Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2002-06-11
2004-12-28
Kishore, Gollamudi S. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S400000, C424S042000, C424S423000, C424S424000
Reexamination Certificate
active
06835387
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to implantable or insertable medical devices and more particularly to implantable or insertable medical devices comprising a polymer that releases a therapeutic agent.
2. Brief Description of the Background Art
Superoxide dismutase mimics are enzymes that catalyze dismutation of superoxide radicals (O
2
.
−
) by converting them to less reactive hydrogen peroxide (H
2
O
2
) and dioxygen (O
2
). The body's response to implanted biomedical materials typically involves inflammation to varying degrees. To address this inflammation, superoxide dismutase mimics have been covalently attached to the surfaces of various biomaterials for implantation. See Udipi, K. et al, “Modification of inflammatory response to implanted biomedical materials in vivo by surface bound superoxide dismutase mimics,”
J. Biomed. Mater. Res
. Sep. 15, 2000; 51(4):549-60.
Local delivery of therapeutic agents from implantable or insertable medical devices is an important new technology in the treatment of diseases.
For example, intraluminal stents are commonly inserted into the coronary artery after percutaneous transluminal coronary angioplasty procedures. Such stents are provided to maintain the patency of the coronary artery by supporting the arterial walls and preventing abrupt reclosure or collapse thereof, which can occur after the angioplasty procedure. However, the presence of a stent can exacerbate restenosis of the vessel.
In response to this problem, local delivery of a number of restenosis-inhibiting therapeutic agents (such as paclitaxel, rapamycin, nitric oxide donors, and so forth) from coatings of stents that have been inserted after percutaneous transluminal coronary angioplasty procedures has been proposed.
However, the technology associated with drug delivery from coated vascular medical devices such as coronary stents is a relatively new one. Moreover, while numerous therapeutic agents have been proposed as noted above, it is possible that certain of these agents will ultimately be found to act on an inappropriate cell physiology, or that they are not be presented to the vasculature in appropriate concentrations.
SUMMARY OF THE INVENTION
In accordance with the present invention, an implantable or insertable medical device, for example, a vascular stent, is provided which comprises (a) a superoxide dismutase mimic and (b) a polymeric release region. Upon administration to a patient, the polymeric release region controls the release of the superoxide dismutase mimic, which is beneficially selected from a metal-chelate superoxide dismutase mimic and a nitroxide superoxide dismutase mimic.
Examples of implantable or insertable medical devices appropriate for the practice of the present invention, besides vascular stents, include catheters, balloons, cerebral aneurysm filler coils and arterio-venous shunts as well as non-vascular stents such as biliary stents and renal stents.
In some embodiments, the superoxide dismutase mimic is a nitroxide compound, for example, 2,2,6,6-tetramethylpiperidine-1-yloxy, 4-hydroxytetramethyl-piperidine-1-oxyl or 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-N-oxyl. In other embodiments, the superoxide dismutase mimic is a metal-chelate compound, for example, a metal-pentaazacyclopentadecane compound, a metal-porphyrin compound, a metal-porphine compound, a metal-desferioxamine compound, a metal-bis(cyclohexylpyridine) compound or a salen-metal compound.
Typically, the polymeric release region is either a polymeric matrix within which the superoxide dismutase mimic is disposed, or a polymeric barrier layer that is disposed over the superoxide dismutase mimic. Numerous polymers can be used in the construction of the polymeric release region. One particularly preferred group of polymers are copolymers of isobutylene and styrene.
The medical devices of the present invention can be administered in the treatment of a number of diseases and conditions, including restenosis, gastrointestinal inflammation, and inflammatory processes involving the vasculature or other lumens within the body (e.g., duct inflammation).
The release profile associated with the devices of the present invention can be tailored to the treatment of interest. In some embodiments, the release profile is an extended release profile in which less than 50% of the total amount of superoxide dismutase mimic that is released into the vasculature from the medical device is released within the first 24 hours of administration.
According to further embodiments of the present invention, a method of forming an implantable or insertable medical device is provided. The method comprises: (a) providing a solution or dispersion comprising (i) a superoxide dismutase mimic selected from a metal-chelate superoxide dismutase mimic and a nitroxide superoxide dismutase mimic, (ii) a polymer and (iii) a solvent; (b) contacting the solution or dispersion with a medical device; and (c) removing the solvent to form a superoxide dismutase mimic-containing polymer matrix on the medical device. The solution or dispersion can be contacted with the medical device in a number of ways, including spraying the medical device with the solution or dispersion, or dipping the medical device in the solution or dispersion.
One advantage of the present invention is that implantable or insertable medical devices are provided, which enable the extended release of superoxide dismutase mimics from the device surface.
In contrast to prior art implantable biomedical materials in which superoxide dismutase mimics are covalently attached at the surface, the medical devices of the present invention are also advantageous at least in that: (1) the superoxide dismutase mimics are released to surrounding tissue, allowing the surrounding material to be treated, and (2) the amount of superoxide dismutase mimic provided can be an order of magnitude greater than that provided by surface attachment techniques.
A further advantage of the present invention is that treatment methods, including a method for the treatment of restenosis, are provided, which utilize the above medical devices.
In connection with the controlled release aspects of the devices of the present invention, yet another advantage is that a subject can be treated without significant risk of local overdose.
Still another advantage of the present invention is that, due to the catalytic nature of superoxide dismutase mimics, side effects are expected to be minimal.
These and other embodiments and advantages of the present invention will readily become apparent to those of ordinary skill in the art upon review of the Detailed Description and claims to follow.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with various embodiments of the invention, implantable or insertable medical devices are provided that comprise a polymer release region for a superoxide dismutase mimic. Typically, the superoxide dismutase mimic is (a) disposed within the polymer release region, in which case the polymer release region may be referred to herein as a polymer matrix, or (b) disposed beneath the polymer release region, in which case the polymer release region may be referred to herein as a polymer barrier layer. As a result of the polymer release region, at least a portion of the superoxide dismutase mimic within the medical device is released upon administering the medical device to the vasculature a patient.
Diseases and conditions that are treated using the medical devices of the present invention include restenosis, gastrointestinal inflammation, and inflammatory processes involving the vasculature or other lumens within the body (e.g., duct inflammation). As used herein, “treatment” refers the prevention of a disease or condition, the reduction or elimination of symptoms associated with a disease or condition, or the substantial or complete elimination a disease or condition. Preferred subjects are vertebrate subjects, more preferably mammalian subjects and most preferably human subjects.
Superoxide dismutase mim
Bonham, Esq. David B.
Kishore Gollamudi S.
Mayer Fortkort & Williams PC
Oh Simon J.
Sci-Med Life Systems, Inc.
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