Bioresorbable thermoset polyester/urethane elastomers

• US 9,309,347 B2
• Filed: 10/05/2011
• Issued: 04/12/2016
• Est. Priority Date: 05/20/2009
• Status: Active Grant

• Current Assignee: Lyra Therapeutics, Inc.
• Original Assignee: Biomedical Companies
• Inventors: Concagh, Danny, Cheng You, Chang, Zugates, Greg
• Primary Examiner(s): Jones, Jr., Robert
• Application Number:
  US13/253,720
• Publication Number:
  US 20120142884A1
• Time in Patent Office: 1,651 Days
• Field of Search: 525/415, 525/440.01, 525/440.04, 525/440.13, 525/440.15, 525/410, 525/411, 525/450, 525/454
• US Class Current: 1/1
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08G 18/4266 prepared from hydroxycarboxylic acids and/or lactones
• CPC Class Codes: C08G 18/4269 Lactones
• CPC Class Codes: C08G 18/4277 Caprolactone and/or substituted caprolactone
• CPC Class Codes: C08G 18/428 Lactides
• CPC Class Codes: C08G 18/72 Polyisocyanates or polyisothiocyanates
• CPC Class Codes: C08G 18/73 acyclic
• CPC Class Codes: C08G 18/771 oxygen
• CPC Class Codes: C08G 63/08 Lactones or lactides
• CPC Class Codes: C08G 63/912 derived from hydroxycarboxylic acids
• 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

Bioresorbable thermoset elastomers and methods of making the same are disclosed. In certain embodiments, the thermoset elastomers include soft segments comprising branched polyesters, and hard segments including urethane and/or urea. The thermoset elastomers are made in certain embodiments by curing a branched prepolymer with a cross-linking agent. In certain embodiments, the mechanical properties of the thermoset elastomers are tailored by selecting the average molecular weight of the prepolymer, or by tuning the ratio of prepolymer to the cross-linking agent during curing, or by selecting a cross-linking agent with specific chemical characteristics.

Claims

1. A polymer prepared by the process comprising the steps of:

providing a branched polyester having at least three branches and having a glass transition temperature less than about 25°

Centigrade, wherein the polyester has an average molecular weight (Mn) of at least 20,000 g/mol; and

at least partially crosslinking said polyester with a symmetrical isocyanate cross linker,

wherein said polymer is an elastomer.

2. The polymer of claim 1, wherein the polyester is Poly(lactide-co-ε

-caprolactone).

3. The polymer of claim 2, wherein the isocyanate crosslinker is hexamethylene diisocyanate.

4. The polymer of claim 1, wherein the polyester is Poly(glycolide-co-ε

-caprolactone).

5. The polymer of claim 4, wherein the isocyanate crosslinker is hexamethylene diisocyanate.

6. The polymer of claim 1, wherein the polyester is provided in a ratio of between 8:

1 and 20;

1 wt/wt relative to the isocyanate crosslinker during the crosslinking step.

7. The polymer of claim 1, wherein the isocyanate crosslinker is present in a ratio of between approximately 1:

1 and 120;

1 mol/mol relative to the polyester during the cross-linking step.

8. The polymer of claim 1, wherein the polyester has four branches.

9. The polymer of claim 1, wherein the isocyanate crosslinker comprises two or more isocyanate groups of equal reactivity.

10. The polymer of claim 1, wherein the isocyanate crosslinker is chosen for its lack of steric hindrance.

22. The polymer of claim 1, wherein said polymer is a thermoset elastomer.

23. The polymer of claim 22, wherein said polymer is a bioresorbable thermoset elastomer.

24. The polymer of claim 1, wherein the polymer exhibits an elongation at break that ranges from 280% to 940%.

25. The polymer of claim 24, wherein the polyester has an average molecular weight (Mn) of at least 30,000 g/mol.

26. The polymer of claim 1, wherein the polyester has an average molecular weight (Mn) of at least 30,000 g/mol.

27. The polymer of claim 1, wherein the polyester has an average molecular weight (Mn) ranging from 30,000 g/mol to 100,000 g/mol.

28. The polymer of claim 26, wherein the polyester is Poly(lactide-co-ε

-caprolactone) or Poly(glycolide-co-ε

-caprolactone).

11. A polymer prepared by the process comprising the steps of:

providing a branched prepolymer with an average molecular weight of between 33 kDa and 65 kDa, the prepolymer having at least three branches and having a glass transition temperature less than about 25°

Centigrade; and

curing said polymer with an isocyanate crosslinker.

12. The polymer of claim 11, wherein the prepolymer is a polyester.

13. The polymer of claim 11, wherein the isocyanate crosslinker is symmetrical.

14. The polymer of claim 11, wherein the prepolymer is Poly(lactide-co-ε

-caprolactone.

15. The polymer of claim 14, wherein the isocyanate crosslinker is hexamethylene diisocyanate.

16. The polymer of claim 11, wherein the prepolymer is Poly(glycolide-co-ε

-caprolactone.

17. The polymer of claim 16, wherein the isocyanate crosslinker is hexamethylene diisocyanate.

18. The polymer of claim 11, wherein the prepolymer is provided in a ratio of between 8:

1 and 20;

1 wt/wt relative to the isocyanate crosslinker during the curing step.

19. The polymer of claim 11, wherein the curing step takes place at 100°

C.

20. The polymer of claim 11, wherein the curing step is performed over 16 hours.

21. The polymer of claim 11, wherein the method further comprises the steps of:

dissolving the prepolymer and the isocyanate crosslinker in a solvent; and

removing the solvent by evaporation.