Prodrugs for oral administration containing taxol or substituted taxol covalently bound to a phospholipid
AssigneeVestar, Inc.
InventorsKarl Y. Hostetler, Nagarajan C. Sridhar
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Abstract
The oral delivery of many classes of drugs is facilitated by converting drugs having suitable functional groups to 1-O-alkyl-, 1-O-acyl-, 1-S-acyl, and 1-S-alkyl-sn-glycero-3-phosphate derivatives. The method confers the ability to be absorbed through the digestive tract to drugs that are not orally bioavailable in the non-derivatized state, and enhances the effectiveness of drugs that are poorly absorbed or rapidly eliminated. The method provides orally bioavailable lipid prodrugs of zaxol and taxol-related compounds. Potency of the lipid prodrugs is comparable to that of the corresponding nonderivatized drugs. In a preferred embodiment, taxol or substituted taxol is covalently bound to a phospholipid.
Claims6
An antineoplastic prodrug, comprising taxol, or a substituted taxol, covalently bound to a phospholipid compound, wherein said prodrug has the formula:
- ##STR4## wherein R.sup.1 and R.sup.2 are the same or different and are straight or branched, saturated or unsaturated C.sub.8 -C.sub.18 acyl or alkyl groups;
- or R.sup.2 is benzyl or OH;
- R.sup.3 is taxol, taxotene, baccatin III, or 10-deacetyl baccatin III;
- R.sup.4 is benzoyl, pivaloyl, acetate, peptides, or amino acids;
- and
- n is 0-10.
Dependencies are inferred from the claim text.