Bioabsorbable, biobeneficial polyurethanes for use in medical devices

• US 7,795,467 B1
• Filed: 04/26/2005
• Issued: 09/14/2010
• Est. Priority Date: 04/26/2005
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Claude, Charles, Astafieva, Irina, Pacetti, Stephen Dirk
• Primary Examiner(s): OLSON, ERIC
• Application Number:
  US11/115,699
• Time in Patent Office: 1,967 Days
• Field of Search: None
• US Class Current: 560/336
• CPC Class Codes: C07C 275/16 being further substituted by carboxyl groups

Abstract

Bioabsorbable, polyurethane-based stent coatings that comprise non-fouling coatings with polyethylene glycol and hyaluronic acid are disclosed. In addition to these coatings, medical devices comprising these coatings and methods of applying the coatings are disclosed.

Claims

1. A composition comprising:

an A-moiety derived from a diisocyanate;

a B-moiety derived from a chain extender; and

a C-moiety derived from a biobeneficial moiety selected from the group consisting of poly(ethylene glycol), poly(propylene glycol), polyethylene oxide, PEO-PPO surfactants, PLURONIC surfactants, poly(tetramethylene glycol), amino-terminated PEG, hydroxy functional poly(vinyl pyrrolidone), dextran, dextrin, sulfonated dextran, dermatan sulfate, Silk-elastin protein block-copolymers, sodium hyaluronate, hyaluronic acid, poly(2-hydroxyethyl methacrylate), dihydroxy poly(styrene sulfonate), poly(3-hydroxypropyl methacrylate), poly(3-hydroxypropyl methacrylamide), poly(alkoxy methacrylates), poly(alkoxy acrylates), polyarginine peptides (PAP), phosphoryl choline, heparin, chondroitin sulfate, glycosaminoglycans, chitosan, polyethylene oxide, or any combination of these;

wherein;

the composition comprises one of the following formulas;

2. The composition of claim 1 wherein diisocyanate(s) are selected such that at least one hydrolysis product of the diisocyanate(s) is a biocompatible diamine.

3. The composition of claim 1 wherein the diisocyanate is an aliphatic diisocyanate.

4. The composition of claim 3 wherein the diisocyanate is 1,4-diisocyanatobutane, 1,2-diisocyanatoethane, lysine ester diisocyanate, 1,5-diisocyanatopentane, or any combination of these.

5. The composition of claim 1 wherein the chain extender is biocompatible.

6. The composition of claim 1 wherein the biobeneficial moiety is connected to a hydroxyacid, a hydroxyacid composition, a hydroxyacid oligomer, an amino acid, an amino acid composition, or an amino acid oligomer.

7. The composition of claim 5 wherein the chain extender comprises an alcohol-amine, a diamine, a diol, a dithiol, or any combination of these.

8. The composition of claim 7 wherein

the diamine is selected from 1,4-butanediamine, lysine ester, 1,2-ethanediamine, arginine ethyl ester, 1,5-pentanediamine, or any combination of these;

or

the diol is selected from 1,3-propanediol, 1,2-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,10-decanediol, cyclohexanedimethanol, and poly(caprolactone)diol, 1,5-pentanediol, 1,4-cyclohexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,12-dodecanediol, poly(caprolactone) diol, or any combination of these.

9. The composition of claim 1 wherein:

the A-moiety is derived from a compound with a formula

10. The composition of claim 9 wherein Q1 and Q2 independently represent 1-20 carbon atom moieties.

11. The composition of claim 9 wherein W1 and W2 independently represent —

OH or —

NH₂.

12. The composition of claim 9 wherein A1 and A2 independently represent bioabsorbable hydroxy-acid radicals, a metabolic precursor to bioabsorbable hydroxy-acid radicals, bioabsorbable amino acid radicals, or a metabolic precursor to bioabsorbable amino acid radicals.

13. The composition of claim 10 wherein

the hydroxyacid is selected from 2-hydroxyacids, 3-hydroxy acids, 4-hydroxy acids, or ε

-hydroxy-caproic acid, oligomers of the above, or any combination of these;

or

the amino acid is glycine, valine, leucine, isoleucine, proline, phenylalanine, oligomers of the above, or any combination of these.

