Abstract:
This invention involves radioactive medical devices for inhibiting an undesirable hyperplastic response in biological tissue, and a method for making the radioactive medical devices. In a first preferred embodiment, a medical device for inhibiting a hyperplastic response in biological tissue generally comprises polymeric hydrocarbon molecules forming the medical device and a salt or an acid of a radioactive isotope occluded within the polymeric hydrocarbon molecules. In a second preferred embodiment, the medical device comprises a thrombogenic sponge having a radioisotope trapped within the structure of the sponge. Also in a preferred embodiment, a method of creating a medical device according to the present invention comprises: providing a first solvent in a container; introducing a salt or an acid of a radioactive isotope into the first solvent; introducing a second solvent into the first solution so as to form a second solution; and introducing the medical device into the second solution, wherein the ionic components of the radioactive isotope migrate into the molecular structure of the medical device. In another aspect, a method of creating a medical device that inhibits a hyperplastic response in biological tissue comprises placing a salt or an acid of a radioactive isotope in a fluid and permitting the salt or acid to disassociate in solution, submersing the sponge in the solution and permitting the radioactive isotopes to become trapped in the structure of the sponge.

Description:
CROSS-REFERENCE TO RELATED APPLICATION  
       [0001]    This application claims priority to copending U.S. patent application entitled, “Radioactive Medical Devices for Inhibiting a Hyperplastic Response and Method of Making Radioactive Medical Devices,” having Ser. No. 09/711,766, filed Nov. 13, 2000, which is entirely incorporated herein by reference. 
     
    
     
       TECHNICAL FIELD  
         [0002]    The present invention relates generally to medical devices and, more particularly, to a radioactive medical device having radiation emitting capabilities for inhibiting an undesired hyperplastic response to the healing of biological tissue, and a method for making and using the devices.  
         BACKGROUND OF THE INVENTION  
         [0003]    In patients with vascular disease, cardiovascular surgeons use sutures to anastomose autogenous vein, prosthetic grafts, or arteries to other arteries in order to bypass around or replace diseased vessel segments. At virtually all anastomotic sites between the arteries, veins, and autogenous vein, or prosthetic grafts, a condition of rapid cellular growth termed “intimal hyperplasia” may occur.  
           [0004]    Intimal hyperplasia is the usual response to blood vessel injury. This rapid cellular growth, as a response to injury of the blood vessel cellular lining, begins to narrow the opening between the vessels and/or graft to the point where an occlusion may occur. More specifically, intimal hyperplasia forms as a result of smooth muscle cell proliferation, migration, and extracellular matrix deposition. The interaction of platelets, macrophages, growth factors, and cytokines plays an important role in the process. Intimal hyperplasia is one of the primary cause of “restenosis” (narrowing) in the first year after vascular bypass operations. Usually, the patient must have another operation to revise or replace the occluded graft. If a major vein occludes (e.g. jugular or subclavian) massive edema of the upper extremity, face and neck may occur. If a limb artery occludes, it could possibly lead to potential limb loss.  
           [0005]    Of course, intimal hyperplasia is merely a subset of a larger problem involving hyperplasia resulting from smooth muscle cell proliferation, migration, and extracellular matrix deposition. In general, when biological tissue begins grafting, or healing, an undesirable hyperplastic response may occur. It would be desirable to limit, or even prevent such an unwanted hyperplastic response.  
           [0006]    One of the most frequently performed vascular surgical operation is an arterial to venous conduit for dialysis in chronic renal failure patients. Renal dialysis patients require repetitive angioaccess to this arterial-venous conduitive graft for dialysis to rid their system of the body&#39;s toxins. The most commonly used graft for dialysis in the United States is a prosethetic graft made from teflon or ePTFE (expanded polytetrafluroethylene). Unfortunately, as a consequence of repeated access by dialysis needles, these grafts fail frequently and have a primary occlusion rate of 15% to 50% during the first year, with a mean patency of only 15 months. One of the most common causes of failure in these grafts is due to the development of intimal hyperplasia at the venous anastomosis. Again, there is a strong desire in the art to prevent this unwanted hyperplastic response.  
           [0007]    Both examples of tissue grafting stated above, operations necessary to treat arterial occlusive disease and an arterial to venous conduit for dialysis, prescribe the use of a suture to assist the healing of biological tissue. However, there are several devices currently used in the medical field for assisting the grafting of biological tissue. Amongst which may be, “patches,” “wraps,” and meshes which give the tissues time to heal. Similarly, stents come in a variety of configurations for supporting blood vessel walls in an attempt to inhibit stenosis of the vessel.  
           [0008]    Surgical sutures are used to bring together ends of biological tissue and hold them in place until the joining tissues have time to heal. As another example, in some types of medical operations, medical personnel may use “patches” or meshes to support tissue in order to give the tissue appropriate time to heal. Just as with vascular bypass conduits, the tissue adjacent the “patch” or mesh may also exhibit signs of hyperplasia that are undesirable, if not harmful.  
           [0009]    In recent years, studies have been conducted in animal models whose vessels have undergone balloon angioplasty. It was found that the vessels response to injury from balloon angioplasty is similar to that observed at suture anastomotic sites. Studies conducted at Emory University, Atlanta, Ga., U.S.A., and Vanderbilt University, Nashville, Tenn., U.S.A., suggest that restenosis results primarily from the migration and rapid proliferation of a smooth muscle type cell after balloon angioplasty. It has been demonstrated by these groups that very low levels of beta-particle irradiation introduced to the site of injury following angioplasty markedly inhibits smooth muscle cell proliferation and or migration. Numerous other studies have been conducted which have demonstrated and substantiated these early findings.  
           [0010]    U.S. Pat. No. 5,897,573, filed Apr. 22, 1997, dealt with the problem of unwanted hyperplastic response in biological tissue by suggesting the irradiation of a suture material prior to its use in a patient. U.S. Pat. No. 5,897,573 describes how a low-level beta-emitting radioisotope may be incorporated into the chemical structure of suture material in order to inhibit an unwanted hyperplastic response. U.S. Pat. No. 5,897,573, filed Apr. 22, 1997, is hereby incorporated by reference as if fully set out herein.  
           [0011]    Similarly, U.S. Pat. No. 6,042,600, filed Jan. 25, 1999, dealt with the problem of unwanted hyperplastic response in biological tissue by suggesting the irradiation of various medical devices before use in a patient. U.S. Pat. No. 6,042,600 was a continuation in part of U.S. Pat. No. 5,897,573. U.S. Pat. No. 6,042,600 describes how a low-level beta-emitting radioisotope may be incorporated into the chemical structure of a medical device. U.S. Pat. No. 6,042,600, filed Jan. 25, 1999, is hereby incorporated by reference as if fully set out herein.  
           [0012]    Both of the two above-described patents generally prescribe chemically bonding the radioactive element to the structure of the medical device. However, there may be situations where it is not desirable to alter the chemical structure of the medical device to be used. Additionally, certain isotopes may not readily lend themselves to chemically attaching themselves to the molecules of the medical device. To remedy this need, U.S. Pat. Application having Ser. No. 09/711,766 was filed on Nov. 13, 2000. This patent application, also deals with radioactive medical devices. However, the devices are created by a process involving occluding salts of radioacitve isotopes into a molecular matrix of the medical device. U.S. Pat. Application having Ser. No. 09/711,766, filed Nov. 13, 2000, is hereby incorporated by reference as if fully set out herein.  
         SUMMARY OF THE INVENTION  
         [0013]    Generally described, the present invention provides a radioactive medical device having radiation emitting capabilities for inhibiting an undesired hyperplastic response to the healing of biological tissue, and a method for making and using the devices. It is known that smooth muscle cell proliferation may be inhibited by varying degrees and types of radiation, particularly low level beta radiation and low level gamma radiation. This knowledge is exploited by the radioactive medical devices and method described herein.  
           [0014]    In a first preferred embodiment, a method of creating a medical device that inhibits a hyperplastic response in biological tissue comprises the following steps: providing a first solvent in a container; introducing a salt or an acid of a radioactive isotope into the first solvent such that the salt or acid disassociates into ionic components so as to form a first solution; introducing a second solvent into the first solution so as to form a second solution; and introducing the medical device into the second solution, wherein the ionic components migrate from the second solution into the molecular structure of the medical device.  
           [0015]    In another aspect, a method of creating a medical device that inhibits a hyperplastic response in biological tissue comprises the following steps: providing an organic solvent in a container; introducing a salt or an acid of a radioactive isotope into the organic solvent such that the salt or acid disassociates into ionic components so as to form a solution; and introducing the medical device into the solution, wherein the ionic components migrate from the solution into the molecular structure of the medical device.  
           [0016]    In another aspect, a method of creating a medical device that inhibits a hyperplastic response in biological tissue comprises the following steps: providing an aqueous solution in a container; introducing a salt or an acid of a water soluble radioactive isotope into the aqueous solution such that the salt or acid disassociates into ionic components so as to form a second solution; and introducing the medical device into the second solution, wherein the ionic components migrate from the solution into the structure of the medical device.  
           [0017]    In a first preferred embodiment of a medical device for inhibiting a hyperplastic response in biological tissue, the medical device generally comprises polymeric hydrocarbon molecules forming the medical device and a salt or an acid of a radioactive isotope occluded within the polymeric hydrocarbon molecules. As a result of this structure, the radioactive isotope in the polymeric hydrocarbon molecules of the medical device inhibits a hyperplastic response in biological tissue.  
