MXPA99009662A - A radioactive medical suture and method of making the same - Google Patents

Abstract

A radioactive suture for inhibiting an intimal hyperplastic response comprises a needle and a suture material having a radioactive beta-emitting element. This radioactive element is preferably chemically bonded to an organic substrate of the suture material. It is preferred that the radioactive suture material generates a beta radiation greater than 0.0002 uCi/cm. A first preferred method for producing the radioactive suture comprises the steps of placing the suture needle and the suture material in a sealed reaction chamber. Once the suture is in the reaction chamber, an ionized beta radiation emitting element, preferably ionized tritium, is introduced into the chamber. While in the chamber, an entropic exchange process begins wherein the beta radiation emitting element is exchanged for hydrogen molecules in the organic suture material. Once the desired level of tritium or other beta radiation emitting element is incorporated in the suture material, the reaction chamber is flushed. The suture is then rinsed, dried, removed from the reaction chamber, and packaged. In another aspect, a radioactive suture may be fabricated from an organic polypropylene material. A beta radiation emitting element, preferably tritium, is incorporated directly into a backbone of the organic polypropylene material. The now radioactive polypropylene material is extruded into a suture thread, which is attached to a suture needle and packaged for shipment and later use. Although not required by the present inventive method, the preferred embodiment of the organic polypropylene material comprises carbon 12.

Description

RADIOACTIVE MEDICAL SUTURE AND METHOD FOR ELABORATION FIELD OF THE INVENTION The present invention relates generally to medical sutures for joining ends of biological tissue and, more particularly, to an apparatus and method for making a radioactive medical suture having beta radiation emission capabilities to inhibit a hyperplastic intimal response.

BACKGROUND OF THE INVENTION The sutures have been used to join ends of biological tissue to hold it in place until the joined tissues have time to heal. In patients with arterial occlusive disease, vascular surgeons use sutures to anastomose autogenous veins, prosthetic grafts or arteries to other arteries in order to make shunts around or replace diseased artery segments. Virtuality in all the anastomotic sites between the arteries and the autogenous veins, or between prosthetic grafts, can produce a rapid cell growth condition called "intimal hyperplasia". REF .: 31836 Intimal hyperplasia (below "IH") is the usual response to damage to blood vessels. This rapid cell growth, in response to damage to the cell lining of the blood vessels (intima), begins to narrow (stenosis) of the opening (lumen) between the vessels and / or in the graft to the point where an occlusion may occur . More specifically, IH forms as a result of the proliferation of smooth muscle cells, migration and deposition of the extracellular matrix. The interaction of platelets, macrophages, growth factors and cytosines plays an important role in the process. There are systemic regimens to avoid hyperplastic intimal response in animal models, but none has been shown to be beneficial in humans. IH is the main cause of "restenosis" (narrowing) in the first year after the vascular bypass operation, and may cause the introduced venous catheters to become occluded as well. The patient must also undergo another operation to check or replace the occluded graft. If a major vein is occluded (eg jugular or subclavian) there may be massive edema of the upper extremity, the face and the neck portion, and if an artery is occluded, it may possibly lead to potential loss of the limb. The most commonly performed prostate graft operation is a venous arterial conduit for dialysis in patients with chronic renal failure. Patients with renal dialysis require repetitive angioacceso to this arterial-venous graft for dialysis, to release the system of toxins. The most commonly used dialysis graft is a synthetic graft made of Teflon or PTFE (expanded polytetrafluoroethylene). Unfortunately, these grafts fail rapidly and have a primary occlusion rate of 15% to 50% during the first year, with an average patency of only 15 months. This failure in most cases is due to the development of intimal hyperplasia in the venous anastomosis. In recent years, studies have been carried out in animal models whose vessels have undergone angioplasty. It has been found that vessels in response to balloon angioplasty damage are similar to those seen in suture anastomotic lesions. The studies that have ended at Emory Universi and Vanderbilt University suggest that "restenosis" (narrowing) results mainly from the migration and rapid proliferation of a smooth muscle cell after balloon angioplasty. It has been demonstrated by these groups that very low concentrations of beta-particle irradiation introduced at the damage site after angioplasty significantly inhibit the proliferation and / or migration of smooth muscle cells. In a series of tissue culture experiments, a titanium wire of 0.20 mm diameter is impregnated with low concentrations of 32 P, and these wires are placed in cultures of smooth muscle cells of both rat and human. The activity level of the wire varies from 0.002 to 0.06 μCi / cm of wire. Compared to the control without radiation, it is found in the crops where the activity is >; 0.0006 μCi / cm there is a different zone of complete inhibition of smooth muscle cells that varies from 5.5 to 10.6 mm from the radioactive wire. It is hypothesized that if a low level radioactive wire can induce such an effect in the tissue culture, then a stent placed in vivo can alter or inhibit the restenotic activity in vessels undergoing angioplasty. Vanderbilt University together with the Walter Reed Army Medical Center conducted a series of experiments on iliac and coronary porcine models using radioactive Strecker stent. The first results in iliac model restenosis result in a 37% reduction in the area of neointima in stents of 0.14 μCi of 32P versus controls one month after the procedure. Additional in vitro tests performed with radioactive Palmaz-Schatz in coronary models showed portions of a reduction of up to 50% in the area of the neointima and a cross-sectional area of stenosis one month after the implantation of the sten.

