Entitled standard solution filling body and use thereof

Technical field

[0001]

　The present invention, fillers filled with standard solution used to confirm that the bicarbonate-containing formulation used in preparing the dialysate and the dialysate during hemodialysis is used in the proper concentration to the container, as well as to the use of this standard solution packing.

Background technique

[0002]

　Hemodialysis (or dialysis therapy. Hereinafter abbreviated as "hemodialysis".) Is employed for chronic renal failure patients, etc., is artificially alternative treatment methods kidney function. In hemodialysis, it is transmitted through the dialyzer drawing the blood (dialyzer) of the body from the body, pull back into the body again. The dialyzer, through the dialysis membrane that is indirect contact with the dialysate blood, together with waste products in the blood are removed, electrolytes and water content in the blood is maintained. Per one time is hemodialysis, for example, dialysate 100-300 liters used.

[0003]

　Dialysate is usually prepared immediately before use. In a typical dialysis solution methods of preparation, and A agent and the B agent containing the bicarbonate (bicarbonate) containing an electrolyte component, after being mixed just prior to use, the dialysis water is replenished the concentration of each component is adjusted by. This is because some of the electrolyte components contained in the A agent may coexist with the main component is bicarbonate of B agent, they react with one another with time, causing an insoluble carbonate it is. Upon failure carbonates insoluble, with causing a precipitate in the dialysate, thereby changing the component concentration and the pH of the dialysate. Further, hydrogen carbonates contained in the dialysate is decomposed into over time carbon dioxide. Component concentration and pH of the dialysate by the decomposition reaction is changed.

[0004]

　Conventionally, as a method for avoiding the decomposition of the occurrence and bicarbonate ions of the insoluble carbonates, e.g., as disclosed in Patent Document 1 or 2, the A agent and the B agent, isolated by the partition method for accommodating respectively the multiple chambers is known. In this approach, the breakage of the partition wall at the site of use by mixing the A agent and the B agent, can be prepared dialysate just prior to use.

CITATION

Patent Literature

[0005]

Patent Document 1: JP-A-11-197240 Patent Publication
Patent Document 2: JP 2005-028108 JP

Summary of the Invention

Problems that the Invention is to Solve

[0006]

　As described above, it is prepared just before use dialysate, in other words, so that at any time prepared at the user site the required amount in the dialysate. Therefore, as compared dialysate on a large scale in a factory private facilities are provided such as to be prepared with quality control, variation is likely to occur in the concentration of the dialysate.

[0007]

　Here, in the method using a multi-chamber container as disclosed in Patent Document 1 or 2, it is possible to ship by filling the multi-chamber container prepared in advance A agent and B agent at the factory, dialysis it is possible to suppress variation in the concentration in the liquid. However, in this method, the amount of dialysate that is prepared is because it is limited to an amount that can accommodate A agent multiple chambers and B agent, for example, when dialysate or volume of the multiple chambers is required It can not be sufficiently respond to.

[0008]

　The present invention was made in order to solve such a problem, when any time preparing dialysate at the user site, without restriction in preparative amounts, possible to suppress variation in the concentration of the dialysate an object of the present invention is to provide a capable technique.

Means for Solving the Problems

[0009]

　Standard solution filling body according to the present disclosure, in order to solve the above problems, there filling body filled with the standard solution of bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container Te, the sealed container is formed of a material having a gas barrier property, the initial pH after filling in the standard solution is a configuration that is lower than the pH of the bicarbonate-containing formulation prepared target.

[0010]

　According to the configuration, when filling the bicarbonate-containing formulation used in the preparation of the dialysis fluid in a sealed container, it means that by lowering the initial pH in anticipation of increase in the pH of the filled standard solutions in advance. Thus, it is possible to avoid it is possible to maintain the pH of the standard solution even during storage in a suitable range, also insoluble salts are produced in accordance with the increase in pH standard solution. Therefore, since a long period of time it is possible to stably store the standard solution over, it is possible to appropriately adjust the concentration of the dialysis solution prepared at the user site. Accordingly, even when any time preparing dialysate at the user site, without restriction in preparative amounts, it is possible to suppress the variation of the concentration of the dialysate.

[0011]

　In a standard liquid filled body of the structure, said a bicarbonate-containing formulations dialysate, the standard solution is at least sodium ion, potassium ion, calcium ion, magnesium ion, bicarbonate and water, is set in advance that are those prepared by mixing in a mixing ratio, the initial pH after filling in the standard solutions may be configured to have become lower in 0.4 within than the pH of the dialysate preparation object .

[0012]

　According to the arrangement, and when bicarbonate-containing formulation is a dialysate reduced within 0.4 initial pH of the filled dialysate standard solution. Therefore, it is possible to avoid it is possible even during storage to maintain the pH of the dialysate standard solution within the preferred range, may be insoluble salt is produced in accordance with the pH increase of the dialysate standard solution . Thus, the dialysis standard solution for a long period of time because it is possible to stably store, it is possible to appropriately adjust the concentration of the dialysis solution prepared at the user site.

[0013]

　In the standard solution packing of the structure, the standard solutions, the acid component is a weak acid, and more monovalent or divalent metal ions including sodium ions, potassium ions, calcium ions, and magnesium ions containing the composition of the bicarbonate-containing formulation prepared subject when the reference, the content of the metal ion is equal to the reference, and the content of the acid component is greater than the reference composition it may be configured with.

[0014]

　According to the arrangement, it is set lower the pH by adjusting the content ratio of the weak acid and weak acid metal salts. At this time, without substantially changing the content of the metal ion, since the adjusting the content ratio of the weak acid and weak acid metal salts, while maintaining a substantial composition as a standard solution, setting a low pH be able to. Moreover, if it contains a weak acid metal salt as a source of metal ions may be weak acids behave as an acid pH buffering system, weak acid metal salt behaves as a conjugate base of a pH buffer system. Therefore, depending on the composition of the standard solution is not only to reduce the initial pH in advance anticipation increase of pH, pH of the filled standard solutions, it is possible to hardly increased by the pH buffering action.

[0015]

　In the standard solution packing of the structure, wherein the acid component is citric acid or acetic acid, wherein the metal ions of the conjugate base may be configured sodium ions.

[0016]

　Alternatively, in a standard solution packing of the arrangement, the said closed container, said are sealed gas filling of void space of the sealed container along with the standard liquid is filled, the filling gas is air or nitrogen gas consists of carbon dioxide, it may be configured carbon dioxide content of a mixed gas in the range of 3 to 20% by volume.

[0017]

　According to the arrangement, inside the filling body, at least, sodium ions, potassium ions, calcium ions, magnesium ions, and the standard solution prepared by mixing the bicarbonate and water, encapsulation of smaller volume than this gas is filled, the filler gas has a gas mixture containing in the range of 3 to 20% by volume of carbon dioxide. This makes it possible to substantially reduce the initial pH of the standard solution after filling. Therefore, even if the rising pH of the filled standard solution, it is possible to maintain within the preferred range, it is also possible to avoid the insoluble salts are produced in accordance with the increase in pH standard solution. Further, it is possible to fill gas is also effectively suppressed significant drop in pH which occurs when only carbon dioxide.

[0018]

　Therefore, if the standard solution packing of the structure, it is possible to stably store the standard solution for a long period of time. Therefore, when any time preparing dialysate at the user site is a standard solution of the standard solution filling body, by comparing the bicarbonate-containing formulations prepared, the concentration of bicarbonate-containing formulation prepared properly it can be adjusted to. As a result, even when from time to time preparing dialysate at the user site, without restriction in preparative amounts, it is possible to suppress the variation in the concentration of the dialysate.

[0019]

　In the standard solution packing of the configuration, the capacity of the sealed container is 100 vol%, the filling factor of the standard solution is in the range of 70 to 99 vol%, the filling factor of the filler gas there may be configured in the range of 1 to 30 vol%.

[0020]

　In the standard solution packing of the structure, the standard solution is the initial pH by the carbon dioxide is bubbled may be configured as one that is low.

[0021]

　In the standard solution packing of the structure, the standard solution is the initial pH by the acid is added may be configured as one that is low.

[0022]

　Another standard solution filling body according to the present disclosure, in order to solve the above problems, the filling bodies were filled with the standard solution of bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container a is, the sealed container is formed of a material having gas barrier properties, the standard solution until capacity limit of the closed container, or to the state not overflow beyond the capacity limit of the closed container, to the sealed container is a configuration that is filled.

[0023]

　According to the configuration, within the sealed container, substantially in a state where only the standard solution of bicarbonate-containing formulation are filled. Thus, it is possible to avoid the decomposition to carbon dioxide generation and bicarbonate insoluble carbonates in the standard solution, it is possible to maintain even the pH within a predetermined range after long-term storage. Therefore, it is possible to stably store the standard solution for a long period of time. Thus, when any time preparing dialysate at the user site is a standard solution of the standard solution filling body, by comparing the bicarbonate-containing formulations prepared, the concentration of bicarbonate-containing formulation prepared properly it can be adjusted to. As a result, even when from time to time preparing dialysate at the user site, without restriction in preparative amounts, it is possible to suppress the variation in the concentration of the dialysate.

[0024]

　In a standard liquid filled body of the structure, said a bicarbonate-containing formulations dialysate, the standard solution is at least sodium ion, potassium ion, calcium ion, magnesium ion, bicarbonate and water, is set in advance it may be configured in which was prepared by mixing in that the mixing ratio.

[0025]

　According to the configuration, within the sealed container, substantially at least, sodium ions, potassium ions, calcium ions, magnesium ions, only the dialysate standard solution is prepared by mixing the bicarbonate and water filled become that state. Thus, it is possible to avoid the decomposition to carbon dioxide generation and bicarbonate carbonates insoluble in dialysate standard solution, it is possible to maintain even the pH within a predetermined range after long-term storage. Therefore, it is possible to stably store the dialysate standard solution for a long period of time.

[0026]

　In a standard liquid filled body of the structure, when the total volume of the closed container to 100 vol%, so that the standard solutions filling rate is in the range of 80 to 100% by volume, filled into the sealed container it may be a configuration that is.

[0027]

　Further, in the above standard solution-filled member of any configuration, the standard solution of the bicarbonate-containing formulation, the A agent is sodium ion, potassium ion, an acidic aqueous solution containing calcium ions and magnesium ions, carbonate and B agent containing hydrogen salt, a standard solution of the dialysis solution prepared by mixing in a mixing ratio set and water, previously, or may be configured as a standard solution of the B agent.

[0028]

　Further, in the above standard solution-filled member of any configuration, the sealed container may be configured at least the body is made of glass.

[0029]

　Further, the present invention provides a dialysate preparation kit containing standard solution filling of any one of the configurations are also included.

