CN102670711B - White flower salviae miltiorrhizae extract for curing angiitis, preparation method and application - Google Patents
White flower salviae miltiorrhizae extract for curing angiitis, preparation method and application Download PDFInfo
- Publication number
- CN102670711B CN102670711B CN 201210178921 CN201210178921A CN102670711B CN 102670711 B CN102670711 B CN 102670711B CN 201210178921 CN201210178921 CN 201210178921 CN 201210178921 A CN201210178921 A CN 201210178921A CN 102670711 B CN102670711 B CN 102670711B
- Authority
- CN
- China
- Prior art keywords
- extraction
- extract
- salvia miltiorrhiza
- ethanol
- salviae miltiorrhizae
- 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
- 239000000284 extract Substances 0.000 title claims abstract description 98
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- GVKKJJOMQCNPGB-UHFFFAOYSA-N Cryptotanshinone Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)CO2 GVKKJJOMQCNPGB-UHFFFAOYSA-N 0.000 claims abstract description 15
- GVKKJJOMQCNPGB-JTQLQIEISA-N Cryptotanshinone Chemical compound O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1[C@@H](C)CO2 GVKKJJOMQCNPGB-JTQLQIEISA-N 0.000 claims abstract description 15
- SNKFFCBZYFGCQN-UHFFFAOYSA-N 2-[3-[3-[1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyloxy]-3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound C=1C=C(O)C=2OC(C=3C=C(O)C(O)=CC=3)C(C(=O)OC(CC=3C=C(O)C(O)=CC=3)C(O)=O)C=2C=1C=CC(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-UHFFFAOYSA-N 0.000 claims abstract description 14
- SNKFFCBZYFGCQN-VWUOOIFGSA-N Lithospermic acid B Natural products C([C@H](C(=O)O)OC(=O)\C=C\C=1C=2[C@H](C(=O)O[C@H](CC=3C=C(O)C(O)=CC=3)C(O)=O)[C@H](OC=2C(O)=CC=1)C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-VWUOOIFGSA-N 0.000 claims abstract description 14
- STCJJTBMWHMRCD-UHFFFAOYSA-N salvianolic acid B Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=O)C=Cc2cc(O)c(O)c3OC(C(C(=O)OC(Cc4ccc(O)c(O)c4)C(=O)O)c23)c5ccc(O)c(O)c5 STCJJTBMWHMRCD-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000000746 purification Methods 0.000 claims abstract description 11
- 229940079593 drug Drugs 0.000 claims abstract description 10
- 238000000638 solvent extraction Methods 0.000 claims abstract description 8
- 238000004440 column chromatography Methods 0.000 claims abstract description 7
- 150000007965 phenolic acids Chemical class 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 157
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 claims description 105
- 239000000243 solution Substances 0.000 claims description 62
- 239000007787 solid Substances 0.000 claims description 52
- 238000000605 extraction Methods 0.000 claims description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 239000002994 raw material Substances 0.000 claims description 23
- 239000007864 aqueous solution Substances 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 17
- 239000007788 liquid Substances 0.000 claims description 16
- 239000000706 filtrate Substances 0.000 claims description 15
- 230000003156 vasculitic effect Effects 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 claims description 11
- 239000003208 petroleum Substances 0.000 claims description 11
- 238000010025 steaming Methods 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- 239000002244 precipitate Substances 0.000 claims description 10
- 241000304195 Salvia miltiorrhiza Species 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000012141 concentrate Substances 0.000 claims description 8
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 238000010898 silica gel chromatography Methods 0.000 claims description 7
- DOUMFZQKYFQNTF-WUTVXBCWSA-N (R)-rosmarinic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-WUTVXBCWSA-N 0.000 claims description 6
- 230000014759 maintenance of location Effects 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- 241000196324 Embryophyta Species 0.000 claims description 5
- 239000002893 slag Substances 0.000 claims description 5
- 238000002137 ultrasound extraction Methods 0.000 claims description 5
- 239000003480 eluent Substances 0.000 claims description 4
- 239000002024 ethyl acetate extract Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- YMGFTDKNIWPMGF-AGYDPFETSA-N 3-(3,4-dihydroxyphenyl)-2-[(e)-3-[2-[(e)-2-(3,4-dihydroxyphenyl)ethenyl]-3,4-dihydroxyphenyl]prop-2-enoyl]oxypropanoic acid Chemical compound C=1C=C(O)C(O)=C(\C=C\C=2C=C(O)C(O)=CC=2)C=1/C=C/C(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-AGYDPFETSA-N 0.000 claims description 3
- NEZONWMXZKDMKF-JTQLQIEISA-N Alkannin Chemical compound C1=CC(O)=C2C(=O)C([C@@H](O)CC=C(C)C)=CC(=O)C2=C1O NEZONWMXZKDMKF-JTQLQIEISA-N 0.000 claims description 3
- ZZAFFYPNLYCDEP-HNNXBMFYSA-N Rosmarinsaeure Natural products OC(=O)[C@H](Cc1cccc(O)c1O)OC(=O)C=Cc2ccc(O)c(O)c2 ZZAFFYPNLYCDEP-HNNXBMFYSA-N 0.000 claims description 3
- YMGFTDKNIWPMGF-QHCPKHFHSA-N Salvianolic acid A Natural products OC(=O)[C@H](Cc1ccc(O)c(O)c1)OC(=O)C=Cc2ccc(O)c(O)c2C=Cc3ccc(O)c(O)c3 YMGFTDKNIWPMGF-QHCPKHFHSA-N 0.000 claims description 3
- 238000010298 pulverizing process Methods 0.000 claims description 3
- DOUMFZQKYFQNTF-MRXNPFEDSA-N rosemarinic acid Natural products C([C@H](C(=O)O)OC(=O)C=CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-MRXNPFEDSA-N 0.000 claims description 3
- TVHVQJFBWRLYOD-UHFFFAOYSA-N rosmarinic acid Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=Cc2ccc(O)c(O)c2)C=O TVHVQJFBWRLYOD-UHFFFAOYSA-N 0.000 claims description 3
- 241001071917 Lithospermum Species 0.000 claims description 2
- UNNKKUDWEASWDN-UHFFFAOYSA-N alkannin Natural products CC(=CCC(O)c1cc(O)c2C(=O)C=CC(=O)c2c1O)C UNNKKUDWEASWDN-UHFFFAOYSA-N 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 229930183118 Tanshinone Natural products 0.000 claims 3
- 239000006228 supernatant Substances 0.000 claims 1
- AIGAZQPHXLWMOJ-UHFFFAOYSA-N tanshinone IIA Natural products C1=CC2=C(C)C=CC=C2C(C(=O)C2=O)=C1C1=C2C(C)=CO1 AIGAZQPHXLWMOJ-UHFFFAOYSA-N 0.000 abstract description 23
- 239000007901 soft capsule Substances 0.000 abstract description 15
- 206010043540 Thromboangiitis obliterans Diseases 0.000 abstract description 14
- HYXITZLLTYIPOF-UHFFFAOYSA-N Tanshinone II Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)=CO2 HYXITZLLTYIPOF-UHFFFAOYSA-N 0.000 abstract description 13
- AZEZEAABTDXEHR-UHFFFAOYSA-M sodium;1,6,6-trimethyl-10,11-dioxo-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-2-sulfonate Chemical compound [Na+].C12=CC=C(C(CCC3)(C)C)C3=C2C(=O)C(=O)C2=C1OC(S([O-])(=O)=O)=C2C AZEZEAABTDXEHR-UHFFFAOYSA-M 0.000 abstract description 13
- 239000006187 pill Substances 0.000 abstract description 10
- 239000002775 capsule Substances 0.000 abstract description 8
- 239000003826 tablet Substances 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 239000007938 effervescent tablet Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 4
- YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 238000012869 ethanol precipitation Methods 0.000 abstract 1
- 244000132619 red sage Species 0.000 description 97
- 229960004756 ethanol Drugs 0.000 description 44
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 241000700159 Rattus Species 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 9
- -1 phenolic acid compounds Chemical class 0.000 description 9
- 239000008107 starch Substances 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- 208000033386 Buerger disease Diseases 0.000 description 8
- 238000011026 diafiltration Methods 0.000 description 8
- 210000003414 extremity Anatomy 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 231100000915 pathological change Toxicity 0.000 description 6
- 230000036285 pathological change Effects 0.000 description 6
- 239000000080 wetting agent Substances 0.000 description 6
- 229920001353 Dextrin Polymers 0.000 description 5
- 239000004375 Dextrin Substances 0.000 description 5
- 208000025865 Ulcer Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 235000019425 dextrin Nutrition 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 231100000397 ulcer Toxicity 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- 229960004106 citric acid Drugs 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 239000012567 medical material Substances 0.000 description 4
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000011257 shell material Substances 0.000 description 4
- 238000003809 water extraction Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 206010017577 Gait disturbance Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 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 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 206010047115 Vasculitis Diseases 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229940083542 sodium Drugs 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000015424 sodium Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010017711 Gangrene Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 229920001202 Inulin Polymers 0.000 description 2
- FEFAIBOZOKSLJR-UHFFFAOYSA-N Miltirone Chemical compound C1CCC(C)(C)C=2C1=C1C(=O)C(=O)C(C(C)C)=CC1=CC=2 FEFAIBOZOKSLJR-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 240000007164 Salvia officinalis Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000000469 ethanolic extract Substances 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 2
- 229940029339 inulin Drugs 0.000 description 2
- 210000000629 knee joint Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000009959 nanxing Substances 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000005325 percolation Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000005412 red sage Nutrition 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 2
- 235000010378 sodium ascorbate Nutrition 0.000 description 2
- 229960005055 sodium ascorbate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical group [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- PAFLSMZLRSPALU-MRVPVSSYSA-N (2R)-3-(3,4-dihydroxyphenyl)lactic acid Chemical compound OC(=O)[C@H](O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-MRVPVSSYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WTPPRJKFRFIQKT-UHFFFAOYSA-N 1,6-dimethyl-8,9-dihydronaphtho[1,2-g][1]benzofuran-10,11-dione;1-methyl-6-methylidene-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-10,11-dione Chemical compound O=C1C(=O)C2=C3CCCC(=C)C3=CC=C2C2=C1C(C)=CO2.O=C1C(=O)C2=C3CCC=C(C)C3=CC=C2C2=C1C(C)=CO2 WTPPRJKFRFIQKT-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229920002101 Chitin Polymers 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
- PAFLSMZLRSPALU-QMMMGPOBSA-N Danshensu Natural products OC(=O)[C@@H](O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-QMMMGPOBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-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
- 239000005639 Lauric acid Substances 0.000 description 1
- 244000147568 Laurus nobilis Species 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- PAFLSMZLRSPALU-UHFFFAOYSA-N Salvianic acid A Natural products OC(=O)C(O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 239000007766 cera flava Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 210000001255 hallux Anatomy 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000002818 limb ischemia Diseases 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 210000004906 toe nail Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to a white flower salviae miltiorrhizae extract for curing angiitis, a preparation method and an application. The white flower salviae miltiorrhizae extract is extracted from white flower salviae miltiorrhizae roots through a solvent extraction, a solvent extraction, an ethanol precipitation and column chromatography purification. The white flower salviae miltiorrhizae extract is a mixture composed of total phenanthrenequinone and total phenolic acid of the white flower salviae miltiorrhizae. The total of mass of cryptotanshinone, tanshinone IIA and salvianolic acid B is no less than 60%. The white flower salviae miltiorrhizae extract has a good curing function to thromboangitis obliterans (TAO), is capable of well reflecting an overall treatment effect of white flower salviae miltiorrhizae original medicinal materials on the TAO, is capable of being manufactured into tablets, capsules, soft capsules, medicines to be taken dissolved in water, effervescent tablets or dropping pills according to a pharmaceutic conventional production technology and is used for curing the TAO.
Description
Technical field
The present invention relates to a kind of Chinese medicine extract, more specifically say a kind of White flower danshen total phenanthrenequinone formed by the Salvia miltiorrhiza f. extraction and the extract that always phenolic acid forms, preparation method and the purposes aspect the vasculitic pharmaceutical composition for the treatment of thereof.
Background technology
Thromboangiitis obliterans (Thromboangitis Obliterans, TAO) a kind ofly take the chronic occlusion disease that thrombosis is feature in medium and small arteriovenous segmental, nonsuppurative inflammation and lumen of artery, be apt to occur in lower limb, the course of disease is long, be more and delay into property and increase the weight of gradually, often cause limbs generation ischemia or blood stasis disease damage, very person's limbs fester and come off, and are a kind of chronic peripheral vascular diseases.The traditional Chinese medical science is referred to as " necrosis ", in Huangdi's Internal Classics, in " Ling Shu Miraculous Pivot or Divine Axis carbuncle " and Han dynasty " Huatuo highly skilled doctor secretly hands down ", discussion is all arranged.
Salvia miltiorrhiza f. (Salvia miltiorrhiza Bunge var alba) is the modification of labiate Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge), and main product is in knobs such as Zhangqiu, Shandong, Laiwu, Tai'an.Within 2002, Salvia miltiorrhiza f. is incorporated into " Shandong Province's Chinese crude drug standard " as new varieties.Record in " national Chinese herbal medicine compilation ": Salvia miltiorrhiza f. likeness in form Radix Salviae Miltiorrhizae (also claims Radix Salviae Miltiorrhizae, 2010 editions pharmacopeia are recorded), the thought floral white, what have can be slightly purple dizzy, also with root, is used as medicine, and originates in Shandong, local useful Salvia miltiorrhiza f. wine treatment thromboangiitis obliterans person, referring to national Chinese herbal medicine compilation [first volume], People's Health Publisher, 1975.
