JP7654207B2 - Mouthwash - Google Patents
Mouthwash Download PDFInfo
- Publication number
- JP7654207B2 JP7654207B2 JP2023048809A JP2023048809A JP7654207B2 JP 7654207 B2 JP7654207 B2 JP 7654207B2 JP 2023048809 A JP2023048809 A JP 2023048809A JP 2023048809 A JP2023048809 A JP 2023048809A JP 7654207 B2 JP7654207 B2 JP 7654207B2
- Authority
- JP
- Japan
- Prior art keywords
- mouthwash
- hydrogenated castor
- polyoxyethylene hydrogenated
- castor oil
- concentrate
- 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.)
- Active
Links
- 239000002324 mouth wash Substances 0.000 title claims description 193
- 229940051866 mouthwash Drugs 0.000 title claims description 175
- -1 glycerin fatty acid ester Chemical class 0.000 claims description 116
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 66
- 239000004359 castor oil Substances 0.000 claims description 62
- 235000019438 castor oil Nutrition 0.000 claims description 54
- 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 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 42
- 239000000796 flavoring agent Substances 0.000 claims description 40
- 229960004830 cetylpyridinium Drugs 0.000 claims description 33
- NEUSVAOJNUQRTM-UHFFFAOYSA-N cetylpyridinium Chemical compound CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NEUSVAOJNUQRTM-UHFFFAOYSA-N 0.000 claims description 33
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 32
- 239000000194 fatty acid Substances 0.000 claims description 32
- 229930195729 fatty acid Natural products 0.000 claims description 32
- 235000013355 food flavoring agent Nutrition 0.000 claims description 30
- KKEMWYNNTBRYMR-UHFFFAOYSA-N azulene-1-sulfonic acid Chemical compound C1=CC=CC=C2C(S(=O)(=O)O)=CC=C21 KKEMWYNNTBRYMR-UHFFFAOYSA-N 0.000 claims description 23
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 claims description 21
- 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 claims description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
- 229920002678 cellulose Polymers 0.000 claims description 18
- 235000010980 cellulose Nutrition 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 235000011187 glycerol Nutrition 0.000 claims description 17
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 15
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 15
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 14
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 14
- 229960003943 hypromellose Drugs 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 13
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 13
- 229920000053 polysorbate 80 Polymers 0.000 claims description 13
- 229940068968 polysorbate 80 Drugs 0.000 claims description 13
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 12
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 12
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 12
- 229940085605 saccharin sodium Drugs 0.000 claims description 11
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 9
- 229960004998 acesulfame potassium Drugs 0.000 claims description 9
- 239000000619 acesulfame-K Substances 0.000 claims description 9
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 229960003237 betaine Drugs 0.000 claims 1
- 230000000052 comparative effect Effects 0.000 description 82
- 239000012141 concentrate Substances 0.000 description 66
- 239000013078 crystal Substances 0.000 description 46
- 238000001556 precipitation Methods 0.000 description 43
- 238000005187 foaming Methods 0.000 description 41
- 238000010790 dilution Methods 0.000 description 35
- 239000012895 dilution Substances 0.000 description 35
- 238000011156 evaluation Methods 0.000 description 33
- 230000001629 suppression Effects 0.000 description 28
- 238000012360 testing method Methods 0.000 description 27
- 150000005846 sugar alcohols Polymers 0.000 description 19
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
- 230000005764 inhibitory process Effects 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000002425 crystallisation Methods 0.000 description 14
- 230000008025 crystallization Effects 0.000 description 14
- 238000009472 formulation Methods 0.000 description 13
- 238000003756 stirring Methods 0.000 description 11
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 235000019634 flavors Nutrition 0.000 description 10
- 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 10
- 239000011550 stock solution Substances 0.000 description 10
- 239000006260 foam Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000008213 purified water Substances 0.000 description 8
- 239000000654 additive Substances 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000002562 thickening agent Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000000873 masking effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 150000004677 hydrates Chemical class 0.000 description 4
- 235000019640 taste Nutrition 0.000 description 4
- 206010006326 Breath odour Diseases 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000019658 bitter taste Nutrition 0.000 description 3
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 3
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 229960004949 glycyrrhizic acid Drugs 0.000 description 3
- 235000019410 glycyrrhizin Nutrition 0.000 description 3
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 3
- 229940070765 laurate Drugs 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000003002 pH adjusting agent Substances 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 150000003505 terpenes Chemical class 0.000 description 3
- 235000007586 terpenes Nutrition 0.000 description 3
- 238000011179 visual inspection Methods 0.000 description 3
- 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 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 229920002884 Laureth 4 Polymers 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 201000007100 Pharyngitis Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 229940068965 polysorbates Drugs 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 235000019615 sensations Nutrition 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- 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 1
- 241000723346 Cinnamomum camphora Species 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010034829 Pharyngeal oedema Diseases 0.000 description 1
- 229920001363 Polidocanol Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000996 additive effect Effects 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
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
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- 239000003899 bactericide agent Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 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
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- JHECKPXUCKQCSH-UHFFFAOYSA-J calcium;disodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate;hydrate Chemical compound O.[Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O JHECKPXUCKQCSH-UHFFFAOYSA-J 0.000 description 1
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- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
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- 238000012937 correction Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
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- 235000019800 disodium phosphate Nutrition 0.000 description 1
- LVXHNCUCBXIIPE-UHFFFAOYSA-L disodium;hydrogen phosphate;hydrate Chemical compound O.[Na+].[Na+].OP([O-])([O-])=O LVXHNCUCBXIIPE-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
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- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
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- 239000010643 fennel seed oil Substances 0.000 description 1
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- 235000019322 gelatine Nutrition 0.000 description 1
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- 208000007565 gingivitis Diseases 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
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- 238000005469 granulation Methods 0.000 description 1
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- 229940053336 lauromacrogols Drugs 0.000 description 1
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
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- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 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 1
- 239000001540 sodium lactate Substances 0.000 description 1
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- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
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- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明はアズレンスルホン酸及び／又はその塩を含むうがい薬（含嗽剤）に関する。 The present invention relates to a mouthwash (gargle) containing azulene sulfonic acid and/or its salt.
アズレンスルホン酸及びその塩は、従来より抗炎症剤として汎用され、これを希釈させた水溶液でうがいをすることにより、扁桃炎、咽頭炎、口内炎、歯肉炎を鎮める効果が知られている。 Azulene sulfonic acid and its salts have traditionally been widely used as anti-inflammatory agents, and gargling with a diluted aqueous solution of this is known to have the effect of soothing tonsillitis, pharyngitis, stomatitis, and gingivitis.
うがい薬には、のどのはれを抑えるアズレンスルホン酸及び／又はその塩等の抗炎症剤、口中やのどの粘膜で細菌の増殖を抑えるセチルピリジニウム及び／又はその塩等の殺菌剤、そして口中に清涼感を与え、口臭除去の効果を有するｌ－メントール等のテルペン類が配合されることが多い。
これらのうち、アズレンスルホン酸及び／又はその塩とセチルピリジニウム及び／又はその塩を同時に配合すると使用時の泡立ちが大きく、アズレンスルホン酸及び／又はその塩とｌ－メントール等のテルペン類を同時に配合するとこれら一方又は双方の結晶が析出し、さらに、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩とｌ－メントール等のテルペン類を同時に配合すると使用時に液垂れし、しかも使用感（含嗽時の風味）が悪いことが問題であった。
Mouthwashes often contain anti-inflammatory agents such as azulene sulfonic acid and/or its salts, which reduce throat swelling; bactericides such as cetylpyridinium and/or its salts, which reduce bacterial growth in the mucous membranes of the mouth and throat; and terpenes such as l-menthol, which provide a cooling sensation in the mouth and remove bad breath.
Among these, when azulene sulfonic acid and/or its salts are combined with cetylpyridinium and/or its salts, large amounts of foam are produced during use, and when azulene sulfonic acid and/or its salts are combined with terpenes such as l-menthol, crystals of one or both of these compounds are precipitated. Furthermore, when azulene sulfonic acid and/or its salts, cetylpyridinium and/or its salts are combined with terpenes such as l-menthol, dripping occurs during use and the feel when used (flavor when gargling) is poor.
前記の泡立ちについて、抗炎症作用が知られているグリチルリチン酸又はその塩を、発泡抑制剤としてうがい薬に配合した提案がなされている（特許文献１）。前記提案では、グリチルリチン酸又はその塩が矯味剤や甘味剤として医薬品に添加される旨の記載があるが、うがい薬の使用感（風味）を改善する程の十分な矯味性がグリチルリチン酸又はその塩にあるとは言い難い。 Regarding the foaming, it has been proposed to incorporate glycyrrhizinic acid or its salts, which are known to have anti-inflammatory effects, into mouthwash as a foaming inhibitor (Patent Document 1). The proposal states that glycyrrhizinic acid or its salts are added to pharmaceuticals as a flavoring agent or sweetener, but it is difficult to say that glycyrrhizinic acid or its salts have sufficient flavoring properties to improve the feel (flavor) of mouthwash when used.
本発明は、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩、そしてｌ－メントール等を含有するうがい薬において、使用時の泡立ち、結晶析出、そして使用時の液垂れを抑制し、含嗽時の風味にも優れるうがい薬を提供する。 The present invention provides a mouthwash that contains azulene sulfonic acid and/or its salts, cetylpyridinium and/or its salts, l-menthol, etc., which suppresses foaming, crystal precipitation, and dripping during use, and also has an excellent flavor when rinsing.
すなわち本発明は、以下の［１］～［４］を対象とする。
［１］
アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩、及びｌ－メントールを含有する液体組成物において、下記（Ａ）、（Ｂ）、（Ｃ）及び（Ｄ）の各成分が配合されていることを特徴とするうがい薬。
（Ａ）サッカリンナトリウム及びアセスルファムカリウムから選択される１種以上の矯味剤、
（Ｂ）多価アルコール脂肪酸エステル、
（Ｃ）セルロース類、
（Ｄ）ポリオキシエチレン硬化ヒマシ油類。
［２］
前記（Ｂ）多価アルコール脂肪酸エステルが、グリセリン脂肪酸エステルであることを特徴とする、［１］に記載のうがい薬。
［３］
前記（Ｃ）セルロース類が、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース及びヒプロメロースからなる群から選択される１種以上であることを特徴とする、［１］に記載のうがい薬。
［４］
前記（Ｄ）ポリオキシエチレン硬化ヒマシ油類が、ポリオキシエチレン硬化ヒマシ油５、ポリオキシエチレン硬化ヒマシ油１０、ポリオキシエチレン硬化ヒマシ油２０、ポリオキシエチレン硬化ヒマシ油４０、ポリオキシエチレン硬化ヒマシ油５０、ポリオキシエチレン硬化ヒマシ油６０及びポリオキシエチレン硬化ヒマシ油１００からなる群から選択される１種以上であることを特徴とする、［１］乃至［３］のうちいずれか一項に記載のうがい薬。
That is, the present invention relates to the following [1] to [4].
