Sterilization process

Abstract

The present invention relates to a process for sterilizing implantable biomaterials. In particular, the invention relates to a process for sterilizing collagen-containing implantable biomaterials and storage thereafter.

The claims defining the invention are as follows: 
     
         1 . A method for sterilizing a cross-linked collagen-based biomaterial comprising contacting said cross-linked collagen-based biomaterial with a sterilization solution comprising between 3% and 6% v/v propylene oxide and incubating said biomaterial between 30° C. and 55° C. for greater than 48 hours; with the proviso that the sterilization solution does not include alcohol. 
     
     
         2 . The method of  claim 1 , wherein the incubation temperature is between 35° C. and 50° C. 
     
     
         3 . The method of  claim 1 , wherein the incubation temperature is about 45° C. 
     
     
         4 . The method of  claim 1 , wherein the incubation temperature after 48 hours is reduced to room temperature. 
     
     
         5 . The method of  claim 1 , wherein the sterilization solution comprises between 3.8% and 4.5% v/v propylene oxide. 
     
     
         6 . The method of  claim 1 , wherein the sterilization solution comprises about 4% v/v propylene oxide. 
     
     
         7 . The method of  claim 1 , wherein the sterilization step is carried out for 2 to 10 days or more. 
     
     
         8 . The method of  claim 1 , wherein the collagen-based biomaterial is isolated from an animal selected from the group consisting of an ovine, a bovine, a caprine, an equine, a porcine, a marsupial and a human. 
     
     
         9 . The method of  claim 1 , wherein the biomaterial is a cellular tissue selected from the group consisting cardiovascular tissue, heart tissue, heart valve, aortic roots, aortic wall, aortic leaflets, pericardial tissue, connective tissue, dura mater, dermal tissue, a vascular tissue, cartilage, pericardium, ligament, tendon, blood vessels, umbilical tissue, bone tissue, fasciae, and submucosal tissue and skin. 
     
     
         10 . The method of  claim 9 , wherein the biomaterial further comprises synthetic analogs formed from synthetic polymers, biological polymers, or both. 
     
     
         11 . A method for sterilizing a collagen-based biomaterial comprising:
 (a) providing a collagen-based biomaterial and contacting with 0.625% v/v glutaraldehyde solution and potassium di-hydrogen phosphate pH 7.4;   (b) incubating said biomaterial at about 1-5° C. for at least 5 days to produce a cross-linked collagen-based biomaterial;   (c) contacting said cross-linked collagen-based biomaterial with a sterilization solution comprising between 3% and 6% v/v propylene oxide and incubating said biomaterial between 30° C. and 55° C. for greater than 48 hours; with the proviso that the sterilization solution does not include alcohol.   
     
     
         12 . A method of sterilizing and storing a cross-linked collagen-based biomaterial comprising contacting said cross-linked collagen-based biomaterial with a solution comprising between 3% and 6% v/v propylene oxide and incubating said biomaterial between 30° C. and 55° C. for greater than 48 hours and then allowing the biomaterial to remain in contact with said propylene oxide until same converts to propylene glycol; with the proviso that the solution does not include alcohol. 
     
     
         13 . A sterilized, cross-linked collagen-based biomaterial produced by the method of  claim 1 . 
     
     
         14 . A container comprising a sterilized, cross-linked collagen-based biomaterial and a 3% to 6% v/v propylene glycol solution, wherein said propylene glycol has resulted from the conversion in situ of a 3% to 6% v/v propylene oxide solution while in the presence of the biomaterial.