Methods and apparatus for uniform transcutaneous therapeutic ultrasound

• US 20030229331A1
• Filed: 01/10/2003
• Published: 12/11/2003
• Est. Priority Date: 11/05/1999
• Status: Abandoned Application

• Current Assignee: PharmaSonics, Inc.
• Original Assignee: PharmaSonics, Inc.
• Inventors: Cowan, Mark W., Brisken, Axel F., Zuk, Robert, McKenzie, John
• Application Number:
  US10/340,574
• Publication Number:
  US 20030229331A1
• Time in Patent Office: Days
• US Class Current: 604/500
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

A wide beam ultrasound delivery system providing a uniform exposure field is used to enhance the uptake of injected substances and/or to enhance the transfection of DNA in the tissues of human subject, or reduce the amount of vascular intimal hyperplasia in human subjects following vascular injury.

Claims

1. A method of enhancing cellular absorption of a substance delivered into a target region of a patient'"'"'s body, comprising:

delivering the substance into the target region;

applying a uniform field of ultrasound energy across a wide area of the target region, the ultrasound energy being of a type and an amount sufficient to enhance cellular absorption of the substance into the target region; and

the ultrasound energy being of a type and an amount sufficient to enhance transfection of the DNA in the target region, wherein the uniform field comprises

a field which varies in intensity by at least one of (1) less than 10 dB in a lateral direction across the width of the field, and (2) less than 10 dB in an axial direction across the depth of the target region.

2. The method of claim 1, wherein the ultrasound energy is sufficiently strong to cause cellular absorption, yet is sufficiently weak to prevent cell lysis.

3. The method of claim 1, wherein the substance is injected intramuscularly as a bolus into the target region.

4. The method of claim 1, wherein the uniform field comprises a field which varies in intensity by less than 10 dB in a lateral direction across the width of the field.

5. The method of claim 1, wherein the uniform field comprises a field which varies in intensity by less than 6 dB in a lateral direction across the width of the field.

6. The method of claim 1, wherein the uniform field comprises a field which varies in intensity by less than 3 dB in a lateral direction across the width of the field.

7. The method of claim 1, wherein the uniform field comprises a field which varies in intensity by less than 10 dB in an axial direction across the depth of the target region.

8. The method of claim 1, wherein the uniform field comprises a field which varies in intensity by less than 6 dB in an axial direction across the depth of the target region.

9. The method of claim 1, wherein the uniform field comprises a field which varies in intensity by less than 6 dB in an axial direction across the depth of the target region.

10. The method of claim 1, wherein a uniform field comprises a field which varies in intensity by less than 3 dB in an axial direction across the depth of the target region.

11. The method of claim 1, wherein the ultrasound energy has a mechanical index of 0.1 to 20.

12. The method of claim 1, wherein the ultrasound energy has a mechanical index of 0.3 to 15.

13. The method of claim 1, wherein the ultrasound energy has a mechanical index of 0.5 to 10.

14. The method of claim 1, wherein the ultrasound energy has a transient thermal index less than 4.

15. The method of claim 1, wherein the ultrasound energy is applied with a duty cycle of 0.1 to 50%.

16. The method of claim 1, wherein the ultrasound energy is applied with a duty cycle of 0.3 to 20%.

17. The method of claim 1, wherein the ultrasound energy is applied with a duty cycle of 0.5 to 5%.

18. The method of claim 1, wherein the ultrasound energy is applied at a frequency of 20 kHz to 5 MHz.

19. The method of claim 1, wherein the ultrasound energy is applied at frequency of 100 kHz to 1.5 MHz.

20. The method of claim 1, wherein the ultrasound energy field has a beam width of at least 0.5 cm.

21. The method of claim 1, wherein the ultrasound energy field has a beam width of at least 1.2 cm.

22. The method of claim 1, wherein the ultrasound energy field has a beam width of at least 3.5 cm.

23. The method of claim 1, wherein the target region has a transdermal depth of 1 to 4 cm.

24. The method of claim 1, wherein the uniform field of ultrasound energy is applied across the wide area of the target region by a wide beam ultrasound delivery system comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

an ultrasound transducer mounted within the housing; and

an acoustic couplant material in contact with at least one side of the transducer, and in contact with the skin-contact window.

25. The method of claim 1, wherein the uniform field of ultrasound energy is applied across the wide area of the target region concurrently with delivering the substance into the target region.

26. The method of claim 1, wherein the uniform field of ultrasound energy is applied across the wide area of the target region before delivering the substance into the target region.

27. The method of claim 1, wherein the uniform field of ultrasound energy is applied across the wide area of the target region immediately after delivering the substance into the target region.

28. The method of claim 1, wherein the uniform field of ultrasound energy is applied across the wide area of the target region 15 to 60 minutes after delivering the substance into the target region.

41. A kit for enhancing cellular absorption of a substance delivered into a target region of a patient'"'"'s body, comprising:

an ultrasound energy delivery system; and

instructions for use setting forth the method of claim 1.

29. A method of inhibiting vascular intimal hyperplasia, comprising:

applying a uniform field of ultrasound energy across a wide area of a patient'"'"'s vasculature, the ultrasound energy being of a type and an amount sufficient to inhibit vascular intimal hyperplasia.

30. The method of claim 29, wherein the ultrasound energy is applied at a frequency of 100 kHz to 5 MHz.

31. The method of claim 29, wherein the ultrasound energy is applied at a mechanical index of 0.1 to 50.

32. The method of claim 29, wherein the ultrasound energy is applied with a duty cycle of 0.1 to 100%.

33. The method of claim 29, wherein the ultrasound energy is applied at a frequency of 100 kHz to 5 MHz and an intensity of 0.1 W/cm2 to 100 W/cm2.

42. A kit for inhibiting vascular intimal hyperplasia, comprising:

an ultrasound energy delivery system; and

instructions for use setting forth the method of claim 29.

34. A wide beam uniform field ultrasound energy delivery system, comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

a plurality of ultrasound transducers mounted within the housing; and

an acoustic couplant material in contact with at least one side of the transducers, and in contact with the skin-contact window.

35. The wide beam uniform field ultrasound energy delivery system of claim 34, wherein the transducers comprise a plurality of concentric annular-shaped elements, disposed one within another.

36. The wide beam uniform field ultrasound energy delivery system of claim 34, further comprising:

electronic driving circuitry adapted to individually control the operation of each of the transducers.

37. A wide beam uniform field ultrasound delivery system, comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

a two-dimensional array of individual flat-plate transducer elements mounted within the housing; and

an acoustic couplant material in contact with at least one side of each of the individual transducers, and in contact with the skin-contact window.

38. The wide beam uniform field ultrasound delivery system of claim 37, wherein the individual flat plate transducer elements are angled to one another to provide coverage of the ultrasound field over a wide area.

39. The wide beam uniform field ultrasound delivery system of claim 37, further comprising:

electronic driving circuitry adapted to individually control the operation of each of the transducers.

40. A wide beam uniform field ultrasound delivery system, comprising:

a two-dimensional array of individual flat-plate transducer elements which is adapted to be coupled directly to the patient, with no intermediate fluid coupling.

43. A wide beam uniform field ultrasound delivery system comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

an ultrasound transducer mounted within the housing;

an acoustic couplant material in contact with at least one side of the transducer, and in contact with the skin-contact window;

a first adjustable mount connecting the transducer to the interior of the housing, the first adjustable mount adapted to articulate the transducer for back-and-forth movement of a beam of ultrasound energy in a first direction; and

a second adjustable mount connecting the transducer to the interior of the housing, the second adjustable mount adapted to articulate the transducer for back-and-forth movement of the beam of ultrasound energy in a second direction, the second direction being perpendicular to the first direction.

44. A wide beam uniform field ultrasound delivery system comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

an ultrasound transducer mounted within the housing; and

an acoustic couplant material in contact with at least one side of the transducer, and in contact with the skin-contact window, wherein the transducer is centrally located in the housing and the acoustically reflective surface is disposed around the interior periphery of the housing.

45. A wide beam uniform field ultrasound delivery system comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

an ultrasound transducer mounted within the housing; and

an acoustic couplant material in contact with at least one side of the transducer, and in contact with the skin-contact window, wherein the acoustically reflective surface is centrally located in the housing and the transducer is disposed around the interior periphery of the housing.

46. A wide beam uniform field ultrasound delivery system comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

an ultrasound transducer mounted within the housing; and

an acoustic couplant material in contact with at least one side of the transducer, and in contact with the skin-contact window, wherein the transducer further comprises an acoustic refractive material covering the side of the transducer disposed in contact with the acoustic coupling material.

47. A wide beam uniform field ultrasound delivery system comprising:

a housing having an opening at a distal end;

a skin-contact window covering the opening;

an ultrasound transducer mounted within the housing; and

an acoustic couplant material in contact with at least one side of the transducer, and in contact with the skin-contact window, wherein the skin-contact window has a curved shape to narrow a beam of ultrasound energy passing therethrough.