Ocular implant made by a double extrusion process

• US 20050048099A1
• Filed: 08/13/2004
• Published: 03/03/2005
• Est. Priority Date: 01/09/2003
• Status: Abandoned Application

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Nivaggioli, Thierry, Shiah, Jane-Guo, Weber, David A., Peng, Lin, Bhagat, Rahul, Chou, David
• Application Number:
  US10/918,597
• Publication Number:
  US 20050048099A1
• Time in Patent Office: Days
• US Class Current: 424/428
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• 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 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/204 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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

Abstract

The invention provides biodegradable implants sized for implantation in an ocular region and methods for treating medical conditions of the eye. The implants are formed from a mixture of hydrophilic end and hydrophobic end PLGA, and deliver active agents into an ocular region without a high burst release.

Claims

1. A bioerodible implant for treating an ocular condition comprising an active agent dispersed within a biodegradable polymer matrix, wherein at least about 75% of the particles of the active agent have a diameter of less than about 10 μ

m.

2. The implant of claim 1, wherein at least about 99% of the particles of the active agent have a diameter of less than about 20 μ

m.

3. The bioerodible implant of claim 1 wherein the active agent is selected from the group consisting of ace-inhibitors, endogenous cytokines, agents that influence basement membrane, agents that influence the growth of endothelial cells, adrenergic agonists or blockers, cholinergic agonists or blockers, aldose reductase inhibitors, analgesics, anesthetics, antiallergics, anti-inflammatory agents, steroids, antihypertensives, pressors, antibacterials, antivirals, antifungals, antiprotozoals, anti-infective agents, antitumor agents, antimetabolites, and antiangiogenic agents.

4. The bioerodible implant of claim 1 wherein the active agent comprises an anti-inflammatory agent or any derivative thereof.

5. The bioerodible implant of claim 1 wherein the active agent comprises a steroidal anti-inflammatory agent or any derivative thereof.

6. The bioerodible implant of claim 4 wherein the active agent is selected from the group consisting of cortisone, dexamethasone, fluocinolone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone, and any derivative thereof.

7. The bioerodible implant of claim 1 wherein the active agent comprises dexamethasone.

8. The bioerodible implant of claim 1 wherein the implant is sized for implantation in an ocular region.

9. The bioerodible implant of claim 8 wherein the ocular region is selected from the group consisting of the anterior chamber, the posterior chamber, the vitreous cavity, the choroid, the suprachoroidal space, the conjunctiva, the subconjunctival space, the episcleral space, the intracorneal space, the epicorneal space, the sclera, the pars plana, surgically-induced avascular regions, the macula, and the retina.

10. The bioerodible implant of claim 9 wherein the ocular region is the vitreous cavity.

11. A bioerodible implant for treating an ocular condition comprising a steroid active agent dispersed within a biodegradable polymer matrix, wherein at least about 75% of the particles of the steroid active agent have a diameter of less than about 20 μ

m.

12. The bioerodible implant of claim 11 wherein the steroid active agent is selected from the group consisting of cortisone, dexamethasone, fluocinolone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone, and any derivative thereof.

13. The bioerodible implant of claim 12 wherein the steroid active agent comprises dexamethasone.

14. A method for making a bioerodible implant for treating an ocular condition of the eye, the method comprising a plurality of extrusions of a biodegradable polymer.

15. The method of claim 14 further comprising the step of milling the biodegradable polymer prior to the extrusion.

16. The method of claim 14, wherein the biodegradable polymer comprises poly(lactic-co-glycolic)acid (PLGA) copolymer.

17. The method of claim 16 wherein the ratio of lactic to glycolic acid monomers is about 50/50 weight percentage.

18. The bioerodible implant of claim 16 wherein the PLGA copolymer is about 20 to about 90 weight percent of the bioerodible implant.

19. The method of claim 18 wherein the PLGA copolymer is about 40 percent by weight of the bioerodible implant.

21. A bioerodible implant for treating an ocular condition made by the method of claim 14.

20. A method for making a bioerodible implant for treating an ocular condition, the method comprising the steps of:

(a) milling a biodegradable polymer;

(b) blending the milled biodegradable polymer and particles of an active agent, to thereby obtain a blended mixture of the milled biodegradable polymer and the particles of the active agent, wherein at least about 75% of the particles of the active agent have a diameter of less than about 20 μ

m;

(c) carrying out a first extrusion of the blended mixture, to thereby obtain a first extrusion product;

(d) pelletizing the first extrusion product, and;

(e) carrying out a second extrusion of the pelletized first extrusion product, thereby obtaining a bioerodible implant for an ocular condition.