WO2014137977A1

WO2014137977A1 - Magnetic targeting device with balloon

Info

Publication number: WO2014137977A1
Application number: PCT/US2014/020122
Authority: WO
Inventors: Robert J. Levy
Original assignee: Childrens Hospital of Philadelphia CHOP
Current assignee: Childrens Hospital of Philadelphia CHOP
Priority date: 2013-03-06
Filing date: 2014-03-04
Publication date: 2014-09-12
Anticipated expiration: 2015-09-06

Abstract

A magnetic targeting device includes a catheter portion, a catheter balloon fluidly connected to the catheter portion, and a mesh surrounding the catheter balloon. The catheter balloon can be an angioplasty balloon. In addition, the catheter balloon can be a high pressure balloon formed of a non-compliant or low compliant material. The mesh can be formed of a magnetizable material, including but not limited to 304 stainless steel wire, 430 stainless steel wire, or other stainless steels that are magnetizable.

Description

MAGNETIC TARGETING DEVICE WITH BALLOON

RELATED APPLICATION

This application claims the benefit of priority of U.S. Provisional Application No. 61/773,288, filed March 6, 2013, the content of which is incorporated by reference herein in its entirety and for all purposes.

FIELD

This invention relates generally to therapeutic treatment of humans and animals, and more specifically to a system and method for delivering therapeutic compounds using a magnetic targeting device that features at least one balloon.

BACKGROUND

Medical procedures have been developed that utilize magnetic nanoparticles (MNP) to treat various diseases and conditions, these medical procedures being the subjects of prior patents and patent applications assigned to the applicant, including but not limited to U.S. Patent No. 7,846,201, U.S. Application Publication No. 2009/0216320, U.S.

Application Publication No. 2009/0082611, U.S. Application Publication No.

2010/0260780, International Application Publication No. WO 2004/093643, International Application Publication No. WO 2012/061193, U.S. Provisional Application No. 61/410,156 and U.S. Provisional Application No. 61/481,447, the contents of which are incorporated by reference herein in their entireties and for all purposes (hereinafter, the "Incorporated References"). The feasibility of magnetic targeting procedures has been demonstrated for delivering drugs, gene vectors and cell therapy.

Some of the medical devices and procedures in the Incorporated References can be used to target magnetically responsive nanoparticles (hereinafter, referred to collectively as "MNP") to an area of the body in need of treatment. The MNP, which contain therapeutic agents, can be targeted to one or more permanently deployed stents in vivo. Alternatively, the MNP can be targeted to a magnetic targeting device temporarily placed in the body.

In some instances, there is a need to perform magnetic targeting of MNP in conjunction with other procedures. The medical devices described in the Incorporated References are not designed to perform medical procedures other than magnetic targeting of MNP, however.

SUMMARY

In one beneficial aspect of the invention, a magnetic targeting device includes a catheter portion, a catheter balloon fluidly connected to the catheter portion, and a mesh surrounding the catheter balloon.

In another beneficial aspect of the invention, the catheter balloon may be an angioplasty balloon.

In another beneficial aspect of the invention, the catheter balloon may be a high pressure balloon formed of a non-compliant or low compliant material.

In another beneficial aspect of the invention, the mesh may be formed of a magnetizable material.

In another beneficial aspect of the invention, the mesh may be formed of 304 stainless steel wire, 430 stainless steel wire, or other stainless steels that are

magnetizable.

In another beneficial aspect of the invention, the mesh may be a braided mesh that defines a plurality of pores, each pore having a pore size.

In another beneficial aspect of the invention, the pore size of the pores may be between about 250 microns and about 2000 microns.

In another beneficial aspect of the invention, the catheter balloon and the mesh may be radially expandable from a radially retracted state to a radially expanded state.

In another beneficial aspect of the invention, the mesh may radially expand to the expanded state in response to radial expansion of the catheter balloon inside the mesh.

In another beneficial aspect of the invention, an outer shaft may be operably connected with the mesh, the outer shaft being axially displaceable between a first axial position to radially expand the mesh and a second axial position to radially contract the mesh.

In another beneficial aspect of the invention, the catheter portion may include a hollow inner shaft and a hollow outer shaft that surrounds and contains at least a portion of the hollow inner shaft.

In another beneficial aspect of the invention, the inner shaft may define a first lumen for containing a guidewire.

In another beneficial aspect of the invention, the inner shaft may comprise a second lumen in fluid communication with the catheter balloon.

In another beneficial aspect of the invention, a distal occlusion balloon may be coupled to the catheter portion.

In another beneficial aspect of the invention, the inner shaft may include a third lumen in fluid communication with the distal occlusion balloon.

In another beneficial aspect of the invention, the inner shaft may include a fourth lumen defining a flush channel.

In another beneficial aspect of the invention, a proximal occlusion balloon may be coupled to the catheter portion.

In another beneficial aspect of the invention, the outer shaft may define a primary lumen and a secondary lumen, at least a portion of the inner shaft being disposed in the primary lumen.

In another beneficial aspect of the invention, the inner shaft and outer shaft may define an annular space between the inner shaft and outer shaft. In another beneficial aspect of the invention, the outer shaft may define at least one port at a distal end of the outer shaft.

In another beneficial aspect of the invention, at least one port may be adjacent to the mesh.

In another beneficial aspect of the invention, at least one port may be positioned on the catheter portion between the distal occlusion balloon and the mesh.

