COMBINATION OF A URINARY ACIDIFIER AND A CALCIUM PHOSPHATE CRYSTALLISATION INHIBITOR FOR THE TREATMENT OR PREVENTION OF RENAL LITHIASIS

Abstract

The present invention is related to the use of a separate, sequential or simultaneous combination of at least one urinary acidifier with at least one calcium phosphate crystallization inhibitor for urine acidification, and thus preventing the pH at which supersaturation of calcium phosphate is produced and consequently, renal lithiasis.

Claims

1. Use of a preparation comprising at least one urinary acidifier combined sequentially, simultaneously or separately with at least one calcium phosphate crystallization inhibitor, in the manufacture of a medicament.

2. Use of a preparation comprising at least one urinary acidifier combined sequentially, simultaneously or separately with at least one calcium phosphate crystallization inhibitor, in the manufacture of a medicament for the treatment or prevention of renal lithiasis.

3. The use according to claim 1 wherein the urinary acidifier is selected from a portion or an extract of the plant species Vaccinum, pharmaceutically acceptable ammonium salts, arginine or any of its pharmaceutically acceptable salts, cysteine or any of its pharmaceutically acceptable salts, phenazopyridine or any of its pharmaceutically acceptable salts, methionine or any of its pharmaceutically acceptable salts or mixtures thereof.

4. The use according to claim 3 wherein the urinary acidifier is selected from cranberry, ammonium chloride, L-arginine, L-cysteine or mixtures thereof.

5. The use according to claim 1 wherein the crystallization inhibitor is phytic acid or any of its pharmaceutically acceptable salts.

6. The use according to claim 5 wherein the pharmaceutically acceptable salts of phytic acid are selected from sodium phytate, potassium phytate, calcium phytate, magnesium phytate, zinc phytate, calcium-magnesium phytate or combinations of the same.

7. The use according to claim 5 wherein phytic acid or its salts are derived from a portion of a plant species rich in phytic acid or its salts, or from a plant extract of said plant species.

8. The use according to claim 2, wherein the medicament is in a form suitable for oral, parenteral, enteral or intravenous administration.

9. The use according to claim 2 wherein renal lithiasis is calcium oxalate lithiasis induced by calcium phosphate.

10. The use according to claim 2 wherein renal lithiasis is a mixed calcium oxalate/calcium phosphate lithiasis induced by calcium phosphate.

11. Composition comprising at least one urinary acidifier and at least one calcium phosphate crystallization inhibitor.

12. Composition according to claim 11 wherein the urinary acidifier is selected from a portion or an extract of the plant species Vaccinum, pharmaceutically acceptable ammonium salts, arginine or any of its pharmaceutically acceptable salts, cysteine or any of its pharmaceutically acceptable salts, phenazopyridine or any of its pharmaceutically acceptable salts.

13. Composition according to claim 12 wherein the urinary acidifier is selected from cranberry, ammonium chloride, L-arginine, L-cysteine or mixtures thereof.

14. Composition according to claim 11 wherein the crystallization inhibitor is phytic acid or any of its pharmaceutically acceptable salts.

15. Composition according to claim 14 wherein the pharmaceutically acceptable salts of phytic acid are selected from sodium phytate, potassium phytate, calcium phytate, magnesium phytate, zinc phytate and calcium-magnesium phytate.

16. Composition according to claim 14 wherein phytic acid or its salts are derived from a portion of a plant species rich in phytic acid or its salts, or from a plant extract of said plant species.

17. Composition according to claim 11, wherein the composition is a pharmaceutical composition or a nutraceutical or a functional food.

18. Use of the composition described according to claim 11 in the preparation of a medicament.

19. Use of the composition described according to claim 11 in the preparation of a medicament for the treatment and/or prevention of renal lithiasis.

20. Kit comprising at least one urinary acidifier and at least one calcium phosphate crystallization inhibitor.

21. Kit according to claim 20 wherein the urinary acidifier is selected from a portion or an extract of the plant species Vaccinum, pharmaceutically acceptable ammonium salts, arginine or any of its pharmaceutically acceptable salts, cysteine or any of its pharmaceutically acceptable salts, phenazopyridine or any of its pharmaceutically acceptable salts.

22. Kit according to claim 21 wherein the urinary acidifier is selected from cranberry, ammonium chloride, L-arginine, L-cysteine or mixtures thereof.

23. Kit according to claim 20 wherein the crystallization inhibitor is phytic acid or any of its pharmaceutically acceptable salts.

24. Kit according to claim 23 wherein the pharmaceutically acceptable salts of phytic acid are selected from sodium phytate, potassium phytate, calcium phytate, magnesium phytate, zinc phytate and calcium-magnesium phytate.

25. Kit according to claim 23 wherein phytic acid or its salts are derived from a portion of a plant species rich in phytic acid or its salts, or from a plant extract of said plant species.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0049] FIG. 1. It shows the graphical representation of the induction times (in minutes) for a 15 mM phosphate and 3 mM calcium solution, in artificial urine, at different pH and phytate concentration.

[0050] FIG. 2. It shows the graphical representation of the induction times (in minutes) against a phytate concentration (M), according to the pH.

EXAMPLES

[0051] Next, the invention will be illustrated by means of tests performed by the inventors that reveal the effectiveness of the product of the invention.

Example 1: Measurement of the Times of Crystallization of Calcium Phosphate

[0052] From a 15 mM phosphate ion and 3 mM calcium ion solution in artificial urine, the induction times for the crystallization of calcium phosphate have been calculated at different pH and phytate concentration. The artificial urine had no magnesium since it is shown that the magnesium ion is a calcium phosphate crystallization inhibitor. Table 1 shows said induction times, which as it can be clearly seen (FIG. 1) increase with the decrease of the pH and with the increase of the phytate concentration. Thus, while at pH 6.75, the calcium phosphate solution (without inhibitor) takes 1 minute to crystallize, with 1 M phytate it takes 2 minutes (the delay in the induction time at this pH value is 1 minute, for 1 M phytate). However, when the pH decreases to 6.60, the calcium phosphate solution (without inhibitor) takes 6 minutes to crystallize, while with 1 M phytate it takes 33 minutes (the delay in the induction time at this pH value is 27 minutes, for 1 M phytate). Thus, for the same amount of inhibitor there is a significant increase of the crystallization time when the value of the pH of the solution decreases.

TABLE-US-00002 TABLE 1 induction times (in minutes) for a 15 mM phosphate and 3 mM calcium solution, in artificial urine, at different pH and phytate concentration. t (min) t (min) t (min) pH = 6.75 pH = 6.65 pH = 6.60 0 M phytate 1 3 6 0.5 M phytate 1 4 12 1.0 M phytate 2 6 33