Preparation and properties of an alpha-1-protease inhibitor concentrate with high specific activity.
OBJECTIVE
Because the current demand for alpha-1-protease inhibitor (A1PI) exceeds the available supply, we aimed to develop a process for purification of A1PI from plasma which would achieve the highest possible degree of purity, specific activity and yield.


METHODS
A1PI was purified from Cohn fraction IV-1,4 using ethanol precipitation and Q-Sepharose chromatography. Ceramic hydroxyapatite chromatography was used as a final purification step. Two independent virus-inactivation procedures (chemical and vapour heating) were applied.


RESULTS
The resulting A1PI had an unprecedented high specific activity. In addition, the process led to the discovery of a new isoform of A1PI in isoelectric focusing gels.


CONCLUSIONS
The high specific activity of the A1PI preparation achieved with this process should allow a reduction of the A1PI total protein load necessary to achieve clinically relevant effects.
Mattes
E
E
Baxter Hyland Immuno, Vienna, Austria.
Matthiessen
H P
HP
Turecek
P L
PL
Schwarz
H P
HP
D001798:Blood Proteins / Q000737:chemistry; D011232:Chemical Precipitation; D002847:Chromatography, Agarose; D006801:Humans; D007525:Isoelectric Focusing; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D020033:Protein Isoforms; D015842:Serine Proteinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000592:standards; D013242:Sterilization; D013810:Therapeutic Equivalency; D014361:Trypsin Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000592:standards; D000515:alpha 1-Antitrypsin / Q000302:isolation & purification* / Q000494:pharmacology / Q000592:standards*
D001798:Blood Proteins; C032309:Cohn fraction IV; D020033:Protein Isoforms; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase