Claims for Patent: 5,378,475

Summary for Patent: 5,378,475

Title:	Sustained release drug delivery devices
Abstract:	A method and device for treating a mammalian organism to obtain a desired local or systemic physiological or pharmacological effect is provided. The method includes administering a sustained release drug delivery system to a mammalian organism in need of such treatment at an area wherein release of an effective agent is desired and allowing the effective agent to pass through the device in a controlled manner. The device includes an inner core or reservoir comprising the effective agent; a first coating layer, which is essentially impermeable to the passage of the effective agent; and a second coating layer, which is permeable to the passage of the effective agent. The first coating layer covers at least a portion of the inner core; however, at least a small portion of the inner core is not coated with the first coating layer. The second coating layer essentially completely covers the first coating layer and the uncoated portion of the inner core.
Inventor(s):	Smith; Thomas J. (Boston, MA), Ashton; Paul (Lexington, KY), Pearson; Paul A. (Lexington, KY)
Assignee:	University of Kentucky Research Foundation (Lexington, KY)
Application Number:	07/658,695
Patent Claims:	1. A method for treating a mammalian organism to obtain a desired local or systemic physiological or pharmacological effect comprising: administering a sustained release drug delivery system to a mammalian organism in need of such treatment, said drug delivery system comprising; (1) an inner core or reservoir comprising an effective amount of an agent to obtain a desired local or systemic physiological or pharmacological effect, (2) a first polymer coating layer, said first coating layer essentially impermeable to the passage of said agent, and said first polymer coating layer covering at least a portion of the inner core, wherein at least a small portion of the inner core is not coated with said first coating layer, and (3) a second polymer coating layer permeable to the passage of said agent, wherein said second polymer coating layer essentially completely covers said first polymer coating layer and the uncoated portion of the inner core, whereby said agent is able to pass through said second polymer coating layer in a controlled manner wherein said first polymer coating layer and said second polymer coating layer are essentially insoluble and inert in body fluids. 2. A method for treating a mammalian organism as claimed in claim 1, wherein said second coating layer comprises polyvinyl alcohol. 3. A method for treating a mammalian organism as claimed in claim 2, wherein said first coating layer comprises ethylene vinyl acetate. 4. A method for treating a mammalian organism as claimed in claim 3, wherein said effective agent comprises 5-fluorouracil or ganciclovir. 5. A method for treating a mammalian organism for cytomegalovirus retinitis comprising: administering a sustained release drug delivery system to a mammalian organism in need of such treatment, said drug delivery system comprising; (1) an inner core or reservoir comprising an effective amount of ganciclovir effective to obtain a desired local or systemic physiological or pharmacological effect, (2) a first polymer coating layer, said first polymer coating layer essentially impermeable to the passage of said ganciclovir, and said first polymer coating layer covering at least a portion of the inner core, wherein at least a small portion of the inner core is not coated with said first polymer coating layer, and (3) a second polymer coating layer permeable to the passage of said ganciclovir, wherein said second polymer coating layer essentially completely covers said first polymer coating layer and the uncoated portion of the inner core, whereby said ganciclovir is able to pass through said second polymer coating layer in a controlled manner. 6. A method for treating a mammalian organism to obtain a desired physiological or pharmacological effect comprising: placing a sustained release drug delivery system in contact with or within an eye of a mammalian organism in need of such treatment, said drug delivery system comprising; (1) an inner core having an effective amount of an agent to obtain a desired local or systemic physiological or pharmacological effect and an inner polymer coating permeable to the passage of said agent covering at least a portion of said agent, (2) a first polymer coating essentially impermeable to the passage of said agent, said first polymer coating covering at least a portion but not the entire surface area of said inner polymer coating of said inner core, and (3) a second polymer coating permeable to the passage of said agent, wherein said second polymer coating essentially completely covers said first polymer coating and any uncoated portion of the inner core, whereby said agent is able to pass through said second polymer coating, wherein each of the polymers selected to make the device are essentially insoluble and inert in body fluids and compatible with eye tissues, and allowing said agent to pass through said second polymer coating to obtain a desired effect. 7. The method for treating a mammalian organism according to claim 6, wherein said inner coating of said inner core comprises polyvinyl alcohol. 8. The method for treating a mammalian organism according to claim 6, wherein said first coating comprises ethylene vinyl acetate. 9. The method for treating a mammalian organism according to claim 6, wherein said second coating comprises polyvinyl alcohol. 10. The method for treating a mammalian organism according to claim 6, wherein said agent is ganciclovir or 5-fluorouracil. 11. The method for treating a mammalian organism according to claim 6, wherein said inner coating of said inner core comprises polyvinyl alcohol, said first coating comprises ethylene vinyl acetate, said second coating comprises polyvinyl alcohol and said agent is cyclosporin, dexamethasone, 5-fluorouracil or ganciclovir. 12. A sustained release drug delivery system suitable for placing in contact with or within the eye to provide a desired physiological or pharmacological effect comprising: (1) an inner core having an effective amount of an agent to obtain a desired local or systemic physiological or pharmacological effect and an inner polymer coating permeable to the passage of said agent covering at least a portion of said agent, (2) a first polymer coating essentially impermeable to the passage of said agent, said first polymer coating covering at least a portion but not the entire surface area of said inner polymer coating of said inner core, and (3) a second polymer coating permeable to the passage of said agent, wherein said second polymer coating essentially completely covers said first polymer coating and any uncoated portion of the inner core, wherein each of the polymers selected to make the device are essentially insoluble and inert in body fluids and compatible with eye tissues. 