Modulation of cell proliferation and wound healing

• US 6,063,116 A
• Filed: 06/27/1997
• Issued: 05/16/2000
• Est. Priority Date: 10/26/1994
• Status: Expired due to Fees

• Current Assignee: Medarex Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Medarex Incorporated (Bristol-Myers Squibb Company)
• Inventors: Kelleher, Peter J.
• Primary Examiner(s): Milano, Michael J.
• Assistant Examiner(s): Nguyen, Dinh X.
• Application Number:
  US08/836,899
• Time in Patent Office: 1,054 Days
• Field of Search: 623/4, 623/5, 623/6, 623/11, 623/66, 128/898, 424/422, 424/423, 424/424, 424/426, 424/427, 424/428, 424/429, 514/912
• US Class Current: 623/6.56
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Intraocular devices which are capable of sustained release of a cell proliferation modulating agent, together with methods for their preparation and use, are provided. The proliferation modulating agent is associated either covalently or non-covalently with the material from which the intraocular device is prepared, generally a biologically inert polymer which is physiologically compatible with ocular tissue. The intraocular devices are implanted in the tissue, and the drug is released from the intraocular device such that the drug is substantially retained within the implant region. The device may be used to inhibit cellular proliferation around the implant. The device can be provided as a sterile kit, preferably in a form suitable for immediate use.

Claims

1. An occular implant comprising:

a biologically inert polymer having at least one proliferation inhibiting agent associated therewith by a labile interaction selected from the group consisting of;

a hydrophobic interaction and a hydrophilic interaction, such that upon implantation into the eye said proliferation inhibiting agent is gradually released from the implant in a localized region of the eye to thereby inhibit proliferation of target cells in the localized region of the eye.

3. The implant according to claim 1, wherein the polymer is selected from the group consisting of polyamides, polypeptides, polyesters, polycarbonates, polyurethanes, polyacetals, polysaccharides, and polyolefins.

4. The implant according to claim 1, wherein the polymer is selected from the group consisting of silicone rubber, polyurethane rubber, polyethylene, polyvinyl chloride, poly(hydroxyethyl methacrylate), poly(methyl methacrylate), poly(ethyleneterephthalate), polypropylene, polystryene, poly(tetrafluoroethylene), polyglycolic acid, cellulose, ethylcellulose, methycellulose, dextran, carboxymethylcellulose, hyaluronic acid, nylon, and collagen.

5. The implant according to claim 1, wherein the polymer is a polysaccharide selected from the group consisting of:

carboxymethylcellulose, hyaluronic acid, and heparin.

6. The implant according to claim 1, wherein the proliferation inhibiting agent is selected from the group consisting of:

doxirubicin, daunomycin, and 5-fluorouracil.

7. The implant according to claim 1, wherein said inhibiting agent is a toxin.

8. The implant according to claim 7, wherein said toxin is ricin.

9. The implant according to claim 1, wherein said implant is a membrane.

10. The implant according to claim 1, wherein said implant is selected from the group consisting of an intraocular lens, drainage shunt, a prosthesis, and a lens capsular loop.

11. The implant according to claim 1, wherein said polymer is selected from the group consisting of silicon, polymetthylmethacrylate, and nylon.

12. The implant according to claim 1, wherein the polymer is nylon and said proliferation inhibiting agent is daunomycin.

13. A method for killing residual lens epithelial cells after cataract surgery, said method comprising placing an implant according to claim 1 into an eye during or after said cataract surgery, to thereby kill residual lens epithelial cells.

14. A method for preventing formation of scar tissue in an eye, said method comprising placing an implant according to claim 1 into a fistula, whereby scar formation is prevented.

2. An occular implant comprising:

a biologically inert polymer having at least one proliferation inhibiting agent associated therewith by a labile covalent bond selected from the group consisting of;

a hydrazone bond and a semicarbazone bond, such that upon implantation into the eye said proliferation inhibiting agent is gradually released from the implant in a localized region of the eye to thereby inhibit proliferation of target cells in the localized region of the eye.

15. A method for preparing an intraocular device, said method comprising:

contacting a biologically inert polymer with a proliferation inhibiting agent, such that a labile interaction selected from the group consisting of;

hydrazone bond, a semicarbazone bond, a hydrophobic interaction, and a hydrophilic interaction between said polymer and said proliferation inhibiting agent results.