KR101779676B1 - Methods for manufacturing dialysate chemical formulations - Google Patents

Abstract

The present invention relates to a method for preparing a composition for preparing a dialysis liquid containing sodium chloride, calcium chloride, potassium chloride and magnesium chloride. The preparation of the present invention is characterized in that it does not include a pulverization step by freeze-drying to improve the uniformity of mixing, thereby shortening the manufacturing time and reducing the manufacturing cost.

Description

METHODS FOR MANUFACTURING DIALYSATE CHEMICAL FORMULATIONS BACKGROUND OF THE INVENTION 1. Field of the Invention [0001]

The present invention relates to pharmaceutical preparations for medicines used for dialysis, and more specifically, to pharmaceutical preparations for preparing a dialysis liquid having a uniform mixing degree and capable of reducing the manufacturing cost from existing ones in various aspects.

The use of dialysis solutions is essential for dialysis, and most dialysis solutions are currently divided into liquid and powder. The dialysis fluid preparation is prepared by the manufacturer, packed in a small container in a container, opened and applied to an artificial dialyzer. Immediately prior to use by the patient, the powder is added to the preparation tank for preparing the dialysis liquid, mixed with purified water and dissolved, and then applied to the artificial dialyzer. The disadvantage of the dialysis solution is that it is difficult to store or use because it is bulky and heavy, and that many logistics costs are used for transportation from the manufacturer to the manufacturer. In addition, the dialysis solution may be precipitated at a low temperature or may be denatured at a high temperature since it is dissolved at a high concentration. To compensate for these drawbacks, acid powders for the preparation of dialysate have been developed, and since the purified water is injected and dissolved during use, there is no cost for the production of pharmaceuticals, the weight and volume of purified water during delivery and storage.

In the case of powder for preparing dialysate, each raw material is separately packed in a packing unit, and all raw materials are packed in one packing unit. When the raw materials are separately packaged separately, the manufacturing cost has increased and it has been difficult to use about 5 to 7 packages in hospitals using the products. In order to improve the uniformity of the raw materials, all the raw materials are dissolved in purified water, and the raw materials are lyophilized and pulverized. This method has a disadvantage that it has to have a freeze dryer that it does not generally hold, and it is difficult to use because it is expensive because of the manufacturing time and the unit price, and the unit price of the product is increased, which is a burden to the patient. Korean Patent Laid-Open Publication No. 10-2010-0028586 discloses a method for inhibiting the decomposition of glucose by using a solid organic acid, but there is no content that can improve the mixing uniformity.

Korean Patent Publication No. 10-2010-0028586

The dialysis liquid agent is bulky and difficult to be transported. In the case of the acid agent for preparing a dialysis liquid, which is improved, there is a problem that it is inconvenient when the subdivided liquid is packed for each ingredient. In addition, when all the raw materials are mixed and packed, it is difficult to commercialize them because of high manufacturing cost in order to improve the uniformity of the mixture.

SUMMARY OF THE INVENTION Accordingly, the present invention has been made in view of the above problems, and it is an object of the present invention to provide a method for preparing a dialysis solution composition capable of reducing the production cost by overcoming the disadvantages of conventional dialysis liquid preparations.

In order to accomplish the above object, the present invention provides a method for producing a dialysis solution, which comprises packing raw materials for dialysis such as potassium chloride, magnesium chloride, potassium chloride, sodium chloride, and glucose in one packing unit, pulverizing the mixed raw materials so that the particle size D50 is 300 to 400 μm Thereby improving the mixing uniformity.

The homogeneity of the composition for preparing a dialysis liquid prepared by the manufacturing method according to the embodiments of the present invention is improved.

The manufacturing method according to the embodiments of the present invention does not include the step of lyophilizing and pulverizing to improve the homogeneity so that the manufacturing time is shortened and the manufacturing cost is reduced.

The effects and features of the present invention will become more apparent with reference to the following embodiments. However, the embodiments of the present invention are intended to be illustrative, but not limitative of the scope of the present invention, and are not intended to limit the scope of the invention to those skilled in the art. And the terminology used herein is for the purpose of illustrating embodiments and is not intended to limit the present invention.

In the case of the composition for preparing a dialysis solution, it is difficult to maintain the uniformity of mixing because the difference in the content of the main components is large. Due to these problems, it is not convenient to use in case of using sub-division for each ingredient. In case of mixing all of them, freeze-drying and pulverization are used. However, it takes a long time and the manufacturing cost is high. A manufacturing method that is not necessary is required.

The inventors of the present invention have studied various things to improve the mixing uniformity of the composition for preparing a dialysis solution in a commercially available manufacturing process. As a result, when sodium chloride, calcium chloride, potassium chloride and magnesium chloride of the composition for preparing a dialysis solution are mixed, To 400 [mu] m, the mixing uniformity is greatly improved. The present invention has been completed based on such high-level findings.

In the present invention, a mixture of at least one selected from the group consisting of sodium chloride, calcium chloride, potassium chloride and magnesium chloride is pulverized and sieved to a mesh size of 3030, and the D50 is adjusted to 300 to 400 μm. The mixture of sodium chloride, calcium chloride, potassium chloride and magnesium chloride may be further mixed with at least one selected from the group consisting of citric acid hydrate and glucose.

[Example]

< Example  1 > Preparation of composition for preparing dialysate

22,500 g of sodium chloride, 644 g of calcium chloride hydrate, 522 g of potassium chloride, 356 g of magnesium chloride hydrate, and 490 g of citric acid hydrate are mixed, pulverized and sieved to 30 mesh size.

&Lt; Comparative Example 1 > Preparation of composition for preparing dialysate

22,500 g of sodium chloride, 644 g of calcium chloride hydrate, 522 g of potassium chloride, 356 g of magnesium chloride hydrate, and 490 g of citric acid hydrate are mixed, pulverized and sieved to a mesh size of 40 mesh.

&Lt; Comparative Example 2 > Preparation of composition for preparing dialysate

22,500 g of sodium chloride, 644 g of calcium chloride hydrate, 522 g of potassium chloride, 356 g of magnesium chloride hydrate and 490 g of citric acid hydrate are mixed.

&Lt; Comparative Example 3 > Preparation of composition for preparing dialysate

22,500 g of sodium chloride, 644 g of calcium chloride hydrate, 522 g of potassium chloride, 356 g of magnesium chloride hydrate, and 490 g of citric acid hydrate are mixed, followed by pulverization and sieved to 25 mesh size.

<Experimental Example 1> Particle size measurement

The particle size D50 of the final mixed mixture of Example 1 and Comparative Examples 1 to 3 was measured.

Particle Size Analyzer: Particle Size Analyzer CILAS 1064

Particle size Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 d ₅₀ 347 μm 210 μm 638 μm 232 μm

<Experimental Example 2> Measurement of content distribution

Samples were taken at three points of each of the upper, middle, and lower portions of the final mixture prepared in the above Examples and Comparative Examples, and the ratio of the analyzed samples to the dose of each component was calculated and shown in Table 2 .

Raw material Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Sodium chloride 99.7 ± 1.5% 99.3 ± 1.1% 99.5 + 1.2% 99.3 ± 1.8% Calcium chloride hydrate 98.8 ± 2.2% 98.5 ± 3.8% 85.7 ± 8.4% 93.4 ± 5.5% Potassium chloride 97.4 ± 2.8% 98.6 ± 3.5% 93.4 ± 6.2% 95.5 ± 6.1% Magnesium chloride hydrate 97.9 ± 1.7% 97.5 ± 3.3% 90.4 ± 7.9% 92.7 ± 5.3% Citric acid hydrate 98.3 ± 2.1% 98.7 ± 2.8% 92.7 ± 6.5% 97.5 ± 4.0%

As a result, it was confirmed that Comparative Example 2, which was not pulverized, and Comparative Example 3, which pulverized to a size of 25 mesh, were not uniform in content. In the case of Example 1, the contents of all the main components were uniformly distributed. In the case of Comparative Example 1, the content was uniformly distributed, but the particle size was small and there was a problem in fluidity. If the particle size is small and the fluidity is high, it is difficult to pack the sub-division, which makes it difficult to use in actual products.

<Experimental Example 3> Measurement of osmotic pressure

Samples were collected (245.12 g) at the three points of the upper, middle, and lower portions of the final mixture prepared in the above Examples and Comparative Examples, and dissolved in 1 L of purified water to prepare an acid solution for dialysis. 88.2 g of sodium hydrogencarbonate is dissolved in 1.26 L of purified water to prepare a basic solution for dialysis. (Acidic solution for dialysis: basic solution for dialysis: purified water) is homogeneously mixed at a ratio of 1: 1.26: 32.74 and the osmotic pressure is measured with an osmotic pressure measuring device.

Osmometers: KNAUER K-7000 Vapor Pressure Osmometer

Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Osmotic pressure 305 ± 5.2 mosm / L 301 ± 15.7 mosm / L 280 ± 25.3 mosm / L 294 ± 17.2 mosm / L

The dialysis agent should have an osmotic pressure similar to the osmotic pressure of the blood (about 300 mosm / L) so that the dialysis normally occurs and there is no side effect to the patient. The factors that influence the osmotic pressure in the dialysis agent are the concentration of the ions, and if there is irregularity, the osmotic pressure may not appear uniformly, which may be a problem.

Experimental results showed that Example 1 maintained an appropriate osmotic pressure for hemodialysis applications and Comparative Examples 1 to 3 were not suitable for hemodialysis because of severe deviations.

Claims (2)

Sodium chloride; Calcium chloride or calcium chloride hydrate; Magnesium chloride or magnesium chloride hydrate; And potassium chloride is pulverized to have a D50 of 300 to 400 占 퐉. The method of claim 1, wherein the sodium chloride; Calcium chloride or calcium chloride hydrate; Magnesium chloride or magnesium chloride hydrate; And potassium chloride is further added to and mixed with at least one member selected from the group consisting of citric acid hydrate and glucose.