14. The composition of claim 9 wherein the biobeneficial moiety is poly(ethylene glycol), poly(propylene glycol), polyethylene oxide, PEO-PPO surfactants, PLURONIC surfactants, poly(tetramethylene glycol), amino-terminated PEG, hydroxy functional poly(vinyl pyrrolidone), dextran, dextrin, sulfonated dextran, dermatan sulfate, Silk-elastin protein block-copolymers, sodium hyaluronate, hyaluronic acid, poly(2-hydroxyethyl methacrylate), dihydroxy poly(styrene sulfonate), poly(3-hydroxypropyl methacrylate), poly(3-hydroxypropyl methacrylamide), poly(alkoxy methacrylates), poly(alkoxy acrylates), polyarginine peptides (PAP), phosphoryl choline, heparin, chondroitin sulfate, glycosaminoglycans, chitosan, polyethylene oxide, or any combination of these.

15. The composition of claim 1 of the following formula:

17. A medical device comprising at least one type-one polymer, wherein type-one polymers are the compositions of claim 1.

18. A medical device comprising at least one type-one polymer, wherein type-one polymers are the compositions of claim 9.

19. The medical device of claim 17 wherein the type-one polymer is coated onto the surface of the device to form a layer of polymer.

20. The medical device of claim 17 further comprising another type-one polymer, wherein the type-one polymer is disposed on the surface of the device to form a polymer layer and another type-one polymer is disposed on the polymer layer.

21. The medical device of claim 17 further comprising a type-two polymer, wherein type-two polymers are biocompatible and are selected from polycaprolactone, poly(D,L-lactide), poly(L-lactide), poly(D,L-lactide-co-L-lactide), poly(glycolide), poly(D,L-lactide-co-glycolide), poly(dioxanone), poly(4-hydroxybutyrate), poly(3-hydroxybutyrate), poly(3-hydroxy valerate), poly(hydroxybutyrate-co-hydroxyvalerate), poly(tyrosine derive carbonates), poly(tyrosine arylates), poly(imino carbonates), poly(trimethylene carbonate), poly(anhydrides), poly(orthoesters), poly(ester amides) or their mixtures.

22. The medical device of claim 21 comprising at least one inner layer and one outer layer wherein

the inner layer is a type-two polymer and the outer layer is a type-one polymer;

or

the inner layer is a type-one polymer and the outer layer is a type-two polymer.

23. The medical device of claim 17 further comprising at least one therapeutic agent.

24. The medical device of claim 23 wherein the therapeutic agent is selected from proteins, peptides, antiproliferatives, antineoplastics, antiinflammatories, antiplateletes, anticoagulants, antifibrins, antithrombins, antimitotics, antibiotics, antioxidants, or their mixtures.

25. A method of preparing the composition of claim 1 comprising:

reacting an amount of hydroxy-acid- or amino-acid-modified biobeneficial composition with an amount of diisocyanate to yield an intermediate; and

reacting the intermediate with a chain extender.

26. The method of claim 25 wherein the amount of hydroxy-acid- or amino-acid-modified biobeneficial composition ranges from 0.1 mole % to 100 mole % of the amount of diisocyanate or ranges from 0.1 weight % to 100 weight % of the amount of diisocyanate.

27. The method of claim 26 wherein the amount of hydroxy-acid- or amino-acid-modified biobeneficial composition ranges from 0.33 mole % to 3 mole % of the amount of diisocyanate or ranges from 0.33 weight % to 3 weight % of the amount of diisocyanate.

28. The method of claim 25 wherein the diisocyanate is selected such that the hydrolysis product of the diisocyanate is a biocompatible diamine.

29. The method of claim 28 wherein the diisocyanate is an aliphatic diisocyanate.

30. The method of claim 25 wherein the chain extender is biocompatible.

31. The method of claim 29 wherein the diisocyanate is 1,4-diisocyanatobutane, 1,2-diisocyanatoethane, lysine ester diisocyanate, 1,5-diisocyanatopentane, or any combination of these.

32. The method of claim 30 wherein the chain extender comprises an alcohol-amine, a diamine, a diol, or any combination of these.

33. The method of claim 32 wherein the diamine or diol is 1,4-butanediamine, Lysine Ester, 1,2-ethanediamine, Arginine Ethyl Ester, 1,5-pentanediamine, 1,3-propanediol, 1,2-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,10-decanediol, cyclohexanedimethanol, and poly(caprolactone)diol, 1,5-pentanediol, 1,4-cyclohexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,12-dodecanediol, caprolactone diol, or any combination of these.

