JP2017066054A - Aqueous external composition comprising iodine-based bactericidal component - Google Patents
Aqueous external composition comprising iodine-based bactericidal component Download PDFInfo
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- JP2017066054A JP2017066054A JP2015190307A JP2015190307A JP2017066054A JP 2017066054 A JP2017066054 A JP 2017066054A JP 2015190307 A JP2015190307 A JP 2015190307A JP 2015190307 A JP2015190307 A JP 2015190307A JP 2017066054 A JP2017066054 A JP 2017066054A
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- iodine
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- aqueous
- aqueous external
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- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 title claims abstract description 87
- 239000011630 iodine Substances 0.000 title claims abstract description 86
- 229910052740 iodine Inorganic materials 0.000 title claims abstract description 86
- 239000000203 mixture Substances 0.000 title claims abstract description 82
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 22
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims abstract description 96
- 150000001875 compounds Chemical class 0.000 claims abstract description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 239000007788 liquid Substances 0.000 claims description 23
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 13
- 239000004094 surface-active agent Substances 0.000 claims description 9
- 210000000214 mouth Anatomy 0.000 claims description 8
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 claims description 5
- 229920000153 Povidone-iodine Polymers 0.000 claims description 5
- 229960003237 betaine Drugs 0.000 claims description 5
- 150000003904 phospholipids Chemical class 0.000 claims description 5
- 229960001621 povidone-iodine Drugs 0.000 claims description 5
- 239000012669 liquid formulation Substances 0.000 claims description 4
- 229920000847 nonoxynol Polymers 0.000 claims description 4
- LHDMBYWDIBGTAR-UHFFFAOYSA-N phenyl hypoiodite Chemical compound IOC1=CC=CC=C1 LHDMBYWDIBGTAR-UHFFFAOYSA-N 0.000 claims description 3
- 210000002200 mouth mucosa Anatomy 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 20
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 230000008021 deposition Effects 0.000 abstract description 3
- 238000001556 precipitation Methods 0.000 description 31
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 19
- -1 iodide ions Chemical class 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 238000002156 mixing Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 230000001954 sterilising effect Effects 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 6
- 230000003381 solubilizing effect Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- YADZBEISHVCBSJ-UHFFFAOYSA-N [I].OCC(O)CO Chemical compound [I].OCC(O)CO YADZBEISHVCBSJ-UHFFFAOYSA-N 0.000 description 4
- 239000002280 amphoteric surfactant Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000008344 egg yolk phospholipid Substances 0.000 description 3
- 229940068998 egg yolk phospholipid Drugs 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- ASKIVFGGGGIGKH-UHFFFAOYSA-N 2,3-dihydroxypropyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(O)CO ASKIVFGGGGIGKH-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 210000004393 laryngeal mucosa Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 229910001414 potassium ion Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5alpha)-cholestan-3beta-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- UYZQWKKNVBJVOF-UHFFFAOYSA-N 1-decoxytetradecane Chemical compound CCCCCCCCCCCCCCOCCCCCCCCCC UYZQWKKNVBJVOF-UHFFFAOYSA-N 0.000 description 1
- JWKSQNWLEIABLH-UHFFFAOYSA-N 1-octan-2-yloxydodecane Chemical compound CCCCCCCCCCCCOC(C)CCCCCC JWKSQNWLEIABLH-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- GQQNRZHWHWHOLI-UHFFFAOYSA-N 11-(2-decyltetradecoxymethyl)tricosane Chemical compound CCCCCCCCCCCCC(CCCCCCCCCC)COCC(CCCCCCCCCC)CCCCCCCCCCCC GQQNRZHWHWHOLI-UHFFFAOYSA-N 0.000 description 1
- XPALGXXLALUMLE-UHFFFAOYSA-N 2-(dimethylamino)tetradecanoic acid Chemical compound CCCCCCCCCCCCC(N(C)C)C(O)=O XPALGXXLALUMLE-UHFFFAOYSA-N 0.000 description 1
- ZVUNTIMPQCQCAQ-UHFFFAOYSA-N 2-dodecanoyloxyethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCC ZVUNTIMPQCQCAQ-UHFFFAOYSA-N 0.000 description 1
- IKVCSHRLYCDSFD-UHFFFAOYSA-N 2-hexadecanoyloxyethyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCCCCCC IKVCSHRLYCDSFD-UHFFFAOYSA-N 0.000 description 1
- BXCRLBBIZJSWNS-UHFFFAOYSA-N 2-hydroxyethyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCCO BXCRLBBIZJSWNS-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- DDGPBVIAYDDWDH-UHFFFAOYSA-N 3-[dodecyl(dimethyl)azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound CCCCCCCCCCCC[N+](C)(C)CC(O)CS([O-])(=O)=O DDGPBVIAYDDWDH-UHFFFAOYSA-N 0.000 description 1
- FPVVYTCTZKCSOJ-UHFFFAOYSA-N Ethylene glycol distearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCCCCCCCC FPVVYTCTZKCSOJ-UHFFFAOYSA-N 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NCHJGQKLPRTMAO-XWVZOOPGSA-N [(2R)-2-[(2R,3R,4S)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NCHJGQKLPRTMAO-XWVZOOPGSA-N 0.000 description 1
- QYIXCDOBOSTCEI-UHFFFAOYSA-N alpha-cholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 QYIXCDOBOSTCEI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- MRUAUOIMASANKQ-UHFFFAOYSA-O carboxymethyl-[3-(dodecanoylamino)propyl]-dimethylazanium Chemical compound CCCCCCCCCCCC(=O)NCCC[N+](C)(C)CC(O)=O MRUAUOIMASANKQ-UHFFFAOYSA-O 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- MRUAUOIMASANKQ-UHFFFAOYSA-N cocamidopropyl betaine Chemical compound CCCCCCCCCCCC(=O)NCCC[N+](C)(C)CC([O-])=O MRUAUOIMASANKQ-UHFFFAOYSA-N 0.000 description 1
- 229940073507 cocamidopropyl betaine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- HIEFXWXCLCHBPG-UHFFFAOYSA-L dipotassium;diiodide Chemical compound [K+].[K+].[I-].[I-] HIEFXWXCLCHBPG-UHFFFAOYSA-L 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229940100608 glycol distearate Drugs 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XSEOYPMPHHCUBN-FGYWBSQSSA-N hydroxylated lecithin Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCC[C@@H](O)[C@H](O)CCCCCCCC XSEOYPMPHHCUBN-FGYWBSQSSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940075468 lauramidopropyl betaine Drugs 0.000 description 1
- 229940094506 lauryl betaine Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- DVEKCXOJTLDBFE-UHFFFAOYSA-N n-dodecyl-n,n-dimethylglycinate Chemical compound CCCCCCCCCCCC[N+](C)(C)CC([O-])=O DVEKCXOJTLDBFE-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- GOJYXPWOUJYXJC-UHFFFAOYSA-M sodium;2-[1-(2-hydroxyethyl)-2-undecyl-4,5-dihydroimidazol-1-ium-1-yl]acetate;hydroxide Chemical compound [OH-].[Na+].CCCCCCCCCCCC1=NCC[N+]1(CCO)CC([O-])=O GOJYXPWOUJYXJC-UHFFFAOYSA-M 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- HVUCRESARJLKJG-UHFFFAOYSA-K trisodium 1-hexadecoxyhexadecane phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O.CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC HVUCRESARJLKJG-UHFFFAOYSA-K 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Abstract
Description
本発明は、水溶液中、ヨウ素系殺菌成分の析出が抑制された水性外用組成物に関する。また本発明は当該水性外用組成物が吐出部を備える容器に充填されてなる液体製剤に関する。 The present invention relates to an aqueous external composition in which precipitation of iodine-based sterilizing components is suppressed in an aqueous solution. Moreover, this invention relates to the liquid formulation with which the said aqueous | water-based external composition is filled with the container provided with a discharge part.
ヨウ素系殺菌成分は、殺菌効果、抗ウイルス活性等を有することが知られているが、ヨウ素は水溶性が低いことから適当な製剤化を行わなければ、使用することができなかった。従来、ヨウ素を可溶化する方法としては、ノニオン界面活性剤等を用いる方法が知られているが、長期保存時の安定性等で必ずしも満足のいくものではなかった。また、第四級アンモニウム塩及び両性界面活性剤を用いることで、ヨウ素を可溶化する方法が提案されている（特許文献１）。しかし、第四級アンモニウム塩の種類が限られ、かつ対イオンＩ−とヨウ素からなるコンプレックスを作るために、第四級アンモニウム塩を非常に多く配合する必要があり、それに応じて両性界面活性剤の配合量も多くなることから、当該組成物を哺乳類、特にヒトに対して適用することは困難であった。
また、口腔及び咽喉頭用の殺菌や消毒のために用いられる製剤として、一般的に「複方ヨード・グリセリン」が知られている（非特許文献１）。「複方ヨード・グリセリン」には、ヨウ素１．２重量％が配合されるとともに、当該ヨウ素を可溶化するためのヨウ化カリウムが２．４重量％も配合されている（ヨウ化カリウムは、水溶液中では電離してヨウ化物イオンとカリウムイオンになり、ヨウ化物イオンとヨウ素がコンプレックスを形成することでヨウ素を可溶化できる）。「複方ヨード・グリセリン」は古くから使用されており、一定の安全性が確保されているものの、一方で、ヨウ素には長期連用によるヨウ素中毒などが知られていることから、必要以上のヨウ化カリウムを配合しないことが望ましく、ヨウ素の新たな可溶化方法が求められていた。
Iodine-based bactericidal components are known to have bactericidal effects, antiviral activity, and the like, but iodine cannot be used unless it is properly formulated because of its low water solubility. Conventionally, as a method for solubilizing iodine, a method using a nonionic surfactant or the like is known, but it is not always satisfactory in terms of stability during long-term storage. In addition, a method for solubilizing iodine by using a quaternary ammonium salt and an amphoteric surfactant has been proposed (Patent Document 1). However, the type of quaternary ammonium salt is limited, and the counter ion I - to make complex consisting of iodine, it is necessary to blend so many quaternary ammonium salts, amphoteric surfactants accordingly Therefore, it has been difficult to apply the composition to mammals, particularly humans.
In addition, “compound iodine glycerin” is generally known as a preparation used for sterilization and disinfection for oral cavity and throat (Non-patent Document 1). “Compound iodine glycerin” contains 1.2% by weight of iodine and 2.4% by weight of potassium iodide for solubilizing the iodine (potassium iodide is an aqueous solution). Inside, it is ionized into iodide ions and potassium ions, and the iodide ions and iodine form a complex to solubilize iodine). “Composite iodine glycerin” has been used for a long time and has a certain level of safety. On the other hand, iodine is known to be iodine poisoning due to long-term continuous use. It is desirable not to add potassium, and a new method for solubilizing iodine has been demanded.
本発明の目的は、ヨウ素の析出が抑制された水性外用組成物を提供することである。特に本発明は、ヨウ化カリウムの配合量を少なくした場合でもヨウ素の析出が抑制されてなる水性外用組成物を提供することを目的とする。また、本発明は、当該水性外用組成物が吐出部を備える容器に充填されてなる液体製剤を提供することを目的とする。 An object of the present invention is to provide an aqueous external composition in which precipitation of iodine is suppressed. In particular, an object of the present invention is to provide an aqueous external composition in which precipitation of iodine is suppressed even when the blending amount of potassium iodide is reduced. Moreover, an object of this invention is to provide the liquid formulation with which the said aqueous | water-based external composition is filled with the container provided with a discharge part.
本発明者は、上記課題を解決すべき鋭意検討を重ねていたところ、ヨウ素に特定量のヨウ化カリウムと双性イオン化合物を配合することで、水性外用組成物中のヨウ素の析出を抑制できることを見出した。また、このようにヨウ素の析出が抑制されることで、本発明の水性外用組成物は、吐出部を備える容器に充填して液体製剤として調製することができ、このようにしてもヨウ素の析出により吐出部から液剤が射出しないという問題の発生を予防乃至回避することが可能になる。本発明はかかる知見に基づいて完成したものであり、下記の実施形態を有するものである。 The present inventor has conducted extensive studies to solve the above-mentioned problems, and by mixing a specific amount of potassium iodide and a zwitterionic compound with iodine, it is possible to suppress precipitation of iodine in the aqueous external composition. I found. In addition, since the precipitation of iodine is suppressed in this way, the aqueous external composition of the present invention can be prepared as a liquid preparation by filling a container having a discharge part. Therefore, it is possible to prevent or avoid the problem that the liquid agent is not injected from the discharge portion. The present invention has been completed based on this finding, and has the following embodiments.
（１）水性外用組成物
（1-1）ヨウ素系殺菌成分、ヨウ化カリウム及び双性イオン化合物を含有する水性外用組成物であって、ヨウ素系殺菌成分に含有されるヨウ素１モルに対してヨウ化カリウムが１〜４モルであり、かつ組成物中の双性イオン化合物が０．０１〜１０ｗ／ｖ％である水性外用組成物。
（1-2）ヨウ素系殺菌成分がヨウ素、ポビドンヨード、ノノキシノールヨード及びフェノキシヨードからなる群から選択される１種である（1-1）記載の水性外用組成物。
（1-3）双性イオン化合物がベタイン型界面活性剤、トリメチルグリシン及びリン脂質からなる群から選択される１種である（1-1）又は（1-2）記載の水性外用組成物。
（1-4）口腔及び咽喉頭粘膜適用のための（1-1）〜(1-3)のいずれかに記載の水性外用組成物。
（1-5）ヨウ素系殺菌成分、ヨウ化カリウム及び双性イオン化合物を含有する水性外用組成物であって、組成物中のヨウ素が０．０１〜１．５ｗ／ｖ％、ヨウ化カリウムが０．００６〜２ｗ／ｖ％、双性イオン化合物が０．０１〜１０ｗ／ｖ％である水性外用組成物。
(1) Aqueous composition for external use (1-1) An aqueous composition for external use containing an iodine sterilizing component, potassium iodide and a zwitterionic compound, with respect to 1 mole of iodine contained in the iodine sterilizing component The aqueous | water-based external composition whose potassium iodide is 1-4 mol and whose zwitterionic compound in a composition is 0.01-10 w / v%.
(1-2) The aqueous external composition according to (1-1), wherein the iodine-based bactericidal component is one selected from the group consisting of iodine, povidone iodine, nonoxynol iodine and phenoxy iodine.
(1-3) The aqueous external composition according to (1-1) or (1-2), wherein the zwitterionic compound is one selected from the group consisting of betaine surfactants, trimethylglycine and phospholipids.
(1-4) The aqueous external composition according to any one of (1-1) to (1-3) for application to the oral cavity and pharyngeal laryngeal mucosa.
(1-5) An aqueous external composition containing an iodine-based bactericidal component, potassium iodide and a zwitterionic compound, wherein iodine in the composition is 0.01 to 1.5 w / v%, potassium iodide is An aqueous external composition having 0.006 to 2 w / v% and a zwitterionic compound content of 0.01 to 10 w / v%.
（２）液体製剤
（2-1）（1-1）〜（1-5）のいずれかに記載の水性外用組成物が吐出部を備える容器に収容されてなる液体製剤であって、吐出部から水性外用組成物を患者の口腔内又は咽喉頭部へ射出させて使用される液体製剤。
(2) Liquid preparation (2-1 ) A liquid preparation in which the aqueous external composition according to any one of (1-1) to (1-5) is contained in a container having a discharge part, the discharge part A liquid preparation used by injecting an aqueous external composition into the oral cavity or throat of a patient.
（３）ヨウ素の析出抑制方法
（3-1）ヨウ素系殺菌成分を含有する水性外用組成物におけるヨウ素の析出抑制方法であって、ヨウ素系殺菌成分に含有されるヨウ素１モルあたりヨウ化カリウム１〜４モルを含む組成物に、双性イオン化合物を０．０１〜１０ｗ／ｖ％の割合で溶解させることを特徴とする方法。
（3-2）ヨウ素系殺菌成分がヨウ素、ポビドンヨード、ノノキシノールヨード及びフェノキシヨードからなる群から選択される１種である（3-1）記載の方法。
（3-3）双性イオン化合物がベタイン型界面活性剤、トリメチルグリシン及びリン脂質からなる群から選択される１種である（3-1）又は（3-2）記載の方法。
（3-4）ヨウ素系殺菌成分を含有する水性外用組成物におけるヨウ素の析出抑制方法であって、ヨウ素０．０１〜１．５ｗ／ｖ％及びヨウ化カリウム０．００６〜２ｗ／ｖ％を含む組成物に、双性イオン化合物を０．０１〜１０ｗ／ｖ％の割合で溶解させることを特徴とする方法。
(3) Iodine precipitation suppression method (3-1) A method for suppressing iodine precipitation in an aqueous external composition containing an iodine-based sterilizing component, wherein 1 potassium iodide per mole of iodine contained in the iodine-based sterilizing component A method comprising dissolving a zwitterionic compound at a ratio of 0.01 to 10 w / v% in a composition containing ˜4 mol.
(3-2) The method according to (3-1), wherein the iodine-based bactericidal component is one selected from the group consisting of iodine, povidone iodine, nonoxynol iodine, and phenoxy iodide.
(3-3) The method according to (3-1) or (3-2), wherein the zwitterionic compound is one selected from the group consisting of betaine surfactants, trimethylglycine and phospholipids.
(3-4) A method for suppressing precipitation of iodine in an aqueous external composition containing an iodine-based sterilizing component, comprising 0.01 to 1.5 w / v% iodine and 0.006 to 2 w / v% potassium iodide A method comprising dissolving a zwitterionic compound in a composition containing 0.01 to 10 w / v%.
ヨウ素は水に溶解しにくく、また、ヨウ化物イオンとのコンプレックスは比較的不安定であることから、ヨウ化カリウムの含有量が少ない場合には、水を溶媒として含有する水性外用組成物中でヨウ素が析出しやすいものの、本発明の水性外用組成物によれば、ヨウ化カリウムの配合量を従来よりも少なくしても、ヨウ素の析出を有意に抑制することができる。 Iodine is difficult to dissolve in water, and the complex with iodide ions is relatively unstable. Therefore, when the content of potassium iodide is low, the composition is used in an aqueous external composition containing water as a solvent. Although iodine easily precipitates, according to the aqueous external composition of the present invention, iodine precipitation can be significantly suppressed even if the amount of potassium iodide is less than the conventional amount.
このように本発明の水性外用組成物は、ヨウ素の析出が抑制されているため、吐出部を備える容器に充填して液体製剤として調製することができ、このようにしてもヨウ素の析出により吐出部から液剤が射出しないという問題の発生を予防乃至回避することができる。 Thus, since the aqueous | water-based external composition of this invention has suppressed precipitation of iodine, it can fill a container provided with a discharge part and can prepare it as a liquid formulation, and also discharges by precipitation of iodine in this way. Occurrence of the problem that the liquid agent does not inject from the part can be prevented or avoided.
（１）水性外用組成物
本発明の水性外用組成物は、溶媒として水を含む外用組成物であり、当該外用組成物中に（Ａ）ヨウ素系殺菌成分、（Ｂ）ヨウ化カリウム及び（Ｃ）双性イオン化合物が特定のモル比又は濃度で溶解してなる溶液状の組成物である。
以下、各成分について説明する。
(1) Aqueous External Composition The aqueous external composition of the present invention is an external composition containing water as a solvent. In the external composition, (A) iodine-based bactericidal component, (B) potassium iodide and (C ) A solution-like composition in which a zwitterionic compound is dissolved at a specific molar ratio or concentration.
Hereinafter, each component will be described.
（Ａ）ヨウ素系殺菌成分
ヨウ素系殺菌成分としては、ヨウ素（分子量：２５３．８）を含む化合物であれば、特に制限されないが、例えば、ヨウ素、ポビドンヨード、ノノキシノールヨード及びフェノキシヨードからなる群から選択される１種が挙げられる。なかでも、殺菌効果及び製剤安定性の点から、好ましくは、ヨウ素及びポビドンヨードが挙げられる。なお、これらのヨウ素系殺菌成分は、１種単独で使用してもよいが、２種以上を任意に組み合わせて使用することもできる。
(A) Iodine-based bactericidal component The iodine-based bactericidal component is not particularly limited as long as it is a compound containing iodine (molecular weight: 253.8). For example, a group consisting of iodine, povidone iodine, nonoxynol iodine, and phenoxy iodo 1 type selected from is mentioned. Among these, iodine and povidone iodine are preferable from the viewpoint of bactericidal effect and formulation stability. In addition, although these iodine type bactericidal components may be used individually by 1 type, they can also be used in combination of 2 or more types arbitrarily.
本発明の水性外用組成物における当該ヨウ素系殺菌成分の配合割合は、後述するヨウ化カリウム及び双性イオン化合物の配合量を考慮しながら適宜設定されるが、ヨウ素として、通常、０．０１〜１．５ｗ／ｖ％配合することができ、好ましくは、０．０３〜１ｗ／ｖ％、より好ましくは０．０５〜１ｗ／ｖ％、さらに好ましくは０．１〜１ｗ／ｖ％である。 The blending ratio of the iodine-based bactericidal component in the aqueous external composition of the present invention is appropriately set in consideration of the blending amounts of potassium iodide and zwitterionic compound described later. 1.5 w / v% can be blended, preferably 0.03 to 1 w / v%, more preferably 0.05 to 1 w / v%, still more preferably 0.1 to 1 w / v%.
（Ｂ）ヨウ化カリウム
ヨウ化カリウム（分子量：１６６．０）は、従来、水に溶けにくいヨウ素を可溶化する目的で使用されている。ヨウ化カリウムは、水溶液中で電離してヨウ化物イオンとカリウムイオンになり、当該ヨウ化物イオンがヨウ素とコンプレックスを形成し、三ヨウ化物イオンとなることでヨウ素を溶解させることができる。
(B) Potassium iodide Potassium iodide (molecular weight: 166.0) has been conventionally used for the purpose of solubilizing iodine that is hardly soluble in water. Potassium iodide is ionized in an aqueous solution to form iodide ions and potassium ions, and the iodide ions form a complex with iodine to form triiodide ions, whereby iodine can be dissolved.
本発明の水性外用組成物における当該ヨウ化カリウムの配合割合は、ヨウ素１モルあたり１〜４モルであり、好ましくは１〜３モル、より好ましくは１〜２モルである。例えば、ヨウ素系殺菌成分としてヨウ素を採用する場合、ヨウ素１重量部あたり、ヨウ化カリウムは、０．６６〜２．６４重量部であり、好ましくは０．６６〜１．９８重量部であり、より好ましくは０．６６〜１．３２重量部である。また、当該ヨウ化カリウムの配合割合は、ヨウ素の可溶化及び安全性の観点から０．００６〜２ｗ／ｖ％が好ましい。このように、ヨウ化カリウムの配合量が従来よりも少なくても、後述する双性イオン化合物を配合することで、ヨウ素の析出を効果的に抑制することが可能となる。 The compounding ratio of the potassium iodide in the aqueous external composition of the present invention is 1 to 4 mol, preferably 1 to 3 mol, more preferably 1 to 2 mol per mol of iodine. For example, when iodine is employed as the iodine-based sterilizing component, potassium iodide is 0.66 to 2.64 parts by weight, preferably 0.66 to 1.98 parts by weight, per 1 part by weight of iodine. More preferably, it is 0.66-1.32 weight part. Moreover, the blending ratio of the potassium iodide is preferably 0.006 to 2 w / v% from the viewpoint of iodine solubilization and safety. Thus, even if the compounding quantity of potassium iodide is less than before, it becomes possible to suppress precipitation of iodine effectively by compounding the zwitterionic compound described later.
（Ｃ）双性イオン化合物
本発明の水性外用組成物には、上記成分（Ａ）及び（Ｂ）に加えて、双性イオン化合物が配合される。
(C) Zwitterionic compound In addition to the components (A) and (B), a zwitterionic compound is added to the aqueous external composition of the present invention.
双性イオン化合物は、分子内にカチオン中心とアニオン中心を持つ化合物であり、医薬品、医薬部外品、及び化粧品などの人体に適用される製品に通常使用されるものであれば特に限定されず、例えば、ラウリルベタイン（ラウリルジメチルアミノ酢酸ベタイン）等のＮ−アルキル−Ｎ，Ｎ−ジメチルアミノ酸ベタイン；コカミドプロピルベタイン、ラウラミドプロピルベタイン等の脂肪酸アミドアルキル−Ｎ，Ｎ−ジメチルアミノ酸ベタイン；ココアンホ酢酸ナトリウム、ラウロアンホ酢酸ナトリウム等のイミダゾリン型ベタイン；アルキルジメチルタウリン等のアルキルスルホベタイン；ラウリルヒドロキシスルホベタイン等のアルキルヒドロキシスルホベタイン；アルキルジメチルアミノエタノール硫酸エステル等の硫酸型ベタイン；アルキルジメチルアミノエタノールリン酸エステル等のリン酸型ベタイン；ポリメタクリロイルエチルジメチルベタイン、Ｎ−メタクリロイルオキシエチルＮ，Ｎ−ジメチルアンモニウム−α−メチルカルボキシベタイン・メタクリル酸アルキル共重合体等のメタクリル酸誘導体；ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルセリン、スフィンゴミエリン等のスフィンゴリン脂質、レシチン、リゾレシチン、大豆リン脂質、水素添加大豆リン脂質、部分水素添加大豆リン脂質、卵黄リン脂質、水素添加卵黄リン脂質、部分水素添加卵黄リン脂質、水酸化レシチン等のリン脂質類（分子内にリン脂質もしくはその類似構造を含む化合物であれば、特に制限はない）；トリメチルグリシン；両性化デンプン；シリコーン系両性界面活性剤等が挙げられる。なかでも、外用組成物、特に口腔内において使用する場合、その製剤安定性及び味を考慮し、好ましくは、ベタイン型界面活性剤、トリメチルグリシン、リン脂質等が挙げられる。なお、これらの双性イオン化合物は、１種単独で使用してもよいが、２種以上を任意に組み合わせて使用することもできる。 A zwitterionic compound is a compound having a cation center and an anion center in the molecule, and is not particularly limited as long as it is usually used in products applied to the human body such as pharmaceuticals, quasi drugs, and cosmetics. N-alkyl-N, N-dimethylamino acid betaines such as lauryl betaine (lauryldimethylaminoacetic acid betaine); fatty acid amide alkyl-N, N-dimethylamino acid betaines such as cocamidopropyl betaine and lauramidopropyl betaine; Imidazoline-type betaines such as sodium acetate and sodium lauroamphoacetate; alkylsulfobetaines such as alkyldimethyltaurine; alkylhydroxysulfobetaines such as laurylhydroxysulfobetaine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate; Phosphoric acid-type betaines such as alkyldimethylaminoethanol phosphate; Methacrylic acid derivatives such as polymethacryloylethyldimethylbetaine, N-methacryloyloxyethyl N, N-dimethylammonium-α-methylcarboxybetaine / alkyl methacrylate copolymer; Sphingophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, lecithin, lysolecithin, soybean phospholipid, hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, egg yolk phospholipid, hydrogenated egg yolk phospholipid, partial hydrogen Phospholipids such as added egg yolk phospholipid and hydroxylated lecithin (no particular limitation as long as it is a compound containing a phospholipid or a similar structure in its molecule); trimethylglycine; amphoteric starch; Amphoteric surfactants and the like. Among them, when used in an external composition, particularly in the oral cavity, betaine surfactants, trimethylglycine, phospholipids and the like are preferably used in consideration of the formulation stability and taste. In addition, although these zwitterionic compounds may be used individually by 1 type, they can also be used in combination of 2 or more types arbitrarily.
本発明の水性外用組成物における当該双性イオン化合物の配合割合は、組成物中０．０１〜１０ｗ／ｖ％であり、好ましくは０．０５〜１０ｗ／ｖ％であり、より好ましくは０．１〜８ｗ／ｖ％であり、さらに好ましくは０．５〜５ｗ／ｖ％であり、とくに好ましくは１〜５ｗ／ｖ％である。この範囲内であれば、ヨウ化カリウムの配合量が従来より少なくても、ヨウ素の析出を効果的に抑制することが可能となる。 The mixing ratio of the zwitterionic compound in the aqueous external composition of the present invention is 0.01 to 10 w / v% in the composition, preferably 0.05 to 10 w / v%, more preferably 0.8. It is 1-8 w / v%, More preferably, it is 0.5-5 w / v%, Most preferably, it is 1-5 w / v%. Within this range, it is possible to effectively suppress the precipitation of iodine even if the amount of potassium iodide is less than the conventional amount.
（Ｄ）水性外用組成物に配合するその他の成分
本発明の水性外用組成物は、上記成分〔（Ａ）＋（Ｂ）＋（Ｃ）〕に加えて、さらにこれらの成分を溶解するための溶媒を含む。かかる溶媒として、少なくとも水を挙げることができる。
(D) Other components to be blended in aqueous external composition In addition to the above components [(A) + (B) + (C)], the aqueous external composition of the present invention further dissolves these components. Contains solvent. An example of such a solvent is water.
水は特に制限されない。例えば、精製水、蒸留水、イオン交換水、超純水、滅菌水などを、制限なく使用することができる。好ましくは精製水である。本発明の水性外用組成物における当該水の配合割合はヨウ素系殺菌成分、ヨウ化カリウム及び双性イオン化合物を溶解できる量であればよく、通常、１ｗ／ｖ％以上であり、好ましくは、５〜９９ｗ／ｖ％の範囲から適宜設定することができる。好ましくは、好ましくは１０〜９５ｗ／ｖ％である。 Water is not particularly limited. For example, purified water, distilled water, ion exchange water, ultrapure water, sterilized water, and the like can be used without limitation. Preferably it is purified water. The mixing ratio of the water in the aqueous external composition of the present invention may be any amount that can dissolve the iodine-based bactericidal component, potassium iodide, and zwitterionic compound, and is usually 1 w / v% or more, preferably 5 It can set suitably from the range of -99w / v%. Preferably, it is preferably 10 to 95 w / v%.
上記成分が溶解する限り、溶媒には、水と相溶性のある他の溶剤が含まれていてもよい。かかる溶剤として、好ましくはエタノール、グリセリン、プロピレングリコール、ジプロピレングリコールなどを挙げることができる。その溶媒全体に占める割合は、例えばエタノールの場合、通常６０容量％以下、好ましくは、５０容量％以下、より好ましくは３０容量％以下、更に好ましくは２５容量％以下、特に好ましくは０〜２０容量％程度である。 As long as the said component melt | dissolves, the solvent may contain the other solvent compatible with water. Preferred examples of such a solvent include ethanol, glycerin, propylene glycol, dipropylene glycol and the like. For example, in the case of ethanol, the proportion of the total solvent is usually 60% by volume or less, preferably 50% by volume or less, more preferably 30% by volume or less, still more preferably 25% by volume or less, particularly preferably 0 to 20% by volume. %.
（Ｅ）任意成分
本発明の水性外用組成物には、本発明の効果を損なわない範囲であれば、他の成分を適宜選択し配合することができる。例えば、追加の薬効成分、双性イオン化合物以外の界面活性剤並びに医薬製剤の調製に一般的に使用される希釈剤、ｐＨ調整剤（緩衝剤）、粘度調整剤、安定化剤、防腐剤、矯味剤（甘味料を含む）、矯臭剤（香料を含む）、着色料等の各種添加剤を挙げることができる。
(E) Optional component In the aqueous external composition of the present invention, other components can be appropriately selected and blended as long as the effects of the present invention are not impaired. For example, additional medicinal ingredients, surfactants other than zwitterionic compounds, diluents commonly used in the preparation of pharmaceutical formulations, pH adjusters (buffering agents), viscosity adjusters, stabilizers, preservatives, Various additives such as a corrigent (including a sweetener), a corrigent (including a fragrance), and a colorant can be exemplified.
追加の薬効成分としては、ヨウ素系殺菌成分の作用効果（殺菌効果、抗ウイルス活性等）を損なわないものを挙げることができ、例えば気管支拡張薬、鎮咳薬、去痰薬、消炎薬、解熱鎮痛薬、抗ヒスタミン薬、殺菌剤、胃粘膜保護薬、カフェイン類、ビタミン薬、漢方薬、生薬成分を挙げることができる。 Examples of additional medicinal ingredients include those that do not impair the action effects (bactericidal effects, antiviral activity, etc.) of iodine-based bactericidal ingredients. , Antihistamines, bactericides, gastric mucosa protective agents, caffeine, vitamins, herbal medicines, herbal medicines.
双性イオン化合物以外の界面活性剤としては、ノニオン界面活性剤、カチオン界面活性剤、アニオン界面活性剤等が挙げられる（両性界面活性剤は双性イオン化合物に含まれる）が、水性外用組成物の熱安定性及び流動性の観点から、ノニオン性の親水性界面活性剤が好ましい。ノニオン性の親水性界面活性剤としては、ポリオキシエチレン（以下、「ＰＯＥ」と略称する場合がある）付加タイプの界面活性剤が好適であり、例えば、ＰＯＥ（１０〜５０モル）フィトステロールエーテル、ＰＯＥ（１０〜５０モル）ジヒドロコレステロールエーテル、ＰＯＥ（１０〜５０モル）２−オクチルドデシルエーテル、ＰＯＥ（１０〜５０モル）デシルテトラデシルエーテル、ＰＯＥ（１０〜５０モル）オレイルエーテル、ＰＯＥ（１０〜５０モル）セチルエーテル、ＰＯＥ（５〜３０モル）ポリオキシプロピレン（５〜３０モル）２−デシルテトラデシルエーテル、ＰＯＥ（１０〜５０モル）ポリオキシプロピレン（２〜３０モル）セチルエーテルなどのポリオキシアルキレンアルキルエーテル、ＰＯＥ（３〜２００モル）ポリオキシプロピレン（１５〜７０モル）グリコールなどのポリオキシエチレンポリオキシプロピレングリコール；これらのリン酸・リン酸塩（ＰＯＥセチルエーテルリン酸ナトリウムなど）；ＰＯＥ硬化ヒマシ油；ＰＯＥ（２０〜６０モル）ソルビタンモノオレート、ＰＯＥ（１０〜６０モル）ソルビタンモノイソステアレート、ＰＯＥ（１０〜８０モル）グリセリルモノイソステアレート、ＰＯＥ（１０〜３０モル）グリセリルモノステアレート、ＰＯＥ（２０〜１００）ポリオキシプロピレン変性シリコーン、ＰＯＥ・アルキル変性シリコーン、モノラウリン酸ポリエチレングリコール、モノパルミチン酸ポリエチレングリコール、モノステアリン酸ポリエチレングリコール、ジラウリン酸ポリエチレングリコール、ジパルミチン酸ポリエチレングリコール、ジステアリン酸ポリエチレングリコール、ジオレイン酸ポリエチレングリコール、ジリシノレイン酸ポリエチレングリコールなどなどから選択される１種以上を使用することができる。 Examples of surfactants other than zwitterionic compounds include nonionic surfactants, cationic surfactants, anionic surfactants and the like (amphoteric surfactants are included in zwitterionic compounds). From the viewpoint of thermal stability and fluidity, a nonionic hydrophilic surfactant is preferred. As the nonionic hydrophilic surfactant, a polyoxyethylene (hereinafter sometimes abbreviated as “POE”) addition type surfactant is suitable. For example, POE (10 to 50 mol) phytosterol ether, POE (10-50 mol) dihydrocholesterol ether, POE (10-50 mol) 2-octyldodecyl ether, POE (10-50 mol) decyltetradecyl ether, POE (10-50 mol) oleyl ether, POE (10-10 mol) 50 mol) cetyl ether, POE (5-30 mol) polyoxypropylene (5-30 mol) 2-decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether, etc. Oxyalkylene alkyl ether, POE (3-200 mol) Polyoxyethylene polyoxypropylene glycol such as reoxypropylene (15 to 70 mol) glycol; Phosphoric acid / phosphate (such as POE cetyl ether sodium phosphate); POE hydrogenated castor oil; POE (20 to 60 mol) Sorbitan monooleate, POE (10-60 mol) sorbitan monoisostearate, POE (10-80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl monostearate, POE (20-100) polyoxy Propylene-modified silicone, POE / alkyl-modified silicone, polyethylene glycol monolaurate, polyethylene glycol monopalmitate, polyethylene glycol monostearate, polyethylene glycol dilaurate, polyethylene glycol dipalmitate Ethylene glycol, polyethylene glycol distearate, polyethylene glycol dioleate, may be used one or more selected from etc. Jirishinorein acid polyethylene glycol.
（Ｆ）水性外用組成物の調製方法及び使用方法
本発明の水性外用組成物は、上記成分（Ａ）、（Ｂ）及び（Ｄ）を混合、溶解し、そこに成分（Ｄ）に溶解した成分（Ｃ）を加え、混合、溶解することで調製することができる。ここで、必要に応じて、グリセリン、プロピレングリコールなどを混合してもよい。
(F) Preparation method and use method of aqueous external composition The aqueous external composition of the present invention was prepared by mixing and dissolving the components (A), (B) and (D), and dissolving them in the component (D). It can be prepared by adding component (C), mixing and dissolving. Here, glycerin, propylene glycol and the like may be mixed as necessary.
本発明の水性外用組成物は、溶媒として少なくとも水を含み、当該溶媒中に（Ａ）ヨウ素系殺菌成分、（Ｂ）ヨウ化カリウム及び（Ｃ）双性イオン化合物が溶解してなる液状の組成物であって、外用液剤（例えば、口腔用液剤、特に口腔粘膜や咽喉頭粘膜適用液剤）として、殺菌、消毒等の目的に好ましく使用することができる。 The aqueous composition for external use of the present invention contains at least water as a solvent, and a liquid composition in which (A) iodine-based bactericidal component, (B) potassium iodide and (C) a zwitterionic compound are dissolved in the solvent. It can be preferably used as a liquid for external use (for example, liquid for oral cavity, particularly liquid for oral mucosa and throat laryngeal mucosa) for the purpose of sterilization and disinfection.
上記の用途で、本発明の水性外用組成物は、通常、１日１回〜複数回、適時、塗布やうがい等をすることにより使用される。なお、うがいの場合は、水性外用組成物を水等で適宜希釈して使用することもできる。 In the above applications, the aqueous external composition of the present invention is usually used by applying, gargleing, etc. once a day to several times in a timely manner. In the case of gargle, the aqueous external composition can be appropriately diluted with water or the like.
（２）液体製剤
本発明の液体製剤は、前述する本発明の水性外用組成物が、吐出部を備える容器に収容されてなるものである。当該液体製剤は、上記容器の吐出部から水性外用組成物を患者の口腔内又は咽喉頭部に射出させて使用することができる。ここで患者とは、皮膚や口腔内、咽喉頭部の殺菌、消毒を所望する者であり、本発明の水性外用組成物により当該目的の達成が期待されるヒトを含む哺乳類、好ましくはヒトを意味する。
(2) Liquid preparation The liquid preparation of the present invention is one in which the aqueous external composition of the present invention described above is contained in a container having a discharge part. The liquid preparation can be used by ejecting the aqueous external composition from the discharge part of the container into the oral cavity or throat of the patient. Here, the patient is a person who desires sterilization and disinfection of the skin, oral cavity, and pharyngeal head, and mammals including humans, preferably humans, who are expected to achieve the object by the aqueous external composition of the present invention. means.
本発明が対象とする吐出部を備える容器（以下、これを「吐出装置」と称する）は、特に制限されず、例えばトリガータイプの吐出装置、及びプッシュポンプタイプの吐出装置のいずれもが含まれる。具体的には、特開２００１−１７１７６４号公報、特開２００２−３６２６０５号公報、特開２００４−８３４号公報、特開２００４−３５９２４２号公報、特開２００４−３５９２４１号公報、特開２００４−３５９２３８号公報、特開２００４−３５２３４３号公報、特開２００４−３５２３３３号公報、特開２００７−２７７１２５号公報、及び特開２０１４−１４１２８８号公報などに記載されている吐出装置をいずれも使用することができる。なかでも好ましくは特開２０１４−１４１２８８号公報に記載されている吐出装置である。特開２０１４−１４１２８８号公報に記載されている吐出装置は、販売名「のどぬーるスプレーＢ」（小林製薬株式会社製）等において使用される吐出装置であり、このように、吐出部がノズル形状になっている吐出装置を用いれば、患部が喉など塗布しにくい場合でも液剤を容易に塗布することが可能となる。当該ノズルの長さは、好ましくは１〜８ｃｍ程度、より好ましくは２〜７ｃｍ程度であり、またノズルの吐出口は直径が０．２〜１．５ｍｍ程度である。本発明の水性外用組成物であれば、ヨウ素の析出が抑えられていることから、このようにノズルが長く、また吐出口の径が小さい場合であっても詰まることが抑制され、液剤が射出できないという問題の発生を予防乃至回避することができる。 The container provided with the discharge section targeted by the present invention (hereinafter referred to as “discharge device”) is not particularly limited, and includes, for example, both a trigger type discharge device and a push pump type discharge device. . Specifically, JP-A Nos. 2001-171664, 2002-362605, 2004-8334, 2004-359242, 2004-359241, 2004-359238. No. 2004, No. 2004-352343, No. 2004-352333, No. 2007-277125, and No. 2014-141288 may be used. it can. Of these, the discharge device described in JP-A No. 2014-141288 is preferable. The discharge device described in Japanese Patent Application Laid-Open No. 2014-141288 is a discharge device used under the trade name “Nodou-Ru Spray B” (manufactured by Kobayashi Pharmaceutical Co., Ltd.) and the like. If a discharge device having a nozzle shape is used, the liquid agent can be easily applied even when the affected area is difficult to apply such as the throat. The length of the nozzle is preferably about 1 to 8 cm, more preferably about 2 to 7 cm, and the nozzle outlet has a diameter of about 0.2 to 1.5 mm. In the case of the aqueous external composition of the present invention, since precipitation of iodine is suppressed, clogging is suppressed even when the nozzle is long and the diameter of the discharge port is small, and the liquid agent is injected. It is possible to prevent or avoid the occurrence of the problem of being impossible.
一回の射出（ワンプッシュ）による吐出装置からの水性外用組成物の射出量は、制限されないものの、通常０．０３〜３ｍＬ程度である。好ましくは０．１〜２ｍＬ、より好ましくは０．３〜１．５ｍＬ、さらに好ましくは０．５〜１．０ｍＬである。 Although the injection amount of the aqueous external composition from the discharge device by one injection (one push) is not limited, it is usually about 0.03 to 3 mL. Preferably it is 0.1-2 mL, More preferably, it is 0.3-1.5 mL, More preferably, it is 0.5-1.0 mL.
（３）ヨウ素の析出抑制方法
本発明は、溶媒として水を含有する水性液体中における（Ａ）ヨウ素の析出抑制方法を提供する。当該方法は、当該水性液体の調製に際して、（Ａ）ヨウ素系殺菌成分に加えて、（Ｂ）ヨウ化カリウム及び（Ｃ）双性イオン化合物を配合することで実施することができる。
(3) Method for inhibiting precipitation of iodine The present invention provides (A) a method for inhibiting the precipitation of iodine in an aqueous liquid containing water as a solvent. In the preparation of the aqueous liquid, the method can be carried out by blending (B) potassium iodide and (C) a zwitterionic compound in addition to (A) iodine-based sterilizing component.
本発明の方法で使用する（Ａ）ヨウ素系殺菌成分、（Ｂ）ヨウ化カリウム、及び（Ｃ）双性イオン化合物、並びに（Ｄ）溶媒の種類、並びにその配合割合は、上記（１）で説明した通りである。従って、当該発明において、上記（１）における（Ａ）〜（Ｄ）の記載を援用することができる。 The types of (A) iodine-based bactericidal component, (B) potassium iodide, (C) zwitterionic compound, and (D) solvent used in the method of the present invention, and the blending ratio thereof are the above (1). As explained. Therefore, in the said invention, the description of (A)-(D) in said (1) can be used.
本発明の水性液体における（Ａ）ヨウ素の析出抑制方法において、対象とする水性液体の調製方法も上記（１）の（Ｆ）で説明した通りである。従って、当該発明において、上記（１）における（Ｆ）の記載を援用することができる。 In the method for suppressing precipitation of iodine (A) in the aqueous liquid of the present invention, the method for preparing the target aqueous liquid is also as described in (F) of (1) above. Therefore, in the said invention, the description of (F) in said (1) can be used.
析出を抑制する対象の水性液体には、本発明の効果を妨げない限り、上記（Ａ）〜（Ｃ）及び（Ｄ）、または（Ａ）〜（Ｄ）の他、任意成分として、医薬製剤の調製に一般的に使用される安定化剤、防腐剤、緩衝剤、ｐＨ調整剤等の各種添加剤を配合してもよい。かかる各成分の具体例については、上記（１）の（Ｅ）で説明した通りである。従って、当該発明において、上記（１）における（Ｅ）の記載を援用することができる。 In addition to the above (A) to (C) and (D), or (A) to (D), as an optional component, a pharmaceutical preparation may be used as an aqueous liquid to be controlled for precipitation unless the effects of the present invention are hindered. Various additives such as stabilizers, preservatives, buffers, pH adjusters and the like generally used in the preparation of the above may be blended. Specific examples of such components are as described in (E) of (1) above. Therefore, in the said invention, the description of (E) in said (1) can be used.
本発明の析出抑制方法によれば、後述する実験例に示すように、水性外用組成物中でのヨウ素の溶解安定性を向上することで、その析出を抑制し、ヨウ素を含む水性外用組成物の外観及びその品質を安定させることが可能になる。 According to the precipitation inhibiting method of the present invention, as shown in the experimental examples described later, by improving the dissolution stability of iodine in the aqueous external composition, the precipitation is suppressed, and the aqueous external composition containing iodine It is possible to stabilize the appearance and quality of the.
以下、実験例及び実施例に基づいて、本発明を具体的に説明する。但し、本発明はこれらによって何ら限定されるものではない。 Hereinafter, the present invention will be specifically described based on experimental examples and examples. However, the present invention is not limited by these.
実験例 ヨウ素の溶解安定性評価
水性外用組成物（実施例１〜２４、比較例１〜２及び参考例１）の調製
表１〜６に記載する処方に従って、水を溶媒とする液体組成物を調製した。具体的には、実施例１〜２０、比較例１及び参考例１では、まず精製水に双性イオン化合物を溶解し、そこへヨウ素、ヨウ化カリウム、エタノール（９５ｖｏｌ％）及び精製水を混合、溶解したものを加え、均一になるまで撹拌した。均一になったのを確認したら、精製水でメスアップして全体を１００ｍＬに調製した。実施例２１〜２４及び比較例２では、まずヨウ素、ヨウ化カリウム、エタノール（９５ｖｏｌ％）及び精製水を混合、溶解し、そこへ８０℃でプロピレングリコールに溶解又は分散させた双性イオン化合物を加え、均一になるまで撹拌した。均一になったのを確認したら、精製水でメスアップして全体を１００ｍＬに調製した。
Experimental example Dissolution stability evaluation of iodine
Preparation of aqueous external compositions (Examples 1 to 24, Comparative Examples 1 to 2 and Reference Example 1) According to the formulations described in Tables 1 to 6, liquid compositions using water as a solvent were prepared. Specifically, in Examples 1 to 20, Comparative Example 1 and Reference Example 1, a zwitterionic compound is first dissolved in purified water, and iodine, potassium iodide, ethanol (95 vol%) and purified water are mixed therewith. The dissolved material was added and stirred until uniform. When it was confirmed that it became uniform, the whole was adjusted to 100 mL with purified water. In Examples 21 to 24 and Comparative Example 2, first, iodine, potassium iodide, ethanol (95 vol%) and purified water were mixed and dissolved, and then a zwitterionic compound dissolved or dispersed in propylene glycol at 80 ° C. was mixed therewith. Add and stir until uniform. When it was confirmed that it became uniform, the whole was adjusted to 100 mL with purified water.
