JP7107400B2 - Standard liquid filling and its use - Google Patents

Description

The present invention provides a dialysate for hemodialysis and a packed body filled with a standard solution used for confirming that the bicarbonate-containing preparation used in preparing the dialysate is used at an appropriate concentration, It also relates to the use of this standard liquid filling.

Hemodialysis therapy (or artificial dialysis therapy; hereinafter abbreviated as “hemodialysis”) is a therapeutic method that is employed for chronic renal failure patients and the like to artificially replace renal function. In hemodialysis, blood is drawn out of the body, passed through a dialyzer, and drawn back into the body. In a dialyzer, the blood and the dialysate are brought into indirect contact with each other through a dialysis membrane, thereby removing waste products from the blood and maintaining electrolytes and water content in the blood. Hemodialysis uses, for example, 100 to 300 liters of dialysate per time.

Dialysates are usually prepared immediately before use. In a general dialysate preparation method, A agent containing electrolyte components and B agent containing hydrogen carbonate (bicarbonate) are mixed immediately before use, and then dialysis water is added. The concentration of each component is thereby adjusted. This is because when part of the electrolyte component contained in agent A coexists with hydrogen carbonate, which is the main component of agent B, they react with each other over time to form an insoluble carbonate. is. The generation of insoluble carbonates will cause precipitation in the dialysate and change the concentration and pH of the components of the dialysate. Also, the bicarbonate contained in the dialysate is decomposed into carbon dioxide over time. This decomposition reaction also changes the component concentration and pH of the dialysate.

Conventionally, as one method for avoiding the generation of insoluble carbonates and the decomposition of bicarbonate ions, for example, as disclosed in Patent Document 1 or 2, agent A and agent B are separated by a partition wall. A method of accommodating each in a multi-chamber container is known. According to this method, the dialysis fluid can be prepared immediately before use by breaking the septum and mixing the A and B agents at the site of use.

JP-A-11-197240 Japanese Patent Application Laid-Open No. 2005-028108

As described above, preparing the dialysate just before use means preparing the necessary amount of dialysate at the site of use as needed. Therefore, compared to preparation of the dialysate while controlling quality on a large scale in a factory or the like equipped with dedicated equipment, variations in the concentration of the dialysate are more likely to occur.

Here, in the method using a multi-chamber container as disclosed in Patent Document 1 or 2, agents A and B can be prepared in advance at a factory, filled in a multi-chamber container and shipped, so dialysis It is possible to suppress variations in the concentration of the liquid. However, in this method, the amount of dialysate prepared is limited to the amount of agent A and agent B that can be accommodated in the multi-chambered container. cannot adequately respond to

SUMMARY OF THE INVENTION The present invention has been made to solve such problems, and it is an object of the present invention to suppress variations in dialysate concentration without limiting the amount of dialysate prepared when the dialysate is prepared as needed at the site of use. The purpose is to provide a possible method.

In order to solve the above-described problems, the standard liquid filling body according to the present disclosure is a filling body in which a standard liquid of a bicarbonate-containing preparation used when preparing a dialysate for hemodialysis is filled in a sealed container. The sealed container is made of a material having gas barrier properties, and the initial pH of the standard solution after filling is lower than the pH of the bicarbonate-containing preparation to be prepared.

According to the above configuration, when the closed container is filled with the bicarbonate-containing formulation used to prepare the dialysate, the initial pH is lowered in anticipation of an increase in the pH of the filled standard solution. As a result, the pH of the standard solution can be maintained within a suitable range even during storage, and the formation of insoluble salts as the pH of the standard solution rises can be avoided. Therefore, the standard solution can be stably stored for a long period of time, and the concentration of the dialysate prepared at the site of use can be appropriately adjusted. As a result, even when the dialysate is prepared as needed at the site of use, variations in the concentration of the dialysate can be suppressed without being subject to restrictions on the amount to be prepared.

In the standard liquid filling body having the above configuration, the bicarbonate-containing preparation is a dialysate, and the standard liquid contains at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate, and water. The initial pH after filling in the standard solution may be lower than the pH of the dialysate to be prepared within 0.4. .

According to the above configuration, when the bicarbonate-containing preparation is dialysate, the initial pH of the filled dialysate standard solution is lowered to within 0.4. Therefore, the pH of the dialysate standard solution can be maintained within a suitable range even during storage, and the formation of insoluble salts accompanying the increase in pH of the dialysate standard solution can be avoided. . Therefore, the dialysis standard solution can be stably stored for a long period of time, and the concentration of the dialysate prepared at the site of use can be appropriately adjusted.

Further, in the standard liquid filling body having the above configuration, the standard liquid contains an acid component which is a weak acid and a plurality of kinds of monovalent or divalent metal ions including sodium ion, potassium ion, calcium ion and magnesium ion. When the composition of the bicarbonate-containing preparation to be prepared is used as a standard, the content of the metal ion is equivalent to the standard, and the content of the acid component is greater than the standard. may be a configuration having

According to the above configuration, the pH is set low by adjusting the content ratio of the weak acid and the metal salt of the weak acid. At this time, since the content ratio of the weak acid and the metal salt of the weak acid is adjusted without substantially changing the metal ion content, the pH is set low while maintaining the substantial composition of the standard solution. be able to. Moreover, when the metal salt of the weak acid is included as the metal ion supply source, the weak acid can behave as an acid in the pH buffer system, and the metal salt of the weak acid can behave as the conjugate base in the pH buffer system. Therefore, depending on the composition of the standard solution, not only is the initial pH lowered in anticipation of an increase in pH, but the pH buffering action of the filled standard solution makes it difficult for the pH to rise.

Further, in the standard liquid filled body having the above configuration, the acid component may be citric acid or acetic acid, and the metal ion serving as the conjugate base may be sodium ion.

Alternatively, in the standard liquid-filled body having the above configuration, the sealed container is filled with the standard liquid and a sealed gas that fills a gap in the sealed container, and the sealed gas is air or nitrogen gas. It may be a mixed gas composed of carbon dioxide and having a carbon dioxide content of 3 to 20% by volume.

According to the above configuration, the packing contains at least a standard solution prepared by mixing sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate, and water, and a smaller volume of the standard solution. It is filled with gas, and this filled gas is a mixed gas containing carbon dioxide in the range of 3 to 20% by volume. This makes it possible to substantially lower the initial pH of the standard solution after filling. Therefore, even if the pH of the filled standard solution rises, it can be maintained within a suitable range, and the formation of insoluble salts accompanying the pH rise of the standard solution can be avoided. In addition, it is possible to effectively suppress a drastic decrease in pH that occurs when the enclosed gas is only carbon dioxide.

Therefore, with the standard liquid filling body having the above configuration, the standard liquid can be stably stored for a long period of time. Therefore, when preparing a dialysis fluid at the site of use, the concentration of the prepared bicarbonate-containing preparation can be adjusted appropriately by comparing the standard solution in the standard solution filling unit with the prepared bicarbonate-containing preparation. can be adjusted to As a result, even when the dialysate is prepared as needed at the site of use, variations in the concentration of the dialysate can be suppressed without being subject to restrictions on the amount to be prepared.

Further, in the standard liquid filling body having the above configuration, when the capacity of the closed container is 100% by volume, the filling rate of the standard liquid is in the range of 70 to 99% by volume, and the filling rate of the sealed gas is in the range of 70 to 99% by volume. may be in the range of 1 to 30% by volume.

Further, in the standard liquid filling body having the above configuration, the standard liquid may be one in which the initial pH is lowered by bubbling carbon dioxide.

Moreover, in the standard liquid filling body having the above configuration, the standard liquid may be one in which the initial pH is lowered by adding an acid.

In order to solve the above problems, another standard liquid filling body according to the present disclosure is a filling body in which a standard liquid of a bicarbonate-containing preparation used for preparing a dialysate for hemodialysis is filled in a sealed container. wherein the closed container is made of a material having gas barrier properties, and the standard solution is kept in the closed container until it reaches the capacity limit of the closed container or exceeds the capacity limit of the closed container and does not overflow. It is a filled configuration.

According to the above configuration, the inside of the sealed container is substantially filled with only the standard solution of the bicarbonate-containing preparation. This makes it possible to avoid generation of insoluble carbonate and decomposition of hydrogencarbonate into carbon dioxide in this standard solution, and to maintain the pH within a predetermined range even after long-term storage. Therefore, it becomes possible to stably store the standard solution over a long period of time. As a result, when the dialysis fluid is prepared at the site of use, the concentration of the prepared bicarbonate-containing preparation can be adjusted appropriately by comparing the standard solution in the standard solution filling unit and the prepared bicarbonate-containing preparation. can be adjusted to As a result, even when the dialysate is prepared as needed at the site of use, variations in the concentration of the dialysate can be suppressed without being subject to restrictions on the amount to be prepared.

In the standard liquid filling body having the above configuration, the bicarbonate-containing preparation is a dialysate, and the standard liquid contains at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate, and water. It may be a configuration prepared by mixing at a mixing ratio.

According to the above configuration, the sealed container is substantially filled with only the dialysate standard solution prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate and water. state. As a result, generation of insoluble carbonate and decomposition of hydrogen carbonate into carbon dioxide can be avoided in the dialysate standard solution, and the pH can be maintained within a predetermined range even after long-term storage. Therefore, it becomes possible to stably store the dialysate standard solution over a long period of time.

In the standard liquid filling body having the above configuration, when the total capacity of the closed container is 100% by volume, the standard liquid is filled into the closed container so that the filling rate is within the range of 80 to 100% by volume. It may be a configuration that is

Further, in the standard liquid filling body having any of the above configurations, the standard liquid of the bicarbonate-containing preparation includes agent A, which is an acidic aqueous solution containing sodium ions, potassium ions, calcium ions and magnesium ions, and carbonic acid. The dialysate standard solution or the standard solution of the B agent may be prepared by mixing the B agent containing the hydrogen salt and water at a preset mixing ratio.

Further, in the standard liquid filling body having any one of the above structures, the closed container may have a structure in which at least the main body is made of glass.

The present invention also includes a dialysate preparation kit that includes a standard liquid filling body having any of the configurations described above.

