Implants with controlled drug delivery features and methods of using same

Abstract

Disclosed herein are drug delivery devices and methods for the treatment of ocular disorders requiring targeted and controlled administration of a drug to an interior portion of the eye for reduction or prevention of symptoms of the disorder. The devices are capable of controlled release of one or more drugs and may also include structures which allow for treatment of increased intraocular pressure by permitting aqueous humor to flow out of the anterior chamber of the eye through the device.

What is claimed is: 
     
         1 . A drug delivery ocular implant comprising:
 an outer shell having a proximal end and a distal end, the outer shell being shaped to define an interior chamber;   a drug positioned within the interior chamber;   a drug release element configured to release the drug from the interior chamber, the drug release element comprising:
 a distal seal member that includes at least one opening; 
 a proximal seal member that includes at least one opening; and 
 a membrane compressed between the distal seal member and the proximal seal member; and 
   a retainer configured to retain the drug release element in place relative to the outer shell;   wherein the drug release element is configured such that the drug passes through the at least one opening in the distal seal member, through the compressed membrane, through the at least one opening in the proximal seal member, and out the proximal end of the outer shell.   
     
     
         2 . The ocular implant of  claim 1 , wherein the retainer comprises one or more tabs that are folded to engage the proximal seal member. 
     
     
         3 . The ocular implant of  claim 2 , wherein the one or more tabs are folded to engage the membrane. 
     
     
         4 . The ocular implant of  claim 1 , wherein the outer shell comprises one or more slots and wherein the retainer extends into the one or more slots and is positioned proximally of the proximal seal member. 
     
     
         5 . The ocular implant of  claim 1 , wherein the retainer has a lateral length that is greater than an inner diameter of the interior chamber adjacent the retainer and that is less than or equal to an outer diameter of the outer shell adjacent the retainer. 
     
     
         6 . The ocular implant of  claim 1 , wherein the interior chamber includes a shelf, and wherein the distal seal member is seated against the shelf. 
     
     
         7 . The ocular implant of  claim 1 , wherein the membrane comprises ethylene vinyl acetate having a concentration of vinyl acetate between about 10% and about 30%. 
     
     
         8 . The ocular implant of  claim 1 , wherein the compressed membrane has a thickness of between about 75 microns and about 125 microns. 
     
     
         9 . The ocular implant of  claim 1 , wherein the membrane is compressed from an uncompressed state by an amount between about 20 microns and about 40 microns. 
     
     
         10 . The ocular implant of  claim 1 , wherein the drug release element provides an elution rate between about 15 nanograms per day and about 35 nanograms per day. 
     
     
         11 . The ocular implant of  claim 1 , configured to hold a volume of the drug between about 40 nanoliters and about 150 nanoliters. 
     
     
         12 . The ocular implant of  claim 1 , wherein the ocular implant has a total longitudinal length of between about 1 mm and about 3 mm. 
     
     
         13 . The ocular implant of  claim 1 , wherein the outer shell comprises a ceramic material. 
     
     
         14 . The ocular implant of  claim 1 , further comprising at least one fluid inflow pathway and at least one fluid outflow pathway wherein the at least one fluid inflow pathway and the at least one fluid outflow pathway are configured to deliver ocular fluid to a physiological outflow pathway. 
     
     
         15 . The ocular implant of  claim 14 , wherein the outer shell includes an opening between the interior chamber and the inflow pathway, and wherein the ocular implant further comprises a seal configured to impede fluid communication between the interior chamber the fluid inflow pathway. 
     
     
         16 . The ocular implant of  claim 15 , wherein the seal comprises a recess on a proximal side, and wherein a portion of the drug is positioned inside the recess of the seal. 
     
     
         17 . The ocular implant of  claim 14 , further comprising a flange extending laterally outwardly between the at least one fluid inflow pathway and the at least one fluid outflow pathway. 
     
     
         18 . The ocular implant of  claim 14 , further comprising one or more standoffs configured to reduce compression of the physiological outflow pathway by the implant. 
     
     
         19 . The ocular implant of  claim 14 , wherein the physiological outflow pathway is Schlemm's Canal. 
     
     
         20 . The ocular implant of  claim 14 , further comprising a positioning protrusion configured to engage an implantation tool to facilitate rotation of the implant about a longitudinal axis during implantation. 
     
     
         21 . The ocular implant of  claim 1 , wherein the drug is formulated as an oil. 
     
