Neurological therapy devices

• US 5,106,627 A
• Filed: 11/14/1990
• Issued: 04/21/1992
• 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, Winn, Shelley R.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US07/613,109
• Time in Patent Office: 524 Days
• Field of Search: 424/424, 424/422, 424/423, 435/177, 435/178, 435/180, 435/181, 530/399, 604/890.1, 604/892.1
• US Class Current: 424/424
• 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 thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• 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

Neurological therapy devices are disclosed for the local and controlled delivery of a neurotransmitter to the brain of a subject suffering from neurotransmitter deficiency or dysfunction. In one embodiment the device includes a biocompatible, implantable, and retrievable polymeric insert including a source of neurotransmitter embedded therein. In another embodiment, the device includes a retrievable source of neurotransmitter including at least one neurotransmitter-secreting cell encapsulated within a semipermeable membrane allowing the diffusion therethrough of the neurotransmitter, and further includes a source of growth factor in close proximity to the neurotransmitter-secreting cells.

Claims

1. A neurological therapy device for the local and controlled delivery of a neurotransmitter to the brain of a subject, said device comprising:

a source of neurotransmitter including at least one neurotransmitter-secreting cell encapsulated within a semipermeable membrane, said semipermeable membrane allowing the diffusion therethrough of said neurotransmitter; and

a source of a growth factor located in close proximity to said encapsulated, neurotransmitter-producing cell for the maintenance of said neurotransmitter-producing cell,

said source of said growth factor selected from the group consisting of an implantable, biocompatible, polymeric insert containing said growth factor, and at least one growth factor-producing cell encapsulated within a semipermeable membrane that allows the diffusion therethrough of said growth factor,

said source of neurotransmitter and said source of growth factor including access means for retrieval from the brain.

2. The device of claim 1 wherein said neurotransmitter is selected from the group consisting of gamma aminobutyric acid, serotonin, acetylcholine, norepinephrine, endorphins, enkephalins, dopamine, and precursors, agonists, active analogs, and active fragments of said neurotransmitter.

3. The device of claim 2 wherein said neurotransmitter is the dopamine precursor L-dopa.

4. The device of claim 2 wherein said neurotransmitter is the dopamine agonist bromocriptine.

5. The therapy device of claim 1 wherein said semipermeable membrane within which said neurotransmitter-secreting cell is encapsulated is impermeable to viruses, antibodies, complement, and proteases.

6. The device of claim 1 wherein said semipermeable membrane includes pores having a molecular weight exclusion of from about 50 kD to about 100 kD.

7. The device of claim 1 wherein said semipermeable membrane comprises an acrylic copolymer.

8. The device of claim 1 wherein said neurotransmitter-secreting cell comprises an allograft.

9. The device of claim 1 wherein said neurotransmitter-secreting cell comprises a xenograft.

10. The device of claim 1 wherein said neurotransmitter-secreting cell comprises a neuron.

11. The device of claim 1 wherein said neurotransmitter-secreting cell comprises an adrenal medulla chromaffin cell.

12. The device of claim 1 wherein said neurotransmitter-secreting cell is a neuroblastic PC12 cell.

13. The therapy device of claim 1 wherein said neurotransmitter-secreting cell has been genetically engineered to produce said neurotransmitter.

14. The device of claim 1 wherein said growth factor comprises nerve growth factor.

15. The device of claim 1 wherein said growth factor comprises fibroblast growth factor.

16. The therapy device of claim 1 wherein said source of growth factor comprises an implantable, biocompatible, polymeric insert containing said growth factor.

17. The device of claim 16 wherein said source of growth factor comprises a polymeric insert includes pores having a molecular weight exclusion of from about 1 kD to about 1,000 kD.

18. The device of claim 17 wherein said polymeric insert contains pores having a molecular weight exclusion of about 25 kD to about 100 kD.

19. The device of claim 16 wherein said polymeric insert comprises a hydrophobic matrix.

20. The device of claim 19 wherein said hydrophobic matrix comprises ethylene-vinyl acetate copolymer.

21. The device of claim 16 Wherein said polymeric insert comprises a hydrophilic matrix.

22. The device of claim 21 wherein said hydrophilic matrix comprises a hydrogel.

23. The device of claim 16 wherein said polymeric insert further comprises an outer coating impermeable to said growth factor, said coating covering a portion of said insert for the controlled release of said growth factor from the uncoated portion of said insert.

24. The device of claim 23 wherein said impermeable outer coating comprises polyurethane.

25. The device of claim 23 wherein said outer coating comprises ethylene-vinyl impermeable acetate.

26. The therapy device of claim 1 wherein said source of growth factor comprises at least one growth factor-secreting cell encapsulated within a semipermeable membrane, said membrane allowing the diffusion therethrough of said growth factor.

27. The therapy device of claim 26 wherein said semipermeable membrane within which said growth factor-secreting cell is encapsulated is impermeable to viruses, antibodies, complement, and proteases.

28. The device of claim 26 wherein said semipermeable membrane includes pores having a molecular weight exclusion of from about 50 kD to about 100 kD.

29. The device of claim 26 wherein said semipermeable membrane comprises an acrylic copolymer.

30. The device of claim 26 wherein said growth factor-secreting cell comprises an allograft.

31. The device of claim 26 wherein said growth factor-secreting cell comprises a xenograft.

32. The device of claim 26 wherein said growth factor-secreting cell comprises a murine submaxillary gland cell.

33. The therapy device of claim 26 wherein said growth factor-secreting cell has been genetically engineered to produce said growth factor.