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Urokinase (UK), a human urinary plasminogen activator, was modified chemically by a covalent attachment of methoxypolyethylene glycol (PEG) #5, 000 to its lysine residues after activation of PEG with cyanuric chloride. For the evaluation of thrombolytic activity of PEG-modified UK (PEG-UK), a novel experimental thrombosis model was developed in a dog's artery.The femoral artery of an anesthetized dog was exposed and transfusion catheter was fixed on its branch, and then the distal part was clamped at a distance of 2cm, washed with saline, and dried with oxygen to cause injury on intima. Thrombus was formed by an injection of both a fibrinogen solution and a thrombin solution into the clamped artery and thrombus formation was confirmed angiographically after removal of the clamps.Using this model, a strong thrombolytic activity of PEG-UK was shown by periodical angiographies when administered from the catheter. However, native UK couldn't dissolve the thrombus at a dose of 100, 000iu/dog. The serum FDP level of the PEG-UK reached to 1, 280μg/ml, while that of the native UK treated dog stayed at 20μg/ml.
- 一般社団法人 日本血栓止血学会の論文
一般社団法人 日本血栓止血学会 | 論文
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