CN106214810A - 异喹啉生物碱的提取物 - Google Patents
异喹啉生物碱的提取物 Download PDFInfo
- Publication number
- CN106214810A CN106214810A CN201610824951.XA CN201610824951A CN106214810A CN 106214810 A CN106214810 A CN 106214810A CN 201610824951 A CN201610824951 A CN 201610824951A CN 106214810 A CN106214810 A CN 106214810A
- Authority
- CN
- China
- Prior art keywords
- phellodendrine
- extract
- isoquinoline alkaloid
- compositions
- magnocurarine
- 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
- 239000000284 extract Substances 0.000 title claims abstract description 64
- 229930013397 isoquinoline alkaloid Natural products 0.000 title claims abstract description 37
- JFJZZMVDLULRGK-URLMMPGGSA-O tubocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CCN3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 JFJZZMVDLULRGK-URLMMPGGSA-O 0.000 title claims abstract description 37
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 230000002265 prevention Effects 0.000 claims abstract description 3
- RBBVPNQTBKHOEQ-KKSFZXQISA-O Phellodendrine Chemical compound C1CC2=CC(OC)=C(O)C=C2[C@H]2[N@+]1(C)CC(C=C(C(=C1)O)OC)=C1C2 RBBVPNQTBKHOEQ-KKSFZXQISA-O 0.000 claims description 105
- CLWOXNLVWMXBRD-QGZVFWFLSA-O Magnocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=CC=21)O)OC)C1=CC=C(O)C=C1 CLWOXNLVWMXBRD-QGZVFWFLSA-O 0.000 claims description 52
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 38
- YLRXAIKMLINXQY-ZDUSSCGKSA-O (S)-magnoflorine Chemical compound C1=C(OC)C(O)=C2C3=C(O)C(OC)=CC=C3C[C@@H]3[N+](C)(C)CCC1=C23 YLRXAIKMLINXQY-ZDUSSCGKSA-O 0.000 claims description 26
- KYEAXNAYHSCLMT-CVVGWEDFSA-N Magnoflorine Natural products C[C@H]1OC=C2[C@@H]3[C@@H]1CN4CCc5c([nH]c6ccccc56)[C@@H]4[C@@H]3OC2=O KYEAXNAYHSCLMT-CVVGWEDFSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 24
- 102000004877 Insulin Human genes 0.000 claims description 19
- 108090001061 Insulin Proteins 0.000 claims description 19
- 229940125396 insulin Drugs 0.000 claims description 19
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 16
- 238000002347 injection Methods 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 235000013305 food Nutrition 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 208000004930 Fatty Liver Diseases 0.000 claims description 3
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 208000010706 fatty liver disease Diseases 0.000 claims description 3
- 230000036541 health Effects 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 claims description 3
- 206010018473 Glycosuria Diseases 0.000 claims description 2
- 230000008485 antagonism Effects 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 235000013376 functional food Nutrition 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 238000007639 printing Methods 0.000 claims description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 abstract description 15
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 15
- 208000033679 diabetic kidney disease Diseases 0.000 abstract description 15
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 abstract description 5
- 201000005577 familial hyperlipidemia Diseases 0.000 abstract description 3
- 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 40
- 239000008103 glucose Substances 0.000 description 40
- 210000004369 blood Anatomy 0.000 description 29
- 239000008280 blood Substances 0.000 description 29
- 238000000605 extraction Methods 0.000 description 25
- 239000007788 liquid Substances 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 239000011347 resin Substances 0.000 description 14
- 229920005989 resin Polymers 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 235000000346 sugar Nutrition 0.000 description 13
- 238000010828 elution Methods 0.000 description 12
- 239000012567 medical material Substances 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 229930013930 alkaloid Natural products 0.000 description 11
