RU2536994C1 - Concentrated acidic component, kit for producing it, concentrated solution of acidic component for producing hemodialysis solution and method for producing it - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a concentrated acidic component for producing a hemodialysis solution. The acidic component contains the following ingredients in an amount of producing 1 litre of the solution in water purified for hemodialysis: 204.7-215.0 g of sodium chloride NaCl, 6.2-9.0 g of calcium chloride CaCl₂*2H₂O, 3.56-7.12 g of magnesium chloride MgCl₂*6H₂O, 5.22-10.44 g of potassium chloride KCl, 0.021-6.28 g of acetic acid and 0.02-6.2 g of succinic acid. Also, the invention refers to the hemodialysis solution containing the above concentrated acidic component, water purified for hemodialysis, and bicarbonate component. The invention also refers to a method for producing the hemodialysis solution with the method involving supplying the concentrated acidic component into a hemodialysis apparatus, diluting with water purified for hemodialysis, and mixing with bicarbonate component. What is also declared is a kit for producing the concentrated acidic component containing sodium chloride, calcium chloride, magnesium chloride, potassium chloride, succinic acid in the form of dry agents and acetic acid in the form of a liquid agent.

EFFECT: invention provides higher effectiveness by a biochemical compatibility with blood plasma of the hemodialysis solution.

36 cl, 18 tbl, 16 ex

Description

FIELD OF TECHNOLOGY

The invention relates to medicine, in particular to compositions of hemodialysis solutions for bicarbonate hemodialysis, which can be used in clinical practice for extracorporeal blood purification for the treatment of patients with acute and chronic renal failure.

BACKGROUND

In the practice of hemodialysis, acetic acid (3–9 mmol / L) is traditionally used, the concentration of which is many times higher than the physiological concentration in the blood plasma (0.05–0.1 mmol / L), which causes acetamia and a number of other adverse consequences. At the same time, acetate is a natural and necessary substrate of the body: acetyl coenzyme A is the main energy metabolite located in the very center of the metabolism of carbohydrates, proteins and lipids.

Known acid component for hemodialysis, including lactic, malic, citric, acetic acids [US 2010/055963, A1, 2010].

Known acid concentrate, including lactic, acetic, citric acids [US 6251437 B1, 03/03/2002]. However, in these inventions, various acids were used to regulate the pH, to reduce acetate ions in the hemodialysis solution, and to prevent acetamia.

The disadvantages of the known substances include the fact that the introduction of organic and inorganic acids was aimed at pH regulation, their concentration and ratio in the hemodialysis solution were not optimized and did not correlate with the possible therapeutic effect during the chronic hemodialysis procedure.

Known hemodialysis solutions for bicarbonate hemodialysis [RU 2435567, 2011; RU 2311202, 2006; RU 2438663, 2010], which reduced acetamia in patients, a therapeutic effect was also observed from the introduction of organic acids into the hemodialysis solution.

The hemodialysis solution obtained by the method described in patent RU No. 2311202 contains the following components, mmol / l: sodium chloride NaCl 137.3-140.3, calcium chloride CaCl ₂ * 2H ₂ O 1.2-1.75, magnesium MgCl ₂ * 6H ₂ O 0.5-1.0 chloride, potassium chloride KCl 0.3-4.0, glucose (g / l) 1.0-5.0, sodium acetate 0.3, citric acid 0, 1-0.7, succinic acid C ₄ H ₆ O ₄ 1.1-0.1. The hemodialysis solution obtained by the method described in RF patent No. 2438663, 2010, contains the following components, mmol / l: sodium chloride NaCl 137.3-140.3, calcium chloride CaCl ₂ * 2H ₂ O 1.2-1.75 magnesium chloride MgCl ₂ * 6H ₂ O 0.5-1.0, potassium chloride KCl 0.3-4.0, glucose (g / l) 1.0-5.0, hydrochloric acid 0.1-2, 9, succinic acid C ₄ H ₆ O ₄ 0.1-2.9.

The disadvantages of the known hemodialysis solutions obtained by the method described in patents RU No. 2311202, No. 2438663, is the low biocompatibility of the solution with the patient's body due to its high osmolarity (318-328 mosm / l), exceeding the physiological osmolarity of human blood (280- 310 mosm / l). The high osmolarity of the hemodialysis solutions obtained by the method described in these patents is due to the increased content of sodium and chlorine ions and glucose in the known solutions, which are involved in maintaining the osmolarity of the hemodialysis solution and the regulation of water-salt metabolism. The solutions used did not have a persistent positive effect and led to side effects in the chronic hemodialysis procedure due to low biocompatibility. Patients increased pressure, a deterioration in the quality of life was noted - thirst, itching, etc.

The hemodialysis solution obtained by the method described in patent RU 2435567 contains the following components, mmol / l: sodium chloride NaCl 137.3-140.3, calcium chloride CaCl ₂ * 2H ₂ O 1.2-1.75, magnesium chloride MgCl ₂ * 6H ₂ O 0.5-1.0, potassium chloride KCl 0.3-4.0, glucose (g / l) 1.0-5.0, acetic acid 0.1-2.9, succinic acid C ₄ H ₆ C ₄ 0.1-2.9, sodium bicarbonate 32.0.

Table 1 shows the qualitative and quantitative characteristics of the compositions described in examples 1-3 of patent RU 2435567, adopted as a prototype of the proposed method and hemodialysis solution for bicarbonate hemodialysis, obtained from concentrated acid and bicarbonate components, by dilution and subsequent mixing in the apparatus “artificial bud".

Table 1 Name of ion, mmol / l The values of the indicators when using the compositions described in patent RU 2435567 example 1 example 2 example 3 Sodium Chloride 137.3 140.3 140.3 Calcium chloride 1,2 1.75 1.75 Potassium chloride 0.5 1,0 4.0 Magnesium chloride 0.3 2.0 1,0 Chlorine 105.8 113.8 114.5 Acetate 0.1 2.9 2.2 Succinate 2.9 0.1 0.8 Citrate - - - Hydrochloric acid - - - Bicarbonate* 32 32 32 bicarbonate ions 32 sodium ions 35 Glucose, g / l * 5,0 1,0 1,0 Theoretical osmolarity, mosm / l 318 328 339

The disadvantages of the known hemodialysis solution obtained by the method described in patent RU 2435567 is the low biocompatibility of the solution with the patient’s body due to its high osmolarity (318-328 mosm / l), exceeding the physiological osmolarity of human blood (280-310 mosm / l ) The high osmolarity of the hemodialysis solution obtained by the method described in patent RU 2435567 is due to the increased content of sodium and chlorine ions and glucose in the known solution, which are involved in maintaining the osmolarity of the hemodialysis solution and the regulation of water-salt metabolism.

The task to which the group of inventions is directed is to create a new composition of a hemodialysis solution for bicarbonate hemodialysis, biocompatible with blood plasma, containing a mixture of organic and inorganic acids, combining the functions of pH regulation and the function of the general metabolic effect on the patient's body during the chronic hemodialysis procedure.

The main problem is the amount of the same name organic acid in the dialysis solution, because the body must metabolize the organic acid anion, the concentration of which significantly exceeds its physiological concentration in the blood plasma, which when replacing one acid with another, for example, acetic acid with succinic acid, leads to complications similar to acetamia. To solve this problem, we proposed to reduce the acetate content in the dialysis solution by replacing part of the acetic acid with succinic acid. In order to further reduce the concentration of acetic and succinic acids to more optimal values, part of the acetic and succinic acids was replaced by inorganic hydrochloric acid. An additional introduction to the hemodialysis solution of citric acid increases the efficiency of hemodialysis, due to the binding of calcium ions it prevents thrombosis of the dialyzer capillaries, and the efficiency from the use of succinic acid increases.

The technical result achieved by using the group of inventions is to increase the efficiency of the hemodialysis procedure by biochemical compatibility with the blood plasma of the hemodialysis solution and optimize its composition while increasing the therapeutic effect and the absence of side effects in the patient.

The achievement of the technical result is ensured by the optimally balanced qualitatively quantitative composition of the components given in the formula, which makes it possible to bring the osmolarity of the hemodialysis solution into account with the osmolarity of human blood plasma, which ensures high dialysis efficiency with a therapeutic effect.

Disclosure of invention

To solve the problem and achieve the technical result, a group of inventions is proposed, united by a common inventive concept.

One of the aspects of the invention is a concentrated acid component for producing a hemodialysis solution, including sodium chloride, calcium chloride, magnesium chloride, potassium chloride, succinic acid and acetic acid, characterized in that the amount of these components, calculated to obtain 1 liter of solution in purified for hemodialysis water is, g:

sodium chloride NaCl 204.7-215.0 calcium chloride CaCl ₂ * 2H ₂ O 6.2-9.0 magnesium chloride MgCl ₂ * 6H ₂ O 3.56-7.12 potassium chloride KCl 5.22-10.44 acetic acid C ₂ H ₄ O ₂ 0.021-6.28 succinic acid C ₄ H ₆ O ₄ 0.02-6.2

According to the invention, the concentrated acid component further comprises citric acid C ₆ H ₈ O ₇ in an amount of from 0.022 to 7.3 g.

According to the invention, the concentrated acid component further comprises hydrochloric acid HCl in an amount of from 0.012 to 3.8 g.

According to the invention, the acid component further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 76.0 g.

According to the invention, in the concentrated acid component, the total amount of all acids is 105 meq / l.

The next aspect of the invention is a concentrated solution of the acid component to obtain a hemodialysis solution, including sodium chloride, calcium chloride, magnesium chloride, potassium chloride, acetic acid, succinic acid in dissociated form in the following amount, meq / l:

sodium ions Na ⁺ 3500.0-3675.0 calcium ions Ca ²⁺ 84.0-122.5 magnesium ions Mg ²⁺ 5.0-70.0 potassium ions K ⁺ 70.0-140.0 chlorine ions Cl ^- 3710.0-3937.5 acetate ions C ₂ H ₃ O ^2- 0.35-104.65 succinate ions C ₄ H ₄ O ₄ ^2- 0.35-104.65

присутствуют в количестве от 0,35 до 104,3 мэкв/л.According to the invention, a concentrated solution of an acid component, further comprising citric acid in dissociated form, where citrate ions

present in an amount of 0.35 to 104.3 meq / l.

According to the invention, the concentrated solution of the acid component further comprises hydrochloric acid in dissociated form, in which the content of chloride ions Cl ^- is from 0.35 to 104.3 meq / l.

According to the invention, the concentrated solution of the acid component further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 420 mmol / L.

According to the invention, the concentrated solution of the acid component further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 420 mmol / L.

According to the invention, in a concentrated solution of the acid component, the total amount of all acids is 105 meq / l.

Another aspect of the invention is a hemodialysis solution comprising a concentrated solution of an acid component, water purified for hemodialysis, or a concentrated solution of an acid component, water purified for hemodialysis, and a bicarbonate component.

According to the invention, the hemodialysis solution has the following composition, meq / l:

sodium ions Na ⁺ 135.0-140.0 calcium ions Ca ²⁺ 2.4-3.5 magnesium ions Mg ²⁺ 1.0-2.0 potassium ions K ⁺ 2.0-4.0 chlorine ions Cl ^- 106.0-112.5

acetate ions

0.01-2.99 succinate ions

0.01-2.99 bicarbonate ions

27.0-40.0

в количестве от 0,01 до 2,98 мэкв/л.According to the invention, the hemodialysis solution further comprises citrate ions

in an amount of from 0.01 to 2.98 meq / l.

According to the invention, the hemodialysis solution additionally contains chloride Cl ions ^- in an amount of from 0.01 to 2.98 meq / l:

According to the invention, the hemodialysis solution further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 12.0 mmol / L.

According to the invention, the hemodialysis solution also has the following composition, meq / l:

sodium ions Na + 138.0 calcium ions Ca ₂ ⁺ 3,5 magnesium ions Mg ₂ ⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions C ₂ H ₃ O ^2- 0.3 succinate ions C ₄ H ₄ O ₄ ^2- 0.7 chlorine ions (from hydrochloric acid) 1,5 citrate ions 0.5 bicarbonate ions HCO ₃ ^- 32,0

According to the invention, the hemodialysis solution also has the following composition, meq / l:

sodium ions Na ₊ 138.0 calcium ions Ca ₂ ⁺ 3,5 magnesium ions Mg ₂ ⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions C ₂ H ₃ O ^2- 0.3 succinate ions C ₄ H ₄ O ₄ ^2- 0.8 chlorine ions (from hydrochloric acid) 1.4 citrate ions 0.5 bicarbonate ions HCO ₃ ^- 32,0

According to the invention, the hemodialysis solution also has the following composition, meq / l:

sodium ions Na ⁺ 138.0 calcium ions Ca ₂ ⁺ 3,5 magnesium ions Mg ₂ ⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions C ₂ H ₃ O ^2- 0.2 succinate ions C ₄ H ₄ O ₄ ^2- 1,0 chlorine ions (from hydrochloric acid) 1,5 citrate ions 0.3 bicarbonate ions HCO ₂ ^- 32,0

According to the invention, the hemodialysis solution also has the following composition, meq / l:

sodium ions Na ⁺ 138.0 calcium ions Ca ₂ ⁺ 3,5 magnesium ions Mg ₂ ⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions C ₂ H ₃ O ^2- 0.1 succinate ions C ₄ H ₄ O ₄ ^2- 0.7 chlorine ions (from hydrochloric acid) 1,2 citrate ions 0.7 bicarbonate ions HCO ₃ ^- 32,0

According to the invention, the hemodialysis solution may further include glucose in an amount of 5.5 mmol / L.

Another aspect of the invention is a method for producing a hemodialysis solution according to any of the compositions, comprising feeding a concentrated acid component according to the invention or a concentrated solution of an acid component according to the invention to a hemodialysis apparatus, diluting it with purified hemodialysis water, and mixing with a bicarbonate component.

According to the invention, the hemodialysis solution obtained by the proposed method has the following composition, meq / l:

sodium ions Na ⁺ 135.0-140.0 calcium ions Ca ₂ ⁺ 2.4-3.5 magnesium ions Mg ₂ ⁺ 1.0-2.0 potassium ions K ⁺ 2.0-4.0 chlorine ions Cl ^- 106.0-112.5 acetate ions C ₂ H ₃ O ₂ ^- 0.01-2.99 succinate ions C ₄ H ₄ O ₄ ^2- 0.01-2.99 bicarbonate ions HCO ₃ ^- 27.0-40.0

Another aspect of the invention is a kit for producing a concentrated acid component according to the invention or a solution of a concentrated acid component according to the invention, including sodium chloride, calcium chloride, magnesium chloride, potassium chloride, succinic acid in the form of dry reagents and acetic acid in the form of a liquid reagent, characterized in that the amount of these components, based on to obtain 1 liter of solution in purified water for hemodialysis, is, g:

sodium chloride NaCl 204.7-215.0 calcium chloride CaCl ₂ * 2H ₂ O 6.2-9.0 magnesium chloride MgCl ₂ * 6H ₂ O 3.56-7.12 potassium chloride KCl 5.22-10.44 acetic acid C ₂ H ₄ O ₂ 0.021-6.28 succinic acid C ₄ H ₆ O ₄ 0.02-6.2

According to the invention, the kit further comprises citric acid C ₆ H ₈ O ₇ in an amount of from 0.022 to 7.3 g.

According to the invention, the kit further comprises citric acid in the form of a dry reagent.

According to the invention, the kit further comprises hydrochloric acid HCl in an amount of from 0.012 to 3.8 g.

According to the invention, the kit further comprises hydrochloric acid in the form of a liquid reagent.

According to the invention, the kit further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 76.0 g / l.

According to the invention, the dry reagents in the kit can be in the form of a mixture and / or in the form of a set of individual components.

Each form of concentrate production — from dry reagents or from liquid ones — can be carried out separately without regard to the rest. Thus, the formation of a set / mixture of dry salts can lead to a commercial kit in which all components are in dry form, with the exception of those that under normal conditions cannot be represented as a dry substance, for example, acetic, hydrochloric acid.

The concentrated acid component can be obtained from such a set in appropriate apparatuses, poured into containers for subsequent use.

Hemodialysis solution can be obtained by diluting concentrated solutions using standard equipment, it is customary to prepare such concentrates that are subject to standard dilution. For example, an acid concentrate is mixed with purified water for hemodialysis in an “artificial kidney” apparatus in a standard ratio of 1:35 or 1:44, although other dilution schemes are possible.

A standard dilution of 1:35 implies: 1 liter of liquid concentrated acid component A, 1.225 liters of 8.4% bicarbonate component B, 32.775 liters of purified water for hemodialysis.

A significant difference of the claimed group of inventions is the optimized, in accordance with the task, composition of the concentrated acid component, the concentrated solution of the acid component obtained by diluting the acid component concentrate purified for hemodialysis with water, the hemodialysis solution obtained by dilution and mixing with a bicarbonate solution, optimally balanced in in accordance with the quantitative characterization of the component ratios given in the formula acteristic providing osmolarity administered to a patient gemodializiruyuschego solution approximate to that of human blood plasma osmolarity, increase efficiency of hemodialysis, while achieving a therapeutic effect.

It is important to note that the change in the quantitative range of sodium chloride values in the acid component from 204.7 g / l to 215.0 g / l, and accordingly sodium ions in a concentrated solution from 3500 to 3675 meq / l, and in a hemodialysis solution from 135 meq / l to 140 meq / l; as well as a change in the quantitative interval of glucose in the acid component from 0 to 76 g (in dry form) and, accordingly, in a concentrated hemodialysis solution from 0 to 420 mmol / L and diluted from 0 to 12 mmol / L, values of other components balanced with quantitative intervals, provides the osmolarity of the hemodialysis solution administered to the patient, which is close to the osmolarity of human blood plasma.

Replacing a portion of acetic acid and / or succinic acid with hydrochloric and / or citric acid and optimizing the ratio of acids can further increase the effectiveness of the hemodialysis procedure and obtain an unexpected therapeutic effect without side complications in the patient.

SUMMARY OF THE INVENTION

Two concentrated solutions are used for bicarbonate hemodialysis: the acid component (A) and the bicarbonate component (B), the solution of which can be replaced with a bicarbonate cartridge containing dry sodium bicarbonate reagent. Dilution and mixing of concentrates (A) and (B) and the formation of a hemodialysis solution occurs in the hemodialysis apparatus (dialysis machine, artificial kidney apparatus), which collects the concentrated components A and B with their subsequent dilution and mixing. The bicarbonate component contains sodium bicarbonate, which acts as a blood buffer, which must be replenished by patients on hemodialysis. Typically, the concentrated bicarbonate component contains 84 g / l (1000 meq / l) of sodium bicarbonate NaHCO ₃ . In modern "artificial kidney" devices, the modes of functioning are determined and set by the operator before the start of the session, depending on the condition of the patient and can change during the entire hemodialysis procedure. Since standard equipment is used to dilute concentrates, it is customary to prepare concentrates that are subject to standard dilution. For example, an acid concentrate is mixed with water in a hemodialysis machine in a standard ratio of 1:35, although other dilution schemes are possible.

Depending on the clinical characteristics of the patient, the acid component may or may not contain glucose. The claimed acid component may contain glucose C ₆ H ₁₂ O ₆ in an amount of not more than 76 g.

The acid component must contain acid to establish the pH after mixing with the bicarbonate component in the range of 7.3 to 7.4 in order to prevent calcium from precipitating on the surface of the hemodialysis equipment. The concentration of the injected acid or mixture of acids is usually 3 meq / l in the hemodialysis solution. The “Acid component” and “Bicarbonate component”, from which the hemodialysis solution for bicarbonate dialysis is obtained, may be in the form of concentrates (acid component concentrate, bicarbonate component concentrate). After dilution of the “acid concentrate”, a dilute acid component is obtained.

Purified hemodialysis water (demineralized water) is used to dilute the concentrates.

The qualification of the chemicals used to dissolve and then dilute the concentrated solutions must comply with international, regional or national standards developed for hemodialysis solutions (Composition and Management of Hemodialysis Fluids. Pubst Science Publishers Lengerich, Berlin, Riga, Rom, Wien, Zagreb.p.l4) . To obtain a therapeutic effect, with the aim of carrying out metabolic hemodialysis, by introducing into the solution organic acids - succinic, citric, leading to the intensification of the Krebs cycle, the acetic acid traditionally included in the acid component is partially replaced by succinic acid.

The proposed composition of the acid component may additionally contain citric acid C ₆ H ₈ O ₇ in an amount of from 0.022 to 7.3 g. The introduction of citric acid into the solution improves the dialysis efficiency by preventing thrombosis of the membrane fibers, which in combination with succinic acid increases quality of the dialysis procedure.

The proposed composition of the acid component may additionally also contain hydrochloric acid HCl in an amount of from 0.012 to 3.8 g. Introduction of hydrochloric acid into the solution allows to reduce the concentration of succinic, acetic and citric acids, the concentration of which is close to physiological, thereby increasing the biocompatibility of the hemodialysis solution to plasma blood, which avoids side complications due to the high concentration of acid of one name.

The total amount of all acids in the concentrated acid component is 105 meq / l, which is necessary to maintain the pH of the solution.

Thus, the proposed preferred combination of acids additionally gives a synergistic effect, demonstrating an advantage over using each acid separately. Reducing acidosis by replacing part of acetic acid with hydrochloric acid leads to an increase in the efficiency of the hemodialysis procedure. Introduction to the composition of citric acid leads to increased effectiveness of the effect on the patient's body of succinic acid.

The essence of the group of inventions is illustrated by examples in which Tables 2-17 show the qualitative and quantitative characteristics of dry and liquid concentrates of the acid component and the hemodialysis solution obtained according to the invention. The data in Tables 2-17 are provided to illustrate certain aspects of the implementation of the group of inventions and are not intended to limit the scope of the present group of inventions in any way.

Example. one

To obtain a hemodialysis solution, the composition of which is shown in Table 2, dry reagents are taken in the amounts shown in column 2, dissolved in water purified for hemodialysis and a concentrated hemodialysis solution is obtained, the composition of which corresponds to the data given in column 3. The bicarbonate component is taken in the form concentrated 8.4% (1000 meq / l) sodium bicarbonate solution NaHCO ₃ or prepare it from a dry reagent (8.4 kg sodium bicarbonate) by dissolving it with purified water for hemodialysis. To obtain a hemodialysis solution, a container with a concentrated acid component and a container with a concentrated bicarbonate component (in dry or liquid form) are connected to a hemodialysis device, which automatically dilutes in a predetermined ratio, for example, at a standard dilution of 1:35. In this case, the acid component (A) is diluted 35 times, the bicarbonate component (B) 28.6 times and mixes the components (A) and (B). The composition of dry and liquid concentrates and hemodialysis solution are presented in table 2.

table 2 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 215.0 Sodium ion 3675.0 140.0 Calcium chloride 6.4 Calcium ion 87.5 2,5 Potassium chloride 10,4 Potassium ion 140.0 4.0 Magnesium chloride 3.6 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3937.5 112.5 Acetic acid 0,021 Acetate Ion 0.35 0.01 succinic acid 6.2 Succinate ion 104.65 2.99 Lemon acid - Citrate - - Hydrochloric acid - Chlorine ion - - Glucose - - Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32 Theoretical osmolarity, mosm / l 295

When diluted acid (A) and bicarbonate (B) components are mixed in HDA, a neutralization reaction occurs: 3 meq / l of hydrogen ions are neutralized from 35 meq / l of sodium bicarbonate, 3 meq / l of hydrogen ions, but 35 meq / l of sodium ions remain in the solution . As a result, the content of sodium ions after mixing components (A) and (B) increases by 35 meq / l, the composition of the hemodialysis solution will correspond to the composition shown in Table 2.

The resulting composition of the hemodialysis solution (hereinafter GDR) has an osmolarity of 295 mosm / l, which is close in value to the osmolarity of human blood plasma, which makes it more biocompatible with blood plasma and allows to obtain a therapeutic effect from the acid mixture introduced into the hemodialysis solution.

Example 2

The preparation of the hemodialysis solution of Example 1 is repeated, but with a quantitative ratio of components different from Example 1 and additionally containing glucose (Table 3).

Table 3 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 204.7 Sodium ion 3,500.0 135.0 Calcium chloride 9.0 Calcium ion 122.5 3,5 Potassium chloride 5.2 Potassium ion 70.0 2.0 Magnesium chloride 7.12 Magnesium ion 70.0 2.0 Chlorine (from salts) - Chlorine ion 3762.5 107.5 Acetic acid 6.28 Acetate Ion 104.65 2.99 succinic acid 0.02 Succinate ion 0.35 0.01 Lemon acid - Citrate - - Hydrochloric acid - Chlorine ion - - Glucose 35.0 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32 Theoretical osmolarity, mosm / l 290

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity of 290 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma and to obtain the therapeutic effect of the administration of small amounts of succinic acid in the hemodialysis chronic procedure .

Example 3

The preparation of the hemodialysis solution of Example 1 is repeated, but with a quantitative ratio of components different from Example 1 and additionally containing glucose (Table 4).

Table 4 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 6.2 Calcium ion 84.0 2,4 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3846.5 109.9 Acetic acid 4.4 Acetate Ion 74,2 2.12 succinic acid 1.8 Succinate ion 30.8 0.88 Lemon acid - Citrate - - Hydrochloric acid - Chlorine ion - - Glucose 35.0 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32 Theoretical osmolarity, mosm / l 295.3

The resulting composition of the GDR, containing a mixture of acids and having an osmolarity of 295.3 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, and 30% replacement of acetic acid with succinic acid can reduce the amount ions of acetate and get in the chronic hemodialysis procedure the therapeutic effect of the introduction of succinic acid.

Example 4

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different proportion of components and additionally containing glucose, different from Example 1 (Table 5).

Table 5 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 7.8 Calcium ion 105.0 3.0 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3867.5 110.5 Acetic acid 3.8 Acetate Ion 63.0 1.8 succinic acid 2,5 Succinate ion 42.0 1,2 Lemon acid - Citrate - - Hydrochloric acid - Chlorine ion - - Glucose 35.0 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32 Theoretical osmolarity, mosm / l 296.5

The resulting composition of the GDR, containing a mixture of acids and having an osmolarity of 296.5 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, and 40% replacement of acetic acid with succinic acid can significantly reduce the amount of acetate ions and get the therapeutic effect of the administration of succinic acid in the chronic hemodialysis procedure.

Example 5

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing hydrochloric acid (Table 6).

Table 6 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 7.2 Calcium ion 98.00 2,8 Potassium chloride 10.44 Potassium ion 140.0 4.0 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3878,0 110.8 Acetic acid 0.2 Acetate Ion 0.35 0.01 succinic acid 1.4 Succinate ion 23.8 0.68 Lemon acid - Citrate - - Hydrochloric acid 0.29 Chlorine ion 80.5 2,3 Glucose Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32 Theoretical osmolarity, mosm / l 292

The obtained composition of HDA, containing a mixture of acids and having an osmolarity of 292 mosm / l, which is close in value to the osmolarity of human blood plasma, improves the biocompatibility of the hemodialysis solution to blood plasma, and the replacement of acetic acid with hydrochloric acid with the addition of small amounts of succinic acid allows reduce the number of acetate ions by 99.6% and get the therapeutic effect of removing acetate ions and the introduction of small amounts of succinic acid in the chronic hemodialysis procedure.

Example 6

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing glucose and hydrochloric acid (Table 7).

Table 7 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 215.0 Sodium ion 3675.0 138.0 Calcium chloride 7.2 Calcium ion 98.00 3.0 Potassium chloride 6.5 Potassium ion 87.5 2,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3832.5 109.5 Acetic acid 0.2 Acetate Ion 0.35 1.49 succinic acid 0.02 Succinate ion 0.35 1,5 Lemon acid - Citrate - - Hydrochloric acid 0.012 Chlorine ion 0.35 0.01 Glucose 35.0 - 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 295

The resulting composition of the GDR, containing a mixture of acids and having an osmolarity of 295 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, and the replacement of 49.6% of acetic acid with succinic acid with the addition of 0 , 3% succinic acid allows you to reduce the number of acetate ions by 50% and get in the chronic hemodialysis procedure a therapeutic effect from the removal of acetate ions and the introduction of succinic acid.

Example 7

In a preferred embodiment of the invention, the preparation of the hemodialysis solution of Example 1 is repeated, but with a different proportion of components from the component and additionally containing glucose and hydrochloric acid (Table 8).

Table 8 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 9.0 Calcium ion 122.5 3,5 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3885.0 111.0 Acetic acid 1.0 Acetate Ion 17.5 0.5 succinic acid 2.1 Succinate ion 35.0 1,0 Lemon acid - Citrate - - Hydrochloric acid 1.9 Chlorine ion 52,5 1,5 Glucose 35.0 - 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32 Theoretical osmolarity, mosm / l 297

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity equal to 297 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, hydrochloric, succinic acids in this embodiment is preferred and allows you to get the most pronounced therapeutic effect of the hemodialysis procedure.

Example 8

In a preferred embodiment of the invention, the preparation of the hemodialysis solution of Example 1 is repeated, but with a different proportion of components from the component and additionally containing hydrochloric acid (Table 9).

Table 9 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 6.4 Calcium ion 87.5 2,5 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 4.6 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3850.0 110.0 Acetic acid 0.42 Acetate Ion 7.0 0.2 succinic acid 1,6 Succinate ion 28.0 0.8 Lemon acid - Citrate - - Hydrochloric acid 2,5 Chlorine ion 70.0 2.0 Glucose - - - - Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 290

The resulting composition of the GDR, containing a mixture of acids and having an osmolarity equal to 290 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, hydrochloric, succinic acids in this embodiment is preferred and allows you to get the most pronounced therapeutic effect of the hemodialysis procedure.

Example 9

In a preferred embodiment of the invention, the preparation of the hemodialysis solution of Example 1 is repeated, but with a different proportion of components from the component and additionally containing citric acid and glucose (Table 10).

Table 10 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 7.7 Calcium ion 105 3.0 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3867.5 110.5 Acetic acid 0.2 Acetate Ion 0.35 0.01 succinic acid 0.02 Succinate ion 0.35 0.01 Lemon acid 7.3 Citrate 104.3 2.98 Hydrochloric acid - Chlorine ion - - Glucose 35.0 - 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 296

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity of 296 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively-quantitative mixture of citric acid with a small addition of acetic, succinic acid allows you to use it for patients with heparin intolerance in the chronic hemodialysis procedure to obtain a therapeutic effect from the procedure.

Example 10

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing citric acid and glucose (Table 11).

Table 11 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 7.7 Calcium ion 105.0 3.0 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3867.5 110.5 Acetic acid 3.13 Acetate Ion 52.15 1.49 succinic acid 3,1 Succinate ion 52,5 1,5 Lemon acid 0.02 Citrate 0.35 0.01 Hydrochloric acid - Chlorine ion - - Glucose 35.0 - 194.25 mmol / L 5.5 5 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 297

The resulting composition of the GDR, containing a mixture of acids and having an osmolarity equal to 297 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, succinic acid with a small amount of citric acid Compared with conventional dialysis, it leads to an increase in the dose of dialysis, obtaining a therapeutic effect from the hemodialysis procedure.

Example 11

In a preferred embodiment of the invention, the preparation of the hemodialysis solution of Example 1 is repeated, but with a different proportion of components and additionally containing citric acid from Example 1 (Table 12).

Table 12 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 9.0 Calcium ion 122.5 3,5 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3885.0 111.0 Acetic acid 2.7 Acetate Ion 45.5 1.3 succinic acid 2.1 Succinate ion 35.0 1,0 Lemon acid 1.7 Citrate 24.5 0.7 Hydrochloric acid - Chlorine ion - - Glucose - - - - Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 292

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity of 292 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, succinic, citric acids in comparison with conventional dialysis leads to an increase in the effectiveness of the hemodialysis procedure (increasing the dialysis dose, facilitating the re-dialysis of dialyzers) in combination with the therapeutic effect of the procedure.

Example 12

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing citric acid and glucose (Table 13).

Table 13 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 6.2 Calcium ion 84.0 2,4 Potassium chloride 5.22 Potassium ion 70.0 2.0 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3794.0 108,4 Acetic acid 2.1 Acetate Ion 35.0 1,0 succinic acid 3.2 Succinate ion 35.0 1,5 Lemon acid 2.1 Citrate 17.5 0.5 Hydrochloric acid - Chlorine ion - - Glucose 69.3 - 385.0 mmol / L 11.0 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 298

The resulting composition of the GDR, containing a mixture of acids and having an osmolarity equal to 298 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, succinic, citric acids in comparison with conventional dialysis leads to an increase in the effectiveness of the hemodialysis procedure (increasing the dialysis dose, facilitating the dialysis dialysis re-use) in combination with the therapeutic effect of the procedure. The addition of glucose prevents episodes of asymptomatic hypoglycemia in patients on chronic hemodialysis using metabolic hemodialysis, which requires significant amounts of glucose, due to the activation of the Krebs cycle.

Example 13

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing citric acid, hydrochloric acid and glucose (Table 14).

Table 14 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 7.7 Calcium ion 105.0 3.0 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1.0 Chlorine (from salts) - Chlorine ion 3867.5 110.5 Acetic acid 0.42 Acetate Ion 7.0 0.2 succinic acid 2.07 Succinate ion 35.0 1,0 Lemon acid 0.74 Citrate 10.5 0.3 Hydrochloric acid 1.9 Chlorine ion 52,5 1,5 Glucose 35.0 - 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 297

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity equal to 297 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, succinic, citric, hydrochloric acids Compared with conventional dialysis, it increases the efficiency of the hemodialysis procedure (increasing the dialysis dose, facilitating the dialysis dialyses rejuvenation) in combination with the therapeutic effect of the procedure. The introduction of hydrochloric acid in an amount of 50% allows you to significantly bring the content of organic acids to their physiological concentration in blood plasma. The addition of glucose prevents episodes of asymptomatic hypoglycemia in patients on chronic hemodialysis using metabolic hemodialysis.

Example 14

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing citric acid, hydrochloric acid and glucose (Table 15).

Table 15 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 7.7 Calcium ion 105.0 3.0 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3867.5 110.5 Acetic acid 1.05 Acetate Ion 17.5 0.5 succinic acid 1,6 Succinate ion 28.0 0.8 Lemon acid 0.5 Citrate 7.0 0.2 Hydrochloric acid 1.9 Chlorine ion 52,5 1,5

one 2 3 four 5 Glucose 35.0 - 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 297

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity of 297 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, succinic, citric acids in comparison with conventional dialysis leads to an increase in the effectiveness of the hemodialysis procedure (increasing the dialysis dose, facilitating the dialysis dialysis re-use) in combination with the therapeutic effect of the procedure. The addition of glucose prevents episodes of asymptomatic hypoglycemia in patients on chronic hemodialysis using metabolic hemodialysis.

Example 15

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing citric acid, hydrochloric acid and glucose (Table 16).

Table 16 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 9.0 Calcium ion 122.5 3,5 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3867.5 110.5 Acetic acid 2.1 Acetate Ion 35.0 1,0

one 2 3 four 5 succinic acid 2,3 Succinate ion 38.5 1,1 Lemon acid 1.7 Citrate 24.5 0.7 Hydrochloric acid 0.25 Chlorine ion 7.0 0.2 Glucose 35.0 - 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 297

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity equal to 297 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, succinic, citric acids, hydrochloric acid compared with conventional dialysis, it leads to an increase in the efficiency of the hemodialysis procedure (increase in dialysis dose, facilitating dialyzer reuse) in combination with the therapeutic effect of the procedure. The addition of glucose prevents episodes of asymptomatic hypoglycemia in patients on chronic hemodialysis using metabolic hemodialysis.

Example 16

The preparation of the hemodialysis solution of Example 1 is repeated, but with a different quantitative ratio of components and additionally containing citric acid, hydrochloric acid and glucose (Table 17).

Table 17 Name of indicator Dry salt set Name of indicator Concentrated solution Dialysis solution Content, g / l Content, meq / l one 2 3 four 5 Sodium Chloride 210.9 Sodium ion 3605.0 138.0 Calcium chloride 9.0 Calcium ion 122.5 3,5

one 2 3 four 5 Potassium chloride 9.1 Potassium ion 122.5 3,5 Magnesium chloride 3.56 Magnesium ion 35.0 1,0 Chlorine (from salts) - Chlorine ion 3885.5 111.0 Acetic acid 2.7 Acetate Ion 45.5 1.3 succinic acid 1,6 Succinate ion 28.0 0.8 Lemon acid 1,2 Citrate 17.5 0.5 Hydrochloric acid 0.5 Chlorine ion 14.0 0.4 Glucose 35.0 - 194.25 mmol / L 5.55 mmol / L Bicarbonate of soda 84.0 Bicarbonate ion 1000,0 32,0 Theoretical osmolarity, mosm / l 297

The obtained composition of the GDR, containing a mixture of acids and having an osmolarity of 297 mosm / l, which is close in value to the osmolarity of human blood plasma, can increase the biocompatibility of the hemodialysis solution to blood plasma, a qualitatively quantitative mixture of acetic, succinic, citric acids in comparison with conventional dialysis leads to an increase in the effectiveness of the hemodialysis procedure (increasing the dialysis dose, facilitating the dialysis dialysis re-use) in combination with the therapeutic effect of the procedure. The addition of glucose prevents episodes of asymptomatic hypoglycemia in patients on chronic hemodialysis using metabolic hemodialysis.

In contrast to the GDR obtained by the method described in RF patent No. 2435567, the osmolarity index, which depends on the content of all ions included in the hemodialysis solution, which is 318-339 mosm / l (see Table 1), the osmolarity of the proposed solution are ranging from 287 mosm / l to 298 mosm / l (see Tables 2-17).

The achieved osmolarity indices of the proposed GDR correspond to the osmolarity indices of human blood plasma, due to which an increase in biochemical compatibility with the patient’s body is achieved, which in turn makes it possible to increase the effectiveness of the therapeutic effect of the mixture of organic and inorganic acids introduced into the composition of the HDA.

In the process of research it was found that the effect of the use of hemodialysis compounds containing succinic acid depends on its concentration, which should be close to physiological. The acid introduced into the GDR performs the function of a pH regulator, exceeding which above 7.3-7.4 leads to the precipitation of calcium-magnesium precipitation. In order to maintain the function of the pH regulator of the solution, part of the acetic acid is replaced with hydrochloric acid, which reduces the concentration of acetic and succinic acids to optimal values.

The introduction of inorganic hydrochloric acid can reduce the concentration of organic acids and the main function of hemodialysis is the removal of toxins, transfer to metabolic hemodialysis, i.e. get various significant therapeutic effects.

In addition, as can be clearly seen from examples 1-16, the quantitative range of sodium ions was significantly reduced from 135 meq / l to 140 meq / l in the GDR compared with the prototype (patent No. 2435567) 172.3-175.3 mmol / l. The upper glucose interval is reduced, which is also involved in the osmolarity of the solution from 27.75 mmol / l (5 g / l in the prototype patent RU 2435567) to 12 mmol / l, balanced with quantitative intervals of the values of other components, ensures the osmolarity of the hemodialysis solution introduced to the patient close to the osmolarity of human blood plasma.

To test the action of solutions, cross-sectional studies were conducted with 2 groups of patients: control (n = 40) and experimental (n = 55). Both groups did not differ in age, gender, primary initial pathology, duration of hemodialysis treatment, or the nature of the concomitant pathology.

For 6 months, the control group received hemodialysis sessions using standard HDA with acetic acid, in the experimental group sessions were conducted using the solutions of the invention. The dialysis regimen was the same in both groups (3 times a week for 4.5 hours), and hemodialysis sessions were carried out according to standard methods. 6 months after the start of the study, a “wash-out” period was prescribed, during which both groups received hemodialysis therapy using a standard solution. Further, the groups changed places, the patients receiving the sessions using the HDA according to the invention remained on standard hemodialysis, the control group began to receive the sessions using the solutions according to the invention, this stage of the study lasted 6 months.

According to the results of medical tests of the GDR according to the invention, the following effects from their use were established.

GDRs containing a mixture of acids have several advantages over standard bicarbonate hemodialysis.

Partial replacement of acetic acid with succinic acid for the first time allowed the hemodialysis procedure, aimed at removing toxins from the body, to become metabolic.

Succinic acid accelerates the turnover of the dicarboxylic part of the Krebs cycle, increasing the energy supply of the cell, increasing tissue oxygen consumption and improving tissue respiration.

First of all, it should be noted that the cardioprotective effect helps to stabilize angina pectoris, reduce the frequency and duration of periods of myocardial ischemia, and antiarrhythmic action.

In patients with chronic renal failure, the level of glutamyl transpeptidase (GGTP) is increased, which is exacerbated by concomitant liver diseases, chronic hepatitis, and cardiovascular failure (Table 18).

Table 18 Indicators, units measuring Control N = 90 Test group N = 90 Statistical Significance (ANCOVA) GGTP (E / l) 46.6 ± 5.1 25.9 ± 4.6 0.002

The established fact of a decrease in the level of GGTP in blood plasma in patients receiving a hemodialysis procedure with GDR containing a mixture of organic acids (succinic, citric) with inorganic (hydrochloric) acid is of great clinical significance, since it has been shown that the level of GGTP activity in plasma is directly related to risk of developing cardiovascular complications. A decrease in GGTP level can be attributed both to the action of succinate, since succinate stimulates the metabolic function of the liver with a simultaneous increase in the resistance of hepatocyte membranes to oxidative stress, and with a decrease in the load on the liver with acetate.

An extremely important result of the use of a dialysis solution containing a mixture of acids is the phosphate-lowering effect. Hyperphosphatemia is associated with high mortality in hemodialysis patients. Violations of phosphorus-calcium metabolism of one degree or another are present in all patients with chronic kidney disease. In the process of succinate metabolism, there is an active consumption of inorganic phosphate. Succinyl CoA synthetase, one of the key enzymes of succinate metabolism, has the ability to non-covalently bind a phosphate ion, which leads to an increase in the activity of this enzyme and, in turn, creates the conditions for an increase in the consumption of phosphate ion in mitochondria. A decrease in the level of phosphates is also facilitated by a decrease in the body's load with acetate, since the hyperphosphatemic effect of high doses of acetate during acetate hemodialysis is well known. The increase in the efficiency of phosphate removal is facilitated by the addition of citric acid to the GDR, which has an anticoagulant effect due to the binding of calcium at the level of the dialyzer membrane. This leads to an increase in the permeability of the membrane and an increase in the transfer of other molecules through the membrane of the dialyzer, in particular the succinic anion of succinic acid. The effectiveness of dialysis is increased. Succinate in the composition of the dialysis solution reduces the degree of inhibition of oxidative processes in the Krebs cycle, increasing intracellular accumulation of macroergic compounds, which can stimulate an increase in body weight and physical activity of patients. Succinate has an insulinotropic effect, being a metabolic mediator of the synthesis of proinsulin induced by glucose. The quality of life of patients is one of the most important criteria for the effectiveness of treatment. The effect of succinate can explain the decrease in the manifestations of hypoxic encephalopathy. Also, the mechanism of action of succinate can be associated with the participation of succinic acid in the synthesis of gamma-aminobutyric acid, one of the most important mediators of the nervous system.

The indicator of physical functioning and the total indicator of physical health are independent predictors of the survival of hemodialysis patients. The data obtained indicate positive changes in the quality of life of patients, which was manifested in the improvement of physical and role-based physical functioning; patients were less concerned about various restrictions, chest pain, joint pain, headaches, itching, cramps decreased, sleep was improved, and patients' ability to cope with physical activity improved significantly. The quality of social interaction has improved.

Introduction to the GDR of citric acid increased the effectiveness of hemodialysis, because due to the binding of calcium ions, thrombosis of the dialyzer capillaries was prevented, the efficiency of using succinic acid increased. In a shorter period, the patient's quality of life indicators improved

Thus, the use of GDR containing a mixture of organic and inorganic acids, compared with the use of bicarbonate hemodialysis with acetic acid in patients with chronic hemodialysis, leads to positive changes in a number of laboratory parameters, improving the physical condition of patients, their well-being and quality of life.

Claims (35)

1. A concentrated acid component for the preparation of a hemodialysis solution, including sodium chloride, calcium chloride, magnesium chloride, potassium chloride, succinic acid and acetic acid, characterized in that the amount of these components is calculated to obtain 1 liter of solution in purified water for hemodialysis, is, g:
sodium chloride NaCl 204.7-215.0 calcium chloride CaCl ₂ * 2H ₂ O 6.2-9.0 magnesium chloride MgCl ₂ * 6H ₂ O 3.56-7.12 potassium chloride KCl 5.22-10.44 acetic acid C ₂ H ₄ O ₂ 0.021-6.28 succinic acid C ₄ H ₆ O ₄ 0.02-6.2 2. The concentrated acid component according to claim 1, characterized in that it further comprises citric acid C ₆ H ₈ O ₇ in an amount of from 0.022 to 7.3 g. 3. The concentrated acid component according to any one of claims 1, 2, characterized in that it further comprises hydrochloric acid HCl in an amount of from 0.012 to 3.8 g. 4. The concentrated acid component according to any one of claims 1, 2, characterized in that it further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 76.0 g. 5. The concentrated acid component according to claim 3, characterized in that it further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 76.0 g. 6. The concentrated acid component according to any one of claims 1, 2, characterized in that the total amount of all acids is 105 meq. 7. The concentrated acid component according to claim 3, characterized in that the total amount of all acids is 105 meq. 8. A concentrated solution of the acid component to obtain a hemodialysis solution, including sodium chloride, calcium chloride, magnesium chloride, potassium chloride, acetic acid, succinic acid in dissociated form in the following amount, meq / l:
sodium ions Na ⁺ 3500.0-3675.0 calcium ions Ca ²⁺ 84.0-122.5 magnesium ions Mg ²⁺ 35.0-70.0 potassium ions K ⁺ 5.22-140.0 chlorine ions Cl ^- 3689.0-3937.5 acetate ions C ₂ H ₃ O ^2- 0.35-104.65 succinate ions

0.35-104.65 9. The concentrated solution of the acid component of claim 8, additionally containing citric acid in dissociated form, where citrate ions

present in an amount of 0.35 to 104.3 meq / l. 10. The concentrated solution of the acid component according to any one of claims 8, 9, further comprising hydrochloric acid in dissociated form, in which the content of chloride ions Cl ^- is from 0.35 to 104.3 meq / L. 11. The concentrated solution of the acid component according to any one of claims 8, 9, further containing glucose C ₆ H ₁₂ O ₆ in an amount of not more than 420 mmol / L. 12. The concentrated solution of the acid component of claim 10, additionally containing glucose C ₆ H ₁₂ O ₆ in an amount of not more than 420 mmol / L. 13. The concentrated solution of the acid component according to any one of paragraphs.9, 10, in which the total amount of all acids is 105 meq / L. 14. The concentrated solution of the acid component of claim 10, in which the total amount of all acids is 105 meq / l 15. A hemodialysis solution comprising a concentrated acid component according to any one of claims 1 to 7 or a concentrated solution of an acid component according to any one of claims 8 to 14, water purified for hemodialysis and a bicarbonate component. 16. The hemodialysis solution according to clause 15, having the following composition, meq / l:

sodium ions Na ⁺ 135.0-140.0 calcium ions Ca ²⁺ 2.4-3.5 magnesium ions Mg ²⁺ 1.0-2.0 potassium ions K ⁺ 2.0-4.0 chlorine ions Cl ^- 105.4-112.5 acetate ions

0.01-2.99 succinate ions

0.01-2.99 bicarbonate ions

27.0-40.0 17. Hemodialysis solution according to any one of paragraphs.15, 16, further containing citrate ions

in an amount of from 0.01 to 2.98 meq / l.
18 Hemodialysis solution according to any one of paragraphs.15, 16, further containing chloride Cl ions ^- in an amount of from 0.01 to 2.98 meq / l. 19. The hemodialysis solution according to claim 17, further comprising chloride Cl ions ^- in an amount of from 0.01 to 2.98 meq / l. 20. The hemodialysis solution according to any one of claims 15, 16, 19, further comprising glucose C ₆ H ₁₂ O ₆ in an amount of not more than 12.0 mmol / L. 21. The hemodialysis solution of claim 18, further comprising glucose C ₆ H ₁₂ O ₆ in an amount of not more than 12.0 mmol / L. 22. Hemodialysis solution according to clause 15, having the following composition, meq / l:
sodium ions Na ⁺ 138.0 calcium ions Ca ²⁺ 3,5 magnesium ions Mg ²⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions

0.3 succinate ions

0.7 chlorine ions (from hydrochloric acid) 1,5 citrate ions 0.5 bicarbonate ions

32,0 23. Hemodialysis solution according to clause 15, having the following composition, meq / l:
sodium ions Na ₊ 138.0 calcium ions Ca ²⁺ 3,5 magnesium ions Mg ²⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions

0.3 succinate ions

0.8 chlorine ions (from hydrochloric acid) 1.4 citrate ions 0.5 bicarbonate ions

32,0 24. Hemodialysis solution according to clause 15, having the following composition, meq / l:
sodium ions Na ⁺ 138.0 calcium ions Ca ²⁺ 3,5 magnesium ions Mg ²⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions

0.2 succinate ions

1,0 chlorine ions (from hydrochloric acid) 1,5 citrate ions 0.3 bicarbonate ions

32,0 25. Hemodialysis solution according to clause 15, having the following composition, meq / l:
sodium ions Na ⁺ 138.0 calcium ions Ca ²⁺ 3,5 magnesium ions Mg ²⁺ 1.00 potassium ions K ⁺ 2.0 chlorine ions Cl ^- 109.5 acetate ions

0.1 succinate ions

0.7 chlorine ions (from hydrochloric acid) 1,2 citrate ions 0.7 bicarbonate ions

32,0 26. Hemodialysis solution according to any one of paragraphs.22-25, further comprising glucose in an amount of 5.5 mmol / L. 27. A method of producing a hemodialysis solution according to any one of claims 15 to 26, comprising supplying a concentrated acid component according to any one of claims 1 to 7 or a concentrated solution of an acid component according to any one of claims 8 to 14 to a hemodialysis apparatus, dilution thereof purified water for hemodialysis and mixing with the bicarbonate component. 28. The method according to item 27, where the obtained hemodialysis solution has the following composition, meq / l:
sodium ions Na + 135.0-140.0 calcium ions Ca ²⁺ 2.4-3.5 magnesium ions Mg ²⁺ 1.0-2.0 potassium ions K ⁺ 2.0-4.0 chlorine ions Cl ^- 105.4-112.5 acetate ions

0.01-2.99 succinate ions

0.01-2.99 bicarbonate ions

27.0-40.0 29. A kit for producing a concentrated acid component according to any one of claims 1 to 7 or a solution of a concentrated acid component according to any one of claims 8 to 14, including sodium chloride, calcium chloride, magnesium chloride, potassium chloride, succinic acid in the form of dry reagents and acetic acid in the form of a liquid reagent, characterized in that the amount of these components, in order to obtain 1 liter of solution in purified water for hemodialysis, is, g:
sodium chloride NaCl 204.7-215.0 calcium chloride CaCl ₂ * 2H ₂ O 6.2-9.0 magnesium chloride MgCl ₂ * 6H ₂ O 3.56-7.12 potassium chloride KCl 5.22-10.44 acetic acid C ₂ H ₄ O ₂ 0.021-6.28 succinic acid C ₄ H ₆ O ₄ 0.02-6.2 30. The kit according to clause 29, characterized in that it further comprises citric acid C ₆ H ₈ O ₇ in an amount of from 0.022 to 7.3 g. 31. The kit according to claim 30, containing citric acid in the form of a dry reagent. 32. Set according to any one of paragraphs.29, 30, 31, characterized in that it further comprises hydrochloric acid HCl in an amount of from 0.012 to 3.8 g. 33. The kit according to p, containing hydrochloric acid in the form of a liquid reagent. 34. The kit according to any one of paragraphs.29, 30, 31, characterized in that it further comprises glucose With ₆ H ₁₂ About ₆ in an amount of not more than 76.0 g / L. 35. Set according to any one of paragraphs.32, 33, characterized in that it further comprises glucose C ₆ H ₁₂ O ₆ in an amount of not more than 76.0 g. 36. The kit according to any one of paragraphs.29, 30, 31, 33 in which the dry reagents may be in the form of a mixture and / or in the form of a set of individual components.