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. The dialysis acid precursor composition consists of powder components comprising sodium chloride, at least one dry acid and at least one calcium salt, and optionally potassium salt, magnesium salt, and glucose. In an embodiment, the at least one calcium salt and the optional glucose are present as anhydrous components in the dialysis acid precursor composition.

Claims

1. A ready-for-use dialysis solution comprising: a bicarbonate containing concentrate; and a dialysis acid concentrate solution comprising powder components mixed with water, the powder components comprising (1) a sodium chloride powder, (2) at least one dry acid powder, and (3) an anhydrous calcium chloride powder in a quantity such that a concentration of about 30-125 mM calcium ions is provided in the dialysis acid concentrate solution.

2. The ready-for-use dialysis solution of claim 1, wherein the at least one dry acid is selected from the group comprising lactic acid, citric acid, gluconic acid, glucono--lactone, N-acetyl cysteine and -lipoic acid.

3. The ready-for-use dialysis solution of claim 1, wherein the powder components comprise potassium salt in a quantity such that a concentration of about 0-4 mM potassium ions is provided in the ready-for-use dialysis solution.

4. The ready-for-use dialysis solution of claim 1, wherein the powder components comprise magnesium salt in a quantity such that a concentration of about 0.25-1 mM magnesium ions is provided in the ready-for-use dialysis solution.

5. The ready-for-use dialysis solution of claim 1, wherein the powder components comprise anhydrous glucose in a quantity such that a concentration of about 0-2 g/l glucose is provided in the ready-for-dialysis solution.

6. The ready-for-use dialysis solution of claim 1, wherein the sodium chloride is in a quantity such that a concentration of about 130-150 mM sodium ions is provided in the ready-for-use dialysis solution.

7. The ready-for-use dialysis solution of claim 1, wherein the anhydrous calcium chloride is in a quantity such that a concentration of about 1-2.5 mM calcium ions is provided in the ready-for-use dialysis solution.

8. The ready-for-use dialysis solution of claim 1, wherein the sodium chloride and the anhydrous calcium chloride are in a quantity such that a concentration of about 85-134 mM chloride ions is provided in the ready-for-use dialysis solution.

9. The ready-for-use dialysis solution of claim 1, wherein the at least one dry acid is in a quantity such that a concentration of about 2-4 mEq/L acid is provided in the ready-for-use dialysis solution.

10. The ready-for-use dialysis solution of claim 1, wherein the bicarbonate containing concentrate is in a quantity such that a concentration of about 20-40 mEq/L bicarbonate ions is provided in the ready-for-use dialysis solution.

11. The ready-for-use dialysis solution of claim 1, wherein the ready-for-use dialysis solution is one selected from the group consisting of a dialysis solution, an infusion solution, a replacement solution, a rinsing solution, and a priming solution.

12. A method for forming a ready-for-use dialysis solution, the method comprising: diluting a dialysis acid concentrate solution with a bicarbonate containing concentrate, the dialysis acid concentrate solution comprising powder components mixed with water, the powder components comprising (1) a sodium chloride powder, (2) at least one dry acid powder, and (3) an anhydrous calcium chloride powder in a quantity such that a concentration of about 30-125 mM calcium ions is provided in the dialysis acid concentrate solution.

13. The method of claim 12, wherein the powder components comprise potassium salt in a quantity such that a concentration of about 0-4 mM potassium ions is provided in the ready-for-use dialysis solution.

14. The method of claim 12, wherein the powder components comprise magnesium salt in a quantity such that a concentration of about 0.25-1 mM magnesium ions is provided in the ready-for-use dialysis solution.

15. The method of claim 12, wherein the powder components comprise anhydrous glucose in a quantity such that a concentration of about 0-2 g/l glucose is provided in the ready-for-dialysis solution.

16. The method of claim 12, wherein the sodium chloride is in a quantity such that a concentration of about 130-150 mM sodium ions is provided in the ready-for-use dialysis solution.

17. The method of claim 12, wherein the anhydrous calcium chloride is in a quantity such that a concentration of about 1-2.5 mM calcium ions is provided in the ready-for-use dialysis solution.

