PREPARATION AND PROPERTIES OF A THERAPEUTIC INTER-ALPHA-TRYPSIN INHIBITOR CONCENTRATE FROM HUMAN PLASMA

Citation
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
Citations number
29
Categorie Soggetti
Hematology
Journal title
ISSN journal
00429007
Volume
67
Issue
4
Year of publication
1994
Pages
329 - 336
Database
ISI
SICI code
0042-9007(1994)67:4<329:PAPOAT>2.0.ZU;2-9
Abstract
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.