JP4545096B2 - Urea concentration measurement system - Google Patents

Description

The present invention, in the extracorporeal blood circulation apparatus, such as a hemodialysis apparatus or a blood purification apparatus, urea concentration measurement Stop stem as the urea concentration from effluent was dialyzed in hemodialysis element quickly and accurately measured.

  BACKGROUND ART An extracorporeal blood circulation device having a blood circuit that circulates blood between a patient's body using a blood pump, in particular, a hemodialysis device and a blood purification device are widely known. For example, in hemodialysis, blood is collected from the arterial side of the patient, and purified blood after dialyzing with an external hemodialysis apparatus is returned to the vein side. At this time, the dialysate removes blood waste products such as urea, creatinine, uric acid, phosphorus and the like. Such hemodialyzers are widely put into practical use, and typical ones described in Patent Document 1, Patent Document 2, and the like are known.

  In the hemodialysis apparatus, a hemodialysis element having a dialysis membrane is used as a hemodialysis element for performing hemodialysis. From the blood sent from the artery side of the patient, the hemodialysis element is connected to the blood circuit side. Urine components and the like are removed through the dialysis membrane with the dialysate circuit, and excess water is removed, and the blood after dialysis is returned to the vein side of the patient.

  The dialysate after purifying blood as described above is discarded as dialysis drainage. However, this dialysis drainage contains waste products purified from blood, such as urea, creatinine, uric acid, phosphorus, etc., but these waste products are not quantitatively measured. Although these waste products are unnecessary for living organisms, they are valuable information including biological information.

In the aforementioned urea, blood is collected and tested as one of the indicators of dialysis. However, in such an examination, it often takes time to find out the result. Therefore, it is difficult to quickly feed back the result information to hemodialysis.
Japanese Patent Publication No.56-82 Japanese Patent Publication No. 61-25382

Therefore, in view of the above situation, the object of the present invention is to enable rapid measurement of the concentration of urea contained in dialysis drainage that has not been measured at present. the amount, which can be given as effective information for such indicators dialysis dose is to provide a urea concentration measuring Stop stem.

In order to solve the above problems, the urea concentration measuring method using a urea concentration measuring system according to the present invention, the oxidizing agent is reacted injected into urea and dialysis effluent contained in the dialysis effluent, by the reaction the resulting gas (especially nitrogen) detects a change in temperature due to heat generation caused by a change and / or the reaction pressure, Ru determined urea concentration in the dialysis effluent from the detected change. As the change to be detected, either a change in the pressure of the gas generated by the reaction or a change in the temperature due to the heat generated by the reaction is possible, and the urea concentration can be obtained based on both changes.

  In this urea concentration measurement method, a relationship between a change in the pressure of the gas or / and a change in temperature due to the heat generation and the urea concentration in the dialysis drainage is obtained in advance, and the detected change is determined based on the relationship. From this, the urea concentration in the dialysis effluent can be determined.

  Moreover, in the urea concentration measuring method, it is preferable that the mixing ratio of the dialysis drainage and the oxidizing agent injected into the dialysis drainage is a predetermined predetermined mixing ratio.

  Moreover, it is preferable to introduce | transduce a dialysis drainage into the measurement part which can be sealed, inject | pour the said oxidizing agent into this measurement part, and to obtain | require the urea concentration in a dialysis drainage.

Further, in the above urea concentration measuring method, it is possible to determine the urea concentration in the dialysis effluent during hemodialysis, it is possible to obtain a urea concentration measurement result information very quickly.

  The urea concentration in the dialysis drainage can be obtained continuously or intermittently.

  Further, in order to promote the reaction between urea contained in the dialysis drainage and the oxidizing agent injected into the dialysis drainage, the reaction is preferably carried out under ultrasonic application conditions.

  Examples of the oxidizing agent include halides such as hypochlorous acid, hypobromite, hypofluorite, and hypoiodite, peroxides such as hydrogen peroxide, and others having an oxidizing power equivalent to or higher than these. The oxidizing agent can be used. Of these, sodium hypochlorite is preferably used as the oxidizing agent.

That is, the urea concentration measurement system according to the present invention includes an oxidant injection means for injecting an oxidant that reacts with urea contained in the dialysis drainage into the dialysis drainage, and / or a change in pressure of the gas generated by the reaction It comprises a change detecting means for detecting a temperature change due to heat generated by the reaction, and a urea concentration calculating means for obtaining the urea concentration in the dialysis drainage liquid from the detected change.

  In this urea concentration measurement system, as the urea concentration calculation means, for example, the relationship between the change in the pressure of the gas or / and the change in temperature due to the heat generation and the urea concentration in the dialysis effluent is obtained in advance. Based on this, it can be configured as means for obtaining the urea concentration in the dialysis drainage.

  The oxidant injection means preferably includes means for injecting the oxidant such that the mixing ratio of the dialysis drainage and the oxidant becomes a predetermined predetermined mixture ratio.

  Moreover, the urea concentration measurement system according to the present invention has a measurement unit capable of sealing dialysis drainage, and the oxidant is injected into the dialysis drainage introduced into the measurement unit. it can. This measurement part can be made into the structure branched from the dialysis drainage line, for example.

  Moreover, it is preferable that the urea concentration measurement system according to the present invention includes an ultrasonic application unit that promotes the reaction between urea and oxidant contained in the dialysis drainage.

  Examples of the oxidizing agent include halides such as hypochlorous acid, hypobromite, hypofluorite, and hypoiodite, peroxides such as hydrogen peroxide, and others having an oxidizing power equivalent to or higher than these. The oxidizing agent is used. Of these, sodium hypochlorite is preferably used.

According to the urea concentration measurement Stop stem according to the present invention, the concentration of urea contained in the dialysis effluent, reacted by injecting an oxidizing agent, by a change or / and the reaction of the pressure of the gas generated by the reaction The change in temperature due to the generated heat is detected and measured from the detected change, so it is possible to measure extremely quickly, and it is effective for removing urea during dialysis, an indicator of dialysis amount, etc. As information, urea concentration information in the dialysis drainage can be obtained accurately and efficiently.

Hereinafter, the present invention will be described in detail together with preferred embodiments with reference to the drawings.
First, the measurement principle of the present invention will be described by taking as an example the case of using sodium hypochlorite as an oxidizing agent. The chemical reaction between (NH ₂ ) ₂ CO (urea) and NaClO (sodium hypochlorite) is as follows.
(NH ₂ ) ₂ CO + 3NaClO → N ₂ + CO ₂ + 2H ₂ O + 3NaCl
As can be seen from this reaction equation, gas (N ₂ ) is generated in the course of the reaction between urea and sodium hypochlorite. In the present invention, the urea concentration is identified by capturing the pressure change caused by the generated N ₂ . Although CO ₂ is also produced in the reaction process, it is not actually generated as a gas due to its water solubility. In the present invention, as a change to be detected, in addition to the change in the pressure of the gas generated by the reaction as described above, it is also possible to capture the change in temperature due to the heat generated by the reaction. It is also possible to determine the urea concentration. The following description will be made in the case of capturing a change in gas pressure.

In addition, as described above, as an oxidizing agent for urea,
(1) Halides such as hypochlorous acid, hypobromous acid, hypofluorous acid, hypoiodous acid, etc. (2) peroxides such as hydrogen peroxide (3) and other substances having oxidizing power.

  As an example of the concentration of the oxidizing agent, sodium hypochlorite is preferable, and effective chlorine is preferably 12% or more and free chlorine 20%, or an oxidizing agent having an oxidizing power equivalent to or higher than this. It is preferable to use a concentration of

As shown in the above chemical reaction formula, the mixing ratio of urea: oxidant is theoretically 1: 3. Actually, since the urea concentration in the dialysis drainage and the oxidizing power in the oxidant are not clear, the dialysis drainage: oxidant mixing ratio is preferably about 9: 1. For example, the urea concentration of 28 mg / dl in terms of urea nitrogen is 1.0 × 10 ⁻² M when converted to mol. When 9 ml of urea solution of this concentration is present, urea contained therein is 1.0 × 10 ⁻² × 9/1000 = 9.0 × 10 ⁻⁵ mol. On the other hand, an effective chlorine concentration of the aqueous sodium hypochlorite solution of 20% means that 200 g of Cl is contained in 1000 ml. Therefore, 1 ml contains 0.2 g of Cl. Since 0.2 g of Cl is 5.6 × 10 ⁻³ mol, 1 ml of sodium hypochlorite aqueous solution contains NaClO as a whole in an amount of 5.6 × 10 ⁻³ mol. According to the above chemical reaction formula: (NH ₂ ) ₂ CO + 3NaClO → N ₂ + CO ₂ + 2H ₂ O + 3NaCl, the number of moles of sodium hypochlorite required for the reaction is three times that of urea. As described above, Cl contained in a sodium hypochlorite aqueous solution having an effective chlorine concentration of 20% exists about 60 times that of urea and is in a sufficiently rich state. Therefore, it can be considered that 1 ml of the oxidant (sodium hypochlorite) aqueous solution is sufficient for 9 ml of dialysis drainage.

In the present invention, for example, there is a urea concentration calculating means for obtaining a urea concentration from a change in pressure of a gas obtained as a result of a reaction between a specimen (dialysis drainage) and a chemical (oxidant). When a sufficient concentration of sodium hypochlorite is present relative to the amount of urea nitrogen, the theoretical formula for the amount of gas generated is as follows:
V (ml) = 8.1 × 10 ^-3 × X × Y
V (ml): Volume of gas generated X: Urea nitrogen value (mg / dl)
Y: Aqueous urea solution (ml)

As an experimental apparatus for confirming the measurement principle, as shown in FIG. 1, a pressure change of a gas generated by a reaction in a syringe 1 containing dialysis drainage and an oxidant is measured via a trap 2 via a pressure gauge 3. The ultrasonic cleaner 4 is used as an ultrasonic application means for promoting the reaction. Specifically, the following were used for each device.
(1) Pressure gauge: MANOSTAR Puncture Pressure WO80 (mmH ₂ O)
(2) Syringe: SGE Syringes, luer lock gas tight syringe (10 ml)
(3) Ultrasonic cleaner: Yamato BRANSONIC 221
(4) NaClO aqueous solution: Disinfection stock solution made by Nipro (effective chlorine concentration: 12% or more, free chlorine concentration: 20%)

The measurement procedure was as follows.
(1) Take 9 ml of the specimen (dialysis drainage) or urea aqueous solution in the syringe.
(2) Subsequently, 1 ml of sodium hypochlorite aqueous solution is taken in the syringe. At this point, the chemical reaction begins slowly.
(3) Tighten the luer lock of the syringe, connect it to a tube ("Teflon" tube) as shown in Fig. 1, and submerge the syringe in an ultrasonic cleaner (water temperature: 37 ° C).
(4) When the ultrasonic cleaner is switched on, the chemical reaction between urea and sodium hypochlorite in the syringe is promoted, and bubbles are generated in the syringe. This time, the ultrasonic cleaner was turned on for 5 minutes, and the pressure of the gas generated in 5 minutes was measured.
(5) The generated gas is guided to the pressure gauge through the trap. In the case of a gas tight syringe, the plunger is not pushed back by the generated bubbles. Therefore, the pressure gauge pointer reflects the volume of the generated bubble as it is. The trap is installed to prevent the liquid flowing into the Teflon tube from flowing into the pressure gauge.

The results are shown in FIG. 2 as the relationship between urea concentration (mg / dl) and pressure change (mmH ₂ O). In order to confirm the reliability of the results shown in FIG. 2, the correlation between the urea concentration of the normal enzyme method and the pressure method according to the present invention was taken. As a result, as shown in FIG. It was confirmed that the urea concentration measured based on the pressure change was highly reliable. Therefore, according to the present invention, a method of reacting urea contained in dialysis drainage with an injected oxidant, detecting a change in pressure of a gas generated by the reaction, and measuring a urea concentration from the detected pressure change, It was confirmed that it was fully usable. The same can be said for the temperature change, and it is considered that the urea concentration can be similarly measured by the temperature change caused by the heat generated by the reaction.

  Examples of the system for realizing the method for measuring the urea concentration from the pressure change include embodiments as shown in FIGS. 4 and 5. The urea concentration measurement system shown in FIGS. 4 and 5 is shown as an example of a system that can be attached to the drain line of a dialysis machine and can perform substantially continuous measurement.

  In the embodiment shown in FIG. 4, a dialysis drainage introduction pipe 12 for measuring the urea concentration is provided branched from the dialysis drainage line 11. A part of the dialysis drainage introduction pipe 12 is configured in a measurement unit 15 that can be sealed in the solenoid valve 2 (13) and the solenoid valve 3 (14). An ultrasonic transducer 16 is provided as an ultrasonic application means for promoting the reaction with the oxidant, and a pressure gauge 17 as a change detection means for detecting a change in the pressure of the gas generated by the reaction is provided as a liquid removal filter 18. Connected through. An aspirator 19 is provided immediately before the measurement unit 15, and an oxidizer (sodium hypochlorite solution) injection line 21 is connected via the electromagnetic valve 1 (20).

  In FIG. 4, by opening the solenoid valve 1 (20), the ratio of the dialysis drainage and the oxidant chemical solution (sodium hypochlorite solution) by the action of the aspirator 19 (for example, a preset mixing ratio). Mixed. At this time, the reaction has started slightly. The mixed reaction liquid is guided to a sealed part (measurement unit 15) where the ultrasonic vibrator 16 is installed.

  When the solenoid valve 1 (20), the solenoid valve 2 (13), and the solenoid valve 3 (14) are simultaneously closed and the ultrasonic vibrator 16 is activated, the reaction is promoted and bubbles are generated. The generated gas is guided to the pressure gauge 17 through the liquid removal filter 18, and the change in pressure is measured. Based on the detected pressure change, the concentration of urea contained in the dialysis effluent is determined as in the measurement principle described above.

  When the pressure measurement is completed, the solenoid valve 22 (13) and the solenoid valve 3 (14) are opened, and the sealed part (measurement unit 15) is replaced with dialysis drainage not mixed with the chemical solution. Thereafter, these series of operations are repeated.

  In the embodiment shown in FIG. 5, compared with the embodiment shown in FIG. 4, an injection line 21 for the oxidizing agent (sodium hypochlorite solution) is connected to the sealed portion (measurement unit 15) via the pump 22. A certain amount of chemical solution (sodium hypochlorite solution) is injected under the control of the pump 22.

  In FIG. 5, the solenoid valve 2 (13) and the solenoid valve 3 (14) are opened, and dialysis drainage is introduced into the sealed part (measurement unit 15). At the same time when a certain amount of chemical solution (sodium hypochlorite solution) is injected by the pump 22, the solenoid valve 2 (13) and the solenoid valve 3 (14) are closed, and a certain amount of dialysis fluid and chemical solution are sealed. (Measurement unit 15) is hermetically sealed. When the ultrasonic vibrator 16 is activated, the reaction is promoted and bubbles are generated. The generated gas is guided to the pressure and pressure gauge 17 via the liquid removal filter 18, and the change in pressure is measured. Based on the detected pressure change, the concentration of urea contained in the dialysis effluent is determined as in the measurement principle described above. When the pressure measurement is completed, the solenoid valve 22 (13) and the solenoid valve 3 (14) are opened, and the sealed part (measurement unit 15) is replaced with dialysis drainage not mixed with the chemical solution. Thereafter, these series of operations are repeated.

  Although the urea concentration can be measured by the system configuration shown in FIGS. 4 and 5, the urea concentration measuring system according to the present invention can perform automatic calculation of the urea concentration. For example, the pressure gauge 17 in the system shown in FIGS. 4 and 5 is used as a pressure measuring means capable of generating a detected pressure signal, a pressure change is measured by the signal, and stored in advance based on the measured pressure change. It is possible to automatically calculate the concentration of urea contained in the dialysis drainage and output or display the calculation result in light of the relationship or the relational expression as shown in FIG. An example of the configuration of such a urea concentration measurement system is shown in FIG. In the configuration shown in FIG. 6, the dialysis drainage / chemical solution injection means 31 is controlled so that the mixing ratio of the dialysis drainage and the oxidant becomes a predetermined mixing ratio, and the pressure change due to the reaction is determined from the signal of the pressure measurement means 32. The urea concentration contained in the dialysis drainage is automatically calculated by the urea concentration calculation means 33 based on the pressure change, and the calculation result is displayed by the calculation result display means 34.

Urea concentration measurement Stop stem according to the present invention is particularly applicable to blood extracorporeal circulation apparatus, such as a hemodialysis apparatus or a blood purification device, it can also be operated in dialysis, rapid and accurate measurement of the urea concentration in the dialysis effluent become able to.

It is a schematic block diagram of the experimental apparatus for confirming the measurement principle in this invention. FIG. 3 is a relationship diagram between urea concentration and pressure change, showing the results obtained with the experimental apparatus of FIG. 1 . FIG. 3 is a correlation diagram between a urea concentration by an enzyme method and a urea concentration by a pressure method for confirming the reliability of the result of FIG. 2. It is a schematic block diagram of the urea concentration measurement system which concerns on one embodiment of this invention. It is a schematic block diagram of the urea concentration measuring system which concerns on another embodiment of this invention. It is a block diagram which shows the structural example of the urea concentration measurement system in the case of calculating urea concentration automatically in this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Syringe 2 Trap 3 Pressure gauge 4 Ultrasonic cleaner 11 as an ultrasonic application means Dialysis drainage line 12 Dialysis drainage introduction pipe 13 Electromagnetic valve 2
14 Solenoid valve 3
DESCRIPTION OF SYMBOLS 15 Measuring part 16 Ultrasonic vibrator 17 as ultrasonic application means Pressure gauge 18 as change detection means Liquid removal filter 19 Aspirator 20 Electromagnetic valve 1
21 Injection line for oxidizing agent (sodium hypochlorite solution) 22 Pump 31 Dialysate drainage, chemical solution injection means 32 Pressure measurement means 33 Urea concentration calculation means 34 Calculation result display means

Claims (8)

  Oxidant injection means that injects oxidant that reacts with urea contained in dialysis drainage into dialysis drainage, and detects changes in gas pressure caused by the reaction and / or temperature changes due to heat generated by the reaction A urea concentration measuring system comprising: a change detecting means for detecting a urea concentration in the dialysis drainage from the detected change. The urea concentration calculating means calculates the urea concentration in the dialysis drainage based on the relationship between the change in the pressure of the gas or / and the change in temperature due to the heat generation and the urea concentration in the dialysis drainage obtained in advance. The urea concentration measuring system according to claim 1 , comprising means for obtaining. The urea concentration measuring system according to claim 1 or 2 , wherein the oxidant injection means comprises means for injecting an oxidant so that a mixing ratio of dialysis drainage and oxidant becomes a predetermined predetermined mixture ratio. The urea concentration measurement system according to any one of claims 1 to 3 , further comprising a measurement unit capable of sealing the dialysis drainage, wherein the oxidizing agent is injected into the dialysis drainage introduced into the measurement unit. The urea concentration measurement system according to claim 4 , wherein the measurement unit is provided by being branched from a dialysis drainage line. The urea concentration measurement system according to any one of claims 1 to 5 , further comprising an ultrasonic application unit that promotes a reaction between urea and oxidant contained in the dialysis drainage. The urea concentration measurement system according to any one of claims 1 to 6 , wherein a halide, a peroxide, or an oxidizing agent having an oxidizing power equal to or higher than these is used as the oxidizing agent. The urea concentration measurement system according to claim 7 , wherein sodium hypochlorite is used as the oxidizing agent.

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