METHOD OF STABILIZING A DIALYSIS SOLUTION

Abstract

The present invention relates to a method of stabilizing a dialysis solution that includes calcium ions and bicarbonate ions, wherein a phosphate and/or an organic phosphate ester is added to the dialysis solution at a distance of time from its preparation.

Claims

1. A method of stabilizing a dialysis solution that includes calcium ions and bicarbonate ions, characterized in that a phosphate and/or an organic phosphate ester is added to the dialysis solution at a distance of time from its preparation.

2. A method in accordance with claim 1, characterized in that the phosphate is an orthophosphate; and/or in that the organic phosphate ester is an organic ester of the orthophosphate.

3. A method in accordance with claim 2, characterized in that the organic ester of the orthophosphate is a glycerol orthophosphate.

4. A method in accordance with claim 1, characterized in that the phosphate is added in an amount of up to 0.4 mmol/l.

5. A method in accordance with claim 1, characterized in that the phosphate is added in an amount of at least 0.05 mmol/l.

6. A method in accordance with claim 1, characterized in that the organic phosphate ester is added in an amount of up to 1.25 mmol/l.

7. A method in accordance with claim 1, characterized in that the organic phosphate ester is added in an amount of at least 0.8 mmol/l.

8. A method in accordance with claim 1, characterized in that both a phosphate and an organic phosphate ester are added to the solution at a distance of time from its preparation, with provision preferably being made that the concentration ratio between the phosphate and the organic phosphate ester is between 0.3/0.7 and 0.9/0.1.

9. A method in accordance with claim 1, characterized in that the distance of time from the preparation amounts to more than 30 minutes, more than 60 minutes, more than 90 minutes, or more than 105 minutes.

10. A method in accordance with claim 1, characterized in that the distance of time from the preparation amounts to more than one week, more than one month, more than six months, or more than one year.

11. A method in accordance with claim 1, characterized in that the pH of the solution at the time of the subsequent addition is greater than 7.2, greater than 7.4, or greater than 7.6

Description

[0021] Further details and advantages of the invention result from the experiments and embodiments described in the following with reference to the Figures. There are shown in the Figures:

[0022] FIG. 1: an exemplary development of the pH of a dialysis solution over its life;

[0023] FIG. 2: a schematic representation of chemical processes during the preparation and during the life cycle of a dialysis solution;

[0024] FIG. 3: Values for pHmax and tG in the experiment of Example 1;

[0025] FIG. 4: Phototrode signal for selected data points in the experiment of Example 1:

[0026] FIG. 5: Values for pHmax and tG in the experiment of Example 2; and

[0027] FIG. 6: Phototrode signal for selected data points in the experiment of Example 2.

[0028] The pH of the solution is increased by the CO.sub.2 degassing from a bicarbonate-buffered dialysis solution, which promotes the precipitation of calcium carbonate in the case of solutions containing calcium. The pH at which a significant precipitation of calcium carbonate starts is a criterion for the stability of the solution and is subsequently called pHmax. The higher the value for pHmax, the more stable the solution. The time at which the significant precipitation of calcium carbonate starts is subsequently called tG to represent the “time of germination”. An exemplary development of the pH of a dialysis solution over its life is shown in FIG. 1, with pHmax in this illustration being assumed as 8.0 and with tG not yet having been reached in the time period shown.

[0029] The stabilizing effect of a subsequent addition of phosphate or of a phosphate ester to existing dialysis solutions was examined using the rapid degassing method in a carousel setup. THz rapid degassing method in this variant allows an accelerated aging of dialysis solutions by degassing the CO.sub.2 from the bicarbonate buffer. The degassing of CO.sub.2 that normally occur slowly during the life of the products can be simulated within a few hours with this experiment setup.

[0030] The chemical processes in the preparation and in the degassing of the solution are shown schematically in FIG. 2. CO.sub.2 is thus introduced into the solution in the preparation to reduce the pH in the solution. This process gradually reverses during the life cycle due to degassing processes, whereby, with a resulting higher pH, an unwanted precipitation of calcium carbonate begins from a certain point onward.

EXAMPLE 1

[0031] The dialysis solution DUOSOL 4551 of B. Braun is exposed to a simulated aging at 40° C. in a plurality of experiments with and without the addition of orthophosphate as part of the above-described rapid degassing method. The dialysis solution DUOSOL 4551 containing calcium does not contain any phosphates as stabilization agents and is therefore susceptible to precipitation reactions.

[0032] After a specific time period, 250 μl of a parent solution having 100 mmol/l orthophosphate is added to a plurality of flasks containing 250 ml DUOSOL 4551, which results in a concentration of 0.1 mmol/l of orthophosphate in the flask. Three separate experiments are carried out for each data point and the mean value is used. The results with respect to pHmax and tG are shown in FIG. 3. The phototrode signal for selected data points is shown in FIG. 4.

[0033] Without any addition of orthophosphate, a precipitation of calcium carbonate begins after approximately two hours, which can be recognized from the decrease of the transmission of FIG. 4. The addition of orthophosphate after the start of the precipitation has an inhibiting effect. A dissolution of this precipitate is not observed. An addition after the start of precipitation therefore slows down the further precipitation process.

[0034] It can be seen from FIG. 3 that there is no interaction between the stabilizing effect and the time of the addition of orthophosphate. The large standard deviation that can be recognized in FIG. 3 for the measurement point at 105 minutes results from the fact that a significant precipitation had already started on two of the three repetitions of the experiment.

Example 2

[0035] The experiment of Example 1 is repeated in the same manner with the only difference that glycerophosphate is added instead of orthophosphate this time. That is, after a specific time period, 2.5 ml of a parent solution having 100 mmol/l glycerophosphate is added to the flasks containing 250 ml DUOSOL 4551, which results in a concentration of 1.0 mmol/l of glycerophosphate in the flask. The results with respect to pHmax and tG are shown in FIG. 5. The phototrode signal for selected data points is shown in FIG. 6. Similar conclusions can be drawn from these graphs as were made for Example 1 with reference to the graphs of FIGS. 3 and 4.

[0036] In summary, it can be stated that the time-delayed addition of phosphates or of phosphate esters to bicarbonate buffered dialysis solutions containing calcium has the same stabilizing effect with respect to a precipitation of calcium carbonate as an initial addition during the preparation of the solution. Even aged solutions having an elevated pH can be stabilized and thus made safer by this procedure. This principle works before and also during a dialysis treatment.

[0037] In the case of organic phosphate esters and in particular of glycerophosphate, the addition of around 1 mmol/l enables the setting of a physiological phosphate concentration with a simultaneous increase in stability with respect to precipitation reactions of calcium carbonates.