JP4818688B2 - Drug dissolving device - Google Patents

Description

  The present invention relates to a drug dissolution apparatus used for preparing hemodialysis fluid in the medical field, for example.

  Conventionally, for example, in order to prepare hemodialysis fluid (hereinafter simply referred to as “dialysis fluid”) in the medical field, a hemodialysis dry medicine (hereinafter referred to as “dry medicine”) is dissolved in water in a dialysis facility or the like. It is widely done.

  A conventional drug dissolution apparatus used for preparing dialysate includes a dissolution tank, a water supply means for supplying R / O (Reverse Osmosis) water to the dissolution tank, and R / O water supplied to the dissolution tank. A weighing means for weighing, a stirring means for dissolving, for example, a granular dry drug in the measured R / O water, and a means for feeding the solution after dissolving the dry drug from the dissolution tank to the outside. It is equipped with.

  The concentration of dialysate must be properly controlled to an appropriate value because of therapeutic needs. For this reason, conventionally, the drug dissolution apparatus is provided with a concentration detection means for detecting the concentration of the solution of the dry drug. As the concentration detection means, an electric conductivity meter is used because it has many advantages such as a simple configuration, easy handling, and a small amount of variation in measured values and high reliability.

For example, an electrical conductivity meter is provided in a path for circulating the liquid from the dissolution tank, and while detecting the electrical conductivity of the solution, the dry chemical is supplied to the dissolution tank, and the indicated value of the electrical conductivity meter is a predetermined value. At that point, the supply of dry medicine is stopped. Thereby, the solution by which the dry chemical | medical agent was melt | dissolved by the predetermined density | concentration can be obtained (for example, refer patent documents 1-3).
JP-A-7-275354 Japanese Patent Laid-Open No. 10-85573 Japanese Patent Publication No. 1-55893

By the way, even if the solute concentration of the solution is the same, the electrical conductivity of the solution varies depending on the temperature of the solution. Therefore, the electrical conductivity of the solution is generally displayed in terms of electrical conductivity at the reference temperature. The converted value of electrical conductivity is calculated by the following formula 1.
k _T = kt / {1 + α / 100 × (t−T)} (1)
(Where, T is the reference temperature [° C.], t is the temperature of the solution [° C.], k _T is the electrical conductivity converted into T ° C., kt is the electrical conductivity at t ° C., and α is the temperature coefficient of the solution [%]. )

  Usually, the reference temperature T is set to 25 ° C. The temperature coefficient α is generally set as a fixed value (for example, 2.00%).

  And also in the conventional chemical | medical agent melt | dissolution apparatus, the electrical conductivity of the solution was converted into the electrical conductivity in reference | standard temperature, and the temperature coefficient (alpha) was managed as a fixed value.

  However, if the temperature coefficient α is treated as a fixed value, the electrical conductivity is controlled with four-digit accuracy with diluted water having the same temperature as the use environment temperature range (for example, 5 ° C. to 35 ° C.) of the drug dissolving device, A solution having a stable concentration (such as dialysate or dialysate stock solution) could not be prepared.

  Therefore, conventionally, a heating means is provided in the dilution water supply system of the drug dissolving device, and the temperature of the solution is made constant by heating the dilution water to a constant temperature (for example, 28 ° C.). And the density | concentration of the solution was managed based on the comparison with the detected value of the electrical conductivity of the solution of the temperature, and the reference value set in the temperature. Or a heating means may be provided so that the solution itself in a dissolution tank may be heated.

  As described above, a solution having a stable concentration can be prepared by heating the dilution water and the solution itself in the dissolution tank to a constant temperature.

  However, in order to provide the heating means as described above, a corresponding space is required in the drug dissolution apparatus, the apparatus configuration is complicated, and a corresponding cost is required.

  Accordingly, an object of the present invention is to provide a drug dissolution apparatus that can perform more accurate temperature compensation of measured values of electrical conductivity.

  Another object of the present invention is to provide a solution having a predetermined concentration more accurately by measuring the electrical conductivity of the solution more accurately without providing a heating means to keep the temperature of the solution constant. It is an object of the present invention to provide a drug dissolving device that enables the above.

The above object is achieved by the drug dissolving device according to the present invention. In summary, the present invention provides a dissolution tank, a solvent supply means for supplying a solvent to the dissolution tank, a solute supply means for supplying a solute to the dissolution tank, and a temperature for detecting the temperature of the solution in the dissolution tank. meter and an electric conductivity meter for detecting the electrical conductivity of the solution of the dissolution tank, before Symbol formula 1 the measured value of electric conductivity meter,
k _T = kt / {1 + α / 100 × (t−T)} (1)
(Where, T is the reference temperature [° C.], t is the temperature of the solution [° C.], k _T is the electrical conductivity converted into T ° C., kt is the electrical conductivity at t ° C., and α is the temperature coefficient of the solution [%]. )
And a control means for converting into electrical conductivity at a reference temperature T based on the above , and by detecting the electrical conductivity of the solution in the dissolution tank with the electrical conductivity meter, the solvent has a predetermined concentration. In a drug dissolution apparatus for preparing a solution in which the solute is dissolved,
The control means uses information indicating the relationship between the temperature coefficient α obtained in advance according to the type of the solute and the temperature t of the solution, and the temperature coefficient α corresponding to the temperature t of the solution in the dissolution tank. And the conversion is performed based on the equation 1 using the temperature coefficient α corresponding to the obtained temperature t of the solution in the dissolution tank .

