Process for preparing human serum albumin

Abstract

The invention discloses a process for preparing human serum albumin. According to the process, a low-temperature ethanol separation method is adopted, and the human serum albumin is prepared from human plasma. The process comprises the steps of dissolving plasma; preparing an ingredient I; preparing an ingredient II and an ingredient III; preparing an ingredient IV; preparing an ingredient V; refining the ingredient V; carrying out ultrafiltration; diluting; carrying out pasteurization; sterilizing and packaging albumen; incubating products; and packaging finished products. The process has the advantages that solid-liquid separation is carried out by adopting a pressure filtration technology, so that the albumin yield which is higher than 29 g / L plasma is increased remarkably, the purity is higher than 98%, and the stability of the products is improved remarkably; Zetaplus deep filter-core filtration is combined with the prolongation of pasteurization time, so that the PKA (Protein Kinase A) level of the products is effectively controlled to be lower than 20IU / ml, and the risks of excessive heat source and virus infection in the products are reduced; and during the process, sodium chloride solutions of two gradient concentrations are used for carrying out ultrafiltration, so that not only can the ethanol residual quantity of the products be controlled to be lower than 0.025%, but also the aluminum residual quantity can be effectively minimized to be lower than 50 micrograms / L.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and relates to a process for separating and purifying protein drugs, in particular to a process for preparing human serum albumin. Background technique [0002] Human albumin is the main product of blood preparations and the final product of the backbone of the plasma protein production process. Albumin is synthesized very quickly in liver cells, and has the characteristics of relatively small molecule (molecular weight 66250), relatively large surface area, relatively symmetrical molecular configuration, simple structure, firmness, and high toughness. Albumin plays an important role in hemorrhagic shock, severe burns, cerebral edema, and hyperemia in liver and kidney diseases. Since Cohn et al. founded the low-temperature ethanol human plasma protein separation technology in the 1940s, the industrialized production of plasma proteins has made great progress. [0003] At present, mos...

AI Technical Summary

Problems solved by technology

[0003] At present, most of the manufacturers that produce human serum albumin by low-temperature ethanol separation method have low albumin yield, poor product stability, low purity, and other indicators are likely to fail to meet standards, such as PKA content, aluminum residue, polymer content, etc.

The main reason for the above shortcomings is the unreasonable preparation process

At present, most of the preparation processes use centrifugation to separate the components, and during the high-speed centrifugation process, due to the temperature rise of the centrifuge, some of the impurity proteins that should be precipitated are likely to dissolve and cannot be removed, leaving unstable factors

The high-speed centrifugation process of the two produces strong centrifugal shear force, which easily destroys the molecular structure of the protein, which will inevitably reduce the yield of albumin and affect the purity of the product.

[0005] In the existing albumin preparation process, there are all applications of ultrafiltration technology, but mainly using a single solution for dialysis, which can only well control the residual amount of ethanol within the required range, but cannot effectively reduce the residual amount of aluminum to a minimum. To ensure that the residual aluminum content of the product does not exceed the standard within the validity period