JPH0310341B2 - - Google Patents
Info
- Publication number
- JPH0310341B2 JPH0310341B2 JP58145429A JP14542983A JPH0310341B2 JP H0310341 B2 JPH0310341 B2 JP H0310341B2 JP 58145429 A JP58145429 A JP 58145429A JP 14542983 A JP14542983 A JP 14542983A JP H0310341 B2 JPH0310341 B2 JP H0310341B2
- Authority
- JP
- Japan
- Prior art keywords
- urinary catheter
- acid
- biguanide compound
- compound
- antibacterial
- 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
- 230000002485 urinary effect Effects 0.000 claims description 39
- -1 biguanide compound Chemical class 0.000 claims description 36
- 230000000844 anti-bacterial effect Effects 0.000 claims description 30
- 229940123208 Biguanide Drugs 0.000 claims description 28
- 239000000126 substance Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- 238000013268 sustained release Methods 0.000 claims description 8
- 239000012730 sustained-release form Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000000243 solution Substances 0.000 description 20
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 210000002700 urine Anatomy 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 238000007654 immersion Methods 0.000 description 6
- 229920005862 polyol Polymers 0.000 description 6
- 150000003077 polyols Chemical class 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 244000043261 Hevea brasiliensis Species 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000004283 biguanides Chemical class 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229920003052 natural elastomer Polymers 0.000 description 4
- 229920001194 natural rubber Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 208000019206 urinary tract infection Diseases 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 3
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229960003260 chlorhexidine Drugs 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000007598 dipping method Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 239000004800 polyvinyl chloride Substances 0.000 description 3
- 229920000915 polyvinyl chloride Polymers 0.000 description 3
- 210000001635 urinary tract Anatomy 0.000 description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- KUDUQBURMYMBIJ-UHFFFAOYSA-N 2-prop-2-enoyloxyethyl prop-2-enoate Chemical compound C=CC(=O)OCCOC(=O)C=C KUDUQBURMYMBIJ-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- IRIAEXORFWYRCZ-UHFFFAOYSA-N Butylbenzyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCC1=CC=CC=C1 IRIAEXORFWYRCZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- BJQHLKABXJIVAM-UHFFFAOYSA-N Diethylhexyl phthalate Natural products CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000011247 coating layer Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000000645 desinfectant Substances 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- 229920001519 homopolymer Polymers 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920001228 polyisocyanate Polymers 0.000 description 2
- 239000005056 polyisocyanate Substances 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000004945 silicone rubber Substances 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229920003051 synthetic elastomer Polymers 0.000 description 2
- 239000005061 synthetic rubber Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 238000004073 vulcanization Methods 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- PMJHHCWVYXUKFD-SNAWJCMRSA-N (E)-1,3-pentadiene Chemical compound C\C=C\C=C PMJHHCWVYXUKFD-SNAWJCMRSA-N 0.000 description 1
- MTZUIIAIAKMWLI-UHFFFAOYSA-N 1,2-diisocyanatobenzene Chemical compound O=C=NC1=CC=CC=C1N=C=O MTZUIIAIAKMWLI-UHFFFAOYSA-N 0.000 description 1
- ZTNJGMFHJYGMDR-UHFFFAOYSA-N 1,2-diisocyanatoethane Chemical compound O=C=NCCN=C=O ZTNJGMFHJYGMDR-UHFFFAOYSA-N 0.000 description 1
- ZXHZWRZAWJVPIC-UHFFFAOYSA-N 1,2-diisocyanatonaphthalene Chemical compound C1=CC=CC2=C(N=C=O)C(N=C=O)=CC=C21 ZXHZWRZAWJVPIC-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- BAZVBVCLLGYUFS-UHFFFAOYSA-N 1-o-butyl 2-o-dodecyl benzene-1,2-dicarboxylate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC BAZVBVCLLGYUFS-UHFFFAOYSA-N 0.000 description 1
- OEPOKWHJYJXUGD-UHFFFAOYSA-N 2-(3-phenylmethoxyphenyl)-1,3-thiazole-4-carbaldehyde Chemical compound O=CC1=CSC(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=N1 OEPOKWHJYJXUGD-UHFFFAOYSA-N 0.000 description 1
- JGIZWNFPEUFBOA-UHFFFAOYSA-N 2-(6,6-diaminohexyl)-1-(diaminomethylidene)guanidine Chemical compound NC(N)CCCCCNC(=N)NC(N)=N JGIZWNFPEUFBOA-UHFFFAOYSA-N 0.000 description 1
- YEVQZPWSVWZAOB-UHFFFAOYSA-N 2-(bromomethyl)-1-iodo-4-(trifluoromethyl)benzene Chemical class FC(F)(F)C1=CC=C(I)C(CBr)=C1 YEVQZPWSVWZAOB-UHFFFAOYSA-N 0.000 description 1
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- VHSHLMUCYSAUQU-UHFFFAOYSA-N 2-hydroxypropyl methacrylate Chemical compound CC(O)COC(=O)C(C)=C VHSHLMUCYSAUQU-UHFFFAOYSA-N 0.000 description 1
- GWZMWHWAWHPNHN-UHFFFAOYSA-N 2-hydroxypropyl prop-2-enoate Chemical compound CC(O)COC(=O)C=C GWZMWHWAWHPNHN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- KBXUTBMGSKKPFL-UHFFFAOYSA-N 3-hydroxy-2-methylprop-2-enoic acid Chemical compound OC=C(C)C(O)=O KBXUTBMGSKKPFL-UHFFFAOYSA-N 0.000 description 1
- QZPSOSOOLFHYRR-UHFFFAOYSA-N 3-hydroxypropyl prop-2-enoate Chemical compound OCCCOC(=O)C=C QZPSOSOOLFHYRR-UHFFFAOYSA-N 0.000 description 1
- UPMLOUAZCHDJJD-UHFFFAOYSA-N 4,4'-Diphenylmethane Diisocyanate Chemical compound C1=CC(N=C=O)=CC=C1CC1=CC=C(N=C=O)C=C1 UPMLOUAZCHDJJD-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- GOJCZVPJCKEBQV-UHFFFAOYSA-N Butyl phthalyl butylglycolate Chemical compound CCCCOC(=O)COC(=O)C1=CC=CC=C1C(=O)OCCCC GOJCZVPJCKEBQV-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 244000286663 Ficus elastica Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-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
- JCELWOGDGMAGGN-UHFFFAOYSA-N N=C=O.N=C=O.C1=CC=CC=C1C(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound N=C=O.N=C=O.C1=CC=CC=C1C(C=1C=CC=CC=1)C1=CC=CC=C1 JCELWOGDGMAGGN-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- YSMRWXYRXBRSND-UHFFFAOYSA-N TOTP Chemical compound CC1=CC=CC=C1OP(=O)(OC=1C(=CC=CC=1)C)OC1=CC=CC=C1C YSMRWXYRXBRSND-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 125000005250 alkyl acrylate group Chemical group 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- ZFMQKOWCDKKBIF-UHFFFAOYSA-N bis(3,5-difluorophenyl)phosphane Chemical compound FC1=CC(F)=CC(PC=2C=C(F)C=C(F)C=2)=C1 ZFMQKOWCDKKBIF-UHFFFAOYSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- BEWFIPLBFJGWSR-UHFFFAOYSA-N butyl 12-acetyloxyoctadec-9-enoate Chemical compound CCCCCCC(OC(C)=O)CC=CCCCCCCCC(=O)OCCCC BEWFIPLBFJGWSR-UHFFFAOYSA-N 0.000 description 1
- BNMJSBUIDQYHIN-UHFFFAOYSA-N butyl dihydrogen phosphate Chemical class CCCCOP(O)(O)=O BNMJSBUIDQYHIN-UHFFFAOYSA-N 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000004359 castor oil Chemical class 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 1
- YACLQRRMGMJLJV-UHFFFAOYSA-N chloroprene Chemical compound ClC(=C)C=C YACLQRRMGMJLJV-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- PDXRQENMIVHKPI-UHFFFAOYSA-N cyclohexane-1,1-diol Chemical compound OC1(O)CCCCC1 PDXRQENMIVHKPI-UHFFFAOYSA-N 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- PUFGCEQWYLJYNJ-UHFFFAOYSA-N didodecyl benzene-1,2-dicarboxylate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCCCCCC PUFGCEQWYLJYNJ-UHFFFAOYSA-N 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- MIMDHDXOBDPUQW-UHFFFAOYSA-N dioctyl decanedioate Chemical compound CCCCCCCCOC(=O)CCCCCCCCC(=O)OCCCCCCCC MIMDHDXOBDPUQW-UHFFFAOYSA-N 0.000 description 1
- XWVQUJDBOICHGH-UHFFFAOYSA-N dioctyl nonanedioate Chemical compound CCCCCCCCOC(=O)CCCCCCCC(=O)OCCCCCCCC XWVQUJDBOICHGH-UHFFFAOYSA-N 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- MQRJBSHKWOFOGF-UHFFFAOYSA-L disodium;carbonate;hydrate Chemical compound O.[Na+].[Na+].[O-]C([O-])=O MQRJBSHKWOFOGF-UHFFFAOYSA-L 0.000 description 1
- LHGJTWLUIMCSNN-UHFFFAOYSA-L disodium;sulfate;heptahydrate Chemical compound O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O LHGJTWLUIMCSNN-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 208000005053 encephalomalacia Diseases 0.000 description 1
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000003203 everyday effect Effects 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
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Chemical class CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- GEAWFZNTIFJMHR-UHFFFAOYSA-N hepta-1,6-diene Chemical compound C=CCCCC=C GEAWFZNTIFJMHR-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 150000002483 hydrogen compounds Chemical class 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000011256 inorganic filler Substances 0.000 description 1
- 229910003475 inorganic filler Inorganic materials 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- LADVLFVCTCHOAI-UHFFFAOYSA-N isocyanic acid;toluene Chemical compound N=C=O.CC1=CC=CC=C1 LADVLFVCTCHOAI-UHFFFAOYSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- DJDSLBVSSOQSLW-UHFFFAOYSA-N mono(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(O)=O DJDSLBVSSOQSLW-UHFFFAOYSA-N 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- WFKDPJRCBCBQNT-UHFFFAOYSA-N n,2-dimethylprop-2-enamide Chemical compound CNC(=O)C(C)=C WFKDPJRCBCBQNT-UHFFFAOYSA-N 0.000 description 1
- YRVUCYWJQFRCOB-UHFFFAOYSA-N n-butylprop-2-enamide Chemical compound CCCCNC(=O)C=C YRVUCYWJQFRCOB-UHFFFAOYSA-N 0.000 description 1
- ZIWDVJPPVMGJGR-UHFFFAOYSA-N n-ethyl-2-methylprop-2-enamide Chemical compound CCNC(=O)C(C)=C ZIWDVJPPVMGJGR-UHFFFAOYSA-N 0.000 description 1
- SWPMNMYLORDLJE-UHFFFAOYSA-N n-ethylprop-2-enamide Chemical compound CCNC(=O)C=C SWPMNMYLORDLJE-UHFFFAOYSA-N 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- PMJHHCWVYXUKFD-UHFFFAOYSA-N piperylene Natural products CC=CC=C PMJHHCWVYXUKFD-UHFFFAOYSA-N 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920006295 polythiol Polymers 0.000 description 1
- BPJZKLBPJBMLQG-KWRJMZDGSA-N propanoyl (z,12r)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OC(=O)CC BPJZKLBPJBMLQG-KWRJMZDGSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 201000004537 pyelitis Diseases 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229940076133 sodium carbonate monohydrate Drugs 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- DVKJHBMWWAPEIU-UHFFFAOYSA-N toluene 2,4-diisocyanate Chemical compound CC1=CC=C(N=C=O)C=C1N=C=O DVKJHBMWWAPEIU-UHFFFAOYSA-N 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 208000000143 urethritis Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
- Materials For Medical Uses (AREA)
Description
本発明は、導尿カテーテルの製造方法に関する
ものであり、さらに詳しくは抗菌物質徐放性能を
有する導尿カテーテルの製造方法に関するもので
ある。
脊髄損傷、脳出血、脳軟化症、手術後の患者に
おいては排尿困難、尿失禁などの症状を伴うこと
