Application of acetylsalicylic acid salt for treatment of viral infections
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions relates to medicine, namely to pharmacology and virology, and can be used for the prevention and treatment of viral infections, caused by RNA viruses with a negative chain, preferably flu viruses, first of all, viruses of H5 or H7 types. For this purpose a composition, containing a salt of o-acetylsalicylic acid with amino acid, selected from the group, including lysine, arginine, ornithine, diaminobutyric acid and a mixture of the said amino acids, is claimed. Also claimed is a method of applying an aerosol composition, which includes a salt of o-acetylsalicylic acid with natural or non-natural basic amino acid, a propellant and an optionally auxiliary substance and/or a carrier. The method involves aerogenic introduction of a physiologically active amount of the said aerosol composition to a person who is at risk of a viral infection or already infected by it, by inhalation through the nose or mouth.
EFFECT: inventions provide a possibility of efficient prevention and treatment of the said viral infections with good tolerability of the introduced preparation form and an absence of risk of asthma attack development.
12 cl, 12 dwg, 7 ex
The technical field to which the invention relates.
The present invention relates to a new use of a composition containing a salt of salicylic acid (ortho-oksibenzoynoy acid with a basic amino acid, for the preparation of pharmaceutical compositions.
The existing prior art and background of invention
The flu is still considered to be the most dangerous infectious diseases that can accept a pandemic. There is only a very limited number of medicines for causing disease pathogens, namely against influenza a viruses, a target which is only a virus. In this case there is a problem, which consists in the fact that relatively quickly may develop resistance. In addition, there is a danger that epidemically spreading among poultry avian influenza, caused by infection with influenza virus a type H5, can be transmitted to man. Thus, high risk, first of all, people in contact with infected poultry. In this regard, it should be noted that the growing number of reports of dead viruses of subtype H5N1 to the few allowed to use drugs, such as oseltamivir. Thus, the things is there is a great need for new and effective anti-influenza drugs, designed for both prevention and treatment of viral infections, and these medicines if possible, should not cause the development of resistance to them.
In document WO 2004/060360 A1 describes what acetylsalicylic acid can inhibit the transcription factor NF-kB in cells of the host resulting in the inhibition of the transmission signal of NF-kB, the necessary viral components remain in the cell nucleus and can no longer be integrated into the viral particles. The paper also described the airborne introduction of acetylsalicylic acid for the prevention or treatment of viral infections.
For example, in document DE 10202019 A1 describes salts of acetylsalicylic acid with a basic amino acid, where the composition is intended only for oral administration. In addition, the paper describes the use of these salts for the treatment of diseases of the rheumatoid type of arthritis, neuralgia, myalgia, migraine, ischemic heart disease, stroke, angina, myocardial infarction, when the operations associated with bypass surgery, when performing percutaneous catheter coronoplasty (RTSA), the implantation of stents, to stimulate the immune system of HIV patients for the prevention of tumors, to slow down the deterioration of cognitive abilities with ndrome dementia, for inhibiting the formation of gall stones and/or for the treatment of diabetic diseases. In addition, these salts are known under the trade name Aspisol®, already used as medicines for the treatment of asthma, hay fever, swelling of the mucous membrane of the nose or chronic infections of the respiratory tract, while the introduction is carried out not only orally, but also by injection. It should be noted that all of these diseases are not diseases directly associated with viral infections, which are caused by influenza viruses.
In principle, the use of pure acetylsalicylic acid as an antiviral agent, introduced in the form of an aerosol in the respiratory tract or lungs, very well tested on laboratory animals. However, in humans introduction by inhalation of pure acetylsalicylic acid may cause severe irritation of the respiratory tract. In addition, it was found that in some cases, the introduction by inhalation of acetylsalicylic acid can cause asthma attacks in some sensitive patients. In any case, the airborne introduction of acetylsalicylic acid as an anti-influenza drug should be contraindicated with asthma patients or individuals with risk has arisen is ovenia asthma.
The technical problem of the invention
Thus, the present invention was used to develop containing acetylsalicylic acid preparative form intended for the treatment of viral infections, which has a very good tolerance and, above all, reliably ensures the absence of risk of asthma attacks.
Summary of the invention and preferred embodiments of the invention
To solve this technical problem the invention proposed the use of a composition containing, in a physiologically effective dose of salts o-acetylsalicylic acid with naturally occurring or not naturally occurring amino acid, for the preparation of pharmaceutical compositions intended for the prevention or treatment of viral infections in humans or animals, especially mammals and birds. In the context of the invention, the term "viral infection" refers primarily to infections caused by naturally occurring viruses in wild type, but not to the infections caused by genetically modified viruses.
Among birds as targets for prevention or treatment is considered primarily to domestic birds such as chickens, geese, ducks, Pulaski, turkeys, INDU and, quail or doves, and songbirds.
When using such a salt, especially when airborne the introduction, does not irritate tissue, such as the mucous membranes of the respiratory tract, due to the fact that the active ingredient in the input preparative form is not acidic. This allows, first, to reliably prevent the occurrence of asthma attacks in asthma patients or individuals with the risk of asthma, and due to the absence of risks due to side effects, practically there are no obstacles to its widespread use as a therapeutic agent, and as a preventive measure, especially as specified preparative form already used even as a remedy against asthma. In addition, with the invention it has been unexpectedly found that the derivatization of acetylsalicylic acid practically does not reduce the inhibitory effect on viral replication; it has been unexpectedly found that it is even slightly increases.
Preferably, when a basic amino acid selected from the group including lysine, arginine, ornithine, diaminobutane acid and mixtures of these acids are preferably used, monoacetylated. The amino acid is an alpha-aminocarbonyl acid, if this is it on the alpha atom may be associated with hydrogen or any residue in the side chain. Main contains amino acid in the side chain, main group or more basic groups, especially amino group. The basic amino acid may be a primarily D-lysine, L-lysine or a mixture of D-lysine and L-lysine.
The composition may additionally contain salt of o-acetylsalicylic acid with naturally occurring or not naturally occurring amino acid having a minor side chain, especially with glycine. The mass ratio of lysine and glycine in the composition may range from 100:1 to 1:1, especially from 100:1 to 10:1. Preferred is a mixture of salts of the amino acids lysine and glycine. Most preferred is a salt or mixture of salts, such as contained in the composition, marketed under the trade name Aspisol®, for example, in aqueous solution.
For the purpose of the present invention can be applied also to pharmaceutical compositions containing prodrugs, which after ingestion or injection metabolized naturally in the body with the formation of active substances proposed in the invention.
According to the invention applied composition can be used for the prevention or treatment of many viral infections. The composition is most suitable for prophylaxis or treatment of infections caused by Incovinience with a negative circuit, such as influenza viruses, preferably influenza a viruses, especially viruses H5 or H7 type.
