Freeze-dried composite materials

Abstract

The invention provides a sterile freeze-dried sponge, wherein at least 80% by weight of the sponge consists of collagen and oxidized regenerated cellulose in the weight ratio 60:40 to 40:60, wherein the sponge has a dry tensile strength of more than 3N and/or a wet tensile strength of more than 1 N. Preferably, the collagen has a degree of denaturation less than 20% and the sponge is substantially free of chemical cross-links. The invention also provides methods for the manufacture of sponges according to the invention

1 . A sterile freeze-dried sponge, wherein at least 80% by weight of the sponge consists of a mixture of collagen and oxidized regenerated cellulose in the weight ratio 60:40 to 40:60, and wherein the sponge has a dry tensile strength as herein defined of more than 3N.  
     
     
         2 . A sterile freeze-dried sponge, wherein at least 80% by weight of the sponge consists of a mixture of collagen and oxidized regenerated cellulose in the weight ratio 60:40 to 40:60, wherein the sponge has a wet tensile strength as herein defined greater than 1N.  
     
     
         3 . A sterile freeze-dried sponge according to    claim 1   , wherein the sponge is substantially free of chemical cross-links.  
     
     
         4 . A sterile freeze-dried sponge according to    claim 1   , wherein the collagen has a degree of denaturation less than 20%.  
     
     
         5 . A sterile freeze-dried sponge according to    claim 5   , wherein the collagen has a degree of denaturation less than 10%.  
     
     
         6 . A sterile freeze-dried sponge according to    claim 4   , wherein 80% of the oxidized regenerated cellulose fibers by volume are between 20 μm and 1000 μm in length.  
     
     
         7 . A sterile freeze-dried sponge according to    claim 6   , wherein the mean length of the oxidized regenerated cellulose fibers is from 250 to 450 μm.  
     
     
         8 . A sterile freeze-dried sponge according to    claim 1   , wherein the oxidized regenerated cellulose is in the form of fibers, and at least 90% of the fibers by volume are less than 1 mm in length.  
     
     
         9 . A sterile freeze-dried sponge according to    claim 1   , wherein the ratio of collagen to oxidized regenerated cellulose is from 50:50 to 55:45.  
     
     
         10 . A sterile freeze-dried sponge according to    claim 1   , wherein the bioburden (TVC) of the sponge is less than 100 cfu/g, preferably less than 10 cfu/g, more preferably less than 1 cfu/g.  
     
     
         11 . A sterile freeze-dried sponge according to    claim 1   , wherein the sponge contains from 5 to 15% by weight of water.  
     
     
         12 . A sterile freeze-dried sponge according to    claim 1   , wherein a layer of the sponge of thickness 3 mm has an uncompressed absorption capacity of 0.9% saline of from 15 to 20 g/100 cm 2 .  
     
     
         13 . A sterile freeze-dried sponge according to    claim 1   , wherein the sponge has a resorption time under simulated physiological conditions of more than 48 hours.  
     
     
         14 . A method of manufacture of a freeze-dried sponge pad comprising the steps of:—
 providing an acidified paste of purified collagen fibers, wherein the collagen is less than 10% denatured;  
 providing oxidized regenerated cellulose fibers, wherein at least 80% of said fibers have lengths in the range of 20 μm to 1000 μm;  
 combining said collagen and said ORC fibers in a homogeneous aqueous dispersion in a weight ratio of 60:40 to 40:60 collagen:ORC, said aqueous dispersion being acidified to a pH in the range of 2.8 to 3.2 and having a total solids concentration of 0.8 to 1.2% by weight;  
 pouring said aqueous dispersion into trays to a depth greater than 1 cm;  
 freezing the dispersion to a temperature below −30° C., followed by a temperature programmed freeze drying and dehydrothermal cross-linking to a final moisture content of 5-15% by weight;  
 splitting the freeze-dried dispersion to remove surface layers and leave one or more pads; and  
 sterilizing the one or more pads by gamma-irradiation.  
 
     
     
         15 . A method according to    claim 14    carried out substantially without the use of any chemical cross-linking agents.  
     
     
         16 . A method according to    claim 14   , wherein the step of providing collagen comprises the following steps:—
 providing fresh and unswollen splits of bovine corium;  
 treating the splits with a hypochloride solution to inhibit microbial activity;  
 treating the corium with a solution containing sodium hydroxide and hydrogen peroxide to swell and sterilize the corium; then  
 treating the corium with a aqueous alkali solution at a pH greater than 12 and temperature less than 50° C. for a period of ten-fourteen days; then  
 treating the corium with a aqueous acid solution at a pH of 0.8-1.2 and temperature less than 50° C.; then  
 washing the corium, and comminuting the corium with sufficient water to form a paste.  
 
     
     
         17 . A method according to    claim 14   , wherein the step of providing oxidized regenerated cellulose fibers comprising milling an oxidized regenerated cellulose cloth and screening the milled particles to remove particles having size less than 20 μm or greater than 1000 μm.  
     
     
         18 . A method according to    claim 14   , wherein the step of dispersing the collagen and the ORC comprises the steps of:—
 adding an acid-swollen collagen/water paste to acidified water;  
 adding oxidized regenerated cellulose fibers to the acidified water; and  
 homogenizing the resulting mixture.  
 
     
     
         19 . A method according to    claim 14   , wherein the step of freezing is carried out by placing the trays containing the aqueous dispersion onto chilled shelves in a freezer followed by holding the trays at a temperature below −30° C. until the freezing is complete.  
     
     
         20 . A method according to    claim 14   , wherein the step of freeze drying is carried out with dehydrothermal cross-linking.  
     
     
         21 . A method according to    claim 14   , wherein the step of sterilizing is carried out by gamma-irradiation at a dose of 18-29 KGy.  
     
     
         22 . A method according to    claim 14   , wherein the weight ratio of collagen to oxidized regenerated cellulose is from 50:50 to 55:45 and the pH of the aqueous dispersion is from 2.9 to 3.1.