TWI772408B - Agent A for hemodialysis - Google Patents

Abstract

As far as the subject matter of the present case is concerned, the object of the present invention is to provide a solid A agent for hemodialysis, which can reduce the odor of acetic acid, and can further suppress the solidification caused by storage and make When glucose coexists, the decomposition of glucose and the increase in pH when dissolved in water are excellent, and the storage stability is excellent. The solution of the present case is that the aforementioned problem can be solved by including a first component and a second component in a solid A agent for hemodialysis; wherein, the first component is substantially only composed of magnesium chloride and potassium chloride. One is composed of granules containing calcium chloride, and the second component contains acetic acid and acetate.

Description

Agent A for hemodialysis

Technical Field The present invention relates to an agent A for hemodialysis comprising acetic acid and an acetate salt, and a method for producing the agent A for hemodialysis. More specifically, the present invention relates to a solid hemodialysis agent A and a method for producing the same. The solid hemodialysis agent A contains acetic acid and acetate, and can reduce the odor of acetic acid, and can further reduce the odor of acetic acid. It suppresses solidification due to storage, decomposes glucose when coexisting with glucose, and increases pH when dissolved in water, and has excellent storage stability. Furthermore, the present invention relates to an agent for hemodialysis using the agent A for hemodialysis.

Background Art Dialysis therapy for patients with renal insufficiency is performed to adjust the concentration of electrolyte components in blood, remove uremic substances, correct acid-base balance, and the like. Generally, the dialysis therapy performed is roughly divided into peritoneal dialysis and hemodialysis, and dialysate is used in either method.

The dialysate contains a number of components, and should be blended in an appropriate concentration with the components that are stable in preparation, meet the purpose of treatment, and have less burden on the body. For example, the dialysate used in peritoneal dialysis usually mainly uses sodium lactate as an alkalizing agent, while the dialysate used in hemodialysis contains sodium bicarbonate, sodium acetate, sodium citrate, etc. The components suitable for each dialysis method are selected from the viewpoint of route and biocompatibility.

In addition, it is known that in general, compared with hemodialysis, the dialysis efficiency of peritoneal dialysis is slow, the burden on the heart and cells is small, and the reduction of renal function is also slow compared with hemodialysis. On the other hand, hemodialysis is usually performed about 3 times a week, and each dialysis is performed for about 4 to 5 hours. During the dialysis treatment, water and metabolic decomposition products in the body are removed at a relatively fast rate, so it often causes inconvenience. Disequilibrium syndrome or low blood pressure.

From this difference in dialysis efficiency, there are also differences in the formulation of the dialysate used in peritoneal dialysis and hemodialysis. For example, many hemodialysis agents currently on the market in the world contain potassium, and no potassium-free hemodialysis agents are sold in Japan. Hemodialysis has good time efficiency, and in the absence of potassium, there is a risk of hypokalemia due to the rapid removal of potassium ions, so it contains potassium chloride at a concentration not lower than the fatal danger zone. On the other hand, in patients with renal insufficiency, since potassium is an electrolyte that should be adequately removed, it is reasonable that a peritoneal dialysis agent for dialysis does not contain potassium. For example, Patent Document 1 discloses a peritoneal dialysis solution for patients with renal insufficiency requiring nutritional management and/or blood sugar management, which is characterized by containing glucose as an osmotic pressure regulating substance and containing sodium at each concentration within a predetermined range ions (Na ⁺ ), calcium ions (Ca ⁺ ), magnesium ions (Mg ⁺ ) are used as cations, and chloride ions (Cl ^- ) and/or organic acid ions are contained as anions, and the type and concentration of the organic acid are Change and adjust the water removal performance.

When the hemodialysis agent is in the liquid form, the transportation cost is high due to its bulky volume, and a storage space commensurate with it is also required. Therefore, the use of solid preparations has been mainstream in Japan in recent years. Since the solid preparation is prepared by dissolving a predetermined amount of water in a predetermined amount of water before dialysis treatment, it is not necessary to transport a large volume of dialysate, and the burden on medical practitioners can be reduced.

The solid hemodialysis agent was originally composed of three doses: A-1 dose containing electrolytes and pH adjusters, A-2 dose consisting only of glucose, and B dose consisting of sodium bicarbonate. Many dialysis agents circulating in Japan are two-dose solid hemodialysis agents consisting of agent A and agent B. Usually, agent A contains sodium chloride, potassium chloride, calcium chloride, magnesium chloride, a pH adjuster (as a buffer component of acid and optional components), and glucose, and agent B contains sodium bicarbonate. In addition, in order to prevent the precipitation of insoluble salts, it is taboo to mix calcium chloride and magnesium chloride with the B agent. In addition, for example, Patent Document 2 proposes a three-dose form of a hemodialysis agent, which is composed of a main component that can change the bicarbonate ion concentration and the sodium ion concentration according to the patient's condition during dialysis treatment. A component of electrolyte components (other than sodium bicarbonate and sodium chloride), S component mainly containing sodium chloride, and B component mainly containing sodium bicarbonate.

Today, the bicarbonate dialysis agent used as a hemodialysis agent is formulated to have the composition and concentration shown in Table 1 below when it is clinically used as a dialysate. [Table 1]

Agent A for hemodialysis usually contains acetic acid as a pH adjuster. Since acetic acid can be metabolized in a short time, there is little accumulation in the living body, and the pH when hemodialysis agent A is dissolved is higher than that when citric acid or hydrochloric acid is contained, so it has little effect on skin or machinery. Therefore, hemodialysis agents containing acetic acid are widely used not only in solid preparations but also in liquid preparations.

A general solid preparation in pharmaceuticals requires a special preparation technique different from that of a liquid preparation in that a desired component is uniformly and stably maintained in a desired amount in at least a part. If it is in a liquid state, since all the components are melted and are in a uniform state, there is no problem in the uniformity of the content of the components, but it is not easy to achieve a state where the content is uniformly contained in a solid preparation.

In the case of a solid hemodialysis agent, generally, a part or all of the electrolyte components contained in it are processed into a state of being mixed or granulated, and it goes without saying that the content uniformity is improved. Many other issues are also addressed. For example, Patent Document 3 discloses a dialysis agent capable of improving production efficiency while suppressing variation in the amount of components contained in a granular material (granulated material) and a method for producing the same. In addition, Patent Document 4 discloses that when the ratio of a specific cumulative pore volume is set to 50% or less by granulation, a granulated product for agent A excellent in solubility, curing inhibition during storage, and the like can be obtained.

In addition, in recent years, the lower the total acetate ion content in the dialysate, the more ideal it is physiologically, and the society has also reported that the ideal is less than 6mEq/L or less than 4mEq/L, and the development of a device that can be set at a low total acetate ion content is increasingly demanded. Hemodialysis agents.

When the solid hemodialysis agent A contains acetic acid as a pH adjuster, the acetic acid smell frequently becomes a problem. Plus, acetic acid can sometimes react with other ingredients and cause cure. In addition, acetic acid is also a major factor that promotes the decomposition of glucose, and glucose is generally contained widely in agent A for hemodialysis.

Conventionally, various proposals have been made regarding a method for reducing the acetic acid smell caused by volatilization of the acetic acid contained in the hemodialysis agent A. For example, Patent Document 5 discloses that the dialysis agent A used for preparing the bicarbonate dialysate contains acetic acid and acetate so that the molar ratio of acetic acid:acetate is 1:0.5 to 2, Furthermore, it becomes possible to prepare the bicarbonated dialysate so that the total acetate ion concentration is 2 mEq/L or more and less than 6 mEq/L, and the stability of the components in agent A for dialysis can be improved, and the acetic acid smell can be reduced. Furthermore, in Patent Document 6, the solid agent A for dialysis used for preparing a bicarbonate dialysate contains glucose, acetic acid and acetate, and at least a part of the acetic acid and acetate is an alkali metal diacetate, and is By setting the molar ratio of acetic acid:acetate to 1:0.5 to 2, it becomes possible to prepare a bicarbonate dialysate with a total acetate ion concentration of 2 mEq/L or more and less than 6 mEq/L. The stability of the ingredients is excellent, and the acetic acid smell can also be reduced. In this way, in order to realize the suppression of solidification during storage, the reduction of acetic acid odor, and the suppression of deterioration of glucose, etc., several attempts have been made in the prior art. However, the means for solving the problems of the prior art have only been limited to: using the method of using the difference in physical properties due to the production method, or the method of responsiveness such as setting restrictions on the contained components, for the granulated material and other components coexisting, for all components. It cannot be said that the understanding of the most suitable form or composition of the content is sufficient, and there is room for improvement in the method of reducing the acetic acid smell in particular.

Prior Art Document Patent Document Patent Document 1: Japanese Patent Laid-Open No. 2001-190662 Patent Document 2: Japanese Patent Laid-Open No. 5099464 Patent Document 3: Japanese Patent Laid-Open No. 2012-105964 Patent Document 4: Japanese Patent Laid-Open No. 2016-209485 Gazette Patent Document 5: Japanese Patent No. 5376480 Patent Document 6: Japanese Patent No. 5517321

SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION An object of the present invention is to provide a solid agent A for hemodialysis, which can reduce the acetic acid smell, further suppress solidification due to storage, decompose glucose when coexisting with glucose, and dissolve in The pH at the time of water rises, and the storage stability is excellent.

MEANS TO SOLVE THE PROBLEM The inventors of the present invention have found that, in the case of solid hemodialysis agent A, coexistence of the first component and the second component suppresses the acetic acid The volatilization of the acetic acid can reduce the smell of acetic acid; the first component is composed of granules containing only one of magnesium chloride and potassium chloride, and calcium chloride, and the second component contains acetic acid and acetate . Furthermore, it has been found that the solid state agent A for hemodialysis can suppress the solidification due to storage, suppress the increase in pH when dissolved in water, and suppress the decomposition and coloring of glucose even if it is coexisted with glucose, and has excellent properties. Storage stability. In particular, it was found that the solid state agent A for hemodialysis, even in the state where the first component and the second component have been evenly divided, can reduce acetic acid odor, inhibit curing due to storage, and inhibit dissolution. The pH rises in the presence of water, and even if it is coexisted with glucose, the decomposition and coloring of glucose are suppressed, and it has excellent storage stability. The present invention has been completed by further repeated investigations based on such knowledge.

That is, the present invention provides inventions described in the following aspects. Item 1. A solid agent A for hemodialysis comprising a first component and a second component, wherein the first component contains substantially only magnesium chloride and potassium chloride One is a granulated product containing calcium chloride, wherein the second component contains acetic acid and acetate. Item 2. The solid agent A for hemodialysis according to Item 1, wherein the first component contains magnesium chloride. Item 3. The solid agent A for hemodialysis according to Item 1 or 2, wherein the first component contains magnesium chloride, and the second component contains potassium chloride. Item 4. The solid agent A for hemodialysis according to Item 1, wherein the first component contains potassium chloride, and the second component contains magnesium chloride. Item 5. The solid agent A for hemodialysis according to any one of Items 1 to 4, which contains acetic acid and an alkali metal acetate salt as the acetic acid and the acetate salt. Item 6. The solid agent A for hemodialysis according to any one of Items 1 to 4, which comprises an alkali metal diacetate salt as the aforementioned acetic acid and an acetate salt. Item 7. The solid agent A for hemodialysis according to any one of Items 1 to 4, which comprises a homoacetate compound as the aforementioned acetic acid and acetate. Item 8. The solid agent A for hemodialysis according to any one of Items 1 to 7, wherein the first component and/or the second component contains sodium chloride. Item 9. The solid-state agent A for hemodialysis according to any one of Items 1 to 8, wherein the first component contains sodium chloride. Item 10. The solid agent A for hemodialysis according to any one of Items 1 to 9, wherein the first component and/or the second component contains glucose. Item 11. The solid-state agent A for hemodialysis according to any one of Items 1 to 10, wherein the second component contains glucose. Item 12. A 2-dose type hemodialysis agent comprising: the solid-state agent A for hemodialysis according to any one of Items 1 to 11, and the agent B for hemodialysis comprising sodium bicarbonate. Item 13. A 3-dose formulation for hemodialysis, comprising: the solid-state agent A for hemodialysis shown in any one of Items 1 to 7, 10, and 11 that does not contain sodium chloride, and blood containing sodium chloride Agent S for dialysis and agent B for hemodialysis containing sodium bicarbonate. Item 14. A method for producing a solid agent A for hemodialysis, comprising a first step and a second step: wherein the first step is to prepare substantially only one of magnesium chloride and potassium chloride, and also contain chloride A calcium granulate, the second step is to obtain a solid hemodialysis agent A, which contains the granulate obtained in the first step, acetic acid and acetate.

Effects of the Invention The agent A for hemodialysis of the present invention can effectively suppress the volatilization of acetic acid, thereby reducing the odor of acetic acid. Furthermore, the agent A for hemodialysis of the present invention is capable of suppressing solidification due to storage, decomposition of glucose when coexisting with glucose, and pH increase when dissolved in water, and has excellent storage stability. Therefore, according to the agent A for hemodialysis of the present invention, it becomes possible to improve the quality of the agent for hemodialysis, improve the use environment in the medical field, and the like.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Forms for Carrying Out the Invention 1. Agent A for Hemodialysis in Solid Form The agent A for hemodialysis of the present invention is characterized in that it is a solid hemodialysis agent comprising a first component and a second component Agent A is used; the first component is a granulated product containing substantially only one of magnesium chloride and potassium chloride, and calcium chloride; the second component includes acetic acid and acetate. In this way, in the agent A for hemodialysis, the first component formed of the granulated material of the specific component and the second component containing the specific component coexist by formulation, and it becomes possible to reduce acetic acid. Smell, inhibition of solidification due to storage, inhibition of decomposition of glucose when coexisting with glucose, and inhibition of pH rise when dissolved in water. Hereinafter, the agent A for hemodialysis of the present invention will be described in detail.

<The 1st component> The 1st component contained in the agent A for hemodialysis of this invention is a granulated material which contains only one of magnesium chloride and potassium chloride substantially, and also contains calcium chloride. The term "granulated product" in the present invention refers not only to a state in which each component particle is agglomerated or reacted, but a state in which multiple component particles are mixed in one particle, but also refers to a state of agglomerate in which one particle is combined with each other.

Magnesium chloride is a substance that becomes a supply source of magnesium ions and chloride ions. As the magnesium chloride used as a raw material for the production of the first component, either a hydrate or an anhydride can be used, but a part or all of the magnesium chloride is preferably in the form of a hydrate. When magnesium chloride hydrate is used, at least part of the crystal water contained in the magnesium chloride hydrate is desorbed by heating or exotherm during granulation to function as a binder, and the electrolyte raw material can be efficiently granulated. Specific examples of the hydrate of magnesium chloride include 1 to 12 hydrates such as magnesium chloride dihydrate, magnesium chloride tetrahydrate, magnesium chloride hexahydrate, magnesium chloride octahydrate, and magnesium chloride dodecahydrate. Among these magnesium chloride hydrates, magnesium chloride hexahydrate is preferably mentioned. These magnesium chloride hydrates may be used alone or in combination of two or more.

Potassium chloride is a substance that becomes a supply source of potassium ions.

In the first component, substantially only one of magnesium chloride and potassium chloride is contained. Here, "contain only one of them substantially" means that one of potassium chloride and magnesium chloride is contained, and the other is not substantially contained. That is, magnesium chloride and potassium chloride do not substantially coexist in the same component. Therefore, the first component can be divided into two aspects: the first aspect that contains magnesium chloride and does not substantially contain potassium chloride, and the second aspect that contains potassium chloride and does not substantially contain magnesium chloride.

In the case where the first component is the above-mentioned first aspect, the content of magnesium chloride in the first component is appropriately set in consideration of the content of other magnesium salts contained in the dialysis agent, so that the hemodialysis agent A The magnesium ion concentration of the prepared hemodialysate is 0.5 to 2.0 mEq/L, preferably 0.75 to 1.5 mEq/L. For example, for every 100 parts by weight of the total amount of the first component, magnesium chloride is used. In terms of the weight of the anhydride, it is 0.1 to 50 parts by weight, preferably 0.1 to 40 parts by weight, and more preferably 0.3 to 30 parts by weight. In the present invention, "magnesium chloride anhydride weight conversion" refers to a value obtained by converting the weight of crystal water (water molecules in the hydrate) to the weight of anhydride when magnesium chloride is in a hydrate form.

When the first component is the first aspect, the first component does not substantially contain potassium chloride. Here, the term "substantially does not contain potassium chloride" means that a small amount of potassium chloride is allowed to be contained within the range that does not impair the effect of the present invention. The total amount of potassium chloride is 1 part by weight or less, preferably less than 0.3 part by weight, more preferably 0 part by weight.

Also, when the first component is the second aspect, the content of potassium chloride in the second component is appropriately set in consideration of the content of other potassium salts contained in the dialysis agent, so that by The potassium ion concentration of the hemodialysis solution prepared with the hemodialysis agent A may be 0.5 to 3 mEq/L. For example, per 100 parts by weight of the total amount of the first component, potassium chloride is 0.1 to 50 The weight part is preferably 0.1 to 40 parts by weight, more preferably 0.3 to 30 parts by weight.

When the first component is the second aspect, the first component does not substantially contain magnesium chloride. Here, "substantially free of magnesium chloride" means that a small amount of magnesium chloride is allowed to be contained within a range that does not impair the effect of the present invention, and specifically, the total amount per 100 parts by weight of the first component Magnesium chloride is 1 part by weight or less in terms of anhydride weight, preferably less than 0.3 part by weight, and more preferably 0 part by weight.

Calcium chloride is a substance that becomes a supply source of calcium ions. As the calcium chloride used as a raw material for the production of the first component, either a hydrate or an anhydride may be used, but a part or all of the calcium chloride is preferably in a hydrated form. When a hydrate of calcium chloride is used, at least a part of the crystal water contained in the hydrate of calcium chloride may be released due to heating or exothermic conditions during granulation, and it may also function as a binder. Specific examples of the hydrate of calcium chloride include 1 to hexahydrate such as calcium chloride monohydrate, calcium chloride dihydrate, calcium chloride tetrahydrate, and calcium chloride hexahydrate. Among these calcium chloride hydrates, calcium chloride dihydrate is preferably used. These calcium chloride hydrates may be used alone or in combination of two or more.

The content of calcium chloride in the first component is appropriately set in consideration of the content of other calcium salts contained in the dialysis agent, so that the calcium ion concentration of the hemodialysate prepared with agent A for hemodialysis becomes 1.5 It may be 4.5 mEq/L, preferably 2.5 to 3.5 mEq/L. For example, the total amount of the first component per 100 parts by weight is 0.1 to 70 weight parts in terms of the weight of the anhydride of calcium chloride. parts, preferably 0.1 to 60 parts by weight, more preferably 0.3 to 50 parts by weight. In the present invention, the so-called "anhydride weight conversion of calcium chloride" is obtained by converting the weight of crystal water (water molecules in the hydrate) to the weight of anhydride when calcium chloride is in the form of hydrate. value.

The first component is a form in which the above-mentioned components are granulated together with other components blended as necessary to obtain a granulated product. The particle size of the granulated material constituting the first component is not particularly limited. For example, a Tyler standard sieve may pass through a 10-mesh (1700 μm mesh) sieve, but not through an 80-mesh (180 μm mesh) sieve. The ratio of the particles in the sieve is 90% by weight or more, preferably 93% by weight or more, and more preferably 95% by weight or more.

<Second component> The second component is a component containing acetic acid and acetate. In the agent A for hemodialysis of the present invention, all the components other than the granules constituting the first component are the components of the second component.

The acetic acid used in the second component may also be glacial acetic acid. In addition, the acetate used in the second component is not particularly limited as long as it is acceptable as the lipid component of the hemodialysis fluid. For example, alkali metal acetates such as sodium acetate and potassium acetate; calcium acetate, Magnesium acetate and other alkaline earth metal salts of acetate. These acetates can also be anhydrous acetates. Among these acetates, from the viewpoints of safety and cost based on actual results of use over many years, preferably, alkali metal acetates are used, and more preferably, sodium acetate is used. Moreover, these acetates may be used individually by 1 type, and may be used in combination of 2 or more types.

In addition, at least a part of the acetic acid and the acetate salt contained in the second component may be in the form of an alkali metal diacetate. By using the alkali metal diacetate, it becomes possible to further effectively plan the reduction of acetic acid odor, the suppression of solidification due to storage, the suppression of decomposition of glucose when coexisting with glucose, and the suppression of pH increase when dissolved in water. The so-called alkali metal diacetate is a complex (MH(C ₂ H ₃ O ₂ ) ₂ ; M represents an alkali metal atom) formed by compounding 1 mol of acetic acid alkali metal salt and 1 mol of acetic acid. Alkali metal diacetate, 1 molar acetate (alkali metal acetate) and 1 molar acetic acid are supplied. Specific examples of the alkali metal diacetate used in the present invention include sodium diacetate, potassium diacetate, and the like. These alkali metal diacetates may be used alone or in combination of two or more. Among the alkali metal diacetate salts, sodium diacetate is preferably used.

In addition, at least a part of the acetic acid and the acetate salt contained in the second component may be in the form of a higher acetate compound. The so-called higher acetate compound is a compound formed by combining acetic acid (primary compound) and acetate (primary compound). By using the alkali metal diacetate, it becomes possible to further effectively plan the reduction of acetic acid odor, the suppression of solidification due to storage, the suppression of decomposition of glucose when coexisting with glucose, and the suppression of pH increase when dissolved in water.

In the second component, the molar ratio of acetic acid and acetate salt is not particularly limited, and may be appropriately set based on the range of pH given to the hemodialysate. For example, as the second component, acetic acid: acetate The molar ratio can be exemplified: preferably 1:0.5 to 10, more preferably 1:0.5 to 3.0, particularly preferably 1:0.7 to 2.0. Here, when an alkali metal diacetate is included as acetic acid and acetate, acetic acid and acetate derived from 1 mol of alkali metal diacetate are calculated as 1 mol of acetic acid and 1 mol of acetate The aforementioned mol ratio. In addition, when a higher acetate compound is included as acetic acid and acetate, if the molar ratio of acetic acid: acetate in the higher acetate compound is 1:X, it is derived from 1 mole of the higher acetic acid The acetic acid and the acetate salt of the salt compound were calculated from the above-mentioned molar ratio using 1 molar acetic acid and X molar acetate.

The content of acetic acid and acetate in the second component is appropriately set so that the acetate ion concentration of the hemodialysis solution prepared with the hemodialysis agent A is 0.5 to 12 mEq/L, preferably 1.5 to 10 mEq/L. L is more preferably 2 to 6mEq/L, for example, the total amount of the second component per 100 parts by weight, the total amount of acetic acid and acetate is 1 to 100 parts by weight, preferably 5 to 80 parts by weight, more preferably 5 to 25 parts by weight.

Moreover, when the said 1st component is a 1st aspect (that is, the aspect which does not contain potassium chloride substantially), a 2nd component may contain potassium chloride. When the second component contains potassium chloride, its content is appropriately set in consideration of the content of other potassium salts contained in the hemodialysis agent, so that the potassium ion concentration of the hemodialysis solution becomes 0.5 to 3 mEq/ L is fine.

Moreover, when the said 1st component is a 2nd aspect (namely, the aspect which does not contain magnesium chloride substantially), the 2nd component may contain magnesium chloride. When magnesium chloride is contained in the second component, the content is appropriately set in consideration of the content of other magnesium salts contained in the hemodialysis agent A, so that the magnesium ion concentration of the hemodialysis solution becomes 0.5 to 2.0 mEq/ L may preferably be 0.75 to 1.5 mEq/L.

The second component may be in the form of a non-granulated product containing the aforementioned components and other components blended as required, or may be in the form of a granulated product together with the aforementioned components and other components blended as required . Further, the second component may be a combination of a non-granulated product and a granulated product.

In the container containing the agent A for hemodialysis of the present invention, the second component can exist in a state in which the above-mentioned components and other components blended according to needs are uniformly dispersed, and the above-mentioned components can also be mixed with Other components blended according to need exist in a state of unevenly dispersed or distributed.

<Sodium chloride> The agent A for hemodialysis of the present invention may contain sodium chloride as a supply source of sodium ions. When the agent A for hemodialysis of the present invention contains sodium chloride, the sodium chloride may be contained in either the first component or the second component, or may be contained in the first component and the second component Divide the two.

When the agent A for hemodialysis of the present invention contains sodium chloride, the content of sodium chloride is appropriately set in consideration of the content of other sodium salts contained in the agent for hemodialysis, so that the agent prepared by agent A for hemodialysis can be appropriately set. The sodium ion concentration of the blood dialysate may be 120 to 150 mEq/L, preferably 135 to 145 mEq/L.

<Glucose> The agent A for hemodialysis of the present invention may contain glucose for the purpose of maintaining the blood sugar level of the patient. Glucose tends to be destabilized by contact with electrolytes such as calcium chloride and magnesium chloride. In the hemodialysis agent A of the present invention, the first component is in the form of granules and the first component is in the form of granules. The coexistence of the two components enables stable maintenance of glucose even if it contains glucose.

When the agent A for hemodialysis of the present invention contains glucose, the glucose may be contained in either the first component or the second component, or may be contained in both the first component and the second component. However, from the viewpoint of further improving the stability of glucose, it is preferably contained in the second component.

When the agent A for hemodialysis of the present invention contains sodium chloride, the content is appropriately set according to the glucose concentration to be contained in the hemodialysate to be finally prepared. Specifically, the content of glucose in the hemodialysis agent A is appropriately set so that the final prepared dialysate has a glucose concentration of 0 to 2.5 g/L, preferably 1.0 to 2.0 g/L.

<Other components> The agent A for hemodialysis of the present invention may contain calcium ions, magnesium ions, sodium ions, potassium ions, chloride ions, citric acid ions, and lactic acid, in addition to the aforementioned components, as necessary. Other organic acid salts and/or inorganic salts of supply sources such as ions, gluconate ions, succinate ions, malate ions, etc. When these components are contained, they may be contained in either of the first component and the second component, or may be contained in both the first component and the second component.

As a compound which becomes a supply source of calcium ion, calcium salts of organic acids, such as calcium acetate, calcium lactate, calcium citrate, calcium gluconate, calcium succinate, and calcium malate, are mentioned, for example. These calcium salts of organic acids may be used alone or in combination of two or more.

As a compound which becomes a supply source of magnesium ion, the organic acid salt of magnesium, such as magnesium acetate, magnesium lactate, magnesium citrate, magnesium gluconate, magnesium succinate, magnesium malate, is mentioned, for example. These organic acid salts of magnesium may be used alone or in combination of two or more.

As a compound which becomes a supply source of sodium ion, the organic acid salt of sodium, such as sodium lactate, sodium citrate, sodium gluconate, sodium succinate, and sodium malate, is mentioned, for example. These organic acid salts of sodium may be used alone or in combination of two or more.

As a compound which becomes a supply source of potassium ion, the organic acid salt of potassium, such as potassium acetate, potassium lactate, potassium citrate, potassium gluconate, potassium succinate, and potassium malate, is mentioned, for example. These potassium organic acid salts may be used individually by 1 type, and may be used in combination of 2 or more types.

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 final prepared hemodialysis solution.

In the agent A for hemodialysis of the present invention, the content of these organic acid salts and/or inorganic salts is appropriately set according to the concentration of each ion to be contained in the final hemodialysis solution. Specifically, the content of the electrolyte component contained in the hemodialysis agent A of the present invention may be appropriately set so that the final hemodialysate prepared satisfies each ion concentration shown in Table 2 below.

[Table 2]

In the agent A for hemodialysis of the present invention, by containing acetic acid and acetate in the second component, the prepared hemodialysis solution can have an appropriate pH, but in the agent A for hemodialysis of the present invention For example, pH adjusters other than acetic acid and acetate may be further contained according to need. The pH adjusting agent that can be used in the hemodialysis agent A of the present invention is not particularly limited as long as it is acceptable as a component of the dialysate. For example, liquid acids such as hydrochloric acid, lactic acid, and gluconic acid, and lemon Acid, succinic acid, fumaric acid, malic acid, glucono-delta-lactone and other solid acids, and their sodium, potassium, calcium, magnesium salts, and the like. Among these pH adjusters, organic acids are suitably used. A pH adjuster may be used individually by 1 type, and may be used in combination of 2 or more types.

Furthermore, when the agent A for hemodialysis of the present invention contains a pH adjuster other than acetic acid and acetate, the pH adjuster may be contained in either the first component or the second component, or may be contained in either of the first component and the second component. Both the first component and the second component.

When the agent A for hemodialysis of the present invention contains a pH adjuster other than acetic acid and acetate, the content is appropriately set so that the pH of the finally prepared hemodialysis solution is 7.2 to 7.6, preferably 7.2 to 7.2 7.5 will do.

<Containing aspect of the first component and the second component> The agent A for hemodialysis of the present invention is contained in a state where the first component and the second component coexist. In the agent A for hemodialysis of the present invention, the first component and the second component may coexist in the container. For example, the first component and the second component may be uniformly dispersed. The first component and the second component may be unevenly dispersed or distributed. <Production method> The agent A for hemodialysis of the present invention is produced by preparing a granulated product constituting the first component, and mixing the components contained in the second component into the granulated product. Specifically, the method for producing the agent A for hemodialysis of the present invention includes a method including the following first and second steps. Step 1: Preparation of a granulated product containing substantially only one of magnesium chloride and potassium chloride and containing calcium chloride. Step 2: Obtaining a solid A agent for hemodialysis, the agent A for hemodialysis comprising: the granulated product obtained in the aforementioned first step, and acetic acid and acetate.

What is necessary is just to granulate using the component contained in the 1st component in the said 1st step. The granulation can be performed by a method generally employed in this technical field.

The granulated product obtained in the above-mentioned first step can also be subjected to post-processing such as drying, cooling, sieving, etc. as required. Especially in the case of drying, it is very dependent on the total amount of crystal water of the raw material used. As an indicator, it is preferable to dry the raw material used so that 80 parts by weight to 20 parts by weight of all the crystal water originally kept are removed per 100 parts by weight of the raw material. It is further preferable to remove 80 to 40 parts by weight, particularly preferably 75 to 50 parts by weight of crystal water. By sufficiently drying the granulated material within the temperature range where the raw material does not decompose, it becomes possible to further effectively plan: reducing acetic acid odor, inhibiting solidification, and improving its stability in the case of containing glucose.

In the second step, the granulated product (first component) obtained in the first step may be mixed or added with the components constituting the second component. In the above-mentioned second step, the components constituting the second component may be separately added to the granulated product (first component) obtained in the first step, or the components constituting the second component may be added together. After being mixed briefly, the mixture was added. As for the second component, in the case of containing acetic acid and acetate, in the aforementioned second step, after temporarily mixing acetic acid and acetate, adding or mixing to the composition obtained in the first step Granules, it becomes possible to further effectively plan: reduce acetic acid odor, inhibit solidification, and improve its stability when containing glucose.

2. Agent for hemodialysis The agent for hemodialysis of the present invention comprises the aforementioned agent A for hemodialysis and agent B for hemodialysis containing sodium bicarbonate.

Glucose may be contained in the said B agent for hemodialysis according to need. When the aforementioned agent B for hemodialysis contains glucose, its content is appropriately set so that the glucose concentration in the finally prepared hemodialysis solution is 0 to 2.5 g/L, preferably 1.0 to 1.5 g/L. Can. However, the aforementioned agent B for hemodialysis desirably does not contain electrolyte components other than sodium bicarbonate, and preferably contains components substantially composed of sodium bicarbonate. From the viewpoint of transportation and storage, the aforementioned agent B for hemodialysis is ideal in a tethered state. Moreover, as the shape of the solid B agent for hemodialysis, a powder agent, a granule agent, etc. are mentioned specifically,.

The usage amount of the aforementioned agent B for hemodialysis is appropriately set so that the bicarbonate ion in the final hemodialysis solution is 20 to 40 mEq/L, preferably 25 to 35 mEq/L.

When the aforementioned agent A for hemodialysis contains sodium chloride, the agent for hemodialysis of the present invention is composed of the aforementioned agent A for hemodialysis and agent B for hemodialysis containing sodium bicarbonate, and is a two-dosage form of hemodialysis. used with the agent.

