WO1998046309A1

WO1998046309A1 - Double serial balloon catheter and method of prevention of restenosis

Info

Publication number: WO1998046309A1
Application number: PCT/US1998/007078
Authority: WO
Inventors: David W. Pipes; James J. Mazeika; Edward F. Smith, Iii
Original assignee: Mallinckrodt, Inc.
Priority date: 1997-04-17
Filing date: 1998-04-10
Publication date: 1998-10-22

Abstract

An angioplasty catheter having two balloons spaced longitudinally apart (double serial balloon catheter) is disclosed. The catheter is intended to allow both angioplasty and radiation treatment to be conducted with the single insertion of a single catheter. A method of sequentially performing coronary angioplasty and radiation of the angioplasty site with the single insertion of a double serial balloon catheter is also disclosed. The apparatus and method allow for the quick and convenient angioplasty and radiation treatment of stenosed arteries without the drawbacks associated with the insertion and withdrawal of two separate catheters.

Description

Double Serial Balloon Catheter and Method of Prevention of Restenosis

BACKGROUND OF THE INVENTION

This invention relates to a method of treating stenosis (blocked arteries) and preventing restenosis (re-blocking of the artery).

Percutaneous transluminal angioplasty (PTA) is the general technique of dilatation of a blocked artery (both peripheral and coronary (PTCA) arteries) with mechanical means at the end of a catheter. The use of a balloon catheter in PTA is well known. The catheter is positioned with the balloon at the site of the blockage, typically with the assistance of a guide wire and a fluoroscope, and the balloon inflated at high pressure (e.g.: 6 to 20 atmospheres (0.6 to 2 MPa). While the use of a balloon catheter in PTA is an effective technique, it is common for the affected artery to become re-blocked in a period of several (typically 3-6) months ("restenosis"). Restenosis is believed to occur as a result of injury to the arterial wall during the PTA procedure. One approach to restenosis is to repeat the PTA procedure. However, the expense of PTA and the inconvenience to the patient make this undesirable. Another approach is the use of a stent, which is a small, typically metal device that holds the artery open. Stents, however, are only partially effective in preventing restenosis. An approach that appears to be quite promising is the use of radiation to prevent restenosis. In doses of 8 to 30 Gy, radiation has been shown to be relatively safe and effective in preventing restenosis. While the exact mechanism of action is not known, it is suspected that the radiation "stuns" the cells that cause restenosis, rendering them less able to re-block the artery. Several approaches have been taken to supplying radiation to the affected site. One is the use of a solid radioactive source (such a beads) fixed in the end of a catheter. After PTA, the PTA catheter would be removed and the radioactive catheter inserted. This technique suffers from the disadvantage of making it difficult to center the radioactive source in the artery so that the artery is uniformly irradiated.

Another approach is to position guide wire past the obstruction, slide a balloon catheter over the guide wire to the obstruction, inflate the balloon to perform the angioplasty, remove the guide wire, and replace it with a wire having a radioactive tip. This approach suffers the disadvantages of difficulties centering the radiation source and problems associated with removing the guide wire, which may complicate response to a sudden collapse of the artery.

A technique that results in uniform irradiation is the use of a balloon catheter filled with a radioactive liquid. It is generally thought to be undesirable to use the same balloon catheter as used for the PTA procedure because that balloon has been subject to the stress of the PTA procedure and may be more likely to rupture. The consequence of a rupture would be the release of a radioactive liquid in the patient's blood stream. Thus, the approach deemed more desirable is to remove the PTA balloon catheter and to insert another balloon catheter for the radiation treatment. This, however, has the disadvantage of making the treatment time longer and involves another insertion of an object into the patient, increasing the risk of infection, etc. US 5,199,939 (Dake) teaches a general method of preventing restenosis by supplying a source of radiation at the end of a catheter to the affected vessel. Dake uses radioactive pellets at the end of a catheter having variable stiffness along its length. US 5,195,962 (Martin; Vas-Cath Incorporated) describes a catheter with 3 non-concentric lumens, and a method of manufacturing such a catheter. The central lumen of the catheter can be used for a guide wire. This reference discloses several other multi-lumen catheters. US 5,207,648 (Gross; The Kendall Company) describes a catheter with 3 concentric lumens.

