CN114177225A - 一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用 - Google Patents
一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用 Download PDFInfo
- Publication number
- CN114177225A CN114177225A CN202110990464.1A CN202110990464A CN114177225A CN 114177225 A CN114177225 A CN 114177225A CN 202110990464 A CN202110990464 A CN 202110990464A CN 114177225 A CN114177225 A CN 114177225A
- Authority
- CN
- China
- Prior art keywords
- oyster
- traditional chinese
- chinese medicine
- kudzu root
- hyperlipidemia
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 75
- 235000010575 Pueraria lobata Nutrition 0.000 title claims abstract description 56
- 208000031226 Hyperlipidaemia Diseases 0.000 title claims abstract description 51
- 150000001875 compounds Chemical class 0.000 title claims abstract description 49
- 241000237502 Ostreidae Species 0.000 title claims abstract description 47
- 235000020636 oyster Nutrition 0.000 title claims abstract description 47
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- 241000219781 Pueraria montana var. lobata Species 0.000 title abstract 3
- 244000046146 Pueraria lobata Species 0.000 claims abstract description 53
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 28
- 239000008187 granular material Substances 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 239000000843 powder Substances 0.000 claims description 18
- 244000302512 Momordica charantia Species 0.000 claims description 14
- 235000009811 Momordica charantia Nutrition 0.000 claims description 14
- 229920001353 Dextrin Polymers 0.000 claims description 12
- 239000004375 Dextrin Substances 0.000 claims description 12
- 229920002472 Starch Polymers 0.000 claims description 12
- 235000019425 dextrin Nutrition 0.000 claims description 12
- 235000019698 starch Nutrition 0.000 claims description 12
- 239000008107 starch Substances 0.000 claims description 12
- 235000009917 Crataegus X brevipes Nutrition 0.000 claims description 11
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 claims description 11
- 235000009685 Crataegus X maligna Nutrition 0.000 claims description 11
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 claims description 11
- 235000009486 Crataegus bullatus Nutrition 0.000 claims description 11
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 claims description 11
- 235000009682 Crataegus limnophila Nutrition 0.000 claims description 11
- 240000000171 Crataegus monogyna Species 0.000 claims description 11
- 235000004423 Crataegus monogyna Nutrition 0.000 claims description 11
- 235000002313 Crataegus paludosa Nutrition 0.000 claims description 11
