JPS5827246B2 - Method for producing electrolyte compound mixed powder for bicarbonate dialysis - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for producing an electrolyte compound mixed powder for bicarbonate dialysis, and more specifically, by simply dissolving it in water, it has specific electrolyte ions and an appropriate pH, During the preparation of the artificial perfusate, rapid pH fluctuations and precipitation of calcium and magnesium salts do not occur, and the chemical reactions in the perfusate proceed slowly, resulting in the original excellent artificial perfusate for bicarbonate dialysis. The present invention relates to a method for producing a new powdered electrolyte compound mixture that can always exhibit stable effects.

The artificial perfusion solution for bicarbonate dialysis, also called picarbonate dialysate, is one of the perfusion agents for artificial kidneys used in hemodialysis.

This is usually a combination of a solution containing various electrolyte compounds necessary for hemodialysis (Liquid A or main raw material) and an aqueous solution of bicarbonate (NaHCo3) as an alkaline agent (Liquid B or auxiliary raw material). During dialysis, the two are mixed and perfused into an artificial kidney device.

The above dialysate is physiologically appropriate, as sodium bicarbonate used as an alkaline agent is known to be a direct regulator of body fluid pH, and improves acid-base balance in metabolic acidosis, respiratory alkalosis, etc. It exhibits fast-acting properties that can efficiently and quickly perform dialysis, and there are fewer indeterminate complaints such as hypotension and nausea during dialysis, and rapid water removal is possible. It is highly expected to be effective and safe for correcting acetateemia, especially for large-area, short-time dialysis.

However, the sodium bicarbonate used as the alkaline agent (solution B) has low solubility and is unstable to pH and heat. This has the fatal disadvantage of generating gas, causing an increase in pH and a decrease in carbon dioxide pressure, which causes calcium and magnesium in Solution A to precipitate out as carbonates.

Therefore, conventionally, when preparing the above-mentioned picarbonate dialysate, in order to keep the pH of the dialysate neutral, a mixing tank (
A method of introducing carbon dioxide into the reaction tank to supplement the degassed carbon dioxide, or adding an appropriate amount of hydrochloric acid or acetic acid into the reaction tank or into the A liquid to adjust the pH and
This requires complicated operations such as a method of uniformly mixing the liquid as dilute a solution as possible, as well as highly accurate concentration and pH control.

In particular, the method of adjusting the pH in advance by adding an appropriate acid to Solution A is possible in terms of equipment and operation, but since Solution A itself is a liquid agent, there is a problem with storage stability. Even if the acid is uniformly added and mixed, it is difficult to avoid fluctuations in liquid properties over time due to storage, etc., and there is a risk that unforeseen dangers due to changes in quality may occur in practice.

Moreover, the above-mentioned solution A has a large volume and weight, making it extremely inconvenient to transport and handle.As mentioned above, picarbonate dialysate is highly effective in its dialysis effects, and is attracting attention. There are various problems that need to be resolved in practical terms, such as complexity in preparation, limitations on liquid properties such as concentration, temperature, and pH, and complexity in management, as well as inconvenience in storage, transportation, etc. There is.

The present inventor has discovered various advantages found in the above-mentioned picarbonate dialysate, namely, that the effect of improving metabolic azidosis occurs quickly and efficiently, and that it improves the effects of headache, vomiting, nausea, chest pain, palpitations, decreased blood pressure, convulsions, etc. Focusing on the fact that there are very few complaints,
Various studies have been conducted with the aim of developing techniques that will facilitate the preparation and management of the dialysate.

In the process, I came up with a new idea of powdering Solution A after adjusting the pH with the acid mentioned above, and actually spray-dried it. However, almost all of the acid components were scattered during drying, and the resulting powder was mixed with water again. Although the desired acidic pH can be maintained during dissolution, it has been recognized that in practical use, it is still necessary to add an acid to adjust the pH when mixing with liquid B as in the past.

