Stable thrombin composition
The stable thrombin composition comprises purified thrombin, human albumin and a neutral salt, the resulting product being stable when stored as a lyophilisate or frozen and is adjusted to a nominal strength of 500 IU of thrombin or more per ml of solution, the human albumin being in a concentration of over 0.05% (w/v) and preferably between 0.1% (w/v) and 1% (w/v).
1 . A thrombin composition, characterised in that the composition comprises purified thrombin, human albumin and a neutral salt, the resulting product being stored either lyophilised or frozen.
2 . A thrombin composition according to claim 1 , characterised in that the thrombin is adjusted to a nominal strength of 500 IU of thrombin or more per ml of solution.
3 . A thrombin composition according to claim 1 , characterised in that the human albumin has a concentration of more than 0.05% (w/v) and preferably between 0.1% (w/v) and 1% (w/v).
4 . A thrombin composition according to claim 1 , characterised in that it includes the addition of a pH buffer.
5 . A thrombin composition according to claim 4 , characterised in that the pH buffer comprises glycine at a concentration of between 0.01 and 0.1 molar.
6 . A thrombin composition according to claim 4 , characterised in that the pH buffer comprises sodium citrate.
7 . A thrombin composition according to claim 4 , characterised in that the pH buffer comprises sodium acetate.
8 . A thrombin composition according to claim 1 , characterised in that it comprises calcium chloride or equivalent between 20 and 60 mM.
9 . A thrombin composition according to claim 1 , characterised in that the neutral salt is sodium chloride.
10 . A thrombin composition according to claim 9 , characterised in that the sodium chloride has a concentration of at least 0.05 molar.
11 . A thrombin composition according to claim 1 , characterised in that the solution can be filtered by double nanofiltration in series up to a nominal pore size of up to 35 nm and preferably 15 nm.
12 . A thrombin composition according to claim 11 , characterised in that up to 30 litres of solution may be filtered per m 2 of filtration area of each nanofilter.
13 . A thrombin composition according to claim 1 , characterised in that the lyophilised composition will stand dry heat treatment for ½ hour to 8 hours between 90 and 115° C., and preferably during 1-2 hours at 100° C.
14 . A process for the preparation of a thrombin composition, characterised in that the thrombin is purified to a specific activity of 1500 IU of thrombin/mg of protein or more and a strength of 500 IU of thrombin/ml or more, stabilising the solution through adding and mixing with human albumin and a neutral salt, subsequently applying a double nanofiltration system to the solution.
15 . A process according to claim 14 , characterised in that the nanofiltration is performed up to a nominal pore size of up to 35 nm.
16 . A process according to claim 15 , characterised in that the nanofiltration is carried out up to a pore size of 15 nm.
17 . A process according to claim 14 , characterised in that nanofiltration is carried out at between 5 and 30 litres of solution per square meter of filtration area for each nanofilter.
18 . A process according to claim 14 characterised in that the solution is subjected to a freezing process.
19 . A process according to claim 14 , characterised in that the solution is subjected to lyophilisation.
20 . A process according to claim 19 , characterised in that the lyophilised product is dry heat treated for a time of between half an hour and 8 hours at a temperature of between 90 and 115° C.
21 . A process according to claim 20 , characterised in that the lyophilised thrombin composition is dry heat treated for a time of 1-2 hours at 100° C.