Pharmaceutical compositions comprising monoterpenes

• US 9,480,659 B2
• Filed: 08/04/2015
• Issued: 11/01/2016
• Est. Priority Date: 03/03/2010
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: Neonc Technologies Inc.
• Inventors: Chen, Thomas, Levin, Daniel, Puppali, Satish
• Primary Examiner(s): Bakshi, Pancham
• Application Number:
  US14/817,286
• Publication Number:
  US 20150368173A1
• Time in Patent Office: 455 Days
• Field of Search: 568/437, 568/854, 568/875
• US Class Current: 1/1
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 201/12 by reactions not involving the formation of nitro groups
• CPC Class Codes: C07C 201/16 Separation; Purification; Stabilisation; Use of additives
• CPC Class Codes: C07C 205/57 having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
• CPC Class Codes: C07C 2601/16 the ring being unsaturated
• CPC Class Codes: C07C 29/78 by condensation or crystallisation
• CPC Class Codes: C07C 29/86 by liquid-liquid treatment
• CPC Class Codes: C07C 29/88 by treatment giving rise to a chemical modification of at least one compound chemisorption C07C29/76
• CPC Class Codes: C07C 29/92 by a consecutive conversion and reconstruction
• CPC Class Codes: C07C 33/14 containing six-membered rings
• CPC Class Codes: C07C 67/14 from carboxylic acid halides
• CPC Class Codes: C07C 69/76 Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 69/92 with etherified hydroxyl groups

Abstract

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.

Claims

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.