Pharmaceutical compositions comprising monoterpenes

• US 10,457,618 B2
• Filed: 07/26/2016
• Issued: 10/29/2019
• 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:
  US15/220,135
• Publication Number:
  US 20160332942A1
• Time in Patent Office: 1,190 Days
• Field of Search: 568854, 568875, 556437
• 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 consisting essentially of the steps of:

(a) derivatizing a mixture comprising (S)-perillyl alcohol to form a perillyl alcohol derivative, wherein the perillyl alcohol derivative is a 3,5-dinitrobenzoate ester derivative of perillyl alcohol;

(b) crystallizing the perillyl alcohol derivative;

(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).

2. The process of claim 1, wherein the isolated (S)-perillyl alcohol has a purity of greater than about 98.5% (w/w).

3. The process of claim 2, wherein the isolated (S)-perillyl alcohol has a purity of greater than about 99.0% (w/w).

4. The process of claim 1, wherein the mixture further comprises natural-product-derived or other impurities.

5. The process of claim 3, wherein the isolated (S)-perillyl alcohol has a purity of greater than about 99.5% (w/w).

6. A process for purifying perillyl alcohol comprising the steps of:

(a) derivatizing a mixture comprising perillyl alcohol to form a perillyl alcohol derivative, wherein the perillyl alcohol derivative is a 3,5-dinitrobenzoate ester derivative of perillyl alcohol;

(b) crystallizing the perillyl alcohol derivative;

(c) separating the perillyl alcohol derivative crystals from the mixture;

(d) releasing the perillyl alcohol from the separated perillyl alcohol derivative from step (c); and

,

(e) isolating the perillyl alcohol from step (d).

7. The process of claim 6, wherein the isolated perillyl alcohol has a purity of greater than about 98.5% (w/w).

8. The process of claim 7, wherein the isolated perillyl alcohol has a purity of greater than about 99.0% (w/w).

9. The process of claim 8, wherein the isolated perillyl alcohol has a purity of greater than about 99.5% (w/w).

10. The process of claim 6, wherein the mixture further comprises natural-product-derived or other impurities.

11. The process of claim 6, wherein the perillyl alcohol is (S)-perillyl alcohol.