Electroporation device for in vivo delivery of therapeutic agents

• US 6,775,569 B2
• Filed: 11/05/1997
• Issued: 08/10/2004
• Est. Priority Date: 11/05/1997
• Status: Expired due to Fees

• Current Assignee: Hisamitsu Pharmaceutical Company Incorporated
• Original Assignee: Hisamitsu Pharmaceutical Company Incorporated
• Inventors: Mori, Kenji, Nozawa, Iwao, Sato, Shuji
• Primary Examiner(s): Thanh, Loan H.
• Application Number:
  US08/964,872
• Publication Number:
  US 20010039393A1
• Time in Patent Office: 2,470 Days
• Field of Search: 604/20-22, 604/501, 604/103.01, 604/103.02, 435/173.6, 607/148, 607/152, 607/153
• US Class Current: 604/20
• CPC Class Codes: A61N 1/042 Material of the electrode
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

Electroporation electrodes are laminated to a permeable membrane to form an electrode membrane. Such an electrode membrane is useful for a continuous controlled delivery of a therapeutic agent through the skin or mucosa, when placed in direct contact with the skin or mucosa and by application of electric field pulses at specified intervals. An electrode membrane can be assembled such that it incorporates an iontophoretic electrode in the same device. This device can be jointly utilized for electroporation and iontophoretic drug delivery through the skin and mucosal membrane.

Claims

1. An external electroporation device for administering a therapeutic agent, comprising

an electrode membrane, the electrode membrane comprising

a pair of contact electrodes fixed on, protruding from, or entirely embedded within an agent permeable membrane;

a casing attached to the electrode membrane; and

a reservoir formed between the casing and the electrode membrane, such that when the external electroporation device contacts a site of administration, the pair of contact electrodes directly contact the site of administration.

2. The device of claim 1 where the agent permeable membrane has pores with a diameter from about 0.01 μ

m to 10 μ

m.

3. The device of claim 2 where the agent permeable membrane has pores with a diameter from about 0.1 μ

m to 5 μ

m.

4. The device of claim 1 where the agent permeable membrane is made from at least one material which has a permeability matched to permeation characteristics of the therapeutic agent.

5. The device of claim 1, wherein the agent permeable membrane is selected from the group consisting of:

nylon, polyvinylidene flouride, cellulose, nitro cellulose, polycarbonate, polysulfone, polyethylene, polypropylene, nonwoven fabric, gauze, woven fabric, paper, cotton, polyethylene foam, polypropylene foam, polyvinyl actetate foam, polyorefine foam, polyamide foam, polyurethane foam and combinations thereof.

6. The device of claim 1 where the contact electrodes are from about 10 μ

m to 1 cm apart.

7. The device of claim 6 where the contact electrodes are from about 50 μ

m to 5 mm apart.

8. The device of claim 7 where the contact electrodes are from about 100 μ

m to 2 mm apart.

9. The device of claim 1 where the contact electrodes are made from a metal or a semiconductor.

10. The device of claim 1 where the contact electrodes are made from carbon, silver, or silver chloride.

11. The device of claim 1 which is adapted for application to skin or mucosa.

12. The device of claim 1 where the casing is made from a material that is elastically deformable.

13. The device of claim 1 where the casing is made from a material that is water-resistant.

14. The device of claim 1 where the casing is made from a polymer or copolymer.

15. The device of claim 1 where the casing is made from at least one material selected from the group consisting of:

polyvinylidene chloride, polyvinyl chloride, polyorefine, polyester, polystyrene, poly acryl, polyamide, polyoxymethylene, polyphenylenesulfuramide, polyamide, polyimide, polyacrylonitrile, polyetherketone, polyethersulfone, polysulfone, etherimide, polybutadiene, and isoprene.

16. The device of claim 1 where the casing is from about 5 to 250 μ

m thick.

17. The device of claim 1 which further includes a pharmaceutical composition having a therapeutic agent where the pharmaceutical composition is contained in the reservoir.

18. The device of claim 17 where the pharmaceutical composition further includes one or more substances selected from the group consisting of:

an electrolyte, an absorption accelerant, a stabilizer, a pH buffer, a thickener, a detergent, an emulsifier, an ion exchange resin, an ion exchange membrane, a nonwoven fabric and combinations thereof.

19. The device of claim 1 where the reservoir includes an iontophoretic electrode.

20. The device of claim 19 where the iontophoretic electrode is a polarized electrode made from a material selected from the group consisting of:

carbon, platinum, gold, or titanium.

21. The device of claim 19 where the iontophoretic electrode is an unpolarized electrode.

22. The device of claim 21 where the iontophoretic electrode is an anode electrode which includes copper.

23. The device of claim 21 where the iontophoretic electrode is an anode electrode which includes silver.

24. The device of claim 21 where the iontophoretic electrode is a cathode electrode which includes copper chloride.

25. The device of claim 21 where the iontophoretic electrode is a cathode electrode which includes silver chloride.

26. The device of claim 1 where the therapeutic agent is one or more agents selected from the group consisting of:

an analgesic, a peptide/protein, a tranquilizer, an antineoplastic drug, a cardiotonic, a hormone, a hypotensive drug, and a polynucleotide.

27. The device of claim 1 which further includes an adhesion layer upon the electrode membrane which contacts the site of administration.

28. The device of claim 1 where the casing is sealed to the electrode membrane using heat sealing.

29. The device of claim 17 where the therapeutic agent is one or more agents selected from the group consisting of:

an analgesic, a peptide/protein, a tranquilizer, an antineoplastic drug, a cardiotonic, a hormone, a hypotensive drug, and a polynucleotide.

30. The device of claim 1 which further includes an adhesion layer upon the electrode membrane which contacts the site of administration.