Biocompatible polyurethanes modified with lower alkyl sulfonate and lower alkyl carboxylate

• US 4,880,883 A
• Filed: 06/03/1987
• Issued: 11/14/1989
• Est. Priority Date: 06/03/1987
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Cooper, Stuart L., Grasel, Timothy G.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Daley, Dennis R.
• Application Number:
  US07/057,546
• Time in Patent Office: 895 Days
• Field of Search: 528/71, 528/49, 525/454
• US Class Current: 525/454
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08G 18/0819 containing anionic or anionogenic groups
• CPC Class Codes: C08G 18/83 Chemically modified polymers
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

Modified-polyurethane block copolymers and devices formed therefrom demonstrate excellent biocompatibility and improved physical and mechanical properties. In a preferred embodiment, from about 5 to about 25 percent of urethane hydrogen atoms are replaced with propyl sulfonate and propyl carboxylate groups to provide the modified copolymer.

Claims

1. A biocompatible, substantially solid polyurethane composition comprising a polyether-polyurethane copolymer based on a mole ratio of about 1.5/0.5/1.0 to about 10/9/1 of (a) an organic diisocyanate, (b) a C₂ -C₁₄ alkyl or aryl diol or diamine or hydroxy-functional amine and (c) a polyol having a number average molecular weight from about 500 to about 3000, respectively, the copolymer being modified wherein about 5 to about 25 percent of the urethane hydrogen atoms of the copolymer are replaced with a combination of lower alkyl (C₁ -C₆) sulfonate groups and lower alkyl (C₁ -C₆) carboxylate groups.

2. The polyurethane composition of claim 1 wherein said organic diisocyanate is selected from the group consisting of 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, methylene bis(p-phenyl isocyanate), 1,5-naphthalene diisocyanate, methylene bis(p-cyclohexyl isocyanate), 1,6-hexane diisocyanate, isophorone diisocyanate and cyclohexyl diisocyanate.

3. The polyurethane composition of claim 1 wherein said diol or diamine is selected from the group consisting of 1,4-butanediol, ethylene diamine, 4,4'"'"'-methylene bis(2-chloroaniline), ethylene glycol and hexanediol.

4. The polyurethane composition of claim 1 wherein the hydroxy-functional amine is represented by the formula (HOR)₂ NR₁ SO₃ H wherein each R and R₁ are independently selected from lower alkyl (C₁ -C₆) groups.

5. The polyurethane composition of claim 1 wherein said polyol is selected from the group consisting of polyethylene oxide, polypropylene oxide, polytetramethylene oxide, polyisobutylene, 1,4-polybutadiene, polyethylene adipate, polytetramethylene adipate, polycaprolactone and polydimethylsiloxane.

6. The polyurethane composition of claim 1 wherein the number average molecular weight of the polyol is from about 500 to about 2000.

7. The polyurethane composition of claim 1 wherein the number average molecular weight of the polyol is about 1000.

8. The polyurethane composition of claim 1 wherein the mole ratio of organic diisocyanate, C₂ -C₁₄ alkyl or aryl diol or diamine or hydroxy-functional amine and polyol is about 3/2/1.

9. The polyurethane composition of claim 1 wherein about 10 to about 15 percent of the urethane hydrogen atoms of the copolymer are replaced with lower alkyl (C₁ -C₆) sulfonate groups and lower alkyl (C₁ -C₆) carboxylate groups.

10. The polyurethane composition of claim 1 including an equimolar ratio of isocyanate to hydroxyl and amine functional groups.

11. A biocompatible substantially solid poly(tetramethylene oxide)-based polyurethane composition comprising a polyether-polyurethane copolymer based on a mole ratio of about 1.5/1.0/1.0 to about 10/9/1 of an organic diisocyanate, a C₂ -C₁₄ alkyl or aryl diol or diamine and polytetramethylene oxide having a number average molecular weight of from about 500 to about 3000, respectively, the copolymer being modified wherein about 5 to about 25 percent of the urethane hydrogen atoms of the copolymer are replaced with a combination of propyl sulfonate groups and propyl carboxylate groups.

