Niclosamide formulations for treating disease

Abstract

The invention relates to a method of treating a viral infection caused by or associated with SARS-CoV-2 in a subject, the method comprising administering to the subject by inhalation intraorally and/or intranasally a therapeutically effective amount of a formulation comprising niclosamide, or a pharmaceutically acceptable salt thereof, and a cyclodextrin.

1 .- 21 . (canceled) 
     
     
         22 . An intranasal delivery device comprising a liquid formulation, wherein the liquid formulation comprises:
 about 0.1% to about 1.5% niclosamide or a pharmaceutically acceptable salt thereof;   about 1% to about 25% hydroxypropyl β-cyclodextrin;   about 0.1% to about 5% polyvinylpyrrolidone;   the balance being water,   wherein the percentages are by weight based on the weight of the liquid formulation.   
     
     
         23 . The intranasal delivery device of  claim 22 , wherein the niclosamide, or a pharmaceutically acceptable salt thereof, is niclosamide ethanolamine. 
     
     
         24 . The intranasal delivery device of  claim 22 , wherein the niclosamide, or a pharmaceutically acceptable salt thereof, is niclosamide. 
     
     
         25 . The intranasal delivery device of  claim 22 , wherein the liquid formulation is in the form of a solution, suspension or dispersion of the niclosamide or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The intranasal delivery device of  claim 22 , wherein the niclosamide, or a pharmaceutically acceptable salt thereof, is present in the liquid formulation in an amount of about 1% by weight of the formulation. 
     
     
         27 . The intranasal delivery device of  claim 22 , wherein the niclosamide, or a pharmaceutically acceptable salt thereof, is present in the liquid formulation in an amount of about 0.1% by weight of the formulation. 
     
     
         28 . The intranasal delivery device of  claim 22 , wherein the hydroxypropyl β-cyclodextrin is present in the liquid formulation in an amount of from about 10% to about 20% by weight of the formulation. 
     
     
         29 . The intranasal delivery device of  claim 22 , wherein the hydroxypropyl β-cyclodextrin is present in the liquid formulation in an amount of about 15% by weight of the formulation. 
     
     
         30 . The intranasal delivery device of  claim 22 , wherein the niclosamide, or a pharmaceutically acceptable salt thereof, is present in the liquid formulation in an amount of about 1% by weight of the formulation and the hydroxypropyl β-cyclodextrin is present in the liquid formulation in an amount of about 11% to about 17% by weight of the formulation. 
     
     
         31 . The intranasal delivery device of  claim 22 , wherein the polyvinylpyrrolidone is PVP K30. 
     
     
         32 . The intranasal delivery device of  claim 22 , wherein the polyvinylpyrrolidone is present in the liquid formulation in an amount of from about 1% to about 4% by weight of the formulation. 
     
     
         33 . The intranasal delivery device of  claim 22 , wherein the polyvinylpyrrolidone is present in the liquid formulation in an amount of from about 0.1% to about 3% by weight of the formulation. 
     
     
         34 . The intranasal delivery device of  claim 22 , wherein the niclosamide, or a pharmaceutically acceptable salt thereof, is present in the liquid formulation in an amount of about 1% by weight of the formulation and the polyvinylpyrrolidone is present in the liquid formulation in an amount of about 1% to about 3% by weight of the formulation. 
     
     
         35 . The intranasal delivery device of  claim 22 , wherein the liquid formulation has a pH of from 7.6 to 8.0. 
     
     
         36 . The intranasal delivery device of  claim 22 , wherein the liquid formulation has a pH of about 7.8. 
     
     
         37 . The intranasal delivery device of  claim 22 , wherein the liquid formulation has an osmolality of from about 250 to about 350 mOsmol/kg. 
     
     
         38 . The intranasal delivery device of  claim 22 , wherein the liquid formulation has an osmolality of from about 280 to about 330 mOsmol/kg. 
     
     
         39 . The intranasal delivery device of  claim 22 , wherein the liquid formulation has a pH of from 7.6 to 8.0 and an osmolality of from about 250 to about 350 mOsmol/kg. 
     
     
         40 . The intranasal delivery device of  claim 22 , wherein the liquid formulation does not comprise a preservative. 
     
     
         41 . The intranasal delivery device of  claim 22 , wherein the liquid formulation comprises:
 0.5-1.5% niclosamide or a pharmaceutically acceptable salt thereof;   5-20% hydroxypropyl β-cyclodextrin;   0.5-5% polyvinylpyrrolidone;   the balance being water,   wherein the percentages are by weight based on the weight of the liquid formulation; and
 wherein the liquid formulation has a pH of from 7.6 to 8.0. 
   
     
     
         42 . The intranasal delivery device of  claim 41 , wherein the niclosamide, or a pharmaceutically acceptable salt thereof, is niclosamide ethanolamine. 
     
     
         43 . The intranasal delivery device of  claim 41 , wherein the liquid formulation has a pH of about 7.8. 
     
     
         44 . The intranasal delivery device of  claim 41 , wherein the liquid formulation has an osmolality of from about 250 to about 350 mOsmol/kg. 
     
     
         45 . The intranasal delivery device of  claim 41 , wherein the liquid formulation has an osmolality of from about 280 to about 330 mOsmol/kg. 
     
     
         46 . The intranasal delivery device of  claim 41 , wherein the liquid formulation has a pH of about 7.8 and an osmolality of from about 250 to about 350 mOsmol/kg. 
     
     
         47 . The intranasal delivery device of  claim 41 , wherein the polyvinylpyrrolidone is PVP K30. 
     
     
         48 . The intranasal delivery device of  claim 41 , wherein the liquid formulation does not comprise a preservative. 
     
     
         49 . The intranasal delivery device of  claim 22 , wherein the liquid formulation comprises:
 about 1% niclosamide ethanolamine;   about 15% hydroxypropyl β-cyclodextrin;   about 2% PVP;   the balance being water,   wherein the percentages are by weight based on the weight of the liquid formulation; and   wherein the formulation has a pH of from 7.6 to 8.0.   
     
     
         50 . The intranasal delivery device of  claim 49 , wherein the formulation has a pH of about 7.8. 
     
     
         51 . The intranasal delivery device of  claim 49 , wherein the liquid formulation has an osmolality of from about 250 to about 350 mOsmol/kg. 
     
     
         52 . The intranasal delivery device of  claim 49 , wherein the liquid formulation has a pH of about 7.8 and an osmolality of from about 250 to about 350 mOsmol/kg. 
     
     
         53 . The intranasal delivery device of  claim 49 , wherein the PVP is PVP K30. 
     
     
         54 . The intranasal delivery device of  claim 49 , wherein the liquid formulation does not comprise a preservative. 
     
     
         55 . The intranasal delivery device of  claim 22 , wherein the device is adapted to deliver the liquid formulation in the form of a spray. 
     
     
         56 . The intranasal delivery device of  claim 22 , wherein the device is adapted to deliver a unit dose of the liquid formulation in an amount of from 100 to 200 μL. 
     
     
         57 . The intranasal delivery device of  claim 22 , wherein the device is adapted to deliver a unit dose of the liquid formulation in an amount of from 130 to 150 μL. 
     
     
         58 . The intranasal delivery device of  claim 22 , wherein the device is selected from a dropper, a metered dose spray pump, a squeeze bottle, a single-dose or duo-dose spray device, a nasal pressurized metered-dose inhaler, a pulsation membrane nebulizer, a nasal sonic/pulsating jet nebulizer, a vibrating mesh nebulizer, a nasal atomizer and a gas- or electrically-driven atomizer. 
     
     
         59 . The intranasal delivery device of  claim 22 , wherein the device is a metered dose spray pump. 
     
     
         60 . The intranasal delivery device of  claim 59 , wherein the metered dose spray pump comprises a collapsible bag, a moveable piston or a compressed gas adapted to replace the liquid formulation emitted from the device. 
     
     
         61 . The intranasal delivery device of  claim 60 , wherein the liquid formulation does not comprise a preservative. 
     
     
         62 . The intranasal delivery device of  claim 59 , wherein the metered dose spray pump comprises a filter adapted to decontaminate air that enters the device to replace the liquid formulation emitted from the device. 
     
     
         63 . The intranasal delivery device of  claim 62 , wherein the liquid formulation does not comprise a preservative. 
     
     
         64 . The intranasal delivery device of  claim 22 , wherein the device is a single-dose or duo-dose spray device.