Salts of 2-amino-1-hydroxyethyl-8-hydroxyquinolin-2(1H)-one derivatives having both β2 adrenergic receptor agonist and M3 muscarinic receptor antagonist activities
US-9562039-B2 · Feb 7, 2017 · US
US12128013B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-12128013-B2 |
| Application number | US-202318236795-A |
| Country | US |
| Kind code | B2 |
| Filing date | Aug 22, 2023 |
| Priority date | Jan 23, 2013 |
| Publication date | Oct 29, 2024 |
| Grant date | Oct 29, 2024 |
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The present invention provides for the treatment, prevention, and/or reduction of a risk of a disease, disorder, or condition in which aldehyde toxicity is implicated in the pathogenesis, including ocular disorders, skin disorders, conditions associated with injurious effects from blister agents, and autoimmune, inflammatory, neurological and cardiovascular diseases by the use of a primary amine to scavenge toxic aldehydes, such as MDA and HNE.
Opening claim text (preview).
We claim: 1. A method of treating ocular rosacea with or without meibomian gland dysfunction, comprising administering to a subject with ocular rosacea with or without meibomian gland dysfunction, a therapeutically effective amount of a compound, wherein the compound is: or a pharmaceutically acceptable salt thereof. 2. The method of claim 1 , wherein the ocular rosacea is associated with high aldehyde levels as a result of inflammation. 3. The method of claim 1 , wherein the ocular rosacea is with a meibomian gland dysfunction. 4. The method of claim 1 , wherein the ocular rosacea is without a meibomian gland dysfunction. 5. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered systemically. 6. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered intraocularly. 7. The method of claim 6 , wherein the compound is: 8. The method of claim 3 , wherein the compound or pharmaceutically acceptable salt thereof is administered intraocularly. 9. The method of claim 4 , wherein the compound or pharmaceutically acceptable salt thereof is administered intraocularly. 10. The method of claim 1 , wherein the compound is administered topically to one or both eyes of the subject as an aqueous composition comprising the compound, and a cyclodextrin or a pharmaceutically acceptable salt thereof. 11. The method of claim 10 , wherein the cyclodextrin is a β-cyclodextrin or a pharmaceutically acceptable salt thereof selected from sulfobutylether-β-cyclodextrin, hydroxypropyl-ß-cyclodextrin, or a pharmaceutically acceptable salt thereof. 12. The method of claim 11 , wherein the β-cyclodextrin is hydroxypropyl-β-cyclodextrin, or a pharmaceutically acceptable salt thereof. 13. The method of claim 12 , wherein the hydroxypropyl-β-cyclodextrin is 2-hydroxypropyl-β-cyclodextrin, 3-hydroxypropyl-β-cyclodextrin, or a pharmaceutically acceptable salt thereof. 14. The method of claim 11 , wherein the β-cyclodextrin is sulfobutylether-β-cyclodextrin, or a pharmaceutically acceptable salt thereof. 15. The method of claim 14 , wherein the sulfobutylether-β-cyclodextrin is present at a concentration of about 0.01%-30% w/v. 16. The method of claim 15 , wherein the sulfobutylether-β-cyclodextrin is present at a concentration of about 5%-25% w/v. 17. The method of claim 10 , wherein the compound is present at a concentration of 0.08%-1.0% w/v; and the cyclodextrin is sulfobutylether-β-cyclodextrin, wherein the sulfobutylether-β-cyclodextrin is present at 6%-12% w/v. 18. The method of claim 17 , wherein the compound is present at a concentration of about 0.09%-0.5% w/v. 19. The method of claim 17 , wherein the compound is present at a concentration of about 0.1% w/v. 20. The method of claim 18 , wherein the sulfobutylether-β-cyclodextrin is present at a concentration of about 9.5% w/v.
with aromatically bound amino groups · CPC title
Quinones · CPC title
Oxygen-containing compounds {(C08K5/0091 takes precedence)} · CPC title
having six-membered rings with one nitrogen as the only ring hetero atom · CPC title
The ring being spiro-condensed with carbocyclic or heterocyclic ring systems · CPC title
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