Topically administered strontium-containing complexes for treating pain, pruritis and inflammation
Therapeutically-active compositions that combine strontium with at least one additional molecules that increase the overall therapeutic potency of the combination beyond the potency of any of the separate constituents. Specifically, the combinations perform two important functions; (1) they increase the ability of topically-applied strontium to inhibit both acute sensory irritation (e.g., pruritus and pain), redness, swelling and inflammation (collectively defined for purposes of this description, “irritation”) and the chronic irritation that is characteristic of and contributes to the development and maintenance of painful or pruritic neuropathic conditions; and (2) they decrease the strontium activated pathways that are known to enhance the development and maintenance of pain, pruritis and neuropathic conditions.
1. A method of treating a condition selected from the group consisting of redness, swelling, and inflammation, comprising administering to a subject in need thereof a composition comprising a complex of:
a divalent strontium salt;
a cysteine-based anti-oxidant selected from the group consisting of N-acetyl cysteine, N-acetyl cysteinate, and esters thereof; and
a polyhydroxyphenol selected from the group consisting of gallic acid, caffeic acid, and mixtures thereof;
wherein the cysteine-based anti-oxidant and the polyhydroxyphenol are conjugated together by a thioester bond formed by a sulfhydryl group of the cysteine-based anti-oxidant and a carboxyl group of the polyhydroxyphenol.
2. The method of claim 1 , wherein the polyhydroxyphenol is gallic acid and esters thereof.
3. The method of claim 1 , wherein the divalent strontium salt is selected from the group consisting of strontium chloride, strontium chloride hexahydrate, strontium sulfate, strontium carbonate, strontium nitrate, strontium hydroxide, strontium hydrosulfide, strontium oxide, strontium acetate, strontium glutamate, strontium aspartate, strontium malonate, strontium maleate, strontium citrate, strontium threonate, strontium lactate, strontium pyruvate, strontium ascorbate, strontium alpha-ketoglutarate, and strontium succinate.
4. The method of claim 1 , wherein administering is topically administering.
5. The method of claim 1 , further comprising a polymer.
6. The method of claim 5 , wherein the polymer is selected from the group consisting of polyvinylpyrrolidone, cyclodextrins, carrageenan, alginic acid, xanthan gum, sulfated polysaccharides, pentosane polysulfate, chondroitin sulfate, dextran sulfate and heparin sulfate.
7. A method of treating inflammation, comprising administering to a subject in need thereof a composition comprising a complex of:
a divalent strontium salt;
a cysteine-based anti-oxidant selected from the group consisting of cysteine, N-acetyl cysteinate, N-acetyl cysteine, and esters thereof; and
a polyhydroxyphenol selected from the group consisting of gallic acid, caffeic acid, and mixtures thereof;
wherein the cysteine-based anti-oxidant and the polyhydroxyphenol are conjugated together by a thioester bond formed by a sulfhydryl group of the cysteine-based anti-oxidant and a carboxyl group of the polyhydroxyphenol.
8. The method of claim 7 , wherein the polyhydroxyphenol is gallic acid.
9. The method of claim 7 , wherein the divalent strontium salt is selected from the group consisting of strontium chloride, strontium chloride hexahydrate, strontium sulfate, strontium carbonate, strontium nitrate, strontium hydroxide, strontium hydrosulfide, strontium oxide, strontium acetate, strontium glutamate, strontium aspartate, strontium malonate, strontium maleate, strontium citrate, strontium threonate, strontium lactate, strontium pyruvate, strontium ascorbate, strontium alpha-ketoglutarate, and strontium succinate.
10. The method of claim 7 , wherein administering is topically administering.
11. The method of claim 7 , further comprising a polymer.
12. The method of claim 11 , wherein the polymer is selected from the group consisting of polyvinylpyrrolidone, cyclodextrins, carrageenan, alginic acid, xanthan gum, sulfated polysaccharides, pentosane polysulfate, chondroitin sulfate, dextran sulfate and heparin sulfate.