Controlled heat induced rapid delivery of pharmaceuticals from skin depot

• US 6,756,053 B2
• Filed: 06/11/2001
• Issued: 06/29/2004
• Est. Priority Date: 07/28/1995
• Status: Expired due to Fees

• Current Assignee: Nuvo Research AG (Searchlight Pharma, Inc.)
• Original Assignee: Zars, Inc.
• Inventors: Hull, Wade, Zhang, Jie, Rigby, Larry
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Bennett, Rachel M.
• Application Number:
  US09/878,558
• Publication Number:
  US 20020119186A1
• Time in Patent Office: 1,114 Days
• Field of Search: 424/488, 424/499, 424/448, 424/402, 424/443, 424/447, 424/449
• US Class Current: 424/449
• 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: A61F 2013/00187 insulating; warmth or cold applying
• CPC Class Codes: A61F 2013/00204 insulating
• CPC Class Codes: A61F 2013/00906 for transcutaneous or transdermal drugs application
• CPC Class Codes: A61F 2013/0091 with disinfecting or anaesthetics means, e.g. anti-mycrobic
• CPC Class Codes: A61F 7/02 Compresses or poultices for effecting heating or cooling
• CPC Class Codes: A61F 7/032 using oxygen from the air, e.g. pocket-stoves
• CPC Class Codes: A61F 7/034 Flameless
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• 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: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• 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 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• 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: 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: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

The present invention is directed to a method and system for delivering a drug into the systemic circulation. The method comprises establishing a drug depot in a patient'"'"'s skin and/or sub-skin tissues by applying a transdermal drug delivery system on the patients skin, for a predetermined time so that a drug depot is formed in said user'"'"'s skin and/or sub-skin tissues. A heating source is placed proximate to the skin area to rapidly release a bolus of the drug from the depot into the systemic circulation when there is a need to rapidly increase the drug'"'"'s concentrations in the systemic circulation.

Claims

1. A method of delivering a drug into a user'"'"'s systemic circulation, comprising:

establishing a drug depot in tissues under the user'"'"'s skin surface by applying a transdermal drug delivery system on a user'"'"'s skin;

allowing said transdermal drug delivery system to be applied on said skin area without heating for at least a predetermined depot accumulation time so that a drug depot is formed in tissues under the surface of said skin area; and

placing a controlled heating source with a predetermined safe heating duration proximate to said skin area to deliver a predetermined safe dosage of the drug from the depot site into the systemic circulation.

2. The method of claim 1, wherein said drug is capable of providing a clinical benefit to a user if said drug'"'"'s concentrations in said user'"'"'s systemic circulation can be rapidly increased when a clinical need arises.

3. The method of claim 1, wherein said drug is capable of providing certain clinical benefit to a user when said drug'"'"'s concentrations in said user'"'"'s systemic circulation are maintained at pre-determined levels for an extended period of time, and is capable of providing added clinical benefit to said user if its concentrations in said user'"'"'s systemic circulation can be rapidly increased on demand.

4. The method of claim 1, wherein said drug is an analgesic.

5. The method of claim 1, wherein said drug is fentanyl.

6. The method of claim 1, wherein said drug is sufentanil.

7. The method of claim 1, wherein said pe-determined depot accumulation time is about 30 minutes.

8. The method of claim 1, wherein said pre-determined depot accumulation time is at least about one minute.

9. The method of claim 1, wherein said pre-determined depot accumulation time is longer than at least 60 minutes.

10. The method of claim 1, wherein said pre-determined depot accumulation time is about 60 minutes.

11. The method of claim 1, wherein said heating source is capable of heating for a predetermined duration.

12. The method of claim 1, wherein said heating source is capable of heating for a predetermined duration between about 5 seconds and 60 minutes.

13. The method of claim 1, wherein said heating source is capable of heating for a predetermined duration between about 10 seconds to 30 minutes.

14. The method of claim 1, wherein said heating source is capable of heating said skin area to a predetermined temperature range for longer than 60 minutes.

15. The method of claim 1, wherein said heating source is capable of heating said skin area to a predetermined temperature range for a predetermined duration of between about 5 seconds to 60 minutes.

16. The method of claim 15, wherein said predetermined temperature range is between about 39-43 C.

17. The method of claim 15, wherein said predetermined temperature range is between about 39-43 C.

18. A method to provide baseline concentrations of an analgesic in a human being'"'"'s systemic circulation and to rapidly deliver a bolus dose of said analgesic into said systemic circulation when said human being is suffering from an increased level of pain, comprising:

applying a transdermal analgesic delivery system onto a skin area of a human being to establish baseline concentrations of said analgesic in said human being'"'"'s blood;

allowing said transdermal analgesic delivery system to be applied without heating for a time sufficient to allow the formation of an analgesic depot in tissues under the surface of said skin area of said human being; and

placing a heating source proximate to said skin area when said human being suffers from increased level of pain.

19. A method of delivering a drug into the systemic circulation of a human being, comprising:

establishing a drug depot in tissues under the surface of a skin area by applying a transdermal drug delivery system on the skin area of a human being and heating said skin area to a first temperature range for a predetermined depot accumulation time;

allowing said transdermal drug delivery system to be applied while heating said skin area to said first temperature range for a predetermined depot accumulation time; and

heating said skin area to a second temperature range, which is higher than said first temperature range, for a second pre-determined period of time.

20. A method to provide baseline concentrations of fentanyl in a human being'"'"'s systemic circulation and to rapidly deliver a bolus dose of fentanyl into said systemic circulation when said human being is suffering from an increased level of pain, comprising:

applying a transdermal fentanyl delivery system onto a skin area of a human being to establish baseline concentrations of fentanyl in said human being'"'"'s blood;

allowing said transdermal fentanyl delivery system to be applied without heating for a time sufficient to allow the formation of a fentanyl depot in tissues under the surface of said skin area of the said human being; and

placing a heating source proximate to said skin area when said human being suffers from increased level of pain.

21. A method to provide baseline concentrations of sufentanil in a human being'"'"'s systemic circulation and to rapidly deliver a bolus dose of sufentanil into said systemic circulation when said human being is suffering from an increased level of pain, comprising:

applying a transdermal sufentanil delivery system onto a skin area of a human being to establish baseline concentrations of sufentanil in said human being'"'"'s blood allowing said transdermal sufentanil delivery system to be applied without heating for a time sufficient to allow the formation of a sufentanil depot in tissues under the surface of said skin area of the said human being; and

placing a heating source proximate to said skin area when said human being suffers from increased level of pain.