CN110664795A - Water-soluble composition, preparation method and application thereof - Google Patents
Water-soluble composition, preparation method and application thereof Download PDFInfo
- Publication number
- CN110664795A CN110664795A CN201910894304.XA CN201910894304A CN110664795A CN 110664795 A CN110664795 A CN 110664795A CN 201910894304 A CN201910894304 A CN 201910894304A CN 110664795 A CN110664795 A CN 110664795A
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- compound
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- independently selected
- Prior art date
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- Granted
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- 239000000203 mixture Substances 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000002537 cosmetic Substances 0.000 claims abstract description 15
- 235000013305 food Nutrition 0.000 claims abstract description 11
- 241000894006 Bacteria Species 0.000 claims abstract description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- -1 hydroxy, carboxy Chemical group 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 230000002378 acidificating effect Effects 0.000 claims description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000006683 Mannich reaction Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 241000228245 Aspergillus niger Species 0.000 claims description 5
- 241000222122 Candida albicans Species 0.000 claims description 5
- 241000588724 Escherichia coli Species 0.000 claims description 5
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 5
- 241000191967 Staphylococcus aureus Species 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229940095731 candida albicans Drugs 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims description 4
- 108010077895 Sarcosine Proteins 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- SEQVGSMAFZXDPQ-UHFFFAOYSA-N 1-[2-(ethylamino)ethoxy]ethanol Chemical compound CCNCCOC(C)O SEQVGSMAFZXDPQ-UHFFFAOYSA-N 0.000 claims description 2
- LFWVZGUDOFDLHF-UHFFFAOYSA-N 1-[2-(methylamino)ethoxy]ethanol Chemical compound CNCCOC(C)O LFWVZGUDOFDLHF-UHFFFAOYSA-N 0.000 claims description 2
- GHTDAXTYNRRXEC-UHFFFAOYSA-N 2,2-diethoxy-n-methylethanamine Chemical compound CCOC(CNC)OCC GHTDAXTYNRRXEC-UHFFFAOYSA-N 0.000 claims description 2
- HUMIEJNVCICTPJ-UHFFFAOYSA-N 2,2-dimethoxy-n-methylethanamine Chemical compound CNCC(OC)OC HUMIEJNVCICTPJ-UHFFFAOYSA-N 0.000 claims description 2
- YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 claims description 2
- 108010065338 N-ethylglycine Proteins 0.000 claims description 2
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 229940125773 compound 10 Drugs 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 claims description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- BNTDCSJFYZPOMC-UHFFFAOYSA-N n-ethyl-2,2-dimethoxyethanamine Chemical compound CCNCC(OC)OC BNTDCSJFYZPOMC-UHFFFAOYSA-N 0.000 claims description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 2
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 claims 2
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 claims 2
- 229940100595 phenylacetaldehyde Drugs 0.000 claims 1
- 150000002989 phenols Chemical class 0.000 abstract description 45
- 241001673966 Magnolia officinalis Species 0.000 abstract description 42
- 239000003755 preservative agent Substances 0.000 abstract description 21
- 241000218378 Magnolia Species 0.000 abstract description 14
- 230000002335 preservative effect Effects 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 10
- 241000233866 Fungi Species 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 4
- 241000192125 Firmicutes Species 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 26
- VVOAZFWZEDHOOU-UHFFFAOYSA-N magnolol Chemical compound OC1=CC=C(CC=C)C=C1C1=CC(CC=C)=CC=C1O VVOAZFWZEDHOOU-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 230000003385 bacteriostatic effect Effects 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 7
- 241000196324 Embryophyta Species 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- XXWFDPVOXNJASB-UHFFFAOYSA-N ethanol;phenol Chemical compound CCO.OC1=CC=CC=C1 XXWFDPVOXNJASB-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 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
- 244000005700 microbiome Species 0.000 description 4
- 229960005323 phenoxyethanol Drugs 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000008098 formaldehyde solution Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- BYTORXDZJWWIKR-UHFFFAOYSA-N Hinokiol Natural products CC(C)c1cc2CCC3C(C)(CO)C(O)CCC3(C)c2cc1O BYTORXDZJWWIKR-UHFFFAOYSA-N 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000006165 cyclic alkyl group Chemical group 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- FVYXIJYOAGAUQK-UHFFFAOYSA-N honokiol Chemical compound C1=C(CC=C)C(O)=CC=C1C1=CC(CC=C)=CC=C1O FVYXIJYOAGAUQK-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- JYOYLHDWSWWLQE-UHFFFAOYSA-N 2,2-dimethoxy-2-(methylamino)acetaldehyde Chemical compound COC(C=O)(NC)OC JYOYLHDWSWWLQE-UHFFFAOYSA-N 0.000 description 1
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 1
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 101000748141 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 32 Proteins 0.000 description 1
- 241000218377 Magnoliaceae Species 0.000 description 1
- 241001647091 Saxifraga granulata Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 102100040050 Ubiquitin carboxyl-terminal hydrolase 32 Human genes 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000006437 ethyl cyclopropyl group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000005921 isopentoxy group Chemical group 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229930013686 lignan Natural products 0.000 description 1
- 150000005692 lignans Chemical class 0.000 description 1
- 235000009408 lignans Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000003935 n-pentoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000003863 physical function Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000010267 two-fold dilution method Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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Abstract
The invention relates to the field of magnolia officinalis total phenol derivatives, and discloses a water-soluble composition which is composed of compounds with structures of a formula (1) and a formula (2). The magnolia total phenol derivative prepared by the invention has good water solubility, is colorless and transparent after being dissolved, has obvious inhibition effect on common gram-negative bacteria, gram-positive bacteria, fungi and the like, and can be used as a green natural preservative to be applied to the fields of food, medicines, cosmetics and the like.
