Effect of electric field and ultrasound for transdermal drug delivery

• US 6,041,253 A
• Filed: 04/01/1996
• Issued: 03/21/2000
• Est. Priority Date: 12/18/1995
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Mitragotri, Samir S., Langer, Robert S., Kost, Joseph, Weaver, James C., Pliquett, Uwe
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US08/626,021
• Time in Patent Office: 1,450 Days
• Field of Search: 604/20, 604/22, 604/49, 601/2, 128/760, 128/637, 600/573, 600/578
• US Class Current: 604/20
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• 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: 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 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 1/042 Material of the electrode
• CPC Class Codes: A61N 1/0428 Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.

Claims

1. A method for enhancing transdermal transport of compounds comprising administering to the skin an effective amount of ultrasound at a frequency of less than 2.5 MHz to permeabilize the skin followed by an enhancer selected from the group consisting of electroporation, vacuum or mechanical pressure.

2. The method of claim 1 comprising administering to the skin an effective amount of ultrasound at a frequency of less than 2.5 MHz in combination with electroporation at a voltage of between about 20 V and about 150 V followed by the application of a vacuum or mechanical pressure.

3. The method of claim 1 wherein the ultrasound is administered at a frequency of 1 MHz or less.

4. The method of claim 1 wherein the intensity of the ultrasound is less than the maximum intensity that will not cause permanent skin damage.

5. The method of claim 1 wherein the intensity of the ultrasound is less than 2.5 W/cm².

6. The method of claim 1 comprising administering to the skin an effective amount of ultrasound at a frequency of less than 2.5 MHz followed by electroporation to effect transdermal transport.

7. The method of claim 1 wherein the ultrasound is followed by administration of vacuumn or mechanical pressure.

8. The method of claim 1 wherein the compound to be transported is a drug the patient is in need of.

9. The method of claim 1 wherein the compound to be transported is an analyte to be measured.

10. The method of claim 1 wherein the ultrasound is pulsed.