Pharmaceutical compositions comprising monoterpenes
The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w/w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w/w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.
1. A process for purifying (S)-perillyl alcohol comprising the steps of:
(a) derivatizing a mixture comprising (S)-perillyl alcohol to form a perillyl alcohol derivative;
(b) crystallizing the perillyl alcohol derivative using a solvent selected from the group consisting of a ketone solvent, nitrile solvent, halogenated solvent, ester solvent, ether solvent and hydrocarbon solvent or a mixture thereof;
(c) separating the perillyl alcohol derivative crystals from the mixture;
(d) releasing the (S)-perillyl alcohol from the separated perillyl alcohol derivative from step (c); and,
(e) isolating the (S)-perillyl alcohol from step (d),
wherein the isolated (S)-perillyl alcohol has a purity of greater than about 98.5% (w/w).
2. The process of claim 1 , wherein the perillyl alcohol derivative is a perillyl alcohol ester.
3. The process of claim 2 , wherein the ester is a benzoate ester.
4. The process of claim 3 , wherein the benzoate ester is 3,5-dinitrobenzoate ester.
5. The process of claim 1 , wherein the isolated (S)-perillyl alcohol has a purity of greater than about 99.0% (w/w).
6. The process of claim 5 , wherein the isolated (S)-perillyl alcohol has a purity of greater than about 99.5% (w/w).
7. The process of claim 1 , wherein the mixture further comprises natural-product-derived or other impurities.
8. The process of claim 1 wherein the ketone solvent is selected from the group consisting of acetone, methyl ethyl ketone, methyl isobutyl ketone, n-butanone and t-butyl ketone.
9. The process of claim 1 wherein the nitrile solvent is selected from the group consisting of acetonitrile and propionitrile.
10. The process of claim 1 wherein the halogenated solvent is selected from the group consisting of dichloromethane, 1,2 dichloroethane and chloroform.
11. The process of claim 1 wherein the ester solvent is selected from the group consisting of ethyl acetate, n-propyl acetate, isopropyl acetate and t-butyl acetate.
12. The process of claim 1 wherein the hydrocarbon solvent is selected from the group consisting of hexanes, cyclohexane, toluene and xylene.
13. The process of claim 1 wherein the ether solvent is selected from the group consisting of diethyl ether, diisopropyl ether, methyl-t-butyl ether, tetrahydrofuran and 1,4 dioxane.
14. The process of claim 13 wherein the ether solvent is diisopropyl ether.
15. The process of claim 13 wherein the ether solvent is methyl-t-butyl ether.