US4892538A
Expired / Lapsed
US
⏱️ 0.0 years remaining
In vivo delivery of neurotransmitters by implanted, encapsulated cells
Assignee: BROWN UNIVERSITY RESEARCH FOUNDATION BROWN UNIVERSITY PROVIDENCE RI A CORP OF RHODE ISLAND
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Filing: 1987-11-17
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Granted: 1990-01-09
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Expires: 2007-11-17
Abstract
Abstract Methods and devices are disclosed for the delivery of a neurotransmitter from an implanted, neurotransmitter-secreting cell culture to a target region in a subject. The cell culture is maintained within a biocompatible, semipermeable membrane which permits the diffusion of the neurotransmitter therethrough while excluding viruses, antibodies, and other detrimental agents present in the external environment from gaining access. Implantable cell culture devices are disclosed, some of which may be retrieved from the subject, replaced or recharged with new, neurotransmitter-secreting cell cultures, and reimplanted.
Inventors
- 👤 Patrick Aebischer
- 👤 Shelley R. Winn
- 👤 Pierre M. Galletti
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 23:02
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0087; A61K9/0092; A61K9/20; A61F; A61F2/00; A61F2/02; A61F2/022; A61K35/00; A61K35/12; A61K35/22; A61K35/30; A61K9/0012; A61K9/0019; A61K9/0024; A61K9/0085; A61K9/48; A61K9/50; A61M; A61M31/00; A61M31/002; B; B01; B01J; B01J13/00; B01J13/02; C; C12; C12N; C12N11/00; C12N11/02; C12N11/04; C12N5/00; C12N5/0012; C12N5/06; C12N5/0602; C12N5/0613; C12N5/0614; C12N5/0618; C12N5/0619; A61M2210/00; A61M2210/06; A61M2210/0687; A61M2210/0693; C12N2533/00; C12N2533/30
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
87 words
A method of delivering a neurotransmitter to a subject afflicted with a neurotransmitter deficiency comprising the steps of: encapsulating at least one neurotransmitter-secreting cell within a semipermeable membrane, said membrane allowing the diffusion of the neurotransmitter therethrough while excluding viruses, antibodies and other detrimental agents present in the external environmental; and implanting said encapsulated cell into a target region within a subject's brain, such that the encapsulated cell secretes the neurotransmitter and thereby provide constitutive delivery of the neurotransmitter to the target region to treat the deficiency.
Claim 2
Independent Claim
87 words
A method of delivering a neurotransmitter to a subject afflicted with a neurotransmitter deficiency comprising the steps of: encapsulating at least one neurotransmitter-secreting cell within a semipermeable membrane, said membrane allowing the diffusion of the neurotransmitter therethrough while excluding viruses, antibodies and other detrimental agents present in the external environmental; and implanting said encapsulated cell into a target region within a subject's brain, such that the encapsulated cell secretes the neurotransmitter and thereby provide constitutive delivery of the neurotransmitter to the target region to treat the deficiency.
Claim 3
Dependent Claim
37 words
The method of claim 1 wherein said encapsulating step further comprises disposing said neurotransmitter-secreting cell within said semipermeable membrane, said membrane allowing the diffusion of solutes having a molecular weight of up to about 50,000 daltons therethrough.
Claim 4
Dependent Claim
50 words
The method of claim 1 wherein said encapsulating step further comprises disposing said neurotransmitter-secreting cell within, said semipermeable membrane, said membrane being composed of a material selected from the group consisting of acrylic copolymers, polyvinylidene fluoride, polyurethane isocyanates, polyalginate, cellulose acetate, polysulfone, polyvinyl alcohols, polyacrylonitrile, and derivatives and mixtures thereof.
Claim 5
Dependent Claim
33 words
The method of claim 1 wherein said implanting step is reversible, said semipermeable membrane being attached to a retrievable, nonresorpable, and biocompatible guide wire which enables removal of said device from said subject.
Claim 6
Dependent Claim
53 words
The method of claim 4 wherein said encapsulating step further comprises disposing said neurotransmitter-secreting cell within said membrane in a retrievable fashion, said membrane having a tubular shape with a first end and a second end, said ends each having a cap element removably attached thereto to enable extraction of said cells therein.
Claim 7
Dependent Claim
43 words
The method of claim 1 wherein said encapsulating step further comprises disposing within said membrane a neurotransmitter-secreting cell, said neurotransmitter being dopamine, and said neurotransmitter-secreting cell being selected from the group consisting of adrenal medulla tissue, ventral mesencephalic embryonic tissue, and neuroblastoid tissue.
