JPH01193387A - Method for stabilizing azulene compound - Google Patents
Method for stabilizing azulene compoundInfo
- Publication number
- JPH01193387A JPH01193387A JP63017615A JP1761588A JPH01193387A JP H01193387 A JPH01193387 A JP H01193387A JP 63017615 A JP63017615 A JP 63017615A JP 1761588 A JP1761588 A JP 1761588A JP H01193387 A JPH01193387 A JP H01193387A
- Authority
- JP
- Japan
- Prior art keywords
- amphoteric surfactant
- group
- guaiazulene
- sodium
- surfactant
- 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
- -1 azulene compound Chemical class 0.000 title claims abstract description 30
- CUFNKYGDVFVPHO-UHFFFAOYSA-N Azulene Natural products C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 238000000034 method Methods 0.000 title claims description 15
- 230000000087 stabilizing effect Effects 0.000 title claims description 4
- FWKQNCXZGNBPFD-UHFFFAOYSA-N Guaiazulene Chemical compound CC(C)C1=CC=C(C)C2=CC=C(C)C2=C1 FWKQNCXZGNBPFD-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229960002350 guaiazulen Drugs 0.000 claims abstract description 17
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000004471 Glycine Substances 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000002280 amphoteric surfactant Substances 0.000 claims description 33
- 150000001875 compounds Chemical class 0.000 claims description 8
- 230000006641 stabilisation Effects 0.000 claims description 7
- 238000011105 stabilization Methods 0.000 claims description 7
- 239000002253 acid Chemical group 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001340 alkali metals Chemical group 0.000 claims description 5
- 239000003945 anionic surfactant Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- FFMBYMANYCDCMK-UHFFFAOYSA-N 2,5-dihydro-1h-imidazole Chemical compound C1NCN=C1 FFMBYMANYCDCMK-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000002537 cosmetic Substances 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- 239000002563 ionic surfactant Substances 0.000 abstract 3
- 239000002184 metal Substances 0.000 abstract 3
- 238000004321 preservation Methods 0.000 abstract 1
- 150000003871 sulfonates Chemical class 0.000 abstract 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 230000000052 comparative effect Effects 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 235000011187 glycerol Nutrition 0.000 description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 150000001545 azulenes Chemical class 0.000 description 9
- 239000008213 purified water Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000003205 fragrance Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 229950002760 sodium gualenate Drugs 0.000 description 8
- GEYJUFBPCGDENK-UHFFFAOYSA-M sodium;3,8-dimethyl-5-propan-2-ylazulene-1-sulfonate Chemical compound [Na+].CC(C)C1=CC=C(C)C2=C(S([O-])(=O)=O)C=C(C)C2=C1 GEYJUFBPCGDENK-UHFFFAOYSA-M 0.000 description 8
- 239000004094 surface-active agent Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
- 239000003093 cationic surfactant Substances 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 235000010418 carrageenan Nutrition 0.000 description 5
- 239000000679 carrageenan Substances 0.000 description 5
- 229920001525 carrageenan Polymers 0.000 description 5
- 229940113118 carrageenan Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229960002449 glycine Drugs 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 5
- 239000000606 toothpaste Substances 0.000 description 5
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 5
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 4
- 239000002736 nonionic surfactant Substances 0.000 description 4
- VIZXMHCBZLGUET-UHFFFAOYSA-N sodium gualenate Chemical compound CC(C)C1=CC=C(C)C2=C(S(O)(=O)=O)C=C(C)C2=C1 VIZXMHCBZLGUET-UHFFFAOYSA-N 0.000 description 4
- 239000001540 sodium lactate Substances 0.000 description 4
- 235000011088 sodium lactate Nutrition 0.000 description 4
- 229940005581 sodium lactate Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 229940034610 toothpaste Drugs 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 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 3
- 239000007788 liquid Substances 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 3
- 229940042585 tocopherol acetate Drugs 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 2
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 2
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- HPJYKMSFRBJOSW-JHSUYXJUSA-N Damsin Chemical compound C[C@H]1CC[C@H]2C(=C)C(=O)O[C@H]2[C@]2(C)C(=O)CC[C@@H]12 HPJYKMSFRBJOSW-JHSUYXJUSA-N 0.000 description 2
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 2
- 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 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 239000005770 Eugenol Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 2
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229960003260 chlorhexidine Drugs 0.000 description 2
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 2
- 229960002217 eugenol Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000004482 other powder Substances 0.000 description 2
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 2
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 239000000344 soap Substances 0.000 description 2
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- ADOBXTDBFNCOBN-UHFFFAOYSA-N 1-heptadecene Chemical group CCCCCCCCCCCCCCCC=C ADOBXTDBFNCOBN-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- DCTOHCCUXLBQMS-UHFFFAOYSA-N 1-undecene Chemical group CCCCCCCCCC=C DCTOHCCUXLBQMS-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- WJLVQTJZDCGNJN-UHFFFAOYSA-N Chlorhexidine hydrochloride Chemical compound Cl.Cl.C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 WJLVQTJZDCGNJN-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000025157 Oral disease Diseases 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000003082 abrasive agent Substances 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 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
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960004504 chlorhexidine hydrochloride Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229960001378 dequalinium chloride Drugs 0.000 description 1
- LTNZEXKYNRNOGT-UHFFFAOYSA-N dequalinium chloride Chemical compound [Cl-].[Cl-].C1=CC=C2[N+](CCCCCCCCCC[N+]3=C4C=CC=CC4=C(N)C=C3C)=C(C)C=C(N)C2=C1 LTNZEXKYNRNOGT-UHFFFAOYSA-N 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000002845 discoloration Methods 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
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002335 preservative 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
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 108700004121 sarkosyl Proteins 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 230000021148 sequestering of metal ion Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 125000004436 sodium atom Chemical group 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940045885 sodium lauroyl sarcosinate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Detergent Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
Abstract
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は、アズレン化合物の安定化に関する。[Detailed description of the invention] [Industrial application field] The present invention relates to the stabilization of azulene compounds.
さらに詳細には、アズレン化合物に両性界面活性剤を配
合することにより、長期保存に耐え得るアズレン化合物
含有製剤を提供するものである。More specifically, by blending an azulene compound with an amphoteric surfactant, an azulene compound-containing preparation that can withstand long-term storage is provided.
［従来の技術およびその問題点コ
アズレン化合物は、消炎作用、抗菌作用、抗カビ作用、
抗アレルギー作用、組織再生性等を有し、また安全性が
高いこともあり広く製剤に応用されている。特に、皮膚
あるいは口腔内疾患の治療および予防に有効であり、歯
みがき、クリーム、ローション類、石鹸類等に配合され
ている。[Conventional technology and its problems Coazulene compounds have anti-inflammatory, antibacterial, antifungal,
It has anti-allergic effects, tissue regeneration properties, etc., and is highly safe, so it is widely used in pharmaceutical preparations. It is particularly effective in treating and preventing skin or oral diseases, and is incorporated into toothpastes, creams, lotions, soaps, and the like.
しかしながら、アズレン化合物は、光や空気中の酸素に
よって徐々に分解、退色することから、通常の製剤にア
ズレン化合物を配合しても、製品の色調が変化するとと
もに、薬効も低下してしまう等の欠点を有する。従来こ
れを防止するには、製剤を気密容器に入れ窒素置換する
方法がとられているが、容器の材質が制限され、また製
造工程が繁雑でコストアップとなる等の問題がある。However, azulene compounds gradually decompose and discolor due to exposure to light and oxygen in the air, so even if azulene compounds are added to regular formulations, the color tone of the product will change and the medicinal efficacy will decrease. It has its drawbacks. Conventionally, this has been prevented by placing the preparation in an airtight container and purging it with nitrogen, but there are problems such as restrictions on the material of the container and the complicated manufacturing process, which increases costs.
また、酸性に弱いということから、ＰＨを７以上に保つ
ことが行われているが、この方法では長期間の安定性は
必ずしも十分ではない。Furthermore, since it is susceptible to acidity, the pH is maintained at 7 or higher, but this method does not necessarily provide sufficient long-term stability.
その他、製剤に界面活性剤を添加することにより、安定
化する方法も行われている。特開昭５９−１９６８１６
号公報には、水溶性アズレン誘導体を含有する水溶液に
、カチオン性界面活性剤あるいはクロルヘキシジンのい
ずれか一方と非イオン性界面活性剤を添加する安定化方
法について記載されている。しかし、この方法では、調
製時における沈殿あるいは濁りの防止効果、防腐効果の
低下防止効果は得られるが、長期間安定性を°維持する
には必ずしも十分であるとは言えない。Other methods of stabilizing the formulation include adding a surfactant to the formulation. Japanese Patent Publication No. 59-196816
The publication describes a stabilization method in which either a cationic surfactant or chlorhexidine and a nonionic surfactant are added to an aqueous solution containing a water-soluble azulene derivative. However, although this method provides the effect of preventing precipitation or turbidity during preparation and the effect of preventing deterioration of preservative effect, it cannot necessarily be said to be sufficient to maintain long-term stability.
特開昭５１−１２５７１３号公報には、水溶性アズレン
誘導体を含有する水溶液に、テトラメチルアンモニウム
塩や逆性石鹸等のカチオン性界面活性剤を添加する安定
化方法について記載されている。しかし、カチオン性界
面活性剤は、アズレン化合物を長期間安定に維持するこ
とは難しいことが認められた。JP-A-51-125713 describes a stabilization method in which a cationic surfactant such as a tetramethylammonium salt or a reverse soap is added to an aqueous solution containing a water-soluble azulene derivative. However, it has been recognized that it is difficult for cationic surfactants to maintain azulene compounds stably for long periods of time.
［問題点を解決するための手段］
本発明者らは、前記の問題点を克服しアズレン化合物を
より効果的に利用するため、アズレン化合物の安定化に
関する研究を進めた結果、アズレン化合物に両性界面活
性剤を添加することにより、アズレン化合物の経時的分
解および退色を防止できることを見いだし、本発明を完
成するに至った。[Means for Solving the Problems] In order to overcome the above-mentioned problems and utilize azulene compounds more effectively, the present inventors have carried out research on the stabilization of azulene compounds. It has been discovered that by adding a surfactant, decomposition and discoloration of the azulene compound over time can be prevented, and the present invention has been completed.
本発明は、グアイアズレンおよびグアイアズレンスルホ
ン酸塩類よりなる群から選ばれたアズレン化合物に、両
性界面活性剤を配合することを特徴とするアズレン化合
物の安定化法である。The present invention is a method for stabilizing an azulene compound, which comprises blending an amphoteric surfactant with an azulene compound selected from the group consisting of guaiazulene and guaiazulene sulfonates.
ここで、アズレン化合物は１種に限らず２種以上でもよ
い。また、グアイアズレンスルホン酸の塩類としては、
ナトリウム塩、カリウム塩、アンモニウム塩等がある。Here, the number of azulene compounds is not limited to one type, and two or more types may be used. In addition, as salts of guaiazulene sulfonic acid,
There are sodium salts, potassium salts, ammonium salts, etc.
両性界面活性剤とは、イミダゾリン型両性界面活性剤お
よび／またはグリシン型両性界面活性剤である。The amphoteric surfactant is an imidazoline type amphoteric surfactant and/or a glycine type amphoteric surfactant.
