# US 10,370,391 B2 · Hydrogen peroxide-activable, anti-oxidant compounds and methods using same

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- Number: US 10,370,391 B2
- Document ID: US10370391B2
- Status: Granted
- Kind: B2
- Application number: 15/583,517
- Filed: 2017-05-01
- Published: 2018-04-19
- Granted: 2019-08-06
- Earliest claimed: 2014-11-03
- Assignees: Beth Israel Deaconess Medical Center, Inc.; Chonbuk National University Industrial Cooperation Foundation
- Applicants: Beth Israel Deaconess Medical Center, Inc.; Chonbuk National University Industrial Cooperation Foundation
- Inventors: Peter M. Kang; Dongwon Lee; Seunggyu Park; Dahee Jeong
- Web page: https://patentgrep.com/patent/US10370391B2

## CPC

- C07F 5/025: {Boronic and borinic acid compounds}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 31/69: Boron compounds
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention includes 4-(hydroxymethyl)phenylboronic esters, which react with hydrogen peroxide to form 4-hydroxybenzyl alcohol, which is an anti-inflammatory and/or anti-oxidant compound, as well as microparticles and compositions thereof. In certain embodiments, the compositions of the invention may be used to treat or prevent oxidative stress and/or inflammation, including ischemic disease.

## Claims

### Claim 1

A method of reducing inflammation associated with ischemic reperfusion injury in a subject, the method comprising administering to the subject an effective amount of a microparticle comprising 4-(hydroxymethyl)phenylboronic ester, wherein the boronic ester comprises an alcohol selected from the group consisting of a diol, triol, tetraol, pentaol, hexaol and a higher polyol, wherein the alcohol and 4-(hydroxymethyl)phenylboronic acid are covalently conjugated to form the boronic ester, wherein the microparticle comprises a polymer or liposome, thereby reducing inflammation associated with ischemic reperfusion injury relative to a reference.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method reduces TNF-α and/or inducible nitric oxide synthase levels in the subject.

### Claim 3 (depends on 1)

The method of claim 1, wherein the ester is encapsulated in a poly(lactic-co-glycolic acid) (PLGA) microparticle.

### Claim 4 (depends on 1)

The method of claim 1, wherein the alcohol comprises 1,3-propanediol or 2-(hydroxymethyl)-2-methylpropane-1,3-diol.

### Claim 5 (depends on 1)

The method of claim 1, wherein the boronic ester comprises 4-(5-(hydroxymethyl)-5-methyl-1,3,2-dioxaborinan-2-yl)phenyl methanol or 4-(1,3,2-dioxaborinan-2-yl)phenyl methanol.

### Claim 6 (depends on 1)

The method of claim 1, wherein the polymer comprises at least one selected from the group consisting of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), and poly(ε-caprolactone) (PCL).

### Claim 7 (depends on 1)

The method of claim 1, wherein the reference is the level of inflammation present in an untreated control subject.

### Claim 8 (depends on 1)

The method of claim 1, wherein the inflammation is associated with acute coronary syndrome, hepatic ischemia, renal ischemia, brain ischemic injury, coronary artery disease, cardiopulmonary bypass surgery and/or a vascular thromboembolic event.