Compositions and methods comprising serratia peptidase for inhibition and treatment of biofilms related to certain conditions

Abstract

Physiologically acceptable anti-biofilm compositions comprising Serratia peptidase and optionally one or more of bromelain, papain and a fibrinolytic enzyme. Additional components can include antimicrobials, antibiotics, antifungals, herbals, chelating agents, lactoferrin and related compounds, minerals, surfactants, binders, and fillers useful for the inhibition and treatment of gastrointestinal biofilms in humans. Physiologically acceptable anti-biofilm compositions containing these enzymes are useful in the inhibition, reduction and/or treatment of biofilms such as in the ear, vagina, joints, bones, gut, surgical sites and other locations, and are useful for the inhibition, reduction and/or treatment of associated systemic symptoms caused by biofilm associated microorganisms.

What is claimed is: 
     
         1 . A physiologically acceptable anti-biofilm composition suitable for administration to a mammal, the composition comprising at least one pharmaceutically acceptable carrier and  Serratia  peptidase, bromelain, papain and a fibrinolytic enzyme in amounts capable of significant biofilm degradation in the mammal upon administration to the mammal. 
     
     
         2 . The composition of  claim 1  wherein the fibrinolytic enzyme comprises at least one of nattokinase or lumbrokinase. 
     
     
         3 . The composition of  claim 2 , wherein the composition is configured for oral administration such that the composition is capable of gastrointestinal absorption while retaining the anti-biofilm activity after passing through the stomach. 
     
     
         4 . The composition of  claim 1 , wherein the composition is configured for topical administration while retaining the anti-biofilm activity. 
     
     
         5 . The composition of  claim 1 , wherein the composition further comprises at least one chelating agent capable of chelating at least one of calcium or iron configured for administration in an amount capable of significant biofilm degradation in the mammal. 
     
     
         6 . The composition of  claim 5 , wherein the chelating agent is at least one of lactoferrin or a lactoferrin peptide capable of chelation. 
     
     
         7 . The composition of any one of  claim 1 , wherein the composition further comprises at least one of an anti-biofilm acid-stable cellulase or an anti-biofilm anti-polymeric β-1,6-N-acetyl-D-glucosamine (poly-β-1,6-GlcNAc) agent configured for administration in an amount capable of significant biofilm degradation in the mammal. 
     
     
         8 . The composition of any one of  claim 1 , wherein the composition further comprises at least one of an acid-stable hemicellulase/pectinase complex, β-gluconase, acid protease, or alkaline protease configured for administration in an amount capable of significant biofilm degradation in the mammal. 
     
     
         9 . The composition of  claim 1 , wherein the physiologically acceptable anti-biofilm composition further comprises at least one acid-stable agent configured in an amount capable of significant biofilm degradation in the mammal, the at least one acid-stable agent selected from the following: a disaccharidase; amylase; α-amylase; β-amylase; glucoamylase; endoglucanase; xylanase; lipase; lysozyme; an enzyme with dipeptidyl peptidase IV (DPP-IV) activity; chitosanase; ficin; kiwi protease; any plant-derived protease or proteinase, or phytase. 
     