Description
Technical Field
The invention relates to the field of magnolia officinalis total phenol derivatives, in particular to a composition of magnolia officinalis total phenol derivatives and a preparation method and application thereof.
Background
The food, the medicine and the cosmetics are rich in a large amount of water and various nutritional ingredients, a good growth environment is provided for microorganisms, and the microorganisms are difficult to invade in the production and use processes of the cosmetics, so that the cosmetics are extremely easy to decay, the quality of the products is reduced, and the health of users is threatened. The addition of the preservative into the cosmetics is an important means for protecting the products from microbial contamination, prolonging the shelf life of the products and ensuring the safety of the products.
Currently, many kinds of preservatives are used in foods, medicines and cosmetics, most of them are chemical preservatives, and dozens of them are commonly used, including acidic preservatives (benzoic acid), ester-type preservatives (parabens) and the like. However, with the development of science and the increasing awareness of safety of consumers, it is gradually found that although chemical preservatives have a good antiseptic effect, some chemical preservatives can produce adverse effects on human bodies, cause skin allergy, decrease physical functions and pollute the environment. Therefore, natural preservatives are urgently needed by various industries, and a natural preservative with low toxicity, low irritation and high performance has great significance in the fields of food, medicines, cosmetics and the like.
Cortex magnoliae officinalis (Magnolia officinalis cortex) is dried bark, root bark and branch of Magnolia officinalis linasl srehd.et wils, belonging to important traditional Chinese medicinal materials and being listed as a high-quality product in the Shennong Ben Cao Jing. Cortex Magnolia officinalis is bitter and pungent, warm in nature, and has effects in promoting qi circulation, eliminating dampness, warming middle warmer, relieving pain, lowering adverse qi, and relieving asthma. The main chemical active ingredients of the magnolia officinalis are lignans, magnolol, honokiol and the like. The phenols in cortex Magnolia officinalis have antibacterial, antitumor, analgesic, and antiinflammatory effects. But because the water solubility is poor, the mangnolia officinalis total phenols are easy to oxidize and deteriorate, and the application of the mangnolia officinalis total phenols in foods, medicines and cosmetics is greatly hindered. Generally, the general surfactants and emulsifiers can be used for solubilizing the total magnolol, in this case, the dosage of the required surfactants and emulsifiers is very large, and even if the total magnolol is applied to an aqueous formula, the total magnolol can be separated out from the aqueous formula, so that the whole system becomes white and turbid, and the use is seriously influenced. In addition, a small amount of alkali can be added into the formula system to convert the total phenols of the magnolia officinalis into salts and increase the water solubility of the total phenols of the magnolia officinalis, and the total phenols of the magnolia officinalis formed by the method are extremely unstable and easily become golden yellow, so that the conductivity of the system is increased and the bacteriostatic ability is reduced. The above method has very high requirements on the pH of a product formula system and the dosage accuracy of a thickener and an emulsifier, so that the method is basically difficult to process and apply.
The traditional method for improving the solubility of the total phenols of magnolia officinalis introduces impurity compounds into a protogen system, and the thick total phenols of magnolia officinalis are unstable after being dissolved in an aqueous solution system, so that the system is easy to deteriorate, and the bacteriostatic ability is reduced. Therefore, the modification of the structure of the total phenols of the magnolia officinalis improves the solubility and the bacteriostatic ability of the total phenols of the magnolia officinalis in water, and is a problem to be solved urgently when the total phenols of the magnolia officinalis are used as natural preservatives to be applied to foods, medicines and cosmetics.
Disclosure of Invention
The invention aims to solve the problems of poor water solubility of the total phenols of magnolia officinalis and reduced bacteriostatic ability after the total phenols of magnolia officinalis are dissolved in an aqueous solution system, and provides a composition of the total phenols of magnolia officinalis and a preparation method and application thereof. The water-soluble magnolia total phenol derivative provided by the invention has excellent stability and bacteriostatic ability when being applied to a preservative.
In order to achieve the above object, in a first aspect, the present invention provides a water-soluble composition consisting of a compound having a structure of formula (1) and a compound having a structure of formula (2):
wherein the content of the compound with the structure of the formula (1) in the water-soluble composition is 20-80 wt%.
According to the invention, in the formulae (1) and (2), R1、R2、R3And R4Each independently selected from hydrogen, halogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C1-C12Alkoxy, substituted or unsubstituted C6-C10Aryl group of (1).
Preferably, R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from halogen, C1-C6Alkoxy and C6-C10Aryl group of (1).
Preferably, R1、R2、R3And R4Each independently is substituted or unsubstituted C1-C10Alkyl group of (1).
Preferably, R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C6Alkoxy of the general formula-O-R9-a radical of the OH structure.
Wherein R is9Is C1-C6An alkylene group of (a).
Preferably, R5、R6、R7And R8Each independently selected from hydrogen and C6-C10Aryl and C1-C6Alkyl group of (1).
In a second aspect, the present invention provides a method for preparing a water-soluble composition, which comprises first contacting a compound having a structure of formula (3) and/or (4) with a compound having a structure of formula (5) and/or (6) under Mannich reaction conditions, and then second contacting the product of the first contacting with a composition consisting of a compound having a structure of formula (7) and a compound having a structure of formula (8) to obtain a Mannich reaction product.
Wherein the content of the compound with the structure of the formula (1) in the water-soluble composition is 20-80 wt%.
Preferably, in formula (3) and formula (5), R1、R2、R3And R4Each independently is substituted or unsubstituted C1-C10Alkyl group of (1).
Preferably, R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C6Alkoxy of the general formula-O-R9-a radical of the OH structure.
Wherein R is9Is C1-C6An alkylene group of (a).
Preferably, in formula (4) and formula (6), R5、R6、R7And R8Each independently selected from hydrogen and C6-C10Aryl and C1-C6Alkyl group of (1).
Preferably, in formula (7) and formula (8), R1、R2、R3And R4Each independently selected from hydrogen, halogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C1-C12Alkoxy, substituted or unsubstituted C6-C10Aryl group of (1).
Preferably, R1、R2、R3And R4Optionally toThe substituents present are each independently selected from halogen, C1-C6Alkoxy and C6-C10Aryl group of (1).
In a third aspect, the invention provides the use of the water-soluble composition in bacteriostasis.
The modified magnolia officinalis total phenol derivative which can be used for bacteriostasis is prepared by modifying the structure of the magnolia officinalis total phenol, has good water solubility, is colorless and transparent after being dissolved, has obvious inhibition effect on common gram-negative bacteria, gram-positive bacteria, fungi and the like, and can be used as a green and natural preservative to be applied to the fields of food, medicines, cosmetics and the like.
Additional features and advantages of the invention will be set forth in the detailed description which follows.
Detailed Description
The following is a detailed description of specific embodiments of the present invention. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
Some of the terms referred to in this aspect are explained below:
“C1-C10the "alkyl group" of (a) represents an alkyl group having 1 to 10 carbon atoms in total, and includes a straight-chain alkyl group, a branched-chain alkyl group or a cyclic alkyl group, and specifically may be a straight-chain alkyl group, a branched-chain alkyl group or a cyclic alkyl group having 1, 2,3, 4, 5, 6, 7, 8, 9, 10 carbon atoms in total, and may be, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a n-hexyl group, a,Methylcyclopropyl, ethylcyclopropyl, cyclopentyl, methylcyclopentyl, cyclohexyl, and the like.
“C1-C12The "alkoxy group" of (b) represents an alkoxy group having 1 to 12 carbon atoms in total, and includes a linear alkoxy group, a branched alkoxy group and a cycloalkoxy group, and specifically may be a linear alkoxy group, a branched alkoxy group or a cycloalkoxy group having 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12 carbon atoms in total, and may be, for example, a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a t-butoxy group, a n-pentoxy group, an isopentoxy group, a n-hexoxy group, a n-heptoxy group, a n-octoxy group, a n-nonoxy group, a n-decoxy group, a cyclopropoxy group, a methyl cyclopropoxy.
“C6-C10The "aryl group" of (a) represents an aryl group having 6 to 10 carbon atoms in total, at least one H group being substituted by C on the benzene ring of the aryl group1-C4And alkyl group of (a) is substituted, for example, tolyl, ethylphenyl, n-propylphenyl, isopropylphenyl, n-butylphenyl, orthoxylyl, m-xylyl, p-xylyl, etc.
Other similar groups are defined herein with reference to the foregoing definitions, only with respect to the number of carbon atoms or the manner of isomerisation.
In a first aspect, the present invention provides a water-soluble composition consisting of a compound having the structure of formula (1) and a compound having the structure of formula (2):
wherein the content of the compound with the structure of the formula (1) in the water-soluble composition is 20-80 wt%.
Preferably, in formula (1) and formula (2), R1、R2、R3And R4Each independently selected from hydrogen, halogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C1-C12Alkoxy, substituted or unsubstituted C6-C10Aryl group of (1).
Preferably, R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from halogen, C1-C6Alkoxy and C6-C10Aryl group of (1).
Preferably, R1、R2、R3And R4Each independently is substituted or unsubstituted C1-C10Alkyl group of (1).
Preferably, R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C6Alkoxy of the general formula-O-R9-a radical of the OH structure.
Wherein R is9Is C1-C6An alkylene group of (a).
Preferably, R5、R6、R7And R8Each independently selected from hydrogen and C6-C10Aryl and C1-C6Alkyl group of (1).
