Reduction in cpc taste aversion by reducing cpc activation of trpa1, tprv1, or both

Patent metadata

Field	Value
Publication number	US-2016296445-A1
Application number	US-201615094092-A
Country	US
Kind code	A1
Filing date	Apr 8, 2016
Priority date	Apr 9, 2015
Publication date	Oct 13, 2016
Grant date	—

Abstract

A method for screening compounds and compositions that reduce cetyl pyridinium chloride activation of TRPA1 receptor or TRPV1 receptor.

First claim

What is claimed is:

1 . A method of reducing cetyl pyridinium chloride (CPC) TRPA1 receptor or TRPV1 receptor activation comprising:
a. providing a cell that expresses at least one of TRPA1 receptor or TRPV1 receptor; b. adding CPC to the cell: c. adding at least one of a CPC TRPA1 receptor antagonist or CPC TRPV1 receptor antagonist; d. measuring receptor activation of at least one of the TRPA1 receptor or TRPV1 receptor.

2 . The method of claim 1 , wherein the receptor activation is measured by quantifying intracellular Ca 2+ levels as measured by FLIPR calcium flux.

3 . The method of claim 2 , wherein a fluorescent dye is used to quantify intracellular Ca 2+ levels.

4 . The method of claim 2 , wherein CPC TRPA1 receptor antagonist at a concentration of 1 mM reduces TRPA1 receptor activation by 375 μM cetyl pyridinium chloride (CPC), by at least 20% below the activation of TRPA1 receptor by 375 μM cetyl pyridinium chloride.

5 . The method of claim 4 , wherein the CPC TRPA1 receptor antagonist at a concentration of greater than 1 mM does not reduce TRPA1 receptor activation by 50 μM allyl isothiocyanate by at least 20% below the activation of TRPA1 receptor by 50 μM allyl isothiocyanate.

6 . The method of claim 1 , wherein the CPC TRPA1 receptor antagonist comprises at least one of eugenyl isovalerate; b-cyclodextrin; maltyl isobutyrate; tannic acid; manganese gluconate; p-mentha-8-thiol-3-one; myrtenol; manganese citrate.

7 . The method of claim 2 , wherein CPC TRPV1 receptor antagonist at a concentration of 1 mM reduces TRPV1 receptor activation by 375 μM cetyl pyridinium chloride (CPC) by at least 1000 counts or 20% below the activation of TRPV1 receptor by 375 μM cetyl pyridinium chloride (CPC).

8 . The method of claim 7 , wherein the CPC TRPV1 receptor antagonist at a concentration of greater than 1 mM does not reduce TRPV1 receptor activation by 350 nM capsaicin by at least 20% below the activation of TRPV1 receptor by 350 nM capsaicin.

9 . The method of claim 1 , wherein the CPC TRPV1 receptor antagonist comprises at least one of zinc acetate; 2-octenoic acid; 2-aminobenzoic acid naphthalene-2-yl ester; α-dimethylphenethyl butyrate; α-ionol; 4-(4-hydroxy-phenyl)-butan-2-one; butyl isobutyrate; uteramine; β-ionol; 2-methoxycinnamaldehyde; 4-(4-methoxyphenyl)-2-butanone; β-ionone; N,N-dimethylanthranilic acid methyl ester; methyl 4-phenylbutyrate; or decyl acetate.

10 . A method for screening compounds that reduce CPC TRPA1 or TRPV1 receptor activation by cetyl pyridinium chloride (CPC) comprising:
a. providing a cell that expresses at least one of a TRPA1 receptor or TRPV1 receptor; b. adding CPC to the cell; c. adding a test composition to the cell; d. measuring receptor activation of at least one of the TRPA1 receptor or TRPV1 receptor; e. determining if TRPA1 receptor or TRPV1 receptor activation was reduced as compared to adding CPC to a cell without adding a test composition.

11 . The method of claim 10 , wherein the receptor activation is measured by quantifying intracellular Ca 2+ levels as measured by FLIPR calcium flux.

12 . The method of claim 11 , wherein a fluorescent dye is used to quantify intracellular Ca 2+ levels.

13 . A personal care composition comprising:
a. CPC; and b. at least one of a CPC TRPA1 receptor antagonist or CPC TRPV1 receptor antagonist.

14 . The personal care composition of claim 13 , wherein the CPC TRPA1 receptor antagonist at a concentration of 1 mM reduces TRPA1 receptor activation by 375 μM cetyl pyridinium chloride (CPC), by at least 20% below the activation of TRPA1 receptor by 375 μM cetyl pyridinium chloride.

15 . The personal care composition of claim 14 , wherein the CPC TRPA1 receptor antagonist at a concentration of greater than 1 mM does not reduce TRPA1 receptor activation by 50 allyl isothiocyanate by at least 20% below the activation of TRPA1 receptor by 50 allyl isothiocyanate.

16 . The personal care composition of claim 13 , wherein CPC TRPV1 receptor antagonist at a concentration of 1 mM reduces TRPV1 receptor activation by 375 μM cetyl pyridinium chloride (CPC) by at least 1000 counts or 20% below the activation of TRPV1 receptor by 375 μM cetyl pyridinium chloride (CPC).

17 . The personal care composition of claim 16 , wherein the CPC TRPV1 receptor antagonist at a concentration of greater than 1 mM does not reduce TRPV1 receptor activation by 350 nM capsaicin by at least 20% below the activation of TRPV1 receptor by 350 nM capsaicin.

18 . The personal care composition of claim 13 , wherein the CPC TRPA1 receptor antagonist comprises at least one of eugenyl isovalerate; b-cyclodextrin; maltyl isobutyrate; tannic acid; manganese gluconate; p-mentha-8-thiol-3-one; myrtenol; manganese citrate.

19 . The personal care composition of claim 13 , wherein the CPC TRPV1 receptor antagonist comprises at least one of zinc acetate; 2-octenoic acid; 2-aminobenzoic acid naphthalene-2-yl ester; α-dimethylphenethyl butyrate; α-ionol; 4-(4-hydroxy-phenyl)-butan-2-one; butyl isobutyrate; uteramine; β-ionol; 2-methoxycinnamaldehyde; 4-(4-methoxyphenyl)-2-butanone; β-ionone; N,N-dimethylanthranilic acid methyl ester; methyl 4-phenylbutyrate; or decyl acetate.

20 . The personal care composition of claim 13 , wherein the CPC TRPA1 receptor antagonist is maltyl isobutyrate and the CPC TRPV1 receptor antagonist is at least one of 4-(4-hydroxy-phenyl)-butan-2-one or methyl 4-phenyl butyrate.

Assignees

• Procter & Gamble

Inventors

• Haught John Christian
• Sreekrishna Koti Tatachar
• Lin Yakang
• Hightower Carrita Anne
• Lepont Pierig Jean-Marie

Classifications

• A61K31/4425

  Pyridinium derivatives, e.g. pralidoxime, pyridostigmine · CPC title

• A61K31/235

  having an aromatic ring attached to a carboxyl group · CPC title

• A61K8/4926 Primary

  having six membered rings · CPC title

• G01N33/6872

  Intracellular protein regulatory factors and their receptors, e.g. including ion channels · CPC title

• A61K31/045

  Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates · CPC title