Dialysis precursor composition

Abstract

The present invention concerns a dialysis acid precursor composition for use during preparation of a dialysis acid concentrate solution and for mixing with water, a sodium containing concentrate, and a bicarbonate containing concentrate into a ready-for-use dialysis solution. Said dialysis acid precursor composition consists of powder components comprising glucose, at least one dry acid and at least one calcium salt, and optionally potassium salt, and magnesium salt. According to the invention said glucose and said at least one calcium salt, are present as anhydrous components in said dialysis acid precursor composition.

Claims

1. A dialysis acid precursor composition for use during preparation of a dialysis acid concentrate solution and for mixing with water, a sodium containing concentrate, and a bicarbonate containing concentrate into a ready-for-use dialysis solution, the dialysis acid precursor composition consisting of: powder components comprising a glucose powder, at least one dry acid powder, a calcium chloride powder, and a hydrated magnesium chloride powder selected from the group consisting of a magnesium chloride hexahydrate powder and a magnesium chloride dihydrate powder, wherein the glucose powder and the calcium chloride powder are present as anhydrous components in the dialysis acid precursor composition, wherein the calcium chloride is in a quantity such that a concentration of 30-500 mM calcium ions is provided in the dialysis acid concentrate solution, and wherein the dialysis acid precursor composition is sealed in a moisture-resistant container with a water vapour transmission rate less than 0.3 g/m2/d at 38° C./90% RH.

2. A dialysis precursor composition according to claim 1, wherein said at least one dry acid is selected from the group comprising lactic acid, citric acid, gluconic acid, glucono-δ-lactone, N-acetyl cystein and α-lipoic acid.

3. A dialysis precursor composition according to claim 1, wherein said moisture-resistant container has a water vapour transmission rate of less than 0.2 g/m2/d at 38° C./90% RH.

4. A dialysis precursor composition according to claim 1, wherein said moisture-resistant container has a water vapour transmission rate of more than 0.05 g/m2/d at 38° C./90% RH.

5. A dialysis precursor composition according to claim 1, wherein said dialysis precursor composition is configured to be mixed with a prescribed volume of water within said moisture-resistant container to provide a dialysis acid concentrate solution.

6. The dialysis acid precursor composition of claim 1 wherein the powder components further comprise a potassium salt.

7. The dialysis precursor acid composition according to claim 1, wherein the powder components consist of the glucose powder, the at least one dry acid powder, the calcium chloride powder, the hydrated magnesium chloride powder, and a potassium salt, wherein the glucose powder and the calcium chloride powder are present as anhydrous components.

8. A method of providing a dialysis acid concentrate solution for dilution with water, a sodium containing concentrate, and a bicarbonate containing concentrate to produce a ready-for-use dialysis solution, the method comprising: (a) providing a dialysis precursor composition comprising a glucose powder, at least one dry acid powder, a calcium chloride powder, and a hydrated magnesium chloride powder selected from the group consisting of a magnesium chloride hexahydrate powder and a magnesium chloride dihydrate powder, wherein the glucose powder and the calcium chloride powder are present as anhydrous components in the dialysis acid precursor composition, (b) providing the dialysis precursor composition in a sealed, moisture-resistant container with a water vapour transmission rate less than 0.3 g/m2/d at 38° C./90% RH, and (c) adding a prescribed volume of water to the dialysis precursor composition in the container and mixing thereof, thereby providing the dialysis acid concentrate solution, wherein the calcium chloride is in a quantity such that a concentration of 30-500 mM calcium ions is provided in the dialysis acid concentrate solution.

9. The method of claim 8 further comprising using the dialysis acid precursor composition to prepare at least one of a dialysis solution, an infusion solution, a replacement solution, a rinsing solution and a priming solution.

10. The method of claim 8 wherein the dialysis precursor composition includes a potassium salt.

11. The method of claim 8, wherein the dialysis precursor composition consist of the glucose powder, the at least one dry acid powder, the calcium chloride powder, the hydrated magnesium chloride powder, and a potassium salt, wherein the glucose powder and the calcium chloride powder are present as anhydrous components.

12. A method using a dialysis acid concentrate solution, the method comprising: providing a dialysis precursor composition comprising an anhydrous glucose powder, a dry acid powder, an anhydrous calcium chloride powder, and a hydrated magnesium chloride powder selected from the group consisting of a magnesium chloride hexahydrate powder and a magnesium chloride dihydrate powder; sealing the dialysis precursor in a moisture-resistant container having a water vapor transmission rate less than 0.3 g/m2/d at 38° C./90% RH; and adding a prescribed amount of water to the dialysis precursor composition in the container to form a dialysis acid concentrate solution, wherein the calcium chloride is in a quantity such that a concentration of 30-500 mM calcium ions is provided in the dialysis acid concentrate solution.

13. The method of claim 12 comprising diluting the dialysis acid concentrate solution with at least one of a sodium containing concentrate and a bicarbonate containing concentrate to produce a ready-for-use dialysis solution.

14. The method of claim 12, wherein the dialysis precursor composition consist of the anhydrous glucose powder, the dry acid powder, the anhydrous calcium chloride powder, the hydrated magnesium chloride powder, and a potassium salt.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) A wide variety of different combinations and partitions of dry powder components of normal dialysis solutions like potassium chloride, magnesium chloride, calcium chloride, glucose, sodium chloride, sodium bicarbonate, dry acids like citric acid, glucono-δ-lactone, etc. were prepared and put in a forced stability study. Matters like caking, lump formation, discoloration and dissolution rate were investigated after 1 month, 4 months and 10 months storage time.

(2) It was identified that, as expected earlier, sodium bicarbonate needs to be separated from the other components due to carbon dioxide formation, calcium carbonate precipitation, and magnesium carbonate precipitation. However, when combining the remaining components of a normal dialysis solution the crystalline water attached to glucose and calcium chloride caused problems with caking and lump formation within the powder compositions and discoloration of glucose. By replacing glucose with anhydrous glucose and by replacing calcium chloride dihydrate with anhydrous calcium chloride, or another calcium salt not containing any crystalline water, the powder composition remained stable, free flowing and no discoloration evolved. Thus, in order to make sure that a stable composition is provided the container material used for storing the composition should be moisture-resistant and not allow passage of an amount equal to or above the amount which equals the crystalline water normally attached with the calcium salt. This is achieved with a container material having a water vapour transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH.

(3) In another embodiment said container material has a water vapour transmission rate less than 0.2 g/m.sup.2/d at 38° C./90% RH.

(4) In another embodiment said container material has a water vapour transmission rate between 0.05-0.3 g/m.sup.2/d at 38° C./90% RH.

(5) In even another embodiment said container material has a water vapour transmission rate between 0.05-0.2 g/m.sup.2/d at 38° C./90% RH. In another embodiment said container material has a water vapour transmission rate between 0.1-0.3 g/m.sup.2/d at 38° C./90% RH.

(6) In even another embodiment said container material has a water vapour transmission rate between 0.1-0.2 g/m.sup.2/d at 38° C./90% RH.

(7) According to the invention said dialysis acid precursor composition consists of powder components comprising glucose, at least one dry acid and at least one calcium salt, and optionally potassium salt, and magnesium salt, wherein said glucose and said at least one calcium salt are present as anhydrous components in said dialysis acid precursor composition within the moisture-resistant container.

(8) In other embodiments of the present invention said at least one dry acid is selected from the group comprising lactic acid, citric acid, gluconic acid, glucono-δ-lactone, N-acetyl cystein and α-lipoic acid. Thus, a combination of dry acids may be used within said dialysis acid precursor composition, and by providing a combination of different dry acids, other functions and effects, in addition to said acidic function, may be provided, like for instance antioxidative effects (as with gluconic acid, glucono-δ-lactone, N-acetyl cystein and α-lipoic acid), anticoagulation effects (as with citric acid) and so forth.

(9) In even further embodiments said at least one calcium salt in said dialysis acid precursor composition, is selected from the group comprising anhydrous calcium chloride, calcium gluconate, calcium citrate (tricalcium dicitrate), calcium lactate, and calcium α-ketoglutarate. Also here a combination of different calcium salts may be used in order to tailor specific add-on features, like antioxidative effects from calcium gluconate, or anticoagulation effects from calcium citrate, and so forth.

(10) In one embodiment said at least one calcium salt in said dialysis acid precursor composition comprises anhydrous calcium chloride. By using anhydrous calcium chloride in a dry dialysis acid precursor composition, the anhydrous component will act as desiccant if any water would transport into the bag.

(11) In one embodiment said at least one calcium salt in said dialysis acid precursor composition is selected from the group consisting of calcium gluconate, calcium citrate and calcium lactate.

(12) In other embodiments, in which magnesium salt is present, said magnesium salt in said dialysis acid precursor composition, is at least one chosen from the group comprising magnesium chloride with different degree of hydration, e.g. magnesium chloride hexahydrate or magnesium chloride dihydrate. In one embodiment said dialysis precursor composition is provided in a specific amount and is configured to be mixed with a prescribed volume of water within said moisture-resistant container to provide a dialysis acid concentrate solution. Thus, said moisture-resistant container is configured to receive and dispense solutions up to said prescribed volume.

(13) In one embodiment said prescribed volume may be within the range of from 0.3 to 8 L.

(14) In another embodiment said prescribed volume may be within the range of from 5-20 L.

(15) In even another embodiment said prescribed volume may be within the range of 300-1000 L.

(16) Further, in one embodiment said dialysis acid concentrate solution is configured and provided to be diluted within the range of 1:30 to 1:200 with water, a sodium containing concentrate, and a bicarbonate containing concentrate.

