Materials and methods of using an inhibitor of plasminogen activation to treat anastomotic leak

Patent metadata

Field	Value
Publication number	US-12383579-B2
Application number	US-201917049793-A
Country	US
Kind code	B2
Filing date	Apr 23, 2019
Priority date	Apr 23, 2018
Publication date	Aug 12, 2025
Grant date	Aug 12, 2025

Abstract

Disclosed herein is the de novo synthesis of phosphorylated polyethylene glycol compounds with three defined ABA (hy-drophilic/-phobic/-philic) structures: ABA-PEG10k-Pi10, ABA-PEG16k-Pi14, and ABA-PEG20k-Pi20 and linear polymer PEG20k-Pi20 absent of hydrophobic block. The disclosure also provides materials and methods for treating or reducing the risk or likelihood of developing, anastomotic leak or other microbe-mediated disorders by administering a therapeutically effective amount of a plasminogen inhibitor such as tranexamic acid and/or a phosphate-loaded polymer.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a plasminogen inhibitor and a phosphate-loaded triblock copolymer, wherein the triblock copolymer comprises:
(a) a hydrophobic core; and
(b) at least two polyethylene glycol chains,
wherein
at least one of the said two polyethylene glycol chains is a phosphorylated polyethylene glycol comprising more than two phosphate groups, and
the dispersity (D) of the copolymer is less than or equal to 1.10.

2. The pharmaceutical composition of claim 1 wherein the phosphate-loaded triblock copolymer is a phosphorylated form of ABA-polyethylene glycol-polyglycidol (ABA-PEG-PGly) or ABA-polyethylene-glycol-polyethoxyethyl glycidyl ether (ABA-PEG-PEEGE).

3. The pharmaceutical composition of claim 1 wherein the phosphorylated polyethylene glycol is ABA-PEG20k-Pi20.

4. The pharmaceutical composition of claim 1 wherein the plasminogen inhibitor is tranexamic acid, F-aminocaproic acid, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, plasminogen activator inhibitor-3, or antiplasmin.

5. The composition of claim 4 wherein the antiplasmin is alpha-2-antiplasmin.

6. The composition of claim 4 wherein the plasminogen inhibitor is tranexamic acid.

7. A method of treating anastomotic leak comprising administering the composition of claim 1 .

8. A method of reducing the risk of acquiring anastomotic leak comprising administering the composition of claim 1 .

Assignees

• Univ Chicago
• Univ Rush Medical Center

Inventors

• Alverdy John C
• Zaborina Olga Y
• Jacobson Richard A

Classifications

• A61K38/57

  from animals; from humans {(A61K38/553, A61K38/556 take precedence)} · CPC title

• A61K31/197

  the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205) · CPC title

• A61K31/196

  the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title