Drug delivery catheter with internal ultrasound receiver

• US 20020068869A1
• Filed: 06/26/2001
• Published: 06/06/2002
• Est. Priority Date: 06/27/2000
• Status: Abandoned Application

• Current Assignee: PharmaSonics, Inc.
• Original Assignee: PharmaSonics, Inc.
• Inventors: Cowen, Mark, Zuk, Robert, Corl, Paul D., McKenzie, John, Brisken, Axel
• Application Number:
  US09/893,341
• Publication Number:
  US 20020068869A1
• Time in Patent Office: Days
• US Class Current: 600/439
• CPC Class Codes: A61B 2017/22001 Angioplasty, e.g. PCTA
• CPC Class Codes: A61B 2017/22051 with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation A61B2017/22048, A61B2017/3486 take precedence
• CPC Class Codes: A61B 2090/3786 receiver only
• CPC Class Codes: A61N 2007/0065 Concave transducers
• CPC Class Codes: A61N 2007/0078 with multiple treatment transducers
• CPC Class Codes: A61N 2007/0095 by modifying an excitation signal
• CPC Class Codes: A61N 2007/027 with multiple foci created simultaneously
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092

Abstract

Transducers and systems for applying ultrasonic energy to enhance drug delivery are illustrated.

Claims

1. A combined system for drug delivery and therapeutic ultrasound deliver, comprising:

a catheter having an ultrasound receiver positioned at its distal end.

2. The system of claim 1, further comprising:

an external ultrasound delivery system.

3. The system of claim 2, wherein the ultrasound receiver positioned at the distal end of the catheter assists an operator in directing a beam emitted by the external ultrasound delivery system towards the ultrasound receiver, and thereby, towards the distal end of the catheter.

4. The system of claim 2, wherein,

the external ultrasound delivery system delivers ultrasound of a type to enhance drug delivery uptake.

5. The system of claim 2, wherein,

the external ultrasound delivery system delivers ultrasound of a type to enhance gene delivery transfection.

6. The system of claim 2, wherein,

the external ultrasound delivery system delivers ultrasound of a type to inhibit intimal hyperplasia.

7. The system of claim 2, wherein,

the external ultrasonic ultrasound delivery system delivers ultrasound of a type to enhance a healing response.

8. The system of claim 1, wherein the ultrasound receiver comprises:

a piezoelectric ceramic hydrophone.

9. The system of claim 1, wherein the ultrasound receiver is cylindrical shaped.

10. The system of claim 1, wherein the ultrasound receiver is about 0.07 inches thick, 0.030 inches in outer diameter and about 0.020 inches long.

11. The system of claim 1, further comprising:

a balloon disposed on the distal end of the catheter.

12. The system of claim 2, wherein the external ultrasound delivery system comprises:

a single ultrasound transducer element.

13. The system of claim 2, wherein the external ultrasound delivery system comprises a wide-aperture delivery system which comprises:

a housing;

a large surface area transducer disposed internally at one end of the housing;

a window disposed at an opposite end of the housing; and

a water path between the transducer and the window.

14. The system of claim 13, wherein the transducer is a single circular element.

15. The system of claim 13, wherein the transducer comprises an array of annular elements, one with in another.

16. The system of claim 2, wherein the external ultrasound delivery system comprises:

an array of phased transducers.

17. The system of claim 16, wherein the array of phased transducers is curved, thereby directing ultrasound emissions to a target region of tissue.

18. The system of claim 16, wherein the array of phased transducers is flat, whereby the electronic timing of ultrasonic emission directs the ultrasound beam to a target region in the tissue.

19. The system of claim 17, wherein the array of phased transducers is shaped as an elongated rectangle such that ultrasound emissions are directed to an elongated target region of tissue.

20. The system of claim 16, wherein successive rows of transducers in the array of phased transducers are staggered with respect to one another, such that ultrasound energy is directed to a target region of tissue from several planes.

21. The system of claim 2, wherein the external ultrasound delivery system emits ultrasound with a center frequency of 0.2 to 5.0, and more preferably 0.3 to 3.0, and most preferably about 0.947 MHz.

22. The system of claim 2, wherein the external ultrasound delivery system emits ultrasound with an amplitude of 0.2 to 10.0, and more preferably 0.5 to 5.0, and most preferably about 1.8 MI.

