JP2016209485A - Granulated substance for dialysis a agent and preparation method thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a technique for providing a granulated substance for an A agent with excellent storage stability, high hardness, and excellent solubility in the granulated substance for the A agent including no sodium chloride, but including sodium acetate, magnesium chloride, calcium chloride, and potassium chloride.SOLUTION: The granulated substance for the A agent includes no sodium chloride, but includes sodium acetate, magnesium chloride, calcium chloride, and potassium chloride. The granulated substance is so designed that a ratio of an integrated pore volume of pores with a pore diameter of 2,000-200,000 nm with respect to an integrated pore volume of pores with a pore diameter of 3-200,000 nm is 50% or less. This configuration can provide the granulated substance with excellent storage stability, high hardness, and excellent solubility.SELECTED DRAWING: None

Description

  The present invention relates to a granulated product used for dialysis agent A (hereinafter, granulated product for agent A) and a method for producing the same. More specifically, the present invention is a granulated product for agent A which does not contain sodium chloride but contains sodium acetate, magnesium chloride, calcium chloride and potassium chloride, and has excellent storage stability and high It is related with the granule for A agent provided with the outstanding solubility with hardness, and its manufacturing method. The present invention also relates to a dialysis agent A using the granule for the agent A and a dialysis agent using the agent A for dialysis.

  Currently, as a dialysis agent, a bicarbonate dialysis agent is mainly used, and a two-part type comprising a combination of many electrolyte components including sodium chloride and A agent containing glucose and B agent containing sodium bicarbonate. Are commercially available as common dialysis agents.

  Conventionally, the A agent for dialysis has the liquid A agent containing the electrolyte component in the form of a concentrated liquid and the solid A agent containing the electrolyte component in a solid state, but the liquid A agent is a transportation cost, storage space in a hospital, etc. In recent years, it has been regarded as a problem in terms of workability in hospitals, disposal of containers after use, etc. In recent years, solid-type dialysis agents A have become mainstream in Japan. In addition, in the solid A agent, in order to prevent uneven distribution of electrolyte components, particularly trace electrolyte components (for example, calcium chloride, magnesium chloride, sodium acetate, etc.), all or part of the electrolyte components are mixed or manufactured. Used in a grained state. On the other hand, since the dialysis agent B is a single composition, it is used in a powder state.

  Usually, the dialysis agent A contains sodium chloride, potassium chloride, calcium chloride, magnesium chloride, a pH regulator and glucose, and the dialysis agent B contains sodium bicarbonate. In recent years, a three-agent dialysis agent comprising an agent A containing an electrolyte component other than sodium chloride, an agent S containing sodium chloride, and an agent B containing sodium bicarbonate has also been proposed (see Patent Document 1). This three-part dialysis agent adjusts the ratio of the amount of S agent and B agent added during dialysis, allowing sodium and potassium to freely change the bicarbonate ion concentration during dialysis, depending on the patient's condition. It is possible to prepare a dialysate that can maintain a constant electrolyte concentration of calcium, magnesium, and the like.

  In general dialysis machines, dialysis agents, and dialysis techniques in Japan and overseas, the bicarbonate concentration in the dialysate is different from patient to patient, the patient's condition when starting dialysis, and during dialysis. However, there is a drawback that it cannot be set individually or changed over time according to the patient's condition or disease state, etc. If used, these drawbacks can be eliminated.

  However, Patent Document 1 mentions the points of storage stability, solubility, hardness, etc. of the solid dialysis agent A that does not contain sodium chloride but contains sodium acetate, magnesium chloride, calcium chloride, and potassium chloride. There is no room for further study.

  Sodium chloride is a hard crystalline particle that is chemically inert and stable compared to other trace electrolyte components (eg calcium chloride, magnesium chloride, sodium acetate, etc.) and has no water of crystallization. It is known that fluidity is good. In the solid dialysis agent A containing sodium chloride, even if the electrolyte component is granulated, sodium chloride is contained in the solid dialysis agent A because it contains 70% by weight or more of sodium chloride. It can suppress the interaction between other trace electrolytes, and can have excellent fluidity and high hardness.

  On the other hand, a granulated product not containing sodium chloride cannot receive various advantages obtained by subjecting such sodium chloride to granulation. Even if it is going to manufacture A agent, there exists a problem that other trace electrolytes interact at the time of manufacture, the viscosity of a raw material becomes large, cannot be provided with sufficient fluidity, and hardness also becomes low. Furthermore, the granulated product not containing sodium chloride also has drawbacks such as aggregation of fine particles when water is added to prepare the dialysate, resulting in poor solubility. The poor solubility in this case refers to the undissolved residue that is generated when the dialysis agent is dissolved to prepare the dialysis solution, and the dialysis agent having a low dissolution rate increases the risk of poor solubility.

  If undissolved dialysis agent is generated during dialysate preparation, the concentration of each electrolyte in the dialysate to be prepared does not become a preset concentration, resulting in a concentration abnormality. When dialysis is performed using a dialysate in which this concentration abnormality occurs, the electrolyte in the body is not corrected within the normal range, and in some cases, a serious electrolyte concentration abnormality may be caused. In order to prevent this, a dialysis agent dissolving apparatus and dialysis apparatus are provided with a safety device, but it is not desirable to operate the safety device in the first place. Therefore, in order not to cause poor solubility, it is important to use a preparation with good solubility (good dissolution rate) and use it within the required dissolution time set in the existing dissolution apparatus. It is necessary to ensure that the entire amount of dialysis agent is dissolved. As a dissolution apparatus widely used in dialysis facilities, for example, there is a fully automatic dissolution apparatus DAD-50NX-ST (manufactured by Nikkiso Co., Ltd.), and the dissolution time is set to about 4 minutes. In addition, the A agent dissolution apparatus AHI-502 (manufactured by Toa DKK Co., Ltd.) is also widely used as a dissolution apparatus. In this dissolution apparatus, a dialysis agent is added little by little to a predetermined amount of water stored in the apparatus. In addition, a system is adopted in which the addition is automatically stopped when the dialysate reaches a predetermined conductivity, and the time required for dissolution is set to about 9 minutes. When a dialysis agent with poor solubility (slow dissolution rate) is used in this dissolution apparatus, the dialysis solution that remains undissolved after the dialysate reaches the prescribed conductivity and the addition of the dialysis agent is stopped Concentration abnormalities occur because of a delayed dissolution. Thus, in the dissolution apparatus generally used in clinical practice, when the solubility of the dialysis agent used is poor, there is a concern that the quality of the resulting dialysate and the preparation efficiency may be greatly affected. Is done.

  On the other hand, Patent Document 2 discloses a granulated product for agent A containing potassium chloride, calcium chloride, magnesium chloride, and sodium acetate, with some or all of sodium chloride removed, to a saturated water vapor amount or less. A method of wet granulation using a humidified humidified gas is disclosed. In the wet granulation method described in Patent Document 2, the interaction between the electrolyte components occurs, but by controlling the humidity of the humidified gas, the increase in viscosity can be suppressed and the solid A agent for dialysis can be produced with high yield. However, Patent Document 2 does not touch on points such as storage stability, solubility, and hardness, and there remains room for further study.

