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Methods for treating blood-brain barrier dysfunction and methods for treating recurrent seizures in a subject involve inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2).

Titel:	TREATMENTS FOR BLOOD-BRAIN BARRIER DYSFUNCTION AND RECURRENT SEIZURES USING NOX/LOX/COX INHIBITORS
Link:	Zum Volltext
Veröffentlichung:	2024
Medientyp:	Patent
Sonstiges:	Nachgewiesen in: USPTO Patent Applications Sprachen: English Document Number: 20240091240 Publication Date: March 21, 2024 Appl. No: 18/370558 Application Filed: September 20, 2023 Claim: 1. A method for treating blood-brain barrier (BBB) dysfunction in a subject, comprising: administering to the subject an effective amount of a combination of a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor and one or more inhibitors for inhibiting 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) to reduce BBB leakage. Claim: 2. The method of claim 1, wherein the NOX inhibitor is N-acetylcysteine. Claim: 3. The method of claim 1, wherein the one or more inhibitors for inhibiting 5-LOX and COX-2 comprises a 5-LOX inhibitor and a COX-2 inhibitor. Claim: 4. The method of claim 3, wherein the 5-LOX inhibitor is zileuton. Claim: 5. The method of claim 3, wherein the COX-2 inhibitor is celecoxib. Claim: 6. The method of claim 3, wherein the NOX inhibitor is N-acetylcysteine, the 5-LOX inhibitor is zileuton, and the COX-2 inhibitor is celecoxib. Claim: 7. The method of claim 6, wherein administering the effective amount of the combination comprises administering N-acetylcysteine in a dosage of about 100 mg/kg, administering zileuton in a dosage of about 5 mg/kg, and administering celecoxib in a dosage of about 10 mg/kg. Claim: 8. The method of claim 1, wherein the one or more inhibitors for inhibiting 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) comprises a dual 5-LOX/COX-2 inhibitor. Claim: 9. The method of claim 8, wherein the dual 5-LOX/COX-2 inhibitor is licofelone. Claim: 10. The method of claim 1, wherein the combination is administered to the subject in a single dosage form. Claim: 11. The method of claim 1, wherein the combination is administered in a multi-dosage form. Claim: 12. The method of claim 1, wherein the combination is administered to the subject twice daily for at least two days. Claim: 13. The method of claim 1, and further comprising: identifying the subject as having seizures, epilepsy, Alzheimer's disease and/or dementia, 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). Claim: 14. The method of claim 1, wherein reduced BBB leakage is characterized by a reduction in brain capillary leakage. Claim: 15. A method for treating recurrent seizures, comprising: administering a combination of a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor and one or more inhibitors for inhibiting 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) to a subject in need thereof. Claim: 16. The method of claim 15, and further comprising identifying the subject as having Alzheimer's disease with epilepsy. Claim: 17. The method of claim 15, wherein the NOX inhibitor is N-acetylcysteine. Claim: 18. The method of claim 15, wherein the one or more inhibitors for inhibiting 5-LOX and COX-2 comprises a 5-LOX inhibitor and a COX-2 inhibitor. Claim: 19. The method of claim 18, wherein the 5-LOX inhibitor is zileuton. Claim: 20. The method of claim 18, wherein the COX-2 inhibitor is celecoxib. Claim: 21. The method of claim 18, wherein the NOX inhibitor is N-acetylcysteine, the 5-LOX inhibitor is zileuton, and the COX-2 inhibitor is celecoxib. Claim: 22. The method of claim 21, wherein administering the combination comprises administering N-acetylcysteine in a dosage of about 100 mg/kg, administering zileuton in a dosage of about 5 mg/kg, and administering celecoxib in a dosage of about 10 mg/kg. Claim: 23. The method of claim 15, wherein the one or more inhibitors for inhibiting 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) comprises a dual 5-LOX/COX-2 inhibitor. Claim: 24. The method of claim 23, wherein the dual 5-LOX/COX-2 inhibitor is licofelone. Claim: 25. The method of claim 15, wherein the combination is administered to the subject in a single dosage form. Claim: 26. The method of claim 15, wherein the combination is administered in a multi-dosage form. Claim: 27. The method of claim 15, wherein the combination is administered to the subject twice daily for at least two days. Claim: 28. The method of claim 15, and further comprising administering an anti-seizure drug (ASD). Current International Class: 61; 61; 61; 61; 61

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TREATMENTS FOR BLOOD-BRAIN BARRIER DYSFUNCTION AND RECURRENT SEIZURES USING NOX/LOX/COX INHIBITORS