23. The system of claim 2, wherein the external ultrasound delivery system emits ultrasound with a burst mode cycle of 1 to 1000, and more preferably 2 to 5000, and most preferably about 30.

24. The system of claim 2, wherein the external ultrasound delivery system emits ultrasound with a burst mode repetition of 0.1 to 50, and more preferably 1 to 20, and most preferably about 1.893 kHz.

25. The system of claim 2, wherein the external ultrasound delivery system emits ultrasound with a duty cycle of 0.1 to 50, and more preferably 1 to 20, and most preferably about 6.0%.

26. The system of claim 2, wherein the external ultrasound delivery system emits ultrasound with an exposure time of 10 to 1800, and more preferably 30 to 900, and most preferably about 60.0 seconds.

27. The system of claim 2, wherein the external ultrasound delivery system emits ultrasound with a beam width at −

6 dB of 2 to 50, and more preferably 5 to 25, and most preferably about 10.0 mm.

28. A method for enhancing drug delivery comprising:

delivering a drug into a target region of tissue with a catheter;

emitting therapeutic ultrasound from an external emitter in a direction generally towards the target region of tissue, the therapeutic ultrasound enhancing drug delivery;

monitoring a signal from an ultrasound receiver positioned on the distal end of the catheter; and

adjusting the direction of the therapeutic ultrasound emitted from the external emitter in response to the strength of the signal from the ultrasound receiver such that the therapeutic ultrasound emitted by the external emitter targets the target region of tissue.

29. A method for enhancing gene transfection, comprising:

delivering a gene into a target region of tissue with a catheter;

emitting therapeutic ultrasound from an external emitter in a direction generally towards the target region of tissue, the therapeutic ultrasound enhancing gene transfection;

monitoring a signal from an ultrasound receiver positioned on the distal end of the catheter; and

adjusting the direction of the therapeutic ultrasound emitted from the external emitter in response to the strength of the signal from the ultrasound receiver such that the therapeutic ultrasound emitted by the external emitter targets the target region of tissue.

30. A method for inhibiting intimal hyperplasia, comprising:

emitting therapeutic ultrasound from an external emitter in a direction generally towards a target region of tissue, the therapeutic ultrasound inhibiting intimal hyperplasia;

monitoring a signal from an ultrasound receiver positioned on the distal end of a catheter disposed in the target regio of tissue; and

adjusting the direction of the therapeutic ultrasound emitted from the external emitter in response to the strength of the signal from the ultrasound receiver such that the therapeutic ultrasound emitted by the external emitter targets the target region of tissue.

31. A system for therapeutic ultrasound, comprising:

a cylindrical surface containing multiple transducer elements on one or more longitudinally parallel banks; and

a water path housing to couple ultrasonic emission to a patient.

32. The system of claim 31, wherein transducer elements on any one bank have intersecting beams.

33. The system of claim 32, wherein the intersecting beams intersect at a common point.

34. The system of claim 31, wherein the transducers on parallel banks are sized and positioned to generate an essentially uniform exposure of ultrasound within the subject.

35. The system of claim 31, wherein individual transducers are energized separately.

36. The system of claim 31, wherein individual transducers of a single bank are energized at the same time.

37. The system of claim 36, wherein the individual transducers are energized at the same frequency but with fixed and variable phases.

38. The system of claim 36, wherein the individual transducers are energized at different frequencies.

39. The system claim 31, wherein individual banks of transducers are interleaved to allow for closer packing of transducer banks for greater uniformity of exposure in the longitudinal direction.

40. A combined system for therapeutic ultrasound, comprising:

a catheter having an ultrasound receiver poisoned at its distal end;

an external therapeutic ultrasound transducer positioned on the skin of the subject;

a control system which provides feedback from the internal catheter sensor to the external therapeutic array.

41. A method of therapeutic ultrasound, comprising:

a catheter having an ultrasound receiver positioned at its distal end;

an external ultrasonic delivery system comprising many phased array elements;

a controller system;

whereby the controller system measures the time of acoustic propagation from each element on the phased array;

whereby further the controller system adjusts the transient times and phases of the phased array elements to direct the ultrasonic beam toward the receiving transducer on the catheter;

whereby further the controller system adjusts the transient times and phases of the phased array elements to sweep the ultrasonic beam in the general proximity of the receiving transducer on the catheter.