Iontophoretic drug delivery systems

• US 7,349,733 B2
• Filed: 11/02/2001
• Issued: 03/25/2008
• Est. Priority Date: 11/02/2001
• Status: Expired due to Fees

• Current Assignee: Microlin LLC
• Original Assignee: Ceramatel Incorporated
• Inventors: Joshi, Ashok V.
• Primary Examiner(s): DeSanto; Matthew F.
• Application Number:
  US10/003,853
• Publication Number:
  US 20030088204A1
• Time in Patent Office: 2,335 Days
• Field of Search: 604/20, 604/501, 604/21, 604/22, 604/500, 604/19, 604/890.1, 604/891.1, 604/892.1, 600/377
• US Class Current: 604/20
• CPC Class Codes: A61N 1/0428 Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body

Abstract

An electrotransport device is provided for the site specific delivery of drugs or other beneficial agents across or under a skin or tissue surface. In one embodiment, the electrotransport device is configured in whole, or in part, to be implanted under a subject'"'"'s stratum corneum, and uses an electrical current to facilitate drug or other beneficial agent delivery through a semipermeable membrane and into the tissue of the subject. In another embodiment, a device for intraocular delivery of drug or beneficial agent is disclosed which device is placed on the conjunctiva of a subject, wherein lacrimal fluid completes a circuit for delivering the drug or beneficial agent. Methods of using the devices of the present invention are also provided.

Claims

1. An implantable electrotransport comprising:

a first electrode comprising an electropositive material in operable communication with an ionic fluid;

a second electrode comprising an electronegative material in operable communication with said ionic fluid;

a bio-compatibile semipermeable membrane disposed adjacently under at least a portion of either said first electrode or said second electrode, said semipermeable membrane configured to be in fluid communication with said ionic fluid in an environment in which said electrotransport device is placed;

a compartment adapted for containing a beneficial agent therein, the compartment in operable communication with said first or second electrode, said semipermeable membrane configured to be in fluid communication with any beneficial agent contained in said compartment; and

a conductor, insulated from said ionic fluid, said conductor extending from said first electrode to said second electrode and providing an electrical interconnection therebetween;

wherein said electropositive material, said electronegative conductor and said ionic fluid complete a circuit capable of creating a current beneath a stratum corneum skin layer sufficient to transport said beneficial agent through said membrane without an additional power source.

2. The electrotransport device of claim 1, wherein said compartment has portions formed of a refractory transition metal configured as an electrode housing, said portions coated with a biocompatible material.

3. The electrotransport device of claim 2, wherein said electrode housing is formed of the same refractory transition metal as the first electrode.

4. The electrotransport device of claim 2, wherein said portions are formed of a metal selected from the group consisting of titanium and tantalum.

5. The electrotransport device of claim 1, further comprising a power source in electrical communication with said first electrode.

6. The electrotransport device of claim 5, further comprising a control circuit interposed in said electrical connection between said power source and said first electrode.

7. The electrotransport device of claim 1, wherein said semipermeable membrane is configured to allow flow of molecules from said compartment to the ionic fluid responsive to an electric current delivered thereupon.

8. The electrotransport device of claim 1, wherein said semipermeable membrane is configured to substantially inhibit transport of the molecules therethrough in the absence of an electric current delivered to one of the molecules and said semipermeable membrane.

9. The electrotransport device of claim 1, further comprising a second semipermeable membrane disposed adjacently under said second electrode.

10. The electrotransport device of claim 1, wherein said semipermeable membrane is configured to conduct charged species from said first electrode when implanted under a subject'"'"'s skin surface in whom the electrotransport device has been implanted.

11. The electrotransport device of claim 1, wherein said at least one semipermeable membrane is configured to be substantially microporous throughout, and adapted to substantially prevent blood intrusion into said semipermeable membrane.

12. The electrotransport device of claim 1, wherein said semipermeable membrane is configured to selectively allow the flow of ionized molecules therethrough.

13. The electrotransport device or claim 1, wherein said first electrode is configured as one of a solid, a suspension, a gel, and a solution.

14. The electrotransport devise of claim 1, wherein said second electrode is configured as one of a solid, a suspension, a gel, and a solution.

15. The electrotransport device of claim 1, wherein said first electrode and said beneficial agent are substantially interspersed throughout at least a portion of said compartment.

16. The electrotransport device of claim 1, further comprising a second semipermeable membrane disposed adjacently under at least a portion of second electrode, said second semipermeable membrane configured to be in fluid communication with a second beneficial agent contained in said second electrode, said second semipermeable membrane adapted to be implanted under at least a portion of a subject'"'"'s stratum corneum in whom the electrotransport device has been implanted.

17. The electrotransport device of claim 1, wherein said first ad second electrode are configured as part of a unitary housing.

18. The electrotransport device of claim 1, wherein at least a portion of said semipermeable membrane comprises a material configured to be resorbable by a subject'"'"'s body tissues in whom the electrotransport device has been implanted.

19. An electrotransport device for delivering molecules of a beneficial agent to tissue of a subject upon implantation, said electrotransport device comprising:

a plurality of spaced apart electrodes, each of said plurality of spaced apart electrodes adapted to be placed over a subject'"'"'s tissue surface;

wherein at least one of said plurality of spaced apart electrodes comprises an electropositive or an electronegative material;

at least one insulated conductor extending between two of said plurality of spaced apart electrodes;

at least one reservoir disposed under an electrically conducting area of a first electrode of said plurality of spaced apart electrodes, said at least one reservoir adapted to accommodate the molecules of beneficial agent; and

a bio-compatible ion exchange membrane configured to conduct a current disposed adjacently under said at least one reservoir, said ion exchange membrane adapted to be implanted under at least a portion of the tissue of a subject;

wherein a subject'"'"'s stratum corneum tissue completes a circuit between said plurality of spaced apart electrodes upon implantation under the subject'"'"'s skin surface and enables delivery of molecules of the beneficial agent to the subject.

