Method for reducing onset time of pharmaceutically active compounds

• US 6,340,472 B1
• Filed: 04/07/2000
• Issued: 01/22/2002
• 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): Qazi, Sabiha
• Assistant Examiner(s): Williamson, Michael A.
• Application Number:
  US09/545,495
• Time in Patent Office: 655 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: 424/448
• 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. A method of reducing an onset time of the effect of a drug in a target area of a human body comprising:

administering a drug to a portion if said human body;

applying a temperature of modification apparatus proximate said drug being administered, said temperature modification 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; and

adjusting the temperature of skin proximate said portion of said human body with said temperature modification apparatus to achieve said reduces onset time of said drug in said targeted area.

2. The method of claim 1, wherein said targeted area of said human body comprises a systemic bloodstream.

3. The method of claim 1, wherein said targeted area of said human body comprises a body tissue region proximate a location of said administering of said drug.

4. The method of claim 1, wherein said administering said drug to said portion of said human body includes applying said drug transdermally.

5. The method of claim 4, wherein said applying said drug transdermally is effectuated by applying a dermal drug delivery system to the skin of said portion of said human body.

6. The method of claim 1, wherein said applying said temperature modification apparatus proximate said administered drug comprises applying said temperature modification apparatus to said dermal drug delivery system.

7. The method of claim 1, wherein said administering said drug to said portion of said human body includes depositing said drug into the skin of said human body.

8. The method of claim 7, wherein said depositing said drug subcutaneously comprises a delivery method selected from the group consisting of:

injection, implantation, iontophoresis, electroportion, hitting said drug into portion of said patient'"'"'s body with supersonic speed, ultrasound assist transdermal permeation, and embedding said drug.

9. The method of claim 7, wherein said depositing said drug into the skin of said human body comprises depositing a sustained release drug into the skin of said human body.

10. The method of claim 9, wherein said depositing said sustained release drug subcutaneously comprises depositing said drug incorporated in a biodegradable, biocompatible polymer.

11. The method of claim 10, wherein said biodegradable, biocompatible polymer is a polymer of lactic and glycolic acid.

12. The method of claim 10, wherein said biodegradable, biocompatible polymer is a copolymer of lactic and glycolic acid.

13. The method of claim 10, wherein said biodegradable, biocompatible polymer is selected from the group consisting of poly(DL-lactide), poly(DL-lactide-co-glycolide), poly(DL-lactide-co-ε

-caprolactone), polycaprolactone, and combinations thereof.

14. The method of claim 1, wherein said administering said drug to said portion of said human body includes depositing said drug into tissues under the skin of said human body.

15. The method of claim 14, wherein said depositing said drug into tissues under the skin of said human body comprises a delivery method selected from the group consisting of:

injection, implantation, iontophoresis, electroportion, hitting said drug into portion of said patient'"'"'s body with supersonic speed, ultrasound assist transdermal permeation, and embedding said drug.

16. The method of claim 14, wherein said depositing said drug into tissues under the skin of said human body comprises depositing a sustained release drug into tissues under the skin of said human body.

17. The method of claim 16, wherein said depositing said sustained release drug under the skin of said human body comprises depositing said drug incorporated in a biodegradable, biocompatible polymer.

18. The method of claim 17, wherein said biodegradable, biocompatible polymer is a polymer of lactic and glycolic acid.

19. The method of claim 17, wherein said biodegradable, biocompatible polymer is a copolymer of lactic and glycolic acid.

20. The method of claim 17, wherein said biodegradable, biocompatible polymer is selected from the group consisting of poly(DL-lactide), poly(DL-lactide-co-glycolide). poly(DL-lactide-co-ε

-caprolactone), polycaprolactone, and combinations thereof.

21. The method of claim 1, wherein said administering said drug to said portion of said patient'"'"'s body includes depositing said drug intramuscularly.

22. The method of claim 21, wherein said depositing said drug intramuscularly comprises a delivery method selected from the group consisting of:

injection and implantation.

