Reticulated elastomeric matrices, their manufacture and use in implantable devices

• US 20050043816A1
• Filed: 05/17/2004
• Published: 02/24/2005
• Est. Priority Date: 05/15/2003
• Status: Active Grant

• Current Assignee: DSM IP Assets BV (DSM-Firmenich AG)
• Original Assignee: Biomerix Corp.
• Inventors: Friedman, Craig, Klempner, Daniel, Datta, Arindam, Sendijarevic, Aisa
• Granted Patent: US 7,803,395 B2
• Time in Patent Office: Days
• US Class Current: 623/23.610
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: Y10T 428/24512 Polyurethane
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]

Abstract

This invention relates to biodurable, reticulated elastomeric matrices that are resiliently-compressible, their manufacture and uses including uses for implantable devices into or for topical treatment of patients, such as humans and other animals, for therapeutic, nutritional, or other useful purposes.

Claims

1. An implantable device comprising a reticulated resiliently-compressible elastomeric matrix.

2. The implantable device of claim 1, wherein the implantable device is biodurable for at least 29 days.

3. The implantable device of claim 1, wherein the elastomeric matrix comprises a polycarbonate polyurethane.

4. The implantable device of claim 3, wherein the implantable device is biodurable for at least 6 months.

5. The implantable device of claim 1, wherein the elastomeric matrix comprises a polycarbonate urea-urethane.

6. The implantable device of claim 5, wherein the implantable device is biodurable for at least 6 months.

7. The implantable device of claim 1, comprising a reticulated elastomeric matrix comprising a plurality of pores, the pores having an average diameter or other largest transverse dimension of at least about 20 μ

m.

8. The implantable device of claim 7, wherein the pores have an average diameter or other largest transverse dimension of from about 20 μ

m to about 150 μ

m.

9. The implantable device of claim 1, comprising a reticulated elastomeric matrix comprising a plurality of pores, the pores having an average diameter or other largest transverse dimension of from about 150 μ

m to about 250 μ

m.

10. The implantable device of claim 1, comprising a reticulated elastomeric matrix comprising a plurality of pores, the pores having an average diameter or other largest transverse dimension of from about 250 μ

m to about 600 μ

m.

11. The implantable device of claim 10, comprising a reticulated elastomeric matrix comprising a plurality of pores, the pores having an average diameter or other largest transverse dimension of from greater than 250 μ

m to about 500 μ

m.

12. The implantable device of claim 1, comprising a resiliently-compressible elastomeric matrix such that the implantable device, when compressed from a relaxed configuration to a first, compact configuration for delivery via a delivery-device, expands to a second, working configuration, in vitro, at least about 80% of the size of the relaxed configuration in at least one dimension.

13. The implantable device of claim 12, wherein the recovery properties of the elastomeric matrix are such that a dimension of the second, working configuration is within about 20% of a relaxed dimension of the relaxed configuration after compression to from about 50 to about 10% of the relaxed dimension and wherein the elastomeric matrix has a compressive strength at 50% compression of from about 1 to about 500 psi (from about 700 kg/m² to about 350,000 kg/m²), a tensile strength of from about 1 to about 500 psi (from about 700 kg/m² to about 350,000 kg/m²), and an ultimate tensile elongation of at least about 25%.

14. The implantable device of claim 1, wherein the elastomeric matrix has a compression set after 22 hours compression at about 25°

C. to 25% of its thickness in one dimension of not more than about 30%.

15. The implantable device of claim 1, wherein the elastomeric matrix, present in a first, compact configuration that is achieved by applying about 75% compression strain to the elastomeric matrix for up to 10 minutes, recovers to a second, working configuration having about 90% of a pre-compression dimension the of elastomeric matrix in 30 seconds or less.

16. The implantable device of claim 15, wherein the recovery is in 20 seconds or less.

17. The implantable device of claim 1, wherein the elastomeric matrix, present in a first, compact configuration that is achieved by applying about 75% compression strain to the elastomeric matrix for up to 30 minutes, recovers to a second, working configuration having about 90% of a pre-compression dimension the of elastomeric matrix in 120 seconds or less.

