Microchip drug delivery devices

• US 7,070,590 B1
• Filed: 09/19/2000
• Issued: 07/04/2006
• Est. Priority Date: 07/02/1996
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Cima, Michael J., Santini, John T. Jr., Langer, Robert S.
• Primary Examiner(s): RODRIGUEZ, CRIS LOIREN
• Application Number:
  US09/665,303
• Time in Patent Office: 2,114 Days
• Field of Search: 604/890.1, 604/891.1, 604/892.1, 604/19
• US Class Current: 604/890.1
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• 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 5/14276 specially adapted for implantation
• CPC Class Codes: C25F 5/00 Electrolytic stripping of metallic layers or coatings
• CPC Class Codes: C25F 7/00 Constructional parts, or assemblies thereof, of cells for electrolytic removal of material from objects for both electrolytic coating and removal C25D; Servicing or operating
• CPC Class Codes: Y10T 137/8242 Electrical

Abstract

Devices are provided for the controlled release of drug or other molecules. The devices include (1) a substrate, which optionally includes two or more substrate portions bonded together, (2) at least two reservoirs in the substrate, (3) a release system disposed in the reservoirs that includes the molecules for release and optionally a matrix material, and (4) active or passive means for controlling release of the molecules from the reservoirs. In one embodiment, a reservoir cap is positioned on, or within a portion of, the reservoir and over the molecules, so that the molecules are controllably released from the device by diffusion through or upon disintegration of the reservoir cap.

Claims

1. An implantable medical device for the controlled release of drug molecules comprising:

a substrate;

at least two discrete reservoirs provided in spaced positions in the substrate; and

a release system disposed in the at least two reservoirs, the release system including drug molecules dispersed in a matrix material,

wherein the medical device is implantable inside a patient and the rate of release of the drug molecules from the reservoir in vivo is controlled by the matrix material.

2. The device of claim 1, wherein the substrate is comprised of two or more substrate portions bonded together.

3. The device of claim 1, wherein the matrix material comprises one or more hydrogels or synthetic polymers.

4. The device of claim 1, wherein the matrix material is non-degradable.

5. The device of claim 4, wherein release of the drug molecules from the reservoir is controlled by in vivo diffusion of the drug molecules from the matrix material.

6. The device of claim 4, wherein the non-degradable matrix material comprises one or more synthetic polymers selected from the group consisting of poly(ethers), poly(acrylates), poly(methacrylates), poly(vinyl pyrolidones), poly(vinyl acetates), poly(urethanes), celluloses, cellulose acetates, and poly(siloxanes).

7. The device of claim 1, wherein the drug molecules are heterogeneously dispersed within the reservoirs.

8. The device of claim 1, wherein the drug molecules comprise one or more therapeutic agents selected from the group consisting of anesthetics, chemotherapeutic agents, hormones, immunomodulators, ion channel regulators, and antibiotics.

9. The device of claim 1, wherein the dose of drug molecules in one of the reservoirs is different from the dose of drug molecules in another of the reservoirs.

10. The device of claim 1, wherein the kinetics of release of the drug molecules from one of the reservoirs is different from the kinetics of release of the drug molecules from another of the reservoirs.

11. The device of claim 1, wherein at least one of the reservoirs comprises two or more layers of the release system.

12. The device of claim 11, wherein a first drug is contained in a first layer of the two or more layers, and a second drug is contained in a second layer of the two or more layers.

13. The device of claim 1, further comprising at least two discrete non-degradable reservoir caps covering the at least two reservoirs, which caps further control the kinetics of release of the drug molecules from the reservoirs.

14. The device of claim 13, wherein the reservoir caps comprises one or more synthetic polymers.

15. The device of claim 1, comprising at least two rows of the at least two reservoirs in an array in the device.

16. The device of claim 15, wherein a first release system is the reservoirs of a first row and a second release system is in the reservoirs of another of the at least two rows, the first release system releasing the one or more drugs at a rate or in a dosage amount different from release of the one or more drugs from the second release system.

17. The device of claim 1, wherein the substrate comprises a metal.

18. The device of claim 1, wherein the reservoirs are made by a microfabrication process.

19. An implantable medical device for the controlled release of drug molecules comprising:

a substrate;

at least two discrete reservoirs provided in spaced positions in the substrate;

a release system disposed in the at least two reservoirs, the release system including drug molecules dispersed in a matrix material;

at least two discrete degradable reservoir caps covering the at least two reservoirs,

wherein the rate of release of the drug molecules from the reservoir in vivo is controlled by the matrix material.

20. The device of claim 19, wherein one of the reservoir caps is formed of a first material and the other of the at least two reservoir caps is formed of a second material, wherein the first material has a different disintegration rate in vivo compared to the second material.

21. The device of claim 19, wherein one of the reservoir caps has a first thickness and the other of the at least two reservoir caps has a second, greater thickness.

22. The device of claim 19, wherein the reservoir caps comprises one or more synthetic polymers.

23. An implantable medical device for the controlled release of drug molecules comprising:

a substrate;

at least two discrete reservoirs provided in spaced positions in the substrate;

a release system disposed in the at least two reservoirs, the release system including drug molecules dispersed in a degradable matrix material;

wherein the rate of release of the drug molecules from the reservoir in vivo is controlled by the matrix material.

24. The device of claim 23, wherein the release of the drug molecules from the reservoirs is controlled by the in vivo disintegration of the matrix material.

25. The device of claim 23, wherein the disintegration of the degradable matrix material is by dissolution, enzymatic hydrolysis, or erosion.

26. The device of claim 23, wherein the degradable matrix material comprises one or more synthetic polymers selected from the group consisting of poly(amides), poly(esters), poly(anhydrides), poly(orthoesters), poly(carbonates), copolymers thereof, and mixtures thereof.

27. The device of claim 23, wherein the degradable matrix material comprises one or more synthetic polymers selected from the group consisting of poly(lactic acids), poly(glycolic acids), poly(lactic-co-glycolic acids), poly(caprolactones), and mixtures thereof.

28. The device of claim 23, wherein the at least two reservoirs individually comprise at least two layers of a release system and at least one layer of a degradable or soluble material which does not comprise the one or more drugs.

29. The device of claim 23, wherein the release system further comprises one or more pharmaceutically acceptable carriers, excipients, or diluents.

30. A microchip device for the controlled release of molecules comprising:

a substrate;

an array of two or more spaced apart reservoirs in the substrate,

a release system disposed in the reservoirs, the release system comprising chemical molecules for release; and

discrete polymeric reservoir caps positioned over or within openings of said at least two reservoirs,

wherein the release of the molecules from each reservoir is passively controlled by disintegration of the reservoir cap.

31. The device of claim 30, wherein the chemical molecules comprise one or more drugs for in vivo release.

32. The device of claim 30, wherein the substrate is comprised of two or more substrate portions bonded together.