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WO2018217761A1 - Antimicrobial composition - Google Patents

Antimicrobial composition Download PDF

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Publication number
WO2018217761A1
WO2018217761A1 PCT/US2018/033905 US2018033905W WO2018217761A1 WO 2018217761 A1 WO2018217761 A1 WO 2018217761A1 US 2018033905 W US2018033905 W US 2018033905W WO 2018217761 A1 WO2018217761 A1 WO 2018217761A1
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Prior art keywords
composition
silver
vessel
solution
deionized water
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French (fr)
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Wiley William HITCHCOCK
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N59/00Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/16Heavy metals; Compounds thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/501,3-Diazoles; Hydrogenated 1,3-diazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18Liquid substances or solutions comprising solids or dissolved gases

Definitions

  • compositions comprising an antimicrobial and inhibit growth of microorganisms. Also disclosed herein are methods for reducing microorganisms.
  • microorganisms it is often advantageous and/or desirable to reduce microorganisms on a surface, on a human, and in the environment generally. For example, reducing microorganisms can reduce the likelihood a human's immune system becomes compromised resulting in illness and/or allergic reaction from contacting microorganisms in an environment.
  • compositions comprising 3-silver-l-methylimidazole.
  • a 3-silver-l-methylimidazole composition comprises silver particles, lactic acid, and 1-methylimidazole.
  • a composition further comprises sodium dodecyl sulfate (SDS).
  • a composition further comprises sodium tetraborate
  • compositions of the present invention may be any suitable material that comprises chitosan gel and 3-silver-l-methylimidazole.
  • a silver particle comprises elemental silver ions. Embodiments of compositions of the present invention may be
  • Embodiments of a composition of the present invention may be made by a variety of means, including by means of a method of the present invention.
  • the present invention provides a method of making a composition of 3 -silver- 1-methylimidazole comprising: combining metallic silver, 1-methylimidazole, and lactic acid.
  • a method may further comprise combining chitosan gel with the composition.
  • a method may further comprise combining chitosan gel and dimethyl sulfoxide (DMSO) with the composition.
  • DMSO dimethyl sulfoxide
  • a method may further comprise combining borax with the composition.
  • a method may further comprise combining SDS with the composition.
  • a composition of the present invention may be introduced to the environment, or applied to a surface in a variety of manners.
  • a method of the present invention for using a composition of the present invention comprises: introducing the composition to an environment.
  • the composition may be introduced in liquid, aerosol, powder, gel, or any other forms.
  • the composition may be introduced in a manner that allows the composition to disperse within the environment.
  • a method of the present invention for using a composition of the present invention comprises: applying the composition to a surface.
  • the surface may comprise a portion of a human or an animal, for example the skin.
  • the surface may comprise a portion of an article of manufacture, for example including, but not limited to, counter-tops, sinks, door knobs, walls, floor coverings, bathroom fixtures, furniture, and the like.
  • the present invention further provides methods for minimizing microorganisms.
  • a method for minimizing microorganisms comprises a method for using a composition of the present invention. In an embodiment, a method for minimizing
  • microorganisms comprises introducing a composition of the present invention into an environment.
  • the composition may be introduced in liquid, aerosol, powder, gel, or any other forms.
  • the composition may be introduced in a manner that allows the composition to disperse within the environment.
  • FIG. 1 shows Day 0 efficacy of a dispersible antimicrobial composition comprising sodium tetraborate decahydrate (borax) for a set of agar plates inoculated with bacteria and yeast.
  • FIG. 2 shows Day 85 efficacy of a dispersible antimicrobial composition comprising borax for a set of agar plates inoculated with bacteria and yeast.
  • FIG. 3 shows Day 0 efficacy of a dispersible antimicrobial composition comprising sodium dodecyl sulfate (SDS) for a set of agar plates inoculated with bacteria and yeast after a 24 hour incubation period.
  • SDS sodium dodecyl sulfate
  • FIG. 4 shows Day 0 efficacy of a dispersible antimicrobial composition comprising SDS for a set of agar plates inoculated with bacteria and yeast after a 48 hour incubation period.
  • FIG. 5 shows Day 180 efficacy of a dispersible antimicrobial composition comprising SDS for a set of agar plates inoculated with bacteria and yeast after a 24 hour incubation period.
  • FIG. 6 shows efficacy of a 1% SDS solution for a set of agar plates inoculated with bacteria and yeast.
  • FIG. 7 shows efficacy of a dispersible antimicrobial composition comprising SDS compared to conventional disinfectants.
  • Embodiments of the present invention include a silver-based antimicrobial composition, methods of producing the same, methods for using the same, and methods for minimizing microorganisms.
  • compositions of the present invention may be advantageous in minimizing and/or eliminating microorganisms.
  • Microorganisms, or microbes comprise microscopic organisms, which may be single-celled, multicellular, or intracellular.
  • Microorganisms as described herein may include, but are not limited to bacteria, yeast, virus, fungi, algae, and other microorganisms. Bacteria may be traditionally divided into two groups: Gram-positive and Gram-negative, based on their Gram stain retention. Gram-negative bacteria comprise Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Gram- positive bacteria comprise Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA). Yeast comprise Candida albicans. Virus comprises Herpes simplex, Influenza, and Rhinoviruses.
  • an antimicrobial composition of 3 -silver- 1-methylimidazole may comprise:
  • the composition may further comprise up to 0.3 wt.% sodium dodecyl sulfate (SDS).
  • SDS sodium dodecyl sulfate
  • Silver itself may have upwards of twenty modes of lethality to bacteria, which may reduce the susceptibility of silver to microbial resistance.
  • conventional silver- based compounds have a relatively short lifespan of chemical activity. This short lifespan limits potential uses of conventional silver-based compounds.
  • the compositions of 3-silver-l- methylimidazole described herein overcome many of these limitations by packaging silver ions in a form that may allow for extended shelf life and application stability.
  • the ionic bond between 1-methylimidazole and silver ions to form 3 -silver- 1- methylimidazole improves formulation stability and provides expanded antimicrobial properties.
  • combining silver ions with 1-methylimidazole to form 3 -silver- 1-methylimidazole may be advantageous to form a stable treatment for microorganisms, including drug-resistant bacteria.
  • 3 -silver- 1-methylimidazole may be effective as both an antibacterial and an antiviral agent.
  • 3 -silver- 1-methylimidazole has demonstrated standalone broad spectrum antibiotic properties by successfully substantially eliminating several types of bacteria as described in examples provided herein. Silver alone is also not known to be an antiviral agent; however, when ionically bound to 1-methylimidazole, the composition may exhibit very potent antiviral activity.
  • 3 -silver- 1-methylimidazole has demonstrated stand-alone antiviral properties by successfully substantially eliminating several types of viruses as described in examples provided herein. Not intending to be bound by theory, 3 -silver- 1-methylimidazole may not only interrupt the retroviral lifecycle of a virus, but may also prevent secondary opportunistic bacterial or yeast infections that may follow traditional treatments.
  • 3 -silver- 1-methylimidazole may be prepared in various formats or formulations, including gels and solutions, which may be dispersible or aerosolizable.
  • the composition described herein may be advantageous to conventional antimicrobials that may comprise quaternary amines, sodium hypochlorite, or alcohol.
  • a silver-based antimicrobial gel composition may comprise
  • composition may further comprise dimethyl sulfoxide (DMSO).
  • DMSO dimethyl sulfoxide
  • the composition may comprise 0.05 to 5 wt.%) 3 -silver- 1-methylimidazole, 0.5 to 2 wt.%> DMSO, and remainder chitosan gel, where chitosan gel comprises 0.1 to 5.0 wt.%> chitosan powder, 1 to 15 wt.%> glycerol, 0.1 to 5.0 wt.%) lactic acid, and the remainder deionized water.
  • the silver-based antimicrobial gel may be a topical healing antimicrobial gel composition.
  • a solution of antimicrobial composition may comprise
  • the composition may comprise 0.001 to 10 vol.%> 3- silver- 1-methylimidazole and remainder sodium dodecyl sulfate (SDS) solution, where SDS solution comprises 0.5 to 4 wt.%> SDS and the remainder deionized water.
  • SDS silver- 1-methylimidazole and remainder sodium dodecyl sulfate
  • the composition may be alkaline and may have a pH greater than 8. In certain embodiments, the composition may have a pH between 9 and 10, which may be desirable for safe use on metal, stone, and resin surfaces. In some embodiments, the composition may contain no corrosive active or inactive components. In some embodiments, the composition may contain no solvents or volatile organic compounds.
  • a composition of the present invention may be advantageously produced by a method of the present invention.
  • the methods disclosed herein may be used to prepare a silver- based antimicrobial composition.
  • a method of making silver-based 3-silver- 1-methylimidazole comprises adding deionized water to a silver powder in a vessel, mixing the composition until the silver is essentially wetted, adding 1-methylimidazole to the vessel, adding lactic acid to the vessel, and mixing the vessel until the composition is an essentially
  • a method of making silver-based antimicrobial 3 -silver- 1-methylimidazole comprises preparing a solution of SDS and deionized water in a first vessel, adding the SDS solution to a silver powder in a second vessel, mixing the composition until the silver is essentially wetted, adding 1-methylimidazole to the second vessel, adding lactic acid to the second vessel, and mixing the second vessel until the composition is an essentially homogeneous solution with substantially no clumps.
  • mixing may be performed by sonication, agitation, vortex, stirring, shaking, circulating, or other means.
  • the composition may be made in bulk and held for further processing.
  • a method of making a silver-based antimicrobial gel comprises combining chitosan powder, glycerol, and deionized water in a vessel, essentially dispersing the chitosan, adding lactic acid to the vessel, essentially dissolving the chitosan, and adding 3 -silver- 1-methylimidazole to the vessel.
  • the method of making a silver-based antimicrobial gel further comprises adding dimethyl sulfoxide (DMSO) to the vessel.
  • DMSO dimethyl sulfoxide
  • the composition may be stored to protect against exposure to ultraviolet light.
  • a method of making a silver-based antimicrobial solution comprises heating deionized water in a vessel, adding borax to the deionized water, essentially dissolving the borax, adding 3 -silver- 1-methylimidazole, and mixing the composition until the solution is essentially homogeneous.
  • the deionized water may be heated to between 30 to 50 °C.
  • a method of making a silver-based antimicrobial solution comprises combining deionized water and SDS, essentially dissolving the SDS, adding 3-silver-l-methylimidazole, and mixing the composition until the solution is essentially homogeneous.
  • the method involves mixing the solution during and/or after additions to the composition.
  • mixing may be performed by sonication, agitation, vortex, stirring, shaking, circulating, or other means.
  • the composition may be made in bulk and held for use in a UV protected container, such as an opaque or amber-colored container. Not intending to be bound by theory, the UV container may prevent the silver ions from returning to zero-valence metallic silver.
  • an article of manufacture comprising a composition of 3- silver- 1-methylimidazole.
  • the composition may comprise up to 10 vol.% 3-silver-l-methylimidazole and up to 4 wt.% borax.
  • the composition may comprise up to 10 vol.% 3-silver-l-methylimidazole and up to 4 vol.% SDS.
  • the composition may be capable of being dispersed as a mist.
  • the composition may comprise up to 5 wt.% 3-silver-l-methylimidazole, up to 5 wt.%) chitosan powder, and up to 15 wt.%> glycerol.
  • composition presented herein may be used independently or in conjunction with other applications to reduce microorganisms.
  • the composition may be evenly dispersed within the area to reduce or eliminate microorganisms.
  • the dispersion may be accomplished by means comprising misting, swabbing, and/or soaking the target area.
  • the target area may include, but is not limited to, counter-tops, sinks, door knobs, walls, floor coverings, bathroom fixtures, furniture, upholstery, and the like.
  • the composition may be topically applied to a surface to reduce or eliminate microorganisms.
  • the application may be accomplished by means comprising swabbing, and/or soaking the surface.
  • the surface may comprise a portion of a human or an animal, for example the skin.
  • the antimicrobial composition may be used in conjunction with other products.
  • These products include, but are not limited to, liquid soap, room
  • Example 1 Antimicrobial composition
  • An antimicrobial composition was prepared as follows. Silver powder was added to a vessel. Deionized water solution was added to the vessel, completely wetting the silver powder. Mixing by vortex or sonication was performed to thoroughly wet the silver. 1- methylimidazole was added to the vessel and then mixed by vortex. The addition of 1- methylimidazole was exothermic and was not performed with heating. Lactic acid was added to the vessel while mixing by vortex. The mixture was mixed by vortex until no clumps remained. The resulting antimicrobial composition of 3-silver-l-methylimidazole was a golden, clear liquid.
  • An antimicrobial composition was prepared as follows. A 1% working stock of
  • SDS was prepared in Vessel 1 by mixing SDS powder in deionized water and stirring until the SDS was dissolved.
  • Silver powder was added to Vessel 2. The SDS solution was added to Vessel 2, completely wetting the silver powder. Mixing by vortex or sonication was performed to thoroughly wet the silver.
  • 1-methylimidazole was added to Vessel 2 and then mixed by vortex. The addition of 1-methylimidazole was exothermic and was not performed with heating. Lactic acid was added to Vessel 2 while mixing by vortex. The mixture was mixed by vortex until no clumps remained.
  • the resulting antimicrobial composition of 3-silver-l-methylimidazole was a golden, clear liquid.
  • Example 3 Antimicrobial Composition in a gel
  • An antimicrobial composition was prepared with a chitosan gel base.
  • a chitosan gel was prepared as follows. Chitosan powder was added to a vessel. Glycerol and deionized water were added to the vessel. The solution was mixed to disperse the chitosan. Lactic acid was added to the vessel slowly while mixing. The mixture was mixed until the chitosan dissolved and the solution became clear. The resulting base was a thick, golden, transparent gel of 2% chitosan.
  • a silver-based antimicrobial gel composition was prepared by mixing the 2% chitosan gel with the antimicrobial composition of 3-silver-l-methylimidazole from Example 1.
  • the resulting wound healing composition was a milky-white gel.
  • the gel composition is not UV stable and should be stored in a UV protected container, such as an opaque or amber-colored container, to prevent the silver ions from returning to zero-valence metallic silver.
  • Example 4 Antimicrobial Composition for Wound Healing
  • An antimicrobial composition was prepared with a chitosan gel base.
  • a chitosan gel was prepared as follows. Chitosan powder was added to a vessel. Glycerol and deionized water were added to the vessel. The solution was mixed to disperse the chitosan. Lactic acid was added to the vessel slowly while mixing. The mixture was mixed until the chitosan dissolved and the solution became clear. The resulting base was a thick, golden, transparent gel of 2% chitosan.
  • a silver-based antimicrobial gel composition was prepared by preparing a mixture of the antimicrobial composition of 3 -silver- 1-methylimidazole from Example 1 with equal parts DMSO to increase the stability of the antimicrobial composition in the chitosan gel matrix.
  • the DMSO mixture was added the 2% chitosan gel.
  • the resulting silver-based antimicrobial gel composition was a milky-white gel.
  • the gel composition is not UV stable and should be stored in a UV protected container, such as an opaque or amber-colored container, to prevent the silver ions from returning to zero-valence metallic silver.
  • a cold sore caused by the Herpes Simplex virus was treated with the composition from Example 3.
  • the silver-based antimicrobial gel composition was applied 4 to 6 times per day upon the subject perceiving an outbreak, either by feeling or seeing the start of a cold sore.
  • Treatment with the gel composition shortened the cold sore cycle (development of cold sore to disappearance of cold sore) from a typical 1 to 2 week event down to a 3 to 5 day event.
  • Beginning treatment at the start of prodromal symptoms for the viral outbreak i.e., as soon as the lesion can be felt at the nerve endings (tingle) prior to the exit portal lesion being formed may be an optimal time to apply the topical gel composition to minimize virus replication.
  • MRS A infection A known Methicillin-resistant Staphylococcus aureus (MRS A) infection was treated with the composition from Example 3.
  • the silver-based antimicrobial gel composition was applied to the subject 3 times per day, directly to the site of the wound, with a bandage applied after each treatment. Treatment with the topical gel composition virtually eliminated the MRS A infection in the subject.
  • Example 8 Dispersible antimicrobial composition
  • dispersible antimicrobial composition To prepare the dispersible antimicrobial composition, deionized water was added to a vessel. SDS was added to the water with agitation. The solution was mixed until the SDS was visibility dissolved. A solution of 3 -silver- 1-methylimidazole was added, the solution having a concentration in the range of 0.001 to 1 wt. %. The vessel was gently mixed until the solution was visibility homogeneous. The resulting dispersible antimicrobial composition demonstrated stability of at least 1 year.
  • An efficacy assay was conducted to test the bactericidal/fungicidal activity of the dispersible antimicrobial composition from Examples 7 and 8.
  • the assay consisted of inoculating a lawn of bacteria/yeast from a newly grown broth culture onto their preferred agar media by dipping a sterile cotton swap into each broth, fully wetting the swab end, then swiping the swab back-and-forth from the top to the bottom of the plate, then turning the plate for a 1 ⁇ 4 turn and re-streaking from top to bottom again. This technique ensured total coverage of the inoculating bacteria/yeast across the face of the agar media.
  • the dish was then opened and a paper towel placed over the top of the plate to cover only half of the surface while not touching the agar surface, leaving the other half exposed.
  • This exposed half (the left side of the plate in the figures included herein) was then treated with 2-pumps from a spray bottle containing the dispersible antimicrobial composition, ensuring that the exposed half of the plate was saturated with the antimicrobial composition.
  • Each plate was treated using the same 2-pump criteria. All plates were then incubated "agar-down" overnight to allow the bacteria/yeast to fully grow. The bacterial plates were maintained at 37 °C; the yeast plates were maintained at 30 °C. For this test, a positive result was the treated half was clear of bacteria growth.
  • the control side may show full grown lawn of bacteria or reduced lawn growth depending on efficacy of the agent tested.
  • the results of the efficacy assay are provided in FIGS. 1 through 6.
  • the microorganisms tested are shown in the table below:
  • Example 7 The dispersible antimicrobial composition from Example 7 (comprising borax) showed very similar results on the Day 0 plate (FIG. 1) and the Day 85 plate (FIG. 2).
  • the antibiotic effect was slightly stronger in the Day 0 plates; however, both plates showed total kills for the treated sides of all five plates.
  • the sprayed areas were totally clear of any cell growth.
  • the kill effect spread or migrated to the untreated side of the plates killing a majority of the lawn bacteria. Only dispersed colony-forming unit (cfu) growth was visible in place of the lawn that was inoculated.
  • the media used for the assay was Trypticase Soy Agar (TSA) which contains sodium chloride (NaCl), which may neutralize silver ions to a much less effective antimicrobial form of silver, silver chloride (AgCl), which would not be expected to show an antibacterial effect in this assay.
  • TSA Trypticase Soy Agar
  • AgCl silver chloride
  • Conventional efficacy assays are performed using Muller-Hinton II Agar, which is void of NaCl to prevent media interference in testing antibiotics against challenge organisms.
  • FIG. 6 shows the control plates for the efficacy assay.
  • a 1 wt.% solution of SDS was used as a control for the assay. Comparing FIG. 6 to FIGS. 1 and 2 shows the effectiveness of the antimicrobial composition. Only plates 2, 3, and 5 showed any reduction of the microorganisms with the control 1% SDS solution (FIG. 6), whereas all plates in FIGS. 1 and 2 showed effective reduction in the microorganisms.
  • the performance of dispersible antimicrobial composition from Example 7 (comprising borax) showed greater broad-spectrum effectiveness than the 1% SDS solution alone.
  • the dispersible antimicrobial composition from Example 7 (comprising borax) still showed strong antimicrobial effectiveness after 85 days of shelf-life (FIG. 2).
  • the dispersible antimicrobial composition from Example 8 (comprising SDS) showed a high level of effectiveness on the treated side (left side) of the plates (FIGS. 3, 4, and 5).
  • the antimicrobial composition showed such a high level of effectiveness that it was difficult to find bacterial growth on the untreated side of most of the test plates.
  • the only plates that showed any growth at all were the Pseudomonas a. (plate 4, FIGS. 3 and 4) and Staph, aureus (plate 5, FIGS. 3 and 4).
  • the composition had a high level of migration efficacy at Day 180.
  • SDS was compatible with the antimicrobial composition and allowed for high effectiveness with the 1 vol.% 3 -silver- 1-methylimidazole formulation, even after 180 days post-treatment.
  • the performance of dispersible antimicrobial composition from Example 8 demonstrated long-term chemical stability and antimicrobial efficacy of using SDS as an additive partner for 3 -silver- 1-methylimidazole.
  • An efficacy assay was conducted to test the bactericidal/fungicidal activity of the dispersible antimicrobial composition from Example 8 (comprising SDS) compared to conventional disinfectants, sodium hypochlorite (10% bleach solution) and ethanol (70% solution).
  • the assay consisted of inoculating a lawn of bacteria/yeast from a newly grown broth culture onto their preferred agar media by dipping a cotton swap into each broth, fully wetting the swab end, then swiping the swab back-and-forth from the top to the bottom of the plate, then turning the plate for a 1 ⁇ 4 turn and re-streaking from top to bottom again.
  • This technique ensured total coverage of the inoculating bacteria/yeast across the face of the agar media.
  • the dish was then opened and a paper towel placed over the top of the plate to cover only half of the surface while not touching the agar surface, leaving the other half exposed.
  • This exposed half (the left side of the plate in the figures included herein) was then treated with 2-pumps from a spray bottle containing the treatment solution, ensuring that the exposed half of the plate was saturated with the antimicrobial composition.
  • Each plate was treated using the same 2-pump criteria. All plates were then incubated "agar-down" overnight to allow the bacteria/yeast to fully grow.
  • the bacterial plates were maintained at 37 °C; the yeast plates were maintained at 30 °C.
  • the dispersible antimicrobial composition showed a high level of effectiveness on the treated side (left side) of all the plates (FIG. 7).
  • the antimicrobial composition showed such a high level of effectiveness that it was difficult to find bacterial growth on the untreated side of test plate 3.
  • the composition Comparing the silver-based antimicrobial composition comprising 3-silver-l- methylimidazole to the sodium hypochlorite solution, the composition showed substantially equivalent effectiveness on the treated side of the plates, but exhibited greater migration into the untreated side of the plate than the sodium hypochlorite solution. Comparing the composition to the ethanol, the ethanol exhibited virtually no kill of the microbes on plates 2 and 5, minimal kill in plate 3 as shown by the disruption of the bacterial lawn in the lower left corner, and moderate effectiveness in plates 1 and 4. Thus, the silver-based antimicrobial composition showed superior antimicrobial effectiveness as compared to conventional disinfectant agents, sodium hypochlorite and ethanol.
  • any reference to methods, compositions, or articles is understood as a reference to each of those methods, compositions, or articles disjunctively (e.g., "Illustrative embodiment 1-4 is understood as illustrative embodiment 1, 2, 3, or 4.”).
  • Illustrative embodiment 1 is an antimicrobial composition comprising about:
  • Illustrative embodiment 2 is the composition of any preceding or subsequent illustrative embodiment, further comprising about 0.3 wt.% sodium dodecyl sulfate.
  • Illustrative embodiment 3 is a silver-based antimicrobial gel composition comprising about: 0.05 to 5 wt.% of the composition of any of any preceding or subsequent illustrative embodiment; and a chitosan gel, wherein the chitosan gel comprises about 0.1 to 5 wt.%) chitosan powder, 1 to 15 wt.%> glycerol, 0.1 to 5 wt.%> lactic acid, and deionized water.
  • Illustrative embodiment 4 is the composition of any preceding or subsequent illustrative embodiment, further comprising about 0.5 to 2 wt.%> dimethyl sulfoxide.
  • Illustrative embodiment 5 is an antimicrobial solution comprising about: 0.001 to
  • the composition of of any preceding or subsequent illustrative embodiment and a sodium tetraborate decahydrate solution, wherein the sodium tetraborate decahydrate solution comprises about 0.5 to 4 wt.%> sodium tetraborate decahydrate and deionized water.
