[go: up one dir, main page]

WO2016039412A1 - Agent antibactérien et procédé de fabrication d'un agent antibactérien - Google Patents

Agent antibactérien et procédé de fabrication d'un agent antibactérien Download PDF

Info

Publication number
WO2016039412A1
WO2016039412A1 PCT/JP2015/075696 JP2015075696W WO2016039412A1 WO 2016039412 A1 WO2016039412 A1 WO 2016039412A1 JP 2015075696 W JP2015075696 W JP 2015075696W WO 2016039412 A1 WO2016039412 A1 WO 2016039412A1
Authority
WO
WIPO (PCT)
Prior art keywords
antibacterial agent
antibacterial
cyanoacrylate
organic acid
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2015/075696
Other languages
English (en)
Japanese (ja)
Inventor
千頭邦夫
山本繁男
飯田大介
岡田純
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chikami Miltec Inc
Original Assignee
Chikami Miltec Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chikami Miltec Inc filed Critical Chikami Miltec Inc
Priority to JP2016547498A priority Critical patent/JPWO2016039412A1/ja
Publication of WO2016039412A1 publication Critical patent/WO2016039412A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A01N25/10—Macromolecular compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/06—Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/34—Nitriles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N61/00—Biocides, pest repellants or attractants, or plant growth regulators containing substances of unknown or undetermined composition, e.g. substances characterised only by the mode of action

Definitions

  • the present invention relates to an antibacterial agent containing cyanoacrylate polymer particles as an active ingredient and a method for producing the same.
  • antibacterial agents having an antibacterial effect against bacteria such as Gram-positive bacteria.
  • Patent Document 1 describes an antibacterial agent containing cyanoacrylate polymer particles conjugated with an antibiotic as an active ingredient as an antibacterial agent for vancomycin-resistant gram-positive bacteria.
  • the cyanoacrylate polymer particles are obtained by anionic polymerization of a cyanoacrylate monomer that is used, for example, as an adhesive for wound closure in the surgical field. Cyanoacrylate-based polymer particles are porous, and a desired substance can be conjugated inside.
  • VRE vancomycin-resistant enterococci
  • Patent Document 2 discloses particles that adhere to the cell wall of Gram-positive bacteria and do not adhere to mammalian cell membranes and have a particle size of 5 ⁇ m or less, and that are substantially free of antibacterial active ingredients against Gram-positive bacteria.
  • An antibacterial agent for Gram-positive bacteria contained as an active ingredient is described.
  • Patent Document 2 uses particles composed of a cyanoacrylate polymer, and when a single particle that is not conjugated with an antibacterial drug is first applied to bacteria, a lysis phenomenon was found following specific adhesion between the particles and the bacterial cell wall. Is.
  • Patent Document 2 Since the antibacterial agent of Patent Document 2 is an antibacterial agent that transcends the bacterial drug resistance mechanism, it can be applied to gram-positive bacteria exhibiting multidrug resistance typified by methicillin-resistant Staphylococcus aureus (MRSA) and VRE, It is also said that the emergence of new multidrug-resistant bacteria, which is a major problem in the use of antibiotics, can be avoided.
  • MRSA methicillin-resistant Staphylococcus aureus
  • VRE methicillin-resistant Staphylococcus aureus
  • Patent Document 3 describes an antibacterial agent for Gram-positive bacteria that contains Kumazasa leaf extract as an active ingredient. It is said that Kumazasa leaf extract does not show antibacterial activity against Escherichia coli or Pseudomonas aeruginosa, which are Gram-negative bacteria, but shows antibacterial activity against Gram-positive bacteria.
  • Patent Document 4 describes that cyanoacrylate polymer particles conjugated with amino acids are synthesized by anionic polymerization of cyanoacrylate monomers in the presence of amino acids to synthesize cyanoacrylate polymer particles having an average particle diameter of less than 1000 nm.
  • the amino acid-conjugated particles of Patent Document 4 are said to be useful for the treatment and prevention of cancer because they can damage cancer cells by inducing apoptosis-like cell death to cancer cells.
  • Legionella which is a Gram-negative bacterium, is a non-acid-fast bacterium, and is said to grow by infesting other predatory protozoa such as amoeba using metabolites of other bacteria and algae. Legionella bacteria in the biofilm inhabited by these organisms are considered to be protected from the outside world. Since the biofilm is formed in a pipe or a filter, the biofilm serves as a protective film, and it has been difficult to kill Legionella even by sterilization with, for example, a chlorine agent.
  • an object of the present invention is to provide an antibacterial agent having an antibacterial action against more bacterial species and a method for producing the same.
  • the first characteristic constitution of the antibacterial agent according to the present invention for achieving the above object is that it contains, as an active ingredient, cyanoacrylate polymer particles containing an organic acid in at least one form of conjugation or mixing.
  • Patent Documents 1 and 2 also have antibacterial properties against gram-negative bacteria (such as Escherichia coli, Legionella, Pseudomonas aeruginosa, Salmonella, and Klebsiella pneumoniae) for which antibacterial effects have not been observed.
  • the antibacterial agent of the present invention can be lysed by contacting cyanoacrylate polymer particles obtained by conjugating or mixing an organic acid with a peptidoglycan layer of Gram-positive bacteria.
  • the antibacterial agent of the present invention is a cyanoacrylate polymer particle in which an organic acid as an antibacterial active ingredient acts on an outer membrane (capsule) composed of lipopolysaccharide of Gram-negative bacteria cells, and an organic acid is conjugated or mixed.
  • an organic acid as an antibacterial active ingredient acts on an outer membrane (capsule) composed of lipopolysaccharide of Gram-negative bacteria cells, and an organic acid is conjugated or mixed.
  • the antibacterial agent of the present invention can control the antibacterial activity by changing the concentration of cyanoacrylate polymer particles conjugated or mixed with an organic acid.
  • concentration of cyanoacrylate polymer particles conjugated or mixed with organic acid can be kept constant, and the antibacterial activity can be controlled by changing only the concentration of organic acid. It can be demonstrated.
  • the antibacterial agent of the present invention is recognized as having an excellent cleaning effect on pipes and the like on which scale is deposited. Furthermore, as shown in Example 6 described later, a biofilm or the like formed in a pipe or a filter can be decomposed using the antibacterial agent of the present invention. As for these cleaning / decomposing effects, the cleaning / decomposing performance can be controlled by changing only the concentration of the organic acid.
  • the antibacterial agent of the present invention has not only an excellent antibacterial effect but also an excellent cleaning effect on piping and the like. Therefore, the antibacterial performance of the antibacterial agent of the present invention, in addition to sterilizing Legionella, which is a Gram-negative bacterium that requires anti-infection measures especially in cooling devices and water circulation facilities, Biofilm to be washed can be cleaned and decomposed. Further, the antibacterial agent of the present invention is effective not only for cooling devices and water circulation facilities but also for toilets and kitchens.
  • a sheet prepared by applying a dispersion containing the antibacterial agent of the present invention to a nonwoven fabric or the like can be used as an antibacterial sheet that exhibits antibacterial performance against various bacteria.
  • the antibacterial property of the antibacterial sheet is excellent in safety and lasts gently for a long time.
  • the second characteristic constitution of the antibacterial agent according to the present invention is that it is produced by anionic polymerization of the cyanoacrylate monomer in the presence of a cyanoacrylate monomer, a saccharide and an organic acid.
  • the antibacterial agent of the present invention can be produced by synthesizing cyanoacrylate polymer particles in which an organic acid is efficiently conjugated or mixed by anion polymerization of a cyanoacrylate monomer.
  • the third characteristic configuration of the antibacterial agent according to the present invention is that the average particle size of the cyanoacrylate polymer particles is less than 1000 nm.
  • the cyanoacrylate polymer particles can be handled as so-called nanoparticles.
  • the antibacterial agent of the present invention is used in the form of a dispersion, if the cyanoacrylate polymer particles are nanoparticles, the particles do not aggregate and settle, and the dispersion stability is excellent.
  • the fourth characteristic constitution of the antibacterial agent according to the present invention is that it is produced by anionic polymerization of the cyanoacrylate monomer in the presence of a surfactant.
  • the average particle diameter of the cyanoacrylate polymer particles can be reduced to about 10 to 50 nm. If the average particle size of the cyanoacrylate polymer particles can be reduced in this way, the specific surface area of the cyanoacrylate polymer particles can be greatly increased, and the number of antibacterial nanoparticles can be increased at the same concentration. Therefore, the antibacterial power can be greatly improved. If the antibacterial activity is desired to be maintained, the concentration of the antibacterial agent can be lowered, so that the cost can be reduced.
  • miniaturization can improve the transparency of the antibacterial nanoparticle dispersion, and the spray nozzle used when spraying the antibacterial nanoparticle dispersion is less likely to be clogged.
  • the improvement of the transparency of the dispersion is effective when the antibacterial agent of the present invention is actually applied to the liquid. For example, when an antibacterial agent is applied in the liquid in the culture or rearing of fish, the transparency is improved, so that the stress on the fish can be reduced, and the state of the liquid in the tank of the ornamental fish is easy to see. Become.
  • the fifth characteristic configuration of the antibacterial agent according to the present invention is that the antibacterial agent is produced by anionic polymerization of the cyanoacrylate monomer in the presence of the cyanoacrylate monomer, the surfactant and the organic acid.
  • the cyanoacrylate monomer is anionically polymerized, and cyanoacrylate polymer particles in which an organic acid is efficiently conjugated or mixed are synthesized.
  • Antibacterial agents can be manufactured.
  • the average particle diameter of the cyanoacrylate polymer particles can be reduced to about 10 to 50 nm.
  • the sixth characteristic configuration of the antibacterial agent according to the present invention is that the cyanoacrylate monomer is butyl cyanoacrylate.
  • the seventh characteristic configuration of the antibacterial agent according to the present invention is that the organic acid is selected from the group consisting of glycolic acid, fumaric acid, citric acid, acetic acid and lactic acid.
  • an organic acid having antibacterial properties can be used.
  • the eighth characteristic configuration of the antibacterial agent according to the present invention is that the saccharide is a polysaccharide having a hydroxyl group.
  • the first characteristic means of the method for producing an antibacterial agent according to the present invention is that the antibacterial agent is produced by anionic polymerization of the cyanoacrylate monomer in the presence of a cyanoacrylate monomer, a saccharide and an organic acid.
  • the antibacterial agent of the present invention can be produced by synthesizing cyanoacrylate polymer particles obtained by anionic polymerization of a cyanoacrylate monomer and efficiently conjugating or mixing an organic acid.
  • the second characteristic means of the method for producing an antibacterial agent according to the present invention is that the step is performed in the presence of a surfactant.
  • the average particle diameter of the cyanoacrylate polymer particles can be reduced to about 10 to 50 nm.
  • the third characteristic means of the method for producing an antibacterial agent according to the present invention is that the antibacterial agent is produced by anionic polymerization of the cyanoacrylate monomer in the presence of a cyanoacrylate monomer, a surfactant and an organic acid. .
  • the cyanoacrylate monomer is anionically polymerized, and cyanoacrylate polymer particles in which an organic acid is efficiently conjugated or mixed are synthesized to produce the present invention.
  • Antibacterial agents can be manufactured.
  • the average particle diameter of the cyanoacrylate polymer particles can be reduced to about 10 to 50 nm.
  • the antibacterial agent of the present invention contains, as an active ingredient, cyanoacrylate polymer particles containing an organic acid in at least any form of conjugation or mixing.
  • the antibacterial agent in the present invention contains cyanoacrylate polymer particles containing an organic acid as an active ingredient in a form of conjugation or mixing.
  • This embodiment demonstrates the case where it is set as the aspect of the cyanoacrylate polymer particle (organic acid conjugate particle
  • the antibacterial agent may be any form such as a particle dispersion, a particulate form, a granular form, etc., as long as it contains cyanoacrylate polymer particles containing an organic acid as an active ingredient in at least any form of conjugation or mixing. It may be.
  • the dispersion may take a form such as a suspension or a colloidal liquid, but is not limited thereto.
  • the cyanoacrylate polymer portion of the conjugated particle is obtained by anionic polymerization of a cyanoacrylate monomer.
  • the cyanoacrylate monomer used is preferably an alkyl cyanoacrylate monomer (the alkyl group preferably has 1 to 8 carbon atoms), and is particularly used as an adhesive for sutures in the surgical field. It is preferable to use butyl cyanoacrylate represented by the formula.
  • butyl cyanoacrylate such as isobutyl cyanoacrylate, n-butyl-2-cyanoacrylate, sec-butyl cyanoacrylate, tert-butyl cyanoacrylate, etc. can be used, and methyl cyanoacrylate, ethyl cyanoacrylate ( Other alkyl cyanoacrylates such as adhesive for false eyelashes) and propyl cyanoacrylate may be selected.
  • isobutyl cyanoacrylate, n-butyl-2-cyanoacrylate, and ethyl cyanoacrylate are excellent in safety.
  • saccharides may be used for stabilizing the polymerization. That is, the “cyanoacrylate polymer particles” of the present invention include those containing a polymerization stabilizer such as a saccharide.
  • the saccharide is not particularly limited, and may be any of a monosaccharide having a hydroxyl group, a disaccharide having a hydroxyl group, and a polysaccharide having a hydroxyl group, and is particularly preferably a polysaccharide.
  • monosaccharides include glucose, mannose, ribose and fructose, and glucose is preferred.
  • the disaccharide include maltose, trehalose, lactose and sucrose.
  • polysaccharide dextran, mannan, or the like used for the polymerization of conventionally known cyanoacrylate polymer particles can be used.
  • These sugars may be either cyclic or chain-like, and when they are cyclic, they may be any one of pyranose type, furanose type and the like.
  • isomers of sugar there are various isomers of sugar, and any of them may be used.
  • monosaccharides exist in a pyranose type or furanose type form, and disaccharides are those in which they are ⁇ -bonded or ⁇ -bonded, and sugars in such a normal form can be used as they are.
  • any one having a function of stabilizing the polymerization of anionic polymerization such as polyethylene glycol and a surfactant, can be used.
  • the saccharides, polyethylene glycols and surfactants mentioned above can be used alone or in combination of two or more.
  • dextran is preferable, and dextran having a degree of polymerization having an average molecular weight of about 10,000 to 500,000 is preferable, but is not limited thereto.
  • nonionic surfactants and ionic surfactants can be used as the surfactant, but are not limited thereto.
  • the ionic surfactant is preferably an anionic surfactant, but is not limited thereto.
  • nonionic surfactant for example, Tween 20 (polyoxyethylene sorbitan monolaurate) can be used, and as an anionic surfactant, for example, alkylbenzenesulfonic acid or a salt thereof, sodium lauryl sulfate, sodium laureth sulfate, etc. can be used. It is not limited. Nonionic surfactants and anionic surfactants may be used simultaneously. At this time, the anionic surfactant is preferably used in a smaller amount (about 1/10) than the nonionic surfactant.
  • the organic acid-conjugated particles are less likely to aggregate over time. That is, because the organic acid-conjugated particles are produced by anionic polymerization, the organic acid-conjugated particles themselves have an anionic property, and the organic acid-conjugated particles repel each other by using an anionic surfactant. It is presumed that this prevents aggregation. Further, the anionic surfactant may be used (input) at any stage at the start of polymerization and after the end of polymerization.
  • the cyanoacrylate polymer particles are porous, and a desired substance can be conjugated inside.
  • the desired substance may be conjugated to the inside of the cyanoacrylate polymer particles by immersing the cyanoacrylate polymer particles in an aqueous solution of the desired substance or adding the desired substance.
  • the desired substance may be conjugated to the produced particles by performing the above-described anionic polymerization in the presence of the desired substance.
  • an organic acid is conjugated to the cyanoacrylate polymer particles. Conjugation refers to a state in which a foreign substance is held in, for example, a hydrophilic molecule.
  • glycolic acid As the organic acid, glycolic acid, fumaric acid, citric acid, acetic acid, lactic acid and the like having antibacterial properties can be used.
  • these organic acids at least one or more can be selected and used.
  • glycolic acid has the smallest molecular weight among organic acids and is excellent in permeability. These organic acids can be used as long as they have antibacterial properties.
  • Water can be used as a solvent for the polymerization reaction.
  • Purified water, ion-exchanged water, distilled water, pure water, tap water, ground water, etc. may be appropriately selected as the water depending on the product application having different required purity.
  • the antibacterial agent of the present invention can be produced by performing anionic polymerization of a cyanoacrylate monomer in the presence of a cyanoacrylate monomer, a saccharide and an organic acid.
  • the polymerization reaction is performed, for example, by dissolving a polymerization stabilizer such as an organic acid and a saccharide to be conjugated to water as a solvent, adding a cyanoacrylate monomer under stirring, and continuing stirring. be able to.
  • reaction temperature is not specifically limited, It is good to carry out at room temperature.
  • the reaction time is not particularly limited because the reaction rate varies depending on the pH of the reaction solution, the type of solvent and the concentration of the polymerization stabilizer, and may be appropriately selected depending on these factors, but is usually about 1 to 6 hours. It is.
  • the concentration of the cyanoacrylate monomer in the polymerization reaction solution at the start of the reaction is not particularly limited, but is usually about 0.01 to 5%, preferably about 0.1 to 3%.
  • the concentration of the organic acid in the polymerization reaction solution at the start of the reaction is not particularly limited, but is usually about 0.01 wt% to 10 wt%, preferably about 0.05 wt% to 5 wt%, more preferably 0.05 wt% to 3 wt%. It may be about%.
  • the concentration of the saccharide in the polymerization reaction solution at the start of the reaction is not particularly limited, but is usually about 0.01 to 5%, preferably about 0.1 to 3%.
  • the antibacterial agent of the present invention can be produced by anionic polymerization of the cyanoacrylate monomer by the polymerization reaction described above and synthesizing cyanoacrylate polymer particles (organic acid-conjugated particles) efficiently conjugated with an organic acid. If two or more organic acids are allowed to coexist during anionic polymerization, an antibacterial agent having organic acid-conjugated particles conjugated with two or more organic acids can be produced.
  • the synthesized organic acid-conjugated particles can be used as an antibacterial agent in the state of a particle dispersion dispersed in a solvent.
  • the obtained particle dispersion hardly changes over time in the particle size distribution during storage, and the particles do not aggregate or settle even when stored at rest, and is excellent in dispersion stability.
  • the concentration of the organic acid-conjugated particles may be about 0.01 wt% to 5 wt%, preferably about 0.05 wt% to 3 wt%, more preferably about 0.1 wt% to 2 wt%.
  • the synthesized organic acid-conjugated particles can be recovered by conventional filtration such as centrifugal ultrafiltration and used as an antibacterial agent in a particulate or granular state. Furthermore, the organic acid conjugate particles recovered by filtration can be used as an antibacterial agent in a state of a particle dispersion in which the particles are dispersed in a solvent such as water.
  • the particle size of the synthesized organic acid-conjugated particles is not particularly limited, but is usually nano-order size (less than 1000 nm), preferably 1 nm to 1000 nm, more preferably about 10 nm to 600 nm.
  • the particle size can be adjusted by adjusting the concentration of cyanoacrylate monomer in the reaction solution and the reaction time.
  • the particle size can also be adjusted by changing the concentration and type of the polymerization stabilizer.
  • the average particle diameter of the organic acid-conjugated particles can be reduced to about 10 to 50 nm.
  • the pH of the reaction solution affects the polymerization rate.
  • the pH of the reaction solution is high, the hydroxyl ion concentration is high, so that the polymerization is fast, and when the pH is low, the polymerization is slow. Therefore, the pH is preferably about 1 to 4.
  • organic acid-conjugated particles can be stably synthesized at an appropriate speed due to the acidity of an organic acid without using hydrochloric acid as in the prior art.
  • the salt (NaCl) that is an impurity is not generated by the neutralization.
  • the particle dispersion has high transparency because of the small average particle diameter of the organic acid-conjugated particles. Such a particle dispersion having high transparency is less uncomfortable during use.
  • the antibacterial agent of the present invention can be lysed by contacting organic acid-conjugated particles with a peptidoglycan layer of Gram-positive bacteria.
  • the antibacterial agent of the present invention has antibacterial properties against gram-negative bacteria that have not been recognized as having an antibacterial effect in the past (for example, Patent Documents 1 and 2). This is because the organic acid, which is an antibacterial active ingredient, acts on the outer membrane (capsular membrane) composed of lipopolysaccharides of Gram-negative bacterial cells, and the organic acid-conjugated particles pass through the outer membrane by breaking it. As a result of contacting the organic acid-conjugated particles with a peptidoglycan layer, it is considered that lysis was possible.
  • Examples of the target bacterial species to which the antibacterial agent of the present invention has an antibacterial effect include, but are not limited to, gram-negative bacteria and gram-positive bacteria that are bacteria that synthesize cell walls.
  • Gram-negative bacteria include Escherichia coli, Legionella, Pseudomonas aeruginosa, Salmonella, Neisseria pneumoniae
  • Gram-positive bacteria include Staphylococcus aureus (methicillin-resistant Staphylococcus aureus (MRSA)), enterococci ( Vancomycin-resistant enterococci (VRE)), streptococci (pneumococcus streptococci, oral streptococci, pyogenes streptococci, peptostreptococcus bacteria, etc.), diphtheria, propionibacterium acnes, acid-fast bacilli Tuberculosis mycobacteria and the like), but is not limited thereto.
  • MRSA methicillin-resistant Sta
  • biofilms and the like formed in pipes and filters can be decomposed using the antibacterial agent of the present invention.
  • inorganic salts such as calcium carbonate, calcium sulfate, silica, and the like contained in the water deposit on the inner wall as a scale.
  • the scale is very hard and hardly soluble in water. For example, even if a metal tool is used, it is difficult to scrape off manually.
  • the antibacterial agent of the present invention is used, the scale can be easily removed by washing.
  • glycolic acid when glycolic acid is used as the organic acid in the antibacterial agent of the present invention, glycolic acid has the smallest molecular weight among organic acids and is excellent in permeability, and thus has an excellent cleaning and removing effect on the scale.
  • the antibacterial agent of the present invention has not only an excellent antibacterial effect but also an excellent cleaning effect on piping and the like. Therefore, the antibacterial performance of the antibacterial agent of the present invention, in addition to sterilizing Legionella, which is a Gram-negative bacterium that requires anti-infection measures especially in cooling devices and water circulation facilities, Biofilm to be washed can be cleaned and decomposed.
  • a sheet prepared by applying a dispersion containing the antibacterial agent of the present invention to which a glycolic acid is applied is applied to a nonwoven fabric or the like, it is useful for preventing and treating acne in addition to antibacterial effects against various bacteria.
  • the sheet can be used as a patch for preventing bedsores such as bedridden patients.
  • the antibacterial agent of the present invention was produced as follows.
  • glycolic acid organic acid: manufactured by Wako Pure Chemical Industries, Ltd.
  • dextran produced by Wako Pure Chemical Industries, Ltd.
  • the reaction solution was filtered through a 5 ⁇ m sized membrane filter (manufactured by Sartorius: Mini Zalto), and purified water was added to prepare a 0.1 wt% antibacterial nanoparticle dispersion (glycolic acid concentration 0.05 wt%).
  • the average particle size of the organic acid-conjugated particles obtained at this time was 170 nm as measured by a usual method using a Zetasizer (Nano-ZS90 manufactured by Malvern).
  • FIG. 1 shows a photograph of the organic acid-conjugated particles observed with an electron microscope ( ⁇ 50000).
  • Example 2 Using the 0.1 wt% antibacterial nanoparticle dispersion prepared in Example 1 (glycolic acid concentration 0.05 wt%: Invention Example 1), Escherichia coli NBRC 3972, Gram-negative bacteria, Staphylococcus aureus (Staphylococcus aureus subsp. Aureus NBRC 12732, Gram-positive bacteria), antibacterial effect on methicillin-resistant Staphylococcus aureus (MRSA: Staphylococcus aureus IID 1677, Gram-positive bacteria) was examined.
  • MRSA Staphylococcus aureus IID 1677, Gram-positive bacteria
  • the antibacterial nanoparticle dispersion liquid of Inventive Example 1 has about 1/50 of the number of bacteria reduced after 24 hours against E. coli and almost detected after 24 hours against S. aureus and MRSA. It was recognized that the number of bacteria had decreased to an infeasible level. Therefore, it was recognized that the antibacterial agent of the present invention has antibacterial properties against gram-negative bacteria and gram-positive bacteria.
  • Example 1 In place of the 0.1 wt% antibacterial nanoparticle dispersion (glycolic acid: Invention Example 1) prepared in Example 1, cyanoacrylate polymer particles conjugated with glycine, an amino acid (Comparative Example 1: For example, Patent Document 4) ) Dispersion (0.1 wt%) was tested for antibacterial effects against E. coli, Staphylococcus aureus and MRSA. The number of viable bacteria was measured according to the above method. The results are shown in Table 2.
  • the dispersion of Comparative Example 1 showed no significant reduction in the number of bacteria compared to S. aureus and MRSA even after 24 hours against E. coli (a reduction of about a quarter). It was observed that the number of bacteria decreased from 1/1000 to an almost undetectable level after 24 hours for Staphylococcus aureus and MRSA. Therefore, it was recognized that the dispersion liquid of Comparative Example 1 has antibacterial properties only for Gram-positive bacteria.
  • Comparative Example 2 Instead of the 0.1 wt% antibacterial nanoparticle dispersion (glycolic acid: Invention Example 1) prepared in Example 1, a dispersion (0.1 wt%) of cyanoacrylate polymer particles (Comparative Example 2) was used. The antibacterial effects against E. coli, Staphylococcus aureus and MRSA were examined. The number of viable bacteria was measured according to the above method. The results are shown in Table 3.
  • the dispersion of Comparative Example 2 showed no significant reduction in the number of bacteria compared to S. aureus and MRSA even after 24 hours against E. coli (a reduction of about 1/5). It was observed that the number of bacteria decreased from 1/100 to almost undetectable levels after 24 hours for Staphylococcus aureus and MRSA. Therefore, it was recognized that the dispersion liquid of Comparative Example 2 has antibacterial properties only for Gram-positive bacteria.
  • Example 3 Instead of the 0.1 wt% antibacterial nanoparticle dispersion prepared in Example 1 (glycolic acid concentration 0.05 wt%: Invention Example 1), a solution of glycolic acid (Comparative Example 3) (0.05 wt%) was used. Used to examine the antibacterial effect against E. coli. The number of viable bacteria was measured according to the above method. The results are shown in Table 4.
  • Comparative Example 3 showed no significant decrease in the number of bacteria compared to S. aureus and MRSA even after 24 hours against E. coli (a decrease of about one third). .
  • the antibacterial effect (about 1/50) of the organic acid-conjugated particles (glycolic acid) of Invention Example 1 against E. coli is antibacterial against the Escherichia coli of the cyanoacrylate polymer particles of Comparative Example 2. It was recognized that there was a remarkable antibacterial effect as compared with the effect (a reduction of about 1/5) and the antibacterial effect of glycolic acid of Comparative Example 3 on E. coli (a reduction of about 1/3). That is, by using cyanoacrylate polymer particles (Comparative Example 2) and glycolic acid (Comparative Example 3) alone, organic acid-conjugated particles of the Invention Example 1 (cyanoacrylate polymer particles conjugated with glycolic acid). It was recognized that it has a remarkable antibacterial effect synergistically.
  • Example 3 0.1 wt% antibacterial nanoparticles using fumaric acid and citric acid as organic acids in the same manner as the 0.1 wt% antibacterial nanoparticle dispersion (glycolic acid: Invention Example 1) prepared in Example 1 Dispersions (Invention Examples 2 and 3) were prepared.
  • the control physiological saline and the sample (Invention Examples 1 to 3) were diluted with physiological saline so that they would be 100 times, 1000 times, and 10,000 times after the bacterial inoculation. In culture. Samples including the control (Invention Examples 1 to 3) were statically cultured at 28 ° C. for 24 hours, and the number of colonies was counted. The results are shown in Table 5.
  • the antibacterial agent of the present invention also has antibacterial properties against gram-negative bacteria by containing organic acid-conjugated particles using glycolic acid, fumaric acid and citric acid as organic acids. Similar results were obtained when lactic acid was used as the organic acid (data not shown). Further, in this example, the case where the concentration of the antibacterial nanoparticle dispersion was set to 0.1 wt% was shown, but similar results were obtained when the concentration was 0.01 wt% or 10 wt% (data not shown). ).
  • Example 4 Using the 0.1 wt% antibacterial nanoparticle dispersion prepared in Example 1 (glycolic acid: Invention Example 1), the number of surviving Legionella pneumophila GIFU 9134 (Gram negative bacteria) in this dispersion was measured. Legionella was added to control purified water and the dispersion of Invention Example 1 and allowed to stand at room temperature, and the number of viable bacteria after 6, 24 and 48 hours at the start was counted. The results are shown in Table 6.
  • Example 1 of the present invention As a result, the control purified water showed no change in the number of bacteria even after 48 hours, but in Example 1 of the present invention, it was recognized that it decreased to about 1 / 70,000 after 48 hours. . Thereby, it was recognized that the antibacterial agent of this invention has remarkable antibacterial property also to Legionella bacteria.
  • the behavior of the antibacterial nanoparticle dispersion liquid for Legionella bacteria and Escherichia coli, which are Gram-negative bacteria is considered to be the same, even when the test for Escherichia coli of Example 2 (up to 24 hours) was performed for up to 48 hours, It is expected to decrease to about 1 / tens of thousands as in the embodiment.
  • Example 5 By a method according to the antibacterial nanoparticle dispersion (glycolic acid) prepared in Example 1, a dispersion having a glycolic acid concentration of 3.0 wt% (Invention Example 4) was prepared by adding glycolic acid after the polymerization reaction. . Using this dispersion, a cleaning test of the scale deposited on the metal plate was performed. Water was used as a control.
  • Example 4 of the present invention Using the dispersion liquid and water of Example 4 of the present invention, the dispersion liquid and water were soaked into separate fabrics, and these fabrics were pressed against the metal plate on which the scales were adhered with a constant pressure, and the longitudinal direction The scale was washed by reciprocating 20 times, and the state after washing was observed. The results are shown in FIG.
  • the circle in the left side of FIG. 2 was washed using the dispersion liquid of Example 4 of the present invention, and it was recognized that the scale was successfully washed and removed.
  • the circle in the right side of FIG. 2 was washed with water, and it was recognized that the remaining washing of the scale was conspicuous.
  • the antibacterial agent of the present invention has an excellent cleaning effect on the metal plate and the like on which the scale is deposited.
