HK1177890A - Medical solution, method for producing and use thereof - Google Patents

Description

Medical solution, method for the production and use thereof

The application is a divisional application with the application date of 2005, 10 and 14, the application number of 200580021378.8, and the title of the application is "medical solution, its preparation method and application".

Technical Field

The invention relates to medical solutions, a method for the production thereof and the use thereof. The invention relates in particular to medical solutions for dialysis.

Background

Dialysis is the prescribed treatment for patients with renal failure. Waste products are removed from blood by transfer to or replacement of plasma liquid with extracorporeal fluids. The various dialysis techniques using the relevant dialysis fluids may differ, depending on the type of patient they are used. In the case of patients with long-term renal insufficiency, the dialysis technique used is usually an intermittent treatment of several times per week (2-3 times) for several hours (3-5 hours). Waste products, particularly urea, salts and other small molecules, are removed from blood by diffusion through a semi-permeable membrane using a technique known as hemodialysis. Another form of dialysis is peritoneal dialysis. In contrast to hemodialysis, where blood is passed through a dialysis fluid in an extracorporeal dialysis device (artificial kidney), in the case of peritoneal dialysis, the dialysis fluid is introduced into the abdominal cavity (peritoneum) of the patient, wherein the peritoneum acts as a semipermeable membrane.

In the case of patients with acute renal insufficiency, continuous treatment for several weeks throughout the day, i.e. Continuous Renal Replacement Therapy (CRRT), is the prescribed treatment modality. Techniques other than hemodialysis, particularly hemofiltration, are used for this treatment. In the case of hemofiltration, waste products are removed from the blood by convection through a highly permeable membrane. In this way, a large amount of the above waste is removed and also a large amount of molecules. In addition, in the case of hemofiltration, a variable amount of liquid of 1-5 liters per hour is removed from the blood stream. In contrast to hemodialysis, in the case of hemofiltration, it is required that the replacement fluid must be returned to the patient in large amounts. Alternatively, a combination of dialysis and filtration may be used. This is called hemodiafiltration. A particular type of hemodiafiltration is continuous vein-vein hemodiafiltration, abbreviated CVVHDF.

In some cases, hypophosphatemia conditions can occur in patients receiving hemodialysis treatment three times a week and more frequently undergoing CRRT. In the first case, this is mainly due to excessive uptake of phosphate binders, inadequate phosphate administration in parenteral nutrition and continuous removal of phosphorus by dialysis. In the second case, primarily as a result of the initial effective removal of phosphorus from patients with normal renal function and thus normal serum phosphorus levels.

Hypophosphatemia is prevented and treated primarily by oral and intravenous routes, for example by ingestion of phosphorus-rich foods, oral phosphorus preparations, or by intravenous administration of sodium (or potassium) phosphate. However, administration of phosphorus by oral and intravenous routes must be done in a very careful manner, as the precise level of total phosphorus deficiency cannot be determined and it is difficult to determine the exact amount of phosphorus that needs to be administered to a patient. Hyperphosphatemia can occur if too much phosphorus is administered, with serious consequences for the patient, such as hypocalcemia, metastatic calcification and hypotension, while hypophosphatemia cannot be corrected if too little phosphorus is administered.

Solutions containing calcium ions and phosphate salts are used for Total Parenteral Nutrition (TPN). The TPN solution is packaged in a multi-compartment bag with the lipids, amino acids and phosphates, and most of the electrolytes except calcium in the first compartment, and calcium and glucose in the third compartment. The main difference compared to the process of the invention is that the pH of the final ready-to-use solution is much lower than the pH in the solution according to the invention. The TPN solution typically has a pH of 5.2-6.

In US 6,743,191, an alternative infusion fluid is disclosed, comprising 0.2-1.0mM dihydrogenphosphate ion, preferably 0.5-0.9mM, and 1.6-2.6mM, preferably 1.9-2.4 calcium ion. The alternative infusion fluids of this disclosure may be conveniently prepared by dissolving the salt in water in an amount to achieve the desired concentration, which is within the expertise of one skilled in the art. During the manufacturing process, it is necessary to maintain a sterile environment.

In US 6,017,942, an intravenous solution for treating patients with chronic renal failure is disclosed, which solution comprises about 0-20mM phosphate and about 0-10mM calcium, among others. The solution is administered 1-3 times daily.

