Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1986-05-28
1990-05-29
Wiseman, Thomas G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 54, 435 84, 435197, 536 53, A61K 31715, C12P 1926, C12N 916, C07H 1310
Patent
active
049296043
ABSTRACT:
An acyloxyacyl hydrolase from the human promyelocyte cell line HL-60 has been found to specifically hydrolyze fatty acids form their ester linkages to hydroxy groups of 3-hydroxyfatty acids, the latter being bound in turn to LPS glycosaminyl residues. The hydrolyzed fatty acids may include dodecanoic acid, tetradecanoic acid and hexadecanoic acid. This enzyme showed a molecular weight between about 50,000 daltons and about 70,000 daltons.
Altered bacterial LPS substantially without fatty acids bound in ester linkage to hydroxy groups of 3-hydroxyfatty acids covalently linked to a glucosaminyl moiety of LPS lipid A are produced. Since the structure of the lipid A moiety is highly conserved, acyloxyacyl hydrolase may act on LPS of many different pathogenic bacteria (for example Salmonella, Escherichia, Hemophilus, and Neisseria).
Such altered bacterial LPS, having toxicity reduced more than immunostimulatory activity, may be therapeutically useful: (1) as vaccines to prevent Gram-negative bacterial diseases by inducing antibodies to LPS 0-polysaccharide or R-core antigens, (2) as antidotes to treat or prevent gram-negative bacterial sepsis ("septic shock"), or (3) as adjuvants to enhance formation of antibodies to other antigens. The acyloxyacyl hydrolase itself may be therapeutically useful to detoxify endogenous LPS in patients with gram-negative bacterial diseases or to remove toxic LPS from therapeutic injectants.
REFERENCES:
patent: 4057685 (1977-11-01), McIntire
patent: 4148877 (1979-04-01), Choay et al.
patent: 4185090 (1980-01-01), McIntire
patent: 4242270 (1980-12-01), Ayme et al.
patent: 4435386 (1984-03-01), Ribi et al.
patent: 4436727 (1984-03-01), Ribi
patent: 4436728 (1984-03-01), Ribi et al.
patent: 4505899 (1985-03-01), Ribi et al.
patent: 4505900 (1985-03-01), Ribi et al.
patent: 4677194 (1987-06-01), Hao
Ribi, E. et al., (1982) Cancer Immunol. Immunother. 12, 91-96.
Takayama, K. et al., (1981), Cancer Res. 41, 2654-2657.
Qureshi, N. et al., (1982), J. Biol. Chem. 257 (19), 11808-11815.
Kotani et al., (1985), Infect. Immun., 49:225-237.
Tacata et al. (1985), Infect. Immun., 48:219-227.
Homma et al. (1985), J. Biochem., 98:395.
Galanos et al. (1984), Eur. J. Biochem., 140:221-227.
Hall and Munford (1983), Proc. Natl. Acad. Sci. U.S.A., 80:6671-6675.
Rosner et al. (1979), J. Biol. Chem., 254:5926-5933.
Gimber and Rafter (1969), Arch. Biochem. Biophys., 135:14-20.
Munford and Hall (1985), Infect. Immun., 48:464-473.
Vernet (1984), Rev. Inf. Dis., 6:452-454.
Freudenberg et al. (1984), Rev. Inf. Dis., 6:483-487.
Kotani et al. (1984), Infect. Immun., 485:293-296.
Sutherland (1977), "Surface Carbohydrates of the Prokaryotic Cell", pp. 236-239.
Dialog and Lexpat Search of the Scientific and Patent Literature.
Hall Catherine L.
Munford Robert S.
Board of Regents , The University of Texas System
Patterson Jr. Charles L.
Wiseman Thomas G.
LandOfFree
Lipopolysaccharides of reduced toxicity and the production there does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Lipopolysaccharides of reduced toxicity and the production there, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Lipopolysaccharides of reduced toxicity and the production there will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-520930