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WO2025071439A1 - Composition intranasale pour la prévention et/ou le traitement d'infections d'étiologie virale et bactérienne - Google Patents

Composition intranasale pour la prévention et/ou le traitement d'infections d'étiologie virale et bactérienne Download PDF

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Publication number
WO2025071439A1
WO2025071439A1 PCT/RU2024/050226 RU2024050226W WO2025071439A1 WO 2025071439 A1 WO2025071439 A1 WO 2025071439A1 RU 2024050226 W RU2024050226 W RU 2024050226W WO 2025071439 A1 WO2025071439 A1 WO 2025071439A1
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Prior art keywords
composition
poviargol
composition according
molecular weight
sodium hypochlorite
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English (en)
Russian (ru)
Inventor
Геннадий Евгеньевич Афиногенов
Анна Геннадьевна Афиногенова
Светлана Константиновна МАТЕЛО
Тамаз Омарович МАНАШЕРОВ
Игорь Валерьевич АМБРОСОВ
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Obschestvo S Ogranichennoi Otvetstvennostyu "wds"
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Obschestvo S Ogranichennoi Otvetstvennostyu "wds"
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Priority claimed from RU2023124744A external-priority patent/RU2825642C9/ru
Application filed by Obschestvo S Ogranichennoi Otvetstvennostyu "wds" filed Critical Obschestvo S Ogranichennoi Otvetstvennostyu "wds"
Publication of WO2025071439A1 publication Critical patent/WO2025071439A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the invention relates to the field of medicine, namely pharmacology, and can be used for the prevention and/or treatment of viral and bacterial infections of the nasopharynx, nasal cavity, including coronavirus infection, influenza, and other acute respiratory viral infections.
  • the nasal cavity is an antimicrobial filter, which is widely represented by air microflora, including fungal spores, bacilli, micrococci, nonpathogenic Neisseria, epidermal staphylococcus, beta-hemolytic streptococcus. Facultative inhabitants of the nose include pneumococci, Klebsiella pneumoniae, Staphylococcus aureus, influenza bacteria, Candida. These species can cause autoinfection: rhinitis, bronchitis, nasopharyngitis, pneumonia, and also be a source of infection for other people. In children, the nasal microflora is even more numerous and diverse.
  • the prototype of the claimed solution is the invention according to patent RU 2616523 C1 (17.04.2017, IPC A61K9/06, A61K31/22, A61K36/61, A61K36/53, A61P31/04, A61P31/16), which is an intranasal ointment for the treatment and prevention of respiratory infections.
  • the invention is characterized by a prolonged effect, which is provided by the synergism of the individual components of the drug.
  • the results of using the drug were shown in patients with influenza and acute respiratory viral infections.
  • the authors of this invention do not indicate the required frequency and duration of use of the intranasal ointment, which will achieve the stated treatment and prevention.
  • the objective of the present invention is to solve the problem of the lack of an effective broad-spectrum composition for the prevention and/or complex treatment of infectious and inflammatory diseases of the nasal cavity when administered intranasally.
  • the technical result of the invention is the creation of a more effective, compared to the prototype, broad-spectrum composition for the prevention and/or complex treatment of infectious and inflammatory diseases of the nasal cavity with intranasal use, possessing prolonged broad antimicrobial activity, in particular, with respect to human coronavirus, influenza virus, other RNA- and DNA-containing viruses and bacteria, possessing the ability to prevent the formation and destroy already formed microbial biofilms.
  • compositions for application to the nasal cavity characterized by the fact that it contains high-molecular hyaluronic acid, high-molecular polyvinylpyrrolidone (PVP), gelofusin, sodium hypochlorite, poviargol, an antibacterial polypeptide, which is gramicidin C or lysozyme, in the following ratio of components, wt. %:
  • Antibacterial polypeptide (gramicidin C - 0.03-0.15, or lysozyme - 0.1-18.0);
  • the subject of the invention is also the use of the claimed composition for the prevention and/or treatment (especially during periods of exacerbation of seasonal infectious diseases, epidemics and pandemics) of infectious and inflammatory diseases of the nasal cavity caused by coronaviruses, influenza virus, other RNA- and DNA-containing viruses and bacteria, accompanied by the formation of microbial biofilms, characterized in that the composition is applied to the mucous membrane of the nasal cavity for prophylactic or therapeutic purposes once a day.
