Patent EA-004307-B1 (EA)
Title: High potency dihydroergotamine compositions
Inventor: PLACHETKA JOHN R
IPC: A61P25/06
Filed: 2000-03-15
Abstract: 1. A method of making a therapeutic package comprising a) a pharmaceutical composition in unit dose form, comprising: dihydroergotamine (DHE) in an amount such that one or more unit doses of said composition are effective in the symptomatic treatment of migraine headache when administered to a patient; and a pharmaceutically acceptable liquid vehicle, in which said DHE is dissolved at a concentration of at least 2.9 mM, and b) infilled, injectable syringe containing said composition. 2. The pharmaceutical composition of claim 1 further comprising sufficient dissolved CO2 and/or N2 to retard the oxidative degradation of said composition. 3. The method of claim 1 further comprising an opaque, sealed package containing said syringe filled with said composition and from which oxygen has been excluded. 4. A therapeutic package produced by the process of either claim 2 or claim 3. 5. A method of making a therapeutic package comprising a) a pharmaceutical composition in unit dose form, comprising dihydroergotamine (DHE) in an amount such that one or more unit doses of said composition are effective in the symptomatic treatment of migraine headache when administered to a patient; and a pharmaceutically acceptable liquid vehicle, in which said DHE is dissolved at a concentration of at least 2.9 mM, and b) infilled, injectable syringe containing said composition. 6. The method of claim 5 further comprising an opaque, sealed package containing said syringe filled with said composition and from which oxygen has been excluded. 7. The pharmaceutical composition of claim 5 further comprising sufficient dissolved CO2 and/or N2 to retard the oxidative degradation of said composition. 8. A pharmaceutical composition in unit dose form, comprising: (a) dihydroergotamine (DHE) in an amount such that one or more unit doses of said composition are effective in the symptomatic treatment migraine headache when administered to a patient; (b) a pharmaceutically acceptable liquid vehicle, in which said DHE is dissolved at a concentration of at least 2.9 mM; and (c) caffeine at between a 0.1: 1 and 10: 1 weight ratio with DHE. 9. The pharmaceutical composition of claim 8, wherein said caffeine is in a 1: 1 weight ratio with said DHE. 10. The pharmaceutical composition of claim 8 further comprising sufficient dissolved CO2 and/or N2 to retard the oxidative degradation of said composition. 11. The pharmaceutical composition of claim 8 further comprising an antioxidant. 12. The pharmaceutical composition of claim 8, wherein said DHE is present as dihydroergotamine mesylate. 13. A method for the symptomatic treatment of a patient for migraine headache comprising administering to said patient one or more unit doses of the pharmaceutical composition of either of claims 8-12. 14. The method of claim 13, wherein said pharmaceutical composition is administered by subcutaneous injection. 15. The method of claim 13, wherein said patient is treated with a total dosage of between 0.5 mg and 5.0 mg per migraine attack. 16. A process for preparing a therapeutic package comprising: (a) preparing a unit dose of pharmaceutical composition according to any of claims 8-12; and (b) infilling of an injectable syringe with said pharmaceutical composition. 17. The process of claim 16 further comprising enclosing the syringe infilled with said pharmaceutical composition in an opaque, sealed package from which oxygen has been excluded. 18. A therapeutic package produced by the process of claim 16. 19. A therapeutic package comprising: (a) a unit dose of pharmaceutical composition according to any of claims 8-12; and (b) infilled injectable syringe with said pharmaceutical composition. 20. The process of claim 16 further comprising enclosing the syringe infilled with said pharmaceutical composition in an opaque, sealed package from which oxygen has been excluded. 21. The improvement of a unit dose of pharmaceutical composition containing a DHE solution and indicated for use in treatment of migraine headache, which comprises: (a) a concentration of DHE in said composition of at least 2 mg/ml; (b) carbon dioxide and/or nitrogen dissolved in said composition at a concentration sufficient to retard oxidative degradation of said composition; and (c) caffeine at between a 0.1:1 and 10: 1 weight ratio with DHE. 22. The improvement of a method for the symptomatic treatment of a patient suffering from or susceptible to the development of a migraine attack including the use of a pharmaceutical composition of DHE, which comprises administering one or more unit doses of the composition according to any one of claims 8-12.