Claim 8
Dependent Claim
39 words
The method of claim 1 wherein said encapsulating step further comprises disposing within said membrane a cell which secretes one of the group consisting of a precursor, analog, agonist, derivative, and fragment of a neurotransmitter which has neurotransmitter activity.
Claim 9
Dependent Claim
15 words
The method of claim 7 wherein said neurotransmitter is dopamine, and said precursor is L-dopa.
Claim 10
Dependent Claim
15 words
The method of claim 7 wherein said neurotransmitter is dopamine, and said analog is bromocriptine.
Claim 11
Dependent Claim
24 words
The method of claim 1 wherein said encapsulating step further comprises disposing within said membrane a neurotransmitter-secreting cell, said cell being a tissue allograft.
Claim 12
Dependent Claim
24 words
The method of claim 1 wherein said encapsulating step further comprises disposing within said membrane a neurotransmitter-secreting cell, said cell being a tissue xenograft.
Claim 13
Dependent Claim
29 words
The method of claim 1 wherein said implanting step further comprises implanting said encapsulated, neurotransmitter-secreting cell in said target region of said subject, said target region being the brain.
Claim 14
Dependent Claim
74 words
A cell culture device for implantation within a subject for the constitutive delivery of a neurotransmitter to a target area of said subject, said device comprising: a semipermeable membrane permitting the diffusion of the neurotransmitter therethrough, while excluding viruses, antibodies, and other detrimental agents present in the external environment; and at least one neurotransmitter-secreting cell disposed within the membrane, said cell being capable of secreting neurotransmitter without direct neuronal contact with said target area.
Claim 15
Dependent Claim
74 words
A cell culture device for implantation within a subject for the constitutive delivery of a neurotransmitter to a target area of said subject, said device comprising: a semipermeable membrane permitting the diffusion of the neurotransmitter therethrough, while excluding viruses, antibodies, and other detrimental agents present in the external environment; and at least one neurotransmitter-secreting cell disposed within the membrane, said cell being capable of secreting neurotransmitter without direct neuronal contact with said target area.
Claim 16
Dependent Claim
23 words
The device of claim 14 wherein said semipermeable membrane is permeable to solutes having a molecular weight of up to about 50,000 daltons.
Claim 17
Dependent Claim
36 words
The device of claim 14 wherein said semipermeable membrane comprises a material selected from the group consisting of acrylic copolymers, polyvinylidene fluoride, polyurethane isocyanates, polyalginate, cellulose acetate, polysulfone, polyvinyl alcohols, polyacrylonitrile, and derivatives and mixtures thereof.
Claim 18
Dependent Claim
14 words
The device of claim 14 wherein said neurotransmitter-producing cell further comprises a tissue allograft.
Claim 19
Dependent Claim
14 words
The device of claim 14 wherein said neurotransmitter-producing cell further comprises a tissue xenograft.
Claim 20
Dependent Claim
31 words
The device of claim 14 wherein said neurotransmitter is dopamine, and said neurotransmitter-secreting cell is selected from the group consisting of adrenal medulla tissue, ventral mesencephalic embryonic tissue, and neuroblastoid tissue.
Claim 21
Dependent Claim
28 words
The device of claim 14 wherein said neurotransmitter is selected from the group consisting of agonists, precursors, analogs, derivatives, and fragments of a neurotransmitter which have neurotransmitter activity.
Claim 22
Dependent Claim
11 words
The device of claim 19 wherein said neurotransmitter precursor is L-dopa.
Claim 23
Dependent Claim
11 words
The device of claim 19 wherein said neurotransmitter analog is bromocriptine.
Claim 24
Dependent Claim
31 words
The device of claim 14 further comprising a retrievable, nonresorpable, and biocompatible guide wire attached to said semipermeable membrane, so as to enable the removal of said device from said subject.
Claim 25
Dependent Claim
23 words
The device of claim 14 wherein said semipermeable membrane is tubular, having at least one end with a cap element reversibly attached thereto.
Claim 26
Dependent Claim
44 words
The device of claim 22 wherein said neurotransmitter-secreting cell is disposed within said semipermeable membrane in a removable fashion, said membrane being tubular, having at least one end with a cap element reversibly attached thereto, so as to enable extraction of said cells therein.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-01-08 | 1993-07-10 | 1994-01-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-01-08 | 1997-07-10 | 1998-01-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-01-08 | 2001-07-10 | 2002-01-09 | $7700.00 | Window Closed / Lapsed |