Drug delivery through hydrogel plugs

• US 8,563,027 B2
• Filed: 02/26/2013
• Issued: 10/22/2013
• Est. Priority Date: 02/12/2009
• Status: Active Grant

• Current Assignee: Incept LLC
• Original Assignee: Incept LLC
• Inventors: Jarrett, Peter, Bassett, Michael, Blizzard, Charles D., Sawhney, Amarpreet S.
• Primary Examiner(s): BASQUILL, SEAN M
• Application Number:
  US13/777,103
• Publication Number:
  US 20130172268A1
• Time in Patent Office: 238 Days
• Field of Search: 424/427, 514/530, 514/300, 264/118
• US Class Current: 424/427
• CPC Class Codes: A61B 17/12099 characterised by the location of the occluder
• CPC Class Codes: A61B 17/12159 Solid plugs; being solid before insertion
• CPC Class Codes: A61B 17/1219 expandable in contact with liquids
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 9/00772 Apparatus for restoration of tear ducts
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 31/04 Antibacterial agents

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.

Claims

1. A process for making a punctal plug for blocking or reducing tear flow through a punctum or canaliculus of an eye and delivering a drug to the eye comprising:

forming a covalently crosslinked hydrogel that is free of polysaccharides, the forming comprising reacting, in a presence of a drug, a first synthetic water soluble polymer precursor that comprises first functional groups and a second synthetic water soluble precursor that comprises second functional groups, with the first and second functional groups reacting with each other to form covalent crosslinking bonds, wherein the drug is dispersed within the hydrogel,

with the covalently crosslinked hydrogel being stretched in length and prepared in a dehydrated form,

with the dehydrated hydrogel absorbing physiological water to swell and directly contact a tissue of the canaliculus in an expanded state and having a proximal face in fluid communication with a tear film of the 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.

2. The process of claim 1, further comprising placing a visualization agent into the hydrogel at a concentration effective to provide visibility of the punctal plug to a human without a machine-aid.

3. The process of claim 2, wherein the visualization agent is present in microspheres, and/or microparticles and/or microdroplets entrapped within the hydrogel.

4. The process of claim 2, wherein the visualization agent is covalently bound to the hydrogel.

5. The process of claim 1, wherein, at the time of expansion, the punctal 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.

6. The process of claim 1, wherein the hydrogel spontaneously degrades by chemical hydrolysis in water.

7. The process of claim 1, wherein the hydrogel is covalently crosslinked with a third precursor that forms covalent bonds with the first functional group and the second functional group.

8. The process of claim 1, wherein the first synthetic polymer hydrogel precursor further comprises at least three of the first functional groups and the second synthetic water soluble precursor comprises at least three of the second functional groups.

9. The process of claim 1, wherein the hydrogel is a reaction product of a first synthetic polymer that 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.

10. The process of claim 1, wherein the prosthesis consists of

the hydrogel, the drug, and an agent that is selected from the group consisting of an imaging agent and a visualization agent.

11. The process of claim 1, wherein the drug is chosen from the group consisting of latanoprost, travoprost and moxifloxacin.

12. The process of claim 1, wherein the drug comprises a prostaglandin analogue.

13. The process of claim 1, wherein the drug is free of encapsulating materials.

14. The process of claim 1, wherein at least some of the drug is within microparticles.

25. The process of claim 1, further comprising placing an imaging agent into the hydrogel at a concentration effective to provide visibility of the punctal plug with a machine-aid.

26. The process of claim 25 wherein the imaging agent is a fluorescent compound.

29. The process of claim 1, wherein the drug comprises a corticosteroid.

31. The process of claim 1, wherein the prosthesis consists essentially of the hydrogel, the drug, and an agent that is selected from the group consisting of an imaging agent and a visualization agent.

15. A method of treating an eye condition of an eye with a drug comprising:

placing a covalently-crosslinked, stretched, and dehydrated synthetic hydrogel in a canaliculus of the eye and thereby blocking or reducing tear flow through the canaliculus, with the drug being dispersed within the hydrogel,

with the dehydrated hydrogel absorbing physiological water to swell and directly contact a tissue of the canaliculus in an expanded state and having a proximal face in fluid communication with a tear film of the eye, and

wherein the hydrogel, when hydrated in the canaliculus, releases an amount of the drug effective to treat the eye condition over a time of at least about six days as measurable by a concentration of the drug in a tear film of the eye.

16. The method of claim 15 further comprising providing a visualization agent in the hydrogel at a concentration effective to provide visibility of the agent to the patient without a machine-aid.

17. The method of claim 15, with the hydrogel spontaneously degrading by chemical hydrolysis in water.

18. The method of claim 15, 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.

19. The method of claim 17, 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 precursor 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.

20. The method of claim 15, wherein the drug is chosen from the group consisting of latanoprost, travoprost, moxifloxacin, brinzolamide betaxolol, ciprofloxacin, travoprost, flluorometholone, bimatoprost, prednisolone, cyclosporine, loteprednol etabonate, pegaptanib, azelastine, and timolol.

21. The method of claim 15, wherein the drug comprises a prostaglandin analogue.

22. The method of claim 15, wherein the condition is chosen from the group consisting of elevated intraocular pressure in patients suffering from open angle glaucoma, ocular hypertension, a presence of S. aureu, a presence of S. epidermidis, age-related macular degeneration (AMD), cystoid macular edema (CME), diabetic macular edema (DME), and retinal vein occlusion.

23. The method of claim 15, wherein the drug is free of encapsulating materials.

24. The method of claim 15, wherein at least some of the drug is within microparticles.

27. The method of claim 15, further comprising placing an imaging agent into the hydrogel at a concentration effective to provide visibility of the punctal plug with a machine-aid.

28. The method of claim 27 wherein the imaging agent is a fluorescent compound.

30. The method of claim 15, wherein the drug comprises a corticosteroid.