Transdermal drug delivery and analyte extraction

• US 6,615,079 B1
• Filed: 08/10/2000
• Issued: 09/02/2003
• 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:
  US09/635,892
• Time in Patent Office: 1,118 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 method for ablating stratum corneum epidermidis of a subject, comprising:

applying electrical energy between points on the skin, so as to cause ablation of an area of the stratum corneum during a first time period; and

applying a drug to the ablated area during a second time period, subsequent to the first time period, so that passage of the drug through the stratum corneum is facilitated by the ablation.

2. A method according to claim 1, wherein applying the electrical energy comprises applying the energy for less than about 1 second.

3. A method according to claim 2, wherein applying the electrical energy comprises applying the energy for less than about 200 milliseconds.

4. A method for ablating stratum corneum epidermidis of a subject, comprising:

applying electrical energy between points on the skin, so as to cause ablation of an area of the stratum corneum during a first time period; and

extracting an analyte through the ablated area during a second time period, subsequent to the first time period, so that passage of the analyte through the stratum corneum is facilitated by the ablation.

5. A method according to claim 4, wherein applying the electrical energy comprises applying the energy for less than about 1 second.

6. A method according to claim 5, wherein applying the electrical energy comprises applying the energy for less than about 200 milliseconds.

7. A method for passing electrical current through the skin of a subject, comprising:

placing a plurality of electrodes against the skin at respective points;

applying the current through the electrodes; and

coupling to at least one of the electrodes an electrically conductive dissolving element, the element being characterized by having a dissolving rate generally proportional to the current passing therethrough, and by becoming substantially nonconductive responsive to a function of the current passing therethrough.

8. A method for ablating stratum corneum epidermidis of skin of a subject, comprising applying electrical energy to the skin of the subject between points on the skin which are spaced less than 0.3 mm apart, so as to cause ablation of the stratum corneum.

9. A method according to claim 8, wherein applying the energy between the two points comprises applying the energy between points on the skin which are spaced about 001-0.1 mm apart.

10. A method for ablating the stratum corneum epidermidis of a subject, comprising:

placing a plurality of electrodes against the subject'"'"'s skin at respective points; and

applying 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.

11. A method according to claim 10, wherein placing the plurality of the electrodes comprises placing at least one set of two or more electrodes against the skin, and wherein applying the electrical energy comprises inducing the current to flow between the electrodes in the at least one set.

12. A method according to claim 10, wherein placing the plurality of the electrodes comprises placing a common electrode and a plurality of individual electrodes against the skin, and wherein applying the electrical energy comprises inducing the current to flow between the plurality of individual electrodes and the common electrode.

13. A method according to claim 10, wherein applying the energy comprises ablating the area of the stratum corneum in order to allow a substance to pass through the area.

14. A method according to claim 13, wherein placing the plurality of electrodes comprises placing an array of the electrodes against the skin, wherein a density of the electrodes in the array is determined responsive to a desired transdermal transfer rate of the substance.

15. A method according to claim 13, and comprising delivering a drug through the area.

16. A method according to claim 13, and comprising extracting an analyte through the area.

17. A method according to claim 10, wherein skin layers beneath the stratum corneum are substantially not ablated.

18. A method according to claim 10, wherein applying the electrical energy comprises puncturing the skin.

19. A method according to claim 10, wherein applying electrical energy comprises:

causing a current to flow through the points on the skin; and

substantially reducing the current flow through the skin responsive to variation of a characteristic of the current.

20. A method according to claim 19, wherein the characteristic 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.

21. A method according to claim 19, wherein causing the current to flow comprises passing current to the one or more points on the skin through one or more respective limited-conduction units, wherein the units allow current below a threshold value to flow therethrough substantially unimpeded, and wherein the units become substantially nonconductive if the current flowing therethrough exceeds a limited-conduction threshold value.

22. A method according to claim 19, wherein causing the current to flow comprises passing current to the one or more points on the skin through one or more respective electrically conductive dissolving elements, each element characterized by a dissolving rate generally proportional to the current passing therethrough, and becoming substantially nonconductive when the total charge having passed therethrough exceeds a dissolving element threshold value.

23. A method according to claim 19, wherein reducing the current flow comprises reducing the current at one of the respective points substantially independently of the current at another one of the respective points.

24. A method according to claim 19, wherein reducing current flow comprises:

monitoring the current flow through one of the plurality of electrodes; and

reducing the current flow through another one of the plurality of electrodes responsive thereto.

25. A method according to claim 10, wherein applying electrical energy comprises generating alternating current, a frequency thereof being above about 100 Hz.

26. A method according to claim 25, wherein the frequency is between about 1 kHz and about 300 kHz.

27. A method according to claim 10, wherein applying electrical energy comprises generating alternating current and modulating a frequency thereof between a first frequency value and a second frequency value.

28. A method according to claim 10, wherein placing the plurality of electrodes comprises placing two of the plurality of electrodes at a separation therebetween that is less than about 0.3 mm.

29. A method according to claim 28, wherein placing the plurality of electrodes comprises placing the two of the plurality of electrodes at a separation between about 0.01 mm and about 0.1 mm.

30. A method according to claim 10, wherein placing the plurality of electrodes comprises:

applying a conduction-enhancing material to an area on the surface of the subject'"'"'s skin in order to enhance current flow through the skin; and

placing the electrodes on the material,

wherein the electrical resistance of the conduction-enhancing material increases responsive to a function of the current flow therethrough.

31. A method according to claim 10, wherein placing the plurality of electrodes comprises:

placing on the skin a common electrode which has a plurality of perforations therethrough; and

placing on the skin a plurality of positive electrodes, each positive electrode passing through a respective perforation in the common electrode,

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

32. A method according to claim 10, and comprising positioning in a vicinity of the electrodes a medical patch containing the substance, such that ablation of the stratum corneum increases a transport rate of the substance from the patch into the skin.