Ophthalmic System for Sustained Release of Drug to Eye

• US 20140121612A1
• Filed: 10/25/2013
• Published: 05/01/2014
• Est. Priority Date: 10/26/2012
• Status: Active Grant

• Current Assignee: ForSight VISION5, Inc. (Abbvie Incorporated)
• Original Assignee: ForSight VISION5, Inc. (Abbvie Incorporated)
• Inventors: Alster, Yair, Reich, Cary J., Rubin, Anne Brody
• Granted Patent: US 9,750,636 B2
• Time in Patent Office: Days
• US Class Current: 604/300
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: Y10T 156/1036 Bending of one piece blank and joining edges to form article

Abstract

Disclosed is an ocular device including a first structure formed of a first material providing a first shape to the ocular device prior to positioning the ocular device on the surface of the eye, a second structure formed of a second, different material having a tubular structure and a lumen through which the first structure extends, and at least one therapeutic agent is dispersed within the second material of the second structure. The first shape of the ocular device conforms to a second, different shape after positioning the ocular device on the surface of the eye. Upon being removed from the eye, the ocular device retains the second shape or changes to a third shape different from both the first shape and the second shape. Related apparatus, systems and method are described.

Claims

1. An ocular device configured to be positioned on a surface of the eye at least partially underneath at least one of the upper and lower eyelids and outside a cornea of the eye for delivering at least one therapeutic agent to an eye for an extended period of time, the device comprising:

a first structure formed of a first material providing a first shape to the ocular device prior to positioning the ocular device on the surface of the eye;

a second structure formed of a second material having a tubular structure and a lumen through which the first structure extends, wherein the second material is different from the first material; and

at least one therapeutic agent dispersed within the second material of the second structure,

wherein the first shape of the ocular device conforms to a second, different shape after positioning the ocular device on the surface of the eye, and wherein upon being removed from the eye, the ocular device retains the second shape or changes to a third shape, wherein the third shape is different from both the first shape and the second shape.

2. An ocular device as in claim 1, wherein the tubular structure has a cross-sectional shape selected from the group consisting of circular, lentoid, figure-eight, horseshoe, oval, oblong, rounded rectangle, star or gear-shaped.

3. An ocular device as in claim 1, wherein the first structure is thermally fused into a ring shape after being threaded through the lumen of the second structure.

4. An ocular device as in claim 1, wherein the second structure formed of a second material is molded into two or more tubular structures, wherein each of the two or more tubular structures has a lumen through which the first structure extends.

5. An ocular device as in claim 4, wherein a first of the two or more tubular structures is formulated to release the at least one therapeutic agent and wherein a second of the two or more tubular structures is formulated to release the at least one therapeutic agent or a second, different therapeutic agent.

6. An ocular device as in claim 1, wherein the first structure determines the first shape, the second shape and the third shape.

7. An ocular device as in claim 1, wherein the second shape is a shape of at least a portion of the conjunctiva of the eye.

8. An ocular device as in claim 1, wherein the second shape is a shape of at least a portion of the bony orbit of the eye.

9. An ocular device as in claim 7, wherein the second shape is a shape of at least a portion of bony orbit of the eye.

10. An ocular device as in claim 1, wherein the ocular device resists deflection away from the second shape upon being removed from the eye.

11. An ocular device as in claim 1, wherein the first shape is an annular shape positioned substantially within a first plane and the second and third shapes are positioned at least partially outside of the first plane.

12. An ocular device as in claim 1, wherein the second shape corresponds to a surface of a saddle.

13. An ocular device as in claim 1, wherein the second shape has an outer contour that corresponds to an outer contour of a saddle.

14. An ocular device as in claim 1, wherein the ocular device changes from the first shape to the second shape over a period of about 20 minutes to about 24 hours.

15. An ocular device as in claim 1, wherein the first material comprises a material configured to repeatedly become plastic upon exposure to heat, liquid, or pressure.

16. An ocular device as in claim 1, wherein the first material comprises a thermoplastic material.

17. An ocular device as in claim 16, wherein the first material comprises polypropylene.

18. An ocular device as in claim 1, wherein the second material comprises a silicone material.

19. An ocular device as in claim 18, wherein only the second material comprises the at least one therapeutic agent.

20. An ocular device as in claim 1, wherein the at least one therapeutic agent comprises an agent selected from the group consisting of bimatoprost, travoprost, latanoprost, tafluprost, NSAID, steroid, antihistamine, carbonic anhydrase inhibitor (CAI), dorzolamide, cyclosporine, antibiotic, doxycycline, tetracycline, azithromycin, fatty acid, long chain fatty acid, fatty alcohol, cetyl alcohol, stearyl alcohol, non-penetrating steroid, free acid of steroid, lipid, ketorolac, silicone oil, olopatadine, prostaglandin, prostaglandin analog, prostamide, small-molecule integrin antagonist, lifitegrast, loteprednol, and fluoromethalone or a combination thereof.

21. An ocular device as in claim 1, wherein the at least one therapeutic agent comprises a prostaglandin analogue.

22. An ocular device as in claim 21, wherein the prostaglandin analogue comprises at least one of bimatoprost, latanoprost, travoprost, and tafluprost.

23. An ocular device as in claim 1, wherein the at least one therapeutic agent is for lowering the intraocular pressure of the eye.