           [0018]    In another aspect of a medical device for inhibiting a hyperplastic response in biological tissue, the medical device comprises a thrombogenic sponge-like material having a radioactive isotope trapped within the structure of the sponge-like material. As a result of this structure, the radioactive isotope inhibits a hyperplastic response in biological tissue.  
           [0019]    Other systems, methods, features, and advantages of the present invention will be or will become apparent to one with skill in the art upon examination of the following drawings and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the present invention, and be protected by the accompanying claims. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0020]    The present invention can be better understood with reference to the following drawings. The drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present invention. Moreover, like reference numerals designate corresponding parts throughout the several views.  
         [0021]    [0021]FIG. 1 is a cut-away side view of the first step used in the method of the first preferred embodiment.  
         [0022]    [0022]FIG. 2 is a cut-away side view of the second step used in the method of the first preferred embodiment.  
         [0023]    [0023]FIG. 3 is a cut-away side view of the third step used in the method of the first preferred embodiment.  
         [0024]    [0024]FIG. 4 is a plan view of a mesh material of the first preferred embodiment.  
         [0025]    [0025]FIG. 5 is an exploded top depiction of the fibers of the mesh material depicted in FIG. 4.  
         [0026]    [0026]FIG. 6 is a cut-away side view of the first step used in the method of the second preferred embodiment.  
         [0027]    [0027]FIG. 7 is a cut-away side view of the second step used in the method of the second preferred embodiment.  
         [0028]    [0028]FIG. 8 is a cut-away side view of the first step used in the method of the third preferred embodiment.  
         [0029]    [0029]FIG. 9 is a cut-away side view of the second step used in the method of the third preferred embodiment. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0030]    The present invention relates to conventional implantable medical devices that are designed to emit localized, low-level beta radiation while in or near biological tissue. The present invention also relates to both a method of preventing hyperplasia in biological tissue grafts and a method of creating medical devices that accomplish this goal.  
         [0031]    Creation of the medical device of the present invention by a first preferred method begins with the selection of a radioactive isotope to be occluded into the molecular structure of the medical device. The preferred radioisotopes for the present invention are beta-emitting or gamma-emitting radioisotopes with relatively long half-lives. For purposes of this disclosure, a relatively long half-life is generally considered any half-life in excess of 150 days. However, it is possible to use radioisotopes with much shorter half-lives, as will be demonstrated below. Additionally, many of the radioisotopes that may be used have much longer half-lives than 150 days.  
         [0032]    The preferred radioisotopes also emit a relatively low level of radiation. For purposes of this disclosure, a low level of beta radiation is generally in the range of 1000 uCi. Also for purposes of this disclosure, a low level of gamma radiation is similar to that of the beta range. Of course, one with skill in the art can readily determine the appropriate level of radiation to inhibit an undesired hyperplastic response. Such a level of radiation may not necessarily be within the above-specified range, and the present invention is not meant to exclude beta or gamma radiation values outside of this range. The range of radiation values is only illustrative and preferred for the particular embodiment described herein.  
         [0033]    The following are examples of preferred beta-emitting radioisotopes: Calcium 45; Chlorine 36; Prometheum 147; Strontium 90; and Technitium 99. The following are examples of preferred gamma-emitting, and sometimes also beta-emitting, radioisotopes: Cobalt 60; Yttrium 90; Scandium 46; Cerium 141; Sodium 22; and Manganese 54. Most of the radioisotopes listed as examples have relatively long half-lives. Exceptions to this general property can be found with Scandium 46 (83 day half life) and Cerium 141 (32 day half life). This illustrates that radioisotopes with half lives of less than 150 days may also be preferred, depending on the particular application.  
         [0034]    Although radioisotopes with short half-lives may also be effective with the present invention, a long half-life is preferred mainly due to storage and shipping concerns. Over time, the quantity of radioactivity of a radioisotope will decrease due to nuclear decay. The half-life is a measure of the rate of this decrease in radioactivity. If the quantity of radioactivity of the radioisotope decreases too rapidly, the medical device must be used almost immediately after manufacturing. This leaves no time for shipping and no flexibility as to storage of the medical device. For example, Prometheum 147, one of the above-listed radioisotopes, has a half-life of approximately 2.5 years. If Prometheum 147 is selected for the present invention, the 2.5 year half-life would provide ample time for manufacture, shipment, and storage. Then, when the medical device is needed, it still exhibits radioactive properties in adequate levels to provide the needed effect.  
         [0035]    In the first preferred embodiment 10 of the present invention, Calcium 45 is selected. Calcium 45 is preferred for a variety of reasons. To begin, Calcium 45 has a half-life of about 163 days. This length of half-life is long enough to allow shipment and storage of the medical device. However, the fact that the half-life is not several years means that the medical device will not continue to be radioactive for many years after what is required to inhibit an undesirable hyperplastic response in a patient&#39;s biological tissue.  