It was found also that the applied according to the invention the substance suppresses induced by the virus overexpression of cytokines ("cytokine storm"), the regulation of which depends on NF-κ. Therefore, using the proposed invention the substance can reduce overall pathogenicity of many viruses, pathogenic potential, which correlates among other things with the excess level of expression of cytokines. So used according to the invention the composition can also be used for treatment and prophylaxis of viral infections caused by a coronavirus (SARS), respiratory syncytial virus (RSV), a filovirus, such as a virus Marburg or Ebola, arenaviruses, such as Lassa virus, viruses of the Argentine, Bolivian, or Venezuelan hemorrhagic fever, Hantavirus, flaviviruses, such as Dengue or yellow fever virus, virus hemorrhagic fever Crimean-Congo virus rift valley fever, parainfluenza viruses (types 1, 2 and 3), rhinovirus, human viruses metapneumovirus (hMPV) and the virus of Epstein-Barr.
Galanov the drug proposed in the invention the pharmaceutical compositions can be prepared generally accepted in the field by the method and in the form, prigoda is Oh, in principle, for any route of administration, e.g. oral, by injection or airborne administration by inhalation. Suitable solid or liquid forms of herbal preparations are, for example, granules, powders, coated tablets, tablets, (micro) capsules, suppositories, syrups, juices, suspensions, emulsions, drops or solutions intended for injection (i.v., I.P. Pavlova., i.m., s.c.) or sprayable dispersion (aerosols), transdermal system, as well as drugs with slow release of active ingredient, for the preparation of which it is possible to apply the conventional excipients, such as carriers, disintegrating agents, binding agents, substances for the coating of substances that promote inflammation, providing the sliding or oiling agents, substances that improve the flavor, sweetening substances and substances that increase the solubility. As auxiliary substances should be mentioned magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatin, starch, cellulose and its derivatives, oils of animal and vegetable origin, such as cod liver oil, sunflower, peanut or sesame oil, polyethylene glycols and solvents, such as sterile water, and one - or polyvalent alcohols, such as glycerol, or a mixture of such solvents. The pharmacy is practical composition, used according to the invention, can be obtained by mixing at least one of the applied salt according to the invention, taken in a certain dose, with pharmaceutically acceptable and physiologically tolerated carrier and optionally with other active ingredients, additional or auxiliary substances, taken in a specific and predetermined dose, and the preparation of the formulation intended for the desired route of administration. Examples of suitable preparative forms for oral administration are described, for example, in document DE 10202019 A1 and therein references.
Preferred, however, is Galanov product intended for airborne nasal administration in the form of a liquid aqueous composition (solution) or in powder form, if possible, in the form of a suspension in the propellant, such as propellant, which can be origin at room temperature, such as chlorofluorocarbons (CFCs), hydrofluroalkane, such as 1,1,1,2-Tetrafluoroethane or 1,1,1,2,3,3,3-Heptafluoropropane, propane, butane, isobutane or other generally accepted in the field of medical aerosol preparative forms propellants. In addition to these propellants or instead you can also use air, oxygen, nitrogen, carbon dioxide or nitrous oxide. Thus the composition may contain conventional in this is blasti additional and auxiliary substances for medical aerosol preparative forms such as physiologically tolerated surfactants and/or customary in this area to facilitate the suspension means.
In addition, the aqueous composition is preferably an aqueous solution of salts or mixtures of salts with a concentration of from 0.01 mm to 3.0 M, preferably from 0.5 to 3.0 M, or from 0.01 to 100 mm, especially from 0.1 to 10 mm.
Preferably, when the size of aerosol particles formed from a solution of the salt in the form of solid substances in suspension, characterized by the value of MMAD (mass median aerodynamic diameter), less than 10 microns, preferably less than 5 microns. To measure describing the distribution of the aerodynamic particle size of the FPD values (dose of respirable particles) or FPF (fraction of respirable particles) can be used impactors, such as 5-speed multistage liquid impinger (MSLI) or 8-stage cascade impactor Andersen (ACI), which are described in Chapter 601 of the United States Pharmacopeia (USP) or the monograph Inhalanda of the European Pharmacopoeia (Ph. Eur.). Based on aerodynamic particle distribution using the "graph the logarithm of particle size is the probability of" you can count value MMAD for aerosol composition. When the preferred values MMAD is respirability particles is of arasola, so that they can penetrate into the lower region of the lung, resulting in the period of the introduction of normal duration in the entire volume of the lung is achieved by a sufficient concentration. In order to avoid removal of small particles when you exhale, it is possible to provide the lower boundary value of MAD at the level of 0.1 μm, preferably 0.5 micron.
To achieve the required values MMAD you can crush or grind used according to the invention the salt is common in this area method, for example by means of a rod, ball or vostokstrojj mill.
Introduction proposed in the invention of the aerosol can be done using any generally accepted in the field of medical equipment inhalation devices equipped with aerosol generators, such as sprinklers or spray nozzles. Examples include powder-aerosol spray guns or DPI (inhalers dry powder), jet, ultrasonic atomizers or sprayers with a vibrating membrane. You can also use aerosol generators, which are based on the electrodynamic principle or on the basis of the condensation aerosol of the liquid formulation. Examples of acceptable inhalation devices described in documents EP 1741460 AND, ER 1700614 AND, ER 1258264 and EP 1163921 A.
The salt concentration in the composition, the choice is up in accordance with the ejection velocity of the aerosol generator so so during the period of time which is less than 5 minutes, preferably 2 minutes, most preferably 1 min, could be turned into an aerosol and to enter the patient at least 10 mg, preferably at least 50 mg, most preferably at least 100 mg of salt.
In addition, for optimal deposition in the lungs, it is advisable to control and regulate the inhaled stream or inhaled volume. Because when inhaled too fast stream of aerosol particles encounter already on the back of the throat or deposited in the glottis. If too slow breath aerosol particles reach only the upper part of the respiratory tract and do not penetrate into the lower parts of the lungs. Therefore, the applicable inhalation system should provide to the patient the possibility of slow deep inhalation. For children inhalation volume should be at least 200 ml, preferably at least 500 ml For adults inhalation volume should be at least 300 ml, preferably at least 500 ml of Appropriate inhalation aerosol in this volume is carried out for a time period of at least 1, more preferably for at least 3 seconds, preferably for at least 5 spraybottle angastiniotis regulate so so he was less than 1000 ml/s, especially less than 500 ml/s, especially less than 300 ml/s, and the inhaled volume was at least 20%, especially at least 30%, preferably at least 50% and up to 95% relative to the capacity of the inhalation of the patient. The latter ensures, on the one hand, slow and on the other hand, and also a deep inhalation to patients.
For the purpose of the invention can be applied inhalation system in which the above parameters are measured by sensors and which by means of electric, acoustic and/or optical signals give information about the correct or incorrect mode of inhalation. For more information about inhalation devices that work this way, can be found in the above documents. In the case of simple inhalation systems can be provided also to pharmaceutical compositions were accompanied by written information for the patient that contains these guidelines.
Thus, the invention relates to aerosol formulations form containing salt of o-acetylsalicylic acid with naturally occurring or not naturally occurring amino acid, propellant, and optionally excipients and/or carriers. Salt may be present in the count of the operation, comprising from 0.001 to 50 wt.%, from 0.001 to 10 wt.%, first of all, from 0.1 to 10 wt.%, or from 10 to 50 wt.%, first of all, from 30 to 50 wt.%, in terms of the total weight of the preparative form. If the salt is in the form of particles, it can be characterized by the value of MAD, less than 10 μm, especially less than 5 microns.
With the invention it has been unexpectedly found that when using the above high concentrations it was possible to create formed from such solutions aerosol particles, which are characterized by the above small particle size.
In addition, the invention relates also to the application of the proposed invention in aerosol formulation for the prevention or treatment of viral infections in humans or animals in which a person or an animal, with the risk of the disease or having the disease is caused by a viral infection, introducing airborne in a physiologically effective amount of the aerosol formulation form by inhalation through the nose or mouth.
Finally, the invention relates to an inhalation device comprising a reservoir and is connected to an aerosol generator reservoir, where the reservoir contains aerosol preparative form proposed in the invention. Typically, the output of the aerosol generator attached mouthpiece. The AOC is e, can be provided by the air pump, whereby under the control of the control device control the inhalation flow and/or inhalation volume. Can be provided for controlling and/or regulating means to control and/or regulation of the inhalation flow and inhaled volume, while controlling and/or regulating means preferably set to the above values.
The above explanations about the proposed invention the pharmaceutical composition is applicable similarly to the proposed invention in aerosol formulations form, its application, and inhalation device.
The invention is explained in more detail using the following examples.
Example 1: investigation of the phenomenon of resilience
Because first of all it was required to consider the stability problems associated with the use of acetylsalicylic acid as possessing antiviral effect of an inhibitor of cellular factors, a study was conducted trends of emergence of resistant variants compared to their appearance in the application of such acting directly on the virus drugs like amantadine and oseltamivir. Cells of the pulmonary epithelium lines A infected isolatoren isolation of avian influenza virus A/FPV/Bratislava/79 (H7N7) (FPV, rinderpest virus in poultry) with MO=0,01 (multiplicity of infection), and incubated for 24 h in the presence of acetylsalicylic acid (5 mm), amantadine (5 μm) and oseltamivir (2 μm) or without them. A separate batch of lung epithelium lines A infected A/FPV/Bratislava/79 (H7N7) MO=0.001 and incubated for 24 h in the presence of lysine-glycine-atsetilsalitsilata (5 mm) and oseltamivir (2 μm) and without them. Then both parties collected the cell supernatant of each sample and it was determined viral titer analysis of belascoaran on the cell line MDCK. After that supernatant was standardized and used again for the same conditions relevant to infect the same quantities of the virus the second processed or unprocessed cell passage. This procedure was repeated to obtain a total of the fifth or the eighth passage.
On figa presents a comparison of the graphs of viral titers in cells treated with acetylsalicylic acid, or amantadine, or oseltamivir viral titers in supernatant untreated cells. It was found that in the third passage virus titers in cells treated with amantadine, again significantly increased due to the formation of resistant variants. Unexpectedly, it was found that a similar increase in juxta posing alimou value was selected for this experience experimental conditions also in the case of processing oseltamivir. It was found that acetylsalicylic acid and even in the fifth passage had all the same unmodified antiviral activity, as in the first passage, which is a strong contrast to the above results.
On figb presents a comparison of the graphs of viral titers in cells treated with lysine-glycine-atsetilsalitsilata or oseltamivir, with titles in supernatant untreated cells. It is found that when using lysine-glycine-atsetilsalitsilata was obtained a result similar to that shown in figa, in this case, even after eight passages still cannot detect the occurrence of viral resistance after treatment lysine-glycine-atsetilsalitsilata. The results fully confirm the assumption that as acetylsalicylic acid, and lysine-glycine-atsetilsalitsilata, have no tendency to cause the formation of resistant variants in cell culture.
Example 2: study of the antiviral activity of the formulation containing the lysine-glycine-atsetilsalitsilata, in relation to highly pathogenic influenza a viruses
Studied composition represented Lys-Gly-atsetilsalitsilata (hereinafter denoted as LG atsetilsalitsilata), which on the molecular composition corresponds to the product Aspisol®, manufactured by Bayer AG
Conducted a study of the antiviral activity of this formulation against influenza viruses. Cells of the pulmonary epithelium lines A infected with a virus A/FPV/Bratislava/79 (H7N7) (MO=0.01) and were incubated for 8, 24 and 36 h in the presence of acetylsalicylic acid (5 mm) or LG-atsetilsalitsilata (5 mm), or without them. Then collected the cell supernatant of each sample and determine the viral titer analysis of belascoaran on the cell line MDCK. Figure 2 presents a graph of the dependence of viral titers from time to time. The result suggests that the LG atsetilsalitsilata inhibits the multiplication of viruses highly pathogenic isolate of avian H7N7 virus with the same efficiency that and acetylsalicylic acid.
As shown in figure 3, the same takes place also in case of infection with the highly pathogenic isolates of subtype H5N1. Cells of the pulmonary epithelium lines A infected with human isolates of H5N1 virus A/Thailand/KAN-1/2004 (MOI=0.001) and incubated in the presence of acetylsalicylic acid or LG-atsetilsalitsilata in the indicated concentrations. The cell supernatant was investigated to determine viral titers using analysis belascoaran on the cell line MDCK. On figa presents data for a time of 20 h, figb presents data on the kinetics of the increase in viral titers. In both cases, the VI is but what was effective inhibition, reaching several tens of times, viral titers of H5N1 strain.
Based on the identified in vitro high antiviral potential, you can make the assumption that the preparative form containing LG-atsetilsalitsilata, you can apply for administration by inhalation as influenza active substance.
Example 3: Impact of the LG atsetilsalitsilata on highly pathogenic avian influenza viruses in the cell culture system
Cell lines MDCKII were maintained in MEM medium (MEM; firm Gibco (Invitrogen), Germany, 21430-079, 32034 lot), supplemented with 10% heat inactivated processing fetal calf serum (FCS, firm PAA Laboratories/A04305-0346), penicillin (company Grunenthal/616G03) and streptomycin (firm Sanavita/03056440111). For the implementation of the infected cells were sown in 24-well plates (8×104cells/well; firm Greiner, Germany, No. 662160, lot 05210151) and incubated over night at 37°C. Before carrying out the infected cells were washed with SFR, the corresponding virus (FPV, SNl, l) was dissolved in SR/BA (SR, supplemented with 0.6% BA (firm MP Biomedicals), 1 mm MgCh, 0.9 mm l2, penicillin (company Grunenthal/616G03) and streptomycin, and using pipettes were made on a lawn of cells with MOI, component of 0.001. After incubation for 30 min at 37°C. the virus inoculum was removed, cells were added either 1 m the environment MEM, or MEM medium containing 5 mm LG atsetilsalitsilata. After 8, 24, 32 and 48 h after infection were selected corresponding supernatant. Revealed the presence of infectious viral particles by analyzing belascoaran.
For analysis of belascoaran cell line MDCKII were sown in 96-well tablets so that a lawn of cells was achieved confluently the next day. Cells were washed with SFR and infected for 60 min at 37°C. the dilutions of supernatant, which was made in SR/BA. After incubation, the cells were layered environment, mixed with avicula (Avicel RC-581 (FMC/B624C)). This was mixed with 2.5%solution of avicel with an equal amount of 2× MEM medium. After incubation for 20 h was removed Wednesday mixed with avicula, the cells were fixed for 30 min at 4°C with 4%solution of Roti®-Histofix (firm Roth/32789170) in SFR and then washed with SFR. Necessary to carry out the dyeing stage of processing performed at room temperature. By incubation with 0.3% Triton-X-100 (firm Serva/30043) in SFR increased permeability of the cells. Virus-infected cells were stained by immunohistochemical method. For this, cells were incubated for 1 h with a monoclonal antibody (Serotec company/250107), specific against nucleoprotein influenza A. Detection of infected cells is to carried out through the implementation of another incubation (30 min) linked to horseradish peroxidase artemisinin antibody (firm DIANOV/75790) and add HRP substrate True Blue™ (KPL/070490). Dilution of the antibodies was carried out in SFR, supplemented with 10% FCS and 0.1% tween-20 (firm Serva/16211). After the implementation of the incubation with primary and secondary antibody, the cells washed three times for 5 min with SFR/0.1% tween-20. To terminate the reaction, the tablets were washed with tap water and dried. The dried tablets were subjected to scanning and evaluated using the software Corel DRAW 9.0. To determine viral titers in supernatant calculated concentrations of infected cells (foci) in each well of 96-well plate. The number of foci counted was multiplied by the appropriate dilution factor. On the basis of the obtained values was determined by the average value for each sample. Viral titer was represented as decimal logarithm (log10) of the average value.
The results are presented in figure 4. Found that as a result of processing the LG atsetilsalitsilata replication of the H7N1 virus (FPV), and H5N1 (l) in cell cultures was reduced by more than 99%.
Example 4: the Study of molecular mechanisms of action underlying the antiviral activity of the LG atsetilsalitsilata
In addition, it was studied whether comparable molecular profiles of the actions of the LG atsetilsalitsilata and pure substance, representing acetylsalicylic acid. LG atsetilsalitsilata must act in Kacha is the firmness of the inhibitor of NF-kB and therefore do not have any side effects on other induced virus signaling pathways. An important group of signaling mediators, which are also activated as a result of infection by the influenza virus, form the so-called mitogen-activated protein kinase (MARK). These include kinases JNK, R and ERK. For pure substances, representing acetylsalicylic acid, it was found that acetylsalicylic acid has no inhibitory effect on inducible virus activation of these kinases. Figure 5 shows that the same holds in the case of the LG atsetilsalitsilata: the addition of acetylsalicylic acid in a concentration of 5 mm (lane 7) or 7 mm (lane 9) does not lead to blocking induced by virus activation of JNK, R and ERK (figure 5, lane 5), which can be identified by the method of Western blotting using phosphor-specific antibodies against the active form of the kinase. The antiviral effect of acetylsalicylic acid due to the inhibition of the expression of proapoptotic factors that, in the end, leads to reduced activation of caspase in the cell. Figure 6 is demonstrated using Western blotting for LG atsetilsalitsilata, this drawing illustrates the activation of caspase revealed by splitting Casanova substrate poly-ADP-ribose-polymerase segregation (PARP). Clearly visible after 30 h, the area corresponding to cleaved PARP (lane 6), were significantly decreased to about the of ASCA, processed LG atsetilsalitsilata (lane 7).
NF-kB-dependent stage of viral replication is a dependent caspase export to the cytoplasm viral ribonucleoprotein complexes (RNP), which can then be embedded in the cell membrane of new viral particles. Acetylsalicylic acid specifically blocks this stage, with no impact on the accumulation of viral proteins at an earlier stage of the breeding cycle. In the case of the LG atsetilsalitsilata is identical mechanism of action: 7 using Western blotting demonstrated that the LG atsetilsalitsilata has no inhibitory effect on the accumulation of viral proteins Ml, NP, NSl and l. However, detected as described previously for the pure substance, representing acetylsalicylic acid, effective retention of viral RNP complexes, which is clearly seen on Fig results immunofluorescence analysis.
Based on the above we can conclude that LG-acetylsalicyl has the same antiviral potential, and acetylsalicylic acid, and has an inhibitory effect on the replication of viruses by identical molecular mechanisms.
Example 5: a Decrease in the level of expression of IP10 mRNA and interferon-gamma after processing the LG atsetilsalitsilata
From the local, that excessive production of cytokines, the so-called "cytokine storm"is an important pathogenicity factor for infections caused by influenza viruses of subtype H5N1. Since the adjustment of most of these cytokines is dependent on NF-κ, it was commanded study whether LG-ASA to inhibit expression induced by viruses, cytokines, and in consequence to exert indirect influence on the pathogenicity of these viruses. The results of the earlier inventors work demonstrated that IP10 and IFN-gamma are exposed to increasing regulation by the virus H5N1 (MV1) in the lungs of mice. The expression of this chemokine or cytokine is induced by the transcription factor NF-κB. On the basis of previously obtained data it can be shown that aspirin acts as an inhibitor of NF-κB.
The objective of this experiment was to establish whether the LG atsetilsalitsilata as an inhibitor of NF-κB in the lungs of mice after infection with H5N1. To do this, we conducted the survey, does treatment of mice LG atsetilsalitsilata before and during the infection process l influence on the rate of expression of both chemokines or cytokines. In the experiment each of the five mice of Balb/c mice were treated by i.v.-injection (100 μl) and R-injection (200 μl) of 50 mm LG atsetilsalitsilata one hour prior to the implementation of infection (inficere the General dose: 1×10 3PFU/50 μl). Subsequent processing was carried out through 17, 24 and 42 h after infection. After 48 h after infection (ri.) lungs were removed and RNA was isolated. The level of expression of IP10 and IFN-gamma in murine lungs processed LG atsetilsalitsilata mice were determined using quantitative RT-PCR and compared with the expression level in control animals. The data is presented in Fig.9.
The levels of expression of IP10 and IFN-gamma in the body untreated mice was taken as 100% in order to have the ability to make more precise comparisons. After four processing LG atsetilsalitsilata how to use intravenous, and intraperitoneal routes of administration, revealed a decrease in the level of mRNA expression of both chemokines or cytokines. When introduced intravenously was found more pronounced decrease, constituting 62% for IP10 and 68% for IFN-gamma than in the case of intraperitoneal administration (26% for IP10 and 50% for IFN-gamma).
The results indicate that induced by H5N1 virus, the expression of NF-kB-dependent genes in the lungs of treated LG atsetilsalitsilata infected mice was significantly reduced. This fact is important because excessive production of cytokines ("cytokine storm"), observed after infection with a virus subtype H5N1, the adjustment of which mainly depends on NF-kB, essentially leaet on the pathogenicity of these viruses. Thus, the LG ASA can provide not only a direct effect on virus replication, but also have an indirect positive effect by reducing the excessive production of cytokines.
Example 6: study of the tolerability
In the following experiment conducted research portability LG-atsetilsalitsilata after aerosol treatment mice. In order to optimally observe the impact of the treatment, the experiment was performed using a monitoring system of the mouse. This allowed to measure the temperature in real time. Every 5 minutes the temperature was measured and built schedule (figa-E). In addition, animals were weighed every day. At the end of the treatment period, the mice were killed and determined the mass of organs, namely the liver and spleen. Already at the first sign of toxicity in the liver is liver enlargement. In contrast, enlargement of the spleen is a sign of the presence of the inflammatory process.
For study of the tolerability a total of 12 female mice of Balb/c for 3 days before processing implanted transmitter monitoring system mouse. The success of surgery for implantation were evaluated during 3 days. After this 6 mice three times a day were processed using the Pari nebulizer, introducing each time in 2 ml of 50 mm solution of the LG acetilsalic elata. Controls served 6 mice that were treated with 2 ml SPR. The solutions were sprayed at a pressure of 1.5 bar, so that the processing took about 10 minutes Treatment was performed daily for 5 days at 9:00 am; 12:00 and 15:00 PM
Investigated the influence of the LG atsetilsalitsilata on weight change. All mice were weighed daily, starting from the date of processing, and this procedure was performed before the first treatment (9:00). Weight, measured on the first day of treatment was taken as 100%, and body weight measured in the following days, expressed in percentage in relation to it. Comparison of the results obtained for both treatment groups, presented in the form of schedule 11. From this it follows that between the group treated with the LG atsetilsalitsilata, and the group treated SFR, there was no significant difference regarding the change of body weight.
In addition, conducted a study of the influence of the LG atsetilsalitsilata at body temperature. As already mentioned, the monitoring system mouse was possible to obtain data on body temperature of the mouse in real time. Because mice have a high metabolism, then the minimum medical condition changes cause a change in body temperature. Figure 10 shows a graph of the temperature of the body, starting from day -1 (one day before treatment) (figa) before the end of the treatment period (day +4) (fige). No difference was found between those is the temperature value of the body in mice which was treated with LG atsetilsalitsilata, and body temperature in control animals.
And, finally, carried out a study of the influence of the LG atsetilsalitsilata on the weight of the liver and spleen. All animals were killed 15 min after the last treatment and carried out the autopsy. After full krovoisliania through the Vena cava conducted an investigation of the internal organs. Light is first examined through the aperture in the straightened (nepaulese) state. Liver and spleen were weighed. The results are presented on Fig. As the body weight of mice during treatment did not undergo significant changes, it was possible not to carry out the standardization of the masses. Or spleen (figa)or the liver (figb) there were no significant differences between the mass bodies of the animals were processed LG atsetilsalitsilata, and control animals. Thus, after the inhalation treatment of mice found no evidence of toxicity, which are often accompanied by swelling of the organs. In addition, there has been a systemic inflammatory reactions, which are accompanied by enlargement of the spleen.
In General, the results of this research indicate that the introduction by inhalation of 2 mg LG atsetilsalitsilata at a concentration of 50 mm for 5 days was well tolerated by the mice.
Example 7: the Experience of the patients
In clinical experience 4 patients with bronchial infections injected with a solution containing LG-ASA (50:50) at a concentration of up to 2M, which was sprayed with obtaining particle size of less than 5 microns. The total number LG-ASA ranged up to 350 mg Inhalation flow regulated to a level below 500 ml/s, in most cases below 300 ml/sec. Inhaled volume was at least 30%, in most cases at least 50% of the capacity of the breath of patients.
Three patients revealed marked improvement of symptoms the next day after the beginning of the introduction. In all other patients the improvement of symptoms occurred on day 3 after the start of injection. Thus subjectively evaluate the portability of solutions, with the highest concentration, was very good. None of the patients reported no taste irritation. Was not identified and also the urge to cough.
1. Composition for prevention or treatment of infections caused by McVie viruses with a negative chain, preferably influenza viruses, especially viruses type H5 or H7 containing salt of o-acetylsalicylic acid with an amino acid selected from the group including lysine, arginine, ornithine, diaminobutane acid and a mixture of these amino acids,
2. The composition according to claim 1, additionally containing a salt of o-acetylsalicylic acid is glycine.
3. The composition according to claim 2, in which the basic amino acid is a D-lysine, L-lysine or a mixture of D-lysine and L-lysine.
4. The composition according to any of claims 1 to 3, for the prevention or treatment of infections caused by influenza a viruses or rhinoviruses.
5. The composition according to any of claims 1 to 4, in Galanova the drug in the form of liquid water compositions primarily for airborne injection.
6. The composition according to claim 5, in which the aqueous composition is an aqueous salt solution with a concentration factor of 0.1 to 5M, primarily from 0.1 to 3M, preferably from 1 to 3M.
7. The composition according to claim 5, in which the aqueous composition is an aqueous salt solution with a concentration factor of 0.01 to 100 mm, especially from 0.1 to 10 mm.
8. Composition according to any one of claims 1 to 7, in which the composition is placed in a pharmaceutically compatible tank equipped with sprinklers or spray.
9. The composition according to claim 8, in which the tank is ready to configure inhalation flow at a level below 1000 ml/s, preferably below 500 ml/s, especially below 300 ml/s, and the inhaled volume at a level of at least 10%, especially at least 30%, preferably at least 50% and up to 95% relative to the capacity of the inhalation of the patient.
10. Application method aerosol composition comprising the salt of o-ACET salitsilovoi acid with natural or non-natural basic amino acid, propellant and optional excipient and/or carrier for the prevention or treatment of infections of humans or animals caused by McVie viruses with a negative chain, preferably influenza viruses, especially viruses type H5 or H7 viruses in which the person who is exposed to the risk of viral infection or already infected by the specified infection, or such animal, airborne is administered by inhalation through the nose or mouth physiologically effective amount of the aerosol composition.
11. The method according to claim 10, where the aerosol composition contains a salt in a quantity of 0.001 to 50 wt.%, from 0.001 to 10 wt.%, first of all, from 0.1 to 10 wt.%, or primarily from 10 to 50 wt.% in terms of the total weight of the preparative form.
12. The method according to claim 10 or claim 11, where the aerosol composition contains a salt in the form of particles or a solution where the value of MAD is less than 10 μm, especially less than 5 microns.
SUBSTANCE: invention relates to novel biologically active derivatives of 1-(1-adamantyl)ethylamine (remantadine) representing adamantyl peptides having antiviral action. The invention may find application in medicine, pharmacology and virology as new medicinal products to treat Hepatitis C.
EFFECT: obtained new low-toxic compounds have selective antiviral activity against Hepatitis C virus.
3 cl, 6 dwg, 4 ex
SUBSTANCE: method of obtaining an antiviral preparation is carried out by preparation of an inoculation mycelium of basidiomycete Enokitake Flammulina velutipes (Curtis) Singer, preparation of a liquid nutritional medium, which contains water, vegetable oil and molasses as a carbon source, as a nitrogen source - corn flour, as mineral salts - potassium dihydrophosphate and magnesium sulphate, its sterilisation, inoculation of the sterile nutritional medium with the prepared inoculation mycelium, cultivation of basidiomycete in it in an aerobic conditions; the obtained submerged culture is divided into basidiomycete biomass and a culture liquid, from which a clot is separated by addition to the latter of ethyl alcohol, which is pressed, dried and crushed with obtaining the antiviral preparation under specified conditions.
EFFECT: method makes it possible to simplify technological process, increase the output of the antiviral preparation, possessing higher activity.
2 cl, 1 tbl, 4 ex
SUBSTANCE: method of production of vaccine against foot and mouth disease comprises culturing virus antigen in suspension culture of cells BHK-21 at a temperature of 36-37°C, purification of the viral suspension from ballast impurities, inactivation, concentration of the obtained foot and mouth disease virus antigen, and connection of the antigen concentrate with an adjuvant. Purification of the virus suspension from ballast impurities is carried out by adding derived polyguanidines at a final concentration of 0.005-0.01%, or the mixture of chloroform and derivatives of polyguanidines taken in weight ratios of (40-160):1, respectively, at a final concentration of 0.4-0.8. As derivatives of polyguanidines dihydrochloride 1,12 diguanidinohexane or dihydrochloride bis (3-guanidinopropyl) piperazine, or dihydrochloride 3,6-dioxaoctane-1,8-diguanidine, or dihydrochloride 4,9-dioxadodecane-1,2-dibiguanide.
EFFECT: improvement of purification level of virus suspension from ballast impurities and increase in immunogenicity of the target product.
2 cl, 1 tbl, 16 ex
SUBSTANCE: method of production of antirabic vaccine for animals comprises preparing of inoculum from the strain of rabies virus, infection contamination with the inoculum of the culture of the continuous cells, culturing the rabies virus, collection of virus-containing suspension with its subsequent inactivation and preparation of the target product, at that the inactivation is carried out by adding the virus-containing suspension to ethanol in the final concentration of 18-20%, exposure for 20-22 hours at a temperature of 36-37°C under constant stirring, then 4-6% aluminium hydroxide is added in a ratio to the reaction mixture of 1:(4.5-5.0).
EFFECT: simplification of the method and improvement of quality of the product by increasing the shelf life of the target product.
SUBSTANCE: method of assessment of activity of therapeutic and prophylactic preparations against natural smallpox comprises administering to an animal model of control and test groups in a predetermined scheme of suspension of the antiviral preparation under study, their intranasal infection with a strain of natural smallpox virus, incubation of the virus in animal bodies and determining the concentration of virus in the lungs of animals with the subsequent calculation of estimate values of decrease in the concentration of virus in lungs. The preparation is administered to animal bodies one day prior to infecting, on the day of infecting and every day during the time of the virus incubation. The animal models are used as outbred white mice ICR of different sexes weighing 7-9 g. The strain of natural smallpox virus is used as the strain India-3a deposited at the National Collection of pathogens of viral infections and rickettsioses of the Federal budget institution of science State Research Centre of Virology and Biotechnology "Vector" under the registration number V-45.
EFFECT: adequate representation of human natural smallpox disease with use of highly virulent strain of natural smallpox virus and animal model.
1 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, namely to therapy, and concerns treating viral infections. That is ensured by administering a drug containing active ingredients presented by an activated-potentiated form of human gamma-interferon antibodies and an activated-potentiated form of CD4 receptor antibodies.
EFFECT: administering this combined drug provides effective treatment of viral diseases ensured by the synergetic antiviral effect of the active ingredients of the drug.
10 cl, 6 tbl, 5 ex
SUBSTANCE: declared group of inventions refers to the veterinary science and is applicable for treating a subclinical form caused by PCV2 infection in animals. There are declared a method of treating the subclinical form of PCV2 infection; a method of reducing a growth disorder caused by the subclinical form of PCV2 infection; a method of reducing a quantity of animals with viral load exceeding 106 genome copies per one ml of serum; a method of reducing virus isolation from a nose and//or a length of viraemia in animals infected with the subclinical form of PCV2. The declared methods involve the stage of administering a therapeutically effective amount of OFR-2 protein of PCV2 into an animal in need thereof. The subclinical form of PCV2 infection is characterised by the virus load in a body of an individual animal less than 106 genome copies of PCV2 per one ml of the serum. What is also declared is using the OFR-2 protein of PCV2 for preparing a drug for implementing the declared methods.
EFFECT: declared group of inventions is high effective for treating the subclinical form of animal's PCV2 infection.
24 cl, 5 dwg, 3 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions relates to medicine, namely to therapy, and deals with prevention and treatment of infectious viral diseases. For this purpose a complex medication, containing a mixture of several components in a form of activated-potentiated forms of antibodies to a dissolved antigen and an antigen, associated with an external membrane of immune system cells, is introduced.
EFFECT: medication ensures efficient treatment of viral diseases of different etiology due to synergic antiviral action of active medication components.
29 cl, 17 tbl, 2 dwg, 11 ex
SUBSTANCE: presented group of inventions refers to veterinary science. What is presented is an immunogenic composition for dogs containing an effective amount of parvovirus virions containing VP-2 protein having nucleic acid specified in a group consisting of SEQ ID NO:2 and SEQ ID NO:4. What is presented is a diagnostic kit for detecting parvovirus in wild and domestic animals, including animals living in zoos, reservation parks and research facilities, comprising hybridised nucleic acids specific for detecting the sequence SEQ ID NO:2 or SEQ ID NO:4 in the above animals.
EFFECT: group of inventions provides the effective aids for immunising the dogs against parvovirus, as well as diagnostic aids for detecting parvovirus in animals.
7 cl, 8 dwg, 1 tbl, 5 ex
SUBSTANCE: invention refers to a composition containing encapsulated triterpenic acid: betulinic acid, ursolic acid or derivatives thereof in the form of salts and esters, or triterpene alcohol - betulin, which may be used in medicine for treating and preventing viral infections caused by DNA and RNA-containing viruses, such as influenza viruses, oncogenic viruses, herpes virus, herpes zoster virus, as well as infections caused by gram-positive and gram-negative bacteria: Staphylococcus spp., Streptococcus spp., Enterococcus spp., Shigella spp., Escherichia spp., Salmonella spp., Proteus spp., Acinetobacter spp., Citrobacter spp., Pseudomonas spp., Serratia spp., Klebsiella spp., Antracoides spp., Cryptococcus spp., pathogenic fungi of the genus Microsporum, Trichophyton, Nocardia, Aspergillus, yeast-like fungi of the genus Candida, including multiresistant strains, as well as Actinomycetes and some pathogenic protozoa: Entamoeba histolytica, Trichomonas vaginalis. The invention presents the composition containing an active ingredient presented by 0.5 wt % of betulin or 0.5 wt % of encapsulated triterpenic acid: betulinic acid, ursolic acid or derivatives thereof in the form of salts and esters and others, and carriers presented by: β-cyclodextrins, fullerene, lecithins and polymers binding to the ingredients to form ingredient-carrier complexes, and excipients.
EFFECT: higher efficacy of using the composition.
SUBSTANCE: invention refers to medicine and presents an inhalation device for a drug dose delivery; wherein the above inhalation device comprises an aid embedding a cell containing a drug; and an aid facilitating the drug removal arranged in the embedded cell and thereby enabling removing the drug from the above cell; the aid facilitating the drug removal comprises the first fluid path extending therethrough to supply the removed drug into an outlet opening of the inhalation device; what is also enclosed is an aid used to provide the second fluid path to supply the fluid into the above cell after the above aid facilitating the drug removal pierces a sealing material of the cell.
EFFECT: invention facilitates and accelerates inhaling air and drug.
7 cl, 13 dwg
SUBSTANCE: invention relates to medical equipment, in particular to inhalators in which a medication in a reservoir with a flat lower part is transformed into an aerosol state by means of a piezoelectric vibration transformer. Essence: a signal, which has the shape of a wave, containing two sinusoidal signals at two frequencies corresponding to the main resonance frequency and additional resonance frequency is sent to the transformer to create fluctuations at two or more different frequencies, including the main resonance frequency of the transformer and at least one additional resonance frequency of the transformer.
EFFECT: increased degree of disaggregation, increased efficiency due to reduction of friction.
14 cl, 5 dwg
SUBSTANCE: rehabilitation of children with chronic microbial-inflammatory urinary diseases with the low immune status is ensured by the staged rehabilitation treatment of patients in the stage of complete and partial clinical and laboratory remission. The first stage involves a complex whereat the patient is exposed to ultraviolet short-wave beams according to the standard technique including tonsils, and endonasally according to the standard technique every second day within the 16-21-day therapeutic course. That is followed by a helper stimulation of a chest by means of Helper apparatus with using 19, 20 and 21 sternal point for 3-5 minutes for each within the 7-10-day daily therapeutic course. Therapeutic exercises and phytotherapy are prescribed next with using essences, namely sage, or mint, or aniseed, or eucalypt essences, every second day within the 7-10-day therapeutic course. Thereafter, 3-4 months later at the second stage of rehabilitation, inhalations with immunopotentiating agents, namely 0.5% lysozyme, or sodium nucleinate, or aralia infusion, or ginseng infusion, or eleuterococcus infusion, or aloe extract are prescribed in the form of 10-15 minute daily procedures. The adrenal glands are stimulated with a low-frequency alternating magnetic field generated by Polus-1 stimulator, daily for 10-20 minutes within the therapeutic course of 10-20 procedures. That is followed by the helper stimulation of a thymus by means of Helper apparatus with using 19, 20 and 21 sternal point for 3-5 minutes for each within the 7-10-day therapeutic course. The patient does therapeutic exercises. At the 3rd stage 3-4 months later, the patient is subject to an extremely high frequency electromagnetic exposure covering the middle one-third of the sternum for 5-25 minutes within the therapeutic course of 8-10 procedures, daily or every second day; or the thymus helper stimulation is applied; or a splenin or interferon phonophoresis on the submandibular lymph nodes is alternated with a complex immune preparation on wings of nose with the length of exposure 2-3 minutes within the therapeutic course of 8-10 procedures daily or every second day. The complex certainly includes a halotherapy consisting in 12-25 daily session of the length of 30 minutes, a chest massage and therapeutic exercises. The final 4th stage involves cold water treatment as provided by standard techniques, helper stimulation of the sternum and feet, therapeutic massage, therapeutic exercises, swimming, pine baths or contrast shower. The length and therapeutic course are selected individually for each child.
EFFECT: higher effectiveness of the rehabilitation treatment, namely the recovery of the main disease, reduced intercurrent infections, normalised immunogram ensured by the staged rehabilitation program aiming at the non-invasive targeted effect on the immune system.
SUBSTANCE: invention refers to an inhaler comprising an outlet and closed compartments containing a therapeutic agent. The compartment currently coupled with the outlet opens with using an opening mechanism. An indexing mechanism sequentially couples the compartments with the outlet. A lock pin is used to lock the opening mechanism in a cocked position. The lock pin cannot lock the opening mechanism, until the indexing mechanism has coupled the following compartment with the outlet. The invention also refers to a method for preparing the inhaler for an inhalation procedure and a method for delivering the therapeutic agent from the inhaler.
EFFECT: improving the inhaler performance.
13 cl, 11 dwg
SUBSTANCE: group of inventions relates to versions of inhaler, which contains outlet hole, through which distribution of medication doses can be performed. Inhaler also contains mechanism of distribution, which has charged state, in which it is ready for performing dose distribution, and activated state, in which it has already performed dose distribution. In one aspect inhaler also contains blocking device, which after realisation of last dose distribution, is activated to switch off distribution mechanism from sound generation, which was heard when distribution mechanism moved from charged state into activated state. In second aspect blocking device prevents distribution mechanism from being in its charged state when cover of outlet hole is in open position, and as a result indicator "not ready" is shown to user.
EFFECT: improvement of construction.
27 cl, 18 dwg
SUBSTANCE: group of inventions relates to medicine, and in particular to a medical dispenser comprising an outlet and closed compartments containing a drug that are used for sequential alignment with the above outlet and dispensing through the above outlet; the invention also relates to a method of digital motion of the medical dispenser. The drive motion leads to an accumulation of the mechanical energy, and then a release of the mechanical energy, and conversion it into the discrete motion of the compartments.
EFFECT: structural improvement.
14 cl, 11 dwg
SUBSTANCE: group of inventions refers to medicine, particularly to a method for dust salt generation to be used in a salt therapy, and to a dust salt generator. The dust salt generator is used for implementing the above method. Dust salt is generated when the salt particles that move in the air flow collide with each other and certain portions of the dust salt generator, and adjusting the air flow rate and thereby changing its ability to move the salt particles enables increasing the number of collisions of the salt particles, and thereby providing the more efficient dust salt generation using obstacles, such as meshes placed in a dust salt generator vessel.
EFFECT: possibility to increase the number of collisions of the salt particles, and thereby providing the more efficient dust salt generation using obstacles such as meshes that are placed in the dust salt generator vessel.
3 cl, 3 dwg
SUBSTANCE: invention refers to medicine, namely to paediatric anaesthesiology and resuscitation, and may be used for the prevention of bronchopulmonary displasia in newborns with very low or extremely low birth body weigth. For this purpose, the treatment regimen actual for the newborns on Biphasic/DuoPAP non-invasive artificial pulmonary ventilation through nasal cannula or CPAP artificial pulmonary ventilation through nasal cannula, or on invasive artificial pulmonary ventilation, is added with bolus administration of Surfactant BL from the 3rd-5th day of life in sessions of 10-15 min in a dose of 75 mg an hour. Surfactant BL is administered not later than from the 3rd-5th day of newborn's life. The preparation is administered in the amount of 75-150 ml within the therapeutic course. Omron or TravelNeb nebuliser is used.
EFFECT: invention reduces the length of newborn's being on artificial pulmonary ventilation.
SUBSTANCE: invention refers to medicine, namely to pulmonology and physiotherapy, and may be used for treating acute pneumonias in debilitated patients living in industrial cities. That is ensured by 10 daily ultrasonic inhalations of 1% placenta hydrolysate at temperature 35°C for 10 minutes on an empty stomach or 40-60 minutes after meals. The inhalations are followed by the exposure to an ultra-high frequency electric field generated by automatically resonating UHF-80-3 Undaterm apparatus of output power up to 80 Wt, high-frequency oscillation frequency 27.12±0.6 MHz. The UHF exposure covers a patient sitting of a wooden chair. Condenser plates, each of the diameter 180 mm spaced 3 cm are placed on front and back surfaces of a chest above the inflammation centre from each side. An UHF dose is low-heat, has a power of 40-60 Wt; the procedure length is 10 minute; the therapeutic course makes 10 daily procedures. After 30 minutes, the UHF exposure is followed by medicine electrophoresis through 5% placenta hydrolysate applied on one of the temporary spacers. The exposure is generated by Potok-1 apparatus having current intensity 15-20 mA; the procedure length makes 20 minutes; the therapeutic course is 10 daily procedures with the patient lying on back on a bed. Two electrodes of the same size 10x15 cm are placed in a projection of the pathological centre, i.e. the first electrode is placed on the right or on the left on the back, and the second one - on the right or on the left at the front.
EFFECT: providing faster relief of the pathological process in the pulmonary tissue, prevented development of any complication and formation of the pulmonary chronic process, including due to the manifested secretolytic effect, the high effect of bronchial apparatus drainage, normalised immune status of the respiratory mucosa.
3 tbl, 2 ex
SUBSTANCE: invention refers to medicine. A powder inhaler comprises a body with an inlet hole; an in-built storage element containing a drug powder; an in-built drug supply element comprising at least one concave area enclosing the drug capable to take up an enclosing position in relation to the storage element, wherein the concave portion encloses a pre-set amount of the drug, and an inhalation position, wherein the drug can be inhaled through the inlet hole; a mixing element for mixing the drug from the storage element; a start-up button movable between a starting position and a working position; whereas the start-up button reciprocates between the starting position and the working position, the concave area of the drug supply element moves from the enclosing position into the inhalation position, and the mixing element is actuated.
EFFECT: inhaler does not need to be shaken, and thereby can be effective in use.
7 cl, 27 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology and medicine, namely to agents possessing an inhibitory action of opportunistic bacteria, particularly on Escherichia coli O75No. 5557bacteria. The invention represents an agent inhibitinggrowth and bacterial activity of opportunistic Escherichia coli O75 No. 5557of mixed amino acids containing 1.0-2.0 mcg/ml of serine, 1.0-2.0 mcg/ml of methionine, 0.5-1.5 mcg/ml of alanine, 0.5-1.5 mcg/ml of glycine, water - the rest. The best results have been obtained when using the agent containing: 1.1 mcg/ml of serine, 1.5 mcg/ml of methionine, 0.9 mcg/ml of alanine, 0.8 mcg/ml of glycine, water - the rest. The inhibitory action of the above composition may be increased if adding anions of formic, acetic and lactic acids to the formulation in the following proportions: 1.0-2.0 mcg/ml of serine, 1.-2.0 mcg/ml of methionine, 0.5-1.5 mcg/ml of alanine, 0.5-1.5 mcg/ml of glycine, 80.0-100.0 mcg/ml of sodium lactate, 20.0-30.0 mcg/ml of sodium formate, 400.0-450.0 mcg/ml of sodium acetate, water - the rest (Version 2). The best results have been obtained when using the composition containing: 1.1 mcg/ml of serine, 1.5 mcg/ml of methionine, 0.9 mcg/ml of alanine, 0.8 mcg/ml of glycine, 89.7 mcg/ml of sodium lactate, 27.2 mcg/ml of sodium formate, 410.4 mcg/ml of sodium acetate, water - the rest. The declared composition has been coded as Composition O75.
EFFECT: invention enables preparing the compositions having the inhibitory effect of bacterial activity of Escherichia coli O75 No 5557 cells, particularly on their growth and pathogenic activity.
4 cl, 2 dwg, 4 tbl, 6 ex