[0030]

　Furthermore, the present invention provides method for producing a standard solution packing of the structure are also included. Specifically, the manufacturing method of the standard solution filling body according to the present disclosure, by filling a standard solution of bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container, the standard solution a method of manufacturing a packing body, the closed container is made of a material having a gas barrier property, the initial pH after filling in the standard solution, adjusted to lower than the pH of the dialysate preparation object it may be a configuration that.

[0031]

　In the production method of the standard solution packing of the structure, said a bicarbonate-containing formulations dialysate, the standard solution, at least, sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, was prepared by mixing at a preset the mixing ratio, the initial pH after filling in the standard solution, a configuration in which adjustment for reducing by 0.4 within than the pH of the dialysate preparation object it may be.

[0032]

　In the production method of the standard solution packing, the standard solutions, the acid component is a weak acid, sodium ions, potassium ions, calcium ions, and a plurality of kinds of monovalent or divalent metal ions including magnesium ion and those containing the composition of the bicarbonate-containing formulation prepared subject when the reference, the content of the metal ions equivalent to the reference, and the content of the acid component to more than the reference by adjusting the composition of the standard solution, it may be configured to adjust the initial pH.

[0033]

　In the production method of the standard solution packing, a filler gas filling of void space of the sealed container, so as to be smaller volume than the standard solution, by filling the sealed container with the standard solution, the initial pH was adjusted to the filler gas is composed of air or nitrogen gas and carbon dioxide, may be configured carbon dioxide content of a mixed gas in the range of 3 to 20% by volume.

[0034]

　In the method of manufacturing the standard solution packing of the structure, the standard solution by bubbling with carbon dioxide, may be configured to adjust the initial pH.

[0035]

　In the method of manufacturing the standard solution packing of the structure, by adding dilute hydrochloric acid to the standard solutions, it may be configured to adjust the initial pH.

[0036]

　Furthermore, another method for manufacturing a standard solution filling body according to the present disclosure, by filling a standard solution of bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container, the dialysate standard a method of manufacturing a liquid-filled body, overflowing the closed container is made of a material having gas barrier properties, the standard solution until capacity limit of the closed container, or exceeds the capacity limit of the sealed container until no state is configured to be filled to the sealed container.

[0037]

　In the production method of the standard solution packing of the structure, said a bicarbonate-containing formulations dialysate, the standard solution, at least, sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, it may be configured be prepared by mixing at a preset the mixing ratio.

[0038]

　In the above manufacturing method of the standard solution packing of any configuration, the a standard solution of the standard solution of bicarbonate containing formulations the dialysate, acidic containing sodium ions, potassium ions, calcium ions and magnesium ions and a agent is an aqueous solution, and B containing a bicarbonate, or to prepare a standard solution of the dialysate by mixing in a mixing ratio set and water, previously, or the containing bicarbonate the standard solution of the formulation may have a configuration which is a standard liquid of the B agent.

Effect of the invention

[0039]

　In the present invention, the above-described configuration, when any time preparing dialysate at the user site, the preparation amount without restriction, it is possible to provide a capable of suppressing the variation in the concentration of the dialysate technique , an effect that.

BRIEF DESCRIPTION OF THE DRAWINGS

[0040]

[1] be the result of an exemplary embodiment and a comparative example to which the standard solution filling body according to the present disclosure, a graph showing the results of temporal change in pH when stored at room temperature the standard solution packing it is.
A [2] Result of Comparative Example to Examples of standard liquid-filled body shown in FIG. 1 is a graph showing the results of temporal change in pH when stored at room temperature the standard solution packing.
[3] be the result of an exemplary embodiment and a comparative example to which the standard solution filling body according to the present disclosure, the temporal change in pH when stored standard solution packing in accelerated conditions of 40 ° C. is a graph showing the results.
A [4] The result of the comparative example with respect to an embodiment of the standard solution filling member shown in FIG. 3, a graph showing the results of temporal change in pH when stored standard solution packing in accelerated conditions of 40 ° C. it is.
[5] A result of an exemplary embodiment and a comparative example to which the other standard solution filling body according to the present disclosure, the results of the temporal change in pH when stored at room temperature the standard solution packing it is a graph showing.
A [6] results of Comparative Example to Examples of standard liquid-filled body shown in FIG. 5 is a graph showing the results of temporal change in pH when stored at room temperature the standard solution packing.
[7] be the result of a comparative example relative to Examples of other standard solution filling body according to the present disclosure, the results of the temporal change in pH when stored standard solution packing in accelerated conditions of 40 ° C. it is a graph showing.
[8] A result of an embodiment of another standard solution filling body according to the present disclosure, the results of the temporal change in pH when stored standard solution packing in accelerated conditions of storage at room temperature or 40 ° C. it is a graph showing.
[9] A result of an exemplary embodiment and a comparative example to which the other standard solution filling body according to the present disclosure, the results of the temporal change in pH when stored at room temperature the standard solution packing it is a graph showing.
[10] be the result of an exemplary embodiment of another standard solution filling body according to the present disclosure, it is a graph showing the results of temporal change in pH when stored at room temperature the standard solution packing.

DESCRIPTION OF THE INVENTION

[0041]

　Standard solution filling body and its manufacturing method according to the present disclosure, a filler packed with a standard solution of bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container, the sealed container It is composed of a material having a gas barrier property. In this disclosure, when any time preparing dialysate at the user site, the preparation amount without restriction, in order to suppress the variation of the concentration of the dialysate may be employed a plurality of configurations.

[0042]

　Exemplary configuration, the initial pH after filling in the standard solution, the configuration is lower than the pH of the bicarbonate-containing formulation prepared target or standard solution, to a volume limit of a closed container, or sealed to the state not overflow beyond the capacity limit of the container can include a configuration in which the sealed container is filled.

[0043]

　The former arrangement, more specifically, (1) standard solution and filler gas filling of void space of the sealed container is filled with, the filler gas is composed of air or nitrogen gas and carbon dioxide, structure content of carbon dioxide is a mixed gas in the range of 3-20% by volume, (2) multiple standard solutions, containing an acid component is a weak acid, sodium ions, potassium ions, calcium ions, and magnesium ions containing the seeds of the monovalent or divalent metal ions, the composition of bicarbonate-containing formulation prepared subject when the reference, the content of metal ions is equal to the reference, and the content of the acid component structure having the composition amount is more than the reference, (3) the standard solution, configuration in which the initial pH by the carbon dioxide is bubbled is low, (4) standard solution is acid added The initial pH can be cited a structure such as those which are low by being.

[0044]

　Here, as the bicarbonate-containing formulation of the present disclosure, containing bicarbonate (bicarbonate), as long as it is used in the preparation of the dialysate. Typically, mention may be made of the dialysis liquid itself. Alternatively, dialysate, and the A agent is an aqueous solution of acidic containing sodium ions, and B containing a bicarbonate salt, as long as it is prepared by mixing water, bicarbonate in this disclosure the content preparation, B agent is also included.

[0045]

　Hereinafter is a description of typical embodiments of the present disclosure, the following embodiments, a case is explained using the dialysate as bicarbonate-containing formulation. Of course, the present disclosure is not limited thereto, bicarbonate-containing formulations may be a B agent, it is needless to say that may be formulated for other dialysis.

[0046]

　(Embodiment 1)
　dialysate standard solution filling body according to the present embodiment, a packing filled with dialysate standard solution used in preparing the dialysis fluid for hemodialysis in a sealed container. Dialysate standard solution to be filled, at least sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, which was prepared by mixing in a mixing ratio set in advance, typically is sodium ion, and a agent is an aqueous solution of acidic containing potassium ions, calcium ions and magnesium ions, and B containing a bicarbonate (bicarbonate), mixing ratio set and water, previously in include those prepared by mixing. Further, the sealed container is formed of a material having a gas barrier property. Then, the sealed container, the dialysate and filler gas filling of void space of the sealed container is filled with the standard solution, the filler gas is composed of air or nitrogen gas and carbon dioxide, the carbon dioxide content of There is a gas mixture in the range of 3 to 20% by volume.

[0047]

　It will be specifically described below with an exemplary example of the present embodiment. In the following description, including the other embodiments as well the present embodiment, for convenience of explanation, the dialysate standard solution packing appropriately abbreviated as "standard solution packing" dialysate standard solution appropriately It shall be referred to as "standard solution".

[0048]

　[Dialysate standard solution]
　in a standard liquid filled body according to this embodiment, a standard liquid filled in the sealed container, suitable compositions (or appropriate electrolyte concentration and pH depending on the type of dialysate to be compared ) and it is prepared so. In the following description, a typical dialysate illustrating the configuration of the standard solution as an example.

[0049]

　In this embodiment, the general dialysate (i.e., a standard solution to be filled in the sealed container) as the A agent containing the electrolyte component and an acid component, and a B agent containing the bicarbonate, a predetermined amount It includes units of the two drugs mixed prepared by diluting by mixing the dialysis water. Incidentally mixing, process for preparing the dialysate, which is not limited to such a two-part mixing type, as described above, sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, is set in advance it may be one prepared by mixing a ratio.

[0050]

　Electrolyte components contained in the A agent is not particularly limited, is suitably selected depending on the type of dialysate, in general, for example, sodium ion, potassium ion, magnesium ion, monovalent, such as calcium ions or 2 valent metal ions; and the like can be given; chloride ions; citrate, lactate, gluconate ion, succinate ion, organic anions such as malate. Usually, the dialysate, among these electrolyte components, at least sodium ions, potassium ions, calcium ions, and magnesium because ions are included, the standard solution according to the present embodiment also includes these electrolyte components It is preferred.

[0051]

　Sodium ions contained in the standard solution, the sodium salt as a supply source in common. Specific sodium salt is not particularly limited, for example, sodium chloride, sodium acetate, sodium citrate, sodium lactate, sodium gluconate, sodium succinate, and sodium malate. It These sodium salt may be used only one kind, two kinds or more may be used in appropriate combination, but especially because sodium chloride is the most important salt is essential in vivo, as the sodium salt preferably is at least sodium chloride is used.

[0052]

　Potassium ions contained in the standard solution, the potassium salt as a supply source in common. Specific potassium salt is not particularly limited, for example, potassium chloride, potassium acetate, potassium lactate, potassium citrate, potassium gluconate, potassium succinate, be mentioned potassium malate. Because to these potassium salt may be used only one kind, two kinds or more may be used in appropriate combination, but especially potassium chloride is positioned as particularly important salts like the sodium chloride in the body, it is preferable that at least potassium chloride is used as the potassium salt.

