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

Abstract

A method of decreasing intraocular pressure (IOP) in an eye of a patient in need thereof includes implanting a first lacrimal implant through a firsts punctum and into a first lacrimal canaliculus of the eye of the patient. The method may further comprise implanting a second lacrimal implant through a second punctum and into a second lacrimal canaliculus of the eye of the patient, and releasing, on a sustained basis a therapeutically effective amount of an intraocular pressure-reducing therapeutic agent.

1 - 114 . (canceled) 
     
     
         115 . A method for reducing intraocular pressure in an eye of a subject in need thereof, the method comprising:
 implanting a first lacrimal implant through a first punctum and into a first lacrimal canaliculus of the eye of the subject, the first lacrimal implant being configured to release a therapeutically effective amount of an intraocular pressure-reducing therapeutic agent to the eye of the patient on a sustained basis;   implanting a second lacrimal implant through a second punctum and into a second lacrimal canaliculus of the same eye of the subject, the second lacrimal implant being configured to release the intraocular pressure-reducing therapeutic agent to the eye of the patent on a sustained basis; and   releasing, on a sustained basis over a selected time course to the eye, a total amount of the intraocular pressure-reducing therapeutic agent from a combination of the first lacrimal implant and the second lacrimal implant, wherein said total amount is sufficient to reduce the intraocular pressure.   
     
     
         116 . The method according to  claim 115 , wherein the first implant is implanted through an upper punctum of the eye, and wherein the second implant is implanted through a lower punctum of the same eye. 
     
     
         117 . The method according to  claim 115 , wherein a member selected from the first implant and the second implant comprises from about 40 μg to about 115 μg of the therapeutic agent. 
     
     
         118 . The method according to  claim 115 , wherein the first or second implant each comprise about 46 μg or about 95 μg of the therapeutic agent. 
     
     
         119 . The method according to  claim 116 , wherein the second implant comprises about 95 μg of the therapeutic agent. 
     
     
         120 . The method according to  claim 118 , wherein the first and second implant comprise a total of about 141 μg of the therapeutic agent. 
     
     
         121 . The method according to  claim 115 , wherein the therapeutic agent is an anti-glaucoma drug selected from the group consisting of an adrenergic agonist, an adrenergic antagonist, a beta blocker, a carbonic anhydrase inhibitor, a parasympathomimetic, a prostaglandin analogue, a hypotensive lipid, a neuroprotectant, and combinations thereof. 
     
     
         122 . The method according to  claim 121 , wherein the therapeutic agent is a prostaglandin. 
     
     
         123 . The method according to  claim 121 , wherein the therapeutic agent is latanoprost. 
     
     
         124 . The method according to  claim 115 , wherein the sustained release of the therapeutic agent achieves a dosage of the therapeutic agent sufficient to reduce the intraocular pressure of the eye by at least 5 mm Hg from baseline for a continuous period of time of selected from at least 2 weeks, at least 3 weeks and at least 4 weeks after implantation of the first lacrimal implant and the second lacrimal implant. 
     
     
         125 . The method according to  claim 124 , wherein the eye has a baseline intraocular pressure of greater than about 21 mm Hg prior to said implanting the first lacrimal implant. 
     
     
         126 . The method according to  claim 124 , wherein the eye has a baseline intraocular pressure of between about 22 mm Hg and about 33 mm Hg prior to said implanting the first lacrimal implant. 
     
     
         127 . The method according to  claim 115 , wherein the implant comprises:
 a first member defining a first axis and having a first end along the first axis;   a second member defining a second axis and having a second end along the second axis, said second member defining a cavity configured for insertion of said therapeutic agent; and   a third member connecting the first end of the first member and the second end of the second member at a first angle to form an angled intersection, and the third member comprising a bore that is characterized by a third axis and a second angle,   wherein the first angle is defined by the first axis with respect to the second axis, the second angle is defined by the first axis with respective to the third axis, and the bore is configured to be accessible to an insertion tool for facilitating insertion of the implant.   
     
     
         128 . A method for reducing intraocular pressure in an eye of a subject in need thereof wherein both an upper punctum and a lower punctum of a same eye each have a lacrimal implant inserted into a lacrimal canaliculus and wherein the lacrimal implants are formulated to release, on a sustained basis, an intraocular pressure-reducing therapeutic agent, the method comprising:
 implanting a first lacrimal implant through a first punctum and into a first lacrimal canaliculus of the eye of the subject, the first lacrimal implant being configured to release a therapeutically effective amount of latanoprost, the intraocular pressure-reducing therapeutic agent, to the eye of the patient on a sustained basis;   implanting a second lacrimal implant through a second punctum and into a second lacrimal canaliculus of the same eye of the subject, the second lacrimal implant being configured to release a therapeutically effective amount of latanoprost to the eye of the patent on a sustained basis; and   releasing, on a sustained basis over about at least four weeks to the eye, a total amount of the intraocular pressure-reducing therapeutic agent from a combination of the first lacrimal implant and the second lacrimal implant, wherein said total amount is sufficient to reduce the intraocular pressure of the eye by at least 5 mm Hg from baseline for a continuous period of about 4 weeks.   
     
     
         129 . The method according to  claim 128 , wherein the first implant is implanted through an upper punctum of the eye, and wherein the second implant is implanted through a lower punctum of the same eye. 
     
     
         130 . The method according to  claim 129 , wherein the second implant comprises a higher concentration of latanoprost than the first implant. 
     
     
         131 . The method according to  claim 129 , wherein the first implant comprises about 46 μg of latanoprost. 
     
     
         132 . The method according to  claim 129 , wherein the second implant comprises about 95 μg of latanoprost. 
     
     
         133 . The method according to  claim 128 , wherein the first and second implant comprise a total of about 141 μg of the therapeutic agent. 
     
     
         134 . The method according to  claim 128 , wherein the eye has a baseline intraocular pressure of greater than about 21 mm Hg prior to said implanting the first lacrimal implant. 
     
     
         135 . The method according to  claim 128 , wherein the eye has a baseline intraocular pressure of between about 22 mm Hg and about 33 mm Hg prior to said implanting the first lacrimal implant.