JP2003104869A - Agent for dialysis and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a physiological agent for dialysis, containing an electrolytic component, a pH conditioner and/or glucose for preparing an artificial pericardial fluid for bicarbonate dialysis, stable as a preparation, and free from acetic acid. SOLUTION: This agent for the dialysis contains citric acid and sodium citrate, and has a pH regulated so as to be 2.2-2.9.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a dialysis agent and a method for producing the same.

[0002]

2. Description of the Related Art Hemodialysis (artificial dialysis) is one of the most common blood purification therapies for patients with chronic renal failure. The hemodialysis treatment method aims to improve serum electrolyte concentration, correct acid-base balance, etc. in addition to removing waste products and removing water. The dialysate used for this requires a large amount of alkalizing agent, which is removed by dialysis due to the small molecule of bicarbonate ion, which is an alkalizing agent in the living body. Low HC
O ₃ ^- in order to prevent that lead to hyperlipidemia. Therefore, it is natural that bicarbonate is the most suitable alkalizing agent, but in bicarbonate dialysate, bicarbonate ion reacts with calcium ion and magnesium ion to form an insoluble compound (metal carbonate such as calcium carbonate or magnesium carbonate). However, there is a problem in that it is difficult to store for a long period of time because it produces salt and is unstable, and because bacteria are easily proliferated.

Therefore, a method for replenishing alkali has been established by utilizing the fact that acetic acid is metabolized in the liver and converted into bicarbonate, and a stable dialysate can be supplied. Therefore, acetic acid using an acetate salt as an alkalizing agent. Dialysis started. As a result, it became possible to set a high alkali concentration, and it became possible to replenish the bicarbonate sufficiently.
Acetic acid has vasodilatory and cardiac function suppressing effects, and in the case of acetic acid intolerance with slow acetic acid metabolism, the exacerbation of dialysis imbalance syndrome caused by acetic acid and a large amount of CO ₂ in the blood during dialysis are dialyzed. Lost inside, the problems such as respiratory depression appeared.

[0004] Thereafter, as the number of dialysis patients increases and the number of patients with diabetes mellitus and the like expands, the frequency and severity of dialysis imbalance syndrome increase, and asymptomatic dialysis is performed in which even normal dialysis patients have minimal discomfort during dialysis. Demand has increased, and because the involvement of acetic acid was strongly suspected as the cause of these symptoms,
At present, the mainstream is acetic acid dialysis which uses acetate as an alkalizing agent, and bicarbonate dialysis which uses sodium hydrogen carbonate.

[0005]

[Problems to be Solved by the Invention] In this bicarbonate dialysis,
Generally, it has a two-agent structure of "A agent" containing an electrolyte component containing calcium ions and magnesium ions, etc., a pH adjuster and / or glucose, and "B agent" consisting of sodium bicarbonate of bicarbonate ion. There is. this is,
This is because the bicarbonate ion reacts with calcium ion and magnesium ion to produce a metal carbonate which is an insoluble compound. However, even though it is bicarbonate dialysis, the pH
It contains 8-12 mEq / L of acetic acid, such as acetic acid and sodium acetate as regulators, although not as much as the previous acetic acid dialysis. Initially, it was thought that the addition of acetic acid in this amount was not a problem, but since acetic acid originally does not exist in the living body (0.1 mEq / L or less), recently, due to prolonged dialysis, The development of clinical symptoms such as headache during dialysis and lowering of blood pressure, which is thought to be caused by acetic acid, has become a problem. Also, due to improvements in the performance of the dialyzer, acetic acid is overloaded and adversely affects the circulatory system, and it is recognized that the toxic effect of acetic acid, such as acetic acid intolerance, is stronger than expected. It's coming. Therefore, there is a demand for the development of a dialysis preparation that does not contain acetic acid.

[0006]

Means for Solving the Problems The present invention has been completed as a result of extensive studies to solve such problems, and it has been completed. An artificial perfusate for bicarbonate dialysis used for hemodialysis is prepared. The present invention provides a dialysis agent containing an electrolyte component, a pH adjuster and / or glucose, which does not contain acetic acid and acetate.

That is, the present invention is as follows: A dialysis agent containing an electrolyte component, a pH adjusting agent and / or glucose for preparing an artificial perfusate for bicarbonate dialysis, which contains citric acid and sodium citrate and is adjusted to pH 2.2 to 2.9. 2. A dialysis agent characterized by the following: A dialysis agent containing an electrolyte component, a pH adjuster and / or glucose for preparing an artificial perfusate for bicarbonate dialysis, which contains citric acid and sodium citrate, and the mixing ratio of citric acid and sodium citrate is adjusted. 2. The dialysis agent according to claim 1, wherein the pH is adjusted to 2.2 to 2.9 by changing the pH. pH is adjusted to 2.3-2.7, The dialysis agent of Claims 1-2 characterized by the above-mentioned. 4. A dialysis agent, which is prepared as an artificial perfusion solution for bicarbonate dialysis by diluting and mixing the dialysis agent according to any one of claims 1 to 3 with an aqueous solution of sodium hydrogen carbonate. A dialysis agent containing an electrolyte component, a pH adjusting agent and / or glucose for preparing an artificial perfusate for bicarbonate dialysis, which contains citric acid and sodium citrate and is adjusted to pH 2.2 to 2.9. A method for producing a dialysis agent, which is characterized by the above.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, a dialysis agent containing an electrolyte component, a pH adjusting agent and / or glucose for preparing an artificial perfusate for bicarbonate dialysis is used as a substitute for acetic acid and acetate. It is characterized by using citric acid and sodium citrate, which are acids that are also present in the body. As a result, an acetic acid-free artificial perfusion solution for bicarbonate dialysis can be obtained.

The dialysis agent in the present invention is a concentrated solution for preparing an artificial perfusion solution for bicarbonate dialysis by diluting and mixing with a sodium hydrogen carbonate solution.

This dialysis agent contains an electrolyte component, a pH adjuster and / or glucose. As the electrolyte component, in addition to citrates such as sodium citrate, for example, sodium chloride, potassium chloride, magnesium chloride, Calcium chloride, sodium lactate, potassium lactate,
Calcium lactate or the like is used. Preferred electrolyte compositions are sodium chloride, potassium chloride, magnesium chloride, sodium citrate.

The amount of each component of the dialysate, when diluted and mixed to an appropriate concentration, gives an artificial perfusate for bicarbonate dialysis.
The following concentrations are preferred. Na ⁺ 120 to 150 mEq / L K ⁺ 0 to 4 mEq / L Ca ⁺⁺ 0 to 4 mEq / L Mg ⁺⁺ 0 to 1.5 mEq / L Cl ⁻ 55 to 135 mEq / L HCO ₃ ⁻ 20 to 45 mEq / L citric acid 0.02-5 mEq / L glucose 0-3.0 g / L

In the present invention, the pH adjusting agent is
In addition to citric acid, lactic acid, hydrochloric acid, malic acid, ascorbic acid, tartaric acid, sodium hydroxide and the like can be used.

When citric acid and sodium citrate are used, calcium ions contained as an electrolyte component and an insoluble compound are produced, and the pH is adjusted to 2.9 or less, more preferably pH 2.7 or less by citric acid. This can prevent the formation of insoluble compounds.

Further, by adjusting the pH with citric acid to 2.2 or more, more preferably pH 2.3 or more,
It is possible to prevent the decomposition of glucose.

Further, by using citric acid,
A precipitation suppression effect can also be expected. Two agents, a so-called "A agent" containing an electrolyte component, a pH adjuster and / or glucose, and a "B agent" consisting of sodium bicarbonate of bicarbonate ion, are produced by reacting bicarbonate ion with calcium ion and magnesium ion. In order to produce a metal carbonate, which is an insoluble compound, it is diluted and mixed at the time of use to obtain an artificial perfusion solution. At this time, there is also an advantage that stability is maintained for a long time due to the effect of suppressing the precipitation of citric acid.

In the present invention, the amount of citric acid used is pH 2.
It may be adjusted to 2 to 2.9, and usually citric acid is about 0.02 to 5 mEq / L, more preferably 0.5 to 3 m.
Eq / L.

In the conventional so-called "A agent", an acetate salt was contained, whereas in the present invention, acetic acid was not contained at all and only sodium hydrogencarbonate was used as an alkalizing agent. There is also an advantage that

[0018]

EXAMPLES Next, the present invention will be described in more detail with reference to examples.

Example 1 The following four formulations having different pH are prepared for dialysis agents containing an electrolyte component, a pH adjusting agent and glucose for preparing an artificial perfusate for bicarbonate dialysis. That is, sodium chloride (NaCl) 214.
8 g, potassium chloride (KCl) 5.22 g, calcium chloride (CaCl ₂ .2H ₂ O) 7.72 g, magnesium chloride (MgCl ₂ .6H ₂ O) 3.56 g, glucose 52.5 g and citric acid as a pH adjuster (C ₆ H ₈
O ₇ ) 5.38 g was dissolved in water to make 1 L and formulated (pH 1.6). The pH adjuster of this formulation was 4.48 g of citric acid and sodium citrate (C ₆ H ₅ Na _3).
O ₇ ) changed to 1.20 g and formulated (p
H2.2), citric acid 3.36 g and sodium citrate 2.71 g were prepared by changing the formulation (pH
2.9), prepared by changing to 2.02 g of citric acid and 4.52 g of sodium citrate and prescribing (pH
3.6).

For these liquids, 40 ° C./75% RH
Stored under the following conditions, the properties and degradation products of glucose 5-
Changes in hydroxymethylfurfural (5-HMF) and levulinic acid were observed. The properties are visually observed, and 5-HMF and levulinic acid each contain 10 mL of each formulation.
Accurately, and about 11 mL of water added accurately,
An ultraviolet / visible spectrophotometer (UV-2200 type manufactured by Shimadzu Corporation) is used to measure the absorbance at a wavelength of 284 nm (5-HMF) and a wavelength of 263 nm (levulinic acid).

[0021]

[Table 1]

First, in terms of properties, as shown in Table 1, p
In the formulation with the highest H, a white precipitate was observed after storage for 1 week, but in the other formulations, no change was observed even after storage for 4 weeks.

[0023]

[Table 2]

Table 2 shows the results of 5-HMF and levulinic acid, which are decomposition products of glucose. The production amount of 5-HMF and levulinic acid was higher in the formulation having the lowest pH. From these results, it is judged that the formulation in which the pH is adjusted to 2.2 and the formulation in which the pH is adjusted to 2.9 with citric acid and sodium citrate are pharmaceutically stable.

Example 2 First, sodium chloride (Na
Cl) 214.8 g, potassium chloride (KCl) 5.22
g, calcium chloride (CaCl ₂ .2H ₂ O) 7.72
g, magnesium chloride _{(MgCl 2 · 6H 2 O)} 3.5
6 g, glucose 52.5 g, citric acid (C ₆ H ₈ O ₇ ) 4.03 g and sodium citrate (C ₆ H ₅ Na ₃ O ₇ ) 1.81 g as a pH adjusting agent were dissolved in water to give 1 L.
And prescription (pH 2.4). Next, 29.4 g of sodium hydrogen carbonate is dissolved in water to make 1 L. Water is added to 35 mL of this aqueous solution to make about 300 mL, 10 mL of the formulation is added thereto, and water is added to make 350 mL to prepare an acetic acid-free artificial perfusion solution for bicarbonate dialysis according to the formulation. Also, 214.8 g of sodium chloride (NaCl),
5.22 g of potassium chloride (KCl), 7.72 g of calcium chloride (CaCl ₂ .2H ₂ O), 3.56 g of magnesium chloride (MgCl ₂ .6H ₂ O), 28.7 g of sodium acetate (C ₂ H ₃ NaO ₂ ). , 35 g of glucose and an appropriate amount of hydrochloric acid (HCl) as a pH adjuster are dissolved in water to make 1 L, and a formulation (pH 4.9) is obtained. Next, 21.0 g of sodium hydrogen carbonate is dissolved in water to make 1 L. Water is added to 35 mL of this solution to make about 300 mL, 10 mL of the formulation is added thereto, and water is added to make 350 mL to prepare an artificial perfusion solution for bicarbonate dialysis according to the formulation. These are stored at room temperature and the properties are observed.

[0026]

[Table 3]

The results are shown in Table 3. In the artificial perfusate for bicarbonate dialysis according to the prescription, a precipitate was formed after 3 days, whereas in the artificial perfusate for bicarbonate dialysis according to the prescription, no precipitate was formed even after 5 days. From this, it is judged that the acetic acid-free artificial perfusate for bicarbonate dialysis is stable.

[0028]

INDUSTRIAL APPLICABILITY As described above, according to the present invention, an electrolyte component and pH for preparing an artificial perfusate for bicarbonate dialysis are used.
A dialysis agent containing a regulator and / or glucose, containing citric acid and sodium citrate,
By adjusting to 2.2 to 2.9, a physiologically dialysis agent that is stable in terms of formulation and is acetic acid-free can be provided.

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Claims (5)

[Claims] 1. A dialysis agent containing an electrolyte component, a pH adjuster and / or glucose for preparing an artificial perfusate for bicarbonate dialysis, which contains citric acid and sodium citrate and has a pH of 2.2-2. A dialysis agent characterized by being adjusted to 0.9. 2. A dialysis agent containing an electrolyte component, a pH adjuster and / or glucose for preparing an artificial perfusate for bicarbonate dialysis, which comprises citric acid and sodium citrate, and citric acid and citric acid. The dialysis agent according to claim 1, wherein the pH is adjusted to 2.2 to 2.9 by changing the blending ratio of sodium. 3. The dialysis agent according to claim 1, wherein the pH is adjusted to 2.3 to 2.7. 4. By diluting and mixing the dialysis agent according to any one of claims 1 to 3 with an aqueous solution of sodium hydrogen carbonate,
A dialysis agent prepared as an artificial perfusion solution for bicarbonate dialysis. 5. A dialysis agent containing an electrolyte component, a pH adjusting agent and / or glucose for preparing an artificial perfusate for bicarbonate dialysis, which contains citric acid and sodium citrate and has a pH of 2.2-2. The manufacturing method of the dialysis agent characterized by adjusting to 9.