Graft prosthesis, materials and methods

Abstract

A graft prostheses ( 11 ), materials and method for implanting, transplanting, replacing, or repairing a part of a patient. The graft prosthesis includes a purified, collagen-based matrix structure removed from a submucosa tissue source. The submucosa tissue source is purified by disinfection and removal steps to deactivate and remove contaminants, thereby making the purified structure biocompatible and suitable for grafting on and/or in a patient.

What is claimed is:  
     
         1 . A graft prosthesis comprising: 
 a purified, collagen-based matrix structure removed from a submucosa tissue source, said purified structure having a contaminant level making said purified structure biocompatible.    
     
     
         2 . The graft prosthesis of  claim 1 , wherein said purified structure has an endotoxin level of less than 12 endotoxin units per gram.  
     
     
         3 . The graft prosthesis of  claim 2 , wherein said endotoxin level is less than 10 endotoxin units per gram.  
     
     
         4 . The graft prosthesis of  claim 3 , wherein said endotoxin level is less than 5 endotoxin units per gram.  
     
     
         5 . The graft prosthesis of  claim 4 , wherein said endotoxin level is less than 1 endotoxin unit per gram.  
     
     
         6 . The graft prosthesis of  claim 1 , wherein said purified structure has a bioburden level of less than 2 colony forming units per gram.  
     
     
         7 . The graft prosthesis of  claim 6 , wherein said bioburden level is less than 1 colony forming unit per gram.  
     
     
         8 . The graft prosthesis of  claim 7 , wherein said bioburden level is less than 0.5 colony forming units per gram.  
     
     
         9 . The graft prosthesis of  claim 1 , wherein said purified structure has a nucleic acid content level of less than 10 micrograms per milligram.  
     
     
         10 . The graft prosthesis of  claim 9 , wherein said nucleic acid content is less than 2 micrograms per milligram.  
     
     
         11 . The graft prosthesis of  claim 1 , wherein said purified structure has a virus level of less than 500 plaque forming units per gram.  
     
     
         12 . The graft prosthesis of  claim 11 , wherein said virus level is less than 100 plaque forming units per gram.  
     
     
         13 . The graft prosthesis of  claim 12 , wherein said virus level is less than 1 plaque forming unit per gram.  
     
     
         14 . The graft prosthesis of claim, wherein said purified structure has a processing agent level of less than 100,000 parts per million per kilogram.  
     
     
         15 . The graft prosthesis of  claim 14 , wherein said processing agent level is less than 1,000 parts per million per kilogram.  
     
     
         16 . The graft prosthesis of  claim 15 , wherein said processing agent level is less than 100 parts per million per kilogram.  
     
     
         17 . The graft prosthesis of  claim 1 , wherein said purified structure has a fungus level of less than 2 colony forming units per gram.  
     
     
         18 . The graft prosthesis of  claim 17 , wherein said fungus level is less than 1 colony forming units per gram.  
     
     
         19 . The graft prosthesis of  claim 18 , wherein said fungus level is less than 0.5 colony forming units per gram.  
     
     
         20 . The graft prosthesis of  claim 1 , wherein said purified structure comprises a delaminated submucosa tissue source.  
     
     
         21 . The graft prosthesis of  claim 1 , wherein said purified structure comprises a disinfected and delaminated submucosa tissue source.  
     
     
         22 . The graft prosthesis of  claim 1 , wherein said purified structure comprises a disinfected and then delaminated submucosa tissue source.  
     
     
         23 . A graft prosthesis comprising: 
 a purified, collagen-based matrix structure removed from a submucosa tissue source, said purified structure having an endotoxin level of less than 12 endotoxin units per gram.    
     
     
         24 . A graft prosthesis comprising: 
 a purified, collagen-based matrix structure removed from a submucosa tissue source, said purified structure having a nucleic acid content level of less than 2 micrograms per milligram.    
     
     
         25 . A graft prosthesis comprising: 
 a purified, collagen-based matrix structure removed from a submucosa tissue source, said purified structure having a virus level of less than 500 plaque forming units per gram.    
     
     
         26 . A graft prosthesis comprising: 
 a purified, collagen-based matrix structure removed from a submucosa tissue source, said purified structure having a processing agent level of less than 100,000 parts per million per kilogram.    
     
     
         27 . A method for obtaining a collagen-based matrix from a submucosa tissue source, comprising: 
 treating the submucosa tissue source with a disinfecting agent to provide a disinfected submucosa tissue source; and    removing the collagen-based matrix from the disinfected submucosa tissue source.    
     
     
         28 . The method of  claim 27 , wherein the submucosa tissue source is from an alimentary tract of a mammal.  
     
     
         29 . The method of  claim 28 , wherein the mammal is a pig.  
     
     
         30 . The method of  claim 29 , wherein the submucosa tissue source is from the small intestine of a pig.  
     
     
         31 . The method of  claim 27 , wherein the disinfecting agent is an oxidizing agent.  
     
     
         32 . The method of  claim 27 , wherein the disinfecting agent is a peroxy compound.  
     
     
         33 . The method of  claim 32 , wherein the disinfecting agent is an organic peroxy compound.  
     
     
         34 . The method of  claim 33 , wherein the disinfecting agent is a peracid.  
     
     
         35 . The method of  claim 34 , wherein the peracid is selected from the group consisting of peracetic acid, perpropionic acid and perbenzoic acid.  
     
     
         36 . The method of  claim 35 , wherein the peracid is peracetic acid.  
     
     
         37 . The method of  claim 34 , wherein said treating includes treating the submucosa tissue source with a medium containing an alcohol and the peracid.  
     
     
         38 . The method of  claim 37 , wherein the alcohol has one to about six carbon atoms.  
     
     
         39 . The method of  claim 38 , wherein the alcohol is selected from the group consisting of ethanol, propanols, and butanols.  
     
     
         40 . The method of  claim 39 , wherein the alcohol is ethanol.  
     
     
         41 . The method of  claim 40 , wherein the medium is an aqueous ethanol solution containing from about 0.1% to about 0.3% by volume peracetic acid.  
     
     
         42 . The method of  claim 34 , wherein said treating includes treating the submucosa tissue source with a medium containing the peracid and having a pH of about 2 to about 6.  
     
     
         43 . The method of  claim 42 , wherein the medium has a pH of about 2 to about 4.  
     
     
         44 . The method of  claim 43 , wherein the peracid is peracetic acid, and the medium contains about 0.1% to about 0.3% by volume of peracetic acid.  
     
     
         45 . A method for obtaining a collagen-based matrix from a submucosa tissue source, comprising: 
 providing a submucosa tissue source which has been treated with a disinfecting agent; and    removing the collagen-based matrix from said submucosa tissue source.    
     
     
         46 . The method of  claim 45 , wherein said submucosa tissue source is from a small intestine.  
     
     
         47 . The method of  claim 46 , wherein said disinfecting includes treating the submucosa tissue source with an oxidizing agent.  
     
     
         48 . The method of  claim 47 , wherein said treating includes contacting the submucosa tissue source with an aqueous medium containing the oxidizing agent.  
     
     
         49 . The method of  claim 47 , wherein said treating includes contacting the submucosa tissue source with an aqueous medium containing a peroxy compound.  
     
     
         50 . The method of  claim 49 , wherein the peroxy compound is a peracid.  
     
     
         51 . The method of  claim 50 , wherein the peracid is peracetic acid.  
     
     
         52 . The process of  claim 51 , wherein the medium comprises an alcohol.  
     
     
         53 . The process of  claim 52 , wherein the alcohol is ethanol.  
     
     
         54 . The method of  claim 51 , wherein the small intestine is from a pig.  
     
     
         55 . A composition comprising: 
 a collagen-containing structure removed from a tissue source initially containing said structure and other tissue, said collagen-containing structure having an endotoxin level of no greater than 12 endotoxin units per gram.    
     
     
         56 . The composition of  claim 55 , wherein said collagen-containing layer is submucosa and said tissue source is small intestine.  
     
     
         57 . The composition of  claim 56 , wherein said tissue source is pig small intestine.  
     
     
         58 . The composition of  claim 55 , wherein said endotoxin level is less than 10 endotoxin units per gram.  
     
     
         59 . The composition of  claim 58 , wherein said endotoxin level is less than 5 endotoxin units per gram.  
     
     
         60 . The composition of  claim 50 , wherein said endotoxin level is less than 1 endotoxin unit per gram.  
     
     
         61 . The composition of  claim 60 , wherein said endotoxin level is less than 0.5 endotoxin units per gram.  
     
     
         62 . A purified collagen-containing matrix obtained from a mammalian tissue source, said matrix comprising mammalian tela submucosa and residual contaminants from said mammalian tissue source, said structure obtainable by a process which comprises disinfecting said mammalian tissue and then removing said structure from the disinfected mammalian tissue.  
     
     
         63 . The composition of  claim 62  wherein said disinfecting includes contacting the mammalian tissue source with an aqueous solution containing a peracid.