Niclosamide nasal and throat spray

Abstract

The present disclosure provides prophylactic nasal and throat sprays that can be used to prevent initial infection of COVID19, its more contagious variants, and other respiratory viral infections, and the methods of making of the same. Data is given in a series of embodiments that show how niclosamide from one supplier (AK Sci), who's initial powder has a block-like morphology of what appears to be a high solubility polymorph, readily dissolves in pH buffers providing increased amounts in solution as the solution pH is increased. Unlike more conventional particulate drug materials, this provides 20 uM to 30 uM solutions of niclosamide at pH 8 for a prophylactic, preventative nasal spray that has rapid permeation through the nasal mucin and direct access to the underlying epithelial cells that the virus infects. At higher pH of 9.2 it can provide a 300 uM solution of niclosamide for throat spray to be used at first signs of early infection. Another embodiment shows that niclosamide from a second supplier (Sigma), that already contains some of the low solubility most stable polymorph (the monohydrate) gives an initial dissolution (3 hrs) that is similar to the AK Sci material, overnight stirring converts the powdered excess niclosamide to the more stable and lower solubility polymorph. A further embodiment shows how niclosamide from commercially available tablets (Yomesan) can be extracted into aqueous pH solution that does not involve the use of organic solvents. Additional embodiments show a solvent injection technique can be used to make supersaturated solutions of niclosamide that eventually precipitate and also form the low solubility monohydrate polymorph as do water, acetone, and ethanol niclosamide cosolvates. The solvent injection technique is the preferred method to make niclosamide solutions at concentrations where it is soluble because the initial powdered material can be dissolved in ethanol, any microparticulate impurities filtered out, and a clear solution made that is not in contact or equilibrium with any powdered material, that if it forms the monohydrate polymorph would reduce the amount of niclosamide in solution and therefore reduce its bioavailability to the nasal and respiratory epithelium.

Dependencies are inferred from the claim text.