In another beneficial aspect of the invention, at least one port may define an injection port configured to release MNPs.

In another beneficial aspect of the invention, the mesh may be expandable to a relatively expanded state, and the catheter balloon may be expandable to an intermediate expanded state in the catheter balloon, the mesh and catheter balloon being separated by a narrow plenum space between the mesh and the catheter balloon.

In another beneficial aspect of the invention, a method of treating a medical condition in a human or animal with one or more therapeutic agents includes the steps of: a) advancing a catheter to a treatment site in the human or animal, the catheter comprising a catheter balloon and a magnetizable mesh surrounding the catheter balloon; b) establishing a uniform magnetic field at the treatment site; c) releasing a plurality of MNP containing the one or more therapeutic agents from the catheter to a location near the mesh in the uniform magnetic field, the MNPs comprising one or more magnetic field- responsive agents; d) radially expanding the catheter balloon and the mesh until the mesh contacts the treatment area; and e) maintaining the uniform magnetic field after the step of releasing the plurality of MNP to draw the MNP to the mesh and into contact with the treatment area.

In another beneficial aspect of the invention, step a) may include the step of advancing the catheter into an obstructed or partially obstructed area of an artery.

In another beneficial aspect of the invention, step d) may include the step of radially expanding the catheter balloon and mesh to open the obstructed or partially obstructed area of the artery in an angioplasty procedure.

In another beneficial aspect of the invention, the method may include the step of radially retracting the catheter balloon after step d) to create a narrow plenum space between the catheter balloon and the wall of the artery.

In another beneficial aspect of the invention, the method may include the step of retracting the catheter balloon so that the catheter balloon is spaced from the wall of the artery by an average distance of about 1 millimeter.

In another beneficial aspect of the invention, the method may include the step of, before step c), inflating a first occlusion balloon located on the catheter to temporarily occlude the artery and limit blood flow past the treatment site.

In another beneficial aspect of the invention, the method may include the step of, before step c), inflating a second occlusion balloon located on the catheter to temporarily occlude the artery and limit blood flow past the treatment site, the first occlusion balloon and second occlusion balloon defining an inter-occlusion balloon space between the first and second occlusion balloons.

In another beneficial aspect of the invention, the method may include the step of deflating the second occlusion balloon approximately two minutes after the step of inflating the second occlusion balloon to at least partially restore blood flow in the artery.

In another beneficial aspect of the invention, the method may include the step of deflating the first occlusion balloon approximately two minutes after the step of inflating the first occlusion balloon to at least partially restore blood flow in the artery.

In another beneficial aspect of the invention, step e) may include the step of maintaining the uniform magnetic field for a total exposure time of t₂ minutes, wherein t₂ is between about 25 minutes and about 30 minutes.

In another beneficial aspect of the invention, the method may include the step of retracting the catheter balloon to a relatively retracted state after step e).

In another beneficial aspect of the invention, the method may include the step of retracting the mesh to a relatively retracted state after step e).

In another beneficial aspect of the invention, the method may include the step of removing the catheter from the human or animal after step e).

In another beneficial aspect of the invention, the method may include the step of moving the catheter to another treatment site in the human or animal after step e).

In another beneficial aspect of the invention, the method may include the steps of inflating first and second occlusion balloons and aspirating the inter-occlusion balloon space before step c).

In another beneficial aspect of the invention, the method may include the step of establishing a uniform magnetic field of 0.1T.

In another beneficial aspect of the invention, the method may include the step of capturing the released MNP in the mesh as the mesh is expanded through the MNP to move the MNP toward the arterial wall.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing summary and the following detailed description may be better understood in conjunction with the drawing figures, of which :

Figure 1 is a perspective view of a kit in accordance with one exemplary embodiment of the invention, the kit including a magnetic targeting device;

Figure 2 is a magnified perspective view of the magnetic targeting device of Figure

1, the device schematically shown in a first operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 3 is a magnified perspective view of the magnetic targeting device of Figure 1, the device schematically shown in a second operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 4 is a magnified perspective view of the magnetic targeting device of Figure 1, the device schematically shown in a third operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 5 is a magnified perspective view of the magnetic targeting device of Figure 1, the device schematically shown in a fourth operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 6 is a magnified perspective view of the magnetic targeting device of Figure 1, the device schematically shown in a fifth operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 7 is a magnified perspective view of the magnetic targeting device of Figure 1, the device schematically shown in a sixth operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 8 is a magnified perspective view of the magnetic targeting device of Figure 1, the device schematically shown in a seventh operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 9 is a magnified perspective view of the magnetic targeting device of Figure 1, the device schematically shown in a eighth operative state in a blood vessel, the device shown truncated with a section broken away;

Figure 10 is a magnified cross-section view of the magnetic targeting device of Figure 1 taken through line 10-10 in Figure 1 ;

Figure 11 is a magnified truncated cross-section view of the magnetic targeting device in Figure 1, showing features at the proximal end of the device in a first operative state;

Figure 12 is a magnified truncated cross-section view of the magnetic targeting device in Figure 1, showing features at the proximal end of the device in a second operative state;

Figure 13 is a view of a magnetic targeting device in accordance with another exemplary embodiment of the invention;

Figure 14 is a block flow diagram of a treatment method in accordance with another exemplary embodiment of the invention; and

Figure 15 is a block flow diagram of a treatment method in accordance with another exemplary embodiment of the invention.

DETAILED DESCRIPTION

Although the invention is illustrated and described herein with reference to specific embodiments, the invention is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the invention.

Medical devices and methods in accordance with the invention are capable of performing VMI procedures in combination with other medical procedures. In one embodiment, a magnetic targeting device includes a wire mesh and a balloon integrated with the wire mesh. The balloon is arranged inside the wire mesh. The balloon and mesh can be expanded and retracted simultaneously, or independently at different times.

Magnetic targeting devices that feature balloons in accordance with the invention can be used to perform both an angioplasty procedure and a VMI procedure within a diseased artery. If desired, the devices can be used initially to perform an angioplasty, and be used subsequently to perform a VMI procedure immediately after the angioplasty. An angioplasty procedure and VMI procedure can both be performed with a single device in accordance with the invention. Where a catheter is used, only one catheterization procedure needs to be performed to complete both the angioplasty procedure and the VMI procedure. This avoids having to perform two separate catheterization procedures in order to complete the angioplasty procedure and the VMI procedure. A single

interventional procedure for treating a critically obstructed artery has a number of advantages over a two procedure approach, including the following: 1) reduced risk of vasospasm, which can occur with increased arterial manipulations (treatment of vasospasm even further prolongs procedures with potential adverse drug effects); 2) reduced probability of thrombo-embolic complications with a single procedure versus two steps; and 3) decreased operative/anesthesia times— associated with lower infection risks and a more rapid recovery.

Devices, systems and methods of the invention can be used for delivering MNP comprising a therapeutic agent to catheter-accessible sites in a human or animal subject. Various medical conditions may be treated in this manner. For example, various pathologic conditions may be treated, such as arterial disease and other disorders presently treated by stent intervention, including urologic diseases, conditions requiring bronchial stents, and gastrointestinal conditions treated by stent deployment, such as the use of bile duct stents. For simplicity, the following description will focus mainly on devices, systems and methods for treatment of arterial diseases. It will be understood that devices, systems and methods in accordance with the invention can be used to treat many different sites, and many different diseases and conditions, in a human or animal subject.

The devices, systems and methods of the invention may feature a magnetic targeting device having a design suited for temporary placement in an artery or other site in need of treatment. In a preferred embodiment, the magnetic targeting device includes a catheter and an expandable wire mesh, the mesh being integral with or permanently affixed to the catheter. Devices, systems and methods of the invention may also feature a plurality of MNP. As an alternative to MNP, the devices, systems and methods of the invention may deliver cells loaded with MNP.

Devices, systems and methods of the invention may further include a magnetic filter that can be used at a location "downstream" of the magnetic targeting device to trap and remove non-targeted MNP. As used herein, the term "non-targeted" refers to magnetic nanoparticles that have escaped capture by the magnetic targeting device and arterial wall. The filter may be a component that is completely separate from the magnetic targeting device, or a component of the magnetic targeting device, as will become apparent in the examples that follow.

Furthermore, devices, systems and methods of the invention may include one or more occlusion balloons designed to temporarily occlude an artery and limit flow in the artery while the MNP are targeted to the arterial wall. Limiting flow in the artery can reduce "washout," which occurs when arterial flow pulls MNP or cells from the arterial wall after the MNP or cells reach the arterial wall. Reducing washout enhances MNP and cell retention in the targeted arterial segment. Like the filter, the occlusion balloons may be completely separate from the magnetic targeting device, or a component of the magnetic targeting device.

Excellent targeting and retention is possible using a magnetic targeting device containing superparamagnetic material (e.g., 304, 420, 430 stainless steel, and others). In addition to using superparamagnetic material, excellent targeting and retention is possible with MNP having affinity-surface modification to increase adhesion to arterial walls (or to tissues at other targeted sites, such as bile ducts). The magnetic targeting device may be manufactured using a common commercially available catheter, a custom made catheter, various types of probes, or other types of medical devices configured for insertion into a human or animal.

Devices in accordance with the invention may be used to treat locations within a diseased artery. The locations may have been previously stented or may still contain a stent. Once the magnetic targeting device is passed through the artery to the treatment site, a uniform magnetic field is applied to the treatment site for a period of time sufficient to provide good capture of MNP at the site.

Various parts of devices in accordance with the invention will be described herein using the terms "proximal" and "distal." The term "proximal," as defined herein, means "in the direction of the medical professional," and the term "distal," as defined herein, means "in the direction of the patient." When referring to specific features of the magnetic targeting device, the terms refer to the relative position of the feature (e.g. toward the medical professional or toward the patient) when the device is inserted in the patient as intended to perform a magnetic targeting procedure. Systems in accordance with the invention may be packaged, sold and/or distributed in the form of a kit. Referring now to Figure 1, a kit 100 is shown in accordance with one exemplary embodiment of the invention. Kit 100 includes a magnetic targeting device 600, a plurality of MNP 700 in a suspension to be administered through the magnetic targeting device, and a magnetic field source 800 for generating a uniform magnetic field. Magnetic field source 800 may include one or more pairs of permanent magnets or electromagnets.

As noted above, magnetic targeting devices in accordance with the invention may include a balloon integrated into the magnetic targeting device. The balloon may be formed of a number of materials and serve one or more functions. Where the magnetic targeting device includes a catheter, the balloon may be referred to herein as a "catheter balloon."

In some embodiments of the invention, the catheter balloon may serve solely as a "dead space balloon." The term "dead space balloon," as used herein, is defined as a balloon that is inflated in the artery to occupy some of the space around the catheter between the catheter and the arterial wall. As will be discussed, the inflation of a dead space balloon around the catheter decreases the volume of space around the catheter, which decreases the volume of space through which the MNP need to travel, thereby guiding the MNP more quickly to the arterial wall. Dead space balloons may be

constructed of compliant or non-compliant materials, and can be inflated using relatively low pressure or relatively high pressure.

In other embodiments of the invention, the catheter balloon can be used as a dead space balloon, and to perform an angioplasty procedure. Balloons that serve both purposes will be referred to herein as "angioplasty balloons." Angioplasty balloons in accordance with the invention can be selected from commercially available balloon products or materials. The material used in angioplasty balloons is preferably a non- compliant material that is configured to expand under higher pressures.

Referring now to Figure 2, magnetic targeting device 600 is shown in more detail. The double arrow at the top of Figure 2 indicates a first direction labeled "PROX" to indicate the proximal direction, and a second direction labeled "DIST" to indicate the distal direction.

Magnetic targeting device 600 includes a combination angioplasty-magnetic targeting catheter 602. Catheter 602 includes an inner shaft 610 comprising a proximal end 612, a distal end 614, and a hollow body 613 extending between the proximal end and distal end. Catheter 602 further includes an outer shaft 660 extending over at least a portion of the inner shaft 610. Outer shaft 660 includes a proximal end 662, a distal end 664, and a hollow body 663 extending between the proximal end and distal end. Inner shaft 610 and outer shaft 660 contain a number of lumens extending through the inner shaft from the proximal end to the distal end, as will be described in more detail below.

Magnetic targeting device 600 includes a catheter balloon 620 and an expandable mesh 630 surrounding the catheter balloon. Catheter balloon 620 is an angioplasty balloon integrated with catheter 602. As such, catheter balloon 620 is designed to perform an angioplasty procedure, and designed to reduce the volume of space during a VMI procedure.

Catheter balloon 620 includes a balloon wall 622 surrounding an interior space 621. Balloon wall 622 is disposed around a distal portion of inner shaft 610, with the distal portion of the inner shaft having a port 616 in fluid communication with interior space 621 of the catheter balloon. A source of gas or liquid can be connected in fluid communication with inner shaft 610 and port 616.

Expandable mesh 630 has a proximal end 632 and a distal end 634, and is formed of a magnetizable material. Various mesh materials may be used for the mesh in accordance with the invention. Mesh 630 is formed of braided strands 635 made of 304 stainless steel wire. One suitable 304 stainless steel mesh is a braided mesh

manufactured by US Biodesign of Perkasie, Pennsylvania, USA. Unlike some wire mesh materials, a braided wire mesh made of 304 stainless steel wire offers the advantage of providing a mesh that is very flexible, making the mesh compatible with placement around a dead space balloon or angioplasty balloon. The flexibility of the braided mesh allows the mesh to smoothly and uniformly expand as the balloon inside the mesh expands. A braided wire mesh made of either 304 or preferably 430 stainless steel wire can also provide a mesh material that naturally expands radially outwardly on its own. The braided mesh exhibits some degree of shape memory and elasticity when the mesh is retracted or collapsed. The shape memory and elasticity returns the mesh to at least a partially expanded state when the forces retracting the mesh are removed. This tendency to expand can assist with maintaining the mesh in contact with an arterial wall to target MNP to the arterial wall.

Magnetic targeting device 600 also includes a pair of integrated occlusion balloons adapted to inflate and constrict a section of a vessel surrounding the catheter. A first occlusion balloon 640 is located proximally with respect to expandable mesh 630, and a second occlusion balloon 650 is located distally with respect to the expandable mesh. First occlusion balloon 640 can be inflated with a gas or liquid to constrict the artery at a location upstream from the treatment site and temporarily stop the flow of blood to the treatment site. Similarly, second occlusion balloon 650 can be inflated to constrict the artery at a location downstream from the treatment site and temporarily stop the flow of blood from the treatment site. First and second occlusion balloons 640 and 650 are independently operable to control flow through the artery past the treatment site, and one may be inflated while the other is deflated, if the need for such operation arises. When first and second occlusion balloons 640 and 650 are both inflated to constrict the artery, flow to and from the treatment site is halted, creating a static condition. In the static condition, a suspension of MNP can be administered to the treatment site and targeted to the vessel wall under a uniform magnetic field. The static condition minimizes the potential for MNP being pulled into the bloodstream and carried away from the treatment site.

Referring to Figure 10, various lumens in inner shaft 610 and outer shaft 660 will be described. Outer shaft 660 defines a primary lumen 665 and a secondary lumen 667. Primary lumen 665 and secondary lumen 667 extend from the proximal end 662 to distal end 664 of outer shaft 660. Primary lumen 665 is offset from the central longitudinal axis of outer shaft 660, as shown. Inner shaft 610 extends through primary lumen 665. A first lumen 611, second lumen 615, third lumen 617 and fourth lumen 619 extend through inner shaft 610.

The catheter balloon 620, first occlusion balloon 640 and second occlusion balloon

650 are fluidly operated by the various lumen extending through inner shaft 610 and outer shaft 660. Specifically, first lumen 611 receives and holds a guidewire 670 that is passed through magnetic targeting device 600. Second lumen 615 connects in fluid communication with catheter balloon 620, and can be used to inflate and deflate the catheter balloon. Third lumen 617 connects in fluid communication with the second

(distal) occlusion balloon 650, and can be used to inflate and deflate the second occlusion balloon with a gas or liquid. Fourth lumen 619 defines a channel for aspirating or flushing the treatment area as required.

