WO2013073642A1 - 還元型ピロロキノリンキノンのゲル - Google Patents
還元型ピロロキノリンキノンのゲル Download PDFInfo
- Publication number
- WO2013073642A1 WO2013073642A1 PCT/JP2012/079709 JP2012079709W WO2013073642A1 WO 2013073642 A1 WO2013073642 A1 WO 2013073642A1 JP 2012079709 W JP2012079709 W JP 2012079709W WO 2013073642 A1 WO2013073642 A1 WO 2013073642A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- gel
- salt
- group
- pyrroloquinoline quinone
- pqq
- Prior art date
Links
- QZMUBZJJJKIXKV-UHFFFAOYSA-N pyrroloquinoline quinol Chemical compound N1=C(C(O)=O)C=C(C(O)=O)C2=C(NC(C(=O)O)=C3)C3=C(O)C(O)=C21 QZMUBZJJJKIXKV-UHFFFAOYSA-N 0.000 title claims abstract description 34
- MMXZSJMASHPLLR-UHFFFAOYSA-N pyrroloquinoline quinone Chemical class C12=C(C(O)=O)C=C(C(O)=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 MMXZSJMASHPLLR-UHFFFAOYSA-N 0.000 claims abstract description 205
- 150000003839 salts Chemical class 0.000 claims abstract description 95
- 239000002612 dispersion medium Substances 0.000 claims abstract description 53
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 35
- 238000002156 mixing Methods 0.000 claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 15
- 235000013305 food Nutrition 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 239000003349 gelling agent Substances 0.000 claims description 12
- 239000002537 cosmetic Substances 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 10
- 229920000642 polymer Polymers 0.000 claims description 9
- 239000000499 gel Substances 0.000 description 131
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 56
- 239000000243 solution Substances 0.000 description 45
- 229960005070 ascorbic acid Drugs 0.000 description 35
- 239000011668 ascorbic acid Substances 0.000 description 34
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 28
- 235000010323 ascorbic acid Nutrition 0.000 description 27
- -1 i -Pentyl Chemical group 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 239000000523 sample Substances 0.000 description 15
- 238000001879 gelation Methods 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000000835 fiber Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- XYVQFUJDGOBPQI-UHFFFAOYSA-N Methyl-2-hydoxyisobutyric acid Chemical compound COC(=O)C(C)(C)O XYVQFUJDGOBPQI-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 229920001817 Agar Polymers 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 5
- 239000004793 Polystyrene Substances 0.000 description 5
- 238000011481 absorbance measurement Methods 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- 235000010419 agar Nutrition 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 229920001155 polypropylene Polymers 0.000 description 5
- 229920002223 polystyrene Polymers 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 159000000000 sodium salts Chemical group 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000002211 ultraviolet spectrum Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 4
- 238000000879 optical micrograph Methods 0.000 description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 4
- DITJMKNNGYPPQD-UHFFFAOYSA-N 4,5-dioxo-1h-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid;sodium Chemical compound [Na].C12=C(C(O)=O)C=C(C(O)=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 DITJMKNNGYPPQD-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 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 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 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 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-isoascorbic acid Chemical compound OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 235000019484 Rapeseed oil Nutrition 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- 229940116333 ethyl lactate Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 235000003969 glutathione Nutrition 0.000 description 2
- 239000001087 glyceryl triacetate Substances 0.000 description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 229940052665 nadh Drugs 0.000 description 2
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000014593 oils and fats Nutrition 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 125000004344 phenylpropyl group Chemical group 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 2
- 229960002622 triacetin Drugs 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- LGBPWIAXPVUTMY-JLAZNSOCSA-N (2r)-3,4-dihydroxy-2-[(1s)-1-hydroxyethyl]-2h-furan-5-one Chemical compound C[C@H](O)[C@H]1OC(=O)C(O)=C1O LGBPWIAXPVUTMY-JLAZNSOCSA-N 0.000 description 1
- ILBBPBRROBHKQL-SAMGZKJBSA-N (2s)-3,4-dihydroxy-2-[(1r,2r)-1,2,3-trihydroxypropyl]-2h-furan-5-one Chemical compound OC[C@@H](O)[C@@H](O)[C@@H]1OC(=O)C(O)=C1O ILBBPBRROBHKQL-SAMGZKJBSA-N 0.000 description 1
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 1
- 0 *c1cc(C(C(c2nc(*)cc(*)c2-2)=O)=O)c-2[n]1 Chemical compound *c1cc(C(C(c2nc(*)cc(*)c2-2)=O)=O)c-2[n]1 0.000 description 1
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 244000247812 Amorphophallus rivieri Species 0.000 description 1
- 235000001206 Amorphophallus rivieri Nutrition 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 229920000855 Fucoidan Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- 229920002581 Glucomannan Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- PSJQCAMBOYBQEU-UHFFFAOYSA-N Glyoxalase I Natural products CC=CC(=O)OCC1=CC(O)C(O)C(O)C1=O PSJQCAMBOYBQEU-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 229920002752 Konjac Polymers 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- 102000014017 Lactoylglutathione lyase Human genes 0.000 description 1
- 108010050765 Lactoylglutathione lyase Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001437 anti-cataract Effects 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 150000001669 calcium Chemical class 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960005188 collagen Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- UFVBOGYDCJNLPM-UHFFFAOYSA-L disodium;9-carboxy-4,5-dioxo-1h-pyrrolo[2,3-f]quinoline-2,7-dicarboxylate Chemical compound [Na+].[Na+].C12=C(C([O-])=O)C=C(C([O-])=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 UFVBOGYDCJNLPM-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 239000012776 electronic material Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000010350 erythorbic acid Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 235000021107 fermented food Nutrition 0.000 description 1
- 239000002657 fibrous material Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 229940046240 glucomannan Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 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
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)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
- 239000000252 konjac Substances 0.000 description 1
- 235000010485 konjac Nutrition 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 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
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- ADXCEOBGDCQCKM-UHFFFAOYSA-N quinoline-2,3-dione Chemical class C1=CC=CC2=NC(=O)C(=O)C=C21 ADXCEOBGDCQCKM-UHFFFAOYSA-N 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 235000010352 sodium erythorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000011755 sodium-L-ascorbate Substances 0.000 description 1
- 235000019187 sodium-L-ascorbate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- DINKXUCRJBUQAZ-UHFFFAOYSA-N tert-butyl 5-bromopyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=CC(Br)=C1 DINKXUCRJBUQAZ-UHFFFAOYSA-N 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
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000019583 umami taste Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/70—Fixation, conservation, or encapsulation of flavouring agents
- A23L27/79—Fixation, conservation, or encapsulation of flavouring agents in the form of films
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
- A23L29/288—Synthetic resins, e.g. polyvinylpyrrolidone
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/042—Gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
Definitions
- the present invention relates to a gel containing reduced pyrroloquinoline quinone and its production.
- Oxidized pyrroloquinoline quinone is generally called PQQ and has been proposed as a new vitamin, and has attracted attention as a useful substance for health supplements, cosmetics, and the like.
- PQQ many physiology such as cell growth promoting action, anti-cataract action action, liver disease demand treatment action, damage healing action, anti-allergic action, reverse transcriptase inhibition action and glyoxalase I inhibition-anticancer action by recent years. Activity has been revealed.
- Non-patent Document 4 It has been reported that reduced PQQ has higher performance than oxidized PQQ with respect to the elimination of active oxygen (Non-patent Document 4), and its provision is required. It has been reported that reduced PQQ makes oxidized PQQ with a reducing agent (Non-patent Document 5), and a document describing that reduced PQQ can be generated from the redox potential of ascorbic acid (Patent Document 1). Is not actually isolated.
- Non-patent Document 1 a crystal structure of PQQ disodium has been reported.
- gel substances are used not only in the food field, medicine, cosmetics, and chromatography, but also in familiar sports shoes and deodorants. Especially for people who have difficulty swallowing (swallowing food) due to aging or illness, and having difficulty in drinking hard tablets, gel-like substances are used because they are easy to drink, unlike touch and handling. It is desired.
- Non-Patent Document 6 Non-Patent Document 6
- the gel has a fibrous form and fits its purpose.
- gelling agents used in the food and pharmaceutical fields are high molecular weight substances such as collagen, hyaluronic acid, agar, and carrageenan.
