The present invention relates to a solution for peritoneal dialysis, consisting of at least two single solutions which are combined after a heat sterilization and are administered to a patient, the first single solution containing an osmotic and the second single solution containing a buffer, and one of these single solutions or another single solution containing electrolyte salts. The avoidance of a glucose-like degradation as well as hydrolysis during sterilization and storage while maintaining a neutral mixture pH is achieved according to the invention by the osmotic comprising a glucose polymer and/or glucose polymer derivative, and the pH of the first single solution being between 3.5 and 5.0.The present invention further relates to a twin-chambered pouch consisting of a plastic pouch with at least one first chamber and a second chamber, the first single solution being included in the first chamber and the second single solution being included in the second chamber.

Description of the Invention

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to provide a peritoneal dialysis solution containing glucose polymers and/or glucose polymer derivatives which are not subjected to glucose-like degradation during storage and heat sterilization, and the mixture of which having a pH value in the neutral range.

According to the invention this object is solved by the osmotic comprising a glucose polymer and/or a glucose polymer derivative, and the pH value of the first single solution being in the range of 3.0 to 5.0. It is especially advantageous that the pH is in the range between 4.0 and 4.3, preferably at 4.2. With these pH values essentially no polymer degradation is observed. This is especially true for a pH of 4.0. The addition of 0.2 pH units to the preferred value of 4.2 is intended as a safety measure for the possible generation of acids during sterilisation and storage. In the claimed pH range, no hydrolysis of the osmotic nor a glucose-like degradation takes place in noticable extend. The osmotic can be formed exclusively with the glucose polymer and/or the glucose polymer derivative. It is also conceivable that further osmotically active substances are present.

In a further embodiment of the present invention it is envisioned that the glucose polymer derivative is hydroxyethyl starch (HES). The present invention also refers to other derivatized glucose polymers, in which preferably not the free carbonyl group of the molecules has been modified during derivatization.

DETAILED DESCRIPTION AND PREFERRED EMBODIMENTS

The first single solution may contain the osmotic, calcium ions, magnesium ions, sodium ions, H.sup.+ excess ions and chloride ions.

In a preferred embodiment of the present invention, the buffer contains bicarbonate. This is a very tolerable buffer system being in equilibrium with carbonate in the alkaline range and with CO.sub.2 in the acidic range. Apart from or in addition to bicarbonate, other buffer system are conceivable as well, that buffer in a physiological pH of approx. 7. Hereby, preferably substances are to be named which may be degraded easily to bicarbonate in the body. For example, lactate or pyruvate may be considered. Apart from bicarbonate or other puffer systems, the second single solution further contains mainly sodium ions.

It is advantageous that the bicarbonate concentration is adjusted according to the acidity of the first single solution, and is determined according to the formula: bicarbonate concentration [mmol/L]=5.times.acidity of the first single solution [mmol/L].times.V.sub.A/V.sub.B, with V.sub.A being the volume of the first single solution and V.sub.B being the volume of the second single solution.

At an acidity of 0.2 mmol/L, the optimal bicarbonate concentration is 0.5 to 2.0 mmol/L when the compartments of a twin-chambered pouche are equally sized. Accordingly, the bicarbonate concentration can be in a range the lower limit of which is determined by half of the biocarbonate concentration determined according to claim 6, and the upper limit of which is determined by twice the biocarbonate concentration determined according to claim 6.

In a further embodiment of the present invention it is envisioned that the buffer contains the salt of a weak acid, preferably lactate. The pKa of the weak acid may be <5. It may be envisioned that the buffer contains a mixture e.g. of bicarbonate and the salt of a weak acid, e.g. lactate. If the bicarbonate content is kept low, e.g. .ltoreq.10 mmol/L, as it is suggested in DE 197 48 290 A1, it has the advantage that the CO.sub.2 pressure within the storage pouch is low so that no special provisions have to be made with respect to the pouch foil. A conventional polyolefin foil may be used as a CO.sub.2 barrier.