According to a preferred embodiment of the present invention, wherein, in the formulae (1) and (2), R1、R2、R3And R4Each independently selected from hydrogen, fluorine, chlorine, bromine, substituted or unsubstituted C1-C5Alkyl, substituted or unsubstituted C1-C6Alkoxy, substituted or unsubstituted C6-C8Aryl group of (1).
Preferably, R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from fluorine, chlorine, bromine, C1-C3Alkoxy and C6-C8Aryl group of (1).
R1、R2、R3And R4Each independently is substituted or unsubstituted C1-C5Alkyl group of (1).
R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C3Alkoxy group of,The general formula is-O-R9-a radical of the OH structure.
Wherein R is9Is C1-C3An alkylene group of (a).
Preferably, R1、R2、R3And R4Each independently of the other being methyl, 
R5、R6、R7And R8Each independently selected from hydrogen and C6-C8Aryl and C1-C3Alkyl groups of (a);
preferably, in formula (1) and formula (2), R5、R6、R7And R8Are all hydrogen.
According to a preferred embodiment of the present invention, in the water-soluble composition, the compound having the structure of formula (1) is selected from at least one of the following compounds:
compound 1:
compound 2:
compound 3:
compound 4:
compound 5:
wherein the compound with the structure of the formula (2) is selected from at least one of the following compounds:
compound 6:
compound 7:
compound 8:
compound 9:
compound 10:
the inventor of the invention finds that the composition of the magnolia total phenol derivative in the preferred embodiment has more excellent water solubility and bacteriostatic ability.
In a second aspect, the present invention provides a method for preparing a water-soluble composition, which comprises first contacting a compound having a structure of formula (3) and/or (4) with a compound having a structure of formula (5) and/or (6) under Mannich reaction conditions, and then second contacting the product of the first contacting with a composition consisting of a compound having a structure of formula (7) and a compound having a structure of formula (8) to obtain a Mannich reaction product.
Wherein the content of the compound with the structure of the formula (1) in the water-soluble composition is 20-80 wt%.
Preferably, in formula (3) and formula (5), R1、R2、R3And R4Each independently is substituted or unsubstituted C1-C10Alkyl group of (1).
R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C6Alkoxy of the general formula-O-R9-a radical of the OH structure.
Wherein R is9Is C1-C6An alkylene group of (a).
Preferably, in formula (4) and formula (6), R5、R6、R7And R8Each independently selected from hydrogen and C6-C10Aryl and C1-C6Alkyl group of (1).
Preferably, in formula (7) and formula (8), R1、R2、R3And R4Each independently selected from hydrogen, halogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C1-C12Alkoxy, substituted or unsubstituted C6-C10Aryl group of (1).
R1、R2、R3And R4Each of the substituents optionally present on (A) is independently selected from halogen, C1-C6Alkoxy and C6-C10Aryl group of (1).
According to the present invention, the compound having the structure of formula (3) and/or formula (5) is an amine compound, and the amine is not particularly limited in the present invention, and may be a linear alkylamine, a branched alkylamine, a cycloalkylamine, a hydroxyalkylamine, or various amino acids, and preferably a secondary amine thereof, and the secondary amine is not particularly limited in the present invention, and preferably is at least one of N-methyl-glycine, N-ethyl-glycine, N-methyl-aminoethoxyethanol, N-ethyl-aminoethoxyethanol, methylaminoacetaldehyde dimethyl acetal, methylaminoacetaldehyde diethyl acetal, ethylaminoacetaldehyde dimethyl acetal, diethanolamine, dimethylamine, diethylamine, and di-N-propylamine.
Preferably, the molar ratio of the total amount of the compound having the structure of formula (2) and/or formula (4), the total amount of the compound having the structure of formula (4) and/or formula (6), and the composition consisting of the compounds having the structures of formula (7) and formula (8) is 0.5 to 6: 0.5-6: 1, preferably 1 to 4: 1-4: 1.
preferably, the compound having the structure of formula (4) and/or formula (6) is an aldehyde compound, and the aldehyde compound is not particularly limited in the present invention, and for example, the aldehyde selected may be at least one of formaldehyde, acetaldehyde, propionaldehyde, and benzaldehyde, and is preferably formaldehyde.
According to a preferred embodiment of the present invention, the first and second contacting are carried out in the presence of an acidic substance and a solvent, wherein the solvent is water and/or an organic solvent. The acidic substance is not particularly limited, and may be at least one of hydrochloric acid, sulfuric acid, phosphoric acid, or acetic acid.
According to a preferred embodiment of the present invention, the first and second contacting are carried out in the presence of water and/or an organic solvent, which is not particularly limited in the present invention and may be conventionally selected in the art, preferably a polar organic solvent, further preferably a polar solvent containing a hydroxyl group or a carbonyl group, for example, the organic solvent is preferably selected from methanol, ethanol and acetic acid, preferably methanol and/or ethanol.