が多い。このような場合は円滑な尿路を確保し、
その結果、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
ルを用いた導尿法が採用される。この際に用いら
れるカテーテルは特に導尿カテーテルと称され
る。
導尿法は排尿を速やかに行わせるといつた極め
て有用な治療手段であるため泌尿器科のみならず
外科、内科、産婦人科などの領域で日常的に繁用
されているが、一方では、いつたん導尿カテーテ
ルが尿路に留置されると感染の発生は避け難いと
いう問題がある。すなわち、導尿カテーテルは長
時間尿路に留置しておくものであるから、このカ
テーテルを通じて細菌が侵入し、尿道炎、膀胱
炎、腎う炎などの症状が頻発する。従来から多用
されている開放持続導尿法(硝子瓶など滅菌され
ていない容器に集尿する方法)を施行した場合に
は、3日以内に42〜80%の症例に感染が発生し、
7日目には全例に感染が成立したことが報告され
ている。
このため、尿路感染防止に関しては膀胱の洗浄
や殺菌剤の注入などの方法が行われているが、操
作が面倒であり、またこの操作を行うこと自体が
新たな感染源となるといつた不都合な面が多い。
また、抗菌物質の予防的投与などの化学療法も
行われているが、大量投与もしくは抗菌物質の種
類によつては少量にても頻発する副作用の問題及
びいつたん感染が生じると菌交代症が発現しやす
いことなどの問題から無計画な化学療法はむしろ
有害であると言われる程に、抗菌物質に関しては
局所的利用が強く望まれている。
抗菌物質の局所的利用に関しては、導尿カテー
テルの内壁面及び/又は外壁面にポリビニルアル
コール系樹脂又はポリ−2−ヒドロキシエチルメ
タクリレート系樹脂などの親水性樹脂からなる被
覆層を形成させ、この層に抗菌物質を含ませた導
尿カテーテルが知られている。しかし、これらの
場合、抗菌物質は水溶性であつて単に親水性樹脂
層内に吸着しているだけであるから、使用に際し
て抗菌物質は尿中に拡散し、速やかに体外へ留出
してしまう結果、抗菌物質を長期にわたり、適切
な濃度で尿中へ徐放できないという欠点があつ
た。
本発明者らは、このような現況に鑑み、体内留
置期間中において尿路感染防止のために抗菌物質
を適切な速度で徐放しうる導尿カテーテルを簡便
に製造する方法を確立することを目的として鋭意
研究を重ねた結果、導尿カテーテルに特定の抗菌
物質を吸収させ、この抗菌物質を水難溶性化合物
に変えることにより抗菌物質が長期にわたり尿中
へ徐放され、尿路感染防止にために好ましい特性
を有する導尿カテーテルが得られることを見い出
し、本発明に到達したものである。
すなわち本発明は、ビグアニド化合物を含有す
る溶液を導尿カテーテルに吸収させ、しかるのち
導尿カテーテルに吸収させたビグアニド化合物を
水難溶性化合物に変えることを特徴とする抗菌物
質徐放性導尿カテーテルの製造方法である。
本発明におけるビグアニド化合物とは下記の一
般式()又は()で示されるものである。
The present invention relates to a method for manufacturing a urinary catheter, and more particularly to a method for manufacturing a urinary catheter having sustained release performance of antibacterial substances. 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, ensure a smooth urinary tract,
As a result, urinary catheterization using a urinary catheter is adopted to promote maintenance or improvement of renal function or to prevent urine leakage. The catheter used in this case is particularly called a urinary catheter. Urinary catheterization is an extremely useful treatment method that allows rapid urination, and is therefore frequently used not only in urology but also in fields such as surgery, internal medicine, obstetrics and gynecology, etc. However, on the other hand, There is a problem in that once a urinary catheter is placed in the urinary tract, the occurrence of infection is unavoidable. That is, since the urinary catheter is left in the urinary tract for a long period of time, bacteria can enter through the catheter, and symptoms such as urethritis, cystitis, and pyelitis frequently occur. When the conventional open continuous catheterization method (a method of collecting urine in an unsterilized container such as a glass bottle) was performed, infection occurred in 42-80% of cases within 3 days.
It has been reported that infection was established in all cases on the seventh day. For this reason, methods such as cleaning the bladder and injecting disinfectants have been used to prevent urinary tract infections, but they are cumbersome to operate and are inconvenient as they can become a source of new infections. There are many aspects. Chemotherapy, such as the prophylactic administration of antibacterial substances, is also used, but with large doses or depending on the type of antibacterial substance, there are problems with frequent side effects even with small doses, and bacterial replacement occurs once an infection occurs. There is a strong desire for local use of antibacterial substances, to the extent that unplanned chemotherapy is said to be harmful due to problems such as the ease with which antibiotics can develop. For local use of antibacterial substances, a coating layer made of a hydrophilic resin such as polyvinyl alcohol resin or poly-2-hydroxyethyl methacrylate resin is formed on the inner and/or outer wall surfaces of the urinary catheter. Urinary catheters containing antibacterial substances are known. However, in these cases, the antibacterial substance is water-soluble and simply adsorbed within the hydrophilic resin layer, so when used, the antibacterial substance diffuses into the urine and is quickly distilled out of the body. However, the drawback was that antibacterial substances could not be released into the urine at an appropriate concentration over a long period of time. In view of the current situation, the present inventors aimed to establish a method for easily manufacturing a urinary catheter that can sustainably release an antibacterial substance at an appropriate rate to prevent urinary tract infection during the period of indwelling in the body. As a result of intensive research, we have found that by absorbing a specific antibacterial substance into a urinary catheter and converting this antibacterial substance into a poorly water-soluble compound, the antibacterial substance is released into the urine slowly over a long period of time, which can help prevent urinary tract infections. The inventors have discovered that a urinary catheter having favorable characteristics can be obtained, and have arrived at the present invention. That is, the present invention provides an antibacterial substance sustained release urinary catheter characterized in that a solution containing a biguanide compound is absorbed into a urinary catheter, and then the biguanide compound absorbed into the urinary catheter is converted into a poorly water-soluble compound. This is the manufacturing method. The biguanide compound in the present invention is represented by the following general formula () or ().
【式】【formula】
【式】
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
ニトリル基等であり、R′は水素又はアルキル基
である。なおnは正の整数であるが2〜10の範囲
が好適である。かかるビグアニド化合物の好適な
具体的な例をあげれば1,6−ジ−(4−クロロ
フエニルビグアニド)ヘキサン、ジアミノヘキシ
ルビグアニド、1,6−ジ−(アミノヘキシルビ
グアニド)ヘキサン等である。なかでも、1,6
−ジ−(4−クロロフエニルビグアニド)ヘキサ
ン(別名クロルヘキシジン)は広範囲の微生物に
対し強力な殺菌力を有し、かつ人体に対する毒性
も低いところから、今日医療、衛生並びに食品業
界において最も広く使用されている殺菌消毒剤の
一つであり、本発明においても特に好ましく用い
られる。すなわち、クロルヘキシジンは種々の抗
菌物質の中でもグラム陽性球菌やグラム陰性桿菌
などに広範囲にわたつて低濃度で抗菌作用を示す
ことが知られており、手指、皮膚、粘膜面の消毒
や医療器具の消毒に広く用いられている抗菌物質
である。本発明においてビグアニド化合物を含む
溶液としては、溶液中のビグアニド化合物の濃度
が5重量%以上、特に10重量%以上含まれている
ものが好ましく用いられる。好ましい溶液として
は、例えばビグアニド化合物の水溶液あるいはビ
グアニド化合物を水とテトラヒドロフランの混合
溶液に溶解した溶液があげられるが、特に水−テ
トラヒドロフラン、水−ジオキサンのような水
と、水と混合し、かつ導尿カテーテルを膨潤しう
るような有機溶媒の一種又は2種以上とからなる
混合液にビグアニド化合物を溶解した溶液が好ま
しい。また、本発明に用いられるビグアニド化合
物を含む溶液は、ビグアニド化合物の抗菌活性を
損わない程度にアニオン性界面活性剤又は非イオ
ン性界面活性剤を含んでいても何らさしつかえな
い。
本発明において用いられる導尿カテーテルとし
ては、例えば天然ゴム、合成ゴム、シリコンゴ
ム、ポリウレタン、軟質ポリ塩化ビニル等を素材
とし、浸漬法、射出法などの方法で成形されたも
のがあげられる。ここで天然ゴムとは、ゴム植物
の樹皮に切付を行つた時に流れ出る種々の有機物
及び無機物を含有した水溶液を分散媒体とし、ゴ
ム分を分散質とし、必要に応じてPH調整剤、加硫
剤、加硫促進剤、軟化剤、充填剤、老化防止剤等
を配合したラテツクスに凝固、加硫等の操作を行
つて得られたものを意味する。合成ゴムとして
は、例えばブタジエン、イソプレン、1,3−ペ
ンタジエン、1.5−ヘキサジエン、1,6−ヘプ
タジエン、クロロプレン等のジエン系モノマーの
単一重合体あるいはその共重合体あるいはその共
重合体があげられる。シリコンゴムとは高重合度
のオルガノポリシロキサンに、必要に応じて、例
えば無機充填剤、分散促進剤、加硫剤等を配合し
たものを意味し、オルガノポリシロキサンとして
は、例えば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あ
げられる。また、ポリウレタンとは主鎖の繰り返
し単位中にポリイソシアナートとポリオールから
なるウレタン結合を有するエラストマーを意味す
る。ポリイソシアナートとしては、例えばトルエ
ンジイソシアナート、キシレンジイソシアナー
ト、ナフタレンジイソシアナート、ジフエニルメ
タンジイソシアナート、フエニレンジイソシアナ
ート、エチレンジイソシアナート、シクロヘキシ
レンジイソシアナート、トリフエニルメタントリ
イソシアナート、トルエントリイソシアナート等
があげられ、ポリオールとしては、例えばエチレ
ングリコール、プロピレングリコール、ブチレン
グリコール、ジエチレングリコール、シクロヘキ
サンジオール、ペンタエリスリトール、グリセリ
ン、1,1,1−トリメチロールプロパン等のポ
リオール、ポリエチレングリコール、ポリプロピ
レイングリコール、ポリテトラメチレングリコー
ル、ポリエチレングリコール/ポリプロピレング
リコール共重合体等のポリエーテルポリオール等
があげられる。また、ポリオールには、例えばコ
ハク酸、グルタル酸、アジピン酸、セバシン酸、
イソフタル酸、フタル酸、テレフタル酸等のジカ
ルボン酸とエチレングリコールやプロピレングリ
コール等の縮合によつて得られる両末端に水酸気
を有するポリエステル等も含まれる。さらに、こ
れらのポリオールの一部をポリアミン、ポリチオ
ール、ポリカルボン酸等の他の活性水素化合物に
置き換えたものも含まれる。また、軟質ポリ塩化
ビニルとしては、例えばポリ塩化ビニル単独重合
体に可塑剤を配合したものあるいは他成分との共
重合により内部可塑化したものがあげられる。前
者の可塑剤としては、ジブチルフタレート、ジ−
2−エチルヘキシルフタレート、ジオクチルフタ
レート、ブチルラウリルフタレート、ジラウリル
フタレート、ブチルベンジルフタレート等のフタ
ル酸エステル類、ジオクチルアジペート、ジオク
チルアゼレート、ジオクチルセバケート等の直鎖
二塩基酸エステル類、トリクレジルホスフエー
ト、トリキシレニルホスフエート、モノブチル−
ジキシレニルホスフエート、トリオクチルホスフ
エート等のリン酸エステル類、メチルアセチルリ
シノレート、ブチルアセチルリシノレート等のヒ
マシ油誘導体、大豆油等の不飽和脂肪酸をエポキ
シ化したエポキシ化植物油、炭素数6〜10の脂肪
酸のトリ又はテトラエチレンフグリコールエステ
ル、ブチルフタリルブチルグリコレート等のエチ
レングリコール誘導体、平均分子量、1000〜3000
の粘調な低級ポリエステル系可塑剤等があげられ
る。また、後者の塩化ヒニルの共重合モノマーと
しては、例えば酢酸ビニル、塩化ビニリデン、ア
クリル酸又はメタクリル酸及びそのエステル、マ
レイン酸とそのエステル、アクリロニトリル等が
あげられる。
また、本発明においては導尿カテーテルとし
て、上記のごとき導尿カテーテルの内壁面及び/
又は外壁面に親水性樹脂を被覆したものも使用で
きる。導尿カテーテルに親水性樹脂を被覆させる
方法としては、例えば親水性樹脂溶液を用いる浸
漬法、はけ塗り法あるいは吹き付け法、親水性単
量体又はその部分重合体の溶液に導尿カテーテル
を浸漬し、引き上げた後、紫外線重合、放射線重
合あるいはラジカル開始剤によるラジカル重合を
行う方法がある。親水性単量体としては、例え
ば、2−ヒドロキシエチルアクリレート、2−ヒ
ドロキシエチルメタクリレート、2−ヒドロキシ
プロピルアクリレート、2−ヒドロキシプロピル
メタクリレート、3−ヒドロキシプロピルアクリ
レート、3−ヒドロキシメタクリレートなどのヒ
ドロキシ低級アルキルアクリレート又はメタクリ
レート、アクリルアミド、メタクリアミド、N−
メチルアクリルアミド、N−メチルメタクリルア
ミド、N−エチルアクリルアミド、N−エチルメ
タクリルアミド、N−イソプロピルアクリルアミ
ド、N−ブチルアクリルアミドなど一般式
(R1は水素又は炭素数1〜4のアルキル基、R2、
R3は水素又はアルキル基である。)で示される化
合物、アクリル酸、メタクリル酸、マレイン酸あ
るいはこれらの酸塩などの化合物、さらにN−ビ
ニルピロリドンなどのN−ビニル化合物などがあ
げられる。また、上記被覆層の強靭さを増すため
に架橋剤としてエチレングリコールジアクリレー
ト、エチレングリコールジメタクリレートなどの
ジビニル化合物を用いることも可能である。ま
た、親水性樹脂としては、上記単量体の少なくと
も1種を主成分とする重合体又は共重合体、ポリ
カルボン酸とポリエチレンオキサイド又はポリビ
ニルアルコールとからなる化合物、ポリビニルア
ルコール、エチレン−酢酸ビニル共重合体のけん
化物などがあげられる。
本発明の方法によつて抗菌物質徐放性導尿カテ
ーテルを製造するには、まず導尿カテーテルにビ
グアニド化合物を含む溶液を吸収させる。このた
めには、例えばビグアニド化合物を含む溶液中に
導尿カテーテルを浸漬するのが最も簡便な方法で
ある。この場合、ビグアニド化合物を含む溶液の
温度はビグアニド化合物の抗菌活性又は導尿カテ
ーテルの材質に著しい悪影響を及ぼさないような
温度であればどのような温度であつてもよいが、
10〜150℃、特に室温〜80℃が好ましい。好まし
い浸漬時間は浸漬温度によつても異なるが、通常
5分〜1週間、特に10分〜4日間程度が好まし
い。
本発明においては、しかるのち導尿カテーテル
に吸収させたビグアニド化合物を水難溶性化合物
に変えることが必要である。ここにいう水難溶性
とは、化合物の20℃における100gの蒸溜水に対
する溶解度が0.001〜3.0g、好ましくは0.005g〜
2.0gの範囲のものを指す。水に対する溶解度が
0.001g未満では局所での放出量が低く、殺菌剤
としての効力が減退する。一方、3.0gをこえる
ものでは尿中への抗菌物質の拡散が速く、長期に
わたり抗菌剤を徐放することができない。
ビグアニド化合物の水難溶性化合物としては、
ビグアニド化合物自体及びその塩酸塩、臭化水素
酸塩、硝酸塩、リン酸塩、硫酸塩、ホウ酸塩、炭
酸塩、重炭酸塩、安息香酸塩、ギ酸塩、酒石酸
塩、酢酸塩など種々の酸塩があげられる。
導尿カテーテルに吸収させたビグアニド化合物
を水難溶性化合物に変えるには、例えばビグアニ
ド化合物を吸収させた導尿カテーテルを塩酸、臭
化水素酸、硝酸、リン酸、硫酸、ホウ酸、炭酸、
重炭酸、安息香酸、ギ酸、酒石酸、酢酸などの溶
液又は上記酸の陰イオンを含む溶液又はカルシウ
ムイオン、マグネシウムイオンなどの多価金属イ
オンを含む溶液又はこれら二種以上の系からなる
混合溶液に浸漬することにより行うことができ
る。また、導尿カテーテルに上記酸の陰イオンを
含む塩をあらかじめ吸収させておいたのち、この
カテーテルをビグアニド化合物を含む溶液に浸漬
することにより、導尿カテーテルに吸収されたビ
グアニド化合物を水難溶性化合物に変えることも
できる。浸漬に際しての溶液のPH、温度はビグア
ニド化合物の抗菌性又は導尿カテーテルの材質に
著しい悪影響を及ぼさないような条件であればど
のような条件であつてもよいが、0〜100℃、特
に10〜80℃が好ましい。好ましい浸漬時間は浸漬
温度によつても異なるが通常1時間〜1週間、特
に2時間〜48時間程度が好ましい。
本発明においては、これらの処理後、必要であ
れば10〜80℃、好ましくは30〜70℃の範囲で導尿
カテーテルを乾燥してもよい。
ビグアニド化合物は種々の酸と塩を形成する
が、形成した塩の水への溶解度は、使用した酸の
種類により大きく変化し、水難溶性の塩を形成し
たときにはその溶液の抗菌活性が低下する可能性
がある。しかしながら、一般に膀胱洗浄に使われ
るクロルヘキシジングルコン酸塩の濃度は0.02
(W/V)%の濃度とかなり低いものであり、ま
た畑田昭雄ら、月刊薬事、15、2193(1973)によ
れば尿路感染の起因菌となるPseudomonas
aeruginosa、Proteus vulgaris、Escherichia
coli、Staphylococcus aureusに対するクロルヘ
キシジンの菌発育最小阻止濃度(MIC)は各々
10、12.5、1.25、1.0μg/mlであることから、水
難溶性のビグアニド化合物の溶解度が0.001g程
度であつても十分に抗菌活性を有する。
このように、水難溶性のビグアニド化合物は酸
塩の種類により溶解度が異なるので、本発明によ
ればビグアニド化合物を水難溶性化合物に変える
際の酸又は陰イオン又は多価金属イオンの種類を
種々選択してビグアニド化合物の溶解度を変える
ことにより、導尿カテーテルから尿中へ徐放する
抗菌物質の速度を任意に調製することが可能であ
る。
以上述べた一連の操作を行つた結果、導尿カテ
ーテルに保持された水難溶性のビグアニド化合物
の量が少ないときには、所望量に達するまで一連
の操作を繰り返せばよい。
以上のように本発明の製造方法によれば、従来
より簡便な方法で必要に応じた徐放速度及び徐放
期間をもつ抗菌物質徐放性導尿カテーテルを製造
することができる。
以下実施例をあげて本発明をさらに具体的に説
明する。なお実施例中の「部」は「重量部」を意
味する。
実施例 1
天然ゴム製フオーリーバルーンカテーテル(恒
産商事)を、クロルヘキシジルグルコン酸塩50部
を蒸留水50部に溶解した溶液に室温下に72時間浸
漬したのち、50℃で乾燥した。乾燥後のカテーテ
ルを塩化ナトリウム10部及び蒸留水90部からなる
水溶液に室温下で10時間浸漬したのち、50℃で乾
燥した。
実施例 2
塩化ナトリウム10部を硫酸ナトリウム・7水塩
10部に変えた以外は実施例1と同様の操作を行つ
た。
実施例 3
塩化ナトリウム10部を炭酸ナトリウム・1水塩
10部に変えた以外は実施例1と同様の操作を行つ
た。
実施例 4
塩化ナトリウム10部を硝酸ナトリウム10部に変
えた以外は実施例1と同様の操作を行つた。
実施例 5
実施例1の操作を2回繰り返した。
比較例 1
天然ゴム製フオーリーバルーンカテーテル(恒
産商事)をクロルヘキシジルグルコン酸塩50部及
び蒸留水50部からなる溶液に室温下に72時間浸漬
したのち50℃で乾燥した。
以上の実施例1〜5及び比較例1で得られたカ
テーテルを、各々37℃の試験尿中に浸漬し、
Bacillus subtilis ATCC6633を検定菌として円
筒平板法(ペーパーデイスク法)にて各尿の抗菌
活性テストを行つた。試験尿を毎日新しい試験尿
に取り替えて同様の抗菌活性テストを繰り返して
行つた。結果を表1に示す1[Formula] Here, R is an alkyl group, an aminoalkyl group, 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. , R' is hydrogen or an alkyl group. Note that n is a positive integer, preferably in the range of 2 to 10. Preferred specific examples of such biguanide compounds include 1,6-di-(4-chlorophenylbiguanide)hexane, diaminohexylbiguanide, and 1,6-di(aminohexylbiguanide)hexane. Among them, 1,6
-Di-(4-chlorophenylbiguanide)hexane (also known as chlorhexidine) has strong bactericidal activity against a wide range of microorganisms and has low toxicity to the human body, so it is most widely used today in medicine, hygiene, and the food industry. It is one of the sterilizing and disinfecting agents, and is particularly preferably used in the present invention. In other words, among various antibacterial substances, chlorhexidine is known to exhibit antibacterial activity against Gram-positive cocci and Gram-negative bacilli over a wide range at low concentrations, and is useful for disinfecting hands, skin, mucous membranes, and medical instruments. It is an antibacterial substance widely used in In the present invention, as a solution containing a biguanide compound, a solution containing a biguanide compound in a concentration of 5% by weight or more, particularly 10% by weight or more is preferably used. Preferred solutions include, for example, an aqueous solution of a biguanide compound or a solution of a biguanide compound dissolved in a mixed solution of water and tetrahydrofuran. A solution in which a biguanide compound is dissolved in a mixed liquid consisting of one or more organic solvents that can swell the urinary catheter is preferred. Further, the solution containing the biguanide compound used in the present invention may contain an anionic surfactant or a nonionic surfactant to the extent that the antibacterial activity of the biguanide compound is not impaired. Examples of the urinary catheter used in the present invention include those made of natural rubber, synthetic rubber, silicone rubber, polyurethane, soft polyvinyl chloride, etc., and molded by a method such as a dipping method or an injection method. Natural rubber here refers to an aqueous solution containing various organic and inorganic substances that flows out when the bark of a rubber plant is incised, and the rubber component is used as a dispersoid. It refers to the product obtained by performing operations such as coagulation and vulcanization on a latex containing additives, vulcanization accelerators, softeners, fillers, anti-aging agents, etc. Examples of the synthetic rubber include homopolymers of diene monomers such as butadiene, isoprene, 1,3-pentadiene, 1.5-hexadiene, 1,6-heptadiene, and chloroprene, copolymers thereof, and copolymers thereof. Silicone rubber refers to organopolysiloxane with a high degree of polymerization mixed with, for example, an inorganic filler, a dispersion accelerator, a vulcanizing agent, etc. as necessary. Examples of organopolysiloxane include dimethylpolysiloxane, Examples include methylphenylpolysiloxane, methylvinylpolysiloxane, and fluoroalkylmethylpolysiloxane. Moreover, polyurethane means an elastomer having urethane bonds made of polyisocyanate and polyol in the repeating unit of the main chain. Examples of the polyisocyanate include toluene diisocyanate, xylene diisocyanate, naphthalene diisocyanate, diphenylmethane diisocyanate, phenylene diisocyanate, ethylene diisocyanate, cyclohexylene diisocyanate, and triphenylmethane diisocyanate. Isocyanate, toluene isocyanate, etc., and examples of polyols include polyols such as ethylene glycol, propylene glycol, butylene glycol, diethylene glycol, cyclohexanediol, pentaerythritol, glycerin, 1,1,1-trimethylolpropane, and polyethylene. Examples include polyether polyols such as glycol, polypropylene glycol, polytetramethylene glycol, and polyethylene glycol/polypropylene glycol copolymers. In addition, polyols include, for example, succinic acid, glutaric acid, adipic acid, sebacic acid,
Also included are polyesters having hydroxyl gas at both ends obtained by condensation of dicarboxylic acids such as isophthalic acid, phthalic acid, and terephthalic acid with ethylene glycol, propylene glycol, and the like. Furthermore, those in which a part of these polyols are replaced with other active hydrogen compounds such as polyamines, polythiols, and polycarboxylic acids are also included. Examples of soft polyvinyl chloride include polyvinyl chloride homopolymer blended with a plasticizer or internally plasticized by copolymerization with other components. Examples of the former plasticizer include dibutyl phthalate and di-
Phthalate esters such as 2-ethylhexyl phthalate, dioctyl phthalate, butyl lauryl phthalate, dilauryl phthalate, butyl benzyl phthalate, linear dibasic acid esters such as dioctyl adipate, dioctyl azelate, dioctyl sebacate, tricresyl phosph ate, tricylenyl phosphate, monobutyl-
Phosphate esters such as dixylenyl phosphate and trioctyl phosphate, castor oil derivatives such as methyl acetyl ricinoleate and butyl acetyl ricinoleate, epoxidized vegetable oils obtained by epoxidizing unsaturated fatty acids such as soybean oil, and 6 carbon atoms. Ethylene glycol derivatives such as tri- or tetraethylene fuglycol esters of ~10 fatty acids, butylphthalyl butyl glycolate, average molecular weight, 1000-3000
Examples include viscous lower polyester plasticizers. Examples of the latter copolymerized monomer of hinyl chloride include vinyl acetate, vinylidene chloride, acrylic acid or methacrylic acid and its ester, maleic acid and its ester, acrylonitrile, and the like. In addition, in the present invention, as a urinary catheter, the inner wall surface of the urinary catheter as described above and/or
Alternatively, a material whose outer wall surface is coated with a hydrophilic resin can also be used. Examples of methods for coating a urinary catheter with a hydrophilic resin include dipping, brushing, or spraying using a hydrophilic resin solution, and dipping the urinary catheter in a solution of a hydrophilic monomer or a partial polymer thereof. However, after the material is pulled up, there is a method of carrying out ultraviolet polymerization, radiation polymerization, or radical polymerization using a radical initiator. Examples of hydrophilic monomers include hydroxy lower alkyl acrylates such as 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, 3-hydroxypropyl acrylate, and 3-hydroxymethacrylate. or methacrylate, acrylamide, methacrylamide, N-
General formulas such as methylacrylamide, N-methylmethacrylamide, N-ethylacrylamide, N-ethylmethacrylamide, N-isopropylacrylamide, N-butylacrylamide, etc. (R 1 is hydrogen or an alkyl group having 1 to 4 carbon atoms, R 2 is
R 3 is hydrogen or an alkyl group. ), compounds such as acrylic acid, methacrylic acid, maleic acid or acid salts thereof, and N-vinyl compounds such as N-vinylpyrrolidone. Further, in order to increase the toughness of the coating layer, it is also possible to use a divinyl compound such as ethylene glycol diacrylate or ethylene glycol dimethacrylate as a crosslinking agent. In addition, as the hydrophilic resin, a polymer or copolymer containing at least one of the above monomers as a main component, a compound consisting of polycarboxylic acid and polyethylene oxide or polyvinyl alcohol, polyvinyl alcohol, ethylene-vinyl acetate copolymer, etc. Examples include saponified polymers. To produce a sustained-release antibacterial urinary catheter according to the method of the present invention, the urinary catheter is first imbibed with a solution containing a biguanide compound. For this purpose, for example, the simplest method is to immerse the urinary catheter in a solution containing a biguanide compound. In this case, the temperature of the solution containing the biguanide compound may be any temperature as long as it does not have a significant adverse effect on the antibacterial activity of the biguanide compound or the material of the urinary catheter;
10 to 150°C, particularly room temperature to 80°C is preferred. The preferred immersion time varies depending on the immersion temperature, but is usually about 5 minutes to 1 week, particularly about 10 minutes to 4 days. In the present invention, it is necessary to subsequently convert the biguanide compound absorbed into the urinary catheter into a poorly water-soluble compound. Poor water solubility here means that the solubility of the compound in 100 g of distilled water at 20°C is 0.001 to 3.0 g, preferably 0.005 g to 3.0 g.
Refers to items in the 2.0g range. Solubility in water
If the amount is less than 0.001 g, the local release amount will be low and the efficacy as a bactericidal agent will be reduced. On the other hand, if the amount exceeds 3.0 g, the antibacterial substance will diffuse rapidly into the urine, making it impossible to sustainably release the antibacterial agent over a long period of time. As poorly water-soluble biguanide compounds,
Biguanide compounds themselves and various acids such as their hydrochlorides, hydrobromides, nitrates, phosphates, sulfates, borates, carbonates, bicarbonates, benzoates, formates, tartrates, acetates, etc. I can give you salt. In order to convert the biguanide compound absorbed into the urinary catheter into a poorly water-soluble compound, for example, the urinary catheter that has absorbed the biguanide compound can be treated with hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, boric acid, carbonic acid,
Solutions of bicarbonate, benzoic acid, formic acid, tartaric acid, acetic acid, etc., solutions containing anions of the above acids, solutions containing polyvalent metal ions such as calcium ions and magnesium ions, or mixed solutions consisting of two or more of these. This can be done by immersion. In addition, by allowing the urinary catheter to absorb a salt containing the anion of the acid mentioned above in advance, and then immersing this catheter in a solution containing the biguanide compound, the biguanide compound absorbed by the urinary catheter can be converted into a poorly water-soluble compound. You can also change it to The PH and temperature of the solution during immersion may be any conditions as long as they do not have a significant adverse effect on the antibacterial properties of the biguanide compound or the material of the urinary catheter; ~80°C is preferred. The preferred immersion time varies depending on the immersion temperature, but is usually about 1 hour to 1 week, particularly about 2 hours to 48 hours. In the present invention, after these treatments, the urinary catheter may be dried at a temperature of 10 to 80°C, preferably 30 to 70°C, if necessary. Biguanide compounds form salts with various acids, but the solubility of the formed salts in water varies greatly depending on the type of acid used, and when a poorly water-soluble salt is formed, the antibacterial activity of the solution may decrease. There is sex. However, the concentration of chlorhexidine gluconate commonly used for bladder irrigation is 0.02
(W/V)%, and according to Akio Hatada et al., Monthly Yakuji, 15 , 2193 (1973), Pseudomonas is the causative agent of urinary tract infections.
aeruginosa, Proteus vulgaris, Escherichia
The minimum inhibitory concentration (MIC) of chlorhexidine against coli and Staphylococcus aureus is
10, 12.5, 1.25, and 1.0 μg/ml, so even if the solubility of the poorly water-soluble biguanide compound is about 0.001 g, it has sufficient antibacterial activity. As described above, the solubility of a poorly water-soluble biguanide compound differs depending on the type of acid salt, so according to the present invention, various types of acids, anions, or polyvalent metal ions are selected when converting a biguanide compound into a poorly water-soluble compound. By changing the solubility of the biguanide compound, it is possible to arbitrarily adjust the rate of sustained release of the antibacterial substance from the urinary catheter into the urine. As a result of performing the series of operations described above, if the amount of the poorly water-soluble biguanide compound held in the urinary catheter is small, the series of operations may be repeated until the desired amount is reached. As described above, according to the manufacturing method of the present invention, an antibacterial substance sustained release urinary catheter having a desired sustained release rate and sustained release period can be produced using a simpler method than conventional methods. The present invention will be explained in more detail below by giving examples. Note that "parts" in the examples mean "parts by weight." Example 1 A natural rubber Foley balloon catheter (Kousan Shoji) was immersed in a solution of 50 parts of chlorhexidyl gluconate dissolved in 50 parts of distilled water at room temperature for 72 hours, and then dried at 50°C. The dried catheter was immersed in an aqueous solution consisting of 10 parts of sodium chloride and 90 parts of distilled water at room temperature for 10 hours, and then dried at 50°C. Example 2 10 parts of sodium chloride was added to sodium sulfate heptahydrate
The same operation as in Example 1 was performed except that the amount was changed to 10 parts. Example 3 10 parts of sodium chloride was added to sodium carbonate monohydrate
The same operation as in Example 1 was performed except that the amount was changed to 10 parts. Example 4 The same procedure as in Example 1 was performed except that 10 parts of sodium chloride was replaced with 10 parts of sodium nitrate. Example 5 The procedure of Example 1 was repeated twice. Comparative Example 1 A natural rubber Foley balloon catheter (Kousan Shoji) was immersed in a solution consisting of 50 parts of chlorhexidyl gluconate and 50 parts of distilled water at room temperature for 72 hours, and then dried at 50°C. The catheters obtained in Examples 1 to 5 and Comparative Example 1 above were immersed in test urine at 37°C,
The antibacterial activity of each urine was tested using the cylindrical plate method (paper disk method) using Bacillus subtilis ATCC6633 as the test bacterium. The same antibacterial activity test was repeated by replacing the test urine with fresh test urine every day. The results are shown in Table 11
Claims (1)
ルに吸収させ、しかるのち導尿カテーテルに吸収
されたビグアニド化合物を水難溶性化合物に変え
ることを特徴とする抗菌物質徐放性導尿カテーテ
ルの製造方法。 2 ビグアニド化合物が1,6−ジ−(4−クロ
ロフエニルビグアニド)ヘキサンである特許請求
の範囲第1項記載の方法。[Claims] 1. An antibacterial substance sustained release urinary catheter characterized in that a solution containing a biguanide compound is absorbed into a urinary catheter, and the biguanide compound absorbed into the urinary catheter is then converted into a poorly water-soluble compound. manufacturing method. 2. The method according to claim 1, wherein the biguanide compound is 1,6-di-(4-chlorophenylbiguanide)hexane.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58145429A JPS6036064A (en) | 1983-08-08 | 1983-08-08 | Production of anti-bacterial substance solow releasing urea guiding catheter |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58145429A JPS6036064A (en) | 1983-08-08 | 1983-08-08 | Production of anti-bacterial substance solow releasing urea guiding catheter |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6036064A JPS6036064A (en) | 1985-02-25 |
JPH0310341B2 true JPH0310341B2 (en) | 1991-02-13 |
Family
ID=15385036
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP58145429A Granted JPS6036064A (en) | 1983-08-08 | 1983-08-08 | Production of anti-bacterial substance solow releasing urea guiding catheter |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6036064A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0781566A2 (en) | 1995-12-26 | 1997-07-02 | Toyo Boseki Kabushiki Kaisha | Organic solvent-soluble mucopolysaccharide, antibacterial antithrombogenic composition and medical material |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6395027A (en) * | 1986-10-08 | 1988-04-26 | オリンパス光学工業株式会社 | Medical tube |
US4925668A (en) * | 1989-01-18 | 1990-05-15 | Becton, Dickinson And Company | Anti-infective and lubricious medical articles and method for their preparation |
US5165952A (en) * | 1989-01-18 | 1992-11-24 | Becton, Dickinson And Company | Anti-infective and antithrombogenic medical articles and method for their preparation |
US6261271B1 (en) | 1989-01-18 | 2001-07-17 | Becton Dickinson And Company | Anti-infective and antithrombogenic medical articles and method for their preparation |
US5089205A (en) * | 1989-09-25 | 1992-02-18 | Becton, Dickinson And Company | Process for producing medical devices having antimicrobial properties |
US6558686B1 (en) * | 1995-11-08 | 2003-05-06 | Baylor College Of Medicine | Method of coating medical devices with a combination of antiseptics and antiseptic coating therefor |
AU2006265707B2 (en) * | 2005-07-01 | 2012-06-14 | Kane Biotech Inc. | Antimicrobial compositions for inhibiting growth and proliferation of a microbial biofilm on medical devices |
-
1983
- 1983-08-08 JP JP58145429A patent/JPS6036064A/en active Granted
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0781566A2 (en) | 1995-12-26 | 1997-07-02 | Toyo Boseki Kabushiki Kaisha | Organic solvent-soluble mucopolysaccharide, antibacterial antithrombogenic composition and medical material |
Also Published As
Publication number | Publication date |
---|---|
JPS6036064A (en) | 1985-02-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4675347A (en) | Antimicrobial latex composition | |
US6589591B1 (en) | Method for treating medical devices using glycerol and an antimicrobial agent | |
EP2754413B1 (en) | Medical devices containing nitroprusside and antimicrobial agents | |
EP0379271A2 (en) | Anti-infective and lubricious medical articles and method for their preparation | |
DE10242476B4 (en) | Antibiotic / antibiotics-polymer combination | |
JPH0261261B2 (en) | ||
EP0761243A1 (en) | Biostatic coatings and processes | |
JPH0310341B2 (en) | ||
KR20110071089A (en) | Elastomeric article having a broad spectrum antimicrobial agent and method of making | |
JPH0328224B2 (en) | ||
US20090076480A1 (en) | Active Ingredient-Containing Silicone Elastomers | |
Romanò et al. | Efficacy of a central venous catheter (Hydrocath®) loaded with teicoplanin in preventing subcutaneous staphylococcal infection in the mouse | |
KR102548671B1 (en) | Antimicrobial compositions comprising antimicrobial hydrogels effective against mature biofilms | |
JPH0364143B2 (en) | ||
US20070231391A1 (en) | Anti-microbial and hydrophilic article and methods for manufacturing the same | |
JPS62161377A (en) | Medical tool gradually releasing antibacterial agent | |
JPH0474026B2 (en) | ||
EP0520160A1 (en) | Process for antimicrobial treatment of polyurethane | |
JPH1024100A (en) | Manufacture of medical article | |
Zhang et al. | Antimicrobial modifications on critical care implants | |
NO972896L (en) | Medical article | |
US20230166001A1 (en) | Ionic Polymers for Medical Device Applications | |
US20230166007A1 (en) | Ionic Polymers For Medical Device Applications | |
Gilmore et al. | Antimicrobial devices | |
JPH0327213B2 (en) |