Method for manufacturing microstructures having hollow microelements using fluidic jets during a molding operation

• US 7,572,405 B2
• Filed: 05/25/2004
• Issued: 08/11/2009
• Est. Priority Date: 06/02/2003
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Gartstein, Vladimir, Sherman, Faiz Feisal
• Primary Examiner(s): HUSON, MONICA ANNE
• Application Number:
  US10/853,658
• Publication Number:
  US 20060076718A1
• Time in Patent Office: 1,904 Days
• Field of Search: None
• US Class Current: 264/504
• 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: B26F 1/26 Perforating by non-mechanical means, e.g. by fluid jet
• CPC Class Codes: B29C 2043/023 having a plurality of grooves
• CPC Class Codes: B29C 2043/3233 exerting pressure on mould parts
• CPC Class Codes: B29C 2059/023 Microembossing
• CPC Class Codes: B29C 2793/0045 Perforating
• CPC Class Codes: B29C 33/0033 constructed for making articles provided with holes
• CPC Class Codes: B29C 33/3814 Porous moulds adapted for vacuum forming B29C51/365
• CPC Class Codes: B29C 33/3857 by making impressions of one or more parts of models, e.g. shaped articles and including possible subsequent assembly of the parts
• 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 59/022 characterised by the disposition or the configuration, e.g. dimensions, of the embossments or the shaping tools therefor

Abstract

A method is provided for constructing microstructures that can penetrate skin layers, in which the microelements are formed during a molding process while fluidic jets produce openings in the microelements. The structures used in the molding process are formed by tooling that creates the shapes of the microelements in a material deposition step, and also creates the sizes and shapes of the openings that will be formed by the fluidic jets.

Claims

1. A method for constructing a microstructure comprising an array of microneedles designed to penetrate the stratum corneum of human skin, said method comprising:

(a) providing a moldable material to be formed into a predetermined shape;

(b) during a molding procedure, forcing a predetermined fluid under pressure toward a surface of said moldable material, said predetermined fluid forming at least one opening at said surface; and

(c) substantially solidifying said moldable material while said pressurized predetermined fluid continues to flow toward said surface, thereby forming a solid microstructure which includes said at least one opening at said surface, wherein the solid microstructure has the predetermined shape comprising an array of microneedles protruding from a substrate wherein said microneedles are able to penetrate the stratum corneum of human skin.

2. The method as recited in claim 1, wherein:

said at least one opening extends completely through said solid microstructure.

3. The method as recited in claim 1, wherein:

said at least one opening forms an indentation that does not extend completely through said solid microstructure.

4. The method as recited in claim 1, wherein said molding procedure comprises one of:

(a) injection molding, (b) embossing, and (c) die casting.

5. The method as recited in claim 1, further comprising:

providing a micromold having a first mold-half and a second mold-half, said first mold-half including a plurality of openings through which said predetermined fluid is forced under pressure.

6. The method as recited in claim 5, wherein:

said second mold-half comprises one of;

(a) a material that is substantially non-porous with respect to said moldable material, but is substantially porous with respect to said predetermined fluid; and

(b) a material that is substantially non-porous with respect to said moldable material, and is also substantially non-porous with respect to said predetermined fluid.

7. The method as recited in claim 5, wherein:

(a) said moldable material is formed into a three-dimensional negative form of said first and second mold-halves, and comprises (i) a substrate having a first surface and a second surface opposite said first surface, and (ii) at least one protrusion extending from the first surface of said substrate; and

(b) said at least one opening is physically located at one of;

(i) one of said at least one protrusion, and (ii) along a substantially planar portion of the first surface of said substrate.

8. The method as recited in claim 7, wherein:

said at least one protrusion exhibits a length in the range of 0.1-3000 microns.

9. A method for constructing a micromold, said method comprising:

(a) providing a tooling structure having a first surface and a second surface opposite said first surface, and having a substrate having a plurality of protrusions formed upon said first surface, said plurality of protrusions exhibiting at least one height;

(b) depositing a material upon the first surface of said tooling structure, said material having a thickness that is generally less than said at least one height of said plurality of protrusions; and

(c) separating said material from said tooling structure to form a micromold, said micromold exhibiting a first plurality of openings that correspond to a portion of a three-dimensional negative form of said plurality of protrusions of the tooling structure along said thickness of said material, wherein said depositing step comprises one of;

(a) electroplating;

(b) spin coating;

(c) vapor deposition;

(d) injection molding; and

(e) casting.

