JP2986810B2 - Dialysis agent and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial application] The present invention relates to a dialysis agent, in particular, a granular material which is free from a precipitate upon reaction when dissolved when used, is homogeneous, has good composition stability and good flowability. The present invention relates to a granulated dialysis agent which is easily soluble when it is dissolved and dissolved.

[Related Art] A dialysis agent is an agent for preparing a dialysate. The dialysate is used to remove the waste of body fluids and to supplement the necessary components in the blood, instead of the functions originally performed by the kidneys by artificial kidneys (hemodialysis, peritoneal dialysis, etc.). A baking soda dialysate using baking soda as an agent has attracted attention because it is physiologically effective. As the sodium bicarbonate dialysate, one having the following electrolyte ion composition is used.

Na ⁺ 120~150mEp / K ⁺ 0.5~3.0 〃 Ca ⁺⁺ 1.5 to 4.5 〃 Mg ⁺⁺ 0 to 2.0 〃 Cl ^- 90 to 135 〃 CH ₃ COO ^- 5~ 35 〃 HCO ₃ ^-. 20 to 35 〃 glucose 0 250g / normal baking soda dialysate is about 2.5kg of required electrolytes other than baking soda
About 10 volumes of stock solution A
And divided into this and an aqueous solution of sodium bicarbonate as an alkaline agent,
At the time of dialysis, both are mixed and the total amount is diluted to 350 before use. Baking soda may be stored or transported in powder form and dissolved immediately before use.

[Problems to be Solved by the Invention] However, when the aqueous solution of sodium bicarbonate and other electrolyte components are prepared in advance as described above, even if this is a concentrated stock solution, the volume and weight become considerable. However, there is a disadvantage that storage and transportation are inconvenient.

In order to avoid this, when handling as mixed powder, the particle shape and specific gravity of each powder are different, so the components are biased during storage and transportation, and the total amount of the storage unit should be reduced when dissolving. Unless the components are dissolved at once, a solution having a desired composition cannot be obtained. Even when the entire amount of the storage unit was dissolved, each had a disadvantage that they did not dissolve homogeneously and tended to become a heterogeneous liquid. Alternatively, during storage or the like, sodium bicarbonate and a calcium or magnesium component react with each other to easily generate a hardly soluble carbonate.

Further, in the case of baking soda, it has been considered that when it is powdered, it generally has poor fluidity, is difficult to handle, and has a disadvantage of poor solubility.

[Means for Solving the Problems] The present invention eliminates the drawbacks of these conventional dialysis agents, is advantageous for storage and transport, and can easily obtain a dialysate. It was done with the purpose of obtaining.

 The configuration of the present invention is as follows.

(1) a mixture of a granulated product (agent A) comprising a group containing a calcium component and not containing baking soda and a granulated product (agent B) comprising a group containing baking soda and containing no calcium component, Is a homogeneous granulated product comprising at least one electrolyte component selected from sodium chloride, potassium chloride and sodium acetate and sodium bicarbonate, and the particle size of the agent A and the agent B is the average of those having a large average particle size. A dialysis agent, wherein the ratio of the average particle size of the small agent to the particle size is 0.9 or more.

(2) The above (1), wherein the dissolution rate of the dialysis agent is within 3 minutes.
The dialysis agent according to the above.

(3) The dialysis agent according to the above (1) or (2), wherein the angle of repose of the dialysis agent is 50 degrees or less.

(4) At least one electrolyte component powder selected from sodium chloride, potassium chloride and sodium acetate and sodium bicarbonate powder are mixed by adding water so that the water content is 0.5 to 15% by weight, and granulated and dried. (1) to (1) to (4), wherein a granulated material (agent B) is produced by mixing the mixture with a granulated material (agent A) comprising a group containing a calcium component and not containing sodium bicarbonate.
The method for producing a dialysis agent according to any one of (3).

(5) The method for producing a dialysis agent according to (4), wherein the drying is performed in a carbon dioxide gas atmosphere.

In the present invention, the components contained in the dialysis agent are divided into two groups, agent A and agent B, each of which is granulated and then mixed.
The particle size of the A agent and the B agent must be controlled during granulation so that classification does not easily occur after mixing.
The particle diameters of the A agent and the B agent are preferably substantially the same, and the ratio of the average particle diameter of the smaller agent to the average particle diameter of the agent having the larger average particle diameter is preferably 0.9 or more. .

In the agent B of the present invention, the component that may be present together with baking soda is at least one electrolyte component that does not contain a calcium component. Examples of such an electrolyte component include sodium chloride, potassium chloride, sodium acetate, magnesium chloride, and the like. If necessary, other components such as glucose and urea are appropriately used unless the object of the present invention is inhibited. can do.

The agent B of the present invention may be one containing substantially only baking soda.

On the other hand, in the agent A, the electrolyte component composed of the calcium component is granulated together with these or other necessary components. At this time, the agent A and the agent B need to be granulated so as not to be classified. Usually, the calcium component is prepared as a chloride, and in the case of granules, the form of CaCl ₂ .2H ₂ O is stable. In addition, a small amount of additives such as acetic acid and glucose may be further added together with these as desired.

Further, the magnesium component can be blended with the agent B at the concentration used for the dialysis agent, but since it easily reacts with baking soda to form a hardly soluble solid, it is preferable to blend the magnesium component into the agent A together with the calcium component. Normally, the magnesium component is prepared as chloride, and in the case of granules, MgCl ₂・ 6H ₂ O
The shape is stable.

As a means for granulating the A agent and the B agent, each component can be appropriately mixed with water as powder and granulated using a suitable granulator. By adopting the following means, the solubility, particularly the solubility of sodium bicarbonate, can be effectively improved, the handling of the granular material is easy, the strength is sufficient, the powdering is difficult, and the uniformity is obtained. It is preferable because a granular material having good composition stability can be obtained. This method is particularly preferable for granulating the A agent and the B agent so that classification is unlikely to occur.

The particle size of the electrolyte component powder is adjusted, and the water content is 0.5 to 15% by weight.
Water is added to the mixture, and the mixture is sufficiently mixed, granulated by an extrusion granulator or the like, and then dried to obtain a granular product. It is appropriate that the particle diameter of the electrolyte component powder as a raw material to be used is 250 μm or less, preferably 180 μm or less, more preferably 100 μm or less. Particle size 250μ
If the ratio exceeds the above range, the mechanical strength of the granules as the final product becomes insufficient, and the granules are partially powdered and the dissolution rate is undesirably reduced. In addition, moisture is 0.5% by weight during granulation.
If the amount is less than 15%, the particle strength is low and the powder is easily powdered. On the other hand, if the amount exceeds 15% by weight, granulation may be difficult, so neither is preferable. The particle size of the particles thus granulated is suitably about 0.1 to 5 mm. If the particle size of the granular material is less than the above range, the fluidity is impaired, or the powder is scattered and becomes difficult to handle, and if it exceeds the above range, the mechanical strength of the particles decreases. Or dissolution may take too long.

When drying the granulated material, particularly the agent B, it is preferable to use a carbon dioxide gas atmosphere or an acetic acid gas atmosphere for the purpose of preventing decomposition of sodium bicarbonate and suppressing evaporation of acetic acid gas. When using an atmosphere of carbon dioxide gas or acetic acid gas, it is appropriate to employ a carbon dioxide gas concentration of about 5% or more and an acetic acid gas concentration of about 0.05 to 5%.

Drying is suitably performed at 30 to 90 ° C., and specific drying means include, for example, a band dryer, a disk dryer, a through-air dryer, a rotary dryer, and the like.
It is possible to obtain granules having high strength, high solubility, uniformity and good composition stability.

The granular material thus obtained has a dissolution rate (9.3 g of this granular material
The time required for the solution to become transparent when dissolved in 1000 ml of water at 25 ° C is less than 3 minutes, and the angle of repose (measured with a powder tester manufactured by Hosokawa Micron Co., Ltd.) is 50 degrees or less. Very good in handling such as solubility, fluidity and the like can be obtained. In addition, the packaging of these granular materials is sealed,
Decomposition, preferably by encapsulation with carbon dioxide,
Deterioration can be further prevented.

Thus, when the dialysis agent according to the present invention is used, it is supplied to the dialysate as an aqueous solution according to a conventional method. A comparison between the dialysis agent of the present invention and the dialysis agent according to the conventional method shows that, in the prior art, about 6% by weight of sodium bicarbonate was concentrated and diluted 27 times with water. Is mixed with 1 volume of the electrolyte component solution to obtain a dialysis solution. On the other hand, the present dialysis agent can be made into a dialysis solution simply by dissolving with 100 times water.

The dialysis agent of the present invention may contain a pH adjusting component such as acetic acid in advance for the purpose of adjusting the pH after dissolution. The pH adjusting component may be added to the dialysate after dissolution.

In the agent B of the present invention, the component that can be granulated together with baking soda is at least one of an electrolyte component that does not contain a calcium component. Of these, components that are required in large amounts are mainly granulated together with baking soda. It is effective to do. In this case, since the required amount of the electrolyte component containing calcium is relatively smaller than that of the other electrolyte components, the preparation of the agent A does not cause much inconvenience when used separately. As a form prepared separately, a powder form or a solution form may be used. For example, when preparing an electrolyte component containing calcium as an aqueous solution (chloride), it is generally appropriate to adopt a capacity of about 100 to 200 cc from the viewpoint of storage properties and transport. Even when the agent A is in the form of an aqueous solution, it is preferable to mix the magnesium component with the agent A.

Example 1 Example 1 Sodium bicarbonate, sodium chloride, potassium chloride and sodium acetate trihydrate, each ground to an average particle size of about 50 μm, were mixed in the following ratio, and 5% by weight of water was further added. And mixed.

NaHCO ₃ 27.072% by weight NaCl 62.155 KCl 1.995 CH ₃ COONa.3H ₂ O 8.778 500 g of particles having an average particle diameter of 400 μm were obtained from the mixture using a twin-screw granulator. Then, carbon dioxide concentration 20% and acetic acid gas
In an atmosphere containing 0.5% and adjusted to a temperature of 50 ° C., the particles were placed in a batch box dryer and dried for 3 hours. The obtained granules are granular, the average particle size is 0.4 mm, the angle of repose is 40 degrees, and has good fluidity,
The dissolution rate when dissolved in water at 25 ° C. was 1.5 minutes. Take 5 samples (9.3085g) arbitrarily from the above product,
Dissolved in water at 5 ° C. to a total volume of 1000 ml. The results are shown in Table 1.

From Table 1 above, it is clear that after collecting the granules at random, the calcium and magnesium components can be appropriately added to restore the dialysate having a very uniform composition for all five samples.

Next, the change over time due to long-term storage of the granulated product was examined. The obtained granules are hermetically packed and allowed to stand at room temperature. Immediately after production, 1 month, 3 months, 6 months and 12 months have elapsed, a predetermined amount (9.3085 g) was taken, and water at 25 ° C. To dissolve in a total volume of 1000 ml. About the obtained solution,
Table 2 shows the results obtained by assuming that the pH and each ion concentration immediately after the production were 100, and the deviation from this was determined.

According to Table 2, this granulated product is extremely stable over time.
It is clear that the dialysate can be restored to a substantially unchanged state immediately after production even after long-term storage.

Comparative Example 1 Sodium chloride, potassium chloride, calcium chloride, calcium chloride each pulverized to an average particle size of about 50 μm
The hydrate, magnesium chloride hexahydrate and sodium acetate trihydrate were mixed in the following ratio, and 5% by weight of water was further added and mixed.

NaCl 80.389 wt% KCl 2.580 〃 CaCl ₂・ 2H ₂ O 3.573 〃 MgCl ₂・ 6H ₂ O 2.104 〃 CH ₃ COONa ・ 3H ₂ O 11.354 500 kg was obtained. Next, the particles were placed in a batch box dryer under an atmosphere containing 0.5% acetic acid gas and adjusted to a temperature of 50 ° C., and dried for 3 hours. The obtained particles (referred to as “A agent”) are granular, have an average particle diameter of 0.45 mm, and have a repose angle of 40.
Degree and showed good fluidity.

On the other hand, 5% by weight
Water was added and mixed, and the mixture was granulated with a twin-screw granulator to give an average particle size of 45.
200 kg of 0 micron particles were obtained. Next, the particles were placed in a batch-type box dryer under an atmosphere adjusted to a temperature of 50 ° C. containing a carbon dioxide gas concentration of 20%, and dried for 3 hours. The obtained particles (referred to as agent B) were granular and had an average particle diameter of 0.45 mm, indicating good fluidity.

Next, the A agent and the B agent were mixed at a ratio of 2.856: 1 (weight ratio) to obtain 500 kg of a mixed powder. The obtained mixture of agent A and agent B (referred to as dialysis agent) has an angle of repose of 40 degrees, has good fluidity, and has a dissolution rate of 1 minute when dissolved in water at 25 ° C. there were. Table 3 shows the results obtained by arbitrarily taking five samples (9.7171 g) from the above dialysis agent and dissolving them in water at 25 ° C. in a total volume of 1000 ml.

From Table 3 above, it is clear that when the dialysis agent is randomly collected and then dissolved, the five samples can be reconstituted into a dialysate having a very uniform composition. Then
The temporal change of the dialysis agent according to the present invention due to long-term storage was examined. The obtained dialysis agent is hermetically packed and left at room temperature,
Immediately after production, one month, three months, six months, and 12 months later, a predetermined amount (9.7171 g) was taken and dissolved in water at 25 ° C. in a total volume of 1,000 ml. Table 4 shows the results obtained by assuming that the pH of the obtained solution and the respective ion concentrations immediately after the production were 100, and the deviation from this was obtained.

From Table 4, it is clear that this dialysis agent is extremely stable over time and can be restored to a dialysate substantially unchanged from immediately after production even after long-term storage.

[Effect of the Invention] The dialysis agent of the present invention can be easily dissolved in water to form a homogeneous aqueous solution, and a dialysate can be easily obtained. In addition, the present dialysis agent can be reduced in volume, and is advantageous for storage or transport without powdering during storage or formation of a hardly soluble compound. Furthermore, since it is excellent in fluidity, handling is easy.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-56-131515 (JP, A) JP-A-3-38527 (JP, A) JP-A-57-88116 (JP, A) US Patent 4,489,535 (US , A) Yoshinobu Nakai et al., “New Pharmaceutical Sciences”, 1987.4.1, Nanzando, pp. 115-116, edited by the Chemical Dictionary Editor's Committee, “Chemical Dictionary 5”, 1987.2.15. Kyoritsu Shuppan, 726 pages, Dictionary of Chemistry Dictionary, edited by the Dictionary of Chemistry 3, 1987.2.15. Kyoritsu Shuppan 810 pages (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 33/00 A61K 33/06 A61K 33/14 CA (ONLINE) WPIL (DERWENT)

Claims (5)

(57) [Claims] 1. A mixture of a granulated product comprising a group containing a calcium component and not containing baking soda (agent A) and a granulated product containing a group containing baking soda and containing no calcium component (agent B), The agent B is a homogeneous granulated product comprising at least one electrolyte component selected from sodium chloride, potassium chloride and sodium acetate and baking soda, and the particle diameters of the agent A and the agent B are large. A dialysis agent, wherein the ratio of the average particle size of the small agent to the average particle size of the agent is 0.9 or more. 2. The dialysis agent according to claim 1, wherein the dissolution rate of the dialysis agent is within 3 minutes. 3. The dialysis agent according to claim 1, wherein the angle of repose of the dialysis agent is 50 degrees or less. 4. Granulation of at least one electrolyte component powder selected from sodium chloride, potassium chloride and sodium acetate and sodium bicarbonate powder by adding water to a water content of 0.5 to 15% by weight. 4. A granulated product (agent B) is produced by drying and mixed with a granulated material (agent A) comprising a group containing a calcium component and not containing sodium bicarbonate.
The method for producing a dialysis agent according to any one of the above. 5. The method for producing a dialysis agent according to claim 4, wherein said drying is performed in a carbon dioxide gas atmosphere.