Method for manufacturing microstructures having multiple microelements with through-holes

• US 20040164454A1
• Filed: 02/24/2003
• Published: 08/26/2004
• Est. Priority Date: 02/24/2003
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: The Procter & Gamble Company
• Inventors: Gartstein, Vladimir, Sherman, Faiz Feisal
• Granted Patent: US 7,578,954 B2
• Time in Patent Office: Days
• US Class Current: 264/293
• 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 formed between said first and second surfaces; and

(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.

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.

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

(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.

8. The method as recited in claim 6, wherein said step (c)(ii) of co-extruding the second material forms an additional layer upon the second surface of said substrate of a first material, and said step (d) of removing said second material from substantially all of said plurality of openings also removes said additional layer of the second material from the second surface of said substrate of a first material.

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.

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

(a) providing a substrate of a substantially solid material, said substrate having a first surface exhibiting a plurality of microelement protrusions being of at least one predetermined shape and size, each having a base-shape that forms a perimeter along said first surface, said substrate having a second substantially planar surface opposite said first surface, said substrate being substantially non-porous between said first and second surfaces;

(b) providing a mask plate having a third substantially planar surface and a fourth surface opposite said third surface, said mask plate exhibiting a plurality of openings formed between said third and fourth surfaces;

(c) placing the third substantially planar surface of said mask plate proximal to the second substantially planar surface of said substrate, and forcing a fluid under pressure from the fourth surface of said mask plate through said plurality of openings, thereby forming a plurality of fluidic jets under pressure; and

(d) forming a second plurality of openings in said substrate by way of said plurality of pressurized fluidic jets, wherein at least one of said plurality of microelement protrusions contain at least one of said second plurality of openings within their said perimeter.

12. The method as recited in claim 11, wherein said pressurized fluidic jets comprise one of:

steam;

heated gas;

liquid solvent; and

heated liquid.

13. The method as recited in claim 11, further comprising the steps of:

(a) holding said substrate against said mask plate by way of a holding fluidic pressure, wherein said holding fluidic pressure comprises one of (i) gas pressure and (ii) liquid pressure; and

(b) wherein said holding fluidic pressure is less than a pressure of said pressurized fluidic jets.

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

(a) providing a substrate of a predetermined solid material, said substrate having a first substantially planar surface and having a second substantially planar surface opposite said first surface, said substrate being substantially non-porous between said first and second surfaces;

(b) providing a first object having a first predetermined shape and a second object having a second predetermined shape, and positioning said substrate between said first object and said second object by placing the second substantially planar surface of said substrate proximal to said second object, while placing said first object proximal to the first substantially planar surface of said substrate; and

(c) simultaneously pressing said first object against the first surface and pressing the second object against the second surface of said substrate of solid material;

(i) wherein said first surface is pressed by said first object, such that said first predetermined shape forms a plurality of microelement protrusions in said first surface, said plurality of microelement protrusions being of at least one predetermined shape and size, each having a base-shape that forms a perimeter along said first surface;

(ii) wherein said second surface is pressed by said second object, such that said second predetermined shape forms a plurality of microholes within said substrate, at least one of said plurality of microholes extending completely through said substrate between said first and second surfaces;

(iii) wherein at least one of said plurality of microelement protrusions contain at least one of said plurality of microholes within their said perimeter; and

(iv) wherein the first predetermined shape of said first object and the second predetermined shape of the second object produce a self-aligning effect when said first and second objects are pressed toward one another in said pressing step (c).

15. The method as recited in claim 14, wherein the first predetermined shape of said first object creates a shape of said plurality of microelement protrusions that are substantially pyramidal.

16. The method as recited in claim 15, wherein the second predetermined shape of said second object creates a shape of said plurality of microholes, in which a position of said plurality of microholes is located at one of:

(a) a substantially center peak position of said substantially pyramidal microelement protrusions; and

(b) within a sloped face of said substantially pyramidal microelement protrusions.

17. The method as recited in claim 14, wherein the first predetermined shape of said first object, and the second predetermined shape of said second object, are such that a projecting surface of said second object will be within a perimeter of a sloped surface of a depression in said first object when said first and second objects are brought toward one another, and said projecting surface of said second object will thus tend to seek a self-aligning center position within said depression in said first object.

18. The method as recited in claim 17, wherein the second predetermined shape of said second object can vary while maintaining its self-aligning characteristics when used with a first object, even when said first predetermined shape of said first object has remained constant.

19. The method as recited in claim 14, 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.

20. The method as recited in claim 14, wherein said step of pressing against said substrate comprises one of:

embossing;

molding;

punching;

squeezing; and

stamping.