Implantable therapeutic device
A therapeutic device to release a therapeutic agent comprises a porous structure coupled to a container comprising a reservoir. The reservoir comprises a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in the patient. The porous structure may comprise a first side coupled to the reservoir and a second side to couple to the patient to release the therapeutic agent. The length of the channels extending from the first side to the second side may comprise an effective length greater than a distance across the porous structure from the first side to the second side. The therapeutic device may comprise a penetrable barrier to inject therapeutic agent into the device when implanted in the patient.
1. An ophthalmic drug delivery system comprising:
a formulation comprising a therapeutic agent that is an inhibitor of complement factor D, the therapeutic agent having a concentration in a solution volume;
an extended release device configured to be implanted in an eye, the device comprising:
a refillable or flushable reservoir formed of a non-permeable material defining a hollow reservoir volume sized to receive the solution volume and defining at least one exit port, wherein the reservoir is configured to adopt an expanded profile configuration after insertion in the eye and introduction of the solution volume into the reservoir and configured to adopt a narrow profile configuration for removal from the eye;
a penetrable barrier positioned in an access port near a proximal end region of the device; and
a rigid porous structure coupled to the at least one exit port of the reservoir and formed of a porous material through which the therapeutic agent passively diffuses into the vitreous of the eye, wherein the rigid porous structure has a release rate, and a porosity P; and
an injector configured to penetrate the penetrable barrier while the device is implanted in the eye to refill or flush the reservoir through the penetrable barrier of the access port with an amount of the formulation, the injector comprising:
a needle having a first lumen and a second lumen;
an injection chamber configured to be in one-way fluid communication with the reservoir via the first lumen; and
a vent chamber configured to be in one-way fluid communication with the reservoir via the second lumen, wherein the vent chamber comprises a resistance to flow substantially lower than a resistance to flow through the rigid porous structure.
2. The system of claim 1 , wherein the inhibitor of complement factor D is FCFD4514S.
3. The system of claim 1 , wherein the drug formulation is a commercially available drug formulation of a complement factor D inhibitor.
4. The system of claim 1 , wherein the porous material comprises grains of a sintered material.
5. The system of claim 4 , wherein the sintered material is selected from the group consisting of metal, ceramic, glass and polymer.
6. The system of claim 4 , wherein the porous structure comprises a first side having a first plurality of openings and a second, opposite side having a second plurality of openings, wherein a void space is formed by a plurality of channels extending within the porous material between each of the first plurality of openings on the first side and each of the second plurality of openings on the second side.
7. The system of claim 6 , wherein the plurality of channels extending within the porous material extend around the grains of sintered material.
8. The system of claim 1 , wherein the at least one exit port has a defined diameter and is located near a distal end region of the device, and wherein the porous structure is positioned on or placed within the at least one exit port.
9. The system of claim 1 , wherein the non-permeable material extends distally around the porous material so as to define an opening to couple the porous material to the vitreous humor when the delivery system is implanted in the eye.
10. The system of claim 1 , wherein the access port comprises an opening formed in a retention structure supporting the penetrable barrier.
11. The system of claim 1 , wherein the injector is further configured to remove pre-existing fluid from the reservoir through the second lumen into the vent chamber.
12. The system of claim 11 , wherein the injector further comprises a valve having an open configuration and a closed configuration, wherein when the valve is in the open configuration a first amount of the formulation passes from the injection chamber through the first lumen and is retained in the reservoir, and wherein when the valve is in the closed configuration a second amount of the formulation passes from the injection chamber through the first lumen and is passed through the rigid porous structure into the vitreous of the eye.
13. The system of claim 12 , wherein the valve comprises a piston movable within the injection chamber and a moving component coupled to the piston configured to cover an opening extending between the injection chamber and the vent chamber upon advancement of the piston within the injection chamber.
14. The system of claim 13 , wherein the opening is covered by the moving component when the valve is in the closed configuration.
15. The system of claim 1 , wherein when in the expanded profile configuration the extended release device is positioned away from the visual path and avoids inhibiting vision.
16. The system of claim 15 , wherein the reservoir has a substantially constant volume in the expanded profile configuration.
17. The system of claim 15 , wherein the reservoir volume is within a range from about 50 uL to about 100 uL and no more than 200 uL so as not substantially increase intraocular pressure when the reservoir is in the expanded profile configuration.