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DOI: 10.1055/s-1999-10842-4
Production of Human Albumin by Plasma Fractionation
Publication History
Publication Date:
28 April 2004 (online)
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Introduction
Human plasma is a complex mixture containing hundreds of proteins, peptides, lipids, sugars, salts etc. A number of plasma proteins like albumin, immunoglobulins, inhibitors and coagulation factors are of therapeutical value ([1], Tab. [1]). Because plasma as a raw material is too valuable to use a given batch for the production of one protein alone, there is a strong impetus to fractionate it. This allows the simultaneous production of multiple products of interest at any one time.
Plasma fractionation was pioneered by Cohn and his coworkers in the 1940s and early 1950s [2] [3]. The procedure, which was modified and improved by other groups [4] [5], utilizes the differences in solubility of plasma proteins in mixtures of ethanol and water whereby the pH of the plasma solution, its ionic strength and the working temperature are additional parameters influencing the fractionation.
Although today alternative methods are available, especially chromatographic techniques [6] [7] [8], most plasma is still fractionated by procedures based on the early works of Cohn. The main reasons are that ethanol fractionation procedures are perfectly validated and easily scaleable; that ethanol is inexpensive and easy to handle; that it inhibits bacterial growth under the working concentrations used and that it is easily removable by diafiltration and other methods [9].
At the beginning the only highly purified final product of Cohn‘s procedure and its variations was albumin which is the major plasma protein (Tab. [1]). Today, however, subsequent processing, improvements of Cohn‘s method plus the integration of chromatographic steps make it possible to isolate and purify simultanously a number of therapeutically important proteins from plasma, including those with extremely low concentrations. Examples are immunoglobulins, the coagulation factors VIII and IX, and inhibitors like antithrombin III.
References
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- 2 Cohn E J, Strong L E, Huges Jr W L, Mulford D J, Ashworth J N, Melin M, Taylor H L. Preparation and properties of serum and plasma proteins. IV. A system for the separation into fractions of the protein and lipo-protein components of biological tissues and fluids. J. Am. Chem. Soc.. 1946; 68 459-475
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- 8 Berglöf J H, Erikkson S E. Plasma fractionation by chromatography of albumin and IgG. In: Biotechnologie des proteines du plasma (Stoltz, J. F., Rivat, C., Eds.). Colloque INSERM. 1989; 175 201-206
- 9 Kistler P, Friedli H. Ethanol precipitation. In: Methods of plasma fractionation (Curling, J. M., Ed.). Academic Press, London - New York 1980: 3-15
- 10 Brummelhuis H G. Variables and control thereof in the preparation of plasma derivatives. In: Biotechnologie des proteins du plasma (Stoltz, J. F., Rivat, C., Eds.). Colloque INSERM. 1989; 175 9-17
- 11 Brunner K H. Plasma fractionation by means of continuous centrifugation. In: Biotechnologie des proteins du plasma (Stoltz, J. F., Rivat, C., Eds.). Colloque INSERM. 1989; 175 43-50
- 12 Fiore J V, Olson W P, Holst S L. Depth filtration. In: Methods of plasma fractionation (Curling, J. M., Ed.). Academic Press, London - New York 1980: 239-268
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