Claims for Patent: 10,799,481

Summary for Patent: 10,799,481

Title:	Compositions and methods for treating ocular disorders
Abstract:	The present disclosure is directed to compositions comprising oxymetazoline and methods of treating various eye disorders related to drooping eyelids, such as ptosis, in a subject comprising administering to the subject compositions comprising oxymetazoline.
Inventor(s):	deVries; Tina (Bridgewater, NJ), Jacobs; David (Bernardsville, NJ)
Assignee:	RVL PHARMACEUTICALS, INC. (Bridgewater, NJ)
Application Number:	16/716,014
Patent Claims:	1. A method of treating ptosis in a subject, comprising administering to at least one eye of the subject a therapeutically effective amount of an aqueous pharmaceutically stable ophthalmic preservative-free formulation comprising: a) about 0.1 wt % oxymetazoline hydrochloride; b) about 0.64 wt % sodium chloride; c) about 0.075 wt % potassium chloride; d) about 0.048 wt % calcium chloride dihydrate; e) about 0.03 wt % magnesium chloride hexahydrate; f) about 0.39 wt % sodium acetate trihydrate and about 0.17 wt % sodium citrate; and g) about 0.5 wt % hypromellose; h) wherein the aqueous pharmaceutically stable ophthalmic formulation has a pH range from about 5.8 to about 6.8, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of from about 15 cPs to about 35 cPs and wherein the formulation is stable at 25.degree. C. and 40% relative humidity for a period of at least 24 months. 2. The method of claim 1, wherein the ptosis is acquired blepharoptosis. 3. The method of claim 1, wherein the formulation is administered to the subject on one or more consecutive days at a dose of one drop in each eye for a total daily dose of about 0.07 mg oxymetazoline hydrochloride. 4. The method of claim 3, wherein a mean C.sub.max after a single-dose administration of the formulation is between about 25 and about 35 pg/ml. 5. The method of claim 3, wherein a mean AUC.sub.0-.infin. after a single-dose administration of the formulation is between about 300 and about 700 pgh/mL. 6. The method of claim 3, wherein a T.sub.max after a single-dose administration of the formulation is between about 0.5 and about 6 hours. 7. A method of increasing the vertical separation of the upper eyelid and lower eyelid of at least one eye in a subject, comprising administering to at least one eye of the subject an aqueous pharmaceutically stable ophthalmic preservative-free formulation comprising: a) about 0.1 wt % oxymetazoline hydrochloride; b) about 0.64 wt % sodium chloride; c) about 0.075 wt % potassium chloride; d) about 0.048 wt % calcium chloride dihydrate; e) about 0.03 wt % magnesium chloride hexahydrate; f) about 0.39 wt % sodium acetate trihydrate and about 0.17 wt % sodium citrate; and g) about 0.5 wt % hypromellose; h) wherein the aqueous pharmaceutically stable ophthalmic formulation has a pH range from about 5.8 to about 6.8, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of from about 15 cPs to about 35 cPs and wherein the formulation is stable at 25.degree. C. and 40% relative humidity for a period of at least 24 months. 8. The method of claim 7, wherein the formulation is administered to the subject on one or more consecutive days at a dose of one drop in a single eye for a total daily dose of about 0.035 mg oxymetazoline hydrochloride. 9. The method of claim 7, wherein the formulation is administered to the subject on one or more consecutive days at a dose of one drop in each eye for a total daily dose of about 0.07 mg oxymetazoline hydrochloride. 10. The method of claim 9, wherein a mean C.sub.max after a single-dose administration of the formulation is between about 25 and about 35 pg/ml. 11. The method of claim 9, wherein a mean AUC.sub.0-.infin. after a single-dose administration of the formulation is between about 300 and about 700 pgh/mL. 12. The method of claim 9, wherein a T.sub.max after a single-dose administration of the formulation is between about 0.5 and about 6 hours. 