The present invention relates to a method of preparing a solution, in particular a dialysis or infusion solution. This invention also concerns a solution, in particular a dialysis or infusion solution, as well as a storage system for preparing such a solution.
Dialysis solutions that have as close to a physiological pH as possible must be prepared for use in hemodialysis as well as in peritoneal dialysis. These solutions having a pH of approximately 7.4, and containing important electrolytes, also contain a physiological buffer system suitable for establishing the desired pH. Since bicarbonate is the physiological buffer found in blood, bicarbonate is generally used as the buffer system for these solutions.
An important disadvantage of a bicarbonate buffer system is that it releases CO2 at a low pH due to outgassing, and is thus unstable. In practice the pH must be kept relatively high to prevent the release of gas. In the presence of appropriate cations, however, the cations can be precipitated with the carbonate at a high pH. This is true, for example, of calcium and magnesium ions usually present in dialysis solutions.
To establish the desired physiological pH of the dialysis solution, a second buffer system is used for buffering, usually containing acetate or other metabolizable acids. To prevent outgassing of a solution containing bicarbonate, while also preventing precipitation of carbonates which occurs especially at high pH, dialysis solutions are usually prepared from two individual solutions stored separately. A first solution containing bicarbonate is stored in one tank, and a second solution, an acidic buffer system, is stored in another tank. The acid component usually also contains the electrolytes needed for dialysis, such as NaCl or KCl.
To prepare a ready-to-use solution, the aforementioned individual solutions are mixed, with the risk of precipitation of carbonate being of only minor importance because the dwell time of the finished dialysis solution in the pipeline system of the dialysis machine is only on the order of approximately one minute.
The solution containing the acid component as well as the solution containing the bicarbonate are usually supplied in the form of concentrate canisters, which are mixed on site and diluted with ultrahigh purity water to the desired concentration. The concentrate is prepared in conventional commercial tanks with a capacity of approximately 10 l. This practice not only leads to considerable difficulties in handling the tanks, but also incurs a considerable expense for storage of the concentrates because different concentrates must be used.
European Patent 526,754 describes the preparation of such a dialysis solution by mixing two individual solutions, where one of the individual solutions is an alkaline reacting bicarbonate solution and the other is a bicarbonate-free acid solution. The acid solution contains metabolizable organic acids, while the essential ingredients of the individual alkaline solution are alkali carbonate and alkali bicarbonate.
To avoid the problem of complicated handling of the concentrate tanks, proposals exist for supplying the substances needed for dialysis in the form of solids, and preparing the required concentrates by dissolving the solids on site. However, with this method it is difficult to use solid acids, which are generally too hygroscopic or unsuitable for adjusting to an optimum pH, especially at a high bicarbonate concentration.
The present invention relates to a solution, in particular an infusion solution or a dialysis solution, that requires only little preparation work and is physiologically tolerable.
In one aspect, the present invention is a method of preparing a dialysis or infusion solution, comprising the steps of dissolving in water in a first container an acid-reacting component that includes at least one of a solid acid and a solid salt, said acid-reacting component being water-soluble and not hygroscopic, and mixing said dissolved acid-reacting component with an alkaline reacting bicarbonate solution in a second container. The method further includes selecting quantity ratios of acid-reacting component and bicarbonate so that an acid-reacting component content does not exceed about 6 mmol per liter of solution, and a bicarbonate content does not exceed about 40 mmol per liter of solution.
In a different aspect, the invention is a dialysis or infusion solution, comprising an alkaline-reacting bicarbonate component and an acid-reacting component comprising at least one of an acid and a salt. The at least one of an acid and a salt are water-soluble and not hygroscopic solids, and the acid and salt content does not exceed about 6 mmol per liter of finished solution, while the alkaline-reacting bicarbonate content does not exceed about 40 mmol per liter of finished solution.
In a third aspect, the invention is a storage system for preparing a dialysis or infusion solution, that includes a first container adapted for containing an acid-reacting component and a second container adapted for containing an alkaline-reacting bicarbonate component. The acid-reacting component is formed of at least one of a solid acid and a solid salt which is water-soluble and not hygroscopic. This has a buffer capacity resulting in a finished solution having an acid and salt concentration of no greater than about 6 mmol per liter of solution and a bicarbonate concentration of up to about 40 mmol per liter of solution.
