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.

Inactive Publication Date: 2019-02-12
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +3
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although the application of recombinant or plasma-derived FVIII / FIX can effectively treat hemophilia A and B, about 30% of patients develop antibodies after treatment, making the treatment ineffective

Method used

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  • Aprotinin or application of mutant, derivative and analogue or combination fragment thereof
  • Aprotinin or application of mutant, derivative and analogue or combination fragment thereof
  • Aprotinin or application of mutant, derivative and analogue or combination fragment thereof

Examples

Experimental program
Comparison scheme
Effect test

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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Abstract

The invention relates to aprotinin or application of a mutant, a derivative and an analogue or a combination fragment thereof. The aprotinin is used for preparing a medicine for treating related diseases or symptoms with acquired hemophilia and hemophilia with production of inhibitors. The aprotinin can be used for preparing the medicines for hemorrhagic diseases, especially related medicines forhemophilia with inhibitors, and the prospect is good.

Description

technical field [0001] The invention belongs to the field of hemorrhage treatment, and in particular relates to the application of aprotinin or its mutant, derivative, analog or its constituent fragments. Background technique [0002] Blood coagulation factor deficiency or other human coagulation disorders can lead to bleeding disorders, among which bleeding disorders caused by coagulation factor VIII / IX (FVIII / FIX) deficiency are called hemophilia (type A / B) In severe patients, the coagulation factor VIII / IX activity is often lower than 1% of normal, and spontaneous bleeding often occurs leading to muscle hematoma or joint deformity. Infusion of factor VIII / IX preparations (currently usually recombinantly expressed coagulation factor VIII / IX protein in vitro) to replenish the level of coagulation factor VIII / IX in patients is currently the only effective treatment, but frequent administration is required. Gene therapy is a treatment method currently undergoing clinical tri...

Claims

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Application Information

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IPC IPC(8): A61K38/55A61P7/04
CPCA61K38/55A61P7/04
Inventor 王学锋武文漫丁秋兰
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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