Method for electrokinetic delivery of medicaments

• US RE38,341 E1
• Filed: 12/27/1999
• Issued: 12/09/2003
• Est. Priority Date: 05/08/1996
• Status: Expired due to Term

• Current Assignee: Nitric Biotherapeutics, Inc.
• Original Assignee: Biophoretic Therapeutic Systems, LLC
• Inventors: Henley, Julian L.
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US09/472,524
• Time in Patent Office: 1,443 Days
• Field of Search: 604/19, 604/20, 604/289, 604/501, 607/3, 607/113, 607/133-145
• 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

Abstract

A portable iontophoresis apparatus for facilitating delivery of medication across the cutaneous membrane into adjacent underlying tissues and blood vessels. The apparatus employs a modular, detachable non-reusable medicament-containing applicator electrode which is adapted to attach to a base assembly. The apparatus is designed to be hand-held and includes a circumferential tactile electrode band on the base assembly which provides electrical connection between the skin of the user'"'"'s hand and one pole of a bipolar power source housed within the base assembly. The opposing pole of the power source is connected to the applicator electrode. The user'"'"'s body completes the electrical circuit between the applicator and tactile electrodes. A method for using the device for the treatment of Herpes simplex infection and related viral infections which produce similar cutaneous lesions is presented. The apparatus, when used in accordance with the method described herein, demonstrated >90% treatment efficacy in clinical trials.

Claims

1. A method for treating mucocutaneous Herpes Type I and Type II infections present mucocutaneous lesion comprising the iontophoretic transdermal delivery of a [2-hydroxyethoxy(methyl)]guanine into tissue overlying said lesion.

2. A method for treating Herpes conditions in accordance with claim 1 for clinical conditions suspected to be caused by Herpes Simplex virus infection.

3. A method for treating lesions associated with cold sores and genital herpes comprising the dispensation, application and transdermal self-application of an active antiviral agent contained within a hand-held iontophoretic device to said lesions wherein said antiviral agent is 5-iodo-2-deoxyuridine or derivatives thereof.

4. A method of treating Herpes Type I and Type II infection in an individual by self-administration of an anti-viral agent, the method comprising the steps of:

(a) providing a portable hand-held electrokinetic device having an applicator electrode in electrical communication with a self-contained electrical power source housed within the device, said applicator electrode including an electrokinetically transportable anti-viral agent comprising 9-[2-hydroxyethoxy(methyl)]guanine effective for treating Herpes Type I and Type II infection, a contact surface, and a substrate having a reservoir containing said anti-viral agent;

(b) rupturing the reservoir to supply the anti-viral agent to the substrate;

(c) while holding the device, manipulating the device to place the contact surface of the applicator electrode into overlying relation with an individual'"'"'s infection site with the anti-viral agent in the substrate interposed between said applicator electrode and the infection site enabling electrical contact between the applicator electrode and the infection site;

(d) applying from said electrical power source a voltage gradient between the applicator electrode and the infection site to establish electrical contact therebetween by completing an electrical circuit with said power source through the individual'"'"'s hand holding the device, the infection site, the anti-viral agent and the applicator electrode, whereby said anti-viral agent is electrokinetically motivated from the substrate into the infection site; and

(e) while holding the device in overlying relation with the infection site, providing the electrical contact between the applicator electrode and the infection site until a therapeutically effective dose of said anti-viral agent has been electrokinetically transported into said infection site.

5. The method of claim 4 including, after use, removing the applicator electrode from the device and replacing the used applicator electrode on the device with a replacement applicator electrode.

6. The method of claim 4, including preventing reuse of the applicator electrode after a one-time use thereof.

7. The method of claim 4 including indicating usage of the applicator electrode.

8. The method of claim 4 including providing a tactile electrode on said device for contact by the individual'"'"'s hand holding the device, said tactile electrode being in electrical contact with said power source, the step of completing the electrical circuit including contacting the device with a portion of the individual'"'"'s hand to provide electrical contact between the tactile electrode and the individual'"'"'s hand holding the device.

9. A method according to claim 4 including providing a voltage multiplier within said device in electrical contact with said power source for stepping up the voltage supplied said applicator electrode.

