Steroid-containing sustained release intraocular implants and related methods

• US 20070031472A1
• Filed: 06/23/2006
• Published: 02/08/2007
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Sugimoto, Hiroshi, Nivaggioli, Thierry, Chang, James, Olejnik, Orest, Blanda, Wendy, Huang, Glenn, Spada, Lon
• Granted Patent: US 8,147,865 B2
• 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 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• 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 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 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• 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 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/436 of receptors
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/148 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• 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: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Biocompatible intraocular implants include a steroid and an auxiliary agent, where the auxiliary agent is present in an amount sufficient to lessen the severity of at least one side effect compared to the use of an otherwise identical implant lacking said auxiliary agent. The steroid and the auxiliary agent may be present on the same intraocular implant or on different implants. The steroid and auxiliary agent 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 containing the steroid and an auxiliary agent may be placed in an eye to treat one or more ocular conditions while reducing the side effects otherwise accompanying steroid use.

Claims

1. A biodegradable intraocular implant, comprising:

a steroid; and

an auxiliary agent, wherein the steroid and the auxiliary agent are associated with a biodegradable polymer in the form of an intraocular implant.

2. The implant of claim 1, wherein the steroid is selected from the group consisting of dexamethasone, fluocinolone, fluocinolone acetonide, triamcinolone, triamcinolone acetonide, salts thereof, and mixtures thereof

3. The implant of claim 1, wherein the biodegradable polymer is a poly(lactide-co-glycolide) polymer.

4. The implant of claim 1, wherein the auxiliary agent is selected from the group consisting of a parasympathomimetic, a sympathomimetic, an alpha agonist, a beta blocker, a carbonic anhydrase inhibitor, a prostaglandin analog, a neuroprotectant, and mixtures thereof.

5. The implant of claim 1, wherein the auxiliary agent is selected from the group consisting of pilocarpone, carbachol, echothiophate, epinephrine, dipivefrin, apracionidine, brimonidine, clonidine, apraclonidine, p-aminoclonidine, oxymetazoline, epinephrine, norepinephrine, and cirazoline, dexmedatomidine, mivazerol, xylazine, medatomidine, memantime, timolol, levobunolol, metipranilol, carteolol, betaxolol, dorzolamine, brinzolamide, dichlorphenamide, latanoprost, bimatoprost, travaprost, unoprostone, and mixtures thereof.

6. The implant of claim 1, wherein the implant comprises a polymeric outer layer which is impermeable to an intraocular fluid.

7. The implant of claim 6, wherein the outer layer comprises a plurality of openings or holes in the polymeric outer layer.

10. A biodegradable intraocular implant system, comprising:

a steroid associated with a biodegradable polymer in the form of a first intraocular implant; and

an auxiliary agent associated with a biodegradable polymer in the form of a second intraocular implant.

11. A biodegradable intraocular implant system, comprising:

a steroid associated with a biodegradable polymeric component in the form of an intraocular implant structured for intravitreal placement in an eye of an individual, the steroid being present in an amount effective in treating an ocular condition of the eye with a reduced toxicity relative to intravitreal injection of a liquid composition containing the same steroid; and

an auxiliary agent associated with a biodegradable polymeric component in the form of an intraocular implant structured for intravitreal placement in an eye of an individual, the auxiliary agent being present in an amount effective to reduce the occurrence of at least one side effect present upon otherwise identical administration of the steroid alone.

12. The implant system of claim 11, wherein the steroid is selected from the group consisting of dexamethasone, fluocinolone, fluocinolone acetonide, triamcinolone, triamcinolone acetonide, salts thereof, and mixtures thereof

13. The implant system of claim 11, wherein the auxiliary agent comprises an antiglaucoma drug is selected from the group consisting of a parasympathomimetic, a sympathomimetic, an alpha agonist, a beta blocker, a carbonic anhydrase inhibitor, a prostaglandin analog, a neuroprotectant, and mixtures thereof.

14. The implant system of claim 11, wherein the implant comprises steroid and auxiliary agent in alternating layers.

15. The implant system of claim 11, wherein the steroid and the auxiliary agent are comprised in the same implant.

16. The implant system of claim 11, wherein the steroid and the auxiliary agent are comprised in different implants.

22. The implant system of claim 11, wherein the steroid and the auxiliary agent are released from the implant intermittently.

17. A method of treating an ocular disease in an eye of a patient comprising

contacting an implant comprising a steroid with an ocular fluid in the eye of the patient;

thereby releasing steroid from the implant into the ocular fluid, and

contacting an implant comprising an auxiliary agent with the ocular fluid in the eye of the patient, thereby releasing auxiliary agent from the implant into the ocular fluid,

wherein the steroid is present in an amount effective in treating the ocular disease, and

wherein the auxiliary agent is present in an amount effective to reduce the occurrence of at least one side effect present upon otherwise identical administration of the steroid alone.

18. The method of claim 17, wherein the auxiliary agent comprises an antiglaucoma drug selected from the group consisting of a parasympathomimetic, a sympathomimetic, an alpha agonist, a beta blocker, a carbonic anhydrase inhibitor, a prostaglandin analog, a neuroprotectant, and mixtures thereof.

19. The method of claim 18, wherein the antiglaucoma drug is selected from the group consisting of pilocarpone, carbachol, echothiophate, epinephrine, dipivefrin, apracionidine, brimonidine, clonidine, apraclonidine, p-aminoclonidine, oxymetazoline, epinephrine, norepinephrine, and cirazoline, dexmedatomidine, mivazerol, xylazine, medatomidine, memantime, timolol, levobunolol, metipranilol, carteolol, betaxolol, dorzolamine, brinzolamide, dichlorphenamide, latanoprost, bimatoprost, travaprost, unoprostone, and mixtures thereof.

20. The method of claim 17, wherein the steroid and the auxiliary agent are released from the implant simultaneously.

21. The implant system of claim 17, wherein the steroid and the auxiliary agent are released from the implant at different times.

23. The method of claim 17, wherein the ocular implant comprising the steroid and the ocular implant comprising the auxiliary agent are the same implant.

24. The method of claim 17, wherein the ocular implant comprising the steroid and the ocular implant comprising the auxiliary agent are different implants.