Primary lumen 665 serves a number of functions. First, it contains inner shaft 610, as noted above. Primary lumen 665 also provides a conduit for delivering MNP to the treatment site. In this regard, primary lumen 665 passes through outer shaft 660 and exits the outer shaft through a discharge port 668 at the distal end 664 of the outer shaft adjacent to mesh 630. Discharge port 668 is configured to release MNP into the treatment area where the MNP can be directed toward the target area. Primary lumen 665 further provides an annular channel that can be used to flush fluid from the treatment area. For example, when the first and second occlusion balloons 640 and 650 are inflated, fluid within the "inter-occlusion balloon space" S, i.e. the space between the inflated occlusion balloons, can be flushed out through primary lumen 665.

Secondary lumen 667 connects in fluid communication with first occlusion balloon 640, and can be used to inflate and deflate the first occlusion balloon with a gas or liquid.

Mesh 630 is operable in a fully retracted or collapsed condition (see e.g., Figure 2), a partially expanded condition (see e.g., Figure 6) or a fully expanded condition (see e.g., Figure 7). In the fully retracted condition, mesh 630 is positioned in relative proximity to inner shaft 610. This retracted condition keeps the outer extremity of expandable mesh 630 away from a vessel wall V so that magnetic targeting device 600 can be maneuvered more easily through the vessel . In the fully expanded condition, mesh 630 extends radially outwardly from inner shaft 610, in relative proximity to or in contact with vessel wall V.

Distal end 664 of outer shaft 660 is connected with proximal end 632 of

expandable mesh 630. Expansion and retraction of mesh 630 is mechanically controlled by adjusting the axial position of outer shaft 660 relative to inner shaft 610. Outer shaft 660 is axially displaceable in a proximal direction relative to inner shaft 610 to move mesh 630 to the fully retracted condition. Outer shaft 660 is also axially displaceable in a distal direction relative to inner shaft 610 to move mesh 630 to the fully expanded condition. As such, outer shaft 660 can be "pushed" in a distal direction relative to inner shaft 610 to expand mesh 630, and "pulled" in a proximal direction relative to the inner shaft to retract the mesh.

Various mechanisms can be used to expand and retract mesh 630. Referring to

Figures 11 and 12, magnetic targeting device 600 features an integrated control handle 680. Control handle 680 includes a handle body 682 forming an inner chamber 684 that receives inner shaft 610, outer shaft 660 and guidewire 670. A slide member 686 is slidably displaceable in chamber 684 and fixed to the proximal end 662 of outer shaft 660. A thumb pad or button 688 is attached to slide member 686 through a slot 683 that extends through handle body 682. Outer shaft 660 is slidably displaceable over inner shaft 610 in response to sliding movement of button 688 relative to handle body 682. Button 688 is moveable to a distal position, shown in Figurel l, to push outer shaft 660 in the distal direction and place mesh 630 in the expanded state. Button 688 is further moveable to a proximal position, shown in Figure 12, to pull outer shaft 660 in the proximal direction and place mesh 630 in a retracted state.

Referring now to Figure 13, a magnetic targeting device 800 is shown in

accordance with another exemplary embodiment. Magnetic targeting device 800 is more or less the same device as magnetic targeting device 600, including all of the same components, but utilizing a different control handle 880. Control handle 880 includes a slidable knob 882. Knob 882 is moveable in a distal direction relative to the control handle to push the outer shaft in a distal direction and place the mesh in the expanded state. Knob 882 is further moveable in a proximal direction relative to the control handle to pull the outer shaft in the proximal direction and place the mesh in a retracted state.

Control handles that feature a sliding knob or button in accordance with the invention preferably have a limited stroke distance, i.e. a maximum distance through which the knob or button can slide on the handle. This limits how far the inner shaft can be extended relative to the outer shaft so that components like the mesh are not overstretched. Knob 882, for example, has a maximum stroke distance of 1.0 inch.

Control handles that feature a sliding knob or button in accordance with the invention also preferably include a retention mechanism that holds the relative position of the knob or button when the knob or button moves the mesh to a fully expanded condition or a fully retracted condition. Control handle 880, for example, includes a first O-ring (not shown) that frictionally holds knob 882 when it is advanced to a position that fully expands the mesh, and a second O-ring (not shown) that frictionally holds the knob when it is advanced to a position that fully retracts the mesh.

Figure 13 also shows various lumens connected to magnetic targeting device 800.

These lumens, which could also be connected to device 600, include a lumen 702 for a guidewire, a lumen 704 in fluid communication with the annular space between the inner and outer shafts, a lumen 706 in fluid communication with the proximal occlusion balloon, a lumen 708 in fluid communication with the distal occlusion balloon, and a lumen 710 in fluid communication with the catheter balloon. Each lumen is preferably identified and differentiated from other lumens by a label bearing some unique identifier, which may be in the form of a color coded label, a label containing written indicia, or other types of identification.