(17) The present invention further concerns a method of providing a dialysis acid concentrate solution. Said dialysis acid concentrate solution is further intended to be mixed with additional water, a sodium containing concentrate, and a bicarbonate containing concentrate to provide a ready-for-use dialysis solution. According to the invention said method comprises (a) providing a dialysis precursor composition comprising glucose, at least one dry acid, and at least one calcium salt, optionally potassium salt, and magnesium salt, wherein said glucose and said at least one calcium salt are present as anhydrous components in said dialysis acid precursor composition, (b) providing said dialysis precursor composition in a sealed, moisture-resistant container with a water vapour transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH, and (c) adding a prescribed volume of water to said dialysis precursor composition in said container and mixing thereof, thereby providing said dialysis acid concentrate as a solution.

(18) Glucose is provided in such a quantity in said moisture-resistant container that a concentration of 30-400 g/L is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(19) Said dry acid is provided in such a quantity in said moisture-resistant container that a concentration within the range of 60-800 mEq/L H.sup.+ (acid) is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(20) Further, said at least one calcium salt is provided in such a quantity in said moisture-resistant container that a concentration within the range of 30-500 mM calcium ions is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(21) If present, said magnesium salt is provided in such a quantity in said moisture-resistant container that a concentration within the range of 7.5-150 mM magnesium ions is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(22) If present, potassium salt is provided in such a quantity in said moisture-resistant container that a concentration within the range of 0-800 mM potassium ions is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(23) In one embodiment said dry dialysis acid precursor composition comprises the different components in such an amount that, when said dry dialysis acid precursor composition has been dissolved and mixed with water, a sodium concentrate, and a bicarbonate concentrate, it provides a ready-for-use dialysis solution comprising from about 130-150 mM of sodium ions, from about 0 to 4 mM of potassium ions, from about 1-2.5 mM of calcium ions, from about 0.25 to 1 mM of magnesium ions, from about 0 to 2% (g/l) glucose from about 85 to 134 mM chloride ions, from about 2 to 4 mEq/L acid, and from about 25 to 45 mEq/L bicarbonate ions.

(24) Thus, the present invention provides a prepackaged container with a dry dialysis acid precursor composition for use during preparation of a dialysis acid concentrate solution and for mixing with water, a sodium containing concentrate, and a bicarbonate containing concentrate into a ready-for-use dialysis solution, wherein said dialysis acid precursor composition consists of powder components comprising glucose, at least one dry acid and at least one calcium salt. Optionally said dialysis acid precursor composition further comprises potassium salts, and magnesium salts. According to the invention said glucose and said at least one calcium salt is present as anhydrous component in said dialysis acid precursor composition and said dialysis acid precursor composition is sealed in a moisture-proof container with a water vapour transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH.

EXAMPLES

(25) By way of example, and not limitation, the following examples identify a variety of dialysis acid precursor compositions pursuant to embodiments of the present invention.

(26) In examples 1-4, the tables show the content of dialysis acid precursor compositions for dilution 1:35. The prescribed volume of each dialysis acid concentrate solution (DACS in tables below) is 5.714 L, and the final volume of each ready-for-use dialysis solution (RFUDS in tables below) is 200 L.

Example 1

(27) TABLE-US-00001 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Potassium chloride 29.81 70 2 Magnesium chloride 20.33 17.5 0.5 hexahydrate Calcium gluconate 129.1 52.5 1.5 Citric acid 38.42 35 1 Glucose anhydrous 200 194 5.55

Example 2

(28) TABLE-US-00002 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Magnesium 20.33 17.5 0.5 chloride hexahydrate Calcium gluconate 129.1 52.5 1.5 Citric acid 38.42 35 1 Glucose anhydrous 400 388.8 11.11

Example 3

(29) TABLE-US-00003 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Potassium chloride 29.81 70 2 Magnesium chloride 20.33 17.5 0.5 hexahydrate Calcium chloride 33.30 52.5 1.5 anhydrous Glucono-delta-lactone 142.5 140 4 Glucose anhydrous 200 194 5.55

Example 4

(30) TABLE-US-00004 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Potassium chloride 29.81 70 2 Magnesium chloride 20.33 17.5 0.5 hexahydrate Calcium chloride 33.30 52.5 1.5 anhydrous Citric acid 38.42 35 1 Glucose anhydrous 200 194 5.55
In examples 5 and 6, the tables show the content of a dry acid precursor composition for dilution 1:200. The prescribed volume of each dialysis acid concentrate solution (DACS in tables below) is 1 L, and the final volume of each ready-for-use dialysis solution (RFUDS in tables below) is 200 L.

Example 5

(31) TABLE-US-00005 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Magnesium chloride 20.33 100 0.5 hexahydrate Calcium gluconate 150.6 350 1.75 Citric acid 38.42 200 1 Glucose anhydrous 200 1110 5.55

Example 6

(32) TABLE-US-00006 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Potassium chloride 59.64 800 4 Magnesium chloride 20.33 100 0.5 hexahydrate Calcium chloride 22.22 200 1 anhydrous Citric acid 38.42 200 1 Glucose anhydrous 200 1110 5.55

(33) While the invention has been described in connection with what is presently considered to be the most practical embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalents included within the spirit and the scope of the appended claims.