CN1325509C - 西洋参果总皂苷提取物在制备药物中的用途 - Google Patents
西洋参果总皂苷提取物在制备药物中的用途 Download PDFInfo
- Publication number
- CN1325509C CN1325509C CN 03127613 CN03127613A CN1325509C CN 1325509 C CN1325509 C CN 1325509C CN 03127613 CN03127613 CN 03127613 CN 03127613 A CN03127613 A CN 03127613A CN 1325509 C CN1325509 C CN 1325509C
- Authority
- CN
- China
- Prior art keywords
- group
- panacis quinquefolii
- total saponins
- fructus panacis
- fructus
- 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.)
- Expired - Fee Related
Links
- 229930182490 saponin Natural products 0.000 title claims abstract description 87
- 150000007949 saponins Chemical class 0.000 title claims abstract description 87
- 239000000284 extract Substances 0.000 title claims abstract description 30
- 239000001397 quillaja saponaria molina bark Substances 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title abstract description 12
- 240000005373 Panax quinquefolius Species 0.000 title abstract description 9
- 235000003140 Panax quinquefolius Nutrition 0.000 title abstract description 8
- 235000013399 edible fruits Nutrition 0.000 title abstract description 8
- 238000007670 refining Methods 0.000 title abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 50
- 208000031225 myocardial ischemia Diseases 0.000 claims abstract description 22
- 206010003119 arrhythmia Diseases 0.000 claims abstract description 10
- 230000006793 arrhythmia Effects 0.000 claims abstract description 10
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims description 10
- 235000017709 saponins Nutrition 0.000 abstract description 85
- 238000000605 extraction Methods 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 9
- 239000011347 resin Substances 0.000 abstract description 7
- 229920005989 resin Polymers 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000000274 adsorptive effect Effects 0.000 abstract 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 44
- 239000011780 sodium chloride Substances 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 210000004369 blood Anatomy 0.000 description 27
- 239000008280 blood Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 206010012601 diabetes mellitus Diseases 0.000 description 17
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 16
- 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 13
- 239000008103 glucose Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 230000007423 decrease Effects 0.000 description 11
- 210000002216 heart Anatomy 0.000 description 11
- 208000010125 myocardial infarction Diseases 0.000 description 11
- 239000006187 pill Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 241000282472 Canis lupus familiaris Species 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 230000002107 myocardial effect Effects 0.000 description 8
- 210000004165 myocardium Anatomy 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 230000000747 cardiac effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 241000700157 Rattus norvegicus Species 0.000 description 6
- 239000003463 adsorbent Substances 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 239000012266 salt solution Substances 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 229960001722 verapamil Drugs 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 102000004420 Creatine Kinase Human genes 0.000 description 3
- 108010042126 Creatine kinase Proteins 0.000 description 3
- 206010061216 Infarction Diseases 0.000 description 3
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 3
