| Tumor blood vessels is the source of tumorigenesis,oxygen and nutrition development,targeting tumor angiogenesis can inhibit tumor growth.Vascular endothelial growth factor(VEGF)is a kind of factor that can regulate angiogenesis,they play a biological effect after combined with their receptor,VEGFR2 is the key receptor of the VEGF angiogenic signals transduction,participate in regulating the VEGF pathway mediated cell proliferation,cell survival,migration and angiogenesis.And VEGFR2 not only expressed on endothelial cells related with tumor,and may also in some tumor cells,especially on cancer stem cells are also high expression,so the selective blocking VEGFR2 signaling pathways can inhibit the growth of tumor cells and the formation of tumor blood vessels.Recombinant humanized monoclonal antibody is a kind of selective blocking VEGFR2 signaling pathways,it is a kind of immunoglobulin.Protein traits,and can inhibit the growth of tumor cells and the formation of tumor blood vessels.The protein is not stable,easy deactivation.The better quality of monoclonal antibody injection must have a better prescription.At the same time,in order to ensure the clinical dosage need research the filling volume,this article is based on appearance,concentration,pH value,osmotic pressure,the A350,SEC-HPLC,CEX-HPL experiment analysis,extract more stable prescription and confirm the product filling volume,the main content are as follows:(1)The buffer system screening study Discusses the three groups of different buffer system,take adequate DS to concentrate ultrafiltration in liquid,add materials,adjust the concentration then aseptic filling to 10 mL penicillin vials,add the 20 mm stopper,cap the 20 mm aluminum cap.Place the samples filled in 40 ± 2 ℃ and 2～8 ℃ constant temperature medicinal preservation box,reserve eight weeks,in 0,1,2,4,8 weeks respectively sampling,finally,select the most stable prescription by means of physical and chemical related experimental results,thereby produce the better stability recombinant humanized anti-VEGFR2 monoclonal antibody injection.(2)The materials of screening study According to the research results of the buffer system screening study,we choose the 20 mM pH 6.0 sodium dihydrogen phosphate-sodium citrate as the final buffer system for the products.Screening materials include sucrose,sorbitol,mannitol,sodium chloride and Tween 80.Take adequate DS to concentrate ultrafiltration in liquid,add materials,adjust the concentration then aseptic filling to 10 mL penicillin vials,add the 20 mm stopper,cap the 20 mm aluminum cap.Place the samples filled in 40 ± 2 ℃ and 2～8 ℃ constant temperature medicinal preservation box,reserve eight weeks,in 0,1,2,4,8 weeks respectively sampling,finally,select the most stable prescription by means of physical and chemical related experimental results,thereby produce the better stability recombinant humanized anti-VEGFR2 monoclonal antibody injection..(3)Filling volume study Recombinant humanized anti-VEGFR2 monoclonal antibody protein is similar biological medicine,it is biological products class 1 new drug for treatment.Pharmacopoeia require to increase the appropriate filling volume considering the loss of residues on the stoppers and vials of wall.As well as the injector loss including needle remain and the injector adhesive,it is impossible that there is no remain in injector needle,BP and USP requires to remove the bubbles and keep the needle remain.Through simulated patients dosing process,to confirm the products filling volume range in accordance with the filling volume study make the dosing volume is not less than 10.0 mL for ensuring the clinical dosage.According to the GMP requirements,to study and analysis optimization of formulation and filling volume for producing the better stability recombinant humanized anti-VEGFR2 monoclonal antibody injection.. |
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