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WO2022185326A1 - Compositions antivirales, anti-sars-cov-2, anti-h1n3, antibactériennes et antimicrobiennes et procédés de préparation correspondants - Google Patents

Compositions antivirales, anti-sars-cov-2, anti-h1n3, antibactériennes et antimicrobiennes et procédés de préparation correspondants Download PDF

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WO2022185326A1
WO2022185326A1 PCT/IN2021/050498 IN2021050498W WO2022185326A1 WO 2022185326 A1 WO2022185326 A1 WO 2022185326A1 IN 2021050498 W IN2021050498 W IN 2021050498W WO 2022185326 A1 WO2022185326 A1 WO 2022185326A1
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composition
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squarate
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Amitava Mazumder
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    • 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
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
    • C09D5/14—Paints containing biocides, e.g. fungicides, insecticides or pesticides

Definitions

  • TITLE ANTIVIRAL, ANTI SARS-CoV-2, ANTI H1N3, ANTIBACTERIAL AND ANTIMICROBIAL COMPOSITIONS AND METHODS OF PREPARATION THEREOF
  • the present invention relates to an antiviral composition.
  • the invention pertains to anti-SARS-CoV-2, anti H1N3, antibacterial and antimicrobial compositions which can be used for a number of purposes, including, but not limited to a coating for non-metallic surface, metallic surface for air filters, paint, packaging and methods of preparing the composition.
  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) is the causative agent of COVID-19 diseases. It belongs to Coronaviridae family and is caused by a novel coronavirus.
  • the inventors have identified the above challenges and have addressed the same by developing an anti-viral composition for preventing the spread of viral agents such as SARS CoV2.
  • the present invention overcomes the problems of the prior art to solve the problem of providing anti-viral composition for preventing the spread of viral agents such as SARS CoV2 and influenza.
  • the technical problem to be solved in this invention is the development of effective and safe anti-viral composition for preventing the spread of viral agents such as SARS CoV2 and influenza.
  • the problem has been solved by a multi dimensional approach involving developing an antiviral composition comprising squaric acid ester or croconic acid ester, amino polymer, ethanol, polypropylene glycol, glycerol and a binder solution, wherein the amino polymer is coupled with squaric acid ester or croconic acid ester.
  • the present invention represents a new prevention modality in which an antiviral composition can be used as a coating agent to stop the viral infections from spreading through contact.
  • the invention provides a method for coating a range of substrates with an anti-viral composition such that the composition acts as a barrier to block the progress of viral agents such as SARS-CoV2.
  • the coating agents can also be used in as a coating agent in applications such as filters in air conditioners and air purifiers.
  • the present invention can also act as excellent coating material on metallic and non- metallic surfaces used in packaging industries.
  • the composition is also useful in paint industries as organic non -toxic material to act as virucidal for longer duration.
  • the invention provides an antiviral composition comprising a product of a coupling reaction between amino polymer with squaric acid ester or croconic acid ester.
  • the composition may further comprises a binder, preferably organosilicon polymer such as poly dimethyl siloxane (PDMS).
  • a binder preferably organosilicon polymer such as poly dimethyl siloxane (PDMS).
  • PDMS poly dimethyl siloxane
  • the binder is polydimethyl siloxane or epoxy resins.
  • the binder is an organosilicon polymer or an epoxy resin.
  • the squaric acid ester is squaric acid monoester or squaric acid diester.
  • the squaric acid monoester ester is an alkyl squarate, an aryl squarate or a combination thereof; and squaric acid diester is a dialkyl squarate, a diaryl squarate, an alkyl aryl squarate or any combination thereof.
  • the squaric acid ester is selected from diethyl squarate and dibutyl squarate.
  • the amino polymer is selected from a group comprising deacetylated chitosan, folate-polyethylene glycol-amine, ortho-pyridyl disulfide functionalized polyethylene glycol-amine, polyethylenimine-graft-poly(ethylene glycol), polyethylenimine-graft- poly(ethylene glycol)-biotin, polyethylenimine-graft-poly(ethylene glycol)-melamide, polyethylenimine-graft-poly(ethylene glycol)-azide, polyethylenimine-graft-poly(ethylene glycol) -thiol, poly(D,L-lactide-co-glycolide)-diamine, thiol- polyethylene glycol-thiol- polyethylene glycol-amine and amine -polyethylene glycol-amine.
