Linked Life Data

8926578

Source:http://linkedlifedata.com/resource/pubmed/id/8926578

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-10-25
pubmed:abstractText
The stability of the immunologic adjuvant QS-21 (Cambridge Biotech Corp.) was optimized for use in the MN rgp120 HIV-1 subunit vaccine. QS-21, a saponin purified by reversed phase HPLC from an extract of the bark of the Quillaja saponaria Molina tree, consisted initially of one species (QS-21A), but converted to two species, QS-21A and QS-21B, in aqueous solution. NMR studies indicated that the two species are structural isomers and that isomerization occurs by intramolecular trans-esterification of the fatty acid moiety between the 3- and 4-hydroxyl groups of the fucose ring (Jacobsen et al. Carbohydr. Res., in press). Both isomers were adjuvant active. Storage of QS-21 in aqueous solution resulted in the interconversion between these isomer forms, as well as the slow formation of degradation products due to ester hydrolysis. The critical micellar concentration of QS-21 in succinate buffer was measured by a fluorescent probe method to be 51 +/- 9 micrograms/mL. Studies were performed at different concentrations of QS-21 to assess the influence of micelle formation on stability. These experiments indicated that QS-21 is more stable in the micellar form, presumably because the most labile ester bond linking the fatty acid moiety to fucose is constrained or buried in the hydrophobic micellar environment. The pH of maximum stability was pH 5.5, the pH for minimum degradation of most esters. The final formulation, 500 micrograms/mL QS-21 in 20 mM sodium succinate, 150 mM NaCl, pH 5.5, provided a shelf-life of greater than 2 years.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3549
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Isomerization and formulation stability of the vaccine adjuvant QS-21.
pubmed:affiliation
Pharmaceutical R & D, Department Genentech, Inc., S. San Francisco, CA 94080-4990, USA.
pubmed:publicationType
Journal Article, Comparative Study