0.24 dl/g (as measured for a 0.1% solution in chloroform at 25° C.), and a D,L-lactide:glycolide molar ratio of about 50:50;   (d) a poly(D,L-lactide-co-glycolide) having an ester end group, an inherent viscosity of 0.16-0.24 dl/g (as measured for a 0.1% solution in chloroform at 25° C.), and a D,L-lactide:glycolide molar ratio of about 50:50;   (e) a poly(D,L-lactide-co-glycolide) having an ester end group, an inherent viscosity of 0.16-0.24 dl/g (as measured for a 0.1% solution in chloroform at 25° C.), and a D,L-lactide:glycolide molar ratio of about 75:25;   (f) a poly(D,L-lactide-co-glycolide) having an ester end group, an inherent viscosity of 0.50-0.70 dl/g (as measured for a 0.1% solution in chloroform at 25° C.), and a D,L-lactide:glycolide molar ratio of about 75:25; and   (g) a poly(D,L-lactide-co-glycolide) having an ester end group, an inherent viscosity of 1.3-1.7 dl/g (as measured for a 0.1% solution in chloroform at 25° C.), and a D,L-lactide:glycolide molar ratio of about 85:15.   
     
     
         38 . The method of  claim 37 , wherein the prostamide is bimatoprost.