Method for transdermal delivery of permeant substances

• US 8,016,811 B2
• Filed: 10/24/2003
• Issued: 09/13/2011
• Est. Priority Date: 10/24/2003
• Status: Active Grant

• Current Assignee: ​Passport Technologies, Inc.
• Original Assignee: Altea Therapeutics Corporation (Nitto Denko Corporation)
• Inventors: Smith, Alan, Novakovic, Zoran, Messier, Bernadette, McRae, Stuart, Eppstein, Jonathan A.
• Primary Examiner(s): STIGELL, THEODORE J
• Application Number:
  US10/691,968
• Publication Number:
  US 20050090800A1
• Time in Patent Office: 2,881 Days
• Field of Search: 604/20, 604/500, 604/501, 606/27
• US Class Current: 604/501
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0046 Ear
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• 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 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

A method for delivering permeant substances transdermally into a membrane of an animal includes forming at least one delivery opening in the skin tissue, with the at least one delivery opening having a mean opening depth of between about 40 and about 90 microns.

Claims

1. A method for delivering permeant substances through a biological membrane of an animal comprising applying at least one heated probe element capable of conductively delivering thermal energy via direct contact to the biological membrane to cause the ablation of some portion of the membrane to form a plurality of delivery openings in the membrane, wherein an opening depth of the majority of said delivery openings falls within the range between about 40 and about 90 microns, delivering a permeant by placing a patch comprising a permeant over the plurality of delivery openings, and characterizing the depth by a means selected from the group consisting of, a microscope and digital depth indicator, infusion of a tracer compound, and trans-epidermal water loss measurement (TEWL).

2. The method of claim 1 wherein the opening depth of a majority of said delivery openings falls within the range of about 50 to about 70 microns.

3. The method of claim 2 wherein 75% of said delivery openings have an opening depth falling within the range of about 50 to about 70 microns.

4. The method of claim 3 wherein 75% of said delivery openings have an opening depth falling within the range of about 55 microns to about 65 microns.

5. The method of claim 1 wherein said delivery openings have a range of opening depths falling within one standard deviation of about 50 microns to about 70 microns.

6. The method of claim 5 wherein said delivery openings have a range of opening depths falling within one standard deviation of about 60 microns.

7. The method of claim 1 wherein said delivery openings have a range of opening depths falling within one standard deviation of about 90 microns.

8. The method of claim 1 wherein the plurality of delivery openings are formed by a planar array microporation device.

9. The method of claim 1 wherein the heated probe comprises an electrically heated resistive element capable of ablating the biological membrane.

10. The method of claim 1 wherein the plurality of delivery openings are formed by microporation conducted with positive pressure being present between a microporator and said membrane.

11. The method of claim 10 wherein said positive pressure is applied manually by pressing down on said microporator when being activated.

12. The method of claim 10 wherein said positive pressure results from a vacuum of about 0.25 to about 0.80 bar being applied between said microporator and said membrane.

13. The method of claim 12 wherein said vacuum is about 0.50 bar.

14. The method of claim 1 wherein said delivery of said permeant substance results in a blood serum profile for said permeant substance that mimics a blood serum profile as if the permeant substance had been delivered subcutaneously.

15. The method of claim 1 wherein said biological membrane is skin.

16. The method of claim 1 wherein said permeant is insulin.

17. The method of claim 1 wherein said permeant is hydromorphone.

18. A method for delivering drugs transdermally into a biological membrane of an animal comprising ablating a plurality of delivery openings through a membrane, wherein said delivery openings have a distribution resulting in a bell-shaped curve with said delivery openings having a mean opening depth of between about 40 and about 90 microns, delivering a drug by placing a patch comprising a drug over the plurality of delivery openings, and characterizing the depth by a means selected from the group consisting of, a microscope and digital depth indicator, infusion of a tracer compound, and trans-epidermal water loss measurement (TEWL).

19. The method of claim 18 wherein said delivery openings have a mean opening depth of about 50 and about 70 microns.

20. The method of claim 19 wherein said delivery openings have a mean opening depth of about 55 to about 65 microns.

21. The method of claim 20 wherein said delivery openings have a mean opening depth of about 60 microns.

22. The method of claim 18 wherein said delivery openings have a mean opening depth of about 90 microns.

23. The method of claim 18 wherein a majority of said delivery openings have a mean opening depth falling within the range of about 40 and about 90 microns.

24. The method of claim 23 wherein the opening depth of a majority of said delivery openings falls within the range of about 50 to about 70 microns.

25. The method of claim 24 wherein 75% of said delivery openings have an opening depth falling within the range of about 50 to about 70 microns.

26. The method of claim 25 wherein 75% of said delivery openings have an opening depth falling within the range of about 55 microns to about 65 microns.

27. The method of claim 23 wherein said delivery openings have a range of opening depths falling within one standard deviation of about 50 microns to about 70 microns.

28. The method of claim 27 wherein said delivery openings have a range of opening depths falling within one standard deviation of about 60 microns.

29. The method of claim 18 wherein said delivery openings have a range of opening depths falling within one standard deviation of about 90 microns.

30. The method of claim 18 wherein said delivery openings is formed by a planar array microporation device.

31. The method of claim 18 wherein said delivery openings are formed by a microporator comprising a heated probe element capable of conductively delivering thermal energy via direct contact to a biological membrane to cause the ablation of some portion of the membrane deep enough to form a micropore.

32. The method of claim 31, wherein the heated probe comprises an electrically heated resistive element capable of ablating the biological membrane.

33. The method of claim 18 wherein said delivery openings are formed by microporation conducted with positive pressure being present between a microporator and said membrane.

34. The method of claim 33 wherein said positive pressure is applied manually by pressing down on said microporator when being activated.

35. The method of claim 33 wherein said positive pressure results from a vacuum of about 0.25 to about 0.80 bar being applied between said microporator and said membrane.

36. The method of claim 35 wherein said vacuum is about 0.50 bar.

37. The method of claim 18 wherein said delivery of said permeant substance results in a blood serum profile for said permeant substance that mimics a blood serum profile as if the permeant substance had been delivered subcutaneously.

38. The method of claim 18 wherein said biological membrane is skin.

39. The method of claim 18 wherein said permeant is insulin.

40. The method of claim 18 wherein said permeant is hydromorphone.