From these initial reports, many additional studies have been carried out which have demonstrated and sustained these initial findings. Therefore, there is a need in the art for a suture that has a low level of radioactive particle emissions for the reduction and possible elimination of smooth muscle cell proliferation and therefore a hyperplastic response of the neointima at sites of anastomotic vessels, so that longevity is provided to the duration of the graft.

BRIEF DESCRIPTION OF THE INVENTION Briefly described, the present invention comprises a radioactive medical suture and a method for making a radioactive medical suture. It is now known that the proliferation of smooth muscle cells can be inhibited by varying the degrees and types of radiation, particularly low level beta radiation. This knowledge is exploited by the novel radioactive medical suture and the method described herein. Generally, the present invention utilizes a conventional means for manufacturing beta radiation sources using, in the preferred embodiments, tritium as the source initiator.

A preferred embodiment of a radioactive medical suture for inhibiting a hyperplastic intimal response comprises a needle made in a standard or conventional manner, well known to those familiar in the art. The radioactive suture also comprises a suture material having a radioactive element emitting beta radiation. This radioactive element is preferably chemically bonded to an organic substrate of the suture material. Although any beta-emitting element with the present invention can be used, the tritium element is the preferred embodiment of the present invention. Generally, tritium is replaced by elemental hydrogen within a polypropylene backbone of a medical suture whereby a constant low level source of implantable radiation is provided which will inhibit a hyperplastic response of the neointima. It is preferred that the radioactive suture material generates a beta radiation greater than 0.0002 μCi / cm. A first preferred method for producing the radioactive suture comprises the steps of placing a suture needle and a suture material in a sealed radiation chamber. Once the suture is in the reaction chamber, an ionized beta radiation emitter element is introduced into the chamber. Again, this beta radiation emitting element is preferably tritium. The suture is preferably left in the reaction chamber for one to several weeks. While in the chamber, a tropical exchange process begins where the tritium or other beta-emitting element is exchanged for hydrogen molecules in the organic suture material. Once the desired level of tritium or other beta-emitting element is incorporated in the suture material, the reaction chamber is discharged by a normal means included in the art. Then, the suture is rinsed and dried while it is still preferably in the reaction chamber. The suture is removed from the reaction chamber and packaged as a suture that is normally packaged in the art. Such normal packing usually involves placing the suture in a sealed foil pouch. Another preferred embodiment of a method for manufacturing a radioactive suture initially comprises an organic polypropylene material, a beta radiation emitting element, preferably C12 (carbon 12), is incorporated directly into the main structure of the organic material. In this way, a radioactive polypropylene material is generated. The polypropylene material is then extruded into a suture thread. This suture thread is then preferably attached to a suture needle and packaged for shipment and subsequent use. Although not required by the method of the present invention, in this second preferred embodiment, the organic polypropylene material comprises carbon 12. Since the source is of low level radiation, the safety measures necessary for its handling are minimal in comparison with other radioactive elements, and since the vehicle is a suture, there is no need to inject or implant other radioactive substances in a site. Despite the beta-emitting characteristics of the suture, its characteristics of resistance to stress or other physical properties are not lost. The benefits of the beta-radiation emitting polymer do not affect normal endothelial cell function, but will inhibit the IH response and will therefore "" improve graft patency and prevent early graft failure. Other objects, features and advantages of the present invention will be apparent to those familiar with the art. A more complete understanding of the invention will be obtained through a review of the detailed description set forth below.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a conventional vascular medical suture made of basic monofilament or braided hydrocarbon elements. A typical suture may be made of polypropylene or any other hydrocarbon-based suture as in the case of the family of surgical sutures with the trade name Prolene manufactured by Johnson and Johnson. Other sutures manufactured by different manufacturers such as Davis and Geck, US Surgical and other manufacturers can also be used as the carrier of the main structure for radioactive tritium. In the first preferred embodiment of the invention, a non-radioactive suture material is encapsulated within the sealed reaction chamber together with a needle, the suture then undergoes incorporation of tritium by means of the ilzbach method. This is a simple process for random labeling of organic molecules with tritium. In this process, ionizing tritium is introduced into the sealed reaction chamber to a level of about 15 Ci. By means of the process of entropic exchange of tritium by hydrogen, tritium is replaced within the organic matrix of the suture. The suture in the sealed reaction chamber is maintained in the ionizing field of tritium for a period of one day to several weeks, based on the amount of tritium to be incorporated and the level of activity of the required suture. Upon completion of the reaction, the reaction chamber is discharged in the usual manner understood by those familiar with the art and the suture is rinsed, dried and removed. Due to the low amount of beta radiation, suture management only requires the use of latex gloves. The packaging of the suture in a common aluminum foil suture bag is sufficient to contain the radioactivity of the incorporated tritium. A second preferred embodiment of the invention comprises making a suture from a radioactive polypropylene material. In this embodiment, the radioactive polypropylene is synthesized from the elemental components. In this method, tritium or other beta-emitting element is directly incorporated directly into the main structure of the organic compound. The element of choice in this configuration would be C12 (carbon 12). Once the radioactive compound has been formulated, it is then extruded to the desired yarn thickness and attached to a needle in a conventional manner and packaged. The drawback with this process is that it generates a large amount of equipment exposed to radioactivity that must be cleaned and handled properly. It will be apparent to those familiar with the art that many variations and modifications may be made to the preferred embodiment as described above, without departing substantially from the principles of the present invention. Such variations and modifications are intended to be included herein and to be within the scope of the present invention, as set forth in the following claims. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers.

