JP2002121416A - Liquid composition - Google Patents
Liquid compositionInfo
- Publication number
- JP2002121416A JP2002121416A JP2000315975A JP2000315975A JP2002121416A JP 2002121416 A JP2002121416 A JP 2002121416A JP 2000315975 A JP2000315975 A JP 2000315975A JP 2000315975 A JP2000315975 A JP 2000315975A JP 2002121416 A JP2002121416 A JP 2002121416A
- Authority
- JP
- Japan
- Prior art keywords
- liquid composition
- aqueous medium
- cyanine dye
- oxygen
- concentration
- 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.)
- Granted
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 47
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 claims abstract description 48
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 42
- 239000001301 oxygen Substances 0.000 claims abstract description 42
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 42
- 239000012736 aqueous medium Substances 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 150000002500 ions Chemical class 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000008213 purified water Substances 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 4
- 239000000975 dye Substances 0.000 description 43
- -1 1-methylpentyl Chemical group 0.000 description 10
- 239000003814 drug Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000005587 bubbling Effects 0.000 description 3
- 210000004027 cell Anatomy 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
- 229940079593 drug Drugs 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229940123973 Oxygen scavenger Drugs 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002316 cosmetic surgery Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- CSTRPYAGFNTOEQ-MGMRMFRLSA-N (2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;octadecanoic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O.CCCCCCCCCCCCCCCCCC(O)=O CSTRPYAGFNTOEQ-MGMRMFRLSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- FKFUHAJJKUCVRF-UHFFFAOYSA-N 2-[3,5-bis(3-heptyl-4-methyl-1,3-thiazol-3-ium-2-yl)penta-2,4-dienylidene]-3-heptyl-4-methyl-1,3-thiazole Chemical compound CCCCCCCN1C(C)=CSC1=CC=C(C1=[N+](C(C)=CS1)CCCCCCC)C=CC1=[N+](CCCCCCC)C(C)=CS1 FKFUHAJJKUCVRF-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 206010073306 Exposure to radiation Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 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
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 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
- 241001465754 Metazoa Species 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229910052787 antimony Inorganic materials 0.000 description 1
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 229940079920 digestives acid preparations Drugs 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- VZFDRQUWHOVFCA-UHFFFAOYSA-L disodium;2-sulfanylbutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(S)C([O-])=O VZFDRQUWHOVFCA-UHFFFAOYSA-L 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-M periodate Chemical compound [O-]I(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- GNBVPFITFYNRCN-UHFFFAOYSA-M sodium thioglycolate Chemical compound [Na+].[O-]C(=O)CS GNBVPFITFYNRCN-UHFFFAOYSA-M 0.000 description 1
- 229940046307 sodium thioglycolate Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
(57)【要約】
【課題】 特定のシアニン色素を含有する、安定にし
て取扱い易い液状組成物を提供することを課題とする。
【解決手段】特定のシアニン色素と、そのシアニン色素
を溶解する水性媒体とを含んでなり、溶存酸素の濃度が
その水性媒体の常温常圧の大気環境下における酸素濃度
を下回る液状組成物と、特定のシアニン色素を水性媒体
に溶解する工程と、該水性媒体をしてその常温常圧の大
気環境下における酸素濃度を下回らせる工程とを経由す
る液状組成物の製造方法を提供することによって前記の
課題を解決するものである。(57) [Problem] To provide a stable and easy-to-handle liquid composition containing a specific cyanine dye. A liquid composition comprising a specific cyanine dye and an aqueous medium that dissolves the cyanine dye, wherein the concentration of dissolved oxygen is lower than the oxygen concentration of the aqueous medium in an atmospheric environment at normal temperature and normal pressure; Dissolving a specific cyanine dye in an aqueous medium, and providing a method for producing a liquid composition through a step of lowering the oxygen concentration of the aqueous medium in an atmospheric environment at normal temperature and normal pressure by providing the method. It is intended to solve the problem.
Description
【０００１】[0001]
【発明の属する技術分野】本発明は有機色素化合物を含
有する組成物に関するものであり、詳細には、シアニン
色素を含有する安定な液状組成物に関するものである。TECHNICAL FIELD The present invention relates to a composition containing an organic dye compound, and more particularly to a stable liquid composition containing a cyanine dye.
