JP5372573B2 - Antibacterial agent and preparation comprising the same - Google Patents
Antibacterial agent and preparation comprising the same Download PDFInfo
- Publication number
- JP5372573B2 JP5372573B2 JP2009083380A JP2009083380A JP5372573B2 JP 5372573 B2 JP5372573 B2 JP 5372573B2 JP 2009083380 A JP2009083380 A JP 2009083380A JP 2009083380 A JP2009083380 A JP 2009083380A JP 5372573 B2 JP5372573 B2 JP 5372573B2
- Authority
- JP
- Japan
- Prior art keywords
- mono
- glyceryl ether
- antibacterial
- hydroxyphenylethyl
- antibacterial agent
- 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
- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims description 7
- 239000003814 drug Substances 0.000 claims abstract description 18
- 229940079593 drug Drugs 0.000 claims abstract description 14
- SNVMPBUIACMYPW-UHFFFAOYSA-N 3-[2-(4-hydroxyphenyl)ethoxy]propane-1,2-diol Chemical compound OCC(O)COCCC1=CC=C(O)C=C1 SNVMPBUIACMYPW-UHFFFAOYSA-N 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 5
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 28
- 239000002537 cosmetic Substances 0.000 abstract description 19
- 239000007788 liquid Substances 0.000 abstract description 10
- 239000002253 acid Substances 0.000 abstract description 8
- 235000013305 food Nutrition 0.000 abstract description 8
- 150000002148 esters Chemical class 0.000 abstract description 7
- 206010040880 Skin irritation Diseases 0.000 abstract description 6
- 230000036556 skin irritation Effects 0.000 abstract description 6
- 231100000475 skin irritation Toxicity 0.000 abstract description 6
- 239000003755 preservative agent Substances 0.000 abstract description 3
- 230000002335 preservative effect Effects 0.000 abstract description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 abstract description 2
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 2
- 230000007815 allergy Effects 0.000 abstract description 2
- 238000011109 contamination Methods 0.000 abstract 1
- 230000000813 microbial effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- -1 cationic amino acid derivatives Chemical class 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 7
- 235000006708 antioxidants Nutrition 0.000 description 7
- 239000002304 perfume Substances 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- YCCILVSKPBXVIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)ethanol Chemical class OCCC1=CC=C(O)C=C1 YCCILVSKPBXVIP-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000003078 antioxidant effect Effects 0.000 description 6
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 description 6
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 6
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 5
- 229940058015 1,3-butylene glycol Drugs 0.000 description 4
- 235000019437 butane-1,3-diol Nutrition 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
- 239000000419 plant extract Substances 0.000 description 4
- 235000015320 potassium carbonate Nutrition 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WTVHAMTYZJGJLJ-UHFFFAOYSA-N (+)-(4S,8R)-8-epi-beta-bisabolol Natural products CC(C)=CCCC(C)C1(O)CCC(C)=CC1 WTVHAMTYZJGJLJ-UHFFFAOYSA-N 0.000 description 3
- RGZSQWQPBWRIAQ-CABCVRRESA-N (-)-alpha-Bisabolol Chemical compound CC(C)=CCC[C@](C)(O)[C@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-CABCVRRESA-N 0.000 description 3
- 229940031723 1,2-octanediol Drugs 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 3
- NCZPCONIKBICGS-UHFFFAOYSA-N 3-(2-ethylhexoxy)propane-1,2-diol Chemical compound CCCCC(CC)COCC(O)CO NCZPCONIKBICGS-UHFFFAOYSA-N 0.000 description 3
- VVRUMNNFYXYHOF-UHFFFAOYSA-N 3-octan-3-yloxypropane-1,2-diol Chemical compound CCCCCC(CC)OCC(O)CO VVRUMNNFYXYHOF-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LKUNXBRZDFMZOK-GFCCVEGCSA-N Capric acid monoglyceride Natural products CCCCCCCCCC(=O)OC[C@H](O)CO LKUNXBRZDFMZOK-GFCCVEGCSA-N 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- RGZSQWQPBWRIAQ-LSDHHAIUSA-N alpha-Bisabolol Natural products CC(C)=CCC[C@@](C)(O)[C@@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-LSDHHAIUSA-N 0.000 description 3
- TUFYVOCKVJOUIR-UHFFFAOYSA-N alpha-Thujaplicin Natural products CC(C)C=1C=CC=CC(=O)C=1O TUFYVOCKVJOUIR-UHFFFAOYSA-N 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 229940036350 bisabolol Drugs 0.000 description 3
- HHGZABIIYIWLGA-UHFFFAOYSA-N bisabolol Natural products CC1CCC(C(C)(O)CCC=C(C)C)CC1 HHGZABIIYIWLGA-UHFFFAOYSA-N 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 150000002009 diols Chemical class 0.000 description 3
- 125000003827 glycol group Chemical group 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 3
- AEIJTFQOBWATKX-UHFFFAOYSA-N octane-1,2-diol Chemical compound CCCCCCC(O)CO AEIJTFQOBWATKX-UHFFFAOYSA-N 0.000 description 3
- 229960005323 phenoxyethanol Drugs 0.000 description 3
- LKUNXBRZDFMZOK-UHFFFAOYSA-N rac-1-monodecanoylglycerol Chemical compound CCCCCCCCCC(=O)OCC(O)CO LKUNXBRZDFMZOK-UHFFFAOYSA-N 0.000 description 3
- 229940032094 squalane Drugs 0.000 description 3
- 229930007845 β-thujaplicin Natural products 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- HCIFMENZOKGFEI-UHFFFAOYSA-N 1-(4-phenoxyphenyl)ethanol Chemical compound C1=CC(C(O)C)=CC=C1OC1=CC=CC=C1 HCIFMENZOKGFEI-UHFFFAOYSA-N 0.000 description 2
- QXYGLKUCFDGMMX-UHFFFAOYSA-N 2-(4-hydroxyphenyl)propane-1,2-diol Chemical compound OCC(O)(C)C1=CC=C(O)C=C1 QXYGLKUCFDGMMX-UHFFFAOYSA-N 0.000 description 2
- YUHRMZDJCZCFMD-UHFFFAOYSA-N 3-[2-(4-ethoxyphenyl)ethoxy]propane-1,2-diol Chemical compound C(C(O)CO)OCCC1=CC=C(C=C1)OCC YUHRMZDJCZCFMD-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000228245 Aspergillus niger Species 0.000 description 2
- OYXXDWBBVDQZLI-UHFFFAOYSA-N COC1=CC=C(CCOCC(CO)O)C=C1 Chemical compound COC1=CC=C(CCOCC(CO)O)C=C1 OYXXDWBBVDQZLI-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- DBLDQZASZZMNSL-QMMMGPOBSA-N L-tyrosinol Natural products OC[C@@H](N)CC1=CC=C(O)C=C1 DBLDQZASZZMNSL-QMMMGPOBSA-N 0.000 description 2
- 239000004909 Moisturizer Substances 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229940119170 jojoba wax Drugs 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000001333 moisturizer Effects 0.000 description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- WCVRQHFDJLLWFE-UHFFFAOYSA-N pentane-1,2-diol Chemical compound CCCC(O)CO WCVRQHFDJLLWFE-UHFFFAOYSA-N 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229960002477 riboflavin Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 235000004330 tyrosol Nutrition 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- 229940015975 1,2-hexanediol Drugs 0.000 description 1
- WQNHWIYLCRZRLR-UHFFFAOYSA-N 2-(3-hydroxy-2,5-dioxooxolan-3-yl)acetic acid Chemical compound OC(=O)CC1(O)CC(=O)OC1=O WQNHWIYLCRZRLR-UHFFFAOYSA-N 0.000 description 1
- CNMVSNTVPZWQMI-UHFFFAOYSA-N 2-(4-ethoxyphenyl)ethanol Chemical compound CCOC1=CC=C(CCO)C=C1 CNMVSNTVPZWQMI-UHFFFAOYSA-N 0.000 description 1
- XPOFTQCBYADFNA-UHFFFAOYSA-N 2-(4-ethoxyphenyl)propane-1,2-diol Chemical compound CCOC1=CC=C(C(C)(O)CO)C=C1 XPOFTQCBYADFNA-UHFFFAOYSA-N 0.000 description 1
- GNUVKNWVXJIZDX-UHFFFAOYSA-N 2-(4-methoxyphenyl)propane-1,2-diol Chemical compound COC1=CC=C(C(C)(O)CO)C=C1 GNUVKNWVXJIZDX-UHFFFAOYSA-N 0.000 description 1
- KNUPSOXBESCJLY-UHFFFAOYSA-N 2-methoxy-1-phenylhexan-1-one Chemical compound CCCCC(OC)C(=O)C1=CC=CC=C1 KNUPSOXBESCJLY-UHFFFAOYSA-N 0.000 description 1
- BXVSAYBZSGIURM-UHFFFAOYSA-N 2-phenoxy-4h-1,3,2$l^{5}-benzodioxaphosphinine 2-oxide Chemical compound O1CC2=CC=CC=C2OP1(=O)OC1=CC=CC=C1 BXVSAYBZSGIURM-UHFFFAOYSA-N 0.000 description 1
- IUUULXXWNYKJSL-UHFFFAOYSA-N 4-methoxy-alpha-methylbenzyl alcohol Chemical compound COC1=CC=C(C(C)O)C=C1 IUUULXXWNYKJSL-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- UQYOOUVXTXZNLK-UHFFFAOYSA-N C1=CC(=CC=C1CCC(C(CO)O)OC(CCC2=CC=C(C=C2)O)C(CO)O)O Chemical compound C1=CC(=CC=C1CCC(C(CO)O)OC(CCC2=CC=C(C=C2)O)C(CO)O)O UQYOOUVXTXZNLK-UHFFFAOYSA-N 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 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 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-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
- 239000000940 FEMA 2235 Substances 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 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
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- LXNHXLLTXMVWPM-UHFFFAOYSA-N Vitamin B6 Natural products CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008278 cosmetic cream Substances 0.000 description 1
- 229940071120 dehydroacetate Drugs 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 229940087068 glyceryl caprylate Drugs 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical class 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 1
- 239000008187 granular material Substances 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 235000019674 grape juice Nutrition 0.000 description 1
- 229940107702 grapefruit seed extract Drugs 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000000118 hair dye Substances 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition 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
- 229960002446 octanoic acid Drugs 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229940092258 rosemary extract Drugs 0.000 description 1
- 235000020748 rosemary extract Nutrition 0.000 description 1
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 description 1
- IKGXIBQEEMLURG-NVPNHPEKSA-N rutin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-NVPNHPEKSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015192 vegetable juice Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 239000011670 zinc gluconate Substances 0.000 description 1
- 235000011478 zinc gluconate Nutrition 0.000 description 1
- 229960000306 zinc gluconate Drugs 0.000 description 1
Landscapes
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
本発明は、抗菌剤に関するものであり、新規な化合物であるα−モノp−ヒドロキシフェニルエチルグリセリルエーテルに高い抗菌作用が認められ、一般的な防腐剤であるパラオキシ安息香酸に代わり皮膚外用剤に配合が期待できる。またα−モノp−ヒドロキシフェニルエチルグリセリルエーテルの抗菌作用を活かして、医薬品、医薬部外品や液状ドリンク剤の防腐剤としても適用可能である。 The present invention relates to an antibacterial agent, and α-mono p-hydroxyphenylethyl glyceryl ether, which is a novel compound, has a high antibacterial action. Mixing can be expected. In addition, the antibacterial action of α-mono p-hydroxyphenylethyl glyceryl ether can be utilized as a preservative for pharmaceuticals, quasi drugs and liquid drinks.
皮膚外用剤特に化粧品等は開封後、継続して繰り返し使用する製品等では外部から混入してくる微生物の増殖を抑制し、経時とともに死滅させ製品の劣化を防止する目的で抗菌剤が使用される。代表的なものとして、パラオキシ安息香酸エステルが汎用されている。特にパラオキシ安息香酸エステルは、食品にも汎用されているが、過去アレルギーが認められた経緯があり、皮膚刺激性の問題が指摘されたことから、化粧料への配合に関しては配合量の上限が規定されている。その他、安息香酸塩、サリチル酸塩やデヒドロ酢酸塩もよく使用されるがパラオキシ安息香酸エステルと同様に皮膚刺激の問題が指摘されている。 Antibacterial agents are used for the purpose of suppressing the growth of microorganisms mixed from the outside and preventing the product from deteriorating over time in products that are used repeatedly after opening the skin, especially cosmetics, etc. . As a representative one, paraoxybenzoic acid esters are widely used. In particular, paraoxybenzoic acid esters are widely used in foods, but due to the fact that past allergies have been observed and skin irritation problems have been pointed out, the upper limit of the amount to be added to cosmetics is limited. It is prescribed. In addition, benzoate, salicylate and dehydroacetate are often used, but skin irritation problems have been pointed out as with paraoxybenzoate.
とりわけ化粧品では近年、フェノキシエタノールによって抗菌性をもたせる動きがあるが、皮膚刺激の問題は回避できているとは言えない。また、天然系の抗菌性を有する物質としては、ヒノキチオール、モノカプリル酸グリセリド、カチオン系アミノ酸誘導体、ビサボロール、グリコール類、及び植物抽出液としてのローズマリー抽出液やグレープフルーツ種子抽出液等が知られており、それらを併用して微生物の増殖を抑えることも試されている。しかしながら、ヒノキチオールは、鉄イオンの存在下で褐変を起こすことが知られている。モノカプリル酸グリセリルは、加水分解により水存在下でエステル結合が分解し遊離したカプリル酸が発生する。その結果変臭の原因となる。また、植物抽出物系抗菌剤においては、活性成分が十分に確定されているわけではないために、ロットによる抗菌力のバラツキが生じ一定の抗菌性を保持することが難しい状況にある。このような観点から、これら種々の問題点をクリアする新たな抗菌剤の開発が求められている。そのような中、グリコール構造を有する1,2−オクタンジオール(特許文献1、非特許文献1)、α−2エチルヘキシルグリセリルエーテル(特許文献2、特許文献3、非特許文献2)やチロソール誘導体(特許文献4)が開発されている。 In particular, cosmetics have recently moved to antibacterial properties with phenoxyethanol, but the problem of skin irritation cannot be avoided. As natural antibacterial substances, hinokitiol, monocaprylic acid glycerides, cationic amino acid derivatives, bisabolol, glycols, rosemary extract and grapefruit seed extract as plant extracts are known. It has also been tried to suppress the growth of microorganisms by using them together. However, hinokitiol is known to brown in the presence of iron ions. Glyceryl monocaprylate generates caprylic acid liberated by hydrolysis of the ester bond in the presence of water by hydrolysis. As a result, it causes odor. Moreover, in the plant extract antibacterial agent, since the active ingredient is not sufficiently determined, the antibacterial activity varies from lot to lot and it is difficult to maintain a certain antibacterial property. From such a viewpoint, development of a new antibacterial agent that clears these various problems is demanded. Among them, 1,2-octanediol having a glycol structure (Patent Literature 1, Non-Patent Literature 1), α-2 ethylhexyl glyceryl ether (Patent Literature 2, Patent Literature 3, Non-Patent Literature 2) and a tyrosol derivative ( Patent document 4) has been developed.
パラオシキシ安息香酸と同様幅広い抗菌性を有しながら、安全性の高い抗菌剤を提供し、それを防腐力を必要とする製品に配合することによって安全性に優れた製品を提供することが本発明の課題である。 It is the present invention to provide a highly safe antibacterial agent having a wide range of antibacterial properties similar to paraoxyxybenzoic acid, and to provide a product with excellent safety by blending it with a product that requires antiseptic power. It is a problem.
そこで、本発明者は、かかる実情に鑑み鋭意検討した結果、グリコール構造と疎水基構造を有する化合物の中でα−モノp−ヒドロキシフェニルエチルグリセリルエーテルが低濃度、かつ幅広い抗菌スペクトルを有することを見出し、本発明の完成に至った。 Therefore, as a result of intensive studies in view of such circumstances, the present inventors have found that α-mono p-hydroxyphenylethyl glyceryl ether has a low concentration and a wide antibacterial spectrum among the compounds having a glycol structure and a hydrophobic group structure. The headline, the present invention has been completed.
即ち、本発明は、一般式1で示されるα−モノp−ヒドロキシフェニルエチルグリセリルエーテルからなる抗菌剤及びそれを配合してなる皮膚外用剤、医薬品、医薬部外品、食品および液状飲料である。 That is, the present invention is an antibacterial agent composed of α-mono p-hydroxyphenylethyl glyceryl ether represented by the general formula 1, and a skin external preparation, a pharmaceutical product, a quasi-drug, a food and a liquid beverage comprising the same. .
以下、本発明の構成について詳しく記述する。
本発明のα−モノp−ヒドロキシフェニルエチルグリセリルエーテルは、オリーブ中の抗炎症成分として知られるチロソールとグリセリンのα位でエーテル結合を有する化合物で、構造中に保湿剤としての機能を有する親水基であるグリコール構造を持っている。
Hereinafter, the configuration of the present invention will be described in detail.
The α-mono p-hydroxyphenylethyl glyceryl ether of the present invention is a compound having an ether bond at the α-position of tyrosol and glycerin, which is known as an anti-inflammatory component in olive, and has a hydrophilic group having a function as a moisturizer in the structure It has a glycol structure.
α−モノp−ヒドロキシフェニルエチルグリセリルエーテルの合成は、α−モノアルキルグリセリルエーテルの一般的な製造法によって得ることが可能である。それは、チロソールのヒドロキシ基を保護し、グリシドールと反応させ、α−位に選択的にエーテル結合を形成させる。その後、保護基をはずして目的物を得ることができる。 The synthesis of α-mono p-hydroxyphenyl ethyl glyceryl ether can be obtained by a general production method of α-monoalkyl glyceryl ether. It protects the hydroxy group of tyrosol and reacts with glycidol to selectively form an ether linkage at the α-position. Thereafter, the protecting group can be removed to obtain the desired product.
本発明のα−モノp−ヒドロキシフェニルエチルグリセリルエーテルは、単独でも十分な抗菌性を示すが、少量のフェノキシエタノール、ヒノキチオール、モノカプリル酸グリセリド、カチオン系アミノ酸誘導体、ビサボロールや1,2−ペンタンジオール、1,2−ヘキサンジオール等の抗菌剤や抗菌作用を有する植物抽出物などの併用やEDTAのようなキレート剤を併用することによって、抗菌作用の向上が期待できる。 The α-mono p-hydroxyphenylethyl glyceryl ether of the present invention alone exhibits sufficient antibacterial properties, but a small amount of phenoxyethanol, hinokitiol, monocaprylic acid glyceride, cationic amino acid derivatives, bisabolol and 1,2-pentanediol, By using a combination of an antibacterial agent such as 1,2-hexanediol, a plant extract having an antibacterial action, or a chelating agent such as EDTA, an improvement in the antibacterial action can be expected.
本発明の抗菌剤には、上記した必須成分の他に、その抗菌作用を妨げない範囲で通常の化粧品や医薬品、医薬部外品等に用いられる他の成分、例えば、ビタミンB2類、ビタミンB6類、ビタミンC類、ビタミンD類、ニコチン酸類、ビタミンE類、ビタミンP、ビオチン等のビタミン類、アミノ酸及びアミノ酸誘導体、ホホバ油、スクワラン等の油分、グリセリン、ソルビトール、1,3−ブチレングリコール等のグリコール類、コラーゲン、ヒアルロン酸等の高分子保湿剤、酸化防止剤、界面活性剤、グリチルリチン酸誘導体等の消炎剤、各種植物抽出物、カルボキシビニルポリマー等の増粘剤、香料、水、アルコール、色剤、ポリエチレン等の樹脂粉末等を必要に応じて適宜配合することができる。 In addition to the above-mentioned essential components, the antibacterial agent of the present invention includes other components used for normal cosmetics, pharmaceuticals, quasi drugs, etc. within the range that does not interfere with the antibacterial action, such as vitamin B2 and vitamin B6. , Vitamin C, vitamin D, nicotinic acid, vitamin E, vitamin P, vitamins such as biotin, amino acids and amino acid derivatives, jojoba oil, oil such as squalane, glycerin, sorbitol, 1,3-butylene glycol, etc. Glycols, collagen, hyaluronic acid and other polymer moisturizers, antioxidants, surfactants, anti-inflammatory agents such as glycyrrhizic acid derivatives, various plant extracts, thickeners such as carboxyvinyl polymer, fragrance, water, alcohol In addition, resin powders such as colorants and polyethylene can be appropriately blended as necessary.
本発明にかかるα−モノp−ヒドロキシフェニルエチルグリセリルエーテルの製品に対する配合量であるが、例えば化粧料に配合する場合を例にすると、化粧料の実施態様、化粧料の使用形態などに応じて変動させることが可能で特に限定されないが、原則的には、化粧料中に有効量存在すれば良いが、一般的な配合量は、化粧料組成物中0.0001〜5質量%であり、好ましくは0.01〜2質量%、更に好ましくは0.05〜0.5質量%であるが、化粧料の剤型や処方内容により適正量は特に限定することはできないための目安である。 Although it is the compounding quantity with respect to the product of (alpha) -mono p-hydroxyphenyl ethyl glyceryl ether concerning this invention, when it mix | blends with the example of cosmetics, for example, according to the embodiment of cosmetics, the usage form of cosmetics, etc. Although it can be varied and is not particularly limited, in principle, an effective amount may be present in the cosmetic, but the general blending amount is 0.0001 to 5% by mass in the cosmetic composition, Preferably it is 0.01-2 mass%, More preferably, it is 0.05-0.5 mass%, but it is a standard because an appropriate amount cannot be specifically limited by the dosage form and prescription content of cosmetics.
本発明にかかる化粧料への適用範囲は、剤型等による制限はなく、全ての化粧料に適用が可能である。同様に液状の医薬品、医薬部外品や食品のドリンク剤にも同様である。 The range of application to the cosmetic according to the present invention is not limited by the dosage form, and can be applied to all cosmetics. The same applies to liquid medicines, quasi drugs and food drinks.