Claims (12)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. A radioactive suture for inhibiting a hyperplastic intimal response, the suture is characterized in that it comprises: (a) a needle, - and (b) a suture material having a beta-emitting element chemically bound to an organic substrate of the material of suture, in which the suture material generates a beta radiation greater than 0.0002 μCi / cm.

2. The radioactive suture according to claim 1, characterized in that the needle is fixed to the suture material before the incorporation of the beta radiation emitting medium.

3. The radioactive suture according to claim 1, characterized in that the needle is fixed to the suture material after incorporation of a beta radiation emitting medium.

4. The radioactive suture according to claim 1, characterized in that the suture material comprises an extruded radioactive polypropylene material.

5. The radioactive suture according to claim 1, characterized in that the beta radiation emitting element comprises tritium.

6. A method for producing a radioactive suture to inhibit a hyperplastic intimal response, the method is characterized in that it comprises the steps of: (a) providing a sealed reaction chamber; (b) placing a needle and suture material in the chamber; and (c) introducing an ionized beta radiation emitter element into the chamber to cause a tropic exchange process of the beta radiation emitting element for hydrogen in the suture material.

The method according to claim 6, characterized in that it further comprises the steps of: (d) discharging the reaction chambers, - (e) rinsing the suture while the suture is in the reaction chamber; (f) drying the suture; (g) removing the suture from the reaction chamber; and (h) packing the suture in a package.

8. The method according to claim 6, characterized in that the beta radiation emitting element comprises ionized tritium.

9. A method for manufacturing a radioactive suture having beta-emitting tritium radiation, the method is characterized in that it comprises a conventional Wilzbach process. A method for manufacturing a radioactive suture, characterized in that the method comprises the steps of: (a) providing an organic polypropylene material; (b) incorporating a beta radiation emitting element directly into a main structure of the organic material, whereby a radioactive polypropylene material is generated; (c) extruding the radioactive polypropylene material into a suture thread, and (d) attaching the suture thread to a suture needle. The method according to claim 10, characterized in that the beta radiation emitting element comprises tritium. SUMMARY OF THE INVENTION A radioactive suture is provided to inhibit a hyperplastic intimal response, comprising a needle and a suture material having a radioactive element emitting beta radiation. This radioactive element is preferably chemically bonded to an organic substrate of the suture material. It is preferred that the radioactive suture material generates a beta radiation greater than 0.0002 μCi / cm. A first method for producing the radioactive suture comprises the steps of placing the suture needle and the suture material in a sealed reaction chamber. Once the suture is in the reaction chamber, an ionized beta radiation emitter, preferably ionized tritium, is introduced into the chamber. While still in the chamber, the process of exchange in the tropics begins where the beta-emitting element is exchanged for hydrogen molecules in the organic suture material. Once the desired level of tritium or other beta-emitting element is incorporated into the suture material, the reaction chamber is discharged. The suture is then rinsed, dried, removed from the reaction chamber and packaged. In another aspect, a radioactive suture material can be fabricated from an organic polypropylene material. A beta-emitting element, preferably tritium, is incorporated directly into the main structure of the organic polypropylene material. The now radioactive polypropylene material is extruded into a suture thread, which is attached to a suture needle and packaged for shipment and subsequent use. Although not required by the present method of the invention, the preferred embodiment of the organic polypropylene material comprises carbon 12.