Method and apparatus for in-vivo transdermal and/or intradermal delivery of drugs by sonoporation

• US 6,487,447 B1
• Filed: 10/17/2000
• Issued: 11/26/2002
• Est. Priority Date: 10/17/2000
• Status: Expired due to Term

• Current Assignee: Ultra Sun Technology Inc.
• Original Assignee: Ultra Sun Technology Inc.
• Inventors: Weimann, Ludwig, Childs, Richard
• Primary Examiner(s): Look, Edward K.
• Assistant Examiner(s): LESLIE, MICHAEL S
• Application Number:
  US09/690,604
• Time in Patent Office: 770 Days
• Field of Search: 604/20, 604/22, 606/9
• US Class Current: 604/20
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

An apparatus for performing in-vivo sonoporation of a skin area and transdermal and/or intradermal delivery of a drug solution includes a container having an end covered with a porous membrane and containing the drug solution and an ultrasound horn having a tip submerged in the drug solution. The ultrasound horn applies ultrasound radiation to the drug solution. The ultrasound radiation has a frequency in the range of 15 KHz and 1 MHz and is applied at an intensity, for a period of time and at a distance from said skin area effective to generate cavitation bubbles. The cavitation bubbles collapse and transfer their energy into the skin area thus causing the formation of pores in the skin area. The ultrasound radiation intensity and distance from the skin area are also effective in generating ultrasonic jets, which ultrasonic jets then drive the drug solution through the porous membrane and the formed pores into the skin.

Claims

1. An apparatus for performing in-vivo sonoporation of a skin area and transdermal and/or intradermal delivery of a drug solution comprising:

a container having an end covered with a porous membrane and containing said drug solution;

an ultrasound horn having a tip submerged in said drug solution and applying ultrasound radiation to said drug solution wherein said ultrasound radiation has a frequency in the range of 15 KHz and 1 MHz and is applied at an intensity, for a period of time and at a distance from said skin area effective to generate cavitation bubbles, wherein said cavitation bubbles collapse and transfer their energy into the skin area thus causing the formation of pores in the skin area; and

wherein said ultrasound radiation intensity and distance from the skin area are also effective in generating ultrasonic jets, said ultrasonic jets driving said drug solution through said porous membrane and said formed pores into the skin area.

2. The apparatus of claim 1 wherein said membrane has pores with a diameter in the range of 10 to 100 micrometers.

3. The apparatus of claim 1 wherein said membrane is hydrophobic.

4. The apparatus of claim 1 wherein said tip is removable connected to said ultrasound horn.

5. The apparatus of claim 1 wherein said tip comprises a flat distal end surface.

6. The apparatus of claim 1 wherein said tip comprises a concave distal end surface.

7. The apparatus of claim 1 wherein said tip comprises a distal end surface having a plurality of depressions.

8. The apparatus of claim 1 wherein said tip comprises a body having markings indicating the amount of the drug solution contained in the container.

9. The apparatus of claim 1 further comprising a removable protective film covering said membrane.

10. The apparatus of claim 1 wherein said container comprises:

an outer wall;

an inner wall; and

an absorbent wick placed between said inner and outer wall, said wick absorbing any excess drug solution that is not driven into the skin area through the formed pores.

11. The apparatus of claim 10 wherein said wick comprises a highly absorbent and hydrophilic material selected from the group consisting of absorbent cellulose material, polyvinyl alcohol sponge, Sodium Carboxy-Methyl Cellulose (CMC), and blotting paper.

12. The apparatus of claim 10 wherein said inner wall comprises first and second grooves, said tip comprises a body having first and second grooves and wherein said first and second grooves of the tip body are arranged opposite said first and second grooves of the container inner wall, the arrangement defining first and second spaces for accommodating first and second o-rings, respectively.

13. The apparatus of claim 10 wherein said container further comprises an inlet septum for filling said container with the solution.

14. The apparatus of claim 10 wherein said wick comprises a spongy material having highly absorbent and hydrophilic properties.