A problem that arises when introducing phosphorus into the process is the formation of precipitated calcium phosphates and the risk of precipitation is further increased if the fluid contacts final heat sterilisation. The solubility of calcium phosphate depends on the concentration of calcium and phosphate, respectively, and further on the presence of other electrolytes, temperature and pH. If in a TPN solution, there is no risk of precipitation as long as the pH is about 5.2-6, but in physiological solutions with a pH value equal to a physiological pH of about 7-7.6, the risk of precipitation increases. Therefore, pH control is required not only during sterilization and storage, but also in the mixed and ready-to-use solutions. A problem is also that many of these fluids should remain stable for long periods of storage, up to 2 years.

In one of the above mentioned references, this problem is solved by using the composition as a powder for a solution, which is dissolved in a fluid prior to administration until the time of application. However, although attempts are made to maintain sterility according to the european pharmacopoeia in order to avoid the risk of infection of the patient, this is not the best way to maintain sterility. If the package breaks, for example by injecting the solution ingredients into a bag with the solution, and comes into contact with air, the solution is no longer a sterile solution. But a pathogen-free solution, nor can a pathogen-free solution be infused to a patient as such.

The best way is to terminally sterilize the solution in the package in order to ensure that the solution is as sterile as possible and also remains in such a sterile environment during mixing into a ready-to-use solution without the need to open the bag to contaminate the contents therein.

Summary of The Invention

It is an object of the present invention to provide a precipitate-free and sterile medical solution which ensures good stability during storage and use.

The present invention relates to medical solutions. The ready-to-use solution of the invention comprises phosphate in a concentration of 1.0-2.8mM, is sterile and has a pH of 6.5-7.6.

In one embodiment of the invention, the medical solution comprises phosphate in a concentration of 1.2-2.6mM and has a pH of 6.5-7.6 in its ready-for-use solution state.

In another embodiment, the medical solution, when in its ready-to-use solution state, comprises phosphate at a concentration of up to about 2.8mM and has a pH of 6.5-7.4.

In another embodiment, the medical solution, when in a ready-to-use solution state, comprises phosphate at a concentration of up to about 1.3mM and has a pH of 6.5-7.6.

In another embodiment, said medical solution is divided into at least two single solutions prior to use, wherein a first single solution comprises at least one buffer selected from the group consisting of acetate, lactate, citrate, pyruvate, carbonate and bicarbonate, and a second single solution comprises an acid, wherein said first and second single solutions are mixed into a ready-to-use solution after terminal sterilization and until use, and wherein said ready-to-use solution has a pH of 6.5-7.6.

In another embodiment, the second single solution has a pH of less than 2.5.

In another embodiment, the first single solution comprises bicarbonate and carbonate in proportions such that carbon dioxide, CO, in the first single solution₂Partial pressure and carbon dioxide C in atmosphereO₂The partial pressures are of the same order of magnitude and the second single solution has a pH of 1.0-1.5 and the ready-to-use solution has a pH of 7.0-7.6.

In an additional embodiment, the first single solution has a pH of 10.1 to 10.5, preferably 10.3.

In another embodiment, the second single solution has a pH of 1.3. In another embodiment, the second single solution comprises HCl.

In another embodiment, the first single solution includes phosphate ions.

In another embodiment, the second single solution includes phosphate ions. In another embodiment, the ready-to-use solution further comprises one or more electrolytes, wherein the one or more electrolytes comprise one or more of sodium, calcium, potassium, magnesium, and/or chloride ions. One or more electrolytes are formulated into the second single solution prior to mixing into a ready-to-use solution. In one embodiment, sodium ions and/or chloride ions are formulated into said first and said second single solutions prior to mixing into a ready-to-use solution.

In another embodiment, the first single solution comprises bicarbonate and carbonate, and the second single solution comprises calcium and/or magnesium.

In an additional embodiment, said first single solution comprises lactate and phosphate and said second single solution comprises calcium and/or magnesium.

In another embodiment, the second single solution further comprises glucose or a glucose-based compound.

The invention further relates to a method for the production method. The method of the present invention comprises providing said single solution in a separate chamber and thereafter terminally sterilizing said single solution.

The invention further relates to a multi-chamber bag comprising the method of the invention.

The invention also relates to the use of the method according to the invention.

Additional objects, features, advantages and preferred embodiments of the present invention will become apparent from the following detailed description when taken in conjunction with the appended patent claims.