[1]
A mouthwash comprising a liquid composition containing azulene sulfonic acid and/or a salt thereof, cetylpyridinium and/or a salt thereof, and 1-menthol, the mouthwash being characterized in that the following components (A), (B), (C), and (D) are blended therein:
(A) one or more flavoring agents selected from saccharin sodium and acesulfame potassium;
(B) a polyhydric alcohol fatty acid ester,
(C) celluloses,
(D) Polyoxyethylene hydrogenated castor oils.
[2]
The mouthwash according to [1], wherein the (B) polyhydric alcohol fatty acid ester is a glycerin fatty acid ester.
[3]
The mouthwash according to [1], characterized in that the (C) cellulose is one or more selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, and hypromellose.
[4]
The mouthwash according to any one of [1] to [3], characterized in that the polyoxyethylene hydrogenated castor oil (D) is one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene hydrogenated castor oil 100.
本発明によれば、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩及びｌ－メントールを含有するうがい薬（液体組成物）において、うがい薬使用時の泡立ちや液垂れを抑制し、またアズレンスルホン酸及び／又はその塩やｌ－メントールの結晶析出を抑制するとともに、口に含んだ際には苦味等の不快な風味が抑制されてなる、うがい薬を提供することができる。 According to the present invention, it is possible to provide a mouthwash (liquid composition) containing azulene sulfonic acid and/or its salts, cetylpyridinium and/or its salts, and l-menthol, which suppresses foaming and dripping when the mouthwash is used, suppresses crystal precipitation of azulene sulfonic acid and/or its salts and l-menthol, and suppresses unpleasant flavors such as bitterness when held in the mouth.
［うがい薬］
本発明にうがい薬は、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩及びｌ－メントールを含有する液体組成物において、さらに、（Ａ）特定の矯味剤、（Ｂ）多価アルコール脂肪酸エステル、（Ｃ）セルロース類、及び（Ｄ）ポリオキシエチレン硬化ヒマシ油類の各成分が配合されてなることを特徴とする。
[Mouthwash]
The mouthwash of the present invention is characterized in that it is a liquid composition containing azulene sulfonic acid and/or a salt thereof, cetylpyridinium and/or a salt thereof, and 1-menthol, and further contains the following ingredients: (A) a specific flavoring agent, (B) a polyhydric alcohol fatty acid ester, (C) a cellulose, and (D) a polyoxyethylene hydrogenated castor oil.
〈アズレンスルホン酸及び／又はその塩〉
前記アズレンスルホン酸の塩とは、１，４－ジメチル－７－イソプロピルアズレン－３－スルホン酸の薬理学上許容される塩及びその水和物を指す。
前記アズレンスルホン酸及び／又はその塩は、抗炎症作用、抗アレルギー作用、肉芽新生及び上皮形成促進作用を有することが知られている。
薬理学上許容される塩としては、ナトリウム塩、カリウム塩、アンモニウム塩等が挙げることができ、中でもナトリウム塩（通常、アズレンスルホン酸ナトリウムと称する）を挙げることができる。
<Azulene sulfonic acid and/or its salt>
The salt of azulene sulfonic acid refers to a pharmacologically acceptable salt of 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid and a hydrate thereof.
The azulene sulfonic acid and/or its salt are known to have anti-inflammatory and anti-allergic effects, and to promote granulation and epithelial formation.
Examples of pharmacologically acceptable salts include sodium salts, potassium salts, ammonium salts, etc., and among these, sodium salts (usually referred to as sodium azulene sulfonate) are particularly preferred.
〈セチルピリジニウム及び／又はその塩〉
前記セチルピリジニウム及び／又はその塩とは、例えば、セチルピリジニウム塩酸塩が挙げられ、すなわち、１－ヘキサデシルピリジニウムクロリド及びその水和物を挙げることができる。本成分は、殺菌作用を有し、粘膜において細菌の増殖を抑え、のどの炎症を緩和し、歯周病や口臭を予防する効果が知られている。
<Cetylpyridinium and/or its salt>
The cetylpyridinium and/or its salts include, for example, cetylpyridinium hydrochloride, i.e., 1-hexadecylpyridinium chloride and its hydrates. This component has a bactericidal effect, and is known to have the effects of suppressing bacterial growth in mucous membranes, relieving throat inflammation, and preventing periodontal disease and bad breath.
〈ｌ－メントール〉
ｌ－メントールは、前述の通り口中に清涼感を与え、口臭除去の効果を有するとともに、一般に経口薬剤の風味を矯正し摂取しやすくする矯味剤としての役割をも担うものである。
<l-Menthol>
As described above, 1-menthol has the effect of giving a refreshing feeling in the mouth and eliminating bad breath, and also generally plays a role as a flavoring agent that corrects the flavor of oral medications to make them easier to take.
（Ａ）特定の矯味剤
本発明のうがい薬は、（Ａ）矯味剤として、サッカリンナトリウム及びアセスルファム
カリウムから選択される少なくとも一種を含む。
前記サッカリンナトリウム及びアセスルファムカリウムは非糖質性合成甘味料として知られており、本発明のうがい薬では甘味料且つ矯味剤としての役割を担うとともに、後述する（Ｂ）多価アルコール脂肪酸エステルと（Ｃ）セルロース類と組み合わせて使用することで、うがい薬使用時の泡立ちを抑制する役割をも担うことができる。
(A) Specific Flavoring Agent The mouthwash of the present invention contains at least one flavoring agent (A) selected from saccharin sodium and acesulfame potassium.
The above-mentioned saccharin sodium and acesulfame potassium are known as non-carbohydrate synthetic sweeteners, and in the mouthwash of the present invention, they serve as sweeteners and flavoring agents, and when used in combination with (B) polyhydric alcohol fatty acid esters and (C) celluloses described below, they can also serve to suppress foaming when the mouthwash is used.
（Ｂ）多価アルコール脂肪酸エステル、
本発明のうがい薬は（Ｂ）多価アルコール脂肪酸エステルを含む。多価アルコール脂肪酸エステルは、一般に溶解補助剤として使用されることが多いが、本発明のうがい薬においては、うがい薬使用時の泡立ちを抑制する役割をも担うことができる。
前記（Ｂ）多価アルコール脂肪酸エステルの中でも、グリセリン脂肪酸エステルを好ましく用いることができる。
(B) a polyhydric alcohol fatty acid ester,
The mouthwash of the present invention contains (B) a polyhydric alcohol fatty acid ester. Polyhydric alcohol fatty acid esters are generally used as solubilizing agents, but in the mouthwash of the present invention, they can also play a role in suppressing foaming during use of the mouthwash.
Among the (B) polyhydric alcohol fatty acid esters, glycerin fatty acid esters can be preferably used.
（Ｃ）セルロース類
本発明のうがい薬は（Ｃ）セルロース類を含む。セルロース類は、一般に粘稠化剤として粘度の調整（粘度増加）のために添加され得、うがい薬使用時の液垂れを防止する働きを担うとともに、うがい薬使用時の泡立ちを抑制する役割をも担うことができる。
前記（Ｃ）セルロース類の中でも、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース及びヒプロメロース（ヒドロキシプロピルメチルセルロース）からなる群から選択される１種以上を好ましく用いることができる
なお、これらセルロース類は、セルロース中のヒドロキシ基の置換度や粘度等によって種々のグレードが市販されており、うがい薬中の溶解性やうがい薬製品としての粘度を考慮し、種々選択できる。例えばヒプロメロースの場合、メトキシ基の置換度：２２～３０％、ヒドロキシプロポシ基の置換モル数：７～１２％、粘度（２０℃、２質量％水溶液）：３０００～５６００ｍＰａ・ｓであるものを選択することができるが、これに限定されない。
(C) Celluloses The mouthwash of the present invention contains (C) celluloses. Celluloses are generally added as thickeners to adjust the viscosity (increase the viscosity), and can prevent dripping of the mouthwash when it is used, as well as suppress foaming when it is used.
Among the celluloses (C), one or more selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, and hypromellose (hydroxypropyl methylcellulose) can be preferably used. These celluloses are commercially available in various grades depending on the degree of substitution of the hydroxyl group in the cellulose, the viscosity, etc., and can be selected in consideration of the solubility in the mouthwash and the viscosity as a mouthwash product. For example, in the case of hypromellose, one having a degree of substitution of methoxy groups: 22 to 30%, a molar number of substitution of hydroxypropoxy groups: 7 to 12%, and a viscosity (20°C, 2% by weight aqueous solution): 3000 to 5600 mPa·s can be selected, but is not limited thereto.
（Ｄ）ポリオキシエチレン硬化ヒマシ油類
本発明のうがい薬は（Ｄ）ポリオキシエチレン硬化ヒマシ油類を含む。本成分は、ｌ－メントールやアズレンスルホン酸及び／又はその塩などの結晶析出を抑制する、可溶化剤としての働きを担うものである。
前記ポリオキシエチレン硬化ヒマシ油類の中でも、ポリオキシエチレン硬化ヒマシ油５、ポリオキシエチレン硬化ヒマシ油１０、ポリオキシエチレン硬化ヒマシ油２０、ポリオキシエチレン硬化ヒマシ油４０、ポリオキシエチレン硬化ヒマシ油５０、ポリオキシエチレン硬化ヒマシ油６０及びポリオキシエチレン硬化ヒマシ油１００等からなる群から選択される１種以上を好ましく用いることができる。
(D) Polyoxyethylene hydrogenated castor oil The mouthwash of the present invention contains (D) polyoxyethylene hydrogenated castor oil, which acts as a solubilizer to inhibit crystallization of 1-menthol, azulene sulfonic acid and/or its salts, etc.
Among the polyoxyethylene hydrogenated castor oils, one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene hydrogenated castor oil 100 can be preferably used.
〈その他添加剤〉
本発明に係るうがい薬は、本発明の効果並びにうがい薬としての効果（薬効）を損なわない範囲において、前記以外の任意成分としてその他添加剤を配合してもよい。
以下に、その他添加剤として挙げられる代表的な成分を例示するが、これら例示に限定されるものではなく、うがい薬として慣用の各種添加剤を配合することができる。また、これら添加剤の添加的も下記のものに限定されない。
<Other additives>
The mouthwash according to the present invention may contain other additives as optional components other than those described above, provided that the effects of the present invention and the effects (pharmaceutical efficacy) of the mouthwash are not impaired.
Representative examples of other additives are given below, but the present invention is not limited to these examples, and various additives commonly used in mouthwashes can be blended. The addition of these additives is also not limited to the following.
