Intradermal delivery of substances

• US 8,998,877 B2
• Filed: 04/19/2013
• Issued: 04/07/2015
• Est. Priority Date: 06/29/2000
• Status: Expired due to Fees

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Pettis, Ronald J., Down, James A., Harvey, Noel G.
• Primary Examiner(s): Sirmons, Kevin C
• Assistant Examiner(s): GRAY, PHILLIP A
• Application Number:
  US13/866,446
• Publication Number:
  US 20130237961A1
• Time in Patent Office: 718 Days
• Field of Search: 604/117, 604/21, 604272-274, 604500-522, 6048901-8921
• US Class Current: 604/503
• 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

The present invention provides improved methods for ID delivery of drugs and other substances to humans or animals. The methods employ small gauge needles, especially microneedles, placed in the intradermal space to deliver the substance to the intradermal space as a bolus or by infusion. It has been discovered that the placement of the needle outlet within the skin and the exposed height of the needle outlet are critical for efficacious delivery of active substances via small gauge needles to prevent leakage of the substance out of the skin and to improve absorption within the intradermal space. The pharmacokinetics of hormone drugs delivered according to the methods of the invention have been found to be very similar to the pharmacokinetics of conventional SC delivery, indicating that ID administration according to the methods of the invention is likely to produce a similar clinical result (i.e., similar efficacy) with the advantage of reduction or elimination of pain for the patient. Delivery devices which place the needle outlet at an appropriate depth in the intradermal space and control the volume and rate of fluid delivery provide accurate delivery of the substance to the desired location without leakage.

Claims

1. A method for administration of a drug to a human subject, comprising delivering the drug through the lumen of a hollow needle into an intradermal compartment of the human subject'"'"'s skin, which method comprises

(a) inserting the needle into the subject'"'"'s skin so that the needle penetrates the intradermal compartment, and the needle'"'"'s outlet depth and exposed height of the outlet are located within the intradermal compartment, wherein the outlet has an exposed height of about 0 to 1 mm;

and

(b) delivering the drug through the lumen of the needle with the application of pressure in an amount effective to control the rate of delivery of the drug,

so that the drug is delivered through the lumen of the needle into the intradermal compartment and distributed systemically exhibiting any one of the following improved pharmacokinetic parameters as compared to subcutaneous delivery;

(i) a higher maximum plasma concentration and a faster onset of a detectable plasma level;

(ii) a higher maximum plasma concentration and a higher bioavailability;

or

(iii) a faster onset of a detectable plasma level and a higher bioavailability.

2. The method of claim 1, wherein the improved pharmacokinetic parameters are a higher maximum plasma concentration and a faster onset of a detectable plasma level.

3. The method of claim 1, wherein the improved pharmacokinetic parameters are a higher maximum plasma concentration and a higher bioavailability.

4. The method of claim 1, wherein the improved pharmacokinetic parameters are a faster onset of a detectable plasma level and a higher bioavailability.

5. The method of claim 1, wherein the needle is selected from the group consisting of microneedles, catheter needles, and injection needles.

6. The method of claim 1, wherein a single needle is inserted.

7. The method of claim 1, wherein multiple needles are inserted.

8. The method of claim 1, wherein the needle is about 300 μ

m to 2 mm long.

9. The method of claim 1, wherein the needle is about 500 μ

m to 1 mm long.

10. The method of claim 1, wherein the outlet is at a depth of about 250 μ

m to 2 mm when the needle is inserted.

11. The method of claim 1, wherein the outlet is at a depth of about 750 μ

m to 1.5 mm when the needle is inserted.

12. The method of claim 1, wherein the outlet has an exposed height of about 0 to 300 μ

m.

13. The method of claim 1, wherein the delivery rate or volume is controlled by spacing of multiple needles, needle diameter or number of needles.

14. The method of claim 1, wherein the drug is a hormone, antitoxin, pain medication, thrombolytic, or antiinfective.

15. The method of claim 14, wherein the hormone is PTH or growth hormone.

16. The method of claim 14, wherein the pain medication is a triptan, opioid, analgesic, or anesthetic.

17. The method of claim 14, wherein the thrombolytic is heparin or warfarin.

18. The method of claim 14, wherein the antiinfective is an antibiotic.