Device for delivery of substances and methods of use thereof

• US 5,681,568 A
• Filed: 08/19/1994
• Issued: 10/28/1997
• Est. Priority Date: 08/19/1994
• Status: Expired due to Fees

• Current Assignee: CeNeS Pharmaceuticals, Inc. (PAION AG)
• Original Assignee: CeNeS Pharmaceuticals, Inc. (PAION AG)
• Inventors: Sudhalter, Judith, Fine, Eric, Mahanthappa, Nagesh K., Goldin, Stanley M.
• Primary Examiner(s): Hutzell, Paula K.
• Assistant Examiner(s): MINNIFIELD, NITA M
• Application Number:
  US08/293,465
• Time in Patent Office: 1,166 Days
• Field of Search: 424/184.1, 424/423, 424/468, 424/472, 424/486 T, 424/DIG. 7, 424/424, 424/443, 424/449, 264/41, 264/216, 604/890 T, 530/399, 514/2, 514/12, 514/14
• US Class Current: 424/184.1
• CPC Class Codes: A61B 17/1128 of nerves
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1883 Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
• 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: A61L 2300/214 Amino acids
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y10S 424/07 Microporous membranes

Abstract

This invention comprises devices and methods for producing a composite microporous membrane specifically tailored to be useful for optimizing the delivery of macromolecules to a therapeutic target.

Claims

1. A device comprising a microporous underlayment with microcapillary pores wherein said pores are coated but not completely filled by a microskin to which a biologically active macromolecular agent is bound.

3. The device of claim 1 wherein said microporous underlayment comprises a polymer.

4. The device of claim 3 wherein said polymer comprises one or more monomers selected from the group consisting of an olefin, amide, carbonate, ester, styrene, sulphone, imide, vinyl chloride, aldehyde, arylate, haloolefin acetyl, acrylate, urethane, vinylidine fluoride, vinylidine chloride, cellulose esters or cellulose, lactide, anhydride, glycolide, saccharide and amino acids.

5. The device of claim 1 wherein said microskin comprises a substance capable of binding to said underlayment and binding said macromolecule in a manner enabling subsequent controlled release of said biologically active macromolecular agent.

6. The device of claim 5 wherein said microskin comprises one or more substances selected from the group consisting of collagens, fibronectins, laminins, proteoglycans, glycolipids and glycosaminoglycans.

7. The device of claim 5 wherein said microskin comprises a synthetic polymer of one or more monomers selected from the group of olefin, amide, carbonate, ester, styrene, sulphone, imide, vinyl chloride, aldehyde, arylate, haloolefin acetyl, acrylate, urethane, vinylidene fluoride, vinylidene chloride, cellulose esters, lactide, anhydride, glycolide, saccharide and amino acids.

8. The device of claim 1 wherein said biologically active macromolecular agent is comprised of amino acids or amino acid derivatives.

9. The device of claim 1 wherein said biologically active macromolecular agent binds to said microskin by cooperative non-covalent binding.

10. The device of claim 1 wherein said underlayment, said microskin and said biologically active macromolecular agent are biodegradable.

11. The device of claim 1 wherein said device is of a size and shape suitable for placement in an environment of use.

12. The device of claim 11 wherein said shape is selected from the group consisting of cylindrical, bullet, elliptical, circular, bulbous, loop, bow, ellipsoid, hollow cylindrical, rectangular, doughnut and crescent.

14. A method for controlled delivery of a biologically active macromolecular agent comprising placement of the device of claim 1 in an environment of use.

15. The method of claim 14 wherein said environment of use is a mammalian body.

16. A method of treatment or therapy for a subject with a disorder or susceptibility to a disorder comprising placement of the device of claim 1 in said subject.

17. The method of claim 16 wherein said placement of the device is proximate to a therapeutic target within said subject for said treatment or therapy.

18. The method of claim 16 wherein said disorder comprises traumatic injury.

20. A method for making the device of claim 1 comprising the steps of:

a) fabricating the microporous underlayment with microcapillary pores;

b) coating but not completely filling said pores of the microporous underlayment with a microskin; and

c) binding the biologically active macromolecular agent to the microskin.

2. A device comprising a microporous underlayment with microcapillary pores wherein said pores are coated but not completely filled by a microskin to which a biologically active macromolecular agent is bound and is releasable therefrom.

13. A device comprising a microporous underlayment with microcapillary pores comprised of cellulose, wherein said pores are coated but not completely filled by a microskin comprised of collagen to which glial growth factor 2 is bound and is releasable therefrom.

19. A method of treatment or therapy involving nerve regeneration for a human disorder comprising placement of the device of claim 13 proximate to a site of said nerve regeneration.