BIODEGRADABLE ALPHA-2 AGONIST POLYMERIC IMPLANTS AND THERAPEUTIC USES THEREOF

• US 20100124565A1
• Filed: 11/17/2008
• Published: 05/20/2010
• Est. Priority Date: 11/17/2008
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: SPADA, Lon T., Robinson, Michael R., Ghebremeskel, Alazar N.
• Granted Patent: US 9,095,506 B2
• Time in Patent Office: Days
• US Class Current: 424/428
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• 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: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics

Abstract

Biocompatible intraocular implants include an alpha-2 adrenergic receptor agonist and a polymer associated with the alpha-2 adrenergic receptor agonist to facilitate release of the alpha-2 adrenergic receptor agonist into an eye for an extended period of time. The alpha-2 adrenergic receptor agonist may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The implants can be placed in an eye to treat one or more ocular conditions, such as an ocular vasculopathy or glaucoma, including reduction of an elevated intraocular pressure.

Claims

1. A biodegradable implant adapted for intraocular use, the implant comprising:

(a) more than 50 weight percent alpha-2 adrenergic receptor agonist, and;

(b) a biodegradable polymer which is a mixture of;

(i) an ester end-capped poly (D,L-lactide) polymer, and

(ii) an ester end-capped poly (D,L-lactide-co-glycolide) polymer.

2. The implant of claim 1, wherein the implant comprises about 60 weight % alpha-2 adrenergic receptor agonist, about 30 weight % an ester end-capped poly (D,L-lactide) polymer, and about 10 weight % ester end-capped poly (D,L-lactide-co-glycolide) polymer.

3. The implant of claim 1, wherein the ester end-capped poly (D,L-lactide) polymer comprises two different ester end-capped poly (D,L-lactide) polymers.

4. The implant of claim 1, wherein the alpha-2 adrenergic receptor agonist is brimonidine.

5. The implant of claim 4, wherein the brimonidine is brimonidine free base.

7. The implant of claim 1, wherein the implant has a bar or disc shape.

6. A biodegradable implant adapted for intraocular use, the implant comprising:

(a) about 60 weight percent brimonidine free base, and;

(b) a biodegradable polymer which is a mixture of;

(i) about 15 weight % a first ester end-capped poly (D,L-lactide) polymer,

(ii) about 15 weight % a second ester end-capped poly (D,L-lactide) polymer which is different from the first ester end-capped poly (D,L-lactide) polymer, and

(iii) about 10 weight % an ester end-capped poly (D,L-lactide-co-glycolide) polymer.

8. A biodegradable implant adapted for intraocular use, the implant comprising:

(a) brimonidine tartrate;

(b) brimonidine free base;

(c) a biodegradable polymer which is a mixture of;

(i) a first ester end-capped poly (D,L-lactide) polymer,

(ii) a second ester end-capped poly (D,L-lactide) polymer, and

(iii) an acid end-capped poly (D,L-lactide) polymer.

9. The implant of claim 8, wherein the first and second ester end-capped poly (D,L-lactide) polymers are different ester end-capped poly (D,L-lactide) polymers.

10. The implant of claim 9, wherein the implant comprises about 50 weight % brimonidine, about 20 weight % first ester end-capped poly (D,L-lactide) polymer, and 20 weight % second ester end-capped poly (D,L-lactide) polymer, and about 10 weight % acid end-capped poly (D,L-lactide) polymer.

11. The implant of claim 8, wherein the implant comprises about 40 weight % brimonidine free base.

12. The implant of claim 8, wherein the implant comprises about 10 weight % brimonidine tartrate.

14. The implant of claim 8, wherein the implant has a bar or disc shape.

13. A biodegradable implant adapted for intraocular use, the implant comprising:

(a) about 40 weight % brimonidine free base.

(b) about 10 weight % brimonidine tartrate.

(c) a biodegradable polymer which is a mixture of;

(i) about 20 weight % first ester end-capped poly (D,L-lactide) polymer,

(ii) about 20 weight % a second ester end-capped poly (D,L-lactide) polymer, and

(iii) about 10 weight % an acid end-capped poly (D,L-lactide) polymer.

15. A method for treating glaucoma comprising the step of intraocular administration of a biodegradable intraocular implant comprising:

(a) about 60 weight percent brimonidine free base, and;

(b) a biodegradable polymer which is a mixture of;

(i) about 15 weight % a first ester end-capped poly (D,L-lactide) polymer,

(ii) about 15 weight % a second ester end-capped poly (D,L-lactide) polymer which is different from the first ester end-capped poly (D,L-lactide) polymer, and

(iii) about 10 weight % an ester end-capped poly (D,L-lactide-co-glycolide) polymer.

16. A method for treating glaucoma comprising the step of intraocular administration of a biodegradable intraocular implant comprising:

(a) about 40 weight % brimonidine free base.

(b) about 10 weight % brimonidine tartrate.

(c) a biodegradable polymer which is a mixture of;

(i) about 20 weight % first ester end-capped poly (D,L-lactide) polymer,

(ii) about 20 weight % a second ester end-capped poly (D,L-lactide) polymer, and

(iii) about 10 weight % an acid end-capped poly (D,L-lactide) polymer.