Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
  • A61F2/02—Prostheses implantable into the body
  • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
  • A61F2/06—Blood vessels
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/08—Vasodilators for multiple indications
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
  • A61F2210/0095—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof radioactive

Definitions

• the present invention relates generally to the field of medical devices, and more particularly, to devices and methods to avoid vascular restenosis.
• stents have been used by physicians to prevent restenosis of blood vessels following treatments to expand vessels narrowed by arteriosclerosis. Following angioplasty to correct arteriosclerosis restenosis often occurs because such treatments stimulate excess tissue proliferation.
• Another solution to the problem of narrowed vessels is to surgically bypass them with a prostheses.
• Polytetrafiuoroethylene (PTFE) has proven advantageous as a material from which to fabricate blood vessel grafts or prostheses. This is partially because PTFE is extremely biocompatible causing little or no immunogenic reaction when placed within the human body. This is also because in its preferred form, expanded PTFE (ePTFE), the material is light and porous and can be readily colonized by living cells so that it becomes a permanent part of the body.
• vascular grafts Unfortunately, the process of suturing such a prosthesis of a living vessel often stimulates cellular proliferation similar to angioplasty.
• the failure modes of vascular grafts are frequently related to a luminal hyper-proliferative cellular response that eventually affects the flow dynamics resulting in thrombotic events and occlusion of blood flow.
• Dialysis access grafts typically fail at the venous anastomotic site due to flow related intimal hyperplasia.
• Peripherally placed bypass grafts often fail due to intimal thickening at the suture sites.
• ionizing radiation is capable of reducing restenosis and preventing cellular proliferation in vascular applications.
• the concept of Vascular Brachytherapy is relatively new.
• radiation has been used for years in Oncology, its use for the reduction of smooth muscle cell proliferation and the reduction of restenosis in vascular applications is recent.
• Ionizing radiation has the ability to damage cellular DNA and can either prevent the cells from dividing or can kill them outright.
• the utilization of a radiation source in vascular graft especially if incorporated into ePTFE, may have the ability to maintain graft patency for longer periods of time by preventing the hyper-proliferative responses mentioned above.
• a major problem with some current methods of treating restenosis through radiation therapy is that the radiation source is present as a fluid within the vascular lumen, such that the possibility of leakage is present, potentially causing major injury to the patient.
• U.S. Patent No. 5,616,114 to Thorton et al. discloses an apparatus and method to deliver radiation to the walls of a blood vessel through the use of a catheter with a balloon tip which balloon can be inflated with radioactive liquid. It would be desirable to provide radioactive therapy to areas of the body without the risk of causing injury to the patient in the event of a leak caused by balloon breakage.
• Other methods of using radiation to treat restenosis employ radioactive sources (often metallic) delivered by catheter.
• a difficulty with this approach is leaving the catheter in the patient's circulatory system for a long enough time to adequately affect restenosis.
• a radioactive source of adequate strength so as to minimize the indwelling time of the catheter may be so strong as to have a potential for overexposure and prove dangerous to work with.
• a source weak enough to avoid overexposure danger may result in problems caused by the lengthy indwelling of the delivery catheter.
• Yet another alternative is to place the radioactive sources on a metal stent. This approach may cause damage through direct contact between the radioactive stent and the vessel. Also, it may be difficult to achieve the desired pattern of radiation because the pattern is determined by the physical construction of the stent.
• the present invention is directed to radioactive grafts or cuffs, wherein radioactive therapy is localized to an afflicted area. This can be accomplished in several different ways by incorporating radioactive elements into vascular grafts or similar implantable medical devices.
• radioactive "seeds", coils, wires, fluids, etc. either encapsulated, impregnated, wrapped around or otherwise attached to a vascular graft, patch, drape or other implantable medical device.
• the material of construction could be ePTFE, polyester, silicon, polyurethane or any other biomedical material.
• the design of the device and choice of the radioisotope material dictates the duration and strength of the radioactivity.
