Ophthalmic system for sustained release of drug to eye

• US 10,456,293 B2
• Filed: 09/01/2017
• Issued: 10/29/2019
• Est. Priority Date: 10/26/2012
• Status: Active Grant

• Current Assignee: ForSight VISION5, Inc. (Abbvie Incorporated)
• Original Assignee: ForSight VISION5, Inc. (Abbvie Incorporated)
• Inventors: Rubin, Anne Brody, Alster, Yair, Reich, Cary J.
• Primary Examiner(s): Klein, Benjamin J
• Application Number:
  US15/694,079
• Publication Number:
  US 20180085254A1
• Time in Patent Office: 788 Days
• 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. 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 creating a drug matrix, wherein the second material is different from the first material;

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

threading the tubular structure over the length of 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.

2. The method of claim 1, wherein forming the support structure comprises thermoforming the support structure into the first shape by wrapping the length over a mandrel having a diameter.

3. The method of claim 2, wherein the support structure is thermoformed into the first shape after threading the tubular structure over the length of the support structure.

4. The method of claim 2, wherein the diameter of the mandrel is at least about 24 mm, at least about 26 mm, or at least about 29 mm.

5. The method of claim 2, wherein the diameter of the mandrel is greater than a maximum diameter of the eye on which the ocular device is to be placed.

6. The method of claim 2, further comprising cutting the support structure having the first shape be between 24 mm and 29 mm.

7. The method of claim 6, further comprising fusing the first end region of the length to the second end region of the length after threading the tubular structure over the length of the support structure.

8. The method of claim 7, wherein fusing comprises thermally welding the first end region and the second end region together.

9. The method of claim 1, further comprising stress-relieving the support structure in an oven.

10. The method of claim 1, wherein the support structure determines the first shape, the second shape and the third shape of the ocular device.

11. The method of claim 1, wherein the support structure has a self-loading resistance to deflection.

12. The method of claim 11, wherein the tubular structure has a self-loading resistance to deflection, the self-loading resistance to deflection of the tubular structure being less than the self-loading resistance to deflection of the support structure.

13. The method of claim 11, wherein the self-loading resistance to deflection of the support structure is within a range from about 0.01 N/mm to about 1 N/mm.

14. The method of claim 11, wherein the self-loading resistance to deflection of the support structure is between about 1 degree and about 60 degrees.

15. The method of claim 1, wherein the support structure is formed to have a self-loading resistance to a deflection angle between a first portion of the support structure and a second portion of the support structure when the first portion is supported and held in place and the weight of the second portion deflects the support structure.

16. The method of claim 1, wherein forming the support structure into the first shape comprises forming the support structure into 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.

17. The method of 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.

18. The method of claim 1, wherein the first material comprises a material configured to repeatedly become plastic upon exposure to heat, liquid, or pressure.

19. The method of claim 1, wherein the first material comprises a thermoplastic material.

20. The method of claim 1, wherein the first material comprises polypropylene.

21. The method of claim 1, wherein the second material comprises a silicone material.

22. The method of claim 1, wherein the second material comprises MED-4830 silicone.

23. The method of 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.

24. The method of claim 1, wherein the at least one therapeutic agent is for lowering the intraocular pressure of the eye.

25. The method of claim 1, wherein the at least one therapeutic agent is for treating dry eye.

26. The method of claim 1, wherein the at least one therapeutic agent comprises at least one of the group consisting 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, and silicone oil.

27. The method of claim 1, wherein the at least one therapeutic agent comprises a steroid.

28. The method of claim 27, wherein the steroid comprises at least one of loteprednol or fluoromethalone.

29. The method of claim 1, wherein molding the drug matrix into the tubular structure comprises forming one or more grooves on an outer surface of the tubular structure.

30. The method of claim 1, wherein molding the drug matrix into the tubular structure comprises molding the lumen to be centered or off-center to the tubular structure.

31. The method of claim 1, wherein molding the drug matrix into the tubular structure comprises molding the drug matrix into a cross-sectional shape selected from the group consisting of circular, lentoid, figure-eight, horseshoe, oval, oblong, rounded rectangle, star, and gear-shaped.

32. The method of claim 1, wherein molding the drug matrix into the tubular structure comprises molding the drug matrix to have a cross-sectional diameter of approximately 1 mm.

33. The method of claim 1, further comprising dispersing 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 a second tubular structure having a second lumen.

34. The method of claim 33, further comprising threading the second tubular structure over the length of the support structure such that the support structure extends through the second lumen of the second tubular structure.

35. The method of claim 34, wherein the second therapeutic agent is the same or different as the at least one therapeutic agent.

36. The method of claim 35, 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 second therapeutic agent into the eye at a second elution rate, wherein the first elution rate and the second elution rate are the same or different.

37. The method of claim 35, wherein a terminal end of the first tubular structure abuts a terminal end of the second tubular structure.

38. The method of claim 35, wherein a terminal end of the first tubular structure is separated a distance from a terminal end of the second tubular structure.

39. The method of claim 35, wherein the first tubular structure comprises the at least one therapeutic agent at a first formulation and the second tubular structure comprises the second therapeutic agent at a second formulation.

40. The method of claim 39, wherein the first formulation allows for a higher drug dose released for a first period of time and the second formulation allows for a lower drug dose released for a second longer period of time.

41. The method of claim 1, wherein molding the drug matrix into the tubular structure comprises increasing a surface area of the tubular structure at a first location relative to a second location of the tubular structure.

42. The method of claim 41, wherein the ocular device has a first rate of release at the first location that is different from a rate of release at the second location.

43. The method of claim 1, wherein the tubular structure has a length that is at least about 1 mm, 2, mm, 4 mm, 6 mm, 8 mm, 10 mm, 12 mm, 14 mm, 16 mm, 18 mm, or greater up to the length of the support structure.

44. The method of claim 1, wherein the tubular structure has an arc length of between about 5 degrees to 75 degrees to approximately 360 degrees of the length of the support structure.

45. The method of claim 1, wherein the lumen has an inner diameter configured to receive the support structure.

46. The method of claim 45, wherein the inner diameter of the lumen is about 0.06 mm, 0.08 mm, 0.11 mm, 0.16 mm, 0.21 mm, 0.31 mm, or 0.36 mm.