According to one embodiment of the present invention, the drug dissolving device further specifies storage means for storing information indicating a relationship between the temperature coefficient α and the temperature t of the solution for each kind of the solute, and specifies the kind of the solute. Input means for inputting a signal to the control means, and the control means includes the temperature coefficient α and the solution stored in the storage means according to the signal designating the type of the solute from the input means. using the information indicating the relationship between the temperature t of, determine the temperature coefficient α corresponding to the temperature t of the solution of the dissolution tank. Further, according to a preferred embodiment, the storage means stores, as information indicating the relationship between the temperature coefficient α and the solution temperature t, for each kind of the solute, a secondary or higher order using the solution temperature t as a variable. The regression constant of the regression equation is stored, and the control means reads the regression constant stored in the storage means according to a signal specifying the type of the solute from the input means, and the regression constant is read. A temperature coefficient α corresponding to the temperature t of the solution in the dissolution tank is calculated from the regression equation used.

According to another embodiment of the present invention, the control means uses the temperature coefficient α corresponding to the temperature t of the solution in the dissolution tank as information indicating the relationship between the temperature coefficient α and the temperature t of the solution, The drug dissolution apparatus further has an input means for inputting a regression constant of the regression equation, calculated from a quadratic or higher-order regression equation with the temperature t of the solution as a variable.

  According to an exemplary embodiment of the present invention, the solute is a hemodialysis dry drug and the solvent is reverse osmosis water.

  According to the present invention, more accurate temperature compensation of the measured value of electrical conductivity can be performed. In addition, according to the present invention, it is possible to measure the electrical conductivity of the solution more accurately without providing a heating means to keep the temperature of the solution constant, and to prepare a solution with a predetermined concentration more accurately. Is possible.

  Hereinafter, the drug dissolution apparatus according to the present invention will be described in more detail with reference to the drawings.

Example 1
[Overall configuration of drug dissolving device]
FIG. 1 shows a schematic configuration of an embodiment of a drug dissolving apparatus according to the present invention. In this embodiment, the drug dissolution apparatus 1 can be suitably used as a dry drug dissolution apparatus for hemodialysis fluid that prepares A liquid of dialysate (or A stock solution that is a concentrated solution of agent A).

  As shown in FIG. 1, the drug dissolving device 1 has a dissolving tank 15. Further, the drug dissolving device 1 has a hopper 11 as a drug storage means for storing the A drug 101 which is a dry drug. The hopper 11 is connected to the dissolution tank 15 via a supply device 13 as a solute supply means.

  An inlet pipe 16 as a solvent supply means for supplying R / O water, which is an aqueous polar solvent, to the dissolving tank 15 is connected to the dissolving tank 15 via an inlet valve 17 that is an electromagnetic valve. In addition, an outlet pipe 18 is connected to the outlet of the dissolution tank 15. The outlet pipe 18 is provided with a pump 19 as a liquid feeding means. The pump 19 is connected to a reflux line 20 for recirculating the liquid sent from the dissolution tank 15 to the dissolution tank 15 again. The pump 19 is connected to a feeding line 21 for feeding a solution having a predetermined concentration prepared in the dissolution tank 15 to a storage tank (not shown).

  The recirculation pipe 20 is provided with a recirculation flow path valve 22 and an electric conductivity meter 24 which are electromagnetic valves. In addition, a feeding path valve 23 that is an electromagnetic valve is installed in the feeding line 21.

  When preparing the liquid A (or A stock solution) of the dialysate with the drug dissolving apparatus 1 of the present embodiment, first, the inlet valve 17 is opened with the annular flow path valve 22 and the supply path valve 23 closed. R / O water is introduced into the dissolution tank 15 through the inlet pipe 16. The amount of water is measured by a float switch 25 as a measuring means provided in the dissolution tank 15. When the amount of water is metered, the inlet valve 17 is closed, the ring passage valve 22 is opened, and the pump 19 is operated with the supply passage valve 23 closed. Thereby, the water in the dissolution tank 15 is circulated through the outlet line 18 and the reflux line 20 and stirred.

  Subsequently, the A agent 101 is continuously supplied from the hopper 11 into the dissolution tank 15 via the supply device 13. Agent A 101 is a powdered drug containing sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, glacial acetic acid, and glucose (glucose) at a predetermined ratio.

  The agent A 101 is stirred and mixed in the dissolution tank 15 by circulating water. At this time, the electrical conductivity meter 24 installed in the reflux conduit 20 detects the electrical conductivity of the liquid flowing in the reflux conduit 20. By detecting this electrical conductivity, the concentration of agent A in the agent A solution can be measured based on the relationship (calibration curve) between the conductivity of agent A solution and the concentration of agent A.

  In this embodiment, the detection signal of the electric conductivity meter 24 is input to the controller 31 through predetermined signal processing such as amplification and A / D conversion in the control unit 30. The storage means 32 of the control unit 30 stores the detected value of the electrical conductivity meter 24 for the agent A solution, which is determined in advance based on the relationship (calibration curve) between the electric conductivity of the agent A solution and the concentration of the agent A 101. The target value is stored. The controller 31 controls the supply device 13 to appropriately supply the agent A 101 and compares the detected value of the electric conductivity meter 24 with the target value to detect that the detected value has reached the target value. Then, the supply of the agent A 101 by the first supply device 13 is stopped. Thereby, the A agent solution containing the A agent 101 having a predetermined concentration, that is, the A solution (or A stock solution) is prepared.