• the biomedical material envelopes and encapsulates the radioactive source preventing accidental release and providing a "spacer" between the source and the cellular tissue to be treated.
• a first embodiment includes incorporating radioactive "seeds" (grains, granules, encapsulated radioactive fluid or other radioactive particles) into a graft either along its length or at proximal and distal ends.
• the seeds can be placed into the ePTFE or other biomedical material prior to extrusion (e.g., coextruded) or fabrication so that they will be embedded into the graft and will have an even distribution within the graft.
• a second embodiment uses radioactive seeds implanted in the biomedical material as in the first embodiment, but the end product is in the form of a "bandage" that is wrapped around a synthetic or natural vessel, irradiating the vessel to inhibit the tissue proliferation.
• a third embodiment incorporates radioactive wire into a graft by coiling the wire along its length or at isolated positions (e.g., near the point of anastamosis with the living vasculature). In the case of woven biomedical materials (e.g., polyester) the wire can be cowoven with the biomedical material.
• the radioactive "wire” can actually be a beading of solid plastic (e.g., PTFE) which contains radioactive powder or seeds.
• a fourth embodiment includes impregnating radioactive agents into the wall of a graft.
• a fifth embodiment utilizes an encapsulated stent graft with pockets that are filled with radioactive material. This embodiment can be used intraluminally or as an interposition graft.
• Fig. 1 is a perspective view of a first embodiment of the present invention with radioactive seeds dispersed throughout a graft
• Fig. 2 is a cut-away view of a second embodiment of the present invention with the radioactive seeds of Fig. 1 dispersed throughout a cuff-like device;
• Fig. 3 is a perspective view of a third embodiment of the present invention with a radioactive coil (wire or beading) wrapped around a graft;
• Fig. 4 is a perspective view of a fourth embodiment of the present invention with pockets of radioactive fluid dispersed throughout a graft
• Fig. 5 is a diagrammatic cross-sectional view of a mandrel and die assembly which is used to extrude a graft (especially PTFE) containing radioactive agents.
• the present invention satisfies the need for a medical device to prevent restenosis through radioactive elements incorporated therein.
• This can be accomplished by mixing the radioactive seeds or powders into PTFE or other biomedical material before extrusion of the device so that the radioactive elements are evenly distributed throughout the resulting graft or cuff.
• Another method of incorporation is to wrap a solid radioactive element (wire or beading) around the device during manufacture or just prior to implanting into the body.
• the various devices can be fabricated with a non-radioactive component that is then rendered radioactive by neutron bombardment prior to use. This allows device manufacture without need to worry about radioactive contamination of the site or workers.
• neutron bombardment can be used to generate radioactive isotopes with such short half-lives that normal manufacture and delivery would be impractical (that is, the radioactivity would be significantly decayed by the time the device was delivered).
• Fig. 1 illustrates a first embodiment of a radioactive graft 10.
• the graft 10 is composed of a biomedical material (e.g., ePTFE) 14 with embedded radioactive seeds 12.
• the seeds 12 are either solid particles or radioactive fluid droplets
• the latter method of forming the radioactive seeds 12 would present various advantages with respect to manufacturability, safety and shelf life.
• the material is PTFE or a similar substance extrusion will be explained with reference to Fig. 5 below.
• the flexibility of the radioactive graft 10 enables it to be used in many applications such as on the inside or outside of a stent.
• the radioactive element in the form of seeds, the radioactive properties can be manipulated based on need. Thus, if a longer duration of treatment is necessary, a long life, low energy isotope can be utilized; conversely, if a shorter more intense treatment is desired, a different isotope can be employed.
• Radioactive cuff 20 includes a strip 24 made of any biomedical material, such as ePTFE that is nonabsorbable, with imbedded radioactive seeds 12. As shown in Fig. 2, the radioactive cuff 20 is wrapped around a body vessel 70 like a bandage, so that the radioactive seeds 12 irradiate the proliferating cells 72 within the vessel.
• This cuff 20 is extremely versatile and can be used in many different applications, including treatment of non- vascular malignancies such as those found in the synthetic replacement of a bile duct.
• radioactive cuff 20 can be utilized for nearly any tube or lumen in the body that is being occluded by a growth.