  • high-molecular hyaluronic acid in the context of the present invention characterizes non-sulfated glycosaminoglycan, which is part of connective, epithelial and nervous tissues.
  • High-molecular hyaluronic acid is one of the main components of the extracellular matrix, is contained in many biological fluids (saliva, synovial fluid, etc.), plays a significant role in the proliferation and migration of cells, is produced by some bacteria (Nair. Streptococcus.
  • the body of a person weighing 70 kg contains on average about 15 grams of hyaluronic acid, a third of which is converted (broken down or synthesized) every day.
  • Hyaluronic acid is the main structure-forming glycosaminoglycan, since it has the ability to concentrate other glycosaminoglycans around itself and form proteoglycan aggregates that have greater hydrophilicity and elasticity compared to free proteoglycans.
  • hyaluronic acid By binding collagen fibers, other proteins and components of the intercellular substance and even cells into a single system, hyaluronic acid creates a “buffer volume” that determines the strength and elasticity of mechanical tissues, helping them to overcome temporary impact (N.N. Sigaeva, S.V. Kolesov, P.V. Nazarov, R.R. Vildanova. Chemical modification of hyaluronic acid and its use in medicine // Bulletin of the Bashkir University. 2012. Vol. 17. No. 3. Pp. 1220-1241).
  • High-molecular medical polyvinylpyrrolidone in the context of the present invention characterizes binding agent.
  • High-molecular PVP is available as a powder of the "pharmaceutically pure” grade, a free-flowing white or yellowish-white powder with particles of various sizes, a specific odor.
  • the average molecular weight of PVP is 1,000,000-1,500,000 Da [VolkerBuhler. Kollidon®. Polyvinylpyrrolidone for the pharmaceutical industry / Translation from English, edited by Doctor of Philosophy K.V. Alekseev. BASF: 2001. - 310 p.].
  • An aqueous solution of PVP is a sterile, viscous, transparent, slightly colored liquid with a specific, weak odor.
  • biodegradable carriers based on high-molecular PVP, which allow for the long-term presence of antibacterial substances in the wound, their local use both for the purpose of prevention in metalloosetting synthesis and for the treatment of surgical infections.
  • the molecular weight of PVP is of great importance in this case.
  • Modification of biologically active substances with high-molecular polymers is carried out for the purpose of targeted change of their properties: reduction of toxicity, improvement of solubility, pharmacokinetics and bioavailability due to complexation [Afinogenov G.E., Panarin E.F. Antimicrobial polymers, 1993. Publishing house “Gipppokrat", St. Moscow. - 260 p.].
  • the main function of soluble high-molecular PVP is to prolong the action of medicinal preparations with improved bioavailability.
  • poviargol in the context of the present invention characterizes highly dispersed metallic silver stabilized by low-molecular medical polyvinylpyrrolidone; it is a light powder from greenish-gray to greenish-brown color. In medical practice, poviargol is used as an aqueous solution for external use, which is prepared immediately before use.
  • Poviargol is a broad-spectrum antimicrobial agent, active against aerobic and anaerobic microflora, including antibiotic-resistant ones. In concentrations up to 100 ⁇ g/ml, it inhibits the growth of most bacteria (staphylococci, streptococci, Pseudomonas aeruginosa and Escherichia coli, Proteus, Shigella, Salmonella, etc.).
  • the drug in concentrations of 1-3% has an anti-inflammatory effect and stimulates reparative processes in the wound at the stage of epithelialization; it is low-toxic, does not has an irritating effect on the skin and mucous membranes, does not cause allergic reactions and dermatitis.