消炎剤として、例えば、グリチルリチン酸二カリウム等を使用することができる。
殺菌剤として、例えば、ベンザルコニウム塩化物、ベンゼトニウム塩化物等を使用することができる。
前記（Ａ）以外の矯味剤として、例えば、カンフル、レモン油、ウイキョウ油、ユーカリ油、ケイヒ油、チョウジ油、バニリン、香料等を使用することができる。
安定化剤として、例えば、アスコルビン酸、ポリビニルアルコール、マクロゴール等を
使用することができる。
アルコール類として、例えば、エタノール、プロピルアルコール等のモノアルコール類、プロピレングリコール、ポリエチレングリコール、糖アルコール（マンニトール等）等の多価アルコール類が挙げられる。
糖アルコール類として、例えば、キシリトール、ソルビトール、グリセリン等を使用することができる。
キレート剤として、例えば、エデト酸ナトリウム、エデト酸カルシウム二ナトリウム、及びそれらの水和物等を使用することができる。
界面活性剤として、例えば、ラウリル硫酸ナトリウム、ショ糖脂肪酸エステル等を使用することができる。
等張化剤として、例えば、塩化ナトリウム、塩化マグネシウム等の無機塩類、プロピレングリコール、Ｄ－マンニトール等の多価アルコール類等を使用することができる。
防腐剤として、例えば、パラベン、チモール、ソルビン酸等を使用することができる。
溶解補助剤として、例えば、トリアセチン、白糖、ベンジルアルコール、ポリビニルピロリドン等を使用することができる。
粘稠（化）剤として、例えば、カルボキシビニルポリマー、カルメロースナトリウム、ゼラチン等を使用することができる。
ｐＨ調節剤として、例えば、クエン酸、乳酸、リン酸、炭酸、及びそれらの塩、それらの塩の水和物等が挙げられる。前記それらの塩、それらの塩の水和物としては、例えば、クエン酸ナトリウム水和物、クエン酸水和物、乳酸ナトリウム、リン酸水素ナトリウム、リン酸水素ナトリウム水和物、炭酸水素ナトリウム等を挙げることができる。
As an anti-inflammatory agent, for example, dipotassium glycyrrhizinate and the like can be used.
As the disinfectant, for example, benzalkonium chloride, benzethonium chloride, etc. can be used.
As flavoring agents other than the above-mentioned (A), for example, camphor, lemon oil, fennel oil, eucalyptus oil, cinnamon oil, clove oil, vanillin, flavors, etc. can be used.
As the stabilizer, for example, ascorbic acid, polyvinyl alcohol, macrogol, etc. can be used.
Examples of the alcohols include monoalcohols such as ethanol and propyl alcohol, and polyhydric alcohols such as propylene glycol, polyethylene glycol, and sugar alcohols (mannitol, etc.).
Examples of sugar alcohols that can be used include xylitol, sorbitol, and glycerin.
As the chelating agent, for example, sodium edetate, calcium disodium edetate, and hydrates thereof can be used.
As the surfactant, for example, sodium lauryl sulfate, sucrose fatty acid ester, etc. can be used.
As the isotonicity agent, for example, inorganic salts such as sodium chloride and magnesium chloride, polyhydric alcohols such as propylene glycol and D-mannitol, etc. can be used.
Preservatives that can be used include, for example, parabens, thymol, sorbic acid, and the like.
As the solubilizing agent, for example, triacetin, sucrose, benzyl alcohol, polyvinylpyrrolidone, etc. can be used.
As a thickening agent, for example, carboxyvinyl polymer, carmellose sodium, gelatin, etc. can be used.
Examples of the pH adjuster include citric acid, lactic acid, phosphoric acid, carbonic acid, salts thereof, and hydrates of the salts thereof. Examples of the salts and hydrates of the salts thereof include sodium citrate hydrate, citric acid hydrate, sodium lactate, sodium hydrogen phosphate, sodium hydrogen phosphate hydrate, and sodium hydrogen carbonate.
本発明のうがい薬において、各成分の配合量は、それら所望の効果を得ることができる配合量範囲であれば特に限定されず、例えば以下の通りとすることができる。なお本濃度は、うがい薬原液としての濃度であり、通常、うがい薬原液を１～３００倍に希釈して使用し、調整濃度によってはそのまま（希釈せずに）使用することもできる。
・アズレンスルホン酸及び／又はその塩：０．００１～０．６ｗ／ｖ％
・セチルピリジニウム及び／又はその塩：０．００１～１０ｗ／ｖ％
・ｌ－メントール：０．００１～１０ｗ／ｖ％
・（Ａ）サッカリンナトリウム及びアセスルファムカリウムから選択される１種以上の矯味剤：０．０５～２０ｗ／ｖ％
・（Ｂ）多価アルコール脂肪酸エステル：０．００１～５ｗ／ｖ％
・（Ｃ）セルロース類：０．００１～５ｗ／ｖ％
・（Ｄ）ポリオキシエチレン硬化ヒマシ油類：０．００１～５ｗ／ｖ％
In the mouthwash of the present invention, the blending amount of each component is not particularly limited as long as it is within the blending amount range that can obtain the desired effect, and can be, for example, as follows. Note that the above concentrations are the concentrations of the mouthwash stock solution, which is usually diluted 1 to 300 times before use, and depending on the adjusted concentration, it can also be used as is (without dilution).
Azulene sulfonic acid and/or its salt: 0.001 to 0.6 w/v%
Cetylpyridinium and/or its salts: 0.001 to 10 w/v%
l-Menthol: 0.001 to 10 w/v%
(A) One or more flavoring agents selected from saccharin sodium and acesulfame potassium: 0.05 to 20 w/v%
(B) Polyhydric alcohol fatty acid ester: 0.001 to 5 w/v%
(C) Cellulose: 0.001 to 5 w/v%
(D) Polyoxyethylene hydrogenated castor oils: 0.001 to 5 w/v%
本発明のうがい薬は、ポリエチレン（ＰＥ）、ポリプロピレン（ＰＰ）、ポリエチレンテレフタレート（ＰＥＴ）等の慣用の樹脂製容器や、ガラス製容器にて保存できる。また、容器の形状は特に限定されない。 The mouthwash of the present invention can be stored in a conventional resin container such as polyethylene (PE), polypropylene (PP), or polyethylene terephthalate (PET), or in a glass container. There are no particular limitations on the shape of the container.
［うがい薬の製造方法］
本発明のうがい薬の製造方法の一例を以下に挙げるが、本法に特に限定されることなく製造可能である。
例えば、セチルピリジニウム及び／又はその塩、ｌ－メントール、（Ｂ）多価アルコール脂肪酸エステル及び（Ｄ）ポリオキシエチレン硬化ヒマシ油類を混合してセチルピリジニウム相とする。セチルピリジニウム相調製時、必要により加熱を行ってもよいし、またアルコール類を添加するなどして溶解性を高めてもよい。なお調製時に系内に水が存在するとセチルピリジニウム相が泡立ち易くなり、泡立ちが収まるまで時間を要する場合がある。
セチルピリジニウム相とは別に、（Ａ）特定の矯味剤と（Ｃ）セルロース類、必要に応じて水を添加し、矯味剤相とする。
前記セチルピリジニウム相と矯味剤相を合わせて均一な相とした後、ここにアズレンスルホン酸及び／又はその塩、あるいは必要に応じてその水溶液を加えて溶解する。また前述の〈その他添加剤〉は、セチルピリジニウム相又は矯味剤相の調製時に添加してもよいし、これらを合わせて均一な相とする際、アズレンスルホン酸類を加える前又は後に、適時加えることができる。なおアズレンスルホン酸類を、各成分の溶解を確認した後に投入することで、各成分・添加剤の未溶解物や析出物を容易に確認できる。
またアズレンスルホン酸類を投入時、系内のｐＨを弱酸性（ｐＨ６．５～８．５）に維持することでアズレンスルホン酸類の安定性高めることができる（含量低下を抑制する）ことが期待できるため、必要に応じて系内のｐＨを調整することができる。
その後、必要により水を添加して容量補正し、うがい薬（原液）を得ることができる。
[Manufacturing method of mouthwash]
An example of a method for producing the mouthwash of the present invention will be described below, but the method is not particularly limited to this method.
For example, cetylpyridinium and/or its salt, 1-menthol, (B) polyhydric alcohol fatty acid ester, and (D) polyoxyethylene hydrogenated castor oil are mixed to prepare the cetylpyridinium phase. When preparing the cetylpyridinium phase, heating may be performed as necessary, or alcohols may be added to increase the solubility. If water is present in the system during preparation, the cetylpyridinium phase tends to foam, and it may take time for the foaming to subside.
Separately from the cetylpyridinium phase, (A) a specific flavoring agent and (C) a cellulose compound are added, and water is added as necessary to form a flavoring agent phase.
After the cetylpyridinium phase and the flavoring agent phase are mixed to form a homogeneous phase, azulene sulfonic acid and/or its salt, or its aqueous solution as necessary, are added and dissolved therein.The above-mentioned <other additives> may be added when preparing the cetylpyridinium phase or the flavoring agent phase, or when combining them to form a homogeneous phase, they can be added before or after adding azulene sulfonic acids as appropriate.In addition, by adding azulene sulfonic acids after confirming the dissolution of each component, it is easy to confirm the undissolved matter or precipitate of each component or additive.
In addition, when adding azulene sulfonic acids, it is expected that the stability of the azulene sulfonic acids can be increased (a decrease in content can be suppressed) by maintaining the pH of the system at a weak acidic level (pH 6.5 to 8.5), and therefore the pH of the system can be adjusted as necessary.
Thereafter, water is added to adjust the volume as necessary to obtain a mouthwash (undiluted solution).
以下、本発明を実施例により、さらに詳しく説明する。ただし、本発明はこれら実施例に限定されるものではない。 The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to these examples.
［うがい薬原液及びうがい薬の調製（１）］
〈実施例１〉
ポリオキシエチレン硬化ヒマシ油６０ ０．１ｇを加熱して溶解後、プロピレングリコール ５５ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル
０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール ５ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム ２．５ｇ及びヒドロキシエチルセルロースＳＥ－６００ ０．１ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇを加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例１のうがい薬原液を得た（表１）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例１のうがい薬を得た（表２）。
〈実施例２〉
実施例１のサッカリンナトリウムを、アセスルファムカリウムに変えたほかは実施例１と同様にして、実施例２のうがい薬原液及びうがい薬を得た。
[Preparation of mouthwash stock solution and mouthwash (1)]
Example 1
0.1 g of polyoxyethylene hydrogenated castor oil 60 was dissolved by heating, and then dissolved in 55 g of propylene glycol. 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 5 g of 1-menthol were added thereto, and dissolved by stirring at room temperature to obtain a cetylpyridinium phase.
Next, 2.5 g of sodium saccharin and 0.1 g of hydroxyethyl cellulose SE-600 were added to 30 g of purified water and dissolved by stirring at room temperature to obtain a flavoring agent phase.
The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate was added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate of Example 1 (Table 1).
0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 1 (Table 2).
Example 2
A mouthwash concentrate and a mouthwash of Example 2 were obtained in the same manner as in Example 1, except that the saccharin sodium in Example 1 was replaced with acesulfame potassium.
〈比較例１〉
実施例１のサッカリンナトリウムを、グリチルリチン酸二カリウムに変えたほかは実施例１と同様にして、比較例１のうがい薬原液及びうがい薬を得た。
〈比較例２〉
実施例１のサッカリンナトリウムを配合しなかったほかは実施例１と同様にして、比較例２のうがい薬原液及びうがい薬を得た。
〈比較例３〉
実施例１のヒドロキシエチルセルロースＳＥ－６００を配合しなかったほかは実施例１と同様にして、比較例３のうがい薬原液及びうがい薬を得た。
〈比較例４〉
実施例１のグリセリン脂肪酸エステルを配合しなかったほかは実施例１と同様にして、比較例４のうがい薬原液及びうがい薬を得た。
〈比較例５〉
実施例１のヒドロキシエチルセルロースＳＥ－６００及びグリセリン脂肪酸エステルを配合しなかったほかは実施例１と同様にして、比較例５のうがい薬原液及びうがい薬を得た。
〈比較例６〉
実施例１のポリオキシエチレン硬化ヒマシ油６０を配合しなかったほかは実施例１と同
様にして、比較例６のうがい薬原液及びうがい薬を得た。
〈比較例７〉
実施例１のサッカリンナトリウム、ヒドロキシエチルセルロースＳＥ－６００、グリセリン脂肪酸エステル及びポリオキシエチレン硬化ヒマシ油６０を配合しなかったほかは実施例１と同様にして、比較例７のうがい薬原液及びうがい薬を得た。
Comparative Example 1
A mouthwash concentrate and mouthwash of Comparative Example 1 were obtained in the same manner as in Example 1, except that the sodium saccharin in Example 1 was replaced with dipotassium glycyrrhizinate.
Comparative Example 2
A mouthwash concentrate and mouthwash of Comparative Example 2 were obtained in the same manner as in Example 1, except that the saccharin sodium of Example 1 was not added.
Comparative Example 3
A mouthwash concentrate and a mouthwash of Comparative Example 3 were obtained in the same manner as in Example 1, except that the hydroxyethyl cellulose SE-600 of Example 1 was not added.
Comparative Example 4
A mouthwash concentrate and a mouthwash of Comparative Example 4 were obtained in the same manner as in Example 1, except that the glycerin fatty acid ester of Example 1 was not added.
Comparative Example 5
A mouthwash concentrate and a mouthwash of Comparative Example 5 were obtained in the same manner as in Example 1, except that the hydroxyethyl cellulose SE-600 and the glycerin fatty acid ester of Example 1 were not blended.
Comparative Example 6
A mouthwash concentrate and a mouthwash of Comparative Example 6 were obtained in the same manner as in Example 1, except that the polyoxyethylene hydrogenated castor oil 60 of Example 1 was not blended.
Comparative Example 7
A mouthwash concentrate and mouthwash of Comparative Example 7 were obtained in the same manner as in Example 1, except that the saccharin sodium, hydroxyethyl cellulose SE-600, glycerin fatty acid ester, and polyoxyethylene hydrogenated castor oil 60 of Example 1 were not added.
実施例１～２及び比較例１～７で調製したうがい薬原液の処方を表１に、またうがい薬（希釈後）の処方を表２に、夫々示す。 The formulations of the mouthwash concentrates prepared in Examples 1 and 2 and Comparative Examples 1 to 7 are shown in Table 1, and the formulations of the mouthwashes (after dilution) are shown in Table 2.
［試験例１：使用感（矯味）］
実施例１～２及び比較例１～７のうがい薬を、適量口に含み、下記基準により官能評価を行った。
＜使用感（矯味） 評価基準＞
〇：苦味を感じにくく、うがいしやすい（矯味を感じる）
△：苦味が僅かにあり、うがいがしにくい（わずかに矯味を感じる）
×：苦味があり、うがいに困難を感じる（矯味を感じない）
[Test Example 1: Usability (flavoring)]
An appropriate amount of each of the mouthwashes of Examples 1 and 2 and Comparative Examples 1 to 7 was placed in the mouth, and a sensory evaluation was carried out according to the following criteria.
<Usability (flavor correction) evaluation criteria>
〇: Less bitter and easier to gargle (taste is corrected)
△: Slightly bitter, difficult to gargle (slightly flavored)
×: Bitter taste, difficult to gargle (no taste detected)
［試験例２：泡立ち抑制評価］
ＪＩＳの泡立ち試験を参照（ＪＩＳ Ｋ３３６２－２００８ ８．５起泡力及び泡の安定度、ロス・マイルス法参照）し、以下の手順にて実施例１～２及び比較例１～７のうがい薬の泡立ち試験を行った。
５０ｍＬビュレットに各うがい薬（検体）約５０ｍＬを入れ、更に、１００ｍＬメスシリンダーに前記検体約２０ｍＬを加え、ビュレットの先端（コック側）からメスシリンダー中の検液の液面まで約４５ｃｍとなるようにビュレットを設置した。
ビュレットのコックを全開にし、全量をメスシリンダーに加え、直ちに生じた泡の高さを測定し、下記基準により泡立ち抑制について評価した。
＜泡立ち抑制 評価基準＞
〇：０～２０ｃｍ
△：２１～４０ｃｍ
×：４１ｃｍ以上
[Test Example 2: Evaluation of foam suppression]
Referring to the JIS foaming test (JIS K3362-2008 8.5 Foaming power and foam stability, Ross-Miles method), the mouthwashes of Examples 1 and 2 and Comparative Examples 1 to 7 were subjected to a foaming test according to the following procedure.
Approximately 50 mL of each mouthwash (specimen) was placed in a 50 mL burette, and approximately 20 mL of the specimen was added to a 100 mL measuring cylinder. The burette was placed so that the tip (cock side) of the burette was approximately 45 cm from the liquid level of the test liquid in the measuring cylinder.
The cock of the burette was fully opened and the entire amount was added to a measuring cylinder. The height of the foam that immediately formed was measured and the foaming inhibition was evaluated according to the following criteria.
<Foam suppression evaluation criteria>
○: 0 to 20 cm
△: 21-40cm
×: 41 cm or more
［試験例３：液垂れ抑制評価］
一般にうがい薬は、うがい薬（原液）の入った容器から付属するカップやコップ等に適量を量り取り、これを水で希釈して使用（含嗽）する。以下の手順にて、うがい薬（原液）をコップ等にとる際の液垂れ性を評価した。
プラスチック容器（市販のうがい薬容器）に実施例１～２及び比較例１～７のうがい薬原液を適量充填した。うがい薬使用時と同様に、付属コップに約０．４ｍＬのうがい薬原液を量り取る時の液垂れ抑制について下記基準により評価した。
＜液垂れ抑制 評価基準＞
〇：液垂れせずに量り取れる
×：液垂れし、使用しにくい
[Test Example 3: Evaluation of Dripping Suppression]
Generally, mouthwash is used by measuring an appropriate amount from a container containing the mouthwash (undiluted) into an attached cup or glass, diluting it with water, and rinsing it. The dripping property of the mouthwash (undiluted) when pouring it into a glass or glass was evaluated using the following procedure.
A plastic container (a commercially available mouthwash container) was filled with an appropriate amount of the mouthwash concentrate of Examples 1 and 2 and Comparative Examples 1 to 7. As in the case of using the mouthwash, the suppression of dripping when measuring out about 0.4 mL of the mouthwash concentrate into the attached cup was evaluated according to the following criteria.
<Drip suppression evaluation criteria>
〇: The liquid can be measured without dripping. ×: The liquid drips and is difficult to use.
［試験例４：結晶析出抑制評価］
実施例１～２及び比較例１～７のうがい薬を、一夜室温で放置し、目視にて結晶析出の有無を確認し、結晶析出の抑制について下記基準により評価した。
＜結晶析出抑制 評価基準＞
〇：結晶析出しない
×：結晶析出する
[Test Example 4: Evaluation of Crystal Precipitation Inhibition]
The mouthwashes of Examples 1 and 2 and Comparative Examples 1 to 7 were left at room temperature overnight, and the presence or absence of crystal precipitation was confirmed by visual inspection, and the inhibition of crystal precipitation was evaluated according to the following criteria.
<Crystallization Suppression Evaluation Criteria>
◯: No crystallization occurs ×: Crystallization occurs
表２に示すように、（Ａ）矯味剤としてサッカリンナトリウム（実施例１）及びアセスルファムカリウム（実施例２）を配合したうがい薬は、使用感（うがいのしやすさ（矯味（苦味の抑制など））に優れ、泡立ち抑制、液垂れ抑制及び結晶析出抑制をしていたが、従来矯味剤としても配合されているグリチルリチン酸二カリウム（比較例１）を配合したうがい薬は、使用感が悪いとする結果となった。
（Ａ）矯味剤（サッカリンナトリウム、アセスルファムカリウム）を配合しないうがい薬（比較例２）は、使用感が著しく悪く、しかも後述する（Ｃ）セルロース類や、泡立ち抑制への寄与が期待できる界面活性剤とされる（Ｂ）多価アルコール脂肪酸エステルを配合していても、泡立ち抑制に至らなかった。（Ｃ）セルロース類（ヒドロキシエチルセルロース）を配合しないうがい薬（比較例３）は、液垂れが著しく生じ、また泡立ち抑制効果も低いとする結果となった。（Ｂ）多価アルコール脂肪酸エステル（グリセリン脂肪酸エステル）を配合しないうがい薬（比較例４）は、泡立ち抑制効果が低いとする結果となった。更に、（Ｃ）セルロース類（ヒドロキシエチルセルロース）及び（Ｂ）多価アルコール脂肪酸エステル（グリセリン脂肪酸エステル）を配合しないうがい薬（比較例５）も
、泡立ち抑制効果が低い結果となった。
一方、結晶析出抑制に寄与する（Ｄ）ポリオキシエチレン硬化ヒマシ油類を配合しないうがい薬（比較例６）は、結晶析出抑制効果が低かった。
また、（Ａ）矯味剤（サッカリンナトリウム、アセスルファムカリウム）、（Ｂ）多価アルコール脂肪酸エステル（グリセリン脂肪酸エステル）、（Ｃ）セルロース類（ヒドロキシエチルセルロース）及び（Ｄ）ポリオキシエチレン硬化ヒマシ油類をいずれも非配合としたうがい薬（比較例７）は、使用感が悪く、泡立ち、液垂れ及び結晶析出抑制効果が低かった。
なお本処方では、糖類の泡立ち抑制効果及びｌ－メントールの結晶析出抑制効果を明確とするため、一般的な処方と比べて糖類並びにｌ－メントールを多めに配合しており、またそのため、この一連の試験に係る評価基準は、後述する同様の試験における評価基準とは異なることがある。
As shown in Table 2, (A) the mouthwashes containing saccharin sodium (Example 1) and acesulfame potassium (Example 2) as flavoring agents were excellent in usability (ease of gargling (flavoring (suppression of bitterness, etc.)) and suppressed foaming, dripping, and crystal precipitation, but the mouthwashes containing dipotassium glycyrrhizinate (Comparative Example 1), which has also been used as a flavoring agent in the past, were found to have a poor usability.
