IP Library › Granted Patent US 10,494,538
Granted Patent B2
US 10,494,538 · App. 14/893,561 · Granted Dec 3, 2019

Switchable antimicrobial and antifouling carboxybetaine-based hydrogels and elastomers with enhanced mechanical properties

Inventors: Gang Cheng (Fairlawn, OH); Bin Cao (Akron, OH)
Assignee: THE UNIVERSITY OF AKRON
C09D133/14A01N37/12C07C227/02C07C227/16C07C227/18C07C229/12C07C233/38C08F20/34C08F20/36C08F22/385C08F120/36C08F220/36C08F222/385C09D5/14C09D133/26C09D139/00
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Quick Facts
Patent No.
US 10,494,538
App. No.
14/893,561
Granted
Dec 3, 2019
Kind
B2
Abstract

Various embodiments of the present invention are directed to switchable carboxybetaine-based polymers, hydrogels, and/or elastomers, along with novel related monomers, crosslinkers, and methods. Under acidic conditions, the materials undergo self-cyclization and can catch and kill bacteria. Under neutral/basic conditions, these materials undergo ring-opening and can release killed bacterial cells and resist protein adsorption and bacterial attachment. These smart polymers, hydrogels and elastomers also show excellent mechanical properties making them highly desirable for many biomedical applications.

Claims (41)

1. A zwitterionic composition having anti-fouling and antimicrobial properties comprising:

a polymer backbone formed from monomers selected from the group consisting of acrylates, methacrylates, acrylamides, methacrylamides, vinyl alcohols, serines and combinations thereof;

one or more zwitterionic moieties chemically bonded to said polymer backbone, said zwitterionic moieties further comprising a carboxybetaine group having at least one ethanol, propanol, butanol or pentanol group bonded to the nitrogen atom of said carboxybetaine group; and

a crosslinking compound.

2. The zwitterionic composition of claim 1 wherein said polymer backbone is selected from the group consisting of polymethacrylate, polyethylacrylate, polymethacrylamide, polyethylacrylamide poly(2-hydroxyethyl methacrylate), polyserine, polyvinyl alcohol, and combinations thereof.

3. The zwitterionic composition of claim 1 wherein said one or more zwitterionic moieties have a formula selected from the group consisting of:

wherein is the polymer backbone.

4. The zwitterionic composition of claim 1 having the formula:

wherein R 1 is H, —CH 3 or —CH 2 CH 3 ; R 2 are O or NH; R 3 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; R 4 is —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 5 is H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or CH 2 CH 2 CH 2 CH 2 CH 2 OH; and R 6 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 — and n is an integer from 2 to 10,000.

5. The zwitterionic composition of claim 1 wherein said one or more zwitterionic moieties have a formula:

wherein R 1 is O or NH; R 2 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; R 3 is —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 4 is H, —CH 3 , CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 5 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 — and is the polymer backbone.

6. The zwitterionic composition of claim 1 wherein said one or more zwitterionic moieties have a formula:

wherein R 1 is O or NH; R 2 is —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 3 is H, —CH 3 , CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH, R 4 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; and is the polymer backbone.

7. The zwitterionic composition of claim 1 wherein said one or more zwitterionic moieties have the formula:

wherein R 1 is —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 2 are H, —CH 3 , CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R3 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; and is the polymer backbone.

8. The zwitterionic composition of claim 1 wherein said one or more zwitterionic moieties are selected from the group consisting of 2-(bis(2-hydroxyethyl)(methylene)ammonio)acetate, 2-((2-hydroxyethyl)(methylene)(methyl)ammonio)acetate, 2-((2-hydroxyethyl)(methylene)ammonio)acetate, 3-(bis(2-hydroxyethyl)(methylene) (methyl)ammonio)propanoate, 3-((2-hydroxyethyl)(methylene) (methyl)ammonio)propanoate, 3-((2-hydroxyethyl)(methylene)ammonio) propanoate and combinations thereof.

9. A chemical composition comprising the zwitterionic composition of claim 1 wherein said each of the one or more zwitterionic moieties has a corresponding cationic ring form.

10. The chemical composition of claim 9 wherein the cationic ring form has the formula:

wherein R 1 is O or NH; R 2 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; R 3 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 4 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 CH 2 —; R is any organic or inorganic anion; and is the polymer backbone.

11. The chemical composition of claim 9 wherein the cationic ring form of said one or more zwitterionic moieties has the formula:

wherein R 1 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 2 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; R is any organic or inorganic anion; and is the polymer backbone.

