JP2005194199A - Solid dialysis agent and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a solid dialysis agent to which glucose is adhered and which can give an excellent effect that the glucose is uniformly dispersed. <P>SOLUTION: This solid dialysis agent is characterized by adhering the glucose to the surfaces of the granules of a solid dialysis electrolyte comprising an electrolytic component and a pH adjusting agent. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a dialysis preparation for use in hemodialysis therapy for patients with renal failure, and particularly to a solid dialysis agent comprising an electrolyte component, a pH adjuster and glucose, and a method for producing the same.

Dialysis fluids used in recent hemodialysis treatments have been changed from conventional acetic acid dialysis fluids to bicarbonate dialysis fluids that have less burden on patients. However, in bicarbonate dialysate, bicarbonate ions react with calcium ions and magnesium ions to produce insoluble compounds (metal carbonates such as calcium carbonate and magnesium carbonate), making it difficult to make a single agent. . Therefore, an electrolyte component containing calcium ions and magnesium ions, a concentrated solution “A agent” containing glucose and a pH adjusting agent added as necessary, and a powder “B agent” made of sodium bicarbonate sodium bicarbonate. The two-dialysis agent is widely used.
However, this concentrated liquid “agent A” is usually filled with about 5 to 15 L of concentrated liquid in a polyethylene container. From its size and weight, transportation costs, hospital storage space, disposal method after use, etc. Is a problem.
Therefore, as a means for solving these problems, pulverization of the agent A has been considered (for example, Japanese Patent Publication No. 57-88116) and has already been commercialized.
However, solid dialysis agents currently on the market tend to generate dust when the preparation is put into a dissolution apparatus, and there is a problem that the odor of acetic acid used as a pH adjuster at that time is quite strong. It is also a cause of worsening the work environment in the medical field. This is caused by the method of adding acetic acid as a pH adjuster, etc., when the particles of the preparation are broken during production, transportation and storage.
In addition, dirt on the electrolyte particles itself, which is the core of the solid preparation, and dirt that may be caused by contamination in the solidification manufacturing process may adhere to the dissolution apparatus. For example, a dry granulation method in which a solid electrolyte for dialysis is stirred and mixed, pulverized, and granulated as in Japanese Patent Application Laid-Open No. 2-311418 is likely to cause such a problem.
Furthermore, in the case of this invention, since glucose is mixed at the time of granulation, there exists a problem that it is not mixed uniformly. In addition, the modification of glucose by making glucose and other components the same granulated product is also a problem.
On the other hand, Japanese Patent Application Laid-Open No. 6-237991 discloses a multilayer solid dialysate solidified in a tablet shape with a multilayer structure. In such a method, dust is not scattered and handling is easy, but the manufacturing process is complicated and the manufacturing cost is high, and the melting apparatus is not realistic unlike the conventional one.
Japanese Patent Publication No.57-88116 (Claims) Japanese Patent Laid-Open No. 2-311418 (Claims) Japanese Patent Laid-Open No. 6-237991 (Claims)

  In order to solve these problems, the inventors of the present application, as a result of intensive studies, in a solid dialysis agent comprising an electrolyte component, a pH adjuster and glucose used in hemodialysis therapy for renal failure patients. The present invention was completed by discovering that a solid dialysis agent with good content uniformity, excellent solubility, and uniform production of glucose containing glucose was obtained.

  The present invention relates to a solid dialysis agent in which glucose is adhered to the surface of a granulated product of a solid electrolyte for dialysis comprising an electrolyte component and a pH adjuster, and a method for producing the same.

This invention of this application can acquire the outstanding effect that glucose is uniformly disperse | distributed by attaching glucose.
In the invention of this application, the raw materials are uniformly mixed as a pretreatment for the granulation step, and kneaded and granulated with a water and / or ethanol solution of calcium chloride and / or magnesium chloride as a binder liquid, It is possible to provide a method for producing a solid dialysis agent that is excellent in uniformity and solubility, can significantly reduce granulation time depending on the concentration of the binder liquid and the amount of the binder solution added, and can be mass-produced.

Glucose is preferably attached to the granulated product immediately after granulation or at 30 to 80 ° C., particularly 35 to 50 ° C.
The adhesion is preferably performed by adding glucose to the granulated material and kneading.
By doing in this way, glucose can be made to adhere uniformly to the circumference | surroundings of the granulated material of electrolyte and a pH adjuster.
Glucose can also be attached after impregnating a liquid pH adjuster into an electrolyte granule containing an electrolyte and, if necessary, a pH adjuster.
By doing in this way, especially the acetic acid which is a pH adjuster, and glucose do not contact directly, Therefore Glucose deterioration can be prevented.

In the invention of this application, the dialysis agent is an A component consisting of an electrolyte component and glucose, and after being diluted and mixed with an appropriate concentration of B agent consisting of sodium bicarbonate, it is used as a perfusion solution for hemodialysis. . The blending amount of each component at this time is preferably the following concentration.
Na ⁺ 130-145 mEq / L
K ⁺ 0-4 mEq / L
Ca ⁺⁺ 0-4 mEq / L
Mg ⁺⁺ 0-2 mEq / L
Cl ^- 55-135 mEq / L
HCO ₃ ^- 20~45 mEq / L
Acetate ion 0-20 mEq / L
Citrate ion 0-10 mEq / L
Glucose ~ 2.0 g / L
(When dissolved in a certain amount of water and / or ethanol, the solid dialysis agent is Na + 90-140 mmol K + 0-4 mmol Ca ⁺⁺ 0.5-2.2 mmol Mg ⁺⁺ 0.2-1.0 mmol Cl ^- is preferably 6 to 15 mmol glucose 4-12 mM ^- 90 to 140 mmol CH ₃ COO.
Further, sodium bicarbonate ^Na + 15-40 mmol HCO ₃ ^- is preferably from 15 to 40 millimoles. )

  Particularly preferred electrolyte components are sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate or sodium citrate, but other electrolyte components can be used without particular limitation as required. Moreover, as a pH adjuster, what is generally used, such as an acetic acid, lactic acid, hydrochloric acid, a citric acid, malic acid, may be sufficient, but an acetic acid and a citric acid are especially preferable. At that time, it is more preferable to use sodium acetate as an electrolyte component in the case of acetic acid and sodium citrate in the case of citric acid.

  In this invention, calcium chloride and / or magnesium chloride is dissolved in water and / or ethanol and used as a binder liquid. At this time, it is dissolved in about 0.2 to 20% of the total weight of the raw material, more preferably about 0.2 to 10%, and further preferably about 0.2 to 5% of water and / or ethanol. Good. This is because when the water content of the binder is about 0.2% or less, the adhesion and aggregation action of each particle is small and granulation is difficult to proceed, while the water content of the binder is 20% or more. In this case, the powder is wetted in the granulator and becomes cocoon-like, making granulation difficult. In addition, this total raw material weight is a weight that combines all of the components used for granulation among the electrolyte component and the pH adjuster that are constituent components of the dialysis agent.

  Also, depending on the total weight of the raw material, the amount of water and / or ethanol decreases, and when calcium chloride and magnesium chloride are dissolved, it becomes saturated, and if the total amount cannot be dissolved, either calcium chloride or magnesium chloride, Alternatively, a part of calcium chloride and magnesium chloride can be dissolved and used as a binder liquid. In that case, the remaining calcium chloride and / or magnesium chloride not dissolved in the binder liquid is pulverized together with other components and granulated.

  The addition method of the binder liquid is to prevent the formation of coarse particles and to make the preparation excellent in content uniformity, so that the binder liquid should be spread evenly, for example, by spraying on the powder being stirred and mixed. The method of dropping is preferred. Thus, by adding deliquescent calcium chloride and / or magnesium chloride as a binder solution, a solid dialysis agent having excellent content uniformity can be produced. In addition, by dissolving in water and / or ethanol of about 0.2 to 20% of the total weight of the raw material, the water and / or ethanol content can be reduced and the drying time can be shortened. Less formulation.

In the invention of this application, it is possible to incorporate a crushing step in which each component is crushed so as to have a particle size of about 1.5 mm or less, and aligned to a certain size. As a result, since the raw materials can be uniformly mixed in the next granulation step, a dialysis agent excellent in content uniformity can be finally produced. In this crushing step, the components other than the calcium chloride and / or magnesium chloride used as a binder among the electrolyte component and the pH adjuster, which are constituent components of the dialysis agent, are dissolved so as to become particles of about 1.5 mm or less. Crush. If the apparatus used in that case can pulverize each component to a size of about 1.5 mm or less, a general pulverization type granulator can be used.
The granular material preferably has an average particle size of 12 to 100 mesh with a standard sieve.

In this crushing step, only sodium chloride may be crushed to about 1.5 mm or less. In other words, the ingredients without sodium chloride are granulated, sized and dried, and after the granulated product of dialysis agent without sodium chloride is produced, the crushed sodium chloride is mixed or packaged to prepare the dialysis agent. You can also Among the components contained in the dialysis agent of the present invention, sodium chloride accounts for about 60 to 80% of the total weight of the raw material, so that the granule without sodium chloride can reduce the scale of the apparatus and the production cost. Reduction and manufacturing efficiency can be increased.
Furthermore, when packaging, for example, by putting a granulated product without sodium chloride and sodium chloride into a bag separated into a plurality of chambers by an inner partition, it can be opened at once even when opened, It is possible to prevent forgotten or wrong insertion and provide a preparation with good operability.

Next, in the granulation step, kneading, granulating and drying are performed while adding a binder liquid to the crushed components. The apparatus used in this granulation step may be a general mixing granulator capable of uniformly kneading and granulating using the pulverized components and the binder liquid, for example, a kneader.
Thereafter, in order to increase the drying efficiency, it is preferable to size the particles to a certain size. The apparatus used here may be a general one, for example, a crushing type granulator, a classifier or the like.
Next, the drying apparatus used in the drying step may be a general batch type or continuous type, and examples thereof include a fluidized bed dryer and a vacuum dryer.
Thereafter, in order to prepare the dried granulated product in a desired size, it is preferable to perform granulation. The apparatus used here may be a general one, for example, a crushing type granulator, a classifier or the like.

  In the invention of this application, when the pH adjuster is a liquid such as acetic acid, after the drying step, the granulated product made of the electrolyte and the pH adjuster are added while being mixed using a mixing device, and the odor is sucked. By this, the intense acetic acid odor at the time of throwing into a melt | dissolution apparatus can be reduced. In this case, a general mixing device may be used, and examples thereof include W type, V type, and ribbon type mixers. The suction is performed using, for example, a vacuum pump, a blower pump, or the like. The granulated product produced by the invention of this application is porous and absorbs these pH adjusters well.

  When the pH adjusting agent is a solid such as citric acid, it is added as a raw material in the mixing step. The pH adjusting agent can be added by a method of adding as a liquid or a method of impregnating the granulated product by mixing with the granulated product before or after the granulation step.

In the invention of the present application, glucose is mixed with the granulated product, adhered to the granulated product, and dried. Moreover, after impregnating a granulated material with a pH adjuster, glucose is mixed and made to adhere and it dries.
When glucose is attached, a method in which glucose is not heated, preferably 20 to 60 ° C., particularly preferably 30 to 50 ° C., is mixed with 5-hydroxymethylfurfural (5-HMF) which is a glucose degradation product. ) And the like are suppressed.

The container packaging material of this invention is preferably one that prevents permeation of water vapor and gas. For example, it is desirable to use a material having a moisture permeability (40 ° C., 90% RH) of 1.0 g / cm ² · 24 hr or less. Examples of the material include PET / glass vapor-deposited PET / PE, PET / aluminum oxide / nylon, PET / SiOx / CPP, PET / SiOx / nylon / CPP, and OPP / SiOx / CPP.

Hereinafter, the present invention will be described in detail by way of examples.

“5HMF measurement sample preparation”
Sodium chloride (average particle size 350 μm) 12.62 kg, potassium chloride (average particle size 350 μm) 0.30 kg, sodium acetate (average particle size 400 μm) 1.50 kg vertical granulator (VG-25 type, POWREC Co., Ltd.) ) 0.37 kg of calcium chloride and 0.21 kg of magnesium chloride dissolved in 0.375 kg (2.5%) of water and kneaded and granulated. This operation was repeated three times to obtain about 45 kg of a granulated product. After the granulated product was dried, 40 kg of the granulated product, 625 g of acetic acid and 5.4 kg of glucose (average particle size 200 μm) were mixed with ribocorn (RM-50 type, Okawara Seisakusho Co., Ltd.) to which glucose adhered. A dialysis agent (added after glucose) was produced.
(Comparative Example 1)
Vertical granule containing sodium chloride (average particle size 350 μm) 11.12 kg, potassium chloride (average particle size 350 μm) 0.27 kg, sodium acetate 1.32 kg (average particle size 400 μm), glucose (average particle size 200 μm) 1.79 kg It was mixed with a mixer (VG-25 type, POWREC Co., Ltd.). To this mixture, 0.33 g of calcium chloride and 0.18 g of magnesium chloride were added after being dissolved in 0.33 kg (2.2%) of water, and kneaded and granulated. 2331 g of the granulated product put in a dryer and dried was put in a V-type mixer and mixed with 38 g of acetic acid. This was designated as Comparative Example 1 (addition of glucose tip).

Measurement Method 59.6 g of this sample was dissolved to make 200 mL. 10 mL of this liquid was taken, and the absorbance at a wavelength of 284 nm was measured for the liquid to which 4 mL of water was added.
The measurement results are as follows.

Sodium granule (average particle size 350 μm) 37.86 kg, potassium chloride (average particle size 350 μm) 0.90 kg, sodium acetate (average particle size 400 μm) 4.50 kg is vertical granulator (VG-100 type, POWREC Co., Ltd.) ) 1.11 kg of calcium chloride and 0.63 kg of magnesium chloride were dissolved in 1.125 kg (2.5%) of water and added, and kneaded and granulated. After this granulated product is dried, 40 kg of the granulated product, 652 g of acetic acid and 5.4 kg of glucose (average particle size 200 μm) are adjusted to a product temperature of 40 ° C. The resulting mixture was designated Prototype 1 (added after glucose).

Measurement method The results of measuring glucose content by HPLC using a solution of 59.6 g of this sample dissolved in water to 200 mL are shown in the table. In Example 2, glucose was uniformly mixed.

  The present invention relates to a dialysis preparation for use in hemodialysis therapy for patients with renal failure, particularly a solid dialysis agent comprising an electrolyte component, a pH adjuster and glucose, and a method for producing the same, wherein glucose is uniformly dispersed. An agent for solid dialysis can be provided.

Claims (13)

A solid dialysis agent, wherein glucose is adhered to the surface of a granulated product of a solid electrolyte for dialysis comprising an electrolyte component and a pH adjuster. 2. The method for producing a solid dialysis agent according to claim 1, wherein the electrolyte component and the pH adjuster are granulated, and then glucose is adhered to the granulated product. 3. The method for producing a solid dialysis agent according to claim 2, wherein the granulation is performed by adding a binder solution. The method for producing a solid dialysis agent according to claim 3, wherein the binder solution is a solution in which all or part of calcium chloride and / or magnesium chloride is dissolved in water and / or ethanol. The solid according to claim 3 or 4, wherein the binder liquid is obtained by dissolving calcium chloride and / or magnesium chloride in water and / or ethanol of about 0.2 to 20% of the total weight of the raw material. A method for producing a dialysis agent. The solid according to claim 3 or 4, wherein the binder liquid is obtained by dissolving calcium chloride and / or magnesium chloride in water and / or ethanol of about 0.2 to 5% of the total weight of the raw material. A method for producing a dialysis agent. The method for producing a solid dialysis agent according to claim 1, wherein the binder liquid contains all or part of the pH adjusting agent. 2. The solid dialysis agent according to claim 1, wherein all or part of the pH adjuster is impregnated in an electrolyte or a granulated product of an electrolyte containing the pH adjuster as necessary, and glucose is then adhered. Manufacturing method. Each component is a particle | grain of about 1.5 mm or less, The manufacturing method of the agent for solid dialysis in any one of Claims 1-8 characterized by the above-mentioned. About 1.5 mm or less of sodium chloride is mixed with the solid dialysis agent in which glucose is adhered to the surface of the granulated product of the solid electrolyte for dialysis comprising electrolyte components other than sodium chloride and a pH adjuster. A solid dialysis agent. The method for producing a solid dialysis agent according to any one of claims 2 to 9, wherein the electrolyte contains no sodium chloride. It is characterized by comprising a solid dialysis agent in which glucose is adhered to the surface of a granulated product of a solid electrolyte for dialysis comprising an electrolyte component other than sodium chloride and a pH adjusting agent, and sodium chloride of about 1.5 mm or less. A solid dialysis agent. A preparation for dialysis comprising the solid dialysis agent according to claim 1, 10 or 12, and sodium hydrogen carbonate.