Transdermal drug delivery and analyte extraction

• US 6,711,435 B2
• Filed: 12/12/2001
• Issued: 03/23/2004
• Est. Priority Date: 11/09/1998
• Status: Expired due to Term

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Ltd.
• Inventors: Avrahami, Zohar
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US10/021,586
• Publication Number:
  US 20030097127A1
• Time in Patent Office: 832 Days
• Field of Search: 604/19-21, 607/2, 607/3, 607/152, 600/391, 600/372
• US Class Current: 604/20
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• 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
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

A device for ablating the stratum corneum epidermidis of a subject, including a plurality of electrodes, which are applied to the subject'"'"'s skin at respective points. A power source applies electrical energy between two or more of the plurality of electrodes, in order to cause ablation of the stratum corneum primarily in an area intermediate the respective points.

Claims

1. A device for ablating stratum corneum epidermidis of skin on the body of a subject, comprising:

a plurality of electrodes, which are adapted to be applied to the skin of the subject at respective points; and

a power source, which is adapted to apply electrical energy to the plurality of the electrodes so as to induce an electrical current to flow through the stratum corneum, causing ablation of narrow channels through the stratum corneum at the respective points.

2. A device according to claim 1, wherein the power source is adapted to apply the electrical energy such that skin layers beneath the stratum corneum are substantially not ablated.

3. A device according to claim 1, wherein the power source is adapted to apply the electrical energy such that the ablation of the narrow channels causes a puncturing of the stratum corneum.

4. A device according to claim 1, wherein the device is adapted to ablate the narrow channels in order to allow a substance to pass therethrough.

5. A device according to claim 4, wherein the device is adapted to ablate the narrow channels so as to allow the substance to pass through the skin into the body of the subject.

6. A device according to claim 5, and comprising a housing having a surface that defines a storage region adapted to store the substance in preparation for passage of the substance through the skin.

7. A device according to claim 4, wherein the device is adapted to ablate the narrow channels so as to allow the substance to pass through the skin from within the body.

8. A device according to claim 4, wherein the power source is adapted to apply the electrical energy during a first time period, so as to ablate the narrow channels in order to facilitate passage of the substance therethrough during a second time period, subsequent to the first time period.

9. A device according to claim 4, wherein the plurality of electrodes are arranged in an arrays wherein a density of the electrodes in the array is determined responsive to a desired transdermal transfer rate of the substance.

10. A device according to claim 1, wherein the power source is adapted to generate an electric field which causes a current to flow through the stratum corneum, and wherein the device is adapted to reduce power dissipated in the stratum corneum responsive to variation of a characteristic of the current.

11. A device according to claim 10, wherein the characteristic of the current is drawn from a list consisting of:

a magnitude of the current;

a time-integration of the current;

a first time-derivative of the current; and

a second time-derivative of the current.

12. A device according to claim 10, wherein the power source is adapted to modify the electric field so as to reduce current through one of the plurality of electrodes, substantially independently of the current through another one of the plurality of electrodes.

13. A device according to claim 10, and comprising a limited-conduction unit, wherein at least one of the plurality of electrodes is coupled to receive the current through the limited-conduction unit, which unit allows current below a threshold value to flow therethrough substantially unimpeded, and becomes substantially non-conductive if the current flowing therethrough exceeds a limited-conduction threshold value.

14. A device according to claim 10, and comprising an electrically-conductive dissolving element, wherein at least one of the plurality of electrodes is coupled to the electrically-conductive dissolving element, wherein the dissolving element is characterized by a dissolving rate generally proportional to the current passing therethrough, and wherein the dissolving element is adapted to become substantially nonconductive responsive to a function of the current.

15. A device according to claim 10, wherein the power source is adapted to modify the electric field such that the current through at least one of the plurality of electrodes is reduced responsive to the variation of the characteristic of the current through another one of the plurality of electrodes.

16. A device according to claim 10, and comprising a voltage sensing unit coupled to measure a voltage drop across two of the plurality of electrodes, and wherein the power source is adapted to modify the electric field so as to reduce the current responsive to the measurement made by the sensing unit.

17. A device according to claim 10, and comprising:

a resistive element coupled to one of the plurality of electrodes and to the power source; and

a voltage sensing unit coupled to measure a voltage drop across the resistive element in order to determine a current passing therethrough, wherein the power source comprises a voltage source, and wherein the voltage source is adapted to reduce a voltage thereof responsive to a measurement made by the sensing unit which indicates that the current through the resistive element is above a current-threshold value.

18. A device according to claim 10, wherein at least one of the plurality of electrodes is adapted to be printed directly on the skin and is adapted to become substantially electrically nonconductive responsive to the value of the current passing therethtough being greater than a threshold value.

19. A device according to claim 10, and comprising:

a capacitor, coupled to two of the plurality of electrodes; and

a switch, coupled to the power source and the capacitor, such that the switch, in a closed phase thereof, is adapted to allow current to flow from the power source to the capacitor and to the two electrodes, and such that the switch, in an open phase thereof, is adapted to substantially terminate current flow from the power source to the capacitor and to the two electrodes, wherein the power source is adapted to charge the capacitor during the closed phase, and wherein the capacitor is adapted to discharge current through the electrodes during the open phase.

20. A device according to claim 1, wherein the distance between two of the plurality of electrodes is less than about 0.3 mm.

21. A device according to claim 20, wherein the distance between the two electrodes is between about 0.01 mm and about 0.1 mm.

22. A device according to claim 1, wherein the plurality of the electrodes comprises a common electrode and a multiplicity of individual electrodes against the skin, and wherein the power source is adapted to apply the electrical energy so as to induce the current to flow between the plurality of individual electrodes and the common electrode.

23. A device according to claim 22, wherein the common electrode has a plurality of perforations therethrough, and wherein each of the individual electrodes passes through a respective perforation of the common on electrode.

24. A device according to claim 1, wherein the power source is adapted to generate alternating current, a frequency thereof being above about 100 Hz.

25. A device according to claim 24, wherein the power source is adapted to generate the alternating current such that the frequency is between about 1 kHz and about 300 kHz.

26. A device according to claim 1, wherein the power source is adapted to generate alternating current and to modulate a frequency thereof between a first frequency value and a second frequency value.

27. A device according to claim 1, wherein the power source is adapted to apply the electrical energy for less than about 1 second.

28. A device according to claim 27, wherein the power source is adapted to apply the electrical energy for less than about 200 milliseconds.

29. A device according to claim 1, wherein the electrodes comprise at least one set of two or more electrodes, and wherein the power source is adapted to apply the electrical energy so as to induce the current to flow between the electrodes in the at least one set.

30. A device for ablating stratum corneum epidermidis of skin on the body of a subject, comprising:

a housing having a surface that defines a storage region adapted to store an active substance;

a plurality of electrodes, which are adapted to be applied to the skin of the subject at respective points; and

a power source, which is adapted to apply electrical energy between two or more of the plurality of electrodes, to cause ablation of an area of the stratum corneum during a first time period, so as to facilitate passage of the active substance through the ablated area during a second time period, subsequent to the first time period.

31. A device according to claim 30, wherein the distance between two of the plurality of electrodes is less than about 0.3 mm.

32. A device according to claim 31, wherein the distance between the two electrodes is between about 0.01 mm and about 0.1 mm.

33. A device according to claim 30, wherein the plurality of the electrodes comprises a common electrode and a multiplicity of individual electrodes against the skin, and wherein the power source is adapted to apply the electrical energy so as to induce the current to flow between the plurality of individual electrodes and the common electrode.

34. A device according to claim 30, wherein the plurality of the electrodes comprises at least one set of two or more electrodes, and wherein the power source is adapted to apply the electrical energy so as to induce the current to flow between the electrodes in the at least one set.

35. A device according to claim 30, wherein the power source is adapted to generate alternating current, a frequency thereof being above about 100 Hz.

36. A device according to claim 35, wherein the power source is adapted to generate the alternating current such that the frequency is between about 1 kHz and about 300 kHz.

37. A device according to claim 35, wherein the first time period is less than about 1 second.

38. A device according to claim 37, wherein the first time period is less than about 200 milliseconds.

39. A device according to claim 30, wherein the plurality of electrodes are arranged in an array, wherein a density of the electrodes in the array is determined responsive to a desired transdermal transfer rate of the substance.

40. A device for ablating stratum corneum epidermidis of skin of a subject, comprising:

a plurality of electrodes, which are adapted to be applied to the skin of the subject at respective points, such that two of the electrodes are spaced less than about 0.3 mm apart;

a housing having a surface that defines a storage region adapted to store an active substance; and

a power source, which is adapted to apply electrical energy between the two electrodes applied to the skin to cause ablation of the stratum corneum, so as to facilitate passage of the active substance through the skin.

41. A device according to claim 40, wherein the two electrodes are spaced about 0.01-0.1 mm apart.

42. A device according to claim 40, wherein the power source is adapted to generate alternating current, a frequency thereof being above about 100 Hz.

43. A device according to claim 42, wherein the power source is adapted to generate the alternating current such that the frequency is between about 1 kHz and about 300 kHz.

44. A device according to claim 40, wherein the plurality of electrodes are arranged in an array, wherein a density of the electrodes in the array is determined responsive to a desired transdermal transfer rate of the substance.