RU2480239C2 - Antibacterial agent - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology of bacteriophagues. An antibacterial agent contains a bacteriophage concentrate, any preserving agent, except for those related to quaternary ammonium derivatives, heavy metal derivatives, oxidising agents, bromine or iodine-containing, formaldehyde-releasing preserving agents, water, a gelling agent in the form of a non-ionic or anionic high-molecular compound, a non-ionic surfactant and a pH adjustor in the following ratio, wt %: bacteriophage concentrate of Appelman's lytic activity min. 10^-4 for each type of bacteriophague - 0.001-10.0; gelling agent - 0.05-15.0; surfactant - 0.001-2.0; preserving agent - 0.05-0.6; pH adjustor to 6.0-8.0; water up to 100.0.

EFFECT: extended range of products containing bacteriophages as a basic active ingredient, provided biological stability and activity of bacteriophages in the composition of the product; the composition possess a low risk of toxicity and side effects, provides storage stability and efficacy within the wide range of temperatures.

11 cl, 15 ex

Description

The invention relates to the field of biotechnology of bacteriophages and can be used in the manufacture of finished products of cosmetic pharmaceutical, household, veterinary use, as well as in the field of hygiene, disinfection and to protect agricultural, processing and food products from microbial spoilage.

A known method of disinfection and a device that aerosol distributes at least one bacteriophage (US 2005244383, 2005). In this case, only one type of packaging is described and the method of use is a container from which the agent containing the bacteriophage is scattered. Those. There is a restriction on the method of use, storage conditions and methods of use.

Known antibacterial composition comprising a surfactant and an effective amount of one or more bacteriophages (EP 414304, 1991).

It is also known a tool in the form of liniment for the treatment of diseases (RF patent No. 2104015, 1998). The product contains a bacteriophage, a solution of chinosol, albumin, anhydrous lanolin and vegetable oil.

The closest previously known means is a gel dosage form of a medical immunobiological preparation containing bacteriophages and preservatives (RF patent No. 2156133, 2000).

The disadvantages of these inventions are:

- lack of consideration of a number of features of the biological nature of bacteriophages as viruses (the life cycle of which is aimed at carrying out attacks, infection of bacteria and their own reproduction at their expense);

- the lack of consideration of physico-chemical criteria, the observance of which stabilizes bacteriophages during storage in the finished form of the product and provides high efficiency in the manifestation of antibacterial properties.

For example, the use of only surface-active substances (surfactants) or only gelling agents to stabilize the suspension of bacteriophages in most cases is not enough to ensure product stability during long-term storage (or with a sharp change in storage temperature) and significantly limits the arsenal of options for finished forms and methods of practical use of products .

Other disadvantages of the known funds are:

- the absence or irrational use of high molecular weight substances that allows you to adjust the viscosity and colloidal stability of the particles of bacteriophages and improve the titer and antibacterial activity of bacteriophages;

- the absence of preservatives that stabilize the indicators of microbiological purity of products during production, storage and use, because a high level of product contamination in the absence of a preservative (by microorganisms of any nature, kind, type) can also cause a decrease in the specific lytic, antibacterial activity of bacteriophages;

- the requirements for surfactants are not indicated: what nature is of ionicity, what value of HLB (hydrophilic-lipophilic balance) should have. So, surfactants with a low HLB value and / or anionic and / or cationogenic nature can cause rapid sedimentation, inactivation and destruction of bacteriophages. The proposed high concentrations of surfactants in the range of 5% and above can also be the cause of lysis and inactivation of bacteriophages. Amphoteric surfactants (for example, lecithin) also have certain limitations on the use of bacteriophages in the composition. The charges of amphoteric surfactants vary depending on pH, and during the transition from acidic to alkaline pH, the type of surfactant changes from cationic through zwitterionic to anionic. The charged group in the structure of the surfactant negatively affects the composition with bacteriophages, because it can enhance aggregation and / or reduce the adsorption capacity of bacteriophages when interacting with bacteria. A change in the charge of an amphoteric surfactant depending on pH necessarily affects its properties such as foaming and wetting abilities, solubilizing effect. Therefore, when the pH and ionic activity of the medium change during the manufacture, storage or use, such surfactants can also act as lytic and inactivating agents with respect to bacteriophages. Only at the isoelectric point (narrow pH range), the physicochemical properties of such surfactants are similar to the properties of nonionic surfactants, that is, they can be used as part of a composition with bacteriophages;

- the criteria are not defined according to which the gelling agents can act only as stabilizers of bacteriophages and be absolutely inert to their biological activity. For example, gelling agents such as chitosan, hyaluronic acid, carrageenan, gelatin, pectin, albumin are able to form positively charged groups (centers) in the aquatic environment under certain conditions, which can act as blockers and reversible or irreversible inactivators of the lytic activity of bacteriophages. This is often the reason that during long-term storage and in practical use, when environmental conditions change, bacteriophages can dramatically reduce their activity and the actual antibacterial effect. Polyethylene glycol as the only thickener for producing viscous gels requires the use of such concentrations when the high density of glycol groups begins to exhibit antimicrobial, including "Antibacteriophageal" properties. Such products (using non-standardized and / or cationic gelling agents) have an irreproducible result that can be difficult to predict in the range from satisfactory to complete lack of effect;

- the role of reactive oxygen species in the energy supply of the processes of motion and other vital functions of bacteriophages has not been taken into account. With a deficiency of ROS (in vivo), bacteriophages can lose activity, lytic ability;

- the optimal titer (concentration) of bacteriophages (expressed by Appelman in the limiting dilution with lytic activity or by Grace in the number of negative colonies) is not clearly indicated necessary and sufficient for the implementation of the antibacterial effect, taking into account the different ways of using and the means of entry of funds with bacteriophages into the body;

- the use of a number of plant extracts and essential oils, also due to antimicrobial and, in particular, antiviral activity, can significantly reduce the specific activity of bacteriophages.

