Apparatus for heating to a desired temperature for improved administration of pharmaceutically active compounds

• US 6,306,431 B1
• Filed: 04/07/2000
• Issued: 10/23/2001
• Est. Priority Date: 07/28/1995
• Status: Expired due to Term

• Current Assignee: Nuvo Research AG (Searchlight Pharma, Inc.)
• Original Assignee: Zars, Inc.
• Inventors: Zhang, Hao, Zhang, Jie
• Primary Examiner(s): Dees, Jose′ G.
• Assistant Examiner(s): Williamson, Michael A.
• Application Number:
  US09/545,497
• Time in Patent Office: 564 Days
• Field of Search: 424/402, 424/443, 424/447, 424/448, 424/449, 514/817, 514/937, 514/944, 602/41, 602/46
• US Class Current: 424/449
• 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 7/032 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

Abstract

Methods and apparatus for improving administration of drugs through the use of heat and other physical means. The present invention relates to the use of heat and other physical means in conjunction with specially designed dermal drug delivery systems, conventional commercial dermal drug delivery systems, or drugs delivered into a sub-skin depot site via injection and other methods to alter, mainly increase, the drug release rate from the dermal drug delivery systems or the depot sites to accommodate certain clinical needs.

Claims

1. An apparatus capable of heating to a desired narrow temperature range for a desired length of time comprising:

a shallow chamber defined by an air impermeable wall having an opening and a cover capable of covering said opening, said covering having a desired air permeability, and

a heat generating medium disposed within said shallow chamber of said apparatus, said apparatus capable of generating controlled heat by exposing an oxygen activated exothermic medium within the apparatus to oxygen and varying the amount of oxygen to which the exothermic medium is exposed to vary a rate of reaction of the exothermic medium.

2. The apparatus of claim 1, wherein said heat generating medium comprises activated carbon, iron powder and water.

3. The apparatus of claim 1, wherein said apparatus facilitates transdermal absorption of a pharmaceutical.

4. The apparatus of claim 1, wherein said heating facilitates absorption of an active ingredient in a dermal drug delivery system.

5. The apparatus of claim 1, wherein said heating increases the speed of drug transport to a patient'"'"'s systemic circulation from at least one storage site under the patient'"'"'s skin.

6. The apparatus of claim 1, wherein said heating increases the speed of drug transport to a patient'"'"'s systemic circulation from a dermal drug delivery system.

7. The apparatus of claim 1, wherein said heating increases the solubility of an active ingredient in a formulation of a dermal drug delivery system to increase transdermal absorption of said active ingredient.

8. The apparatus of claim 1, wherein said heating controls the speed of transport of a pharmaceutically active ingredient from a storage site in the human body.

9. The method of claim 1, wherein said storage site is within about 5 centimeters from a patient'"'"'s skin surface.

10. The apparatus of claim 1, wherein said heating shortens the onset time of pharmaceutical delivered by a dermal drug delivery system.

11. The apparatus of claim 1, wherein said desired length of time is long enough to cause at least about a 20% increase in the quantity of an active ingredient transported from a dermal drug delivery system into a patient'"'"'s body when compared with transport of said active ingredient without heating.

12. The apparatus of claim 11, wherein said about 20% increase occurs within about the first 10 hours of heating.

13. The apparatus of claim 11, wherein said 20% increase occurs within about the first 7 hours of heating.

14. The apparatus of claim 11, wherein said about 20% increase occurs within about the first 4 hours of heating.

15. The apparatus of claim 1, wherein said desired length of time is based on the effect of a delivered pharmaceutical.

16. The apparatus of claim 1, wherein said apparatus is for heating human skin.

17. The apparatus of claim 1, wherein said apparatus heats a rate limiting membrane and a pharmaceutical formulation disposed within a dermal drug delivery system.

18. The apparatus of claim 1, wherein said apparatus heats at least one storage site beneath a patient'"'"'s skin.

19. The apparatus of claim 1, wherein said apparatus is for heating a pharmaceutical formulation.

20. The apparatus of claim 1, wherein said narrow temperature range is below a temperature of about 60°

centigrade.

21. The apparatus of claim 1, wherein said narrow temperature range is between about 38°

and about 45°

centigrade.

22. The apparatus of claim 1, wherein said temperature range is between about 39°

centigrade to about 43°

centigrade.

23. The apparatus of claim 1, wherein said desired length of time is between about 3 minutes to about 7 days.

24. The apparatus of claim 1, wherein said desired length of time is about 10 minutes to about 72 hours.

25. The apparatus of claim 1, wherein said desired length of time is about 20 minutes to about 24 hours.

26. The apparatus of claim 1, wherein said length of time is based upon the effect of a pharmaceutical agent.

27. The apparatus of claim 1, wherein said apparatus further comprises means for affixing said shallow chamber.

28. The apparatus of claim 27, wherein said means for affixing comprises an adhesive area on a portion of a surface of said shallow chamber.

29. The apparatus of claim 27, wherein said apparatus further comprises means to facilitate removal of said shallow chamber from a DDS on human skin without removing said DDS from said healing skin.

30. The apparatus of claim 29, wherein said means to facilitate removal comprises an adhesive area of a portion of the surface of said shallow chamber and a less adhesive area on a portion of a surface of said shallow chamber.