13. The sustained release drug delivery system suitable for placing in the eye according to claim 12, wherein said inner coating of said inner core comprises polyvinyl alcohol. 14. The sustained release drug delivery system suitable for placing in the eye according to claim 12, wherein said first coating comprises ethylene vinyl acetate. 15. The sustained release drug delivery system suitable for placing in the eye according to claim 12, wherein said second coating comprises polyvinyl alcohol. 16. A method for providing controlled and sustained administration of an agent effective in obtaining a desired local or systemic physiological or pharmacological effect comprising: surgically implanting a sustained release drug delivery system at a desired location, said drug delivery system comprising; (1) an inner core or reservoir comprising an effective amount of an agent effective in obtaining a desired physiological or pharmacological effect, (2) a polymer coating layer which is essentially impermeable to the passage of said effective .mu.gent, said impermeable layer covering at least a portion or the inner core, wherein at least a small portion of the inner core is not coated with said impermeable polymer coating layer, and (3) a polymer coating layer which essentially completely covers the inner core and is permeable to the passage of said effective agent whereby said agent is able to pass through said polymer coating layer in a controlled manner. 17. A method as claimed in claim 16, wherein said device is surgically implanted within the vitreous of the eye. 18. The sustained release drug delivery system suitable for placing in the eye according to claim 12, wherein said agent is cyclosporin, dexamethasone, 5-fluorouracil or ganciclovir. 19. A method as claimed in claim 17, wherein said permeable coating layer comprises polyvinyl alcohol. 20. A method as claimed in claim 18, wherein said impermeable coating layer comprises ethylene vinyl acetate. 21. A method as claimed in claim 20, wherein said effective agent is ganciclovir or 5-fluorouracil. 22. A sustained release drug delivery system comprising: (A) an inner core or reservoir comprising an effective amount of an agent effective in obtaining a desired local or systemic physiological or pharmacological effect, (B) a first polymer coating layer, said first polymer coating layer impermeable to the passage of said effective agent, and said first polymer coating layer covering at least a portion of the inner core, wherein at least a small portion of the inner core is not coated with said first polymer coating layer, and (C) a second polymer coating layer, said second polymer coating layer permeable to the passage of said effective agent, wherein said second polymer coating layer essentially completely covers the first polymer coating layer and the uncovered portion of the inner core, said first polymer coating layer and said second polymer coating layer being essentially insoluble and inert in body fluids. 23. A sustained release drug delivery system as claimed in claim 22, wherein said second coating layer comprises polyvinyl alcohol. 24. A sustained release drug delivery system as claimed in claim 23, wherein said first coating layer comprises ethylene vinyl acetate. 25. A sustained release drug delivery system as claimed in claim 24, wherein said effective agent is ganciclovir or 5-fluorouracil. 26. The method for treating a mammalian organism as claimed in claim 1, wherein said drug delivery system is attached to an intraocular lens or the haptic extending from said intraocular lens. 27. The sustained release drug delivery system suitable for placing in the eye according to claim 12, wherein said inner coating of said inner core comprises polyvinyl alcohol, said first coating comprises ethylene vinyl acetate, said second coating comprises polyvinyl alcohol and said agent is ganciclovir or 5-fluorouracil. 28. The sustained release drug delivery system according to claim 22, further comprising a polymeric layer between said inner core or reservoir and said impermeable coating, whereby said agent is able to pass through said polymeric layer 29. A sustained release drug delivery system comprising: (a) in inner core or reservoir comprising an effective amount of an agent effective in obtaining a desired local or systemic physiological or pharmacological effect, (b) a first polymer coating layer, said first polymer coating layer impermeable to the passage of said effective agent, and said first polymer coating layer covering at least a portion of the inner core, wherein at least a small portion of the inner core is not coated with said first polymer coating layer, and (c) a second polymer coating layer, said second polymer coating layer permeable to the passage of said effective agent, wherein said second polymer coating layer essentially completely covers the first polymer coating layer and the uncovered portion of the inner core, wherein said sustained drug delivery system is attached to an intraocular lens or the haptic extending from said intraocular lens. 30. The sustained drug release delivery system as claimed in claim 29, wherein said effective agent is ganciclovir, 5-fluorouracil, colchicine or dexamethasone. 31. The method for treating a mammalian organism according to claim 1, wherein said sustained release drug delivery system is placed in contact with or within an eye of said mammalian organism. 32. The method for treating a mammalian organism according to claim 1, wherein said sustained release drug delivery system further comprises a polymeric layer between said inner core or reservoir and said impermeable coating, whereby said agent is able to pass through said polymeric layer between said inner core or reservoir and said impermeable coating. 33. The method for treating a mammalian organism according to claim 22, wherein said core consists essentially of said agent or a pharmaceutically acceptable salt of said agent. 34. The method for treating a mammalian organism according to claim 1, wherein said core consists essentially of said agent or a pharmaceutically acceptable salt of said agent. 35. The sustained release drug delivery system according to claim 22, wherein said polymers used to fabricate said first and second layer are compatible with eye tissues. between said inner core or reservoir and said impermeable coating.