Composition containing phytic acid, magnesium and polyphenols for the treatment or prevention of renal lithiasis

Abstract

The present invention is related to a composition comprising phytic acid or a phytate salt, magnesium in the form of salt, hydroxide or oxide and optionally at least one polyphenol. These components may be in isolated form or be part of an enriched plant extract. The invention is also related to the use of this composition for the treatment of renal lithiasis, preferably calcium or calcium oxalate lithiasis, either in the form of a medicament, a nutraceutical or functional food or food supplement.

Claims

1. A method for treating a patient with renal lithiasis, comprising: administering to the patient a composition comprising phytic acid or a salt thereof, magnesium oxide, and magnesium stearate, wherein the composition comprises between 25% and 40% by weight of the magnesium compounds; and wherein the renal lithiasis is oxalocalcium renal lithiasis, and wherein the oxalocalcium renal lithiasis is related to the crystallization of calcium oxalate, and wherein the composition synergistically inhibits crystallization of calcium oxalate.

2. The method of claim 1, wherein administration of the composition reduces the risks and improve the health status of the patient in relation to the crystallization of calcium oxalate.

3. The method of claim 1, wherein the composition is in a suitable dosage for administration of between 500 mg/day and 1,000 mg/day.

4. The method of claim 1, wherein the composition further comprises at least one polyphenol.

5. The method of claim 4, wherein the at least one polyphenol is selected from the group consisting of: epicatechin, catechin, gallocatechin, epigallocatechin, quercetin, resveratrol, gallic acid and tannic acid.

6. The method of claim 4, wherein the at least one polyphenol is in the form of plant extract from grape seed.

7. The method of claim 1, wherein the composition comprises between 40% and 50% by weight of phytic acid or its salt.

8. The method of claim 4, wherein the composition comprises between 10% and 30% by weight of polyphenols.

9. The method of claim 1, wherein the composition further comprises lactose, sucrose, talc, cellulose, calcium salts, gelatin or fatty acids.

10. The method of claim 1, wherein the composition is in the form of a pharmaceutical composition, functional food, a nutraceutical product, or a food supplement.

11. A method for treating a patient with renal lithiasis, comprising: administering to the patient a composition comprising (i) phytic acid or a salt thereof, and (ii) a magnesium compound selected from the group consisting of: magnesium oxide, magnesium hydroxide, magnesium citrate, magnesium stearate, magnesium carbonate, magnesium chloride, magnesium sulfate, and a combination thereof; wherein the composition comprises between 25% and 40% by weight of the magnesium compound; and wherein the renal lithiasis is oxalocalcium renal lithiasis, which is related to the crystallization of calcium oxalate, and wherein the composition synergistically inhibits crystallization of calcium oxalate.

12. The method of claim 11, wherein the composition is in a suitable dosage for administration of between 500 mg/day and 1,000 mg/day.

13. The method of claim 11, wherein the composition further comprises at least one polyphenol.

14. The method of claim 13, wherein the at least one polyphenol is selected from the group consisting of: epicatechin, catechin, gallocatechin, epigallocatechin, quercetin, resveratrol, gallic acid and tannic acid.

15. The method of claim 13, wherein the at least one polyphenol is in the form of plant extract from grape seed.

16. The method of claim 13, wherein the composition comprises between 10% and 30% by weight of polyphenols.

17. The method of claim 11, wherein the composition comprises between 40% and 50% by weight of phytic acid or its salt.

18. The method of claim 11, wherein the composition further comprises lactose, sucrose, talc, cellulose, calcium salts, gelatin or fatty acids.

19. The method of claim 11, wherein the composition is in the form of a pharmaceutical composition, functional food, a nutraceutical product, or a food supplement.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) FIG. 1. It shows the graphical representation of the induction times of the crystallization (in minutes) for a 200 mg/L calcium and 50 mg/L oxalate solution, in synthetic urine, at different magnesium and phytate concentrations.

EXAMPLES

Example 1. Measurement of the Crystallization of Calcium Oxalate in the Presence of Magnesium and Phytate

(2) From a 200 mg/L calcium and 50 mg/L oxalate solution, in synthetic urine, the induction times for the crystallization of calcium oxalate have been calculated in the presence of different phytate and/or magnesium concentrations. Table 1 shows said induction times, which as it can be clearly seen in FIG. 1, increase with the increase in the concentration of magnesium and phytate. Thus, when there is neither magnesium nor phytate, the calcium oxalate takes 1 minute to crystallize. This time increases up to 10 minutes when 100 mg/L magnesium is added and, in turn, it increases up to 44 minutes if, in addition to the 10 mg/L magnesium, 1 mg/L phytate is added.

(3) TABLE-US-00001 TABLE 1 induction times of crystallization (in minutes) for a 200 mg/L calcium and 50 mg/L oxalate solution, in synthetic urine, at different concentrations of magnesium and phytate. mg/L 0 mg/L Mg 25 mg/L Mg 75 mg/L Mg 100 mg/L Mg phytate t (min) t (min) t (min) t (min) 0 1 1.5 6 10 0.5 3 6 12 20 0.75 4 7 18 27 1 6.5 9.5 35 44

Example 2. Effect of the Composition of the Invention on Wistar Rats Subjected to a Lithogenic Diet

(4) A group of Wistar rats was pre-treated with polyphenols extracted from white grape seeds (added to the drinking water in concentrations of 200 mg/L) and phytate (1% of the solid diet fed to the animals, in the form of phytin, which is the calcium magnesium salt). Subsequently, papillary renal lithiasis was induced by administration of ethylene glycol and the preventive treatment was continued. The antilithiatic activity of the polyphenol+phytate mixture was evaluated through the calcium content of the kidneys of the animals (extracted at the end of the experiment) and the corresponding histological studies of the renal tissue, by comparison with the corresponding control groups. It was observed that the applied prophylactic treatment reduced renal calcification by 50%.

Example 3. Effect of the Composition of the Invention on Patients with Problems of Renal Lithiasis

(5) In this example three pharmaceutical compositions of the present invention are illustrated.

(6) Composition 1.

(7) TABLE-US-00002 Compound Amount Calcium-magnesium phytate 300 mg Magnesium citrate 250 mg Epicatechin 100 mg
Composition 2.

(8) TABLE-US-00003 Compound Amount Calcium-magnesium phytate 300 mg Magnesium citrate 250 mg Catechin 150 mg
Composition 3.

(9) TABLE-US-00004 Compound Amount Brown rice extract equivalent to 250 mg an amount of phytate of Magnesium oxide 150 mg Black grape seed extract equivalent to 150 mg an amount of polyphenols of
Composition 4.

(10) TABLE-US-00005 Compound Amount Locust bean germ extract and dry wheat extract 150 mg equivalent to an amount of phytate of Magnesium oxide 100 mg White grape seed extract equivalent to an  90 mg amount of polyphenols of

(11) 200 mg of calcium-magnesium phytate (phytin) together with 200 mg of magnesium citrate and 100 mg of quercetin were orally administered to a patient, twice a day, at breakfast and after dinner. After the treatment, it was observed that the inhibitory capacity of the urine of the patient against the crystallization of calcium oxalate increased 40% with respect to the urine of the own patient before ingesting phytate. The antioxidant capacity of the urine (potentiometrically evaluated using a platinum electrode) increased 15%. These variations may imply from a significant reduction of the recurrence to a total elimination of the calculogenesis process because they eliminate and/or normalize key factors in the calculogenesis process, such as the inhibitory capacity of the urine, oxaluria and the protection against oxidative stress.