Sodium thiosulfate-containing pharmaceutical compositions
Provided herein are pharmaceutically acceptable sodium thiosulfate and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-purgeable organic carbon in a sodium thiosulfate-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium thiosulfate. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium thiosulfate.
1. A method for treating vascular calcification, comprising administering to a subject having vascular calcification, an anti-diabetic agent in combination with pharmaceutical grade sodium thiosulfate pentahydrate, wherein the pharmaceutical grade sodium thiosulfate pentahydrate contains no greater than about 10 ppm of non-purgeable organic carbon, contains no greater than about 0.05 ppm of mercury, contains no greater than about 2 ppm of aluminum, contains no greater than about 0.003% by weight of selenium, contains no less than about 98% by weight and no greater than about 102% by weight of sodium thiosulfate on an anhydrous basis measured by ion chromatography, has a water content between 32% and 37% by weight, has a heavy metal content of no greater than about 10 ppm, contains no greater than about 200 ppm of chloride, contains no greater than about 0.001% by weight of sulfide, contains no greater than about 0.002% by weight of iron, contains no greater than about 0.01% by weight of calcium, contains no greater than about 0.005% by weight of potassium, contains no greater than about 0.1% of sulfite, contains no greater than about 0.5% of sulfate, contains no greater than about 3 ppm of arsenic, contains no greater than about 0.001% by weight of lead, has total aerobic count of microbial load of no greater than about 100 CFU/g, has total yeast and mold count of no greater than about 20 CFU/g, contains no greater than about 0.02 EU/mg of bacterial endotoxins, contains no greater than about 0.002% by weight of nitrogen compounds, contains no greater than about 0.005% by weight of insoluble matter, contains no greater than 0.01% by weight of residual anti-caking agent, and contains no greater than ICH Q3C (R3) limits of organic volatile impurities, wherein a 10% aqueous solution of the pharmaceutical grade sodium thiosulfate pentahydrate at 25° C. is colorless and has a pH between about 6.0 and about 8.0, and wherein the pharmaceutical grade sodium thiosulfate pentahydrate is odorless crystals.
2. The method of claim 1 , wherein the anti-diabetic agent is a biguanide, a glucosidase inhibitor, insulin, a meglitinide, a sulfonylurea, a thiazolidinedione or a PPAR-gamma agonist.
3. The method of claim 2 , wherein the biguanide is metformin.
4. The method of claim 2 , wherein the glucosidase inhibitor is acarbose.
5. The method of claim 2 , wherein the meglitinide is repaglinide.
6. The method of claim 2 , wherein the sulfonylurea is glimepiride, glyburide or glipizide.
7. The method of claim 2 , wherein the thiazolidinedione is troglitazone, rosiglitazone or pioglitazone.
8. The method of claim 1 , wherein the administration is oral.
9. The method of claim 1 , wherein the administration is topical.
10. The method of claim 1 , wherein the administration is intradermal, dermal or transdermal.
11. The method of claim 1 , wherein the administration is intravenous or subcutaneous.
12. The method of claim 1 , wherein the administration is rectal.
13. The method of claim 1 , wherein the vascular calcification is caused by diabetes.
14. A method for treating atherosclerosis, comprising administering to a subject having atherosclerosis, an anti-diabetic agent in combination with pharmaceutical grade sodium thiosulfate pentahydrate, wherein the pharmaceutical grade sodium thiosulfate pentahydrate contains no greater than about 10 ppm of non-purgeable organic carbon, contains no greater than about 0.05 ppm of mercury, contains no greater than about 2 ppm of aluminum, contains no greater than about 0.003% by weight of selenium, contains no less than about 98% by weight and no greater than about 102% by weight of sodium thiosulfate on an anhydrous basis measured by ion chromatography, has a water content between 32% and 37% by weight, has a heavy metal content of no greater than about 10 ppm, contains no greater than about 200 ppm of chloride, contains no greater than about 0.001% by weight of sulfide, contains no greater than about 0.002% by weight of iron, contains no greater than about 0.01% by weight of calcium, contains no greater than about 0.005% by weight of potassium, contains no greater than about 0.1% of sulfite, contains no greater than about 0.5% of sulfate, contains no greater than about 3 ppm of arsenic, contains no greater than about 0.001% by weight of lead, has total aerobic count of microbial load of no greater than about 100 CFU/g, has total yeast and mold count of no greater than about 20 CFU/g, contains no greater than about 0.02 EU/mg of bacterial endotoxins, contains no greater than about 0.002% by weight of nitrogen compounds, contains no greater than about 0.005% by weight of insoluble matter, contains no greater than 0.01% by weight of residual anti-caking agent, and contains no greater than ICH Q3C (R3) limits of organic volatile impurities, wherein a 10% aqueous solution of the pharmaceutical grade sodium thiosulfate pentahydrate at 25° C. is colorless and has a pH between about 6.0 and about 8.0, and wherein the pharmaceutical grade sodium thiosulfate pentahydrate is odorless crystals.
15. The method of claim 14 , wherein the anti-diabetic agent is a biguanide, a glucosidase inhibitor, insulin, a meglitinide, a sulfonylurea, a thiazolidinedione or a PPAR-gamma agonist.
16. The method of claim 15 , wherein the biguanide is metformin.
17. The method of claim 15 , wherein the glucosidase inhibitor is acarbose.
18. The method of claim 15 , wherein the meglitinide is repaglinide.
19. The method of claim 15 , wherein the sulfonylurea is glimepiride, glyburide or glipizide.
20. The method of claim 15 , wherein the thiazolidinedione is troglitazone, rosiglitazone or pioglitazone.
21. The method of claim 14 , wherein the administration is oral.
22. The method of claim 14 , wherein the administration is topical.
23. The method of claim 14 , wherein the administration is intradermal, dermal or transdermal.
24. The method of claim 14 , wherein the administration is intravenous or subcutaneous.
25. The method of claim 14 , wherein the administration is rectal.
26. The method of claim 14 , wherein the atherosclerosis is caused by diabetes.