水性外用組成物中におけるヨウ素の溶解安定性評価（析出抑制評価）
上記で調製した水性外用組成物（実施例１〜２４、比較例１〜２及び参考例１）の全量を、それぞれバイアル瓶に入れ、２５℃条件で静置した。２０時間静置した後に目視（外観観察）で析出（析出物：ヨウ素）の有無を確認し、以下の基準に基づき、評価した。なお、比較例１におけるヨウ素の析出量を「×」とした。
（評価基準）
○：ヨウ素（光沢のある褐色結晶物）の析出なし
△：ヨウ素（光沢のある褐色結晶物）の析出が見られるが、僅かである
×：ヨウ素（光沢のある褐色結晶物）の析出が多く見られる（比較例１）
Evaluation of dissolution stability of iodine in aqueous composition for external use (deposition inhibition evaluation)
The total amount of the aqueous external composition prepared above (Examples 1 to 24, Comparative Examples 1 to 2 and Reference Example 1) was put in a vial and allowed to stand at 25 ° C. After standing for 20 hours, the presence or absence of precipitation (precipitate: iodine) was confirmed visually (appearance observation), and evaluated based on the following criteria. The amount of iodine deposited in Comparative Example 1 was “x”.
(Evaluation criteria)
○: No precipitation of iodine (glossy brown crystalline substance) Δ: Precipitation of iodine (shiny brown crystalline substance) is observed, but slight x: Many precipitations of iodine (shiny brown crystalline substance) Seen (Comparative Example 1)
結果
結果を表１〜６に示す。
The results are shown in Tables 1-6.
参考例１に示すように、ヨウ素１モルに対して、ヨウ化カリウムを５モル配合した場合には、双性イオン化合物を含有しなくてもヨウ素の析出を抑えることができたが、ヨウ素１モルに対してヨウ化カリウムを１モルとし、双性イオン化合物を含有しない比較例１及び２では、２５℃条件下での保存（２０時間）で、ヨウ素の析出が見られた。これに対して、双性イオン化合物を含有する実施例１〜２４では、ヨウ素の析出を顕著に抑制することができた。特に、１ｗ／ｖ％以上の割合で双性イオン化合物を配合することで、高い析出抑制効果を得ることができた（実施例３〜２４）。また、ヨウ化カリウムの含有量を、ヨウ素１モルに対して２モル、３モルとした場合でも、同様にヨウ素の析出を抑制できることが確認された。 As shown in Reference Example 1, when 5 mol of potassium iodide was added to 1 mol of iodine, precipitation of iodine could be suppressed without containing a zwitterionic compound. In Comparative Examples 1 and 2 in which 1 mol of potassium iodide was used with respect to 1 mol and no zwitterionic compound was contained, precipitation of iodine was observed during storage at 25 ° C. (20 hours). On the other hand, in Examples 1-24 containing a zwitterionic compound, precipitation of iodine could be remarkably suppressed. In particular, a high precipitation suppression effect could be obtained by blending the zwitterionic compound at a ratio of 1 w / v% or more (Examples 3 to 24). Moreover, it was confirmed that precipitation of iodine can be similarly suppressed even when the content of potassium iodide is 2 mol or 3 mol with respect to 1 mol of iodine.
また、実施例５の組成物を、販売名「のどぬーるスプレーＢ」（小林製薬株式会社製）の吐出装置（特開２０１４−１４１２８８号公報に記載の吐出装置）に充填し、１週間に亘り、毎日３プッシュして液体外用組成物を射出させたが、ノズル（長さ：約６ｃｍ、吐出口の直径：約０．８ｍｍ）の詰まりを抑制できており（ヨウ素の析出が認められず）、期間中、良好に射出することができた。 In addition, the composition of Example 5 was filled into a discharge device (a discharge device described in JP-A No. 2014-141288) under the trade name “Nodo Nuru Spray B” (manufactured by Kobayashi Pharmaceutical Co., Ltd.) for 1 week. The liquid composition for external application was injected 3 pushes every day, but clogging of the nozzle (length: about 6 cm, discharge port diameter: about 0.8 mm) was suppressed (precipitation of iodine was observed). Ii) during the period, the injection was good.
処方例１〜１５
表７及び８に示す処方にしたがって、水性外用組成物（処方例１〜１５）を調製した。これら水性外用組成物においても、双性イオン化合物を含有しない場合に比べてヨウ素の溶解安定性が向上し、析出が抑制できる傾向が認められた。
Formulation Examples 1-15
According to the formulations shown in Tables 7 and 8, aqueous external compositions (formulation examples 1 to 15) were prepared. Also in these aqueous external compositions, it was recognized that the dissolution stability of iodine was improved and precipitation could be suppressed as compared with the case where no zwitterionic compound was contained.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115517267A (en) * | 2022-10-17 | 2022-12-27 | 岳阳渔美康生物科技有限公司 | High-distribution-coefficient compound iodine solution for breeding and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02115105A (en) * | 1988-10-24 | 1990-04-27 | Kao Corp | Sterilizing and disinfecting agent composition |
| JP2003183169A (en) * | 2001-12-19 | 2003-07-03 | Toho Earthtech Inc | Iodine-type concentrated bactericidal composition |
| JP2005289866A (en) * | 2004-03-31 | 2005-10-20 | Kobayashi Pharmaceut Co Ltd | Liquid state composition and method for producing the same |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02115105A (en) * | 1988-10-24 | 1990-04-27 | Kao Corp | Sterilizing and disinfecting agent composition |
| JP2003183169A (en) * | 2001-12-19 | 2003-07-03 | Toho Earthtech Inc | Iodine-type concentrated bactericidal composition |
| JP2005289866A (en) * | 2004-03-31 | 2005-10-20 | Kobayashi Pharmaceut Co Ltd | Liquid state composition and method for producing the same |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115517267A (en) * | 2022-10-17 | 2022-12-27 | 岳阳渔美康生物科技有限公司 | High-distribution-coefficient compound iodine solution for breeding and preparation method thereof |
| CN115517267B (en) * | 2022-10-17 | 2023-06-16 | 岳阳渔美康生物科技有限公司 | Composite iodine solution with high partition coefficient for cultivation and preparation method thereof |
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