Transdermal drug delivery and analyte extraction

• US 6,148,232 A
• Filed: 11/09/1998
• Issued: 11/14/2000
• Est. Priority Date: 11/09/1998
• Status: Expired due to Term

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: Elecsys Incorporated
• Inventors: Avrahami, Zohar
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US09/189,170
• Time in Patent Office: 736 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 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 a substance through the ablated area during a second time period, subsequent to the first time period.

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 stratum corneum causes a puncturing thereof.

4. 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.

5. A device according to claim 4, wherein the characteristic of the current is drawn from a list consisting of:

the 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.

6. A device according to claim 4, 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.

7. A device according to claim 4, 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.

8. A device according to claim 4, 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.

9. A device according to claim 8, wherein the dissolving element is adapted such that the function comprises a time-integral of the current having passed through the dissolving element.

10. A device according to claim 8, wherein the dissolving element comprises:

an electrolyte solution within the element; and

a first node and a common node immersed in the electrolyte solution,

wherein the dissolving element is adapted so that current flows from the first node to the common node through the electrolyte solution, wherein the common node is adapted to be consumed by the current flow at a rate generally proportional to the current passing therethrough, and wherein the dissolving element is adapted to become substantially nonconductive when the total charge having passed through the common node exceeds a common node threshold value.

11. A device according to claim 10, wherein the dissolving element further comprises a second node, immersed in the electrolyte solution, wherein the power source is adapted to generate alternating current, and wherein the device further comprises:

a first diode, coupled in series between the power source and the first node, which is adapted to conduct current from the power source to the first node when the alternating current is in a positive phase thereof; and

a second diode, coupled in series between the power source and the second node, which is adapted to conduct current from the second node to the power source when the alternating current is in a negative phase thereof,

such that the dissolving element is adapted to become substantially nonconductive when the total charge having passed through the common node exceeds a common node threshold value.

12. A device according to claim 8, wherein the dissolving element comprises:

an electrolyte solution within the element;

a large-area anode immersed in the electrolyte solution; and

a plurality of cathodes, immersed in the electrolyte solution, each of the cathodes being coupled to a respective one of the plurality of electrodes,

wherein the dissolving element is adapted such that current flows from the large-area anode to the plurality of cathodes through the electrolyte solution, wherein at least one of the cathodes is adapted to be consumed by the current flow at a rate generally proportional to the current passing therethrough, and wherein the at least one cathode is adapted to become substantially nonconductive responsive to a function of the current having passed therethrough.

13. A device according to claim 4, 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.

14. A device according to claim 4, 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.

15. A device according to claim 14, wherein the power source comprises a current source, which is adapted to reduce the current responsive to a measurement made by the sensing unit which indicates that the electrical potential between the two electrodes is below a voltage-threshold value.

16. A device according to claim 14, and comprising a resistive element coupled to one of the two electrodes and to the power source, wherein the voltage sensing unit is further coupled to measure a voltage drop across the resistive element in order to determine a current passing therethrough, wherein the power source comprises an alternating current source, such that the measurements of the voltage drop across the two electrodes and the current through the resistive element determine a phase shift, and wherein the alternating current source is adapted to reduce the current through the stratum corneum responsive to the phase shift being below a threshold value.

17. A device according to claim 4, 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 4, 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 therethrough being greater than a threshold value.

19. A device according to claim 4, 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 electrodes comprise:

a common electrode, which has a plurality of perforations therethrough; and

a plurality of positive electrodes, each positive electrode passing through a respective perforation of the common electrode,

wherein the power source is adapted such that current from the power source flows from each positive electrode through the skin to the common electrode.

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

24. A device according to claim 23, wherein the power source is adapted to generate the alternating current such that the frequency is between about 1 kHz and about 300 kHz.

25. 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.

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

27. A device according to claim 26, wherein the power source is adapted to apply the electrical energy for less than about 200 milliseconds.

28. A device for passing electrical current through skin on the body of a subject, comprising:

a power source, which is adapted to generate the current;

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

an electrically conductive dissolving element coupled to at least one of the electrodes, the element being adapted to have a dissolving rate generally proportional to the current passing therethrough, and to become substantially nonconductive responsive to a function of the current passing therethrough.

29. 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, between two or more of the plurality of electrodes, an alternating electric current so as to cause ablation of the stratum corneum.

30. A device according to claim 29, wherein the power source is adapted to apply the alternating current at a frequency above about 100 Hz.

31. A device according to claim 30, wherein the power source is adapted to apply the alternating current at a frequency between about 1 kHz and about 300 kHz.

32. 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 points are spaced less than about 0.3 mm apart; and

a power source, which is adapted to apply electrical energy between the two electrodes applied to the skin at the two points, to cause ablation of the stratum corneum.

33. A device according to claim 32, wherein the two points are spaced about 0.01-0.1 mm apart.

34. A device according to claim 32, wherein the device is adapted to ablate the area of the stratum corneum in order to allow a substance to pass therethrough.

35. A device according to claim 34, wherein the device is adapted to ablate the area of the stratum corneum so as to allow the substance to pass through the skin into the body of the subject.

36. A device according to claim 34, wherein the device is adapted to ablate the area of the stratum corneum so as to allow the substance to pass through the skin from within the body.