Methods and compositions for preventing and relieving muscle cramps and for recovery from neuromuscular irritability and fatigue following exercise

Abstract

The methods and compositions of the present invention are directed to the treatment or amelioration of muscle cramps using a composition that includes one or more TRPV1 channel activators, and/or one or more TRPA1 channel activators, and/or one or more ASIC channel activators.

1 . A method for treating or preventing muscle cramps or musculoskeletal irritability, or for improving muscle recovery in a subject in need thereof, said method comprising administering to said subject a composition formulated for oral ingestion comprising an effective amount of one or more TRPV1 channel activators, TRPA1 channel activators, ASIC channel activators, or any combination thereof;
 wherein said composition is an oral formulation that is a liquid, beverage, gel, solid, semi-solid, chewing gum, or spray; and   wherein said composition is administered to said subject prior to exercise, during exercise or following exercise.   
     
     
         2 . The method of  claim 1 , wherein said channel activator is capable of activation of a channel in a gastroesophogeal neuron when administered to a subject. 
     
     
         3 . The method of  claim 1 , wherein said composition is administered to said subject 0-120 minutes prior to exercise, during exercise, or 0-360 minutes following exercise. 
     
     
         4 . The method of  claim 1 , wherein said TRPV1 channel activator is capsaicin or is selected from the group consisting of oleoylethanolamide, N-oleoyldopamine, 3-methyl-N-oleoyldopamine, oleamide, capsiate, a 1-monoacylglycerol having C18 and C20 unsaturated and C8-C12 saturated fatty acid, a 2-monoacylglycerol having C18 and C20 unsaturated fatty acids, miogadial, miogatrial, polygodial, a terpenoid with an alpha,beta-unsaturated 1,4-dialdehyde moiety, sanshool, evodiamine, acesulfame-K, cyclamate, CuSO 4 , ZnSO 4 , FeSO 4 , arvanil, anandamide, N-arachidonoyl-dopamine, flufenamic acid dopamide, a dopamine amide of fenamic acid, 4-hydroxynonenal, or 1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea, gingerol, and salts of magnesium. 
     
     
         5 . The method of  claim 1 , wherein said wherein said TRPA1 channel activator is allyl isothiocyanate, gingerol, or cinnamaldehyde, or is selected from the group consisting of acrolein, farnesyl thiosalicylic acid, Δ 9 -tetrahydrocannabinol, eugenol, a shogaol, a sanshool, nicotine, nicotine derivatives or analogs, methyl salicylate, allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, sanshools, farnesyl thiosalicylic acid, and farnesyl thioacetic acid. 
     
     
         6 . The method of  claim 1 , wherein said ASIC channel activator is an acidulant selected from acetic acid, phosphoric acid, citric acid, malic acid, succinic acid, tartaric acid, fumaric acid, and ascorbic acid. 
     
     
         7 . The method of  claim 1 , wherein said composition comprises an effective amount of two or three different TRP channel activators independently selected from:
 (a) capsacin or other capsaicinoids;   (b) cinnamaldehyde or cinnamon oil; and   (c) gingerols.   
     
     
         8 . The method of  claim 1 , wherein each channel activator, independently, comprises between 0.001% to 1% weight percent of a composition that is a solid, semi-solid, gel, or chewing gum, or 0.001 to 1% (v/v) of a composition that is a liquid, beverage, or spray. 
     
     
         9 . The method of  claim 1 , wherein said subject is a human. 
     
     
         10 . A composition formulated for oral ingestion by a subject, said composition comprising an effective amount of one or more channel activators selected from TRPV1 channel activators, TRPA1 channel activators, and ASIC channel activators,
 wherein said composition is a liquid, beverage, gel, solid, semi-solid, chewing gum, or spray, and   wherein said composition has a pH greater than about 3.5.   
     
     
         11 . The composition of  claim 10 , wherein said channel activator is capable of activation of a channel in a gastroesophogeal neuron when administered to a subject. 
     
