Nasolacrimal Drainage System Implants for Drug Therapy

• US 20070243230A1
• Filed: 04/02/2007
• Published: 10/18/2007
• Est. Priority Date: 03/31/2006
• Status: Active Grant

• Current Assignee: Mati Therapeutics, Inc
• Original Assignee: Forsight Labs, LLC
• Inventors: Gifford, Hanson, Boyd, Stephen, Rapacki, Alan, de Juan, Eugene, Reich, Cary, Deem, Mark
• Granted Patent: US 7,998,497 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61F 2220/0008 Fixation appliances for connecting prostheses to the body
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0087 colour-coded
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/0026 Ophthalmic product dispenser attachments to facilitate positioning near the eye
• CPC Class Codes: A61F 9/00772 Apparatus for restoration of tear ducts
• CPC Class Codes: A61F 9/00781 Apparatus for modifying intraocular pressure, e.g. for glaucoma treatment drainage implants in general A61M27/002
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• CPC Class Codes: A61K 9/0017 Non-human animal skin, e.g. pour-on, spot-on
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

Implant devices, systems and methods for insertion into a punctum of a patient optionally comprises a drug core and a sheath body disposed over the drug core. The drug core includes a therapeutic agent deliverable into the eye, and the sheath defines at least one exposed surface of the drug core. The exposed surface(s) of the drug core may contact a tear or tear film fluid and release the therapeutic agent at therapeutic levels over a sustained period when the implant is implanted for use. The implant may include a retention element to retain the drug core and sheath body near the punctum, optionally comprising a shape memory alloy that can resiliently expand. An occlusive element may be attached to the retention element to at least partially occlude tear flow through the canalicular lumen.

Claims

1. An implant for insertion into a punctum of a patient, the implant comprising:

a drug core having a distal end and a proximal end, the distal end of the drug core having a cross section suitable for insertion through a punctum, the drug core comprising a therapeutic agent deliverable into the eye; and

a sheath disposed over a portion of the drug core to define at least one exposed surface of the drug core, the at least one exposed surface of the drug core located near the proximal end to contact a tear or tear film fluid and release the therapeutic agent at therapeutic levels over a sustained period when the implant is implanted for use.

2. The implant of claim 1 further comprising a retention structure attached to the drug core to retain the drug core near and/or in the punctum.

3. The implant of claim 2 wherein the retention structure is attached to the drug core via the sheath.

4. The implant of claim 2 wherein the retention structure comprises a hydrogel adapted to expand when the retention structure is placed in the punctum.

5. The implant of claim 4 wherein the retention structure comprises an attachment member having an axially oriented surface, the hydrogel capable of expansion to urge against the axially oriented surface to retain the hydrogel while the hydrogel is hydrated.

6. The implant of claim 5 wherein the attachment member comprises at least one of a protrusion, a flange, a rim, or an opening through a portion of the retention structure.

7. The implant of claim 2 wherein the retention structure comprises a flange near the at least one exposed surface to retain the surface near the punctum.

8. The implant of claim 2 wherein the retention structure has a size suitable to fit at least partially within the canalicular lumen.

9. The implant of claim 8 wherein the retention structure is expandable between a small profile configuration suitable for insertion and a large profile configuration to anchor the retention structure in the lumen.

10. The implant of claim 9 wherein the retention structure is attached near the distal end of the drug core.

11. The implant of claim 10 wherein the retention structure slides along the drug core near the proximal end when the retention structure expands from the small profile configuration to the large profile configuration.

12. The implant of claim 9 wherein a length of the retention structure along the drug core is shorter in the large profile configuration than the small profile configuration.

13. The implant of claim 9 wherein the retention structure is resiliently expandable.

14. The implant of claim 9 wherein the small profile has a cross section of no more than about 0.2 mm, and the large profile has a cross section of no more than about 2.0 mm.

15. The implant of claim 9 wherein the retention structure comprises a tubular body having arms separated by slots.

16. The implant of claim 9 further comprising an occlusive element mounted to and expandable with the retention structure to inhibit tear flow.

17. The implant of claim 8 wherein the retention structure is disposed at least partially over the drug core.

18. The implant of claim 8 further comprising an occlusive element to inhibit tear flow through the lumen, wherein the occlusive element covers at least a portion of the retention structure to protect the lumen from the retention structure.

19. The implant of claim 1 wherein the sheath body comprises a layer disposed over the drug core to inhibit release of the therapeutic agent through the layer.

20. The implant of claim 19 wherein the drug core releases the therapeutic agent through the exposed surface.

21. The implant of claim 1 wherein the drug core releases the therapeutic agent at therapeutic levels throughout a time period of at least one week when the implant is implanted with the surface exposed to the tear or tear film fluid.

22. The implant of claim 1 wherein the drug core comprises inclusions of the agent and the agent is soluble in the drug core to provide a substantially uniform release rate when the drug core is implanted.

23. The implant of claim 1 further comprising an occlusive element to inhibit tear fluid flow through the canalicular lumen.

