IP Library Granted Patent US 10,695,288
Granted Patent B2
US 10,695,288 · App. 14/946,732 · Granted Jun 30, 2020

Reactive oxygen species (ROS)-responsive compositions and methods thereof

Inventors: Craig L. Duvall (Nashville, TN); John R. Martin (Nashville, TN); Kristin P. O'Grady (Nashville, TN); Christopher E. Nelson (Nashville, TN)
Assignee: Vanderbilt University
A61K9/0019A61K9/107A61K9/1641A61K31/121A61K31/4468
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Quick Facts
Patent No.
US 10,695,288
App. No.
14/946,732
Granted
Jun 30, 2020
Kind
B2
Abstract

A reactive oxygen species savaging emulsion; the emulsion comprising an injectable pharmaceutically acceptable composition and a polymeric poly(propylene sulfide) microsphere for targeted delivery to a site with elevated reactive oxygen species. In embodiments of the present invention, the microsphere is loaded with a biologically active agent.

Claims (36)

1. A reactive oxygen species scavenging emulsion, the emulsion comprising an injectable pharmaceutically acceptable composition and a polymeric microsphere for targeted delivery to a site with elevated reactive oxygen species;

wherein the polymer of the polymeric microsphere consists of poly(propylene sulfide); and

wherein the microsphere has a diameter of at least 0.5 μm.

2. The emulsion of claim 1 , wherein the microsphere is loaded with a biologically active agent.

3. The emulsion of claim 2 , wherein the biologically active agent is at least one of an enzyme, organic catalyst, antibiotic, antioxidant, anti-reactive oxygen species (ROS) agent, anti-inflammatory, protein, glycoprotein, peptide, polyamino acid, antibody, epitopes of antibodies, nucleic acid, steroidal molecule, antiviral, antirejection agent, immunosuppressant, cytokine, carbohydrate, pharmaceutical, cell, virus, single chain fragment, siRNA, miRNA against the p53/MAP kinase pathway, virus vector, prion, anti-proliferative agents, anti-migratory agents, biologically active polymers, and combinations thereof.

4. The emulsion of claim 2 , wherein the biologically active agent is curcumin.

5. The emulsion of claim 2 , wherein the biologically active agent is anti-reactive oxygen species (ROS) agents.

6. The emulsion of claim 2 , wherein the biologically active agent is superoxide dismutase mimetic 4-hydroxy-TEMPO benzoate.

7. The emulsion of claim 2 , wherein the biologically active agent is an NF-κB pathway inhibitor.

8. The emulsion of claim 7 , wherein the NF-κB pathway inhibitor is TPCA-1.

9. The emulsion of claim 2 , wherein the biologically active agent is hydrophobic.

10. The emulsion of claim 1 , wherein the emulsion comprises at least one of an antioxidant, buffer, bacteriostat, bacterial antibiotic, or a combination thereof.

11. The emulsion of claim 1 , wherein the microsphere is about 0.5 μm to about 1.5 μm in diameter.

12. The emulsion of claim 1 , wherein the microsphere is about 1 μm to about 5 μm in diameter.

13. A method of treating inflammation-related pathologies in a patient in need thereof, comprising:

administering an inflammation-reducing effective amount of an emulsion, the emulsion comprising an injectable pharmaceutically acceptable composition and a polymeric microsphere for targeted delivery to a site with elevated reactive oxygen species, wherein the polymer of the polymeric microsphere consists of poly(propylene sulfide);

wherein the microsphere has a diameter of at least 0.5 μm and

wherein the microsphere is loaded with a biologically active agent.

14. The method of claim 13 , further comprising, prior to the administration step, identifying an inflammation site in the patient, and locally injecting the emulsion at the inflammation site.

15. The method of claim 13 , wherein the biologically active agent is at least one of an enzyme, organic catalyst, antibiotic, antioxidant, anti-reactive oxygen species (ROS) agent, anti-inflammatory, protein, glycoprotein, peptide, polyamino acid, antibody, epitopes of antibodies, nucleic acid, steroidal molecule, antiviral, antirejection agent, immunosuppressant, cytokine, carbohydrate, pharmaceutical, cell, virus, single chain fragment, siRNA, miRNA against the p53/MAP kinase pathway, virus vector, prion, anti-proliferative agents, anti-migratory agents, biologically active polymers, and combinations thereof.

16. The method of claim 13 , wherein the biologically active agent is curcumin, TPCA-1, superoxide dismutase mimetic 4-hydroxy-TEMPO benzoate.

17. A method of locally delivering an anti-inflammatory agent to a subject in need thereof, comprising:

identifying a site of oxidative stress and/or identifying an inflammation site;

administering a reactive oxygen species (ROS) scavenging effective amount of the emulsion of claim 1 to the site to locally treat the inflammation;

wherein the microsphere is loaded with a biologically active agent.

18. The method of claim 17 , wherein the emulsion is loaded with curcumin.

19. A method of locally delivering an anti-peripheral artery disease agent to a subject in need thereof, comprising:

identifying an inflammation site;

administering a reactive oxygen species (ROS) scavenging effective amount of the emulsion of claim 1 to the site to locally treat peripheral artery disease;

wherein the microsphere is loaded with a biologically active agent.

20. The method of claim 19 , wherein the emulsion is loaded with curcumin.

21. A method of locally treating osteoarthritis to a subject in need thereof, comprising:

identifying an osteoarthritis site;

administering an effective cartilage damage reducing amount of the emulsion of claim 1 to the site to locally treat the osteoarthritis;

wherein the microsphere is loaded with a biologically active agent.

22. The method of claim 21 , wherein the emulsion is loaded with TPCA-1.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 5, 2016
From: VANDERBILT UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 040807/0028 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2016
From: DUVALL, CRAIG L; MARTIN, JOHN R; O'GRADY, KRISTIN P; NELSON, CHRISTOPHER E
To: VANDERBILT UNIVERSITY
Reel/Frame 038453/0438 →
Continuity (2)
Provisional Application 62081999 · Nov 19, 2014
Related Publication 20160175265A1 · Jun 23, 2016