Excitatory amino acid inhibitors for treating sensitive skins

Abstract

Sensitive human skin/scalp/mucous membrane conditions, for example skin irritation and/or dry patches and/or erythemas and/or dysaesthesic sensations and/or sensations of heating and/or pruritus, are therapeutically treated by topically applying thereto an effective condition-alleviating amount of at least one inhibitor of at least one excitatory amino acid.

1 . A method for treating dysaesthesic sensations of sensitive skin or scalp in an individual, where said dysaesthesic sensations result from at least one factor or challenge selected from the group consisting of: rubbing, shaving, soap, surfactants, hard water having a high calcium concentration, temperature variations, wool, foods, the wind, the environment and emotions, said method comprising:
 decreasing the release, synthesis or binding of an aspartate or glutamate excitatory amino acid by nerve fibers in the epidermis or dermis of said individual having sensitive skin or scalp by topically applying to said sensitive skin or scalp of said individual, a cosmetic or dermatological composition comprising at least one inhibitor of said aspartate or glutamate excitatory amino acid in an amount effective to treat dysaesthesic sensations of said sensitive skin or scalp, formulated into a physiologically acceptable medium therefor;   wherein said at least one inhibitor of aspartate or glutamate excitatory amino acid has at least one of the following properties:   (a) has pharmacological activity, as measured by electrophoresis, as being a receptor antagonist to one of the receptors of at least one excitatory amino acid selected from the group consisting of AMPA (L-α-amino-3-hydroxy-5-methyl-4-isoxazole propionate), NMDA (N-methyl-D-aspartate) and kainate;   (b) lowers the extravasation of plasma, as measured by the Evans Blue method, observed after antidromic stimulation of the saphene nerve or after stimulation with capsaicin; and   (c) lowers the cellular cytotoxicity induced on neuronal cell lines after incubation with high concentrations of glutamate; and   wherein said sensitive skin is determined to be sensitive by applying 0.05 ml of a cream containing 0.075% capsaicin to about 4 cm 2  of skin and said application of capsaicin results in the appearance of subjective signs caused by this application, such as stinging, burning and itching, where these signs appear between 3 and 20 minutes after topical application and are followed by the appearance of an erythema which begins at the periphery of the zone of application.   
   
   
       2 . The method according to  claim 1 , wherein said sensitive skin is irritable or reactive skin. 
   
   
       3 . The method according to  claim 1 , wherein said sensitive skin is intolerant skin. 
   
   
       4 . The method according to  claim 1 , wherein said dysaesthesic sensations are selected from the group consisting of stinging, tingling, itching, pruritus, heating, discomfort, tautness and erythema. 
   
   
       5 . The method according to  claim 1 , wherein said physiologically acceptable medium is selected from the group consisting of an aqueous solution, an aqueous-alcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, an aqueous gel, an anhydrous gel, a serum, and a vesicle dispersion. 
   
   
       6 . The method according to  claim 1 , wherein said at least one inhibitor is applied in an amount ranging from 0.00001 to 5% by weight relative to the total weight of the composition. 
   
   
       7 . The method according to  claim 1 , wherein said at least one inhibitor is applied in an amount ranging from 0.0001 to 1% by weight relative to the total weight of the composition. 
   
   
       8 . The method according to  claim 1 , wherein said composition further comprises at least one agent selected from the group consisting of an antibacterial agent, antiparasitic agent, antifungal agent, anti-inflammatory agent, anti-pruriginous agent, anaesthetic, antiviral agent, keratolytic agent, anti-free-radical agent, anti-seborrhoeic agent, antidandruff agent, antiacne agent, an agent which modifies skin differentiation, an agent which modifies skin proliferation, and an agent which modifies skin pigmentation. 
   
   
       9 . A method for treating dysaesthesic sensations of sensitive skin or scalp in an individual, where said dysaesthesic sensations result from at least one factor or challenge selected from the group consisting of: rubbing, shaving, soap, surfactants, hard water having a high calcium concentration, temperature variations, wool, foods, the wind, the environment and emotions, said method comprising:
 decreasing the release, synthesis or binding of an aspartate or glutamate excitatory amino acid by nerve fibers in the epidermis or dermis of said individual having sensitive skin or scalp by topically applying to said sensitive skin or scalp of said individual, a cosmetic or dermatological composition comprising at least one active agent having an irritant side effect, in an amount effective to cause irritation of said sensitive skin or scalp, and at least one inhibitor of said aspartate or glutamate excitatory amino acid, in an amount effective to attenuate or eliminate said irritation, formulated into a physiologically acceptable medium therefor;   wherein said at least one inhibitor of aspartate or glutamate excitatory amino acid has at least one of the following properties:   (a) has pharmacological activity, as measured by electrophoresis, as being a receptor antagonist to one of the receptors of at least one excitatory amino acid selected from the group consisting of AMPA (L-α-amino-3-hydroxy-5-methyl-4-isoxazole propionate), NMDA (N-methyl-D-aspartate) and kainate;   (b) lowers the extravasation of plasma, as measured by the Evans Blue method, observed after antidromic stimulation of the saphene nerve or after stimulation with capsaicin; and   (c) lowers the cellular cytotoxicity induced on neuronal cell lines after incubation with high concentrations of glutamate; and   wherein said sensitive skin is determined to be sensitive by applying 0.05 ml of a cream containing 0.075% capsaicin to about 4 cm 2  of skin and said application of capsaicin results in the appearance of subjective signs caused by this application, such as stinging, burning and itching, where these signs appear between 3 and 20 minutes after topical application and are followed by the appearance of an erythema which begins at the periphery of the zone of application.   
   