  • Poviargol is used as an antimicrobial agent for the prevention and treatment of purulent-septic complications of wounds, ulcers, burns and bedsores, including those that do not heal for a long time when treated with antibiotics; in infectious diseases of the upper respiratory tract, ear, throat, nose, eyes and oral cavity; in diseases of the genitourinary system and musculoskeletal system [http://sktb-technolog.ru/poviargolum2; "Poviargol: a new bactericidal agent for the treatment of infected wounds. (Experience of clinical use in traumatology, purulent surgery, burn therapy, gynecology, urology and ophthalmology). Reference manual for doctors / Ed. Corresponding Member of the Russian Academy of Sciences Panarin E.F., Doctor of Medical Sciences, Professor Blagitko E.M. Novosibirsk: Publishing house. 1998. - 66 p.
  • sodium hypochlorite in the context of the present invention characterizes an effective antiseptic.
  • the range of its application areas includes disinfection of laboratory equipment, water disinfection, local treatment of wounds, etc.
  • Sodium hypochlorite exhibits its biological activity through reactions with nucleic and amino acids. In reactions with nucleic acids, in particular DNA, it chlorinates bases, preventing the formation of hydrogen bonds, which initiates denaturation of the molecule and, as a consequence, loss of biological activity.
  • lysozyme in the context of the present invention characterizes an enzyme of the innate immune system of a large number of different organisms, from prokaryotes to higher eukaryotes. Being 1,4-L-O-N-acetyl muramidase, it is, among other things, capable of exhibiting chitinase activity, hydrolyzing glycosidic bonds of bacterial peptideglycan, activating autolysins and exhibiting antiviral activity, including against HIV. At the same time, the protein has a fairly low toxicity, and even when doses sufficient to achieve a bactericidal effect are exceeded, no significant effect on the patient's body was detected.
  • gramicidin C in the context of the present invention characterizes a molecule of organic origin and serves as a natural defense mechanism for the Bacillus brevis bacterium, which begins producing the substance in response to a threat to its vital activity.
  • the antibiotic has a polypeptide structure, has a bacteriostatic (preventing the reproduction of bacteria) and bactericidal (destroying bacteria) effect.
  • the mechanism of action of gramicidin C is associated with an increase in the permeability of the cytoplasmic membrane of the microbial cell, which disrupts its stability and causes cell death.
  • Gramicidin C is cyclic sequence of amino acids, and such a structure allows preventing the development of resistance of microorganisms to this antibiotic, while at the moment, the development of addiction to the drug in various bacterial pathogens has not been described in the available literature, which is important for the effectiveness of treatment.
  • gelofusine in the context of the present invention characterizes a 4% solution of succinylated gelatin (also known as modified liquid gelatin) for intravenous administration with an average molecular weight of 23,200 daltons. It has a colloid osmotic pressure of 34 mm Hg. The isoelectric point is reached at pH 4.5. Negative charges arising in the molecule as a result of succinylation lead to an increase in the size of the molecule and, thus, more voluminous protein chains are formed than non-succinylated ones, while maintaining the molecular weight. As a result, Gelofusine has a sufficient volemic effect for 3-4 hours. Gelofusine is used as a colloidal plasma substituting agent.
  • FIG. 1 Kinetics of interaction of viral RNA with sodium hypochlorite.
  • FIG. 5 Control of human lung adenocarcinoma cell culture (ATCC® CRL-5800), h600.
  • FIG. 6 Control of the cytotoxic effect of coronavirus OC43 on human lung adenocarcinoma cell culture (ATCC® CRL-5800), x900.
  • FIG. 7 Morphological picture of the state of the culture of human lung adenocarcinoma cells (ATCC® CRL-5800) in the presence of coronavirus OC43 and a polymer composition of three polymers, xbOO.
  • a) Mixture 1 x 10' 4 M;
  • C NaCl 3.5 x 10' 4 M;
  • C NaCl 8.0 x 10' 4 M.
  • FIG. 10 Relationship between the bactericidal action of an intranasal composition and the time of its exposure to different microorganisms.
  • FIG. 11 Bactericidal action of the intranasal composition and the antimicrobial ingredients included in its composition.
  • FIG. 12 Visualization of the intranasal composition on the nasal mucosa after 8 hours of application.
