Enzymatic debridement therapy for abnormal cell proliferation

Abstract

Compositions and methods are provided to destroy internal cancerous lesions selectively by the administration of a combination of a debridement protease enzyme and a denaturant of cell structural proteins and or cell adhesion proteins.

What is claimed is: 
     
         1 . A method for the treatment of a neoplasm, comprising administering to a patient in need thereof a treatment effective amount of a composition consisting essentially of one or more debridement enzyme and one or more denaturant, wherein the neoplasm is not a disorder of the skin. 
     
     
         2 . The method of  claim 1  wherein the debridement enzyme is selected from the group consisting of a plasma enzyme, a pancreatic enzyme, a cysteine protease, a serine protease, and a metallopeptidase. 
     
     
         3 . The method of  claim 1  wherein the debridement enzyme is selected from the group consisting of fibrinolysin, desoxyribonuclease, trypsin, chymotrypsin, krillase, bromelain, papain, ficin, subtilisins, proteinase K, collagenase, vibriolysin, thermolysin, streptokinase and streptodomase. 
     
     
         4 . The method of  claim 1  wherein the debridement enzyme is papain. 
     
     
         5 . The method of  claim 1  wherein the debridement enzyme is administered in a dose in the range 1×10 4  to 1×10 8  USP per gram. 
     
     
         6 . The method of  claim 1  wherein the debridement enzyme is administered in a dose of about 1.1×10 6  USP per gram. 
     
     
         7 . The method of  claim 1  wherein the denaturant is selected from the group consisting of urea, lactic acid, citric acid, an aliphatic alcohol, β-mercaptoethanol, a detergent, sodium dodecyl sulfate, formaldehyde, acetone, acetonitrile, dimethylsulfoxide, dimethylformamide, propylene carbonate, ethylene carbonate; a metal scavenger; crown ethers; a crown amine; a polyether; polyethyleneoxide; a polyamine; polyethyleneamine; cryptands; ethylenediaminetetraacetic acid or its salts; silver sulfadiazine; gentamicin; penicillin; a strong acid; hydrochloric acid; phosphoric acid; sulfuric acid; an acid with a pK a  less than about 4; a strong base; sodium hydroxide; potassium hydroxide; sodium carbonate; and a base with a pK a  greater than about 10. 
     
     
         8 . The method of  claim 1  wherein the denaturant is urea. 
     
     
         9 . The method of  claim 4  wherein the denaturant is urea. 
     
     
         10 . The method of  claim 0 .1-40 weight percent. 
     
     
         11 . The method of claim about 10 weight percent. 
     
     
         12 . The method of claim over 15 weight percent. 
     
     
         13 . The method of  claim 1  wherein the denaturant is present in concentration range of 1-5 weight percent. 
     
     
         14 . The method of  claim 1 , wherein the enzyme retains at least 80% activity at the concentrations of the denaturant. 
     
     
         15 . The method of  claim 1 , wherein the enzyme retains at least 90% activity at the concentrations of the denaturant is provided. 
     
     
         16 . The method of  claim 1 , wherein the enzyme retains at least 95% activity at the concentrations of the denaturant is provided. 
     
     
         17 . The method of  claim 1 , wherein the composition further comprises an enzyme stabilizing compound. 
     
     
         18 . The method of  claim 17 , wherein the enzyme stabilizing compound is selected from the group consisting of a sugar, monosaccharides, disaccharides, oligosaccharides, pyranose sugars, furanose sugars, glucose, lactose, sucrose, glycerol, pentaerythritol, polyhydric alcohols, O-phosphate derivatives of any of those compounds, 2,3-bisphosphoglycerate, manganese salts, iron salts, cobalt salts, nickel salts, copper salts, zinc salts, magnesium salts, calcium salts, sodium salts, potassium salts, and ammonium salts. 
     
     
         19 . The method of  claim 17 , wherein the combination is selected from:
 (a) papain, about 50 weight percent of lactose; and 10 weight percent urea;   (b) proteinase K, glucose, and a denaturant selected from the group consisting of urea, sodium dodecyl sulfate and ethylenediaminetetraacetic acid (EDTA); and   (c) porcine trypsin that has been modified by reductive methylation, glucose and a denaturant selected from the group consisting of 1M urea, 0.1% sodium dodecyl sulfate, 10% acetonitrile, and 2M guanidine hydrochloride; wherein the composition has a pH selected from the range of 7-9.   
     
     
         20 . The method of  claim 1 , wherein the composition is a hydrophilic ointment that additionally comprises:
 (a) an excipient selected from the group consisting of emulsifying wax fragrance, isopropyl palmitate, lactose, methylparaben, potassium phosphate monobasic, propylparaben, and purified water; and   (b) a buffer;   
       and wherein the ointment is administered in combination or alternation with one of the following:
 (c) a supplemental agent that minimizes damage to healthy normal cells from compounds released by dying cells, wherein the agent is optionally sodium copper chlorophyllin; or 
 (d) a cofactor selected from the group consisting of ATP, ADP, NAD, NADH, NADP, NADPH, oxidized and reduced flavins, folic acid, and folic acid derivatives. 
 
     
     
         21 . The method of  claim 1  wherein the lesion is selected from the group consisting of abdominal neoplasms, bone neoplasms, breast neoplasms, digestive system neoplasms, endocrine gland neoplasms, eye neoplasms, head and neck neoplasms, hematologic neoplasms, nervous system neoplasms, pelvic neoplasms, soft tissue neoplasms, splenic neoplasms, thoracic neoplasms, and urogenital neoplasms. 
     
     
         22 . The method of  claim 1  wherein the composition is administered by cannulation, injection or orally. 
     
     
         23 . The method of  claim 22  wherein the composition is in the form of a pill, a tablet, a capsule, a troche, or a medium comprising a controlled release polymer. 
     
     
         24 . The method of  claim 1  wherein the composition is in the form of a biodegradable surgical dressing that comprises the debridement enzyme and the denaturant. 
     
     
         25 . A method for the treatment of a neoplasm that is a disorder of the skin, comprising administering to a patient in need thereof a treatment effective amount of a composition consisting essentially of one or more debridement enzyme and one or more denaturant, wherein the composition is administered in combination with one or more of the following:
 a. an antioxidant;   b. an organic redox reagent;   c. an irradiation by infrared, ultraviolet, or ultrasonic energy; or   d. an enzyme that is capable of cleaving the backbone of a glycosaminoglycan.