Composition, containing crystallisation-inhibiting substances

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a composition, adapted for intravenous introduction, intended for the treatment or prevention of pathological processes of crystallisation or calcification in a person, subjected to dialysis. The composition contains inositol phosphate and/or its pharmaceutically acceptable salt, with a dose of inositol phosphate and/or its salt constituting from 1 nmol/kg to 0.1 mil/kg. The invention also relates to a combined method of treatment, including the intravenous introduction of the said composition of the dialysis liquid simultaneously.

EFFECT: method is intended for the treatment or prevention of pathological processes, associated with an impairment of the regulation of physiologically adequate levels of inositol phosphate in blood plasma of the person, subjected to dialysis.

10 cl, 4 dwg, 1 tbl, 9 ex

 

The invention relates to compositions containing inositolfosfatov and/or bisphosphonates, and to use this composition to prevent loss of biological substances values in patients undergoing dialysis, and maintain physiological levels of these substances for the regulation of physiological and/or pathological processes, these substances are inhibitors of pathological crystallization.

The LEVEL of TECHNOLOGY

Acute renal dysfunction consists of a rapid decrease of excretory kidney function. Patients suffering from this pathological condition, treat with the use of various therapeutic alternatives, which include hemodialysis and peritoneal dialysis.

Due to lack of excretory functions in the course of renal failure, the accumulation of end products of metabolism. In cases when the kidneys are unable to perform their function, to save the lives of patients had to undergo a process of dialysis or kidney transplant.

Dialysis is one of the alternatives that is used as a treatment of this breach, and includes the use of semi-permeable membrane that separates the blood from the other liquid, called dialysis fluid or dialysis fluid.

When the dialysis and the use of the artificial kidney, the most important part, which is dialysator. The dialysator consists of a compartment for blood and the other compartment of the dialysis fluid, the fluids are always circulating in opposite directions in order to make the most used diffusion instead of the gradient of the concentration of the solution. Both compartments are separated by a semi-permeable membrane, which mainly can be 4 different types:

- cellulose membrane (Cuprofan): it is used most widely. It consists of chains of glucose rings with many free hydroxyl groups;

- substituted cellulose membranes: they are obtained through chemical bonding between the large number of free hydroxide radicals and acetate. Also referred to as cellulose acetate;

- cellulosecontaining membrane: modification by adding a synthetic material, such as diethylaminoethyl upon receipt of hemophan;

- synthetic membranes: they do not contain cellulose and are more biocompatible than cellulose membranes. Varieties of this type of membranes include polyacrylonitrile, polysulfone, polyamide or poly (methyl methacrylate).

In peritoneal dialysis, a scheme similar to that in hemodialysis, although used a semi-permeable membrane is a peritoneal mesotheli that pok which indicates the inner surface of the abdominal cavity and the organs within it. Thus, the dialysis fluid is introduced into the abdominal cavity, while the Bay for the blood is the lumen of the capillaries that irrigate the peritoneal mesotheli.

The composition of the dialysis fluid is such that through the process of diffusion has become possible to eliminate waste substances from the blood, and, in addition, it becomes possible to regulate the amount of water and the concentration of electrolytes in it, due to the controlled composition of ions, such as ions of sodium, potassium, chloride ion, magnesium ion or calcium.

This fluid also has a high concentration of glucose (which makes possible the achievement of isotonic with plasma osmolality) and buffered acetate or bicarbonate buffer.

However, the blood contains natural substances that are not present in the dialysis liquid, but which, nevertheless, have biological significance. These substances are subjected to a removal process in the implementation process of dialysis using a semipermeable membrane (Van der, Kaau J., Van Haastert, P. J. M., Analytical Biochemistry 1999; 225: 183-185). Moreover, this removal process can remove up to 100% of the substance, the percentage that can be modified depending on the ionic strength of the environment.

