RU2443431C1 - Method for preventing and treating influenza in pre-epidemic and epidemic environment and related drug preparation for implementation thereof - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to pharmaceutics. The method involves introducing a liposome-containing drug preparation. The liposome-containing drug preparation contains a dispersion of unilamellar liposomes prepared of a suspension of multilamellar liposomes of phospholipid group similar in composition with human cell membrane phospholipids. Linear size of the unilamellar liposomes are specified in view of the conformity to linear size of influenza virions.

EFFECT: method and drug preparation provide virus inhibitory action in consistently changing antigenic structure of various influenza virus strains and eliminate hepatotoxic action by immediate effect on lipid membrane of influenza virus.

17 cl, 2 dwg, 2 tbl, 4 ex

Description

The invention relates to medicine and biotechnology and can be used for the prevention and treatment of influenza during pre-epidemic and epidemic periods.

Influenza and acute respiratory viral infections (ARVI), despite some success in vaccine and chemoprophylaxis, remain one of the most pressing medical and socio-economic problems. In Russia, influenza and ARVI account for up to 90% of the total annual incidence rate. WHO predicts the emergence of a new antigenic variant of the influenza virus and the possibility of a pandemic with a multiple increase in the incidence. Cases of human exposure to animal influenza virus, in particular avian influenza virus, continue to occur. Influenza virions adapted to laboratory hosts are particles of an almost spherical shape with a diameter of about 100 nm. Strains freshly isolated from humans usually have the appearance of long threads.

The following chemotherapeutic agents are currently used for the prevention and treatment of influenza: Oxolinic ointment, Arbidol, Remantadin, Tamiflu and other influenza virus neuraminidase inhibitors, as well as Kogacel, a drug containing alpha-interferon that activates cellular and humoral immunity. However, the use of these drugs is limited by the evolution of the influenza virus, i.e. the emergence of "genetically new" neuraminidases.

In biotechnology, the use of liposomes is known - smectic phases in which water separates phospholipid bilayers. Unlike micelles, they are not dynamic. If liposomes are formed, they do not dissociate into their constituent lipids. This feature allows you to use them as nanotransporters, including for the treatment of viral infections (Kontarov N.A., et al. Study of the interaction of boraadamantane with liposomes. Biophysics, 2010, 55, 2, 269-270). So, in the application (BG 51003 (A1), KAVAKLOVA LILJANA et al., January 15, 1993) describes the process of obtaining a virosomal vaccine for the prevention of influenza using liposomes as carriers of viral antigens: hemagglutinin and neuraminidase. The disadvantage of virosomal vaccines is that the active ingredient is influenza antigens, and not virosome phospholipids. In the patent US 6391318 (B1) ILLUM LISBETH et al., 05/21/2002, describes a method for producing vaccine compositions based on liposomes with embedding in them the heavy chain of the viral antigen - hemagglutinin, as well as chitosan. Application (EP 0047480 (A2) THIBODEAU LISE, 03/17/1982) describes the preparation of so-called immunoliposomes, i.e. liposomes loaded with T-lymphocyte epitopes that take part in the immune response to a strain of influenza virus of a certain antigenic composition.

An analysis of these sources shows that liposomes act only as carriers of immune components, and influenza antigens are the vector of action of these drugs.

The present group of inventions is aimed at creating a method and preparation for the treatment and prophylaxis of influenza virus, based on the mechanism of liposome inactivation of the hemagglutinating ability of influenza virions. The interaction of the liposome and virion leads to the extraction of a significant amount of cholesterol into the lipid bilayer of liposomes, which is a part of virion membranes. This is supported by a decrease in the lipid content in the membranes of virions in contact with liposomes. Extraction of cholesterol into liposomes leads to a decrease in the viscosity of the lipid bilayer of virions, to the appearance of a difference in the curvatures of the outer and inner lipid layers of the virions, which in turn causes the disintegration and disorientation of hemagglutinins, and subsequently the destruction of the virions themselves. The ratio of virions that are simultaneously in contact with adsorbed liposomes (according to electron microscopy no more than 20-30%) and zero hemagglutinating titer of the virus is noteworthy. 70-80% of virions, having morphologically intact hemagglutinins, nevertheless lose their hemagglutinating activity. This circumstance may indicate the presence of conformational changes in the structure of hemagglutinin molecules caused by short-term contact of virions with liposomes. However, these changes play a greater role in the process of inhibition of the virus than morphologically expressed destructive changes of 20-30% of the virions contained in the preparations.

