BACTERIOSTATIC HEMODIALYSIS CONCENTRATE

Abstract: Hemodialysis bicarbonate and acid concentrates which are bacteriostatic and bactericidal. Sodium bicarbonate concentrate is made biocidal by including greater than 28 grams per liter of sodium chloride. The excess sodium chloride in the bicarbonate concentrate is obtained from a decrease in the sodium chloride concentration in the acid concentrate. Powdered mixtures having the proper ratios of sodium chloride to bicarbonate may be dissolved in purified water used in hemodialysis to obtain the biocidal hemodialysis concentrates.

Description: BACTERIOSTATIC HEMODIALYSIS CONCENTRATE - - DESCRIPTION Field of the Invention This invention is directed to hemodialysis solu- tions and more particularly to dialysis concentrate. Background of the Invention Dialysis fluids for hemodialysis must contain either acetate, bicarbonate or other similar buffers to maintain the pH of the solution within acceptable limits. Most hemodialysis solutions contain either sodium acetate or sodium bicarbonate buffer. Bicarbonate hemodialysis is preferred over ace¬ tate hemodialysis. Less dialysis induced morbidity and vascular instability has been reported when bicarbonate is used instead of acetate; When acetate is metabolized by the body undesirable triglyceride levels may be formed. Most dialyzing solutions are prepared by use of commercial liquid concentrate. When appropriately diluted, the desired electrolyte concentration is obtained. Sodium acetate has been traditionally used rather than bicarbonate to maintain stability in storage. Acetate concentrate was usually considered to be • bactericidal. The major reason bicarbonates are less desirable than acetate is the lack of ionic stability and the growth of microorganisms within the bicarbonate concentrate. Traditionally, sodium bicarbonate concentrate includes sodium chloride. However, the level of sodium chloride in the concentrate has always been less than about 23.8 grams per liter. Such solutions are not adequately bactericidal or bacteriostatic. Summary of the Invention The present invention provides compositions which, when properly diluted, yield bicarbonate hemodiaysis solu- tion. The inventive compositions provide acid hemodialysis concentrate and bicarbonate concentrate which are bac¬ teriostatic and bactericidal in the same manner as acetate concentrate. Hemodialysis solution is typically prepared by mixing together and diluting an acid concentrate and a bicarbonate concentrate. The typical acid concentrate includes sodium chloride, calcium chloride, potassium chloride, magnesium chloride, acetic acid and dextrose. The sodium chloride level in the acid concentrate was typi- cally at a concentration which resulted in a pH of between 0.8 and 3.0 which is bacteriostatic. As stated above, bicarbonate concentrate was prepared with sodium bicar¬ bonate and sodium chloride concentration below 23.8 grams per liter. Such prior art bicarbonate concentrates are not bacteriostatic or bactericidal. The inventor has discovered that a bactericidal and bacteriostatic bicarbonate concentrate is formed when¬ ever the sodium chloride concentration exceeds approximate¬ ly about 28 grams per liter. In order to add additional sodium chloride to a bicarbonate concentrate, the inventor reduced the quantity of sodium chloride in the acid con¬ centrate such that the total amount of sodium chloride pre¬ sent in the final hemodialysis solution would be unchanged. Surprisingly, the inventor found that when the bicarbonate concentrate is made bactericidal by increasing the sodium chloride concentration, the corresponding decrease of sodium chloride in the acid concentrate did not make the acid concentrate non-bacteriostatic. It was found that the pH of acid concentrate having a lower sodium chloride con- tent was between 0.8 and 3.0 which provides bacteriostatic properties. Bacteriostatic and bactericidal qualities of the acid concentrate and bicarbonate concentrate solutions are achieved with the use of materials which are already in routine application in dialysis therapy. Long term studies to show compatibility for human use is not required since the final hemodialysis solution will have the same parame¬ ters as was previously provided by the prior art mixtures. The distinct advantages in using bicarbonate may be achieved without the undesirable microorganism growth which had previously been encountered with the use of bicarbonate concentrate. Hemodialysis solutions may be formulated on site with