Sustained release device and method for ocular delivery of adrenergic agents

• US 20040208910A1
• Filed: 01/22/2004
• Published: 10/21/2004
• Est. Priority Date: 04/26/2000
• Status: Abandoned Application

• Current Assignee: Control Delivery Systems Inc. (EyePoint Pharmaceuticals, Inc.)
• Original Assignee: Control Delivery Systems Inc. (EyePoint Pharmaceuticals, Inc.)
• Inventors: Guo, Hong, Ashton, Paul
• Application Number:
  US10/762,439
• Publication Number:
  US 20040208910A1
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• 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 31/382 having six-membered rings, e.g. thioxanthenes thiothixene A61K31/496
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/542 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• 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 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2853 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/436 of receptors
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence

Abstract

The invention provides a device and method for treating and/or preventing raised intraocular pressure, such as that associated with glaucoma or the use of corticosteroids with adrenergic agents. The invention provides insertable sustained-release devices adapted to maintain a therapeutically effective concentration of one or more adrenergic agents for an extended period of time, and a method of use thereof.

Claims

1. A sustained release drug device adapted for implantation in or adjacent to the eye of a patient, the drug delivery device comprising:

(i) an inner drug core comprising an adrenergic agent;

(ii) a first coating on the surface of the drug core, that is substantially impermeable to the passage of the adrenergic agent, having one or more openings therein which permit diffusion of the adrenergic agent, and which is substantially insoluble and inert in body fluids and compatible with body tissues; and

(iii) one or more additional coatings that are permeable to the passage of the adrenergic agent, and which are substantially insoluble and inert in body fluids and compatible with body tissues;

wherein the first and additional coatings are disposed about the inner drug core so as to produce, when implanted, a substantially constant rate of release of the adrenergic agent from the device.

3. The device of claim 1, wherein the impermeable coating has sufficient dimensional stability to be filled with an adrenergic agent core without changing its shape.

5. A method for administering an adrenergic agent to the ciliary body of an eye, the method comprising implanting a sustained-release device according to any one of claims 1-3 or 14 in or adjacent to the eye, whereby the device delivers the adrenergic agent to the ciliary body of the eye, wherein the adrenergic agent concentration in the ciliary body is maintained at a therapeutically effective concentration for a period of at least 30 days.

7. The method of claim 5, wherein the adrenergic agent concentration in the ciliary body is maintained at a therapeutically effective concentration for a period of at least 180 days.

9. The method of claim 5, wherein the adrenergic agent concentration in the ciliary body is maintained at a therapeutically effective concentration for a period of at least 360 days.

10. The device according to any one of claims 1-4, 6, and 8, wherein the adrenergic agent is selected from the group consisting of brimonidine, aapraclonidine, bunazosin, timolol, betaxolol, levobetaxolol, levobunalol, carteolol, isoprenaline, fenoterol, metipranolol, clenbuterol, epinephrine, and dipivefrin.

11. The method according to claim 5, wherein the adrenergic agent is selected from the group consisting of brimonidine, aapraclonidine, bunazosin, timolol, betaxolol, levobetaxolol, levobunalol, carteolol, isoprenaline, fenoterol, metipranolol, clenbuterol, epinephrine, and dipivefrin.

12. The method according to claim 7, wherein the adrenergic agent is selected from the group consisting of brimonidine, aapraclonidine, bunazosin, timolol, betaxolol, levobetaxolol, levobunalol, carteolol, isoprenaline, fenoterol, metipranolol, clenbuterol, epinephrine, and dipivefrin.

13. The method according to claim 9, wherein the adrenergic agent is selected from the group consisting of brimonidine, aapraclonidine, bunazosin, timolol, betaxolol, levobetaxolol, levobunalol, carteolol, isoprenaline, fenoterol, metipranolol, clenbuterol, epinephrine, and dipivefrin.

2. A sustained release drug device adapted for implantation in or adjacent to the eye of a patient, the drug delivery device comprising:

(i) an inner drug core comprising an adrenergic agent;

(ii) a first coating on the surface of the drug core, that is substantially impermeable to the passage of the adrenergic agent, having one or more openings therein which permit diffusion of the adrenergic agent, and which is substantially insoluble and inert in body fluids and compatible with body tissues; and

(iii) one or more additional coatings that are permeable to the passage of the adrenergic agent, and which are substantially insoluble and inert in body fluids and compatible with body tissues;

wherein the impermeable coating has sufficient dimensional stability to be filled with an adrenergic agent core without changing its shape.

4. A method for administering an adrenergic agent to the ciliary body of an eye, the method comprising implanting a sustained-release device in or adjacent to the eye, whereby the device delivers the adrenergic agent to the ciliary body of the eye, wherein the adrenergic agent concentration in the ciliary body is maintained at a therapeutically effective concentration for a period of at least 30 days.

6. The method of claim 4, wherein the adrenergic agent concentration in the ciliary body is maintained at a therapeutically effective concentration for a period of at least 180 days.

8. The method of claim 4, wherein the adrenergic agent concentration in the ciliary body is maintained at a therapeutically effective concentration for a period of at least 360 days.

14. A sustained release drug delivery device adapted for insertion in or adjacent to the eye of a patient, the drug delivery device comprising:

(i) an inner drug core comprising at least one adrenergic agent;

(ii) a coating layer on the surface of the drug core that is substantially impermeable to the passage of the at least one adrenergic agent, having one or more openings therein which permit diffusion of the at least one adrenergic agent, and that is substantially insoluble and inert in body fluids and compatible with body tissues; and

wherein the coating is disposed about the inner drug core so as to produce, when inserted a substantially constant rate of release of the adrenergic agent(s) from the device.

15. The sustained release drug delivery device of claim 14, wherein the inner drug core is admixed with a polymer matrix.

16. The sustained release drug delivery device of claim 15, wherein the polymer matrix is bioerodible.

17. The sustained release drug delivery device of claim 14, wherein the device is formed by co-extruding the inner drug core and the coating layer.

18. A sustained release drug delivery device adapted for insertion in or adjacent to the eye of a patient, the drug delivery device comprising:

(i) an inner drug core comprising at least one adrenergic agent;

(ii) a coating layer on the surface of the drug core that is partially or substantially permeable to the passage of the at least one adrenergic agent, having one or more openings therein which aid diffusion of the at least one adrenergic agent, and that is substantially insoluble and inert in body fluids and compatible with body tissues; and

wherein the coating is disposed about the inner drug core so as to produce, when inserted, a substantially constant rate of release of the at least one adrenergic agent from the device.

19. The sustained release drug delivery device of claim 18, wherein the inner drug core is admixed with a polymer matrix.

20. The sustained release drug delivery device of claim 19, wherein the polymer matrix is bioerodible.

21. The sustained release drug delivery device of claim 20, wherein the device is formed by co-extruding the inner drug core and the coating layer.