According to a preferred embodiment of the present invention, the method for preparing the composition of the magnolia total phenol derivative comprises the steps of mixing the compound having the structure of formula (3) and/or formula (5) with the compound having the structure of formula (4) and/or formula (6) under Mannich reaction conditions for first contact, and then carrying out second contact on the product obtained by the first contact and the composition of the compound having the structure of formula (7) and the compound having the structure of formula (8). In the first contact, the aldehyde compound is first contacted with the secondary amine compound at a temperature of 20 to 50 deg.C, preferably 30 to 40 deg.C, for 5 to 20min, preferably 10 to 15 min. The aldehyde compound may be in the form of a solution, and the solvent of the solution is water. Subsequently, the first contacted system is placed in a low-temperature water bath, the acidic substance or the solution of the acidic substance in the organic solvent is added into the system, the temperature is controlled to be 1-10 ℃, preferably 2-5 ℃, and the continuous contact time is 0.5-2h, preferably 0.6-1.5 h. In the present invention, the timing of adding the acidic substance is not particularly limited, and the acid may be added at the same time as the first contact, and preferably, the acid is added to the organic solvent first and then added together with the organic solvent. The inventors of the present invention have found that the above preferred mode is effective in reducing acid mist and avoiding the side reaction due to the exothermic heat of reaction, as compared with the mode in which the acid is directly added to the reactants. The low-temperature water bath is not particularly limited, and may be selected conventionally in the field, and is preferably an ice salt bath, and the salt in the ice salt bath is not particularly limited, and is preferably at least one of potassium chloride, sodium sulfate, and potassium sulfate. In the ice salt bath, the amount of the salt is 0.5 to 5 wt% based on the weight of water.
Preferably, the second contacting is carried out at a temperature of from 30 to 90 deg.C, preferably from 70 to 85 deg.C, for a period of from 1 to 3 hours, preferably from 1.5 to 2 hours.
According to the present invention, preferably, the method further comprises: the product of the second contact of step (ii) is evaporated and purified in sequence. The evaporation operation is not particularly limited in the invention and can be selected conventionally in the field, and the invention adopts a rotary evaporator to evaporate and remove most of the organic solvent; the purification operation is not particularly limited in the present invention, and may be a conventional operation in the field, preferably purification is performed by column chromatography, the purification packing is 100-200 mesh silica gel, the eluent is not particularly limited and may be a conventional choice in the field, preferably, the eluent is ethyl acetate/acetone, and the volume ratio of ethyl acetate and acetone is preferably 2-6:1, and particularly preferably 4: 1.
According to the invention, preferably, the compound with the structure of the formula (7) and the compound with the structure of the formula (8) are both from plant extracts, the plant in the invention is magnolia officinalis belonging to magnoliaceae, and the content of the composition of the compound with the structure of the formula (7) and the compound with the structure of the formula (8) in the extracts is more than or equal to 80%.
In a third aspect, the invention also provides an application of the water-soluble composition in bacteriostasis.
The magnolia total phenol derivative provided by the invention can be applied to food, medicine and cosmetics, can be used as a preservative or a preservative component, and has an inhibiting effect on common escherichia coli, staphylococcus aureus, pseudomonas aeruginosa, candida albicans, aspergillus niger and the like. The total phenol derivative of Magnolia officinalis is used in an amount of 0.001-0.01 g per gram of the food, medicine or cosmetic.
The present invention will be described in detail below by way of examples. In the following examples, the molecular structure of the prepared magnolia total phenol derivative is measured by a flight time mass spectrometer, a nuclear magnetic resonance spectrometer and a liquid chromatography mass spectrometer, wherein the flight mass spectrometer is of the type HR EI-TOFMS and is purchased from Kore company in UK; the model of the nmr spectrometer was semer femospin 80, purchased from semer femtole corporation; the model of the liquid chromatography-mass spectrometer is a TSQ Altis triple quadrupole mass spectrometer purchased from Saimer Fei company; the content of the plant-derived magnolia officinalis total phenols is 70%, 80% and 90%, and the magnolia officinalis total phenols are purchased from Hainan Jiamu Biotechnology limited; the N-methyl-glycine powder and N-methyl-aminoglyoxal dimethyl acetal are purchased from Shanghai Merlin biological reagents, Inc.; the nutrient broth is purchased from Beijing Meiruida science and technology Limited and mainly comprises peptone, beef extract, sodium chloride and water; the Sa's medium is purchased from Shandong West Asia chemical industry Co., Ltd, and contains peptone and agar as main ingredients; TTC is short for 2,3, 5-triphenyltetrazolium chloride, and the used TTC reagent is purchased from Shanghai leaf Biotech limited; nipagin methyl ester is analytically pure and purchased from Shanghai Michelin Biochemical technology, Inc.; phenoxyethanol was analytically pure and purchased from Shanghai Aladdin Biotechnology GmbH.
