Use of hydrolytic and oxidative enzymes to dissolve biofilm in airway passages

Abstract

A composition for removal of biofilm in the airway passage is useful for the treatment of infections such as pneumonia cause by Mycoplasma pneumoniae . In general, the composition comprises: (1) a quantity of at least one enzyme that catalyzes the hydrolysis of a bond that connects two monosaccharides in a polysaccharide or that connects a monosaccharide with a protein molecule in a glycoprotein sufficient to break down biofilm in the airway; and (2) a pharmaceutically acceptable carrier suitable for administration into the airway. The composition can further include ingredients such as a steroid, lysozyme, lactoferrin, or a peroxidase; if a peroxidase is included, the composition can further include an oxidase to generate peroxide as well as a substrate for the oxidase. The composition can be used in methods for treatment of an infection based on the ability of the composition to dissolve biofilm in the airway.

1 .- 115 . (canceled) 
     
     
         116 . A composition for the removal of biofilm in airway passages comprising:
 (a) a quantity of at least one enzyme that catalyzes the hydrolysis of a bond that connects two monosacchrides in a polysaccharide or that connects a monosacchride with a protein molecule in a glycoprotein sufficient to break down biofilm in airway passages; and   (b) a pharmaceutically acceptable carrier suitable for administration into the airway.   
     
     
         117 . The composition of  claim 116  wherein the at least one enzyme that catalyzes the hydrolysis of a bond that connects two monosacchrides in a polysaccharide or that connects a monosacchride with a protein molecule in a glycoprotein is selected from the group consisting of xylanase, β-glucanase, cellulose, α-galactosidase, glucanases, amylase, hyaluronidase, polygalacturonase (pectinase), dextranase, cellobiohydrolase, pullulanase, glycosylceramidase, glucan 1,4-α-glucosidase, oligo-1,6-glucosidase, fucoidanase, glycosylceramidase, thioglucosidase, and glycopeptides N-glycosidase. 
     
     
         118 . The composition of  claim 116  wherein the composition further comprises at least one ingredient in a quantity effective to prevent or inhibit inflammation in the airway. 
     
     
         119 . The composition of  claim 118  wherein the at least one ingredient in a quantity effective to prevent or inhibit inflammation in the airway is a steroid. 
     
     
         120 . The composition of  claim 119  wherein the steroid is a steroid selected from the group consisting of hydrocortisone, beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, methylprednisone, prednisolone, prednisone, and triamcinolone, and the salts, solvates, analogues, congeners, bioisosteres, hydrolysis products, metabolites, precursors, and prodrugs thereof. 
     
     
         121 . The composition of  claim 116  wherein the pharmaceutically acceptable carrier suitable for administration into the airway includes propylene glycol, glycerol, or tripropylene glycol. 
     
     
         122 . The composition of  claim 116  wherein the composition further comprises an antibiotic that is effective in the treatment of  Mycoplasma pneumonia  in a quantity effective to exert a bactericidal action against  M. pneumonia  selected from the group consisting of amikacin, ticarcillin, piperacullin, mezlocillin, azlocillin, ceftazidime, cefepime, ciprofloxacin, tobramycin, aztreonam, imipenem, meropenem, lysozyme, and lactoferrin. 
     
     
         123 . The composition of  116  further including at least one peroxidase in a quantity sufficient to exert a bactericidal action. 
     
     
         124 . The composition of  claim 123  wherein the at least one peroxidase is selected from the group consisting of lactoperoxidase, myeloperoxidase, horseradish peroxidase, eosinophil peroxidase, and glutathione peroxidase. 
     
     
         125 . The composition of  claim 123  wherein the composition further includes at least one substrate that can be converted to an ion with bactericidal properties by the enzymatic action of the peroxidase in a quantity such that an effective concentration of the ion with bactericidal properties is produced by the catalytic action of the peroxidase. 
     
     
         126 . The composition of  claim 125  wherein the at least one substrate is an alkali metal salt of thiocyanate, iodate, or cholarate. 
     
     
         127 . The composition of  claim 123  wherein the composition further includes a catalase inhibitor. 
     
     
         128 . The composition of  claim 125  wherein the composition further includes an aminohexose in a quantity effective to increase the yield or accumulation of oxidized anionic biocidal agent. 
     
     
         129 . The composition of  claim 123  wherein the oxidase is selected from the group consisting of glucose oxidase, galactose oxidase, urate oxidase, choline oxidase, D-amino acid oxidase, D-glutamate oxidase, glycine oxidase, glycolic oxidase, L-sorbose oxidase, alcohol oxidase, and amine oxidase. 
     
     
         130 . A method of treating an airway infection comprising the step of administering a quantity of the composition of  claim 116  to a subject with an airway infection in order to treat the infection. 
     
     
         131 . The method of  claim 130 , wherein the airway infection is pneumonia. 
     
     
         132 . The method of  claim 130 , wherein the method further comprises administering an antibiotic that is effective against  M. pneumoniae in a quantity effective to exert a bactericidal action against  M. pneumoniae . 
     
     
         133 . The method of  claim 132 , wherein the composition is delivered to the subject via the same route of administration as the antibiotic. 
     
     
         134 . The method of  claim 132 , wherein the composition is delivered to the subject via a different route of administration as the antibiotic.