Use of physiological cooling active ingredients, and agents containing such active ingredients

Patent metadata

Field	Value
Publication number	US-9718839-B2
Application number	US-201414533345-A
Country	US
Kind code	B2
Filing date	Nov 5, 2014
Priority date	Nov 20, 2009
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

The invention relates to a TRPM8 modulator for achieving a cooling effect on the skin or a mucous membrane.

First claim

The invention claimed is:

1. A method for in-vitro or in-vivo modulation of the cold-menthol receptor TRPM8, comprising bringing the receptor into contact with one or more compounds of formula (I):

wherein,
R 11 , R 12 and R 13 independently of one another are selected from the group consisting of: H; linear or branched C 1 -C 6 -alkyl groups, optionally carrying 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH 2 , OH, SH, halogen and linear or branched C 1 -C 6 -alkoxy groups; and linear or branched C 1 -C 6 -alkyloxy groups, optionally carrying 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH 2 , OH, SH, halogen and linear or branched C 1 -C 6 -alkoxy groups; or
R 11 and R 12 together with the carbon atoms to which they are bonded form a 4-, 5-, 6- or 7-membered, mono- or poly-unsaturated, carbo- or heterocyclic ring, which optionally carries 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of linear or branched C 1 -C 6 -alkyl groups and oxo groups (═O), and the ring-heteroatoms are identical or different and are selected from the group consisting of O, N and S;
X and Z independently of one another are selected from the group consisting of —O—, —S—, —NH—, —S(═O)—, and —S(═O) 2 — groups; and
Y is a linear or branched C 1 -C 8 -alkylene group, which optionally carries 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH 2 , OH, SH, halogen, and linear or branched C 1 -C 6 -alkoxy groups; or
X-Y-Z together with the carbon atoms to which they are bonded form a keto group; and salts of these compounds and optionally in pure stereoisomer form or as a mixture of stereoisomers;
provided that the following compounds are excluded from the compounds of formula (I)

2. The method according to claim 1 , wherein the receptor is brought into contact with at least one compound which, in an in vitro cellular activity test using cells which recombinantly express the human TRPM8 receptor, modulate the permeability of these cells for Ca 2+ ions.

3. The method according to claim 1 , wherein the modulating compound has an agonistic or antagonistic effect on the cellular Ca2+ ion permeability.

4. The method according to claim 1 , wherein the modulating compound is a TRPM8 receptor agonist.

5. A method for inducing a sensation of coldness in a human and/or an animal comprising contacting a human and/or animal with one or more compounds of formula (I) as defined in claim 1 .

6. A pharmaceutical composition comprising one or more compounds of formula (I) as defined in claim 1 .

7. A method for treating prostate carcinomas, bladder weakness, or pain comprising contacting a patient with one or more compounds of formula (I) as defined in claim 1 .

8. A method for inducing a sensation of coldness to packaging comprising adding one or more compounds of formula (I) as defined in claim 1 to the packaging.

9. A method for inducing a sensation of coldness to a textile comprising adding one or more compounds of formula (I) as defined in claim 1 to the textile.

10. A method for inducing a sensation of coldness in a human and/or an animal comprising contacting a human and/or animal with an agent comprising one or more compounds of formula (I) as defined in claim 1 , wherein the one or more compounds are selected from the group consisting of the compounds of Group A:
Compounds of Group A

LN
Structure

1

3

4

6

7

8

in a concentration of 0.00001 wt. %-10 wt. % in relation to the total weight of the agent in order to achieve a cooling effect on the skin or mucosa, which compared with an agent of the same composition, where only the compound or compounds selected from Group A is (are) exchanged for menthane carboxylic acid-N-ethylamide in the same concentration, the cooling effect is extended by at least 10 minutes.

11. An agent comprising one or more compounds of formula (I) as defined in claim 1 .

12. The agent according to claim 11 selected from the group consisting of:
a) pharmaceutical compositions;
b) foods;
c) mouth care compositions;
d) body care compositions; and
e) foams or gels.

13. An agent according to claim 11 selected from the group consisting of an aromatic blend and a pharmaceutical or cosmetic preparation for nutrition, oral hygiene or pleasure, comprising one, two, three or more of Compounds of Group B:
Compounds of Group B

Assignees

• Symrise Ag
• Basf Se

Inventors

• Subkowski Thomas
• Backes Michael
• Oertling Heiko
• Machinek Arnold
• Loges Hubert
• Simchen Ulrike
• Surburg Horst
• Bollschweiler Claus
• Wittenberg Jens
• Siegel Wolfgang

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P17/18

  Antioxidants, e.g. antiradicals (preparations for protection against sunlight A61Q17/00) · CPC title