Dissolvable hydrogel compositions for wound management and methods of use

Patent metadata

Field	Value
Publication number	US-2016287745-A1
Application number	US-201414901858-A
Country	US
Kind code	A1
Filing date	Jun 30, 2014
Priority date	Jul 1, 2013
Publication date	Oct 6, 2016
Grant date	—

Abstract

The inventions provided herein relate to dissolvable hydrogel compositions and methods of uses, e.g., but not limited to, in wound management. Accordingly, methods for wound management involving the dissolvable hydrogel compositions are also provided herein. In some embodiments, the dissolvable hydrogel composition comprises an adhesive thioester hydrogel, which can facilitate adherence of the dissolvable hydrogen composition to a surface (e.g., a wound) and can be controllably dissolved later upon addition of a thiolate compound to release the dissolvable hydrogel composition from the surface (e.g., the wound).

First claim

What is claimed is:

1 . A method comprising:
(a) contacting a wound with a hydrogel composition comprising a dissolvable hydrogel layer, wherein the dissolvable hydrogel layer comprises linear, branched, and/or dendritic crosslinkable polymers held together by covalent bonds formed between the first crosslinkable polymer and the second crosslinkable polymer, wherein the dissolvable hydrogel layer comprises thioester linkages; and (b) allowing the dissolvable hydrogel layer to adhere to tissue surrounding the wound.

2 . The method of claim 1 , further comprising dissolving the dissolvable hydrogel layer by adding a thiolate compound to result in a thiol-thioester exchange, thereby releasing the hydrogel composition from the wound.

3 . A method comprising:
(a) contacting a wound with a hydrogel composition comprising a dissolvable hydrogel layer, wherein the dissolvable hydrogel layer comprises linear, branched, and/or dendritic crosslinkable polymers held together by thioester linkages formed between the first crosslinkable polymer and the second crosslinkable polymer; (b) allowing the dissolvable hydrogel layer to adhere to tissue surrounding the wound; and (c) dissolving the dissolvable hydrogel layer by adding a thiolate compound to result in a thiol-thioester exchange, thereby releasing the hydrogel composition from the wound.

4 . The method of any of claims 1 - 3 , wherein the dissolvable hydrogel layer is derived from a first water-soluble linear, branched, and/or dendritic crosslinkable polymer comprising at least two thiol moieties and a second water-soluble linear, branched, and/or dendritic crosslinkable polymer comprising at least two crosslinking moieties that are capable of reacting with said at least two thiol moieties of the first crosslinkable polymer to form the thioester linkages between the first and second crosslinkable polymers.

5 . The method of claim 1 or 2 , wherein the dissolvable hydrogel layer is derived from a first water-soluble linear, branched, and/or dendritic crosslinkable polymer comprising at least two thioester linkages and a second water-soluble linear, branched, and/or dendritic crosslinkable polymer comprising at least two crosslinking moieties that are capable of forming a linkage with the first water-soluble linear, branched, and/or dendritic polymer.

6 . The method of claim 1 or 2 , wherein the dissolvable hydrogel layer is derived from a first water-soluble linear, branched and/or dendritic crosslinkable polymer comprising at least two nucleophilic moieties that are capable of forming a linkage with at least two crosslinking moieties of the second-water soluble linear, branched and/or dendritic polymer; wherein at least one of the first and second water-soluble linear, branched and/or dendritic crosslinkable polymers comprises at least two thioester linkages.

7 . The method of any of claims 1 - 6 , wherein the linear crosslinkable polymer comprises polyesters, polyethers, polyether-esters, polyglycerols, polyamino acids, polyester-amines, polyurethanes, polycarbonates, polyamino alcohols, thiols, amines, N-hydroxysuccinimide (NHS) moieties, maleimide (MAL) moieties, or any combinations thereof.

8 . The method of any of claims 1 - 7 , wherein the branched crosslinkable polymer comprises polyesters, polyethers, polyether-esters, polyglycerols, polyamino acids, polyester-amines, polyurethanes, polycarbonates, polyamino alcohols, thiols, amines, N-hydroxysuccinimide (NHS) moieties, Maleimide (MAL) moieties, or any combinations thereof.

9 . The method of any of claims 1 - 8 , wherein the dendritic crosslinkable polymer comprises polyesters, polyethers, polyether-esters, polyamino acids, polyester-amines, polyurethanes, polycarbonates, polyamino alcohols, thiols, amines, N-hydroxysuccinimide (NHS) moieties, Maleimide (MAL) moieties, or any combinations thereof.

10 . The method of any of claims 1 - 9 , wherein the first crosslinkable polymer has a chemical structure selected from the group consisting of structure (i)-structure (xii) shown as follows:

and any combinations thereof; and wherein:
Q is independently selected from the group consisting of O, S, Se, NH, CH 2 and any combination thereof;
R is selected from the group consisting of a hydrogen, straight or branched alkyl, cycloalkyl, aryl, olefin or alkene, alkyne, silyl, alkylsilyl, arylsilyl, alkylaryl or arylalkyl chain of 1-50 carbons, fluorocarbon, and any combinations thereof, wherein each alkyl, cycloalkyl, aryl, olefin, alkyne, silyl, alkylsilyl, arylsilyl, alkylaryl, fluorocarbon, or arylalkyl chain is optionally substituted internally or terminally by one or more hydroxyl, hydroxyether, carboxyl, carboxyester, carboxyamide, amino, mono- or di-substituted amino, thiol, thioester, sulfate, phosphate, phosphonate, halogen substituents; and any combinations thereof; and
m, n, and x are each independently selected from an integer of 0-1000.

11 . The method of any of claims 4 - 10 , wherein said at least two crosslinking moieties comprise at least one N-hydroxysuccinimide (NHS) or maleimide (MAL) moeity.

12 . The method of any of claims 4 - 10 , wherein said at least two crosslinking moieties comprise at least two N-hydroxysuccinimide (NHS) or maleimide (MAL) moeities.

13 . The method of any of claims 1 - 12 , wherein the second cross-linkable polymer has a chemical structure selected from the group consisting of structure (xiii)-structure (xl) shown as follows:

and any combination thereof; and wherein
Q is independently selected from the group consisting of O, S, Se, NH, CH 2 and any combination thereof;
R is selected from the group consisting of a hydrogen, straight or branched alkyl, cycloalkyl, aryl, olefin or alkene, alkyne, silyl, alkylsilyl, arylsilyl, alkylaryl or arylalkyl chain of 1-50 carbons, fluorocarbon, and any combinations thereof, wherein each alkyl, cycloalkyl, aryl, olefin, alkyne, silyl, alkylsilyl, arylsilyl, alkylaryl, fluorocarbon,

Assignees

• Univ Boston

Inventors

• Grinstaff Mark W
• Ghobril Cynthia
• Wathier Michel Christophe
• Konieczynska Marlena Dagmara

Classifications

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L26/008 Primary

  Hydrogels or hydrocolloids · CPC title

• A61L24/0015

  Medicaments; Biocides · CPC title

• A61L15/60

  Liquid-swellable gel-forming materials, e.g. super-absorbents · CPC title

• A61L26/0066

  Medicaments; Biocides · CPC title