Studies on the pilot of recombinant streptokinase

Streptokinase (SK) acts as a specific effective medicine for thrombolytic therapy of acute myocardial infarction (AMI). Because of the inscufficient yields obtained in normal SK production and the pathogenicity of its natural host, it was worthwhile to search for a recombinant source of SK, with a high yield of production and a safe technological procedure. The strategy for pilot and industrial production of recombinant streptokinase (r-SK) was presented: by using 20L BIOFLO IV fermentor, the recombinant bacteria were ampilified in 30°C first, and then introduced in 42°C for more than 2 h, as a result as a 25 g/L of culture density and a high expression level of r-SK, which was up to 78% of total bacteria proteins. Having been renatured with guanidine hydrochloride liner dilution and purified from gel filtration and ion-exchange chromotography, the final products reached 100000IU/mg of specific activity and 98% of purity. Each pilot yielded 9 g r-SK, which is equal to 600 doses of clinical use in the treatment of AMI. It was confirmed that the r-SK products was not only specific effective but also highly safe for thrombolytic therapy, with the results of the pre-clinical investigation. Also, it was supported by the statistics of the clinical trial investigation that r-SK has the efficiency of the complete lysis in r-SK-treat patients, up to 80%, as the same as the native SK, but a less incidence of complications.