DETAILED description of the INVENTION

There is a need to maintain effective physio is logicheskih concentrations of certain substances, which may contribute to the regulation of the processes of physiological and/or pathological crystallization and calcification.

In particular, it is necessary to improve the composition of the dialysis fluid in order after the process of dialysis, which these patients have had to undergo, the concentrations of some biological substances in the serum were not significantly reduced, or for the introduction of certain substances into dialyzing fluid to plasma concentration after dialysis was sufficient. Alternatively, the desired modification of the concentration of these substances during the process of dialysis, their plasma concentration can again be governed by intravenous injection of the composition. The levels of these substances may be regulated by an intravenous injection before, during or after the process of dialysis, which exposed patients.

Therefore, the present invention relates to the introduction of substances having biological significance, for example, in the composition of the dialysis liquid and/or intravenous compositions and to their use to prevent the loss of these substances from the blood, maintain sufficient levels in plasma or raise plasma levels to physiologically sufficient quantities.

The value of these substances and similar compounds for patients undergoing dialysis, is special is important, if we take into account that renal failure leads to situations hyperphosphatemia, which increases the supersaturation of calcium phosphate in the urea and, consequently, can cause pathological processes of cardiovascular calcification.

The present invention is the introduction of substances having activity as inhibitors of crystallization in the composition of the dialysis liquid and/or intravenous compositions. In particular, the aim is the introduction of inositolfosfatov, more specifically, phytate, and/or bisphosphonates in the composition of dialysis fluid, and inositolfosfatov, phytate among them, intravenous composition.

In particular, the present invention relates to compositions of dialysis fluid and intravenous compositions which contain substances with activity as inhibitors of crystallization. More specifically, these substances are inositolfosfatov, preferably phytate and/or bisphosphonates.

Bisphosphonates are synthetic compounds that are resistant to enzymatic hydrolysis, phosphate, and therefore exogenous their intake by mouth is more effective than pyrophosphate. Although their use as medicines is focused on the treatment processes of bone resorption, they also have properties which AMI inhibitors of crystallization of calcium salts. On the other hand, phytate or monothioglycerol is a molecule with outstanding properties as an inhibitor of crystallization of calcium salts, as it has 6 phosphate groups and, therefore, a high affinity against divalent ions such as calcium. Thus, the described preventive properties regarding the development of pathological calificaci, such as renal lithiasis or cardiovascular calcification.

The introduction of substances in the composition of dialysis fluid can prevent their loss from the blood, to maintain adequate plasma levels or to increase their plasma levels to physiologically sufficient quantities. Alternatively, setting the modification of the concentration of these substances during the process of dialysis, the concentration of plasma can again be governed by intravenous injection of the composition before, during or after dialysis.

In the present invention, "crystallization inhibitor" means a substance that is able to prevent, limit or reduce the crystallization at any stage, education, whether the centers of crystallization, crystal growth or aggregation.

In the present invention, "dialysis fluid or dialysis fluid" means an electrolyte solution similar to blood plasma, which does not contain from Botanik substances, which accumulate in the body in case of renal failure. This solution is used in the process of dialysis to reduce the accumulation of end products of metabolism, regulation of plasma volume and the regulation of the concentration of electrolytes in the blood.

Professionals in this field know that one of the key elements of the process of dialysis dialysis is a membrane that is part of the artificial kidney, in the case of hemodialysis and peritoneal mesotheli in the case of peritoneal dialysis. In both cases, the pore size of the membrane prevents the loss of macromolecules, such as proteins, during the process of dialysis, but allows the exchange of electrolytes and substances with low molecular weight. Thus, appropriate amounts of ions, for example, sodium, potassium, chloride, magnesium, or calcium introduced into the dialysis fluid used to maintain sufficient levels in plasma.

