JP2003509156A - Radioactive graft or cuff - Google Patents

Abstract

(57) Abstract Radioactive grafts or cuffs are manufactured by incorporating a radioactive liquid into a flexible material such as expanded PTFE. A radioactive graft or cuff is placed in the body to prevent the growth of the deteriorated cells. For example, a graft or cuff can be used in a closed lumen after opening it to prevent restenosis from occurring later. Although grafts are primarily used for implantation inside body cavities, cuffs can be used in a variety of locations, for example, wrapped around diseased vessels. Some embodiments of the present invention incorporate a radioactive seed into the expanded PTFE graft. The radioisotopes in seed form are selected according to their radioactivity and mixed with PTFE before extrusion. After extrusion, the PTFE is foamed and sintered to form the final product.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD OF THE INVENTION

The present invention relates generally to the field of medical devices, and more particularly to devices and methods for preventing restenosis of blood vessels.

[0002]

[Prior art]

Many devices, such as stents, have been used by physicians to prevent restenosis of blood vessels from occurring after treatment to dilate narrowed blood vessels due to arteriosclerosis. Restenosis often occurs after angioplasty to correct arteriosclerosis. This is because such treatment stimulates excessive tissue growth.

Another solution to the problem of vessel stenosis is to surgically bypass the vessel with a prosthesis. Polytetrafluoroethylene (PTFE) has been found to be advantageous as a material for making vascular grafts or artificial blood vessels. This is because PTFE is extremely biocompatible and produces little or no immune response when placed in the human body. This is also because in its preferred form, namely expanded PTFE (ePTFE) form, the material is lightweight and porous, allowing living cells to easily form colonies and thus become a permanent member of the body. is there. Unfortunately, the process of suturing such prostheses to living blood vessels often stimulates cell proliferation, similar to angioplasty. Failure modes of vascular grafts are often associated with intraluminal hyperproliferative cell responses. This response ultimately affects the flow kinetics, results in thrombosis and blocks blood flow. Dialysis access grafts typically break at the venous anastomosis site. This is due to flow-associated intimal hyperplasia. Peripherally placed bypass grafts often fail due to thickening of the intimal vein at the suture site.

Clinical investigations have shown that ionizing radiation can reduce restenosis and block cell proliferation when applied to the vasculature. However, the concept of vascular brachytherapy is relatively new. Although radiation has been used in oncology for many years, it has only recently been used to reduce proliferation of smooth muscle cells and to reduce restenosis in vascular applications. Ionizing radiation has the power to damage the DNA of cells, either blocking cell division or killing these cells altogether. The use of radiation sources in vascular grafts, especially when incorporated into expanded PTFE,
By eliminating the hyperproliferative response described above, the patency of the graft can be maintained for a long period of time.

A major problem with some current methods of treating restenosis with radiation therapy is that the radiation source resides in the vascular lumen in a liquid state, which can result in leaks that can severely injure the patient. It means that there is a nature. For example, US Pat. No. 5,616,114 to Thorton et al. Discloses an apparatus and method for delivering radiation to a vessel wall by using a catheter having a balloon tip that can be inflated with a radioactive liquid. ing. It is desirable to administer radiation therapy to an area within the body without risking injury to the patient if the balloon ruptures and leaks occur.

[0006] Another method of using radiation to treat restenosis uses a catheter-delivered source of radiation, often metallic. The problem with this method is that it leaves the catheter in the patient's circulatory system for an extended period of time in order to have a proper effect on restenosis. It has been found that sources of radioactivity of adequate strength to minimize catheter dwell time are so strong and dangerous that there is a risk of overexposure.
Radioactive sources that are weak enough to eliminate the risk of overexposure suffer from the long dwell time of the delivered catheter. Yet another variation is to place the radioactive source on a metal stent. This method can cause damage due to direct contact between the radioactive stent and the blood vessel. Furthermore, it is difficult to obtain the desired radiation pattern because the pattern is determined by the physical structure of the stent.

The present invention relates to a radiation graft or cuff that provides radiation therapy only to the lesion area. This can be done in several different ways by incorporating the radioactive liquid into a vascular graft or similar implantable medical device.

[0008]

[Problems to be Solved by the Invention]

It is an object of the present invention to provide an implantable medical device that uses radiation therapy to prevent tissue overgrowth, especially due to restenosis of blood vessels.

Another object of the present invention is to provide a device for radiation therapy that does not carry the transport of radioactive fluids that can leak through the body.

