Compositions and methods of reducing side effects and toxicity of methotrexate when given as orotate derivatives
AssigneeSavvipharm Inc
InventorRashida A. Karmali
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Abstract
This invention is in the field of chemical restructuring of antimetabolite agents known to have poor oral bioavailability and to cause tissue toxicity as a side effect, by producing their orotate derivatives. More particularly, it concerns orotate derivatives of the methotrexate and trimetrexate, that are found to improve the oral bioavailability and clearance compared with their respective forms- methotrexate and trimetrexate, currently in use. The present invention provides methotrexate orotate having the formula:
Claims5
A method of making an orotate derivative of an antimetabolite agent, said method comprising:
- mixing an alkali solvent selected from the group consisting of potassium hydroxide, sodium hydroxide and aluminuim hydroxide, with the orotic acid;
- mixing and drying the resulting precipitate of alkali orotate, and
- reacting the alkali orotate formed with the antimetabolite agent, to obtain the orotate derivative of the antimetabolite agent.
The method according to claim I wherein the antimetabolite is selected from the group consisting of methotrexate and trimetrexate.
A method of improving the oral bioavailability of an antimetabolite by using an orotate derivative of the antimetabolite, wherein the wherein the antimetabolite is selected from the group consisting of methotrexate and trimetrexate.
A method of improving the clearance of an antimetabolite by usiung an orotate derivative of the antimetabolite, wherein the antimetabolite is selected from the group consisting of methotrexate and trimetrexate.
A compound having the formula:
Dependencies are inferred from the claim text.