  When the A solution (or A stock solution) having a predetermined concentration is prepared in this way, the circulation passage valve 22 is then closed and the feed passage valve 23 is opened, so that the dissolution tank 15 is opened. The mixed solution in the inside is discharged to the feeding line 21. This mixed solution flows through the supply pipeline 21 and is supplied to a storage tank (not shown).

  For example, a dialysis fluid supply device or a personal dialysis device is connected to the downstream side of the storage tank to which the liquid A prepared by the drug dissolving device 1 is supplied. The dialysate supply device or the personal dialyzer is prepared by using the B solution of dialysate (or B stock solution, which is a concentrated solution of B agent) prepared by another dissolving device, and the A solution prepared by the drug dissolving device 1 ( Or A stock solution) is diluted with R / O water to prepare a dialysate having a predetermined concentration. The dialysate B solution is an aqueous solution having a predetermined concentration of agent B, which is sodium hydrogen carbonate.

  When the above process is completed, the feed passage valve 23 is closed and one melting operation is completed. In the next melting operation, the above-described operation is repeated.

  By the way, as described above, the electric conductivity of the solution varies depending on the temperature of the solution even if the concentration is the same. Therefore, in the drug dissolving device 1 of the present embodiment, the measured value of the electric conductivity meter 24 is managed by converting into the electric conductivity at the reference temperature.

  That is, the drug dissolving device 1 of the present embodiment has a thermometer 26 that detects the temperature of R / O water as a solvent in the inlet pipe line 16. Thereby, the temperature of the solution in the dissolution tank 15 can be detected as a result. The detection signal of the thermometer 26 is input to the controller 31 through predetermined signal processing such as amplification and A / D conversion in the control unit 30. The thermometer 26 may be provided so as to detect the temperature of the solution itself in the dissolution tank 15.

The controller 31 converts the measured value of the electric conductivity meter 24 into the following formula 1,
k _T = kt / {1 + α / 100 × (t−T)} (1)
(Where, T is the reference temperature [° C.], t is the temperature of the solution [° C.], k _T is the electrical conductivity converted into T ° C., kt is the electrical conductivity at t ° C., and α is the temperature coefficient of the solution [%]. )
Is converted into the electrical conductivity at the reference temperature T. In this embodiment, the reference temperature T is 25 ° C.

Here, in the conventional drug dissolving apparatus, the temperature coefficient α is a fixed value (for example, 2.00% ) . This is because, for example, the electrical conductivity of a normal aqueous solution at about room temperature changes by about 2% with a temperature change of 1 ° C., so that in general applications, the temperature coefficient α is set to 2.00% with sufficient accuracy. This is because the electrical conductivity can be measured.

  However, in the drug dissolving apparatus, as described above, when the temperature coefficient α is handled as a fixed value, it is 4 digits in dilution water having the same temperature as the use environment temperature range (5 ° C. to 35 ° C.) of the drug dissolving apparatus. The electrical conductivity cannot be controlled with accuracy. Therefore, conventionally, the temperature of the solution in the dissolution tank is kept constant by providing a heating means for heating the dilution water or a heating means for heating the solution itself in the dissolution tank. For example, 28 ° C.). However, in view of simplification of the configuration of the apparatus and cost reduction, it is desired that the electrical conductivity can be accurately measured without providing such a heating means, and a solution with an accurate concentration can be prepared. .

  As a result of intensive studies by the present inventors, for example, it was confirmed that the temperature coefficient α of the A liquid (or A stock solution) varies depending on the temperature. Then, it was found that the electrical conductivity of the solution at an arbitrary temperature can be accurately compensated by examining the temperature dependence of the temperature coefficient α in advance.

  Further, as a result of the study by the present inventors, it has been found that the temperature dependence of the temperature coefficient varies depending on the type of solute, for example, the type of dry drug for hemodialysis.

  Therefore, in the drug dissolving device 1 of the present embodiment, as will be described in detail later, the controller 31 serving as a control means includes a temperature coefficient α specified according to the type of solute (agent A in the present embodiment) and the solution. The temperature coefficient α is changed according to the temperature t of the solution in the dissolution tank 15 using information indicating the relationship with the temperature t.

  Then, the controller 31 uses the temperature coefficient α thus variable to convert the measured value of the electrical conductivity into the electrical conductivity at the reference temperature according to the above formula 1 and manage it. That is, the target value of the electrical conductivity of the solution having a predetermined concentration is set as the electrical conductivity at the reference temperature, and the measured value of the electrical conductivity of the solution is converted into the electrical conductivity at the reference temperature. It is used for processing such as comparison. Accordingly, it is possible to always prepare a solution having a predetermined concentration accurately regardless of the dilution water, that is, the temperature of the solution.

[Temperature compensation for electrical conductivity]
Next, the temperature compensation of the measured value of the electric conductivity meter 24 in the drug dissolving device 1 of the present embodiment will be described in more detail.

  First, the temperature dependence of the temperature coefficient α of the solution was examined using Kindaly 3E (manufactured by Fuso Pharmaceutical Co., Ltd.) as the agent A. Kindary 3E is a powdered dry medicine in which the electrolyte and non-electrolyte components contained in the A liquid of the dialysate are combined into one agent.

A stock solution having a correct concentration, that is, a predetermined value (188.9 mS / cm) of electrical conductivity at a reference temperature (25 ° C. in this example) was prepared. The temperature of this A stock solution was changed in increments of 1 ° C. within a range of 5 ° C. to 40 ° C., and the electrical conductivity was measured without performing temperature compensation at each temperature. The temperature coefficient at each temperature when the reference temperature was 25 ° C. was calculated from the above equation 1. That is, in the above formula 1, T is 25 [° C.], t is the temperature of the solution [° C.] (in increments of 1 ° C. in the range of 5 ° C. to 35 ° C.), and k _T (k ₂₅ ) is 188.9 [mS / cm ], Kt were substituted as electric conductivity [mS / cm] at t ° C., and a temperature coefficient α at each temperature t was calculated.

As a result of investigating the relationship between the temperature coefficient α obtained as described above and the temperature t of the solution, the relationship is expressed by the following formula 2,
α = at ² + bt + c (2)
(Where α is the temperature coefficient of the solution [%], t is the temperature of the solution [° C.], a, b, and c are regression constants)
It was found that it can be expressed by a quadratic regression equation shown in FIG.

  Next, using Kinderry 2E (manufactured by Fuso Yakuhin Kogyo Co., Ltd.), Rinpack TA-1 (manufactured by Nipro Pharma Corporation), Rinpac TA-3 (manufactured by Nipro Pharma Corporation) as the A agent, the temperature coefficient α The temperature dependence was investigated. All of Kindary 2E, Rinpac TA-1, and Rinpac TA-3 are powdered dry drugs in which the electrolyte and non-electrolyte components contained in the liquid A of the dialysate are combined. Also for these agents A, it was found that the relationship between the temperature coefficient α and the temperature t of the solution can be expressed by a quadratic regression equation represented by the above equation 2.

  FIG. 2 shows a quadratic regression curve representing the relationship between the temperature coefficient α determined for each agent A and the temperature t of the solution. Table 1 shows the regression constants a, b, and c of the quadratic regression equation obtained for each agent A.

  In addition, the regression constants a, b, and c shown in Table 1 are obtained using the average value of the temperature coefficient α at each temperature obtained by a plurality of (four) measurements.

  At this time, with respect to the regression constants a, b, and c obtained by using the average value of the temperature coefficient α at each temperature obtained by the above-described multiple times (four times), at each temperature obtained by each measurement. When the deviations of the obtained regression constants a, b, and c obtained by using the temperature coefficient α are examined, the constant a is within ± 18%, the constant b is within ± 6%, and the constant c is within ± 0.005%. Met.

  FIG. 3 shows a relationship between the temperature coefficient α and the temperature t in each of a plurality of measurements, and the average value of the temperature coefficient α and the temperature t in a plurality of measurements. The relationship is shown. Similar results were obtained when other agents A were used.

  In addition, as a result of the experimental studies by the present inventors, for any type of agent A, if the deviation from the regression constant shown in Table 1 is within a predetermined range, the converted value of the electrical conductivity is a desired error. It was found to be within the range. That is, if the deviation is within ± 25% for constant a, within ± 6.0% for constant b, and within ± 0.3% for constant c with respect to the values shown in Table 1, the electrical conductivity The converted value falls within ± 0.5 mS / cm. This is, for example, acceptable accuracy when preparing dialysate (or dialysate stock solution).

  In FIG. 4, as a representative example, when using the kindery 3E, a quadratic regression curve (reference) using the regression constants a, b, and c shown in Table 1 and regression constants a, b, and b shown in Table 1 are used. A quadratic regression curve (plus error, minus error) using regression constants a, b, and c with deviations of ± 25%, ± 6.0%, and ± 0.3%, respectively, is shown.

  Next, when the temperature coefficient α is a fixed value and when the temperature coefficient α is variable according to the temperature t using the relationship between the temperature coefficient α and the temperature t of the solution, the temperature of the measured value of electrical conductivity The accuracy of compensation was studied.

  Here, as a representative example, for the case of using Kindery 3E, the converted value of electrical conductivity when the temperature coefficient α is variable according to the quadratic regression equation using the regression constants a, b, and c shown in Table 1. Table 2 and FIG. 5 show the change of the electrical conductivity when the temperature coefficient α is fixed at 2.00% and the conversion value of the electrical conductivity according to the temperature of the solution.

  As can be seen from Table 2 and FIG. 5, by making the temperature coefficient α variable by a quadratic regression equation using the regression constants shown in Table 1, the electrical conductivity can be accurately measured over a wide temperature range of 5 ° C. to 40 ° C. Temperature compensation can be performed. On the other hand, when a fixed value of the temperature coefficient α = 2.00% is used, a temperature range of about 10 ° C. to 26 ° C. (the temperature coefficient α when variable in this temperature range is also about 2.00%. In this case, the temperature compensation is performed with relatively high accuracy, but the temperature compensation accuracy of the electrical conductivity is lowered in a temperature range lower than that and in a temperature range higher than that. Similar results were obtained when other agents A were used.

  As described above, the relationship between the temperature coefficient α and the solution temperature t is obtained in advance for each type of agent A. When measuring the electrical conductivity of the actual solution, the temperature coefficient α at the temperature t of the solution is obtained based on the relationship. And the measured value of the electrical conductivity meter 24 can be converted into the electrical conductivity in reference temperature using this temperature coefficient (alpha). In particular, in this embodiment, the relationship between the temperature coefficient α and the solution temperature t is expressed as a quadratic regression equation of the temperature coefficient α with the solution temperature t as a variable.

  More specifically, in this embodiment, the storage unit 32 of the control unit 30 stores the regression constants a, b, c for each type of agent A as information indicating the relationship between the temperature coefficient α and the temperature t of the solution. Is remembered.

  An operation unit 40 is connected to the controller 31 of the control unit 30. The operation unit 40 is provided with an input means 41 serving as an input key for inputting various settings to the controller 31. The operation unit 40 is provided with a display means 42 such as an LCD panel on which setting information is displayed. The operator can select the type of agent A to be used by the input means 41. At this time, the display on the display means 42 enables the operator to check the set items.

  When the type of agent A is selected by the input means 41, a signal designating the type of agent A is input to the controller 31. The controller 31 selects and reads the regression constants a, b, c associated with the type of agent A and stored in the storage means 32 in accordance with the input signal specifying the type of agent A. And at the time of a chemical | medical agent melt | dissolution process, the controller 31 makes the measured value of the electrical conductivity meter 24 into reference temperature (25 degreeC in a present Example) by the quadratic regression equation of the said Formula 2 using the regression constant a, b, c. ) And convert to the electrical conductivity value in

  As described above, according to the present embodiment, the electric conductivity can be accurately measured according to the type of the solute (agent A in the present embodiment) in a wide temperature range without providing the heating means to keep the temperature of the solution constant. The measured value can be temperature compensated.

Example 2
Next, another embodiment of the present invention will be described.

[Overall configuration of drug dissolving device]
FIG. 6 shows a schematic configuration of the drug dissolving device 2 of the present embodiment. In the present embodiment, the drug dissolving device 2 can be suitably used as a dry drug dissolving device for hemodialysis for preparing a dialysate solution A (or A stock solution that is a concentrated solution of agent A).

  In Example 1, the case where the A solution (or A stock solution) was prepared from the A agent in which the electrolyte component and the non-electrolyte component were combined into one agent was described. On the other hand, in the present embodiment, the drug dissolving device 2 dissolves the A agent composed of the A-1 agent that is the electrolyte component and the A-2 agent that is the glucose (non-electrolyte) component to dissolve the A solution ( Or A stock solution). In addition, the same code | symbol is attached | subjected to the element which is the same as that of the chemical | medical agent dissolution apparatus 1 of Example 1 shown in FIG. 1, or it corresponds, and detailed description is abbreviate | omitted.

  As shown in FIG. 6, the drug dissolving device 2 has a dissolving tank 15. The drug dissolution apparatus 2 includes a first hopper 11 as a drug storage unit that stores A-1 agent (powdered drug for electrolyte excluding glucose (glucose) in A agent) 101 as a dry drug, And a second hopper 12 serving as a medicine storage means that stores the medicine A-2 agent (a powdered medicine for glucose (non-electrolyte) in the agent A) 102. The first and second hoppers 11 and 12 are connected to the dissolution tank 15 via a first supply device 13 and a second supply device 14 as solute supply means, respectively.

  The inlet pipe 16 is provided with a thermometer 26 that detects the temperature of the R / O water that is the solvent. Thereby, the temperature of the solution in the dissolution tank 15 can be detected as a result. The detection signal of the thermometer 26 is input to the controller 31 through predetermined signal processing such as amplification and A / D conversion in the control unit 30.

  When preparing the A liquid (or A stock solution) of the dialysate with the drug dissolving device 2 of the present embodiment, first, the inlet valve 17 is opened with the annular flow path valve 22 and the supply path valve 23 closed. R / O water is introduced into the dissolution tank 15 through the inlet pipe 16. The amount of water is measured by a float switch 25 as a measuring means provided in the dissolution tank 15. When the amount of water is metered, the inlet valve 17 is closed, the ring passage valve 22 is opened, and the pump 19 is operated with the supply passage valve 23 closed. Thereby, the water in the dissolution tank 15 is circulated through the outlet line 18 and the reflux line 20 and stirred.

  Subsequently, the A-1 agent 101 is continuously supplied from the first hopper 11 into the dissolution tank 15 via the first supply device 13. The A-1 agent 101 is an electrolyte component mainly composed of sodium chloride excluding glucose in the A agent of the dialysate, and contains sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, and glacial acetic acid in a predetermined ratio. It is a powdered drug.

  The A-1 agent 101 is stirred and mixed in the dissolution tank 15 by circulating water. At this time, the electrical conductivity meter 24 installed in the reflux conduit 20 detects the electrical conductivity of the liquid flowing in the reflux conduit 20. By detecting this electrical conductivity, the A-1 agent concentration of the A-1 agent solution is measured based on the relationship (calibration curve) between the electrical conductivity of the A-1 agent solution and the concentration of the A-1 agent. can do.

  In this embodiment, the detection signal of the electric conductivity meter 24 is input to the controller 31 through predetermined signal processing such as amplification and A / D conversion in the control unit 30. The storage means 32 of the control unit 30 stores the electrical conductivity for the A-1 agent solution determined in advance based on the relationship (calibration curve) between the electrical conductivity of the A-1 agent solution and the concentration of the A-1 agent 101. The target value of the detection value of the rate meter 24 is stored. The controller 31 controls the first supply device 13 to appropriately supply the A-1 agent 101, and compares the detected value of the electric conductivity meter 24 with the target value, and the detected value has reached the target value. The supply of the A-1 agent 101 by the 1st supply apparatus 13 is stopped at the time of detecting. Thereby, the A-1 agent solution containing the A-1 agent 101 having a predetermined concentration is prepared.

