Dialysis precursor composition

Abstract

A dialysis acid precursor assembly including: a bicarbonate containing concentrate and a dialysis acid concentrate solution including powder components mixed with water. The powder components include (1) a sodium chloride powder, (2) at least one dry acid powder, and (3) a magnesium chloride 4.5-hydrate (MgCl.sub.2.4.5H.sub.2O) powder in a quantity such that a concentration of about 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution.

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 a sodium chloride powder, at least one dry acid powder, an anhydrous calcium chloride powder in a quantity such that a concentration of 30-125 mM calcium ions is provided in the dialysis acid concentrate solution, and a magnesium chloride 4.5-hydrate (MgCl.sub.2.4.5H.sub.2O) powder in a quantity such that a concentration of about 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution, wherein the at least one dry acid is selected from the group consisting of lactic acid, citric acid, gluconic acid, glucono--lactone, N-acetyl cysteine and -lipoic acid.

2. 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.

3. The ready-for-use dialysis solution of claim 1, wherein the powder components comprise the anhydrous calcium chloride powder in a quantity such that a concentration of about 1-2.5 mM calcium 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 glucose in a quantity such that a concentration of about 0-2 g/l glucose is provided in the ready-for-dialysis solution.

5. 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.

6. The ready-for-use dialysis solution of claim 1, wherein the MgCl.sub.2.4.5H.sub.2O is in a quantity such that a concentration of about 0.25-1 mM magnesium ions is provided in the ready-for-use dialysis solution.

7. The ready-for-use dialysis solution of claim 1, wherein the sodium chloride and the MgCl.sub.2.4.5H.sub.2O are in a quantity such that a concentration of about 85-134 mM chloride ions is provided in the ready-for-use dialysis solution.

8. 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.

9. 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.

10. 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.

11. 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 a sodium chloride powder, at least one dry acid powder, an anhydrous calcium chloride powder in a quantity such that a concentration of 30-125 mM calcium ions is provided in the dialysis acid concentrate solution, and a magnesium chloride 4.5-hydrate (MgCl.sub.2.4.5H.sub.2O) powder in a quantity such that a concentration of about 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution, wherein the at least one dry acid is selected from the group consisting of lactic acid, citric acid, gluconic acid, glucono--lactone, N-acetyl cysteine and -lipoic acid.

12. The method of claim 11, 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.

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

14. The method of claim 11, wherein the powder components comprise glucose in a quantity such that a concentration of about 0-2 g/l glucose is provided in the ready-for-dialysis solution.

15. The method of claim 11, 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.

16. The method of claim 11, wherein the MgCl.sub.2.4.5H.sub.2O is in a quantity such that a concentration of about 0.25-1 mM magnesium ions is provided in the ready-for-use dialysis solution.

17. The method of claim 11, wherein the sodium chloride and the MgCl.sub.2.4.5H.sub.2O are in a quantity such that a concentration of about 85-134 mM chloride ions is provided in the ready-for-use dialysis solution.

18. The method of claim 11, 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.

19. The method of claim 11, 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 six crystalline water (hexahydrate) 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 magnesium chloride 4.5-hydrate, the powder composition unexpectedly 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 difference in crystalline water between hexahydrate and 4.5-hydrate magnesium salt. This is achieved with a container material having a water vapour transmission rate less than 0.2 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 0.1 g/m.sup.2/d at 38 C./90% RH.

(4) In another embodiment said container material as ha water vapour transmission rate of more than 0.05 g/m.sup.2/d at 38 C./90% RH.

(5) In 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.

(6) In even another embodiment said container material has a water vapour transmission rate between 0.05-0.1 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 sodium chloride, at least one dry acid and at least one magnesium salt, and optionally potassium salt, calcium salt, and glucose, wherein said optional glucose is present as anhydrous component in said dialysis acid precursor composition and wherein said at least one magnesium salt is present as magnesium chloride 4.5-hydrate (MgCl.sub.2.4.5H.sub.2O) 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--lactone, N-acetyl cystein and -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 citric acid, gluconic acid, glucono--lactone, N-acetyl cystein and -lipoic acid), anticoagulation effects (as with citric acid) and so forth.

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

(10) In another embodiment, said calcium salt is calcium chloride dihydrate (CaCl.sub.2.2H.sub.2O).

(11) 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.

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

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

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

(15) 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.

(16) 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 said 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 optional glucose is present as anhydrous component in said dialysis acid precursor composition, and wherein said at least one magnesium salt is present as magnesium chloride 4.5-hydrate (MgCl.sub.2.4.5H.sub.2O) (b) providing said dialysis precursor composition in a sealed, moisture-resistant container with a water vapour transmission rate less than 0.2 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.

(17) 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.

(18) 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.

(19) 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.

(20) 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.

(21) 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.

(22) 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.

(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 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.

