CN105143428A - 酒精饮料中降低的毒性 - Google Patents
酒精饮料中降低的毒性 Download PDFInfo
- Publication number
- CN105143428A CN105143428A CN201480023673.7A CN201480023673A CN105143428A CN 105143428 A CN105143428 A CN 105143428A CN 201480023673 A CN201480023673 A CN 201480023673A CN 105143428 A CN105143428 A CN 105143428A
- Authority
- CN
- China
- Prior art keywords
- alcohol
- potenlini
- liver
- sugar
- pearlitol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 235000013334 alcoholic beverage Nutrition 0.000 title claims abstract description 50
- 230000001988 toxicity Effects 0.000 title claims abstract description 11
- 231100000419 toxicity Toxicity 0.000 title claims abstract description 11
- 230000002829 reductive effect Effects 0.000 title abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 108
- 239000000203 mixture Substances 0.000 claims abstract description 55
- 150000005846 sugar alcohols Chemical class 0.000 claims abstract description 32
- 235000000346 sugar Nutrition 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 17
- 210000004185 liver Anatomy 0.000 claims description 54
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 52
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 25
- 230000009467 reduction Effects 0.000 claims description 23
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 21
- HEBKCHPVOIAQTA-NGQZWQHPSA-N d-xylitol Chemical compound OC[C@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-NGQZWQHPSA-N 0.000 claims description 13
- 229960003487 xylose Drugs 0.000 claims description 13
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 12
- 229960004793 sucrose Drugs 0.000 claims description 12
- 239000004278 EU approved seasoning Substances 0.000 claims description 11
- 235000011194 food seasoning agent Nutrition 0.000 claims description 11
- 230000002443 hepatoprotective effect Effects 0.000 claims description 11
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims description 10
- -1 D-wood sugar Chemical compound 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 claims description 9
- 230000001154 acute effect Effects 0.000 claims description 8
- GZCGUPFRVQAUEE-KVTDHHQDSA-N aldehydo-D-mannose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-KVTDHHQDSA-N 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 231100000334 hepatotoxic Toxicity 0.000 claims description 8
- 230000003082 hepatotoxic effect Effects 0.000 claims description 8
- 239000003002 pH adjusting agent Substances 0.000 claims description 7
- 231100000240 steatosis hepatitis Toxicity 0.000 claims description 7
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 230000007863 steatosis Effects 0.000 claims description 4
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 3
- 240000009088 Fragaria x ananassa Species 0.000 claims description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000019634 flavors Nutrition 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
- 230000007665 chronic toxicity Effects 0.000 claims description 2
- 231100000160 chronic toxicity Toxicity 0.000 claims description 2
- 238000013016 damping Methods 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 239000004302 potassium sorbate Substances 0.000 claims description 2
- 229940069338 potassium sorbate Drugs 0.000 claims description 2
- 235000010241 potassium sorbate Nutrition 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 239000008371 vanilla flavor Substances 0.000 claims 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 abstract description 26
- 231100000304 hepatotoxicity Toxicity 0.000 abstract description 10
- 239000008367 deionised water Substances 0.000 abstract description 5
- 229910021641 deionized water Inorganic materials 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- LPLVUJXQOOQHMX-IOHDZAKGSA-N (2s,3s,4s,5r,6r)-6-[(2s,3r,4s,5s,6s)-2-[[(3s,4ar,6ar,6bs,8as,11s,12as,14ar,14bs)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1h-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-c Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-IOHDZAKGSA-N 0.000 abstract 2
- 150000008163 sugars Chemical class 0.000 abstract 2
- 206010019851 Hepatotoxicity Diseases 0.000 abstract 1
- 230000007686 hepatotoxicity Effects 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 description 77
- 239000000243 solution Substances 0.000 description 37
- 229940032362 superoxide dismutase Drugs 0.000 description 31
- 102000019197 Superoxide Dismutase Human genes 0.000 description 30
- 108010012715 Superoxide dismutase Proteins 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 27
- 102000016938 Catalase Human genes 0.000 description 25
- 108010053835 Catalase Proteins 0.000 description 25
- 241000700159 Rattus Species 0.000 description 23
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 22
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 22
- 229930195725 Mannitol Natural products 0.000 description 22
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 22
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 22
- 210000003494 hepatocyte Anatomy 0.000 description 22
- 239000000594 mannitol Substances 0.000 description 22
- 235000010355 mannitol Nutrition 0.000 description 22
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 20
- 230000001681 protective effect Effects 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 108010082126 Alanine transaminase Proteins 0.000 description 17
- 230000001476 alcoholic effect Effects 0.000 description 17
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 16
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 16
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 16
- 235000013361 beverage Nutrition 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 15
- 108090000790 Enzymes Proteins 0.000 description 15
- 229940088598 enzyme Drugs 0.000 description 15
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 14
- 239000012470 diluted sample Substances 0.000 description 13
- 230000036541 health Effects 0.000 description 13
- 230000004060 metabolic process Effects 0.000 description 13
- 230000000474 nursing effect Effects 0.000 description 13
- 239000004386 Erythritol Substances 0.000 description 12
