Biocompatible, biodegradable polyurethane materials with controlled hydrophobic to hydrophilic ratio

Patent metadata

Field	Value
Publication number	US-9511173-B2
Application number	US-201514706576-A
Country	US
Kind code	B2
Filing date	May 7, 2015
Priority date	Jul 26, 2004
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

The biocompatible, biodegradable materials in the solid and/or liquid form are based on segmented linear polyurethanes and/or segmented crosslinked polyurethanes based on A) one or more biocompatible polyols susceptible to hydrolytic and/or enzymatic degradation having a molecular weight of 100 to 20,000 dalton and a number of active hydroxyl groups per molecule (functionality) of at least two or higher: B) one or more diisocyanates and/or triisocyanates; and C) one or more low molecular weight chain extenders having a molecular weight of 18 to 1000 dalton and the functionality of at least two or higher.

First claim

The invention claimed is:

1. A biocompatible, biodegradable material comprising creatine and segmented linear polyurethane-acrylates and/or segmented crosslinked polyurethane-acrylates, wherein said segmented linear polyurethane-acrylates and/or segmented crosslinked polyurethane-acrylates are prepared from:
A) at least two biocompatible polyols, wherein said polyols are:
(i) susceptible to hydrolytic and/or enzymatic degradation and
(ii) have a molecular weight of 100 to 20,000 daltons and a number of active hydroxyl groups per molecule of at least two or higher;

B) one or more aliphatic diisocyanates and/or aliphatic triisocyanates;
C) one or more low molecular weight chain extenders having
(i) a molecular weight of 18 to 1,000 daltons and
(ii) the functionality of at least two or higher; and

D) one or more hydroxyacrylates,
wherein said biocompatible, biodegradable material is in the form of a micro- and/or macroporous membranous and/or spongy structure or body.

2. The biocompatible, biodegradable material of claim 1 , wherein at least two of said polyols have a different hydrophilicity.

3. The biocompatible, biodegradable material of claim 1 , wherein all of said polyols are hydrophilic.

4. The biocompatible, biodegradable material of claim 1 , wherein all of said polyols are hydrophobic.

5. The biocompatible, biodegradable material of claim 1 , wherein at least one of said polyols has amphiphilic qualities.

6. The biocompatible, biodegradable material of claim 1 , wherein said polyols are selected from the group consisting of poly(aminobutyrate) diols, poly(ε-caprolactone) diols, poly(ethylene oxide) diols, amphiphilic poly(ethylene oxide-propylene oxide-ethylene oxide) diols, poly(oxalate diols), aminoalcohols soy diols, cyclodextrins, aminosugars, and sugar alcohols.

7. The biocompatible, biodegradable material of claim 1 , wherein said polyols have a molecular weight in the range of 200 to 10,000 daltons.

8. The biocompatible, biodegradable material of claim 1 , wherein the functionality of said chain extenders relates to the functional group —OH, —NH2, —SH, or —COOH.

9. The biocompatible, biodegradable material of claim 1 , wherein said chain extenders have a molecular weight in the range 18 to 500 daltons.

10. The biocompatible, biodegradable material of claim 1 , wherein said chain extenders have biologically and/or pharmacologically active properties.

11. The biocompatible, biodegradable material of claim 1 , wherein the creatine is incorporated chemically in the material.

12. The biocompatible, biodegradable material of claim 1 , wherein the creatine is incorporated physically in the material.

13. The biocompatible, biodegradable material of claim 1 , wherein the creatine is present in an amount of 0.005% to 20% of the total weight of the material.

14. The biocompatible, biodegradable material of claim 1 , further comprising one or more biologically and/or pharmacologically active components selected from the group consisting of oligosaccharides (chitosan-oligosaccharides with the D-glucosamines bonded by β-1,4 bonding, maltooligosaccharides, chitooligosaccharides), sugar alcohols, cyclodextrins, modified soy, various aminoalcohols (L-alaninol, L-asparginol, L-glutaminol, L-glycinol, L-lysinol, L-prolinol, L-tryptophanol, pyrrolidinemethanol, isoleucinol), various aminoacids, glycyl-L-glutamine, glycyl-L: tyrosine, L-glutathione, glycylglycine, L-malic acid, 2-mercaptoethyl ether, citric acid, ascorbic acid, lecithin, and polyaspartates.

