Renewable neural implant device and method

• US 5,554,148 A
• Filed: 05/26/1995
• Issued: 09/10/1996
• Est. Priority Date: 11/17/1987
• Status: Expired due to Term

• Current Assignee: Neurotech S.A. (LivaNova Plc)
• Original Assignee: Brown University
• Inventors: Aebischer, Patrick, DiCesare, Paul C., Mulhauser, Paul J., Goddard, Moses
• Primary Examiner(s): Green, Randall L.
• Assistant Examiner(s): BOCKELMAN, MARK
• Application Number:
  US08/453,571
• Time in Patent Office: 473 Days
• Field of Search: 604/27, 604/29, 604/93, 604/264, 604/890.1, 604/891.1, 604/264, 604/265, 604/174, 604/175, 604/93, 604/43, 604/282, 128/632, 128/658-659, 424/424-422
• US Class Current: 604/890.1
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• 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 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61M 2210/0687 Skull, cranium
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• CPC Class Codes: C12N 5/0614 Adrenal gland
• CPC Class Codes: C12N 5/0619 Neurons
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

Refillable immunoisolatory neurological therapy devices for local and controlled delivery of a biologically active factor to the brain of a patient. The devices include a cell chamber adapted for infusion with nsecretory cells and having at least one semipermeable or permselective surface across which biologically active factors secreted by the cells can be delivered to the brain. The devices also include means for introducing secretory cells into the cell chamber, and means for renewing the cells or cell medium.

Claims

1. A refillable immunoisolatory therapeutic device for implantation through a human skull and into a human brain, comprising:

an outer flexible cell chamber adapted for containing viable cells which secrete at least one biologically active factor, the outer cell chamber having a first end connected to a cap, a second end for positioning within the brain, and at least one semipermeable surface across which the active factor secreted by the viable cells can be delivered at ambient pressure to the brain, the cell chamber being adapted for infusion with the viable cells and for protecting the cells from immunogens,

an inner flushing duct with a proximal end and a distal end, the distal end open to the second end of the cell chamber,

the cap adapted to engage an anchoring means, for anchoring the cell chamber and the inner flushing duct to the human skull, the cap having accessing means for accessing the cell chamber and the inner flushing duct to introduce, flush and renew the viable cells,

the accessing means comprising an inner flushing duct port and an outer cell chamber port, the flushing duct port in fluid communication with the proximal end of the inner flushing duct, and the outer cell chamber port in fluid communication with the first end of the outer cell chamber,

a mandrel to protect the cell chamber.

2. The device of claim 1 wherein the semipermeable surface is permeable to a biologically active factor selected from the group consisting of gamma aminobutyric acid, serotonin, acetylcholine, norepinephrine, endorphins, enkephalins, dopamine, and precursors, agonists, active analogs, and active fragments thereof.

3. The device of claim 2 wherein the biologically active factor is a dopamine precursor comprising L-dopa.

4. The device of claim 2 wherein the biologically active factor is a dopamine agonist comprising bromocriptine.

5. The device of claim 2 wherein the biologically active factor is dopamine.

6. The device of claim 1 wherein the cell chamber further comprises a hydrophobic matrix.

7. The device of claim 6 wherein the hydrophobic matrix comprises an ethylene-vinyl acetate copolymer.

8. The device of claim 1 wherein the cell chamber comprises a hydrophilic matrix.

9. The device of claim 8 wherein the hydrophilic matrix comprises a hydrogel.

10. The device of claim 1 wherein the cell chamber further comprises an impermeable outer coating covering a portion of the cell chamber.

11. The device of claim 10 wherein the impermeable outer coating comprises polyurethane.

12. The device of claim 10 wherein the impermeable outer coating comprises ethylene-vinyl acetate.

13. The device of claim 1 wherein the cell chamber further comprises an outer membrane including angiogenic factors.

14. A refillable immunoisolatory therapeutic device for implantation through a human skull and into a human brain, comprising:

a flexible cell chamber adapted for containing viable cells which secrete at least one biologically active factor, the cell chamber comprising a first end, a second end for positioning within the brain, a cell chamber exterior wall surface, and at least one semipermeable surface in the second end, across which the active factor secreted by the viable cells can be delivered to the brain, the cell chamber being adapted for infusion with the viable cells and for protecting the viable cells from immunogens;

the cell chamber constructed as a U-tube with the open free ends of the U-tube connected at the first end of the cell chamber to a cap, the cap adapted to engage a skull anchoring means, for anchoring the cell chamber to a human skull,

the cap having accessing means comprising at least one port in fluid communication with at least one free end of the U-tube to introduce, flush and renew the viable cells,

a substantially rigid mandrel adapted to engage at least a portion of the cell chamber exterior wall surface during implantation in the brain, wherein the mandrel engages at least a portion of the cell chamber exterior wall surface during implantation and the mandrel being removable through a insertion port in the cap after implantation.

15. The device of claim 14 wherein:

the mandrel includes a portion that expands to engage at least a portion of the exterior wall surface of the cell chamber during implantation of the device and selectively collapses to fit through the insertion port for removal.

16. The device of claim 14 further comprising an outer, substantially rigid shield, the shield comprising two legs, the legs being closeable around the cell chamber when the shield is fully inserted and the legs being outwardly flexible to form a gap around the cell chamber during insertion and removal of the shield, so that the shield slidably fits through the insertion port and over the mandrel.

17. The device of claim 16 wherein the shield has tab means for engaging the mandrel and the mandrel includes an aperture adapted to at least partially receive the tab means to enable interlocked removal of the mandrel and shield from the cell chamber.

18. The device of claim 14 wherein the semipermeable surface is permeable to a biologically active factor selected from the group consisting of gamma aminobutyric acid, serotonin, acetylcholine, norepinephrine, endorphins, enkephalins, dopamine, and precursors, agonists, active analogs, and active fragments thereof.

19. The device of claim 18 wherein the biologically active factor is a dopamine precursor comprising L-dopa.

20. The device of claim 18 wherein the biologically active factor is a dopamine agonist comprising bromocriptine.

21. The device of claim 18 wherein the biologically active factor is dopamine.

22. The device of claim 14 wherein the cell chamber further comprises a hydrophobic matrix.

23. The matrix of claim 22 wherein the cell chamber further comprises an ethylene-vinyl acetate copolymer.

24. The device of claim 14 wherein the cell chamber comprises a hydrophilic matrix.

25. The device of claim 24 wherein the hydrophilic matrix comprises a hydrogel.

26. The device of claim 14 wherein the cell chamber further comprises an impermeable outer coating covering a portion of the cell chamber.

27. The device of claim 26 wherein the impermeable outer coating comprises polyurethane.

28. The device of claim 26 wherein the impermeable outer coating comprises ethylene-vinyl acetate.

29. The device of claim 14 wherein the cell chamber further comprises an outer membrane including angiogenic factors.