Claims for Patent: 9,415,007

Summary for Patent: 9,415,007

Title:	Cyanocobalamin low viscosity aqueous formulations for intranasal delivery
Abstract:	A stable pharmaceutical mercury-free aqueous solution of cyanocobalamin comprised of cyanocobalamin and water wherein said solution of cyanocobalamin is suitable for intranasal administration, has a viscosity less than about 1000 cPs, and wherein said solution of cyanocobalamin has a bioavailability of cyanocobalamin when administered intranasally of at least about 7% relative to an intramuscular injection of cyanocobalamin with the proviso that the solution is essentially free of mercury and mercury-containing compounds. The present invention is also directed towards a method for elevating the vitamin B12 levels in the cerebral spinal fluid (CSF) comprising administering intranasally a sufficient amount of a mercury-free cyanocobalamin solution so as to increase the average ratio of vitamin B12 in the CSF to that in the blood serum (B12 CSF/B12 Serum.times.100) to at least about 1.1 comprising intranasally administering an aqueous solution of a cyanocobalamin, wherein said solution of cyanocobalamin has a bioavailability of at least 7% relative to an intramuscular injection of a cyanocobalamin.
Inventor(s):	Quay; Steven C. (Edmonds, WA), Aprile; Peter C. (East Northport, NY), Go; Zenaida O. (Clifton, NJ), Sileno; Anthony P. (Brookhaven Hamlet, NY)
Assignee:	PAR PHARMACEUTICAL, INC. (Woodcliff Lake, NJ)
Application Number:	14/485,228
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,415,007
Patent Claims:	1. A method for elevating a level of vitamin B12 in a subject having vitamin B12 deficiency associated with gastric surgery, comprising: administering an aqueous solution of cyanocobalamin to the subject having vitamin B12 deficiency associated with gastric surgery, wherein the aqueous solution of cyanocobalamin comprises: cyanocobalamin; water; a buffer selected from the group consisting of citric acid, sodium citrate, monopotassium phosphate, disodium phosphate, potassium biphthalate, sodium hydroxide, sodium acetate, acetic acid, and combinations thereof; optionally, a humectant selected from the group consisting of sorbitol, propylene glycol, and glycerin, and combinations thereof; and optionally, a preservative selected from the group consisting of benzyl alcohol, parabens thimerosal, chlorobutanol, benzethonium chloride, and benzalkonium chloride, and combinations thereof; wherein the aqueous solution of cyanocobalamin is suitable for intranasal administration, has a viscosity of less than about 1000 cPs, and a bioavailability of cyanocobalamin when administered intranasally of at least about 7% relative to an intramuscular injection of cyanocobalamin. 2. The method of claim 1, wherein the cyanocobalamin is at a concentration of about 0.5% by total weight of solution. 3. The method of claim 1, wherein the buffer comprises citric acid at a concentration of about 0.12% by total weight of solution and sodium citrate at a concentration of about 0.32% by total weight of solution. 4. The method of claim 3, wherein the pH of the aqueous solution of cyanocobalamin is about 4 to about 6. 5. The method of claim 4, wherein the aqueous solution of cyanocobalamin contains a humectant. 6. The method of claim 5, wherein the humectant is glycerin at a concentration of about 2.23% by total weight of solution. 7. The method of claim 1, wherein the aqueous solution of cyanocobalamin contains a preservative. 8. The method of claim 7, wherein the preservative comprises chlorobutanol or benzalkonium chloride, or combinations thereof. 9. The method of claim 8, wherein the preservative is benzalkonium chloride at a concentration of about 0.02% by total weight of solution. 10. The method of claim 1, wherein the aqueous solution of cyanocobalamin contains no mercury or mercury-containing compounds. 11. The method of claim 1, wherein the aqueous solution of cyanocobalamin comprises: cyanocobalamin at a concentration of about 0.5% by total weight of the solution, citric acid at a concentration of about 0.12% by total weight of the solution, sodium citrate at a concentration of about 0.32% by total weight of the solution, glycerin at a concentration of about 2.23% by total weight of the solution, benzalkonium chloride at concentration of about 0.02% by total weight of the solution, and water. 12. The method of claim 1, wherein the aqueous solution of cyanocobalamin comprises: cyanocobalamin at a concentration of about 0.5% by total weight of the solution, citric acid at a concentration of about 0.12% by total weight of the solution, sodium citrate at a concentration of about 0.32% by total weight of the solution, glycerin at a concentration of about 2.23% by total weight of the solution, and water. 13. A method of using a kit for elevating a level of vitamin B12 in a subject having vitamin B12 deficiency associated with gastric surgery, the kit comprising: an aqueous solution of cyanocobalamin in a container; and an actuator coupled to the container, the actuator comprising a tip for producing a spray of the aqueous solution of cyanocobalamin when the actuator is engaged; the method comprising, administering the spray from the tip to a nose of a subject having vitamin B12 deficiency associated with gastric surgery, wherein the aqueous solution of cyanocobalamin comprises: cyanocobalamin; water; a buffer selected from the group consisting of citric acid, sodium citrate, monopotassium phosphate, disodium phosphate, potassium biphthalate, sodium hydroxide, sodium acetate, acetic acid, and combinations thereof; optionally, a humectant selected from the group consisting of sorbitol, propylene glycol, and glycerin, and combinations thereof; and optionally, a preservative selected from the group consisting of benzyl alcohol, parabens thimerosal, chlorobutanol, benzethonium chloride, and benzalkonium chloride, and combinations thereof; wherein the aqueous solution of cyanocobalamin has a viscosity of less than about 1000 cPs and a bioavailability of cyanocobalamin when administered intranasally of at least about 7% relative to an intramuscular injection of cyanocobalamin. 14. The method of claim 13, wherein the spray has a spray pattern ellipticity ratio of about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip. 15. The method of claim 13, wherein the spray comprises droplets, and wherein less than about 5% of the droplets are less than about 10 .mu.m in size. 16. The method of claim 13, wherein the spray comprises droplets, and wherein less than about 50% of the droplets are less than about 26.9 .mu.m in size. 17. The method of claim 13, wherein the spray has a spray pattern major axis and minor axis of about 25 to about 40 mm each. 18. The method of claim 13, wherein the cyanocobalamin is at a concentration of about 0.5% by total weight of solution. 19. The method of claim 13, wherein the aqueous solution of cyanocobalamin comprises: cyanocobalamin at a concentration of about 0.5% by total weight of the solution, citric acid at a concentration of about 0.12% by total weight of the solution, sodium citrate at a concentration of about 0.32% by total weight of the solution, glycerin at a concentration of about 2.23% by total weight of the solution, benzalkonium chloride at concentration of about 0.02% by total weight of the solution, and water. 20. The method of claim 13, wherein the aqueous solution of cyanocobalamin comprises: cyanocobalamin at a concentration of about 0.5% by total weight of the solution, citric acid at a concentration of about 0.12% by total weight of the solution, sodium citrate at a concentration of about 0.32% by total weight of the solution, glycerin at a concentration of about 2.23% by total weight of the solution, and water.