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 and a bicarbonate containing concentrate into a ready-for-use dialysis solution. Said dialysis acid precursor composition consist of powder components comprising sodium chloride, at least one dry acid and at least one magnesium salt, and optionally potassium salt, calcium salt, and glucose. According to the invention said at least one magnesium salt and said optional glucose, 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 and a bicarbonate containing concentrate into a ready-for-use dialysis solution, the dialysis acid precursor composition comprising: powder components comprising a sodium chloride powder, at least one dry acid powder, at least one magnesium salt powder, at least one calcium salt powder selected from the group consisting of calcium chloride monohydrate, anhydrous calcium chloride, calcium gluconate, and calcium α-ketoglutarate, and a glucose powder, wherein the at least one magnesium salt powder is in a quantity such that a concentration of 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution, wherein the at least one magnesium salt and the glucose are present as anhydrous components in the dialysis acid precursor composition, wherein at least one of the sodium chloride, the at least one dry acid, or the at least one calcium salt is present as a non-anhydrous component, and wherein the dialysis acid precursor composition is sealed in a moisture-resistant container with a water vapor transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH, and wherein the dialysis acid precursor composition does not comprise acetic acid or acetate, and does not comprise lactic acid or lactate.

2. A dialysis precursor composition according to claim 1, wherein said at least one dry acid is selected from a group comprising 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 at least one magnesium salt in said dialysis acid precursor composition is selected from a group comprising anhydrous magnesium chloride, magnesium gluconate, magnesium citrate, and magnesium α-ketoglutarate.

4. A dialysis precursor composition according to claim 1, wherein said moisture-resistant container has a water vapor transmission rate of less than 0.2 g/m.sup.2/d at 38° C./90% RH.

5. A dialysis precursor composition according to claim 1, wherein said moisture-resistant container has a water vapor transmission rate of more than 0.1 g/m.sup.2/d at 38° C./90% RH.

6. 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.

7. The dialysis acid precursor composition according to claim 1, wherein the dialysis precursor composition is for preparing a dialysis acid concentrate solution.

8. The dialysis acid precursor composition according to claim 1, wherein the dialysis acid precursor composition is for preparing a dialysis solution, an infusion solution, a replacement solution, a rinsing solution or a priming solution.

9. The dialysis acid precursor composition of claim 1, wherein the powder components include at least one of a potassium salt powder and a calcium salt powder which are anhydrous.

10. The dialysis precursor composition of claim 1, wherein the sodium chloride powder is in a quantity such that a concentration of 2.55-5.5 M sodium chloride is provided in the dialysis acid concentrate solution.

11. The dialysis precursor composition of claim 1, wherein the at least one dry acid powder is in a quantity such that a concentration of 60-200 mEq/L H.sup.+ (acid) is provided in the dialysis acid concentrate solution.

12. The dialysis precursor composition of claim 1, wherein the glucose powder is in a quantity such that a concentration of 0-100 g/L is provided in the dialysis acid concentrate solution.

13. A method of providing a dialysis acid concentrate solution for dilution with water and a bicarbonate containing concentrate to produce a ready-for-use dialysis solution, the method comprising: providing a dialysis precursor composition comprising a sodium chloride powder, at least one dry acid powder, at least one magnesium salt powder, at least one calcium salt powder selected from the group consisting of calcium chloride monohydrate, anhydrous calcium chloride, calcium gluconate, and calcium α-ketoglutarate, and a glucose powder, wherein the at least one magnesium salt powder is in a quantity such that a concentration of 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution, and wherein the at least one magnesium salt and the glucose are present as anhydrous components in the dialysis acid precursor composition, and wherein at least one of the sodium chloride, the at least one dry acid, or the at least one calcium salt is present as a non-anhydrous component; providing the dialysis precursor composition in a sealed, moisture-resistant container with a water vapor transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH; and adding a prescribed volume of water to the dialysis precursor composition in the container and mixing thereof, thereby providing the dialysis acid concentrate as a solution, wherein the dialysis acid precursor composition does not comprise acetic acid or acetate, and does not comprise lactic acid or lactate.

14. The method of claim 13, wherein the dialysis precursor composition comprises a potassium salt powder.

15. An apparatus comprising: a powdered dialysis precursor composition including a sodium chloride powder, a dry acid powder, a magnesium salt powder, and a glucose powder, each of which are present as an anhydrous component of the composition, and at least one calcium salt powder selected from the group consisting of calcium chloride monohydrate, calcium gluconate, and calcium α-ketoglutarate, wherein the magnesium salt powder is in a quantity such that a concentration of 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution, and wherein the at least one calcium salt is present as a non-anhydrous component; and a moisture-resistant container having a water vapor transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH containing the powered dialysis precursor, wherein the dialysis acid precursor composition does not comprise acetic acid or acetate, and does not comprise lactic acid or lactate.

16. The apparatus of claim 15, wherein the dry acid includes at least one of citric acid, gluconic acid, glucono-δ-lactone, N-acetyl cystein and α-lipoic acid.

