JP5258448B2 - Dialysis preparation - Google Patents

Description

  The present invention relates to a dialysis preparation, and more particularly to a dialysis preparation characterized by containing succinic acid and sodium organic acid as a pH regulator.

  Approximately 270,000 patients are currently receiving dialysis therapy due to chronic renal failure. This is due to the progress of hemodialysis technology and the improvement of dialysis efficiency by the improvement and development of dialyzer, but the improvement of dialysis preparations also contributes greatly.

  Currently, the most widely used dialysate in the field contains sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose, sodium bicarbonate and sodium acetate as essential components and acetic acid as a pH regulator. In general, from the standpoint of maintaining stability, agent A containing components other than sodium bicarbonate (shows acidity when dissolved in water) and agent B containing sodium bicarbonate (alkaline when dissolved in water) These two agents are dissolved in an appropriate amount of water and used as an aqueous solution at the time of use. Hereinafter, this type of dialysis solution is referred to as “acetic acid-added bicarbonate-type dialysis preparation” in the present specification.

  When using the above-mentioned “acetic acid-added bicarbonate-type dialysis preparation” as a dialysate and measuring the blood concentration of each component after treatment, only acetic acid is found to significantly exceed the standard value for healthy individuals. . That is, with respect to the reference value 0.03 to 0.1 mEq / L of a healthy person (Non-patent Document 1), by using a dialysis solution containing acetate ion 8 mEq / L, 0.62 ± 0.34 mEq / L before treatment and 1.06 ± 0.40 mEq after treatment. / L and a high value are shown (nonpatent literature 2). And because of the high blood concentration of acetic acid, the case that showed a remarkable allergic reaction (Non-patent document 3), the case that the asthma attack was reduced by using acetic acid-free dialysate (Non-patent document 4), The use of dialysate reduced from 8 mEq / L to 4 mEq / L reduces the frequency of blood pressure reduction, reduces the use of pressurizers, and lowers the dry weight in cases that appear to be acetic acid intolerance. (Non-patent document 5), the level of symptoms of acetic intolerance (itchiness during dialysis, mild breathing difficulty) was proportional to the blood acetic acid concentration (non-patent document 6), etc. ing.

  A dialysate containing almost no acetic acid has already been developed in the United States, and “Citrasate” as a concentrate and “DRYalysate” as a powder have been marketed by Advanced Renal Technology, Inc. (patent document) 1). This patent document discloses a dialysis agent in which 2.4 mEq / L of citric acid and 0.3 mEq / L of sodium acetate are added instead of acetic acid and sodium acetate, and the pH of the chemical solution corresponding to the agent A is 2.3. . Dialysis patients who cannot use heparin for dialysis due to the addition of citric acid, increased dialysis volume (non-patent document 7), increased reuse of dialyzer (non-patent document 8), compared to conventional dialysate Since blood coagulation was significantly reduced in patients with high hemorrhage, it may be applied to patients with high risk of bleeding, coagulation in the dialyzer, or patients who cannot use heparin as an anticoagulant. Reference 9).

In Japan, a similar dialysis solution was released in 2007 by Ajinomoto Co., Inc. In this dialysate, the bicarbonate ion concentration of agent B is 35 mEq / L, and citric acid and sodium citrate are added to agent A so that the total citric acid concentration is 2 mEq / L. The pH of the liquid is 7.5 to 8.0. Compared with the dialysate solution of “acetic acid-added bicarbonate-type dialysis preparation”, it was effective in correcting metabolic acidosis, but increased blood pH, decreased calcium ions, blood bicarbonate It has been reported that many adverse events such as an increase in the number of adverse events were observed (Non-patent Document 10). In addition to these, a preparation for dry dialysis used for hemodialysis using citric acid as an acid has also been reported (Patent Document 2).
Special Table 2002-527482 Patent No. 2948315 Takao Shimizu: Japanese clinical study, 57, 650 (1999) Nobuyuki Endo et al .: Artificial organs, 22 (1), 34 (1993) Mamiko Serizawa et al .: Kyushu Artificial Dialysis Society, 26, 87 (1998) Katsuyuki Takahashi et al .: Journal of Japanese Society for Dialysis Therapy, 29 (S1), 938 (1996) Junichi Onuki et al .: Journal of Japanese Society for Dialysis Therapy, 34 (S1), 903 (2001) Hiroto Hasegawa et al .: Kidney and dialysis, HDF therapy '01, 51 (other), 86 (2001) S Ahmad et al: Am J Kidney Dis, 35 (3), 493-499 (2000) S Ahmad et al: Hemodialysis International, 9, 264-267 (2005) A Tu et al: Dialysis & Transplantation, 29 (10), 620-624 (2000) Akira Saito et al .: Medical treatment and new drugs, 44 (3), 260-278 (2007)

