Dialysis precursor composition product

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. The dialysis acid precursor composition consists of powder components comprising glucose, at least one dry acid and at least one magnesium salt, and optionally potassium salt, and calcium salt. According to the invention the glucose and the at least one magnesium salt, are present as anhydrous components in the dialysis acid precursor composition.

Claims

1. A dialysis acid precursor composition product comprising: an anhydrous powdered composition including a sodium containing concentrate, a bicarbonate containing concentrate, a dry acid and a magnesium salt, a calcium salt in a hydrate form, and a sealed moisture-resistant container including a single chamber housing the anhydrous powdered composition and the calcium salt in the hydrate form, wherein the container has 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 product remains stable for at least six months.

2. The dialysis acid precursor composition product of claim 1, wherein the dry acid includes at least one of lactic acid, citric acid, gluconic acid, glucono-δ-lactone, N-acetyl cysteine and α-lipoic acid.

3. The dialysis acid precursor composition product of claim 1, wherein the magnesium salt includes at least one of anhydrous magnesium chloride, magnesium gluconate, magnesium citrate, magnesium lactate, and magnesium α-ketoglutarate.

4. The dialysis acid precursor composition product of claim 1, wherein the calcium salt in the hydrate form includes at least one of calcium chloride, calcium gluconate, calcium citrate, calcium lactate, and calcium α-ketoglutarate in a hydrate form.

5. The dialysis acid precursor composition product of claim 1, wherein the water vapor transmission rate is less than 0.2 g/m.sup.2/d at 38° C./90% RH.

6. The dialysis acid precursor composition product of claim 1, wherein the water vapor transmission rate is greater than 0.1 g/m.sup.2/d at 38° C./90% RH.

7. The dialysis acid precursor composition product of claim 1, wherein the container is configured to receive water which mixes with the anhydrous powdered composition and the calcium salt in the hydrate form in the container to provide a dialysis acid concentrate solution.

8. The dialysis acid precursor composition product of claim 7, wherein the magnesium salt is in a quantity such that a concentration of 7.5-50 mM magnesium ions is provided in the dialysis acid concentrate solution.

9. The dialysis acid precursor composition product of claim 7, wherein the calcium salt in the hydrate form is provided in a quantity such that a concentration of 300-500 mM calcium ions is provided in the dialysis acid concentrate solution.

10. The dialysis acid precursor composition product of claim 7, wherein the dry acid is in a quantity such that a concentration of 60-800 mEq/L H+(acid) is provided in the dialysis acid concentrate solution.

11. The dialysis acid precursor composition product of claim 7, wherein the anhydrous powdered composition includes glucose in a quantity such that a concentration of 30-400 g/L is provided in the dialysis acid concentrate solution.

12. The dialysis acid precursor composition product of claim 1, which is configured to remain stable for at least 6 months when incubated in 30° C./65% RH or 40° C./75% RH.

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-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 magnesium 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 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 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 glucose, at least one dry acid and at least one magnesium salt, and optionally potassium salt, and calcium salt, wherein the glucose and the at least one magnesium salt 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 of lactic acid, citric acid, gluconic acid, glucono-δ-lactone, N-acetyl cysteine and α-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, apart from the acidic function, may be provided, like for instance antioxidative effects (as with gluconic acid, glucono-δ-lactone, N-acetyl cysteine and α-lipoic acid), anticoagulation effects (as with citric acid) and so forth.

(10) In even further embodiments the at least one magnesium salt in the 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 the at least one magnesium salt in the 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, the calcium salt in the 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, the calcium salt is at least one chosen from the group comprising of anhydrous calcium chloride, calcium gluconate, calcium citrate and calcium lactate.

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

(15) 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.

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

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

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

(19) Further, in one embodiment the 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.

(20) 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, a sodium containing concentrate, and a bicarbonate containing concentrate to provide a ready-for-use dialysis solution. According to the invention such a method comprises (a) providing a dialysis precursor composition comprising glucose, at least one dry acid, and at least one magnesium salt, optionally potassium salt, and calcium salt, wherein the glucose and the at least one magnesium salt 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/m.sup.2/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.

(21) Glucose is provided in such a quantity in the 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 the moisture-resistant container.

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

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

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

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

(26) 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, 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 20 to 40 mEq/L bicarbonate ions.

(27) 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 the dialysis acid precursor composition consist of powder components comprising glucose, at least one dry acid and at least one magnesium salt. Optionally the dialysis acid precursor composition further comprises potassium salts, and calcium salts. According to the invention the glucose and the at least one magnesium 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.

(28) 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

(29) 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.

(30) 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

(31) TABLE-US-00001 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) 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 5.55

Example 2

(32) TABLE-US-00002 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) 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 5.55

Example 3

(33) TABLE-US-00003 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) 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 5.55

Example 4

(34) TABLE-US-00004 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) 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 5.55

Example 5

(35) TABLE-US-00005 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) 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 5.55

(36) In example 6-9, 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 6

(37) TABLE-US-00006 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Potassium chloride 59.64 800 4 Magnesium gluconate 41.46 100 0.5 Calcium chloride 51.45 350 1.75 dihydrate Citric acid 38.42 200 1 Glucose anhydrous 200 1111 5.55

Example 7

(38) TABLE-US-00007 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Trimagnesium dicitrate 15.04 33.4 0.167 Calcium gluconate 150.6 350 1.75 Citric acid 38.42 200 1 Glucose anhydrous 200 1111 5.55

Example 8

(39) TABLE-US-00008 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Potassium chloride 29.82 400 2 Magnesium lactate 20.24 100 0.5 Calcium chloride 44.10 300 1.5 dihydrate Glucono-delta-lactone 35.63 200 1 Citric acid 30.74 160 0.8 Glucose anhydrous 200 1111 5.55

Example 9

(40) TABLE-US-00009 Amount Conc in Conc in Ingredient (g) DACS (mM) RFUDS (mM) Potassium chloride 59.64 800 4 Magnesium gluconate 41.46 100 0.5 Calcium chloride 22.22 200 1 dihydrate Citric acid 38.42 200 1 Glucose anhydrous 200 1111 5.55

(41) Tests

(42) 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.

(43) Methods

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

(45) Composition 1

(46) The amount of powder components of potassium chloride, anhydrous magnesium chloride, calcium chloride dihydrate, anhydrous glucose, and citric acid 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.

(47) Composition 2

(48) The amount of powder components of potassium chloride, anhydrous magnesium chloride, anhydrous calcium chloride, anhydrous glucose, and citric acid necessary to produce 230 L of dialysis fluid were filled into 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.

(49) Comparison Composition 3

(50) The amount of powder components of potassium chloride, anhydrous magnesium chloride, calcium chloride dihydrate, anhydrous glucose, and citric acid necessary to produce 230 L of dialysis fluid were filled into 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.

(51) Results

(52) 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.

(53) 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.