[0010]

[Means for Solving the Problems]

These and additional purposes are by incorporating radioactive "seed", coils, wires, fluids, etc. into encapsulating, mixing, winding, or otherwise vascular grafts, patches, or other implantable medical devices. To be achieved. The material of construction is expanded PTFE
, Polyester, silicone, polyurethane, or any other biomedical material. The design of the device and the choice of radioisotope determines the duration and intensity of radioactivity. The biomedical material encloses and encapsulates the radioactive source from accidental leakage, providing a "spacer" between the radioactive source and the tissue to be treated.

Although the present invention contemplates five primary embodiments, those skilled in the art will appreciate the numerous possibilities based on the inventive concepts described herein. The first example involves incorporating a radioactive "seed" (coarse particles, granules, encapsulated radioactive fluid, or other radioactive particles) into the graft along its length or at the proximal and distal ends. The seeds can be placed in expanded PTFE or other biomedical material prior to extrusion (eg, coextrusion) or manufacture so that they are embedded in the graft and evenly distributed within the graft. The second example uses radioactive seeds embedded in biomedical material as in the first example, but the final product is wrapped around synthetic or natural blood vessels to prevent tissue growth. It is in the form of a "bandage". A third example incorporates a radioactive wire into a graft by coiling the wire along its length or at an isolated location (eg, near an anastomosis with a live vascular coil). In the case of a woven biomedical material (eg polyester), the wire may be woven at the same time as the biomedical material. The radioactive "wire" may actually be a bead of solid plastic (eg PTFE) containing radioactive powder or seeds. Such beads can be easily laminated to biomedical graft materials. The fourth example involves mixing radioactive material into the walls of the graft. Finally, the fifth embodiment uses an encapsulated stent graft with pockets filled with radioactive material. This embodiment can be used intraluminally or as an interventional graft.

Those skilled in the art will more fully understand the radioactive graft or cuff, and its additional advantages and objectives, by considering the following detailed description of the preferred embodiments. Please refer to the attached drawings.

[0013]

DETAILED DESCRIPTION OF THE INVENTION

The present invention fills the need for a medical device to eliminate restenosis, with incorporated radioactive elements. This is done by mixing the radioactive seeds or powder with PTFE or other biomedical material prior to extrusion of the device so that the radioactive elements are evenly distributed across the resulting graft or cuff. be able to. Another method of incorporation is to wrap the solid radioactive element (wire or bead) around the device during manufacture of the device or immediately prior to implanting the device in the body. It should be understood that various devices can be manufactured with non-radioactive components that are later rendered radioactive by neutron bombardment before use. This allows the device to be manufactured without the need to fear radioactive contamination of places or workers. In addition, neutron bombardment can be used to produce radioisotopes with a short half-life (ie, the radioactivity is significantly attenuated by the delivery time of the device) such that normal production and delivery are impractical.

Referring now to the accompanying drawings, wherein like reference numbers indicate similar or identical structures. FIG. 1 shows a first embodiment of a radioactive graft 10. This graft 10
It is made of a biomedical material (eg expanded PTFE) 14 with an embedded radioactive seed 12. These seeds 12 (solid particles or droplets of radioactive fluid) are either co-extruded with the material already in the radioactive state or are processed by neutron bombardment or the like after extrusion. The latter method of forming the radioactive seed 12 offers various advantages in terms of manufacturability, safety, and shelf life. If the material is PTFE or a similar substance, extrusion is described below with reference to FIG.

By embedding the radioactive seed 12 in the expanded PTFE cover 14, the use of radioactive material is widened. The flexibility of the radioactive graft 10 allows it to be used in many applications, such as inside or outside a stent. By using radioactive elements in the form of seeds, the radioactivity can be manipulated as needed. Thus, long-lived, low-energy isotopes can be used when relatively long-duration treatments are needed, while different isotopes can be used when relatively short and strong treatments are desired. it can.

FIG. 2 shows a second embodiment of the invention similar to the first embodiment. The radioactive cuff 20 includes a strip 24 made of any biomedical material, such as non-absorbable expanded PTFE, with an embedded radioactive seed 12. As shown in FIG. 2, the radioactive cuff 20 is bandaged around the tube 70 within the body so that the radioactive seed 12 irradiates the expanded cells 72 within the tube. The cuff 20 is extremely versatile and can be used in many different applications including treatment of malignant sites other than blood vessels, such as those found in bile duct synthetic exchangers. In fact, the radioactive cuff 20 can be used in almost any vessel or lumen in the body that is closed due to overgrowth. As with the first embodiment, the activity of the seed 12 can be selected based on the particular application of the device, but isotopes that have a very long half-life emitting relatively low energy radiation are usually preferred. As in all cases of the invention, expanded PTF
E avoids direct contact between the vascular tissue and the radiation source. The thickness of the expanded PTFE can be selected to provide the ideal spacing between the radiation source and the tissue.