The task of the invention is to create a new composition using bacteriophages as the main active principle (taken in a certain amount for the manifestation of a biological result, taking into account the method of using the composition). The composition takes into account the physicochemical parameters of the environment (basics) that are optimal for the bacteriophage to display the desired effect, and the composition has manufacturability (simplicity and reproducibility in the manufacture of finished forms), versatility (the ability to include various combinations of bacteriophages and ensuring their stability), improving storage results in terms of bacteriophage activity, the possibility of obtaining ready-made forms with a wide range of organoleptic characteristics, convenience and diversity I have ways to apply. The composition contains bacteriophages and the basis of the product, which stabilizes bacteriophages and provides the necessary physical, chemical and consumer characteristics of the product.

Studies on the stability and activity of bacteriophages in various forms of agents (using different combinations of excipients) and at different temperature conditions have shown that the optimal prescription basis for ensuring colloidal stability and uniform distribution in bacteriophages is a combination containing simultaneously surfactant and a gelling agent (high molecular weight compound, polymer), as well as a pH regulator and preservative.

The antibacterial agent according to the invention contains a bacteriophage concentrate, preservative and water, and is characterized in that it additionally contains a gelling agent in the form of a nonionic or anionic high molecular weight compound, a nonionic surfactant and a pH regulator in the following ratio, wt.%:

bacteriophage concentrate with lytic activity Appelman not lower than 10 ^-4 for each type of bacteriophage 0.001-10.0 gelling agent 0.1-15.0 Surfactant 0.001-2.0 preservative 0.05-0.5 pH adjuster to ensure pH 6.0-8.0 water up to 100.0

Particular cases of the invention will be disclosed below with specific examples of the implementation of funds.

Characterization of the qualitative composition of bacteriophages in the composition

As a bacteriophage (as part of the composition described in the invention), any combination of any bacteriophage lysogenic (active) against any microorganisms (bacteria) that pose a threat to human or animal (or plant) health or cause food spoilage can be used. The combination of bacteriophages can be presented both in the form of a bacteriophage of one species (strain, subspecies, etc.), and in the form of a set of different bacteriophages active against one species or kind of microorganisms, or in the form of various combinations of bacteriophages active against different (several) species and genera of microorganisms (bacteria).

The combination of bacteriophages (even in relation to the same pathology, the same type of bacteria) cannot be constant and requires periodic improvement, refinement, and adaptation. This is due to the fact that microorganisms and their associations that cause certain pathological processes, or are sources of domestic, seasonal, infectious, nosocomial infections, undergo constant changes. Pathogenic microorganisms are constantly changing, have a large set of mechanisms to protect themselves, to hide from natural and therapeutic agents (antibiotics, sulfonamides, etc.).

In addition, the high selectivity (selectivity) of the lytic effect of bacteriophages in relation to a particular strain of the microorganism can be attributed both to a positive characteristic of phagotherapy (since the risk of side effects and dysbacteriosis is reduced), and to a disadvantage (since a natural change in the properties of a bacterial strain lead to a decrease and even loss of bacteriophage activity).

In the present invention, the criteria and requirements for the composition are formulated (to ensure storage stability and effectiveness when used), and the requirements for bacteriophages, methods for their isolation, purification, concentration and their biological characteristics are not regulated (not limited), and are ensuring the necessary and sufficient concentration, and in constant refinement and improvement of the set of bacteriophages itself, by isolating new bacteriophages active against detected bacteria, and their inclusion in the combination of bacteriophages.

Characterization of the quantitative content of bacteriophages in the composition

Especially significant changes in the anatomy, physiology, biochemistry, pathogenicity, virulence of bacteria (pathogenic and conditionally pathogenic) occur when these bacteria overcome specific concentration indicators (population density), which can be expressed in CFU (colony forming unit when controlling in vitro) per cm ³ during the study biological fluids or in CFU / cm ² when examining surfaces or in CFU / m ³ when examining gaseous media.

When favorable conditions are created for the propagation of pathogenic and conditionally pathogenic bacteria (for example, when immunity is weakened, when stresses are depleted, the body is depleted, while all the nutritional needs of bacteria are met, and the bacteria concentration of competing normal microflora is reduced (with dysbiosis), their concentration increases. At the same time, between microorganisms of one species or several varieties, when they reach sufficient concentrations, biochemical signaling systems (communication interactions) are included among themselves within the framework of a microcolony or association, which is the cause of the genetic, pathogenetic rearrangement of microorganisms. This effect is called “quorum sensig” - a sense of quorum.

The effect of bacteria quorum is a variant of their social, collective behavior (quorum sensing) of microorganisms. The response of microorganisms to changes in environmental conditions in a biofilm is significantly different from the reaction of each individual species in a monoculture. Such an organization ensures its physiological and functional stability and, therefore, is the key to competitive survival in the ecological niche.

The advantage of a collective response also has a negative side: such a community is difficult to manage from the outside (for example, to treat diseases of polymicrobial origin, when the sensitivity to antibiotics of microorganisms associated in a biofilm does not correspond to that defined in laboratory tests on clinical isolates of pure bacterial cultures). Collective protection of biofilms (or associative infections) practically negates the possibility of correcting dysbiosis with probiotics, bacteriocins and reduces the effectiveness of antibiotic therapy and disinfection.

The “quorum sensing” intercellular signaling system of potentially pathogenic microorganisms monitors the cell density of the bacterial population and is responsible for controlling the production of many extracellular pathogenicity factors, which ensures that bacteria overcome the defenses of the macroorganism during infection.

It is known that the manifestation of pathogenic properties in many conditionally pathogenic, low-virulent bacteria (causative agents of opportunistic infections) is formed when they overcome the concentration (population density) from 10 ⁴ CFU / cm ³ to 10 ⁵ CFU / cm ³ and higher. This population density includes in the bacterium a mechanism for enhancing virulence and manifestation of its pathogenic potential.

However, even with a constant presence or ingestion in a concentration below this, these bacteria may not show their negative effect on the macroorganism. In this case, the mechanisms of immune defense are activated, bacteria protect the normal microflora (natural microbiocenosis), i.e., a healthy body. In addition, low concentrations of these bacteria can contribute to the formation and strengthening of various forms of macroorganism immunity.

