Ocular therapeutic agent delivery devices and methods for making and using such devices

• US 6,713,081 B2
• Filed: 03/15/2001
• Issued: 03/30/2004
• Est. Priority Date: 03/15/2001
• Status: Expired due to Term

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Inventors: Yuan, Peng, Robinson, Michael R., Smith, Janine A., Sung, Cynthia, Nussenblatt, Robert B., Csaky, Karl G.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): CHANNAVAJJALA, LAKSHMI SARADA
• Application Number:
  US09/808,149
• Publication Number:
  US 20030175324A1
• Time in Patent Office: 1,111 Days
• Field of Search: 424/422-427, 424/484, 424/485, 424/486, 424/487, 424/488, 424/78.04
• 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: A61F 9/00781 Apparatus for modifying intraocular pressure, e.g. for glaucoma treatment drainage implants in general A61M27/002
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: B29D 11/023 Implants for natural eyes
• CPC Class Codes: B29K 2083/00 Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as moulding material
• CPC Class Codes: B29K 2827/18 PTFE, i.e. polytetrafluorethene, e.g. ePTFE, i.e. expanded polytetrafluorethene
• CPC Class Codes: Y10S 425/808 Lens mold

Abstract

Ocular implant devices for the delivery of a therapeutic agent to an eye in a controlled and sustained manner. Dual mode and single mode drug delivery devices are illustrated and described. Implants suitable for subconjunctival placement are described. Implants suitable for intravitreal placement also are described. The invention also includes fabrication and implementation techniques associated with the unique ocular implant devices that are presented herein.

Claims

1. An ocular implant providing sustained-release of a first therapeutic agent to the eye for a prolonged period of time, comprising:

a composite material matrix layer including;

(i) a first therapeutic agent,

(ii) a polymeric matrix material into which the first therapeutic agent is dispersed, including (1) a bioerodible polymer permeable to the therapeutic agent, the permeable polymer being superhydrolyzed polyvinyl alcohol, and (2) a water-soluble polymer having greater water solubility than the permeable polymer, the water-soluble polymer being a cellulose ether polymer, and

(iii) a discrete solid core containing the first or a second therapeutic agent, the therapeutic agent being dispersed, and the solid core being embedded within the composite material matrix layer.

2. The implant according to claim 1, wherein the composite material matrix layer comprises about 5 to about 50 wt % of the permeable polymer, about 0.05 to about 90 wt % of the water-soluble polymer, and about 1.0 to about 50 wt % of the first therapeutic agent.

3. The implant according to claim 1, wherein the composite material matrix layer comprises about 5 to about 50 wt % of the superhydrolyzed polyvinyl alcohol, about 0.05 to about 90 wt % of the cellulose ether polymer, and about 1.0 to about 50 wt % of the first therapeutic agent.

4. The implant according to claim 1, wherein the cellulose ether polymer comprises hydroxyalkyl cellulose.

5. The implant according to claim 1, wherein the cellulose ether polymer comprises hydroxypropyl methyl cellulose.

6. The implant according to claim 1, wherein a part of the exterior surface area of the composite material matrix layer is covered by polymethyl methacrylate sufficient to adjust the rate of delivery of the therapeutic agent from the implant to the eye.

7. The implant according to claim 1, wherein the composite material matrix layer comprises about 5 to about 50 wt % superhydrolyzed polyvinyl alcohol.

8. The implant according to claim 1, wherein the therapeutic agent is selected from the group consisting of antibiotic agents, antibacterial agents, antiviral agents, anti-glaucoma agents, antiallergenic agents, anti-inflammatory agents, anti-angiogenesis compounds, antiproliferative agents, immune system modifying agents, anti-cancer agents, antisense agents, antimycotic agents, myotic agents, anticholinesterase agents, mydriatic agents, differentiation modulator agents, sympathomimetic agents, anaesthetic agents, vasoconstrictive agents, vasodillatory agents, decongestants, cell transport/mobility impending agents, polypeptides and protein agents, steroidal agents, carbonic anhydrase inhibitor agents, polycations, polyanions, lubricating agents, and mixtures thereof.

9. An ocular implant providing sustained-release of a therapeutic agent to the eye for a prolonged period of time, comprising:

(a) a composite material matrix layer including;

(i) a first therapeutic agent, and

(ii) a polymeric matrix material into which the first therapeutic agent is dispersed, including poly(ethylene vinyl) acetate and a cellulose ether polymer, and

(b) optionally, a discrete solid core containing an additional amount of the first therapeutic agent or a second different therapeutic agent, wherein said solid core being embedded within the composite material matrix layer.

10. A method of delivering a therapeutic agent to an eye in need of treatment thereof, comprising attaching an implant containing a therapeutic agent to the eye, wherein the implant comprises a composite material matrix layer including a therapeutic agent, and a polymeric matrix material into which the therapeutic agent is dispersed including a superhydrolyzed polyvinyl alcohol permeable to the therapeutic agent and a cellulose ether polymer, and, optionally, a discrete solid core containing additional therapeutic agent and embedded within the composite material matrix layer, effective to deliver the therapeutic agent to the eye.

11. The method of claim 10, wherein the implant is attached to a subconjunctival region of the eye.

12. The method of claim 10, wherein the implant is attached to an intravitreal region of the eye.

13. The method of claim 10, wherein the discrete solid core is included, and delivery of the therapeutic agent proceeds as an initial loading dose delivery followed by sustained release of a lower, relatively constant rate of infusion.

14. The method of claim 10, wherein the therapeutic agent in the composite material matrix layer and the discrete solid core comprises cyclosporine.

15. The method of claim 12, wherein the implant is attached to a subconjunctival region of the eye, and wherein therapeutic agent is delivered in an amount effective for corneal allograft therapy.

16. The method of claim 10, wherein the therapeutic agent in the composite material matrix layer and the pellet comprises 2-methoxyestradiol.

17. The method of claim 12, wherein the implant is attached to an intravitreal region of the eye, and wherein therapeutic agent is delivered in an amount effective for treatment of chordial neovascular membranes CNVM.

18. The method of claim 10, wherein treatment is performed on the eye of a mammalian organism.