Claims for Patent: 11,786,548

Summary for Patent: 11,786,548

Title:	Trace element compositions, methods of making and use
Abstract:	Injectable compositions that can be added to parenteral nutrition are provided. In particular, a stable injectable composition is provided which includes water, and at least one of about 800 μg to about 4,000 μg of zinc, about 40 μg to about 400 μg of copper, from about 4 μg to about 90 μg of selenium, or from about 1 μg to about 80 μg of manganese per 1 mL of the injectable composition. Methods of preparing and using of the stable injectable composition are also provided.
Inventor(s):	Gopal Anyarambhatla, Richard Lawrence, Jasmina Marinkovic
Assignee:	American Regent Inc
Application Number:	US17/365,695
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,786,548
Patent Claims:	1. An injectable composition comprising water, about 60 μg of selenium, 3,000 μg of zinc, about 300 μg of copper, and about 55 μg of manganese per 1 mL of the injectable composition, wherein the injectable composition contains 0 μg per 1 mL to about 10 μg per 1 mL of iron, does not contain any vitamins, contains no added chromium and no aluminum or aluminum in an amount not to exceed 6 μg per 1 mL of the injectable composition. 2. The injectable composition of claim 1, wherein the injectable composition comprises 3,000 μg of zinc, 300 μg of copper, 60 μg of selenium, and 55 μg of manganese per 1 mL of the injectable composition. 3. The injectable composition of claim 1, further comprising (i) silicon from about 0.0001 to about 100 μg/mL, magnesium from about 0.0001 to about 50 μg/mL, calcium from about 0.0001 to about 50 μg/mL, boron from about 0.0001 to about 50 μg/mL or a mixture thereof; (ii) silicon from about 0 to about 100 μg/mL, magnesium from about 0 to about 50 μg/mL, calcium from about 0 to about 50 μg/mL, boron from about 0 to about 50 μg/mL or a mixture thereof; or (iii) wherein the zinc is elemental zinc, the copper is elemental copper, the selenium is elemental selenium, the manganese is elemental manganese and the water is sterile water for injection. 4. The injectable composition of claim 1, wherein the composition has a pH of about 1.0 to about 5 and the injectable composition is for use in adult or pediatric human patients. 5. The injectable composition of claim 4, wherein the composition further comprises a pH adjusting agent to adjust the pH. 6. The injectable composition of claim 1, wherein the injectable composition is at least one of a preservative-free composition, a sterile composition, or a ready-to-use injectable aqueous composition. 7. The injectable composition of claim 1, wherein the injectable composition comprises a preservative. 8. The injectable composition of claim 7, wherein the preservative comprises benzyl alcohol in an amount of 0.9% by weight based on a total weight of the injectable composition. 9. The injectable composition of claim 2, wherein the zinc is elemental zinc from zinc sulfate or zinc sulfate heptahydrate, the copper is elemental copper from cupric sulfate or cupric sulfate pentahydrate, the manganese is elemental manganese from manganese sulfate or manganese sulfate monohydrate and the selenium is elemental selenium from selenious acid. 10. The injectable composition of claim 1, wherein the injectable composition is in a multi-dose vial. 11. The injectable composition of claim 10, wherein the multi-dose vial contains 10 mL of the injectable composition. 12. The injectable composition of claim 1, wherein the injectable composition contains about 0.0001 μg/mL to about 0.25 μg/mL of chromium as an impurity. 13. The injectable composition of claim 1, wherein the injectable composition contains about 1 ppm to about 6 μg/mL of aluminum as an impurity. 14. The injectable composition of claim 1, wherein the zinc is zinc sulfate heptahydrate at a dose of about 2.5 to about 7 mg/day, the copper is cupric sulfate pentahydrate at a dose of about 0.3 to about 1.5 mg/day, the manganese is manganese sulfate monohydrate at a dose of about 0.015 to about 0.08 mg/day, and the selenium is selenious acid at a dose of about 20 to about 60 μg/day. 15. An injectable trace element composition comprising water, and as the active ingredients about 7.41 mg of zinc sulfate or zinc sulfate heptahydrate, about 0.75 mg of cupric sulfate or cupric sulfate pentahydrate, about 151 mcg of manganese sulfate or manganese sulfate monohydrate and about 98 mcg of selenious acid per 1 mL of the injectable composition, wherein the injectable composition contains impurities of chromium, aluminum, and iron, wherein the impurities are chromium in an amount not to exceed 1 μg, aluminum in an amount not to exceed 6 μg, and 0 μg to about 10 μg of the iron per 1 mL of the injectable composition. 