Oxygen reactive polymers for treatment of traumatic brain injury

Patent metadata

Field	Value
Publication number	US-12329773-B2
Application number	US-202117379401-A
Country	US
Kind code	B2
Filing date	Jul 19, 2021
Priority date	Oct 6, 2015
Publication date	Jun 17, 2025
Grant date	Jun 17, 2025

Abstract

Methods and compositions for treating traumatic brain injury. The methods and compositions utilize a multi-functional oxygen reactive polymer (ORP) that includes repeating units that include a reactive oxygen species (ROS) scavenging group and a polyalkylene oxide group. For theranostic applications, the oxygen reactive polymer further includes a diagnostic group.

First claim

The invention claimed is:

1. A method for treating traumatic brain injury, comprising administering a therapeutically effective amount of a copolymer to a subject in need thereof, wherein the copolymer has the formula

wherein
n is an integer from 1 to 12,
m is an integer from 0 to 12,
p is an integer from 6 to 40,
R 1 and R 2 are independently selected from hydrogen or methyl,
a is the mole fraction of the repeating unit and is from about 0.25 to about 0.95,
b is the mole fraction of the polyalkylene oxide containing repeating unit and is from about 0.05 to about 0.75;
a+b is 1.0; and
* represents the remainder of the copolymer.

2. The method of claim 1 , wherein treating traumatic brain injury comprises reducing neurodegeneration.

3. The method of claim 1 , wherein treating traumatic brain injury comprises altering gliosis.

4. The method of claim 1 , wherein treating traumatic brain injury comprises treating the secondary effects of traumatic brain injury.

5. The method of claim 1 , wherein treating traumatic brain injury comprises treating one or more of reperfusion injury, delayed cortical edema, blood-brain barrier breakdown, local electrolyte imbalance, neurovascular unit dysfunction, and intracranial pressure.

6. The method of claim 1 , wherein administering the copolymer comprises intravenous, intranasal, intrathecal/intraventrical, or intracranial administration.

7. The method of claim 1 , wherein the copolymer is in the form of a nanoparticle.

8. The method of claim 1 , wherein the copolymer is a random copolymer.

9. The method of claim 1 , wherein the polymer further comprises a diagnostic group.

10. The method of claim 9 , wherein the diagnostic group is a magnetic resonance imaging group, a radiolabel group, a fluorescent group, a luminescent group, an X-ray/CT group, or an ultrasound group.

11. The method of claim 1 , wherein the polymer has a hydrodynamic diameter from about 4 to about 100 nm.

12. The method of claim 1 , wherein the polymer has a molar mass dispersity from about 1.05 to about 1.30.

13. The method of claim 1 , wherein the polymer has a number average molecular weight (M n ) from about 5,000 to about 100,000.

14. A copolymer having the formula

wherein
n is an integer from 1 to 12,
m is an integer from 0 to 12,
p is an integer from 6 to 40,
R 1 and R 2 are independently selected from hydrogen or methyl,
a is the mole fraction of the repeating unit and is from about 0.25 to about 0.95,
b is the mole fraction of the repeating unit and is from about 0.05 to about 0.75;
a+b is 1.0; and
* represents the remainder of the copolymer.

15. The copolymer of claim 14 in the form of a nanoparticle.

16. The copolymer of claim 14 , wherein the copolymer is a random copolymer.

Assignees

• Univ Washington

Inventors

• Stayton Patrick S
• Ypma Menko P
• Chiarelli Peter A
• Park Joshua Sang Hun
• Ellenbogen Richard G
• Xu Julia Mengyun
• Mourad Pierre D
• Lee Donghoon
• Convertine Anthony
• Kievit Forrest M

Classifications

• A61K31/795

  Polymers containing sulfur · CPC title

• A61K9/51

  Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)} · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K9/14

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title