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사람 혈장으로부터 고순도 혈액응고 제 9인자의 산업적 생산
- Alternative Title
- Industrial-scale Production of High-purity Antihemophilic Factor IX from Human Plasma
- Author(s)
- Cho, Yong Woon
- Alternative Author(s)
- Yong Woon Choi
- Advisor
- 김용성
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2010-08
- Language
- eng
- Keyword
- Factor IX
- Alternative Abstract
- Human blood coagulation Factor IX is a glycoprotein that is indispensable for a coagulation cascade. The hemophilia B is caused by the absence or deficiency of the Factor IX due to a hereditary cause or a pathological cause. The hemophilia B is rare hereditary disease that primarily affects newborn male babies, affecting approximately one out of 30,000 ~ 50,000. The hemophilia B patient is treated by administering Factor IX concentrates purified from the human blood. Factor IX product is classified by purity; Factor IX complex (prothrombin complex concentrate containing vitamin K-dependent clotting factors) and high-purity Factor IX product. However, there were several findings reporting that administration of the Factor IX complex caused incidence of symptoms, such as venous thrombosis or disseminated intravascular coagulation (DIC). Such side reactions presumably result from hypercoagulable states caused by excessive amounts of coagulant proteins administered along with the Factor IX or unnecessary thrombogenic components in the concentrates. The most serious problem with blood-derived coagulation factors is the risk of viral infection due to plasma-derived viruses such as HIV, HAV, HBV, HCV and human parvovirus B19 contaminated in the blood. To ensure virus safety of the plasma-derived coagulation factors, virus inactivation and/or removal process is indispensable when we develop the manufacturing process. Green Cross Corp. has produced the Facnyne as a therapeutic product for hemophilia B patients since 1986. Also we introduced the solvent/detergent treatment which New York Blood Center developed as a virus inactivation method to manufacturing process of Factor IX complex in 1991. Because side effects of Factor IX complex may occur., higher purity and safer Factor IX product than Facnyne was required. Therefore, we developed the manufacturing process of GreenNine VF as a high-purity Factor IX product. To improve the purity of GreenNine VF, the purification processes such as heparin affinity column chromatography and cation exchange column chromatography were added to the manufacturing process of Facnyne. Also, to improve the virus safety of GreenNine VF, virus-retentive filtration process was introduced. All of the processes were optimized and scaled-up to industrial production scale. The GreenNine VF products obtained from industrial-scale production have shown to be of higher purity and viral safety. The specific activity of GreenNine VF was 190.8 IU/mg which exceeded that in Facnyne. GreenNine VF was shown to have the highest purity in comparison with commercially available high purity factor IX products; Mononine(CSL), Octanyne(Octapharma), Berinine HS(Behringwerke), and Immunine STIM plus 600 (Baxter). One lot size of the production was 2,400 vials of 250 IU drug product or 1,200 vials of 500 IU drug product from 1,600 L cryo-poor plasma.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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