C. Michalski et al., PREPARATION AND PROPERTIES OF A THERAPEUTIC INTER-ALPHA-TRYPSIN INHIBITOR CONCENTRATE FROM HUMAN PLASMA, Vox sanguinis, 67(4), 1994, pp. 329-336
Inter-alpha-trypsin inhibitor (ITI) is a serine protease inhibitor fou
nd in human plasma. Its antiprotease activity is due to bikunin which
is effective in various types of experimental shock and pancreatitis.
Therefore ITI, which releases bikunin by proteolytic cleavage, could b
e of therapeutic interest. A method for the large-scale isolation of I
TI from human plasma is described. ITI was purified from the prothromb
in complex concentrate (PCC) by diethylaminoethyl-Sepharose fast-flow
chromatography followed by a chromatographic step on immobilized hepar
in designed to remove C4, factor X and protein C. With this procedure,
which was performed under mild conditions, a homogeneous preparation
of native ITI was obtained, as demonstrated by electrophoretic and chr
omatographic analyses. ITI maintained its biological activity, as exhi
bited by its specific antitryptic activity of 420+/-65 IU/g. In order
to decrease or eliminate the risk of transmission of viral disease due
to lipid-enveloped viruses, the process incorporated a solvent-deterg
ent treatment. Animal studies on the final product revealed no adverse
side-effects in terms of toxicity, thrombogenicity or hypotension. Th
is preparation appears suitable for therapeutic evaluation in animal e
xperimental models.