Claims for Patent: RE43580

Summary for Patent: RE43580

Title:	Nasal calcitonin formulations
Abstract:	.[.A liquid pharmaceutical composition is disclosed comprising calcitonin or an acid addition salt thereof and citric acid or salt thereof in a concentration from about to about 50 mM, said composition being in a form table for nasal administration..]. .Iadd.A liquid pharmaceutical composition is provided for nasal administration of calcitonin or an acid addition salt thereof. The nasal pharmaceutical formulations contain a component selected from the group consisting of citric acid, citric acid salt and a combination thereof. .Iaddend.
Inventor(s):	Stern; William (Tenafly, NJ)
Assignee:	Unigene Laboratories, Inc. (Boonton, NJ)
Application Number:	12/459,385
Patent Claims:	1. A liquid pharmaceutical composition comprising calcitonin or an acid addition salt thereof and citric acid and/or salt thereof in a concentration from 10 to about 50 mM, said composition being in a form suitable for nasal administration..]. .[.2. The liquid pharmaceutical composition of claim 1 further comprising a pharmaceutically acceptable, aqueous liquid nasal carrier..]. .[.3. The liquid pharmaceutical composition of claim 2, wherein said carrier comprises aqueous saline..]. .[.4. The liquid pharmaceutical composition of claim 1, wherein said composition is in the form of a nasal spray..]. .[.5. The liquid pharmaceutical composition of claim 4 having a viscosity of less than 0.98 cP..]. .[.6. The liquid pharmaceutical composition of claim 1, wherein the calcitonin is selected from the group consisting of salmon calcitonin, human calcitonin, porcine calcitonin and 1,7-Asu-eel calcitonin..]. .[.7. The liquid pharmaceutical composition of claim 1, wherein the calcitonin is salmon calcitonin..]. .[.8. The liquid pharmaceutical composition of claim 1, wherein said calcitonin, or salt is present in an amount of from about 100 to about 8,000 MRC units/ml..]. .[.9. The liquid pharmaceutical composition of claim 1, wherein said calcitonin, or salt is present in an amount of from about 500 to about 4,000 MRC units/ml..]. .[.10. The liquid pharmaceutical composition of claim 1, wherein said calcitonin, or salt is present in an amount of from about 500 to about 3,000 MRC units/ml..]. .[.11. The liquid pharmaceutical composition of claim 1, wherein said calcitonin, or salt is present in an amount of from about 1,000 to about 2,500 MRC units/ml..]. .[.12. The liquid pharmaceutical composition of claim 1 having a pH of from about 3 to about 5. .]. .[.13. The liquid pharmaceutical composition of claim 1 having a pH of from about 3.5 to about 3.9..]. .[.14. The liquid pharmaceutical composition of claim 1 having a pH of about 3.7..]. 15. .[.The liquid pharmaceutical composition of claim 1.]. .Iadd.A liquid pharmaceutical composition comprising calcitonin or an acid addition salt thereof and a bioavailability enhancing agent selected from the group consisting of citric acid, citric acid salt and a combination thereof, wherein the combined concentration of all bioavailability enhancing agents is 10-25 mM, said composition being in a form suitable for nasal administration and .Iaddend.having an osmotic pressure of from .[.about.]. 250 to .[.about.]. 350 mOsm/liter.Iadd., wherein said citric acid or citric acid salt concentration is 20 mM, and wherein the pH of the composition is from 3.5 to 3.9.Iaddend.. .[.16. The liquid pharmaceutical composition of claim 1 further containing at least 0.1% by weight of polyoxyethylene(20) sorbitan monooleate..]. .[.17. The liquid pharmaceutical composition of claim 1 further containing at least one preservative selected from the group consisting of benzyl alcohol, phenylethyl alcohol, methyl parabens, ethyl parabens, propyl parabens and butyl parabens..]. .[.18. A liquid pharmaceutical composition comprising about 2,200 MRC units of salmon calcitonin, about 10 mM citric acid, about 0.2% phenylethyl alcohol, about 0.5% benzyl alcohol, and about 0.1% polyoxyethylene(20) sorbitan monooleate..]. .