15. The biocompatible, biodegradable material of claim 1 , wherein said aliphatic diisocyanates are selected from the group consisting of 1,6-hexamethylene diisocyanate, 1,4-diisocyanato butane, L-lysine diisocyanate, isophorone diisocyanate, 1,4-diisocyanato 2-methyl butane, 2,3-diisocyanato 2,3-dimethyl butane, 1,4-di(1propoxy-3-diisocyanate, 1,4-diisocyanato 2-butene, 1,10-diisocyanato decane, ethylene diisocyanate, 2,5 bis(2-isocyanato ethyl) furan, 1,6-diisocyanato 2,5-diethyl hexane, 1,6-diisocyanato 3-methoxy hexane, 1,5 diisocyanato pentane, 1,12-dodecamethylene diisocyanate, 2 methyl-2,4 diisocyanato pentane, 2,2 dimethyl-1,5 diisocyanato pentane, ethyl phosphonyl diisocyanate, 2,2,4-trimethyl-1, 6-hexamethylene diisocyanate, 4,4′-dicyclohexylmethane diisocyante (H 12 MDI), trans 1,4-cyclohexane diisocyanate, m-tetramethylxylylen diisocyanate, m-isopropenyldimethylbenzyl, “dimeryl” diisocyanate derived from dimerized linoleic acid, xylylene diisocyanate, and 1,1,6,6-tetrahydroperfluorohexamethylene diisocyanate.

16. The biocompatible, biodegradable material of claim 1 , wherein said chain extenders are selected from the group consisting of water, thiodiethylene diol, 2-mercaptoethyl ether, isosorbide diols, citric acid, ascorbic acid, aminobutyric acid, aminoethanol, 2-aminoethanol, 2-dibutylaminoethanol, n-alkyl-diethanolamines, n-methyl-diethanolamine, ethylene diol, diethylene diol, 1,4-butanediol, propylene diol, dipropylene diol, 1,6-hexanediol, 1,4:3,6-dianhydro-D-sorbitol, 1,4:3,6-dianhydro-D-mannitol, 1,4:3,6-dianhydro-L-iditol, glycerol, ethylene diamine, tetramethylene diamine, hexamethylene diamine, isophorone diamine, pro-panolamine, ethanolamine, glycyl-L-Glutamine, glycyl-L-tyrosine, L-Glutathione, glycylglycine, L-malic acid, and mixtures of these compounds.

17. The biocompatible, biodegradable material of claim 1 , which has a hard segment content in the range of 5% to 100% and a soft segment which forms the remaining part of the material.

18. The biocompatible, biodegradable material of claim 1 , which has amphiphilic properties.

19. The biocompatible, biodegradable material of claim 1 , having a ratio of hydrophilic polyols to hydrophobic polyols in the range of 2:1 to 2.6:1.

20. The biocompatible, biodegradable material of claim 1 , which degrades within 2 to 18 months or within 4 to 12 months.

21. The biocompatible, biodegradable material of claim 1 , which has a glass transition temperature in the range of −60° C. to +70° C.

22. The biocompatible, biodegradable material of claim 1 , which, upon degradation, degrades into nontoxic by-products.

23. The biocompatible, biodegradable material of claim 1 , which has a molecular weight in the range of 10,000 to 300,000 dalton.

24. The biocompatible, biodegradable material of claim 1 , wherein the membranous and/or spongy structure or body contains pores having a pore size in the range of 0.1 to 5,000 micrometers.

25. The biocompatible, biodegradable material of claim 1 , which is designed as a scaffold suitable for bone substitute, articular cartilage repair or soft tissue repair.

26. The biocompatible, biodegradable material of claim 1 , which is designed as an artificial periosteum.

27. The biocompatible, biodegradable material of claim 1 , which is designed as artificial skin or as a wound dressing.

28. The biocompatible, biodegradable material of claim 1 , which is designed as a cardiovascular implant, pericardial patch or a vascular prostheses.

29. The biocompatible, biodegradable material of claim 1 , which is designed as a bone graft substitute.

30. The biocompatible, biodegradable material of claim 1 , which is designed as an articular cartilage repair.

31. The biocompatible, biodegradable material of claim 1 , which is designed as a tissue engineered scaffold.

Assignees

• Depuy Synthes Products Inc

Inventors

• Gogolewski Sylwester

Classifications

• A61L26/0019 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• C08G18/3203

  Polyhydroxy compounds · CPC title

• C08G18/73

  acyclic · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title