CN109985206A - 用于防治酒精性肝损伤的组合物 - Google Patents
用于防治酒精性肝损伤的组合物 Download PDFInfo
- Publication number
- CN109985206A CN109985206A CN201811165485.4A CN201811165485A CN109985206A CN 109985206 A CN109985206 A CN 109985206A CN 201811165485 A CN201811165485 A CN 201811165485A CN 109985206 A CN109985206 A CN 109985206A
- Authority
- CN
- China
- Prior art keywords
- weight
- drug
- composition
- liver
- parts
- 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.)
- Pending
Links
- 231100000753 hepatic injury Toxicity 0.000 title claims abstract description 43
- 230000001476 alcoholic effect Effects 0.000 title claims abstract description 42
- 206010067125 Liver injury Diseases 0.000 title claims abstract description 41
- 239000000203 mixture Substances 0.000 title claims abstract description 29
- 244000163122 Curcuma domestica Species 0.000 claims abstract description 11
- 235000003392 Curcuma domestica Nutrition 0.000 claims abstract description 11
- 240000008669 Hedera helix Species 0.000 claims abstract description 11
- 244000202052 Poncirus trifoliata Species 0.000 claims abstract description 11
- 235000000404 Poncirus trifoliata Nutrition 0.000 claims abstract description 11
- 235000003373 curcuma longa Nutrition 0.000 claims abstract description 11
- 235000013976 turmeric Nutrition 0.000 claims abstract description 11
- 244000046146 Pueraria lobata Species 0.000 claims abstract description 9
- 235000010575 Pueraria lobata Nutrition 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims description 50
- 229940079593 drug Drugs 0.000 claims description 39
- 210000002966 serum Anatomy 0.000 claims description 15
- 102000002260 Alkaline Phosphatase Human genes 0.000 claims description 8
- 108020004774 Alkaline Phosphatase Proteins 0.000 claims description 8
- 238000008050 Total Bilirubin Reagent Methods 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 102000009027 Albumins Human genes 0.000 claims description 7
- 108010088751 Albumins Proteins 0.000 claims description 7
- 235000013402 health food Nutrition 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 108090000623 proteins and genes Proteins 0.000 claims description 6
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 claims description 4
- 108010082126 Alanine transaminase Proteins 0.000 claims description 4
- 235000013361 beverage Nutrition 0.000 claims description 4
- 244000062793 Sorghum vulgare Species 0.000 claims description 3
