Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,...
Patent
1992-03-23
1995-12-12
Kishore, Gollamudi
Drug, bio-affecting and body treating compositions
Conjugate or complex of monoclonal or polyclonal antibody,...
424 7827, 536 64, 436532, 436533, C08L 512, B61K 3174
Patent
active
054747651
ABSTRACT:
This invention discloses new targeted conjugates for the delivery of a compound, and particularly, a steroid, to vascular endothelial cells. The conjugates comprise two components, preferably linked by a selectively-hydrolyzable bond, such as an acid-labile bond or enzyme-sensitive bond. The first component, a polyanionic polymer, and preferably, a polysulphated polymer such as a heparin-derivative, specifically directs the conjugate to vascular endothelial cells. The second component is a selected agent, such as asteroid, which exerts a specific effect on the target cell following its release. In particular, the present invention provides novel conjugated angiogenesis inhibitors, for use in the treatment of pathogenic conditions including cancer, arthritis, and diabetic blindness. An inhibitor comprising a heparin derivative and the anti-angiogenic steroid, cortisol, is herein shown to be markedly acid-labile, to suppress DNA synthesis and cell migration in human umbilical vein endothelial cells, to retard or abolish (depending on the route of injection) the vascularization of sponges in vivo and to retard lung tumor growth in mice by 65%. No adverse effects of the conjugate were detected, and equivalent treatments with a mixture of heparin plus cortisol were significantly less effective in all cases.
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Kishore Gollamudi
Kulkosky Peter F.
UT SW Medical CTR at Dallas
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