Irradiation enhanced permeation and delivery

• US 6,419,642 B1
• Filed: 06/08/2000
• Issued: 07/16/2002
• Est. Priority Date: 09/24/1993
• Status: Expired due to Fees

• Current Assignee: Transmedica International Incorporated
• Original Assignee: Transmedica International Incorporated
• Inventors: Marchitto, Kevin S., Flock, Stephen T.
• Primary Examiner(s): Shaver, Kevin
• Assistant Examiner(s): ASTORINO, MICHAEL C
• Application Number:
  US09/589,865
• Time in Patent Office: 768 Days
• Field of Search: 606/9-17, 606/2-3, 600/573, 128/897-898, 604/20, 607/89, 607/88
• US Class Current: 600/573
• CPC Class Codes: A61B 17/3476 Powered trocars, e.g. electrosurgical cutting, lasers, powered knives
• CPC Class Codes: A61B 18/20 using laser
• CPC Class Codes: A61B 18/203 applying laser energy to the outside of the body
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 2017/00057 Light
• 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: A61B 2018/00452 Skin
• CPC Class Codes: A61B 2090/395 with marking agent for marking skin or other tissue
• CPC Class Codes: A61B 2218/008 for smoke evacuation
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150076 by heating
• CPC Class Codes: A61B 5/150099 by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
• CPC Class Codes: A61B 5/15138 provided with means to ensure the protection of the user, e.g. to avoid laser light entering the eyes of a user
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• 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 37/00 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: H04R 25/75 Electric tinnitus maskers providing an auditory perception

Abstract

The present invention provides a method of delivering substances for permeation through the skin of a subject, by energizing the stratum corneum in conjunction with various delivery means including gels and patches. Permeability enhancement or reduced electrical impedance of the skin, increases the variety of substances capable of permeation, and increases the permeation rate and the effectiveness of the permeation, including permeation enhanced by iontophoresis. The method allows for the use of improved delivery means that were previously unavailable.

Claims

1. A method of introducing a substance into a living body, comprising:

forming an area on the stratum corneum of the skin of a living body having enhanced permeability through to the capillary layer by irradiating the skin with subablative laser energy without substantially ablating the skin; and

introducing the substance into the body by bringing the substance in contact with the area of enhanced permeability.

2. The method of claim 1, wherein forming the area comprises:

irradiating the skin with laser energy selected from the group consisting of Er;

YAG, pulsed CO₂, Ho;

YAG, Er;

YAP, Er/Cr;

YSGG, Ho;

YSGG, Er;

GGSG, Er;

YLF, Tm;

YAG, Ho/Nd;

YA 10₃, cobalt;

MgF₂, HF chemical, DF chemical, carbon monoxide, deep LJV laser, diode laser, frequency tripled Nd;

YAG, and combinations thereof.

3. The method of claim 2, wherein irradiating the skin comprises:

irradiating the skin with subablative laser energy having a wavelength of about 1.5 to about 10 microns, an energy fluence of about 0.1 to about 100,000 J/cm², and a target area on the skin of about 0.001 to about 10 mm in diameter.

4. The method of claim 3, wherein irradiating the skin comprises;

irradiating the skin with subablative laser energy having a wavelength of approximately 2.94 microns.

5. The method of claim 1, wherein forming the area comprises:

irradiating the skin with laser energy selected from the group consisting of gated, continuous wave, modulated diode, or pulsed laser radiant energy.

6. The method of claim 5, wherein irradiating the skin comprises:

irradiating the skin with subablative laser energy having a wavelength of about 1.5 to about 10 microns, an energy fluence of about 0.1 to about 100,000 J/cm², and a target area on the skin of about 0.001 to about 10 mm in diameter.

7. The method of claim 6, wherein irradiating the skin comprises;

irradiating the skin with subablative laser energy having a wavelength of approximately 2.94 microns.

8. The method of claim 1, wherein the substance is selected from the group of in vivo diagnostic substances consisting of contrasting imaging agents, radionuclide based agents, and combinations thereof.

9. The method of claim 1, wherein the substance is selected from the group of systemically active substances consisting of neuroactive agents, auto acids, anti-hypertensives, anti-arrhythmics, hormones, chemotherapy antiparasitic agents, chemotherapy anti-microbial agents, and combinations thereof.

10. The method of claim 1, wherein the substance is selected from the group of locally active substances consisting of lidocaine, anesthetic agents, erectile dysfunction agents, metabolic inhibitors, steroidal or nonsteroidal anti-inflammatory agents, vitamins, retinoids, anticancer agents, antibodies, antibody conjugates, and combinations thereof.

11. The method of claim 1, wherein the substance is selected from the group consisting of protein based pharmaceutical substances, DNA based pharmaceutical substances, RNA based pharmaceutical substances, and combinations thereof.

12. The method of claim 11, wherein the protein based substance is selected from the group consisting of cytokines, hormones, cell activation factors, cellular inhibitors, proteases, protease inhibitors, clotting factors, and combinations thereof.

13. The method of claim 11, wherein the DNA or RNA based substance is selected from the group consisting of oligonucleotides, gene therapy agents, ribozymes, and combinations thereof.

14. The method of claim 1, wherein the substance is selected from the group of antimicrobial chemotherapy agents consisting of anti-infectives, antifungals, antivirals, and combinations thereof.

15. The method of claim 1, wherein the substance is selected from the group of immunity generating substances consisting of vaccines, antigens, immunogen preparations, and combinations thereof.

16. The method of claim 1, wherein the substance is selected from the group of permeation enhancing substances consisting of dimethyl-sulfoxide, alcohol, Azone, pentaerythritrol dioleat, lauramide DEA, polyethyleneglycol-10 laurate, nonoxynol-10, propylene glycol, urea, water, n-propanol, amines, amides, pyrrolidones, surfactants, fatty acids, liposomes, and combinations thereof.

17. The method of claim 1, wherein bringing the substance in contact with the area of enhanced permeability comprises:

bringing the substance in direct contact with interstitial fluid from within the body.