In this case, the use of bacteriophages can just act as a natural limiter of the population density of bacteria, pathogens of various infections.

An essential criterion for the realization of their bacteriolytic activity, obtaining a quick effect and reducing the risk of masking and collective protection of bacteria is the sufficient concentration and viability of bacteriophages at the place of their application or in the place where the pathogen is localized.

Although bacteriophages have the ability to increase their numbers due to parasitization and reproduction in bacteria, their initial low numbers at the attack site leave the bacteria with temporary, biochemical and genetic reserves to form resistance or to hide from the attack.

Concentrations of bacteriophages with lytic activity of 10 ^-4 according to Appelman (limiting dilution of a suspension of the bacteriophage that can cause lysis of a culture of sensitive bacteria in a liquid nutrient medium) is sufficient to ensure a rapid decrease in the number (limiting population density) and turning off the quorum sensing signaling system in bacteria to show antibacterial and / or therapeutic result to reduce the risk of bacterial resistance or the possibility of changing their characteristics (unrecognizable by their bacteriophages) or for the appearance of persistent forms of bacteria in a macroorganism (for example, disguised, protected and waiting in the form of various encapsulated forms).

When forming methodological approaches in determining the optimal (minimum sufficient) concentration of bacteriophages, the following criteria were used and taken into account:

1. The titer (concentration) of bacteriophages in the composition should be comparable with the population density (quorum sensing) of the target bacterial species (ie, not lower than 10 ^-4 by Appelman or 10 ^4- by Grace).

2. Experiments of controlling CFU of infection pathogens or other negative microflora (for example, CFU contamination of food products, air, surfaces), observed during the development of a negative (infection, infection) process.

3. Accounting for the inactivation of bacteriophages during storage, use, when it enters the processed object or in the body (when reaching the localization site of the pathogen).

As a result of research, experiments, calculations and analysis of publications in this invention, any combination of bacteriophages at a concentration of not less than 10 ^-4 according to Appelman of one type of bacteriophage is used as bacteriophages.

Moreover, depending on the method of application, the following bacteriophage concentrations are optimal:

- funds applied to the skin - 10 ^-4 -10 ^-6 according to Appelman;

- food processing means - 10 ^-4 -10 ^-6 Appelman;

- prolonged forms (applications) of external use not less than 10 ^-7 according to Appelman;

- funds for wounds and burns - 10 ^-7 -10 ^-9 according to Appelman;

- funds for internal use (oral) - 10 ^-7 -10 ^-9 according to Appelman;

- funds for rectal, vaginal administration - 10 ^-6 -10 ^-8 according to Appelman;

- for aerosol treatment of air and surfaces - 10 ^-4 -10 ^-6 according to Appelman;

- for aerosol treatment of plants - 10 ^-4 -10 ^-6 according to Appelman

- for concentrated semi-finished products containing bacteriophages for introduction into the composition of the product under production conditions of at least 10 ^-7 according to Appelman.

When studying the influence of various components and physico-chemical factors of the basics on the stability of bacteriophages during storage and on the manifestation of their lytic activity, the following were used:

1. Bacteriophages isolated from natural sources by known and generally accepted methods.

2. A collection of bacteria isolated from natural sources and obtained from the All-Russian Collection of Industrial Microorganisms.

3. Instruments, reagents and standard methods for physico-chemical and microbiological studies: Brookfield viscometer, pH meter, instruments for measuring electrical conductivity and redox potential, etc.

As a result, the following criteria were established, the requirements for the composition of the composition basis.

Water is used with the necessary degree of purification - purified or distilled, either for injection or deionized.

Non-ionic surfactant (nPAS) or nPAS complex with an HLB index (hydrophilic-lipophilic balance) of 9 and higher in a concentration of from 0.001 to 2 wt.%, Preferably 0.01-0.5%.

Options:

1. Esters of polyethylene glycol with organic acids (or alcohols) of synthetic or natural origin, including those derived from vegetable oils (hydrogenated or non-hydrogenated).

Synonym: ethoxylated fatty acids, alcohols, natural and hydrogenated vegetable oils. Preferred PEG 40 hydrogenated castor oil, Laureth-9.

2. Esters of polyethylene glycol with dimethicone (a copolymer of silicone and glycol), more preferably PEG-12 dimethicone.

3. Esters of polyhydric alcohols or carbohydrates with organic acids, preferably Tween-80 (synonyms: polysorbate-80, polyoxyethylene 20 sorbitan monooleate).

4. Lanolin and its derivatives.

The purpose and role of nPAS in the composition:

- to reduce surface tension (which improves wettability and improves the uniformity of distribution over the treated surface, creates a high degree of dispersion and stability of the aerosol when using means by aerosol spraying),

- prevents the conglomeration of bacteriophages, which contributes to the manifestation of their biological effect in vivo and increases the titer when controlling biological activity in vitro;

- to improve interaction with bacteria (reduces the protective, barrier functions of the bacterial cell wall).

- prevents the irreversible adsorption of bacteriophages on the surface of the packaging, vials during storage.

- prevents the emergence of bacteriophages to the surface (at the liquid / gas phase separation), the formation of a surface film from conglomerates of bacteriophages, thereby reducing their activity.

High molecular weight compound (IUD) (gelling agent, thickener)

It was experimentally established that IUDs that swell in water and at the same time have positive charge groups (cationogenic IUDs) in the structure significantly reduce the titer of bacteriophages (often until they are completely inactivated) and negatively affect the adsorption activity of bacteriophages during bacterial attack. IUDs of non-inogenic and / or anionic nature, forming viscous systems in water, are inert to bacteriophages and stabilize the titer and do not reduce their adsorption-lytic activity.

IUD options that meet the requirements:

- povidone and its derivatives,

- carbomer and its derivatives,

- polysaccharides and their derivatives, more preferably highly substituted hydroxypropyl methylcellulose or glucomannan.

The purpose of the IUD is at the heart of the composition: gelling agent, viscosity modifier, to ensure the necessary viscosity index (stabilizes the composition medium structure, prevents free movement, sedimentation (sedimentation, sedimentation), bacteriophage conglomeration, stabilizes during storage, increases the effect when used.

Preservative

In the course of experiments to study the effect of preservatives on the activity of bacteriophages, the following patterns were established and the following conclusions were drawn used in the described invention:

- the most pronounced inactivating effect against bacteriophages is possessed by preservatives from the group of quaternary ammonium derivatives (salts of benzalkonium, chlorhexidine, etc.), derivatives of heavy metals, oxidizing agents, bromine or iodine-containing and formaldehyde-releasing preservatives. Preservatives of these groups are not included in the composition of the present invention.

- In the group of parabens (para-hydroxybenzoic acid esters), the level of negative influence on the activity of bacteriophages decreases in the order from butylparaben to methylparaben, i.e. as lipophilicity decreases and water solubility of parabens improves. Suitable preservatives are:

methyl paraben, ethyl paraben, propyl paraben and their salts; benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone, phenoxyethanol, dichlorobenzyl alcohol, organic acids such as benzoic, sorbic, propionic, acetic, lactic, undecylenic and their salts, taken in any combination in a concentration sufficient to ensure the necessary microbial safety and toxicity corresponding to the product category. Purpose: to provide the necessary indicator of microbiological purity of the finished product.

PH regulator (corrector, pH stabilizer)

Options for Suitable pH Regulators

1. From the group of ethanolamines: diethanolamine (2,2'-iminodiethanol), triethanolamine, trolamine.

2. Sodium or potassium hydroxide.

3. Organic or inorganic acids.

Purpose: to provide a pH value optimal for the stability of bacteriophages during storage (pH 5.5 to 8.0, more preferably 6.5-7.5).

In the study of various physico-chemical factors that affect the stability of bacteriophages during storage and use, we determined the optimal parameters of the properties of the base, ensuring the stability of bacteriophages during storage, efficiency and convenience in use and application:

- The electrical conductivity of the base should be 30-900 µS (microsiemens) for a product containing carbomer as a gelling agent and 200-2000 µS for a product based on cellulose or povidone derivatives.

- Level of medium tonicity: hypotonicity-isotonicity (from 0.001 to 1.0 in terms of sodium chloride).

For hypotonic variants of the composition, it is preferable to use a carbomer as a gelling agent.

Compositions based on povidone and polysaccharides can be prepared with both hypotonic and isotonic and hypertonic environments.

- Viscosity from 50-1000 cP (centipoise) for sprays and suspensions up to 50 thousand cP for gels and application forms.

The calculation of the necessary range of viscosity of the medium for storing bacteriophages was carried out.

The minimum viscosity is determined based on the weight of bacteriophages, to prevent its sedimentation (settling to the bottom) and possible conglomeration by the interaction of bacteriophages of one or different species or the interaction of bacteriophages with the surface of the package.

The maximum viscosity is determined from the features of the application (high viscosity for thick gels, including for applications on mucous membranes).

- Redox potential from -100 to 400 mV, preferably from 20 to 200 mV.

- Acid pH from 5.5 to 8.5. More preferably 6.5-7.5.

- The content of heavy metals in total no more than 0.002%

- Microbiological purity should be: The total amount of MAFAnM in 1 g (cm ³ ), not more than 1 × 10 ³ ; bacteria of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus should be absent; yeast, yeast-like and mold fungi in 1 g (cm ³ ) not more than 1 × 10 ² .

In addition, when developing and adapting methods of using agents containing bacteriophages, the pharmacodynamics and pharmacokinetics of bacteriophages in vivo were taken into account.

When developing the invention, the issues of ensuring

energy requirements of bacteriophages during storage in a liquid medium, during movement, during attack and attachment to bacteria. The role of reactive oxygen species (ROS) in the environment of interaction between bacteriophages and bacteria consists in the energy supply of the processes of stability and movement in the environment and other vital functions of bacteriophages.

With a ROS deficiency, bacteriophages can lose activity, lytic ability. Arginine, hydrogen peroxide, ozone, ascorbic acid at a concentration of not more than 10 ^-3 M, as well as lactoferrin, glucose oxidase, and lactoperoxidase enzymes can act as prooxidants, precursors, and ROS generators in the composition of the product.

This group of substances can act as part of an antibacterial agent based on bacteriophages as stimulators of the biological activity of bacteriophages and synergists with respect to the antibacterial effect.

Thus, an important criterion for the implementation of bacteriophages in the nature of their activity is a sufficient concentration of ROS in the medium, and, consequently, the lack or absence of antioxidants and other ROS consumers.

This point has been taken into account by determining such an indicator as the ORP of the basis of the composition and by including additional components of a prooxidant nature in some variants of the composition.

Examples of compositions containing bacteriophages in various formulations

Example 1. Spray for external use

Composition, wt.%:

The complex of bacteriophages (staphylococcal, streptococcal) with Appelman lytic activity of at least 10 ^-7 0.1 carbomer 0.12 Surfactant (PEG 12 dimethicone, capric / capric triglyceride) 0.08 Preservative (benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone) 0.15

Excipients:

Prebiotic (Sorbitol) 7.0 Urea 1,5 Glycerol 2.0 D-panthenol 0.1 Cyclomethicone 2 Perfume 0.1 PH regulator (triethanolamine) to ensure pH 6.5-7.5 Purified water up to 100

Description:

low viscosity gel-like liquid with slight opalescence and a characteristic pleasant odor.

Packing: bottle with a device for spraying funds in the form of a spray.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 50-200 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.01 to 0.1

- Viscosity 100-1000 cP

- Redox potential from 20 to 250 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage not less than 10 ^-4

Appointment: for hygienic, preventive and improving care of skin of the body (face, hands, legs, back, chest).