     
         22 . The ocular implant of  claim 1 , wherein the drug comprises one or more of a prostaglandin, a prostaglandin analog, a prostaglandin inhibitor, and a beta-adrenergic receptor antagonist. 
     
     
         23 . The ocular implant of  claim 1 , further comprising one or more retention features configured to anchor the ocular implant in ocular tissue. 
     
     
         24 . The ocular implant of  claim 23 , wherein the one or more retention features includes a retention protrusion on the distal end of the outer shell, wherein the retention protrusion is configured to anchor the ocular implant at a target tissue site. 
     
     
         25 . The ocular implant of  claim 1 , wherein the ocular implant is configured to be positioned in the supraciliary space. 
     
     
         26 . The ocular implant of  claim 25 , wherein the ocular implant is configured to be positioned in the suprachoroidal space. 
     
     
         27 . The ocular implant of  claim 1 , wherein the ocular implant is configured to be positioned in the suprachoroidal space. 
     
     
         28 . The ocular implant of  claim 1 , wherein the outer shell is flexible. 
     
     
         29 . A method of making a drug delivery ocular implant, the method comprising:
 providing an outer shell having a proximal end and a distal end, the outer shell defining an interior chamber;   placing a drug into the interior chamber;   inserting a distal seal member into the interior chamber;   inserting a membrane into the interior chamber;   inserting a proximal seal member into the interior chamber;   pressing the proximal seal member towards the distal seal member to compress the membrane into a compressed state; and   attaching a retainer to retain the membrane in the compressed state.   
     
     
         30 . The method of  claim 29 , wherein the outer shell comprises one or more slots and wherein attaching the retainer comprises inserting the retainer laterally through the one or more slots such that the retainer is disposed proximally of the proximal seal member. 
     
     
         31 . The method of  claim 29 , wherein the retainer comprises one or more tabs, and wherein the method further comprises folding the tabs of the retainer to engage the proximal seal member. 
     
     
         32 . The method of  claim 29 , wherein the outer shell includes at least one fluid inflow pathway and at least one fluid outflow pathway wherein the at least one fluid inflow pathway and the at least one fluid outflow pathway are configured to deliver ocular fluid to a physiological outflow pathway, wherein the outer shell includes an opening between the interior chamber and the inflow pathway, and wherein the method further includes inserting a seal configured to impede fluid communication between the interior chamber the fluid inflow pathway. 
     
     
         33 . The method of  claim 29 , wherein the distal seal member, the membrane, and the proximal seal member are inserted together. 
     
     
         34 . The method of  claim 29 , wherein the outer shell includes one or more retention features configured to anchor the ocular implant in ocular tissue. 
     
     
         35 . A drug delivery ocular implant comprising:
 an outer shell having an interior chamber providing a drug reservoir;   a distal seal member;   a proximal seal member;   a membrane configured to be pressed between the distal seal member and the proximal seal member such that the membrane is in a compressed state, wherein the membrane in the compressed state is configured to be permeable to a drug such that the drug elutes through the membrane; and   a retainer configured to maintain the membrane in the compressed state.   
     
     
         36 . The ocular implant of  claim 35 , wherein the retainer comprises one or more tabs that are configured to fold to secure the retainer. 
     
     
         37 . The ocular implant of  claim 35 , wherein the outer shell comprises one or more slots and wherein the retainer is configured to extend into the one or more slots. 
     
     
         38 . The ocular implant of  claim 35 , wherein the membrane comprises ethylene vinyl acetate having a concentration of vinyl acetate between about 10% and about 30%, wherein the ocular implant is configured such that the membrane in the compressed state has a thickness of between about 75 microns and about 125 microns and such that the membrane is compressed from an uncompressed state by an amount between about 20 microns and about 40 microns. 
     
     
         39 . The ocular implant of  claim 35 , wherein the drug reservoir is configured to hold a volume of the drug between about 40 nanoliters and about 150 nanoliters. 
     
     
         40 . The ocular implant of  claim 35 , further comprising one or more retention features configured to anchor the ocular implant in ocular tissue. 
     
     
         41 . The ocular implant of  claim 35 , wherein the ocular implant is configured to be positioned in the supraciliary space. 
     
     
         42 . The ocular implant of  claim 41 , wherein the ocular implant is configured to be positioned in the suprachoroidal space. 
     
     
         43 . The ocular implant of  claim 35 , wherein the ocular implant is configured to be positioned in the suprachoroidal space.