Mixed-phase biomaterials

• US 9,669,135 B2
• Filed: 07/30/2015
• Issued: 06/06/2017
• Est. Priority Date: 07/31/2014
• Status: Active Grant

• Current Assignee: Proton Innovations, LLC
• Original Assignee: Proton Innovations, LLC
• Inventors: Bonafini, Jr., James A.
• Primary Examiner(s): Dollinger, Mike M
• Application Number:
  US14/813,814
• Publication Number:
  US 20160030641A1
• Time in Patent Office: 677 Days
• Field of Search: 525454
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 25/0017 specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
• CPC Class Codes: C08G 18/3206 aliphatic
• CPC Class Codes: C08G 18/638 characterised by the use of compounds having carbon-to-carbon double bonds other than styrene and/or olefinic nitriles
• CPC Class Codes: C08G 18/6564 with compounds of group C08G18/3203
• CPC Class Codes: C08G 18/7671 containing only one alkylene bisphenyl group
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

A method of preparing a mixed-phase thermoplastic biomaterial comprises contacting and reacting a diol and a graft pre-polymer comprising a diol and at least one covalently bonded unsaturated monomer with an organic diisocyanate compound. The reaction is conducted within an aprotic solvent and for a period of time and at a temperature sufficient to produce the mixed-phase thermoplastic biomaterial. The diol may be selected from the group consisting of siloxane diols, polyether diols, polyester diols and polycarbonate diols while the at least one covalently bonded unsaturated monomer may be selected from the group consisting of a fluorinated monomer, a siloxane monomer, an aliphatic ester of methacrylic acid, a cyclic ester of methacrylic acid, a charged monomer, a sulfonium salt, a vinyl monomer with phenol or benzoic acid, N-vinyl pyrrolidone, an aminoglucoside, and a therapeutic agent. The mixed-phase thermoplastic biomaterial may further include an anti-microbial, a therapeutic agent or both.

Claims

1. A method of preparing a polyurethane-based thermoplastic biomaterial which comprises contacting and reacting:

a) a diol that is selected from the group consisting of siloxane diols, polyether diols, polyester diols and polycarbonate diols;

b) a graft pre-polymer prepared from the reaction of polyethylene glycol with at least 3-[tris(trimethylsiloxy)silyl]propyl methacrylate; and

c) an organic diisocyanate compound,

the reaction being conducted within an aprotic solvent and for a period of time and at a temperature sufficient to produce the mixed-phase thermoplastic biomaterial.

2. The method of claim 1 further including contacting and reacting an interfacial agent, the interfacial agent comprising a) a solvatable constituent which is solvatable within the aprotic solvent but not compatible with diol and b) a non-solvatable constituent which is compatible with the diol but is not solvatable within the aprotic solvent.

3. The method of claim 1 wherein the thermoplastic biomaterial includes an anti-microbial, a therapeutic agent or both.

4. The method of claim 1 wherein the thermoplastic biomaterial includes at least one covalently bonded amino acid.

5. The method of claim 1 wherein the thermoplastic biomaterial exhibits multiple phase change transitions over the temperature range of about 20°

C. and about 120°

C.

6. The method of claim 5 wherein at least two of the multiple phase change transitions occurs in the temperature range of about 20°

C. and about 70°

C.

7. The method of claim 1 wherein the graft pre-polymer also contains a covalently bonded unsaturated monomer and the at least one covalently bonded unsaturated monomer is selected from the group consisting of a fluorinated monomer, a siloxane monomer, an aliphatic ester of methacrylic acid, a cyclic ester of methacrylic acid, a charged monomer, a sulfonium salt, a vinyl monomer with phenol or benzoic acid, N-vinyl pyrrolidone, an aminoglucoside, a zwitterionic monomer such as but not limited to an amino acid, phosphorycholine and the like, and a therapeutic agent.

8. A polyurethane-based thermoplastic biomaterial comprising the reaction product of:

a) a diol that is selected from the group consisting of siloxane diols, polyether diols, polyester diols and polycarbonate diols;

b) a graft pre-polymer prepared from the reaction of polyethylene glycol with at least 3-[tris(trimethylsiloxy)silyl]propyl methacrylate;

c) an organic diisocyanate compound.

9. The polyurethane-based thermoplastic biomaterial of claim 8 wherein the biomaterial is produced through a reaction being conducted within an aprotic solvent.

10. The polyurethane-based thermoplastic biomaterial of claim 9 wherein the reaction proceeds for a period of time and at a temperature sufficient to produce the mixed-phase thermoplastic biomaterial.

11. The polyurethane-based thermoplastic biomaterial of claim 8 further comprising:

d) an interfacial agent comprising;

i) a solvatable constituent which is solvatable within an aprotic solvent but not compatible with the diol and

ii) a non-solvatable constituent which is compatible with the diol but is not solvatable within the aprotic solvent.

12. The polyurethane-based thermoplastic biomaterial of claim 8 further comprising:

d) an anti-microbial, a therapeutic agent or both.

13. The polyurethane-based thermoplastic biomaterial of claim 8 wherein the mixed-phase thermoplastic biomaterial includes at least one covalently bonded amino acid.

14. The polyurethane-based thermoplastic biomaterial of claim 8 wherein the thermoplastic biomaterial exhibits multiple phase change transitions over the temperature range of about 20°

C. and about 120°

C.

15. The polyurethane-based thermoplastic biomaterial of claim 14 wherein at least two of the multiple phase change transitions occur in the temperature range of about 20°

C. to about 70°

C.

16. The polyurethane-based thermoplastic biomaterial of claim 8 wherein the graft pre-polymer also contains a covalently bonded unsaturated monomer and the at least one covalently bonded unsaturated monomer is selected from the group consisting of a fluorinated monomer, a siloxane monomer, an aliphatic ester of methacrylic acid, a cyclic ester of methacrylic acid, a charged monomer, a sulfonium salt, a vinyl monomer with phenol or benzoic acid, N-vinyl pyrrolidone, an aminoglucoside, a zwitterionic monomer, and a therapeutic agent.