An advantage of the developed liposomal preparations is the independence of their virus-inhibiting effect from the constantly changing antigenic structure of various strains of influenza viruses.

A patented method for the prevention and treatment of influenza consists in the introduction of a liposome-containing preparation, which includes a dispersion of single-layer liposomes obtained from a suspension of multilayer liposomes of the phospholipid group, identical in composition to the phospholipids of the cell membranes of the human body, while the linear sizes of single-layer liposomes are selected from the condition that the linear sizes of influenza virions are linear.

The method can be characterized in that the group of phospholipids includes phosphatidylcholine, phosphatidylethanolamine, dipalmitoylphosphatidylcholine obtained from naturally occurring lecithins and / or cephalins, as well as the fact that multilayer liposomes are obtained from dry phospholipids by dissolving them in a solution of 0.01 MCl and incubating with 0.01 KCl 60-70 ° C for at least 10 minutes with continuous shaking until opalescence.

The method can also be characterized by the fact that a suspension of multilayer liposomes is obtained from a mixture of phospholipids - dipalmitoylphosphatidylcholine and phosphatidylethanolamine in a molar ratio of 1: 2, and also that a dispersion of single-layer liposomes is obtained from a suspension of multilayer liposomes by ultrasonic dispersion of the same sizes until the last linear range 25-100 nm.

The method can be characterized, in addition, by the fact that the dispersion of single-layer liposomes further includes a stabilizer-gelling agent, namely a solution of low molecular weight polyethylene glycol PEG-400 with a concentration of 1.5-2.5 mmol per 1 ml of dispersion, and that intranasal and / or mucosal, as well as parenteral methods of drug administration.

The method can be characterized by the fact that, for prophylactic purposes, the dispersion of single-layer liposomes is used in a single dose of 1-10 ml with a concentration of 4-6 mg / ml, 2-3 times a day, and when the first signs of infection appear, the nasal cavity and / or nasopharynx are irrigated dispersion of single-layer liposomes with a single dose of 1-10 ml with a concentration of 10 mg / ml, 5 times a day. In the acute phase of the disease, irrigation of the nasal cavity and / or nasopharynx alternates with the dispersion of single-layer liposomes with a gel stabilizer every 3-4 hours.

A liposome-containing preparation for the prevention and treatment of influenza includes a dispersion of single-layer liposomes obtained from multilayer liposomes of the phospholipid group, identical in composition to the phospholipids of the cell membranes of the human body, and the linear sizes of single-layer liposomes are selected from the condition that they correspond to the linear sizes of influenza virions. The phospholipid group may include phosphatidylcholine, phosphatidylethanolamine, dipalmitoylphosphatidylcholine derived from lecithins and cephalins of natural or artificial origin.

Multilayer liposomes can be obtained from dry phospholipids by dissolving them in a solution of 0.01 M KCl and incubating at 60-70 ° C for 10-15 minutes with continuous shaking until opalescence appears, and a suspension of multilayer liposomes is obtained from a mixture of phospholipids-dipalmitoylphosphatidylcholine and phosphatidylethanolamine in a molar ratio of 1: 2.

A patented preparation may be characterized in that the dispersion of single-layer liposomes is obtained from a suspension of multi-layer liposomes by ultrasonic dispersion of the latter to achieve linear sizes of single-layer liposomes in the range of 25-100 nm, and also includes the addition of a stabilizer-gelling solution of low molecular weight PEG-400 polyethylene glycol with a concentration of 1.5-2.5 mmol per 1 ml of dispersion.

The technical result of the group of inventions is the effect directly on the lipid membrane of the influenza virus for a virus-inhibiting effect, which ensures the effectiveness of the antiviral drug in the conditions of the constantly changing antigenic structure of various strains of influenza viruses and the exclusion of the hepatotoxic effect inherent in chemotherapeutic agents. In many currently available drugs, the antiviral effect consists precisely in influencing the antigenic proteins of the influenza virus.

The invention is illustrated in the drawings, where

figure 1 shows electron microscopic images of influenza virions; a) a group of virions; b) a separate virion. Scale bar - 100 nm;

figure 2 - electron-microscopic image of the interaction of native liposomes with virions of the influenza virus and their destructive changes;

a), b) - the initial stages of the interaction of native liposomes with virions; c), d) - final stages.

Preparation of single-layer liposomes of a given size includes the following stages.

1. Preparation of the initial multilayer liposomes, identical in composition to the phospholipids of the cell membranes of the human body.