【０００２】[0002]
【従来の技術】疾病を惹起する根本的な原因としては、
微生物感染、化学物質への接触、放射線への被爆、生活
環境、生活習慣、老化、遺伝的要素などが挙げられる
が、斯かる病因に対する生体の反応は様々である。例え
ば、微生物感染の場合、微生物が侵入したすべての生体
が感染症を惹起するわけではなく、また、感染症の治療
に際して、同様の治療を受けている患者同士であって
も、回復の状況や副作用が有意に異なることがある。そ
の原因の一つとして、生体の活力が細胞レベルで低下し
ていることが考えられ、生体の活力が細胞レベルで低下
していると、当然のことながら、健康の回復が遅れた
り、薬剤の副作用が強く顕現することとなる。細胞賦活
剤は、斯かる患者を対象として、必要に応じて、他の薬
剤と併用することによって、病因に対する生体の抵抗力
や回復力を細胞レベルで昂進するための薬剤である。細
胞賦活剤としては、現在、クロロフィル製剤、色素製
剤、核酸製剤、アミノ酸製剤、動植物の抽出物などが用
いられており、このうち、色素製剤は、低用量で著効を
発揮し、しかも、作用が穏やかで、長期間連用しても重
篤な副作用を惹起しないことから、熱傷及び難治性皮膚
潰瘍を中心に１９４０年代から用いられている。2. Description of the Related Art The underlying causes of disease are:
Examples include microbial infection, exposure to chemical substances, exposure to radiation, living environment, lifestyle, aging, genetic factors, and the like, and the response of the living body to such etiology varies. For example, in the case of microbial infection, not all living organisms invaded by microbes cause an infectious disease, and when treating infectious diseases, the recovery status and Side effects can be significantly different. One possible cause is that the vitality of the living body is reduced at the cellular level.If the vitality of the living body is reduced at the cellular level, the recovery of health is naturally delayed, Side effects will be strongly manifested. The cell activator is a drug for such a patient, which is used in combination with another drug, if necessary, to enhance the resistance or recovery of the living body to the etiology at the cellular level. Currently, chlorophyll preparations, pigment preparations, nucleic acid preparations, amino acid preparations, extracts of animals and plants, and the like are used as cell activators. Since it is mild and does not cause serious side effects even after long-term use, it has been used mainly for burns and intractable skin ulcers since the 1940s.
【０００３】色素製剤は、対象となる疾患や症状などに
応じて、皮内、筋肉内又は静脈内へ注射投与される。現
在、色素製剤はシアニン色素を含有する乾燥注射剤の形
態のものだけが市販されているが、液状製剤が入手でき
ないのは、シアニン色素が水性媒体中で不安定であるこ
とによるとされている。シアニン色素の乾燥注射剤は、
水性媒体におけるシアニン色素の溶解度が比較的小さい
ことから、使用に先立って、臨床現場において所定の濃
度の溶液に調製するのに手間が掛かるという問題があっ
た。[0003] Dye preparations are injected intradermally, intramuscularly, or intravenously depending on the disease or condition to be treated. At present, pigment preparations are only commercially available in the form of dry injections containing cyanine dyes, but liquid preparations are not available because cyanine dyes are unstable in aqueous media. . Dry injection of cyanine dye
Since the solubility of the cyanine dye in the aqueous medium is relatively small, there is a problem that it takes time to prepare a solution having a predetermined concentration at a clinical site before use.
【０００４】[0004]
【発明が解決しようとする課題】斯かる状況に鑑み、こ
の発明の課題は、シアニン色素を含有する安定な液状組
成物を提供することにある。In view of such circumstances, an object of the present invention is to provide a stable liquid composition containing a cyanine dye.
【０００５】[0005]
【課題を解決するための手段】この課題を解決すべく、
本発明者が鋭意研究し、検索したところ、水性媒体にお
いてシアニン色素が不安定であるのは、共存する酸素が
原因であることを突き止めた。そこで、本発明者がシア
ニン色素の液状組成物における酸素濃度に着目し、溶存
酸素の濃度が相違する種々の液状組成物を調製するとと
もに、これらを一定時間放置した後、残存するシアニン
色素を測定したところ、溶存酸素の濃度が水性媒体の常
温常圧の大気環境下における酸素濃度を下回る液状組成
物においては、シアニン色素が分解し難く、比較的長期
間に亙って安定に存在することを見出した。Means for Solving the Problems In order to solve this problem,
The present inventor has conducted extensive research and searched, and found that the instability of the cyanine dye in the aqueous medium is due to coexisting oxygen. Therefore, the present inventor focused on the oxygen concentration in the liquid composition of the cyanine dye, prepared various liquid compositions having different dissolved oxygen concentrations, left these for a certain period of time, and then measured the remaining cyanine dye. As a result, it was found that in a liquid composition in which the concentration of dissolved oxygen is lower than the oxygen concentration in an aqueous medium at normal temperature and normal pressure in an atmospheric environment, the cyanine dye is hardly decomposed and stably exists for a relatively long period of time. I found it.
【０００６】すなわち、この発明は、上記の課題を、特
定のシアニン色素と、そのシアニン色素を溶解する水性
媒体とを含んでなり、溶存酸素の濃度がその水性媒体の
常温常圧の大気環境下における酸素濃度を下回る液状組
成物を提供することによって解決するものである。That is, the present invention solves the above-mentioned problems by including a specific cyanine dye and an aqueous medium in which the cyanine dye is dissolved, wherein the concentration of dissolved oxygen in an atmospheric environment at normal temperature and normal pressure of the aqueous medium. The problem is solved by providing a liquid composition having an oxygen concentration lower than that in the above.
【０００７】さらに、この発明は、上記の課題を、特定
のシアニン色素を水性媒体に溶解する工程と、該水性媒
体をしてその常温常圧の大気環境下における酸素濃度を
下回らせる工程とを経由する液状組成物の製造方法を提
供することによって解決するものである。Further, the present invention solves the above-mentioned problems by providing a step of dissolving a specific cyanine dye in an aqueous medium and a step of using the aqueous medium to lower the oxygen concentration in an atmospheric environment at normal temperature and normal pressure. This problem is solved by providing a method for producing a liquid composition via a liquid.
【０００８】[0008]
【発明の実施の形態】既述のとおり、この発明は、一般
式１で表されるシアニン色素（以下、単に「シアニン色
素」と言うことがある。）と、シアニン色素を溶解する
水性媒体とを含んでなり、溶存酸素の濃度がその水性媒
体の常温常圧の大気環境下における酸素濃度を下回る液
状組成物に関するものである。DESCRIPTION OF THE PREFERRED EMBODIMENTS As described above, the present invention relates to a cyanine dye represented by the general formula 1 (hereinafter sometimes simply referred to as "cyanine dye") and an aqueous medium in which the cyanine dye is dissolved. And a liquid composition wherein the concentration of dissolved oxygen is lower than the oxygen concentration of the aqueous medium in an atmospheric environment at normal temperature and normal pressure.
【０００９】[0009]
【化２】 Embedded image
【００１０】一般式１において、Ｒは脂肪族炭化水素基
を表す。Ｒにおける脂肪族炭化水素基としては、通常、
炭素数が１乃至１２であるものが選択され、個々の脂肪
族炭化水素基としては、例えば、メチル基、エチル基、
プロピル基、イソプロピル基、ブチル基、イソブチル
基、ｓｅｃ−ブチル基、ｔｅｒｔ−ブチル基、ペンチル
基、イソペンチル基、ｔｅｒｔ−ペンチル基、１−メチ
ルペンチル基、２−メチルペンチル基、ヘキシル基、イ
ソヘキシル基、５−メチルヘキシル基、ヘプチル基、オ
クチル基、ノニル基、デシル基、ウンデシル基、ドデシ
ル基などが挙げられる。一般式１におけるＸ-は適宜の
対イオンであり、通常、例えば、弗素イオン、塩素イオ
ン、臭素イオン、沃素イオン、過塩素酸イオン、過沃素
酸イオン、六弗化燐酸イオン、六弗化アンチモン酸イオ
ン、六弗化錫酸イオン、燐酸イオン、硼弗化水素イオ
ン、四弗硼素酸イオンなどの無機酸アニオンや、チアシ
アン酸イオン、ベンゼンスルホン酸イオン、ナフタレン
スルホン酸イオン、ナフタレンジスルホン酸イオン、ｐ
−トルエンスルホン酸イオン、アルキルスルホン酸イオ
ン、ベンゼンカルボン酸イオン、アルキルカルボン酸イ
オン、トリハロアルキルカルボン酸イオン、アルキル硫
酸イオン、トリハロアルキル硫酸イオン、ニコチン酸イ
オン、アスパラギン酸イオンなどの有機酸アニオンから
選択される。このうち、注射剤として用いられる液状組
成物におけるシアニン色素としては、Ｒの炭素数が４乃
至１０、とりわけ、炭素数６乃至８のものが細胞膜への
親和性が大きいので特に好ましい。また、対イオンが沃
素イオンであるシアニン色素は、沃素イオンが生体内で
殺菌作用を発揮する特徴がある。一般式１で表されるシ
アニン色素の具体例としては、例えば、化学式１乃至化
学式３で表されるものが挙げられ、これらは、いずれ
も、この発明において極めて有利に用いることができ
る。In the general formula 1, R represents an aliphatic hydrocarbon group. As the aliphatic hydrocarbon group for R,
Those having 1 to 12 carbon atoms are selected, and as each aliphatic hydrocarbon group, for example, a methyl group, an ethyl group,
Propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, 1-methylpentyl, 2-methylpentyl, hexyl, isohexyl , 5-methylhexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the like. X − in the general formula 1 is an appropriate counter ion, and is usually, for example, a fluoride ion, a chloride ion, a bromine ion, an iodine ion, a perchlorate ion, a periodate ion, a hexafluorophosphate ion, an antimony hexafluoride ion. Inorganic acid anions such as acid ion, hexafluorostannate ion, phosphate ion, borofluoride ion, tetrafluoroborate ion, thiocyanate ion, benzenesulfonic acid ion, naphthalenesulfonic acid ion, naphthalene disulfonic acid ion, p
-Select from organic acid anions such as toluenesulfonate, alkylsulfonate, benzenecarboxylate, alkylcarboxylate, trihaloalkylcarboxylate, alkylsulfate, trihaloalkylsulfate, nicotinate, and aspartate. Is done. Among them, as the cyanine dye in the liquid composition used as an injection, those having R of 4 to 10, especially 6 to 8, are particularly preferred because of their high affinity for cell membranes. Cyanine dyes whose counter ion is iodine ion are characterized in that iodine ion exerts a bactericidal action in a living body. Specific examples of the cyanine dye represented by the general formula 1 include, for example, those represented by the chemical formulas 1 to 3, and all of them can be used very advantageously in the present invention.
【００１１】[0011]
【化３】 Embedded image
【００１２】[0012]
【化４】 Embedded image
【００１３】[0013]
【化５】 Embedded image
【００１４】この発明でいう水性媒体とは、水を必須の
要素とし、必要に応じて、これに、例えば、メタノー
ル、エタノール、プロパノール、イソプロパノールなど
のアルコール類、アセトンなどのケトン類、ジエチルエ
ーテルなどのエーテル類、ジメチルスルホキシドなどの
含硫化合物をはじめとする親水性有機溶剤の１又は複数
を配合してなる水性媒体一般を意味する。この発明によ
る注射剤における水性溶剤としては、注射用精製水を単
独で用いるか、あるいは、注射用精製水と、例えば、エ
タノール、プロパノール、イソプロパノール、ジエチル
エーテル、ジメチルスルホキシドなどの生理学的に許容
される親水性有機溶剤との混液を用いるのが望ましい。The term "aqueous medium" as used in the present invention refers to water as an essential element and, if necessary, alcohols such as methanol, ethanol, propanol and isopropanol, ketones such as acetone, diethyl ether and the like. Means an aqueous medium in which one or more hydrophilic organic solvents including ethers and sulfur-containing compounds such as dimethyl sulfoxide are blended. As the aqueous solvent in the injection according to the present invention, purified water for injection is used alone, or purified water for injection and a physiologically acceptable water such as ethanol, propanol, isopropanol, diethyl ether, dimethyl sulfoxide and the like. It is desirable to use a liquid mixture with a hydrophilic organic solvent.
【００１５】この発明でいう液状組成物とは、斯かる水
性媒体に一般式１で表されるシアニン色素を１又は複数
溶解してなり、かつ、水性媒体に溶存する酸素の濃度が
その常温常圧の大気環境下における酸素濃度を下回る範
囲、通常、８ｐｐｍ以下、望ましくは、０．４ｐｐｍ以
下、さらに望ましくは、０．１ｐｐｍ以下に設定され
る。斯かる酸素濃度の液状組成物は、調製又は保存に際
して、自然光や人工光などの環境光へ露光しても、シア
ニン色素が分解し難い。とりわけ、酸素濃度が０．１ｐ
ｐｍ以下である液状組成物は、環境光を遮断しない条件
で長期間保存しても、酸素が遮断されているかぎり、シ
アニン色素がほとんど分解しない。[0015] The liquid composition according to the present invention is obtained by dissolving one or a plurality of cyanine dyes represented by the general formula 1 in such an aqueous medium, and adjusting the concentration of oxygen dissolved in the aqueous medium to the normal temperature and normal temperature. The pressure is set to a range lower than the oxygen concentration in the atmospheric environment, usually 8 ppm or less, preferably 0.4 ppm or less, more preferably 0.1 ppm or less. In the liquid composition having such an oxygen concentration, the cyanine dye is hardly decomposed even when exposed to environmental light such as natural light or artificial light during preparation or storage. Especially, oxygen concentration is 0.1p
Even if the liquid composition having a pm or less is stored for a long time under the condition that the ambient light is not blocked, the cyanine dye hardly decomposes as long as the oxygen is blocked.
