Transdermal protein delivery using low-frequency sonophoresis

• US 6,002,961 A
• Filed: 07/25/1995
• Issued: 12/14/1999
• Est. Priority Date: 07/25/1995
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Mitragotri, Samir S., Blankschtein, Daniel
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US08/507,060
• Time in Patent Office: 1,603 Days
• Field of Search: 604/20, 601/2, 424/448, 424/449
• 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 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428

Abstract

Applications of low-frequency (20 KHz) ultrasound enhances transdermal transport of high-molecular weight proteins. This method includes a simultaneous application of ultrasound and protein on the skin surface in order to deliver therapeutic doses of proteins across the skin. Examples demonstrate in vitro and in vivo administration of insulin (molecular weight 6,000 D), and in vitro administration of gamma interferon (molecular weight 17,000 D), and erythropoeitin (molecular weight 48,000 D).

Claims

1. A method for enhancing delivery of a drug in a single step across the skin into the blood using ultrasound wherein the ultrasound is applied by pulsing at a frequency of between 20 kHz and less than 1 MHz at an intensity not causing any irreversible skin damage for a period of time effective to deliver to the patient a therapeutic drug dosage into the blood.

2. The method of claim 1 wherein the drug is a peptide or protein.

3. The method of claim 1 wherein an effective amount of drug is administered in less than one hour.

4. The method of claim 1 wherein the frequency is between 20 and 45 kHz.

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

6. The method of claim 5 wherein the intensity is between 12.5 mW/cm² and 225 mW/cm².