WO2011150200A2

WO2011150200A2 - Non occluding firing catheter for prolonged drug delivery

Info

Publication number: WO2011150200A2
Application number: PCT/US2011/038128
Authority: WO
Inventors: Angelo Skulas; Camillo Ricordi
Original assignee: University Of Miami
Priority date: 2010-05-26
Filing date: 2011-05-26
Publication date: 2011-12-01
Also published as: WO2011150200A3

Abstract

A medical device for transmitting an electric pulse to vascular tissue proximate an implantable catheter to prevent vascular occlusion. The medical device includes an elongate body defining a proximal and distal end. The elongate body further defines an injection lumen and a wire lumen, the injection lumen being in fluid communication with a fluid source. A wire is at least partially disposed within the elongate body, and has a proximal end and a distal end. The distal end of the wire is at least partially disposed within the wire lumen, and the proximal end of the wire is connected a pulse generator, wherein the pulse generator transmits an electric pulse along the wire toward the distal end of the elongate body.

Description

NON OCCLUDING FIRING CATHETER FOR PROLONGED DRUG

DELIVERY

FIELD OF THE INVENTION

The present invention relates to a medical device, and more particularly to a catheter for a drug delivery device.

BACKGROUND OF THE INVENTION

Vascular disease is often caused by the formation of lesions or plaque within the arterial walls or the coronary vasculature. A variety of different minimally invasive procedures have been developed for treating diseases associated with the presence of vascular lesions or plaque. Such treatment methodologies often involve the use of catheters to mechanically, pharmacologically, or cryogenically reduce or remove the plaque or lesion. These catheters often include a drug eluding treatment tip or stent positionable within a vessel, proximal the plaque or lesion, to treat the diseased area. However, the foreign material of the stent or catheter may cause inflammation and induce tissue proliferation around the treatment site resulting in restinosis. If restinosis occurs, the vasculature may become occluded and cause ischemia that may result in infarction.

Similarly, drug-eluding catheters positionable within a vessel for an extended period of time, such as an insulin delivery system, may cause an inflammatory response within the vasculature, which may damage or destroy tissue around the catheter. The risks associated with these long term catheterization procedures include bleeding, allergic reactions, and infarction. Moreover, patients with diabetes, or conditions that require long term implantation of in vivo drug eluding materials, may require intravenous immunosuppressive antiproliferative drugs to avoid rejecting the catheter or implant. These immunosuppressive drugs, however, may cause complications as a side effect of suppressing the immune system.

An alternative approach to inhibit restinosis and vasculature occlusion has been to coat the catheter or stent with a low dose of immunosuppresive

antiproliferative drug. However, this procedure may put patients at risk for stent thrombosis, or the formation of a clot in the stent. The risk of thrombosis is present because the immunosuppresive antiproliferative drugs, while reducing inflammation, inhibit the proliferation of macrophages, which would accumulate around the foreign body stent and nearby vasculature. The inhibition of macrophages may limit re- endothelialization or tissue healing. The lack of healing, in turn, may result in the stent being an exposed surface on which a life-threatening clot can form.

Another method for preventing vascular occlusion has been to monitor or sense electrocardiogram (ECG) readings to diagnosis a sudden onset of ischemia. In response to a sudden change in ECG readings, an implantable pulse generator may trigger a delivery device to stimulate the endothelial cells, and to release one or more cellular products to dissolve the clot and prevent infarction from occurring. However, these devices may be either over or under sensitive to ischemic conditions, and as a result, may trigger unnecessary delivery of cellular products, or alternatively fail to prevent arterial occlusion.

Yet another method for preventing vascular occlusion is to measure an electrical current provided to an infusion pump compared to a baseline current. If the current spikes, an alarm is triggered and the infusion pump is stopped or slowed.

However, current measurements within the vasculature may be variable in response to variety of stimuli. As with the ECG measurement devices, these devices may be over or under sensitive and are dependent upon a predetermined threshold, which may be variable and therefore unreliable from patient to patient.

It is therefore desirable to provide a safe and reliable medical device and method for preventing all forms of vascular occlusion in response to implantable or removably insertable catheter systems, including drug delivery systems. Also desirable is a device that conveys the benefits of an implantable pulse generator, which stimulates the endothelial cells to dissolve a blood clot and prevent infarction and occlusion, but yet is not dependent on ECG (or similar) measurement devices.