24. An ocular device as in claim 1, wherein the at least one therapeutic agent is for treating dry eye.

25. An ocular device as in claim 24, wherein the at least one therapeutic agent comprises at least one of cyclosporine, steroid, loteprednol, fluoromethalone, non-penetrating steroid, free acid of steroid, non-steroidal anti-inflammatory, ketorolac, small-molecule integrin antagonist, lifitegrast, doxycycline, azithromycin, lipid, fatty alcohol, cetyl alcohol, stearyl alcohol, fatty acid, long chain fatty acid, oil, or silicone oil.

26. An ocular device as in claim 1, wherein the at least one therapeutic agent comprises a steroid.

27. An ocular device as in claim 26, wherein the steroid comprises at least one of loteprednol or fluoromethalone.

28. An ocular device configured to be positioned on a surface of the eye at least partially underneath at least one of the upper and lower eyelids and outside a cornea of the eye for delivering at least one therapeutic agent to an eye for an extended period of time, the device comprising:

a first structure formed of a first material providing a first shape to the ocular device prior to positioning the ocular device on the surface of the eye;

a second structure formed of a second material having a tubular structure with a lumen through which the first structure extends, wherein the second material is different from the first material; and

at least one therapeutic agent dispersed within the first material of the first structure,

wherein the first shape of the ocular device conforms to a second, different shape after positioning the ocular device on the surface of the eye, and wherein upon being removed from the eye, the ocular device retains the second shape or changes to a third shape, wherein the third shape is different from both the first shape and the second shape.

29. A method of manufacturing an ocular device configured to be positioned on a surface of the eye at least partially underneath at least one of the upper and lower eyelids and outside a cornea of the eye for delivering at least one therapeutic agent to an eye for an extended period of time, the method comprising:

forming a support structure from a length of a first material having a first end region and a second end region into a first shape, wherein the first shape of the support structure provides an overall shape to the ocular device prior to positioning the ocular device on the surface of the eye;

dispersing at least one therapeutic agent into a second material to create a drug matrix, wherein the second material is different from the first material;

molding the drug matrix into a tubular structure having lumen; and

threading the tubular structure over the length the support structure such that the support structure extends through the lumen of the tubular structure,

wherein the first shape conforms to a second, different shape after positioning the ocular device onto the surface of the eye, and wherein upon being removed from the eye, the ocular device retains the second shape or changes to a third shape, wherein the third shape is different from both the first shape and the second shape.

30. The method of claim 29, further comprises fusing the first end region of the length to the second end region of the length after the support structure is threaded through the lumen of the tubular structure.

31. The method of claim 29, wherein fusing comprises thermally welding the first and second end regions together.

32. The method of claim 29, further comprising thermoforming the length into the first shape by wrapping the length over a mandrel having a diameter.

33. The method of claim 32, wherein the diameter is at least about 24 mm, at least about 26 mm, or at least about 29 mm.

34. The method of claim 29, wherein the support structure determines the first shape, the second shape and the third shape of the ocular device.

35. The method of claim 29, wherein the first shape is an annular shape positioned substantially within a first plane and the second and third shapes are positioned at least partially outside of the first plane.

36. The method of claim 29, wherein the ocular device changes from the first shape to the second shape over a period of about 20 minutes to about 24 hours.

37. The method of claim 29, wherein the first material comprises a material configured to repeatedly become plastic upon exposure to heat, liquid, or pressure.

38. The method of claim 29, wherein the first material comprises a thermoplastic material.

39. The method of claim 38, wherein the first material comprises polypropylene.

40. The method of claim 29, wherein the second material comprises a silicone material.

41. The method of claim 29, wherein the at least one therapeutic agent comprises an agent selected from the group consisting of bimatoprost, travoprost, latanoprost, tafluprost, NSAID, steroid, antihistamine, carbonic anhydrase inhibitor (CAI), dorzolamide, cyclosporine, antibiotic, doxycycline, tetracycline, azithromycin, fatty acid, long chain fatty acid, fatty alcohol, cetyl alcohol, stearyl alcohol, non-penetrating steroid, free acid of steroid, lipid, ketorolac, silicone oil, olopatadine, prostaglandin, prostaglandin analog, prostamide, small-molecule integrin antagonist, lifitegrast, loteprednol, and fluoromethalone or a combination thereof.

42. The method of claim 29, wherein the tubular structure has a cross-sectional shape selected from the group consisting of circular, lentoid, figure-eight, horseshoe, oval, oblong, rounded rectangle, star or gear-shaped.

43. The method of claim 29, wherein the tubular structure has a cross-sectional diameter of approximately 1 mm.

44. The method of claim 29, further comprising releasing the at least one therapeutic agent from the drug matrix into the eye.

45. The method of claim 44, further comprising dispersing at least a second therapeutic agent into a second amount of the second material to create a second amount of drug matrix and molding the second amount of drug matrix into at least a second tubular structure having a second lumen.

46. The method of claim 45, further comprising threading the at least a second tubular structure over the length of the support structure such that the support structure extends through the second lumen of the at least a second tubular structure.

47. The method of claim 46, further comprising releasing the at least a second therapeutic agent from the second amount of drug matrix.

48. The method of claim 47, wherein the at least a second therapeutic agent is the same as the at least one therapeutic agent.

49. The method of claim 47, wherein the at least a second therapeutic agent is different from the at least one therapeutic agent.

50. The method of claim 47, wherein the drug matrix releases the at least one therapeutic agent into the eye at a first elution rate and wherein the second amount of drug matrix releases the at least a second therapeutic agent into the eye at a second elution rate.

51. The method of claim 50, wherein the first elution rate and the second elution rate are the same.

52. The method of claim 50, wherein the first elution rate and the second elution rate are different.