18. The implantable device of claim 17, wherein the recovery is in 60 seconds or less.

19. The implantable device of claim 17, wherein the recovery is in 30 seconds or less.

20. The implantable device of claim 1, wherein the elastomeric matrix, present in a first, compact configuration that is achieved by applying about 75% compression strain to the elastomeric matrix for up to 30 minutes, recovers to a second, working configuration having about 97% of the pre-compression volume of the elastomeric matrix in 10 minutes or less.

21. The implantable device of claim 1, wherein the elastomeric matrix comprises polycarbonate, polyester, polyether, polysiloxane, polyurethane, or a mixture thereof.

22. The implantable device of claim 1, wherein the reticulated elastomeric matrix is configured to permit cellular ingrowth and proliferation into the elastomeric matrix.

37. A method of treating an orthopedic disorder, the method comprising:

a) compressing the implantable device of claim 1 from a relaxed configuration to a first, compact configuration;

b) delivering the compressed implantable device to the in vivo site of the orthopedic disorder via a delivery-device; and

c) allowing the implantable device to expand to a second, working configuration at the in vivo site.

38. The method of claim 37, wherein the implantable device comprises a plurality of elastomeric matrices.

39. A method of treating an orthopedic disorder, the method comprising inserting the implantable device of claim 1 by an open surgical procedure.

23. A lyophilization process for producing an elastomeric matrix having a reticulated structure, the process comprising:

a) forming a solution comprising a solvent-soluble biodurable elastomer in a solvent;

b) at least partially solidifying the solution to form a solid, optionally by cooling the solution; and

c) removing the non-polymeric material, optionally by subliming the solvent from the solid under reduced pressure, to provide an at least partially reticulated elastomeric matrix comprising the elastomer.

24. The process of claim 23, wherein the elastomer is a thermoplastic elastomer selected from polycarbonate polyurethanes, polyester polyurethanes, polyether polyurethanes, polysiloxane polyurethanes, polyurethanes with mixed soft segments, or a mixture thereof.

25. A polymerization process for preparing a reticulated elastomeric matrix, the process comprising admixing:

a) a polyol component,

b) an isocyanate component,

c) a blowing agent,

d) optionally, a crosslinking agent or a chain extender,

e) optionally, a chain extender,

f) optionally, at least one catalyst,

g) optionally, at least one cell opener,

h) optionally, a surfactant, and

i) optionally, a viscosity modifier;

to provide a crosslinked elastomeric matrix reticulating the elastomeric matrix by a reticulation process to provide the reticulated elastomeric matrix.

26. The process of claim 25, wherein the polyol component comprises a polycarbonate polyol, hydrocarbon polyol, polysiloxane polyol, poly(carbonate-co-hydrocarbon) polyol, poly(carbonate-co-siloxane) polyol, poly(hydrocarbon-co-siloxane) polyol, or a mixture thereof.

27. The process of claim 26, wherein the polyol component comprises a difunctional polycarbonate diol.

28. The process of claim 25, wherein the isocyanate component comprises tetramethylene diisocyanate, cyclohexane-1,2-diisocyanate, cyclohexane-1,4-diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate, methylene-bis-(p-cyclohexyl isocyanate), p-phenylene diisocyanate, 4,4′

-diphenylmethane diisocyanate, 2,4′

-diphenylmethane diisocyanate, 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, m-tetramethylxylene diisocyanate, or a mixture thereof.

29. The process of claim 25, wherein the isocyanate component comprises MDI, wherein the MDI is a mixture of at least about 5% by weight of 2,4′

-MDI with the balance 4,4′

-MDI.

30. The process of claim 28, wherein the average number of isocyanate groups per molecule in the isocyanate component is about 2.

31. The process of claim 28, wherein the average number of isocyanate groups per molecule in the isocyanate component is greater than 2.

32. The process of claim 28, wherein the isocyanate component has an isocyanate index and wherein the isocyanate index is from about 0.9 to about 1.1.

33. The process of claim 32, wherein the isocyanate component has an isocyanate index and wherein the isocyanate index is from about 0.98 to about 1.02.

34. A process for preparing a reticulated composite elastomeric implantable device, the process comprising endoporously coating a reticulated elastomeric matrix with a coating material selected to encourage cellular ingrowth, cellular proliferation or a mixture thereof.

35. The process of claim 34, wherein the coating material comprises a foamed coating of a biodegradable material, the biodegradable material comprising collagen, fibronectin, elastin, hyaluronic acid or a mixture thereof.

36. The process of claim 35, wherein the coating material comprises a collagen.