JP2987488B2 - Solid dialysis agent and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to sodium chloride,
The present invention relates to a solid dialysis agent comprising, as essential components, an electrolyte composition comprising potassium chloride, calcium chloride, magnesium chloride and sodium acetate and a pH adjuster, and glucose as an optional component, and a method for producing the same.

[0002]

2. Description of the Related Art At present, as a dialysis agent, a bicarbonate dialysis agent is mainly used. However, these agents are prepared by converting a plurality of electrolyte components into a concentrated solution of agent A and sodium bicarbonate into a powder or an aqueous solution. It consists of two agents, agent B. this house,
In the past few years, about the formulation used in the form of liquid,
Many problems due to the use of liquids have been taken up. Generally, the concentrated solution is packaged in a polyethylene container, and the agent A is usually sold in a weight of about 10 kg. The weight and volume of such a liquid dialysate are inevitably increased, and there are problems of transportation cost, storage space in a hospital, poor transportability in a hospital, and the like.

[0003] Further, in the method of discarding used packaging containers of up to 10 liters, there is a problem that even if incinerated, the volume is large and harmful gas is generated. ing.

[0004] As one of means for solving such a problem, powdering of a dialysis agent has attracted attention.

Conventionally, dry granulation and wet granulation are well-known techniques for pulverizing a dialysis agent, but both of these techniques reduce variations in components due to differences in the particle size and specific gravity of each electrolyte composition. In order to avoid this, each of the electrolyte compositions is pulverized, uniformly mixed, and then granulated to maintain the uniformity of the components. Such a production method requires complicated physical steps such as pulverization and granulation, and it can be said that the preparation is easily contaminated.

[0006] In addition, preparations using the pulverized electrolyte composition generally have high bulk and poor fluidity, and thus exhibit a high angle of repose. For these reasons, there is a problem that the packaging form is enlarged, and a large amount of preparation is supplied at once due to poor fluidity at the time of taking out the preparation. On the other hand, at the time of dissolution, there is an advantage that water is rapidly taken into the inside of the preparation, but in some cases, solidification due to water absorption progresses due to the disintegration rate of the preparation to form a solid mass, and the dissolution rate is markedly increased. There are many phenomena that lower it. In addition, powdering by spray drying is also known. However, the above-mentioned problem still remains, and research is being conducted daily to powderize dialysis agents.

[0007]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a novel method for preparing a solid dialysis preparation for preparing a bicarbonate dialysate, and to provide a bulk specific gravity, an angle of repose and a dissolution rate that are extremely high. It is good, improves workability when preparing dialysis fluid, and reduces transportation costs by reducing the packaging volume, reducing storage space in hospitals, etc.
Another object of the present invention is to provide a preparation capable of simplifying disposal of a packaging container.

[0008]

DISCLOSURE OF THE INVENTION The present invention relates to a solid dialysis system comprising an electrolyte composition of sodium chloride, potassium chloride, calcium chloride, magnesium chloride and sodium acetate and a pH adjuster as essential components, and glucose as an optional component. (1) a core layer containing at least one member selected from the group consisting of sodium chloride and potassium chloride as a main component; and (2) a double salt formed by a reaction between sodium acetate and calcium chloride, and another electrolyte composition And pH
A solid dialysis agent having a two-layer structure of a regulator and a double salt layer containing glucose as an optional component (hereinafter referred to as the first invention).
Is provided.

Further, the present invention provides a solid dialysis agent comprising an electrolyte composition comprising sodium chloride, potassium chloride, calcium chloride, magnesium chloride and sodium acetate, a pH adjuster and glucose as essential components.
A core layer (center) containing at least one member selected from the group consisting of sodium chloride and potassium chloride as a main component;
It has a three-layer structure of (2) a double salt layer (intermediate layer) containing a double salt produced by the reaction of sodium acetate and calcium chloride, another electrolyte composition and a pH adjuster; and (3) an outer layer containing glucose. The present invention provides a solid dialysis agent (hereinafter, referred to as a second invention).

