Product and process for liquefaction of mucus or sputum

Abstract

Disclosed are compositions and methods for decreasing the viscosity and/or cohesiveness of and/or increasing the liquefaction of excessively or abnormally viscous or cohesive mucus or sputum. The composition contains a protein or peptide containing a thioredoxin active-site in reduced state and optionally further contains a reducing system.

1 . A method to increase the liquefaction of mucus or sputum in a patient that has excessively viscous or cohesive mucus or sputum, comprising contacting the mucus or sputum of the patient with a composition comprising a protein or peptide containing a thioredoxin active-site in reduced state effective to increase the liquefaction of the mucus or sputum as compared to prior to the step of contacting. 
     
     
         2 . The method of  claim 1 , wherein the patient has a lung disease in which abnormal or excessive viscosity or cohesiveness of mucus or sputum is a symptom or cause of the disease. 
     
     
         3 . The method of  claim 1 , wherein the patient has cystic fibrosis. 
     
     
         4 . The method of  claim 1 , wherein the step of contacting the mucus or sputum of the patient with the composition is performed by introducing the composition to the patient by a route selected from the group consisting of nasal, intratracheal, bronchial, direct installation into the lung and inhaled. 
     
     
         5 . The method of  claim 1 , wherein the mucus or sputum to be contacted is located in the respiratory tract, the gastrointestinal tract or the reproductive tract of the patient. 
     
     
         6 . The method of  claim 1 , wherein the composition is administered to the patient in a pharmaceutically acceptable carrier. 
     
     
         7 . The method of  claim 1 , wherein the protein or peptide is administered to the patient in an amount that is between about 1.5 mmoles/kg weight of the patient and about 150 mmoles/kg weight of the patient. 
     
     
         8 . The method of  claim 1 , wherein the protein has a half-life in the patient of between about 5 minutes and about 24 hours. 
     
     
         9 . The method of  claim 1 , wherein a liquid phase of a total volume of a sample of mucus or sputum from the patient shows a statistically significant increase after administration of the composition. 
     
     
         10 . The method of  claim 1 , wherein the thioredoxin active-site comprises the amino acid sequence C-X-X-C, wherein C residues are in reduced state, and wherein X residues are any amino acid residue. 
     
     
         11 . The method of  claim 1 , wherein the thioredoxin active-site comprises the amino acid sequence X-C-X-X-C-X, wherein C residues are in reduced state, and wherein X residues are any amino acid residue. 
     
     
         12 . The method of  claim 1 , wherein the thioredoxin active-site comprises the amino acid sequence X-C-G-P-C-X (SEQ ID NO:2), wherein C residues are in reduced state, and wherein X residues are any amino acid residue. 
     
     
         13 . The method of  claim 1 , wherein the thioredoxin active-site comprises the amino acid sequence W-C-G-P-C-K (SEQ ID NO:3), wherein C residues are in reduced state. 
     
     
         14 . The method of  claim 1 , wherein the protein comprises thioredoxin selected from the group consisting of prokaryotic thioredoxin, yeast thioredoxin, plant thioredoxin, and mammalian thioredoxin. 
     
     
         15 . The method of  claim 1 , wherein the protein comprises human thioredoxin. 
     
     
         16 . The method of  claim 1 , wherein the composition further comprises nicotinamide-adenine dinucleotide phosphate (reduced form) (NADPH) for reducing the thioredoxin active site of the protein. 
     
     
         17 . The method of  claim 16 , wherein the composition further comprises thioredoxin reductase. 
     
     
         18 . A composition for use in the liquefaction of mucus or sputum, comprising a protein or peptide containing a thioredoxin active-site in reduced state and at least one additional agent for treatment of excessively viscous or cohesive mucus or sputum. 
     
     
         19 . The composition of  claim 18 , wherein the thioredoxin active-site comprises the amino acid sequence X-C-X-X-C-X, wherein C residues are in reduced state, and wherein the X residues are any amino acid residue. 
     
     
         20 . The composition of  claim 18 , wherein the thioredoxin active-site comprises the amino acid sequence X-C-G-P-C-X (SEQ ID NO:2), wherein C residues are in reduced state, and wherein the X residues are any amino acid residue. 
     
     
         21 . The composition of  claim 18 , wherein the thioredoxin active-site comprises the amino acid sequence W-C-G-P-C-K (SEQ ID NO:3), wherein C residues are in reduced state. 
     
     
         22 . The composition of  claim 18 , wherein the protein comprises thioredoxin selected from a group consisting of prokaryotic thioredoxin, yeast thioredoxin, plant thioredoxin, and mammalian thioredoxin. 
     
     
         23 . The composition of  claim 18 , wherein the protein comprises human thioredoxin. 
     
     
         24 . The composition of  claim 18 , wherein the composition further comprises nicotinamide-adenine dinucleotide phosphate (reduced form) (NADPH). 
     
     
         25 . The composition of  claim 24 , wherein the composition further comprises thioredoxin reductase. 
     
     
         26 . A method to increase the liquefaction of mucus or sputum in a patient that has excessively viscous or cohesive mucus or sputum, comprising contacting the mucus or sputum in the respiratory tract of the patient with a composition comprising a protein comprising the amino acid sequence X-C-X-X-C-X, wherein C residues are in reduced state, wherein the contact of composition increases the volume of the liquid phase in a sample of mucus or sputum from the patient as compared to prior to contact with the composition.