DD247842A1 - METHOD FOR PRODUCING A BICARBONATE-CONTAINING ELECTROLYTE AGENT - Google Patents

Abstract

The process provides a stabilized electrolyte agent for easy preparation of bicarbonate electrolyte solution for hemodialysis, which is a good storage-stable powder. The aim of the invention is to provide a means for easy preparation of bicarbonate electrolyte solution without any special effort. The invention has the object of stabilizing the agent in a simple process while avoiding particular expense in itself and to produce stable storage. For this purpose, the alkaline earth metal component in the form of carbonates are used, for the recipe ingredients used special Siebfeinheiten and executed the mixing grain gentle while maintaining special homogeneity. If necessary, special organic acids are used to achieve a special product quality. The preferred field of application is the preparation of agents for the preparation of hemodialysis or for diabetic purposes.

Description

Field of application of the invention

The method enables the simple production of a storage-stable agent for the preparation of so-called bicarbonate dialysis solution by a simple dissolution process, at the same time the calibration of the components is directly guaranteed to each other.

Characteristic of the known technical solutions

On a large scale, the treatment of renal insufficiency is performed today by so-called hemodialysis technique.

The electrolyte solution required in the dialysis process is prepared from electrolyte concentrate by suitable dilution and contains the medically important ions Na ⁺ , K ⁺ , Mg ²⁺ , Ca ²⁺ , Cl "and a considerable proportion of acetate ions Harmful, see the publication of E.Lenhardt, H. Thieler and H. Trenkmann, Pharmazeut Practice 38 (1983) H. 6, p 256. As will be further explained there, the use of bicarbonate-containing dialysis solution is much more advantageous for the patients.

Since Natriumhydrogenkarbonathaltige solutions are unstable and continue to come from the alkaline earth ions as carbonates to precipitate, no liquid concentrates in terms of currently industrially produced acetate-containing electrolyte concentrates can be applied. As a consequence, a bicarbonate dialysis solution must be prepared from the individual components and calibrated in an economically completely unsatisfactory apothecary technique.

There is therefore an urgent need to have a solid electrolyte mixture which leads to the calibrated dialysis solution by a simple dissolving process and contains no acetate ions. Immediately obvious to the skilled man, is by simple mixing of the formulation according mineral salts (NaCl, CaCl ₂ · 6H ₂ O; MgCl ₂ · 6H ₂ O; NaHCO ₃₎ expenses side (product manufacturing to packaging), such as quality-sided (accurate calibration, chemical and physical Storage stability), no acceptable result achievable. ,

Numerous proposals for the production of storage-stable mixtures with mineral constituents, eg. B. from the fertilizer industry, completely eliminated, because in the sense of this task improper ballast or toxins are introduced.

The methods proposed in US Pat. No. 3,560,380 and EP 0034916 for the preparation of an agent for the preparation of dialysis solutions include, inter alia. Also, because always sodium acetate, which is just to be avoided harmful fiber, a particularly important component of the mixture.

Object of the invention

The object of the invention is to produce the bicarbonate-containing electrolyte agent with a simple outlay, to calibrate the active substance side and to achieve good storage or quality stability. The agent should contain a minimum amount of fiber, it must be completely harmless, and allow the preparation of the user bicarbonate dialysis solution in a calibrated form by a simple solvent release of the agent.

Essence of the invention

The invention has as its object to provide a method according to which the electrolyte mixture (agent) by a technologically simple process powdery-free-flowing and storage-like quality stable produced. The agent should be readily soluble in water, thereby yielding a drug-side ready-calibrated, bicarbonate-containing electrolyte solution while avoiding substantial levels of spurious or bachelor's matter.

According to the invention the object is achieved by the method described below.

Only solid components are used.

The mixing of the components takes place in a mechanical mixing device of ordinary design with good Mischeffezienz. In contrast to the customary in such tasks grinding composition in the homogenization process, however, the equipment and operation is to be chosen so that the mixing process is gentle on the grain. In accordance with the invention, grain preserving mixing means obtaining the grain size (sieving fineness) of certain

Mixing ingredients with more than 75%, based on the grain of the initial state, characteristic of the finished product.

In suitable mixers, such a procedure, for. B. achieved by the rotational speed of the mixed material, the proportionate filling volume and the rotational speed of rotating mixing elements.

For the main component sodium chloride, a sieve fineness at 160 / xm ... 500> m is used at S 48%.

In this quality, a mol of sodium chloride with (0.5 ... 1.8) · a · 1 (T ² nnol basic magnesium compound, Siebfeinheit of less than 315 / ^ m to s 95% and (0.5 ... , 1) a 10 ~ ² mol calcium carbonate, sieve fineness smaller than 100 μm to § 90%, homogenized to a test mass homogeneity of (1 ... 7) g.

It is part of the essence of the invention to determine and limit the homogeneity of the mixture through a sample mass range. Sample mass is the number of grams to understand, which is always found with known analysis methods that the recipe components are in the desired ratio to each other (trial mass homogeneity).

Now b mol sodium bicarbonate, which is optionally replaced up to ^b / iomol by calibrating Natriumkarbonatgemisch, optionally with other formulation components, to a Probemassehomogenität of (5 ... 15) g so finely homogenized that a Restsiebfeinheit of better 75% of the starting materials is maintained ,

A high product quality places high demands on the tolerances, which are permissible with regard to the components (active substances) to each other. Furthermore, there is a need for the desired electrolyte solution to be achieved with always the same mass use of the agent (eg g / l), although variable content ranges are permitted for the commercial raw materials according to the quality regulation.

It is the essence of the invention to replace the required calibration simply by exchanging up to Vs of the sodium bicarbonate with a sodium carbonate mixture which is less crystalline than the so-called soda ash (Na ₂ CO 3 .10H ₂ O) to a necessary extent, preferably a sodium carbonate of less than 30 % Water of crystallization, also in the form of soda ash in a mixture with water containing soda.

The inventive composition is optionally adjusted in its ratio of sodium chloride to sodium bicarbonate or sodium carbonate so that the solution process to the dialysis solution with the addition of z. As hydrochloric acid, the important ions, including the originally bound as carbonate form in the desired medically advantageous final concentration with simultaneous formation of the stabilizing content of dissolved carbon dioxide can be ensured.

With the composition according to the invention it is possible to completely avoid the medically disadvantageous content of acetate ions, with known electrolyte agents to 20 ... 25mmol / l acetate content in the user solution, without causing an acetate content in z.Z. medically tolerated height of about 3mmol / l as a formulation component excluded in principle

The process is preferably carried out continuously. It also corresponds to the purpose of the process of working in stages with several particularly suitable mixing units.

According to the invention, the process can be embodied in a completely novel manner by adding a solid organic acid whose acidity is sufficient for displacing the carbonic acid from its compounds in the process step of the ready-homogenization. Another typical feature of such an organic acid is that its metabolism, weakened, causes the known disadvantages of acetate in the organism, preferably an organic dicarboxylic acid of pKs = 5, e.g. As adipic acid, aspartic acid or glutamic acid, for use or mixtures of them. The proportion of these acids is 1 to 10% higher in the mixture than results from a known equivalent chemical calculation (solution of alkaline earth carbonates; formation of dissolved carbon dioxide). The agent thus prepared results in a known manner in a simple dissolution process, the dialysis solution desired concentration without further acid additives. In this embodiment of the invention is also the addition of fiber, z. As acetic acid, completely avoided.

example

Without limiting the invention, the process is illustrated by the continuous production of one of many possible formulations for electrolyte agents according to the invention. For mixing, a commercially available mechanical mixer with cutting star, which was adjusted in its operation to 93% Kornerhalt applied. Special protective measures against humidity etc. are not required.

57.30 kg of sodium chloride, sieve fineness 160/500 μm to 65.2% are homogenized with 0.460 kg basic magnesium carbonate, sieve fineness 315 / xm to 99.9%, and calcium carbonate, sieve fineness smaller 100 / um by 94%, to a test mass homogeneity of 3.2 g ,

Now 1.51 kg of potassium chloride, 160/500 / s of sieve to 68%, 4.35 kg of sodium carbonate (water of crystallinity 23.8%) and 27.2 kg of sodium bicarbonate are added.

It is finally homogenized to a test mass homogeneity of 8.3 g with a residual sifting rate of 88.5%.

Net yield 90,6kg, white free-flowing powder.

15 packaging units of 5 kg (PE bags unsealed, cardboard drum) were stored normally without special air humidity protection. After one year, the electrolyte was unchanged as a loose, free-flowing powder.

To prepare the electrolyte solution for hemodialysis, 9.25 kg of test product was added to 90 ml of reverse osmosis water with vigorous stirring. To the milky-white mixture was added 97 ml of 1 M hydrochloric acid diluted to 10.01 with continued stirring, with continued stirring. The now clear colorless solution showed the following ion contents in mmol / l: K ⁺ 2.0; Ca ²⁺ 1.77; Mg ²⁺ 0.99; Na ⁺ 134.6; Chloride ions 106.

After customary prefiltration and fine filtration, the solution prepared from the electrolyte agent can be supplied to the hemodialysis device without further calibration.

The versatility of the method is to be emphasized by the sufficient for the expert note that means for the preparation of dietary electrolyte solutions for so-called intestinal diseases can be made advantageous. · *

Claims (3)

j Claims: 1. A process for the preparation of a bicarbonate-containing electrolyte, characterized in that only solid components are used, the mixing of which takes place in a mechanical mixing means granular, wherein first a mol of sodium chloride of Siebfeinheit 160μ.ΓΤΐ ... 500μιη to § 48% with (0, 5-1.8) · a · 10 " ² mol basic magnesium compound, sieving fineness of less than 315 / um to S 95% and calcium carbonate, sieving fineness less than 100, to S 90%, with (0.5 ... 3 , 1) · a · 10 ~ ² mol portion is homogenized to a Probemassehomogenität of (1 ... 7) g, now b mol sodium bicarbonate, which is optionally up to tysmol replaced by calibrating sodium carbonate, together with optionally further formulation components, and to the final product is homogenised to a test mass homogeneity of (5 ... 15) g and residual sifting fineness of better than 75%. 2. A process for the preparation of a bicarbonate-containing electrolyte agent according to item 1, characterized in that the electrolyte agent according to item 1 with a solid organic acid with pKs Si 5 in the amount of 1 ... 10% on the equivalence chemically necessary addition addition, added in the step finished homogenizing , is mixed. 3. A process for the preparation of a bicarbonate-containing electrolyte according to item 2 / characterized in that preferably used as solid organic acids with pK _s = 5 adipic acid, citric acid, aspartic acid and glutamic acid alone or in the form of a mixture of 2 ... 4 of the aforementioned acids become.