例えば、本発明にかかるα−モノp−ヒドロキシフェニルエチルグリセリルエーテルは、各種の内用・外用製剤類(動物用に使用する製剤も含む)全般において利用でき、具体的には、アンプル状、カプセル状、丸剤、錠剤状、粉末状、顆粒状、固形状、液状、ゲル状又は気泡状の1)医薬品類、2)医薬部外品類、3)食品類、4)局所用又は全身用の皮膚化粧品類、5)頭皮・頭髪に適用する薬用又は/及び化粧用の製剤類(例えば、シャンプー剤、リンス剤、トリートメント剤、パーマネント液、染毛料、整髪料、ヘアートニック剤、育毛・養毛料など)、6)浴湯に投じて使用する浴用剤、7)その他、液臭・防臭防止剤や衛生用品、衛生綿類、ウエットティシュなどが上げられる。
更に液状飲料類としては、医薬品や医薬部外品の栄養ドリンク、一般食品の果実ジュース、野菜ジュース、乳清飲料、清涼飲料、酒類などの飲料、その他、健康食品など一般的な飲料類への使用が上げられる。
For example, α-mono p-hydroxyphenylethyl glyceryl ether according to the present invention can be used in various internal and external preparations (including preparations used for animals), specifically, ampoules, capsules Pills, tablets, powders, granules, solids, liquids, gels or bubbles 1) pharmaceuticals, 2) quasi drugs, 3) foods, 4) topical or systemic Skin cosmetics, 5) Medicinal or / and cosmetic preparations applied to the scalp and hair (eg shampoos, rinses, treatments, permanent liquids, hair dyes, hair styling agents, hair styling agents, hair growth and hair restorations 6) Bathing agents used in bath water, 7) In addition, liquid odor / deodorant, hygiene products, sanitary cotton, wet tissue, etc.
In addition, liquid beverages include pharmaceutical and quasi-drug nutrition drinks, general food fruit juices, vegetable juices, whey drinks, soft drinks, alcoholic beverages, and other general beverages such as health foods. Increased use.
本発明によれば、α−モノp−ヒドロキシフェニルエチルグリセリルエーテルからなる抗菌剤によっ抗菌作用が幅広くかつ安全性に優れた抗菌剤を提供することができる。また、本発明の抗菌剤を使用することで、パラオキシ安息香酸エステルを使用せず十分な抗菌作用を有し、更に安全性に優れた製品をも提供することができる。 According to the present invention, an antibacterial agent having a wide antibacterial action and excellent safety can be provided by an antibacterial agent comprising α-mono p-hydroxyphenylethyl glyceryl ether. Further, by using the antibacterial agent of the present invention, it is possible to provide a product having sufficient antibacterial action without using a paraoxybenzoic acid ester and having excellent safety.
以下、本発明を実施例により更に具体的に説明するが、本発明は実施例に限定されることはない。
[α−モノp−ヒドロキシフェニルエチルグリセリルエーテルの製造]
まず、本発明にかかる皮膚外用剤において特徴的なα−モノp−ヒドロキシフェニルエチルグリセリルエーテルの製造例について説明する。
EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, this invention is not limited to an Example.
[Production of α-mono p-hydroxyphenylethyl glyceryl ether]
First, production examples of α-mono p-hydroxyphenylethyl glyceryl ether which is characteristic in the external preparation for skin according to the present invention will be described.
「α−モノp−ヒドロキシフェニルエチルグリセリルエーテル」3-(2-(4-ヒドロキシフェニル)-1,2-プロパンジオール
P−ヒドロキシフェニルエチルアルコール,塩化ベンジルとK2CO3の混合物をアセトン中,6時間加熱還流した.溶媒を除去し,酢酸エチル,水を加えて分液し,有機層を10 %NaOH,次いで水で洗浄,脱水,濃縮した.残留物を,酢酸エチルから再結晶して2-(4-フェノキシフェニルエタノール)を得た.
400 MHz 1H
NMR (CDCl3, 30 ℃) 2.81 (t, 2H, J = 6.6 Hz, -CH2CH2OH),
3.83 (t, 2H, J = 6.6 Hz, -CH2CH2OH),
5.05 (s, 2H, -OCH2Ar-), 6.91 (d, 2H, J = 8.4 Hz, ArH), 7.14 (d, 2H, J = 8.4 Hz, ArH),
7.30-7.44 (m, 5H, ArH).
2-(4-フェノキシフェニルエタノール) ( 2.8 mmol, 638 mg)、グリシドール ( 14.0 mmol, 1034 mg )、 K2CO3 (0.14 mmol, 19 mg ) の混合物をを130 ℃,6 h撹拌した。酢酸エチル,水を加えて分液し,有機層を脱水,濃縮,減圧乾燥し粗生成物 (583 mg)を得た.この粗生成物 (300 mg)をGPC 分取をおこない3-(2-(4-フェノキシフェニル))-1,2-プロパンジオール (55 mg)を得た.
400 MHz 1H
NMR (CDCl3, 30 ℃) 2.83 (t, 2H, J = 6.8 Hz, -Ar-CH2CH2-), 3.48-3.83 (m, 7H)
5.04 (s, 2H, -OCH2-Ar), 6.90 (d, 2H, J = 8.4 Hz, ArH), 7.12 (d, 2H, J = 8.4 Hz, ArH),
7.31-7.44 (m, 5H, Ar-H).
3-(2-(4-フェノキシフェニル))-1,2-プロパンジオール (0.4 mmol, 126 mg) とPd-C (50mg) にEtOH (5 ml)を加え, 水素雰囲気下50℃, 7 h撹拌した.Pd-C をろ過し,熱EtOH で洗浄し,濃縮, 減圧乾燥し,α−モノp−ヒドロキシフェニルエチルグリセリルエーテル[3-(2-(4-ヒドロキシフェニル)-1,2-プロパンジオール ) (76 mg, 86 %)を得た.
400 MHz 1H
NMR (CDCl3, 30 ℃) 2.82 (t, 2H, J = 7.0 Hz, -Ar-CH2-),
3.49-3.82 (m, 7H), 6.76 (d, 2H, J =
8.4 Hz, Ar-H), 7.07 (d, 2H, J = 8.4 Hz, Ar-H).
“Α-Mono p-hydroxyphenylethyl glyceryl ether” 3- (2- (4-hydroxyphenyl) -1,2-propanediol
A mixture of P-hydroxyphenylethyl alcohol, benzyl chloride and K 2 CO 3 was heated to reflux in acetone for 6 hours. The solvent was removed, ethyl acetate and water were added for liquid separation, and the organic layer was washed with 10% NaOH and then with water, dehydrated and concentrated. The residue was recrystallized from ethyl acetate to give 2- (4-phenoxyphenylethanol).
400 MHz 1 H
NMR (CDCl 3 , 30 ° C) 2.81 (t, 2H, J = 6.6 Hz, -CH 2 CH 2 OH),
3.83 (t, 2H, J = 6.6 Hz, -CH 2 CH 2 OH),
5.05 (s, 2H, -OCH 2 Ar-), 6.91 (d, 2H, J = 8.4 Hz, ArH), 7.14 (d, 2H, J = 8.4 Hz, ArH),
7.30-7.44 (m, 5H, ArH).
A mixture of 2- (4-phenoxyphenylethanol) (2.8 mmol, 638 mg), glycidol (14.0 mmol, 1034 mg), K2CO3 (0.14 mmol, 19 mg) was stirred at 130 ° C. for 6 h. did. Ethyl acetate and water were added for liquid separation, and the organic layer was dehydrated, concentrated and dried under reduced pressure to obtain a crude product (583 mg). This crude product (300 mg) was subjected to GPC fractionation to give 3- (2- (4-phenoxyphenyl))-1,2-propanediol (55 mg).
400 MHz 1 H
NMR (CDCl 3 , 30 ° C) 2.83 (t, 2H, J = 6.8 Hz, -Ar-CH 2 CH 2- ), 3.48-3.83 (m, 7H)
5.04 (s, 2H, -OCH 2 -Ar), 6.90 (d, 2H, J = 8.4 Hz, ArH), 7.12 (d, 2H, J = 8.4 Hz, ArH),
7.31-7.44 (m, 5H, Ar-H).