US 5,226,889 (Sheiban) discloses a catheter having 2 balloons where the distal balloon is used to open an artery and the second, of larger diameter, is used to implant a stent. US 5,314,409 (Sarosiek; UVA Patents Foundation) teaches an esophageal perfusion catheter having two balloons and multiple lumens. Some of the lumens communicate with ports between the balloons.

US 5,342,306 (Michael) is representative of several disclosures that show two balloons used to isolate a treatment area in an artery so that liquid can be introduced into the space between the balloons without being washed away by blood flow.

WO 96/17654 (Thornton; Omnitron International) teaches the use of a balloon catheter filled with a radioactive liquid. In one embodiment Thornton uses multiple concentric balloons to guard against leakage, etc. In another embodiment Thornton uses a main balloon and two additional balloons on either side of the main balloon to block the flow in the artery in case of rupture of the main balloon, thus preventing flow of radioactive liquid throughout the patient's body.

SI JMMARY OF THE INVENTION

Briefly, the invention comprises an angioplasty catheter having two balloons spaced longitudinally apart (double serial balloon catheter). The catheter is intended to allow both angioplasty and radiation treatment to be conducted with the single insertion of a single catheter. The invention also comprises a method of sequentially performing coronary angioplasty and radiation of the angioplasty site with the single insertion of a double serial balloon catheter. The apparatus and method allow for the quick and convenient angioplasty and radiation treatment of stenosed arteries without the drawbacks associated with the insertion and withdrawal two separate catheters.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a perspective view of a catheter according to the invention.

Fig. 2 is a cross section of a catheter according to the invention.

Fig. 3 is a cross section of an alternative embodiment of the catheter of the invention.

Fig. 4 is a cross section of yet another alternative embodiment of the catheter of the invention.

DETAILED DESCRIPTION OF THE INVENTION

In this specification and claims, numerical values and ranges are not critical unless otherwise stated, that is, the numerical values and ranges may be read as if they were prefaced with the word "about" or "substantially".

The invention involves the use of a catheter having two longitudinally spaced balloons to open and radioactively treat an artery.

A catheter, according to the invention is shown in Fig. 1. Catheter 10 has a main shaft 12, a proximal end 14, and a distal end 16. As is shown in Fig. 2, main shaft 12 has an optional central lumen 20 intended to receive a guide wire. Central lumen 20 may run the entire length of catheter 10 (shown in

Fig. 1), or may extend only from the distal end to a portion somewhat midway along main shaft 12 (so-called monorail configuration). Main shaft 12 also has an angioplasty lumen 22 and a radiation lumen 24.

Fig. 3 shows a cross-section of an alternative construction of the catheter shaft in which main shaft 312 is made from 3 concentric tubes 321, 323, and 325, thus defining central lumen 320, angioplasty lumen 322, and radiation lumen 324. Of course, the function assigned to the three lumens may be changed so that, for instance, the central lumen may function as the radiation lumen.

Fig. 4 shows a cross-section of an alternative construction of the catheter shaft in which main shaft 412 is made from 3 attached tubes 421, 423, and 425, thus defining guide wire lumen 420, angioplasty lumen 422, and radiation lumen 424.

Referring again to Fig. 1, main shaft 12 has at its distal end angioplasty balloon 32 and radiation balloon 34, and at its proximal end, connector block 46. Angioplasty balloon 32 and radiation balloon 34 are spaced apart longitudinally along main shaft 12, with angioplasty balloon 32 more distal than radiation balloon 34. Although radiation balloon 34 could be more distal than angioplasty balloon 32, this would mean that radiation balloon 34 would have to pass through the stenosed area before it had been opened by angioplasty balloon 32, risking damage to radiation balloon 34 that could result in a leak or radioactive material into the bloodstream of the patient. Thus, it is preferred that angioplasty balloon 32 be more distal than radiation balloon 34. For clarity of illustration, angioplasty balloon 32 and radiation balloon 34 are shown in an inflated state. Connector block 46 has a wire port 40 which connects to central lumen 20 and is adapted to allow a guide wire to pass through catheter 10. Connector block 46 also has an angioplasty port 42 and a radiation port 44. Angioplasty lumen 22 fluidly connects angioplasty port 42 to angioplasty balloon 32. Similarly, radiation lumen 24 fluidly connects radiation port 44 to radiation balloon 34.

Catheter 10 and its parts may be constructed of conventional materials by conventional processes well known to those skilled in the art, including by the use of the materials and processes described in the patents listed above, the disclosures of which are hereby incorporated by reference.

The method of the invention begins with the insertion of the above- described catheter 12 into a stenosed (blocked) artery of a mammalian patient, preferably a human patient. Catheter 12 is preferably (but optionally) advanced over a previously positioned guide wire (not illustrated) which passes through central lumen 20 and out through wire port 40. When catheter 10 is advanced to the point that angioplasty balloon 32 is centered in the stenosed area of the artery, fluid pressure is applied through angioplasty port 42, through angioplasty lumen 22, to inflate angioplasty balloon 32. The inflation procedure is conventional and the fluid pressure may be provided, for instance, by depressing the plunger of a syringe filled with a liquid such as saline or an X-ray contrast agent. The use of an X-ray contrast agent to provide the fluid pressure is preferred because its use, in connection with a fluoroscope, will aid in determining whether the stenosis has been fully dilated.

After the angioplasty is complete, angioplasty balloon 32 is deflated by withdrawing the fluid through angioplasty lumen 22 and angioplasty port 42. Catheter 10 is then advanced through the artery until radiation balloon 34 is at the site of the corrected stenosis.

Once radiation balloon 34 is in place, it is inflated with a radioactive fluid through radiation port 44 and radiation lumen 24. Unlike the angioplasty portion of the procedure, where high pressures (typically 0.6 to 2 MPa) are needed to open the stenosed artery, the radiation portion of the procedure requires only enough pressure to fully inflate radiation balloon (typically 0.1 to 0.4 MPa). However, as with the angioplasty procedure, the fluid pressure may be provided, for example, by depressing a syringe. The radioactive fluid is preferably a liquid (e.g., a solution) that emits primarily medium to high strength beta radiation (e.g., 0.6 to 2.3 MeV (6.4 x 10¹² to 24.4 x 10¹² J), such as a solution containing Sm-153, Re-186, P-32, Re-188, or Y-90. After the radioactive fluid has inflated radiation balloon 34, catheter 10 is maintained in its position in the artery with radiation balloon 34 inflated for a sufficient time to provide a therapeutic dose of radiation to the previously stenosed artery. By "therapeutic dose of radiation" is meant sufficient radiation to reduce the incidence or severity of restenosis, but not so much as to cause substantial necrosis of the artery or surrounding organs.

Because radiation balloon 34 will block the flow of blood in the artery, it is desirable to use a radioactive fluid that is sufficiently radioactive that a therapeutic dose can be delivered in a relatively short period of time, for instance, less than 3 minutes. Alternatively, radiation balloon 34 can be inflated with a radioactive fluid for several minutes, deflated for a time to allow blood flow to resume, and thereafter reinflated to complete the dose. For very weak radioactive fluids this cycle may have to be repeated several times. Another alternative is to employ a bypass lumen (not illustrated) that will allow blood to flow from one side of an inflated balloon to the other through catheter 12. The use of bypass lumens is well known in the art.

Once a therapeutic dose of radiation has been delivered to the previously stenosed area, the radiation balloon is deflated by withdrawing the radioactive fluid through radiation lumen 24 and radiation port 44. Catheter 10 can then be withdrawn from the patient. EXAMPLE 1 (Hypothetical Example) A catheter generally resembling a Mallinckrodt® Vantage® peripheral dilation catheter is prepared; the notable difference being that the specially- prepared catheter has, in addition to the guide wire lumen and single balloon and its associated lumen, an additional balloon and associated lumen. An incision is prepared in the femoral artery of a human patient and with the assistance of a fluoroscope, a guide wire is positioned past a stenosed site in the femoral artery. The specially-prepared catheter is fed onto the guide wire and advanced into the femoral artery of the patient. The catheter is advanced further until the most distal balloon is at the site of the stenosis. Diluted Hexabrix® X-ray contrast media (from Mallinckrodt Medical, Inc.) is forced out of the inflator syringe by hand to inflate the balloon to 1.5 MPa, opening the artery. The balloon is then deflated to allow the catheter to be repositioned. The catheter is then advanced further until the second balloon is at the site of the former stenosis. Mallinckrodt® MP-2343 sodium perrhenate Re- 186 solution (activity = 250 mCi/ml (9250 MBq/ml) is forced by hand to inflate the second balloon to 0.2 MPa. The second balloon, having a volume of 0.25 ml, remains inflated and in position for 5 minutes, delivering a dose of 15 Gy (at 0.5 mm depth) to the artery. The second balloon is deflated by withdrawing the plunger of the syringe. The catheter is then withdrawn from the patient, followed by withdraw of the guide wire.

Claims

What is claimed is:

1. A double serial balloon catheter for sequential balloon angioplasty and liquid-filled balloon radiation, comprising

(a) a catheter member having a proximal end and a distal end, said catheter member defining an angioplasty lumen and a radiation lumen, each of said lumens connecting the proximal end to the distal end of the catheter member;

(b) an angioplasty balloon positioned at the distal end of and coaxial with said catheter member, said angioplasty balloon being fluidly connected to the angioplasty lumen of said catheter member; and

(c) a radiation balloon positioned at the distal end of and coaxial with said catheter member, said radiation balloon being fluidly connected to the radiation lumen of said catheter member and being longitudinally displaced along the length of said catheter member from said angioplasty balloon.

2. The double serial balloon catheter of claim 1 wherein said angioplasty balloon is more distal than said radiation balloon.

3. The double serial balloon catheter of claim 1 wherein between said angioplasty balloon and said radiation balloon there is no communication between any lumen of said catheter and the outside of said catheter.

4. The double serial balloon catheter of claim 1 wherein said catheter additionally defines a guide-wire lumen.

5. The double serial balloon catheter of claim 4 wherein the guide wire lumen is centrally located within said catheter.

6. A method of sequentially performing coronary angioplasty and radiation of the angioplasty site in a mammal patient, comprising:

(a) inserting a catheter into an artery of the patient, the catheter comprising a double serial balloon catheter having

(i) a catheter member having a proximal end and a distal end, said catheter member defining an angioplasty lumen and a radiation lumen, each of said lumens connecting the proximal end to the distal end of the catheter member;

(ii) an angioplasty balloon positioned at the distal end of and coaxial with said catheter member, said angioplasty balloon being fluidly connected to the angioplasty lumen of said catheter member; and

(iii) a radiation balloon positioned at the distal end of and coaxial with said catheter member, said radiation balloon being fluidly connected to the radiation lumen of said catheter member and being longitudinally displaced along the length of said catheter member from said angioplasty balloon;

(b) positioning the angioplasty balloon at a site to be treated;

(c) inflating the angioplasty balloon via the angioplasty lumen;

(d) deflating the angioplasty balloon;

(e) positioning the radiation balloon at the site to be treated; (f) inflating the radiation balloon via the radiation lumen with a radioactive fluid;

(g) deflating the radiation balloon; and

(h) withdrawing the catheter from the patient.

7. The method of claim 6 wherein the radioactive fluid is a radioactive liquid.

8. The method of claim 7 wherein the radioactive liquid is a solution containing a dissolved radioactive solid.

9. The method of claim 6 wherein the radiation balloon is inflated for a time sufficient to deliver a therapeutic dose of radiation.

10. The method of claim 6 wherein the radiation balloon is inflated for a first period of time, deflated to allow blood flow to resume, and thereafter reinflated for a second period of time to expose the site to be treated to additional radiation.

11. The method of claim 6 wherein the patient is a human.

12. The method of claim 6 wherein the catheter is inserted into the patient over a guidewire.