13. A method of improving a Leicester Peripheral Field Test (LPFT) score in a subject, comprising administering to at least one eye of the subject an aqueous pharmaceutically stable ophthalmic preservative-free formulation comprising: a) about 0.1 wt % oxymetazoline hydrochloride; b) about 0.64 wt % sodium chloride; c) about 0.075 wt % potassium chloride; d) about 0.048 wt % calcium chloride dihydrate; e) about 0.03 wt % magnesium chloride hexahydrate; f) about 0.39 wt % sodium acetate trihydrate and about 0.17 wt % sodium citrate; and g) about 0.5 wt % hypromellose; h) wherein the aqueous pharmaceutically stable ophthalmic formulation has a pH range from about 5.8 to about 6.8, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of from about 15 cPs to about 35 cPs, wherein the formulation is stable at 25.degree. C. and 40% relative humidity for a period of at least 24 months and whereby the mean LPFT score is increased by about 5-10 points after about 0.1-16 hours after administration. 14. The method of claim 13, wherein the formulation is administered to the subject on one or more consecutive days at a dose of one drop in each eye for a total daily dose of about 0.07 mg oxymetazoline hydrochloride. 15. The method of claim 14, wherein a mean C.sub.max after a single-dose administration of the formulation is between about 25 and about 35 pg/ml. 16. The method of claim 14, wherein a mean AUC.sub.0-.infin. after a single-dose administration of the formulation is between about 300 and about 700 pgh/mL. 17. The method of claim 14, wherein a T.sub.max after a single-dose administration of the formulation is between about 0.5 and about 6 hours. 18. The method of claim 13, wherein the Leicester Peripheral Field Test (LPFT) median score is increased by about 5-10 points after about 6 hours after administration. 19. The method of claim 13, wherein tachyphylaxis is not exhibited for at least six weeks. 20. A method of improving a Marginal Reflex Distance Test 1 (MRD-1) score in a subject, comprising administering to at least one eye of the subject an aqueous pharmaceutically stable ophthalmic preservative-free formulation comprising: a) about 0.1 wt % oxymetazoline hydrochloride; b) about 0.64 wt % sodium chloride; c) about 0.075 wt % potassium chloride; d) about 0.048 wt % calcium chloride dihydrate; e) about 0.03 wt % magnesium chloride hexahydrate; f) about 0.39 wt % sodium acetate trihydrate and about 0.17 wt % sodium citrate; and g) about 0.5 wt % hypromellose; h) wherein the aqueous pharmaceutically stable ophthalmic formulation has a pH range from about 5.8 to about 6.8, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of from about 15 cPs to about 35 cPs, wherein the formulation is stable at 25.degree. C. and 40% relative humidity for a period of at least 24 months and whereby the mean score is increased by about 0.2-1.5 points after about 1-20 minutes after administration or after about 0.1-16 hours after administration. 21. The method of claim 20, wherein the aqueous pharmaceutically stable ophthalmic formulation is administered to the subject on one or more consecutive days at a dose of one drop in each eye for a total daily dose of about 0.07 mg oxymetazoline hydrochloride. 22. The method of claim 21, wherein a mean C.sub.max after a single-dose administration of the formulation is between about 25 and about 35 pg/ml. 23. The method of claim 21, wherein a mean AUC.sub.0-.infin. after a single-dose administration of the formulation is between about 300 and about 700 pgh/mL. 24. The method of claim 21, wherein a T.sub.max after a single-dose administration of the formulation is between about 0.5 and about 6 hours. 25. The method of claim 20, wherein the Marginal Reflex Distance Test 1 (MRD-1) mean score is increased by about 0.2-1.0 points after about 5 minutes after administration. 26. The method of claim 20, wherein tachyphylaxis is not exhibited for at least six weeks. 27. The method of claim 1, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of about 25 cps. 28. The method of claim 7, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of about 25 cps. 29. The method of claim 13, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of about 25 cps. 30. The method of claim 20, wherein the aqueous pharmaceutically stable ophthalmic formulation has a viscosity of about 25 cps.