  • FIG. 13 - No visualization of the intranasal composition based on the prototype on the nasal mucosa after 8 hours of application.
  • FIG. 14 (B) Experimental sample of 0.5 MF Staphylococcus aureus.
  • FIG. 14 (B) Prototype 0.5 MF Staphylococcus aureus.
  • FIG. 15 (B) Experimental sample of 0.5 MF Pseudomonas aeruginosa.
  • FIG. 15 (B) Prototype 0.5 MF Pseudomonas aeruginosa.
  • FIG. 16 (B) Experimental sample of 0.5 MF Acinetobacter baumannii.
  • FIG. 16 (B) Prototype 0.5 MF Acinetobacter baumannii.
  • FIG. 17 (B) Experimental sample of 0.5 MF Klebsiella pneumoniae.
  • FIG. 17 (B) Prototype 0.5 MF Klebsiella pneumoniae.
  • the claimed composition for the prevention and/or treatment, alone or as part of a complex therapy of infectious and inflammatory diseases of the nasal cavity with intranasal use, which has prolonged antimicrobial activity against human coronavirus, influenza virus, other RNA- and DNA-containing viruses and bacteria, the ability to prevent the formation and destroy already formed microbial biofilms, includes components in the following ratio, May. %:
  • the amount of high molecular weight hyaluronic acid can also be 0.5-2 wt.%, 0.5-1 wt.%, or 1-2 wt.%.
  • the amount of high molecular weight PVP can also be 4.5-5.5 wt%.
  • the amount of poviargol can also be 0.8-1 wt%.
  • the amount of lysozyme can also be 1-16.0 wt%.
  • the claimed composition can be used for prevention on its own, as well as as part of complex therapy for infectious and inflammatory diseases of the nasal cavity caused by coronaviruses, influenza viruses, other RNA- and DNA-containing viruses and bacteria, by applying it (application) to the mucous membrane of the nasal cavity.
  • composition all powdered components (hyaluronic acid, polyvinylpyrrolidone, poviargol, gramicidin C (or lysozyme)) are dissolved sequentially in a sodium hypochlorite solution, observing the above-mentioned quantitative ratios, and a gelofusin solution is added to 100.0 wt.%, mixed until a homogeneous mass is obtained.
  • hyaluronic acid, polyvinylpyrrolidone, poviargol, gramicidin C (or lysozyme) are dissolved sequentially in a sodium hypochlorite solution, observing the above-mentioned quantitative ratios, and a gelofusin solution is added to 100.0 wt.%, mixed until a homogeneous mass is obtained.
  • the preparation of the claimed composition based on gelofusin, high-molecular hyaluronic acid and polyvinylpyrrolidone provides a prolonged effect due to the formation of a protective barrier film on the mucous surface of the nasal cavity, which contributes to the long-term antimicrobial effect of poviargol and sodium hypochlorite, moisturizing the nasal passages, which, in turn, reduces the risk of developing irritation, dryness of the nasal mucosa, pain reaction, bleeding.
  • the ratio of the components of the claimed composition is the result of extensive experimental studies and is optimally suited to achieve the above results.
  • a significant advantage of the claimed composition is the presence of a prolonged antimicrobial effect against a wide range of RNA- and DNA-containing viruses and bacteria, microbial biofilms, and the absence of side effects.
  • a special feature of the claimed composition is the formation of a thin polymer barrier film on the mucous surface of the nasal cavity with a single applications, which ensures high sorption of viral and bacterial particles for one hour.
  • poviargol during the first 50 seconds accelerates the denaturing effect of sodium hypochlorite on viral RNA or viral and bacterial DNA.
  • RNA-containing viruses The antiviral activity against RNA-containing viruses of the proposed intranasal composition of the following composition, wt. %, was studied:
  • the proposed intranasal composition reliably reduced the titers of the influenza virus and coronavirus OC43 in cell culture.
  • the antiviral efficacy against RNA-containing viruses was at least 99.9% within 3 minutes of exposure.
