WO2013158165A1 - Long-lasting surface anti-microbial and method of application - Google Patents
Long-lasting surface anti-microbial and method of application Download PDFInfo
- Publication number
- WO2013158165A1 WO2013158165A1 PCT/US2013/020254 US2013020254W WO2013158165A1 WO 2013158165 A1 WO2013158165 A1 WO 2013158165A1 US 2013020254 W US2013020254 W US 2013020254W WO 2013158165 A1 WO2013158165 A1 WO 2013158165A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- barrier
- composition
- forming composition
- microorganisms
- antimicrobial
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 81
- 230000000845 anti-microbial effect Effects 0.000 title claims abstract description 71
- 239000004599 antimicrobial Substances 0.000 title claims abstract description 57
- 230000005923 long-lasting effect Effects 0.000 title abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 473
- 230000004888 barrier function Effects 0.000 claims abstract description 155
- 244000005700 microbiome Species 0.000 claims abstract description 141
- 230000012010 growth Effects 0.000 claims abstract description 54
- 230000000813 microbial effect Effects 0.000 claims abstract description 52
- 230000002147 killing effect Effects 0.000 claims abstract description 30
- 230000000007 visual effect Effects 0.000 claims abstract description 18
- 230000003068 static effect Effects 0.000 claims abstract description 13
- 238000002845 discoloration Methods 0.000 claims abstract description 11
- 230000005532 trapping Effects 0.000 claims abstract description 9
- 230000003472 neutralizing effect Effects 0.000 claims abstract description 8
- 239000003906 humectant Substances 0.000 claims description 30
- 235000013305 food Nutrition 0.000 claims description 26
- 230000003612 virological effect Effects 0.000 claims description 24
- 241000222122 Candida albicans Species 0.000 claims description 23
- 241000194019 Streptococcus mutans Species 0.000 claims description 22
- 241000712461 unidentified influenza virus Species 0.000 claims description 17
- 150000001720 carbohydrates Chemical class 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 230000009931 harmful effect Effects 0.000 claims description 15
- 241000709661 Enterovirus Species 0.000 claims description 14
- 230000002538 fungal effect Effects 0.000 claims description 14
- -1 linoleum Substances 0.000 claims description 14
- 230000001580 bacterial effect Effects 0.000 claims description 13
- 230000003247 decreasing effect Effects 0.000 claims description 11
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 9
- 241001134658 Streptococcus mitis Species 0.000 claims description 9
- 241000194025 Streptococcus oralis Species 0.000 claims description 9
- 241000194024 Streptococcus salivarius Species 0.000 claims description 9
- 238000011109 contamination Methods 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 8
- 206010041925 Staphylococcal infections Diseases 0.000 claims description 8
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 231100000252 nontoxic Toxicity 0.000 claims description 8
- 230000003000 nontoxic effect Effects 0.000 claims description 8
- 238000005507 spraying Methods 0.000 claims description 8
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 claims description 7
- 241000194023 Streptococcus sanguinis Species 0.000 claims description 7
- 229960001927 cetylpyridinium chloride Drugs 0.000 claims description 7
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 7
- 230000004044 response Effects 0.000 claims description 7
- 241000606125 Bacteroides Species 0.000 claims description 6
- 229910052709 silver Inorganic materials 0.000 claims description 6
- 239000004332 silver Substances 0.000 claims description 6
- 239000002023 wood Substances 0.000 claims description 6
- 241000606749 Aggregatibacter actinomycetemcomitans Species 0.000 claims description 5
- 241000605862 Porphyromonas gingivalis Species 0.000 claims description 5
- 241000194017 Streptococcus Species 0.000 claims description 5
- 241000194026 Streptococcus gordonii Species 0.000 claims description 5
- 125000002091 cationic group Chemical group 0.000 claims description 5
- 229960003260 chlorhexidine Drugs 0.000 claims description 5
- 241001225321 Aspergillus fumigatus Species 0.000 claims description 4
- 229940123208 Biguanide Drugs 0.000 claims description 4
- 241000588832 Bordetella pertussis Species 0.000 claims description 4
- 244000197813 Camelina sativa Species 0.000 claims description 4
- 241000222178 Candida tropicalis Species 0.000 claims description 4
- 241000605986 Fusobacterium nucleatum Species 0.000 claims description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 241000235645 Pichia kudriavzevii Species 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 241001135235 Tannerella forsythia Species 0.000 claims description 4
- 241000607447 Yersinia enterocolitica Species 0.000 claims description 4
- 150000003868 ammonium compounds Chemical group 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 229940091771 aspergillus fumigatus Drugs 0.000 claims description 4
- 150000004283 biguanides Chemical class 0.000 claims description 4
- 239000000919 ceramic Substances 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000004575 stone Substances 0.000 claims description 4
- 241000589291 Acinetobacter Species 0.000 claims description 3
- 241000222290 Cladosporium Species 0.000 claims description 3
- 229920000742 Cotton Polymers 0.000 claims description 3
- 241000588724 Escherichia coli Species 0.000 claims description 3
- 241000282412 Homo Species 0.000 claims description 3
- 229920000297 Rayon Polymers 0.000 claims description 3
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 3
- 241000700584 Simplexvirus Species 0.000 claims description 3
- 241000193998 Streptococcus pneumoniae Species 0.000 claims description 3
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 3
- 239000003082 abrasive agent Substances 0.000 claims description 3
- 239000004033 plastic Substances 0.000 claims description 3
- 229920003023 plastic Polymers 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 208000020029 respiratory tract infectious disease Diseases 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000004381 surface treatment Methods 0.000 claims description 3
- 239000012855 volatile organic compound Substances 0.000 claims description 3
- VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Chemical compound CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 claims description 2
- VPWNQTHUCYMVMZ-UHFFFAOYSA-N 4,4'-sulfonyldiphenol Chemical class C1=CC(O)=CC=C1S(=O)(=O)C1=CC=C(O)C=C1 VPWNQTHUCYMVMZ-UHFFFAOYSA-N 0.000 claims description 2
- 244000198134 Agave sisalana Species 0.000 claims description 2
- 229930185605 Bisphenol Natural products 0.000 claims description 2
- 229910001369 Brass Inorganic materials 0.000 claims description 2
- 229910000906 Bronze Inorganic materials 0.000 claims description 2
- 241001453380 Burkholderia Species 0.000 claims description 2
- 244000025254 Cannabis sativa Species 0.000 claims description 2
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 claims description 2
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 claims description 2
- 229920000049 Carbon (fiber) Polymers 0.000 claims description 2
- 241001633684 Centipeda periodontii Species 0.000 claims description 2
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 2
- 241000193163 Clostridioides difficile Species 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- 241000588878 Eikenella corrodens Species 0.000 claims description 2
- 241000588921 Enterobacteriaceae Species 0.000 claims description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 2
- 241001251094 Formica Species 0.000 claims description 2
- 241001291923 Fusobacterium nucleatum subsp. nucleatum Species 0.000 claims description 2
- 241001291922 Fusobacterium nucleatum subsp. polymorphum Species 0.000 claims description 2
- 241000009790 Fusobacterium nucleatum subsp. vincentii Species 0.000 claims description 2
- 241000219146 Gossypium Species 0.000 claims description 2
- 241000709721 Hepatovirus A Species 0.000 claims description 2
- 241000709701 Human poliovirus 1 Species 0.000 claims description 2
- 241000712431 Influenza A virus Species 0.000 claims description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 claims description 2
- 235000019738 Limestone Nutrition 0.000 claims description 2
- 239000004677 Nylon Substances 0.000 claims description 2
- 241000228143 Penicillium Species 0.000 claims description 2
- 229920002413 Polyhexanide Polymers 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 241001135213 Porphyromonas endodontalis Species 0.000 claims description 2
- 241000605861 Prevotella Species 0.000 claims description 2
- 241001135221 Prevotella intermedia Species 0.000 claims description 2
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 2
- 241000702670 Rotavirus Species 0.000 claims description 2
- 241001138501 Salmonella enterica Species 0.000 claims description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- 241001464874 Solobacterium moorei Species 0.000 claims description 2
- 229920002334 Spandex Polymers 0.000 claims description 2
- 229910000831 Steel Inorganic materials 0.000 claims description 2
- 241000589892 Treponema denticola Species 0.000 claims description 2
- 241001045770 Trichophyton mentagrophytes Species 0.000 claims description 2
- 229910000754 Wrought iron Inorganic materials 0.000 claims description 2
- OAAKZKGKPMPJIF-UHFFFAOYSA-N [Cl].[I] Chemical compound [Cl].[I] OAAKZKGKPMPJIF-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims description 2
- 229910045601 alloy Inorganic materials 0.000 claims description 2
- 239000000956 alloy Substances 0.000 claims description 2
- RREGISFBPQOLTM-UHFFFAOYSA-N alumane;trihydrate Chemical compound O.O.O.[AlH3] RREGISFBPQOLTM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 239000004760 aramid Substances 0.000 claims description 2
- 229920003235 aromatic polyamide Polymers 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- OCBHHZMJRVXXQK-UHFFFAOYSA-M benzyl-dimethyl-tetradecylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 OCBHHZMJRVXXQK-UHFFFAOYSA-M 0.000 claims description 2
- 150000004287 bisbiguanides Chemical class 0.000 claims description 2
- 239000010951 brass Substances 0.000 claims description 2
- 239000010974 bronze Substances 0.000 claims description 2
- 235000009120 camo Nutrition 0.000 claims description 2
- 239000004917 carbon fiber Substances 0.000 claims description 2
- SXPWTBGAZSPLHA-UHFFFAOYSA-M cetalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SXPWTBGAZSPLHA-UHFFFAOYSA-M 0.000 claims description 2
- 229960000228 cetalkonium chloride Drugs 0.000 claims description 2
- 229960002798 cetrimide Drugs 0.000 claims description 2
- 235000005607 chanvre indien Nutrition 0.000 claims description 2
- 239000004567 concrete Substances 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- KUNSUQLRTQLHQQ-UHFFFAOYSA-N copper tin Chemical compound [Cu].[Sn] KUNSUQLRTQLHQQ-UHFFFAOYSA-N 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 229920001971 elastomer Polymers 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 238000009408 flooring Methods 0.000 claims description 2
- 239000004088 foaming agent Substances 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052737 gold Inorganic materials 0.000 claims description 2
- 239000010931 gold Substances 0.000 claims description 2
- 239000010438 granite Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000011487 hemp Substances 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 239000006028 limestone Substances 0.000 claims description 2
- 239000004579 marble Substances 0.000 claims description 2
- 150000002739 metals Chemical class 0.000 claims description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 2
- 229940094510 myristalkonium chloride Drugs 0.000 claims description 2
- 229920001778 nylon Polymers 0.000 claims description 2
- 150000002989 phenols Chemical class 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 229920000058 polyacrylate Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 239000010453 quartz Substances 0.000 claims description 2
- 239000002964 rayon Substances 0.000 claims description 2
- 239000005060 rubber Substances 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960003600 silver sulfadiazine Drugs 0.000 claims description 2
- UEJSSZHHYBHCEL-UHFFFAOYSA-N silver(1+) sulfadiazinate Chemical compound [Ag+].C1=CC(N)=CC=C1S(=O)(=O)[N-]C1=NC=CC=N1 UEJSSZHHYBHCEL-UHFFFAOYSA-N 0.000 claims description 2
- 239000010454 slate Substances 0.000 claims description 2
- 239000004759 spandex Substances 0.000 claims description 2
- 239000010935 stainless steel Substances 0.000 claims description 2
- 229910001220 stainless steel Inorganic materials 0.000 claims description 2
- 239000010959 steel Substances 0.000 claims description 2
- 150000005846 sugar alcohols Polymers 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000004753 textile Substances 0.000 claims description 2
- 239000010409 thin film Substances 0.000 claims description 2
- 210000002268 wool Anatomy 0.000 claims description 2
- 241000605994 Fusobacterium periodonticum Species 0.000 claims 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 61
- 230000002401 inhibitory effect Effects 0.000 abstract description 11
- 230000009977 dual effect Effects 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 104
- 238000011282 treatment Methods 0.000 description 48
- 208000015181 infectious disease Diseases 0.000 description 46
- 238000009472 formulation Methods 0.000 description 33
- 239000010410 layer Substances 0.000 description 32
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 31
- 210000001519 tissue Anatomy 0.000 description 28
- 241000700605 Viruses Species 0.000 description 27
- 241000894006 Bacteria Species 0.000 description 25
- 230000002265 prevention Effects 0.000 description 25
- 238000010790 dilution Methods 0.000 description 24
- 239000012895 dilution Substances 0.000 description 24
- 210000004877 mucosa Anatomy 0.000 description 24
- 210000002919 epithelial cell Anatomy 0.000 description 23
- 229920001285 xanthan gum Polymers 0.000 description 23
- 239000000230 xanthan gum Substances 0.000 description 23
- 229940082509 xanthan gum Drugs 0.000 description 23
- 241000233866 Fungi Species 0.000 description 22
- 238000012360 testing method Methods 0.000 description 22
- 229920001817 Agar Polymers 0.000 description 21
- 239000008272 agar Substances 0.000 description 21
- 235000019645 odor Nutrition 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 235000010493 xanthan gum Nutrition 0.000 description 20
- 210000000214 mouth Anatomy 0.000 description 18
- 239000007921 spray Substances 0.000 description 18
- 208000027418 Wounds and injury Diseases 0.000 description 17
- 210000002950 fibroblast Anatomy 0.000 description 17
- 230000006378 damage Effects 0.000 description 16
- 241000124008 Mammalia Species 0.000 description 15
- 206010052428 Wound Diseases 0.000 description 15
- 235000011187 glycerol Nutrition 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 15
- 239000002609 medium Substances 0.000 description 15
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 14
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 14
- 239000011248 coating agent Substances 0.000 description 14
- 238000000576 coating method Methods 0.000 description 14
- 210000004400 mucous membrane Anatomy 0.000 description 14
- 238000003556 assay Methods 0.000 description 13
- 239000001963 growth medium Substances 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- 238000004113 cell culture Methods 0.000 description 12
- 206010022000 influenza Diseases 0.000 description 12
- 208000035473 Communicable disease Diseases 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 241000725303 Human immunodeficiency virus Species 0.000 description 10
- 239000013553 cell monolayer Substances 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 10
- 230000000120 cytopathologic effect Effects 0.000 description 10
- 210000002200 mouth mucosa Anatomy 0.000 description 10
- 239000003755 preservative agent Substances 0.000 description 10
- 230000000840 anti-viral effect Effects 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 238000003753 real-time PCR Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000012292 cell migration Effects 0.000 description 8
- 239000012228 culture supernatant Substances 0.000 description 8
- 238000013508 migration Methods 0.000 description 8
- 230000037314 wound repair Effects 0.000 description 8
- 230000010261 cell growth Effects 0.000 description 7
- 230000002209 hydrophobic effect Effects 0.000 description 7
- 238000010166 immunofluorescence Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000002203 pretreatment Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 238000002784 cytotoxicity assay Methods 0.000 description 6
- 231100000263 cytotoxicity test Toxicity 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000009545 invasion Effects 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 230000000451 tissue damage Effects 0.000 description 6
- 231100000827 tissue damage Toxicity 0.000 description 6
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 5
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 5
- 208000036142 Viral infection Diseases 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 244000052616 bacterial pathogen Species 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229940043350 citral Drugs 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 210000000981 epithelium Anatomy 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002356 single layer Substances 0.000 description 5