  Moreover, in the solid A agent for dialysis marketed, in order to suppress the dispersion | variation in each electrolyte content for every individual package, the method of granulating the electrolyte containing sodium chloride and producing is common. Since sodium chloride is a highly crystalline substance, it has a high hardness, and a granulated product containing a large amount of sodium chloride necessarily has a high hardness. Therefore, it can be presumed that the hardness of the solid dialysis agent A containing no sodium chloride is lowered.

  If the hardness of the dialysis agent is low, it will be difficult to handle during production, distribution (transport) and preparation of dialysate, resulting in particle breakage and difficulty in handling. Become. However, it is difficult to obtain a granulated product for agent A having high hardness without using hard and inert sodium chloride. Furthermore, in general, when the hardness is increased, the solubility is lowered. Therefore, it is difficult to achieve both high hardness and excellent solubility in a granulated product that does not contain sodium chloride with the conventional technology. It has been.

Japanese Patent No. 5099464 JP2012-105964A

  The object of the present invention is a granulated product used for dialysis agent A, which does not contain sodium chloride, and is superior in a granulated product for agent A containing sodium acetate, magnesium chloride, calcium chloride, and potassium chloride. And a technology for providing excellent solubility with high storage stability and high hardness.

  The present inventor has conducted extensive studies to solve the above-mentioned problems. As a result, the granulated product used in the dialysis agent A does not contain sodium chloride, and includes sodium acetate, magnesium chloride, calcium chloride, and chloride. In the granulated product for agent A containing potassium, the ratio of the cumulative pore volume in the pore diameter of 2000 to 200,000 nm to the cumulative pore volume in the pore diameter of 3 to 200000 nm is designed to be 50% or less. The present inventors have found that excellent storage stability can be provided, and excellent solubility can be provided while having high hardness. Furthermore, the present inventor has prepared a mixture of sodium acetate and magnesium chloride in advance, and added calcium chloride and potassium chloride to the mixture to mix the electrolyte for the granule for agent A having the above characteristics. It has been found that a raw material is prepared and obtained by granulating the electrolyte raw material. The present invention has been completed by further studies based on these findings.

That is, this invention provides the invention of the aspect hung up below.
Item 1. A granulated product used for dialysis agent A,
Contains no sodium chloride, contains sodium acetate, magnesium chloride, calcium chloride, and potassium chloride,
The granulated product for agent A, wherein the ratio of the cumulative pore volume in the pore diameter of 2000 to 200,000 nm to the cumulative pore volume in the pore diameter of 3 to 200,000 nm is 50% or less.
Item 2. Item 2. The granule for agent A according to item 1, further comprising an organic acid.
Item 3. Item 3. The granule for agent A according to item 1 or 2, wherein the moisture content is 3.0% by weight or less.
Item 4. Item 4. The granule for agent A according to any one of items 1 to 3, wherein the hardness is 50 gf or more.
Item 5. Item A dialysis agent comprising the granule for agent A according to any one of items 1 to 4.
Item 6. Item 6. The dialysis agent A according to Item 5, further comprising glucose.
Item 7. Item 7. The dialysis agent A according to Item 5 or 6, further comprising sodium chloride.
Item 8. Item 8. A dialysis agent comprising the dialysis agent A according to any one of Items 5 to 7 and a dialysis agent B containing sodium bicarbonate.
Item 9. The dialysis agent A does not contain sodium chloride,
In addition, it contains S-dialysis agent containing sodium chloride,
Item 9. The dialysis agent according to Item 8, which is a three-part dialysis agent comprising the dialysis agent A, the dialysis agent B, and the dialysis agent S.
Item 10. The dialysis agent A contains sodium chloride,
Item 9. The dialysis agent according to Item 8, which is a two-agent dialysis agent comprising the dialysis agent A and the dialysis agent B.
Item 11. A method for producing a granulated product used for dialysis agent A, which does not contain sodium chloride and contains sodium acetate, magnesium chloride, calcium chloride, and potassium chloride,
A first step of mixing sodium acetate and magnesium chloride to obtain a first mixture;
A second step in which calcium chloride and potassium chloride are added to and mixed with the first mixture to obtain an electrolyte raw material;
A manufacturing method comprising: a third step of granulating the electrolyte material; and a fourth step of drying the granulated product obtained in the third step.
Item 12. Item 12. The manufacturing method according to Item 11, wherein the second step is performed by mixing calcium chloride and potassium chloride to obtain a second mixture, and then mixing the first mixture and the second mixture.
Item 13. Furthermore, the manufacturing method of claim | item 11 or 12 including the 5th process of adding an organic acid with respect to the granulated material obtained at the said 4th process.

  The granulated product for agent A of the present invention is granulated because the ratio of the cumulative pore volume in the pore diameter of 2000 to 200,000 nm to the cumulative pore volume in the pore diameter of 3 to 200000 nm is 50% or less. Less intrusion of water into the voids in the formed particles, the viscosity inside the granulated particles increases, the dispersibility deteriorates, and it is difficult to cause problems such as aggregation of particles and adhesion to containers Therefore, it has excellent solubility. Therefore, when preparing a dialysate using a commonly used dissolution apparatus, the dissolution can be prevented quickly, and at the same time the risk of abnormal dialysate concentration can be reduced. It is possible to prepare a stable dialysate stably and efficiently. Furthermore, the granulated product for agent A of the present invention is suppressed in solidification during storage and is excellent in terms of storage stability.

  Furthermore, since the granulated product for agent A of the present invention has a ratio of the cumulative pore volume of 50% or less, there are few voids in the granulated particles, that is, it is densely granulated. Because it has high hardness and can prevent particles from collapsing, eroding and pulverizing during manufacturing and transportation, it is possible to prevent environmental deterioration due to dust diffusion in manufacturing facilities and dialysis facilities. Become.

  Furthermore, according to the method for producing a granulated product for the agent A of the present invention, since no viscosity is generated during mixing of raw materials, there is no adhesion to a lump or a mixing device wall surface, and efficient production is possible. It becomes possible. Even in the step of mixing an organic acid such as acetic acid, excessive heat generation and generation of dust can be suppressed, so that the content uniformity of each component can be maintained. Moreover, according to the manufacturing method of the granule for A agent of this invention, since sodium chloride which occupies 70 weight% or more of the weight of a dialysis agent is not included in processes, such as mixing, granulation, and drying, it is manufactured. It is also possible to increase the efficiency significantly.

1. Granule for agent A The granule for agent A of the present invention is a granule used for the agent A for dialysis, which does not contain sodium chloride, sodium acetate, magnesium chloride, calcium chloride, and potassium chloride. The ratio of the cumulative pore volume in the pore diameter of 2000 to 200,000 nm to the cumulative pore volume in the pore diameter of 3 to 200,000 nm is 50% or less. Hereinafter, the granule for agent A of the present invention will be described in detail.

<Contained components>
In the granule for agent A of the present invention, sodium acetate is a substance that is a source of sodium ions and acetate ions.

  In addition, regarding the content of sodium acetate in the granulated product for agent A of the present invention, agent A so that the sodium ion concentration of the prepared dialysate is 120 to 150 mEq / L, preferably 135 to 145 mEq / L. The amount of sodium chloride used in combination with the granulated product for use, the content of other sodium salts contained in the granulated product for agent A, the content of the sodium salt contained in agent B, etc. For example, 40 to 70 parts by weight, preferably 45 to 65 parts by weight, and more preferably 50 to 65 parts by weight of sodium acetate per 100 parts by weight of the total amount of the granule for agent A of the present invention. In the present invention, the “total amount of the granule for agent A” refers to the total weight including crystal water and free water contained as necessary.

  In the granulated product for agent A of the present invention, magnesium chloride is a substance that becomes a supply source of magnesium ions and chloride ions. Magnesium chloride used as a raw material for producing the granulated product for agent A of the present invention may be either a hydrate or an anhydride, but part or all of the magnesium chloride is in the form of a hydrate. Preferably there is. When magnesium chloride hydrate is used, at least a part of the crystal water contained in the magnesium chloride hydrate is released by heating or heat generation during granulation, and serves as a binder, thereby efficiently using the electrolyte raw material. It becomes possible to granulate.

  Specific examples of magnesium chloride hydrate include magnesium chloride dihydrate, magnesium chloride tetrahydrate, magnesium chloride hexahydrate, magnesium chloride octahydrate, magnesium chloride dodecahydrate, etc. 1 to 12 hydrates. Among these magnesium chloride hydrates, magnesium chloride hexahydrate is preferable. These magnesium chloride hydrates may be used alone or in combination of two or more.

  Moreover, when using a part or all of magnesium chloride in the form of a hydrate as a manufacturing raw material of the granule for A agent of this invention, it is used as a manufacturing raw material of the granule for A agent of this invention. The ratio of magnesium chloride hydrate occupying the total amount of magnesium chloride is not particularly limited. For example, per 100 parts by weight of the total amount of magnesium chloride used as a raw material for producing the granule for agent A, for example, hexahydrate The proportion of the physical form of magnesium chloride is 40 to 100 parts by weight, preferably 70 to 100 parts by weight, and more preferably 100 parts by weight. Here, the total amount of magnesium chloride is the total weight calculated including the weight of water of crystallization (water molecules in the hydrate) when the magnesium chloride is in the form of a hydrate.

  In addition, regarding the content of magnesium chloride in the granulated product for agent A of the present invention, the magnesium ion concentration of the dialysate prepared by agent A for dialysis is 0.5 to 2.0 mEq / L, preferably 0.75. It may be set as appropriate in consideration of the content of other magnesium salts contained in the granulated product for agent A as necessary so as to be -1.5 mEq / L. For example, agent A of the present invention 1 to 50 parts by weight, preferably 1 to 25 parts by weight, and more preferably 1 to 15 parts by weight in terms of anhydrous magnesium chloride per 100 parts by weight of the granulated product. In the present invention, "anhydrous weight conversion of magnesium chloride" means that when magnesium chloride is in the form of hydrate, the weight of anhydride is excluded except for the weight of crystal water (water molecules in the hydrate). It is a value obtained by converting to.

  In the granule for agent A of the present invention, calcium chloride is a substance that is a source of calcium ions. Calcium chloride used as a raw material for producing the granule for agent A of the present invention may be either a hydrate or an anhydride, but a part or all of calcium chloride is in the form of a hydrate. Preferably there is. When calcium chloride hydrate is used, depending on the heating or exothermic conditions during granulation, at least a portion of the crystal water contained in the calcium chloride hydrate may be released and serve as a binder.

  Specific examples of calcium chloride hydrates include 1 to 6 hydrates such as calcium chloride monohydrate, calcium chloride dihydrate, calcium chloride tetrahydrate, and calcium chloride hexahydrate. Can be mentioned. Among these calcium chloride hydrates, calcium chloride dihydrate is preferable. These calcium chloride hydrates may be used singly or in combination of two or more.

  In addition, when a part or all of calcium chloride is used in the form of hydrate as a raw material for producing the granulated product for agent A of the present invention, it is used as a raw material for producing the granulated product for agent A of the present invention. The ratio of the calcium chloride hydrate to the total amount of calcium chloride is not particularly limited. For example, per 100 parts by weight of the total amount of calcium chloride used as a raw material for producing the granulated product for agent A, for example, two The proportion of calcium chloride in the hydrate form is 40 to 100 parts by weight, preferably 70 to 100 parts by weight, and more preferably 100 parts by weight. Here, the “total amount of calcium chloride” is the total weight calculated including the weight of crystal water (water molecules in the hydrate) when the calcium chloride is in the form of hydrate.

  In addition, regarding the calcium chloride content in the granulated product for agent A of the present invention, the calcium ion concentration of the dialysate prepared by agent A for dialysis is 1.5 to 4.5 mEq / L, preferably 2.5. It may be set as appropriate in consideration of the content of other calcium salts contained in the granulated product for agent A as necessary so as to be -3.5 mEq / L. For example, agent A of the present invention 1 to 75 parts by weight, preferably 5 to 50 parts by weight, and more preferably 10 to 35 parts by weight in terms of the anhydrous weight of calcium chloride per 100 parts by weight of the granulated product. In the present invention, “calcium chloride anhydrous weight conversion” means that when calcium chloride is in the form of hydrate, the weight of anhydride is excluded except for the weight of crystal water (water molecules in the hydrate). It is a value obtained by converting to.

  In the granulated product for agent A of the present invention, potassium chloride is a substance that is a source of potassium ions.

  Moreover, about content of the potassium chloride in the granulated material for A agent of this invention, it is for A agent so that the potassium ion concentration of the dialysate prepared with the A agent for dialysis may be 0.5-3 mEq / L. It may be set as appropriate considering the content of other potassium salts contained in the granulated product, for example, 3 to 25 wt.% Of potassium chloride per 100 parts by weight of the total amount of the granulated product for agent A of the present invention. Parts, preferably 10 to 20 parts by weight, more preferably 12 to 18 parts by weight.

  Furthermore, in addition to the above-mentioned components, the granulated product for the agent A of the present invention includes calcium ions, magnesium ions, sodium ions, potassium ions, chloride ions, acetate ions, citrate ions, and lactate ions as necessary. In addition, other organic acid salts and / or inorganic salts serving as a supply source of gluconate ions, succinate ions, malate ions, and the like may be included.

  Examples of the compound serving as a source of calcium ions include calcium salts of organic acids such as calcium acetate, calcium lactate, calcium citrate, calcium gluconate, calcium succinate, and calcium malate. These calcium salts of organic acids may be used alone or in combination of two or more.

  Examples of the compound serving as a supply source of magnesium ions include magnesium organic acid salts such as magnesium acetate, magnesium lactate, magnesium citrate, magnesium gluconate, magnesium succinate, and magnesium malate. One of these organic acid salts of magnesium may be used alone, or two or more thereof may be used in combination.

  Examples of the compound serving as the supply source of sodium ions include sodium organic acid salts such as sodium lactate, sodium citrate, sodium gluconate, sodium succinate, and sodium malate. These organic acid salts of sodium may be used alone or in combination of two or more.

  Examples of the compound serving as a source of potassium ions include potassium chloride, potassium acetate, potassium lactate, potassium citrate, potassium gluconate, potassium succinate, potassium malate, and other inorganic salts and / or organic acid salts of potassium. Can be mentioned. These inorganic salts and / or organic acid salts of potassium may be used singly or in combination of two or more.

  Examples of the compound serving as a supply source of acetate ions include alkali metal salts of acetic acid such as potassium acetate; alkali metal diacetates such as sodium diacetate and potassium diacetate. One of these alkali metal salts of acetic acid and alkali metal diacetate may be used alone, or two or more thereof may be used in combination.

  These organic acid salts and / or inorganic acid salts may be appropriately selected according to the types of various ions to be contained in the finally prepared dialysate.

  In the granulated product for agent A of the present invention, the content of these organic acid salt and / or inorganic salt is appropriately set according to the concentration of each ion provided in the finally prepared dialysate. Specifically, the content of the electrolyte component contained in the agent A takes into consideration the amount of the electrolyte component contained other than the granule for agent A, and the dialysate finally prepared is shown in Table 1 below. What is necessary is just to set suitably so that ion concentration may be satisfy | filled.

  Further, the granulated product for agent A of the present invention may contain an organic acid in order to adjust the pH of the finally prepared dialysate. In the conventional granule for agent A, when an organic acid is added as a pH adjuster, it tends to solidify during storage and easily deteriorate the fluidity. However, in the granule for agent A of the present invention, an organic acid is added. Even if it adds, solidification can fully be suppressed and the outstanding storage stability can be provided.

  The type of organic acid contained in the granulated product for agent A of the present invention is not particularly limited as long as it can be used for a dialysis agent. For example, acetic acid, citric acid, lactic acid, malic acid, fumaric acid, succinic acid , Malonic acid, gluconic acid and the like. Among these organic acids, acetic acid and citric acid are preferable, and acetic acid (particularly glacial acetic acid) is more preferable. These organic acids may be used alone or in combination of two or more.

  The content of the organic acid in the granulated product for agent A of the present invention is appropriately set according to the pH, the type of organic acid, etc. provided in the finally prepared dialysate. Specifically, the content of the organic acid in the granulated product for agent A of the present invention is such that the pH of the dialysate finally prepared is 7.2 to 7.6, preferably 7.2 to 7.5. What is necessary is just to set suitably so that it may become.

  The water content in the granulated product for agent A of the present invention is usually 3.0% by weight or less, preferably 2.5% by weight or less, more preferably 2.0% by weight or less. By setting it as such a low moisture content, the solidification at the time of storage can be suppressed more effectively, and the storage stability including the stability of glucose can be further improved. The water content in the present invention is a value measured using a Karl Fischer moisture meter.

<Physical properties>
The granulated product for the agent A of the present invention is expressed as a ratio of the cumulative pore volume at a pore diameter of 2000 to 200,000 nm to the cumulative pore volume at a pore diameter of 3 to 200,000 nm (hereinafter referred to as “particle pore volume ratio”). May satisfy 50% or less. Usually, the pore diameter of less than 2000 nm in the granule for agent A corresponds to the pores existing on the particle surface, and the pore diameter of 2000 nm or more is highly granulated such as secondary, tertiary, quaternary and more. This corresponds to the void volume within or between the particles. Particles with a large void volume in the granulated particles are fragile due to their low hardness, and the particle size distribution during transportation is likely to change, resulting in the generation of dust and storage stability in the medical field. Leads to worsening. In addition, the granulated product for agent A that does not contain sodium chloride has a property that the adhesion and viscosity of the particle surface is increased by a small amount of water because of its strong affinity with water, and it is difficult to dissolve. . In addition, when particles having a large void volume in the granulated particles are dissolved in water, water easily enters the voids in the granulated particles. For this reason, it is considered that in such particles with large inter-particle voids, the viscosity inside the particles increases as water enters the inside, and a slurry-like state is exhibited, thereby blocking new water intrusion. Once viscous particles have poor dispersibility, they tend to agglomerate particles and adhere to containers and dissolution devices, resulting in longer dissolution times or undissolved conditions, which is undesirable. . This phenomenon tends to become more prominent when a melting apparatus having a weak stirring force is used.

  In the present invention, since the void volume in the granulated particles and between the particles is small, the particle surface can be smoothly dissolved in water, and these problems can be solved. That is, in the present invention, the ratio of the void volume in and between the particles (that is, the particle gap volume ratio) satisfies the above range, thereby providing excellent storage stability and high hardness. However, it can be provided with excellent solubility.

  The particle gap volume in the granulated product for the agent A of the present invention may be 50% or less, but from the viewpoint of further improving the solidification suppressing action, hardness, and solubility, preferably 25 to 50%, More preferably, 30 to 50% is mentioned.

Further, in the granulated product for agent A of the present invention, the cumulative pore volume at a pore diameter of 3 to 200000 nm and the cumulative pore volume at a pore diameter of 2000 to 200000 nm satisfy the above-mentioned particle gap volume ratio. Specifically, as an integrated pore volume at a pore diameter of ^{3 to} 200000 nm, specifically, 0.1 to 0.5 cm ³ / g, preferably 0.1 to 0.4 cm ³ / g, more preferably include 0.15~0.35cm ³ / g, as the cumulative pore volume in the pore diameter 2000~200000nm, 0.03~0.3cm ³ / g, preferably 0.05 to 0. 25 cm ³ / g, more preferably include 0.02~0.05cm ³ / g.

  In the present invention, the cumulative pore volume at a pore diameter of 3 to 200,000 nm and the cumulative pore volume at a pore diameter of 2000 to 200,000 nm are determined by determining the contact angle of mercury in a mercury intrusion method using a mercury porosimeter. It is a value measured by setting the surface tension of mercury to 480 dyn / cm at 140 °.

  Further, the particle size of the granule for agent A of the present invention is not particularly limited. For example, it passes through a 10 mesh (aperture 1700 μm) sieve with a Tyler standard sieve, but is 80 mesh (aperture 180 μm). The proportion of particles that do not pass through the sieve is 90% by weight or more, preferably 93% by weight or more, and more preferably 95% by weight or more.

  The hardness of the granulated product for agent A of the present invention is usually 50 gf or more, preferably 50 to 200 gf, more preferably 50 to 150 gf. Since the granule for agent A of the present invention can have such a high hardness, it suppresses particle breakage during transportation or dialysate preparation, and suppresses changes in particle size distribution and generation of dust. Can do. In the present invention, “the hardness of the granule for agent A” is a granule for agent A at a measuring speed of 5 μm / sec using a hardness measuring instrument used for measuring the hardness of granules and having a flat-type measuring terminal at the tip. It is obtained by compressing the product and measuring the load when the granule for agent A is broken, and measuring the hardness of at least 10 granules for agent A, and calculating the average value thereof. is there.

In addition, the granule for agent A of the present invention has excellent solubility while having high hardness as described above. As the solubility of the granulated product for agent A of the present invention, for example, an agglomerated material for agent A having a solubility of 400 seconds or less, preferably 350 seconds or less under the following conditions is provided.
(Dissolution conditions)
In a state where a stirrer having a radius of 15 mm was rotated at 750 rpm in a 1 L beaker (bottom area 50 cm ² ), 44.13 g of the granulated product was added, and then purified water at 20 ° C. was added at a flow rate of 667 g / min. It is added along the wall from the top of the beaker for 2 seconds, and the dissolution time from the end of the addition of purified water to the complete dissolution of the granulated product is visually measured.

<Manufacturing method>
Although it does not restrict | limit especially about the manufacturing method of the granulated material for A agent of this invention, as long as it can provide the composition and physical property mentioned above, As a suitable example, the manufacturing method containing the following 1st process-4th process is mentioned. .
A first step of mixing sodium acetate and magnesium chloride to obtain a first mixture;
A second step in which calcium chloride and potassium chloride are added to and mixed with the first mixture to obtain an electrolyte raw material;
A third step of granulating the electrolyte raw material; and a fourth step of drying the granulated product obtained in the third step.
Hereinafter, the first to fourth steps will be described.

  In the first step, sodium acetate and magnesium chloride are mixed to prepare a first mixture. In the first mixture in which sodium acetate and magnesium chloride are mixed in advance, due to the interaction between the raw materials, a part of the crystal water contained in the magnesium chloride is released and the state moves to sodium acetate. By using the 1st mixture of such a state and implementing the said 2nd process-4th process, it becomes possible to obtain the granulated material for A agent provided with the physical property mentioned above.

  The first mixture obtained in the first step depends on the mixer to be selected so that the water of crystallization contained in magnesium chloride facilitates the interaction with sodium acetate, but for example, 5 minutes or more, preferably After mixing for 10 to 40 minutes so that the product temperature is 15 to 80 ° C., preferably 25 to 60 ° C., it is desirable to use for the second step described later.

  In the second step, calcium chloride and potassium chloride are added to and mixed with the first mixture to obtain an electrolyte raw material.

  In the second step, calcium chloride and potassium chloride may be added simultaneously or sequentially to the first mixture. However, after preparing a second mixture by mixing calcium chloride and potassium chloride in advance, It is desirable to mix two mixtures into the first mixture.

  When the granulated product for agent A of the present invention contains other organic acid salts and / or inorganic salts other than sodium acetate, magnesium chloride, calcium chloride and potassium chloride, these organic acid salts and / or Alternatively, the inorganic salt may be mixed with the first mixture together with calcium chloride and potassium chloride in the second step. In addition, in the preparation of the electrolyte raw material in the second step, if the second mixture is prepared in advance, these organic acid salts and / or inorganic salts may be contained in the second mixture.

  In addition, in the first step and / or the second step, free water may be added as necessary when preparing the first mixture, preparing the second mixture, and / or preparing the electrolyte raw material. Also good. When at least part of magnesium chloride or calcium chloride is in the form of hydrate, the crystal water derived from magnesium chloride or calcium chloride is released by heating or heat generation during granulation and functions as a binder. Although it may not be included, in such a case, in order to supplement the water functioning as a binder in addition to the crystal water that is released by heating or heat generation during granulation, free water is added. It may be left. In the present invention, “free water” refers to water that is added in a state in which it is not associated with other molecules, apart from crystallization water contained in a hydrate form in the electrolyte raw material.

  The amount of free water added in the first step and / or the second step may be appropriately set according to the content of magnesium chloride in the form of a hydrate, etc. 0-150 weight part with respect to a weight part, Preferably it is 0-100 weight part, More preferably, 0-50 weight part is mentioned. By adjusting the content of free water in the electrolyte raw material to the above range, it is possible to suppress the increase in the viscosity of the electrolyte raw material during granulation and more efficiently produce the granulated product for agent A, and it has high hardness. In addition, the solubility can be further improved, and further, solidification suppression during storage can be further improved, so that the storage stability can be significantly improved.

  In the third step, the electrolyte raw material obtained in the second step is granulated. In this way, by preparing a first mixture of sodium acetate and magnesium chloride in advance and granulating it using an electrolyte raw material obtained by mixing this with the remaining components, A having the above-mentioned particle gap volume ratio is obtained. It becomes possible to produce a granulated product for an agent.

  Granulation of the electrolyte raw material in the third step may be performed by a known granulation technique, and specific examples include granulation by stirring, heating or wet. By subjecting the electrolyte raw material to the granulation treatment, sodium acetate, magnesium chloride, calcium chloride and potassium chloride, and other organic acid salt and / or inorganic acid salt added as necessary, are combined, and A An agent granule is formed. In addition, since the electrolyte raw material interacts with sodium acetate and magnesium chloride in the first step, the increase in the viscosity of the electrolyte raw material during granulation is suppressed, and the granule for agent A is efficiently produced. It becomes possible to manufacture.

  The heating temperature at the time of granulation in the third step is not particularly limited, but is desirably 80 ° C. or lower. Further, the lower limit value of the heating temperature at the time of granulation is not particularly limited, but is preferably 30 ° C. or higher. If the temperature during granulation is below 30 ° C, the production efficiency may tend to decrease. If the temperature exceeds 80 ° C, excessive interaction occurs and a granulated product having an appropriate particle size is obtained. A tendency to become difficult may appear. From the viewpoint of further increasing storage stability, solubility, and hardness, the heating temperature during granulation is preferably 35 to 70 ° C.

  The heating method at the time of granulation is not particularly limited, and for example, a method of stirring as necessary while heating the mixer used for the preparation of the electrolyte raw material; Method: A method in which a fluidized bed of an electrolyte raw material is formed using a fluidized bed dryer (including a rolling fluidized bed dryer, a vibrating fluidized bed dryer, etc.) and heated.