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- -1 iginates Species 0.000 description 3
- 230000007574 infarction Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- ZGZLYKUHYXFIIO-UHFFFAOYSA-N 5-nitro-2h-tetrazole Chemical compound [O-][N+](=O)C=1N=NNN=1 ZGZLYKUHYXFIIO-UHFFFAOYSA-N 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 206010000891 acute myocardial infarction Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000001435 haemodynamic effect Effects 0.000 description 2
- 229940090044 injection Drugs 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 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 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 230000036284 oxygen consumption Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 210000003516 pericardium Anatomy 0.000 description 2
- 230000036581 peripheral resistance Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229940095696 soap product Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- PSOUXXNNRFNUAY-UHFFFAOYSA-N (24S)-Pseudoginsenoside RT4 Natural products O1C(C(C)(O)C)CCC1(C)C1C(C(O)CC2C3(CC(C4C(C)(C)C(O)CCC42C)OC2C(C(O)C(O)C(CO)O2)O)C)C3(C)CC1 PSOUXXNNRFNUAY-UHFFFAOYSA-N 0.000 description 1
- JBGYSAVRIDZNKA-NKECSCAMSA-N (2S,3R,4R,5R,6S)-2-[(2R,3R,4S,5S,6R)-2-[[(3S,5R,6S,8R,9R,10R,12R,13R,14R,17S)-3,12-dihydroxy-17-[(2S,5R)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-6-yl]oxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]oxy-6-methyloxane-3,4,5-triol Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@@]3(C)O[C@H](CC3)C(C)(C)O)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O JBGYSAVRIDZNKA-NKECSCAMSA-N 0.000 description 1
- PSOUXXNNRFNUAY-BLSITOCHSA-N (3r,4s,5s,6r)-2-[[(3s,5r,6s,8r,9r,10r,12r,13r,14r,17s)-3,12-dihydroxy-17-[(2s,5r)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-6-yl]oxy]-6-(hydroxymethyl)oxane- Chemical compound O1[C@@H](C(C)(O)C)CC[C@@]1(C)[C@@H]1[C@@H]([C@H](O)C[C@H]2[C@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@@]42C)OC2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)[C@@]3(C)CC1 PSOUXXNNRFNUAY-BLSITOCHSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 244000267222 Brasenia schreberi Species 0.000 description 1
- 235000006506 Brasenia schreberi Nutrition 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 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
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 241000233855 Orchidaceae Species 0.000 description 1
- 241000208343 Panax Species 0.000 description 1
- 101100329392 Phytophthora infestans (strain T30-4) CRE2 gene Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 101100478272 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SPT6 gene Proteins 0.000 description 1
- 241000594182 Sarcophaga sigma Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- PZZYQPZGQPZBDN-UHFFFAOYSA-N aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940036811 bone meal Drugs 0.000 description 1
- 239000002374 bone meal Substances 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 208000015606 cardiovascular system disease Diseases 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- KVMXBSSOCCPAOR-UHFFFAOYSA-N ginsenoside ra1 Chemical compound C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC(C(C1O)O)OCC1OC1OCC(O)C(O)C1O KVMXBSSOCCPAOR-UHFFFAOYSA-N 0.000 description 1