18. The method of claim 12, wherein the sodium chloride and the anhydrous calcium chloride are in a quantity such that a concentration of about 85-134 mM chloride ions is provided in the ready-for-use dialysis solution.

19. The method of claim 12, wherein the at least one dry acid is in a quantity such that a concentration of about 2-4 mEq/L acid is provided in the ready-for-use dialysis solution.

20. The method of claim 12, wherein the bicarbonate containing concentrate is in a quantity such that a concentration of about 20-40 mEq/L bicarbonate ions is provided in the ready-for-use dialysis solution.

Description

DETAILED DESCRIPTION

(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--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 calcium chloride caused problems with caking and lump formation within the powder compositions and discoloration of glucose (if present). 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 vapor transmission rate less than 0.3 g/m.sup.2/d at 38 C./90% RH.

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

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

(10) In even further embodiments the at least one calcium salt in the dialysis acid precursor composition, is selected from the group comprising anhydrous calcium chloride, calcium gluconate, calcium citrate (tricalcium dicitrate), calcium lactate, and calcium -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.

(11) In one embodiment the at least one calcium salt in the 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.

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

(13) In other embodiments, in which magnesium salt is present, the magnesium salt in the 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 the dialysis precursor composition is provided in a specific amount and is configured to be mixed with a prescribed volume of water within the moisture-resistant container to provide a dialysis acid concentrate solution. Thus, the moisture-resistant container is configured to receive and dispense solutions up to the prescribed volume.

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

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

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

(17) Further, in one embodiment the 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.

(18) The present invention further concerns a method of providing a dialysis acid concentrate solution. The 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 the method comprises (a) providing a dialysis precursor composition comprising sodium chloride, at least one dry acid, and at least one calcium salt, optionally potassium salt, magnesium salt, and glucose, wherein the at least one calcium salt and the optional glucose 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 vapor 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 as a solution.

(19) Sodium chloride is provided in such a quantity in the 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 the moisture-resistant container.

(20) The dry acid is provided in such a quantity in the 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 the moisture-resistant container.

(21) Further, the at least one calcium salt is provided in such a quantity in the 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 the moisture-resistant container.

(22) If present, the magnesium salt is provided in such a quantity in the 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 the moisture-resistant container.

(23) If present, potassium salt is provided in such a quantity in the 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 the moisture-resistant container.

(24) If present, glucose is provided in such a quantity in the 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 the moisture-resistant container.

(25) In one embodiment the dry dialysis acid precursor composition comprises the different components in such an amount that, when the 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.

(26) 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 the dialysis acid precursor composition consists of powder components comprising sodium chloride, at least one dry acid and at least one calcium salt. Optionally the dialysis acid precursor composition further comprises potassium salts, magnesium salts, and glucose. According to the invention the at least one calcium salt is present as anhydrous component in the dialysis acid precursor composition and the 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.

EXAMPLES

(27) 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.

(28) 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

(29) 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 chloride 20.33 17.5 0.5 hexahydrate Calcium gluconate 129.1 52.5 1.5 Citric acid 38.42 35 1 Glucose anhydrous 200 194.4 5.55

Example 2

(30) TABLE-US-00002 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1169 3500 100 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 400 388.8 11.11

Example 3

(31) 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 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 200 194.4 5.55

Example 4

(32) 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 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 200 194.4 5.55

(33) In examples 5-7, 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 5

(34) TABLE-US-00005 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1402 4500 100 Potassium chloride 53.68 135 3 Magnesium chloride 24.40 22.5 0.5 hexahydrate Calcium gluconate 129.1 56.25 1.25 Citric acid 46.10 45 1

Example 6

(35) TABLE-US-00006 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1402 4500 100 Magnesium chloride 24.40 22.5 0.5 hexahydrate Calcium gluconate 180.8 78.75 1.75 Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55

Example 7

(36) TABLE-US-00007 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Sodium chloride 1402 4500 100 Potassium chloride 71.57 180 4 Magnesium chloride 24.40 22.5 0.5 hexahydrate Calcium chloride 26.64 45 1 anhydrous Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55

(37) 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.