(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 and a bicarbonate containing concentrate into a ready-for-use dialysis solution, wherein said dialysis acid precursor composition consists 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 magnesium chloride 4.5-hydrate (MgCl.sub.2.4.5H.sub.2O) 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 0.2 g/m.sup.2/d at 38 C./90% RH.

(25) When using magnesium chloride 4.5-hydrate (MgCl.sub.2.4.5H.sub.2O) powder in a dry dialysis acid precursor composition, the dry dialysis acid precursor composition unexpectedly remain stable, lump free and without glucose degradation.

EXAMPLES

(26) 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.

(27) 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 fmal volume of each ready-for-use dialysis solution (RFUDS in tables below) is 200 L.

Example 1

(28) TABLE-US-00001 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Magnesium chloride 4.5-hydrate 17.63 17.5 0.5 Calcium chloride dihydrate 44.10 52.5 1.5 Citric acid 38.42 35 1 Glucose anhydrous 200 194.4 5.55

Example 2

(29) TABLE-US-00002 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Magnesium chloride 4.5-hydrate 17.63 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

(30) TABLE-US-00003 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Magnesium chloride 4.5-hydrate 17.63 17.5 0.5 Calcium chloride dihydrate 44.10 52.5 1.5 Glucono-delta-lactone 35.63 35 1 Citric acid 30.73 28 0.8 Glucose anhydrous 200 194.4 5.55

Example 4

(31) TABLE-US-00004 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1169 3500 100 Potassium chloride 29.81 70 2 Magnesium chloride 4.5-hydrate 17.63 17.5 0.5 Calcium chloride anhydrous 33.30 52.5 1.5 Glucono-delta-lactone 142.5 140 4 Glucose anhydrous 200 194.4 5.55

(32) In example 5-9, 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 fmal volume of each ready-for-use dialysis solution (RFUDS in tables below) is 240 L.

Example 5

(33) TABLE-US-00005 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 71.57 180 4 Magnesium chloride 4.5-hydrate 21.16 22.5 0.5 Calcium chloride dihydrate 61.74 78.75 1.75 Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55

Example 6

(34) TABLE-US-00006 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 53.68 135 3 Magnesium chloride 4.5-hydrate 21.16 22.5 0.5 Calcium gluconate 129.12 56.25 1.25 Citric acid 46.10 45 1

Example 7

(35) TABLE-US-00007 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1401.7 4500 100 Magnesium chloride 4.5-hydrate 21.16 22.5 0.5 Calcium gluconate 180.77 78.75 1.75 Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55

Example 8

(36) TABLE-US-00008 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 35.78 90 2 Magnesium chloride 4.5-hydrate 21.16 22.5 0.5 Calcium chloride dihydrate 52.92 67.5 1.5 Glucono-delta-lactone 42.75 45 1 Citric acid 36.88 36 0.8 Glucose anhydrous 240 250 5.55

Example 9

(37) TABLE-US-00009 Conc in Conc in Amount DACS RFUDS Ingredient (g) (mM) (mM) Sodium chloride 1401.7 4500 100 Potassium chloride 71.57 180 4 Magnesium chloride 4.5-hydrate 21.16 22.5 0.5 Calcium chloride anhydrous 26.64 45 1 Citric acid 46.10 45 1 Glucose anhydrous 240 250 5.55

(38) Tests

(39) 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.

(40) Methods

(41) Plastic films were welded into bags with 1 compartment.

(42) Composition 1

(43) The amount of powder components of potassium chloride, magnesium chloride 4.5-hydrate, 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/m.sup.2/d at 38 C./90% RH. The bags were sealed and incubated in 30 C., 65% RH, and in 40 C., 75% RH, respectively.

(44) Composition 2

(45) The amount of powder components of potassium chloride, magnesium chloride 4.5-hydrate, 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/m.sup.2/d at 38 C./90% RH. The bags were sealed and incubated in 30 C., 65% RH, and in 40 C., 75% RH, respectively.

(46) Comparison Composition 3

(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 2.7 g/m.sup.2/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) Comparison Composition 4

(49) The amount of powder components of potassium chloride, magnesium chloride hexahydrate, calcium chloride dihydrate, anhydrous glucose, citric acid, and sodium chloride necessary to produce 230 L of dialysis fluid were filled into glass bottles, thus with no water vapor transmission. The bags were sealed and incubated in 30 C., 65% RH, and in 40 C., 75% RH, respectively.

(50) Comparison Composition 5

(51) 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 2.7 g/m.sup.2/d at 38 C./90% RH. The bags were sealed and incubated in 40 C., 75% RH.

(52) Results

(53) Compositions 1 and 2 have proven to stay stable for at least one year, while comparison compositions 3 and 4 failed due to formation of brown lumps after less than 1 month. Comparison composition 5 also failed due to formation of brown lumps after 1 to 3 months.

(54) 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.