Nasal calcitonin formulations containing chlorobutanol
View Patent ↗An aqueous solution of calcitonin suitable for intranasal administration comprised of calcitonin, chlorobutanol at a concentration of less than 0.4% weight/weight, and water and having a pH of less than 4 with the proviso that benzalkonium chloride is not present in the solution. The aqueous solution of calcitonin can be used to treat osteoporosis, Paget's bone disease and hypercalcemia.
1. A method for intranasal administration of calcitonin which comprises administering intranasally to an individual a solution of calcitonin comprising calcitonin, only one preservative and a liquid diluent or carrier solution suitable for application to the nasal mucosa, wherein the preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight.
2. The method of claim 1 , wherein the calcitonin is selected from the group consisting of salmon, human, porcine and eel calcitonin.
3. The method of claim 1 , the solution further comprising sodium chloride at a concentration of about 0.85%, wherein the calcitonin is present in the solution at a concentration of about 0.0355 weight/weight and wherein the solution has a pH of less than 4 and oxygen at a content of less than about 5%.
4. The method of claim 1 , wherein the liquid diluent or carrier solution is aqueous saline.
5. The method of claim 1 , the solution further comprising an additional ingredient selected from the group consisting of a surfactant and a ciliary stimulant.
6. The method of claim 1 , wherein the solution is administered into a nose of an individual through an actuator tip as a spray, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.
7. The method of claim 6 , wherein the spray produces droplets, wherein less than 5% of the droplets are less than 10 microns in size.
8. The method of claim 6 , wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.
9. A method of inhibiting the growth of a fungus, comprising administering intranasally to an individual a solution of calcitonin comprising calcitonin, only one preservative and a liquid diluent carrier solution suitable for application to the nasal mucosa, wherein the preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight.
10. The method of claim 9 , wherein the fungus is Penicillium steckii.
11. The method of claim 9 , wherein the calcitonin is selected from the group consisting of salmon, human, porcine and eel calcitonin.
12. The method of claim 9 , the solution further comprising sodium chloride at a concentration of about 0.85%, wherein the calcitonin is present in the solution at a concentration of about 0.0355 weight/weight and wherein the solution has a pH of less than 4 and oxygen at a content of less than about 5%.
13. The method of claim 9 , wherein the liquid diluent or carrier solution is aqueous saline.
14. The method of claim 9 , the solution further comprising an additional ingredient selected from the group consisting of a surfactant and a ciliary stimulant.
15. The method of claim 9 , wherein the solution is administered into a nose of an individual through an actuator tip as a spray, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4when measured at a height of 3.0 cm from the actuator tip.
16. The method of claim 15 , wherein the spray produces droplets, wherein less than 5% of the droplets are less than 10 microns in size.
17. The method of claim 15 , wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.
18. A composition comprising calcitonin, only one preservative and a liquid diluent carrier solution suitable for application to the nasal mucosa, wherein the preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight.
19. The composition of claim 16 , the solution further comprising an additional ingredient selected from the group consisting of a surfactant and a ciliary stimulant.
20. A composition consisting essentially of calcitonin, only one preservative, a liquid diluent carrier solution suitable for application to the nasal mucosa and optionally hydrochloric acid, wherein the preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight and wherein the composition is suitable for intranasal administration in humans.
21. A composition consisting essentially of calcitonin, only one preservative, a liquid diluent carrier solution suitable for application to the nasal mucosa and optionally hydrochloric acid, wherein the preservative is chlorobutanol at a concentration equal to or greater than about 0.25% and less than about 0.4% weight/weight and wherein the composition has a pH of 4 or less and wherein the composition is suitable for intranasal administration in humans.
22. The composition according to one of claims 18 and 20 - 21 , wherein the liquid diluent or carrier solution is aqueous saline.
23. The composition according to one of claims 18 and 20 - 21 , wherein the calcitonin is selected from the group consisting of salmon, human, porcine and eel calcitonin.
24. A pharmaceutical device comprising a composition according to claim 18 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.
25. A pharmaceutical device comprising a composition according to claim 18 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.
26. A pharmaceutical device comprising a composition according to claim 18 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip, wherein less than 5% of the droplets in the spray are smaller than 10 microns in size.
27. A pharmaceutical device comprising a composition according to claim 20 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.
28. A pharmaceutical device comprising a composition according to claim 20 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.
29. A pharmaceutical device comprising a composition according to claim 20 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip, wherein less than 5% of the droplets in the spray are smaller than 10 microns in size.
30. A pharmaceutical device comprising a composition according to claim 21 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip.
31. A pharmaceutical device comprising a composition according to claim 21 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern major axis of about 31.2 mm and a minor axis of about 27.4 mm.
32. A pharmaceutical device comprising a composition according to claim 21 and an actuator to produce an aerosol spray of the composition, wherein the spray has a spray pattern ellipticity ratio of from about 1.0 to about 1.4 when measured at a height of 3.0 cm from the actuator tip, wherein less than 5% of the droplets in the spray are smaller than 10 microns in size.