Modulation of cell proliferation and wound healing

Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Eye prosthesis

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623 5, 623 6, 424424, 424428, A61F 214, A61F 216

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060631163

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This invention relates to methods and compositions featuring polymer implants associated with cell proliferation modulating agents. The invention provides for the modulation of cell proliferation and/or wound healing at sites immediately adjacent to the implant and for the inhibition of cell adhesion to the implant itself.


BACKGROUND

The inappropriate proliferation of cells in an organism may lead to a variety of disease states. The particular symptoms will vary depending oil the type of proliferative cell and on the location of the cell. These disease states may range from cancerous malignancies when the cell is a cancer cell, to scarring when the cell type is a normal fibroblast, or to a skin disease when the proliferating cell is an epithelial or dermal cell forming a part of the integument or skin.
Proliferation of cells in various tissues of the eye can lead to impaired vision. One such example of impaired vision results from a proliferation of lens epithelial cells which remain associated with the lens capsule following cataract surgery. Specifically, extracapsular cataract extraction for the removal of cataracts frequently is accompanied by an undesired proliferation of lens epithelial cells, resulting in posterior lens capsule opacification. Virtually all pediatric patients and approximately 50% of adult patients undergoing extracapsular cataract extraction develop an opaque secondary cataract within three to five years of surgery.
Various cytotoxic agents are reported to inhibit secondary cataract formation or posterior lens capsule opacification. For example, cytotoxic agents such as 5-fluorouracil, methotrexate, colchicine, and daunomycin have been instilled into the anterior chamber of the eye to kill residual lens epithelial cells for prevention of posterior lens capsule opacification. These drugs have been delivered, e.g., by injection or with the aid of various drug delivery techniques that provide for diffusion of the drug within the eye.
A second example of vision-threatening cellular proliferation occurs following glaucoma surgery. Glaucoma encompasses a heterogeneous group of eye diseases characterized by a classical triad of symptoms: elevated intraocular pressure (IOP), optic nerve damage and progressive visual field loss. The increase in IOP is due to a decrease in the outflow of aqueous humor, the fluid in the anterior segment of the eye that is responsible for maintaining pressure balance for the entire eye. Current medical therapy for glaucoma involves the administration of one or more ocular agents, including beta-blockers (e.g., timolol), miotics (e.g., pilocarpine), adrenergic agonists (e.g., epinephrine) and carbonic anhydrase inhibitors (e.g., acetazolamide). While most glaucoma patients initially respond to drug therapy, many become refractory over time. For those individuals, maintenance of normal IOP requires surgical intervention.
Surgical techniques for the correction of glaucoma include various types of glaucoma filtering surgery (GFS), during which a drainage channel is created for aqueous humor outflow from the anterior chamber in order to lower IOP. The most successful GFS is that which uses the creation of a filtering bleb or drainage fistula, which is an elevation of the conjunctiva at the surgical site, to decrease IOP. Numerous techniques may be employed to maintain the patency of the bleb or fistula, including the use of biocompatible plastic tubes or valves, yet scarring over of the drainage channel frequently causes blockage of the bleb or fistula and a concomitant increase in IOP. Recent clinical studies have demonstrated that introduction of agents which inhibit the wound healing process can in some instances improve the success rate of GFS. These agents typically are administered by non-specific means such as application by sponge to the drainage filter tissue during the surgical procedure or by repeated, painful injections into the conjunctiva after the operation.
Drug delivery techniques which have been reported both for preventi

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