Reinforced adhesive complex coacervates and methods of making and using thereof

• US 10,653,813 B2
• Filed: 12/06/2017
• Issued: 05/19/2020
• Est. Priority Date: 05/24/2010
• Status: Active Grant

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Stewart, Russell J.
• Primary Examiner(s): Pipic, Alma
• Application Number:
  US15/833,157
• Publication Number:
  US 20180099070A1
• Time in Patent Office: 895 Days
• CPC Class Codes: A61L 2300/62 Encapsulated active agents, e.g. emulsified droplets
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/02 containing inorganic materials
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 24/06 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043, A61L24/046 take precedence
• CPC Class Codes: A61L 24/10 Polypeptides; Proteins A61L24/043 takes precedence
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C
• CPC Class Codes: C08F 8/06 Oxidation
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00

Abstract

Described herein is the synthesis of reinforced adhesive complex coacervates and their use thereof. The reinforced adhesive complex coacervates are composed of (a) at least one polycation, (b) at least one polyanion, and (c) a reinforcing component. The adhesive complex coacervates described herein can be subsequently cured to produce strong, cohesive adhesives. The reinforced adhesive complex coacervates have several desirable features when compared to conventional adhesives. The reinforced adhesive complex coacervates are effective in wet or underwater applications. The reinforced adhesive complex coacervates described herein, being phase separated from water, can be applied underwater without dissolving or dispersing into the water. The reinforced adhesive complex coacervates have numerous biological applications as bioadhesives and bioactive delivery devices. In particular, the reinforced adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, wet tissues in physiological conditions.

Claims

1. An associative liquid adhesive complex coacervate, wherein the liquid adhesive complex coacervate comprises (a) at least one polycation, (b) at least one polyanion, and (c) a reinforcing component comprising a water-insoluble solid.

2. The associative liquid adhesive complex coacervate of claim 1, wherein the polycation comprises a polyamino compound.

3. The associative liquid adhesive complex coacervate of claim 1, wherein the polycation comprises a polysaccharide, a natural protein, a recombinant protein, or a synthetic polyamine.

4. The associative liquid adhesive complex coacervate of claim 1, wherein the polycation comprises an alkylamino group, a heteroaryl group, a guanidinyl group, or an aromatic group substituted with one or more amino groups.

5. The associative liquid adhesive complex coacervate of claim 1, wherein the polycation comprises a natural protein.

6. The associative liquid adhesive complex coacervate of claim 5, wherein the natural protein comprises one or more guanidinyl groups.

7. The associative liquid adhesive complex coacervate of claim 1, wherein the polycation comprises a polymer comprising at least one fragment comprising the formula I

8. The associative liquid adhesive complex coacervate of claim 7, wherein R¹, R², and R³ are methyl, X is O, and m is 3.

9. The associative liquid adhesive complex coacervate of claim 1, wherein the polyanion comprises two or more sulfate, sulfonate, carboxylate, borate, boronate, phosphonate, or phosphate groups.

10. The associative liquid adhesive complex coacervate of claim 1, wherein the polyanion comprises a polyphosphate.

11. The associative liquid adhesive complex coacervate of claim 10, wherein the polyphosphate comprises a natural polymer or a synthetic polymer.

12. The associative liquid adhesive complex coacervate of claim 10, wherein the polyphosphate comprises a polyacrylate comprising one or more pendant phosphate groups.

13. The associative liquid adhesive complex coacervate of claim 1, wherein the polyanion comprises a polymer comprising at least one fragment comprising the formula X

14. The associative liquid adhesive complex coacervate of claim 13, wherein Z is sulfate, sulfonate, carboxylate, borate, boronate, a substituted or unsubstituted phosphate, or a phosphonate.

15. The associative liquid adhesive complex coacervate of claim 1, wherein the polyanion comprises a polymer comprising at least one fragment comprising the formula II

16. The associative liquid adhesive complex coacervate of claim 15, wherein R⁴ is methyl and n is 2.

17. The associative liquid adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a particle, wherein the particle comprises a metal oxide, a ceramic particle, a silica particle, or a water insoluble inorganic salt.

18. The associative liquid adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a fiber.

19. The associative liquid adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a metal oxide particle.

20. The associative liquid adhesive complex coacervate of claim 1, wherein the reinforcing component comprises a metal particle.

21. The associative liquid adhesive complex coacervate of claim 20, wherein the metal particle is platinum, gold, or tantalum.

22. The associative liquid adhesive complex coacervate of claim 1, wherein the polycation comprises a natural protein comprising one or more guanidinyl groups, the polyanion comprises a polyphosphate, and the reinforcing component comprises a metal particle.

23. The associative liquid adhesive complex coacervate of claim 1, wherein the associative liquid adhesive complex coacervate further comprises a bioactive agent selected from the group consisting of a nucleic acid, an antibiotic, a pain reliever, an immune modulator, a growth factor, an enzyme inhibitor, a hormone, a mediator, a messenger molecule, a cell signaling molecule, a receptor agonist, and a receptor antagonist, wherein the bioactive agent is encapsulated in the associative liquid adhesive complex coacervate.