The mouthwash (Comparative Example 2) not containing (A) flavoring agents (saccharin sodium, acesulfame potassium) had a very poor feel when used, and did not suppress foaming even when it contained (C) celluloses, which will be described later, and (B) polyhydric alcohol fatty acid esters, which are surfactants that can be expected to contribute to foaming suppression. The mouthwash (Comparative Example 3) not containing (C) celluloses (hydroxyethyl cellulose) caused significant dripping and had a low foaming suppression effect. The mouthwash (Comparative Example 4) not containing (B) polyhydric alcohol fatty acid esters (glycerin fatty acid esters) had a low foaming suppression effect. Furthermore, the mouthwash (Comparative Example 5) not containing (C) celluloses (hydroxyethyl cellulose) and (B) polyhydric alcohol fatty acid esters (glycerin fatty acid esters) also had a low foaming suppression effect.
On the other hand, the mouthwash (Comparative Example 6) not containing the polyoxyethylene hydrogenated castor oil (D) which contributes to the inhibition of crystal precipitation had a low inhibitory effect on crystal precipitation.
In addition, a mouthwash (Comparative Example 7) that did not contain any of (A) flavoring agents (saccharin sodium, acesulfame potassium), (B) polyhydric alcohol fatty acid esters (glycerin fatty acid esters), (C) celluloses (hydroxyethyl cellulose), and (D) polyoxyethylene hydrogenated castor oils had a poor feel when used and was poor in foaming, dripping, and crystal precipitation inhibitory effects.
In addition, in this formulation, in order to clarify the foaming-inhibiting effect of sugar and the crystal precipitation-inhibiting effect of l-menthol, a larger amount of sugar and l-menthol are blended compared to general formulations, and therefore, the evaluation criteria for this series of tests may differ from the evaluation criteria for similar tests described below.
［うがい薬原液及びうがい薬の調製（２）］
〈実施例３〉
ポリオキシエチレン硬化ヒマシ油６０ ０．１ｇを加熱して溶解後、プロピレングリコール ５０ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル
０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール １ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム １ｇ及びヒプロメロース６０ＳＨ－４０００ ０．１ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇ及び適量のｐＨ調節剤を加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例３のうがい薬原液（ｐＨ７．５）を得た（表３）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例３のうがい薬を得た（表４）。
〈実施例４〉
実施例３のヒプロメロース６０ＳＨ－４０００の配合量を０．１２ｇに変えたほかは実施例３と同様にして、実施例４のうがい薬原液及びうがい薬を得た。
〈実施例５〉
実施例３のヒプロメロース６０ＳＨ－４０００をヒプロメロース９０ＳＨ－４０００ＳＲに変え、配合量を０．１５ｇに変えたほかは実施例３と同様にして、実施例５のうがい薬原液及びうがい薬を得た。
〈実施例６〉
実施例３のヒプロメロース６０ＳＨ－４０００をヒドロキシエチルセルロースＳＥ－９００に変えたほかは実施例３と同様にして、実施例６のうがい薬原液及びうがい薬を得た。
[Preparation of mouthwash stock solution and mouthwash (2)]
Example 3
0.1 g of polyoxyethylene hydrogenated castor oil 60 was dissolved by heating, and then dissolved in 50 g of propylene glycol. 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of 1-menthol were added thereto, and dissolved by stirring at room temperature to obtain a cetylpyridinium phase.
Next, 1 g of sodium saccharin and 0.1 g of hypromellose 60SH-4000 were added to 30 g of purified water and dissolved by stirring at room temperature to obtain a flavoring agent phase.
The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate and an appropriate amount of pH adjuster were added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate of Example 3 (pH 7.5) (Table 3).
0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 3 (Table 4).
Example 4
A mouthwash concentrate and a mouthwash of Example 4 were obtained in the same manner as in Example 3, except that the amount of hypromellose 60SH-4000 in Example 3 was changed to 0.12 g.
Example 5
A mouthwash concentrate and mouthwash of Example 5 were obtained in the same manner as in Example 3, except that the hypromellose 60SH-4000 in Example 3 was changed to hypromellose 90SH-4000SR and the blended amount was changed to 0.15 g.
Example 6
A mouthwash concentrate and a mouthwash of Example 6 were obtained in the same manner as in Example 3, except that hypromellose 60SH-4000 in Example 3 was replaced with hydroxyethyl cellulose SE-900.
〈比較例８〉
実施例３のヒプロメロース６０ＳＨ－４０００を配合しないほかは実施例３と同様にして、比較例８のうがい薬原液及びうがい薬を得た。
Comparative Example 8
A mouthwash concentrate and a mouthwash of Comparative Example 8 were obtained in the same manner as in Example 3, except that hypromellose 60SH-4000 of Example 3 was not added.
実施例３～６及び比較例８で調製したうがい薬原液の処方を表３に、またうがい薬（希釈後）の処方を表４に、夫々示す。 The formulations of the mouthwash concentrates prepared in Examples 3 to 6 and Comparative Example 8 are shown in Table 3, and the formulations of the mouthwashes (after dilution) are shown in Table 4.
［試験例５：粘度評価］
実施例３～６及び比較例８のうがい薬原液１００ｍＬが入った１００ｍＬのビーカーを用意し、室温（２０±５℃）下、回転粘度計（ＶＩＳＣＯＭＥＴＥＲ ＴＶ－１０、東機産業（株））を用いて試験を行った。ローターはＭ－１ローターを用い、回転速度１００ｒｐｍで１２０秒間測定を行った。
なお、粘度が１０ｍＰａ・ｓ以下であると、うがい薬原液として粘度が低く、これを量り取る際に液垂れを生じやすくなるとが懸念される。
[Test Example 5: Viscosity Evaluation]
A 100 mL beaker containing 100 mL of the mouthwash concentrate of Examples 3 to 6 and Comparative Example 8 was prepared, and a test was performed using a rotational viscometer (VISCOMETER TV-10, Toki Sangyo Co., Ltd.) at room temperature (20±5°C). The rotor used was an M-1 rotor, and measurements were performed for 120 seconds at a rotation speed of 100 rpm.
If the viscosity is less than 10 mPa·s, the viscosity will be low as a mouthwash concentrate, and there is a concern that the liquid may drip when measured out.
また、実施例３～６及び比較例８のうがい薬原液について、前述の［試験例３：液垂れ抑制評価］の手順に従い、うがい薬原液を量り取る時の液垂れ抑制について評価した。
これらの結果をあわせて表４に示す。
In addition, for the mouthwash concentrates of Examples 3 to 6 and Comparative Example 8, the suppression of dripping when the mouthwash concentrate was measured out was evaluated according to the procedure of [Test Example 3: Evaluation of Dripping Suppression] described above.
These results are shown together in Table 4.
本処方では、粘稠化剤であるヒドロキシエチルセルロースＳＥ－９００、ヒプロメロース６０ＳＨ－４０００及びヒプロメロース９０ＳＨ－４０００ＳＲの配合量を変えた製剤の粘度と液垂れ抑制効果を評価した。
粘稠化剤を配合していない比較例８では、うがい薬原液の粘度が１０ｍＰａ・ｓ以下となり、また原液を量り取る際に液垂れし、使用しにくいとする結果となった。それに対して、粘稠化剤を０．１０％～０．１５％配合した実施例３～６のうがい薬原液では、使用した粘稠化剤の種類やグレードによらず粘度が１５ｍＰａ・ｓ以上となり、液垂れせずに量り取れた。
In this formulation, the viscosity and dripping suppression effect of the formulations containing different amounts of the thickening agents hydroxyethylcellulose SE-900, hypromellose 60SH-4000 and hypromellose 90SH-4000SR were evaluated.
In Comparative Example 8, which did not contain a thickener, the viscosity of the mouthwash concentrate was 10 mPa·s or less, and the concentrate dripped when measured out, making it difficult to use. In contrast, the mouthwash concentrates of Examples 3 to 6, which contained 0.10% to 0.15% thickener, had a viscosity of 15 mPa·s or more regardless of the type and grade of the thickener used, and could be measured out without dripping.
［うがい薬原液及びうがい薬の調製（３）］
〈実施例７〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０） ０．５ｇを加熱して溶解後、プロピレングリコール ５５ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル ０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール １ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム １ｇ及びヒプロメロース（メトロー
ズ９０ＳＨ－４０００ＳＲ） ０．５ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇを加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例７のうがい薬原液を得た（表５）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例７のうがい薬を得た（表６）。
〈実施例８〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレン硬化ヒマシ油５０（ニッコールＨＣＯ－５０）に変えたほかは、実施例７と同様にして実施例８のうがい薬原液及びうがい薬を得た。
〈実施例９〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレン硬化ヒマシ油６０（ニッコールＨＣＯ－６０）に変えたほかは、実施例７と同様にして実施例９のうがい薬原液及びうがい薬を得た。
〈実施例１０〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレン硬化ヒマシ油１００（ニッコールＨＣＯ－１００）に変えたほかは、実施例７と同様にして実施例１０のうがい薬原液及びうがい薬を得た。
[Preparation of mouthwash stock solution and mouthwash (3)]
Example 7
0.5 g of polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was dissolved by heating, and then dissolved in 55 g of propylene glycol. 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of 1-menthol were added thereto, and the mixture was stirred at room temperature to dissolve, forming a cetylpyridinium phase.
Next, 1 g of sodium saccharin and 0.5 g of hypromellose (Metolose 90SH-4000SR) were added to 30 g of purified water and dissolved by stirring at room temperature to obtain a flavoring agent phase.
The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate was added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate of Example 7 (Table 5).
0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 7 (Table 6).
Example 8
A mouthwash concentrate and a mouthwash of Example 8 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene hydrogenated castor oil 50 (Nikkol HCO-50).
Example 9
A mouthwash concentrate and a mouthwash of Example 9 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene hydrogenated castor oil 60 (Nikkol HCO-60).
Example 10
A mouthwash concentrate and a mouthwash of Example 10 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene hydrogenated castor oil 100 (Nikkol HCO-100).
