# US 11,433,052 B2 · 5-LOX and COX-2 inhibition for treatment in connection with blood-brain barrier dysfunction

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- Number: US 11,433,052 B2
- Document ID: US11433052B2
- Status: Granted
- Kind: B2
- Application number: 16/870,625
- Filed: 2020-05-08
- Published: 2020-11-12
- Granted: 2022-09-06
- Earliest claimed: 2019-05-08
- Assignees: University of Kentucky Research Foundation
- Applicants: University of Kentucky Research Foundation
- Inventors: Bjoern Bauer; Anika Maria Sophie Hartz; Brent Scot Sokola
- Web page: https://patentgrep.com/patent/US11433052B2

## CPC

- A61K 31/415: 1,2-Diazoles
- A61K 31/22: of acyclic acids, e.g. pravastatin
- A61K 31/381: having five-membered rings
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/08: Antiepileptics; Anticonvulsants
- 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

Methods of reducing blood brain barrier dysfunction involve inhibiting 5-LOX and COX-2.

## Claims

### Claim 1

A method of reducing brain capillary leakage, comprising: identifying a subject having seizure, epilepsy, Alzheimer's disease and/or dementias, Parkinson's disease, brain cancer, multiple sclerosis, stroke, brain trauma, an infectious disease of the brain, and/or peripheral inflammation or inflammation of the central nervous system (CNS), and administering to the subject an effective amount of a composition to inhibit 5-LOX and COX-2 to reduce brain capillary leakage.

### Claim 2 (depends on 1)

The method of claim 1, wherein the composition comprises a 5-LOX inhibitor and a COX-2 inhibitor.

### Claim 3 (depends on 2)

The method of claim 2, wherein the 5-LOX inhibitor is zileuton.

### Claim 4 (depends on 2)

The method of claim 2, wherein the COX-2 inhibitor is celecoxib.

### Claim 5 (depends on 2)

The method of claim 2, wherein the 5-LOX inhibitor is zileuton and the COX-2 inhibitor is celecoxib.

### Claim 6 (depends on 1)

The method of claim 1, wherein the composition comprises a dual 5-LOX/COX-2 inhibitor.

### Claim 7 (depends on 6)

The method of claim 6, wherein the dual 5-LOX/COX-2 inhibitor is licofelone.

### Claim 8 (depends on 1)

The method of claim 1, and further including a lipoxin A4 receptor (LXA4-R) agonist.

### Claim 9 (depends on 8)

The method of claim 8, wherein the LXA4-R agonist is BLM-111 ((5R,6R)-methyl 5,6,7-trihydroxyheptanoate).

### Claim 10 (depends on 1)

The method of claim 1, and further comprising administering an anti-seizure drug (ASD).

### Claim 11

A method of reducing brain capillary leakage, for treating a subject for blood-brain barrier (BBB) dysfunction, comprising identifying the subject as having or being at risk of BBB dysfunction, and administering to the subject an effective amount of a composition to inhibit 5-LOX and COX-2.

### Claim 12 (depends on 11)

The method of claim 11, wherein the subject has or is at risk of having seizure, epilepsy, Alzheimer's disease and/or dementias, Parkinson's disease, brain cancer, multiple sclerosis, stroke, brain trauma, an infectious disease of the brain, or peripheral inflammation or inflammation of the central nervous system (CNS).

### Claim 13

A method of reducing brain capillary leakage, for treating a subject displaying epileptogenesis, comprising identifying the subject has displaying epileptogenesis, and administering to the subject the composition an effective amount of a composition to inhibit 5-LOX and COX-2.

### Claim 14 (depends on 13)

The method of claim 13, and further comprising identifying the subject as having a need for controlling seizures.

### Claim 15 (depends on 13)

The method of claim 13, wherein the epileptogenesis the subject displays epileptogenesis following brain trauma or a central nervous system (CNS) condition.

### Claim 16 (depends on 11, 13)

The method of claim 11 or 13, wherein the composition comprises a 5-LOX inhibitor and a COX-2 inhibitor.

### Claim 17 (depends on 16)

The method of claim 16, wherein the 5-LOX inhibitor is zileuton.

### Claim 18 (depends on 16)

The method of claim 16, wherein the COX-2 inhibitor is celecoxib.

### Claim 19 (depends on 16)

The method of claim 16, wherein the 5-LOX inhibitor is zileuton and the COX-2 inhibitor is celecoxib.

### Claim 20 (depends on 11, 13)

The method of claim 11 or 13, wherein the composition comprises a dual 5-LOX/COX-2 inhibitor.

### Claim 21 (depends on 20)

The method of claim 20, wherein the dual 5-LOX/COX-2 inhibitor is licofelone.

### Claim 22 (depends on 11, 13)

The method of claim 11 or 13, and further including a lipoxin A4 (LXA4) agonist.

### Claim 23 (depends on 22)

The composition of claim 22, wherein the LXA4 agonist is BLM-111 ((5R,6R)-methyl 5,6,7-trihydroxyheptanoate).

### Claim 24 (depends on 11, 13)

The method of claim 11 or 13, and further comprising administering an anti-seizure drug (ASD).