JP2001327597A - Pharmaceutical preparation for solid sodium carbonate dialysis and method for preparing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical preparation for solid sodium carbonate dialysis which eliminates the possibility of inflammation and the generation of irritating odors during a granulation process step, has high uniformity of contents, maintains a stable pH value even after long-term preservation and eliminates the possibility of decomposition and coloration of glucose. SOLUTION: This pharmaceutical preparation for solid sodium carbonate dialysis consists of two pharmaceutical preparations, an agent A containing at least >=1 electrolyte selected from the group consisting of sodium chloride, calcium chloride, magnesium chloride, potassium chloride and sodium acetate and a solid organic acid, for example, citric acid, and an agent B containing sodium carbonate. This method is for preparation of such pharmaceutical preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a solid bicarbonate dialysis preparation, that is, a two-part solid preparation for preparing a dialysate containing sodium bicarbonate.

[0002]

2. Description of the Related Art When performing hemodialysis on a patient with reduced renal function, the patient's blood is purified in an artificial kidney. The dialysate is perfused inside the artificial kidney, and waste products in the blood are generally transferred to the dialysate side through the dialysis membrane. As the dialysis solution, acetic acid dialysis solution has been widely used, but in recent years, it has been replaced by a solution using baking soda which drastically reduces discomfort during dialysis.

A dialysate containing sodium bicarbonate is usually a liquid preparation (hereinafter referred to as liquid A preparation) containing an electrolyte component (eg, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate) and a pH adjuster (eg, acetic acid). ), Liquid preparation containing sodium bicarbonate (hereinafter referred to as liquid B agent)
Are prepared from the two dialysate preparations. These dialysate preparations may contain a sugar such as glucose, or may be mixed with a separate preparation containing a sugar.

Conventionally, liquid A and liquid B have been sold in the form of a concentrated liquid prepared to a predetermined concentration, and these have been used by the user after diluting with water. However, since a single dialysis requires about 300 L of dialysate per patient, when performing dialysis treatment on a large number of patients, it is necessary to use a large amount of concentrated solution and dilute with water. Therefore, in order to reduce the burden on the person preparing the dialysate and to save space, the use of a powdered B preparation has been increasing in many cases. Along with this, a formulation for dialysis of solid sodium bicarbonate consisting of two powders of the drug A has been developed in recent years. However, in the two-part solid baking soda dialysis preparation containing glucose in the agent A, the glucose may be heated and decomposed and colored in the manufacturing process. Therefore, the time during which stability is maintained is shorter than that of a solid baking soda dialysis preparation consisting of three drugs in which glucose is separately packaged.

[0005] Powdered solid sodium bicarbonate dialysis preparations include a powdered A agent composed of an electrolyte other than baking soda, glucose and a liquid acid, and a powdered B agent composed of only sodium bicarbonate or sodium bicarbonate and sodium acetate or glucose. (Patent No. 2749)
No. 375, Japanese Patent No. 2751933 and Japanese Patent Laid-Open No. 3-38527
No.). These dialysis preparations use acetic acid, a liquid acid, as a pH adjuster. However, since acetic acid is flammable and volatile, if it is added to the inside of the granulator during the granulation process, there is a risk of ignition or irritating odor. Further, when the dialysis preparation is stored for a long period of time, the acetic acid in the preparation is volatilized, and when the dialysis solution is prepared by dissolving in water, the pH value of the dialysis solution may be higher than a set value. is there. Therefore, in consideration of the above problems, these dialysis preparations are prepared by mixing and mixing electrolytes other than baking soda and glucose with a stirring mixer, pulverizing with a pulverizer, mixing again, and forming with a dry granulator. After granulation, dry method (A) in which liquid acid is blended and mixed, and sodium chloride and glucose are mixed with a stirring mixer, and an electrolyte other than sodium chloride and sodium bicarbonate is dissolved in water in a fluidized bed granulator. After granulation while spraying the resulting aqueous solution, the agent A is manufactured by any of the fluidized bed methods (B) in which a liquid acid is blended and mixed. However, in the dialysis preparation obtained by any of the above methods (A) and (B), glucose in the obtained preparation is decomposed and colored because the heating time required for glucose during the production process is long. There is a risk.

On the other hand, solid preparations for dialysis using a solid organic acid as a pH adjuster are known (JP-A-6-335527, JP-A-6-335528, JP-A-8-92070, JP-A-8-92070). 8-92071, JP-A-8-169836, JP-A-10-
330270, JP-A-11-114054). However, these provide a one-part solid preparation for dialysis and focus on preventing the reaction between an acid and baking soda and between an electrolyte and baking soda. In addition, since these one-part solid dialysis preparations contain a large amount of baking soda, the content ratio of the pH adjuster is lower than that of the two-part dialysis solid preparation containing no baking soda. , It is difficult to keep the content uniform. Also, in the medical field where a conventional two-part dialysis solid preparation preparation apparatus for dialysis is used, when the preparation is switched to a one-part type, it is necessary to replace the apparatus with a one-part type. is there. Further, also in these solid preparations for dialysis, countermeasures regarding the decomposition and coloring of glucose described above are required.

[0007]

SUMMARY OF THE INVENTION In view of the above circumstances, the present invention is a two-part dialysis solid preparation, which has no risk of igniting or irritating odor during the granulation process, and can be stored for a long period of time. An object of the present invention is to provide a solid baking soda dialysis preparation having a stable pH value. In addition, the preparation must be free from the possibility that glucose is decomposed and colored.

[0008]

Means for Solving the Problems The present inventors have made various studies to solve the above-mentioned problems, and as a result, have used a solid organic acid as a pH adjuster contained in the agent A, and further developed a tumbling stirred fluidized bed. The present inventors have found that the intended purpose can be achieved by granulating the agent A using the granulation method, and have reached the present invention.

That is, the present invention relates to an agent A containing at least one electrolyte selected from the group consisting of sodium chloride, calcium chloride, magnesium chloride, potassium chloride and sodium acetate and a solid organic acid, and a B agent containing sodium bicarbonate.
For dialysis of solid baking soda, comprising two preparations, and a method for producing the same.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The agent A in the present invention is preferably a coating layer in which core particles containing sodium chloride contain one or more electrolytes selected from the group consisting of calcium chloride, magnesium chloride, potassium chloride and sodium acetate. It is preferable to have a structure covered by the cover. The solid organic acid may be contained in either the core particles or the coating layer, or may be contained in both. Examples of the solid organic acid include one or more acids selected from the group consisting of citric acid, oxalic acid, tartaric acid, maleic acid, ascorbic acid, oxaloacetic acid, isocitric acid and malic acid, preferably citric acid or ascorbic acid Acids are used.

The sodium chloride contained in the core particles is
Any material may be used as long as it is in a solid state and forms core particles, but is preferably in a crystalline state having a particle size of about 75 to 1,700 μm. The core particles may contain a solid organic acid in addition to sodium chloride. In producing the agent A of the present invention, the solid organic acid may be used as it is without being pulverized, or may be previously pulverized into granules having a particle size of 75 to 1,700 μm by a pulverizer or a sizing machine. Alternatively, granulation of the same size may be performed by wet or dry granulation. Further, the surface of the sodium chloride particles may be coated with a solid organic acid by a tumbling stirring fluidized bed granulation method or a fluidized bed granulation method to form granules of 75 to 1,700 μm. The core particles may further contain an electrolyte such as magnesium chloride, calcium chloride, potassium chloride, and sodium acetate. However, it is not preferable to include sodium acetate when the core particles contain a solid organic acid, since they react to generate acetic acid. Like the solid organic acids, these electrolytes may be used as they are without pulverization, or may be pulverized into granules having a particle size of 75 to 1,700 μm or granulated.

[0012] The coating layer comprises calcium chloride,
It contains one or more electrolytes selected from the group consisting of magnesium chloride, potassium chloride and sodium acetate.
As the calcium chloride, calcium chloride dihydrate, calcium chloride monohydrate, calcium chloride anhydride and the like are used. As the magnesium chloride, magnesium chloride hexahydrate is preferably used. As the sodium acetate, anhydrous sodium acetate, sodium acetate trihydrate and the like are preferably used. Further, the electrolyte contained in the coating layer,
In addition to the above components, sodium chloride may be included.
The electrolyte is dissolved in water to prepare an aqueous solution, sprayed on the core particles containing sodium chloride, and dried to form a coating layer on the core particles. The concentration of the electrolyte in the aqueous solution is preferably from 15 to 50% by weight, particularly preferably from 25 to 40% by weight. When the concentration is lower than 15% by weight, the amount of the aqueous solution increases, so that the coating time is prolonged. When the concentration is higher than 50% by weight, the electrolyte may not be completely dissolved in water to form a suspension. Further, the coating layer may include the solid organic acid. The solid organic acid is dissolved in water to prepare an aqueous solution, sprayed on core particles containing sodium chloride, and dried to form a coating layer on the core particles. The concentration of the solid organic acid in the aqueous solution is preferably from 10 to 50% by weight, particularly preferably from 20 to 45% by weight. The spraying of the aqueous solution of the solid organic acid may be performed simultaneously with, or before and after the spraying of the aqueous solution of the electrolyte. Further, the aqueous solution may contain sodium chloride or potassium chloride. However, when an electrolyte other than the above is included, the solid organic acid reacts with the electrolyte to form a salt, which is not preferable.

The agent A in the present invention can be obtained by granulation by a centrifugal fluidized-bed granulation method, a fluidized-bed granulation method, a tumbling stirred fluidized-bed granulation method, etc. A granulation method is used. In the tumbling stirred fluidized bed granulation method, a tumbling stirred fluidized bed granulation apparatus is preferably used.
The tumbling agitated fluidized bed granulator is a tumbling and fluidized bed granulating apparatus, in which the core particles are tumbled and flown by a flow action of an air flow from near the bed wall and a rolling operation by rotation of a rotor at the bottom of the apparatus, and the components in the aqueous solution Is a device for spraying and coating. The air flow rate of the air stream is preferably 0.2 to 300 m ³ / min, particularly 0.5 to 300 m ³ / min.
200 m ³ / min is preferred. If the air volume is less than 0.2 m ³ / min, the core particles tend to aggregate. On the other hand, if it is more than 300 m ³ / min, the components in the aqueous solution are liable to cause a spray-drying phenomenon, and furthermore, the impact on each particle increases, so that fine powder is liable to be generated. The rotation speed of the rotor is 20 to 1,
000 rpm is preferred, and 50 to 500 rpm is particularly preferred. If the rotation speed is lower than 20 rpm, the thickness of the coating layer becomes non-uniform, and if it is higher than 1,000 rpm, the coating layer may be scraped due to collision of coated particles and friction with the inner wall of the apparatus. Drying is performed continuously during the spraying at an exhaust temperature of 25 to 70 ° C, preferably 30 to 50 ° C. The moisture content of the dried granules is preferably from 0 to 10%.

The agent A of the present invention may contain glucose in the core particles or the coating layer, but it is more preferable that the coating layer contains glucose. The glucose has a particle size of 45 to 1,700 μm,
Is preferably ground into granules. Also, sugar components other than glucose, such as maltose, xylitol,
Trehalose and the like may be added as necessary. When glucose is contained in the core particles, the A agent is preferably granulated by a tumbling fluidized bed granulation method.
When granulation is performed by another granulation method, for example, a centrifugal fluidized bed granulation method or a fluidized bed granulation method, glucose in the obtained A agent may be decomposed and colored. When glucose is contained in the coating layer, the granulation method of the A agent is not particularly limited, and granulation can be performed by a conventional method. However, the glucose is contained in the core particles in the coating layer in a powder state. Preferably, it is mixed during the step of spraying an aqueous solution of the compound. The mixing time is between 10 and
Preferably after spraying 90%, more preferably 50-90%
After spraying. If the amount of the aqueous solution is less than 10%, and the mixture is mixed at the beginning of coating, the coloring or decomposition of glucose due to heat is likely to occur. A
The content of the agent may not be uniform. After mixing the glucose, spray the remaining 90-10% of the aqueous solution again,
Dry to complete the coating layer. A of the present invention
By adding glucose to the agent by the above method, the heating time required for glucose during the manufacturing process can be shortened, and there is no possibility that the glucose in the obtained A agent is decomposed and colored.

[0015] The sodium acetate of the agent A of the present invention need not be dissolved in water, prepared in an aqueous solution and used for coating. A part of the sodium acetate is mixed with glucose powder during the coating process. May be. In this case, the particle size of the sodium acetate powder is about 45-1,700 μm
Is preferred. By using a part of the sodium acetate in a powder state, the amount of the aqueous solution to be coated is reduced, and the time required for coating can be reduced.
Specifically, it is preferable to use 90% or less of the total amount of the sodium acetate in a powder state, more preferably 80% or less, and further preferably 70% or less. If the amount of sodium acetate used in a powder state exceeds 90%, the amount of the aqueous solution to be coated is too small, a uniform coating layer is not formed, and the content of the obtained solid sodium bicarbonate dialysis preparation is not uniform. There is a risk.

The agent B in the present invention is a preparation containing baking soda. The sodium bicarbonate may be used as it is without being pulverized in producing the agent B of the present invention, or may have a particle size of 75 to 1,700 μm, preferably 35 μm by a pulverizer or a sizing machine in advance.
It may be pulverized into granules having a size of 5 to 1,700 μm, or may be granulated by wet or dry granulation into granules of a similar size. The agent B may contain one or more electrolytes selected from the group consisting of sodium chloride, potassium chloride, and sodium acetate, in addition to baking soda. In producing the agent B of the present invention, the electrolyte may be used as it is without pulverization, or may be used in advance by a pulverizer or a sizing machine.
It may be pulverized into granules having a size of 75 to 1,700 μm, or may be granulated by wet or dry granulation into granules of a similar size. Further, the mixture is uniformly mixed with a baking soda in a mixer such as a vertical granulator, and the mixture is granulated with a dry granulator such as a roller compactor, or a fluidized bed granulator, a tumbling stirred fluidized bed granulator, or the like. May be granulated. Also,
The agent B may contain glucose. It is preferable that the glucose is previously pulverized by a pulverizer into granules having a particle size of 45 to 1,700 μm. Further, sugar components other than glucose, for example, maltose, xylitol, trehalose and the like may be added as necessary.

The solid baking soda dialysis preparation of the present invention comprises two preparations, the above-mentioned preparations A and B. The two preparations are mixed at a predetermined mixing ratio and then dissolved in water to prepare a dialysate. . Alternatively, after dissolving the agent A and the agent B in water to prepare two aqueous solutions, both may be mixed to prepare a dialysate. Alternatively, after preparing the aqueous solution by dissolving the agent A or the agent B in water, the remaining preparation may be dissolved to prepare a dialysate.

When the solid baking soda dialysis preparation of the present invention is dissolved in water to prepare a dialysate, the dialysate has, for example, the following composition. Na ⁺ 120 to 150 mEq / L K ⁺ 0.5 to 3 mEq / L Ca ²⁺ 1.5 to 4.5 mEq / L Mg ²⁺ 0.1 to 2.0 mEq / L Cl ^- 90 to 135 mEq ^{_{/ L CH 3 COO - 5~15 mEq}} / L solid organic acid ^{_{1~10 mEq / L HCO 3 - 20~35}} mEq / L glucose 0.5 to 2.5 g / L dialysate having the above composition, pH Preferably the value is between 7.2 and 7.4.

[0019]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 Potassium chloride 36.6 g, magnesium chloride hexahydrate 25.0 g, calcium chloride dihydrate 45.
An aqueous solution was prepared by dissolving 1 g and 110.8 g of anhydrous sodium acetate in 519.9 g of purified water. To a tumbling agitated fluidized bed granulator (Multiplex MP-01, manufactured by Powrex), 1,500 g of sodium chloride having an average particle diameter of 300 μm and 47.2 g of anhydrous citric acid having an average particle diameter of 300 μm were charged as core particles, and supplied with air. At a temperature of 80 ° C, the rotor rotation speed is 300 rpm and the supply air volume is 40
Under the condition of m ³ / hr, the aqueous solution was sprayed and dried at the same time. Twenty minutes later, when coating about 50% of the aqueous solution, 245.6 g of glucose powder having an average particle size of 180 μm
Into the granulator, and subsequently spraying the remaining about 50% aqueous solution sprayed in the above step, the average particle size 850μ
Agent A having m was obtained. Separately, sodium bicarbonate 3,0 with an average particle size of 100 μm
00g was charged into a roller compactor (TF-MINI, manufactured by Freund Sangyo Co., Ltd.), and a particle size of 300 to
1,700 μm agent B was obtained. Next, the measurement of the content of the agent A, the evaluation of the content uniformity, the stability test, the pH value measurement and the stability test of the dialysate prepared from the agent A and the agent B were performed. The test results are shown below.

Example 2 The same operation as in Example 1 was carried out except that the addition time of the glucose powder was changed to the time when about 80% of the aqueous solution was coated, to obtain Agent A having an average particle size of 900 μm. Was. Separately, sodium bicarbonate having an average particle size of 100 μm was used as the B agent. Next, the same test as in Example 1 was performed. The results are shown below.

Example 3 1,477 g of sodium chloride having an average particle size of 300 μm was charged into a tumbling stirred fluidized bed granulator (Multiplex MP-01, manufactured by Powrex).
At an air supply temperature of 55 ° C., 47.2 g of anhydrous citric acid and 110 g of purified water under the conditions of a rotor rotation speed of 300 rpm and an air supply volume of 40 m ³ / hr
An aqueous solution dissolved in was sprayed and dried at the same time to form core particles having an average particle size of 300 μm. Potassium chloride 3
An aqueous solution was prepared by dissolving 6.6 g, 25.0 g of magnesium chloride hexahydrate, 45.1 g of calcium chloride dihydrate and 110.8 g of anhydrous sodium acetate in 519.9 g of purified water. The above core particles were charged into a tumbling stirred fluidized-bed granulator (Multiplex MP-01, manufactured by Powrex), and at an air supply temperature of 80 ° C,
The aqueous solution was sprayed and dried under the conditions of a rotor rotation speed of 300 rpm and a supply air flow rate of 40 m ³ / hr. Thirty minutes later, when about 70% of the aqueous solution was coated, 245.6 g of glucose powder having an average particle size of 180 μm was charged into the granulating apparatus, and the remaining about 30 parts sprayed in the above step were subsequently sprayed.
% Aqueous solution was sprayed to obtain Agent A having an average particle size of 850 μm. On the other hand, the average particle size
2223.9 g of baking soda having 80 μm and 88.5 g of sodium chloride having an average particle diameter of 80 μm were charged into a vertical granulator (FM-VG25, manufactured by Powrex), and the conditions were set at 240 rpm for a blade and 3,000 rpm for a cross screw.
Mix for 10 minutes. The granules obtained by the mixing are subjected to a roller compactor (TF-MINI, manufactured by Freund Corporation).
And a B agent having a particle size of 300 to 1,700 μm was obtained by dry granulation. Next, the same test as in Example 1 was performed. The results are shown below.

Example 4 1,400 g of sodium chloride having an average particle size of 300 μm and anhydrous citric acid having an average particle size of 300 μm were used as core particles in a tumbling stirred fluidized bed granulator (Multiplex MP-01, manufactured by Powrex). 47.2 g, at an air supply temperature of 80 ° C, a rotor rotation speed of 300 rpm and an air supply volume of 40
Under m ³ / hr conditions, sodium chloride 100.0 g purified water 239 g
An aqueous solution dissolved in was sprayed and dried at the same time to form core particles having an average particle size of 300 μm. Potassium chloride 3
6.6 g, 25.0 g of magnesium chloride hexahydrate, 45.1 g of calcium chloride dihydrate and 87.8 g of anhydrous sodium acetate were dissolved in 464.8 g of purified water to prepare an aqueous solution. The above core particles were put into a tumbling agitated fluidized bed granulator (Multiplex MP-01, manufactured by Powrex), at a supply air temperature of 80 ° C., a rotor rotation speed of 300 rpm, and a supply air volume of 40 m ³ / hr. Then, the aqueous solution was sprayed and dried at the same time. After 35 minutes, when about 90% of the aqueous solution was coated, 245.6 g of glucose powder having an average particle size of 180 μm was charged into the granulator, and about 10% of the remaining about 10% sprayed in the above step was subsequently sprayed.
% Aqueous solution was sprayed to obtain Agent A having an average particle size of 900 μm. On the other hand, the average particle size
2223.9 g of baking soda having 80 μm and 88.5 g of anhydrous sodium acetate having an average particle size of 80 μm were charged into a vertical granulator (FM-VG25, manufactured by Powrex),
The mixture was mixed for 10 minutes under the conditions of a blade of 240 rpm and a cross screw of 3,000 rpm. The granules obtained by the mixing were introduced into a roller compactor (TF-MINI, manufactured by Freund Corporation) to obtain a B agent having a particle size of 300 to 1,700 μm by a dry granulation method. Next, the same test as in Example 1 was performed. The results are shown below.

Example 5 36.6 g of potassium chloride, 25.0 g of magnesium chloride hexahydrate, and 45.4 g of calcium chloride dihydrate
An aqueous solution was prepared by dissolving 1 g and 80.6 g of anhydrous sodium acetate in 447.6 g of purified water. Rolling agitated fluidized bed granulator (Multiplex MP-01, manufactured by Powrex)
In addition, 1,500 g of sodium chloride having an average particle size of 300 μm as core particles and anhydrous citric acid 4 having an average particle size of 300 μm
Charge 7.2g, at 80 ° C air supply temperature, 300r rotor speed
The aqueous solution was sprayed and dried at pm and a supply air flow rate of 40 m ³ / hr. After 30 minutes, about 90
At the time of coating, 245.6 g of glucose powder having an average particle size of 180 μm and 30.2 g of anhydrous sodium acetate powder having an average particle size of 150 μm were charged into the granulator,
Subsequently, the remaining about 10% aqueous solution sprayed in the above step was sprayed to obtain Agent A having an average particle size of 900 μm. Also,
Separately, sodium bicarbonate having an average particle size of 100 μm was used as the B agent. Next, the same test as in Example 1 was performed. The results are shown below.

Comparative Example 1 Potassium chloride 36.6 g, magnesium chloride hexahydrate 25.0 g, calcium chloride dihydrate 45.
An aqueous solution was prepared by dissolving 1 g and 110.8 g of anhydrous sodium acetate in 519.9 g of purified water. Rolling agitated fluidized bed granulator (Multiplex MP-01, manufactured by Powrex)
In addition, sodium chloride core particles having an average particle size of 300 μm 1,50
0g, at an air supply temperature of 80 ° C, rotor speed 300rpm
The aqueous solution was sprayed and dried at the same time and under a supply air flow rate of 40 m ³ / hr. After 30 minutes, about 80% of the aqueous solution
At the time of coating, 245.6 g of glucose powder having an average particle size of 180 μm is put into the granulator, and then the remaining approximately 20% aqueous solution sprayed in the above step is sprayed to have an average particle size of 850 μm Granules were obtained. Then, 36.9 g of glacial acetic acid was added into the granulator and mixed for 10 minutes.
Agent A having an average particle size of 850 μm was obtained. On the other hand, the average particle size is 10
Roller compactor (TF)
-MINI, manufactured by Freund Corporation) to obtain a B agent having a particle size of 300 to 1,700 µm by dry granulation. Next, the same test as in Example 1 was performed. The results are shown below.

Comparative Example 2 36.6 g of potassium chloride, 25.0 g of magnesium chloride hexahydrate, and 45.4 g of calcium chloride dihydrate
An aqueous solution was prepared by dissolving 1 g and 110.8 g of anhydrous sodium acetate in 519.9 g of purified water. Rolling agitated fluidized bed granulator (Multiplex MP-01, manufactured by Powrex)
In addition, 1,500 g of sodium chloride having an average particle size of 300 μm as core particles and anhydrous citric acid 4 having an average particle size of 300 μm
Charge 7.2g, at 80 ° C air supply temperature, 300r rotor speed
The aqueous solution was sprayed and dried at pm and a supply air flow rate of 40 m ³ / hr. Forty minutes later, when the entire amount of the aqueous solution was coated, 245.6 g of glucose powder having an average particle size of 180 μm was charged into the granulator and mixed for 10 minutes to obtain Agent A having an average particle size of 850 μm. Was. On the other hand, 3,000 g of baking soda having an average particle diameter of 100 μm was charged into a roller compactor (TF-MINI, manufactured by Freund Corporation),
Agent B having a particle size of 300 to 1,700 μm was obtained by dry granulation. Next, the same test as in Example 1 was performed. The results are shown below.

[Test Results] For the preparation A of the solid baking soda dialysis preparation obtained in the above Examples 1 to 5 and Comparative Examples 1 and 2, the contents of electrolyte, citric acid and glucose were measured, the uniformity of contents was evaluated, and the stability was stable. A sex test was performed. Further, when the A agent and the B agent of the solid baking soda dialysis preparation obtained in Examples 1 to 5 and Comparative Examples 1 and 2 were dissolved in water to have a prescribed concentration to prepare a dialysis solution, The pH value of the dialysate was measured and a stability test was performed.

(Measurement of Content of Agent A, Evaluation of Uniformity) From Agent A of the preparation for solid sodium bicarbonate dialysis obtained in Examples 1 to 5 and Comparative Examples 1 and 2, 50 g was arbitrarily sampled six times. Was dissolved in water to prepare a 500 ml aqueous solution. The content of each component in the aqueous solution was measured, and the ratio (%) of the average value of the measured content to the theoretical value and the CV value (%) (coefficient of variation) are shown in Table 1. Na and K were measured with a flame photometer, Ca and Mg were measured with an ion chromatograph, acetate ion (AcO ⁻ ) and citric acid were measured with a HPLC-UV, Cl was measured with a silver nitrate titration method, and glucose was measured with a polarimeter.

[0029]

[Table 1] Upper number: (mean value of measured content) / (theoretical value) × 10
0 (%) In parentheses at the bottom: CV value (%)

As is evident from Table 1, all of the A agents in the solid baking soda dialysis preparation of the present invention have an average value of each component content close to the theoretical value, a small CV value, and show excellent content uniformity. You can see that On the other hand, Agent A of the preparation for dialysis of solid baking soda obtained using acetic acid as the pH adjuster of Comparative Example 1 had a considerably non-uniform content of acetate ions. Comparative Example 2
The aqueous solution of the compound contained in the coating layer in the core particles of the above, the agent A of the solid baking soda dialysis preparation obtained by adding glucose powder after the coating step was completed, the glucose content was non-uniform .

(Stability test of Agent A) Agent A of the solid sodium bicarbonate dialysis preparation obtained in Examples 1 to 5 and Comparative Examples 1 and 2
Enclose 50g in 100x100mm aluminum packaging material, (A) 25 ℃, 6
For products stored at 0% RH for 6 months or (B) at 40 ° C and 75% RH for 3 months, coloration of Agent A in the bag was measured using a color difference meter (Z-30
0A, manufactured by Nippon Denshoku Co., Ltd.). Table 2 shows the results.

[0032]

[Table 2]

As is clear from Table 2, the coloring agent A of the preparation for dialysis of solid sodium bicarbonate of the present invention did not show any coloration even after long-term storage. On the other hand, Agent A of the solid sodium bicarbonate dialysis preparation obtained using acetic acid as the pH adjuster of Comparative Example 1 was colored after storage.

(Measurement of pH value of dialysate and stability test)
Agents A and B of the solid baking soda dialysis preparations obtained in Examples 1 to 5 and Comparative Examples 1 and 2 were dissolved in water according to the formulation shown in Table 3 to prepare a 2,000 ml aqueous solution. And The pH value of the dialysate was measured with a pH meter (F14, manufactured by Horiba, Ltd.). Table 3 shows the results. Also,
50 g of the A agent and the B agent of the solid baking soda dialysis preparation obtained in the above Examples 1 to 5 and Comparative Examples 1 and 2 were each 100 ×
Enclosed in 100mm aluminum packaging material, (A) 6 at 25 ° C, 60% RH
For 3 months at 40 ° C., 75% RH. Agent A and Agent B in the bag were dissolved in water according to the formulation shown in Table 3 to prepare a 2,000 ml aqueous solution, which was used as a dialysate.
The pH value of the dialysate was measured with a pH meter (F14, manufactured by Horiba, Ltd.). Table 3 shows the results.

[0035]

[Table 3]

As is clear from Table 3, all dialysates prepared from the solid baking soda dialysis preparation of the present invention have a preferable pH of 7.2 to 7.4 as a dialysate, and even after long-term storage, the dialysate has a pH of 7.2 to 7.4. No increase in pH value was seen. On the other hand, the dialysate prepared from the solid sodium bicarbonate dialysis preparation obtained using acetic acid as the pH adjuster of Comparative Example 1 was dialyzed immediately after dialysate preparation due to volatilization of acetic acid during the preparation of the solid sodium bicarbonate dialysis preparation. It has an undesirably high pH value as a liquid, and the pH value further increased after long-term storage.

[0037]

The solid baking soda dialysis preparation of the present invention uses a solid organic acid as a pH adjuster to ignite or irritate odor during the granulation process like a solid baking soda dialysis preparation using acetic acid. There is no risk of occurrence. The dialysate prepared by dissolving the solid baking soda dialysis preparation in water has a preferable pH immediately after preparation, and does not increase even after long-term storage. The solid baking soda dialysis preparation of the present invention can provide a solid baking soda dialysis preparation excellent in content uniformity, preferably by using a tumbling stirred fluidized bed granulator. Furthermore, a solid baking soda dialysis preparation which is free of glucose decomposition and coloration and has a long-term storage stability can be obtained. In addition, by adding a part of sodium acetate in a powder state, the production time of the preparation for solid sodium bicarbonate dialysis can be shortened.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Makoto Sato 3-9-3 Honjo Nishi, Kita-ku, Osaka F-term in Nissha Corporation (reference) 4C077 AA05 BB01 GG09 NN18 PP21 PP24 PP29

Claims (12)

[Claims] 1. An A agent containing one or more electrolytes and a solid organic acid selected from the group consisting of sodium chloride, calcium chloride, magnesium chloride, potassium chloride and sodium acetate, and a B agent containing sodium bicarbonate. A solid baking soda dialysis preparation comprising a preparation. 2. The solid organic acid is one or more acids selected from the group consisting of citric acid, oxalic acid, tartaric acid, maleic acid, ascorbic acid, oxaloacetic acid, isocitric acid and malic acid. The preparation for dialysis of solid baking soda according to the above. 3. The agent A containing an electrolyte and a solid organic acid contains core particles containing sodium chloride and one or more electrolytes selected from the group consisting of calcium chloride, magnesium chloride, potassium chloride and sodium acetate. 3. The solid according to claim 1, comprising a coating layer, wherein the core particles are covered by the coating layer, and a solid organic acid is a preparation contained in the core particles and / or the coating layer. 4. Preparation for baking soda dialysis. 4. The agent A containing an electrolyte and a solid organic acid comprises core particles containing sodium chloride and a solid organic acid, and a coating layer containing calcium chloride, magnesium chloride, potassium chloride and sodium acetate. The preparation for dialysis of solid sodium bicarbonate according to any one of claims 1 to 3, wherein the core particle is a preparation covered with the coating layer. 5. The agent A containing an electrolyte and a solid organic acid comprises core particles containing sodium chloride and a coating layer containing calcium chloride, magnesium chloride, potassium chloride, sodium acetate and a solid organic acid. The preparation for dialysis of solid sodium bicarbonate according to any one of claims 1 to 3, wherein the core particle is a preparation covered with the coating layer. 6. The preparation according to claim 1, wherein the agent B containing sodium bicarbonate is a preparation containing one or more electrolytes selected from the group consisting of sodium chloride, potassium chloride and sodium acetate. Preparation for solid sodium bicarbonate dialysis. 7. The preparation for dialysis of solid sodium bicarbonate according to claim 1, wherein the agent A comprises glucose. 8. The formulation for dialysis of solid sodium bicarbonate according to claim 1, wherein the agent B comprises glucose. 9. A method for producing a solid baking soda dialysis preparation comprising the following steps (1) to (3). (1) a step of spraying a part of an aqueous solution containing one or more electrolytes selected from the group consisting of calcium chloride, magnesium chloride, potassium chloride and sodium acetate on core particles containing sodium chloride, and drying; A step of mixing glucose powder with the product obtained in step (1), and (3) spraying the remainder of the aqueous solution containing the electrolyte sprayed in step (1) on the mixture obtained in step (2). And drying to obtain agent A containing an electrolyte and a solid organic acid 10. In the step (1), an aqueous solution containing at least one electrolyte selected from the group consisting of calcium chloride, magnesium chloride, potassium chloride and sodium acetate is prepared using a tumbling stirred fluidized bed granulator. The method for producing a solid baking soda dialysis preparation according to claim 9, wherein the preparation is sprayed on core particles containing sodium chloride. 11. The method according to claim 9, wherein in step (1), the core particles containing sodium chloride comprise a solid organic acid.
Or the method for producing a solid baking soda dialysis preparation according to 10. 12. The method for producing a solid baking soda dialysis preparation according to any one of claims 9 to 11, which comprises a step of separately obtaining a B agent containing baking soda.