【００１６】斯かる液状組成物は、通常、シアニン色素
を水性媒体に溶解する工程と、該水性媒体をしてその常
温常圧の大気環境下における酸素濃度を下回らせる工程
とを経由するこの発明による製造方法により調製するこ
とができる。シアニン色素を水性媒体に溶解するには、
例えば、所定の量のシアニン色素を適量の水性媒体へ添
加し、必要に応じて、加熱・攪拌しながら溶解させた
後、必要に応じて、シアニン色素の濃度が所定のレベル
になるまで水性媒体を追加する。この発明による液状組
成物は、この発明の目的を逸脱しない範囲で、シアニン
色素とともに、用途に応じたそれ以外の薬剤、細胞賦活
剤に汎用されるビタミン類、アミノ酸類、浸透圧調節
剤、緩衝剤、さらには、脱酸素剤などを配合することを
妨げない。The liquid composition of the present invention generally comprises a step of dissolving a cyanine dye in an aqueous medium, and a step of using the aqueous medium to lower the oxygen concentration in an atmospheric environment at normal temperature and normal pressure. Can be prepared. To dissolve the cyanine dye in an aqueous medium,
For example, a predetermined amount of a cyanine dye is added to an appropriate amount of an aqueous medium, and if necessary, dissolved while heating and stirring.If necessary, the concentration of the cyanine dye in the aqueous medium is reduced to a predetermined level. Add. The liquid composition according to the present invention may contain, together with the cyanine dye, other drugs according to the intended use, vitamins, amino acids, osmotic pressure regulators, and buffers commonly used in cell activators, without departing from the purpose of the present invention. It does not hinder the incorporation of an agent and further an oxygen scavenger.
【００１７】水性媒体をしてその常温常圧の大気環境下
における酸素濃度を溶液における酸素濃度を下回らせる
には、例えば、液状組成物を減圧下で調製し、保存する
か、液状組成物に溶存する酸素を別の気体で置換する
か、あるいは、液状組成物を脱酸素剤へ接触させる方法
が好適である。液状組成物に溶解する酸素を別の気体で
置換するには、液状組成物中で、例えば、窒素などの比
較的不活性な気体か、あるいは、ネオン、アルゴン、ク
リプトン、キセノンなどの希ガスをバブリングさせれば
よい。脱酸素剤を用いて酸素濃度を下げるには、液状組
成物へ、例えば、Ｌ−アスコルビン酸、Ｌ−アスコルビ
ン酸ステアリン酸エステル、亜硫酸ナトリウム、亜硫酸
水素ナトリウム、アルファチオグリセリン、エデト酸ナ
トリウム、塩酸システイン、クエン酸、大豆レシチン、
チオグリコール酸ナトウム、チオリンゴ酸ナトリウム、
ピロ亜硫酸ナトリウム、ブチルヒドロキシアニソールな
どを適量添加すればよい。これらの方法は、シアニン色
素を含有する液状組成物へ適用しても、シアニン色素を
溶解する前の水性媒体へ適用してもよい。In order to use an aqueous medium to lower the oxygen concentration of the solution in an atmospheric environment at normal temperature and normal pressure to lower than the oxygen concentration in the solution, for example, a liquid composition is prepared under reduced pressure and stored or stored. A preferred method is to replace dissolved oxygen with another gas, or to contact the liquid composition with an oxygen scavenger. To replace oxygen dissolved in the liquid composition with another gas, for example, a relatively inert gas such as nitrogen or a rare gas such as neon, argon, krypton, or xenon in the liquid composition. What is necessary is to bubble. In order to lower the oxygen concentration using a deoxidizer, the liquid composition may be added to, for example, L-ascorbic acid, L-ascorbic acid stearate, sodium sulfite, sodium bisulfite, alpha thioglycerin, sodium edetate, cysteine hydrochloride. , Citric acid, soy lecithin,
Sodium thioglycolate, sodium thiomalate,
An appropriate amount of sodium pyrosulfite, butylhydroxyanisole, or the like may be added. These methods may be applied to a liquid composition containing a cyanine dye, or may be applied to an aqueous medium before dissolving the cyanine dye.
