At least partially resorbable reticulated elastomeric matrix elements and methods of making same

• US 9,050,176 B2
• Filed: 01/17/2012
• Issued: 06/09/2015
• Est. Priority Date: 04/03/2009
• Status: Active Grant

• Current Assignee: DSM IP Assets BV (DSM-Firmenich AG)
• Original Assignee: Biomerix Corp.
• Inventors: Datta, Arindam, Friedman, Craig, Haridas, Balakrishna, Lavelle, Lawrence P.
• Primary Examiner(s): MCEVOY, THOMAS M
• Application Number:
  US13/352,276
• Publication Number:
  US 20120239161A1
• Time in Patent Office: 1,239 Days
• Field of Search: 623/1.36, 623/1.39, 623/1.4, 623/1.41, 623/1.46, 623/1.49, 623/11.11, 623/14.12, 623/15.12, 623/23.72, 623/23.75, 623/23.76, 424/422, 424/424, 424/425, 52/50, 52/52, 521/17, 521/70, 521/72, 521/73
• US Class Current: 1/1
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 2430/10 for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08G 18/1833 having ether, acetal, or orthoester groups
• CPC Class Codes: C08G 18/2063 having two nitrogen atoms in the condensed ring system
• CPC Class Codes: C08G 18/3206 aliphatic
• CPC Class Codes: C08G 18/4277 Caprolactone and/or substituted caprolactone
• CPC Class Codes: C08G 18/6611 having at least three hydroxy groups
• CPC Class Codes: C08G 18/7671 containing only one alkylene bisphenyl group
• CPC Class Codes: C08G 2110/0058 ≥50 and <150kg/m3
• CPC Class Codes: C08G 2110/0083 prepared using water as the sole blowing agent
• CPC Class Codes: C08G 2230/00 Compositions for preparing biodegradable polymers
• CPC Class Codes: C08L 101/16 the macromolecular compounds being biodegradable
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

The present disclosure relates to reticulated elastomeric matrices, and more particularly to at least partially degradable elastomeric elements that are compressible and exhibit resilience in their recovery and that can be employed in diverse applications including, without limitation, biological implantation, especially in humans.

Claims

1. A reticulated matrix comprising (a) a soft segment comprising a polycaprolactone copolymer polyol and (b) a hard segment comprising an isocyanate having cross-linking and optionally having a chain extender, the reticulated matrix having a continuous-interconnected void phase, wherein the reticulated matrix is configured to be implantable and at least partially degradable, wherein the continuous-interconnected void phase extends from an interior portion to an exterior surface of said matrix;

wherein a path through the void phase can be drawn in a substantially linear direction across an entirety of said matrix beginning at any portion of an exterior surface of said matrix containing said void phase.

2. The reticulated matrix of claim 1, wherein the reticulated matrix is substantially fully degradable.

3. The reticulated matrix of claim 1, wherein the reticulated matrix comprises a cross-linked polycaprolactone polyurethane-urea or a polycaprolactone polyurethane.

4. The reticulated matrix of claim 1, wherein the hard segment comprises aromatic and/or aliphatic isocyanate and the soft segment comprises polyester polyol, polycaprolactone polyol, a poly(caprolactone-co-glycolide)polyol, a poly(caprolactone-co-l-lactide) polyol, a poly(caprolactone-co-d-l-lactide)polyol, poly(caprolactone-co-paradioxanone polyol poly(caprolactone-co-glycolide-co-lactide)polyol, poly(caprolactone-co-glycolide-co-d/l lactide)polyol, poly(caprolactone-co-lactide-co-d/lactide)polyol, a poly(caprolactone-co-polyethylene glycolide)polyol or their appropriate combinations.

5. The reticulated matrix of claim 1, wherein the reticulated matrix comprises a reticulated, resiliently-compressible, elastomeric matrix that promotes tissue ingrowth and comprises a continuous network of intercommunicating and inter-connected solid void space, wherein said void space comprises a plurality of interconnected cells and pores that are fully accessible.

6. The reticulated matrix of claim 1, wherein the reticulated matrix is biocompatible and conducive to allow for fluid transfer, tissue ingrowth, regeneration and re- modeling with bio-integration to wound or defect site to heal tissue defect.

7. The reticulated matrix of claim 1, wherein hydrolytic of the reticulated matrix degradation rates are controllable through multiple different mechanisms.

8. The reticulated matrix of claim 1, wherein hydrolytic of the reticulated matrix are controllable by the composition of polyol-derived soft segments, molecular weight of the polyol-derived soft segments, relative molecular weights of the copolymers of the polyol-derived soft segments, degree and extent of cross-linking, degree and extent of chain extension, application of gamma sterilization or combinations thereof.

9. A process of making a reticulated matrix comprising a foaming by reacting isocyanate with polyol in presence of a blowing agent to form a porous reaction product, and thermally reticulating of the porous matrix to form the reticulated matrix, wherein the reticulated matrix is configured to be implantable and at least partially degradable wherein the reticulated matrix having a continuous-interconnected void phase, wherein the continuous-interconnected void phase extends from an interior olio to an exterior surface of said matrix;

wherein a path through the void phase can be drawn in a substantially linear direction across an entirety of said matrix beginning at any portion of an exterior surface of said matrix containing said void phase.

10. The process of claim 9, wherein the foaming comprises reacting (a) a soft segment comprising a polycaprolactone copolymer polyol and (b) a hard segment comprising an isocyanate having cross-linking and optionally having a chain extender.

11. The process of claim 9, wherein the reticulated matrix comprises a cross-linked polycaprolactone polyurethane-urea or a polycaprolactone polyurethane.

12. The process of claim 11, wherein the hard segment comprises aromatic and/or aliphatic isocyanate and the soft segment comprises polyester polyol, polycaprolactone polyol, a poly(caprolactone-co-glycolide)polyol, a poly(caprolactone-co-l-lactide)polyol, a poly(caprolactone-co-d-l-lactide)polyol, poly(caprolactone-co-paradioxanone polyol poly(caprolactone-co-glycolide-co-lactide)polyol, poly(caprolactone-co-glycolide-co-d/l lactide)polyol, poly(caprolactone-co-lactide-co-d/l lactide)polyol, a poly(caprolactone-co-polyethylene glycolide)polyol or their appropriate combinations.

13. The process of claim 9, wherein during the foaming, gelation occurs such that the porous reaction product has dimension structural stability.

14. The process of claim 13, wherein the reticulated matrix post said gelation contains ruptured cell membranes and cell windows for substantially continuous passage of combustion gases during reticulation.

15. The process of claim 9, wherein the reticulated matrix comprises a reticulated, resiliently-compressible, elastomeric matrix that promotes tissue ingrowth and comprises a continuous network of intercommunicating and inter-connected solid void space, wherein said void space comprises a plurality of interconnected cells and pores that are fully accessible.

16. The process of claim 9, wherein hydrolytic degradation rates of the reticulated matrix are controllable through multiple different mechanisms.

17. The process of claim 9, wherein the foaming comprises reacting (a) a soft segment comprising a polycaprolactone copolymer polyol and (b) a hard segment comprising an isocyanate having cross-linking and optionally having a chain extender.