Research On The PEGylation Of Recombinant Human Growth Hormone

The human growth hormone (hGH) is a protein of synthesized andsecreted from the anterior lope of the pituitary gland, has 191 amino residuesand a molecular weight of 22kDa. It is the treatment for severe growthretardation resulting from growth hormone deficiency in clinical for childrenand adults.A drawback to therapy however ,is the short serum half-life and rapidclearance of hGH protein in vivo, therefore, to maintain an effective drugconcentration ,must be daily subcutaneous injection. This results in a treatmentregimen that places a significant burden on the patient and impacts on thequality of life and decreases compliance of patient, increases cost of treatment.In order to overcome the above problems, we have developed the methodwhich a 40kDa monomethoxypolyethylene glycol polymer covalently attachedto the rhGH protein, by increasing molecular weight of rhGH, decreases rateof clearance of renal, prolongs its half-life in vivo, so that decreases injectionfrequency.First, by adjusting molar ratio of PEG and rhGH, and controlling otherreactive condition, for example, reactive pH, temperature, reactive time andpurification procedure, it was possible to isolate hGH derivatives containingone PEG moiety, and conjugation efficiency is above 40%, in the conjugatedmixture, derivative which consistent with one 40kDa PEG to one rhGH isabove 90%.At the same time, we have found that increasing concentration ofrhGH protein and molar ratio of PEG to rhGH is significant approach whichincreasing reaction efficiency. In addition, to obtain one PEG to one rhGH...