Methods for treating diabetes by delivering insulin from biocompatible cell-containing devices

• US 5,869,077 A
• Filed: 05/24/1995
• Issued: 02/09/1999
• Est. Priority Date: 04/25/1991
• Status: Expired due to Term

• Current Assignee: Neurotech S.A. (LivaNova Plc)
• Original Assignee: Brown University
• Inventors: Emerich, Dwaine F., Aebischer, Patrick, Sanberg, Paul R., Dionne, Keith E., Lysaght, Michael J., Vasconcellos, Alfred V., Gentile, Frank T., Christenson, Lisa, Scharp, David W., Hegre, Orion D., Hoffman, Diane, Lacy, Paul E.
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US08/449,562
• Time in Patent Office: 1,357 Days
• Field of Search: 424/422, 424/426, 424/423, 424/424, 424/490, 514/866
• US Class Current: 424/422
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• 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 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: C12N 2510/02 : Cells for production
• CPC Class Codes: C12N 5/0012 : Cell encapsulation
• CPC Class Codes: C12N 5/0062 : General methods for three-dimensional culture
• CPC Class Codes: C12N 5/0614 : Adrenal gland
• CPC Class Codes: C12N 5/0656 : Adult fibroblasts
• CPC Class Codes: C12N 5/0677 : Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

A method for treating diabetes in a patient comprising subcutaneously implanting in the patient at least one immunoisolatory vehicle comprising a core comprising a volume of at least 1 μl and at least about 10⁴ living cells which secrete insulin, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and a surrounding external jacket of a biocompatible thermoplastic or hydrogel free of said cells projecting externally thereof, said jacket being permselective and immunoisolatory, said jacket having a molecular weight cutoff permitting passage of molecules between the patient and core through said jacket wherein the insulin is released from the immunoisolatory vehicle into the patient'"'"'s body to treat diabetes.

Claims

1. A method for treating diabetes in a patient comprising subcutaneously implanting in the patient at least one immunoisolatory vehicle comprising:

(a) a core comprising a volume of at least 1 μ

l and at least about 10⁴ living cells which secrete insulin, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and

(b) a surrounding external jacket of a biocompatible thermoplastic or hydrogel free of said cells projecting externally thereof, said jacket being permselective and immunoisolatory, said jacket having a molecular weight cutoff permitting passage of molecules between the patient and core through said jacket wherein the insulin is released from the immunoisolatory vehicle into the patient'"'"'s body to treat diabetes.

2. The method of claim 1 wherein the core matrix comprises a hydrogel.

3. The method of claim 1 wherein the core matrix is selected from the group consisting of alginate, collagen, laminin-containing hydrogels, agarose, cellulose, methylcellulose, block copolymer of ethylene-vinylalcohol, sodium polystyrene sulfonate, vinyl-methyl-tribenzyl ammonium chloride, phosphazene, and polyvinylalcohol.

4. The method of claim 1 wherein the core matrix is selected from the group consisting of collagen laminin, glycoaminoglycans, proteoglycans, fibronectin, elastin, and mixtures thereof.

5. The method of claim 1 wherein the jacket comprises a thermoplastic.

6. The method of claim 1 wherein the jacket is selected from the group consisting of polyacrylonitrile-polyvinylchloride, polyacrylonitrile, polymethylmethacrylate, polyvinyldifluoride, polyolefins, polysulfones and celluloses.

7. The method of claim 1 wherein the jacket further comprises a hydrophilic or hydrophobic additive.

8. The method of claim 1 wherein the jacket is between 5 and 200 μ

m thick.

9. The method of claim 1 wherein the jacket has a molecular weight cutoff between 50 kD and 2000 kD.

10. The method of claim 1 wherein the jacket is shaped to form a hollow fiber.

11. The method of claim 1 wherein the jacket is shaped to form a flat sheet.

12. The method of claim 1 wherein more than one vehicle but fewer than 10 vehicles are implanted in the patient.

13. The method of claim 1 wherein the cells are allogeneic or syngeneic to the patient.