- 230000009385 viral infection Effects 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 206010061598 Immunodeficiency Diseases 0.000 description 4
- 102100034343 Integrase Human genes 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- OSVXSBDYLRYLIG-UHFFFAOYSA-N dioxidochlorine(.) Chemical compound O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000010408 film Substances 0.000 description 4
- 210000001648 gingival epithelial cell Anatomy 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 4
- 230000000149 penetrating effect Effects 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 239000012449 sabouraud dextrose agar Substances 0.000 description 4
- 229920002379 silicone rubber Polymers 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000002459 sustained effect Effects 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- OSDLLIBGSJNGJE-UHFFFAOYSA-N 4-chloro-3,5-dimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1Cl OSDLLIBGSJNGJE-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 240000008415 Lactuca sativa Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000012124 Opti-MEM Substances 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241001148470 aerobic bacillus Species 0.000 description 3
- 239000013566 allergen Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000032770 biofilm formation Effects 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 229940095731 candida albicans Drugs 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 230000001332 colony forming effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 239000004017 serum-free culture medium Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 239000000606 toothpaste Substances 0.000 description 3
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- WEEGYLXZBRQIMU-UHFFFAOYSA-N 1,8-cineole Natural products C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 2
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 241000588626 Acinetobacter baumannii Species 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 206010006326 Breath odour Diseases 0.000 description 2
- 239000004155 Chlorine dioxide Substances 0.000 description 2
- 241000282552 Chlorocebus aethiops Species 0.000 description 2
- 244000000626 Daucus carota Species 0.000 description 2
- 235000002767 Daucus carota Nutrition 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 2
- 241000701806 Human papillomavirus Species 0.000 description 2
- 101100508198 Leptospira borgpetersenii serovar Hardjo-bovis (strain L550) infA2 gene Proteins 0.000 description 2
- 229920000161 Locust bean gum Polymers 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 239000006159 Sabouraud's agar Substances 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 206010048908 Seasonal allergy Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 241001279361 Stachybotrys Species 0.000 description 2
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 2
- 108020000999 Viral RNA Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000036436 anti-hiv Effects 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 235000019398 chlorine dioxide Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229960005233 cineole Drugs 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 208000002925 dental caries Diseases 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 229960001484 edetic acid Drugs 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 208000007565 gingivitis Diseases 0.000 description 2
- 239000011440 grout Substances 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 238000010820 immunofluorescence microscopy Methods 0.000 description 2
- 101150071451 infA gene Proteins 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 208000037797 influenza A Diseases 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000002085 irritant Substances 0.000 description 2
- 231100000021 irritant Toxicity 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 235000010420 locust bean gum Nutrition 0.000 description 2
- 239000000711 locust bean gum Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 235000019799 monosodium phosphate Nutrition 0.000 description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 2
- 239000012120 mounting media Substances 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 229940051866 mouthwash Drugs 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 235000012045 salad Nutrition 0.000 description 2
- 238000011012 sanitization Methods 0.000 description 2
- 238000004626 scanning electron microscopy Methods 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- 238000002287 time-lapse microscopy Methods 0.000 description 2
- 229940034610 toothpaste Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- WZRJTRPJURQBRM-UHFFFAOYSA-N 4-amino-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1.COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 WZRJTRPJURQBRM-UHFFFAOYSA-N 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 description 1
- 208000003508 Botulism Diseases 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000004221 Brassica oleracea var gemmifera Nutrition 0.000 description 1
- 235000017647 Brassica oleracea var italica Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- 244000308368 Brassica oleracea var. gemmifera Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- PGLIUCLTXOYQMV-UHFFFAOYSA-N Cetirizine hydrochloride Chemical class Cl.Cl.C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 PGLIUCLTXOYQMV-UHFFFAOYSA-N 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 101710088719 Ead protein Proteins 0.000 description 1
- 108010049047 Echinocandins Proteins 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- IECPWNUMDGFDKC-UHFFFAOYSA-N Fusicsaeure Natural products C12C(O)CC3C(=C(CCC=C(C)C)C(O)=O)C(OC(C)=O)CC3(C)C1(C)CCC1C2(C)CCC(O)C1C IECPWNUMDGFDKC-UHFFFAOYSA-N 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000569 Gum karaya Polymers 0.000 description 1
- 208000032139 Halitosis Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 1
- 231100000416 LDH assay Toxicity 0.000 description 1
- 235000003228 Lactuca sativa Nutrition 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 244000070406 Malus silvestris Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 206010048685 Oral infection Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- 229920001131 Pulp (paper) Polymers 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 241001237745 Salamis Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 208000019802 Sexually transmitted disease Diseases 0.000 description 1
- 238000011869 Shapiro-Wilk test Methods 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 235000009337 Spinacia oleracea Nutrition 0.000 description 1
- 244000300264 Spinacia oleracea Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000009635 antibiotic susceptibility testing Methods 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229960004574 azelastine Drugs 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 235000021015 bananas Nutrition 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013098 chemical test method Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 1
- 229960005443 chloroxylenol Drugs 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229920001531 copovidone Polymers 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- ZXJXZNDDNMQXFV-UHFFFAOYSA-M crystal violet Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1[C+](C=1C=CC(=CC=1)N(C)C)C1=CC=C(N(C)C)C=C1 ZXJXZNDDNMQXFV-UHFFFAOYSA-M 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 239000003975 dentin desensitizing agent Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 235000015244 frankfurter Nutrition 0.000 description 1
- 239000012737 fresh medium Chemical group 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 229960004675 fusidic acid Drugs 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 229960001235 gentian violet Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 230000001632 homeopathic effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 235000010494 karaya gum Nutrition 0.000 description 1
- 238000002843 lactate dehydrogenase assay Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 239000013586 microbial product Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229940095518 mouthwash product Drugs 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 244000309462 non-albicans Candida Species 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 235000014571 nuts Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052573 porcelain Inorganic materials 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000020991 processed meat Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 235000020995 raw meat Nutrition 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 235000015175 salami Nutrition 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 235000020354 squash Nutrition 0.000 description 1
- 210000005127 stratified epithelium Anatomy 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 238000010610 time kill assay Methods 0.000 description 1
- 201000004647 tinea pedis Diseases 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 239000007852 tooth bleaching agent Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/23—Solid substances, e.g. granules, powders, blocks, tablets
- A61L2/232—Solid substances, e.g. granules, powders, blocks, tablets layered or coated
Definitions
- This disclosure relates to barrier-forming compositions and methods for treating surfaces to prevent the spread of communicable diseases.
- compositions have been developed for killing germs on household surfaces, healthcare facility surfaces, workplace or office surfaces, and other various surfaces that from time to time become contaminated.
- these compositions typically contain highly volatile organic compounds, and although they almost immediately kill microorganisms, they quickly evaporate and/or are washed or wiped away and do not continue to inhibit microorganism growth for more than a few minutes.
- it is unlikely that a quick application of such compositions will kill all the microorganisms present on the surface. Thus, the remaining microorganisms will inevitably begin regrowing in a short time.
- compositions have also been developed that mask or destroy odors or act to kill mold or other microorganisms that cause a deterioration in a visual aspect of a surface.
- improvements in a long-lasting, powerful and generally non-toxic solution for such uses is desirable.
- a method for trapping and neutralizing or killing microorganisms on a surface includes: applying a barrier-forming composition that comprises an
- the antimicrobial agent onto an inanimate surface; forming a barrier layer on the inanimate surface; in the barrier, trapping and killing microorganisms encountered on the surface and encountered from the environment after the applying step is performed.
- the barrier layer has an antimicrobial cidal or static activity for a duration of at least about one hour.
- a barrier-forming composition for a surface treatment includes: a carbohydrate gum, a humectant, and an antimicrobial agent.
- the barrier-forming composition meets the following requirements:
- C is the carbohydrate gum
- H is the humectant
- A is the antimicrobial agent.
- the barrier composition is active to trap, and neutralize or kill microorganisms.
- a pre-treated, disposable wipe includes a disposable wipe material at least partially saturated with a composition.
- the composition includes a carbohydrate gum, a humectant, and an antibacterial agent.
- the barrier-forming composition meets the following requirements:
- C is the carbohydrate gum
- H is the humectant
- A is the antimicrobial agent
- a method includes: preventing or decreasing odor produced by microorganisms, by applying a barrier-forming composition that comprises an antimicrobial onto an inanimate surface; forming a barrier layer on the inanimate surface that is active to trap and kill or neutralize microorganisms encountered by the barrier layer for a duration of at least about one hour, thereby preventing or decreasing odor generated by microorganisms from escaping the barrier layer.
- a method includes preventing or treating a detraction of a visual appearance of a surface, the detraction being caused by microorganisms that produce a visible growth on the surface or discoloration of the surface, by: applying a barrier-forming composition that comprises an antimicrobial onto the surface; forming a barrier layer on the surface that is active to trap, and kill or neutralize microorganisms encountered by the barrier layer for a duration of at least about one hour thereby preventing or decreasing the visible growth or discoloration on the surface.
- a method for trapping, and neutralizing or killing microorganisms that cause infectious disease includes: applying a barrier-forming composition that comprises an antimicrobial onto a surface of an apparatus; forming a barrier coating on the surface of the apparatus that is active to trap and kill or neutralize microorganisms encountered by the barrier layer for a duration of at least about one hour thereby preventing or decreasing the risk of infection from the microorganisms.
- mammal means a human or animal commonly defined as a mammal.
- blocking includes blocking passage by trapping.
- Figure 1A is an illustrated flow chart of a treated and untreated inanimate surface and the results of an encounter with microorganisms.
- Figure IB is a depiction of a proposed mechanism of antimicrobial activity in an embodiment of the barrier-forming composition.
- Figure 2 is a schematic showing the formation of a barrier on a mucosal surface, as described in Example 2.
- Figure 3 is a graph showing the repair process as a percentage on a wounded epithelial cell sample through cell growth and migration after 6 hours to cover the scratched space in each of Examples 1 1-15.
- Figure 4 shows microscopic photographs showing epithelial cell growth and migration on both untreated control Example 15 and treated Examples 16 and 17 on a wounded epithelial sample.
- Figure 5 shows photos of magnified cross-sections of the barrier-forming
- composition-treated and untreated engineered human oral mucosa of Examples 1 1- 15.
- Figure 6 is graph showing an LDH assay of Examples 16-19 and 20-25.
- Figure 7 is a schema showing the method of evaluation of microbial growth in the upper and lower chambers of an EHOM assay, as described in Examples 27-28.
- Figure 8 show photographs of agar media plates showing microbial growth in the upper and lower chambers of an EHOM assay, as described in Examples 27-28.
- FIG. 9 shows photographs of magnified cross-sections of the barrier-forming composition-treated and untreated engineered human oral mucosa (EHOM) of Examples 31-
- Figure 10 shows photographs of microbial growth on untreated EHOM or EHOM treated with an example barrier-forming composition, followed by infection with C. albicans, as described in Examples 33-40.
- Figure 11 shows photographs of microbial growth on untreated EHOM or EHOM treated with formulations followed by infection with S. mutans, as described in Examples 33- 40.
- Figure 12 shows photographs of microbial growth from "flow-through" media (collected from the lower chamber) of EHOM treated with an example barrier-forming composition, as described in Example 33-40.
- Figure 13 presents graphs showing LDH release by EHOM treated with saline (control) or example barrier-forming compositions, followed by infection with (A) C.
- Figure 14 is a graph showing post-antimicrobial effect of barrier- forming
- compositions against bacteria and fungi as described in Examples 48-61 and 61-69.
- Figure 15 shows scanning electron micrographs of S. sanguis, C. albicans, and S. mutans, untreated or treated with barrier-forming composition, as described in Examples 71- 76.
- Figure 16 presents graphs depicting activity of an example barrier-forming composition against biofilms formed by bacteria and fungi, as described in Examples 77-79.
- Figure 17 is a graph showing activity of an example barrier-forming composition on microbial biofilms after a 1 -min exposure, as described in Examples 80-81.
- Figure 18 presents fluorescent microscopy photographs showing the effect of an example barrier-forming composition on cytopathic effects (CPE) of influenza (H1N1)- infected MDCK cells, as described in Examples 85-86.
- CPE cytopathic effects
- Figure 19 presents fluorescent microscopy photographs showing the effect of an example barrier-forming composition on against H1N1 virus, as described in Examples 85- 86.
- Figure 20 is a graph showing levels of influenza virus in infected barrier-forming composition treated and -untreated cells, as determined by quantitative PCR, as described in Examples 87-88.
- Figure 21 is a graph showing direct antiviral activity of example barrier- forming compositions prepared with or without preservatives and antimicrobial agent (CPC) against influenza virus, determined using quantitative PCR, as described in Examples 89-91.
- CPC antimicrobial agent
- Figure 22 shows the activity of an example barrier-forming composition against H1 1 virus over a 6 hour time period.
- Panel (A) is a graph showing a percent inhibition in viral growth compared to an untreated control.
- Panels (B) and (C) are micrographs of (B) untreated and (C) barrier-forming composition treated cells.
- Figure 23 is a graph showing the activity of formulations against HIV, as described in Examples 94-96.
- Figure 24 is a Western blot showing activity of Example 8 against Epstein-Barr Virus (EBV), as described in Example 97.
- EBV Epstein-Barr Virus
- Figure 25 is a graph showing LDH levels as an indicator of cellular integrity in untreated (control) EHOM or EHOMs tissues exposed to Examples 5-7, as described in Examples 154-159.
- Figure 26 shows representative photographs of a wounded oral epithelial cell culture treated with Example 3 (5% dilution) for 10 minutes, immediately after the wound (panel A), after about 6 hours (panel D), and after about 24 hours (panel E), as described in Example 160.
- Panels B and C show an equivalent wound on an untreated control confluent culture of oral epithelial cells after about 6 hours and about 24 hours, respectively.
- Figure 27 are photographs demonstrating the ability of an example barrier-forming composition to coat the oral mucosal surface.
- Figure 28 are photographs showing time-lapse microscopy of bacterial growth after a 1 minute exposure to an example barrier-forming composition, as described in Examples 162-163. Images represent bacterial growth after 20 min, 120 min, or 360 min post-exposure.
- Figure 29 is a graph showing the effect of a single dose of an example barrier-forming composition on oral microbial burden of a healthy individual, as described in Example 164- 166.
- A - Microbial load in CFUs
- B reduction in microbial load (%) compared to baseline.
- Figure 30 is a graph showing the effect of an example barrier-forming composition on levels of oral microbes over a 5 -day period in three healthy adults, as described in Examples 167-169.
- Figure 31 is a graph showing the effect of an example barrier- forming composition on microbial burden of the oral cavity after 5 -day usage in 31 healthy subjects, as described in Examples 170-198.
- Figure 32 is a graph showing the microbial load in oral samples obtained from three representative study participants, as described in Examples 170-198.
- Figure 33 shows is a schema describing the in vitro filter insert-based model to evaluate penetration of microbes across the barrier formed by example barrier-forming compositions, as described in Examples 199-205.
- Figure 34 is a set of photographs showing growth of MRSA biofilms on the surface of silicone elastomer discs treated with PBS (control, A, C, E) and Example 7 barrier forming composition (B, D, F), as described in Examples 219-224.
- Figure 35 is a set of photographs showing cell monolayers treated with an
- Example 252 for varying time periods (a), (b), and (c), and a control Example 253 (d).
- Figure 36 is a set of immunofluorescence photographs showing cell monolayers treated with an embodiment of the barrier-forming composition, Example 252, for varying time periods (a), (b), and (c), and a control Example 253 (d).
- This application discloses a stable composition for treating/cleaning surfaces that provides a long-term sustained microbial static or cidal activity that inhibits or destroys harmful microbial growth that also has a barrier-forming property.
- the composition is also safe for human consumption.
- the method and composition incorporates an antimicrobial agent that can inhibit microorganisms, including bacteria, fungi, and viruses, known to cause infections.
- the method provides a barrier on a surface by forming a barrier film or coating over it and an antimicrobial agent is included that can kill or inhibit microorganisms (bacteria, fungi and viruses).
- the barrier-forming composition is also effective against microorganisms that cause odor and detraction of the visual aesthetic appearance of surfaces.
- the composition in an embodiment, is safe and non-toxic for such consumption.
- the surface treatment composition would be expected to be safe even if, for example, a child puts their mouth directly on the treated surface and ingests a portion of the composition.
- a utensil or other item that contacts food may be coated with the barrier forming composition and may impart some of the composition to food surfaces that then contact mucosa of a human and become ingested.
- a barrier-forming composition that is non-toxic and safe and forms a barrier that inhibits the passage of active pathogenic microbes through to the other side is desirable. Another desirable property is an ability to inhibit microbial growth through static or cidal activity for an extended period of time.
- the mechanism of action of the barrier-forming composition disclosed herein is based on a synergistic dual- action mechanism, in which germs are trapped in the formed barrier coating, and
- the barrier- forming composition is not hydrophilic, which, without being bound by theory, is theorized to enhance its sustained effectiveness.
- the composition may have adhesive properties for dry surfaces and/or be hydrophobic.
- the properties of the barrier-forming composition and its effectiveness to prevent a wide variety of communicable diseases were assessed using at least ten different approaches based on: (1) an in vitro anti-microbial susceptibility testing; (2) an in vitro time kill assay; (3) an in vitro biofilm model; (4) an in vitro filter insert-based model, (5) an in vz ' vo-like engineered human oral mucosa (EHOM) model; (6) electron microscopy evaluation; (7) hydrophobicity assay; (8) physico-chemical compatibility assays; (9) cell culture -based model using monolayer of human cell lines; and (10) human clinical trials.
- the method and composition described herein may be particularly useful when a human, or more generally, a mammal, has a disrupted skin or mucosa or has a condition resulting in an immunocompromised state or is otherwise at a greater risk for infection.
- a disruption may be caused by a wound, scratch, or other opening in the skin or mucosa.
- the skin and the mucosa of the oral cavity and gastrointestinal (GI) tract serve as an important mechanical barrier that helps to prevent a local or systemic invasion of various microbes and the absorption of microbial products that are normally present in the oral cavity and the lumen of the gut.
- GI gastrointestinal
- a barrier- forming composition that blocks and kills harmful microorganisms and that does not interfere with healing of a disrupted skin or mucosa is a unique and unexpected solution to the susceptibility of the problems of those with disrupted skin or mucosa, particularly those that also have immunodeficiency.
- a barrier-forming composition may be applied in a method for preventing or inhibiting the transfer of microorganisms from the surrounding environment (including from surfaces and airborne particulates that later become deposited on a treated surface) to a mammal.
- prevention it is not meant that no infection from microorganisms is possible, but that the risk of infection from microorganisms encountered at the time of application and/or subsequent to application of the barrier-forming composition is reduced.
- the barrier-forming composition is applied in an effective amount to an inanimate surface and provides a barrier layer on the surface that traps microorganisms, such as by inhibiting microorganisms from penetrating to the other side of the barrier.
- An antimicrobial is provided that kills or deactivates (neutralizes) the microorganism's harmful activity.
- the combined barrier and antimicrobial synergistically act to block, neutralize, and/or kill microorganisms on the inanimate surface or microorganisms that subsequently come into contact with an exposed (top) surface of the barrier, thereby providing a long- lasting antimicrobial that is significantly more powerful than just an antimicrobial alone.
- the barrier is effective to trap and kill or neutralize microorganisms already present on the treated surface and/or to block and kill or neutralize microorganisms that may be deposited on top of the barrier, i.e., the exposed surface of the barrier layer, after the application of the barrier forming composition is performed.
- the barrier layer is active for at least about one hour after application.
- compositions and methods are applicable to various surfaces found in a variety of places, including for example, homes, schools, churches, restaurants, daycares, workplaces, vehicles and medical buildings, such as, for example, ceramic, glass, wood, (including, for example, varnished, stained, or waxed wood), linoleum, CORIAN (a composition of acrylic polymer and aluminum trihydrate), Formica, porcelain, metal (including, for example, stainless steel, steel, iron, wrought iron, copper, brass, bronze, silver, gold, platinum, aluminum, and alloys of such metals), ceramic, painted surfaces, carbon fiber, textile materials (including, for example, wool, silk, cotton, hemp, sisal, velvet, aramid, acrylic, olefins, nylon, rayon, and spandex), concrete, stone (including, for example, granite, marble, soapstone, limestone, Jerusalem stone, quartz, travertine, and slate), plastic, tile, carpet and rubber.
- Types of inanimate surfaces include, for example, countertop,
- Figure 1A is an illustrated flow chart of microbes encountering an untreated inanimate surface (left side) and an inanimate surface with the barrier-forming composition
- barrier layer (right side) that shows a primary efficacy of the barrier-forming composition on an inanimate surface.
- the barrier layer prevents microorganisms from binding to the surface, colonizing and forming a biofilm. Biofilms are known to be difficult to destroy.
- the barrier- forming composition thus presents a surprisingly effective solution to providing a sanitized surface in comparison to cleaners that only focus on killing microorganisms that are only already on the surface. While an antimicrobial solution that does not form a barrier will instantly kill some of the
- the barrier-forming composition prevents biofilms from forming in the first place and also has prolonged activity to destroy already formed biofilms.
- the barrier-forming composition traps and/or kills or neutralizes all harmful microorganisms contacting the barrier- forming composition.
- the barrier substantially traps and/or kills or neutralizes enough harmful microorganisms that contact the barrier-forming composition to inhibit or even stop them from causing an infectious disease. In the latter case, if the harmful microorganism's penetration of the barrier is slowed and/or diluted it will enhance the body's own ability to prevent the microorganisms from causing disease or widespread infection.
- In vitro testing demonstrates that embodiments of the barrier-forming composition prevent all bacteria from reaching the other side of the barrier for long periods, including about two hours or more, about six hours or more, about sixteen hours or more, and about twenty-four hours or more.
- In vitro testing shows that in viruses exposed to embodiments of the barrier-forming composition, growth may be inhibited for about two or more days (such as influenza), up to about nine days, (such as HIV), after which the viral count is still below the MIC for extended periods, such as about two or three additional days. Inhibitory activity against influenza virus was observed for up to 48 hours.
- the barrier-forming composition provides anti-viral activity.
- a virus comes into contact with a cell, it will bind to receptors on the host cell. Over time, 5 to 6 hours, or so, the virus is internalized by the host cell, the virus multiplies inside the host cell, and it induces cell lysis causing additional virus particles to infect other host cells.
- a protective barrier is on the surface of the host cell.
- the barrier may protect the cell and any receptors on the cell, thereby preventing the virus particle from binding to the cell receptors. Thus, infection and lysis is also prevented.
- the disrupted skin or mucosal surface, or a mucosal surface is also protected from bacteria or fungi.
- the barrier-forming composition retains the barrier for a long duration, such as a duration of about 2 hours or more, a duration of about 6 hours or more, a duration of about 16 hours or more, a duration of about 16 hours to about 24 hours, or a duration of about 24 hours or more, thereby protecting host cells and preventing infection.
- the cidal or static antimicrobial activity is also retained for a long duration, such as about 2 hours or more, about 6 hours or more, about 16 hours or more, about 24 hours or more, or about 48 hours or more, thereby killing microorganisms before they can be transferred to mammals and even if transferred to mammals continuing to protect host cells and preventing infection. These durations are applicable for viruses, bacteria, and fungi.
- the barrier-forming composition is applied on an item or apparatus surface prior to the item or apparatus surface encountering a contaminated environment and prior to the apparatus encountering a mucosa of a mammal.
- the barrier- forming composition provides a barrier on the item or apparatus surface that traps and kills the microorganisms, thereby preventing or inhibiting active microorganisms from passing to the mucosa or causing infection.
- Harmful microorganisms are those known to cause infectious disease such as, for example, the treatment and prevention of infectious diseases, such as communicable diseases caused by microorganisms, such as Candida species (e.g. C. albicans, C. glabrata, C. krusei, C. tropicalis), Staphylococcus species (including methicillin-resistant S. aureus, MRSA), Streptococcus species (e.g. S. sanguis, S. oralis, S. mitis, S. salivarius, S. gordonii, S.
- infectious diseases such as communicable diseases caused by microorganisms, such as Candida species (e.g. C. albicans, C. glabrata, C. krusei, C. tropicalis), Staphylococcus species (including methicillin-resistant S. aureus, MRSA), Streptococcus species (e.g. S. sanguis, S. oralis, S. mitis, S. salivarius
- Fusobacterium nucleatum, and other microorganisms such as microorganisms that cause upper respiratory infections, and common cold (rhinovirus) and influenza viruses and Pneumonia, P. gingivalis, Y. enterocolitica, Acinetobacter bumanii, Aggregatibacter actinomycetemcomitans, microorganisms that cause odor, microorganisms that can detract from visual appeal of surfaces, Clostridium difficile, Bordetella pertussis, Burkholderia, Aspergillus fumigatus, Penicillium spp, Cladosporium, Klebsiella pneumoniae, Salmonella choleraesuis, Escherichia coli (0157:H7), Trichophyton mentagrophytes, Rhinovirus Type 39, Respiratory Syncytial Virus, Poliovirus Type 1, Rotavirus Wa, Influenza A Virus, Herpes Simplex Virus Types 1 & 2, and Hepatitis A Virus.
- the barrier-forming composition and method of treatment and prevention described herein may be useful, for example, for prevention of sexually transmitted diseases such as, for example, infections caused by human immunodeficiency virus (HIV), Herpes simplex, or human papilloma virus (HPV).
- HIV human immunodeficiency virus
- HPV human papilloma virus
- the barrier-forming composition has shown effectiveness against microorganisms with a diameter of, for example, about 30 nm or greater, such as about 100 nm (HIV, spherical), about 100 to about 300 nm (influenza, spherical and elongated forms), about 120 nm to about 260 nm (EBV spherical/disk forms), and about 30 nm (rhinovirus, spherical).
- the barrier composition should also be effective against other microorganisms with diameters of about 30 nm, or greater than about 30 nm.
- the barrier-forming composition has even shown powerful and surprising activity inhibiting biofilms, which can be very difficult to eradicate.
- the method comprises administering the barrier-forming composition to a formed biofilm on a surface or inhibiting microorganisms encountered by the barrier coating from forming a biofilm.
- the barrier-forming composition and method of treatment and prevention described herein may be useful, for example, for prevention and/or treatment of odors emanating from microorganisms present on or growing on any of the surfaces mentioned above.
- the barrier-forming composition and method of treatment and prevention described herein may be useful, for example, for the prevention and/or treatment of odors from microorganisms deposited on kitchen or bathroom surfaces, or any other surfaces mentioned herein.
- the barrier- forming composition may be used to prevent odor from bacteria deposited during food preparation, from spills of food or drink or bodily fluids on carpet or vehicle interiors, or any number of other occurrences where odor causing microorganisms are deposited or grow on surfaces.
- Odor causing microorganisms include, for example, bacteria and fungi. Specific examples that may be mentioned, include, Centipeda periodontii, Eikenella corrodens, Enter obacteriaceae, Fusobacterium nucleatum subsp. nucleatum, Fusobacterium nucleatum subsp. polymorphum, Fusobacterium nucleatum subsp. vincentii, Fusobacterium
- the barrier-forming composition and method of treatment and prevention described herein may be useful, for example, for treatment and prevention of detraction of the visual aesthetic appearance of surfaces. Such detraction of the visual aesthetic appearance of a surface may be caused by microorganisms that produce a visible growth on a surface and/or discoloration of a surface.
- the barrier- forming composition and method of treatment and prevention described herein may be useful, for example, for prevention and/or treatment of staining of tile grout by mold, or prevention and/or treatment of basement floor or wall surfaces.
- Microorganisms that cause detraction of the visual aesthetic appearance of surfaces include, for example, fungi. Microorganisms that cause detraction of the visual aesthetic appearance of surfaces may also be considered harmful microorganisms for purposes of this application.
- the microorganisms may be air-borne microorganisms.
- the microorganisms are those that cause communicable diseases.
- the microorganisms do not include those that cause allergic reactions or dental problems, such as, for example, cavities (caries), gingivitis, or seasonal allergies.
- the method of prevention does not solely or additionally prevent dental problems or allergic reactions, such as, for example, cavities (caries), gingivitis, or seasonal allergies.
- microorganisms such as fungi that may generally be classified as allergens, other allergens, and airborne irritants to the mucosa, are blocked by the barrier and the method. It may be especially useful to treat surfaces with the barrier composition if an allergic mammal is expected to be in a location known or expected to produce a high number of allergens or airborne irritants, such as an outdoor environment.
- the methods and compositions disclosed herein may be especially applicable for treating surfaces that immunocompromised persons will encounter.
- the barrier- forming composition may be useful for prevention and/or treatment of infections by microorganisms that commonly infect wounds on the mucosa or skin.
- the barrier-forming composition and method of treatment and prevention described herein may be useful, for example, for prevention and/or treatment of infections from items that may be contaminated in activity related treatments, such as, for example, ventilator use (which would include medical devices related to the ventilator and contacting the patient).
- activity related treatments such as, for example, ventilator use (which would include medical devices related to the ventilator and contacting the patient).
- a contaminated item treatment and prevention of fungal infections through applications to the body, and or items or surfaces coming into contact with the body, such as shoes, may also be mentioned.
- the contaminated item may be, for example, a food, a drink, utensils, drink containers and accessories, an item for use by children, a medical apparatus, or a dental apparatus.
- the interior surface of an apparatus protecting the feet is treated with an effective amount of the barrier-forming composition to destroy, inhibit or prevent odor from fungal growth.
- the shoe may be treated proactively by administering the composition prior to a person wearing the shoe.
- the shoe may be treated prior to a person exercising or participating in an activity where their feet or shoes may become wet.
- the shoe is treated when a person knows that they have a fungal condition on their foot, such as athelete's foot (tinea pedis).
- the shoe may be treated if it is producing a foul odor.
- the barrier-forming composition traps and kills or prevents fungal or other microbial growth, thereby reducing the risk of infection on the human's foot and masking and/or neutralizing the foul odor produced by the microorganisms.
- the surface of a medical device is treated with the barrier-forming composition prior to contacting the human body.
- the barrier-forming composition provides a coating on the medical device surface that traps and kills microorganisms.
- Medical devices include, for example, instruments, apparatuses, and other articles of manufacture that are intended to contact or come in close proximity with the human body, such as human tissue, bloodstream, mucosa, open wounds, and internal cavities.
- medical devices include ventilators, trachea devices, catheters, central venous catheters, urinary catheters, peritoneal dialysis catheters, contact lenses, total joint replacement prostheses, endotracheal tubes, voice prostheses, penile prostheses, testicular prostheses, prostatic stents, artificial urinary sphincters, breast prostheses, vascular graft, orthopedic devices, prosthetic heart valves, scalpels, scopes, implanted replacement devices, In an embodiment, medical devices also include dental devices.
- the medical device is treated with the barrier-forming composition prior to encountering the human body, such as up to about 12 hours prior to encountering the human body, for example, about 5 minutes to about 8 hours, about 12 minutes to about 6 hours, or about 1 hour to about 10 hours, prior to encountering the human body.
- the medical device is treated with the barrier forming composition in a spray formulation by spraying the medical device until a moist coating appears on the surface.
- the medical device is treated by dipping the medical device in the barrier-forming composition and withdrawing it from the composition, which results in a residual coating layer on the medical device.
- the medical device is a catheter or similar device that is inserted into a mammal body canal, such as the throat, the anal, vaginal, or urethral canals.
- the coating is applied to the medical device prior to encountering the body canal and, as it is inserted, also helps to lubricate the body canal and provide antimicrobial activity along the canal.
- the medical device is an implanted device, such as a replacement hip part. The coating is applied to the medical device prior to encountering the body canal and provides a long-lasting and powerful antimicrobial barrier, thereby guarding against microorganisms that were on the medical device prior to the treatment and also any microorganisms that encounter the medical device after the treatment.
- the medical device that contacts more than one location on the body such as a catheter, scope or a device used in surgery. Treating such a medical device prior to the first contact with the body may reduce the risk of transferring infectious microorganisms from one area of the body to another.
- the method of treating a surface with the barrier forming composition includes identifying a contaminated surface, wherein the contaminated surface is known or expected to be contaminated with harmful viral, fungal, or bacterial
- the step of applying the barrier-forming composition occurs prior to or during a mammal that is not contaminated encountering the contaminated surface.
- the application of the barrier-forming composition occurs in response to the identification of the surface as being contaminated or in response to an observation of a contamination event.
- the barrier composition may be applied to a surface where a contamination event has occurred, such as when a person has sneezed, coughed, or vomited, or more generally where bodily fluids or matter have been deposited.
- the barrier-forming composition is applied on a mucosa, such as an oral, pharyngeal, or nasal mucosa, in response to encountering an environment that is considered to be contaminated or in response to an observed contamination event.
- the barrier-forming composition provides a barrier coating on the mucosa surface that traps and kills microorganisms, such as those that are encountered subsequent to the application of the barrier-forming composition, thereby preventing or inhibiting active microorganisms from passing to the mucosa or causing infection.
- the method of treating a surface with the barrier forming composition includes identifying a contaminated surface, wherein the contaminated surface is known or expected to be contaminated with odor causing viral, fungal, or bacterial microorganisms.
- the step of applying the barrier-forming composition occurs prior to or during an odor emanating from the contaminated surface.
- the barrier composition may be applied to a surface where food is handled or bodily fluids are deposited, or any of the surfaces listed herein.
- a method includes preventing or decreasing odor produced by microorganisms, by performing the steps of applying a barrier-forming composition that comprises an antimicrobial onto an inanimate surface.
- the barrier-forming composition then quickly forms a barrier layer on the inanimate surface that is active to trap, and kill or neutralize microorganisms encountered by the barrier layer for a duration of at least about one hour, thereby preventing or decreasing odor generated by microorganisms from escaping the barrier layer.
- the microorganisms that encounter the barrier layer may be those that were already present on the surface that was treated or those that are disposed on the exposed top surface of the barrier layer after it is applied.
- the method includes identifying an area of the inanimate surface that is a source of the odor, and applying the barrier-forming composition to the area.
- the method of treating a surface with the barrier forming composition includes identifying a contaminated surface, wherein the contaminated surface is known or expected to be contaminated with viral, fungal, or bacterial microorganisms that cause detraction of the visual aesthetic appearance of surfaces.
- the step of applying the barrier-forming composition occurs prior to, during, or after a detraction of the visual aesthetic appearance of the contaminated surface occurs.
- the barrier composition may be applied to bathroom tile grout that show visual signs of mold growth or are expected to come in contact with mold, or on other surfaces mentioned herein that show visual signs of mold growth or are expected to come in contact with mold.
- the method includes preventing or treating a detraction of a visual appearance of a surface, where the detraction is caused by microorganisms that produce a visible growth on the surface or discoloration of the surface.
- the treatment or prevention is facilitated by the steps of applying a barrier-forming composition that comprises an antimicrobial onto the surface; forming a barrier layer on the surface that is active to trap, and kill or neutralize microorganisms encountered by the barrier layer for a duration of at least about one hour, thereby preventing or decreasing the visible growth or discoloration on the surface.
- the microorganisms that encounter the barrier layer may be those that were already present on the surface that was treated or those that are disposed on the exposed top surface of the barrier layer after it is applied.
- the method includes identifying an area of the surface that has a visible microbial growth or discoloration, and applying the barrier-forming composition to the area.
- the method of treating a surface with the barrier forming composition includes treating the surface with the barrier-forming composition proactively, regardless of whether the surface is known or expected to be contaminated with viral, fungal, or bacterial microorganisms.
- the administered barrier coating traps and kills microorganisms that encounter the barrier coating after the treating step.
- the barrier coating is effective to kill microorganisms encountered for a long duration after the treatment step, thereby facilitating its effectiveness as a proactive treatment, which stands in contrast to prior art antimicrobial compositions that are not effective for proactive treatment, partly due to their ineffectiveness for long time-periods.
- the method of treating a surface with the barrier forming composition includes treating a food surface with the barrier forming composition.
- the method of treating a food surface with the barrier forming composition includes identifying a possibly contaminated food surface or a contamination event occurring in the vicinity of the food surface, wherein the surface is known or expected to be contaminated with harmful viral, fungal, or bacterial microorganisms or be exposed to the same.
- the food surface may be selected from produce, such as fruits and vegetables, including for example, salad vegetables, lettuce, cabbage, onions, spinach, broccoli,carrots, brussel sprouts, potatoes, nuts, carrots, apples, oranges, bananas, berries.
- the food surface may include meat, such as, for example, raw meat including, for example, beef, pork, lamb, chicken, and turkey.
- the food surface may also include processed meats, such as bologna, salami, pepperoni, and frankfurters.
- the barrier-forming composition may be applied to a food surface that is deemed to have a heightened risk of e. coli, salmonella, botulism, or listeria.
- the heightened risk may be based on knowledge of prior infections of a certain type of food surface or known contaminations of food surfaces in a common locality.
- the heightened risk may be based on a known or expected exposure of the food surface to a contaminant.
- the food surface treated in response to a contamination event such as a person sneezing or coughing in the vicinity of the food surface.
- a contamination event such as a person sneezing or coughing in the vicinity of the food surface.
- a contamination event such as a person sneezing or coughing in the vicinity of the food surface.
- a contamination event such as a person sneezing or coughing in the vicinity of the food surface.
- a contamination event such as a person sneezing or coughing in the vicinity of the food surface.
- a contamination event such as a person sneezing or coughing in the vicinity of the food surface.
- the food surface may be treated proactively to prevent contamination of microorganisms that may contact the food surface after the treatment, such as for up to 24 hours after treatment, or between about 12 minutes to about 6 hours, or between about 1 hour to about 8 hours post-treatment.
- produce that is available to be touched by numerous customers such as in a supermarket or salad bar, may be treated proactively with the barrier composition in the anticipation of guarding against a contamination event or contaminated environment.
- the barrier composition in the anticipation of guarding against a contamination event or contaminated environment.
- the barrier composition is rinsed off prior to consumption.
- the barrier composition is safe for human consumption in the therapeutically effective amount and is not rinsed off the food surface prior to consumption.
- the proper amount to apply to a surface is an amount that is enough to coat the targeted surface with enough of the barrier-forming composition to form a barrier layer, for example, this may be determined by whether the surface appears wet or misted.
- the effective amount for a may be expressed in terms of a volume per square cm, such as, for example, from about 0.5 to about 50 ⁇ /cm 2 , such as, about 5 to about 40 ⁇ /cm 2 , or about 10 to about 25 ⁇ /cm 2 ; or for example, about 0.625 to about 10 ⁇ /cm 2 , such as, about 2.5 to about 5 ⁇ /cm 2 .
- Other delivery mediums, such as a roll-on or disposable wipes may have dosages derived from these ranges given the adjustments for concentrations and other factors known to those of skill in the art.
- the average thickness of the film formed on the surface from the barrier- forming composition may range, for example, from about 0.001 to about 0.2 mm, such as about 0.01 mm to about 0.1, or about 0.08 to about 0.15 mm.
- the barrier-forming composition in a continued application method of prevention and/or treatment, may be administered to a surface in a series of doses, such as, for example, about every 1 to 2 days, about every 2 to 4 days, or about every 1 to 2 weeks.
- This method of prevention and/or treatment can be continued, for example, for 6 to 12 months or for several years.
- This continued application method may be preferred during flu season or outbreaks of particular illnesses, or simply as part of a routine cleaning schedule.
- methods of applying the barrier-forming composition include, for example, rubbing, mopping, wiping, or spraying the composition onto the surface.
- the barrier-forming composition may be applied to the surface through many different delivery systems, including, for example: dilutable liquids, gels, lubricants, compositions sprayable by a mechanical action pump, aerosolized spray compositions, or infusion or layering of the barrier-forming composition into or onto products, such as disposable wipes.
- the composition is sprayed onto a surface in an amount sufficient to coat the surface with a mist or thin layer of liquid.
- One or more sprays may be required to coat the surface depending on the size of the surface. Areas that are considered especially contaminated with microorganisms may be treated more heavily than others. Wiping or rubbing is not required in this embodiment.
- a mechanical pump spray or an aerosolized spray device may be used.
- the barrier-forming composition may be mixed with common propellant agents, such as CO 2 , nitrogen, and hydrocarbons.
- a bag-on-valve embodiment may also be used; however, the composition is stable enough so as not to require a separation of the propellant agent and the composition components.
- the barrier-forming composition is applied by wiping the composition onto the surface from a material that includes the barrier-forming composition.
- a material that includes the barrier-forming composition For example, a cloth, a mop, a scrubbing brush, a toilet cleaning brush, or a paper towel, may be at least partially saturated with the barrier-forming composition.
- the composition may then be wiped or mopped or otherwise applied to the surface from the material.
- the composition can be applied by spraying and subsequent wiping of the sprayed composition.
- a disposable wipe is pre-treated with the barrier-forming composition.
- the wipe can simply be removed from a container and then be rubbed on the desired surface to apply the barrier-forming composition to the surface.
- the wipe can then be disposed of.
- Common materials for disposable wipes include, for example, wood pulp, viscose, polyester, cotton, and combinations of these.
- the wipe can be soaked in and then removed from the barrier forming composition for the pre-treatment step.
- the wipe should be at least partially saturated with the barrier forming composition.
- the surface should be wetted with the wipe to provide an effective barrier.
- a barrier-forming composition is deposited that forms a thin film barrier on the surface and is active to inhibit microorganisms from passing through the barrier layer.
- the disposable wipe may be used to treat an item, such as a utensil, in order to apply the barrier-forming composition to the utensil.
- the barrier-forming composition comprises a carbohydrate gum (C), a humectant (H), and an antimicrobial agent (A), and the barrier-forming composition meets the following requirements:
- the barrier layer has antimicrobial cidal or static activity.
- barrier-forming composition meets the following requirements:
- the humectant of the barrier-forming composition meets the following requirements: about 0.07% ⁇ H ⁇ 1%. This low-humectant embodiment reduces the stickiness or adhesiveness of the composition to provide a better tactile sensation to the inanimate surface.
- the barrier-forming composition includes glycerin or one or more similar humectant substances.
- the concentration of the humectant may range from about 0.07% to about 10% of the entire composition (by weight), such as about 3% to about 8%, 0.35% to less than 1%, or about 0.1% to less than 0.5%.
- the humectant may range from about 2% to about 70% weight percent of the entire composition, such as, for example, about 4.5% to about 65%, about 7% to about 35%, or about 15% to about 45%.
- Humectants similar to glycerin may be classified generally as polyols.
- the humectants may be, for example, glycerin, sorbitol, xylitol, propylene glycol, polyethylene glycol, and mixtures thereof.
- glycerin may be used at high concentrations such as about 55% to about 65% in the absence of a gum.
- the composition also includes a gum.
- the gum may be, for example, a polysaccharide, xanthan gum, gum Arabic, or guar gum. Such gums may be generally classified as carbohydrate gums that have an overall negative charge.
- the gum may be, for example, xanthan gum, guar gum, gum Arabic, tragacanth, gum karaya, locust bean gum, carob gum, and pectin. These gums may also be generally classified as carbohydrate gums that have an overall negative charge.
- the gum may be present in a weight percentage of the total composition ranging from about 0.0001% to about 0.4%, such as about 0.0005 to about 0.25%.
- the gum may be present in a weight percentage of the total composition ranging from about 0.01% to about 0.4%, such as for example, about 0.25% to about 0.35%, about 0.05% to about 0.25%, or about 0.4%.
- the barrier composition comprises a humectant, an antimicrobial, and optionally a gum, wherein the gum, if present, is present in an amount of about 0.0001% to about 0.4% by weight of the total barrier-forming composition.
- an antimicrobial agent is present in the composition.
- the composition may include one or more anti-viral agents, or antifungals or antibacterials or a combination thereof.
- the effect of such antimicrobials includes static and/or cidal activity.
- the antimicrobial agent may include, but is not limited to cationic antimicrobial agents and pharmaceutically acceptable salts thereof, including, for example, monoquaternary ammonium compounds (QAC, cetrimide, benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, Polycide), biquaternaries and bis- biguanides (Chlorhexidine, Barquat, hibitane), and biguanides, polymeric biguanides, polyhexamethylene biguanides, Vantocil, Cosmocil, diamidines, halogen-releasing agents including chlorine- and iodine-based compounds, silver and antimicrobial compounds of silver, peracetic acid (PAA), silver sulfadiazine, phenols, bisphenols, hydrogen peroxide, hexachloroprene, halophenols, including but not limited to chloroxylenol (4-chloro-3,5- dimethylphenol;
- PAA
- the antimicrobial may also be or include: antibacterial agents, both cidal and static, and different classes, for example tetracycline, chloramphenicol, fusidic acid, fluoroquinolone, macrolide antibacterial agents, oxazolidinones, quinolone- and
- the antimicrobial may also include, for example: antifungal agents in the following classes: azoles, polyenes, echinocandins, and pyrimidines. Combinations of the any of the foregoing antimicrobial agents are also contemplated. Many of the foregoing are cationic species or their pharmaceutically acceptable salts, and in an embodiment, cationic antimicrobials are utilized in the composition.
- the composition is exclusive agents that release gas fumes, such as, for example, chlorine dioxide, or chlorine dioxide producing reactants.
- the barrier-forming composition does not induce mutations or the development of resistance by microbes. This is because of the mechanism of action against the microorganisms by the barrier and the selected antimicrobial.
- the antimicrobial may be present, for example, in an amount ranging from about 0.0005% to 5% by weight of the total composition, such as, for example, about 0.0025% to about 1%, about 0.005 to about 0.006%, or about 0.0006% to about 0.003%.
- the antimicrobial may be present, for example, in an amount ranging from about 0.05% to about 0.1% by weight of the total composition, such as, for example, about 0.05% to about 0.06% or about 0.06% to about 0.1%.
- the antimicrobial is about 5% or less, or about 3% or less, or about 1.5% or less, such as when the antimicrobial used does not cause solubility problems at higher concentrations.
- the composition may further include other components, such as, for example, copovidone and other lubricating agents, parabens such as methyl paraben or propylparaben, scenting agents, preservatives, such as sodium benzoate, buffering agents, such as monosodium and disodium phosphate, sweeteners, hydrogenated castor oil with ethylene oxide, and carboxymethylcellulose.
- these components may, for example, be included in amounts ranging from about 0.01% to about 5% by weight of the total composition, such as, for example, about 0.1% to about 2%. In another embodiment, the components are included, for example, in amounts of about 0.0001% to about 0.05%.
- Buffering agents such as monosodium or disodium phosphate may also be used.
- the barrier-forming composition is a free -flowing liquid suitable for spraying. This is in contrast to a paste or toothpaste composition, which is typically not free-flowing and not suitable for spraying.
- the barrier-forming composition is free of abrasives that are commonly used in toothpaste compositions.
- the composition consists essentially of only the gum, the humectant, and the antimicrobial, such as including only preservatives or scenting agents that do not affect the barrier or antimicrobial activity.
- the composition is exclusive of agents for acting against the teeth and/or gums, including, for example, abrasives (such as those used in toothpastes) teeth whitening or desensitizing agents.
- the composition is exclusive of cellooligosaccharides.
- the antimicrobial agent is exclusive of lipids such as fatty acid ethers or esters of polyhydric alcohols or alkoxylated derivatives thereof.
- the composition is exclusive of one or more of time-release agents, allergy-relief compounds, azelastine, silicon based oils, essential oils, polyvinyl pyrrolidone, polyvinyl alcohol, and potassium nitrate.
- the composition is free of volatile organic compounds, including for example, volatile alcohols.
- the composition is free of surfactant or foaming agent.
- a method for making a barrier-forming composition includes mixing and heating the carbohydrate gum, humectant, and antimicrobial agents. In an embodiment, heating is replaced with extended mixing times. Other components may also be mixed in a single or multiple mixing steps. All components of the barrier-forming composition may be mixed at one time to produce a composition with a stable shelf life. This is in contrast to compositions that have active components that must be added separately a short time prior to use. Thus, in an embodiment, the barrier-forming composition is a stable one-part composition that does not require mixing with a second composition to activate it for use.
- the dual-action mechanism of providing a barrier from microorganisms and an antimicrobial agent provides a long-lasting effect, characterized by both in vitro, simulated in vivo, and in vivo examples below.
- the barrier-forming composition was shown to have antimicrobial effect (cidal or static) for at least 6 hours, while the barrier property was tested in simulated in vivo tests (on artificial human mucosa
- EHOMs indicated the barrier itself had a significantly extended duration past 6 hours, such as greater than about 8 hours, about 6 to about 16 hours, and about 24 hours, or more.
- in vitro tests indicate the antimicrobial effect had a significantly extended duration past about 2 hours, past about 6 hours, and depending on the microorganism tested, such as greater than about 8 hours, about 6 to about 16 hours, and about 24 hours, or more.
- Post antimicrobial effect is defined as suppression of microbial growth that persists after limited exposure to an antimicrobial agent. Having a longer PAE is considered advantageous for antimicrobial agents as it allows for persistent inhibition of microbial growth, and may affect dosing regimens as agents with long PAEs may need less frequent administration than those with short PAEs.
- the PAE of the composition when applied to a mucosa has a PAE that persists for about 6 hours or more, such as about 6 hours to about 16 hours, or about 16 hours to about 24 hours.
- the composition is liquid and is non-foaming.
- the composition is suitable for spraying, and thus also has a viscosity that is suitable for spraying.
- the composition has a viscosity of less than 500 cps such as, for example, about 490 cps to about 10 cps, or about 400 cps to about 15 cps.
- the composition has a viscosity of about 16 to about 20 cps, such as, for example, about 17 to about 19 cps.
- the composition is non-toxic to humans, wherein at least a portion of the composition may be ingested and is safe for human consumption.
- the barrier-forming composition is not hydrophilic which allows the barrier-forming composition to have a greater affinity to adhere to and cover certain surfaces. Furthermore, in an embodiment, the antimicrobial being embedded in the non-hydrophilic composition will allow for sustained antimicrobial activity on treated surfaces. In an embodiment the barrier-forming composition is amphiphilic or has amphiphilic components.
- composition has an Rf value in water of 0 to about 0.25, such as about 0.0001 to about 0.15, or about 0.03 to about 0.1.
- the composition has a pH of about 4 to about 8, such as about 5 to about 7, or about 6 to about 7.5. In another embodiment the composition has a pH of greater than 5.5 to about 8, wherein antimicrobials such as cetylpyridinium chloride are most effective.
- the barrier-forming composition has been shown to trap and block the passage of a wide variety of representative fungi, bacteria and viruses. Because viruses are amongst the smallest infectious microorganisms, and because the barrier- forming composition forms a mechanical barrier blocking viruses, it is expected that the barrier-forming composition would be an effective preventative treatment not only for viruses but also for larger microorganisms, including a wide range of bacteria and fungi.
- fibroblasts Normal human gingival cells (epithelial cells and fibroblasts) were obtained from ScienCell Research Laboratories (Carlsbad, CA, USA). The fibroblasts were cultured in Dulbecco's modified Eagle's medium (DME, Invitrogen Life Technologies, Burlington, ON, Canada) supplemented with fetal bovine serum (FBS, Gibco, Burlington, ON, Canada) to a final concentration of 10%.
- DME Dulbecco's modified Eagle's medium
- FBS Gibco, Burlington, ON, Canada
- the epithelial cells were cultured in Dulbecco's modified Eagle's (DME)— Ham's F12 (3 : 1) (DMEH) with 5 ⁇ g/mL of human transferrin, 2 nM 3,3',5' of tri- iodo-L -thyronine.
- DME Dulbecco's modified Eagle's
- EDTA ethylenediaminetetra acetic acid
- the EHOM model was produced by using the gingival fibroblasts and epithelial cells of Example 1 that were used to form a complex three-dimensional spatial cellular organization similar to that found in normal human oral mucosa.
- the lamina basement membrane was produced by mixing Type I collagen (Gibco-Invitrogen, Burlington, ON, Canada) with gingival fibroblasts, followed by culture in 10% FBS-supplemented medium for four days. The lamina intestinal was then seeded with gingival epithelial cells to obtain the EHOM.
- the tissue specimens were grown under submerged conditions until the total surface of the lamina intestinal was covered with epithelial cells.
- the EHOM was raised to an air-liquid interface for four more days to facilitate the organization of the epithelium into its different strata.
- the lamina basement membrane is a thin layer of loose connective tissue that lies beneath the epithelium and together with the epithelium constitutes the mucosa.
- Figure 2 shows an illustration of the EHOM mucosal tissue, with an arrow pointing to its location in a schema depicting mucosa covered with the barrier-forming composition.
- barrier-forming compositions were created by adding the ingredients listed below in a 50-mL centrifuge tube, and vortexing to bring to "free-flow" consistency.
- the constituents of the compositions and their approximate amounts are given in Table I (the values in Table I are percentages by weight of the total composition):
- Wound repair assays were performed on the epithelial cells and fibroblasts of Example 1. Briefly, gingival epithelial cells (lxlO 4 cells) and fibroblasts (lxlO 3 cells) were seeded into wells of 6-well plates and grown in Dulbecco's modified Eagle's (DME) - Ham's F12 (3 : 1) (DMEH) with 5 ⁇ g/mL of human transferrin, 2 nM 3,3',5' of tri-iodo-L -thyronine, 0.4 ⁇ g/mL of hydrocortisone, 10 ng/mL of epidermal growth factor, penicillin and streptomycin, and 10% FBS (final concentration). Upon confluency, wounds were made in the confluent monolayer of each well using a 200 pipette tip.
- DME Dulbecco's modified Eagle's
- Example 11 and 12 the epithelial cell cultures from Example 10 were exposed to diluted barrier-forming compositions of Examples 3 and 4 for about 2 minutes.
- the fibroblast cultures from Example 10 were exposed to diluted barrier-forming compositions of Examples 3 and 4 for about 2 minutes.
- Example 3 Prior to exposure, Example 3 was diluted with saline to a 1% concentration and Example 4 was diluted with saline to a 5% concentration.
- the spray was washed out twice with warm sterile culture medium, then cell cultures were over layered with DME for fibroblasts and DMEH for epithelial cells, and cultured for 6 and 24 hours in a 5% CO 2 humid atmosphere at 37°C. Control Example 15, which was an untreated culture from Example 10, was also tested.
- Figure 3 shows a graph of the wound repair data generated from formula I after 6 hours post-treatment.
- Figure 4 also shows photographs indicating the wound repair of the epithelial cells cultures treated with the 1% diluted barrier-forming composition and the control Example 15.
- Example 16 and 17 The engineered human oral mucosa (EHOM) model of Example 2 was used to determine whether the composition of Examples 10 and 11 were safe and did not promote tissue damage or cell necrosis.
- the epithelium surface (10 cm 2 ) was over layered with a thin layer (300 ⁇ ) of the Example 3 barrier-forming composition at a dilution of 5% and the Example 4 composition at a dilution of 1% (both were diluted in serum free culture medium) for time periods of about 2 minutes. The variation in time period was not deemed to have an effect on the results and just reflects the time it took to conduct the procedures.
- Control Example 18 was a control that was not treated with the barrier- forming composition.
- EHOM tissues were then rinsed twice with warm sterile culture medium and incubated in a 5% CO 2 humid atmosphere at 37°C for 24 hours. Following this incubation period, to assess whether the engineered tissue was damaged, each EHOM was macroscopically examined for the presence of holes due to the contact with the barrier spray formulation. Photos were taken of these EHOM to confirm such possibility. Additionally, biopsies were collected from each EHOM and subjected to histological staining using eosin and hematoxylin.
- Example 7B compositions. This was confirmed by histological analyses showing multilayer organisation of the epithelium on the top of a fibroblast-populated connective tissue. No specific damage was observed in EHOM tissues in Examples 16 or 17.
- Figure 5 shows the effect of the barrier-forming composition on EHOM macroscopic shape and structure.
- Panels A and B show control Example 18.
- Panels C and D show
- Example 16 (spray composition) and panels E and F show Example 17 (mouthwash composition).
- LDH cytotoxicity assay Promega, Madison, WI, USA
- This assay measures the conversion of L- lactate and NAD to pyruvate and NADH by the released LDH.
- 50 ⁇ of stop solution was added to each well.
- 100 ⁇ of the mixture were transferred to a 96- well flat-bottom plate, and the absorbance was read at 490 nm with an X-Mark microplate spectrophotometer (Bio-Rad, Mississauga, ON, Canada).
- EHOMs of Example 2 were treated with Example 4 for about 2 minutes, washed with culture medium then cultured for 24 hours. Tissue was then examined for possible macroscopic tissue damage (presence or not of holes). Tissue damage was also investigated by histological analyses. For this purpose, biopsies were taken from each EHOM. They were fixed with 4% paraformaldehyde solution and then embedded in paraffin. Thin sections (4 ⁇ ) were stained with eosin-hematoxilyn. Sections were mounted with a coverslip in 50%-glycerol mounting medium, observed through an optical microscope, and photographed. No damage to the treated EHOMs was ascertained.
- Example 27 and 28 two approaches were used to determine whether the control Examples formed a barrier that blocked the microbial passage through the mucosal tissues and also had an inherent anti-microbial effect. Growth in pass-through chamber and growth on EHOM surface was assessed by evaluating growth in agar media.
- Example 27 EHOMs of Example 2 were put in contact with 1 and 5% dilutions (diluted in serum free culture medium) of Example 4 for 2 minutes. Tissues were then washed twice with serum free culture medium then over layered with lxlO 6 Candida microbial cells in a volume of 300 ⁇ . Tissues were then put on air-liquid culture plates and incubated for 24 hours in 5% CO 2 humid atmosphere at 37°C. Next, the culture medium underneath the EHOM (ventral chamber) was collected and seeded on Sabouraud agar plate to verify whether or not the microorganisms penetrated through the tissue and reached the culture medium below. A culture was also obtained from the EHOM surface and seeded on Sabouraud agar plate. The process is graphically depicted in Figure 7.
- Example 28 EHOMs of Example 2 that were treated with 1 and 5% dilutions of the Example 4 composition for 2 minutes were over layered with Candida microbial cells for 24 hours were flipped onto Sabouraud dextrose agar plates and left in place for 5 minutes. The EHOMs were then removed and the plates were incubated for 24 hours at 30°C, after which microbial growth was ascertained macroscopically and photographed. Each experiment was repeated 5 independent times with similar results.
- Figure 8 shows the results of the cultures of the EHOM surface (panels C and D) and the culture of the pass-through liquid from the bottom (ventral) chamber (panels A and B).
- the A and C panels were EHOMs treated with a 1% dilution of Example 4, and the B and D panels were EHOMS treated with a 5% dilution of Example 4.
- This data indicates that Example 4 composition forms a barrier that prevents passage of microbes through the EHOM tissues but does not have an inherent anti-microbial effect.
- Examples 29 and 30 [197] In Examples 29 and 30, Examples 27 and 28 were repeated, except the EHOM were infected with S. mutans. Similar results were obtained that indicated that the barrier-forming compositions formed a barrier preventing the S. mutans microbes from passing through the barrier, but did not have an antimicrobial effect.
- Example 32 a set of EHOM tissues from Example 2 was treated with the barrier- forming composition of Example 4 and then overlaid with C. albicans.
- control Example 31 a control set was not treated with the barrier-forming composition prior to overlayering with C. albicans.
- biopsies were taken from each EHOM, fixed with paraformaldehyde solution, and embedded in paraffin. Thin sections (4 ⁇ ) were stained with eosin-hematoxylin. Sections were observed using an optical microscope to analyze the invasion/penetration of microbial cells into the tissue. Following microscopic observations, representative photos were taken from each condition and presented. The experiment was repeated three times with similar results. Similar results were also obtained with treatment with Example 3 (data not shown).
- Figure 9 shows the effect of the barrier-forming composition on microbial invasion of EHOM tissues.
- Panel (A) is a representative photograph of the untreated control Example 31, and panel (B) is a photograph of the treated Example 32.
- the arrow indicates invading fungal hyphae in the untreated control Example 31.
- the EHOM model described above was also used to evaluate the ability of Examples 5-7 to form a barrier that: (a) prevents oral bacteria (S. mutans) and fungi (Candida albicans) from penetrating/invading human oral mucosa, and (b) does not cause damage to host cells (cytotoxicity assay).
- Examples 33-40 were formulated according to Table III below.
- Example 35 Example 6 C. albicans Fig. 10(C)
- Example 36 Example 7 C. albicans Fig. 10(D)
- Example 38 Example 5 S. mutans Fig. 11(B)
- Example 39 Example 6 S. mutans Fig. 11(C)
- Example 40 Example 7 S. mutans Fig. 11(D)
- Examples 33-40 after pre-treatment and incubation according to the procedures of Examples 27 and 28: (1) the flow-through medium was collected from the lower chamber; and (2) tissues were flipped and placed onto the surface of Sabouraud dextrose agar Petri dishes, and incubated for 24 hours. Collected flow-through media were spread onto agar media plates, and incubated for 24 hours also as described in Examples 27 and 28. Table III also indicates the Figure in which a photo of each Example was taken showing the microbial growth on each flipped Example culture.
- FIGS 10 and 1 1 show that both Candida and Streptococcus were able to grow on the surface of EHOM treated with the compositions of Examples 5-6.
- Figure 12 no microbial growth was observed when the "flow-through" medium collected from the lower chambers of EHOMs of Examples 36 or 40, i.e. those treated with the Example 7 composition. This indicates that treatment of the EHOMs with the Example 7 composition did not cause damage to the surface of the mucosal tissues and organisms were unable to penetrate the treated EHOM.
- Similar results were obtained with EHOM treated with the compositions of Examples 5 and 6 (data not shown). These data indicate that the combination of glycerine and xanthan gum is capable of forming a protective barrier on mucosal tissues.
- Tested Formulations are not Toxic and do not Cause Damage to the Cells/Tissues
- the EHOM model was used to assess the toxicity of the composition. Examples 41-47 were formulated as stated in Table IV.
- Example 42 Example 5 C. albicans Fig. 13(A)
- Example 43 Example 6 C. albicans Fig. 13(A)
- Example 44 Example 7 C. albicans Fig. 13(A)
- Example 45 Example 5 S. mutans Fig. 13(B)
- Example 46 Example 6 S. mutans Fig. 13(B)
- Example 47 Example 7 S. mutans Fig. 13(B)
- compositions represent an effective and a safe barrier that can prevent microorganisms from penetrating and invading human mucosal tissues.
- Example 7 barrier-forming composition was effective against many bacteria and yeasts.
- the antimicrobial activities of the Example 7 barrier-forming composition were evaluated against a number of clinical isolates obtained from patients, including S. salivarius, P. gingivalis, S. pyogenes, S.
- Example 7 barrier-forming composition Activity of the Example 7 barrier-forming composition was evaluated by determining its minimum inhibitory concentration (MIC) using reference methods described in the Clinical and Laboratory Standards Institute (CLSI) documents M07-A8, Ml 1-A7, and M27-A3.
- CLSI Clinical and Laboratory Standards Institute
- the barrier-forming composition was also found to have potent antimicrobial activity against: MRSA, Acinetobacter baumannii, Streptococcus sanguis, S. gordonii, and
- Example 7 composition exhibited potent activity against many aerobic and anaerobic bacteria, as well as the fungi.
- Example 7 barrier-forming composition against X oralis and S. mitis was noticeably elevated (500 ⁇ g/mL) compared to other organisms. It is interesting to note that S. oralis and S. mitis are normal commensals of the oral cavity. Activity of the commonly used antimicrobial chlorhexidine (2% solution) was also determined by the same method. Table V shows the MIC of the Example 7 barrier-forming composition and chlorhexidine (2% solution) as a comparative example against various microorganisms.
- Example 7 possesses potent activity against pathogenic bacteria and fungi commonly isolated from the oral cavity. This activity was more potent than that observed for chlorhexidine.
- Example 8 The PAE of Example 8 against several microorganisms was evaluated in Examples 63-68.
- Control Example 69 was also provided. Several microorganisms were exposed to Example 8 (at a concentration equal to the MIC) for 1 min followed by three washes to remove residual formulation. The treated cells were then spread on agar medium plates, which were incubated at 37 °C, and the time taken for the cells to re grow was determined. PAE was expressed as the time (in hours) for which growth inhibition (%) was maintained by the Examples 63-68, compared to the untreated control Example 69.
- Example 8 exhibited a PAE ranging between 4 hours to 24 hours, depending on the organism tested (S. aureus, S. pneumonia, S. gordonii, S. sanguis, S. salivarius, and S. mitis). Similar activity of Example 8 was observed against Candida (data not shown). Other Example barrier-forming compositions exhibited similar PAE against microorganisms.
- Example 7 exhibits greater prolonged antimicrobial activity than comparative Example 70, and that additional amounts of CPC have more than a simple additive effect on anti-microbial activity.
- Example 73 Scanning electron microscopy was also used to show that treatment of S. sanguis, (Example 71), S. oralis, (Example 72), and C. albicans (Example 73) with the composition of Example 3 resulted in destruction of cellular integrity.
- Examples 71-73 cells were grown in the presence of Example 3 for 24 hours. Next, the cells were washed to remove residual formulation, dehydrated by passing through a series of alcohol solutions (10% to 100%, v/v) and processed for SEM analysis. Control Examples 74-76 differed from Examples 71-73 in that they were not grown in the presence of Example 3.
- biofilms are precursors to certain infectious diseases, in Examples 77-79, experiments were performed to determine whether the barrier-forming compositions can prevent formation of biofilms by bacteria and yeasts. Biofilms were formed using an in vitro model. See Chandra et al. "In vitro Growth and Analysis of Candida Biofilms" Nature Protocols 3(12): 1909-1924 (2008).
- Example 3 barrier-forming composition exhibits activity against bacterial and fungal biofilms.
- three different microorganisms C. albicans, S. oralis, and S. salivarius
- PBS, 1 : 1 phosphate buffered saline
- Figure 16 also reports data on Examples 77-79 as a graph of % inhibition versus growth control. These results showed that Example 3 barrier-forming composition inhibited bacterial and fungal microbes with an MIC of 0.2% against biofilms formed by S. salivarius, S. oralis, or C. albicans.
- Example 80 we evaluated the effect of 1 minute exposure of C. albicans early phase biofilms to Example 3, and found that even with an exposure for as short a time as 1 minute, it was able to inhibit biofilm formation (Figure 17).
- Example 81 was an untreated control sample.
- barrier-forming composition To determine whether the barrier-forming composition can treat biofilms, we evaluated its activity against fully formed mature biofilms. Biofilms were grown to mature phase, and then exposed to Example 7 for 2 or 4 hours, and the resulting CFUs were determined. A composition that causes at least 2-log reduction in microbial CFUs compared to untreated cells is considered to be effective against microbial biofilms.
- Example 7 possesses potent activity against biofilms formed by bacteria and fungi.
- the Barrier-Forming Composition is also Active against Viruses
- barrier-forming composition against viruses including respiratory viruses (influenza virus H1 1, strain 2009/Hl l/infA) and the human immunodeficiency virus (HIV) was determined.
- the barrier-forming composition inhibits the infectivity of influenza A
- MDCK Madin Darby canine kidney
- Example 85 cell monolayers were exposed to the Example 7 barrier-forming composition.
- control Example 86 the cell layers were exposed to optiMEM (+P/S,+Lglu) tissue culture media for different times: (1) Tl : 30 min exposure, (2) T2: lh exposure, (3) T3: 2h exposure.
- MOI multiplicity of infection
- TO infected immediately after exposure
- Infected cells were then centrifuged, resuspended in 500 ⁇ of growth medium, and incubated at 32.5 °C for 48 hours.
- FIG. 18 shows the effect of Example 7 on cytopathic effects of influenza-infected MDCK cells (Example 85) (panels A and C), and control Example 86 (panels B and D). Images were obtained from: phase contrast (A-B), and immunofluorescence microscopy (C- D). No identifying cytopathic effect (CPE) was observed in formulation-treated cells.
- Untreated cells displayed typical CPE including focal rounding and degenerative changes.
- Example 85 The data showed that exposure of cell monolayers to Example 7 for 30 minutes, 1 hour, or 2 hours remained confluent and healthy (Example 85). In contrast, in the untreated cells and cells treated immediately prior to infection (TO) (control Example 86) demonstrated substantial cytopathic effect. As seen in Figure 18 panel C, no fluorescence was observed in the barrier-forming composition treated cells of Example 85, while the untreated cells of Example 86 exhibited fluorescence ( Figure 18 panel D).
- Figure 20 shows levels of influenza virus in infected treated cells (Example 87) and untreated cells (Example 88), as determined by quantitative PCR.
- Example 87 cells were treated with Example 7 and in control Example 88 the cells were left untreated. Later the supernatants were collected and analyzed for the presence of virus.
- a reference standard was prepared using a cDNA fragment of the H1N1 matrix gene and human RNAse P amplified by conventional RT-PCR, gel purified (QIAquick, Qiagen, Valencia, CA), and quantified using a spectrophotometer (Beckman Coulter, Brea, CA).
- Example 87 cells treated Example 7 for 30 min or 60 min did not have detectable influenza at 48 hours post infection. Moreover, treatment with Example 7 for 2 hours resulted in a 6-fold decrease in viral load, compared to the untreated control or those treated immediately prior to infection (Example 88). [261] Table VIII
- Barrier-forming composition has direct antiviral effect against influenza virus
- Example 89-91 a standardized amount of influenza (0.1 MOI) was pretreated for 5 minutes at room temperature with: (1) Example 7 (to form Example 89), (2) control Example 6, a compound without CPC but with preservatives (to form Example 90), and (3) control Example 5 placebo alone (a compound without CPC and preservatives) (to form Example 91). After the 5 minute incubation virus/drug mix was diluted by an additional equal volume with optiMEM (+P/S,+Lglu) to dilute out the treatment compositions.
- optiMEM (+P/S,+Lglu
- Example 89-91 CV-1 cells were prepared as described in above. The Example 89-91 treated and untreated viruses were then inoculated onto the cells as described above.
- Influenza viral load was determined by real time PCR as described above.
- the data as shown in Figure 21 showed significant decrease in viral load for influenza virus pretreated with the Example 7 barrier-forming composition containing the antimicrobial agent CPC (Example 89), compared to those containing only the barrier-forming composition and/or preservative but no CPC (Examples 90 and 91).
- Pre-treatment of virus with Example 7 exhibited significant decrease in viral copies, compared to formulations with no CPC.
- Example 7 barrier-forming composition possesses direct antiviral activity against influenza virus that is not inherent in Examples 5 and 6.
- Example 7 the barrier-forming composition's ability to inhibit the infectivity of influenza A (2009/Hl l/infA) was tested. African Green Monkey Kidney (CV-1) cells were grown in 24-well plates to 90% confluence. Next, the barrier-forming composition, Example 7, was applied to the cells (20% Example 7, 80%OptiMeM, working CPC concentration of 0.02 %.) in Example 92. Each time point matched with control Example 93 (No barrier-forming composition applied, 100% OptiMeM). The barrier-forming composition was allowed to dwell on the surface for 30 minutes, and then removed from the ceil monolayer. Cells were thoroughly washed twice with sterile optiMEM (+PfS,+Lglu).
- Infected cells were grown at 32.5°C for 96 hours at 5% CO 2 .
- the influenza viral load was determined by real time PCR.
- Figure IB may be referred to as a possible mechanism accounting for the inhibition of infection.
- Examples 94-96 determined whether the barrier-forming composition possessed activity against HIV.
- Host MT mammalian cells were plated into 96-well round bottom plates at a density of 15,000 cells/well in RPMI/10%FBS/PS. The next day (Day 2), virus was pretreated with control Example 5 (to form Example 94), control Example 6 (to form Example 95), or Example 7 (to form Example 96) for 5 minutes and added to cells. After 24 hours of exposure to formulation, the MT (macaque) mammalian cells were washed 3 times with phosphate buffered saline (PBS) and fresh media was replaced.
- PBS phosphate buffered saline
- FIG. 23 shows a graph of the viral copies per mL for each of Examples 72-74 over a 9 day span.
- Example 7 in Example 96 exhibited anti-HIV activity at all time points monitored post-treatment.
- Example 97 An experiment was performed to determine whether the barrier- forming composition exhibits activity against the common oral Epstein-Barr virus (EBV). Western blotting was used to evaluate the ability of the Example 8 barrier-forming composition to degrade lytic viral protein EAD (indicating inhibition of viral replication).
- EBV Epstein-Barr virus
- Example 97 EBV-infected gastric epithelial cells were exposed to different dilutions (1 : 16, 1 :32 and 1 :64) of Example 8, and the presence of EAD protein was detected using specific antibodies. Presence of cellular ⁇ -actin was used as an indicator of epithelial cell integrity. As shown in Figure 24, 1 :64 dilution of Example 8 degraded EAD without affecting cellular actin. These results demonstrate that Example 8 specifically inhibits viral replication, and as such, is an effective anti-viral and useful for prevention of viral infection.
- Example 98 In control Example 98 an untreated EHOM was tested. In Example 99 S. mitis bacteria was overlaid on the barrier-forming composition as described above.
- Example 100 is a comparative example showing the activity of commercially available LISTERTNE (containing ethanol (26.9%), menthol, thymol, methyl salicylate, and eucalyptol) against X mitis bacteria. Table IX shows the results.
- Example 101-103 the same procedure of Examples 98-100 was performed except Candida albicans fungus was tested on the barrier-forming composition as described above. Table X shows the results.
- Example 103 is comparative, showing the activity of
- Example 7 barrier-forming composition maintained activity for up to and including 24 hours.
- the Example 7 barrier-forming composition continued to maintain an intact barrier on EHOM tissues for up to and including 24 hours.
- Filter inserts of 3 ⁇ and 8 ⁇ diameter pore size were used for testing the passage of bacteria (Streptococcus salivarius) and fungi (Candida albicans), respectively. Glycerin or xanthan gum or their combinations (100 aliquots) were overlaid on the surface of the filter to form a barrier.
- the filter had a diameter of 24 mm.
- the film had a thickness of approximately 0.01 mm on the filter, mimicking a value in the range of thicknesses of the composition film when applied in a therapeutically effective amount to the mouth.
- 5 x 10 4 cells of either bacteria or fungi were applied on top of the formed barrier in the filter inserts.
- Microbial cells retained by the compositions of Examples 104-153 formed on filter inserts were trapped by the barrier, and were viable, thus demonstrating that the formed barrier does not have an inherent antimicrobial property without an antimicrobial agent.
- the microbes retained in the barrier were still active and could pose a threat to infection; for example, if they are freed from the barrier by abrasion or after the barrier loses its integrity.
- an effective barrier may be formed at lower concentrations of glycerine and/or xanthan gum when an effective antimicrobial is added. This is because the antimicrobial and barrier act in tandem to stop and/or kill the harmful microbes.
- Example 154-157 Each EHOM was covered with 300 of one of the tested formulations and left under the sterile hood for 10 minutes at room temperature (25 °C). At the end of the contact period, tissues were washed twice with culture medium to remove the formulations.
- Example 158 After treatment with Examples 3 and 4, the EHOMs were then examined for possible macroscopic tissue damage (presence of holes). Tissue damage was also investigated by histological analyses. For this purpose, biopsies were taken from each EHOM and fixed with 4% paraformaldehyde solution and then embedded in paraffin. Thin sections (4 ⁇ ) were stained with eosin-hematoxilyn and mounted with a coverslip in 50%-glycerine mounting medium, observed through an optical microscope, and photographed. The treated EHOMs and a control untreated EHOM were examined for macroscopic tissue damage and structural changes. There was no visible damage (holes) in the untreated or treated tissues at a magnification of X500 in five different EHOMs tested.
- Example 156 and 157 EHOMs that were treated with the 5% dilution of Examples 3-7 of the barrier-forming composition were then over-layered with 1 x 10 6 cells of either C. albicans or S. mutans in a volume of 100 ⁇ .
- the EHOMs were then placed on air-liquid culture plates and incubated for 24 hours in 5% C0 2 humid atmosphere at 37°C. Following this incubation period, aliquots of the culture supernatant were collected and subjected to a Lactate dehydrogenase (LDH) cytotoxicity assay (Promega, Madison, WI, USA), as per the manufacturer instructions. 50 ⁇ of each supernatant were transferred to a sterile 96-well flat-bottom plate.
- LDH Lactate dehydrogenase
- Wound repair assays were performed. Briefly, oral (gingival) epithelial cells (lxlO 4 ) and fibroblasts (lxlO 3 ) were seeded into wells of 6-well plates and grown in appropriate culture medium. Upon confluency, wounds were made in the confluent monolayer of each well using a 200 ⁇ , pipette tip. Cultures were then exposed to 1 and 5% by weight dilutions of Examples 3 and 4 for about 2 minutes.
- Figure 26 shows representative photographs of a wounded oral epithelial cell culture treated with Example 3 (5% dilution) for 10 minutes, immediately after the wound (panel A), after about 6 hours (panel D), and after about 24 hours (panel E).
- Panels B and C show an equivalent wound on an untreated control confluent culture of oral epithelial cells after about 6 hours and about 24 hours, respectively. Similar results were seen for the cell culture treated with Example 4.
- Glycerine-Xanthan Gum Formulations Form a Coating on the Human Oral Mucosa
- Example 7 formulation with Gentian Violet (GV) as a marker dye.
- the spiked product 750 ⁇ was sprayed onto the oral cavity of human volunteers. Post-application, the oral cavity was inspected for staining, and the images were captured using a digital camera. As shown in Figure 27, the formulation stained both cheeks and the dorsal/ventral surface of the tongue.
- Example 162 S. mutans microbial cells were exposed to Example 7 for one minute, washed to remove any residual agent, and allowed to grow in a petri-dish containing fresh growth medium. Growth of organisms at 37 °C was monitored for a 6 hour period, and photomicrographs were taken every 20 minutes over the 6 hour incubation period using a camera connected to the microscope.
- Example 7 The duration of activity of Example 7 was determined in healthy individuals by evaluating the effect of a single application on microbial burden of the oral cavity.
- three healthy individuals (over 18 years of age, healthy mouth) were enrolled with informed consent, and asked to apply a single application of the composition of Example 7 on their cheeks.
- a single application was defined as three sprays of 0.25 ml each in volume.
- swabs were collected from these individuals at baseline (pre-treatment), 1 hour, 2 hours, and 6 hours post-treatment. Swabs were cultured on agar media plates specific for aerobic or anaerobic organisms, incubated for 24-28 hours at 37 °C, and the number of CFUs were counted. Effect of Example 7 on microbial burden was determined (CFUs), and percentage inhibition was calculated for each post-exposure time point relative to the baseline (0 minutes) CFUs.
- Example 7 led to consistent reduction in microbial load for up to 6 hours (See Figure 29A, which shows CFUs of a representative tested individual. Treatment with the barrier-forming composition resulted in 69% to 96% reduction of the microbial burden in the oral cavity (See Figure 29B, which shows a representative individual's reduction in microbial load.)
- Example 167-169 The activity of the barrier-forming composition over a 5-day period against oral microbes was evaluated.
- three healthy individuals were enrolled, and asked to apply a single dosage (three sprays 0.75 mLs total) of Example 7 three times daily (approximately 9 AM, noon, and 3 PM) for a 5 -day period (representing a typical 5 -day work- week).
- Swabs were collected from these individuals at baseline (before application on day 1) and at the end of the day on each day during the 5-day period. Collected swabs were cultured on agar media plates, incubated for 24-28 hours at 37 °C and at 5% CO 2 humidity, and the number of CFUs were counted.
- Example 7 barrier-forming composition The effect of the Example 7 barrier-forming composition on microbial burden was determined (as median CFUs for the three subjects), and percentage inhibition was calculated for each post-exposure time point relative to the baseline (0 min) CFUs.
- Figure 30 shows these results in a graph of CFUs versus time (Figure 3 OA) and reduction in microbial load versus time ( Figure 30B).
- Examples 167-169 demonstrate that application of Example 7 over 5 days led to consistent reduction in microbial load over the 5-day test period ( Figure 3 OA).
- Treatment with the Example 7 barrier-forming composition resulted in 65% -88% reduction of the median microbial burden in the oral cavity of the study participants (Figure 30B).
- One group used the example barrier-forming composition every two hours, three times a day, for five days (a typical work week).
- the other group used the example barrier- forming composition every two hours, four times a day, for five days (a typical work week). No substantial difference was noted in the two groups.
- Swabs were collected on days 1, 2, 3, and 5 at the end of the day (8 hours after the first administration of the barrier-forming composition) and cultured on media specific for aerobic and anaerobic bacteria. Data were presented as number of microbes: total, aerobic and anaerobic.
- Figure 31 shows a graph of total microbial load and breaks down the total into aerobic and anaerobic counts from just prior to treatment and on day 5 of treatment.
- Figure 32 shows graphs of microbial load over the 5 day period in oral samples obtained from three representative study participants.
- the in vivo testing showed that the barrier-forming composition exhibits antimicrobial activity against oral microbes, as measured by reduction in the levels of these organisms, over both short- and long-term duration.
- Example 199 an in vitro filter insert-based model (see Figure 33) was used to test different humectants at different concentrations.
- compositions were prepared according to Table XII based on the mixing procedures used for Examples 3-8.
- Example 199-205 were placed into filter inserts (pore size 0.8 ⁇ diameter, that allows both bacteria and fungi to pass through) and allowed to form a layer.
- organisms were overlaid on the layer formed by the test solutions.
- the filter inserts containing the layer of test solutions and microorganisms were then placed on the surface of agar media plates and incubated for 24 hours at 37 °C. After the incubation period, the agar media plates were evaluated for growth on filter insert and in the agar media. Growth on filter insert but no growth in agar media indicated that the test solution formed a barrier, which prevented the microbes from passing through. In contrast, microbial growth in the filter insert as well as the agar media indicated that no such barrier was formed.
- Example 214 the formulation of Example 7 was made, except the neutral agent Citral was used instead of CPC.
- the assay described above in Examples 48-61 was used to perform these studies.
- Example 215 thin layer chromatography analysis was used to compare the hydrophobicity of Example 7 with a hydrophobic composition.
- the hydrophobic composition was comprised of the components in Table XIV.
- Example 7 10 ⁇ of Example 7 and the hydrophobic composition were deposited on pre-made TLC plates (at a distance of 2 cm from the bottom edge). The spots were air-dried for 5 minutes, and the plates were placed in a TLC chromatography jar containing water as a solvent. The TLC system was allowed to run until the solvent front reached the top edge of the plate. Plates were removed and the solvent and sample fronts were marked. The Relative Front (Rf) values were calculated for the two samples using the formula II:
- Example 7 did not exhibit any mobility in the aqueous solvent, demonstrating that this formulation is hydrophobic or not hydrophilic.
- a barrier-forming composition was made by mixing the components according to Table XV below in water to form a solution.
- a eucalyptol component was also included in an amount of 5X per the Homeopathic Pharmacopeia, but also did not affect the test results, other than demonstrating that the composition still works with this component added into it. All percentages are by weight.
- the barrier-forming composition was also shown to have effectiveness in killing allergy causing molds. MIC tests were performed on a polystyrene plastic surface.
- Example 217 the barrier-forming composition of Example 216 was tested to determine its MIC against Stachybotrys MRL 9740.
- the Example 7 composition had an MIC of 0.06 micrograms/ml.
- Example 218 the barrier-forming composition of Example 216 was tested to determine its MIC against Aspergillus fumigatus 18748.
- the Example 7 composition had an MIC of 0.49 micrograms/ml.
- Example 219 the barrier-forming composition of Example 216 was tested to determine its MIC against Cladosporium.
- the Example 7 composition had an MIC of 0.39 micrograms/ml.
- Examples 219-224 [368] In Examples 219-224 the effect of barrier-forming composition on MRSA biofilm formation on a silicone elastomer disc surface was evaluated.
- Example 219-221 three silicone elastomer discs with a 1 cm diameter were pre- sprayed with .25 mL with the Example 7 barrier-forming composition for 60 min and incubated at 37 °C.
- Example 222-224 a control example was performed by treating a silicone elastomer disc with an equivalent amount of a phosphate -buffered saline (PBS) for 60 minutes and incubated at 37 °C.
- PBS phosphate -buffered saline
- Example 219-224 pretreated discs were each submerged in 4 mL MRSA suspension (l x lO 7 cells/mL), and incubated at 37 °C for 90 min ("Adhesion Phase"). Next, the discs with adherent cells were removed and transferred to wells containing 4 mL of Brain Heart Infusion (BHI). The wells were incubated at 37 °C on a rocker for 24 hours. Biofilm formation on the discs was evaluated by quantitative culturing on BHI agar plates. Scanned images of the wells were recorded using a scanner.
- BHI Brain Heart Infusion
- FIG. 34 shows images of colony burden in biofilms formed by MRSA on the PBS treated (A, C, E) and Example 7 treated (B, D, F) discs.
- Example 7 barrier-forming composition was tested to determine its efficacy against several strains of Bordetella pertussis.
- test Examples 225-235 agar-based assays were constructed in which Example 7 barrier-forming compositoin was incorporated in Regan-Lowe Charcoal agar BBL #297883 plates as a 64 microgram/mL dilution in water.
- Control Examples 236-246 were agar plates containing no Example 7 barrier-forming composition.
- 5x10 4 cells (50 uL) of Bordetella pertussis were spotted on the test surface and plates were incubated at 37 degrees C for 24 hours.
- Table XVII confluent growth was observed in control Examples 236 to 246, while no growth was observed in test Examples 236-246.
- the designation 4+ means luxurious growth.
- Example 7 The antiviral activity of the barrier-forming composition, Example 7 (in various diluted concentrations) was evaluated against the ATCC VR-1200 strain of rhinovirus.
- Example 7 composition was applied to cell monolayers at varying concentrations (5%, 10%, 15%, 20%, 50% diluted in 400 microliter optiMEM (+P/S, +Lglu)) for a working CPC concentration of 0.005%, 0.01%, 0.015%, 0.02% and 0.05% respectively, and was allowed to dwell for 1 hour prior to inoculation.
- 400 microliter optiMEM (+P/S,+Lglu) was applied to the cells and allowed to dwell for 1 hour prior to inoculation.
- the cell monolayers were then removed from the Example 7 dilutions or control optiMEM and rhinovirus was applied at a multiplicity of infection (MOI) of 0.1.
- MOI multiplicity of infection
- Cells were incubated with virus at 32.5°C for 1 hour. After which the inoculum was removed and 500ul OptiMEM +P/S +Lglu was placed on the cells. Cells were then grown at 32.5°C at 5% C02. After 5 days incubation, cell culture supernatants were collected for rhinovirus viral load quantification.
- Example 247-251 cell culture supernatants were measured by real time PCR.
- Example 252 significantly decreased rhinovirus viral load was demonstrated in Example 251, which was a 50% concentration of Example 7.
- Examples 253 and 254 [384] A test Example 253 was formulated with a 50% Example 7 diluted suspension (0.05 CPC concentration) in 500 microliter optiMEM (+P/S,+Lglu). A control Example 254 was formulated as a control solution with no Example 7 (500 microliter optiMEM (+P/S,+Lglu)). Examples 253 and 254 were applied the cells disclosed in Examples 246-252, but at defined intervals: T-l hour, T-30 min, and T-0 (Immediate) prior to infection.
- the cell monolayers were then removed from the Example 253 suspension and the Example 254 control solution.
- the rhinovirus viral particles were applied to the treated cell monolayers at a multiplicity of infection (MOI) of 0.1.
- MOI multiplicity of infection
- Cells were incubated with virus at 32.5°C for 1 hour. After which the inoculum was removed and 500ul OptiMEM +P/S +Lglu was placed on the cells.
- Cells were then grown at 32.5°C at 5% CO 2 for 5 days.
- the cells treated with Example 253 and 254 were viewed daily for the presence of cytopathic effect. After 5 days incubation, cell culture supernatant was gathered for immunofluorescence and rhinovirus viral load quantification.
- Figure 35 discloses photos of cells treated with test Example 253 at Figure 35(a) T - l hr, Figure 35(c) T - 30 min and Figure 35(b) T 0 (immediate). None of these photos demonstrated any cytopathic effect and healthy cells overgrew the plate. However, as shown in Figure 35(d) the Example 254 untreated control cells demonstrated focal rounding, detachment and cell death. Cytopathic effect determination included the development of focal rounding, cell size enlargement or reduction, syncytial formation, development of multinucleated giant cells, and detachment.
- Immunofluorescence was determined as follows: Virus infected cell monolayers and uninfected control were washed with sterile PBS. The cells were trypsinized, spotted upon wells on slides and fixed with acetone. The slides were tested by DFA employing FITC labeled monoclonal antibodies. An indirect immunofluorescence assay was performed using Light Diagnostics Pan-Enterovirus Detection Kit (Millipore). This detection kit is well described for having cross reactivity with rhinovirus infected cells. All antibody dwell steps occurred for 1 hour at 37°C. Following a final wash, cells were evaluated at a wavelength of 488 nm for the presence of fluorescence.
- Figure 36 discloses immunofluorescence photos of cells pretreated treated with test Example 253 at Fig. 36(d) T - lhr, Fig. 36(b) T - 30min and Fig. 36(c) T-0 (immediate). The cells treated with Example 253 for 1 hour and 30 minutes displayed no
- Viral load for the samples was quantified as follows: Cell culture supernatants were collected and stored at -80°C. Nucleic acid was extracted using QIAamp Viral RNA Kit (QIAGEN, Valencia, CA). Random hexamer primers (Invitrogen Carlsbad, CA) were used to create a cDNA library for each specimen. Reverse transcription reactions were performed with M-MLV RT (Invitrogen, Carlsbad, CA) according to the manufacturer's specifications. Quantitative analysis was performed on a StepOne Plus Taqman Real Time PCR (Applied Biosystems, Branchburg, NJ ) using TaqMan Universal PCR Master Mix (Applied
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015506981A JP2015514758A (ja) | 2012-04-17 | 2013-01-04 | 長時間持続性表面抗菌剤及び塗布方法 |
EP13777625.8A EP2838570A4 (en) | 2012-04-17 | 2013-01-04 | PERMANENT ANTIMICROBIAL SURFACE AND METHOD OF USE |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
USPCT/US12/33921 | 2012-04-17 | ||
PCT/US2012/033921 WO2012145307A1 (en) | 2011-04-19 | 2012-04-17 | Method of inhibiting harmful microorganisms and barrier-forming composition therefor |
US201261725375P | 2012-11-12 | 2012-11-12 | |
US61/725,375 | 2012-11-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013158165A1 true WO2013158165A1 (en) | 2013-10-24 |
Family
ID=49383904
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2013/020254 WO2013158165A1 (en) | 2012-04-17 | 2013-01-04 | Long-lasting surface anti-microbial and method of application |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP2838570A4 (enrdf_load_stackoverflow) |
JP (1) | JP2015514758A (enrdf_load_stackoverflow) |
WO (1) | WO2013158165A1 (enrdf_load_stackoverflow) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10426761B2 (en) | 2011-04-19 | 2019-10-01 | Arms Pharmaceutical, Llc | Method for treatment of disease caused or aggravated by microorganisms or relieving symptoms thereof |
WO2023123421A1 (zh) * | 2021-12-31 | 2023-07-06 | 振德医疗用品股份有限公司 | 一种长效抗菌消毒剂及制备方法和应用 |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2012245665B2 (en) | 2011-04-19 | 2017-06-15 | Arms Pharmaceutical Llc. | Method of inhibiting harmful microorganisms and barrier-forming composition therefor |
EP3407639A4 (en) | 2016-01-18 | 2019-07-17 | SoftBank Corp. | BASISSTATION DEVICE AND COMMUNICATION SYSTEM |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3993777A (en) * | 1975-08-12 | 1976-11-23 | Bio-Lab, Inc. | Aqueous compositions to aid in the prevention of bovine mastitis |
WO1999059410A1 (en) * | 1998-05-21 | 1999-11-25 | Troy Technology Corporation, Inc. | Stabilized antimicrobial compositions containing halopropynyl compounds |
WO2000027191A1 (en) * | 1998-11-09 | 2000-05-18 | The Procter & Gamble Company | Disposable premoistened wipe containing an antimicrobial protease inhibitor |
WO2007016067A2 (en) * | 2005-07-29 | 2007-02-08 | Delaval, Inc. | Antibacterial composition and method of use |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4666708A (en) * | 1984-01-27 | 1987-05-19 | Oral Research Laboratories, Inc. | Dental rinse |
KR20010013377A (ko) * | 1997-06-04 | 2001-02-26 | 데이비드 엠 모이어 | 마일드한 잔류성 항균 조성물 |
ATE225392T1 (de) * | 1997-07-29 | 2002-10-15 | Alcon Lab Inc | Konditionierungslösungen für die pflege von harten kontaktlinsen |
US6749869B1 (en) * | 1997-09-26 | 2004-06-15 | Ecolab | Acidic aqueous chlorite teat dip providing shelf life, sanitizing capacity and tissue protection |
US6663902B1 (en) * | 2000-09-19 | 2003-12-16 | Ecolab Inc. | Method and composition for the generation of chlorine dioxide using Iodo-Compounds, and methods of use |
US20070166244A1 (en) * | 2006-01-19 | 2007-07-19 | The Procter & Gamble Company | Compositions comprising silicone pressure sensitive adhesives for delivering oral care substances |
MX2008015189A (es) * | 2006-05-31 | 2009-03-06 | Dial Corp | Composiciones antimicrobianas que contienen alcohol que tienen eficiencia mejorada. |
US8568697B2 (en) * | 2008-03-21 | 2013-10-29 | Colgate-Palmolive Company | High fluoride ion recovery compositions |
AU2012245665B2 (en) * | 2011-04-19 | 2017-06-15 | Arms Pharmaceutical Llc. | Method of inhibiting harmful microorganisms and barrier-forming composition therefor |
-
2013
- 2013-01-04 WO PCT/US2013/020254 patent/WO2013158165A1/en active Application Filing
- 2013-01-04 JP JP2015506981A patent/JP2015514758A/ja active Pending
- 2013-01-04 EP EP13777625.8A patent/EP2838570A4/en not_active Withdrawn
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3993777A (en) * | 1975-08-12 | 1976-11-23 | Bio-Lab, Inc. | Aqueous compositions to aid in the prevention of bovine mastitis |
WO1999059410A1 (en) * | 1998-05-21 | 1999-11-25 | Troy Technology Corporation, Inc. | Stabilized antimicrobial compositions containing halopropynyl compounds |
WO2000027191A1 (en) * | 1998-11-09 | 2000-05-18 | The Procter & Gamble Company | Disposable premoistened wipe containing an antimicrobial protease inhibitor |
WO2007016067A2 (en) * | 2005-07-29 | 2007-02-08 | Delaval, Inc. | Antibacterial composition and method of use |
Non-Patent Citations (1)
Title |
---|
See also references of EP2838570A4 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10426761B2 (en) | 2011-04-19 | 2019-10-01 | Arms Pharmaceutical, Llc | Method for treatment of disease caused or aggravated by microorganisms or relieving symptoms thereof |
WO2023123421A1 (zh) * | 2021-12-31 | 2023-07-06 | 振德医疗用品股份有限公司 | 一种长效抗菌消毒剂及制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
JP2015514758A (ja) | 2015-05-21 |
EP2838570A1 (en) | 2015-02-25 |
EP2838570A4 (en) | 2016-03-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20150031729A1 (en) | Low-tack surface anti-microbial coating composition and method of application | |
US20130123308A1 (en) | Long-lasting surface anti-microbial and method of application | |
US20190358149A1 (en) | Method of inhibiting harmful microorganisms and barrier-forming composition therefor | |
KR102108109B1 (ko) | 국소 소독 제제 및 이의 용도 | |
US20200093811A1 (en) | Method for treatment of disease caused or aggravated by microorganisms or relieving symptoms thereof | |
US20130123309A1 (en) | Method for reducing microbial load for individuals with elevated risk conditions | |
WO2013158165A1 (en) | Long-lasting surface anti-microbial and method of application | |
WO2014074331A1 (en) | Low-tack surface anti-microbial coating composition and method of application | |
JP6901824B2 (ja) | 微生物により引き起こされる若しくは悪化する疾患の治療方法、又はその症状の緩和方法 | |
WO2014107572A1 (en) | Body surface treatment composition and method | |
US20130039959A1 (en) | Method of inhibiting hiv and barrier-forming composition therefor | |
US20150306042A1 (en) | Body surface treatment composition and method | |
US20230301884A1 (en) | Antiseptic compositions | |
US20230050626A1 (en) | Bladder, ureter, kidney, urethra, prostate and catheter anti-microbial, and biofilm prevention, reduction and treatment | |
US12280018B2 (en) | Antiseptic compositions | |
US20240041852A1 (en) | Method for treatment of disease caused or aggravated by microorganisms or relieving symptoms thereof | |
EP2941248A1 (en) | Body surface treatment composition and method |
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: 13777625 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2015506981 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REEP | Request for entry into the european phase |
Ref document number: 2013777625 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2013777625 Country of ref document: EP |