〈比較例９〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリラウリン酸デカグリセリル（ニッコールＤｅｃａｇｌｙｎ １－Ｌ）に変えたほかは、実施例７と同様にして比較例Ａのうがい薬原液を得た（表Ａ）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、比較例Ａのうがい薬を得た（表Ｂ）。
〈比較例１０〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート２０（ニッコールＴＬ－１０）に変えたほかは、実施例７と同様にして比較例１０のうがい薬原液及びうがい薬を得た。
〈比較例１１〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート４０（ニッコールＴＰ－１０ＥＸ）に変えたほかは、実施例７と同様にして比較例１１のうがい薬原液及びうがい薬を得た。
〈比較例１２〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート６０（ニッコールＴＳ－１０ＭＶ）に変えたほかは、実施例７と同様にして比較例１２のうがい薬原液及びうがい薬を得た。
〈比較例１３〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリソルベート８０（ニッコールＴＯ－１０ＭＶ）に変えたほかは、実施例７と同様にして比較例１３のうがい薬原液及びうがい薬を得た。
〈比較例１４〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ラウロマクロゴール（ニッコールＢＬ－２１）に変えたほかは、実施例７と同様にして比較例１４のうがい薬原液及びうがい薬を得た。
〈比較例１５〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ラウロマクロゴール（ニッコールＢＬ－２５）に変えたほかは、実施例７と同様にして比較例１５のうがい薬原液及びうがい薬を得た。
〈比較例１６〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレンオレイルエーテル（ニッコールＢＯ－２０Ｖ）に変えたほかは、実施例７と同様にして比較例１６のうがい薬原液及びうがい薬を得た。
〈比較例１７〉
ポリオキシエチレン硬化ヒマシ油４０（ニッコールＨＣＯ－４０）を、ポリオキシエチレンオレイルエーテル（ニッコールＢＯ－５０Ｖ）に変えたほかは、実施例７と同様にして比較例１７のうがい薬原液及びうがい薬を得た。
Comparative Example 9
A mouthwash concentrate of Comparative Example A was obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was replaced with polydecaglyceryl laurate (Nikkol Decaglyn 1-L) (Table A).
0.4 mL of the mouthwash stock solution was diluted with 100 mL of water to obtain the mouthwash of Comparative Example A (Table B).
Comparative Example 10
A mouthwash concentrate and a mouthwash of Comparative Example 10 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was replaced with polysorbate 20 (Nikkol TL-10).
Comparative Example 11
A mouthwash concentrate and a mouthwash of Comparative Example 11 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was replaced with polysorbate 40 (Nikkol TP-10EX).
Comparative Example 12
A mouthwash concentrate and a mouthwash of Comparative Example 12 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was replaced with polysorbate 60 (Nikkol TS-10MV).
Comparative Example 13
A mouthwash concentrate and a mouthwash of Comparative Example 13 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polysorbate 80 (Nikkol TO-10MV).
Comparative Example 14
A mouthwash concentrate and a mouthwash of Comparative Example 14 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to lauromacrogol (Nikkol BL-21).
Comparative Example 15
A mouthwash concentrate and a mouthwash of Comparative Example 15 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to lauromacrogol (Nikkol BL-25).
Comparative Example 16
A mouthwash concentrate and a mouthwash of Comparative Example 16 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene oleyl ether (Nikkol BO-20V).
Comparative Example 17
A mouthwash concentrate and a mouthwash of Comparative Example 17 were obtained in the same manner as in Example 7, except that polyoxyethylene hydrogenated castor oil 40 (Nikkol HCO-40) was changed to polyoxyethylene oleyl ether (Nikkol BO-50V).
実施例７～１０及び比較例９～１７で調製したうがい薬原液の処方を表５に、またうがい薬（希釈後）の処方を表６に、夫々示す。 The formulations of the mouthwash concentrates prepared in Examples 7 to 10 and Comparative Examples 9 to 17 are shown in Table 5, and the formulations of the mouthwashes (after dilution) are shown in Table 6.
［試験例６：アズレンスルホン酸ナトリウム添加前のうがい薬原液の外観評価］
アズレンスルホン酸ナトリウムを添加すると濃紺色となり、うがい薬原液の外観（濁り等）が評価できないため、アズレンスルホン酸ナトリウム添加前にうがい薬原液の外観を
評価した。
実施例７～１０及び比較例９～１７のうがい薬原液の外観を、アズレンスルホン酸ナトリウム添加前に、下記基準により目視にて評価を行った。得られた結果を表７に示す。
＜アズレンスルホン酸ナトリウム添加前のうがい薬原液の外観 評価基準＞
〇：澄明である
△：わずかに濁りがある
×：濁りがある
[Test Example 6: Appearance evaluation of mouthwash concentrate before addition of sodium azulene sulfonate]
When sodium azulene sulfonate was added, the color turned dark blue, making it impossible to evaluate the appearance (turbidity, etc.) of the mouthwash concentrate, so the appearance of the mouthwash concentrate was evaluated before adding sodium azulene sulfonate.
The appearance of the mouthwash concentrates of Examples 7 to 10 and Comparative Examples 9 to 17 was visually evaluated according to the following criteria before the addition of sodium azulene sulfonate. The results are shown in Table 7.
<Appearance of mouthwash concentrate before adding sodium azulene sulfonate Evaluation criteria>
◯: Clear △: Slightly cloudy ×: Cloudy
［試験例７：うがい薬（希釈後）の使用感（甘味）］
実施例７～１０及び比較例９～１７のうがい薬（希釈後）を適量口に含み、使用感（甘味）を、官能試験で下記基準により評価を行った。得られた結果を表７に示す。
＜うがい薬（希釈後）の使用感（甘味） 評価基準＞
〇：甘味があり、うがいしやすい
△：やや甘味があるが、うがいしにくい
×：甘味がなく、うがいに困難を感じる
[Test Example 7: Sensation of mouthwash (after dilution) (sweetness)]
An appropriate amount of each of the mouthwashes (diluted) of Examples 7 to 10 and Comparative Examples 9 to 17 was placed in the mouth, and the sensation of use (sweetness) was evaluated in a sensory test according to the following criteria. The results are shown in Table 7.
<Evaluation criteria for sweetness of diluted mouthwash>
〇: Sweet, easy to gargle △: Slightly sweet, but difficult to gargle ×: No sweetness, difficult to gargle
［試験例８：うがい薬原液の滴下（希釈操作時）における結晶析出評価］
５０ｍＬビーカーに水道水５０ｍＬを入れ、そこに実施例７～１０及び比較例９～１７のうがい薬原液を適量滴下した。滴下して５分間放置後、結晶析出の有無を目視にて確認し、下記基準により評価した。得られた結果を表７に示す。
＜うがい薬原液の滴下（希釈操作時）の結晶析出 評価基準＞
〇：結晶析出しない
×：結晶析出した
[Test Example 8: Evaluation of crystal precipitation when dripping mouthwash concentrate (during dilution operation)]
50 mL of tap water was placed in a 50 mL beaker, and an appropriate amount of the mouthwash concentrate of Examples 7 to 10 and Comparative Examples 9 to 17 was dropped into it. After leaving it for 5 minutes, the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria. The obtained results are shown in Table 7.
<Evaluation criteria for crystal precipitation when dripping undiluted mouthwash solution (during dilution)>
◯: No crystallization occurred ×: Crystallization occurred
［試験例９：うがい薬（希釈後）の液の濁度評価］
実施例７～１０及び比較例９～１７のうがい薬を調製後、紫外可視分光光度計（ＵＶ－１６００、（株）島津製作所）を用いて、波長６６０ｎｍの濁度（ＯＤ６６０）を測定し、下記評価基準にて評価した。得られた結果を表７に示す。なお濁りが生じると結晶析出しやすいため、濁度測定は結晶析出の一つの指標といえる。
＜うがい薬（希釈後）の液の濁度（濁度：ＯＤ６６０） 評価基準＞
〇：０．０３５以下
△：０．０３５～０．０４４
×：０．０４５以上
[Test Example 9: Evaluation of turbidity of mouthwash (after dilution)]
After preparing the mouthwashes of Examples 7 to 10 and Comparative Examples 9 to 17, the turbidity (OD 660 ) at a wavelength of 660 nm was measured using an ultraviolet-visible spectrophotometer (UV-1600, Shimadzu Corporation) and evaluated according to the following evaluation criteria. The results are shown in Table 7. Note that since the occurrence of turbidity makes crystals more likely to precipitate, the turbidity measurement can be considered as one index of crystal precipitation.
<Evaluation criteria for turbidity (turbidity: OD 660 ) of mouthwash (after dilution)>
◯: 0.035 or less △: 0.035 to 0.044
×: 0.045 or more
［試験例１０：うがい薬（希釈後）の低温下における結晶析出評価］
実施例７～１０及び比較例９～１７のうがい薬を、一夜５℃で保存し、目視にて結晶析出の有無を確認し、結晶析出の抑制について下記基準により評価した。得られた結果を表７に示す。
＜うがい薬（希釈後）低温（５℃）下の結晶析出 評価基準＞
〇：結晶析出せず、液が澄明である。
△：結晶析出しないが、液が濁る。
×：結晶析出する。
[Test Example 10: Evaluation of crystal precipitation of mouthwash (after dilution) at low temperature]
The mouthwashes of Examples 7 to 10 and Comparative Examples 9 to 17 were stored overnight at 5° C., and the presence or absence of crystal precipitation was visually confirmed, and the inhibition of crystal precipitation was evaluated according to the following criteria. The obtained results are shown in Table 7.
<Crystallization of mouthwash (after dilution) at low temperature (5°C) - Evaluation criteria>
◯: No crystals were precipitated and the liquid was clear.
Δ: No crystallization occurs, but the solution becomes cloudy.
×: Crystals precipitate.
［試験例１１：うがい薬（希釈後）の泡立ち抑制評価］
ＪＩＳの泡立ち試験を参照（ＪＩＳ Ｋ３３６２－２００８ ８．５起泡力及び泡の安定度、ロス・マイルス法参照）し、以下の手順にて実施例７～１０及び比較例９～１７のうがい薬の泡立ち試験を行った。
５０ｍＬビュレットに各うがい薬（検体）約５０ｍＬを入れ、更に、１００ｍＬメスシリンダーに前記検体約２０ｍＬを加え、ビュレットの先端（コック側）からメスシリンダー中の検液の液面まで約４５ｃｍとなるようにビュレットを設置した。
ビュレットのコックを全開にし、全量をメスシリンダーに加え、直ちに生じた泡の高さを測定し、下記基準により泡立ち抑制について評価し、得られた結果を表７に示す。
＜うがい薬（希釈後）泡立ち抑制 評価基準＞
〇：０～１０ｃｍ
△：１０．５～１２．５ｃｍ
×：１３．０ｃｍ以上
[Test Example 11: Evaluation of foaming inhibition of mouthwash (after dilution)]
Referring to the JIS foaming test (JIS K3362-2008 8.5 Foaming power and foam stability, Ross-Miles method), the mouthwashes of Examples 7 to 10 and Comparative Examples 9 to 17 were subjected to a foaming test according to the following procedure.
Approximately 50 mL of each mouthwash (specimen) was placed in a 50 mL burette, and approximately 20 mL of the specimen was added to a 100 mL measuring cylinder. The burette was placed so that the tip (cock side) of the burette was approximately 45 cm from the liquid level of the test liquid in the measuring cylinder.
The cock of the burette was fully opened and the entire amount was added to a measuring cylinder. The height of the foam that immediately formed was measured and the foaming inhibition was evaluated according to the following criteria. The results are shown in Table 7.
<Garment (diluted) foam suppression evaluation criteria>
○: 0 to 10 cm
△: 10.5-12.5cm
×: 13.0 cm or more
本処方では、うがい薬原液中の室温における結晶析出（原液の外観）、またうがい薬原液の滴下（希釈操作時）の結晶析出及びうがい薬（希釈後）の液の濁度並びに低温（５℃）下における結晶析出を抑制する目的で、ポリオキシエチレン硬化ヒマシ油類の代わりに
可溶化剤として知られている界面活性剤を種々変更して配合した場合の効果を評価した。またうがい薬の使用感（希釈後の甘味）や（希釈後の）泡立ち抑制についても評価した。
本発明の（Ｄ）成分であるポリオキシエチレン硬化ヒマシ油類は、希釈操作時の結晶析出抑制効果（原液の滴下）及びうがい薬（希釈後）の使用感（甘味）が多少低下するグレードがあるものの、原液の外観、結晶析出抑制効果（液の濁度、低温下における結晶析出）及び泡立ち抑制効果は良好であり、すべての評価において概ね満足できる結果となった。（実施例７～１０）
可溶化剤としてラウリン酸デカグリセリルを用いた場合、うがい薬原液の滴下（希釈操作時）において結晶析出が確認され、また原液の外観に濁りが生じ、うがい薬（希釈後）の使用感（甘味）及び泡立ち抑制効果についても低下する傾向がみられた。（比較例９）
またポリソルベート類は、全てのグレードでうがい薬原液の滴下（希釈操作時）において結晶析出が認められ、また原液の外観、うがい薬（希釈後）の使用感（甘味）、泡立ち抑制効果において低下するグレードが認められた。（比較例１０～１３）
ラウロマクロゴール類は、全てのグレードでうがい薬（希釈後）の低温下の保存において結晶析出があり、また泡立ち抑制効果が低く、うがい薬（希釈後）の使用感（甘味）やうがい薬原液の滴下（希釈操作時）の結晶析出評価にもやや劣る結果となった。（比較例１４及び１５）
ポリオキシエチレンオレイルエーテル類は、使用感が悪いグレードや、うがい薬（希釈後）の低温下の保存において結晶析出が認められるグレードがあった。（比較例１６及び１７）
以上の結果から、うがい薬（希釈後）の使用感（甘味）及び泡立ち抑制効果を損なうことなく、うがい薬原液中の室温における結晶析出（原液の外観）、うがい薬原液の滴下（希釈操作時）の室温における結晶析出抑制（目視）及びうがい薬（希釈後）の液の濁度評価による結晶析出抑制、並びに低温下（５℃）における結晶析出抑制（目視）を満足できる可溶化剤としては、ポリオキシエチレン硬化ヒマシ油類が良好であることがわかった。
In this formulation, in order to suppress crystal precipitation in the undiluted mouthwash solution at room temperature (appearance of the undiluted solution), crystal precipitation when the undiluted mouthwash solution is dripped (during dilution), the turbidity of the mouthwash solution (after dilution), and crystal precipitation at low temperature (5°C), the effects of various surfactants known as solubilizers instead of polyoxyethylene hydrogenated castor oils were evaluated. The feeling of use of the mouthwash (sweetness after dilution) and suppression of foaming (after dilution) were also evaluated.
Although the polyoxyethylene hydrogenated castor oils, which are component (D) of the present invention, have some grades in which the crystal precipitation suppression effect during dilution (dropping of the stock solution) and the feeling of use (sweetness) of the mouthwash (after dilution) are somewhat reduced, the appearance of the stock solution, the crystal precipitation suppression effect (turbidity of the liquid, crystal precipitation at low temperatures) and the foaming suppression effect are good, and the results of all evaluations were generally satisfactory. (Examples 7 to 10)
When decaglyceryl laurate was used as a solubilizer, crystal precipitation was confirmed when the mouthwash concentrate was dripped (during dilution), the appearance of the concentrate became cloudy, and the mouthwash (after dilution) also showed a tendency to have a reduced feel (sweetness) and foaming suppression effect (Comparative Example 9).
In addition, for all grades of polysorbates, crystal precipitation was observed when the undiluted mouthwash solution was dripped (during dilution), and some grades were found to be inferior in appearance of the undiluted solution, in the feel (sweetness) of the mouthwash (after dilution), and in the foaming suppression effect (Comparative Examples 10 to 13).
All grades of lauromacrogols were found to crystallize when stored at low temperatures as diluted mouthwash, and the foaming suppression effect was low. The mouthwash (diluted) was also slightly inferior in terms of usability (sweetness) and crystal precipitation evaluation when dripping the mouthwash concentrate (during dilution) (Comparative Examples 14 and 15).
Polyoxyethylene oleyl ethers include grades that have a poor feel when used and grades in which crystal precipitation was observed when the mouthwash (after dilution) was stored at low temperatures (Comparative Examples 16 and 17).
From the above results, it was found that polyoxyethylene hydrogenated castor oils are good solubilizers that can satisfy the following requirements without compromising the feel (sweetness) and foaming inhibition effect of the mouthwash (after dilution): crystal precipitation in the mouthwash concentrate at room temperature (appearance of the concentrate), crystal precipitation inhibition at room temperature when the mouthwash concentrate is dripped (during the dilution operation) (visual inspection), crystal precipitation inhibition based on turbidity evaluation of the mouthwash (after dilution), and crystal precipitation inhibition at low temperature (5°C) (visual inspection).
［うがい薬原液及びうがい薬の調製（４）］
〈実施例１１〉
ポリオキシエチレン硬化ヒマシ油６０ ０．５ｇを加熱して溶解後、プロピレングリコール ５５ｇに溶解した。ここに、エタノール ７．５ｍＬ、グリセリン脂肪酸エステル
０．１ｇ、セチルピリジニウム塩化物水和物 １．２５ｇ及びｌ－メントール １ｇを加えて室温下、撹拌して溶解させ、セチルピリジニウム相とした。
次に、精製水 ３０ｇに、サッカリンナトリウム １ｇ及びヒプロメロース９０ＳＨ－４０００ＳＲ ０．１５ｇを加えて室温下、撹拌して溶解させ、矯味剤相とした。
前記セチルピリジニウム相に前記矯味剤相を加えて、室温下撹拌して溶解させた後、アズレンスルホン酸ナトリウム ０．５ｇ及び適量のｐＨ調節剤を加えて溶解させ、精製水を加えて全量１００ｍＬとし、実施例１１のうがい薬原液（ｐＨ７．５）を得た（表８）。
うがい薬原液 ０．４ｍＬを、水 １００ｍＬに希釈し、実施例１１のうがい薬を得た（表９）。
[Preparation of mouthwash stock solution and mouthwash (4)]
Example 11
0.5 g of polyoxyethylene hydrogenated castor oil 60 was dissolved by heating, and then dissolved in 55 g of propylene glycol. 7.5 mL of ethanol, 0.1 g of glycerin fatty acid ester, 1.25 g of cetylpyridinium chloride hydrate, and 1 g of 1-menthol were added thereto, and dissolved by stirring at room temperature to obtain a cetylpyridinium phase.
Next, 1 g of sodium saccharin and 0.15 g of hypromellose 90SH-4000SR were added to 30 g of purified water and dissolved by stirring at room temperature to obtain a flavoring agent phase.
The flavoring agent phase was added to the cetylpyridinium phase and dissolved by stirring at room temperature, after which 0.5 g of sodium azulene sulfonate and an appropriate amount of pH adjuster were added and dissolved, and purified water was added to make up a total volume of 100 mL to obtain the mouthwash concentrate (pH 7.5) of Example 11 (Table 8).
0.4 mL of the mouthwash concentrate was diluted with 100 mL of water to obtain the mouthwash of Example 11 (Table 9).
〈比較例１８〉
グリセリン脂肪酸エステルの配合量を０．０５ｇ及びポリオキシエチレン硬化ヒマシ油６０の配合量を０．１０ｇに変え、セチルピリジニウム相にポリソルベート８０を０．３０ｇ配合したほかは実施例１１と同様にして、比較例１８のうがい薬原液及びうがい薬を得た。
〈比較例１９〉
ポリオキシエチレン硬化ヒマシ油６０の配合量を０．１０ｇに変え、セチルピリジニウム相にポリソルベート８０を０．３０ｇ配合したほかは実施例１１と同様にして、比較例１９のうがい薬原液及びうがい薬を得た。
〈比較例２０〉
セチルピリジニウム相にポリソルベート８０を０．０５ｇ配合したほかは実施例１１と同様にして、比較例２０のうがい薬原液及びうがい薬を得た。
〈比較例２１〉
セチルピリジニウム相にポリソルベート８０を０．１０ｇ配合したほかは実施例１１と同様にして、比較例２１のうがい薬原液及びうがい薬を得た。
〈比較例２２〉
セチルピリジニウム相にポリソルベート８０を０．３０ｇ配合したほかは実施例１１と同様にして、比較例２２のうがい薬原液及びうがい薬を得た。
Comparative Example 18
The mouthwash concentrate and mouthwash of Comparative Example 18 were obtained in the same manner as in Example 11, except that the amount of glycerin fatty acid ester was changed to 0.05 g and the amount of polyoxyethylene hydrogenated castor oil 60 was changed to 0.10 g, and 0.30 g of polysorbate 80 was added to the cetylpyridinium phase.
Comparative Example 19
A mouthwash concentrate and mouthwash of Comparative Example 19 were obtained in the same manner as in Example 11, except that the amount of polyoxyethylene hydrogenated castor oil 60 was changed to 0.10 g and 0.30 g of polysorbate 80 was added to the cetylpyridinium phase.
Comparative Example 20
A mouthwash concentrate and mouthwash of Comparative Example 20 were obtained in the same manner as in Example 11, except that 0.05 g of polysorbate 80 was added to the cetylpyridinium phase.
Comparative Example 21
A mouthwash concentrate and mouthwash of Comparative Example 21 were obtained in the same manner as in Example 11, except that 0.10 g of polysorbate 80 was added to the cetylpyridinium phase.
