Implantable device and uses therefor

• US 5,911,704 A
• Filed: 08/20/1997
• Issued: 06/15/1999
• Est. Priority Date: 06/05/1995
• Status: Expired due to Term

• Current Assignee: Renamed Biologics, Inc.
• Original Assignee: Nephros Therapeutics, Inc. (Renamed Biologics, Inc.)
• Inventors: Humes, H. David
• Primary Examiner(s): Coggins, Wynn Wood
• Assistant Examiner(s): Blyveis, Deborah
• Application Number:
  US08/915,033
• Time in Patent Office: 664 Days
• Field of Search: 604/890.1, 604/891.1, 604/93, 604/264, 604/52, 604/198, 604/200
• US Class Current: 604/93.01
• CPC Class Codes: A61F 2/0105 Open ended, i.e. legs gathered only at one side
• 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: A61F 2002/016 made from wire-like elements
• CPC Class Codes: A61F 2230/005 Rosette-shaped, e.g. star-shaped
• CPC Class Codes: A61F 2230/0067 conical
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: 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

Abstract

Disclosed is an implantable device for delivering a pre-selected molecule, for example, a hormone, into a mammal'"'"'s systemic circulation. The device comprises a blood permeable element that can be anchored to an inner wall of an intact blood vessel. The device also comprises a capsule that is held in place within the blood vessel by the anchored blood permeable element. The capsule encloses viable cells which produce and secrete the preselected molecule into blood passing the capsule. The invention also provides a minimally invasive method for percutaneously introducing into a preselected blood vessel the device of the invention.

Claims

1. An implantable device for delivering a pre-selectd molecule into systemic circulation, the device comprising in combination:

(a) a blood permeable element comprising at least one metallic filament anchorable to an inner wall of a blood vessel which when anchored to the inner wall of the vessel permits blood in the vessel to pass therethrough; and

(b) a capsule having disposed therein viable cells which produce and secrete the pre-selected molecule, wherein the capsule, when introduced into the vessel, is retained within the vessel by the blood permeable element and the cells disposed therein produce and secrete the pre-selected molecule into blood passing the capsule.

2. The device of claim 1, wherein the blood permeable element is an embolism anti-migration filter.

3. The device of claim 1, wherein the capsule when introduced into the vessel is retained upstream of the blood permeable element.

4. The device of claim 1, wherein the capsule comprises at least one hollow fiber.

5. The device of claim 4, wherein the hollow fiber is defined by a semi-permeable membrane.

6. The device of claim 5, wherein the semi-permeable membrane defines pores of a size sufficient to permit diffusion of the pre-selected molecule therethrough but insufficient to permit diffusion of the cells therethrough.

7. The device of claim 5 or 6, wherein the pores are dimensioned to exclude an agent in the blood which is detrimental to cell viability.

8. The device of claim 7, wherein the pores are dimensioned to prevent passage of antibodies therethrough.

9. The device of claim 5, wherein the semi-permeable membrane defines pores which permit solutes less than 150 kD to pass therethrough.

10. The device of claim 5, wherein the semi-permeable membrane comprises a material selected from the group consisting of polyvinylchloride, polyvinylidene fluoride, polyurethane isocyanate, polyalginate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose nitrate, polysulfone, polystyrene, polyurethane, polyvinyl alcohol, polyacrylonitrile, polyamide, polymethylmethacrylate, polyethylene oxide, polytetrafluorethylene, and mixtures thereof.

11. The device of claim 1, wherein the cells are eukaryotic cells.

12. The device of claim 11, wherein in the cells are mammalian cells.

13. The device of claim 1, wherein the cells are genetically engineered cells.

14. The device of claim 1, wherein the pre-selected molecule is a protein.

15. The device of claim 14, wherein the pre-selected molecule is a hormone.

16. The device of claim 15, wherein the hormone is selected from the group consisting of erythropoietin and insulin.

17. The device of claim 1, wherein the cells produce a plurality of pre-selected molecules.

18. The device of claim 1, wherein the cells produce the pre-selected molecule in response to a stimulus in the blood.

19. The device of claim 1, wherein the cells constitutively produce the pre-selected molecule.

20. The device of claim 1, wherein the blood permeable element comprises a plurality of metallic filaments anchorable to the inner wall of the vessel.

21. The device of claim 1, filter comprising a second blood permeable element anchorable to the inner wall of the vessel, wherein the second blood permeable element, when introduced into the vessel retains the capsule within the vessel.

22. An implantable device for delivering erythropoietin into mammalian circulation, the device comprising in combination:

(a) a filter anchorable to an inner wall of a blood vessel which when anchored to the inner wall of the vessel permits blood in the vessel to pass therethrough; and

(b) a capsule having disposed therein viable cells which produce and secrete erythropoietin wherein the capsule, when introduced into the vessel, is retained within the vessel by the filter and the cells disposed therein produce and secrete the erythropoietin into blood passing the capsule.

23. The device of claim 22, wherein the cells produce erythropoietin in response to a stimulus.

24. The device of claim 23, wherein the cells produce erythropoietin in response to reduced oxygen carrying capacity of the blood.

25. The device of claim 22, wherein the filter comprises a metallic filament anchorable to the inner wall of the blood vessel.

30. The device of claim 22 or 26, wherein the capsule comprises at least one hollow fiber.

31. The device of claim 30, wherein the hollow fiber is defined by a semi-permeable membrane.

32. The device of claim 31, wherein the semi-permeable membrane defines pores of a size dimensioned to minimize passage therethrough of an agent in the blood detrimental to the viability of the cells.

33. The device of claim 22 or 26, wherein the cells are eukaryotic cells.

34. The device of claim 33, wherein the cells are mammalian cells.

35. The device of claim 22 or 26, wherein the capsule when introduced into the vessel is retained upstream of the filter.

26. An implantable device for delivering insulin into mammalian circulation, the device comprising:

(a) a filter anchorable to an inner wall of a blood vessel which when anchored to the inner wall of the vessel permits blood in the vessel to pass therethrough; and

(b) a capsule having disposed therein viable cells which produce and secrete insulin, wherein the capsule, when introduced into the vessel, is retained within the vessel by the filter and the cells disposed therein produce and secrete the insulin into blood passing the capsule.

27. The device of claim 26, wherein the cells produce insulin in response to a stimulus.

28. The device of claim 27, wherein the cells produce insulin in response to the level of glucose in the blood.

29. The device of claim 26, wherein the filter comprises a metallic filament anchorable to the inner wall of the blood vessel.

36. An implantable device for delivering a pre-selected molecule into systemic circulation, the device comprising in combination:

(a) a blood permeable element comprising a head and a plurality of legs extending therefrom anchorable to an inner wall of a blood vessel which when anchored to the inner wall of the blood vessel permits blood in the vessel to pass therethrough; and

(b) a capsule having disposed therein viable cells which produce and secrete the pre-selected molecule, wherein the capsule, when introduced into the vessel, is retained within the vessel by the blood permeable element and the cells disposed herein produce and secrete the pre-selected molecule into blood passing the capsule.

37. The device of claim 36, wherein the blood permeable element is an embolism antimigration filter.

38. The device of claim 36, wherein the capsule comprises at least one hollow fiber.

39. The device of claim 38, wherein the hollow fiber is defined by a semi-permeable membrane.

40. The device of claim 39, wherein the semi-permeable membrane defines pores of a size sufficient to permit diffusion of the pre-selected molecule therethrough but insufficient to permit diffusion of the cells therethrough.

41. The device of claim 36, wherein the cells are eukaryotic cells.

42. The device of claim 41, wherein the cells are mammalian cells.

43. The device of claim 36, wherein the pre-selected molecule is a protein.

44. The device of claim 43, wherein the protein is a hormone.

45. The device of claim 44, wherein the pre-selected molecule is selected from the group consisting of insulin and erythropoietin.

46. The device of claim 36, wherein the blood permeable element is metallic.

47. The device of claim 36, further comprising a second blood permeable cement anchorable to the inner wall of the vessel, wherein the second blood permeable element, when introduced into the vessel retains the capsule within the vessel.