Emulsion drug for the prevention of respiratory viral infections |
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IPC classes for russian patent Emulsion drug for the prevention of respiratory viral infections (RU 2189231):
    
![2-amino-4-acetylthiazole[5,4-b]indole, protect the body from the effects of hypoxia and toxic edema](http://img.russianpatents.com/img_data/49/495162-s.gif) 2-amino-4-acetylthiazole[5,4-b]indole, protect the body from the effects of hypoxia and toxic edema / 2188824
The invention relates to the field of chemistry and pharmacology of compounds that belong to the series of condensed heterocycles-thiazolidone, namely 2-amino-4-acetylthiazole[5,4-b]indole of formula 1, having antihypoxic activity at the level of the reference antihypoxic drug and actively protecting from toxic edema
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 The use of the extract of non-photosynthetic filamentous bacteria-containing composition / 2188029
The invention relates to the field of medicine and for the application of at least one extract of non-photosynthetic filamentous bacteria as an antagonist of substance P for the treatment of diseases associated with excessive synthesis and/or release of substance P
 New anti-allergic anti-inflammatory composition and method of reception / 2188007
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 Way rehabilitation carriers of staphylococcus aureus / 2187299
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The invention relates to medicine, in particular to therapy, may be used for the treatment of chronic pharyngitis against the background of a dysbacteriosis of intestines
 Acylaminocinnamic derivatives, processes for their preparation and pharmaceutical composition based on them / 2185375
The invention relates to acylaminocinnamic derivative of the formula (I), where R denotes phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, R1is hydrogen, alkyl, R2is hydrogen, alkyl or phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, R3is phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, or represents naphthyl, lH-indol-3-yl or 1-alcheringa-3-yl, R4' and R4"is hydrogen, alkyl, and one of the radicals R4' and R4"is hydrogen, and R5- cycloalkyl, D-azacycloheptan-2-he-3-yl or L-azacycloheptan-2-he-3-yl, or its salt
For the treatment of patients with chronic bronchitis / 2184560
The invention relates to medicine, namely to phytotherapeutic medication of patients with chronic bronchitis
 The method of dissolving residual stones choledochus / 2189178
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 Tool for use in psychotherapy of psychosis, psychological prevention and consumer mental hygiene, rehabilitation and prevention of relapse in patients with a history of psychosis / 2188663
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 The method of obtaining biologically active composition having anti-inflammatory activity / 2188662
The invention relates to cosmetic and medical industries and relates to the application of herbal extracts as anti-inflammatory agents
Treatment of placental insufficiency / 2188661
The invention relates to medicine, namely to obstetrics, and can be used for the treatment of placental insufficiency
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The invention relates to medicine, dermatology
 Tool and method for disinfection of hatcheries and commercial eggs / 2188542
The invention relates to veterinary
 The phytocomplex with antioxidant activity, and method thereof / 2188031
The invention relates to medicine
 Treatment of selenium deficiency in children with metabolic syndrome / 2188030
The invention relates to medicine, namely to Pediatrics
 The method of determining the content of components in the collection microscopic method / 2187803
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The invention relates to medicine, specifically to pharmacology