  • deacetylated chitosan folate-polyethylene glycol-amine
  • the chitosan is deacetylated chitosan having a degree of deacetylation of at least 80%.
  • the composition is formulated as a nano composition. The invention also provides methods for preparing the composition.
  • composition of the present invention has wide ranging application such as being used as a coating material, as a deposit and as an active ingredient in industrially used chemicals or formulations.
  • One specific use of the composition is as a coating material for air filters.
  • the invention also provides an article, a composition or formulation comprising the composition of the present invention.
  • Figure 1 depicts the FTIR for the partially quantitatively coupled product of chitosan and dibutyl squarate reaction.
  • Figure 2, 3 and 4 depicts the Mass Spectroscopic studies for the partially quantitatively coupled product of chitosan and dibutyl squarate reaction.
  • Figure 5 depicts the PXRD Analysis for the partially quantitatively coupled product of chitosan and dibutyl squarate reaction.
  • Figure 8 depicts the Scanning Electron Microscope analysis for the antiviral composition.
  • Figure 9 depicts the measurement of activity of antiviral formulations against SARS-CoV2 virus.
  • Figure 10 depicts the results of the invitro cytotoxicity.
  • amino polymer refers to a macromolecule containing one or more primary or secondary amine functional groups. In certain embodiments, amino polymers may also comprise thiol functional groups. As used herein, amino polymer refers to a macromolecule which has the capability to couple with a squaric acid ester or croconic acid ester.
  • Preferred amino polymers are selected from a group comprising deacetylated chitosan, folate -polyethylene glycol-amine, ortho- pyridyl disulfide functionalized polyethylene glycol-amine, polyethylenimine-graft-poly(ethylene glycol), polyethylenimine-graft-poly(ethylene glycol)-biotin, polyethylenimine-graft- poly(ethylene glycol)-melamide, polyethylenimine-graft-poly(ethylene glycol)-azide, polyethylenimine-graft-poly(ethylene glycol)-thiol, poly(D,L-lactide-co-glycolide)-diamine, thiol- polyethylene glycol-thiol-polyethylene glycol-amine and amine-polyethylene glycol-amine
  • binding solution refers to a solution comprising one or more components (binders) that facilitates the creation of uniform consistency, solidification and/
  • deacetylated chitosan means that the chitosan’s degree of N- deacetylation of at least 80%. In certain embodiments, deacetylated chitosan have a degree of N- deacetylation of at least 80%, at least 85%, at least 90%, at least 95% or 100%.
  • organosilicon polymers means organometallic polymers or compounds containing carbon-silicon bonds and can be suitably used in a binder solution.
  • article of manufacture refers to a product that is made and sold and that includes a container and packaging, and optionally instructions for use of the product.
  • articles of manufacture encompass packaged antiviral compositions and products containing the antiviral compositions as disclosed herein.
  • the present invention discloses anti-viral compositions which are useful for controlling a wide variety of viral as well as microbial agents, including SARS CoV2.
  • the inventors have been able to develop anti-viral compositions which represents an advancement over the existing methods for preventing viral agents such as SARS CoV2 from spreading.
  • the advances are characterized by the following features:
  • compositions can prevent the build-up of static electrical charge, and are highly effective in increasing the surface conductance.
  • the compositions are suitable for application over a wide range of surfaces.
  • compositions are non-toxic and safe. (Example 10)
  • the present invention is based on quantitative nucleophilic substitution of alkoxy groups of dialkyl squarate by free amino groups of chitosan.
  • Mono squaramide with half alkyl squarate can allow the S(-) of cysteine, N-of asparagine (side chain amino group) of Receptor Binding Domain of SARS-CoV-2 or N-terminal amino acids of protein of (S/E/M/N/RNA-bases/DNA bases) of any other RNA and DNA viruses.
  • the free amino groups of chitosan are positive due to proton abstraction from water at pH 7 thus attracting the negatively surface charged viruses namely SARS-CoV-2, Hepatitis -B, MMR etc.
