Ultrasound-enhanced delivery of materials into and through the skin

• US 5,115,805 A
• Filed: 02/23/1990
• Issued: 05/26/1992
• Est. Priority Date: 02/23/1990
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson), Regents of the University of California (University of California)
• 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): Cohen, Lee S.
• Assistant Examiner(s): Pfaffle, Krista M.
• Application Number:
  US07/484,560
• Time in Patent Office: 823 Days
• Field of Search: 128/24 AA, 128/660.03, 604/20
• 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) contacting the selected intact area with the drug medium; and

(b) applying ultrasound having a frequency of above 10 MHz to said selected area for a treatment time in the range of about 30 seconds to 60 minutes at an intensity effective to enhance the rate of permeation.

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

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

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

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

6. The method of claim 5, wherein said treatment time is less than about 10 minutes.

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

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

9. The method of claim 8, wherein the 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 selected intact area of skin is in the range of about 1 to 100 cm².

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

12. The method of claim 11, wherein said selected intact area of skin 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 said body surface 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 13, wherein said drug is a proteinaceous drug.

17. The method of claim 13, wherein the drug medium further comprises a chemical permeation enhancer.

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

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

20. The method of claim 1, wherein step (a) is carried out prior to step (b).

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

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

23. A method for enhancing the rate of permeation of a drug medium through a biological membrane, comprising the steps of:

(a) contacting the biological membrane with the drug medium; and

(b) applying ultrasound to the drug medium and membrane, the ultrasound having a frequency of above 10 MHz and being applied for a treatment time in the range of about 30 seconds to 60 minutes at an intensity sufficient to enhance the rate of permeation of the drug medium through the membrane.

24. The method as claimed in claim 23, wherein the frequency is of at least 15 MHz.

25. The method of claim 23, wherein said ultrasound has a frequency in the range of about 15 MHz to 50 MHz.

26. The method of claim 25, wherein said ultrasound has a frequency in the range of about 15 to 25 MHz.