Furthermore, the present invention also includes a method for manufacturing the standard liquid filling body having the above configuration. Specifically, in the method for manufacturing a standard solution-filled body according to the present disclosure, a standard solution of a bicarbonate-containing preparation used for preparing a dialysate for hemodialysis is filled in a closed container to obtain a standard solution. In the method for manufacturing a filling body, the sealed container is made of a material having gas barrier properties, and the initial pH of the standard solution after filling is adjusted to be lower than the pH of the dialysate to be prepared. Any configuration is acceptable.

In the method for producing a standard liquid-packed body having the above configuration, the bicarbonate-containing preparation is a dialysate, and the standard liquid contains at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate, and water. It is prepared by mixing at a preset mixing ratio, and the initial pH after filling in the standard solution is adjusted to be lower than the pH of the dialysate to be prepared within 0.4. good too.

In the method for producing the standard liquid packed body, the standard liquid contains an acid component that is a weak acid and a plurality of kinds of monovalent or divalent metal ions including sodium ion, potassium ion, calcium ion and magnesium ion. When the composition of the bicarbonate-containing preparation to be prepared is used as a standard, the content of the metal ion is equal to the standard, and the content of the acid component is greater than the standard. , the initial pH may be adjusted by adjusting the composition of the standard solution.

In the method for manufacturing the standard liquid-filled body, the sealed container is filled with the standard liquid so that the volume of the sealed gas that fills the void in the closed container is smaller than that of the standard liquid. The initial pH may be adjusted, and the enclosed gas may be a mixed gas composed of air or nitrogen gas and carbon dioxide with a carbon dioxide content of 3 to 20% by volume.

Further, in the method for manufacturing a standard liquid filled body having the above configuration, the initial pH may be adjusted by bubbling carbon dioxide into the standard liquid.

Further, in the method for manufacturing a standard liquid filled body having the above configuration, the initial pH may be adjusted by adding dilute hydrochloric acid to the standard liquid.

Furthermore, another method for manufacturing a standard liquid-filled body according to the present disclosure is to prepare a dialysate standard by filling a sealed container with a standard liquid of a bicarbonate-containing preparation used when preparing a dialysate for hemodialysis. In a method for manufacturing a liquid-filled body, the closed container is made of a material having gas barrier properties, and the standard liquid overflows up to the volume limit of the closed container or exceeds the volume limit of the closed container. It is a configuration in which the sealed container is filled up to the state where it is empty.

In the method for producing a standard liquid-packed body having the above configuration, the bicarbonate-containing preparation is a dialysate, and the standard liquid contains at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate, and water. The composition may be prepared by mixing at a preset mixing ratio.

In the method for producing a standard liquid-packed body having any of the above configurations, the standard liquid of the bicarbonate-containing preparation is the standard liquid of the dialysate, and is acidic and contains sodium ions, potassium ions, calcium ions, and magnesium ions. The standard solution of the dialysate is prepared by mixing the agent A, which is an aqueous solution of, the agent B containing a bicarbonate, and water at a preset mixing ratio, or the agent containing the bicarbonate It is sufficient that the standard solution of the formulation is the standard solution of the B agent.

With the above configuration, the present invention can provide a technique capable of suppressing variations in the concentration of the dialysate without limiting the amount to be prepared when the dialysate is prepared as needed at the site of use. , It has the effect of

FIG. 4 is a graph showing the results of a representative example of the standard liquid-filled body according to the present disclosure and a comparative example thereof, showing the results of changes in pH over time when the standard liquid-filled body was stored at room temperature. FIG. FIG. 2 is a graph showing the results of a comparative example with respect to the example of the standard liquid-filled body shown in FIG. 1, showing the results of changes in pH over time when the standard liquid-filled body was stored at room temperature. FIG. 2 shows the results of representative examples of standard liquid-filled bodies according to the present disclosure and comparative examples, showing the results of changes in pH over time when the standard liquid-filled bodies were stored under accelerated conditions of 40° C. graph. FIG. 4 is a graph showing the results of a comparative example with respect to the example of the standard liquid-filled body shown in FIG. 3, showing the results of pH change over time when the standard liquid-filled body was stored under accelerated conditions of 40° C.; FIG. 10 is a graph showing the results of representative examples of other standard liquid-filled bodies according to the present disclosure and comparative examples, showing the results of changes in pH over time when the standard liquid-filled bodies were stored at room temperature. . FIG. 6 is a graph showing the results of a comparative example with respect to the example of the standard liquid-filled body shown in FIG. 5, showing the results of changes in pH over time when the standard liquid-filled body was stored at room temperature. FIG. 10 is a graph showing results of comparative examples with respect to examples of other standard liquid-filled bodies according to the present disclosure, showing results of changes in pH over time when the standard liquid-filled bodies were stored under accelerated conditions of 40° C. . FIG. 10 is a graph showing the results of an example of another standard liquid-filled body according to the present disclosure, showing the results of changes in pH over time when the standard liquid-filled body was stored at room temperature or under accelerated conditions of 40° C. . FIG. 10 is a graph showing the results of representative examples of other standard liquid-filled bodies according to the present disclosure and comparative examples, showing the results of changes in pH over time when the standard liquid-filled bodies were stored at room temperature. . FIG. 10 is a graph showing the results of representative examples of other standard liquid-filled bodies according to the present disclosure, showing the results of changes in pH over time when the standard liquid-filled bodies were stored at room temperature. FIG.

A standard liquid filling body and a method for manufacturing the same according to the present disclosure are a filling body obtained by filling a closed container with a standard solution of a bicarbonate-containing preparation used when preparing dialysate for hemodialysis, wherein the closed container is It is composed of a material with gas barrier properties. In the present disclosure, when the dialysate is prepared as needed at the site of use, a plurality of configurations can be adopted in order to suppress variations in the concentration of the dialysate without being subject to restrictions on the amount of preparation.

As a typical configuration, the initial pH of the standard solution after filling is lower than the pH of the bicarbonate-containing preparation to be prepared, or the standard solution reaches the capacity limit of the closed container, or the closed container is closed. A configuration in which the closed container is filled to the extent that the capacity limit of the container is exceeded and the container does not overflow can be mentioned.

More specifically, as the former configuration, (1) the standard liquid is filled with a sealed gas that fills the void in the closed container, and the sealed gas is composed of air or nitrogen gas and carbon dioxide, (2) the standard solution is a mixed gas with a carbon dioxide content in the range of 3 to 20% by volume; When the composition of the bicarbonate-containing preparation to be prepared is based on the composition of the bicarbonate-containing preparation to be prepared, the metal ion content is equivalent to the standard, and the acid component is contained (3) a configuration in which the standard solution is one in which the initial pH is lowered by bubbling carbon dioxide; (4) a standard solution in which an acid is added; A configuration in which the initial pH is lowered can be mentioned.

Here, the bicarbonate-containing preparation in the present disclosure may contain bicarbonate (bicarbonate) and be used for preparation of dialysate. A typical example is the dialysate itself. Alternatively, if the dialysate is prepared by mixing agent A, which is an acidic aqueous solution containing sodium ions and the like, agent B, which contains bicarbonate, and water, bicarbonate in the present disclosure Containing formulations also include B agents.

Hereinafter, representative embodiments according to the present disclosure will be specifically described, and in each of the following embodiments, a case where a dialysate is used as a bicarbonate-containing preparation will be described. Of course, the present disclosure is not limited to this, and it goes without saying that the bicarbonate-containing preparation may be the B agent or another preparation for dialysis.

(Embodiment 1)
The dialysate standard fluid packed body according to the present embodiment is a packed body in which a sealed container is filled with a dialysate standard fluid used when preparing a dialysate for hemodialysis. The dialysate standard solution to be filled is prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water at a preset mixing ratio. is an acidic aqueous solution containing sodium ions, potassium ions, calcium ions and magnesium ions, a B agent containing a bicarbonate (bicarbonate), and a preset mixing ratio of water. and those prepared by mixing with. Also, the sealed container is made of a material having gas barrier properties. The sealed container is filled with a dialysate standard solution and a sealed gas that fills the voids in the sealed container. The sealed gas is composed of air or nitrogen gas and carbon dioxide, and the content of carbon dioxide is is a mixed gas within the range of 3 to 20% by volume.

A representative example of the present embodiment will be specifically described below. In the following description, including not only this embodiment but also other embodiments, for convenience of explanation, the dialysate standard fluid filling body is appropriately abbreviated as "standard fluid filling body", and the dialysate standard fluid is appropriately Abbreviated as "standard solution".

[Dialysate standard solution]
In the standard liquid filling body according to the present embodiment, the standard liquid filled in the sealed container is prepared to have an appropriate composition (or an appropriate electrolyte concentration and pH) according to the type of dialysate to be compared. be done. In the following description, the configuration of the standard solution will be described using a typical dialysate as an example.

In the present embodiment, as a general dialysate (that is, a standard solution to be filled in a sealed container), a predetermined amount of agent A containing an electrolyte component and an acid component and agent B containing bicarbonate is added. A two-agent mixed type prepared by mixing and diluting with dialysis water is exemplified. The dialysate preparation method is not limited to such a two-agent mixed type. It may be prepared by mixing at a ratio.

The electrolyte component contained in agent A is not particularly limited, and is appropriately selected according to the type of dialysate. chloride ions; organic anions such as citrate ions, lactate ions, gluconate ions, succinate ions and malate ions; and the like. Since the dialysate usually contains at least sodium ions, potassium ions, calcium ions, and magnesium ions among these electrolyte components, the standard solution according to the present embodiment also contains these electrolyte components. is preferred.

Sodium ions contained in the standard solution are generally supplied from sodium salts. Specific sodium salts are not particularly limited, but examples include sodium chloride, sodium acetate, sodium citrate, sodium lactate, sodium gluconate, sodium succinate, sodium malate and the like. One of these sodium salts may be used alone, or two or more may be used in combination. Especially, sodium chloride is the most important salt that is essential in the body. is preferably at least sodium chloride.

Potassium ions contained in the standard solution are generally supplied from potassium salts. Specific potassium salts are not particularly limited, but examples include potassium chloride, potassium acetate, potassium lactate, potassium citrate, potassium gluconate, potassium succinate, potassium malate and the like. One kind of these potassium salts may be used, or two or more kinds may be used in combination. Especially, potassium chloride, like sodium chloride, is positioned as a particularly important salt in living organisms. At least potassium chloride is preferably used as the potassium salt.