• the radioactive properties of the seeds 12 can be chosen based on the specific application of the device, although an isotope with a very long half life emitting relatively low energy radiation will normally be preferred.
• the ePTFE prevents direct contact between the vascular tissue and the radioactive source. Thickness of the ePTFE can be selected to provide the ideal spacing between the source and the tissue.
• Fig. 3 shows a third embodiment of the present invention.
• the graft structure 30 includes a graft or tubular member 34 with a radioactive wire 32 coiled radially around the outside surface, extending along its length. Beading as of PTFE containing radioactive material can be used in place of wire. Beading can be readily laminated to the graft as can wire clad in an appropriate plastic material. If the biomedical material is woven or knitted, the wire or beading can also be woven or knitted into the structure.
• the graft structure 30 can be used in conjunction with a stent in which the graft structure 30 is used to cover either a luminal or abluminal stent surface for insertion into a body lumen.
• the radioactive wire 32 would then act to reduce the possibility of restenosis after the stent was deployed by eliminating the proliferating cells. Most likely the radioactive wire or beading would be limited to the end regions of the graft 34 where it is sutured to the patient's vasculature.
• the radioactive wire 32 can be attached to the graft with adhesives.
• the wire can be coated with PTFE (e.g., by inserting the wire 32 into an elongate PTFE tube of a slightly greater diameter than the wire 32) or other plastic. This coated wire can then be adhered to the graft 34 through heat and pressure or through the use of an adhesive.
• Fig. 4 illustrates a fourth embodiment of the present invention.
• the radioactive agent is again incorporated into an ePTFE or other biomedical material member.
• the radioactive substance is in the form of a liquid wherein a radioactive solution is prepared and small droplets of the solution are encased by tiny plastic shells.
• the resulting radioactive balls 42 are co-extruded with the biomedical material, creating a radioactive graft 40 containing small pockets 46 filled with radioactive balls 42.
• the graft 40 can also be created by implanting or encapsulating the radioactive balls 42 after graft fabrication.
• a fifth embodiment much like the first and third embodiments, radioactive or radiopharmaceutical agents are impregnated directly into the wall of an ePTFE graft without being aggregated as "seeds".
• the radioactive agent can come in the form of a ground up solid or powder which is coextruded with the PTFE.
• Fig. 5 illustrates a ram extruder assembly 50 for co-extruding a billet of material, which in this case consists of PTFE mixed with any of the radioactive agents described.
• the ram extruder assembly 50 includes an extrusion barrel 52, an extrusion die 54, a mandrel 56, and a ram 58.
• the billet of material 59 is placed within the extrusion barrel 52. Force is applied to ram 58 which in turn expels pressure on the billet of material 59. The pressure causes the billet of material 59 to be extruded around the mandrel 56, through the extrusion die 54 so that it issues as a tubular extrudate 60. An arrow 82 shows the direction of the extrusion.
• the tubular extrudate 60 is then expanded and sintered in accordance with the expansion and sintering procedures undertaken with pure PTFE vascular grafts which are well known in the art. Where plastic encased radioactive liquid ball 42 are used, encapsulation materials are selected so that the extrusion process does not result in rupture of the balls 42 and release of radioactive liquid.

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• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Heart & Thoracic Surgery (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Cardiology (AREA)
• Animal Behavior & Ethology (AREA)
• Transplantation (AREA)
• General Chemical & Material Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Gastroenterology & Hepatology (AREA)
• Biomedical Technology (AREA)
• Pulmonology (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Vascular Medicine (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Prostheses (AREA)
• Radiation-Therapy Devices (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Priority Applications (4)

Applications Claiming Priority (2)

Publications (2)

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Citations (4)

• 2000
  • 2000-09-21 JP JP2001524536A patent/JP2003509156A/ja active Pending
  • 2000-09-21 WO PCT/US2000/026111 patent/WO2001021106A1/en not_active Application Discontinuation
  • 2000-09-21 CA CA002381815A patent/CA2381815A1/en not_active Abandoned
  • 2000-09-21 EP EP00965347A patent/EP1214019A1/en not_active Withdrawn
  • 2000-09-21 MX MXPA02003066A patent/MXPA02003066A/es unknown

Patent Citations (4)

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