- 238000001819 mass spectrum Methods 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 10
- 238000011068 loading method Methods 0.000 description 10
- 239000003463 adsorbent Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 235000009200 high fat diet Nutrition 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- 206010022489 Insulin Resistance Diseases 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 6
- 230000037213 diet Effects 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 239000007791 liquid phase Substances 0.000 description 6
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 6
- 239000006199 nebulizer Substances 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 108010088751 Albumins Proteins 0.000 description 5
- 102000009027 Albumins Human genes 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 5
- 150000001720 carbohydrates Chemical class 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 229940109239 creatinine Drugs 0.000 description 5
- 238000003304 gavage Methods 0.000 description 5
- 230000003914 insulin secretion Effects 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000001179 sorption measurement Methods 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000003907 kidney function Effects 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000004445 quantitative analysis Methods 0.000 description 4
- 230000000630 rising effect Effects 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 3
- 108010082126 Alanine transaminase Proteins 0.000 description 3
- PTPHDVKWAYIFRX-UHFFFAOYSA-N Palmatine Natural products C1C2=C(OC)C(OC)=CC=C2C=C2N1CCC1=C2C=C(OC)C(OC)=C1 PTPHDVKWAYIFRX-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000003908 liver function Effects 0.000 description 3
- 208000030159 metabolic disease Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- QUCQEUCGKKTEBI-UHFFFAOYSA-N palmatine Chemical compound COC1=CC=C2C=C(C3=C(C=C(C(=C3)OC)OC)CC3)[N+]3=CC2=C1OC QUCQEUCGKKTEBI-UHFFFAOYSA-N 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 2
- FZEAFQGXLLXUFJ-UHFFFAOYSA-N 1-methylisoquinolin-6-ol Chemical compound OC1=CC=C2C(C)=NC=CC2=C1 FZEAFQGXLLXUFJ-UHFFFAOYSA-N 0.000 description 2
- 241001111317 Chondrodendron tomentosum Species 0.000 description 2
- 239000008709 Curare Substances 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 241001362856 Lepisorus miyoshianus Species 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- 241000282894 Sus scrofa domesticus Species 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000001518 anti-nephritic effect Effects 0.000 description 2
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 2
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 2
- 229940093265 berberine Drugs 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 230000009172 bursting Effects 0.000 description 2
- 230000023852 carbohydrate metabolic process Effects 0.000 description 2
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 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 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 208000016097 disease of metabolism Diseases 0.000 description 2
- 208000028208 end stage renal disease Diseases 0.000 description 2
- 201000000523 end stage renal failure Diseases 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical group C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 238000004451 qualitative analysis Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 241000551547 Dione <red algae> Species 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021118 Hypotonia 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
- MXTLAHSTUOXGQF-UHFFFAOYSA-O Jatrorrhizine Chemical compound COC1=CC=C2C=C3C(C=C(C(=C4)O)OC)=C4CC[N+]3=CC2=C1OC MXTLAHSTUOXGQF-UHFFFAOYSA-O 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 208000007379 Muscle Hypotonia Diseases 0.000 description 1
- 206010031253 Osteomyelitis acute Diseases 0.000 description 1
- 206010031256 Osteomyelitis chronic Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010036772 Proctalgia Diseases 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241001093501 Rutaceae Species 0.000 description 1
- 206010040840 Skin erosion Diseases 0.000 description 1
- 208000033809 Suppuration Diseases 0.000 description 1
- 235000009430 Thespesia populnea Nutrition 0.000 description 1
- 244000299492 Thespesia populnea Species 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000031971 Yin Deficiency Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 238000004134 energy conservation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000009207 exercise therapy Methods 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 208000017561 flaccidity Diseases 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 210000002601 glomerular mesangium Anatomy 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 235000021070 high sugar diet Nutrition 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000008720 membrane thickening Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 230000001047 pyretic effect Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 201000004647 tinea pedis Diseases 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- 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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/756—Phellodendron, e.g. corktree
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及异喹啉生物碱的提取物的医药用途,具体涉及预防或治疗糖尿病、高脂血症、非酒精性脂肪肝、糖尿病肾病。
Description
技术领域
本发明涉及天然药物领域,涉及异喹啉生物碱的提取物,具体涉及异喹啉生物碱的提取物的医药用途。
背景技术
糖尿病是一种由于胰岛素分泌缺陷及(或)其生物学作用障碍引起的以高血糖为特征的代谢疾病,是在遗传基础上,有环境因素参与的遗传易感性疾病,是一种慢性全身性代谢疾病,严重危害人类健康,积极开展糖尿病的防治工作已成为主要的社会公共卫生问题。
I型糖尿病的发病原因主要是由于胰岛素分泌绝对缺少,II型糖尿病是从胰岛素抵抗为主伴胰岛素相对不足到胰岛素分泌不足为主伴胰岛素抵抗的病理过程。目前公认II型糖尿病是一种在环境因素、生活方式的改变的作用下由多个基因分别或相互作用所导致的复杂遗传病,但是II型糖尿病的病因尚未完全阐明。
西医目前常采用饮食、运动疗法磺酰脲类、双胍类、噻唑烷二酮类、α-葡萄糖苷酶抑制剂、瑞格列奈、胰岛素等来治疗II型糖尿病,仅噻唑烷二酮类可改善胰岛素抵抗。病人在用西药治疗的同时,又不断地出现动脉硬化、冠心病和高血压等并发症,II型糖尿病的复杂机制及其导致的全身病变是西药治疗的薄弱环节。不论是磺酰脲类的促泌剂还是噻唑烷二酮类的增敏剂在实验和临床研究中都不具备明显的减肥功效,而肥胖是2型糖尿病乃至代谢综合征的重要病理基础。
II型糖尿病不仅是糖代谢紊乱疾病,还是脂肪代谢紊乱疾病。肥胖引起的II型糖尿病患者通常都有高糖和高脂饮食,并常伴有高脂血症。有研究表明提示血糖“正常”的肥胖患者己有β细胞分泌功能的异常。但是,大部分的肥胖者并不发展为糖尿病,说明机体的自身状况起重要作用。在同样的毒性作用下,易感人群很容易发展成II型糖尿病,而不敏感人群可能终身不发病,或者延迟发病。现代医学并不能够改变机体的易感性,但可以通过改变生活方式,减肥等手段来尽可能地减少早期的诱因,尽量的延长代偿期,从而延迟2型糖尿病的发生,甚至避免发病。
现代II型糖尿病的治疗观点已从已往的单纯控制血糖转为降糖、降脂、降压、改善胰岛素抵抗等多环节治疗。但是,对于II型糖尿病患者,药量需逐渐增加,投药种类也常由单一用药逐渐变为联合用药,这不可避免地要考虑药物代谢对肝肾的副作用。故从传统中药中寻找低毒、疗效肯定的天然药物来治疗是目前研糖尿病究热点之一。
卫生部制定颁布的《中药新药治疗消渴病(糖尿病)的临床研究指导原则》中所制定的分类标准是目前采用最广泛的分类方法,即阴虚热盛证、气阴两虚证、阴阳两虚证和血疲气滞证四型。
非酒精性脂肪肝是一种无过量饮酒史,由各种原因引起的肝细胞内脂肪堆积,以肝细胞脂肪变性和脂质蓄积为主要特征的临床病理综合征,也是一种临床常见病症。
糖尿病肾病(diabetic nephropathy,DN)是糖尿病最重要的并发症之一,我国的发病率亦呈上升趋势,目前已成为终末期肾病的第二位,仅次于肾小球肾炎,由于存在复杂的代谢紊乱,糖尿病发生肾脏损害,特别是一旦进入临床蛋白尿期,病情一般不可逆转,往往呈进行性发展直至终末期肾病,往往比其他肾脏疾病的治疗更加困难,是引起糖尿病患者死亡的主要原因之一,DN的发病机制和治疗药物的研制受到了医学界极大的重视。现代医学上多从饮食控制、血糖控制、降压、调整脂代谢等方面着手,或是采用透析、肾移植等治疗手段,尚无疗效确切的西药能阻止DN肾功能损害的进程。临床其主要诊断的特征为白蛋白排泄率,和白蛋白肌酐比值。
黄柏为我国常用的传统中药,始载于《神农本草经》,原名“檗木”,列为上品,其性味苦、寒,主归肾、膀胱经,具有清热燥湿,湾火除蒸,解毒疗疫之功效,用于湿热汚痢,黄疸尿赤,带下阴痒,热淋淫痛,脚气痿蹵,骨蒸劳热,盗汗,遗精,肿毒,湿疹。现代药理研究表明,黄柏具有抗菌、抗真菌、抗炎、抗肝炎、抗肾炎、抗溃病、抗氧化、抗痛风、降血压、降血糖、抗肿瘤、抗心力衰竭、抑制细胞免疫等作用。目前黄柏制剂在临床上已经广泛运用,如治疗鼻窦炎、急慢性脓耳、急慢性骨髓炎、慢性结肠炎、皮肤糜烂、脓拖性皮损、湿疫皮炎、溃窃性口腔炎、外痔肿痛、肛痛以及术后外洗、治疗软组织挫伤、消肿等病症。(《黄柏中黄柏碱的提取纯化工艺研究》,《西南交 通大学硕士研究生学位论文》,罗鸿,2012年)。
黄柏碱(Phellodendrine)是从芸香科植物黄柏(Phelhdendron chinensisSchneid.)、威氏黄柏的茎皮中提取分离出来的一种异喹啉生物碱,其具有降血压、抗肾炎、抑制细胞免疫反应、中枢神经抑制等作用。
黄柏碱的药理作用主要有:降压作用,主要表现为静注于猫和鼠和犬均可引起降压,并能增强肾上腺素和去甲肾上腺素的升压反应,抑制人工窒息及刺激迷走神经向中端的升压反应,抑制刺激节前纤维而起的猫瞬膜收缩。随剂量增大,降压作用强度及持续时间也增加;植物神经阻断作用,表现为黄柏碱对中枢神经有抑制作用,能抑制小鼠的自发活动和各种反射;肌肉松驰作用;对细胞免疫应答期的诱导期有抑制作用。
《黄柏中几种生物碱的分离、鉴定及促胰岛素分泌活性筛选》(《中国医药指南》,2011年3月,第9卷,第7期,第54-55页,周明伟、范明松、季宇斌、唐意红)记载了:从黄柏的生物碱部分分离得到3个化合物,分别为小檗碱、药根碱、黄柏碱。研究发现,在葡萄糖浓度为5.6mmol/L时,黄柏总碱中的3种生物碱对胰岛素的分泌均无明显的促进作用;而当葡萄糖浓度为16.7mmol/L时,小檗碱能够明显的促进细胞的胰岛素分泌。阳性药格列美脲在低糖浓度和高糖浓度时,都能够促进胰岛素分泌。
