ANHYDROUS SODIUM THIOSULFATE AND FORMULATIONS THEREOF
Described herein is anhydrous sodium thiosulfate, methods for synthesizing anhydrous sodium thiosulfate, pharmaceutical compositions thereof, and methods of treating ototoxicity. Anhydrous sodium thiosulfate is synthesized from sodium sulfite, sulfur, and cetylpyridinium chloride. The anhydrous sodium thiosulfate is formulated into a pharmaceutical composition comprising a buffer and solvent. These compositions are useful for eliminating or reducing ototoxicity in pediatric patients receiving platinum-based chemotherapeutics.
1 . A pharmaceutical composition comprising a sodium thiosulfate at a concentration between about 0.3 M and about 0.6 M and further comprising a buffer at a concentration between about 0.01 M and about 0.05 M wherein the buffer is selected from carbonate, maleate, citrate, isocitrate, succinate, aspartate, and glutamate.
2 . The pharmaceutical composition of claim 1 , wherein the sodium thiosulfate is aqueous anhydrous sodium thiosulfate.
3 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a base.
4 . The pharmaceutical composition of claim 3 , wherein the base is sodium hydroxide.
5 . The pharmaceutical composition of claim 1 , wherein the buffer is carbonate.
6 . The pharmaceutical composition of claim 1 , wherein the buffer is aspartate.
7 . The pharmaceutical composition of claim 1 , wherein the buffer is glutamate.
8 . The pharmaceutical composition of claim 1 , wherein the buffer is citrate.
9 . The pharmaceutical composition of claim 1 , wherein the buffer is isocitrate.
10 . The pharmaceutical composition of claim 1 , wherein the buffer is maleate.
11 . The pharmaceutical composition of claim 1 , wherein the buffer is succinate.
12 . The pharmaceutical composition of claim 1 , wherein the concentration of the sodium thiosulfate is about 0.5 M.
13 . A pharmaceutical composition comprising a sodium thiosulfate at a concentration between about 0.3 M and about 0.6 M and further comprising a buffer at a concentration between about 0.01 M and about 0.05 M wherein the buffer is selected from sulfate, formate, acetate, propionate, butanoate, lactate, pyruvate, aconitate, α-ketoglutarate, fumarate, malate, and oxaloacetate.
14 . The pharmaceutical composition of claim 13 , wherein the buffer is sulfate.
15 . The pharmaceutical composition of claim 13 , wherein the buffer is formate.
16 . The pharmaceutical composition of claim 13 , wherein the buffer is acetate.
17 . The pharmaceutical composition of claim 13 , wherein the buffer is propionate.
18 . The pharmaceutical composition of claim 13 , wherein the buffer is butanoate.
19 . The pharmaceutical composition of claim 13 , wherein the buffer is lactate.
20 . The pharmaceutical composition of claim 13 , wherein the buffer is pyruvate.
21 . The pharmaceutical composition of claim 13 , wherein the buffer is aconitate.
22 . The pharmaceutical composition of claim 13 , wherein the buffer is α-ketoglutarate.
23 . The pharmaceutical composition of claim 13 , wherein the buffer is fumarate.
24 . The pharmaceutical composition of claim 13 , wherein the buffer is malate.
25 . The pharmaceutical composition of claim 13 , wherein the buffer is oxaloacetate.
26 . The pharmaceutical composition of claim 13 , wherein the concentration of the sodium thiosulfate is about 0.5 M.