24. The implant of claim 23 wherein the occlusive element is shaped to block tear flow through the canalicular lumen.

25. An implant for insertion into a punctum of a patient, the implant comprising:

a therapeutic agent;

a material to hold the therapeutic agent; and

a retention structure disposed over at least a portion of the material, the retention structure expandable from the material to retain the material near the punctum.

26. The implant of claim 25 wherein the material holds the therapeutic agent in at least one of a reservoir or a matrix.

27. The implant of claim 25 further comprising an occlusive element supported by the retention structure.

28. The implant of claim 27 wherein retention structure is expandable between a small profile configuration suitable for insertion and a large profile configuration to anchor the retention structure in the lumen.

29. The implant of claim 28 wherein the occlusive element expands with the retention structure.

30. A method of treating an eye with a therapeutic agent, the method comprising:

inserting a retention structure and a distal end of a drug core of an implant into a punctum;

delivering a therapeutic agent from the drug core to the eye;

limiting an exposed surface of the drug core near the proximal end of the drug core with a sheath, wherein the exposed surface contacts the tear or tear film fluid and the treatment agent migrates from the exposed surface to the eye over a sustained period while the drug core is retained near the punctum by the retention structure.

31. A method of treating an eye with a therapeutic agent, the method comprising:

inserting a retention structure and a distal end of a drug core through a punctum so that the drug core is retained near the punctum, wherein the drug core comprises a therapeutic agent deliverable to the eye and wherein an exposed surface of the drug core located near the proximal end of the drug core, wherein the exposed surface contacts the tear or tear film fluid and the treatment agent migrates from the exposed surface to the eye over a sustained period while the drug core is retained near the punctum.

32. The method of claim 31 wherein the retention structure expands from a narrow profile configuration to a wide profile configuration.

33. The method of claim 31 wherein the retention structure hydrates when inserted through the punctum to expand from a narrow profile configuration to a wide profile configuration.

34. A method of treating an eye with a therapeutic agent, the method comprising:

inserting a retention structure through a punctum into a canalicular lumen so that a drug core is anchored to the lumen with the retention structure and releases effective amounts of a therapeutic agent into a tear or tear film fluid of the eye;

removing the drug core from the retention structure while the retention structure remains anchored to the lumen; and

attaching a replacement drug core to the retention structure while the retention structure remains anchored to the lumen;

wherein at least one exposed surface of the replacement drug core releases the therapeutic agent at therapeutic levels over a sustained period.

35. A method for treating an eye, the method comprising:

inserting a distal end of an implant into a punctum;

expanding a retention structure of the implant so as to inhibit expulsion of the implant, the expansion of the implant helping to occlude a flow of tear fluid through the punctum;

delivering a therapeutic agent from a proximal end of the implant to the tear fluid adjacent the eye; and

inhibiting delivery of the therapeutic agent distally of the proximal end.

36. The method of claim 35 wherein delivery of the therapeutic agent to the tear is inhibited with a sheath having a portion exposed to the tear fluid.

37. The method of claim 35 wherein the retention structure comprises a superelastic or shape memory alloy.

38. The method of claim 35 wherein the retention structure comprises a hydrogel and extends distally of the drug core.

39. An implant for treating an eye, the eye having a tear fluid and a punctum, the implant comprising:

a drug core having a proximal end, a distal end, and a cross section suitable for insertion into the punctum;

a sheath disposed over the drug core distally of the proximal end; and

;

a swellable material disposed distally of the proximal end, the swellable material adapted to swell after insertion into the punctum to retain the drug core and occlude the tears in fluid communication with the drug core.

40. The implant of claim 39 further comprising wings connected to the sheath near the proximal end of the drug core, wherein the wings are sized remain outside the punctum so as to retain the proximal end of the drug core near the punctum.

41. An implant for treating an eye, the eye having a tear fluid and a punctum, the implant comprising:

a drug core having a proximal end, a distal end, and a cross section suitable for insertion into the punctum;

a sleeve disposed over the drug core at least distally of the proximal end; and

;

a swellable material disposed distally of the proximal end and at least partially covered by the sleeve, the swellable material adapted to swell after insertion into the punctum to retain the drug core and occlude the tears in fluid communication with the drug core.

42. The implant of claim 41 wherein the sleeve comprises tabs to retain the punctal plug upon expansion of the swellable material.

43. A punctal plug for treating an eye, the eye having a tear fluid and a punctum, the plug comprising:

a plug body; and

a drug core inside the plug body, the drug core comprising a mixture of therapeutic agent and a matrix, wherein a surface of the core is exposed to the tear fluid to treat the eye.

44. The implant of claim 43 wherein the drug core is capable of resilient expansion to accommodate a needle inserted therein while the plug is inserted into a punctum of the eye.

45. A punctal plug for treating an eye, the eye having a tear fluid and a punctum, the plug comprising:

an expandable retention element to expand and engage the punctum when positioned in the punctum; and

a body connected to the expandable retention element, the body comprising a protrusion for removal of the retention element from the punctum.

46. The implant of claim 45 wherein the expandable retention element comprises a swellable material and the body is adapted to retain the swellable material while the body is removed.

47. The implant of claim 46 wherein the swellable material comprises a hydrogel.