         [0036]    In the first preferred embodiment 10 of the method described below, the radioactive isotope, Calcium 45, is not used alone. Rather, a salt or an acid of the radioisotope is preferred. So, for example, the preferred isotope of Calcium 45 is used in the form of its salt, radioactive Calcium Chloride ( 45 CaCl 2 ). Of course, Calcium 45 could also be used in its acid form, however, in the preferred embodiment described below, radioactive Calcium Chloride is preferred. Even if the salt form of Calcium 45 is used, other salts are possible. For example, radioactive Calcium Fluoride ( 45 CaF 2 ) is a possible radioactive salt that can be used with the first preferred embodiment 10.  
         [0037]    The other radioisotopes listed above can also be used in their salt or acidic form. For example, Chlorine 36 is used in the form of either radioactive Calcium Chloride (Ca 36 Cl 2 )or radioactive Hydrochloric Acid (H 36 Cl); Prometheum 147 is used in the form of radioactive Prometheum Chloride ( 147 PmCl 3 ); Strontium 90 is used in the form of radioactive Strontium Chloride ( 90  SrCl 2 ) or radioactive Strontium Nitrate ( 90 SrNo 3 ); and Technitium 99 is used in the form of radioactive Technitium Fluoride ( 99 TcFl 5 ). As for the gamma-emitters listed above, for example, Cobalt 60 is used in the form of radioactive Cobalt Chloride ( 60 PmCl 2 ); Scandium 46 is used in the form of radioactive Scandium Chloride ( 46 ScCl 3 ); Cerium 141 is used in the form of radioactive Cerium Chloride ( 141 CeCl 3 ); Sodium 22 is used in the form of radioactive Sodium Chloride ( 22 NaCl); and Manganese 54 is used in the form of radioactive Manganese Chloride ( 54 MnCl 2 ).  
         [0038]    The gamma-emitting radioisotope Yttrium 90 deserves special mention. If Strontium 90 is used in one of the forms listed above, as the Strontium breaks down, Yttrium 90 is the natural result. Thus, if Strontium 90 is selected, then the medical device will emit beta radiation for a time, and then will emit a low-level gamma radiation for the half-life of Yttrium 90. The radioactive Sodium Chloride mentioned above also has this characteristic. That is, radioactive Sodium Chloride initially emits beta radiation, and then over time, begins emitting gamma radiation as the Sodium 22 breaks down.  
         [0039]    FIGS.  1 - 3  depict a first preferred embodiment 10 of a method for creating a radioactive medical device according to the present invention. In FIG. 1, a container  11  is depicted with a solvent  12  in the container  11 . The container has a body portion  13  and a neck portion  14 . Initially, the solvent  12  is placed in the body  13  of the container  11 .  
         [0040]    The solvent  12  of the first preferred embodiment  10  is a protic solvent. More specifically, the preferred protic solvent for the present invention is Ethyl Alcohol (C 2 H 5 OH). Of course, other protic solvents may be used, such as ethyl acetate (CH 3 COOC 2 H 5 ) or toluene (C 6 H 5 CH 3 ). In the specific preferred embodiment described herein, the amount of Ethyl Alcohol is 0.5 milliliters. The amount of solvent  12  will generally vary with the size of the medical device to be immersed in the radioactive solution and other practical considerations. One skilled in the art will be able to determine the appropriate amount of solvent  12  to be used for a specific application.  
         [0041]    Although glass is the preferred material of the container  11 , other types of containers may be used. Generally, it is desirable to use a container  11  that is relatively non-reactive. Also, the shape of container  11  depicted in FIG. 1 is also not important to the present invention. Any shape will suffice, as long as the opening of the container  11 , as defined by the neck  14 , is sufficiently large to accept a medical device to be exposed to a radioactive solution in the container  11 . As will be outlined below, the container  11  of the preferred embodiment is also able to accept a lid, or to be sealed in some other way.  
         [0042]    The preferred form of a radioisotope  16  is added to the Ethyl Alcohol 12. See FIG. 1. As noted above, the preferred radioisotope is a salt of the beta-emitting Calcium 45, radioactive Calcium Chloride ( 45 CaCl 2 ). Other salts or acids could be used. Also, a gamma-emitting radioisotope could also be used. In the preferred embodiment, 60 millicuries of radioactive Calcium Chloride 16 is added into the container  11  and allowed to dissolve in the Ethyl Alcohol 12. In this way, the Ethyl Alcohol 12 serves to reduce the radioactive Calcium Chloride 16 into solution. When introduced into the Ethyl Alcohol 12, the radioactive Calcium Chloride 16 dissociates into its component ions:  45 Ca (+)  and Cl (−) . The radioactive Calcium Chloride 16 will remain dissociated into solution without any solid crystals in the container  11 . Physically, the Ethyl Alcohol 12 forms a type of matrix around the  45 Ca (+)  and Cl (−)  ions in order to keep the ions dissociated in solution form.  
