US2023293775A1PendingUtilityA1

Bone-promoting thermoresponsive macromolecules

Assignee: UNIV NORTHWESTERNPriority: Dec 9, 2016Filed: Jan 24, 2023Published: Sep 21, 2023

Est. expiryDec 9, 2036(~10.4 yrs left)· nominal 20-yr term from priority

Inventors:Guillermo A. Ameer Simona Morochnik

A61K 31/33A61L 27/52A61L 27/54A61L 2400/06A61L 2430/02A61P 19/08A61K 9/0024A61K 9/06A61K 38/06A61K 33/06A61K 9/0019A61K 31/661A61K 39/385A61K 2039/6093

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References

Claims

Abstract

Provided herein are injectable, thermoresponsive hydrogels that are liquid at room temperature, provide a carrier material, and gel at body temperature to allow for controlled release. In particular, PPCN-based hydrogels are provided with therapeutic agents (e.g., drugs, ions, etc.) incorporated within or appended thereto, and methods of preparation and use thereof, for example, for the promotion of bone formation/repair and/or the treatment of bone diseases.

Claims

exact text as granted — not AI-modified

1 . A composition comprising a PPCN-based hydrogel comprising citric acid, poly(ethylene glycol), glycerol 1,3-diglycerolate diacrylate, and poly-(N-isopropylacrylamide) monomers and at least one bioactive agent incorporated therein and/or appended thereto. 
     
     
         2 . The composition of  claim 1 , wherein the bioactive agent is an additional monomer incorporated into the PPCN-based hydrogel backbone. 
     
     
         3 . The composition of  claim 2 , wherein the bioactive agent is β-glycerophosphate. 
     
     
         4 . The composition of  claim 1 , wherein the bioactive agent is a pendant group appended to a PPCN hydrogel. 
     
     
         5 . The composition of  claim 4 , wherein the pendant group is a small molecule. 
     
     
         6 . The composition of  claim 4 , wherein the pendant group is a peptide. 
     
     
         7 . The composition of  claim 6 , wherein the bioactive agent is a cyclic Arg-Gly-Asp (cRGD) peptide. 
     
     
         8 . The composition of  claim 1 , wherein the bioactive agent is an ionic crosslinking agent. 
     
     
         9 . The composition of  claim 8 , wherein the bioactive agent is Ca 2+ , Ba 2+ , or Sr 2+ . 
     
     
         10 - 13 . (canceled) 
     
     
         14 . A composition comprising a PPCN-based peptide-displaying hydrogel comprising citric acid, poly(ethylene glycol), glycerol 1,3-diglycerolate diacrylate, and poly-(N-isopropylacrylamide) monomers, and a peptide covalently conjugated to carboxy groups of the citric acid monomers. 
     
     
         15 . The composition of  claim 14 , wherein the peptide is covalently conjugated via carbodiimide chemistry to carboxy groups of the citric acid monomers. 
     
     
         16 . The composition of  claim 14 , wherein the peptide is cyclic Arg-Gly-Asp (cRGD). 
     
     
         17 . The composition of  claim 16 , wherein the cRGD is covalently conjugated to carboxy groups of PPCN. 
     
     
         18 . A composition comprising a PPCN-based hydrogel comprising citric acid, poly(ethylene glycol), glycerol 1,3-diglycerolate diacrylate, and poly-(N-isopropylacrylamide) monomers, and metal ion crosslinks. 
     
     
         19 . The composition of  claim 18 , comprising metal-ion-crosslinked PPCN. 
     
     
         20 . The composition of  claim 19 , prepared by incubating the PPCN in the presence of a salt of the metal ion. 
     
     
         21 . The composition of  claim 19 , wherein the metal ion is Ca 2+ , Ba 2+ , or Sr 2+ . 
     
     
         22 . A method of facilitating bone repair comprising administering a composition of  claim 1  to fractured or diseased bone site, and allowing the composition to gel. 
     
     
         23 . (canceled)

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