Steroid-containing sustained release intraocular implants and related methods

• US 8,257,730 B2
• Filed: 04/29/2005
• Issued: 09/04/2012
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Huang, Glenn T., Nivaggioli, Thierry, Spada, Lon T., Sugimoto, Hiroshi, Chang, James N., Olejnik, Orest, Blanda, Wendy M
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US11/118,288
• Publication Number:
  US 20050244474A1
• Time in Patent Office: 2,685 Days
• Field of Search: None
• US Class Current: 424/427
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics

Abstract

Biocompatible intraocular implants include a steroid and a polymer associated with each other to facilitate release of the steroid into an eye for a period of time greater than about two months. The steroid may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the steroid may be associated with a polymeric coating having one or more openings effective to permit the steroid to be released into an external environment. The implants may be placed in an eye to treat one or more ocular conditions. The steroid is released from the implant for more than about two months, and may be release for more than several years.

Claims

1. A biodegradable intraocular implant comprising a steroid associated with a biodegradable polymer in the form of an intraocular implant, the implant having a steroid release-rate profile, the release-rate profile having a first portion in which the steroid is released substantially independently of a hydrolytic property of the biodegradable polymer, and a second portion in which the steroid release is more dependent on the hydrolytic property of the biodegradable polymer than during the first portion, wherein the biodegradable polymer comprises a combination of a slow degrading poly(D,L-lactide) polymer and a fast degrading poly(D,L-lactide-co-glycolide) polymer, wherein the slow degrading poly(D,L-lactide) polymer has terminal free acid groups and a molecular weight of about 10-20 kD and the fast degrading poly(D,L-lactide-co-glycolide) polymer has a 50:

50 D,L-lactide to glycolide ratio, terminal free acid groups, and a molecular weight of about 9-40 kD.

2. The implant of claim 1, wherein the steroid is dexamethasone.

3. The implant of claim 1, wherein the first portion of the release-rate profile corresponds to a time period from about 1 day to about 30 days after placement of the implant in a liquid environment.

4. The implant of claim 3, wherein the second portion corresponds to a time period from about 30 days to about 90 days after placement of the implant in the liquid environment.

5. The implant of claim 1, wherein the first portion of the release-rate profile corresponds to a time period when less than 10% of the steroid is released from the implant.

6. The implant of claim 5, wherein the second portion corresponds to a time period when less than 40% of the steroid is released from the implant.

7. The implant of claim 5, wherein the second portion corresponds to a time period when less than 100% of the steroid is released from the implant.

8. The implant of claim 1, wherein the implant releases the steroid in a therapeutically effective amount without the patient developing a cataract.

9. A biodegradable intraocular implant comprising a steroid associated with a biodegradable polymer in the form of an intraocular implant, the implant having a steroid release-rate profile, the release-rate profile having a first portion in which the steroid is released substantially independently of a hydrolytic property of the biodegradable polymer, and a second portion in which the steroid release is more dependent on the hydrolytic property of the biodegradable polymer than during the first portion, wherein said biodegradable polymer comprises a slow degrading poly(lactide) polymer and a fast degrading poly(lactide-coglycolide) polymer, wherein the poly(lactide-co-glycolide) and poly(lactide) polymers have terminal free acid groups.

10. The implant of claim 9, wherein the steroid is selected from the group consisting of beclomethasone, beclomethasone dipropionate, and dexamethasone.

11. The implant of claim 9, wherein the steroid is beclomethasone dipropionate.