Example 1
1ml of hydrochloric acid with the concentration of 12mol/L is added into 70ml of methanol to prepare methanolic acid solution for later use. Weighing 7.6g of N-methyl-glycine powder, putting the powder into a three-neck flask, slowly dropwise adding 10ml of 37% formaldehyde solution, magnetically stirring, controlling the dropwise adding speed to be 1ml/min and controlling the temperature to be 30-35 ℃. Under the condition of ice-water bath, 40ml of prepared methanolic acid solution is added into a three-neck flask, the dropping speed is controlled to be 4ml/min, the temperature is controlled to be 2-5 ℃, and magnetic stirring is continued for 1 hour. 13.3g of plant-derived Magnolia officinalis total phenols (70% content) was weighed out and dissolved in the remaining 30ml of methanolic acid solution. Putting the three-neck flask in an oil bath, controlling the temperature to be 85 ℃, adding a methanolic acid solution of the total phenols of the mangnolia officinalis, condensing and refluxing, and reacting for 12 hours. Removing excessive methanol by using a rotary evaporator, purifying by using a 200-mesh silica gel column, eluting with ethyl acetate/acetone at a volume ratio of 4:1, combining the eluates, concentrating, and freeze-drying to obtain the Magnolia officinalis total phenol derivative. The yield is 35 percent based on the total phenols of the magnolia officinalis in the reaction raw materials. The general magnolol derivative is characterized by using flight mass spectrum and nuclear magnetic resonance, and is proved to be the general magnolol derivative with the structure shown in the formula (1) and the formula (2). The mechanism of the reaction is as follows:
example 2
1ml of hydrochloric acid with the concentration of 12mol/L is added into 70ml of methanol to prepare methanolic acid solution for later use. Weighing 11.3g of 40% dimethylamine solution, putting the dimethylamine solution into a three-neck flask, slowly dripping 10ml of 37% formaldehyde solution, magnetically stirring, controlling the dripping speed to be 1ml/min and controlling the temperature to be 30-35 ℃. Under the condition of ice-water bath, 40ml of prepared methanolic acid solution is added into a three-neck flask, the dropping speed is controlled to be 4ml/min, the temperature is controlled to be 2-5 ℃, and magnetic stirring is continued for 1 hour. 13.3g of plant-derived Magnolia officinalis total phenols (80% content) was weighed out and dissolved in the remaining 30ml of methanolic acid solution. Putting the three-neck flask in an oil bath, controlling the temperature to be 75 ℃, adding a methanol solution of the total magnolol, condensing and refluxing, and reacting for 6 hours. Removing excessive methanol by using a rotary evaporator, purifying by using a 200-mesh silica gel column, eluting with ethyl acetate/acetone at a volume ratio of 4:1, combining the eluates, concentrating, and freeze-drying to obtain the Magnolia officinalis total phenol derivative. The yield is 74 percent based on the total phenols of the magnolia officinalis in the reaction raw materials. The general magnolol derivative is characterized by using flight mass spectrum and nuclear magnetic resonance, and is proved to be the general magnolol derivative with the structure shown in the formula (1) and the formula (2). The mechanism of the reaction is as follows:
example 3
1ml of hydrochloric acid with the concentration of 12mol/L is added into 70ml of methanol to prepare methanolic acid solution for later use. Weighing 13g of diethanolamine, putting the diethanolamine into a three-neck flask, slowly dropwise adding 10ml of 37% formaldehyde solution, magnetically stirring, controlling the dropwise adding speed to be 1ml/min, and controlling the temperature to be 30-35 ℃. In an ice-water bath, 40ml of prepared methanolic acid solution is added into a three-neck flask, the dropping speed is controlled to be 4ml/min, the temperature is controlled to be 2-5 ℃, and magnetic stirring is continued for 1 h. Weighing 10g of plant-derived total phenols (content: 90%), and dissolving in the rest 30ml of methanol acid solution. Putting the three-neck flask in an oil bath, controlling the temperature to be 70 ℃, adding a methanol solution of the total magnolol, condensing and refluxing, and reacting for 6.5 hours. Removing excessive methanol by using a rotary evaporator, purifying by using a 200-mesh silica gel column, eluting with ethyl acetate/acetone at a volume ratio of 4:1, combining the eluates, concentrating, and freeze-drying to obtain the Magnolia officinalis total phenol derivative. The yield is 92 percent based on the total phenols of the magnolia officinalis in the reaction raw materials. The general magnolol derivative is characterized by using flight mass spectrum and nuclear magnetic resonance, and is proved to be the general magnolol derivative with the structure shown in the formula (1) and the formula (2). The mechanism of the reaction is as follows:
test example 1
The solubility test method is as follows: a measuring cylinder is used to measure 25 +/-1 ℃ and 100g of deionized water, and the deionized water is put into a 250ml beaker. Put into a magnetic stirrer, and the rotating speed is adjusted to be 200 rmp/min. The samples from examples 1, 2 and 3 were weighed on an analytical balance and dissolved in deionized water in an amount of 0.1g each time until complete dissolution was not achieved after stirring for 10 minutes, and the maximum dissolved mass was recorded. The results are shown in Table 1.
Test example 2
The sample of the magnolia total phenol derivative prepared in the example 3 is used as a test object, and the minimum inhibitory concentration MIC value of the sample is quantitatively tested. A10% Magnolia bark total phenolic ethanol solution, methyl paraben, a traditional chemical preservative, and phenoxyethanol were used as comparative examples.