[.19. A liquid pharmaceutical composition comprising about 2,200 MIC units of salmon calcitonin, about 20 mM citric acid, about 0.2% phenylethyl alcohol, about 0.5% benzyl alcohol, and about 0.1% polyoxyethylene(20) sorbitan monooleate..]. 20. A method of administering a calcitonin to a subject requiring calcitonin treatment, which method comprises administering to said subject .[.a composition as defined in claim 1.]. via the nasal route .Iadd.a liquid pharmaceutical composition for nasal administration comprising calcitonin or an acid addition salt thereof and a bioavailability enhancing agent selected from the group consisting of citric acid, citric acid salt and a combination thereof, wherein the combined concentration of all bioavailability enhancing agents is 10-25 mM, said composition having a pH of from 3.5-3.9.Iaddend.. 21. The method of claim 20, wherein the amount of calcitonin administered is from about 200 to about 600 MRC units. .[.22. A method of improving the stability of a liquid pharmaceutical composition of calcitonin comprising adding citric acid or a salt thereof in a concentration from 10 to about 50 mM to said composition..]. .[.23. A method of improving the bioavailability or the concentration of plasma calcitonin in a subject following nasal administration of a liquid pharmaceutical composition of calcitonin, which method comprises adding citric acid or a salt thereof in a concentration from 10 to about 50 mM to said composition prior to said administration..]. .Iadd.24. The pharmaceutical composition of claim 15, wherein said composition includes aqueous saline. .Iaddend. .Iadd.25. The pharmaceutical composition of claim 15, wherein said composition has a viscosity of less than 0.98 cP..Iaddend. .Iadd.26. The pharmaceutical composition of claim 15, wherein said composition further contains at least 0.1% by weight of polyoxyethylene(20) sorbitan monooleate..Iaddend. .Iadd.27. The pharmaceutical composition of claim 15, wherein said composition further contains at least one preservative selected from the group consisting of benzyl alcohol, phenylethyl alcohol, methyl parabens, ethyl parabens, propyl parabens and butyl parabens..Iaddend. .Iadd.28. The pharmaceutical composition of claim 15, wherein said calcitonin is salmon calcitonin..Iaddend. .Iadd.29. A method of administering a calcitonin to a subject requiring calcitonin treatment, said method comprising nasally administering to said subject a therapeutically effective amount of the composition of claim 15..Iaddend. .Iadd.30. The method of claim 20 wherein the calcitonin is salmon calcitonin..Iaddend. .Iadd.31. An aqueous pharmaceutical composition for nasal delivery comprising salmon calcitonin or an acid addition salt thereof, a bioavailability enhancing agent selected from the group consisting of citric acid, citric acid salt and a combination thereof, wherein the combined concentration of all said bioavailability enhancing agents is 10-50 mM, said composition having a pH of from 3.5-3.9, and an osmotic pressure from 250 to 350 mOsm/liter..Iaddend. .Iadd.32. The pharmaceutical composition of claim 31, further containing at least one preservative selected from the group consisting of benzyl alcohol, phenylethyl alcohol, methyl parabens, ethyl parabens, propyl parabens and butyl parabens..Iaddend. .Iadd.33. The pharmaceutical composition of claim 31, wherein combined concentration of all said bioavailability enhancing agents is 20 mM..Iaddend. .Iadd.34. The pharmaceutical composition of claim 33, further comprising 0.2% phenylethyl alcohol, 0.5% benzyl alcohol and 0.1% polyoxyethylene (20) sorbitan monooleate..Iaddend. .Iadd.35. A method of administering a calcitonin to a subject requiring calcitonin treatment, said method comprising nasally administering to said subject a therapeutically effective amount of the composition of claim 31..Iaddend. .Iadd.36. A method of administering a calcitonin to a subject requiring calcitonin treatment, said method comprising nasally administering to said subject a therapeutically effective amount of the composition of claim 34..Iaddend.