SUMMARY OF THE INVENTION

This present invention advantageously provides for a medical device and method for transmitting an electric pulse to vascular tissue proximate a removably insertable or implantable catheter to prevent all forms of vascular occlusion and other problems associated with the use of implantable catheters or stents. Through laboratory experiments, it has been discovered that the application of an electrical potential difference will prevent cells (including myofibroblasts, which are the first cells that get activated after injury and inflammation) from either adhering to or migrating toward the electrode. Similarly, the device described herein transmits an electric pulse to vascular tissue that will prevent the buildup of cell matter and plaque in the vasculature proximate a removably insertable or implantable catheter.

Furthermore, this device is particularly well suited for use with insulin pumps and chronic drug delivery systems, including local immunosuppression /

immunomodulation in cells and tissues containing hybrid devices.

The medical device includes a catheter defining a lumen. A wire is disposed within the catheter lumen. The wire is further coupled to a pulse generator, wherein the pulse generator transmits an electric pulse to the wire.

In one embodiment of the present invention, the medical device includes a catheter defining an elongate catheter body, a proximal end, and a distal end. The catheter further defines a fluid injection lumen and a wire lumen, the injection lumen being in fluid communication with a fluid source. A first portion of a wire is disposed within the wire lumen and a second portion of the wire is connected to a pulse generator, wherein the pulse generator transmits an electric pulse along the wire toward the distal end of the catheter.

In another embodiment of the present invention, the method includes providing a catheter defining an elongate catheter body, a proximal end, and a distal end. The catheter further defines a lumen and has a wire disposed within lumen. The catheter is positioned within a blood vessel proximate a wall of the blood vessel. An electric pulse is transmitted along the wire, the electric pulse being further transmitted to the distal end of the catheter.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention, and the attendant advantages and features thereof, will be more readily understood by reference to the following detailed description when considered in conjunction with the accompanying drawings wherein:

FIG. 1 is an embodiment of the catheter in accordance with the principals of the present invention; FIG. 2 is a close-up view of the distal end of the catheter of FIG. 1;

FIG. 3 is the catheter of FIG. 1 with a multi-chambered pulse generator and a plurality of wires;

FIG. 4 is the catheter of FIG. 1 with a treatment delivery device at the proximal end;

FIG. 5 is the catheter of FIG. 1 with a treatment delivery device at the distal and proximal ends;

FIG. 6 is the catheter of FIG. 1 with a treatment delivery device at the distal and proximal ends; and

FIG. 7 is a close-up view of the catheter of FIG. 6.

DETAILED DESCRIPTION OF THE INVENTION

This present invention advantageously provides for a medical device and method for transmitting an electric pulse to vascular tissue proximate a removably insertable or implantable catheter to prevent vascular occlusion.

As seen in FIGs. 1 and 2, the medical device 10 may include a catheter 12 including an elongate body 14 passable through a patient's vasculature and/or proximate to a tissue region for treatment. The elongate body 14 may define a proximal end 16, and a distal end 18, and may further include one or more lumens disposed within the elongate body 14, which may provide mechanical, fluid, and/or electrical communication between the proximal 16 and distal 18 ends of the elongate body 14. The distal end 18 of the elongate body 14 may be coupled to a specialized catheter tip (as seen in FIGs. 5-7) that suits the needs of the particular procedure for which the device is used, such as a drug delivery device. Likewise, the proximal end 16 of the elongate body 14 may include a connector 19 that is matable to a device such as an insulin pump or other fluid reservoir. The elongate body 14 may further be composed of materials, such as a wire braid, that make the elongate body 14 torqueable in response to an applied force for overall catheter steering within the vasculature.

The device 10 may further be implantable or removably insertable within the vasculature of the patient, and may be located entirely or at least partially within the body of the patient. For example, the elongate body 14 may be removably inserted within the vasculature for short term procedures such as stent implantation, or the entire device 10 may be implanted within the patient' s body for long-term drug delivery. As shown, for example, in FIGs. 5-7, the distal end 18 of the elongate body 14 may be connected to one or more specialized medical device catheter tips (e.g. , drug eluding device). Additionally or alternatively, the distal end 18 of the elongate body 14 may include a conductive material to transmit heat or electric energy for ablation procedures (not shown in the figures).

The medical device 10 may include a handle (not shown in the figures) coupled to the proximal end 16 of the elongate body 14. The handle may include (house) circuitry or other electronics used for controlling the medical device 10 or other component of the system (such as one or more pressure sensors to monitor fluid pressure within the device 10). Additionally, a pulse generator 25 may be located within the handle. The handle may further include connectors that are matable to a fluid supply, exhaust system, and/or control unit either directly or with one or more umbilicals, and/or the handle may include a pressure relief valve in fluid

communication with the fluid injection lumen and/or exhaust lumen to automatically open under a predetermined threshold value in the event that value is exceeded.

Although various configurations of the device 10 are shown in FIGs. 1-7 without a handle, it will be appreciated by those of ordinary skill in the art that a typical catheter handle known in the art could be included in the device 10. Moreover, the device is suitable for use in any catheter configuration.

The device is suitable for use in all types of catheter configurations and therefore may include may include a fluid supply (such as a coolant) used for thermal ablation procedures, as well as various control mechanisms for the device. A control unit may also be present, which may include pumps, valves, controllers or the like to recover and/or re-circulate fluid delivered to the handle, the elongate body 14, and/or the fluid pathways of the medical device 10 (not shown in the figures).

A vacuum pump in the control unit may create a low-pressure environment in one or more conduits within the device 10 so that fluid is drawn into the lumen(s) of the catheter 12, away from the distal portion and towards the proximal portion of the catheter 12. The control unit may include one or more controllers, processors, and/or software modules containing instructions or algorithms to provide for the automated operation and performance of the features, sequences, or procedures described herein. Although the device 10 is shown in FIGs. 1-7 without a fluid supply, control console, or vacuum pump, it will be appreciated by those of ordinary skill in the art that these components can be included in the device 10.

A conductive material, such as a metal wire 27, may be entirely or partially disposed within the elongate body 14, and inserted into the wire lumen 30 of the elongate body 14 through a wire port 29. The wire 27 may be a single straight segment of conductive material, or it may be a braid, twist, or mesh of several segments of conductive material (as the wire 27 shown exiting the pulse generator 25 in, for example, in FIG. 1). The wire 27 may define a proximal end 32 and a distal end 34, wherein the proximal end 32 of the wire 27 may be operably connected to a pulse generator 25, such as a pacemaker, and the distal end 34 of the wire 27 may be disposed within the distal end 18 of the elongate body 14. The distal end 34 of the wire 27 and the distal end 18 of the elongate body 14 may be substantially

coterminous or the distal end 34 of the wire 27 may protrude from the distal end 18 of the elongate body 14. In one embodiment, the wire may be composed of titanium, titanium alloy, or other metal having similar properties within the human body.

Titanium is a desirable material because of its strength, chemical stability, corrosion resistance, and because it remains in a passive state after implantation.

The pulse generator 25 is a small device resembling a pacemaker in size and function, preferably not exceeding 50 mm in length. The pulse generator 25 may be located within the catheter handle or may exist separately from the catheter handle, connected only by the wire 27 that is inserted into the wire lumen 30 (for example when the device 10 does not include a handle). Additionally, the pulse generator 25 may contain an internal power source such as a battery (not shown in the figures) to supply the electrical energy or may be connected to an external power source (not shown in the figures). The pulse generator 25 may also include a transducer or other circuitry (not shown in the figures) to transform a generated electrical current into one or more electric pulses to be transmitted along the wire 27 toward the distal end 36 of the catheter 12. The pulse generator 25 may be single chambered 38 or multi chambered 39 (reference number 39 representing a plurality of chambers), such that additional wires may be in electrical communication with a respective the multiple chambers. For example, a plurality of wires 40 may be disposed within the elongate body 14, wherein each wire is in electrical communication with a chamber 39 within the pulse generator, as seen in FIG. 3. Each chamber 39 may be programmed to generate and fire electrical pulses at fixed or variable frequencies. In such an embodiment, a first wire may fire low frequency pulses, for example 1-30 beats per minute (BPM) and a second wire may fire high frequency pulses, for example 30-100 BPM. The number and duration of the pulses may also be fixed or variable depending on the desired treatment. The wire may transmit the pulses to the distal end 36 of the elongate body 14, or may alternatively transmit the electric pulses directly to the treatment site.

