Adhesive complex coacervates and method of making and using thereof

Patent metadata

Field	Value
Publication number	US-9913926-B2
Application number	US-201213617882-A
Country	US
Kind code	B2
Filing date	Sep 14, 2012
Priority date	Jan 24, 2008
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

Described herein is the synthesis of adhesive complex coacervates and their use thereof. The adhesive complex coacervates are composed of a mixture of one or more polycations and one or more polyanions. The polycations and polyanions in the adhesive complex coacervate are crosslinked with one another by covalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applications. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. They have numerous biological applications as bioadhesives and drug delivery devices and are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.

First claim

What is claimed:

1. An adhesive comprising a fluid complex coacervate, wherein the complex coacervate comprises a polyamino compound and a polyphosphate compound, wherein each polyamino compound and polyphosphate compound includes at least one fragment having the formula VII

wherein R 1 , R 2 , and R 3 are, independently, hydrogen or an alkyl group, X is oxygen or NR 5 , where R 5 is hydrogen or an alkyl group, and m is from 1 to 10, or the pharmaceutically-acceptable salt thereof, wherein at least one of R 2 or R 3 is an acrylate group or a methacrylate group, wherein the acrylate group or methacrylate group on the polyamino compound and polyphosphate compound are capable of covalently crosslinking with one another, and wherein the complex coacervate does not include a multivalent cation.

2. The coacervate of claim 1 , wherein the polyphosphate compound comprises a polymer comprising at least one fragment comprising the formula II

wherein R 4 is hydrogen or an alkyl group, and n is from 1 to 10, or the pharmaceutically-acceptable salt thereof.

3. The coacervate of claim 1 , wherein the polyphosphate compound comprises at least one dihydroxyl aromatic group capable of undergoing oxidation, wherein the dihydroxyl aromatic group is covalently attached to the polyphosphate compound.

4. The coacervate of claim 1 , wherein the coacervate further comprises one or more bioactive agents encapsulated in the complex.

5. The coacervate of claim 1 , wherein the coacervate further comprises a stabilized oxidant complex.

6. An adhesive produced by the process comprising
(a) heating an adhesive complex coacervate of claim 1 , wherein upon heating the adhesive complex coacervate the coacervate is converted to an insoluble solid; and
(b) covalently crosslinking the polyphosphate compound and polyamino compound in the insoluble solid to produce the adhesive.

7. An adhesive produced by the process comprising
(a) preparing an adhesive complex coacervate of claim 1 ;
(b) adjusting the pH of the adhesive complex coacervate to produce an insoluble solid; and
(c) covalently crosslinking the polyamino compound and polyphosphate compound in the insoluble solid to produce the adhesive.

8. A method for repairing a bone fracture in a subject, comprising contacting the fractured bone with the adhesive complex coacervate of claim 1 .

9. A method for adhering a metal substrate to a bone of a subject comprising contacting the bone with the adhesive complex coacervate of claim 1 and applying the metal substrate to the coated bone.

10. A method for adhering a bone-tissue scaffold to a bone of a subject comprising contacting the bone and tissue with the adhesive complex coacervate of claim 1 and applying the bone-tissue scaffold to the bone and tissue.

11. A method for delivering one or more bioactive agents comprising administering the adhesive complex coacervate of claim 1 to a subject.

12. A method for repairing a corneal laceration in a subject, comprising applying to the laceration the adhesive complex coacervate of claim 1 .

13. A method for inhibiting blood flow in a blood vessel of a subject comprising introducing the adhesive complex coacervate of claim 1 into the vessel.

14. The coacervate of claim 1 , wherein the coacervate has a pH greater than or equal to 7.0.

15. The coacervate of claim 1 , wherein the coacervate has a pH from 7. 0 to 9.0.

16. The coacervate of claim 1 , wherein R 2 is hydrogen and R 3 is an acrylate or methacrylate group.

17. The coacervate of claim 1 , wherein R 1 is methyl, R 2 is hydrogen, R 3 is an acrylate or methacrylate group, X is NH, and m is 2.

18. The coacervate of claim 1 , wherein the polyamino compound has at least one fragment of the formula I

wherein R 1 , R 2 , and R 3 are, independently, hydrogen or an alkyl group, X is oxygen or NR 5 , where R 5 is hydrogen or an alkyl group, and m is from 1 to 10, or the pharmaceutically-acceptable salt thereof.

Assignees

• Stewart Russell J
• Shao Hui
• Univ Utah Res Found

Inventors

• Stewart Russell J
• Shao Hui

Classifications

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• C08F8/06

  Oxidation · CPC title

• C08F2810/20

  leading to a crosslinking, either explicitly or inherently · CPC title

• A61L27/26

  Mixtures of macromolecular compounds · CPC title

• A61L2300/602

  Type of release, e.g. controlled, sustained, slow · CPC title