Methods and systems for the inhibition of vascular hyperplasia

• US 6,210,393 B1
• Filed: 12/30/1998
• Issued: 04/03/2001
• Est. Priority Date: 12/31/1997
• Status: Expired due to Fees

• Current Assignee: PharmaSonics, Inc.
• Original Assignee: PharmaSonics, Inc.
• Inventors: Brisken, Axel F.
• Primary Examiner(s): NGUYEN, ANH TUAN TUONG
• Application Number:
  US09/223,230
• Time in Patent Office: 825 Days
• Field of Search: 600/467, 600/471, 600/459, 600/464, 600/466, 601/2, 604/22, 604/65, 604/67, 604/104, 604/158, 604/164, 604/508, 604/509, 604/510, 604/513, 128/898, 606/108, 606/198, 623/1
• US Class Current: 604/508
• CPC Class Codes: A61B 17/2202 the ultrasound transducer being inside patient's body at the distal end of the catheter
• CPC Class Codes: A61B 2017/22002 preventing restenosis
• CPC Class Codes: A61B 2017/22052 eccentric
• CPC Class Codes: A61B 50/30 Containers specially adapted for packaging, protecting, dispensing, collecting or disposing of surgical or diagnostic appliances or instruments for wound clamps A61B17/10; for ligaturing clips A61B17/122; packages or dispensers for surgical gloves or finger-stalls A61B42/40
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61F 2007/0091 inflatable
• CPC Class Codes: A61N 7/022 intracavitary

Abstract

Post-interventional neointimal hyperplasia in arteries is treated by the application of ultrasonic energy. Usually, an intravascular catheter having an interface surface is positioned at a target site in the artery which has previously been treated. The interface surface is vibrationally excited to apply energy to the arterial wall in a manner which inhibits smooth muscle cell proliferation in the neointimal layer.

Claims

1. A method for treating an arterial stenosis, said method comprising:

implanting a stent within an artery at a target site of arterial stenosis; and

exposing the site to vibrational energy at a combination of mechanical index and time sufficient to inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia at said site but which does not produce cavitation at the target site.

2. A method as in claim 1, wherein the vibrational energy travels to the arterial wall in a direction which is substantially free of an axial component.

3. A method as in claim 1, wherein the vibrational energy causes a temperature rise below 10°

C. in the wall of the artery.

4. A method as in claim 1, wherein the vascular smooth muscle cells at least mostly remain viable but in a quiescent state in the neointimal layer after exposure to the vibrational energy.

5. A method as in claim 1, wherein migration of vascular smooth muscle cells into the neointimal layer is not substantially inhibited.

6. A method as in claim 1, wherein viability of vascular smooth muscle cells in a medial layer of the artery is not significantly inhibited.

7. A method as in claim 1, wherein vascular smooth muscle cell proliferation in the neointimal layer exposed to vibrational energy is inhibited by at least 2% after seven days in comparison to such proliferation in a neointimal layer not exposed to the vibrational energy.

8. A method as in claim 1, wherein the cross-sectional area of the neointimal layer which has been exposed to vibrational energy is inhibited by at least 10% after 28 days in comparison to the cross-sectional area of a neointimal layer not exposed to the vibrational energy.

9. A method as in claim 1, wherein the vibrational energy has a frequency in the range from 100 kHz to 5 MHz.

10. A method as in claim 9, wherein the intensity is in the range from 0.01 W/cm² to 100 W/cm².

11. A method as in claim 10, wherein the frequency and intensity are selected to produce a mechanical index at the neointimal wall in the range from 0.2 to 10.

12. A method as in claim 11, wherein the mechanical index at the neointimal wall is in the range from 0.5 to 5.

13. A method as in claim 10, wherein the intensity is in the range from 0.1 W/cm² to 20 W/cm².

14. A method as in claim 13, wherein the intensity is in the range from 0.5 W/cm² to 5 W/cm².

15. A method as in claim 9, wherein the vibrational energy has a frequency in the range from 300 kHz to 3 MHz.

16. A method as in claim 15, wherein the vibrational energy has a frequency in the range from 500 kHz to 1.5 MHz.

17. A method as in claim 1, wherein the vibrational energy is directed against the arterial wall with a pulse repetition frequency (PRF) in the range from 10 Hz to 10 kHz.

18. A method as in claim 1, wherein the energy is directed against the arterial wall with a duty cycle in the range from 0.1 to 100 percent.

19. A method as in claim 1, wherein the exposing step comprises:

intravascularly introducing an interface surface to the target site within the artery; and

ultrasonically driving the interface surface to radiate ultrasonic energy into the arterial wall adjacent the target site.

20. A method as in claim 19, wherein the introducing step comprises:

providing a flexible catheter having at least one ultrasonic transducer disposed near its distal end;

energizing the ultrasonic transducer, wherein the transducer drives the interface surface.

21. A method as in claim 20, wherein the interface surface directly contacts the arterial wall at the target site.

22. A method as in claim 20, wherein the interface surface is spaced-apart from the arterial wall, wherein the ultrasonic energy is transmitted through a liquid medium disposed between the interface surface and the arterial wall.

23. A method as in claim 22, wherein the liquid medium is entrapped within a balloon which is inflated against the arterial wall.

24. A method as in claim 19, wherein the ultrasonically driving step comprises vibrating the surface in a radial direction.

25. A method as in claim 19, wherein the ultrasonically exciting step comprises vibrating the surface in an axial direction.

26. A method as in claim 17, wherein the PRF is in the range from 100 Hz to 5 kHz.

27. A method as in claim 26, wherein the PRF is in the range from 300 Hz to 3 kHz.

28. A method as in claim 18, wherein the duty cycle is in the range from 0.2 to 10 percent.

29. A method as in claim 28, wherein the duts cycle is in the range from 0.2 to 2 percent.