Definition of

The term "medical solution" refers to dialysis solutions for hemodialysis, hemodiafiltration, hemofiltration and peritoneal dialysis, solutions for dialysis in renal intensive care, solutions for substitution or infusion, which usually contain buffer substances, and solutions for nutritional purposes.

The term "single solution" is used to refer to one solution that is kept separate from the other solution prior to use.

The term "bicarbonate and carbonate" is used to refer to alkaline bicarbonates and alkaline carbonates, especially sodium bicarbonate and sodium carbonate.

The term "ready-to-use solution" is intended to mean a solution that includes the different single solutions desired and is ready-to-use.

The term "multi-chamber bag" is used to refer to a bag that is divided into more than one chamber and the contents of the different chambers can be brought into contact with each other and mixed prior to use.

The term "terminal sterilization" is used to refer to the sterilization of a product in a final package. Terminal sterilization may include heat sterilization and/or radiation sterilization, but is preferably performed in an autoclave at a temperature of at least 100 ℃, preferably at least 121 ℃.

The term "as used" is intended to mean as close as possible to the time before the medical solution is used for its particular purpose.

The term "glucose or glucose-like compound" is used to refer to glucose; glucose polymers such as cellulose and starch; and other molecules containing at least one glucose unit, i.e., disaccharides, trisaccharides, and polysaccharides (glucans).

Brief Description of Drawings

FIGS. 1A-C are graphs showing the correlation between the pH in the final stock solution and the amount of particles produced 24 hours after mixing the solution containing 1.3mM phosphate solution.

FIGS. 2A-C are graphs showing the correlation between the pH in the final stock solution and the amount of particles produced 24 hours after mixing the solution containing 2.6mM phosphate solution.

Figures 3A-C are schematic diagrams showing the correlation between phosphate concentration and the amount of particles produced 24 hours after mixing a solution having a pH of 7.6.

Detailed Description

The present inventors have found that stable phosphate-containing sterile medical solutions can be provided in specific environments, concentrations, pH ranges and packaging processes, and that it forms the basis of the present invention.

One of the more important aspects of finding the most favourable environment, concentration, pH range and packaging is the formation of particles during production, storage and preparation of the ready-to-use solution. The amount of particles must be kept between the specified ranges for the particle size and amount of particles involved. This is specified in the european pharmacopoeia and for particles of 10 μm size the limit is 25 counts/ml. It is of utmost importance to keep particle formation to a minimum, otherwise the immune system may be triggered, possibly leading to the initiation of an inflammatory cascade. Another problem with the presence of particles is the risk of clogging the filters used during dialysis treatment.

The main component causing particle formation problems is the combination of calcium ions with carbonates and/or phosphates.

The problem which is considered to be the first to be urgently solved is that of keeping the calcium ions separated from the carbonate and phosphate during production and storage, which problem is still present when preparing the ready-to-use solution, whereby the formation of solid calcium carbonate and calcium phosphate may still occur during the mixing process.

The inventors have found that when the phosphate concentration in the ready-to-use solution is up to about 2.8mM, the amount of particles formed is within the allowable limits if the pH of the ready-to-use solution is kept at a value of at most 7.4, preferably at most 7.2.

When the phosphate concentration in the stock solution reaches approximately 1.3mM, the particles formed are within the permitted range if the pH of the stock solution is maintained at a value of at most 7.6, preferably at most 7.4.

The inventors have also found that calcium and phosphate can be kept together during preparation and storage, provided that the two components are kept in a chamber with a pH below 2.5, preferably below 1.5, and most preferably below or equal to 1.3.

In one embodiment of the invention the medical solution is divided into at least two single solutions before use, a first single solution and a second single solution, wherein said first and second solutions are mixed after terminal sterilisation and upon use to a final solution having a pH of 6.5-7.6.

The first solution includes at least one buffer selected from the group consisting of acetate, lactate, citrate, pyruvate, carbonate, and bicarbonate, and the second single solution includes an acid.

In another embodiment of the invention, the first single solution comprises bicarbonate and carbonate, in proportions such that the carbon dioxide CO in the first single solution is present₂Partial pressure and carbon dioxide CO in the atmosphere₂The partial pressures are of the same order of magnitude. The bicarbonate and carbonate salts are preferably mixed as sodium bicarbonate and sodium carbonate, and in one embodiment, the first single solution has a pH in the range of 10.1 to 10.5, preferably 10.3.

By adjustingCarbon dioxide CO in the first single solution₂Partial pressure and carbon dioxide CO in the atmosphere₂The partial pressures are of the same order of magnitude, and the carbon dioxide in the first single solution chamber remains in the bag chamber and does not escape from the bag material into the atmosphere because of the CO in the liquid₂Partial pressure and CO in air₂The partial pressures are kept in equilibrium.

In this embodiment, after mixing the first and second single solutions into a ready-to-use solution, the ready-to-use solution has a pH of 7.0 to 7.6. Furthermore, the ready-to-use solution preferably has a bicarbonate concentration of at least 25mM, preferably at least 30mM, and at most 45mM, preferably at most 40 mM.

However, as noted above, in another embodiment, the bicarbonate/carbonate combination in the first single solution may be exchanged or supplemented with one or more buffers selected from the group consisting of acetate, lactate, citrate, and pyruvate. In one embodiment, the buffer is bicarbonate at a concentration of 25-35mM, optionally with the addition of 0-15mM lactate, where the specified concentration is that in the ready-to-use solution.

In one embodiment, the second single solution preferably has a pH in the range of 1.0 to 1.5, most preferably a pH of 1.3. In one embodiment of the invention, the second single solution comprises HCl.

In one embodiment, the ready-to-use solution further comprises one or more electrolytes. The electrolyte is one or more of sodium, calcium, potassium, magnesium and/or chloride ions. The arrangement of the electrolytes in the different chambers depends on the common characteristics of the different electrolytes and other substances present in the single solution, i.e. whether some type of reaction can occur between one or more electrolytes and other substances present in a particular single solution. The electrolyte is typically contained in the second single solution. For example, it is preferred to have calcium and magnesium ions in any other single solution, but where the first single solution comprises a bicarbonate/carbonate combination, the first single solution comprises only bicarbonate and/or phosphate. The reason for this is that calcium and magnesium and bicarbonate/carbonate, bicarbonate and/or phosphate salts can generate calcium carbonate, magnesium carbonate, calcium phosphate and magnesium phosphate precipitates with each other. However, calcium and magnesium ions may in some cases coexist with bicarbonate, such as in a particular pH range, etc., as disclosed for example in EP 0437274, which is incorporated herein by reference. Furthermore, calcium and magnesium may also be present with the phosphate in some cases, see the above-mentioned literature.

On the other hand, sodium ions and/or chloride ions can generally be formulated into said first and said second single solutions.

The medical solution may further comprise glucose or a glucose-based compound, and in one embodiment, glucose or a glucose-based compound is formulated into the second single solution. During sterilization and storage, the glucose or glucose-like compounds should be kept at a low pH in order to ensure that the formation of Glucose Degradation Products (GDPs) is kept at a minimum. In one embodiment, the pH in the second single solution is less than 2.5.

In the method of producing a medical solution according to the above, the single solution is provided in a separate chamber. The single solution is then terminally sterilized. Preferably the terminal sterilisation is heat sterilisation and/or radiation sterilisation (see also the review of the european pharmacopoeia 1977 for different sterilisation techniques). In one embodiment of the process of the invention, the terminal sterilization is heat sterilization at a temperature of at least 100 ℃, preferably at least 121 ℃.

The sterilization time may vary depending on the sterilization temperature, the type of container, and the contents in which sterilization is desired.

The radiation sterilization may be ionizing or non-ionizing sterilization. Examples of ionizing sterilizations are gamma radiation and beta radiation. An example of non-ionizing sterilization is UV radiation.

The medical solution of the invention has the advantage of ensuring good stability and combined bioavailability.

The single solution may be provided in different chambers within the multi-chamber bag and mixing may be provided by uniting the different chambers with a frangible needle which can be broken to mix the contents of the different chambers within the multi-chamber bag. Further mixing may be provided by having a tearable sealing layer between the different chambers, which may be torn in order to mix the contents of the different chambers.

Examples

Different embodiments of the solution according to the invention can be found below.

Example 1

The following paired single solutions were prepared according to tables 1-5 below. The volume relationship between the first single solution and the second single solution is 1: 20.

TABLE 1 (solution 1)

Chloride ions as NaCl, CaCl₂、MgCl₂And HCl addition.

TABLE 2 (solution 2)

Chloride ions as NaCl, CaCl₂、MgCl₂And HCl addition.