12. The chemical composition of claim 9 wherein the cationic ring form of the one or more zwitterionic moieties has a formula selected from the group consisting of:

wherein R − is any organic or inorganic anion and is the polymer backbone.

13. The zwitterionic composition of claim 1 wherein said crosslinking compound comprises a compound selected from the group consisting of di(methyl)acrylate, multi-(methyl)acrylate, di(methyl)acrylamide, multi-(methyl)acrylamide, diepoxide, multi-epoxide, dithiol and multi-thiol, and combinations thereof.

14. The zwitterionic composition of claim 1 wherein said crosslinking compound has the formula:

wherein R 1 and R 7 are —H, —CH 3 , or —CH 2 CH 3 ; R 2 and R 6 are O or NH; R 3 and R 5 are —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; R 4 —H, CH 3 , CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; and R 8 is —CH 2 − , —CH 2 CH 2 − , —CH 2 CH 2 CH 2 − , —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —.

15. The zwitterionic composition of claim 1 wherein said one or more crosslinking compound is selected from the group consisting of carboxybetaine di(methyl)acrylate, carboxybetaine di(methyl)acrylamide, poly(ethylene glycol) di(methyl)acrylate, 1,3-propanedithiol, 1,4-butanedithiol, 1,3-butadiene diepoxide, and combinations thereof.

16. The zwitterionic composition of claim 1 wherein said one or more crosslinking compound has the formula:

17. A carboxybetaine-based composition having anti-fouling and antimicrobial properties comprising:

a zwitterionic polymer selected from the group consisting of poly(2-((2-hydroxyethyl)(2-methacrylamidoethyl)(methyl)ammonio)acetate), poly(3-((2-hydroxyethyl)(2-methacrylamidoethyl)(methyl)ammonio)propanoate), poly(2-((2-hydroxyethyl)(2-(methacryloyloxy)ethyl)(methyl)ammonio)acetate) and poly(2-(bis(2-hydroxyethyl)(2-(methacryloyloxy)ethyl)ammonio)acetate) and combinations thereof; and

a crosslinker.

18. The carboxybetaine composition of claim 17 wherein the crosslinker selected from the group consisting of carboxybetaine di(methyl)acrylate, carboxybetaine di(methyl)acrylamide, poly(ethylene glycol) di(methyl)acrylate, 1,3-propanedithiol, 1,4-butanedithiol, 1,3-butadiene diepoxide, and combinations thereof.

19. The zwitterionic composition of claim 17 wherein said one or more crosslinker has the formula:

20. The carboxybetaine composition of claim 17 wherein the crosslinker has the formula:

wherein R 1 and R 5 are H, —CH 3 , or —CH 2 CH 3 ; R 2 and R 4 are O or NH; R 3 is H, —CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 O—COCH═CH 2 , —CH 2 CH 2 O—COC(CH 3 )═CH 2 , —CH 2 CH 2 NH—COCH═CH 2 , or —CH 2 CH 2 NH—COC(CH 3 )═CH 2 and R 6 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 CH 2 —.

21. The carboxybetaine composition of claim 17 wherein the crosslinker has the formula:

where R 1 and R 7 are —H, —CH 3 , or —CH 2 CH 3 ; R 2 and R 6 are O or NH; R 3 and R 5 are —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; R 4 is —H, CH 3 , CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; and R 8 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —.

22. The zwitterionic composition of claim 1 wherein one or more of the monomers that form the polymer backbone has the formula:

where R 1 is —H, —CH 3 , or —CH 2 CH 3 ; R 2 is O or NH; R 3 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —; R 4 is —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 5 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or CH 2 CH 2 CH 2 CH 2 CH 2 OH; and R 6 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —.

23. The zwitterionic composition of claim 1 wherein one or more of the monomers that form the polymer backbone has the formula:

where R 1 is —H, —CH 3 , —CH 2 CH 3 ; R 2 is O or NH; R 3 is —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or —CH 2 CH 2 CH 2 CH 2 CH 2 OH; R 4 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 CH 2 CH 2 OH, or CH 2 CH 2 CH 2 CH 2 CH 2 OH; and R 5 is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 26, 2017
From: CHENG, GANG; CAO, BIN
To: THE UNIVERSITY OF AKRON
Reel/Frame 043688/0880 →
Continuity (3)
Provisional Application 61828782 · May 30, 2013
Provisional Application 61866222 · Aug 15, 2013
Related Publication 20170362458A1 · Dec 21, 2017