INTRAOCULAR DRUG DELIVERY SYSTEMS

• US 20080131484A1
• Filed: 12/01/2006
• Published: 06/05/2008
• Est. Priority Date: 12/01/2006
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Ruiz, Guadalupe, Whitcup, Scott M., Hughes, Patrick M., Blanda, Wendy M., Robinson, Michael R., Orilla, Werhner C.
• Granted Patent: US 8,969,415 B2
• 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 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics

Abstract

Biodegradable implants sized and suitable for implantation in an ocular region or site and methods for treating ocular conditions. The implants provide an extended release of an active agent at a therapeutically effective amount for a period of time between 10 days and one year or longer.

Claims

1. A biocompatible, injectable intraocular drug delivery system comprising:

(a) a plurality of microspheres, and

(b) an aqueous vehicle for the microspheres,

wherein the microspheres consist essentially of;

(1) a therapeutic agent which is an estradiol, and;

(2) one or more biodegradable polymers, all of which biodegradable polymers are polylactic acid (PLA) polymers, and;

wherein the drug delivery system has a viscosity which permits the drug delivery system to be injected into an intraocular location through a 20 to 30 gauge syringe needle.

2. The drug delivery system of claim 1, wherein the estradiol is a 2-methoxyestradiol.

3. The drug delivery system of claim 1, wherein the estradiol comprises from about 20 wt % to about 50 wt % of the weight of the microspheres and the PLA polymer comprises from about 50 wt % to about 80 wt % of the weight of the microspheres.

4. The drug delivery system of claim 1, wherein the PLA polymer is a poly(D,L) lactide polymer.

5. The drug delivery system of claim 1, wherein the PLA polymer has an inherent viscosity of between about 1 dL/gm and about 1.4 dL/gm.

6. The drug delivery system of claim 1, wherein the microspheres have an average diameter between about 2 microns and about 6 microns.

9. The method of claim 1, wherein the intraocular location is a sub-Tenon, subconjunctival or retrobulbar intraocular location.

19. The method of claim 1, wherein the intraocular location is a sub-Tenon, subconjunctival or retrobulbar intraocular location.

7. A biocompatible, injectable intraocular drug delivery system comprising:

(a) a plurality of microspheres with an average diameter between about 2 microns and about 6 microns, and

(b) an aqueous vehicle for the microspheres,

wherein the microspheres consist essentially of;

(1) a 2-methoxyestradiol, wherein the 2-methoxyestradiol comprises from about 20 wt % to about 50 wt % of the weight of the microspheres, and;

(2) one or more biodegradable polymers, all of which biodegradable polymers are poly(D,L)lactide polymers with an inherent viscosity of between about 1 dL/gm and about 1.4 dL/gm, wherein the PLA polymer comprises from about 50 wt % to about 80 wt % of the weight of the microspheres, and;

wherein the drug delivery system can be injected into an intraocular location through a 20 to 26 gauge syringe needle.

8. A method for treating an ocular condition, the method comprising the steps of:

(a) preparing a biocompatible drug delivery system comprising a plurality of microspheres, and an aqueous vehicle for the microspheres,

wherein the microspheres consist essentially of a therapeutic agent which is an estradiol, and one or more biodegradable polymers, all of which biodegradable polymers are polylactic acid (PLA) polymers, and;

(b) injecting the drug delivery system into an intraocular location through a 20 to 26 gauge syringe needle, thereby treating an ocular condition, wherein the method does not result in significant ocular surface hyperemia.

10. A biocompatible, injectable intraocular drug delivery system comprising:

(a) a plurality of microspheres, and

(b) an aqueous vehicle for the microspheres,

wherein the microspheres consist essentially of;

(1) a therapeutic agent which is an alpha 2 adrenergic agonist, and;

(2) one or more biodegradable polymers, all of which biodegradable polymers are polylactic acid (PLA) polymers, and;

wherein the drug delivery system has a viscosity at 20°

C. of between about 15,000 cps and about 100,000 cps which permits the drug delivery system to be injected into an intraocular location through a 24 to 30 gauge syringe needle.

11. The drug delivery system of claim 10, wherein the alpha 2 adrenergic agonist is a brimonidine.

12. The drug delivery system of claim 10, wherein the alpha 2 adrenergic agonist comprises from about 0.5 wt % to about 15 wt % of the microspheres and the PLA polymer comprises from about 85 wt % to about 99.5 wt % of the microspheres.

13. The drug delivery system of claim 10, wherein the PLA polymer is a poly(D,L) lactide polymer.

14. The drug delivery system of claim 10, wherein the PLA polymer has an inherent viscosity of between about 0.4 dL/gm and about 0.8 dL/gm.

15. The drug delivery system of claim 10, wherein the microspheres have an average diameter between about 8 microns and about 14 microns.

16. The drug delivery system of claim 10, wherein the microspheres can release between about 0.5 μ

g/day to about 20 μ

g/day of the alpha 2 adrenergic agonist over a period of time of between about 10 days and about 100 days.

17. A biocompatible, injectable intraocular drug delivery system comprising:

(a) a plurality of microspheres with an average diameter between about 8 microns and about 14 microns, and

(b) an aqueous vehicle for the microspheres,

wherein the microspheres consist essentially of;

(1) a brimonidine, wherein the brimonidine comprises from about 0.5 wt % to about 15 wt % of the microspheres, and;

(2) one or more biodegradable polymers, all of which biodegradable polymers are poly(D,L)lactide polymers with an inherent viscosity of between about 0.4 dL/gm and about 0.8 dL/gm, wherein the PLA polymer comprises from about 85 wt % to about 99.5 wt % of the microspheres, and;

wherein the drug delivery system can be injected into an intraocular location through a 20 to 26 gauge syringe needle and the microspheres can release between about 0.5 μ

g/day to about 20 μ

g/day of the brimonidine a period of time of between about 10 days and about 100 days.

18. A method for treating an ocular condition, the method comprising the steps of:

(a) preparing a biocompatible drug delivery system comprising a plurality of microspheres, and an aqueous vehicle for the microspheres,

wherein the microspheres consist essentially of a therapeutic agent which is a brimonidine, and one or more biodegradable polymers, all of which biodegradable polymers are polylactic acid (PLA) polymers, and;

(b) injecting the drug delivery system into an intraocular location through a 20 to 26 gauge syringe needle, thereby treating an ocular condition, wherein the method does not result in significant ocular surface hyperemia.

20. A method for treating an ocular condition, the method comprising the steps of:

(a) preparing a biocompatible drug delivery system comprising an implant which consists essentially of an alpha 2 adrenergic agonist, and one or more biodegradable polymers, all of which biodegradable polymers are polylactic acid (PLA) polymers or polyortho esters, and;

(b) implanting the drug delivery system into an intraocular location thereby treating an ocular condition, wherein the method does not result in significant ocular surface hyperemia.

21. The method of claim 20, wherein the intraocular location is a sub-Tenon, subconjunctival, suprachoroidal, intrascleral or retrobulbar intraocular location.

22. A method for treating an ocular condition, the method comprising the steps of:

(a) preparing a biocompatible drug delivery system comprising an implant which consist essentially of a prostaglandin analog and one or more biodegradable polymers, all of which biodegradable polymers are polylactic acid (PLA) polymers or polyortho esters, and;

(b) implanting the drug delivery system into an intraocular location thereby treating an ocular condition, wherein the method does not result in significant ocular surface hyperemia.

23. A method for treating an ocular condition, the method comprising the steps of:

(a) preparing a biocompatible drug delivery system comprising an implant which consists essentially of an alpha 2 adrenergic agonist, and one or more biodegradable polylactic acid (PLA) polymers, and;

(b) implanting the drug delivery system into an intravitreal location thereby treating an ocular condition.

24. The method of claim 23, wherein the alpha 2 adrenergic agonist is a brimonidine tartrate.

25. A method for lowering intraocular pressure, the method comprising the steps of:

(a) preparing a biocompatible drug delivery system comprising an implant which consists essentially of a brimonidine tartrate, and one or more biodegradable polylactic acid (PLA) polymers, and;

(b) implanting the drug delivery system into an anterior sub-Tenon'"'"'s space, thereby lowering intraocular pressure.