     
         10 . The composition of  claim 1 , wherein the physiologically acceptable anti-biofilm composition further comprises at least one acid-stable enzyme configured for administration in an amount capable of significant biofilm degradation in the mammal, the at least one enzyme selected from the following: 1,2-1,3-α-D-mannan mannohydrolase, 1,3-β-D-xylanxylanohydrolase, 1,3-β-D-glucan glucanohydrolase, 1,3(1,3;1,4)-α-D-glucan 3-glucano-hydrolase, 1,3(1,3;1, 4)-β-D-glucan 3(4)-glucanohydrolase, 1,3-1,4-α-D-glucan 4-glucanohydrolase, 1,4-α-D-glucan glucanohydrolase, 1,4-α-D-glucan glucohydrolase, 1,4-(1,3:1,4)-β-D-glucan 4-glucanohydrolase, 1,4-β-D-glucan glucohydrolase, 1,4-β-D-xylan xylanohydrolase, 1,4-β-D-mannan mannanohydrolase, 1,5-α-L-arabinanohydrolase, 1,4-α-D-glucan maltohydrolase, 1,6-α-D-glucan 6-glucanohydrolase, 2,6-β-fructan fructanohydrolase, α-dextrin 6-glucanohydrolase, α-D-galactoside galactohydrolase, α-D-glucoside gluco-hydrolase, α-D-mannoside mannohydrolase, acylneuraminyl hydrolase, Aerobacter-capsular-polysaccharide galactohydrolase, β-D-fructofuranoside fructohydrolase, β-D-fucoside fucohydrolase, α-D-fructan fructohydrolase, β-D-galactoside galactohydrolase, β-D-glucoside glucohydrolase, β-D-glucuronoside, glucuronosohydrolase, β-D-mannoside mannohydrolase, β-N-acetyl-D-hexosaminide N-acetylhexosamino hydrolase, cellulose-sulfate sulfohydrolase, collagenase, dextrin 6-α-D-glucanohydrolase, glycoprotein phosphatidylinositol phosphatido-hydrolase, hyaluronate 4-glycanohydrolase, hyaluronoglucuronidase, pectin pectylhydrolase, peptidoglycan N-acetylmuramoylhydrolase, phosphatidylcholine 2-acylhydrolase, phosphatidyl-choline 1-acylhydrolase, poly(1,4-α-D-galacturonide), poly(1,4-(N-acetyl-β-D-glucosaminide))-glycanohydrolase, proteases, sucrose α-glucosidase, triacylglycerol acylhydrolase, and triacylglycerol protein-acylhydrolase. 
     
     
         11 . The composition of any one of  claim 1 , wherein the composition further comprises a green tea extract configured for administration in an amount capable of significant biofilm degradation in the mammal. 
     
     
         12 . The composition of any one of  claim 1 , wherein the composition further comprises at least one of an acid-stable subtilisin and an acid-stable DNAse I configured for administration in an amount capable of significant biofilm degradation in the mammal. 
     
     
         13 . The composition of any one of  claim 1 , wherein the composition further comprises, in an amount capable of significant biofilm degradation in the mammal, a chelating agent selected from the group comprising ethylenediamine-N,N,N′,N′-tetraacetic acid (EDTA); the disodium, trisodium, tetrasodium, dipotassium, tripotassium, dilithium and diammonium salts of EDTA; the barium, calcium, cobalt, copper, dysprosium, europium, iron, indium, lanthanum, magnesium, manganese, nickel, samarium, strontium, and zinc chelates of EDTA; trans-1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid monohydrate; N,N-bi s(2-hydroxyethyl)glycine; 1,3-diamino-2-hydroxypropane-N,N,N′,N′-tetraacetic acid; 1,3-diaminopropane-N,N,N′,N′-tetraacetic acid; ethylenediamine-N,N′-diacetic acid; ethylenediamine-N,N′-dipropionic acid dihydrochloride; ethylenediamine-N,N′-bis(methylenephosphonic acid)hemihydrate; N-(2-hydroxyethyl)ethyl enediamine-N,N′,N′-triacetic acid; ethylenediamine-N,N,N′,N′-tetrakis-(methylenephosponic acid); O,O′-bis(2-aminoethyl)ethyl eneglycol-N,N,N′,N′-tetraacetic acid; N,N-bi s(2-hydroxybenzyl)ethylene diamine-N,N-diacetic acid; 1,6-hexamethylenedi amine-N,N,N′,N′-tetraacetic acid; N-(2-hydroxyethyl)iminodiacetic acid; iminodiacetic acid; 1,2-diaminopropane-N,N,N′,N′-tetraacetic acid; nitrilotriacetic acid; nitrilotripropionic acid; the trisodium salt of nitrilotris(methylenephosphoric acid); 7,19,30-trioxα-1,4,10,13,16,22,27,33-octaazabicyclo[11,11,11]pentatriacontane hexahydrobromide; deferiprone; triethylenetetraminie-N,N,N′,N″,N′″,N′″-hexaacetic acid; deferoxamine; and deferasirox. 
     
     
         14 . The composition of any one of  claim 1 , wherein the composition further comprises an antibiotic. 
     
     
         15 . The composition of any one of  claim 1 , wherein the composition does not comprise an antibiotic. 
     
     
         16 . The composition of any one of  claim 1 , wherein the composition further comprises quercetin. 
     
     
         17 . The composition of any one of  claim 1 , wherein the composition further comprises seaprose. 
     
     
         18 . The composition of any one of  claim 1 , wherein the composition further comprises  Fusarium  protease.