  • Example 6 Using the 0.1 wt% antibacterial nanoparticle dispersion prepared in Example 1 (glycolic acid 0.05 wt%: Invention Example 1), a biofilm degradation test was performed. Water was used as a control.
  • Example 1 of the present invention Using the dispersion liquid and water of Example 1 of the present invention, 60 mL of the dispersion liquid and water were put into separate beakers (100 mL), biofilms of almost the same size were put into them, and a magnetic stirrer was used. Each beaker was stirred under conditions of 800 rpm ⁇ 24 hours. The state of decomposition of the biofilm piece after stirring was visually observed. The results are shown in FIG.
  • the inside of the left beaker in FIG. 3 was stirred using the dispersion liquid of Inventive Example 1, and it was recognized that the biofilm could be finely decomposed.
  • the inside of the beaker on the right side of FIG. 3 was stirred using water, and it was recognized that a large lump of biofilm was still conspicuous.
  • biofilm used as a hotbed of Legionella can be washed and decomposed by the antibacterial performance of the antibacterial agent of the present invention.
  • Example 7 In the 0.1 wt% antibacterial nanoparticle dispersion prepared in Example 1 (glycolic acid: Invention Example 1) and cyanoacrylate polymer particles conjugated with an amino acid (glycine) (Comparative Example 1), the respective particles The diameter was measured. The particle size was measured by a conventional method using a Zetasizer (Nano-ZS90 manufactured by Malvern). The result of the normal distribution of the particle diameter is shown in FIG.
  • the antibacterial nanoparticles in Inventive Example 1 were recognized to have a sharper distribution than the particles in Comparative Example 1 at about 100 to 300 nm. Therefore, the antibacterial agent of the present invention increases the transparency of the particle dispersion due to the small average particle diameter of the antibacterial nanoparticles and the sharpness of the normal distribution.
  • Example 8 In 200 g of purified water placed in a 500 mL container, 0.4 g of glycolic acid (organic acid: manufactured by Wako Pure Chemical Industries, Ltd.) and 2.0 mL of Tween 20 (manufactured by Sigma Aldrich Japan LLC) as a nonionic surfactant are dissolved. Furthermore, 2.0 g of isobutyl cyanoacrylate was dropped, and a polymerization reaction was performed using a magnetic stirrer (RS-1DN manufactured by AS ONE) under conditions of 600 rpm and 2 hours at room temperature. The reaction solution was filtered through a 5 ⁇ m-size membrane filter (manufactured by Sartorius: Mini Zalto) to prepare a 1.0 wt% antibacterial nanoparticle dispersion.
  • RS-1DN magnetic stirrer
  • the particle size of the antibacterial nanoparticles obtained at this time was measured by a conventional method using a Zetasizer (Nano-ZS90 manufactured by Malvern). The result of the normal distribution of the particle diameter is shown in FIG. As a result, the antibacterial nanoparticles in Invention Example 5 were recognized to have a sharp distribution at about 10 to 50 nm. The average particle diameter of the antibacterial nanoparticles of Invention Example 5 was 25 nm.
  • FIG. 6 shows a photograph of the antibacterial nanoparticle dispersion obtained in this example. According to this, it was recognized that the dispersion liquid of this example is in a state of high transparency. This is thought to be because the average particle diameter of the antibacterial nanoparticles obtained in this example was as fine as 25 nm, and thus the transparency was improved.
  • Example 9 In 200 g of purified water in a 500 mL container, 0.4 g of glycolic acid (organic acid: manufactured by Wako Pure Chemical Industries, Ltd.), 2.0 mL of Tween 20 (manufactured by Sigma Aldrich Japan LLC) as a nonionic surfactant, and anion As a surfactant, 0.2 mL of sodium alkylbenzene sulfonate (manufactured by Sigma Aldrich Japan GK) is dissolved, 2.0 g of isobutyl cyanoacrylate is further added dropwise, and a magnetic stirrer (RS-1DN manufactured by AS ONE) is used. The polymerization reaction was performed under conditions of 600 rpm and 2 hours at room temperature. The reaction solution was filtered through a 5 ⁇ m-size membrane filter (manufactured by Sartorius: Mini Zalto) to prepare a 1.0 wt% antibacterial nanoparticle dispersion.
  • glycolic acid organic acid: manufactured by Wako Pure Chemical Industries
  • the particle size of the antibacterial nanoparticles obtained at this time was measured by a conventional method using a Zetasizer (Nano-ZS90 manufactured by Malvern). The result of the normal distribution of the particle diameter is shown in FIG. As a result, the antibacterial nanoparticles in Invention Example 6 were recognized to have a sharp distribution at about 20 to 70 nm. The average particle diameter of the antibacterial nanoparticles of Invention Example 6 was 27 nm.
  • Example 10 The antibacterial nanoparticle dispersion prepared by adding a nonionic surfactant in Example 8 (Invention Example 5: average particle diameter 25 nm, 40 mg / L) and the antibacterial nanoparticle dispersion prepared in Example 1 (present)
  • Invention Example 1 The antibacterial effect on bacteria of the genus Bacillus subtilis ISW 1214 was examined for an average particle size of 155 nm and 40 mg / L. For the control, a dispersion of cyanoacrylate polymer particles of Comparative Example 1 was used.
  • the bacterial solution having a turbidity of about 0.05 was inoculated into the dispersions of Invention Examples 1 and 5 and Comparative Example 1, and then allowed to stand at 30 ° C. for about 8 hours to examine the turbidity of the dispersion. The results are shown in FIG.
  • the present invention can be used for an antibacterial agent containing cyanoacrylate polymer particles as an active ingredient and a method for producing the same.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Toxicology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne un agent antibactérien contenant, comme principe actif, des particules de polymère de cyanoacrylate qui comprennent, par au moins une certaine forme d'incorporation ou de mélange, un acide organique ; et un procédé de production d'un agent antibactérien qui est produit en effectuant une étape consistant à soumettre un monomère de cyanoacrylate à une polymérisation anionique, en présence du monomère de cyanoacrylate, d'un saccharide et d'un acide organique.
PCT/JP2015/075696 2014-09-11 2015-09-10 Agent antibactérien et procédé de fabrication d'un agent antibactérien Ceased WO2016039412A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2016547498A JPWO2016039412A1 (ja) 2014-09-11 2015-09-10 抗菌剤および抗菌剤の製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2014185387 2014-09-11
JP2014-185387 2014-09-11