     
         12 . The composition of  claim 10 , wherein said TRPV1 channel activator is a capsaicinoid, oleoylethanolamide, N-oleoyldopamine, 3-methyl-N-oleoyldopamine, oleamide, capsiate, a 1-monoacylglycerol having C18 and C20 unsaturated and C8-C12 saturated fatty acid, a 2-monoacylglycerol having C18 and C20 unsaturated fatty acids, miogadial, miogatrial, polygodial, a terpenoid with an alpha,beta-unsaturated 1,4-dialdehyde moiety, sanshool, evodiamine, acesulfame-K, cyclamate, CuSO 4 , ZnSO 4 , FeSO 4 , arvanil, anandamide, N-arachidonoyl-dopamine, flufenamic acid dopamide, a dopamine amide of fenamic acid, 4-hydroxynonenal, or 1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea, or gingerol. 
     
     
         13 . The composition of  claim 12 , wherein said capsaicinoid is capsaicin. 
     
     
         14 . The composition of  claim 10 , wherein said TRPA1 channel activator is allyl isothiocyanate, gingerol, or cinnamaldehyde, acrolein, farnesyl thiosalicylic acid, Δ 9 -tetrahydrocannabinol, eugenol, a shogaol, a sanshool, nicotine, nicotine derivatives or analogs, methyl salicylate, allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, or farnesyl thioacetic acid. 
     
     
         15 . The composition of  claim 10 , wherein said ASIC activator is acetic acid, phosphoric acid, citric acid, malic acid, succinic acid, tartaric acid, fumaric acid, and ascorbic acid. 
     
     
         16 . The composition of  claim 10 , wherein each channel activator, independently, comprises between 0.001% to 1% (w/w) or 0.001 to 1% (v/v). 
     
     
         17 . The composition of  claim 10 , wherein said composition comprises, independently
 no more than two TRPV1 activators, and   no more than two TRPA1 activators.   
     
     
         18 . A composition for the activation of one or more TRP channel subtypes in a gastroesophogeal neuron, said composition comprising an effective amount of two or three different TRP channel activators independently selected from:
 (a) capsaicin or other capsaicinoids;   (b) cinnamaldehyde or cinnamon oil; and   (c) gingerols, and   wherein said composition is an oral formulation that is a liquid, beverage, gel, solid, semi-solid, chewing gum, or spray.   
     
     
         19 . The composition of  claim 18 , wherein said TRP channel activators are independently selected from:
 (a) capsicum;   (b) cinnamon volatile oil; and   (c) ginger oleoresin.   
     
     
         20 . The composition of  claim 19 , wherein
 component (a) is present in 0.001% to 1% (w/w) or 0.001% to 1% (v/v);   component (b) is present in 0.001% to 10% (w/w) or 0.001% to 10% (v/v); and/or   component (c) is present in 0.001% to 10% (w/w) or 0.001% to 10% (v/v)   
     
     
         21 . The composition of  claim 10 , wherein said composition is a liquid, beverage, or gel further comprising a viscosity modifier. 
     
     
         22 . The composition of  claim 10 , wherein said composition is a beverage or gel that is made by reconstituting a dry powder with an aqueous fluid. 
     
     
         23 . The composition of  claim 10 , wherein said composition is a packaged beverage or a packaged gel. 
     
     
         24 . The composition of  claim 23 , wherein said packaged beverage is provided in a unit that contains between 10-1000 mL of the beverage or said packaged gel is provided in a unit that contains between 5-100 g of the gel. 
     
     
         25 . The composition of  claim 24 , wherein said packaged beverage is provided in a unit that contains between 10-500 mL of the beverage or between 30-40 grams of the gel. 
     
     
         26 . A method of preparing the composition of  claim 10  for treating or ameliorating muscle cramps in a subject in need thereof, or for treating musculoskeletal irritability in a subject in need thereof, said method comprising the use of TRP or ASIC activator compounds that are substantially pure with an excipient to provide a composition that is a liquid, beverage, gel, solid, semi-solid, chewing gum, or spray.