12. The poly(tetramethylene oxide)-based polyurethane composition of claim 11 wherein said organic diisocyanate is selected from the group consisting of 2,4-toluene diisocyanate, 2,6-toluene dissocyanate, methylene bis(p-phenyl isocyanate), 1,5-naphthalene diisocyanate, methylene bis(p-cyclohexylisocyanate), 1,6-hexane diisocyanate, isophorone diisocyanate and cyclohexyl diisocyanate.

13. The poly(tetramethylene oxide )-based polyurethane composition of claim 11 wherein said diol or diamine is selected from the group consisting of 1,4-butanediol, ethylene diamine, 4,4'"'"'-methylene bis(2-chloroaniline), ethylene glycol and hexanediol.

14. The poly(tetramethylene oxide)-based polyurethane composition of claim 11 wherein said polytetramethylene oxide has a number average molecular weight of about 1000.

15. The poly(tetramethylene oxide)-based polyurethane composition of claim 11 wherein the mole ratio of organic diisocyanate, C₂ -C₁₄, alkyl or aryl diol or diamine and polytetramethylene oxide is about 3/2/1.

16. A biocompatible poly(tetramethylene oxide)-based polyurethane composition comprising a polyetherpolyurethane copolymer based on a 3/2/1 mole ratio of about 1.5/0.5/1.0 to about 10/9/1 of methylene bis(p-phenyl isocyanate), 1,4-butanediol, and polytetramethylene oxide having a number average molecular weight from about 500 to about 3000, wherein about 5 to about 25 percent of the urethane hydrogen atoms of the copolymer are replaced with a combination of propyl sulfonate groups and propyl carboxylate groups.

17. The poly(tetramethylene oxide)-based polyurethane composition of claim 16 wherein about 10 to about 15 percent of the urethane hydrogen atoms of the copolymer are replaced with a combination of propyl sulfonate groups and propyl carboxylate groups.

18. A method for the production of a modified and substantially solid polyether-polyurethane copolymer composition which is biocompatible and which provides improved physical and mechanical properties, said method comprising the steps of:

(a) providing a polyether-polyurethane copolymer based on a 3/2/1 mole ratio of an organic diisocyanate, a C₂ -C₁₄ alkyl or aryl diol or diamine and a polyol;

(b) modifying the copolymer by replacing up to about 25 percent of the urethane hydrogen atoms thereof with a combination of propyl sulfonate groups and propyl carboxylate groups in the presence of a solvent; and

(c) removing the solvent by drying the modified copolymer.

19. The method according to claim 18 wherein up to about 20 percent of said urethane hydrogen atoms are replaced by treatment with 1,3-propane sultone to provide a modified-urethane material.

20. The method according to claim 19 further including the step of treating the modified copolymer with a carboxyl-substituted C₁ -C₆ halide to provide a further modified-urethane material.

21. A method for the production of a modified and substantially solid poly(tetramethylene oxide)-based polyurethane composition comprising a polyether-polyurethane copolymer which is biocompatible and which demonstrates improved physical and mechanical properties, said method comprising the steps of:

(a) providing a polyether-polyurethane copolymer based on a 3/2/1 mole ratio of an organic diisocyanate, a C₂ -C₁₄ alkyl or aryl diol or diamine and polytetramethylene oxide having a number average molecular weight of about 1000;

(b) modifying the copolymer by replacing from about 5 to about 25 percent of the urethane hydrogen atoms thereof with a combination of propyl sulfonate groups and propyl carboxylate groups in the presence of a solvent; and

(c) removing the solvent by drying the modified copolymer.

22. The method according to claim 21 wherein said organic diisocyanate is selected from the group consisting of 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, methylene bis(phenyl isocyanate), 1,5-naphthalene diisocyanate, methylene bis(p-cyclohexyl isocyanate), 1,6-hexane diisocyanate, isophorone diisocyanate and cyclohexyl diisocyanate.

23. The method according to claim 21 wherein said diol or diamine is selected from the group consisting of 1,4-butanediol, ethylene diamine, 4,4'"'"'-methylene bis(2-chloroaniline), ethylene glycol and hexanediol.

24. The method according to claim 21 wherein up to about 20 percent of said urethane hydrogen atoms are replaced by treatment with 1,3-propane sultone to provide a modified-urethane material.

25. The method according to claim 24 further including the step of treatment the modified copolymer with a carboxy-substituted C₁ -C₆ alkyl halide to provide a further modified-urethane material.