Referring now to FIG. 4, the device 10 of the present invention may define a wire lumen 30 and wire lumen port 29 for insertion of the wire 27 into the elongate body 14. The catheter 12 may further define a fluid injection lumen 43 in fluid communication with one or more fluid reservoirs 42, such as an insulin pump. The fluid reservoir 42 may be in fluid communication with the distal end 36 of the catheter 12, and may be connected to the proximal end 16 of the elongate body 14 by a connector 19 or one or more umbilicals (not shown in the figures). For example, the fluid injection lumen 43 may deliver one or more fluids such as pharmacological agents, insulin, or coolant from the reservoir 42, such as an insulin pump, to a treatment site proximate the distal end 36 of the catheter 12. The reservoir 42 may include one or more displays, controls, or the like.

The device 10 may include one or more sensors 44 to monitor the operating parameters throughout the system, including for example, pressure, temperature, flow rates, volume, or the like in the control unit and/or the medical device 10, in addition to monitoring, recording or otherwise conveying measurements or conditions within the medical device 10 or the ambient environment at the distal portion of the medical device 10. The one or more sensors 44 may be in electrical communication with a dialysis pump, control unit, insulin pump, or the like for initiating or triggering one or more alerts or therapeutic delivery modifications during operation of the medical device 10. One or more valves, controllers, or the like may be in communication with the sensor(s) to provide for the controlled dispersion or circulation of fluid through the lumens/fluid paths of the medical device 10. Such valves, controllers, or the like may be located in a portion of the medical device 10 and/or in a control unit.

The device 10 may include one or more glucose measurement sensors 44 operably connected to an insulin pump 42. As an example, the catheter 12 may be implanted in a patient's peritoneal cavity, from which the glucose measurement sensors 44 may perceive reduced levels of plasma glucose. When lowered glucose levels are detected, the sensors 44 function to operably engage insulin pump 42 on to deliver insulin to the patient.

The device 10 may also function as a dialysis device. The process of dialysis involves the use of a peritoneal dialysate that creates an osmotic gradient (i.e. the peritoneal dialysate is hyperosmolar relative to plasma) that causes the influx of water into the peritoneal cavity. Glucose is commonly used as the osmotic agent. In one embodiment of the device 10, one or more glucose measurement sensors 44 operably connected to a pump may be located in the fluid reservoir, the fluid injection lumen, the catheter handle, or any other appropriate sensor location. As water moves into the peritoneal cavity and the osmolality of the dialysate is reduced, the sensor 44 perceives reduced glucose and functions to operably engage the pump, thereby removing the peritoneal dialysate and waste fluids from the patient.

Referring now to FIG. 5, the proximal end 16 of the elongate body 14 is connected to an insulin pump 42 by a connector 19. The insulin may flow from the insulin pump 42 through an injection lumen 43 toward the distal end 36 of the catheter 12 to a treatment delivery device 45 coupled to the distal end 18 of the elongate body 14. The treatment delivery device 45 may be an insulin delivery device 47, defining a porosity through which the insulin may pass into the patient's body. A pulse generator 25, such as a pacemaker, may be included having a wire 27 with a proximal end 32 and distal end 34. The wire 27 may be in electrical communication with the pulse generator 25, the proximal end 32 of the wire 27 extending from a portion of the pulse generator 25. The distal end 34 of the wire 27 may further be at least partially disposed within a wire lumen 30. The wire 27 may further be inserted through the wire lumen port 29 into an electrically insulated wire lumen 30, such that the electrically charged wire 27 may be isolated from a fluid flowing within the injection lumen 43. In operation, for example, the insulin may flow from the insulin pump 42 through the injection lumen 43 toward the distal end 32 of the catheter 12. Additionally, an electric pulse may be transmitted from the pulse generator 25 along the wire 27 disposed within the wire lumen 30. Fluid may egress from the distal end 36 of the catheter 12 toward a target treatment location. Concomitantly or

consecutively, one or more electric pulses may be transmitted along the wire 27 toward the distal end 36 of the catheter 12. The electric pluses may further be transmitted to the vascular tissue proximate the treatment location, which may prevent vascular occlusion after removable insertion or long term implantation of the catheter 12. Alternatively or additionally, the electric pulses may produce micrometric movement of the wire 27, resulting in movement of the distal end 36 of the catheter 12, which may also prevent vascular occlusion.