- YLOTVUIQEWTDME-UHFFFAOYSA-N ginsenoside-Ra1 Natural products CC(=CCCC(C)(OC1OC(COC2OCC(OC3OCC(O)C(O)C3O)C(O)C2O)C(O)C(O)C1O)C4CCC5(C)C4C(O)CC6C7(C)CCC(OC8C(O)C(O)C(CO)OC8OC9OC(CO)C(O)C(O)C9O)C(C)(C)C7CCC56C)C YLOTVUIQEWTDME-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000005622 photoelectricity Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- JBGYSAVRIDZNKA-UHFFFAOYSA-N pseudo-ginsenoside-F11 Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C3C(C)(C)C(O)CCC3(C)C3C(C4(CCC(C4C(O)C3)C3(C)OC(CC3)C(C)(C)O)C)(C)C2)OC(CO)C(O)C1O JBGYSAVRIDZNKA-UHFFFAOYSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 150000008130 triterpenoid saponins Chemical class 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 229940020839 verapamil injection Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 235000015099 wheat brans Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Steroid Compounds (AREA)
Abstract
本发明涉及西洋参果总皂苷提取物在制备药物中的用途,属于从西洋参果肉有效成分得到西洋参果总皂苷提取物的药物用途领域。本发明目的在于西洋参果总皂苷提取物在制备治疗冠心病、心肌缺血及心律不齐和II型糖尿病的药物中的应用。用西洋参果总皂苷制备的治疗冠心病、心肌缺血、心律不齐、糖尿病药物,其优点是疗效好、无毒副作用、价格低廉等。
Description
技术领域
本发明涉及通过提取西洋参果肉有效成分得到西洋参果总皂苷提取物,其制备方法及含有这些提取物的药物组合物。
背景技术
西洋参果是西洋参成熟的果实。西洋参(panax quinquefolium L.)又称花旗参、美国人参、广东人参等,为五加科人参属植物,原产于美国、加拿大。西洋参味甘、微苦、性凉,能补脾降火、生津滋阴、除烦倦,虚而有火者相宜。我国自1975年以来,在华北、东北等地对西洋参进行了大面积栽培,并获得成功。根据资料记载西洋参有单茎、双茎和多茎之分,3-4年生的每一茎上可结10-30个果实,产量较高。
西洋参果总皂苷PQFS的提取、分离设计以及在药物方面的用途的理论基础为:本课题组经过多年对西洋参果化学成分及其生物活性的研究结果。利用先进的提取、分离及鉴定手段,从西洋参果中分离并鉴定了26个化合物,其中23个三萜皂苷,包括4个新发现的化合物,分别命名为西洋参皂苷-F1、-F2、-F3和-F4,其它为人参皂苷-Ra1、-Ra2、-Rb1、-Rb2、-Rb3、-Rc、-Rd、-Re、-Rg1、-Rg2、-Rg3(R、S)、-Rh1、-Rh2、伪人参皂苷-F11和RT5;一个新三糖及2个已知化合物。同时对其总皂苷的提取、精制方法进行了大量的研究,获得了具备生产量的西洋参果总皂苷提取物。经过对西洋参果总皂苷的药理活性研究表明,具有较强的治疗冠心病、心肌缺血及心律不齐和治II型糖尿病的生物功能。
发明内容
本发明提供一种西洋参果总皂苷提取物,在制备治疗冠心病、心肌缺血及心律不齐和II型糖尿病的药物中的应用。本发明涉及的西洋参果总皂苷提取物,其特征为浅黄色至褐色,粉末状,味苦,紫外光谱(甲醇)在203nm处有最大吸收峰,HPLC光谱显示出5个以上的峰,该西洋参果总皂苷提取物的含量占西洋参果肉干重的15%-20%。
本发明还涉及制备上述提取物的方法,它包括如下步骤:
(1)取西洋参果肉一定量,加3倍量的水在常温下,机械搅拌,100rpm,提取2-3次,每次提取1-3小时;
(2)将各次水煮所得的溶液合并,滤过,滤液备用;
(3)将上述滤液过大孔吸附树脂,然后用10%-20%乙醇洗涤,至接近无色,弃取洗液,继以50%-95%乙醇洗脱,收集该次洗脱液;
(4)将该洗脱液回收乙醇后,浓缩,干燥,得西洋参果总皂苷提取物。
本发明还涉及含有西洋参果总皂苷提取物作为活性成分的药物组合物,具体地讲,本发明涉及含有该提取物的用于治疗冠心病、心肌缺血及心律不齐II型糖尿病的药物组合物。本发明应用在制备治疗冠心病、心肌缺血及心律不齐和II型糖尿病的药物中。
本发明的产品或提取物可以通过适宜的方式配成片剂、软或硬明胶囊、用于制备与其溶解度相适应的即用溶液或液体的颗粒状粉末以及注射液。本发明西洋参果总皂苷提取物的剂量在30mg-400mg的范围内,可以每日给药一次或多次,优选200mg,每日给药2次,适宜的给药剂型是口服型。
本发明的特点及有益的效果是:西洋参果总皂苷提取物作为新的药用有效部位在治疗心血管疾病和糖尿病的药物组合中,作用明显,毒副作用小,治愈率高;西洋参果资源丰富,本发明采用的制备工艺方法,简单易行,适合工业化生产,总皂苷的收率高,具有广阔的应用前景。
本发明中提取、精制西洋参果总皂苷的具体方法是:
a.提取:以五加科人参属成熟的西洋参果为原料,经过除籽后,收集果肉、果汁为实验原料,采用最廉价经济的水作为提取溶剂,因为水具备了对西洋参果总皂苷的溶解度较大,沸点较高,安全又无环境污染,易回收等优点。
上述提取过程在常温下进行、采用机械搅拌方式,100γpm,加快提取,将一定量的西洋参果或汁用3倍量的水,分别提取3次,滤过,合并提取液,减压浓缩,0.07Mpa,至流膏状,比重1.11-1.21,得西洋参果总皂苷粗产品,低温保存。
b.精制:取西洋参果总皂苷粗品一定量,用水5倍的水稀释,稀释液上大孔吸附树脂D101,首先用水洗脱至无色,然后用10%-20%乙醇洗脱至无色,最后用70%-85%乙醇洗脱,收集最后洗脱液,回收洗脱剂得西洋参果总皂苷,产率10%-20%。纯度含西洋参果总皂苷55%-65%。
本发明的提取、精制方法的优点是一西洋参果为原料,在常温压下,以水为溶剂进行提取西洋参果总皂苷粗产品;进而以大孔吸附树脂进行精制,方法简单,不需要其他有毒的有机溶剂,收率高,达到了药物生产的纯度。
西洋参果总皂苷具有较好的治疗心血管疾病、II型糖尿病的药理活性,II型糖尿病中医称之为消渴症,属于气阴两虚型,因而西洋参果总皂苷可用于制备药物,特别适用于治疗冠心病、心肌缺血、心律不齐;治疗糖尿病等疾病。
为了用西洋参果总皂苷制备药品,将其制成一种形式的药物制剂,该制剂除活性成分外,还有固体或液体的赋形剂。给药方法及给药的剂型通常是这样的,内服情况下,其可以任何常规形式给药,如散剂、粒剂、片剂、胶囊剂、丸剂等,溶液剂如悬浮剂、糖浆等,口腔含片、舌下含片等。在这里使用的固体或液体的赋形剂在本领域是公知的。
西洋参果总皂苷制备治疗冠心病、心肌缺血、心律不齐、糖尿病等药物,是由有效成分单体或有效成分与固体或液体的赋形剂一起构成的。下面举几个具体的例子:散剂如果是服的粉末剂,它的赋形剂有乳糖、淀粉、浆糊精、碳酸钙、磷酸钙、合成的或天然的硅酸铝、氧化镁、无水氧化铝、硬脂酸镁、碳酸氢钠、干燥酵母等,其剂型包括冲剂、片剂、胶囊剂等;溶液剂的赋形剂有水、甘油、丙二醇、单糖浆、乙醇、脂油、乙二醇、聚乙二醇、山梨糖醇、木糖醇等;
有效物质的剂量可以根据服用方式、病人的年龄、体重及病情严重程度和其他类似的因素而改变。日用量为:口服200mg-300mg,分二次服用。
用西洋参果总皂苷制备的治疗冠心病、心肌缺血、心律不齐、糖尿病药物,其优点是疗效好、无毒副作用、价格低廉等。
本发明通过下面的实验进一步说明。
本发明的药物用途
1.1西洋参果总皂苷(PQFS)对犬急性心肌梗塞的影响
目的:观察西洋参果总皂苷对杂种犬实验性心肌梗塞的影响。方法:采用冠脉前降支结扎法,造成急性心肌梗塞。给予西洋参果总皂苷1、2、4mg/kg,异搏定0.2mg/kg,iv,观察血流动力学指标和血气指标,包括:心电图ECG、计算心率HR、血压BP、左室内压LVSP、左室舒张期末压LVEDP、左室内压最大变化速率±dp/dt、冠脉血流量CBF、心输出量Co、动脉氧分压、静脉氧分压、动脉血氧饱和度、静脉血氧饱和度及二级数据:心肌血流量MBF、心搏出量SV、心脏指数CI、心搏指数SI、左室作功、冠脉阻力CVR、总外周阻力TPVR、心肌耗氧量、心肌耗氧指数、心肌氧利用率%、动脉血氧含量、静脉血氧含量;测量心外膜电图EECG,心肌梗塞范围N-ST计算心肌梗塞程度∑-ST;检测血清肌酸激酶CK、乳酸脱氢酶LDH、天门冬氨酸氨基转移酶AST;称重心肌梗塞面积占全心及左室重量%。结果:西洋参果总皂能明显增加CBF、Co、MBF、CI、SI、血氧饱和度;显著减少+dp/dt、SV、CVR;降低心肌缺血范围和缺血程度,血清LDH、AST含量下降,并缩小心肌梗塞面积。结论:西洋参果总皂苷能减轻心肌缺血的损伤,对心脏有保护作用。
1.1.1实验材料
1.1.1.1药品 西洋参果总皂苷 由吉林大学基础医学院化学教研室提供,白色粉末,试验前用生理水配制成所需浓度。异搏定注射液,上海禾丰制药有限公司生产,生产批号:990401。戊巴比妥钠,上海化学试剂分装厂,批号:84-06-12。氯化硝基四氮唑兰,上海前进化学试剂厂生产,批号:20000502。盐酸利多卡因注射液,上海第二军医大学朝晖制药厂生产,批号:990405。
生化试剂 天门冬氨酸氨基转移酶AST试剂盒,肌酸激酶CK试剂盒,乳酸脱氢酶LDH试剂盒,均由北京众生康生物技术开发中心生产,批号:20010501。
1.1.1.2动物 杂种犬,体重10kg-17kg,由吉林大学实验动物部提供。
1.1.1.3 仪器RM-6000型多导生理记录仪,MFV-3200型电磁流量计,均由日本光电公司生产。EOS880型半自动血液生化分析仪,意大利生产,Corning158血气分析仪,美国生产。SC-3电动呼吸机,上海医疗设备厂生产。
1.1.2实验方法
健康杂种犬30只,随机分为5组,每组6只,用30mg/kg戊巴比妥钠溶液麻醉,iv。背位固定,用烧灼器切开颈部皮肤,分离气管进行气管插管,连接人工呼吸机,正压2-3kPa;分离左侧颈总动脉,插管连接压力换能器,测定动脉血压(BP);分离右侧股动脉,插心室导管,连接压力换能器,记录LVSP,经耦合放大器,记录LVEDP,经微分处理器记录±dp/dt;分离右侧股静以备给药用;用针式电极刺入四肢皮下,记录标II导联心电图(ECG),计算心率(HR)。
犬右侧卧位,沿胸骨左侧第4肋间开胸,去掉第4肋骨,用肋骨牵开器牵开肋骨,暴露心脏,将心包膜提起做心包床,分离主动脉根部,放置适宜电磁流量计探头,测定主动脉流量即心输量Co;分离冠状动脉前降支下1/3处,备线待结扎用;分离冠状动脉左旋支,放置适宜电磁流量计探头,测定冠脉流量CBF;用湿布式电极,测量心外膜电图EECG。记录24点,一点放置正常区,其余23点分放置于梗塞边缘区和梗塞中心区。
手术完毕,稳定10分钟。然后记录正常血流动力学各项指标和EECG;取动脉A血和静脉V血测血气值,取V血5ml进行离心,分离血清,待测血清肌酸激酶CK、乳酸脱氢酶LDH和天门冬氨酸转移酶AST。
结扎前iv盐酸利多卡因,防止心律失常。然后结扎冠脉前降支下1/3处,如心肌缺血EECG不明显,再结扎冠脉前降支1/2处,造成心肌缺血模型,记录心肌缺血时及给药后5、10、20、30、45、60、90、120、150、180、240min血流动力学各项指标;记录心肌缺血及药后5、10、20、30、45、60、90、120、180、240、300、360minEECG变化。以ST段升高总mv数,∑-ST;表示心肌缺血程度,以ST段抬高≥2mv的导联数表示心肌缺血范围,N-ST;检测心肌缺血、药后60、120、180、240min血气值及心肌缺血6h的血清心肌三酶含量;实验结束摘取心脏称全心重;沿冠状沟切除心房,称左室重。然后平行状将心室切成1cm厚的心肌片,剪下结扎线下1cm处心肌组织1cm3,放入10%福尔马林溶液中固定,做光镜病理切片检查;将心肌片放入0.1%的氯化硝基四氮唑兰溶液中染色,于37度恒温水浴温孵10分钟左右,取出用滤纸吸去水分,将非梗塞区染成兰色的组织剪去,称重梗塞区心肌组织重量,按称重法计算梗塞心肌组织占全心或左心室重量的百分率。
将血流动力学一级数据按公式计算二级数据,包括心肌血流量、心搏出量、心脏指数、心搏指数、左室作功、冠脉阻力、总外周阻力、心肌耗氧量、心肌耗氧指数、心肌氧利用率、动脉和静脉血氧含量。所有实验数据用均值±标准差
表示,进行组间实测值及变化百分率t检验分析。
1.1.3实验结果
1.1-3.1对±dp/dt的影响
(1)对+dp/dt的影响
西洋参果总皂苷小剂量1.0mg/kg、中剂量组2.0mg/kg对+dp/dt无明显影响。西洋参总皂苷大剂量组(4.0mg/kg)在药后20-180min+dp/dt的百分率明显低于盐水对照组,两组相比,有显著差异,P<0.05,P<0.01。异搏定组药后5-60min+dp/dt百分率明显低于盐水对照组,两组相比有明显差异,P<0.05.P<0.01。
(2)对-dp/dt的影响
西洋参果总皂苷小剂量组和大剂量组对-dp/dt无明显影响。而中剂量组在药后30min时-dp/dt明显低于盐水对照组,两组相比差异显著,P<0.05。异搏定组在药后30min-dp/dt显著低于盐水对照组,两组相比,P<0.05。
1.1.3.2对CBF的影响
西洋参果总皂苷小剂量组在药后10minCBF明显高于盐水对照组,两组相比差异显著,P<0.05。西洋参果总皂苷中剂量组在药后30minCBF显著高于盐水对照组,P<0.05。西洋参果总皂苷大剂量组在药后5-45minCBF明显增高,P<0.05。异搏定组在药后5-90minCBF明显增加,与盐水对照组相比,差异显著,P<0.05,P<0.01。其药后20-30minCBF的上升百分率显著高于盐水对照组,P<0.05,P<0.01。
1.1.3.3对Co的影响
西洋参果总皂苷各剂量组,给药后Co逐渐减少,但小剂量组在240min时Co仍高于盐水对照组,两组比较差异显著,P<0.05。异搏定组在药后45minCo明显低于盐水对照组,两组相比,有显著差异,P<0.05。
1.1.3.4对MBF的影响
西洋参果总皂苷小剂量组对MBF无明显影响。中剂量组在药后各时间点均可增加MBF,与盐水对照组比较差异显著,P<0.05,P<0.01。大剂量组在药后5-45minMBF明显高于盐水对照组,两组相比,有显著差异,P<0.05。异搏定组药后20-30minMBF上升百分率明显高于盐水对照组,两组比较差异显著,P<0.05,P<0.01,见表1。
表1 PQFS对心肌梗塞犬心肌血流量(ml/100g/min)的影响(x±s,N=6)
盐水组 | 异搏定0.2mg/kg | PQFS | |||
mg/kg | 2mg/kg | 4mg/kg | |||
正常0梗塞5分%10分%20分%30分%45分%60分%90分%120分%150分%180分%240分% | 211.59±41.83149.90±20.61155.69±15.444.40±5.48152.11±16.811.84±4.03154.12±15.843.33±5.78150.54±17.20.78±4.52155.03±11.784.39±10.07156.73±13.805.46±10.30155.61±16.284.75±12.77154.39±19.973.24±5.90151.82±17.281.83±8.44148.33±13.59-0.32±8.57144.75±14.05-2.92±5.38 | 192.24±29.17147.46±19.58165.09±30.2511.57±9.67167.96±35.8413.16±12.40172.35±32.9916.43±10.74*173.15±29.1017.31±9.83**166.56±31.2213.51±17.76168.22±32.3214.72±18.97167.52±34.4714.02±19.04155.44±33.455.24±14.84156.72±35.836.21±17.43149.83±29.271.58±12.93147.17±29.76-0.39±12.30 | 