Claims for Patent: 9,687,506

Summary for Patent: 9,687,506

Title:	Sodium nitrite-containing pharmaceutical compositions
Abstract:	Provided herein are pharmaceutically acceptable sodium nitrite and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-volatile organic carbon in a sodium nitrite-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium nitrite. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium nitrite.
Inventor(s):	Sherman; Craig (Scottsdale, AZ), Lepine; Anthony James (Greendale, WI), Smith; Catherine Marie (Grafton, WI), Wirtz; Kevin Robert (Belgium, WI), Schulze; Erich (Mission Viejo, CA)
Assignee:	Hope Medical Enterprises, Inc. (Scottsdale, AZ)
Application Number:	15/251,015
Patent Claims:	1. A pharmaceutical composition comprising sodium nitrite and one or more pharmaceutically acceptable carriers or excipients, wherein the sodium nitrite contains no greater than 0.02% by weight of sodium carbonate, contains no greater than 10 ppm of an anti-caking agent, has a loss on drying of no greater than 0.25% by weight, wherein the water content is no greater than 0.5% by weight, wherein the heavy metal content is no greater than 10 ppm, contains no greater than 0.4% by weight of sodium nitrate, contains no greater than 0.005% by weight of insoluble matter, contains no greater than 0.005% by weight of chloride, contains no greater than 0.01% by weight of sulfate, contains no greater than 0.001% by weight of iron, contains no greater than 0.01% by weight of calcium, contains no greater than 0.005% by weight of potassium, contains no greater than 0.05 ppm of mercury, contains no greater than 2 ppm of aluminum, contains no greater than 3 ppm of arsenic, contains no greater than 0.003% by weight of selenium, contains no greater than 5000 ppm of ethanol, contains no greater than 3000 ppm methanol, wherein the total non-volatile organic carbon content is no greater than 10 ppm, and contains no greater than 0.25 EU/mg of bacterial endotoxins, wherein the pharmaceutical composition is formulated for intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular, intrasynovial, intravesical, or subcutaneous administration. 2. The pharmaceutical composition of claim 1, wherein the sodium nitrite contains no less than about 98% by weight of sodium nitrite. 3. The pharmaceutical composition of claim 1, wherein the sodium nitrite contains no less than about 99.8% by weight of sodium nitrite as measured by Ion Chromatography analysis. 4. The pharmaceutical composition of claim 3, wherein the sodium nitrite is a white solid. 5. The pharmaceutical composition of claim 4, wherein a 10% aqueous solution of the sodium nitrite at 25.degree. C. has a pH value between 8 and 9. 6. The pharmaceutical composition of claim 5, which has total aerobic count of microbial load of no greater than about 100 CFU/g and has total yeast and mold count of no greater than about 20 CFU/g. 7. The pharmaceutical composition of claim 1, wherein the composition is formulated as a single dosage form. 8. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient is water. 9. The pharmaceutical composition of claim 1, further comprising one or more pH adjusting agents. 10. The pharmaceutical composition of claim 9, further comprising one or more isotonic agents. 11. The pharmaceutical composition of claim 1, formulated for intravenous administration. 12. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intravenous injection, infusion, or implantation. 13. The pharmaceutical composition of claim 1, formulated for intraarterial administration. 14. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intraarterial injection, infusion, or implantation. 15. The pharmaceutical composition of claim 1, formulated for intraperitoneal administration. 16. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intraperitoneal injection, infusion, or implantation. 17. The pharmaceutical composition of claim 1, formulated for intrathecal administration. 18. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intrathecal injection, infusion, or implantation. 19. The pharmaceutical composition of claim 1, formulated for intraventricular administration. 20. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intraventricular injection, infusion, or implantation. 21. The pharmaceutical composition of claim 1, formulated for intraurethal administration. 22. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intraurethral injection, infusion, or implantation. 23. The pharmaceutical composition of claim 1, formulated for intrasternal administration. 24. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intrasternal injection, infusion, or implantation. 25. The pharmaceutical composition of claim 1, formulated for intracranial administration. 26. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intracranial injection, infusion, or implantation. 27. The pharmaceutical composition of claim 1, formulated for intramuscular administration. 28. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intramuscular injection, infusion, or implantation. 29. The pharmaceutical composition of claim 1, formulated for intrasynovial administration. 30. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intrasynovial injection, infusion, or implantation. 31. The pharmaceutical composition of claim 1, formulated for intravesical administration. 32. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for intravesical injection, infusion, or implantation. 33. The pharmaceutical composition of claim 1, formulated for administration by subcutaneous injection. 34. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a sterile aqueous solution intended for subcutaneous injection, infusion, or implantation. 35. A method for treating cyanide poisoning, comprising sequentially administering intramuscularly to a subject having cyanide poisoning: (1) a therapeutically effective amount of a sterile aqueous solution comprising the pharmaceutical composition of claim 1; and (2) a therapeutically effective amount of a sterile aqueous solution comprising pharmaceutical grade sodium thiosulfate pentahydrate. 36. A kit that includes: (1) a single unit dosage form comprising pharmaceutical grade sodium nitrite, wherein said pharmaceutical grade sodium nitrite contains no greater than 0.02% by weight of sodium carbonate, contains no greater than 10 ppm of an anti-caking agent, has a loss on drying of no greater than 0.25% by weight, wherein the water content is no greater than 0.5% by weight, wherein the heavy metal content is no greater than 10 ppm, contains no greater than 0.4% by weight of sodium nitrate, contains no greater than 0.005% by weight of insoluble matter, contains no greater than 0.005% by weight of chloride, contains no greater than 0.01% by weight of sulfate, contains no greater than 0.001% by weight of iron, contains no greater than 0.01% by weight of calcium, contains no greater than 0.005% by weight of potassium, contains no greater than 0.05 ppm of mercury, contains no greater than 2 ppm of aluminum, contains no greater than 3 ppm of arsenic, contains no greater than 0.003% by weight of selenium, contains no greater than 5000 ppm of ethanol, contains no greater than 3000 ppm methanol, wherein the total non-volatile organic carbon content is no greater than 10 ppm, and contains no greater than 0.25 EU/mg of bacterial endotoxins; and (2) a single unit dosage form comprising sodium thiosulfate pentahydrate, wherein said sodium thiosulfate pentahydrate contains no greater than 8 ppm of non-purgeable organic carbon, contains no greater than 0.05 ppm of mercury, contains no greater than 2 ppm of aluminum, contains no greater than 0.003% by weight of selenium, contains no less than 98% 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 10 ppm, contains no greater than 200 ppm of chloride, contains no greater than 0.001% by weight of sulfide, contains no greater than 0.002% by weight of iron, contains no greater than 0.01% by weight of calcium, contains no greater than 0.005% by weight of potassium, contains no greater than 0.1% of sulfite, contains no greater than 0.5% of sulfate, contains no greater than 3 ppm of arsenic, contains no greater than 0.001% by weight of lead, has total aerobic count of microbial load of no greater than 100 CFU/g, has total yeast and mold count of no greater than 20 CFU/g, contains no greater than 0.02 EU/mg of bacterial endotoxins, contains no greater than 0.002% by weight of nitrogen compounds, contains no greater than 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 solid sodium thiosulfate pentahydrate at 25.degree. C. is colorless and has a pH between 6.0 and 8.0, and wherein the solid sodium thiosulfate pentahydrate is odorless crystals.