  In each of the acetic acid-free dialysates, citric acid of about 2 mEq / L is used, but at this concentration, citric acid chelates with calcium ions, reducing the ionized Ca in the dialysate, and as a result In addition to reducing ionized Ca in the blood, the utilization rate of Ca in the living body is also reduced. Therefore, in these acetic acid-free dialysis fluids, it is necessary to increase the Ca concentration in the dialysis fluid by the amount of the reduced ionized Ca.

Moreover, when manufacturing A agent as a concentrate (for example, 30-40 times), since it is feared that a citric acid and a calcium ion couple | bond together and a calcium citrate precipitates, it needs to reduce to pH2.9 or less. Yes (Patent Document 3 and Non-Patent Document 13). However, if the pH is lowered, iron may be eluted from the agent A production or dissolution apparatus using stainless steel, which may corrode the apparatus. For this reason, the development of a new dialysis preparation that solves these problems has been awaited.
JP2003-104869 Pak CYC et al: J Endocrinol metab 65,4,801-805 (1987)

  As a result of intensive studies to solve the above-mentioned problems, the present inventors, in a dialysis preparation containing sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose and sodium bicarbonate as essential components, It has been found that these problems can be overcome by using sodium organic acid as a pH regulator.

That is, acids such as hydrochloric acid, acetic acid, lactic acid, malic acid, succinic acid, citric acid, sodium hydroxide, sodium acetate, sodium lactate, sodium malate, succinic acid that have been used in the field of injectable preparations in Japan. As a result of studies on alkalis such as sodium and sodium citrate and combinations thereof, the use of a combination of succinic acid and sodium organic acid, particularly succinic acid and sodium succinate and / or sodium citrate, As for the above, it has been found that ion ionization Ca can be suitably prevented from decreasing and that the elution of iron in the production or preparation apparatus can be suppressed by maintaining the pH of the agent A at 2.9 to 3.6. In addition, when a dialysate is prepared, released, and left to stand, there is a possibility that the pH rises due to CO ₂ release and calcium carbonate precipitates. In order to suppress this phenomenon, it has been found that, in addition to succinic acid, combined use of sodium succinate and sodium citrate is particularly effective. The present invention has been completed based on these findings.

  As is apparent from the above, the dialysis preparation of the present invention is characterized by containing succinic acid and sodium organic acid as compared with the conventional dialysis preparation. That is, the present invention is characterized in that succinic acid and sodium organic acid are used as pH regulators in a dialysis preparation containing sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose and sodium bicarbonate as essential components. To provide a preparation. Specific examples of the organic acid sodium include sodium acetate, sodium lactate, sodium malate, sodium succinate, sodium citrate, etc., but it is preferable to use sodium succinate and / or sodium citrate, particularly sodium succinate. Or a combination of sodium succinate and sodium citrate is recommended.

  The preparation for dialysis of the present invention has sodium ion of 135 to 145 mEq, potassium ion of 1.5 to 2.5 mEq, calcium ion of 2.5 to 3.5 mEq, magnesium ion of 0.5 to 1.5 mEq, chlorine ion of 105 to 115 mEq, bicarbonate ion in 1 L at the time of use. It is preferable to have a composition that can provide a dialysis solution as an aqueous solution containing 25 to 35 mEq, succinate ion 1.8 to 3.6 mEq and glucose 1.0 to 2.0 g. In use, 1L of sodium ion 135-145mEq, potassium ion 1.5-2.5mEq, calcium ion 2.5-3.5mEq, magnesium ion 0.5-1.5mEq, chlorine ion 105-115mEq, bicarbonate ion 25-35mEq, succinic acid It may have a composition that can provide a dialysis solution as an aqueous solution containing ions 1.5 to 3.1 mEq, citrate ions 0.3 to 0.5 mEq, and glucose 1.0 to 2.0 g.

  The dialysis preparation of the present invention contains sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose and sodium hydrogen carbonate, which are essential components thereof, in addition to sodium hydrogen carbonate in order to maintain stability over a long period of time. It is preferable to manufacture separately for A agent and B agent containing sodium hydrogencarbonate. At the time of use, these two agents are diluted with an appropriate amount of water and used as a dialysate. Succinic acid and sodium organic acid as pH adjusting agents are usually included in the A agent. The A agent and the B agent are usually produced as a powder or a concentrated solution, and the concentrated solution of the A agent is produced at a concentration of 30 to 40 times, particularly preferably around 35 times the concentration at the time of use.

  In addition, A-1 preparation containing sodium chloride, potassium chloride, calcium chloride and magnesium chloride, A-2 preparation containing glucose, and B preparation containing sodium bicarbonate are manufactured separately. It may be diluted with an appropriate amount of water and used as a dialysate. Also in this case, succinic acid and sodium organic acid as pH adjusting agents are usually included in the A-1 agent. A-1 agent, A-2 agent and B agent are usually produced as a powder agent or a concentrated solution, respectively, and the concentration of A-1 concentrate is 30 to 40 times, particularly preferably around 35 times the concentration at the time of use. Manufactured at a concentration.

  The dialysis preparation of the present invention is used as an aqueous solution having a pH immediately after preparation within the range of 7.2 to 7.6, particularly 7.3 to 7.5 at the time of use. In order to set it as such pH, it is preferable to contain 1.5-2.5 mEq / L of succinic acid. In addition, in order to suppress iron elution from the preparation or preparation equipment of agent A and maintain the pH of agent A at 2.9 to 3.6, sodium succinate 0.3 to 1.1 mEq / L is included. Is preferred. In addition, the said manufacturing apparatus means the apparatus used when manufacturing the concentrated liquid of A agent in a factory etc., and a preparation apparatus prepares the aqueous solution of A agent in the medical field like a hospital. Means a device used in the process, usually made of stainless steel.

  Further, in order to further suppress the precipitation of calcium carbonate in the prepared dialysate, sodium succinate and sodium citrate may be used in combination. In this case, the amount of sodium succinate added is 0 to 0.6 mEq / It is preferable to adjust the amount of L and sodium citrate added to 0.3 to 0.5 mEq / L.

  Since the preparation for dialysis of the present invention provides an acetic acid-free dialysis solution, the above-mentioned adverse effects due to the presence of acetate ions can be avoided. And the preparation for dialysis which suppresses iron elution from the manufacturing apparatus and dissolution apparatus of A agent is enabled. In addition, by adding sodium citrate, carbonic acid generated in the dialysate can be prevented without lowering the ionized Ca value in the dialysate, and hence the ionized Ca in the blood, without reducing the utilization rate of Ca in the living body. It makes it possible to provide a dialysis preparation that further suppresses calcium precipitation.

  EXAMPLES Specific examples of the present invention will be described below with reference to examples of the present invention. However, it should not be understood that the technical scope of the present invention is limited to these examples.

Example 1
Chelating action and stability of malic acid, succinic acid and citric acid In order to select an organic acid with chelating action, malic acid and succinic acid which are divalent organic acids, and citric acid which is a trivalent organic acid are used. Tested. Sodium chloride (NaCl, MW58.44, the same applies below) 63.1 g, potassium chloride (KCl, MW74.55, the same applies below) 1.49 g, calcium chloride (CaCl2 · 2H2O, MW147.01, the same applies below) 2.02 g, magnesium chloride ( MgCl2 · 6H2O, MW203.30, the same applies below) 1.02g, glucose (C6H12O6, MW180.16, the same applies below) 12.5g, sodium acetate (C2H3NaO2, MW82.03, the same applies below) 1.64g are dissolved in water and the total volume is 1000mL It was. 100 mL of this solution was taken, 134 mg of DL-malic acid (C4H6O5, MW134.09, the same applies hereinafter) was dissolved, and malic acid added 10-fold concentrated solution A was obtained. Next, take approximately 900 mL of water into a volumetric flask, dissolve 2.52 g of sodium bicarbonate (NaHCO3, MW84.01, the same applies below) and 100 mL of malic acid-added 10-fold concentrated solution A, add water to make exactly 1000 mL, The acid-added dialysate was used.

  Similarly to malic acid-added dialysate, succinic acid-added dialysate was prepared using 118 mg of succinic acid (C4H6O4, MW118.09, hereinafter the same) instead of DL-malic acid. Similarly, citric acid (C6H8O7, MW192.13, hereinafter the same) 128 mg was used to prepare a citric acid-added dialysis solution.

  When ionized Ca was measured using these dialysates as sample solutions, as shown in the table below, only the citric acid addition formulation showed a low value, and the chelating action with calcium ions was high. Further, when the stability of the dialysate was observed in a measuring flask, no precipitation was observed only in the citric acid addition formulation even after standing at room temperature for 2 days, and the stability was excellent.

Since the increase in the amount of citric acid may lower the ionized Ca value and reduce the Ca utilization rate in the living body, it is the minimum necessary amount as a stabilizer for suppressing the formation of insoluble substances in calcium carbonate in the prepared dialysate. The use of was considered possible. And since malic acid and succinic acid do not have a chelating action, it was thought that it would be better to use them as a pH adjuster for dialysate.
Table 1: Comparison of malic acid, succinic acid and citric acid added formulations

The pH is a pH meter (manufactured by Toa DK: HM-30R type), and ionized Ca is a portable blood analyzer (manufactured by i-Stat Corporation: i-STAT300F type, using an i-stat cartridge CG8 ⁺ ). It was measured by an ion selective electrode method.

Example 2
Comparison of malic acid-added and succinic acid-added prescriptions To test whether malic acid or succinic acid should be used as the pH adjuster for agent A, 110.5 g sodium chloride, 2.61 g potassium chloride, calcium chloride 3.54 g, 1.78 g of magnesium chloride and 21.9 g of glucose are weighed and dissolved in an appropriate amount of water. As pH regulators, DL-malic acid and DL-sodium malate (C4H4Na2O5 · nH2O, MW178.05 (anhydride), The same applies to Table 2 below, dissolved in the above solution, and made up to 500 mL with water. The liquid was filtered through a membrane filter having a pore diameter of 0.45 μm, and about 45 mL of the solution was dispensed into a glass screw tube and plugged to prepare several tubes. Similarly, a formulation was prepared using succinic acid and sodium succinate (C4H4Na2O4 · 6H2O, MW270.14, the same applies hereinafter) as pH regulators.

As a result of measuring the pH of the A agent concentrated solution, it was confirmed that the succinic acid-added formulation had a higher dose-response effect than the malic acid-added formulation, and the pH could be set higher.
Table 2: Comparison of malic acid-added and succinic acid-added formulations

Example 3
In order to clarify the relationship between dialysate pH and succinic acid addition amount, weighed 110.5 g sodium chloride, 2.61 g potassium chloride, 3.54 g calcium chloride, 1.78 g magnesium chloride and 21.9 g glucose. Then, it was dissolved in an appropriate amount of water, and as pH adjusters, the prescribed amounts of succinic acid and sodium organic acid in Table 3 were taken, dissolved in the above solution, and the total amount was made up to 500 mL with water. Filter the liquid through a membrane filter with a pore size of 0.45μm, and dispense approximately 45mL each into a glass screw tube, plug it, and create several concentrates for each formulation A (35 times, the same applies below). Using this, the pH of the dialysate was measured when sodium bicarbonate 30 mEq / L was mixed.

As a result, it was considered that 1.5 to 2.5 mEq / L of succinic acid was necessary to adjust the pH of the dialysate to 7.3 to 7.5, which is the same as that of blood.
Table 3: Succinic acid addition amount in succinic acid formulation

  The pH of the dialysate is about 450 mL of water in a 500 mL volumetric flask, 1.26 g of sodium hydrogen carbonate is added, dissolved by plugging, 14.3 mL of concentrated agent A is added, and finally it is accurately adjusted to 500 mL with water. The dialysis solution was mixed, and the pH was measured with a pH meter.

Example 4
Relationship between pH of concentrate A and iron elution in succinic acid addition formula To clarify the relationship between pH of concentrate A and iron elution, sodium chloride 110.5g, potassium chloride 2.61g, calcium chloride 3.54g, magnesium chloride 1.78 g and 21.9 g of glucose are weighed and dissolved in an appropriate amount of water. As pH adjusters, the prescribed amounts of succinic acid and sodium organic acid in Table 4 are taken, dissolved in the above solution, and made up to 500 mL with water. . The liquid was filtered through a membrane filter having a pore diameter of 0.45 μm, and about 45 mL of the liquid was dispensed into a glass screw tube, plugged, and several A formulations were prepared for each prescription.

  When the relationship between the pH of the A agent concentrate and the iron elution was measured, the iron elution concentration was high at 21 ppm when the iron pin was immersed in the solution for 3 days. In some cases, it was as low as 10-13 ppm. When a stainless steel washer was immersed in the solution for 20 days, similar results were shown, with the iron elution concentration being higher when the pH was about 2, and lower when the pH was 3.2 to 3.8.

Table 4: Relationship between agent A concentrate pH and iron elution in succinic acid addition formulation

  In addition, the A solution concentrated liquid immersion test takes 40 mL of the aqueous solution in a glass screw tube, one iron parallel pin (thickness 4 mm × length 20 mm, S45C carbon steel), or stainless steel washer (inner diameter 5 mm × outer diameter). One piece (16 mm × 1 mm thick, made of SUS304) was immersed, and the parallel pins were left for 3 days and the washer for 20 days at room temperature, and the iron concentration in the liquid was measured.

  The iron concentration was measured by adding 5 mL of an acetic acid / sodium acetate buffer solution for iron test and 2 mL of L-ascorbic acid solution (1 → 100) to 5 mL of the above solution, and allowing to stand for 30 minutes. Next, an ethanol (95) solution (0.25 → 50) of 2,2′-bipyridyl was added to make exactly 50 mL with water, mixed and allowed to stand for 30 minutes to obtain a sample solution. As a standard solution, 2 or 5 mL of a Japanese Pharmacopoeia standard solution (0.01 mg / mL) was used. The absorbance of the sample solution and standard solution was measured at a wavelength of 522 nm, and the iron concentration was calculated.

Example 5
Sodium succinate addition amount in succinic acid formula To clarify the relationship between A solution concentrate pH and sodium succinate addition amount, sodium chloride 110.5g, potassium chloride 2.61g, calcium chloride 3.54g, magnesium chloride 1.78g and glucose 21.9 g was weighed and dissolved in an appropriate amount of water, and the prescribed amounts of succinic acid and sodium organic acid in Table 5 were taken as pH regulators, dissolved in the above solution, and made up to 500 mL with water. The liquid was filtered through a membrane filter having a pore diameter of 0.45 μm, and about 45 mL of the liquid was dispensed into a glass screw tube, plugged, and several A formulations were prepared for each prescription. Using the sample, measure the pH of the A agent concentrate, and store the remaining 3 samples in a temperature-controlled room set at 50 ° C for 1 month, observe the change in appearance and test whether crystals precipitate. did.

  As a result, crystals did not precipitate in all formulations of the agent A concentrate pH 2.74 to 3.65. Moreover, it was thought that addition of sodium succinate 0.3 to 1.1 mEq / L was necessary to adjust the pH of the concentrated agent A to 2.9 to 3.6.

(注)Ａ剤濃縮液の安定性:セル中の数値の分子は結晶析出本数、分母は観察本数 Table 5: Sodium succinate addition in succinic acid formula

(Note) Stability of concentrated agent A: The number of numerator molecules in the cell is the number of crystal precipitates, and the denominator is the number of observations.

Example 6
Sodium citrate addition amount in succinic acid addition formulation Tested to examine the addition amount of sodium citrate as an inhibitor of calcium carbonate that may occur in the prepared dialysate.

110.5 g of sodium chloride, 2.61 g of potassium chloride, 3.54 g of calcium chloride, 1.78 g of magnesium chloride and 21.9 g of glucose are weighed and dissolved in an appropriate amount of water, and sodium citrate (C ₆ H ₅ Na ₃ O _7. 2H ₂ O, MW 294.10, the same applies below), succinic acid and sodium organic acid as specified in Table 6 were taken as specified in Table 6, dissolved in the above solution, and the total volume was made up to 500 mL with water. The liquid was filtered through a membrane filter having a pore diameter of 0.45 μm, and about 45 mL of the liquid was dispensed into a glass screw tube, plugged, and several A formulations were prepared for each prescription. Using it, A agent concentrate pH, A agent concentrate immersion test, stability of agent A concentrate, pH of dialysate when mixed with sodium bicarbonate 30mEq / L, ionized Ca of dialysate and stability of dialysate Sex was measured.

  As a result, at a sodium citrate addition amount of 1.0 mEq / L, calcium citrate precipitates when the agent A concentrate was stored at 50 ° C. for 1 month, and formulation was impossible. Without sodium citrate, the stability when dialyzed was worse than the citric acid formulation, and when mixed with air, an insoluble substance of calcium carbonate was likely to form on the dialysate surface. The stability when no citric acid was added was better than the commercially available bicarbonate-type dialysate preparation for dialysis.

  When sodium citrate was added to increase the stability of the dialysate, it was considered appropriate to add 0.3 to 0.5 mEq / L.

Table 6: Addition amount of sodium citrate in succinic acid addition formulation

  In addition, in order to observe the stability of the dialysate when mixed with dialysate and air, about 100 mL, about 75 mL and about 50 mL of the prepared dialysate were placed in a glass screw tube (total volume of 120 mL). After plugging and leaving overnight, the appearance was observed with the naked eye, and the pH was measured.

Example 7
Sodium succinate addition amount in the succinic acid addition formulation In order to examine the sodium succinate addition amount in the succinic acid addition formulation when sodium citrate 0.3 and 0.5 mEq / L were added.

  110.5g of sodium chloride, 2.61g of potassium chloride, 3.54g of calcium chloride, 1.78g of magnesium chloride, 21.9g of glucose, dissolved in an appropriate amount of water, sodium citrate as a stabilizer, succinic acid and sodium organic acid as a pH regulator Table 7 Was dissolved in the above solution, and the total amount was made up to 500 mL with water. The liquid was filtered through a membrane filter having a pore diameter of 0.45 μm, and about 45 mL of the liquid was dispensed into a glass screw tube, plugged, and several A formulations were prepared for each prescription. Using the specimen, the pH of the concentrated solution A was measured, and the remaining 3 specimens were stored in a temperature-controlled room set at 50 ° C. for one month, and the appearance was observed to test whether crystals were deposited.

  As a result, in the formulation with sodium citrate 0.5 mEq / L, crystals were precipitated at the bottom of the screw tube in the formulation of Agent A concentrated solution pH 3.69, and in the formulations with pH 3.58 or less, crystals were not precipitated. Similarly, in the sodium citrate 0.3 mEq / L addition formulation, no crystals were precipitated in all formulations of the agent A concentrate pH 2.85 to 3.65.

(注) Ａ剤濃縮液の安定性:セル中の数値の分子は結晶析出本数、分母は観察本数 From the above, it was necessary to adjust the pH of the concentrated agent A to 2.9 to 3.6, and for sodium succinate, 0 to 0.6 mEq / L had to be added.
Table 7: Addition amount of sodium succinate in succinic acid addition formula

(Note) Stability of concentrate A: The number of molecules in the cell is the number of crystal precipitates, and the denominator is the number of observations

Example 8: Preparation of powder formulation A powder formulation of formulation 39 with succinic acid 2.5 mEq / sodium succinate 0.5 mEq / L added was prepared as follows. To a mortar, 5.22 g of potassium chloride, 2.36 g of sodium succinate, 5.17 g of succinic acid, 3.56 g of magnesium chloride and 7.07 g of calcium chloride were sequentially added and mixed, and further 221.9 g of sodium chloride was added and mixed. The mixture was transferred to a flat tray, dried at 105 ° C. for 2 hours, sieved with a No. 12 sieve, placed in a vinyl bag, and mixed with 43.8 g of glucose to prepare. About 28 g of each was placed in a barrier film bag (manufactured by Toppan, layer construction OPP20 / NY15 / GL-AU12 / LLDPE50) and sealed to prepare nine bags.

  Similarly, a formulation 40 containing succinic acid 2.0 mEq / sodium citrate 0.5 mEq / L and a formulation 41 containing succinic acid 2.5 mEq / sodium citrate 0.5 mEq / L were also prepared.

（注）セルの（）内の数値: Ａ剤濃縮液を使用した場合の結果 When the solution pH and dialysis solution pH of the A formulation powders of these three formulations were tested, the results shown in Table 8 were obtained, all showing pH similar to that of the solution, and the powder was not hygroscopic and smooth. It was.
Table 8: Performance of powder preparation A with sodium citrate-succinic acid-sodium succinate added

(Note) Numbers in parentheses in the cell: Results when using the concentrate of agent A

Claims (12)

A dialysis preparation containing sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose and sodium bicarbonate as essential ingredients, including sodium chloride, potassium chloride, calcium chloride, magnesium chloride, succinic acid, sodium organic acid and glucose A preparation which is manufactured separately into an A agent containing sodium and a B agent containing sodium hydrogencarbonate, and these two agents are used together at the time of use.   The formulation according to claim 1, wherein the organic acid sodium is sodium succinate and / or sodium citrate. The preparation according to claim 1 or 2, which is prepared to contain 1.5 to 2.5 mEq of succinic acid in 1 L at the time of use. At the time of use, sodium ion 135-145 mEq, potassium ion 1.5-2.5 mEq, calcium ion 2.5-3.5 mEq, magnesium ion 0.5-1.5 mEq, chlorine ion 105-115 mEq, bicarbonate ion 25-35 mEq, succinate ion 1.8 L The preparation according to any one of claims 1 to 3, which is prepared so as to contain -3.6 mEq and 1.0-2.0 g of glucose. In use, sodium ion 135-145 mEq, potassium ion 1.5-2.5 mEq, calcium ion 2.5-3.5 mEq, magnesium ion 0.5-1.5 mEq, chlorine ion 105-115 mEq, bicarbonate ion 25-35 mEq, succinate ion 1.5 L The formulation in any one of Claims 1-3 prepared so that -3.1mEq, citrate ion 0.3-0.5mEq, and glucose 1.0-2.0g may be included. The preparation according to any one of claims 1 to 5 , wherein each of the agent A and the agent B is a powder or a concentrate. Produced separately for A-1 agent containing sodium chloride, potassium chloride, calcium chloride, magnesium chloride, succinic acid and organic acid sodium, A-2 agent containing glucose, and B agent containing sodium bicarbonate. The formulation according to any one of claims 1 to 6 , wherein these three agents are used in combination. The preparation according to any one of claims 1 to 7 , which is used as an aqueous solution having a pH immediately after preparation in the range of 7.3 to 7.5 at the time of use. The preparation according to any one of claims 1 to 8 , wherein elution of iron from a production apparatus or preparation apparatus for a dialysis preparation is suppressed. The preparation according to any one of claims 1 to 9 , wherein generation of calcium carbonate in a dialysate prepared as an aqueous solution is suppressed during use. A pH regulator used in dialysis preparations containing succinic acid and sodium organic acid, and used in dialysis preparations so as to contain 1.5 to 2.5 mEq of succinic acid in 1 liter when using the dialysis preparation. PH adjuster . The formulation according to claim 11 , wherein the organic acid sodium is sodium succinate and / or sodium citrate.