However, there are no descriptions enable inositolfosfatov and/or bisphosphonates in these compositions dialysis fluid, which would have prevented the decrease in plasma concentration during dialysis (due to the concentration gradient between blood and dialysis fluid, which allows diffusion and, therefore, the excretion of these substances) or to maintain/increase their concentrate the radio plasma after dialysis (figures 1-4). Basically, they are substances with a low molecular weight, which therefore pass through the pores of the semipermeable membranes used in dialysis. Moreover, as an alternative to the above method, the modification of the plasma concentration of inositolfosfatov patients can be corrected by intravenous injection of the composition.

These substances can be of natural origin, as in the case of phytate and other inositolfosfatov, but synthetic substances that exhibit a similar function, as in the case of bisphosphonates, may also be introduced into the composition.

Thus, the first aspect of the present invention relates to compositions containing substances that inhibit crystallization selected from the group consisting of insidiosum, a bisphosphonate, pharmaceutically acceptable salt, or any combination thereof, for use in receiving dialysis fluid.

Inositols may contain from 1 to 6 phosphate groups (Inositol mono-, di-, tri-, Tetra-, Penta - and hexaphosphate). In a preferred embodiment, the substance, inhibiting crystallization, is inositols containing from 1 to 6 phosphate groups, more preferably, inositoltrifosfata (also called phytic acid or phytate) and, more preferably, myoinositol apostate.

In a preferred embodiment, the substance, inhibiting crystallization, is a bisphosphonate selected from the group consisting of etidronate acid, alendronate acid, risedronate acid, zoledronic acid, tiludronate, pamidronovu acid, clodronate acid, ibandronate acid, salt, or any combination thereof. The preferred implementation of the dialysis liquid or intravenous compositions of the present invention optionally contains other compounds such as, for example, without limitation, pyrophosphate and/or any of its pharmaceutically acceptable salts.

The concentration of these substances in the dialysis liquid and/or intravenous composition will depend on several factors such as the composition of the dialysis fluid, time of dialysis, the severity of renal dysfunction and so on. In the present invention were obtained stable composition of dialysis fluid, in which the number of intitolata and/or bisphosphonates is in the range from 0.1 μm to 0.1 M. Preferably, the concentration of intitolata and/or bisphosphonates is in the range from 0.1 μm to 10 mm; more preferably, from 0.1 μm to 1 mm.

An example of the composition of dialysis fluid for peritoneal dialysis and hemodialysis), to which this type of substances could be added, would consist of glucose, soda is I, potassium, chlorine, calcium, magnesium, buffer (mainly, without limitation, bicarbonate or acetate), and so on. On the other hand, high concentration of glucose makes possible the regulation of osmolality, so that she was isotonic plasma. In addition, dextrose, lactate, heparin, antibiotics or additional components that perform a specific function, can be introduced into the plasma.

Another aspect of the present invention relates to a dialysis fluid containing substances that inhibit crystallization selected from the group consisting of inositols, a bisphosphonate, pharmaceutically acceptable salt, or any combination of them, and using them to maintain, improve or prevent a decrease in plasma concentrations of the indicated inhibitory substances.

The composition according to the present invention can be included in the composition of the dialysis fluid or composition adapted for intravenous administration.

Therefore, another aspect of the present invention relates to compositions containing inositols and/or any of its salts in a form adapted for intravenous administration, for use in the treatment or prevention of pathological processes associated with dysregulation of physiologically adequate levels of these substances in the blood plasma. Treatment or prevention is in violation of the regulation of conduct by maintaining or increasing the levels of these substances in the plasma of the patient. Pathological processes associated with dysregulation of physiologically adequate levels of these substances in the blood plasma are very different in nature and may include, without limitation, to any pathology associated with impaired metabolism of calcium, such as renal lithiasis, cardiovascular calcification, calcification of the skin, osteoporosis or calcium gout. On the other hand, this is a violation or infringement of the regulation also applies to cancer, especially certain types of cancer, such as bowel cancer, bone or skin.

In the case of intravenous compositions were obtained stable compositions in which the number of input intitolata is in the range from 1 nmol/kg to 0.1 mol/kg (relative to body mass of the patient, who introduced this song). Preferably, the concentration of intitolata is in the range from 0.01 µmol/kg to 10 mmol/kg; more preferably, from 0.1 µmol/kg to 1 mmol/kg

The substance, inhibiting crystallization, preferably represents inositols containing from 1 to 6 phosphate groups, more preferably, inosilicates and, more preferably, monothioglycerol. This composition may further contain pyrophosphate.

Example IV composition contains Ino is italpasta and can optionally contain sodium, chlorine, buffer and/or other excipients, carriers and inhibiting substances, such as bisphosphonates or pyrophosphate.

In the present invention "intravenous" includes both injection or direct introduction, the introduction of the composition in the form of a bolus, in pure form or diluted, and intravenous infusion, in which the composition is injected through the venous channel by means of intravenous infusion.

On the other hand, another aspect of the present invention relates to a combined preparation that contains at least the composition of the present invention and dialysis fluid used separately, simultaneously or sequentially in the treatment or prevention regulation physiologically adequate levels of inhibitory substances, to maintain or increase these levels in the plasma of patients under dialysis.

In a preferred embodiment, the composition according to the invention, used in the combined preparation is in a form adapted for intravenous.

Throughout the text of the description and claims the word "contains" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For specialists in this field for other purposes, advantages and features of the present invention p the will are partly from the description and partly from the practical implementation of the present invention. The following examples and drawings are presented for purposes of illustration and are not intended to limit the scope of the present invention.

BRIEF DESCRIPTION of DRAWINGS

The Figure 1 shows that up to 40% of phytate in a sample of the artificial blood plasma during dialysis using a dialysis fluid without phytate is lost by excretion through 20 hours.

On Figure 2 it is shown that phytate in a sample of the artificial blood plasma during dialysis using a dialysis fluid with a concentration of phytate higher than in plasma, makes it possible to increase the plasma concentration over a 20-hour period.

The Figure 3 shows that up to 95.6% of the etidronate in a sample of the artificial blood plasma during dialysis using dialysis idxt without etidronate is lost by excretion through 20 hours.

The Figure 4 shows that etidronate in a sample of the artificial blood plasma during dialysis using a dialysis fluid with the concentration of etidronate higher than in plasma, makes it possible to increase the plasma concentration over a 20-hour period.

EXAMPLES

Below the present invention will be illustrated by studies conducted by the inventors, which shows the specificity and efficacy of the composition according to the invention, the input is in the form of my injections, intravenous infusion or dialysis fluid.

Example 1

Artificial plasma (the liquid with a composition similar to that of plasma) was obtained with 1.5 mm phytate, adjusting the ionic strength using 0.15 M NaCl. 25 ml of this solution deliberately for 20 hours against 1 l of the volume of 0.15 M NaCl solution without phytate (model dialysis fluid), the pH of both solutions was brought to 7.4 using bicarbonate buffer.

5-ml aliquots of dialysis fluid were collected at times 0, 1, 3, 6 and 20 hours and determined the amount of phytate in each of them. Moreover, the concentration of phytate in the artificial plasma was determined at time 0 and 20 hours.

The concentration of phytate in the artificial plasma after 20 hours of dialysis was 40% lower than the initial concentration. The Figure 1 shows that during the process of dialysis is the removal of phytate, increasing the amount of phytate in the dialysis solution up to 40% of the original quantity in the artificial plasma is reached after a time period of 20 hours.

Example 2

Artificial plasma was obtained with 1.5 mm phytate, adjusting the ionic strength using 0.15 M NaCl. 25 ml of this solution deliberately for 20 hours against 1 l of the volume of 0.15 M NaCl solution with the same concentration of phytate in the plasma. the pH of both solutions was brought to 7.4 using bicarbonate buffer.

5-ml aliquots dialysis liquid is collected at time 0, 1,3, 6 and 20 hours and determined the amount of phytate in each of them. Moreover, the concentration of phytate in the artificial plasma was determined at time 0 and 20 hours.

During the process of dialysis has not been fluctuations in the concentration of phytate neither in plasma nor in dialysis fluid; therefore, the introduction of phytate into dialyzing fluid prevents the loss of this substance in the blood.

Example 3

Artificial plasma was obtained with 300 μm phytate, adjusting the ionic strength using 0.15 M NaCl. 25 ml of this solution deliberately for 20 hours against 1 l of the volume of 0.15 M NaCl solution with a concentration of phytate 5 times higher than the concentration in plasma. the pH of both solutions was brought to 7.4 using bicarbonate buffer.

5-ml aliquots of dialysis fluid were collected at times 0, 1, 3, 6 and 20 hours and determined the amount of phytate in each of them. Moreover, the concentration of phytate in the artificial plasma was determined at time 0 and 20 hours.

The results are shown in figure 2. It is observed that during the process of dialysis up to 0.75% of the phytate from the dialysis fluid is included in the artificial plasma, therefore, in consideration of the ratio of the source volumes and concentrations, the concentration of phytate in the artificial plasma increased by 140%; therefore, it is possible to restore the normal levels of phytate by entering it into a dialysis the second liquid.

Example 4

Artificial plasma was obtained with 5 mm of etidronate, adjusting the ionic strength using 0.15 M NaCl. 25 ml of this solution deliberately for 20 hours against 1 l of the volume of 0.15 M NaCl solution without etidronate (model dialysis fluid). the pH of both solutions was brought to 7.4 using bicarbonate buffer.

5-ml aliquots of dialysis fluid were collected at times 0, 1, 3, 6 and 20 hours and the number of etidronate was determined in each of them. Moreover, the concentration of etidronate in artificial plasma was determined at time 0 and 20 hours.

The concentration of etidronate in artificial plasma after 20 hours of dialysis was 95.6% lower than the original concentration. On figure 3 you can see that during the process of dialysis is the removal of etidronate, increasing the number of etidronate in the dialysis solution to achieve 95,6% of the original quantity in the artificial plasma after a period of time of 20 hours.

Example 5

Artificial plasma was obtained with 5 mm of etidronate, adjusting the ionic strength using 0.15 M NaCl. 25 ml of this solution deliberately for 20 hours against 1 l of the volume of 0.15 M NaCl solution with the same concentration of etidronate, and that in the plasma. the pH of both solutions was brought to 7.4 using bicarbonate buffer.

5-ml aliquots of dialysis fluid were collected at times 0, 1, 3, 6 and 20 hours and the number is the creation of etidronate was determined in each of them. Moreover, the concentration of etidronate in artificial plasma was determined at time 0 and 20 hours.

During the process of dialysis has not been fluctuations in the concentration of etidronate neither in plasma nor in dialysis fluid; therefore, the introduction of etidronate into dialyzing fluid prevents the loss of this substance in the blood.

Example 6

Artificial plasma was obtained with 1 mm of etidronate, adjusting the ionic strength using 0.15 M NaCl. 25 ml of this solution deliberately for 20 hours against 1 l of the volume of 0.15 M NaCl solution with a concentration of etidronate, 5 times greater than that in plasma. the pH of both solutions was brought to 7.4 using bicarbonate buffer.

5-ml aliquots of dialysis fluid were collected at times 0, 1, 3, 6 and 20 hours and the number of etidronate was determined in each of them. Moreover, the concentration of etidronate in artificial plasma was determined at time 0 and 20 hours.

The results are shown in figure 4. You can see that during the process of dialysis up to 1.65% of the etidronate of the dialysis fluid is included in the artificial plasma, therefore, in consideration of the ratio of the source volumes and concentrations, the concentration of etidronate in artificial plasma increased by 330%; therefore, it is possible to increase the levels of etidronate in plasma by introducing it into the dialysis fluid.

Example 7

The composition of dialysis fluid for haemodialysis and peritoneal dialysis), to which add inositols and/or bisphosphonates:

ConnectionComposition 1Composition 2
Inositols and/or a bisphosphonate0.1 ám - 0.1 M
Glucose200 mg/DL250 mg/DL
Sodium136 mEq/l146 mEq/l
Potassium0 mEq/l3 mEq/l
Chlorine96 mEq/l115 mEq/l
Calcium2.5 mEq/l3.25 mEq/l
Magnesium0.5 mEq/l1.5 mEq/l
The buffer35 mEq/l40 mEq/l

High glucose concentration makes it possible to regulate osmollnosti, so that she was isotonic plasmas is. Moreover, in the plasma can be entered dextrose, heparin, lactate, antibiotics and additional connections that perform a specific function.

Example 8

Added to the compositions, intended for intravenous administration to patients undergoing various medical procedures (as treatment by injection or intravenous infusion and hemodialysis or the peritoneal dialysis), which added inositolfosfatov, including phytate. The concentration of intitolata set as a function of the volume of intravenous to obtain the quantities specified in the table.

ConnectionComposition 1Composition 2
Inositols1 nmol/kg/day to 0.1 mol/kg/day M
Sodium-146 mEq/l
Chlorine-115 mEq/l

Moreover, can be introduced incremental connections that perform a specific function.

Example 9

6 male Wistar rats weighing approximately 250 g were acclimatized for 7 days in room LM is now (T=1±1°C and relative humidity =60±5%) with 12:12-hour svetotonovye cycles. The rats were kept in Plexiglas cages, one animal per cage, and fed and given to drink ad libitum.

After the adaptation period the animals were randomly divided into two groups of 3 rats in each control group (diet without phytate, thereby mimicking postdialysis physiological state) and the test group, which received 3 intravenous doses of 0.61 mmol/kg (400 mg/kg), divided 12-hour periods of time. After the last introduction of 24-hour urine samples were collected for determination of phytate and subsequently animals were anestesiology and collected blood samples.

The procedures used in this experiment, carried out in accordance with Directive 86/609/EEC regarding the protection of animals used for experimental and scientific purposes.

Excretion of phytate with urine at the end of the study was significantly lower in the control group (4,0+/-1,5 mcg) compared with the test group (72+/-10 μg). When comparing levels in the plasma, the value of 0.013+/-0,006 mg/l was obtained for the control group and 1.0+/-0,2 mg/l for the test group; therefore, for the first time it was shown that intravenous injection of the composition in terms of plasmapheresis inositolfosfatov able to adjust these insufficient levels, reaching much higher levels in plasma than can be achieved by oral administration, no matter how surprising is entrusted, even 24 hours after intravenous injection.

1. The composition is adapted for intravenous administration, for the treatment or prevention of pathological processes of crystallization and calcification in humans undergoing dialysis containing inositols and/or its pharmaceutically acceptable salt, in which the dose of intitolata and/or its pharmaceutically acceptable salt is from 1 nmol/kg to 0.1 mol/kg

2. Composition under item 1, in which the pathological processes of crystallization and calcification selected from renal lithiasis, cardiovascular calcification, calcification of the skin and calcium gout.

3. Composition according to any one of paragraphs.1 or 2, in which inositols contains from 1 to 6 phosphate groups.

4. The composition according to p. 3, in which inositols is inositoltrifosfata.

5. The composition according to p. 4, in which inositols is monothioglycerol.

6. Composition according to any one of paragraphs.1, 2, 4, and 5, in which the dose of intitolata and/or any of its pharmaceutically acceptable salts is from 0.01 µmol/kg to 10 mmol/kg

7. Composition according to any one of paragraphs.1, 2, 4, 5, which further comprises a pyrophosphate.

8. Composition according to any one of paragraphs.1, 2, 4, 5, where the treatment or prevention of disorders of the regulation of conduct by maintaining or increasing levels of intitolata and/or it is salt in the plasma of man, undergoing dialysis.

9. Combined method of treatment, which includes intravenous administration of compositions containing inositols or its pharmaceutically acceptable salt, and a dialysis fluid simultaneously for the treatment or prevention of pathological processes associated with dysregulation of physiologically adequate levels of intitolata and/or its salts in the blood plasma of a person undergoing dialysis.

10. Combined method of treatment for p. 9, in which the composition further comprises a bisphosphonate.



 

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3 ex

FIELD: medicine.

SUBSTANCE: invention relates to narcology, and can be used in treatment of patients with frost bites, who are in the state of alcoholic intoxication of different severity. For this purpose determined are: degree of frostbite, area of affection, degree of alcoholic intoxication, physiological needs of organism and pathological loss during a day. After that, volume of infusion therapy is calculated by formula: V=(CfsxS)+(CfxSVIT)+PN+PL, where: V is volume of infusion therapy, in ml; Cfs is coefficient of frost bite severity: 1.0 in case of I and II degree frost bites; 2.0 in case of III-IV severity degree frost bite; S is area of affected surface, in cm2; Ca is coefficient of alcoholic intoxication severity: 0.5 in case of mild degree, 0.75 in case of medium severity; 1.0 in case of severe degree; 1.5 - in case of alcoholic coma; SVIT is standardised volume of infusion therapy, in case of alcoholic intoxication equal 2500 ml per day: PN stands for physiological needs of organism for a day, in ml; PL stands for pathological loss within a day, in case of I and II degree frost bites constituting 500 ml; in case of III and IV degree frost bites constituting 1000 ml.

EFFECT: method ensures adequate and differentiated carrying out infusion therapy in said category of patients, taking into account degree of alcoholic intoxication, which contributes to prevention of "mutual aggravation" syndrome, minimisation of hemostasis and microcirculation, as well as prevention of encephalopathy of complex genesis, alcoholic psychosis, including cases after carrying out necrotomy and fasciotomy.

3 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to resuscitation and intensive therapy and can be used in treatment of hemorrhagic shock of I, II and II degree of severity. Method of hemorrhagic shock treatment. For this purpose, assessment of degree of hemorrhagic shock severity is carried out, and in case of hemorrhagic shock of 1 degree of severity in the programme of infusion therapy included are: crystalloid solution of isotopic sterofundin in dose 3000 ml per day and 4% colloidal solution of modified gelatin in volume 1000 ml per day, in case of hemorrhagic shock of II degree of severity - 1200 and 2500 ml respectively, in case of hemorrhagic shock of III degree of severity - 1200 and 3500 ml respectively.

EFFECT: method makes it possible to improve results of treating patients with hemorrhagic shock at pre-hospital and hospital stages due to reduction of risk of electrolyte and acid-alkaline disorders.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an antibacterial composition and is intended for the oral cavity care. The antibacterial composition contains an antibacterial system, including a 4-isopropyl-3-methylphenol (IPMP) source of zinc ions and alkali metal C8-18 alkylsulphate and a perorally acceptable carrier or an excipient. The composition Ph constitutes from 5.5 to 7.5.

EFFECT: application of the invention provides the antimicrobial activity.

9 cl, 4 dwg, 3 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and represents a local pharmaceutical composition for treating rosacea containing at least 0.02% berberine or a biologically equivalent berberine analogue, such as palmatine, and an ingredient specified in a group consisting of water, methanol, ethanol and dimethylsulphoxide, wherein berberine or the biologically equivalent berberine analogue represents the major pharmaceutically active ingredient.

EFFECT: invention provides extending the range of products for treating rosacea.

4 cl, 6 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: invention represents eye drops containing a pharmaceutically acceptable additive acid salt and methylethylpyridinole, taurine and a composition of group B vitamins.

EFFECT: creating the combined preparation for treating traumatic and dystrophic eye injuries causing no irritant action and possessing improved pharmacological properties.

5 cl, 6 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: what is declared is an infusion solution for filling the deficiency and meeting the physiological needs for water and basic electrolytes, which contains the following ingredients: sodium (Na+) - 27.72-28.28 mmole/l; fumarate(H2C4O42-) - 13.86-14.14 mmole/l; potassium (K+) - 18.61-18.99 mmole/l; calcium (Ca2+) - 3.56-3.64 mmole/l; magnesium (Mg2+) - 2.18-2.22 mmole/l; chlorine (Cl-) - 30.0-30.6 mmole/l; glucose (C6H12O6) - 189.1-192.9 mmole/l, water for injections.

EFFECT: solution contains the basic electrolyte concentration balanced for meeting the physiological needs; it is safe for the clinical application and can be used in diseases of various aetiology for patients of any age.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents an injectable form of 5α-androstane-3β,5,6β-triol containing a liquid injectable form, containing a solvent, or a solid injectable form containing at least one soluble additive with the above at least one soluble additive containing hydroxypropyl-β-cyclodextrine.

EFFECT: invention provides preparing the stable injectable form of 5α-androstane-3β,5,6β-triol.

10 cl, 7 ex, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to an injection medical composition for local application in treatment of haemorrhoid, which contains hydroxychloroquine. In particular, the composition contains hydroxychloroquine in a physiological solution for injection with a local anaesthetic and an antioxidant.

EFFECT: injection composition by the invention ensures strengthening of haemorrhoid tissue for blocking metabolism in the haemorrhoid tissue, and as a result -necrosis of the haemorrhoid tissue.

5 cl, 8 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: storage-stable pharmaceutical composition represents a liquid formulation containing bortezomib and a system of anhydrous solvents and applicable for injection. A primary ingredient of the system of anhydrous solvents is propylene glycol. Bortezomib is found in the concentration of at least 1 mg/ml. The pharmaceutical composition contains a total amount of aqueous buffer of 10 vol. % or more.

EFFECT: stable pharmaceutical composition according to invention maintains bortezomib degradation at the level of not less than 10 wt % when keeping the liquid formulation for at least three months in the ambient environment.

9 cl, 10 tbl

FIELD: medicine.

SUBSTANCE: invention represents an irrigation solution containing sodium chloride, mono- and dibasic sodium phosphate, glycosaminoglycans, glucose or its derivatives, water-soluble cellulose or its derivatives, neuraminic acid, an antihypertensive agent and water.

EFFECT: irrigation solution is balanced; it possesses the anti-inflammatory, anti-oedemic and antihypertensive properties.

3 ex

FIELD: medicine.

SUBSTANCE: viscoelastic solution for the posterior hyaloid contrast enhancement contains a colouring agent, methyl cellulose, hyaluronic acid, low polyvinyl pyrrolidone and injectable water. The colouring agent is presented by trypan blue and/or brilliant blue. The ingredients are used in the declared ratio.

EFFECT: lower toxic effect of the retina, improved intraoperative visualisation of cortical layers of the vitreous body.

3 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to veterinary science and aims at normalising metabolic processes, stimulating immune system and blocking mechanisms of infectious process with a risk of endogenous infection activation. A method for producing a combination immunometabolic preparation with anti-infectious activity involves dissolving succinic acid and levamisole in demineralised water with formalin added. According to the other aspect of the invention, the immunometabolic preparation additionally contains polyethylene glycol. The ingredients are used in the declared ratio.

EFFECT: using this group of inventions provides producing an injection form of the immunometabolic preparation with anti-infectious activity.

2 cl, 3 tbl

FIELD: medicine.

SUBSTANCE: invention represents an irrigation solution containing sodium chloride, mono- and dibasic sodium phosphate, glycosaminoglycans, glucose or its derivatives, water-soluble cellulose or its derivatives, neuraminic acid, an antihypertensive agent and water.

EFFECT: irrigation solution is balanced; it possesses the anti-inflammatory, anti-oedemic and antihypertensive properties.

3 ex

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