JPH06105906A - Dialysis agent - Google Patents

Abstract

PURPOSE:To provide the agent for dialysis which is in a powdery form advantageous for storage and transportation and does not discolor even after long-term preservation. CONSTITUTION:This agent for dialysis is prepd. by mixing a solid electrolyte and glucose component and the moisture in such mixture is <=2.0wt.%. sodium bicarbonate is used as an alkalinizer.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a dialysis agent for producing a dialysate.

[0002]

2. Description of the Related Art A dialysis agent is a drug for producing a dialysate. The dialysate replaces the function originally performed by the kidney by artificial kidney, hemodialysis, peritoneal dialysis, etc., and is used for removing waste products of body fluid and for supplementing necessary components in blood. Two types of dialysate are known, an acetic acid dialysate using sodium acetate as an alkalizing agent and a baking soda dialysate using sodium bicarbonate as an alkalizing agent.

For example, a baking soda dialysate having an electrolyte ion composition as shown below is used. Na ⁺ 120 to 150 mEq / l K ⁺ 0.5 to 3.0 mEq / l Ca ⁺⁺ 1.5 to 4.5 mEq / l Mg ^{++ 0 to} 2.0 mEq / l Cl ^- 90 to 135 mEq / l CH ₃ COO ^- 5 to 35 mEq ^{_{/ l HCO 3 - 20~ 35 mEq}} / l of glucose 0~2.5 g / l

Usually, a sodium bicarbonate dialysate is divided into a concentrated solution of necessary electrolytes and glucose components other than sodium bicarbonate and an aqueous sodium bicarbonate solution as an alkalizing agent, and both are mixed and diluted during dialysis. Baking soda may be stored or transported in powder form and dissolved immediately before use.

However, in the case where the solution of the electrolyte and glucose component is prepared in advance as described above, even if this solution is made into a concentrated stock solution, the volume and weight become considerable, and the solution is stored, transported or used. Is inconvenient to handle. In order to avoid this drawback, a dialysis agent that stores and transports the electrolyte and glucose components as powder is also known.

As the acetic acid dialysis agent, there is known a powdery one in which sodium acetate as a direct alkalizing agent is added as a powder to the same electrolyte and glucose components as the sodium bicarbonate dialysis agent.

[0007]

However, when the powder containing glucose is stored for a long period of time, a phenomenon in which glucose is deteriorated and colored yellow (hereinafter referred to as yellowing) occurs. Yellowing does not directly adversely affect the physiological effect of the dialysate, but the appearance of the dialysate exhibits a yellow color, which reduces the commercial value.

[0008]

Means for Solving the Problems The present inventor has conducted a detailed study on factors affecting the yellowing of glucose,
It was found that yellowing can be suppressed by controlling the amount of water in the dialysate to a specific range.

The present invention relates to a dialysis agent in which a solid electrolyte and a glucose component are mixed, and the water content in the mixture is 2.
A dialysis agent having a content of 0% by weight or less is provided.

In the present invention, the water content in each electrolyte component and glucose (hereinafter referred to as agent A) is 2.0% by weight or less, preferably 1.8% by weight or less, more preferably 1.3% by weight or less.
When the content is less than or equal to wt%, the progress of yellowing of the agent A can be suppressed within the limit. The water content in the dialysate can be measured, for example, by the Karl Fischer method of the Japanese Pharmacopoeia.

Here, as the electrolyte component, a conventional one can be used, for example, NaCl, KCl, CaC.
l ₂ , MgCl ₂ , salts such as sodium acetate, lactic acid,
Acids (pH adjusters) such as acetic acid and hydrochloric acid are used.

In the present invention, the case where the agent A is granulated is preferable because the fluidity is improved and the generation of dust can be suppressed.
The pore volume of the granulated product is preferably 0.03 to 0.2 cc / g. If the pore volume is less than 0.03 cc / g, the dissolution rate may slow down, which is not preferable. Pore volume is 0.2
If it exceeds cc / g, the strength of the granulated product may decrease and dust generation may appear, which is not preferable.

In the case of granulating the agent A, the respective components can be appropriately mixed in the form of powder with water and granulated using various granulators. The particle size of the electrolyte component powder is adjusted so that the water content is 1
Water is added to -25% by weight, mixed well, granulated by an extrusion granulator or the like, and dried to give a granular product. If the water content during granulation is less than 1% by weight, the particle strength will decrease and the powder will be pulverized and vice versa.
If it exceeds 25% by weight, granulation may be difficult, and therefore neither is preferable.

It is suitable that the particle size of the powder of the electrolyte and glucose component used as the raw materials used is 250 μm or less, preferably 180 μm or less, more preferably 100 μm or less. If the particle size exceeds 250 μm, the mechanical strength of the final granules becomes insufficient, and the granules become pulverized and deteriorate, and the dissolution rate becomes slow, which is not preferable.

The particle size of the granulated particles is preferably about 0.1 to 10 mm. If the particle size of the granules is less than the above range, the fluidity is impaired, or the particles become scattered and scattered, making it difficult to handle. Conversely, if the particle size exceeds the above range, the mechanical strength of the particles decreases. Both of them are not preferable because they may occur or the dissolution may take too long.

When drying the granulated product, it is desirable to carry out the drying under a lower temperature condition in order to prevent the progress of the yellowing of glucose due to the heating during the drying. Therefore,
It is preferable to use heated air after dehumidification. It is appropriate to carry out drying at 30 to 90 ° C. As a specific drying means, for example, a band dryer, a disk dryer, an aeration dryer, a rotary dryer, etc. can be used to obtain high strength and easy drying. It is possible to obtain granules that are soluble, uniform, and have a stable composition.

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.

When the present invention is applied to a sodium bicarbonate dialysis agent,
Baking soda component as alkalizing agent (hereinafter referred to as agent B)
Is not particularly limited, and may be supplied as a concentrated solution or powder. When it is supplied in the form of powder, it is preferable that the agent B is also granulated because the fluidity is improved and dust generation can be suppressed.

Part of the glucose of the agent A may be blended with the agent B. In this case, the agent B is a mixed granulation of baking soda and glucose. However, it is necessary to be careful because agent B containing glucose is prone to bacterial growth.

The present invention can also be applied to an acetic acid dialysis agent.
In this case, sodium acetate is further added to the agent A in the sodium bicarbonate dialysis agent to obtain a powder. Then, yellowing can be prevented by controlling the amount of water in the same manner as described above.

[0021]

【Example】

(Example 1) Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, sodium acetate anhydrous and glucose each crushed to an average particle size of about 50 μm were mixed in the following ratio, and further, On a dry basis
1.5 wt% water was added and mixed. NaCl 74.7110 wt% KCl 1.7943 〃 CaCl ₂・ 2H ₂ O 2.2839 〃 MgCl ₂・ 6H ₂ O 1.2408 〃 CH ₃ COONa 7.9296 〃 Glucose 12.0404 〃

The mixture was granulated using an extrusion granulator having a screen diameter of 0.5 mm to obtain 100 kg of cylindrical particles having a diameter of 0.5 mm and a length of 1 to 10 mm. Next, using air (room temperature) with a relative humidity of 70%, the particles were put into a batch-type box dryer whose temperature was adjusted to 50 ° C. for 3 hours while blowing air dehumidified to a relative humidity of 50% in advance. Dried. Thereafter, 1.5% by weight of glacial acetic acid was further added, and this was used as the agent A. This agent A was granular and had a pore volume of 0.08 cm ³ / g as measured by a mercury porosimetry porosimeter.

The water content of this agent A was measured by the Karl Fischer method of the Japanese Pharmacopoeia. Store after packaging,
It was subjected to a yellowing test. The packaging bag shall be an aluminum laminate bag of 30 cm x 40 cm, which completely prevents the permeation of moisture from the outside. After packaging, heat seal it, store it at room temperature for 1 year at room temperature, then open it, and visually and glucose in the Japanese Pharmacopoeia. The degree of yellowing was determined by measuring the absorbance by the method for measuring 5-hydroxymethylfurfural in the injection solution. Here, if the absorbance value is 0.1 or less, it is almost white and does not impair the commercial value at all, and if it is 0.2 or less, it is slightly yellow and there is no problem, and about 0.3 is considered to be the allowable limit. The results are shown in Table 1.

(Examples 2 to 4) The agent A crushed, mixed and granulated by the same procedure as in Example 1 was heated to the temperature.
Put in a batch type box dryer adjusted to 50 ° C, change the drying time as shown in Table 1 to adjust the water content in the agent A,
Thereafter, glacial acetic acid was further added in an amount of 1.5% by weight to give Examples 2 to 4.

(Example 5) Pulverized and mixed by the same operation as in Example 1 and granulated using an extrusion granulator having a screen diameter of 1.2 mm, and cylindrical particles having a diameter of 1.2 mm and a length of 1 to 10 mm. And was placed in a batch-type box dryer whose temperature was adjusted to 50 ° C. and dried for 3 hours. After that, 1.5% by weight of glacial acetic acid was further added, and this was made to be Example 5.

(Comparative Example) Crushing and mixing were carried out in the same manner as in Example 1 and granulated using an extrusion granulator having a screen diameter of 1.2 mm to obtain cylindrical particles having a diameter of 1.2 mm and a length of 1 to 10 mm. Then, under the same conditions, the air (room temperature) having a relative humidity of 70% was introduced into the dryer as it was without being dehumidified, and the mixture was placed in a batch type box dryer adjusted to 50 ° C. and dried for 3 hours. Thereafter, 1.5% by weight of glacial acetic acid was further added, and this was used as a comparative example.

[0027]

[Table 1]

[0028]

EFFECT OF THE INVENTION The dialysis agent of the present invention dissolves in water to form a homogeneous aqueous solution, and a dialysis solution can be easily obtained, and the yellowing of glucose can be prevented. Can be stored. In addition, this dialysis agent
The volume can be made small, and it is advantageous for storage or transportation because it does not powder when stored or does not form a sparingly soluble compound. Furthermore, since it has excellent fluidity, it is easy to handle.

Claims (2)

[Claims] 1. A dialysis agent in which a solid electrolyte and a glucose component are mixed, and the water content in the mixture is 2.0% by weight or less. 2. The dialysis agent according to claim 1, wherein baking soda is separately used as the alkalizing agent.