According to this invention, the method for preparing a solution, in particular a dialysis or infusion solution, includes dissolving in water a component that yields an acid, including a solid acid and/or a solid salt which is water-soluble and not hygroscopic. This step preferably occurs in a first container. The solution can then be mixed with an alkaline reacting bicarbonate solution in a second container, with the quantity ratios being selected so that the acid and/or salt content does not exceed, for example, 6 mmol per liter of finished solution, and the bicarbonate content does not exceed, for example, 40 mmol per liter.
Because of the solid nature of the acid or salt used, preparing such a solution is not problematical. After dissolving the acid or salt in the first container, this solution is mixed with the bicarbonate solution, and despite a relatively high bicarbonate content preferably of up to 40 mmol per liter of finished solution, an acid and/or salt content of less than about 6 mmol per liter of finished solution is sufficient to prepare a physiologically tolerable solution.
In another embodiment of the present invention, the mixture of the solution containing the acid-reacting component and the alkaline reacting bicarbonate solution is diluted with water before being used. Accordingly, a concentrate is first formed from the acid or salt present in the form of a solid in the container, and the concentrate is then diluted with water to the desired value, before or after being mixed with the alkaline reacting bicarbonate solution.
In yet another embodiment of the present invention, the bicarbonate is used in the form of a solid, and the alkaline reacting bicarbonate solution is prepared by dissolving the solid. Such a procedure has the advantage that the use of solids as starting materials simplifies both the preparation and storage of the materials. Thus, according to this invention, the alkaline reacting bicarbonate solution can be prepared in the second container using a solid containing bicarbonate.
It is especially advantageous if the carbonate content per liter of finished solution is in the range between 32 and 35 mmol, to compensate for metabolic acidosis of patients with renal failure.
According to a preferred embodiment of the present invention, the acid and/or salt content per liter of finished solution is xe2x89xa66 meq, and more preferably 2-4 meq. Despite relatively high bicarbonate concentrations of up to 40 mmol/l, an acid and/or salt content of less than 6 meq per liter of finished solution, preferably of 2-4 meq/l, is sufficient to buffer the finished solution to the physiological pH of approximately 7.4.
A further embodiment of the present invention provides for the use of citric acid, isocitric acid, 2-oxoglutaric acid, succinic acid, fumaric acid, malic acid and/or oxalic acid and the salts thereof as respectively the acid and the salt forming the solution. In addition, hydrochlorides of amino acids and the salts thereof may also be used in the same manner.
The present invention also relates to a dialysis or infusion solution having a bicarbonate component that can be used to produce an alkaline reaction, and an acid-reacting component which includes an acid and/or a salt. The acid and the salt are present in the form of solids under normal conditions. For example, the salt and/or acid content preferably does not exceed 6 mmol per liter of finished solution, and the bicarbonate content preferably does not exceed 40 mmol/l.
It is especially advantageous if the bicarbonate content per liter of finished solution is in the range of between 32 and 35 mmol per liter of finished solution. The acid and/or salt content per liter of finished solution may be xe2x89xa66 meq/l, and preferably 2-4 meq/l.
As described above, it is also especially advantageous if the acid or salt used in the solution is citric acid, isocitric acid, 2-oxoglutaric acid, succinic acid, fumaric acid, malic acid and/or oxalic acid and the salts thereof. Likewise, the hydrochlorides of amino acids and the salts thereof may also be used.
The present invention also relates to a system for preparing a solution, in particular a dialysis or infusion solution, that uses at least two storage tanks or containers. An acid-reacting component is stored in one of the containers, and an alkaline-reacting bicarbonate component is stored in the other container. The acid-reacting component includes a solid acid and/or a solid salt which is water-soluble and not hygroscopic. The components have a buffer capacity such that a physiological pH can be established in the finished solution at an acid and/or salt concentration of xe2x89xa66 mmol per liter of finished solution and a bicarbonate concentration of up to 40 mmol per liter of finished solution.
Another embodiment of this invention provides for the alkaline-reacting bicarbonate component in the container to be present in the form of a solid.
According to another preferred embodiment of the present invention, three containers are provided, with the first container holding an acid-reacting component, the second container holding an alkaline-reacting bicarbonate component and the third container holding additives.
It is especially advantageous if all the components and additives in the containers are in the form of solids. The additives may include NaCl.