Biofunctional hydrogel for wound healing

Patent metadata

Field	Value
Publication number	US-12097300-B2
Application number	US-202117167568-A
Country	US
Kind code	B2
Filing date	Feb 4, 2021
Priority date	Feb 7, 2020
Publication date	Sep 24, 2024
Grant date	Sep 24, 2024

Abstract

Disclosed herein is a hydrogel that eradicates biofilm bacteria from wounds and accelerates diabetic wound healing. Also disclosed herein are methods of manufacture and use of said hydrogel.

First claim

The invention claimed is:

1. A hydrogel for wound healing comprising:
a hydrogel polymeric matrix comprising:
a first polymeric component;
a second polymeric component, where the first and second polymeric components are crosslinked together to form the hydrogel polymeric matrix; and
a first portion of a polymeric antimicrobial material capable of crosslinking with the first and/or second polymeric components, said first portion being wholly or partly crosslinked into the hydrogel polymeric matrix;
a second portion of the polymeric antimicrobial material capable of crosslinking with the first and/or second polymeric components, said second portion being distributed within the hydrogel polymeric matrix but not crosslinked into the hydrogel polymeric matrix;
wherein the first and second polymeric components are selected from one of the following sets:
(a) the first polymeric component is derived from a polymeric material comprising at least two thiol functional groups and the second polymeric component is derived from a polymeric material comprising at least two maleimide groups;
(b) the first polymeric component is derived from a polymeric material comprising at least two thiol functional groups and the second polymeric component is derived from a polymeric material comprising at least two vinyl sulfone groups;
(c) the first polymeric component is derived from a polymeric material comprising at least two azide functional groups and the second polymeric component is derived from a polymeric material comprising at least two cyclooctynyl groups;
(d) the first polymeric component is derived from a polymeric material comprising at least two amine functional groups and the second polymeric component is derived from a polymeric material comprising at least two aldehyde groups; and
(e) the first polymeric component is derived from a polymeric material comprising at least two amine functional groups and the second polymeric component is derived from a polymeric material comprising at least two acrylate groups; and

optionally, an antioxidant material distributed within the hydrogel polymeric matrix and/or covalently bonded thereto.

2. The hydrogel according to claim 1 , wherein the first polymeric component is derived from a polymeric material comprising at least two thiol functional groups and the second polymeric component is derived from a polymeric material comprising at least two maleimide groups.

3. The hydrogel according to claim 2 , wherein the first polymeric component is derived from a polymeric material that has from 2 to 8 thiol functional groups and the second polymeric component is derived from a polymeric material that has from 2 to 8 maleimide groups.

4. The hydrogel according to claim 3 , wherein the first polymeric component is derived from a multi-arm polyethylene glycol having from 2 to 8 arms that are each terminated by a thiol functional group and the second polymeric component is derived from a multi-arm polyethylene glycol having from 2 to 8 arms that are each terminated by a maleimide group.

5. The hydrogel according to claim 4 , wherein the first polymeric component is derived from poly(ethylene glycol) tetra thiol and the second polymeric component is derived from poly(ethylene glycol) tetra maleimide.

6. The hydrogel according to claim 1 , wherein the polymeric antimicrobial material capable of crosslinking with the first and/or second polymeric components is selected from one or more of
a polycationic polymer terminated by at least two maleimide groups,
a polycationic polymer terminated by at least one maleimide group and at least one thiol group,
a polycationic polymer terminated by at least two vinyl sulfone groups,
a polycationic polymer terminated by at least one vinyl sulfone group and at least one thiol group,
a polycationic polymer terminated by at least two cyclooctynyl groups,
a polycationic polymer terminated by at least two azide groups,
a polycationic polymer terminated by at least one cyclooctynyl group and at least one azide group,
a polycationic polymer terminated by at least two amino groups,
a polycationic polymer terminated by at least two aldehyde groups,
a polycationic polymer terminated by at least one amino group and at least one aldehyde group,
a polycationic polymer terminated by at least two acrylate groups, and
a polycationic polymer terminated by at least one amino group and at least one acrylate group provided that said material is capable of forming a crosslink with at least one of the first and second polymeric components.

7. The hydrogel according to claim 1 , wherein the polymeric antimicrobial material is a polycationic polymer terminated by at least two maleimide groups.

8. The hydrogel according to claim 7 , wherein the polymeric antimicrobial material is a polyimidazolium polymer terminated by two maleimide groups.

9. The hydrogel according to claim 1 , wherein the polymeric antimicrobial material capable of crosslinking with the first and/or second polymeric components has a number average molecular weight of from 500 Daltons to 50,000 Daltons.

10. The hydrogel according to claim 9 , wherein the polymeric antimicrobial material has a number average molecular weight of from 1,000 Daltons to 15,000 Daltons.

11. The hydrogel according to claim 10 , wherein the polymeric antimicrobial material has a number average molecular weight of from 2,000 Daltons to 10,000 Daltons.

12. The hydrogel according to claim 1 , wherein the antioxidant material is present and is N-acetyl cysteine.

13. The hydrogel according to claim 1 , wherein the hydrogel is in a form selected from a film, nanoparticles and microparticles.

14. A composite material comprising a substrate and a coating formed of a hydrogel as described in claim 1 .

15. A kit of parts selected from:
(i) (ia) a first mixture comprising a first polymer capable of crosslinking with a second polymer and, optionally, an antioxidant material as described in claim 1 ;
(ib) a second mixture comprising a second polymer and a polymeric antimicrobial material capable of crosslinking with the first polymer; and
(ic) a pharmaceutically acceptable solvent;
or

(ii) (iia) a first mixture comprising a first polymer capable of crosslinking with a second polymer, and a polymeric antimicrobial material capable of crosslinking with the second polymer, and, optionally, an antioxidant material as described in claim 1 ;
(iib) a second mixture comprising a second polymer; and
(iic) a pharmaceutically acceptable solvent;
or

(iii) (iiia) a first mixture comprising a first polymer capable of crosslinking with a second polymer and a polymeric antimicrobial material capable of crosslinking with the second polymer;
(iiib) a second mixture comprising a second polymer and, optionally, an antioxidant material as described in claim 1 ; and
(iiic) a pharmaceutically acceptable solvent;
or

(iv) (iva) a first mixture comprising a first polymer capable of crosslinking with a second polymer and, optionally, an antioxidant material as described in claim 1 ;
(ivb) a second mixture comprising a second polymer;
(ivc) a pharmaceutically acceptable solvent; and
(ivd) a polymeric antimicrobial material capable of crosslinking with the first and second polymers.

16. A method of forming a hydrogel according to claim 1 , comprising the steps of:
(AA) providing at least two separate solutions, each of said solutions containing a solvent, where each of the at least two solutions contain one or more of a first polymer capable of crosslinking with a second polymer, a second polymer capable o

Assignees

• Univ Nanyang Tech

Inventors

• Chan Bee Eng Mary
• Yeo Chun Kiat
• Tan Nguan Soon
• Mahadevegowda Surendra Hittanahalli

Classifications

• C08L81/02

  Polythioethers; Polythioether-ethers · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• C08L79/04

  Polycondensates having nitrogen-containing heterocyclic rings in the main chain; Polyhydrazides; Polyamide acids or similar polyimide precursors · CPC title

• A61L2400/12

  Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces · CPC title

• A61L26/0052

  Mixtures of macromolecular compounds · CPC title