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Fluid therapy with L-lactate and/or pyruvate anions

Imported: 24 Feb '17 | Published: 28 Sep '04

Richard L. Veech

USPTO - Reissues

Abstract

Electrolyte solutions are provided which are useful in electrolyte and fluid therapy, parenteral nutrition and dialysis. The Na:Cl ratio is normalized, plasma and cellular pH are normalized and cellular cofactor ratios are normalized in a manner which decreases toxicity over prior art solutions.

Claims

1. A solution for rehydration, electrolyte replacement, and nutrition comprising water having dissolved therein the following components in the respective quantities indicated:

provided that in any given said solution,

2. A solution as defined in claim 1 wherein the solution further contains dissolved carbon dioxide.

3. A solution as defined in claim 1 wherein the solution further contains both bicarbonate anion and dissolved carbon dioxide.

4. A solution for dialysis therapy comprising water having dissolved therein the following components in the respective quantities indicated:

provided that in any given said solution,

5. The solution of claim 4 wherein said solution additionally contains from about 20 to 55 mM of bicarbonate anions and wherein said solution also contains a sufficient portion of at least one of said pyruvate

, d-beta- D--hydroxybutyrate

and acetoacetate

anions which are derived at least in part from the addition to said solution of, respectively, at least one of pyruvic acid, d-beta- D--hydroxybutyric acid and/or acetoacetic acid in a total amount which is sufficient to produce pH in the range from about 5 to 8.2, and said solution contains sufficient nonionic dissolved nutrients to achieve a milliosmolarity of from about 250 to 550 mOsmole/Liter.

6. The solution of claim 4 wherein said solution additionally contains from about 20 to 55 mM of bicarbonate anions and wherein said solution also contains a sufficient portion of at least one of said pyruvate

, d-beta- D--hydroxy-butyrate

and acetoacetate

anions derived from the addition to said solution of, respectively, at least one of pyruvic acid, d-beta- D--hydroxybutyric acid and/or acetoacetic acid in a total amount which is sufficient to produce pH in the range of from about 5.5 to 7.5, and said solution also contains sufficient nonionic dissolved nutrients to achieve a solution milliosmolarity of from about 260 to 550 mOsmoles/Liter.

7. A solution containing at least one anion species selected from the group consisting of pyruvate in an amount so that the concentration of pyruvate

anions in the fluid is in the range of about 0.01 to 40 millimole per liter, D--hydroxybutyrate

, and acetoacetate

, and at least one cation selected from the group consisting of sodium

+, potassium

+, magnesium

2+, calcium

2+ and ammonium

+, the total concentration of all said anions in said solution being in the range from about 0.01 to 2400 millimoles per liter wherein the solution further comprises one or more of

8. A solution as defined in claim 7 wherein the solution further contains dissolved carbon dioxide.

9. A solution as defined in claim 7, wherein the solution further contains both bicarbonate anion and dissolved carbon dioxide.

10. A solution of claim 7 wherein the Ph is the range of 5 to 8.2.

11. A solution of claim 7 additionally containing chlorine anion in the range of 0.01 to 2000 millimoles per liter.

12. A solution of claim 7 additionally containing glucose in the range of 0.01 to 540 millimoles per liter.

13. A solution for enteral or parenteral administration to a patient comprising: an electrically neutral aqueous solution of at least one cation and at least one anion, wherein the sole monoanionic organic metabolic anion present in said aqueous solution is pyruvate anion, present in an amount of from about 0.1 to about 40 millimoles per liter of said aqueous solution, said aqueous solution containing substantially no D-lactate or acetate anions, and said aqueous solution having a pH of from about 5 to about 8.2, wherein the solution further comprises one or more of

14. A solution as defined in claim 13, further comprising from about 20 to about 55 millimoles per liter of bicarbonate anion.

15. A solution as defined in claim 13, further comprising from about 0.01 to about 2000 millimoles per liter of chloride ion.

16. A solution as defined in claim 13, further comprising at least one nonionic dissolved nutrient in an amount sufficient to provide a solution osmolarity in said aqueous solution of from about 250 to about 550 milliosmoles per liter.

17. A solution as defined in claim 13, wherein said at least one cation is selected from the group consisting of sodium ions, potassium ions, calcium ions, magnesium ions, and mixtures of sodium ions with any of potassium ions, calcium ions and magnesium ions.

18. A solution for enteral or parenteral administration to a patient comprising: an electrically neutral aqueous solution of at least one cation and at least one anion, wherein the sole monoanionic organic metabolic anion present in said aqueous solution is D--hydroxybutyrate anion, present in an amount of from about

0.

1 to about

55

0.

01 to about

2400 millimoles per liter of said aqueous solution, said aqueous solution containing substantially no D-lactate or acetate anions, and said aqueous solution having a pH of from about 5 to about 8.2, wherein the solution further comprises one or more of

19. A solution as defined in claim 18, further comprising from about 20 to about 55 millimoles per liter of bicarbonate anion.

20. A solution as defined in claim 18, further comprising from about 0.01 to about 2000 millimoles per liter of chloride ion.

21. A solution as defined in claim 18, further comprising at least one nonionic dissolved nutrient in an amount sufficient to provide a solution osmolarity in said aqueous solution of from about 250 to about 550 milliosmoles per liter.

22. A solution as defined in claim 18, wherein said at least one cation is selected from the group consisting of sodium ions, potassium ions, calcium ions, magnesium ions, and mixtures of sodium ions with any of potassium ions, calcium ions and magnesium ions.

23. A solution for enteral or parenteral administration to a patient comprising: an electrically neutral aqueous solution of at least one cation and at least one anion, wherein the sole monoanionic organic metabolic anion present in said aqueous solution is acetoacetate anion, present in an amount of from about 0.1 to about 55 millimoles per liter of said aqueous solution, said aqueous solution containing substantially no D-lactate or acetate anions, and said aqueous solution having a pH of from about 5 to about 8.2, wherein the solution further comprises one or more of

24. A solution as defined in claim 23, further comprising from about 20 to about 55 millimoles per liter of bicarbonate anion.

25. A solution as defined in claim 23, further comprising from about 0.01 to about 2000 millimoles per liter of chloride ion.

26. A solution as defined in claim 23, further comprising at least one nonionic dissolved nutrient in an amount sufficient to provide a solution osmolarity in said aqueous solution of from about 250 to about 550 milliosmoles per liter.

27. A solution as defined in claim 23, wherein said at least one cation is selected from the group consisting of sodium ions, potassium ions, calcium ions, magnesium ions, and mixtures of sodium ions with any of potassium ions, calcium ions and magnesium ions.

28. A solution for rehydration, electrolyte replacement, and nutrition comprising water having dissolved therein the following components in the respective quantities indicated:

and as a sole monoanionic organic metabolic anion present in said solution, a monoanionic organic metabolic anion selected from the group consisting of pyruvate, D--hydroxybutyrate and acetoacetate, said organic metabolic anion being present in an amount of from about 0.1 to about 55 millimoles per liter of solution, except for pyruvate which may be present in an amount of from about 0.1 to about 40 millimoles per liter of said solution, said solution containing substantially no D-lactate or acetate anions, the total amount of said cations present in said solution being sufficient to provide electrical neutrality and said solution having a pH of from about 6.0 to about 7.5.

29. A solution for dialysis therapy comprising water having dissolved therein the following components in the respective quantities indicated:

and as a sole monoanionic organic metabolic anion present in said solution, a monoanionic organic metabolic anion selected from the group consisting of pyruvate, D--hydroxybutyrate and acetoacetate, said organic metabolic anion being present in an amount of from about 0.1 to about 55 millimoles per liter of solution, except for pyruvate which may be present in an amount of from about 0.1 to about 40 millimoles per liter of said solution, said solution containing substantially no D-lactate or acetate anions, the total amount of said cations present in said solution being sufficient to provide electrical neutrality and said solution having a pH of from about 5 to about 8.2.

30. A solution for rehydration, electrolyte replacement, and nutrition comprising water having dissolved therein the following components in the respective quantities indicated:

wherein the solution further comprises one or more of