Ultrasound-enhanced delivery of materials into and through the skin

• US 5,323,769 A
• Filed: 08/02/1993
• Issued: 06/28/1994
• Est. Priority Date: 02/23/1990
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Cygnus Therapeutic Systems, Regents of the University of California (University of California)
• Inventors: Okuyama, Hirohisa, Flynn, Gordon L., Guy, Richard H., Stauffer, Paul, Bommannan, Durairaj
• Primary Examiner(s): Cohan, Lee S.
• Assistant Examiner(s): ZELE, KRISTA MICHELLE
• Application Number:
  US08/101,491
• Time in Patent Office: 330 Days
• Field of Search: 128/24 AA, 128/660.03, 604/20, 604/22
• US Class Current: 601/2
• CPC Class Codes: A61B 10/00 Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis vaccination prophylaxis, vaccination therapy A61B17/20; Sex determination; Ovulation-period determination menstruation tables G06C3/00; Throat striking implements
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 10/02 Instruments for taking cell samples or for biopsy A61B10/0038 and A61B10/0045 take precedence; needle locating or guiding means A61B17/3403; samplers for enzymology or microbiology C12M1/26; sampling or preparing biological specimens G01N33/48
• CPC Class Codes: A61B 2017/00765 Decreasing the barrier function of skin tissue by radiated energy, e.g. using ultrasound, using laser for skin perforation
• 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 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092
• CPC Class Codes: A61N 7/02 Localised ultrasound hyperthermia hyperthermia in general A61F7/00

Abstract

A method for enhancing the permeability of the skin or other biological membrane to a material such as a drug is disclosed. In the method, the drug is delivered in conjunction with ultrasound having a frequency of above about 10 MHz. The method may also be used in conjunction with chemical permeation enhancers and/or with iontophoresis.

Claims

1. A method for enhancing the rate of permeation of a drug medium into a selected intact area of an individual'"'"'s body surface, which method comprises:

(a) applying ultrasound having a frequency of above 10 MHz to said selected area, at an intensity and for a period of time effective to enhance the permeability of said selected area;

(b) contacting the selected area with the drug medium; and

(c) effecting passage of said drug medium into and through said selected area by means of iontophoresis.

2. The method of claim 1, wherein said ultrasound frequency is in the range of about 15 MHz to 50 MHz.

3. The method of claim 2, wherein said ultrasound frequency is in the range of about 15 to 25 MHz.

4. The method of claim 1, wherein said period of time is in the range of about 5 to 45 minutes.

5. The method of claim 4, wherein said period of time is in the range of about 5 to 30 minutes.

6. The method of claim 1, wherein said period of time is less than about 10 minutes.

7. The method of claim 1, wherein said intensity of said ultrasound is less than about 5.0 W/cm².

8. The method of claim 7, wherein said intensity of said ultrasound is in the range of about 0.01 to 5.0 W/cm².

9. The method of claim 8, wherein said intensity of said ultrasound is in the range of about 0.05 to 3.0 W/cm².

10. The method of claim 1, wherein said area of the stratum corneum is in the range of about 1 to 100 cm².

11. The method of claim 10, wherein said area of the stratum corneum is in the range of about 5 to 100 cm².

12. The method of claim 11, wherein said area of the stratum corneum is in the range of about 10 to 50 cm².

13. The method of claim 1 wherein said drug medium comprises a drug and a coupling agent effective to transfer said ultrasound to the body from an ultrasound source.

14. The method of claim 13 wherein said coupling agent is a polymer or a gel.

15. The method of claim 13 wherein said coupling agent is selected from the group consisting of glycerin, water, and propylene glycol.

16. The method of claim 1 wherein said drug medium further comprises a chemical permeation enhancer.

17. The method of claim 1, wherein steps (a) and (b) are carried out approximately simultaneously.

18. The method of claim 1, wherein step (b) is carried out before step (a).

19. The method of claim 1, wherein step (a) is carried out before step (b).

20. The method of claim 1, wherein the ultrasound is applied continuously.

21. The method of claim 1, wherein the ultrasound is pulsed.