Modified collagen

Abstract

The present invention relates to a modified collagen obtainable by providing isolated collagen; freezing the isolated collagen; dehydrating the frozen collagen; and maturing the dehydrated collagen. Also disclosed are methods of preparing the modified collagen and uses thereof.

1 . A method for preparing a modified collagen, the method comprising the steps of:
 (a) providing isolated collagen;   (b) freezing the isolated collagen; and   (c) dehydrating the frozen collagen.   
     
     
         2 . A method according to  claim 1 , further comprising the step of (d) maturing the dehydrated collagen. 
     
     
         3 . A method according to  claim 1  or  2 , wherein the providing step comprises the step of removing the fluid prior to the providing step to provide a dispersion having a concentration of about 3-30% (w/w) collagen particles. 
     
     
         4 . A method according to any one of  claims 1 - 3 , wherein the freezing step comprises freezing to a temperature of about −33° C. to about −42° C. 
     
     
         5 . A method according to any one of  claims 1 - 4 , wherein the dehydrating step comprises removing the aqueous phase by reducing the pressure to about 0.05 to about 0.5 mbar. 
     
     
         6 . A method according to any one of  claims 1 - 5 , wherein the dehydrating step comprises increasing the temperature of the collagen to about +30° C. 
     
     
         7 . A method according to any one of  claims 1 - 6 , wherein the dehydrating step comprises at least one equilibrating step, wherein the or each equilibrating step comprises maintaining the temperature at a constant temperature for at least 10 mins. 
     
     
         8 . A method according to  claim 7 , wherein the dehydrating step comprises six equilibrating steps, each equilibrating step being conducted when the temperature is increased by about 10° C. 
     
     
         9 . A method according to  claim 2 , wherein the maturing step comprises storing the dehydrated collagen at a temperature of at least 2° C. 
     
     
         10 . A method according to  claim 2  or  9 , wherein the maturing step is conducted for a period of at least one week. 
     
     
         11 . A method according to any one of  claim 2 ,  9 , or  10 , wherein the maturing step comprises storing the dehydrated collagen at a temperature of at least 2° C. for a period of at least six months. 
     
     
         12 . A method according to any one of  claim 2 ,  9 , or  10 , wherein the maturing step comprises storing the dehydrated collagen at a temperature of at least 30° C. for a period of at least two months. 
     
     
         13 . A method according to any one of  claim 2 ,  9 , or  10 , wherein the maturing step comprises storing the dehydrated collagen at a temperature of at least 40° C. for a period of at least six weeks. 
     
     
         14 . A method according to any one of  claim 2 ,  9 , or  10 , wherein the maturing step comprises storing the dehydrated collagen at a temperature of at least 65° C. for a period of at least one week. 
     
     
         15 . A method according to any one of  claim 2  or  9 - 14 , wherein the maturing step is conducted at a relative humidity of less than 80%. 
     
     
         16 . A modified collagen obtainable by providing isolated collagen; freezing the isolated collagen; dehydrating the frozen collagen; and maturing the dehydrated collagen. 
     
     
         17 . A composition comprising a modified collagen according to  claim 16 , or a modified collagen prepared according to any one of  claims 1 - 15 , for use in treating or preventing surgical adhesions. 
     
     
         18 . A composition for use according to  claim 17 , wherein use comprises the administration of the composition at a biological membrane. 
     
     
         19 . A method for the manufacture of a composition comprising a modified collagen according to  claim 16  or a modified collagen prepared according to any one of  claims 1 - 15 , the method comprising the steps of:
 (a) providing the modified collagen; 
 (b) preparing an aqueous dispersion of the modified collagen; 
 (c) degrading the aqueous dispersion; and 
 (d) dehydrating the aqueous dispersion. 
 
     
     
         20 . A method according to  claim 19 , wherein the preparing step comprises adding water heated to about 35 to about 42° C. to the modified collagen, prior to adding to the modified collagen. 
     
     
         21 . A method of preparing a drug delivery composition for sustained drug release, the method comprising the steps of:
 (a) providing isolated collagen;   (b) freezing the isolated collagen; and   (c) dehydrating the frozen collagen.   
     
     
         22 . A method according to  claim 21 , further comprising the step of (d) maturing the dehydrated collagen. 
     
     
         23 . A method according to  claim 21  or  22 , further comprising the step of providing a drug to which the matured collagen is added, or which is added to the matured collagen. 
     
     
         24 . A method according to  claim 23 , wherein the drug is selected from gentamicin ((3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,6S)-3-amino-6-[(1R)-1-(methylamino)ethyl]oxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-5-methyl-4-(methylamino)oxane-3,5-diol), or a salt or prodrug thereof, and bupivacaine ((RS)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide), or a salt or prodrug thereof. 
     
     
         25 . A method according to  claim 23  or  24 , further comprising the step of lyophilizing and/or dehydrating, the drug-containing drug delivery composition. 
     
     
         26 . A drug delivery composition obtainable by providing isolated collagen; freezing the isolated collagen; dehydrating the frozen collagen; and maturing the dehydrated collagen.