Cardiac drug delivery system

• US 6,086,582 A
• Filed: 03/13/1997
• Issued: 07/11/2000
• Est. Priority Date: 03/13/1997
• Status: Expired due to Term

• Current Assignee: BioCardia, Inc
• Original Assignee: John D. Altman, Peter A. Altman
• Inventors: Altman, John D., Altman, Peter A.
• Primary Examiner(s): Lateef, Marvin M.
• Assistant Examiner(s): MANTIS MERCADER, ELENI M
• Application Number:
  US08/816,850
• Time in Patent Office: 1,216 Days
• Field of Search: 600/374, 600/508, 606/47, 606/41, 606/45, 606/48, 606/44, 607/3, 607/120-122, 607/126-128, 607/60-61, 607/32-33
• US Class Current: 606/41
• CPC Class Codes: A61B 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 2017/00247 Making holes in the wall of the heart, e.g. laser Myocardial revascularization
• CPC Class Codes: A61B 2018/00011 with fluids
• CPC Class Codes: A61B 2018/00273 Anchoring means for temporary attachment of a device to tissue
• CPC Class Codes: A61B 2018/00351 Heart
• CPC Class Codes: A61B 2018/00392 Transmyocardial revascularisation
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00839 Bioelectrical parameters, e.g. ECG, EEG
• CPC Class Codes: A61B 2018/1425 Needle
• CPC Class Codes: A61B 2018/1435 Spiral
• CPC Class Codes: A61B 2218/002 Irrigation
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61M 2025/0089 Single injection needle protruding axially, i.e. along the longitudinal axis of the catheter, from the distal tip
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: A61N 1/0575 with drug delivery
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

A system is disclosed, for administering a therapeutic agent locally and to a depth within cardiac tissue. An elongate, flexible catheter contains a flexible electric conductor and supports at its distal end an implantable electrode incorporating a penetrating element, typically a fixation helix or a linear needle that penetrates cardiac tissue as the electrode is implanted. A therapeutic agent is delivered through the electrode, to the cardiac tissue surrounding the penetrating element. The electrode acts as a sensor, electrically coupled through the flexible conductor, and monitors an electrical condition of the surrounding cardiac tissue. A controller is coupled to the sensor and to a pump or reservoir containing the therapeutic agent, to control delivery of the agent responsive to the sensed electrical condition. The implanted electrode further can be used to deliver RF current to ablate the surrounding tissue. Several embodiments feature a distal reservoir adjacent the electrode, for effecting transient deliveries of the therapeutic agent in minute quantities or chronic delivery of growth factors. Another embodiment incorporates a bilumen catheter and a set of unidirectional valves, to facilitate changing therapeutic agents or purging the catheter of an agent after delivery.

Claims

1. A system for supplying a therapeutic agent locally to a depth within cardiac tissue, including:

an elongate, flexible, dielectric and biocompatible catheter body;

an elongate and flexible electric conductor coextensive with the catheter body;

a conductive implantable electrode including a distally located penetrating element adapted to penetrate cardiac tissue to a depth within surrounding cardiac tissue;

a conductive coupling structure electrically coupling a proximal portion of the electrode with respect to a distal end of the flexible electric conductor;

a fluid passage through the electrode, open to an exterior of the electrode at said proximal portion and at said penetrating element;

a source of a therapeutic agent, fluid coupled to the fluid passage at said proximal portion to deliver a therapeutic agent to said surrounding cardiac tissue via the fluid passage;

a sensor electrically coupled with respect to a proximal end of the flexible electric conductor for monitoring an electrical condition of said surrounding cardiac tissue; and

a controller operatively coupled to the sensor and to the source, adapted to control the delivery of the therapeutic agent responsive to the sensed electrical condition, thereby to effect a transient delivery of the therapeutic agent, on demand, and with the therapeutic effect substantially confined to cardiac tissue.

2. The system of claim 1 wherein:

said penetrating element comprises a helical coil, which tends to fix the electrode within the cardiac tissue as it penetrates the tissue.

3. The system of claim 1 wherein:

said fluid passage is open to the electrode exterior at the penetrating element through a distal end aperture at a distal tip of the penetrating element.

4. The system of claim 3 wherein:

said fluid passage further is open at the penetrating element through a plurality of apertures disposed along the penetrating element.

5. The system of claim 1 wherein:

said source comprises a reservoir containing the therapeutic agent and a delivery means for effecting delivery of the agent from the reservoir to the fluid passage.

6. The system of claim 5 wherein:

said reservoir is disposed near a proximal end of the catheter body, and said source further includes a flexible tubing extending from the proximal end of the catheter body to the distal end thereof, and having an internal lumen fluid-coupled to the fluid passage.

7. The system of claim 6 wherein:

said reservoir is adapted for subcutaneous implantation.

8. The system of claim 1 wherein:

said electrical condition comprises an electrical conduction or a time-dependent voltage.

9. The system of claim 1 wherein:

said flexible electrical conductor is disposed within the catheter body.

10. The system of claim 9 wherein:

said flexible electric conductor is one of;

a helically wound coil and a cable.

11. The system of claim 1 further including:

a surface electrode positionable proximate and in spaced apart relation to said implantable electrode, an electrically conductive path coupling the surface electrode to the controller, and a means acting through the flexible electric conductor to bias the implantable electrode with respect to the surface electrode to generate RF current between the implantable and surface electrodes.

12. A process for treating an arrhythmogenic site in cardiac tissue, including:

locating an arrhythmogenic site;

using a catheter to intraluminally deliver an electrode to the arrhythmogenic site, and to implant the electrode at the site, causing a portion of the electrode to penetrate cardiac tissue at the site;

after implantation, delivering a therapeutic agent to the cardiac tissue at the site;

sensing an electrical condition of the cardiac tissue proximate the site after said delivery of the therapeutic agent has begun, to evaluate whether said delivery of the therapeutic agent has had a desired effect; and

performing alternatively, one of the following steps;

(i) using the electrode to deliver RF energy to said cardiac tissue at the site to ablatively destroy the tissue;

and

(ii) using the catheter to remove and reposition said electrode responsive to determining that administration of the therapeutic agent has not had the desired effect.

13. A process for effecting a controlled, transient delivery of a therapeutic agent to cardiac tissue, including:

using an elongate and flexible catheter that supports at its distal end an electrode that includes a distal penetrating element, to intraluminally deliver the electrode to a selected cardiac tissue site and to implant the electrode at said site to insert the penetrating element to a depth within the cardiac tissue, whereby the penetrating element is surrounded by the cardiac tissue;

after the electrode is implanted, sensing electrical impulses conducted through the penetrating element and an elongate conductor coextensive with the catheter and electrically coupled to the penetrating element, thus to monitor an electrical condition of the surrounding tissue for an arrhythmic event;

responsive to sensing an arrhythmic event, delivering a therapeutic agent through said electrode and to the surrounding cardiac tissue through an opening in the penetrating element, thus to effect a delivery to a depth within the surrounding cardiac tissue;

after said delivery, further monitoring the electrical condition of the surrounding tissue to determine whether the delivery has terminated the arrhythmia.

14. The process of claim 13 wherein:

said delivery includes delivering the therapeutic agent from a pump at a proximal end of the catheter through a fluid conduit within the catheter fluid coupled at its distal end to a fluid passage through said electrode.

15. The process of claim 13 wherein:

said delivery comprises applying pressure to a reservoir of the therapeutic agent disposed within a housing at a distal end of the catheter, to force the therapeutic agent out of the reservoir and into the adjacent cardiac tissue through a fluid passage formed in the electrode.

16. A device for treating cardiac tissue locally to a depth within the cardiac tissue, including:

an elongate, flexible, dielectric and biocompatible catheter body;

an electrically conductive implantable first electrode supported at a distal end of the catheter body and including a distally located penetrating element adapted to penetrate cardiac tissue to a depth within surrounding cardiac tissue;

an elongate and flexible electric conductor extending along the catheter body and electrically coupled to the implantable first electrode at a proximal portion thereof;

a fluid passage through the electrode, open to an exterior of the electrode at said proximal portion and at said penetrating element;

a therapeutic agent source, fluid coupled to the fluid passage at the proximal portion, for delivering therapeutic agents to the surrounding cardiac tissue via the fluid passage; and

a second electrode positionable in proximate, spaced apart relation to said first electrode, and a voltage biasing means adapted to bias the first electrode and the second electrode with respect to one another to generate RF current between the first and second electrodes.

17. The device of claim 16 wherein:

said second electrode is a surface electrode, and the biasing means acts through the flexible electric conductor.

18. The device of claim 16 further including:

a sensor electrically coupled with respect to a proximal end of the flexible electric conductor for monitoring an electrical condition of said surrounding cardiac tissue.

19. A transmiocardial revascularization device, including:

an elongate, flexible, dielectric and biocompatible catheter body;

an implantable component supported at a distal end of the catheter body and including a distally located penetrating element adapted to penetrate cardiac tissue to a depth within surrounding cardiac tissue;

a means for providing tissue altering energy to form channels within said surrounding cardiac tissue;

a fluid passage through the implantable component open to an exterior of the implantable component at a proximal end portion thereof and at said penetrating element;

a therapeutic agent source, fluid coupled to the fluid passage at said proximal portion, for delivering therapeutic agents to the surrounding cardiac tissue via the fluid passage.

20. The device of claim 19 wherein:

said implantable component is electrically conductive, and said means for providing tissue altering energy comprises a surface electrode positionable in proximate, spaced apart relation to the implantable component, and a means for biasing the surface electrode and implantable component relative to one another, to generate RF current between the implantable component and the surface electrode.