Method of making flexible bioresorbable hemostatic packing and stent having a preselectable in-vivo residence time

Abstract

The invention provides a method of making flexible bioresorbable foam having hemostatic properties and a preselectable in-vivo residence time. A blend of crosslinked collagen blended and a hyaluronic acid component is prepared. The blend is mixed with water to form a suspension. The blend is freezed and lyophilized at less than about 0° C. Next, the blend is crosslinked. The product is then sterilized and chain scission is performed by bombardment with gamma rays or a beam of electrons.

1 . A method of making a flexible bioresorbable foam having a preselectable in-vivo residence time comprising the steps of:
 preparing a blend consisting of collagen blended with an esterified hyaluronic acid component;   mixing the blend with water to form a suspension;   freezing and lyophilizing the suspension at less than about 0° C. to form a foam product;   crosslinking the foam product to form a crosslinked foam product;   bombarding the crosslinked foam product gamma rays or a beam of electrons to sterilize the crosslinked foam product; and   further bombarding the crosslinked foam product with gamma rays of a beam of electrons to cause chain scission and provide the crosslinked foam product with a preselected in-vivo residence time of between about 5 days and about 14 days.   
     
     
         2 . The method of making flexible bioresorbable foam of  claim 1 , wherein the lyophilization is performed at a temperature of less than about −40° C. 
     
     
         3 . The method of making flexible bioresorbable foam of  claim 1 , wherein the crosslinking is achieved by means of a method selected from dehydrothermal crosslinking and chemical crosslinking. 
     
     
         4 . The method of making flexible bioresorbable foam of  claim 1 , wherein crosslinking is achieved by use of formaldehyde vapor. 
     
     
         5 . The method of making flexible bioresorbable foam of  claim 4 , wherein the formaldehyde vapor is evacuated after a period of between about 2 hours and about 7 hours. 
     
     
         6 . The method of making flexible bioresorbable foam of  claim 1 , wherein the blend comprises between about 70 percent and about 90 percent by weight of the esterified hyaluronic acid component. 
     
     
         7 . The method of making flexible bioresorbable foam of  claim 1 , wherein the esterified hyaluronic acid has an esterification level of between about 60 percent and about 70 percent. 
     
     
         8 . The method of making flexible bioresorbable foam of  claim 1 , wherein the esterified hyaluronic acid is selected from the group consisting of a benzyl ester of hyaluronic acid, an ethyl ester of hyaluronic acid and mixtures thereof. 
     
     
         9 . The method of making flexible bioresorbable foam of  claim 1 , wherein the crosslinked collagen is a microfibrillar collagen. 
     
     
         10 . A method of making a flexible bioresorbable foam having a preselectable in-vivo residence time, wherein the method comprises the steps of:
 preparing a blend consisting of collagen blended with an esterified hyaluronic acid component;   mixing the blend with water to form a mixture;   freezing the mixture;   lyophilizing the mixture;   crosslinking the mixture to form a crosslinked product;   sterilizing the crosslinked product; and   causing chain scission on the crosslinked product to provide the crosslinked product with a preselected in-vivo residence time of between about 5 days and about 14 days.   
     
     
         11 . The method of making flexible bioresorbable foam of  claim 10 , wherein crosslinking is achieved using formaldehyde vapor. 
     
     
         12 . The method of making flexible bioresorbable foam of  claim 11 , wherein the formaldehyde vapor is evacuated after a period of between about 2 hours and about 7 hours. 
     
     
         13 . The method of making flexible bioresorbable foam of  claim 10 , wherein the blend comprises between about 70 percent and about 90 percent by weight of the esterified hyaluronic acid component. 
     
     
         14 . The method of making flexible bioresorbable foam composition of  claim 10 , wherein the step of sterilizing is performed by bombardment with gamma rays. 
     
     
         15 . The method of making flexible bioresorbable foam of  claim 10 , wherein the esterified hyaluronic acid has an esterification level of between about 60 percent and about 70 percent. 
     
     
         16 . The method of making flexible bioresorbable foam of  claim 10 , wherein the esterified hyaluronic acid is selected from the group consisting of a benzyl ester of hyaluronic acid, an ethyl ester of hyaluronic acid and mixtures thereof. 
     
     
         17 . The method of making flexible bioresorbable foam of  claim 10 , wherein the crosslinked collagen is a microfibrillar collagen.