STRONTIUM BASED COMPOSITIONS AND FORMULATIONS FOR PAIN, PRURITUS, AND INFLAMMATION
Therapeutically-active compositions and formulations for treating pain, pruritus, irritation, inflammation, and tissue damage due to the irritation and inflammation, and therapeutically-active compositions and formulations for wound management, including wounds that are at high risk for infection. Strontium and beta hydroxybutyrate based compositions and formulations which can be topically applied.
1 . A composition comprising a complex of:
a divalent cationic strontium moiety;
a cysteine-based moiety selected from the group consisting of cystine, N-acetyl cysteine, N-acetyl cysteinate, N-acetyl cystine, N,S-diacetylcysteine, and esters thereof; and
a beta hydroxybutyrate moiety;
wherein the cysteine-based anti-oxidant and the beta hydroxybutyrate moiety are conjugated together by a cleavable bond.
2 . The composition of claim 1 , wherein the cysteine-based anti-oxidant moiety is N-acetyl cysteine or an ester thereof.
3 . The composition of claim 1 , wherein the strontium moiety is a strontium salt 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 composition of claim 1 , wherein the cleavable bond is selected from the group consisting of a peptide bond, an ester bond, a thioester bond, an enzymatically cleavable bond, a disulfide bond, and a pH dependent bond.
5 . The composition of claim 1 , wherein the cleavable bond is a thioester bond.
6 . The composition of claim 1 , further comprising a polymer.
7 . The composition of claim 6 , wherein the polymer is selected from the group consisting of polyvinylpyrrolidone, cyclodextrins, carrageenan, alginic acid, xanthan gum, sulfated polysaccharides, pentosan polysulfate, chondroitin sulfate, dextran sulfate and heparin sulfate.
8 . The composition of claim 1 , comprising a complex of divalent cationic strontium, N-acetylcysteine or an ester thereof and beta hydroxybutyrate, wherein the N-acetylcysteine or an ester thereof and the beta hydroxybutyrate are conjugated together by a thioester bond formed by a sulfhydryl group of the N-acetylcysteine or an ester thereof and a carboxyl group of the beta hydroxybutyrate moiety.
9 . A formulation comprising the composition of claim 1 and at least one pharmaceutically acceptable excipient.
10 . The formulation of claim 9 , wherein the formulation is configured for topical administration.
11 . The formulation of claim 9 , wherein the formulation is configured for oral or systemic administration.
12 . The formulation of claim 9 , wherein the formulation is configured for oral ingestion.
13 . The formulation of claim 9 , further comprising a polymer.
14 . The formulation of claim 13 , wherein the polymer is a neutral or anionic polymer.
15 . The formulation of claim 14 , wherein the neutral polymer is polyvinylpyrrolidone.
16 . The formulation of claim 15 , wherein the polyvinylpyrrolidone is chemically modified by derivatization and/or crosslinking.
17 . The formulation of claim 13 , wherein the polymer is configured for ionic association with the complex and facilitates controlled release of the divalent cationic strontium.
18 . The formulation of claim 13 , wherein the polymer is configured for minimizing osmolarity.
19 . The formulation of claim 9 , further comprising at least one aromatic amino acid selected from the group consisting of histidine, tyrosine, phenylalanine and tryptophan.
20 . The formulation of claim 19 , wherein the at least one aromatic amino acid is an L-isomer.
21 . A method of treating pain, comprising topically administering the composition of claim 1 to a patient in need thereof.
22 . A method of treating pruritus, comprising topically administering the composition of claim 1 to a patient in need thereof.