TABLE 3 (solution 3)

Chloride ions as NaCl, CaCl₂、MgCl₂And HCl addition.

TABLE 4 (solution 4)

Chloride ions as NaCl, CaCl₂、MgCl₂And HCl addition.

TABLE 5 (solution 5)

Chloride ions as NaCl, CaCl₂、MgCl₂And HCl addition.

These solutions were sterilized in an autoclave at 121 ℃ for 40 minutes. After sterilization, the first and second solutions in each pair were mixed and the amount of particles of 2, 5 and 10 μm size were determined, respectively. The results are shown in table 6 below.

Particle counting was performed by means of a liquid particle counting system of the HIAC 9703 type (serial No. F08504) with Pharm, Spec.1, version 4 software.

As is evident from the results in table 6 above, the ready-to-use solutions obtained according to the present invention are well under the limits specified in the european pharmacopoeia.

Example 2

To find the optimal pH range for the ready-to-use solution in order to keep particle formation to a minimum level, a single solution pair in table 7 below was prepared and mixed. The volume relationship between the first single solution and the second single solution is 1: 20.

TABLE 7

Chloride ions as NaCl, CaCl₂、MgCl₂And HCl addition.

The mixed solution was divided into 2 portions, and 1.3mM NaH was added to 1 portion₂PO₄And adding 2.6mM NaH to the other portion₂PO₄.2 different solutions were poured into 50ml glass bottles and contained 2 different concentrations of NaH in each group₂PO₄The pH was adjusted to 6.8, 7.0, 7.2, 7.4, 7.6, 7.8, 8.0 and 8.2. The amount of particles was measured after 24 hours.

In FIGS. 1A-1C, the results from this assay were observed for solutions containing 1.3mM phosphate. In FIGS. 2A-2B, the results from this assay were observed for solutions containing 2.6mM phosphate.

As is evident from the figure, the pH of the ready-to-use solution with a phosphate concentration of 1.3mM should be lower than or equal to 7.6, preferably lower than or equal to 7.4. The pH of the stock solution at a phosphate concentration of 2.6mM should be less than or equal to 7.4, preferably less than or equal to 7.2. Particle formation of extremely small size is usually observed first, and then they aggregate and form larger particles. The upper pH limits selected to be 7.4 and 7.6, respectively, are based on particle property changes rather than absolute values. All measured particle sizes included in the evaluations with some exceptions were focused on the small particles before the larger particles were formed.

Example 3

To find the optimum upper limit for the phosphate concentration of the ready-to-use solution in order to keep particle formation to a minimum, a single solution pair in table 8 below was prepared. The volume relationship between the first single solution and the second single solution is 1: 20.

TABLE 8

Chloride ions as NaCl, CaCl₂、MgCl₂And HCl addition.

The first and second single solutions were mixed and divided into 5 different fractions, and phosphate was added at the following concentrations: 2.6, 2.8, 3.0, 3.5 and 4.0. The pH was adjusted to 7.6 and the amount of particles was measured 0 and 24 hours after mixing.

The results are shown in FIGS. 3A-C, from which it can be concluded that: the solution remains stable during 24 hours at phosphate concentrations less than or equal to 2.8mM phosphate and ph 7.6.

Thus, by bringing the phosphate concentration of the final ready-to-use solution having a pH of 6.5 to 7.6 to 1.0 to 2.8, a medical solution containing a stable phosphate can be provided.

Example 4

The following single solution pairs were prepared according to tables 9-11 and they constitute different embodiments of the present invention. The volume relationship between the first single solution and the second single solution in these solution pairs is 20: 1. Thus, at this point, the second single solution has a small volume and the first single solution has a larger volume.

TABLE 9

1) Sodium is taken as NaCl and NaHCO₃And Na₂HPO₄Adding the mixture.

2) Using chloride as NaCl, KCl and CaCl₂、MgCl₂And HCl was added.

3) Taking phosphate as Na₂HPO₄Added but after mixing the two single solutions it acts mainly as HPO₄ ^2-Are present. However, H₂PO₄ ^-And PO₃ ^3-And also exists due to the equilibrium between these ions. The concentration of each ion depends on the pH.

4) The amount of bicarbonate is excessive because some bicarbonate is converted to CO during mixing₂And thus out of solution.

Watch 10

1) Sodium is taken as NaCl and NaHCO₃、Na₂HPO₄And sodium lactate.

