System for delivery of drugs by transport

• US 5,983,136 A
• Filed: 09/15/1997
• Issued: 11/09/1999
• Est. Priority Date: 09/17/1996
• Status: Expired due to Term

• Current Assignee: Deka Products Limited Partnership
• Original Assignee: Deka Products Limited Partnership
• Inventors: Kamen, Dean L.
• Primary Examiner(s): Coggins, Wynn Wood
• Assistant Examiner(s): KENNEDY, SHARON E
• Application Number:
  US08/929,984
• Time in Patent Office: 785 Days
• Field of Search: 604/20, 604/21, 604/891.1, 604/264, 604/272, 604/175, 604/239, 604/27, 604/28, 604/35, 604/19, 604/22, 604/51, 607/120, 607/126, 607/127, 607/128, 607/130, 607/131, 607/152, 428/901, 428/597, 428/315.9
• US Class Current: 604/21
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 2037/0038 having a channel at the side surface
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

A method and apparatus for introducing a fluid agent into body tissue by causing transport of the fluid agent into the dermis of the subject. The outer surface of the skin of the subject is drawn against a plurality of micropenetrators such that microfissures are cloven into the epidermis and fluid may be introduced for diffusion or suction within the dermis. Suction creates a pressure gradient within the dermis to cause fluid take-up by the dermal tissue. The micropenetrators are produced by punching an array of protrusions in the surface of a thin sheet creating sharp edges for penetrating the epidermis.

Claims

1. A method for transporting a substance across an outer boundary of a permeable medium having at least one microfissure, the method comprising:

a. creating a pressure gradient along at least one path, each path running parallel to the outer boundary of the permeable medium from a first zone of the permeable medium to a second zone of the permeable medium proximate to the first zone, the first and second zones each being proximate to the outer boundary of the permeable medium; and

b. causing transport of the substance across the outer boundary of the permeable medium through at least one microfissure.

2. A method according to claim 1, wherein the substance is drawn into permeable medium.

3. A method according to claim 1, wherein the substance is drawn out of the permeable medium.

4. A method according to claim 1, wherein the substance is a liquid.

5. A method according to claim 1, wherein the substance is a therapeutic agent.

6. A method according to claim 1, wherein the permeable medium is body tissue.

7. A method according to claim 1, wherein the step of creating a pressure gradient along at least one path running between zones of the permeable medium includes puncturing at least one microfissure in the outer boundary of the permeable medium with at least one micropenetrator.

8. A method according to claim 1, wherein the step of creating a pressure gradient along at least one path running between zones of the permeable medium includes applying suction to a portion of the outer boundary of the permeable medium.

9. A method according to claim 1, wherein the step of creating a pressure gradient between zones of the permeable medium includes puncturing a plurality of microfissures in the permeable medium with a plurality of micropenetrators and applying suction to a subset of the micropenetrators.

10. A method according to claim 1, wherein the step of creating a pressure gradient between zones of the permeable medium includes puncturing a plurality of microfissures in the permeable medium with a plurality of micropenetrators and applying suction to a subset of the microfissures.

11. A method according to claim 1, wherein the step of puncturing at least one microfissure into the outer surface of the permeable medium with at least one micropenetrator includes applying suction to a portion of the outer boundary of the permeable medium substantially surrounding the contact between at least one micropenetrator and the outer boundary of the permeable medium.

15. An apparatus according to claim 1 further comprising a partial vacuum for drawing the outer surface of the permeable medium against at least one micropenetrator.

20. A method according to claim 1, wherein the pressure at the second zone is below ambient pressure exterior to the outer boundary of the porous medium.

12. An apparatus for causing the transport of a substance across an outer boundary of a permeable medium, the apparatus comprising:

a. a micropenetrator for penetrating the outer surface of a first zone of the permeable medium to a depth no greater than 1000 micrometers, thereby creating a microfissure;

b. a vacuum arrangement that applies a partial vacuum to a second zone of the permeable medium, the second zone proximate to the first zone, thereby creating a pressure gradient along a path running from the microfissure to the second zone of the permeable medium, so that the pressure at the second zone is below ambient pressure external to the outer boundary of the permeable medium; and

c. a reservoir for supplying a substance to the micropenetrator so as to cause transport of the substance into the permeable medium.

13. An apparatus according to claim 12, further comprising:

a. at least one sensor having an output for monitoring the quantity of the substance transported across the outer boundary of the permeable medium; and

b. a controller for regulating the rate of supply of the substance by the reservoir based on the output of each sensor.

14. An apparatus according to claim 12, further comprising:

a. at least one sensor having an output for monitoring a biological response to transport of the substance across the outer boundary of the permeable medium; and

b. a controller for regulating the rate of supply of the substance supplied by the reservoir based on the output of each sensor.

16. An apparatus for transporting a substance across the outer boundary of a permeable medium, the apparatus comprising:

a. a platen having a first and a second orifice, the first orifice characterized by a first pressure and the second orifice characterized by a second pressure, the difference between the first pressure and the second pressure causing a pressure gradient parallel to the outer boundary of the permeable medium;

b. at least one micropenetrator coupled to the platen for cleaving at least one microfissure in the outer boundary of the permeable medium; and

c. an arrangement for guiding a substance into the permeable medium via the at least one microfissure based at least in part on the pressure gradient.

17. A method of manufacture for producing an apparatus for transporting a substance across the outer boundary of a permeable medium, the method comprising:

a. punching an array of protrusions having central orifices in the surface of a thin planar platen;

b. coupling a plenum to a first subset of the orifices in the platen; and

c. applying suction to a second subset of the orifices in the platen.

18. A method of manufacture according to claim 17, wherein the step of punching an array of protrusions includes punching conical protrusions.

19. A method of manufacture for producing an apparatus for transporting a substance across the outer boundary of a permeable medium, the method comprising:

a. punching an array of peninsular tongues in the surface of a thin planar platen;

b. depressing the peninsular tongues below the surface of the platen such as to create orifices in the platen;

c. coupling a first plenum to a first subset of the orifices in the platen;

d. coupling a second plenum to a second set of the orifices in the platen.

21. A method for transporting a substance across the outer boundary of a permeable medium, the method comprising:

a. providing at least one micropenetrator for cleaving at least one microfissure in the outer boundary of the permeable medium;

b. creating a pressure gradient parallel to the outer boundary of the permeable medium; and

c. guiding a substance into the permeable medium via the at least one microfissure on the basis at least of the pressure gradient.

22. A method of manufacture for producing an apparatus for transporting a substance across the outer boundary of a porous medium, the method comprising:

a. punching an array of protrusions having central orifices in the surface of a thin planar platen;

b. coupling a first plenum to a first subset of the orifices in the platen;

c. coupling a second plenum to a second set of the orifices in the platen.