For the preparation of native liquid liposomes, both natural (egg lecithin, egg phosphatidylcholine) and synthetic (phosphatidylcholine) lecithins and (phosphatidylethanolamine) cephalins are used. If liposomes are prepared from dry phospholipids (for example, manufactured by Sigma (USA): dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylcholine and phosphatidylethanolamine, taken in a molar ratio of 1: 2, they are dissolved in a solution of 0.01 M KCl and incubated at a temperature transition temperature above the phosphol phase (usually at a temperature not lower than 70 ° C) with continuous shaking for at least 10 minutes until the appearance of visible opalescence.

The result is a suspension of multilayer liposomes.

2. Processing a suspension of multilayer liposomes according to claim 1 to obtain a dispersion of small single-layer liposomes (size up to 100 nm). To ensure the linear dimensions of liposomes and the linear sizes of influenza virions, the suspension of multilayer liposomes is treated with an ultrasonic disperser of the UZDN-A type (NPP Ukrrospribor) for 2-3 minutes. The size of liposomes and their concentration during processing is controlled by the spectrum of the turbidity of the suspension (Kontarov N.A. et al. A new method for measuring the size and concentration of liposomes. // Journal of Microbiology, Epidemiology and Immunobiology. 2009, 6, pp. 95-98) using a Zenyth 200st spectrophotometer and an RPL-3 refractometer to measure the refractive index of the suspension.

For comparison, the estimation of the size of the obtained liposomes is also carried out using electron microscopy. To do this, the liposome dispersion is adsorbed on a carbon stabilized formar film. After washing three times with phosphate buffer (pH 7.2), FBI No. 2 (NPO Mikrogen, Moscow) contrasted the material with phosphoric tungsten acid (pH 7.0-7.2). Further processing of electron microscopic nets is carried out according to the usual scheme.

As a result, a dispersion of single-layer liposomes with linear dimensions in the range of 25-100 nm can be obtained. In order to identify the peroxidation of phospholipids, which is possible after ultrasonic treatment under sterile conditions of liposomal dispersion, the chemiluminescent method is used. To further ensure the sterility of the preparation, the obtained liposomal dispersions are passed through filters with an appropriate pore diameter and high hydrophobicity (domestic filters (Dubna) or Millipor (USA)), through which only small single-layer liposomes with an average diameter of 20-40 nm can pass. After filtration, the sterile liposome dispersion is poured into vials. The resulting native liposomes should be used within 1 day before they retain opalescence, or lyophilized and stored at a temperature of minus 20 ° С.

3. Stabilization of the dispersion structure of single-layer liposomes obtained according to claim 2, if necessary, store the stock until use. For this, a stabilizer-gelling agent is introduced into the dispersion of single-layer liposomes: a solution of low molecular weight PEG-400 polyethylene glycol with a concentration of 1.5-2.5 mM per 1 ml of liposome dispersion.

The achievement of the technical result of the patented group of inventions is justified by the following results of liposome inhibition of the infectious and hemagglutinating activity of influenza virions:

- in model experiments on liposome dispersion;

- on transplantable cell culture MDCK;

- on the primary culture of chicken embryo fibroblasts (FCE);

- on laboratory animals - Balb / c mice.

The following strains of the envelope influenza virus were used in the experiments, including those that today detect a pandemic danger to humans:

- A strain of avian plague virus A / VChP / Weybridge (H7N7);

- The strain of avian influenza virus A / Mallard Pennsylvania / 102118/84 (H5N2);

- The strain of avian influenza virus A / NIBRG-14 (H5N1).

Viruses were grown on 10-day-old chicken embryos.

The following results are obtained.

1. Model experiments on the dispersion of single-layer liposomes. In model experiments, to study the interaction of liposomes with influenza virions, a film-substrate of a JEM 100-CY electron microscope (JEOD, Japan) with an instrumental magnification of 58000-100000 is used as a mesh and photographs are taken on AQFA Camera CE film. To do this, the material is adsorbed on a carbon stabilized form film. After 3 times washing with PBS No. 2 (pH 7.2), the material is contrasted with phosphoric tungsten acid (pH 7.0-7.2). When studying the process of interaction of liposomes with avian influenza virus virions, virus particles are adsorbed on the film, then the net is placed on a drop of liposome-containing mixture and incubated for 5 min at room temperature. Further processing of electron microscopic nets is carried out as described above. Effective against influenza viruses, liposome concentrations are in the range of 0.1 mg / ml - 10 mg / ml, linear sizes of liposomes were 25-100 nm, virions - 100-160 nm (figure 1, 2).

In experimental preparations, viral particles of 4 types are detected - see figure 2: a), b) - virions with cholesterol-free liposomes adsorbed on the surface of virions; c) virions with liposomes adsorbed on their surface and a partially destroyed layer of hemagglutinins; d) completely destroyed virions with a partially preserved surface membrane containing a few degraded hemagglutinins.

Therefore, the interaction of single-layer liposomes with virions leads to a weakening of their functional activity until its termination.

2. Experiments on transplantable cell culture MDCK. Study of the virus-inhibiting effect of native liposomes. A number of experiments were carried out to study the virus-inhibiting effect of liposomes from dipalmitoylphosphatidylcholine and phosphatidylethanolamine in a 1: 2 ratio on MDCK cells infected with avian plague virus (strain A / ICP / Weybridge). The titer of the hemagglutinating activity of viruses is determined by the micromethod in the hemagglutination reaction with a 0.5% suspension of chicken red blood cells and identification by plaques in a 72-hour culture of PCF and in 10-day-old chicken embryos when they are infected in the allantoic cavity. The infectious titer is calculated by the Reed-Mench method as modified by Thompson (Thompson WR, 1947). At the initial stage of this study, the propagation of avian plague virus in the presence of liposomes in the RPMI-1640 support medium was studied. For this purpose, a monolayer of MDCK cells was infected with avian plague virus with a multiplicity of infection of 0.01-0.1 EID50 / cell, the cell concentration was 2.5-3.0 · 10 ⁶ cells / ml. Adsorption lasted 30 minutes at room temperature. Then the virus was washed thoroughly and RPMI-1640 medium containing liposome dispersion (2 mg / ml) was added to the mattresses.

Virus-infected cells in the presence of RPMI-1640 medium containing native liposomes were used as a control. Infected cells were incubated for four days at a temperature of 37 ° C. Daily conducted a study of the state of cells under a microscope and determined the infectious titer and titer of hemagglutinating units in the medium.

It was shown that the infectious titer and the titer of hemagglutinating units irreversibly decreases to zero by the fourth day.

3. The result obtained on the transplanted MDCK cell culture described in paragraph 2 above is fully confirmed on another cell culture — the primary culture of chicken embryo fibroblasts (PCE). The infectious titer and the titer of hemagglutinating units was determined by the methods described in paragraph 2.

4. Experiments on laboratory animals - Balb / c mice. In the experiments used 500 individuals.

The concentrations of native liposomes (NL), stabilized liposomes (SL) and their injected volume for the prevention and treatment of influenza were established on laboratory animals - Balb / c mice, and then a corresponding recalculation of the concentrations and volume of a single dose for humans was carried out based on the ratio of human body weight 60-80 kg to the weight of the laboratory animal 8-10 g, amounting to about 10,000, from the ratio of the surface or volume of the nostril space in humans and in the laboratory animal, equal to about 150-200.

Laboratory animals - mice of the Balb / c line weighing 8-10 g - are pre-infected intranasally with doses of 21 g EID ₅₀ / ml and 41g EID ₅₀ / ml strain A / Mallard / Pennsylvania / 10218/84 avian influenza virus H ₅ N ₂ adapted to the mice of this line. It was previously established that intranasal administration to mice of that dose line at 21 g of EID ₅₀ / ml causes the death of animals on days 5-6, and intranasal administration of a dose of 41 g EID ₅₀ / ml on 3-4 days. As a control, a group of animals infected with the indicated doses of the virus is observed, as well as a group of uninfected animals. Mice under mild ether anesthesia are injected with virus-containing fluid in a volume of 20 μl into each nostril. After 6 hours, the test drugs are administered to infected animals. A dispersion of NL with a concentration of 1 mg / ml phospholipids is injected in a volume of 20 μl into each nostril of the animal. For animals, the drug is administered daily once a day for 7 days.

The possibility of mucosal and parenteral methods of NL administration was investigated. After intranasal infection of Balb / c mice with doses of 21 g EID ₅₀ / ml and 41 g EID ₅₀ / ml avian influenza virus H ₅ N ₂ , intranasal and mucosal methods of NL administration are used for therapeutic purposes. Intranasal administration of NL is carried out at a concentration of 1 mg / ml.

Parenteral administration of the drug is carried out in the thigh muscle. The drug is administered to animals for 7 days. It is possible to use both intranasal and / or mucosal and parenteral administration methods. A significant decrease in the mortality rate of infected laboratory animals infected with the influenza virus after administration of various doses of NL by various methods shows the virus-inhibiting effect of native liposomes. Table 1 presents the results on the effect of NL obtained from dipalmitoylphosphatidylcholine and phosphatidylethanolamine (in a molar ratio of 1: 2, respectively) on the propagation of the strain of avian plague virus A / VChP / Weybridge (H7N7) in MDCK cells. Table 2 presents the results of a study of the virulence of strain A / Mallard / Pennsylvania / 10218/84 of bird flu virus for Balb / c mice with intranasal administration of liposomes.

Production example. Dry phospholipids manufactured by Sigma (USA): dipalmitoylphosphatidylcholine and phosphatidylethanolamine (in a 1: 2 molar ratio) in an amount of 200 mg are dissolved in 50 ml of a 0.01 M sterile KCl solution, incubated at a temperature of 70 ± 1 ° C with continuous shaking for 10 minutes before visible opalescence.

The resulting suspension of multilayer liposomes is treated with an ultrasonic disperser UZDN-A for 2-3 minutes.

The sizes of the obtained single-layer liposomes and their concentration in the dispersion during processing are controlled by the spectrum of the turbidity of the suspension, and the detection of possible peroxidation of phospholipids is carried out by the chemiluminescent method. To further ensure the sterility of the preparation, the obtained dispersions are passed through molecular filters with an average pore diameter of 20-40 nm and high hydrophobicity. After filtration, the sterile dispersion is poured into vials with a nominal volume of 10-50 ml or lyophilized and packaged in ampoules.

The lyophilized preparation in ampoules is diluted with an appropriate volume of saline and used for intranasal use. A single dose of the drug is 1-10 ml with a concentration of single-layer liposomes 4-6 mg / ml, 2-3 times a day intranasally with a preventive purpose for a month. When the first signs of infection appear, the drug is used intranasally and / or for rinsing the nasopharynx with a single dose of 1-10 ml of liposomal dispersion with a concentration of single-layer liposomes of 4-6 mg / ml 5 times a day until the symptoms of the disease disappear. Rinsing the nasopharynx is carried out 5-10 ml of the drug for 1-1.5 minutes, intranasal administration is carried out by a dropper-dispenser.

Application examples

Example 1. Prophylactic administration in the pre-epidemic period A lyophilized preparation is diluted with an appropriate volume of physiological saline and used for intranasal use. A single dose of the drug is 1-10 ml with a concentration of single-layer liposomes 4-6 mg / ml, 2-3 times a day intranasally, for a month.

Example 2. When an epidemic occurs, at the first sign of infection, the nasal cavity and / or nasopharynx are irrigated with a dispersion of single-layer liposomes with a single dose of 5 ml, a concentration of 10 mg / ml, 5 times a day. For this, as in example 1, the lyophilized preparation is diluted with saline and used for at least 3 days.

Example 3. In the acute phase of the disease of influenza, irrigation of the nasal cavity and / or nasopharynx is carried out by dispersion of single-layer liposomes with a gel stabilizer every 3-4 hours until recovery.

Thus, the use of the described single-layer liposomes as a means of preventing and treating influenza will cause a decrease in the incidence in the event of an epidemic and pandemic. In addition, the need to predict the emergence of new strains of the virus due to mutations is practically nullified, since the vector of the virus-inhibiting action of liposomes is directed to the lipid membrane of the virus, and not to antigenic proteins, as in many currently available drugs. The use of single-layer liposomes as a biocompatible and biodegradable preparation allows their prolonged use.

Table 1 The effect of liposomes from dipalmitoylphosphatidylcholine and phosphatidylethanolamine (in a molar ratio of 1: 2) on the propagation of the strain of avian plague virus A / VChP / Weybridge (H ₇ N ₇ ) in MDCK cells The composition of the supporting environment GAE virus titer / ml (lg EID ₅₀ / ml) after infection 2nd day 3rd day 4th day one RPMI-1640 environment 64 (4.00 ± 0.02) 128 (4.00 ± 0.02) 128 (4.00 ± 0.02) 2 RPMI-1640 medium + liposomes (1 mg / ml) 64 (4.00 ± 0.02) 0 (0) 0 (0)

table 2 Virulence of strain A / Mallard / Pennsylvania / 10218/84 of avian influenza virus for white Balb / c mice with intranasal administration of a therapeutic dose of liposomes Dose of administration The survival rate of animals at various times after the introduction of the virus,% 1st day 2nd day 3rd day 4th day 7th day Glanz significance test, Z 21 g EID ₅₀ / ml one hundred one hundred one hundred one hundred 99 2,3 31 g EID ₅₀ / ml one hundred one hundred one hundred one hundred 98 2.2 41 g EID ₅₀ / ml one hundred one hundred one hundred one hundred 95 4.2 51 g EID ₅₀ / ml one hundred one hundred one hundred 97 95 3,5 61 g EID ₅₀ / ml one hundred one hundred one hundred 95 92 4.4 The control one hundred one hundred one hundred one hundred one hundred -