- 239000003963 antioxidant agent Substances 0.000 description 12
- 229940009714 erythritol Drugs 0.000 description 12
- 230000006698 induction Effects 0.000 description 12
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 11
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 11
- 239000000811 xylitol Substances 0.000 description 11
- 235000010447 xylitol Nutrition 0.000 description 11
- 229960002675 xylitol Drugs 0.000 description 11
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 10
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 10
- 230000003078 antioxidant effect Effects 0.000 description 10
- 235000019414 erythritol Nutrition 0.000 description 10
- 230000007056 liver toxicity Effects 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 235000006708 antioxidants Nutrition 0.000 description 8
- 230000006907 apoptotic process Effects 0.000 description 8
- 210000005229 liver cell Anatomy 0.000 description 8
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 8
- 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 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- 230000008859 change Effects 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 230000036542 oxidative stress Effects 0.000 description 7
- 230000002195 synergetic effect Effects 0.000 description 7
- JVJFIQYAHPMBBX-UHFFFAOYSA-N 4-hydroxynonenal Chemical compound CCCCCC(O)C=CC=O JVJFIQYAHPMBBX-UHFFFAOYSA-N 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 229960004949 glycyrrhizic acid Drugs 0.000 description 6
- 235000019410 glycyrrhizin Nutrition 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229950006238 nadide Drugs 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) 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](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 5
- 229930003427 Vitamin E Natural products 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 235000019165 vitamin E Nutrition 0.000 description 5
- 229940046009 vitamin E Drugs 0.000 description 5
- 239000011709 vitamin E Substances 0.000 description 5
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 4
- 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 4
- 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 4
- 206010019668 Hepatic fibrosis Diseases 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 206010067125 Liver injury Diseases 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- CWHJIJJSDGEHNS-MYLFLSLOSA-N Senegenin Chemical compound C1[C@H](O)[C@H](O)[C@@](C)(C(O)=O)[C@@H]2CC[C@@]3(C)C(CC[C@]4(CCC(C[C@H]44)(C)C)C(O)=O)=C4[C@@H](CCl)C[C@@H]3[C@]21C CWHJIJJSDGEHNS-MYLFLSLOSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 4
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 4
- WQZGKKKJIJFFOK-PQMKYFCFSA-N alpha-D-mannose Chemical compound OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-PQMKYFCFSA-N 0.000 description 4
- SRBFZHDQGSBBOR-LECHCGJUSA-N alpha-D-xylose Chemical compound O[C@@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-LECHCGJUSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- XMOCLSLCDHWDHP-IUODEOHRSA-N epi-Gallocatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-IUODEOHRSA-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
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 4
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 4
- 231100000753 hepatic injury Toxicity 0.000 description 4
- 210000004024 hepatic stellate cell Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 210000001865 kupffer cell Anatomy 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 230000003859 lipid peroxidation Effects 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 229960002920 sorbitol Drugs 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000009871 tenuigenin Substances 0.000 description 4
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 4
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 3
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 3
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 3
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 3
- 241001539473 Euphoria Species 0.000 description 3
- 206010015535 Euphoric mood Diseases 0.000 description 3
- 208000004930 Fatty Liver Diseases 0.000 description 3
- 108010053070 Glutathione Disulfide Proteins 0.000 description 3
- 206010019708 Hepatic steatosis Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- ZSBXGIUJOOQZMP-JLNYLFASSA-N Matrine Chemical compound C1CC[C@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-JLNYLFASSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108010057466 NF-kappa B Proteins 0.000 description 3
- 102000003945 NF-kappa B Human genes 0.000 description 3
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 3
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 3
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 3
- 244000290333 Vanilla fragrans Species 0.000 description 3
- 235000009499 Vanilla fragrans Nutrition 0.000 description 3
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 230000005779 cell damage Effects 0.000 description 3
- 208000037887 cell injury Diseases 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- SPPIIOPGDLITJE-VLQRKCJKSA-N diazanium;(2s,3s,4s,5r,6s)-6-[[(3s,4ar,6ar,6bs,8as,11s,12ar,14ar,14bs)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1h-picen-3-yl]oxy]-5-[(2r,3r,4s,5s,6s)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy-3,4-dihy Chemical compound N.N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O SPPIIOPGDLITJE-VLQRKCJKSA-N 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 208000010706 fatty liver disease Diseases 0.000 description 3
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 3
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 3
- 229960001855 mannitol Drugs 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 108010033145 microsomal ethanol-oxidizing system Proteins 0.000 description 3
- 230000008811 mitochondrial respiratory chain Effects 0.000 description 3
- UMFJAHHVKNCGLG-UHFFFAOYSA-N n-Nitrosodimethylamine Chemical compound CN(C)N=O UMFJAHHVKNCGLG-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 235000005875 quercetin Nutrition 0.000 description 3
- 229960001285 quercetin Drugs 0.000 description 3
- 239000002516 radical scavenger Substances 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 235000018991 trans-resveratrol Nutrition 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 2
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 description 2
- LSHVYAFMTMFKBA-TZIWHRDSSA-N (-)-epicatechin-3-O-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=CC=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-TZIWHRDSSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 2
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 102000003849 Cytochrome P450 Human genes 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 2
- 244000303040 Glycyrrhiza glabra Species 0.000 description 2
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 2
- 239000004378 Glycyrrhizin Substances 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- ZSBXGIUJOOQZMP-UHFFFAOYSA-N Isomatrine Natural products C1CCC2CN3C(=O)CCCC3C3C2N1CCC3 ZSBXGIUJOOQZMP-UHFFFAOYSA-N 0.000 description 2
- XMOCLSLCDHWDHP-UHFFFAOYSA-N L-Epigallocatechin Natural products OC1CC2=C(O)C=C(O)C=C2OC1C1=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-UHFFFAOYSA-N 0.000 description 2
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 2
- 102100031455 NAD-dependent protein deacetylase sirtuin-1 Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010041191 Sirtuin 1 Proteins 0.000 description 2
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 201000007930 alcohol dependence Diseases 0.000 description 2
- 229960002478 aldosterone Drugs 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 231100000315 carcinogenic Toxicity 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229960003720 enoxolone Drugs 0.000 description 2
- DZYNKLUGCOSVKS-UHFFFAOYSA-N epigallocatechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3cc(O)c(O)c(O)c3 DZYNKLUGCOSVKS-UHFFFAOYSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- 229930182478 glucoside Natural products 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 239000001685 glycyrrhizic acid Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 229930014456 matrine Natural products 0.000 description 2
- 239000002395 mineralocorticoid Substances 0.000 description 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 238000005502 peroxidation Methods 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 210000004500 stellate cell Anatomy 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000009278 visceral effect Effects 0.000 description 2
- 235000019155 vitamin A Nutrition 0.000 description 2
- 239000011719 vitamin A Substances 0.000 description 2
- 235000019156 vitamin B Nutrition 0.000 description 2
- 239000011720 vitamin B Substances 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 229940045997 vitamin a Drugs 0.000 description 2
- 229940046001 vitamin b complex Drugs 0.000 description 2
- 235000013522 vodka Nutrition 0.000 description 2
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 1
- 102000003952 Caspase 3 Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 108010001202 Cytochrome P-450 CYP2E1 Proteins 0.000 description 1
- 102100024889 Cytochrome P450 2E1 Human genes 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical group O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- LSHVYAFMTMFKBA-UHFFFAOYSA-N ECG Natural products C=1C=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-UHFFFAOYSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 102100027186 Extracellular superoxide dismutase [Cu-Zn] Human genes 0.000 description 1
- 108700001268 Extracellular superoxide dismutase [Cu-Zn] Proteins 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 229930091371 Fructose Natural products 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
- 239000005715 Fructose Substances 0.000 description 1
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 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
- 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 1
- 206010018873 Haemoconcentration Diseases 0.000 description 1
- 238000012752 Hepatectomy Methods 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 206010019837 Hepatocellular injury Diseases 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 229930195498 Hovenine Natural products 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020852 Hypertonia Diseases 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
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- LKDRXBCSQODPBY-NSHGFSBMSA-N L-fructose Chemical compound OCC1(O)OC[C@H](O)[C@H](O)[C@H]1O LKDRXBCSQODPBY-NSHGFSBMSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 101100139957 Mus musculus Rb1cc1 gene Proteins 0.000 description 1
- 102000003896 Myeloperoxidases Human genes 0.000 description 1
- 108090000235 Myeloperoxidases Proteins 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 102000009339 Proliferating Cell Nuclear Antigen Human genes 0.000 description 1
- 101000648290 Rattus norvegicus Tumor necrosis factor Proteins 0.000 description 1
- 244000039545 Salacia macrophylla Species 0.000 description 1
- 206010041277 Sodium retention Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 102000018594 Tumour necrosis factor Human genes 0.000 description 1
- 108050007852 Tumour necrosis factor Proteins 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- LPQOADBMXVRBNX-UHFFFAOYSA-N ac1ldcw0 Chemical compound Cl.C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3CCSC1=C32 LPQOADBMXVRBNX-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 231100000085 chronic toxic effect Toxicity 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 229920002770 condensed tannin Polymers 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000007323 disproportionation reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- WGXUDTHMEITUBO-YFKPBYRVSA-N glutaurine Chemical compound OC(=O)[C@@H](N)CCC(=O)NCCS(O)(=O)=O WGXUDTHMEITUBO-YFKPBYRVSA-N 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 206010019692 hepatic necrosis Diseases 0.000 description 1
- 230000007866 hepatic necrosis Effects 0.000 description 1
- 231100000437 hepatocellular injury Toxicity 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical compound O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
- 208000018875 hypoxemia Diseases 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000006676 mitochondrial damage Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000003614 peroxisome proliferator Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 210000004258 portal system Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 235000015041 whisky Nutrition 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
- C12G3/00—Preparation of other alcoholic beverages
- C12G3/04—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
- C12G3/05—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with health-improving ingredients, e.g. flavonoids, flavones, polyphenols or polysaccharides
- C12G3/055—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with health-improving ingredients, e.g. flavonoids, flavones, polyphenols or polysaccharides extracted from plants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
- C12G3/00—Preparation of other alcoholic beverages
- C12G3/04—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
- C12G3/06—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with flavouring ingredients
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Botany (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Physiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Distillation Of Fermentation Liquor, Processing Of Alcohols, Vinegar And Beer (AREA)
- Alcoholic Beverages (AREA)
- Non-Alcoholic Beverages (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及功能性酒精饮料组合物的降低的毒性,所述功能性酒精饮料组合物包含蒸馏酒精、去离子水、18β-甘草酸或18α-甘草酸以及糖醇或糖,所述功能性酒精饮料组合物具有4.0-9.0的范围内的pH。更特别地,酒精饮料组合物包含蒸馏酒精、去离子水、作为肝保护剂的18β-甘草酸或18α-甘草酸以及糖醇/糖。本发明提供用于降低由酒精饮料的消耗引起的肝毒性的酒精饮料和制造所述酒精饮料的工艺。
Description
以下说明书特别地描述本发明和本发明被进行的方式。
发明领域
本公开内容提供具有降低的肝毒性的酒精饮料。本发明还涉及用于制备所述饮料的工艺。
发明背景
乙醇消耗可以导致60种医疗状况。乙醇的急性以及慢性毒性作用可以引发不可逆的器官损伤(DasS.K.等人,IndianJournalofBiochemistry&Biophysics,2010,第47卷,32)。酒精性肝病(ALD)的广泛接受的形式是单纯性脂肪肝(脂肪变性),其是随着节制可逆的,伴随炎症的脂肪肝(脂肪性肝炎)导致瘢痕组织形成(纤维化)、正常肝结构的破坏(肝硬化),其可以或可以不随着节制改善并且随后导致肝癌(肝细胞癌)。在2010年,WHO提出在美国10%的成人人群罹患酒精使用紊乱并且肝硬化在美国是第12主要死亡原因(AlcoholandHealth,Focuson:AlcoholandtheLiver,2010,第33卷,第1和2期,87)。已知人类摄取的5%的乙醇(ethylalcohol)即乙醇(ethanol)(下文中酒精)被未改变地排泄,然而剩下的95%被降解成乙醛。酒精从胃肠道被快速吸收。在禁食状态中,峰值血液酒精浓度在30分钟内达到。分布是快速的,且组织水平接近血液浓度。肝负责近90%的酒精代谢,其余通过肺&尿被排泄。典型的成人可以代谢7-10g的酒精/小时(美国专利第7666909B2号)。
酒精代谢的主要路径,当以低至中度的量被消耗时,主要在肝细胞的细胞质中被醇脱氢酶(ADH)催化以形成乙醛。NADH在肝中的累积(过量还原当量)随着慢性酒精使用在更显著见到的肝损伤中起作用。通过微粒体乙醇氧化系统(MEOS)产生的乙醛初始地代表可能地解释小于10%的肝氧化乙醇的能力的乙醇氧化的次要路径。
在较高酒精水平(>100mg/dl)下,MEOS取决于使用NADH作为辅因子&O2在酒精代谢中起重要作用的CYP450(2E1,1A2&3A4)。在禁食状态中,在过氧化氢产生系统存在下过氧化氢酶尤其能够氧化乙醇。乙醛在肝中经由线粒体烟酰胺腺嘌呤二核苷酸(NAD+)依赖性醛脱氢酶(ALDH)被氧化成乙酸盐。ALDH的活性比ADH低近3倍,因此发生乙醛的累积。乙酸盐被进一步代谢成乙酰CoA并且可以进入TCA循环或合成脂肪酸。这些路径中的每个随着细胞氧化还原状态中伴随的变化导致自由基的形成(像活性氧{ROS})(即,NADH与NAD+的比率导致产生更多NADH(被两个电子还原的烟酰胺腺嘌呤二核苷酸(NAD+))。在线粒体呼吸链中在确定反应的动力学的此系统的最大能力下,细胞具有使NADH氧化回至NAD+的限制的能力。与酒精代谢相关的氧化还原状态引起对肝细胞的正常代谢是典型的NAD+介导的酶反应的抑制。柠檬酸循环是最受影响的,因为其受到抑制。这导致正的NADH/NAD比率,其被认为是酒精诱导的脂肪肝的发展的最重要的原因。线粒体呼吸链的最大能力取决于身体代谢的总体水平。改变的氧化还原状态的结果包括低氧(缺氧细胞)。酒精诱导的肝毒性的其他合理的路径包括通过肠内毒素刺激的枯否细胞过量产生促炎症细胞因子。ROS主要与线粒体电子传递系统相关地产生;其在肝中也由CYP2E1和由激活的枯否细胞产生。急性和慢性酒精消耗两者均可以提高ROS产生,ROS产生通过以上提及的多种路径导致氧化应激[(Zakhari,S.AlcoholResearch&Health,2006,29,4,245),(WheelerM.D.等人,FreeRadicalBiology&Medicine,2001,第31卷,第12期,1544),(Koop,D.R.,AlcoholResearch&Health,2006,29,4,274),(美国专利第7666909B2号)]。
酒精引起细胞损伤的涉及的机制是若干互相关联的路径的复合和组合。ROS主要与细胞膜反应(紧密的连接变得更可渗透的)并且进而渗漏脂多糖(LPS),结果损害肠道结构的完整性。转氨酶[天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)]的提高指示细胞渗漏和细胞膜的功能性完整性的损失(Yue等人,2006)。细胞完整性的损失影响肝胆功能,导致提高的碱性磷酸酶(ALKP)活性,且同时血清胆红素水平升高并且总血浆蛋白含量降低。ROS的水平的升高和降低两者均可以导致肝细胞的细胞凋亡(WheelerM.D.AlcoholRes.Health,2003;27,300)。对于正常地起作用的细胞,GSH对于保护自身免受在线粒体呼吸链的活动期间产生的ROS是重要的。酒精消耗快速耗尽GSH水平;酒精干扰细胞色素c以从线粒体渗漏到细胞质内,其可以激活被称为可以引发细胞凋亡的半胱天冬酶的酶。
ROS诱导LPO[ROS与丙二醛(MDA)、4-羟基壬烯醛(HNE)反应]并且被认为是肝细胞损伤的重要的起始点。内毒素激活的枯否细胞影响线粒体,导致释放ROS(过氧化氢自由基、羟基自由基、特别地超氧化物自由基)和若干细胞因子(也就是,肿瘤坏死因子{TNF-α}),导致肝细胞坏死和凋亡。已经通过临床研究建立的是,具有酒精性肝病的患者具有炎症性细胞因子IL-1、IL-6、和TNF-α以及趋化因子IL-8和其他细胞因子的提高的水平。
酒精可以提高肝细胞的敏感性,这因此可以导致线粒体中ROS的提高的产生。ROS可以激活称为核因子κB(NFκB)的调节蛋白,其在调节免疫应答中起关键作用并且控制大量基因的活动,包括表达TNF-α&其受体以及促进细胞凋亡的基因编码蛋白的活动。因此,恶性循环将在肝细胞中建立:TNF-α促进ROS产生,这进而激活NFκB,导致另外的TNF-α和其受体的提高的产生以及导致促进细胞凋亡的因子的产生。此循环最终改变肝细胞的结构,损害其功能,并且可以导致肝细胞凋亡。TNF-α还通过促进增殖有助于肝细胞再生[(WheelerM.D.AlcoholResHealth,2003;27,300),(MolinaP.,Happel,K.I.,ZhangP.,KollsJ.K.,NelsonS.,Focuson:alcoholandtheimmunesystem.AlcoholRes.Health,2010,33(1&2),97)1)]。
TGF-β(转化生长因子β)可以参与酒精诱导的肝损伤的形成,这可以引起肝细胞产生通常负责给予细胞其形状的像转谷氨酰胺酶、细胞角蛋白的分子。过量地,这些分子交联以形成称为马洛里小体的显微结构,其是酒精性肝炎的标志物。TGF-β还可以通过激活星形细胞促进肝损伤。在正常状态中,这些细胞主要用来在肝中储存脂肪和维生素A。当被激活时,星形细胞产生胶原蛋白,瘢痕组织的主要组分,其导致肝纤维化的形成。酒精可以引发TGF-β的激活并且从而有助于细胞凋亡的开始,如果此分子以较高浓度进入血液(WheelerM.D.,AlcoholRes.Health,2003;27,300)。
在细胞中,乙醛或ROS与DNA或蛋白或蛋白构件和ROS与MDA或MAA(混合的MDA-乙醛-蛋白加合物)或HNE等可以形成稳定的或不稳定的加合物,所述加合物可以是致癌的、免疫原性的,诱导炎症过程、对线粒体的损伤等[(Zakhari,S.AlcoholResearch&Health,2006,29(4)245);(D.Wu,AlcoholResearch&Health,2006,27,4,277);(WheelerM.D.,AlcoholRes.Health,2003;27,300);(MolinaP.,HappelK.I.,ZhangP.,KollsJ.K.,NelsonS.,Focuson:alcoholandtheimmunesystem;(AlcoholRes.Health,2010,33,第1&2卷,97);(NeumanM.G.,Cytokine-centralfactorinalcoholicliverdisease,AlcoholRes.Health,2003,27,307)]。
多种内源性酶促的或非酶促的机制已经发展以保护细胞抵抗ROS。这包括移除O2 -的超氧化物歧化酶(SOD);移除H2O2的过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPX)系统和诸如还原的谷胱甘肽(GSH)、维生素E、维生素C、维生素A、泛醌、尿酸和胆红素的非酶促低分子量抗氧化剂。但这些能够在受限制的程度上保护细胞。可以通过口服施用像S-腺苷-L-甲硫氨酸(SAMe)、N-乙酰基半胱氨酸(NAC)的谷胱甘肽前体或像维生素E、维生素C、植物生物活性物(没食子酸、槲皮素等)等的抗氧化剂实现另外的保护(D.Wu,AlcoholResearch&Health,2006,27,4,277)。
本发明现有技术
文献公开具有多种类型的添加剂的酒精饮料。以下文献存在于本发明的领域中并且已经以其整体被考虑。
美国专利公布第20100086666号公开酒精饮料,其中像酪蛋白的蛋白水解以提高较顺口的味道并且向消费者给出某些营养益处。
DasS.K.等人(IndianJournalofBiochemistry&Biophysics,2010,第47卷,32)描述白藜芦醇或维生素E与酒精的联合治疗在小鼠中改善酒精诱导的氧化应激、血管生成过程并且帮助控制免疫调节活性。
美国专利公布第20100086666号公开酒精饮料,其包含像表没食子儿茶素没食子酸酯(EGCG)、表没食子儿茶素(EGC)、表儿茶素(EC)、表儿茶素没食子酸酯(ECG)、前花青素、鞣酸以及槲皮素等的酚,所述酚已知通过清除由酒精产生的自由基来降低氧化应激。
美国专利公布第7666909B2号揭示包含D-甘油酸和其盐的酒精饮料,其提高酒精的代谢,降低由于酒精消耗引起的不良事件。
从苦参(S.flavescens)分离的单独的GA或苦参碱(Mat)生物碱,或GA+Mat,当被施用到在对乙酰氨基酚过剂量的小鼠中通过腹腔注射二甲基亚硝胺(DMN)诱导的肝纤维化的大鼠模型时,通过减弱对乙酰氨基酚诱导的肝毒性减低死亡率。这可能是由于γ-GT阳性灶的降低的数目和面积。此外,GA+Mat对免疫抑制具有保护性作用即强烈的非特异性抗炎作用并且具有降低钠和水潴留的发生率的作用(W.Xu-yingae,Chemico-BiologicalInteractions.181(2009)15-19)。
世界专利第2008/055348A1号公开包含降低宿醉的姜黄的酒精饮料。
DasS.K.等人(IndianJournalofExperimentalBiology,2006,第44卷,791)揭示在维斯塔大鼠中进行卵磷脂与维生素B复合物或维生素E与酒精的联合治疗。建立的是,相比于维生素E与酒精,卵磷脂与维生素B复合物与酒精在减轻氧化应激中是有前景的治疗方法。
El-FazaaS.等人(Alcoholism&Alcoholism,2006,第41卷,第3期,236)例示包含白藜芦醇的酒精饮料抑制酒精诱导的脂质过氧化作用并且具有抵抗损伤的保护性作用。
WO1989004165A1或EP0336960A4公开具有来自由以下组成的组的任何一种或更多种糖的组合的酒精饮料:D-半乳糖、D-乳糖、D-木糖、L-果糖、D-甘露醇、D-山梨糖醇、D-葡萄糖等。
JP06014746公开包含槲皮素的糖苷、二价金属离子和甘草提取物(甘草酸)的酒精饮料。此饮料提高酒精代谢并且具有肝病抑制性活性,这归因于乙醇和乙醛。因此,其降低宿醉。
CP专利公布第1736270号公开由壳寡糖、甘草酸、葛花的水提取物以及枳椇碱(hovenine)的水提取物组成的护肝饮品。
美国专利公布第20090196951号揭示包含白藜芦醇(强抗氧化剂)的酒精饮料,还激活Sirtuin1(SIRT1)以及过氧化物酶体增殖物激活(PPAR)-γ共激活剂-1[PGC-l']基因,其是能量和代谢体内平衡的关键调节因子。
JP2008266203和EP0502554公开具有选自由赤藓糖醇、甘露醇、山梨糖醇和木糖醇组成的组的一种或更多种物质的诸如超氧化物歧化酶、过氧化氢酶或过氧化物酶的活性氧(ROS)清除酶组的酶活性的量的提高。
CN1448497公开包含乙醇和甘草酸的酒精饮品,但酒精与包括作为本组合物的组成部分的某些糖醇或糖的肝保护剂(除了甘草酸)的协同混合物,未曾被描述。
CN101744865公开产生包含木糖醇和甘草酸的护肝片剂的方法。CN101744865关注于用于制备木糖醇肝片剂的方法并且没有阐明这样的片剂的生物活性。此外,本专利关注于具有降低的毒性的酒精饮料以及其制备方法。本申请阐明酒精与作为组合物的组成部分的包括某些糖醇或糖的肝保护剂的协同混合物,并且这样的协同混合物提供良好程度的肝保护。
多种其他现有技术文献是已知的(US20080226787、US3282706、US1720329、US4537763、US8524785),其中甘草酸和像甘露醇、赤藓糖醇、木糖醇等的糖醇已经作为具有低热值的非营养性甜味剂或作为调味剂被用于在饮料中赋予多种功能,但肝保护的方面没有被公开。
文献在现有技术中是可得的,其示出甘草酸、糖醇和糖被独立地认为呈现肝保护性活性,但目前为止没有报道它们的组合呈现协同的肝保护作用。本申请中,申请人第一次报道由18β-甘草酸或18α-甘草酸和糖醇的组合赋予的协同活性,更特别地18β/α-甘草酸和D-甘露醇呈现示例性的协同肝保护作用以提供具有降低的毒性的饮料。
发明概述
本公开内容涉及酒精饮料,特别地涉及像伏特加、加味伏特加、威士忌等的酒精蒸馏酒,所述酒精饮料具有降低的肝毒性,包含蒸馏酒精、去离子水、甘草酸和糖醇或糖,具有在4.0-9.0的范围内的pH。
更特别地,本发明提供具有降低的肝毒性的酒精饮料,该酒精饮料包含蒸馏酒精、去离子水、18β-甘草酸或18α-甘草酸以及糖醇或糖。本发明还涉及用于制备所述饮料的工艺。由饮料提供的示例的降低的肝毒性已经通过由在所述酒精饮料中存在的18β-甘草酸或18α-甘草酸和糖醇/糖的组合呈现的协同肝保护作用来实现。
发明目的
本发明的目的是提供具有降低的毒性的酒精饮料。
本发明的另一个目的是提供具有协同活性并且提供提高的肝保护作用的酒精饮料。
本发明的又另一个目的是提供包含肝保护剂的饮料以实现降低的肝毒性。
本发明的又另一个目的是提供包含18β-甘草酸或18α-甘草酸的酒精饮料以实现降低的肝毒性。
本发明的又另一个目的是提供包含像糖醇和糖的肝保护剂的酒精饮料。
本发明的又另一个目的是提供包含选自D-甘露醇、D-赤藓糖醇、D-木糖醇及类似物的糖醇的酒精饮料。
本发明的又另一个目的是提供包含选自D-木糖、D-甘露糖、D-蔗糖和D-乳糖的糖的酒精饮料。
本发明的又另一个目的是提供包含pH调整剂、调味剂的酒精饮料。
本发明的另外的目的是提供任选地包含选自香草、草莓及类似物的调味剂的酒精饮料。
本发明的又另一个目的是提供具有可接受的味道、滋味、气味、透明度和陶醉感因素(buzzfactor)的酒精饮料。
本发明的另一个重要的目的是提供用于制备包含(a)酒精或酒精:水混合物(b)18β-甘草酸/18α-甘草酸(c)糖醇或糖(d)pH调整剂以及任选地调味剂的酒精饮料组合物的工艺。
本发明的又另一个目的提供具有提高的肝保护作用的酒精饮料组合物。
酒精饮料用于在缓解涉及急性和慢性酒精毒性的疾病如酒精性肝病(ALD)如脂肪变性的方法中使用。
表格简述:
表1:D-甘露醇的保护作用%
表2:D-木糖醇和D-赤藓糖醇的保护作用%
表3:18β-甘草酸和18α-甘草酸的比较保护作用%
表4:18β-甘草酸-甘露醇组合的保护作用%和协同作用%
表5:18β-甘草酸-甘露醇组合或18α-甘草酸-甘露醇组合的比较保护作用%和比较协同作用%
表6:18β-甘草酸-甘露醇、木糖醇&赤藓糖醇的比较保护作用%和比较协同作用%
表7:(18β-甘草酸/甘露醇、木糖醇&赤藓糖醇)的保护作用%和协同作用%的比较数据
表8:蔗糖、甘露糖、木糖&乳糖的保护作用%
表9:(18β-GA:蔗糖、甘露糖、木糖&乳糖)的保护作用%和协同作用%
发明详述
相应地,本发明提供饮料,更特定地具有降低的肝毒性的酒精饮料,该酒精饮料包含蒸馏酒精、去离子水、18β-甘草酸或18α-甘草酸以及糖醇或糖,具有4.0-9.0的范围内的pH。更特别地,肝毒性是由酒精的摄入引起的。本发明的饮料的降低的肝毒性通过由被包含在所述酒精饮料中的18β-甘草酸或18α-甘草酸和糖醇或甘草酸和糖的协同组合提供的提高的肝保护活性来实现。组分的协同作用已经通过在动物模型上进行实验的对18β-甘草酸或18α-甘草酸、糖醇以及甘草酸和糖醇/糖的组合的肝保护的剂量依赖性研究被建立。
成分描述:
甘草酸(Glycyrrhizin)(或甘草酸(Glycyrrhizicacid)或甘草酸(Glycyrrhizinicacid):缩写为GA)是光果甘草(Glycyrrhizaglabra)(甘草)根的主要甜味剂成分。其在日本已经被静脉内给予作为用于丙型肝炎的治疗并且在食品和化妆品中作为乳化剂和凝胶形成剂。甘草酸(GA)是三萜皂苷糖苷。其作为以2个异构体的外消旋或纯的形式是可用的:18β-甘草酸和18α-甘草酸。GA的肝保护机制是由于其糖苷配基,甘草次酸,甘草次酸抑制自由基的产生以及脂质过氧化二者。18α-GA具有抗肝纤维化作用-其频繁地被用作肝保护剂。GA的甜味具有比糖更慢的发作,并且在口中逗留一定时间。GA作为完整的药物被部分地吸收。(W.Xuyinga等人)Chemico-BiologicalInteractions181(2009)15-19)、(T,Zing等人,ChineseJournalofModernAppliedPharmacy2006,02,15-19)。GA和其代谢物呈现类似类固醇的抗炎活性,这部分地归因于抑制磷脂酶A2活性,一种对大量炎症过程关键的酶。其抑制醛固酮的肝代谢并且压制肝5-α-还原酶。因为皮质醇和醛固酮以相同的亲和力与盐皮质激素受体结合,肾皮质醇的提高将导致高盐皮质激素作用(Akamatsu,H.PlantaMed.,1991,57:119-121),(Armanini,D.,Clin.Endocrinol.1983,19:609)。
GA可能地通过引起细胞表面上负电荷的降低和/或通过降低膜流动性来完全地压制病毒抗原表达,从而通过受体介导的内吞作用防止甲型肝炎病毒进入细胞(W.Xu-Yinga等人,Chemico-BiologicalInteractions181(2009)15-19)。
GA诱导参与致癌的或毒性的物质的解毒和排泄的II相酶以及负责维持细胞环境内的自由基/氧化剂和抗氧化剂之间的平衡状态的其他抗氧化剂酶。在AR小鼠(醛糖还原酶缺乏小鼠)中的氧化性损伤通过GA、通过提高GSH含量并且以剂量依赖方式降低MDA形成来降低。在AR小鼠中,观察到谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)、总抗氧化剂能力(TAOC)和SOD活性的同时降低。IFN-α,或II型干扰素,是对于抵抗病毒和细胞内细菌感染的先天性和适应性免疫力并且对于肿瘤控制关键的细胞因子。GA导致药物治疗的小鼠中IFN-α水平的明显升高。IL-4是诱导初始辅助性T细胞(Th0细胞)分化成Th2细胞的细胞因子。在通过IL-4激活之后,Th2细胞随后产生另外的IL-4(Xiao-LanLiInt.J.Mol.Sci.2011,12,905)。GA可以提高感染抗性,因为[单核细胞化学吸附(趋化性)蛋白-1]是CC趋化因子MCP-1抑制剂(美国专利申请20060116337)。
将小鼠用CC14(0.5ml/kg)腹腔内地治疗。在施用CC14前24h和0.5h以及在施用CC14后4h,小鼠接受GA(50、300、200、400mg/kg)。这种保护作用可能是由于诱导血红素加氧酶-1并且下调促炎症介质(BiolPharmBull.2007,30,10,1898)。18α-GA可以剂量依赖性地抑制CC14诱导的肝纤维化,通过促进肝细胞的增殖,但抑制肝星状细胞(HSC)的增殖,GA阻断NF-κB转运到细胞核内;这可以压制HSC的激活并且诱导HSC的凋亡(QYing,MedSci.Monit.,2012,18,1:BR24)。
GA被示出在所有指示的时间减弱肝组织学改变并且明显降低AST、ALT和乳酸脱氢酶(LDH)的血清水平。GA还通过下调半胱天冬酶-3的表达并且抑制细胞色素c从线粒体释放到细胞质内来明显抑制肝细胞凋亡。GA的抗炎活性可以依赖于抑制肿瘤坏死因子α的释放、髓过氧化物酶活性和核因子κB到细胞核内的转运。GA还上调增殖细胞核抗原的表达,这意味着其可能能够促进被LPS损害的肝的再生。总之,GA可以代表保护肝免受内毒素诱导的损伤的有效药物,尤其在大面积肝切除术之后(BrazilianJournalofMedicalandBiologicalResearch,2007,40,1637)。在用LPS/GalN处理的小鼠中,用GA(50mg/kg)和MMP抑制剂(5mg/kg)的预治疗压制ALT和AST的血清水平的升高,这归因于下调MMP-9(JPharmPharmacol.2008,60,1,91)。
代谢综合征(MetS)是一组包括内脏型肥胖、脂代谢紊乱和胰岛素抗性(IR)的代谢异常。口服施用50mg/kg的GA持续一周可以抵消内脏型肥胖的发展并且分别通过选择性诱导组织脂蛋白酯酶(LPL)改进脂代谢紊乱、血清脂质参数中的表达和正位移,并且阻止与组织脂肪变性相关的IR的发展(LipidsHealthDis.2009,29,8,31)。
甘草酸二铵(DG)保护小鼠以抵抗刀豆蛋白A(ConA)诱导的血清ALT水平的提高以及肝细胞的凋亡;DG可能地可以通过两种路径保护肝免受损伤:通过IL-6依赖性方式直接保护肝细胞免受凋亡以及通过IL-1依赖性方式间接抑制T细胞介导的炎症(IntImmunopharmacol.200710月:7(10):1292)。
每天一次异甘草酸镁100mg或150mg,药物对于慢性肝病是有效的且安全的治疗(ZhoiighuaGanZangBingZaZhi.2009,11,847)。
糖醇是一种从糖制备的醇。这些有机化合物是一类多元醇,也称为多元醇(polyhydricalcohol)、多元醇(polyalcohol)或多羟糖醇(glycitol)。它们是天然存在的白色的、水溶性固体并且作为增稠剂和增甜剂被广泛地用于食品工业中。化学上稳定的糖醇,诸如甘露醇、赤藓糖醇、山梨糖醇、木糖醇等,可以被用作自由基(羟基自由基)清除剂。同样地,已经发现像赤藓糖醇、甘露醇、山梨糖醇、木糖醇等的化合物上调不同类型的超氧化物歧化酶(SOD),像Cu/Zn-、Mn-以及EC-SOD同工酶。特别地,添加赤藓糖醇的组的SOD活性提高了2-5倍。还报道了糖尿病具有低的SOD活性,由于美拉德反应,因为美拉德反应显著地引起SOD活性的降低(美国专利申请20100037353Al)。含有甘露醇的高渗性溶液已经被示出保护乙醇诱导的胃粘膜损伤(GharzouliK,Exp.Toxic.Pathol.,2001;53:175)。大鼠和人类二者部分地吸收和代谢在胃肠道(GIT)中摄取的甘露醇。然而,肠道微生物群落将甘露醇转化成更易吸收的形式。在大鼠中,吸收的甘露醇可能地经由果糖被转化成肝糖原(J.Nutr.1985,115:890)。通过甘露醇保护肝细胞的机制没有被完全地理解。
饮料包含像pH调整剂和调味剂等的某些其他成分。
本发明的饮料的某些重要的实施方案如下:
本发明的重要的实施方案涉及具有降低的毒性的饮料。
本发明的又另一个实施方案涉及具有降低的肝毒性的酒精饮料。
本发明的又另一个实施方案涉及包含实现降低的肝毒性的肝保护剂的酒精饮料。
在本发明的重要的实施方案中,饮料包含与选自由D-甘露醇、D-木糖醇、D-赤藓糖醇及其混合物组成的组的糖醇以及选自D-木糖、D-甘露糖、D-蔗糖和D-乳糖及其混合物的还原或非还原糖组合的18β-甘草酸。
在本发明的又另一个重要的实施方案中,饮料包含与选自由D-甘露醇、D-木糖醇、D-赤藓糖醇及其混合物组成的组的糖醇组合的18α-甘草酸。
在重要的实施方案中,饮料组合物包含在0.05%至0.4%、优选地0.1%至0.3%范围内的18β-甘草酸以及在0.5%至3.0%、优选地1.0%至2.5%范围内的D-甘露醇、D-木糖醇、D-赤藓糖醇、D-木糖、D-甘露糖、D-蔗糖、D-乳糖及其混合物。
在重要的实施方案中,饮料组合物包含在0.05%至0.3%、优选地0.1%至0.3%范围内的18α-甘草酸以及在0.5%至3.0%、优选地1.0%至2.5%范围内的D-甘露醇、D-木糖醇、D-赤藓糖醇及其混合物。
在重要的实施方案中,肝保护剂的最优选的组合是18β-甘草酸或18α-甘草酸和D-甘露醇的组合。
在重要的实施方案中,饮料组合物包含在0.05%至0.3%范围内的18β-甘草酸和在0.5%至3.0%范围内的D-甘露醇,并且优选地包含在0.1%至0.3%范围内的18β-甘草酸和在1.0%至2.5%范围内的D-甘露醇。
在重要的实施方案中,饮料组合物包含在0.1%至0.3%范围内的18α-甘草酸和在1.0%至2.5%范围内的D-甘露醇。
在又另一个实施方案中,用于制备酒精饮料组合物的工艺,包括以下的步骤:(a)获得酒精或水或其混合物,(b)使18β-甘草酸或18α-甘草酸与步骤(a)中的酒精或水或酒精和水的混合物混合,(c)将糖醇或糖添加至步骤(b)中的混合物,(d)将步骤(c)中获得的溶液的pH调整在4.0-9.0之间,(e)任选地添加调味剂及(f)获得要求的酒精饮料组合物。
本发明的还另一个实施方案是提供包含pH调整剂的酒精饮料组合物。
本发明的又另一个实施方案中,pH调整剂是有机或无机碱/缓冲液、优选地选自山梨酸钾或磷酸钠(单碱式或二碱式或三碱式)。
本发明的另外的实施方案提供任选地包含选自香草和草莓的调味剂的饮料。
本发明的还另一个实施方案是提供具有可接受的味道、滋味、气味、透明度和陶醉感因素的饮料。
在本发明的另外的实施方案中,糖醇、甘草酸以及糖醇和18β-甘草酸或18α-甘草酸的组合的剂量的变化也已经关于其肝保护性活性被评估。
本发明的范围还包括关于由酒精剂量的变化以及其在施用中的持续时间引起的急性和慢性肝毒性的研究。
该饮料组合物的还另一个实施方案涉及提供降低的肝毒性。
该饮料组合物的又另一个实施方案是在缓解涉及急性和慢性毒性的疾病诸如像由酒精诱导的毒性引起的脂肪变性、脂肪性肝炎、纤维化、肝硬化和肝细胞癌等的酒精性肝病(ALD)的方法中的使用。
本发明的另一个重要的实施方案是饮料组合物可以被包装为在食品级瓶、罐、四角包装、袋中的即饮产品。包装可以通过常规的方法来完成。
对于本发明的制剂中存在的协同作用的建立,标志物/标志酶,也就是SOD、过氧化氢酶、GPx、TNF-α被主要考虑用于评估协同作用%。然而,酶ALT、AST、ALKP和MDA也被分析以支持协同作用。
评估ALT、AST、ALKP的原因:长期误用酒精改变肝功能的标志酶,诸如血清天冬氨酸转氨酶和丙氨酸转氨酶(AST、ALT)、碱性磷酸酶(ALKP),并且所以研究这些酶。
ALT和AST在肝细胞中被发现,但是AST在骨骼和心肌细胞中也被发现。在酒精相关的肝损伤中,AST比ALT升高得更多,至少部分作为酒精相关骨骼损伤的反映。在ALT超过AST的急性肝细胞疾病(例如,急性病毒性肝炎)中,这是正常模式的逆转。
ALKP是内衬肝的胆管的细胞中的酶。血浆中的ALKP水平将随着与改变的胆汁产生和/或分泌相关的肝病以及慢性肝病几乎伴随地升高。
评估氧化应激标志物(MDA、抗氧化剂酶[SOD、CAT、谷胱甘肽过氧 化物酶等]、还原的谷胱甘肽GSH])的原因:在肝中酒精代谢导致活性氧(ROS)的形成。酒精也刺激细胞色素P450的活性,细胞色素P450有助于ROS产生。此外,酒精可以改变体内某些金属的水平,从而促进ROS产生。最后,酒精降低可以消除ROS的试剂的水平(即内源性抗氧化剂)。产生的细胞的状态,被称为氧化应激,可以导致细胞损伤。肝细胞中的ROS产生和氧化应激在酒精性肝病的形成中起重要作用。
MDA(丙二醛)是细胞膜脂质过氧化作用的最终产物。ROS降解(氧化性降解)细胞膜的多不饱和脂肪酸,导致细胞损伤。脂质过氧化作用的程度可以很好地与组织MDA含量相关联。
SOD(超氧化物歧化酶)催化超氧化物自由基分解成氧气和过氧化氢。肝细胞富含SOD,因为其是与大量物质的代谢相关的主要器官。
CAT(过氧化氢酶)催化过氧化氢(H2O2)转化成水和氧气。此酶在大部分真核细胞中位于过氧化物酶体。
GPx(谷胱甘肽过氧化物酶)在大部分的细胞的细胞质中是最丰富地可用的。其在GSH存在下中和过氧化氢(H2O2)。
(GSH-还原的谷胱甘肽,GSSG-氧化的谷胱甘肽)
GSH在需氧细胞中是最丰富的抗氧化剂。GSH对于保护细胞免受氧化应激、用作自由基清除剂和脂质过氧化作用的抑制剂是关键的。GSH也参与由谷胱甘肽过氧化物酶(GPx)降解H2O2。还原的谷胱甘肽(GSH)与氧化的谷胱甘肽(GSSG)的比率是细胞健康(细胞氧化还原电势的状态)的指标。在正常健康条件下,GSH构成接近90%的细胞谷胱甘肽(即,GSH/GSSG是约9)。然而,在ROS相关紊乱中,GSH/GSSG比率被降低。
评估肿瘤坏死因子α(TNF-α)的原因:酒精消耗提高内毒素从肠道至门脉循环的转运并且与枯否细胞(免疫细胞)相互作用,导致包括肿瘤坏死因子α(TNF-α)的若干促炎症细胞因子的分泌。
基于以上描述,我们鉴定了某些关键标志物并且证明了选择的参数的重要性:
SOD、过氧化氢酶和GPx:在系统中,SOD催化超氧化物歧化为H2O2。然后,GPx和过氧化氢酶独立地将此H2O2转化成水。SOD与GPx和过氧化氢酶一起形成防御抵抗ROS的有害作用的主要酶。
GSH是保护细胞免受包括酒精的外源性物质的主要内源性抗氧化剂。酒精被认为在中和氧化剂的过程中消耗GSH水平。除此之外,内源性谷胱甘肽-谷胱甘肽过氧化物酶系统用作重要的抗氧化剂以及在暴露于乙醇的肝细胞中的细胞保护性机制。因此,细胞GSH水平的消耗在乙醇介导的肝细胞功能紊乱中起重要作用。
以下的表(1至9)例证单独成分、成分的组合的肝保护作用%以及使用各自组合呈现的协同作用%。所有动物实验通过每口服施用2.5g/kg剂量的酒精被进行持续一个月的时间段。
表1:D-甘露醇的保护作用%
表2:D-木糖醇&D-赤藓糖醇的保护作用%
表3:18β-甘草酸和18α-甘草酸的比较保护作用%
表6:18β-甘草酸-甘露醇、木糖醇&赤藓糖醇的比较保护作用%和协同作
用%
表7:(18β-甘草酸/甘露醇、木糖醇和赤藓糖醇)的保护作用%和协同
作用%的比较数据
表8:蔗糖、甘露糖、木糖&乳糖的保护作用%
在以上的表中提供的数据清楚地表明18β-GA/D-甘露醇组合呈现超过18β-GA/D-赤藓糖醇和18β-GA/D-木糖醇组合的优越的协同作用级别。
在以上的表中提供的数据还指示总体的18β-GA/D-甘露醇组合呈现与18α-GA/D-甘露醇组合几乎相似的协同作用级别。
还可以推断出18β-GA/还原性或非还原性单糖或二糖已经呈现较低程度的协同效应。
本发明被以下实施例例证。然而,应该理解的是本发明的范围不被实施例以任何方式限制。本领域技术人员将理解,本研究包括以下实施例并且还可以在本发明的范围内被修改并且改变。
材料和方法
试剂
蒸馏乙醇从BengalChemicals,WestBengal,India获得。生化试剂盒,像AST、ALT、ALKP以及总蛋白从SpanDiagnosticsLtd.Surat,India获得。[TimecoursestudyofoxidativeandnitrosativestressandantioxidantenzymesinK2Cr2O7-inducednephrotoxicity(K2Cr2O7诱导的肾毒性中的氧化和氮化应激以及抗氧化剂酶的时间进程研究).BMCNephrol.,6:4]。通过如在大鼠TNF-αELISA试剂盒(BioLegend,Inc.SanDiego,CA,USA)中提及的标准程序评估TNF-α。
在本研究中使用的所有化学品是分析级别的并且从以下公司获得:Sigma(St.Louis,MO,USA)、Merck(Mumbai,India)、S.D.FineChemicals(Mumbai,India)和Qualigen(Mumbai,India)。
大鼠中酒精诱导的亚急性肝毒性
称重为150-200g的雄性威斯塔白化大鼠(MaleWistaralbinorat)采购自本地注册交易商(CPCSEA注册号1443/po/6/4/CPCSEA),Kolkata,India并且在标准居住条件下被适应持续7天(26℃±2℃,60-70%RH,及12±1小时光和暗循环)。在实验时期期间动物用可商购的饮食(UptonIndiaPvt.Ltd,India)和水随意地喂养。
实施例
实施例1:
a)用于生物测试的模型:
称重为150-200g的雄性威斯塔白化大鼠被采购并且被随机分成每个组由六个动物组成的组。通过口服施用25%酒精(2.5gm/kg/天,口服)持续28天,在大鼠中通过酒精诱导亚急性毒性并且将此组用作阴性对照并且阳性对照组仅接受蒸馏水。
b)药物溶液的制备:
所有药物溶液在15-40%含水酒精中制备,将pH调整在4.0-9.0范围内,用于评估肝保护活性。将此溶液用蒸馏水进一步稀释以获得25%酒精水溶液并且通过强饲法口服施用至步骤(a)的不同大鼠组。
c)肝保护活性的评估:
在第28天,将动物用乙醚麻醉并且通过心脏穿刺收集血液样品并且血清被用于测定标志酶,也就是,血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)。在收集血液之后立即通过暴露于过剂量的乙醚将大鼠处死;将其肝移除,在冷盐水中洗涤。肝的一部分被用于制备在磷酸缓冲液(pH7.4)中的肝匀浆。将上清液用于评估丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原的谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GPx)。
实施例2:
将D-甘露醇(0.5g)溶解在含水酒精(100ml)中以提供0.5%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。将该施用实施超过28天的时间段;每天将10ml样品用6ml蒸馏水稀释以制备25%酒精水溶液(16ml)并且口服地喂养(10ml/kg/天)。按照实施例(1c)实施肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 12.26% |
SOD、CAT和GPx | 12.71% |
GSH | 10.35% |
肝MDA | 19.17% |
TNF-α | 7.19% |
实施例3:
将D-甘露醇(2.5g)溶解在含水酒精(100ml)中以提供2.5%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 29.71% |
SOD、CAT和GPx | 35.83% |
GSH | 31.53% |
肝MDA | 50.80% |
TNF-α | 31.46% |
实施例4:
将18β-甘草酸(0.1g)溶解在含水酒精(100ml)中以提供0.1%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 8.38% |
SOD、CAT和GPx | 11.45% |
GSH | 3.29% |
肝MDA | 15.97% |
TNF-α | 7.64% |
实施例5:
将D-甘露醇(2.5g)和18β-甘草酸(0.1g)溶解在含水酒精(100ml)中以提供2.6%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 40.35% |
SOD、CAT和GPx | 60.15% |
GSH | 48.24% |
肝MDA | 85.62% |
TNF-α | 50.56% |
实施例6:
将D-甘露醇(2.5g)和18β-甘草酸(1.0g)溶解在含水酒精(100ml)中以提供3.5%的溶液。将此溶液以若干部分施用至实施例1(a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 52.35% |
SOD、CAT和GPx | 78.75% |
GSH | 83.29% |
肝MDA | 93.29% |
TNF-α | 87.64% |
实施例7:
将D-甘露醇(0.5g)和18β-甘草酸(0.1g)溶解在含水酒精(100ml)中以提供0.6%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 21.0% |
SOD、CAT和GPx | 25.34% |
GSH | 17.64% |
肝MDA | 39.63% |
TNF-α | 19.16% |
实施例8:
将D-甘露醇(3.0g)和18β-甘草酸(0.1g)溶解在含水酒精(100ml)中以提供3.1%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 37.23% |
SOD、CAT和GPx | 58.15% |
GSH | 45.53% |
肝MDA | 70.87% |
TNF-α | 47.20% |
实施例9:
将D-甘露醇(2.5g)和18β-甘草酸(0.4g)溶解在含水酒精(100ml)中以提供2.9%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 53.15% |
SOD、CAT和GPx | 79.83% |
GSH | 76.38% |
肝MDA | 80.41% |
TNF-α | 81.62% |
实施例10:
将D-甘露醇/D-木糖醇/D-赤藓糖醇(1.0g)和18β-甘草酸(0.1g)溶解在含水酒精(100ml)中以提供1.1%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
实施例11:
将D-甘露醇/D-木糖醇/D-赤藓糖醇(2.5g)和18β-甘草酸(0.3g)溶解在含水酒精(100ml)中以提供2.8%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
实施例12:
将D-甘露糖/D-木糖/D-乳糖/D-蔗糖(2.5g)和18β-甘草酸(0.3g)溶解在含水酒精(100ml)中以提供2.8%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
实施例13:
将D-甘露糖/D-木糖/D-乳糖/D-蔗糖(1.0g)和18β-甘草酸(0.1g)溶解在含水酒精(100ml)中以提供1.1%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
实施例14:
将D-甘露醇(1.0g)和18α-甘草酸(0.1g)溶解在含水酒精(100ml)中以提供1.1%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 30.97% |
SOD、CAT和GPx | 42.42% |
GSH | 32.74% |
肝MDA | 54.16% |
TNF-α | 34.05% |
实施例15:
将D-甘露醇(2.5g)和18α-甘草酸(0.3g)溶解在含水酒精(100ml)中以提供2.8%的溶液。将此溶液以若干部分施用至实施例(1a)的大鼠组中的一组。如在实施例2中提及以及按照实施例(1c)实施施用、样品稀释、口服喂养和肝保护活性的评估。
平均肝保护作用%:
ALT、AST和ALKP | 46.49% |
SOD、CAT和GPx | 69.06% |
GSH | 57.44% |
肝MDA | 75.80% |
TNF-α | 68.1% |
实施例16:
制备方法:
将0.1至0.4克的18β/α-甘草酸溶解在15-40%酒精或酒精:水混合物(以100ml)中。将糖醇或糖(0.5克至3.0克)添加至此溶液中。将获得的溶液充分混合以获得澄清溶液。此后,将获得的溶液的pH调整至4.0-9.0之间并且任选地添加期望的调味剂(香草)以获得最终的酒精饮料组合物。
在本申请中使用的缩写的扩展被枚举如下:
GA:甘草酸(Glycyrrhizin)(甘草酸(Glycyrrhizicacid)或甘草酸(Glycyrrhizinicacid)或18β-甘草酸)
Man:甘露醇
Xyl:木糖醇
Ery:赤藓糖醇
Mans:甘露糖
Suc:蔗糖
Xyls:木糖
Lac:乳糖
SOD等:SOD、CAT&GPx
ALT等:ALT、AST和ALKP
Mat:苦参碱
本发明的优点:
1.本发明的酒精饮料具有较好的肝保护作用。
2.本发明的酒精饮料具有可接受的气味、味道、澄清度和可接受的陶醉感因素。
Claims (12)
1.一种酒精饮料组合物,提供协同肝保护,所述酒精饮料组合物包含:
a)肝保护剂,
b)酒精或水或其混合物,
c)pH调整剂,及
d)任选地调味剂。
2.如权利要求1所述的饮料组合物,其中所述肝保护剂选自由18β-甘草酸、18α-甘草酸、糖醇和糖组成的组。
3.如权利要求2所述的饮料组合物,其中所述糖醇选自由D-甘露醇、D-木糖醇、D-赤藓糖醇组成的组,并且所述糖选自由D-蔗糖、D-甘露糖、D-木糖和D-乳糖组成的组。
4.如前述权利要求中任一项所述的饮料组合物,其中所述肝保护剂是选自由18β-甘草酸、18α-甘草酸、以及D-甘露醇、D-木糖醇、D-赤藓糖醇、D-蔗糖、D-甘露糖、D-木糖和D-乳糖中的任一种或其混合物组成的组的组合。
5.如权利要求4所述的饮料组合物,其中18β-甘草酸是在0.05%至0.4%,优选地0.1%至0.3%的范围内,并且D-甘露醇、D-木糖醇、D-赤藓糖醇、D-木糖、D-甘露糖、D-蔗糖、D-乳糖或其混合物是在0.5%至3.0%,优选地1.0%至2.5%的范围内;并且其中18α-甘草酸是在0.05%至0.3%,优选地0.1%至0.3%的范围内,并且D-甘露醇、D-木糖醇、D-赤藓糖醇或其混合物是在0.5%至3.0%,优选地1.0%至2.5%的范围内。
6.如前述权利要求中任一项所述的饮料组合物,其中较优选的肝保护剂是18β/18α-甘草酸和D-甘露醇的组合。
7.如权利要求6所述的饮料组合物,其中18β-甘草酸是在0.05%至0.4%的范围内并且所述D-甘露醇是在0.5%至3.0%的范围内,并且优选地18β-甘草酸在0.1%至0.3%的范围内并且所述D-甘露醇是在1.0%至2.5%的范围内;并且其中18α-甘草酸是在0.1%至0.3%的范围内并且所述D-甘露醇是在1.0%至2.5%的范围内。
8.如权利要求1所述的饮料组合物,其中pH调整剂是有机或无机碱/缓冲液,优选地选自山梨酸钾或磷酸钠(单碱式或二碱式或三碱式)。
9.如权利要求1所述的饮料组合物,其中所述调味剂选自香草香料、草莓香料。
10.一种用于制备权利要求1所述的酒精饮料组合物的工艺,包括以下步骤:(a)获得酒精或水或其混合物,(b)使18β-甘草酸或18α-甘草酸与步骤(a)中的所述酒精或水或酒精和水的混合物混合,(c)将糖醇或糖添加至步骤(b)中的混合物,(d)将步骤(c)中所获得的溶液的pH调整在4.0-9.0之间,(e)任选地添加调味剂及(f)获得所要求的酒精饮料组合物。
11.如权利要求1所述的酒精饮料组合物用于提供降低的肝毒性的用途。
12.如权利要求1的酒精饮料,用于在缓解涉及急性和慢性毒性的疾病诸如像由酒精诱导的毒性引起的脂肪变性、脂肪性肝炎、纤维化、肝硬化及肝细胞癌等的酒精性肝病(ALD)的方法中使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1894/CHE/2013 | 2013-04-29 | ||
IN1894CH2013 IN2013CH01894A (zh) | 2013-04-29 | 2014-04-28 | |
PCT/IB2014/061051 WO2014177989A2 (en) | 2013-04-29 | 2014-04-28 | Reduced toxicity in alcoholic beverages |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105143428A true CN105143428A (zh) | 2015-12-09 |
CN105143428B CN105143428B (zh) | 2017-08-25 |
Family
ID=50981589
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201480023673.7A Active CN105143428B (zh) | 2013-04-29 | 2014-04-28 | 酒精饮料中降低的毒性 |
Country Status (12)
Country | Link |
---|---|
US (2) | US9149491B2 (zh) |
EP (1) | EP2992078B1 (zh) |
JP (1) | JP6194412B2 (zh) |
CN (1) | CN105143428B (zh) |
AU (1) | AU2014261082B2 (zh) |
BR (1) | BR112015026884A2 (zh) |
CA (1) | CA2909855C (zh) |
EA (1) | EA030485B1 (zh) |
ES (1) | ES2743075T3 (zh) |
IN (1) | IN2013CH01894A (zh) |
MX (1) | MX2015014956A (zh) |
WO (1) | WO2014177989A2 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2017016479A (es) | 2015-06-19 | 2018-08-15 | Chigurupati Harsha | Composicion de bebidas sinergicas. |
AU2016327930B2 (en) * | 2015-09-24 | 2021-04-15 | Sinew Pharma Inc. | Compounds effective in treating hepatotoxicity and fatty liver diseases and uses thereof |
WO2017084234A1 (zh) * | 2015-11-19 | 2017-05-26 | 欣耀生医股份有限公司 | 预防或治疗脂肪肝的药物组合物 |
EP3257513A1 (en) * | 2016-06-18 | 2017-12-20 | Chigurupati, Harsha | Composition to reduce dna and hepatic damage and to enhance repair thereof |
WO2018061020A1 (en) * | 2016-09-30 | 2018-04-05 | Chigurupati Harsha | A composition for dna protection |
CN108753551A (zh) * | 2018-07-05 | 2018-11-06 | 深圳市鑫木森实业发展有限公司 | 一种具有补肾养肝功效的sod白酒制备方法 |
WO2021050263A1 (en) * | 2019-09-12 | 2021-03-18 | Coors Brewing Company | METHOD AND SYSTEM OF BEER SHELF LIFE EXTENSION BY pH NEUTRALIZATION |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1448497A (zh) * | 2002-03-28 | 2003-10-15 | 庄玉坤 | 减轻肝损伤或者不损伤肝脏的酒类饮料 |
Family Cites Families (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1720329A (en) | 1926-09-25 | 1929-07-09 | Us Process Corp | Manufacture of fermented beverages of reduced alcohol content |
US3107605A (en) * | 1960-09-23 | 1963-10-22 | Colonial Sugar Refining Co | Extracting sucrose from sugar cane |
US3282706A (en) | 1964-11-23 | 1966-11-01 | Macandrews & Forbes Company | Sucrose-ammoniated glycyrrhizin sweetening agent |
US4393200A (en) | 1980-01-09 | 1983-07-12 | Maruzen Kasei Kabushiki Kaisha | 18 α-Glycyrrhizinic acid and salt thereof |
JPS58870A (ja) | 1981-06-20 | 1983-01-06 | Hayashibara Biochem Lab Inc | 飲食物及びその製造方法 |
EP0502554A3 (en) | 1986-05-15 | 1993-03-10 | Emory University | Composition comprising an oxygen radical scavenger and a surfaceactive copolymer |
US4898890A (en) | 1986-06-21 | 1990-02-06 | Dainippon Ink And Chemicals, Inc. | Medicines for use in the therapy and prevention of kidney and liver diseases |
EP0336960A4 (en) | 1987-10-19 | 1990-02-20 | Joseph A Haklitch | DETOXIDATION ADDITIVES FOR FOODSTUFFS. |
US4868207A (en) | 1988-07-28 | 1989-09-19 | Taisho Pharmaceutical Co., Ltd. | Bis (methylenedioxy) biphenyl compounds useful for the treatment of liver diseases |
JP2815402B2 (ja) * | 1989-06-12 | 1998-10-27 | タマ生化学株式会社 | グリチルリチン製剤 |
KR0177832B1 (ko) * | 1990-07-18 | 1999-02-01 | 미끼 도꾸따로오 | 감초 추출물을 사용한 조성물 |
JP3090980B2 (ja) | 1991-07-05 | 2000-09-25 | 勲 北川 | 肝細胞増殖促進剤および肝障害防止剤 |
JPH0614746A (ja) | 1992-06-29 | 1994-01-25 | Oomiya Yakugyo Kk | 健康飲料 |
JPH06192107A (ja) * | 1992-12-25 | 1994-07-12 | Sanwa Kagaku Kenkyusho Co Ltd | グリチルリチン経口剤 |
US6099844A (en) * | 1994-08-22 | 2000-08-08 | Triarco Industries, Inc. | Increasing yield of extractable substances from botanicals with an enzyme composition |
JPH09143085A (ja) | 1995-11-17 | 1997-06-03 | Eisai Co Ltd | 甘草成分含有強肝剤 |
US6855526B2 (en) * | 2002-05-15 | 2005-02-15 | The United States Of America As Represented By The Secretary Of Agriculture | Method for making mannitol with Lactobacillus intermedius |
FI20021819A0 (fi) | 2002-10-14 | 2002-10-14 | Pekka Untamo Heino | Valmiste alkoholin metabolian tehostamiseksi |
JP4601936B2 (ja) | 2002-10-29 | 2010-12-22 | 株式会社ミノファーゲン製薬 | Mcp−1産生抑制のための薬学的組成物 |
EP1875816A3 (en) * | 2003-07-10 | 2008-03-12 | Carl A. Forest | Beverages with specialized supplements |
CN1835758A (zh) | 2003-08-12 | 2006-09-20 | 日本脏器制药株式会社 | 高浓度甘草甜素制剂 |
KR100543257B1 (ko) | 2003-10-02 | 2006-01-20 | 재단법인서울대학교산학협력재단 | 감초 추출물 또는 리퀴리티게닌을 포함하는 중금속중독으로 인한 질환의 치료 및 예방용 조성물 |
CN100539877C (zh) * | 2005-07-05 | 2009-09-16 | 黄恒燊 | 解酒保肝饮料及其制备方法 |
KR100697056B1 (ko) * | 2006-01-09 | 2007-03-20 | 재단법인서울대학교산학협력재단 | 리퀴리티게닌을 유효성분으로 포함하는 간질환의 예방 및치료용 조성물 |
CN100455215C (zh) * | 2006-06-05 | 2009-01-28 | 谢春生 | 一种具有解酒功能的梨汁饮料及其制备方法 |
EP2089505A4 (en) | 2006-11-08 | 2010-01-06 | Morning After Herbal Infusion | ALCOHOLIC BEVERAGE WITH REDUCED EYE SENSATION |
KR20080002772U (ko) * | 2007-01-17 | 2008-07-22 | 방기덕 | 저고온 액화 포도주 |
US20080226787A1 (en) | 2007-03-14 | 2008-09-18 | Concentrate Manufacturing Company Of Ireland | Ammoniated Glycyrrhizin Modified Sweetened Beverage Products |
EP2151451A4 (en) * | 2007-03-23 | 2010-06-02 | Nisshin Pharma Inc | COMPOSITION FOR PREVENTING OR TREATING PULMONARY DISEASE |
JP2008266203A (ja) | 2007-04-19 | 2008-11-06 | Bussan Food Science Kk | 活性酸素種消去酵素群の活性を向上させる方法 |
US20090162483A1 (en) * | 2007-12-20 | 2009-06-25 | Wendy Lynn Constantine | Sports beverage and method of making |
CN101473985A (zh) * | 2007-12-31 | 2009-07-08 | 天津中新药业研究中心 | 一种含有中药提取物和氨基酸成分饮料的制备方法 |
US20100086666A1 (en) | 2008-10-03 | 2010-04-08 | Andrew Adelman | Alcoholic beverage |
CN101744865B (zh) * | 2008-12-18 | 2012-07-25 | 山东福田药业有限公司 | 一种木糖醇护肝片的制备方法 |
US20090196951A1 (en) | 2009-03-16 | 2009-08-06 | Ross Brandborg | Product and Method for Alcoholic Beverage Infused with Resveratrol |
IT1399791B1 (it) | 2009-04-20 | 2013-05-03 | Drugs Minerals And Generics Italia S R L In Forma Abbreviata D M G Italia S R L | Composizioni farmaceutiche per il trattamento della poliposi nasale |
US8524785B2 (en) | 2009-09-04 | 2013-09-03 | International Flavors And Fragrances Inc. | Methods for using rebaudioside C as a flavor enhancer |
CN101946947A (zh) * | 2010-09-01 | 2011-01-19 | 佛山市昌荣农业科技有限公司 | 一种灵芝葛根汁 |
CN102450712A (zh) | 2010-10-22 | 2012-05-16 | 赵强 | 一种玉米须营养液 |
CN102450714A (zh) * | 2010-10-22 | 2012-05-16 | 赵强 | 一种解酒饮料及其制备方法 |
CN102660445A (zh) * | 2012-06-06 | 2012-09-12 | 重庆修贤商贸有限公司 | 功能性低损伤养生酒 |
-
2014
- 2014-04-28 WO PCT/IB2014/061051 patent/WO2014177989A2/en active Application Filing
- 2014-04-28 IN IN1894CH2013 patent/IN2013CH01894A/en unknown
- 2014-04-28 CA CA2909855A patent/CA2909855C/en active Active
- 2014-04-28 ES ES14732377T patent/ES2743075T3/es active Active
- 2014-04-28 BR BR112015026884A patent/BR112015026884A2/pt not_active Application Discontinuation
- 2014-04-28 JP JP2016511153A patent/JP6194412B2/ja active Active
- 2014-04-28 CN CN201480023673.7A patent/CN105143428B/zh active Active
- 2014-04-28 EA EA201592077A patent/EA030485B1/ru not_active IP Right Cessation
- 2014-04-28 US US14/376,039 patent/US9149491B2/en active Active
- 2014-04-28 EP EP14732377.8A patent/EP2992078B1/en active Active
- 2014-04-28 AU AU2014261082A patent/AU2014261082B2/en active Active
- 2014-04-28 MX MX2015014956A patent/MX2015014956A/es unknown
-
2015
- 2015-09-14 US US14/852,794 patent/US10039776B2/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1448497A (zh) * | 2002-03-28 | 2003-10-15 | 庄玉坤 | 减轻肝损伤或者不损伤肝脏的酒类饮料 |
Non-Patent Citations (4)
Title |
---|
何东等: "D-木糖对酒精致肝细胞脂肪性变的保护作用", 《世界华人消化杂志》 * |
复方甘草酸苷联合木糖醇治疗非酒精性脂肪肝合并糖尿病的疗效观察 ;赵静等;《现代医药卫生》;20061015(第19期);第2951-2952页 * |
复方甘草酸苷联合木糖醇治疗非酒精性脂肪肝合并糖尿病的疗效观察 ;赵静等;《现代医药卫生》;20061015(第19期);第2951页摘要,第2952页右栏 * |
赵静等: "复方甘草酸苷联合木糖醇治疗非酒精性脂肪肝合并糖尿病的疗效观察", 《现代医药卫生》 * |
Also Published As
Publication number | Publication date |
---|---|
EP2992078B1 (en) | 2019-06-12 |
EP2992078A2 (en) | 2016-03-09 |
ES2743075T3 (es) | 2020-02-18 |
CA2909855A1 (en) | 2014-11-06 |
US9149491B2 (en) | 2015-10-06 |
JP2016516442A (ja) | 2016-06-09 |
CN105143428B (zh) | 2017-08-25 |
WO2014177989A3 (en) | 2015-03-05 |
EA201592077A1 (ru) | 2016-05-31 |
CA2909855C (en) | 2016-08-30 |
US20170071963A1 (en) | 2017-03-16 |
WO2014177989A2 (en) | 2014-11-06 |
MX2015014956A (es) | 2016-08-08 |
IN2013CH01894A (zh) | 2015-10-02 |
AU2014261082A1 (en) | 2015-12-17 |
JP6194412B2 (ja) | 2017-09-06 |
EA030485B1 (ru) | 2018-08-31 |
US20150141358A1 (en) | 2015-05-21 |
AU2014261082B2 (en) | 2016-06-16 |
BR112015026884A2 (pt) | 2017-07-25 |
US10039776B2 (en) | 2018-08-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105143428A (zh) | 酒精饮料中降低的毒性 | |
Bagul et al. | Application of resveratrol in diabetes: rationale, strategies and challenges | |
KR101281988B1 (ko) | 가시오가피를 함유한 숙취 해소 및 간기능 개선용 생약조성물 및 그 제조방법 | |
KR20140090453A (ko) | 아로니아 추출물을 함유하는 숙취예방, 숙취해소 또는 간 보호용 조성물 | |
JP5545692B2 (ja) | キサンチンオキシダーゼ阻害剤及び血漿中尿酸値低下剤 | |
KR101371143B1 (ko) | 클로렐라를 유효성분으로 포함하는 간기능 개선 또는 숙취해소용 조성물 | |
JPH11246398A (ja) | 生体内過酸化脂質増加に起因する疾患の予防または治療剤 | |
CN104244937A (zh) | 含ramalin的用于预防或治疗肝纤维化和肝硬化的药物组合物 | |
KR101819026B1 (ko) | 제주도 자생식물 발효물을 유효성분으로 함유하는 알코올성 위 손상 억제, 알코올 흡수 억제 또는 숙취 해소용 조성물 | |
KR20140137289A (ko) | 포공영 추출물을 함유하는 숙취해소 및 간 질환의 치료 및 예방용 조성물 | |
JP4777495B2 (ja) | アルコール障害予防剤およびそれを含有する食品 | |
JP4974553B2 (ja) | アセトアルデヒド代謝促進剤 | |
KR20140137288A (ko) | 고량강 추출물을 함유하는 숙취해소 및 간 질환의 치료 및 예방용 조성물 | |
KR100631073B1 (ko) | 더덕 추출물을 포함하는 알코올성 간 질환 및 알코올성고지혈증의 예방 및 치료용 조성물 | |
KR101692604B1 (ko) | 저속으로 추출한 석류주스를 유효성분으로 포함하는 간 기능 개선용 조성물 | |
WO2005027656A1 (ja) | 機能性甘味料 | |
KR20190138114A (ko) | 흑무 발효물을 유효성분으로 포함하는 간 질환 예방, 개선 또는 치료용 조성물 | |
KR20140026737A (ko) | 발효울금 분말을 함유한 알코올성 간손상 보호용 조성물 | |
US20240123019A1 (en) | Composition for treating or ameliorating liver disease and liver dysfunction comprising zizania latifolia extract | |
KR20220107669A (ko) | 벌나무 추출물 및 버섯 추출물의 혼합물을 유효성분으로 포함하는 비알코올성 지방간의 예방, 개선 또는 치료용 약학적 조성물 및 이의 제조방법 | |
KR20090018524A (ko) | 민들레 추출물을 포함하는 알코올성 간질환의 예방 및치료용 조성물 | |
US10046017B2 (en) | Pomegranate skin extract for treating fatty liver | |
KR20230122822A (ko) | 천마 추출물을 유효성분으로 포함하는 항비만 조성물 | |
KR20240088908A (ko) | Ampk 활성화제, 운동 기능 향상제, 근지구력 향상제 및 근위축 억제제 | |
Kim et al. | Akebia quinata Extract Combined with Korean Traditional Juice Activates Antioxidant Enzymes and Reduces Apoptosis and Inflammation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20160907 Address after: Hyderabad Applicant after: Harsha Chigurupati Address before: Andhra Pradesh Applicant before: CHIGURUPATI TECHNOLOGIES PRIVATE LTD |
|
GR01 | Patent grant | ||
GR01 | Patent grant |