Trehalose hydrogels for stabilization and delivery of proteins

Patent metadata

Field	Value
Publication number	US-10662295-B2
Application number	US-201515503348-A
Country	US
Kind code	B2
Filing date	Aug 12, 2015
Priority date	Aug 12, 2014
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

Trehalose-based hydrogels and methods of making such hydrogels are disclosed. Specifically, a method of creating a trehalose-based hydrogel, comprising the steps of: a) forming a trehalose homopolymer or co-polymer; b) preparing a cross-linker; and c) reacting the trehalose homopolymer or co-polymer with the cross-linker to form the trehalose-based hydrogel.

First claim

I claim:

1. A method of creating a trehalose-based hydrogel, comprising the steps of:
a) preparing a trehalose cross-linker;
b) preparing a trehalose-based monomer; and
c) reacting a mixture comprising the trehalose cross-linker and the trehalose-based monomer to form the trehalose-based hydrogel,
wherein the trehalose cross-linker is synthesized using identical chemistry as is used to prepare the trehalose-based monomer
wherein the mixture has a molar ratio of the trehalose-based monomer to the trehalose cross-linker of 18.96-50
wherein—
(i) the trehalose cross-linker has the structure

and the trehalose-based monomer has the structure

or
(ii) the trehalose cross-linker comprises the structure

and the trehalose-based monomer has the structure

2. The method according to claim 1 , wherein the trehalose cross-linker is synthesized during the same step as that is used to prepare the trehalose-based monomer.

3. The method according to claim 1 , wherein the reaction in step c) is Free Radical Polymerization initiated by a Redox initiator.

4. The method according to claim 1 , wherein the trehalose cross-linker has the structure

and the trehalose-based monomer has the structure

5. The method according to claim 1 , wherein the trehalose cross-linker comprises the structure

and wherein the trehalose-based monomer has the structure

6. The method according to claim 1 , wherein no HPLC purification process to purify the trehalose-based monomer is needed.

7. A method of stabilizing a protein, comprising the steps of:
a) preparing a trehalose-based hydrogel according to the method from claim 1 ; and
b) adding a protein into the trehalose-based hydrogel either at the time of hydrogel formation or after the formation to form a complex of the protein and the trehalose-based hydrogel;
wherein the protein is stabilized.

8. The method according to claim 7 , wherein the protein is an enzyme.

9. The method according to claim 7 , wherein the protein is stabilized when exposed to heat.

10. The method according to claim 9 , wherein the protein is stabilized above 4° C.

11. The method according to claim 10 , wherein the protein is stabilized at 70-90° C.

12. The method according to claim 7 , wherein the protein is released from the complex of the protein and the trehalose-based hydrogel by diluting with water or lowering the pH.

Assignees

• Univ California

Inventors

• Maynard Heather D

Classifications

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C12N9/16

  acting on ester bonds (3.1) · CPC title

• C12Y301/03026

  4-Phytase (3.1.3.26), i.e. 6-phytase · CPC title