- 235000009840 Crataegus x incaedua Nutrition 0.000 claims description 11
- 235000009812 Momordica cochinchinensis Nutrition 0.000 claims description 11
- 235000018365 Momordica dioica Nutrition 0.000 claims description 11
- 239000002994 raw material Substances 0.000 claims description 9
- 238000000227 grinding Methods 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 235000008322 Trichosanthes cucumerina Nutrition 0.000 claims description 3
- 201000005577 familial hyperlipidemia Diseases 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 210000004185 liver Anatomy 0.000 abstract description 23
- 108010028554 LDL Cholesterol Proteins 0.000 abstract description 16
- 102000004889 Interleukin-6 Human genes 0.000 abstract description 15
- 108090001005 Interleukin-6 Proteins 0.000 abstract description 15
- 108010023302 HDL Cholesterol Proteins 0.000 abstract description 14
- 206010061218 Inflammation Diseases 0.000 abstract description 13
- 230000004054 inflammatory process Effects 0.000 abstract description 13
- 102000003945 NF-kappa B Human genes 0.000 abstract description 12
- 108010057466 NF-kappa B Proteins 0.000 abstract description 12
- 210000004369 blood Anatomy 0.000 abstract description 12
- 239000008280 blood Substances 0.000 abstract description 12
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 11
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract description 11
- 210000005228 liver tissue Anatomy 0.000 abstract description 11
- 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 abstract description 10
- 238000001727 in vivo Methods 0.000 abstract description 9
- 150000002632 lipids Chemical class 0.000 abstract description 9
- 230000004913 activation Effects 0.000 abstract description 7
- 210000004969 inflammatory cell Anatomy 0.000 abstract description 7
- 230000002757 inflammatory effect Effects 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 7
- 230000006907 apoptotic process Effects 0.000 abstract description 6
- 230000006378 damage Effects 0.000 abstract description 5
- 210000003989 endothelium vascular Anatomy 0.000 abstract description 5
- 230000008595 infiltration Effects 0.000 abstract description 5
- 238000001764 infiltration Methods 0.000 abstract description 5
- 229940126680 traditional chinese medicines Drugs 0.000 abstract description 3
- 230000000694 effects Effects 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 14
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 11
- 108010082126 Alanine transaminase Proteins 0.000 description 11
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 11
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 210000005229 liver cell Anatomy 0.000 description 10
- 229960002297 fenofibrate Drugs 0.000 description 9
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000011246 composite particle Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 210000003494 hepatocyte Anatomy 0.000 description 5
- 238000010298 pulverizing process Methods 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 4
- 210000000683 abdominal cavity Anatomy 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000002055 immunohistochemical effect Effects 0.000 description 3
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- 206010062717 Increased upper airway secretion Diseases 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 244000179886 Moringa oleifera Species 0.000 description 2
- 235000011347 Moringa oleifera Nutrition 0.000 description 2
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 240000000851 Vaccinium corymbosum Species 0.000 description 2
- 235000003095 Vaccinium corymbosum Nutrition 0.000 description 2
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000021014 blueberries Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000003960 inflammatory cascade Effects 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 208000026435 phlegm Diseases 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 240000002900 Arthrospira platensis Species 0.000 description 1
- 235000016425 Arthrospira platensis Nutrition 0.000 description 1
- UYIFTLBWAOGQBI-BZDYCCQFSA-N Benzhormovarine Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3OC(=O)C1=CC=CC=C1 UYIFTLBWAOGQBI-BZDYCCQFSA-N 0.000 description 1
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 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 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000035762 Disorder of lipid metabolism Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 244000061508 Eriobotrya japonica Species 0.000 description 1
- 235000009008 Eriobotrya japonica Nutrition 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 1
- 102100022119 Lipoprotein lipase Human genes 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 1
- 101100366137 Mesembryanthemum crystallinum SODCC.1 gene Proteins 0.000 description 1
- 240000000249 Morus alba Species 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101100096142 Panax ginseng SODCC gene Proteins 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 229920001100 Polydextrose Polymers 0.000 description 1
- 206010067171 Regurgitation Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003460 anti-nuclear Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 229940074393 chlorogenic acid Drugs 0.000 description 1
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 1
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 1
- 235000001368 chlorogenic acid Nutrition 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000009123 feedback regulation Effects 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 1
- 229960004999 lycopene Drugs 0.000 description 1
- 239000001751 lycopene Substances 0.000 description 1
- 235000012661 lycopene Nutrition 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 239000001259 polydextrose Substances 0.000 description 1
- 235000013856 polydextrose Nutrition 0.000 description 1
- 229940035035 polydextrose Drugs 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 101150017120 sod gene Proteins 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229940082787 spirulina Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000005982 spleen dysfunction Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
-
- 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)
- A61K36/42—Cucurbitaceae (Cucumber family)
-
- 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)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/734—Crataegus (hawthorn)
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Botany (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Marine Sciences & Fisheries (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明涉及中药技术领域,具体是一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用。本发明的牡蛎葛根复方中药组合物能够改善体内脂类物质,使体内HDL‑C升高,而LDL‑C下降,减少血管内皮上的系列炎症反应,减少细胞凋亡,减轻机体高脂血症的炎症状态;本发明的牡蛎葛根复方中药组合物能够减少高脂血症对肝脏的损害,保护肝脏,降低血液中的ALT、AST水平;本发明的牡蛎葛根复方中药组合物能够有效抑制TNF‑α、IL‑6、NF‑κB的活化可以有效抑制机体的炎症反应,进而缓解高脂血症的进展,减少高脂血症中肝脏组织炎症细胞浸润。
Description
技术领域
本发明涉及中药技术领域,具体是一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用。
背景技术
高血脂症(hyperlipemia,HLP)是指机体受到年龄,性别,生活习惯等因素影响,引起体内脂质代谢紊乱,进而造成血液中脂质水平异常。临床主要表现为总胆固醇(totalcholesterol,TC),甘油三酯(triglyceride,TG),低密度脂蛋白胆固醇(low densitylipoprotein cholesterol,LDL-C)的异常升高,高密度胆固醇(high densitylipoprotein cholesterol,HDL-C)的异常降低。诱发高血脂症的因素较多,不良生活习惯及基础疾病是诱发高血脂症的重要因素,如摄入高脂肪食物,高血压等。高血脂症是诱发动脉粥样硬化的直接因素。而动脉粥样硬化是诱发心脑血管疾病的直接因素。轻症或早期高血脂症,首选非药物治疗。经过非药物治疗未取得理想效果的患者,选择药物治疗。目前,药物治疗是临床上治疗高血脂症的主要途径。临床常用于调节血脂的药物有他汀类和贝特类药物。然而,这两种药物存在诸多的不良反应,部分患者不能耐受。
中医认为高血脂症是血浊病、“膏”病等,病机为肝失疏泄,脾失健运,肾精亏虚,痰瘀内阻,治疗方法主要为理肝调脾,化痰湿浊,活血化瘀。
牡蛎,俗称生蚝,肉质鲜嫩,富含丰富的蛋白质和锌,具有增强免疫力,保肝,降血糖,延缓衰老,抗肿瘤等药用价值。然而人们在食用牡蛎肉之后,将坚硬得外壳视作废弃物直接丢弃,既成为环境治理的棘手问题,又浪费大量海洋生物资源。牡蛎壳主要成分有碳酸钙,微量元素及氨基酸等,具有治疗惊厥,失眠,眩晕耳鸣,自汗盗汗,胃痛吞酸等功效。然而,由于牡蛎壳质地坚硬,其中的有效成分溶解性差,吸收率低,在医药卫生领域一直未能得到充分有效开发。因此,牡蛎壳的二次开发利用成为医药卫生领域及环保领域的关键问题。
通过文献调研发现,目前尚未有文献报道牡蛎葛根复方中药组合物对高血脂症治疗的相关研究。
并且,目前虽然有使用中药降血脂的技术方案,但是其主要是通过降低胆固醇的吸收并促进其排泄来进行,如专利申请 CN201610684144.2(一种具有降血脂功效的辣木叶蓝莓复合果汁及其制备方法),其是由蓝莓果140-145、煅烧牡蛎壳19-20、绿原酸11-12、辣木叶34-35、桑叶32-33、枇杷叶31-32、益生菌9-10、螺旋藻超微粉 29-30、番茄红素8-9、聚葡萄糖9-10、山梨糖醇11-12、赤藓糖醇10-11 等组成,其并不具有降低LDL-C,升高HDL-C;保护肝脏,减少肝损伤;抑制促炎因子的活化,抑制集体炎症反应等效果,无法全方位的对高脂血症产生治疗效果。而且目前使用中药降血脂的技术方案,对血脂的影响效果并不突出,达不到目前高脂血症常用药物的效果。
发明内容
为了解决现有技术中存在的上述技术问题,本发明提供一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用。具体是通过以下技术方案得以实现的:
一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用,所述中药组合物由如下重量份数的原料制备得到:牡蛎壳10-15份、苦瓜干15-25份、葛根15-25份、山楂15-25份。进一步的,所述各原料重量份数为:牡蛎壳12份、苦瓜干20份、葛根20份、山楂20份。
进一步的,还可以将该牡蛎葛根复方中药组合物作为原料之一,与其他组分共同来制备治疗/预防高脂血症药物。
进一步的,所述牡蛎壳,是300目的牡蛎壳粉。
进一步的,所述治疗/预防高脂血症药物,为颗粒剂。所述颗粒剂,是向原料中加入辅料后制备成颗粒得到,所用辅料重量占颗粒重量的15-25%。并且,所述辅料,是淀粉和糊精。
所述复方中药组合物通过以下步骤进行制备:
(1)取牡蛎壳、苦瓜干、葛根、山楂备用;
(2)将牡蛎壳研成细粉,待用;
(3)苦瓜干、葛根、山楂粉碎,然后加水共同煎煮2~3次,浓缩成稠膏;
(4)将步骤(3)所得稠膏烤成干膏,粉碎,加牡蛎壳粉,混合均匀,即得。还可以向所得产品中加入辅料,直接制成颗粒剂成品。
进一步的,所述步骤(3)的加水共同煎煮2~3次,具体是加水共同煎煮2次,第一次加水10倍量,第二次加水8倍量,每次煎煮 2小时。
进一步的,所述步骤(3)的浓缩成稠膏,具体是煎煮完成后,合并煎液,滤过,浓缩成稠膏。
与现有技术相比,本发明创造的技术效果体现在:
(1)本发明的牡蛎葛根复方中药组合物能够改善体内脂类物质,使体内HDL-C升高,而LDL-C下降,减少血管内皮上的系列炎症反应,减少细胞凋亡,减轻机体高脂血症的炎症状态。
(2)本发明的牡蛎葛根复方中药组合物能够减少高脂血症对肝脏的损害,保护肝脏,降低血液中的ALT、AST水平。
(3)本发明的牡蛎葛根复方中药组合物能够有效抑制TNF-α、 IL-6、NF-κB的活化可以有效抑制机体的炎症反应,进而缓解高脂血症的进展,减少高脂血症中肝脏组织炎症细胞浸润。
(4)本发明的牡蛎葛根复方中药组合物所制备得到的颗粒剂在治疗高脂血症方面,效果已接近非诺贝特,具有良好的效果,远高于本申请中各原料药物单独使用的效果。
附图说明
图1是对高血脂症小鼠肝脏病理学的影响图(小鼠肝脏组织H&E 染色(×200)):;A:正常对照组;B:模型对照组;C:非诺贝特阳性对照组;D:牡蛎葛根复方中药高剂量组;E:牡蛎葛根复方中药中剂量组;F:牡蛎葛根复方中药低剂量组。
图2是对小鼠肝脏组织中NF-κB、TNF-α、IL-6蛋白表达的影响 (×400)图:A:正常对照组;B:模型对照组;C:非诺贝特阳性对照组;D:牡蛎葛根复方中药高剂量组;E:牡蛎葛根复方中药中剂量组;F:牡蛎葛根复方中药低剂量组。
具体实施方式
下面结合具体的实施方式来对本发明的技术方案做进一步的限定,但要求保护的范围不仅局限于所作的描述。
实施例1
牡蛎葛根复合颗粒,通过以下步骤制备:
(1)取牡蛎壳1.2kg、苦瓜干2kg、葛根2kg、山楂2kg备用;
(2)将牡蛎壳研成细粉(300目),待用;
(3)苦瓜干、葛根、山楂粉碎,然后加水共同煎煮2次,第一次加水10倍量,第二次加水8倍量,每次煎煮2小时,煎煮完成后,合并煎液,滤过,浓缩成稠膏;
(4)将步骤(3)所得稠膏烤成干膏,粉碎,加牡蛎壳粉、淀粉、糊精,其中淀粉为颗粒重量的20%、糊精为颗粒重量的1.5%,制成颗粒。
实施例2
牡蛎葛根复合颗粒,通过以下步骤制备:
(1)取牡蛎壳1kg、苦瓜干2.5kg、葛根2.5kg、山楂2.5kg备用;
(2)将牡蛎壳研成细粉(300目),待用;
(3)苦瓜干、葛根、山楂粉碎,然后加水共同煎煮2次,第一次加水10倍量,第二次加水8倍量,每次煎煮2小时,煎煮完成后,合并煎液,滤过,浓缩成稠膏;
(4)将步骤(3)所得稠膏烤成干膏,粉碎,加牡蛎壳粉、淀粉、糊精,其中淀粉为颗粒重量的20%、糊精为颗粒重量的1.5%,制成颗粒。
实施例3
牡蛎葛根复合颗粒,通过以下步骤制备:
(1)取牡蛎壳1.5kg、苦瓜干1.5kg、葛根1.5kg、山楂1.5kg备用;
(2)将牡蛎壳研成细粉(300目),待用;
(3)苦瓜干、葛根、山楂粉碎,然后加水共同煎煮2次,第一次加水10倍量,第二次加水8倍量,每次煎煮2小时,煎煮完成后,合并煎液,滤过,浓缩成稠膏;
(4)将步骤(3)所得稠膏烤成干膏,粉碎,加牡蛎壳粉、淀粉、糊精,其中淀粉为颗粒重量的20%、糊精为颗粒重量的1.5%,制成颗粒。
实施例4
牡蛎葛根复合颗粒,通过以下步骤制备:
(1)取牡蛎壳1.2kg、苦瓜干2kg、葛根2kg、山楂2kg备用;
(2)将牡蛎壳研成细粉(200目),待用;
(3)苦瓜干、葛根、山楂粉碎,然后加水共同煎煮2次,第一次加水10倍量,第二次加水8倍量,每次煎煮2小时,煎煮完成后,合并煎液,滤过,浓缩成稠膏;
(4)将步骤(3)所得稠膏烤成干膏,粉碎,加牡蛎壳粉、淀粉、糊精,其中淀粉为颗粒重量的23%、糊精为颗粒重量的2%,制成颗粒。
实施例5
牡蛎葛根复合颗粒,通过以下步骤制备:
