Photokinetic delivery of biologically active substances using pulsed incoherent light

• US 7,458,982 B2
• Filed: 10/03/2003
• Issued: 12/02/2008
• Est. Priority Date: 10/04/2002
• Status: Active Grant

• Current Assignee: Photokinetix, Inc.
• Original Assignee: Photokinetix, Inc.
• Inventors: Kraft, Edward R., Kulp, Gabriela
• Primary Examiner(s): Desai; Anand U
• Application Number:
  US10/679,112
• Publication Number:
  US 20040131687A1
• Time in Patent Office: 1,887 Days
• Field of Search: None
• US Class Current: 607/88
• CPC Class Codes: A61K 41/0042 Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00

Abstract

The invention relates generally to transdermal and transmembrane delivery of biologically active substances through the skin, sub-dermal tissues, blood vessels and cellular membranes without causing damage to the cellular surface, tissue or membrane. The invention provides compositions and methods for enhanced transdermal and transmembrane delivery of biologically active substances using pulsed incoherent light. The invention further provides a device for the application of the pulsed incoherent light to cellular surfaces and membranes using those compositions and methods.

Claims

1. A method of photokinetic transdermal delivery of a biologically active substance comprising:

preparing a solution comprising the biologically active substance and a solvent;

applying said solution to a cellular surface on the skin;

illuminating said solution on said cellular surface with a pulsed incoherent light having a selected wavelength, pulse rate and duty cycle; and

allowing said solution to permeate said cellular surface.

2. The method according to claim 1 wherein said solution further comprises a gelling agent.

3. The method according to claim 1 wherein said solution further compnses a photocatalytic agent.

4. The method according to claim 1 wherein said biologically active substance comprises a drug.

5. The method according to claim 1 wherein said biologically active substance comprises chemicals and said chemicals comprise a polar or a non-polar compound.

6. The method according to claim 5 wherein said polar compound is selected from the group consisting of theophylline-7 acetic acid, sodium ascorbyl phosphate, ascorbic acid, ascorbyl palmitate, pyridoxine, nicotinic acid, and lidocaine.

7. The method according to claim 5 wherein said non-polar compound is selected from the group consisting of theobromine, theophylline, caffeine, and nicotinamide.

8. The method according to claim 4 wherein said drug is a cytotoxic drug.

9. The method according to claim 1 wherein said biologically active substance comprises a peptide and said peptide is selected from the group consisting of Gly-Tyr, Val-Tyr-Val, Tyr-Gly-Gly-Phe-Met (SEQ ID NO:

1), Tyr-Gly-Gly-Phe-Leu (SEQ ID NO;

     2), and Asp-Arg-Val-Tyr-Ile-His-Pro-Phe (SEQ ID NO;

     3).

10. The method according to claim 1 wherein said biologically active substance comprises a hormone and said hormone is selected from the group consisting of methionine enkephalin acetate, leucine enkephalin, angiotensin II acetate, β

-estradiol, methyl testosterone, and progesterone.

11. The method according to claim 1 wherein said biologically active substance comprises a protein and said protein is selected from the group consisting of enzymes, non-enzymes, antibodies, and glycoproteins.

12. The method according to claim 2 wherein said gelling agent comprises a cellulose derivative.

13. The method according to claim 3 wherein said photocatalytic agent has a band gap energy of between about 2.9 eV and about 3.2 eV.

14. The method according to claim 3 wherein said photocatalytic agent is a rutile form of titanium dioxide.

15. The method according to claim 3 wherein said photocatalytic agent is an anatase form of titanium dioxide.

16. The method according to claim 1 wherein said solvent is an aqueous or an organic solvent.

17. The method according to claim 16 wherein said aqueous solvent is water.

18. The method according to claim 16 wherein said aqueous solvent is an aqueous solution of ethyl lactate or propylene glycol.

19. The method according to claim 1 wherein said cellular surface is a cell membrane.

20. The method according to claim 1 wherein said pulsed incoherent light is selected from the group consisting of fluorescent, ultraviolet, visible, near infrared, LED (light emitting diode), and halogen light.