16. The injectable composition of claim 1, wherein the injectable composition is in a vial. 17. The injectable composition of claim 1, wherein the zinc, copper, selenium, manganese are in elemental or salt form. 18. The injectable composition of claim 5, wherein the pH adjusting agent is at least sodium hydroxide or sulfuric acid. 19. The injectable composition of claim 1, wherein the injectable composition contains less than about 0.25 μg/mL of chromium as an impurity. 20. The injectable composition of claim 1, wherein permitted daily limits (PDL) of the injectable composition do not exceed about 0.4 μg/day of cadmium, about 0.5 μg/day of lead, about 1.5 μg/day of arsenic, about 0.4 μg/day of mercury, about 1 μg/day of cobalt, about 2 μg/day of vanadium, about 4 μg/day of nickel, about 1.6 μg/day of thallium, about 20 μg/day of gold, about 2 μg/day of palladium, about 2 μg/ day of iridium, about 2 μg/day of osmium, about 2 ug/day of rhodium, about 2 μg/day of ruthenium, about 2 μg/day of silver, about 2 ug/day of platinum, about 50 ug/day of lithium, about 18 μg/day of antimony, about 140 μg/day of barium, about 300 μg/day of molybdenum, about 120 μg/ day of tin, about 1 μg/day of chromium, about 6 μg/day of aluminum, about 50 μg/day of boron, about 50 μg/day of calcium, about 10 μg/day of iron, about 94,000 μg/day of potassium, about 50 μg/day of magnesium, about 24,000 μg/day of sodium, about 1 μg/day of tungsten, and/or about 100 μg/day of silicon. 21. The injectable composition of claim 1, wherein the injectable composition contains chromium in an amount not to exceed 1 μg per 1 mL of the injectable composition and the injectable composition contains aluminum in an amount not to exceed 6 μg per 1 mL of the injectable composition. 22. The injectable composition of claim 15, wherein the injectable composition contains no chromium and the injectable composition contains no aluminum. 23. An injectable composition comprising water, active ingredients comprising about 60 μg of selenium, about 3,000 μg of zinc, about 300 μg of copper, and about 55 μg of manganese per 1 mL of the injectable composition, and impurities of chromium, aluminum, and iron, wherein the impurities are chromium in an amount not to exceed 1 μg, aluminum in an amount not to exceed 6 μg, and 0 μg to about 10 μg of the iron per 1 mL of the injectable composition. 24. An injectable composition comprising water, and active ingredients, the active ingredients consisting of about 60 μg of selenium, about 3,000 μg of zinc, about 300 μg of copper, and about 55 μg of manganese per 1 mL of the injectable composition. 25. The injectable composition of claim 24, wherein the active ingredients consists of 60 μg of selenium, 3,000 μg of zinc, 300 μg of copper, and 55 μg of manganese per 1 mL of the injectable composition. 26. An injectable composition comprising water, about 6 μg of selenium, about 1,000 μg of zinc, about 60 μg of copper, and about 3 μg of manganese per 1 mL of the injectable composition, wherein the injectable composition contains 0 μg per 1 mL to about 10 μg per 1 mL of iron, does not contain any vitamins, contains no added chromium and no aluminum or aluminum in an amount not to exceed 6 μg per 1 mL of the injectable composition. 27. An injectable composition comprising water, active ingredients comprising about 6 μg of selenium, about 1,000 μg of zinc, about 60 μg of copper, and about 3 μg of manganese per 1 mL of the injectable composition, and impurities of chromium, aluminum, and iron, wherein the impurities are chromium in an amount not to exceed 1 μg, aluminum in an amount not to exceed 6 μg, and 0 μg to about 10 μg of the iron per 1 mL of the injectable composition. 28. The injectable composition of claim 27, wherein the injectable composition comprises 1000 μg of zinc, 60 μg of copper, 6 μg of selenium and 3 μg of manganese per 1 mL of injectable composition. 29. An injectable composition comprising water, and active ingredients, the active ingredients consisting of about 6 μg of selenium, about 1,000 μg of zinc, about 60 μg of copper, and about 3 μg of manganese per 1 mL of the injectable composition. 30. The injectable composition of claim 29, wherein the active ingredients consist of 6 μg of selenium, 1,000 μg of zinc, 60 μg of copper, and 3 μg of manganese per 1 mL of the injectable composition. 31. An injectable composition comprising water, and active ingredients, the active ingredients consisting of about 2,470 mcg of zinc sulfate or zinc sulfate heptahydrate, about 150 mcg of cupric sulfate or cupric sulfate pentahydrate, about 8.22 mcg of manganese sulfate or manganese sulfate monohydrate and about 9.8 mcg of selenious acid per 1 mL of the injectable composition. 