2) Chloride is used as NaCl and CaCl₂、MgCl₂And HCl was added.

3) Taking phosphate as Na₂HPO₄Added but after mixing the two single solutions it acts mainly as HPO₄ ^2-Are present. However, H₂PO₄ ^-And PO₃ ^3-And also exists due to the equilibrium between these ions. The concentration of each ion depends on the pH.

4) The amount of bicarbonate is overdosed because some bicarbonate is converted to CO during mixing₂And thus out of solution.

TABLE 11

1) Sodium is used as NaCl and Na₂HPO₄And sodium lactate.

2) Chloride is used as NaCl and CaCl₂、MgCl₂And HCl was added.

3) Taking phosphate as Na₂HPO₄Added but after mixing the two single solutions it acts mainly as HPO₄ ^2-Are present. However, H₂PO₄ ^-And PO₃ ^3-And also exists due to the equilibrium between these ions. The concentration of each ion depends on the pH.

Example 5

The following single solution pairs were prepared according to table 12 and constitute embodiments of the present invention. The volume relationship between the first single solution and the second single solution in the pair is 1: 20.

TABLE 12

1) Sodium is taken as NaCl and NaHCO₃、Na₂CO₃And Na₂HPO₄Adding the mixture.

2) Using chloride as NaCl, KCl and CaCl₂、MgCl₂And HCl was added.

3) Taking phosphate as Na₂HPO₄Added but after mixing the two single solutions it acts mainly as HPO₄ ^2-Are present. However, H₂PO₄ ^-And PO₃ ^3-And also exists due to the equilibrium between these ions. The concentration of each ion depends on the pH.

It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing its attendant advantages. Such changes and modifications are therefore to be considered as included in the appended claims.

Claims (16)

1. A method for producing a medical solution that is divided into at least two single solutions prior to use, the method comprising:

providing a first single solution comprising bicarbonate and phosphate in a separate compartment of a multi-compartment bag;

providing a second single solution comprising an acid and calcium and/or magnesium in another separate compartment of the multi-compartment bag;

terminally sterilizing the first and second single solutions within the multi-chamber bag; and when in use

Rupturing a frangible needle associated with the different chambers or tearing a seal between the different chambers and mixing the first and second solutions into a stock solution, wherein the stock solution comprises phosphate at a concentration of 1.0-2.8mM, is sterile and has a pH of 6.5-7.6.

2. The method of claim 1, wherein phosphate is included in the ready-to-use solution at a concentration of 1.2-2.6mM and has a pH of 6.5-7.6.

3. The method of claim 1, wherein phosphate is included in the ready-to-use solution at a concentration of up to about 2.8mM and has a pH of 6.5-7.4.

4. The method of claim 1, wherein phosphate is included in the ready-to-use solution at a concentration of up to about 1.3mM and has a pH of 6.5-7.6.

5. The method of any one of claims 1-4, wherein said second single solution has a pH of less than 2.5.

6. The method of any of claims 1-4, wherein the first single solution comprises bicarbonate and carbonate in proportions such that carbon dioxide, CO, in the first single solution₂Partial pressure and carbon dioxide CO in the atmosphere₂The partial pressures are of the same order of magnitude and the second single solution has a pH of 1.0-1.5, wherein the ready-to-use solution has a pH of 7.0-7.6.

7. The method of any one of claims 1-4, wherein said first single solution has a pH of 10.1-10.5.

8. The method of any one of claims 1-4, wherein said first single solution has a pH of 10.3.

9. The method of any one of claims 1-4, wherein said second single solution has a pH of 1.3.

10. The method of any one of claims 1-4, wherein the second single solution comprises HCl.

11. The method of any one of claims 1-4, wherein the stock solution further comprises one or more electrolytes.

12. The method of claim 11, wherein the one or more electrolytes comprise one or more of sodium, potassium, and/or chloride ions.

13. The method of claim 11, wherein one or more electrolytes are formulated into said second single solution prior to mixing into a ready-to-use solution.

14. The method of claim 12, wherein one or more electrolytes are formulated into said first and said second single solutions prior to mixing into a ready-to-use solution.

15. The method of any one of claims 1-4, wherein said second single solution further comprises glucose or a glucose-based compound.

16. Multi-chamber bag comprising a medical solution produced according to the method of any one of claims 1-15 having a first and a second single solution provided in different chambers.