Magnesium ions contained in the standard solution are generally supplied from magnesium salts. Although specific magnesium salts are not particularly limited, examples thereof include magnesium chloride, magnesium acetate, magnesium lactate, magnesium citrate, magnesium gluconate, magnesium succinate, and magnesium malate. Only one type of these magnesium salts may be used, or two or more types may be used in combination as appropriate. Moreover, these magnesium salts may be used in the form of hydrates. A representative magnesium salt can include magnesium chloride.

Calcium ions contained in the standard solution are generally supplied from calcium salts. Specific calcium salts are not particularly limited, but examples include calcium chloride, calcium acetate, calcium lactate, calcium gluconate, calcium succinate, calcium malate and the like. Only one type of these calcium salts may be used, or two or more types may be used in appropriate combination. Moreover, these calcium salts may be used in the form of hydrates. A representative calcium salt can include calcium chloride.

Chloride ions contained in the standard solution are generally supplied from chloride salts. Although specific chloride salts are not particularly limited, chloride salts of the aforementioned monovalent or divalent metal ions such as sodium chloride, potassium chloride, magnesium chloride and calcium chloride can be mentioned. Chloride salts of these metal ions are preferably used because they can be a source of not only chloride ions but also sodium ions, potassium ions, magnesium ions and calcium ions. In addition, one type of these chloride salts may be used, or two or more types may be used in combination as appropriate. Furthermore, when hydrochloric acid is used as the acid component contained in the standard solution, this hydrochloric acid can also be a source of chloride ions.

The organic acid ions contained in the standard solution are also not particularly limited, and, like chloride ions, salts of each organic acid are generally the supply source. Furthermore, when each organic acid is used as the acid component contained in the standard solution, these organic acids can also serve as sources of each organic acid ion.

A specific content of the electrolyte component contained in the standard solution is not particularly limited, and can be appropriately set according to various conditions. Incidentally, among the respective electrolyte components described above, the content of sodium chloride is usually set to the maximum compared to the contents of the other electrolyte components. This is because the content of sodium chloride is set according to the concentration of electrolytes in the blood. The specific content (concentration) of sodium chloride in the prepared dialysate (standard solution to be filled) is, for example, based on the sodium ion content, preferably within the range of 75 mEq/L to 150 mEq/L. can range from 80 mEq/L to 145 mEq/L.

Therefore, agent A may contain a sodium source such as sodium chloride so that the sodium ion content in the standard solution is within the above range. Similarly, with respect to electrolyte components other than sodium ions, the source of each ion should be contained in agent A so that the standard solution has a desired range.

As the acid component contained in agent A, an organic acid or inorganic acid commonly used in the field of dialysate can be suitably used. Specific examples include acetic acid, citric acid, lactic acid, and hydrochloric acid. These acid components may be anhydrides or hydrates. Representative acid components can include acetic acid or citric acid. Also, a salt of an acid component having a buffering action may be added for the purpose of stabilizing the pH. Representative salts include sodium acetate and sodium citrate.

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

If the acid component is contained within a suitable range, the pH of the standard solution can be adjusted within a suitable range. For example, when the acid component is acetic acid (in the case of a standard solution containing acetic acid), the pH is adjusted within the range of 6.5 to 8.0, preferably within the range of 7.1 to 7.4. be able to. Also, when the acid component is citric acid (in the case of a standard solution containing citric acid), the pH is within the range of 7.0 to 8.5, preferably within the range of 7.5 to 8.0. can be adjusted. Therefore, it is sufficient for the standard solution to contain an acid component within the above-mentioned appropriate range in the A agent.

Agent A may contain components other than the electrolyte component and the acid component described above. In other words, the dialysate to be prepared (standard solution to be filled) can contain, in addition to the electrolyte component and the acid component, various components that are acceptable as components of the dialysate. Specific other components include, for example, glucose (glucose), pH adjusters, and the like.

Glucose can be added to the dialysate for the purpose of maintaining blood glucose levels in hemodialysis subjects. The specific content (concentration) of glucose is not particularly limited, and can be appropriately set according to various conditions. A typical glucose content is, for example, in the range of 0 to 2.5 g/L, preferably in the range of 1.0 to 2.0 g/L, in the prepared dialysate (standard solution to be filled). can be mentioned. Therefore, agent A should contain glucose within the appropriate range as described above in the standard solution.

A pH adjuster can be added separately from the acid component contained in the A agent for the purpose of adjusting the pH of the standard solution. In other words, the standard solution may contain a pH adjuster in addition to the acid component for the purpose of assisting the pH adjustment function of the standard solution by the acid component. Examples of specific pH adjusters include organic acids such as citric acid, oxalic acid, tartaric acid, maleic acid, ascorbic acid, oxaloacetic acid, gluconic acid, isocitric acid, malic acid, and pyruvic acid. Only one of these organic acids may be used, or two or more of them may be used in combination. Furthermore, these organic acids may be used as salts such as sodium salts, potassium salts and magnesium salts.

A specific content (concentration) of the pH adjuster is not particularly limited. The pH adjuster can adjust the pH of the prepared dialysate (standard solution to be filled) within a suitable range and does not affect the functions of the electrolyte component and the acid component described above (or these It may be added in an amount that does not interfere with the function of the component. Therefore, even in agent A, it is sufficient that the pH adjuster is contained in such an amount that the pH of the standard solution can be adjusted and the functions of the electrolyte component and the acid component are not affected.

Examples of the bicarbonate (bicarbonate) contained in the agent B include sodium hydrogen carbonate (sodium bicarbonate). A bicarbonate other than sodium hydrogencarbonate may be used, but the bicarbonate contained in the B agent is preferably sodium hydrogencarbonate only. The specific content of bicarbonate is not particularly limited, and can be appropriately set according to various conditions. In general, the dialysate to be prepared (standard solution to be filled) can be in the range of 15 mEq/L to 45 mEq/L, preferably in the range of 25 mEq/L to 40 mEq/L.

Agent B should be composed of at least a bicarbonate such as sodium hydrogencarbonate, but may contain other components. Other components include, for example, sodium chloride. The content of other components is also not particularly limited, and can be appropriately set according to various conditions. Therefore, other ingredients may be added to the B agent to such an extent that they do not affect the function of the bicarbonate.

The aforementioned agent A is formulated as an acidic liquid (aqueous solution) containing at least the electrolyte component and the acid component described above. may be formulated. Even if the B agent is liquid, the concentration of the bicarbonate is not particularly limited. When the bicarbonate contained in agent B is sodium hydrogencarbonate, it can be, for example, within the range of 40 to 80 g/L, preferably within the range of 60 to 80 g/L.

In the standard liquid filling body according to the present embodiment, the standard liquid to be filled in the sealed container is preferably prepared by mixing the above-described agents A and B and diluting the mixture with dialysis water. In other words, the standard solution should be prepared in the same manner as the dialysate that is actually prepared, and then filled in the sealed container. For example, if the acid component is citric acid, the pH of a general dialysate is usually set within the range of 7.4 to 8.0, as in Examples described later. Therefore, the pH of the standard solution should also be adjusted within this range. A specific method for preparing the standard solution, including adjustment of pH, is not particularly limited, and may be the same as a general dialysate preparation method.

[Sealed container]
In the standard liquid filling body according to the present embodiment, the specific type of the sealed container filled with the standard liquid is not particularly limited. As the airtight container, any known container can be suitably used as long as it has airtightness and gas barrier properties to the extent that it can stably hold the filled standard solution and the later-described sealed gas.

A typical closed container is a glass container in which at least the container body is made of glass. Specific examples of glass containers include vials, ampoules, cartridges, and the like. Although it is necessary to prepare a large amount of the dialysate, a small volume of the standard solution, which is used as a standard for the preparation of the dialysate, may be used. Therefore, a small-volume glass container such as a vial or ampoule used for injections is preferably used. be able to. A syringe can also be used as a glass container depending on the use conditions of the standard solution.

If the sealed container is a vial or the like, a plug member is used to hermetically seal the opening. A specific plug member is not particularly limited, and a known plug member that has substantially no effect on the standard solution and can suitably hermetically seal the opening of a vial or the like is preferably used. can be used. When the sealed container is a vial, a known rubber stopper, silicone stopper, cork stopper, or the like can be suitably used as the stopper member. In addition, in order to improve the reliability of hermetic sealing, a cap made of aluminum or its alloy can be used together.

Moreover, as a closed container, a well-known resin container (resin container) can be suitably used other than a glass container. In such a resin container, the container body may be made of a hard resin material, or may be made of a soft resin material having softness or flexibility. When the sealed container is a resin container having an opening like the vial described above, a known plug member for hermetically sealing the opening may be used in the same manner as the vial.

The capacity of the closed container is not particularly limited. The amount of the standard solution that can be used to confirm the concentrations of the electrolyte component, acid component, and bicarbonate (and other components) contained in the dialysate is required when the dialysate is prepared. Therefore, the capacity of the closed container should be equal to or greater than the amount of the standard solution required for confirming the concentration of each component. As will be described later, the standard liquid filling body according to the present embodiment is filled with not only the standard liquid but also the sealed gas. . Therefore, the capacity of the sealed container should have a capacity that takes into consideration the required amount of the standard solution and the filling amount of the enclosed gas.

[Filling of dialysate standard solution]
The standard liquid filling body according to the present embodiment mixes at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate and water at a preset mixing ratio (as described above, a preferred example A standard solution is prepared by mixing agent A and agent B and diluting with dialysis water, and the standard solution is filled in a closed container and hermetically sealed to produce (manufacture). At this time, in addition to the standard liquid, the sealed container is filled with a sealed gas having a volume smaller than that of the standard liquid.

The sealed gas filled in the sealed container may be air or a mixed gas of nitrogen and carbon dioxide (carbon dioxide), but the upper limit of the content of carbon dioxide in the mixed gas is 20% by volume or less. It has become. As a result, it is possible to effectively suppress volatilization of hydrogen carbonate from the standard solution, so that it is possible to suppress the increase in pH over time. Moreover, since the content of carbon dioxide in the enclosed gas is not excessive, it is possible to effectively suppress a significant decrease in pH due to dissolution of carbon dioxide.