The first single solution may contain a physiologically tolerable acid, especially hydrochloric acid. With this, the desired pH range of the first single solution can be adjusted without problems.

Apart from the osmotic, the first single solution may contain the following components -- see Original Patent.

In a further embodiment of the present invention it is envisioned that the bicarbonate concentration of the second single solution is in the range between 0.5 and 2.0 mmol/L, preferably 1.0 mmol/L.

It is especially advantageous that the first and second single solutions are storable individually in a twin-chambered pouch. The use of a twin-chambered pouch results in a very convenient handling of the solution, i.e. a reliable separation of the two single solutions during storage, and fast mixing when desired. The separation of the single solutions is reasonable in order to prevent, that unsoluble precipitations are formed using bicarbonate as buffer together with calcium. Furthermore, the reaction of the glucose polymers or their derivatives with lactate as a buffer system can be avoided by the separation.

In addition, the present invention relates to a twin-chambered pouch for a solution according to one of the claims 1 to 12, consisting of a plastic pouch with at least one first chamber and one second chamber, the first single solution being included in the first chamber and the second single solution being included in the second chamber. Favourably, means are envisioned by which the two chambers are separated from each other and the activation of which enables the mixing of the content of both chambers. Hereby, the first and second chamber may be arranged adjacently. Preferably, a weld is provided which separates the chambers and opens in case of pressing onto one of the chambers. If dimensioned accordingly, the weld opens in case of pressing onto one of the fluid-filled chambers so that the contents of both chambers may be mixed and the mixture be finally administered to the patient.

In the following, an example for the preparation of the solution according to the invention is provided:

For preparation of the first single solution, sodium chloride, calcium chloride, magnesium chloride as well as a glucose polymer and hydrochloric acid are dissolved in water under stirring. The amount of the added hydrochloric acid is adjusted so that the pH is in the range between 4.1 to 4.3, preferably 4.2. Whereas a pH of 4.0 is to be regarded as ideal since no polymer degradation is observed, the 0.2 pH units to a ph of 4.2 serve as an addition to account for the possible formation of acids during sterilization and storage.

The acidity of this first single solution may be determined by titration with 0.1 N NaOH to pH 7.0.

For the second single solution, sodium hydrogen carbonate is dissolved in water under slow stirring. The bicarbonate concentration is determined according to the formula: bicarbonate concentration [mmol/L]=5.times.acidity of the first single solution [mmol/L].times.V.sub.AV.sub.B, with V.sub.A being the volume of the first single solution and V.sub.B being the volume of the second single solution.

Deviations from this calculated bicarbonate concentration by 50% down and by 100% up are possible. If the acidity of the first single solution is e.g. 0.2 mmol/L, and if two equally sized compartments of a twin-chambered pouch are used, the optimal bicarbonate concentration is between 0.5 and 2.0 mmol/L.

The single solutions prepared in this way are then filtered through a membrane sterile filter in a cooling tank. After preparation control and release of the solution, they are filled into a multi-layered foil pouch with two chambers, the first single solution being filled into the first chamber and the second single solution being filled into the second chamber. Both chambers are separated from each other by a weld. The compartments are each closed with a connector. Then, the twin-chambered pouch is packed into an outer pouch, and heat-sterilized at 121.degree. C. After heat sterilization, the weld is opened at least in part by pressing onto one of the chambers resulting in a mixing of the solutions, and by which a mixture pH in the range between 6.8 and 7.0, preferably 6.8, is obtained.

 

Claim 1 of 29 Claims

1. A combined solution for peritoneal dialysis, said combined solution comprising at least two single solutions which are heat sterilized prior to combination, the first single solution containing an osmotic and hydrochloric acid in an amount to provide a pH in the range between about 4.0 and 4.3, and the second single solution containing a buffer, and the first single solution or another single solution containing electrolyte salts, wherein the osmotic comprises hydroxyethylene starch and wherein the first single solution and the second single solution are combined prior to use.

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