Microfabricated devices for the delivery of molecules into a carrier fluid

• US 6,491,666 B1
• Filed: 11/17/2000
• Issued: 12/10/2002
• Est. Priority Date: 11/17/1999
• Status: Expired due to Term

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: MicroCHIPS Inc.
• Inventors: Cima, Michael J., Santini, John T. Jr., Ausiello, Dennis, Langer, Robert S., Uhland, Scott A., Hutchinson, Charles E.
• Primary Examiner(s): Doerrler, William C.
• Assistant Examiner(s): Zec, Filip
• Application Number:
  US09/715,493
• Time in Patent Office: 753 Days
• Field of Search: 604/191, 604/93.01, 604/19, 604/890.1, 128/899, 216/2, 216/39, 216/56
• US Class Current: 604/191
• CPC Class Codes: A23L 2/52 Adding ingredients adding preservatives A23L2/44
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2250/0035 differing in release or diffusion time
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• 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 9/0097 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: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 15/0031 by bursting or breaking the package, i.e. without cutting or piercing
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/005 the dosages being arranged on a cylindrical surface
• CPC Class Codes: A61M 15/008 Electronic counters
• CPC Class Codes: A61M 15/0083 Timers
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 2205/8225 using incorporated gas cartridges for the driving gas
• CPC Class Codes: A61M 5/1407 Infusion of two or more substances

Abstract

Apparati and methods are provided for the delivery of molecules to a site via a carrier fluid. The apparati include microchip devices which have reservoirs containing the molecules for release. The apparati and methods provide for active or passive controlled release of the molecules. Preferred embodiments include systems for intravenous administration of drugs, wherein drug molecules are released from the microchip devices into a carrier fluid ex vivo, such as a saline solution, forming a drug/saline solution mixture which is then delivered to a patient intravenously.

Claims

1. An apparatus for the controlled release of molecules comprising

(i) a microchip device having a plurality of reservoirs containing the molecules for release, and

(ii) a container of a carrier fluid,

wherein the molecules are combined with the carrier fluid following release of the molecules from the reservoir.

2. The apparatus of claim 1 further comprising a mixing chamber in fluid communication with the container, wherein the molecules are combined with the carrier fluid in the mixing chamber.

3. The apparatus of claim 1 further comprising a mixer.

4. The apparatus of claim 1 further comprising a pump.

5. The apparatus of claim 1 wherein the molecules are drug molecules and the carrier fluid is a physiologically acceptable fluid for intravenous administration.

6. The apparatus of claim 5 wherein the reservoirs of the microchip device are covered by reservoir caps which can be selectively ruptured or disintegrated to release the molecules into the carrier fluid ex vivo.

7. The apparatus of claim 5 wherein the carrier fluid is selected from the group consisting of water, saline, blood plasma, whole blood, and sugar solutions.

8. The apparatus of claim 5 wherein the container is an IV bag or bottle.

9. The apparatus of claim 5 further comprising a mixing chamber.

10. The apparatus of claim 9 further comprising a flexible, hollow tube extending from the mixing chamber.

11. The apparatus of claim 1 wherein the molecules in the reservoirs are in a stable dry form prior to contact with the carrier fluid.

29. A method for the delivery of molecules to a site comprising

(a) providing the apparatus of claim 1;

(b) selectively exposing the reservoirs of the microchip device to the carrier fluid, thereby causing the molecules to be released from the reservoirs and combine with the carrier fluid to form a molecule/carrier fluid mixture, and

(c) transporting the molecule/carrier fluid mixture to the site.

30. The method of claim 29 wherein the site is in a human or animal and wherein the molecules are drug molecules.

31. The method of claim 30 wherein the transporting step is by intravenous administration.

32. The method of claim 31 wherein the carrier fluid is selected from the group consisting of water, saline, blood plasma, whole blood, and sugar solutions.

12. An apparatus for delivery of a drug into a carrier fluid for subsequent administration to a patient comprising

(i) a microchip device having a plurality of reservoirs containing the molecules for release, and

(ii) a mixing chamber,

wherein the molecules are combined with the carrier fluid in the mixing chamber following release of the molecules from the reservoir.

13. The apparatus of claim 12 further comprising an IV bag or bottle.

14. The apparatus of claim 12 wherein the mixing chamber is an IV bag or bottle.

15. The apparatus of claim 12 wherein the carrier fluid is selected from the group consisting of water, saline, blood plasma, whole blood, and sugar solutions.

16. The apparatus of claim 12 wherein the mixing chamber comprises an outlet from which a mixture of carrier fluid and drug flows, and wherein a length of hollow tubing is connected to the outlet for intravenous connection to the patient.

17. The apparatus of claim 12 comprising two or more microchip devices.

18. The apparatus of claim 12 wherein the mixing chamber is provided in a console adapted to receive one or more replaceable cartridges, each of which contains at least one microchip device.

19. The apparatus of claim 12 further comprising an electronic control system in communication with the microchip device.

20. The apparatus of claim 19 wherein the communication is wireless.

21. The apparatus of claim 12 having a label identifying the drug contained in the microchip device.

22. The apparatus of claim 21 wherein the label comprises information in an electronically readable form.

23. The apparatus of claim 12 wherein the mixing chamber is integrated into a metered dose inhaler.

33. A method for the delivery of molecules to a site comprising

(a) providing the apparatus of claim 12;

(b) selectively exposing the reservoirs of the microchip device to a carrier fluid, thereby causing the molecules to be released from the reservoirs and combine with the carrier fluid to form a drug/carrier fluid mixture, and

(c) transporting the drug carrier fluid mixture to the site.

34. The method of claim 33 wherein the site is in a human or animal and wherein the molecules are drug molecules.

35. The method of claim 34 wherein the transporting step is by intravenous administration.

36. The method of claim 35 wherein the carrier fluid is selected from the group consisting of water, saline, blood plasma, whole blood, and sugar solutions.

24. A device for the release of molecules in vivo comprising

a medical stent, and

a microchip device having a plurality of reservoirs containing the molecules for release,

wherein the microchip device is integrated into or is attached to a surface of the medical stent.

25. A device for the release of drug molecules in vivo comprising

a medical stent having a plurality of microfabricated reservoirs containing the molecules for release.

26. The device of claim 25 wherein the stent is a cardiovascular stent.

27. The device of claim 25 wherein the drug is an anti-restenosis agent.

28. A device for the controlled delivery of molecules comprising

(i) a microchip device having a plurality of reservoirs containing the molecules and sealed by reservoir caps, and

(ii) an implanted delivery system comprising a pump,

wherein the reservoirs of the microchip device are selectively exposed to the flow of fluid, in vivo, in the delivery system, and wherein the molecules are released from the reservoirs, upon disintegration of the reservoir caps, during fluid flow in the delivery system.