（以下、余白）
イミダゾリン型両性界面活性剤とは、
（式中、Ｒはアルキル基またはアルケニル基を示し、Ｘ
は式Ｃ００Ｍ、ＣＨ，Ｃ００ＭまたはＣＨ（ＯＨ）ＣＨ
，ＳＯ，Ｍで表される基を示し、Ｙは水素原子、アルカ
リ金属原子または弐ＣＨ，Ｃ００Ｍで表される基を示し
、Ｇは水酸基、塩素原子または陰イオン性界面活性剤の
酸基を示す。また、Ｍは水素原子、アルカリ金属原子ま
たはアンモニウムを示す、）で示される化合物である。(Hereinafter, blank space) What is an imidazoline type amphoteric surfactant? (In the formula, R represents an alkyl group or an alkenyl group, and
is the formula C00M, CH, C00M or CH(OH)CH
, SO, M, Y represents a hydrogen atom, an alkali metal atom, or a group represented by 2CH, C00M, G represents a hydroxyl group, a chlorine atom, or an acid group of an anionic surfactant. show. Furthermore, M represents a hydrogen atom, an alkali metal atom, or ammonium.
ここで、アルカリ金属原子としては、ナトリウム原子、
カリウム原子等を挙げることができ、また陰イオン性界
面活性剤の酸基としては、スルホ基、スルホオキシ基、
ホルミルオキシ基、アセチルオキシ基、プロピオニルオ
キシ基、シトリル才キシ基等を挙げることができる。Here, the alkali metal atoms include sodium atoms,
Examples of the acid group of the anionic surfactant include a potassium atom, a sulfo group, a sulfooxy group,
Examples include formyloxy group, acetyloxy group, propionyloxy group, and citryloxy group.
本発明において、（Ｉ）式のＲが示すアルキル基として
は、炭素数９〜１７のものを挙げることができる。例え
ば、ウンデシル基、ペンタデシル基、トリデシル基等で
ある。またアルケニル基としては、炭素数９〜１８のも
のを挙げることができる。In the present invention, examples of the alkyl group represented by R in formula (I) include those having 9 to 17 carbon atoms. For example, undecyl group, pentadecyl group, tridecyl group, etc. Further, examples of the alkenyl group include those having 9 to 18 carbon atoms.
例えば、ウンデセン基、ヘプタデセン基等である。For example, undecene group, heptadecene group, etc.
グリシン型両性界面活性剤とは、アルキルジアミノエチ
ルグリジン塩酸塩または同アルカリ金属塩である。The glycine type amphoteric surfactant is alkyl diaminoethyl glycine hydrochloride or its alkali metal salt.
また、アルキルジアミノエチルグリシンのアルキル基と
しては炭素数８〜１８のものを挙げることができる。例
えば、ドデシル基、テトラデシル基、ヘキサデシル基等
である。Furthermore, examples of the alkyl group of alkyldiaminoethylglycine include those having 8 to 18 carbon atoms. For example, dodecyl group, tetradecyl group, hexadecyl group, etc.
このイミダゾリン型両性界面活性剤および／またはグリ
シン型両性界面活性剤の配合量は、製剤全量の０．１〜
２０重量％であり、好ましくは０．５〜２０重量％であ
る。また、これらの両性界面活性剤はいずれも酸性、中
性またはアルカリ性溶液中で使用することが可能である
。The amount of the imidazoline type amphoteric surfactant and/or glycine type amphoteric surfactant is 0.1 to
The amount is 20% by weight, preferably 0.5 to 20% by weight. Moreover, any of these amphoteric surfactants can be used in acidic, neutral or alkaline solutions.
この他、必要に応じて、金属イオン封鎖剤（ＥＤＴＡ、
ポリリン酸塩等）、抗酸化剤（ブチルヒドロキシアニソ
ール、ジブチルヒドロキシトルエン、ビタミンＥアセテ
ート等）、溶剤（グリセリン、エタノール、プロピレン
グリコール、１．３ブチシングリコール等）、界面活性
剤（カチオン性界面活性剤、アニオン性界面活性剤、非
イオン性界面活性剤等）、増粘剤（カラギーナン、カル
ボキシメチルセルロースナトリウム、アルギン酸ナトリ
ウム、メチルセルロース等）、研磨剤（次階カルシウム
、無水ケイ酸、水酸化アルミニウム、結晶セルロース等
）、発泡剤（ラウリル硫酸ナトリウム、ラウロイルザル
フシンナトリウム、ポリオキシエチレンソルビタンモノ
詣肪酸エステル等）等を本発明の効果を損わない範囲で
配合することができる。本発明の製剤は、内服剤および
外用剤として、液剤、乳液剤、クリーム剤、軟膏剤、ゲ
ル剤、エアゾール剤、懸濁剤、パップ剤等に調製するこ
とができる。In addition, metal ion sequestering agents (EDTA,
polyphosphates, etc.), antioxidants (butylated hydroxyanisole, dibutylated hydroxytoluene, vitamin E acetate, etc.), solvents (glycerin, ethanol, propylene glycol, 1.3-butysine glycol, etc.), surfactants (cationic surfactants) agents, anionic surfactants, nonionic surfactants, etc.), thickeners (carrageenan, sodium carboxymethylcellulose, sodium alginate, methylcellulose, etc.), abrasives (calcium, anhydrous silicic acid, aluminum hydroxide, crystals, etc.) Cellulose, etc.), foaming agents (sodium lauryl sulfate, sodium lauroyl zalfucin, polyoxyethylene sorbitan monofatty acid ester, etc.), etc. can be blended within a range that does not impair the effects of the present invention. The preparation of the present invention can be prepared as a liquid, emulsion, cream, ointment, gel, aerosol, suspension, poultice, etc. for internal use and external use.