  • RNA-containing viruses The antiviral activity against RNA-containing viruses of the proposed intranasal composition of the following composition, wt. %, was studied:
  • the proposed intranasal composition reliably reduced the titers of the influenza virus and coronavirus OC43 in cell culture.
  • the effectiveness of the antiviral action against RNA-containing viruses was at least 99% during a 3-minute exposure.
  • RNA-containing virus coronavirus
  • Gramicidin polypeptide antibiotic
  • Gramicidin polypeptide antibiotic
  • Lysozyme (antibacterial polypeptide) - 16.0
  • Lysozyme antibacterial polypeptide
  • Gramicidin polypeptide antibiotic
  • Lysozyme (antibacterial polypeptide) - 16.0.
  • poviargol silver nanoparticles
  • the different course of time dependences in different regions of the spectrum indicates the interaction of sodium hypochlorite with various RNA components present in the solution.
  • it is the wavelength region of 260 nm that can reflect the interaction of sodium hypochlorite with the nitrogenous bases of the polynucleotide.
  • the nature of the time dependences of the relative change in absorption and its rate in the region of X 260 nm, which characterizes the state of nitrogenous bases in polynucleotides, is similar for viral and synthetic RNA. It indicates that the process of interaction of polynucleotides with hypochlorite has at least 2 stages. The first is rapid, expressed in an increase in the intensity of absorption, which is usually associated with denaturation or destruction of the secondary structure of the polynucleotide. At this stage, chlorination of nitrogenous bases occurs. At the second stage, gradual destruction of nitrogenous bases occurs, caused by the products formed at the first stage of interaction.
  • virus-containing liquid initial titer of coronavirus OC43 6.5 1g; influenza virus 7.5 lg
  • influenza virus 7.5 lg influenza virus 7.5 lg
  • the samples were centrifuged for 20 minutes at 3000 rpm and the infectious activity of the virus was determined in the supernatant.
  • cell culture medium was used instead of the polymer combination.
  • Figures 5-7 show the morphological picture of the state of the cell culture in the presence of the test coronavirus OS43 and a polymer composition of three polymers - high-molecular PVP and hyaluronic acid on gelofusin.
  • poviargol silver nanoparticles
  • hypochlorite complexes with plasmid DNA were prepared.
  • the complexes were prepared by direct mixing. An aqueous solution of sodium chloride NaCl with an ionic strength of 0.015 M was used as a solvent.
  • the absorption of the solution increases in the entire absorption region of DNA.
  • the total spectrum is close to the sum of the spectra of DNA and sodium hypochlorite of the concentrations used.
  • the substances used in the work have a characteristic absorption spectrum in the wavelength range from 220 to 500 nm.
  • the above spectrophotometer operates in a dual-beam mode. In all measurements, the cuvette space for the background solution remained empty, i.e. the measurements were performed relative to atmospheric air, the absorption of which in the range under consideration did not exceed D ⁇ r ⁇ 0.005. After each measurement, the cuvette with the solution was washed and used to measure the solvent used in the previous measurement. The solvent spectrum was subtracted at the data processing stage using the Origin software package.
  • the solutions were prepared using laboratory electronic scales (accuracy 0.0002 g) and dispensers, stirring was performed using a Vortex.
  • FIG. 9 Analysis of the time derivative of the change in absorption at 260 nm (FIG. 9) shows that the first step of the DNA destruction reaction occurs much faster. This is consistent with the fact that poviargol (silver nanoparticles) induces denaturation of microbial DNA in the presence of sodium hypochlorite, making nitrogenous bases more accessible for the chlorination reaction.
  • the proposed intranasal composition destroys RNA- and DNA-containing viruses and bacteria.
  • Bacterial isolates were obtained from loci of patients from different departments of a multidisciplinary healthcare facility, and the proposed antimicrobial composition was tested using the “checkerboard” method.
  • the antiseptics - sodium hypochlorite, poviargol, included in the intranasal composition were used in subbactericidal doses, which are hundreds and thousands of times lower than the permitted doses of individual drugs for clinical local use.
  • lysozyme has a very weak antibacterial effect on gram-negative microorganisms [Renata Cegielska-Radziejewska Grzegorz Lesnierowski • Tomasz Szablewski • Jacek Kijowski. Physico-chemical properties and antibacterial activity of modiWedeggwhite — lysozyme // Eur Food Res Technol (2010) 231 :959–964; DOI 10.1007/s00217-010-1347-y; Goncharova A.I., Okulich B.K., Zemko V.Yu., Senkovich S.A.
  • Klebsiella pneumoniae 5299639 isolated from the wound discharge of a patient with a maxillofacial profile, was used. This isolate was characterized by resistance to 8 groups of antimicrobial drugs, including carbapenems.
  • the proposed intranasal composition was tested using the “checkerboard” method with an exposure time of 1.5 hours.
  • the composition was preliminarily supplemented with crushed activated carbon to improve visualization. All subjects were given the proposed intranasal composition once in both nasal passages, then the subjects squeezed the wings of the nose with their fingers to distribute the composition evenly over the mucosal surface. Under anterior rhinoscopy conditions using a hardware method (STORZ Karl Storz Endoscope tele pack XLEDTP100 device), the distribution of the intranasal composition over the nasal mucosa was assessed 8 hours after application. In all volunteers, a continuous, uniform distribution of the intranasal composition over the mucous membrane of the anterior sections of the nasal cavity was observed at all times, which indicated the presence of the proposed intranasal composition during the 8 hours of observation (FIG. 12).
  • example 1 presented above showed a decrease in the titer of coronavirus OC43 during co-incubation with the intranasal composition for 3 minutes, which was 3 1g (the titer of the virus in the control was 6.5 1g).
  • the decrease in the titer of the virus OC43 during incubation with the intranasal composition with lysozyme was 1.5 lg (when the titer of the virus in the control was 4.7 1g).
  • the proposed hydrogel has higher efficiency compared to the prototype.
  • the prototype preparation did not have a bactericidal effect on test cultures of microorganisms. Microbial growth was noted on Petri dishes (FIG. 14 (B), FIG. 15 (B), FIG. 16 (B), FIG. 17 (B)). Moreover, the intranasal composition according to example 7 leads to a decrease in the microbial population by 4-5 1g in relation to all gram-positive and gram-negative microorganisms.
  • the claimed composition is more effective than the prototype drug in terms of both virucidal and bactericidal activity.

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Abstract

L'invention se rapporte au domaine de la médecine, notamment de la pharmacologie, et peut être utilisée pour la prévention et/ou le traitement d'infections d'étiologie virale et bactérienne du rhinopharynx, de la cavité nasale, y compris des infections par le coronavirus, la grippe et autres infections respiratoires virales aiguës. Cette composition intranasale pour la prévention et/ou le traitement de maladies infectieuses-inflammatoires de la cavité nasale comprend de l'acide hyaluronique de poids moléculaire élevé, de la polyvinylpyrrolidone de poids moléculaire élevé (PVP de poids moléculaire élevé), du poviargol, un polypeptide antibactérien, une solution d'hypochlorite de sodium, de la gelofusine, les composants étant pris dans des proportions déterminées.
PCT/RU2024/050226 2023-09-26 2024-09-25 Composition intranasale pour la prévention et/ou le traitement d'infections d'étiologie virale et bactérienne Pending WO2025071439A1 (fr)

Applications Claiming Priority (2)

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RU2023124744A RU2825642C9 (ru) 2023-09-26 Интраназальная композиция для профилактики и/или лечения инфекций вирусной и бактериальной этиологии
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RU2481101C2 (ru) * 2010-12-15 2013-05-10 Владимир Николаевич Иванов Фармацевтическая композиция, содержащая ферменты: лизоцим, пероксидазу, повиаргол и липосомы, для местного применения
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RU2481101C2 (ru) * 2010-12-15 2013-05-10 Владимир Николаевич Иванов Фармацевтическая композиция, содержащая ферменты: лизоцим, пероксидазу, повиаргол и липосомы, для местного применения
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