10. The method as recited in claim 9, further comprising:

(d) providing a backing member;

(e) introducing a moldable material between said micromold and said backing member;

(f) during a molding procedure, forcing a predetermined fluid under pressure through said first plurality of openings in said micromold toward a surface of said moldable material, said predetermined fluid forming a second plurality of openings at said surface of said moldable material; and

(g) substantially solidifying said moldable material while said pressurized predetermined fluid continues to flow toward said surface of said moldable material, thereby forming a solid microstructure which includes said second plurality of openings at said surface of said moldable material.

11. The method as recited in claim 10, wherein one of the following statements holds:

(a) said second plurality of openings extend completely through said solid micro structure;

(b) said second plurality of openings form at least one indentation that does not extend completely through said solid microstructure;

or (c) a first group of the second plurality of openings extends completely through said solid microstructure, while a second group of the second plurality of openings forms at least one indentation that does not extend completely through said solid microstructure.

12. The method as recited in claim 10, wherein said molding procedure comprises one of:

(a) injection molding, (b) embossing, and (c) die casting.

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

(h) providing a mask member which exhibits a third plurality of openings;

(i) placing said mask member substantially against a surface of said micromold that faces away from said backing member, wherein by such placement, said third plurality of openings is substantially well-aligned with said first plurality of openings of said micromold; and

(j) during said molding procedure, forcing said predetermined fluid under pressure through both said third plurality of openings of said mask member and said first plurality of openings of said micromold toward said third surface of said moldable material.

14. The method as recited in claim 13, wherein said mask member exhibits one of the following physical characteristics:

(a) said mask member comprises a substantially flat plate;

(b) said mask member exhibits a shape similar to said micromold, but inverted in orientation; and

(c) at said surface between said mask member and micromold, an inner area of the third plurality of openings of said mask member is generally smaller than an inner area of the first plurality of openings of said micromold.

15. The method as recited in claim 10, wherein:

said backing member comprises one of;

(a) a material that is substantially non-porous with respect to said moldable material, but is substantially porous with respect to said predetermined fluid; and

(b) a material that is substantially non-porous with respect to said moldable material, and is also substantially non-porous with respect to said predetermined fluid.

16. The method as recited in claim 10, wherein:

(a) said moldable material is formed into a three-dimensional negative form of said backing member and said micromold, and comprises;

(i) a substrate having said third surface and a fourth surface opposite said third surface, and (ii) a second plurality of protrusions extending from the third surface of said substrate; and

(b) at least some of said second plurality of openings are physically located at one of;

(i) one of said second plurality of protrusions, and (ii) along a substantially planar portion of the third surface of said substrate.

17. The method as recited in claim 16, wherein:

said second plurality of protrusions exhibits a length in the range of 0.1-3000 microns.

18. A method for constructing a microstructure, said method comprising:

(a) providing a tooling structure having a first surface and a second surface opposite said first surface, and having a first substrate having a plurality of protrusions formed upon said first surface, said plurality of protrusions exhibiting at least one height;

(b) depositing a first material upon the first surface of said tooling structure, said first material having a thickness that is generally less than said at least one height of said plurality of protrusions;

(c) releasing said first material from said tooling structure, said first material exhibiting a plurality of openings that correspond to a portion of a three-dimensional negative form of said plurality of protrusions of the tooling structure along said thickness of said first material, said plurality of openings exhibiting at least one predetermined inner area proximal to a first surface of said first material;

(d) providing a backing member at a predetermined and spaced-apart distance from a second surface of said first material, said fourth surface being opposite said first surface of the first material, said backing member exhibiting comparatively little porosity with respect to a moldable second material, but exhibiting substantial porosity with respect to a predetermined fluid;

(e) introducing said moldable second material between said backing member and the second surface of said first material, and forcing said predetermined fluid under pressure through said plurality of openings of the first material to form at least one channel in said second material between said first material and said backing member, and substantially solidifying said second material while said pressurized predetermined fluid continues to flow through said plurality of openings; and

(f) separating said solidified second material from said backing member and said first material, said solidified second material exhibiting a second substrate and exhibiting a plurality of microelements that substantially correspond in size and shape to a three-dimensional negative form of said plurality of openings in the first material, and further exhibiting said at least one channel running completely through said second substrate and at least one of said plurality of micro elements.

19. The method as recited in claim 18, wherein said plurality of openings are smaller in area proximal to said first surface of said first material than they are in inner area proximal to said second surface of said first material.