【００１８】斯くして得られた液状組成物は、酸素を遮
断し得る、用途に応じた適宜の容器へ封入した状態で保
存される。容器の材質としては、原理上、液状組成物を
保持することができ、かつ、酸素を実質的に遮断し得る
ものであるかぎり、特に制限がない。用途にもよるけれ
ども、通常、ガラスアンプル、バイアル瓶などの容器へ
液状組成物を分注し、封止した後、高圧滅菌などにより
滅菌する。The liquid composition thus obtained is stored in a state in which it can be sealed off in an appropriate container depending on the use, which can block oxygen. In principle, the material of the container is not particularly limited as long as it can hold the liquid composition and can substantially block oxygen. Although it depends on the application, the liquid composition is usually dispensed into containers such as glass ampules and vials, sealed, and then sterilized by high-pressure sterilization or the like.
【００１９】この発明による液状組成物の使用方法につ
いて説明すると、この発明による液状組成物は、自然
光、人工光などの環境光へ長期間露光してもシアニン色
素が分解し難いことから、医療分野をはじめとする種々
の分野で極めて有用である。最も重要な用途は医療の分
野にあり、この発明の液状組成物による注射剤は、外
科、成形外科、形成外科、放射線科、内科、神経科、神
経内科、小児科、呼吸器科、産婦人科、耳鼻咽喉科、皮
膚科、泌尿器科、眼科、麻酔科、歯科などの医療分野に
おいて、単独又は他の治療剤、予防剤と併用して、生体
における免疫系、造血系、内分泌系、循環器系、消化器
系、神経系を細胞レベルで賦活する。さらに、この発明
による注射剤は、生体膜における脂質成分が酸化される
のを抑制する作用がある。医療の分野以外の分野におけ
る用途としては、化学及び分析化学の分野において、シ
アニン色素の収量や分析精度の向上にも著明な効果を発
揮する。なお、医療分野において、この発明による液状
組成物を注射剤として用いる場合、用法、用量は従来公
知のものに準じて設定する。The method of using the liquid composition according to the present invention will be described. The liquid composition according to the present invention hardly decomposes a cyanine dye even after long-term exposure to ambient light such as natural light or artificial light. And other various fields. The most important application is in the field of medicine, and the injection with the liquid composition of the present invention is used for surgery, plastic surgery, plastic surgery, radiology, internal medicine, neurology, neurology, pediatrics, respiratory medicine, obstetrics and gynecology. In the medical fields such as otorhinolaryngology, dermatology, urology, ophthalmology, anesthesiology, and dentistry, alone or in combination with other therapeutic and prophylactic agents, the immune system, hematopoietic system, endocrine system, and circulatory system in vivo Activates the system, digestive system, and nervous system at the cellular level. Further, the injection according to the present invention has an action of suppressing oxidation of lipid components in a biological membrane. As applications in fields other than the field of medicine, in the fields of chemistry and analytical chemistry, the present invention exerts a remarkable effect on the improvement of the yield and analysis accuracy of cyanine dyes. In the medical field, when the liquid composition according to the present invention is used as an injection, the usage and dosage are set according to those conventionally known.
【００２０】以下、この発明の実施の形態につき、実施
例に沿って説明する。Hereinafter, embodiments of the present invention will be described with reference to examples.
【００２１】[0021]
【実施例】〈液状組成物〉注射用精製水２００ｇにグル
コース１５ｇを溶解してなる溶液と、注射用精製水８５
ｇに化学式３で表されるプラトニン類１５ｍｇを溶解し
てなる溶液とを混合して液状組成物となし、溶存する酸
素の濃度が約０．１ｐｐｍになるまで窒素ガスをバブリ
ングし、褐色アンプルに１ｍｌずつ分注し、窒素気流下
でアンプルを封止した後、高圧滅菌した。定法により測
定したところ、本例の液状組成物における酸素濃度は
０．０９７ｐｐｍであった。EXAMPLES <Liquid composition> A solution obtained by dissolving 15 g of glucose in 200 g of purified water for injection, and 85 g of purified water for injection
g of a solution prepared by dissolving 15 mg of a platonin represented by the chemical formula 3 to form a liquid composition, and bubbling nitrogen gas until the concentration of dissolved oxygen becomes about 0.1 ppm. After dispensing 1 ml each, the ampule was sealed under a nitrogen stream, and then autoclaved. As measured by a conventional method, the oxygen concentration in the liquid composition of this example was 0.097 ppm.
【００２２】比較のために、バブリング時間を短かくす
るか、バブリングを省略することによって、溶存酸素の
濃度が０．４７ｐｐｍ、０．４９ｐｐｍ又は８．８ｐｐ
ｍである液状組成物を調製した。以上の液状組成物につ
き、容器内で酸素を遮断しつつ、環境光を遮蔽しない条
件で２５日間放置する一方、定期的に液状組成物をサン
プリングし、高速液体クロマトグラフィーにより残存す
るシアニン色素の量を測定した。結果を図１に示す。For comparison, by shortening the bubbling time or omitting the bubbling, the dissolved oxygen concentration can be reduced to 0.47 ppm, 0.49 ppm or 8.8 pp.
m was prepared. The above liquid composition was left for 25 days under the condition that the ambient light was not shielded while blocking oxygen in the container, while periodically sampling the liquid composition and determining the amount of the remaining cyanine dye by high performance liquid chromatography. Was measured. The results are shown in FIG.
【００２３】図１の結果は、溶液状のシアニン色素を分
解させる主因が溶存酸素であり、水性媒体をしてその常
温常圧の大気環境下における酸素濃度を下回らせること
によって、シアニン色素の残存率（％）、すなわち、配
合したシアニン色素に対する残存シアニン色素の比率を
改善し得ることを物語っている。図１の結果に見られる
とおり、シアニン色素の残存率は溶存酸素の濃度が低下
するにしたがって改善され、０．１ｐｐｍ以下の酸素濃
度では、実に、２５日間放置しても、容器内で酸素が遮
断されているかぎり、シアニン色素が全く分解しなかっ
た。FIG. 1 shows that dissolved oxygen is the main cause of decomposition of the cyanine dye in solution, and the residual oxygen of the cyanine dye is reduced by lowering the oxygen concentration in an aqueous medium under an atmospheric environment at normal temperature and normal pressure. This indicates that the ratio (%), that is, the ratio of the residual cyanine dye to the blended cyanine dye can be improved. As can be seen from the results in FIG. 1, the residual ratio of the cyanine dye is improved as the concentration of dissolved oxygen is reduced. At an oxygen concentration of 0.1 ppm or less, even if the container is left standing for 25 days, oxygen remains in the container. No cyanine dye was degraded as long as it was blocked.
【００２４】[0024]
【発明の効果】以上説明したとおり、この発明は、シア
ニン色素が水性媒体において分解する主因が溶存酸素で
あるという従来未知の独自の知見に基づくものである。
安定にして取扱い易いこの発明の液状組成物は、医療分
野における注射剤としての用途に加えて、化学及び分析
化学の分野において、シアニン色素の収量や分析精度を
改善するうえで極めて有用である。As described above, the present invention is based on a previously unknown and original finding that dissolved oxygen is the main cause of the decomposition of a cyanine dye in an aqueous medium.
The liquid composition of the present invention, which is stable and easy to handle, is extremely useful for improving the yield and analysis accuracy of cyanine dyes in the fields of chemistry and analytical chemistry, in addition to its use as an injection in the medical field.
【００２５】斯くも顕著な効果を奏するこの発明は、斯
界に貢献すること誠に多大な、意義のある発明であると
言える。The present invention having such remarkable effects can be said to be a significant invention which greatly contributes to the art.
【図１】酸素濃度が異なる液状組成物におけるシアニン
色素の残存率の変化を経時的に示す図である。FIG. 1 is a graph showing changes in the residual ratio of a cyanine dye in liquid compositions having different oxygen concentrations over time.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｐ 43/00 １０７ Ａ６１Ｐ 43/00 １０７ Ｆターム(参考） 4C076 AA12 BB11 CC19 CC26 DD21 DD67 FF12 FF36 FF51 4C086 AA01 AA02 BC82 MA02 MA05 MA17 MA66 NA03 NA14 ZA89 ZB22 ZC19 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 7 Identification symbol FI theme coat ゛ (Reference) A61P 43/00 107 A61P 43/00 107 F term (Reference) 4C076 AA12 BB11 CC19 CC26 DD21 DD67 FF12 FF36 FF51 4C086 AA01 AA02 BC82 MA02 MA05 MA17 MA66 NA03 NA14 ZA89 ZB22 ZC19
Claims (6)
のシアニン色素を溶解する水性媒体とを含んでなり、溶
存酸素の濃度がその水性媒体の常温常圧の大気環境下に
おける酸素濃度を下回る液状組成物。 【化1】 一般式１において、Ｒは脂肪族炭化水素基を、また、Ｘ
-は適宜の対イオンを表す。Claims: 1. An aqueous medium comprising a cyanine dye represented by the general formula 1 and an aqueous medium dissolving the cyanine dye, wherein the concentration of dissolved oxygen is the oxygen concentration of the aqueous medium in an atmospheric environment at normal temperature and normal pressure. Less than liquid composition. [Formula 1] In the general formula 1, R represents an aliphatic hydrocarbon group;
- represents a suitable counterion.
オンである請求項１に記載の液状組成物。2. The liquid composition according to claim 1, wherein the counter ion X − in the general formula 1 is an iodine ion.
に記載の液状組成物。3. The method according to claim 1, wherein the aqueous medium is purified water.
3. The liquid composition according to item 1.
る請求項１、２又は３に記載の液状組成物。4. The liquid composition according to claim 1, wherein the concentration of dissolved oxygen is 0.4 ppm or less.
に記載の液状組成物。5. The method according to claim 1, 2, 3, or 4 as an injection.
3. The liquid composition according to item 1.
媒体に溶解する工程と、該水性媒体をしてその常温常圧
の大気環境下における酸素濃度を下回らせる工程とを経
由する請求項１乃至５のいずれかに記載の液状組成物の
製造方法。6. A method comprising the steps of: dissolving a cyanine dye represented by the general formula 1 in an aqueous medium; and reducing the oxygen concentration of the aqueous medium in an atmospheric environment at normal temperature and normal pressure. 6. The method for producing a liquid composition according to any one of 1 to 5.
Priority Applications (2)
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|---|---|---|---|
| JP2000315975A JP5013325B2 (en) | 2000-10-16 | 2000-10-16 | Liquid composition |
| KR1020010063186A KR20020030022A (en) | 2000-10-16 | 2001-10-13 | Liquid composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000315975A JP5013325B2 (en) | 2000-10-16 | 2000-10-16 | Liquid composition |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002121416A true JP2002121416A (en) | 2002-04-23 |
| JP2002121416A5 JP2002121416A5 (en) | 2007-11-29 |
| JP5013325B2 JP5013325B2 (en) | 2012-08-29 |
Family
ID=18794989
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000315975A Expired - Lifetime JP5013325B2 (en) | 2000-10-16 | 2000-10-16 | Liquid composition |
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| Country | Link |
|---|---|
| JP (1) | JP5013325B2 (en) |
| KR (1) | KR20020030022A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010087306A1 (en) * | 2009-01-29 | 2010-08-05 | 株式会社林原生物化学研究所 | Anti-neurodegenerative disease agent |
| WO2010087313A1 (en) * | 2009-01-29 | 2010-08-05 | 株式会社林原生物化学研究所 | Neurite elongation stimulator |
| WO2010087315A1 (en) * | 2009-01-29 | 2010-08-05 | 株式会社林原生物化学研究所 | Anti-alzheimer’s disease agent |
| JP2016180058A (en) * | 2015-03-24 | 2016-10-13 | 株式会社日本触媒 | Method for storing or using composition comprising oxocarbon compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06227950A (en) * | 1993-02-04 | 1994-08-16 | Medical Heaa:Kk | Hair growing and trichogenous system |
| JP2000186040A (en) * | 1998-12-21 | 2000-07-04 | Hayashibara Biochem Lab Inc | Anti-HIV infection agent |
-
2000
- 2000-10-16 JP JP2000315975A patent/JP5013325B2/en not_active Expired - Lifetime
-
2001
- 2001-10-13 KR KR1020010063186A patent/KR20020030022A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06227950A (en) * | 1993-02-04 | 1994-08-16 | Medical Heaa:Kk | Hair growing and trichogenous system |
| JP2000186040A (en) * | 1998-12-21 | 2000-07-04 | Hayashibara Biochem Lab Inc | Anti-HIV infection agent |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010087306A1 (en) * | 2009-01-29 | 2010-08-05 | 株式会社林原生物化学研究所 | Anti-neurodegenerative disease agent |
| WO2010087313A1 (en) * | 2009-01-29 | 2010-08-05 | 株式会社林原生物化学研究所 | Neurite elongation stimulator |
| WO2010087315A1 (en) * | 2009-01-29 | 2010-08-05 | 株式会社林原生物化学研究所 | Anti-alzheimer’s disease agent |
| JP5591720B2 (en) * | 2009-01-29 | 2014-09-17 | 株式会社林原 | Anti-neurodegenerative disease agent |
| JP2016180058A (en) * | 2015-03-24 | 2016-10-13 | 株式会社日本触媒 | Method for storing or using composition comprising oxocarbon compound |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20020030022A (en) | 2002-04-22 |
| JP5013325B2 (en) | 2012-08-29 |
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