32. The injectable composition of claim 31, wherein the active ingredients consist of 2,470 mcg of zinc sulfate or zinc sulfate heptahydrate, 150 mcg of cupric sulfate or cupric sulfate pentahydrate, 8.22 mcg of manganese sulfate or manganese sulfate monohydrate and 9.8 mcg of selenious acid per 1 mL of the injectable composition. 33. The injectable composition of claim 31, wherein the injectable composition comprises sodium hydroxide or sulfuric acid as a pH adjusting agent. 34. An injectable composition comprising water, and active ingredients, the active ingredients consisting of about 7.41 mg of zinc sulfate or zinc sulfate heptahydrate, about 0.75 mg of cupric sulfate or cupric sulfate pentahydrate, about 151 mcg of manganese sulfate or manganese sulfate monohydrate and about 98 mcg of selenious acid per 1 mL of the injectable composition. 35. The injectable composition of claim 34, wherein the active ingredients consist of 7.41 mg of zinc sulfate or zinc sulfate heptahydrate, 0.75 mg of cupric sulfate or cupric sulfate pentahydrate, 151 mcg of manganese sulfate or manganese sulfate monohydrate and 98 mcg of selenious acid per 1 mL of the injectable composition. 36. The injectable composition of claim 34, wherein the injectable composition comprises sodium hydroxide or sulfuric acid as a pH adjusting agent. 37. The injectable composition of claim 1, wherein the chromium is elemental chromium from chromium chloride. 38. The injectable composition of claim 26, wherein the chromium is elemental chromium from chromium chloride. 39. The injectable composition of claim 26, wherein the injectable composition is for use in pediatric or neonatal human patients. 40. The injectable composition of claim 1, wherein the injectable composition is for use in adult or pediatric human patients. 41. The injectable composition of claim 17, wherein the ratio of elemental copper to elemental zinc is 1:10. 42. The injectable composition of claim 26, wherein the zinc is elemental zinc, the copper is elemental copper, the manganese is elemental manganese and the selenium is elemental selenium. 43. The injectable composition of claim 42, wherein the ratio of elemental selenium to elemental copper is 1:10. 44. The injectable composition of claim 4, wherein the injectable composition comprises a silicon impurity. 45. The injectable composition of claim 4, wherein the injectable composition is in a glass vial or ampule and has a silicon impurity in an amount of not more than 100 μg/mL. 46. The injectable composition of claim 1, wherein the injectable composition is stable for up to two years. 47. The injectable composition of claim 26, wherein the injectable composition is stable for up to two years. 48. The injectable composition of claim 1, wherein the injectable composition has a bacterial endotoxin limit of not more than 50 EU/mL. 49. The injectable composition of claim 26, wherein the injectable composition has a bacterial endotoxin limit of less than 17.50 EU/mL. 50. The injectable composition of claim 26, wherein the injectable composition comprises 1000 μg of zinc, 60 μg of copper, 6 μg of selenium and 3 μg of manganese per 1 mL of injectable composition. 51. The injectable composition of claim 23, wherein the injectable composition comprises 3,000 μg of zinc, 300 μg of copper, 60 μg of selenium, and 55 μg of manganese per 1 mL of the injectable composition. 52. The injectable composition of claim 23, wherein the zinc is elemental zinc from zinc sulfate or zinc sulfate heptahydrate, the copper is elemental copper from cupric sulfate or cupric sulfate pentahydrate, the manganese is elemental manganese from manganese sulfate or manganese sulfate monohydrate and the selenium is elemental selenium from selenious acid. 53. The injectable composition of claim 26, wherein the zinc is elemental zinc from zinc sulfate or zinc sulfate heptahydrate, the copper is elemental copper from cupric sulfate or cupric sulfate pentahydrate, the manganese is elemental manganese from manganese sulfate or manganese sulfate monohydrate and the selenium is elemental selenium from selenious acid. 54. The injectable composition of claim 26, wherein the injectable composition is in a vial. 55. The injectable composition of claim 15, wherein the injectable composition is for use in adult or pediatric human patients. 56. The injectable composition of claim 23, wherein the injectable composition is for use in adult or pediatric human patients. 57. The injectable composition of claim 27, wherein the injectable composition is for use in pediatric or neonatal human patients. 58. The injectable composition of claim 31, wherein the injectable composition is for use in pediatric or neonatal human patients.