[0053]

　Magnesium ions contained in the standard solution, the magnesium salt as a supply source in common. Specific magnesium salt is not particularly limited, examples thereof include magnesium chloride, magnesium acetate, magnesium lactate, magnesium citrate, magnesium gluconate, magnesium succinate, magnesium malate. It These magnesium salts can be used only one kind may be used in combination of two or more as appropriate. These magnesium salts can be used in the form of a hydrate. Representative magnesium salts, and magnesium chloride.

[0054]

　Calcium ions contained in the standard solution, the calcium salt as a supply source in common. Specific calcium salt is not particularly limited, examples thereof include calcium chloride, calcium acetate, calcium lactate, calcium gluconate, calcium succinate, calcium malate. It These calcium salts may be used only one kind may be used in combination of two or more as appropriate. These calcium salts can be used in the form of a hydrate. Representative calcium salts, and calcium chloride.

[0055]

　Chloride ions contained in the standard solution, the chloride salt is the source generally. Specific chloride salt is not particularly limited, chloride salts of monovalent or divalent metal ions mentioned above, i.e. sodium chloride, potassium chloride, magnesium chloride, and calcium chloride. Chloride salts of these metal ions, as well as chloride ions, sodium ions, potassium ions, magnesium ions, and so can be a source of calcium ions is preferably used. Incidentally, the these chloride salts may be used only one kind, two kinds or more may be used in combination. Furthermore, when using hydrochloric acid as the acid component contained in the standard solution, the hydrochloric acid may also be the source of chloride ions.

[0056]

　There is no particular limitation on the organic acid ion contained in the standard solution, like the chloride ion, typically salts of the organic acid is a source. Furthermore, when using each organic acid as the acid component contained in the standard solution, also these organic acids may be the source of the organic acid ion.

[0057]

　Specific content of the electrolyte components contained in the standard solution is not particularly limited, it can be appropriately set according to various conditions. Incidentally, among the electrolyte components as described above, the content of sodium chloride is usually set to the maximum in comparison with the other electrolyte components each content. This is because the content of sodium chloride is set in accordance with the concentration of electrolytes in the blood. The dialysate prepared concrete content of sodium chloride in the (standard solution is filled) (concentration), for example, based on the sodium ion content in the range of 75mEq / L ~ 150mEq / L, preferably it can be mentioned within the scope of the 80mEq / L ~ 145mEq / L.

[0058]

　Therefore, during A agent, sodium ion content in the standard solution has only to contain sodium sources such as sodium chloride to be within the scope of the. Similarly, for the electrolyte component other than sodium ion, it is sufficient to contain a source of the ions in the A agent to a desired range in the standard solution.

[0059]

　The acid component contained in the A agent, may be a general organic or inorganic acid preferably in the field of dialysis fluid. Specifically, examples thereof include acetic acid, citric acid, lactic acid, hydrochloric acid or the like. These acid components may may be anhydrous be hydrates. Representative acid components, mention may be made of acetic acid or citric acid. Also, it may be added are salts of acid component having a buffer action for the purpose of stabilizing the pH. Representative salts include sodium acetate, sodium citrate.

[0060]

　Specific content of the acid component contained in the standard solution is not particularly limited, it can be appropriately set according to various conditions. For example, when the acid component is acetic acid, based on the acetate ion in the range of 2mEq / L ~ 6mEq / L, but preferably it may be mentioned the range of 3mEq / L ~ 5mEq / L, particularly limited not. Also, when the acid component is citric acid, based on the citric acid ion, within the range of 1.5mEq / L ~ 5mEq / L, preferably may be mentioned the range of 2mEq / L ~ 3mEq / L .

[0061]

　If the acid component is only to be contained within a suitable range, it is possible to adjust the pH of the standard solution within the preferred range. For example, when the acid component is acetic acid (in the case of standard solution containing acetic acid) is in the range of pH 6.5 to 8.0, preferably adjusted to the range of 7.1-7.4 be able to. Also, when the acid component is citric acid (for a standard solution containing citric acid) is in the range of pH 7.0 to 8.5, preferably in the range of 7.5-8.0 it can be adjusted. Therefore, during A agent, they need only contain an acid component to fall within a suitable range as described above with a standard solution.

[0062]

　The A agent, may contain components other than the electrolyte component and the acid component described above. In other words, the dialysate is prepared (standard liquid to be filled) can in addition to the electrolyte component and the acid component, contain a variety of components to be acceptable as a component of the dialysate. Specific other constituents, such as glucose (dextrose), pH adjusting agents and the like.

[0063]

　Glucose may be added to the dialysate in order to maintain the blood glucose level of the hemodialysis subjects. Specific content of glucose (concentration) is not particularly limited, it can be appropriately set according to various conditions. Representative The content of glucose, for example, in the range of 0 ~ 2.5 g / L in dialysate prepared (standard liquid to be filled), preferably in the range of 1.0 ~ 2.0 g / L it can be mentioned. Therefore, during A agent, they need only contain glucose to fall within a suitable range as described above with a standard solution.

[0064]

　pH adjusting agent, for the purpose of adjusting the pH of the standard solution, can be added separately from the acid component contained in the A agent. In other words, standard solutions, for the purpose of assisting the pH adjusting function of the standard solution with an acid component may contain a separate pH adjusting agent and acid components. Specific pH adjusting agents, such as citric acid, oxalic acid, tartaric acid, maleic acid, ascorbic acid, oxaloacetic acid, gluconic acid, and the like isocitrate, organic acids such as malic acid, and pyruvate. These organic acids may be used only one kind may be used in combination of two or more as appropriate. Further, these organic acids include sodium salts, potassium salts, may be used as a salt such as magnesium salt.

[0065]

　Specific content of the pH adjusting agent (concentration) is not particularly limited. pH adjusting agent can adjust the pH of the dialysate (standard solution to be filled) prepared within the preferred range, and the degree that does not adversely affect the function of the electrolyte component and the acid component described above (or their the amount of the functional components extent not interfere) need be added. Thus, even during the A agent, it is possible to adjust the pH of the standard solution, so that the amount that does not affect the function of the electrolyte component and the acid component, pH modifiers only to be contained.

[0066]

　The bicarbonate (bicarbonate) contained in the B agent, and sodium bicarbonate (sodium bicarbonate). May be used bicarbonate salt other than sodium bicarbonate, but is preferably the bicarbonate contained in the B agent is sodium bicarbonate only. Specific content of the bicarbonate is not particularly limited, it can be appropriately set according to various conditions. In general, in the range of 15mEq / L ~ 45mEq / L in dialysate prepared (standard liquid to be filled), it can preferably be mentioned within the scope of 25mEq / L ~ 40mEq / L.

[0067]

　B agent may be composed with bicarbonate of at least such sodium bicarbonate but may contain other components. Other components may include for example, sodium chloride, and the like. The content of the other components is not particularly limited, it can be appropriately set according to various conditions. Thus, during the agent B, it is sufficient that the other ingredients are added to the extent that does not affect the function of the bicarbonate.

[0068]

　Aforementioned A include, but are formulated as acidic liquid containing at least an electrolyte component and an acid component described above (aqueous), B agent may be formulated as a solid (e.g., powder) as a liquid (aqueous solution) it may be formulated. Even if B agent is a liquid, the concentration of bicarbonate is not particularly limited. When bicarbonate salts contained in the B agent is sodium bicarbonate, for example, in the range of 40 ~ 80 g / L, preferably may be mentioned the range of 60 ~ 80g / L.

[0069]

　The standard solution filling body according to this embodiment, a standard liquid filled in the sealed container is preferably prepared by diluting the dialysis water by mixing the A agent and the B agent described above. In other words, the standard solution only needs to be filled in a sealed container on which is prepared similarly to dialysate is actually prepared. For example, as in the examples described later, if the acid component is citric acid, pH of a typical dialysate, typically in the range 7.4 to 8.0. Therefore, pH of the standard solution is also only to be adjusted within this range. Specific preparation methods of standard solutions containing also adjustment of pH is not particularly limited, and may be the same as a process for the preparation of a typical dialysate.

[0070]

　[Closed container]
　In the standard solution filling body according to the present embodiment, the specific type of closed container filled with a standard solution described above is not particularly limited. The sealed container as long as it has a sealing property and gas barrier property enough to stably hold the filled standards and later enclosed gas can be suitably used a known container.

[0071]

　Typical closed container, can be mentioned glass container at least the container body is made of glass. Specific glass containers can include vials, ampoules, cartridges and the like. While the dialysate has to be prepared in quantity, standard solutions as a reference for the preparation of the dialysate so good in a small volume, preferably a glass container having a small capacity used for injection as such vials or ampoules be able to. Depending on the operating conditions of the standard solution, it is also possible to use a syringe as the glass container.

[0072]

　If the closed container is a vial or the like, the plug member is used to seal sealing the opening. Specific plug member is not particularly limited, without substantially affecting against a standard solution, and which can be suitably hermetic seal an opening of the vial, etc., preferably a known plug member it can be used. When the sealed container is a vial, as the plug member can be suitably used known rubber plug, a silicone plug, a cork or the like. Further, in order to improve the reliability of the hermetic seal, can be used in combination aluminum or alloy cap it.

[0073]

　As the sealed container, known resin container than glass containers (resin container) it can also be suitably used. Such resin container may be one in which the container body is formed by a hard resin material, or may be formed of a resin material softer having flexibility or flexibility. If the closed container is ones having an opening so that the vial described above with a resin container may be a known plug member for sealing sealing the opening like the vial.

[0074]

　Capacity of the sealed container is not particularly limited. Standard solutions, in preparing the dialysate, the amount enough to check the concentration of the electrolyte component contained in the dialysate, the acid component, and bicarbonate (as well as other components) is required. Therefore, the capacity of the sealed container may have a volume more than volume of the standard solution required for concentration check of each component. The standard solution filling body according to the present embodiment, as described below, will be added a filler gas also filled in the standard solution, the volume of the filler gas is less than the volume of the standard solution (less volume than standard solution) . Therefore, the capacity of the sealed container may have a capacity in consideration of the filling amount of the filler gas in addition to the necessary amount of standard solution.

[0075]

　[Dialysate standard solution filling]
　standard solution filling body according to the present embodiment, at least sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, mixed in a mixing ratio set in advance prepared by (as described above, a preferable example, by mixing the a agent and the B agent is diluted with dialysis water) the standard solution was prepared by, for hermetic seal by filling the standard solution in a sealed container be (production). In this case, the sealed container, in addition to the standard solution, a filler gas smaller volume than the volume of the standard solution is filled.

[0076]

　Filler gas to be filled in a sealed container, which may be a mixed gas of air or nitrogen and carbon dioxide (carbonic acid gas), the content of carbon dioxide in the mixed gas, the upper limit is less than 20 vol% It has become. Thus, it is possible to effectively suppress the volatilization of the bicarbonate from the standard solution, it is also possible to suppress temporal increase in pH. Moreover, since the content of carbon dioxide in the sealed gas is not excessive, it can also be effectively suppressed significant lowering of the pH resulting from penetration of carbon dioxide.

[0077]

　When the content of carbon dioxide is more than 20% by volume, carbon dioxide is excessively dissolved into a standard solution, the standard solution pH is lower preferable values ​​of the standard solution in the filling body (e.g., if the acid component is citric acid component 7. 4) there is a risk that less than. If the pH of the standard solution is lower than the predetermined range, the concentration of each component of the standard solution deviates from the predetermined range, as a result, can not be used as a standard solution. The lower limit of the content of carbon dioxide in the gas mixture may be at 3% by volume or more. When the content of carbon dioxide is less than 3 vol%, pH of the standard solution is preferable upper limit in the standard solution filling body (e.g., acid component 8.0 if citric acid component) which may exceed. If the pH of the standard solution exceeds a predetermined range, in the same manner as in the reduction of the pH, the concentration of each component of the standard solution deviates from the predetermined range, as a result, can not be used as a standard solution.

[0078]

　In a standard liquid filled body, it suffices sealed gas-filled so as to satisfy the void portion in the closed container, but the filling factor in the closed container of the filling gas (volume to be filled) is less than the filling factor of the standard solution it is preferable. Specifically, the volume of the closed container is 100 vol%, the filling factor of the standard solution may be not less than 50% by volume, preferably in the range of 70 to 99 vol%, 80-95 vol% range can be cited more preferably. Accordingly, the filling rate of the filler gas may be less than 50% by volume, preferably in the range of 1 to 30 vol%, more preferably in the range of 5-20% by volume. If the filling rate of the filler gas is larger than the filling rate of the standard solution, carbon dioxide in the fill gas is excessively dissolved into a standard solution, pH of the standard solution is likely to fall below the preferred lower limit value in the standard solution filling body.

[0079]

　Method of filling standards and filling gas into the sealed container is not particularly limited, it may be suitably used methods known in the art of dialysate or drug packaging. Process for the preparation of mixed gas is sealed gas is not particularly limited, may be suitably used a known method. Also, filling the standards and the filler gas in a sealed container, a method of hermetic seal is not particularly limited, may be suitably used a known method.

[0080]

　Standard solution filling of use]
　standard solution filling body according to the present embodiment, when preparing the dialysis fluid in the dialysis field, can be used when checking the components contained in the dialysate. Specifically, for example, dialysis situ diluted with dialysis water by mixing the A agent and the B agent dialysate was prepared by sampling the dialysate to measure the concentration of the electrolyte component. Furthermore, by sampling the standard solution by opening the standard solution packing measuring the concentration of the electrolyte component. Comparing the concentration of the electrolyte component of the concentration of the electrolyte component of the dialysate and the standard solution, or these concentrations which substantially coincides with, or the concentration of the electrolyte component of the dialysate compared to the concentration of the electrolyte component of the standard solution determines whether or not is within the allowable range Te.

[0081]

　Or another concentration is substantially equal to, the concentration of the electrolyte component of the dialysate if within the allowable range, the dialysate is that they are prepared at a concentration of suitable electrolyte components. On the other hand, have different concentration each other, if it is outside from the allowable range, the concentration of the electrolyte component of the dialysate was adjusted appropriately, repeated concentration compared between dialysate and standard solution. Method of measuring the concentration of the electrolyte component used at this time is not particularly limited, may be used commercially available measuring device or a known measuring methods, and the like. Further, in the standard solution filling body, the pH of the standard solution is maintained within a predetermined range, it is also possible to compare the pH of the pH and the standard solution prepared dialysate. Measurement method of pH used at this time is not particularly limited, may be used a method for measuring such commercial pH measuring device or pH.

[0082]

　Standard solution filling body according to the present embodiment can be stored in a predetermined storage time at room temperature. As shown in the examples below, the standard liquid filling body according to the present embodiment can be stored for at least 2 weeks at room temperature. Further, as shown in the examples below, it is possible to maintain the pH be stored for two weeks at 40 ° C. accelerated conditions within a predetermined range, standard solution filling body according to the present embodiment is about 1 month it is also possible to save. Further, by setting the storage conditions appropriate, it is also possible to store about one year. Incidentally, at room temperature here is, room temperature defined by JIS (20 ± 15 ℃, 5 ~ 35 ℃) may be within the range of.

[0083]

　Standard solution filling body according to the present embodiment, as described above, but can be suitably used in the preparation of the dialysate, usage of standard solution filling member is not limited only to the preparation of the dialysis fluid, for example, it can be used as one component of the dialysate preparation kit. Accordingly, with the present embodiment, the dialysis solution preparation kit containing standard solution packing, or also include evaluation kit for evaluating the quality of the dialysate. Preparation kit or evaluation kit dialysate only needs comprise at least a standard solution packing described above, there is no particular limitation on other elements constituting these kits.

[0084]

　For example, if the preparation kit of the dialysate may be a kit the A agent and the B agent described above with a standard solution packing. Alternatively, if the evaluation kit dialysate instrument with standard solution packing, instruments for sampling the dialysate, the instrument used to measure the concentration of the electrolyte component (or measuring instrument) used for the measurement of pH ( or it may be a kit of the measurement equipment), and the like.

[0085]

　Furthermore, with the present embodiment, a manufacturing method (manufacturing method) of the standard solution fillers described above are also included. For example, a method for producing a standard solution filling body according to the present embodiment, by filling the standard solution of the dialysis solution used in preparing the dialysis fluid for hemodialysis in a sealed container, the dialysate standard solution a method of manufacturing a packing, the standard solution, at least, sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, was prepared by mixing in a mixing ratio set in advance, sealed container is made of a material having a gas barrier property, a filler gas filling of void space portion in the closed container, so that a smaller volume than the standard solution, was charged in a sealed container together with the standard solution, encapsulated gas, air or It consists of nitrogen gas and carbon dioxide, carbon dioxide content of a mixed gas in the range of 3-20% by volume, that can be mentioned configuration.

[0086]

　In the method of manufacturing such a standard solution fillers, standard solutions, containing as mentioned above, the A agent is an aqueous solution of acidic containing sodium ions, potassium ions, calcium ions and magnesium ions, bicarbonate and B agent, can be prepared by mixing in a mixing ratio set with water in advance.

[0087]

　As described above, in the present embodiment has illustrated the dialysate as bicarbonate-containing formulation to be filled into the sealed container, the present disclosure is not limited thereto, bicarbonate-containing formulation, bicarbonate (carbonate containing hydrogen salt), it may be those used in the preparation of the dialysate. Therefore, also in this embodiment, to B agent may be filled in a sealed container as bicarbonate-containing formulation, other bicarbonate-containing formulation may be filled into the sealed container.

[0088]

　(Embodiment 2)
　dialysate standard solution filling body according to the present embodiment, similarly to the first embodiment, the dialysate standard solution sealed container used in preparing the dialysis fluid for hemodialysis a filling material filled in. Dialysate standard solution to be filled, at least, those of sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate (bicarbonate) and water, was prepared by mixing in a mixing ratio set in advance There, typically sodium ion, potassium ion, and a agent is an aqueous solution of acidic containing calcium ions and magnesium ions, and B containing a bicarbonate (bicarbonate), and water, previously It includes those prepared by mixing in a mixing ratio set. Further, the sealed container is formed of a material having a gas barrier property. Standard solution until capacity limit of a closed container, or to the state not overflow beyond the capacity limit of the sealed container is filled to the sealed container.

[0089]

　It will be specifically described below with an exemplary example of the present embodiment. The standard solution used in the standard solution filling body according to the present embodiment, since the the same as those described in the first embodiment, in the present embodiment is omitted a detailed description of the standard solution.

[0090]

　Further, a specific configuration of a closed container used in the standard solution filling body according to the present embodiment is not particularly limited, a closed container as described in the first embodiment can be suitably used. That is, the closed container, as long as it has a sealing property and gas barrier property enough to stably hold the filled standard solution, can be preferably used known containers. Therefore, also omitted specific explanation of the sealed container in this embodiment. In the standard solution filling body according to the present embodiment, as described later, as the sealed container is substantially filled with the standard solution, the standard solution is filled. Therefore, the capacity of the sealed container may have a capacity obtained by adding the reserve amount that can be predicted in the necessary amount of standard solution.

[0091]

　[Dialysate standard solution filling]
　standard solution filling body according to the present embodiment, at least sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, mixed in a mixing ratio set in advance prepared by (as described above, a preferable example, by mixing the a agent and the B agent is diluted with dialysis water) the standard solution was prepared by, for hermetic seal by filling the standard solution in a sealed container be (production). In this case, standard solution until capacity limit of a closed container, or to the state not overflow beyond the capacity limit of the sealed container is filled to the sealed container. Thus, within the sealed container, to become a state in which only substantially dialysate standard solution is filled, the inside of the sealed container be substantial gap portion is generated is suppressed. If substantially avoid the generation of air gap, bicarbonate of standard solution is decomposed into carbon dioxide, it is possible to substantially avoid being released into the gap portion, the temporal increase in the pH of the standard solution it can be suppressed.

[0092]

　In a standard liquid filled body, when the total volume of the closed container 100 vol%, as is ideally filling rate is in the range of 100 vol%, that standard solution is filled in a sealed container preferable. However, the shape of the sealed container, the method of hermetic seal, the filling method or the like in accordance with a closed container, if the filling rate of the standard solution in a closed container to be difficult to fill such that 100% by volume (or it may not be necessary to fill) such that 100% by volume. Therefore, in this embodiment, may be filled with the standard solution in a sealed container as the lower limit of the filling rate of the standard solution is 80 vol% or more, to fill the standard solution such that 90% or more by volume preferably, it is more preferable to fill the standard solution such that 95% by volume or more.

[0093]

　For example, in the Examples and Comparative Examples described later, using a glass vial as a closed container. The container body of a typical vial is a cylindrical shape having substantially the same inner diameter from the container bottom up to the top, the top of the container, the shoulder than the container body narrowed inner diameter is formed, a shoulder the upper end of the section is provided with an opening which is hermetically sealed with a plug member. When using the vial as the sealed container, the standard solution, in addition to the inner space of the cylindrical container body from the shoulder to the opening but the interior space also it is preferable to fill the standard solution, including shoulder it may not be filled to satisfy the standard solution for the interior space.

[0094]

　As described above, the inner diameter of the shoulder portion is smaller than the container body, also, the height of the shoulder is much smaller than the height of the container body. Therefore, the capacity of the shoulder portion, sufficiently smaller than the capacity of the container body, it is possible that the capacity of the shoulder portion when viewed from the entire volume of the closed container can be regarded as an error range. Further, in the state of being filled with the standard solution to the container body, even in the shoulder it has been a void portion, the standard solution is in a state facing the air gap of a very small volume in a very small area. Therefore, the release of carbon dioxide from the standard solution for the gap portion (generated by bicarbonate is decomposed) can be regarded as not substantially occur.

[0095]

　In other words, in a vial, will be a state in which meet at least the container main body has reached a capacity limit, the inner space of the shoulder is a space outside the capacity limit of the vial, it can be said that. Therefore, if the sealed container is a vial, as long as it extends the standard solution in a part of the shoulder portion fulfills the container body, not overflow beyond the capacity limit of the vial (sealed container) (internal space of the container body) thus filled with the standard solution to the state. Furthermore, it is also possible to fill the standard solution to fill the interior space of the shoulder. In this case, the packed standard solution to the vial (substantial total volume of the closed container) capacity limit of (sealed container).

[0096]

　As the sealed container, as described above, it is also possible to use a glass ampoule. General ampoule has a cylindrical container body similar to the vial, located on top of the container body, and a head tip greatly inner diameter smaller than the container body is sealed melted sealing (neck) . Since the head (neck) is to be folded, in use, a cylindrical container body constitutes the entire volume of the substantially sealed container.

[0097]

　In other words, also in ampules, will be a state filled container body reaches the capacity limit, the inner space of the head (neck) is a space that deviates from the capacity limitations of the ampoule, it can be said that. Therefore, if the sealed container is an ampoule, if span is standard solution in a part of the head (neck) fulfills the container body, reference solution to the state not overflow beyond the capacity limit of the ampule (sealed container) It will be filled with. Furthermore, to the extent that not the tip of the head to interfere melting sealing, it is also possible to fill the standard solution to the limit. In this case, the filled with the standard solution to a volume limit of the ampule (sealed container).

[0098]

　Incidentally, the sealed container is, as such vials or ampoules mentioned above, configured out with "body portion" of the container "small volume portion" such as shoulder or head (the portion inside the capacity is less than the body portion) is if they will be, when the capacity of only a main portion is 100 vol% (the maximum capacity of the sealed container will exceed 100% by volume), 100% by volume filling ratio of the standard solution in the body portion preferably it is over. In this case, standard solutions will be up to a small volume portion of such shoulder or head exceeds the capacity limit of the body portion. Therefore, it is possible to sufficiently reduce the volume of the void portion remaining inside the small-capacity portion.

[0099]

　In this embodiment, a method of filling a standard solution in a sealed container is not particularly limited, may be suitably used methods known in the art of dialysate or drug packaging. Further, by filling the standard solution in a sealed container, a method of hermetic seal is not particularly limited, may be suitably used a known method.

[0100]

　Since even the use of standard solution filling body according to the present embodiment is the same as that of the first embodiment, it is omitted specific explanation of its use. Here, in this embodiment, similarly to the first embodiment, the manufacturing method (manufacturing method) of the standard solution fillers described above are also included. For example, a method for producing a standard solution filling body according to the present embodiment, by filling the standard solution of the dialysis solution used in preparing the dialysis fluid for hemodialysis in a sealed container, the dialysate standard solution a method of manufacturing a packing, the standard solution, at least, sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, was prepared by mixing in a mixing ratio set in advance, sealed container is made of a material having a gas barrier property, standard solution until capacity limit of a closed container, or to the state not overflow beyond the capacity limit of the closed container is filled into the sealed container, given the structure of be able to.

[0101]

　Further, as described above, also in the second embodiment, similarly to the first embodiment has exemplified the dialysate as bicarbonate-containing formulation to be filled into the sealed container, the present disclosure is not limited thereto, heavy carbonate-containing formulation contains bicarbonate (bicarbonate), as long as it is used in the preparation of the dialysate. Therefore, also in the second embodiment, to B agent may be filled in a sealed container as bicarbonate-containing formulation, other bicarbonate-containing formulation may be filled into the sealed container.

[0102]

　(Embodiment 3)
　dialysate standard solution filling body according to the present embodiment, as in Embodiment 1 or 2 of the embodiment, sealing the dialysate standard solution used in preparing the dialysis fluid for hemodialysis a packing filled into the container. Dialysate standard solution to be filled, at least sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, which was prepared by mixing in a mixing ratio set in advance, typically is sodium ion, and a agent is an aqueous solution of acidic containing potassium ions, calcium ions and magnesium ions, and B containing a bicarbonate (bicarbonate), mixing ratio set and water, previously in include those prepared by mixing. Further, the sealed container is formed of a material having a gas barrier property. Then, the initial pH after filling in the dialysate standard solution is lower by 0.4 than than the pH of the dialysate preparation object (reference pH).

[0103]

　It will be specifically described below with an exemplary example of the present embodiment. The standard solution used in the standard solution filling body according to the present embodiment, the sealed container, filling method, for use or the like of the filling material, since the identical or common to those described in Embodiment 1 or 2 omitted these specific explanation in the present embodiment.

[0104]

　By "initial pH" in the present embodiment, it refers to the pH of the period from immediately after filling the standard solution in a sealed container until 1 day. Although not particularly limited approach set low at less than 0.4 than the reference pH initial pH of the standard solution, typically (1) to the standard solution, and a weak acid, the supply of the monovalent or divalent metal ions when containing the same and a weak acid metal salt which is the source, based on the content of the dialysate preparation object, the content of metal ions is equal to the reference, and the content of the acid component so that more than the reference, a technique for adjusting the content of weak acid metal salts, (2) method of the standard solution is bubbled with carbon dioxide, may be mentioned a technique such as the addition of acid (3) trace.

[0105]

　First, a description will be given of the method (1). As described in the first embodiment, typical dialysate, and with two drugs mixed type A agent and the B agent, the A agent and contains an electrolyte component and an acid component. As the acid component, as described above, it can be used acetic acid, citric acid, lactic acid, hydrochloric acid, the electrolyte component, more monovalent or divalent comprising sodium ions, potassium ions, calcium ions, and magnesium ions included is a metal ion. As the source of these metal ions may be used acetic acid salts of these metal ions, citrate, lactate, chloride or the like.

[0106]

　Therefore, based on the composition of the dialysate preparation object, the content of metal ions is equal to the reference, and the content of the acid component to be larger than the reference, adjusting the composition of the standard solution. Specifically, for example, as a source of metal ions, if weak acid metal salt is used is the acid component, a metal salt of the weak acid is a factor of increasing the pH of the standard solution. Therefore, with increasing content of weak acids reduces the weak acid metal salts, furthermore, by increasing the other amount of the source of metal ions, such that the content of metal ions is maintained equal to the reference adjust.

[0107]

　In other words more specifically, in the method of (1), the composition of the dialysate preparation object when the reference composition, the content of metal ions in the composition of the standard solution, compared to the amount of standard composition a range regarded as substantially equivalent, the content of the acid component in the composition of the standard solution is adjusted to be larger as compared with the content of the reference composition.

[0108]

　For example, in Example 7 or 8 described later, the anhydrous citric acid is used as acid component of the A agent, as a source of sodium ions, sodium citrate (dihydrate) and sodium chloride is used. Therefore, by increasing the content of anhydrous citric acid, together with reducing the content of sodium citrate, the content of sodium ions to the reference substantially equivalent to, increase the content of sodium chloride, which Accordingly, the initial pH of the standard solution can be reduced within 0.4.

[0109]

　Here, when viewed as a component of the standard solution, weak acid behaves as an acid in a pH buffer system, it is possible to either one metal ion behaves as conjugate base of a pH buffer system. In Example 7, citric acid anhydrous, behave as weak acid pH buffer system, sodium hydrate citric acid, may behave as a conjugate base of a pH buffer system. Therefore, not only to reduce the initial pH in advance anticipation increase in pH, the pH of the dialysate standard solution, it is possible to hardly increased by the pH buffering action.

[0110]

　The specific types of weak acid is not particularly limited, other than citric acid exemplified in the Examples may be used acetic acid or lactic acid and the like described in the first embodiment. The type of metal ions is not particularly limited, other than the sodium salt exemplified in the Examples can be used potassium salt and the like. In particular, sodium ions or potassium ions than those that can be a strong base, it is easy to build a pH buffer system in combination with the weak acid. Further, as described above, sodium chloride is the most important salt is essential in vivo, it is preferred that at least sodium chloride is used as a source of sodium ions. Therefore, more preferably used are sodium ions as the metal ions. Also, depending on the degree of adjustment of the pH, as exemplified in Examples 8, weak acid metal salts such as sodium citrate may not be included.

[0111]

　Will now be described technique (2). By bubbling carbon dioxide relative to prepared standard solution can be adjusted to an initial low pH of the standard solution. Bubbling conditions (bubbling method, bubbling time, etc.) at this time is not particularly limited, may be suitably used a known method. The standard solution was bubbled need not dissolved until carbon dioxide is saturated by bubbling, it is sufficient that less 0.4 less than the initial pH is based pH standard solutions . In Examples described later, Example 9 corresponds to the method (2).

[0112]

　Will now be described technique (3). Against prepared standard solution by adding an acid, it is possible to adjust an initial low pH of the standard solution. Here, the type of acid to be added is not particularly limited, as long as it does not affect such degradation or deterioration of the component contained in the standard solution, may be any acid. Specifically, for example, hydrochloric acid, nitric acid, strong acid such as sulfuric acid; organic acids described as a pH adjusting agent in the first embodiment; A agents that can be incorporated into the acid component (acetic acid, citric acid, lactic acid, hydrochloric acid, etc.) and the like can be given; (citric acid, oxalic acid, tartaric acid, maleic acid, ascorbic acid, oxaloacetic acid, gluconic acid, isocitric acid, malic acid, and pyruvate). These acids may as long only one type is used, may be used in combination of two or more as appropriate.

[0113]

　Here, in the method of (3), since it is better to satisfactorily reduce the initial pH in amount as small as possible, hydrochloric acid, nitric acid, a strong acid is preferably used such as sulfuric acid, among others, is the electrolyte components contained in the standard solution hydrochloric acid is preferably used. The concentration of the acid is not particularly limited, as long as thin enough to be adjusted lower at 0.4 within than the reference pH initial pH. Particularly, the case of using hydrochloric acid, pH from the standpoint of easily adjusting the dropwise dilute hydrochloric acid is preferably used. In Examples described later, Example 10 corresponds to method (3).

[0114]

　Wherein (1) - (3) In any of the methods (or in other techniques), the degree of lowering the initial pH of the standard solution, the street, is than the reference pH 0.4 within preferable. Reducing the initial pH beyond 0.4, pH of the filled standard solutions even increased during storage, becomes lower than the reference pH, there may not be properly utilized as a standard solution. For example, if the standard solution is citric acid, it is possible to set a 7.85 manner, as a reference pH of the dialysis solution of Comparative Example 13 described later. In this case, less than 7.85 the initial pH of the standard solution 7.45 or more, preferably about 7.5 (e.g., in the range of 7.45 to 7.65) by adjusting the, as in Examples 7-10 , the highest value of the pH during storage 7.85 before and after (e.g., within the range of 7.7 to 8.0) can be maintained. However, as in Comparative Example 14, the initial pH of the standard solution, if lower beyond 0.4, and remains lower highest pH during storage.

[0115]

　Here, as described in the second embodiment, the standard solution fillers, the void portions are present, bicarbonate of standard solution is decomposed into carbon dioxide, pH over time of being released into the air gap which leads to Do not rise. Therefore, in this embodiment, for example, the (1) In any of the methods to (3), the volume of the void portions is excessively large, there may not be effectively suppress an increase in pH during storage. Therefore, it the present embodiment, the (1) - In any of the method (3) (or other techniques), it is preferably 75% or more filling rate of the standard solution is 70% or more It is more preferable.

[0116]

　As in the first embodiment, (4) together with the standard solution in a sealed container, even a method of filling composed fill gas from an air or nitrogen gas and carbon dioxide, the initial pH of the standard solution can be lowered by 0.4 within than the reference pH (e.g., see the like examples 1-4, 1 day results in Figure 1 and Figure 2 described below). Therefore, configurations disclosed in the first embodiment can be said to be a form of arrangement that is disclosed in the third embodiment.

[0117]

　Further, as described above, even the third embodiment, as in Embodiment 1 or 2 of the embodiments has illustrated the dialysate as bicarbonate-containing formulation to be filled into the sealed container, the present disclosure is not limited thereto , bicarbonate-containing formulation contains bicarbonate (bicarbonate), as long as it is used in the preparation of the dialysate. Therefore, also in the third embodiment, to B agent may be filled in a sealed container as bicarbonate-containing formulation, other bicarbonate-containing formulation may be filled into the sealed container.
Example

[0118]

　The present invention, examples will be specifically described more based on Comparative Examples and Reference Examples, the present invention is not limited thereto. Those skilled in the art without departing from the scope of the present invention, various modifications can be made modifications and alterations.

[0119]

　(Dialysate standard solution preparation of)
　the A agent, sodium chloride 183 g / L, potassium chloride 5.5 g / L, calcium chloride dihydrate 8.1 g / L, magnesium chloride hexahydrate 3.8 g / L, anhydrous citric acid 3.9 g / L, and used those containing sodium citrate hydrate 1.4 g / L, as a B agent, sodium chloride 2.35 g / L and sodium hydrogen carbonate 5.92 g / L I was used to. By diluting a mixture of A agent 27.2mL and B agent 49.7mL dialysis water, to prepare a standard solution of 1L.

[0120]

　(Example 1)
　in glass vials 10mL capacity to fill such that 80 volume% of the standard solution described above, carbon dioxide 12% by volume and air 88% by volume of the mixed gas used as the filler gas, it It filled so that 20 volume%, was hermetically sealed with a rubber stopper with an aluminum cap. Thus to prepare standard solutions filling of Example 1 (production).

[0121]

　Was stored standing up to two weeks at room temperature the standard solution packing (within the range of normal temperature (25 ℃ ± 15 ℃)). Commercially available pH meter (Horiba Ltd., trade name LAQUAtwin B712) using, as well as measuring the pH of the standard solution before filling, after 1 day storage, and after 1 week storage, the pH of the standard solution after 2 weeks of storage They were measured, respectively. The results in the graph of black rhombuses symbols of FIGS. Incidentally, pH of the dialysate standard solution before filling was 7.8.

[0122]

　(Example 2)
　as a filler gas, except for using carbon dioxide 19 vol% and air 81% by volume of the filler gas is the the same manner as in Example 1 to prepare a standard solution filling of Example 2 (production) with, before filling, after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of filled circles symbols of FIG. Incidentally, pH of the standard solution before filling was 7.8.

[0123]

　(Comparative Example 1)
　as a filler gas, with the exception of using air alone (100% by volume air) is Similarly prepared standard solutions packing of Comparative Example 1 as in Example 1 (preparation), prior to filling, after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of the white rectangular symbols of FIG. Incidentally, pH of the standard solution before filling was 7.8.

[0124]

　(Comparative Example 2)
　as a filler gas, except for using nitrogen (100 vol% nitrogen), as well as to prepare a standard solution filling of Example 1 compared in the same manner as in Example 2 (preparation), prior to filling, storage after 1 day, after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of the white triangle symbols in FIG. Incidentally, pH of the standard solution before filling was 7.9.

[0125]

　(Comparative Example 3)
　as the filler gas, with the exception of using only carbon dioxide (100% by volume of carbon dioxide) is to prepare a standard solution filling of Comparative Example 3 in the same manner as in Example 1 (preparation), filled before, after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of white circles symbols of FIG. Incidentally, pH of the standard solution before filling was 7.9.

[0126]

　(Examples 1 and 2, Comparative Example Comparison 1-3)
　As apparent from the results of Examples 1 and 2, by using a mixed gas containing in the range of carbon dioxide 3-20% by volume filler gas if prepared standard solutions packing, even when stored for 2 weeks, pH of the standard solution without excessively lowered, and was able to maintain a range of pH 7.4 ~ 8.0.

[0127]

　On the other hand, as is clear from the results of Comparative Examples 1 and 2, the sealed gas is be manufactured with standard solutions filler alone or only with nitrogen air, resulted in the pH of the standard solution is greater than 8.0. Further, in Comparative Example 3 As it is apparent from the results, when the filler gas is only carbon dioxide, pH at storage Day 1 drops below 7.0 (pH 6.8), after after 1 and 2 weeks both pH was below 7.4 was about 7.0.

[0128]

　In particular, as apparent from FIG. 2, if the filler gas is only carbon dioxide (Comparative Example 3), although initially pH after filling is greatly reduced, according to the present invention (Examples 1 and 2) , it is possible to effectively suppress a significant change in the initial pH.

[0129]

　(Example 3)
　except for using accelerated conditions of 40 ° C. rather than a storage temperature at room temperature, the in the same manner as in Example 1 produce a standard solution filling of Example 3 (preparation) (Therefore, as the filler gas , together with) with carbon dioxide 12 vol% and air 88% by volume of the mixed gas, before filling, after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of black rhombus symbols in FIG. Incidentally, pH of the standard solution before filling was 7.8.

[0130]

　(Example 4)
　except for using accelerated conditions of storage temperature rather than ambient temperature 40 ° C., Example 2 and making a standard solution filling body of Example 4 in a similar manner to (Production) (Therefore, as the filler gas , together with) with carbon dioxide 19 vol% and air 81% by volume of the mixed gas, before filling, after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of filled circles symbols of FIG. Incidentally, pH of the standard solution before filling was 7.8.

[0131]

　(Comparative Example 4)
　except for using accelerated conditions of 40 ° C. rather than a storage temperature at room temperature, the comparing Example 1 and similarly prepared standard solution filling of Comparative Example 4 (Production) (Therefore, as the filler gas with only air was used), before filling, after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of the white rectangular symbols of FIG. Incidentally, pH of the standard solution before filling was 7.8.

[0132]

　(Comparative Example 5)
　except for using accelerated conditions of 40 ° C. rather than a storage temperature at room temperature, the Comparative Example 2 and making a standard solution filling of Comparative Example 5 in the same manner to (Production) (Therefore, as the filler gas with only nitrogen was used), before filling, after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of the white triangle symbols in FIG. 4. Incidentally, pH of the standard solution before filling was 7.9.

[0133]

　(Comparative Example 6)
　except that the storage temperature was accelerated conditions of 40 ° C. instead of room temperature, the is in the same manner as in Comparative Example 3 by making the standard solution filling of Comparative Example 6 (Production) (Therefore, as the filler gas with carbon dioxide alone is used), before filling, after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of white circles symbols of FIG. Incidentally, pH of the standard solution before filling was 7.9.

[0134]

　(Examples 3 and 4, Comparative Examples 4 to comparison 6)
　Examples 3 and 4, Comparative Examples 4-6, since the stored at either 40 ° C., accelerates the increase in pH standard solutions than room temperature storage It has become a condition for. Such as is apparent from the results of Examples 3, 4 was accelerated conditions, by using a mixed gas containing in the range of carbon dioxide from 3 to 20% by volume as a filler gas, standard solutions filler if prepared, even after storage for two weeks, pH of the standard solution without excessively lowered, and was able to maintain a range of pH 7.4 ~ 8.0.

[0135]

　On the other hand, as is clear from the results of Comparative Examples 4 and 5, the filler gas is be manufactured with standard solutions filler alone or only with nitrogen air, resulted in the pH of the standard solution is greater than 8.0. Furthermore, as is clear from the results of Comparative Example 6, when the filler gas is only carbon dioxide, pH is gradually decreased over time, pH was below 7.4 after 2 weeks.

[0136]

　(Example 5)
　in glass vials 10mL volume, filled to be substantially 100 vol% standard solution described above, was hermetically sealed with a rubber stopper with an aluminum cap. Thus to prepare standard solutions filling of Example 5 (production).

[0137]

　And stored by standing up to 4 weeks at room temperature the standard solution packing (within the range of normal temperature (25 ℃ ± 15 ℃)). Commercially available pH meter (Horiba Ltd., trade name LAQUAtwin B712) using, as well as measuring the pH of the standard solution before filling, after 1 day storage and after 1 week storage, after 2 weeks of storage, after storage for 4 weeks the pH of the dialysate standard solution were measured. The results in the graph of black rhombuses symbols of FIGS. Incidentally, pH of the standard solution before filling was 7.8.

[0138]

　(Comparative Example 7)
　in the glass vial, to fill the standard solution such that 80% by volume, except filled with air so that 20% by volume, compared in the same manner as in Example 5 Example 7 thereby producing a standard solution filling body (production), before filling, after storage 1 day, after 1 week storage, after 2 weeks of storage, the pH of the standard solution after 4 weeks of storage were measured. The results in the graph of the white-block symbol of FIG. Incidentally, pH of the standard solution before filling was 7.8.

[0139]

　(Comparative Example 8)
　Except filled with nitrogen instead of air so that 20 volume%, the standard solution packing together to produce (manufacture) of Comparative Example 8 in the same manner as in Comparative Example 7, prior to filling, after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of the white triangle symbols in FIG. Incidentally, pH of the standard solution before filling was 7.9.

[0140]

　(Comparative Example 9)
　except that packed such that 20 volume% of carbon dioxide instead of air, the standard solution packing with Preparation for (production) of Comparative Example 9 in the same manner as in Comparative Example 7, before filling after 1 day storage and after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of white circles symbols of FIG. Incidentally, pH of the standard solution before filling was 7.9.

[0141]

　(Example 6)
　except for using accelerated conditions of 40 ° C. rather than a storage temperature at room temperature, as well as standard solution prepared packings (produced) of Example 6 in the same manner as in Example 5, pre-packed, saving 1 after weeks, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of black rhombus symbols in Fig. Incidentally, pH of the standard solution before filling was 7.7.

[0142]

　(Comparative Example 10)
　in the glass vial, to fill the standard solution such that 70% by volume, to fill the air so that 30 volume%, and accelerated conditions of storage temperature 40 ° C. instead of room temperature except that the, with making a standard solution filling of Comparative example 10 in the same manner as in example 6 (production), before filling, after 1 week storage, after 2 weeks storage, pH of the standard solution after 4 weeks of storage They were measured, respectively. The results in the graph of the white-block symbol of FIG. Incidentally, pH of the standard solution before filling was 7.7.

[0143]

　(Comparative Example 11)
　except that the storage temperature was accelerated conditions of 40 ° C. instead of room temperature, to prepare a standard solution filling of Comparative Example 10 in the same manner as in Comparative Example 8 (preparation) (hence, nitrogen with a standard solution with a packed), before filling, after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of white circles symbols in FIG. Incidentally, pH of the standard solution before filling was 7.8.

[0144]

　(Comparative Example 12)
　except that the accelerated conditions of 40 ° C. rather than a storage temperature at room temperature and in the same manner as in Comparative Example 9 Preparation of standard solution filling of Comparative Example 12 (Production) (thus, dioxide with standard solution with filled with carbon), before filling, after 1 week storage, the pH of the standard solution after 2 weeks of storage were measured. The results in the graph of the white triangle symbols in FIG. Incidentally, pH of the standard solution before filling was 7.9.

[0145]

　(Comparison Examples 5 and 6 and Comparative Examples 7 to 12)
　As is clear from the results of Example 5, (up to a state not overflow beyond or quota) capacity limit of the closed container standard solution filled with standard solution the filling body, for the sealed container is substantially a standard solution only, even after storage for 4 weeks, pH of the dialysate standard solutions without excessively changing, and, pH 7.4 ~ 8.0 We were able to maintain a range of.

[0146]

　On the other hand, as is clear from the results of Comparative Examples 7 and 8, when filled with air or nitrogen with the standard solution, or the pH of the standard solution is increased to 8.0 vicinity, resulting in excess of 8.0. Furthermore, as is clear from the results of Comparative Example 9, when filled with carbon dioxide with the standard solution, pH at storage Day 1 is significantly reduced to less than 7.0 (pH 6.8), after 1 week and 2 both pH after week was below a and 7.4 approximately 7.0.

[0147]

　In Example 6 and Comparative Examples 10 to 6, since the stored standard solution packing in both 40 ° C., which is a condition for accelerating the increase in pH of the dialysate standard solutions than room temperature storage. With such acceleration conditions, or filled with air with a standard solution as in Comparative Example 10, when or filled with nitrogen with a standard solution as in Comparative Example 11, it causes the pH beyond 8.0, When filled with carbon dioxide with a standard solution as in Comparative example 12, it resulted in pH is below 7.4. In contrast, in Example 6, even when stored for 2 weeks at accelerated conditions, pH of the dialysate standard solutions excessively vary without, and to maintain the range of pH 7.4 ~ 8.0 It could be.

[0148]

　(Comparative Example 13)
　as the A agent, sodium chloride 183.0g / L, potassium chloride 5.50 g / L, calcium chloride dihydrate 8.10 g / L, magnesium chloride hexahydrate 3.80 g / L, anhydrous citric acid 3.9 g / L, and used those containing sodium citrate hydrate 1.4 g / L, as a B agent, containing sodium chloride 23.5 g / L and sodium bicarbonate 59.2 g / L using things. By diluting a mixture of A agent 27.2mL and B agent 49.7mL dialysis water, to prepare a standard solution of 1L.

[0149]

　Commercially available pH meter (Horiba Ltd., trade name LAQUAtwin B712) using, was 7.85 was measured the initial pH of the prepared standard solution. Incidentally, the pH = 7.85 is a reference value of pH adjustment (reference pH) in the following Examples 7-10 and Comparative Example 14.

[0150]

　Glass vials 10mL capacity, filling the standard solution such that 80 volume%, was hermetically sealed with a rubber stopper with an aluminum cap. Thus prepared standard solution filling of Comparative Example 13 (manufacture) was.

[0151]

　The standard solution packing was stored to stand at room temperature for 2 weeks (the range of room temperature (25 ℃ ± 15 ℃)). Using the pH meter, a pH of the standard solution was measured several times during storage. The results in the graph of the white triangle symbols in FIG. The maximum value of the pH of the standard solution during storage was 8.13 (after storage for 1 week).

[0152]

　(Example 7)
　the content of sodium chloride in A agent and 183.6g / L, the content of anhydrous citric acid and 4.06 g / L, the content of sodium citrate hydrate 0.35 g / L except that the can in the same manner as in Comparative example 13, was prepared standard solution. The standard solution was 7.55 at the initial pH was measured of. If 7.85 streets reference pH of the, in this embodiment, so that the reference value to adjust the initial pH of the standard solution to reduce about 0.3.

[0153]

　Then, in the same manner as in Comparative Example 13, and the standard solution filling of Example 7 using the standard solution prepared (manufactured). And stored on standing for 12 weeks at room temperature the standard solution filling body in the same manner as in Comparative Example 13. Using the pH meter, after 1 week storage, after 2 weeks of storage, after 4 weeks of storage, after storage for 8 weeks, the pH of the standard solution after 12 weeks of storage were measured. The results by the solid line graph of the black circle symbol in Fig. pH of the standard solution before filling (initial pH) is 7.55 as described above, the maximum value of the pH of the standard solution during storage was 7.85 (after storage for 2 weeks).

[0154]

　(Example 8)
　The content of sodium chloride in A agent and 183.8 g / L, the content of anhydrous citric acid and 4.70 g / L, was not included sodium citrate hydrate (content 0g / L) than are in the same manner as in Comparative example 13, was prepared standard solution. The initial pH of the standard solution was 7.58 was measured. If 7.85 streets reference pH of the, in this embodiment, so that the reference value to adjust the initial pH of the standard solution to reduce approximately 0.27.

[0155]

　Then, in the same manner as in Comparative Example 13, and the standard solution filling of Example 8 using the standard solution prepared (manufactured). The pH of the standard solution was measured several times during storage standard solution packing. The results in the graph of black rhombuses symbols of FIG. The maximum value of the pH of the standard solution during storage was 7.98 (after storage for 2 weeks).

[0156]

　(Comparative Example 14)
　the content of sodium chloride in A agent and 183.8 g / L, the content of anhydrous citric acid and 7.80 g / L, was not included sodium citrate hydrate (content 0g / L) than are in the same manner as in Comparative example 13, was prepared standard solution. The standard solution was 7.30 at the initial pH was measured of. If 7.85 streets reference pH of the, in this comparative example, so that the reference value to adjust the initial pH of the standard solution to reduce approximately 0.55.

[0157]

　Then, in the same manner as in Comparative Example 13, and the standard solution filling material of Comparative Example 14 using the standard solution prepared (manufactured). The pH of the standard solution was measured several times during storage standard solution packing. The results in the graph of white circles symbols of FIG. The maximum value of the pH of the standard solution during storage was 7.74 (after storage for 2 weeks).

[0158]

　(Example 9)
　except for using accelerated conditions of 40 ° C. rather than a storage temperature at room temperature, the standard solution packing together to produce (manufacture) of Example 9 in the same manner as in Example 7, prior to filling, storage 1 after weeks, after 2 weeks of storage, after 4 weeks of storage, after storage for 8 weeks, the pH of the standard solution after 12 weeks of storage were measured. The results by the dotted line graph in black rhombus symbols in Fig. PH of the standard solution before filling (initial pH) is 7.55, the maximum value of the pH of the standard solution during storage was 7.95 (after storage for 1 week).

[0159]

　(Example 10)
　with the preparation of a standard solution of Comparative Example 13 having the same composition prior to filling in glass vials 10mL volume and the standard solution was bubbled with carbon dioxide. The initial pH of the standard solution was bubbled was 7.61. If 7.85 streets reference pH of the, in this example, by bubbling, so that the standard solution the initial pH of about 0.24 is lowered from the reference value of.

[0160]

　Then, in the same manner as in Comparative Example 13, to prepare a standard solution packing of using said standard solution of Example 10 was bubbled (manufactured). The pH of the standard solution was measured several times during storage standard solution packing. The results by the solid line graph of the black circle symbol in Fig. The maximum value of the pH of the standard solution during storage was 7.94 (after storage for 2 weeks).

[0161]

　(Example 11)
　with the preparation of a standard solution of Comparative Example 13 having the same composition prior to filling in glass vials 10mL volume, was added dropwise diluted hydrochloric acid in the standard solution, was adjusted to an initial pH to 7.61 . If 7.85 streets reference pH of the, in this example, with dilute hydrochloric acid, so that the standard solution the initial pH of about 0.24 is lowered from the reference value of.

[0162]

　Then, in the same manner as in Comparative Example 13, manufactured (produced) a standard solution filling of Example 11 using the standard solution was added dropwise diluted hydrochloric acid was. The pH of the standard solution was measured several times during storage standard solution packing. The results by the dotted line graph of black triangles symbols of Figure 10. The maximum value of the pH of the standard solution during storage was 7.94 (after storage for 1 week).

[0163]

　(Example 7 Comparison to 11 and Comparative Examples 13 and 14)
　As is clear from the results of Comparative Example 13, if the initial pH is based pH, the maximum value of the pH during storage is exceeds 8.0 . In contrast, as is clear from the results of Examples 7 and 8, by adjusting the initial pH by adjusting the content ratio of citric acid and sodium ions to decrease within 0.4, pH during storage the highest values can be before or after the reference pH of.

[0164]

　Moreover, as is clear from the results of Examples 7 and 9, even after storage for 12 weeks even when stored for 12 weeks at room temperature storage (Example 7) in accelerated conditions (Example 9), pH of the dialysate standard solution is excessively vary without, it was able to maintain the front and rear reference pH.