The Salvia miltiorrhiza f. root is used for the treatment of the vasculitis history of existing more than 80 years, referring to Xu Qingfeng, and treatment and healthy medicated wine, 1988, p117.Shandong Province Zhangqiu County hospital applied Salvia miltiorrhiza f. treatment TAO since 1967, from in October, 1971 to 1975 year December application Salvia miltiorrhiza f. treatment vasculitis 147 examples, clinical cure rate 27.2%, remarkable improvement rate 45.6%, total effective rate 93.2%, through treatment, and clinical grouping comparison is observed, the curative effect of Salvia miltiorrhiza f. is higher than Radix Salviae Miltiorrhizae, referring to Journal of Traditional Chinese Medicine, 1976, (11): 23-24.Professor Shang Dejun of former Attached Hospital of Shandong College of Traditional Chinese Medicine (existing Hospital Attached to Shandong Chinese Medical Univ.) waits in treatment TAO process, find 1 routine III phase, 1 grade of (damp heat downward flowing type) patient, the disunion in 9 months in 2 years of right sufficient big toe chronic ulcer, give the intravenous drip of Salvia miltiorrhiza f. injection after 15 days, suffering limb blood fortune is improved, and ulcer healing, referring to Shang Dejun etc., Shandong journal of Chinese medicine, 1986 (2): 14-16.
CN1899371A(CN200610045270.X) provide the application of a kind of Salvia miltiorrhiza f. in pharmaceutical field and the preparation method of white flower red sage medicine.The content of Danshensu of Salvia miltiorrhiza f. is the twice of pale reddish brown Radix Salviae Miltiorrhizae, and this material is used for the treatment of cardiovascular and cerebrovascular disease and other relevant diseases, has the effect of the silt pain relieving of dispelling, promoting blood circulation to restore menstrual flow, the relieving restlessness that clears away heart-fire.The preparation method of described white flower red sage medicine is: 1. get Salvia miltiorrhiza f. and insert in extraction pot, add the water of 4～10 times of weight portions to carry out water extraction, filter to obtain water extraction liquid; Or will carry out supersound extraction after the Salvia miltiorrhiza f. micronizing, filter to obtain the ultra micro extract powder; 2. get the ultra micro extract powder of 1. operation or through being concentrated into the water extraction liquid that relative density is 1.0～1.4, add 50%～90% ethanol to carry out the alcohol precipitation, after filtering with 20%～40% highly basic, solution is adjusted pH=6.5～8.5, coldly put rear filtration, repeat the alcohol precipitation, obtain filtrate; 3. will be 2. the filtrate of operation to be concentrated into relative density be 1.0～1.4, add 0.5%～2% active carbon, heated and boiled, obtain liquid agent.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, a kind of Salvia miltiorrhiza f. extract, preparation method are provided and have prepared the purposes for the treatment of medicine for treating angitis object space face.Salvia miltiorrhiza f. extract in the present invention contains total phenanthrenequione and total large class active component of phenolic acid two in Salvia miltiorrhiza f. simultaneously, can fully demonstrate the Salvia miltiorrhiza f. crude drug to vasculitic therapeutical effect.
The present invention also provides pharmaceutical composition and the preparation of Salvia miltiorrhiza f. extract.
The term explanation:
The Salvia miltiorrhiza f. extract is the mixture that the multiple phenolic acid compounds such as the multiple phenanthrenequione classes such as tanshinone ⅡA contained in Salvia miltiorrhiza f., cryptotanshinone, Tanshinone I, miltirone and salvianolic acid A, salvianolic acid B, rosmarinic acid, shikonin form.
Technical solution of the present invention is as follows:
A kind ofly treat vasculitic Salvia miltiorrhiza f. extract, the root of Salvia miltiorrhiza f. of take is raw material, by solvent extraction, solvent extraction, precipitate with ethanol, column chromatography purification, be prepared from, contain total phenanthrenequione and total large class active component of phenolic acid two in Salvia miltiorrhiza f. simultaneously, be the mixture that mainly contains the liposoluble ingredients such as the phenanthrenequione constituents such as tanshinone ⅡA, cryptotanshinone, Tanshinone I and salvianolic acid A, salvianolic acid B, rosmarinic acid, shikonin, wherein the mass content summation of tanshinone ⅡA, cryptotanshinone and salvianolic acid B is not less than 60%.
The present invention treats vasculitic Salvia miltiorrhiza f. extract, is to prepare by the method comprised the following steps:
The root of Salvia miltiorrhiza f. of take is raw material, and after pulverizing, methanol or 95wt% ethanol are extracted for extracting solvent, and the weight ratio of described quantity of solvent and raw material is 5 ~ 20: 1, repeats to extract 2 ~ 3 times, and merging filtrate, obtain extracting solution A; The raw material medicinal residues are extracted with 10 ~ 50wt% ethanol, 10 ~ 50wt% methanol aqueous solution or water again, obtain extracting solution B.The gained extracting solution is processed by the following method:
I. extracting solution A is evaporated to without ethanol or without methanol, with aqueous suspension, and with isopyknic dichloromethane extraction, re-extract 2 ~ 3 times, the aqueous solution C after obtaining dichloromethane extraction liquid and extracting.Dichloromethane extraction liquid pressure reducing and steaming solvent wherein, obtain solid residue, again this solid residue is carried out to silica gel column chromatography, petroleum ether-ethyl acetate with 50: 1 volume ratios and 1: 1 volume ratio carries out eluting respectively, collect the eluent of 1: 1 volume ratio of petroleum ether-ethyl acetate, the pressure reducing and steaming solvent, obtain red solids I.
Ii extracting solution B concentrating under reduced pressure, adding ethanol to make ethanol content is 70 ~ 75wt%, precipitate with ethanol, discard precipitation, filtrate decompression is concentrated into without ethanol, concentrate is mixed to stirring and evenly mixing with the aqueous solution C in i, adjust pH=2 ~ 3 with hydrochloric acid, again with isopyknic ethyl acetate extraction, re-extract 2 ~ 3 times, combined ethyl acetate extract, the pressure reducing and steaming ethyl acetate, obtain the solids II.
Above solids I and solids II are merged, and porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.
Above-mentioned ii extracting solution B is evaporated to 1 times of raw material slag weight and is advisable.
According to the present invention, a kind of preparation method for the treatment of vasculitic Salvia miltiorrhiza f. extract, detailed step is as follows:
(1) solvent extraction
The root of raw material Salvia miltiorrhiza f. is through after pulverizing, and take methanol, 95wt% ethanol to be extracted as extracting solvent, and the weight ratio of solvent for use amount and raw material is 5 ~ 20: 1, repeats to extract 2 ~ 3 times, and merging filtrate, obtain extracting solution A; The raw material slag is extracted with 10 ~ 50wt% ethanol, 10 ~ 50wt% methanol aqueous solution or water again, obtains extracting solution B.
Preferably, described extracting method is with heating extraction, ultrasonic extraction, diafiltration extraction method or plant tissue Smashing extraction method.
Preferably, in heating extraction, ultrasonic extraction and plant tissue Smashing extraction method, extraction solvent load used is raw material weight 5 ~ 10 times, in the diafiltration extraction method, extraction solvent load used is raw material weight 20 times.
(2) extraction of extracting solution A, column chromatography purification
Extracting solution A is evaporated to without ethanol under 50 ℃ of conditions, adds the water of crude drug 4 ~ 6 times of weight, suspend, and with isopyknic dichloromethane extraction, re-extract 2 ~ 3 times, the aqueous solution C after obtaining dichloromethane extraction liquid and extracting.Pressure reducing and steaming solvent under 50 ℃ of conditions of dichloromethane extraction liquid wherein, obtain solid residue, again this solid residue is carried out to purification by silica gel column chromatography, first with 5 ~ 8 retention volumes of 50: 1 volume ratio eluting of petroleum ether-ethyl acetate, with 1: 1 volume ratio eluting of petroleum ether-ethyl acetate, 12 ~ 18 retention volumes of eluting, collect the eluent of 1: 1 volume ratio of petroleum ether-ethyl acetate again, pressure reducing and steaming solvent under 50 ℃ of conditions, obtain red solids I.
(3) precipitate with ethanol of extracting solution B, acidify, extraction
Extracting solution B is evaporated to 1 times of weight of raw material slag weight under 50 ℃ of conditions, the ethanol that adds 95wt%, making ethanol content in solution is 70 ~ 78wt%, placement is spent the night, the filtering precipitation, filtrate is evaporated to without ethanol under 50 ℃ of conditions, the concentrate of gained mixes with the aqueous solution C after gained extraction in step (2), stir, then with 2N hydrochloric acid, solution is adjusted to pH=2～3, then with isopyknic ethyl acetate extraction, re-extract 2 ~ 3 times, the combined ethyl acetate extract, the pressure reducing and steaming ethyl acetate, obtain the solids II.
(4) combining solid thing I and solids II, porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.
The tanshinone ⅡA of the inventive method gained Salvia miltiorrhiza f. extract, cryptotanshinone and and the quality total content of salvianolic acid B be not less than 60%.
The pharmaceutical applications of Salvia miltiorrhiza f. extract of the present invention, for the preparation of the vasculitic medicine for the treatment of, especially for the medicine of preparation treatment thromboangiitis obliterans.
The pharmaceutical preparation that different dosage form is made in Salvia miltiorrhiza f. extract of the present invention and pharmaceutic adjuvant combination, be used for the treatment of vasculitis.
A kind of pharmaceutical composition for the treatment of vasculitic Salvia miltiorrhiza f. extract, comprise one of Salvia miltiorrhiza f. extract of the present invention and pharmaceutically acceptable carrier, excipient, antioxidant or combination.
Preferably, described antioxidant is selected from sodium ascorbate, ascorbic acid, citric acid or sodium pyrosulfite.
Preferably, one of the tablet that described pharmaceutical composition is the Salvia miltiorrhiza f. extract, capsule, electuary, soft capsule preparation, drop pill, effervescent tablet, can prepare according to the pharmaceutics conventional production process.
The pharmaceutical preparation of described pharmaceutical composition different dosage form is described in detail as follows:
1, the preparation of Salvia miltiorrhiza f. extract tablet, capsule or electuary, all by the percentage by weight of Salvia miltiorrhiza f. extract total amount:
Get described Salvia miltiorrhiza f. extract, add the diluent I of 2 ~ 6 times of weight, the wetting agent of 4 ~ 15wt%, the disintegrating agent of 5 ~ 15wt%, wet granulation routinely, drying, granulate, pack, obtain electuary; Perhaps the granule after granulate is added to the lubricant of 0.5 ~ 3wt% again, mix, incapsulate that shell obtains capsule or tabletting obtains tablet.
Above-mentioned diluent I is selected from starch, Icing Sugar, dextrin or microcrystalline cellulose;
Above-mentioned wetting agent is selected from water or ethanol;
Above-mentioned disintegrating agent is carboxymethyl starch sodium;
Above-mentioned lubricant is magnesium stearate or Pulvis Talci.
2, the preparation of Salvia miltiorrhiza f. extract soft capsule agent
Get described Salvia miltiorrhiza f. extract, add diluent II, mix, then add antioxidant, suspending agent, stir, room temperature is standing, obtains the medicinal liquid of Salvia miltiorrhiza f. phenanthrenequinone extract soft capsule content; By mould, it is pressed into to soft capsule together with the prior soft capsule shell material prepared with gelatin, glycerol, antiseptic.
Above-mentioned diluent II is selected from vegetable oil;
Above-mentioned antioxidant is selected from sodium ascorbate, citric acid or sodium pyrosulfite;
Above-mentioned suspending agent is selected from Cera Flava, chitin methylcellulose or agar.
3, the preparation of Salvia miltiorrhiza f. extract dripping pill
Get described Salvia miltiorrhiza f. extract, add appropriate dehydrated alcohol, then add in Macrogol 4000 or polyethylene glycol 6000 fused solution, 60 ℃ of constant temperature water baths stir, until ethanol is waved to the greatest extent; Then this fused solution is proceeded in the surge drum of pill dripping machine, under the insulation condition of 80～85 ℃, splash into condensed fluid, collect drop pill.
Preferably, the weight ratio of described Salvia miltiorrhiza f. extract and Macrogol 4000 is 1: 4 ~ 6.
4, the preparation of Salvia miltiorrhiza f. extract effervescent tablet
The Salvia miltiorrhiza f. extract is divided into to two parts, be A part and B part, first by A part with beta-cyclodextrin inclusion compound, the mass ratio 0.4 ~ 0.8: 1 of A part and beta-schardinger dextrin-, with the sodium bicarbonate of 8 ~ 10wt% or sodium carbonate, filler, 1 ~ 3%PVP (polyvinyl pyrrolidone) anhydrous alcohol solution of take is made alkali grain as wetting agent; By B part and 10 ~ 12% acid sources, filler, correctives inulin, mix, 1 ~ 3%PVP anhydrous alcohol solution of take is made acid particles as wetting agent.Then two kinds of granules are mixed, then add lubricant, tabletting.
Preferably, described filler is one of starch, dextrin, lactose, mannitol, sucrose or combination; ;
Preferably, described acid source is selected from one of citric acid, tartaric acid, fumaric acid, adipic acid, malic acid or combination; ;
Preferably, described lubricant have soluble oil as Macrogol 4000, polyethylene glycol 6000, sodium lauryl sulphate and water-insoluble lubricant as magnesium stearate, Pulvis Talci, micropowder silica gel, select a kind of or 2 ~ 3 kinds of combinations in them.
Salvia miltiorrhiza f. extract of the present invention and drug combination preparation thereof are used for the treatment of thromboangiitis obliterans, improve the caused chronic ulcer of limb ischemia, pain, feel cold and intermittent limping, promote ulcer healing.
The pharmacodynamic study of the vasculitic Salvia miltiorrhiza f. extract for the treatment of of the present invention.
Animal: 56 of Wistar male rats, body weight 280 ~ 300g, provided by Shandong University's Experimental Animal Center.
Reagent and instrument: TONGSAIMAI PIAN (Jiangsu Nanxing Pharmaceutical Co., Ltd), lot number: Z32020535, lauric acid (Chemical Reagent Co., Ltd., Sinopharm Group), lot number: F200909284; Thromboxance B
2, 6-ketone-prostaglandin F
1 α, the ET enzyme exempts from test kit (RD company), lot number is 201203.
Medicine: will prepare the Salvia miltiorrhiza f. extract according to embodiment 1 method, and be mixed with the suspension of 0.1g/ml, 0.05g/ml and 0.025g/ml with 0.5% sodium carboxymethyl cellulose solution.To treat clinically at present the positive contrast of oral medicine TONGSAIMAI PIAN commonly used (Jiangsu Nanxing Pharmaceutical Co., Ltd's production) of thromboangiitis obliterans, by its porphyrize, cross 80 mesh sieves, be mixed with the suspension of 0.132g/ml with 0.5% sodium carboxymethyl cellulose solution.
Modeling and grouping: adopt Femoral Artery Injection Laurel acid system, prepare Thromboangitis Obliterans Model in Rat.By 56 rats, be sham operated rats, model group, TONGSAIMAI PIAN group, Salvia miltiorrhiza f. extract high dose group, middle dosage group and low dose group at random.
Administration: adopt the administration by gavage administration.The Salvia miltiorrhiza f. extract suspension of high, medium and low three kinds of variable concentrations that Salvia miltiorrhiza f. extract high dose group, middle dosage group and low dose group give to have prepared according to the dosage of 0.8g/kg, 0.4g/kg and 0.2g/kg respectively.The TONGSAIMAI PIAN suspension solution that the TONGSAIMAI PIAN group gives to have prepared according to the dosage of 0.66g/kg.Each group is gastric infusion after operation all, administration every day 1 time, continuous 1 week.
Experimental result:
The rat sign Index is observed: gross examination of skeletal muscle rat suffering limb skin color, temperature, suffering limb have or not swelling, have or not degree, the limping situation of gangrene and gangrene.With reference to Wang Jun etc., Chinese combination of Chinese and Western medicine magazine, 1996,16 (7): 421-423.The grade scale classification adopted, the I level: pathological changes is confined to toenail section; The II level: pathological changes is confined to toe; The III level: pathological changes is confined to sufficient claw; The IV level: pathological changes is confined to below knee joint; The V level: pathological development is to more than knee joint.Experimental result is in Table 1, and the pathological changes of model group is the most serious, and the pathological changes of TONGSAIMAI PIAN group and the high, medium and low dosage group of Salvia miltiorrhiza f. extract is the lightest, with model group, compares, and high, middle dosage group has utmost point significant difference P<0.01, low dosage significant difference P<0.05.
The impact that table 1 Salvia miltiorrhiza f. extract changes the local sign of TAO rat
Annotate: with sham operated rats, compare,
△ △p<0.01; With model group, compare,
*p<0.01,
*p<0.05.
Biochemical Indices In Serum is measured: determination experiment rat blood serum TXB
2, 6-K-PGF
1 α, ET content, the results are shown in Table 2.With sham operated rats, compare, every biochemical indicator of model group rat blood serum has utmost point significant difference, and the establishment of TAO rat model is described; Compare 6-K-PGF in TONGSAIMAI PIAN group and the high, medium and low dosage group of Salvia miltiorrhiza f. extract serum with model group
1 αcontent significantly raises, TXB
2, ET content significantly reduces, and utmost point significant difference P<0.01 is all arranged, and shows that the Salvia miltiorrhiza f. extract can improve the anti-thrombus function of modeling rat aorta, vascular endothelial cell is had to protective effect.
Table 2 Salvia miltiorrhiza f. extract is to TAO rat blood serum TXB
2, 6-K-PGF
1 α, ET impact
Annotate: with sham operated rats, compare,
△ △p<0.01; With model group, compare,
*p<0.01
Above-mentioned experimental result shows, the vasculitic Salvia miltiorrhiza f. extract for the treatment of of the present invention has antithrombotic and forms, improves the suffering limb blood circulation, alleviates the effect of suffering limb inflammatory reaction, can be used for treating thromboangiitis obliterans, and the suffering limb chronic ulcer, the pain that by it, are caused, feel cold and intermittent limping, there are good effect, characteristics easy to use.
With the TONGSAIMAI PIAN that is used for the treatment of clinically at present thromboangiitis obliterans, compare, wherein in the Salvia miltiorrhiza f. extract, the dosage group is better than the TONGSAIMAI PIAN group, illustrates that spending Radix Salviae Miltiorrhizae extract in vain can be applicable to clinically the treatment to thromboangiitis obliterans.This extract can be processed into various dosage forms according to the pharmaceutics conventional production process, as tablet, capsule, electuary, soft capsule and drop pill.
The high-performance liquid chromatogram determination of Salvia miltiorrhiza f. extract of the present invention.
The Salvia miltiorrhiza f. extract of take in embodiment 1 is measured its high-efficient liquid phase chromatogram (HPLC) as example.Because the polarity difference of the solids I that forms the Salvia miltiorrhiza f. extract and solids II is larger, therefore, the chromatographic condition of measuring their HPLC is also different.
The HPLC chromatographic condition of solids I: take octadecylsilane chemically bonded silica as filler; Chromatographic column is AgilentEclipse XDB-C18 post (250mm * 4.6mm); Take 0.05% phosphate aqueous solution as mobile phase A, take acetonitrile as Mobile phase B; UV detects wavelength: 270nm; The linear gradient elution temporal sequence is in Table 1; Flow velocity: 1.0mL/min; Sample size: 10 μ L.The HPLC spectrogram of the solids I surveyed is as accompanying drawing 1, the HPLC collection of illustrative plates that accompanying drawing 2 is cryptotanshinone, tanshinone Ⅰ and the tanshinone IIA standard substance measured under identical HPLC chromatographic condition.
Table 3 Salvia miltiorrhiza f. extracts the HPLC elution requirement of solids I
The HPLC chromatographic condition of solids II: take octadecylsilane chemically bonded silica as filler; Agilent EclipseXDB-C18 post (250mm * 4.6mm) chromatographic column; Take 0.05% phosphate aqueous solution as mobile phase A, take acetonitrile as Mobile phase B; UV detects wavelength: 286nm; The linear gradient elution temporal sequence is in Table 2; Flow velocity: 1.0mL/min; Sample size: 10 μ L.The HPLC spectrogram of the solids II surveyed is as accompanying drawing 3, the HPLC collection of illustrative plates that accompanying drawing 4 is the salvianolic acid B measured under identical HPLC chromatographic condition.
Table 4 Salvia miltiorrhiza f. extracts the HPLC elution requirement of solids II
The accompanying drawing explanation
Fig. 1 is the HPLC collection of illustrative plates of embodiment 1 Salvia miltiorrhiza f. solids I.
Fig. 2 is the HPLC collection of illustrative plates of standard substance cryptotanshinone, tanshinone Ⅰ and tanshinone IIA, cryptotanshinone 31.15min; Tanshinone Ⅰ 32.26min; Tanshinone IIA 41.6min.
Fig. 3 is the HPLC collection of illustrative plates of embodiment 1 Salvia miltiorrhiza f. solids II.
Fig. 4 is the HPLC collection of illustrative plates of reference substance salvianolic acid B.
The specific embodiment
Below in conjunction with embodiment, the present invention will be further described, but be not limited to this.
Percent concentration in embodiment is mass percent.The column chromatography used in embodiment is with silica gel purchased from Qingdao Haiyang chemical company, and granularity is 200～300 orders.Flash extracter is purchased from Beijing gold tripod development in science and technology company limited, model JHBE-50S.Other solvents, pharmaceutic adjuvant and the equipment used in embodiment is well known in the art, but market is bought.Embodiment 1: a kind of preparation method for the treatment of vasculitic Salvia miltiorrhiza f. extract, and step is as follows:
1. the Salvia miltiorrhiza f. root after crushed, adds 8 times of amount 95% ethanol, reflux, extract,, and the 1st time 1.5 hours, the 2nd time 1 hour, extract altogether 2 times, merge 95% ethanol extract, obtain extracting solution A; The raw material medicinal residues add 8 times of water gagings again, heat 90 ℃ of extractions, and each 1 hour, extract altogether 2 times, merge aqueous extract, obtain extracting solution B.
2. extracting solution A is evaporated to without ethanol under 50 ℃ of conditions, the water that adds crude drug 5 times of weight, stirring suspension, then add and the isopyknic dichloromethane of water, re-extract 3 times, the aqueous solution C after dichloromethane extraction liquid and extraction, combined dichloromethane extract evaporated under reduced pressure, the gained solid residue is again with the acetone solution of its 26 times of weight, add the column chromatography of gained solid residue 12 times of weight to mix thoroughly with silica gel, volatilize, porphyrize, for mixing sample silica gel; Silica gel (the silica gel consumption is 60 times of solid residue weight) wet method dress post, to mix again the sample silica gel chromatographic column of packing into, first with 6 retention volumes of petroleum ether-ethyl acetate (50: 2 volume ratios) eluting, again with 15 retention volumes of petroleum ether-ethyl acetate (1: 1 volume ratio) eluting, collect the eluent of 1: 1 volume ratio of petroleum ether-ethyl acetate, the pressure reducing and steaming solvent, obtain the solids I;
3. extracting solution B is evaporated to 1 times of amount of crude drug medicinal residues weight under 50 ℃ of conditions, adds 95% ethanol of 3.5 times of amounts, stirs, placement is spent the night, precipitate with ethanol, filtering precipitation, filtrate is evaporated to without ethanol under 50 ℃ of conditions, and gained concentrate and step 2. the aqueous solution C of gained are mixed, and stir, then with 2N hydrochloric acid, solution is adjusted to pH=2, again with isopyknic ethyl acetate extraction, re-extract 3 times, combined ethyl acetate extract, the pressure reducing and steaming ethyl acetate, obtain the solids II.
4. combining solid thing I and solids II, porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.The Salvia miltiorrhiza f. extract is got middle cryptotanshinone, tanshinone ⅡA and salvianolic acid B mass content summation and is not less than 69%.
Embodiment 2:
The Salvia miltiorrhiza f. root after crushed, adds 8 times of amount methanol, reflux, extract,, and the 1st time 1.5 hours, the 2nd time 1 hour, extract altogether 2 times, merge methanol extract liquid, obtain extracting solution A; The raw material medicinal residues add 8 times of amount 50% alcohol reflux again, and each 1 hour, extract altogether 2 times, merge aqueous extract, obtain extracting solution B.Extracting solution A concentrating under reduced pressure, dichloromethane extraction, purification by silica gel column chromatography, implementation method, with embodiment 1, obtains solids I and extraction rear solution C; Extracting solution B concentrating under reduced pressure, the ethanol precipitate with ethanol, filter, and filtrate is concentrated, and concentrate mixes with the aqueous solution C obtained from extracting solution A, acidify, the ethyl acetate extraction, implementation method, with embodiment 1, obtains the solids II.Combining solid thing I and solids II, porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.The Salvia miltiorrhiza f. extract is got middle cryptotanshinone, tanshinone ⅡA and salvianolic acid B mass content summation and is not less than 65%.
Embodiment 3:
The Salvia miltiorrhiza f. root after crushed, adds 6 times of amount 95% ethanol, and under 50 ℃ of conditions, supersound extraction is 30 minutes, repeats to extract 4 times, and merge extractive liquid,, obtain extracting solution A; Medicinal residues add 6 times of amount 40% ethanol ultrasonic extraction 30 minutes again, extract altogether 4 times, merge 40% ethanol extract, obtain extracting solution B.Extracting solution A concentrating under reduced pressure, dichloromethane extraction, purification by silica gel column chromatography, implementation method is with embodiment 1, obtains the aqueous solution C after solids I and extraction; Extracting solution B concentrating under reduced pressure, the ethanol precipitate with ethanol, filter, and filtrate is concentrated, and concentrate mixes with the aqueous solution C obtained from extracting solution A, acidify, the ethyl acetate extraction, implementation method, with embodiment 1, obtains the solids II.Combining solid thing I and solids II, porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.The Salvia miltiorrhiza f. extract is got middle cryptotanshinone, tanshinone ⅡA and salvianolic acid B mass content summation and is not less than 66%.
Embodiment 4:
The Salvia miltiorrhiza f. root is after being ground into fine powder, put into container with lid, after adding again the even moistening of 95% ethanol of medical material amount 60% ~ 70% volume, place 2 hours, then pack in the diafiltration cylinder, mouth adds 95% ethanol from it, and percolate flows out from its end opening, and constantly from suitable for reading supplementing, add 95% ethanol, keep the ethanol in the diafiltration cylinder can soak medical material all the time.The rate of outflow of controlling percolate is 5 ~ 10ml/ minute, with the ethanol of 20 times of amounts of medical material volume, carries out diafiltration, collects 95% ethanol percolation liquid, obtains extracting solution A; Then the medicinal residues in the diafiltration cylinder are adopted to use the same method with 30% ethanol again and are carried out diafiltration, and flow velocity is with 95% ethanol, and diafiltration solvent for use total amount is 20 times of amounts of medical material volume, collects 30% ethanol percolation liquid, obtains extracting solution B.Extracting solution A is concentrated, dichloromethane extraction, and purification by silica gel column chromatography, implementation method is with embodiment 1, obtains the aqueous solution C after solids I and extraction; Extracting solution B concentrating under reduced pressure, the ethanol precipitate with ethanol, filter, and filtrate is concentrated, and concentrate mixes with the aqueous solution C obtained from extracting solution A, acidify, the ethyl acetate extraction, implementation method, with embodiment 1, obtains the solids II.Combining solid thing I and solids II, porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.The Salvia miltiorrhiza f. extract is got middle cryptotanshinone, tanshinone ⅡA and salvianolic acid B mass content summation and is not less than 67%.