(1)取牡蛎壳1.2kg、苦瓜干2kg、葛根2kg、山楂2kg备用;
(2)将牡蛎壳研成细粉(400目),待用;
(3)苦瓜干、葛根、山楂粉碎,然后加水共同煎煮2次,第一次加水10倍量,第二次加水8倍量,每次煎煮2小时,煎煮完成后,合并煎液,滤过,浓缩成稠膏;
(4)将步骤(3)所得稠膏烤成干膏,粉碎,加牡蛎壳粉、淀粉、糊精,其中淀粉为颗粒重量的14%、糊精为颗粒重量的1%,制成颗粒。
以实施例1所得以牡蛎葛根复方中药组合物制成的颗粒剂为主要受试物,通过建立动物模型及测定相关的生化、病理和免疫组化指标,说明对高脂血症的治疗效果及作用机制。
1材料与方法
1.1动物
昆明种小鼠,SPF级,雌雄各半,体质量(20±2)g。购买自广西医科大学实验动物中心。动物饲养于通风条件良好,温度在 18~25℃,相对湿度在40%~70%,12h光照昼夜循环的环境。试验动物生产许可证:SCXK桂2014-0002,试验动物使用许可证:SYXK桂 2014-0003。
1.2试验药物选择
使用实施例1所得以牡蛎葛根复方中药组合物制成的颗粒剂作为试验药物,牡蛎葛根颗粒成分中的苦瓜、葛根以及红枣都属于药食两用植物;而牡蛎是广西北海市特产,中国国家地理标志产品。组方中的药材均由本课题组采购自广西医科大学“试剂耗材采购管理平台”。
1.3试剂与仪器
非诺贝特,法国利博福尼制药公司;Triton WR-1339,Sigma公司;LDL-C、HDL-C、TC、TG、ALT、AST、SOD、MDA、NO、T-NOS 试剂盒,南京建成生物工程研究;通用SP试剂盒:上海雅吉生物技术有限公司;兔抗核转录因子κB(NF-κB)、肿瘤坏死因子α(TNF- α)、白介素6(IL-6)抗体:Cell Signaling Technology;通用二抗, Thermo Fisher Scientific;酶标仪:Beckman公司;显微镜:OLYMPUS;切片机、病理图像分析仪:德国LEICA公司;
1.4动物分组、给药及模型建立
将60只小鼠随机分为6组,每组10只。适应性喂养3d后,按照下列给药剂量给予相应药物14d(每天给药1次,固定上午10时给药):正常对照组:生理盐水;模型对照组:生理盐水;非诺贝特阳性对照组:非诺贝特,0.03g/kg;牡蛎葛根复方中药高剂量组:10 g/kg;牡蛎葛根复方中药中剂量组:5g/k;牡蛎葛根复方中药低剂量组:0.25g/kg。给药容量为20ml/kg。末次给药后1h,正常对照组经腹腔注射10ml/kg生理盐水外,其余各组小鼠腹腔注射等剂量600 mg/kg TritonWR-1339,构建高血脂症模型。
TritonWR-1339,又称四酚丁醛,是一种非离子型表面活性剂,现常作为实验性高血脂症的诱导剂,广泛应用于降脂药物的筛选。 TritonWR-1339通过抑制脂蛋白脂肪酶的活性,可在短时间内引起机体血清TC及TG异常,具有操作简便,迅速的优点。本研究的造模方案为一次性腹腔注射600mg/kg TritonWR-1339,造模时间为24h。
1.5动物处置及标本制备
采用10%水合氯醛麻醉小鼠,采集小鼠血浆,收集上层血清, -80℃保存备用。收集小鼠肝脏,立即取小鼠肝脏右叶1m3大小的组织,浸泡于4%甲醛溶液中。将剩余部分存放于液氮中,备用。
1.6指标检测
1.6.1血清生化指标的检测
收集小鼠血清,严格按照试剂盒的说明检测血清中TC、TG、 LDL-C、HDL-C、谷草转氨酶(AST)、谷丙转氨酶(ALT)、总一氧化氮合酶(T-NOS)的水平。
1.6.2肝组织病理学检查
肝组织经4%甲醛固定24h后,常规脱水,石蜡包埋,行HE染色,200倍光镜下观察组织形态。
1.6.3免疫组化法检测肝脏组织中TNF-α、NF-κB、IL-6蛋白的表达
取出肝组织,进行常规石蜡包埋,切片。按照免疫组化的步骤滴加TNF-α(稀释比例分别为1:800)、NF-κB(稀释比例分别为1: 1000)、IL-6(稀释比例分别为1:600)一抗,4℃孵育过夜,二抗(稀释比例分别为1:10000)孵育2h,PBS冲洗5次后染色,封片,阅片。
1.7统计学方法
应用SPSS21.0软件进行统计分析。进行描述性统计分析后根据正态分布及方差齐性检验,两组间的比较用t检验(t-test),多组间的比较用方差分析(ONE-WAYANOVA),方差不齐则采用秩和检验方法进行统计分析,P<0.05则表示有统计学差异。
2结果
2.1牡蛎葛根复方中药对高血脂症小鼠血清中HDL-C、LDL-C水平的影响
由表1可知,模型组小鼠血清中HDL-C的水平较正常对照组显著下降(P<0.05),LDL-C水平较正常对照组显著升高(P<0.01)。经过牡蛎葛根复方中药干预后,牡蛎葛根复方中药高、中、低剂量组的HDL-C显著升高(P<0.05),而LDL-C显著下降(P<0.05或P<0.01)。
与正常对照相比,*P<0.05,**P<0.01;与模型对照组相比,#P<0.05,##P<0.01
2.2牡蛎葛根复方中药对高血脂症小鼠血清中AST、ALT水平的影响
由表2可知,与正常对照组相比,高血脂症模型组小鼠血清中的 AST、ALT值显著升高(P<0.05或P<0.01)。与高血脂症模型组小鼠相比较,非诺贝特阳性对照组,牡蛎葛根复方中药高、中剂量组小鼠血清AST、ALT值显著下调(P<0.05或P<0.01)。牡蛎葛根复方中药低剂量组的改变尚未达到显著性差异(P>0.05)。
与正常对照相比,*P<0.05,**P<0.01;与模型对照组相比,#P<0.05,##P<0.01
2.3牡蛎葛根复方中药对高血脂症小鼠肝脏病理学的影响
由附图1可以看出,正常对照组小鼠肝细胞结构完整,清晰,呈放射状分布,无明显炎症浸润,变形等病理学改变。HLP模型组可见大量肝细胞损伤,变形,溶解,呈空泡状;少数肝细胞可见核仁存在,但核仁明显肿胀,变形。肝索膨大,周围肝细胞排列混乱,已失去原有的放射状。同时,可见大量脂滴分布,挤压周围的肝细胞,致使肝细胞变形。非诺贝特阳性对照组,牡蛎葛根复方中药高、中剂量组较 HLP模型组明显好转,未见大量炎性细胞侵润,肝细胞较完整,清晰,可见肝索周围的肝细胞基本呈反射状分布,核仁呈圆形或椭圆形,均匀分布;少见脂滴分布。牡蛎葛根复方中药低剂量组肝细胞较完整,清晰,但是可见肝索及周围肝细胞变性,排序混乱,少量炎症细胞侵润。同时可见脂滴分布,情况较中、高剂量组稍差,但相对于模型组稍好。
2.4高血脂症小鼠肝脏组织中NF-κB、TNF-α及IL-6蛋白表达水平
由附图2可看出,NF-κB的阳性(棕色)表达主要位于肝细胞胞膜,TNF-α的阳性(棕色)表达主要分布在肝细胞的胞浆及胞膜上,IL-6的阳性(棕色)表达主要位于胞膜及细胞间隙中。由图2A 可以看出,正常对照组几乎无或少有阳性表达。模型组NF-κB、TNF- α及IL-6的阳性表达量较正常对照组明显丰富(附图2B)。阳性对照组的阳性表达量较模型组减少,仅TNF-α见少数肝细胞的胞膜被染成浅棕色(附图2C)。牡蛎葛根复方中药三个剂量组的阳性表达量相对模型组明显减少,与阳性对照组的表达量基本持平(附图2D、 E、F)。
3结论
(1)高血脂症时机体内脂类物质发生显著改变,TC、TG、LDL-C 水平异常升高,HDL-C水平异常降低,以上指标常作为评价高血脂症的“金标准”。在诸多危险因素中,LDL-C的升高被认为是最危险的因素。LDL-C积蓄于血管内皮上,在氧化因子的作用下,进一步氧化形成氧化型LDL(ox-LDL)。ox-LDL可触发血管内皮上的系列炎症反应及细胞凋亡,加重机体的炎症状态。因此,LDL-C被认为是不利因素。而HDL-C则与之相反,在高脂血症时,其呈现低表达状态,被认为是有利因素。实验结果说明,本发明的牡蛎葛根复方中药组合物能够改善体内脂类物质,使体内HDL-C升高,而LDL-C下降,减少血管内皮上的系列炎症反应,减少细胞凋亡,减轻机体高脂血症的炎症状态。
(2)肝脏,小肠等机体多数器官参与TG的合成与代谢,其中以肝脏合成能力最强。因此,通过检测肝脏功能,了解高血脂症的进程是必要的。经tritonWR-1339诱导,小鼠血清ALT及AST水平较正常对照组异常升高,表明在高血脂症发生的同时伴随着肝脏的损害,同时异常升高的脂质可反向加重肝脏的脂代谢负担,进一步加剧肝脏细胞的损伤,阻碍脂代谢。二者相互作用,使得高血脂症和肝损伤恶性循环。而牡蛎葛根复方中药给药组小鼠血清ALT、AST水平较模型组显著下调,说明牡蛎葛根复方中药具有护肝的功效,能够减少高脂血症对肝脏的损害,保护肝脏,降低血液中的ALT、AST水平。
(3)炎症反应是机体抵御外界有害物质侵入机体的常见病理过程,控制炎症对于维持机体的正常代谢功能及抑制疾病的进展具有重要意义。研究表明TNFα的激活与肝脏病变存在密切联系。NF-κB 是炎症反应,免疫调节等过程的重要介质,是调节细胞增殖,凋亡过程的重要因子。促炎因子的激活导致炎症因子如NF-κB及其下游因子的释放,引发机体炎症级联反应。TNFα是由多种细胞产生的中枢炎症促进细胞因子,是控制炎症过程的关键所在。IL-6是由单核巨噬细胞,B细胞,T细胞等多种细胞分化产生的具备多种生物效应功能的多细胞因子,在免疫反应,细胞的分化增殖与凋亡的过程中占据重要地位。当上游刺激因子如TNF-α被激活时,IκB发生磷酸化反应,激活NF-κB。活化的NF-κB因子核定位序列被暴露,转录到核内特定位点,启动基因转录程序,产生或激活下游的其他因子。与此同时下游其他因子又可以反向激活NF-κB因子,形成反馈调节模式,从而使炎症级联反应扩大,加剧疾病的进展。Triton WR1339诱导剂作为外源性物质注射到小鼠体内,激活TNF-α、IL-6等促炎因子及NF- κB炎症因子。因此,有效抑制TNF-α、IL-6、NF-κB的活化可以有效抑制机体的炎症反应,进而缓解疾病的进展。从病理切片图可以看出,tritonWR1339诱导后,模型组小鼠肝索周围可见大量炎症细胞侵润,肝细胞变性,坏死。牡蛎葛根复方中药高、中、低剂量组少见炎症细胞侵润。从免疫组化结果可看出,模型组小鼠肝脏组织中NF- κB、TNF-α、IL-6表达量较正常对照组明显丰富,而牡蛎葛根复方中药给药组的表达量较模型组明显减少。说明本发明的牡蛎葛根复方中药组合物能够有效抑制TNF-α、IL-6、NF-κB的活化,可以有效抑制机体的炎症反应,进而缓解高脂血症的进展,减少高脂血症中肝脏组织炎症细胞浸润。
(4)本发明的牡蛎葛根复方中药组合物所制备得到的颗粒剂在治疗高脂血症方面,效果已接近非诺贝特,具有良好的效果。
最后,应当指出,以上实施例仅是本发明较有代表性的例子。显然,本发明的技术方案并不限于上述实施例,还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形,均应认为是本发明的保护范围。
Claims (9)
1.一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用,其特征在于,所述中药组合物由如下重量份数的原料制备得到:牡蛎壳10-15份、苦瓜干15-25份、葛根15-25份、山楂15-25份。
2.根据权利要求1所述的应用,其特征在于,所述各原料重量份数为:牡蛎壳12份、苦瓜干20份、葛根20份、山楂20份。
3.根据权利要求1所述的应用,其特征在于,所述牡蛎壳,是300目的牡蛎壳粉。
4.根据权利要求1所述的应用,其特征在于,所述治疗/预防高脂血症药物,为颗粒剂。
5.根据权利要求4所述的应用,其特征在于,所述颗粒剂,是向原料中加入辅料后制备成颗粒得到,所用辅料重量占颗粒重量的15-25%。
6.根据权利要求5所述的应用,其特征在于,所述辅料,是淀粉和糊精。
7.根据权利要求1所述的应用,其特征在于,所述复方中药组合物通过以下步骤进行制备:
(1)取牡蛎壳、苦瓜干、葛根、山楂备用;
(2)将牡蛎壳研成细粉,待用;
(3)苦瓜干、葛根、山楂粉碎,然后加水共同煎煮2~3次,浓缩成稠膏;
(4)将步骤(3)所得稠膏烤成干膏,粉碎,加牡蛎壳粉,混合均匀。
8.根据权利要求8所述的应用,其特征在于,所述步骤(3)的加水共同煎煮2~3次,具体是加水共同煎煮2次,第一次加水10倍量,第二次加水8倍量,每次煎煮2小时。