［発明の効果］
本発明により、製剤を気密容器に入れ窒素置換する方法
、ＰＨを７以上に保つ方法、また製剤にアニオン性界面
活性剤、カチオン性界面活性剤もしくは非イオン性界面
活性剤単独またはカチオン性界面活性剤と非イオン性界
面活性剤を混合して添加する方法に比較し、グアイアズ
レンおよびグアイアズレンスルホン酸塩の長期安定性を
著しく高めた内服および外用の医薬品、医薬部外品およ
び化粧品を提供することが可能となった。[Effects of the invention] The present invention provides a method for placing a preparation in an airtight container and purging it with nitrogen, a method for maintaining the pH at 7 or higher, and a method for adding an anionic surfactant, a cationic surfactant, or a nonionic surfactant alone to the preparation. Or internal and external medicines, quasi-drugs, and cosmetics that have significantly improved long-term stability of guaiazulene and guaiazulene sulfonate compared to the method of adding a mixture of cationic surfactants and nonionic surfactants. It became possible to provide.
［実施例］
以下、実施例および試験例を挙げて発明を具体的に説明
する。[Example] Hereinafter, the invention will be specifically explained with reference to Examples and Test Examples.
実施例１［練歯磨コ
グアイアズレンスルホン酸ナトリウム ０．０２ ｇ酸
化チタン ２．０ｇラウリル
硫酸ナトリウム １．５ｇラウロイルザル
コシンナトリウム ０．３ｇ無水ケイ酸
１５．０ ｇ濃グリセリン
３０．０ ｇ乳酸ナトリウム
５．０ｇカラギーナン
０．７ｇカルボキシメチルセルロースナトリウムパ
ラオキシ安息香酸エチル ｏ． ｏｓ ｇパラ
オキシ安息香酸プロピル ｏ． ｏｓ ｇサッカ
リンナトリウム ０．１ｇ水酸化ナトリ
ウム ０．２８ｇエチレンジアミン
四酢酸二ナトリウム ０． ０５ ｇジブチルヒドロキ
シトルエン ｏ． ｏｓ ｇ塩化デカリニウム
０． ０２ ｇ香料
０． ９５ ｇイミダゾリン型両性
界面活性剤（注１）６、０ｇ精製水
全量１００ｇカラギーナンおよびカルボキシメ
チルセルロースナトリウム
に濃グリセリンおよび乳酸ナトリウムの液体成分を入れ
、きらに無水ケイ酸、ラウリル硫酸ナトリウムおよびラ
ウロイルザルフシンナトリウム、その他の粉末成分を篩
過したものを入れ、最後にグアイアズレンスルホン酸ナ
トリウムを入れ混合攪拌した後、真空脱泡し、練歯磨を
製造した。Example 1 [Toothpaste Sodium coguaiazulene sulfonate 0.02 g Titanium oxide 2.0 g Sodium lauryl sulfate 1.5 g Sodium lauroyl sarcosine 0.3 g Silicic anhydride
15.0 g concentrated glycerin
30.0 g sodium lactate
5.0g carrageenan
0.7g Sodium carboxymethyl cellulose Ethyl paraoxybenzoate o. os gPropyl paraoxybenzoate o. os g Sodium saccharin 0.1 g Sodium hydroxide 0.28 g Disodium ethylenediaminetetraacetate 0. 05 g dibutylhydroxytoluene o. os g dequalinium chloride 0. 02g fragrance
0. 95 g imidazoline type amphoteric surfactant (Note 1) 6.0 g purified water
Add the liquid ingredients of concentrated glycerin and sodium lactate to the total amount of 100g carrageenan and sodium carboxymethyl cellulose, add the sieved silicic anhydride, sodium lauryl sulfate, sodium lauroyl zalfucine, and other powder ingredients to the glass, and finally add the guaiazulene sulfone. After adding sodium chloride and stirring, vacuum defoaming was performed to produce a toothpaste.
（注１）（１）式において、Ｒ＝Ｃ，、Ｈ，、、Ｘ＝Ｃ
０ＯＮａ、Ｙ＝ＣＨｔＣＯＯＮａ。(Note 1) In formula (1), R=C,,H,,,X=C
0ONa, Y=CHtCOONa.
Ｇ＝ＯＨの化合物
実施例２［練歯磨コ
グアイアズレン ０．０２ｇビタ
ミンＥアセテ−） ０．１ｇ酸化チ
タン ２．０ｇラウリル硫
酸ナトリウム １．５ｇラウロイルザルコ
シンナトリウム ０．３ｇ無水ケイ酸
１５．０ ｇ濃グリセリン
３０．０ ｇ乳酸ナトリウム
５．０ｇカラギーナン
０．７ｇカルボキシメチルセルロースナトリウムバラオ
キシ安息香酸エチル ｏ． ｏｓ ｇバラオキ
ジ安息香酸プロピル ０． ０５ ｇサッカリン
ナトリウム ０．１ｇ塩酸クロルヘキシ
ジン ０．０２ｇエチレンジアミン四酢
酸二ナトリウム ０． ０５ ｇジブチルヒドロキシト
ルエン ｏ． ｏｓ ｇ香料
０． ９５ ｇグリシン型両性界面活性
剤（注２） ３．０ｇ精製水
全量１００ｇカラギーナンおよびカルボキシメチ
ルセルロースナトリウム
中に濃グリセリンおよび乳酸ナトリウムの液体成分を入
れ、さらに無水ケイ酸、ラウリル硫酸ナトリウムおよび
ラウロイルザルコシンナトリウム、およびその他の粉末
成分を篩過したものを添加混合し、最後にグアイアズレ
ンをビタミンＥアセテート中に溶解したものを入れ混合
攪拌した後、真空脱泡し、練歯磨を製造した。Compound Example 2 of G=OH [Toothpaste Coguaiazulene 0.02g Vitamin E acetate] 0.1g Titanium oxide 2.0g Sodium lauryl sulfate 1.5g Sodium lauroyl sarcosinate 0.3g Silicic anhydride
15.0 g concentrated glycerin
30.0 g sodium lactate
5.0g carrageenan
0.7g sodium carboxymethyl cellulose ethyl oxybenzoate o. os g Propyl roseate benzoate 0. 05 g Sodium saccharin 0.1 g Chlorhexidine hydrochloride 0.02 g Disodium ethylenediaminetetraacetate 0. 05 g dibutylhydroxytoluene o. os g fragrance
0. 95 g Glycine type amphoteric surfactant (Note 2) 3.0 g Purified water
Add the liquid components of concentrated glycerin and sodium lactate to a total of 100 g of carrageenan and sodium carboxymethylcellulose, and then add and mix silicic anhydride, sodium lauryl sulfate, sodium lauroyl sarcosine, and other powder components that have been sieved, and finally. A solution of guaiazulene in vitamin E acetate was mixed and stirred, followed by vacuum defoaming to produce a toothpaste.
（注２） ドデシルジアミノエチルグリシン塩酸塩−テ
トラデシルジアミノエチル
グリシン塩酸塩 ６：４（重量比）
混合物
実施例３［クリ−ムコ
ステアリン酸 １５．０ｇ流動
パラフィン ５．０ｇセタノール
１．０ｇ水酸化カリウム
０．７ｇポリオキシエチレンソル
ビタンモノ
ステアレート ２，０ｇプロピ
レングリコール ｉｏ． ｏ ｇグリセ
リン ５．０ｇイミダゾリン型
両性界面活性剤（注３）３．０ｇグアイアズレン
０．０２ｇグアイアズレンスルホン酸ナ
トリウム ０． ０１ ｇ香料
０．３ｇ精製水
全量１００ｇ８２℃に加熱溶解したステアリン酸、流動
パラフィンおよびセタノールを攪拌しながら、８０℃に
加熱溶解した水酸化カリウム、ポリオキシエチレンソル
ビクンモノステアレート、プロピレングリフール、グリ
セリンおよびイミダゾリン型両性界面活性剤に、徐々に
混合して乳化を行った。その後放冷し、５０℃になって
から香料にグアイアズレンおよびグアイアズレンスルホ
ン酸ナトリウムを溶解したものを添加し、さらに３０℃
まで冷却しクリームを製造した。(Note 2) Dodecyldiaminoethylglycine hydrochloride - Tetradecyldiaminoethylglycine hydrochloride 6:4 (weight ratio) Mixture Example 3 [Cream costearic acid 15.0g Liquid paraffin 5.0g Setanol 1.0g Potassium hydroxide
0.7g polyoxyethylene sorbitan monostearate 2.0g propylene glycol io. o g Glycerin 5.0 g Imidazoline type amphoteric surfactant (Note 3) 3.0 g Guaiazulene
0.02g Sodium guaiazulene sulfonate 0. 01g fragrance
0.3g purified water
Total amount 100g While stirring stearic acid, liquid paraffin and cetanol heated and dissolved at 82℃, potassium hydroxide, polyoxyethylene sorbicun monostearate, propylene glyfur, glycerin and imidazoline type amphoteric surfactant dissolved at 80℃. Then, the mixture was gradually mixed and emulsified. After that, it was left to cool, and when the temperature reached 50°C, a solution of guaiazulene and sodium guaiazulene sulfonate was added to the fragrance, and the temperature was further increased to 30°C.
The mixture was cooled to a temperature of 50°C to produce cream.
（注３）（１）式において、ＲミＣ＊Ｈ＋ｅ，Ｘ＝ＣＨ
．ＣＯＯＮａ 、Ｙ＝ＣＨ−Ｃｏ。(Note 3) In formula (1), RmiC*H+e, X=CH
．． COONa, Y=CH-Co.
Ｎａ 、Ｇ＝ＯＨの化合物
実施例４［化粧水コ
エタノール １０． ０ ｇ
ポリオキシエチレンソルビタンモノラ
ウレート １、Ｏｇパラ
オキシ安息香酸メチル ０．２ｇ香料
０．２ｇグアイアズレンス
ルホン酸カリウム ０． ０２ ｇグリセリン
５．０ｇイミダゾリン型両性界面活
性剤（注４）５．０ｇ１、３−ブチレングリコール
６．０ｇ精製水
全量１００ｇ室温にて、グアイアズレンスルホン酸カリ
ウム、グリセリン、イミダゾリン型両性界面活性剤およ
び１．３−ブチレンゲリコールを精製水に攪拌溶解し、
この中に室温にて、ポリオキシエチレンソルビタンモノ
ラウレート、バラオキシ安息香酸メチルおよび香料をエ
タノールに攪拌溶解したものを徐々に添加して可溶化し
た後、濾過して化粧水を製造した。Compound Example 4 of Na, G=OH [Lotion coethanol 10. 0 g
Polyoxyethylene sorbitan monolaurate 1, Og methyl paraoxybenzoate 0.2g fragrance
0.2g potassium guaiazulene sulfonate 0. 02g glycerin
5.0g imidazoline type amphoteric surfactant (Note 4) 5.0g 1,3-butylene glycol
6.0g purified water
Potassium guaiazulene sulfonate, glycerin, imidazoline type amphoteric surfactant and 1,3-butylene gellicol were dissolved in purified water with stirring at room temperature, total amount 100 g.
A solution obtained by stirring and dissolving polyoxyethylene sorbitan monolaurate, methyl roseoxybenzoate, and fragrance in ethanol was gradually added to the mixture at room temperature to solubilize the mixture, and the mixture was filtered to produce a lotion.
（注４）（Ｉ）式において、Ｒ＝Ｃ，、Ｈ，、、Ｘ＝Ｃ
０ＯＮａ 、Ｙ−Ｈ，Ｇ−ＯＨの
化合物
実施例５［含獣剤コ
ゲルコン酸クロルヘキシジン ０．８ｇグア
イアズレンスルホン酸ナトリウム ０．０５ ｇメント
ール １．０ｇオイゲノー
ル １．０ｇエタノール
３０．０ ｇポリオキシエチレン硬
化ヒマシ油 ５．Ｏｇイミダゾリン型型性性界面活
性剤注５）６、Ｏｇグリシン型型性性界面活性剤注６）
６．０ｇサッカリンナトリウム
０．１ｇソルビット １
０．０ｇ精製水 全量１００ｇ
メントールおよびオイゲノールをエタノールに溶解し、
あらかじめ精製水にその他の添加物を溶解しておいたも
のに添加混合した後、綿栓濾過して製造した。(Note 4) In formula (I), R=C,,H,,,X=C
Compound Example 5 of 0ONa, Y-H, G-OH [Animal-containing agent Chlorhexidine cogelconate 0.8 g Sodium guaiazulene sulfonate 0.05 g Menthol 1.0 g Eugenol 1.0 g Ethanol
30.0 g polyoxyethylene hydrogenated castor oil 5. Og imidazoline type surfactant Note 5) 6, Og glycine type surfactant Note 6)
6.0g saccharin sodium
0.1g sorbitol 1
0.0g purified water total amount 100g
Dissolve menthol and eugenol in ethanol,
It was produced by adding and mixing other additives dissolved in purified water in advance and filtering the mixture through a cotton plug.
（注５）（Ｉ）式におイテ、Ｒ−ＣｚＨｔ、、Ｘ＝Ｃ０
ＯＮａ 、Ｙ−Ｈ，Ｇ＝ＯＨの
化合物
（注６） ドデシルジアミノエチルグリシン塩酸塩−テ
トラデシルジアミノエチル
グリシン塩酸塩 ６：４（重量比）
混合物
実施例６［クリ−ムコ
ステアリン酸 ｉｏ、 ｏ ｇ
流動パラフィン １０．０ ｇセタ
ノール ２．０ｇ水酸化カリ
ウム ０．７ｇポリオキシエチレ
ンソルビタンモノ
ステアレート ２．０ｇプロ
ピレングリフール ９．０ｇグリセリン
５．０ｇイミダゾリン型両性
界面活性剤（注７）３．０ｇグアイアズレン
０．０２ｇ香料
０．３ｇ精製水 全
量１００ｇ実施例３と同様にして、クリームを製造した
。(Note 5) According to formula (I), R-CzHt, , X=C0
Compound of ONa, Y-H, G=OH (Note 6) Dodecyldiaminoethylglycine hydrochloride-tetradecyldiaminoethylglycine hydrochloride 6:4 (weight ratio) Mixture Example 6 [Cream costearic acid io, o g
Liquid paraffin 10.0 g Setanol 2.0 g Potassium hydroxide 0.7 g Polyoxyethylene sorbitan monostearate 2.0 g Propylene glyfur 9.0 g Glycerin 5.0 g Imidazoline type amphoteric surfactant (Note 7) 3.0 g Guaiazulene
0.02g fragrance
0.3 g Purified water Total amount 100 g A cream was produced in the same manner as in Example 3.
（注７）＜１＞式において、Ｒ−ＣｅＨｒｅ 、Ｘ −
ＣＨ，Ｃ０ＯＨ，Ｙ−ＣＨ，Ｃ０ＯＨ。(Note 7) In formula <1>, R-CeHre, X-
CH, COOH, Y-CH, COOH.
Ｇ＝ＣＩの化合物
実施例７［化粧水コ
エタノール １５．０ ｇポ
リオキシエチレンソルビタンモノラ
ウレート １．０ｇバラオ
キシ安息香酸メチル ０．２ｇ香料
０．２ｇグアイアズレンスル
ホン酸カリウム ０．０２ ｇグリセリン
３．０ｇイミダゾリン型両性界面活性
剤（注８）５．０ｇ１．３−ブチレンゲリコール
３．０ｇ精製水 全
量１００ｇ実施例４と同様にして、化粧水を製造した。Compound Example 7 where G=CI [Lotion coethanol 15.0 g Polyoxyethylene sorbitan monolaurate 1.0 g Methyl roseoxybenzoate 0.2 g Fragrance
0.2g potassium guaiazulene sulfonate 0.02g glycerin
3.0g imidazoline type amphoteric surfactant (Note 8) 5.0g 1.3-butylene gellicol
3.0g purified water Total amount 100g A lotion was produced in the same manner as in Example 4.
（注８）（Ｉ）式において、Ｒ＝ Ｃ＋ｔＨｓａ、 Ｘ
＝Ｃ０ＯＨ、Ｙ＝Ｈ、Ｇ＝Ｈ３Ｏ，の化
合物
試験例
［試料の調製コ
試料１〜９
両性界面活性剤と０．０２重量部のグアイアズレンスル
ホン酸ナトリウムの混合物に、ＰＨ８の０６１Ｍリン酸
緩衝液を入れ１００重量部に調製し、５０°Ｃの恒温室
中に保管し、これらを試料１〜９とした。なお、各試料
における両性界面活性剤の種類と配合量は表１に示す通
りである。(Note 8) In formula (I), R = C + tHsa, X
=C0OH, Y=H, G=H3O, Compound Test Example [Sample Preparation Samples 1 to 9 A mixture of an amphoteric surfactant and 0.02 parts by weight of sodium guaiazulene sulfonate was added to a 061M phosphate buffer with a pH of 8. were prepared to 100 parts by weight and stored in a thermostatic chamber at 50°C, and these were designated as Samples 1 to 9. The type and amount of amphoteric surfactant in each sample are shown in Table 1.
試料１０〜１８
グアイアズレンスルホン酸ナトリウムの代わりに０．０
２重量部のグアイアズレン、０．４重量ｕｔｙ＞ポリオ
キシエチレン硬化ヒマシ油および２重量部のエタノール
を使用するほかは試料１〜９と同様にして試料１０〜
１８を得た。なお、各試料における両性界面活性剤の種
類と配合量は表２に示す通りである。Samples 10-18 0.0 instead of sodium guaiazulene sulfonate
Samples 10 to 9 were prepared in the same manner as Samples 1 to 9, except that 2 parts by weight of guaiazulene, 0.4 parts by weight of polyoxyethylene hydrogenated castor oil, and 2 parts by weight of ethanol were used.
I got 18. The type and amount of amphoteric surfactant in each sample are shown in Table 2.
［比較剤の調製コ
両性界面活性剤以外の界面活性剤を用いた場合を比較剤
とした。[Preparation of Comparative Agent] A comparative agent was prepared using a surfactant other than an amphoteric surfactant.
比較剤１
両性界面活性剤の代わりに、５．０重量部の塩化ベンザ
ルコニウムを使うほかは試料１〜９と同様にして比較剤
１を得た。Comparative Agent 1 Comparative Agent 1 was obtained in the same manner as Samples 1 to 9 except that 5.0 parts by weight of benzalkonium chloride was used instead of the amphoteric surfactant.
比較剤２
両性界面活性剤の代わりに、５．０重量部の塩化ベンザ
ルコニウムおよび５．０重量部のポリオキシエチレン（
２０）ソルビタンモノオレートをイ吏うほかは試料１〜
９と同様にして比較剤２を得た。Comparative Agent 2 Instead of the amphoteric surfactant, 5.0 parts by weight of benzalkonium chloride and 5.0 parts by weight of polyoxyethylene (
20) Sample 1~ except for adding sorbitan monooleate
Comparative agent 2 was obtained in the same manner as in Example 9.
比較剤３
両性界面活性剤の代わりに、５．０重量部のポリオキシ
エチレン（２０）ソルビタンモノオレートを使うほかは
試料１〜９と同様にして比較剤３を得た。Comparative Agent 3 Comparative Agent 3 was obtained in the same manner as Samples 1 to 9, except that 5.0 parts by weight of polyoxyethylene (20) sorbitan monooleate was used instead of the amphoteric surfactant.
比較剤４
両性界面活性剤の代わりに、５．０重量部のラウリル硫
酸ナトリウムを使うほかは試料１〜９と同様にして比較
剤４を得た。Comparative Agent 4 Comparative Agent 4 was obtained in the same manner as Samples 1 to 9 except that 5.0 parts by weight of sodium lauryl sulfate was used instead of the amphoteric surfactant.
比較剤５〜８
グアイアズレンスルホン酸ナトリウムの代わりに０．０
２重量部のグアイアズレン、０．４重量部のポリオキシ
エチレン硬化ヒマシ油および２重量部のエタノールを使
用するほかは比較剤１〜４と同様にして比較剤５〜８を
得た。Comparative agent 5-8 0.0 in place of sodium guaiazulene sulfonate
Comparative Agents 5 to 8 were obtained in the same manner as Comparative Agents 1 to 4, except that 2 parts by weight of guaiazulene, 0.4 parts by weight of polyoxyethylene hydrogenated castor oil, and 2 parts by weight of ethanol were used.
［試験例１］
試料１〜９および比較剤１〜４の溶液中のアズレン化合
物を経時的に液体クロマトグラフ法［長さ１５０ｍｍ
、直径４ｍｏ＋のカラム、ＴＳＫ−ＧｅｌＬＳ４１０（
商品名、東洋ソーダ（株）製）を用い、カラム温度は４
０℃で、移動層には、アセトニトリル：０．０１Ｍ酢酸
ナトリウム：塩化ベンゼトニウム ５００ ： ５００
： ４の混液を用いた。］により、３０５ｎｍのＵＶ
吸収を測定し、グアイアズレンスルホン酸ナトリウムの
残存量を求め、残存率を算出した。また、コントロール
として、界面活性剤を入れない溶液を調製し、同様の試
験を行った。[Test Example 1] The azulene compounds in the solutions of Samples 1 to 9 and Comparative Agents 1 to 4 were analyzed over time by liquid chromatography [length 150 mm]
, 4 mo+ diameter column, TSK-Gel LS410 (
(trade name, manufactured by Toyo Soda Co., Ltd.) was used, and the column temperature was 4.
At 0°C, the mobile phase contained acetonitrile: 0.01 M sodium acetate: benzethonium chloride 500:500.
: A mixture of 4 was used. ], 305nm UV
Absorption was measured, the remaining amount of sodium guaiazulene sulfonate was determined, and the residual rate was calculated. In addition, as a control, a solution containing no surfactant was prepared and the same test was conducted.
［試験例２］
試料１０〜１８および比較剤５゛〜８の溶液中のアズレ
ン化合物を経時的に液体クロマトグラフ法［長さ１５０
ｍｍ 、直径４ｍｍのカラム、ＴＳＫ−Ｇｅ ＩＬＳ４
１０（商品名、東洋ソーダ（株）製）を用い、カラム温
度は５０℃で、移動層には、０．１％リン酸：メタノー
ル ２：８の混液を用いた。コにより、２８０ｎｍのＵ
Ｖ吸収を測定し、グアイアズレンの残存量を求め、残存
率を算出した。また、フントロールとして、界面活性剤
を入れない溶液を調製し、同様の試験を行った。[Test Example 2] Azulene compounds in solutions of Samples 10 to 18 and Comparative Agents 5 to 8 were analyzed over time by liquid chromatography [length 150
mm, 4 mm diameter column, TSK-Ge ILS4
10 (trade name, manufactured by Toyo Soda Co., Ltd.), the column temperature was 50° C., and the moving phase was a 2:8 mixture of 0.1% phosphoric acid and methanol. 280nm U
The V absorption was measured, the residual amount of guaiazulene was determined, and the residual rate was calculated. In addition, a similar test was conducted using a solution containing no surfactant as Funtrol.
両性界面活性剤添加による、効果を表１〜４に示す０表
１および表３を比較すると、グアイアズレンスルホン酸
ナトリウムの安定性が、さらに表２および表４を比較す
ると、グアイアズレンの安定性が長期にわたって保たれ
ていることは明らかである。The effects of adding an amphoteric surfactant are shown in Tables 1 to 4. Comparing Tables 1 and 3 shows that the stability of sodium guaiazulene sulfonate is higher, and comparing Tables 2 and 4 shows that the long-term stability of guaiazulene is higher. It is clear that it has been maintained for a long time.
Claims (1)
塩類よりなる群から選ばれたアズレン化合物に、両性界
面活性剤を配合することを特徴とするアズレン化合物の
安定化法。（２）両性界面活性剤が、イミダゾリン型両
性界面活性剤および／またはグリシン型両性界面活性剤
である特許請求の範囲第１項記載の安定化法。 （３）イミダゾリン型両性界面活性剤が、 一般式（ I ）、 ▲数式、化学式、表等があります▼（ I ） （式中、Ｒはアルキル基またはアルケニル基を示し、Ｘ
は式ＣＯＯＭ、ＣＨ＿２ＣＯＯＭまたはＣＨ（ＯＨ）Ｃ
Ｈ＿２ＳＯ＿３Ｍで表される基を示し、Ｙは水素原子、
アルカリ金属原子または式ＣＨ＿２ＣＯＯＭで表される
基を示し、Ｇは水酸基、塩素原子または陰イオン性界面
活性剤の酸基を示す。 また、Ｍは水素原子、アルカリ金属原子またはアンモニ
ウムを示す。）で示される化合物である特許請求の範囲
第２項記載の安定化法。 （４）グリシン型両性界面活性剤が、アルキルジアミノ
エチルグリシン塩酸塩または同アルカリ金属塩である特
許請求の範囲第２項記載の安定化法。[Scope of Claims] (1) A method for stabilizing an azulene compound, which comprises blending an amphoteric surfactant into an azulene compound selected from the group consisting of guaiazulene and guaiazulene sulfonates. (2) The stabilization method according to claim 1, wherein the amphoteric surfactant is an imidazoline type amphoteric surfactant and/or a glycine type amphoteric surfactant. (3) Imidazoline type amphoteric surfactants have the general formula (I), ▲mathematical formula, chemical formula, table, etc.▼(I) (wherein, R represents an alkyl group or an alkenyl group, and
is the formula COOM, CH_2COOM or CH(OH)C
Indicates a group represented by H_2SO_3M, Y is a hydrogen atom,
It represents an alkali metal atom or a group represented by the formula CH_2COOM, and G represents a hydroxyl group, a chlorine atom, or an acid group of an anionic surfactant. Moreover, M represents a hydrogen atom, an alkali metal atom or ammonium. ) The stabilization method according to claim 2, which is a compound represented by: (4) The stabilization method according to claim 2, wherein the glycine type amphoteric surfactant is alkyldiaminoethylglycine hydrochloride or an alkali metal salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1761588A JP2505513B2 (en) | 1988-01-28 | 1988-01-28 | Stabilization method for azulene compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1761588A JP2505513B2 (en) | 1988-01-28 | 1988-01-28 | Stabilization method for azulene compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01193387A true JPH01193387A (en) | 1989-08-03 |
| JP2505513B2 JP2505513B2 (en) | 1996-06-12 |
Family
ID=11948784
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1761588A Expired - Fee Related JP2505513B2 (en) | 1988-01-28 | 1988-01-28 | Stabilization method for azulene compounds |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2505513B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005035992A (en) * | 2003-06-26 | 2005-02-10 | Nippon Shinyaku Co Ltd | Dimethyl isopropyl azulene-containing external preparation |
| JP2014162725A (en) * | 2013-02-21 | 2014-09-08 | Sunstar Inc | External composition |
| CN112694443A (en) * | 2019-10-22 | 2021-04-23 | 中国石油化工股份有限公司 | Alkyl imidazoline polyether sulfonate surfactant and preparation method thereof |
-
1988
- 1988-01-28 JP JP1761588A patent/JP2505513B2/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005035992A (en) * | 2003-06-26 | 2005-02-10 | Nippon Shinyaku Co Ltd | Dimethyl isopropyl azulene-containing external preparation |
| JP2014162725A (en) * | 2013-02-21 | 2014-09-08 | Sunstar Inc | External composition |
| CN112694443A (en) * | 2019-10-22 | 2021-04-23 | 中国石油化工股份有限公司 | Alkyl imidazoline polyether sulfonate surfactant and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2505513B2 (en) | 1996-06-12 |
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