  In the fourth step, the granulated product obtained in the third step is dried. What is necessary is just to set suitably the drying conditions in a 4th process in consideration of the supply rate of the granulated material used for a drying process in continuous manufacture, the moisture content of the granulated material for A agent manufactured, etc. For example, as a drying temperature, 100-180 degreeC, Preferably it is 130-170 degreeC, More preferably, 140-160 degreeC is mentioned. Moreover, as drying time, 1-45 minutes, Preferably it is 5-30 minutes, More preferably, 5-20 minutes is mentioned. In order to control the moisture content of the granulated dried product, it is desirable to monitor the exhaust temperature from the dryer.

  Moreover, what is necessary is just to implement the 5th process of adding an organic acid with respect to the granulated material after drying obtained at the said 4th process, when making the granulated material for A agent of this invention contain. When adding an organic acid to the granulated product after drying, if the temperature of the granulated product is high, the organic acid to be added will volatilize or decompose, so a cooling step is provided and the temperature of the granulated product is about 20-60 ° C. It is preferable to lower it down to. As the said temperature, More preferably, 20-40 degreeC, More preferably, 20-30 degreeC is mentioned.

2. A agent for dialysis The A agent for dialysis of the present invention contains the granulated product for the A agent. The dialysis agent A of the present invention may be composed only of the granulated product for the agent A, and may contain other compounds used in the dialysis agent as necessary. .

  For example, the dialysis agent A of the present invention may contain glucose together with the granule for agent A for the purpose of maintaining the blood glucose level of the patient. Glucose tends to be destabilized by contact with electrolytes such as calcium chloride and magnesium chloride. However, in the dialysis agent A of the present invention, glucose is contained by using the granule for the agent A. However, glucose can be maintained stably.

  The content of glucose in the dialysis agent A of the present invention is appropriately set according to the glucose concentration provided in the finally prepared dialysate. Specifically, the content of glucose in the dialysis agent A of the present invention is such that the glucose concentration in the finally prepared dialysate is 0 to 2.5 g / L, preferably 1.0 to 1.5 g / L. What is necessary is just to set suitably so that it may become L.

  Further, the dialysis agent A of the present invention may contain sodium chloride, if necessary. When sodium chloride is contained in the dialysis agent A, the dialysis agent A of the present invention is used as a two-part dialysis agent together with the B agent containing sodium bicarbonate.

  Regarding the content of sodium chloride in the dialysis agent A of the present invention, the dialysis solution to be finally prepared satisfies each ion concentration shown in Table 1 in consideration of the amount of sodium salt in the dialysis agent A and the like. What is necessary is just to set suitably.

  Moreover, when the organic acid is not contained in the granule for A agent, or when the pH of the dialysate finally prepared is insufficient with the organic acid contained in the granule for A agent In addition, the A agent for dialysis of the present invention may contain an organic acid separately from the granulated product for the A agent. About the kind of organic acid to contain, it is the same as that which can be mix | blended with the granule for A agent, However As an organic acid to contain separately from the said A agent granule, it is solid at normal temperature. The organic acid is preferred. What is necessary is just to set suitably about the quantity of the organic acid to contain in this way, as long as the pH with which the dialysate prepared finally is equipped can satisfy the range mentioned above.

  The dialysis agent A of the present invention is used as a dialysis agent for preparing a bicarbonate dialysis solution together with a dialysis agent B containing sodium bicarbonate.

3. Dialysis Agent The dialysis agent of the present invention contains the dialysis agent A and the dialysis agent B containing sodium bicarbonate.

  The dialysis agent B may contain glucose as necessary. When glucose is contained in the dialysis agent B, the content thereof is such that the glucose concentration in the dialysate to be finally prepared is 0 to 2.5 g / L, preferably 1.0 to 1.5 g / L. What is necessary is just to set suitably. However, it is desirable that the dialysis agent B does not contain an electrolyte component other than sodium bicarbonate, and it is preferable that the component is substantially composed of sodium bicarbonate. The dialysis agent B is preferably solid from the viewpoint of transportation and storage. Specific examples of the shape of the solid dialysis agent B include powders and granules.

  What is necessary is just to set the usage-amount of the said B agent for dialysis suitably so that the bicarbonate ion in the dialysate finally prepared may be 20-40 mEq / L, Preferably it is 25-35 mEq / L.

  When sodium chloride is contained in the dialysis agent A, the dialysis agent of the present invention is a two-part dialysis agent comprising the dialysis agent A and a dialysis agent B containing sodium bicarbonate. Used as.

  When sodium chloride is not contained in the dialysis agent A, the dialysis agent of the present invention is the dialysis agent A, dialysis agent S containing sodium chloride, and dialysis agent containing sodium bicarbonate. It is used as a three-part dialysis agent consisting of B agent. As described in Patent Document 1, the three-part dialysis agent is adjusted according to the patient's condition by adjusting the ratio of the addition amount of the dialysis agent S and the dialysis agent B during dialysis. It is possible to prepare a dialysate that can maintain a constant electrolyte concentration such as sodium, potassium, calcium, magnesium, etc. while freely changing the bicarbonate ion concentration even during dialysis.

  The dialysis agent S may contain glucose as necessary. When glucose is contained in the dialysis agent S, the content thereof is such that the glucose concentration in the dialysate finally prepared is 0 to 2.5 g / L, preferably 1.0 to 1.5 g / L. What is necessary is just to set suitably. However, it is desirable that the dialysis agent S does not contain any electrolyte component other than sodium chloride, and it is preferable that the contained component substantially consists of sodium chloride. The dialysis agent S is preferably solid from the viewpoint of transportation and storage. Specific examples of the shape of the solid S-dialysis agent include powders and granules.

  The use amount of the dialysis S agent is appropriately set so that the dialysate finally prepared satisfies the sodium concentration shown in Table 1 in consideration of the amount of sodium salt in the dialysis agent A and the like. Good.

  The dialysis agent of the present invention is used to prepare a bicarbonate dialysate. Specifically, when sodium chloride is not contained in the dialysis agent A, the dialysis agent B, and the dialysis agent A, the dialysis agent S is added to a predetermined amount of water (preferably purified water). The bicarbonate dialysate is prepared by mixing and diluting.

  Hereinafter, the present invention will be specifically described with reference to examples. However, the present invention is not construed as being limited to the following examples.

Example 1
First mixed 77.4 kg of magnesium chloride hexahydrate and 500 kg of sodium acetate with a Nauta mixer (manufacturer: Hosokawa Micron Corporation, model number: DBX-5000RW) for about 30 minutes until the product temperature is about 50 ° C. Got. Separately, 113.7 kg of potassium chloride and 168.1 kg of calcium chloride dihydrate were mixed for about 30 minutes with a Nauta mixer (manufacturer: Hosokawa Micron Corporation, model number: DBX-5000RW) to obtain a second mixture. Next, the first mixture and the second mixture are continuously supplied to a Laedige mixer (manufacturer: Chuo Kiko Co., Ltd., model number: KM150D (W)) so that the weight ratio is about 2: 1, and the spindle rotation speed is 180 rpm. Operation was performed to obtain a granulated product. The resulting granulated product was sized and dried with a gyro dryer GD-120 type at a drying temperature of about 5 minutes at a drying temperature of 155 ° C. to obtain a granulated product for agent A.