Publications (1)

Publication Number Publication Date
WO2016039412A1 true WO2016039412A1 (fr) 2016-03-17

Family

ID=55459156

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2015/075696 Ceased WO2016039412A1 (fr) 2014-09-11 2015-09-10 Agent antibactérien et procédé de fabrication d'un agent antibactérien

Country Status (2)

Country Link
JP (1) JPWO2016039412A1 (fr)
WO (1) WO2016039412A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017081852A (ja) * 2015-10-28 2017-05-18 チカミミルテック株式会社 抗菌剤および抗菌剤の製造方法
WO2018193847A1 (fr) * 2017-04-18 2018-10-25 チカミミルテック株式会社 Inhibiteur de croissance d'algues et procédé d'inhibition de la croissance d'algues
JP2021116264A (ja) * 2020-01-27 2021-08-10 三菱鉛筆株式会社 抗菌粒子水分散体
JP2021116367A (ja) * 2020-01-27 2021-08-10 三菱鉛筆株式会社 筆記具用水性インク組成物
JP2023000739A (ja) * 2021-06-18 2023-01-04 三菱鉛筆株式会社 抗菌性粒子分散体

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005060273A (ja) * 2003-08-08 2005-03-10 Daiichi Seimou Co Ltd 有機酸製剤
WO2008126846A1 (fr) * 2007-04-09 2008-10-23 Yokohama City University Agent antibactérien actif contre les bactéries à gram positif résistantes à la vancomycine
WO2013108871A1 (fr) * 2012-01-19 2013-07-25 Shirotake Shoichi Agent antibactérien dirigé contre des bactéries provoquant une maladie des plantes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005060273A (ja) * 2003-08-08 2005-03-10 Daiichi Seimou Co Ltd 有機酸製剤
WO2008126846A1 (fr) * 2007-04-09 2008-10-23 Yokohama City University Agent antibactérien actif contre les bactéries à gram positif résistantes à la vancomycine
WO2013108871A1 (fr) * 2012-01-19 2013-07-25 Shirotake Shoichi Agent antibactérien dirigé contre des bactéries provoquant une maladie des plantes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GAO,Y. ET AL.: "In Vitro Release Kinetics of Antituberculosis Drugs from Nanoparticles Assessed Using a Modified Dissolution Apparatus", BIOMED RESEARCH INTERNATIONAL, 2013, [retrieved on 20151106] *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017081852A (ja) * 2015-10-28 2017-05-18 チカミミルテック株式会社 抗菌剤および抗菌剤の製造方法
WO2018193847A1 (fr) * 2017-04-18 2018-10-25 チカミミルテック株式会社 Inhibiteur de croissance d'algues et procédé d'inhibition de la croissance d'algues
JPWO2018193847A1 (ja) * 2017-04-18 2020-03-05 チカミミルテック株式会社 藻類増殖抑制剤および藻類の増殖を抑制する方法
JP7134442B2 (ja) 2017-04-18 2022-09-12 チカミミルテック株式会社 藻類増殖抑制剤および藻類の増殖を抑制する方法
JP2021116264A (ja) * 2020-01-27 2021-08-10 三菱鉛筆株式会社 抗菌粒子水分散体
JP2021116367A (ja) * 2020-01-27 2021-08-10 三菱鉛筆株式会社 筆記具用水性インク組成物
JP7324720B2 (ja) 2020-01-27 2023-08-10 三菱鉛筆株式会社 抗菌粒子水分散体
JP7454386B2 (ja) 2020-01-27 2024-03-22 三菱鉛筆株式会社 筆記具用水性インク組成物
JP2023000739A (ja) * 2021-06-18 2023-01-04 三菱鉛筆株式会社 抗菌性粒子分散体

Also Published As

Publication number Publication date
JPWO2016039412A1 (ja) 2017-07-13

Similar Documents

Publication Publication Date Title
Mohammed et al. Assessment of antimicrobial activity of chitosan/silver nanoparticles hydrogel and cryogel microspheres
Guo et al. Space-selective chemodynamic therapy of CuFe5O8 nanocubes for implant-related infections
Arabi Shamsabadi et al. Antimicrobial mode-of-action of colloidal Ti3C2T x MXene nanosheets
JP6423833B2 (ja) 抗菌性金属ナノ粒子の組成物および方法
Hendessi et al. Antibacterial sustained-release coatings from halloysite nanotubes/waterborne polyurethanes
Wei et al. Enhanced efficiency of antiseptics with sustained release from clay nanotubes
Dai et al. Functional silver nanoparticle as a benign antimicrobial agent that eradicates antibiotic-resistant bacteria and promotes wound healing
Smetana et al. Biocidal activity of nanocrystalline silver powders and particles
CN105793190B (zh) 氧化石墨烯纳米材料和阳离子季铵化壳聚糖的复合纳米材料
Guo et al. Functional silver nanocomposites as broad-spectrum antimicrobial and biofilm-disrupting agents
WO2016039412A1 (fr) Agent antibactérien et procédé de fabrication d'un agent antibactérien
Habimana et al. One particle, two targets: A combined action of functionalised gold nanoparticles, against Pseudomonas fluorescens biofilms
US20180027804A1 (en) Particle based enhanced removal for disinfection of surfaces
JP2016056481A (ja) 抗菌性シートおよび抗菌性シートの製造方法
Paunova-Krasteva et al. Destruction of Pseudomonas aeruginosa pre-formed biofilms by cationic polymer micelles bearing silver nanoparticles
Demarchi et al. Synthesis of Ag@ Fe2O3 nanocomposite based on O-carboxymethylchitosan with antimicrobial activity
JP2017081852A (ja) 抗菌剤および抗菌剤の製造方法
Alam et al. Highly sustained release of bactericides from complex coacervates
Peter et al. Biofilm inhibition on natural rubber by hydrophilic modification using carboxymethyl chitosan stabilised high energy faceted silver nanoparticles
Safavi et al. The study of nano silver (NS) antimicrobial activity and evaluation of using NS in tissue culture media
Azam et al. Enhanced Antibacterial Efficacy of Levilactobacillus Brevis Bacteriocin with Chitosan Nanoparticle Delivery
Liu et al. Enhanced antibacterial activity of polyphenol-bound microtopography by synergistic chemical and micro/nanomechanical effects
CN119911897B (zh) 一种针对植物卵菌病害的碳量子点及其制备方法和应用
Quyen et al. A simple and green preparation of chitosan/silver nanocomposites films and studying their antibacterial activity on Staphylococcus aureus and Escherichia coli
Krithiga et al. Synergistic antibacterial and antibiofilm activity of chemically synthesized silver nanoparticles against Pseudomonas aeruginosa

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15839412

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2016547498

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15839412

Country of ref document: EP

Kind code of ref document: A1