Biocompatible phase invertable proteinaceous compositions and methods for making and using the same
View Patent ↗Biocompatible phase invertable proteinaceous compositions and methods for making and using the same are provided. The subject phase invertable compositions are prepared by combining a proteinaceous substrate and a cross-linker. The proteinaceous substrate includes one or more proteins and an adhesion modifier, and may also include one or more of: a plasticizer, a carbohydrate, or other modification agent. In certain embodiments, the cross-linker is a heat-treated dialdehyde, e.g., heat-treated glutaraldehyde. Also provided are kits for use in preparing the subject compositions. The subject compositions, kits and systems find use in a variety of different applications.
1. A method of producing a phase invertable composition, said method comprising:
combining:
(a) a substrate comprising a proteinaceous material; and
(b) a heat-stabilized aldehyde crosslinking agent that has been produced by maintaining an initial aldehyde crosslinking composition at an elevated temperature that ranges from about 45 to about 55° C. for a period of time that ranges from about 1 to about 20 days;
to produce said phase invertable composition.
2. The method according to claim 1 , wherein said proteinaceous material comprises one or more of: albumin, elastin, fibrin and soluble and insoluble forms of collagen and combinations thereof.
3. The method according to claim 1 , wherein said substrate further comprises an adhesion modifier.
4. The method according to claim 3 , wherein said adhesion modifier is chosen from polyethyleneimine, gelatin and carboxymethylcellulose.
5. The method according to claim 1 , wherein said substrate further comprises a plasticizer.
6. The method according to claim 5 , wherein the plasticizer is chosen from polyethylene glycol, glycerin, a fatty acid, butylhydroxytoluene, and combinations thereof.
7. The method according to claim 1 , wherein said substrate further comprises a carbohydrate.
8. The method according to claim 1 , wherein said substrate further comprises a filler.
9. The method according to claim 1 , wherein said substrate further comprises a polyblend of one or more modifying polymers.
10. The method according to claim 1 , wherein said substrate further comprises a biologically active agent.
11. The method according to claim 1 , wherein said substrate further comprises a foaming agent.
12. The method according to claim 1 , wherein said heat-stabilized aldehyde crosslinking agent comprises heat-stabilized glutaraldehyde.
13. A method of placing a biocompatible composition to a site of a subject, said method comprising:
(a) preparing a phase invertable composition by combining:
(i) a substrate comprising a proteinaceous material; and
(ii) a heat-stabilized aldehyde crosslinking agent that has been produced by maintaining an initial dialdehyde crosslinking composition at an elevated temperature that ranges from about 45 to about 55° C. for a period of time that ranges from about 1 to about 20 days;
to produce said phase invertable composition; and
(b) introducing said phase invertable composition to said site of said subject.
14. The method according to claim 13 , wherein said phase invertable composition is prepared at a site external to said subject.
15. The method according to claim 13 , wherein said phase invertable composition is prepared at said site.
16. A kit for producing a phase invertable composition, said kit comprising:
(a) a substrate comprising a proteinaceous material;
(b) a heat-stabilized aldehyde crosslinking agent that has been produced by maintaining an initial dialdehyde crosslinking composition at an elevated temperature that ranges from about 45 to about 55° C. for a period of time that ranges from about 1 to about 20 days.
17. The kit according to claim 16 , wherein said kit further comprises a phase invertable fluid delivery device.
18. The method according to claim 1 , wherein the heat stabilized aldehyde crosslinking agent comprises a heat stabilized dialdehyde.
19. A method of producing a phase invertible composition, said method comprising:
combining:
(a) a substrate comprising a proteinaceous material; and
(b) a heat-stabilized aldehyde crosslinking agent that produces pyridinium crosslinks of proteins of the proteinaceous material;
to produce said phase invertable composition.
20. The method according to claim 19 , wherein the heat stabilized aldehyde crosslinking agent comprises a heat stabilized dialdehyde.
21. The method according to claim 19 , wherein said heat-stabilized aldehyde crosslinking agent comprises heat-stabilized glutaraldehyde.