         [0043]    The solution  17  formed by the radioactive Calcium Chloride 16 and the Ethyl Alcohol 12 is depicted in the container  11  in FIG. 2. Once the radioactive Calcium Chloride 16 is dissolved into the Ethyl Alcohol 12, a second solvent  18  is added to the container  11 , as depicted in FIG. 2. This second solvent  18  is preferably capable of expanding the molecular matrix of a polymer structure. To this end, the preferred second solvent  18  is Methylene Chloride (CH 2 Cl 2 ). However, dimethylformamide and tetrahydrofuran would also function adequately, although they typically do not function as well as Methylene Chloride.  
         [0044]    In the first preferred embodiment 10, 19 milliliters of Methylene Chloride 18 is added to the container  11  in batches of less than 5 milliliters at a time. In the first preferred embodiment 10, a glass pipette  19  is used to hold and then dispense the 19 milliliters in four separate batches. In this way, the Methylene Chloride 18 is slowly added to the solution  17  in the container  11 . The Methylene Chloride 18 is added slowly to the solution  17  in order to prevent causing the  45 Ca (+)  and Cl (−)  ions to leave solution and form crystals of radioactive Calcium Chloride along the bottom of the container  11 .  
         [0045]    The combination of Methylene Chloride 18 and the Ethyl Alcohol/Calcium Chloride solution  17  form a new solution  21 . Because Methylene Chloride 18 and Ethyl Alcohol 12 are miscible fluids, the new solution  21  will be a blend of Methylene Chloride 18 and Ethyl Alcohol 12. Because the  45 Ca (+)  and Cl (−)  ions are in ionic suspension within the Ethyl Alcohol 12, the new solution  21  will generally comprise an homogenous distribution of  45 Ca (+)  and Cl (−)  ions.  
         [0046]    Once all the Methylene Chloride 18 has been added to the container  11 , a medical device  22  to be exposed to the radioactive solution  21  is placed in the container  11 . In the first preferred embodiment 10, the medical device  22  is a mesh material, as shown more clearly in FIG. 4. The mesh material  22  is preferably constructed of polypropylene. In use, a medical practitioner may wrap this polypropylene mesh  22 , once it is labeled with a beta emitting radioactive substance, around a graft site in order to bathe the site with beta radiation. The use of this particular medical device  22  will be described in greater detail below.  
         [0047]    Of course, many different types of medical devices may benefit from having the capacity to emit low level localized beta or gamma radiation, and the present invention is not intended to be limited to a polypropylene mesh. Generally, any place that a medical device may be used in a body, the advantages afforded by the capability of emitting beta or gamma radiation may be helpful. For example, and without limitation, the medical devices of the present invention may comprise: surgical sutures, stents, surgical patches, anti-thrombogenic coatings, hydrophilic coatings, coverings or weavings over stents, fabric or mesh implants in the body, coatings on or woven into plastic catheters (e.g. dialysis catheters), biodegradable materials, thrombogenic sponges and gelfoams, and ocular lens implants.  
         [0048]    As noted above, in the first preferred embodiment 10, the mesh  22  is constructed of a polypropylene material. Polypropylene is a biocompatable material. However, in an alternative embodiment, the mesh material could be another biocompatable hydrocarbon material, such as polyethylene. In another alternative embodiment, the mesh material could comprise a biodegradable material.  
         [0049]    As depicted in FIG. 3, the mesh  22  is placed in the solution  21 . The mesh  22  is preferably completely submerged within the solution  21 . Once the mesh  22  is placed in the container  11 , a covering  23 , or lid, is placed on the neck  14  of the container  11  in order to seal the container  11 . If no lid  23  is used, the solution  21  will likely begin to evaporate. This may be undesirable if the mesh  22  is to stay in the solution  21  for several days.  
         [0050]    Once the mesh  22  is in the solution  21 , the Methylene Chloride  18  in the solution  21  expands the polypropylene matrix  24  and the  45 Ca (+)  and Cl (−)  ions begin migrating into and among the molecular structure  24  of the polypropylene mesh  22 . The mesh  22  is left in solution  21  until the desired concentration of radioactive Calcium is reached. In other words, the mesh  22  is left in solution  21  until it has incorporated the desired level of radiation-emitting characteristics. The migration of the radioactive Calcium may take anywhere from a day, to several days, to several weeks. The length of time necessary for migration of the radioactive ions into the molecular structure of the mesh  22  depends on the concentration of the radioactive ion present in the solution. In the preferred example, a one inch square of polypropylene mesh  22  is preferably left in the container  11  for 6-8 weeks.  
