Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Aluminum – calcium or magnesium element – or compound containing
Reexamination Certificate
2000-03-22
2004-02-10
Page, Thurman K. (Department: 1616)
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Aluminum, calcium or magnesium element, or compound containing
C424S666000, C424S677000, C424S678000, C424S679000, C424S680000, C424S681000, C424S686000, C424S717000, C514S023000, C514S557000, C514S574000, C514S722000, C604S082000, C604S408000, C604S410000
Reexamination Certificate
active
06689393
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a solution, in particular for hemodialysis or peritoneal dialysis and a method for preparing same.
BACKGROUND OF THE INVENTION
The most important functional components of hemodialysis or peritoneal dialysis solutions are electrolytes which preferably include calcium ions, sodium ions, magnesium ions and chloride ions, a buffer system, and a suitable osmotic medium.
A bicarbonate buffer having the advantage of good physiological tolerability is generally used as the buffer system, but depending on the pH of the solution, it is partially in carbonate form in an alkaline medium and in equilibrium with CO2 in an acidic range. In addition to bicarbonate, other buffers can also be used, providing they have sufficient buffering effect in the physiological pH range of approximately 7. Suitable buffers include lactate and pyruvate, which can be degraded easily to bicarbonate in the body.
The osmotic medium is usually glucose, which is tolerated well in the desired osmolarity range.
One important problem in preparing a dialysis solution containing the functional components is that bicarbonate and calcium must usually be stored separately to prevent formation of an insoluble calcium carbonate precipitate. Although such a precipitate can be prevented in an acidic range, there is the problem of the bicarbonate-CO
2
equilibrium being on the CO
2
side in the acidic range. The relatively high resulting CO
2
partial pressure requires a bag film with a large, i.e., effective, CO
2
barrier.
If glucose is used as the osmotic medium, glucose may react with the other components of the solution during heat sterilization of the solution, and degradation products which might have a harmful effect on the body may be formed. In particular the reaction of glucose with lactate, which is also used as a buffer, bears mentioning.
Therefore, it is known from International Patent WO 93/09820, for example, that glucose and the other components of the dialysis solution may be sent for heat sterilization separately. Said patent discloses a dual-chamber vessel where all the important components of the dialysis solution except for glucose are accommodated in a large compartment, while the glucose or glucose-like components are stored in a second compartment. This makes it possible to effectively prevent the formation of glucose degradation products during heat sterilization. After heat sterilization, the components of the two compartments are mixed and the solution is used for hemodialysis or peritoneal dialysis in a known manner.
European Patent 613 688 A1 describes a dialysis fluid consisting of multiple individual concentrates. A uniform, standardized basic concentrate and an individually selected additive concentrate are provided. The basic concentrate contains sodium chloride and sodium bicarbonate. The additive concentrate preferably contains the other electrolytes and glucose. In addition to the separation of glucose from the buffer system and the associated reduction in formation of unwanted degradation products, this yields the advantage that the composition of the dialysis solution can be adapted to the prevailing needs of the patients through the individually selected additive concentrate. This makes it possible to administer potassium salts, calcium salts and magnesium salts as well as glucose in individually adjusted doses.
European Patent 402 505 A1 discloses a method and a device for continuous cyclic peritoneal dialysis, where a glucose pump is connected to an inlet line for a dialysis solution leading to the patient. Depending on the delivery head of the glucose pump, the glucose concentration in the peritoneal dialysis solution supplied to the patient may be adjusted. The glucose content in the solution to be administered is adjusted on the basis of the quantity of ultrafiltrate taken from the patient.
The previously known methods of preparing dialysis solutions have the disadvantage that although different concentrations or profiles of components, in particular glucose, can be achieved in the finished mixture by combining two individual solutions, mixing the individual solutions always leads to a corresponding change in the concentrations of the other components as well. For example, if glucose is added in the method known from European Patent 402,505 A1, this also results in changes in the concentrations of the other components of the dialysis solution, e.g., the electrolytes or the pH, depending on the mixing ratio.
OBJECTS OF THE INVENTION
Therefore, the object of the present invention is to provide a solution, in particular for hemodialysis or peritoneal dialysis, and a method of preparing same, by means of which the glucose concentration can be varied as desired without influencing the concentration of the other components.
This object is achieved by a solution consisting of at least three individual solutions which are combined and administered after heat sterilization, where the first individual solution contains calcium ions, electrolyte salts and optionally glucose in concentrations of 0-1000 mM and is acidified to a pH below 4.0 with a physiologically tolerable and effective acid, where the second individual solution contains glucose in a different concentration and all the other components of the first individual solution in the same concentration, i.e., as in the first individual solution, and where the third individual solution contains a buffer in the physiological range.
Such a solution yields the advantage that the glucose concentration can be varied as desired according to the mixing ratio of the first and second individual solutions without affecting the concentrations of the other components.
Furthermore, the solution according to the present invention has the advantage that the calcium ions and the bicarbonate are accommodated in separate compartments, thus avoiding the disadvantages of simultaneous presence of both components as described above.
Sterilization of the individual solutions according to the present invention is not problematical, as it has been found that glucose can be sterilized without significant problem at a pH of less than 4.0. Fewer degradation products of glucose are formed due to the low pH. In this way, it is possible to prevent or greatly reduce infusion pain in dialysis patients due to the low concentration of degradation products, i.e., the dialysis solution prepared from the individual solutions according to the present invention has a high biocompatibility. The buffer used in the third individual solution has a pH of approximately 7.2 to 7.4. The buffer solution may consist of a bicarbonate solution, for example, with the bicarbonate content in the mixed solution being below 40 mM. The buffer is preferably prepared from HCO
3
−
and a salt of a weak acid.
It is especially advantageous if the third individual solution contains bicarbonate in a maximum concentration of 10 mmol/L. This makes it possible to minimize the CO
2
pressure inside the respective compartment so that no special CO
2
barrier need be provided to prevent the escape of CO
2
. Instead, use of a normal polyolefin film or a normal PVC film is sufficient to keep the bicarbonate concentration constant. The buffer of the third individual solution can contain solely bicarbonate. It is likewise possible for the buffer to also contain a salt of a weak acid, preferably lactate, whose buffer capacity is supported by the bicarbonate in the combined buffer.
In another embodiment of the present invention, the second individual solution may not contain any glucose. In this case, the glucose is provided only in the first individual solution and is metered by mixing this solution with the second individual solution in the desired concentration. It is of course also possible for the second individual solution to also contain glucose, but in a different concentration than the first individual solution.
It is especially advantageous if the first and second individual solutions have a pH of 2.8 to 4.0, preferably a pH of 3.7, and if t
Choi Frank
Fresenius Medical Care Deutschland
Kenyon & Kenyon
Page Thurman K.
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