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Application of anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody

A hemophilia factor and monoclonal antibody technology, applied in the field of medicine, can solve problems such as severe bleeding, hindering the clinical application of drugs, and severe bleeding side effects

Inactive Publication Date: 2012-08-01
THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because abciximab also has the potential risk of causing severe bleeding, especially in Asian populations, bleeding side effects are more serious, and it has not been widely used in Asia, which hinders the clinical application of this type of drug to a certain extent

Method used

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  • Application of anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody
  • Application of anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody
  • Application of anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: animal grouping and design dosing regimen;

[0027] (1) Experimental animals

[0028] Yunnan Macaque (Suzhou Xishan Zhongke Experimental Animal Co., Ltd., experimental animal production license: SCXK (Su) 2007-0005; experimental animal use license: SYXK: (Su) 2006-0003. 2-3.5 years old, when the experiment started Weight 4.0-5.5Kg, 24, half male and half male.

[0029] (2) Dosing regimen

[0030] Macaque is negative control group (n=6) and administration group test (n=18), and administration group is divided into high dosage group (n=6), middle dosage group (n=6) and low dosage group (n=6) again. =6) Three groups, to study the effect of SZ-125 anti-arterial thrombosis drug in rhesus monkeys. The administration groups were divided into three groups of animals with high, middle and low doses, and the doses of macaques in each group were 0.6mg / Kg, 0.3mg / Kg and 0.1mg / Kg per kilogram of body weight respectively. The route of administration was aseptic intra...

Embodiment 2

[0033] Example 2: Effects of Changes in SZ-125 Cynomolgus Monkey Periodic Reductions in Blood Flow (CFRs)

[0034] After the rhesus monkey was anesthetized by intravenous injection of 3% pentobarbital sodium (30 mg / kg), the temperature of the animal was maintained at 37° C. on a heating platform. The femoral artery was carefully separated with a length of about 5 cm, and a soft silicone C-type peripheral vascular ultrasound probe with a diameter of 0.5 cm was wrapped around the proximal blood vessel. The average flow velocity of the femoral artery was continuously recorded during the experiment. After the macaque was stabilized for 30 minutes, three arterial clips with spring devices were used to completely block the blood flow for 20 seconds, and the interval between each arterial clip was 2 mm to damage the vessel wall. Place a hard self-made C-ring with an appropriate diameter in the middle of the injured vessel, and insert a 3.0mm diameter balloon catheter (Cordis, USA, 3...

Embodiment 3

[0036] Example 3: SZ-125 inhibits the binding of macaque plasma VWF to collagen in vivo

[0037] Coating plate: Dissolve human placenta type III collagen (product of Sigma Company) in coating buffer, and coat it on a multi-well ELISA plate at 20 μg / mL, 100 μL / well, overnight at 4°C in a humid box; the next day, use PBS-0.05% After washing with Tween 3 times, block with 200 μL / well of blocking solution, and store overnight in a humid box at 4°C; wash 3 times with PBS-0.05% Tween the next day, and then store for later use or freeze at -20°C.

[0038] Detection: add 0.38% sodium citrate anticoagulated plasma at each time point of the macaque plasma to be tested at each time point obtained in Example 1 before and after administration to each well of the above-mentioned coated type III collagen microplate, blank Add 2% BSA-PBS solution to the control well, and incubate at 37°C for 2 h; wash with PBS-0.05% Tween for 3 times and add 1:4000 diluted horseradish peroxide-labeled rabbit ...

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Abstract

The invention relates to the field of medicine, which discloses the application of anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody in preparation of antithrombotic medicine. The anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody has the effect of obviously restraining periodic blood flow reduction (CFRs) in animal bodies, not only restrains the combination of blood plasma VWF and collagen, but also restrains human platelet aggregation induced by ristomycin. Moreover, the anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody has high affinity with the VWF, can keep the pharmacodynamic effect of antithrombosis in a macaque body within a wider time window, does not delay platelet count and bleeding time in the macaque body, does not affect the blood coagulation function, and has no haemorrhage side effects as antithrombotic medicine, wherein the anti-angiohemophilia factor A3 zone bifunctional monoclonal antibody adopts monoclonal antibody secreted by hybridoma cell strain SZ-125 with the preservation number of CGMCC NO.2501.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of bifunctional monoclonal antibodies against von Willebrand factor A3 region in the preparation of antithrombotic drugs. Background technique [0002] Thrombi refers to blood clots formed in human blood vessels. Thrombosis refers to the process of forming blood clots in blood vessels. Thrombosis is an important protection mechanism of the human body to prevent excessive blood overflow when individuals encounter trauma . The human body also has factors that inhibit the formation of thrombus to prevent the unlimited expansion of thrombus and abnormal thrombus formation, that is, the anticoagulation system. After the thrombus completes hemostasis, there is still a fibrinolytic mechanism to clear the thrombus in the body, and the fibrinolytic activator / fibrinolytic inhibitor mediates the fibrinolytic activity in the body. In this way, the two systems of hemostasis and antic...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P7/02
Inventor 赵益明阮长耿季顺东江淼
Owner THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIV
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