JPH0474026B2 - - Google Patents
Info
- Publication number
- JPH0474026B2 JPH0474026B2 JP58188940A JP18894083A JPH0474026B2 JP H0474026 B2 JPH0474026 B2 JP H0474026B2 JP 58188940 A JP58188940 A JP 58188940A JP 18894083 A JP18894083 A JP 18894083A JP H0474026 B2 JPH0474026 B2 JP H0474026B2
- Authority
- JP
- Japan
- Prior art keywords
- water
- soluble
- antibacterial agent
- catheter
- urinary
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000003242 anti bacterial agent Substances 0.000 claims description 41
- 230000002485 urinary effect Effects 0.000 claims description 24
- -1 biguanide compound Chemical class 0.000 claims description 19
- 229920002379 silicone rubber Polymers 0.000 claims description 17
- 239000004945 silicone rubber Substances 0.000 claims description 17
- 125000002091 cationic group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 238000013268 sustained release Methods 0.000 claims description 10
- 239000012730 sustained-release form Substances 0.000 claims description 10
- 229940123208 Biguanide Drugs 0.000 claims description 5
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 229920001971 elastomer Polymers 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 210000001635 urinary tract Anatomy 0.000 description 7
- 210000002700 urine Anatomy 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 208000019206 urinary tract infection Diseases 0.000 description 6
- 150000001251 acridines Chemical class 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 150000004283 biguanides Chemical class 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229920001296 polysiloxane Polymers 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 159000000007 calcium salts Chemical group 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000011247 coating layer Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940050410 gluconate Drugs 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000001451 organic peroxides Chemical class 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 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 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000000645 desinfectant Substances 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229910021485 fumed silica Inorganic materials 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000010077 mastication Methods 0.000 description 2
- 230000018984 mastication Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- OXYKVVLTXXXVRT-UHFFFAOYSA-N (4-chlorobenzoyl) 4-chlorobenzenecarboperoxoate Chemical group C1=CC(Cl)=CC=C1C(=O)OOC(=O)C1=CC=C(Cl)C=C1 OXYKVVLTXXXVRT-UHFFFAOYSA-N 0.000 description 1
- PAOHAQSLJSMLAT-UHFFFAOYSA-N 1-butylperoxybutane Chemical group CCCCOOCCCC PAOHAQSLJSMLAT-UHFFFAOYSA-N 0.000 description 1
- NIMNIJHOINCSAH-UHFFFAOYSA-N 1-ethoxyacridine Chemical compound C1=CC=C2C=C3C(OCC)=CC=CC3=NC2=C1 NIMNIJHOINCSAH-UHFFFAOYSA-N 0.000 description 1
- DMWVYCCGCQPJEA-UHFFFAOYSA-N 2,5-bis(tert-butylperoxy)-2,5-dimethylhexane Chemical group CC(C)(C)OOC(C)(C)CCC(C)(C)OOC(C)(C)C DMWVYCCGCQPJEA-UHFFFAOYSA-N 0.000 description 1
- XMNIXWIUMCBBBL-UHFFFAOYSA-N 2-(2-phenylpropan-2-ylperoxy)propan-2-ylbenzene Chemical compound C=1C=CC=CC=1C(C)(C)OOC(C)(C)C1=CC=CC=C1 XMNIXWIUMCBBBL-UHFFFAOYSA-N 0.000 description 1
- IYLLULUTZPKQBW-UHFFFAOYSA-N Acrinol Chemical compound CC(O)C(O)=O.C1=C(N)C=CC2=C(N)C3=CC(OCC)=CC=C3N=C21 IYLLULUTZPKQBW-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- QWZLBLDNRUUYQI-UHFFFAOYSA-M Methylbenzethonium chloride Chemical compound [Cl-].CC1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 QWZLBLDNRUUYQI-UHFFFAOYSA-M 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 235000017284 Pometia pinnata Nutrition 0.000 description 1
- 240000007653 Pometia tomentosa Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- PLZVEHJLHYMBBY-UHFFFAOYSA-N Tetradecylamine Chemical class CCCCCCCCCCCCCCN PLZVEHJLHYMBBY-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 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 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical class CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 description 1
- WNBGYVXHFTYOBY-UHFFFAOYSA-N benzyl-dimethyl-tetradecylazanium Chemical class CCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 WNBGYVXHFTYOBY-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 238000005266 casting Methods 0.000 description 1
- QDYLMAYUEZBUFO-UHFFFAOYSA-N cetalkonium chloride Chemical class CCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 QDYLMAYUEZBUFO-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 239000012975 dibutyltin dilaurate Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- SIYLLGKDQZGJHK-UHFFFAOYSA-N dimethyl-(phenylmethyl)-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]ammonium Chemical class C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 SIYLLGKDQZGJHK-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 208000005053 encephalomalacia Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 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 description 1
- 229960004068 hexachlorophene Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- LAQFLZHBVPULPL-UHFFFAOYSA-N methyl(phenyl)silicon Chemical compound C[Si]C1=CC=CC=C1 LAQFLZHBVPULPL-UHFFFAOYSA-N 0.000 description 1
- 229960002285 methylbenzethonium chloride Drugs 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 239000010815 organic waste Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000000913 palmityl 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])C([H])([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
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000012763 reinforcing filler Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
- 229920002050 silicone resin Polymers 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- GJBRNHKUVLOCEB-UHFFFAOYSA-N tert-butyl benzenecarboperoxoate Chemical group CC(C)(C)OOC(=O)C1=CC=CC=C1 GJBRNHKUVLOCEB-UHFFFAOYSA-N 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- CPUDPFPXCZDNGI-UHFFFAOYSA-N triethoxy(methyl)silane Chemical compound CCO[Si](C)(OCC)OCC CPUDPFPXCZDNGI-UHFFFAOYSA-N 0.000 description 1
- 208000000143 urethritis Diseases 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Description
（産業上の利用分野）
本発明は、抗菌剤徐放性導尿カテーテルに関す
るものである。
（従来の技術）
脊髄損傷、脳出血、脳軟化症あるいは手術後の
患者においては排尿困難、尿失禁等の症状を伴う
ことが多い。このような場合は、円滑な尿路を確
保し、腎機能の維持や改善を促すか、あるいは尿
の漏出を防止するといつた意味で導尿カテーテル
が広く使用されている。しかし、導尿カテーテル
は長期間尿路内に留置しておくため、このカテー
テルの管内外を通じて細菌が侵入し、尿道炎、膀
胱炎、腎う炎等の感染が高頻度に発生することが
知られている。この対策として、従来は膀胱の洗
浄や殺菌剤の注入あるいは抗生物質の予防的投与
も行われているが、これらは余分な操作を必要と
するばかりでなく、効果が不確実である。このた
め、最近では導尿カテーテル設置局所での細菌感
染を根本的に防止するために、抗菌剤が局所にお
いて一定速度で長期間徐放されるタイプの導尿カ
テーテルの出現が強く望まれている。
導尿カテーテルを構成する素材に要求される特
性としては、その使用目的や使用形態からして適
度な柔軟性、耐水性、生体適合性、無毒性、挿入
のしすさ、カルシウム塩等の沈着がないことが挙
げられる。現在、最も多く使われている素材はコ
スト的に最も安価な天然ゴムであるが、その欠点
として例えば耐水性に劣るため１週間以上の長期
の体内留置に向かないこと、生体適合性が不良で
尿路粘膜等の炎症をもたらすこと、挿入が円滑に
行われないこと、カテーテルの管内外表面上への
カルシウムやその他塩類の沈着に伴う流路の閉塞
も抜去が難しくなること等が挙げられる。その点
シリコーンゴムはコスト的に高価であるが、上記
欠点を補うものとして近年急速に注目されつつあ
る素材である。
シリコーンゴム製導尿カテーテルに抗菌性を賦
与する方法として、現在までに次のような方法が
提案されている。例えば米国特許第3566874号及
び第3695921号明細書には、カテーテルに親水性
のアクリレート又はメタクリレートのモノマー又
はオリゴマーを含浸させ、その後、重合を完結さ
せることによりカテーテルの外面上に親水性のコ
ーテイング層を施し、その部分に抗生物質や殺菌
剤を含浸させる方法が記載されている。
また、米国特許第4055682号明細書には親水性
のＮ−ビニルピロリドン等を含浸させ、その後放
射線照射を行うことによりシリコーンにグラフト
重合させ、その部分に塩化ベンザルコニウムやヘ
キサクロロフエンや沃素等を含浸させる方法が記
載されている。また、特開昭49−34179号公報や
特開昭49−34180号公報には、それぞれ親水性重
合体としてアクリルアミド系単量体を重合させた
ものやポリビニルアルコールで被覆したカテーテ
ルが提案されている。しかしながら、これらはい
ずれもカテーテル外面上に親水性樹脂よりなるコ
ーテイング層又は被覆層を設け、その部分に抗菌
剤を物理的に吸着させたものであるから、これら
のタイプのカテーテルに共通する欠点として、(1)
抗菌剤が早期に尿中に溶出、拡散してしまうた
め、長期の抗菌活性が得られないこと、(2)親水性
の被覆層に尿等の体液が吸収されて塩濃度が飽和
状態になるとともに、その部分に核を生じ、カル
シウム塩やその他固形物が析出し、カテーテルが
詰まつたり、外面上に付着を生ずること等が指摘
されている。
（発明が解決しようとする課題）
本発明者らは、以上のような技術的背景をふま
えた上でシリコーンゴムとしての特性を生かしな
がら、長期の体内留置期間中においても***
防止に必要な一定濃度以上の抗菌剤を徐放し続
け、また、塩類の付着や閉塞のないシリコーンゴ
ム製の抗菌剤徐放性導尿カテーテルを提供するこ
とを目的として、鋭意検討の結果、シリコーンゴ
ム中に特定の抗菌剤を含有せしめることによつて
上記の目的が達成されることを見い出し、本発明
に到達したものである。
（課題を解決するための手段）
すなわち、本発明は、水溶性のカチオン型抗菌
剤を含有するシリコーンゴムからなる抗菌剤徐放
性導尿カテーテルを要旨とするものである。
従来、ポリマーのマトリツクス構造内に活性物
質を分散させたものとしては種々の組合せのもの
が知られているが、この場合、マトリツクス成分
とフイラー成分の物理的性質又は化学的性質の差
異や両成分間の相互作用により、目的とする機能
を有するものを得ることは必ずしも容易ではなか
つた。むしろ、その混合操作の容易さと比べる
と、一般的にはむしろ困難を伴うのが通例であ
り、成功例も少ない。しかるに、本発明はシリコ
ーンゴムからなる導尿カテーテルのシリコーンゴ
ム中に水溶性のカチオン型抗菌剤を分散させたも
のが、シリコーンゴムとしての特性を失うことな
く、尿のような比較的高濃度の塩や有機老廃物あ
るいはタンパク等を含む体液に触れた場合でも、
長期にわたり尿中に抗菌剤を徐放し続けること及
びカルシウム塩等の析出や沈着による閉塞が認め
られないという発見に基づいており、このような
例は今までに報告されていない。このような、水
溶性のカチオン型抗菌剤がシリコーンゴムのよう
な疎水性の強いマトリツクス中に均一に分散さ
れ、なおかつ長期にわたり徐放性を示す理由につ
いては明らかでない。しかし、分散性については
水溶性のカチオン型抗菌剤は水溶性の状態では均
一であり、これをシリコーンゴム生ゴムに混合す
るので、よい分散性が得られるものと思われる。
本発明の抗菌剤徐放性導尿カテーテルを製造す
るには、例えば高重合度のオルガノポリシロキサ
ンよりなる生ゴムに充填剤及び加硫剤を混合した
コンパウンドと、水溶性のカチオン型抗菌剤とか
らなる組成物又はこれにさらに分散促進剤、顔料
等の添加剤が混合された組成物を成形すればよ
い。より具体的には、例えば、生ゴムの素練り段
階において、充填剤、加硫剤及び水溶性のカチオ
ン型抗菌剤を添加、混合したのち、押し出し成形
するか又は圧縮成形すればよい。素練りや成形に
は従来公知の種々の装置及び方法を適宜採用する
ことができる。
オルガノポリシロキサンとしては、ジメチルポ
リシロキサン、メチルフエニルポリシロキサン、
メチルビニルポリシロキサン、フロロアルキルメ
チルポリシロキサン等が好ましく用いられる。充
填剤としては、補強性充填剤としてのシリカ微粉
末が代表的であるが、例えば炭酸カルシウム、酸
化チタン、酸化亜鉛等も用いられる。また、これ
ら充填剤の分散促進剤としては、例えばシリコン
レジン類、アルコキシシラン及びシロキサン類、
ヒドロキシシラン及びシロキサン類、有機酸エス
テル類、多価アルコール類等が用いられる。加硫
剤としては有機過酸化物、脂肪酸、アゾ化合物、
白金、パラジウム、イオウが用いられるが、好ま
しいのは有機過酸化物である。有機過酸化物とし
ては、ベンゾイルパーオキサイド、ビス−２，４
−ジクロロベンゾイルパーオキサイド、ジクミル
パーオキサイド、ジターシヤリブチルパーオキサ
イド、ターシヤリブチルパーベンゾエート、ｐ−
モノクロルベンゾイルパーオキサイド、２，５−
ジメチル−２，５−ビス（ターシヤルブチルパー
オキシ）ヘキサン等が好ましく用いられる。本発
明において使用する抗菌剤がその加硫温度に耐え
るものである場合は、熱加硫型シリコーンゴムを
使用してもよいが、そうでない場合には室温加硫
型シリコーンゴムを用いることが好ましい。
本発明における水溶性のカチオン型抗菌剤と
は、分子内に正電荷と疎水基をもつ抗菌剤をい
い、好ましい具体例としては水溶性のビグアニド
化合物又はビグアニド化合物の水溶性の塩、水溶
性のアクリジン化合物又はアクリジン化合物の水
溶性の塩、水溶性の第４級アンモニウム塩系化合
物等が挙げられる。
ビグアニド化合物とは、下記の一般式（）又
は（）又は（）で示されるものである。
ここで、Ｒはアルキル基、アミノアルキル基、
フエニル基、アルキルフエニル基、ハロゲン化フ
エニル基、ハイドロキシフエニル基、メトキシフ
エニル基、カルボキシフエニル基、ナフチル基又
はニトリル基であり、R′は水素又はアルキル基
である。なお、ｍ及びｎは正の整数であるが、２
〜10の範囲が好適である。本発明で使用される水
溶性のビグアニド化合物又はビグアニド化合物の
水溶性の塩の好適な具体例を挙げれば、１，６−
ジ−（４−クロロフエニルビグアニド）ヘキサン
グルコネート等である。
アクリジン化合物とは、下記のアクリジン骨格
（）を有する化合物であり、「大有機化学」第16
巻第286〜326頁（朝倉書店、昭和34年）に種々の
誘導体が記載されている。
本発明で使用される水溶性のアクリジン化合物
又はアクリジン化合物の水溶性の塩の好適な具体
例としては、６，９−ジアミノ−２−エトキシア
クリジン乳酸塩等が挙げられる。
第４級アンモニウム塩とは、下記の構造式
（）で示されるものである。
ここで、R1，R2，R3及びR4はアルキル基、ベ
ンジル基、カルボキシアルキル基、アルキル基又
はニトロ基又はクロル原子等で置換したベンジル
基、ヒドロキシアルキル基、アセトキシアルキル
基、アルキルフエノキシアルコキシアルキル基等
である。Encyclopedia of Chemical
Technology第19巻、第521〜531頁（1932年，
Wiley International Publication）西、今井、
笠井共編「界面活性剤便覧」第737〜747頁（1960
年、産業図書）、R.S.Sheltonほか、Journal of
American Chemacal Society、第68巻、第753
〜759頁（1964年）に、R1，R2，R3，R4を組み
合わせた種々の第４級アンモニウム塩が記載され
ているが、これらのなかでも、R1がベンジル基、
R2及びR3がメチル基、R4がドデシル基であるベ
ンジルジメチルドデシルアンモニウム塩、R1が
ベンジル基、R2及びR3がメチル基、R4がテトラ
デシル基であるベンジルジメチルテトラデシルア
ンモニウム塩、R1がベンジル基、R2及びR3がメ
チル基、R4がヘキサデシル基であるベンジルジ
メチルヘキサデシルアンモニウム塩、R1，R2及
びR3がメチル基、R4がテトラデシル基であるト
リメチルテトラデシルアンモニウム塩ならびに
（２−（２−ｐ−（１，１，３，３−テトラメチル
ブチル）フエノキシ）エトキシ）エチルであるベ
ンゼトニウム塩等が本発明において好ましく使用
される水溶性第４級アンモニウム塩として挙げら
れる。Ｘとしては、通常のクロライド、ブロマイ
ド、アイオダイド、サイトレート、サルフエー
ト、ホスフエート、ボレート等である。また、
R1，R2，R3，R4の中の一つがポリマー主鎖であ
り、これら第４級アンモニウム塩が側鎖に組み込
まれた型のポリマー型第４級アンモニウム塩化合
物も本発明において同様に有効である。
導尿カテーテルにおいてもその体内留置期間中
において、抗菌剤が一定速度で放出され続けるこ
と、すなわち、ゼロ・オーダー・リリース（zero
order release）が好ましいことは言うまでもな
い。抗菌剤のいわゆる最小（発育）阻止濃度
（Minimal Inhibitory Concentration）以上の異
常放出は経済的に不利であるばかりでなく、尿路
や膀胱内の粘膜に対し、副作用としての炎症をも
たらすことになり、好ましくない。一般的にポリ
マーマトリツクス内に薬剤を分散させたものはゼ
ロ・オーダー・リリースは困難であるが、本発明
に用いられる水溶性のカチオン型抗菌剤は実質的
にゼロ・オーダー・リリースを実現するもので、
特に水溶性のビグアニド化合物又はビグアニド化
合物の水溶性の塩及び水溶性のアクリジン化合物
又はアクリジン化合物の水溶性の塩及び水溶性の
第４級アンモニウム塩が好ましく用いられる。こ
こでいう水溶性とは、20℃における100ｇの水に
対する溶解度が3.0ｇを超えるものを指す。本発
明に用いる水溶性のカチオン型抗菌剤の中で、特
に好ましく用いられる水溶性の抗菌剤を例示すれ
ば、１，６−ジ−（４−クロロフエニルビグアニ
ド）ヘキサンのグルコン酸塩等、６，９−ジアミ
ノ−２−エトキシアクリジンの乳酸塩、アクラニ
ール（６−クロロ−９−（３−ジエチルアミノ−
２−オキシ）プロピルアミノ−２−メトキシアク
リジン）、ベンジルジメチルテトラデシルアンモ
ニウムクロライド、メチルベンゼトニウムクロラ
イド、ベンゼトニウムクロライド、ベンザルコニ
ウムクロライド等が挙げられる。
本発明における水溶性のカチオン型抗菌剤のシ
リコーンゴム中への配合量はそれぞれの種類や組
合せにより異なるが、一般的にはシリコーンゴム
に対して0.1〜50重量％、より好ましくは0.5〜25
重量％が適当である。この場合、0.1重量％以下
では目的とする抗菌力が十分得にくく、一方、50
重量％以上ではシリコーンゴムのエラストマーと
しての物性が損なわれる傾向がある。
（実施例）
以下、実施例を示し、本発明をさらに具体的に
詳述する。なお、例中、「部」は「重量部」を意
味する。
実施例 １
メチルビニルポリシロキサン生ゴム100部、煙
霧質シリカ25部、ビス−２，４−ジクロルベンゾ
イルパーオキサイド0.5部及び抗菌剤として易水
溶性の１，６−ジ−（４−クロロフエニルビグア
ニド）ヘキサンのグルコン酸塩15部を加え、ゴム
用ロール機でよく素練りしたものを押し出し成形
機にかけ、200℃で２分間加熱することにより外
径５mm、内径３mm、長さ350mmのチユーブを作製
した。これを130℃で１週間、後加硫を施し、以
後常法により導尿カテーテルを作成した。得られ
た導尿カテーテルを37℃の試験尿100ml中に浸漬
し、１日経過後、検定菌としてBacillus subtilis
ATCC6633（培地NUTRIENT AGAR）を用い、
円筒平板法（デイスク法）にて抗菌活性テストを
行い、そこに生じた阻止円の大きさから、あらか
じめ求めておいて検量線より放出された抗菌剤濃
度を求めた。さらに、試験尿を１日毎に新しい試
験尿に取り替えて同様の活性テストを14回まで繰
り返した。このようにして得られた結果を表−１
に示す。
また、カテーテルを実際に５人の患者に臨床応
用したところ、２週間の体内留置においても全例
について***は認められなかつた。また、カ
テーテル内部での固形物の沈着による尿路の閉塞
も認められず、カテーテルの抜去も患者に苦痛を
与えることもなくスムースに行われた。
比較例 １
抗菌剤を含まない市販のシリコーンゴム製導尿
カテーテルを実施例１と同様にして５人の患者に
臨床応用したところ、１人については３日目にお
いて、２人については５日目において、他の１人
においては７日目においてそれぞれ***が認
められた。
実施例 ２
メチルフエニルシリコーン生ゴム100部に煙霧
質シリカ20部、ベンゾイルパーオキサイド0.2部
及び抗菌剤として水溶性の６，９−ジアミノ−２
−エトキシアクリジンの乳酸塩（20℃における水
100ｇに対する溶解度が約５ｇ）20部を加え、ゴ
ム用ロール機でよく素練りしたものを押し出し成
形機にかけ、200℃で２分間加熱することにより
外径５mm、内径３mm、長さ350mmのチユーブを作
製した。これを180℃で２日間、後加硫を施し、
以後常法により導尿カテーテルを作製した。得ら
れた導尿カテーテルについて、実施例１と同じ抗
菌活性テストを行つたところ、表−１に示す結果
を得た。
また、このカテーテルを実際に５人の患者に臨
床応用したところ、３週間の体内留置においても
全例について***は認められなかつた。ま
た、カテーテル内部での固形物の沈着による尿路
の閉塞も認められず、カテーテルの抜去も患者に
苦痛を与えることもなくスムースに行われた。
実施例 ３
末端を水酸基で封鎖したジメチルポリシロキサ
ン100部、シリカエアロゲル10部、メチルトリエ
トキシシラン２部、ジブチルすずジラウレート
0.2部及び抗菌剤として易水溶性のベンジルジメ
チルテトラデシルアンモニウムクロライド10部を
混合後、直ちに注型用金型に流し込み、室温で硬
化させ、外径５mm、内径３mm、長さ350mmのチユ
ーブを作製した。これを用いて常法により導尿カ
テーテルを作製し、実施例１と同様にして抗菌活
性テストを行つたところ、表−１に示す結果が得
られた。
また、このカテーテルを実際に５人の患者に臨
床応用したところ、２週間の体内留置においても
全例について***は認められなかつた。ま
た、カテーテル内部での固形物の沈着による尿路
の閉塞も認められず、カテーテルの抜去も患者に
苦痛を与えることもなくスムースに行われた。
(Industrial Application Field) The present invention relates to an antibacterial agent sustained release urinary catheter. (Prior Art) Patients with spinal cord injury, cerebral hemorrhage, encephalomalacia, or surgery are often accompanied by symptoms such as difficulty in urination and urinary incontinence. In such cases, urinary catheters are widely used to ensure a smooth urinary tract, promote maintenance or improvement of renal function, or prevent urine leakage. However, because urinary catheters are left in the urinary tract for long periods of time, bacteria can enter inside and outside the catheter, leading to frequent infections such as urethritis, cystitis, and nephritis. It is being Conventional countermeasures include bladder irrigation, injection of disinfectants, and prophylactic administration of antibiotics, but these not only require extra operations but also have uncertain effectiveness. Therefore, in order to fundamentally prevent bacterial infection at the site where the urinary catheter is installed, there has been a strong desire for a type of urinary catheter that releases antibacterial agents locally at a constant rate over a long period of time. . The properties required of the materials that make up urinary catheters include appropriate flexibility, water resistance, biocompatibility, non-toxicity, ease of insertion, and deposition of calcium salts, etc., depending on the purpose and form of use. One example is that there is no such thing. Currently, the most commonly used material is natural rubber, which is the cheapest in terms of cost, but its drawbacks include, for example, its poor water resistance, making it unsuitable for long-term placement in the body for more than a week, and its poor biocompatibility. Examples include inflammation of the urinary tract mucosa, etc., difficulty in inserting the catheter smoothly, and obstruction of the flow path due to calcium and other salt deposits on the inner and outer surfaces of the catheter, making removal difficult. Although silicone rubber is expensive in this respect, it is a material that has been rapidly attracting attention in recent years as a material that compensates for the above-mentioned drawbacks. The following methods have been proposed to date for imparting antibacterial properties to silicone rubber urinary catheters. For example, U.S. Pat. Nos. 3,566,874 and 3,695,921 disclose a hydrophilic coating layer on the exterior surface of the catheter by impregnating the catheter with hydrophilic acrylate or methacrylate monomers or oligomers and then completing the polymerization. A method is described in which the area is impregnated with antibiotics and disinfectants. In addition, US Pat. No. 4,055,682 discloses that silicone is graft-polymerized by impregnating it with hydrophilic N-vinylpyrrolidone, etc., and then irradiating it with radiation, and then adding benzalkonium chloride, hexachlorophene, iodine, etc. to the silicone. A method of impregnation is described. In addition, JP-A-49-34179 and JP-A-49-34180 propose catheters coated with polymerized acrylamide monomers and polyvinyl alcohol as hydrophilic polymers, respectively. . However, since all of these catheters have a coating layer made of hydrophilic resin on the outer surface of the catheter, and the antibacterial agent is physically adsorbed to that part, a common drawback of these types of catheters is that ,(1)
(2) Body fluids such as urine are absorbed into the hydrophilic coating layer, resulting in saturated salt concentration. At the same time, it has been pointed out that nucleation occurs in that area, and calcium salts and other solid substances precipitate, clogging the catheter and causing deposits on the external surface. (Problems to be Solved by the Invention) Based on the above technical background, the present inventors have made use of the characteristics of silicone rubber to develop a material that is necessary for preventing urinary tract infections even during long-term indwelling in the body. With the aim of providing an antibacterial agent sustained release urinary catheter made of silicone rubber that continuously releases antibacterial agents at a certain concentration or higher and is free from salt adhesion and blockage, as a result of extensive research, we have found that The present invention was achieved by discovering that the above object can be achieved by incorporating a specific antibacterial agent. (Means for Solving the Problems) That is, the gist of the present invention is an antibacterial agent sustained release urinary catheter made of silicone rubber containing a water-soluble cationic antibacterial agent. Conventionally, various combinations of active substances dispersed within polymer matrix structures have been known, but in this case, differences in physical or chemical properties between the matrix component and filler component, or Due to the interaction between the two, it has not always been easy to obtain something with the desired functionality. Rather, compared to the ease of mixing operations, it is generally more difficult and there are few success stories. However, the present invention has disclosed that a water-soluble cationic antibacterial agent dispersed in the silicone rubber of a urinary catheter made of silicone rubber can be used in relatively high concentrations such as urine without losing its properties as silicone rubber. Even if you come into contact with body fluids containing salt, organic wastes, or proteins,
This method is based on the discovery that the antibacterial agent is continuously released into the urine over a long period of time and that no blockage due to precipitation or deposition of calcium salts is observed, and no such case has been reported to date. It is not clear why such a water-soluble cationic antibacterial agent is uniformly dispersed in a highly hydrophobic matrix such as silicone rubber and exhibits sustained release over a long period of time. However, in terms of dispersibility, the water-soluble cationic antibacterial agent is uniform in its water-soluble state, and since it is mixed with the raw silicone rubber, it is thought that good dispersibility can be obtained. In order to manufacture the antibacterial agent sustained release urinary catheter of the present invention, for example, a compound prepared by mixing raw rubber made of organopolysiloxane with a high degree of polymerization with a filler and a vulcanizing agent, and a water-soluble cationic antibacterial agent are used. What is necessary is to mold a composition in which additives such as a dispersion accelerator and a pigment are further mixed with the composition. More specifically, for example, a filler, a vulcanizing agent, and a water-soluble cationic antibacterial agent may be added and mixed during the mastication stage of raw rubber, and then extrusion molding or compression molding may be performed. Various conventionally known devices and methods can be appropriately employed for mastication and molding. Examples of organopolysiloxane include dimethylpolysiloxane, methylphenylpolysiloxane,
Methylvinylpolysiloxane, fluoroalkylmethylpolysiloxane, and the like are preferably used. As the filler, fine silica powder is typically used as a reinforcing filler, but calcium carbonate, titanium oxide, zinc oxide, etc. may also be used. In addition, examples of dispersion accelerators for these fillers include silicone resins, alkoxysilanes and siloxanes,
Hydroxysilane, siloxanes, organic acid esters, polyhydric alcohols, etc. are used. Vulcanizing agents include organic peroxides, fatty acids, azo compounds,
Platinum, palladium, and sulfur are used, but organic peroxides are preferred. Examples of organic peroxides include benzoyl peroxide, bis-2,4
-dichlorobenzoyl peroxide, dicumyl peroxide, tertiary butyl peroxide, tertiary butyl perbenzoate, p-
Monochlorobenzoyl peroxide, 2,5-
Dimethyl-2,5-bis(tert-butylperoxy)hexane and the like are preferably used. If the antibacterial agent used in the present invention can withstand the vulcanization temperature, heat-vulcanizing silicone rubber may be used, but if not, it is preferable to use room-temperature vulcanizing silicone rubber. . The water-soluble cationic antibacterial agent in the present invention refers to an antibacterial agent having a positive charge and a hydrophobic group in the molecule, and preferred specific examples include water-soluble biguanide compounds, water-soluble salts of biguanide compounds, and water-soluble antibacterial agents. Examples include acridine compounds, water-soluble salts of acridine compounds, and water-soluble quaternary ammonium salt compounds. The biguanide compound is represented by the following general formula () or () or (). Here, R is an alkyl group, an aminoalkyl group,
It is a phenyl group, an alkylphenyl group, a halogenated phenyl group, a hydroxyphenyl group, a methoxyphenyl group, a carboxyphenyl group, a naphthyl group or a nitrile group, and R' is hydrogen or an alkyl group. Note that m and n are positive integers, but 2
A range of ~10 is preferred. Preferred specific examples of the water-soluble biguanide compound or the water-soluble salt of the biguanide compound used in the present invention include 1,6-
Di-(4-chlorophenyl biguanide) hexane gluconate and the like. Acridine compounds are compounds having the following acridine skeleton (), and are
Various derivatives are described in Vol. 286-326 (Asakura Shoten, 1960). Preferred specific examples of the water-soluble acridine compound or water-soluble salt of the acridine compound used in the present invention include 6,9-diamino-2-ethoxyacridine lactate. The quaternary ammonium salt is represented by the following structural formula (). Here, R 1 , R 2 , R 3 and R 4 are alkyl groups, benzyl groups, carboxyalkyl groups, alkyl groups or benzyl groups substituted with nitro groups or chlorine atoms, hydroxyalkyl groups, acetoxyalkyl groups, alkyl groups, etc. Enoxyalkoxyalkyl groups, etc. Encyclopedia of Chemical
Technology Vol. 19, pp. 521-531 (1932,
Wiley International Publication) Nishi, Imai,
"Surfactant Handbook" co-edited by Kasai, pp. 737-747 (1960
Journal of
American Chemical Society, Volume 68, No. 753
759 (1964) describes various quaternary ammonium salts in which R 1 , R 2 , R 3 , and R 4 are combined. Among these, R 1 is a benzyl group,
Benzyldimethyldodecylammonium salt where R 2 and R 3 are methyl groups and R 4 is dodecyl group; benzyldimethyltetradecylammonium salt where R 1 is benzyl group, R 2 and R 3 are methyl groups, and R 4 is tetradecyl group , benzyldimethylhexadecyl ammonium salt where R 1 is a benzyl group, R 2 and R 3 are a methyl group, and R 4 is a hexadecyl group, trimethyl where R 1 , R 2 and R 3 are a methyl group, and R 4 is a tetradecyl group Water-soluble quaternary ammonium salts preferably used in the present invention include tetradecylammonium salts and benzethonium salts such as (2-(2-p-(1,1,3,3-tetramethylbutyl)phenoxy)ethoxy)ethyl. Listed as salt. Examples of X include common chloride, bromide, iodide, citrate, sulfate, phosphate, borate, and the like. Also,
Polymer-type quaternary ammonium salt compounds in which one of R 1 , R 2 , R 3 , and R 4 is a polymer main chain and these quaternary ammonium salts are incorporated into the side chain are also used in the present invention. It is effective for Even in urinary catheters, antibacterial agents continue to be released at a constant rate while they remain in the body, i.e., zero-order release.
Needless to say, order release is preferable. Abnormal release of antibacterial agents in excess of the so-called minimum inhibitory concentration is not only economically disadvantageous, but also causes inflammation of the mucous membranes in the urinary tract and bladder as a side effect. Undesirable. Generally, it is difficult to achieve zero-order release with drugs dispersed within a polymer matrix, but the water-soluble cationic antibacterial agent used in the present invention substantially achieves zero-order release. Something,
In particular, water-soluble biguanide compounds or water-soluble salts of biguanide compounds, water-soluble acridine compounds or water-soluble salts of acridine compounds, and water-soluble quaternary ammonium salts are preferably used. Water-soluble herein refers to a substance whose solubility in 100 g of water at 20°C exceeds 3.0 g. Among the water-soluble cationic antibacterial agents used in the present invention, particularly preferred water-soluble antibacterial agents include 1,6-di-(4-chlorophenylbiguanide)hexane gluconate, etc. , 9-diamino-2-ethoxyacridine lactate, acraneal (6-chloro-9-(3-diethylamino-
(2-oxy)propylamino-2-methoxyacridine), benzyldimethyltetradecylammonium chloride, methylbenzethonium chloride, benzethonium chloride, benzalkonium chloride, and the like. The amount of the water-soluble cationic antibacterial agent incorporated into the silicone rubber in the present invention varies depending on the type and combination, but is generally 0.1 to 50% by weight, more preferably 0.5 to 25% by weight based on the silicone rubber.
Weight % is appropriate. In this case, if it is less than 0.1% by weight, it is difficult to obtain the desired antibacterial activity;
If the amount exceeds % by weight, the physical properties of the silicone rubber as an elastomer tend to be impaired. (Example) Hereinafter, the present invention will be described in more detail with reference to Examples. In addition, in the examples, "part" means "part by weight". Example 1 100 parts of methylvinylpolysiloxane raw rubber, 25 parts of fumed silica, 0.5 parts of bis-2,4-dichlorobenzoyl peroxide, and easily water-soluble 1,6-di-(4-chlorophenyl biguanide) as an antibacterial agent. ) Add 15 parts of hexane gluconate, masticate well with a rubber roll machine, extrude and heat at 200℃ for 2 minutes to make a tube with an outer diameter of 5 mm, an inner diameter of 3 mm, and a length of 350 mm. did. This was post-vulcanized at 130° C. for one week, and then a urinary catheter was prepared using a conventional method. The obtained urinary catheter was immersed in 100 ml of test urine at 37°C, and after one day, Bacillus subtilis was detected as a test bacterium.
Using ATCC6633 (medium NUTRIENT AGAR),
An antibacterial activity test was conducted using the cylindrical plate method (disk method), and the concentration of the antibacterial agent released was determined from the size of the inhibition circle generated in advance using a calibration curve. Furthermore, the same activity test was repeated up to 14 times by replacing the test urine with fresh test urine every day. Table 1 shows the results obtained in this way.
Shown below. Furthermore, when the catheter was actually applied clinically to five patients, no urinary tract infection was observed in any of the patients even after the catheter was left in the body for two weeks. Furthermore, no obstruction of the urinary tract due to solid matter deposited inside the catheter was observed, and the catheter was removed smoothly without causing any pain to the patient. Comparative Example 1 A commercially available silicone rubber urinary catheter that does not contain antibacterial agents was clinically applied to 5 patients in the same manner as in Example 1, and 1 patient was treated on the 3rd day and 2 patients were treated on the 5th day. In one patient, a urinary tract infection was observed on the seventh day. Example 2 100 parts of methylphenyl silicone raw rubber, 20 parts of fumed silica, 0.2 parts of benzoyl peroxide and water-soluble 6,9-diamino-2 as an antibacterial agent.
- Lactate of ethoxyacridine (water at 20°C)
Add 20 parts of the solubility (approximately 5 g per 100 g), masticate it well with a rubber roll machine, extrude it, and heat it at 200℃ for 2 minutes to form a tube with an outer diameter of 5 mm, an inner diameter of 3 mm, and a length of 350 mm. Created. This was post-vulcanized at 180℃ for 2 days,
Thereafter, a urinary catheter was prepared using a conventional method. The obtained urinary catheter was subjected to the same antibacterial activity test as in Example 1, and the results shown in Table 1 were obtained. Furthermore, when this catheter was actually applied clinically to five patients, no urinary tract infection was observed in any of the patients even after three weeks of indwelling. Furthermore, no obstruction of the urinary tract due to solid matter deposited inside the catheter was observed, and the catheter was removed smoothly without causing any pain to the patient. Example 3 100 parts of dimethylpolysiloxane end-capped with hydroxyl groups, 10 parts of silica airgel, 2 parts of methyltriethoxysilane, dibutyltin dilaurate
After mixing 0.2 parts and 10 parts of readily water-soluble benzyldimethyltetradecylammonium chloride as an antibacterial agent, the mixture was immediately poured into a casting mold and cured at room temperature to produce a tube with an outer diameter of 5 mm, an inner diameter of 3 mm, and a length of 350 mm. did. A urinary catheter was prepared using this in a conventional manner, and an antibacterial activity test was conducted in the same manner as in Example 1. The results shown in Table 1 were obtained. Furthermore, when this catheter was actually applied clinically to five patients, no urinary tract infection was observed in any of the patients even after the catheter was left in the body for two weeks. Furthermore, no obstruction of the urinary tract due to solid matter deposited inside the catheter was observed, and the catheter was removed smoothly without causing any pain to the patient.
【表】
（発明の効果）
以上、実施例から明らかなように、本発明の導
尿カテーテルは抗菌剤の徐放性を有するものであ
るから、長期間の体内留置に伴う***を効果
的に防止し得るものであり、導尿カテーテルとし
て好適に用いられるほか、手術後の患者の体内残
留血液や体液等を排液するためのドレインチユー
ブ等への応用も可能である。[Table] (Effects of the invention) As is clear from the examples above, the urinary catheter of the present invention has a sustained release property of antibacterial agents, so it is effective against urinary tract infections caused by long-term indwelling in the body. In addition to being suitably used as a urinary catheter, it can also be applied to a drain tube for draining blood and body fluids remaining in a patient's body after surgery.
Claims (1)
ーンゴムからなる抗菌剤徐放性導尿カテーテル。 ２ 水溶性のカチオン型抗菌剤が水溶性ビグアニ
ド系化合物又はビグアニド化合物の水溶性の塩で
ある特許請求の範囲第１項記載の抗菌剤徐放性導
尿カテーテル。 ３ 水溶性のカチオン型抗菌剤が水溶性アクリジ
ン系化合物又はアクリジン化合物の水溶性の塩で
ある特許請求の範囲第１項記載の抗菌剤徐放性導
尿カテーテル。 ４ 水溶性のカチオン型抗菌剤が水溶性第４級ア
ンモニウム塩系化合物である特許請客の範囲第１
項記載の抗菌剤徐放性導尿カテーテル。[Scope of Claims] 1. An antibacterial agent sustained release urinary catheter made of silicone rubber containing a water-soluble cationic antibacterial agent. 2. The antibacterial agent sustained release urinary catheter according to claim 1, wherein the water-soluble cationic antibacterial agent is a water-soluble biguanide compound or a water-soluble salt of a biguanide compound. 3. The antibacterial agent sustained release urinary catheter according to claim 1, wherein the water-soluble cationic antibacterial agent is a water-soluble acridine compound or a water-soluble salt of an acridine compound. 4 Scope of the patent applicant where the water-soluble cationic antibacterial agent is a water-soluble quaternary ammonium salt compound No. 1
Antibacterial agent sustained release urinary catheter as described in Section 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58188940A JPS6080457A (en) | 1983-10-07 | 1983-10-07 | Antibacterial agent slow releasing urethral catheter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58188940A JPS6080457A (en) | 1983-10-07 | 1983-10-07 | Antibacterial agent slow releasing urethral catheter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6080457A JPS6080457A (en) | 1985-05-08 |
| JPH0474026B2 true JPH0474026B2 (en) | 1992-11-25 |
Family
ID=16232561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58188940A Granted JPS6080457A (en) | 1983-10-07 | 1983-10-07 | Antibacterial agent slow releasing urethral catheter |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6080457A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102006020644A1 (en) * | 2006-04-28 | 2007-10-31 | Bayer Innovation Gmbh | Silicone elastomer containing homogeneously dispersed, micronized antiseptic, e.g. chlorhexidine, octenidine or triclosan, used for the production of plastic medical articles, especially catheters |
| US8652499B2 (en) | 2008-03-10 | 2014-02-18 | Toray Industries, Inc. | Medical antimicrobial composition and medical device comprising the same |
| US11524015B2 (en) | 2013-03-15 | 2022-12-13 | Brigham Young University | Methods for treating inflammation, autoimmune disorders and pain |
| CN105209465A (en) | 2013-03-15 | 2015-12-30 | 布莱阿姆青年大学 | Methods for treating inflammation, autoimmune disorders and pain |
| US11690855B2 (en) | 2013-10-17 | 2023-07-04 | Brigham Young University | Methods for treating lung infections and inflammation |
| US20150203527A1 (en) | 2014-01-23 | 2015-07-23 | Brigham Young University | Cationic steroidal antimicrobials |
| US10226550B2 (en) | 2016-03-11 | 2019-03-12 | Brigham Young University | Cationic steroidal antimicrobial compositions for the treatment of dermal tissue |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59228856A (en) * | 1983-06-10 | 1984-12-22 | ユニチカ株式会社 | Anti-bacterial agent slow releasing urination catheter |
| JPS6040061A (en) * | 1983-08-12 | 1985-03-02 | ユニチカ株式会社 | Antibacterial agent slow releasing urine guide catheter |
-
1983
- 1983-10-07 JP JP58188940A patent/JPS6080457A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59228856A (en) * | 1983-06-10 | 1984-12-22 | ユニチカ株式会社 | Anti-bacterial agent slow releasing urination catheter |
| JPS6040061A (en) * | 1983-08-12 | 1985-03-02 | ユニチカ株式会社 | Antibacterial agent slow releasing urine guide catheter |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6080457A (en) | 1985-05-08 |
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