Further, the present invention relates to a method of adding water to a mixture of sodium chloride, potassium chloride, magnesium chloride and sodium acetate, adding calcium chloride at an internal temperature of about 50 to 100 ° C., and adding calcium chloride. The mixture has a water content of about 20 to 300% by weight of calcium chloride, and comprises a granulation step, a sizing step, a drying step, and a step of adding and mixing a pH adjuster, and comprises sodium chloride and potassium chloride. It has a two-layer structure of a core layer containing at least one member selected from the group as a main component, a double salt formed by a reaction between sodium acetate and calcium chloride, and a double salt layer containing another electrolyte composition and a pH adjuster. An object of the present invention is to provide a method for producing a solid dialysis agent which does not contain glucose as an essential component (the production method of the first invention which does not make glucose an essential component).

[0011] Furthermore, the present invention relates to a sodium chloride,
Water is added to a mixture of potassium chloride, magnesium chloride, sodium acetate, and glucose, and calcium chloride is added under heating at an internal temperature of about 50 to 80 ° C., and the content of water in the mixture when calcium chloride is added is A mixing granulation step that is about 20 to 100% by weight of the weight of calcium chloride;
And a step of adding and mixing a pH adjuster after addition of calcium chloride, a sizing step and a drying step, a core layer containing at least one selected from the group consisting of sodium chloride and potassium chloride as a main component, sodium acetate and calcium chloride A method for producing a solid dialysis agent comprising as an essential component glucose having a double-layered structure comprising a double salt formed by the reaction of the double salt, another electrolyte composition, glucose and a double salt layer containing a pH adjuster (glucose is an essential component) (The production method of the first invention).

Further, the present invention relates to a two-layered solid dialysis agent which is a granulated product obtained by the production method of the first invention which does not contain glucose as an essential component and which does not contain a pH adjuster. The internal temperature is about 30 to 80 ° C, preferably 40 to 6
Glucose is added and mixed at a temperature of about 0 ° C, more preferably about 40 to 50 ° C, and mixed with the solid dialysis agent and water at about 0.5 to 5.0% by weight of the total weight of glucose. A core layer containing at least one selected from the group consisting of sodium chloride and potassium chloride as a main component, comprising a step of mixing and granulating, a step of adding and mixing acetic acid to the granulated substance, and a step of drying; Of a solid dialysis agent having a three-layer structure of a double salt layer containing a double salt formed by the reaction of calcium chloride with calcium chloride, another electrolyte composition and a pH adjuster, and an outer layer containing glucose (the second invention) Manufacturing method).

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION

(I) Regarding the solid dialysis agent of the first invention and the second invention The solid dialysis agent of the second invention is obtained by coating the outside of the solid dialysis agent of the first invention which does not contain glucose with an outer layer containing glucose. And may coexist with another electrolyte composition in the double salt layer, like the dialysis agent containing glucose of the first invention, and is preferably coated as an outer layer as in the second invention. .

The solid dialysis agent of the present invention can be used as a bicarbonate dialysis agent when used in combination with sodium bicarbonate.

If the solid dialysis agent of the present invention is a solid,
It may be in any state such as a powder, a granule, and a fine granule. Further, as shown in FIG. 1, the shape may be a slightly rounded cube in which one core layer (1) is included in one particle or a shape close thereto, as shown in FIG. As described above, any of the forms in which a plurality of core layers (1) are bonded to one particle via a double salt layer (2) may be used. The second
In the case of the invention, an outer layer (3) containing glucose may be present in a state surrounding the double salt layer (2) in FIG. 1 (see FIG. 3A), and the outer layer (3) may be provided outside the double salt layer in FIG. ) May be formed (FIG. 3B).

In the solid dialysis agent of the present invention, in X-ray diffraction, 2θ = about 6.8 to 7.0 ° derived from a double salt formed by the reaction between sodium acetate and calcium chloride (X-ray:
A specific peak is shown at Cuλ (Kα1) = 1.5405 Å. By forming the double salt,
In each of the electrolyte compositions not included in the core layer, the core layer is uniformly coated compositionally without any process for maintaining the uniformity of the components, for example, a process of pulverization or particle size adjustment. Has the effect of doing

The particle size of the core layer containing at least one member selected from the group consisting of sodium chloride and potassium chloride present in the solid dialysis agent as a main component is 150 to 2
It is about 000 μm, preferably about 250 to 1000 μm, and more preferably about 250 to 800 μm.

A preferable ratio of each component of the electrolyte composition is as follows:
The total amount of the electrolyte composition is shown below as 100% by weight.

Sodium chloride = about 75.9 to 94.6% by weight; potassium chloride = about 1.1 to 4.1% by weight; calcium chloride = about 1.1 to 4.0% by weight; magnesium chloride = 0. Sodium acetate = about 2.4 to 13.5% by weight.

The ratio of the pH adjuster and glucose to 100 parts by weight of the electrolyte composition is shown below.

PH adjuster = about 0.8 to 3.6 parts by weight; glucose = about 0 to 29.6 parts by weight.

The pH adjuster is not particularly limited as long as it is a pharmacologically acceptable liquid acid and solid acid, and examples thereof include liquid acids such as acetic acid and hydrochloric acid and solid acids such as citric acid and malic acid. .

The solid dialysis agent of the present invention has a bulk specific gravity of 0.1.
About 77 to 2.0 g / ml, preferably 1.0 to 1.5
g / ml. Also, the angle of repose is about 35 ° or less,
Preferably it is about 30 ° or less.

The ratio of the solid dialysis agent of the present invention to sodium bicarbonate when used as a bicarbonate dialysis agent is such that sodium bicarbonate is 23.0 to 39.0 based on 100 parts by weight of the solid dialysis agent. It is about parts by weight.

Further, the solid dialysis agent of the present invention contains silicon oxide and has a water vapor transmission rate (40 ° C., 90% RH) of 2.0 g /
By packaging in a packaging material (hereinafter, referred to as a silica-deposited film) having a size of cm ² · 24 hr or less, it became possible to obtain a preparation having excellent stability.

(II) Method for Producing Solid Dialysis Agent of the First and Second Inventions The solid dialysis agent of the first invention is obtained by adding water to a mixture of sodium chloride, potassium chloride, magnesium chloride and sodium acetate, Calcium chloride is added under heating at an internal temperature of about 50 to 100 ° C., and the mixture is granulated. The granulated product is sized and dried by a conventional method, and then a pH adjusting agent is added and mixed. You.

The water is preferably added before the time of adding calcium chloride, and may be added as an aqueous solution of calcium chloride.

The amount of water to be added depends on the water of crystallization of each electrolyte composition,
20-300 of the weight of calcium chloride, including attached water
%, Preferably about 30 to 200% by weight, more preferably about 40 to 100% by weight.

On the other hand, the solid dialysis agent of the first invention containing glucose is prepared by adding water to a mixture of sodium chloride, potassium chloride, magnesium chloride, sodium acetate and glucose, and heating the mixture to an internal temperature of about 50 to 80 ° C. Calcium chloride is added and granulated underneath, and after adding calcium chloride, a pH adjuster is added and mixed, and the granulated material is sized by a conventional method.
It is manufactured by drying.

In this case, the amount of water to be added is 2% of the weight of calcium chloride, including water of crystallization and adhesion of each electrolyte composition.
It is about 0 to 100% by weight.

After the addition of water, calcium chloride is added and mixed at a temperature of about 50 to 100 ° C. (about 50 to 80 ° C. when glucose is contained) to thereby react sodium acetate and calcium chloride. Then, the double salt layer is formed, and the granulated product is sized and dried to obtain a solid dialysis agent having a desired two-layer structure.

The double-layered solid dialysis agent containing no glucose and a pH adjuster obtained in the first invention is treated at an internal temperature of 30 to 80 ° C.
About, preferably about 40 to 60 ° C., more preferably about 40 to 50 ° C., and adding and mixing glucose under heating.
A step of mixing and granulating in the presence of about 0.5 to 5.0% by weight of water of the total weight of the solid dialysis agent and glucose, adding acetic acid to the granulated substance, mixing, and then drying. The solid dialysis agent having a three-layer structure of the second invention having an outer layer containing glucose is obtained. The amount of water is about 0.5 to 5.0% by weight, preferably 1.0 to 5.0% by weight of the total weight of the solid dialysis agent and glucose.
It is about 3.0% by weight.

The mixing ratio of each component is as described above.

[0034]

The solid dialysis agents of the first and second inventions are
Compared to powdered preparations by conventional dry or wet granulation, spray-drying, etc., the dissolution rate is significantly superior, there is no risk of caking during the dissolution process,
It has a formulation structure that dissolves in order from each layer that is the surface of the granulated material.

Further, the bulk specific gravity is extremely high and the angle of repose is good.

The product of the present invention having such characteristics significantly improves the workability in preparing a dialysis solution, and can significantly reduce the packaging volume, thereby reducing transportation costs, The storage space at the hospital can be reduced.

Furthermore, since a packaging material that can be incinerated is used, simplification of disposal can be achieved, and a packaging material having excellent glucose stability can be established because the packaging material has extremely low moisture permeability. In particular, the dialysis agent of the second invention has extremely good glucose stability.

[0038]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in more detail with reference to embodiments.

Example 1 Each raw material shown in Table 1 below was used.

[0040]

[Table 1] Sodium chloride 250.20 kg Potassium chloride 6.15 kg Calcium chloride 9.07 kg Magnesium chloride 4.27 kg Sodium acetate 20.34 kg Acetic acid 4.96 kg First, use sodium chloride having an average particle size of about 350 μm, and use potassium chloride, magnesium chloride, and sodium acetate. And 4.7 liters of pure water are put into a double can type stirring mixer (steam heating) and heated while stirring, and the temperature of the contents is reduced to 70 ° C.
And Calcium chloride was added to the mixture and mixed.

After 15 minutes from the addition of calcium chloride, the content becomes slightly whiter, and when the content is heated and mixed while maintaining the content temperature at 70 ° C., the content has specific viscosity.
The particles of the contents began to adhere to each other. Then, the contents were taken out, sized, dried, acetic acid was added and mixed, and the product was collected.

The average particle size of the obtained preparation is about 500 μm.

Regarding the structure of the preparation obtained according to Example 1,
Details are shown below.

First, FIG. 4 shows a microscope image, and the shape of the whole granulated product will be described.

It is apparent from FIG. 4 that the present preparation is a single particle having one core layer and one double salt layer, or a preparation in which a plurality of these particles are combined. On the other hand, when the cross section of one particle is observed by an electron microscope image (FIG. 5), the nucleus layer and the outer layer (double salt layer)
And the double structure is clearly shown.

Further, the preparation was prepared by the X-ray diffraction (X-ray diffraction) shown in FIG.
As shown in the line: CuKα ₁ ), there is a specific peak around 2θ = 7.0 °, excluding the peaks originating from each raw material used. This is a double salt produced by a hydrothermal reaction between sodium acetate and calcium chloride.

The components of one particle having a two-layer structure are analyzed by electron beam microanalysis (EPMA) from the particle nucleus side to the outer layer (double salt layer) on the sectional line of one particle shown in FIG. In the particle nucleus layer, only Na and Cl were detected, and in the outer layer (double salt layer), Ca, Mg, and K were detected, and the detected amounts of Cl and Na were decreased (FIG. 8). From these results, the core layer is sodium chloride, and the outer layer is a layer containing Ca, Mg, and K, that is, a double salt layer formed by a hydrothermal reaction between sodium acetate and calcium chloride. It can be seen that the electrolyte composition of the present invention is contained.

Therefore, the preparation of this example is characterized in that a core layer composed of sodium chloride, another electrolyte composition formed by the reaction of sodium acetate and calcium chloride, and a double salt layer containing acetic acid as a pH adjuster (X-ray diffraction In 2θ = 7.
One particle having a two-layer structure of around 0 ° (having a peak at X-ray: CuKα ₁ ), and the double salt formed as a binder, and a plurality of these particles are combined.

Also, five samples were randomly taken from the obtained product, and 7.161 g of each sample was obtained.
When the second formulation is a sodium bicarbonate 2.52g per liquid was accurately 1000ml dissolved in water, Na ^+,
The electrolyte ion concentrations of K ⁺ , Ca ²⁺ , Mg ²⁺ , Cl ⁻ , and CH ₃ COO ⁻ were measured using an ion chromatograph manufactured by Dionex. The results are shown in Table 2 below.

[0050]

[Table 2]

From the above results, it can be seen that the present preparation is a very homogeneous composition.

Comparative Example 1 The same electrolyte raw materials as in Table 1 except that acetic acid was excluded were ground to about 50 μm, and the mixed raw materials were granulated by a dry granulator and sized. Acetic acid was added to the obtained granules and mixed to obtain a preparation for dialysis. The average particle size of the obtained formulation is about 800 μm
Met.

Comparative Example 2 The same electrolyte raw materials as in Table 1 except that acetic acid was removed were ground to about 50 μm, and 5% by weight of water was added to the mixed raw materials and mixed. This mixture was granulated by an extrusion granulator and sized, and then dried at a temperature of 70 ° C. by a box dryer for 3 hours. Acetic acid was added to the obtained granules and mixed to obtain a preparation for dialysis. The average particle size of the obtained preparation was about 700 μm.

Comparative Example 3 The same electrolyte raw materials as in Table 1 except for acetic acid were dissolved in warm water (40 ° C.) with stirring in a stirring tank to obtain a concentrated aqueous solution having a concentration of about 25%. This concentrated aqueous solution is spray-dried in a continuous spray dryer (inlet temperature: 360 to 380 ° C., outlet temperature: 160 to 180 ° C.) from a nozzle having an orifice hole diameter of 1.3 m / m under a liquid sending pump pressure of 10 kg / cm ^2. Was. Acetic acid was added to the obtained granules and mixed to obtain a preparation for dialysis. The average particle size of the obtained preparation was about 200 μm.

FIG. 9 shows the X-ray diffraction results of Comparative Example 1, FIG. 10 shows Comparative Example 2 and FIG. 11 shows the X-ray diffraction results of Comparative Example 3 (X-ray: Cu K
α ₁ ).

As is clear from the comparison between FIG. 6 (Example 1) and FIGS. 9 to 11, only the X-ray diffraction chart of Example 1 shows that the water content of sodium acetate and calcium chloride was around 2θ = 7.0 °. The peaks of the double salt containing the other electrolyte composition and the pH adjuster formed by the thermal reaction are detected, and it can be seen that the peaks are clearly different from other X-ray diffraction results.

Next, the characteristics of the preparation will be described in detail below.

[0058]

[Table 3]

The dissolution rate was measured by placing 500 ml of water (20 ° C.) in a 1000 ml beaker and stirring with a stirrer (stirring speed 300 rpm) in Example 1 and Comparative Example 1.
150 g of each of the preparations Nos. To 3 was charged, and the time required for complete dissolution was measured.

As shown in Table 3, the preparation of the present invention has a higher bulk density and a higher particle density than the others, and also has a low angle of repose of 25 ° and good fluidity. You can see that.

Therefore, since the volume occupying the preparation is small,
It is possible to reduce transportation costs and storage space in hospitals and the like.

In addition, it is a preparation that is very easy to handle in preparing a dialysate, including its high dissolution rate and good flowability, and can be said to be an important preparation for powdering dialysis agents in the future.

Example 2 The raw materials shown in Table 4 below were used.

[0064]

[Table 4] Sodium chloride 250.20 kg Potassium chloride 6.15 kg Calcium chloride 9.07 kg Magnesium chloride 4.27 kg Sodium acetate 20.34 kg Acetic acid 4.96 kg Glucose 41.33 kg First, sodium chloride having an average particle size of about 350 μm is used, and potassium chloride, magnesium chloride, Sodium acetate, glucose and 4.7 liters of pure water were put into a double can type stirring mixer (steam heating) and heated while stirring to bring the content temperature to 60 ° C. Calcium chloride was added to the mixture and mixed.

After 15 minutes from the addition of calcium chloride, the content becomes slightly whiter, and when the content is further heated and mixed while maintaining the content temperature at 60 ° C., specific stickiness is produced in the content,
The particles of the contents began to adhere to each other. Then, when acetic acid was added and mixed, the specific stickiness slightly disappeared. afterwards,
The granulated product was taken out, sized, and dried to recover the product.

The average particle size of the obtained preparation is about 600 μm.

The X-ray diffraction (X-ray: Cu
As shown in Kα ₁ ), 2θ = 7.
It has a specific peak near 0 °, and the formation of a double salt generated by the hydrothermal reaction between sodium acetate and calcium chloride can be confirmed.

Example 3 The raw materials shown in Table 4 above were used.

First, using sodium chloride having an average particle size of about 350 μm, potassium chloride, magnesium chloride, sodium acetate and 4.7 liters of pure water are put into a double-can stirring mixer (steam heating), and the mixture is stirred. Heat to bring the contents temperature to 70 ° C. Calcium chloride was added to the mixture and mixed.

Fifteen minutes after the addition of calcium chloride, the content becomes slightly whiter, and if the content is further heated and mixed while maintaining the content temperature at 70 ° C., specific stickiness is produced in the content,
The particles of the contents began to adhere to each other. Then, the contents were taken out, sized, and dried.

The granules were placed in a stirring mixer, water was added to the granules at 1% and mixed, and the contents were heated to 50 ° C. When glucose was added thereto and mixed, specific stickiness was generated after 10 minutes, and after further mixing for 5 minutes, acetic acid was added and mixed. After 10 minutes, this specific stickiness disappears,
It turned into a fluffy granulate. The granulated product was dried until the water content became 0.5% or less, and the product was recovered.

The average particle size of the obtained preparation is about 600 μm
And the water content was 0.35%.

An electron microscope image of the preparation obtained in Example 3 is shown in FIG.
3 is shown.

A core layer (inner layer) composed of sodium chloride particles, a double salt layer (intermediate layer) containing acetic acid and another electrolyte composition formed by a hydrothermal reaction between sodium acetate and calcium chloride, and a glucose layer (outer layer) ) Clearly has a three-layer structure.

Next, the X-ray diffraction of Example 3 (X-ray: CuK
α ₁ ) is shown in FIG. In addition to the X-ray diffraction peak due to the raw materials used, a peak was detected near 2θ = 7.0 °, indicating that this was a double salt formed by the hydrothermal reaction of sodium acetate and calcium chloride.

Also, five samples were randomly taken from the obtained product, and for each sample, sample 8.161 was obtained.
g ⁺ 2.52 g of sodium bicarbonate as a second agent in water to make exactly 1000 ml, Na ⁺ ,
The electrolyte ion concentration of each of K ⁺ , Ca ²⁺ , Mg ²⁺ , Cl ⁻ , and CH ₃ COO ⁻ was measured by an ion chromatograph manufactured by Dionex, and the glucose concentration was measured by a liquid chromatograph.
The results are shown in Table 5 below.

[0077]

[Table 5]

From the above results, it can be seen that the present preparation is a very homogeneous composition.

Comparative Example 4 All the raw materials shown in Table 4 were put into a stirring mixer, mixed for 20 minutes, and then subjected to X-ray diffraction (X-ray: Cu
The results of Kα ₁ ) are shown in FIG. 15, but no peak was observed near 2θ = 7.0 ° as in Example 3.

On the other hand, the preparations of Example 3 and Comparative Example 4 were respectively filled in silica-deposited film bags and sealed by heat sealing.

A stability test was conducted at 40 ° C. (RH = 75%), and 20.4 g of a sample was dissolved by adding water to make exactly 100 ml. The absorbance was measured by a method for measuring 5-hydroxymethylfurfural in the solution. Table 6 shows the results.

[0082]

[Table 6]

From the results shown in Table 6, it can be seen that the preparation of the present invention has little glucose decomposed product even after 6 months.

[Brief description of the drawings]

FIG. 1 is a schematic view showing the structure of the preparation of the first invention.

FIG. 2 is a schematic view showing the structure of the preparation of the first invention.

FIG. 3 is a schematic view showing the structure of the preparation of the first invention.

FIG. 4 shows an optical microscope image of the solid dialysis agent obtained in Example 1.

FIG. 5 shows an electron microscopic image of the solid dialysis agent obtained in Example 1.

FIG. 6 shows the result of X-ray diffraction of the solid dialysis agent obtained in Example 1.

7 shows the results of electron microanalysis of the solid dialysis agent obtained in Example 1. FIG.

FIG. 8 shows the results of electron microanalysis of the solid dialysis agent obtained in Example 1.

9 shows the result of X-ray diffraction of the solid dialysis agent obtained in Comparative Example 1. FIG.

10 shows the result of X-ray diffraction of the solid dialysis agent obtained in Comparative Example 2. FIG.

FIG. 11 shows the result of X-ray diffraction of the solid dialysis agent obtained in Comparative Example 3.

FIG. 12 shows the results of X-ray diffraction of the solid dialysis agent obtained in Example 2.

FIG. 13 shows an electron microscopic image of the solid dialysis agent obtained in Example 3.

FIG. 14 shows the results of X-ray diffraction of the solid dialysis agent obtained in Example 3.

FIG. 15 shows the result of X-ray diffraction of the solid dialysis agent obtained in Comparative Example 4.

[Explanation of symbols]

 1 core layer 2 double salt layer 3 outer layer

──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. ⁶ Identification code FI A61K 33:06 31:19) (A61K 33/14 33:06 31:19 31:70) (56) References JP-A-6-178802 (JP, A) JP-A-6-279991 (JP, A) JP-A-8-169836 (JP, A) JP-A-7-59846 (JP, A) JP-A-4-257522 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 31/00-33/44

Claims (15)

(57) [Claims] 1. A solid dialysis agent comprising an electrolyte composition comprising sodium chloride, potassium chloride, calcium chloride, magnesium chloride and sodium acetate and a pH adjuster, at least one selected from the group consisting of sodium chloride and potassium chloride. A solid dialysis agent having a two-layer structure of a core layer containing as a main component, a double salt formed by the reaction of sodium acetate and calcium chloride, and a double salt layer containing another electrolyte composition and a pH adjuster. 2. The solid dialysis agent according to claim 1, wherein the double salt layer further contains glucose. 3. The core layer has an average particle size of 150 to 2,000.
3. The solid dialysis agent according to claim 1, which has a particle size of μm. 4. The method according to claim 1, wherein the pH adjuster is acetic acid.
3. The solid dialysis agent according to any one of 3. 5. A double salt formed by a reaction between sodium acetate and calcium chloride is obtained by X-ray diffraction at 2θ = 6 .
8 ° to 7.0 ° (X-ray: Cu λ (Kα1) = 1.54
The solid dialysis agent according to any one of claims 1 to 4, which has a specific peak at 0.05 angstrom). 6. A bicarbonate dialysis agent comprising the solid dialysis agent according to claim 1 and sodium bicarbonate. 7. A solid dialysis agent containing sodium chloride, potassium chloride, calcium chloride, magnesium chloride and sodium acetate, a pH adjuster and glucose, and at least one selected from the group consisting of sodium chloride and potassium chloride. A three-layer structure consisting of a core layer containing one type as a main component, a double salt formed by the reaction of sodium acetate and calcium chloride, a double salt layer containing another electrolyte composition and a pH adjuster, and an outer layer containing glucose. Solid dialysis agent. 8. The core layer has an average particle size of 150 to 2,000.
The solid dialysis agent according to claim 7, which has a particle size of µm. 9. The solid dialysis agent according to claim 7, wherein the pH adjuster is acetic acid. 10. A double salt formed by a reaction between sodium acetate and calcium chloride is determined by X-ray diffraction as 2θ =
6 . 8 ° to 7.0 ° (X-ray: Cu λ (Kα1) = 1.
The solid dialysis agent according to any one of claims 7 to 9, which has a specific peak at 5405 angstroms). 11. A bicarbonate dialysis agent comprising the solid dialysis agent according to claim 7 and sodium bicarbonate. 12. Water is added to a mixture of sodium chloride, potassium chloride, magnesium chloride and sodium acetate,
Calcium chloride is added under heating at an internal temperature of 50-100 ° C ,
And a mixing granulation step in which the content of water in the mixture when calcium chloride is added is 20 to 300 % by weight of the weight of calcium chloride , a granulating step, drying, and a step of adding and mixing a pH adjuster. A core layer containing at least one member selected from the group consisting of sodium chloride and potassium chloride as a main component, a double salt produced by a reaction between sodium acetate and calcium chloride, another electrolyte composition and pH adjustment A method for producing a solid dialysis agent having a two-layer structure with a double salt layer containing the agent. 13. A method of adding water to a mixture of sodium chloride, potassium chloride, magnesium chloride, sodium acetate and glucose, adding calcium chloride at an internal temperature of 50 to 80 ° C. , and adding calcium chloride. A mixing granulation step in which the content of water in the mixture is 20 to 100 % by weight of the weight of calcium chloride, and p after addition of calcium chloride
A core layer containing at least one member selected from the group consisting of sodium chloride and potassium chloride as a main component, comprising a step of adding and mixing an H adjuster, a step of sizing and drying; and a step of mixing sodium acetate and calcium chloride. Double salt, other electrolyte composition, glucose and pH produced by the reaction of
A method for producing a solid dialysis agent having a two-layer structure with a double salt layer containing a regulator. 14. Sodium chloride, potassium chloride, chloride
Adding water to the mixture of magnesium and sodium acetate,
Calcium chloride is added under heating at an internal temperature of 50-100 ° C,
And the water content of the mixture when calcium chloride is added.
The amount is 20-300% by weight of the weight of calcium chloride
Two layers obtained by mixing granulation process, sizing and drying processes
Glucose is added to the solid dialysis agent having the above structure while heating at an internal temperature of 30 to 80 ° C., and the mixture is mixed in the presence of 0.5 to 5.0% by weight of water of the total weight of the solid dialysis agent and glucose. A step of mixing and granulating the mixture, a step of adding and mixing a pH adjuster to the granulated substance, and a drying step, wherein at least one selected from the group consisting of sodium chloride and potassium chloride is used as a main component. Nuclear layer containing, double salt generated by the reaction of sodium acetate and calcium chloride, a double salt layer containing another electrolyte composition and a pH adjuster, and a solid dialysis agent having a three-layer structure of an outer layer containing glucose Production method. 15. The solid dialysis agent according to claim 1, comprising silicon oxide and having a water vapor transmission rate (40 ° C. 90
% RH) A packaged solid dialysis agent packaged in a packaging material of 2.0 g / cm ² · 24 hr or less.