10. A method according to claim 9 including providing a current driver within said device in electrical contact with said voltage multiplier and said applicator electrode for presenting a voltage output sufficient to maintain a defined current at said applicator electrode and incrementally increasing the level of the current at the start of the treatment to a predetermined controlled current level.

11. A method according to claim 4 including providing said hand-held device with a prepackaged unit dose of said anti-viral agent.

12. A method according to claim 4 wherein the method includes treating clinical conditions suspected to be caused by Herpes Simplex virus infection.

13. A method according to claim 4 including forming said rupturable reservoir of a material inert to said anti-viral agent.

14. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual comprising the steps of:

(a) providing a portable hand-held electrokinetic device having an applicator electrode and a ground electrode in electrical communication with a self-contained electrical power source housed within the device, said applicator electrode including a prepackaged unit dose of an electrokinetically transportable medicament, a reservoir containing the medicament, a contact surface and a substrate;

(b) rupturing the reservoir to supply the medicament to the substrate;

(c) placing the contact surface of the applicator electrode into electrical contact with the individual'"'"'s treatment site and placing the ground electrode into electrical contact with another site on the individual'"'"'s body;

(d) causing electrical current to flow through said applicator electrode, the medicament in the substrate interposed between the applicator electrode and the treatment site, the treatment site, and the ground electrode by way of the individual'"'"'s treatment site and said another site for electrokinetically motivating said medicament from the substrate into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source; and

(e) maintaining said electrical current flow until a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site.

15. A method according to claim 14 wherein said prepackaged unit dose of said medicament comprises 5-iodo-2-deoxyuridine.

16. A method according to claim 14 wherein said prepackaged unit dose of said medicament comprises 9-[2-hydroxyethoxy(methyl)]guanine.

17. A method according to claim 14 including providing a tactile electrode on said device for contact by a portion of the individual'"'"'s hand holding the device and in electrical contact with said power source, the step of completing the electrical circuit including grasping the device to provide electrical contact between the tactile electrode and the portion of the individual'"'"'s hand holding the device.

18. A method according to claim 14, including, after use, removing the applicator electrode from the handpiece and replacing the used applicator electrode on the device with a replacement applicator electrode.

19. A method according to claim 14, including preventing reuse of the applicator electrode after a one-time use thereof.

20. A method according to claim 14 including maintaining an electrical current output level at the applicator electrode between 0.1 and 5 milliampere per square centimeter of said applicator electrode.

21. A method according to claim 14 including maintaining an electrical current output level at the applicator electrode between 0.1 and 1.2 milliampere per square centimeter of said applicator electrode.

22. A method according to claim 14 including incrementally increasing the level of current at the start of the treatment to a predetermined controlled current level.

23. A method according to claim 14 including incrementally increasing the level of current at the start of the treatment to a predetermined controlled current level and gradually terminating the electrical current to the electrode at the end of the treatment.

24. A method according to claim 14 wherein said medicament comprises an anesthetic.

25. A method according to claim 24 wherein said anesthetic comprises xylocaine.

26. A method according to claim 14 including applying steps (a)-(e) for treating clinical conditions suspected to be caused by Herpes Simplex virus infection.

27. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual comprising the steps of:

(a) providing a portable hand-held electrokinetic device having an applicator electrode and a ground electrode in electrical communication with a self-contained electrical power source housed within the device, said applicator electrode including an electrokinetically transportable medicament and a contact surface;

(b) placing the contact surface of the applicator electrode into electrical contact with the individual'"'"'s treatment site and placing the ground electrode into electrical contact with another site on the individual'"'"'s body;

(c) causing electrical current to flow through said applicator electrode, the medicament interposed between the applicator electrode and the treatment site, the treatment site, and the ground electrode by way of the individual'"'"'s treatment site and said another site for electrokinetically motivating said medicament into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source;

(d) maintaining said electrical current flow until a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site; and

(e) providing said applicator electrode with a substrate comprising a porous matrix and a rupturable reservoir formed of a material inert to said medicament and containing a unit dose of said medicament, and, after rupturing the reservoir, electrokinetically driving the medicament through the porous substrate into the individual'"'"'s treatment site.

28. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual comprising the steps of:

(a) providing a portable hand-held electrokinetic device having an applicator electrode and a ground electrode in electrical communication with a self-contained electrical power source housed within the device, said applicator electrode including an electrokinetically transportable medicament and a contact surface;

(b) placing the contact surface of the applicator electrode into electrical contact with the individual'"'"'s treatment site and placing the ground electrode into electrical contact with another site on the individual'"'"'s body;

(c) causing electrical current to flow through said applicator electrode, the medicament interposed between the applicator electrode and the treatment site, the treatment site, and the ground electrode by way of the individual'"'"'s treatment site and said another site for electrokinetically motivating said medicament into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source;

(d) maintaining said electrical current flow until a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site; and

(e) preventing reuse of the applicator electrode after a one-time use thereof.

29. A method according to claim 28, wherein said medicament comprises 5-iodo-2-deoxyuridine or derivatives thereof.

30. A method according to claim 28 wherein said medicament comprises 9-[hydroxyethoxy(methyl)]guanine.

31. A method according to claim 28 wherein said medicament comprises an anesthetic.

32. A method according to claim 28 wherein said anesthetic comprises xylocaine.

33. A method according to claim 28 including providing a tactile electrode on said device for contact by a portion of the individual'"'"'s hand holding the device and in electrical contact with said power source, the step of completing the electrical circuit including grasping the device to provide electrical contact between the tactile electrode and the portion of the individual'"'"'s hand holding the device.

34. A method according to claim 28, including, after use, removing the applicator electrode from the handpiece and replacing the used applicator electrode on the device with a replacement applicator electrode.

35. A method according to claim 28 wherein said applicator electrode includes a substrate and a reservoir containing the medicament and including the step of rupturing the reservoir to supply medicament to the substrate and from the substrate through the contact surface into the individual'"'"'s treatment site.

36. A method according to claim 35 wherein said substrate comprises a porous matrix and including forming said rupturable reservoir of a material inert to said medicament and, after rupturing the reservoir, electrokinetically driving the medicament through the porous substrate into the individual'"'"'s treatment site.

37. A method according to claim 28 including maintaining an electrical current output level at the applicator electrode between 0.1 to 5 milliampere per square centimeter of said applicator electrode.

38. A method according to claim 28 including maintaining an electrical current output level at the applicator electrode between 0.1 and 1.2 milliampere per square centimeter of said applicator electrode.

39. A method according to claim 28 including incrementally increasing the level of current at the start of the treatment to a predetermined controlled current level.

40. A method according to claim 28 including incrementally increasing the level of current at the start of the treatment to a predetermined controlled current level and gradually terminating the electrical current to the electrode at the end of the treatment.

41. A method according to claim 28 for treating clinical conditions suspected to be caused by Herpes Simplex virus infection.

42. A method according to claim 28 including providing the applicator electrode with a prepackaged unit dose of medicament, and releasing the unit dose of medicament for electrokinetic transport through the contact surface of the applicator electrode into the treatment site.

43. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual comprising the steps of:

(a) providing a portable hand-held electrokinetic device having an applicator electrode and a ground electrode in electrical communication with a self-contained electrical power source housed within the device;

(b) providing a voltage multiplier within said device in electrical contact with said power source and said applicator electrode for stepping up the voltage supplied said applicator electrode and providing a current driver within said device in electrical contact with said voltage multiplier and said applicator electrode for presenting a voltage output sufficient to maintain a defined current at said applicator electrode;

(c) locating the ground electrode on said device for contact by an individual'"'"'s hand holding the device whereby the ground electrode serves as a tactile electrode;

(d) providing said applicator electrode with a prepackaged unit dose of an electrokinetically transportable medicament and a contact surface;

(e) while holding the device with the individual'"'"'s hand in contact with the tactile electrode, placing the contact surface of the applicator electrode into electrical contact with the individual'"'"'s treatment site;

(f) causing electrical current to flow through said applicator electrode, medicament interposed between the applicator electrode and the treatment site, the treatment site, and the tactile electrode by way of the individual'"'"'s treatment site and the individual'"'"'s hand holding the device in contact with the tactile electrode for electrokinetically motivating said medicament into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source; and

(g) maintaining electrical current flow until the unit dose of medicament is at least partially depleted and a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site, said applicator electrode including a substrate comprised of a porous matrix and a reservoir containing the prepackaged unit dose of medicament and inert to the medicament, including the step of rupturing the reservoir to supply medicament to the substrate and electrokinetically drive the medicament from the substrate through the contact surface into the individual'"'"'s treatment site.

44. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual, comprising the steps of:

(a) providing a portable electrokinetic device having a single one-time usage applicator electrode and a ground electrode in electrical communication with a self-contained power source housed within the device;

(b) providing a voltage multiplier within said device in electrical contact with said power source and said applicator electrode for stepping up the voltage supplied said applicator electrode and providing a current driver within said device in electrical contact with said voltage multiplier and said applicator electrode for presenting a voltage output sufficient to maintain a defined current at said applicator electrode;

(c) providing said applicator electrode with a prepackaged unit dose of an electrokinetically transportable medicament and a contact surface, said applicator electrode including a substrate having a reservoir containing said prepackaged unit dose of the medicament;

(d) rupturing the reservoir to supply the medicament to the substrate;

(e) locating the ground electrode on said device for contact by a portion of an individual'"'"'s body whereby the ground electrode serves as a tactile electrode;

(f) placing the contact surface of the applicator electrode into electrical contact with the individual'"'"'s treatment site;

(g) while maintaining the ground electrode in electrical contact with the individual'"'"'s body portion and the contact surface of the applicator electrode in electrical contact with the individual'"'"'s treatment site, causing electrical current to flow through said applicator electrode, the medicament interposed between the applicator electrode and the treatment site, the treatment site, and the tactile electrode by way of the individual'"'"'s treatment site and the individual'"'"'s body portion for electrokinetically motivating said medicament from the substrate into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source; and

(h) maintaining electrical current flow until the unit dose of medicament is at least partially depleted and a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site.

45. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual, comprising the steps of:

(a) providing a portable electrokinetic device having applicator electrode and a ground electrode in electrical communication with a self-contained electrical power source housed within the device;

(b) providing a voltage multiplier within said device in electrical contact with said power source and said applicator electrode for stepping up the voltage supplied said applicator electrode and providing a current driver within said device in electrical contact with said voltage multiplier and said applicator electrode for presenting a voltage output sufficient to maintain a defined current at said applicator electrode;

(c) providing said applicator electrode with a prepackaged unit dose of an electrokinetically transportable medicament and a contact surface;

(d) locating the ground electrode on said device for contact by a portion of an individual'"'"'s body whereby the ground electrode serves as a tactile electrode;

(e) placing the contact surface of the applicator electrode into electrical contact with the individual'"'"'s treatment site;

(f) while maintaining the ground electrode in electrical contact with the individual'"'"'s body portion and the contact surface of the applicator electrode in electrical contact with the individual'"'"'s treatment site, causing electrical current to flow through said applicator electrode, the medicament interposed between the applicator electrode and the treatment site, the treatment site, and the tactile electrode by way of the individual'"'"'s treatment site and the individual'"'"'s body portion for electrokinetically motivating said medicament into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source; and

(g) maintaining electrical current flow until the unit dose of medicament is at least partially depleted and a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site, said substrate comprising a porous matrix and a rupturable reservoir of a material inert to said medicament and including the step of rupturing the reservoir to supply medicament to the substrate, and, after rupturing the reservoir, electrokinetically driving the medicament through the porous substrate into the individual'"'"'s treatment site.

46. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual, comprising the steps of:

(a) providing a portable electrokinetic device having an applicator electrode and a ground electrode in electrical communication with a self-contained electrical power source housed within the device;

(b) providing a voltage multiplier within said device in electrical contact with said power source and said applicator electrode for stepping up the voltage supplied said applicator electrode and providing a current driver within said device in electrical contact with said voltage multiplier and said applicator electrode for presenting a voltage output sufficient to maintain a defined current at said applicator electrode;

(c) providing said applicator electrode with a prepackaged unit dose of an electrokinetically transportable medicament and a contact surface;

(d) locating the ground electrode on said device for contact by a portion of an individual'"'"'s body whereby the ground electrode serves as a tactile electrode;

(e) placing the contact surface of the applicator electrode into electrical contact with the individual'"'"'s treatment site;

(f) while maintaining the ground electrode in electrical contact with the individual'"'"'s body portion and the contact surface of the applicator electrode in electrical contact with the individual'"'"'s treatment site, causing electrical current to flow through said applicator electrode, the medicament interposed between the applicator electrode and the treatment site, the treatment site, and the tactile electrode by way of the individual'"'"'s treatment site and the individual'"'"'s body portion for electrokinetically motivating said medicament into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source;

(g) incrementally increasing the level of current at the start of the treatment to a predetermined controlled current level;

(h) maintaining electrical current flow at said controlled level until the unit dose of medicament is at least partially depleted and a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site; and

(i) preventing reuse of the applicator electrode after a one-time use thereof.

47. A method according to claim 46 including releasing the prepackaged unit dose of medicament for electrokinetic transport through the contact surface of the applicator electrode into the treatment site.

48. A method of treatment by electrokinetic self-application of a medicament into a treatment site for an individual, comprising the steps of:

(a) providing a portable electrokinetic device having an applicator electrode and a ground electrode in electrical communication with a self-contained electrical power source housed within the device;

(b) providing a voltage multiplier within said device in electrical contact with said power source and said applicator electrode for stepping up the voltage supplied said applicator electrode and providing a current driver within said device in electrical contact with said voltage multiplier and said applicator electrode for presenting a voltage output sufficient to maintain a defined current at said applicator electrode;

(c) providing said applicator electrode with a prepackaged unit dose of an electrokinetically transportable medicament and a contact surface;

(d) locating the ground electrode on said device for contact by a portion of an individual'"'"'s body whereby the ground electrode serves as a tactile electrode;

(e) placing the contact surface of the applicator into electrical contact with the individual'"'"'s treatment site;

(f) while maintaining the ground electrode in electrical contact with the individual'"'"'s body portion and the contact surface of the applicator electrode in electrical contact with the individual'"'"'s treatment site, causing electrical current to flow through said applicator electrode, the medicament interposed between the applicator electrode and the treatment site, the treatment site, and the tactile electrode by way of the individual'"'"'s treatment site and the individual'"'"'s body portion for electrokinetically motivating said medicament into the individual'"'"'s treatment site by the flow of electrical current from said self-contained power source;

(g) incrementally increasing the level of current at the start of the treatment to a predetermined controlled current level;

(h) maintaining electrical current flow at said controlled level until the unit dose of medicament is at least partially depleted and a therapeutically effective dose of said medicament has been transported into the individual'"'"'s treatment site; and

(i) gradually terminating the electrical current to the electrode at the end of the treatment.

49. A method according to claim 48 including preventing reuse of the applicator electrode after a one-time use thereof.

50. A method according to claim 48 including releasing the prepackaged unit dose of medicament for electrokinetic transport through the contact surface of the applicator electrode into the treatment site.

51. A method of treating Herpes Type I and Type II infection in an individual by self-administration of an anti-viral agent, the method comprising the steps of:

(a) providing a portable hand-held electrokinetic device having an applicator electrode in electrical communication with a self-contained electrical power source housed within the device, said applicator electrode including a contact surface and a reservoir containing a unit dose of an electrokinetically transportable anti-viral agent comprising 9-[2-hydroxyethoxy(methyl)]guanine effective for treating Herpes Type I and Type II infection;

(b) releasing the unit dose of the anti-viral agent from the reservoir for electrokinetic transport through the contact surface of the applicator electrode into an individual'"'"'s infection site;

(c) while holding the device, manipulating the device to place the contact surface of the applicator electrode into overlying relation with the individual'"'"'s infection site to enable electrical contact between the applicator electrode and the infection site;

(d) applying from said electrical power source a voltage gradient between the applicator electrode and the infection site to establish electrical contact therebetween by completing an electrical circuit with said power source through the individual'"'"'s hand holding the device, the infection site, the anti-viral agent and the applicator electrode, whereby said anti-viral agent is electrokinetically motivated into the infection site;

(e) incrementally increasing the level of current at the start of the treatment to a predetermined controlled current level;

(f) while holding the device in overlying relation with the infection site, providing the electrical contact between the applicator electrode and the infection site until a therapeutically effective dose of said anti-viral agent has been electrokinetically transported into said infection site; and

(g) preventing reuse of the applicator electrode after a one-time use thereof.