the use of three stream artificial kidney machines such as the AK-10 system as sold by Gambro, Inc. The ad¬ vantages of the invention may be realized by shipping powdered chemical compositions which are pre-measured such that the addition of a specified quantity of water will result in the bateriostatic and bactericidal concentrates. The powdered chemcials m,ay be diluted with water through the use of a Renapak™ processing machine as sold by Renal Systems, Inc of Minneapolis, Minnesota. Alternatively, the acid concentrate may be prediluted with water to its bac¬ teriostatic concentration. Either the powdered bicarbonate concentrate composition or the diluted bicarbonate con¬ centrate composition may then be utilized. In any of the forms which the hemodialysis solution user receives the composition, the compositions will be bactericidal and bac¬ teriostatic. Powdered formulations are of course bac- teriostatic to begin with and when properly diluted provide the bacteriostatic concentrate properties of the invention. Detailed Description of the Invention Bicarbonate containing hemodialysis solution usually includes sodium chloride, calcium chloride, potassium chloride, magnesium chloride, acetic acid, sodium bicarbonate and, optionally, dextrose. The exact quantity of each ion within a hemodialysis solution may vary depending on the needs of a particular patient. However, typical hemodialysis solution has about 140 milliequivalents per liter of sodium, 3.5 milliequivalants per liter of calcium, 1 milliequivalent per liter of magne¬ sium, 1 milliequivalants per liter of potassium, 106.5 milliequivalents per liter of chloride, 35 milliequivalents per liter of bicarbonate and 4 milliequivalents per liter of sodium acetate. The concentration of each may be vary up or down in custom prepared solutions. Most manufac¬ turers supply a series of hemodialysis solutions which have varying concentrations of the chemical species there- within. The advantages of the invention may be achieved such that any of the commercially available, standard hemo¬ dialysis solutions or custom hemodialysis solutions may be produce . The invention involves providing sufficient sodium chloride in a bicarbonate concentrate such that the concentration of sodium chloride in the bicar¬ bonate concentration is at least 28 grams per liter. The higher the concentration of sodium chloride in the bicar- bonate concentrate, the lower the sodium chloride con¬ centration is in the acid concentrate. The total amount of sodium chloride in hemodialysis solution prepared from the bactericidal and bacteriostatic bicarbonate and acid con¬ centrates remains unchanged. As the quantity of sodium chloride within the bicarbonate concentrate increases it decreases in the acid concentrate, such that the total amount of sodium chloride in the final hemodialysis solu¬ tion is unchanged. It has been found that a bicarbonate concentrate of 28.0 grams NaCl per liter will be bacteriostatic. How¬ ever, since such a solution is at the lower limit which will create a bacteriostatic solution, the concentrate should be aged for seven days and tested for growth before use. The concentrate is bacteriostatic after aging for about one week. There is a possibility of bacterial growth before the seven days have elapsed at the marginally bacterio¬ static concentration. Preferably, the concentration of NaCl is grams per liter in the bicarbonate concentrate is about 35.3 or higher. The higher concentrations of salt have even greater bacteriostatic properties. The concentration of NaCl is limited by its solubility characteristics when in solution with sodium bicarbonate. At temperature ranges in which the concentrate will probably be used in forming dialysis solution the maximum concentration of NaCl would be about 200 grams/liter. The normal concentration of bicarbonate in a human body is about 20 milliequivalents (meq.) per liter. Hemodialysis usually involves a solution having about 39 meq. bicarbonate per liter. However, in some applications, the dialysis may involve 20 to as low as 15 meq. bicar¬ bonate per liter. The maximum sodium bicarbonate in the bicarbonate concentrate would be about 164 grams/liter if the concentrate is prepared at an elevated temperature. The concentration of sodium chloride in the acid concentrate depends on the concentration of sodium chloride in the bicarbonate concentrate. The maximum sodium chloride concentration in the acid concentrate is limited by the necessity of maintaining at least 28 grams per