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Developing a Highly Active Blood Anticoagulant-a Heparin Complex with Glutamic Acid-by Simulating Chemical Equilibria Based on pH-Metric Data

机译:通过基于PH-度量数据模拟化学均衡,开发高活性血液抗凝血剂 - 肝素复合物 - 通过模拟化学平衡

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The anticoagulant activity of high-molecular-weight heparin is increased by developing a new highly active heparin complex with glutamate using the thermodynamic model of chemical equilibria based on pH-metric data. The anticoagulant activity of the developed complexes is estimated in the pH range of blood plasma according to the drop in the calculated equilibrium Ca2+ concentration associated with the formation of mixed ligand complexes of Ca2+ ions, heparin (Na(4)hep), and glutamate (H(2)Glu). A thermodynamic model is calculated by mathematically modelling chemical equilibria in the CaCl2-Na(4)hep-H(2)Glu-H2O-NaCl system in the pH range of 2.30 aecurrency pH aecurrency 10.50 in diluted saline that acts as a background electrolyte (0.154 De NaCl) at 37A degrees C and initial concentrations of the main components of nu x 10(-3) M, where n aecurrency 4. The thermodynamic model is used to determine the main complex of the monomeric unit of heparin with glutamate (HhepGlu(5-)) and the most stable mixed ligand complex of Ca2+ with heparin and glutamate (Ca(2)hepGlu(2-)) in the pH range of blood plasma (6.80 aecurrency NEuroDe aecurrency 7.40). It is concluded that the Ca(2)hepGlu(2-) complex reduces the Ca2+ concentration 107 times more than the Ca2+ complex with pure heparin. The anticoagulant effect of the developed HhepGlu(5-) complex is confirmed in vitro and in vivo via coagulation tests on the blood plasma of laboratory rats. Additional antithrombotic properties of the developed complex are identified. The new highly active anticoagulant, HhepGlu(5-) complex with additional antithrombotic properties, is patented.
机译:通过使用基于pH度量数据的化学均衡的热力学模型,通过使用谷氨酸的新高活性肝素复合物进行高分子重量肝素的抗凝血活性。根据Ca2 +离子的混合配体复合物,肝素(Na(4)Hep)和谷氨酸(Na(4)术(4)所述h(2)glu)。通过在2.30 AE&的pH范围内的CaCl2-Na(4)Hep-H(2)Glu-H2O-NaCl系统中的数学建模化学均衡来计算热力学模型。 pH AE&货币& 10.50在稀释的盐水中,用作37A℃的后台电解质(0.154 de NaCl)和Nu×10(-3)m的主要成分的初始浓度,其中N AE& 4.热力学模型用于确定肝素单体单元的主要复合物,用谷氨酸(Hhepglu(5-))和Ca2 +的最稳定的混合配体络合物与肝素和谷氨酸(Ca(2)hepglu(2-) )在pH范围的血液血浆(6.80 AE& Currency&神经态AE& Mocurence& 7.40)。结论是Ca(2)Hepglu(2-)复合物将Ca2 +浓度降低107倍,比Ca2 +复合物与纯肝素相比。发育的Hhepglu(5-)络合物的抗凝血效果在体外和体内通过实验室大鼠血浆的凝固试验来证实。鉴定了发育复合物的额外抗血栓形成性质。新的高活性抗凝血剂Hhepglu(5-)复合物具有额外的抗血栓形成,是专利的专利。

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