RU2609734C2 - Pneumatic generator of liquid aerosol particles and aqueous solution of hydrophobic compounds of vegetal origin in form of aerosol of submicron particles, obtained using said generator - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to pneumatic generators of liquid aerosol submicron drug particles and composition of said agent for use in medicine for treating nasopharyngeal diseases, bronchi and lungs. Generator includes following elements. Axially symmetric body of spray chamber with mouthpiece, union with outlet hole in end in form of nozzle for supply of air from compressor, located in spraying chamber body coaxially with it. Cap with outlet hole in end in form of nozzle has longitudinal projections-partitions on inner channel surface and it is located on union with formation of dispersing nozzle and radial vertical channels, connected with cap outlet hole on one side and with inner volume of spraying chamber at its bottom on the other side. Unit of sprayed substance preset temperature maintenance with thermal relay and baffle plate for removal of aerosol coarse particles. Baffle plate for removal of aerosol coarse particles is installed in body of spraying chamber and is made in form of horizontal tube, in cavity of which through hole in side wall cap end passes, attached with detachable elements with edges of hole of said tube for adjusting of gap between cap and tube inner side surface of baffle plate. Agent, based on aqueous solution of powdery mixture of flavonoids of dihydroquercetin and arabinogalactan of siberian larch or Gmelin larch in ratio from 1:5 to 1:20 is prepared in form of particles with submicron median diameter of 358–670 nm in aerosol liquid using said generator of particles. Quantitative content of components is as follows, wt% powdered mixture of flavonoids of dihydroquercetin and arabinogalactan of siberian larch or Gmelin larch in ratio from 1:5 to 1:20 – 0.05–5.0; water – the rest up to 100 %.

EFFECT: inventions provide higher dispersion of obtained liquid aerosol drug to submicron particle size, their deep penetration into respiratory tract of human body and higher pharmacological activity of components of agent.

3 cl, 4 dwg, 3 ex, 4 tbl

Description

The invention relates to pneumatic generators of liquid aerosol submicron particles of a drug and the composition of the specified funds, ensuring its deep penetration into the respiratory tract of the human body, and can be used in medicine for the treatment of diseases of the nasopharynx, bronchi and lungs.

Known pneumatic nebulizer of a medicinal product, comprising a housing having a chamber for containing aerosol; an air outlet in communication with said chamber to provide aerosol exit from the chamber; a liquid outlet located in said chamber; a compressed gas outlet located in said chamber adjacent to said liquid outlet; a deflecting element located in said chamber in a fixed position relative to said compressed gas outlet and said liquid outlet, with the possibility of deflecting the compressed gas from said gas outlet through a liquid outlet to form an aerosol, and a protective means located in said chamber, with the possibility of movement in accordance with the patient’s breathing (RF patent No. 2188041, IPC A61M 11/06, publ. 08/27/2002). This device does not have the ability to control the temperature of the dispersible drug solution.

Known aerosol inhaler (see ed. Certificate of the USSR No. 1321422, IPC A61M 11/00, publ. 07/07/1987), containing a source of compressed gas, an aerosol control system and an atomizer with a nozzle and a heater. This inhaler is intended for inhalation therapy.

The disadvantages of the above inventions are the low dispersion of the resulting aerosol and the inability to control this dispersion.

The closest analogue (prototype of an aerosol generator) is a pneumatic generator of liquid aerosol particles, including an axisymmetric housing of the spray chamber with a mouthpiece, a nozzle with an outlet in the end in the form of a nozzle for supplying air from the compressor, located in the housing of the spray chamber coaxially last, a cap with an outlet in the end face in the form of a nozzle having longitudinal projections-partitions on the surface of the internal channel and located on the nozzle with the formation of a dispersing nozzle and radially arranged vertical channels communicating on the one hand with the outlet of the cap, and on the other hand, with the internal volume of the spray chamber at its bottom, a unit for maintaining the set temperature of the sprayed material from the thermal relay, and a breaker element for removing large aerosol particles (RF patent No. 2355432, IPC A61M 15/00, published on 05/20/2009).

The disadvantages of the above prototype are insufficiently stable maintenance of the desired temperature of the dispersible solution of the drug and low dispersion of the resulting aerosol, as well as the inability to control the specified dispersion.

The effectiveness of the biological action of substances largely depends on their solubility in aqueous solutions. This parameter is determined by the "hydrophilicity" of the molecules. The physical meaning of this concept lies in the fact that a hydrophilic molecule has the ability to form hydrogen bonds with water molecules, forming a solvate shell, and this ensures the thermodynamic stabilization of solutions. If the molecule is lipophilic, hydrogen bonds are not formed and dissolution in water is not thermodynamically favorable.

As you know, many of the biologically active substances, including medicinal, synthetic and natural origin, have low water solubility and are thus lipophilic.

Methods for increasing water solubility of poorly soluble drug substances based on the formation of intermolecular complexes with cyclodextrins, most often with β-cyclodextrin, are widely used. Molecules of cyclodextrins have a toroidal shape, and its internal cavity is hydrophobic. Water-soluble intermolecular complexes of lipophilic organic compounds are formed in solution due to the intercalation of their molecules in this cavity. The known complexes of β-cyclodextrin with non-steroidal anti-inflammatory drugs (paracetamol, ibuprofen, ketoprofen, flufenamic and mefenamic acids, etc.), steroids, prostaglandins and prostacyclins, barbiturates, sulfonamides, cardiac glycosides and other drugs [ Szejtli, Industrial Applications of cyclod extrins. - in Inclusion Compounds, V. 3. ed. Atwood J. L., Davies J. E., Mcnicob D. D., Academic Press, N-Y., 1984, P 331-390].

Known Pharmaceutical preparations containing cyclodextrin derivatives (US Patent No. 4727064). It describes the preparation and use of water-soluble inclusion complexes of sparingly soluble lipophilic drugs - sex hormones with cyclodextrin derivatives. The complexes are obtained in solution, followed by drying to a solid dry material. The patent provides examples of increasing the solubility of a number of biologically active substances due to complexation with cyclodextrins.

Another analogue of the invention is a study [Shan-Yang Lin, Chun-Sen Lee, J. Inclus. Phenom. Mol. Recogn. Chem., 7, 477-485 (1989)], devoted to the study of inclusion complexes of acetaminophen (paracetamol) and alpha and beta cyclodextrins, as well as microcrystalline cellulose, obtained by processing mixtures of components in a ceramic ball mill. The authors note a decrease in the degree of crystallinity of substances with increasing processing time, which is associated with the formation of intermolecular complexes.

The closest analogue (prototype drug) is a composition based on a powder mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or Gmelin larch in a ratio of 1: 5 to 1:20, obtained by impact-abrasion with a mechanical energy of at least 20-40 J / g for 4 hours (RF patent No. 2421215, IPC АКК 31/15, publ. 06/20/2011).

However, these analogues and prototype have insufficient pharmacological activity of medicinal substances of plant origin - flavonoids and carotenoids and a high dose of the drug substance necessary to achieve the basic pharmacological action, which enhances the side effects of drugs.

The technical result of the claimed group of inventions is to increase the dispersion of the obtained liquid aerosol of the drug to submicron particle size due to the improved design of the aerosol generator and increase the pharmacological activity of medicinal substances of plant origin - a mixture of flavonoids dihydroquercetin and arabinogalactan obtained in the form of submicron aerosol particles, which reduce the dose of the drug substances necessary to achieve basic armakologicheskogo action and reduce its side effects on the body.

The specified technical result is achieved in that in a pneumatic generator of liquid aerosol submicron particles, including an axisymmetric housing of the spray chamber with a mouthpiece, a nozzle with an outlet in the end in the form of a nozzle for supplying air from the compressor, located in the housing of the spray chamber coaxially last, a cap with an outlet in the end face in the form of a nozzle having longitudinal projections-partitions on the surface of the internal channel and located on the nozzle with the formation of a dispersing nozzle and vertically located vertical channels communicating on one side with the cap outlet and on the other hand with the internal volume of the spray chamber at its bottom, a unit for maintaining the set temperature of the sprayed material from the thermal relay, and a chipper for removing large aerosol particles, according to the invention, a chipper for removing large aerosol particles are installed in the housing of the spray chamber and are made in the form of a horizontally located tube, into the cavity of which an end cap is passed through an opening in the side wall ka kinematically connected by detachable elements with the edges of the hole of the specified tube to regulate the gap between the cap and the inner side surface of the chipper tube. The detachable elements for adjusting the gap between the cap and the inner side surface of the chipper tube are made in the form of a threaded connection. The unit for maintaining the set temperature of the sprayed substance is made in the form of a thermostatic chamber with a liquid carrier, the housing of which is located around the housing of the spray chamber.

The presence of detachable elements ensuring the connection of the cap with the chipper tube allows you to adjust the gap between the cap and the inner side surface of the chipper tube, which allows you to adjust the dispersion of the aerosol particles of the drug. The chipper tube, located horizontally in the spray chamber, provides submicron particles (less than 0.5 microns), the deposition and removal of part of medium-sized particles from 0.67 to 1 microns and the removal of all large particles of more than 1 micron.

The specified technical result is also achieved by the fact that in a tool based on an aqueous solution of hydrophobic compounds of plant origin, in which it contains a powdery mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or Gmelin larch in a ratio of 1: 5 to 1:20, according to the invention, the preparation is prepared in the form of submicron particles having a median diameter of 358 to 670 nm in aerosol liquid form using a pneumatic generator of liquid aerosol parts . Formula according to claim 1, with the following quantitative content of components (wt.%):

powdery mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or larch Gmelin in a ratio of 1: 5 to 1:20 0.05-5.0 water - the rest up to 100%

In FIG. Figure 1 shows a diagram (sectional view) of a pneumatic generator of liquid aerosol submicron particles. In FIG. 2 shows a spray and a thermostatically controlled chamber with a longitudinal section of a chipper tube. In FIG. 3 shows a spray and a thermostatically controlled chamber with a transverse section of the chipper tube. In FIG. 4 shows a section AA of a cap with a fitting in FIG. 2.

The pneumatic generator of liquid aerosol submicron particles includes an axisymmetric housing 1 of the spray chamber 2 with a mouthpiece 3, a nozzle 4 with an outlet 5 at the end in the form of a nozzle for supplying air from the compressor 6. In the housing 1 of the spray chamber 2, a cap 7 with an outlet 8 is located coaxially with the latter in the end face in the form of a nozzle having longitudinal projections-baffles on the surface of the internal channel 9. The cap 7 is mounted on the fitting 4 with the formation of a dispersing nozzle and radially located vertical channels 10, communicating on the upper side with the outlet 8 of the cap 7, and on the lower side, with the internal volume of the spray chamber 2 at its bottom.

In the housing 1 of the spray chamber 2, a baffle is installed to remove large aerosol particles, made in the form of a horizontally located tube 11, into the cavity of which a cap 7 is passed through a hole in the side wall, kinematically connected by detachable elements 12 with the edges of the hole of the specified tube 11 to adjust the gap between cap 7 and the inner side surface of the tube 11 of the fender. The detachable elements 12 for adjusting the gap between the cap 7 and the inner side surface of the tube 11 of the fender are made in the form of a threaded connection.

The device is equipped with a unit for maintaining a predetermined temperature of the sprayed substance, including a thermostatically controlled chamber 13 with a liquid carrier, a housing 14 of which is located around the housing 1 of the spray chamber 2, a thermal relay 15 connected to a power supply unit 16, a heating element 17, and a temperature sensor 18.

The inventive generator operates as follows. A dispersible drug suspension is poured into the spray chamber 2. By means of a thermal relay 15, a predetermined temperature of the liquid carrier is set in the thermostatically controlled chamber 13. The necessary clearance is established between the inner surface of the chimney tube 11 and the outlet 8 of the cap 7. Next, the compressor 6 is turned on and the drug is ejected through the channels 10 through the air flow and sprayed . The resulting aerosol is discharged from the generator through the mouthpiece 3 in the housing 1. The dispersing nozzle is a channel 10 through which the sprayed suspension of the drug from the chamber 2 is sucked due to the created discharge by a stream of clean air supplied from the outlet 5 of the nozzle 4 to the axial exit 8 cap 7. At a section of the hole 8 (nozzle) of cap 7, the suspension of the drug is dispersed, and the flow of the resulting aerosol strikes the inner wall of the rebound tube 11 ika. Due to the small distance between the cut of the hole 8 (nozzle) and the inner surface of the chimney tube 11, it is possible to remove from the aerosol stream a part of the particles larger than 0.67 μm in diameter and almost all of the particle larger than 1 μm. Particles exceeding the required size are returned to the spray chamber with the drug solution.

