Devices and methods for enhanced microneedle penetration of biological barriers

• US 20050137531A1
• Filed: 05/28/2004
• Published: 06/23/2005
• Est. Priority Date: 11/23/1999
• Status: Abandoned Application

• Current Assignee: Georgia Tech Research Corporation (University System of Georgia), Valeritas, LLC
• Original Assignee: Valeritas, LLC
• Inventors: Henry, Sebastian, Ackley, Donald E., Prausnitz, Mark R., Jackson, Thomas, Allen, Mark G., McAllister, Devin V.
• Application Number:
  US10/856,691
• Publication Number:
  US 20050137531A1
• Time in Patent Office: Days
• US Class Current: 604/173
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150068 by tissue compression, e.g. with specially designed surface of device contacting the skin area to be pierced
• CPC Class Codes: A61B 5/150076 by heating
• CPC Class Codes: A61B 5/150083 by vibration, e.g. ultrasound
• CPC Class Codes: A61B 5/150099 by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
• CPC Class Codes: A61B 5/150213 Venting means
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150412 Pointed piercing elements, e.g. needles, lancets for piercing the skin blade-like piercing elements A61B5/150442
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/151 Devices specially adapted for taking samples of capillary blood, e.g. by lancets , needles or blades
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 5/422 Desensitising skin
• CPC Class Codes: A61M 5/425 : Protruding skin to facilitate piercing, e.g. vacuum cylinders, vein immobilising means
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing

Abstract

Microneedle devices and methods of use thereof are provided for the enhanced transport of molecules, including drugs and biological molecules, across tissue by improving the interaction of microneedles and a deformable, elastic biological barrier, such as human skin. The devices and methods act to (1) limit the elasticity, (2) adapt to the elasticity, (3) utilize alternate ways of creating the holes for the microneedles to penetrate the biological barrier, other than the simply direct pressure of the microneedle substrate to the barrier surface, or (4) any combination of these methods. In preferred embodiments for limiting the elasticity of skin, the microneedle device includes features suitable for stretching, pulling, or pinching the skin to present a more rigid, less deformable, surface in the area to which the microneedles are applied (i.e. penetrate). In a preferred embodiments for adapting the device to the elasticity of skin, the device comprising one or more extensions interposed between the substrate and the base end of at least a portion of the microneedles.

Claims

1. A device for transport of material or energy across or into an elastic biological barrier comprising:

a microneedle having a tip end and a base end,

a substrate connected to the base end of the microneedle, and

a means for improving penetration of the biological barrier by the microneedle.

2. The device of claim 1 wherein the biological barrier is human or other mammalian skin.

3. The device of claim 1 wherein the means comprises one or more extensions

(i) interposed between the substrate and the base end of the microneedle, or

(ii) extending from the side of the substrate distal to the base end of the microneedle.

4. The device of claim 3 wherein the extension is between about 500 μ

m and about 10 mm in height.

5. The device of claim 3 wherein the extension has a cross-sectional dimension of at least about 200 μ

m.

6. The device of claim 3 wherein the extension includes an array of microneedles extending therefrom.

7. The device of claim 3 wherein the extension is composed of a material which is different from the material forming the microneedles.

8. The device of claim 3 wherein the microneedle is hollow and wherein the extension includes at least one aperture in communication with the bore of the microneedle.

9. The device of claim 3 further comprising a rigid surface positioned apart from an array of the microneedles and oriented to contact an elastic biological barrier substantially at the same time as the microneedles when the microneedles are applied to the barrier.

10. The device of claim 1 wherein the substrate is curved.

11. The device of claim 1 comprising a plurality of microneedles of varying lengths.

12. The device of claim 11 comprising four or more microneedles wherein the tip ends of the microneedles collectively define a curvilinear surface.

13. The device of claim 1 comprising a plurality of hollow microneedles in a linear array, wherein the substrate is mounted on a holder having one or more apertures through the holder in communication with the microneedles.

14. The device of claim 1 wherein the substrate is flexible.

15. The device of claim 14 wherein the substrate is deformable by fluid pressure or mechanical means.

16. The device of claim 15 wherein the substrate is mounted onto a flexible membrane bubble.

17. The device of claim 16 further comprising a second membrane bubble positioned to define a chamber between the flexible membrane bubble and the second membrane bubble.

18. The device of claim 17 wherein the chamber contains molecules which flow through the microneedle.

19. The device of claim 18 wherein the molecules are drug molecules.

20. The device of claim 1 wherein the means reduces the elasticity of the biological barrier.

21. The device of claim 20 wherein the means physically manipulates the biological barrier to present a more rigid surface in the area of the biological barrier to be penetrated by the microneedle.

22. The device of claim 21 wherein the manipulation is selected from the group consisting of stretching, pulling, pinching, and a combination thereof.

23. The device of claim 22 wherein the manipulation includes pulling by reducing the atmospheric pressure over the area of the biological barrier to be penetrated by the microneedles.

24. The device of claim 23 further comprising a body portion defining a first vacuum region and a second vacuum region, wherein an array of microneedles separates the first and second regions.

25. The device of claim 24 wherein the body portion comprises an annular ring which holds the microneedles.

26. The device of claim 25 wherein the microneedle is hollow and wherein the body portion further comprises a means for attachment to a syringe, a conduit for connection to a vacuum pump, or both.

27. The device of claim 22 wherein the means comprises a stretching cone or expandable ring around the microneedles.

28. The device of claim 22 wherein the means comprises a body portion from which a plurality of stretching elements are pivotally attached.

29. The device of claim 28 wherein the stretching elements have ends provided with a non-slip feature for engagement with the biological barrier.

30. The device of claim 22 wherein the means comprises jaws for pinching a portion of the biological barrier for contact with the microneedles.

31. The device of claim 21 wherein the means comprises an adhesive film applied over the area of the biological barrier to be penetrated by the microneedle.

32. The device of claim 2 wherein the means for improving penetration creates holes in the stratum corneum, wherein the microneedle can be inserted into the holes.

33. The device of claim 32 wherein the means for creating holes is selected from the group consisting of thermal ablation, high pressure fluid puncturing, cryoablation, and application of degradation agents.

34. The device of claim 1 wherein the means for improving penetration accelerates the tips of the microneedles into the biological barrier, accelerates the biological barrier into contact with the tips of the microneedles, or a combination thereof.

35. The device of claim 34 wherein the means for accelerating the tip of the microneedle comprises releasing a spring or gas under compression.

36. The device of claim 1 wherein a lubricating material is incorporated into or coated onto the microneedle.

37. The device of claim 1 further comprising a collar to limit the depth of microneedle penetration.

38. The device of claim 1 further comprising a means for attaching the device to the skin of a patient, wherein the means is not the microneedle.

39. The device of claim 38 wherein the means is an adhesive film.

40. The device of claim 38 wherein the means is an arm band.

41. The device of claim 1 wherein the microneedle is hollow and wherein the device further comprises a reservoir selectably in communication with the hollow microneedle.

42. The device of claim 1 wherein the means for enhancing penetration comprises an apparatus for vibrating the microneedle.

43. The device of claim 42 wherein the apparatus comprises a piezoelectric transducer or an electromechanical actuator.

45. A method for transport of material or energy across or into an elastic biological barrier, comprising using the device of claim 1.

44. A kit of parts for use in transport of material or energy across or into an elastic biological barrier, comprising

(i) a device comprising one or more microneedles having a tip end and a base end, and a substrate connected to the base end of the microneedle, and

(ii) an adhesive film or barrier-tightening chemical, either of which can be applied over an area of the biological barrier to be penetrated by the microneedle.