DRUG ELUTING OCULAR IMPLANT

• US 20130289467A1
• Filed: 11/22/2011
• Published: 10/31/2013
• Est. Priority Date: 11/24/2010
• Status: Active Grant

• Current Assignee: DOSE Medical Corporation (Glaukos Corporation)
• Original Assignee: DOSE Medical Corporation (Glaukos Corporation)
• Inventors: Haffner, David, Curry, Ken, Heitzmann, Harold, Applegate, David
• Granted Patent: US 9,668,915 B2
• Time in Patent Office: Days
• US Class Current: 604/8
• CPC Class Codes: A61F 2210/0061 swellable
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• 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 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence

Abstract

Disclosed herein are drug delivery devices and methods for the treatment of ocular disorders requiring targeted and controlled administration of a drug to an interior portion of the eye for reduction or prevention of symptoms of the disorder. The devices are capable of controlled release of one or more drugs and may also include structures which allow for treatment of increased intraocular pressure by permitting aqueous humor to flow out of the anterior chamber of the eye through the device.

Claims

1. A drug delivery ocular implant comprising:

an elongate outer shell having a proximal end, a distal end, said outer shell being shaped to define an interior lumen;

at least a first active drug positioned within said interior lumen,

wherein said first active drug is present as one or more micro-tablets,

wherein said micro-tablets have a density of about 0.7 g/cc to about 1.6 g/cc,

wherein said micro-tablets have dimensions allowing passage of the micro-tablets through a conduit having an inner diameter of about 23 to 25 gauge,

wherein said outer shell comprises a first thickness; and

wherein said outer shell comprises one or more regions of drug release.

2. The implant of claim 1, wherein said micro-tablets have a minor axis of about 0.28 to 0.31 mm and a major axis of about 0.8 to 1.1 mm.

3. The implant of claim 1, wherein said elongate shell is formed by extrusion.

4. The implant of claim 1, wherein said elongate shell comprises a biodegradable polymer.

5. The implant of claim 1, wherein said first active drug is present in an amount of at least 70% by weight of a total weight of the one or more micro-tablets, wherein said micro-tablets have a surface area to volume ratio of about 13 to 17, and wherein said micro-tablets have an aspect ratio of length to diameter of about 2.8 to 3.6.

9. The implant of claim 1, wherein said micro-tablets are configured to balance osmotic pressure between said interior lumen and the ocular environment external to an implant after implantation.

10. The implant of claim 1, wherein said micro-tablets are coated with a polymeric coating that regulates the release of said first active drug from said micro-tablet.

12. The implant of claim 1, wherein said outer shell is permeable or semi-permeable to said first active drug, thereby allowing at least about 5% of total the elution of the first active drug to occur through the portions of the shell having said first thickness.

13. The implant of claim 1, wherein said first active drug is an anti-angiogenesis agent selected from the group consisting of angiostatin, anecortave acetate, thrombospondin, VEGF receptor tyrosine kinase inhibitors and anti-vascular endothelial growth factor (anti-VEGF) drugs.

15. The implant of claim 13, wherein said anti-VEGF drugs are selected from the group consisting of ranibizumab, bevacizumab, pegaptanib, sunitinib and sorafenib.

17. The implant of claim 1, wherein said outer shell comprises a polysiloxane-containing polyurethane elastomer.

19. The implant of claim 1, wherein said regions of drug release are configured to allow a different rate of drug elution as compared to said elution through the outer shell, and wherein the overall rate of elution of said first active drug out of the implant is greater in the distal region of the implant.

22. The implant of claim 1, wherein the one or more regions of drug release comprise one or more of regions of reduced thickness shell material, one or more orifices passing through the outer shell, or combinations thereof.

26. The implant according to claim 1, wherein the elution of said first active drug from said implant continues for at least a period of at least one year.

27. The implant of claim 1, further comprising a lumen configured to transport ocular fluid from a first location in an eye to one or more other locations, thereby reducing intraocular pressure.

28. A method of treating an ocular condition or disorder in an intraocular target tissue comprising:

making an opening in the temporal portion of an eye to access an anterior chamber of the eye;

advancing a delivery device associated with the drug delivery ocular implant of claim 1 through the opening and across the anterior chamber of the eye,

inserting the drug delivery ocular implant into eye tissue;

positioning said implant such that at least one of said one or more regions of drug release are located proximate an intraocular target,

the intraocular target is in the posterior chamber of the eye; and

withdrawing the delivery device from the eye, wherein drug elutes from the implant in sufficient quantity to treat an ocular condition or disorder.

30. The method of claim 28, wherein the intraocular target is selected from the group consisting of the macula, the retina, the optic nerve, the ciliary body, and the intraocular vasculature.

31. The method of claim 28, wherein the first active drug elutes from the implant so as to achieve a therapeutic effect for a period of at least one year.

6. (canceled)

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36. (canceled)

37. A system for administering a therapeutic agent to an damaged or diseased eye, comprising:

an ocular implant delivery apparatus comprising;

a proximal end;

a distal end;

a cannula having an inner diameter of about 23 to 25 gauge;

an ocular implant comprising;

an elongate outer shell having a proximal end, a distal end, said outer shell being shaped to define an interior lumen,

wherein said interior lumen is suitable for receiving one or more micro-tablets,

wherein said outer shell comprises a first thickness,

wherein said outer shell comprises one or more regions of drug release; and

a therapeutic agent formed in at least one micro-tablet, said agent having anti-vascular endothelial growth factor (VEGF) effects,

wherein said anti-VEGF agent is lyophilized prior to formation of the micro-tablets,

wherein said anti-VEGF agent comprises at least 70% by weight of the total weight of each micro-tablet;

and

wherein each micro-tablet has a density of about 0.7 g/cc to about 1.6 g/cc.

38. The system of claim 37, wherein said micro-tablets have an aspect ratio of length to diameter of about 2.8 to 3.6.

39. A method for the intravitreal injection of an agent for the treatment of an ocular disorder, comprising:

advancing to the surface of the sclera of an eye a delivery apparatus comprising;

a proximal end;

a distal end;

a cannula having an inner diameter of about 23 to 25 gauge and containing one or more micro-tablets comprising a therapeutic agent having anti-vascular endothelial growth factor (VEGF) effects,

wherein said micro-tablets have a minor axis of about 0.28 to 0.31 mm and a major axis of about 0.8 to 1.1 mm,

wherein said wherein said micro-tablets have a density of about 0.7 g/cc to about 1.6 g/cc; and

an activator that functions to expel the contents of said cannula from said apparatus via passage through said proximal end;

piercing said scleral surface to create a hole in said sclera,

wherein said hole within said sclera is sufficiently small to be self-healing;

further advancing said delivery apparatus thru said hole such that said proximal end is within the vitreal cavity of said eye;

activating said activator to expel said anti-VEGF micro-tablets; and

withdrawing said apparatus from said eye, thereby treating said disorder by the delivery of said anti-VEGF micro-tablets.

40. The method of claim 39, wherein said piercing of said sclera is performed using an apparatus have a sharpened proximal end.

41. (canceled)