Sustained release delivery of active agents to treat glaucoma and ocular hypertension

Abstract

The methods described herein provide treatment of glaucoma, ocular hypertension, and elevated intraocular pressure with latanoprost or other therapeutic agent(s). Implant devices for insertion into a punctum of a patient provide sustained release of latanoprost or other therapeutic agent(s) that is maintained for 7, 14, 21, 30, 45, 60, or 90 days or more, thus avoiding patient noncompliance and reducing or lowering adverse events associated with eye drop administration of latanoprost or other therapeutic agent(s) and other therapeutic agent(s).

1 - 27 . (canceled) 
     
     
         28 . A method for reducing intraocular pressure in an eye of a patient having an elevated baseline intraocular pressure of 21 to 30 mmHg, comprising:
 administering to the patient a latanoprost sustained release topical formulation for at least four weeks wherein the intraocular pressure is reduced by at least about 10% from baseline at week 4,   wherein the latanoprost sustained release topical formulation continually releases latanoprost from a punctal implant to the eye of the patient, and   wherein the punctal implant comprises a first axis, defined by a proximal end of the implant, and a second axis, defined by the distal end of the implant, and at least an angled intersection between the first and second axis from about 45 degrees to about 135 degrees.   
     
     
         29 . The method of  claim 28 , wherein the punctal implant is configured to inhibit expulsion when implanted in a punctum of the eye. 
     
     
         30 . The method of  claim 28 , wherein the intraocular pressure is reduced an amount selected from the group consisting of at least 15% from baseline, at least 20% from baseline, and at least 25% from baseline. 
     
     
         31 . The method of  claim 28 , wherein the latanoprost is released for at least 8 weeks. 
     
     
         32 . The method of  claim 28 , wherein the latanoprost is released for at least 12 weeks. 
     
     
         33 . The method of  claim 28 , wherein the latanoprost sustained release topical formulation is contained within a drug insert disposed in the punctal implant, wherein the drug insert comprises a matrix and an impermeable sheath body. 
     
     
         34 . The method of  claim 33 , wherein the matrix comprises silicone. 
     
     
         35 . The method of  claim 33 , wherein the impermeable sheath body comprises polyimide. 
     
     
         36 . The method of  claim 28 , wherein the reduction in intraocular pressure is maintained for a continuous period of time selected from the group consisting of: up to about 28 days, up to about 56 days, up to about 84 days, and up to about 105 days. 
     
     
         37 . The method of  claim 28 , wherein the reduction in intraocular pressure is maintained for a continuous period of time selected from the group consisting of: up to about 4 weeks, up to about 8 weeks, and up to about 12 weeks. 
     
     
         38 . The method of  claim 28 , wherein the latanoprost sustained release formulation releases less than a therapeutic dose of latanoprost as compared to Xalatan on a daily basis. 
     
     
         39 . The method of  claim 28 , wherein latanoprost sustained release formulation releases less than an average 1.5 micrograms of latanoprost on a daily basis. 
     
     
         40 . The method of  claim 28 , wherein the latanoprost sustained release formulation comprises at least about 3.5 micrograms of latanoprost. 
     
     
         41 . The method of  claim 28 , wherein the punctal implant is inserted into an upper punctum of the eye. 
     
     
         42 . The method of  claim 28 , wherein the punctal implant is inserted into a lower punctum of the eye. 
     
     
         43 . The method of  claim 28 , wherein the punctal implant is inserted into an upper or lower punctum of one eye of the patient. 
     
     
         44 . The method of  claim 28 , wherein the punctal implant is inserted into an upper or lower punctum of both eyes of the patient. 
     
     
         45 . A method for reducing intraocular pressure in an eye of a patient having an elevated baseline intraocular pressure of 21 to 30 mmHg, comprising:
 administering to the patient a latanoprost sustained release topical formulation for at least four weeks wherein the intraocular pressure is reduced by at least 10% from baseline at week 4,   wherein the latanoprost sustained release topical formulation continually releases latanoprost from a punctal implant to the eye of the patient at an average daily rate less than a therapeutic dose of latanoprost as compared to Xalatan, and   wherein the punctal implant comprises a first axis, defined by a proximal end of the implant, and a second axis, defined by the distal end of the implant, and at least an angled intersection between the first and second axis from about 45 degrees to about 135 degrees.   
     
     
         46 . The method of  claim 45 , wherein the intraocular pressure is reduced an amount selected from the group consisting of at least 15% from baseline, at least 20% from baseline, and at least 25% from baseline. 
     
     
         47 . The method of  claim 45 , wherein the latanoprost is released for at least 8 weeks. 
     
     
         48 . The method of  claim 45 , wherein the latanoprost is released for at least 12 weeks. 
     
     
         49 . The method of  claim 45 , wherein the latanoprost sustained release topical formulation is contained within a drug insert disposed in the punctal implant, wherein the drug insert comprises a matrix and an impermeable sheath body. 
     
     
         50 . The method of  claim 49 , wherein the matrix comprises silicone. 
     
     
         51 . The method of  claim 49 , wherein the impermeable sheath body comprises polyimide. 
     
     
         52 . The method of  claim 45 , wherein latanoprost sustained release formulation releases less than an average 1.5 micrograms of latanoprost on a daily basis. 
     
     
         53 . The method of  claim 45 , wherein the punctal implant is inserted into an upper punctum of the eye. 
     
     
         54 . The method of  claim 45 , wherein the punctal implant is inserted into a lower punctum of the eye. 
     
     
         55 . A method for reducing intraocular pressure in an eye of a patient having an elevated baseline intraocular pressure of 21 to 30 mmHg, comprising:
 administering to the patient a latanoprost sustained release topical formulation for at least four weeks wherein the intraocular pressure is reduced by at least 10% from baseline at week 4,   wherein the latanoprost sustained release topical formulation continually releases latanoprost from a punctal implant to the eye of the patient at an average daily rate less than about 1.5 micrograms of latanoprost, and   wherein the punctal implant comprises a first axis, defined by a proximal end of the implant, and a second axis, defined by the distal end of the implant, and at least an angled intersection between the first and second axis from about 45 degrees to about 135 degrees.