Dialysis solution

Abstract

The present invention relates to a dialysis solution containing bicarbonate, calcium and phosphate, wherein the dialysis solution contains phosphate having a concentration in the range from up to 0.4 mmol/l, preferably in the range from up to 0.375 mmol/l, or in the range from up to 0.25 mmol/l, and particularly preferably in the range from up to 0.2 mmol/l.

Claims

1. A two-chamber bag comprising first and second chambers holding first and second individual solutions, respectively, which first and second individual solutions are configured to form a ready-to-use dialysis solution upon mixing with one another, wherein the first individual solution contains calcium, magnesium, and chloride, does not contain sodium, and has a pH in the range of 2.4 to 3.0, the second individual solution contains sodium, chloride, bicarbonate, and phosphate, has a volume greater than the first individual solution, and has a pH in the range of 7.0 to 7.8, and the ready-to-use dialysis solution contains the phosphate in a concentration of up to 0.4 mmol/l, the calcium, and the bicarbonate.

2. A bag in accordance with claim 1, characterized in that the dialysis solution contains the phosphate in a concentration range from 0.05 mmol/l to 0.25 mmol/l.

3. A bag in accordance with claim 1, characterized in that the dialysis solution comprises the phosphate in a concentration of 0.05 mmol/l-0.4 mmol/l.

4. A bag accordance with claim 1, characterized in that the dialysis solution further contains electrolytes and at least one osmotic agent or at least one carbohydrate compound.

5. A bag in accordance with claim 1, characterized in that the first individual solution further does not contain at least one of hydrogen carbonate and phosphate.

6. A bag in accordance with claim 1, characterized in that the second individual solution does not contain at least one of calcium, magnesium, potassium, and glucose.

7. A bag in accordance with claim 1 further comprising a separating means which separates the two chambers from one another, wherein the separating means is opened by pressure on one of the chambers.

8. A bag in accordance with claim 1 further comprising a seam which separates the two chambers from one another, wherein the seam is opened by pressure on one of the chambers.

9. A bag in accordance with claim 1, characterized in that the dialysis solution contains the phosphate in a concentration of up to 0.375 mmol/l.

10. A bag in accordance with claim 1, characterized in that the dialysis solution contains the phosphate in a concentration of up to 0.25 mmol/l.

11. A bag in accordance with claim 1, characterized in that the dialysis solution contains the phosphate in a concentration of up to 0.2 mmol/l.

12. A bag in accordance with claim 1, characterized in that the dialysis solution further contains electrolytes and at least one osmotic agent or glucose.

13. A bag in accordance with claim 1, characterized in that the dialysis solution further contains electrolytes and at least one osmotic agent or glucose.

Description

(1) Further details and advantages of the invention will be explained in more detail with reference to an embodiment shown in the drawing.

(2) There are shown:

(3) FIG. 1: pH development of a dialysis solution over time with a pH increase by degasing CO.sub.2;

(4) FIG. 2: pH development of a dialysis solution with and without phosphate over time with a pH increase by degasing CO.sub.2;

(5) FIG. 3: dependence of the duration of the precipitation of calcium carbonate and of the pH of the dialysis solution on the precipitation of calcium carbonate on the phosphate concentration of the dialysis solution; and

(6) FIG. 4: dependence of the duration or the precipitation of calcium carbonate on the phosphate concentration of the dialysis solution without any addition of citrate or phosphate, with the addition of citrate and with the addition of phosphate.

(7) FIG. 1 shows the time development of the pH of a dialysis solution over time during the degasing of CO.sub.2 from the dialysis solution.

(8) The rapid controlled precipitation method of the critical pH method can be used for determining the stability of the dialysis solution, as is described in F. Hui et al: Journal European of Water Quality (Journal Europen d'Hydrologie) T.33 Fasc. 1 (2002).

(9) The results described within the framework of this invention were obtained by a modified rapid controlled precipitation method. The experiment setup comprises 6 3-neck flasks (Carousel-6 from Radleys) which are open toward the top to ensure a uniform degasing of CO.sub.2 from the solution. Furthermore, this setup allows an in-line measurement of e.g. the pH and the conductivity as well as the simultaneous heating of the flasks.

(10) The basic principle of the method used comprises the pH of the mixed solution or of the dialysis solution being slowly raised by controlled degasing of CO.sub.2 until the dialysis solution reaches a metastable state. This can be seen up to the time tg in FIG. 1.

(11) If the dialysis solution collapses due to precipitation of calcium carbonate, this can be detected by a drop in the pH and in the conductivity. Directly after this in time, a white deposition can be visually observed. The maximum pH, which is marked as pH max in FIG. 1, up to which no precipitations occur is considered the characteristic for the stability of a dialysis solution.

(12) As stated, the time tg (time of germination) is the first measurement point at which a drop in the pH is detected.

(13) In FIG. 1, the increase in the pH up to the time tg can be explained by the degasing of CO.sub.2 from the dialysis solution. As can furthermore be seen from FIG. 1, a local pH maximum arises. After this point, oversaturation of the dialysis solution occurs and a precipitation of calcium carbonate takes place. Carbonate ions are removed from the dialysis solution on the precipitation. The pH drops and protons are increasingly formed due to the equilibrium reaction with hydrogen carbonate, which results in the drop in the pH.

(14) The stability of the dialysis solution or of an individual solution can be significantly increased by the addition of phosphate or of orthophosphate, with the collapse of the metastable range being delayed or prevented in full.

(15) This can be seen from FIG. 2. This Figures shows as the line A the pH development of a dialysis solution containing sodium, calcium, magnesium, chloride, hydrogen carbonate and glucose, but without phosphate, over time. Line B shows the pH development of an identical dialysis solution which, as the only difference, contains 0.1 mmol/l phosphate.

(16) The experiment on which FIG. 2 is based was carried out with a filling volume of 275 ml and the 3-neck flasks were closed by diaphragms having openings of 3 mm in diameter to control the degasing of CO.sub.2. The experiment was carried out with a starting pH of 7.4 and at a temperature of 60 C.

(17) As can be seen from the development in accordance with line A, the pH initially increases up to a maximum value of 7.47. The pH then falls due to the precipitation of calcium carbonate. This takes place at a time of 45 min after the start of the experiment, i.e. tg=45 min.

(18) Line B shows that the addition of phosphate has a substantial effect on the pH. The maximum achievable pH amounts to 8.02 and the length of time up to the occurrence of the precipitation of calcium carbonate amounts to around 22 hours. This means that not only the pH at which a calcium carbonate precipitation takes place, but also the time interval until this precipitation occurs is increased by the presence of phosphate.

(19) The effect of phosphate as a means stabilizing the dialysis solution is dependent on the temperature and on the concentration.

(20) FIG. 3 shows the developments of the maximum pH, i.e. of the pH which is measured on the start of the precipitation, as well as the time interval (tg) which elapses from the start of the experiment to the precipitation. The experiments were carried out using the experiment setup described in FIG. 1.

(21) As can be seen from FIG. 3, the stabilizing effects of orthophosphate are dependent on the temperature and on the concentration. The stability of the dialysis solutions significantly depends on the phosphate concentration, which is expressed both in the respectively reached pH max values, i.e. in the maximum pH values, up to which the dialysis solutions are stable, and in the tg values, i.e. in the time intervals which elapse from the experiment start until the precipitation starts and the pH falls again.

(22) In FIG. 3, the lines D, E and F are the developments of the pH max values for a solution temperature of 25 C. (line D), 40 C. (line E) and 60 C. (line F).

(23) A temperature dependence of the stabilization effect furthermore clearly results from FIG. 3. It can thus be easily recognized from FIG. 3 that, for example, at a temperature of 25 C. (columns D), a dialysis solution with a phosphate content of 0.375 mmol/l has the greatest stability; but at a temperature of 40 C. (columns E), a dialysis solution having a phosphate content of 0.2 mmol/l is the most stable. At a temperature of 60 C. (columns F), a dialysis solution having a phosphate concentration of 0.15 mmol/l shows the greatest stability.

(24) FIG. 4 shows the concentration dependence of the stabilizing effect by way of example for a solution temperature of 40 C.

(25) As can be seen from FIG. 4 and in agreement with FIG. 3, a stability maximum is reached at this temperature with a phosphate concentration of 0.2 mmol/l. The dialysis solutions containing phosphate are marked by the letter P. At this temperature, the stability of the dialysis solution drops again with a further increase in the phosphate concentration, which can be recognized by the fact that the time interval tg up to the precipitation again becomes smaller.

(26) The fall in the stability of the dialysis solution at the named temperature of 40 C. from a phosphate concentration of 0.2 mmol/l is due to the fact that calcium phosphates of low solubility are formed.

(27) No calcium phosphate precipitation can be observed in the range G1; in contrast, a calcium phosphate precipitation occurs in the range G2.

(28) It can furthermore be seen from FIG. 4 that an addition of citrate (c=1 mmol/l; no phosphate) (letter C) admittedly effects a certain stabilization of the dialysis solution in comparison with a dialysis solution without stabilization means (letter K), but that the stabilizing effect is much more pronounced in the case of phosphate.

(29) A dialysis solution having 0.1 mmol/l phosphate is thus stable for around twice as long as a dialysis solution having 1 mmol/l citrate under the above named experiment conditions.

(30) It further results from FIG. 4 that a concentration of phosphate in the medically relevant range from 0.8 mmol/l to 1.25 mmol/l (letter H) with an otherwise analog solution composition does not have any increased stability.

(31) In summary, it can thus be stated that the addition of phosphate or of orthophosphate in the claimed concentration ranges results in a significant increase in the stability of bicarbonate-buffered dialysis solutions containing calcium. The probability of precipitation reactions can be substantially reduced, which considerably increases the safety and the durability of dialysis solutions without influencing the medical efficacy.

(32) The small phosphate concentrations in accordance with the invention have no medical efficacy so that the dialysis solutions can be used easily within the framework of the dialysis.