In addition, in the case where the aforementioned agent A for hemodialysis does not contain sodium chloride, the agent for hemodialysis of the present invention is composed of the aforementioned agent A for hemodialysis, agent S for hemodialysis containing sodium chloride, and a hemodialysis agent containing sodium chloride. It is composed of the hemodialysis agent B of sodium carbonate, and it is used as a hemodialysis agent in 3 dosage forms. As described in Patent Document 2, the three-dose type hemodialysis agent can be prepared in accordance with the patient's condition by adjusting the ratio of the addition amount of hemodialysis agent S to hemodialysis agent B during hemodialysis. Even during hemodialysis, the concentration of bicarbonate ions can be freely changed, while the concentration of electrolytes such as sodium, potassium, calcium, and magnesium can be maintained in the hemodialysis solution at a constant level.

Glucose may be contained in the said S agent for hemodialysis as needed. When the aforementioned S agent for hemodialysis contains glucose, its content is appropriately set so that the glucose concentration in the finally prepared hemodialysis solution is 0 to 2.5 g/L, preferably 1.0 to 1.5 g/L. Can. However, the S agent for hemodialysis desirably does not contain electrolyte components other than sodium chloride, and a suitable system contains components that are substantially composed of sodium chloride. From the viewpoint of transportation and storage, the aforementioned S agent for hemodialysis is ideal in a tethered state. Moreover, as the shape of the solid S agent for hemodialysis, a powder agent, a granule agent, etc. are mentioned specifically,.

The amount of the hemodialysis agent S to be used is appropriately set according to the amount of sodium salt in the hemodialysis agent A, and the hemodialysate finally prepared satisfies the sodium concentration shown in Table 1 above.

The agent for hemodialysis of the present invention is used to prepare a bicarbonated hemodialysis solution. Specifically, the hemodialysis agent A, the hemodialysis agent B, and the hemodialysis agent S when the hemodialysis agent A does not contain sodium chloride are mixed to a predetermined amount. The water (preferably purified water) is diluted to prepare a bicarbonated hemodialysis solution. [Example]

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

Test Example 1 1. Preparation of solid hemodialysis agent A Example 1 928.8 g of sodium chloride, 28.2 g of calcium chloride dihydrate, and 18.0 g of magnesium chloride hexahydrate were measured, and put into separate plastic bags to In a closed state, the temperature was heated to 70°C with a blower type shelf dryer (shelf dryer). After heating, these raw materials and 18.0 g of purified water were placed in a plastic bag and sealed, and after being thoroughly mixed, they were placed in an air-supplied tray dryer again and allowed to stand at 70° C. for 20 minutes. Next, the entire contents of the plastic bag were filled in the stainless steel tank so as to be uniform, and the contents were placed in a blower rack dryer at 130° C., and dried for 2 hours. Since the granulated product is solidified by drying, it was pulverized with a spoon twice during drying, and after the drying was completed, it was passed through a sieve with a mesh opening of 2000 μm to produce a granulated product (first component).

Measure 118.70 g of the obtained granules (the first component), 5.27 g of a solid mixture of acetic acid and sodium acetate with a molar ratio of acetic acid:sodium acetate of 1:1 (the second component), 26.25 g of glucose ( The second component), after fully mixing in a plastic bag, put into a moisture-proof packaging material containing an aluminum laminate layer and sealed to obtain a solid hemodialysis agent A.

Example 2 Measure 928.8g of sodium chloride, 25.3g of potassium chloride, and 28.2g of calcium chloride dihydrate, respectively, put them into separate plastic bags to keep them in a sealed state, and use an air-supplied tray dryer to heat to 70 °C. After heating, these raw materials and 18.0 g of purified water were placed in a plastic bag and sealed, and after being thoroughly mixed, they were placed in an air-supplied tray dryer again and allowed to stand at 70° C. for 20 minutes. Next, the entire contents of the plastic bag were filled in the stainless steel tank so as to be uniform, and the contents were placed in a blower rack dryer at 130° C., and dried for 2 hours. Since the granulated product is solidified by drying, it was pulverized with a spoon twice during drying, and after the drying was completed, it was passed through a sieve with a mesh opening of 2000 μm to produce a granulated product (first component).

Measure 118.70 g of the obtained granules (the first component), 5.27 g of a solid mixture of acetic acid and sodium acetate with a molar ratio of acetic acid:sodium acetate of 1:1 (the second component), 26.25 g of glucose ( The second component), after fully mixing in a plastic bag, put into a moisture-proof packaging material containing an aluminum laminate layer and sealed to obtain a solid hemodialysis agent A.

Comparative Example 1 928.8 g of sodium chloride, 25.3 g of potassium chloride, and 18.0 g of magnesium chloride hexahydrate were respectively weighed, put into separate plastic bags to seal them, and heated to 70° C. using an air-supplied tray dryer. After heating, these raw materials and 18.0 g of purified water were placed in a plastic bag and sealed, and after being thoroughly mixed, they were placed in an air-supplied tray dryer again and allowed to stand at 70° C. for 20 minutes. Next, the entire contents of the plastic bag were filled in the stainless steel tank so as to be uniform, and the contents were placed in a blower rack dryer at 130° C., and dried for 2 hours. Since the granulated product is solidified by drying, it was pulverized with a spoon twice during drying, and after the drying was completed, it was passed through a sieve with a mesh opening of 2000 μm to produce a granulated product (first component).

Measure 118.70 g of the obtained granulated product (first component), 5.27 g of a solid mixture of acetic acid and sodium acetate whose molar ratio of acetic acid:sodium acetate is 1:1 (second component), 26.25 g of glucose ( The second component), after fully mixing in a plastic bag, put into a moisture-proof packaging material containing an aluminum laminate layer and sealed to obtain a solid hemodialysis agent A.

Comparative Example 2 Measure 928.8g of sodium chloride, 25.3g of potassium chloride, 28.2g of calcium chloride dihydrate, and 18.0g of magnesium chloride hexahydrate, respectively, put them into separate plastic bags to seal them, and use an air supply pan Heat the rack desiccator to 70 °C. After heating, these raw materials and 18.0 g of purified water were placed in a plastic bag and sealed, and after being thoroughly mixed, they were placed in an air-supplied tray dryer again and allowed to stand at 70° C. for 20 minutes. Next, the entire contents of the plastic bag were filled in the stainless steel tank so as to be uniform, and the contents were placed in a blower rack dryer at 130° C., and dried for 2 hours. Since the granulated product is solidified by drying, it was pulverized with a spoon twice during drying, and after the drying was completed, it was passed through a sieve with a mesh opening of 2000 μm to produce a granulated product (first component).

Measure 118.70 g of the obtained granulated product (first component), 5.27 g of a solid mixture of acetic acid and sodium acetate whose molar ratio of acetic acid:sodium acetate is 1:1 (second component), 26.25 g of glucose ( The second component), after fully mixing in a plastic bag, put into a moisture-proof packaging material containing an aluminum laminate layer and sealed to obtain a solid hemodialysis agent A.

2. The evaluation of the agent A for hemodialysis was carried out by the following method. The concentration of volatilized acetic acid after 3 months and 5 months, the solidification and coloring were confirmed, and the pH and the amount of 5-HMF when the concentrated A solution was prepared 35 times were measured.

(1) Determination of volatilized acetic acid concentration Assemble the detection tube into the bag containing each agent A for hemodialysis, pass a certain amount of sample gas into the detection tube for acetic acid measurement, and use a detection tube type gas analyzer (manufacturer : GASTEC, model: GV-100S) to measure the concentration of volatile acetic acid.

(2) Confirmation of solidification and coloration The presence or absence of solidification and coloring was confirmed in the bag containing each agent A for hemodialysis by visual inspection. The so-called solidification refers to a state in which fluidity is lost due to changes in the contents, and it becomes a state of moisture.

(3) Measurement of pH and 5-HMF Each agent A for hemodialysis was dissolved in purified water, and a 35-fold concentrated solution was prepared as an aqueous solution that was concentrated to 35 times the concentration of each component in the final prepared dialysate. A liquid. Specifically, a 35-fold concentrated solution A was prepared by dissolving the total amount of each hemodialysis agent A in purified water to prepare 500 mL. For each 35-fold concentrated solution A, the pH was measured at a liquid temperature of 25°C using a pH meter (manufacturer: Horiba, Ltd., model: F-73). The amount of 5-hydroxymethylfurfural (hereinafter referred to as 5-HMF), which is a decomposition product of glucose, was measured for the absorption of 5-HMF on the liquid filtered with a 0.2 μm filter using a spectrophotometer. Absorbance (Abs) at wavelength (wavelength 284nm).

The results are shown in Tables 3 to 7. As a result, in the case of mixing: the granulated product (first component) containing magnesium chloride and potassium chloride, and acetic acid and acetate (second component) (Comparative Examples 1 and 2), as As the storage period elapsed, the increase in the concentration of volatile acetic acid, the solidification, the coloration, and the decomposition of glucose became conspicuous. On the other hand, in the case of mixing: the granulated product (first component) containing only one of magnesium chloride or potassium chloride and calcium chloride, and acetic acid and acetate (second component) (Example 1 and 2), even after being stored for 5 months, the increase in the concentration of volatilized acetic acid can be sufficiently suppressed, and further, the increase in pH at the time of curing, coloring, and dissolving in water, and the decomposition of glucose can be sufficiently suppressed.

[table 3]

[Table 4]

[table 5]

[Table 6]

[Table 7]

Test Example 2 1. Preparation of solid hemodialysis agent A Example 3 Put 1000 kg of sodium chloride, 33.4 kg of calcium chloride dihydrate, 22.3 kg of magnesium chloride hexahydrate, and an appropriate amount of purified water into a Nauta mixer ( Nautamixer) (manufacturer: Hosokawa Micron Co., Ltd., model: DBX-5000RW) and mixed for 30 minutes to obtain granules. Subsequently, the granulated material was continuously fed to the vibrating screen, and the discharged granulated material was continuously conveyed. After continuous drying at a drying temperature of 155°C, it was cooled to produce a granulated product (first component).

115.70 g of the obtained granules (the first component), 5.27 g of a solid mixture of acetic acid and sodium acetate in a molar ratio of acetic acid:sodium acetate of 1:1 (the second component), and 3.0 g of potassium chloride were measured (Second component), after being sufficiently mixed in a plastic bag, a moisture-proof packaging material containing an aluminum laminate layer was placed and sealed to obtain a solid hemodialysis agent A.

Comparative Example 3 Put 1000 kg of sodium chloride, 28.9 kg of potassium chloride, 33.4 kg of calcium chloride dihydrate, 22.3 kg of magnesium chloride hexahydrate, and an appropriate amount of purified water into a Nauta mixer (manufacturer: Hosokawa Micron Co., Ltd., Model: DBX-5000RW) and mixed for 30 minutes to obtain granules. Subsequently, the granulated material was continuously fed to the vibrating screen, and the discharged granulated material was continuously conveyed to the dryer. After continuous drying at a drying temperature of 155°C, it was cooled to prepare a granulated product (first component).

Measure 118.70 g of the obtained granulation (the first component), 5.27 g of a solid mixture of acetic acid and sodium acetate with a molar ratio of acetic acid:sodium acetate of 1:1 (the second component), and put them in a plastic bag. After mixing, a moisture-proof packaging material containing an aluminum laminate layer was placed and sealed to obtain a solid-state hemodialysis agent A.

2. Evaluation of agent A for hemodialysis (1) Content measurement of granulated material (1st component) 115.72 g and 118.72 g of granulated material (1st component) used in Example 3 and Comparative Example 3 were measured respectively , dissolved in water, and the total amount was made 500 mL to obtain the respective granulated concentrates. The content of each main component was measured with respect to these granulated material concentrates by liquid ion chromatography.

The results are shown in Table 8. As a result, in the granulated material (1st component) produced in Example 3 and Comparative Example 3, the expected electrolyte content was confirmed.

[Table 8]

(2) Measurement of volatilized acetic acid concentration, confirmation of solidification and coloration, and measurement of pH For the hemodialysis agent A of Example 3 and Comparative Example 3, respectively: at the beginning and at the time of storage at 40°C/75%RH The measurement results were stored for 1 month, the volatile acetic acid concentration was measured after 5 days of storage at 50°C (no humidity control), the curing and coloring were confirmed, and the pH and 5-HMF amount when the concentrated solution A was prepared 35 times were measured. The specific measurement conditions were the same as those of Example 1 above.

The results are shown in Tables 9 to 11. As a result, in the case of mixing: the granulated product (first component) containing magnesium chloride, potassium chloride and calcium chloride, and acetic acid and acetate (second component) (Comparative Example 3), after storage , the increase of the concentration of volatile acetic acid, curing, and coloring become remarkable. On the other hand, in the case (Example 3) of mixing: the granulated product (1st component) containing magnesium chloride and calcium chloride, and potassium chloride, acetic acid, and acetate (2nd component), Even after storage, the increase in the concentration of volatilized acetic acid can be sufficiently suppressed, and further, the increase in pH at the time of curing, coloring, and dissolving in water can be sufficiently suppressed.

[Table 9]

[Table 10]

[Table 11]

Test Example 3 1. Preparation of solid agent A for hemodialysis Example 4 486 kg of the granulated product (1st component) used in Example 3, 12.4 kg of potassium chloride, 21.5 kg of acetic acid: sodium acetate molar A solid mixture of acetic acid and sodium acetate in a ratio of 1:1, and 106.4 kg of glucose were placed in a Nauta mixer (manufacturer: Hosokawa Micron Co., Ltd., model: DBX-5000RW) and mixed for 60 minutes, then discharged, and weighed 150.2 g , put into a moisture-proof packaging material containing an aluminum laminate layer and sealed to obtain agent A for hemodialysis.

Comparative Example 4 581 kg of the granulated product (1st component) used in Comparative Example 3, 25.7 kg of a solid mixture of acetic acid and sodium acetate, and 127.2 kg of glucose were placed in a Nauta mixer (manufacturer: Hosokawa Micron Co., Ltd. , Model: DBX-5000RW) after mixing for 60 minutes, after discharging, measuring 150.2g, placing it into a moisture-proof packaging material containing an aluminum laminate layer and sealing to obtain agent A for hemodialysis.

2. Evaluation of agent A for hemodialysis For the agent A for hemodialysis of Example 4 and Comparative Example 4, respectively, the measurement results at the beginning of storage at 40°C/75% RH and for one month were carried out. , and measured the volatile acetic acid concentration after 5 days of storage at 50°C (without humidity control), confirmed solidification and coloration, and measured the pH and 5-HMF amount when the concentrated A solution was made 35 times. The specific measurement conditions were the same as those of Test Example 1 described above.

The results are shown in Tables 12 to 14. As a result, in the case of mixing: the granulated product (first component) containing magnesium chloride, potassium chloride, and calcium chloride, and acetic acid and acetate (second component) (Comparative Example 4), the After storage, the concentration of volatilized acetic acid increased, solidification, coloration, increase in pH when dissolving in water, and decomposition of glucose became remarkable. On the other hand, in the case of mixing: the granulated product (1st component) containing magnesium chloride and calcium chloride, and potassium chloride, acetic acid, and acetate (2nd component) (Example 4) , even after storage, the increase in the concentration of volatilized acetic acid can be sufficiently suppressed, and further, the increase in pH at the time of curing, coloring, and dissolving in water, and the decomposition of glucose can be sufficiently suppressed.

[Table 12]

[Table 13]

[Table 14]

(none)

Claims (25)

A solid hemodialysis agent A, which is a solid hemodialysis agent A comprising a first component and a second component; wherein the first component contains magnesium chloride and calcium chloride, and does not contain chloride The granulated product of potassium contains acetic acid, acetate and potassium chloride as the second component. The solid agent A for hemodialysis according to claim 1, which contains acetic acid and an alkali metal acetate salt as the acetic acid and the acetate salt. The solid-state agent A for hemodialysis according to claim 1 or 2, which contains an alkali metal diacetate salt as the aforementioned acetic acid and acetate. The solid-state agent A for hemodialysis according to claim 1 or 2, which contains a higher hypoacetate compound as the aforementioned acetic acid and acetate. The solid agent A for hemodialysis according to claim 1 or 2, wherein the first component and/or the second component contains sodium chloride. The solid-state agent A for hemodialysis according to claim 1 or 2, wherein the first component contains sodium chloride. The solid-state hemodialysis agent A according to claim 1 or 2, wherein the first component and/or the second component contains glucose. The solid A preparation for hemodialysis according to claim 1 or 2, wherein the second component contains glucose. A 2-dose form hemodialysis agent, comprising: the solid-state hemodialysis agent A according to any one of claims 1 to 8, and a hemodialysis agent B comprising sodium bicarbonate. A 3-dose form hemodialysis agent, comprising: no Solid state hemodialysis agent A as shown in any one of claims 1 to 4, 7 and 8 of sodium chloride, hemodialysis agent S containing sodium chloride, and hemodialysis agent B containing sodium bicarbonate agent. A method for producing a solid agent A for hemodialysis, comprising a first step and a second step; wherein the first step is to prepare a granulated product containing magnesium chloride and calcium chloride and not containing potassium chloride, the first step The second step is to obtain a solid hemodialysis agent A, which contains the granulated product obtained in the first step, and acetic acid, acetate and potassium chloride. A solid A agent for hemodialysis, which is a solid A agent for hemodialysis comprising a first component and a second component; wherein the first component is a granulated product, and the granulated product contains only magnesium chloride One of potassium chloride and calcium chloride contains neither acetic acid nor acetate, and the second component contains acetic acid and acetate. The solid agent A for hemodialysis according to claim 12, wherein the first component contains magnesium chloride. The solid agent A for hemodialysis according to claim 12 or 13, wherein the first component contains magnesium chloride, and the second component contains potassium chloride. The solid agent A for hemodialysis according to claim 12, wherein the first component contains potassium chloride, and the second component contains magnesium chloride. The solid A preparation for hemodialysis according to claim 12 or 13, which contains acetic acid and an alkali metal acetate salt as the acetic acid and the acetate salt. The solid A agent for hemodialysis according to claim 12 or 13, which comprises an alkali metal diacetate as the aforementioned acetic acid and acetate. The solid-state agent A for hemodialysis according to claim 12 or 13, which comprises a homoacetate compound as the aforementioned acetic acid and acetate. The solid agent A for hemodialysis according to claim 12 or 13, wherein the first component and/or the second component contains sodium chloride. The solid A preparation for hemodialysis according to claim 12 or 13, wherein the first component contains sodium chloride. The solid A preparation for hemodialysis according to claim 12 or 13, wherein the first component and/or the second component contains glucose. The solid A preparation for hemodialysis according to claim 12 or 13, wherein the second component contains glucose. A 2-dose type hemodialysis agent comprising: the solid-state hemodialysis agent A according to any one of claims 12 to 22, and a hemodialysis agent B comprising sodium bicarbonate. A 3-dose form hemodialysis agent, comprising: a solid-state hemodialysis agent A as shown in any one of claims 12 to 18, 21 and 22 without sodium chloride, and a sodium chloride-containing hemodialysis agent Agent S, and Agent B for hemodialysis containing sodium bicarbonate. A method for producing a solid agent A for hemodialysis, comprising the first step and the second step; Wherein, the first step is to prepare a granulated product, the granulated product contains only one of magnesium chloride and potassium chloride, calcium chloride, and neither acetic acid nor acetate, the second step is to obtain solid Agent A for hemodialysis, the solid agent A for hemodialysis contains the granulated product obtained in the above-mentioned first step, acetic acid and an acetate salt.