CYP2J2 antagonists in the treatment of pain

Patent metadata

Field	Value
Publication number	US-11944613-B2
Application number	US-201916594790-A
Country	US
Kind code	B2
Filing date	Oct 7, 2019
Priority date	Aug 14, 2014
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

The present invention pertains to novel treatments of neuropathic pain; in particular chemotherapy induced peripheral neuropathic pain (CIPNP). The invention provides antagonists cytochrome P450 epoxygenases (CYP), and more specifically antagonists of CYP2J2, as therapeutics for use in the treatment of neuropathic pain such as CIPNP. CYP2J2 antagonists were identified to alleviate CIPNP in-vivo, and therefore are provided additionally in combination with chemotherapeutics for the treatment of diseases such as cancer or other proliferative disorders. The CYP2J2 antagonists reduce chemotherapeutic induced pain and therefore allow for a higher dosing of the chemotherapeutic during cancer treatment. In addition the invention relates to the use of CYP2J2 agonists, or metabolites of CYP2J2, for sensitizing TRPV1. In this context the invention proposes to use combinations of CYP2J2 agonist or metabolites and transient receptor potential vanilloid 1 (TRPV1) agonists to treat disorders that respond to TRPV1 agonists, such as neuropathic pain.

First claim

The invention claimed is:

1. A method for treating chemotherapy induced peripheral neuropathic pain (CIPNP) in a subject in need of the treatment, the method comprising:
administering to the subject a therapeutically effective amount of a cytochrome P450 epoxygenase 2J2 (CYP2J2) antagonist to treat the CIPNP, the CYP2J2 antagonist selected from the group consisting of estradiol, clobetasol propionate, doxazosin mesylate, fenofibrate, levonorgestrel, aripiprazole, halcinonide, telmisartan, levothyroxine-Na, alosetron-HCl, fluocinonide, and liothyronine-Na.

2. The method according to claim 1 , wherein the CYP2J2-antagonist is telmisartan.

3. The method according to claim 1 , comprising administering the therapeutically effective amount of the cytochrome P450 epoxygenase 2J2 (CYP2J2) antagonist to the subject prior to, during, or after a chemotherapy treatment on the subject.

4. The method according to claim 3 , wherein the chemotherapy comprises the administration of a chemotherapeutic agent to the subject, and wherein the chemotherapeutic agent is selected from the group consisting of a Cytarabine and Five Fluorouracil, a platin agent and a taxane.

5. The method according to claim 3 , wherein the chemotherapy comprises the administration of a chemotherapeutic agent to the subject, and wherein the chemotherapeutic agent is paclitaxel, docetaxel or cabazitaxel.

6. The method according to claim 3 , comprising administering the therapeutically effective amount of the cytochrome P450 epoxygenase 2J2 (CYP2J2) antagonist to the subject before the chemotherapy treatment on the subject.

Assignees

• Fraunhofer Ges Forschung

Inventors

• Sisignano Marco
• Brenneis Christian
• Scholich Klaus
• Geisslinger Gerd
• Zinn Sebastian
• Parnham Michael John

Classifications

• A61K31/445 Primary

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K31/138

  Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) · CPC title

• A61K31/198

  Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) · CPC title

• A61K31/216

  of acids having aromatic rings, e.g. benactizyne, clofibrate · CPC title

• A61K31/4184

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title