Methods and systems for the inhibition of vascular hyperplasia

• US 6,494,874 B1
• Filed: 09/01/2000
• Issued: 12/17/2002
• 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, Anhtuan T.
• Application Number:
  US09/653,678
• Time in Patent Office: 837 Days
• Field of Search: 604/22, 604/35, 604/65, 604/67, 604/104, 604/158, 604/164, 604/508, 604/509, 604/500, 604/510, 604/513, 606/108, 606/198, 600/1, 600/3, 600/467, 600/471, 623/1.11, 623/1.15, 623/1.42, 128/898
• 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 inhibiting neointimal hyperplasia in an artery, said method comprising:

exposing a target site at risk of neointimal hyperplasia within the artery to vibrational energy at a mechanical index and for a time sufficient to inhibit said intimal hyperplasia, wherein the vibrational energy comprises pressure waves which travel to the arterial wall in a substantially radial direction.

2. A method as in claim 1, wherein the direction of the pressure waves is substantially free of an axial component.

3. 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 vibrate the interface surface in a radial direction and radiate ultrasonic energy into the arterial wall adjacent the target site.

4. A method as in claim 3, 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.

5. A method as in claim 4, wherein the interface surface directly contacts the arterial wall at the target site.

6. A method as in claim 4, 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.

7. A method as in claim 6, wherein the liquid medium is entrapped within a balloon which is inflated against the arterial wall.

8. A method as in any of claims 1-7, wherein the vibrational energy does not cause significant cavitation.

9. A method as in any of claims 1-7, wherein the vibrational energy causes a temperature rise below 10°

C. in the wall of the artery.

10. A method as in any of claims 1-7, 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.

11. A method as in any of claims 1-7, wherein migration of vascular smooth muscle cells into the neointimal layer is not substantially inhibited.

12. A method as in any of claims 1-7, wherein viability of vascular smooth muscle cells in a medial layer of the artery is not significantly inhibited.

13. A method as in any of claims 1-7, 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.

14. A method as in any of claims 1-7, wherein the area of the neointimal layer exposed to vibrational energy is inhibited by at least 10% after 28 days in comparison to the area of a neointimal layer not exposed to the vibrational energy.

15. A method as in any of claims 1-7, wherein the vibrational energy has a frequency in the range from 100 kHz to 5 MHz.

16. A method as in claim 15, wherein the intensity is in the range from 0.01 W/cm² to 100 W/cm².

17. A method as in claim 16, wherein the frequency and intensity are selected to produce a mechanical index at the neointimal wall in the range from 0.1 to 50.

18. A method as in any of claims 1-7, 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.

19. A method as in any of claims 1-7, wherein the energy is directed against the arterial wall with a duty cycle in the range from 0.1 to 100 percent.