Referring now to Figure 14, a general method 1000 for performing a VMI procedure in accordance with an exemplary embodiment of the invention is summarized in a block flow diagram. A magnetic targeting device with a balloon is inserted into a human or animal and advanced to a treatment area in step 1010. The device includes a

magnetizable mesh that surrounds the balloon. The balloon is radially expanded in step 1020 to radially expand the balloon wall and mesh toward the arterial wall . As the balloon expands, the balloon wall bears radially outwardly against the mesh, forcing the mesh to also expand radially outwardly with the balloon. The balloon and mesh are expanded in unison until both contact or lie adjacent to the obstruction on the arterial wall. A uniform magnetic field is then applied to the treatment area in step 1030. A plurality of MNP are released into the treatment area from the device in step 1040. The uniform magnetic field magnetizes the mesh, which draws the MNP toward the arterial wall.

General method 1000 outlines basic steps for performing a VMI procedure in accordance with one exemplary embodiment of the invention. Additional steps not specifically mentioned or shown in Figure 14 may also be performed. These additional steps may include performing an angioplasty procedure with the balloon and/or deploying additional components on the device, including but not limited to occlusion balloons.

Additional steps may also include partially or completely collapsing the balloon and mesh, removing the uniform magnetic field from the treatment area, and removing the magnetic targeting device from the treatment area. The steps shown in Figure 14 may be performed in the order shown, or may be performed in other sequences. For example, the step of applying the magnetic field in step 1030 appears after the step of expanding the balloon and mesh in step 1020. Step 1030 need not occur after step 1020, however, as it could also occur before step 1020, or simultaneously with step 1020. Similarly, step 1040 (releasing MNP) need not occur after 1030, but can be done before step 1030, or before step 1020. Therefore, the sequence of steps shown in Figure 14 represents only one possible sequence of steps. Other sequences of steps are possible and contemplated in accordance with the invention.

Referring now to Figure 15, a method 2000 for performing a combined angioplasty- VMI procedure in accordance with another exemplary embodiment of the invention is summarized in a block flow diagram. Method 2000 is described as it would be performed using magnetic targeting device 600.

Beginning with step 2010, a guidewire is inserted into the human or animal, and advanced to the treatment site in the artery. In step 2020, magnetic targeting device 600 is advanced over the guidewire and into the human or animal until the catheter reaches the treatment area (see e.g., Figure 2). All balloons on magnetic targeting device 600 are preferably deflated prior to advancing catheter 602 over the guidewire. In addition, mesh 630 is preferably collapsed prior to advancing the catheter over the guidewire. By deflating all balloons and collapsing the mesh, the profile of magnetic targeting device 600 is minimized so that the device can be advanced more easily through the artery.

Once magnetic targeting device 600 is positioned in the treatment area, a uniform magnetic field F is established at the site in step 2030 (see e.g., Figure 3). For example, a uniform magnetic field of 0.1T may be established. Next, in step 2040, the proximal occlusion balloon 640 is expanded, and then the distal occlusion balloon 650 is expanded (see e.g., Figure 4). Proximal occlusion balloon 640 and distal occlusion balloon 650 collectively form an inter-occlusion balloon space S in the artery, and blood flow is temporarily halted around the treatment area. In step 2050, blood is aspirated from inter-occlusion balloon space S. Once inter-occlusion balloon space S is aspirated, a solution of MNP 700 is injected from port 668 into the inter-occlusion balloon space in step 2060 (see e.g., Figure 5). Upon their release into inter-occlusion balloon space S, the MNP 700 are exposed to the uniform magnetic field F. The MNP 700 are targeted to the braided wires 635 of mesh 630.

Magnetic assays have shown that mesh captures MNP more effectively when the mesh is expanded through a suspension of MNP. Therefore, catheter balloon 620 and mesh 630 are preferably expanded in step 2070 into the suspension of MNP 700 while the MNP are being released into the inter-occlusion balloon space S, or shortly after the MNP 700 have been released into the inter-occlusion balloon space S (see e.g., Figure 6). As catheter balloon 620 and mesh 630 expand in unison, the catheter balloon and mesh capture the MNP 700 and position them against the arterial wall. Catheter balloon 620 is also expanded at this time to relieve the obstruction in an angioplasty procedure in step 2080.

Mesh 630 can be expanded radially outwardly toward the arterial wall by two different expansion mechanisms. First, mesh 630 can be expanded by axially displacing outer shaft 660 in a distal direction relative to inner shaft 610. Braided strands 635 of mesh 630 are formed of resilient material with a shape memory. Strands 635 naturally expand radially outwardly when in a relaxed state, due to the shape memory. When outer shaft 660 is moved in a distal direction relative to inner shaft 610, the axial length of mesh 630 is shortened. The shape memory of strands 635 causes the strands to readily expand radially outwardly as mesh 630 is shortened.

Mesh 630 can also be expanded radially outwardly by inflating catheter balloon 620 with a gas or liquid, A source of gas or liquid is connected with second lumen 615 in inner shaft 610 and opened to inflate catheter balloon 620. As catheter balloon 620 expands, wall 622 of the catheter balloon bears against mesh 630 and forces strands 635 to expand radially outwardly. Strands 635 spread apart from one another as mesh 630 expands, forming pores 636 between the strands. Pores 636 are relatively small openings, and may have dimensions ranging from about 250 microns to about 2,000 microns when mesh 630 is fully expanded. The pore size may be selected based on a number of parameters, including but not limited to the magnitude of magnetic forces, the relative size of MNP or cells being injected, and the amount of arterial wall access needed.