21. The method according to claim 20 wherein said fluorescent light has a wavelength range from about 260 nm to about 760 nm.

22. The method according to claim 20 wherein said ultraviolet light has a wavelength range from about 340 nm to about 900 mm.

23. The method according to claim 20 wherein said visible light has a wavelength range from about 340 nm to about 900 nm.

24. The method according to claim 20 wherein said near infrared light has a wavelength range from about 340 nm to about 900 nm.

25. The method according to claim 20 wherein said halogen light has a wavelength range from about 340 nm to about 900 nm.

26. The method according to claim 1 wherein said wavelength is selected from the group consisting of 350 nm, 390 nm, 405 nm, and 450 nm.

27. The method according to claim 1 wherein said pulse rate is between about 1.7 cycles per second (cps) and about 120 cps.

28. The method according to claim 27 wherein said pulse rate is between about 1.7 cps and about 80 cps.

29. The method according to claim 1 wherein said duty cycle is between about 50% and about 75%.

30. The method according to claim 1 wherein said biologically active substance comprises a chemical.

31. The method according to claim 1 wherein said biologically active substance comprises an antibiotic.

32. The method according to claim 1 wherein said biologically active substance comprises a hormone.

33. The method according to claim 4 wherein said drug comprises an analgesic.

34. The method according to claim 4 wherein said drug comprises an anaesthetic.

35. The method according to claim 4 wherein said drug comprises an antacid.

36. The method according to claim 4 wherein said drug comprises an antianxiety drugs.

37. The method according to claim 4 wherein said drug comprises an antiarrhythmics.

38. The method according to claim 4 wherein said drug comprises an antibacterial.

39. The method according to claim 4 wherein said drug comprises an antibiotic.

40. The method according to claim 4 wherein said drug comprises an anticoagulant and thrombolytic.

41. The method according to claim 4 wherein said drug comprises an anticonvulsants.

42. The method according to claim 4 wherein said drug comprises an antidiarrheals.

43. The method according to claim 4 wherein said drug comprises an antiviral.

44. The method according to claim 4 wherein said drug comprises a barbiturates.

45. The method according to claim 4 wherein said drug comprises a vitamin.

46. The method according to claim 2 wherein said gelling agent comprises a hydroxyethyl cellulose.

47. The method according to claim 2, wherein said gelling agent comprises a pectines.

48. The method according to claim 2, wherein said gelling agent comprises an agar.

49. The method according to claim 2, wherein said gelling agent comprises an alginic acid and its salts.

50. The method according to claim 2, wherein said gelling agent comprises a guar gum.

51. The method according to claim 2, wherein said gelling agent comprises a polyvinyl alcohol.

52. The method according to claim 2, wherein said gelling agent comprises a polyethylene oxide.

53. The method according to claim 2, wherein said gelling agent comprises a propylene carbonate.

54. The method according to claim 2, wherein said gelling agent comprises a polyethylene glycol.

55. The method according to claim 2, wherein said gelling agent comprises a hexylene glycol sodium carboxymethylcellulose.

56. The method according to claim 2, wherein said gelling agent comprises a polyacrylates.

57. The method according to claim 2, wherein said gelling agent comprises a polyoxyethylene-polyoxypropylene.

58. The method according to claim 2, wherein said gelling agent comprises block copolymers.

59. The method according to claim 2, wherein said gelling agent comprises a pluronics.

60. The method according to claim 2, wherein said gelling agent comprises a wood wax alcohol.

61. The method according to claim 2, wherein said gelling agent comprises a tyloxapol.

62. The method according to claim 1, wherein said biologically active substance comprises a peptide.

63. The method according to claim 1 wherein said biologically active substance is selected from the group consisting of a drug, a chemical, an antibody, a peptide, a hormone, a protein, and a mixture thereof.

64. The method according to claim 16 wherein said aqueous solvent is an aqueous solution of ethyl lactate and proplyene glycol.