FIG. 3 shows a third embodiment of the present invention. The graft structure 30 includes a graft or tubular member 3 extending along its length and having a radiant wire 32 wrapped around its outer surface.
Including 4. Beads made of PTFE or the like containing a radioactive substance may be used instead of the wires. The beads can be easily laminated to the graft in the same manner that wires of any suitable plastic material can be coated. If the biomedical material is a woven or knitted body, wires or beads can also be woven or braided into the structure. The graft structure 30 can be used in conjunction with a stent that uses the graft structure 30 to be inserted into a body lumen to cover either the inner surface or the outer surface of the stent. In this case, the radioactive wire 32 acts to reduce the likelihood of restenosis after stent deployment by eliminating proliferating cells. Possibly the radioactive wire or bead is confined to the end region of the graft 34 that is sutured to the patient's vasculature.
The radiant wire 32 can be adhesively attached to the graft. Alternatively, the wire may be coated with PTFE or other plastic (eg, by inserting the wire 32 into an elongated PTFE tube slightly larger than the wire 32). The coated wire can then be attached to the graft 34 by heat and pressure or using an adhesive.

FIG. 4 shows a fourth embodiment of the present invention. Also in this example, the radioactive substance is foamed PT.
Incorporated into FE or other biomedical material components. In this case, the radioactive material is in the form of a liquid and a radioactive solution is prepared, which solution encloses the small droplets in a small plastic shell. The resulting radioactive balls 42 are co-extruded with biomedical material to form a radioactive graft 40 with small pockets 46 filled with the radioactive balls 42. In addition to the co-extrusion technique, the graft 40 can also be formed by embedding or encapsulating the radioactive balls 42 after the graft is manufactured.

In the fifth example, as in the first and third examples, the radioactive substance or the radiopharmaceutical is directly contained in the wall of the expanded PTFE graft without forming the seed mass.
In this case, the radioactive material is provided in the form of a ground solid or powder which is coextruded with PTFE. Referring to the first, third, and fifth embodiments, FIG. 5 illustrates a ram extrusion assembly 50 for coextruding billets of material. The billet of material is in this case PTFE mixed with any of the radioactive materials described above.
Made of The ram extrusion assembly 50 includes an extrusion barrel 52, an extrusion die 54, a mandrel 56, and a ram 58. A billet of material 59 is placed in extrusion barrel 52. A force is applied to the ram 58 and pressure is applied to the billet of material 59. This pressure causes the billet of material 59 to be extruded around the mandrel 56 through an extrusion die 54, which exits as a tubular extrudate 60. The arrow 62 indicates the extrusion direction. The tube extrudate 60 is then expanded and sintered according to the expansion and sintering procedures performed on pure PTFE vascular grafts well known in the art. When using balls 42 in which the radioactive liquid is encapsulated in plastic, the encapsulation material is selected so that the extrusion process does not break the balls 42 and leave the radioactive liquid.

Having described the preferred embodiment of the radioactive graft, it will be apparent to those skilled in the art how to obtain the particular advantages of the present invention. Furthermore, it will be appreciated that various changes and modifications can be made without departing from the scope and spirit of the invention. Although illustrated with some examples of using expanded PTFE as a biomedical material, the concept of the invention described above illustrates that polyester, organosilicon, polyurethane, or any other biomedical that can be extruded or woven. It is equally applicable to materials. Further, the language used herein to describe the present invention, and its various examples, includes not only their generally defined meanings, but also their particular definitions herein. It should be understood. Thus, where the description herein is to be understood as having the meaning of one or more of the elements, its use in the claims should refer to the meaning set forth herein and to the term itself. It must be understood as including all meanings. Accordingly, the wording and definition of elements in the claims are defined herein and not only the combination of elements as described, but also substantially the same function to achieve substantially the same result. Includes all equivalent structures, materials, or acts for performing in a substantially similar manner. The embodiments described above should be considered exemplary rather than limiting. The invention is described in more detail in the claims.

[Brief description of drawings]

FIG. 1 is a perspective view of a first embodiment of the invention in which radioactive seeds are dispersed throughout the graft.

2 is a cutaway view of a second embodiment of the present invention in which the radioactive seeds of FIG. 1 are dispersed throughout the cuff-like device.

FIG. 3 is a perspective view of a third embodiment of the present invention with a radiative coil (wire or billet) wrapped around the graft.

FIG. 4 is a perspective view of a fourth embodiment of the present invention in which pockets of radioactive fluid are dispersed throughout the graft.

FIG. 5 is a schematic cross-sectional view of a mandrel-diassemble used to extrude a graft containing radioactive material (particularly PTFE).

[Procedure for Amendment] Submission for translation of Article 34 Amendment of Patent Cooperation Treaty

[Submission date] September 20, 2001 (2001.9.20)

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be amended] Claims

[Correction method] Change

[Contents of correction]

[Claims]

─────────────────────────────────────────────────── ─── Continued Front Page (51) Int.Cl. ⁷ Identification Code FI Theme Coat (Reference) A61P 9/08 A61M 37/04 F Term (Reference) 4C082 AA05 AC09 AE05 AG04 4C084 AA01 AA12 BA44 CA62 NA04 NA10 ZA392 4C097 AA16 BB01 BB09 CC04 CC14 DD02 EE06 EE08 EE09 EE13 MM02 MM04 4C167 AA46 AA47 AA50 AA52 AA56 AA58 AA74 BB02 BB05 BB06 BB12 BB14 BB26 BB43 CC09 DD01 FF05 GG03 GG04 H17 GG05GG46

Claims (21)

[Claims] 1. An implantable radioactive device for inhibiting the growth of tissue, the implantable radioactive device comprising a lower structure made of a pliable material and a radioactive element incorporated into the lower structure. 2. The implantable radioactive device of claim 1, wherein the underlying structure is a replacement vascular graft of a body vessel. 3. The implantable radioactive device of claim 1, wherein the lower structure is a cuff for placement on a body canal. 4. The implantable radioactive device of claim 3, wherein the radiative element comprises a plurality of radioactive seeds. 5. The implantable radioactive device of claim 4, wherein the radioactive seed is mixed with the lower structure and coextruded with the lower structure. 6. The implantable radioactive device of claim 2, wherein the radiative element comprises a plurality of radioactive seeds. 7. The implantable radioactive device of claim 6, wherein the radioactive seed is mixed with the lower structure and coextruded with the lower structure. 8. The implantable radiative device of claim 1, wherein the radiative element comprises a flexible wire. 9. The implantable radioactive device of claim 8, wherein the wire is a coil around the exterior of the vascular graft. 10. The implantable radioactive device of claim 8, wherein the wire is a coil around the interior of the vascular graft. 11. The implantable radiative device of claim 1, wherein the radiative element comprises a bead. 12. The implantable radioactive device of claim 11, wherein the wire is a coil around the exterior of the vascular graft. 13. The implantable radioactive device of claim 11, which is a coil around the interior of the vascular graft. 14. An implantable radioactive device according to claim 1, wherein the radioactive element comprises particles made of an encapsulated radioactive liquid. 15. The implantable radioactive device of claim 1, wherein the radiative element comprises small solid particles. 16. The implantable radioactive device according to claim 1, wherein the lower structure is expanded polytetrafluoroethylene, polyester, silicone rubber,
An implantable radioactive device made of a material selected from the group consisting of polyurethane and fluoropolymers. 17. An implantable radioactive device for inhibiting tissue growth comprising: an extruded member made of expanded polytetrafluoroethylene, and a plurality of radioactive sources incorporated into the extruded member and co-extruded with the extruded member. Including, device. 18. An implantable radioactive device for inhibiting tissue growth, the device comprising a tubular extruded member of expanded polytetrafluoroethylene and a radioactive wire wrapped around the tubular member. 19. The implantable radiative device of claim 19, wherein the radiative wire is coated with an organic plastic material. 20. The implantable radioactive device according to claim 19, wherein the plastic material is polytetrafluoroethylene. 21. A method for making an implantable radioactive device for inhibiting tissue growth, the method comprising: selecting particles made of a material capable of being radioactive, a plurality of non-radioactive particles, a plurality of polytetrafluoroethylene. Forming a mixture of particles and a liquid, forming an extrudate by extruding the mixture, foaming the extrudate, and treating the extrudate to render the non-radioactive particles radioactive Including the method.