[0165]

　Further, in Examples 10 and 11 As is apparent from the results, or bubbling standard solution with carbon dioxide, even or dropwise diluted hydrochloric acid, if lower the initial pH within 0.4, during storage highest pH can be back and forth reference pH. However, as is clear from the results of Comparative Example 14, if lower the initial pH exceeding 0.4, the maximum value of the pH during storage will be significantly less than the reference pH.

[0166]

　Thus, dialysate standard solution filling body according to the present disclosure, as well as dialysate standard solution, filler gas filling of void space of the sealed container is filled with less volume than the standard solution, the filler gas is It consists air or nitrogen gas and carbon dioxide, carbon dioxide content is in the mixed gas in the range of 3 to 20 vol%.

[0167]

　Thus, even if increased pH of the filled dialysate standard solution, it is possible to maintain within the preferred range, also avoids that the insoluble salts are produced in accordance with the pH increase of the dialysate standard solution be able to. Further, it is possible to fill gas is also effectively suppressed significant drop in pH which occurs when only carbon dioxide. Therefore, the dialysate standard solution for a long period of time because it is possible to stably store, it is possible to appropriately adjust the concentration of the dialysis solution prepared at the user site. Accordingly, even when any time preparing dialysate at the user site, without restriction in preparative amounts, it is possible to suppress the variation of the concentration of the dialysate.

[0168]

　Further, in another dialysate standard solution filling body according to the present disclosure, the standard solution, to a volume limit of a closed container, or to the state not overflow beyond the capacity limit of the sealed container is filled to the sealed container . Thus, within the closed container, since substantially only the dialysate standard solution is ready to be filled, avoiding the degradation of the dialysate standard solution of occurrence and bicarbonate carbonates insoluble in carbon dioxide it is possible, it is possible to maintain the pH even after long-term storage within a predetermined range. Therefore, the dialysate standard solution for a long period of time because it is possible to stably store, it is possible to appropriately adjust the concentration of the dialysis solution prepared at the user site. Accordingly, even when any time preparing dialysate at the user site, without restriction in preparative amounts, it is possible to suppress the variation of the concentration of the dialysate.

[0169]

　Furthermore, in addition to the dialysate standard solution filling body according to the present disclosure, the initial pH of the dialysate standard solution after filling the sealed container, and 0.4 within than the pH of the dialysate preparation object (reference pH) It is set lower so. Therefore, it means that by lowering the initial pH in anticipation of increase in the pH of the filled dialysate standard solution in advance. Thus, it is possible even during storage to maintain the pH of the dialysate standard solution within the preferred range, also it is avoided that the insoluble salts are produced in accordance with the pH increase of the dialysate standard solution it can. Therefore, the dialysate standard solution for a long period of time because it is possible to stably store, it is possible to appropriately adjust the concentration of the dialysis solution prepared at the user site. Accordingly, even when any time preparing dialysate at the user site, without restriction in preparative amounts, it is possible to suppress the variation of the concentration of the dialysate.

[0170]

　Here, in all Examples and Comparative Examples described above, by filling a standard solution of dialysate as a bicarbonate-containing formulation in a closed container to prepare a standard solution packings (produced), the stability of the pH of the standard solution It has been evaluated. However, the disclosure is not limited thereto, as also described in the first to third embodiments described above, bicarbonate-containing formulation contains bicarbonate (bicarbonate), used in the preparation of the dialysate as long as it is. Therefore, even in standard solution-filled member as bicarbonate-containing formulation was filled with agent B in a sealed container, even standard solution packing filled with other bicarbonate-containing formulation in a closed container, examples and the like described above is it is needless to say that similar results with.

[0171]

　The present invention is not intended to be limited to the description of the above embodiment, and various modifications are possible within the range shown in the claims, it is disclosed respectively in the form or a plurality of modified examples of different embodiments also included in the technical scope of the present invention embodiment obtained by technical means appropriately combined.

Industrial Applicability

[0172]

　The present invention can be widely used suitably in the field of preparing the dialysis solution used in hemodialysis.

The scope of the claims

[Claim 1]

　A packing filled with standard solution of bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container,
　the sealed container is formed of a material having a gas barrier property,
　in the standard solution the initial pH after filling, characterized in that it is lower than the pH of the bicarbonate-containing formulation prepared target,
standard solutions filler.

[Claim 2]

　The bicarbonate-containing formulation are dialysate,
　the standard solution is at least sodium ion, potassium ion, calcium ion, magnesium ion, bicarbonate and water, was prepared by mixing in a mixing ratio set in advance is intended,
　the initial pH after filling in the standard solution, characterized in that it is low in 0.4 within than the pH of the dialysate preparation object,
standard solution filling body according to claim 1 .

[Claim 3]

　The standard solution
　contains an acid component is a weak acid, sodium ions, potassium ions, and a plurality of kinds of monovalent or divalent metal ions including calcium ions, and magnesium ions,
　the bicarbonate-containing formulation prepared target composition when the reference for the content of the metal ion is equal to the reference, and characterized by having a composition in which the content of the acid component is greater than the reference,
according to claim 1 or standard solution filling body according to 2.

[Claim 4]

　It said acid component is citric acid or acetic acid, wherein the metal salt of the weak acid is sodium or sodium acetate citrate,
standard solution filling body according to claim 3.

[Claim 5]

　The said sealed vessel, wherein is sealed gas-filled filling of void space of the sealed container along with the standard solution,
　the filler gas is composed of air or nitrogen gas and carbon dioxide, the carbon dioxide content characterized in that 3 is a mixed gas in the range of 1-20% by volume,
standard solution filling body according to claim 1 or 2.

[Claim 6]

　The capacity of the sealed container is 100% by volume, in the range filling rate of 70 to 99 vol% of the standard solution, that the filling rate of the filler gas is in the range of 1-30 vol% and wherein,
standard solution filling body according to claim 5.

[Claim 7]

　The standard solution is characterized in that carbon dioxide is bubbled,
standard solution filling body according to claim 1 or 2.

[8.]

　The standard solution is characterized in that the acid is added,
the standard solution filling body according to claim 1 or 2.

[Claim 9]

　A packing filled with standard solution in a sealed container of bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis,
　wherein the closed container is formed of a material having a gas barrier property,
　the standard solutions , until the capacity limit of the closed container, or to the state not overflow beyond the capacity limit of the closed container, characterized in that it is filled to the sealed container,
the standard solution packing.

[Claim 10]

　The bicarbonate-containing formulation are dialysate,
　the standard solution is at least sodium ion, potassium ion, calcium ion, magnesium ion, bicarbonate and water, was prepared by mixing in a mixing ratio set in advance and characterized in that,
the standard liquid filling body according to claim 9.

[Claim 11]

　The total volume of the closed container is 100 vol%, the as standard solutions filling rate is in the range of 80 to 100% by volume, characterized in that it is filled in the closed container,
wherein standard solution filling body according to claim 9 or 10.

[Claim 12]

　Wherein the standard solution of bicarbonate-containing formulation,
　setting sodium ions, potassium ions, and A agent is an aqueous solution of acidic containing calcium ions and magnesium ions, and B containing a bicarbonate, and water, previously the dialysate standard solution was prepared by mixing in a mixing ratio being, or,
　characterized in that it is a standard solution of the B agent,
standard solution filling according to any one of claims 1 to 11 body.

[Claim 13]

　The sealed container is characterized in that at least the body is made of glass,
standard solution filling body according to any one of claims 1 to 12.

[Claim 14]

　Characterized in that it comprises a standard solution filling body according to any one of claims 1 to 13,
a dialysis solution preparation kit.

[Claim 15]

　By filling standard solution bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container, a method for producing a standard solution packing,
　the sealed container, the gas barrier properties It is formed of a material having,
　an initial pH after filling in the standard solution, and adjusting to lower than the pH of the dialysate preparation object,
the manufacturing method of the standard solution packing.

[Claim 16]

　The bicarbonate-containing formulation are dialysate,
　the standard solution, at least, sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, was prepared by mixing in a mixing ratio set in advance ,
　the initial pH after filling in the standard solution, and adjusting to lower in 0.4 within than the pH of the dialysate preparation object,
the standard solution filling body according to claim 15 Production method.

[Claim 17]

　The standard solutions are those containing an acid component is a weak acid, sodium ions, potassium ions, and a plurality of kinds of monovalent or divalent metal ions including calcium ions, and magnesium ions,
　the heavy preparation object the composition of the carbonate-containing formulations when used as a reference, the content of the metal ions equivalent to the reference, and the content of the acid component to more than the reference, adjusting the composition of the standard solution it makes and adjusting the initial pH of the standard solution,
the manufacturing method of the standard solution filling body according to claim 15 or 16.

[Claim 18]

　Said filler gas filling of void space portion in the closed container, so that less volume than the standard solution, by filling the sealed container with the standard solution, to adjust the initial pH,
　the filler gas is consists air or nitrogen gas and carbon dioxide, wherein the carbon dioxide content is a mixed gas in the range of 3 to 20 vol%,
the production of standard solution filling body according to claim 15 or 16 Method.

[Claim 19]

　By bubbling the standard solution with carbon dioxide, and adjusting the initial pH of the standard solution,
the standard solution producing method of filling body according to claim 15 or 16.

[Claim 20]

　By adding an acid to the standard solution, and adjusting the initial pH of the standard solution,
the standard solution producing method of filling body according to claim 15 or 16.

[Claim 21]

　By filling standard solution bicarbonate-containing formulation used in preparing the dialysis fluid for hemodialysis in a sealed container, a method for producing a standard solution packing,
　the sealed container, the gas barrier properties is formed of a material having,
　the standard solution until capacity limit of the closed container, or to the state not overflow beyond the capacity limit of the closed container, characterized in that it is filled into the sealed container,
the standard solution manufacturing method of filling body.

[Claim 22]

　The bicarbonate-containing formulation are dialysate,
　the standard solution, at least, sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water, is prepared by mixing in a mixing ratio set in advance characterized in that,
the manufacturing method of the standard solution filling body according to claim 21.

[Claim 23]

　Wherein a standard solution the standard solution of the dialysate bicarbonate containing formulation,
　sodium ions, potassium ions, and A agent is an aqueous solution of acidic containing calcium ions and magnesium ions, B agent containing the bicarbonate When the or preparing a standard solution of dialysate by mixing in a mixing ratio set and water, previously, or,
　in that the standard solution of the bicarbonate-containing formulation is a standard solution of the B agent wherein,
the production method of the standard solution filling body according to any one of claims 15 to 22.