Claims (17)

1. The method of prevention and treatment of influenza, consisting in the introduction of a liposome-containing preparation, characterized in that the liposome-containing preparation comprises a dispersion of single-layer liposomes obtained from a suspension of multilayer liposomes of the group of phospholipids identical in composition to the phospholipids of the cell membranes of the human body, while the linear dimensions of single-layer liposomes are selected from matching conditions for linear sizes of influenza virions. 2. The method according to claim 1, characterized in that the group of phospholipids includes phosphatidylcholine, phosphatidylethanolamine, dipalmitoylphosphatidylcholine obtained from natural lecithins and / or artificial cephalins. 3. The method according to claim 1, characterized in that the multilayer liposomes are obtained from dry phospholipids by dissolving them in a solution of 0.01 M KCl and incubating at 60-70 ° C for at least 10 minutes with continuous shaking until opalescence. 4. The method according to claim 1, characterized in that the suspension of multilayer liposomes is obtained from a mixture of phospholipids - dipalmitoylphosphatidylcholine and phosphatidylethanolamine in a molar ratio of 1: 2. 5. The method according to claim 1, characterized in that the dispersion of single-layer liposomes is obtained from a suspension of multi-layer liposomes by ultrasonic dispersion of the latter to achieve linear sizes of single-layer liposomes in the range of 25-100 nm. 6. The method according to claim 1, characterized in that the dispersion of single-layer liposomes further includes a stabilizer - a gel former - a solution of low molecular weight polyethylene glycol PEG-400 with a concentration of 1.5-2.5 mm per 1 ml of dispersion. 7. The method according to claim 1, characterized in that use the intranasal and / or mucosal method of administration of the drug. 8. The method according to claim 1, characterized in that use the parenteral method of administration of the drug. 9. The method according to claim 1, characterized in that for prophylactic purposes, the dispersion of single-layer liposomes is used in a single dose of 1-10 ml with a concentration of 4-6 mg / ml, 2-3 times a day. 10. The method according to claim 1, characterized in that when the first signs of infection appear, the nasal cavity and / or nasopharynx are irrigated with a dispersion of single-layer liposomes with a single dose of 1-10 ml with a concentration of 10 mg / ml, 5 times a day. 11. The method according to claim 6, characterized in that in the acute phase of the disease, irrigation of the nasal cavity and / or nasopharynx is alternated by dispersion of single-layer liposomes with a stabilizer-gelling agent, every 3-4 hours 12. Liposome-containing preparation for the prevention and treatment of influenza according to claim 1, which includes a dispersion of single-layer liposomes obtained from multilayer liposomes of the phospholipid group, identical in composition to the phospholipids of the cell membranes of the human body, and the linear dimensions of single-layer liposomes are selected from the condition that the linear sizes of influenza virions correspond to linear sizes. 13. The drug according to item 12, in which the group of phospholipids includes phosphatidylcholine, phosphatidylethanolamine, dipalmitoylphosphatidylcholine obtained from lecithins and / or cephalins of natural or artificial origin. 14. The drug according to item 12, in which multilayer liposomes are obtained from dry phospholipids by dissolving them in a solution of 0.01 M KCl and incubating at 60-70 ° C for 10-15 minutes with continuous shaking until opalescence. 15. The drug according to item 12, in which the suspension of multilayer liposomes is obtained from a mixture of phospholipids - dipalmitoylphosphatidylcholine and phosphatidylethanolamine in a molar ratio of 1: 2. 16. The drug according to item 12, in which the dispersion of single-layer liposomes is obtained from a suspension of multi-layer liposomes by ultrasonic dispersion of the latter to achieve linear sizes of single-layer liposomes in the range of 25-100 nm. 17. The drug according to item 12, characterized in that it further includes a stabilizer - gelling agent - a solution of low molecular weight polyethylene glycol PEG-400 with a concentration of 1.5-2.5 mm per 1 ml of dispersion.

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