Vitamin b12 nasal spray and method of use

Abstract

The present invention relates generally to vitamin 12 nasal spray compositions and methods of using the same in the treatment of vitamin B12 deficiency and various disorders that are related to such deficiency. In particular embodiments, the present invention is directed to treatment methods comprising intranasal administration of a cobalamin composition according to a particular dosing and frequency schedule and to a preservative-free nasal spray composition comprising a cobalamin compound useful in the practice of such treatment methods.

What is claimed is: 
     
         1 . A composition for nasal administration of cyanocobalamin, the composition comprising an aqueous solution containing about 1% w/w cyanocobalamin, a pharmaceutically acceptable buffer, a humectant, and a preservative, wherein:
 the buffer comprises a citrate buffer;   the humectant comprises glycerin;   the preservative comprises benzalkonium chloride;   the composition has a pH of about 4 to about 6.5, and   the composition is provided in a container equipped with a pump adapted to deliver the composition into a patient's nostril.   
     
     
         2 . The composition of  claim 1 , wherein the composition has a pH of about 5 to about 6.5. 
     
     
         3 . The composition of  claim 1 , wherein the composition has a pH of about 6 to about 6.5. 
     
     
         4 . The composition of  claim 1 , wherein the composition comprises about 0.001% w/w to about 5% w/w of preservative. 
     
     
         5 . The composition of  claim 1 , wherein the composition comprises about 0.01% w/w to about 1% w/w of preservative. 
     
     
         6 . The composition of  claim 1 , wherein the composition contains comprises 0.02% w/w to about 0.4% w/w of preservative. 
     
     
         7 . The composition of  claim 1 , wherein the composition comprises about 0.01% w/w to about 20% w/w of humectant. 
     
     
         8 . The composition of  claim 1 , wherein the composition further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of: surfactants, viscosity modifying agents, osmolarity adjusters, complexing agents, stabilizers, solubilizers, antioxidants, and any combination thereof. 
     
     
         9 . The composition of  claim 8 , wherein the composition comprises about 0.1% w/w to about 50% w/w of surfactant. 
     
     
         10 . The composition of  claim 1 , wherein the composition further comprises a surfactant selected from the group consisting of: polyoxyethylene derivatives of fatty acids, partial esters of sorbitol anhydrides, sodium lauryl sulfate, sodium salicylate, oleic acid, lecithin, dehydrated alcohol, Tween, Span, polyoxyl 40 stearate, polyoxy ethylene 50 stearate, edetate disodium, propylene glycol, glycerol monooleate, fusieates, bile salts, octoxynol, and combinations thereof. 
     
     
         11 . The composition of  claim 8 , wherein the composition comprises about 0.1% w/w to about 20% w/w of viscosity modifying agent. 
     
     
         12 . The composition of  claim 1 , wherein the composition further comprises a viscosity modifying agent selected from the group consisting of: methyl cellulose, xanthan gum, carboxymethyl cellulose, hydroxypropyl cellulose, carbomer, polyvinyl alcohol, alginates, acacia, chitosans, and combinations thereof. 
     
     
         13 . The composition of  claim 8 , wherein the composition comprises about 0.01% w/w to about 5% w/w of antioxidant. 
     
     
         14 . The composition of  claim 1 , wherein the composition further comprises an antioxidant selected from the group consisting of: sodium metabisulfite, potassium metabisulfite, ascorbyl palmitate, and combinations thereof. 
     
     
         15 . The composition of  claim 1 , wherein the aqueous solution is isotonic. 
     
     
         16 . The composition of  claim 15 , wherein the solution has an osmolarity of from about 230 mOsmols to about 340 mOsmols. 
     
     
         17 . The composition of  claim 15 , wherein the solution has an osmolarity of from about 280 mOsmols to about 290 mOsmols 
     
     
         18 . The composition of  claim 1 , wherein the container is further equipped with a metering valve for dispensing a predetermined volume of the composition. 
     
     
         19 . A composition for nasal administration of cyanocobalamin, the composition comprising an aqueous solution containing about 1% w/w cyanocobalamin, a citrate buffer, glycerin in an amount of about 0.01% w/w to about 20% w/w, and benzalkonium chloride in an amount of about 0.001% w/w to about 5% w/w, wherein the composition has a pH of about 4 to about 6.5, and wherein the composition is provided in a container equipped with a pump adapted to deliver the composition into a patient's nostril.