Albumin, plasma heat stability

HSA is used therapeutically as an aqueous solution it is available in concentrated form (15-25 per cent protein) or as an isotonic solution (4-5 per cent protein). In both cases, in excess of 95 per cent of the protein present is albumin. It can be prepared by fractionation from normal plasma or serum, or purified from placentas. The source material must first be screened for the presence of indicator pathogens. After purification, a suitable stabilizer (often sodium caprylate) is added, but no preservative. The solution is then sterilized by filtration and aseptically filled into final sterile containers. The relative heat stability of HSA allows a measure of subsequent heat treatment, which further reduces the risk of accidental transmission of viable pathogens (particularly viruses). This treatment normally entails heating the product to 60 °C for 10 h. It is then normally incubated at 30-32 °C for a further 14 days and subsequently examined for any signs of microbial growth. 

The PhEur 2005 similarly describes albumin solution as an aqueous solution of protein obtained from human plasma see Section 13. It is available as a concentrated solution containing 150-250 g/L of total protein or as an isotonic solution containing 35-50 g/L of total protein. Not less than 95% of the total protein content is albumin. A suitable stabilizer against the effects of heat, such as sodium caprylate (sodium octanoate) or N-acetyltryptophan or a combination of these two at a suitable concentration, may be added, but no antimicrobial preservative is added. 

Inactivation and Removal of Viruses. In developing methods of plasma fractionation, the possibiHty of transmitting infection from human vimses present in the starting plasma pool has been recognized (4,5). Consequentiy, studies of product stabiHty encompass investigation of heat treatment of products in both solution (100) and dried (101) states to estabHsh vimcidal procedures that could be appHed to the final product. Salts of fatty acid anions, such as sodium caprylate [1984-06-17, and the acetyl derivative of the amino acid tryptophan, sodium acetyl-tryptophanate [87-32-17, are capable of stabilizing albumin solutions to 60°C for 10 hours (100) this procedure prevents the transmission of viral hepatitis (102,103). The degree of protein stabilization obtained (104) and the safety of the product in clinical practice have been confirmed (105,106). The procedure has also been shown to inactivate the human immunodeficiency vims (HIV) (107). 

Factors Affecting Stability to Heat Plasma and serum are notable for their capacity to hold in stable aqueous solution many substances whose solubility in pure water or salt solutions is extremely low. The remarkable capacity of certain globulin fractions— notably those from Fractions III-O and IV-1, as separated by the low temperature-ethanol technique— to bind cholesterol, phos-phatides, and other types of lipid material, in stable, water-soluble combination has already been described in the preceding section. Serum albumin, however, displays equally remarkable afiSnities for a somewhat different and extremely diverse group of substances, including many types of acid and basic dyes, the ions of many organic acids containing hydrocarbon residues, certain quinone derivatives, and other substances. 

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