Title:  System and methods for local delivery of an agent

United States Patent:  6,197,324

Assignee:  C. R. Bard, Inc. (Murray Hill, NJ)

Filed:  July 15, 1998

A system and method for implanting pellets containing local anesthetic agents into tissues of the heart for temporary treatment of angina pectoris. The mechanism of delivery can be transcatheter via chambers of the heart, endoscopic epicardial approach via minimally invasive transthoracic access, or intraoperative epicardial approach during open-chest surgery.

SUMMARY OF THE INVENTION

It is therefore, an object of the invention to provide methods of treatment of a coronary artery or cardiac indication that provide a longer duration of drug pendency at the site of a localized disease.

It is a further object of the invention to provide systems and methods that reduce or eliminate the downstream flow of a locally delivered agent.

Other objects of the invention will, in part, be obvious, and, in part, be shown from the following description of the systems and methods shown herein.

To these ends, the invention provides systems and methods for implanting a depot into a tissue wall to thereby deliver a therapeutic agent selected for the condition being treated. In one embodiment, the invention provides systems and methods for delivering a therapeutic agent into the myocardial tissue wall for treating various vascular conditions including restenosis, ischemic tissue, and myocardial infarction. Other applications of the systems and methods described herein include the delivery of angiogenesis compounds that can be implanted into ischemic tissue; and/or antiarrhythmic drugs that can be implanted at the sites of conduction abnormalities. Additionally, the systems and methods described herein can provide for local delivery of anesthetic agents to reduce the localized occurrence of pain and discomfort such as the pain and discomfort arising from angina pectoris. Accordingly, the agent being locally delivered can depend on the application at hand, and the term agent, or therapeutic agent, as employed herein will be understood to encompass any agent capable of being locally delivered including, but not limited to, pharmaceutical compositions or formulations, viral or non-viral vectors (e.g., adenovirus vectors, retroviral vectors and the like), implantable (genetically engineered) cells, plasmid-liposome complexes or other DNA delivery complexes, oligonucleotides or any other suitable composition compatible with the subject being treated.

In one embodiment the invention is understood as apparatus for delivering therapeutic agents, comprising an elongate flexible body having a proximal end and a distal end, a delivery chamber coupled to the distal end of the body and having a space for carrying the therapeutic agent, and a port for releasing the therapeutic agent therefrom. The apparatus further includes an actuator coupled to the distal delivery chamber and being capable of driving therapeutic agent through the port.

The terms proximal and distal as used herein will be understood to describe opposite ends of a device or element, and generally will be employed so that proximal is understood as "away from the heart" and distal is understood as "towards the heart" or to mean "toward the physician" and "away from the physician" respectively.

In one embodiment, the apparatus further includes a control mechanism that couples to the actuator and to the proximal end of the body for providing control of the actuator. In this way a user can operate the control mechanism for selectable delivery of the agent. Optionally, the apparatus can also include a "steering" mechanism for bending the distal end of the body to thereby allow the delivery chamber to be selectively aimed or directed within the chambers of the heart. The distal end of the flexible body can be dimensionally adapted to allow for transluminal delivery and for entry into the interior of a patient's heart. This allows the distal end of the apparatus, which carries the delivery chamber, to travel through the patient's vasculature, enter the patient's heart, and butt against or penetrate through the endocardial tissue and penetrate into the myocardium. To this end, the distal end of the delivery chamber can be further provided with a pointed distal end which is adapted to penetrate a tissue wall for delivering the therapeutic agent into the tissue wall.

In a further embodiment, the apparatus can further include a plunger for driving a therapeutic agent from the delivery chamber. The plunger can include a ratchet assembly for allowing the delivery of discrete volumes of therapeutic agent, or a discreet number of pellets containing a therapeutic agent. Alternatively, the plunger can be provided with a threaded assembly and worm gear assembly for rotatably advancing the plunger into the delivery chamber responsive to a rotating action. Accordingly, an actuator such as a plunger disposed within the delivery chamber can act on pellets of therapeutic agents stored within the delivery chamber to force the pellets from the delivery chamber and implant them within a tissue wall. Optionally a delivery chamber can be dimensioned to receive one or a plurality of pellets containing a therapeutic agent. The activation of the plunger or actuator can be by manipulation of a lever action handle mounted at the proximal end of the flexible body and coupled to the control mechanism. Alternatively, a rotary mechanism, optionally motorized, can be provided for rotating a threaded plunger to advance the plunger within the delivery chamber thereby forcing pellets of therapeutic agent from the chamber.

In a further embodiment of the invention, a mechanism is provided for receiving at least one pellet containing the therapeutic agent and having a pointed shape for facilitating implanting the pellet within a body of tissue. As discussed above, a plunger can be provided for forcing the pointed pellet from the delivery chamber and implanting the pellet within a tissue wall of the patient, such as within the myocardium.

In a further aspect, the invention can be understood as pellets adapted for carrying a therapeutic agent into the tissue wall of a patient. In one embodiment, the pellets include a radio-opaque marker typically located at the core of the pellet which facilitates the fluoroscopic viewing of the delivery of the pellets.

In yet a further aspect, the invention can be understood as methods for providing local delivery of a therapeutic agent which include the step of implanting the therapeutic agent into a portion of myocardial tissue. In one practice, the methods include the step of providing a catheter having a distal end adapted for delivering the therapeutic agent, guiding the catheter into the interior of a patient's heart and disposing the distal end of the catheter against an endocardial wall of the heart for implanting the therapeutic agent into the myocardial tissue. The step of providing a catheter can include the step of providing a steerable catheter which, optionally, can include a drilling element for penetrating a tissue wall such as the endocardium. In one practice, a plurality of pellets containing a therapeutic agent, or a plurality of therapeutic agents, are delivered sequentially into the myocardial tissue. Optionally, each pellet can contain a therapeutic agent and a radio-opaque marker.

In one practice of the invention, the local delivery of the therapeutic agent is accomplished by transluminal delivery in which the catheter is steered through access at the femoral artery or vein and directed into the heart. Optionally, a marker can be positioned in a selected portion of a coronary artery to identify a location for receiving the therapeutic agent. In this practice, the marker can be observed fluoroscopically during the procedure, and a treating physician can use the positioned marker for targeting the location of the myocardium into which the therapeutic agent is to be implanted.

In a further practice, the procedure includes a step of endoscopically delivering the therapeutic agent through the epicardium. In yet another practice, the therapeutic agent is implanted into the myocardial tissue during open chest surgery.

In a further aspect, the invention provides methods for delivering a therapeutic agent to a septal artery. In one practice, the method comprises the steps of providing a catheter having a distal end that is adapted for delivering the therapeutic agent, guiding the catheter into the interior of a patient's heart and disposing the distal end of the catheter against a septal wall of the heart for implanting the therapeutic agent into the septal tissue.

Claim 1 of 17 Claims

We claim:

1. A method for providing local delivery of a therapeutic agent, comprising the step of

implanting a therapeutically effective amount of a local anesthetic agent into a portion of myocardial tissue.

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