If the carbon dioxide content exceeds 20% by volume, the carbon dioxide will be dissolved excessively in the standard solution, and the pH of the standard solution in the standard solution filling body will reach a preferable lower limit (for example, if the acid component is a citric acid component, the pH of the standard solution will reach a lower limit of 7.0%). 4). If the pH of the standard solution falls below the prescribed range, the concentration of each component in the standard solution will deviate from the prescribed range, and as a result, the standard solution cannot be used. Moreover, the lower limit of the content of carbon dioxide in the mixed gas may be 3% by volume or more. If the carbon dioxide content is less than 3% by volume, the pH of the standard solution may exceed the preferred upper limit (for example, 8.0 if the acid component is citric acid) in the standard solution packed body. If the pH of the standard solution exceeds the specified range, the concentration of each component of the standard solution will deviate from the specified range, as with the decrease in pH, and as a result, the standard solution cannot be used.

In the standard liquid filling body, the sealed gas should be filled so as to fill the gap in the closed container, but the filling rate (filled volume) of the sealed gas in the sealed container is less than the filling rate of the standard liquid. is preferred. Specifically, when the capacity of the closed container is 100% by volume, the filling rate of the standard solution may be 50% by volume or more, preferably in the range of 70 to 99% by volume, and 80 to 95% by volume. Within the range can be mentioned more preferably. Therefore, the filling rate of the sealed gas may be less than 50% by volume, preferably in the range of 1 to 30% by volume, more preferably in the range of 5 to 20% by volume. If the filling rate of the sealed gas is higher than the filling rate of the standard liquid, the carbon dioxide in the sealed gas may dissolve excessively in the standard liquid, and the pH of the standard liquid may drop below the preferred lower limit in the standard liquid filled body.

The method of filling the sealed container with the standard solution and the sealed gas is not particularly limited, and methods known in the field of dialysate or drug packaging can be suitably used. The method for preparing the mixed gas, which is the enclosed gas, is not particularly limited, either, and a known technique can be suitably used. Also, the method of filling the closed container with the standard liquid and the filled gas and hermetically sealing the container is not particularly limited, and a known method can be suitably used.

[Use of standard liquid packing]
The standard fluid filling body according to the present embodiment can be used to check each component contained in the dialysate when preparing the dialysate at the dialysis site. Specifically, for example, the agent A and agent B are mixed and diluted with dialysis water at the dialysis site to prepare a dialysate, and the dialysate is sampled to measure the concentration of the electrolyte component. Also, the standard solution filling body is opened and the standard solution is sampled to measure the concentration of the electrolyte component. The concentrations of the electrolyte components in the dialysate are compared with those in the standard solution, and the concentrations are almost the same, or the concentrations of the electrolyte components in the dialysate are compared with those in the standard solution. is within the allowable range.

If the concentrations of the dialysate are approximately the same, or if the concentrations of the electrolyte components in the dialysate are within the permissible range, the dialysate is prepared with a suitable concentration of the electrolyte components. On the other hand, if the concentrations are different from each other and out of the allowable range, the concentrations of the electrolyte components in the dialysate are adjusted as appropriate, and the concentration comparison between the dialysate and the standard solution is repeated. The method for measuring the concentration of the electrolyte component used at this time is not particularly limited, and a commercially available measuring device, a known measuring method, or the like may be used. In addition, since the pH of the standard fluid is maintained within a predetermined range in the standard fluid filling body, the pH of the prepared dialysate and the pH of the standard fluid can be compared. The pH measurement method used at this time is not particularly limited, and a commercially available pH measurement device, a pH measurement method, or the like may be used.

The standard liquid filling body according to this embodiment can be stored at room temperature for a predetermined storage period. As shown in Examples described later, the standard liquid-filled body according to this embodiment can be stored at room temperature for at least two weeks. In addition, as shown in Examples described later, the pH can be maintained within a predetermined range even when stored under accelerated conditions of 40° C. for two weeks. It is also possible to save. Furthermore, by appropriately setting the storage conditions, it is also possible to store for about one year. The room temperature referred to here may be within the normal temperature range (20±15° C., 5 to 35° C.) defined by JIS.

As described above, the standard liquid-filled body according to the present embodiment can be suitably used for the preparation of dialysate, but the method of using the standard liquid-filled body is not limited only to the preparation of dialysate. It can be used as one of the components of a dialysate preparation kit. Therefore, the present embodiment also includes a dialysate preparation kit containing a standard liquid filled body or an evaluation kit for evaluating the quality of the dialysate. The dialysate preparation kit or evaluation kit should include at least the above-described standard fluid filling body, and other elements constituting these kits are not particularly limited.

For example, in the case of a dialysate preparation kit, the above-mentioned A agent and B agent may be made into a kit together with the standard liquid filling body. Alternatively, in the case of a dialysate evaluation kit, an instrument for sampling the dialysate, an instrument (or measuring instrument) used for measuring the concentration of electrolyte components, an instrument (or measuring instrument) used for measuring the pH, along with the standard liquid filling body Alternatively, measuring instruments) and the like may be made into a kit.

Furthermore, the present embodiment also includes a manufacturing method (manufacturing method) of the standard liquid filling body described above. For example, as a method for manufacturing a standard liquid-filled body according to the present embodiment, a dialysate standard liquid used for preparing a dialysate for hemodialysis is filled in a closed container to obtain a dialysate standard liquid. A method for manufacturing a packing, wherein a standard solution is prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate and water at a preset mixing ratio, and sealed The container is made of a material with gas barrier properties, and the sealed container is filled with the standard liquid so that the volume of the sealed gas that fills the voids in the sealed container is smaller than that of the standard liquid. For example, it is a mixed gas composed of nitrogen gas and carbon dioxide, and the content of carbon dioxide is in the range of 3 to 20% by volume.

In such a method for producing a standard liquid packed body, the standard liquid contains, as described above, agent A, which is an acidic aqueous solution containing sodium ions, potassium ions, calcium ions and magnesium ions, and bicarbonate. It can be prepared by mixing agent B and water at a preset mixing ratio.

As described above, in the present embodiment, the dialysate was exemplified as the bicarbonate-containing preparation to be filled in the sealed container, but the present disclosure is not limited to this, and the bicarbonate-containing preparation is bicarbonate (carbonic acid hydrogen salt) and used for preparation of dialysate. Therefore, in the present embodiment as well, the closed container may be filled with the B agent as a bicarbonate-containing preparation, or another bicarbonate-containing preparation may be filled in the closed container.

(Embodiment 2)
The dialysate standard fluid filling body according to the present embodiment is a filling body obtained by filling a sealed container with a dialysate standard fluid used when preparing a dialysate for hemodialysis, as in the first embodiment. be. The dialysate standard solution to be filled is prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate (bicarbonate) and water in a preset mixing ratio. Typically, agent A, which is an acidic aqueous solution containing sodium ions, potassium ions, calcium ions, and magnesium ions, agent B containing bicarbonate (bicarbonate), and water are prepared in advance. Examples include those prepared by mixing at a set mixing ratio. Also, the sealed container is made of a material having gas barrier properties. The standard solution is filled in the closed container up to the capacity limit of the closed container or to a state where the closed container does not overflow beyond the capacity limit of the closed container.

A representative example of the present embodiment will be specifically described below. Since the standard liquid used in the standard liquid filling body according to the present embodiment is the same as that described in the first embodiment, a detailed description of the standard liquid will be omitted in the present embodiment.

Moreover, the specific configuration of the sealed container used for the standard liquid filling body according to the present embodiment is not particularly limited, and the sealed container described in the first embodiment can be preferably used. In other words, as the closed container, any known container can be suitably used as long as it has sealing properties and gas barrier properties to the extent that it can stably hold the filled standard solution. Therefore, in the present embodiment, a detailed description of the airtight container is also omitted. As will be described later, the standard liquid filling body according to the present embodiment is filled with the standard liquid so that the inside of the sealed container is substantially filled with the standard liquid. Therefore, the volume of the closed container should have the required volume of the standard solution plus a foreseeable reserve volume.

[Filling of dialysate standard solution]
The standard liquid filling body according to the present embodiment mixes at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate and water at a preset mixing ratio (as described above, a preferred example A standard solution is prepared by mixing agent A and agent B and diluting with dialysis water, and the standard solution is filled in a closed container and hermetically sealed to produce (manufacture). At this time, the standard solution is filled in the closed container up to the capacity limit of the closed container or to a state where the closed container does not overflow beyond the capacity limit of the closed container. As a result, the inside of the sealed container is substantially filled only with the dialysate standard solution, so that the formation of a substantial void inside the closed container is suppressed. If the generation of voids can be substantially avoided, the decomposition of hydrogen carbonate in the standard solution into carbon dioxide and release into the voids can be substantially avoided. can be suppressed.

In the standard liquid packing, when the total capacity of the sealed container is 100% by volume, the standard liquid is filled in the closed container so that the filling rate is ideally within the range of 100% by volume. preferable. However, due to the shape of the closed container, hermetic sealing method, filling method according to the closed container, etc., it may be difficult to fill the closed container so that the filling rate of the standard solution is 100% by volume (or There is a case where it is not necessary to fill to 100% by volume). Therefore, in the present embodiment, the sealed container may be filled with the standard liquid so that the lower limit of the filling rate of the standard liquid is 80% by volume or more. is preferable, and it is more preferable to fill the standard solution so as to be 95% by volume or more.

For example, in Examples and Comparative Examples described later, glass vials are used as closed containers. The container body of a typical vial is cylindrical with substantially the same inner diameter from the bottom to the top of the container. The upper end of the portion is provided with an opening that is hermetically sealed by a plug member. When a vial is used as a sealed container, the standard solution is preferably filled not only in the internal space of the cylindrical container body but also in the internal space from the shoulder to the opening. The internal space does not have to be filled until it is filled with the standard solution.

As described above, the inner diameter of the shoulder is smaller than the container body, and the height of the shoulder is significantly smaller than the height of the container body. Therefore, it can be said that the volume in the shoulder is sufficiently smaller than the volume in the container body, so that the volume in the shoulder can be regarded as an error range when viewed from the total volume of the closed container. Further, when the container main body is filled with the standard liquid, even if the inside of the shoulder portion forms a gap, the standard liquid faces the gap with a very small area and a very small volume. Therefore, it can be considered that carbon dioxide (generated by decomposition of the hydrogen carbonate) is hardly released from the standard solution into the void.

In other words, in the vial, it can be said that at least the state in which the container body is filled has reached the capacity limit, and the internal space of the shoulder is the space outside the capacity limit of the vial. Therefore, if the closed container is a vial, if the container body is filled and the standard solution reaches a part of the shoulder, the volume limit of the vial (closed container) (internal space of the container body) will not be exceeded. It means that the standard solution is filled up to the state. Furthermore, the standard solution can be filled until the internal space of the shoulder is filled. In this case, the standard solution is filled up to the capacity limit of the vial (closed container) (substantially the entire capacity of the closed container).

As the closed container, a glass ampoule can also be used as described above. A typical ampoule has a cylindrical container body, similar to a vial, and a head (neck) located at the top of the container body and having an inner diameter that is significantly smaller than that of the container body and whose tip is melt-sealed. . Since the head (neck) is folded during use, the inside of the cylindrical container body constitutes substantially the entire volume of the closed container.

In other words, even in the ampoule, the state in which the container body is filled has reached the capacity limit, and the internal space of the head (neck) is a space outside the capacity limit of the ampoule. Therefore, if the closed container is an ampoule, if the standard solution fills the main body of the container and partially reaches the head (neck), the standard solution is allowed to exceed the capacity limit of the ampoule (closed container) until it does not overflow. is filled. Furthermore, it is possible to fill the standard solution to the limit as long as it does not interfere with fusion sealing of the tip of the head. In this case, the standard solution is filled up to the capacity limit of the ampoule (closed container).

In addition, the sealed container is composed of a "main body" of the container and a "small-capacity part" such as a shoulder or head (a part with a smaller internal capacity than the main body), such as the vial or ampoule described above. If the volume of the main body alone is 100% by volume (the maximum capacity of the closed container exceeds 100% by volume), the filling rate of the standard solution in the main body is 100% by volume. Exceeding is preferable. In this case, the standard solution extends beyond the volume limitation of the main body to reach the small volume portion such as the shoulder or head. Therefore, the volume of the void remaining inside the small-capacity portion can be sufficiently reduced.

In the present embodiment, the method of filling the sealed container with the standard solution is not particularly limited, and any method known in the field of dialysate or drug packaging can be suitably used. Also, the method of filling the closed container with the standard solution and hermetically sealing the container is not particularly limited, and a known method can be suitably used.

Since the use of the standard liquid filling body according to the present embodiment is also the same as that of the first embodiment, a detailed description of the use thereof will be omitted. Here, as in the first embodiment, the present embodiment also includes the manufacturing method (manufacturing method) of the standard liquid filling body described above. For example, as a method for manufacturing a standard solution-filled body according to the present embodiment, a standard solution of a dialysate used for preparing a dialysate for hemodialysis is filled in a sealed container to obtain a dialysate standard solution. A method for manufacturing a packing, wherein a standard solution is prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate and water at a preset mixing ratio, and sealed The container is made of a material having gas barrier properties, and the standard solution is filled into the closed container up to the volume limit of the closed container or until it does not overflow beyond the volume limit of the closed container. be able to.

Further, as described above, in Embodiment 2, as in Embodiment 1, the dialysate was exemplified as the bicarbonate-containing preparation to be filled in the closed container. Carbonic acid-containing preparations may be those containing bicarbonate (hydrogen carbonate) and used for preparation of dialysate. Therefore, in Embodiment 2 as well, the closed container may be filled with the B agent as a bicarbonate-containing preparation, or another bicarbonate-containing preparation may be filled in the closed container.

(Embodiment 3)
The dialysate standard fluid packed body according to the present embodiment is a sealed container filled with a dialysate standard fluid used when preparing a dialysate for hemodialysis, as in the first or second embodiment. is the body. The dialysate standard solution to be filled is prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, bicarbonate and water at a preset mixing ratio. is an acidic aqueous solution containing sodium ions, potassium ions, calcium ions and magnesium ions, a B agent containing a bicarbonate (bicarbonate), and a preset mixing ratio of water. and those prepared by mixing with. Also, the sealed container is made of a material having gas barrier properties. The initial pH of the dialysate standard solution after filling is lower than the pH of the dialysate to be prepared (reference pH) within 0.4.

A representative example of the present embodiment will be specifically described below. The standard liquid, closed container, filling method, use of the filling body, etc. used in the standard liquid filling body according to the present embodiment are the same as or common to those described in the first or second embodiment. , and detailed description thereof will be omitted in this embodiment.

The “initial pH” in the present embodiment means the pH during the period from immediately after filling the sealed container with the standard solution to the first day. The method of setting the initial pH of the standard solution to within 0.4 lower than the reference pH is not particularly limited, but typically, (1) supplying a weak acid and a monovalent or divalent metal ion to the standard solution; When the metal salt of the same weak acid that is the source is included, the content of metal ions is equivalent to the content of the dialysate to be prepared, and the content of the acid component is A method of adjusting the content of the metal salt of the weak acid so that it exceeds this standard, (2) a method of bubbling the standard solution with carbon dioxide, (3) a method of adding a trace amount of acid, etc.

First, the method (1) will be described. As described in the first embodiment, a typical dialysate is a two-agent mixed type of agent A and agent B, and agent A contains an electrolyte component and an acid component. As the acid component, as described above, acetic acid, citric acid, lactic acid, and hydrochloric acid can be used, and the electrolyte component includes a plurality of monovalent or divalent ions including sodium ion, potassium ion, calcium ion, and magnesium ion. of metal ions are included. As the source of these metal ions, acetates, citrates, lactates, chlorides, etc. of these metal ions can be used.

Therefore, with the composition of the dialysate to be prepared as a standard, the composition of the standard solution is adjusted so that the metal ion content is equivalent to this standard and the acid component content is greater than this standard. Specifically, for example, if a metal salt of a weak acid, which is an acid component, is used as the supply source of metal ions, the metal salt of the weak acid is a factor that raises the pH of the standard solution. Therefore, by increasing the content of the weak acid and decreasing the metal salt of the weak acid, and increasing the amount of other sources of metal ions, the content of metal ions is kept equal to the standard. adjust.

More specifically, in method (1), when the composition of the dialysate to be prepared is taken as the reference composition, the content of metal ions in the composition of the standard solution is compared with the content of the reference composition. It is a range that can be regarded as substantially equivalent, and the content of the acid component in the composition of the standard solution is adjusted to be greater than the content in the standard composition.

For example, in Examples 7 or 8 described later, anhydrous citric acid is used as the acid component of Agent A, and sodium citrate (hydrate) and sodium chloride are used as the source of sodium ions. Therefore, the content of anhydrous citric acid is increased, the content of sodium citrate is decreased, and the content of sodium chloride is increased in order to make the content of sodium ions substantially equivalent to the standard. can reduce the initial pH of the standard solution to within 0.4.

Here, when viewed as components in the standard solution, a weak acid can behave as an acid in a pH buffer system, and any one of metal ions can behave as a conjugate base in a pH buffer system. In Example 7, anhydrous citric acid can behave as a weak acid in a pH buffering system and sodium citrate hydrate can behave as a conjugate base in a pH buffering system. Therefore, not only is the initial pH lowered in anticipation of an increase in pH, but the pH of the dialysate standard solution can be prevented from increasing due to the pH buffering action.

The specific type of the weak acid is not particularly limited, and acetic acid, lactic acid, or the like described in Embodiment 1 can be used in addition to the citric acid exemplified in the Examples. Also, the type of metal ion is not particularly limited, and potassium salts and the like can be used in addition to the sodium salts exemplified in the examples. In particular, sodium ions or potassium ions can be strong bases, and can easily construct a pH buffer system by combining them with weak acids. Moreover, as described above, sodium chloride is the most important salt that is essential in vivo, and it is preferable to use at least sodium chloride as a source of sodium ions. Therefore, sodium ions are more preferably used as metal ions. Also, depending on the degree of pH adjustment, as exemplified in Example 8, a metal salt of a weak acid such as sodium citrate may not be included.

Next, the method (2) will be described. By bubbling carbon dioxide through the prepared standard solution, the initial pH of the standard solution can be adjusted low. The bubbling conditions (bubbling method, bubbling time, etc.) at this time are not particularly limited, and known methods can be suitably used. In addition, the standard solution after bubbling does not need to be dissolved until carbon dioxide becomes saturated, and the initial pH of the standard solution may be lower than the reference pH within 0.4 due to bubbling. . In Examples described later, Example 9 corresponds to the method (2).

Next, the method (3) will be described. By adding an acid to the prepared standard solution, the initial pH of the standard solution can be adjusted to be low. Here, the type of acid to be added is not particularly limited, and any acid may be used as long as it does not decompose or degrade the components contained in the standard solution. Specifically, for example, strong acids such as hydrochloric acid, nitric acid and sulfuric acid; acid components that may be contained in agent A (acetic acid, citric acid, lactic acid, hydrochloric acid, etc.); and organic acids described as pH adjusters in the first embodiment. (citric acid, oxalic acid, tartaric acid, maleic acid, ascorbic acid, oxaloacetic acid, gluconic acid, isocitric acid, malic acid, pyruvic acid, etc.); Only one type of these acids may be used, but two or more types may be used in combination as appropriate.

Here, in the method (3), since it is better to lower the initial pH with as little as possible, a strong acid such as hydrochloric acid, nitric acid, sulfuric acid, etc. is preferably used. Hydrochloric acid is preferably used. Moreover, the concentration of the acid is not particularly limited as long as the initial pH can be adjusted to be lower than the reference pH within 0.4. In particular, when hydrochloric acid is used, dilute hydrochloric acid is preferably used from the viewpoint of facilitating pH adjustment by dropping. In Examples described later, Example 10 corresponds to the method (3).

In any of the methods (1) to (3) (or in other methods), the degree to which the initial pH of the standard solution is lowered is, as described above, within 0.4 of the reference pH. preferable. If the initial pH is lowered beyond 0.4, even if the pH of the filled standard solution rises during storage, it may become lower than the standard pH and may not be used properly as a standard solution. For example, if the standard solution is citric acid, 7.85 can be set as the reference pH of the dialysate as in Comparative Example 13, which will be described later. In this case, if the initial pH of the standard solution is adjusted to less than 7.85 and 7.45 or more, preferably about 7.5 (for example, within the range of 7.45 to 7.65), as in Examples 7 to 10 Additionally, the maximum pH during storage can be maintained at around 7.85 (eg, within the range of 7.7-8.0). However, if the initial pH of the standard solution is lowered beyond 0.4 as in Comparative Example 14, the maximum value of pH during storage remains low.

