Pharmaceutical compositions and methods utilizing neostigmine and an NK-1 antagonist for treating myasthenia gravis
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12023315-B2
Publication Date
2024-07-02
Expiration Date
Abstract
The present invention describes the administration of an NK1 antagonist, in combination with neostigmine methylsulfate, intravenously, via subcutaneous infusion, or both intravenously and via subcutaneous infusion to facilitate the treatment of a patient suffering from myasthenia gravis by providing a therapeutically effective neostigmine methylsulfate daily dose without the dose-limiting gastrointestinal adverse effects associated with neostigmine methylsulfate.
Core Innovation
The invention provides a method of treating symptoms of muscle weakness associated with myasthenia gravis or another myasthenic syndrome in a mammalian subject. The method comprises chronically administering, through parenteral administration, a therapeutically effective dose of a neurokinin 1 (NK1) antagonist selected from aprepitant, fosaprepitant, rolapitant, netupitant, or pharmaceutically acceptable salts of these NK1 antagonists, co-administered with chronically administered neostigmine.
The method further comprises chronically administering intravenously and/or through subcutaneous infusion a daily dose equivalent of neostigmine methylsulfate. The NK1 antagonist is used to enable therapeutically effective neostigmine dosing while attenuating or eliminating neostigmine’s gastrointestinal dose-limiting adverse effects.
Combinations and formulations are described for oral dosing and parenteral administration routes including intravenous, subcutaneous infusion, including 24-hour infusion, and transdermal administration. The disclosure includes fixed-dose combinations or kits and lists NK1 antagonists such as aprepitant, fosaprepitant, rolapitant, netupitant and related salts or prodrugs.
Claims Coverage
The independent claim covers a chronically administered, parenteral co-treatment regimen that combines a selected NK1 antagonist with neostigmine methylsulfate for treating muscle weakness symptoms associated with myasthenia gravis or another myasthenic syndrome. The claim includes three inventive features and specifies parenteral administration routes for the neostigmine methylsulfate component and an NK1-antagonist co-administered regimen.
Chronic parenteral NK1 antagonist plus neostigmine methylsulfate for myasthenia gravis muscle weakness
A method of treating symptoms of muscle weakness associated with myasthenia gravis or another myasthenic syndrome by chronically administering, through parenteral administration, a therapeutically effective dose of an NK1 antagonist selected from aprepitant, fosaprepitant, rolapitant, netupitant, or pharmaceutically acceptable salts thereof, and chronically administering a daily dose equivalent of neostigmine methylsulfate to the mammalian subject.
NK1 antagonist selected from specified agents and salts
The NK1 antagonist is selected from aprepitant, fosaprepitant, rolapitant, netupitant, and pharmaceutically acceptable salts of these NK1 antagonists.
Parenteral route for neostigmine methylsulfate via intravenous and/or subcutaneous infusion
The method includes chronically administering neostigmine methylsulfate intravenously, through subcutaneous infusion, or both.
The core coverage is a chronic co-administration approach using a selected NK1 antagonist together with chronically administered neostigmine methylsulfate for treating muscle weakness symptoms associated with myasthenia gravis or another myasthenic syndrome, using parenteral administration including intravenous and/or subcutaneous infusion.
Stated Advantages
Attenuation or elimination of neostigmine’s gastrointestinal dose-limiting adverse effects.
Documented Applications
Treating symptoms of muscle weakness associated with myasthenia gravis or another myasthenic syndrome in a mammalian subject.
A Phase I study concept using aprepitant to attenuate gastrointestinal side effects of high/effective neostigmine bromide doses in healthy human subjects.
Interested in licensing this patent?