Comparative Example 22
A mouthwash concentrate and mouthwash of Comparative Example 22 were obtained in the same manner as in Example 11, except that 0.30 g of polysorbate 80 was added to the cetylpyridinium phase.
実施例１１及び比較例１８～２２で調製したうがい薬原液の処方を表８に、またうがい薬（希釈後）の処方を表９に、夫々示す。 The formulations of the mouthwash concentrates prepared in Example 11 and Comparative Examples 18 to 22 are shown in Table 8, and the formulations of the mouthwashes (after dilution) are shown in Table 9.
［試験例１２：原液の希釈操作時の結晶析出評価］
５０ｍＬビーカーに水道水５０ｍＬを入れ、そこに実施例１１及び比較例１８～２２のうがい薬原液を適量滴下した。滴下して５分間放置後、結晶析出の有無を目視にて確認し、下記基準により評価した。
＜原液の希釈操作時の結晶析出 評価基準＞
〇：結晶析出しない
×：結晶析出した
[Test Example 12: Evaluation of crystal precipitation during dilution of stock solution]
50 mL of tap water was placed in a 50 mL beaker, and an appropriate amount of the mouthwash concentrate of Example 11 and Comparative Examples 18 to 22 was dropped into it. After leaving it for 5 minutes, the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria.
<Crystallization criteria when diluting stock solution>
◯: No crystallization occurred ×: Crystallization occurred
［試験例１３：希釈時の濁り評価］
実施例１１及び比較例１８～２２のうがい薬を調製後、紫外可視分光光度計（ＵＶ－１６００、（株）島津製作所）を用いて、波長６６０ｎｍで濁度（ＯＤ６６０）を測定し、下記評価基準にて評価した。
＜希釈時の濁り（濁度：ＯＤ６６０） 評価基準＞
〇：０．０２０以下
△：０．０２０～０．０２５
×：０．０２６以上
[Test Example 13: Evaluation of turbidity upon dilution]
After preparing the mouthwashes of Example 11 and Comparative Examples 18 to 22, the turbidity (OD 660 ) was measured at a wavelength of 660 nm using an ultraviolet-visible spectrophotometer (UV-1600, Shimadzu Corporation) and evaluated according to the following evaluation criteria.
<Evaluation criteria for turbidity (turbidity: OD 660 ) upon dilution>
◯: 0.020 or less △: 0.020 to 0.025
×: 0.026 or more
［試験例１４：低温保存時（５℃）の結晶析出評価］
実施例１１及び比較例１８～２２のうがい薬（希釈後）を使用し、これを５℃にて７日間保存した後、結晶析出の有無を目視にて確認し、下記基準により評価した。
＜低温保存時の結晶析出評価基準＞
〇：結晶析出しない
×：結晶析出した
[Test Example 14: Evaluation of crystal precipitation during low-temperature storage (5°C)]
The mouthwashes (diluted) of Example 11 and Comparative Examples 18 to 22 were used and stored at 5° C. for 7 days, after which the presence or absence of crystal precipitation was visually confirmed and evaluated according to the following criteria.
<Crystallization criteria during low-temperature storage>
◯: No crystallization occurred ×: Crystallization occurred
また、実施例１１及び比較例１８～２２のうがい薬について、前述の［試験例１：使用感（矯味）］及び［試験例２：泡立ち抑制評価］の手順に従い、うがい薬の使用感（矯味）及び泡立ち抑制について評価した。
これらの結果をあわせて表９に示す。
In addition, the mouthwashes of Example 11 and Comparative Examples 18 to 22 were evaluated for usability (taste masking) and foaming inhibition according to the procedures described above in [Test Example 1: Usability (taste masking)] and [Test Example 2: Foaming inhibition evaluation].
These results are shown together in Table 9.
表８及び表９に示すように、うがい薬原液においてポリオキシエチレン硬化ヒマシ油６０の配合量を０．１％とし、代わりにポリソルベート８０を０．３０％配合した場合は、グリセリン脂肪酸エステルの配合量を変えても、使用感（矯味）、希釈時の結晶析出、低温保存時の結晶析出及び泡立ちを抑制することは困難であった（比較例１８及び１９）。
またうがい薬原液においてポリオキシエチレン硬化ヒマシ油６０を０．５％に増量した場合（ポリソルベート：０．３０％配合、比較例２２）は、前述の比較例１０と比べて希釈時及び低温保存時の結晶析出抑制に改善がみられたが、使用感（矯味）に欠けたままの結果となり、ポリソルベート８０の配合量が０．１％以下では、使用感（矯味）は改善するものの、希釈時の濁りが生じた（比較例２０及び２１）。また、ポリソルベート８０を０．０５～０．３％の範囲で配合した比較例２０～２２のいずれも、泡立ち抑制がされなかった。以上の結果より、ポリソルベート８０の配合は、特に泡立ち抑制の観点から、少量であっても好ましくないことが確認された。
一方で、グリセリン脂肪酸エステルを０．１％、ポリオキシエチレン硬化ヒマシ油６０
を０．５％配合し、ポリソルベート８０を配合しない実施例１１は、使用感、希釈時の析出、希釈時の濁り、低温保存時の結晶析出及び泡立ち抑制効果に優れていた。
As shown in Tables 8 and 9, when the amount of polyoxyethylene hydrogenated castor oil 60 in the mouthwash concentrate was 0.1% and 0.30% of polysorbate 80 was added instead, it was difficult to suppress the feel (flavor masking), crystal precipitation upon dilution, and crystal precipitation and foaming during storage at low temperatures, even if the amount of glycerin fatty acid ester was changed (Comparative Examples 18 and 19).
In addition, when the amount of polyoxyethylene hydrogenated castor oil 60 in the mouthwash concentrate was increased to 0.5% (polysorbate: 0.30%, Comparative Example 22), the inhibition of crystal precipitation during dilution and low-temperature storage was improved compared to the above-mentioned Comparative Example 10, but the result was that the feeling of use (flavor masking) was still lacking, and when the amount of polysorbate 80 was 0.1% or less, the feeling of use (flavor masking) was improved, but turbidity occurred when diluted (Comparative Examples 20 and 21). In addition, in all of Comparative Examples 20 to 22, in which polysorbate 80 was blended in the range of 0.05 to 0.3%, foaming was not suppressed. From the above results, it was confirmed that the blending of polysorbate 80 is not preferable, even in small amounts, especially from the viewpoint of foaming inhibition.
On the other hand, glycerin fatty acid ester was 0.1% and polyoxyethylene hydrogenated castor oil 60
Example 11, which contained 0.5% of polysorbate 80 and no polysorbate 80, was excellent in terms of feel when used, precipitation upon dilution, turbidity upon dilution, and the effects of inhibiting crystal precipitation and foaming during storage at low temperatures.
以上の結果から、アズレンスルホン酸及び／又はその塩、セチルピリジニウム及び／又はその塩及びｌ－メントールを含有するうがい薬において、（Ａ）特定の矯味剤、（Ｂ）多価アルコール脂肪酸エステル、（Ｃ）セルロース類、（Ｄ）ポリオキシエチレン硬化ヒマシ油類の配合により、うがい薬の使用感、泡立ち抑制、液垂れ抑制及び結晶析出抑制のすべてにおいて満足する効果を得られることが確認された。
そして上記（Ｂ）～（Ｄ）成分を配合し、矯味剤として紹介されている別の化合物を配合した場合にはうがい薬の使用感において満足する結果を得られず、（Ａ）特定の矯味剤を用いない場合には泡立ち抑制効果を全く得られず、（Ａ）特定の矯味剤を用いた場合においても（Ｂ）及び（Ｃ）成分のいずれか若しくは両方を配合しない場合には満足する泡立ち抑制効果を得ることができない結果となり、（Ｃ）成分を未配合とした場合には液垂れ抑制効果を得らない結果となった。そして（Ｄ）成分を未配合とした場合は結晶析出抑制効果を得られず、また、界面活性剤であるラウリン酸デカグリセリルやポリソルベート類、ラウロマウロゴール類、ポリオキシエチレンオレイルエーテル類では結晶析出抑制、泡立ち抑制、使用感（矯味・甘み）のすべてを満足する結果を得ることはできない結果となった。
From the above results, it has been confirmed that in a mouthwash containing azulene sulfonic acid and/or its salts, cetylpyridinium and/or its salts, and 1-menthol, the combination of (A) a specific flavoring agent, (B) a polyhydric alcohol fatty acid ester, (C) a cellulose compound, and (D) a polyoxyethylene hydrogenated castor oil compound provides satisfactory effects in terms of the mouthwash's feel when used, as well as in terms of foaming inhibition, dripping inhibition, and crystal precipitation inhibition.
And when the above (B) to (D) components are mixed and another compound introduced as a flavoring agent is mixed, the mouthwash does not have a satisfactory feeling when used, when the specific flavoring agent (A) is not used, no foaming suppression effect is obtained, when the specific flavoring agent (A) is used, the foaming suppression effect is not obtained when either or both of the (B) and (C) components are not mixed, and when the (C) component is not mixed, the dripping suppression effect is not obtained.And when the (D) component is not mixed, the crystal precipitation suppression effect is not obtained, and when the surfactants decaglyceryl laurate, polysorbates, lauromaurogols, and polyoxyethylene oleyl ethers are used, the crystal precipitation suppression, foaming suppression, and feeling when used (flavoring and sweetness) are not all satisfactory.
Claims (1)
（Ａ）サッカリンナトリウム及びアセスルファムカリウムから選択される１種以上の矯味剤、
（Ｂ）グリセリン脂肪酸エステル、
（Ｃ）ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース及びヒプロメロースからなる群から選択される１種以上であるセルロース類、
（Ｄ）ポリオキシエチレン硬化ヒマシ油５、ポリオキシエチレン硬化ヒマシ油１０、ポリオキシエチレン硬化ヒマシ油２０、ポリオキシエチレン硬化ヒマシ油４０、ポリオキシエチレン硬化ヒマシ油５０、ポリオキシエチレン硬化ヒマシ油６０及びポリオキシエチレン硬化ヒマシ油１００からなる群から選択される１種以上であるポリオキシエチレン硬化ヒマシ油類。 A mouthwash characterized in that the liquid composition contains azulene sulfonic acid and/or a salt thereof, cetylpyridinium and/or a salt thereof, and 1-menthol, and further contains the following components (A), (B), (C), and (D) (excluding a betaine acetate surfactant and polysorbate 80) :
(A) one or more flavoring agents selected from saccharin sodium and acesulfame potassium;
(B) glycerin fatty acid ester ,
(C) one or more celluloses selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, and hypromellose ;
(D) Polyoxyethylene hydrogenated castor oils which are one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene hydrogenated castor oil 100.
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