Here, as described in the second embodiment, in the standard liquid packed body, if there are voids, the hydrogen carbonate in the standard liquid is decomposed into carbon dioxide, which is released into the voids, and the pH changes over time. will lead to a sharp rise. Therefore, in the present embodiment, for example, in any of the above methods (1) to (3), if the volume of the void is too large, there is a possibility that the increase in pH during storage cannot be effectively suppressed. Therefore, in the present embodiment, in any of the methods (1) to (3) (or other methods), the filling rate of the standard solution is preferably 70% or more, more preferably 75% or more. is more preferred.

Note that even with the method of (4) filling a sealed container with a sealed gas composed of air or nitrogen gas and carbon dioxide together with the standard solution as in the first embodiment, the initial pH of the standard solution is The pH can be lowered within 0.4 from the reference pH (see, for example, the results of the first day in Examples 1 to 4 and FIGS. 1 and 2 described later). Therefore, it can be said that the configuration disclosed in the first embodiment is one form of the configuration disclosed in the third embodiment.

Further, as described above, in Embodiment 3, as in Embodiment 1 or 2, the dialysate was exemplified as the bicarbonate-containing preparation to be filled in the sealed container, but the present disclosure is not limited to this. , The bicarbonate-containing preparation contains bicarbonate (hydrogen carbonate) and may be used for the preparation of dialysate. Therefore, in Embodiment 3 as well, the closed container may be filled with the B agent as a bicarbonate-containing preparation, or another bicarbonate-containing preparation may be filled in the closed container.

The present invention will be described in more detail based on Examples, Comparative Examples and Reference Examples, but the present invention is not limited thereto. Various changes, modifications and alterations can be made by those skilled in the art without departing from the scope of the invention.

(Preparation of dialysate standard solution)
As agent A, 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 1.4 g/L of sodium citrate hydrate, and as the B agent, one containing 2.35 g/L of sodium chloride and 5.92 g/L of sodium bicarbonate was used. 1 L of standard solution was prepared by diluting 27.2 mL of agent A and 49.7 mL of agent B in dialysis water.

(Example 1)
A glass vial with a capacity of 10 mL is filled with the above-described standard solution to 80% by volume, and a mixed gas of 12% by volume of carbon dioxide and 88% by volume of air is used as the sealed gas, and this is 20% by volume. and hermetically sealed with a rubber stopper with an aluminum cap. Thus, the standard liquid filling body of Example 1 was produced (manufactured).

This standard liquid-packed body was stored at room temperature (within the range of normal temperature (25° C.±15° C.)) for a maximum of two weeks. Using a commercially available pH meter (manufactured by Horiba, Ltd., trade name LAQUAtwin B712), measure the pH of the standard solution before filling, and measure the pH of the standard solution after 1 day of storage, 1 week of storage, and 2 weeks of storage. were measured respectively. The results are shown in the graphs of black diamond symbols in FIGS. 1 and 2. FIG. The pH of the dialysate standard solution before filling was 7.8.

(Example 2)
A standard liquid filling body of Example 2 was prepared (manufactured) in the same manner as in Example 1 except that a filling gas containing 19% by volume of carbon dioxide and 81% by volume of air was used as the filling gas. After 1 day of storage, 1 week of storage, and 2 weeks of storage, the pH of the standard solution was measured. The results are shown in the graph of the black circle symbol in FIG. The pH of the standard solution before filling was 7.8.

(Comparative example 1)
A standard liquid filling body of Comparative Example 1 was prepared (manufactured) in the same manner as in Example 1 except that only air (100% by volume of air) was used as the filling gas, and before filling, after storage for 1 day, and storage. After 1 week and 2 weeks of storage, the pH of the standard solution was measured. The results are shown in the graph of the white rectangular symbol in FIG. The pH of the standard solution before filling was 7.8.

(Comparative example 2)
A standard liquid filling body of Comparative Example 2 was prepared (manufactured) in the same manner as in Example 1 except that nitrogen (100% by volume of nitrogen) was used as the filling gas. After a week and two weeks of storage, the pH of the standard solution was measured. The results are shown in the graph of the white triangle symbol in FIG. The pH of the standard solution before filling was 7.9.

(Comparative Example 3)
A standard liquid filling body of Comparative Example 3 was prepared (manufactured) in the same manner as in Example 1 except that only carbon dioxide (100% by volume of carbon dioxide) was used as the filling gas, before filling and after 1 day of storage. , 1 week after storage, and 2 weeks after storage, the pH of the standard solution was measured. The results are shown in the graph of the open circle symbol in FIG. The pH of the standard solution before filling was 7.9.

(Comparison of Examples 1 and 2 and Comparative Examples 1 to 3)
As is clear from the results of Examples 1 and 2, if a mixed gas containing carbon dioxide in the range of 3 to 20% by volume is used as the sealed gas to prepare a standard liquid-filled body, it can be stored for two weeks. Also, the pH of the standard solution could be maintained within the pH range of 7.4 to 8.0 without excessively decreasing.

On the other hand, as is clear from the results of Comparative Examples 1 and 2, the pH of the standard liquid exceeded 8.0 when the standard liquid filling body was prepared using only air or nitrogen as the sealed gas. Furthermore, as is clear from the results of Comparative Example 3, when only carbon dioxide was used as the enclosed gas, the pH decreased to less than 7.0 (pH 6.8) on the first day of storage, and after 1 week and 2 weeks, All of them had a pH of about 7.0, which was lower than 7.4.

In particular, as is clear from FIG. 2, when the filled gas is only carbon dioxide (Comparative Example 3), the pH drops significantly in the early stage after filling, but according to the present invention (Examples 1 and 2). , it becomes possible to effectively suppress a large change in initial pH.

(Example 3)
A standard liquid filling body of Example 3 is prepared (manufactured) in the same manner as in Example 1 except that the storage temperature is accelerated at 40° C. instead of normal temperature (thus, as the sealed gas, 12 volumes of carbon dioxide % and 88% by volume of air), and the pH of the standard solution was measured before filling, after 1 day of storage, after 1 week of storage, and after 2 weeks of storage, respectively. The results are shown in the graph of black diamond symbols in FIG. The pH of the standard solution before filling was 7.8.

(Example 4)
A standard liquid filling body of Example 4 is prepared (manufactured) in the same manner as in Example 2 except that the storage temperature is accelerated at 40° C. instead of normal temperature (therefore, as the sealed gas, 19 volumes of carbon dioxide % and 81% by volume of air), and the pH of the standard solution was measured before filling, after 1 day of storage, after 1 week of storage, and after 2 weeks of storage, respectively. The results are shown in the graph of black circle symbols in FIG. The pH of the standard solution before filling was 7.8.

(Comparative Example 4)
A standard liquid filling body of Comparative Example 4 is prepared (manufactured) in the same manner as in Comparative Example 1 except that the storage temperature is accelerated to 40° C. instead of room temperature (therefore, only air is used as the filled gas). ), the pH of the standard solution was measured before filling, after 1 day of storage, after 1 week of storage, and after 2 weeks of storage, respectively. The results are shown in the graph of the white rectangular symbol in FIG. The pH of the standard solution before filling was 7.8.

(Comparative Example 5)
A standard liquid filling body of Comparative Example 5 is prepared (manufactured) in the same manner as in Comparative Example 2 except that the storage temperature is accelerated to 40° C. instead of room temperature (Therefore, only nitrogen is used as the filled gas. ), the pH of the standard solution was measured before filling, after 1 week of storage, and after 2 weeks of storage, respectively. The results are shown in the graph of white triangle symbols in FIG. The pH of the standard solution before filling was 7.9.

(Comparative Example 6)
A standard liquid filling body of Comparative Example 6 is prepared (manufactured) in the same manner as in Comparative Example 3 except that the storage temperature is accelerated at 40° C. instead of room temperature (Therefore, only carbon dioxide is used as the filled gas. The pH of the standard solution was measured before filling, after 1 week of storage, and after 2 weeks of storage, respectively. The results are shown in the graph of the open circle symbol in FIG. The pH of the standard solution before filling was 7.9.

(Comparison of Examples 3 and 4 and Comparative Examples 4 to 6)
In Examples 3 and 4, and Comparative Examples 4 to 6, all of which are stored at 40° C., the conditions are such that the pH increase of the standard solution is accelerated more than room temperature storage. As is clear from the results of Examples 3 and 4, even under such acceleration conditions, a mixed gas containing carbon dioxide in the range of 3 to 20% by volume was used as the sealed gas, and the standard liquid filled body , the pH of the standard solution did not excessively decrease and could be maintained within the range of pH 7.4 to 8.0 even after storage for 2 weeks.

On the other hand, as is clear from the results of Comparative Examples 4 and 5, the pH of the standard liquid exceeded 8.0 when the standard liquid filling body was prepared using only air or nitrogen as the sealed gas. Furthermore, as is clear from the results of Comparative Example 6, when only carbon dioxide was used as the enclosed gas, the pH decreased over time and fell below 7.4 after two weeks.

(Example 5)
A glass vial with a volume of 10 mL was filled with the standard solution described above so as to be approximately 100% by volume, and hermetically sealed with a rubber stopper with an aluminum cap. Thus, the standard liquid filling body of Example 5 was produced (manufactured).

This standard liquid-filled body was stored at room temperature (within the range of normal temperature (25° C.±15° C.)) for up to 4 weeks. Using a commercially available pH meter (manufactured by Horiba, Ltd., trade name LAQUAtwin B712), the pH of the standard solution before filling was measured, and after 1 day of storage, 1 week of storage, 2 weeks of storage, and 4 weeks of storage. The pH of each dialysate standard solution was measured. The results are shown in the graphs of black diamond symbols in FIGS. 5 and 6. FIG. The pH of the standard solution before filling was 7.8.

(Comparative Example 7)
Standard liquid-filled body of Comparative Example 7 in the same manner as in Example 5 except that the glass vial was filled with the standard liquid to 80% by volume and air was filled to 20% by volume. was prepared (manufactured), and the pH of the standard solution was measured before filling, after 1 day of storage, after 1 week of storage, after 2 weeks of storage, and after 4 weeks of storage. The results are shown in the graph of the white rectangular symbol in FIG. The pH of the standard solution before filling was 7.8.

(Comparative Example 8)
A standard liquid-filled body of Comparative Example 8 was prepared (manufactured) in the same manner as in Comparative Example 7 except that nitrogen was filled to 20% by volume instead of air. After 1 week and 2 weeks of storage, the pH of the standard solution was measured. The results are shown in the graph of white triangle symbols in FIG. The pH of the standard solution before filling was 7.9.