23. The method of claim 21, wherein said depositing said drug intramuscularly comprises depositing a sustained release drug intramuscularly.

24. The method of claim 23, wherein depositing said sustained release drug intramuscularly comprises depositing said drug incorporated in a biodegradable, biocompatible polymer.

25. The method of claim 24, wherein said biodegradable, biocompatible polymer is a polymer of lactic and glycolic acid.

26. The method of claim 24, wherein said biodegradable, biocompatible polymer is a copolymer of lactic and glycolic acid.

27. The method of claim 24, wherein said biodegradable, biocompatible polymer is selected from the group consisting of poly(DL-lactide), poly(DL-lactide-co-glycolide), poly(DL-lactide-co-ε

-caprolactone), polycaprolactone, and combinations thereof.

28. The method of claim 1, wherein said adjusting the temperature of skin proximate said portion of said human body with said temperature modification apparatus comprises heating said skin proximate said portion of said human body.

29. The method of claim 28, wherein said heating said skin proximate said portion of said human body includes heating said skin up to a temperature of about 60°

C.

30. The method of claim 29, wherein said heating said skin proximate said portion of said human body includes heating said skin to a temperature of between about 36 and 46°

C.

31. The method of claim 30, wherein said heating said skin proximate said portion of said human body includes heating said skin to a temperature of between about 37 and 44°

C.

32. The method of claim 28, wherein said heating said portion of said human body effectuates said reduced onset time of said drug through increasing skin permeability for said drug being applied transdermally.

33. The method of claim 32, wherein applying said drug transdermally is effectuated by applying a dermal drug delivery system to the skin of said portion of said human body.

34. The method of claim 28, wherein said heating said portion of said human body is effectuated by applying said temperature modification apparatus to a dermal drug system, including a rate limiting membrane, which is applied to the skin of said portion of said human body;

and wherein said heating said portion of said human body effectuates said reduced onset time of said effect of said drug in said targeted area of said human body by increasing the permeability of said drug through said rate limiting membrane.

35. The method of claim 28, wherein said heating said portion of said human body effectuates said reduced onset time of the effect of said drug in said targeted area of said human body through increasing the permeability of blood vessel walls in sub-skin tissues.

36. The method of claim 28, wherein said heating said portion of said human body effectuates said reduced onset time of the effect of said drug in said targeted area of said human body through increasing the solubility of said drug.

37. The method of claim 28, wherein said heating said portion of said human body effectuates said reduced onset time of the effect of said drug in said targeted area of said human body through increasing circulation of body fluid in tissues proximate said drug.

38. The method of claim 28, wherein said adjusting said temperature of said portion of said human body with said temperature modification apparatus to achieve said reduced onset time of the effect of said drug further achieves a desired concentration of said drug in said targeted area.

39. The method of claim 38, further including removing said temperature modification apparatus after said desired concentration of said drug in said targeted area is achieved.

40. A method of reducing the onset time of a drug in a targeted area of a human body comprising:

administering a drug to a portion of said human body, wherein said administering said drug is a method selected from the group consisting of transdermal application, application of a dermal drug delivery system, subcutaneous administration, and intramuscular administration;

applying an apparatus capable of generating heat proximate said drug being administered, said apparatus capable of generating controlled heat proximate said portion of said human body 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; and

heating skin proximate said portion of said human body to a temperature of between about 38 and 45°

C. with said apparatus to achieve said reduced onset time of said drug.

41. A method of reducing the onset time of an analgesic in a targeted area of a human body comprising:

administering said analgesic into a site of said human body within about 3 centimeters from the surface of the skin proximate said site;

applying a temperature modification apparatus proximate said skin proximate said site, said temperature modification apparatus capable of generating controlled heat proximate said site of said administered analgesic 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; and

heating said skin proximate said site with said temperature modification apparatus to achieve said reduced onset time of said analgesic.

42. The method of claim 41, wherein said analgesic is selected from the drug group consisting of morphine, fentanyl, sufentanil, alfentanil, and meperidine.