Use of physiological cooling active ingredients, and agents containing such active ingredients
The invention relates to a TRPM8 modulator for achieving a cooling effect on the skin or a mucous membrane.
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
LN
Structure
1
3
4
6
7
8
14. An agent according to claim 13 comprising one or more selected from the group consisting of:
(1) one or more further substances with a physiological cooling effect, wherein the one or more further substance (i) cause a taste effect or (ii) do not cause a taste effect;
(2) one or more flavourings without physiological cooling effect; and
(3) one or more substances with a trigeminal or mouthwashing effect without physiological cooling effect.
15. A product comprising one or more compounds of formula (I) or formula (II) as defined in claim 1 , wherein the product is select from the group consisting of:
a) textile products;
b) packaging materials;
c) tobacco products;
d) remedies;
e) hygiene products, and
f) wet wipes.
16. A substance comprising one or more compounds of formula (I) as defined in claim 1 .
17. A method for achieving a cooling effect on the skin or mucosa comprising contacting the skin or mucosa with an agent comprising one or more compounds of formula (I) as defined in claim 1 sufficient to achieve a physiological cooling effect, wherein the one or more compounds are selected from the group consisting of compounds of Group A:
LN
Structure
1
3
4
6
7
8
wherein compared with an agent of the same composition, where only the compound or compounds selected from Group A is (are) exchanged for methane carboxylic acid-N-ethylamide in the same concentration, the physiological cooling effect is extended by at least 10 minutes.
18. An agent according to claim 11 for alleviating the symptoms of coughs and colds, irritations, sore throat or hoarseness.