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(57) Abstract: The invention relates to medicine, namely to drugs in aerosol form on the basis of natural polyisoprenoid. Emulsion drug for the prevention of respiratory viral infections includes polyisoprenoid, nonionic surfactant and water-based. As polyisoprenoid use natural polyprenols, in particular polyprenols wood greenery of Siberian fir (Abies sibirica), and the finished emulsion form of the drug is an aqueous microemulsion with turbidimetric parameter P, predominantly not less than 2.0, the next time the percentage of components, wt.%: polyisoprenoid fir of 0.01 to 5.0; nonionic surfactant is 0.05-25; water based and the rest to 100%. The technical result is the strengthening of preventive protection against respiratory viral infections. 2 C.p. f-crystals, 3 tables. The invention relates to medicine, namely to drugs in aerosol form on the basis of natural polyisoprenoid for the prevention of respiratory viral infections. Polyisoprenoid represent a large group of widely spread in nature regularly postroennaja the polyprenols, the molecular structure of which is expressed by the General formula (I), and their derivatives - doliolum (II) with a broad spectrum of biological activity [1], including together with immunomodulating and protective bacterial and viral infections (colibacteriosis and Sendai infection) [1-3]. Polyprenols are more common in plants, and gymnosperms characteristic polyprenols with m = 2 (Betulaceae), and angiosperms are more characteristic of compounds with m = 3 (picarray). Dihydrobromide polyprenols - dolichol distributed mainly in animal organisms, where perform important regulatory functions. Currently, these groups of substances are considered as a new class of low-molecular bioregulators (especially important in the biosynthesis of polysaccharides and glycoproteins). < / BR>< / BR> Dolichol have a higher biological activity and are preferred for development of new therapeutic and preventive drugs. However, the concentration of dolichols in animal tissues is very low (for example, from 10 kg pork liver can provide about 0.6 g of dolichols). Moreover, currently, there are great difficulties in preparative getting dolichols fully synthetic means. This is the new drug. However, a mixture of natural polyprenols can be extracted from the green parts of many plants (e.g. leaves of the Ginkgo biloba /raw materials for therapeutic drug BILOBIL/ late autumn contain up to 2% of polyprenols). Other conifers (few Pinaceae family) also contain polyprenols in considerable quantity, and the composition of polyprenols (m = 2, n = 12 - 19, predominantly n = 13, 14) corresponds to the composition of natural dolichols (m = 2, n = 12 - 19, predominantly n = 13-15) [1,4]. In the scientific and patent literature has repeatedly stressed the ability of different polyisoprenoid (including various polyprenols, dolichols and their esters and ethers) to normalize immune function of the body and increase its resistance to infections[1 - 3, 6, 8 - 11]. The mechanism of the protective action of polyisoprenoid and their derivatives are generally attributed to their ability to stimulate the generation of neutrophils and activated macrophages RES[1, 2, 8, 10]. Known pharmaceutical preparations on the basis of various polyisoprenoid (tablets, capsules, powders), external (creams and leniency) for injection, intranasal or oral administration. In these pharmaceutical compositions is the R immunodeficiency, and in combination with antibiotics for the treatment of infectious diseases marked by the use of different polyisoprenoid and their derivatives (including dihydropyridine and their ethers and esters) [1-3, 6, 8 - 11]. However, in the known sources of information there is no information about the use of data structures and forms of drugs for the prevention of respiratory viral infections. This publication is unknown, which immunostimulirutuyu and antiviral activity (including polyprenols fir) inhalation use in aerosol form can be significantly increased through the use of emulsifiers and solubilization and maintenance of the required characteristics of the emulsions (mostly getting microemulsions). The closest analogue (prototype) to the proposed technical solution is emulsion composition for injection (intramuscular) applications containing synthetic polyphenylsulfone and lecithin as an emulsifier. The drug has activity as a preventive tool in case of E. coli infection in white mice [11]. The disadvantages of this method include the need to use high doses of the active of exectives injection applications polyisoprenoid for respiratory infections [3]. The task of the invention is to create a drug that would strengthen its preventive action by increasing the efficiency of delivery and utilization of polyisoprenoid in vivo by constructing emulsion compositions of polyisoprenoid with the required physico-chemical characteristics suitable for use in aerosol form. This task is solved in that the emulsion drug for the prevention of respiratory viral infections, including polyisoprenoid, nonionic surfactant and water-based, according to the invention as polyisoprenoid use natural polyprenols, in particular polyprenols of Siberian fir (Abies sibirica), and the finished emulsion form of the drug is an aqueous microemulsion with turbidimetric parameter P, predominantly not less than 2.0, the next percentage, wt. %: Polyprenols fir is 0.01 to 5.0 Nonionic surfactant is 0.05-25,0 Water based - the Rest is up to 100% As the nonionic surface-active substances are used esters of fatty acids with polyethylene glycol, or apiradee castor oil, or higher fatty alcohols (C16-C18). As a water based use of water-salt or aqueous-alcoholic compositions. In the development of pharmaceuticals (including on the basis of various polyisoprenoid) know the use of emulsifiers to improve the biological activity of drugs. However, they are used for the preparation of an injectable steroid creams and liniments[6, 8, 10, 11]. A feature of this invention is inhaled forms application polyisoprenoid (in aerosol form). The advantage of the proposed solution is the ability to significantly reduce the applied dose of the drug, as well as to provide selective activation of the immune system of the respiratory tract with the purpose of providing treatment-and-prophylactic actions against respiratory infections (especially influenza activity). Polyprenols of Siberian fir (Abies sibirica) were selected on the basis of resource availability and economic considerations (based on previously developed a low-cost method of their allocation from the needles [5]). General information about the technology used to prepare the inventive preparations micromole, described in [5]. Polyprenol (LTP) is chromatographically purified natural mixture of izoprenovogo described General formula (1), where m = 2; n = 6 to 16 (includes all members of the series, mainly with n = 12 and 13). To obtain pharmaceutical compositions of lipophilic polyprenols of Siberian fir (obtained by extraction of drugs needles) used methods: emulsification and solubilization. The quality of the emulsions for aerosol inhalation is determined (if all other conditions being equal) their dispersion, i.e. the size of the micelles dispersed phase, and the stability, i.e. the ability to exist for a long time, not esclavas. On aggregative stability of emulsions is most strongly influenced by the nature of the emulsifier and its content in the system. As emulsifiers can be applied to the different nature of matter: ionic and nonionic surfactants (surfactant) and high-molecular compounds. The solubility of drugs in water is an important condition for their preventive effect. In pharmaceutical technology the solubility of hydrophobic drugs is achieved by the use of complexing agents, solubilization and different leads to a rapid and complete absorption. In addition, some solubilization have the ability to enhance the pharmacological action of drugs that can reduce their dose. In pharmaceutical practice as often as soljubilizatory use nonionic surfactants, because they have several advantages: absolute stability in hard water, electoral solubilizers ability, relatively low toxicity, etc. To obtain pharmaceutical compositions of polyprenols as emulsifiers and solubilization used nonionic surfactants include Esters of fatty acids with polyethylene glycol, esters of fatty acids with polyhydric alcohols (sorbitol), or block copolymers of ethylene and propylene, or ethoxylated higher alcohols (C16-C18), or castor oil. Dispersion characteristics of the emulsions (able to affect the distribution of the particle fractions aerosol) was controlled by the turbidimetric method, recording the turbidity of the emulsion and/or turbidimetric parameter P [7] determined by turbidity spectra A() (in the wavelength range from 400 to 650 nm) interpolation formula LogA (a) = C-PLog(), where C is a constant. Turbidimetric parameter P is defined as the ratio oneyrichesky radius) can be quantified by theoretical calibration curve. In the case of emulsion particles having particle sizes of more than 500 nm, or polydisperse emulsions indicator R allows comparative analysis of emulsions, to control the reproducibility of the methods of preparation and study the changes in the properties of drugs during storage. Smaller values of R correspond to larger micelles of the emulsion. The dispersible emulsions (used for inhalation) and properties of aerosol characterized by the following parameters: the efficiency of transfer of the drug in aerosol fractional-dispersed composition of the aerosol and download the target faction when dispersion conditions simulating inhalation application. The dispersion of the emulsion was performed by ultrasonic aerosol inhaler "Vulcan-1 at an average power value of the emitter, the sample volume of 20 ml and a temperature of 37oC. To determine the mass concentration of aerosol and fractional-dispersed composition was performed isokinetic sampling flow spray directly at the output of the nebulizer on a four-stage cascade impactor and filter. Air flow 25 l/min controlled by a rotameter. To register the amount of spray used vodorosti (loading the target fraction) was used (taking into account the spectral characteristics) lipitorhistory fluorescent label - fixed. Selected aerosol washed with chisels, the impactor alkaline solution (NaOH in water at pH 11). The fluorescence intensity was measured on fluorimetry "PERKIN-ELMER - 1000". The following is a specific technology for microemulsions and examples of compositions in emulsion form. To ensure the effective delivery of the active substance in the respiratory tract and recycling polyisoprenoid in vivo (to enhance immunomodulatory and protective properties) drugs were prepared in one way or another, providing the formation of microemulsions with turbidimetric parameter P, predominantly, not less than 2.0. Example 1. Emulsion form of polyprenols prepared using the surfactant is Tween 80 (Serva). 1 g of polyprenol of pine needles mixed with 5.0 g of Tween 80 and thoroughly mixed components to obtain a visually homogeneous mixture (to speed up the process the mixture is warmed up in a water bath at a temperature of 60oC). Next, add with stirring distilled water (heated to 60o(C) to a total volume of 20 ml of the emulsion Obtained is R = 2,2 (particle size of about 0.5 microns). The percentage of components: weight. %: Polyprenols fir - 5 form of polyprenols are prepared on the basis of nonionic surfactants - Span 20 (Serva). 2 ml CPD needles in pentane (100 mg/ml) mixed with 1 g of Span 20 (diluted with 2 ml of ethanol, the mixture is dried on a rotary evaporator, diluted with 2 ml of ethanol, and then quickly injected into 50 ml of Hanks solution (heated to 50o(C) under vigorous stirring. The stable emulsion is R = 2,1. The percentage of components: weight. %: Polyprenols fir - 0,4 Nonionic surfactant Span 20 - 2,0 Water based (Hanks solution with 4% ethanol) Up to 100% Example 3. Emulsion form of polyprenols are prepared on the basis of non-ionic surfactant Span 20 (Srva). 2 ml CPD needles in pentane (100 mg/ml) mixed with 1 g of Span 20 (diluted with 2 ml ethanol). Next, the resulting mixture is quickly injected into 100 ml of Hanks solution (heated to 40 - 50o(C) under vigorous stirring. The stable emulsion is R = 2,4. The percentage of components: weight. %: Polyprenols fir - 0,2 Nonionic surfactant Span 20 - 1,0 Water based (Hanks solution with 2% ethanol) Up to 100% Example 4. Emulsion form of polyprenols are prepared on the basis of nonionic PLV - Tween 80 (Serva). 2 ml of polyprenols Hoyle, diluted with 2 ml of ethanol, and then quickly injected into 18 ml of distilled water under vigorous stirring. The stable emulsion is R = 2.0 and400=0,45. The percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactant Tween 80 - 5,0 Water based (10% aqueous solution of ethanol) Up to 100% Example 5. Emulsion form of polyprenols are prepared on the basis of non-ionic surfactant is Tween 80 (Serva). 2 ml of polyprenols needles in pentane (100 mg/ml) mixed with 1 g of Tween 80 (diluted with 2 ml ethanol). The resulting mixture was rapidly injected into 20 ml of Hanks solution (heated to 40o(C) under vigorous stirring. The stable emulsion is P = 2.44 and A400= 0,17 (turbidimetric diameter of the micelles is about 0.2 μm). The percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactant Tween 80 - 5,0 Water based (Hanks solution with 10% ethanol) Up to 100% Example 6. Emulsion form of polyprenols are prepared on the basis of non-ionic surfactant is Tween 80 (Serva). 2 ml of polyprenols needles in pentane (100 mg/ml) mixed with 1 g of Tween 80 (diluted with 2 ml ethanol). Poluchennaya. The stable emulsion is R = 3.5 and400= 0,1 (turbidimetric diameter of the micelles is less than 0.1 μm). The percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactant Twen 80 - 5,0 Water based (Hanks solution with 10% ethanol) Up to 100% Example 7. Emulsion form of polyprenols are prepared on the basis of nonionic surfactants - Twn 80 (Serva) and Span 20. 2 ml of polyprenols needles in pentane (100 mg/ml) mixed with 1 g Twen 80 and 0.2 g of Span 20 (dissolved in 2 ml ethanol). The resulting mixture (solution CPD and surfactant in ethanol) just enter in 18 ml of Hanks solution, heated to 50oWith vigorous stirring. The stable emulsion is P = 2,29. The percentage of components: weight. %: Polyprenols fir - 1,0 Surfactants:* Twen 80 - 5,0 Span 20 - 1,0 Water based (Hanks solution with 10% ethanol) Up to 100% Example 8. Emulsion form of polyprenols are prepared on the basis of a nonionic surfactant and emulsifier RO-35 (ethoxylated castor oil). 2 ml of polyprenols needles in pentane (100 mg/ml) mixed with 1 g of emulsifier RO-35 (ethoxylated castor oil), razvedenna 50o(C) under vigorous stirring. The obtained transparent microemulsion (P = 3,3) is the percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactant - emulsifier RO-35 - 5,0 Water based (Hanks solution with 10% ethanol) Up to 100% Example 9. Emulsion form of polyprenols are prepared on the basis of a nonionic surfactant and emulsifier "Emulgin B2" (based on ethoxylated higher alcohols WITH16-C18). 2 ml of polyprenols needles in pentane (100 mg/ml) mixed with 1 g of emulsifier "Emulgin B2", diluted with 2 ml of ethanol. The resulting mixture was slowly (dropwise) to introduce in 18 ml of Hanks solution (heated to 50o(C) under vigorous stirring. The obtained transparent ultrapulse (R = 3,5) is the percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactants of Emulgin B2 - 5,0 Water based (Hanks solution with 10% ethanol) Up to 100% Example 10. Emulsion form of polyprenols are prepared on the basis of the nonionic surfactant - emulsifier "Lutrol F68" (poloxamer based on block copolymers of ethylene and propylene). 2 ml of polyprenols needles in pentane (100 mg/ml) mixed with 1 g of emulsifier "Lutrol F68" (diluted with 2 ml ethanol). The mixture of races) under vigorous stirring. The obtained transparent microemulsion is the percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactants "Lutrol F68" - 5,0 Water based (Hanks solution with 10% ethanol) Up to 100% For comparison prepared liposomal emulsion and form of the drug close to the analogues [8 or 11] and used for injection. Example 11. Liposomal form of polyprenols are prepared on the basis of egg lecithin /company Roma (Russia)/. 2 ml of polyprenols needles in pentane (100 mg/ml) is mixed with 20 ml of lecithin in chloroform (100 mg/ml), and dried on a rotary evaporator in the form of a thin film, carefully emuleret in 20 ml of Hanks solution and dispersed by sonication on UZDN-1. The percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactants lecithin - 10,0 Water based (Hanks solution) Up to 100% The emulsion obtained has A400= 16,4; R = 0,59. The selected method of preparing lecithin preparations provides obtaining stable emulsions (not decaying storage). Within a few days in the emulsion is formed a small residue (easily dispersible by stirring). Feature of the emulsions of this type (drug-prototype) is their low resistance, which leads to the formation in the preparation of the fraction of large particles (>10 µm), visible under a light microscope (turbidimetric parameter P of the emulsion was changed during storage for several days from 0.56 to 0.24, which indicates the increase of the particles of the emulsion. If prolonged storage is observed the formation of large droplets of oil phase). The percentage of components: weight. %: Polyprenols fir - 1,0 Nonionic surfactant Span 20 - 5,0 Water based (Hanks solution with 10% ethanol) Up to 100% Example 13. Evaluation of Aerophysical performance drugs polyisoprenoid The preparations prepared in example 5 and examples 11 and 12 (controls), were used as samples for the study. Analysis by the methods of light and electron microscopy, as well as turbidimetry showed that the drug is prepared in accordance with example 11, is is prepared in accordance with example 12, consists of relatively large particles (up to 5 microns) and unstable. The drug is prepared in accordance with example 5 is a microemulsion, i.e. transparent (opalescent) product with the size of the micelles is about 0.2 μm (turbidimetric diameter). Thus, for aerosol experiments were selected 3 types of emulsions: polydisperse unstable emulsion R = 0,43 (example 12); a stable emulsion with submicron micelles R = 0,59 (example 11); a stable emulsion micelles of about 0.2 μm P = 2,44 (example 5). As the most appropriate characteristics of the dispersive ability of the pigment preparations were measured: effectiveness of transfer of the drug into an aerosol, fractional-dispersed composition of the aerosol, and load the target faction when dispersion conditions, relevant inhalant use. The experiments were conducted on an ultrasonic aerosol inhaler "Vulcan-1 at an average power value of the emitter, the sample volume of 20 ml and a temperature of 37oC. To determine the mass concentration of aerosol and fractional-dispersed composition was performed isokinetic sampling flow spray directly at the output of the nebulizer four is registracii number of aerosol used water-soluble fluorescent label - the fluorescein sodium (uranin). To determine the content of polyprenols in aerosol - lipitorhistory fluorescent label is fixed. Selected aerosol washed with chisels, the impactor alkaline solution (NaOH in water at pH 11). The fluorescence intensity was measured on fluorimetry "PERKIN-ELMER - 1000". Table 1 shows the results of experiments. Thus, the most effective means in the aerosol preparation, prepared in accordance with example 5. Judging by the results, further reducing the size of the micelles, as obtained for the preparation examples 6, 8-10 may only marginally increase the efficiency of translation in the aerosol. The use of emulsions with a P of less than 2.0 is not desirable due to the reduction of efficiency of transfer in aerosol Example 14. Evaluation of the preventive effects of polyisoprenoid when injecting their application to animals, airborne infected with influenza virus. Drugs are prepared in accordance with examples 5, 11 and 12, were used as samples for a comparative study of their preventive activity in experimental influenza infection in mice. In order to compare the biological activity of p. the rata according to examples 11 and 2 (similar to the prototype). Used the influenza virus strain A/Aichi/2/68 (H3N2), obtained from the Institute of Virology. D. I. Ivanovsky RAMS, past 12 passages in mice and two in developing chicken embryos (RCA). In the experiments used virusbulletin liquid obtained by cultivation of influenza virus in 9-11-day-old, RCA, with biological virus concentration of 108- 10950% embryo infectious doses (EID50) in 1 ml of Viral preparations prior research kept at a temperature of minus 12oC. The experiments were carried out on outbred mice of both sexes weighing 15-17 g (without antibodies to influenza virus A). Infected animals vaccinated by aerosol was carried out at a temperature of 20-24oC and relative humidity of 50-70% on installation, which consisted of: Spray vaccinated for suspensions type Collison [l2], operating at a gauge pressure of 0.8 - 1.0 ATM at the expense of air 16 l/min and a suspension of 0.1 ml/min and produces an aerosol with a median mass aerodynamic diameter of the particles of 1.1 μm ((g= 2,1). Aerosol dispenser, allowing you to gradually reduce the concentration of aerosol from 1:1 to 1:100. Small dynamic camera for 20 mice [13] with the P CLASS="ptx2"> Sampling equipment: DE=CTW, where Sa - biological virus concentration in the aerosol (lg50/l). The specificity of the death of the experimental animals was determined by hemagglutinin activity allantoine fluid taken from RCA inoculated with the suspension of the lung homogenate of dead animals. 50% airborne lethal dose (ALD50) was calculated according to the modified method of van der Varden [15], using the values of exposure dose. The drugs were injected animals intramuscularly with 0.1 ml of each drug (1000 mcg per head or p airborne way using 5 animals per dose. Table 2 shows the results of the evaluation of the preventive anti-influenza activity of drugs on the basis of polyprenols fir for injectable use in order to compare the protective activity of drugs with the prototype. Thus, reliable protective anti-influenza effect when injecting the application possessed only drug type coarse emulsion with the large sizes of the micelles (example 12). Producing drugs in example 5 (microemulsion) did not show any significant prophylactic activity. At the same time, the product from example 11, took an intermediate position on the sizes of the micelles, had no reliable preventive effect during influenza infection. Comparison with the prototype. In the prototype were analyzed by the protective action of drugs on the basis of polyphenylalanine when injecting drugs for infections caused by E. coli (in subcutaneous method of infection of animals). It is shown that the best medications at doses of 50 mg/kg of body weight was defended by up to 50-60% of animals dose approximately 6 LD50this infection. During influenza infection of the tested preparatoin them the product from example 12 was protected 40% of the animals from about the same aerosol dose of influenza virus with the introduction of the animal in an amount of about 60 mg/kg. At the same time, the drug 11 (stable lecithin by analogy with the prototype), which occupies an intermediate position on the sizes of the micelles, had no reliable preventive effect during influenza infection. Thus, as in the prototype, reliable protective anti-influenza effect when injecting the application possessed the drug type coarse emulsion with the large sizes of the micelles (example 12). Drugs CPD prepared with the use of nonionic surfactants in the form of a thin emulsion (example 5), do not show protective effect of intramuscular introduction. It is also fully consistent with the examples and results of the prototype indicates that was used as one of the options the non-ionic solubilizer, HCO-60 (providing microemulsions) has no protective effect in intramuscular. The preparations prepared according to examples 1-10, and the prototype show General patterns (depending on the characteristics of the emulsion) and similar in magnitude protective effect in intramuscular (in spite of the significant difference of disease caused by influenza virus and E. coli, and some differences in the composition amalgamations of polyphenylalanine prototype as well as the possibility of a quantitative comparison of biological activity of the preparative forms and prototype. Example 15. Evaluation of the preventive effects of BPD in the aerosol application on animals, airborne infected with influenza virus. Drugs are prepared in accordance with examples 5, 6 and 11, 12, were used as samples for a comparative study of their preventive activity at aerosol use against experimental influenza infection in mice. The product from example 11 - a stable emulsion with submicron micelles and mixed coarse particles. The product from example 12 - polydisperse unstable emulsion with particle sizes up to 10 microns. The product from example 5 - stable ultrapulse with micelles with a diameter of about 0.2 μm. The product from example 6 - stable ultrapulse with micelles with a diameter of less than 0.1 μm. Used the influenza virus strain A/Aichi/2/68 (H3N2), described in detail above. The experiments were carried out on outbred mice of both sexes weighing 15-17 g (without antibodies to influenza virus A). Treatment of mice with aerosols medications and influenza virus in addition to the equipment previously described, also the ultrasonic nebulizer "Vulcan-1" for the dispersion of drugs that ensure the flow of aerosol to 30 l/min and the flow rate of spray of the drug up to 3 ml/min using a nebulizer created aerosol, 85% by weight of which consisted of particles with MMAD from 0.8 to 2 μm. To determine the weight concentrations of aerosol used water-soluble fluorescent label is fluorescein sodium (uranin). The intensity of fluorescence uranine was measured atop= 520 nm (excitation at vasb= 472 nm). Aerosol dose of the drugs on the basis of polyprenols fir derived mice (DEp), was estimated by the formula DEp = CTW, where SP is the concentration of aerosol products in the camera (in ág/l) T - time exposure of animals (in minutes) W - the minute respiratory volume mouse (l/min) - 15 ml/min calculated according to the data given in the work of Guyton A. C. [16]. Assessment 50% bear airborne lethal doses (ULD50) and specificity of death of the animals was performed as described above. The effectiveness of the preventive action of drugs on the basis of polyprenols fir with influenza infection was determined by the share of the surviving animals. Processing mypa. Data on doses received by the animals, and their survival after infection with influenza virus are summarized in table 3. The greatest protective effect have the aerosols of the drug prepared in the form of a microemulsion (preparation 5): in 4 out of 8 studied diagrams of the drug survival of animals exceeded 75% (in one case it was 100%). Aerosol processing of animal product 6 was performed, varying the magnitude of the doses and regimens of the drug (the first treatment for 3-9 and/or the second treatment for 1-6 days before infection). In high doses, twice aerosol injection 6 (first - 4,56, and 9.6 µg/mouse and the second 6 μg/mouse) reliable protective effect in influenza infection is achieved by increasing the time interval between the second treatment drug and infection (up to 3 days). At the same time when using low doses of 1.4 and 1.4 μg/mouse in the first and second processing) preventive effect detected in infected animals within 1 day after the second treatment. Table 3 describes the protective effect of the drugs CPD in aerosol form in an aerosol infection of mice with influenza virus A/Aichi/2/68 (H3N2) in doses of 1 - 5 LD50. The use of coarse emulsions (preparations 11 and 12) also impractical due to the lower efficiency of translation in the aerosol and the increased consumption of the drug to obtain the desired therapeutic dose in the lungs. Thus, the preparations on the basis of polyprenols fir provide high protective activity when aerosol delivery method animals at the doses approximately 100 times smaller than with intramuscular injection, providing reliable preventive protection against respiratory viral infections. Sources of information 1. Grigoriev N. Ya, Moiseenko A. M. Physiological activity of polyisoprenoid (review of patent data) //Chem.-Pharm. zhurn., 1989, 2.-C. 144-155. 2. Araki, S., Kagaya, K., Kitoh, K., MIGA M., Fukazawa Y. Enhancement of resistance to Escherichia coli infection in mice by dihydroheptaprenol, a synthetic polyprenol derivatative, against Sendai virus infection in mice // Vaccine. - 1990. - Vol.8, N4. - R. 376-380. 4. Ibata, K., Mizuno, M., Tanaka Y., Kageyu A. Long-chain polyprenoles in the family of few Pinaceae. //Phytochemistry. 1984. Vol.23, No.4, pp.783-786. 5. Raldugin Century A. Polyprenols wood green fir: the use of liquefied carbon dioxide in the new way they are allocated. //Chemistry for sustainable development. 1997. N 5. C. 75-77. 6. Patent EP 0 239 729 B1 Koyama N., Ikeuhi T., Araki, S., Kioth K., Ida K. Polyprenol alcohol-containing injections and use thereof. 7. Slonim I. J. Determination of particle size on scattering. Formulas and nomograms for calculating the radius of the particle optical density and intensity of scattered light //Optics and spectroscopy. 1960. - volume 8. VOL.1. - S. 98-108. 8. US Potent (U.S. Patent 5280048), g - Dihydropolyprenyl alkohol derivatives and pharmaceutical composition containing a polyprenyl compound. 9. Patent 2005475 C1, MCI AND 61 TO 31/21 (RU). Antiviral agent. 10. Patent EP 0166436 A2. Use of dolichol or its ester in medicines. 11. Patent 4839389 (USA). Polyprenyl alcohol-containing injections. 12. Lapochka, K., Misnikov O. P., Rajewski K. K. Means and methods of studying microbial aerosols. HP: Medicine, 1985. 13. Sergeev, A. N. , Pyankova O. G., Bulychev L. E. etc. the Sensitivity of mice to influenza virus (A/AICHI/2/68) when airborne contamination //Matters. W. 15. Ashmarin I. P., Vorobiev A. A. Statistical techniques in microbiological research. HP: State. ed. the honey. lit., 1962. 16. Guyton A. C. Measurement of the respiratory volumes of laboratory animals // Am. J. Physiol. - 1947. - Vol. 150, N. 1. - P. 70-77. 1. Emulsion drug for the prevention of respiratory viral infections, including polyisoprenoid, nonionic surfactant and water-based, characterized in that as polyisoprenoid use natural polyprenols, in particular polyprenols wood greenery of Siberian fir (Abies sibirica), and the finished emulsion form of the drug is an aqueous microemulsion with turbidimetric parameter P, predominantly not less than 2.0, the next percentage, wt. %: Polyisoprenoid fir is 0.01 to 5.0 Nonionic surfactant is 0.05-25 Water based - the Rest is up to 100% 2. Emulsion preparation under item 1, characterized in that as a nonionic surface-active substances are used esters of fatty acids with polyethylene glycol, or esters of fatty acids with polyhydric alcohols (sorbitol), or block copolymers of ethylene and propylene, or ethoxylated castor oil, or higher Sosnovy use of water-salt or aqueous-alcoholic compositions.
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