Claims for Patent: 11,850,221

Summary for Patent: 11,850,221

Title:	Ophthalmic pharmaceutical compositions and uses thereof
Abstract:	Provided herein are ophthalmic pharmaceutical compositions comprising (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide (WS-12) for effectively treating dry eye in a subject in need thereof, effectively reducing dry eye in a subject in need thereof, effectively reducing the likelihood of dry eye in a subject in need thereof, or for treating, preventing, or ameliorating signs or symptoms of dry eye in a subject in need thereof.
Inventor(s):	Anjali Joshi
Assignee:	Alcon Inc
Application Number:	US18/082,844
Patent Claims:	1. An ophthalmic pharmaceutical composition, comprising: about 0.0005% w/v to about 0.01% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide or a pharmaceutically acceptable salt thereof; about 0.1% w/v to about 5 w/v of a solubilizing agent selected from polyethylene glycol 400, castor oil, polyoxyethylene (20) sorbitan mono-oleate, or polyoxyl 35 castor oil; about 0.1% w/v to about 0.5% w/v of a viscosity modifier; a buffer; and about 0.1% w/v to about 1.0% w/v of a tonicity agent. 2. The ophthalmic pharmaceutical composition of claim 1, having a pH of about 5.0 to about 8.5. 3. The ophthalmic pharmaceutical composition of claim 1, having a pH of about 6.7 to about 7.3. 4. The ophthalmic pharmaceutical composition of claim 1, further comprising a pH adjuster. 5. The ophthalmic pharmaceutical composition of claim 4, wherein the pH adjuster is 1N sodium hydroxide and the pH is adjusted to about 7. 6. An ophthalmic pharmaceutical composition, consisting of: about 0.0005% w/v to about 0.01% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide or a pharmaceutically acceptable salt thereof; about 0.1% w/v to about 5 w/v of a solubilizing agent selected from polyethylene glycol 400, castor oil, polyoxyethylene (20) sorbitan mono-oleate, or polyoxyl 35 castor oil; about 0.1% w/v to about 0.5% w/v of a viscosity modifier; a buffer; about 0.1% w/v to about 1.0% w/v of a tonicity agent; water; and a pH of about 5.0 to about 8.5. 7. The ophthalmic pharmaceutical composition of claim 1, wherein the solubilizing agent is polyoxyl 35 castor oil. 8. The ophthalmic pharmaceutical composition of claim 1, wherein the viscosity modifier is selected from a cellulose derivative, a clay, a natural gum, a synthetic polymer, colloidal silicon dioxide, or any combination thereof. 9. The ophthalmic pharmaceutical composition of claim 8, wherein: the cellulose derivative is selected from methylcellulose, microcrystalline cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, or hydroxypropyl methylcellulose; the clay is selected from hectorite, bentonite, aluminum silicate, magnesium silicate, kaolin, or a combination thereof; and the natural gum is selected from acacia, guar gum, tragacanth, xanthan gum, alginate, carrageenan, or locust bean gum. 10. The ophthalmic pharmaceutical composition of claim 1, wherein the viscosity modifier comprises hydroxypropyl methylcellulose. 11. The ophthalmic pharmaceutical composition of claim 1, wherein the tonicity agent is selected from dextrose, glycerin, mannitol, potassium chloride, or sodium chloride. 12. The ophthalmic pharmaceutical composition of claim 1, wherein the tonicity agent is sodium chloride. 13. The ophthalmic pharmaceutical composition of claim 1, wherein the buffer is selected from a phosphate buffer, a citrate buffer, TRIS Base, TRIS HCl, PBS, HEPES, MES, PIPES, or TES. 14. The ophthalmic pharmaceutical composition of claim 1, wherein the buffer is a phosphate buffer. 15. The ophthalmic pharmaceutical composition of claim 1, further comprising purified water. 16. The ophthalmic pharmaceutical composition of claim 1, comprising: about 0.003% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 17. The ophthalmic pharmaceutical composition of claim 1, comprising: about 0.0014% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH in order to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 18. The ophthalmic pharmaceutical composition of claim 1, comprising: about 0.003% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7.0; and purified water q.s to about 1.0 mL. 19. The ophthalmic pharmaceutical composition of claim 1, comprising: about 0.0014% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7.0; and purified water q.s to about 1.0 mL. 20. A method of treating dry eye or reducing the likelihood of dry eye in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the ophthalmic pharmaceutical composition of claim 1. 21. A method of treating an ophthalmic disease or disorder that involves tear production or reducing the signs or symptoms of the ophthalmic disease or disorder that involves tear production in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the ophthalmic pharmaceutical composition of claim 1. 22. The method of claim 21, wherein the ophthalmic disease or disorder is dry eye. 23. A method of treating ocular irritation involving tear production or reducing ocular irritation involving tear production in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the ophthalmic pharmaceutical composition of claim 1. 24. The method of claim 20, wherein the ophthalmic pharmaceutical composition comprises: about 0.003% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 25. The method of claim 20, wherein the ophthalmic pharmaceutical composition comprises: about 0.0014% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 26. The method of claim 21, wherein the ophthalmic pharmaceutical composition comprises: about 0.003% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 27. The method of claim 21, wherein the ophthalmic pharmaceutical composition comprises: about 0.0014% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 28. The method of claim 26, wherein the ophthalmic disease or disorder is dry eye. 29. The method of claim 23, wherein the ophthalmic pharmaceutical composition comprises: about 0.003% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 30. The method of claim 23, wherein the ophthalmic pharmaceutical composition comprises: about 0.0014% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide; about 0.14% w/v hypromellose; about 3.0% w/v polyoxyl 35 castor oil; about 0.78% w/v sodium dihydrogen phosphate dihydrate buffer; about 0.55% w/v NaCl; a sufficient amount of NaOH to provide the ophthalmic pharmaceutical composition with a pH of about 7; and purified water. 31. The method of claim 20, wherein the ophthalmic pharmaceutical composition is administered topically to the subject. 32. The ophthalmic pharmaceutical composition of claim 1, wherein the ophthalmic pharmaceutical composition is stored in a polyolefin container.