Method for manufacturing microstructures having multiple microelements with through-holes

• US 7,578,954 B2
• Filed: 02/24/2003
• Issued: 08/25/2009
• Est. Priority Date: 02/24/2003
• 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:
  US10/373,251
• Publication Number:
  US 20040164454A1
• Time in Patent Office: 2,374 Days
• Field of Search: None
• US Class Current: 264/154
• 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 1/24 Perforating by needles or pins
• CPC Class Codes: B26F 1/26 Perforating by non-mechanical means, e.g. by fluid jet
• 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 2201/034 Moulding
• CPC Class Codes: B81C 2201/036 Hot embossing

Abstract

A method is provided for manufacturing microstructures of the type which contain a substrate and an array of protruding microelements with through-holes, which are used in penetrating layers of skin. The microelements are embossed or pressed into an initial substrate structure, which in some embodiments is formed from extruded polymeric material, and in some cases from two layers of polymer that are co-extruded. The through-holes are formed from filled through-cylinders of a second material that is removed after the embossing or pressing step; in other instances, the through-holes are left hollow during the embossing or pressing step.

Claims

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

(a) providing a substrate of a first material, said substrate having a first substantially planar surface and a second substantially planar surface opposite said first surface, said substrate having a plurality of openings in the form of through-holes formed between said first and second surfaces; and

then

(b) pressing against the first surface of said substrate of material with an object having a predetermined shape to thereby form a plurality of permanent microelement protrusions in said first surface, said plurality of microelement protrusions being of at least one predetermined shape and size, each of said plurality of microelement protrusions having a base-shape that forms a perimeter along said first surface;

wherein at least one of said plurality of microelement protrusions exhibit at least one of said plurality of openings within their said perimeter, and said microelement protrusions are suitable for penetrating the stratum corneum of human skin.

2. The method as recited in claim 1, wherein a location of said plurality of openings in said substrate is one of:

(a) well-aligned with respect to the perimeters of said plurality of microelement protrusions, such that at least one of said plurality of openings fall within at least one of said perimeters; and

(b) semi-random, such that a number and density of spacing of said plurality of openings is sufficient so that at least one of said plurality of microelement protrusions exhibits at least one of said openings, even though many of said openings will not fall within at least one of said perimeters.

3. The method as recited in claim 1, wherein at least one of said plurality of openings are not completely closed by said pressing operation.

4. The method as recited in claim 1, wherein said step (b) of pressing against said substrate comprises one of:

embossing;

molding;

punching;

squeezing; and

stamping.

8. The method as recited in claim 1, wherein the substrate comprises polymethymethacrylate or polysulfone.

5. A method for constructing a microstructure, said method comprising the steps of:

(a) providing a substrate of a first material, said substrate having a first substantially planar surface and a second substantially planar surface opposite said first surface, said substrate having a plurality of openings in the form of through-holes formed between said first and second surfaces;

then

(b) pressing against the first surface of said substrate of material with an object having a predetermined shape to thereby form a plurality of microelement protrusions in said first surface, said plurality of microelement protrusions being of at least one predetermined shape and size, each of said plurality of microelement protrusions having a base-shape that forms a perimeter along said first surface;

wherein at least one of said plurality of microelement protrusions exhibit at least one of said plurality of openings within their said perimeter, and said microelement protrusions are suitable for penetrating the stratum corneum of human skin

(c) before said pressing step (b), placing a second material into at least one of said plurality of openings, said second material having at least one property that is different from at least one property of said first material; and

(d) after said pressing step (b), removing said second material from at least one of said plurality of openings.

6. The method as recited in claim 5, wherein said step (c) of placing a second material into at least one of said plurality of openings comprises one of:

(i) passing said substrate of a first material through a bath of said second material at a raised temperature, such that said second material readily flows into said plurality of openings; and

(ii) co-extruding said second material onto said substrate of a first material.

7. The method as recited in claim 5, wherein said step (d) of removing the second material comprises one of:

raising a temperature to above a melting point of said second material;

applying a chemical that dissolves said second material but not said first material;

applying a chemical that reacts with said second material but not said first material;

mechanically punching said second material from said plurality of openings; and

mechanically drilling said second material from said plurality of openings.

9. The method as recited in claim 5, wherein a location of said plurality of openings in said substrate is one of:

(a) well-aligned with respect to the perimeters of said plurality of microelement protrusions, such that at least one of said plurality of openings fall within at least one of said perimeters; and

(b) semi-random, such that a number and density of spacing of said plurality of openings is sufficient so that at least one of said plurality of microelement protrusions exhibits at least one of said openings, even though many of said openings will not fall within at least one of said perimeters.

10. The method as recited in claim 5, wherein said step of pressing against said substrate comprises one of:

embossing;

molding;

punching;

squeezing; and

stamping.