Claims for Patent: 9,492,316

Summary for Patent: 9,492,316

Title:	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.
Inventor(s):	Ghebremeskel; Alazar N. (Irvine, CA), Robinson; Michael R. (Irvine, CA)
Assignee:	Allergan, Inc. (Irvine, CA)
Application Number:	14/529,526
Patent Claims:	1. A biodegradable intracameral implant for reducing intraocular pressure (IOP) in an eye, the implant comprising a biodegradable polymer matrix, polyethylene glycol 3350, and a prostamide as the active agent, wherein the prostamide 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 prostamide constitutes 18 to 22% of the implant by weight, the ester end poly(D,L-lactide) constitutes 18 to 22% of the implant by weight, the acid end poly(D,L-lactide) constitutes 13.5 to 16.5% of the implant by weight, the ester end poly(D,L-lactide-co-glycolide) constitutes 36 to 44% of the implant by weight, and wherein the polyethylene glycol 3350 constitutes 3.5 to 6.5% of the 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.degree. C. 2. A biodegradable intracameral implant according to claim 1, wherein the prostamide constitutes 20% of the implant by weight, the ester end poly(D,L-lactide) constitutes 20% of the implant by weight, the acid end poly(D,L-lactide) constitutes 15% of the implant by weight, the ester end poly(D,L- lactide-co-glycolide) constitutes 40% of the implant by weight, and wherein the polyethylene glycol 3350 constitutes 5% of the implant by weight. 3. The implant of claim 2, wherein the implant is rod-shaped and is formed by a hot-melt extrusion process and wherein the implant is 150 .mu.m to 300 .mu.m in diameter or width, 0.50 mm to 2.5 mm in length, and 30 .mu.g to 100 .mu.g in total weight. 4. The implant of claim 3, wherein the implant does not contact the corneal endothelium after placement in the anterior chamber of an eye. 5. The implant of claim 3, wherein the implant is effective for reducing intraocular pressure in an eye for 2 months or longer after placement in the eye. 6. The implant of claim 3, wherein the prostamide is a compound having the formula (I) ##STR00006## wherein the dashed bonds represent a single or double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical may be interrupted by one or more oxide radicals and substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups wherein said alkyl radical comprises from one to six carbon atoms; B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrocarbyl aryl and heteroaryl radicals having from four to ten carbon atoms wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms; X is --N(R.sup.4).sub.2 wherein R.sup.4 is independently selected from the group consisting of hydrogen and a lower alkyl radical having from one to six carbon atoms; Z is .dbd.O; one of R.sup.1 and R.sup.2 is .dbd.O, --OH or a --O(CO)R.sup.6 group, and the other one is --OH or --O(CO)R.sup.6, or R.sup.1 is .dbd.O and R.sup.2 is H, wherein R.sup.6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or --(CH.sub.2)mR.sup.7 wherein m is 0 or an integer of from 1 to 10, and R.sup.7 is cycloalkyl radical, having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical, as defined above. 7. The implant of claim 3, wherein the prostamide is bimatoprost. 8. A method for reducing ocular pressure in an eye of a mammal, the method comprising placing a biodegradable intracameral implant according to claim 1 in an eye of the mammal, whereby the implant provides a prostamide to the eye in an amount effective for reducing ocular pressure in the eye. 9. The method of claim 8, wherein the mammal is a human patient that has elevated intraocular pressure, ocular hypertension, or glaucoma. 10. The method of claim 9, wherein the implant is placed in the anterior chamber of an eye of the patient. 11. The method of claim 10, wherein the implant is effective for reducing intraocular pressure in the eye for at least two months after placement in the anterior chamber of the eye. 12. The method of claim 11, wherein the prostamide is bimatoprost. 13. The method of claim 12, wherein the implant is formed by an extrusion process and wherein the implant is 150 to 300 .mu.m in diameter or width, 0.50 to 2.5mm in length, and 30 to 100 .mu.g in total weight. 14. The method of claim 13, wherein the implant does not contact the corneal endothelium after placement in the anterior chamber of the eye. 15. The method of claim 13, wherein the implant is placed in the eye(s) 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 implant and permit translation of the implant through the lumen and into the eye of the patient. 16. An apparatus for delivering a biodegradable intracameral implant into the eye of a patient, the apparatus comprising an intracameral implant according to claim 1, an elongate housing and a cannula extending longitudinally from the housing, the cannula having a proximal end, a distal sharp end, and a lumen extending therethrough, the lumen having an inner diameter sufficient to receive the intraocular implant and permit translation of the implant through the lumen and into the eye of the patient. 17. The apparatus of claim 16, wherein the cannula is a 25 gauge, 26 gauge, 27gauge, 28 gauge, 29 gauge, or 30 gauge needle. 18. A method for making a biodegradable intracameral implant according to claim 1, the method comprising mixing the prostamide with the poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers and polyethylene glycol 3350, extruding the mixture to form a filament, followed by cutting the filament to length suitable for placement in the anterior chamber or vitreous body of an eye to thereby form an intraocular implant.