EtOH (5 ml) was added to 3- (2- (4-phenoxyphenyl))-1,2-propanediol (0.4 mmol, 126 mg) and Pd—C (50 mg). Stir for 7 h. Pd—C was filtered, washed with hot EtOH, concentrated and dried under reduced pressure, α-mono p-hydroxyphenylethylglyceryl ether [3- (2- (4-hydroxyphenyl) -1,2-propanediol) ( 76 mg, 86%).
400 MHz 1 H
NMR (CDCl 3 , 30 ° C) 2.82 (t, 2H, J = 7.0 Hz, -Ar-CH 2- ),
3.49-3.82 (m, 7H), 6.76 (d, 2H, J =
8.4 Hz, Ar-H), 7.07 (d, 2H, J = 8.4 Hz, Ar-H).
(比較例1)
p-フェネチルアルコール (100 mmol, 12.5 g), グリシドール (20 mmol, 1.48 g), K2CO3 (1.0 mmol, 139 mg)を130 ℃,6
h撹拌した.温ヘキサンを加え可溶部を取り除き,不溶部をクーゲル蒸留し減圧蒸留して,α−モノp−フェニルエチルグリセリルエーテル[3-(2-(4-フェニル)-1,2-プロパンジオール ) (1.00 g, 25 %)を得た.
400 MHz 1H
NMR (CDCl3, 30 ℃) 2.07 (t, 1H, J = 5.1 Hz, -OH),
2.52 (d, 1H, J = 5.1 Hz, -OH), 2.90 (t, 2H, J = 6.8 Hz, -Ar-CH2-),
3.49~3.85 (m, 7H), 7.20~7.32 (m, 5H, Ar-H)
125 MHz 13C
NMR (CDCl3, 30 ℃) 36.1 (ArCH2), 64.0 (-CH2OH)
70.5 (-CHOH-), 72.3 (-OCH2-), 72.4 (-OCH2-), 126.3,
128.4, 128.8, 138.6.
(Comparative Example 1)
p-phenethyl alcohol (100 mmol, 12.5 g), glycidol (20 mmol, 1.48 g), K2CO3 (1.0 mmol, 139 mg) at 130 ° C., 6
The mixture was stirred for h. Hot hexane was added to remove the soluble part, the insoluble part was subjected to Kugel distillation and vacuum distillation, and α-mono p-phenylethylglyceryl ether [3- (2- (4-phenyl) -1,2-propanediol) ( 1.00 g, 25%).
400 MHz 1 H
NMR (CDCl 3 , 30 ° C) 2.07 (t, 1H, J = 5.1 Hz, -OH),
2.52 (d, 1H, J = 5.1 Hz, -OH), 2.90 (t, 2H, J = 6.8 Hz, -Ar-CH 2- ),
3.49 ~ 3.85 (m, 7H), 7.20 ~ 7.32 (m, 5H, Ar-H)
125 MHz 13 C
NMR (CDCl 3 , 30 ° C) 36.1 (ArCH 2 ), 64.0 (-CH 2 OH)
70.5 (-CHOH-), 72.3 (-OCH 2- ), 72.4 (-OCH 2- ), 126.3,
128.4, 128.8, 138.6.
(比較例2)
p-メトキシフェニルエタノール (40 mmol, 6.01 g), グリシドール (20
mmol,
1.48
g), K2CO3 (0.5 mmol, 0.14 g)を130 ℃,6 h撹拌した.温ヘキサンを加え可溶部として未反応物を取り除き,不溶部を減圧蒸留して,α−モノp−メトキシフェニルエチルグリセリルエーテル3-(2-(4-メトキシフェニル)-1,2-プロパンジオール(1.10 g) を得た.
400 MHz 1H
NMR (CDCl3, 30 ℃) 2.14 (t, 1H, J = 5.1 Hz, -OH),
2.56 (d, 1H, J=5.1 Hz, -OH), 2.83 (t, 2H, J = 6.6 Hz, -Ar-CH2-),
3.49~3.82 (m, 7H) 3.79 (s, 3H, -OCH3), 6.84 (d, 2H, J = 8.6 Hz, Ar-H), 7.12 (d, 2H, J = 8.6 Hz, Ar-H).
125 MHz 13C
NMR (CDCl3, 30 ℃) 5.20 (ArCH2), 55.2
(-OCH3), 64.0 (-CH2OH) 70.5 (-CHOH), 72.4 (-OCH2-),
72.6 (-OCH2-), 113.8, 129.7, 130.6, 158.1.
(Comparative Example 2)
p-methoxyphenylethanol (40 mmol, 6.01 g), glycidol (20
mmol,
1.48
g), K2CO3 (0.5 mmol, 0.14 g) was stirred at 130 ° C. for 6 h. Warm hexane is added to remove unreacted substances as soluble parts, insoluble parts are distilled under reduced pressure, and α-mono p-methoxyphenylethylglyceryl ether 3- (2- (4-methoxyphenyl) -1,2-propanediol (1.10 g) was obtained.
400 MHz 1 H
NMR (CDCl 3 , 30 ° C) 2.14 (t, 1H, J = 5.1 Hz, -OH),
2.56 (d, 1H, J = 5.1 Hz, -OH), 2.83 (t, 2H, J = 6.6 Hz, -Ar-CH 2- ),
3.49 ~ 3.82 (m, 7H) 3.79 (s, 3H, -OCH 3 ), 6.84 (d, 2H, J = 8.6 Hz, Ar-H), 7.12 (d, 2H, J = 8.6 Hz, Ar-H) .
125 MHz 13 C
NMR (CDCl 3 , 30 ° C) 5.20 (ArCH 2 ), 55.2
(-OCH 3 ), 64.0 (-CH 2 OH) 70.5 (-CHOH), 72.4 (-OCH 2- ),
72.6 (-OCH 2- ), 113.8, 129.7, 130.6, 158.1.
(比較例3)
p-エトキシフェネチルアルコール (10 mmol, 1.7 g ), グリシドール (5 mmol, 380 mg ), K2CO3 (0.5 mmol, 70 mg )を130 ℃,6 h撹拌した.温ヘキサンを加え原料を取り除き,クーゲル蒸留 (200 ℃)による留出物としてα−モノp-エトキシフェニルエチルグリセリルエーテル[3-(2-(4-エトキシフェニル)-1,2-プロパンジオール)(19 %) を得た.
400 MHz 1H NMR (CDCl3,
30 ℃) 1.40 (t, 3H, J = 7.0 Hz, -CH3), 2.05 (t,
1H, J = 5.1 Hz, -OH), 2.49 (d, 1H, J = 5.1 Hz, -OH), 2.82 (t, 2H, J
= 7.0 Hz, -Ar-CH2-), 3.48~3.83 (m, 7H), 4.01 (q, 2H, J = 7.0 Hz, -CH2CH3),
6.83 (d, 2H, J = 8.1 Hz, Ar-H), 7.10 (d, 2H, J
= 8.1 Hz, Ar-H)
(Comparative Example 3)
p-Ethoxyphenethyl alcohol (10 mmol, 1.7 g), glycidol (5 mmol, 380 mg) and K2CO3 (0.5 mmol, 70 mg) were stirred at 130 ° C. for 6 h. Warm hexane was added to remove the raw material, and α-mono-p-ethoxyphenylethylglyceryl ether [3- (2- (4-ethoxyphenyl) -1,2-propanediol) as a distillate by Kugel distillation (200 ° C) ( 19%).