         [0051]    One skilled in the art can readily determine the appropriate length of time to expose the mesh  22  to the radioactive Calcium in the solution  21 . For example, small portions of the mesh  22  can be cut and tested to determine the level of radiation emitted by the irradiated mesh  22 . If the level is too low, then the mesh  22  is left in solution  21 . On the other hand, if the level of radioactive Calcium in the mesh  22  has reached equilibrium, or the desired level of radioactivity, then the mesh  22  is removed from the solution  21 .  
         [0052]    After reaching the desired concentration of radioactive material in the mesh  22 , the mesh  22  is removed from the container and permitted to dry. As the mesh  22  dries, the  45 Ca (+)  and Cl (−)  ions re-form radioactive Calcium Chloride ( 45 CaCl 2 ) crystals  16 , while still in the plastic mesh  22 . It should be recalled that the Methylene Chloride caused the plastic fibers  24  to swell when the mesh  22  was placed in the solution  21 . At the same time the  45 Ca (+)  and Cl (−)  ions are reforming radioactive Calcium Chloride 16, the drying process causes the polypropylene matrix  24  of the mesh  22  to shrink back to its original shape. This shrinkage causes the radioactive Calcium Chloride crystals  16  to become occluded in the polypropylene molecules  24 . FIG. 5 depicts an exploded view of one strand of the mesh  22  in order to demonstrate the occlusion of the radioactive Calcium Chloride 16 in the polypropylene fibers  24  of the mesh  22 . Thus, radioactive Calcium Chloride crystals  16  are dispersed throughout the plastic polymer structure and held in place by the polypropylene matrix  24 .  
         [0053]    In the first preferred method  10 , after drying is complete, the mesh  22  is rinsed several times with Ethyl Alcohol 16. Rinsing the mesh  22  removes any remaining Methylene Chloride 18 from the fibers and also removes any radioactive Calcium Chloride molecules that are not trapped within the molecular structure  24  of the mesh  22 . Rinsing the mesh  22  with Ethyl Alcohol 16 also serves to clean and sterilize the mesh material.  
         [0054]    Ethyl Alcohol is not the only liquid that may be used to rinse the mesh material. If rinsing is desired, the mesh may be rinsed with a variety of other solutions which are equally effective at removing Methylene Chloride and free radioactive ions. Of course, rinsing the mesh material is not required by the present invention.  
         [0055]    Generally, a solvent like Methylene Chloride will re-expand the polypropylene fibers  24  of the mesh  22 , thereby releasing the radioactive Calcium Chloride crystals  16 . Water and bodily fluids are typically not of this nature and will not re-expand the molecular chain structure  24  of the polypropylene mesh  22  sufficiently to release the radioactive Calcium Chloride crystals  16 . So, the radioactive calcium chloride molecules  16  stay trapped in the molecular structure  24  of the mesh  22  and will not migrate out of the mesh  22  when the mesh  22  is either handled or implanted into a patient&#39;s body.  
         [0056]    The mesh  22  of the first preferred embodiment 10 is typically used in surgical procedures in order to inhibit hyperplasia resulting from smooth muscle cell proliferation, migration, and extracellular matrix deposition. As noted above, when biological tissue begins healing, an undesirable hyperplastic response may occur, such as intimal hyperplasia. The mesh material  22  of the preferred embodiment may be used to inhibit this undesirable hyperplastic response.  
         [0057]    In order to use the mesh  22  to inhibit an unwanted hyperplastic response, a surgeon typically wraps the mesh  22  of the preferred embodiment around a site where tissues have been grafted, such as by a suture. Once the mesh  22  is placed around the graft site, the surgeon simply stitches the ends  26 ,  27  of the mesh  22  together in order to secure it in place. Of course, anywhere biological tissues are grafted together, the mesh  22  of the preferred embodiment will be very beneficial in preventing undesirable hyperplasia. For example, the mesh  22  could be placed between the tissues to be grafted. In this way, the device holding the tissue together, such as a suture, would also secure the mesh  22  into place. One with skill in the art will be able to see many additional uses for the medical device  22  of the first preferred embodiment 10.  
         [0058]    The method of incorporating radioactive material into a medical device described with regard to a polypropylene mesh  22  above could be used similarly to radioactively label a whole host of medical devices. Such devices may include (without limitation): surgical sutures, stents, surgical patches, anti-thrombogenic coatings, hydrophilic coatings, a covering or weaving over stents, fabric or mesh implants in the body, coatings on or woven into plastic catheters (e.g. dialysis catheters), biodegradable materials, thrombogenic sponges or gelfoams, and ocular lens implants. If one of these other medical devices are radioactively labeled by the above-described method, then these devices will also inhibit undesirable hyperplasia.  
         [0059]    If certain medical devices are used with the present invention, such as suture material for example, then it may be desirable to incorporate the preferred salt of a radioactive isotope into a polymeric hydrocarbon material before the medical device is actually made, or while the device is being made. For example, Calcium 45, or other beta or gamma emitting isotope could be introduced into the polymeric hydrocarbon material during a blending or extruding process used to make the medical device.  