(Comparative Example 9)
A standard liquid-filled body of Comparative Example 9 was prepared (manufactured) in the same manner as in Comparative Example 7 except that carbon dioxide was filled to 20% by volume instead of air. After 1 week of storage and 2 weeks of storage, the pH of the standard solution was measured. The results are shown in the graph of the open circle symbol in FIG. The pH of the standard solution before filling was 7.9.

(Example 6)
The standard liquid-filled body of Example 6 was prepared (manufactured) in the same manner as in Example 5 except that the storage temperature was accelerated to 40° C. instead of normal temperature, and before filling, after 1 week of storage, and 2nd storage. After a week, the pH of each standard solution was measured. The results are shown in the graph of black diamond symbols in FIG. The pH of the standard solution before filling was 7.7.

(Comparative Example 10)
The glass vial is filled with the standard solution to 70% by volume and filled with air to 30% by volume, and the storage temperature is accelerated to 40 ° C. instead of room temperature. A standard liquid-filled body of Comparative Example 10 was prepared (manufactured) in the same manner as in Example 6, and the pH of the standard liquid was measured before filling, after 1 week of storage, after 2 weeks of storage, and after 4 weeks of storage. The results are shown in the graph of white rectangular symbols in FIG. The pH of the standard solution before filling was 7.7.

(Comparative Example 11)
A standard liquid-filled body of Comparative Example 10 was prepared (manufactured) in the same manner as in Comparative Example 8 except that the storage temperature was accelerated at 40° C. instead of normal temperature (thus, nitrogen was filled together with the standard liquid). , before filling, after 1 week of storage, and after 2 weeks of storage, the pH of the standard solution was measured. The results are shown in the graph of the white circle symbol in FIG. The pH of the standard solution before filling was 7.8.

(Comparative Example 12)
A standard liquid-filled body of Comparative Example 12 is prepared (manufactured) in the same manner as in Comparative Example 9 except that the storage temperature is accelerated to 40 ° C. instead of room temperature (therefore, carbon dioxide is filled together with the standard liquid). At the same time, the pH of the standard solution was measured before filling, after 1 week of storage, and after 2 weeks of storage. The results are shown in the graph of white triangle symbols in FIG. The pH of the standard solution before filling was 7.9.

(Comparison of Examples 5 and 6 and Comparative Examples 7 to 12)
As is clear from the results of Example 5, in the standard liquid filling body in which the standard liquid is filled up to the capacity limit of the closed container (or to the point where it does not overflow beyond the capacity limit), the inside of the closed container is substantially only the standard solution. Therefore, even after storage for 4 weeks, the pH of the dialysate standard solution did not change excessively and could be maintained within the pH range of 7.4 to 8.0.

On the other hand, as is clear from the results of Comparative Examples 7 and 8, when the standard solution was filled with air or nitrogen, the pH of the standard solution increased to around 8.0 or exceeded 8.0. Furthermore, as is clear from the results of Comparative Example 9, when carbon dioxide was filled together with the standard solution, the pH significantly decreased to less than 7.0 (pH 6.8) on the first day of storage, and after 1 week and 2 After a week, the pH was about 7.0 and below 7.4.

In Example 6 and Comparative Examples 10 to 6, since the standard liquid-filled body was stored at 40° C., the conditions were such that the pH increase of the dialysate standard solution was accelerated more than room temperature storage. Under such acceleration conditions, if air is filled together with the standard liquid as in Comparative Example 10, or if nitrogen is filled together with the standard liquid as in Comparative Example 11, the pH will exceed 8.0, Filling carbon dioxide together with the standard solution as in Comparative Example 12 resulted in a pH below 7.4. On the other hand, in Example 6, the pH of the dialysate standard solution did not change excessively and was maintained within the range of pH 7.4 to 8.0 even when stored under accelerated conditions for 2 weeks. was made.

(Comparative Example 13)
As agent A, sodium chloride 183.0 g/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 1.4 g/L of sodium citrate hydrate, and as the B agent, one containing 23.5 g/L of sodium chloride and 59.2 g/L of sodium bicarbonate was used. 1 L of standard solution was prepared by diluting 27.2 mL of agent A and 49.7 mL of agent B in dialysis water.

The initial pH of the prepared standard solution was measured using a commercially available pH meter (trade name: LAQUAtwin B712, manufactured by Horiba, Ltd.) and found to be 7.85. This pH=7.85 is the reference value (reference pH) for pH adjustment in Examples 7 to 10 and Comparative Example 14 below.

A glass vial with a capacity of 10 mL was filled with the standard solution to 80% by volume, and hermetically sealed with a rubber stopper with an aluminum cap. Thus, a standard liquid filling body of Comparative Example 13 was produced (manufactured).

This standard liquid-filled body was stored at room temperature (within the range of normal temperature (25° C.±15° C.)) for two weeks. Using the pH meter, the pH of the standard solution was measured multiple times during the storage period. The results are shown in the graph of white triangle symbols in FIG. Moreover, the maximum pH value of the standard solution during the storage period was 8.13 (after 1 week of storage).

(Example 7)
Except that the content of sodium chloride in agent A was 183.6 g / L, the content of anhydrous citric acid was 4.06 g / L, and the content of sodium citrate hydrate was 0.35 g / L, A standard solution was prepared in the same manner as in Comparative Example 13. The initial pH of this standard solution was measured to be 7.55. Assuming that the reference pH is 7.85 as described above, in this example, the initial pH of the standard solution was adjusted to be about 0.3 lower than the reference value.

Then, in the same manner as in Comparative Example 13, a standard liquid-filled body of Example 7 was produced (manufactured) using the standard liquid. As in Comparative Example 13, this standard liquid-filled body was stored at room temperature for 12 weeks. Using the pH meter, the pH of the standard solution was measured after 1 week of storage, 2 weeks of storage, 4 weeks of storage, 8 weeks of storage, and 12 weeks of storage. The results are shown in the solid-line graph of black circle symbols in FIG. The pH of the standard solution before filling (initial pH) was 7.55 as described above, and the maximum pH value of the standard solution during storage was 7.85 (after 2 weeks of storage).

(Example 8)
The content of sodium chloride in agent A was 183.8 g / L, the content of anhydrous citric acid was 4.70 g / L, and sodium citrate hydrate was not contained (content 0 g / L). A standard solution was prepared in the same manner as in Comparative Example 13. The initial pH of this standard solution was measured to be 7.58. Assuming that the reference pH is 7.85 as described above, in this example, the initial pH of the standard solution was adjusted to be about 0.27 lower than the reference value.

Then, in the same manner as in Comparative Example 13, a standard liquid-filled body of Example 8 was prepared (manufactured) using the standard liquid. The pH of the standard solution was measured multiple times during the storage period of the packed standard solution. The results are shown in the graph of black diamond symbols in FIG. Moreover, the maximum pH value of the standard solution during the storage period was 7.98 (after 2 weeks of storage).

(Comparative Example 14)
The content of sodium chloride in agent A was 183.8 g / L, the content of anhydrous citric acid was 7.80 g / L, and sodium citrate hydrate was not contained (content 0 g / L). A standard solution was prepared in the same manner as in Comparative Example 13. The initial pH of this standard solution was measured to be 7.30. Assuming that the reference pH is 7.85 as described above, in this comparative example, the initial pH of the standard solution was adjusted to be about 0.55 lower than the reference value.

Then, in the same manner as in Comparative Example 13, a standard liquid-filled body of Comparative Example 14 was produced (manufactured) using the standard liquid. The pH of the standard solution was measured multiple times during the storage period of the packed standard solution. The results are shown in the graph of the white circle symbol in FIG. Moreover, the maximum pH value of the standard solution during the storage period was 7.74 (after 2 weeks of storage).

(Example 9)
A standard liquid-filled body of Example 9 was prepared (manufactured) in the same manner as in Example 7 except that the storage temperature was accelerated at 40° C. instead of normal temperature, and before filling, after storage for 1 week, and storage 2. After weeks, after 4 weeks of storage, after 8 weeks of storage, and after 12 weeks of storage, the pH of the standard solution was measured. The results are shown in the dashed line graph of black rhombic symbols in FIG. The pH of the standard solution before filling (initial pH) was 7.55, and the maximum pH value of the standard solution during the storage period was 7.95 (after 1 week of storage).

(Example 10)
A standard solution having the same composition as in Comparative Example 13 was prepared, and carbon dioxide was bubbled through the standard solution before filling a 10 mL glass vial. The initial pH of the standard solution after bubbling was 7.61. Assuming that the reference pH is 7.85 as described above, in this example, bubbling reduced the initial pH of the standard solution from the reference value by about 0.24.

Then, in the same manner as in Comparative Example 13, a standard liquid-filled body of Example 10 was prepared (manufactured) using the standard liquid after bubbling. The pH of the standard solution was measured multiple times during the storage period of the packed standard solution. The results are shown in the solid line graph of black circle symbols in FIG. Moreover, the maximum pH value of the standard solution during the storage period was 7.94 (after 2 weeks of storage).

(Example 11)
A standard solution having the same composition as in Comparative Example 13 was prepared, and diluted hydrochloric acid was added dropwise to the standard solution before filling a 10 mL glass vial to adjust the initial pH to 7.61. Assuming that the reference pH is 7.85 as described above, in this example, the initial pH of the standard solution was lowered from the reference value by about 0.24 using dilute hydrochloric acid.

Then, in the same manner as in Comparative Example 13, a standard liquid filling body of Example 11 was produced (manufactured) using the standard liquid after dropwise addition of dilute hydrochloric acid. The pH of the standard solution was measured multiple times during the storage period of the packed standard solution. The results are shown in the dashed-line graph of black triangle symbols in FIG. Moreover, the maximum pH value of the standard solution during the storage period was 7.94 (after 1 week of storage).

(Comparison of Examples 7 to 11 and Comparative Examples 13 and 14)
As is clear from the results of Comparative Example 13, if the initial pH is the standard pH, the maximum value of pH during storage exceeds 8.0. On the other hand, as is clear from the results of Examples 7 and 8, if the content ratio of citric acid and sodium ions is adjusted to lower the initial pH within 0.4, the pH during storage can be around the reference pH.

Moreover, as is clear from the results of Examples 7 and 9, the pH of the dialysate standard solution was was able to maintain around the reference pH without excessive changes.

