GB2352635A

GB2352635A - Medical stents

Info

Publication number: GB2352635A
Application number: GB9917894A
Authority: GB
Inventors: Martin Terry Rothman; Timothy David Warner
Original assignee: Individual
Current assignee: Individual
Priority date: 1999-07-31
Filing date: 1999-07-31
Publication date: 2001-02-07
Anticipated expiration: 2019-07-31
Also published as: GB9917894D0; GB2352635B

Abstract

A stent which has been subjected to a first treatment so that after it has been located at the target area within a patient and subjected to a further treatment causes the stent to become radioactive. To reduce incidence of restenosis. According to a first aspect of the invention, the stent is coated with an antigen or antibody and a radioactive antibody or antigen respectively is introduced into the bloodstream to bind to the stent coating and thus make it radioactive. According to a second aspect, the stent is rendered magnetic and a radioactive and magnetic substance is introduced into the bloodstream to bind to the stent.

Description

2352635 MEDICAL STENTS The present invention relates to medical stents

which are designed to be inserted, for example, into a patient's artery in order to maintain the cross-sectional area of the artery's lumen and, thus, ensure a satisfactory rate of blood flow through the artery.

Coronary arteries are composed mostly of smooth muscle cells lined by endothelial cells, which separate the smooth muscle from the blood. Narrowing of coronary arteries due to deposition of cholesterol in their walls (atherosclerosis) is the major cause of heart attacks and angina. It is often treated by angioplasty. In this procedure usually a special catheter is passed into the lumen of the diseased artery via an artery in the leg, and the tip of the catheter is then inflated at the site of the lesion, so as to stretch the wall there and allow more blood to flow through. A small device, usually made of metal, called a stent, is then put in place, so as to keep the lumen open. The endothelial cells may be damaged during this process, thereby exposing the underlying tissue to the blood. The remaining endothelial cells multiply and grow over the stent and the exposed muscle cells.

In many patients the lurnen of the artery narrows again at the site of insertion of the treatment. This is known as restenosis. It is not due to deposition of cholesterol, as was the original lesion, but to a combination of several factors, in response to the damage to the endothelial cells, the exposure of the underlying smooth muscle cells and other tissues to the blood, and contact between the blood and the stent. The factors that may lead to restenosis may include:

(1) Adherence of platelets (small blood cells) to the stent and smooth muscle. (2) Adherence of white blood cells to damaged endothelial cells, followed by their migration into the artery wall. (3) Formation of a blood clot on the surface. And (4) Overgrowth of smooth muscle cells in the artery wall around.

It is very likely that restenosis could be prevented if a way could be devised of stimulating the growth of endothelial cells over the stent, simultaneously preventing the deposition of platelets and white blood cells, blood clotting and overgrowth of smooth muscle cells while this is taking place. To date drugs have had very disappointing results. This can probably be attributed to two factors: (1) They inhibit only one or other of the different processes involved; and (2) They are not concentrated at the site of the treatment, but distributed throughout the body. As a result restenosis remains a major clinical problem.

Medical stents are well-known devices which have been available for many years and they can take a wide variety of constructional forms.

The present invention is particularly concerned with providing radiation therapy to coronary artery lesions and minimising restenosis.

The basic concept behind the present invention is the use of an appropriately treated stent to provide localised or targeted medical treatment to an area of a patient's body. The area could be, for example only, a cardiac artery, a part of the bilary tree, airways or the oesophagus. The treatments could be various and multiple and in the latter case delivered at different times by the same stent.

According to a first aspect of the present invention a stent is subjected to a treatment such that after it has been located at the target area within a patient subjecting it to a further treatment will cause the stent to become radioactive.

According to a more specific first embodiment of the first aspect of the invention the first treatment involves depositing on the surface of the stent an antigen or an antibody or a number of antigens or antibodies and the second treatment involves introducing into the patient's bloodstream a radioactive antibody or antigen respectively so that when the second treatment comes into contact with the first treatment the stent will become radioactive.

Because of the multiple antigens or antibodies on the stent surface there is the opportunity to treat the patient many times with radioactive antigens or antibodies.

According to a more specific second embodiment of the second aspect of the present invention the first treatment comprises making the stent magnetic and the second treatment comprises introducing into the patient's bloodstream a fluid which is both radioactive and magnetic so that when the fluid passes in contact with the stent radioactive material will be attracted to the stent to thereby make the stent itself radioactive.

In connection with the prior art approaches referred to earlier, it is known that beta or gamma radiation delivered locally within the lurnen of a coronary artery can reduce the incidence of restenosis.

An example of an antigen is a random peptide sequence and an example of an antibody is an immunoglobulin-gamma variety known as IgG or active pieces of these known as fragmented antibodies or Fabs.

The pharmacokinetics of these agents is known for example from Sharif et al; "Improving monoclonal antibody pharmacokinetics via chemical modification7; Quarterly Journal of Nuclear Medicine 1998, 42, 242-249.

It is also known for example to target or image liver metastases of colorectal cancer and bone marrow in humans by antibodies or Fabs "labelled" with radiation eg. 99 Tecnetium.

The key advantage of the present invention is that the application of radiation can be carried out completely physically separate from the earlier cardiovascular interventional procedure. This means that the first stage of introducing the stent into the patient can be carried out in the normal way in the normal catheter laboratory/theatre without introducing the added complication of the second stage of introducing the radioisotope into the patient. The latter stage can instead be carried out in the normal environment in which radiation therapy is currently given.

The key to providing this operational advantage is the provision of a stent which has a first treatment of the kind defined earlier. The stent could be of any known physical construction, although clearly some constructions of stent would be more amenable to the said first treatment of the present invention than others.

As indicated earlier, the way in which medical stents are normally used is to have them inserted into the patient's artery after an interventional procedure has been employed to restore the artery to substantially its original cross section, ie to increase its relatively restricted cross section. Examples of such interventional. procedures are those involving balloon catheters in which such a catheter is inserted into the patient and the balloon at its distal end is then expanded by means of a fluid, typically a saline solution, to press the tissue which is restricting the artery back into the wall of the artery. The stent would then be inserted into the target area, typically by being carried by the balloon catheter, and it would be left there permanently to, as it were, hold that part of the artery wall/tissue in the desired position.

According to a farther aspect of the present invention a stent is coated with an antigen in order to promote the production of antibodies within the patients blood in the vicinity of the stent.

How the invention may be carried out will now be described by way of example only and with reference to the accompanying drawings in which:

Figure I is a diagrammatic representation of a known construction of stent; Figure 2 is a cross-section taken on the line A-A of Figure I illustrating the coating on the stent; Figure 3 is a diagrammatic representation of a balloon catheter carrying a stent; Figure 4 illustrates the distal end of the balloon catheter carrying the stent at the target site within a patients vascular system; and Figure 5 is a flow diagram illustrating how the invention can be used to target radiation to an area within a patient A stent I is typically cylindrical or coiled and made of stainless steel. A known way of delivering the stent I to the target site within a patient's artery is to have it mounted on a balloon catheter 3 as illustrated in Figure 3. When the balloon catheter is radially expanded by the injection of a saline solution from the proximal end 3 a of the catheter the stent I is pressed into the wall of the patients artery in the target area in order to thereby increase the cross-sectional area of the artery and return it to substantially its original cross-section.

The position of the installed stent is iflustrated diagramatically in Figure 4, the artery being shown at 4.

Although the detailed construction of the stent is not critical from the point of view of the present invention and there are a wide variety of known constructions of stents, clearly there will be some constructions which lend themselves more easily to the application of the present invention than others.

A coronary stent 1 is introduced into the patient and has an antibody or an antigen attached to it. The patient having been discharged would then attend an oncology service where the antigen or antibody respectively with radioactive material attached, would be injected intravenously.

6 The antigen/antibody complex so formed at the stent site would induce the radiation to be localised to the area requiring treatment.

This concept alleviates all of the logistic problems associated with all the current concepts for radiation delivery in the cardiac catheter laboratory. Particularly there would be no need of radiation oncologists and physicists during the coronary intervention, nor would there be a requirement for delivery of materials or disposal of materials from the cardiac catheter laboratory. Likewise there would be no need for particular licensing for the radiation material to interventional suites.

The patient would be treated at the normal site for radiation therapy and would come under the care of the radiation oncologist under their site licenses etc.

Figure 5 is a flow diagram which shows how radiation can be targeted to an area within a patient.

The inventive concept of providing a coating to the stent I in order to promote a particular medically beneficial activity within a patients vascular system could be extended to the provision of a coating of any material on the stent which would provide such a beneficial effect.

I

Claims

1. A stent which has been subjected to a first treatment so that after it has been located at the target area within a patient and subjected to a further treatment causes the stent to become radioactive.

2. A stent as claimed in claim I in which the stent has deposited on its surface an antigen or antigens or an antibody or antibodies and the second treatment involves introducing into the patients bloodstream radioactive antibodies or antigens respectively so that when the second treatment comes into contact with the first treatment the stent will become radioactive.

I A stent as claimed in claim I in which the stent is rendered magnetic and the second treatment comprises introducing into the patients bloodstream a fluid which is both radioactive and magnetic so that when the fluid passes in contact with the stent radioactive material will be attracted to the stent to thereby make the stent itself radioactive.

4. A stent coated with an antigen in order to promote the production of antibodies within the patients blood in the vicinity of the stent when the stent has been inserted into a patients body.