Intradermal delivery of substances

• US 20040073160A1
• Filed: 06/29/2001
• Published: 04/15/2004
• Est. Priority Date: 06/29/2000
• Status: Abandoned Application

• Current Assignee: Pharmacia Corporation (Pfizer Inc.)
• Original Assignee: Pharmacia Corporation (Pfizer Inc.)
• Inventors: Pinkerton, Thomas C.
• Application Number:
  US09/897,753
• Publication Number:
  US 20040073160A1
• Time in Patent Office: Days
• US Class Current: 604/28
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61M 2037/0038 having a channel at the side surface
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 5/158 Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
• CPC Class Codes: A61M 5/32 Needles; Details of needles pertaining to their connection with syringe or hub infusion needles A61M5/158; Accessories for bringing the needle into, or holding the needle on, the body A61M5/42, A61M5/46 take precedence; guide needles for catheters A61M25/065; Devices for protection of needles apparatus specially adapted for cleaning or sterilising needles A61M5/001
• CPC Class Codes: A61M 5/3286 Needle tip design, e.g. for improved penetration
• CPC Class Codes: A61M 5/3291 Shafts with additional lateral openings
• CPC Class Codes: A61M 5/3295 Multiple needle devices, e.g. a plurality of needles arranged coaxially or in parallel
• CPC Class Codes: A61M 5/46 having means for controlling depth of insertion
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

A method for administration of a substance into the dermis of a mammal is disclosed. The method involves administration into the dermis by injection which results in improved systemic absorption relative to that obtained upon subcutaneous administration of the substance. The substance administered may be a growth hormone, a low molecular weight heparin or a dopamine receptor agonist.

Claims

24. A method of administering a pharmaceutical substance comprising injecting the substance intradermally through one or more microneedles having a length and outlet suitable for selectively delivering the substance into the dermis to obtain absorption of the substance in the dermis.

25. The method of claim 24 wherein absorption of the substance in the dermis produces improved systemic pharmacokinetics compared to subcutaneous administration.

26. The method of claim 25 wherein the improved pharmacokinetics is increased bioavailability.

27. The method of claim 25 wherein the improved pharmacokinetics is decreased T_max.

28. The method of claim 25 wherein the improved pharmacokinetics is an increase in C_max.

29. The method of claim 25 wherein the improved pharmacokinetics is a decrease in T_lag.

30. The method of claim 25 wherein the improved pharmacokinetics is an enhanced absorption rate.

31. The method of claim 24 wherein the length of the microneedle is from about 0.5 mm to about 1.7 mm.

32. The method of claim 24 wherein the microneedle is a 30 to 34 gauge needle

33. The method of claim 24 wherein the microneedle has an outlet of from 0 to 1 mm.

34. The method of claim 24 wherein the microneedle is configured in a delivery device which positions the microneedle perpendicular to skin surface.

35. The method of claim 24 wherein the microneedle needle is contained in an array of microneedles needles.

36. The method of claim 35 wherein the array comprises 3 microneedles.

37. The method of claim 35 wherein the array comprises 6 microneedles.

38. A microneedle for intradermal injection of a pharmaceutical substance, wherein the microneedle has a length and outlet selected for its suitability for specifically delivering the substance into the dermis.

39. The microneedle according to claim 38 wherein the length of the microneedle is from about 0.5 mm to about 1.7 mm.

40. The microneedle of claim 38 which is a 30 to 34 gauge needle

41. The microneedle of claim 38 which has an outlet of from 0 to 1 mm

42. The microneedle of claim 38 which is configured in a delivery device which positions the microneedle perpendicular to skin surface.

43. The microneedle of claim 42 which is in an array of microneedles needles.

44. The microneedle of claim 43 wherein the array comprises 3 microneedles.

45. The microneedle of claim 43 wherein the array comprises 6 microneedles.

46. A method for delivering a bioactive substance to a subject comprising:

contacting the skin of the subject with a device having a dermal-access means for accurately targeting the dermal space of the subject with an efficacious amount of the bioactive substance.

1. A method for directly delivering a substance into an intradermal space within mammalian skin comprising administering the substance through at least one small gauge hollow needle having an outlet with an exposed height between 0 and 1 mm, said outlet being inserted into the skin to a depth of between 0.3 mm and 2 mm, such that delivery of the substance occurs at a depth between 0.3 mm and 2 mm.