Moreover, as is clear from the results of Examples 10 and 11, even if the standard solution is bubbled with carbon dioxide or diluted hydrochloric acid is added dropwise, if the initial pH is lowered within 0.4, the The maximum value of pH can be around the reference pH. However, as is clear from the results of Comparative Example 14, if the initial pH is lowered beyond 0.4, the maximum pH value during storage will be significantly lower than the reference pH.

In this way, the dialysate standard fluid filling body according to the present disclosure is filled with the dialysate standard fluid and the sealed gas that fills the voids in the closed container in a volume smaller than that of the standard fluid. It is composed of air or nitrogen gas and carbon dioxide, and is a mixed gas with a carbon dioxide content in the range of 3 to 20% by volume.

As a result, even if the pH of the dialysate standard solution is increased, the pH of the dialysate standard solution can be maintained within a suitable range, and the formation of insoluble salts accompanying the increase in pH of the dialysate standard solution can be avoided. be able to. Moreover, it is possible to effectively suppress a large decrease in pH that occurs when the enclosed gas is only carbon dioxide. Therefore, the dialysate standard solution can be stably stored for a long period of time, and the concentration of the dialysate prepared at the site of use can be appropriately adjusted. As a result, even when the dialysate is prepared as needed at the site of use, variations in the concentration of the dialysate can be suppressed without being subject to restrictions on the amount to be prepared.

Further, in another dialysate standard solution filling body according to the present disclosure, the standard solution is filled in the closed container to the capacity limit of the closed container or to a state where the closed container does not overflow beyond the capacity limit of the closed container. . As a result, the inside of the sealed container is substantially filled only with the dialysate standard solution, thus avoiding the generation of insoluble carbonate and the decomposition of bicarbonate into carbon dioxide in the dialysate standard solution. In addition, the pH can be maintained within a predetermined range even after long-term storage. Therefore, the dialysate standard solution can be stably stored for a long period of time, and the concentration of the dialysate prepared at the site of use can be appropriately adjusted. Accordingly, even when the dialysate is prepared as needed at the site of use, variations in the concentration of the dialysate can be suppressed without being subject to restrictions on the amount to be prepared.

Furthermore, in another dialysate standard fluid filling body according to the present disclosure, the initial pH of the dialysate standard fluid after being filled in the sealed container is within 0.4 of the pH of the dialysate to be prepared (reference pH). set as low as possible. Therefore, the initial pH is lowered in anticipation of an increase in the pH of the filled dialysate standard solution. As a result, the pH of the dialysate standard solution can be maintained within a suitable range even during storage, and the formation of insoluble salts accompanying the increase in pH of the dialysate standard solution can be avoided. can. Therefore, the dialysate standard solution can be stably stored for a long period of time, and the concentration of the dialysate prepared at the site of use can be appropriately adjusted. As a result, even when the dialysate is prepared as needed at the site of use, variations in the concentration of the dialysate can be suppressed without being subject to restrictions on the amount to be prepared.

Here, in any of the examples and comparative examples described above, the standard solution of the dialysate as the bicarbonate-containing preparation was filled in a sealed container to prepare (manufacture) the standard solution filling body, and the pH stability of the standard solution was measured. is evaluated. However, the present disclosure is not limited to this, and as described in Embodiments 1 to 3 above, the bicarbonate-containing preparation contains bicarbonate (bicarbonate) and is used to prepare a dialysate. Anything that can be done is acceptable. Therefore, even if it is a standard liquid-filled body in which a sealed container is filled with agent B as a bicarbonate-containing preparation, or a standard liquid-filled body in which another bicarbonate-containing preparation is filled in a sealed container, the above-mentioned example etc. Needless to say, similar results are obtained.

It should be noted that the present invention is not limited to the description of the above embodiments, and various modifications are possible within the scope of the claims, and different embodiments and multiple modifications are disclosed respectively. Embodiments obtained by appropriately combining the above technical means are also included in the technical scope of the present invention.

INDUSTRIAL APPLICABILITY The present invention can be widely and suitably used in the field of preparing dialysate used in hemodialysis.

Claims (20)

A packed body obtained by filling a sealed container with a standard solution of a bicarbonate-containing preparation used when preparing a dialysate for hemodialysis,
The sealed container is a vial made of a material having gas barrier properties and having a shoulder portion with an inner diameter narrower than that of the container body and an opening provided at the upper end of the shoulder portion,
the liquid level of the standard liquid is positioned below the plug member that hermetically seals the opening;
The initial pH of the standard solution after filling is lower than the pH of the bicarbonate-containing preparation to be prepared,
Standard liquid filling. A packed body obtained by filling a sealed container with a standard solution of a bicarbonate-containing preparation used when preparing a dialysate for hemodialysis,
The closed container is made of a material having gas barrier properties, and is an ampule having an inner diameter smaller than that of the container body and a head portion whose tip is a melt-sealed portion,
The liquid surface of the standard liquid is positioned below the fusion sealing portion,
The initial pH of the standard solution after filling is lower than the pH of the bicarbonate-containing preparation to be prepared,
Standard liquid filling. the bicarbonate-containing preparation is a dialysate,
The standard solution is prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate and water at a preset mixing ratio,
The initial pH after filling in the standard solution is lower than the pH of the dialysate to be prepared within 0.4,
The standard liquid filling body according to claim 1 or 2 . The standard solution is
Containing an acid component that is a weak acid and multiple types of monovalent or divalent metal ions including sodium ions, potassium ions, calcium ions, and magnesium ions,
When the composition of the bicarbonate-containing preparation to be prepared is used as a standard, the content of the metal ion is equivalent to the standard, and the content of the acid component is higher than the standard. characterized by
A standard liquid filling body according to any one of claims 1 to 3 . The acid component is citric acid or acetic acid, and the metal salt of the weak acid is sodium citrate or sodium acetate,
The standard liquid filling body according to claim 4 . The sealed container is filled with a sealed gas that fills a gap in the sealed container together with the standard liquid,
The enclosed gas is composed of air or nitrogen gas and carbon dioxide, and the content of carbon dioxide is a mixed gas within the range of 3 to 20% by volume.
A standard liquid filling body according to any one of claims 1 to 3 . When the capacity of the closed container is 100% by volume, the filling rate of the standard liquid is in the range of 70 to 99% by volume, and the filling rate of the sealed gas is in the range of 1 to 30% by volume. characterized by
The standard liquid filling body according to claim 6 . The standard solution is characterized in that carbon dioxide is bubbled,
A standard liquid filling body according to any one of claims 1 to 3 . The standard solution is characterized in that an acid is added,
A standard liquid filling body according to any one of claims 1 to 3 . The standard solution of the bicarbonate-containing preparation is
It was prepared by mixing agent A, which is an acidic aqueous solution containing sodium ions, potassium ions, calcium ions and magnesium ions, agent B containing bicarbonate, and water at a preset mixing ratio. a standard solution of the dialysate, or
characterized by being a standard solution of the B agent,
A standard liquid filling body according to any one of claims 1 to 9 . The sealed container is characterized in that at least the main body is made of glass,
A standard liquid filling body according to any one of claims 1 to 10 . characterized by comprising the standard liquid filling body according to any one of claims 1 to 11,
Dialysate preparation kit. A method for producing a standard liquid-filled body by filling a sealed container with a standard liquid of a bicarbonate-containing preparation used when preparing a dialysate for hemodialysis, comprising:
The sealed container is a vial made of a material having gas barrier properties and having a shoulder portion with an inner diameter narrower than that of the container body and an opening provided at the upper end of the shoulder portion,
Positioning the liquid surface of the standard liquid below the plug member that hermetically seals the opening,
The initial pH after filling in the standard solution is adjusted to be lower than the pH of the dialysate to be prepared,
Method for manufacturing a standard liquid filling body. A method for producing a standard liquid-filled body by filling a sealed container with a standard liquid of a bicarbonate-containing preparation used when preparing a dialysate for hemodialysis, comprising:
The sealed container is an ampoule made of a material having gas barrier properties, having an inner diameter smaller than that of the container body, and having a head with a fusion-sealed tip,
Positioning the liquid surface of the standard liquid below the fusion sealing portion,
The initial pH after filling in the standard solution is adjusted to be lower than the pH of the dialysate to be prepared,
Method for manufacturing a standard liquid filling body. the bicarbonate-containing preparation is a dialysate,
The standard solution is prepared by mixing at least sodium ions, potassium ions, calcium ions, magnesium ions, hydrogen carbonate and water at a preset mixing ratio,
The initial pH of the standard solution after filling is adjusted to be lower than the pH of the dialysate to be prepared within 0.4,
15. A method for manufacturing a standard liquid filling body according to claim 13 or 14 . The standard solution contains an acid component, which is a weak acid, and a plurality of monovalent or divalent metal ions including sodium ions, potassium ions, calcium ions, and magnesium ions,
When the composition of the bicarbonate-containing preparation to be prepared is used as a standard, the standard solution is prepared so that the content of the metal ion is equivalent to the standard and the content of the acid component is greater than the standard. The initial pH of the standard solution is adjusted by adjusting the composition of
16. A method for manufacturing a standard liquid filling body according to any one of claims 13 to 15 . The initial pH is adjusted by filling the sealed container together with the standard solution with a sealed gas that fills the void in the sealed container so that the volume is smaller than that of the standard solution,
The enclosed gas is composed of air or nitrogen gas and carbon dioxide, and the content of carbon dioxide is a mixed gas within the range of 3 to 20% by volume.
16. A method for manufacturing a standard liquid filling body according to any one of claims 13 to 15 . The initial pH of the standard solution is adjusted by bubbling the standard solution with carbon dioxide,
16. A method for manufacturing a standard liquid filling body according to any one of claims 13 to 15 . The initial pH of the standard solution is adjusted by adding an acid to the standard solution,
16. A method for manufacturing a standard liquid filling body according to any one of claims 13 to 15 . the standard solution of the bicarbonate-containing preparation is the standard solution of the dialysate,
The dialysis is performed by mixing agent A, which is an acidic aqueous solution containing sodium ions, potassium ions, calcium ions and magnesium ions, agent B containing bicarbonate, and water at a preset mixing ratio. Prepare liquid standards, or
wherein the standard solution of the bicarbonate-containing preparation is the standard solution of the B agent,
20. The method for producing a standard liquid filling body according to any one of claims 13 to 19 .

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