  When the A-1 agent solution having a predetermined concentration is prepared in the dissolution tank 15, the A-2 agent 102 is then transferred from the second hopper 12 to the second supply device under stirring by the flow of the A-1 agent solution. 14 is supplied to the dissolution tank 15 by a predetermined amount. The A-2 agent 102 is a powdery drug for glucose (non-electrolyte) in the A agent of the dialysate. The A-1 agent solution and the A-2 agent 102 in the dissolution tank 15 are sufficiently agitated by being circulated and flowed through the reflux line 20 by the pump 19, and the A-1 agent solution is added to the A-2 agent solution. It becomes a mixed solution in which the agent 102 is dissolved. At this time, the electrical conductivity 24 installed in the reflux conduit 20 detects the electrical conductivity of the liquid flowing in the reflux conduit 20. By detecting this electrical conductivity, the A-2 agent concentration of the mixed solution can be measured based on the relationship (calibration curve) between the electrical conductivity of the mixed solution and the A-2 agent concentration.

  For example, as disclosed in Patent Document 2 described above, when a non-electrolyte is added to an electrolyte solution, the electrical conductivity of the solution decreases with a constant relationship as the amount of non-electrolyte added increases. Therefore, if a correlation (calibration curve) between the electric conductivity of the mixed solution and the concentration of the non-electrolyte is obtained in advance for a system in which the electrolyte and the non-electrolyte are the same, the non-electrolyte concentration is determined by measuring the electric conductivity of the mixed solution. The electrolyte concentration can be measured.

  In the present embodiment, the detection signal of the electric conductivity meter 24 is input to the controller 31 through predetermined signal processing such as amplification and A / D conversion in the control unit 30. The storage means 32 of the control unit 30 stores the relationship between the electric conductivity of the mixed solution and the concentration of the A-2 agent 102 (calibration curve) when the A-2 agent 102 is added to the A-1 agent solution having a predetermined concentration. The target value of the detected value of the electric conductivity meter 24 with respect to the mixed solution, which is determined in advance based on), is stored. The controller 31 controls the second supply device 14 to appropriately supply the A-2 agent 102, and compares the detected value of the electric conductivity meter 24 with the target value, and the detected value has reached the target value. Is detected, the supply of the A-2 agent 102 by the second supply device 14 is stopped. Thereby, the mixed solution containing A-2 agent 102 of predetermined concentration is prepared.

  When a mixed solution containing A-1 agent 101 and A-2 agent 102 having a predetermined concentration, that is, A solution (or A stock solution) is prepared in this way, the circulation passage valve 22 is then closed. In addition, when the feed passage valve 23 is opened, the mixed solution in the dissolution tank 15 is discharged to the feed conduit 21. This mixed solution flows through the supply pipeline 21 and is supplied to a storage tank (not shown). And as demonstrated in Example 1, A liquid (or A stock solution) in a storage tank is diluted with R / O water with B liquid (or B stock solution) in a dialysate supply apparatus or a personal dialysis machine, for example. By mixing, a predetermined concentration of dialysate is prepared.

  When the above process is completed, the feed passage valve 23 is closed and one melting operation is completed. In the next melting operation, the above-described operation is repeated.

[Temperature compensation for electrical conductivity]
Next, temperature compensation of the measured value of the electric conductivity meter 24 in the drug dissolving device 2 of the present embodiment will be described.

  Also in the present embodiment, the controller 31 as the control means designates the temperature coefficient α for temperature compensation of the measured value of the electric conductivity meter 24 according to the type of the solute (agent A in the present embodiment). Using information indicating the relationship between the temperature coefficient α and the temperature t of the solution, the temperature is changed according to the temperature t of the solution in the dissolution tank 15.

  Here, in Example 1, the agent A was composed of the electrolyte component and the non-electrolyte component, but in this example, the agent A-1 was used to prepare the solution A (or A stock solution). After being dissolved in R / O water, the A-2 agent is dissolved in the solution. That is, in this embodiment, the electric conductivity meter 24 detects the electric conductivity of the A-1 agent solution and the electric conductivity of the mixed solution in which the A-2 agent is dissolved in the A-1 agent solution.

  Therefore, in this example, for each agent A, the relationship between the temperature coefficient α and the temperature t of the solution is a mixture solution for agent A-1 and a solution in which agent A-2 is dissolved in agent A-1. I will ask you for two.

  More specifically, in the storage means 32 of the control unit 30, as information indicating the relationship between the temperature coefficient α and the temperature t of the solution, a regression constant a for the A-1 agent solution, b, c, and regression constants a, b, c for a mixed solution in which the A-2 agent is dissolved in the A-1 agent solution are stored.

  The controller 31 of the control unit 30 is connected with an operation unit 40 including an input unit 41 and a display unit 42. As in the first embodiment, the operator can select the type of agent A to be used by the input unit 41 of the operation unit 40.

  When the type of agent A is selected by the input means 41, a signal designating the type of agent A is input to the controller 31. The controller 31 selects and reads the regression constants a, b, c associated with the type of agent A and stored in the storage means 32 in accordance with the input signal specifying the type of agent A. In this embodiment, the regression constants a, b, and c for the A-1 agent solution and the regression constants a, b, and c for the mixed solution in which the A-2 agent is dissolved in the A-1 agent solution are read. And at the time of the dissolution process of A-1 agent, the controller 31 measures the measured value of the electric conductivity meter 24 by the quadratic regression equation of the above equation 2 using the regression constants a, b, c for the A-1 agent solution. Is converted into an electrical conductivity value at a reference temperature (25 ° C. in the present embodiment) and managed. In the process of dissolving the A-2 agent in the A-1 agent solution, the controller 31 uses the regression constants a, b, and c for the mixed solution in which the A-2 agent is dissolved in the A-1 agent solution. The measured value of the electric conductivity meter 24 is converted into the electric conductivity value at the reference temperature (25 ° C. in the present embodiment) and managed by the quadratic regression equation of the above equation 2.

  Here, Table 3 shows an example of regression constants for a dry drug composed of the A-1 agent in which the A agent is an electrolyte component and the A-2 agent in which the glucose (non-electrolyte) component is an agent.

  As described in Example 1, if the deviation from the regression constants shown in Table 3 is within a predetermined range as a result of the experimental study by the present inventors, the converted value of electrical conductivity is a desired value. It was found that it was within the error range. That is, if the deviation is within ± 25% for the constant a, within ± 6.0% for the constant b, and within ± 0.3% for the constant c with respect to the values shown in Table 3, the electrical conductivity The converted value falls within ± 0.5 mS / cm. This is, for example, acceptable accuracy when preparing dialysate (or dialysate stock solution).

  As described above, according to this example, even when the A agent is composed of the A-1 agent that is the electrolyte and the A-2 agent that is the non-electrolyte, the temperature of the solution is kept constant by providing the heating means. Without this, it is possible to accurately compensate the temperature measurement of the electrical conductivity in accordance with the type of solute (agent A in this embodiment) in a wide temperature range.

  As mentioned above, although this invention was demonstrated according to the specific Example, this invention is not limited to the above-mentioned embodiment.

  For example, the structure similar to the chemical | medical agent dissolution apparatus 1 of Example 1 can be used also for preparation of B liquid of the dialysate which is the aqueous solution of sodium hydrogencarbonate. In this case, B agent (sodium hydrogen carbonate), which is a dry chemical, is supplied from the hopper 11 to the dissolution tank 15 by the supply device 13 as a solute. In this case, the information indicating the relationship between the temperature coefficient α and the temperature t of the solution is obtained in advance in the same manner as described in Example 1 for the sodium hydrogen carbonate aqueous solution.

  The drug dissolving device is not limited to the one for preparing dialysate, and can be widely used for dissolving other drugs. For example, in the food industry or the pharmaceutical industry, for example, a solution in which sodium chloride or sodium carbonate is dissolved in water or another aqueous polar solvent, or a mixed solution in which a non-electrolyte such as sugar or alcohol is mixed with this electrolyte solution is used. There are many things to do. The present invention can be equally applied to such a drug dissolving apparatus for dissolving other drugs. In this case as well, information indicating the relationship between the temperature coefficient α and the solution temperature t may be obtained in advance for each drug.

  In addition, according to the present invention, it is possible to provide a special effect that the measured value of the electrical conductivity can be accurately compensated over a wide temperature range without providing a heating means for heating the dilution water or the solution itself. Can play. However, even when such a heating means is provided, according to the present invention, there is an advantage that the measured value of the electric conductivity meter can be more accurately temperature compensated according to the temperature of the solution.

  In each of the above embodiments, the operator inputs from the operation unit 40 the designation of the type of the dry medicine that is the solute, whereby the controller 31 stores the regression constant stored in the storage means 42 for each type of the dry medicine. a, b, and c were selected and used. For example, when a drug dissolution apparatus is used as a dry drug dissolution apparatus for hemodialysis, the types of dry drugs currently approved are limited. Further, the types of dry drugs that can be used in any drug dissolving apparatus without requiring a dedicated dialysis dissolving apparatus are further limited.

  Specifically, in the case where the agent A is made into one agent, there are RINPACK TA-1 and RINPACK TA-3 manufactured by Nipro Pharma, Inc., Kindery 2E and Kindery 3E manufactured by Fuso Pharmaceutical Co., Ltd. Also, in the case where the A agent is composed of the A-1 agent, which is an electrolyte component, and the A-2 agent, which is a glucose (glucose) component, Rinpac, Rinpac 3 manufactured by Nipro Pharma, Fuso Pharmaceutical Industries Ltd. These are Kindaly 2D, Kindaly 3D, manufactured by Ajinomoto Co., Ltd., and Highsolve-F.

  Therefore, by storing the regression constant in the storage means 42 in advance as described in the above embodiments for all or part of these dry drugs (such as those scheduled to be used), the operator can By simply inputting the type of the dry medicine to be used, it is possible to accurately compensate the temperature of the measured electric conductivity according to each dry medicine without performing complicated setting operations. However, the present invention is not limited to this.

  For example, as for the information indicating the relationship between the temperature coefficient α and the temperature t of the solution with respect to the newly usable dry medicine, for example, the regression constants a, b, c of the quadratic regression equations described in the above embodiments Can be input from the input means 41 of the operation unit 40 or the like. Further, this can be stored in the storage means 42. Such regression constant information may be provided by the manufacturer of the drug dissolution apparatus or may be separately obtained by the user of the drug dissolution apparatus.

  In each of the above embodiments, the relationship between the temperature coefficient α and the temperature t of the solution has been described as being expressed by a quadratic regression equation. According to the study by the present inventors, for example, when the solution is a dialysate (or dialysate stock solution), the relationship between the temperature coefficient α and the temperature t of the solution is expressed with sufficient accuracy by a quadratic regression equation. Can do. However, the present invention is not limited to this, and a regression equation of third order or higher may be used. In this case, of course, the number of regression constants corresponding to the order of the regression equation is used. However, even if the degree of the regression equation is increased, they do not have the effect of correspondingly improving accuracy, and conversely, the cost may increase due to excessive calculation processing. Therefore, it is generally preferable to use a quadratic to cubic regression equation.

  Further, from the viewpoint of accuracy of temperature compensation, the relationship between the temperature coefficient α and the temperature t of the solution is preferably expressed by the above-described curve equation (second-order or higher regression equation). That is, when more accurate temperature compensation is performed, it is preferable to obtain the relationship between the temperature coefficient α and the solution temperature t at more measurement points as the temperature range of the solution is wider. However, in some cases, the following polygonal line approximation method may be used.

  That is, in the broken line approximation method, for example, for a solution having a known concentration (that is, known electrical conductivity at a reference temperature), for example, the temperature at 10 points and the value of electrical conductivity at that temperature are obtained. And the relationship between the temperature coefficient between each temperature and temperature is expressed by a linear expression. When measuring the actual electrical conductivity, the temperature coefficient at the temperature of the solution is obtained from the above linear equation between the temperatures where the temperature of the solution falls within the range. Accordingly, in the case of the polygonal line approximation method, the number of linear equations is stored in advance for each type of solution (ie, solute). Although the accuracy is inferior to the case where the temperature coefficient α and the temperature t of the solution are expressed by a curved line equation, the temperature coefficient α can be changed according to the temperature t of the solution if desired by such a polygonal line approximation method.

It is a schematic block diagram of one Example of the chemical | medical agent melt | dissolution apparatus which concerns on this invention. It is a graph which shows the relationship between the temperature coefficient (alpha) for every kind of A agent, and the temperature t of a solution. It is a graph for demonstrating the error of the relationship between the temperature coefficient (alpha) and the temperature t of a solution. It is a graph for demonstrating the error range of the relationship between the temperature coefficient (alpha) and the temperature t of a solution. It is a graph for demonstrating the difference in the accuracy of the temperature compensation of electrical conductivity between the case where the temperature coefficient α is variable according to the temperature of the solution and the case where the temperature coefficient α is a fixed value. It is a schematic block diagram of the other Example of the chemical | medical agent melt | dissolution apparatus which concerns on this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Drug dissolving device 2 Drug dissolving device 13 1st supply apparatus (solute supply means)
14 Second supply device (solute supply means)
15 Dissolution tank 16 Inlet pipeline (solvent supply means)
18 Outlet pipeline (lead-out route)
19 Pump (liquid feeding means)
20 Circulation pipeline (circulation pathway)
21 Feeding pipeline (leading route)
22 Ring channel valve 23 Supply channel valve (opening / closing means)
24 Electric conductivity meter 30 Control unit 31 Controller (control means)
32 storage means 40 operation unit 41 input means

Claims (6)

A dissolution tank; a solvent supply means for supplying a solvent to the dissolution tank; a solute supply means for supplying a solute to the dissolution tank; a thermometer for detecting the temperature of the solution in the dissolution tank; and electric conductivity meter for detecting the electrical conductivity of the solution, the following equation 1 the measurement value before Symbol electric conductivity meter,
k _T = kt / {1 + α / 100 × (t−T)} (1)
(Where, T is the reference temperature [° C.], t is the temperature of the solution [° C.], k _T is the electrical conductivity converted into T ° C., kt is the electrical conductivity at t ° C., and α is the temperature coefficient of the solution [%]. )
And a control means for converting into electrical conductivity at a reference temperature T based on the above , and by detecting the electrical conductivity of the solution in the dissolution tank with the electrical conductivity meter, the solvent has a predetermined concentration. In a drug dissolution apparatus for preparing a solution in which the solute is dissolved,
The control means uses information indicating the relationship between the temperature coefficient α obtained in advance according to the type of the solute and the temperature t of the solution, and the temperature coefficient α corresponding to the temperature t of the solution in the dissolution tank. And the conversion is performed based on the equation 1 using a temperature coefficient α corresponding to the obtained temperature t of the solution in the dissolution tank . Furthermore, storage means for storing information indicating the relationship between the temperature coefficient α and the temperature t of the solution for each solute type, and input means for inputting a signal designating the solute type to the control means, And the control means uses information indicating a relationship between the temperature coefficient α and the temperature t of the solution stored in the storage means according to a signal designating the type of the solute from the input means, The drug dissolution apparatus according to claim 1, wherein a temperature coefficient α corresponding to a temperature t of the solution in the dissolution tank is obtained. The storage means stores, as information indicating the relationship between the temperature coefficient α and the solution temperature t, a regression constant of a quadratic or higher regression equation with the solution temperature t as a variable for each type of the solute. The control means reads the regression constant stored in the storage means according to a signal designating the type of the solute from the input means, and the dissolution tank by the regression equation using the regression constant The drug dissolution apparatus according to claim 2, wherein a temperature coefficient α corresponding to the temperature t of the solution is calculated. The control means uses a temperature coefficient α corresponding to the temperature t of the solution in the dissolving tank as a variable indicating the temperature t of the solution as information indicating the relationship between the temperature coefficient α and the temperature t of the solution. The drug dissolving apparatus according to claim 1, wherein the drug dissolving apparatus further includes an input unit that inputs the regression constant of the regression expression, calculated from the above regression equation.   5. The drug dissolution apparatus according to claim 1, wherein the solute is a dry drug for hemodialysis.   The drug dissolving apparatus according to any one of claims 1 to 5, wherein the solvent is reverse osmosis water.

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