Example 2
A first mixture was obtained by mixing 31.0 kg of magnesium chloride hexahydrate and 200 kg of sodium acetate. Moreover, 45.5 kg of potassium chloride and 67.2 kg of calcium chloride dihydrate were mixed to obtain a second mixture. The subsequent steps were performed in the same manner as in Example 1 to obtain a granulated product for agent A.

Example 3
First mixture of 4.02 kg of magnesium chloride hexahydrate and 25.98 kg of sodium acetate with Nauta mixer (manufacturer: Hosokawa Micron Corporation, model number: NX-2J) for about 15 minutes until the product temperature is about 40 ° C. Got. 5.38 kg of the obtained first mixture was put into a vertical granulator (manufacturer: POWREC Co., Ltd., model number: FM-VG25), stirring was started at a main shaft of 100 rpm and a chopper of 150 rpm, and the mixture was previously mixed in a plastic bag. A second mixture consisting of 1.06 kg of potassium chloride and 1.56 kg of calcium chloride dihydrate was added and granulated to obtain a granulated product. 3 kg of this granulated product was dried at 150 ° C. for 10 minutes with a fluidized bed dryer (manufacturer: Nagato Electric Works Co., Ltd., model number: 10F type) to obtain a granulated product for agent A.

Example 4
First mix by mixing 2.28 kg of magnesium chloride hexahydrate and 11.02 kg of sodium acetate for about 20 minutes with Nauta mixer (manufacturer: Hosokawa Micron Corporation, model number: NX-2J) until the product temperature is about 35 ° C. Got. 6.68 kg of the obtained first mixture was put into a vertical granulator (manufacturer: POWREC, model number: FM-VG25), and stirring was started at a main shaft of 100 rpm and a chopper of 150 rpm. 2.48 kg of hydrate was added in order and granulated to obtain a granulated product. 3 kg of the granulated product was dried at 130 ° C. for 12 minutes with a fluidized bed dryer (manufacturer: Nagato Electric Works Co., Ltd., model number: 10F type) to obtain a granulated product for agent A.

Comparative Example 1
6.27 kg of potassium chloride, 9.27 kg of calcium chloride dihydrate, 4.27 kg of magnesium chloride hexahydrate, and 27.56 kg of sodium acetate were mixed with a Nauta mixer (manufacturer: Hosokawa Micron Corporation, model number: NX-2J). The electrolyte raw material was obtained. 3 kg of this electrolyte raw material is heated at 90 ° C. for 18 minutes in a fluidized bed dryer (manufacturer: Nagato Electric Works Co., Ltd., model number: 10F type) and dried together with granulation to obtain a granulated product for agent A It was.

Comparative Example 2
It mixed similarly to the comparative example 1, and obtained the electrolyte raw material. 2 kg of this electrolyte raw material is placed on a metal vat, heated with a constant temperature dryer (manufacturer: Advantech Co., Ltd., model: DRS420DA) at 80 ° C. for 300 minutes, dried together with granulation, and granulated product for agent A Got.

Comparative Example 3
0.265 kg of potassium chloride, 0.391 kg of calcium chloride dihydrate, 0.180 kg of magnesium chloride hexahydrate, and 1.164 kg of sodium acetate were mixed to obtain an electrolyte raw material. This electrolyte raw material is put into a rolling fluidized bed granulation coating device (manufacturer: POWREC Co., Ltd., model number FD-MP-01S type), and a stirring blade and a rotor disk are rotated at 300 rpm, temperature 30 ° C., humidity 27% RH. The air was blown at a flow rate of 0.8 m ³ / min and mixed and stirred for 25 minutes for granulation. Under this spraying condition, the electrolyte material was granulated in a state where 194 parts by weight of free water was supplied per 100 parts by weight in terms of anhydrous magnesium chloride. After granulation, drying was performed for 15 minutes at a flow rate of 2.0 m ³ / min using dry air at 80 ° C. and a relative humidity of 0.76% RH to obtain a granulated product for agent A.

Comparative Example 4
Granulation for agent A under the same conditions as in Comparative Example 3 except that the drying conditions after granulation were changed to 110 minutes using dry air with a relative humidity of 0.76% RH and the drying time was changed to 18 minutes. I got a thing.

(2) Physical property evaluation of granule for A agent (2-1) Particle size distribution The particle size distribution of each obtained granule for A agent was calculated | required. Each granulated product for agent A is sieved with a Tyler standard sieve with a 10 mesh (mesh opening size 1700 μm) sieve, and then 10 g is obtained with a robot shifter (manufacturer: Seishin Co., Ltd., model number: RPS-105). 16 mesh (aperture 1700 μm), 24 mesh (aperture 710 μm), 32 mesh (aperture 500 μm), 42 mesh (aperture 355 μm), 60 mesh (aperture 250 μm), 80 mesh (aperture 180 μm), Using a sieve of 100 mesh (aperture 150 μm) and 150 mesh (aperture 106 μm), depending on the measurement conditions of sound intensity 20, sound frequency 51 Hz, classification time 5 minutes, sweep time 0.3 minutes, pulse interval 1 second The particle size distribution was measured by a sieving method.

  The obtained results are shown in Table 2. The granulated product for agent A in Examples 1 to 4 has a larger particle diameter because the granulation has advanced to a higher degree than in Comparative Examples 1 to 4, and thus the bonding between particles is further promoted. A granulated product was obtained, and the ratio of fine powder having a particle size of 180 μm or less (particles having passed through 80 mesh) was also considerably lower than those of Comparative Examples 3 and 4.

(2-2) Moisture content The moisture content of the granulated product for each agent A was measured using a Karl Fischer moisture meter (manufacturer: Hiranuma Sangyo Co., Ltd., model number AVQ-6).

  The obtained results are shown in Table 3. In the granule for agent A of Examples 1 to 4, the water content was 3.0% by weight or less, and the water was sufficiently removed.

(3) Manufacture of granulated product for agent A containing organic acid To 1 kg of granulated product for agent A obtained above, glacial acetic acid was added in the amount shown in Table 4 as a pH adjuster, mixed, and mixed. Granules for containing A agent were obtained (Examples 5 to 8 and Comparative Examples 5 to 8).

(4) Physical properties and performance evaluation of granulated product for agent A containing organic acid (4-1) Storage stability and solubility of granulated product for agent A containing acetic acid After being packaged in a polyethylene bag, it was stored for 1 day under an environment of 20 ° C. and 40% RH under a load of 30 kg. The granulated product for acetic acid-containing agent A after storage was passed through a sieve having an opening of 1.7 mm by natural dropping, and the weight ratio of the solidified material remaining on the sieve was calculated as the solidification rate.

In addition, the granule for agent A (Examples 5 to 8 and Comparative Example 8), which has a mesh size of 1.7 mm after storage and hardly solidified, is left as it is, and acetic acid-containing A in which the ratio of solidification is large after storage. About the granule for an agent (Comparative Examples 5-7), after grind | pulverizing lightly, the solubility to water was measured using what passed the sieve of 1.7 mm of mesh openings. Specifically, a stirrer having a radius of 15 mm was rotated at 750 rpm in a 1 L beaker having an empty bottom area of 50 cm ² , and 44.13 g of the granulated product for acetic acid-containing agent A was passed through the sieve. Purified water was added along the wall from the top of the beaker for 90 seconds at a flow rate of 667 g / min. The time from the completion of the addition of purified water to the complete dissolution of the granulated product for acetic acid-containing agent A was determined as the dissolution time.

  The results obtained are shown in Table 5. The granulated product for acetic acid-containing agent A of Examples 5 to 8 was less solidified after addition of acetic acid as a pH adjuster and excellent in solubility as compared with Comparative Examples 5 to 8. In addition, since the granulated product for acetic acid-containing agent A of Examples 5 to 8 has a small particle gap volume ratio and is more closely granulated particles, the particles were maintained without being broken even during mixing with acetic acid. As a result, solidification was suppressed, and further excellent solubility was obtained.

(4-2) Hardness The hardness of each granule for acetic acid-containing agent A obtained in Examples 5 and 6 and Comparative Examples 5 to 8 was measured. The hardness was measured with a hardness meter ("New Grano", manufactured by Okada Seiko Co., Ltd.) using a low load measuring terminal (flat type) at a measurement speed of 5 μm / sec. Each particle was measured and the average value was obtained.

  The results obtained are shown in Table 6. In the granulated product for acetic acid-containing agent A of Examples 5 and 6, the average hardness shows a high value exceeding 50 gf, and the particles can be sufficiently suppressed from collapsing and pulverizing during transportation and dialysate preparation. It was a thing.

(4-3) Cumulative pore volume distribution The cumulative pore volume distribution was measured for the granulated product for acetic acid-containing agent A. Specifically, using a mercury porosimeter (“poremaster 60GT”, manufactured by Quantachrome), 0.1 g of a sample is enclosed in a measurement cell, the mercury contact angle is set to 140 °, and the mercury surface tension is set to 480 dyn / cm. The integrated pore volume distribution was then measured. The pore volume was calculated using analysis software “Poremaster”. The analysis range was 3 to 200,000 nm. Further, from the cumulative pore volume distribution of the obtained granules for acetic acid-containing agent A, the particle gap volume ratio was calculated according to the following formula.
Particle pore volume ratio (%) = {(cumulative pore volume at a pore diameter of 2000 to 200000 nm) / (cumulative pore volume at a pore diameter of 3 to 200000 nm)} × 100

  The obtained results are shown in Tables 7-9. From this result, in the granulated product for acetic acid-containing agent A of Examples 5 to 8, the cumulative pore volume at a pore diameter of 2000 to 200000 nm is small as compared with Comparative Examples 5 to 8, that is, granulated particles. It was clarified that each of the contained raw material electrolytes was tightly packed with few internal voids. On the other hand, the cumulative pore volume at a pore diameter of 3 to 2000 nm was comparable in both the examples and the comparative examples. Further, in the granulated product for acetic acid-containing agent A of Examples 5 to 8, the particle gap volume ratio is 50% or less, whereas in Comparative Examples 5 to 8, the particle gap volume ratio exceeds 50%. It was.

  The cumulative pore volume at a pore diameter of 2000 to 200,000 nm includes the void volume inside the particles of secondary particles, tertiary particles, or particles formed as higher-order particles. The larger the void volume, the easier the water to enter the void, and a portion having a strong viscosity is formed inside the particle. As a result, aggregation and adhesion occur, resulting in poor solubility. In the granulated product for acetic acid-containing agent A of Examples 5 to 8, the void volume is small, and the particle gap volume ratio is 50% or less, so it is considered that excellent solubility was exhibited. In addition, it is considered that the granules for acetic acid-containing agent A of Examples 5 to 8 exhibited high hardness based on the small pore volume, that is, the dense granulation. From the above results, in the granulated product for acetic acid-containing agent A of Examples 5 to 8, the particle gap volume ratio is 50% or less, that is, formed as secondary particles, tertiary particles, or higher order particles. Since the void volume inside the particles in the formed particles is small, it has excellent storage stability and can be provided with excellent solubility while having high hardness. On the other hand, when the void volume is large, the portion is exposed to the air, so that not only the particle surface but also the particle surface forming the void is easily affected by the humidity of the environment. As a result, consolidation due to moisture absorption is likely to occur, and when glucose coexists, the granule for agent A having a large void volume is not preferable because it affects the stability.

Claims (13)

A granulated product used for dialysis agent A,
Contains no sodium chloride, contains sodium acetate, magnesium chloride, calcium chloride, and potassium chloride,
The granulated product for agent A, wherein the ratio of the cumulative pore volume in the pore diameter of 2000 to 200,000 nm to the cumulative pore volume in the pore diameter of 3 to 200,000 nm is 50% or less.   Furthermore, the granule for A agent of Claim 1 containing an organic acid.   The granule for agent A according to claim 1 or 2, wherein the water content is 3.0% by weight or less.   The granulated product for agent A according to any one of claims 1 to 3, having a hardness of 50 gf or more.   The A agent for dialysis containing the granule for A agent in any one of Claims 1-4.   The dialysis agent A according to claim 5, further comprising glucose.   The dialysis agent A according to claim 5 or 6, further comprising sodium chloride.   A dialysis agent comprising the dialysis agent A according to any one of claims 5 to 7 and a dialysis agent B containing sodium bicarbonate. The dialysis agent A does not contain sodium chloride,
In addition, it contains S-dialysis agent containing sodium chloride,
The dialysis agent according to claim 8, which is a three-part dialysis agent comprising the dialysis agent A, the dialysis agent B, and the dialysis agent S. The dialysis agent A contains sodium chloride,
The dialysis agent according to claim 8, which is a two-part dialysis agent comprising the dialysis agent A and the dialysis agent B. A method for producing a granulated product used for dialysis agent A, which does not contain sodium chloride and contains sodium acetate, magnesium chloride, calcium chloride, and potassium chloride,
A first step of mixing sodium acetate and magnesium chloride to obtain a first mixture;
A second step in which calcium chloride and potassium chloride are added to and mixed with the first mixture to obtain an electrolyte raw material;
A manufacturing method comprising: a third step of granulating the electrolyte material; and a fourth step of drying the granulated product obtained in the third step.   The manufacturing method according to claim 11, wherein the second step is performed by mixing calcium chloride and potassium chloride to obtain a second mixture, and then mixing the first mixture and the second mixture.   Furthermore, the manufacturing method of Claim 11 or 12 including the 5th process of adding an organic acid with respect to the granulated material obtained at the said 4th process.