Methods and systems for the inhibition of vascular hyperplasia

• US 6,503,243 B1
• Filed: 09/01/2000
• Issued: 01/07/2003
• 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:
  US09/653,033
• Time in Patent Office: 858 Days
• Field of Search: 604/22, 604/65, 604/67, 604/35, 604/104, 604/158, 604/164, 604/508, 604/509, 604/500, 604/510, 604/513, 606/108, 606/198, 623/1.11, 623/1.15, 623/1.42, 600/1, 600/3, 600/467, 600/471, 128/878
• 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 frequency in the range from 100 kHz to 5 MHz, a mechanical index in the range from 0.1 to 50, and a pulse repetition frequency (PRF) in the range from 10 Hz to 10 kHz, in order to inhibit said intimal hyperplasia.

2. A method as in claim 1, wherein the vibrational energy has a frequency in the range from 300 kHz to 3 MHz.

3. A method as in claim 1, wherein the frequency and intensity are selected to produce a mechanical index at the neointimal wall in the range from 0.2 to 10.

4. A method as in claim 3, wherein the vibrational energy is directed against the arterial wall with a pulse repetition frequency (PRF) in the range from 100 Hz to 5 kHz.

5. A method as in claim 4, wherein the energy is directed against the arterial wall with a duty cycle in the range from 0.1 to 100 percent.

6. A method as in claim 5, wherein the energy is directed with a duty cycle in the range from 0.2 to 10%.

7. A method as in claim 1, wherein the elapsed treatment time is in the range from 10 to 900 seconds.

8. A method as in claim 1, wherein the intensity is in the range from 0.01 W/cm² to 100 W/cm².

9. A method as in any of claims 1-8, wherein the vibrational energy comprises pressure waves which travel to the arterial wall in substantially radial direction.

10. A method as in any of claims 1-8, wherein exposing the target site comprises:

positioning an interface surface on or coupled to a vibrational transducer at the target site at a risk of neointimal hyperplasia in the artery; and

driving the transducer to direct vibrational energy from the interface surface against the arterial wall.

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

12. A method as in any of claims 1-8, wherein the vibrational energy causes a temperature rise below 10°

C. in the wall of the artery.

13. A method as in any of claims 1-8, 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.

14. A method as in any of claims 1-8, wherein migration of vascular smooth muscle cells into the neointimal layer is not substantially inhibited.

15. A method as in any of claims 1-8, wherein viability of vascular smooth muscle cells in a medial layer of the artery is not significantly inhibited.

16. A method as in any of claims 1-8, 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.

17. A method as in any of claims 1-8, 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.

18. A method as in claim 10, 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.

19. A method as in claim 18, wherein the interface surface directly contacts the arterial wall at the target site.

20. A method as in claim 18, 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.

21. A method as in claim 20, wherein the liquid medium is entrapped within a balloon which is inflated against the arterial wall.

22. A method as in claim 10, wherein the ultrasonically driving step comprises vibrating the surface in a radial direction.

23. A method as in claim 10, wherein the ultrasonically exciting step comprises vibrating the surface in an axial direction.