9.根据权利要求8所述的应用,其特征在于,所述步骤(3)的浓缩成稠膏,具体是煎煮完成后,合并煎液,滤过,浓缩成稠膏。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110990464.1A CN114177225A (zh) | 2021-08-26 | 2021-08-26 | 一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110990464.1A CN114177225A (zh) | 2021-08-26 | 2021-08-26 | 一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114177225A true CN114177225A (zh) | 2022-03-15 |
Family
ID=80601038
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110990464.1A Pending CN114177225A (zh) | 2021-08-26 | 2021-08-26 | 一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114177225A (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111450136A (zh) * | 2020-06-12 | 2020-07-28 | 广西医科大学 | 一种牡蛎葛根复合颗粒及其制备方法 |
-
2021
- 2021-08-26 CN CN202110990464.1A patent/CN114177225A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111450136A (zh) * | 2020-06-12 | 2020-07-28 | 广西医科大学 | 一种牡蛎葛根复合颗粒及其制备方法 |
Non-Patent Citations (2)
Title |
---|
林桂宇,等: "牡蛎葛根固体饮料对实验性高血脂症小鼠的血脂调节及肝脏保护作用研究", 《广西医科大学学报》 * |
梁春,等: "《高脂血症》", 30 September 2016, 第二军医大学出版社 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Fan et al. | Tangganjian decoction ameliorates type 2 diabetes mellitus and nonalcoholic fatty liver disease in rats by activating the IRS/PI3K/AKT signaling pathway | |
CN105031591B (zh) | 一种治疗慢性肾功能衰竭的中药组合物及其制备方法 | |
CN106924374B (zh) | 一种组合物及其制备方法与在制备降血糖和/或降血脂的产品中的应用 | |
CN108888670A (zh) | 一种治疗溃疡性结肠炎的结肠靶向胶囊剂及其制备工艺 | |
CN106177183A (zh) | 一种包含青钱柳叶、绿茶和桑叶的降血糖保健组合物 | |
Yin et al. | A proprietary herbal drug Young Yum Pill ameliorates chronic fatigue syndrome in mice | |
CN114177225A (zh) | 一种牡蛎葛根复方中药组合物在作为治疗/预防高脂血症药物方面的应用 | |
CN105079629A (zh) | 一种用于防治阿尔茨海默病的中药组合物及其制备方法和用途 | |
CN102106993B (zh) | 一种治疗脂肪肝的中药组合物及其制备方法 | |
CN110613792B (zh) | 一种具有降血糖作用的中药组合物及其制备方法和应用 | |
CN100467043C (zh) | 一种治疗骨质疏松症的中药及制备方法 | |
CN105288501A (zh) | 一种含有艾叶的治疗肥胖症的中药制剂 | |
JP2023505620A (ja) | 漢方薬組成物及びその製造方法並びに使用 | |
WO2010037255A1 (zh) | 一种人参绞股蓝复方制剂在制备调节血脂、血糖的药物中的用途 | |
CN104887766A (zh) | 一种治疗动脉粥样硬化的中药复方胶囊及制备方法 | |
CN117323371B (zh) | 一种治疗肥胖型多囊卵巢综合征的中药组合物及其制备方法 | |
CN109200250A (zh) | 一种治疗乳腺癌的中药组合物及其制备方法 | |
CN100560087C (zh) | 治疗恶性肿瘤的药物组合物及其制备方法 | |
CN115282201A (zh) | 防治糖尿病合并脂肪肝的中药配伍方组合物及其制备方法和应用 | |
CN105641633A (zh) | 一种中药制剂在制备治疗肥胖症的药物中的用途 | |
CN116570702B (zh) | 一种抗射血分数保留型心力衰竭的中药组合物及其应用 | |
CN116211990B (zh) | 一种治疗糖尿病突发性耳聋的中药组合物 | |
CN115779049B (zh) | 一种用于化疗致骨髓抑制的中药组合物及其制剂与应用 | |
CN102335362A (zh) | 一种治疗2型糖尿病胰岛素抵抗的中药 | |
CN105288498A (zh) | 一种制备含有艾叶的治疗肥胖症的中药制剂的方法 |
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 | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220315 |
|
RJ01 | Rejection of invention patent application after publication |