400 MHz 1 H NMR (CDCl 3 ,
30 ° C) 1.40 (t, 3H, J = 7.0 Hz, -CH 3 ), 2.05 (t,
1H, J = 5.1 Hz, -OH), 2.49 (d, 1H, J = 5.1 Hz, -OH), 2.82 (t, 2H, J
= 7.0 Hz, -Ar-CH 2- ), 3.48 to 3.83 (m, 7H), 4.01 (q, 2H, J = 7.0 Hz, -CH 2 CH 3 ),
6.83 (d, 2H, J = 8.1 Hz, Ar-H), 7.10 (d, 2H, J
= 8.1 Hz, Ar-H)
(実験例)
〔抗菌力(チャレンジテスト)の確認〕
合成にて得たα−モノp−ヒドロキシフェニルエチルグリセリルエーテル、α−モノp−フェニルエチルグリセリルエーテル、α−モノp−メトキシフェニルエチルグリセリルエーテル及びα−モノp−エトキシフェニルエチルグリセリルエーテルにおいて、日本薬局方保存効力試験の5菌種(S.aureus、E.coli.、Ps.aerginosa、C.arbicans、A.niger)に対する抗菌性の確認試験を行った。試料は、α−モノp−ヒドロキシフェニルエチルグリセリルエーテル、α−モノp−フェニルエチルグリセリルエーテル、α−モノp−メトキシフェニルエチルグリセリルエーテル及びα−モノp−エトキシフェニルエチルグリセリルエーテル、α−モノ2−エチルヘキシルグリセリルエーテル(SENSIVA SC-50:Schuke & Mayr社製)、モノカプリン酸グリセリル(MGK:日光ケミカルズ社製)、パラオキシ安息香酸メチル(メチルパラベン)、パラオキシ安息香酸エチル及びフェノキシエタノール(エチルパラベン)1,2−オクタンジオール(東京化成工業製)を7.0%の1,3−ブチレングリコール水溶液にそれぞれの試料配合量が0.10質量%になるように取り、試験に供した。試験菌の初期濃度はS.aureus、E.coli.、Ps.aerginosaが1×105、C.arbicans、A.nigerが10×104で行った。
(Experimental example)
[Confirmation of antibacterial activity (challenge test)]
In the α-mono p-hydroxyphenylethyl glyceryl ether, α-mono p-phenylethyl glyceryl ether, α-mono p-methoxyphenylethyl glyceryl ether and α-mono p-ethoxyphenylethyl glyceryl ether obtained by synthesis, An antibacterial confirmation test was conducted on five species of pharmacopeia preservative efficacy test (S. aureus, E. coli, Ps. Aerginosa, C. arbicans, A. niger). Samples were α-mono p-hydroxyphenyl ethyl glyceryl ether, α-mono p-phenyl ethyl glyceryl ether, α-mono p-methoxyphenyl ethyl glyceryl ether and α-mono p-ethoxyphenyl ethyl glyceryl ether, α-mono 2 -Ethylhexyl glyceryl ether (SENSIVA SC-50: manufactured by Schuke & Mayr), glyceryl monocaprate (MGK: manufactured by Nikko Chemicals), methyl paraoxybenzoate (methyl paraben), ethyl paraoxybenzoate and phenoxyethanol (ethyl paraben) 1, 2-Octanediol (manufactured by Tokyo Chemical Industry Co., Ltd.) was taken in a 7.0% 1,3-butylene glycol aqueous solution so that the amount of each sample was 0.10% by mass and subjected to the test. The initial concentration of the test bacteria is S. cerevisiae. aureus, E .; coli. , Ps. aerginosa is 1 × 10 5 , C.I. arbicans, A.M. Niger performed at 10 × 10 4 .
〔判定基準〕
1日、3日、7日、14日、28日後に各種試料より、1mLを取り出し、培養培地に加えた後、それぞれの微生物の培養条件に従い培養を行い、生菌数を確認した。表中の数値は対象菌が死滅した日を示し、菌数の表記があるものは4週間後の菌数を示している。
[Criteria]
After 1 day, 3 days, 7 days, 14 days, and 28 days, 1 mL was taken out from various samples, added to the culture medium, cultured according to the culture conditions of each microorganism, and the number of viable bacteria was confirmed. The numerical values in the table indicate the day when the target bacteria were killed, and those with the number of bacteria indicate the number of bacteria after 4 weeks.
表1は、α−モノp−ヒドロキシフェニルエチルグリセリルエーテルの類縁体の抗菌作用比較である。 Table 1 is a comparison of antibacterial activity of analogs of α-mono p-hydroxyphenylethyl glyceryl ether.
表1の結果から、P位の官能基の違いによる抗菌力の違いを確認した。その結果、p−ヒドロキシ体が極めて抗菌力が優れていることを確認した。 From the results in Table 1, the difference in antibacterial activity due to the difference in the functional group at the P position was confirmed. As a result, it was confirmed that the p-hydroxy compound was extremely excellent in antibacterial activity.
表2は、汎用抗菌剤との比較である。 Table 2 is a comparison with general-purpose antibacterial agents.
表2の結果から、α−モノp−ヒドロキシフェニルエチルグリセリルエーテルは、細菌に関しては、パラオキシ安息香酸メチル(メチルパラベン)やモノカプリン酸グリセリル(C8エステル)よりも抗菌作用は強く、エチルパラベンや2−エチルヘキシルグリセリルエーテル(C8エーテル)、1,2−オクタンタンジオール(C8ジオール)と同程度かやや強いことが分かった。また、真菌に関しては、モノカプリン酸グリセリン、2−エチルヘキシルグリセリルエーテルや1,2−オクタンジオールは増加傾向にあり効力はほとんど示さない。それに対して、死滅こそ見られないが実施例1はパラベン類と同様に初期の植菌数と比べて菌数が95.2%減少し元の4.8%と大きく減少しており、その効力は同程度であることを確認した。ここにあげたジオール構造を有する化合物は抗菌性を有することが知られているがカビに対する抗菌性が弱い。本発明のα−モノp−ヒドロキシフェニルエチルグリセリルエーテルはパラベンと置き換えることが可能であることを確認した。 From the results shown in Table 2, α-mono p-hydroxyphenylethyl glyceryl ether has a stronger antibacterial effect on bacteria than methyl paraoxybenzoate (methyl paraben) or monocaprylate glyceryl (C8 ester). It was found that it was comparable or slightly stronger than ethylhexyl glyceryl ether (C8 ether) and 1,2-octanetanediol (C8 diol). Regarding fungi, glyceryl monocaprate, 2-ethylhexyl glyceryl ether, and 1,2-octanediol tend to increase and show little efficacy. On the other hand, although death is not seen, in Example 1, as in the case of parabens, the number of bacteria decreased by 95.2% compared to the initial number of inoculations and greatly decreased to 4.8% of the original number. It was confirmed that the efficacy was similar. The compounds having a diol structure listed here are known to have antibacterial properties, but have a weak antibacterial property against mold. It was confirmed that α-mono p-hydroxyphenylethyl glyceryl ether of the present invention can be replaced with paraben.
「エマルジョン系における抗菌作用」
日本薬局方保存効力試験の5菌種(S.aureus、E.coli.、Ps.aerginosa 、C.arbicans、A.niger)に対する抗菌性の確認を行った。試料は、表5記載の組成乳液、実施例及び比較例をそれぞれ常法に従って調製し、試験を実施した。
"Antimicrobial activity in emulsion systems"
Antibacterial activity was confirmed against five bacterial species (S. aureus, E. coli, Ps. Aerginosa, C. arbicans, A. niger) in the Japanese Pharmacopoeia preservation efficacy test. Samples were prepared according to conventional methods, and the test was carried out for the composition emulsions described in Table 5, Examples and Comparative Examples.
表3の結果から、同濃度のモノカプリン酸グリセリル(C8エステル)、2−エチルヘキシルグリセリルエーテル(C8エーテル)や1,2−オクタンタンジオール(C8ジオール)と比較すると細菌に対して抗菌作用は強く、パラベン類とは同程度の抗菌作用を示すことを確認した。 From the results in Table 3, the antibacterial activity is strong against bacteria compared to the same concentration of glyceryl monocaprate (C8 ester), 2-ethylhexyl glyceryl ether (C8 ether) and 1,2-octanetanediol (C8 diol). It was confirmed that the antibacterial activity was comparable to that of parabens.
(実験例3)〔細胞毒性の確認〕
96Well Plateに1WellあたりHela細胞を播種し、24時間、CO2インキュベータの中で育成する。播種24時間後、試料を培地で段階的に希釈(1/2)して添加する。次いで、48時間、CO2インキュベータの中で育成し、96Well
Plateの培地を捨て、PBS(-)で洗浄し、その後、培地に10%濃度になるように新品のWST試薬(Cell
Counting Kit)を加えたものを、100μLずつ加える。それを2時間CO2インキュベータの中で反応させ、2時間後にマイクロプレートリーダーで415nmでの吸光度を測定する。
(Experimental example 3) [Confirmation of cytotoxicity]
96-well plate is seeded with Hela cells per well and grown in a CO2 incubator for 24 hours. Twenty-four hours after seeding, the sample is diluted serially (1/2) with medium and added. Next, it is grown in a CO2 incubator for 48 hours, 96 well
Discard the plate medium, wash with PBS (-), and then add a new WST reagent (Cell
100 μL each of those added with Counting Kit) is added. It is reacted for 2 hours in a CO2 incubator and after 2 hours the absorbance at 415 nm is measured with a microplate reader.
図1に示したようにメチルパラベンや2−エチルヘキシルグリセリルエーテル(C8エーテル)と比較して、細胞毒性は弱く、刺激性が低いことが期待される。 As shown in FIG. 1, it is expected that the cytotoxicity is weak and the irritation is low as compared with methylparaben and 2-ethylhexyl glyceryl ether (C8 ether).
次に本発明にかかるα−モノp−ヒドロキシフェニルエチルグリセリルエーテルを用いた具体的な製品例について説明する。 Next, specific product examples using the α-mono p-hydroxyphenylethyl glyceryl ether according to the present invention will be described.
(処方例)以下に本発明の処方例を挙げる。
<処方例1>化粧水(質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.1
グリセリン・・・5.0
ポリオキシエチレンソルビタンモノラウレート(20E.0)・・・0.5
1,3−ブチレングリコール・・・5.0
1,2−ペンタンジオール・・・2.0
酸化防止剤・・・適量
香料・・・適量
精製水・・・残部
(Prescription example) The following is a prescription example of the present invention.
<Prescription Example 1> Lotion (mass%)
α-mono p-hydroxyphenylethyl glyceryl ether ... 0.1
Glycerin ... 5.0
Polyoxyethylene sorbitan monolaurate (20E.0) ... 0.5
1,3-butylene glycol ... 5.0
1,2-pentanediol ... 2.0
Antioxidant ... proper amount perfume ... appropriate amount purified water ... the balance
<処方例2>化粧用クリーム (質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.1
N−ヤシ油脂肪酸アシルL−アルキ゛ンエチル−DL−ヒ゜ロリト゛ンカルホ゛ン酸塩・・0.05
ミツロウ・・・2.0
ステアリルアルコール・・・5.0
ステアリン酸・・・8.0
スクワラン・・・10.0
自己乳化型グリセリルモノステアレート・・・3.0
ポリオキシエチレンセチルエーテル(20E.0)・・・1.0
1,3−ブチレングリコール・・・5.0
グルコン酸亜鉛・・・0.1
水酸化カリウム・・・0.3
香料・・・適量
酸化防止剤・・・適量
精製水・・・残部
<Formulation example 2> Cosmetic cream (mass%)
α-mono p-hydroxyphenylethyl glyceryl ether ... 0.1
N-coconut oil fatty acid acyl L-alkenyl ethyl-DL-chlorocarbonate
Beeswax ... 2.0
Stearyl alcohol ... 5.0
Stearic acid 8.0
Squalane ... 10.0
Self-emulsifying glyceryl monostearate ... 3.0
Polyoxyethylene cetyl ether (20E.0) ... 1.0
1,3-butylene glycol ... 5.0
Zinc gluconate ... 0.1
Potassium hydroxide 0.3
Perfume ... proper amount antioxidant ... proper amount purified water ... balance
<処方例3>乳液(質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.1
N−ヤシ油脂肪酸アシルL−アルキ゛ンエチル−DL−ヒ゜ロリト゛ンカルホ゛ン酸塩・・0.05
スクワラン・・・8.0
ワセリン・・・2.0
ミツロウ・・・0.5
ソルビタンセスキオレエート・・・0.8
ポリオキシエチレンオレイルエーテル(20E.0)・・・1.2
カルボキシビニルポリマー・・・0.2
水酸化カリウム・・・0.1
1.3−ブチレングリコール・・・7.0
香料・・・適量
酸化防止剤・・・適量
精製水・・・残部
<Prescription Example 3> Emulsion (mass%)
α-mono p-hydroxyphenylethyl glyceryl ether ... 0.1
N-coconut oil fatty acid acyl L-alkenyl ethyl-DL-chlorocarbonate
Squalane ... 8.0
Petrolatum ... 2.0
Beeswax 0.5
Sorbitan sesquioleate ... 0.8
Polyoxyethylene oleyl ether (20E.0) ・ ・ ・ 1.2
Carboxyvinyl polymer ... 0.2
Potassium hydroxide ... 0.1
1.3-Butylene glycol ... 7.0
Perfume ... proper amount antioxidant ... proper amount purified water ... balance
<処方例4>パック剤(質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.5
酢酸ビニル樹脂エマルジョン・・・15.0
ポリビニルアルコール・・・10.0
ホホバ油・・・3.0
グリセリン・・・5.0
酸化チタン・・・8.0
カオリン・・・7.0
エタノール・・・5.0
香料・・・適量
酸化防止剤・・・適量
精製水・・・残部
<Prescription Example 4> Packing agent (mass%)
α-mono p-hydroxyphenylethyl glyceryl ether 0.5
Vinyl acetate resin emulsion ... 15.0
Polyvinyl alcohol ... 10.0
Jojoba oil ... 3.0
Glycerin ... 5.0
Titanium oxide ... 8.0
Kaolin 7.0
Ethanol ... 5.0
Perfume ... proper amount antioxidant ... proper amount purified water ... balance
<処方例5>軟膏(質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.2
酢酸トコフェロール・・・0.5
パラジメチルアミノ安息香酸オクチル・・・4.0
ブチルメトキシベンゾイルメタン・・・4.0
ステアリルアルコール・・・18.0
モクロウ・・・20.0
グリセリンモノステアリン酸エステル・・・0.3
ワセリン・・・33.0
香料・・・適量
酸化防止剤・・・適量
精製水・・・残部
<Prescription Example 5> Ointment (mass%)
α-mono p-hydroxyphenylethyl glyceryl ether 0.2
Tocopherol acetate ... 0.5
Octyl paradimethylaminobenzoate 4.0
Butylmethoxybenzoylmethane ... 4.0
Stearyl alcohol ... 18.0
Owl ... 20.0
Glycerin monostearate ... 0.3
Vaseline 33.0
Perfume ... proper amount antioxidant ... proper amount purified water ... balance
<処方例6>アイシャドウ(質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.2
ビサボロール・・・0.2
流動パラフィン・・・6.0
メチルポリシロキサン・・・2.0
セスキオレイン酸ソルビタン・・・2.0
タルク・・・残部
マイカ・・・15.0
セリサイト・・・5.0
顔料・・・14.5
パール顔料・・・10.0
香料・・・適量
酸化防止剤・・・適量
<Prescription Example 6> Eyeshadow (mass%)
α-mono p-hydroxyphenylethyl glyceryl ether 0.2
Bisabolol ... 0.2
Liquid paraffin 6.0
Methyl polysiloxane ... 2.0
Sorbitan sesquioleate ... 2.0
Talc ... Remaining mica ... 15.0
Sericite ... 5.0
Pigment ... 14.5
Pearl pigment ... 10.0
Perfume ... proper amount antioxidant ... proper amount
<処方例7>ドリンク剤(質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.2
タウリン・・・3.0
ピリドキシン塩酸塩・・・0.02
チアミン硫化物・・・0.01
リボフラビン・・・0.003
無水カフェイン・・・0.05
精製白糖・・・5.0
D−ソルビトール液・・・2.0
クエン酸無水物・・・0.2
香料・・・適量
精製水・・・残部
<Prescription Example 7> Drink (mass%)
α-mono p-hydroxyphenylethyl glyceryl ether 0.2
Taurine ... 3.0
Pyridoxine hydrochloride: 0.02
Thiamine sulfide ... 0.01
Riboflavin ・ ・ ・ 0.003
Anhydrous caffeine ... 0.05
Purified white sugar ... 5.0
D-sorbitol solution ... 2.0
Citric acid anhydride ... 0.2
Perfume ... appropriate amount purified water ... the balance
果汁入りゼリー(質量%)
α−モノp−ヒドロキシフェニルエチルグリセリルエーテル・・・0.1
ブドウ果汁・・・6.0
水飴・・・3.5
グラニュー糖・・・13.0
りんご酸・・・0.2
ゲル化剤 ・・・1.0
クエン酸ナトリウム・・・0.05
カラメル色素・・・0.1
香料0.2
精製水・・・残部
Jelly with fruit juice (% by mass)
α-mono p-hydroxyphenylethyl glyceryl ether ... 0.1
Grape juice ... 6.0
Minamata ... 3.5
Granulated sugar ... 13.0
Malic acid 0.2
Gelling agent ... 1.0
Sodium citrate 0.05
Caramel color ... 0.1
Fragrance 0.2
Purified water ... balance
上記した処方例1にて作成した化粧料を各化粧料について健常女性パネラー20名に2週間使用してもらい使用感触及び皮膚刺激について確認した。その結果、1名の皮膚刺激も見られず使用感触も十分に満足する回答を得た。 The cosmetics prepared in the above-mentioned Formulation Example 1 were used for 20 weeks by 20 healthy female panelists for each cosmetic, and the use feeling and skin irritation were confirmed. As a result, no skin irritation was seen by one person, and an answer that fully satisfied the feeling of use was obtained.
本発明は、抗菌剤に関し、詳しくは、パラオキシ安息香酸エステルと同等以上の優れた抗菌性を有するα−モノp−ヒドロキシフェニルエチルグリセリルエーテル及びこれを配合する化粧料、医薬品、医薬部外品や食品に関する
The present invention relates to an antibacterial agent, and more specifically, α-mono p-hydroxyphenylethyl glyceryl ether having an antibacterial property equivalent to or better than that of paraoxybenzoic acid ester, and cosmetics, pharmaceuticals, quasi drugs, About food
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009083380A JP5372573B2 (en) | 2009-03-30 | 2009-03-30 | Antibacterial agent and preparation comprising the same |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009083380A JP5372573B2 (en) | 2009-03-30 | 2009-03-30 | Antibacterial agent and preparation comprising the same |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2010235474A JP2010235474A (en) | 2010-10-21 |
JP5372573B2 true JP5372573B2 (en) | 2013-12-18 |
Family
ID=43090163
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009083380A Active JP5372573B2 (en) | 2009-03-30 | 2009-03-30 | Antibacterial agent and preparation comprising the same |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP5372573B2 (en) |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60260532A (en) * | 1984-06-07 | 1985-12-23 | Yamanouchi Pharmaceut Co Ltd | Novel catechol derivative |
US6416808B1 (en) * | 2000-09-01 | 2002-07-09 | Creagri, Inc. | Method of obtaining a hydroxytyrosol-rich composition from vegetation water |
JP4349883B2 (en) * | 2003-10-30 | 2009-10-21 | 株式会社資生堂 | Skin external composition |
JP2007039340A (en) * | 2005-07-05 | 2007-02-15 | Kanebo Cosmetics Inc | Antiseptic microbicide and external composition for skin |
JP5013753B2 (en) * | 2006-05-31 | 2012-08-29 | 株式会社マンダム | Antiseptic disinfectant composition |
-
2009
- 2009-03-30 JP JP2009083380A patent/JP5372573B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP2010235474A (en) | 2010-10-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPWO2004028520A1 (en) | Antiseptic disinfectant and cosmetics, pharmaceuticals and foods containing the antiseptic disinfectant | |
US20160271028A1 (en) | Novel use of panduratin derivatives or extract of kaempferia pandurata comprising the same | |
KR102166279B1 (en) | Composition for Anti-Oxidant, Anti-Bacterial and Anti-Inflammatory Effect Comprising Plant Complex Extracts as Active Ingredient | |
WO2006068254A1 (en) | Skin-whitening agent | |
US20230270807A1 (en) | Antimicrobial compositions | |
KR101996732B1 (en) | Cosmetic composition comprising concentrate of Omegiju fermented using magma seawater for improving wrinkles, elasticity or moisturizing the skin | |
JP6902329B2 (en) | Inhibitor of sebaceous gland cell activation | |
KR20190064714A (en) | Anti-inflammatory agent containing backhousia citriodora extract | |
KR102283527B1 (en) | Cosmetic composition comprising cereal fermented extract | |
US11306117B2 (en) | Whitening composition containing novel quercetin-based compound | |
JP2006233099A (en) | Fucoidan polysaccharide originating from discoidal phase of brown alga and its use | |
JP2010229062A (en) | Bleaching agent | |
JP5372573B2 (en) | Antibacterial agent and preparation comprising the same | |
KR101685829B1 (en) | Method for prepareing fermented extract of mistletoe having enhanced antioxidative effect | |
KR102152407B1 (en) | Cosmetic composition containing phycocyanobilin and its derivative derived from spirulina | |
KR20210044762A (en) | Anti-microbial composition comprising pinus koraiensis sieb extract | |
US20100061948A1 (en) | Composition for skin whitening comprising artemisinine | |
KR101577787B1 (en) | Composition for skin whitening comprising polyphyllin vii | |
US12097276B2 (en) | Cosmetic composition comprising theasinensin A | |
US11197878B2 (en) | Anti-inflammatory composition including novel quercetin-based compound | |
KR20180010084A (en) | Composition for moisturing skin comprising trans-3-O-galloyl-3,3',5,5',7- pentahydroxyflavan | |
KR20170130159A (en) | Composition comprising water-soluble propolis composition for preventing or treating acne | |
JP6753662B2 (en) | Anti-glycation agent | |
JP4791873B2 (en) | Antibacterial agent | |
JP2014198790A (en) | Antioxidant, cosmetics, food and drink |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120330 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130319 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130423 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130607 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130607 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130917 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130918 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5372573 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |