Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1999-10-22
2001-12-18
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S422000, C424S424000, C424S423000, C424S428000, C604S891100
Reexamination Certificate
active
06331313
ABSTRACT:
TECHNICAL FIELD
The present invention relates to biocompatible controlled-release drug delivery devices that are implantable in the eye. Accordingly, the invention transcends the scientific disciplines of pharmaceutical delivery, polymer chemistry, and medicine.
BACKGROUND ART
A leading cause of blindness is the inability to introduce drugs or therapeutic agents into the eye and maintain these drugs or agents at a therapeutically effective concentration therein for the necessary duration. Systemic administration may not be an ideal solution because, often, unacceptably high levels of systemic dosing is needed to achieve effective intraocular concentrations, with the increased incidence of unacceptable side effects of the drugs. Simple ocular instillation or application is not an acceptable alternative in many cases because the drug may be quickly washed out by tear-action or is depleted from within the eye into the general circulation.
A better solution would be to provide a delivery device which can be implanted into the eye such that a controlled amount of desired drug can be released constantly over a period of several days, or weeks, or even months. Some such devices have been reported in the prior art. See, for example, U.S. Pat. No. 4,853,224, which discloses biocompatible implants for introduction into an anterior segment or posterior segment of an eye for the treatment of an ocular condition. U.S. Pat. No. 5,164,188 discloses a method of treating an ocular condition by introduction of a biodegradable implant comprising drugs of interest into the suprachoroidal space or pars plana of the eye. See also U.S. Pat. Nos. 5,824,072, 5,476,511, 4,997,652, 4,959,217, 4,668,506, and 4,144,317.
Many of the above-disclosed devices comprise of multiple layers and are complicated in their design and manufacture. Moreover, some of the devices are osmotically driven wherein an osmotic gradient is responsible for the drug efflux from the device. In some cases, the drug release is controlled by an ionic gradient. These devices thus must necessarily comprise these additional osmotic or ionic agents, which may not be compatible with the ocular environment. Thus, there is a need for a biocompatible ocular implantable controlled release drug delivery device that is simple in design, does not require an osmotic or ionic agent for drug efflux and yet accomplishes the objectives of prolonged and uninterrupted ocular drug delivery. This invention meets this need.
DISCLOSURE OF THE INVENTION
A biocompatible implantable ocular controlled release drug delivery device comprising a substantially impermeable polymeric outer layer covering a core which comprises the drug to be delivered, wherein said outer layer has one or more orifices, and said orifices in total having a surface area of less than 10 percent of the total surface area of said device.
The outer layer of the devices of this invention can be made biodegradable.
The devices of this invention can be used to deliver an antibiotic, an antiviral agent, an anti-fungal agent, an anticancer agent, an antiglaucoma agent, an antiinflammatory agent, an analgesic, an immunomodulatory agent, a macromolecule or a mixture thereof.
The present invention provides a biocompatible implantable ocular controlled release drug delivery device as described above wherein the outer layer comprises polytetrafluoroethylene, the core comprises gentamicin, cefazolin, or a mixture thereof, and the total area of orifices is less than 1 percent of the total surface area of the device.
The outer layer of the biocompatible implantable ocular controlled release drug delivery device as described above comprises polyfluorinated ethylenepropylene, and the core comprises dexamethasone, and the total area of orifices is less than 7 percent of the total surface area of the device.
The outer layer of the biocompatible implantable ocular controlled release drug delivery device described above comprises polytetrafluoroethylene, and the core comprises aldose reductase inhibitor, and the total area of orifices is less than 8 percent of the total surface area of the device.
Also provided is a biocompatible implantable ocular controlled release drug delivery device as described above wherein the outer layer comprises polytetrafluoroethylene, or silicone or a mixture thereof, the core comprises ganciclovir[9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]-methyl]-guanine], and the total area of orifices is less than 1 percent of the total surface area of the device.
Also provided is a biocompatible implantable ocular controlled release drug delivery device as described above wherein the outer layer comprises polylactic acid, polyglycolic acid, or a mixture thereof, the core comprises ganciclovir[9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]-methyl]-guanine], and the the total area of orifices is less than 1 percent of the total surface area of the device.
Methods are also provided for administering the biocompatible implantable ocular controlled release drug delivery device.
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Berger, Jr. Donald E.
Hu Mae W. L.
Wong Vernon G.
Di Nola-Baron Liliana
Morrison & Foerster / LLP
Oculex Pharmaceticals, Inc.
Page Thurman K.
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