NO752938L - - Google Patents
Info
- Publication number
- NO752938L NO752938L NO752938A NO752938A NO752938L NO 752938 L NO752938 L NO 752938L NO 752938 A NO752938 A NO 752938A NO 752938 A NO752938 A NO 752938A NO 752938 L NO752938 L NO 752938L
- Authority
- NO
- Norway
- Prior art keywords
- silanated
- antimicrobial
- compound
- phenol
- compound according
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 54
- 230000000845 anti-microbial effect Effects 0.000 claims description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 48
- ACGUYXCXAPNIKK-UHFFFAOYSA-N hexachlorophene Chemical compound OC1=C(Cl)C=C(Cl)C(Cl)=C1CC1=C(O)C(Cl)=CC(Cl)=C1Cl ACGUYXCXAPNIKK-UHFFFAOYSA-N 0.000 claims description 34
- 229960004068 hexachlorophene Drugs 0.000 claims description 33
- 150000002989 phenols Chemical class 0.000 claims description 27
- 239000004599 antimicrobial Substances 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 19
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 claims description 19
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 14
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 12
- -1 methoxy, ethoxy Chemical group 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 8
- 239000000376 reactant Substances 0.000 claims description 8
- 229910000077 silane Inorganic materials 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000005907 alkyl ester group Chemical group 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 2
- 239000012429 reaction media Substances 0.000 claims 2
- VXHYVVAUHMGCEX-UHFFFAOYSA-N 2-(2-hydroxyphenoxy)phenol Chemical compound OC1=CC=CC=C1OC1=CC=CC=C1O VXHYVVAUHMGCEX-UHFFFAOYSA-N 0.000 claims 1
- 150000005166 2-hydroxybenzoic acids Chemical class 0.000 claims 1
- 150000005168 4-hydroxybenzoic acids Chemical class 0.000 claims 1
- 239000005711 Benzoic acid Substances 0.000 claims 1
- 235000010233 benzoic acid Nutrition 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 28
- 239000003208 petroleum Substances 0.000 description 22
- 238000012360 testing method Methods 0.000 description 17
- 239000011521 glass Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 11
- 244000005700 microbiome Species 0.000 description 11
- 229910052710 silicon Inorganic materials 0.000 description 11
- NCKMMSIFQUPKCK-UHFFFAOYSA-N 2-benzyl-4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1CC1=CC=CC=C1 NCKMMSIFQUPKCK-UHFFFAOYSA-N 0.000 description 10
- RIKCMEDSBFQFAL-UHFFFAOYSA-N octyl 4-hydroxybenzoate Chemical compound CCCCCCCCOC(=O)C1=CC=C(O)C=C1 RIKCMEDSBFQFAL-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- MDNWOSOZYLHTCG-UHFFFAOYSA-N Dichlorophen Chemical compound OC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1O MDNWOSOZYLHTCG-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229960003887 dichlorophen Drugs 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000010703 silicon Substances 0.000 description 9
- WFJIVOKAWHGMBH-UHFFFAOYSA-N 4-hexylbenzene-1,3-diol Chemical compound CCCCCCC1=CC=C(O)C=C1O WFJIVOKAWHGMBH-UHFFFAOYSA-N 0.000 description 8
- ZTJORNVITHUQJA-UHFFFAOYSA-N Heptyl p-hydroxybenzoate Chemical compound CCCCCCCOC(=O)C1=CC=C(O)C=C1 ZTJORNVITHUQJA-UHFFFAOYSA-N 0.000 description 8
- 239000004284 Heptyl p-hydroxybenzoate Substances 0.000 description 8
- 235000019251 heptyl p-hydroxybenzoate Nutrition 0.000 description 8
- 229960003258 hexylresorcinol Drugs 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 150000003141 primary amines Chemical class 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000011109 contamination Methods 0.000 description 6
- 150000001412 amines Chemical group 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 5
- 230000000813 microbial effect Effects 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 229960004889 salicylic acid Drugs 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012736 aqueous medium Substances 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 239000000919 ceramic Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 241000195493 Cryptophyta Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000002070 germicidal effect Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 229910052572 stoneware Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VHBSECWYEFJRNV-UHFFFAOYSA-N 2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1O.OC(=O)C1=CC=CC=C1O VHBSECWYEFJRNV-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi 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
- 239000005909 Kieselgur Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 239000006087 Silane Coupling Agent Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000008275 binding mechanism Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- SVHOVVJFOWGYJO-UHFFFAOYSA-N pentabromophenol Chemical compound OC1=C(Br)C(Br)=C(Br)C(Br)=C1Br SVHOVVJFOWGYJO-UHFFFAOYSA-N 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229910052573 porcelain Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 150000003870 salicylic acids Chemical class 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical compound [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- KVSKGMLNBAPGKH-UHFFFAOYSA-N tribromosalicylanilide Chemical compound OC1=C(Br)C=C(Br)C=C1C(=O)NC1=CC=C(Br)C=C1 KVSKGMLNBAPGKH-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
Silanerte fenoliske forbindelserSilanated phenolic compounds
Foreliggende oppfinnelse angår nye silanerte fenoliske forbindelser/en fremgangsmåte for fremstilling derav og deres anvendelse for å skaffe substratoverflater med antimikrobiell beskyttelse. The present invention relates to new silanated phenolic compounds/a method for their production and their use for providing substrate surfaces with antimicrobial protection.
Ved fremstilling, håndtering og pakking av materialer som farmaceutica, matvarer og drikkevarer, er mikrobiell forurensning et vesentlig problem, da lagringsholdbarheten og anvendbarheten av slike produkter påvirkes direkte av slike forurensninger. Det er derfor vesentlig at pakkeapparatur og beholdere er .i en steril eller nesten steril tilstand for å dorhindre eller nedsette innslutningen av uønskede mikrober i de pakkede produkter. Dessuten er der ved fremstilling og ser-vering av mat, som i restauranter, hoteller og andre institusjoner, et problem med mikrobiell forurensning da matvarene håndteres, gjøres istand og serveres. I hospitaler og lignende institusjoner må områder som vegger etc. også holdes i en så mikroorganisme-f ri tils tand .som mulig . Tidligere har germi-cider og desinfeksjonsmidler vært anvendt for å rengjøre slike områder, apparater og beholdere som anvendes for pakning av matvarer og drikkevarer, og for å rengjøre slike spisesaker som tallerkener, kopper, glass og lignende som også kan være utsatt for uønsket mikrobeforurensning. In the manufacture, handling and packaging of materials such as pharmaceuticals, foodstuffs and beverages, microbial contamination is a significant problem, as the shelf life and usability of such products are directly affected by such contamination. It is therefore essential that packaging equipment and containers are in a sterile or nearly sterile condition in order to prevent or reduce the inclusion of unwanted microbes in the packaged products. Furthermore, in the production and serving of food, such as in restaurants, hotels and other institutions, there is a problem with microbial contamination when the food is handled, prepared and served. In hospitals and similar institutions, areas such as walls etc. must also be kept as micro-organism-free as possible. In the past, germicides and disinfectants have been used to clean such areas, devices and containers used for packaging food and beverages, and to clean such eatables as plates, cups, glasses and the like which may also be exposed to unwanted microbial contamination.
Der er dessuten også problemet med å forhindre eller nedsette veksten av slike mikrober i det fyllte og forseglede, pakkede produkt. Dette problem er blitt overvunnet tidligere ved å inkludere antimikrobielle midler eller lignende i selve produktet. Det antimikrobielle middel må imidlertid nødvendig-vis påføres, inntaes eller brukes på annen måte, sammen med produktet som det beskytter, og et slikt system later noe til bake å ønske. Således angir f.eks. US patent nr. 3 730 701 anvendelsen av visse silyl-kvartære aminer for å bekjempe alger i vandige medier. De silyl-kvartære aminer tilsettes til det vandige medium/og blandt andre ulemper betyr dette at en ytterligere mengde middel må anvendes hår systemet opp-fylles etc. Et lignende silylamin er angitt i US patent nr. There is also the problem of preventing or reducing the growth of such microbes in the filled and sealed packaged product. This problem has been overcome in the past by including antimicrobial agents or the like in the product itself. However, the antimicrobial agent must necessarily be applied, ingested or otherwise used together with the product it protects, and such a system leaves something to be desired. Thus, e.g. US Patent No. 3,730,701 discloses the use of certain silyl quaternary amines to control algae in aqueous media. The silyl-quaternary amines are added to the aqueous medium/and, among other disadvantages, this means that a further amount of agent must be used when the system is filled up, etc. A similar silylamine is specified in US patent no.
3 719.697 og dette er angitt å være nyttig som overflateaktivt 3,719,697 and this is stated to be useful as a surfactant
middel, baktericid og fungicid. Forsøk på å overvinne disse ulemper er angitt i US patent nr. 3 817 739 som lærer å be-handle filtermediet for akvarier etc. med de kvartære ammonium-forbindelser for å bekjempe algedannelse. agent, bactericide and fungicide. Attempts to overcome these disadvantages are indicated in US patent no. 3 817 739 which teaches to treat the filter medium for aquariums etc. with the quaternary ammonium compounds to combat algae formation.
Det har nu vist seg, og dette danner grunnlaget for foreliggende oppfinnelse, at en ny gruppe av siliconforbindel-ser som har antimikrobielle egenskaper, er istand til å hefte ved en rekke substratoverflater innbefattende kiselsyreholdige materialer, som flasker, stentøy, keramikk og polymere materialer, og derved beskytte disse overflater mot forurensning av mikrober. It has now been shown, and this forms the basis of the present invention, that a new group of silicone compounds which have antimicrobial properties are capable of adhering to a number of substrate surfaces including silicic acid-containing materials, such as bottles, stoneware, ceramics and polymeric materials, and thereby protect these surfaces against contamination by microbes.
Det har dessuten vist seg at beskyttelsen som med-deles det behandlede substrat strekker seg over et relativt langt tidsrom, og endog motstår gjentatte vaskinger av det behandlede substrat. It has also been shown that the protection imparted to the treated substrate extends over a relatively long period of time, and even resists repeated washings of the treated substrate.
Foreliggende oppfinnelse fremskaffer nye silanerte forbindelser erholdt ved å omsette en forbindelse med formelen: The present invention provides new silanated compounds obtained by reacting a compound with the formula:
hvor R er methoxy, ethoxy eller propoxy, where R is methoxy, ethoxy or propoxy,
X er hydrogen eller amino-lavere alkyl med 1-4 carbonatomer, og X is hydrogen or amino-lower alkyl with 1-4 carbon atoms, and
n er 2, 3 eller 4,n is 2, 3 or 4,
med en antimikrobiell fenolisk forbindelse.with an antimicrobial phenolic compound.
Fortrinnsvis er X hydrogen, og silanreaktanten har den generelle formel: Preferably, X is hydrogen and the silane reactant has the general formula:
hvor R og n er som ovenfor angitt. where R and n are as stated above.
Av forbindelsene med.formel Ia som er særlig viktige, er y-aminopropyl-triethoxy-silan og produkter erholdt ved om setning derav utgjør en foretrukken utførelsesform av oppfinnelsen. Of the compounds with formula Ia which are particularly important, γ-aminopropyl-triethoxy-silane and products obtained by synthesis thereof constitute a preferred embodiment of the invention.
En lang rekke fenoliske forbindelser kan anvendes, idet betingelsen er at forbindelsene må ha antimikrobielle egenskaper. Eksempler'på slike fenoliske forbindelser er de mange klorerte og bromerte fenoler. A wide range of phenolic compounds can be used, the condition being that the compounds must have antimicrobial properties. Examples of such phenolic compounds are the many chlorinated and brominated phenols.
Av de mulige antimikrobielt aktive fenoliske forbindelser foretrekkes de som er valgt blandt klorerte fenoler, Of the possible antimicrobially active phenolic compounds, those chosen from chlorinated phenols are preferred,
-bis-fenoler eller -difenyletherej en med klor eller alkyl med 6-9 carbonatomer substituert toverdig fenol; en ortho- eller para-hydroxybenzoesyre eller en alkylester derav med 1-12 -bis-phenols or -diphenyl ethers with chlorine or alkyl with 6-9 carbon atoms substituted divalent phenol; an ortho- or para-hydroxybenzoic acid or an alkyl ester thereof with 1-12
carbonatomer.carbon atoms.
Uttrykkene "klorerte", "bromerte", "klor", og "brom" i ovenstående definisjoner refererer seg til produkter inneholdende én eller flere halogensubstituenter. The terms "chlorinated", "brominated", "chloro", and "bromo" in the above definitions refer to products containing one or more halogen substituents.
De nye forbindelser antaes å ha den generelle formel: The new compounds are assumed to have the general formula:
hvor R-^ og R2hver er methoxy, ethoxy eller propoxy; wherein R 1 and R 2 are each methoxy, ethoxy or propoxy;
X er hydrogen eller amino-lavere alkyl med 1-4 carbonatomer, men fortrinnsvis hydrogen; X is hydrogen or amino-lower alkyl of 1-4 carbon atoms, but preferably hydrogen;
n er 2, 3 eller 4; ogn is 2, 3 or 4; and
Ra er resten av en antimikrobiell fenolisk forbindelse, fortrinnsvis én av de like ovenfor angitte. Ra is the residue of an antimicrobial phenolic compound, preferably one of those indicated just above.
Foretrukne forbindelser ifølge oppfinnelsen er de med den generelle formel: Preferred compounds according to the invention are those with the general formula:
hvor RC_ l er som ovenfor angitt. where RC_ l is as stated above.
Disse forbindelser kan erholdes ved omsetning av y-aminopropyl-triethoxysilan med den tilsvarende fenoliske forbindelse. These compounds can be obtained by reacting γ-aminopropyl-triethoxysilane with the corresponding phenolic compound.
Av særlig interesse er forbindelsene med den generelle formel III hvor R Cl er resten fra hexaklorofen, penta-kl<p>rofen og 2,4 ,4 1-trifklor-21-hydroxyfenol.' Disse forbindelser antaes å ha følgende formel: Of particular interest are the compounds of the general formula III where R Cl is the residue from hexachlorophene, pentachlorophene and 2,4,4 1-trichloro-21-hydroxyphenol. These compounds are believed to have the following formula:
(a) Silanerte hexaklorofen(a) Silanated hexachlorophene
(b) Silanert 2, 4, 4'- triklor- 2'- hydroxy- fenylether (c) Silanert pentaklorfenol (b) Silanated 2, 4, 4'- trichloro- 2'- hydroxy- phenyl ether (c) Silanated pentachlorophenol
Andre bemerkelsesverdige antimikrobielle fenoliske grupper representert ved Ra er de som er avledet av følgende antimikrobielle fenoliske forbindelser: diklorofen; Other notable antimicrobial phenolic groups represented by Ra are those derived from the following antimicrobial phenolic compounds: dichlorophen;
o-be.nzyl-p-klbrf enol; o-benzyl-p-klbrf enol;
pentabromfenol og tribromsalicylanilid; pentabromophenol and tribromosalicylanilide;
ortho- eller para-hydroxybenzoater med 1-12 carbonatomer i alkylkjeden, fortrinnsvis heptyl- og octylesterne; salicylsyrer; og ortho- or para-hydroxybenzoates with 1-12 carbon atoms in the alkyl chain, preferably the heptyl and octyl esters; salicylic acids; and
hexylresorcinolhexylresorcinol
Således bindes den antimikrobielle fenoliske forbindelse, som hexaklorofen, til siliciumatomet over oxygenet av Thus, the antimicrobial phenolic compound, such as hexachlorophene, is bound to the silicon atom above the oxygen of
(en) hydroxylgruppe under dannelse av den ønskede antimikrobielle forbindelse og (ethyl) alkohol-biprodukt. Forbindelsene ifølge oppfinnelsen kan være faste stoffer eller væsker, idet smeltepunktet eller kokepunktet vanligvis er 50° C eller mere eller mindre enn det for den fenoliske utgangsforbindelse som vil bli vist i det følgende. (a) hydroxyl group to form the desired antimicrobial compound and (ethyl) alcohol by-product. The compounds according to the invention can be solids or liquids, the melting point or boiling point being usually 50° C or more or less than that of the starting phenolic compound which will be shown in the following.
De antimikrobielle forbindelser med den generelle formel II fremstilles ved en ny fremgangsmåte som involverer å omsette silaneringsmidlet med formelen: The antimicrobial compounds of the general formula II are prepared by a new process which involves reacting the silanating agent with the formula:
X-NH(CH2)nSi(R)3IX-NH(CH2)nSi(R)3I
hvor hver R er methoxy, ethoxy eller propoxy; wherein each R is methoxy, ethoxy or propoxy;
X er hydrogen eller amino-lavere alkyl med 1-4 carbonatomer; og X is hydrogen or amino-lower alkyl of 1-4 carbon atoms; and
n er 2, 3 eller 4n is 2, 3 or 4
med den fenoliske forbindelse med antimikrobielle egenskaper. with the phenolic compound with antimicrobial properties.
Den generelle reaksjon ved foreliggende oppfinnelse kan derfor skrives som følger: The general reaction of the present invention can therefore be written as follows:
hvor Ra, R, R-^, R2/X og n er som ovenfor angitt. where Ra, R, R-^, R2/X and n are as indicated above.
De foretrukne reaktanter med formel I er de hvor X er hydrogen. En foretrukken utførelsesform av fremgangsmåten ifølge oppfinnelsen kan derfor skrives: The preferred reactants of formula I are those where X is hydrogen. A preferred embodiment of the method according to the invention can therefore be written:
hvor Ra, R, R-j.'R2 og n er som ovenf°r angitt, og særlig hvor. alle gruppene R er ethoxy og n er 3. where Ra, R, R-j, R2 and n are as stated above, and in particular where. all groups R are ethoxy and n is 3.
Et bekvemt silaneringsmiddel er y-aminopropyl-triethoxysilan og de foretrukne fenoliske reaktanter er hexaklorofen, diklorofen, o-benzyl-p-klorfenol, pentaklorfenol, heptyl-p-hydroxybenzoat, octyl-p-hydroxybertzoat, salicylsyre, 2,4,4'-triklor-2'-hydroxyfenylether og hexyl-resorcinol. Av disse er de mest foretrukne som reaktanter hexaklorofen, 2 ,4,4'-triklor-2'-hydroxyfenylether og pentaklorfenol. A convenient silanizing agent is γ-aminopropyl-triethoxysilane and the preferred phenolic reactants are hexachlorophene, dichlorophene, o-benzyl-p-chlorophenol, pentachlorophenol, heptyl-p-hydroxybenzoate, octyl-p-hydroxybertzoate, salicylic acid, 2,4,4'- trichloro-2'-hydroxyphenyl ether and hexyl resorcinol. Of these, the most preferred as reactants are hexachlorophene, 2,4,4'-trichloro-2'-hydroxyphenyl ether and pentachlorophenol.
Spesifike utførelsesformer innbefatter for eksempel (a) den foretrukne generelle reaksjon med enkle fenoler som følger: Specific embodiments include, for example, (a) the preferred general reaction with simple phenols as follows:
hvor R, R-^og R2er methoxy, ethoxy eller propoxy; where R, R 1 and R 2 are methoxy, ethoxy or propoxy;
Y er for eksempel når a er vanligvis 1, -COOH, OH, alkyl t benzyl, amid som anilid, estergrupper (som -COOC2H5 og Y is for example when a is usually 1, -COOH, OH, alkyl t benzyl, amide such as anilide, ester groups (such as -COOC2H5 and
-COOC^H^) og når a er mere enn 1, for eksempel 5, brom eller særlig klor ; og -COOC^H^) and when a is more than 1, for example 5, bromine or especially chlorine; and
n er 2, 3 eller 4,n is 2, 3 or 4,
(b) Reaksjonen med det foretrukne y-aminopropyl-triethoxy-silan som silaneringsforbindelse og hexaklorofen som den antimikrobielle reaktant: (b) The reaction with the preferred γ-aminopropyl-triethoxy-silane as the silanizing compound and hexachlorophene as the antimicrobial reactant:
Reaksjonen utføres fortrinnsvis i et organisk oppløs-ningsm-iddel hvori både silanet og de antimikrobielle fenoliske forbindelser er oppløselige, for eksempel kloroform. Reaksjons-blandingen kokes i alminnelighet under tilbakeløp inntil reaksjonen er i det vesentlige fullstendig og den ønskede silanerte antimikrobielle forbindelse isoleres, vanligvis ved vasking med petrolether og/eller vann. The reaction is preferably carried out in an organic solvent in which both the silane and the antimicrobial phenolic compounds are soluble, for example chloroform. The reaction mixture is generally refluxed until the reaction is substantially complete and the desired silanated antimicrobial compound is isolated, usually by washing with petroleum ether and/or water.
Som nevnt ovenfor gir de nye forbindelser ifølge oppfinnelsen overflater med antimikrobielle egenskaper ved å adhere eller bindes til slike overflater. Skjønt den. nøyaktige mekanisme ved hvilken forbindelsene ifølge oppfinnelsen festes til de forskjellige substrater ikke er helt kjent, antaes det at én eller annen form for kjemisk binding er involvert. Uttrykkene adhere eller adhesjon som anvendt i beskrivelsen, innbefatter slike typer av binding. I ethvert tilfelle likegyl-dig hvilken bindingsmekanisme er involvert, har de nye forbindelser de fordelaktige anvendelsesområder som her er angitt. As mentioned above, the new compounds according to the invention provide surfaces with antimicrobial properties by adhering or binding to such surfaces. Although it. exact mechanism by which the compounds according to the invention attach to the various substrates is not completely known, it is assumed that one or the other form of chemical bonding is involved. The terms adhere or adhesion as used in the description include such types of bonding. In any case, regardless of which binding mechanism is involved, the new compounds have the advantageous areas of application indicated here.
Som det fremgår av eksemplene nedenfor er en rekke antimikrobielle forbindelser blitt silanert ved omsetning med det foretrukne silaneringsmiddel y-aminopropyl-triethoxysilan under dannelse av silanerte derivater som i det vesentlige bibeholder de antimikrobielle egenskaper av den opprinnelige antimikrobielle forbindelse mens de samtidig er istand til å bindes til glass, siliciumholdige eller andre overflater. As can be seen from the examples below, a number of antimicrobial compounds have been silanized by reaction with the preferred silanizing agent γ-aminopropyl-triethoxysilane to form silanated derivatives which essentially retain the antimicrobial properties of the original antimicrobial compound while at the same time being able to bind to glass, silicon-containing or other surfaces.
En eksempelvis og foretrukken reaksjon av hexaklorofen med y-aminopropyl-triethoxysilanet fører til et silanert hexaklorofenderivat som dannes ved avspaltning av ethylalkohol fra silanforbindelsen og binding av silicium over oxygenet av en hydroxylgruppe i hexaklorofen. Reaksjonen synes å være riktig for silaneringen av de antimikrobielle forbindelser angitt her. An exemplary and preferred reaction of hexachlorophene with the y-aminopropyl-triethoxysilane leads to a silanated hexachlorophene derivative which is formed by cleavage of ethyl alcohol from the silane compound and bonding of silicon over the oxygen of a hydroxyl group in hexachlorophene. The reaction appears to be correct for the silanation of the antimicrobial compounds reported here.
Hypotesen for reaksjonen ble bekreftet ved å prøve reaksjonsproduktet på primært amin (fluoresc.aminmetoden) hvor prøven var positiv. Massespektroskopi og kjernemagnetisk resonansspektrografiske undersøkelser ble også utført og disse prøver indikerer at det silanerte hexaklorofen er bundet over oxygenet av en hydroxylgruppe til siliciumet i det silanerte amin som vist i ovenstående formel for silanert hexaklorofen. Infrarødt spektrum og analyse på silicium viser nærvær av silicium i reaksjonsproduktet i en mengde som stemmer overens med ovenstående formel. The hypothesis for the reaction was confirmed by testing the reaction product on primary amine (fluoresc.amine method) where the sample was positive. Mass spectroscopy and nuclear magnetic resonance spectrographic investigations were also carried out and these tests indicate that the silanated hexachlorophene is bound over the oxygen of a hydroxyl group to the silicon in the silanated amine as shown in the above formula for silanated hexachlorophene. Infrared spectrum and analysis of silicon shows the presence of silicon in the reaction product in an amount that agrees with the above formula.
Det silanerte hexaklorofen har en molekylvekt på 579 og oppviser utmerkede antimikrobielle egenskaper. Silangruppen av forbindelsen gir sterk binding for det monomolekylære belegg på overflater. The silanated hexachlorophene has a molecular weight of 579 and exhibits excellent antimicrobial properties. The silane group of the compound provides strong bonding for the monomolecular coating on surfaces.
Den samme reaksjon som angitt ovenfor for silanering av hexaklorofen, har også vært anvendt for å fremstille silanert diklorofen, o-benzyl-p-klorfenol, pentaklorfenol, heptyl-p-hydroxybenzoat, octyl-p-hydroxybenzoat, salicylsyre, 2,4,4'-triklor-2'-hydroxyfenylether og hexyl-resorcinol. The same reaction as indicated above for the silanation of hexachlorophene has also been used to prepare silanated dichlorophene, o-benzyl-p-chlorophenol, pentachlorophenol, heptyl-p-hydroxybenzoate, octyl-p-hydroxybenzoate, salicylic acid, 2,4,4 '-trichloro-2'-hydroxyphenyl ether and hexyl-resorcinol.
De ovenstående forbindelser er blitt silanert med y-aminopropyl-triethoxysilan og det er sluttet at reaksjonen angitt for hexaklorofen ovenfor er generell for slike forbindelser. Alle forbindelsene bibeholder utmerkede antimikrobielle egenskaper og bindingsegenskaper til en rekke substrater. The above compounds have been silanized with γ-aminopropyl-triethoxysilane and it is concluded that the reaction indicated for hexachlorophene above is general for such compounds. All compounds retain excellent antimicrobial properties and binding properties to a variety of substrates.
Silangruppen er forenet over oxygen av en hydroxylgruppe av den antimikrobielle utgangsforbindelse. Bibeholdel-sen av vesentlig antimikrobiell virkning av de silanerte forbindelser ifølge oppfinnelsen er uventet, da hydroxylgruppen av fenoliske og andre slike antimikrobielle forbindelser har vært betraktet som vesentlig for antimikrobiell aktivitet. The silane group is joined over oxygen by a hydroxyl group of the parent antimicrobial compound. The retention of significant antimicrobial action of the silanated compounds according to the invention is unexpected, as the hydroxyl group of phenolic and other such antimicrobial compounds has been considered essential for antimicrobial activity.
I tilfelle av de silanerte derivater hvor den antimikrobiell utgangsforbindelse har bare én hydroxylgruppe, er det endog mere uventet, da hydrogenet av hydroxylgruppen er erstattet med silangruppen. In the case of the silanated derivatives where the antimicrobial starting compound has only one hydroxyl group, it is even more unexpected, as the hydrogen of the hydroxyl group is replaced by the silane group.
Den foretrukne reaksjon omfatter å blande den antimikrobielle forbindelse med y-aminopropyl-triethoxysilan vanligvis i et oppløsningsmiddel for begge forbindelser, fortrinnsvis i kloroform. Aminet, trimethylamih, ble opprinnelig antatt å gi en katalytisk virkning i reaksjonen, men senere arbeider tyder på at triethylaminet antagelig ikke er nødvendig. Blandingen kokes under tilbakeløp i ca. 75 - 90 minutter og nær slutten av tilbakeløpskokningen kokes ca. 50 % eller mere av kloroformen av. Oppløsningen (eller suspensjonen) tillates å avkjøle til værelsetemperatur og ca. 4 - 5 volum pétrolether (k.p. 40 - 60° C) tilsettes under god blanding. På dette tidspunkt felles i alminnelighet forbindelsene med høye smeltepunkter (over ca. 60° C og vanligvis 120° C og høyere) (ofte som amorfe masser) etter silaneringen ved tilsetning av pétrolether. Etter henstand over natten ved værelsetemperatur blir de silanerte derivater med høyere smeltepunkter krystallinske. The preferred reaction involves mixing the antimicrobial compound with γ-aminopropyl-triethoxysilane usually in a solvent for both compounds, preferably in chloroform. The amine, trimethylamih, was originally thought to provide a catalytic effect in the reaction, but later work suggests that the triethylamine is probably not necessary. The mixture is boiled under reflux for approx. 75 - 90 minutes and near the end of the reflux boil approx. 50% or more of the chloroform of. The solution (or suspension) is allowed to cool to room temperature and approx. 4 - 5 volumes of petroleum ether (b.p. 40 - 60° C) are added while mixing well. At this point, the compounds with high melting points (above approx. 60° C and usually 120° C and higher) generally separate (often as amorphous masses) after the silanation by the addition of petroleum ether. After standing overnight at room temperature, the silanated derivatives with higher melting points become crystalline.
Morluten helles på av og krystallene vaskes flere ganger med ca. fire volum pétrolether. Til slutt suspenderes krystallene i to volumpétrolether og males godt med en morter og pestill for å vaske ut forurensninger. Krystallene fjernes så fra morluten ved sentrifugering eller filtrering og vaskes igjen flere ganger med ca. fire volum pétrolether, filtreres og lufttørres. Det silanerte antimikrobielle preparat erholdt, ved denne fremgangsmåte er rent, med et skarpt smeltepunkt og godt infrarødt spektrum. Vanligvis har de silanerte forbindelser smeltepunkter som er i det vesentlige lavere enn det for den opprinnelige forbindelse med 50° C eller mere. Med de antimikrobielle reaktantpreparater som har lavere smeltepunkter (100° C eller lavere) har det vist seg at felning med petrol- éther ikke ga krystallinsk materiale, men vanligvis gummiaktige masser. Diklorofen, når det silaneres ved ovenstående fremgangsmåte, ga et derivat med et smeltepunkt på 48° C og forbindelsen ble uvegerlig gummiaktig ved henstand. Diklorofen selv har et smeltepunkt på 163° C. The mother liquor is poured on and the crystals are washed several times with approx. four volumes of petroleum ether. Finally, the crystals are suspended in two volumes of petroleum ether and ground well with a mortar and pestle to wash out impurities. The crystals are then removed from the mother liquor by centrifugation or filtration and washed again several times with approx. four volumes of petroleum ether, filtered and air-dried. The silanated antimicrobial preparation obtained by this method is pure, with a sharp melting point and good infrared spectrum. Generally, the silanated compounds have melting points substantially lower than that of the parent compound by 50°C or more. With the antimicrobial reactant preparations having lower melting points (100° C or lower) it has been found that precipitation with petroleum ether did not give crystalline material, but usually gummy masses. Dichlorophene, when silanized by the above method, gave a derivative with a melting point of 48° C. and the compound invariably became gummy on standing. Dichlorophene itself has a melting point of 163°C.
Det har vist seg at disse gummiaktige bunnfall var uoppløselige i vann, men kunne vaskes utstrakt med vann for å fjerne forurensninger slik overskuddet av silan-koblingsmiddel og triethylamin. Det vaskede residuum er oppløselig i methanol og analyse av methanoloppløsningene viste lett nærværet av den silanerte forbindelse. De følgende eksempler belyser frem- It was found that these gummy precipitates were insoluble in water, but could be washed extensively with water to remove contaminants such as excess silane coupling agent and triethylamine. The washed residue is soluble in methanol and analysis of the methanol solutions readily showed the presence of the silanated compound. The following examples highlight
gangsmåtene ifølge oppfinnelsen.the methods according to the invention.
Eksempel 1Example 1
Silanert hexaklorofenSilanated hexachlorophene
10 g hexaklorofen anbringes i en 100 ml tohalset rundkolbe. Til kolben tilsettes 75 ml kloroform, 3,3 ml triethylamin og 7 ml y-aminopropyl-triethoxysilan. Noen få kokeskår ble også tilsatt. Blandingen ble kokt under tilbakeløp (63 - 69° C) i 75 minutter. Etter avkjøling ble innholdet av kolben overført til en 500 ml korket glassbeholder og 300 ml pétrolether (kokepunkt 40 - 60° C) ble tilsatt, og fikk henstå i kjøleskap over natten for krystallisasjon. Den påfølgende dag ble den overstående væske heldt av og krystallene igjen suspendert i 200 ml pétrolether, blandet godt, tillatt å sette seg og den overstående væske ble heldt av. Derpå bie krystallene suspendert i ca. 50 ml pétrolether, malt godt i en morter og pistill, tilsatt 150 ml pétrolether og fikk igjen felles. Place 10 g of hexachlorophene in a 100 ml two-necked round flask. 75 ml of chloroform, 3.3 ml of triethylamine and 7 ml of γ-aminopropyl-triethoxysilane are added to the flask. A few cooking chips were also added. The mixture was refluxed (63-69°C) for 75 minutes. After cooling, the contents of the flask were transferred to a 500 ml corked glass container and 300 ml of petroleum ether (boiling point 40 - 60° C) was added and allowed to stand in a refrigerator overnight for crystallization. The following day the supernatant was decanted and the crystals resuspended in 200 ml of petroleum ether, mixed well, allowed to settle and the supernatant decanted. The crystals are then suspended for approx. 50 ml of petroleum ether, ground well in a mortar and pestle, added 150 ml of petroleum ether and combined again.
Den klare overstående væske ble heldt av. Vasking med 150 ml pétrolether ble gjentatt ytterligere tre ganger. Etter den siste vask ble krystallene filtrert på et filtrerpapir og fikk lufttørre. Utbyttet var 14,0 g (96,6 % av det teoretiske), sm.p. 110 - 111° C. Krystallene var kremfarvet. Infrarødt spektrum viste nærvær av siliciumholdig gruppe. Analyse på primært amin var positiv. The clear supernatant liquid was decanted. Washing with 150 ml of petroleum ether was repeated a further three times. After the last wash, the crystals were filtered on a filter paper and allowed to air dry. The yield was 14.0 g (96.6% of the theoretical), m.p. 110 - 111° C. The crystals were cream colored. Infrared spectrum showed the presence of silicon-containing group. Analysis for primary amine was positive.
Eksempel 2Example 2
Silanert diklorofenSilanated dichlorophene
2 g diklorofen tilsettes til 25 ml kloroform i en 2-halset pæreformet kolbe. Til blandingen tilsettes 2 ml y-NH2(CH2)3Si(OC2Hg)3og 1 ml triethylamin og noen få kokeskår. Blandingen går fullstendig i oppløsning og kokes under tilbake-løp i 60 minutter. Etter tilbakeløpskokning avdampes ca. 50 % av kloroformen. Derpå avkjøles oppløsningen og 75 ml pétrolether tilsettes hvorved man får et gummiaktig bunnfall etter henstand i kjøleskap over natten. Den overstående væske helles av og 20 mi frisk pétrolether tilsettes under god blanding. 2 g of dichlorophene are added to 25 ml of chloroform in a 2-necked pear-shaped flask. 2 ml of γ-NH2(CH2)3Si(OC2Hg)3 and 1 ml of triethylamine and a few boiling chips are added to the mixture. The mixture dissolves completely and is boiled under reflux for 60 minutes. After refluxing, evaporate approx. 50% of the chloroform. The solution is then cooled and 75 ml of petroleum ether is added, whereby a gummy precipitate is obtained after standing in a refrigerator overnight. The excess liquid is poured off and 20 ml of fresh petroleum ether is added while mixing well.
Et ferskt bunnfall dannes. Bunnfallet tillates å sette seg og den klare overstående væske helles av. 20 ml friskt pétrolether tilsettes og igjen etter avsetning av bunnfallet fjernes den overstående væske. Denne operasjon gjentas ytterligere tre ganger inntil bunnfallet forandres fra en gummi til en hård, knusbar masse. Sistnevnte males til et pulver, filtreres og lufttørres. Utbytte er 1,7 g (ca. 50 % av det teoretiske) av et kremhvitt pulver med et smeltepunkt på 48° C. Det infra-røde spektrum viser nærværet av en silicium-holdig gruppe. Pulveret er tilbøyelig til å bli gummiaktig ved henstand over natten i en lukket ampulle i en eksikator. Dette ble iakttatt på tre forskjellige preparater. A fresh precipitate forms. The precipitate is allowed to settle and the clear supernatant liquid is poured off. 20 ml of fresh petroleum ether is added and again after depositing the precipitate, the excess liquid is removed. This operation is repeated a further three times until the precipitate changes from a rubber to a hard, crushable mass. The latter is ground into a powder, filtered and air-dried. The yield is 1.7 g (about 50% of the theoretical) of a creamy white powder with a melting point of 48° C. The infrared spectrum shows the presence of a silicon-containing group. The powder tends to become gummy on standing overnight in a closed ampoule in a desiccator. This was observed on three different preparations.
Eksempel 3Example 3
Silanert heptyl- p- hydroxybenzoatSilanated heptyl-p-hydroxybenzoate
2 g heptyl-p-hydroxybenzoat tilsettes til 25 ml kloroform i en to-halset pæreformet kolbe. Derpå tilsettes 1 ml triethylamin og 2 ml y-aminopropyl-triethoxysilan og innholdet av kolben blandes inntil heptyl-p-hydroxybenzoatet oppløses. Noen få kokeskår tilsettes og blandingen kokes under tilbakeløp i 1 time, idet det meste av kloroformen kokes av. Et uopplø-selig residuum erholdes. (Anm.: Dette residuum gir en gummiaktig masse som motstår alle forsøk på krystallisasjon ved behandling med pétrolether som beskrevet for diklorofen-syntese). Derpå tilsettes 30 ml vann til residuet og blandes godt. med en rørestav i flere minutter. Det tillates å avsette seg og det vandige skik± fraskilles. Gjenta vaskingen med 30 ml vann ytterligere fire ganger for fullstendig å fjerne eventuelt uomsatt triethylamin/Y-aminopropyl-triethoxysilan og andre forurensninger. Et renset residuum på ca. 2 - 3 g silanert heptyl-p-hydroxybenzoat fåes. Dette oppløses fullstendig i 10 ml methanol hvorved man får en 15 til 20 %-ig oppløsning som passende kan fortynnes med methanol for anvendelse for behandlingsformål. Forsøk indikerer at materialet i oppløsningen er hydrofobt og gir en positiv reaksjon på primære aminer. Disse forsøk indikerer reaksjon.mellom heptyl-p-hydroxybenzoatet og silan-koblingsreagenset. Fremgangsmåten angitt i denne syntese er et alternativ for den som anvendes for å silanere hexaklorofen og er anvendbar på silanerte fenoler som ikke kan krystalliseres ved behandling med pétrolether. 2 g of heptyl-p-hydroxybenzoate are added to 25 ml of chloroform in a two-necked pear-shaped flask. 1 ml of triethylamine and 2 ml of γ-aminopropyl-triethoxysilane are then added and the contents of the flask are mixed until the heptyl-p-hydroxybenzoate dissolves. A few boiling shards are added and the mixture is refluxed for 1 hour, most of the chloroform being boiled off. An insoluble residue is obtained. (Note: This residue gives a gummy mass which resists all attempts at crystallization when treated with petroleum ether as described for dichlorophen synthesis). Then add 30 ml of water to the residue and mix well. with a stirring rod for several minutes. It is allowed to settle and the aqueous phase is separated. Repeat the washing with 30 ml of water four more times to completely remove any unreacted triethylamine/Y-aminopropyl-triethoxysilane and other contaminants. A purified residue of approx. 2 - 3 g of silanated heptyl-p-hydroxybenzoate are obtained. This is completely dissolved in 10 ml of methanol whereby a 15 to 20% solution is obtained which can be suitably diluted with methanol for use for treatment purposes. Tests indicate that the material in the solution is hydrophobic and gives a positive reaction to primary amines. These tests indicate reaction between the heptyl-p-hydroxybenzoate and the silane coupling reagent. The procedure indicated in this synthesis is an alternative to that used to silanize hexachlorophene and is applicable to silanized phenols that cannot be crystallized by treatment with petroleum ether.
Eksempel 4Example 4
Silanert o- benzyl- p- klorfenol ( BCP) 2 g o-benzyl-p-klorfenol tilsettes til 25 ml kloroform i en tohalset pæreformet kolbe. Derpå tilsettes 1 ml triethylamin og 2 ml y-aminopropyl-triethoxysilan og blandes inntil BCP er fullstendig oppløst og kolbe-innholdet kokes så under til-bakeløp i 1 time. Etter tilbakeløpskokning avkokes det meste av kloroformen. Et gråbrunt viskøst flytende residuum fåes i et volum på. 2 - 3 ml. Dette vaskes ved blanding med en glass-stav med 30 ml vann i flere minutter. Etter avsetning helles det vandige toppsjikt av, og vaskingen med 30 ml vann gjentaes ytterligere tre ganger. Det uoppløselige residuum oppløses i 10 ml alkohol hvorved man får en blek gul 15 - 20 %-ig oppløs-ning av silanert o-benzyl-p-klorfenol. Prøver på denne oppløs-ning viser at innholdet er hydrofobt mens den opprinnelige o-benzyl-p-klorfenol er dette. Dessuten fåes en positiv indika-sjon på primære aminer. Begge prøver er bevis på silaneringen av BCP. Silanated o-benzyl-p-chlorophenol (BCP) 2 g of o-benzyl-p-chlorophenol are added to 25 ml of chloroform in a two-necked pear-shaped flask. 1 ml of triethylamine and 2 ml of γ-aminopropyl-triethoxysilane are then added and mixed until the BCP is completely dissolved and the contents of the flask are then boiled under reflux for 1 hour. After refluxing, most of the chloroform boils off. A grey-brown viscous liquid residue is obtained in a volume of 2 - 3 ml. This is washed by mixing with a glass rod with 30 ml of water for several minutes. After settling, the aqueous top layer is poured off, and the washing with 30 ml of water is repeated a further three times. The insoluble residue is dissolved in 10 ml of alcohol, whereby a pale yellow 15-20% solution of silanated o-benzyl-p-chlorophenol is obtained. Tests on this solution show that the content is hydrophobic, while the original o-benzyl-p-chlorophenol is this. A positive indication of primary amines is also obtained. Both samples are evidence of the silanation of BCP.
Eksempel 5Example 5
Silanert pentaklorfenol ( PCP)Silanated pentachlorophenol (PCP)
2 g pentaklorfenol tilsettes til 25 ml kloroform i en tohalset pæreformet kolbe. Til innholdet tilsettes så 1 ml triethylamin og 2. ml y-aminopropyl-triethoxysilan og blandet inntil PCP er oppløst. Derpå kokes oppløsningen under tilbake-løp i. 1 time og det meste a<y>kloroformen kokes av. Derpå tilsettes tre volum pétrolether (k.p. 40 - 60° C) til residuet, det blandes godt med en rørestav og hensettes over natten ved værelsetemperatur. Et hvitt krystallinsk bunnfall dannes. Den overstående væske helles av og bunnfallet vaskes med 30 ml pétrolether og etter avsetning helles den overstående væske av. Bunnfallet vaskes ytterligere tre ganger med 30 ml pétrolether hver gang. Etter fjernelse av den siste overstående væske lufttørres så bunnfallet. Et kremhvitt pulver som veier 3,2 g og har et smeltepunkt på 121° C erholdes. Analyse av pulveret viser nærvær av silicium ved infrarødt spektrum, et primært amin og hydrofobisitet hvilket bekrefter silanering av penta-klorf enol . 2 g of pentachlorophenol are added to 25 ml of chloroform in a two-necked pear-shaped flask. 1 ml of triethylamine and 2 ml of γ-aminopropyl-triethoxysilane are then added to the contents and mixed until the PCP is dissolved. The solution is then boiled under reflux for 1 hour and most of the chloroform is boiled off. Three volumes of petroleum ether (b.p. 40 - 60° C) are then added to the residue, it is mixed well with a stirring rod and left overnight at room temperature. A white crystalline precipitate forms. The overlying liquid is poured off and the precipitate is washed with 30 ml of petroleum ether and, after settling, the overlying liquid is poured off. The precipitate is washed a further three times with 30 ml of petroleum ether each time. After removing the last remaining liquid, the precipitate is then air-dried. A creamy white powder weighing 3.2 g and having a melting point of 121° C is obtained. Analysis of the powder shows the presence of silicon by infrared spectrum, a primary amine and hydrophobicity which confirms the silanation of penta-chlorophenol.
Eksempel 6Example 6
Silanert 2, 4, 4'- triklor- 2'- hydroxydifenylether ( THDP)Silanated 2, 4, 4'- trichloro- 2'- hydroxydiphenyl ether (THDP)
2,5 g THDP (solgt av Ciba^Geigy som "Irgasan DP 300") ble tilsatt til 25 ml kloroform. Derpå ble 1 ml triethylamin og 2 ml vaminopropyl-triethoxysilan tilsatt til kloroformopp-løsningen og blandingen (en klar oppløsning) ble kokt under'tilbakeløp i 1 time. Etter tilbakeløpskokning ble det meste av kloroformen kokt av, etterlatende 3 ml av en klar gul viskøs væske. Denne væske ble så vasket med 40 ml vann under anvendelse av en rørestav. Etter adskillelse av sjiktene ble den overstående væske fraskilt og residuet ble vasket med 40 ml vann. Dette ble gjentatt ytterligere fire ganger for fullstendig å fjerne forurensninger og gjenværende triethylamin og Y-aminopropyl-triethoxysilan. Residuet ble oppløst i 10 ml methanol hvilket ga en 15 - 20 %-ig oppløsning av silanert THDP. Prøver på denne oppløsning bekreftet dannelsen av det silanerte derivat. Det ble iakttatt at ved henstand over natten i kjøleskap dannet der seg to sjikt i methanoloppløsningen. Den høye kon-sentrasjon av det silanerte THDP syntes å bevirke dette da en mere fortynnet oppløsning forble uforandret. 2.5 g of THDP (sold by Ciba^Geigy as "Irgasan DP 300") was added to 25 ml of chloroform. Then 1 ml of triethylamine and 2 ml of vaminopropyltriethoxysilane were added to the chloroform solution and the mixture (a clear solution) was refluxed for 1 hour. After refluxing, most of the chloroform was boiled off, leaving 3 mL of a clear yellow viscous liquid. This liquid was then washed with 40 ml of water using a stirring rod. After separation of the layers, the supernatant liquid was separated and the residue was washed with 40 ml of water. This was repeated four more times to completely remove contaminants and residual triethylamine and Y-aminopropyl-triethoxysilane. The residue was dissolved in 10 ml of methanol, which gave a 15 - 20% solution of silanated THDP. Tests on this solution confirmed the formation of the silanated derivative. It was observed that when left overnight in a refrigerator, two layers formed in the methanol solution. The high concentration of the silanated THDP appeared to cause this as a more dilute solution remained unchanged.
( ■ (■
Eksempel 7Example 7
Silanert salicylsyreSilanated salicylic acid
2 g salicylsyre ble blandet i og oppløst i 25 ml kloroform. Til oppløsningen ble tilsatt 1 ml triethylamin og 2 ml Y-aminopropyl-triethoxysilan og oppløsningen ble kokt under tilbakeløp i 75 minutter. Mot slutten av tilbakeløpskok- ' ningen ble det meste av kloroformen kokt av. Residuet ble vasket åtte ganger med 40 ml pétrolether (k.p. 40 - 55° C) for å fjerne uomsatt materiale. Residuet ble så oppløst i 25 ml methanol hvorved man fikk en gul oppløsning. Denne oppløsning viste ved omsetning med glass positiv hydrofobisitetprøve og en positiv prøve på primære aminer. Disse prøver er tegn på silanering av salicylsyre. 2 g of salicylic acid was mixed in and dissolved in 25 ml of chloroform. To the solution was added 1 ml of triethylamine and 2 ml of Y-aminopropyl-triethoxysilane and the solution was refluxed for 75 minutes. Towards the end of the reflux, most of the chloroform was boiled off. The residue was washed eight times with 40 ml of petroleum ether (b.p. 40 - 55° C) to remove unreacted material. The residue was then dissolved in 25 ml of methanol, whereby a yellow solution was obtained. This resolution by reaction with glass showed a positive hydrophobicity test and a positive test for primary amines. These samples are indicative of silanation of salicylic acid.
Eksempel 8Example 8
Silanert octyl- p- hydroxybenzoatSilanated octyl-p-hydroxybenzoate
2 g octyl-p-hydroxybenzoat ble tilsatt til 25 ml kloroform og blandet godt; Til oppløsningen ble tilsatt 1 ml triethylamin og 2 ml Y-aminopropyl-triethoxysilan og oppløsnin-gen ble kokt under tilbakeløp i 60 minutter. Mot slutten av tilbakeløpskokningen ble det meste av kloroformen kokt av. Residuet ble vasket omhyggelig med god blanding med 5 x 40 ml vann. Når residuet ble oppløst i 10 ml methanol fikk man en 14 ml oppløsning inneholdende ca. 2,5 g silanert oxyl-p-hydroxy-behzoat. Prøver med denne oppløsning etter omsetning med glass ga en positiv hydrofobisitetsreaksjon og oppløsningen ga også en sterk positiv primær aminreaksjon. Begge disse prøver viser silanering av octyl-p-hydroxybenzoat. 2 g of octyl-p-hydroxybenzoate was added to 25 ml of chloroform and mixed well; 1 ml of triethylamine and 2 ml of Y-aminopropyl-triethoxysilane were added to the solution and the solution was refluxed for 60 minutes. At the end of the reflux most of the chloroform was boiled off. The residue was washed thoroughly with good mixing with 5 x 40 ml of water. When the residue was dissolved in 10 ml of methanol, a 14 ml solution containing approx. 2.5 g of silanated oxyl-p-hydroxy-behzoate. Samples with this solution after reaction with glass gave a positive hydrophobicity reaction and the solution also gave a strong positive primary amine reaction. Both of these samples show silanation of octyl-p-hydroxybenzoate.
Eksempel 9Example 9
Silanert hexylresorcinolSilanated hexylresorcinol
2 g hexylresorcinol ble tilsatt til 25 ml kloroform og blandet godt. Til oppløsningen ble tilsatt 1 ml triethylamin og 2 ml Y-aminopropyl-triethoxysilan og oppløsningen ble kokt under tilbakeløp i 60 minutter. MOt slutten av tilbake-løpskokningen ble det meste av kloroformen kokt av. Residuet ble vasket omhyggelig med 5 x 40 ml vann. Etter den siste vasking med det røde, vinfarvede residuum oppløst i 10 ml methanol hvilket ga 15 ml av en oppløsning inneholdende ca. 2,5 g silanert hexylresorcinol. Prøver på dette materiale på glass indikerte en høy grad av hydrofobisitet. Dessuten ga oppløs-ningen en høy positiv prøve på primære aminer. Begge disse prøver viser dannelsen av silanert hexylresor cinol. 2 g of hexylresorcinol was added to 25 ml of chloroform and mixed well. To the solution was added 1 ml of triethylamine and 2 ml of Y-aminopropyl-triethoxysilane and the solution was refluxed for 60 minutes. Towards the end of the reflux, most of the chloroform was boiled off. The residue was washed thoroughly with 5 x 40 ml of water. After the last washing with the red, wine-coloured residue dissolved in 10 ml of methanol which gave 15 ml of a solution containing approx. 2.5 g of silanated hexylresorcinol. Tests of this material on glass indicated a high degree of hydrophobicity. Moreover, the solution gave a high positive sample for primary amines. Both of these samples show the formation of silanated hexylresorcinol.
Formlene for de ovenstående antimikrobielle forbindelser silanert med y-aminopropyl-triethoxysilan antas å være: The formulas for the above antimicrobial compounds silanated with γ-aminopropyl-triethoxysilane are believed to be:
1. Silanert hexaklorofen1. Silanated hexachlorophene
2. Silanert 2,4,4'-triklor-2'-hydroxyfenylether (THDP) 3. Silanert diklorofen 4 . Silanert pentaklorfenol 5. Silanert p-hydroxybenzoesyre 6. Silanert ethyl-p-hydroxybenzoat 7. Silanert heptyl-p-hydroxybenzoat 8. Silanert octyl-p-hydroxybenzoat 9. Silanert O-benzyl-p-klorfenol, 10. Silanert hexylresorcinol 11. Silanert salicylsyre-o-hydroxybenzoesyre 2. Silanated 2,4,4'-trichloro-2'-hydroxyphenyl ether (THDP) 3. Silanated dichlorophene 4 . Silanated pentachlorophenol 5. Silanated p-hydroxybenzoic acid 6. Silanated ethyl-p-hydroxybenzoate 7. Silanated heptyl-p-hydroxybenzoate 8. Silanated octyl-p-hydroxybenzoate 9. Silanated O-benzyl-p-chlorophenol, 10. Silanated hexylresorcinol 11. Silanated salicylic acid-o-hydroxybenzoic acid
Smeltepunktene for de opprinnelige antimikrobielle forbindelser er sammenlignet med smeltepunktene for de sila-i The melting points of the original antimicrobial compounds are compared with the melting points of the sila-i
nerte derivater i tabell A.nert derivatives in Table A.
Eksempel 10 Example 10
Hexaklorofen ble også silanert med y-(3_aminoethyl)-aminopropyl-trimethoxysilan som følger. 3,5 g hexaklorofen ble forenet med 2 ml y-(3~aminoethyl)-aminopropyl-trimethoxysilan i 25 ml kloroform. Blandingen ble kokt under tilbakeløp i ca. 1 time for å koke av det meste av kloroformen. 50 ml pétrolether ble så tilsatt og den dannede gummiaktige masse ble vasket som i de ovenstående eksempler. Det menes at hexakloro-fenet ble forenet med silangruppen over oxygenet av én av hydroxylgruppene, under erstatning av eh ,methoxygruppe på siliciumatomet. Hexachlorophene was also silanized with γ-(3-aminoethyl)-aminopropyl-trimethoxysilane as follows. 3.5 g of hexachlorophene was combined with 2 ml of γ-(3-aminoethyl)-aminopropyl-trimethoxysilane in 25 ml of chloroform. The mixture was boiled under reflux for approx. 1 hour to boil off most of the chloroform. 50 ml of petroleum ether was then added and the gummy mass formed was washed as in the above examples. It is believed that the hexachlorophene was united with the silane group above the oxygen of one of the hydroxyl groups, replacing the eh,methoxy group on the silicon atom.
Vedheftningen av silanert hexaklorofen utført i hen-hold til eksempel 1 ovenfor ble prøvet ved å påføre det silanerte hexaklorofen på filtermedier, på små gla'ssperler og på en glasskive. Det silanerte hexaklorofen ble kvantitativt bestemt før det ble påført på filtermediet, et hydrotermisk dannet magnesiumsilicat (solgt av søkeren under handelsnavnet "Clearfil") og ble så underkastet en puffervasking med ammo-niumbicarbonat med en pH på 7,0, og mengden av silanert hexaklorofen som ble fjernet,.ble målt. Denne vasking ble så fulgt av en 0,1N alkalisk methanolvasking og en sluttvasking med 1,0 N NaOH ved 70° C. I hvert tilfelle ble en mengde av silanert hexaklorofen i filtratet målt. Den samme fremgangsmåte ble anvendt for belegningen av små glassperler og glass-Skivene. Ca. 50 % av det opprinnelige silanerte hexaklorofen bundet på de kiselsyreholdige materialer ble tilbake selv etter utstrakt kjemisk vasking med varm alkali. The adhesion of silanated hexachlorophene carried out according to Example 1 above was tested by applying the silanated hexachlorophene to filter media, to small glass beads and to a glass disc. The silanated hexachlorophene was quantitatively determined before being applied to the filter media, a hydrothermally formed magnesium silicate (sold by the applicant under the trade name "Clearfil") and then subjected to a buffer wash with ammonium bicarbonate at a pH of 7.0, and the amount of silanated hexachlorophene which was removed,.was measured. This washing was then followed by a 0.1 N alkaline methanol wash and a final wash with 1.0 N NaOH at 70° C. In each case, an amount of silanated hexachlorophene in the filtrate was measured. The same procedure was used for the coating of small glass beads and glass disks. About. 50% of the original silanated hexachlorophene bound on the siliceous materials remained even after extensive chemical washing with hot alkali.
Siliciumbindingen av de silanerte antibiotica ifølge oppfinnelsen muliggjør en rekke antimicrobielle anvendelser hvor binding av det antimicrobielle middel til en kiselsyre-holdig overflate er viktig. Eksempler på noen av disse anvendelser innbefatter belegningen av en rekke beholdere for drikkevarer, matvarer, legemidler og lignende, slik som glassflasker, blikkbokser eller pakninger med en innvendig overflate eller foring på hvilken silangruppen av det silanerte antimicrobielle middel vil hefte ved. Videre kan de silanerte antimicrobielle midler påføres på gulv og vegger av fliser eller andre materialer i sykehus, skoler, badeværelser, kjøkkener og lignende. De silanerte antimicrobielle midler kan også belegges på filtermedier som sand, diatoméjord, asbester eller andre kiselsyreholdige materialer, på glassperler eller på kjemisk apparatur The silicon binding of the silanated antibiotics according to the invention enables a number of antimicrobial applications where binding of the antimicrobial agent to a silicic acid-containing surface is important. Examples of some of these applications include the coating of a variety of containers for beverages, foodstuffs, pharmaceuticals and the like, such as glass bottles, tin cans or packages with an inner surface or lining to which the silane group of the silanated antimicrobial agent will adhere. Furthermore, the silanated antimicrobial agents can be applied to floors and walls made of tiles or other materials in hospitals, schools, bathrooms, kitchens and the like. The silanated antimicrobial agents can also be coated on filter media such as sand, diatomaceous earth, asbestos or other siliceous materials, on glass beads or on chemical apparatus
som raschig-ringer for væskebehartdling. Foruten vedheftningen av de silanerte antimicrobielle midler til kiselsyreholdige overflater, er det også mulig å påføre, de silanerte antibi-crobielle^forbindelser i eller på tekstiler, cellulosefiltere, lær, eller på metaller eller andre slike overflater. De silanerte antimicrobielle forbindelser ifølge oppfinnelsen kan på-føres på tallerkener eller glassvarer fra et vandig medium, as raschig rings for liquid hardening. Besides the adhesion of the silanated antimicrobial agents to silicic acid-containing surfaces, it is also possible to apply the silanated antimicrobial compounds in or on textiles, cellulose filters, leather, or on metals or other such surfaces. The silanated antimicrobial compounds according to the invention can be applied to plates or glassware from an aqueous medium,
f.eks. når tallerkener vaskes i et sykehus eller en restaurant kan den silanerte antimicrobielle forbindelse påføres som en e.g. when dishes are washed in a hospital or restaurant, the silanated antimicrobial compound can be applied as a
del av vaskeoperasjonen.part of the washing operation.
For å prøve den antimicrobielle virkning av de ovenstående silanerte forbindelser ble følgende fremgangsmåte anYandt. En friskt fremstilt microbekultur ble fortynnet til ca. IO<4>- IO<5>celler pr. ml. Til hver fortynning ble tilsatt 6 dråper av et fuktemiddel ("Makon 10") og 0,5 ml prøver av fortynningen ble så pipettert på en rekke petriskåler. Petriskålene var behandlet med silanerte antimicrobielle forbindelser som vist i tabell I nedenfor idet kontrollprøvene var rene og ubehandlet. Petriskålene med de pipetterte kulturer, ble hvirvlet slik at den microbielle suspensjon ble jevnt fordelt og fikk derpå lov til å stå i ca. 30 minutter. Deretter ble 10 ml fosfatpufferoppløsning tilsatt til kontroll-petriskålene. Skålene ble igjen hvirvlet og skålene ble så overtrukket ved helning med MYGP for gjær og PCA for bakterier. MYGP er en • agarblanding hvor hver liter inneholder 3 g gjærekstrakt, 3 g maltekstrakt, 5 g pepton, 10 g dextrose og 10 g agar. PCA er en platetelleragar. Petriskålene behandlet med silanerte antimicrobielle belegg ble direkte dekket med media ved helning under anvendelse av MYGP for gjær og PCA for bakterier. Duplikatplatetellinger ble gjort for hver mikroorganisme. Resultatene er angitt i tabell I med antallet av mikroorganis-mer tellet for kontroll-petriskålene og behandlet med silanerte antimicrobielle forbindelser vist som antallet av mikro-organismer pr. milliliter. In order to test the antimicrobial action of the above silanated compounds, the following procedure was adopted. A freshly prepared microbe culture was diluted to approx. IO<4>- IO<5> cells per ml. To each dilution, 6 drops of a wetting agent ("Makon 10") were added and 0.5 ml samples of the dilution were then pipetted onto a series of Petri dishes. The Petri dishes were treated with silanated antimicrobial compounds as shown in Table I below, while the control samples were clean and untreated. The Petri dishes with the pipetted cultures were swirled so that the microbial suspension was evenly distributed and were then allowed to stand for approx. 30 minutes. Then 10 ml of phosphate buffer solution was added to the control Petri dishes. The dishes were vortexed again and the dishes were then coated by pouring with MYGP for yeast and PCA for bacteria. MYGP is an • agar mixture where each liter contains 3 g of yeast extract, 3 g of malt extract, 5 g of peptone, 10 g of dextrose and 10 g of agar. PCA is a plate counter agar. The Petri dishes treated with silanated antimicrobial coatings were directly covered with media by pouring using MYGP for yeast and PCA for bacteria. Duplicate plate counts were done for each microorganism. The results are given in Table I with the number of micro-organisms counted for the control Petri dishes and treated with silanated antimicrobial compounds shown as the number of micro-organisms per milliliters.
Resultatene av tabell I viser betraktelig antimicrobiell virkning fremdeles bibeholdt av den silanerte antimicrobielle forbindelse med utmerkede bindingsegenskaper til petri-skålen. Som det kunne ventes, kan den antimicrobielle aktivitet av hver silanert forbindelse variere med mikroorganismen fra plate til plate. I andre prøver var tellingen selv for én plate betraktelig forskjellig fra den annen plate, på grunn av forsøksfeil eller vanskeligheter med å gjenvinne microorganismene fra de behandlede overflater, eller variasjoner i tørring og tidsbedømmelse. The results of Table I show considerable antimicrobial activity still retained by the silanated antimicrobial compound with excellent binding properties to the petri dish. As might be expected, the antimicrobial activity of each silanated compound may vary with the microorganism from plate to plate. In other samples, the count even for one plate was significantly different from the other plate, due to experimental error or difficulty in recovering the microorganisms from the treated surfaces, or variations in drying and timing.
For å prøve vedvarenheten av den antimicrobielle virkning etter vasking ble petriskåler behandlet med silanert hexaklorofen og 2,4,4'-triklor-2'-hydroxyfenylether (THDP). Petriskålene ble tørket ved 40° C over natten og så vasket i en 4 %-ig oppløsning av natriumhydroxyd ved 70° C i 20 minutter og derpå skyldet med springvann. Natriumhydroxydvaskingen og vannskyldesyklusen ble så gjentatt 5 ganger og de behandlede og vaskede petriskåler ble tørket ved 4 0° C i 1 time før prø-ving. Kulturer fremstilt som ovenfor ble så inokulert på petriskålene og antallet av microorganismer på duplikatskåler ble tellet opp etter henstand i ca. 3 0 minutter. To test the persistence of the antimicrobial action after washing, Petri dishes were treated with silanated hexachlorophene and 2,4,4'-trichloro-2'-hydroxyphenyl ether (THDP). The Petri dishes were dried at 40°C overnight and then washed in a 4% solution of sodium hydroxide at 70°C for 20 minutes and then rinsed with tap water. The sodium hydroxide wash and water rinse cycle was then repeated 5 times and the treated and washed Petri dishes were dried at 40°C for 1 hour before testing. Cultures prepared as above were then inoculated onto the Petri dishes and the number of microorganisms on duplicate dishes was counted after standing for approx. 30 minutes.
Resultatene av disse- prøver er angitt i tabell II The results of these tests are given in Table II
Fra resultatene vist i tabell II er det åpenbart at de silanerte forbindelser har sterke antimicrobielle egenskaper selv etter gjentatt varm alkalivasking.. Dette indikerer at beleggene av silanerte antimicrobielle forbindelser ifølge oppfinnelsen når de påføres på tallerkener, glåssvarer, vegger og lignende, kan motstå varme vaskinger og fremdeles bibeholde sine. antimicrobielle egenskaper. Det viser også at seigheten av silanbindingen ville gjøre det nødvendig å påføre en tynn film av silanert antimicrobiell forbindelse på keramiske fliser, tallerkener eller lignende bare periodisk, og at når anvendt som en f6ring i flasker, kunne ingen betraktelig mengde lett fjernes fra flaskeoverflaten. From the results shown in Table II, it is obvious that the silanated compounds have strong antimicrobial properties even after repeated hot alkali washing. This indicates that the coatings of silanated antimicrobial compounds according to the invention when applied to plates, glassware, walls and the like can withstand hot washing and still retain theirs. antimicrobial properties. It also shows that the toughness of the silane bond would make it necessary to apply a thin film of silanated antimicrobial compound to ceramic tiles, plates or the like only periodically, and that when used as a liner in bottles, no appreciable amount could be easily removed from the bottle surface.
Et foretrukket kommersielt preparat er en blanding av silanert hexaklorofen og THDP. For å prøve effektiviteten av den silanerte blanding ble de følgende prøver utført. Blandet silanert hexaklorofen og THDP ble . påført fra fortyn-nede methanol- og vannoppløsninger på petriskåler med et fuktemiddel i en mengde av 0,5 ml på hver skål. Kontroll-petriskålene ble behandlet som i prøven angitt i tabell I ovenfor. Alle petriskåler ble så inokulert, hensatt i 30 minutter og ble . så påført medium i duplikat. Resultatene er vist i tabell III nedenfor. A preferred commercial preparation is a mixture of silanated hexachlorophene and THDP. To test the effectiveness of the silanized mixture, the following tests were carried out. Mixed silanated hexachlorophene and THDP were . applied from dilute methanol and water solutions to Petri dishes with a wetting agent in an amount of 0.5 ml on each dish. The control Petri dishes were treated as in the sample indicated in Table I above. All Petri dishes were then inoculated, set aside for 30 minutes and were . then applied medium in duplicate. The results are shown in Table III below.
Som vist i tabell,III oppviser kontrollprøvene et .meget betraktelig antall microorganismer mens kombinasjonen av silanert hexaklorofen og silanert THDP ikke viste noen microorganismer for duplikatplatene fra 1 ml eller 0,1 ml prøver av gjenvinningspufferen. As shown in Table III, the control samples show a very considerable number of microorganisms while the combination of silanated hexachlorophene and silanated THDP showed no microorganisms for the duplicate plates from 1 ml or 0.1 ml samples of the recovery buffer.
For ytterligere å prøve effektiviteten av blandet silanert hexaklorofen og THDP som et kommersielt produkt for antimicrobiell behandling av overflater, ble petriskålene igjen behandlet med en blanding som for tabell III oven, og tørret ved 40° C i 24 timer. Petriskålene ble så vasket med methanol og vann, hvilket ville fjerne eventuelt ubundet antimicrobielt materiale* Microorganismene, i suspensjon, og fuktemiddel ble påført i en mengde på00,5 ml på hver plate som ble så avlest i duplikat for kontrol.lprøvene og behandlede plater. Resultatene er angitt i tabell IV nedenfor . To further test the effectiveness of mixed silanated hexachlorophene and THDP as a commercial product for antimicrobial surface treatment, the Petri dishes were again treated with a mixture as in Table III above and dried at 40°C for 24 hours. The Petri dishes were then washed with methanol and water, which would remove any unbound antimicrobial material* The microorganisms, in suspension, and wetting agent were applied in an amount of 0.5 ml to each plate which was then read in duplicate for the control samples and treated plates. The results are set out in Table IV below.
Igjen eliminerte kombinasjonen av silanert hexaklorofen og silanert THDP effektivt microorganismene på for-søkspiatene, og det er demonstrert at de silanerte derivater er bundet til glassubstratene. Again, the combination of silanated hexachlorophene and silanated THDP effectively eliminated the microorganisms on the test surfaces, and it has been demonstrated that the silanated derivatives are bound to the glass substrates.
De antimicrobielle forbindelser ifølge oppfinnelsen kan anvendes alene eller i kombinasjon for å få et bredt spektrum av antimicrobiell virkning. Effektiviteten mot bakterier, fungi, gjær og lignende varierer fra forbindelse til forbindelse, og således kan de antimicrobielle silanerte forbindelser anvendes alene for en spesifik antimicrobiell funksjon eller i kombinasjon av to eller flere forbindelser for antimicrobiell virkning mot en rekke microorganismer. The antimicrobial compounds according to the invention can be used alone or in combination to obtain a broad spectrum of antimicrobial action. The effectiveness against bacteria, fungi, yeast and the like varies from compound to compound, and thus the antimicrobial silanated compounds can be used alone for a specific antimicrobial function or in combination with two or more compounds for antimicrobial action against a number of microorganisms.
Ovenstående eksempler og prøver er for å belyse oppfinnelsen og må ikke utlegges som begrensende. The above examples and samples are to illustrate the invention and must not be interpreted as limiting.
Foreliggende oppfinnelse fremskaffer derfor et effektivt silanert antimicrobielt preparat som er istand til å bindes over silangruppen til en rekke overflater som glass, polymere materialer, keramikk og lignende. Således kan det silanerte antimicrobielle preparat anvendes ved pakning eller ved fremstilling av farmasøytica, matvarer<p>g drikkevarer for til å begynne med å nedsette mikrobeforurensning ved vedheftning av det silanerte germicid til produksjonsutstyr, filtere, inn-palcningsmaterialer og særlig blikkbokser eller flasker hvori materialer skal lagres. Ved den sistnevnte anvendelse er det derfor ikke nødvendig å anvende ét antimicrobielt middel i pak-ningsmaterialet. Det silanerte antimicrobielle preparat ifølge oppfinnelsen vil også adhere til porselen og stentøy ved avsetning, f.eks. fra et vandig medium med meget sterke bindingsegenskaper til å motstå fjernelse ved varme, alkaliske vannvaskinger. Det silanerte antimicrobielle preparat kan følgelig anvendes for å belegge tallerkener, kopper og andre spiseredskaper og gjenstander anvendt for fremstilling av mat. Andre anvendelser omfatter opprettholdelsen av sterilitet, av medisinsk og dentalt utstyr eller andre anvendelser i sykehus hvor en vedvarende antimicrobiell funksjon ønskes. The present invention therefore provides an effective silanized antimicrobial preparation which is able to be bound via the silane group to a number of surfaces such as glass, polymeric materials, ceramics and the like. Thus, the silanated antimicrobial preparation can be used in packaging or in the production of pharmaceuticals, foodstuffs<p>g beverages to initially reduce microbial contamination by adhering the silanated germicide to production equipment, filters, packaging materials and especially tin cans or bottles in which materials must be stored. In the latter application, it is therefore not necessary to use an antimicrobial agent in the packaging material. The silanated antimicrobial preparation according to the invention will also adhere to porcelain and stoneware upon deposition, e.g. from an aqueous medium with very strong binding properties to resist removal by hot, alkaline water washes. The silanated antimicrobial preparation can therefore be used to coat plates, cups and other eating utensils and objects used for the preparation of food. Other applications include the maintenance of sterility, of medical and dental equipment or other applications in hospitals where a persistent antimicrobial function is desired.
Claims (23)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US50102274A | 1974-08-28 | 1974-08-28 | |
US05/501,058 US3940430A (en) | 1974-08-28 | 1974-08-28 | Silanized antimicrobial compounds |
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NO752938L true NO752938L (en) | 1976-03-02 |
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NO752938A NO752938L (en) | 1974-08-28 | 1975-08-27 |
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JP (1) | JPS5167731A (en) |
AU (1) | AU8433475A (en) |
DE (1) | DE2538341A1 (en) |
DK (1) | DK384775A (en) |
FR (1) | FR2283144A1 (en) |
IT (1) | IT1052139B (en) |
NL (1) | NL7510170A (en) |
NO (1) | NO752938L (en) |
SE (1) | SE7509551L (en) |
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DE2847400A1 (en) * | 1978-11-02 | 1980-05-08 | Dynamit Nobel Ag | SALINE AMINORGANOSILANESTER-PHENOL ADDUCT AND PROCESS FOR THEIR PREPARATION |
EP1285926B1 (en) * | 2001-08-06 | 2004-05-12 | Degussa AG | Organosilicon compounds |
WO2003017962A1 (en) * | 2001-08-24 | 2003-03-06 | Unilever N.V. | Oral composition comprising an alkylhydroxybenzoate |
JP6215476B2 (en) * | 2014-08-07 | 2017-10-18 | シャープ株式会社 | Heat exchanger having fins with sterilizing surface, metal member having sterilizing surface, sterilization method using fin surface of heat exchanger, electric water heater having metal member, and beverage feeder And lunch box lid |
-
1975
- 1975-08-27 NO NO752938A patent/NO752938L/no unknown
- 1975-08-27 AU AU84334/75A patent/AU8433475A/en not_active Expired
- 1975-08-27 DK DK384775A patent/DK384775A/en unknown
- 1975-08-28 DE DE19752538341 patent/DE2538341A1/en active Pending
- 1975-08-28 SE SE7509551A patent/SE7509551L/en unknown
- 1975-08-28 FR FR7526554A patent/FR2283144A1/en not_active Withdrawn
- 1975-08-28 NL NL7510170A patent/NL7510170A/en not_active Application Discontinuation
- 1975-08-28 IT IT51090/75A patent/IT1052139B/en active
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FR2283144A1 (en) | 1976-03-26 |
SE7509551L (en) | 1976-03-01 |
JPS5167731A (en) | 1976-06-11 |
DK384775A (en) | 1976-02-29 |
NL7510170A (en) | 1976-03-02 |
DE2538341A1 (en) | 1976-03-11 |
AU8433475A (en) | 1977-03-03 |
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