34. The method of claim 25 wherein the biobeneficial moiety is poly(ethylene glycol), poly(propylene glycol), polyethylene oxide, PEO-PPO surfactants, PLURONIC surfactants, poly(tetramethylene glycol), amino-terminated PEG, hydroxy functional poly(vinyl pyrrolidone), dextran, dextrin, sulfonated dextran, dermatan sulfate, Silk-elastin protein block-copolymers, sodium hyaluronate, hyaluronic acid, poly(2-hydroxyethyl methacrylate), dihydroxy poly(styrene sulfonate), poly(3-hydroxypropyl methacrylate), poly(3-hydroxypropyl methacrylamide), poly(alkoxy methacrylates), poly(alkoxy acrylates), polyarginine peptides (PAP), phosphoryl choline, heparin, chondroitin sulfate, glycosaminoglycans, chitosan, polyethylene oxide, or any combination of these.

35. A polymer blend comprising at least two different type-one polymers,

wherein type-one polymers are the compositions of claim 1.

36. A polymer blend comprising

at least one type-one polymer, wherein type-one polymers are the compositions of claim 1;

and

the type-two polymer, wherein the type-two polymer is a biocompatible polymer different from the at least one type-one polymer.

37. The polymer blend of claim 36 wherein type-two polymers are polycaprolactone, poly(D,L-lactide), poly(L-lactide), poly(D,L-lactide-co-L-lactide), poly(glycolide), poly(D,L-lactide-co-glycolide), poly(dioxanone), poly(4-hydroxybutyrate), poly(3-hydroxybutyrate), poly(3-hydroxy valerate), poly(hydroxybutyrate-co-hydroxyvalerate), poly(tyrosine derive carbonates), poly(tyrosine arylates), poly(imino carbonates), poly(trimethylene carbonate), poly(anhydrides), poly(orthoesters), poly(ester amides) or their mixtures.

16. A composition comprising a polymer comprising:

an A-moiety derived from a diisocyanate, wherein the diisocyanate is 1,4-diisocyanatobutane, 1,2-diisocyanatoethane, lysine ester diisocyanate, 1,5-diisocyanatopentane, or any combination of these;

a B-moiety derived from a chain extender comprising an alcohol-amine, diamine, diol or any combination of these wherein the diamine or diol is 1,4-butanediamine, Lysine Ester, 1,2-ethanediamine, Arginine Ethyl Ester, 1,5-pentanediamine, 1,3-propanediol, 1,2-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,10-decanediol, cyclohexanedimethanol, and poly(caprolactone)diol, 1,5-pentanediol, 1,4-cyclohexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,12-dodecanediol, caprolactone diol, or any combination of these; and

a C-moiety derived from a biobeneficial moiety wherein at least one C-moiety is appended from an A moiety as a side chain, the C-moiety comprising;

poly(ethylene glycol), poly(propylene glycol), polyethylene oxide, PEO-PPO surfactants, PLURONIC surfactants, poly(tetramethylene glycol), amino-terminated PEG, hydroxy functional poly(vinyl pyrrolidone), dextran, dextrin, sulfonated dextran, dermatan sulfate, Silk-elastin protein block-copolymers, sodium hyaluronate, hyaluronic acid, poly(2-hydroxyethyl methacrylate), dihydroxy poly(styrene sulfonate), poly(3-hydroxypropyl methacrylate), poly(3-hydroxypropyl methacrylamide), poly(alkoxy methacrylates), poly(alkoxy acrylates), polyarginine peptides (PAP), phosphoryl choline, heparin, chondroitin sulfate, glycosaminoglycans, chitosan, polyethylene oxide, or any combination of these, and

a hydroxyacid selected from 2-hydroxyacids, 3-hydroxy acids, 4-hydroxy acids, or ε

-hydroxy-caproic acid, oligomers of the above, or any combination of these;

or the amino acid is glycine, valine, leucine, isoleucine, proline, phenylalanine, oligomers of the above, or any combination of these,

wherein the biobeneficial moiety has a maximum molecular weight of 40,000±

4,000 Daltons.