- 235000019713 millet Nutrition 0.000 claims description 3
- -1 oral solution Substances 0.000 claims description 3
- 239000010902 straw Substances 0.000 claims description 3
- 239000003292 glue Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229940100688 oral solution Drugs 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 238000012377 drug delivery Methods 0.000 claims 1
- 239000008187 granular material Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 235000019441 ethanol Nutrition 0.000 description 33
- 210000004185 liver Anatomy 0.000 description 22
- 210000001519 tissue Anatomy 0.000 description 14
- 241000700159 Rattus Species 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 230000002440 hepatic effect Effects 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 238000004043 dyeing Methods 0.000 description 9
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical group CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000835 fiber Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 208000019425 cirrhosis of liver Diseases 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 229960004756 ethanol Drugs 0.000 description 6
- 230000002496 gastric effect Effects 0.000 description 6
- 230000008595 infiltration Effects 0.000 description 6
- 238000001764 infiltration Methods 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 206010016654 Fibrosis Diseases 0.000 description 5
- 244000020551 Helianthus annuus Species 0.000 description 5
- 235000003222 Helianthus annuus Nutrition 0.000 description 5
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 208000002353 alcoholic hepatitis Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003246 corticosteroid Substances 0.000 description 5
- 239000000975 dye Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 208000010706 fatty liver disease Diseases 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 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 4
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000011049 filling Methods 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
- 206010020718 hyperplasia Diseases 0.000 description 4
- 210000005229 liver cell Anatomy 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 231100000240 steatosis hepatitis Toxicity 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 3
- 208000007082 Alcoholic Fatty Liver Diseases 0.000 description 3
- 206010016262 Fatty liver alcoholic Diseases 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 3
- 108090000340 Transaminases Proteins 0.000 description 3
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 229940096397 interleukin-8 Drugs 0.000 description 3
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 210000005228 liver tissue Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 229960001476 pentoxifylline Drugs 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 238000009168 stem cell therapy Methods 0.000 description 3
- 238000009580 stem-cell therapy Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 102000014898 transaminase activity proteins Human genes 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- RYKKQQUKJJGFMN-HVDRVSQOSA-N 4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol;(2s)-5-oxopyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC(=O)N1.CC1=NC=C(CO)C(CO)=C1O RYKKQQUKJJGFMN-HVDRVSQOSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- 208000004930 Fatty Liver Diseases 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 206010061998 Hepatic lesion Diseases 0.000 description 2
- 206010019708 Hepatic steatosis Diseases 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 2
- KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 206010046274 Upper gastrointestinal haemorrhage Diseases 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000004596 appetite loss Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000009223 counseling Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 238000007905 drug manufacturing Methods 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000019017 loss of appetite Diseases 0.000 description 2
- 235000021266 loss of appetite Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 229960002662 propylthiouracil Drugs 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000001671 psychotherapy Methods 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000007863 steatosis Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 208000016261 weight loss Diseases 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 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 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- 101710142885 Arginine N-succinyltransferase Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010017964 Gastrointestinal infection Diseases 0.000 description 1
- 206010018276 Gingival bleeding Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 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
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 206010019842 Hepatomegaly Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 102100023105 Sialin Human genes 0.000 description 1
- 101710105284 Sialin Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 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 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- GCNLQHANGFOQKY-UHFFFAOYSA-N [C+4].[O-2].[O-2].[Ti+4] Chemical compound [C+4].[O-2].[O-2].[Ti+4] GCNLQHANGFOQKY-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- RZUBARUFLYGOGC-MTHOTQAESA-L acid fuchsin Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=C(N)C(C)=CC(C(=C\2C=C(C(=[NH2+])C=C/2)S([O-])(=O)=O)\C=2C=C(C(N)=CC=2)S([O-])(=O)=O)=C1 RZUBARUFLYGOGC-MTHOTQAESA-L 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 108010081577 aldehyde dehydrogenase (NAD(P)+) Proteins 0.000 description 1
- 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 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 210000000026 apposition eye Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 208000019836 digestive system infectious disease Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 230000003082 hepatotoxic effect Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 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
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- JMZOMFYRADAWOG-UHFFFAOYSA-N methyl 7-methoxy-4-(7-methoxy-5-methoxycarbonyl-1,3-benzodioxol-4-yl)-1,3-benzodioxole-5-carboxylate Chemical group COC(=O)C1=CC(OC)=C2OCOC2=C1C1=C2OCOC2=C(OC)C=C1C(=O)OC JMZOMFYRADAWOG-UHFFFAOYSA-N 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 108010033145 microsomal ethanol-oxidizing system Proteins 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000000879 optical micrograph Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000004783 oxidative metabolism Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000003617 peroxidasic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/488—Pueraria (kudzu)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及用于防治酒精性肝损伤的组合物，所述组合物包括葛根花、白扁豆花、棋枳子、升麻、姜黄和葛根。
Description
技术领域
本发明涉及用于防治酒精性肝损伤的组合物，所述组合物包括葛根花、白扁豆花、椇枳子、升麻、姜黄和葛根。
背景技术
酒精性肝损伤是指过度饮酒导致的肝脏损伤，肝脏发生脂肪堆积、炎症以及瘢痕化，是不可忽视的临床疾病之一。近年来,酒精滥用和酒精依赖引起的疾病已成为当今世界日益严重的公共卫生问题。在非病毒性肝病中，酒精性肝损伤的发病率占据首位。在西方国家，酒精性脂肪肝是导致肝硬化的主要病因，也是十大常见致死病因之一。在我国，酒精性肝损伤的发病率也在日益增加，成为我国继病毒性肝炎后导致肝损害的第二大病因。
发病机制：酒精性肝损伤的发病机制还未完全明确。肝脏是人体中最复杂的器官之一，有超过500种功能，包括过滤血液毒素、储存能量、产生激素和蛋白质，以及调节胆固醇和血糖。酒精主要在十二指肠和上段回肠被吸收，仅2％～10％通过肺和肾脏排出，其余90％～98％在肝脏内代谢。酒精在肝脏中通过乙醇脱氢酶(Alcohol dehydrogenase,ADH)和微粒体乙醇氧化酶系统(microsome ethanol oxidation system,MEOS)进行氧化代谢，主要中间代谢产物为乙醛。乙醛进一步在乙醛脱氢酶的作用下生成乙酸，最终生成二氧化碳和水。酒精性肝损伤主要是乙醇及其衍生物乙醛代谢过程中直接或间接导致的，过量摄入酒精后，它们能够导致促炎细胞因子(例如TNF-α、白细胞介素6[IL-6]以及白细胞介素8[IL-8])的分泌，并使肝脏出现氧化应激、脂质过氧化反应和乙醛毒性，从而使肝脏出现炎症、细胞凋亡和肝细胞纤维化。此外，流行病学调查资料表明，酒精所致的肝损伤是有阈值效应的，即达到一定饮酒量或饮酒年限，就会大大增加肝损害风险，有证据显示，未成年及老人饮酒危害大；大量饮酒导致热量增加、食欲减少，使得维生素、脂肪、蛋白质和矿物质等营养物质缺乏，能够进一步加剧乙醇肝毒性。此外，女性对酒精介导肝毒性的敏感性是男性的两倍,并可能在较低剂量与更短饮酒时间下出现酒精性肝损伤。
临床诊断：酒精性肝损伤病型分类包括脂肪肝、酒精性肝炎、肝纤维化、肝硬化，甚至肝细胞癌。酒精性脂肪肝一般没有症状，有人可出现乏力、倦怠、食欲不振、腹胀、恶心、呕吐等表现，还会有肥胖、肝脏肿大等体征。酒精性肝炎患者发病前往往短期内曾大量饮洒，临床表现除了有酒精性脂肪肝的症状外，还有发热、腹痛、腹泻等，且有明显的体重减轻。患者可出现贫血和中性粘细胞增多、转氨酶升高、血清胆红素增高等表现。洒精性肝硬化患者早期无症状，中后期可出现体重减轻、食欲不振、腹痛、乏力、发热、尿色深、齿龈出血等症状。肝硬化失代偿则可出现黄疸、腹水、浮肿、上消化道出血等症状，实验室检查可有贫血、白细胞和血小板下降、血清白蛋白降低、球蛋白增高表现。
截至目前，酒精性肝损伤的治疗主要包括以下方法：
1.戒酒：对已发展至酒精性肝损伤的患者，最重要和有效的治疗措施是立即停止酒精的摄入。戒酒有利于提高酒精性肝损伤患者的生存率和预后，并可有效阻止患者向肝硬化或肝癌转化；
2.营养治疗：长期的酒精性肝损伤患者尤其是酒精性肝炎患者，往往伴有营养不良。而严重的营养不良又将使酒精性肝损伤临床指标进一步恶化。因此改善患者的营养状况有助于酒精性肝损伤的治疗。根据患者的体质，在采用药物等其他措施治疗过程中,每日应额外给予1.2～1.5g/kg蛋白、35～ 40kcal/kg热量以及适量的维生素A、维生素B、维生素D，叶酸及镁、硒和锌等离子；
3.药物治疗：①皮质类固醇：通过下调转录前炎症细胞因子TNF-α和 IL-8等减少炎症反应，是目前主要的治疗重度酒精性肝炎的药物，但其对早期酒精性肝损伤并无确切疗效。同时，皮质类固醇治疗酒精性肝损伤时可能诱发上消化道出血和感染等并发症；
②己酮可可碱：可作为皮质类固醇的替代药物，其主要机制为通过抑制磷酸二酯酶活性、上调细胞内cAMP，进而抑制炎症反应。但有研究发现，对皮质类固醇治疗无响应的患者对己酮可可碱的治疗同样不响应；
③抗TNF-α治疗：抗TNF-α药物可阻断TNF-α介导的炎症过程,进而可能缓解或阻止酒精性肝炎的发生发展。抗TNF-α药物可阻断TNF-α介导的炎症过程,进而可能缓解或阻止酒精性肝炎的发生发展；
④抗氧化剂：目前,临床常用的治疗酒精性肝损伤的抗氧化剂有N-乙酰半胱氨酸和美他多辛。巯醇化合物N-乙酰半胱氨酸是体内还原性谷胱甘肽前体,可增加谷胱甘肽的合成,增强谷胱甘肽-S-转移酶的活性,从而促进肝细胞解毒；美他多辛则和维生素B6、吡咯酮等联合用药,可显著改善酒精性肝损伤的生存率；
⑤其它药物：包括丙硫氧嘧啶、秋水仙素、多不饱和卵磷脂和血管收缩素Ⅱ受体阻断剂等；
4.中药治疗：近年来运用中药治疗酒精性肝损伤成为研究的一大热点，中药中的活性成分体现出了独特的作用，比如当归多糖可增强抗氧化酶SOD、 CAT、GSH-Px活性，提高机体抗氧化系统清除自由基的能力；白藜芦醇能清除氧自由基，减轻炎性反应，抗脂质过氧化损伤，对酒精所致小鼠肝损伤有一定的抑制作用；茶多酚能有效络合铁离子与低分子铁结合成配合物，促使低分子铁排出体外，从而减少自由基的形成。此外，小柴胡丹、丹参桃仁等,可通过解酒舒肝、促进血液循环等改善酒精性肝损伤的病理改变；
5.肝移植：对己酮可可碱和皮质类固醇等药物治疗不响应的严重的酒精性肝损伤患者，肝移植成为其延长生命最有效的治疗手段。目前，肝移植是唯一可能治愈重度酒精性肝损伤的方法，然而，肝脏供体的短缺严重制约了重度酒精性肝损伤的治疗；
6.干细胞治疗：近年来干细胞技术被应用于酒精性肝损伤的治疗。干细胞可以减少肝细胞的炎症反应从而改善纤维化,因此干细胞治疗是肝硬化患者的一个可能的治疗措施。干细胞治疗酒精性肝损伤的机制是注射入人体的间充质干细胞(mesenchymal stemcell,MSC)自动识别并迁移至细胞受损部位,增殖成新的肝细胞，促进受损和病变细胞进行自身修复,从而恢复细胞功能；
7.精神治疗：酒精性肝损伤患者要保持良好的心态,以免因心理压力和精神因素导致病情的加重,影响疾病的治疗效果。因此,酒精性肝损伤患者在戒酒和积极治疗的过程中,必要时可咨询心理学家进行精神治疗,社会也正在完善为酒精性肝损伤患者的戒酒和治疗提供必要的咨询服务。
综上所述，酒精性肝损伤是长期大量摄入酒精诱发肝脏的一系列病变的结果。从脂肪肝到肝炎，再到肝硬化和肝癌，其发生发展的机制仍有许多未知的环节。酒精性肝损伤的治疗，如药物疗法、营养疗法、肝移植等的发展也都较为缓慢。在解决酒精性肝损伤这个全球性的公共健康问题方面，依然有许多环节需要攻克。借助技术的发展进步和生命科学领域的深入探索，研发新型的安全高效病理生理主导的治疗方法，是治疗酒精性肝损伤的必然趋势。
发明内容
本发明提供了用于防治酒精性肝损伤的组合物，所述组合物包括葛根花、白扁豆花、椇枳子、升麻、姜黄和葛根。本发明的组合物具有以下功效：解毒降浊、清泻湿热，能够改善酒精所致肝损伤，降低血清转氨酶、胆红素、减轻肝脏病理损伤。并且，本发明的组合物为纯中药成分，毒性较低。
第一方面，本发明提供了组合物，所述组合物包括葛根花、白扁豆花、椇枳子、升麻、姜黄和葛根。
所述组合物以重量份计的配方如下:葛根花5-60重量份，白扁豆花5-30 重量份，椇枳子5-30重量份，升麻5-30重量份，姜黄5-60重量份。
优选地，所述组合物的配比如下：葛根花30g，白扁豆花30g，椇枳子 10g，升麻15g，姜黄15g，以及葛根15g。
优选地，所述组合物可制成保健食品及临床或药学上可接受的片剂、胶囊剂、颗粒剂、口服液、固体饮料、液体饮料的形式。
第二方面，本发明涉及上述组合物在制备用于防治酒精性肝损伤的药物中的应用。
第三方面，本发明涉及上述组合物在制备用于同时降低血清中谷丙转氨酶、谷草转氨酶、碱性磷酸酶、白蛋白、总蛋白、总胆红素的药物中的应用。
优选地，所述药物能制备成临床上可接受的口服给药制剂的形式。
第四方面，本发明涉及上述组合物在制备用于防治酒精性肝损伤的保健食品中的应用。
第五方面，本发明涉及上述组合物在制备用于同时降低血清中谷丙转氨酶(GPT)、谷草转氨酶(GOT)、碱性磷酸酶(ALP)、白蛋白(ALB)、总蛋白(TP)、总胆红素(TBIL)的保健食品中的应用。
优选地，所述保健食品能制备成临床上可接受的口服给药制剂的形式。
具体实施方式
下面结合实施例对本发明的技术方案做进一步描述。这些实施例仅用于说明本发明而不用于限定本发明的保护范围。
实施例1：药物对大鼠酒精性慢性肝损伤模型的影响
实验材料和方法
1.试验动物
雄性Wister大鼠，SPF级，体重140±10g，由中国医学科学院试验动物研究所提供，许可证号：scxk11-00-0006。
2.受试药物：
药物：由北京中医药大学药学院制剂室提供，每克(g)棕色粉末对应 5.7g生药。生药的配比如下：葛根花30g，白扁豆花30g，椇枳子10g，升麻 15g，姜黄15g，以及葛根15g。保存条件：常温密闭保存。
剂量设计：人临床用量为115g生药/60kg，即约2.0g生药/kg；实验中按人与大鼠等倍剂量换算，大鼠用量分别为20g生药/kg、10g生药/kg、5g 生药/kg(分别相当与人临床用量的2倍、等倍及和1/2倍(系数为5))，实验时按1ml/100g大鼠体重灌胃给药，对照组给蒸馏水1ml/100g大鼠体重灌胃。
阳性对照药：葵花牌护肝片，葵花药业产品。试验时大鼠采用8g/kg，灌胃给药，相当于人临床用药量的2倍。
4.试剂试剂和仪器(均为北京中生生物工程高技术公司产品)：
酒精，分析纯；
GPT、GOT、ALP、ALB、TP、TBIL检测试剂盒；
ZS-3型半自动生化分析仪
5.试验方法
取大鼠，除正常对照组外其余动物按0.5ml/100g体重，灌胃75％的酒精，每天1次，连续15天。第16天眼眶采血测定血清中GPT，去除GPT 含量低于100卡门单位的动物，其余动物根据GPT含量均匀分为5组：模型对照组、联苯双脂组、药物大、中、小剂量组，每组10只，另取10只做为正常对照组。分组后各组仍继续用75％的酒精造模，每周2次，连续8 周。给药组同时开始灌胃给药，每日1次，连续8周。正常对照组在同等情况下腹腔注射生理盐水和灌胃给蒸馏水。观察下列指标：
(1)每周称体重，记录死亡情况
(2)每2周检测血清中ALT含量
(3)分别于给药后6周、8周采血测定血清中ALT、AST、ALP、ALB、 TP、TBIL的含量
(4)病理检查
各指标采用组间比较T检验进行统计学处理。
6.试验结果
(1)对大鼠血清生化指标的影响：
表1中结果显示：药物大、中剂量组在给药第6周开始可明显降低血清中ALT含量；中剂量给药第6周开始、大小剂量给药第8周开始可明显降低血清中AST含量；大、中剂量组给药第8周可提高血清中ALB的含量；大、中剂量组给药第8周可降低血清中TBIL的含量，均与对照组比较有显著性差异(P<0.05或P<0.01)。药物对大鼠血清中ALP、TP含量无明显影响，结果见下表1；
(2)药物对CCL4慢性肝损伤模型大鼠的体重无明显影响，结果见下表2。
7.病理检验：
材料和方法：
7.1仪器：
7.2试剂：
甲醛溶液：北京市旭东化工厂生产(批号：2001023)，配成10％的浓度备用；乙醇：北京化工厂生产，(无水乙醇批号：20030929)，(95％乙醇批号：20031017)配成60％、70％、80％、100％的浓度备用；二甲苯：北京化工厂生产(批号：20030412)；苏木精：北京化学试剂公司生产(批号： 940727)；伊红(曙红)：北京化工厂生产(批号：810915)，两者各配成染液作HE染色；切片石蜡56～58℃：上海华灵康复器械厂生产(批号：20020129)；中性树脂胶：上海标本模型厂生产(批号：20000802)。
病理号：
7.3方法：
Wistar大鼠63只，分成6组：对照组、模型组、阳性药组、大剂量组、中剂量组、小剂量组。动物处死后解剖，立即摘取肝固定于10％福尔马林溶液中，取材后流水冲洗，梯度乙醇(60％、70％、80％、95％、100％)脱水，二甲苯透明，浸蜡包埋，切片，分别作HE染色和VG染色，光学树脂封片，光学显微镜下观察、照相。附显微照相彩色照片。
7.4结果
肉眼观察
对照组：肝组织颜色正常，表面光滑，大小硬度正常，切开断面无明显异常。
模型组：大部分肝脏明显肿大，重量增加，颜色深紫色，表面未见明显的渗出，颗粒较粗，切开包膜外翻，质地较硬。
给药不同剂量组；肝组织有不同程度的轻微肿胀，表面有细颗粒，未见有渗出。
镜下观察
HE染色
对照组：肝组织未见有脂肪变性、纤维增生及坏死，未见有炎性细胞浸润，组织结构正常。
模型组；大部分肝组织失去正常肝小叶的形态结构，可见中央静脉坏死、消失，或偏离中央，或结节出现一个以上。另外，中央静脉周围出现结缔组织增生，形成大小不等的假小叶，结缔组织间有明显的炎性细胞浸润，部分肝细胞内有散在的脂肪变性。假胆管增生不明显。
给药不同剂量组：与模型组比较肝组织纤维增生、汇管区的炎性细胞浸润、结节的形成均有减轻的趋势，尤其中、小剂量组的肝组织病变明显好于模型组，结果见下表3。
表3HE染色后肝组织病变程度
病变分级标准
—正常组织结构
+肝间质纤维组织增生及炎细胞浸润较局限
++肝间质纤维组织增生及炎细胞浸润呈大片状
+++，++++肝间质纤维组织增生及炎细胞浸润较弥漫
VG染色
切片经二甲苯再经各级酒精下行至蒸馏水，Weigert苏木精染后蒸馏水急洗，VanGieson(1％的酸性品红水溶液：苦味酸饱和水溶液为1：9)染， 95％酒精分色，`00％酒精脱水分色，二甲苯透明，封片。
对照组：肝组织间质纤维未见增生，组织结构正常。
模型组；大部分肝组织失去正常肝小叶的形态结构，出现结缔组织增生，染成紫红色，呈现强阳性结果。
给药不同剂量组：肝组织间质纤维VG染色呈弱阳性，中小剂量组肝组织纤维增生呈现明显的弱阳性。结果见下表4。
表4VG染色后肝组织病变程度
-肝组织中未见纤维组织增生
+肝间质纤维组织轻度增生，VG染色呈弱阳性
++，+++肝间质纤维组织明显增生，VG染色呈强阳性
实施例2：药物对小鼠酒精性急性肝损伤的保护作用
1.受试药物：由北京中医药大学药学院制剂室提供，每克(g)棕色粉末对应5.7g生药。生药的配比如下：葛根花30g，白扁豆花30g，椇枳子10g，升麻15g，姜黄15g，以及葛根15g。保存条件：常温密闭保存。
2.试验动物：雄性ICR小鼠，SPF级，体重19±10g，由北京维通利华试验动物技术研究所提供，许可证号：scxk京-2002-0003。
3.剂量设计：人临床用量为115g生药/60kg，即约2.0g生药/kg；实验中按人与小鼠等倍剂量换算，小鼠用量分别为40g生药/kg、20g生药/kg、 10g生药/kg(分别相当与人临床用量的2倍、等倍及和1/2倍(系数为10))，实验时按0.2ml/10g小鼠体重灌胃给药，对照组给蒸馏水0.2ml/10g小鼠体重灌胃。
4.阳性对照药：葵花护肝片，葵花药业产品。试验时小鼠采用16g/kg，灌胃给药，相当于人临床用药量的2倍。
5.试剂仪器：酒精，分析纯，75％；GPT、ALP检测试剂盒，ZS-3型半自动生化分析仪均为北京中生生物工程高技术公司产品。
6.试验结果：
取小鼠60只，按体重分为正常对照组、模型对照组、葵花护肝片组、药物大、中、小剂量组，各给药组灌胃给药，每日一次，连续5天。给药第4天下午除正常对照组外其余动物按0.2ml/10g体重，90％酒精一次，48 小时后各动物采血，测定GPT含量。参见下表5的结果，显示药物大、中剂量组可明显降低小鼠酒精性急性肝损伤的GPT含量，其中大剂量组与模型对照组比较有显著性差异(P<0.05)。
表5药物对小鼠急性肝损伤的保护作用
与模型组比较*P<0.05。
Claims (10)
1.组合物，所述组合物包括葛根花、白扁豆花、棋枳子、升麻、姜黄和葛根。
2.根据权利要求1的组合物，其以重量份计的配方如下：葛根花5-60重量份，白扁豆花5-30重量份，棋枳子5-30重量份，升麻5-30重量份，姜黄5-60重量份。
3.根据权利要求1的组合物，其中组合物的配比如下：葛根花30g，白扁豆花30g，棋枳子10g，升麻15g，姜黄15g，以及葛根15g。
4.根据权利要求1或2的组合物，其可制成保健食品及临床或药学上可接受的片剂、胶囊剂、颗粒剂、口服液、固体饮料、液体饮料的形式。
5.权利要求1-4任一项所述的组合物在制备用于防治酒精性肝损伤的药物中的应用。
6.权利要求1-4任一项所述的组合物在制备用于同时降低血清中谷丙转氨酶、谷草转氨酶、碱性磷酸酶、白蛋白、总蛋白、总胆红素的药物中的应用。
7.根据权利要求5或6的应用，其特征在于，所述药物能制备成临床上可接受的口服给药制剂的形式。
8.权利要求1-4任一项所述的组合物在制备用于防治酒精性肝损伤的保健食品中的应用。
9.权利要求1-4任一项所述的组合物在制备用于同时降低血清中谷丙转氨酶、谷草转氨酶、碱性磷酸酶、白蛋白、总蛋白、总胆红素的保健食品中的应用。
10.根据权利要求8或9的应用，其特征在于，所述保健食品能制备成临床上可接受的口服给药制剂的形式。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811165485.4A CN109985206A (zh) | 2018-09-30 | 2018-09-30 | 用于防治酒精性肝损伤的组合物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811165485.4A CN109985206A (zh) | 2018-09-30 | 2018-09-30 | 用于防治酒精性肝损伤的组合物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109985206A true CN109985206A (zh) | 2019-07-09 |
Family
ID=67128422
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811165485.4A Pending CN109985206A (zh) | 2018-09-30 | 2018-09-30 | 用于防治酒精性肝损伤的组合物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109985206A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113559152A (zh) * | 2021-09-27 | 2021-10-29 | 北京本草源生物科技有限公司 | 护肝中药组合物、饮品及其制备方法和应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1969985A (zh) * | 2005-11-25 | 2007-05-30 | 宋和敬 | 一种解酒冲剂的生产方法 |
-
2018
- 2018-09-30 CN CN201811165485.4A patent/CN109985206A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1969985A (zh) * | 2005-11-25 | 2007-05-30 | 宋和敬 | 一种解酒冲剂的生产方法 |
Non-Patent Citations (2)
| Title |
|---|
| 彭景华等: "健脾活血方对酒精复合内毒素脂多糖诱导的肝损伤大鼠库普弗细胞活化信号通路的干预", 《中西医结合学报》 * |
| 曹健美等: "健脾理气活血方对酒精性肝损伤大鼠血浆内毒素和TNF-α蛋白表达的影响", 《上海中医药大学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113559152A (zh) * | 2021-09-27 | 2021-10-29 | 北京本草源生物科技有限公司 | 护肝中药组合物、饮品及其制备方法和应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106474145B (zh) | 辣木叶多糖在制备防治酒精性肝损伤药物和食品中的应用 | |
| CN107441078A (zh) | 一种治疗糖尿病的药物组合物及其制备方法和用途 | |
| CN104689251A (zh) | 一种缓解化学性肝损伤的中药组合物、其制备方法及中药制剂 | |
| CN102697781B (zh) | 胡芦巴碱作为制备防治糖尿病及其并发症药物的应用 | |
| WO2008037222A1 (en) | A hypolipidemic composition and its use | |
| CN109985206A (zh) | 用于防治酒精性肝损伤的组合物 | |
| CN101167781A (zh) | 口服降血糖红薯叶单方中药及其制备方法 | |
| CN103977390B (zh) | 一种生姜洋葱药酒组合物的制备方法及其用途 | |
| CN101816719B (zh) | 桃花或桃叶总黄酮及它们在制备降血糖血脂、预防和/或治疗糖尿病及并发症药物或保健品中的用途 | |
| CN107041924A (zh) | 一种防治糖尿病肾病的朝药复方提取物及其制备方法 | |
| CN103432420B (zh) | 一种治疗糖尿病的中药组合物及其制备方法和检测方法 | |
| CN102309705B (zh) | 一种降低血尿酸的药物及其制备方法和用途 | |
| CN104042928B (zh) | 一种治疗糖尿病的药物组合物及其制备方法和用途 | |
| CN1272290C (zh) | 栀子环烯醚萜总提物及其制备方法和用途 | |
| CN102258557B (zh) | 一种用于治疗前列腺增生的药物 | |
| CN102430001B (zh) | 防治糖尿病的复方蔷薇果黄酮制剂及其制备方法 | |
| CN101658576B (zh) | 化橘红总黄酮在制备治疗酒精性肝损伤的药物中的用途 | |
| CN101269152A (zh) | 枸杞子和黑木耳在制备抗脂肪肝药物中的应用 | |
| CN1298351C (zh) | 一种治疗泌尿系感染的中药口服制剂及其制备方法 | |
| CN1466951A (zh) | 栀子环烯醚萜总提物药物组合物制剂及其制备方法和用途 | |
| CN105535070B (zh) | 治疗糖尿病的药物组合物及其制备方法和应用 | |
| CN103191224A (zh) | 荷丹制剂的保肝护肝作用 | |
| CN104127545B (zh) | 四数九里香及其提取物在制备药物中的应用 | |
| CN103272079B (zh) | 一种治疗糖尿病肾病的回药复方及其应用 | |
| CN102526203B (zh) | 一种具有抗糖尿病肾病作用的香椿子提取物制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |