Title:  Solution for peritoneal dialysis

United States Patent:  6,277,815

Assignee:  Fresenius Medical Care Deutschland GmbH (DE)

Filed:  October 30, 1998

Foreign Application Priority Data:   Oct 31, 1997[DE] (197 48 290)

A solution for peritoneal dialysis or for infusion comprises two single solutions which, after heat sterilization, are brought together and dispensed, with the first single solution containing calcium ions, additional electrolytic salts and glucose in an osmotically effective concentration and the second single solution containing bicarbonate and a weak acid with pKa<5. To provide a biocompatible solution, in particular for use as a peritoneal dialysis solution, the first single solution is acidified with a physiologically compatible acid to a pH of below 3.2. The second single solution contains bicarbonate only in a proportion which does not exceed 10 mmol/l.

SUMMARY OF THE INVENTION

An object of the present invention is to provide a solution for peritoneal dialysis or infusion which, on the one hand, ensures good storability and easy and safe handling and, on the other hand, good biocompatibility.

The present invention provides a solution for peritoneal dialysis or infusion comprising two single solutions which, after heat sterilization, can be brought together and dispensed. The first single solution contains calcium ions, additional electrolytic salts and glucose in an osmotically effective concentration and the second single solution contains bicarbonate and the salt of a weak acid with pKa<5. The present invention is characterized in that the first single solution is acidified with a physiologically compatible acid to a pH of below 3.2 and the second single solution has a bicarbonate content which does not exceed 10 mmol/l.

Here, a buffer from lactate and bicarbonate is provided in accordance with the present invention. Due to the bicarbonate proportion, a physiological pH of around 7.2 to 7.4 can be achieved in the final solution. It is essential that the bicarbonate content is below 10 mmol/l, since, surprisingly, as a result the CO₂ pressure inside the storage bag is so low that the barrier of a normal polyolefin film or of a normal PVC film is sufficient to keep the bicarbonate concentration constant. The difficult handling problems of the solution. which usually contains bicarbonate, and/or the requirements of a CO₂ barrier film can thus be avoided. To keep the bicarbonate content that low the main buffer comprises a salt of a physiologically weak acid, preferably lactate, whose buffer capacity is merely supported by the bicarbonate in this combined buffer. While lactate and bicarbonate can be stored in a bag chamber, glucose and the electrolytes--and together with the electrolytes the calcium ion--can be acidified and sterilized in a second chamber to a pH of below 3.2. After sterilization the contents of both chambers can be combined, mixed and dispensed to the patient.

The solution in accordance with the present invention has a compatible pH and fewer glucose breakdown products. Thus, it achieves high biocompatibility. It is particularly advantageous that, with the solution in accordance with the present invention, the pain of administration can also be avoided for dialysis patients due to a reduction of the glucose breakdown.

In accordance with a particularly advantageous embodiment the first single solution, which comprises calcium ions, additional electrolytic salts and the glucose, has a pH of 2.8 to 3.2, preferably a pH of 3. Due to the acidification of this single solution which contains the glucose, a clear reduction of the glucose breakdown is achieved during sterilization. The second single solution, which contains bicarbonate and the salt of a weak acid, should have a pH of 8 to 8.5. When mixing, the single solutions at a ratio of about 1 to 1 (by weight), a pH of 7.2 to 7.4 is achieved for the final solution.

In addition to calcium ions and glucose, the first single solution may also contain sodium ions, magnesium ions, H⁺ excess ions and chloride ions as additional electrolytes. The second single solution may contain hydrogen carbonate ions in addition to sodium ions and lactate ions, for example pyruvate ions, .alpha.-keto glutarate ions etc.

The physiologically compatible acid of hydrochloric acid for acidification to a pH of below 3.2 is also advantageous.

A particularly compatible separation of the solution into the two single solutions is achieved as follows:

First Single Solution:
    Sodium [mmol/l]        180 to 200, preferable 193
    Calcium [mmol/l]       2 to 4, preferably 2.5 to 3.5
    Magnesium [mmol/l]     0.8 to 1.2, preferably 1.0
    H + excess ions [mmol/l] 0.9 to 1.1, preferably 1.0
    Chloride [mmol/l]      197 to 210, preferably 203
    Glucose [mmol/l]       100 to 500, preferably 166.5, 252 or 473

Second Single Solution:
          Sodium [mmol/l]              70 to 80, preferably 75
          Lactate [mmol/l]             65 to 75, preferably 70
          Hydrogen carbonate [mmol/l]  4 to 6, preferably 5.0.

Claim 1 of 13 Claims

What is claimed is:

1. A solution for peritoneal dialysis or infusion comprising:

a first single solution comprising calcium ions, additional electrolytic salts and glucose in an osmotically effective concentration, the first single solution being acidified with a physiologically compatible acid to a pH of below 3.2; and

a second single solution comprising bicarbonate and the salt of a weak acid with a pKa<5, the bicarbonate of the second single solution not exceeding a concentration of 10 mmol/l;

wherein the first and second single solutions are brought together after heat sterilization to form a dispensable finished solution.

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