Method and apparatus for delivery of therapeutic agents

• US 20070021712A1
• Filed: 03/14/2006
• Published: 01/25/2007
• Est. Priority Date: 04/05/2002
• Status: Active Grant

• Current Assignee: Ichor Medical Systems, Inc.
• Original Assignee: Ichor Medical Systems, Inc.
• Inventors: Bernard, Robert, Bernard, Brady, Hannaman, Andrew
• Granted Patent: US 8,187,249 B2
• Time in Patent Office: Days
• US Class Current: 604/21
• CPC Class Codes: A61M 2005/206 With automatic needle insertion
• CPC Class Codes: A61M 5/20 Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically A61M5/142 , A61M5/46 take precedence; hypodermic projectiles F42B12/54
• CPC Class Codes: A61M 5/2033 Spring-loaded one-shot injectors with or without automatic needle insertion multishot dosing syringes A61M5/31525, needle insertion only A61M5/3287
• CPC Class Codes: A61M 5/2053 Media being expelled from injector by pressurised fluid or vacuum for infusion A61M5/145, A61M5/155
• CPC Class Codes: A61M 5/30 Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
• CPC Class Codes: A61M 5/326 Fully automatic sleeve extension, i.e. in which triggering of the sleeve does not require a deliberate action by the user
• CPC Class Codes: A61M 5/46 having means for controlling depth of insertion
• 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 1/306 Arrangements where at least part of the apparatus is introduced into the body

Abstract

Methods and apparatus for the reproducible, consistent and efficacious delivery of a therapeutic agent to a patient. The invention comprises means for the controlled administration of the therapeutic agent through an orifice to the patient, a plurality of penetrating electrodes arranged with a predetermined spatial relationship relative to the orifice, and means for generating an electrical signal operatively connected to the electrodes.

Claims

1-17. -17. (canceled)

18. A method for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising the steps of:

inserting a plurality of penetrating electrodes in the tissue of a patient to substantially encompass a predetermined tissue site;

contacting said patient with an injection orifice according to a pre-determined spatial relationship with said electrodes, wherein said injection orifice is located within the tissue region bounded by said electrodes;

administering a therapeutic agent to said patient through said orifice such that the agent is distributed within said predetermined tissue site encompassed by said electrodes;

applying an electrical signal to at least two of said electrodes such that the resulting electric field propagation in said predetermined tissue site is of sufficient magnitude and duration to increase the intracellular uptake of said therapeutic agent.

19. The method of claim 18 wherein a template is used to control the spatial relationship between said injection orifice and said electrodes in the tissue of said patient

20. The method of claim 18 wherein said therapeutic agent is a nucleic acid.

21. The method of claim 20 wherein the nucleic acid is DNA.

22. The method of claim 18 wherein said predetermined tissue site is located in a skeletal muscle of said patient.

23. The method of claim 22 wherein said electrical signal comprises at least one monopolar direct current pulse.

24. The method of claim 23 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

25. The method of claim 23 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said electrodes.

26. A method for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising the steps of:

inserting a plurality of penetrating electrodes in the tissue of a patient to substantially encompass a predetermined tissue site;

contacting said patient with an injection orifice;

administering a therapeutic agent through said orifice to said predetermined tissue site encompassed by said electrodes, wherein the rate of agent administration is controlled by an inanimate source of energy;

applying an electrical signal to at least two of said electrodes such that the resulting electric field propagation in said predetermined tissue site is of sufficient magnitude and duration to increase the intracellular uptake of said therapeutic agent.

27. The method of claim 26 wherein a template is used to control the spatial relationship between said injection orifice and said electrodes in the tissue of said patient.

28. The method of claim 26 wherein said inanimate source of energy is a spring.

29. The method of claim 26 wherein said inanimate source of energy is a compressed gas.

32. The method of claim 26 wherein said predetermined tissue site is located in a skeletal muscle of said patient.

33. The method of claim 26 wherein said electrical signal comprises at least one monopolar direct current pulse.

34. The method of claim 33 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

35. The method of claim 33 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said electrodes.

36. A method for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising the steps of:

contacting a patient with an injection orifice;

administering a therapeutic agent to said patient through said orifice such that the agent is distributed within a predetermined tissue site;

contacting said patient with a device that houses a plurality of electrodes in a retracted state such that the electrodes are not visible to the patient;

deploying said plurality of electrodes from their retracted state into the tissue of said patient so as to substantially encompass said predetermined tissue site;

applying an electrical signal to at least two of said electrodes such that the resulting electric field propagation in said predetermined tissue site is of sufficient magnitude and duration to increase the intracellular uptake of said therapeutic agent.

37. The method of claim 36 wherein deployment of said electrodes is mediated by an inanimate source of energy.

38. The method of claim 37 wherein said inanimate source of energy is a spring.

39. The method of claim 37 wherein said inanimate source of energy is a compressed gas.

40. The method of claim 36 wherein said therapeutic agent is a nucleic acid.

41. The method of claim 40 wherein the nucleic acid is DNA.

42. The method of claim 36 wherein said predetermined tissue site is located in a skeletal muscle of said patient.

43. The method of claim 36 wherein said electrical signal comprises at least one monopolar direct current pulse.

44. The method of claim 43 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

45. The method of claim 43 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said electrodes.

46. A method for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising the steps of:

contacting a patient with a device that houses an injection orifice and a plurality of electrodes in a retracted state such that the electrodes are not visible to the patient;

deploying said plurality of electrodes from their retracted state into the tissue of said patient to substantially encompass a predetermined tissue site;

administering a therapeutic agent to said patient through said orifice such that the agent is distributed within said predetermined tissue site;

applying an electrical signal to at least two of said electrodes such that the resulting electric field propagation in said predetermined tissue site is of sufficient magnitude and duration to increase the intracellular uptake of said therapeutic agent.

47. The method of claim 46 wherein deployment of said electrodes is mediated by an inanimate source of energy.

48. The method of claim 47 wherein said inanimate source of energy is a spring.

49. The method of claim 47 wherein said inanimate source of energy is a compressed gas.

50. The method of claim 46 wherein said therapeutic agent is a nucleic acid.

51. The method of claim 50 wherein the nucleic acid is DNA.

52. The method of claim 46 wherein said predetermined tissue site is located in a skeletal muscle of said patient.

53. The method of claim 46 wherein said electrical signal comprises at least one monopolar direct current pulse.

54. The method of claim 53 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

55. The method of claim 53 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said electrodes.