Both expansion mechanisms combine to expand mesh 630 until strands 635 contact the obstruction in the artery. Depending on the size of the obstruction, balloon 620 and mesh 630 may contact the obstruction in a partially expanded state (see e.g., Figure 6) or a fully expanded state (see e.g., Figure 7). Once catheter balloon 620 and mesh 630 are expanded to the appropriate position, the catheter balloon can be used to relieve the obstruction in a conventional angioplasty as described above in step 2080.

After the angioplasty procedure, a small volume of gas or liquid may be removed from catheter balloon 620 to partially deflate the catheter balloon in step 2090 (see e.g., Figure 8). During this time, the position of outer shaft 660 relative to inner shaft 610 is maintained so that mesh 630 is retained in a fully expanded condition, with the mesh in contact with the arterial wall. Mesh 630 is retained against the arterial wall even after catheter balloon 620 is deflated slightly and no longer bears against the mesh. This results in a small gap or plenum space P between balloon wall 622 and mesh 630. The partially deflated catheter balloon 620 still occupies a relatively large volume of space within the inter-occlusion balloon space S. The remaining space in inter-occlusion balloon space S that is not occupied by catheter balloon 620 is relatively small, forming a constricted area between balloon wall 622 and arterial wall V. This constricted area forms a narrow pathway between discharge port 668 and the area along the arterial wall being treated. The constricted area and narrow pathway limit the space through which the MNP 700 can travel, thereby guiding the MNP more efficiently toward the arterial wall.

To minimize risks associated with the stoppage of blood flow, the stoppage of blood flow in the artery is preferably limited to a very short period of time ti. Time t_x is preferably limited to two minutes. It is highly preferable to direct the MNP 700 toward the treatment area as quickly as possible during this brief period when blood flow is stopped. More rapid targeting of MNP 700 to the treatment area is achieved by partially deflating the catheter balloon 620, as previously described in step 2090, to form the constricted area and narrow pathway in the inter-occlusion balloon space S.

After two minutes, catheter balloon 620, first occlusion balloon 640 and second occlusion balloon 650 are all deflated and completely collapsed in step 2100 (see, e.g. Figure 9). This reestablishes blood flow through the treatment area. Mesh 630 remains fully expanded, and uniform magnetic field F is maintained to continue targeting the MNP 700 toward mesh 630 in contact with or adjacent to the arterial wall.

Uniform magnetic field F is removed after an optimal magnetic field exposure time t₂ in step 2110. The optimal magnetic field exposure time t₂ varies depending on many conditions and system parameters. Typically, an appropriate magnetic field exposure time t₂ is between about 25 minutes and about 30 minutes. Optimum magnetic field exposure times will vary however, and other ranges for t₂ may prove to be suitable or even optimal under certain conditions.

After uniform magnetic field F has been removed, mesh 630 is retracted to a fully collapsed condition around catheter balloon 620 in step 2120, as previously shown in Figure 2. At this stage, mesh 630 and all the balloons are collapsed, allowing magnetic targeting device 600 to be more easily removed from the treatment area in step 2130. Magnetic targeting device 600 can then be removed from the human or animal, or moved to another treatment area in the human or animal, where the foregoing method steps can be repeated.

As with Figure 14, the sequence of steps shown in Figure 15 represents only one possible sequence of steps. Other sequences of steps are possible and contemplated in accordance with the invention. Additional steps not specifically mentioned or shown in Figure 15 may also be performed.

While preferred embodiments of the invention have been shown and described herein, it will be understood that such embodiments are provided by way of example only. Numerous variations, changes and substitutions will occur to those skilled in the art without departing from the scope of the invention.

For example, the balloons described in accordance with the invention need not take the forms shown in the accompanying drawing figures, and may be formed in other shapes and configurations. Devices in accordance with the invention may include a plurality of catheter balloon sections, as opposed to a single catheter balloon. Each catheter balloon section may be configured in fluid communication with the same lumen in the catheter that inflates and deflates all of the balloon sections. Alternatively, each catheter balloon section may be arranged in fluid communication with its own lumen, i.e. a dedicated lumen for each balloon section. The dedicated lumens would allow individual balloon sections to be selectively inflated and deflated, independently of other balloon sections.

Accordingly, it is intended that the appended claims cover all such variations as fall within the scope of the invention.

Claims

CLAIMS What is Claimed :

1. A magnetic targeting device comprising :

a catheter portion;

a catheter balloon fluidly connected to the catheter portion ; and

a mesh surrounding the catheter balloon.

2. The magnetic targeting device of claim 1, wherein the catheter balloon is an angioplasty balloon.

3. The magnetic targeting device of claim 1, wherein the catheter balloon is a high pressure balloon formed of a non-compliant or low compliant material.

4. The magnetic targeting device of claim 1, wherein the mesh is formed of a magnetizable material.

5. The magnetic targeting device of claim 1, wherein the mesh is formed of 304 stainless steel wire, 430 stainless steel wire, or other stainless steels that are magnetizable.

6. The magnetic targeting device of claim 1, wherein the mesh is a braided mesh that defines a plurality of pores, each pore having a pore size.

7. The magnetic targeting device of claim 6, wherein the pore size of said pores is between about 250 microns and about 2000 microns.

8. The magnetic targeting device of claim 1, wherein the catheter balloon and the mesh are radially expandable from a radially retracted state to a radially expanded state.