发明内容
异喹啉生物碱的提取物,其特征在于:含有如下组分。
黄柏碱 35-50%、
黄柏碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:含有如下组分。
木兰箭毒碱 1-4%、
黄柏碱 35-50%
木兰箭毒碱、黄柏碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:含有如下组分。
黄柏碱 35-50%、
木兰花碱 15-25%;
黄柏碱、木兰花碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:含有如下组分。
木兰箭毒碱 1-4%、
黄柏碱 35-50%、
木兰花碱 15-25%;
木兰箭毒碱、黄柏碱、木兰花碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:指纹图谱如说明书附图1所示。
异喹啉生物碱的提取物,其特征在于:含有如下组分。
黄柏碱 43.94%、
黄柏碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:含有如下组分。
木兰箭毒碱 2.68%、
黄柏碱 43.94%、
木兰箭毒碱、黄柏碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:含有如下组分。
黄柏碱 43.94%、
木兰花碱 22.99%;
黄柏碱、木兰花碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:含有如下组分。
木兰箭毒碱 2.68%、
黄柏碱 43.94%、
木兰花碱 22.99%;
木兰箭毒碱、黄柏碱、木兰花碱、其他成分的含量之和为100%。
异喹啉生物碱的提取物,其特征在于:从黄柏中提取。
本发明异喹啉生物碱的提取物,涉及黄柏生物碱的提取物。
异喹啉生物碱的提取物,其特征在于:用于制备对抗胰岛素抵抗的组合物。
异喹啉生物碱的提取物,其特征在于:用于制备治疗或预防非酒精性脂肪肝的组合物。
异喹啉生物碱的提取物,其特征在于:用于制备治疗或预防糖尿病肾病的组合物。
异喹啉生物碱的提取物,其特征为:药物、保健品、或功能性食品,赋形剂或载体为制药或食品领域中常用的赋形剂或载体,如稀释剂,崩解剂,润滑剂等。
异喹啉生物碱的提取物,其特征为通过口服或注射形式使用。
异喹啉生物碱的提取物,其特征为:用于制备治疗I、或II型糖尿病的组合物。
异喹啉生物碱的提取物的优选的制备方法
(1)黄柏总生物碱
配制NaCl溶液,调其PH为酸性;干燥黄柏药材用该溶液以料液浸泡提取1-5次,每次0.2-100h,合并提取液;
(2)黄柏碱的提取物
将合并提取液通过大孔吸附树脂柱层析吸附,吸附完毕后,先用水洗脱除杂;再用20-50%乙醇洗脱,收集洗脱液,减压浓缩得浸膏。
大孔吸附树脂:包括而不限于D301、D354、D203、D003..D201、D296、D113、HPD100型大孔吸附树脂。
异喹啉生物碱的提取物的优选的制备方法
(1)黄柏总生物碱
配制质量分数为1.0-10.0%的NaCl溶液,调其PH为1.0-5.0;干燥黄柏药材用该溶液以料液比1-5:8-100浸泡提取1-5次,每次1-100h,合并提取液;
(2)黄柏碱的提取物
将合并提取液通过HPD100型大孔吸附树脂柱层析吸附,吸附完毕后,先用水洗脱除杂;再用20-50%乙醇洗脱,收集洗脱液,减压浓缩得浸膏。
异喹啉生物碱的提取物的优选的制备方法
(1)黄柏总生物碱
配制质量分数为3.0%的NaCl溶液,调其PH为3.0;干燥黄柏药材用该溶液以料液比1:8浸泡提取2次,每次48h,合并提取液;
(2)黄柏碱的提取物
将合并提取液通过HPD100型大孔吸附树脂柱层析吸附,干燥的黄柏药材与大孔吸附树脂的质量比为1:5,上样速度控制在2.0ml/min,上样完毕后静止 吸附2.0h;吸附完毕后,先用3.0BV的水洗脱除杂;再用30%乙醇洗脱3.0BV,收集洗脱液,于50℃减压浓缩得浸膏。
黄柏碱的提取物的定性和定量分析
称取黄柏碱的提取物样品1.14mg,用甲醇溶解,配制成11.4μg/mL的溶液,离心取上清后进行分析。
1.液相条件
流动相0.1%甲酸水-甲醇
流速0.4ml/min
Post time:2min
进样量:1μL
2.质谱条件
Gas Tem:350℃
Sheath Gas Tem:350℃
Gas Flow:10L/min
Sheath Gas Flow:11L/min
Nebulizer:35V
VCap:3500V
Fragmentor:120V
Skimmer:65V
Octopole RFPeak:750V
CE:10-30V
一、定量分析Agilent 6460QQQ MS
1.Scan模式(摸条件)
1.1液相条件
流动相0.1%甲酸水-甲醇
流速0.4ml/min
Post time:2min
进样量:1μL
1.2QQQ-MS条件
Gas Tem:300℃
Sheath Gas Tem:300℃
Gas Flow:10L/min
Sheath Gas Flow:11L/min
Nebulizer:45V
Vcharging:500
2.MRM模式(正式定量)
2.1液相条件
流动相0.1%甲酸水-甲醇
流速0.4ml/min
Post time:2min
进样量:1μL
2.2QQQ-MS条件
Gas Tem:300℃
Sheath Gas Tem:300℃
Gas Flow:10L/min
Sheath Gas Flow:11L/min
Nebulizer:45V
标准曲线的配制:
取30μg/mL黄柏碱、7μg/ml木兰花碱和0.52μg/ml木兰箭毒碱做母液,通过稀释,配制成范围为0.12-12μg/ml(黄柏碱)、0.028-2.8μg/ml(木兰花碱)、0.52-52ng/ml(木兰箭毒碱)的系列溶液。取80μL浓度为11.4μg/mL的标准溶液,加入20μL浓度为5μg/mL的内标(巴马汀)溶液,混匀后进样。
样品处理:
取80μL浓度为11.4μg/mL的样品溶液,加入20μL浓度为5μg/mL的内标(巴马汀)溶液,混匀后进样。
处理数据后,通过DAS软件分析,得出三条标曲
黄柏碱 y=0.415+0.736x
木兰花碱 y=0.008+0.211x
木兰箭毒碱 y=0.001x
编号;化合物;峰面积百分比;含量
1;分子量为298,为3,4-Dihydro-1-[(4-hydroxyphenyl)methyl]-7-methoxy-2-methyl-8-isoquinolinol、3,4-Dihydro-1-[(4-hydroxyphenyl)methyl]-7-methoxy-2-methyl-6-isoquinolinol中的任意一种;5.92%;0.0459mg/mg
2;木兰箭毒碱;2.68%;0.995μg/mg
3;分子量为342,未知;1.17%;0.0908μg/mg
4;黄柏碱;43.94%;0.341mg/mg
5;木兰花碱;22.99%;0.163mg/mg
6;分子量为448,为N-Methylhigenamine-7-O-glucopyranoside;
7.45%;0.0578mg/mg
7;分子量为314;为莲心季铵碱;15.85%;0.123mg/mg
此编号1-7对应说明书附图1的编号。
基于上述发现,本发明现已完成。为了便于理解,需要特别指出的是,具体实施例和附图仅是为了说明,显然本领域的技术人员可以根据本文说明,对本发明进行各种修正或改变,这些修正和改变也将纳入本发明范围之内。
附图说明
图1:黄柏提取物PC Fr.B160615的总离子质谱图
图2:木兰箭毒碱质谱图
图3:黄柏碱质谱图
图4:木兰花碱质谱图
图5:黄柏提取物PC Fr.B160615MRM模式下的质谱图
图6:木兰箭毒碱在MRM模式下的质谱图
图7:黄柏碱在MRM模式下的质谱图
图8:木兰花碱在MRM模式下的质谱图
图9:巴马汀(内标)在MRM模式下的质谱图
附图的进一步解释:
在图1黄柏提取物PC Fr.B160615的总离子质谱图中:
1:未知 2:木兰箭毒碱 3:未知 4:黄柏碱 5:木兰花碱 6:未知 7:未知
在图5黄柏提取物PC Fr.B160615MRM模式下的质谱图
2:木兰箭毒碱 4:黄柏碱 5:木兰花碱 7:未知
具体实施方式
实施例1
为了研究黄柏碱对I型糖尿病血糖影响,本实验采用经典的I型糖尿病模型,使用C57BL小鼠随机分为3组,正常对照组(10只),STZ组(20只)。STZ组连续腹腔注射STZ(50mg/Kg)5天,两周后测定禁食血糖,血糖大于等于13.8mmol/L为造模成功。然后将STZ组随机分为STZ组和黄柏碱治疗组,每组10只,黄柏碱治疗组采用口服灌胃(15mg/kg)10周后,禁食4h后测定禁食血糖,具有显著的统计学差异。
动物的一般情况:
胰岛组织病理学检查:石蜡切片、HE染色,观察病理变化
表1.黄柏碱对STZ造模的I型糖尿病血糖的影响.
注:*P<0.05,**P<0.01,***P<0.001,与STZ组相比。
结果表明黄柏碱能够有效的降低STZ造成的I型糖尿病的血糖
表2.黄柏碱对STZ造模的小鼠胰岛数目的影响
注:*P<0.05,**P<0.01,***P<0.001,与STZ组相比。
随机选取胰腺病理切片9个视野进行统计。结果显示STZ造模后胰腺萎缩,组织结构坏死,通过黄柏碱治疗后胰岛组织形态结构恢复明显。注:标尺为20μm,放大倍数400倍。
实施例2
为了研究黄柏碱对II型糖尿病的影响,本实验采用经典的II型糖尿病模型,使用C57BL小鼠随机分为3组,正常对照组(10只),模型组(10只),黄柏碱治疗组(10只),其中模型组和黄柏碱治疗组采用高脂饮食(基础饲料加入20%猪油)造模8周,黄柏碱治疗组在高脂饮食同时采用口服灌胃(50mg/kg)方式给药,给药结束后测定禁食过夜测定、空腹血糖、葡萄糖耐量和 胰岛素耐量。实验数据进行方差分析,结果以x±s表示。结果显示,黄柏碱治疗效果明显,具有显著统计学差异。
实验结果:
表3.黄柏碱对高脂造模的II型糖尿病禁食血糖的影响
注:***P<0.001,与正常组相比;*P<0.05,***P<0.001,与高脂组相比
糖耐量试验是一种口服葡萄糖负荷试验,用以了解机体对进食葡萄糖后的血糖调节能力。通过糖耐量试验,可以早期发现糖代谢异常,是目前公认的诊断糖尿病的金标准,在血糖增高但尚未达到糖尿病诊断标准时,为明确是否患糖尿病,可以采用OGTT进行鉴别诊断。正常情况下,机体有一套维持血糖的机制,口服葡萄糖,血糖短暂升高后迅速恢复正常,即糖耐量正常,相应的口服糖耐量曲线线下面积较小,糖尿病患者糖的利用障碍,口服葡萄糖后血糖迅速升高,血糖下降速度较慢,即糖耐量减退相应的线下面积较大,该实验中糖耐量减退,
黄柏碱治疗组和正常组的糖耐量曲线均在模型组曲线下,相应的线下面积也均低于模型组,且具有统计意义。
糖耐量实验方法:小鼠禁食过夜,小鼠口服血糖2g/kg后分别在0,15,30,60,90,120min时,尾尖采血测定相应血糖,使用GraphPad Prism软件计算相应线下面积(AUC)
胰岛素耐受实验方法:小鼠禁食过夜,小鼠腹腔注射胰岛素0.75IU/kg后分别在0,30,60,90,120,150min时,尾尖采血测定相应血糖,使用GraphPad Prism软件计算相应线下面积(AUC)
糖耐量原始数据如下:
表4.正常组小鼠糖耐量原始数据
表5.高脂组小鼠糖耐量原始数及相应线下面积
表6.黄柏碱治疗高脂饮食小鼠糖耐量原始数及线下面积
注:control为正常饮食组,HFD为高脂饮食组,HFD+Phellodendrine组为高脂
表7.黄柏碱对口服糖耐量线下面积数据分析
胰岛素耐量试验是反映机体对胰岛素敏感性的实验,II型糖尿病的主要特征为胰岛素抵抗,对胰岛素敏感性降低,即注射相同胰岛素相同时间内血糖高于正常机体,高脂造模后对胰岛素敏感性降低,注射相同量的胰岛素后各个点的血糖值均高于正常组,其相应的线下面积也高于正常组,给予黄柏碱治疗后各个时间点的血糖数值低于模型组,相应线下面积低于高脂诱导的模型组。结果表明黄柏碱能够有效的增加胰岛素敏感性改善糖尿病。
表8.正常组小鼠糖胰岛素耐量原始数据
表9.高脂组小鼠糖胰岛素耐量原始数据
表10.黄柏碱治疗组小鼠糖胰岛素耐量原始数据
表11.黄柏碱对II型糖尿病小鼠糖胰岛素耐量线下统计分析
注:*P<0.05,**P<0.01,***P<0.001,与高脂组比较
可见:与正常组相比,模型组小鼠空腹血糖值显著升高,说明II型糖尿病模型造模成功。同时,与模型组相比,黄柏碱有显著的降低空腹血糖的作用和增加葡萄糖耐受、增强胰岛素敏感性。
实施例3
黄柏碱对高脂血症和非酒精性脂肪肝的治疗作用,
1、实验动物及方法:
C57BL小鼠,SPF级,雄性,体重(20±2)g,随机分成两组,第一组12只,为正常组,给与正常饲料,其余小鼠(44只)分为第二组,给与高脂饲料(基础饲料加入20%猪油,1.25%胆固醇,0.5%的胆酸钠)自由摄食、饮水。连续喂养8周后,从正常对照组和脂肪肝模型组分别处死4只小鼠,比较两组小鼠的血清和肝脏生化指标,以及肝脏组织病理切片,判断非酒精性脂肪肝模型小鼠是否建立成功。
将造模成功小鼠32只随机分为4组,分别为正常对照组(8只),模型组(8只),黄柏碱治疗组(8只),阳性对照组(洛伐他汀组8只),连续灌胃给药8周。给药期间,除正常对照组标准饲料饲养外,其余各组继续给予高脂饮食,直到实验结束。黄柏碱治疗组在高脂饮食同时采用口服灌胃(50mg/kg)方式给药,阳性对照组在高脂饮食同时采用口服灌胃洛伐他汀(60mg/kg)方式 给药)
2、观察指标:
a动物的一般情况
实验动物在SPF动物房中饲养,12h光照12h黑夜,自由饮食饮水,实验期间动物状态正常。
b肝功能相关指标:血清ALT、AST,
c血脂相关指标:TC、TG、HDL、LDL
d病理学检查:HE染色
3、实验结果:
结果表明:黄柏碱均可明显降低血浆中的总胆固醇(TC)和甘油三酯(TG),升高高密度脂蛋白(HDL),降低低密度脂蛋白(LDL),降低血浆中天门冬氨酸转氨酶(AST),丙氨酸转氨酶(ALT),病理切片结果显示有效缓解高脂饲料引起的非酒精性脂肪肝变性,改善因脂肪变性而导致的肝功能损害。
给药结束后测定小鼠、血脂水平。实验数据进行方差分析,结果以x±s表示。结果显示,黄柏碱对降低高脂效果明显,具有显著统计学差异。
表12.各组小鼠血脂指标的变化
表13各组小鼠肝功能相关指标的变化
实施例4
