Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Reexamination Certificate
2002-05-22
2004-10-19
Hartley, Michael G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
C424S046000, C514S414000, C514S220000, C514S620000, C514S323000, C128S200140, C128S200240, C128S203150
Reexamination Certificate
active
06805854
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the delivery of anti-migraine compounds through an inhalation route. Specifically, it relates to aerosols containing sumatriptan, frovatriptan, or naratriptan that are used in inhalation therapy.
BACKGROUND OF THE INVENTION
There are a number of compositions currently marketed for the treatment of migraine headaches. The compositions contain at least one active ingredient that provides for observed therapeutic effects. Among the active ingredients given in such anti-migraine compositions are sumatriptan, frovatriptan, and naratriptan.
It is desirable to provide a new route of administration for sumatriptan, frovatriptan, and naratriptan that rapidly produces peak plasma concentrations of the compounds. The provision of such a route is an object of the present invention.
SUMMARY OF THE INVENTION
The present invention relates to the delivery of anti-migraine compounds through an inhalation route. Specifically, it relates to aerosols containing sumatriptan, frovatriptan, or naratriptan that are used in inhalation therapy.
In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of sumatriptan, frovatriptan, or naratriptan. Preferably, the particles comprise at least 10 percent by weight of sumatriptan, frovatriptan, or naratriptan. More preferably, the particles comprise at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent or 99.97 percent by weight of sumatriptan, frovatriptan, or naratriptan.
Typically, the aerosol has a mass of at least 10 &mgr;g. Preferably, the aerosol has a mass of at least 100 &mgr;g. More preferably, the aerosol has a mass of at least 200 &mgr;g.
Typically, the particles comprise less than 10 percent by weight of sumatriptan, frovatriptan, or naratriptan degradation products. Preferably, the particles comprise less than 5 percent by weight of sumatriptan, frovatriptan, or naratriptan degradation products. More preferably, the particles comprise less than 2.5, 1, 0.5, 0.1 or 0.03 percent by weight of sumatriptan, frovatriptan, or naratriptan.
Typically, the particles comprise less than 90 percent by weight of water. Preferably, the particles comprise less than 80 percent by weight of water. More preferably, the particles comprise less than 70 percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10 percent, or 5 percent by weight of water.
Typically, at least 50 percent by weight of the aerosol is amorphous in form, wherein crystalline forms make up less than 50 percent by weight of the total aerosol weight, regardless of the nature of individual particles. Preferably, at least 75 percent by weight of the aerosol is amorphous in form. More preferably, at least 90 percent by weight of the aerosol is amorphous in form.
Typically, where the aerosol comprises sumatriptan, the aerosol has an inhalable aerosol drug mass density of between 5 mg/L and 40 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 10 mg/L and 35 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 15 mg/L and 30 mg/L.
Typically, where the aerosol comprises frovatriptan, the aerosol has an inhalable aerosol drug mass density of between 0.5 mg/L and 4 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 1 mg/L and 3.5 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 1.5 mg/L and 3.0 mg/L.
Typically, where the aerosol comprises naratriptan, the aerosol has an inhalable aerosol drug mass density of between 0.2 mg/L and 2 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 0.3 mg/L and 1.75 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 0.4 mg/L and 1.5 mg/L.
Typically, the aerosol has an inhalable aerosol particle density greater than 10
6
particles/mL. Preferably, the aerosol has an inhalable aerosol particle density greater than 10
7
particles/mL or 10
8
particles/mL.
Typically, the aerosol particles have a mass median aerodynamic diameter of less than 5 microns. Preferably, the particles have a mass median aerodynamic diameter of less than 3 microns. More preferably, the particles have a mass median aerodynamic diameter of less than 2 or 1 micron(s).
Typically, the geometric standard deviation around the mass median aerodynamic diameter of the aerosol particles is less than 3.0. Preferably, the geometric standard deviation is less than 2.5. More preferably, the geometric standard deviation is less than 2.2.
Typically, the aerosol is formed by heating a composition containing sumatriptan, frovatriptan, or naratriptan to form a vapor and subsequently allowing the vapor to condense into an aerosol.
In another composition aspect of the present invention, a dose form of an antimigraine compound is provided for the treatment of migraine, wherein the dose form comprises less than the typical oral dose of the antimigraine compound.
Typically, where the antimigraine compound is sumitriptan, the dose form comprises less than 20 mg of sumitriptan. Preferably, the dose form comprises less than 15 mg of sumitriptan. More preferably, the dose form comprises less than 10 mg or 5 mg of sumitriptan.
Typically, where the antimigraine compound is frovatriptan, the dose form comprises less than 2 mg of frovatriptan. Preferably, the dose form comprises less than 1.75 mg of frovatriptan. More preferably, the dose form comprises less than 1.5 mg, 1.25 mg or 1 mg of frovatriptan.
Typically, where the antimigraine compound is naratriptan, the dose form comprises less than 0.8 mg of naratriptan. Preferably, the dose form comprises less than 0.6 mg of naratriptan. More preferably, the dose for comprises less than 0.4 mg of naratriptan.
Typically, the dose form further comprises less than 90 percent by weight of water. Preferably, the dose form further comprises less than 80 percent by weight of water. More preferably, the dose form further comprises less than 70 percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, or 10 percent by weight of water.
Typically, the dose form further comprises less than 90 percent by weight of a pharmaceutically acceptable excipient. Preferably, the dose form further comprises less than 80 percent by weight of a pharmaceutically acceptable excipient. More preferably, the dose form further comprises less than 70 percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, or 10 percent by weight of a pharmaceutically acceptable excipient.
In a method aspect of the present invention, one of sumatriptan, frovatriptan, or naratriptan is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of sumatriptan, frovatriptan, or naratriptan, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. Preferably, the composition that is heated comprises at least 10 percent by weight of sumatriptan, frovatriptan, or naratriptan. More preferably, the composition comprises at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of sumatriptan, frovatriptan, or naratriptan.
Typically, the particles comprise at least 5 percent by weight of sumatriptan, frovatriptan, or naratriptan. Preferably, the particles comprise at least 10 percent by weight of sumatriptan, frovatriptan, or naratriptan. More preferably, the particles comprise at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of sumatriptan, frovatriptan, or naratriptan.
Typically, the aerosol has a mass of at lea
Hale Ron L.
Rabinowitz Joshua D.
Solas Dennis W.
Zaffaroni Alejandro C.
Alexza Molecular Delivery Corporation
Haghighatian Mina
Hartley Michael G.
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