Method of manufacturing an intracutaneous microneedle array

• US 6,451,240 B1
• Filed: 05/26/2000
• Issued: 09/17/2002
• Est. Priority Date: 06/09/1999
• Status: Expired due to Term

• Current Assignee: Corium, Inc.
• Original Assignee: The Procter & Gamble Company
• Inventors: Gartstein, Vladimir, Sherman, Faiz Feisal, Owens, Grover David, Yuzhakov, Vadim Vladimirovich
• Primary Examiner(s): TENTONI, LEO B
• Application Number:
  US09/579,798
• Time in Patent Office: 844 Days
• Field of Search: 264/154, 264/219, 264/322, 264/504, 427/537, 205/70, 205/164, 205/210, 216/11, 216/41, 216/67, 216/75, 430/320
• US Class Current: 264/504
• 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 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B26F 1/24 Perforating by needles or pins
• CPC Class Codes: B29C 2059/023 Microembossing
• CPC Class Codes: B29C 33/0033 constructed for making articles provided with holes
• CPC Class Codes: B29C 33/42 characterised by the shape of the moulding surface, e.g. ribs or grooves
• CPC Class Codes: B29C 37/0053 Moulding articles characterised by the shape of the surface, e.g. ribs, high polish mould construction therefor B29C33/42; surface shaping of articles B29C59/00; by incorporating filler in or near the surface B29C70/64
• CPC Class Codes: B29C 45/2628 with mould parts forming holes in or through the moulded article, e.g. for bearing cages
• CPC Class Codes: B29C 51/00 Shaping by thermoforming , i.e. shaping sheets or sheet like preforms after heating, e.g. shaping sheets in matched moulds or by deep-drawing; Apparatus therefor blow moulding of tubular preforms B29C49/00, deforming of tubular or hollow preforms B29C67/0014
• CPC Class Codes: B29C 51/082 by shaping between complementary mould parts
• CPC Class Codes: B29L 2031/7544 Injection needles, syringes
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles
• CPC Class Codes: B81B 2201/055 Microneedles
• CPC Class Codes: B81C 1/00111 Tips, pillars, i.e. raised structures microneedles A61M37/0015
• CPC Class Codes: B81C 2201/036 Hot embossing

Abstract

A microneedle array is manufactured using a mold preparation procedure that begins by placing an optical mask over a layer of PMMA material, exposing the PMMA material to x-rays, then developing using a photoresist process. The remaining PMMA material is then electroplated with metal. Once the metal has reached an appropriate thickness, it is detached to become a metal mold that is used in a microembossing procedure, in which the metal mold is pressed against a heated layer of plastic material. Once the mold is pressed down to its proper distance, the plastic material is cooled until solidified, and the mold is then detached, thereby leaving behind an array of microneedles.

Claims

1. A method of preparing a mold for manufacturing a microneedle array, comprising:

providing a photoresist material, in contact with a temporary substrate;

placing a mask layer upon said photoresist material, said mask layer having a predetermined pattern, at least a portion of said mask layer comprising a material that prevents high energy radiation from passing therethrough;

exposing said combination photoresist material/mask layer to high energy radiation;

removing said mask layer, and chemically developing exposed portions of said photo-resist material, thereby removing portions of the photoresist material and leaving behind a pattern of said photoresist material that represents a three-dimensional structure emulating a plurality of microneedles that are to be later formed;

electroplating said patterned photoresist material with a metallic substance; and

detaching said metallic substance from said patterned photoresist material, said metallic substance thereby forming a microneedle array mold;

wherein said mask layer comprises gold.

2. The method as recited in claim 1, wherein said electroplating metallic substance comprises nickel.

3. A method of preparing a mold for manufacturing a microneedle array, comprising:

providing a photoresist material, in contact with a temporary substrate;

placing a mask layer upon said photoresist material, said mask layer having a predetermined pattern, at least a portion of said mask layer comprising a material that prevents high energy radiation from passing therethrough;

exposing said combination photoresist material/mask layer to high energy radiation;

removing said mask layer, and chemically developing exposed portions of said photo-resist material, thereby removing portions of the photoresist material and leaving behind a pattern of said photoresist material that represents a three-dimensional structure emulating a plurality of microneedles that are to be later formed;

electroplating said patterned photoresist material with a metallic substance; and

detaching said metallic substance from said patterned photoresist material, said metallic substance thereby forming a microneedle array mold;

wherein said patterned photoresist material is chemically coated before the step of electroplating to aid in later detachment of the metallic substance from the patterned photoresist material.

4. A method of preparing a mold for manufacturing a microneedle array, comprising:

providing a photoresist material, in contact with a temporary substrate;

placing a mask layer upon said photoresist material, said mask layer having a predetermined pattern, at least a portion of said mask layer comprising a material that prevents high energy radiation from passing therethrough;

exposing said combination photoresist material/mask layer to high energy radiation;

removing said mask layer, and chemically developing exposed portions of said photo-resist material, thereby removing portions of the photoresist material and leaving behind a pattern of said photoresist material that represents a three-dimensional structure emulating a plurality of microneedles that are to be later formed;

electroplating said patterned photoresist material with a metallic substance; and

detaching said metallic substance from said patterned photoresist material, said metallic substance thereby forming a microneedle array mold;

wherein said method of preparing a mold for manufacturing a microneedle array further comprises a microembossing procedure, comprising;

placing a plastic material upon a temperature-controlled surface and, by use of said temperature-controlled surface, heating said plastic material to substantially its elastic working temperature, said plastic material having a first substantially planar surface touching said temperature-controlled surface and a second substantially planar surface on its opposite side;

pressing said microneedle array mold against the second substantially planar surface of said plastic material, thereby forming a three-dimensional pattern comprising a microneedle array in said plastic material;

by use of said temperature-controlled surface, cooling said patterned plastic material below its deformable temperature; and

de-molding, by removing said microneedle array mold from contact with said patterned plastic material, thereby leaving behind a plastic microneedle array.

5. The method as recited in claim 4, wherein said plastic material comprises a biocompatible polymer.

6. The method as recited in claim 4, further comprising:

providing a vacuum during the molding process.

7. The method as recited in claim 4, further comprising:

forming a fluid-holding chamber on the second substantially planar surface side of said patterned microneedle array.

8. A method of manufacturing a microneedle array, comprising:

providing a microneedle array mold;

providing a temperature-controlled mold chamber;

providing a heated plastic material into said temperature-controlled mold chamber having its temperature raised substantially to its elastic working temperature, while causing said microneedle array mold to be held in an appropriate position until a microneedle array three-dimensional pattern is formed in said plastic material;

by use of said temperature-controlled mold chamber, cooling said patterned plastic material below its deformable temperature; and

de-molding, by removing said microneedle array mold from contact with said patterned plastic material, thereby leaving behind a plastic microneedle array.

9. The method as recited in claim 8, wherein said plastic material comprises a biocompatible polymer.

10. The method as recited in claim 8, further comprising:

providing a vacuum during the molding process.

11. The method as recited in claim 8, wherein during said step of providing a heated plastic material into said temperature-controlled mold chamber, said microneedle array mold is pressed against a layer of said heated-plastic material that was previously placed in position upon a planar surface, thereby microembossing said plastic material.

12. The method as recited in claim 8, wherein during said step of providing a heated plastic material into said temperature-controlled mold chamber, said microneedle array mold is already in its molding position and molten plastic material is injected into said mold chamber, thereby micromolding said plastic material.

13. The method as recited in claim 8, further comprising:

forming a fluid-holding chamber in said patterned microneedle array by way of micromachining.

14. The method as recited in claim 8, further comprising:

forming a fluid-holding chamber in said patterned microneedle array by way of oxygen plasma etching.

15. The method as recited in claim 8, further comprising:

forming at least one through-hole in a base member of said patterned microneedle array, in which said microneedle array comprises hollow microneedles, by burning a hole through said base member that is substantially concentric with at least one of said hollow microneedles.

16. The method as recited in claim 8, further comprising:

during the step of de-molding, controlling the cool-down temperature to generate shear forces along a surface of hollow microneedle shapes within said patterned microneedle array, such that upon removal of said microneedle array mold, at least one sharp point is formed at the tip of said hollow microneedles.

17. A method of manufacturing a microneedle array, comprising:

providing a laminate material comprising two layers of biocompatible plastic;

providing a first mold having a plurality of projections that face against a surface of said laminate material;

placing said laminate material upon a first temperature-controlled surface and, by use of said first temperature-controlled surface, heating said laminate material to substantially its elastic working temperature;

pressing said first mold against one surface of said laminate material such that said plurality of projections extend completely through a first of the two layers of biocompatible plastic, thereby forming a plurality of through-holes in said first layer;

by use of said first temperature-controlled surface, cooling said laminate material below its deformable temperature;

detaching said two layers of biocompatible plastic, and retaining said first layer;

placing said first layer of biocompatible plastic upon a second temperature-controlled surface and, by use of said second temperature-controlled surface, heating said first layer of biocompatible plastic to substantially its elastic working temperature;

providing a second mold having a microneedle array pattern, and pressing said second mold against one surface of said first layer of biocompatible plastic, thereby forming a three-dimensional pattern comprising a microneedle array in said first layer of biocompatible plastic;

by use of said second temperature-controlled surface, cooling said patterned biocompatible plastic below its deformable temperature; and

de-molding, by removing said second mold from contact with said patterned biocompatible plastic, thereby leaving behind a plastic microneedle array that exhibits through-holes in its base element.

18. The method as recited in claim 17, wherein said biocompatible plastic laminate material comprises a biocompatible polymer.

19. The method as recited in claim 17, wherein said photoresist material comprises polymethylmethacrylate (PMMA).

20. The method as recited in claim 17, wherein said first mold and said second mold comprise nickel.

21. The method as recited in claim 17, further comprising:

providing a vacuum during the molding processes.