         [0060]    Also, certain medical devices may permit the use of alternative methods of making the medical device radioactive. For example, it is common in various types of surgical procedures to use a sponge-like material to assist in achieving hemostasis at a graft site. Such sponges are typically constructed of a synthetic cellulose material, although the present invention is not limited to sponges constructed from this particular material. One such hemostatic agent is a thrombogenic sponge product known as Gelfoam®, manufactured by the Pharmacia Corporation.  
         [0061]    These thrombogenic sponge-like materials, like Gelfoam®, typically are manufactured into substantially planar sheets resembling a Styrofoam-like material. The sponge material may be treated with prothrombin, although not required by the present invention. Prothrombin is basically a carbohydrate-protein compound that is naturally occurring in blood plasma. Prothromin is essential to blood clotting. For use, medical practitioners cut the material to the size of sponge needed. When ready for use, the medical practitioner places the “patch” of sponge material in an aqueous solution, usually isotonic saline. Sponge-like materials, such as Gelfoam®, are typically water soluble, though not immediately soluble. Therefore, the sponge begins to soften in the aqueous solution, although this takes some time.  
         [0062]    If the sponge is treated with prothrombin, the aqueous solution also serves to convert the prothrombin into thrombin. When used in the body, this thrombin will convert fibrinogen into fibrin at the graft site, which along with the patient&#39;s platelet cells, will assist in clotting.  
         [0063]    Once the sponge-like material becomes pliable, the medical practitioner may better use the sponge. The medical professional removes the sponge from the solution and places it on the site to be treated. Materials of this type are used at suture-line sites to assist in the establishment of hemostasis. One of the advantages of using the sponge is that the sponge circumferentially covers the site so that the site is fully bathed with the thrombin, or other material delivered to the site by the sponge.  
         [0064]    It would be beneficial in many application if the sponge material were treated so that it emitted radiation in order to inhibit a hyperplastic response. Thus, the sponge could be used to both assist in the clotting function and then inhibit hyperplasia. Because sponges like Gelfoam® are typically not constructed of hydrocarbon molecules, the first preferred embodiment for incorporating a radioisotope into a medical device described above may not be entirely successful in incorporating radioisotopes into the structure of the sponge. The Methylene Chloride of the above-described method will not cause the molecular structure of the sponge to swell appreciably in the same manner as it causes plastic molecules to swell. Also, because the sponge is water soluble, the protic solvent of the first preferred embodiment will begin to dissolve the sponge. This is not desirable until immediately before the sponge is to be used by the medical practitioner.  
         [0065]    For these reasons, in a second preferred embodiment of a method for making a radioactive medial device a surgical sponge material, such as Gelfoam®, is caused to incorporate a radioisotope for delivery to an injury site in a patient. FIGS.  6 - 7  depict the second preferred embodiment 30 of a method for creating a radioactive medical device according to the present invention. In FIG. 6, a container  31  is depicted. The container has a body portion  33  and a neck portion  34 . Although glass is the preferred material of the container  31 , other types of containers may be used. Generally, it is desirable to use a container  31  that is relatively non-reactive. Also, the shape of container  31  depicted in FIG. 6 is not important to the present invention. Any shape will suffice, as long as the opening of the container  31 , as defined by the neck  34 , is sufficiently large to accept the sponge material to be exposed to a radioactive solution in the container  31 . The container  31  of the preferred embodiment is also able to accept a lid, or to be sealed in some other way. However, an alternative container would comprise a simply glass dish.  
         [0066]    As depicted in FIG. 6, an organic solvent  32  is placed in the container  31 . The preferred organic solvent  32  is ethanol. However, many other organic solvents would function with the preferred embodiment, as would be understood by one having ordinary skill in the art. Once the organic solvent  32  is in the container  31 , a radioactive nonwater soluble salt  36  is added to the organic solvent  32 . The radioactive non-water soluble salt  36  of the second preferred embodiment 30 is radioactive Calcium Carbonate ( 45 CaCO 3 ). The preferred radioactive Calcium Carbonate uses Calcium 45, which has all the advantages outlined above with respect to the first preferred embodiment 10. Of course, other non-water soluble salts could also be used with the second preferred embodiment 30 if a different radioisotope is preferred. For example, if Strontium 90 is the preferred radioisotope,  90 Sr(PO 4 ) 2  is an appropriate non-water soluble salt of Strontium 90.  
         [0067]    The radioactive Calcium Carbonate 36 will disassociate in the organic solvent  32  into  45 Ca (++)  and CO 3   (−−)  ions. The organic solvent  32  and the ionic components of radioactive Calcium Carbonate will form a solution  37  in the container. The Calcium Carbonate typically fully dissolves in about 24 hours. One with ordinary skill in the art will readily be able to determine the time needed to permit radioactive Calcium Carbonate 36 to dissociate in the organic solvent  32 .  
