Pharmaceutical compositions comprising monoterpenes

• US 9,700,524 B2
• Filed: 02/10/2016
• Issued: 07/11/2017
• 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:
  US15/040,002
• Publication Number:
  US 20160158162A1
• Time in Patent Office: 517 Days
• Field of Search: 568826, 568875, 514 133, 514 193
• 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 method for treating a tumor of the nervous system, comprising the step of delivering to a subject in need thereof a therapeutically effective amount of (S)-perillyl alcohol, the (S)-perillyl alcohol having a purity of greater than about 98.5% (w/w).

2. The method of claim 1, wherein the tumor is a glioblastoma.

3. The method of claim 1, further comprising the step of treating the subject in need thereof with radiation.

4. The method of claim 1, further comprising the step of delivering to the subject in need thereof a chemotherapeutic agent.

5. The method of claim 4, wherein the chemotherapeutic agent is selected from the group consisting of a DNA alkyl ting agent, a topoisomerase inhibitor, an endoplasmic reticulum stress inducing agent, a platinum compound, an antimetabolite, an enzyme inhibitor, a receptor antagonist and a therapeutic antibody.

6. The method of claim 4, wherein the chemotherapeutic agent is dimethyl-celecoxib (DMC), irinotecan (CPT-11), temozolomide (TMZ) or rolipram.

7. The method of claim 1, wherein the (S)-perillyl alcohol is delivered by inhalation, intranasally, orally, intravenously, subcutaneously or intramuscularly.

8. The method of claim 1, wherein the (S)-perillyl alcohol is admixed or coformulated with a therapeutic agent.

9. The method of claim 8, wherein the therapeutic agent is a chemotherapeutic agent.

10. A method for inhibiting growth of a cell, comprising the step of contacting the cell with an effective amount of (S)-perillyl alcohol, wherein the (S)-perillyl alcohol has a purity of greater than about 98.5% (w/w), wherein the cell is a glioma cell, a meningioma cell, a pituitary adenoma cell, a lung cancer cell, a prostate cancer cell, a breast cancer cell a hematopoietic cancer cell cancer stem cell or an ovarian cancer cell.

11. The method of claim 10, her in the cell is temozolomide resistant cell.

12. The method of claim 10, wherein the contacting is in vitro.