The test method of the MIC value of the minimum inhibitory concentration comprises the following steps: the sterilized nutrient broth (used for culturing escherichia coli, staphylococcus aureus and pseudomonas aeruginosa) and the saxifrage medium (used for culturing candida albicans and aspergillus niger) are used as diluents, test samples are diluted by a two-fold dilution method, and then the bacteria are inoculated according to the concentrations shown in table 2. Culturing the bacteria at 35 deg.C for 36 h; the fungus was cultured at 28 ℃ for 48 h. And adding a TTC reagent 3h before the end point of the culture, continuing the culture, if the culture solution turns red, determining that the concentration cannot inhibit the growth of the microorganism, and if the culture solution does not turn red, determining that the minimum medicament concentration in the culture solution which does not turn red is the minimum bacteriostatic concentration of the bacteriostatic agent on the microorganism. The specific results are shown in Table 3.
Test example 3
The magnolia total phenol derivative prepared in example 3 was added to the spray formulation as shown in table 4 below. Inoculating certain amount of bacteria and fungi, and detecting microbial quantity change at intervals of 0 day, 7 days, 14 days, 21 days and 28 days according to the detection method of the microbial preservative efficacy test of United states Pharmacopeia USP32<51 >. The results are shown in Table 5 below.
TABLE 1
| Quality of dissolution | Cortex Magnolia officinalis Total phenols | Example 1 | Example 2 | Example 3 |
| Solvent water (100g) | -- | ＞3g | ＞1g | ＞10g |
Note: - -means that 0.1g is not completely dissolved; indicates that the sample is totally dissolved
TABLE 2
TABLE 3
| MIC(％) | Example 3 | 10% Magnolia officinalis total phenol ethanol solution | Nipagin methyl ester | Phenoxyethanol |
| Escherichia coli | 0.032 | 1.36 | 0.156 | 0.25 |
| Staphylococcus aureus | 0.032 | 0.0049 | 0.078 | 0.125 |
| Pseudomonas aeruginosa | 0.125 | 1.32 | 1.25 | 1 |
| Candida albicans | 0.062 | 0.0065 | 0.626 | 0.25 |
| Aspergillus niger | 0.125 | 0.0063 | 0.626 | 0.5 |
TABLE 4
TABLE 5
As can be seen from the results in Table 1, in the solubility qualitative test, the solubility of the magnolia officinalis total phenol derivative prepared by the invention in 100g of solvent water is more than 1g, namely, the sample prepared in the example is completely dissolved, while the magnolia officinalis total phenol extracted from the plant is not soluble in water; the data in table 3 show that the magnolia total phenol derivative prepared in example 3 has significant bacteriostatic action on escherichia coli, staphylococcus aureus, pseudomonas aeruginosa, candida albicans and aspergillus niger, and the bacteriostatic effect is superior to that of the traditional chemical preservatives, namely methyl paraben and phenoxyethanol; the spray formulation of table 4 provides a very suitable environment for the survival of bacteria and fungi and it can be seen from the data in table 5 that under such harsh conditions the sample prepared in example 3 of the present invention exhibited excellent bacteriostatic ability, as tested by the preservative challenge test for the 28 day water formulation spray, and the magnolia total phenol derivative in example 3 passed the preservative challenge test as a preservative.
Because the total phenol of the magnolia officinalis is not dissolved in water, the bacteriostatic effect is difficult to test. The 10% magnolia total phenol ethanol solution has a good bacteriostatic effect, but the national standard strictly limits the dosage of ethanol in cosmetics, and when the magnolia total phenol ethanol solution is applied to a water system, magnolol and honokiol can be separated out from ethanol, so that the magnolia total phenol ethanol solution cannot be applied industrially.
The magnolia officinalis total phenol derivative obtained by modifying the magnolia officinalis total phenol by adopting the method has good water solubility, and the solubility of the magnolia officinalis total phenol in water is effectively improved; the magnolia total phenol derivative has obvious inhibiting effect on common gram-negative bacteria, gram-positive bacteria, fungi and the like.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.
Claims (10)
1. A water-soluble composition consisting of a compound having the structure of formula (1) and a compound having the structure of formula (2):
wherein the content of the compound with the structure of the formula (1) in the water-soluble composition is 20-80 wt%;
in the formulae (1) and (2), R1、R2、R3And R4Each independently selected from hydrogen, halogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C1-C12Alkoxy, substituted or unsubstituted C6-C10Aryl of (a);
R1、R2、R3and R4Each of the substituents optionally present on (A) is independently selected from halogen, C1-C6Alkoxy and C6-C10Aryl of (a);
R1、R2、R3and R4Each independently is substituted or unsubstituted C1-C10Alkyl groups of (a);
R1、R2、R3and R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C6Alkoxy of the general formula-O-R9-a group of OH structure;
wherein R is9Is C1-C6An alkylene group of (a);
R5、R6、R7and R8Each independently selected from hydrogen and C6-C10Aryl and C1-C6Alkyl group of (1).
