Aprotinin or application of mutant, derivative and analogue or combination fragment thereof
An aprotinin and derivative technology, which is applied in the application of aprotinin or its mutants, analogs or its constituent fragments, and derivatives, can solve problems such as treatment failure, and achieve the effect of improving blood coagulation function.
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Embodiment 1
[0025] Aprotinin Corrects Thrombin Generation Defects in Hemophilia A, B Plasma and Hemophilia A Patients with Inhibitors
[0026] Thrombin generation test (TGT): It is a comprehensive experiment used to monitor the ability of thrombin generation in plasma. The activator (including tissue factor and phospholipid) is added to the blood plasma to start the coagulation reaction, and then the specific fluorescent substrate of thrombin is added, and the generated thrombin catalyzes the substrate to release the fluorescent group, and the generated thrombin is dynamically monitored by the FLUOROSKAN fluorescence reader. Fluorescent signal, use the supporting thrombin generation experiment software to convert the signal into a thrombin generation curve. The ability to generate thrombin is mainly evaluated by several parameters of the curve: (1) lag time (lag time), that is, the time required from the beginning of the reaction to the generation of thrombin; (3) time to peak (ttpeak), ...
Embodiment 2
[0029] Aprotinin promotes hemostasis after tail docking in hemophilic mice
[0030] (1) Inject aprotinin into type A hemophilia mice. Hemophilia mice aged 4-8 weeks were selected, and aprotinin (plasma concentration 15uM, or 30uM) physiological saline was injected into 6-7 mice respectively through the tail vein. Injection of coagulation factor VIII (normal plasma concentration 50% or 100%) was used as positive control; PBS injection of 6 mice was used as negative control.
[0031] (2) After the mice were anesthetized, the tail was docked at a place with a diameter of 2 mm, and the tail was immersed in PBS, and the timing was started immediately for 10 minutes, and then the hemoglobin was detected, and the degree of bleeding was estimated according to the amount of hemoglobin (see image 3 ). Depend on image 3 It can be seen that aprotinin can correct the coagulation defect caused by the deficiency of blood coagulation factor VIII in vivo, and reduce bleeding, wherein 30uM...
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