- a gelling agent in addition to a polymer compound, a low molecular weight compound has also been reported (Non-patent Documents 2 and 3), but no substance that can be used for food is known for the low molecular weight gelling agent.
- the polymer gelling agent is dissolved by heating and then formed by cooling. However, in order to avoid alteration, it is required to use a gelling agent near room temperature for use in the food field.
- a gel in which a reduced pyrroloquinoline quinone salt forms a fibrous structure can be obtained by mixing an aqueous solution of an oxidized pyrroloquinoline quinone salt and a reducing agent at room temperature.
- the salt of reduced pyrroloquinoline quinone can form a gel without being dissolved in a dispersion medium (solvent) under predetermined conditions.
- the present invention is based on this finding.
- An object of the present invention is to provide a reduced pyrroloquinoline quinone gel and a simple and efficient production method thereof.
- Formula (1) (Wherein R 1 , R 2 , and R 3 are the same or different and each represents a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group, or alkynyl group having 1 to 6 carbon atoms)
- a gel comprising a reduced pyrroloquinoline quinone derivative or a salt thereof and a dispersion medium.
- the gel according to any one of (1) to (8), further comprising a polymer gelling agent (10) A dried product obtained by drying the gel according to any one of (1) to (9). (11) A film produced from the gel according to any one of (1) to (9). (12) A food comprising the gel according to any one of (1) to (9) or the dried product according to (10). (13) A pharmaceutical comprising the gel according to any one of (1) to (9) or the dried product according to (10). (14) A cosmetic comprising the gel according to any one of (1) to (9) or the dried product according to (10).
- Formula (2) (Wherein R 1 , R 2 , and R 3 are the same or different and each represents a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group, or alkynyl group having 1 to 6 carbon atoms) ), Which comprises mixing an oxidized pyrroloquinoline quinone derivative or a salt thereof, a dispersion medium, and a reducing agent at 50 ° C. or lower.
- R 1 , R 2 , and R 3 are the same or different and each represents a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group, or alkynyl group having 1 to 6 carbon atoms
- a gel containing a reduced PQQ derivative or a salt thereof and a dispersion medium such as water can be provided.
- a reduced molecular weight gel having a reduced concentration of the reduced PQQ derivative or a salt thereof can be prepared, and the gel can be eaten.
- the gel of the present invention can be uniformly coated and can be provided as a material such as a film.
- the present invention can be made without using a normal gelling agent. Moreover, it can be easily gelled without requiring treatment under high temperature conditions as in the prior art.
- FIG. 1 shows a photograph of the gel of Example 5.
- FIG. 2 shows an optical micrograph of the gel of Example 5.
- FIG. 3 shows the UV spectrum of Sample 6 of Example 6.
- FIG. 4 shows the UV spectrum of Sample 2 of Example 6.
- FIG. 5 shows the UV spectrum of Sample 6 of Example 6.
- FIG. 6 shows the UV spectrum of Example 6, Sample 4.
- FIG. 7 shows the X-ray diffraction results of the dried gel.
- FIG. 8 shows an optical micrograph of the gel in agar.
- FIG. 9 shows an optical micrograph of the gel of Example 1.
- a gel comprising a reduced pyrroloquinoline quinone derivative or a salt thereof is produced by mixing an oxidized pyrroloquinoline quinone derivative or a salt thereof, a dispersion medium, and a reducing agent at 50 ° C. or less. can do.
- a gel comprising a reduced pyrroloquinoline quinone derivative or a salt thereof is a gel substantially comprising a reduced pyrroloquinoline quinone derivative or a salt thereof and a dispersion medium.
- the reduced pyrroloquinoline quinone derivative or a salt thereof associates with each other to form a fibrous structure, and a dispersion medium is contained in the fibrous structure.
- fibrous structure means a three-dimensional network structure formed by physical crosslinking of an aggregate formed by self-association of a pyrroloquinoline quinone derivative or a salt thereof by an interaction other than a covalent bond.
- the gel of the present invention can be said to be a physical gel.
- Non-covalent bonds include non-covalent bonds such as hydrogen bonds, ionic bonds, coordination bonds, ⁇ - ⁇ interactions (stacking), and hydrophobic interactions. It is.
- the gel of the present invention substantially comprises a reduced PQQ derivative having a structure represented by the following formula (1) or a salt thereof and a dispersion medium.
- a reduced PQQ derivative or a salt thereof is a gel having a fibrous structure formed by physical crosslinking.
- R 1 , R 2 , and R 3 are the same or different and represent a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group, or alkynyl group having 1 to 6 carbon atoms, To express).
- the gel of the present invention may contain an oxidized PQQ derivative having a structure represented by the formula (2) or a salt thereof.
- R 1 , R 2 , and R 3 are the same or different and represent a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group, or alkynyl group having 1 to 6 carbon atoms, To express).
- alkyl group means a linear or branched alkyl group.
- alkyl group having 1 to 6 carbon atoms include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, neopentyl, i -Pentyl, t-pentyl, n-hexyl, i-hexyl and the like.
- aralkyl group means an alkyl group in which one of the hydrogen atoms of the alkyl group is substituted with an aryl group.
- An aralkyl group having 7 to 12 carbon atoms is preferable.
- Examples of the “aralkyl group” include benzyl group, phenethyl group, phenylpropyl group, phenylbutyl group and the like.
- alkylaryl group means an aryl group in which one of the hydrogen atoms of the aryl group is substituted with an alkyl group. Preferably, it is an alkylaryl group having 7 to 12 carbon atoms.
- alkylaryl group examples include benzyl group, phenethyl group, phenylpropyl group, phenylbutyl group and the like.
- alkenyl group means a linear or branched alkenyl group.
- An alkenyl group having 2 to 6 carbon atoms is preferable.
- Examples of “alkenyl group” include vinyl group, allyl group, 1-propenyl group, isopropenyl group, 1-buten-1-yl group, 1-buten-2-yl group, 1-buten-3-yl group 2-buten-1-yl group, 2-buten-2-yl group and the like.
- alkynyl group means a linear or branched alkynyl group.
- An alkynyl group having 2 to 6 carbon atoms is preferable.
- Examples of the “alkynyl group” include ethynyl group, 1-propynyl group, 2-propynyl group, butynyl group, pentynyl group, hexynyl group and the like.
- R 1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, more preferably a hydrogen atom or a methyl group, and still more preferably a hydrogen atom.
- R 2 is preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, more preferably a hydrogen atom or a methyl group, and still more preferably a hydrogen atom.
- R 3 is preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, more preferably a hydrogen atom or a methyl group, and still more preferably a hydrogen atom.
- the reduced pyrroloquinoline quinone derivative represented by the formula (1) is preferably a compound in which R 1 , R 2 , and R 3 are all hydrogen atoms or alkyl groups having 1 to 6 carbon atoms, and more preferably Is a compound in which R 1 , R 2 , and R 3 are all hydrogen atoms or methyl groups, and more preferably a compound in which R 1 , R 2 , and R 3 are all hydrogen atoms (so-called reduction) Type pyrroloquinoline quinone).
- the oxidized pyrroloquinoline quinone derivative represented by the formula (2) is preferably a compound in which R 1 , R 2 , and R 3 are all hydrogen atoms or alkyl groups having 1 to 6 carbon atoms, and more preferably Is a compound in which R 1 , R 2 , and R 3 are all hydrogen atoms or methyl groups, and more preferably a compound in which R 1 , R 2 , and R 3 are all hydrogen atoms (so-called pyrrolo Quinolinequinone).
- the reduced PQQ derivative of the formula (1) or the oxidized PQQ derivative of the formula (2) used in the present invention (hereinafter referred to as “reduced pyrroloquinoline quinone derivative of the formula (1)” and “oxidized pyrrolo of the formula (2)””
- Examples of the salt of “pyrroloquinoline quinone derivative” or “PQQ derivative” when not distinguished from “quinoline quinone derivative” include alkali metal salts, alkaline earth metal salts, ammonium salts and the like. In particular, alkali metal salts are preferable in that they are water-soluble.
- alkali metal salt examples include sodium, potassium, lithium, calcium, magnesium, cesium, rubidium and the like. Preferably, it is a sodium salt.
- the alkali metal salt of the PQQ derivative may be substituted with 1 to 3 alkali metals, and may be any of a monoalkali metal salt, a dialkali metal salt, and a trialkali metal salt, but is preferably a dialkali metal salt.
- the alkali metal salt of the PQQ derivative is particularly preferably a disodium salt.
- oxidized PQQ derivative of the formula (2) or a salt thereof a commercially available product can be obtained, and it can also be produced by a known method.
- the oxidized pyrroloquinoline quinone derivative or a salt thereof is preferably a salt of an oxidized pyrroloquinoline quinone derivative.
- the reduced pyrroloquinoline quinone derivative or a salt thereof is preferably a salt of a reduced pyrroloquinoline quinone derivative.
- the reduced PQQ derivative or a salt thereof is preferably contained in a mole percentage of 0.1% to 100% of the total PQQ (reduced PQQ and oxidized PQQ) derivative or a salt thereof contained in the gel. More preferably, the content of the reduced PQQ derivative or a salt thereof is 50 mol% or more, further preferably the content of the reduced PQQ derivative or a salt thereof is 60 mol% or more, and even more preferably, the content of the reduced PQQ derivative or a salt thereof. The content is 70 mol% or more, particularly preferably the content of the reduced PQQ derivative or a salt thereof is 80 mol% or more, and most preferably the content of the reduced PQQ derivative or a salt thereof is 90 mol% or more.
- the reduced PQQ derivative or a salt thereof is less soluble than the oxidized PQQ derivative or a salt thereof, and easily forms a gel structure.
- the gel of the present invention preferably contains the reduced PQQ derivative or a salt thereof in an amount of 0.001 to 70% by weight in the total gel weight. More preferably from 0.05 to 5% by weight, still more preferably from 0.05% by weight to less than 0.7% by weight, even more preferably from 0.05 to 0.4% by weight, especially Preferably, it is 0.05 to 0.3% by weight.
- it is thinner than this concentration, it dissolves and does not gel in the case of a solvent such as pure water.
- concentration is higher than this range, it becomes clayy and it cannot be determined whether or not a gel state is formed.
- the reduced PQQ derivative or salt thereof, or the oxidized PQQ derivative or salt thereof is in a solid state and may be either amorphous or crystalline. It is thought that crystallization proceeds from amorphous. Crystallization can be examined by X-ray diffraction. For example, when the apparatus is RINT 2500 manufactured by Rigaku Corporation, X-ray: Cu / tube voltage 40 kV / tube current 100 mA, scan speed: 4.000 ° / min, sampling width: 0.020 °, the gel of the present invention is used.
- the contained reduced PQQ derivative or a salt thereof is a crystallized substance of 8.14, 10.41, 19.74, 29.94 ⁇ 0.08 °.
- It has a fibrous structure formed by combining reduced pyrroloquinoline quinone derivatives or salts thereof with each other by mixing oxidized pyrroloquinoline quinone derivatives or salts thereof, a dispersion medium, and a reducing agent at 50 ° C. or lower.
- a gel can be produced.
- Mixing of the oxidized pyrroloquinoline quinone derivative or salt thereof, the dispersion medium, and the reducing agent may be performed by mixing each component at a time or separately. You may mix previously.
- an oxidized pyrroloquinoline quinone derivative or a salt thereof and a dispersion medium can be mixed, and the obtained mixed solution (solution) and a reducing agent can be mixed.
- the reducing agent may also be mixed with the dispersion medium.
- the dispersion medium examples include water, organic solvents, oils and fats.
- the organic solvent include ethanol, propanol, butanol, glycerin, propylene glycol, ethyl lactate, methyl ⁇ -hydroxyisobutyrate, and fats and oils such as rice oil, coconut oil, corn oil, olive oil, rapeseed oil, triacetin, soybean oil, And medium chain fatty acid glycerin esters.
- it is water.
- the dispersion medium is water, it can be a hydrous gel (hydrogel). It is also possible to exchange the dispersion medium by exchanging the dispersion medium.
- the reducing agent that can be used is not particularly limited, and typical reducing agents such as sodium borohydride, Na 2 S 2 O 4 , phenylhydrazine, hydrogen, phenylthiol, NADPH, NADH, ascorbic acid, glutathione, cysteine, etc. can be used. . Preferred are hydrogen, NADPH, NADH, ascorbic acid, glutathione, and cysteine, which are highly safe. More preferred is ascorbic acid.
- ascorbic acid examples include rhamno-ascorbic acid, arabo-ascorbic acid, gluco-ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xylo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid, allo-ascorbic acid Acids, erythro-ascorbic acid, 6-desoxyascorbic acid and the like ascorbic acid (ascorbic acid analogs) may be used, and their esters and salts (eg, palmitate, stearate, sodium salt, calcium) Salt, etc.).
- esters and salts eg, palmitate, stearate, sodium salt, calcium
- L form eg. L-ascorbic acid, sodium L-ascorbate, etc.
- D form eg. D-arabo-ascorbic acid, D-arabo-sodium ascorbate, etc.
- racemate There may be.
- the reducing agent used in the present invention can be used as a reducing agent, or can be used as a solution of a reducing agent.
- the reducing agent can be used by dissolving in the dispersion medium, but it is preferably used as an aqueous solution of the reducing agent.
- the reducing agent solution can be prepared to be, for example, 0.1 to 500 g / l, and preferably 0.5 to 150 g / l.
- the amount of the reducing agent to be used may be 0.1 to 5000 times the number of moles of the oxidized PQQ derivative or its salt.
- the reaction is likely to proceed when added in excess, so 1.1 to 1000 times is preferable. More preferably, it is 1.1 times to 100 times. That is, in the production method according to the present invention, the molar ratio of the oxidized PQQ derivative or a salt thereof and the reducing agent is 1: 0.1 to 5000, preferably 1: 1.1 to 1000, more preferably 1: 1.1 to 100.
- the reducing agent may remain inside the gel, and the excess reducing agent can enhance the maintenance of the reduced PQQ derivative or a salt thereof, and can be a stable product.
- the method for producing the gel of the present invention is easy to change depending on conditions such as salt concentration, precursor, temperature, etc., but can be generalized as follows. Gelation is enabled by adding oxidized PQQ or a salt thereof to a dispersion medium and adding a reducing agent at 50 ° C. or lower and pH 0 to 14 for reaction.
- Oxidized PQQ may be completely dissolved in the dispersion medium or may remain undissolved as a suspension.
- the oxidized PQQ derivative or a salt thereof is 0.001 to 70% by weight in the dispersion medium. It is preferably 0.005 to 10% by weight, more preferably 0.05% by weight or more and less than 0.7% by weight. If the concentration is high, the gel becomes hard and stable, but the amount of oxidized PQQ or reduced PQQ used increases and is not economical. Moreover, the part which is not used for gel structure formation increases, and it is not efficient. On the other hand, it is fragile at a concentration lower than the above range.
- the concentration of the oxidized pyrroloquinoline quinone derivative or its salt can be less than the solubility.
- “solubility” means the limit of solute dissolution in a solvent, and can be represented by the concentration of the solute in the saturated solution.
- the solubility of the oxidized pyrroloquinoline quinone derivative or a salt thereof can be appropriately determined depending on the temperature of the mixture. For example, the solubility of oxidized pyrroloquinoline quinone disodium is 0.299 g per 100 g of water at 25 ° C.
- the weight concentration of the oxidized PQQ derivative or a salt thereof is 0.001 to 70 wt%, preferably 0.005 to 10 wt%, more preferably 0.05 wt% or more and less than 0.7 wt% in the dispersion medium. More preferably, it can be adjusted to 0.05 to 0.4% by weight, and still more preferably 0.05 to 0.3% by weight.
- the oxidized PQQ derivative or a salt thereof is reduced to a reduced PQQ derivative or a salt thereof, and a fibrous solid grows slowly and gelation occurs.
- the solubility of oxidized PQQ is too low and the reduction reaction does not occur. If it is too high, it will not grow into a fibrous solid.
- it is ⁇ 10 ° C. to 50 ° C.
- the temperature of the obtained mixture can be ⁇ 10 ° C. to 50 ° C., but from the viewpoint of operability, it is more preferably 0 to 45 ° C., further preferably 0 to 30 ° C.
- the obtained mixture is preferably reacted for 1 minute or longer, and more preferably 10 minutes, since it can be surely gelled. Preferably, it is 1 minute to 72 hours, more preferably 10 minutes to 48 hours.
- oxidized PQQ salt is also gelled (WO2012 / 020767).
- an oxidized PQQ gel When an oxidized PQQ gel is prepared, it must be prepared at a high concentration to dissolve and gel. Therefore, it is difficult to form a uniform solution.
- a gel When a gel is formed only from oxidized PQQ, it is necessary to have a concentration that does not dissolve. In order to make a gel stably, it is preferably 0.7% by weight or more. A gel cannot be formed at 0.3% by weight at room temperature.
- the dispersion medium examples include water, organic solvents, oils and fats.
- the organic solvent include ethanol, propanol, butanol, glycerin, propylene glycol, ethyl lactate, methyl ⁇ -hydroxyisobutyrate, and fats and oils such as rice oil, coconut oil, corn oil, olive oil, rapeseed oil, triacetin, soybean oil, And medium chain fatty acid glycerin esters.
- it is water.
- the dispersion medium is water, it can be a hydrous gel (hydrogel). The gelled product can be exchanged by exchanging the contained dispersion medium.
- the pH may be in the range of 0-14, but is preferably 1-9, more preferably 1-6. It is preferable to increase the concentration of the reduced PQQ derivative or a salt thereof because it is easily dissolved in the alkali.
- the reduction with ascorbic acid is preferably under acidic conditions.
- mixing of the oxidized pyrroloquinoline quinone derivative or a salt thereof, the dispersion medium, and the reducing agent can be performed at pH 0 to 14, preferably 1 to 9, and more preferably 1 to 6. Yes, more preferably 3-6.
- the state where the reduced PQQ derivative or its salt and the oxidized PQQ derivative or its salt are mixed in the gel can be prepared by adjusting the ratio of the amount of the oxidized PQQ derivative or its salt and the reducing agent.
- the presence of the reduced PQQ derivative or its salt strengthens the bond between molecules and promotes gelation.
- the reduced PQQ derivative or its salt is oxidized to the oxidized PQQ derivative or its salt by oxygen, the gel shape is changed. There is no particular problem if it is maintained.
- the present invention is characterized in that PQQ itself can be gelled from a salt of PQQ and a dispersion medium (water), and is produced without using a normal gelling agent. be able to.
- the reduced PQQ derivative or a salt thereof has a low molecular weight and needs to be fiberized as a high polymer for gelation. In the present invention, it is considered that the compound does not dissolve due to the formation of a reduced PQQ derivative or a salt thereof, and is polymerized by noncovalent bonding to become fibrillated.
- the gel of the present invention can thus be easily produced without forming a fiber at a high temperature as in the prior art.
- the intermolecular molecules of the reduced PQQ derivative or its salt are formed by ionic bonds or hydrogen bonds with alkali metals.
- concentration of the PQQ derivative or a salt thereof is high, the original crystal structure is mixed in addition to the fiber structure that gels, but there is no particular problem if gelation occurs. Moreover, there is no problem even if PQQ powder is mixed with the substance once gelled.
- Non-Patent Document 1 indicates that there are intermolecular hydrogen bonds and ionic bonds in the disodium salt of PQQ, and there is also stacking of aromatic rings.
- the fiberized reduced PQQ has a different structure from the crystal, it can be used as a reference.
- the hydroxyl group of hydroquinone is also involved as a hydrogen bond, thereby strengthening the bonding force between molecules.
- the content of the reduced PQQ derivative or salt thereof in the generated gel is determined by the amount of the oxidized PQQ derivative or salt thereof to be charged, but the concentration can be changed by diluting or concentrating this.
- a dispersion medium may be added. Concentration can be performed by removing excess dispersion medium by centrifugation or filtration, or evaporating the dispersion medium. If the fibrous structure can be maintained, a gel containing a solvent is obtained.
- the gel of the present invention can also exchange the dispersion medium.
- a method for exchanging the dispersion medium a method of washing the gel with an exchange dispersion medium on a filter or adding an exchange dispersion medium and repeating the operation of removing the supernatant is simple.
- the dispersion medium to be exchanged there is no problem even if the liquid is replaced with ethanol, propanol, butanol, oils or the like as a liquid.
- not only a water-containing gel but also a gel containing an organic solvent can be used.
- polymer gelling agent examples include gelatin, agar, carrageenan, collagen, fucoidan, hyaluronic acid, konjac, glucomannan, pectin, locust bean gum, xanthan gum, gellan gum, starch, egg white and the like. These may be mixed in a gelled state, or may be gelled simultaneously with mixing.
- the gel of the present invention can be used for foods, cosmetics, pharmaceuticals, agricultural chemicals, agricultural supplies, electronic materials, filter materials, and the like.
- additives When used in foods and cosmetics, other components necessary for it can be added as necessary.
- additives include flavorings, acidulants, salts, sweeteners, umami ingredients, fruit juice, fermented foods, lipids, moisturizers, whitening agents, herbal extracts, tea, coffee, emulsifiers, glycerin, preservatives, antibacterial agents, Examples include steroids, methyl salicylate, vitamins, indomethacin, etc., and these may be added as necessary.
- sweetener monosaccharide, disaccharide, oligosaccharide, and artificial sweetener sugar can be mixed. More specifically, fructose, glucose, galactose, sorbitol, xylitol, erythritol, trehalose, palatinit, aspartame, acesulfame K, sucralose, licorice extract, lacanca syrup, honey and the like can be mentioned.
- a fibrous structure comprising a reduced PQQ derivative or a salt thereof
- drying method include freeze-drying, spray dry drying, and heat drying after solvent replacement.
- the solid obtained by drying this gel has a feature that it has a large surface area and is fibrous, which makes it different from ordinary powders in texture and appearance, and is particularly effective in the fields of food, cosmetics and medicine. It can also be cast on a plate to form a film.
- the fiber thickness of the fibrous structure of the present invention is 0.02 to 2000 ⁇ m, preferably 0.05 to 500 ⁇ m, more preferably 0.05 to 50 ⁇ m, and still more preferably 0.05 to 5 ⁇ m. can do.
- the thickness of the fiber can be measured using a microscope (an electron microscope, an optical microscope, a probe, etc.).
- the fibrous structure (fibrous substance) of the present invention can be entangled with powder from the fiber structure.
- a tablet when a tablet is formed, it can be formed by mixing with powder of oxidized PQQ or reduced PQQ.
- powder of oxidized PQQ or reduced PQQ As a result, it is possible to reduce the use of a binder or the like that was necessary for tableting from oxidized PQQ or reduced PQQ powder. It is preferable that 1% or more of the reduced PQQ is contained in the final molded product in the number of moles combined with the oxidized PQQ.
- a gel comprising a sodium salt of reduced pyrroloquinoline quinone produced by mixing a solution of a sodium salt of oxidized pyrroloquinoline quinone and a reducing agent at 50 ° C. or lower, and It is the manufacturing method.
- the weight concentration of the oxidized pyrroloquinoline quinone sodium salt in the mixture (solution) is preferably 0.05 wt% or more and less than 0.7 wt%, more preferably 0.05 to 0.4 wt%. %, Even more preferably 0.05 to 0.3% by weight.
- the present invention comprises a sodium salt of reduced pyrroloquinoline quinone produced by mixing a solution of oxidized pyrroloquinoline quinone sodium salt and an ascorbic acid solution at 50 ° C. or lower. It is a gel and its manufacturing method.
- the weight concentration of the oxidized pyrroloquinoline quinone sodium salt in the mixture (solution) is preferably 0.05 wt% or more and less than 0.7 wt%, more preferably 0.05 to 0.4 wt%. %, Even more preferably 0.05 to 0.3% by weight.
- R 1 , R 2 and R 3 are the same or different and each represents a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group or alkynyl group having 1 to 6 carbon atoms.
- R 1 , R 2 and R 3 are the same or different and each represents a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group or alkynyl group having 1 to 6 carbon atoms
- a food comprising the gel according to any one of (3) to (8) or the dried product according to (9).
- a medicament comprising the gel according to any one of (3) to (8) or the dried product according to (9).
- a cosmetic comprising the gel according to any one of (3) to (8) or the dried product according to (9).
- an oxidized pyrroloquinoline quinone or a salt thereof represented by the formula (2) (Wherein R 1 , R 2 and R 3 are the same or different and each represents a hydrogen atom, a phenyl group, or an alkyl group, aralkyl group, alkylaryl group, alkenyl group or alkynyl group having 1 to 6 carbon atoms)
- a method for producing a gel comprising mixing a reducing agent in a dispersion medium at 50 ° C. or lower.
- XRD powder X-ray diffraction
- the optical micrographs were taken with a NIKON microscope TE-2000S and a 40 ⁇ objective lens.
- UV measurement was performed using a HITACHI U-2000 Spectrophotometer.
- Example 1 Preparation of gel (1) 3 g of oxidized PQQ disodium powder was dissolved in 1 L of water to prepare a 3 g / L PQQ disodium solution. 10 g of ascorbic acid was dissolved in 90 ml of water to prepare a 10% ascorbic acid solution. 4 ml of 3 g / L oxidized PQQ disodium solution and 0.1 ml of 10% ascorbic acid solution were placed in a polystyrene test tube and allowed to stand overnight at room temperature to obtain a black gelled product. The pH at the time of mixing was 3.7. Moreover, this gel was washed with methyl ⁇ -hydroxyisobutyrate, and the result of observation with an optical microscope is shown in FIG. Crystals were not found and were fibrous.
- Example 2 Preparation of gel (2) 4 ml of 3 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 1 and 0.2 ml of 10% ascorbic acid solution were placed in a polystyrene test tube and cooled on ice for 30 minutes. Then, it was left overnight at room temperature. As a result, a red gelled product was obtained. The pH at this time (during mixing) was 3.7.
- Example 3 Preparation of gel (3) 4 ml of 3 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 1 and 0.1 ml of 10% ascorbic acid solution were placed in a polystyrene test tube and cooled on ice for 30 minutes. Thereafter, the refrigerator was left at about 10 ° C. overnight. As a result, a red gelled product was obtained. The pH at this time (during mixing) was 3.7.
- Example 4 Preparation of gel (4) 4 ml of 3 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 1 and 1 ml of 10% ascorbic acid solution were placed in a polystyrene test tube and cooled on ice for 30 minutes. Thereafter, the refrigerator was left at about 10 ° C. overnight. As a result, a brown gelled product was obtained. At this time (during mixing), the pH was 3.1.
- Example 5 Preparation of gel (5) 5 g of oxidized PQQ disodium powder was added to 1 L of water and dissolved at 75 ° C. This was brought to room temperature to make a supersaturated 5 g / L PQQ disodium solution. 4 ml of 5 g / L PQQ disodium solution and 1 ml of 10% ascorbic acid solution were placed in a polypropylene container and cooled at about 10 ° C. in a refrigerator for 1 hour. After that, when left at 30 ° C. for 2 hours, a dark red gel was formed and the whole solidified. The pH at this time (during mixing) was 3.3. A photograph of this gel made with a 15 ml centrifuge tube is shown in FIG.
- Example 6 Absorbance measurement by UV spectrum Each sample was prepared as follows, and the absorbance was measured using a quartz cell having an optical path length of 1 mm.
- Sample 1 Gel 0.20 ml of a 5 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 5 and 0.05 ml of a 10% ascorbic acid solution were placed in a polypropylene container and cooled in a refrigerator at about 10 ° C. for 1 hour. After that, when left at 30 ° C. for 2 hours, a dark red gel was formed and the whole solidified. To this was added 4.75 ml of water. This solution was further diluted 1/4 with water. The absorbance measurement results are shown in FIG.
- Sample 2 Ascorbic acid mixed (PQQ disodium 0.05 g / L used) 0.20 ml of 5 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 5 and 0.05 ml of 10% ascorbic acid solution were placed in a polypropylene container, and 4.75 ml of water was immediately added. This solution was further diluted 1/4 with water. The absorbance measurement results are shown in FIG.
- Sample 3 Reduced PQQ (using PQQ disodium 0.05 g / L)
- a 0.2 g of 5 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 5 and 0.05 ml of a 10% ascorbic acid solution were placed in a polypropylene container and left at 70 ° C. for 3 hours, a black solid was obtained. Precipitated. To this solid was added 1 ml of dimethyl sulfoxide and dissolved, and 3.75 ml of water was added. This solution was further diluted 1/4 with water. The absorbance measurement results at this time are shown in FIG.
- Example 7 Gel concentration operation and dispersion medium exchange
- the gel prepared in Example 5 was centrifuged and treated at 2000 rpm for 30 minutes. The volume of the gel was 1/4, and a concentrate was formed by discarding the supernatant.
- As the dispersion medium 2N hydrochloric acid, ethanol, isopropanol, and methyl ⁇ -hydroxyisobutyrate were used, respectively.
- the dispersion medium was added in the same volume as the concentrated gel, centrifuged, and the supernatant was discarded. This was repeated twice to obtain a dispersion medium exchange gel.
- the dispersion medium could be exchanged and the gel substance did not dissolve and collapse. Different gels of four types of dispersion media could be made.
- Example 8 Powder X-ray diffraction The gel obtained in Example 5 was washed with methyl ⁇ -hydroxyisobutyrate and dried under reduced pressure. When this was measured by powder X-ray, no peak was found and the film was amorphous. The gel obtained by the same operation as in Example 5 was filtered at room temperature for 2 hours and then dried under reduced pressure. When this was measured by powder X-ray, it was obtained as a crystallized substance of 8.14, 10.41, 19.74, 29.94 ⁇ 0.08 °. The powder X-ray measurement results are shown in FIG.
- Comparative Example 1 4 ml of 5 g / LPQQ oxidized disodium solution prepared in the same manner as in Example 5 and 1 ml of 10% ascorbic acid solution were placed in a polystyrene test tube and cooled at about 10 ° C. in a refrigerator for 1 hour. Thereafter, a black solid precipitated when left at 70 ° C. for 2 hours. Reduced PQQ powder was obtained. As a result of powder X-ray analysis of this solid, it was amorphous.
- Comparative Example 2 4 ml of 5 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 5 was cooled with ice and allowed to stand at 30 ° C. for 2 hours. Although crystals were precipitated, gelation did not occur.
- Example 9 Mixing of gel and oxidized PQQ 1 mL of the gel prepared in Example 5 and 0.3 g of PQQ disodium powder were mixed. A homogeneous mixture was obtained. The reductant content of this mixture was 1.6%. This was dried under reduced pressure to obtain a solid red solid.
- Example 10 Preparation of fibrous substance in agar (agarose) To 40 ml of 3 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 1, 0.40 g of agarose manufactured by Wako Pure Chemical Industries, Ltd. was added. This was heated in a microwave oven to completely dissolve the agarose. 4 ml of this solution was placed in a petri dish and cooled to room temperature to solidify. To this, 1 ml of 10% ascorbic acid solution was added and left on ice for 1 hour. Further, a fibrous substance was formed by microscopic observation after 1 hour at 30 ° C. The micrograph is shown in FIG. Furthermore, the fibrous substance remained even if it was left overnight. Fibrous material was produced even in agar.
- Example 11 Gelation in the Presence of Sugar Into 4 ml of 5 g / L of oxidized PQQ disodium solution prepared in the same manner as in Example 5, 0.3, 0.6, 0.9, 1.2, 1. 5 g sorbitol was added and dissolved. This was mixed with 1 ml of a 10% ascorbic acid solution and cooled in a refrigerator at about 10 ° C. for 1 hour. Thereafter, when the mixture was left at 30 ° C. for 2 hours, all the mixed liquids became dark red gels, and the whole solidified. However, what mixed sorbitol 1.2 and 1.5g was a soft gel. Addition of sugar makes gel formation difficult, but gelation was possible even at a concentration of 20% by weight or more, and there was no practical problem.
- Example 12 Film production from gel 1 ml of the gel of Example 5 was mixed with 10 ml of methanol and centrifuged. The supernatant was discarded, 1 ml of methanol was added, put into a petri dish, and dried under reduced pressure to obtain a film on the petri dish.
- Example 13 Preparation of film from gel 1 ml of the gel of Example 5 was mixed with 10 ml of 2-propanol and centrifuged. The supernatant was discarded, 1 ml of 2-propanol was added, placed in a petri dish, and dried under reduced pressure to obtain a film on the petri dish.
- Example 14 Film production from gel 4 ml of the gel of Example 5 was placed on filter paper No5 and suction filtered. After washing with 20 ml of 2-propanol and drying under reduced pressure with filter paper, the filter paper was uniformly coated.
- Comparative Example 3 The mixed solution reacted at 75 ° C. in Comparative Example 1 was centrifuged and the supernatant was discarded. After washing with 10 ml of 2-propanol, 1 ml of 2-propanol was added, placed in a petri dish, and dried under reduced pressure. It was dispersed on top and did not become a film.
- Comparative Example 4 A 5 g / L oxidized PQQ disodium solution prepared in the same manner as in Example 5, 4 ml, and 1 ml of a 10% ascorbic acid solution were mixed and immediately dried under reduced pressure. Since drying started immediately after mixing, water evaporated before gelation occurred. Therefore, the powder was sparse and not a film.
- Examples 15 to 17 and Comparative Examples 5 to 6 The same raw material as in Example 1 was used, and the experiment was performed by changing the amount and temperature of the 10% ascorbic acid solution. The results are shown below.
- the gel of the present invention is effective in the fields of foods, functional foods, pharmaceuticals, quasi drugs, functional materials or cosmetics.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Birds (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Dispersion Chemistry (AREA)
- Mycology (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
Description
(1)式(1):
(2)還元型ピロロキノリンキノン誘導体またはその塩が、互いに会合して繊維状構造を形成していることを特徴とする、(1)に記載のゲル。
(3)還元型ピロロキノリンキノン誘導体またはその塩が、全ゲル重量に対して0.001~70重量%である、(1)または(2)に記載のゲル。
(4)還元型ピロロキノリンキノン誘導体またはその塩が、全ゲル重量に対して0.05重量%以上0.7重量%未満である、(1)または(2)に記載のゲル。
(5)還元剤をさらに含んでなる、(1)~(4)のいずれかに記載のゲル。
(6)分散媒が、水である、(1)~(5)のいずれかに記載のゲル。
(7)式(2):
(8)還元型ピロロキノリンキノン誘導体またはその塩が、全ピロロキノリンキノン誘導体またはその塩のモル数中に0.1モル%以上含まれる、(7)に記載のゲル。
(9)高分子ゲル化剤をさらに含んでなる、(1)~(8)のいずれかに記載のゲル。
(10)(1)~(9)のいずれかに記載のゲルを乾燥した乾燥体。
(11)(1)~(9)のいずれかに記載のゲルから製造されたフィルム。
(12)(1)~(9)のいずれかに記載のゲルまたは(10)に記載の乾燥体を含んでなる、食品。
(13)(1)~(9)のいずれかに記載のゲルまたは(10)に記載の乾燥体を含んでなる、医薬。
(14)(1)~(9)のいずれかに記載のゲルまたは(10)に記載の乾燥体を含んでなる、化粧品。
(15)式(2):
(16)分散媒中の酸化型ピロロキノリンキノン誘導体またはその塩の濃度が、0.05重量%以上0.7重量%未満である、(15)に記載の製造方法。
還元剤の溶液は、例えば、0.1~500g/lとなるように調製することができるが、好ましくは、0.5~150g/lである。
(1)式(1)に示す還元型ピロロキノリンキノン又はその塩と分散媒を含むゲル。
(2)還元型ピロロキノリンキノン又はその塩が、互いに物理架橋して繊維状構造を形成していることを特徴とする、(1)に記載のゲル。
(3)還元型ピロロキノリンキノン又はその塩が全ゲル重量に対して0.001~70重量%である、(1)又は(2)に記載のゲル。
(4)還元剤をさらに含むことを特徴とする(3)に記載のゲル。
(5)分散媒が水であることを特徴とする、(3)又は(4)に記載のゲル。
(6)式(2)に示す酸化型ピロロキノリンキノン又はその塩をさらに含む(3)~(5)のいずれかに記載のゲル。
(7)還元型ピロロキノリンキノンが全ピロロキノリンキノンのモル数中に0.1モル%以上含まれる(6)に記載のゲル。
(8)高分子ゲル化剤をさらに含んでなる、(3)~(7)のいずれかに記載のゲル。
(9)(3)~(8)のいずれかに記載のゲルを乾燥した乾燥体。
(10)(1)~(8)のいずれかに記載のゲルから作ったフィルム。
(11)(3)~(8)のいずれかに記載のゲル又は(9)に記載の乾燥体を含んでなる、食品。
(12)(3)~(8)のいずれかに記載のゲル又は(9)に記載の乾燥体を含んでなる、医薬。
(13)(3)~(8)のいずれかに記載のゲル又は(9)に記載の乾燥体を含んでなる、化粧品。
(14)式(2)に示す酸化型ピロロキノリンキノン又はその塩と
還元剤を、分散媒中、50℃以下で混合することを特徴とするゲルの製造方法。
(15)分散媒中のピロロキノリンキノンの濃度が0.05重量%以上0.7重量%未満となる様に混合することを特徴とする(14)記載の製造方法。
装置:株式会社RIGAKU製RINT2500
X線:Cu/管電圧40kV/管電流100mA
スキャンスピード:4.000°/min
サンプリング幅:0.020°
酸化型のPQQジナトリウム粉末3gを水1Lに溶解して3g/L PQQジナトリウム溶液を作製した。アスコルビン酸10gを水90mlに溶かし、10%アスコルビン酸溶液を作製した。
3g/L酸化型PQQジナトリウム溶液4mlと10%アスコルビン酸溶液0.1mlをポリスチレン製試験管に入れ、室温で一晩放置し、黒色のゲル化物を得た。混合時のpHは3.7であった。
また、このゲルをαーヒドロキシイソ酪酸メチルで洗って、光学顕微鏡観察した結果を図9に示す。結晶は見当たらず、繊維状になっていた。
実施例1と同様にして調製した3g/L酸化型PQQジナトリウム溶液4mlと10%アスコルビン酸溶液0.2mlをポリスチレン製試験管に入れ、氷の上で30分冷却した。その後室温で一晩放置した。その結果、赤色のゲル化物を得た。このとき(混合時)のpHは3.7であった。
実施例1と同様にして調製した3g/L酸化型PQQジナトリウム溶液4mlと10%アスコルビン酸溶液0.1mlをポリスチレン製試験管に入れ、氷の上で30分冷却した。その後冷蔵庫約10℃で一晩放置した。その結果、赤色のゲル化物を得た。このとき(混合時)のpHは3.7であった。
実施例1と同様にして調製した3g/L酸化型PQQジナトリウム溶液4mlと10%アスコルビン酸溶液1mlをポリスチレン製試験管に入れ、氷の上で30分冷却した。その後冷蔵庫約10℃で一晩放置した。その結果、茶色のゲル化物を得た。このとき(混合時)のpHは3.1であった。
酸化型PQQジナトリウム粉末5gを水1Lに加え、75℃で溶解した。これを室温にして過飽和な5g/LのPQQジナトリウム溶液を作った。
5g/L PQQジナトリウム溶液4mlと10%アスコルビン酸溶液1mlをポリプロピレン製容器に入れ、冷蔵庫約10℃で1時間冷却した。その後、2時間、30℃に置いておくと暗赤色ゲルになり、全体が固まった。このとき(混合時)のpHは3.3であった。
このゲルを15mlの遠心分離用チューブで作成した写真を図1に示す。逆さまにしても流れ落ちず、完全にゲル化している。
また、このゲルをαーヒドロキシイソ酪酸メチルで洗って、光学顕微鏡観察した結果を図2に示す。ゲルは赤い塊として観察できた。また、一部、繊維状のモノが見えた。ゲルのほとんどは微細な繊維になっているため、光学顕微では全体が均一なフィルムとして見えた。
各サンプルの調製を以下の様に行い、光路長1mmの石英セルを使用して吸光度測定を行った。
実施例5と同様にして調製した5g/L酸化型PQQジナトリウム溶液0.20mlと10%アスコルビン酸溶液0.05mlをポリプロピレン製容器に入れ、冷蔵庫約10℃で1時間冷却した。その後、2時間、30℃に置いておくと暗赤色ゲルになり、全体が固まった。これに水を4.75ml加えた。この溶液をさらに1/4に水で希釈した。吸光度測定結果を図3に示す。
実施例5と同様にして調製した5g/L酸化型PQQジナトリウム溶液0.20mlと10%アスコルビン酸溶液0.05mlをポリプロピレン製容器に入れ、すぐに水を4.75ml加えた。この溶液をさらに1/4に水で希釈した。吸光度測定結果を図4に示す。
実施例5と同様にして調製した5g/L酸化型PQQジナトリウム溶液0.20mlと10%アスコルビン酸溶液0.05mlをポリプロピレン製容器に入れ、3時間、70℃に置いておくと黒い固体が析出した。
この個体にジメチルスルホキシド1ml加えて溶かし、水を3.75ml加えた。この溶液をさらに1/4に水で希釈した。このときの吸光度測定結果を図5に示す。なお、この実験で得た固体は水だけでは完全に溶けないため、ジメチルスルホキシドで溶解したのち水で希釈して測定した。
また、この固体に塩酸を加えてpHを1以下にした。これを遠心分離し、上澄みを捨てた。脱気した塩酸水溶液で洗い、窒素気流によって乾燥した。ここに重ジメチルスルホキシドを加え、窒素気流下でNMR管につめた。
JEOL製500MHz NMR, JNMーECA500 スペクトルメーターを使用し、13C-NMRを室温測定した。その結果、105.7, 111.0, 119.4, 122.9, 123.6, 128.1, 131.3, 134.2, 137.8, 140.9, 142.6, 162.2, 165.5, 170.1 ppm(DMSO-d6: 39.5ppm基準)であった。この値は非特許文献5に記載の還元型PQQと一致しており、還元体の生成を確認した。
実施例5と同様にして調製した5g/L酸化型PQQジナトリウム溶液0.20mlと水0.05mlをポリプロピレン製容器に入れ、すぐに水を4.75ml加えた。吸光度測定結果を図6に示す。
サンプル1(ゲル):100%
サンプル2(混合直後):99.8%
実施例5で作ったゲルを遠心分離器にかけ、2000rpmで30分処理した。ゲルの体積は1/4になっており、上澄みを捨てることで濃縮体を形成した。分散媒としては、それぞれ、2N塩酸、エタノール、イソプロパノール、αーヒドロキシイソ酪酸メチルを使用した。分散媒を濃縮ゲルと同じ体積加え、遠心分離して上澄みを捨てた。これを2回繰り返し、分散媒交換ゲルを得た。分散媒の交換は行うことができ、ゲル物質が溶解して崩壊することはなかった。4種類の分散媒の異なるゲルを作ることができた。
実施例5で得たゲルをαーヒドロキシイソ酪酸メチルで洗浄後、減圧乾燥した。これを粉末X線で測定するとピークは見つからず、アモルファスであった。
実施例5と同様の操作で得たゲルを室温でろ過処理を2時間かけて行ったのち、減圧乾燥した。これを粉末X線で測定すると8.14、10.41,19.74,29.94±0.08°の結晶化した物質として得ることができた。この粉末X線測定結果を図7に示す。
実施例5と同様にして調製した5g/LPQQ酸化型ジナトリウム溶液4mlと10%アスコルビン酸溶液1mlをポリスチレン製試験管に入れ、冷蔵庫約10℃で1時間冷却した。その後、2時間、70℃に置いておくと黒い固体が沈殿した。還元型PQQ粉末を得た。この固体の粉末X線分析の結果、アモルファスであった。
実施例5と同様にして調製した5g/L酸化型PQQジナトリウム溶液4mlを氷で冷却して1時間、30℃で2時間放置した。結晶が析出していたがゲル化は生じていなかった。
実施例5で作製したゲル1mLとPQQジナトリウム粉末0.3gを混合した。均一な混合物を得た。この混合物の還元体含有量は1.6%であった。これを減圧乾燥して固まった赤色固体を得た。
実施例1と同様にして調製した3g/L酸化型PQQジナトリウム溶液40mlに和光純薬製アガロース0.40g加えた。これを電子レンジで加熱してアガロースを完全に溶解した。この溶液4mlをシャーレに入れて室温に冷却して固めた。ここに10%アスコルビン酸溶液1mlを加え、氷の上で1時間放置した。さらに30℃にして1時間後顕微鏡観察すると繊維状物質が形成していた。その顕微鏡写真を図8に示す。さらに一晩放置しても繊維状物質が残留していた。寒天中でも繊維状物質ができた。
実施例5と同様にして調製した5g/Lの酸化型PQQジナトリウム溶液4mlに0.3、0.6、0.9、1.2、1.5gのソルビトールを加えて溶かした。ここに10%アスコルビン酸溶液1mlを混合し、冷蔵庫約10℃で1時間冷却した。その後、2時間、30℃に置いておくと、どの混合液も暗赤色ゲルになり、全体が固まった。ただし、ソルビトール1.2、1.5g混合したものは柔らかいゲルであった。糖の添加はゲルの形成を難しくするが、20重量%以上の濃度でもゲル化ができ、実用上問題がなかった。
実施例5のゲル1mlをメタノール10mlと混合し、遠心分離した。上澄みを捨て、メタノールを1ml加え、シャーレに入れ、減圧乾燥すると、シャーレ上にフィルムとして得られた。
実施例5のゲル1mlを2-プロパノール10mlと混合し、遠心分離した。上澄みを捨て、2-プロパノールを1ml加え、シャーレに入れ、減圧乾燥すると、シャーレ上にフィルムとして得られた。
実施例5のゲル4mlを濾紙No5上に入れ、吸引濾過した。2ープロパノール20mlで洗い、濾紙とともに減圧乾燥すると、濾紙に均一にコートされた。
比較例1の75℃で反応させた混合液を遠心分離して上澄みを捨てたのち、2-プロパノール 10mlで洗い、2-プロパノールを1ml加え、シャーレに入れ、減圧乾燥したが、結晶がシャーレの上に分散しており、フィルムにならなかった。
実施例5と同様にして調製した5g/Lの酸化型PQQジナトリウム溶液と4mlと10%アスコルビン酸溶液1mlを混合し、すぐに減圧乾燥した。混合直後に乾燥を始めた為、ゲル化が生じる前に水が蒸発した。そのため、粉末がまばらにあり、フィルムでなかった。
Claims (16)
- 還元型ピロロキノリンキノン誘導体またはその塩が、互いに会合して繊維状構造を形成していることを特徴とする、請求項1に記載のゲル。
- 還元型ピロロキノリンキノン誘導体またはその塩が、全ゲル重量に対して0.001~70重量%である、請求項1または2に記載のゲル。
- 還元型ピロロキノリンキノン誘導体またはその塩が、全ゲル重量に対して0.05重量%以上0.7重量%未満である、請求項1または2に記載のゲル。
- 還元剤をさらに含んでなる、請求項1~4のいずれか一項に記載のゲル。
- 分散媒が、水である、請求項1~5のいずれか一項に記載のゲル。
- 還元型ピロロキノリンキノン誘導体またはその塩が、全ピロロキノリンキノン誘導体またはその塩のモル数中に0.1モル%以上含まれる、請求項7に記載のゲル。
- 高分子ゲル化剤をさらに含んでなる、請求項1~8のいずれか一項に記載のゲル。
- 請求項1~9のいずれか一項に記載のゲルを乾燥した乾燥体。
- 請求項1~9のいずれか一項に記載のゲルから製造されたフィルム。
- 請求項1~9のいずれかに記載のゲルまたは請求項10に記載の乾燥体を含んでなる、食品。
- 請求項1~9のいずれかに記載のゲルまたは請求項10に記載の乾燥体を含んでなる、医薬。
- 請求項1~9のいずれかに記載のゲルまたは請求項10に記載の乾燥体を含んでなる、化粧品。
- 分散媒中の酸化型ピロロキノリンキノン誘導体またはその塩の濃度が、0.05重量%以上0.7重量%未満である、請求項15に記載の製造方法。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013544330A JP6052183B2 (ja) | 2011-11-15 | 2012-11-15 | 還元型ピロロキノリンキノンのゲル |
US13/261,856 US20150272881A1 (en) | 2011-11-15 | 2012-11-15 | Reduced pyrroloquinoline quinone gel |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011249341 | 2011-11-15 | ||
JP2011-249341 | 2011-11-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013073642A1 true WO2013073642A1 (ja) | 2013-05-23 |
Family
ID=48429696
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2012/079709 WO2013073642A1 (ja) | 2011-11-15 | 2012-11-15 | 還元型ピロロキノリンキノンのゲル |
Country Status (3)
Country | Link |
---|---|
US (1) | US20150272881A1 (ja) |
JP (1) | JP6052183B2 (ja) |
WO (1) | WO2013073642A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014175327A1 (ja) * | 2013-04-26 | 2014-10-30 | 三菱瓦斯化学株式会社 | 黄色系還元型ピロロキノリンキノン結晶及びその製造方法、並びに、食品、医薬品、ゲル、組成物及び組成物の製造方法 |
WO2018180885A1 (ja) * | 2017-03-28 | 2018-10-04 | 三菱瓦斯化学株式会社 | ピロロキノリンキノン含有ゼリー |
WO2020045562A1 (ja) * | 2018-08-30 | 2020-03-05 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンの安定化剤、それを含む組成物及び安定化方法 |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6825330B2 (ja) * | 2016-11-25 | 2021-02-03 | 三菱瓦斯化学株式会社 | オートファジー誘導剤 |
US20230210743A1 (en) * | 2022-01-04 | 2023-07-06 | Cao Group, Inc. | Dithionite shelf-stable sweeteners |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994001142A1 (en) * | 1992-07-06 | 1994-01-20 | The Children's Medical Center Corporation | Therapeutic compositions and methods using pqq |
JP2007269769A (ja) * | 2006-03-10 | 2007-10-18 | Ultizyme International Ltd | 神経変性疾患関連蛋白質凝集線維化抑制剤 |
WO2011102387A1 (ja) * | 2010-02-16 | 2011-08-25 | 三菱瓦斯化学株式会社 | 還元型ピロロキノリンキノンの製造方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011030485A (ja) * | 2009-07-31 | 2011-02-17 | Mitsubishi Gas Chemical Co Inc | 金属イオンを使用するピロロキノリンキノン類の製造方法 |
WO2012020767A1 (ja) * | 2010-08-09 | 2012-02-16 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンのゲル |
JP2012097020A (ja) * | 2010-11-01 | 2012-05-24 | Mitsubishi Gas Chemical Co Inc | 一重項酸素の消去方法 |
-
2012
- 2012-11-15 JP JP2013544330A patent/JP6052183B2/ja active Active
- 2012-11-15 WO PCT/JP2012/079709 patent/WO2013073642A1/ja active Application Filing
- 2012-11-15 US US13/261,856 patent/US20150272881A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994001142A1 (en) * | 1992-07-06 | 1994-01-20 | The Children's Medical Center Corporation | Therapeutic compositions and methods using pqq |
JP2007269769A (ja) * | 2006-03-10 | 2007-10-18 | Ultizyme International Ltd | 神経変性疾患関連蛋白質凝集線維化抑制剤 |
WO2011102387A1 (ja) * | 2010-02-16 | 2011-08-25 | 三菱瓦斯化学株式会社 | 還元型ピロロキノリンキノンの製造方法 |
Non-Patent Citations (1)
Title |
---|
DUINE,J.A. ET AL.: "Characterization of the second prosthetic group in methanol dehydrogenase from hyphomicrobium X", EUR J BIOCHEM, vol. 118, no. 2, 1981, pages 395 - 399 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014175327A1 (ja) * | 2013-04-26 | 2014-10-30 | 三菱瓦斯化学株式会社 | 黄色系還元型ピロロキノリンキノン結晶及びその製造方法、並びに、食品、医薬品、ゲル、組成物及び組成物の製造方法 |
US9732079B2 (en) | 2013-04-26 | 2017-08-15 | Mitsubishi Gas Chemical Company, Inc. | Yellow reduced pyrroloquinoline quinone crystal and method of producing the same, and food, pharmaceutical, gel, composition and method of producing composition |
WO2018180885A1 (ja) * | 2017-03-28 | 2018-10-04 | 三菱瓦斯化学株式会社 | ピロロキノリンキノン含有ゼリー |
JPWO2018180885A1 (ja) * | 2017-03-28 | 2020-02-06 | 三菱瓦斯化学株式会社 | ピロロキノリンキノン含有ゼリー |
JP7167911B2 (ja) | 2017-03-28 | 2022-11-09 | 三菱瓦斯化学株式会社 | ピロロキノリンキノン含有ゼリー |
WO2020045562A1 (ja) * | 2018-08-30 | 2020-03-05 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンの安定化剤、それを含む組成物及び安定化方法 |
JPWO2020045562A1 (ja) * | 2018-08-30 | 2021-08-12 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンの安定化剤、それを含む組成物及び安定化方法 |
JP7377442B2 (ja) | 2018-08-30 | 2023-11-10 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンの安定化剤及び安定化方法 |
Also Published As
Publication number | Publication date |
---|---|
JPWO2013073642A1 (ja) | 2015-04-02 |
JP6052183B2 (ja) | 2016-12-27 |
US20150272881A1 (en) | 2015-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5884731B2 (ja) | ピロロキノリンキノンのゲル | |
JP6052183B2 (ja) | 還元型ピロロキノリンキノンのゲル | |
Yi et al. | Preparation of strong antioxidative, therapeutic nanoparticles based on amino acid-induced ultrafast assembly of tea polyphenols | |
Sarkar et al. | Carbon quantum dot tailored calcium alginate hydrogel for pH responsive controlled delivery of vancomycin | |
Huang et al. | Preparation of inclusion complex of apigenin-hydroxypropyl-β-cyclodextrin by using supercritical antisolvent process for dissolution and bioavailability enhancement | |
Zuccari et al. | Formulation strategies to improve oral bioavailability of ellagic acid | |
Celebioglu et al. | Encapsulation and stabilization of α-lipoic acid in cyclodextrin inclusion complex electrospun nanofibers: Antioxidant and fast-dissolving α-lipoic acid/cyclodextrin nanofibrous webs | |
WO2020199349A1 (zh) | 一种纳米孔道型天然缓控释载体材料及制备方法 | |
CN104873983A (zh) | 一种姜黄素环糊精包合物及其制备方法 | |
Hou et al. | Mucoadhesive microparticles for gastroretentive delivery: preparation, biodistribution and targeting evaluation | |
CN103830744B (zh) | 一种缓释型鞣花酸-环糊精复合物及其制备方法 | |
Han et al. | Surfactant-free amorphous solid dispersion with high dissolution for bioavailability enhancement of hydrophobic drugs: a case of quercetin | |
Wu et al. | Amorphous silibinin nanoparticles loaded into porous starch to enhance remarkably its solubility and bioavailability in vivo | |
Du et al. | Organic solvent-free starch-based green electrospun nanofiber mats for curcumin encapsulation and delivery | |
Zhao et al. | Cyclodextrin-based metal-organic framework materials: Classifications, synthesis strategies and applications in variegated delivery systems | |
Wang et al. | Fabrication of hesperetin/hydroxypropyl-β-cyclodextrin complex nanoparticles for enhancement of bioactivity using supercritical antisolvent technology | |
García et al. | Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms | |
Ribeiro et al. | Cashew apple pectin as a carrier matrix for mangiferin: Physicochemical characterization, in vitro release and biological evaluation in human neutrophils | |
Dubey et al. | Nanostructured lipid carriers of ivabradine hydrochloride: optimization, characterization and in-vivo estimation for management of stable angina | |
CN104045679B (zh) | 甘草次酸晶c型、其制备方法及其在药物组合物或保健品中的用途 | |
Jeyaprakash et al. | Revealing the in vitro cytotoxicity potential of chitosan-mediated SiO2/ZnO nanocomposites on the human MCF-7 cell line | |
JP2003061593A (ja) | プロポリス組成物及びその顆粒製剤 | |
CN113082219B (zh) | 一种基于π-π作用的疏水药物的增溶方法 | |
JP6348024B2 (ja) | 水分散性の良いシリマリン含有組成物 | |
Heng et al. | Insights into Cocrystallization and Coamorphization Engineering Techniques in the Delivery of Traditional Chinese Medicine: Formation Mechanism, Solid-State Characterization, and Improved Pharmaceutical Properties |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 12850254 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2013544330 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13261856 Country of ref document: US |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 12850254 Country of ref document: EP Kind code of ref document: A1 |