| Objectives:To study the short-term toxicity of the copolymer of HP 188 and HP 407 in mice,observe and evaluate the short-term toxicity of the copolymer of HP 188 and HP 407 in order to provide basis for the safe and reasonable clinical medication.Methods : Part I: Prepare the material,using poloxamer 188,poloxamer 407 and ordinary heparin sodium to synthesize the copolymer of HP with the method of EDC / NHS.The characterization of those two kinds of copolymers could be detected by the mothods of infrared spectroscopy and magnetic resonance spectroscopy.The content of heparin in the copolymer could be determined by the method of toluidine blue staining,which determines whether the material was successfully synthesized.Part II :To observe and evaluate the short-term toxicity of the two copolymer,we use the intraperitoneal injection of mice,the continuous administration and observation for 7 d.At the end of the trial,liver and kidney function,routine blood and pathologic changes of the relevant organs were also observed.Part III:Take the gradient concentration of heparin-poloxamer 407 gel in vitro hemolysis test to determine the drug hemolysis rate.Results:Part I:In this experiment,HP 188 and HP 407 were successfully synthesized.Part II:No difference amony the three groups neither in routine blood or pathologic changes of the relevant organs,but TBIL,CREATN and UA are different(P<0.05)compared to those of HP188 and normal.There are enlargement of glomerulus in HP188 group,not in normol and HP407 group.Part III :Hemolysis test: 0.5ml volume of heparin-poloxamer 407 gel hemolysis phenomenon,0.2ml and 0.1ml heparin-poloxamer 407 gel did not occur hemolysis phenomenon.Conclusions:The HP 188 is poisonous,By comparing the short-term toxicity with HP407 in mice,it is beneficial to the evaluation of toxicity of the two to provide basis for the reasonable medication in clinics.HP 407 may be more suitable for HP188 for vascular anastomosis of the thermo-sensitive materials. |
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