Acidified nitrite as an antimicrobial agent

Abstract

The present invention provides a dosage form for the treatment of bacterial, viral or fungal conditions which comprises, a pharmaceutically acceptable acidifying agent in an amount sufficient to reduce the pH at an environment of use to below pH4, and a pharmaceutically acceptable source of nitrite ions or a nitrate precursor therefor; wherein said acidifying agent and said source of nitrite ions or nitrate precursor are separately disposed in respective pharmaceutically acceptable carriers for admixture at the intended environment of use to release NO or NO 2 ions. The invention also provides delivery systems for the topical medicament.

What we claim is:  
     
         1 . A dosage form for the treatment of bacterial, viral or fungal conditions which comprises, 
 a pharmaceutically acceptable acidifying agent in an amount sufficient to reduce the pH at an environment of use to below pH4, and    a pharmaceutically acceptable source of nitrite ions or a nitrate precursor therefor;    wherein said acidifying agent and said source of nitrite ions or nitrate precursor are separately disposed in respective pharmaceutically acceptable carriers for admixture at the intended environment of use to release NO or NO 2  ions.    
     
     
         2 . A dosage form according to  claim 1  wherein the acidifying agent is an acid or an acid salt.  
     
     
         3 . A dosage form according to  claim 1  wherein the pharmaceutically acceptable carriers are selected from inert creams, ointments, tablets or are in liquid form.  
     
     
         4 . A dosage form according to  claim 1  wherein the condition to be treated is caused by an organism selected from the group consisting of Albicans sp., Leishmania sp., Staphylococcus sp., Francisella sp., Microbacterium,  E.coli Tinea pedis, Heliobacter pylorii  and  amoebic dysentery.    
     
     
         5 . A dosage form according to  claim 1  used to treat a fungal infection of the feet.  
     
     
         6 . A dosage form according to  claim 1  wherein the condition for treatment is virus mediated.  
     
     
         7 . A dosage form adapted for the treatment of a virus mediated condition by topical application of a medicament to or adjacent to an environment of use, comprising an admixture of nitrogen oxides generated at the environment of use from a pharmaceutically acceptable acidifying agent in an amount sufficient to reduce the pH or the environment of use to below pH, and a pharmaceutically acceptable source of nitrogen oxides or a nitrate precursor therefor.  
     
     
         8 . A dosage form according to  claim 7  where the acidifying agent is also a reducing agent.  
     
     
         9 . A dosage form according to  claim 7  when the acidifying agent is present in an amount sufficient to reduce the pH at the environment of use to a value above pH2.  
     
     
         10 . A dosage form according to  claim 7  wherein the nitrogen oxides are derived from an inorganic nitrite.  
     
     
         11 . A dosage form according to  claim 7  where the pharmaceutically acceptable acidifying agent is selected from absorbic and, ascorbyl palmitate, salicylic acid, lactic acid, citric acid, benzoic acid and tartaric acid.  
     
     
         12 . A dosage form according to  claim 7  wherein the source of nitrogen acids is an alkali metal nitrite or precursor therefor and constitutes 0.5 to 30% by weight of the total dosage form.  
     
     
         13 . A dosage form according to  claim 7  wherein the virus condition is engendered by molluscum contagiosum, herpes simplex types 1 & 2, valicella zoster virus, and papilloma virus  
     
     
         14 . A delivery system for the topical application of a medicament for the in vivo treatment of the epidermis, comprising an adhesive layer and a support layer impregnated with at least one of the components of the medicament characterized in that the components of the medicament comprise separately a pharmaceutically acceptable acidifying agent and a pharmaceutically acceptable source of nitrogen oxides or a precursor therefor, and a means for combining the pharmaceutically acceptable acidifying agent with the source of nitrogen oxides at the environment of use.  
     
     
         15 . A delivery system according to  claim 14  wherein the delivery system comprises microspheres.  
     
     
         16 . A delivery system according to  claim 14  wherein the delivery system comprises liposomes.  
     
     
         17 . A two-part delivery system for topical application of a medicament for the in vivo treatment of a viral, bacterial or fungal infection of the epidermis, said system comprising separately; 
 (a) a first waxy component comprising a pharmaceutically acceptable acidifying agent; and    (b) a second waxy component comprising a pharmaceutically acceptable source of nitrogen oxides, whereby when topically applied simultaneously or immediately sequentially to an environment of use, active nitrogen oxides are released thereto.    
     
     
         18 . A delivery system according to  claim 17  wherein the acidifying agent is a reducing organic acid or salt.