The claimed agent is based on the phenomenon of increasing the solubility of poorly soluble medicinal substances discovered by the authors due to the formation of their water-soluble complexes with the natural plant polysaccharide arabinogalactan and the method of their preparation in the solid phase by mechanical processing of their powder mixtures with intense mechanical stresses.

Use for complexation of drugs polysaccharide arabinogalactan. Arabinogalactan is a polysaccharide metabolite of endemic Siberian forest flora of Siberian larch (Larix sibirica) and Gmelin larch (Larix Gmelinii) and is easily isolated from the wood of these trees. The content of arabinogalactan is up to 15% by weight of dry wood. It must be emphasized that both species of larch are the main components of the forests of Eastern Siberia. Isolation and purification of arabinogalactan is carried out according to a simple technology. To isolate arabinogalactan can be used waste logging, sawmilling, pulp and paper industry. Thus, arabinogalactan in its availability has no competitors among natural and biosynthetic polysaccharides [RF Patent, Method for the production of high-purity arabinogalactan, RF 2143437., Е.N. Medvedev, V.A. Babkin, L.A. Ostroukhova, Larch arabinogalactan - properties and development prospects (review), Chemistry of Plant Raw Materials, 1 (2003), p. 27-37. S.A. Kuznetsova].

Chemically, arabinogalactan is a comb polysaccharide with m.m. 9-18 kD. The main chain consists of galactose units, the side chains of arabinose and galactose units. In our opinion, this structural feature can contribute to the formation of strong intermolecular complexes of drugs, the molecules of which are most likely bound by intermolecular hydrogen bonds in the space formed by the side chains. Given the conformational mobility of arabinogalactan macromolecules, this space can vary, contributing to the formation of intermolecular complexes with a wide range of substances. In addition, it is possible to form complexes of different stoichiometric composition, when one molecule of arabinogalactan can bind to several molecules of other organic compounds - drugs, allowing you to change the ratio of these components over a wide range. This is the advantage of arabinogalactan as a complexing agent compared to cyclodextrins commonly used for this purpose. The use of complexes is foreseen, mainly containing 5-20% by weight of substances of drugs and 80-95% by weight of purified arabinogalactan.

A method of obtaining a water-soluble drug composition (of the claimed agent) involves mixing the complexing agent of arabinogalactan with the original powdered drug substance of dihydroquercetin flavonoids, which is subjected to mechanical processing.

Preferably, the machining is carried out by impact abrasion.

Preferably, the water-poorly soluble drug substance and arabinogalactan are taken in a ratio of 1: 5 to 1:20 by weight, respectively.

Preferably, the mixture of a slightly soluble in water drug substance of dihydroquercetin and arabinogalactan is subjected to mechanical shock treatment until the crystalline phase of the drug substance disappears.

In our invention, to obtain complexes, we used the mechanochemical approach, which consists in treating a mixture of solid components with intense mechanical stresses - pressure and shear deformations realized in extruders, as well as mainly in various types of mills that perform impact-abrasive effects on substances [Dushkin A.V. Possibilities of the mechanochemical technology of organic synthesis and the production of new materials, Chemistry for Sustainable Development, 12 (2004), p. 251-274].

A mixture of dihydroquercetin and arabinogalactan, taken predominantly in ratios from 1: 5 to 1:20 by weight, is machined, preferably in ball mills, in particular planetary mills. However, for machining, it is also possible to use devices that realize the long-term (non-pulsed) action of high pressure and shear deformation - extruders. During the mechanical treatment, the molecules of drugs are dispersed from its “initial” crystalline state into an excess of the solid matrix of arabinogalactan, thereby forming a solid solution, which is a disordered solid phase, in which the dihydroquercetin and arabinogalactan molecules experience non-covalent nonionic interactions - similar to the above interactions upon complex formation in solution. During the dissolution of this solid dispersion, the release of the drug occurs in the form of its complexes.

As apparatuses for machining, extruders can be used in which the mechanical action is extended in time, as well as mainly ball roll, planetary, vibration, vibrocentrifugal, etc. mills with shock abrasion. It is possible to use grinding bodies other than balls, for example rods. The process scales from ball laboratory mills with a load of several grams to flow vibrocentrifugal mills with a capacity of up to 100 kg / h or more [Internet site of Novits CJSC http://www.novic-mill.ru]. There are no special requirements for controlling the humidity of the premises, since the substances are processed in the sealed internal volume of the mills. In all cases, the process is carried out in virtually one stage, does not require expensive equipment and is easy to implement. The specific parameters of technological processes depend on the physicochemical and physico-mechanical properties of the components used.

The following are examples of the compositions of the claimed funds, which are prepared in the form of submicron particles having a median diameter of 358 to 670 nm, in aerosol liquid form using the inventive pneumatic generator of submicron particles, wt. %:

Example 1

powdery mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or larch Gmelin in a ratio of 1: 5 to 1:20 0.05 water - the rest up to 100%

Example 2

powdery mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or larch Gmelin in a ratio of 1: 5 to 1:20 0.9 water - the rest up to 100%

Example 3

powdery mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or larch Gmelin in a ratio of 1: 5 to 1:20 5,0 water - the rest up to 100%

The effectiveness of the method is demonstrated by the formation of water-soluble complexes of arabinogalactan with a slightly soluble substance of dihydroquercetin in water (see example 4).

Pharmacological tests of the obtained complexes in laboratory animals (mice) showed that several times a smaller dose of the drug was required to obtain the same specific pharmacological action (sedative, anti-inflammatory effect, etc.) in comparison with the initial agent.

Example 4. The technology of obtaining the claimed funds in the form of an aqueous solution of a complex of dihydroquercetin and arabinogalactan.

Take 0.25 g of dihydroquercetin (DHA) and 2.5 g of arabinogalactan (weight ratio 1:10) are processed in an AGO-2 planetary centrifugal mill for 10 minutes with an acceleration of grinding media of 60 g. The powder is discharged and analyzed. In the untreated mixture, X-ray diffraction reflections characteristic of the crystalline phase of dihydroquercetin and a melting phase transition disappearing after mechanical treatment. As a result of the mechanical treatment of the mixture, characteristic traces of the crystalline phase of dihydroquercetin disappear - it is molecularly dispersed into an excess of the solid phase of arabinogalactan. Similar changes occur in a mixture of 0.125 g of dihydroquercetin with 2.5 g of arabinogalactan (weight ratio 1:20). The increase in water solubility / lipophilicity of dihydroquercetin (DHA) due to the formation of its lipophilic complexes with arabinogalactan is shown in table 1.

Example 5. The technology of obtaining the claimed funds in aerosol form.

The dispersing device is represented by the inventive pneumatic submicron aerosol generator with a thermostatic nebulizer nozzle (Fig. 1-5). Pneumatic parameters: air flow - 4 ± 0.5 l / min, working pressure - 1.2 ± 0.1 kgf / cm ² . The nebulizer capacity is thermostated at 30 ° C to ensure better solubility of the nanocomposite and to improve the qualitative and quantitative characteristics of the resulting aerosol.

Dispersion of the agent in the form of aqueous solutions of the nanocomposite of dihydroquercin and arabinogalactan (0.05%; 0.1%; 0.5%; 1% solutions) provides a volumetric flow rate of 5 to 10 ml / hour, depending on the concentration of the drug. The median particle size depending on the concentration of the nanocomposite is in the range from 358 to 670 nm. The inventive tool does not lose its properties during dispersion and the reverse process of transferring the aerosol phase into a liquid. Drug solutions can be stored for 24 hours at low positive and negative temperatures without losing their physico-chemical properties.

Example 6. Evaluation of the effect of inhalation administration of the claimed drug on the hematological parameters of blood and the morphological structure of lung tissue in experimental animals with the syndrome of "shock lung".

The experiments were carried out on 31 JCR mice weighing 23-25 g. The animals were kept on a standard diet of vivarium, with free access to water and food, in accordance with the rules adopted by the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes.

To determine the effect of inhaled administration of the drug on hematological parameters in experimental animals with "shock lung" syndrome, the pathological process was induced by aerosol administration of endotoxin E. Coli 0127: B8 (received dose - 5 mg / kg) in combination with preliminary intramuscular injection of lipopolysaccharide (received dose - 10 mg / kg) to provide a bonus effect.

Mice were divided into three main groups: the first - intact animals; the second - animals with induced "shock lung" syndrome; the third - animals with induced "shock lung" syndrome and inhaled administration of the inventive drug for six hours (received dose of 17.3 mg / kg). At the end of the experiment, animals were sampled from the retroorbital sinus in pre-heparinized tubes. A blood test was performed on a MicroCC-20Plus instrument. Animals were slaughtered by cervical dislocation for subsequent extraction of the respiratory system. Lungs were fixed in 10% neutral formalin, followed by standard histological treatment on a MICROM Karl Zeiss Germany complex, including filling in paraffin blocks, obtaining sections of 3-5 μm and staining with hematoxylin and eosin. Assessment of morphological changes was carried out by a semi-quantitative method according to Smiths. When the microscope was increased to 1000 with immersion per 1000 cells (10-12 fields of view), neutrophils were counted in the alveolar septa.

The remaining parts of the lungs were weighed and placed in a thermostat at 40 ° C. After 24 hours, the dried samples were weighed repeatedly. The moisture content of lung tissue was determined by the ratio of the masses of wet and dry preparations.

The results of the study. Mortality among animals receiving inhalation of the claimed drug was 2 times lower compared with the control group (table. 2). The moisture content of lung tissue (Table 3) in the group with shock-induced syndrome and inhaled administration of the drug was significantly lower relative to the group that did not receive the drug. Differences were found in the degree of interstitial inflammation, the number of hemorrhages, and the concentration of neutrophils (Table 4). The hemoglobin concentration and hematocrit in the third group of animals are significantly higher relative to animals from the second group.

* p <0.05 - relative to the second group.

Thus, the technical result of the claimed group of inventions is achieved by increasing the dispersion of the obtained liquid aerosol of the drug to particles of submicron size due to the improved design of the aerosol generator and increasing the pharmacological activity of medicinal substances of plant origin - a mixture of flavonoids dihydroquercetin and arabinogalactan obtained in the form of submicron aerosol particles, which provide reduction in the dose of the drug necessary for dos reduction of the basic pharmacological action, and a decrease in its side effect on the body.

Pharmacological tests of the obtained complexes in laboratory animals (mice) showed that several times a smaller dose of the drug was required to obtain the same specific pharmacological action (sedative, anti-inflammatory effect, etc.) in comparison with the initial agent.

Claims (4)

1. Pneumatic generator of liquid aerosol particles, including an axisymmetric housing of the spray chamber with a mouthpiece, a fitting with an outlet in the end in the form of a nozzle for supplying air from the compressor, located in the housing of the spray chamber coaxially last, a cap with an outlet in the end in the form of a nozzle, having on the surface of the inner channel, longitudinal protrusions-baffles and located on the fitting with the formation of a dispersing nozzle and radially arranged vertical channels communicating with one rons with an outlet opening of the cap, and on the other hand, with the internal volume of the spray chamber at its bottom, a unit for maintaining the set temperature of the sprayed substance with a thermal relay, and a chipper for removing large aerosol particles, characterized in that the chipper for removing large aerosol particles is installed in the spray housing chamber and is made in the form of a horizontally located tube, into the cavity of which a cap end is passed through a hole in its side wall, kinematically connected by detachable elements to the edges of the hole said tube for regulating the gap between the cap and the inner side surface of the chipper tube, and the unit for maintaining the set temperature of the sprayed substance is made in the form of a thermostatic chamber with a liquid carrier, the body of which is located around the body of the spray chamber. 2. The pneumatic generator of liquid aerosol particles according to claim 1, characterized in that the detachable elements for regulating the gap between the cap and the inner side surface of the chimney tube are made in the form of a threaded connection. 3. A tool based on an aqueous solution of hydrophobic compounds of plant origin, in which it contains a powdery mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or Gmelin larch in a ratio of 1: 5 to 1:20, characterized in that the tool is prepared in the form of particles, having a submicron median diameter of 358 to 670 nm, in aerosol liquid form using a pneumatic generator of liquid aerosol particles according to claim 1, with the following quantitative content Ponents (wt.%): powdery mixture of flavonoids dihydroquercetin and arabinogalactan from Siberian larch or larch Gmelin in a ratio of 1: 5 to 1:20 0.05-5.0 water - the rest up to 100%

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