9. The magnetic targeting device of claim 8, wherein the mesh radially expands to the expanded state in response to radial expansion of the catheter balloon inside the mesh.

10. The magnetic targeting device of claim 9 further comprising an outer shaft operably connected with the mesh, the outer shaft being axially displaceabie between a first axial position to radially expand the mesh and a second axial position to radially contract the mesh.

11. The magnetic targeting device of claim 1, wherein the catheter portion comprises a hollow inner shaft and a hollow outer shaft that surrounds and contains at least a portion of the hollow inner shaft.

12. The magnetic targeting device of claim 11, wherein the inner shaft defines a first lumen for containing a guidewire.

13. The magnetic targeting device of claim 12, wherein the inner shaft comprises a second lumen in fluid communication with the catheter balloon.

14. The magnetic targeting device of claim 13, further comprising a distal occlusion balloon coupled to the catheter portion.

15. The magnetic targeting device of claim 14, wherein the inner shaft comprises a third lumen in fluid communication with the distal occlusion balloon.

16. The magnetic targeting device of claim 15, wherein the inner shaft comprises a fourth lumen defining an accessory flush channel .

17. The magnetic targeting device of claim 13, further comprising a proximal occlusion balloon coupled to the catheter portion.

18. The magnetic targeting device of claim 17, wherein the outer shaft defines a primary lumen and a secondary lumen, at least a portion of the inner shaft being disposed in the primary lumen.

19. The magnetic targeting device of claim 18, wherein the inner shaft and outer shaft define an annular space between the inner shaft and outer shaft.

20. The magnetic targeting device of claim 19, wherein the outer shaft defines at least one port at a distal end of the outer shaft.

21. The magnetic targeting device of claim 20, wherein said at least one port is adjacent to the mesh.

22. The magnetic targeting device of claim 20, wherein said at least one port is axially positioned on the catheter portion between the distal occlusion balloon and the mesh.

23. The magnetic targeting device of claim 20, wherein said at least one port defines an injection port configured to release MNPs.

24. The magnetic targeting device of claim 1, wherein the mesh is radially expandable to a relatively expanded state, and the catheter balloon is expandable to an intermediate expanded state in the catheter balloon, the mesh and catheter balloon being separated by a narrow plenum space between the mesh and the catheter balloon.

25. A method of treating a medical condition in a human or animal with one or more therapeutic agents, the method comprising the steps of:

a) advancing a catheter to a treatment site in the human or animal, the catheter comprising a catheter balloon and a magnetizable mesh surrounding the catheter balloon; b) establishing a uniform magnetic field at the treatment site;

c) releasing a plurality of MNP containing the one or more therapeutic agents from the catheter to a location near the mesh in the uniform magnetic field, the MNPs comprising one or more magnetic field-responsive agents;

d) radially expanding the catheter balloon and the mesh until the mesh contacts the treatment area; and

e) maintaining the uniform magnetic field after the step of releasing the plurality of MNP to draw the MNP to the mesh and into contact with the treatment area.

26. The method of claim 25, wherein step a) comprises the step of advancing the catheter into an obstructed or partially obstructed area of an artery.

27. The method of claim 26, wherein step d) comprises the step of radially expanding the catheter balloon and mesh to open the obstructed or partially obstructed area of the artery in an angioplasty procedure.

28. The method of claim 25 comprising the step of radially retracting the catheter balloon after step d) to create a narrow plenum space between the catheter balloon and the wall of the artery.

29. The method of claim 28, wherein the step of radially retracting the catheter balloon comprises retracting the catheter balloon so that the catheter balloon is spaced from the wall of the artery by an average distance of about 1 millimeter.

30. The method of claim 25 further comprising the step of, before step c), inflating a first occlusion balloon located on the catheter to temporarily occlude the artery and limit blood flow past the treatment site.

31. The method of claim 30 further comprising the step of, before step c), inflating a second occlusion balloon located on the catheter to temporarily occlude the artery and limit blood flow past the treatment site, the first occlusion balloon and second occlusion balloon defining an inter-occlusion balloon space between the first and second occlusion balloons.

32. The method of claim 31 further comprising the step of deflating the second occlusion balloon approximately two minutes after the step of inflating the second occlusion balloon to at least partially restore blood flow in the artery.

33. The method of claim 30 further comprising the step of deflating the first occlusion balloon approximately two minutes after the step of inflating the first occlusion balloon to at least partially restore blood flow in the artery.

34. The method of claim 25, wherein step e) comprises the step of maintaining the uniform magnetic field for a total exposure time of t₂ minutes, wherein t₂ is between about 25 minutes and about 30 minutes.

35. The method of claim 25 further comprising the step of retracting the catheter balloon to a relatively retracted state after step e).

36. The method of claim 25 further comprising the step of retracting the mesh to a relatively retracted state after step e).

37. The method of claim 25 further comprising the step of removing the catheter from the human or animal after step e).

38. The method of claim 25 further comprising the step of moving the catheter to another treatment site in the human or animal after step e).

39. The method of claim 31 further comprising the step of aspirating the inter- occlusion balloon space before step c).

40. The method of claim 25, wherein the step of establishing a uniform magnetic field at the treatment site comprises establishing a uniform magnetic field of

0.1T.

41. The method of claim 25, wherein the step of radially expanding the catheter balloon and the mesh until the mesh contacts the treatment area comprises capturing the released MNP in the mesh as the mesh is expanded through the MNP to move the MNP toward the arterial wall .