为了研究黄柏碱对糖尿病肾病血糖影响,使用C57BL小鼠随机分为3组,正常对照组(10只),STZ组(20只)。STZ组连续腹腔注射STZ(50mg/Kg)5天,两周后测定禁食血糖,血糖大于等于13.8mM为糖尿病造模成功。然后将STZ组随机分为STZ组和黄柏碱治疗组,STZ组仅正常饲养,黄柏碱治疗组采用口服灌胃(15mg/kg),12周后,将小鼠放入小鼠代谢笼中,自由饮食饮水,将尿液用于分析,所测指标均为临床上糖尿病肾病的检测的经典指标,如表14-16所示STZ组相比空白对照组,显著升高均在10倍以上,说明糖尿病小鼠肾功能出现严重损伤,STZ组相比正常组器官损伤明显。综合以上表可以得出糖尿病肾病造模成功。
表14.结果表明黄柏碱能够有效的降低STZ造成的血糖升高,逆转由糖尿病肾病引起的尿量增加(表15),有效的降低糖尿病肾病引起的24h蛋白排泄率升高(表16)。临床上常用尿液中白蛋白和肌酐的比值评估肾功能,黄柏碱的有效的降低糖尿肾病引起的白蛋白和肌酐的比值升高(表17)。尿量、24h蛋白排泄率白蛋白和肌酐的比值的结果表明黄柏碱治疗很好的改善了肾功能。
为了更进一步的评估肾脏器官性损伤的改变,本发明对肾脏进行PAS染色和HE染色。黄柏碱能够有效的修复糖尿病肾病的器官性损伤逆转,STZ组肾小球系膜区增宽,基质增加,肾小球基膜增厚,肾小管基膜增厚及分裂,呈现出极为典型的糖尿病肾病特征,显示造模良好,而黄柏碱在一定程度上修复,系膜区相对缩小,改善了基质增生以及肾小管基膜增厚,说明治疗作用明显效果显著。
表14.黄柏碱对STZ造模的糖尿病肾病的血糖的影响(单位:mM).
注:*P<0.05,**P<0.01,***P<0.001,与STZ组相比。
表15.黄柏碱对STZ造模的糖尿病肾病的尿量的影响(单位:g).
表16.黄柏碱对STZ造模的糖尿病肾病的UAE(24h尿白蛋白排泄率,单位:μg)的影响.
表17.黄柏碱对STZ造模的糖尿病肾病的UACR(μg尿白蛋白/mg肌酐比值)的影响.
注:*P<0.05,**P<0.01,***P<0.001,与STZ组相比。
实施例5
黄柏碱的总提取物的制剂
黄柏碱的总提取物片剂
黄柏碱的总提取物10mg,淀粉88g,硬脂酸镁3g
制备工艺:取黄柏碱的总提取物过100目筛,加淀粉、硬脂酸镁混合均匀,制成颗粒,干燥,压片,即得。
黄柏碱的总提取物胶囊
黄柏碱的总提取物10mg,淀粉88g,硬脂酸镁3g
制备工艺:取黄柏碱的总提取物过100目筛,加淀粉、硬脂酸镁混合均匀,制成颗粒,干燥,装胶囊,即得。
黄柏碱的总提取物注射液
黄柏碱的总提取物47mg,注射用氯化钠7mg
制备工艺:取黄柏碱的总提取物过100目筛,加1.9mL注射用水溶解,加入注射用氯化钠至等渗,调节pH值至7~7.1,滤过,冷藏24小时,加注射用水至规定量,滤过,灌封,灭菌,即得。
实施例7
(1)总生物碱的提取
配制质量分数为3.0%的NaCl溶液,调其PH为3.0;干燥黄柏药材用该溶液以料液比1:8浸泡提取2次,每次48h,合并提取液;
(2)黄柏碱的总提取物
将合并提取液通过HPD100型大孔吸附树脂柱层析吸附,干燥的黄柏药材与大孔吸附树脂的质量比为1:5,上样速度控制在2.0ml/min,上样完毕后静止吸附2.0h;吸附完毕后,先用3.0BV的水洗脱除杂;再用30%乙醇洗脱3.0BV,收集洗脱液,于50□减压浓缩得浸膏;
实施例8
(1)总生物碱的提取
配制质量分数为3.0%的NaCl溶液,调其PH为3.0;干燥黄柏药材用该溶液以料液比1:8浸泡提取2次,每次48h,合并提取液;
(2)黄柏碱的总提取物
将合并提取液通过D101型大孔吸附树脂柱层析吸附,干燥的黄柏药材与大孔吸附树脂的质量比为1:5,上样速度控制在2.0ml/min,上样完毕后静止吸附2.0h;吸附完毕后,先用3.0BV的水洗脱除杂;再用30%乙醇洗脱3.0 BV,收集洗脱液,于50℃减压浓缩得浸膏。减压、真空干燥。
实施例9
(1)总生物碱的提取
配制质量分数为3.0%的NaCl溶液,调其PH为3.0;干燥黄柏药材用该溶液以料液比1:8浸泡提取2次,每次48h,合并提取液;
(2)黄柏碱的总提取物
将合并提取液通过D203型大孔吸附树脂柱层析吸附,干燥的黄柏药材与大孔吸附树脂的质量比为1:5,上样速度控制在2.0ml/min,上样完毕后静止吸附2.0h;吸附完毕后,先用3.0BV的水洗脱除杂;再用30%乙醇洗脱3.0BV,收集洗脱液,于50℃减压浓缩得浸膏。减压、真空干燥。
实施例10
(1)总生物碱的提取
配制质量分数为3.0%的NaCl溶液,调其PH为3.0;干燥黄柏药材用该溶液以料液比1:10浸泡提取2次,每次48h,合并提取液;
(2)黄柏碱的总提取物
将合并提取液通过D101型大孔吸附树脂柱层析吸附,干燥的黄柏药材与大孔吸附树脂的质量比为1:5,上样速度控制在2.0ml/min,上样完毕后静止吸附2.0h;吸附完毕后,先用3.0BV的水洗脱除杂;再用30%乙醇洗脱3.0BV,收集洗脱液,于50℃减压浓缩得浸膏。减压、真空干燥。
实施例11
黄柏碱的提取物的定性和定量分析
称取实施例7的样品1.14mg,用甲醇溶解,配制成11.4μg/mL的溶液,离心取上清后进行分析。
液相条件
流动相0.1%甲酸水-甲醇
流速0.4ml/min
Post time:2min
进样量:1μL
质谱条件
Gas Tem:350℃
Sheath Gas Tem:350℃
Gas Flow:10L/min
Sheath Gas Flow:11L/min
Nebulizer:35V
VCap:3500V
Fragmentor:120V
Skimmer:65V
Octopole RFPeak:750V
CE:10-30V
二、定量分析Agilent 6460QQQ MS
Scan模式(摸条件)
液相条件
流动相0.1%甲酸水-甲醇
流速0.4ml/min
Post time:2min
进样量:1μL
QQQ-MS条件
Gas Tem:300℃
Sheath Gas Tem:300℃
Gas Flow:10L/min
Sheath Gas Flow:11L/min
Nebulizer:45V
Vcharging:500
MRM模式(正式定量)
液相条件
流动相0.1%甲酸水-甲醇
流速0.4ml/min
Post time:2min
进样量:1μL
QQQ-MS条件
Gas Tem:300℃
Sheath Gas Tem:300℃
Gas Flow:10L/min
Sheath Gas Flow:11L/min
Nebulizer:45V
标准曲线的配制:
取30μg/mL黄柏碱、7μg/ml木兰花碱和0.52μg/ml木兰箭毒碱做母液,通过稀释,配制成范围为0.12-12μg/ml(黄柏碱)、0.028-2.8μg/ml(木兰花碱)、0.52-52ng/ml(木兰箭毒碱)的系列溶液。取80μL浓度为11.4μg/mL的标准溶液,加入20μL浓度为5μg/mL的内标(巴马汀)溶液,混匀后进样。
样品处理:
取80μL浓度为11.4μg/mL的样品溶液,加入20μL浓度为5μg/mL的内标
(巴马汀)溶液,混匀后进样。
处理数据后,通过DAS软件分析,得出三条标曲
黄柏碱 y=0.415+0.736x
木兰花碱 y=0.008+0.211x
木兰箭毒碱 y=0.001x
编号;化合物;峰面积百分比;含量
1;分子量为298,为3,4-Dihydro-1-[(4-hydroxyphenyl)methyl]-7-methoxy-2-methyl-8-isoquinolinol、3,4-Dihydro-1-[(4-hydroxyphenyl)methyl]-7-methoxy-2-methyl-6-isoquinolinol中的任意一种;5.92%;0.0459mg/mg
2;木兰箭毒碱;2.68%;0.995μg/mg
3;分子量为342,未知;1.17%;0.0908μg/mg
4;黄柏碱;43.94%;0.341mg/mg
5;木兰花碱;22.99%;0.163mg/mg
6;分子量为448,为N-Methylhigenamine-7-O-glucopyranoside;
7.45%;0.0578mg/mg
7;分子量为314;为莲心季铵碱;15.85%;0.123mg/mg
此编号对应说明书附图1的编号。
Claims (10)
1.异喹啉生物碱的提取物,其特征在于:含有如下组分中的任意一项
黄柏碱 35-50%、
黄柏碱、其他成分的含量之和为100%;或;
木兰箭毒碱 1-4%、
黄柏碱 35-50%、
木兰箭毒碱、黄柏碱、其他成分的含量之和为100%;或;
黄柏碱 35-50%
木兰花碱 15-25%;
黄柏碱、木兰花碱、其他成分的含量之和为100%;或;
木兰箭毒碱 1-4%,
黄柏碱 35-50%,
木兰花碱 15-25%,
木兰箭毒碱、黄柏碱、木兰花碱、其他成分的含量之和为100%。
2.根据权利要求1的异喹啉生物碱的提取物,其特征在于:含有如下组分:
黄柏碱 43.94%、
黄柏碱、其他成分的含量之和为100%;或;
木兰箭毒碱 2.68%、
黄柏碱 43.94%、
木兰箭毒碱、黄柏碱、其他成分的含量之和为100%;或;
异喹啉生物碱的提取物,其特征在于:含有如下组分。
黄柏碱 43.94%、
木兰花碱 22.99%、
黄柏碱、木兰花碱、其他成分的含量之和为100%;或;
木兰箭毒碱 2.68%、
黄柏碱 43.94%、
木兰花碱 22.99%、
木兰箭毒碱、黄柏碱、木兰花碱、其他成分的含量之和为100%。
3.根据权利要求1-2的异喹啉生物碱的提取物,其特征在于:从黄柏中提取。
4.根据权利要求1-2的异喹啉生物碱的提取物,其特征在于:用于制备对抗胰岛素抵抗的组合物。
5.根据权利要求1-2的异喹啉生物碱的提取物,其特征在于:用于制备治疗或预防非酒精性脂肪肝的组合物。
6.根据权利要求1-2的异喹啉生物碱的提取物,其特征在于:用于制备治疗或预防糖尿病肾病的组合物。
7.根据权利要求1-2的异喹啉生物碱的提取物,其特征为:药物、保健品、或功能性食品,赋形剂;载体为制药或食品领域中常用的赋形剂或载体,如稀释剂,崩解剂,润滑剂。
8.根据权利要求1-2的异喹啉生物碱的提取物,其特征为通过口服或注射形式使用。
9.根据权利要求1-2的异喹啉生物碱的提取物,其特征为:I、或II型糖尿病。
10.异喹啉生物碱的提取物,其特征在于:指纹图谱如说明书附图1所示。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610824951.XA CN106214810A (zh) | 2016-09-14 | 2016-09-14 | 异喹啉生物碱的提取物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610824951.XA CN106214810A (zh) | 2016-09-14 | 2016-09-14 | 异喹啉生物碱的提取物 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106214810A true CN106214810A (zh) | 2016-12-14 |
Family
ID=58075637
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610824951.XA Pending CN106214810A (zh) | 2016-09-14 | 2016-09-14 | 异喹啉生物碱的提取物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106214810A (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101798304A (zh) * | 2009-12-13 | 2010-08-11 | 成都普思生物科技有限公司 | 一种黄柏碱单体的分离纯化方法 |
CN102107006A (zh) * | 2009-12-25 | 2011-06-29 | 奇复康药物研发(苏州)有限公司 | 用于治疗糖尿病的偶联药物及其医药用途 |
-
2016
- 2016-09-14 CN CN201610824951.XA patent/CN106214810A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101798304A (zh) * | 2009-12-13 | 2010-08-11 | 成都普思生物科技有限公司 | 一种黄柏碱单体的分离纯化方法 |
CN102107006A (zh) * | 2009-12-25 | 2011-06-29 | 奇复康药物研发(苏州)有限公司 | 用于治疗糖尿病的偶联药物及其医药用途 |
Non-Patent Citations (2)
Title |
---|
KATARZYNA HOMA ET AL.: "False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome — is it the reason for the low number of reported cases of this abnormality?", 《ENDOKRYNOLOGIA POLSKA》 * |
石景森: "《脂肪肝防治专家谈》", 30 April 2015, 人民军医出版社 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103417749B (zh) | 一种紫花地丁提取物的制备方法及其在降糖药物中的应用 | |
CN107441078A (zh) | 一种治疗糖尿病的药物组合物及其制备方法和用途 | |
Wang et al. | Effect of ethanol extract of Rhodiola rosea on the early nephropathy in type 2 diabetic rats | |
Balwan et al. | Burden of diabetes and role of medicinal plants in its treatment | |
CN107163157B (zh) | 五味子酸性多糖及其制备方法和应用 | |
CA3022247C (en) | Composition for treating diabetic disease | |
Wang et al. | Hypoglycemic activity of CPU2206: A novel peptide from sika (Cervus nippon Temminck) antler | |
CN106214810A (zh) | 异喹啉生物碱的提取物 | |
CN104784192B (zh) | 蚌肉寡糖在制备降血糖药物中的应用及其制备方法 | |
CN103432207B (zh) | 一种连翘提取物木脂素的制备方法及其在降糖药物中的应用 | |
CN110314160A (zh) | 小檗胺在制备预防和治疗糖尿病肾病药物中的应用 | |
CN104042928B (zh) | 一种治疗糖尿病的药物组合物及其制备方法和用途 | |
CN102293274B (zh) | 一种防治糖耐量异常的粗茶组合物 | |
CN101816698A (zh) | 用于预防和治疗代谢紊乱综合症的组合物 | |
CN101138581A (zh) | 治疗泌尿系感染的中药制剂及其制备方法 | |
Ekhaise et al. | Evaluation of the methanolic extract of mistletoe (Tapinanthus Bangwensis) leaves grown on orange Trees for the phytochemical properties and its physiological effects on streptozotocin induced diabetes mellitus in laboratory animals | |
CN106138049A (zh) | 异喹啉生物碱防治高血脂症和非酒精性脂肪肝的用途 | |
CN106138046A (zh) | 一种异喹啉生物碱的预防或治疗糖尿病肾病的用途 | |
BHATTACHARJEE | DIABETIC NEPHROPATHY AMONG TYPE2 DIABETES MELLITUS INDIVIDUALS | |
CN102210725B (zh) | 田基黄总黄酮用于制备治疗肝纤维化的药物的用途 | |
CN105663626A (zh) | 一种知母有效部位及其制备方法和应用 | |
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 | |
Royani et al. | Comparison of the reduction in blood glucose levels of mice (mus musculus) given boiled water from ginger (zingiber officinale) with metformin | |
CN106138048A (zh) | 一种异喹啉生物碱的盐的降糖降脂保肝的用途 | |
CN105998031A (zh) | 榼藤子酸的应用及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161214 |
|
WD01 | Invention patent application deemed withdrawn after publication |