  • Illustrative embodiment 6 is an antimicrobial solution comprising about: 0.001 to
  • composition of any of any preceding or subsequent illustrative embodiment; and a sodium dodecyl sulfate solution, wherein the sodium dodecyl sulfate solution comprises about 0.5 to 4 wt.%) sodium dodecyl sulfate and deionized water.
  • Illustrative embodiment 7 is the composition of any preceding or subsequent illustrative embodiment, wherein the composition is capable of forming a mist.
  • Illustrative embodiment 8 is the composition of any preceding or subsequent illustrative embodiment, wherein the composition has a pH between 8 and 10.
  • Illustrative embodiment 9 is a method of making an antimicrobial composition comprising: adding deionized water to a silver powder in a vessel; mixing the composition until the silver is essentially wetted; adding 1-methylimidazole to the vessel; adding lactic acid to the vessel; and mixing the vessel until the composition is an essentially homogeneous solution with substantially no clumps.
  • Illustrative embodiment 10 is the method of any preceding or subsequent illustrative embodiment, further comprising: preparing a solution of sodium dodecyl sulfate and deionized water in a first vessel; and adding the sodium dodecyl sulfate solution to the silver powder of any preceding or subsequent illustrative embodiment.
  • Illustrative embodiment 11 is a method of making a silver-based antimicrobial gel comprising: combining chitosan powder, glycerol, and deionized water in a vessel; essentially dispersing the chitosan by mixing; adding lactic acid to the vessel; essentially dissolving the chitosan; and adding the composition from any preceding or subsequent illustrative embodiment to the vessel.
  • Illustrative embodiment 12 is the method of any preceding or subsequent illustrative embodiment, further comprising adding dimethyl sulfoxide to the vessel.
  • Illustrative embodiment 13 is a method of making a silver-based antimicrobial solution comprising: heating deionized water in a vessel; adding sodium tetraborate decahydrate to the deionized water; essentially dissolving the sodium tetraborate decahydrate; adding the composition from any preceding or subsequent illustrative embodiment to the vessel; and mixing the vessel until the solution is essentially homogeneous.
  • Illustrative embodiment 14 is the method of any preceding or subsequent illustrative embodiment, wherein the deionized water is heated to between 30°C and 50°C.
  • Illustrative embodiment 15 is a method of making a silver-based antimicrobial solution comprising: combining deionized water and sodium dodecyl sulfate in a vessel;
  • Illustrative embodiment 16 is the method of any preceding or subsequent illustrative embodiment, wherein mixing comprises agitating, sonicating, vortexing, stirring, shaking, and circulating.
  • Illustrative embodiment 17 is an article of manufacture comprising the composition of any preceding or subsequent illustrative embodiment.
  • Illustrative embodiment 18 is the article of manufacture of any preceding or subsequent illustrative embodiment, wherein the composition is capable of being dispersed as a mist.
  • Illustrative embodiment 19 is a method for using the composition of any preceding or subsequent illustrative embodiment to minimize microorganisms comprising introducing the composition to an environment.
  • Illustrative embodiment 20 is the method of any preceding or subsequent illustrative embodiment, wherein the composition is applied to a surface, wherein said surface comprises a living being or article of manufacture.
  • Illustrative embodiment 21 is the method of any preceding or subsequent illustrative embodiment, wherein the living being comprises a portion of a human or an animal.
  • Illustrative embodiment 22 is the method of any preceding or subsequent illustrative embodiment, wherein article of manufacture comprises counter-tops, sinks, door knobs, walls, floor coverings, bathroom fixtures, furniture, and upholstery.
  • Illustrative embodiment 23 is the method of any preceding or subsequent illustrative embodiment, wherein the composition is introduced in forms comprising at least one of a liquid, an aerosol, a gel, or a powder.

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Abstract

An antimicrobial composition comprising silver and 1-methylimidazole is disclosed, together with methods of making and using the same, and methods for reducing microorganisms.

Description

ANTIMICROBIAL COMPOSITION
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 62/510,039, filed on May 23, 2017, which is incorporated herein by reference in its entirety.
FIELD
[0002] Described herein are compositions, methods for producing compositions, and methods of using compositions. In embodiments, the compositions comprise an antimicrobial and inhibit growth of microorganisms. Also disclosed herein are methods for reducing microorganisms.
BACKGROUND
[0003] It is often advantageous and/or desirable to reduce microorganisms on a surface, on a human, and in the environment generally. For example, reducing microorganisms can reduce the likelihood a human's immune system becomes compromised resulting in illness and/or allergic reaction from contacting microorganisms in an environment.
SUMMARY
[0004] Described herein are compositions comprising 3-silver-l-methylimidazole. In embodiments, a 3-silver-l-methylimidazole composition comprises silver particles, lactic acid, and 1-methylimidazole. In some embodiments, a composition further comprises sodium dodecyl sulfate (SDS). In embodiments, a composition further comprises sodium tetraborate
decahydrate, commonly known as borax. In some embodiments, a composition comprises chitosan gel and 3-silver-l-methylimidazole. In an embodiment, a silver particle comprises elemental silver ions. Embodiments of compositions of the present invention may be
advantageous in minimizing and/or eliminating microorganisms.
[0005] Embodiments of a composition of the present invention may be made by a variety of means, including by means of a method of the present invention. In an embodiment, the present invention provides a method of making a composition of 3 -silver- 1-methylimidazole comprising: combining metallic silver, 1-methylimidazole, and lactic acid. In an embodiment, a method may further comprise combining chitosan gel with the composition. In an embodiment, a method may further comprise combining chitosan gel and dimethyl sulfoxide (DMSO) with the composition. In an embodiment, a method may further comprise combining borax with the composition. In an embodiment, a method may further comprise combining SDS with the composition.
[0006] A composition of the present invention may be introduced to the environment, or applied to a surface in a variety of manners. In an embodiment, a method of the present invention for using a composition of the present invention comprises: introducing the composition to an environment. In embodiments, the composition may be introduced in liquid, aerosol, powder, gel, or any other forms. In an embodiment, the composition may be introduced in a manner that allows the composition to disperse within the environment.
[0007] In another embodiment, a method of the present invention for using a composition of the present invention comprises: applying the composition to a surface. In an embodiment, the surface may comprise a portion of a human or an animal, for example the skin. In an embodiment the surface may comprise a portion of an article of manufacture, for example including, but not limited to, counter-tops, sinks, door knobs, walls, floor coverings, bathroom fixtures, furniture, and the like.
[0008] The present invention further provides methods for minimizing microorganisms.
In an embodiment, a method for minimizing microorganisms comprises a method for using a composition of the present invention. In an embodiment, a method for minimizing
microorganisms comprises introducing a composition of the present invention into an environment. In embodiments, the composition may be introduced in liquid, aerosol, powder, gel, or any other forms. In an embodiment, the composition may be introduced in a manner that allows the composition to disperse within the environment.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The invention may be further understood by reference to the following non- limiting figures. [0010] FIG. 1 shows Day 0 efficacy of a dispersible antimicrobial composition comprising sodium tetraborate decahydrate (borax) for a set of agar plates inoculated with bacteria and yeast.
[0011] FIG. 2 shows Day 85 efficacy of a dispersible antimicrobial composition comprising borax for a set of agar plates inoculated with bacteria and yeast.
[0012] FIG. 3 shows Day 0 efficacy of a dispersible antimicrobial composition comprising sodium dodecyl sulfate (SDS) for a set of agar plates inoculated with bacteria and yeast after a 24 hour incubation period.
[0013] FIG. 4 shows Day 0 efficacy of a dispersible antimicrobial composition comprising SDS for a set of agar plates inoculated with bacteria and yeast after a 48 hour incubation period.
[0014] FIG. 5 shows Day 180 efficacy of a dispersible antimicrobial composition comprising SDS for a set of agar plates inoculated with bacteria and yeast after a 24 hour incubation period.
[0015] FIG. 6 shows efficacy of a 1% SDS solution for a set of agar plates inoculated with bacteria and yeast.
[0016] FIG. 7 shows efficacy of a dispersible antimicrobial composition comprising SDS compared to conventional disinfectants.
DETAILED DESCRIPTION OF THE INVENTION
[0017] Embodiments of the present invention include a silver-based antimicrobial composition, methods of producing the same, methods for using the same, and methods for minimizing microorganisms.
[0018] Embodiments of compositions of the present invention may be advantageous in minimizing and/or eliminating microorganisms. Microorganisms, or microbes, comprise microscopic organisms, which may be single-celled, multicellular, or intracellular.
Microorganisms as described herein may include, but are not limited to bacteria, yeast, virus, fungi, algae, and other microorganisms. Bacteria may be traditionally divided into two groups: Gram-positive and Gram-negative, based on their Gram stain retention. Gram-negative bacteria comprise Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Gram- positive bacteria comprise Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA). Yeast comprise Candida albicans. Virus comprises Herpes simplex, Influenza, and Rhinoviruses.
[0019] The invention may be embodied in a variety of ways. In certain embodiments, an antimicrobial composition of 3 -silver- 1-methylimidazole may comprise:
[0020] 0.5 to 10 wt.% silver particles;
[0021] 20 to 30 wt.% deionized water;
[0022] 40 to 60 wt.% 1-methylimidazole; and
[0023] 10 to 25 wt.% lactic acid.
In some embodiments, the composition may further comprise up to 0.3 wt.% sodium dodecyl sulfate (SDS).
[0024] Silver itself may have upwards of twenty modes of lethality to bacteria, which may reduce the susceptibility of silver to microbial resistance. However, conventional silver- based compounds have a relatively short lifespan of chemical activity. This short lifespan limits potential uses of conventional silver-based compounds. The compositions of 3-silver-l- methylimidazole described herein overcome many of these limitations by packaging silver ions in a form that may allow for extended shelf life and application stability. Not intending to be bound by theory, the ionic bond between 1-methylimidazole and silver ions to form 3 -silver- 1- methylimidazole improves formulation stability and provides expanded antimicrobial properties. Thus, combining silver ions with 1-methylimidazole to form 3 -silver- 1-methylimidazole may be advantageous to form a stable treatment for microorganisms, including drug-resistant bacteria.
[0025] As described in examples herein, 3 -silver- 1-methylimidazole may be effective as both an antibacterial and an antiviral agent. 3 -silver- 1-methylimidazole has demonstrated standalone broad spectrum antibiotic properties by successfully substantially eliminating several types of bacteria as described in examples provided herein. Silver alone is also not known to be an antiviral agent; however, when ionically bound to 1-methylimidazole, the composition may exhibit very potent antiviral activity. 3 -silver- 1-methylimidazole has demonstrated stand-alone antiviral properties by successfully substantially eliminating several types of viruses as described in examples provided herein. Not intending to be bound by theory, 3 -silver- 1-methylimidazole may not only interrupt the retroviral lifecycle of a virus, but may also prevent secondary opportunistic bacterial or yeast infections that may follow traditional treatments.
[0026] 3 -silver- 1-methylimidazole may be prepared in various formats or formulations, including gels and solutions, which may be dispersible or aerosolizable. The composition described herein may be advantageous to conventional antimicrobials that may comprise quaternary amines, sodium hypochlorite, or alcohol.
[0027] In some embodiments, a silver-based antimicrobial gel composition may comprise
0.05 to 5 wt.% 3 -silver- 1-methylimidazole and remainder chitosan gel, where chitosan gel comprises 0.1 to 5 wt.% chitosan powder, 1 to 15 wt.% glycerol, 0.1 to 5 wt.% lactic acid, and the remainder deionized water. In some embodiments, the composition may further comprise dimethyl sulfoxide (DMSO). For example, in one embodiment, the composition may comprise 0.05 to 5 wt.%) 3 -silver- 1-methylimidazole, 0.5 to 2 wt.%> DMSO, and remainder chitosan gel, where chitosan gel comprises 0.1 to 5.0 wt.%> chitosan powder, 1 to 15 wt.%> glycerol, 0.1 to 5.0 wt.%) lactic acid, and the remainder deionized water. In some embodiments, the silver-based antimicrobial gel may be a topical healing antimicrobial gel composition.
[0028] Functionalizing 3 -silver- 1-methylimidazole into a stable and effective disinfectant spray or aerosol would be advantageous. Many conventional sprays and aerosols utilize deionized water or ethanol as a base. However, these bases may not effectively stabilize 3- silver- 1-methylimidazole. The use of a stabilizing agent, such as surfactants or detergents, that do not interfere with the overall efficacy of 3 -silver- 1-methylimidazole may aid functionalizing 3 -silver- 1-methylimidazole into a stable formulation that maintains its antimicrobial properties.
[0029] In some embodiments, a solution of antimicrobial composition may comprise
0.001 to 10 vol.%) 3 -silver- 1-methylimidazole and remainder sodium tetraborate decahydrate (borax) solution, where borax solution comprises 0.5 to 4 wt.%> borax and the remainder deionized water. In some embodiments, the composition may comprise 0.001 to 10 vol.%> 3- silver- 1-methylimidazole and remainder sodium dodecyl sulfate (SDS) solution, where SDS solution comprises 0.5 to 4 wt.%> SDS and the remainder deionized water.
[0030] In some embodiments, the composition may be alkaline and may have a pH greater than 8. In certain embodiments, the composition may have a pH between 9 and 10, which may be desirable for safe use on metal, stone, and resin surfaces. In some embodiments, the composition may contain no corrosive active or inactive components. In some embodiments, the composition may contain no solvents or volatile organic compounds.
[0031] A composition of the present invention may be advantageously produced by a method of the present invention. The methods disclosed herein may be used to prepare a silver- based antimicrobial composition. In an embodiment, a method of making silver-based 3-silver- 1-methylimidazole comprises adding deionized water to a silver powder in a vessel, mixing the composition until the silver is essentially wetted, adding 1-methylimidazole to the vessel, adding lactic acid to the vessel, and mixing the vessel until the composition is an essentially
homogeneous solution with substantially no clumps. In an embodiment, a method of making silver-based antimicrobial 3 -silver- 1-methylimidazole comprises preparing a solution of SDS and deionized water in a first vessel, adding the SDS solution to a silver powder in a second vessel, mixing the composition until the silver is essentially wetted, adding 1-methylimidazole to the second vessel, adding lactic acid to the second vessel, and mixing the second vessel until the composition is an essentially homogeneous solution with substantially no clumps. In some embodiments, mixing may be performed by sonication, agitation, vortex, stirring, shaking, circulating, or other means. In some embodiments, the composition may be made in bulk and held for further processing.
[0032] The methods disclosed herein may be used to prepare a silver-based antimicrobial composition in the form of a gel. In an embodiment, a method of making a silver-based antimicrobial gel comprises combining chitosan powder, glycerol, and deionized water in a vessel, essentially dispersing the chitosan, adding lactic acid to the vessel, essentially dissolving the chitosan, and adding 3 -silver- 1-methylimidazole to the vessel. In some embodiments, the method of making a silver-based antimicrobial gel further comprises adding dimethyl sulfoxide (DMSO) to the vessel. In some embodiments, the composition may be stored to protect against exposure to ultraviolet light.
[0033] The methods disclosed herein may be used to prepare a silver-based antimicrobial composition in the form of a solution. In an embodiment, a method of making a silver-based antimicrobial solution comprises heating deionized water in a vessel, adding borax to the deionized water, essentially dissolving the borax, adding 3 -silver- 1-methylimidazole, and mixing the composition until the solution is essentially homogeneous. In some embodiments, the deionized water may be heated to between 30 to 50 °C. In an embodiment, a method of making a silver-based antimicrobial solution comprises combining deionized water and SDS, essentially dissolving the SDS, adding 3-silver-l-methylimidazole, and mixing the composition until the solution is essentially homogeneous. In some embodiments, the method involves mixing the solution during and/or after additions to the composition. In some embodiments, mixing may be performed by sonication, agitation, vortex, stirring, shaking, circulating, or other means. In some embodiments, the composition may be made in bulk and held for use in a UV protected container, such as an opaque or amber-colored container. Not intending to be bound by theory, the UV container may prevent the silver ions from returning to zero-valence metallic silver.
[0034] Also described herein is an article of manufacture comprising a composition of 3- silver- 1-methylimidazole. In some embodiments, the composition may comprise up to 10 vol.% 3-silver-l-methylimidazole and up to 4 wt.% borax. In some embodiments, the composition may comprise up to 10 vol.% 3-silver-l-methylimidazole and up to 4 vol.% SDS. In some embodiments, the composition may be capable of being dispersed as a mist. In some
embodiments, the composition may comprise up to 5 wt.% 3-silver-l-methylimidazole, up to 5 wt.%) chitosan powder, and up to 15 wt.%> glycerol.
[0035] The composition presented herein may be used independently or in conjunction with other applications to reduce microorganisms. In some embodiments designed for independent use, the composition may be evenly dispersed within the area to reduce or eliminate microorganisms. The dispersion may be accomplished by means comprising misting, swabbing, and/or soaking the target area. The target area may include, but is not limited to, counter-tops, sinks, door knobs, walls, floor coverings, bathroom fixtures, furniture, upholstery, and the like.
[0036] In some embodiments designed for independent use, the composition may be topically applied to a surface to reduce or eliminate microorganisms. The application may be accomplished by means comprising swabbing, and/or soaking the surface. In an embodiment, the surface may comprise a portion of a human or an animal, for example the skin.
[0037] In other embodiments, the antimicrobial composition may be used in conjunction with other products. These products include, but are not limited to, liquid soap, room
deodorizing spray, surface and household cleaners, laundry detergents, bandages, lip balm, and other products where antimicrobial properties would be desirable. Example 1 : Antimicrobial composition
Figure imgf000009_0001
[0038] An antimicrobial composition was prepared as follows. Silver powder was added to a vessel. Deionized water solution was added to the vessel, completely wetting the silver powder. Mixing by vortex or sonication was performed to thoroughly wet the silver. 1- methylimidazole was added to the vessel and then mixed by vortex. The addition of 1- methylimidazole was exothermic and was not performed with heating. Lactic acid was added to the vessel while mixing by vortex. The mixture was mixed by vortex until no clumps remained. The resulting antimicrobial composition of 3-silver-l-methylimidazole was a golden, clear liquid.
Example 2: Antimicrobial composition
Figure imgf000009_0002
[0039] An antimicrobial composition was prepared as follows. A 1% working stock of
SDS was prepared in Vessel 1 by mixing SDS powder in deionized water and stirring until the SDS was dissolved. [0040] Silver powder was added to Vessel 2. The SDS solution was added to Vessel 2, completely wetting the silver powder. Mixing by vortex or sonication was performed to thoroughly wet the silver. 1-methylimidazole was added to Vessel 2 and then mixed by vortex. The addition of 1-methylimidazole was exothermic and was not performed with heating. Lactic acid was added to Vessel 2 while mixing by vortex. The mixture was mixed by vortex until no clumps remained. The resulting antimicrobial composition of 3-silver-l-methylimidazole was a golden, clear liquid.
Example 3 : Antimicrobial Composition in a gel
Figure imgf000010_0001
[0041] An antimicrobial composition was prepared with a chitosan gel base. A chitosan gel was prepared as follows. Chitosan powder was added to a vessel. Glycerol and deionized water were added to the vessel. The solution was mixed to disperse the chitosan. Lactic acid was added to the vessel slowly while mixing. The mixture was mixed until the chitosan dissolved and the solution became clear. The resulting base was a thick, golden, transparent gel of 2% chitosan.
[0042] A silver-based antimicrobial gel composition was prepared by mixing the 2% chitosan gel with the antimicrobial composition of 3-silver-l-methylimidazole from Example 1. The resulting wound healing composition was a milky-white gel. The gel composition is not UV stable and should be stored in a UV protected container, such as an opaque or amber-colored container, to prevent the silver ions from returning to zero-valence metallic silver. Example 4: Antimicrobial Composition for Wound Healing
Figure imgf000011_0001
[0043] An antimicrobial composition was prepared with a chitosan gel base. A chitosan gel was prepared as follows. Chitosan powder was added to a vessel. Glycerol and deionized water were added to the vessel. The solution was mixed to disperse the chitosan. Lactic acid was added to the vessel slowly while mixing. The mixture was mixed until the chitosan dissolved and the solution became clear. The resulting base was a thick, golden, transparent gel of 2% chitosan.
[0044] A silver-based antimicrobial gel composition was prepared by preparing a mixture of the antimicrobial composition of 3 -silver- 1-methylimidazole from Example 1 with equal parts DMSO to increase the stability of the antimicrobial composition in the chitosan gel matrix. The DMSO mixture was added the 2% chitosan gel. The resulting silver-based antimicrobial gel composition was a milky-white gel. The gel composition is not UV stable and should be stored in a UV protected container, such as an opaque or amber-colored container, to prevent the silver ions from returning to zero-valence metallic silver.
Example 5: Herpes treatment
[0045] A cold sore caused by the Herpes Simplex virus was treated with the composition from Example 3. The silver-based antimicrobial gel composition was applied 4 to 6 times per day upon the subject perceiving an outbreak, either by feeling or seeing the start of a cold sore. Treatment with the gel composition shortened the cold sore cycle (development of cold sore to disappearance of cold sore) from a typical 1 to 2 week event down to a 3 to 5 day event. Beginning treatment at the start of prodromal symptoms for the viral outbreak, i.e., as soon as the lesion can be felt at the nerve endings (tingle) prior to the exit portal lesion being formed may be an optimal time to apply the topical gel composition to minimize virus replication.
Example 6: MRS A treatment
[0046] A known Methicillin-resistant Staphylococcus aureus (MRS A) infection was treated with the composition from Example 3. The silver-based antimicrobial gel composition was applied to the subject 3 times per day, directly to the site of the wound, with a bandage applied after each treatment. Treatment with the topical gel composition virtually eliminated the MRS A infection in the subject.
Example 7: Dispersible antimicrobial composition
Figure imgf000012_0001
[0047] To prepare the dispersible antimicrobial composition, deionized water was added to a vessel and heated to 30-50°C with agitation. Borax was added to the heated water with agitation. The solution was mixed until the Borax was visibility dissolved. A solution of 3- silver- 1-methylimidazole was added, the solution having a concentration in the range of 0.001 to 1 wt. %. The vessel was agitated until the solution was visibility homogeneous. The resulting dispersible antimicrobial composition had demonstrated efficacy and stability of at least 85 days.
Example 8: Dispersible antimicrobial composition
Figure imgf000012_0002
To prepare the dispersible antimicrobial composition, deionized water was added to a vessel. SDS was added to the water with agitation. The solution was mixed until the SDS was visibility dissolved. A solution of 3 -silver- 1-methylimidazole was added, the solution having a concentration in the range of 0.001 to 1 wt. %. The vessel was gently mixed until the solution was visibility homogeneous. The resulting dispersible antimicrobial composition demonstrated stability of at least 1 year.
Example 9: Efficacy Assay
[0048] An efficacy assay was conducted to test the bactericidal/fungicidal activity of the dispersible antimicrobial composition from Examples 7 and 8. The assay consisted of inoculating a lawn of bacteria/yeast from a newly grown broth culture onto their preferred agar media by dipping a sterile cotton swap into each broth, fully wetting the swab end, then swiping the swab back-and-forth from the top to the bottom of the plate, then turning the plate for a ¼ turn and re-streaking from top to bottom again. This technique ensured total coverage of the inoculating bacteria/yeast across the face of the agar media. The dish was then opened and a paper towel placed over the top of the plate to cover only half of the surface while not touching the agar surface, leaving the other half exposed. This exposed half (the left side of the plate in the figures included herein) was then treated with 2-pumps from a spray bottle containing the dispersible antimicrobial composition, ensuring that the exposed half of the plate was saturated with the antimicrobial composition. Each plate was treated using the same 2-pump criteria. All plates were then incubated "agar-down" overnight to allow the bacteria/yeast to fully grow. The bacterial plates were maintained at 37 °C; the yeast plates were maintained at 30 °C. For this test, a positive result was the treated half was clear of bacteria growth. The control side may show full grown lawn of bacteria or reduced lawn growth depending on efficacy of the agent tested. The results of the efficacy assay are provided in FIGS. 1 through 6. The microorganisms tested are shown in the table below:
Figure imgf000013_0001
4 Pseudomonas aeruginosa Gram (-) bacteria ATCC-9027
5 Staphylococcus aureus Gram (+) bacteria ATCC-6538
[0049] The dispersible antimicrobial composition from Example 7 (comprising borax) showed very similar results on the Day 0 plate (FIG. 1) and the Day 85 plate (FIG. 2). By way of comparison, the antibiotic effect was slightly stronger in the Day 0 plates; however, both plates showed total kills for the treated sides of all five plates. The sprayed areas were totally clear of any cell growth. For Plates 1 and 3, the kill effect spread or migrated to the untreated side of the plates killing a majority of the lawn bacteria. Only dispersed colony-forming unit (cfu) growth was visible in place of the lawn that was inoculated.
[0050] The media used for the assay was Trypticase Soy Agar (TSA) which contains sodium chloride (NaCl), which may neutralize silver ions to a much less effective antimicrobial form of silver, silver chloride (AgCl), which would not be expected to show an antibacterial effect in this assay. The ability of the dispersible antimicrobial composition to diffuse in this media and maintain its antimicrobial effect shows the stability of the composition. Conventional efficacy assays are performed using Muller-Hinton II Agar, which is void of NaCl to prevent media interference in testing antibiotics against challenge organisms.
[0051] FIG. 6 shows the control plates for the efficacy assay. A 1 wt.% solution of SDS was used as a control for the assay. Comparing FIG. 6 to FIGS. 1 and 2 shows the effectiveness of the antimicrobial composition. Only plates 2, 3, and 5 showed any reduction of the microorganisms with the control 1% SDS solution (FIG. 6), whereas all plates in FIGS. 1 and 2 showed effective reduction in the microorganisms. Thus, the performance of dispersible antimicrobial composition from Example 7 (comprising borax) showed greater broad-spectrum effectiveness than the 1% SDS solution alone. Furthermore, the dispersible antimicrobial composition from Example 7 (comprising borax) still showed strong antimicrobial effectiveness after 85 days of shelf-life (FIG. 2).
[0052] The dispersible antimicrobial composition from Example 8 (comprising SDS) showed a high level of effectiveness on the treated side (left side) of the plates (FIGS. 3, 4, and 5). The antimicrobial composition showed such a high level of effectiveness that it was difficult to find bacterial growth on the untreated side of most of the test plates. The only plates that showed any growth at all were the Pseudomonas a. (plate 4, FIGS. 3 and 4) and Staph, aureus (plate 5, FIGS. 3 and 4). As shown in FIG. 5, the composition had a high level of migration efficacy at Day 180. SDS was compatible with the antimicrobial composition and allowed for high effectiveness with the 1 vol.% 3 -silver- 1-methylimidazole formulation, even after 180 days post-treatment. Thus, the performance of dispersible antimicrobial composition from Example 8 (comprising SDS) demonstrated long-term chemical stability and antimicrobial efficacy of using SDS as an additive partner for 3 -silver- 1-methylimidazole.
[0053] Comparing FIG. 6 to FIGS. 3, 4 and 5 shows the effectiveness of the
antimicrobial composition. Only plates 2, 3, and 5 showed any reduction of the microorganisms with the control 1% SDS solution (FIG. 6), whereas all plates in FIGS. 3, 4 and 5 showed effective reduction in the microorganisms. Thus, the performance of dispersible antimicrobial composition from Example 8 (comprising SDS) showed greater broad-spectrum effectiveness than the 1% SDS solution alone. Furthermore, the dispersible antimicrobial composition from Example 8 (comprising SDS) still showed strong antimicrobial effectiveness after 180 days of shelf-life (FIG. 5).
Example 10: Comparison to conventional disinfectants
[0054] An efficacy assay was conducted to test the bactericidal/fungicidal activity of the dispersible antimicrobial composition from Example 8 (comprising SDS) compared to conventional disinfectants, sodium hypochlorite (10% bleach solution) and ethanol (70% solution). The assay consisted of inoculating a lawn of bacteria/yeast from a newly grown broth culture onto their preferred agar media by dipping a cotton swap into each broth, fully wetting the swab end, then swiping the swab back-and-forth from the top to the bottom of the plate, then turning the plate for a ¼ turn and re-streaking from top to bottom again. This technique ensured total coverage of the inoculating bacteria/yeast across the face of the agar media. The dish was then opened and a paper towel placed over the top of the plate to cover only half of the surface while not touching the agar surface, leaving the other half exposed. This exposed half (the left side of the plate in the figures included herein) was then treated with 2-pumps from a spray bottle containing the treatment solution, ensuring that the exposed half of the plate was saturated with the antimicrobial composition. Each plate was treated using the same 2-pump criteria. All plates were then incubated "agar-down" overnight to allow the bacteria/yeast to fully grow. The bacterial plates were maintained at 37 °C; the yeast plates were maintained at 30 °C. For this test, a positive result was the treated half was clear of bacteria growth. The control side may show full grown lawn of bacteria or reduced lawn growth depending on efficacy of the agent tested. The results of the efficacy assay are provided in FIG. 7. The microorganisms tested are shown in the table below:
Figure imgf000016_0001
[0055] The dispersible antimicrobial composition showed a high level of effectiveness on the treated side (left side) of all the plates (FIG. 7). The antimicrobial composition showed such a high level of effectiveness that it was difficult to find bacterial growth on the untreated side of test plate 3.
[0056] Comparing the silver-based antimicrobial composition comprising 3-silver-l- methylimidazole to the sodium hypochlorite solution, the composition showed substantially equivalent effectiveness on the treated side of the plates, but exhibited greater migration into the untreated side of the plate than the sodium hypochlorite solution. Comparing the composition to the ethanol, the ethanol exhibited virtually no kill of the microbes on plates 2 and 5, minimal kill in plate 3 as shown by the disruption of the bacterial lawn in the lower left corner, and moderate effectiveness in plates 1 and 4. Thus, the silver-based antimicrobial composition showed superior antimicrobial effectiveness as compared to conventional disinfectant agents, sodium hypochlorite and ethanol. A control of 1% SDS exhibited virtually no kill on treated plates 2 and 4, moderate effectiveness in plate 1, and substantial kill effectiveness in plates 3 and 5. Thus, the efficacy demonstrated with the antimicrobial composition 3 -silver- 1-methylimidazole was superior to the 1% SDS solution alone. Illustrative embodiments of suitable methods, products, and systems.
[0057] As used below, any reference to methods, compositions, or articles is understood as a reference to each of those methods, compositions, or articles disjunctively (e.g., "Illustrative embodiment 1-4 is understood as illustrative embodiment 1, 2, 3, or 4.").
[0058] Illustrative embodiment 1 is an antimicrobial composition comprising about:
0.5 to 10 wt.% silver particles; 40 to 60 wt.% 1-methylimidazole; 10 to 25 wt.% lactic acid; and deionized water.
[0059] Illustrative embodiment 2 is the composition of any preceding or subsequent illustrative embodiment, further comprising about 0.3 wt.% sodium dodecyl sulfate.
[0060] Illustrative embodiment 3 is a silver-based antimicrobial gel composition comprising about: 0.05 to 5 wt.% of the composition of any of any preceding or subsequent illustrative embodiment; and a chitosan gel, wherein the chitosan gel comprises about 0.1 to 5 wt.%) chitosan powder, 1 to 15 wt.%> glycerol, 0.1 to 5 wt.%> lactic acid, and deionized water.
[0061] Illustrative embodiment 4 is the composition of any preceding or subsequent illustrative embodiment, further comprising about 0.5 to 2 wt.%> dimethyl sulfoxide.
[0062] Illustrative embodiment 5 is an antimicrobial solution comprising about: 0.001 to
10 vol.%) of the composition of of any preceding or subsequent illustrative embodiment; and a sodium tetraborate decahydrate solution, wherein the sodium tetraborate decahydrate solution comprises about 0.5 to 4 wt.%> sodium tetraborate decahydrate and deionized water.
[0063] Illustrative embodiment 6 is an antimicrobial solution comprising about: 0.001 to
10 vol.%) of the composition of any of any preceding or subsequent illustrative embodiment; and a sodium dodecyl sulfate solution, wherein the sodium dodecyl sulfate solution comprises about 0.5 to 4 wt.%) sodium dodecyl sulfate and deionized water.
[0064] Illustrative embodiment 7 is the composition of any preceding or subsequent illustrative embodiment, wherein the composition is capable of forming a mist.
[0065] Illustrative embodiment 8 is the composition of any preceding or subsequent illustrative embodiment, wherein the composition has a pH between 8 and 10.
[0066] Illustrative embodiment 9 is a method of making an antimicrobial composition comprising: adding deionized water to a silver powder in a vessel; mixing the composition until the silver is essentially wetted; adding 1-methylimidazole to the vessel; adding lactic acid to the vessel; and mixing the vessel until the composition is an essentially homogeneous solution with substantially no clumps.
[0067] Illustrative embodiment 10 is the method of any preceding or subsequent illustrative embodiment, further comprising: preparing a solution of sodium dodecyl sulfate and deionized water in a first vessel; and adding the sodium dodecyl sulfate solution to the silver powder of any preceding or subsequent illustrative embodiment.
[0068] Illustrative embodiment 11 is a method of making a silver-based antimicrobial gel comprising: combining chitosan powder, glycerol, and deionized water in a vessel; essentially dispersing the chitosan by mixing; adding lactic acid to the vessel; essentially dissolving the chitosan; and adding the composition from any preceding or subsequent illustrative embodiment to the vessel.
[0069] Illustrative embodiment 12 is the method of any preceding or subsequent illustrative embodiment, further comprising adding dimethyl sulfoxide to the vessel.
[0070] Illustrative embodiment 13 is a method of making a silver-based antimicrobial solution comprising: heating deionized water in a vessel; adding sodium tetraborate decahydrate to the deionized water; essentially dissolving the sodium tetraborate decahydrate; adding the composition from any preceding or subsequent illustrative embodiment to the vessel; and mixing the vessel until the solution is essentially homogeneous.
[0071] Illustrative embodiment 14 is the method of any preceding or subsequent illustrative embodiment, wherein the deionized water is heated to between 30°C and 50°C.
[0072] Illustrative embodiment 15 is a method of making a silver-based antimicrobial solution comprising: combining deionized water and sodium dodecyl sulfate in a vessel;
essentially dissolving the sodium dodecyl sulfate; adding the composition from any preceding or subsequent illustrative embodiment to the vessel; and mixing the vessel until the solution is essentially homogeneous.
[0073] Illustrative embodiment 16 is the method of any preceding or subsequent illustrative embodiment, wherein mixing comprises agitating, sonicating, vortexing, stirring, shaking, and circulating.
[0074] Illustrative embodiment 17 is an article of manufacture comprising the composition of any preceding or subsequent illustrative embodiment. [0075] Illustrative embodiment 18 is the article of manufacture of any preceding or subsequent illustrative embodiment, wherein the composition is capable of being dispersed as a mist.
[0076] Illustrative embodiment 19 is a method for using the composition of any preceding or subsequent illustrative embodiment to minimize microorganisms comprising introducing the composition to an environment.
[0077] Illustrative embodiment 20 is the method of any preceding or subsequent illustrative embodiment, wherein the composition is applied to a surface, wherein said surface comprises a living being or article of manufacture.
[0078] Illustrative embodiment 21 is the method of any preceding or subsequent illustrative embodiment, wherein the living being comprises a portion of a human or an animal.
[0079] Illustrative embodiment 22 is the method of any preceding or subsequent illustrative embodiment, wherein article of manufacture comprises counter-tops, sinks, door knobs, walls, floor coverings, bathroom fixtures, furniture, and upholstery.
[0080] Illustrative embodiment 23 is the method of any preceding or subsequent illustrative embodiment, wherein the composition is introduced in forms comprising at least one of a liquid, an aerosol, a gel, or a powder.
[0081] The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to") unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individual recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated or clearly contradicted by context.
[0082] Various embodiments of the invention have been described herein. It should be recognized that these embodiments are merely illustrative of the present invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated or otherwise clearly contradicted by context.

Claims

WHAT IS CLAIMED IS:
1. An antimicrobial composition comprising about:
0.5 to 10 wt.% silver particles;
40 to 60 wt.% 1-methylimidazole;
10 to 25 wt.%) lactic acid; and
deionized water.
2. The composition of claim 1, further comprising about 0.3 wt.%> sodium dodecyl sulfate.
3. A silver-based antimicrobial gel composition comprising about:
0.05 to 5 wt.%) of the composition of any one of claims 1-2; and
a chitosan gel, wherein the chitosan gel comprises about
0.1 to 5 wt.%) chitosan powder,
1 to 15 wt.%) glycerol,
0.1 to 5 wt.%) lactic acid, and
deionized water.
4. The silver-based antimicrobial gel composition of claim 3, further comprising about 0.5 to 2 wt.%) dimethyl sulfoxide.
5. An antimicrobial solution comprising about:
0.001 to 10 vol.%0 of the composition of any one of claims 1-2; and
a sodium tetraborate decahydrate solution, wherein the sodium tetraborate decahydrate solution comprises about 0.5 to 4 wt.%> sodium tetraborate decahydrate and deionized water.
6. An antimicrobial solution comprising about:
0.001 to 10 vol.%0 of the composition of any one of claims 1-2; and
a sodium dodecyl sulfate solution, wherein the sodium dodecyl sulfate solution comprises about 0.5 to 4 wt.%> sodium dodecyl sulfate and deionized water.
7. The composition of any one of claims 1-6, wherein the composition has a pH between 8 and 10.
8. A method of making an antimicrobial composition comprising:
adding deionized water to a silver powder in a vessel;
mixing the composition until the silver is essentially wetted;
adding 1-methylimidazole to the vessel;
adding lactic acid to the vessel; and
mixing the vessel until the composition is an essentially homogeneous solution with substantially no clumps.
9. The method of claim 8, further comprising:
preparing a solution of sodium dodecyl sulfate and deionized water in a first vessel; and adding the sodium dodecyl sulfate solution to the silver powder.
10. A method of making a silver-based antimicrobial gel comprising:
combining chitosan powder, glycerol, and deionized water in a vessel;
essentially dispersing the chitosan by mixing;
adding lactic acid to the vessel;
essentially dissolving the chitosan; and
adding the composition from any one of claims 1-2 to the vessel.
11. The method of claim 10, further comprising adding dimethyl sulfoxide to the vessel.
12. A method of making a silver-based antimicrobial solution comprising:
heating deionized water in a vessel;
adding sodium tetraborate decahydrate to the deionized water;
essentially dissolving the sodium tetraborate decahydrate;
adding the composition from any one of claims 1-2 to the vessel; and mixing the vessel until the solution is essentially homogeneous.
13. The method of claim 12, wherein the deionized water is heated to between 30°C and 50°C.
14. A method of making a silver-based antimicrobial solution comprising:
combining deionized water and sodium dodecyl sulfate in a vessel;
essentially dissolving the sodium dodecyl sulfate;
adding the composition from any one of claims 1-2 to the vessel; and
mixing the vessel until the solution is essentially homogeneous.
15. The methods of any one of claims 8-14, wherein mixing comprises agitating, sonicating, vortexing, stirring, shaking, and circulating.
16. An article of manufacture comprising the composition of any one of claims 1-7.
17. The article of manufacture of claim 16, wherein the composition is capable of being dispersed as a mist.
18. A method for using the composition of any one of claims 1-7 to minimize
microorganisms comprising introducing the composition to an environment.
19. The method of claim 18, wherein the composition is applied to a surface, wherein said surface comprises a living being or article of manufacture.
20. The method of claim 18, wherein the composition is introduced in forms comprising a liquid, an aerosol, a gel, and/or a powder.
PCT/US2018/033905 2017-05-23 2018-05-22 Antimicrobial composition Ceased WO2018217761A1 (en)

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