JPH0142275B2 - - Google Patents
Info
- Publication number
- JPH0142275B2 JPH0142275B2 JP58033682A JP3368283A JPH0142275B2 JP H0142275 B2 JPH0142275 B2 JP H0142275B2 JP 58033682 A JP58033682 A JP 58033682A JP 3368283 A JP3368283 A JP 3368283A JP H0142275 B2 JPH0142275 B2 JP H0142275B2
- Authority
- JP
- Japan
- Prior art keywords
- erythromycin
- acid
- dihydro
- isopropylidene
- reaction
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- -1 ethylsuccinyl Chemical group 0.000 claims description 4
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 229940041033 macrolides Drugs 0.000 claims 1
- 229960003276 erythromycin Drugs 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000000243 solution Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 239000012046 mixed solvent Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 10
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 10
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 150000008065 acid anhydrides Chemical class 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 244000005700 microbiome Species 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- YOWQWFMSQCOSBA-UHFFFAOYSA-N 2-methoxypropene Chemical compound COC(C)=C YOWQWFMSQCOSBA-UHFFFAOYSA-N 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000192125 Firmicutes Species 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- XFKCVVFQGHCLIP-UHFFFAOYSA-N 2-ethylbutanedioyl dichloride Chemical compound CCC(C(Cl)=O)CC(Cl)=O XFKCVVFQGHCLIP-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 150000002084 enol ethers Chemical class 0.000 description 2
- IDRYSCOQVVUBIJ-PPGFLMPOSA-N erythromycin B Chemical class O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@H]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)C)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 IDRYSCOQVVUBIJ-PPGFLMPOSA-N 0.000 description 2
- 229950001028 erythromycin propionate Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- QHMVQKOXILNZQR-ONEGZZNKSA-N (e)-1-methoxyprop-1-ene Chemical compound CO\C=C\C QHMVQKOXILNZQR-ONEGZZNKSA-N 0.000 description 1
- QHMVQKOXILNZQR-UHFFFAOYSA-N 1-methoxyprop-1-ene Chemical compound COC=CC QHMVQKOXILNZQR-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
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 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
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229930006677 Erythromycin A Natural products 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 241000588645 Neisseria sicca Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000606856 Pasteurella multocida Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-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
- 235000011054 acetic acid Nutrition 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 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
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000011421 subcutaneous treatment Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Description
æ¬çºæã¯æ°èŠãªååæãã¯ãã©ã€ãç³»æçç©
質ãç¹ã«ïŒâãžãããâ11ïŒ12ââã€ãœããã
ãªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ããã³ïŒâãžããã
â11ïŒ12ââã€ãœããããªãã³â4â³âãšãâãš
ãªã¹ããã€ã·ã³ïŒ¡èªå°äœã«é¢ãããã®ã§ããã ãšãªã¹ããã€ã·ã³ã¯ç±³åœç¹èš±ç¬¬2653899å·æ现
æžã«ç€ºãããããã«ãé©åœãªå¹å°ã§ã¹ãã¬ããã
ã€ã»ã¹ ãšãªã¹ã¬ãŠã¹ïŒStreptomyces
erythreusïŒã®èæ ªãå¹é€ããéã«ç£çãããæ
çç©è³ªã§ããããšãªã¹ããã€ã·ã³ã¯ïŒ¡ãšïŒ¢ã®äºã€
ã®åœ¢ã§ç£çããã次ã®æ§é åŒã§è¡šããããã ãšãªã¹ããã€ã·ã³ã®å€æ°ã®èªå°äœã¯ãã®çç©åŠ
çãŸãã¯è¬å¹åŠçç¹æ§ãæ¹è³ªããããšã«åªåãæ
ã€ãŠè£œé ãããŠããã ç±³åœç¹èš±ç¬¬3417077å·æ现æžã«ã¯éåžžã«æŽ»æ§ãª
æèå€ãšããŠã®ãšãªã¹ããã€ã·ã³ãšãšãã¬ã³ã«ãŒ
ãããŒããšã®åå¿çæç©ãèšèŒãããŠãããç±³åœ
ç¹èš±ç¬¬3884903å·æ现æžã«ã¯æçç©è³ªãšããŠæçš
ãª4â³âããªãã·â4â³âãªããœâãšãªã¹ããã€ã·ã³
ããã³ïŒ¢èªå°äœãé瀺ãããŠããããããŠç±³åœ
ç¹èš±ç¬¬4150220å·æ现æžã«ã¯4â³âãªããœâãšãªã¹
ããã€ã·ã³ã®æ°èŠåæãšæèå€ã«å°ãããã®äžé
äœãšããŠã®ãã®äœ¿çšãèšèŒãããŠããã ïŒâãžããããšãªã¹ããã€ã·ã³ïŒ¡ã¯K.Gerzon
çã«ããJ.Am.Chem.Soc.ã78ã6396ïŒ1956ïŒã
ãã³M.V.Sigalçã«ããJ.Am.Chem.Soc.ã78ã
388ïŒ1956ïŒã«å ±åãããŠããã æ¬çºæã®ååæãã¯ãã©ã€ãç³»æèå€ã¯æ¬¡åŒã§
è¡šããããååç©ããã³ãã®å»è¬ãšããŠé©åœãªé ž
ä»å å¡©ã§ããã
質ãç¹ã«ïŒâãžãããâ11ïŒ12ââã€ãœããã
ãªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ããã³ïŒâãžããã
â11ïŒ12ââã€ãœããããªãã³â4â³âãšãâãš
ãªã¹ããã€ã·ã³ïŒ¡èªå°äœã«é¢ãããã®ã§ããã ãšãªã¹ããã€ã·ã³ã¯ç±³åœç¹èš±ç¬¬2653899å·æ现
æžã«ç€ºãããããã«ãé©åœãªå¹å°ã§ã¹ãã¬ããã
ã€ã»ã¹ ãšãªã¹ã¬ãŠã¹ïŒStreptomyces
erythreusïŒã®èæ ªãå¹é€ããéã«ç£çãããæ
çç©è³ªã§ããããšãªã¹ããã€ã·ã³ã¯ïŒ¡ãšïŒ¢ã®äºã€
ã®åœ¢ã§ç£çããã次ã®æ§é åŒã§è¡šããããã ãšãªã¹ããã€ã·ã³ã®å€æ°ã®èªå°äœã¯ãã®çç©åŠ
çãŸãã¯è¬å¹åŠçç¹æ§ãæ¹è³ªããããšã«åªåãæ
ã€ãŠè£œé ãããŠããã ç±³åœç¹èš±ç¬¬3417077å·æ现æžã«ã¯éåžžã«æŽ»æ§ãª
æèå€ãšããŠã®ãšãªã¹ããã€ã·ã³ãšãšãã¬ã³ã«ãŒ
ãããŒããšã®åå¿çæç©ãèšèŒãããŠãããç±³åœ
ç¹èš±ç¬¬3884903å·æ现æžã«ã¯æçç©è³ªãšããŠæçš
ãª4â³âããªãã·â4â³âãªããœâãšãªã¹ããã€ã·ã³
ããã³ïŒ¢èªå°äœãé瀺ãããŠããããããŠç±³åœ
ç¹èš±ç¬¬4150220å·æ现æžã«ã¯4â³âãªããœâãšãªã¹
ããã€ã·ã³ã®æ°èŠåæãšæèå€ã«å°ãããã®äžé
äœãšããŠã®ãã®äœ¿çšãèšèŒãããŠããã ïŒâãžããããšãªã¹ããã€ã·ã³ïŒ¡ã¯K.Gerzon
çã«ããJ.Am.Chem.Soc.ã78ã6396ïŒ1956ïŒã
ãã³M.V.Sigalçã«ããJ.Am.Chem.Soc.ã78ã
388ïŒ1956ïŒã«å ±åãããŠããã æ¬çºæã®ååæãã¯ãã©ã€ãç³»æèå€ã¯æ¬¡åŒã§
è¡šããããååç©ããã³ãã®å»è¬ãšããŠé©åœãªé ž
ä»å å¡©ã§ããã
ãåŒã
ïŒåŒäžãã¯æ°ŽçŽ ãççŽ æ°ïŒãïŒã®ã¢ã«ã«ãã€ã«
ãŸãã¯ãšãã«ã¹ã¯ã·ãã«ã§ãããïŒå¥œãŸããåå
ç©ã®çŸ€ã¯ïŒ²ãæ°ŽçŽ ã§ãããã®ã§ããããã®çŸ€ã®å
ã«ç¹ã«å¥œãŸãããã®ã¯C4â³âããããã·ã«åºãã¢
ã¯ã·ã¢ã«çµåããŠããååç©ãšC4â³âããããã·
ã«åºããšã«ããªã¢ã«çµåããŠããååç©ã§ããã æ¬çºæååç©ãšè¬åŠçã«èš±å®¹ã§ããæ äœãšãã
ãªãå»è¬çµæç©ããã³ã°ã©ã éœæ§èãåå ã®ç æ°
ããã€åç©ã«æ¬çºæååç©ã®æèçã«æå¹ãªéã
æäžããããšãããªãåèšåç©ã®æ²»çæ¹æ³ã¯ãŸã
æ¬çºæã®ç¯å²å ã®ãã®ã§ããã C4â³âäœçœ®ã«èªç¶ã®ã³ã³ããŒã¡ãŒã·ãšã³ïŒç«äœ
é 座ïŒãæããæ¬çºæã®æèæ§ååç©ã¯ïŒâãžã
ãããšãªã¹ããã€ã·ã³ïŒ¡ããåºçºããŠæ¬¡ã®å³åŒã«
ããåæãããã å®éã«ã¯åå¿äžæŽ»æ§æº¶åªäžã®ïŒããšïŒâã¡ããã·
ãããã³ãšã®æ··åç©ãããªãžã³å¡©é žå¡©ãšå®€æž©ã«ã
ããŠåŠçãããã®çµæãšïŒãã®çŽïŒïŒïŒæ··åç©ã
çæãããïŒãã®ãžã®å€æã¯11ïŒ12ââã±ã¿ãŒ
ã«æ§é ãå解ããããšãªããã€æåã«çæãã
ãïŒãããåé¢ããããšãªãé žã§å æ°Žå解ããããš
ã«ããéæãããã ãã®æåã®åå¿ã¯ïŒãã®ïŒã¢ã«ããã10åã¢ã«ã®
ïŒâã¡ããã·ãããã³ã䜿çšããŠå®æœããããã
ãå°ãªãéã®ãšããŒã«ãšãŒãã«ã䜿çšããããšã
åºæ¥ããã®åéã¯ããå°ãªããã®ãšãªãããšã
ãŒã«ãšãŒãã«ã10åéããå€ããªããšçæããïŒã
ã®éãå¢å ããã䜿çšããïŒãã®ïŒã¢ã«ã«å¯ŸããŠã
ãªãžã³å¡©é žå¡©ã¯ããããïŒã¢ã«ã«ïŒã¢ã«éå°çšåºŠ
ãå ããéãçšããããã ããªãžã³å¡©é žå¡©ã¯æ°·æµŽæž©åºŠã§åå¿äžæŽ»æ§æº¶åªäž
ã®ïŒããšïŒâã¡ããã·ãããã³ã«å ãããããã®å
å¿æ··åç©ã¯å®€æž©ãŸã§æããããããšã奜ãŸããã
ãã®åå¿ã¯å®€æž©ã«ãããŠïŒã17æéã§çµäºããæ
å©ã«ã¯å€éãå®æœãããã åè¿°ã®å·¥çšãè¡ãªãããã®æº¶åªã«é¢ããŠã¯ãå
å¿äžæŽ»æ§æº¶åªã奜éœåã§ãããåå¿äžæŽ»æ§æº¶åªãš
ããã®ã¯é©åœãªè©Šè¬é¡ã溶解ããããåºçºè©Šè¬ãŸ
ãã¯æçµçæç©ã®ããããšãèªããããããªãçš
床ã«ãåå¿ããªããã®ãæå³ãããé©åœãªæº¶åªãŸ
ãã¯ãã®æ··åç©ã«ã¯ã¯ãããã«ã ãå¡©åã¡ãã¬ã³
ã®ãããªããã²ã³å溶åªããã«ãšã³ã®ãããªè³éŠ
æ溶åªããã³ããã©ããããã©ã³ããžãšãã«ãšãŒ
ãã«ã®ãããªãšãŒãã«é¡ãå«ãŸããã奜ãŸãã溶
åªã¯ã¯ãããã«ã ã§ããã åå¿ã®å®äºæç¹ã§ãã®æ··åç©ã¯PH9.5ã«ãããŠ
æ°ŽãçšããŠåå¿ãåæ¢ãããçæç©ããã³ïŒãã
PH3.6ã§æ°Žâã¢ã»ãã³æ··å溶åªäžã«æžæ¿ããŠïŒãã
ã«å€æããããã®å€æå·¥çšã¯æ瀺ãããPHã«ã
ããŠå®€æž©ã§çŽïŒæéæ¹æããªããè¡ãããããã
ãããã®PHãå¡©åºæ§ã«ããŠçæç©ãå¡©åã¡ãã¬
ã³ã®ãããªæ°Žäžåæ§æº¶åªã§æœåºãããçæç©ã®ç²Ÿ
補ã¯æ £çšæ段ã§å®æœãããã åŒã®ååç©ïŒããã§ïŒ²ã¯æ°ŽçŽ 以å€ã®å ã«å®çŸ©
ããéãã®ãã®ã§ããïŒã®è£œé ã¯ãé©åœãªé žç¡
æ°Žç©ãŸãã¯é žå¡©åç©ã§åŠçããããšã«ããéæã
ããã ãé žç¡æ°Žç©ã§åŠçããå Žåã«ã¯ãåå¿äžæŽ»æ§
溶åªäžã®ïŒã¢ã«ã¯å°ãªããšãïŒã¢ã«ã®é©åœãªé ž
ç¡æ°Žç©ãšåŠçãããããããŠãã®å Žåã«åå¿ã®å®
äºã確å®ãªãã®ãšããããã«50ïŒ çšåºŠéå°ã®é žç¡
æ°Žç©ã䜿çšããããšãæå©ã§ããã å®éã«ã¯é žç¡æ°Žç©ã¯ïŒâã§ã«å ããããçã
ãåå¿æ··åç©ã¯å®€æž©ã«ãŸã§æããããã宀枩ã«ã
ããŠãã®åå¿ã¯çŽïŒã12æéã§å®äºãã ã¢ã·ã«ååå¿ã®ããã®åå¿äžæŽ»æ§æº¶åªã¯åã«å®
矩ãããã®ãšåãæ§è³ªãæããŠããã¹ãã§ããã
奜ãŸãã溶åªã¯å¡©åã¡ãã¬ã³ãŸãã¯ã¢ã»ãã³ã§ã
ããåå¿ã®å®äºæç¹ã§æ··åç©ãPH9.5ã«ãããŠæ°Ž
ã§åŠçããçæç©ã¯æ°Žäžæ··åæ§æº¶åªã§æœåºããã
çæç©ã®åé¢ããã³ç²Ÿè£œã¯æ £çšæ段ã§è¡ãããã ã¢ã·ã«åå€ãšããŠé žå¡©åç©ã䜿çšããå Žåã«ã
ãã®åå¿ã¯é žç¡æ°Žç©ã䜿çšããå Žåãšæ¬è³ªçã«å
ãæ¹æ³ã§è¡ããããããæ ãé žå¡©åç©ã¯ïŒâã§å
å¿äžæŽ»æ§æº¶åªäžã®ã«å ãããããã®åå¿æ··åç©
ãåå¿æéäžãã®æž©åºŠã«ç¶æããããããã®åå¿
æ¡ä»¶äžã«ãããŠã¢ã·ã«åã¯çŽïŒãïŒæéã§å®äºã
ãã é žç¡æ°Žç©ã§ã®ã¢ã·ã«åã®å Žåã®ããã«ãé žå¡©å
ç©ã®éå°éã䜿çšããŠåå¿ãå®çµãããã®ãæå©
ã§ããã ã¢ã·ã«åå€ãšããŠé žå¡©åç©ã䜿çšããå Žåã«ã
çæããå¡©åæ°ŽçŽ ã®é žæå»å€ãšããŠçé žæ°ŽçŽ ãã
ãªãŠã ãå ããããããã®ãããªå Žåã«ããã¯ã
ã©ã€ãã«çããã¢ã«éã«ããéå°éãå ããéã
çšããããã åŸãããçæç©ã¯ã®åæã§é žç¡æ°Žç©ã䜿çšã
ãå Žåã«ãããŠåã«è¿°ã¹ãæ¹æ³ãšåãæ¹æ³ã§åé¢
ãã粟補ãããã C4â³âäœçœ®ã«é倩ç¶ã®ã³ã³ããŒã¡ãŒã·ãšã³ãæ
ããæ¬çºæã®æèæ§ååç©ã¯4â³âããªãã·â4â³â
ãªããœâãšãªã¹ããã€ã·ã³ïŒ¡ããåºçºããŠæ¬¡ã®å³
åŒããåæãããã å®éã«ã¯ïŒããçŽ95.2æ°å§ïŒçŽ1400psiïŒã«ãã
ãŠã©ããŒããã±ã«è§Šåªã§å€éãæ°ŽçŽ æ·»å ããŠäžé
äœïŒãã®ïŒâãžãããâ4â³âãšãâãšãªã¹ããã€ã·
ã³ïŒ¡ãçæããã äžéäœïŒãã¯ïŒãã«ã€ããŠåã«è¿°ã¹ããã®ãšåãå®
éšæ¡ä»¶äžã«ïŒâã¡ããã·ãããã³ãšåå¿ããŠ11ïŒ
12ââã±ã¿ãŒã«ãšïŒãã®æ··åç©ãçãããåå
ç©ïŒãã¯ïŒããPHçŽ3.5ã§é žã䜿çšããŠã«å€æãã
ãã®ãšå šãåãæ¹æ³ã§ã«å€æãããã ããã«åŒã®2â²âãšã¹ãã«ååç©ã¯åŒã®åå
ç©ã«å¯ŸããŠäœ¿çšããæ¹æ³ãšåãæ¹æ³ã§è£œé ãã
ãã æ¬çºæååç©ã«å°ãå·¥çšã§äœ¿çšããè©Šè¬é¡ã¯åœ
該æè¡åéã«ãããŠæ¢ç¥ã§ããã4â³âããªãã·â
4â³âãªããœâãšãªã¹ããã€ã·ã³ïŒ¡ã®è£œæ³ã¯ç±³åœç¹
蚱第4150220å·æ现æžã«å ±åãããŠãããïŒâãž
ããããšãªã¹ããã€ã·ã³ïŒ¡ã®è£œæ³ã¯J.Am.Chem.
Soc.ã78ã388ïŒ1956ïŒã«å ±åãããŠããã æ¬çºæã®æèæ§ååç©ã®ãã¡ã§å¥œãŸãããã®ã¯
ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³â
ãšãªã¹ããã€ã·ã³ïŒ¡ãšïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³â4â³âãšãâãšãªã¹ããã€ã·
ã³ïŒ¡ã§ããããããã¯ïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ã®
C4â³âãšã¯ã¢ããªã¢ã«ãšC4â³ã®ç°æ§äœã§ããã ãããã®æ¬çºæååç©ã®å¡©åœ¢ããã®ååŠçæ³æŽ»
æ§ã®ç¹ã§å©çšããã«ãããŠãå»è¬ãšããŠé©åœãªå¡©
ã䜿çšããããšã¯ãã¡ãã奜ãŸããããšã§ããã
ããã€ãã®ç¹å®ã®å¡©ã¯æ°Žäžæº¶è§£æ§ãé«æ¯æ§ãŸãã¯
å¡©æ¶æ§ã®æ¬ ä¹ã®ããã«äžå®ã®è¬åŠçé©çšã«ãããŠ
ãã®ãŸãŸã§äœ¿çšããã«ã¯äžé©åœã§ãããŸãæãŸã
ããã®ã§ã¯ãªããããã®æ°Žäžæº¶è§£æ§ãŸãã¯æ¯æ§å¡©
ã¯ãã®å¡©ãå解ããããšã«ãã察å¿ããå»è¬ãšã
ãŠé©åœãªå¡©åºã«å€æãããããŸãå¥ã®æ¹æ³ãšããŠ
ã¯ãããã¯ææã®å»è¬ãšããŠé©åœãªé žä»å å¡©ã«å€
æã§ããã å»è¬ãšããŠé©åœãªé°ã€ãªã³ãäžããé žã®äŸãšã
ãŠã¯ãå¡©é žãèåæ°ŽçŽ é žããšãŠåæ°ŽçŽ é žãç¡é žã
ç¡«é žãäºç¡«é žãçé žãé ¢é žãä¹³é žãã¯ãšã³é žãé
ç³é žãã³ãã¯é žããã¬ã€ã³é žãã°ã«ã³ã³é žããã³
ã¢ã¹ãã©ã®ã³é žãããã ããã«è¿°ã¹ãæ°èŠãªãšãªã¹ããã€ã·ã³é¡ã¯é»è²
ãããŠçèïŒStaphylococcus aureusïŒãã¬ã³
ãµçèïŒStreptococcus pyogenesïŒã®ãããª
çš®ã ã®ã°ã©ã éœæ§èããã³ç圢ãæ¥å圢ãããè
ïŒçç¶èïŒã®ãããªããçš®ã®ã°ã©ã é°æ§èã«å¯Ÿã
ãŠçäœå€ã§æŽ»æ§ã瀺ãããããã®æŽ»æ§ã¯éåžžã®ïŒ
åé次åžéæ³ãçšããŠè³å¿è浞åºæ¶²å¹å°äžã®çš®ã
ã®åŸ®çç©ã«å¯Ÿããçäœå€è©Šéšã«ãã容æã«ç«èšŒã
ããããããã®çäœå€ã§ã®æŽ»æ§ã«ãããããã¯è»
èãã¯ãªãŒã çã®åœ¢äœã§ã®å€çšå€ã«ïŒç 宀ã®çšå ·
çã®æ®ºèæ¶æ¯ç®çã«ïŒãããŠæ°ŽåŠçãã¹ã©ã€ã æ
å¶ãŸãã¯å¡æãæšæã®é²è çã«ãããå·¥æ¥çšæè
ç©è³ªãšããŠæçšãªãã®ã§ããã çäœå€ã§ã®äœ¿çšãããšãã°å€çšå€ã®ããã«ã¯ã
æå®ã®çæç©ãæ€ç©æ²¹ãé±æ²¹ãŸãã¯ç®èè»åçšã¯
ãªãŒã ã®ãããªè¬åŠçã«èš±å®¹ã§ããæ äœãšé åã
ãããšããã°ãã°éœåã®ããããšã§ãããåæ§
ã«ãããã¯æ°Žãã¢ã«ã³ãŒã«ãã°ãªã³ãŒã«ãŸãã¯ã
ããã®æ··åç©ã®ãããªæ¶²ç¶æ äœã溶åªããããã¯
ä»ã®è¬åŠçã«èš±å®¹ã§ããäžæŽ»æ§åªäœããªãã¡æŽ»æ§
æåã«å¯ŸããŠæ害ãªåœ±é¿ãåãŒããªãåªäœã«æº¶è§£
ããŠãããããŸãåæ£ããŠãããããã®ãããªç®
çã®ããã«ãå šçµæç©ã«åºã¥ããŠçŽ0.01ãçŽ10é
éïŒ ã®æŽ»æ§æåæ¿åºŠãçšããããã®ããšã¯äžè¬ã«
èªããããšããã§ããã ããã«ãæ¬çºæååç©ã®å€ãã¯åç©ïŒãããå«
ãïŒãžã®çµå£ããã³ïŒãŸãã¯éçµå£æäžçµè·¯ã§ç
äœå ã®ã°ã©ã éœæ§èããã³ãã¹ããŠã¬ã© ã ã«ã
ã·ãïŒPasteurella multocidaïŒãã¢ãã€ã«ã¹
ã€ã³ãã«ãšã³ã¶ïŒHemophilus influenzaïŒãã
ã³ãã€ã»ãªã¢ ã·ãã«ïŒNeisseria siccaïŒã®ã
ããªããçš®ã®ã°ã©ã é°æ§èã«å¯ŸããŠæŽ»æ§ã§ããã
圱é¿ãåãããã埮çç©ã«é¢ããŠèšãã°ãããã
ã®çäœå 掻æ§ã¯ããã«éå®ããããããŠãããã®
掻æ§åºŠã¯å®è³ªçã«åäžãªäœéãæããããã«ããº
ãã«è©ŠéšåŸ®çç©ãåŠçãã次ãã§ããããè©Šéšå
åç©ã§çµå£çã«ãŸãã¯ç®äžçã«åŠçããããšãã
ãªãéåžžã®æ¹æ³ã§æ±ºå®ããããå®éã«ã¯ããã«ã
ãºããããšãã°10å¹ã«LD100ïŒ100ïŒ èŽæ»ã«èŠãã
埮çç©ã®æäœæ¿åºŠïŒã®çŽïŒã10åéãå«æããé©
åœãªåžéåé€æ¶²ãè ¹è å æ¥çš®ãããåæã«å¯Ÿç §è©Š
éšãå®æœãããã®è©Šéšã«ãããŠããã«ããºãã¯è©Š
éšåŸ®çç©ã®èåã®ãããããå€åãããšãã¯ãã
ãã®ãšããŠããäœæ¿åºŠã®åžé液ãæ¥çš®ããããè©Š
éšååç©ã¯æ¥çš®åŸ0.5æéã«æäžããããããŠïŒã
24ããã³48æéåŸã«ç¹°ãè¿ããããæåŸã®åŠçã®
åŸã«çãæ®ã€ãŠããããã«ããºããïŒæ¥éä¿ã¡ã
ãããŠçåããŠãããã®ã®æ°ãèšé²ããã ããã§ãæ¬çºæã®ååç©ïŒäžèšååç©ããã³
ïŒãšããããšæ§é è¿äŒŒã®å ¬ç¥ååç©ïŒäžèšåå
ç©ïŒã«ã€ããŠå皮埮çç©ã«å¯Ÿããæå°é»æ¢æ¿åºŠ
ïŒMICïŒããã³PD50å€ãäžè¡šã«ç€ºãã ååç©ïŒïŒâãžããããšãªã¹ããã€ã·ã³ïŒ¡ ååç©ïŒïŒâãžãããâ11ïŒ12ââã€ãœãã
ããªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ ååç©ïŒïŒâãžãããâ11ïŒ12ââã€ãœãã
ããªãã³â4â³âãšãâãšãªã¹ããã€ã·ã³ïŒ¡
ãŸãã¯ãšãã«ã¹ã¯ã·ãã«ã§ãããïŒå¥œãŸããåå
ç©ã®çŸ€ã¯ïŒ²ãæ°ŽçŽ ã§ãããã®ã§ããããã®çŸ€ã®å
ã«ç¹ã«å¥œãŸãããã®ã¯C4â³âããããã·ã«åºãã¢
ã¯ã·ã¢ã«çµåããŠããååç©ãšC4â³âããããã·
ã«åºããšã«ããªã¢ã«çµåããŠããååç©ã§ããã æ¬çºæååç©ãšè¬åŠçã«èš±å®¹ã§ããæ äœãšãã
ãªãå»è¬çµæç©ããã³ã°ã©ã éœæ§èãåå ã®ç æ°
ããã€åç©ã«æ¬çºæååç©ã®æèçã«æå¹ãªéã
æäžããããšãããªãåèšåç©ã®æ²»çæ¹æ³ã¯ãŸã
æ¬çºæã®ç¯å²å ã®ãã®ã§ããã C4â³âäœçœ®ã«èªç¶ã®ã³ã³ããŒã¡ãŒã·ãšã³ïŒç«äœ
é 座ïŒãæããæ¬çºæã®æèæ§ååç©ã¯ïŒâãžã
ãããšãªã¹ããã€ã·ã³ïŒ¡ããåºçºããŠæ¬¡ã®å³åŒã«
ããåæãããã å®éã«ã¯åå¿äžæŽ»æ§æº¶åªäžã®ïŒããšïŒâã¡ããã·
ãããã³ãšã®æ··åç©ãããªãžã³å¡©é žå¡©ãšå®€æž©ã«ã
ããŠåŠçãããã®çµæãšïŒãã®çŽïŒïŒïŒæ··åç©ã
çæãããïŒãã®ãžã®å€æã¯11ïŒ12ââã±ã¿ãŒ
ã«æ§é ãå解ããããšãªããã€æåã«çæãã
ãïŒãããåé¢ããããšãªãé žã§å æ°Žå解ããããš
ã«ããéæãããã ãã®æåã®åå¿ã¯ïŒãã®ïŒã¢ã«ããã10åã¢ã«ã®
ïŒâã¡ããã·ãããã³ã䜿çšããŠå®æœããããã
ãå°ãªãéã®ãšããŒã«ãšãŒãã«ã䜿çšããããšã
åºæ¥ããã®åéã¯ããå°ãªããã®ãšãªãããšã
ãŒã«ãšãŒãã«ã10åéããå€ããªããšçæããïŒã
ã®éãå¢å ããã䜿çšããïŒãã®ïŒã¢ã«ã«å¯ŸããŠã
ãªãžã³å¡©é žå¡©ã¯ããããïŒã¢ã«ã«ïŒã¢ã«éå°çšåºŠ
ãå ããéãçšããããã ããªãžã³å¡©é žå¡©ã¯æ°·æµŽæž©åºŠã§åå¿äžæŽ»æ§æº¶åªäž
ã®ïŒããšïŒâã¡ããã·ãããã³ã«å ãããããã®å
å¿æ··åç©ã¯å®€æž©ãŸã§æããããããšã奜ãŸããã
ãã®åå¿ã¯å®€æž©ã«ãããŠïŒã17æéã§çµäºããæ
å©ã«ã¯å€éãå®æœãããã åè¿°ã®å·¥çšãè¡ãªãããã®æº¶åªã«é¢ããŠã¯ãå
å¿äžæŽ»æ§æº¶åªã奜éœåã§ãããåå¿äžæŽ»æ§æº¶åªãš
ããã®ã¯é©åœãªè©Šè¬é¡ã溶解ããããåºçºè©Šè¬ãŸ
ãã¯æçµçæç©ã®ããããšãèªããããããªãçš
床ã«ãåå¿ããªããã®ãæå³ãããé©åœãªæº¶åªãŸ
ãã¯ãã®æ··åç©ã«ã¯ã¯ãããã«ã ãå¡©åã¡ãã¬ã³
ã®ãããªããã²ã³å溶åªããã«ãšã³ã®ãããªè³éŠ
æ溶åªããã³ããã©ããããã©ã³ããžãšãã«ãšãŒ
ãã«ã®ãããªãšãŒãã«é¡ãå«ãŸããã奜ãŸãã溶
åªã¯ã¯ãããã«ã ã§ããã åå¿ã®å®äºæç¹ã§ãã®æ··åç©ã¯PH9.5ã«ãããŠ
æ°ŽãçšããŠåå¿ãåæ¢ãããçæç©ããã³ïŒãã
PH3.6ã§æ°Žâã¢ã»ãã³æ··å溶åªäžã«æžæ¿ããŠïŒãã
ã«å€æããããã®å€æå·¥çšã¯æ瀺ãããPHã«ã
ããŠå®€æž©ã§çŽïŒæéæ¹æããªããè¡ãããããã
ãããã®PHãå¡©åºæ§ã«ããŠçæç©ãå¡©åã¡ãã¬
ã³ã®ãããªæ°Žäžåæ§æº¶åªã§æœåºãããçæç©ã®ç²Ÿ
補ã¯æ £çšæ段ã§å®æœãããã åŒã®ååç©ïŒããã§ïŒ²ã¯æ°ŽçŽ 以å€ã®å ã«å®çŸ©
ããéãã®ãã®ã§ããïŒã®è£œé ã¯ãé©åœãªé žç¡
æ°Žç©ãŸãã¯é žå¡©åç©ã§åŠçããããšã«ããéæã
ããã ãé žç¡æ°Žç©ã§åŠçããå Žåã«ã¯ãåå¿äžæŽ»æ§
溶åªäžã®ïŒã¢ã«ã¯å°ãªããšãïŒã¢ã«ã®é©åœãªé ž
ç¡æ°Žç©ãšåŠçãããããããŠãã®å Žåã«åå¿ã®å®
äºã確å®ãªãã®ãšããããã«50ïŒ çšåºŠéå°ã®é žç¡
æ°Žç©ã䜿çšããããšãæå©ã§ããã å®éã«ã¯é žç¡æ°Žç©ã¯ïŒâã§ã«å ããããçã
ãåå¿æ··åç©ã¯å®€æž©ã«ãŸã§æããããã宀枩ã«ã
ããŠãã®åå¿ã¯çŽïŒã12æéã§å®äºãã ã¢ã·ã«ååå¿ã®ããã®åå¿äžæŽ»æ§æº¶åªã¯åã«å®
矩ãããã®ãšåãæ§è³ªãæããŠããã¹ãã§ããã
奜ãŸãã溶åªã¯å¡©åã¡ãã¬ã³ãŸãã¯ã¢ã»ãã³ã§ã
ããåå¿ã®å®äºæç¹ã§æ··åç©ãPH9.5ã«ãããŠæ°Ž
ã§åŠçããçæç©ã¯æ°Žäžæ··åæ§æº¶åªã§æœåºããã
çæç©ã®åé¢ããã³ç²Ÿè£œã¯æ £çšæ段ã§è¡ãããã ã¢ã·ã«åå€ãšããŠé žå¡©åç©ã䜿çšããå Žåã«ã
ãã®åå¿ã¯é žç¡æ°Žç©ã䜿çšããå Žåãšæ¬è³ªçã«å
ãæ¹æ³ã§è¡ããããããæ ãé žå¡©åç©ã¯ïŒâã§å
å¿äžæŽ»æ§æº¶åªäžã®ã«å ãããããã®åå¿æ··åç©
ãåå¿æéäžãã®æž©åºŠã«ç¶æããããããã®åå¿
æ¡ä»¶äžã«ãããŠã¢ã·ã«åã¯çŽïŒãïŒæéã§å®äºã
ãã é žç¡æ°Žç©ã§ã®ã¢ã·ã«åã®å Žåã®ããã«ãé žå¡©å
ç©ã®éå°éã䜿çšããŠåå¿ãå®çµãããã®ãæå©
ã§ããã ã¢ã·ã«åå€ãšããŠé žå¡©åç©ã䜿çšããå Žåã«ã
çæããå¡©åæ°ŽçŽ ã®é žæå»å€ãšããŠçé žæ°ŽçŽ ãã
ãªãŠã ãå ããããããã®ãããªå Žåã«ããã¯ã
ã©ã€ãã«çããã¢ã«éã«ããéå°éãå ããéã
çšããããã åŸãããçæç©ã¯ã®åæã§é žç¡æ°Žç©ã䜿çšã
ãå Žåã«ãããŠåã«è¿°ã¹ãæ¹æ³ãšåãæ¹æ³ã§åé¢
ãã粟補ãããã C4â³âäœçœ®ã«é倩ç¶ã®ã³ã³ããŒã¡ãŒã·ãšã³ãæ
ããæ¬çºæã®æèæ§ååç©ã¯4â³âããªãã·â4â³â
ãªããœâãšãªã¹ããã€ã·ã³ïŒ¡ããåºçºããŠæ¬¡ã®å³
åŒããåæãããã å®éã«ã¯ïŒããçŽ95.2æ°å§ïŒçŽ1400psiïŒã«ãã
ãŠã©ããŒããã±ã«è§Šåªã§å€éãæ°ŽçŽ æ·»å ããŠäžé
äœïŒãã®ïŒâãžãããâ4â³âãšãâãšãªã¹ããã€ã·
ã³ïŒ¡ãçæããã äžéäœïŒãã¯ïŒãã«ã€ããŠåã«è¿°ã¹ããã®ãšåãå®
éšæ¡ä»¶äžã«ïŒâã¡ããã·ãããã³ãšåå¿ããŠ11ïŒ
12ââã±ã¿ãŒã«ãšïŒãã®æ··åç©ãçãããåå
ç©ïŒãã¯ïŒããPHçŽ3.5ã§é žã䜿çšããŠã«å€æãã
ãã®ãšå šãåãæ¹æ³ã§ã«å€æãããã ããã«åŒã®2â²âãšã¹ãã«ååç©ã¯åŒã®åå
ç©ã«å¯ŸããŠäœ¿çšããæ¹æ³ãšåãæ¹æ³ã§è£œé ãã
ãã æ¬çºæååç©ã«å°ãå·¥çšã§äœ¿çšããè©Šè¬é¡ã¯åœ
該æè¡åéã«ãããŠæ¢ç¥ã§ããã4â³âããªãã·â
4â³âãªããœâãšãªã¹ããã€ã·ã³ïŒ¡ã®è£œæ³ã¯ç±³åœç¹
蚱第4150220å·æ现æžã«å ±åãããŠãããïŒâãž
ããããšãªã¹ããã€ã·ã³ïŒ¡ã®è£œæ³ã¯J.Am.Chem.
Soc.ã78ã388ïŒ1956ïŒã«å ±åãããŠããã æ¬çºæã®æèæ§ååç©ã®ãã¡ã§å¥œãŸãããã®ã¯
ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³â
ãšãªã¹ããã€ã·ã³ïŒ¡ãšïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³â4â³âãšãâãšãªã¹ããã€ã·
ã³ïŒ¡ã§ããããããã¯ïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ã®
C4â³âãšã¯ã¢ããªã¢ã«ãšC4â³ã®ç°æ§äœã§ããã ãããã®æ¬çºæååç©ã®å¡©åœ¢ããã®ååŠçæ³æŽ»
æ§ã®ç¹ã§å©çšããã«ãããŠãå»è¬ãšããŠé©åœãªå¡©
ã䜿çšããããšã¯ãã¡ãã奜ãŸããããšã§ããã
ããã€ãã®ç¹å®ã®å¡©ã¯æ°Žäžæº¶è§£æ§ãé«æ¯æ§ãŸãã¯
å¡©æ¶æ§ã®æ¬ ä¹ã®ããã«äžå®ã®è¬åŠçé©çšã«ãããŠ
ãã®ãŸãŸã§äœ¿çšããã«ã¯äžé©åœã§ãããŸãæãŸã
ããã®ã§ã¯ãªããããã®æ°Žäžæº¶è§£æ§ãŸãã¯æ¯æ§å¡©
ã¯ãã®å¡©ãå解ããããšã«ãã察å¿ããå»è¬ãšã
ãŠé©åœãªå¡©åºã«å€æãããããŸãå¥ã®æ¹æ³ãšããŠ
ã¯ãããã¯ææã®å»è¬ãšããŠé©åœãªé žä»å å¡©ã«å€
æã§ããã å»è¬ãšããŠé©åœãªé°ã€ãªã³ãäžããé žã®äŸãšã
ãŠã¯ãå¡©é žãèåæ°ŽçŽ é žããšãŠåæ°ŽçŽ é žãç¡é žã
ç¡«é žãäºç¡«é žãçé žãé ¢é žãä¹³é žãã¯ãšã³é žãé
ç³é žãã³ãã¯é žããã¬ã€ã³é žãã°ã«ã³ã³é žããã³
ã¢ã¹ãã©ã®ã³é žãããã ããã«è¿°ã¹ãæ°èŠãªãšãªã¹ããã€ã·ã³é¡ã¯é»è²
ãããŠçèïŒStaphylococcus aureusïŒãã¬ã³
ãµçèïŒStreptococcus pyogenesïŒã®ãããª
çš®ã ã®ã°ã©ã éœæ§èããã³ç圢ãæ¥å圢ãããè
ïŒçç¶èïŒã®ãããªããçš®ã®ã°ã©ã é°æ§èã«å¯Ÿã
ãŠçäœå€ã§æŽ»æ§ã瀺ãããããã®æŽ»æ§ã¯éåžžã®ïŒ
åé次åžéæ³ãçšããŠè³å¿è浞åºæ¶²å¹å°äžã®çš®ã
ã®åŸ®çç©ã«å¯Ÿããçäœå€è©Šéšã«ãã容æã«ç«èšŒã
ããããããã®çäœå€ã§ã®æŽ»æ§ã«ãããããã¯è»
èãã¯ãªãŒã çã®åœ¢äœã§ã®å€çšå€ã«ïŒç 宀ã®çšå ·
çã®æ®ºèæ¶æ¯ç®çã«ïŒãããŠæ°ŽåŠçãã¹ã©ã€ã æ
å¶ãŸãã¯å¡æãæšæã®é²è çã«ãããå·¥æ¥çšæè
ç©è³ªãšããŠæçšãªãã®ã§ããã çäœå€ã§ã®äœ¿çšãããšãã°å€çšå€ã®ããã«ã¯ã
æå®ã®çæç©ãæ€ç©æ²¹ãé±æ²¹ãŸãã¯ç®èè»åçšã¯
ãªãŒã ã®ãããªè¬åŠçã«èš±å®¹ã§ããæ äœãšé åã
ãããšããã°ãã°éœåã®ããããšã§ãããåæ§
ã«ãããã¯æ°Žãã¢ã«ã³ãŒã«ãã°ãªã³ãŒã«ãŸãã¯ã
ããã®æ··åç©ã®ãããªæ¶²ç¶æ äœã溶åªããããã¯
ä»ã®è¬åŠçã«èš±å®¹ã§ããäžæŽ»æ§åªäœããªãã¡æŽ»æ§
æåã«å¯ŸããŠæ害ãªåœ±é¿ãåãŒããªãåªäœã«æº¶è§£
ããŠãããããŸãåæ£ããŠãããããã®ãããªç®
çã®ããã«ãå šçµæç©ã«åºã¥ããŠçŽ0.01ãçŽ10é
éïŒ ã®æŽ»æ§æåæ¿åºŠãçšããããã®ããšã¯äžè¬ã«
èªããããšããã§ããã ããã«ãæ¬çºæååç©ã®å€ãã¯åç©ïŒãããå«
ãïŒãžã®çµå£ããã³ïŒãŸãã¯éçµå£æäžçµè·¯ã§ç
äœå ã®ã°ã©ã éœæ§èããã³ãã¹ããŠã¬ã© ã ã«ã
ã·ãïŒPasteurella multocidaïŒãã¢ãã€ã«ã¹
ã€ã³ãã«ãšã³ã¶ïŒHemophilus influenzaïŒãã
ã³ãã€ã»ãªã¢ ã·ãã«ïŒNeisseria siccaïŒã®ã
ããªããçš®ã®ã°ã©ã é°æ§èã«å¯ŸããŠæŽ»æ§ã§ããã
圱é¿ãåãããã埮çç©ã«é¢ããŠèšãã°ãããã
ã®çäœå 掻æ§ã¯ããã«éå®ããããããŠãããã®
掻æ§åºŠã¯å®è³ªçã«åäžãªäœéãæããããã«ããº
ãã«è©ŠéšåŸ®çç©ãåŠçãã次ãã§ããããè©Šéšå
åç©ã§çµå£çã«ãŸãã¯ç®äžçã«åŠçããããšãã
ãªãéåžžã®æ¹æ³ã§æ±ºå®ããããå®éã«ã¯ããã«ã
ãºããããšãã°10å¹ã«LD100ïŒ100ïŒ èŽæ»ã«èŠãã
埮çç©ã®æäœæ¿åºŠïŒã®çŽïŒã10åéãå«æããé©
åœãªåžéåé€æ¶²ãè ¹è å æ¥çš®ãããåæã«å¯Ÿç §è©Š
éšãå®æœãããã®è©Šéšã«ãããŠããã«ããºãã¯è©Š
éšåŸ®çç©ã®èåã®ãããããå€åãããšãã¯ãã
ãã®ãšããŠããäœæ¿åºŠã®åžé液ãæ¥çš®ããããè©Š
éšååç©ã¯æ¥çš®åŸ0.5æéã«æäžããããããŠïŒã
24ããã³48æéåŸã«ç¹°ãè¿ããããæåŸã®åŠçã®
åŸã«çãæ®ã€ãŠããããã«ããºããïŒæ¥éä¿ã¡ã
ãããŠçåããŠãããã®ã®æ°ãèšé²ããã ããã§ãæ¬çºæã®ååç©ïŒäžèšååç©ããã³
ïŒãšããããšæ§é è¿äŒŒã®å ¬ç¥ååç©ïŒäžèšåå
ç©ïŒã«ã€ããŠå皮埮çç©ã«å¯Ÿããæå°é»æ¢æ¿åºŠ
ïŒMICïŒããã³PD50å€ãäžè¡šã«ç€ºãã ååç©ïŒïŒâãžããããšãªã¹ããã€ã·ã³ïŒ¡ ååç©ïŒïŒâãžãããâ11ïŒ12ââã€ãœãã
ããªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ ååç©ïŒïŒâãžãããâ11ïŒ12ââã€ãœãã
ããªãã³â4â³âãšãâãšãªã¹ããã€ã·ã³ïŒ¡
ãè¡šã
ãè¡šã
è¡šïŒããã³ïŒã®çµæãããå
¬ç¥è¿äŒŒååç©ã«
æ¯èŒããŠæ¬çºæååç©ããã³ãææã«ããã
ãå¹æãæããããšã¯æããã§ããã ãããã®æ°èŠååç©ãçäœå ã§äœ¿çšãããå Ž
åããããã¯çµå£çã«ãŸãã¯éçµå£çã«ããšãã°
ç®äžæ³šå°ãçèå 泚å°ã«ããäžæ¥ãããçŽ25mgïŒ
KgïŒäœéïŒãçŽ200mgïŒKgã®éã§æäžããããé©
åœãªæè¬ç¯å²ã¯äžæ¥ãããçŽ150mgïŒKgãçŽ200
mgïŒKgã§ããã泚å°å€ã«é©ããããã¯ã«ã¯æ°Žãç
çé£å¡©æ¶²ããããŠç³ç匵液ããã³ãªã³ã²ã«æ¶²ã®ã
ããªæ°Žæ§ã®ãã®ã§ãããããããã¯æ€ç©ããã®è
èªæ²¹ïŒç¶¿å®æ²¹ãããŒãããæ²¹ãã³ãŒã³æ²¹ãããŸ
æ²¹ïŒããžã¡ãã«ã¹ã«ããã·ãããã³è£œå€ã®æ²»çå¹
åã劚ãããŸã䜿çšããã容éãå²åã§éæ¯æ§ã§
ããä»ã®éæ°Žæ§ããã¯ã«é¡ïŒã°ãªã»ãªã³ãããã
ã¬ã³ã°ãªã³ãŒã«ããœã«ãããŒã«ïŒã®ãããªéæ°Žæ§
ã®ãã®ã§ãããããã«æäžåã«æ¶²å€ãçšæé補ã
ãã®ã«é©ããçµæç©ãæå©ã«äœãããããã®ãã
ãªçµæç©ã¯æ¶²ç¶åžéå€ïŒããšãã°ãããã¬ã³ã°ãª
ã³ãŒã«ããžãšãã«ã«ãŒãããŒããã°ãªã»ãªã³ããœ
ã«ãããŒã«çïŒãç·©è¡å€ããã¢ã«ãŠããããŒãŒã
å±æ麻é è¬ããã³ææã®å»è¬æ§è³ªãä»äžãããã
ã®ç¡æ©å¡©ãå«ãã§ããŠãããããããã®ååç©ã¯
ãŸãã«ãã»ã«å€ãé å€ãããŒã³ãžå€ããããŒã
å€ã也ç¥è£œå€ãæžæ¿å€ã液å€ããšãªãã·ã«å€ãã
ã³éçµå£æ¶²å€ãŸãã¯æžæ¿å€ã®å€åœ¢ã§åºå®åžéå€ã
æ°Žæ§ããã¯ã«ãéæ¯æ§ææ©æº¶åªãå«ãçš®ã ã®è¬åŠ
çã«èš±å®¹ã§ããäžæŽ»æ§æ äœãšçµã¿åãããŠãã
ããäžè¬ã«ãããã®ååç©ã¯çš®ã ã®å€åœ¢äžã«å šçµ
æç©ã®çŽ0.5ãçŽ90ééïŒ ã®ç¯å²ã®æ¿åºŠæ°ŽçŽ ã§å©
çšãããã 次ã®å®æœäŸã¯åã«äŸç€ºã®ç®çã§æ ããããŠã
ããæ¬çºæãéå®ãããã®ãšè§£éãããããšã¯ãª
ãããããŠæ¬çºæã®å€ãã®å€åã¯æ¬çºæã®ç²Ÿç¥ãŸ
ãã¯ç¯å²ããé¢ããããšãªãã«å¯èœãªããšã§ã
ãã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
âãšãªã¹ããã€ã·ã³ïŒ¡ïŒïŒ ïŒâã«ç¶æããã¯ãããã«ã ïŒäžã®ïŒâãžã
ãããšãªã¹ããã€ã·ã³A50ïœïŒ68ããªã¢ã«ïŒãšïŒ
âã¡ããã·ãããã³64mlïŒ680ããªã¢ã«ïŒã®æžæ¿
液ãæ¹æããªãããããã«ããªãžã³å¡©é žå¡©12ïœ
ïŒ102ããªã¢ã«ïŒãå°éã¥ã€å ããããã®æ··åç©ã
宀枩ã§å€éãæ¹æãããã®åŸæ°ŽïŒäžã«æ³šãã§
6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿æŽã
ããã¯ãããã«ã çžãåé¢ãç空ã§ä¹Ÿç¥ãããŸã§
æ¿çž®ãããåºåœ¢æ®çç©ãã¢ã»ãã³ïŒæ°Žæ··å溶åªã«
溶解ãã6Nã®å¡©é žã§PHã3.6ã«èª¿æŽããã宀枩ã§
ïŒæéæ¹æåŸãã®æº¶æ¶²ãå¡©åã¡ãã¬ã³ïŒæ°Žæ··å溶
åªäžã«æ³šãã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã
調æŽãããææ©çžãåé¢ããŠç¡«é žãããªãŠã ã§ä¹Ÿ
ç¥ãç空äžã«æ¿çž®ããŠç¡è²ã®åºäœãåŸãããã®æ®
çç©ããšã¿ããŒã«âæ°Žæ··å溶åªããåçµæ¶ããã
ãšã«ãã粟補ããŠ38ïœãåŸããèç¹217âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.2ïŒ6HãïœïŒã3.3ïŒ3HãïœïŒ
ããã³3.4ã5.1ïŒ13HãïœïŒppmã«åžåã瀺ããã å çŽ åæïŒC40H73NO13ãšããŠïŒ èšç®å€ïŒïŒ£ã61.91ïŒïŒšã9.48ïŒïŒ®ã1.81 å®æž¬å€ïŒïŒ£ã61.97ïŒïŒšã9.20ïŒïŒ®ã1.75 ãαã22 DïŒCHCl3ãïŒïŒ ïœïŒïœïŒïŒâ36.1ã å®æœäŸ é žç¡æ°Žç©ã䜿çšãã2â²âãšã¹ãã«ã®äžè¬ç補é
æ¹æ³ ïŒâã«ç¶æããïŒâãžãããâ11ïŒ12ââã€
ãœããããªãã³âãšãªã¹ããã€ã·ã³A1åœéå«æ
ã®å¡©åã¡ãã¬ã³æº¶æ¶²ïŒ10ïŒ ïŒã«é©åœãªé žç¡æ°Žç©
1.5åœéã滎äžããŠå ããããã®åå¿æ··åç©ã宀
æž©ãŸã§æããŠ12æéãã®æž©åºŠã§æ¹æããããã®åŸ
åå¿æ··åç©ãæ°ŽïŒå¡©åã¡ãã¬ã³æ··å溶åªäžã«æ³š
ãã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿æŽ
ãããææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠ
ç空æ¿çž®ãããçæç©ã¯ã¢ã»ãã³âæ°Žæ··å溶åªã
ãåçµæ¶ããã äžèšæ¹æ³ã䜿çšããŠæ¬¡ã®ååç©ã補é ããã ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³â
2â²âã¢ã»ãã«âãšãªã¹ããã€ã·ã³ïŒ¡ èç¹182ã184âãNMRã¹ãã¯ãã«ïŒCDCl3ïŒ
ã¯0.8ã1.3ïŒ41HãïœïŒã1.4ïŒ6HãïœïŒã2.1ïŒ6Hã
ïœïŒã3.3ïŒ3HãïœïŒããã³3.4ã5.1ïŒ12HãïœïŒ
ppmã«åžåããã ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³â
2â²âããããªãã«âãšãªã¹ããã€ã·ã³ïŒ¡ èç¹189ã191âãNMRã¹ãã¯ãã«ïŒCDCl3ïŒ
ã¯0.8ã1.3ïŒ46HãïœïŒã1.4ïŒ6HãïœïŒã2.1ã2.3
ïŒ2HãïœïŒã3.4ïŒ3HãïœïŒããã³3.4ã5.1ïŒ12Hã
ïœïŒppmã«åžåã瀺ããã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âïŒãšãã«ã¹ã¯ã·ãã«ïŒâãšãªã¹ããã€ã·ã³
 ïŒâã«å·åŽããå¡©åã¡ãã¬ã³25mläžïŒâãžãã
ãâ11ïŒ12ââã€ãœããããªãã³âãšãªã¹ãã
ã€ã·ã³A1.82ïœïŒ2.5ããªã¢ã«ïŒå«æ溶液ã«ãšãã«
ã¹ã¯ã·ãã«ã¯ããªã0.92mlïŒ6.5ããªã¢ã«ïŒã滎
äžããŠå ãããã®æ··åç©ãïŒâã§ïŒæéæ¹æã
ããåå¿æ··åç©ãå¡©åã¡ãã¬ã³ïŒæ°Žæ··å溶åªäžã«
泚ãã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿
æŽãããææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ã
ãŠç空æ¿çž®ãããæ®ççæç©ã¯ã¢ã»ãã³ïŒæ°Žæ··å
溶åªããåçµæ¶ããŠ1.0ïœãåŸããèç¹169ã170
âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.2ïŒ6HãïœïŒã2.6ïŒ4HãïœïŒ
ã
3.3ïŒ3HãïœïŒã4.1ïŒ2HãïœïŒããã³4.4ã5.1
ïŒ10HãïœïŒppmã«åžåã瀺ããã åæ§ã®æ¹æ³ã§ïŒâãžãããâ11ïŒ12ââã€ãœ
ããããªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ãšé©åœãªé žå¡©
åç©ãšããåºçºããŠïŒâãžãããâ11ïŒ12ââ
ã€ãœããããªãã³â2â²âã¢ã»ãã«âãšãªã¹ããã€
ã·ã³ïŒ¡ããã³ïŒâãžãããâ11ïŒ12ââã€ãœã
ãããªãã³â2â²âããããªãã«âãšãªã¹ããã€ã·
ã³ïŒ¡ã補é ããã å®æœäŸ ïŒâãžãããâ4â³âãšãâãšãªã¹ããã€ã·ã³ïŒ¡ 4â³âããªãã·â4â³âãªããœâãšãªã¹ããã€ã·ã³
A50ïœïŒ68.3ããªã¢ã«ïŒãšã©ããŒããã±ã«250ïœ
ã®ã¹ã©ãªãŒãåæå§95.2æ°å§ïŒ1400psiïŒã®æ°ŽçŽ
é°å²æ°äžã«å®€æž©ã§å€éãæ¯ãšãããããã®æ··åç©
ãã¹ãŒããŒã»ã«ãéããŠéãã液ãç空äžã«
æ¿çž®ããŠç¡è²ã®åºäœãåŸãããããã¢ã»ãã³ïŒæ°Ž
æ··å溶åªããåçµæ¶ããããšã«ãã粟補ããŠ40ïœ
ãåŸããèç¹139ã143âã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â4â³âãšãâãšãªã¹ããã€ã·ã³ïŒ¡ ïŒâã«ç¶æããïŒâãžãããâ4â³âãšãâãšãª
ã¹ããã€ã·ã³A65ïœïŒ88.3ããªã¢ã«ïŒãšïŒâã¡ã
ãã·ãããã³82.6mlïŒ883ããªã¢ã«ïŒå«æã®ã¯ã
ããã«ã 溶液ïŒ700mlïŒã«ããªãžã³å¡©é žå¡©15.3ïœ
ïŒ132ããªã¢ã«ïŒãå°éã¥ã€å ããããã®åå¿æ··å
ç©ã宀枩ãŸã§æããŠããã®æž©åºŠã§å€éãæ¹æã
ãããã®æ··åç©ãæ°Žã®äžã«æ³šãã§6Nã®æ°Žé žåã
ããªãŠã 溶液ã§PHã9.5ã«èª¿æŽãããææ©çžãå
é¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠç空æ¿çž®ãç¡è²ã®
åºäœãåŸãããã®æ®çåºäœãã¢ã»ãã³ïŒæ°Žæ··å溶
åªã«æº¶è§£ããŠ6Nã®å¡©é žã§PHã3.5ã«èª¿æŽãããçŽ
ïŒæéåŸã溶液ã®PHã6Nã®æ°Žé žåãããªãŠã 溶
液ã§6.2ã«äžããŠæšçã§åŠçãéããã液ã
ã¯ãããã«ã ïŒæ°Žæ··å溶åªäžã«æ³šãã6Nã®æ°Žé ž
åãããªãŠã 溶液ã§PHãããã«9.5ãŸã§äžããã
ææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠæ¿çž®ã
ããæ®çåºäœããšã¿ããŒã«ïŒæ°Žæ··å溶åªããåçµ
æ¶ããŠçæç©ã50ïœåŸããèç¹214ã217âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.2ïŒ6HãïœïŒã3.3ïŒ3HãïœïŒ
ããã³3.5ã5.1ïŒ13HãïœïŒppmã«åžåã瀺ããã å çŽ åæïŒC40H73NO13ãšããŠïŒ èšç®å€ïŒïŒ£ã61.91ïŒïŒšã9.48ïŒïŒ®ã1.81 å®æž¬å€ïŒïŒ£ã61.96ïŒïŒšã9.51ïŒïŒ®ã1.86 C22 DïŒCHCl3ãïŒïŒ ïœïŒïœïŒïŒâ35.9ã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âã¢ã»ãã«â4â³âãšãâãšãªã¹ããã€ã·ã³
 å¡©åã¡ãã¬ã³12mläžïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³â4â³âãšãâãšãªã¹ããã€ã·
ã³A1.25ïœïŒ1.61ããªã¢ã«ïŒå«æ溶液ã«ç¡æ°Žé ¢é ž
0.167mlïŒ1.77ããªã¢ã«ïŒãå ããçããæ··åç©
ã宀枩ã§å€éãæ¹æãããåå¿æ··åç©ãæ°Žã®äžã«
泚ã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿æŽ
ãããææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠ
ç空äžã«æ¿çž®ãç¡è²ã®åºäœãåŸããæ®çç©ããžãš
ãã«ãšãŒãã«ããåçµæ¶ããŠ1.0ïœãåŸããèç¹
138ã142âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.0ïŒ3HãïœïŒã2.2ïŒ6HãïœïŒ
ããã³3.4ïŒ3HãïœïŒppmã«åžåã瀺ããã åæ§ã®æ¹æ³ã§ãïŒâãžãããâ11ïŒ12ââã€
ãœããããªãã³â4â³âãšãâãšãªã¹ããã€ã·ã³
A1.3ïœãç¡æ°Žããããªã³é ž0.236mlãšããåºçºã
ãŠïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âããããªãã«â4â³âãšãâãšãªã¹ããã€ã·
ã³A0.90ïœãåŸããèç¹128ã133âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.3ïŒ6HãïœïŒããã³3.4ïŒ3Hã
ïœïŒppmã«åžåã瀺ããã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âïŒãšãã«ã¹ã¯ã·ãã«ïŒâ4â³âãšãâãšãªã¹
ããã€ã·ã³ïŒ¡ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â4â³âãšãâãšãªã¹ããã€ã·ã³A1.2ïœïŒ1.55ããª
ã¢ã«ïŒãšçé žæ°ŽçŽ ãããªãŠã 800mgå«æã¢ã»ãã³
溶液ïŒ12mlïŒã«ãšãã«ã¹ã¯ã·ãã«ã¯ããªã0.242
mlïŒ1.7ããªã¢ã«ïŒãå ãããã®æ··åç©ã宀枩ã§
å€éãæ¹æãããè¿œå ã®ãšãã«ã¹ã¯ã·ãã«ã¯ããª
ã66.2ÎŒïŒ0.465ããªã¢ã«ïŒãå ããŠãã®åå¿ã
ïŒæéç¶ããããã®åŸæ··åç©ãå¡©åã¡ãã¬ã³ïŒæ°Ž
æ··å溶åªäžã«æ³šãã ãææ©çžãåé¢ãç¡«é žãããª
ãŠã ã§ä¹Ÿç¥ããŠæ¿çž®ãçæç©0.90ïœãåŸãã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.3ïŒ6HãïœïŒã2.6ïŒ4HãïœïŒ
ã
3.4ïŒ3HãïœïŒããã³4.1ïŒ2HãïœïŒppmã«åžåã
瀺ããã åæ§ã®æ¹æ³ã§ããšãã«ã¹ã¯ã·ãã«ã¯ããªããå¡©
åã¢ã»ãã«ããã³å¡©åããããªãã«ã§çœ®ãæãã
ããšã«ããããããïŒâãžãããâ11ïŒ12ââ
ã€ãœããããªãã³â2â²âã¢ã»ãã«â4â³âãšãâãš
ãªã¹ããã€ã·ã³ïŒ¡ããã³ïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³â2â²âããããªãã«â4â³â
ãšãâãšãªã¹ããã€ã·ã³ïŒ¡ã補é ããã
æ¯èŒããŠæ¬çºæååç©ããã³ãææã«ããã
ãå¹æãæããããšã¯æããã§ããã ãããã®æ°èŠååç©ãçäœå ã§äœ¿çšãããå Ž
åããããã¯çµå£çã«ãŸãã¯éçµå£çã«ããšãã°
ç®äžæ³šå°ãçèå 泚å°ã«ããäžæ¥ãããçŽ25mgïŒ
KgïŒäœéïŒãçŽ200mgïŒKgã®éã§æäžããããé©
åœãªæè¬ç¯å²ã¯äžæ¥ãããçŽ150mgïŒKgãçŽ200
mgïŒKgã§ããã泚å°å€ã«é©ããããã¯ã«ã¯æ°Žãç
çé£å¡©æ¶²ããããŠç³ç匵液ããã³ãªã³ã²ã«æ¶²ã®ã
ããªæ°Žæ§ã®ãã®ã§ãããããããã¯æ€ç©ããã®è
èªæ²¹ïŒç¶¿å®æ²¹ãããŒãããæ²¹ãã³ãŒã³æ²¹ãããŸ
æ²¹ïŒããžã¡ãã«ã¹ã«ããã·ãããã³è£œå€ã®æ²»çå¹
åã劚ãããŸã䜿çšããã容éãå²åã§éæ¯æ§ã§
ããä»ã®éæ°Žæ§ããã¯ã«é¡ïŒã°ãªã»ãªã³ãããã
ã¬ã³ã°ãªã³ãŒã«ããœã«ãããŒã«ïŒã®ãããªéæ°Žæ§
ã®ãã®ã§ãããããã«æäžåã«æ¶²å€ãçšæé補ã
ãã®ã«é©ããçµæç©ãæå©ã«äœãããããã®ãã
ãªçµæç©ã¯æ¶²ç¶åžéå€ïŒããšãã°ãããã¬ã³ã°ãª
ã³ãŒã«ããžãšãã«ã«ãŒãããŒããã°ãªã»ãªã³ããœ
ã«ãããŒã«çïŒãç·©è¡å€ããã¢ã«ãŠããããŒãŒã
å±æ麻é è¬ããã³ææã®å»è¬æ§è³ªãä»äžãããã
ã®ç¡æ©å¡©ãå«ãã§ããŠãããããããã®ååç©ã¯
ãŸãã«ãã»ã«å€ãé å€ãããŒã³ãžå€ããããŒã
å€ã也ç¥è£œå€ãæžæ¿å€ã液å€ããšãªãã·ã«å€ãã
ã³éçµå£æ¶²å€ãŸãã¯æžæ¿å€ã®å€åœ¢ã§åºå®åžéå€ã
æ°Žæ§ããã¯ã«ãéæ¯æ§ææ©æº¶åªãå«ãçš®ã ã®è¬åŠ
çã«èš±å®¹ã§ããäžæŽ»æ§æ äœãšçµã¿åãããŠãã
ããäžè¬ã«ãããã®ååç©ã¯çš®ã ã®å€åœ¢äžã«å šçµ
æç©ã®çŽ0.5ãçŽ90ééïŒ ã®ç¯å²ã®æ¿åºŠæ°ŽçŽ ã§å©
çšãããã 次ã®å®æœäŸã¯åã«äŸç€ºã®ç®çã§æ ããããŠã
ããæ¬çºæãéå®ãããã®ãšè§£éãããããšã¯ãª
ãããããŠæ¬çºæã®å€ãã®å€åã¯æ¬çºæã®ç²Ÿç¥ãŸ
ãã¯ç¯å²ããé¢ããããšãªãã«å¯èœãªããšã§ã
ãã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
âãšãªã¹ããã€ã·ã³ïŒ¡ïŒïŒ ïŒâã«ç¶æããã¯ãããã«ã ïŒäžã®ïŒâãžã
ãããšãªã¹ããã€ã·ã³A50ïœïŒ68ããªã¢ã«ïŒãšïŒ
âã¡ããã·ãããã³64mlïŒ680ããªã¢ã«ïŒã®æžæ¿
液ãæ¹æããªãããããã«ããªãžã³å¡©é žå¡©12ïœ
ïŒ102ããªã¢ã«ïŒãå°éã¥ã€å ããããã®æ··åç©ã
宀枩ã§å€éãæ¹æãããã®åŸæ°ŽïŒäžã«æ³šãã§
6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿æŽã
ããã¯ãããã«ã çžãåé¢ãç空ã§ä¹Ÿç¥ãããŸã§
æ¿çž®ãããåºåœ¢æ®çç©ãã¢ã»ãã³ïŒæ°Žæ··å溶åªã«
溶解ãã6Nã®å¡©é žã§PHã3.6ã«èª¿æŽããã宀枩ã§
ïŒæéæ¹æåŸãã®æº¶æ¶²ãå¡©åã¡ãã¬ã³ïŒæ°Žæ··å溶
åªäžã«æ³šãã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã
調æŽãããææ©çžãåé¢ããŠç¡«é žãããªãŠã ã§ä¹Ÿ
ç¥ãç空äžã«æ¿çž®ããŠç¡è²ã®åºäœãåŸãããã®æ®
çç©ããšã¿ããŒã«âæ°Žæ··å溶åªããåçµæ¶ããã
ãšã«ãã粟補ããŠ38ïœãåŸããèç¹217âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.2ïŒ6HãïœïŒã3.3ïŒ3HãïœïŒ
ããã³3.4ã5.1ïŒ13HãïœïŒppmã«åžåã瀺ããã å çŽ åæïŒC40H73NO13ãšããŠïŒ èšç®å€ïŒïŒ£ã61.91ïŒïŒšã9.48ïŒïŒ®ã1.81 å®æž¬å€ïŒïŒ£ã61.97ïŒïŒšã9.20ïŒïŒ®ã1.75 ãαã22 DïŒCHCl3ãïŒïŒ ïœïŒïœïŒïŒâ36.1ã å®æœäŸ é žç¡æ°Žç©ã䜿çšãã2â²âãšã¹ãã«ã®äžè¬ç補é
æ¹æ³ ïŒâã«ç¶æããïŒâãžãããâ11ïŒ12ââã€
ãœããããªãã³âãšãªã¹ããã€ã·ã³A1åœéå«æ
ã®å¡©åã¡ãã¬ã³æº¶æ¶²ïŒ10ïŒ ïŒã«é©åœãªé žç¡æ°Žç©
1.5åœéã滎äžããŠå ããããã®åå¿æ··åç©ã宀
æž©ãŸã§æããŠ12æéãã®æž©åºŠã§æ¹æããããã®åŸ
åå¿æ··åç©ãæ°ŽïŒå¡©åã¡ãã¬ã³æ··å溶åªäžã«æ³š
ãã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿æŽ
ãããææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠ
ç空æ¿çž®ãããçæç©ã¯ã¢ã»ãã³âæ°Žæ··å溶åªã
ãåçµæ¶ããã äžèšæ¹æ³ã䜿çšããŠæ¬¡ã®ååç©ã補é ããã ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³â
2â²âã¢ã»ãã«âãšãªã¹ããã€ã·ã³ïŒ¡ èç¹182ã184âãNMRã¹ãã¯ãã«ïŒCDCl3ïŒ
ã¯0.8ã1.3ïŒ41HãïœïŒã1.4ïŒ6HãïœïŒã2.1ïŒ6Hã
ïœïŒã3.3ïŒ3HãïœïŒããã³3.4ã5.1ïŒ12HãïœïŒ
ppmã«åžåããã ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³â
2â²âããããªãã«âãšãªã¹ããã€ã·ã³ïŒ¡ èç¹189ã191âãNMRã¹ãã¯ãã«ïŒCDCl3ïŒ
ã¯0.8ã1.3ïŒ46HãïœïŒã1.4ïŒ6HãïœïŒã2.1ã2.3
ïŒ2HãïœïŒã3.4ïŒ3HãïœïŒããã³3.4ã5.1ïŒ12Hã
ïœïŒppmã«åžåã瀺ããã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âïŒãšãã«ã¹ã¯ã·ãã«ïŒâãšãªã¹ããã€ã·ã³
 ïŒâã«å·åŽããå¡©åã¡ãã¬ã³25mläžïŒâãžãã
ãâ11ïŒ12ââã€ãœããããªãã³âãšãªã¹ãã
ã€ã·ã³A1.82ïœïŒ2.5ããªã¢ã«ïŒå«æ溶液ã«ãšãã«
ã¹ã¯ã·ãã«ã¯ããªã0.92mlïŒ6.5ããªã¢ã«ïŒã滎
äžããŠå ãããã®æ··åç©ãïŒâã§ïŒæéæ¹æã
ããåå¿æ··åç©ãå¡©åã¡ãã¬ã³ïŒæ°Žæ··å溶åªäžã«
泚ãã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿
æŽãããææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ã
ãŠç空æ¿çž®ãããæ®ççæç©ã¯ã¢ã»ãã³ïŒæ°Žæ··å
溶åªããåçµæ¶ããŠ1.0ïœãåŸããèç¹169ã170
âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.2ïŒ6HãïœïŒã2.6ïŒ4HãïœïŒ
ã
3.3ïŒ3HãïœïŒã4.1ïŒ2HãïœïŒããã³4.4ã5.1
ïŒ10HãïœïŒppmã«åžåã瀺ããã åæ§ã®æ¹æ³ã§ïŒâãžãããâ11ïŒ12ââã€ãœ
ããããªãã³âãšãªã¹ããã€ã·ã³ïŒ¡ãšé©åœãªé žå¡©
åç©ãšããåºçºããŠïŒâãžãããâ11ïŒ12ââ
ã€ãœããããªãã³â2â²âã¢ã»ãã«âãšãªã¹ããã€
ã·ã³ïŒ¡ããã³ïŒâãžãããâ11ïŒ12ââã€ãœã
ãããªãã³â2â²âããããªãã«âãšãªã¹ããã€ã·
ã³ïŒ¡ã補é ããã å®æœäŸ ïŒâãžãããâ4â³âãšãâãšãªã¹ããã€ã·ã³ïŒ¡ 4â³âããªãã·â4â³âãªããœâãšãªã¹ããã€ã·ã³
A50ïœïŒ68.3ããªã¢ã«ïŒãšã©ããŒããã±ã«250ïœ
ã®ã¹ã©ãªãŒãåæå§95.2æ°å§ïŒ1400psiïŒã®æ°ŽçŽ
é°å²æ°äžã«å®€æž©ã§å€éãæ¯ãšãããããã®æ··åç©
ãã¹ãŒããŒã»ã«ãéããŠéãã液ãç空äžã«
æ¿çž®ããŠç¡è²ã®åºäœãåŸãããããã¢ã»ãã³ïŒæ°Ž
æ··å溶åªããåçµæ¶ããããšã«ãã粟補ããŠ40ïœ
ãåŸããèç¹139ã143âã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â4â³âãšãâãšãªã¹ããã€ã·ã³ïŒ¡ ïŒâã«ç¶æããïŒâãžãããâ4â³âãšãâãšãª
ã¹ããã€ã·ã³A65ïœïŒ88.3ããªã¢ã«ïŒãšïŒâã¡ã
ãã·ãããã³82.6mlïŒ883ããªã¢ã«ïŒå«æã®ã¯ã
ããã«ã 溶液ïŒ700mlïŒã«ããªãžã³å¡©é žå¡©15.3ïœ
ïŒ132ããªã¢ã«ïŒãå°éã¥ã€å ããããã®åå¿æ··å
ç©ã宀枩ãŸã§æããŠããã®æž©åºŠã§å€éãæ¹æã
ãããã®æ··åç©ãæ°Žã®äžã«æ³šãã§6Nã®æ°Žé žåã
ããªãŠã 溶液ã§PHã9.5ã«èª¿æŽãããææ©çžãå
é¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠç空æ¿çž®ãç¡è²ã®
åºäœãåŸãããã®æ®çåºäœãã¢ã»ãã³ïŒæ°Žæ··å溶
åªã«æº¶è§£ããŠ6Nã®å¡©é žã§PHã3.5ã«èª¿æŽãããçŽ
ïŒæéåŸã溶液ã®PHã6Nã®æ°Žé žåãããªãŠã 溶
液ã§6.2ã«äžããŠæšçã§åŠçãéããã液ã
ã¯ãããã«ã ïŒæ°Žæ··å溶åªäžã«æ³šãã6Nã®æ°Žé ž
åãããªãŠã 溶液ã§PHãããã«9.5ãŸã§äžããã
ææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠæ¿çž®ã
ããæ®çåºäœããšã¿ããŒã«ïŒæ°Žæ··å溶åªããåçµ
æ¶ããŠçæç©ã50ïœåŸããèç¹214ã217âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.2ïŒ6HãïœïŒã3.3ïŒ3HãïœïŒ
ããã³3.5ã5.1ïŒ13HãïœïŒppmã«åžåã瀺ããã å çŽ åæïŒC40H73NO13ãšããŠïŒ èšç®å€ïŒïŒ£ã61.91ïŒïŒšã9.48ïŒïŒ®ã1.81 å®æž¬å€ïŒïŒ£ã61.96ïŒïŒšã9.51ïŒïŒ®ã1.86 C22 DïŒCHCl3ãïŒïŒ ïœïŒïœïŒïŒâ35.9ã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âã¢ã»ãã«â4â³âãšãâãšãªã¹ããã€ã·ã³
 å¡©åã¡ãã¬ã³12mläžïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³â4â³âãšãâãšãªã¹ããã€ã·
ã³A1.25ïœïŒ1.61ããªã¢ã«ïŒå«æ溶液ã«ç¡æ°Žé ¢é ž
0.167mlïŒ1.77ããªã¢ã«ïŒãå ããçããæ··åç©
ã宀枩ã§å€éãæ¹æãããåå¿æ··åç©ãæ°Žã®äžã«
泚ã6Nã®æ°Žé žåãããªãŠã 溶液ã§PHã9.5ã«èª¿æŽ
ãããææ©çžãåé¢ãç¡«é žãããªãŠã ã§ä¹Ÿç¥ããŠ
ç空äžã«æ¿çž®ãç¡è²ã®åºäœãåŸããæ®çç©ããžãš
ãã«ãšãŒãã«ããåçµæ¶ããŠ1.0ïœãåŸããèç¹
138ã142âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.0ïŒ3HãïœïŒã2.2ïŒ6HãïœïŒ
ããã³3.4ïŒ3HãïœïŒppmã«åžåã瀺ããã åæ§ã®æ¹æ³ã§ãïŒâãžãããâ11ïŒ12ââã€
ãœããããªãã³â4â³âãšãâãšãªã¹ããã€ã·ã³
A1.3ïœãç¡æ°Žããããªã³é ž0.236mlãšããåºçºã
ãŠïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âããããªãã«â4â³âãšãâãšãªã¹ããã€ã·
ã³A0.90ïœãåŸããèç¹128ã133âã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.3ïŒ6HãïœïŒããã³3.4ïŒ3Hã
ïœïŒppmã«åžåã瀺ããã å®æœäŸ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â2â²âïŒãšãã«ã¹ã¯ã·ãã«ïŒâ4â³âãšãâãšãªã¹
ããã€ã·ã³ïŒ¡ ïŒâãžãããâ11ïŒ12ââã€ãœããããªãã³
â4â³âãšãâãšãªã¹ããã€ã·ã³A1.2ïœïŒ1.55ããª
ã¢ã«ïŒãšçé žæ°ŽçŽ ãããªãŠã 800mgå«æã¢ã»ãã³
溶液ïŒ12mlïŒã«ãšãã«ã¹ã¯ã·ãã«ã¯ããªã0.242
mlïŒ1.7ããªã¢ã«ïŒãå ãããã®æ··åç©ã宀枩ã§
å€éãæ¹æãããè¿œå ã®ãšãã«ã¹ã¯ã·ãã«ã¯ããª
ã66.2ÎŒïŒ0.465ããªã¢ã«ïŒãå ããŠãã®åå¿ã
ïŒæéç¶ããããã®åŸæ··åç©ãå¡©åã¡ãã¬ã³ïŒæ°Ž
æ··å溶åªäžã«æ³šãã ãææ©çžãåé¢ãç¡«é žãããª
ãŠã ã§ä¹Ÿç¥ããŠæ¿çž®ãçæç©0.90ïœãåŸãã NMRã¹ãã¯ãã«ïŒCDCl3ïŒã¯0.8ã1.3ïŒ41Hã
ïœïŒã1.4ïŒ6HãïœïŒã2.3ïŒ6HãïœïŒã2.6ïŒ4HãïœïŒ
ã
3.4ïŒ3HãïœïŒããã³4.1ïŒ2HãïœïŒppmã«åžåã
瀺ããã åæ§ã®æ¹æ³ã§ããšãã«ã¹ã¯ã·ãã«ã¯ããªããå¡©
åã¢ã»ãã«ããã³å¡©åããããªãã«ã§çœ®ãæãã
ããšã«ããããããïŒâãžãããâ11ïŒ12ââ
ã€ãœããããªãã³â2â²âã¢ã»ãã«â4â³âãšãâãš
ãªã¹ããã€ã·ã³ïŒ¡ããã³ïŒâãžãããâ11ïŒ12â
âã€ãœããããªãã³â2â²âããããªãã«â4â³â
ãšãâãšãªã¹ããã€ã·ã³ïŒ¡ã補é ããã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ æ¬¡åŒã®ãã¯ãã©ã€ããããªã矀ããéžã°ãã
ååç©ããã³ãã®å»è¬ãšããŠé©åœãªé žä»å å¡©ã ãåŒã ïŒåŒäžãã¯æ°ŽçŽ ãççŽ æ°ïŒãïŒã®ã¢ã«ã«ãã€ã«
ããã³ãšãã«ã¹ã¯ã·ãã«ãããªã矀ããéžã°ã
ããïŒ ïŒ ïŒ²ãæ°ŽçŽ ã§ãããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã«èš
èŒã®ååç©ã ïŒ C4â³âããããã·ã«åºãã¢ã¯ã·ã¢ã«çµåããŠ
ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒ C4â³âããããã·ã«åºããšã«ããªã¢ã«çµåã
ãŠããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒ æ¬¡åŒã®ååç©åã¯ãã®å»è¬ãšããŠé©åœãªé žä»
å å¡©ãšè¬åŠçã«èš±å®¹ã§ããæ äœãšãããªãæèçµ
æç©ã ãåŒã ïŒåŒäžãã¯æ°ŽçŽ ãççŽ æ°ïŒãïŒã®ã¢ã«ã«ãã€ã«
ããã³ãšãã«ã¹ã¯ã·ãã«ãããªã矀ããéžã°ã
ããïŒ
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/353,548 US4382086A (en) | 1982-03-01 | 1982-03-01 | 9-Dihydro-11,12-ketal derivatives of erythromycin A and epi-erythromycin A |
US353548 | 2003-01-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS58159500A JPS58159500A (ja) | 1983-09-21 |
JPH0142275B2 true JPH0142275B2 (ja) | 1989-09-11 |
Family
ID=23389607
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP58033682A Granted JPS58159500A (ja) | 1982-03-01 | 1983-03-01 | ãšãªã¹ããã€ã·ã³ïœããã³ãšãâãšãªã¹ããã€ã·ã³ïœã®ïŒâãžãããâïŒïŒïŒïŒïŒâã±ã¿âã«èªå°äœ |
Country Status (8)
Country | Link |
---|---|
US (1) | US4382086A (ja) |
EP (1) | EP0087916B1 (ja) |
JP (1) | JPS58159500A (ja) |
DE (1) | DE3361453D1 (ja) |
DK (1) | DK159853C (ja) |
GR (1) | GR77921B (ja) |
IE (1) | IE54431B1 (ja) |
YU (1) | YU42841B (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8421429D0 (en) * | 1984-08-23 | 1984-09-26 | Beecham Group Plc | Chemical compounds |
EP0184921A3 (en) * | 1984-12-08 | 1986-10-29 | Beecham Group Plc | Erythromycin derivatives |
PT82162B (en) | 1985-03-12 | 1987-08-06 | Beecham Group Plc | Chemical compounds |
US4640910A (en) * | 1985-11-12 | 1987-02-03 | Abbott Laboratories | Erythromycin A silylated compounds and method of use |
US4681872A (en) * | 1985-11-12 | 1987-07-21 | Abbott Laboratories | Erythromycin A 11,12-carbonate and method of use |
WO1992006991A1 (fr) * | 1990-10-15 | 1992-04-30 | Taisho Pharmaceutical Co., Ltd. | Erythromycine modifiee en 2' ou derive de cette substance |
AU2003211113B2 (en) * | 2002-02-15 | 2007-08-09 | Merckle Gmbh | Antibiotic conjugates |
NZ535354A (en) | 2002-02-15 | 2008-01-31 | Merckle Gmbh | Conjugates of biologically active compounds, methods for their preparation and use, formulation and pharmaceutical applications thereof |
US20060099660A1 (en) * | 2002-02-15 | 2006-05-11 | Synovo Gmbh | Conjugates of biologically active compounds, methods for their preparation and use, formulation and pharmaceutical applications thereof |
WO2004019879A2 (en) * | 2002-08-29 | 2004-03-11 | Kosan Biosciences, Inc. | Motilide compounds |
US7211568B2 (en) * | 2003-12-18 | 2007-05-01 | Kosan Biosciences Incorporated | 9-Desoxoerythromycin compounds as prokinetic agents |
CN101228171A (zh) * | 2005-07-26 | 2008-07-23 | é»å åæéå ¬åž | äœäžº5-èæ°§åé ¶åç¯å æ°§é ¶æå¶åçå¡å¯éåªåäžæ°®èååç©ç倧ç¯å é ¯å¶èç© |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3884904A (en) * | 1973-06-21 | 1975-05-20 | Abbott Lab | 11-Substituted erythromycin B derivatives |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2653899A (en) * | 1952-04-14 | 1953-09-29 | Lilly Co Eli | Erythromycin, its salts, and method of preparation |
US3417077A (en) * | 1966-05-16 | 1968-12-17 | Lilly Co Eli | Erythromycin derivative and process for the preparation thereof |
US3884903A (en) * | 1973-06-21 | 1975-05-20 | Abbott Lab | 4{41 -Deoxy-4{41 -oxoerythromycin B derivatives |
US4150220A (en) * | 1977-02-04 | 1979-04-17 | Pfizer Inc. | Semi-synthetic 4"-erythromycin A derivatives |
-
1982
- 1982-03-01 US US06/353,548 patent/US4382086A/en not_active Expired - Lifetime
-
1983
- 1983-02-23 DE DE8383300937T patent/DE3361453D1/de not_active Expired
- 1983-02-23 GR GR70583A patent/GR77921B/el unknown
- 1983-02-23 EP EP83300937A patent/EP0087916B1/en not_active Expired
- 1983-02-25 YU YU459/83A patent/YU42841B/xx unknown
- 1983-02-28 IE IE410/83A patent/IE54431B1/en not_active IP Right Cessation
- 1983-02-28 DK DK096983A patent/DK159853C/da not_active IP Right Cessation
- 1983-03-01 JP JP58033682A patent/JPS58159500A/ja active Granted
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3884904A (en) * | 1973-06-21 | 1975-05-20 | Abbott Lab | 11-Substituted erythromycin B derivatives |
Also Published As
Publication number | Publication date |
---|---|
JPS58159500A (ja) | 1983-09-21 |
EP0087916B1 (en) | 1985-12-11 |
IE54431B1 (en) | 1989-10-11 |
DK96983A (da) | 1983-09-02 |
IE830410L (en) | 1983-09-01 |
DK96983D0 (da) | 1983-02-28 |
EP0087916A1 (en) | 1983-09-07 |
DE3361453D1 (en) | 1986-01-23 |
DK159853C (da) | 1991-05-13 |
YU45983A (en) | 1986-02-28 |
DK159853B (da) | 1990-12-17 |
US4382086A (en) | 1983-05-03 |
YU42841B (en) | 1988-12-31 |
GR77921B (ja) | 1984-09-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Letavic et al. | Synthesis and activity of a novel class of tribasic macrocyclic antibiotics: the triamilides | |
EP0087905B1 (en) | 4"-epi erythromycin a and derivatives thereof as useful antibacterial agents | |
JPH0142275B2 (ja) | ||
JPS5827800B2 (ja) | æ°èŠæèå€ | |
DE69022845T2 (de) | Erythromycinderivate. | |
EP0132944A1 (en) | Antibacterial homoerythromycin A derivatives and intermediates therefor | |
CA1323026C (en) | Antibacterial 9-deoxo-9a-allyl and propargyl-9a-aza- 9a-homoerythromycin a derivatives | |
JPS5931795A (ja) | ïœïœã®ïœâïŒïŒâ修食èªå°äœ | |
US4585759A (en) | Antibacterial derivatives of a neutral macrolide | |
SU1020004A3 (ru) | СпПÑПб пПлÑÑеМО пÑПОзвПЎМÑÑ ÐŸÐ»ÐµÐ°ÐœÐŽÐŸÐŒÐžÑОМа | |
EP0114486B1 (en) | Alkylation of oleandomycin | |
SU927122A3 (ru) | СпПÑПб пПлÑÑеМО пÑПОзвПЎМÑÑ 4"-ЎеПкÑО-4"-аЌОМП-ÑÑОÑÑПЌОÑОМа РОлО ÐžÑ ÑПлей | |
EP0345627B1 (en) | 9-R-azacyclic erythromycin antibiotics | |
US4363803A (en) | 3",4"-Oxyallylene erythromycin and oleandomycin, composition and method of use | |
US4413119A (en) | Semi-synthetic macrolides | |
KR820001218B1 (ko) | ë°í©ì± 4"-ìë¯žë ž-ì¬ë ìë ë§ìŽì ì ë첎ì ì ì¡°ë°©ë² | |
US4098994A (en) | Sulfamide derivatives of 4 -deoxy-oleandomycin | |
DK158473B (da) | Cycliske ethere af 9-deoxo-9a-aza-9a-homoerythromycin a og dettes 4ae-epimer, forbindelser til anvendelse som udgangsmateriale ved deres fremstilling, farmaceutiske praeparater indeholdende de cycliske ethere og anvendelse af de cycliske ethere til fremstilling af laegemidler |