Semi-interpenetrating polymer networks

• US 5,837,752 A
• Filed: 07/17/1997
• Issued: 11/17/1998
• Est. Priority Date: 07/17/1997
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Tarcha, Peter J., Langer, Robert S., Shastri, Venkatram R.
• Primary Examiner(s): BUTTNER, DAVID J
• Application Number:
  US08/895,762
• Time in Patent Office: 488 Days
• Field of Search: 523/115, 523/116, 525/59, 525/404, 525/411, 525/412, 525/445, 525/450, 525/903, 522/142, 424/423, 424/426, 606/76, 606/77, 623/16
• US Class Current: 523/116
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30583 filled with hardenable fluid, e.g. curable in-situ
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0085 hardenable in situ, e.g. epoxy resins
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: C08F 283/00 Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
• CPC Class Codes: Y10S 525/903 Interpenetrating network
• CPC Class Codes: Y10S 623/923 Bone

Abstract

Compositions for bone repair have been developed based on linear hydrophobic degradable polymers and monomers or macromers, at least one of which includes an anhydride linkage. The monomers and/or macromers crosslink each other but not to the linear polymer to form semi-interpenetrating networks. The compositions can include various excipients, therapeutic and/or diagnostic agents. The compositions can be polymerized in the presence of dissolvable particles such as inorganic salts and proteinaceous materials to provide a porous polymer network. The compositions can be injected into a patient and polymerized in situ or can be polymerized ex vivo and implanted. When polymerized ex vivo, the composition can be shaped into various articles, such as pins, screws, and hollow tubes, which can be used to repair broken bones.

Claims

1. A composition which forms a semi-interpenetrating polymer network following exposure to active species comprising

a) a linear polymer selected from the group consisting of linear, hydrophobic biodegradable polymers and linear non-degradable hydrophilic polymers;

and

b) at least one monomer or macromer containing at least one free radical polymerizable group, wherein at least one of the monomers or macromers includes an anhydride linkage and a polymerizable group selected from the group consisting of acrylate or methacrylate.

2. The composition of claim 1 in a form suitable for repair or replacement of bone.

3. The composition of claim 1, wherein the biodegradable polymer is formed from one or more monomeric units selected from the group consisting of polyanhydrides, polyorthoesters, polyhydroxy acids, polydioxanones, polycarbonates, and polyaminocarbonates.

4. The composition of claim 1, wherein the biodegradable polymer is formed from one or more monomeric units selected from the group consisting of polyhydroxy acids and polyanhydrides.

5. The composition of claim 1, wherein the monomer or macromer is a methacrylate.

6. The composition of claim 1, wherein the monomer or macromer is polymerized, whereby the composition is in the form of a semi-interpenetrating network.

7. The composition of claim 1, further comprising an excipient selected from the group consisting of hydroxyapatite, plaster of paris, calcium carbonate, tricalcium phosphate, polyphosphates, polyphosphonates and polyphosphites.

8. The composition of claim 1 wherein the covalently crosslinkable monomer or macromer is present in a weight percentage of between 30 and 70 percent by weight.

9. The composition of claim 1 wherein the linear polymer is present in a weight percentage of between 10 and 90 percent by weight.

10. The composition of claim 1, further comprising one or more diagnostic or therapeutic agents.

11. The composition of claim 10, wherein the diagnostic or therapeutic agents are incorporated into a microparticle.

12. The composition of claim 1, further comprising one or more porosity forming agents selected from the group consisting of inorganic salts and proteinaceous materials.

13. A method for repairing or regenerating bone or creating solid prosthetic articles in situ comprising:

a) injecting into a patient a composition comprising

i) a linear polymer selected from the group consisting of linear hydrophobic biodegradable polymers and linear non-degradable hydrophilic polymers;

ii) at least one monomer or macromer containing at least one free radical polymerizable group, wherein at least one of the monomers or macromers includes an anhydride linkage;

b) forming a semi-interpenetrating network upon exposure to active species.

14. The method of claim 13 wherein the polymer is formed from one or more monomeric units selected from the group consisting of polyanhydrides, polyorthoesters, polyhydroxy acids, polydioxanones, polycarbonates, and polyaminocarbonates.

15. The method of claim 13 wherein the polymer is formed from one or more monomeric units selected from the group consisting of polyhydroxy acids and polyanhydrides.

16. The method of claim 13 wherein the monomer or macromer is a (meth)acrylate.

17. The method of claim 13 wherein the composition further comprises an excipient selected from the group consisting of hydroxyapatite, plaster of paris, calcium carbonate, tricalcium phosphate, polyphosphates, polyphosphonates and polyphosphites.

18. The method of claim 13 wherein the covalently crosslinkable monomer or macromer is present in a weight percentage of between 30 and 70 percent by weight.

19. The method of claim 13 wherein the linear polymer is present in a weight percentage of between 10 and 90 percent by weight.

20. The method of claim 13 wherein the composition further comprises one or more diagnostic or therapeutic agents.

21. The method of claim 20 wherein the diagnostic or therapeutic agents are incorporated into a microparticle.

22. The method of claim 13 wherein the composition further comprises one or more porosity forming agents selected from the group consisting inorganic salts and proteinaceous materials.

23. A method for preparing solid articles for use in repairing or regenerating bone comprising

a) casting or injecting into a suitable mold a composition comprising

i) a linear polymer selected from the group consisting of linear hydrophobic biodegradable polymers and linear non-degradable hydrophilic polymers;

ii) at least one monomer or macromer containing at least one free radical polymerizable group, wherein at least one of the monomers or macromers includes an anhydride linkage;

b) forming a semi-interpenetrating network upon exposure to active species.

24. The method of claim 23 wherein the polymer is formed from one or more monomeric units selected from the group consisting of polyanhydrides, polyorthoesters, polyhydroxy acids, polydioxanones, polycarbonates, and polyaminocarbonates.

25. The method of claim 23 wherein the polymer is formed from one or more monomeric units selected from the group consisting of polyhydroxy acids and polyanhydrides.

26. The method of claim 23 wherein the monomer or macromer is a (meth)acrylate.

27. The method of claim 23 wherein the composition further comprises an excipient selected from the group consisting of hydroxyapatite, plaster of paris, calcium carbonate, tricalcium phosphate, polyphosphates, polyphosphonates and polyphosphites.

28. The method of claim 23 wherein the covalently crosslinkable monomer or macromer is present in a weight percentage of between 30 and 70 percent by weight.

29. The method of claim 23 wherein the linear polymer is present in a weight percentage of between 10 and 90 percent by weight.

30. The method of claim 23 wherein the composition further comprises one or more diagnostic or therapeutic agents.

31. The method of claim 30 wherein the diagnostic or therapeutic agents are incorporated into a microparticle.

32. The method of claim 23 wherein the composition further comprises one or more porosity forming agents selected from the group consisting inorganic salts and proteinaceous materials.