Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Patent
1998-04-10
2000-04-25
Jones, Dwayne C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
514724, 514762, 514763, 514766, 568303, A61K 3100
Patent
active
060544902
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This application is a 371 of PCT/GB96/01118 filed May 4, 1996.
The present invention relates to substances and methods for inhibiting oxidative enzymes, and in particular for inhibiting enzymes responsible for the metabolism of bioactive agents to inactive or excretable derivatives thereof in vivo.
BACKGROUND OF THE INVENTION
Metabolism of bioactive agents (hereafter "drugs") to inactive or excretable derivatives is undesirable in many treatment regimes because it leads to a reduction in bioavailability. This may necessitate increasing dosage of the drug and this can lead to adverse side effects. The most significant enzymes responsible for such metabolism are the cytochrome P450 enzymes such as the CYP3A4 isozyme. Most agents known to inhibit CYP3A4 have significant adverse effects that make them unsuitable for co-administration with the drug.
The present invention aims to overcome these and other problems of the prior art.
SUMMARY OF THE INVENTION
The present invention relates to compositions comprising a pharmaceutically acceptable carrier, a compound which is unstable in the presence of an oxidative enzyme, and a sesquiterpene. In preferred embodiments, the present invention relates to compositions comprising: i) a pharmaceutically acceptable carrier; ii) a compound which is unstable in the presence of an oxidative enzyme; and iii) a sesquiterpene selected from the group consisting of nootkatol, nootkatone, nootkatol isomers, nootkatone isomers. In particular embodiments, the compound which is unstable in the presence of an oxidative enzyme is selected from the group consisting of taxol, cyclosporin, and dihydropyridine.
In other preferred embodiments, the present invention relates to compositions comprising: i) a pharmaceutically acceptable carrier; ii) a compound that is unstable in the presence of an oxidative enzyme, which is selected from the group consisting of taxol, cyclosporin, and dihydropyridine; and iii) a sesquiterpene. In particular embodiments, the sesquiterpene is selected from the group consisting of nootkatol, nootkatone, nootkatol isomers, nootkatone isomers, bicyclic sesquiterpenes, substituted sesquiterpenes, and oxidized sesquiterpenes.
In one embodiment of the inventive compositions, the sesquiterpene comprises approximately 0.1 to 10% of the invention composition. In certain embodiments, the inventive composition is in the form of a solid or a liquid, and is suitable for oral or intravenous administration to humans. In yet other embodiments, the invention composition comprises a compound which is unstable in the presence of cytochrome P450 oxidative enzyme. In particular embodiments, the cytochrome P450 enzyme is cytochrome P450 3A4.
Furthermore, the present invention relates to methods for inhibiting the action of at least one oxidative enzyme. In preferred embodiments, the present invention relates to methods for inhibiting the action of at least one oxidative enzyme, comprising the steps of: a) providing in any order: i) a composition comprising a pharmaceutically acceptable carrier, a compound which is unstable in the presence of an oxidative enzyme, and a sesquiterpene selected from the group consisting of nootkatol, nootkatone, nootkatol isomers and nootkatone isomers, and ii) one or more oxidative enzymes; and b) exposing the composition to one or more oxidative enzymes under conditions such that one or more oxidative enzymes is inhibited. In particular embodiments, the compound which is unstable in the presence of an oxidative enzyme is selected from the group consisting of taxol, cyclosporin, and dihydropyridine.
In other preferred embodiments, the present invention relates to methods for inhibiting the action of at least one oxidative enzyme, comprising the steps of: a) providing in any order: i) a composition comprising a pharmaceutically acceptable carrier, a sesquiterpene, and a compound that is unstable in the presence of an oxidative enzyme, which is selected from the group consisting of taxol and cyclosporin, and ii) one or more oxid
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Banister Nigel Eric
Cheetham Peter Samuel James
Gradley Michelle Lorraine
Sime John Thomas
Delacroix-Muirheid C.
Jones Dwayne C.
Zylepsis Limited
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