200.05±27.74147.00±19.78156.25±15.027.21±11.96156.25±15.277.21±12.03157.27±15.497.86±11.40161.33±20.210.94±16.83157.94±15.418.24±10.53155.87±15.276.80±10.07156.88±17.377.17±7.03153.65±15.355.08±6.84153.08±14.994.75±7.86151.62±15.853.66±7.22141.75±13.00-2.93±7.27 | 237.63±36.44177.23±28.39186.00±24.86*5.43±5.52184.17±24.51*4.35±4.64186.74±24.74*5.81±4.41185.39±24.49*5.08±4.78198.20±28.80**12.20±6.17209.52±40.69*20.51±32.58187.39±30.45*5.79±5.55186.40±26.96*5.44±3.91187.76±29.12*6.12±5.53185.41±26.91*5.02±7.08181.45±28.64*2.45±2.78 | 227.10±12.46167.74±11.47184.42±22.40*9.65±6.19175.96±18.08*4.71±3.82178.38±19.03*6.13±4.32172.93±17.11*2.92±3.31187.56±23.14*11.49±6.82175.40±19.944.34±5.39175.40±19.944.34±5.39175.40±19.944.34±5.39173.42±18.113.23±4.93168.59±22.930.20±7.78165.06±23.44-1.89±8.70 |
与盐水对照组比较*P<0.05,**P<0.01
1.1.3.5对SI的影响
西洋参果总皂苷小剂量组在药后240min时SI的下降百分率明显低于盐水对照组,两组比较差异显著,P<0.05。西洋参果总皂苷其余各组对SI无明显影响。异搏定组对SI无明显影响。
1.1.3.6对CVR影响
西洋参果总皂苷小剂量、大剂量组对CVR无明显影响。西洋参果总皂苷中剂量组药后5、20、45、60、120-240min多个时间点CVR明显降低,与盐水对照组相比,差异显著,P<0.05。异搏定组合在药后5-45、90minCVR的下降百分率明显高于盐水对照组,两组相比差异显著,P<0.05,P<0.01,P<0.001。
1.1.3.7对EECG的影响
(1)对N-ST的影响
西洋参果总皂苷小剂量组在给药后45-120min、36minN-ST明显低于盐水对照组,P<0.05,其降低百分率明显高于盐水对照组,P<0.05。中剂量组在药后45-360minN-ST明显小于盐水对照组,两组相比差异显著,P<0.05,其20-180、240-360minN-ST的下降百分率明显高于盐水对照组,P<0.05。西洋参果总皂苷大剂量组在药后90-180minN-ST明低于盐水对照组,P<0.05,其降低百分率明显高于盐水对照组,与盐水对照组相比差异显著,P<0.05异搏定组在药后45min、90-360minN-ST明显小于盐水对照组,两组相比差异显著,P<0.05,P<0.01。其45-360minN-ST的降低百分率明显高于盐水对照组,P<0.05。
(2)对∑-ST的影响
西洋参果总皂苷小剂量在药后90min∑-ST明显低于盐水对照组,两组比较差异显著,P<0.05,药后20-120min其下降百分率明显高于盐水对照组,两组比较有显著差异,P<0.05,P<0.01。西洋参果总皂苷中剂量组在药后90-120min∑-ST显著低于盐水对照组,P<0.01,P<0.05,药后20-360min∑-ST的下降百分率明显高于盐水对照组,P<0.05,P<0.01。西洋参果总皂苷大剂量组在药后60-360min∑-ST比盐水组轻,其下降百分率明显高于盐水对照组,P<0.05,P<0.01。异搏定组药后60-360min∑-ST明显轻于盐水对照组,与盐水对照组相比有显著差异,P<0.05,P<0.01,药后10-360min的降低百分率明显高于盐水对照组P<0.05,P<0.01,P<0.001,见表2。
表2 PQFS对心肌梗塞犬缺务程度(∑-STmv)的影响(x±s,N=6)
盐水组 | 异搏定0.2mg/kg | PQFS | |||
1.0mg/kg | 2.0mg/kg | 4.0mg/kg | |||
正常梗塞5分%10分%20分%30分%45分%60分%90分%120分%150分%180分%240分%300分% | 18.25±11.88139.83±38.15118.59±29.75-10.50±29.48107.00±13.62-19.33±21.19112.08±20.70-17.30±14.26109.42±20.59-19.34±13.23112.92±22.98-15.96±20.18109.42±34.02-20.34±17.83120.83±25.20-9.18±25.92114.08±31.18-17.55±12.46109.92±38.44-20.53±17.97101.67±32.36-24.92±22.5299.75±26.21-26.43±17.08101.33±34.20-27.80±9.93 | 29.92±6.14164.42±47.95105.92±42.61-36.78±10.9089.00±34.76-45.83±13.74*77.25±36.13-54.23±12.14***87.92±37.09-47.72±11.73**85.58±30.59-47.69±13.86**70.58±24.47*-56.49±11.90**62.92±15.28***-58.92±15.75**68.50±13.51**-56.92±9.53U57.38±14.50*-62.32±15.06**52.42±14.92**-67.21±7.88*58.83±24.45*-63.78±11.56**53.67±22.66*-67.03±10.05*** | 23.75±7.15138.83±22.3298.92±25.83-29.22±12.0699.42±26.10-28.15±15.1487.88±24.94-37.26±11.14*85.92±35.7439.84±17.28*83.33±36.86-41.91±18.73*75.42±16.62-45.61±10.01*78.50±25.60*-43.95±14.80*82.58±15.98-40.26±9.46**79.83±27.75-42.33±18.3090.00±26.65-34.52±17.9276.25±15.83-44.53±10.5981.42±34.92-41.54±20.74 | 20.08±8.95157.17±22.21118.83±27.17-24.78±9.91113.17±21.85-27.94±9.9496.33±27.39-38.38±17.45*94.50±21.74-39.04±16.53*85.33±22.75-44.87±15.90*76.25±22.65-49.51±14.33*74.00±22.08**-51.82±16.69**72.50±20.68*-52.98±15.01**74.25±19.07-52.04±13.54**76.25±18.97-50.64±15.23*77.92±25.91-49.83±18.24*66.42±33.50-56.10±24.56* | 27.17±5.06131.83±24.9499.92±21.82-24.34±7.6598.00±17.36-24.65±13.8392.42±16.10-29.21±10.4680.83±23.87-37.82±20.4982.50±30.42-36.39±26.1769.25±22.75*-46.65±19.14*67.17±19.48**-49.40±9.68**65.33±29.69*-52.14±11.05***62.83±21.55*-53.24±7.52**58.50±21.59*-56.63±8.81**57.08±20.14*-57.33±10.97**63.25±24.02*-53.00±12.06** |
与盐水对照组比较*P<0.05,**P<0.01,***P<0.001.
1.1.3.8对血清酶的影响
西洋参果总皂苷小剂量组给药后AST明显低于盐水对照组,两组相比,差异显著,P<0.05,对CK、LDH无明显影响。西洋参果总皂苷中剂量组给莼后LDH含量明显降低,其下降百分率明显低于盐水对照组,P<0.05,其AST、CK值与盐水组比较无显著差异。西洋参果总皂苷大剂量组AST和LDH含量下降百分率明显低于盐水对照组,P<0.05,P<0.01。异搏定组给药后AST、LDH含量显著下降,其下降百分率明显低于盐水对照组,两组相比,差异显著,P<0.05,P<0.01。
1.1.3.9对心肌梗塞面积的影响
西洋参果总皂苷小剂量组心肌心梗重量占全心重%明显低于盐水对照组,两组相比,差异显著,P<0.05。西洋参果总皂苷中剂量、大剂量组心梗面积占全心、左室重%均明显低于盐水对照组,有非常显著意义,P<0.05,P<0.01。异搏定组给药后心梗重量占全心、左室重量%均明显低于盐水对照组,两组相比,差异显著,P<0.05,P<0.01,见表3。
表3 PQFS对心肌梗塞犬梗塞面积的影响(x±s,N=6)
盐水组 | 异搏定0.2mg/kg | PQFS | |||
1mg/kg | 2mg/kg | 4mg/kg | |||
占全心%占左心% | 7.97±1.49410.54±2.07 | 4.65±2.12*5.48±1.77** | 3.25±1.79*7.58±5.15 | 6.05±0.63*8.10±0.89* | 4.22±1.85*5.82±2.45** |
与盐水对照组比较*P<0.05,**P<0.01.
1.1.3.10对心肌梗塞病理切片的影响
盐水对照组心肌梗死病变较明显、较重,而阳性药物组及给药组病变均较盐水组有明显减轻,尤其大剂量组病变量轻,说明该药具有一定的抗心肌缺血作用,且剂量越大,效果越明显。
1.1.4实验结论
西洋参果总皂苷能减轻心肌缺血损伤,增加心肌供血,对心脏有保护作用,适用治疗心肌缺血、冠心病和心律不齐等心血管系统疾病。
1.2西洋参果总皂苷对Wistar大鼠高血糖动物模型的影响
西洋参果总皂苷0.52g/kg、0.26/kg、0.13g/kg(分别相当于临床等效用量的8倍、4倍、2倍)大、中、小三个剂量组,其中大、中剂量组可使Wistar大鼠高血糖动物模型血糖水平下降,具有明显统计学意义P<0.05,与消渴丸组2.0g/kg,相当于临床等效用量的4倍,具有相似的作用;可使全血高切比粘度、全血低切比粘度下降,与模型组比较具有明显统计学意义P<0.05,P<0.01,大、中剂量组可使血浆粘度明显下降,与模型组比较具有明显统计学意义P<0.05。
西洋参果总皂苷0.90/kg、0.45g/kg、0.09g/kg,分别相当于临床等效用量的10倍、5倍、1倍,对昆明种小鼠糖耐量曲线影响实验结果表明,给予葡萄糖后30分钟,西洋参果总皂苷大剂量组血糖值下降与模型组比较有明显差异P<0.05,其余各给药组血糖值低于模型组,但无统计学意义。给予葡萄糖60分钟,各组血糖值明显升高,其中西洋参果总皂苷各组及消渴丸组血糖值低于模型组,但无统计学意义P>0.05,可120分钟时各组血糖值均恢复正常。
1.2.1实验材料
药品 西洋参果总皂苷,由吉林大学基础医学院天然药物研究室提供,批号:20000708;消渴丸由广州中药一厂生产,批准文号:(1994)第11146号,专利号:ZL953081990。
动物wistar大鼠,雌雄各半,体重195g-245g,由吉林大学实验动物部提供,质量合格证号:医动字第10-5110号:主要试剂和仪器
链脲霉素 (STZ)美国sigma化学公司出品,批号:89H0604
血糖试条 北京怡成生物电子技术有限公司出品。
JPS-III型快速血糖测试仪 北京怡成生物电子技术有限公司出品。
离心机 北京医用离心机厂,型号:LDZ5-2。
全自动生化仪 日本日立公司出品,型号:日立7170A型。
1.2.2试验方法
自吉林大学动物部引入Wistar大鼠后,饲养与吉林大学基础医学院动物室,室温22-2℃,湿度30-60%,饲料组成:玉米面39%、豆饼面25%、麦糠面14%、高粱面10%、骨粉2.5%、鱼粉5%、酵母3.5%、添加剂1%。
取西洋参果总皂苷药粉配成5.2%(g/v)、2.6%(g/v)、1.3%(g/v)大、中、小三个剂量的供量的供试药液。消渴丸配成浓度为20%(g/v)供试液。
自吉林大学动物部引入Wistar大鼠106只,雌雄各半,在本室适应1周,禁食不禁水4小时后,称体重、测血糖、作标记。选择血糖值在正常范围内、状态好的100只雌雄各半的大鼠做实验,从中留10只作为正常对照组,将90只Wistar大鼠用链脲霉素STZ按0.054g/kg造模型,链脲霉素STZ用0.05mol/L枸椽酸溶液PH=4.5配成2.0%的溶液。大鼠禁食不禁水16小时后按体重腹腔一次注入链脲霉素STZ药液。第8天禁食不禁水4小时后,测血糖,其中血糖值大于10mmol/L为模型成立。与正常对照组比较有显著性差异,P<0.001。将54只高血糖模型动物,随机分为五组,每组10~11只,雌雄各组均分。分组为:正常对照组、模型组、消渴丸组2.0g/kg,相当于临床用量的4倍、西洋参果总皂苷大剂量组0.52g/kg、中剂量组0.26g/kg、小剂量组0.13g/kg,相当于临床用量的8、4、2倍。
模型组给水10ml/kg,各给药组均给予10ml/kg供试药液。每日上午9时左右灌胃给药,连续四周,每周测血糖、体重,按新体重计算药量一次。于给药第四周后处死动物,取血测血常规、血液生化指标、血液流变学和胰岛素含量,并取胰腺进行病理组织学检查。将各组所得结果以均值x±标准差S表示,结果与模型组进行组间t检验,判断其显著性。
1.2.3试验结果
1.2.3.1对血糖的影响
给药后第三周西洋参果总皂苷大剂量组与模型组比较血糖明显下降(P<0.05)。第四周西洋参果总皂苷大、中剂量组和消渴丸组血糖值均降低,与模型组比较,具有明显统计学意义,P<0.05,见表4。
组别剂量动物(只) | 正常对照组10 | 模型组10ml/kg8 | 消渴丸组20g/kg9 | 大剂量组0.52g/kg10 | 中剂量组0.26g/kg9 | 小剂量组0.13/kg8 |
给药前一周二周三周四周 | 6.12±0.536.19±0.556.12±0.416.12±0.315.85±0.46 | 17.52±2.4017.15±2.2315.85±3.0214.09±3.5213.80±4.12 | 17.22±3.2216.85±3.0614.57±3.0211.97±2.539.36±2.83* | 17.04±3.3415.54±3.2313.57±2.6010.93±2.58*9.07±2.78* | 17.10±2.6315.10±2.3614.06±2.5311.71±2.729.49±1.98* | 16.37±3.3215.72±3.1015.12±3.2313.05±3.2611.81±3.36 |
与模型组比较*P<0.05
1.2.3.2对血液生化指标的影响
西洋参果总皂苷大、中剂量组和消渴丸组的血糖值与模型组比较均有明显下降,具有统计学意义(P<0.05),消渴丸组、大剂量组的总蛋白(TP)与模型组比较有明显升高,具有统计学意义(P<0.01),西洋参果总皂苷大剂量组的尿素氮BUN与模型组比较有所降低,具有统计学意义(P<0.05),见表5。
表5西洋参果总皂苷对糖尿病大鼠生化指标的影响
组别 | 正常对照组 | 模型组 | 消渴丸组 | 大剂量组 | 中剂量组 | 小型量组 |
剂量 | 10ml/kg | 2.0g/kg | 0.52g/kg | 0.26g/kg | 0.13g/kg | |
动物(只) | 10 | 8 | 9 | 10 | 9 | 8 |
ALT(U/L) | 42.7±20.2 | 101.0±32.6 | 112.6±58.8 | 100.9±55.2 | 108.2±45.9 | 133.5±85.4 |
AST(U/L) | 87.1±27.3 | 157.5±49.2 | 163.8±66.2 | 171.9±97.5 | 187.7±81.9 | 215.4±133.0 |
ALP(U/L) | 204.3±139.0 | 532.4±156.1 | 600.1±256.9 | 390.0±181.9 | 530.1±234.4 | 669.4±201.9 |
TP(g/L) | 62.3±4.1 | 61.2±3.5 | 66.7±2.5** | 66.4±3.3** | 64.6±3.5 | 62.9±6.1 |
ALB(g/L) | 34.5±3.5 | 30.2±2.4 | 31.2±1.8 | 33.7±4.1 | 32.3±2.4 | 32.9±2.0 |
TBIL(umol/L) | 0.37±0.23 | 0.39±0.34 | 0.17±0.11 | 0.36±0.32 | 0.24±0.20 | 0.45±0.43 |
BUN(mmol/L) | 8.1±0.8 | 11.2±4.5 | 8.9±1.0 | 7.5±1.6* | 8.8±0.9 | 8.8±1.6 |
CRE2(umol/L) | 58.5±4.7 | 82.5±29.5 | 69.8±7.7 | 64.4±4.8 | 66.1±5.8 | 68.3±6.7 |
GLU(mmol/L) | 6.07±1.82 | 13.98±4.94 | 9.33±3.29* | 8.68±2.78* | 9.27±2.78* | 11.58±3.82 |
CHO(mmol/L) | 1.3±0.2 | 1.4±0.5 | 1.2±0.2 | 1.4±0.4 | 1.2±0.1 | 1.2±0.1 |
与模型组比较*P<0.05,**P<0.01
1.4实验结论
西洋参果总皂苷PQFS具有降低大鼠实验性糖尿病的生物活性。
具体实施方式
本发明西洋参果总皂苷提取、精制方法
实施例一:
a.提取:取1.0kg西洋参果肉,溶于3L水中,在室温下,搅拌,100rpm,提取2h,提取3次,滤过,合并滤过液,0.07Mpa减压浓缩至一定体积,密度1.102,得西洋参果总皂苷粗品:
b.精制:取粗西洋参果总皂苷,上大孔吸附树脂D101,先用水洗至无色,改用10%乙醇洗脱至无色,最后用95%的乙醇洗脱,收集洗脱液,回收至干,得西洋参果总皂苷产品,产率20%。
实施例二:
a.提取:取1.0kg西洋参果肉,溶于3L水中,在室温下,搅拌,100rpm,提取3h,提取2次,滤过,合并滤过液,0.07Mpa减压浓缩至一定体积,密度1.192,得西洋参果总皂苷粗品;
b.精制:取粗西洋参果总皂苷,上大孔吸附树脂D4020,先用水洗至无色,改用15%乙醇洗脱至无色,最后用75%的乙醇洗脱,收集洗脱液,回收至干,得西洋参果总皂产品,产率15%。
实施例三:
a.提取:取1.0kg西洋参果肉,溶于3L水中,在室温下,搅拌,100rpm,提取3h,提取2次,滤过,合并滤过液,减压浓缩(0.07Mpa)至一定体积,密度1.192,得西洋参果总皂苷粗品:
b.精制:取粗西洋参果总皂苷,上大孔吸附树脂AB-8,先用水洗至无色,改用20% 醇洗脱至无色,最后用50%的乙醇洗脱,收集洗脱液,回收至干,得西洋参果总皂产品,产率15%。
制备药物实施方式
实施例一:
西洋参果总皂苷 25g
淀粉 13g
将西洋参果总皂苷与淀粉混合均匀,装入胶囊,0.25g/粒,制成1000粒,压板,灭菌即可。
实施例二:
西洋参果总皂苷 250g
山梨酸 10g
乙醇 100ml
取西洋参果总皂苷溶解于乙醇中,加入山梨酸后,用制药用水稀释至10000nl,过滤,灌瓶,10ml/瓶,制成1000瓶,蒸汽灭菌30min,即可。
Claims (1)
1、西洋参果总皂苷提取物在制备治疗冠心病、心肌缺血及心律不齐和II型糖尿病的药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03127613 CN1325509C (zh) | 2003-07-08 | 2003-07-08 | 西洋参果总皂苷提取物在制备药物中的用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03127613 CN1325509C (zh) | 2003-07-08 | 2003-07-08 | 西洋参果总皂苷提取物在制备药物中的用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1482136A CN1482136A (zh) | 2004-03-17 |
CN1325509C true CN1325509C (zh) | 2007-07-11 |
Family
ID=34153192
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 03127613 Expired - Fee Related CN1325509C (zh) | 2003-07-08 | 2003-07-08 | 西洋参果总皂苷提取物在制备药物中的用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1325509C (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100335071C (zh) * | 2004-04-27 | 2007-09-05 | 吉林省宏久生物科技股份有限公司 | 一种西洋参果软胶囊的制备方法 |
CN100441592C (zh) * | 2004-04-27 | 2008-12-10 | 吉林省宏久生物科技股份有限公司 | 西洋参果甙提取方法 |
CN101940350B (zh) * | 2010-07-05 | 2012-09-19 | 赵景辉 | 一种具有镇静、安神作用的人参果冲剂及其制备工艺 |
CN102988441B (zh) * | 2012-12-24 | 2014-11-26 | 李平亚 | 一种西洋参果提取物的用途 |
-
2003
- 2003-07-08 CN CN 03127613 patent/CN1325509C/zh not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN1482136A (zh) | 2004-03-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107080250A (zh) | 一种辅助降血糖的组合物、饮料及其制备方法 | |
CN101033245B (zh) | 具栖冬青苷的制备方法及应用 | |
CN1931236B (zh) | 一种由丹参和红景天制成的药物组合物 | |
CN101278939B (zh) | 治疗心脑血管疾病的药物组合物及其制备方法 | |
CN101099753A (zh) | 救必应总皂苷的制备方法及应用 | |
CN1923241B (zh) | 包括淫羊藿提取物、钩藤提取物、天麻素的药物组合物及其制备方法和应用 | |
CN1325509C (zh) | 西洋参果总皂苷提取物在制备药物中的用途 | |
CN102716135B (zh) | 羽扇豆酮在制备预防或治疗糖尿病的产品中的应用 | |
CN107648479A (zh) | 一种用于治疗高血压的中药组方及其制品 | |
CN100377731C (zh) | 一种中药及其制备方法和用途 | |
CN100467025C (zh) | 积雪草总苷、积雪草苷或羟基积雪草苷在制备防治心、脑血管疾病药物中的用途 | |
CN104161798B (zh) | 一种复方丹参提取物及其应用 | |
CN101032534B (zh) | 救必应总皂苷的制备方法及应用 | |
CN101336965A (zh) | 一种用于改善糖耐量、降低血糖的中成药及其制备方法 | |
CN1970050B (zh) | 一种治疗心率失常的药物组合物及其制备方法 | |
CN100478002C (zh) | 治疗冠心病的复方缬草药物及其制备工艺 | |
CN1923228B (zh) | 三七提取物、丹参提取物和川芎嗪的药物组合物 | |
CN100356952C (zh) | 一种治疗心力衰竭的中药组合物及其口服制剂 | |
CN101099754A (zh) | 具栖冬青苷的制备方法及应用 | |
CN1923229B (zh) | 三七提取物、丹参提取物和葛根素的药用组合物 | |
CN106620253B (zh) | 一种治疗缓慢性心律失常的中药组合物 | |
CN110664828A (zh) | 一种麦冬皂苷d制剂及其降血糖药物新用途 | |
CN101991757B (zh) | 一种补肾助阳的中药组合物及其制备方法 | |
CN1582946B (zh) | 积雪草酸衍生物在制备防治心、脑血管疾病的药物中的用途 | |
CN103520260B (zh) | 一种治疗冠心病心绞痛的药物组合及制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term |
Granted publication date: 20070711 |
|
CX01 | Expiry of patent term | ||
CI03 | Correction of invention patent |
Correction item: Termination upon expiration of patent Correct: Revocation of Patent Expiration and Termination False: On July 25, 2023, the expiration and termination of the 39-volume 3001 patent Number: 30-01 Volume: 39 |
|
CI03 | Correction of invention patent | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070711 |