In addition, when powders such as electrolyte compounds are intentionally made acidic,
Generally speaking, it is possible to attach acid directly to the surface of the above powder by following a method such as pickling, but if the above method is applied to commonly available electrolyte compound crystals or powder to attach the desired acid. It was recognized that the powder became wet and could maintain the desired powder state, but when it was dried, acid scattering still occurred and the purpose could not be achieved.

However, in subsequent research, the present inventor found that sodium chloride, which is the main component in the electrolyte compound, was made into an ultrafine powder of about 20 to 30 microns using a micronizer, and when glacial acetic acid was sprayed onto it, the desired pH could be adjusted. Addition of as much acetic acid as possible produces an aceticated sodium chloride powder with excellent powder flowability without the need for any drying, which can then be powder mixed with other electrolyte compounds required for hemodialysis. It has been found that the desired pH-adjusted solution A can be powdered by this method, and that this powder can be easily sealed and packaged, is easy to handle, and is extremely stable over time.

The present invention was completed based on this new knowledge.

That is, in the present invention, electrolyte compounds for preparing an artificial perfusion solution for bicarbonate dialysis are mixed in powder form, and NaCl, KCl, C
aCl2・2H20, MgCl2・6H20 and CH3
This is a method for obtaining an electrolyte compound mixed powder consisting of COONa or CH3COONa-3H20, in which chloride, which is the main component of the electrolyte compound, is used. The present invention relates to a method for producing an electrolyte compound mixed powder for bicarbonate dialysis, characterized by using sodium chloride powder made acidic by acetic acid by spraying 2 to 4% by weight of glacial acetic acid.

According to the method of the present invention, it is possible to produce an electrolyte compound mixed powder that is adjusted to a desired pH value and is extremely useful as solution A for bicarbonate dialysate by simply dissolving it in water.

Since the powder product is a powder, it can be easily stored and transported in sealed packaging, and the product does not suffer from any changes in quality, including pH changes, even during long-term storage. It does not substantially occur and always has a stable and constant quality.

Furthermore, most importantly, when the powder product obtained by the method of the present invention is dissolved in water and used as liquid A, even when mixed with liquid B, abnormal carbon dioxide generation, decrease in carbon dioxide pressure, No local pH increase occurs, and there is virtually no risk that calcium or magnesium will precipitate as carbonate.

Therefore, it is possible to very easily prepare a picarbonate dialysate that is always stable and exhibits appropriate pH1 electrolyte ion composition, carbonate ion concentration, carbon dioxide gas pressure, etc.

Of course, the picarbonate dialysate prepared from the powder product obtained by the method of the present invention has various excellent hemodialysis effects such as improvement of metabolic and dialysis and reduction of indefinite complaints without any adverse effects. , rather, it is more pronounced because the dialysate is easy to prepare and there is no variation in quality.

As described above, the present invention makes it possible to easily prepare a picarbonate dialysate that exhibits excellent hemodialysis effects, is easy to handle, and always has a stable quality.
The present invention provides a new electrolyte compound mixed powder product that has never been seen before, and its industrial value is enormous.

In the present invention, it is essential to use acetic acid acidic sodium chloride powder treated by a special method.

As the sodium chloride used as a raw material in this method, specifically, crystals or crystalline powder containing 199.5% or more of NaC as recorded in the Japanese Pharmacopoeia are used.

This normally has a size of about 500 to 600 μm door, and in the present invention, this size is about 20 μm using a micronizer.
Ultra-fine powder with a particle size of ~30 μm.

There are no particular restrictions on the micronizer used, but it is preferable to use a micronizer that can perform pulverization and classification at the same time and extract particles of the desired particle size. Preferably, the number is between 2000 and 3000 r, p, m.

The particle size of the sodium chloride prepared as described above has an important influence on whether the sodium chloride does not dry out and remains in powder form even after adding the required amount of glacial acetic acid during the subsequent spray addition of glacial acetic acid. It maintains a good powder state in the above range of about 20 to 30 μm.

Next, in the present invention, glacial acetic acid is added to the ultrafine sodium chloride by spraying.

This is specifically carried out in a suitable container, such as a rotating stirring tank.

As glacial acetic acid, CH3CO0H (6
0.05) Use one containing 99.0% or more or JIS, reagent special grade.

Specifically, the spray addition can be carried out using, for example, a pressure nozzle set in the center of a rotating stirring tank.

The amount of glacial acetic acid spray added ranges from 2 to 4% by weight of the weight of sodium chloride.

The sodium chloride acidified with acetic acid obtained by adding within this range maintains a powder state, and when the electrolyte compound mixed powder of the present invention obtained by using this is used as solution A for bicarbonate dialysate. The liquid can exhibit an ideal pH, ie around 45.

The reason why the thus obtained acetic acid-acidic sodium chloride powder has excellent powder fluidity is that countless ultrafine powder sodium chloride particles are adsorbed to the sprayed atomized glacial acetic acid, and the second grade ultrafine powder sodium chloride particle group is This is thought to be because the above powder is configured in the form of a cylinder of acetic acid.

In any case, the powder thus obtained is stable for a long period of time, has powder fluidity, and can be easily mixed with other electrolyte compounds without any drying.

In the method of the present invention, the acetic acid acidified sodium chloride powder produced above is mixed with other electrolyte compounds to obtain the desired electrolyte compound mixed powder for bicarbonate dialysate.

Other electrolyte compounds include common compounds used as raw materials for this type of dialysate, specifically potassium chloride (KCI), which is listed in the Japanese Pharmacopoeia, the Official Food Additives Standard, etc., and is also a JIS standard reagent. Calcium chloride (CaC12
・2H20), magnesium chloride (Mg C12・6H
20), sodium acetate (CH3COONa or CH3
COONa-3H20) etc. can be used.

The mixing of each of these electrolyte compounds is carried out in a conventional manner, and the mixing ratio is as follows: The ionic composition is determined as appropriate.

C11 H3COO CO3 35-140mEq/J O-4.0rrLEq/1 2, 5-3.5 mEq/1 1, O-1.5 mEq/1 06-107.5 mEq/1 4-9mEq/J 7, 5 to 35 mEq/J The dialysate having the above ionic composition preferably contains the following electrolyte compounds and NaHCO3 in a weight ratio.

aCI KCI CaCClCaCl2 -2H20・6H20 CH3COONa NaHCO3 59,474~62,6 1.157~1.99 0.978~2,73 0.676~1,63 1.455~6.59 24.763~30. 5 44% by weight 8 〃 8 〃 4 〃 5 〃 62 〃 By sealing the mixed powder of the present invention, it can be made into a product that has excellent storage stability over a long period of time and is extremely easy to handle. .

In addition, this product can be used as solution A for bicarbonate dialysate simply by dissolving it in an appropriate amount of water.
The thus obtained liquid A can be expected to have sufficient effects even without adding new acid or blowing carbon dioxide gas into the mixing tank when mixing with liquid B.

Examples and reference examples are given below to explain the present invention in more detail.

Example ■ 100 kg of sodium chloride as described in the Japanese Pharmacopoeia is crushed using a micronizer (impact type crusher, 8000 rpm) to obtain an ultra-fine powder of about 20 to 30 micron nails. Next, the ultra-fine powder of sodium chloride is mixed with glacial acetic acid (JIS). Special grade reagent, CH3CO0
Add H99, 5% or more) by spraying.

Acetic acid sodium chloride powder (CH
The following electrolyte compounds are mixed in powder form into 3COOH acidic NaC1).

CH3CO0H acidic NaCI KCI (Japanese Bureau) CaC12・2H20 (Japanese Bureau MgCl2・6H20 (Food Additive CH3CO0Na (Food Additive) 87.560% by weight 2.624 II ) 3.622 // ) 2.146 // 4.048 〃 Thus, the electrolyte compound mixture powder for bicarbonate dialysate of the present invention is obtained.

Reference Example 1 Powder (A) 2.4861 for each lot obtained in Example 1 was dissolved in 101 water and adjusted to pH 4.5.
Electrolyte solution for bicarbonate dialysis (liquid A) sample (lots) Al~
5) is obtained.

In addition, sodium bicarbonate powder (NaHC) described in the Japanese Pharmacopoeia
O2) Addressed to 882'fl, husband 201! Dissolve in water,
Obtain an aqueous sodium bicarbonate solution (solution B) with a pH of 8.1.

The above A and B solutions were respectively charged into the main stock solution tank and the sodium bicarbonate water tank of a multi-dialysate supply device (KH-20AB type manufactured by Nigro Co., Ltd.), and the total amount in the mixing tank was 35.
The electrolyte ion concentration (TrLEq/l) when the bicarbonate dialysate is diluted with warm water (35 to 40°C) and sent to the supply tank and console in order to obtain 0.07 is as shown in Table 1 below at the end console It was as shown in

For Na+ and K+ ions, use a flame photometer (I, L,
For HCO3 ions, a gas analyzer (1,L, meter, micro 13,
United States 1. (manufactured by Company L), and Ca2+, Mg2+, C
The concentrations of H3COO and CI ions were measured using the quantitative methods described in the Japanese Pharmacopoeia and the Food Additives Official Standards.

It can be seen from Table 1 above that when the powder obtained by the method of the present invention is used, the variation in electrolyte ions can be substantially ignored, and a dialysate of extremely constant quality can be supplied.

Note that even if 30 mEq/l is used as the B solution, the HCO3 ion concentration becomes 27 to 28 mEq/l in the dialysate because it partially reacts with acetic acid to form H2CO3.

In addition, the pH, PO2, Mi1℃02, and HCO3 of each dialysate (each of lots 1 to 5 were used as liquid A samples) in the mixing tank, supply tank, and console section.
The results of examining the ion concentration are shown in Table 2 below.

Each measurement was carried out using a gas analyzer (1.L. Meter Micro 13.1. manufactured by L Co., Ltd.).

From Table 2 above, it can be seen that the bicarbonate dialysate prepared using the powder of the present invention can be maintained at a pH of 7.35 or less, which is suitable for contacting the patient's blood through the dialysis membrane in the terminal console, and that the pH fluctuation It is extremely stable with almost no PCO2 (the neutralization reaction progresses slowly), and the HCO3 ion concentration remains constant at a value close to the theoretical value.
It can also be seen that a constant value of around 60rn7ILHg, which is appropriate for a dialysate, is maintained.

As described above, it is clear that according to the present invention, it is possible to easily provide a picarbonate dialysate that has constant quality and is always reproducible without substantial variation between lots.

Claims (1)

[Claims] 1. Each electrolyte compound for preparing an artificial perfusion solution for bicarbonate dialysis is mixed in powder form to produce NaCl, KCl, CaCl2,
2H20, MgCl2・6H20 and CH3COONa
Alternatively, there is a method for obtaining an electrolyte compound mixed powder consisting of CH3COONa-3H20, in which IJium (chloride, which is the main component of the electrolyte compound) is made into an ultrafine powder of about 20 to 30 microns using a micronizer, and then glacial acetic acid is added to this. A method for producing an electrolyte compound mixed powder for bicarbonate dialysis, characterized in that ultrafine powder of sodium chloride is made acidic by acetic acid by spraying 2 to 4% by weight of sodium chloride. 2 The electrolyte compound mixed powder contains 83.263 to 88.887% by weight of sodium chloride acidified with acetic acid, 0 to 4.415% by weight of KCI, and 2.7% of CaCl2.2H20.
20-3.875% by weight of MgCl2.6H20 at 1.
505 to 2.296% by weight and 4.048 to 8.767% by weight as CH3COONa.