Claims for Patent: 8,409,606

Summary for Patent: 8,409,606

Title:	Drug delivery through hydrogel plugs
Abstract:	An embodiment is a medical prosthesis for blocking or reducing tear flow through a punctum or canaliculus of a human eye and delivering a drug to the eye that comprises a dehydrated covalently crosslinked synthetic hydrophilic polymer hydrogel with dimensions to pass through a puncta lacrimali, with the dehydrated hydrogel absorbing physiological water to swell to at least 1 mm in cross-sectional width and conformably fit a canaliculus, with the hydrogel comprising a therapeutic agent dispersed through the hydrogel for release to an eye, with the hydrogel having a water content of at least about 50% by weight or volume when allowed to fully hydrate in vitro in physiological saline.
Inventor(s):	Sawhney; Amarpreet S. (Lexington, MA), Jarrett; Peter (Sudbury, MA), Bassett; Michael (Natick, MA), Blizzard; Charles (Westwood, MA)
Assignee:	Incept, LLC (Bedford, MA)
Application Number:	12/704,692
Patent Claims:	1. A medical prosthesis for blocking or reducing tear flow through a punctum or canaliculus of a human eye and delivering a drug to the eye that comprises: a punctal plug comprising a dehydrated covalently crosslinked synthetic hydrophilic polymer hydrogel wherein the hydrogel precursors are first covalently cross-linked to form the hydrogel and then stretched in length and dried, with the plug having dimensions to pass through a puncta lacrimali, and with the dehydrated hydrogel absorbing physiological water to swell to at least 1 mm in cross-sectional width to expand the plug to conformably fit a canaliculus, with the hydrogel thereby directly contacting tissue of the canaliculus in the expanded state and having a proximal face in fluid communication with a tear film of the eye and with the punctal plug further comprising a therapeutic agent dispersed through the hydrogel for sustained release through the proximal face to the tear film of the eye in an effective amount over a period of at least about seven days, with the hydrogel having a water content of at least about 50% by weight or volume when allowed to fully hydrate in vitro in physiological saline and being free of polysaccharides. 2. The prosthesis of claim 1 wherein the dehydrated hydrogel swells to at least the 1 mm width within 10 minutes of placement in a canaliculus. 3. The prosthesis of claim 1 wherein the amount of stretching increases the length of the hydrogel by a factor of at least about 1.5. 4. The prosthesis of claim 1 further comprising a visualization agent that is present while the hydrogel is present and is in a concentration effective to provide visibility of the agent to a human without a machine-aid. 5. The prosthesis of claim 1 providing a sustained release of the therapeutic agent into the tear film to provide a concentration of the agent in the tear film of at least about 50 ng/mL for at least the seven days. 6. The prosthesis of claim 1 wherein the therapeutic agent is encapsulated within microspheres dispersed throughout the hydro gel, with the microspheres being a blend of a plurality of microsphere collections, with the collections having distinct material compositions and distinct drug release rate profiles. 7. The prosthesis of claim 6 wherein a diameter range of the microspheres is from about 20 to about 150 microns. 8. The prosthesis of claim 6 further comprising an additional amount of the therapeutic agent, with the additional amount being dispersed within the hydrogel without encapsulation in the microspheres, with the additional amount providing an initial burst of release of the additional amount of therapeutic agent, as measurable by a plot of cumulative release of the therapeutic agent over time, with the initial burst being between hydrogel is placed into a physiological solution in vitro and wherein therapeutic agent associated with the microspheres does not substantially contribute to the initial burst. 9. The prosthesis of claim 6, with the hydrogel and agent-loaded microspheres being spontaneously degradable by hydrolysis of covalent bonds in water. 10. The prosthesis of claim 1, consisting essentially of the hydrogel and microspheres containing the therapeutic agent. 11. The prosthesis of claim 8 wherein the therapeutic agent is substantially insoluble in aqueous solution. 12. The prosthesis of claim 8 wherein the therapeutic agent is substantially soluble in aqueous solution. 13. The prosthesis of claim 1 wherein the hydrogel is a reaction product of a first synthetic polymer that comprises a plurality of polymerizable groups that are polymerized by free radical initiation. 14. The prosthesis of claim 1 wherein the hydrogel is a reaction product of a first synthetic water soluble polymer comprising at least three first functional groups and a second synthetic water soluble polymer that comprises at least three second functional groups, with the first and second functional groups reacting with each other to form covalent bonds and thereby form the hydrogel as a synthetic crosslinked hydrogel. 15. The prosthesis of claim 14 wherein the first polymer comprises polyethylene glycol and the first functional groups are succinimides, and wherein the second functional groups are selected from the group consisting of amine and thiol. 16. The prosthesis of claim 1 wherein the therapeutic agent comprises a prostaglandin analogue that is released in vivo from the hydrogel as placed in a canaliculus in an amount effective to reduce elevated intraocular pressure in patients suffering from open angle glaucoma or ocular hypertension over a time of at least about four weeks. 17. The prosthesis of claim 1 wherein the therapeutic agent comprises moxifloxacin and the moxifloxacin is releasable in vivo from the hydrogel into a tear film of an eye as placed in a canaliculus in an amount effective to substantially reduce S. aureus or S. epidermidis at the eye over a time of at least about six days. 18. The prosthesis of claim 17 wherein the moxifloxacin is in a base form. 19. The prosthesis of claim 16 wherein the prostaglandin analogue comprises travoprost. 20. The prosthesis of claim 1, consisting of the hydrogel and the additional amount of and the therapeutic agent. 21. The prosthesis of claim 1, wherein, at the time of expansion, the plug has the proximal face and a distal face joined to each other by a side surface, wherein the side surface provides the hydrogel that contacts the tissue, and the side surface has an area at least twice an area of the proximal face. 22. The prosthesis of claim 4, wherein the visualization agent is present in microspheres, and/or microparticles and/or microdroplets entrapped within the hydrogel. 23. The prosthesis of claim 4, wherein the visualization agent is covalently bound to the hydrogel.