Tissue Conforming Microneedle Array and Patch For Transdermal Drug Delivery or Biological Fluid Collection

• US 20080125743A1
• Filed: 11/28/2006
• Published: 05/29/2008
• Est. Priority Date: 11/28/2006
• Status: Active Grant

• Current Assignee: Vadim V. Yuzhakov
• Original Assignee: Vadim V. Yuzhakov
• Inventors: Yuzhakov, Vadim V.
• Granted Patent: US 7,785,301 B2
• Time in Patent Office: Days
• US Class Current: 604/506
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

Microneedle arrays are provided for use on a contoured or flexible tissue surface. In one embodiment, the microneedle array includes a plurality of microneedles, each having a base portion, a tip end portion distal to the base portion, and body portion therebetween; and a flexible substrate which comprises a plurality of apertures, each of which are defined by (i) a plurality of substrate elements which are integral with the base portions of the microneedles, and (ii) at least one spring element connecting at least two of the substrate elements. The spring element may include a curved element, such as a C-shaped, U-shaped, or S-shaped element. Apertures may be defined, for example, by two substrate elements, which connected to three or four spring elements. A skin patch is provided for therapeutic or diagnostic applications, which includes the microneedle array and an adhesive material.

Claims

1. A microneedle array for use on a contoured or flexible tissue surface comprising:

a plurality of microneedles, each having a base portion, a tip end portion distal to the base portion, and body portion therebetween; and

a flexible substrate which comprises a plurality of apertures, each of which are defined by (i) a plurality of substrate elements which are integral with the base portions of the microneedles, and (ii) at least one spring element connecting at least two of the substrate elements.

2. The microneedle array of claim 1, wherein the spring element comprises a curved element.

3. The microneedle array of claim 5, wherein the curved element is C-shaped, U-shaped, or S-shaped.

4. The microneedle array of claim 1, wherein at least one of the apertures is defined by two substrate elements.

5. The microneedle array of claim 1, wherein each substrate element is connected to three or four spring elements.

6. The microneedle array of claim 1, wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate.

7. The microneedle array of claim 6, wherein the base portion of the at least one of the microneedles is untapered and has a substantially rectangular cross-sectional shape in a plane parallel to the substrate.

8. The microneedle array of claim 7, wherein the at least one channel is open to two opposing surfaces of the microneedle.

9. The microneedle array of claim 6, wherein the tip end portion of the at least one of the microneedles is tapered.

10. The microneedle array of claim 9, wherein the at least one channel extends into the tapered tip portion.

11. The microneedle array of claim 1, wherein the flexible substrate and the microneedles are formed of a biocompatible metal or polymer.

12. The microneedle array of claim 11, wherein the biocompatible metal comprises a stainless steel.

13. The microneedle array of claim 1, wherein the length of the plurality of microneedles is between 100 μ

m and 500 μ

m.

14. A device for transdermal administration of a drug, comprising:

the microneedle array of claim 1; and

at least one drug storage element, which contains a drug formulation, disposed adjacent to the microneedle array.

15. The device of claim 14, wherein the drug storage element is attached to a first surface of the substrate, the first surface being opposed to a second surface of the substrate of the microneedle array, wherein the microneedles project from said second surface.

16. The device of claim 14, wherein the drug storage element is coated onto an outer surface of the microneedles.

17. The device of claim 14, wherein the drug storage element can flex and deform with substrate of the microneedle array.

18. The device of claim 14, further comprising a release mechanism for releasing the drug formulation from the drug storage element to permit the drug formulation to pass through the apertures of the substrate of the microneedle array.

19. The device of claim 14, wherein the drug storage element comprises a porous material, wherein the drug formulation is stored in pores of the porous material.

20. The device of claim 14, further comprising an adhesive surface suitable for securing the device to the skin of a patient during administration of the drug formulation to the patient.

21. The device of claim 14, further comprising a removable release liner, which covers the microneedles and apertures prior to use of the device.

22. A device for transdermal sampling of a biological fluid, comprising:

the microneedle array of claim 1; and

at least one collection reservoir for retaining a biological fluid sample drawn through the microneedle array.

23. The device of claim 22, further comprising a sensor for testing biological fluid retained in the collection reservoir.

28. A method of administering a drug to a patient in need thereof, comprising:

inserting into the skin of the patient the microneedles of the microneedle array of claim 1, to form holes in the stratum corneum; and

causing a fluid drug formulation to be transported through the apertures of the substrate of the microneedle array and then through the holes in the stratum corneum, while the microneedles remain positioned in the holes.

29. The method of claim 28, wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate.

30. A method of transdermally collecting a biological fluid sample from a patient, comprising:

inserting into the skin of the patient the microneedles of the device of claim 1, to form holes in the stratum corneum; and

causing the biological fluid to be withdrawn from the patient through the holes in the stratum corneum and then through the apertures of the substrate of the microneedle array, while the microneedles remain positioned in the holes.

31. The method of claim 30, wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate.

24. A method for manufacturing a microneedle array comprising:

(a) forming a flexible substrate which comprises a plurality of apertures, each of which are defined by (i) a plurality of substrate elements, and (ii) at least one spring element connecting at least two of the substrate elements; and

(b) forming a plurality of microneedles, each having a base portion, a tip end portion distal to the base portion, and body portion therebetween, wherein the base portions of the microneedles are integral with the substrate elements.

25. The method of claim 24, which comprises forming in a planar substrate material the plurality of apertures, the plurality of substrate elements, and the plurality of spring elements, by removing selected portions of the substrate material.

26. The method of claim 24, wherein the removal process comprises embossing, injection molding, casting, photochemical etching, electrochemical machining, electrical discharge machining, precision stamping, high-speed computer numerically controlled milling, Swiss screw machining, soft lithography, directional chemically assisted ion etching, laser cutting, or a combination thereof.

27. The method of claim 24, wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate.

32. A skin patch for therapeutic or diagnostic applications comprising:

a microneedle array which comprises

a plurality of microneedles, each having (i) a base portion, a tip end portion distal to the base portion, and body portion therebetween, and (ii) a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion;

a flexible substrate which comprises a plurality of apertures, each of the apertures being defined by (i) two or more substrate elements which are integral with the base portions of the microneedles, and (ii) at least two spring elements connected to the two or more substrate elements, wherein the channels of the microneedles are in fluid communication with at least one of the apertures in the substrate; and

an adhesive material for securing the microneedle array to a patient'"'"'s skin with the microneedles inserted into the stratum corneum.

33. The skin patch of claim 32, wherein the spring element comprises a curved element.

34. The skin patch of claim 33, wherein the curved element is C-shaped, U-shaped, or S-shaped.

35. The skin patch of claim 32, wherein each substrate element is connected to three or four spring elements.

36. The skin patch of claim 32, wherein the base portion of the at least one of the microneedles is untapered and has a substantially rectangular cross-sectional shape in a plane parallel to the substrate.

37. The skin patch of claim 36, wherein the at least one channel is open to two opposing surfaces of the microneedle.

38. The skin patch of claim 32, wherein the tip end portions of the microneedles are tapered.

39. The skin patch of claim 38, wherein the at least one channel extends into the tapered tip end portion.

40. The skin patch of claim 32, wherein the flexible substrate and the microneedles are formed of a biocompatible metal.

41. The skin patch of claim 32, wherein the flexible substrate and the microneedles are formed of a biocompatible polymer.

42. The skin patch of claim 32, further comprising a drug storage element for releasing a drug formulation to the patient'"'"'s skin.