  • the present investigation relates to the capture of anionic SARS-CoV-2 at neutral pH 7 by positively charged ammonium ions in an amino polymer such as chitosan which is a polysaccharide molecule having free amine groups in large number (approximately 7.6 moles of free Nitrogen in primary amine form per mole of Chitosan sample, which is 85% deacetylated).
  • an amino polymer such as chitosan which is a polysaccharide molecule having free amine groups in large number (approximately 7.6 moles of free Nitrogen in primary amine form per mole of Chitosan sample, which is 85% deacetylated).
  • Dialkyl squarates esters including croconic acid mono/di alkyl or aryl esters and 2 or 2,3 or 2,3,5 or 2, 3, 5, 6 mono/di/tri/tetra alkoxy or aryl oxy cyclohexa-2, 5-diene- 1,4 dione having active electrophilic sites to be attacked by nucleophilic sites N (for Asparagine) or S-( of Cysteine) and other nucleotide bases have been found to work nicely on SARS-CoV-2 in suitable composite liquid mixture with 99.99% efficacy and dialkyl squarates themselves show 40%-50% inhibition to cell entry for pseudo virion while experimented at cell line pH.
  • the present invention relates to the capture of anionic SARS-CoV-2 at pH 3-5.75 by positively charged ammonium ions in an amino polymer such as chitosan which is a polysaccharide molecule having free amine groups in large number (approximately 7.6 moles of free Nitrogen in primary amine form per mole of Chitosan sample, which is 85% deacetylated).
  • Chitosan (Molecular formula C56H103N9O39, molar mass 1526.5 grams/mol) contains 7.6 moles of Nitrogen as free amino groups.
  • dialkyl squarate 1%- 15% by weight esters including croconic acid mono/di alkyl or aryl esters and 2 or 2,3 or 2,3,5 or 2, 3, 5, 6 mono/di/tri/tetra alkoxy or aryl oxy cyclohexa-2, 5-diene- 1,4 dione having active electrophilic sites to be attacked by nucleophilic sites N (for Asparagine) or S-( of Cysteine) and other nucleotide bases quantitatively in one or both the sites of dialkyl squarates in reaction mixture upon heating at 55 °C with continuous stirring in ethanol and little glycerol composite solvent medium.
  • N for Asparagine
  • S-( of Cysteine) and other nucleotide bases quantitatively in one or both the sites of dialkyl squarates in reaction mixture upon heating at 55 °C with continuous stirring in ethanol and little glycerol composite solvent medium.
  • PDMS with isopropyl alcohol [20% -40% by weight], glycerol [l%-4% by weight] and PPG [15%-35% by weight] were mixed as binder of active component primary ammonium ion of chitosan and the product dialkyl squarate substituted by chitosan amino groups. It was homogeneously mixed with continuous stirring.
  • RNA is killed by the virucidal composition used here.
  • Deactivation process of SARS-CoV-2 by SN2 reaction by N of amino group of asparagine and S- of cysteine and condensation reactions are described below:
  • SARS CoV2 Squaric acid ester or ester of croconic acid All types of squarate esters like mono/dimethyl squarate, mono/diethyl squarate, mono/diisopropyl squarate, mono/dibutyl squarate or any squaric acid mono/di esters including croconic acid mono/di alkyl or aryl esters and 2 or 2,3 or 2,3,5 or 2, 3, 5, 6 mono/di/tri/tetra alkoxy or aryloxy cyclohexa-2,5-diene-l,4 dione can be used in the present invention.
  • squarate esters like mono/dimethyl squarate, mono/diethyl squarate, mono/diisopropyl squarate, mono/dibutyl squarate or any squaric acid mono/di esters including croconic acid mono/di alkyl or aryl esters and
  • the squaric acid ester is a mono ester or a diester in which two ester groups may be the same or different.
  • the squaric acid ester is squaric acid monoester (also known as squarate monoester).
  • the squaric acid monoester ester is an alkyl squarate, an aryl squarate or a combination thereof.
  • alkyl squarate include, but are not limited to, methyl squarate, propyl squarate, ethyl squarate, butyl squarate, pentyl squarate, hexyl squarate, heptyl squarate, octyl squarate, and the like.
  • the squaric acid ester is squaric acid diester (also known as squarate diester).
  • squaric acid diester is a dialkyl squarate, a diaryl squarate, an alkyl aryl squarate or any combination thereof.
  • dialkyl squarate include, but are not limited to, squaric acid dibutyl ester (SADBE), squaric acid diethyl ester (SADEE), squaric acid monobutyl ester (SAMBE), or squaric acid monoethyl ester (SAMEE).
  • SADBE squaric acid dibutyl ester
  • SADEE squaric acid diethyl ester
  • SAMBE squaric acid monobutyl ester
  • SAMEE squaric acid monoethyl ester
  • dialkyl squarate is squaric acid diethyl ester (SADEE).
  • amino polymer which provides an amino functionality and reacts with squaric acid ester or ester of croconic acid to form a corresponding coupled product may be used in the composition.
  • the amino polymer may also comprise thiol functionality.
  • amino polymer may comprise both the amino functionality and thiol functionality.
  • linear or branched polymers having polyamino or amino, SH functional groups may be used in the composition. These polymers together can act as the virucidal deposit in combination with mono/dialkyl squarates (ester) series when used in required proportion.
  • PEI-g-PEG polyethylenimine-graft-poly(ethylene glycol)
  • PEI-g-PEG-Biotin polyethylenimine-graft-poly(ethylene glycol)-biotin
  • PEI-g-PEG-Melamide polyethylenimine-graft-poly(ethylene glycol) -melamide
  • PEI-g-PEG-N3 polyethylenimine-graft-poly(ethylene glycol)-azide
  • PEI-g-PEG-SH polyethylenimine-graft-poly(ethylene glycol) -thiol
  • PLGA-Diamine 50:50 [Poly(D,L-lactide-co-glycolide)-diamine]
  • the invention provides a composition comprising squaric acid ester or croconic acid ester, amino polymer, ethanol, polypropylene glycol, glycerol and a binder solution, wherein the amino polymer is coupled with squaric acid ester or croconic acid ester.
  • the squaric acid ester is squaric acid monoester or squaric acid diester.
  • the squaric acid monoester ester is an alkyl squarate, an aryl squarate or a combination thereof; and squaric acid diester is a dialkyl squarate, a diaryl squarate, an alkyl aryl squarate or any combination thereof.
  • the squaric acid ester is selected from diethyl squarate and dibutyl squarate.
  • the amino polymer is selected from a group comprising deacetylated chitosan, folate -polyethylene glycol-amine, ortho-pyridyl disulfide functionalized polyethylene glycol-amine, polyethylenimine-graft-poly(ethylene glycol), polyethylenimine- graft-poly(ethylene glycol) -biotin, polyethylenimine-graft-poly(ethylene glycol)-melamide, polyethylenimine-graft-poly(ethylene glycol)-azide, polyethylenimine-graft-poly(ethylene glycol) -thiol, poly(D,L-lactide-co-glycolide)-diamine, thiol- polyethylene glycol-thiol- polyethylene glycol-amine and amine -polyethylene glycol-amine.
  • deacetylated chitosan folate -polyethylene glycol-amine
  • the deacetylated chitosan has a degree of N-deacetylation of at least 80%.
  • the binder solution comprises epoxyresins, organosilicon polymers or combination thereof.
  • the binder solution comprises polydimethylsiloxane, isopropyl alcohol and glycerol.
  • the concentration of squaric acid ester or croconic acid esterin the composition is in a range from 0.1% to 25% by weight.
  • the concentration of amino polymer in the composition is in a range from 1% to 50% by weight.
  • the concentration of ethanol in the composition is in a range from 5% to 25% by weight.
  • the concentration of polypropylene glycol in the composition is in a range from 15% to 35% by weight.
  • the concentration of glycerol in the composition is in a range from 1% to 4% by weight.
  • the concentration of polydimethylsiloxane in the composition is in a range from 15% to 40% by weight.
  • the concentration of isopropyl alcohol in the composition is in a range from 20% to 40% by weight.
  • the pH of the composition is in the range from 4.0 to 5.75.
  • the invention provides a composition comprising dibutyl squarate at a concentration of 1.4% w/w, chitosan at a concentration of 2.8 % w/w, ethyl alcohol at a concentration of 12.3% w/w, glycerol at a concentration of 1.4% w/w, polydimethylsiloxane at a concentration of 22.51% w/w, isopropyl alcohol at a concentration of 33.7% w/w and polypropylene glycol at a concentration of 22.4% w/w.
  • the invention provides a composition comprising diethyl squarate at a concentration of 0.3% w/w, chitosan at a concentration of 2.8 % w/w, ethyl alcohol at a concentration of 12.3% w/w, glycerol at a concentration of 1.4% w/w, polydimethylsiloxane at a concentration of 22.51% w/w, isopropyl alcohol at a concentration of 33.7% w/w and polypropylene glycol at a concentration of 23.9% w/w.
  • the invention provides an article of manufacture comprising the composition of the present invention.
  • the composition of the present invention can be used in wide ranging application such as being used as a coating material, as a deposit and as an active ingredient in industrially used chemicals or formulations.
  • One specific use of the composition is as a coating material for air filters.
  • the invention also provides an article, a composition or formulation comprising the composition of the present invention as an active ingredient.
  • composition of the present invention and deposition of nanocomposite would add one extra layer to air filters and make air virus free, especially against the most infectious virus SARS- CoV-2.
  • the composition of the present invention can be coated as a nano- deposit on glass or glass wool, paint, coat on packaging materials for various delivery system which can show excellent efficacy against SARS-CoV-2 and other viruses, can be used in AC, Air purifiers and HEPA filters, Paint, coat for packaging materials for various product delivery systems to purify air and the air turns out to be clean and pure and the painting inside room, packaging materials to be safe with this current formulation with 98% efficacy against SARS-CoV-2.
  • Any ammonium/primary/secondary/tertiary ammonium/ phosphonium ion linked with polymeric chain coupled with active substituent can deactivate any viruses namely SARS-CoV-2 or other DNA/RNA viruses/bacteria effectively.
  • the invention provides a method of preparing the antiviral composition, comprising the steps of: a. preparing a reaction mixture comprising squaric acid ester or croconic acid ester present at a concentration in a range from 0.1% to 25% by weight, amino polymer present at a concentration in a range from 1% to 50% by weight, ethanol present at a concentration in a range from 5% to 25% by weight, polypropylene glycol present at a concentration in a range from 15% to 35% by weight and glycerol present at a concentration in a range from 1% to 4% by weight; b. preparing a binder solution; and c. mixing the reaction mixture of step (a) with the binder solution in presence of propylene glycol to obtain the composition.
  • the step of preparing the reaction mixture comprises the steps of: a. adding squaric acid ester or croconic acid ester, amino polymer and ethanol to form a reaction mixture; b. adding an acid at a concentration in the range from 0.0005 M to 0.0015 M to maintain the pH of the reaction mixture at 5.25; c. adding polypropylene glycol and glycerol to the reaction mixture; and d. stirring the reaction mixture at a temperature in the range from 45-65°C to obtain the reaction mixture of step (a).
  • the invention provides a method for preparing the binder solution comprising the steps of: a. mixing polydimethylsiloxane at a concentration in a range from 15% to 40% by weight, isopropyl alcohol at a concentration in a range from 20% to 40% by weight and glycerol at a concentration in a range from 1% to 4% by weight; and b. stirring the reaction mixture to obtain the binder solution.
  • acetic acid is used to maintain the pH of the reaction mixture.
  • squaric acid ester, ester of crococnic acid, amino polymer are same as defined above.
  • the squaric acid ester is squaric acid monoester or squaric acid diester.
  • the squaric acid monoester ester is an alkyl squarate, an aryl squarate or a combination thereof; and squaric acid diester is a dialkyl squarate, a diaryl squarate, an alkyl aryl squarate or any combination thereof.
  • the squaric acid ester is selected from diethyl squarate and dibutyl squarate.
  • the amino polymer is selected from a group comprising deacetylated chitosan, folate -polyethylene glycol-amine, ortho-pyridyl disulfide functionalized polyethylene glycol-amine, polyethylenimine-graft-poly(ethylene glycol), polyethylenimine- graft-poly(ethylene glycol) -biotin, polyethylenimine-graft-poly(ethylene glycol)-melamide, polyethylenimine-graft-poly(ethylene glycol)-azide, polyethylenimine-graft-poly(ethylene glycol) -thiol, poly(D,L-lactide-co-glycolide)-diamine, thiol- polyethylene glycol-thiol- polyethylene glycol-amine and amine -polyethylene glycol-amine.
  • deacetylated chitosan folate -polyethylene glycol-amine
  • Example 1 Preparation of the anti- viral composition comprising dibutyl squarate (Formulation I)
  • a first reaction mixture (Reaction Mixture 1) was prepared using dibutyl squarate, 85% deacetylated chitosan, ethanol, acetic acid, polypropylene glycol (PPG) and glycerol. Briefly, 2 gm (0.01 moles) of dibutyl squarate, 4 gm (0.025 moles) 85% deacetylated chitosan and 17 gms ethanol was added to the reaction mixture. 0.001 M acetic acid was added to maintain pH at 5.25. Thereafter, 1 gm of polypropylene glycol and 2 gm of glycerol was added. This mixture was stirred at 55°C for 15 minutes.
  • reaction Mixture 2 as binder solution was prepared with 40 grams of polydimethylsiloxane (PDMS) and 60 grams isopropyl alcohol (IP A) and 3 grams glycerol. The reaction mixture was stirred at room temperature for 15 mins.
  • PDMS polydimethylsiloxane
  • IP A isopropyl alcohol
  • the final anti -viral composition had dibutyl squarate at a concentration of 1.4% w/w, chitosan at a concentration of 2.8 % w/w, ethyl alcohol at a concentration of 12.3% w/w, glycerol at a concentration of 1.4% w/w, polydimethylsiloxane at a concentration of 22.51% w/w, isopropyl alcohol at a concentration of 33.7% w/w, polypropylene glycol at a concentration of 22.4% w/w.
  • the anti-viral formulation had a pH of 5.25 and is in the form of a nanodeposit.
  • Example 2 Preparation of the anti- viral composition comprising diethyl squarate (Formulation II)
  • a first reaction mixture (Reaction Mixture 1) was prepared using diethyl squarate, 85% deacetylated chitosan, ethanol, acetic acid, polypropylene glycol (PPG) and glycerol. Briefly, 0.5 gm of diethyl squarate, 4 gm (0.025 moles) 85% deacetylated chitosan and 17 gm ethanol was added to the reaction mixture. 0.001 M acetic acid was added to maintain pH at 5.25. Thereafter, 3 gm of polypropylene glycol and 2 gm of glycerol was added. This mixture was stirred at 55°C for 15 minutes.
  • a binder solution was prepared with 40 grams of polydimethylsiloxane (PDMS) and 60 grams isopropyl alcohol (IPA) and 3 grams glycerol. The reaction mixture was stirred at room temperature for 15 mins.
  • PDMS polydimethylsiloxane
  • IPA isopropyl alcohol
  • the final anti-viral composition had diethyl squarate at a concentration of 0.3% w/w, chitosan at a concentration of 2.8 % w/w, ethyl alcohol at a concentration of 12.3% w/w, glycerol at a concentration of 1.4% w/w, polydimethylsiloxane at a concentration of 22.51% w/w, isopropyl alcohol at a concentration of 33.7% w/w, polypropylene glycol at a concentration of 23.9% w/w.
  • the anti-viral composition had a pH of 5.25.
  • Figure 1 depicts the FTIR for the partially quantitatively Coupled product of Chitosan and Dibutyl squarate reaction (Formulation I of Example 1). The observations were made during FTIR studies with 85% Chitosan and FTIR studies with squaric acid dibutyl ester were compared.
  • PXRD Analysis was performed on the coupled product as depicted in Figure 5, Figure 6 and Figure 7.
  • the PXRD result shows the peaks at 2 Theta of 10 degree, 20 degree (sharp peak), 30 degree, 35 degree and 40 degree. This is due to the particular plane in chitosan.
  • N primary amine of chitosan substituted shows shift of sharp peak at 23 degree with other peaks at 18degree and 35degree. This shift indicate that the distortion of the diffracting plane due to bond formation of chitosan and dibutyl squarate confirmed by FTIR.
  • Example 7 Measurement of activity against MS2 Bacteriophage on plastics and other non- porous surfaces and coating materials
  • MS2 Bacteriophage is an RNA virus of the family Leviviridae. Escherichia coli ATCC 15597 are the hosts for bacteriophages. Due to its environmental resistance, MS2 bacteriophages are used as a surrogate virus (particularly in place of Picornaviruses such as Poliovirus and human Norovirus) in water quality and antimicrobial studies. Pre-sterilized samples were loaded with diluted viral suspension to 10 6 PFU/ ml.
  • Virus suspension at an inoculation volume of 0.4 ml was added to 50 mm x 50 mm of Test substrate. It was covered with 40 mm x 40 mm low density polyethylene (LDPE). Following exposure time, virus was eluted and neutralized by serial tenfold dilution and assayed to determined surviving viruses in comparison with Control without test product in sq. cms. Assay with antiviral formulation comprising dibutyl sauarate
  • Uo Log of PFU recovered from Untreated specimen immediately after inoculation, in PFU/ cm 2
  • U t Log of PFU recovered from Untreated specimen after 2/24 hrs after inoculation, in PFU/ cm 2
  • a t Log of PFU recovered from Treated specimen after 2/24 hrs after inoculation, in PFU/ cm 2 .
  • Virus assay was quantitative as Plaque forming unit (PFU) visible as area of clearance. The results are depicted in the following table:
  • Uo Log of PFU recovered from Untreated specimen immediately after inoculation, in PFU/ cm 2
  • U t Log of PFU recovered from Untreated specimen after 20 mins after inoculation, in PFU/ cm 2
  • a t Log of PFU recovered from Treated specimen atler 20 mins after inoculation, in PFU/ cm 2
  • the formulation has a very high efficacy of 97.52% reduction of bacteriophage MS2 within 20 minutes.
  • Assay with antiviral formulation comprising dibutyl sauarate dried at 75°C
  • Uo Log of PFU recovered from Untreated specimen immediately after inoculation, in PFU/ cm 2
  • U t Log of PFU recovered from Untreated specimen after 2/24 hrs after inoculation, in PFU/ cm 2
  • a t Log of PFU recovered from Treated specimen after 2/24 hrs after inoculation, in PFU/ cm 2 .
  • Uo Log of PFU recovered from Untreated specimen immediately after inoculation, in PFU/ cm 2
  • U t Log of PFU recovered from Untreated specimen after 2/24 hrs after inoculation, in PFU/ cm 2
  • a t Log of PFU recovered from Treated specimen after 2/24 hrs after inoculation, in PFU/ cm 2 .
  • Example 8 Measurement of activity against Influzena virus on plastics and other non- porous surfaces and coating materials
  • MDCK cell ATCC CCL-34 were used as the hosts for the virus.
  • TCID50 infectivity titer method was used. Pre-sterilized samples were loaded with diluted viral suspension to 10 6 PFU/ ml. Virus suspension at an inoculation volume of 0.4 ml was added to 50 mm x 50 mm of Test substrate. It was covered with 40 mm x 40 mm low density polyethylene (LDPE). Following exposure time, virus was eluted and neutralized by serial tenfold dilution and assayed to determined surviving viruses in comparison with Control without test product in sq. cms. Virus assay was quantitative as Plaque forming unit (PFU) visible as area of clearance. The results are depicted in the following table:
  • Uo Average of common logarithm from three control/ untreated specimen immediately after inoculation
  • U t Average of common logarithm from three control/ untreated specimen after 2 hours
  • a t Average of common logarithm from three treated specimen after 2 hours
  • the formulation has a very high anti-viral activity of 99.95% against Influenza A virus (H3N2) within 2 hours.
  • Example 9 Measurement of activity of antiviral formulations against SARS-CoV2 virus A study was conducted for measuring antiviral activity of the Formulation I against S ARS
  • CoV2 virus The study was conducted at Centre for Cellular and Molecular Biology, India.
  • a viral RNA extraction assay and qRT-PCR assay was performed on the composition and glass slide coated with the composition.
  • Viral RNA Extraction assay was performed using a MagMAXTM Viral/Pathogen Extraction Kit (manufactured by Applied Biosystems, Thermo Fisher). Further, the qRT-PCR assay was performed using a Meril Covid-19 One- Step RT-PCR Kit (manufactured by Meril Diagnostics Pvt. Ltd.)
  • Example 10 In vitro Cytotoxicity Assay
  • Test for cytotoxicity are designed to determine the biological response of mammalian cells to the test material/ Extract of test material. At the end of the exposure time, the evaluation of the presence and the extent of Cytotoxic effect is assessed. Cytotoxicity tests signifies biological compatibility of the test material and its potential to cause cell damage.
  • test standards used were:
  • L929 cells (Mouse connective tissue) from Passage no. 90 (PN 90) were seeded in 96 well plates at a concentration of 10,000 cells per 100 m ⁇ of MEM culture medium with 10% FBS per well were maintained in culture for 24 hours to form a semi confluent layer and were exposed to the test material over a range of concentration from 1% to 10%.
  • the positive control used was 0.001% SDS (Sodium Dodecyl sulphate) solution and negative control was Complete MEM medium with 10% FBS.
  • the cell lines were incubated at 37°C with with 5% Carbon dioxide atmosphere.
  • Formazan formation is determined for each treatment concentration and compared to that determined in growth control. For each treatment the percentage inhibition of growth is calculated by Viability of cells as per formula -
  • Evaluation criteria was set as: • The lower the viability percentage value, the higher the cytotoxic potential
  • the surface resistivity of the antiviral composition was measured. The results are provided in the below table:
  • Electro-static dissipative range 10 6 -10 9 Ohm/Square Antistatic range: 10 10 -10 11 Ohm/Square Insulator range: 10 12 -10 13 Ohm/Square
  • the results indicate that the compositions can be used as anti-static agents which prevents the build-up of static electrical charge. They are effective in increasing the surface conductance or reduces surface resistivity and are suitable for use over wide range of applications.

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Abstract

La présente invention concerne une composition antivirale, anti-SARS-CoV-2, anti-H1N3, antibactérienne et antimicrobienne et des procédés de préparation correspondants. Les compositions comprennent un ester d'acide squarique ou un ester d'acide croconique, un polymère aminé, de l'éthanol, du polypropylène glycol, du glycérol et une solution de liant, le polymère aminé étant couplé à un ester d'acide squarique ou à un ester d'acide croconique. La composition de la présente invention a une large application de télémétrie, comprenant, sans s'y limiter, un revêtement pour surface non métallique, une surface métallique pour filtres à air, une peinture, un emballage et des procédés de préparation de la composition.
PCT/IN2021/050498 2021-03-03 2021-05-21 Compositions antivirales, anti-sars-cov-2, anti-h1n3, antibactériennes et antimicrobiennes et procédés de préparation correspondants Ceased WO2022185326A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024214114A1 (fr) * 2023-04-10 2024-10-17 Amitava Mazumder Compositions thérapeutiques et méthodes de traitement du cancer

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005074947A2 (fr) * 2003-12-10 2005-08-18 Sd Pharmaceuticals, Inc. Compositions pharmaceutiques antivirales
WO2008105934A2 (fr) * 2006-09-22 2008-09-04 Oregon Biomedical Engineering Institute, Inc. Utilisation de chitosane pour inactiver des agents toxiques et pathogènes
WO2012159215A1 (fr) * 2011-05-24 2012-11-29 Polyvalor S.E.C. Compositions et procédés pour l'administration efficace et sûre d'arnsi à l'aide de nanocomplexes spécifiques à base de chitosane

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005074947A2 (fr) * 2003-12-10 2005-08-18 Sd Pharmaceuticals, Inc. Compositions pharmaceutiques antivirales
WO2008105934A2 (fr) * 2006-09-22 2008-09-04 Oregon Biomedical Engineering Institute, Inc. Utilisation de chitosane pour inactiver des agents toxiques et pathogènes
WO2012159215A1 (fr) * 2011-05-24 2012-11-29 Polyvalor S.E.C. Compositions et procédés pour l'administration efficace et sûre d'arnsi à l'aide de nanocomplexes spécifiques à base de chitosane

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024214114A1 (fr) * 2023-04-10 2024-10-17 Amitava Mazumder Compositions thérapeutiques et méthodes de traitement du cancer

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