Biocompatible phase invertible proteinaceous compositions and methods for making and using the same
View Patent ↗Biocompatible phase invertible proteinaceous compositions and methods for making and using the same are provided. The subject phase invertible compositions are prepared by combining a crosslinker and a proteinaceous substrate. The proteinaceous substrate includes one or more proteins and a polyamine, where the polyamine and a proteinaceous substrate are present in synergistic viscosity enhancing amounts, and may also include one or more of: a carbohydrate, a tackifying agent, a plasticizer, or other modification agent. In certain embodiments, the crosslinker 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 invertible composition, said method comprising: combining:
(a) a liquid substrate comprising a polyamine and a proteinaceous material in a weight ratio having a synergistic viscosity enhancing effect, the weight ratio of polyamine to proteinaceous material being about 1:10 to 40, wherein the combination of the polyamine and the proteinaceous material has a viscosity which is greater than that of either the polyamine or the proteinaceous material alone; and
(b) a liquid crosslinking agent cause the polyamine and the proteinaceous material to crosslink to produce said phase invertible composition, wherein the polyamine and the proteinaceous material crosslink only in the presence of the crosslinking composition to form the phase invertible composition; wherein the phase invertible composition is exposed to radiation, wherein said substrate has a kinematic viscosity of about 70 to 200 centistokes and wherein the crosslinking agent comprises a reaction product of an excess of a liquid aldehyde crosslinking agent and a glycosaminoglycan.
2. A method as in claim 1 , wherein the radiation sterilizes the phase invertible composition.
3. A method as in claim 1 , wherein the radiation comprises gamma radiation.
4. A method as in claim 1 , wherein the radiation comprises electron beam radiation.
5. A method as in claim 1 , wherein said polyamine is a polyalkylenimine.
6. A method as in claim 5 , wherein said polyalkyenimine is a polyethylenimine.
7. A method as in claim 5 , wherein said polyethylenimine is a branched polyethylenimine.
8. A method as in claim 7 , wherein the weight ratio of branched polyethylenimine to proteinaceous material is about 1:5 to 80.
9. A method as in claim 1 , wherein said substrate further comprises a carbohydrate.
10. The method as in claim 9 , wherein said carbohydrate is chitosan.
11. A method as in claim 1 , wherein said crosslinking agent comprises an aldehyde.
12. A method as in claim 11 , wherein said aldehyde is glutaraldehyde.
13. A method as in claim 12 , wherein said glutaraldehyde is heat stabilized.
14. A method as in claim 1 , wherein crosslinking agent comprises a macromolecular crosslinking agent.
15. A method as in claim 1 , wherein said glycosaminoglycan is hyaluronan.
16. A method as in claim 1 , wherein the viscosity of said substrate approximates that of said crosslinker.
17. A method as in claim 16 , wherein said crosslinker further comprises a viscosity modifying agent.
18. A method as in claim 1 , wherein said proteinaceous material is selected from the group consisting of: albumin, elastin, fibrin and soluble and insoluble forms of collagen and combinations thereof.
19. A method as in claim 1 , wherein said substrate further comprises an agent selected from the group consisting of a tackifying agent, and a plasticizing agent.
20. A method as in claim 1 , wherein said crosslinking agent further comprises an agent selected from the group consisting of a tackifying agent, and a plasticizing agent.
21. The method of claim 10 , wherein the substrate comprises about 0.1% (w/w) to about 5% (w/w) chitosan.
22. The method of claim 10 , wherein the substrate comprises about 0.1% (w/w) to about 0.3% (w/w) chitosan.
23. The method of claim 10 , wherein the substrate comprises about 0.16% (w/w) chitosan.