Now referring to FIGS. 6-7, the distal end 18 of the elongate body 14 may be coupled to a treatment delivery device 45. The treatment delivery device 45 may be, for example, a thermal energy transmission device (such as a metallic tip or balloon) for use in procedures that require vascular tissue ablation. Alternatively, the treatment delivery device 45 may be a device for delivering drugs to a treatment site, a stent, or it may be a hybrid device containing cells. The treatment delivery device 45 may be cylindrical, round, flat, or helical in shape and may be porous to provide for drug delivery distribution at the distal end 18 of the elongate body 14. FIGs. 6 and 7 show a treatment delivery device 45 that includes a thermally conductive tip with an expandable mesh 48. FIG. 7 is a close-up view of the device of FIG. 6.

It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described herein above. In addition, unless mention was made above to the contrary, it should be noted that all of the accompanying drawings are not to scale. A variety of modifications and variations are possible in light of the above teachings without departing from the scope and spirit of the invention, which is limited only by the following claims.

Claims

What is claimed is:

1. A medical device for transmitting an electric pulse to vascular tissue, comprising:

an elongate body defining a lumen;

a wire disposed within the lumen, the wire being coupled to a pulse generator, wherein the pulse generator transmits an electric pulse to the wire.

2. The medical device of claim 1, wherein the device further comprises a drug delivery device coupled to the distal end of the elongate body.

3. The medical device of claim 1, wherein the distal end of the elongate body includes a thermally conductive tip.

4. The medical device of claim 1, wherein the elongate body is at least partially composed of a torqueable material.

5. A catheter for transmitting an electric pulse to vascular tissue, comprising: an elongate body defining a proximal end and a distal end, the elongate body further defining a wire lumen and an injection lumen, the injection lumen being in fluid communication with a fluid reservoir;

a wire defining a proximal end and a distal end, wherein the distal end of the wire is disposed within the wire lumen and the proximal end of the wire is operably connected to a pulse generator; and wherein the pulse generator transmits an electric pulse along the wire toward the distal end of the catheter.

6. The medical device of claim 5, wherein the pulse generator includes an internal power source.

7. The medical device of claim 5, wherein the pulse generator is operably connected to an external power source.

8. The medical device of claim 5, wherein the pulse generator includes a transducer.

9. The medical device of claim 5, wherein the pulse generator includes a chamber in communication with the wire.

10. The medical device of claim 5, wherein the pulse generator includes a plurality of chambers, each chamber being in connection with a single wire, and each chamber being independently programmable to generate and fire electrical pulses at fixed or variable frequencies.

11. The medical device of claim 10, wherein at least one wire generates and fires low frequency electrical pulses of no more than 30 beats per minute.

12. The medical device of claim 5, wherein the device includes one or more glucose sensors in electrical communication with the fluid reservoir.

13. The medical device of claim 11, wherein the wire is at least partially composed of titanium.

14. The medical device of claim 5, wherein the pulse generator micrometrically moves the wire and the distal end of the elongate body.

15. The medical device of claim 5, wherein the distal end of the elongate body is coupled to a thermal energy transmission device operable to supply ablative energy.

16. The medical device of claim 5, wherein the distal end of the elongate body is coupled to a drug delivery device.

17. The medical device of claim 15, wherein the drug delivery device is porous.

18. A method for transmitting an electric pulse to vascular tissue, comprising: providing a medical device having an elongate body defining a proximal end and a distal end, the elongate body further defining a wire lumen and having a wire disposed within the lumen; positioning the elongate body of the device within a blood vessel proximate a wall of the blood vessel; and

transmitting an electric pulse along the wire toward the distal end of the elongate body.

19. The method of claim 17, wherein the medical device further defines a fluid injection lumen operably connected to a fluid reservoir.

20. The method of claim 18, wherein the wire defines a proximal end and a distal end, and wherein the proximal end of the wire is operably connected to an electric pulse generator including a single chamber and an internal power source.