         [0068]    Once the radioactive Calcium Carbonate 36 dissociates into solution  37 , a sponge  42  to be treated is placed in the solution, as shown in FIG. 7. Because the sponge  42  in the preferred embodiment 30 is water soluble, the sponge  42  will not begin to break down in the organic solvent solution  37 . However, the  45 Ca (++)  and CO 3   (−−)  ions will begin to migrate into the structure of the sponge  42 . It is preferred that that sponge material absorb adequate  45 Ca (++)  ions to give the sponge a level of radioactivity need to inhibit a hyperplastic response in biological tissue. This level of radioactivity could be, for example, about 250 uCi per square inch of sponge  42 . To achieve this level of radioactivity, the solution  37  is preferably proportioned with radioactive Calcium Carbonate and organic solvent so that it exhibits radioactivity of about 10 mCi/ml. Once the sponge  42  is submerged in the solution  37 , a lid  43  is added to cover the neck region  34  of the container  31 . The sponge material  42  is preferably left in the solution  37  up to about 7 days, although the present invention is not so-limited. The time the sponge  42  is left in the solution  37  depends on the properties, size and thickness of the sponge  42 .  
         [0069]    Once the desired level of radioactivity is reached, the sponge material  42  is removed from the solution  37  and allowed to dry. As the sponge  42  dries, the  45 Ca ++  and CO 3   −−  ions will reassociate into radioactive Calcium Carbonate. However, the radioactive Calcium Carbonate will be trapped within the natural fibers and recesses of the sponge material  42 . Once dry, the sponge  42  may then be packaged and shipped to a medical professional for use.  
         [0070]    As noted above, when ready to use the sponge material, the medical professional typically places the sponge in an aqueous solution. As radioactive Calcium Carbonate is not water soluble, the ions will not dissociate in the aqueous solution. Thus, when the sponge is removed from the aqueous solution and placed in or on biological tissue, the radioactivity of the sponge is preserved. That is, radioactivity is typically not left in the aqueous solution.  
         [0071]    In certain applications, it may be desirable to treat a portion of the sponge material with a radioisotope shortly before using the sponge. This can be accomplished by a method of radiating a medical device according to a third preferred embodiment 50. FIGS.  8 - 9  show the basic steps of a method according to the third preferred embodiment 50. In the third preferred embodiment 50, a portion of sponge material  51  may be provided to the medical professional as part of an activation kit. This kit contains a patch-like portion of sponge  51 , a pre-measured quantity of a water soluble radioactive salt or acid, and a pre-measured quantity of an aqueous solution. The portions of the kit are measured so as to yield the desired level of radioactivity to the sponge. With knowledge of the third preferred embodiment 50 described below, one with ordinary skill in the art can determine the appropriate amounts of salt and aqueous solution.  
         [0072]    In the preferred kit, 1 ml of radioactive Calcium Chloride ( 45 CaCl 2 ) at 10 mCi/ml, the preferred radioactive salt, is packaged in a glass vial. Furthermore, 100 ml of isotonic saline solution, the preferred aqueous solution, is also packaged in a small glass vial. The sponge  51  can vary in size depending on the application.  
         [0073]    When ready to use the sponge  51 , the medical professional simply mixes the radioactive Calcium Chloride 52 and the isotonic saline  53  in a container  54 , such as a glass dish. As discussed above, radioactive Calcium Chloride 52 is water soluble and, therefore, dissociates into  45 Ca (+)  and Cl (−)  ions in the isotonic saline  53 , forming a solution  56 . Then, the sponge  51  is placed in the container  54  and bathed with the solution  56 . See FIG. 9.  
         [0074]    As the water-soluble sponge  51  begins to break down in the solution  56 , the  45 Ca  (+)  and Cl (−)  ions become trapped within the fibers and natural recesses of the sponge  51 . Therefore, when the sponge  51  is removed from the container  54  by the medical professional for use in a patient, a portion of the  45 Ca  (+)  ions are carried by the sponge  51  to the treatment site.  
         [0075]    In the third preferred embodiment 50, the radioactive isotope Calcium 45 was selected as the preferred radioactive isotope. However, at least any of the other radioisotopes listed above could also easily be used with the third preferred embodiment 50. Additionally, Calcium 45 was selected to be used in the salt form of radioactive Calcium Chloride. However, Calcium 45 could also be used in non-water soluble salts, such as radioactive Calcium Fluoride ( 45 CaF 2 ), for example. Additionally, the Calcium 45 could also be used in its acid form.  
         [0076]    With all the preferred embodiments and elements described above, it would be apparent to one skilled in the art that many variations and modifications may be made to the preferred embodiments (i.e. preferred nonlimiting examples) as described above without substantially departing from the principles of the present invention. Such variations and modifications are intended to be included herein and are within the scope of the present invention, as set forth in the following claims.