liter of sodium chloride in the bicarbonate concentrate. The concentration of sodium chloride in the acid concentrate may be zero, with all of the sodium chloride being present in the bicarbonate concentrate. Example 1 (A) Acid Concentrate Grams per Liter Sodium Chloride 118.4 Calcium Chloride 9.5 Potassium Chloride 5.5 Magnesium Chloride 3.7 Acetic Acid 8.8 Dextrose 73.7 (B) Bicarbonate Concentrate Grams per Liter Sodium Chloride 52.9 Sodium Bicarbonate 66.0 In order to make up 36.83 liters of prepared hemodialysis solution, acid concentrate and bicarbonate concentrate were prepared to the above concentrations. The bicarbonate concentrate consisted of 96.8 grams NaCl and 120.6 grams of sodium bicarbonate diluted to 1.83 liters with water. The acid concentrate was prepared by adding 118.4 grams NaCl, 9.5 grams calcium chloride, 5.5 grams potassium chloride, 3.7 grams magnesium chloride, 8.8 grams acetic acid and 73.7 grams dextrose to water to a total of 1.0 liter. Both the acid concentrate and bicarbonate con¬ centrate prepared as detailed above are bacteriostatic. Dialysis solution is prepared by adding 34.83 liters of water, 1.83 liters of bicarbonate concentrate and 1.0 liters of acid concentrate together. The bicarbonate and/or acid concentrates may be prepared from the raw powder constitutes singly or more preferably from prepackaged containers which, when diluted as indicated on the label, will yield the bacteriostatic concentrates of the invention. In considering this invention it should be remembered that the present disclosure is illustrative- only, and that the scope of the invention is determined by the appended claims.

Claims: AMENDED CLAIMS [received by the International Bureau on 18 March 1986 (18.03.86); original claims 1, 3, and 4 cancelled; claims 2 and 9 amended; new claim 12 added (3 pages)] 1. (Cancelled) 2. (Amended) In a composition for use in preparing animal dialysis solution from an acid concentrate and a bicarbonate concentrate, said bicarbonate concentrate com¬ prising: a) sodium bicarbonate; b) sodium chloride; and c) water, the improvement comprising: a sodium chloride concentration being at least 28 grams per liter of water and no greater than 200 grams per liter thereby making the concentration bacteriostatic. 3. (Cancelled) 4. (Cancelled) 5. A composition for use in preparing dialysis bicarbonate concentrate, wherein the desired concentration 9. Combinable aqueous bacteriostatic concentrates for forming upon dilution dialysis solution for using in human dialysis comprising: a) an acid concentrate including calcium chloride, potassium chloride, mafnesium chloride; acetic acid, dextrose and sodium chloride; b) bicarbonate concentrate including sodium bicarbonate and sodium chloride, said sodium chloride being at a concentration of at least 28 grams per liter, the maximum sodium chloride concentration being about 200 grams per liter. 10. A bacteriostatic bicarbonate concentrate for use in preparing dialysis solution for use in dialyzing ani¬ mals, said dialysis solution having between about 80 to about 120 milliequivalents each of sodium and chloride derived from sodium bicarbonate, said bicarbonate concen¬ trate comprising: a) all of the sodium bicarbonate required to yield 15-45 milliequivalents of bicarbonate in the dialysis solution; and b) sodium chloride in an amount equal to or greater than 28 grams per liter up to all of the sodium and chloride derived from sodium chloride in the dialysis solution. 11. A composition for use in preparing a bacterio¬ static bicarbonate concentrate for use in preparing hemo¬ dialysis solution, said composition comprising: a) sodium chloride; b) sodium bicarbonate; c) said sodium chloride being in a quantity such that upon dilution with water to yield a sodium bicar¬ bonate concentration of between about 50 and 164 grams per liter, said sodium chloride concentration will be at least 28 grams per liter and less than about 200 grams per liter. •i 12. In a bicarbonate dialysis concentrate comprising water, sodium chloride and sodium bicarbonate, the improve¬ ment comprising: a sodium chloride concentration greater than 28 grams per liter and less than the solubility limit of sodium chloride in water, said concentrate thereby being bacteriostatic.

Inventors: COSENTINO LOUIS C, HNOJEWYJ ANATOL M, JANSEN WALTER B, COSENTINO, LOUIS, C., HNOJEWYJ, ANATOL, M., JANSEN, WALTER, B.
Applicants: RENAL SYSTEMS, RENAL SYSTEMS, INC.
Application year: 1985
Main classification: A61K33
IPC codes: A61K33, A61M1