17. The apparatus of claim 15, wherein said anhydrous magnesium salt includes at least one of magnesium chloride, magnesium gluconate, magnesium citrate, and magnesium α-ketoglutarate.

18. The apparatus of claim 15, wherein said water vapor transmission rate is less than 0.2 g/m.sup.2/d at 38° C./90% RH.

19. The apparatus of claim 15 wherein said water vapor transmission rate is more than 0.1 g/m.sup.2/d at 38° C./90% RH.

20. The apparatus of claim 15, wherein said powdered dialysis precursor composition is configured to mix with water within said moisture-resistant container.

21. A method comprising: forming a dialysis precursor powder composition including a sodium chloride powder, a dry acid powder, a magnesium salt powder, and a glucose powder, wherein each is present as an anhydrous component in the composition, and at least one calcium salt powder selected from the group consisting of calcium chloride monohydrate, calcium gluconate, and calcium α-ketoglutarate, wherein the at least one calcium salt is present as a non-anhydrous component, and wherein the magnesium salt powder is in a quantity such that a concentration of 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution, and sealing the dialysis precursor composition in a moisture-resistant container having a water vapor transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH, wherein the dialysis acid precursor composition does not comprise acetic acid or acetate, and does not comprise lactic acid or lactate.

22. The method of claim 21, further comprising: mixing water and said dialysis precursor composition in said container to form a dialysis acid concentrate solution, and diluting the dialysis acid concentrate solution with water and a bicarbonate containing concentrate to produce at least one of a dialysis solution, an infusion solution, a replacement solution, a rinsing solution and a priming solution.

23. The method of claim 22, wherein the dialysis precursor powder composition includes a potassium salt powder.

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, 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 magnesium chloride caused problems with caking and lump formation within the powder compositions and discoloration of glucose (if present). By replacing magnesium chloride hexahydrate with anhydrous magnesium chloride, or another magnesium 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 magnesium salt. This is achieved with a container material having a water vapor 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 vapor 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 vapor 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 vapor transmission rate between 0.05-0.2 g/m.sup.2/d at 38° C./90% RH.

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

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

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

(9) In other embodiments of the present invention said at least one dry acid is selected from the group comprising of 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, apart from said acidic function, may be provided, like for instance antioxidative effects (as with citric acid, gluconic acid, glucono-δ-lactone, N-acetyl cystein and α-lipoic acid), anticoagulation effects (as with citric acid) and so forth.

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

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

(12) In other embodiments, in which calcium salt is present, said calcium salt in said dialysis acid precursor composition, is at least one chosen from the group comprising of calcium chloride dihydrate, calcium chloride monohydrate, anhydrous calcium chloride, calcium gluconate, calcium citrate, calcium lactate, and calcium α-ketoglutarate. Thus, also here a combination of different calcium salts may be used.

(13) In another embodiment, said calcium salt is at least one chosen from the group comprising of anhydrous calcium chloride, calcium gluconate, calcium citrate, calcium lactate, and calcium α-ketoglutarate.

(14) In another embodiment, said calcium salt is at least one chosen from the group comprising of calcium gluconate, calcium citrate and calcium lactate.

(15) 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.

(16) In one embodiment said prescribed volume may be within the range of from 1 to 8 L.

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

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

(19) Further, in one embodiment said dialysis acid concentrate solution is configured and provided to be diluted within the range of 1:30 to 1:50 with water and a bicarbonate concentrate.

(20) 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 and a bicarbonate concentrate to produce a ready-for-use dialysis solution. According to the invention such a method comprises (a) providing a dialysis precursor composition comprising sodium chloride, at least one dry acid, and at least one magnesium salt, optionally potassium salt, calcium salt, and glucose, wherein said at least one magnesium salt and said optional glucose 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 vapor 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.

(21) Sodium chloride is provided in such a quantity in said moisture-resistant container that a concentration within the range of 2.55-5.5 M sodium chloride is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(22) Said dry acid is provided in such a quantity in said moisture-resistant container that a concentration within the range of 60-200 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.

(23) Further, said at least one magnesium salt is provided in such a quantity in said moisture-resistant container that a concentration within the range of 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(24) If present, said calcium salt is provided in such a quantity in said moisture-resistant container that a concentration within the range of 30-125 mM calcium ions is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(25) If present, potassium salt is provided in such a quantity in said moisture-resistant container that a concentration within the range of 0-200 mM potassium ions is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(26) If present, glucose is provided in such a quantity in said moisture-resistant container that a concentration within the range of 0-100 g/L is provided in the dialysis acid concentrate solution when a prescribed volume of water has entered into said moisture-resistant container.

(27) 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 and bicarbonate 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 20 to 40 mEq/L bicarbonate ions.

(28) 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 and a bicarbonate containing concentrate into a ready-for-use dialysis solution, wherein said dialysis acid precursor composition consist of powder components comprising sodium chloride, at least one dry acid and at least one magnesium salt. Optionally said dialysis acid precursor composition further comprises potassium salts, calcium salts, and glucose. According to the invention said at least one magnesium 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 vapor transmission rate less than 0.3 g/m.sup.2/d at 38° C./90% RH.

