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

Patent metadata

Field	Value
Publication number	US-2016175265-A1
Application number	US-201514946732-A
Country	US
Kind code	A1
Filing date	Nov 19, 2015
Priority date	Nov 19, 2014
Publication date	Jun 23, 2016
Grant date	—

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.

First claim

We claim:

1 . 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.

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 poly(propylene sulfide) microsphere for targeted delivery to a site with elevated reactive oxygen species.

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 microsphere is loaded with a biologically active agent.

16 . The method of claim 15 , 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.

17 . The method of claim 2 , wherein the biologically active agent is curcumin, TPCA-1, superoxide dismutase mimetic 4-hydroxy-TEMPO benzoate.

18 . 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.

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

20 . 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.

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

22 . 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.

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

Assignees

• Univ Vanderbilt

Inventors

• Duvall Craig L
• Martin John R
• O'Grady Kristin P
• Nelson Christopher E

Classifications

• A61K31/12 Primary

  Ketones · CPC title

• A61K31/381

  having five-membered rings · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K9/0019 Primary

  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

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title