2. The method according to claim 1 wherein the delivered substance has improved pharmacokinetics compared to pharmacokinetics after subcutaneous injection.

3. The method of claim 1 wherein the injecting is through at least one small gauge hollow needle.

4. The method of claim 1 wherein the needle has an outlet with an exposed height between 0 and 1 mm.

5. The method of claim 1 wherein injecting comprises inserting the needle to a depth which delivers the substance at least about 0.3 mm below the surface to no more than about 2 mm below the surface.

6. The method of claim 1 wherein administering comprises inserting the needle into the skin to a depth of at least about 0.3 mm and no more than about 2 mm.

7. The method of claim 2 wherein the improved pharmacokinetics is increased bioavailability of the substance.

8. The method of claim 2 wherein the improved pharmacokinetics is a decrease in T_max.

9. The method of claim 2 wherein the improved pharmacokinetics is an increase in C_max.

10. The method of claim 2 wherein the improved pharmacokinetics is a decrease in T_lag.

11. The method of claim 2 wherein the improved pharmacokinetics is enhanced absorption rate.

12. The method of claim 1 wherein the substance is administered over a time period of not more than ten minutes.

13. The method of claim 1 wherein the substance is administered over a time period of greater than ten minutes.

14. The method of claim 1 wherein the substance is a protein.

15. The method of claim 1 wherein the substance is administered at a rate between 1 nL/min. and 200 mL/ min.

16. The method of claim 1 wherein said substance is a hormone.

17. The method of claim 16 wherein said hormone is selected from the group consisting of insulin and PTH.

18. The method of claim 1 wherein said substance is a nucleic acid.

19. The method of claim 1 wherein the substance has a molecular weight of less than 1000 daltons.

20. The method of claim 1 wherein the substance has a molecular weight greater than 1000 daltons.

21. The method of claim 1 wherein said substance is hydrophobic.

22. The method of claim 1 wherein said substance is hydrophilic.

23. The method of claim 1 wherein the needle(s) are inserted perpendicularly to the skin.

47. The method of claim 46 wherein the pharmacokinetics of the bioactive substance is improved relative to the pharmacokinetics of the substance when administered subcutaneously.

48. The method of claim 47 wherein the improved pharnacokinetics is an increase in bioavailability.

49. The method of claim 47 wherein the improved pharmacokinetics is a decrease

50. The method of claim 47 wherein the improved pharmacokinetics comprises an increase in C_max of the substance compared to subcutaneous injection.

51. The method of claim 47 wherein the improved pharmacokinetics is a decrease in T_lag.

52. The method of claim 47 wherein the improved pharmacokinetics is an enhanced absorption rate.

53. The method of claim 46 wherein the device has a fluid driving means including a syringe, infusion pump, piezoelectric pump, electromotive pump, electromagnetic pump, or Belleville spring.

54. The method of claim 46 wherein said dermal access means comprises one or more hollow microcannula having an outlet with an exposed height between 0 and 1 mm.

53-1. The method of claim 46 wherein the dermal access means comprises one or more hollow microcannula having a length of from about 0.5 to about 1.7 mm-mm.

55. A method for delivering a bioactive substance to a subject comprising:

contacting the skin of a subject with a device having a dermal-access means for accurately targeting the dermal space of the subject with an efficacious amount of the bioactive substance at a rate of 1 nL/min. to 200 mL/min.

56. The method of claim 55 wherein the rapid onset pharmacokinetics of the bioactive substance is substantially improved relative to subcutaneous injection.

57. The method of claim 56 wherein the bioavailability is increased.

58. The method of claim 56 wherein the pharmokinetics is a decreased T_max.

59. The method of claim 56 wherein the pharmokinetics is an increased C_max.

60. The method of claim 56 wherein the pharmokinetics is a decreased T_lag.

61. The method of claim 56 wherein the pharmokinetics is an enhanced absorption rate.

62. The method of claim 55 wherein the dermal access means has one or more hollow microcannula that inserts into the skin of said subject to a depth of from about 0.5 to about −

2.0 mm.

63. The method of claim 55 wherein the dermal access means has one or more hollow microcannula having an outlet with an exposed height between 0 and 1 mm.