Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods

• US 20050244470A1
• Filed: 04/30/2004
• Published: 11/03/2005
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Edelman, Jeffrey L., Hughes, Patrick M., Chang-Lin, Joan-En, Nivaggioli, Thierry, Malone, Thomas C., Shiah, Jane Guo, De Vries, Gerald W.
• Granted Patent: US 7,771,742 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer

Abstract

Biocompatible intraocular implants include a tyrosine kinase inhibitor and a biodegradable polymer that is effective to facilitate release of the tyrosine kinase inhibitor into an eye for an extended period of time. The therapeutic agents of the implants may be associated with a biodegradable polymer matrix, such as a matrix that is substantially free of a polyvinyl alcohol. The implants may be placed in an eye to treat or reduce the occurrence of one or more ocular conditions.

Claims

1. A biodegradable intraocular implant comprising:

a tyrosine kinase inhibitor and a biodegradable polymer matrix that releases drug at a rate effective to sustain release of an amount of the tyrosine kinase inhibitor from the implant for at least about one week after the implant is placed in an eye.

2. The implant of claim 1, wherein the tyrosine kinase inhibitor is a compound having the formula

3. The implant of claim 1, wherein the tyrosine kinase inhibitor is a compound having the formula

4. The implant of claim 1, wherein the tyrosine kinase inhibitor is compound having the formula

5. The implant of claim 1, wherein the tyrosine kinase inhibitor is a compound having the formula

6. The implant of claim 1, further comprising an additional ophthalmically acceptable therapeutic agent.

7. The implant of claim 1, wherein the tyrosine kinase inhibitor is dispersed within the biodegradable polymer matrix.

8. The implant of claim 1, wherein the matrix comprises at least one polymer selected from the group consisting of polylactides, poly(lactide-co-glycolides), polycaprolactones, derivatives thereof, and mixtures thereof.

9. The implant of claim 1, wherein the implant comprises a first portion comprising a mixture of the tyrosine kinase inhibitor and a biodegradable polymer, and a different second portion comprising a biodegradable polymer substantially free of the tyrosine kinase inhibitor.

10. The implant of claim 1, wherein the matrix comprises a single type of polymer, and the implant releases the tyrosine kinase inhibitor for about 70 days at a substantially linear rate.

11. The implant of claim 1, wherein the matrix releases drug at a rate effective to more than one month from the time the implant is placed in the vitreous of the eye.

12. The implant of claim 1, wherein the implant is structured to be placed in the vitreous of the eye.

13. The implant of claim 1, wherein the tyrosine kinase inhibitor is provided in an amount from about 40% by weight to about 70% by weight of the implant, and the biodegradable polymer matrix comprises a poly(lactide-co-glycolide) in an amount from about 30% by weight to about 60% by weight of the implant.

14. The implant of claim 1 formed as a rod, a wafer, or a particle.

15. The implant of claim 1 which is formed by an extrusion process.

16. A method of making a biodegradable intraocular implant, comprising the step of:

extruding a mixture of an tyrosine kinase inhibitor and a biodegradable polymer component to form a biodegradable material that degrades at a rate effective to sustain release of an amount of the tyrosine kinase inhibitor from the implant for at least about one week after the implant is placed in an eye.

17. The method of claim 16, wherein mixture consists essentially of a tyrosine kinase inhibitor and a biodegradable polymer.

18. The method of claim 16, further comprising a step of mixing the tyrosine kinase inhibitor with the polymer component before the extrusion step.

19. The method of claim 16, wherein the tyrosine kinase inhibitor and the polymer component are in a powder form.

20. The method of claim 16, wherein the polymer component comprises a polymer selected from the group consisting of polyactides, poly(lactide-co-glycolides), polycaprolactones, and combinations thereof.

21. A method of treating an ocular condition of an eye of a patient, comprising the step of placing a biodegradable intraocular implant in an eye of the patient, the implant comprising a tyrosine kinase inhibitor and a biodegradable polymer matrix, wherein the implant degrades at a rate effective to sustain release of an amount of the tyrosine kinase inhibitor from the implant effective to treat the ocular condition.

22. The method of claim 21, wherein the method is effective to treat a retinal ocular condition.

23. The method of claim 21, wherein the ocular condition is glaucoma.

24. The method of claim 21, wherein the ocular condition is proliferative vitreoretinopathy.

25. The method of claim 21, wherein the implant is placed in the posterior of the eye.

26. The method of claim 21, wherein the implant is placed in the eye with a trocar.

27. The method of claim 21, wherein the implant is placed in the eye with a syringe.

28. The method of claim 21, further comprising a step of administering a therapeutic agent in addition to the tyrosine kinase inhibitor to the patient.