Granted Patent B2

US 12,746,277 · App. 18/729,853 · Granted Sep 29, 2026

Inventors: Matthew Webber (South Bend, IN); Yuanhui Xiang (South Bend, IN); Sijie Xian (South Bend, IN)

Assignee: UNIVERSITY OF NOTRE DAME DU LAC

A61K38/28A61K47/24A61K47/595A61K47/61A61K47/6903A61P3/10

Abstract

Claims (57)

1 . A hydrogel, the hydrogel comprising:

(i) a diboronate compound of formula (I):

wherein:

 wherein:

R 1 , at each occurrence, is independently C 1-4 alkyl, cyclopropyl, C 1-2 fluoroalkyl, —F, —CN, or —NO 2 ;

R 2 , at each occurrence, is independently C 1-4 alkyl, cyclopropyl, C 1-2 fluoroalkyl, —F, —CN, or —NO 2 ;

X ⊖ is an anion having a net charge of −1;

 is a linking moiety; and

 is a first moiety comprising a hydrophilic polymer, a hyperbranched macromolecule, or a combination thereof; and

(ii) a diol compound of formula (II):

wherein:

 is a second moiety comprising a hydrophilic polymer, a hyperbranched macromolecule, or a combination thereof;

wherein the diboronate compound of formula (I) and the diol compound of formula (II) form crosslinks by dynamic-covalent bonds.

2 . The hydrogel of claim 1 , wherein

3 . The hydrogel of claim 1 , wherein

4 . The hydrogel of claim 1 , wherein X ⊖ is Br − , Cl − , NO 3 − , H 2 PO 4 − , H 2 PO 3 − , HSO 4 − , HSO 3 − , H 3 C—SO 3 − , HCO 3 − , HCO 2 − , H 3 C—CO 2 − , HC 2 O 4 − , or TsO − .

5 . The hydrogel of claim 1 , wherein X ⊖ is Br − or Cl − .

6 . The hydrogel of claim 1 , wherein

7 . The hydrogel of claim 1 , wherein

8 . The hydrogel of claim 1 , wherein

has an equilibrium constant (K eq ) for binding glucose of at least 350 M −1 .

9 . The hydrogel of claim 1 , wherein

has an equilibrium constant (K eq ) for binding glucose of at least 1000 M −1 .

10 . The hydrogel of claim 1 , wherein

has an equilibrium constant (K eq ) for binding glucose that is at least 20 times greater than equilibrium constant of

for binding lactate.

11 . The hydrogel of claim 1 , wherein

comprises:

12 . The hydrogel of claim 1 , wherein

comprises a polyethylene glycol.

13 . The hydrogel of claim 12 , wherein the diboronate compound of formula (I) comprises:

wherein n is 2 to 250.

14 . The hydrogel of claim 1 , wherein

comprises a polyamidoamine dendrimer.

15 . The hydrogel of claim 1 , wherein

comprises hyaluronic acid.

16 . The hydrogel of claim 1 , wherein the molar ratio of the diboronate compound of formula (I) to the diol compound of formula (II) is 1:1.

17 . The hydrogel of claim 1 , wherein

comprises polyethylene glycol.

18 . The hydrogel of claim 17 , wherein the diol compound of formula (II) comprises:

wherein n is 2 to 250.

19 . The hydrogel of claim 1 , wherein

comprises a polyamidoamine dendrimer.

20 . A pharmaceutical composition comprising insulin encapsulated within the hydrogel of claim 1 .

21 . A method of delivering insulin to a subject in need thereof, the method comprising: administering a pharmaceutical composition to a subject in need thereof, the pharmaceutical composition comprising insulin encapsulated within a hydrogel, the hydrogel comprising:

(i) a diboronate compound of formula (I):

wherein:

 wherein:

R 1 , at each occurrence, is independently C 1-4 alkyl, cyclopropyl, C 1-2 fluoroalkyl, —F, —CN, or —NO 2 ;

R 2 , at each occurrence, is independently C 1-4 alkyl, cyclopropyl, C 1-2 fluoroalkyl, —F, —CN, or —NO 2 ; and

X ⊖ is an anion having a net charge of −1;

 is a linking moiety; and

 is a first moiety comprising a hydrophilic polymer, a hyperbranched macromolecule, or a combination thereof; and

(ii) a diol compound of formula (II):

wherein:

 is a second moiety comprising a hydrophilic polymer, a hyperbranched macromolecule, or a combination thereof;

wherein the diboronate compound of formula (I) and the diol compound of formula (II) form crosslinks by dynamic-covalent bonds.

Assignments (1)

Continuity (2)

References Cited (359)