Tissue electroperforation for enhanced drug delivery and diagnostic sampling

• US 20020010414A1
• Filed: 02/28/2001
• Published: 01/24/2002
• Est. Priority Date: 08/25/1999
• Status: Active Grant

• Current Assignee: Cilag Gmbh International (Johnson & Johnson)
• Original Assignee: Johnson & Johnson Consumer Companies Incorporated (Johnson & Johnson)
• Inventors: Wang, Jonas C.T., Sun, Ying, Coston, Anthony F., Oakeson, Ralph W., Wisniewski, Stephen J.
• Granted Patent: US 7,133,717 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61N 1/0428 Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• 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

The present invention relates to a method and a device for transporting a molecule through a mammalian barrier membrane of at least one layer of cells comprising the steps of: ablating said membrane with an electric current from an array of treatment electrodes; and utilizing a driving force to move said molecule through said perforated membrane.

Claims

1. A method for transporting a molecule through a mammalian barrier membrane of at least one layer of cells comprising the steps of:

creating a gap between an array of treatment electrode and said membrane;

ablating said membrane with an electric current from the array of treatment electrodes; and

utilizing a driving force to move said molecule through said perforated membrane.

2. A method of claim 1, wherein said electric current forms an electric arc between said treatment electrode and said membrane.

3. A method of claim 1, wherein said method further comprises the use of an indifferent electrode, where said electric current passes from said treatment electrode to said indifferent electrode.

4. A method of claim 1, wherein said electric current comprises a direct current.

5. A method of claim 1, wherein said electric current comprises an alternating current.

6. A method of claim 1, wherein said electric current has a frequency of between about 60 kHz to about 5,000 kHz.

7. A method as in claim 1, wherein the waveform of said electric current is selected from the group consisting of damped sine wave, modulated sine wave, pure sine wave, damped square wave, modulated square wave, pure square wave, direct current and a blend wave thereof.

8. A method of claim 1, wherein said membrane is selected from the group consisting of skin, buccal, vaginal, and rectal membranes.

9. A method of claim 8, wherein said membrane is the stratum corneum of a human.

10. A method of claim 1, wherein said driving force is selected from a group consisting of iontophoresis, electro-osmosis, reverse iontophoresis, electroperforation, phonophoresis, pressure gradients, heat and concentration gradients.

11. A method of claim 1, wherein said molecule is a pharmaceutical transported through said membrane into said mammal.

12. A method of claim 11, wherein said pharmaceutical is selected from the group consisting of polysaccharides, peptides, proteins, and polynucleotides.

13. A method of claim 1, wherein said molecule in transported from within said mammal out through said membrane.

14. A method of claim 1, further comprising the step of piercing said membrane with a member selected from the group consisting of needles or blades.

15. A method of claim 1, further comprising the step of applying a conductive material to said membrane prior to said ablation.

16. A method of claim 15, wherein said conductive material is selected from the group consisting of electrolytes, metal particles, and carbon particles.

17. A method of claim 1, further comprising the step of cooling said membrane prior to or during said ablation.

18. A method of claim 1, further comprising the step of applying an analgesic to said membrane prior to or during said ablation.

19. A method of claim 1, further comprising the step of monitoring the electrical resistance or impedance of said membrane in order to determine the presence of ablation in said membrane.

20. A device for transporting a molecule through a barrier membrane of a mammal comprising:

a housing having a barrier membrane contacting surface;

a reservoir having a orifice in communication with said skin contacting surface;

a plurality of electrodes wherein each electrode defines an air gap between the barrier membrane and a distal tip of each electrode;

a power supply for providing RF energy to an electronic control circuit, the control circuit comprising;

a modulating circuit for selectively providing RF energy to one or more of the plurality of electrodes

wherein upon contacting said skin contacting surface with said membrane, said device is capable of both ablating said membrane with said electric current and transporting said molecule either from said reservoir, through said membrane, and into said mammal or from said mammal, through said membrane, and into said reservoir.

21. A device of claim 20, wherein said delivered current comprises an alternating current.

23. A device as in claim 20, wherein the waveform of said delivered electric current is selected from the group comprising damped sine wave, modulated sine wave, pure sine wave, damped square wave, modulated square wave, pure square wave, direct current, and a blend wave thereof.

24. A device of claim 20, wherein said device comprises an indifferent electrode.

25. A device of claim 20, said device further comprising a sensor for monitoring the electrical resistance or impedance of said membrane.

26. A device of claim 20, wherein said reservoir comprises an iontophoretic electrode.

22. A device of claim 22, wherein said delivered current has a frequency of between about 60 kHz to about 5,000 kHz.

27. A device of claim 27, wherein said reservoir comprises a delivery electrode and a semipermeable membrane, wherein said semipermeable membrane separates said delivery electrode and said orifice.

28. A device of claim 27, wherein said reservoir further comprises a sensor selected from the group consisting of sensors for measuring the pH, molecule or ion concentration, electric conductivity, amperage, and potential, pressure, color and temperature of fluid in said reservoir.

29. A method for transporting a molecule through a mammalian barrier membrane of at least one layer of cells comprising the steps of:

creating a gap between an array of treatment electrodes and said membrane;

selectively energizing at least one electrode of the array of treatment electrodes with an electric current to ablate the membrane;

sensing the depth of ablation penetration of the membrane;

comparing the sensed depth of ablation penetration with a predetermined threshold; and

utilizing a driving force to move said molecule through said perforated membrane.

30. The method of claim 30 wherein sensing the depth of penetration comprises measuring the impedance of the membrane.