2. The water-soluble composition of claim 1, which isIn the formulae (1) and (2), R1、R2、R3And R4Each independently selected from hydrogen, fluorine, chlorine, bromine, substituted or unsubstituted C1-C5Alkyl, substituted or unsubstituted C1-C6Alkoxy, substituted or unsubstituted C6-C8Aryl of (a);
R1、R2、R3and R4Each of the substituents optionally present on (A) is independently selected from fluorine, chlorine, bromine, C1-C3Alkoxy and C6-C8Aryl of (a);
R1、R2、R3and R4Each independently is substituted or unsubstituted C1-C5Alkyl groups of (a);
R1、R2、R3and R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C3Alkoxy of the general formula-O-R9-a group of OH structure;
wherein R is9Is C1-C3An alkylene group of (a);
R5、R6、R7and R8Each independently selected from hydrogen and C6-C8Aryl and C1-C3Alkyl groups of (a);
preferably, in formula (1) and formula (2), R5、R6、R7And R8Are all hydrogen.
3. The water-soluble composition according to claim 1 or 2, wherein the compound having the structure of formula (1) is selected from at least one of the following compounds:
compound 1:
compound 2:
compound 3:
compound 4:
compound 5:
wherein the compound with the structure of the formula (2) is selected from at least one of the following compounds:
compound 6:
compound 7:
compound 8:
compound 9:
compound 10:
4. a method for preparing a water-soluble composition, which is characterized by comprising the steps of carrying out first contact on a compound with a structure shown in a formula (3) and/or a formula (4) and a compound with a structure shown in a formula (5) and/or a formula (6) under Mannich reaction conditions, and then carrying out second contact on a product obtained by the first contact and a composition consisting of the compound with a structure shown in a formula (7) and the compound with a structure shown in a formula (8) to obtain a Mannich reaction product;
wherein the content of the compound represented by the formula (7) and the content of the compound represented by the formula (8) in the composition are not zero;
R1、R2、R3and R4Each independently is substituted or unsubstituted C1-C10Alkyl groups of (a);
R1、R2、R3and R4Each of the substituents optionally present on (A) is independently selected from hydroxy, carboxy, C1-C6Alkoxy of the general formula-O-R9-a group of OH structure;
wherein R is9Is C1-C6An alkylene group of (a);
R5、R6、R7and R8Each independently selected from hydrogen and C6-C10Aryl and C1-C6Alkyl groups of (a);
in the formulae (7) and (8), R1、R2、R3And R4Each independently selected from hydrogen, halogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C1-C12Alkoxy, substituted or unsubstituted C6-C10Aryl of (a);
R1、R2、R3and R4Each of the substituents optionally present on (A) is independently selected from halogen, C1-C6Alkoxy and C6-C10Aryl group of (1).
5. The method according to claim 4, wherein the compound having the structure of formula (3) and/or formula (5) is selected from at least one of N-methyl-glycine, N-ethyl-glycine, N-methyl-aminoethoxyethanol, N-ethyl-aminoethoxyethanol, methylaminoacetaldehyde dimethyl acetal, methylaminoacetaldehyde diethyl acetal, ethylaminoacetaldehyde dimethyl acetal, diethanolamine, dimethylamine, diethylamine, di-N-propylamine;
the molar ratio of the total amount of the compound having the structure of formula (3) and/or formula (5), the total amount of the compound having the structure of formula (4) and/or formula (6) to the composition consisting of the compounds having the structures of formula (7) and formula (8) is 0.5 to 6: 0.5-6: 1, preferably 1 to 4: 1-4: 1.
6. the method according to claim 4, wherein the compound having the structure of formula (4) and/or formula (6) is at least one selected from formaldehyde, acetaldehyde, propionaldehyde, benzaldehyde, phenylacetaldehyde, o-methyl benzaldehyde, and preferably formaldehyde.
7. The method of claim 4, wherein the first and second contacting are both performed in the presence of water and/or an organic solvent, and in acidic conditions provided by at least one of hydrochloric acid, phosphoric acid, sulfuric acid, and acetic acid;
preferably, the organic solvent is selected from at least one of methanol, ethanol and acetic acid, preferably methanol and/or ethanol.
8. The method of claim 7, wherein the first contacting comprises adding the compound having the structure of formula (4) and/or formula (6) to the compound having the structure of formula (3) and/or formula (5) at 20-50 ℃, then adding the acidic substance or the solution of the acidic substance in the solvent at 1-10 ℃, and continuing the reaction for 0.5-2 h;
preferably, the second contacting mode comprises dissolving the compounds with the structures of the formula (7) and the formula (8) in the solvent in the presence of an acidic substance to form a solution, and then carrying out the second contacting with the product obtained by the first contacting.
9. Use of a water-soluble composition according to any one of claims 1 to 3 for bacteriostasis.
10. The use according to claim 9, wherein the bacteria are selected from at least one of escherichia coli, staphylococcus aureus, pseudomonas aeruginosa, candida albicans, aspergillus niger; preferably, the bacteria are present in the food, pharmaceutical or cosmetic product in an amount of 0.001-0.01 gram per gram of the food, pharmaceutical or cosmetic product.
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| WO2021052269A1 (en) * | 2019-09-20 | 2021-03-25 | 广东省禾基生物科技有限公司 | Water-soluble composition, preparation method and application thereof |
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