Method of application: spray with a spray with a uniform thin layer onto the skin, if necessary, spread by hand and allow to soak and dry. Do not flush. Use as necessary, but at least 2 times a day. The duration of the course is from 2 to 5 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 2. Gel for applications (prolonged effect)

Composition, wt.%:

The complex of bacteriophages (staphylococcal, streptococcal) with Appelman lytic activity of at least 10 ^-9 0.1 IUD (hypromellose) 1,5 Surfactant (PEG 40 hydrogenated castor oil) 0.2 Preservative (sodium benzoate, potassium sorbate) 0.2 PH regulator (phosphate buffer) to ensure pH 6.5-7.5 Water up to 100

Excipients:

Perfume 0.1 Arginine 0.003 Menthol 0.01 Propylene glycol 3.0

Description:

Colorless viscous gel with a characteristic pleasant odor.

Packing: bottle with a dropper.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 300-1000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.1 to 0.3

- Viscosity 10 thousand - 50 thousand SP

- Redox potential from 100 to 400 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage is not less than 10 ^-6 .

Appointment: for intensive hygienic, preventive and health care of the oral cavity with pronounced manifestations of dysbiosis and bacterial infection - unpleasant odor and / or taste, gingivitis, periodontitis, stomatitis, caries. To reduce the risk of various inflammations and infectious complications after treatment and other intensive procedures in the oral cavity. Method of application: using a dropper, squeeze the product onto the spatula and evenly distribute it on the problem areas of the oral cavity. Do not rinse with water or drink for 1 hour. Use as necessary, but at least 2 times a day (with mandatory application for the night). The duration of the course is from 2 to 3 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 3. Gel for external use (veterinary use)

Composition, wt.%:

The complex of bacteriophages (staphylococcal, streptococcal) with Appelman lytic activity of at least 10 ^-8 0.1 IUD (carbomer) 0.3 Surfactant (PEG 12 dimethicone) 0.3 Preservative (benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone) 0.05 PH regulator (sodium hydroxide) to ensure pH 6.5-7.5 Water up to 100

Excipients:

Perfume 0.05 Cyclomethicone 3.0 Urea 1,0 Provitamin D ₃ 0.0001

Description:

Colorless viscous gel with a characteristic pleasant odor.

Packaging: bottle with dispenser, dispenser, sachet.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 100-800 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.01 to 0.2

- Viscosity 5 thousand - 30 thousand SP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage is not less than 10 ^-5 .

Appointment: for intensive hygienic, preventive and improving skin care of animals with severe inflammation, suppuration, boils and other manifestations of bacterial infection. To reduce the risk of various inflammations and infectious complications after operations, medical and other intensive procedures, injuries.

Method of application: using a dispenser, squeeze the product onto a spatula (or a cotton swab) and evenly distribute it on problem areas of the skin. Use as necessary, but at least 2 times a day. The duration of the course is from 2 to 3 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 4. Spray for the oral cavity

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, volinelny, actinobacillus, Proteaceae) with the lytic activity of not less than 10 ^-8 Appelmanu 0.1% Navy (Povidone) 7.0 Surfactant (PEG 40 hydrogenated castor oil) 0.05 PH regulator (sodium hydroxide) to ensure pH 6.5-7.0 Preservative (sodium benzoate, potassium sorbate) 0.3 Water up to 100

Excipients:

Prebiotic (fructooligosaccharide, lactulose) 8.0 Potassium lactate 2.0 D-panthenol 0.3 Fragrance (fruit and mint) 0.1

Description:

Light yellow, slightly viscous liquid with a slight opalescence and a characteristic pleasant smell and taste.

Packing: bottle with a device for spraying funds in the form of a spray.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.0

- Conductivity 300-1000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.1 to 0.3

- Viscosity 50-500 cP

- Redox potential from 50 to 150 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage is not less than 10 ^-5 per ml (cm ³ )

Appointment: for hygienic, prophylactic and improving care of the oral cavity, predisposed to various manifestations of dysbiosis - unpleasant odor and / or taste, gingivitis, periodontitis, stomatitis, caries. To reduce the risk of various inflammations and infectious complications after treatment and other intensive procedures in the oral cavity.

Method of application: irrigate the oral cavity, directing the spray to problem areas. Do not rinse with water or drink for 30 minutes. Use 3-5 times as needed, but at least 3 times a day. The duration of the course is from 2 to 5 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 5. The gel for the oral cavity

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, volinelny, actinobacillus, Protein) with Appelman lytic activity of at least 10 ^-9 0.1 IUD (hypromellose) 1,0 IUD (glucomannan) 0.4 Surfactant (PEG 40 hydrogenated castor oil) 0.1 Preservative (sodium benzoate, potassium sorbate, phenoxyethanol) 0.6 PH regulator (sodium hydroxide) to ensure pH 6.5-7.0 Water up to 100

Excipients:

Prebiotic (fructooligosaccharide, lactulose) 8.0 Potassium lactate 2.0 D-panthenol 0.3 Fragrance (citrus mint) 0.5

Description:

Colorless viscous gel with a characteristic pleasant odor and taste.

Packing: bottle with a dropper.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.0

- Conductivity 300-1000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.1 to 0.3

- Viscosity 10 thousand - 50 thousand SP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage is not less than 10 ^-6 .

Appointment: for intensive hygienic, preventive and health care of the oral cavity with pronounced manifestations of dysbiosis and bacterial infection - unpleasant odor and / or taste, gingivitis, periodontitis, stomatitis, caries. To reduce the risk of various inflammations and infectious complications after treatment and other intensive procedures in the oral cavity.

Method of application: using a dropper, squeeze the product onto the spatula and evenly distribute it on the problem areas of the oral cavity. Do not rinse with water or drink for 1 hour. Use as necessary, but at least 2 times a day (with mandatory application for the night). The duration of the course is from 2 to 3 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 6. Spray (gel) for skin care for burns

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, volinel, actinobacillus, Protein, colic, pseudomonas, acinetobacterium, enterobacterium) with lytic activity Appelman at least 10 ^-10 0.1% Navy (Povidone) 10.0 Surfactant (PEG 40 hydrogenated castor oil) 0.05 Lauret 9 0.3 PH regulator (sodium hydroxide) to ensure pH 6.5-7.0 Preservative (sodium benzoate, potassium sorbate, methyl paraben) 0.5 Water up to 100

Excipients:

Magnesium Lactate 0.3 D-panthenol 1,0 Benzocaine 3.0 Menthol 0.2 Propylene glycol 3.0 ASD fraction 2 0.5

Description:

Light yellow, slightly viscous liquid with slight opalescence.

Packing: bottle with a device for spraying funds in the form of a spray.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.0

- Conductivity 300-1000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.1 to 0.3

- Viscosity 50-500 cP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - sterility

- Appelman's lytic activity of each bacteriophage species is at least 10 ^-7 .

Appointment: for use as an auxiliary, additional tool in the complex therapy of burns of any origin (temperature, radiation, chemical). The complex of bacteriophages provides protection (in outpatient and clinical use) from infection of the inflamed area with the main pathogens of purulent bacterial infections, as well as the sanitation of an infected wound. Helps reduce the manifestations of acidosis, sensitization and toxicity of damaged tissues, stabilizes blood microcirculation.

It has an anti-inflammatory and mild analgesic effect.

Method of application: at the initial stages (necrosis, acute inflammation), apply to wound dressings until they are moistened and soaked 3-4 times a day, as well as a field for changing dressings.

In subsequent stages (scarring), apply directly to the affected area at least 3 times a day. By spraying through the spray, achieve complete wetting of the burn surface and surrounding areas. The product dries naturally, leaving a protective, gas-permeable thin coating that does not tighten the skin. Peroxides, strong oxidizing agents, chemical disinfectants, virucidal substances when applied simultaneously with the product can partially reduce its effectiveness. The spray should be applied no earlier than 20-30 minutes after their application. Duration of the course according to indications.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 7. Spray for the treatment of air and surfaces (for the disinfection of indoor air and surfaces)

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, colic, Klebsel) with lytic activity Appelman at least 10 ^-7 0.1 IUD (carbomer) 0.1 PH regulator (triethanolamip) to ensure pH 6.5-7.5 Preservative (benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone) 0.05 Surfactant (PEG 12 dimethicone) 0.2 Water up to 100

Excipients:

Perfume 0.05

Description:

low viscosity liquid with a characteristic odor.

Packing: bottle with a device for spraying funds in the form of a spray.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 50-300 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.01 to 0.1

- Viscosity 100-1000 cP

- Redox potential from 50 to 250 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage is not less than 10 ^-4 .

Appointment: for hygienic, sanitary and disinfection treatment of air and surfaces in residential, domestic and industrial premises, in places of animals, in medical and veterinary facilities, including for sanitizing antibacterial treatment of air and indoor surfaces from pathogens of nosocomial infections.

Method of application: by aerosol spraying, spray the product in the room air at the rate of 0.3-0.5 cm ^{3 of the} product per m ^{3 of the} air space of the room. To apply the product on surfaces with a high probability of seeding with bacterial pathogenic microflora and on surfaces that require special cleanliness and additional protection against contamination (based on 0.2-0.3 cm ³ per m ^{2 of the} treated surface).

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 8. Spray for the processing of food and processed foods.

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, pseudomonas, proteus, salmonella) with lytic Appelman activity of at least 10 ^-7 0.1 Navy (povidone) 3.0 Surfactant (PEG 40 hydrogenated castor oil) 0.1 Preservative (sodium benzoate, potassium sorbate) 0.3 PH regulator (sodium hydroxide) to ensure pH 6.5-7.5 Water up to 100

Excipients:

Sodium Propionate 2.0 Potassium lactate 1,0

Description:

Homogeneous yellowish liquid.

Packing: bottle spray.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 300-1000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.1 to 0.5

- Viscosity 50 s-1000 cP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage is not less than 10 ^-4 .

Purpose: for surface treatment of food products and semi-finished products in order to reduce the risk of microbial spoilage.

Method of application: with a spray, apply a thin layer on the surface of products, allow to dry naturally (without rubbing).

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 9. Gel for internal oral administration

Composition, wt.%:

A complex of bacteriophages (staphylococcal, Streptococcal, Pseudomonas aeruginosa, Proteus salmonella, citrobacter, klebsel, salmonella) with lytic activity Appelman at least 10 ^-9 1,0 IUD (hypromellose) 1,0 Navy (povidone) 5.0% Surfactant (Twin80) 0.05 Preservative (sodium benzoate, potassium sorbate) 0.3 PH regulator (sodium hydroxide) to ensure pH 6.5-7.5 Water up to 100

Excipients:

Prebiotic (fructooligosaccharide, lactulose) 5,0 Potassium lactate 1,0 Flavoring and aromatic additive 0.2

Description:

Colorless viscous gel with a characteristic pleasant odor and taste.

Packing: bottle with dispenser, tube.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 300-1000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.1 to 0.4

- Viscosity 5 thousand - 50 thousand cP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Appelman lytic activity of each type of bacteriophage not less than 10 ^-7

Appointment: prevention, treatment of gastrointestinal diseases and other internal bacterial nature.

Method of application: 1 teaspoon 2-3 times a day 30 minutes after a meal. The duration of the course is from 2 to 3 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature

0-30 ° C.

Example 10. Gel for vaginal use

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, gonococcal, gardnerellosis) with Appelman lytic activity of at least 10 ^-9 0.1 IUD (carbomer) 0.4 Surfactant (PEG 12 dimethicone) 0.1 Preservative (sodium benzoate, potassium sorbate, methyl paraben) 0.4 PH regulator (trolamine) to ensure pH 6.5-7.5 Water up to 100

Excipients:

Dimethicone 3.0 Lactulose 5,0 Oligofructose 5,0

Description:

Colorless uniform viscous gel.

Packing: bottle with dispenser, dispenser, sachet, tube.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 100-400 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.01 to 0.2

- Viscosity 5 thousand - 50 thousand cP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage not less than 10 ^-6

Appointment: for intensive hygienic, preventive and improving care of the mucous membrane of the external genital organs, predisposed to inflammatory processes and bacterial infections (bacterial vaginosis, urethritis).

Method of application: Apply 1-2 ml of gel to the mucous membranes of the external genitalia 1-3 times a day. The duration of the course is from 2 to 3 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 11. Gel for rectal administration

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, proteus, Klebselia, Pseudomonas aeruginosa) with Appelman lytic activity of at least 10 ^-9 0.1 IUD (carbomer) 0.4 IUD (hypromellose) 0.3 Surfactant (PEG 40 hydrogenated castor oil) 0.2 Preservative (sodium benzoate, potassium sorbate, methyl paraben) 0.4 PH regulator (triethanolamine) to ensure pH 6.5-7.5 Water up to 100

Excipients:

Urea 0.5

Description:

Homogeneous gel.

Packing: bottle with dispenser, dispenser, tube.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Electrical conductivity 100 -800 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.01 to 0.2

- Viscosity 10 thousand - 40 thousand cP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Appelman's lytic activity of each type of bacteriophage is not less than 10 ^-6 )

Appointment: for prevention, treatment of bacterial infections.

Method of application: a single dose of 1-5 ml of gel, which is used undiluted or diluted with 5 times the amount of water. Enter per rectum with an enema. Use in accordance with the instructions, but at least 1 time per day. The duration of the course is from 2 to 3 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 12. Concentrate, prefabricated for production

Composition, wt.%:

A complex of bacteriophages (of any composition) with Appelman lytic activity of at least 10 ^-10 1.0-10.0 Navy (povidone) 15.0 Surfactant (PEG 40 hydrogenated castor oil) 0,07 Preservative (benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone) 0.05 PH regulator (sodium hydroxide) to ensure pH 6.0-7.5 Water up to 100

Description:

Homogeneous yellowish liquid

Packing: bottle

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 100-1000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.01 to 0.2

- Viscosity 50 s - 1000 cP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Appelman lytic activity of each type of bacteriophage not less than 10 ^-7

Appointment: for use as a concentrate (semi-finished product) of bacteriophages. It is used in the production of finished products.

Method of application: add to the composition of the product in accordance with the approved recipe and technological instructions.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 13. Spray to protect plants from bacterial infections

Composition, wt.%:

A complex of bacteriophages active against (Corynebacter, Erwinia, Pseudomonas, Xanthomonas) with Appelman lytic activity of at least 10 ^-7 0.1 IUD (carbomer) 0.05 Navy (povidone) 1,0 PH regulator (triethanolamine) to ensure pH 6.0-7.5 Preservative (benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone) 0.05 Surfactant (PEG 12 dimethicone) - 0.05 Water up to 100

Excipients:

glycerol 2.0

Description:

low viscosity liquid, almost odorless.

Packing: bottle with a device for spraying funds in the form of a spray.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.0-7.5

- Electrical conductivity 50-500 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.01 to 0.1

- Viscosity 100-1000 cP

- Redox potential from 50 to 250 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - meets the requirements

- Lytic activity according to Appelman of each type of bacteriophage not less than 10 ^-4

Appointment: for processing plants for the purpose of protection and treatment against bacterial infections.

Method of application: by aerosol spraying, spray the product on the surface of the plants, achieving uniform wetting. Multiplicity of use at least 2 times a day. The duration of the course is 2-4 weeks.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0-30 ° C.

Example 14 Atraumatic gel dressing for topical treatment of wounds, burns and skin diseases. The dressing consists of a textile base (polyamide mesh), impregnated with a gel-like composition (according to example 2).

Example 15 Eye Drops with Antibacterial Effect

Composition, wt.%:

A complex of bacteriophages (staphylococcal, streptococcal, colic, pseudomonas) with Appelman lytic activity of at least 10 ^-10 0.1% Navy (Povidone) 5,0 Hypromellose 0.3 Surfactant (PEG 40 hydrogenated castor oil) 0.08 Lauret 9 0.12 PH regulator (phosphate buffer) to ensure pH 6.5-7.5 Preservative (sodium methylparaben, naryl propylparaben) 0.25 Water up to 100

Excipients:

D-panthenol 0.5 Sodium Chloride 0.85

Description:

Colorless to light yellow, low viscosity, homogeneous liquid.

Packing: bottle with dropper nozzle.

Physico-chemical and microbiological characteristics of the product

- Acid pH 6.5-7.5

- Conductivity 800-2000 µS

- The level of tonicity of the medium in terms of sodium chloride from 0.85 to 0.95

- Viscosity 500-2000 cP

- Redox potential from 50 to 300 mV

- The content of heavy metals in total no more than 0.002%

- Microbiological purity - sterility

- Appelman lytic activity of each type of bacteriophage not less than 10 ^-7

Appointment: For use as the main, auxiliary or additional means in complex therapy and prevention of bacterial infections of the eyes. It has an additional anti-inflammatory and mild analgesic effect.

Method of application: 1-3 drops in each eye 2-3 times a day.

Shelf life: at least 2 years when stored in a dark place at a temperature of 0 to 30 ° C.

Advantages and novelty of the invention:

- the ability to obtain various finished forms with different consistencies, organoleptic properties on equipment with standard equipment for soft and liquid forms of medicines or cosmetics;

- obtaining aerosols with a high degree of dispersion (which ensures a long stay in suspension in the air, uniform wetting, fine distribution over the surface) - this increases the efficiency;

- obtaining uniform thin films on the surface (by wetting the skin, mucous membranes, objects), after drying the films on environmental objects, bacteriophages can retain biological activity against pathogenic microorganisms for a long time and, when favorable conditions are created, show their lytic activity. High good wettability of the treated surfaces and adhesion to them;

- the optimal physicochemical criteria for the stability of bacteriophages during storage and use were taken into account;

- the shelf life is more than 1 year and up to 3 years for most of the proposed options, which exceeds the stability and recommended shelf life for most products with bacteriophages (on average, from 6 to 18 months when stored in a refrigerator);

- The temperature range for storage and use of bacteriophages has been expanded. The composition can be stored in a wide temperature range from 0 to + 30 ° C. For viscous forms (for application) and means for the oral cavity, freezing and short-term storage at plus 35 ° C are allowed;

- expanding the possibilities for obtaining products based on bacteriophages with various variants of administration and methods of practical use - external or internal use, application or aerosol application method, for people or animals or plants, for treating surfaces or food products;

- taken into account the positive use of prooxidants and ROS producers in relation to the activity of bacteriophages and the negativity of the presence of high concentrations of antioxidants in the composition;

- the exact requirements to the properties of the components of the base of the agents with bacteriophages were determined: the use of surfactants of only nonionic nature is allowed, the use of IUDs (gelling agents) containing cationic groups is not allowed.