(29) By using anhydrous magnesium chloride powder in a dry dialysis acid precursor composition, the anhydrous component will act as desiccants if any water would be transported into the bag.

EXAMPLES

(30) 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.

(31) In examples 1-5, 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

(32) TABLE-US-00001 Amount Conc in Conc in Ingredient (g) DACS(mM) RFUDS(mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Magnesium gluconate 41.46 17.5 0.5 Calcium chloride 44.10 52.5 1.5 dihydrate Citric acid 38.42 35 1 Glucose anhydrous 200 194.4 5.55

Example 2

(33) TABLE-US-00002 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Magnesium lactate 20.24 17.5 0.5 Calcium gluconate 129.1 52.5 1.5 Citric acid 38.42 35 1 Glucose anhydrous 200 194.4 5.55

Example 3

(34) TABLE-US-00003 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Trimagnesium dicitrate 15.04 5.83 0.167 Calcium gluconate 129.1 52.5 1.5 Citric acid 38.42 35 1 Glucose anhydrous 200 194.4 5.55

Example 4

(35) TABLE-US-00004 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Trimagnesium dicitrate 15.04 5.83 0.167 Calcium chloride 44.10 52.5 1.5 dihydrate Glucono-delta-lactone 35.63 35 1 Citric acid 30.73 28 0.8 Glucose anhydrous 200 194.4 5.55

Example 5

(36) TABLE-US-00005 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Trimagnesium dicitrate 15.04 5.83 0.167 Calcium chloride 33.30 52.5 1.5 anhydrous Glucono-delta-lactone 142.5 140 4 Glucose anhydrous 200 194.4 5.55

(37) In example 6-10, the tables show the content of a dry acid precursor composition for dilution 1:45. The prescribed volume of each dialysis acid concentrate solution (DACS in tables below) is 5, 33 L, and the final volume of each ready-for-use dialysis solution (RFUDS in tables below) is 240 L.

Example 6

(38) TABLE-US-00006 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 71.57 180 4 Magnesium gluconate 49.75 22.5 0.5 Calcium chloride 61.74 78.75 1.75 dihydrate Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55

Example 7

(39) TABLE-US-00007 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 53.68 135 3 Magnesium lactate 24.29 22.5 0.5 Calcium gluconate 129.12 56.25 1.25 Citric acid 46.10 45 1

Example 8

(40) TABLE-US-00008 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1401.7 4500 100 Trimagnesium dicitrate 18.04 7.50 0.167 Calcium gluconate 180.77 78.75 1.75 Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55

Example 9

(41) TABLE-US-00009 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 35.78 90 2 Magnesium lactate 24.29 22.5 0.5 Calcium chloride 52.92 67.5 1.5 dihydrate Glucono-delta-lactone 42.75 45 1 Citric acid 36.88 36 0.8 Glucose anhydrous 240 250 5.55

Example 10

(42) TABLE-US-00010 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 71.57 180 4 Magnesium gluconate 49.75 22.5 0.5 Calcium chloride 26.64 45 1 anhydrous Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55
Tests

(43) Tests has been performed to study the stability of different dry powder compositions, both according to embodiments of the present invention as well as comparisons. Parameters like caking, lumping and discoloration were evaluated.

(44) Methods

(45) Plastic films was welded into bags with 1 compartment.

(46) Composition 1

(47) The amount of powder components of potassium chloride, anhydrous magnesium chloride, calcium chloride dihydrate, anhydrous glucose, citric acid, and sodium chloride necessary to produce 230 L of dialysis fluid were filled into the plastic bags, with a water vapor transmission rate of 0.11 g/m2/d at 38° C./90% RH. The bags were sealed and incubated in 30° C., 65% RH, and in 40° C., 75% RH, respectively.

(48) Composition 2

(49) The amount of powder components of potassium chloride, anhydrous magnesium chloride, anhydrous calcium chloride, anhydrous glucose, citric acid, and sodium chloride necessary to produce 230 L of dialysis fluid were filled into the plastic bags, with a water vapor transmission rate of 0.11 g/m2/d at 38° C./90% RH. The bags were sealed and incubated in 30° C., 65% RH, and in 40° C., 75% RH, respectively.

(50) Comparison composition 3

(51) The amount of powder components of potassium chloride, anhydrous magnesium chloride, calcium chloride dehydrate, anhydrous glucose, citric acid, and sodium chloride necessary to produce 230 L of dialysis fluid were filled into the plastic bags, with a water vapor transmission rate of 2.7 g/m2/d at 38° C./90% RH. The bags were sealed and incubated in 30° C., 65% RH, and in 40° C., 75% RH, respectively.

(52) Results

(53) Compositions 1 and 2 have proven to stay stable for at least 6 months, while comparison composition 3 failed due to formation of brown lumps after less than 1 month.

(54) It should be understood that various changes and modifications to the embodiments described herein will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the spirit and scope of the present invention and without diminishing its attendant advantages. It is therefore intended that such changes and modifications be covered by the appended claims.