15. The apparatus of claim 1 wherein said container is a cylinder.

16. The apparatus of claim 1 wherein said container comprises a transparent material.

17. The apparatus of claim 1 wherein said container comprises a plastic material.

18. The apparatus of claim 1 wherein said ultrasound frequency is 20 KHz.

19. The apparatus of claim 1 wherein said ultrasound intensity is in the range of 5 W/cm² and 55 W/ cm².

20. The apparatus of claim 1 wherein said tip has a distal end located at a distance from said membrane in the range of 1 millimeter to 10 millimeters.

21. The apparatus of claim 1 wherein said ultrasound radiation is continuous.

22. The apparatus of claim 1 wherein said ultrasound radiation is pulsed.

23. The apparatus of claim 1 wherein said period of time is in the range of about 30 seconds to 5 minutes of continuous exposure to said ultrasound radiation.

24. The apparatus of claim 1 wherein said period of time is in the range of about 10 minutes to 20 minutes of pulsed exposure to said ultrasound radiation with a 5% duly cycle.

25. The apparatus of claim 1 wherein said formed pores have a diameter in the range of 1 micrometer to 100 micrometers.

26. A method of performing in-vivo sonoporation of a skin area and transdermal and/or intradermal delivery of a drug solution comprising:

providing a container containing a predetermined amount of said drug solution and having a first end and a second end, said second end being covered with a porous membrane;

submerging a tip of an ultrasound horn in said drug solution through said first end of the container;

placing said porous membrane in contact with said skin area; and

applying ultrasound radiation to said drug solution wherein said ultrasound radiation has a frequency in the range of 15 KHz and 1 MHz and is applied at an intensity, for a period of time and at a distance from said skin area effective to generate cavitation bubbles, wherein said cavitation bubbles collapse and transfer their energy into the skin area thus causing the formation of pores in the skin area; and

wherein said ultrasound radiation intensity and distance from the skin area are also effective in generating ultrasonic jets, said ultrasonic jets driving said drug solution through said porous membrane and said formed pores into the skin area.

27. The method of claim 26 wherein said membrane has pores with a diameter in the range of 10 to 100 micrometers.

28. The method of claim 26 wherein said membrane is hydrophobic.

29. The method of claim 26 wherein said tip is removable connected to said ultrasound horn comprising before submerging said tip in said drug solution attaching said tip to said ultrasound horn.

30. The method of claim 29 further comprising sterilizing said tip before attaching it to said ultrasound horn.

31. The method of claim 26 wherein said tip comprises a flat distal end surface.

32. The method of claim 26 wherein said tip comprises a concave distal end surface.

33. The method of claim 26 wherein said tip comprises a distal end surface having a plurality of depressions.

34. The method of claim 26 wherein said tip comprises a body having markings indicating the amount of the drug solution contained in the container.

35. The method of claim 34 further comprising checking the amount of said drug solution contained in the container before applying said ultrasound radiation.

36. The method of claim 35 further comprising adding drug solution to said container.

37. The method of claim 26 wherein a removable protective film covers said membrane further comprising removing said covering before placing said membrane in contact with the skin area.

38. The method of claim 26 wherein said container comprises:

an outer wall;

an inner wall; and

an absorbent wick placed between said inner and outer wall, said wick absorbing any excess drug solution that is not driven into the skin area through the formed pores.

39. The method of claim 26 wherein said ultrasound frequency is 20 KHz.

40. The method of claim 26 wherein said ultrasound intensity is in the range of 5 W/cm² and 55 W/ cm².

41. The method of claim 26 wherein said tip has a distal end located at a distance from said membrane in the range of 1 millimeter to 10 millimeters.

42. The method of claim 26 wherein said ultrasound radiation is continuous.

43. The method of claim 26 wherein said ultrasound radiation is pulsed.

44. The method of claim 26 wherein said period of time is in the range of about 30 seconds to 5 minutes of continuous exposure to said ultrasound radiation.

45. The method of claim 26 wherein said period of time is in the range of about 10 minutes to 20 mutes of pulsed exposure to said ultrasound radiation with a 5% duty cycle.

46. The method of claim 26 wherein said formed pores have a diameter in the range of 1 micrometer to 100 micrometers.