Embodiment 5:
Raw material Salvia miltiorrhiza f. root after crushed, by 95% soak with ethanol 1 hour, then utilizes the broken plant tissue of flash extracter, under room temperature, 95% ethanol extraction is 2 times, adds respectively 8 times of amounts of raw material weight, 6 times of amounts, and extraction time is respectively 2 minutes, 1 minute, centrifugal filtration, merging filtrate, obtain extracting solution A; And then medicinal residues are at room temperature continued, with water extraction 2 times, to add respectively the water of 6 times of amounts of raw material weight, 6 times of amounts, extraction time is respectively 1 minute, 1 minute, centrifugal filtration, and merging filtrate, obtain extracting solution B.Extracting solution A concentrating under reduced pressure, dichloromethane extraction, purification by silica gel column chromatography, implementation method is with embodiment 1, obtains the aqueous solution C after solids I and extraction; Extracting solution B concentrating under reduced pressure, the ethanol precipitate with ethanol, filter, and filtrate is concentrated, and concentrate mixes with the aqueous solution C obtained from extracting solution A, acidify, the ethyl acetate extraction, implementation method, with embodiment 1, obtains the solids II.Combining solid thing I and solids II, porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.
The Salvia miltiorrhiza f. extract is got middle cryptotanshinone, tanshinone ⅡA and salvianolic acid B mass content summation and is not less than 65%.
Embodiment 6: Salvia miltiorrhiza f. extract medicinal composition tablets
The Salvia miltiorrhiza f. extract 200g of embodiment 1 gained, add starch 100g, dextrin 45g, cane sugar powder 5g, carboxymethyl starch sodium 17.5g, mix, granulation, dry under 60 ℃, granulate, add Pulvis Talci 1.5g, carboxymethyl starch sodium 17.5g, mix, and is pressed into 1000, obtains.
Embodiment 7: Salvia miltiorrhiza f. extract pharmaceutical composition electuary
The Salvia miltiorrhiza f. extract 50g of embodiment 3 gained, add starch 300g, dextrin 100g, microcrystalline Cellulose 50g, above solid matter ground 80 mesh sieves respectively, mixed, and added appropriate 10% starch slurry to make binding agent, made wet granular, dry under 60 ℃, granulate, be distributed into 100 bags, obtains.
Embodiment 8: the agent of Salvia miltiorrhiza f. extract medicament composition capsule
The Salvia miltiorrhiza f. extract 200g of embodiment 2 gained, add starch 150g, dextrin 45g, and microcrystalline Cellulose 3.5g, mix, granulation, dry under 60 ℃, granulate, add magnesium stearate 1.5g, mixes, and incapsulates 1000, shell, obtains.
Embodiment 9: the agent of Salvia miltiorrhiza f. extract medicinal composition soft capsule
The Salvia miltiorrhiza f. extract 100g of gained in the preparation of soft capsule content: embodiment 5, porphyrize, cross 100 mesh sieves, add in the 10g PEG-4000, heated and stirred, then add Oleum Arachidis hypogaeae semen 330g dilution, then add ascorbic acid 1.0g, p-Hydroxybenzoate 1.0g, cera alba 8g, be heated to 38 ℃ of left and right, stir simultaneously, obtain its soft capsule content; The preparation of soft capsule shell material: in parts by weight, by gelatin: glycerol: water: sorbic acid was according to mass ratio 1.0: 0.3: 0.85: 0.15 ratio is carried out proportioning, first will in a certain amount of glycerol, putting into of water glue tank, be heated to 65 ℃, and then by pharmagel, sorbitol inputization glue tank, stir, be heated to 65 ℃, pharmagel is dissolved fully, obtain capsule casing material; Soft capsule preparation: use encapsulating machine, the capsule casing material made is placed in the gelatin heat-preserving container of 70 ℃, the rubber of soft capsule processed, then inject the soft capsule content made, and rolls mold pressing and make 1000 soft capsules, and drying, wash ball, then drying, obtains.
Embodiment 10: Salvia miltiorrhiza f. extract medicament composition dropping pills
Get the Salvia miltiorrhiza f. extract 15g of gained in embodiment 4, add 30 ~ 50ml dehydrated alcohol, after slight fever is dissolved, filter, filtrate is added in the Macrogol 4000 fused solution of 85g, 60 ℃ of constant temperature water baths stir, until ethanol is waved to the greatest extent, eliminate bubble, then this fused solution is proceeded in the surge drum of pill dripping machine, be incubated dripping under 85 ℃ of conditions, drip apart from 3cm, take dimethicone as condensed fluid, control 20 ℃ to 0 ℃ gradients of condensate temperature cooling, treat that condensation is complete, condensed fluid inclines, collect drop pill, drop is clean and remove the condensed fluid on ball with filter paper, place in silica gel drier or natural drying), obtain approximately 1000 of drop pill.
Embodiment 11: Salvia miltiorrhiza f. extract pharmaceutical composition effervescent tablet
The 150g Salvia miltiorrhiza f. extract of getting in embodiment 1 is divided into two parts: A part and each 75g of B part.First the beta-cyclodextrin inclusion compound with 100g by A part, mix with 40g sodium bicarbonate, 20g mannitol, and the 1%PVP anhydrous alcohol solution of take is made alkali grain as wetting agent; By 50g lactic acid, 60g citric acid, 15g inulin, 30g mannitol, grind respectively, to cross sieve No. 7, partly mix with B, the 1%PVP anhydrous alcohol solution of take is made acid particles as wetting agent.Then two kinds of granules are mixed, then add the 10g polyethylene glycol 6000, be pressed into 1000.
Claims (2)
1. a preparation method for the treatment of vasculitic Salvia miltiorrhiza f. extract, the root of Salvia miltiorrhiza f. of take is raw material, being prepared from by solvent extraction, solvent extraction, precipitate with ethanol, column chromatography purification, containing total phenanthrenequione and total large class active component of phenolic acid two in Salvia miltiorrhiza f. simultaneously, is mainly to contain TANSHINONES
a, cryptotanshinone, TANSHINONES
the mixture of phenanthrenequione constituents and salvianolic acid A, salvianolic acid B, rosmarinic acid, shikonin liposoluble ingredient, wherein TANSHINONES
the mass content summation of A, cryptotanshinone and salvianolic acid B is not less than 60%;
Preparation process is as follows:
(1) solvent extraction
The root of raw material Salvia miltiorrhiza f. is through after pulverizing, and take methanol, 95wt% ethanol to be extracted as extracting solvent, and the weight ratio of solvent for use amount and raw material is 5 ~ 20:1, repeats to extract 2 ~ 3 times, and merging filtrate, obtain extracting solution A; The raw material slag is extracted with 10 ~ 50 wt% ethanol, 10 ~ 50 wt% methanol aqueous solutions or water again, obtains extracting solution B;
(2) extraction of extracting solution A, column chromatography purification
Extracting solution A is evaporated to without ethanol or without methanol under 50 ℃ of conditions, adds the water of crude drug 4 ~ 6 times of weight, suspend, and with isopyknic dichloromethane extraction, re-extract 2 ~ 3 times, the aqueous solution C after obtaining dichloromethane extraction liquid and extracting; Pressure reducing and steaming solvent under 50 ℃ of conditions of dichloromethane extraction liquid wherein, obtain solid residue, again this solid residue is carried out to purification by silica gel column chromatography, first with 5 ~ 8 retention volumes of petroleum ether-ethyl acetate 50:1 volume ratio eluting, with petroleum ether-ethyl acetate 1:1 volume ratio eluting, 12 ~ 18 retention volumes of eluting, collect the eluent of petroleum ether-ethyl acetate 1:1 volume ratio again, pressure reducing and steaming solvent under 50 ℃ of conditions, obtain the solids I;
(3) precipitate with ethanol of extracting solution B, acidify, extraction
Extracting solution B is evaporated to 1 times of weight of raw material slag weight under 50 ℃ of conditions, the ethanol that adds 95wt%, making ethanol content in solution is 70 ~ 78wt%, placement is spent the night, the filtering precipitation, supernatant is evaporated to without ethanol under 50 ℃ of conditions, the gained concentrate mixes with the aqueous solution C after gained extraction in step (2), stir, then with 2N hydrochloric acid, solution is adjusted to pH=2～3, then with isopyknic ethyl acetate extraction, re-extract 2 ~ 3 times, the combined ethyl acetate extract, the pressure reducing and steaming ethyl acetate, obtain the solids II;
(4) combining solid thing I and solids II, porphyrize, mix, and obtains the Salvia miltiorrhiza f. extract.
2. the preparation method of the vasculitic Salvia miltiorrhiza f. extract for the treatment of as claimed in claim 1, is characterized in that the extracting method described in step (1) is with heating extraction, ultrasonic extraction, permeating extraction or plant tissue Smashing extraction method.
3. the preparation method of the vasculitic Salvia miltiorrhiza f. extract for the treatment of as claimed in claim 2, it is characterized in that extraction solvent load used in heating extraction, ultrasonic extraction and plant tissue Smashing extraction method is raw material weight 6 ~ 10 times, in permeating extraction, extraction solvent load used is raw material weight 15 ~ 20 times.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210178921 CN102670711B (en) | 2012-06-01 | 2012-06-01 | White flower salviae miltiorrhizae extract for curing angiitis, preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210178921 CN102670711B (en) | 2012-06-01 | 2012-06-01 | White flower salviae miltiorrhizae extract for curing angiitis, preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102670711A CN102670711A (en) | 2012-09-19 |
| CN102670711B true CN102670711B (en) | 2013-12-18 |
Family
ID=46803697
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210178921 Expired - Fee Related CN102670711B (en) | 2012-06-01 | 2012-06-01 | White flower salviae miltiorrhizae extract for curing angiitis, preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102670711B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105477467A (en) * | 2015-12-08 | 2016-04-13 | 肇庆医学高等专科学校 | Heat-clearing dampness-eliminating tea effervescent tablet and preparation method thereof |
| CN106074665B (en) * | 2016-08-08 | 2019-08-20 | 齐鲁工业大学 | Extracting flavonoids method in a kind of mao of Lai leaf |
| CN107556313B (en) * | 2017-10-07 | 2019-11-01 | 扬州大学附属医院 | A kind of active constituent being isolated from Radix Salviae Miltiorrhizae and its application in treatment cranial vascular disease |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101601469B (en) * | 2008-06-11 | 2012-05-23 | 闫永亮 | Health care medicinal liquor and preparation method thereof |
-
2012
- 2012-06-01 CN CN 201210178921 patent/CN102670711B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN102670711A (en) | 2012-09-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2895335C (en) | Pharmaceutical composition for treating headache, and preparation method thereof | |
| CN102225138B (en) | Traditional Chinese medicine composition for treating fracture and preparation method and application thereof | |
| KR101088539B1 (en) | Chinese medicinal compositions for treating headache, formulations and processes for preparation therof | |
| CN102552396B (en) | Salvia miltiorrhiza Bunge var alba total phenolic acid extract, preparation method and application | |
| CN111358839B (en) | Formula granules of polygonum capitatum and preparation method thereof | |
| CN104706855A (en) | Preparation methods and application of Jichuan decoction traditional Chinese medicine extract | |
| CN102614281B (en) | Chinese medicinal composition for improving anoxia endurance and preparation method and application thereof | |
| CN102120020B (en) | Medicinal composition for treating hyperplastic diseases of breast and hysteromyoma and preparation method thereof | |
| CN101502579A (en) | Chinese medicinal composition for treating digestive tumor and preparation method thereof | |
| CN102670711B (en) | White flower salviae miltiorrhizae extract for curing angiitis, preparation method and application | |
| CN102100825A (en) | Chinese medicine composition for treating pains and preparation method thereof | |
| CN101156918B (en) | A medicine for treating gout and preparation method | |
| CN103768529A (en) | Traditional Chinese medicine composition for treating postchole cystomy syndrome and application thereof | |
| CN104173922B (en) | A kind of Chinese medicine for treating goiter | |
| CN101549075B (en) | Traditional Chinese medicine composition for treating mammary gland hyperplasia and preparation method thereof | |
| CN102512496B (en) | White flower danshen total phenanthrenequinone extract for treating angiitis, medicinal composition and preparation method | |
| CN104116753B (en) | The application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine | |
| CN103356731B (en) | Pharmaceutical composition containing Cortex Eucommiae extract and Radix Notoginseng total arasaponins and application thereof | |
| CN107638453B (en) | Fuyanting granules and preparation method thereof | |
| CN102188580B (en) | Externally used traditional Chinese medicine composition and cataplasm for treating lobular hyperplasia of mammary gland, and preparation methods thereof | |
| CN101269115B (en) | Cardiac and cerebral vascular disease treating medicament preparation and method for preparing the same | |
| CN109718283B (en) | Traditional Chinese medicine composition for relieving asthma and reducing phlegm and preparation method thereof | |
| CN1241625C (en) | Chinese medicine product with functions of detoxifying in 3 days and eliminating withdrawl syndrome | |
| CN114848710B (en) | Preparation and application of compound traditional Chinese medicine composition for treating chronic plasma cell mastitis | |
| CN114848730B (en) | Preparation and application of compound traditional Chinese medicine composition for treating acute plasma cell mastitis |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20131218 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |