WO2011092551A1

WO2011092551A1 - Antimicrobial composition

Info

Publication number: WO2011092551A1
Application number: PCT/IB2010/051613
Authority: WO
Inventors: Анатолий Альбертович Кузьмин; Николаевич БОРОВКОАлександр
Original assignee: Kuzmin Anatolii Albertovich; Borovko Oleksandr Mykolajovych
Priority date: 2010-01-29
Filing date: 2010-04-14
Publication date: 2011-08-04
Also published as: EA019978B1; UA94177C2; EA201170368A1

Abstract

The invention relates to veterinary medicine, in particular to preparations intended for the prophylaxis and treatment of diseases caused by Gram-positive and Gram-negative microorganisms, the simplest, for example pathogens of salmonellosis, colibacteriosis, pasteurellosis, mycoplasmosis and other diseases. The antimicrobial composition contains trimethoprim and/or at least one fluoroquinolone or at least one pharmaceutically acceptable salt of fluoroquinolone, at least one organic acid, auxiliary substances and a pharmaceutically acceptable solvent, wherein said composition additionally comprises at least one macrolide antibiotic or at least one pharmaceutically acceptable salt of a macrolide antibiotic. Therefore, the claimed invention constitutes an antimicrobial composition which, owing to the qualitative and quantitive structure thereof, is highly effective therapeutically when treating combined infectious diseases. The use of the composition according to the present invention also ensures highly effective and simple treatment of patients being subjected to the treatment, and is economically expedient and safe on account of a reduction in the probability of the components of the composition having side effects.

Description

Title of Invention: ANTI-MICROBIAL COMPOSITION

Technical field

Field of Invention

[1] The invention relates to veterinary medicine, in particular to

drugs intended for the prevention and treatment of diseases caused by gram-positive and gram-negative

microorganisms, protozoa, for example, pathogens of salmonellosis, colibacteriosis, pasteurellosis, mycoplasmosis and other diseases.

Background art

BACKGROUND OF THE INVENTION

[2] It is widely known that in veterinary medicine antibiotics, sulfonamides, nitrofuran preparations are used to treat various diseases. However, prolonged use of antibiotics leads to the emergence of strains of microorganisms resistant to these drugs, which requires an increase in doses and constant updating of the means of combating pathogens of infections. In addition, prolonged use of antibiotics has a significant negative effect on the body of subjects undergoing treatment. In the practice of veterinary medicine, antibacterial compositions containing sulfonamides and

trimethoprim, the advantage of which for a long time was considered the synergism of the above components. However, recently studies show that synergism in such compositions is mainly a laboratory phenomenon and does not have any significant significance for the clinical effectiveness of such drugs [Bramfitt W., Hamilton-Miller J.M.T. Limitations of and indications for the use of co-trimoxazole. J.

Chemother., 1994, 6, 3-11]. Trimethoprim may slow the development of resistance to sulfonamides. However, an increase in sensitivity to sulfonamides can also be explained by a decrease in selective pressure due to a decrease in their use. The sulfanilamide component of such compositions in most clinical situations is not valuable, due to the high microflora resistance to

sulfonamides. In addition, it is the sulfonamide component that represents the risk of severe adverse reactions and drug interactions.

[3] Fluoroquinolones are also widely used. First-generation fluoroquinolones had low activity against gram-positive bacteria. In addition, with reusable them

microorganisms become resistant to

fluoroquinolones. Further scientific developments led to the synthesis of fluoroquinolones of the second, third and fourth generations and the development of new medicinal compositions. Modern fluoroquinolones, even in small concentrations, have high antibacterial activity against gram-positive and gram-negative bacteria, as well as against mycoplasmas. The disadvantages of fluoroquinolones include the risk of developing a number of side effects, such as a reaction from the gastrointestinal tract, central nervous system, photosensitivity. When taking fluoroquinolones, it is often necessary to simultaneously take immunostimulants, since these drugs have a systemic effect on the body. Also, some microorganisms have high resistance to fluoroquinolones. Therefore, the trend is the use of fluoroquinolones in conjunction with other types of antibiotics, in particular with macrolides.

[4] Macrolides are bacteriostatic antibiotics

a wide spectrum of action, which at high concentrations can have a bactericidal effect. Their chemical structure is based on the macrocyclic lactone ring. Depending on the number of carbon atoms in this ring, macrolides are divided into 3 groups: 14-, 15- and

16-membered. A nitrogen atom is included in the ring of 15-membered macrolides, and therefore they are more often (and more correctly) called azalides.

[5] The prototype of the macrolide antibiotic group is erythromycin, which has been used in clinical practice since the early 1950s. The drug is most active in vitro against gram-positive cocci (streptococcus and staphylococcus) and gram-positive rods, including Bacillus anthracis, Corynebacterium diphtheriae, Clostridium spp. and Listeria monocytogenes. In addition, the antibiotic is active against gram-negative cocci (Neisseria spp.), Gram-negative bacilli, including strains of Legionella pneumophila, Pasteurella multocida, Brucella spp., And intracellular microorganisms (Mycoplasma pneumoniae, Ureaplasma urealyticum, Chlamyppia trama rdiappia tramisdiachiappia tramisdiachiappia trama. . The spectrum of action of erythromycin also includes Actinomyces spp., Treponema spp., Entamoeba histolytica, Borrelia burgdorferi, Haemophilus influenzae, Mycobacterium kansasii, M. scrofulaceum and some bacteroids (including Bacteroides fragilis). Viruses, fungi, bacteria of the Enterobacteriaceae family, Pseudomonas spp. and Acinetobacter spp. possess natural resistance to erythromycin.

[6] The spectrum of action of other macrolides is generally similar to that

erythromycin, but has some features for each macrolide. New macrolides are superior to erythromycin in action on some protozoa (Toxoplasma gondii), spirochetes (B. burgdorferi), and atypical intracellular mycobacteria M. avium, which often cause opportunistic infections in AIDS patients.

[7] It can also be said that macrolides are considered as potential immunomodulators. One of the main mechanisms

the immunomodulatory effect of antimicrobial agents is a modification of the structure and factors of virulence of microorganisms.

Macrolides, like other antibiotics that suppress protein synthesis in bacterial cells, cause changes in the cell membrane of microbes, leading to increased phagocytosis. This is due to a decrease in the expression on the surface of bacterial cells of certain proteins with antifagocytic functions.

[8] In general, the effectiveness of the treatment of infectious diseases

antimicrobial drugs depends on the correct choice of the drug, taking into account the sensitivity of the pathogen to it, the choice of the optimal dose, the frequency and duration of its use, which is possible after making an accurate diagnosis, isolating the pathogen and determining its sensitivity. A preliminary diagnosis is made on the basis of epizootological, clinical and

pathological data, and the final one - according to the results of bacteriological, serological and other necessary research methods. To isolate the pathogen and determine it

antimicrobial sensitivity required

for a long time, because treatment of animals often begins on the basis of a preliminary diagnosis.

[9] In livestock production, and in particular in poultry farming, mixed infections are a serious problem. For example, infection of chickens with mycoplasmas very often involves infection of animals with other pathogens. Mycoplasmosis disease is characterized by the fact that the subject is a carrier of the pathogen for a long time. The manifestation of clinical signs contributes to a decrease in the overall resistance of the body against a background of productive and biological stress factors.

Acute mycoplasmoses often develop against the background of other, more dangerous infections, when the immune system of the host organism is weakened or unable to adequately perceive mycoplasmas as foreign objects. Mycoplasma itself, which is extremely important, can increase the sensitivity of birds to viral infections, such as Newcastle disease, as well as to live vaccines, which is caused by damage to the local defense mechanism and immunosuppressive effect. Mycoplasmas also facilitate access of birds to bacterial infections, and especially to E. coli. The fact that mycoplasma as an infection is complicated

colibacteriosis, confirm the results of serological studies. Therefore, the use of mixed infections of drugs directed against only one pathogen does not lead to

a positive result because other or other species

microorganisms remain in the body of the animal and exert their pathogenic effect. Therefore, it is advisable to use drugs with a broad antimicrobial spectrum of activity, complex drugs. Thus, the trend is the creation of an antimicrobial composition that would combine the aforementioned drugs, which would overcome some of their shortcomings and provide a composition with a high therapeutic effect.

] The closest analogue of the claimed invention is

antimicrobial composition described in the patent of Ukraine for utility model Ν ° 46335, which contains trimethoprim, and / or at least one fluoroquinolone, or at least one pharmaceutically

an acceptable fluoroquinolone salt, at least one organic acid, excipients, and a pharmaceutically acceptable solvent.

] The disadvantages of the described composition can be attributed to

its low effectiveness in the treatment of mixed infections, since the effect directed at only one pathogen does not lead to a positive result, since another or other types

microorganisms remain in the body of the subject undergoing treatment and exert their pathogenic effect.

Disclosure of invention

The essence of the invention

] The basis of the invention the task of creating an antimicrobial

composition, which due to its qualitative and quantitative composition will provide high therapeutic efficacy in the treatment of mixed infectious diseases, the use of which will ensure the ease of treatment of subjects undergoing treatment, and will also be economically feasible and safe by reducing the likelihood of side effects of the components of the composition.

[13] The problem is solved in that an antimicrobial composition is developed containing trimethoprim and / or at least one fluoroquinolone or at least one pharmaceutically acceptable salt of fluoroquinolone, at least one organic acid,

excipients and a pharmaceutically acceptable solvent, wherein the composition further comprises at least one macrolide antibiotic or at least one pharmaceutically acceptable salt of the macrolide antibiotic.

[14] A similar composition provides a therapeutic and

preventative efficacy and spectrum expansion

antimicrobial action of the drug due to the formation

complex drug, the use of which allows to provide a positive therapeutic effect in the treatment of mixed infections, and the resulting antimicrobial composition is safer for subjects undergoing treatment, by reducing the likelihood of side effects of the components of the composition.

[15] An embodiment of the invention is possible in which the antimicrobial composition has the following ratio of components, mass. %:

[16] Macrolide antibiotic or its pharmaceutically acceptable salt

0.1-50

[17] Trimethoprim 0.1-30

[18] Organic acid 0, 1 -90

[19] Excipients 0.1-20

[20] A pharmaceutically acceptable solvent is the rest.

[21] The combination of macrolide antibiotic or its pharmaceutically

an acceptable salt with trimethoprim can provide the creation of a comprehensive drug with a wide spectrum of antimicrobial activity, and the use of the claimed composition is economically feasible and safe by reducing the likelihood of side effects of the components of the composition. The specified quantitative content of the components of the composition is sufficient to provide a therapeutically effective effect in a condition that is prevented or treated, as well as for the implementation

preventive exposure to prevent possible diseases in birds and mammals. Also, the indicated quantitative content of the elements is optimal from the point of view of the safety of receiving the antimicrobial composition and avoids possible side effects during treatment with the inventive composition.

The therapeutically effective amount of the components of the composition will vary depending on the specific condition being treated, the physical condition of the subjects being treated, the severity of the condition to be treated / prevented, the duration of treatment, the nature of the simultaneous therapy, the specific compound or composition used, the particular pharmaceutically acceptable adjuvant used and similar factors.

[22] An embodiment of the invention is also possible in which

the antimicrobial composition has the following ratio of components, mass. %:

[23] Macrolide antibiotic or its pharmaceutically acceptable salt 0.1-50 [24] Fluoroquinolone or its pharmaceutically acceptable salt 0.1-40

[25] Organic acid 0, 1 -90

[26] Excipients 0.1-20

[27] A pharmaceutically acceptable solvent is the rest.

[28] The combination of macrolide antibiotic or its pharmaceutically

acceptable salt with fluoroquinolone or a pharmaceutically acceptable salt thereof allows for the creation of a comprehensive drug with a wide spectrum of antimicrobial activity, and the use of the claimed composition is economically

expedient and safe by reducing the likelihood of side effects of the components of the composition. The indicated quantitative content of the components of the composition is sufficient to provide

a therapeutically effective effect in a condition that

prevent or treat, as well as for the implementation of preventive measures to prevent a possible disease in birds and mammals. Also, the indicated quantitative content of the elements is optimal from the point of view of reception safety

antimicrobial composition and avoids possible side effects during treatment using the claimed composition. A therapeutically effective amount of the components of the composition will vary depending on the specific condition being treated, the physical condition of the subjects being treated, the severity of the condition to be treated / prevented, the duration of treatment, the nature of concurrent therapy, the specific compound or composition used, the particular pharmaceutical used

an acceptable adjuvant and similar factors.

[29] Another embodiment of the invention is an antimicrobial composition, which has the following ratio of components, mass. :

[30] Macrolide antibiotic or a pharmaceutically acceptable salt thereof 0.1-50

[31] Trimethoprim 0.1-30

[32] Fluoroquinolone or a pharmaceutically acceptable salt thereof 0.1-40

[33] Organic acid 0.1-90

[34] Excipients 0.1-20

[35] A pharmaceutically acceptable solvent is the rest.

[36] The combination of macrolide antibiotic or its pharmaceutically

acceptable salt with trimethoprim and fluoroquinolone or its

a pharmaceutically acceptable salt can provide the creation of a comprehensive drug with a wide spectrum of antimicrobial activity, and the use of the inventive composition is economically feasible and safe by reducing the likelihood of side effects of the components of the composition. The specified quantitative content of the components of the composition is sufficient to provide a therapeutically effective effect in a condition that is prevented or treated, as well as for the implementation

preventive exposure to prevent possible

diseases in birds and mammals. Also, the indicated quantitative content of the elements is optimal from the point of view of the safety of receiving the antimicrobial composition and avoids possible side effects during treatment with the inventive composition.

[37] Introduction to the composition of organic acid allows you to provide

complete dissolution of the sparingly soluble components of the composition of macrolides, fluoroquinolones and trimethoprim, which in turn allows for high therapeutic efficacy of the composition and a convenient soluble dosage form for oral administration. [38] It is advisable to such an embodiment of the invention in which the macrolide antibiotic or its pharmaceutically acceptable salt is selected from the group consisting of: erythromycin, spiramycin,

midecamycin, oleandomycin, roxithromycin, josamycin, troleandomycin, clarithromycin, azithromycin, myocamycin, roquitamycin, dirithromycin, flurithromycin, telithromycin, tylosin, tilmicycin, kitazamycin, gamma thromycin. Macrolide antibiotics are a large group of antibiotics (natural and semi-synthetic), the basis of the chemical structure of which is a macrocyclic lactone ring with one or more carbohydrate residues. Depending on the number of carbon atoms in the ring, macrolides are divided into 14-membered (erythromycin, clarithromycin, roxithromycin), 15-membered (azithromycin) and 16-membered (josamycin, midecamycin, spiramycin). By spectrum and degree

representatives of this group are close to antibacterial activity, with the exception of new semi-synthetic macrolides (azithromycin and clarithromycin), which are more active against many intracellular bacteria, some pathogens of dangerous infections (brucella, rickettsia), gram-positive and gram-negative non-spore-forming anaerobes, and other mechanisms are protein synthesis inhibitors. As a rule, macrolides have a bacteriostatic effect, but under certain conditions - with a change in the pH of the medium, a decrease in the density of the inoculum, and high concentrations in the medium - they can act bactericidal. Modern semi-synthetic

macrolides are characterized by a wide spectrum of action: they are active against most gram-positive microorganisms, many gram-negative bacteria, “atypical” intracellular pathogens of respiratory infections; the spectrum of their action also includes atypical mycobacteria, pathogens of a number of dangerous infectious diseases (rickettsia, brucella, borrelia, etc.) and some protozoa. They surpass natural macrolides not only in breadth of spectrum and degree of antibacterial activity, but also in bactericidal effect on many pathogens. Also, the use of macrolide antibiotics is due to their ability to accumulate and for a long time to linger in

immunocompetent cells after completion of therapy, their high safety during use, as well as high economic

the effectiveness of their implementation.

[39] It is advisable to such an implementation of the invention, in which

fluoroquinolone or a pharmaceutically acceptable salt thereof is selected from the group which contains: ofloxacin, ciprofloxacin, pefloxacin, enoxacin, temafloxacin, norfloxacin, lomefloxacin, fleroxacin,

sparfloxacin, rufloxacin, grefafloxacin, levofloxacin,

trovafloxacin, moxifloxacin, hemifloxacin, gatifloxacin, prulifloxacin, pazufloxacin, garenoxacin, enrofloxacin,

danofloxacin, mabrofloxacin, difloxacin, orbifloxacin,

ibafloxacin, sitafloxacin, clinafloxacin. Fluoroquinolones are characterized by a wide spectrum of antimicrobial activity, including staphylococci, high bactericidal activity and good pharmacokinetics, which allows them to be used to treat infections of various localization.

Fluoroquinolones, put into practice since the mid-90s (III-IV

generation), are characterized by higher activity against gram-positive bacteria (primarily pneumococci),

intracellular pathogens, anaerobes (IV generation), as well as even more optimized pharmacokinetics. The presence of a number of drugs

dosage forms for intravenous administration and oral administration in combination with high bioavailability allows for step therapy, which with comparable clinical efficacy

significantly cheaper than parenteral.

[40] Fluoroquinolones, in contrast to non-fluorinated quinolones, have a large distribution volume, create high concentrations in organs and tissues, and penetrate the cells. The degree of metabolism depends on the physicochemical properties of the drug: pefloxacin is most biotransformed, lomefloxacin, ofloxacin is the least active,

levofloxacin. With feces, 3-4% to 15-28% of the dose taken is excreted.

The half-life of various fluoroquinolones ranges from 3-4 hours (norfloxacin) to 12-14 hours (pefloxacin, moxifloxacin) and even up to 18-20 hours (sparfloxacin).

[41] the Introduction of fluoroquinolone or its pharmaceutically acceptable salt in

composition in an amount of 0.1-40 mass. % provides the most optimal and balanced effect, because it allows you to dose

an antibacterial composition, depending on the amount of water or feed consumed by the subject being treated.

[42] It is also advisable to use as another

the active substance trimethoprim, which is a competitive inhibitor of dihydrofolate reductase and disrupts one of the stages of the synthesis of nucleic acids - the formation of tetrahydrofolate from dihydrofolate. Trimethoprim has a pronounced antibacterial activity against many gram-positive and gram-negative microbes. The introduction of trimethoprim in the composition in an amount of 0.1-30 mass. % provides the most optimal and balanced effect, because it allows you to dose the antimicrobial composition depending on the amount consumed by the subject undergoing treatment, the amount of water or feed.

[43] It is also advisable to such an implementation of the claimed invention, in which the organic acid is selected from the group which includes: ascorbic, formic, acetic, valerian, kapron, enanthic, malic, tartaric, lactic, oxalic, succinic,

propionic, citric, malonic, glutaric acids. Introduction to the composition of an organic acid in an amount of 0.1-90 mass. % allows for the complete dissolution of sparingly soluble components

compositions of fluoroquinolones and trimethoprim, which in turn allows for high therapeutic efficacy in the treatment

mixed infectious diseases in subjects exposed to an antimicrobial composition.

[44] It is preferable to use stabilizers and / or preservatives and / or antioxidants as adjuvants.

The inclusion of excipients allows to ensure the receipt of the selected dosage form of the composition, safe storage and subsequent use of the composition in veterinary medicine.

[45] Using the inventive composition, it is possible to treat home and

ornamental birds, mammals, in particular cattle and small cattle, pigs, horses from infectious diseases caused by gram-positive and gram-negative microorganisms, in particular: Salmonella spp., Enterobacter spp., Klebsiella spp., Proteus spp., Shigella spp., Citrobacter spp., M. Morgami, M. galisepticum, Vibrio spp., Haemophilus spp., Neisseria spp., Pseudomonas spp., Listeria spp., Pasteurella spp., Legionella spp., Staphylococcus spp., E. coli, Serratia spp. ., St. epidermidis, St. aureus, S. piogenes, Providencia spp.

Examples

[46] Options for the implementation of the antimicrobial composition according to this

The invention is illustrated by the following examples.

[47] Example 1

[48] Antimicrobial composition in the following ratio

components, wt. :

[49] Tilmicosin phosphate 0, 1 [50] Enrofloxacin 0.1

[51] Trimethoprim 0, 1

[52] Acetic acid 0.1

[53] Benzyl alcohol 0, 1

[54] Water is the rest.

[55] The indicated quantitative content of the components of the composition is minimal and in this case, it is necessary to use a sufficiently large amount of the drug. However, even with such a quantitative content of components, the composition has sufficient

therapeutic efficacy in the treatment of mixed infections, and is also easy to use and safe by reducing the likelihood of side effects of the components of the composition. When the content of the components below the specified number, it is not possible to achieve the required

therapeutic effect.

Example 2

Antimicrobial composition in the following ratio

components, wt. :

Tylosin phosphate 10

Norfloxacin 10

Trimethoprim 5

Acetic acid 10

Benzyl alcohol 1

Water is the rest.

The specified quantitative content of the components of the composition is one of the most preferred and with such a quantitative

the content of the components, the composition has high therapeutic efficacy in the treatment of mixed infections, and is also easy to use and safe by reducing the likelihood of side effects of the components of the composition.

Example 3

Antimicrobial composition in the following ratio

components, wt.%:

Tilmicosin Phosphate 40

Trimethoprim 5

Lactic Acid 40

Benzyl alcohol 0, 1

Water is the rest.

The indicated quantitative content of tilmicosin phosphate is maximum, since tilmicosin phosphate is poorly soluble in concentrations of more than 40%. With such a quantitative content of components, the composition has a high therapeutic

effective in mixed infections, and is also easy to use and safe by reducing the likelihood of side effects of the components of the composition.

[73] The minimum inhibitory concentration of the claimed antimicrobial composition and the reference drug (10% enrofloxacin solution) was determined by the method of micro-dilutions in liquid nutrient media.

[74] Table 1.

[75] Minimum Inhibitory Antimicrobial Concentration

composition and comparison drug, mcg / ml (n = 5)

[Table 1]

[Table]

[76] The method of micro-dilutions in liquid nutrient media was used to determine the minimum bactericidal concentration of the claimed antimicrobial composition and the reference drug (10% enrofloxacin solution).

[77] table 2

[78] Minimum bactericidal antimicrobial concentration

composition and comparison drug, mcg / ml (n = 5)

[Table 2]

[Table]

From the tables Tables 1 and 2 shows that the claimed antimicrobial the composition is significantly superior to the comparison drug in

antibacterial action, which indicates a synergistic effect.

[80] Treatment with the claimed antimicrobial composition

carried out as follows.

[81] The antimicrobial composition may be used to treat

mixed infectious diseases of poultry and mammals of any age, for example, for the treatment of mixed infection

mycoplasma + E. coli. The inventive composition is added to drinking water or feed in an optimal concentration of 1: 1000 once a day for 5 days. However, the duration of treatment may vary depending on the condition of the exposed subjects.

antimicrobial composition.

[82] Study of the therapeutic efficacy of an antimicrobial composition

carried out on chickens.

[83] As a comparison drug used a drug containing 10%

enrofloxacin. For studies used chickens no more than 4 months old. The criterion for the selection of animals for the experiment was the presence of signs of colibacteriosis and respiratory mycoplasmosis: general depression, lack of appetite, profuse diarrhea and severe thirst, signs of damage to the respiratory system. The diagnosis has been confirmed.

bacteriological studies.

[84] The antimicrobial composition and the reference preparation were given with water at a dose of 1 ml per 1 liter of drinking water for 5 days.

[85] The clinical definition of efficacy included mortality, the number of non-recovering subjects undergoing treatment, and the number of recovering.

[86] The results of the studies are shown in Table 3. Mortality in the group receiving the comparison drug was higher (7% versus 2%) than in the group receiving the claimed antimicrobial composition.

[87] Table 3

[88] The results of a study of therapeutic efficacy

Antimicrobial composition and drug comparison on chickens [Table 3]

[Table]

Thus, the claimed invention is a

antimicrobial composition, which due to its qualitative and quantitative composition has a high therapeutic

effective in the treatment of mixed infectious diseases. Also, the use of the composition according to this invention provides greater efficiency, ease of treatment of subjects undergoing treatment, is economically feasible and safe by reducing the likelihood of side effects of the components of the composition.

Claims

1. An antimicrobial composition that contains trimethoprim and / or at least one fluoroquinolone, or at least one pharmaceutically acceptable salt of fluoroquinolone, at least one organic acid, excipients, and a pharmaceutically acceptable solvent, characterized in which further comprises at least one macrolide antibiotic, or at least one pharmaceutically acceptable salt of the macrolide antibiotic.

2. The antimicrobial composition according to claim 1, characterized in that it has the following ratio of components, mass. %: Macrolide antibiotic or its pharmaceutically

acceptable salt 0.1-50

Trimethoprim 0.1-30

Organic acid 0.1-90

Excipients 0.1-20

A pharmaceutically acceptable solvent is the rest.

3. The antimicrobial composition according to claim 1, characterized in that it has the following ratio of components, mass. %: Macrolide antibiotic or its pharmaceutically

acceptable salt 0.1-50

Fluoroquinolone or a pharmaceutically acceptable salt thereof 0.1-40 Organic acid 0.1-90

Excipients 0.1-20

A pharmaceutically acceptable solvent is the rest.

4. The antimicrobial composition according to claim 1, characterized in that it has the following ratio of components, mass. :

Macrolide antibiotic or its pharmaceutically

acceptable salt 0.1-50

Trimethoprim 0.1-30

Excipients 0.1-20

A pharmaceutically acceptable solvent is the rest.

5. The antimicrobial composition according to claim 1, characterized in that the macrolide antibiotic or its pharmaceutically an acceptable salt selected from the group that contains:

erythrimycin, (erythromycin) spiramycin, midecamycin, oleandomycin, roxithromycin, josamycin, troleandomycin, clarithromycin, azithromycin, myocamycin, roquitamycin, dirithromycin, flurithromycin, tilomycin, tylithromycin, tylithromycin, tylomycin,

[Claim 6] 6. The antimicrobial composition according to claim 1, characterized in that fluoroquinolone or a pharmaceutically acceptable salt thereof is selected from the group consisting of: ofloxacin,

ciprofloxacin, pefloxacin, enoxacin, temafloxacin, norfloxacin, lomefloxacin, fleroxacin, sparfloxacin, ruploxacin, grefafloxacin, levofloxacin,

trovafloxacin, moxifloxacin, hemifloxacin,

gatifloxacin, prulifloxacin, pazufloxacin,

garenoxacin, enrofloxacin, danofloxacin,

mabrofloxacin, difloxacin, orbifloxacin, ibafloxacin, sitafloxacin, clinafloxacin.

[Claim 7] 7. The antimicrobial composition according to claim 1, characterized in that the organic acid is selected from the group which includes: ascorbic, formic, acetic,

valerianic, caproic, enanthic, malic, tartaric, lactic, oxalic, succinic, propionic, citric, malonic, glutaric acids.

[Claim 8] 8. The antimicrobial composition according to claim 1, characterized in that stabilizers and / or preservatives and / or antioxidants are used as auxiliary substances.

[Claim 9] 9. The antimicrobial composition according to claim 1, characterized in that it is used to treat infections caused by

gram-positive and gram-negative

microorganisms, protozoa.