   
       10 . The method of  claim 9 , wherein said at least one active agent having an irritant side effect in said a cosmetic or dermatological composition is selected from the group consisting of α-hydroxy acids, β-hydroxy acids, α-keto acids, β-keto acids, retinoids, anthralins, anthranoids, peroxides, lithium salts, antimetabolites and vitamin D. 
   
   
       11 . The method according to  claim 9 , wherein said sensitive skin is irritable or reactive skin. 
   
   
       12 . The method according to  claim 9 , wherein said sensitive skin is intolerant skin. 
   
   
       13 . The method according to  claim 9 , wherein said irritation comprises dysaesthesic sensations selected from the group consisting of stinging, tingling, itching, pruritus, heating, discomfort, tautness and erythema. 
   
   
       14 . The method according to  claim 9 , wherein said physiologically acceptable medium is selected from the group consisting of an aqueous solution, an aqueous-alcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, an aqueous gel, an anhydrous gel, a serum, and a vesicle dispersion. 
   
   
       15 . The method according to  claim 9 , wherein said at least one inhibitor is applied in an amount ranging from 0.00001 to 5% by weight relative to the total weight of the composition. 
   
   
       16 . The method according to  claim 9 , wherein said at least one inhibitor is applied in an amount ranging from 0.0001 to 1% by weight relative to the total weight of the composition. 
   
   
       17 . A method for treating sensitive skin, said method comprising decreasing the release, synthesis or binding of an aspartate or glutamate excitatory amino acid by nerve fibers in the epidermis or dermis of an individual having sensitive skin or scalp and in need of treatment thereof by topically applying to the sensitive skin or scalp of said individual, a cosmetic or dermatological composition comprising at least one inhibitor of said aspartate or glutamate excitatory amino acid in an amount effective to treat dysaesthesic sensations of said sensitive skin or scalp, formulated into a physiologically acceptable medium therefor. 
   
   
       18 . The method according to  claim 17 , wherein said at least one inhibitor is selected from the group consisting of ketamine, memantine, (±)-2-amino-3-phosphonopropionic acid, ±-2-amino-4-phosphonobutyric acid, ±-2-amino-5-phosphonopentanoic acid, D-8-glutamylaminomethanesulfonic acid, 1,2,3,6,7,8-hexahydro-3-(hydroxyimino)-N,N,7-trimethyl-2-oxobenzo[2,1-b:3,4-c′]dipyrrole-5-sulfonamide hydrochloride (NS 257, HCl), cyclothiazide, aniracetam, riluzole, and mixtures thereof. 
   
   
       19 . The method according to  claim 17 , wherein said dysaesthesic sensations are selected from the group consisting of stinging, tingling, itching, pruritus, heating, discomfort, tautness and erythema. 
   
   
       20 . A method for treating sensitive skin, said method comprising decreasing the release, synthesis or binding of an aspartate or glutamate excitatory amino acid by nerve fibers in the epidermis or dermis of an individual having sensitive skin or scalp and in need of treatment thereof by topically applying to the sensitive skin or scalp of said individual, a cosmetic or dermatological composition comprising at least one active agent having an irritant side effect, in an amount effective to cause irritation of said sensitive skin or scalp, and at least one inhibitor of said aspartate or glutamate excitatory amino acid, in an amount effective to attenuate or eliminate said irritation, formulated into a physiologically acceptable medium therefor. 
   
   
       21 . The method according to  claim 20 , wherein said at least one inhibitor is selected from the group consisting of ketamine, memantine, (±)-2-amino-3-phosphonopropionic acid, ±-2-amino-4-phosphonobutyric acid, ±-2-amino-5-phosphonopentanoic acid, D-8-glutamylaminomethanesulfonic acid, 1,2,3,6,7,8-hexahydro-3-(hydroxyimino)-N,N,7-trimethyl-2-oxobenzo[2,1-b:3,4-c′]dipyrrole-5-sulfonamide hydrochloride (NS 257, HCl), cyclothiazide, aniracetam, riluzole, and mixtures thereof. 
   
   
       22 . The method according to  claim 20 , wherein said dysaesthesic sensations are selected from the group consisting of stinging, tingling, itching, pruritus, heating, discomfort, tautness and erythema. 
   
   
       23 . The method of  claim 20 , wherein said at least one active agent having an irritant side effect in said a cosmetic or dermatological composition is selected from the group consisting of α-hydroxy acids, α-hydroxy acids, α-keto acids, β-keto acids, retinoids, anthralins, anthranoids, peroxides, lithium salts, antimetabolites and vitamin D.