- clearly defined range of preservatives acceptable for use.

- determined the optimal range of concentration of substances of the base from the minimum necessary to a sufficient concentration in the tool. The recommended concentration of surfactants is reduced in comparison with analogues.

The invention allows to expand the range of products containing highly selective natural antibacterial components (bacteriophages) as the main active principle, to ensure biological stability and activity of bacteriophages in the composition of the product. In addition, the composition has a low risk of toxic and side effects, allows you to expand options and methods for the practical use of agents containing bacteriophages, provides storage stability and efficiency in a wide temperature range.

Claims (11)

1. An antibacterial agent containing a concentrate of bacteriophages, a gelling agent in the form of a nonionic or anionic high molecular weight compound, a nonionic surfactant, any preservative other than those related to derivatives of quaternary ammonium bases, derivatives of heavy metals, oxidizing agents, bromine or iodine-containing, formaldehyde-releasing preservatives, pH regulator and water in the following ratio of components, wt.%:
bacteriophage concentrate with lytic activity Appelman at least 10 ^-4 for each type of bacteriophage 0.001-10.0 gelling agent 0.05-15.0 Surfactant 0.001-2.0 preservative 0.05-0.6 pH regulator to ensure pH 6.0-8.0 water up to 100.0 2. The antibacterial agent according to claim 1, characterized in that it contains a carbomer as a gelling agent, a copolymer of silicone and glycol (preferably PEG 12 dimethicone) as a surfactant, triethanolamine as a pH regulator and a complex of benzyl alcohol, methylchloroisothiazolinone, methylisothiazolinone as a preservative in the following ratio of components, wt.%:
bacteriophage concentrate with lytic activity Appelman at least 10 ^-7 0.1-0.2 carbomer 0.05-0.6 silicone glycol copolymer 0.01-0.3 preservative 0.05-0.2 triethanolamine to ensure pH 6.0-8.0 water up to 100.0 3. The antibacterial agent according to claim 1, characterized in that it contains hypromellose as a gelling agent, a surfactant selected from the group of ethoxylated vegetable oils and / or ethoxylated fatty acids and / or ethoxylated alcohols, a phosphate buffer as a pH regulator and a complex sodium benzoate and potassium sorbate as a preservative in the following ratio of components, wt.%:
bacteriophage concentrate with lytic activity Appelman at least 10 ^-9 0.1-0.2 hypromellose 0.3-2.0 Surfactant 0.1-0.3 preservative 0.2-0.4 phosphate buffer to ensure pH 6.5-7.5 water up to 100.0 4. The antibacterial agent according to claim 1, characterized in that it contains glucomannan as a gelling agent, PEG 40 hydrogenated castor oil as a surfactant, sodium hydroxide as a pH regulator, a complex of sodium benzoate and phenoxyethanol as a preservative in the following ratio of components, wt .%:
bacteriophage concentrate with lytic activity Appelman at least 10 ^-9 0.1-0.2 glucomannan 0.3-2.0 PEG 40 hydrogenated castor oil 0.01-0.1 preservative 0.2-0.6 sodium hydroxide to ensure pH 6.0-7.5 water up to 100 5. The antibacterial agent according to claim 1, characterized in that it contains povidone as a gelling agent, surfactants from the group of polyoxyethylene sorbitan fatty acids (preferably tween 80), sodium hydroxide as a pH regulator and potassium sorbate as a preservative in the following ratio of components, wt .%:
bacteriophage concentrate with lytic activity Appelman at least 10 ^-9 1.0-1.5 povidone 1.0-7.0 Surfactant 0.01-0.1 potassium sorbate 0.1-0.4 sodium hydroxide to ensure pH 6.0-7.5 water up to 100 6. The antibacterial agent according to claim 1, characterized in that it contains povidone as a gelling agent, surfactants selected from the group of ethoxylated vegetable oils and / or ethoxylated fatty acids and / or ethoxylated alcohols, sodium hydroxide as a pH regulator and complex sodium salts of methylparaben and propylparaben as a preservative in the following ratio of components, wt.%:
bacteriophage concentrate with lytic activity Appelman at least 10 ^-10 0.1-10.0 povidone 5.0-15.0 Surfactant 0.01-0.3 lauret-9 0.01-0.3 preservative 0.1-0.4 sodium hydroxide to ensure pH 6.0-7.5 water up to 100 7. The antibacterial agent according to any one of claims 1 to 6, characterized in that it contains a humectant from the group of polyhydric alcohols and / or salts of organic acids in an amount of 0.5-6.0 wt.%. 8. An antibacterial agent according to any one of claims 1 to 6, characterized in that it contains a substance with a prebiotic effect against normoflora in an amount of 0.5-10.0 wt.%. 9. The antibacterial agent according to any one of claims 1 to 6, characterized in that it contains a sweetener and / or flavor in an amount of 0.01-5.0 wt.%. 10. An antibacterial agent according to any one of claims 1 to 6, characterized in that it contains non-ionic pharmaceutical substances having local anesthetizing and / or hypersensitizing properties (preferably benzocaine, novocaine, diphenhydramine, menthol) in an amount of 0.05-5.0 wt. .%. 11. An antibacterial agent according to any one of claims 1 to 6, characterized in that it contains prooxidants and / or generators of reactive oxygen species (preferably arginine, hydrogen peroxide, ascorbic acid, lactoferrin, glucose oxidase, lactoperoxidase) in an amount not higher than 0.02 wt.%.