Study On Pharmacokinetics Of Recombinant Human CH-2 Modified With PEG

The thesis focuses on the development of PEG-rhCH-2, discusses the pharmacokinetics and concentration distribution in different tissues of PEG-rhCH-2. The essay is to master transformational rules of PEG-rhCH-2, and finally to provide important pharmacokinetics parameter for safe clinic drug using and for supplying bases and reference of proper using drug.Mice are used in the experiments with injection of rhCH-2 and PEG-rhCH-2. This essay discusses that polyethyleneglycol modification can influence pharmacokinetics parameter of rhCH-2 in the approach of Double antibody sandwich method, and from the aspect of blood concentration-time relation, and from the aspect of concentration distribution in different tissues.. The primary conclusions are the following.①Research of rhCH-2 antibody and rhCH-2 antibody marked with horseradish peroxidase (HRP), study on their formation, establishment of detected methods of rhCH-2's concentration in blood and distribution in different tissues by Double antibody sandwich ELISA.②Measure the different time's blood concentration-time curve after the injection of rhCH-2 and PEG-rhCH-2 of three doses (5μg/kg, 3μg/kg, and 1μg/kg) into mice. Apply method of compartment model to the pharmacokinetics parameter estimation of rhCH-2 and PEG-rhCH-2. And the results show that blood concentration-time curves of rhCH-2 and PEG-rhCH-2 are fitted to a two-compartment model. The t1/2βof rhCH-2 is 0.866±0.18h, PEG-rhCH-2 is 2.86±0.27h, which is three times of rhCH-2. The clearance (CL) is 0.416mL/h·kg , PEG-rhCH-2 is 0.492mL/h·kg. The volume of distribution (Vd) of rhCH-2 is estimated to be 9.81L/kg, PEG-rhCH-2 is 11.80L/kg. The results show polyethyleneglycol modification can obviously prolong CH-2's half-life period (t1/2).③By using enzyme linked immunosorbent assay methods, detect concentration distribution in heart, liver, kidney, spleen, bladder and stomach after the interjection of PEG-rhCH-2 5μg/kg into mice. The outcomes show that polyethyleneglycol's modification can distinctively heighten interferon omega's utilizing rate in different tissues, and with strong tissues pertinence. The results show that PEG-rhCH-2 spreads higher than rhCH-2 except in kidney, polyethyleneglycol modification can improve the using rate of rhCH-2 in different tissues.