Impurity of thrombin preparations for clinical use.
Recent advances in the treatment of upper gastro-intestinal bleeding has led to the use of thrombin preparations in this condition. In the present investigation, the purity of thrombin preparations from one American pharmaceutical company and two Japanese pharmaceutical companies was examined using immunological and biological methods. An SDS-PAGE study revealed that each preparation contained various proteins other than thrombin. An immunological study revealed that each of the thrombin preparations contained proteins which were of at least two types. The thrombin preparations exhibited various biological activities other than thrombin activity, and their activities were widely different. Preparation A showed the strongest activity among the three, in terms of amidolytic activity, gamma-gamma dimer production rate, fibrin production rate, release of fibrinopeptide A, and anti-stretch activity. However, preparation A revealed the strongest binding activity to antithrombin III. Preparation B had the least contamination while preparation C showed the highest activity in terms of fibrinolytic and platelet-aggregating activity. Thus, each thrombin preparation had a greater or lesser degree of impurity, and it would appear that purer preparations are required for local administration in the treatment of upper gastro-intestinal bleeding.
D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation / Q000187:drug effects; D004340:Drug Contamination; D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005344:Fibrinopeptide A / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000032:analysis* / Q000627:therapeutic use; D013997:Time Factors
D005344:Fibrinopeptide A; D000990:Antithrombin III; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin