Nitric oxide releasing suppositories and methods of use thereof

Abstract

The present invention relates generally to suppositories that release nitric oxide, and methods of using the same.

That which is claimed is: 
     
         1 . A suppository comprising:
 a nitric oxide-releasing active pharmaceutical ingredient; and   a suppository base.   
     
     
         2 . The suppository of  claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient is present in an amount of about 0.1% to about 70% by weight of the suppository. 
     
     
         3 . The suppository of  claim 1 , wherein the suppository releases nitric oxide in an amount of about 0.01% to about 10% by weight of the suppository, as measured by real time in vitro release testing. 
     
     
         4 . The suppository of  claim 1 , wherein the suppository base is present in an amount of about 0.01% to about 99.91% by weight of the suppository. 
     
     
         5 . The suppository of  claim 1 , wherein the suppository base comprises theobroma oil, triglyceride, monoglyceride and diglyceride esters of C 8 -C 20  fatty acids and the mixtures thereof, gelatin, polyethylene glycol (PEG), and/or glycerolated glycerin, and
 wherein the fatty acids comprise capric acid, caprylic acid, eicosenoic acid, stearic acid, lauric acid, myristic acid, oleic acid, palmitic acid, ricinoleic acid and their derivatives.   
     
     
         6 . The suppository of  claim 1 , wherein the suppository base is hydrophobic or hydrophilic. 
     
     
         7 . The suppository of  claim 1 , wherein the suppository further comprises a preservative in an amount of about 0.1% to about 2% by weight of the suppository. 
     
     
         8 . The suppository of  claim 7 , wherein the preservative comprises sorbic acid, benzoic acid, methyl-paraben, propyl-paraben, methylchloroisothiazolinone, metholisothiazolinone, diazolidinyl urea, chlorobutanol, triclosan, benzethonium chloride, p-hydroxybenzoate, chlorhexidine, digluconate, hexadecyltrimethyl ammonium bromide, alcohols, benzalkonium chloride, boric acid, bronopol, butylparaben, butylene calcium acetate, calcium chloride, calcium lactate, carbon dioxide, cationic, and bentonite, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, citric acid monohydrate, cresol, dimethyl ether, ethylparaben, glycerin, hexetidine, imidurea, isopropyl alcohol, lactic acid, monothioglycerol, pentetic acid, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium benzoate, potassium metabisulfite, potassium sorbate, propionic acid, propyl gallate, propylene glycol, sodium acetate, sodium benzoate, sodium borate, sodium lactate, sodium sulfite, sodium propionate, sodium metabisulfite, xylitol, sulphur dioxide, carbon dioxide, and any combination thereof. 
     
     
         9 . The suppository of  claim 1 , wherein the suppository further comprises a solvent in an amount of about 0.1% to about 99% by weight of the suppository. 
     
     
         10 . The suppository of  claim 9 , wherein the solvent comprises acetone, methyl alcohol, ethanol, isopropanol, butyl alcohol, ethyl acetate, dimethyl isosorbide, propylene glycol, glycerin, ethylene glycol, polyethylene glycol, diethylene glycol monoethyl ether, water, and mixtures thereof. 
     
     
         11 . The suppository of  claim 1 , wherein the suppository further comprises a lubricant in an amount of about 1% to about 10% by weight of the suppository. 
     
     
         12 . The suppository of  claim 11 , wherein the lubricant comprises magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and mineral oil, or combinations thereof. 
     
     
         13 . The suppository of  claim 1 , wherein the suppository further comprises mineral oil in an amount of about 1% to about 20% by weight of the suppository. 
     
     
         14 . The suppository of  claim 1 , wherein the suppository further comprises one or more hard waxes in an amount of about 1% to about 20% by weight of the suppository. 
     
     
         15 . The suppository of  claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a co-condensed silica network comprising diazeniumdiolated methylaminopropyl trimethoxysilane (MAP3) and tetraethyl orthosilicate (TEOS). 
     
     
         16 . The suppository of  claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a co-condensed silica network comprising diazeniumdiolated methylaminopropyl trimethoxysilane (MAP3), ethylaminoisobutylsiloxane (EAIB3), and tetraethyl orthosilicate (TEOS). 
     
     
         17 . The suppository of  claim 1 , wherein the suppository administers nitric oxide in an amount sufficient to induce apoptosis in virally infected cells. 
     
     
         18 . The suppository of  claim 1 , wherein the suppository administers nitric oxide in an amount sufficient to reduce or eliminate viral replication with less than about 50% host cell cytotoxicity. 
     
     
         19 . The suppository of  claim 1 , wherein the suppository is a vaginal suppository. 
     
     
         20 . A method of treating and/or preventing an infection in a subject in need thereof, the method comprising:
 administering a suppository to the subject,   wherein the suppository comprises a nitric oxide-releasing active pharmaceutical ingredient and a suppository base, thereby treating and/or preventing the infection in the subject.