Methods for extracting substances using alternating current

• US 6,496,728 B2
• Filed: 02/13/2001
• Issued: 12/17/2002
• Est. Priority Date: 02/18/2000
• Status: Expired due to Fees

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Song, Yang, Higuchi, William I., Li, S. Kevin, Zhu, Honggang
• Primary Examiner(s): Derakshani, Philippe
• Application Number:
  US09/783,696
• Publication Number:
  US 20010044617A1
• Time in Patent Office: 672 Days
• Field of Search: 604/20, 128/803
• US Class Current: 604/20
• CPC Class Codes: A61N 1/0432 Anode and cathode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0448 Drug reservoir
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428

Abstract

A variety of methods for extracting different substances such as endogenous substances, pharmaceutical substances, markers of disease, and their metabolites across a tissue are provided. The methods utilize an AC signal to maintain a substantially constant electrical state in a region of the tissue through which extraction occurs, thereby allowing substances to be transported across the tissue in a controlled and predictable manner. Certain methods include an optional AC or DC prepulse signal to initially achieve the target electrical state. An optional DC offset signal can also be utilized to assist in promoting extraction of the substance. The methods have utility in a variety of different clinical settings and applications.

Claims

1. A method for extracting a substance from a body through a tissue, comprising:

(a) supplying one or more electrical signals, the one or more electrical signals comprising an AC signal;

(b) applying the AC signal to the tissue; and

(c) adjusting the AC signal so as to maintain a substantially constant electrical state within a region of the tissue, wherein maintenance of the substantially constant electrical state facilitates extraction of the substance.

2. The method of claim 1, wherein the AC signal is adjusted to maintain a substantially constant state of electroporation in the region of the tissue throughout the time period in which the substance is extracted.

3. The method of claim 1, wherein the electrical state is electrical conductance or electrical resistance and the AC signal is adjusted to maintain a substantially constant electrical conductance or electrical resistance in the region of the tissue throughout the time period in which the substance is extracted.

4. The method of claim 1, wherein the waveform of the AC signal is symmetric.

5. The method of claim 1, wherein the waveform of the AC signal is asymmetric.

6. The method of claim 1, wherein the shape of the AC signal waveform is square, sinusoidal, saw-tooth, triangular or trapezoidal.

7. The method of claim 1, wherein the frequency of the AC signal is at least about 1 Hz.

8. The method of claim 1, wherein the frequency of the AC signal is in the range of about 1 Hz to about 1 kHz.

9. The method of claim 1, wherein the frequency of the AC signal is in the range of about 1 kHz to about 30 kHz.

10. The method of claim 1, wherein the one or more electrical signals further comprise an electrical prepulse applied to the tissue prior to the AC signal to induce electroporation within the region.

11. The method of claim 1, wherein the voltage of the electrical prepulse is in the range of about 1 to about 90 V.

12. The method of claim 11, wherein the voltage of the electrical prepulse is in the range of about 5 to about 20 V.

13. The method of claim 11, wherein the voltage of the electrical prepulse is in the range of about 20 to about 40 V.

14. The method of claim 11, wherein the voltage of the electrical prepulse is in the range of about 40 to about 90 V.

15. The method of claim 11, wherein the electrical prepulse is a DC prepulse.

16. The method of claim 11, wherein the electrical prepulse is an AC prepulse.

17. The method of claim 12, wherein the electrical prepulse is a DC prepulse.

18. The method of claim 12, wherein the electrical prepulse is an AC prepulse.

19. The method of claim 1, wherein extraction of the substance is via passive diffusion through the electroporated region.

20. The method of claim 1, wherein.

(a) the one or more electrical signals further comprise a DC offset signal; and

(b) the applying step comprises applying the DC offset signal to the tissue, wherein the DC offset signal is effective to promote extraction of the substance through the region.

21. The method of claim 20, wherein the DC offset signal is applied substantially continuously during extraction of the substance and is of a voltage or current effective to control the rate of extraction of the substance through the region.

22. The method of claim 20, wherein the voltage of the DC offset signal is in the range of about 0.1 V to about 5 V or the current range of about 0.01 to about 0.5 mA/cm².

23. The method of claim 20, wherein the AC signal and the DC offset signal are provided simultaneously.

24. The method of claim 20, wherein the DC offset signal is applied after initiation of the AC signal.

25. The method of claim 20, wherein the DC offset signal is applied utilizing two electrodes in contact with the tissue and the direction of current flow of the DC offset signal is periodically reversed between the two electrodes.

26. The method of claim 1, wherein:

(a) the one or more electrical signals further comprise an electrical prepulse and a DC offset signal;

(b) applying comprises

(i) applying the electrical prepulse to the tissue prior to the AC signal to induce electroporation within the region; and

(ii) applying the DC offset signal to the tissue, wherein the DC offset signal promotes extraction of the substance through the region.

27. The method of claim 26, wherein the voltage of the electrical prepulse is in the range of about 1 to about 90 V.

28. The method of claim 27, wherein the electrical prepulse is a DC prepulse.

29. The method of claim 27, wherein the electrical prepulse is an AC prepulse.

30. The method of claim 26, wherein the DC offset signal is applied substantially continuously during extraction of the substance and is of a voltage or current effective to maintain a substantially constant rate of extraction of the substance through the region.

31. The method of claim 26, wherein the DC offset signal is applied utilizing two electrodes in contact with the tissue and the direction of current flow of the DC offset signal is periodically reversed between the two electrodes.

32. The method of claim 3, wherein the conductance or resistance within the region is maintained within a range that is approximately 20% of a target conductance or resistance.

33. The method of claim 32, wherein the range is approximately 10% of the target conductance or resistance.

34. The method of claim 33, wherein the range is approximately 5% of the target conductance or resistance.

35. The method of claim 34, wherein the range is approximately 1% of the target conductance or resistance.

36. The method of claim 1, wherein the tissue is human skin.

37. The method of claim 1, wherein the tissue is a human mucosal membrane.

38. The method of claim 1, wherein the tissue is an animal tissue other than a human tissue.

39. The method of claim 1, wherein the tissue is a plant tissue.

40. The method of claim 1, wherein the region has an area in the range of about 1 cm² to about 200 cm².

41. The method of claim 40, wherein the region has an area in the range of about 5 cm² to about 100 cm².

42. The method of claim 41, wherein the region has an area in the range of about 5 cm² to about 30 cm².

43. The method of claim 1, wherein the substance is an uncharged substance.

44. The method of claim 43, wherein the substance is glucose.

45. The method of claim 43, wherein the substance is ethanol.

46. The method of claim 1, wherein the substance is charged.

47. The method of claim 46, wherein the substance is negatively charged.

48. The method of claim 46, wherein the substance is positively charged.

49. The method of claim 1, wherein the substance is a substance correlated with a metabolic disorder.

50. The method of claim 49, wherein the substance is phenylalanine.

51. A method for extracting a substance from the body of a human patient through a tissue, comprising:

(a) supplying one or more electrical signals, the one or more electrical signals comprising an AC signal;

(b) applying the AC signal to the tissue, wherein the tissue is human skin or mucosal tissue; and

(c) adjusting the AC signal so as to maintain a substantially constant state of electroporation within a region of the tissue throughout the time during which extraction occurs, wherein maintenance of the substantially constant state of electroporation promotes extraction of the substance.

52. The method of claim 51, further comprising applying an electrical prepulse applied to the tissue prior to the AC signal to induce electroporation within the region.

53. The method of claim 51, further comprising applying a DC offset signal effective to promote extraction of the substance through the region.

54. The method of claim 52, further comprising applying a DC offset signal effective to promote extraction of the substance through the region.