20. The electrotransport devise of claim 19, wherein a pair of said electrodes are positioned a fixed distance from each other.

21. The electrotransport device of claim 19, wherein said semipermeable membrane is configured to allow the flow of the molecules therethrough responsive to delivery of an electric current thereupon.

22. The electrotransport device of claim 19, wherein said semipermeable membrane is configured to substantially inhibit transport or the molecules in the absence of an electric current delivered to one of the molecules and said semipermeable membrane.

23. The electrotransport device of claim 19, wherein said semipermeable membrane is configured to substantially inhibit transport of the molecules in the absence of an electric current.

24. The electrotransport device of claim 19, wherein said semipermeable membrane is configured to selectively allow the flow of ionized molecules therethrough.

25. The electrotransport device of claim 19, wherein at least part of said semipermeable membrane comprises a material configured to be resorbable by the subject'"'"'s body tissues.

26. The electrotransport device of claim 19, further comprising a second semipermeable membrane disposed in current conducting relationship under a second electrode of said plurality of mutually spaced apart electrodes, said second semipermeable membrane adapted to be implanted under at least a portion of the subject'"'"'s stratum corneum.

27. The electrotransport device of claim 19, further comprising a power source in electrical communication with said plurality spaced apart electrodes.

28. A method of electrically facilitating the transport of a beneficial agent to a body tissue of a subject, said method comprising:

providing a plurality of electrodes configured to conduct electrical current in relation to said body tissue, a first electrode comprising electropositive material and a second electrode comprising electronegative material, said first and second electrodes configured on a single housing;

providing at least one beneficial agent reservoir disposed adjacently to an electrically conductive area of at least one said plurality of electrodes;

including a beneficial agent in said beneficial agent reservoir,

providing at least one semipermeable membrane in fluid communication with said at least one beneficial agent reservoir, said at least one semipermeable membrane configured to substantially inhibit passive diffusion of a beneficial agent therethrough in the absence of an electrical current applied at said at least one semipermeable membrane and said beneficial agent;

implanting at least a portion of said at least one semipermeable membrane beneath a subject'"'"'s stratum corneum skin layer, wherein, responsive to said implanting, a circuit is completed between said plurality of electrodes capable of transmitting a voltage from said plurality of electrodes and said at least one semipermeable membrane to said body tissues beneath said stratum corneum skin layer, said voltage effecting transport of said beneficial agent through said at least one semipermeable membrane, said voltage facilitating transport of said beneficial agent through said body tissue, and

delivering said beneficial agent to the subject'"'"'s body tissues.

29. The method according to claim 28, further comprising implanting the electrodes and the membrane in their entirety beneath the subject'"'"'s stratum corneum skin layer.

30. The method according to claim 28, wherein said providing at least one semipermeable membrane comprises providing at least one semipermeable membrane configured as one of a cationic exchange membrane and an ionic exchange membrane.

31. The method according to claim 28, wherein delivering said beneficial agent to the subject comprises diffusing said beneficial agent through micropores of said at least one semipermeable membrane.

32. The method according to claim 28, wherein said at least one semipermeable membrane is configured to have a molecular cutoff adapted to substantially prevent blood intrusion into said at least one semipermeable membrane.

33. The method according to claim 28, wherein delivering said beneficial agent to said subject comprises electrostatically repelling said beneficial agent trough said at least one semipermeable membrane.

34. The method according to claim 28, further comprising implanting said electrodes and said beneficial agent reservoir under a skin surface of said subject.

35. The method according to claim 28, wherein said implanting at least a portion of said at least one semipermeable membrane beneath a stratum corneum skin layer comprises implanting a bottom-most surface of said at least one semipermeable membrane to a depth approximating about 20-100 μ

m below the stratum skin layer.

36. An intraocular delivery device for delivering a beneficial agent to a subject'"'"'s eye using liquid present on the surface of the subject'"'"'s conjunctiva to complete a circuit between two complementary electrodes configured within said intraocular drug delivery device, said intraocular drug delivery device comprising:

a membrane comprising a polymer, semipermeable to water, and further comprising first and second surfaces, said first surface being adapted to be placed on the subject'"'"'s conjunctiva to interact with any liquid present thereon, said second surface configured to contain a beneficial agent for delivery to the subject;

a first electrode in fluid communication with said membrane and said beneficial agent, said first electrode comprising an electropositive or an electronegative material; and

a second electrode comprising an electropositive or an electronegative material, said second electrode configured to be in fluid communication with the subject'"'"'s conjunctiva, but, except for conductive material connecting said first and second electrodes, electrically isolated from said first electrode, said first and second electrodes being selected, when configured together as a circuit, to form a battery, said first and second electrodes configured on a unitary housing;

wherein, when said intraocular drug delivery device is placed on the subject'"'"'s conjunctiva, any electrically conductive liquid present thereon completes an ionic circuit between said first and second electrodes;

wherein said electropositive or electronegative material of said first electrode is complementary to said second electronegative or electropositive material of said second electrode, respectively, such that when electrically connected with any electrically conductive liquid present on the subject'"'"'s conjunctiva, said battery is formed that drives the beneficial agent through said membrane for delivery to the subject'"'"'s conjunctiva upon completing an electronic circuit.

37. The intraocular delivery device of claim 36, wherein the electropositive or electronegative material of the first electrode is magnesium.

38. The intraocular device of claim 36, wherein the electropositive or electronegative material of the second electrode is carbon.