CN1919240B - Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases - Google Patents
Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases Download PDFInfo
- Publication number
- CN1919240B CN1919240B CN2005100148391A CN200510014839A CN1919240B CN 1919240 B CN1919240 B CN 1919240B CN 2005100148391 A CN2005100148391 A CN 2005100148391A CN 200510014839 A CN200510014839 A CN 200510014839A CN 1919240 B CN1919240 B CN 1919240B
- Authority
- CN
- China
- Prior art keywords
- extract
- salviae miltiorrhizae
- radix salviae
- tanshinone
- phenolic acids
- 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
- 208000026106 cerebrovascular disease Diseases 0.000 title claims abstract description 18
- 208000024172 Cardiovascular disease Diseases 0.000 title claims abstract description 14
- 230000002526 effect on cardiovascular system Effects 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 title claims description 62
- 239000000284 extract Substances 0.000 claims abstract description 255
- AIGAZQPHXLWMOJ-UHFFFAOYSA-N Tanshinone I Chemical compound C1=CC2=C(C)C=CC=C2C(C(=O)C2=O)=C1C1=C2C(C)=CO1 AIGAZQPHXLWMOJ-UHFFFAOYSA-N 0.000 claims abstract description 232
- 229930183118 Tanshinone Natural products 0.000 claims abstract description 150
- 239000000203 mixture Substances 0.000 claims abstract description 66
- -1 panaxtriol saponins Chemical class 0.000 claims abstract description 61
- 150000007965 phenolic acids Chemical class 0.000 claims description 93
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 92
- 235000009048 phenolic acids Nutrition 0.000 claims description 92
- 238000000605 extraction Methods 0.000 claims description 43
- 239000000843 powder Substances 0.000 claims description 39
- 239000000706 filtrate Substances 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- 239000007788 liquid Substances 0.000 claims description 25
- 238000001035 drying Methods 0.000 claims description 24
- 239000006187 pill Substances 0.000 claims description 23
- 239000003480 eluent Substances 0.000 claims description 19
- 238000001914 filtration Methods 0.000 claims description 19
- 239000012567 medical material Substances 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 18
- 238000004321 preservation Methods 0.000 claims description 17
- 239000011347 resin Substances 0.000 claims description 17
- 229920005989 resin Polymers 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 15
- 238000010298 pulverizing process Methods 0.000 claims description 12
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 11
- 238000010828 elution Methods 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 11
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 11
- 238000010438 heat treatment Methods 0.000 claims description 10
- 238000002844 melting Methods 0.000 claims description 10
- 230000008018 melting Effects 0.000 claims description 10
- 235000003143 Panax notoginseng Nutrition 0.000 claims description 9
- 241000180649 Panax notoginseng Species 0.000 claims description 9
- 239000012141 concentrate Substances 0.000 claims description 9
- 229940057995 liquid paraffin Drugs 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 6
- 239000004952 Polyamide Substances 0.000 claims description 5
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 claims description 5
- 240000007164 Salvia officinalis Species 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 230000006837 decompression Effects 0.000 claims description 5
- 229920002647 polyamide Polymers 0.000 claims description 5
- 229940057838 polyethylene glycol 4000 Drugs 0.000 claims description 5
- 230000004087 circulation Effects 0.000 claims description 4
- 238000013461 design Methods 0.000 claims description 4
- 238000001291 vacuum drying Methods 0.000 claims description 4
- 235000017276 Salvia Nutrition 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 230000000274 adsorptive effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 26
- 206010008118 cerebral infarction Diseases 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 8
- 229930182490 saponin Natural products 0.000 abstract description 7
- 201000006474 Brain Ischemia Diseases 0.000 abstract description 6
- 206010008120 Cerebral ischaemia Diseases 0.000 abstract description 6
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 abstract description 5
- 208000031225 myocardial ischemia Diseases 0.000 abstract description 5
- 239000002253 acid Substances 0.000 abstract description 4
- 235000017709 saponins Nutrition 0.000 abstract 3
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 abstract 1
- 229940116229 borneol Drugs 0.000 abstract 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 abstract 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 abstract 1
- 239000010669 rosewood oil Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- PWAOOJDMFUQOKB-WCZZMFLVSA-N ginsenoside Re 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@](C)(CCC=C(C)C)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O PWAOOJDMFUQOKB-WCZZMFLVSA-N 0.000 description 12
- AOGZLQUEBLOQCI-UHFFFAOYSA-N ginsenoside-Re Natural products CC1OC(OCC2OC(OC3CC4(C)C(CC(O)C5C(CCC45C)C(C)(CCC=C(C)C)OC6OC(CO)C(O)C(O)C6O)C7(C)CCC(O)C(C)(C)C37)C(O)C(O)C2O)C(O)C(O)C1O AOGZLQUEBLOQCI-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 8
- 210000002216 heart Anatomy 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000002835 absorbance Methods 0.000 description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- YURJSTAIMNSZAE-UHFFFAOYSA-N UNPD89172 Natural products C1CC(C2(CC(C3C(C)(C)C(O)CCC3(C)C2CC2O)OC3C(C(O)C(O)C(CO)O3)O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O YURJSTAIMNSZAE-UHFFFAOYSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- YURJSTAIMNSZAE-HHNZYBFYSA-N ginsenoside Rg1 Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YURJSTAIMNSZAE-HHNZYBFYSA-N 0.000 description 5
- CBEHEBUBNAGGKC-UHFFFAOYSA-N ginsenoside Rg1 Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5CC(OC6OC(CO)C(O)C(O)C6O)C34C)C CBEHEBUBNAGGKC-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 210000003657 middle cerebral artery Anatomy 0.000 description 4
- 238000012856 packing Methods 0.000 description 4
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 4
- 150000007949 saponins Chemical class 0.000 description 4
- 235000012141 vanillin Nutrition 0.000 description 4
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 4
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 4
- 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 description 3
- 206010008190 Cerebrovascular accident Diseases 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
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 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 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000012496 blank sample Substances 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 210000003194 forelimb Anatomy 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 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 description 3
- 229920002545 silicone oil Polymers 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000004471 Glycine Substances 0.000 description 2
- 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 2
- 241000053227 Themus Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical group Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 235000005412 red sage Nutrition 0.000 description 2
- 210000001562 sternum Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 206010000117 Abnormal behaviour Diseases 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
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 101100377706 Escherichia phage T5 A2.2 gene Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000004298 cerebral vein Anatomy 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 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 1
- 238000004821 distillation Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 239000004531 microgranule Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- SBNFWQZLDJGRLK-UHFFFAOYSA-N phenothrin Chemical compound CC1(C)C(C=C(C)C)C1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 SBNFWQZLDJGRLK-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000003582 temporal bone Anatomy 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 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
- 229960002675 xylitol Drugs 0.000 description 1
- 210000000216 zygoma Anatomy 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a Chinese medicinal composition for treating cardiovascular and cerebrovascular diseases, which comprises 2.5-12.0% of tanshinone extract containing tanshinone 55-85%, 57.0-90.0% of total savianolic acid extract containing total savianolic acid 70-98%, 2.5-25.0% of panaxtriol saponins extract containing panaxtriol saponins 80-98%, and natural borneol or rosewood oil 2.5-15.0%. The composition has evident functions in resisting cerebral ischemia and myocardial ischemia, the curative effect is better than the application of single extract of tanshinone, total savianolic acid extract or panaxtriol saponins extract, thus providing a more effective and more convenient Chinese medicinal composition and preparation clinically.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof.
Background technology
According to China's Epidemiological study, though over nearly 50 years in the rural area or the city, the M ﹠ M of cardiovascular and cerebrovascular disease is all in rising trend.50～sixties, China's population cause of death central vessel disease and cerebrovascular occupied the five or six respectively, then rose to the two or three respectively later in 1975, and cardiovascular and cerebrovascular disease death person has accounted for first of whole disease cause of the death.China accounts for the percentage ratio of total dead population because of cardiovascular and cerebrovascular disease death person, rise to 42.6% of calendar year 2001 by 12.07% of nineteen fifty-seven, the person reaches 2,000,000 though die from the cardiovascular and cerebrovascular disease every year has the part patient to survive through rescue in addition, but majority stays deformity, can't take care of oneself, cause serious burden to relatives and society.Cardiovascular and cerebrovascular disease also is western countries crowd main causes of death.Infer that according to present existing epidemiologic data advancing of disease trend is: to the year two thousand twenty, the human diseases cause of the death puts in order will have great change, but coronary heart disease and apoplexy will be first and second of the human cause of the death.Till that time, estimate that global coronary heart disease death number will increase to 1,100 ten thousand from 6,300,000 of nineteen ninety; Apoplexy increases to 7,700,000 from 4,400,000.Blood circulation cause of the death formation will increase 59.6% in 30 years, and coronary heart disease and apoplexy increase 74.6% and 75% respectively.These data prove absolutely that cardiovascular and cerebrovascular disease is not only the principal disease of harm humans health, especially human " the No.1 killer " who causes death, disables at present and in following 20 years.
In the medicine of cardiovascular and cerebrovascular disease, the application of Chinese medicine and western medicine emphasizes particularly on different fields, and Chinese medicine also occupies the bigger market share with the little advantage of its side effect.In the Chinese patent medicine of present numerous treatment cardiovascular and cerebrovascular diseases, compound red sage root preparation occupies important position, is that the Chinese patent medicine of main active such as Radix Notoginseng total arasaponins, Radix Salviae Miltiorrhizae total phenolic acids, Radix Puerariae flavone, Herb Gynostemmae Pentaphylli total glycosides etc. also more and more is subject to people's attention in addition with effective site.The effect of the various effective ingredient in Chinese of treatment cardiovascular and cerebrovascular disease is had nothing in common with each other and is stressed, the great demand that has drug combination clinically, therefore, the compound red sage root preparation with the effective site preparation will have characteristics such as dosage is little, good effect, steady quality, broad market prospect.
Summary of the invention
The purpose of this invention is to provide the little Chinese medicine composition efficiently of a kind of amount.
Another object of the present invention provides the preparation method of said composition.
The present invention is implemented by following technical proposals.
Effective ingredient in Chinese compositions of the present invention comprises following component by weight percentage:
The tanshinone extract 2.5%～12.0% that contains 55%～85% TANSHINONES,
The Radix Salviae Miltiorrhizae total phenolic acids extract 57.0%～90.0% that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids,
The protoparaxotriol saporlirs extract 2.5%～25.0% that contains 80%～98% protoparaxotriol saporlirs,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 2.5%～15.0%.
Effective ingredient in Chinese compositions of the present invention is preferably and comprises following component by weight percentage:
The tanshinone extract 3.0%～8.0% that contains 55%～85% TANSHINONES,
The Radix Salviae Miltiorrhizae total phenolic acids extract 72.0%～82.0% that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids,
The protoparaxotriol saporlirs extract 6.0%～15.0% that contains 80%～98% protoparaxotriol saporlirs,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 4.0%～10.0%.
Effective ingredient in Chinese compositions of the present invention more preferably comprises following component by weight percentage:
The tanshinone extract 4% that contains 55%～85% TANSHINONES,
The Radix Salviae Miltiorrhizae total phenolic acids extract 76% that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids,
The protoparaxotriol saporlirs extract 13% that contains 80%～98% protoparaxotriol saporlirs,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 7%.
The above-mentioned tanshinone extract that contains 55%～85% TANSHINONES, available following method obtains:
(1) CO
2Extraction: the Radix Salviae Miltiorrhizae of getting after the pulverizing drops into CO
2Extraction kettle in the extraction equipment after system's each several part all reaches design temperature, boosts to setting pressure with extraction kettle. 75%～95% alcoholic solution is added system by the flow of setting, with CO
2Mix back circulation in whole system and carry out dynamic extraction; The condition of extraction is extracting pressure 15MPa～25Mpa, 30 ℃～55 ℃ of extraction and separation temperatures, and separation temperature is lower than extraction temperature, ethanol flow 0.5mL/min～1.5mL/min; After extraction is finished, emit extracting solution, concentrate, vacuum drying gets tanshinone extract, and its total tanshinone content is more than 55%.Medical material residue after the extraction is standby.
(2) ethanol extract from water precipitation: the Radix Salviae Miltiorrhizae of getting salvia piece or pulverizing, add 85～95% soak with ethanol 2 hours, then 65～85 ℃ of following reflux, extract, 3 times, each quantity of solvent is 5 times of crude drug weight, each 0.5～1.5 hour extraction time, the medical material residue after the extraction is standby; Merge extractive liquid,, extracting solution is being evaporated to 1/35～1/45 of original volume below 50 ℃, get concentrated solution; The water that adds 2～4 times of volumes in the concentrated solution was placed 6～24 hours, filtered; Filtrate gets tanshinone extract in dry below 50 ℃, and its total tanshinone content is more than 55%.
Get above-mentioned tanshinone extract, use an amount of dissolve with ethanol, join in the saturated hydroxypropyl solution, 25～50 ℃ stir after, restir 0.5～2 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.
The assay of total tanshinone (ultraviolet spectrophotometry) method is as follows in the above-mentioned tanshinone extract:
Instrument: Tianjin, island UV-250 spectrophotometer
The preparation of reference substance solution: get Tanshinone I I
A10mg is 1,2,4,6 with the methanol compound concentration, the standard solution of 8ug/ml.
The preparation of standard curve: with the reagent corresponding is the blank absorbance of measuring at 268nm wavelength place, is vertical coordinate with the absorbance, Tanshinone I I
AConcentration be abscissa, the drawing standard curve.
Algoscopy: get extract 20mg with methanol constant volume to 100ml, precision pipettes 5ml to 100ml standardize solution.Method working sample absorbance under the preparation of sighting target directrix curve calculates.
The above-mentioned preparation that contains the Radix Salviae Miltiorrhizae total phenolic acids extract of 70%～98% Radix Salviae Miltiorrhizae total phenolic acids, available following method obtains: get the medical material residue after the said extracted TANSHINONES, by the method preparation of embodiment one among Chinese patent application CN1459448A or the CN1384090A.Above-mentioned Radix Salviae Miltiorrhizae total phenolic acids assay and content of danshinolic acid B are measured referring to Chinese patent CN1600318A.
The above-mentioned protoparaxotriol saporlirs extract that contains 80%～98% protoparaxotriol saporlirs can obtain with following method: get the Radix Notoginseng of pulverizing, add water reflux, extract, or supersound extraction 2～3 times, amount of water is 5～7 times of medical material weight; Merge extractive liquid,, clear liquor or filtrate are got in centrifugal or filtration; Clear liquor or filtrate are gone up polyamide column, collect eluent; Macroporous adsorptive resins on the eluent, water elution liquid discards, and with 30～50% ethanol elutions, collects eluent, filters, and filtrate decompression concentrates, and drying promptly gets the protoparaxotriol saporlirs extract.Arasaponin R1 content is 10～20% in this protoparaxotriol saporlirs extract, and ginsenoside Re's content is 5%～15%, and the ginsenoside Rg1 is 60%～75%, and its notoginseng triol total saponin content is 80%～98%.
Above-mentioned macroporous resin is the macroporous resin of nonpolar or low pole, is preferably D101, AB-8 or ZTC type macroporous resin, and the best is an AB-8 type macroporous resin.
Above-mentioned protoparaxotriol saporlirs extractive content (in the ginsenoside Re) assay method is as follows:
1. instrument and reagent
1.1 instrument
Ultraviolet-uisible spectrophotometer.Chromatographic column.
1.2 standard substance, test sample and reagent
Standard substance: ginsenoside Re: Nat'l Pharmaceutical ﹠ Biological Products Control Institute
Test sample: protoparaxotriol saporlirs extract
Reagent: AB-8 macroporous resin or G..D.X-101 macroporous resin (60～80 orders, Tianjin chemical reagent two factories)
The ethanol analytical pure
Vanillin solution takes by weighing the 5g vanillin, and the ice acetic acid dissolving also is settled to 100ml.
The perchloric acid analytical pure
The glacial acetic acid analytical pure
Ginsenoside Re's standard solution: precision takes by weighing ginsenoside Re's standard substance 0.0100g, and with dissolve with methanol and be settled to 10ml, promptly every milliliter contains ginsenoside Re 1.0mg.
2. experiment
2.1 sample treatment: get 2mg protoparaxotriol saporlirs extract, with certain water gaging dilution (being diluted to about 50ml).
2.2 column chromatography: make the chromatography pipe with the 10mL syringe, interior dress 4cm AB-8 macroporous resin is washed post with 20mL95% ethanol earlier, discards eluent, and reuse 25mL washes post, discards eluent.The accurate sample solution of having handled well (seeing 2.1) that adds, flow speed control is about 1mL/min.Earlier wash post with 15mL, discard eluent, reuse 20mL95% ethanol elution arasaponin is collected eluent in evaporating dish, places 75 ℃ of water-baths to volatilize.Doing colour developing with this uses.
2.3 the preparation of blank sample: in clean evaporating dish, accurately add 0.2mL5% vanillin glacial acetic acid solution, rotate evaporating dish, residue is all dissolved, add 0.8mL perchloric acid again, move into behind the mixing in the 10mL band plug graduated centrifuge tube; Add the 0.2mL glacial acetic acid in the evaporating dish again, rotate evaporating dish, make the residual liquid dissolving, move into again in the above-mentioned centrifuge tube, heat 10min in 60 ℃ of water-baths, take out, after the ice bath cooling, accurately add glacial acetic acid 5.0mL, after shaking up, promptly get blank sample.
2.4 colour developing: in the above-mentioned evaporating dish that has volatilized, accurately add 0.2mL5% vanillin glacial acetic acid solution, rotate evaporating dish, residue is all dissolved, add 0.8mL perchloric acid again, move into behind the mixing in the 10mL band plug graduated centrifuge tube; Add the 0.2mL glacial acetic acid in the evaporating dish again, rotate evaporating dish, make the residual liquid dissolving, move into again in the above-mentioned centrifuge tube, heat 10min in 60 ℃ of water-baths, take out, after the ice bath cooling, accurately add glacial acetic acid 5.0mL, after shaking up, carry out colorimetric determination (after with blank sample ultraviolet-uisible spectrophotometer being returned zero, measuring again) with standard pipe in 560nm wavelength place with the 1cm colorimetric pool.
2.5 standard pipe: draw ginsenoside Re's standard solution (1.0mg/mL) 0.1mL, with certain water gaging dilution (about 10ml), below operation rises from " A2.2 column chromatography ... ", and is identical with sample, measures absorbance.
3 calculate:
C sample=(A1 * C mark * 100)/(A2 * 6)
In the formula:
C sample: the amount of Radix Notoginseng total glycosides (in the ginsenoside Re) in the extract, mg/100mL
A1: the absorbance of test solution,
A
2: the absorbance of titer,
C
Mark: the concentration of titer, mg/mL
Result of calculation keeps three position effective digitals.
Ginsenoside Re, arasaponin R1, ginsenoside Rg1's content assaying method is seen Chinese patent CN1600318A in the protoparaxotriol saporlirs extract of above-mentioned Radix Notoginseng total arasaponins more than 80%.
Natural Broneolum Syntheticum in the above-mentioned Chinese medicine composition should meet the Chinese Pharmacopoeia standard.Natural Broneolum Syntheticum can replace with the Borneolum Syntheticum that meets the Chinese Pharmacopoeia standard.
Lignum Dalbergiae Odoriferae oil in the above-mentioned Chinese medicine composition is that the Lignum Dalbergiae Odoriferae medical material is through the distillation gained.
Chinese medicine composition of the present invention, the various dosage forms that can be mixed and made into adjuvant on any or more than one pharmaceuticss such as starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol, glycine etc., for example, can be made into aqueous injection, tablet, slow releasing tablet, drop pill, granule, injectable powder, capsule, microgranule.Preferred dosage form is drop pill, injectable powder.
The preparation of Chinese medicine composition composition dropping pills of the present invention: get above-mentioned tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract and natural Broneolum Syntheticum (or Lignum Dalbergiae Odoriferae oil) to scale, Polyethylene Glycol-6000 or Polyethylene Glycol-4000 or both mixture mix homogeneously with 2～4 times of medicine gross weights, heating and melting, move in the dropping-pill machine jar after changing material, in medicine liquid droplet to 6～8 ℃ liquid paraffin or the methyl-silicone oil, oil removing, promptly.
The preparation of Chinese medicine composition injectable powder of the present invention: get above-mentioned tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract and natural Broneolum Syntheticum to scale, add an amount of adjuvant, the mixing postlyophilization, promptly.
Chinese medicine composition raw material sources of the present invention are easy to get, and are easy to industrialization; Can make various dosage forms as required, for clinical provide convenient, more effectively, the more controlled modern Chinese medicine of quality, for the patient brings more benefits, thereby produce the huge social benefit.
The present invention adopts the ferric chloride part to stick middle cerebral artery and causes the focal cerebral ischemia injury model, by mensuration, compared the treating cerebral ischemia of Chinese medicine composition of the present invention, tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract to rat model nervous symptoms and cerebral infarction scope.The result shows, Chinese medicine composition of the present invention has tangible treating cerebral ischemia, its curative effect is better than using separately tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, shows that effective ingredient in Chinese compositions of the present invention has stronger synergism.
Experimental example 1 several Chinese medicine extraction compositionss are to the influence of focal cerebral ischemia in rats
(1) experiment material
1, animal
The SD rat, male, body weight 180g～200g, the quality certification number: SCXK (capital) 2002-0003 is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..
2, medicine and reagent
Be subjected to reagent: the Chinese medicine composition of embodiment one, the Chinese medicine composition of embodiment two, the tanshinone extract of embodiment one, the Radix Salviae Miltiorrhizae total phenolic acids extract of embodiment one, the protoparaxotriol saporlirs extract of embodiment one.
Reagent: red tetrazolium (TTC) is pale yellow powder, Beijing Ma Shi fine chemicals company limited product, lot number: 011102.
3, instrument: XTT stero microscope, Yunnan Optical Instruments Factory's product; AEG-220 type electronic analytical balance, Japanese Shimadzu company product; The desk-top dentistry car of 307-6, Shanghai Dental Medical Apparatus and Instrument Factory's product; HZQ-C air bath agitator, Dongming, Harbin Medical Instruments factory product.
(2) experimental technique and result
1, grouping and administration
Laboratory animal is by the body weight random packet.Each treated animal is all in postoperative sublingual vein administration in 30 minutes, postoperative 2 hours and 23 hours intraperitoneal injection secondaries.Each medicine all is diluted to desired concn with normal saline, and injected dose adopts the 0.4ml/100g body weight.
2, the middle cerebral artery thrombus model is made
The anesthesia of rats by intraperitoneal injection 10% chloral hydrate solution (350mg/kg); right arm reclining is fixed; make a curved incision at paropia and external auditory meatus line mid point, be about 1.5cm, pinch off temporalis and excision; expose temporal bone; under stero microscope, at the bone window that cheekbone and the close oral-lateral 1mm place of temporo squamosum joint make a diameter 2.5mm, clear up residue with dental burr; expose middle cerebral artery (between tractus olfactorius and inferior cerebral vein), put small pieces plastic sheeting protection blood vessel surrounding tissue.Have the small pieces quantitative filter paper of 50% ferric chloride solution, 10 μ L to apply on this section middle cerebral artery suction, take off filter paper behind the 30min, use the normal saline flushing local organization, layer-by-layer suture steams again and raises.Room temperature is controlled at 24 ℃.
3, nervous symptoms standards of grading
To experimental animal 24h after surgery, carry out behavior and detect.Standards of grading: 1. carry the Mus tail and observe forelimb flexing situation, protract, be designated as 0 fen as two forelimb symmetries; As the offside forelimb of performing the operation shoulder flexing, elbow flexing, shoulder inward turning occur or has concurrently, is designated as 1 fen.2. animal is placed on the plane, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, be designated as 0 fen; As operation collateral resistance is descended, be designated as 1 fen.3. animal two forelimbs are put on the wire netting, observed muscular tension.Bilateral muscular tension equity and be 0 minute effectively; Operation offside muscle of anterior limb tension force descends and is designated as 1 fen.4. carry the Mus tail, animal has ceaselessly to operation offside revolver, is designated as 1 fen.According to above standard scoring, full marks are 4 minutes, and mark is high more, and the behavior disorder of animal is serious more.
4, the mensuration of cerebral infarction scope
Behind the animal via behavior scoring, broken end is got brain.The remainder that removes behind olfactory bulb, cerebellum and the low brain stem is cut into 5 crown below 4 ℃, and (every 5ml dye liquor contains 4%TTC 1.5ml, 1M K rapidly the brain sheet to be placed the TTC dye liquor
2HPO
40.1ml all the other adding distil waters are to scale), 37 ℃ of lucifuge temperature were incubated 30 minutes, took out to be placed on the 24h that keeps in Dark Place in 10% formalin.The non-ischemic region in dyed back is a rose, and infarct is a white.White organized carefully to dig down weigh, account for the percentage ratio of full brain weight and Ipsilateral brain weight as the cerebral infarction scope with blocking tissue's weight.
5, result
Above-mentioned experimental result represents with x ± s, and relatively t check between statistical test employing group the results are shown in Table 1 and table 2.
Several Chinese medicine extract of table 1 are to the influence of MCAO rat nervous symptoms (x ± s)
Annotate: compare * P＜0.05, * * P＜0.01 with model group; Compare with the tanshinone extract group,
#P＜0.05,
##P＜0.01; Compare with Radix Salviae Miltiorrhizae total phenolic acids extract group,
﹠amp;P＜0.05,
﹠amp; ﹠amp;P＜0.01; Compare with protoparaxotriol saporlirs extract group,
@P＜0.05,
@@P＜0.01
Several Chinese medicine extract of table 2 are to the influence of MCAO rat cerebral infarction scope (x ± s)
Annotate: compare * P＜0.05, * * P＜0.01 with model group; Compare with the tanshinone extract group,
#P＜0.05,
##P＜0.01; Compare with the Radix Salviae Miltiorrhizae total phenolic acids group,
﹠amp;P＜0.05,
﹠amp; ﹠amp;P＜0.01; Compare with protoparaxotriol saporlirs extract group,
@P＜0.05,
@@P＜0.01
The result of above table 1 and table 2 shows that each administration group all has tangible treating cerebral ischemia, and the curative effect of the present composition is best.
The present invention adopts rat experiment myocardial infarction model and external perfusion method, has compared the function of resisting myocardial ischemia of Chinese medicine composition of the present invention, tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract.The result shows that Chinese medicine composition of the present invention has tangible function of resisting myocardial ischemia, and its curative effect is better than using separately tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, shows that Chinese medicine composition of the present invention has stronger synergism.
The experimentation of experimental example 2 several Chinese medicine extract function of resisting myocardial ischemia
1, grouping and administration
70 of Wister male rats, body weight 250.8 ± 24.6 is divided into 7 groups at random by body weight: the normal saline matched group; The tanshinone extract group of embodiment two; The Radix Salviae Miltiorrhizae total phenolic acids extract group of experimental example two; The protoparaxotriol saporlirs extract group of experimental example two; The Chinese medicine composition of embodiment one; The Chinese medicine composition of embodiment two.Each medicine all is diluted to desired concn with normal saline, and dosage is 4ml/kg, the tail intravenously administrable.
2, method
(1), rat experiment myocardial infarction model: animal pentobarbital sodium intraperitoneal injection of anesthesia (45mg/kg), it is fixing to face upward the position.Tracheal intubation is made the longitudinal incision of 2cm in breastbone left side, nearly breastbone side is cut off the 3rd, the 4th and reined in cartilage, open the thoracic cavity after, connect artificial respirator (ventilation 2ml/100g, 50 times/min).Cut off pericardium, expose heart, left anterior descending coronary artery root threading is in order to ligation, and record standard II lead electrocardiogram was stablized 10 minutes, and the ligation left anterior descending coronary artery is closed the thoracic cavity.With syringe sucking-off animal throat secretions, make animal recover autonomous respiration.Behind the ligation coronary artery 15min, intravenously administrable.Behind the ligation coronary artery 4 hours, win heart, 5 of the following crosscuts of ligature, carry out chlorination nitro blue tetrazolium (NBT) dyeing, calculating myocardium infarcted region area accounts for the percentage ratio of ventricle and heart area, and carries out statistical procedures (t check).
(2), stripped langendorff heart perfusion: carry out with reference to the pharmacological experimental methodology third edition.
3, result
(1), to the influence of rat experiment myocardial inyaretion scope, the results are shown in Table 3.
The various extracts of table 3 are to the influence of rat experiment myocardial inyaretion scope (x ± s)
Annotate: compare * P＜0.05, * * P＜0.01 with model group; Compare with the tanshinone extract group,
#P＜0.05,
##P＜0.01; Compare with Radix Salviae Miltiorrhizae total phenolic acids extract group,
﹠amp;P＜0.05,
﹠amp; ﹠amp;P＜0.01; Compare with protoparaxotriol saporlirs extract group,
@P＜0.05,
@@P＜0.01
(2), to the influence of dirty coronary flow of guinea-pig heart and heart rate, the results are shown in Table 4.
The various extracts of table 4 are to the influence of dirty coronary flow of guinea-pig heart and heart rate (x ± s)
Annotate: compare * P＜0.05, * * P＜0.01 with the tanshinone extract group; Compare with Radix Salviae Miltiorrhizae total phenolic acids extract group,,
#P＜0.05,
##P＜0.01; Compare with protoparaxotriol saporlirs extract group,
﹠amp;P＜0.05,
﹠amp; ﹠amp;P＜0.01.
The result of above table 3 and table 4 shows that each administration group all has tangible function of resisting myocardial ischemia, and the curative effect of active component composition of the present invention is best.
The specific embodiment
To be easier to understand the present invention with reference to the following example, and provide embodiment and be in order to illustrate the present invention, rather than in order to limit the scope of the invention.
Embodiment one
Contain the preparation of the tanshinone extract of 55%～85% TANSHINONES: the Radix Salviae Miltiorrhizae of getting after the pulverizing drops into CO
2Extraction kettle in the extraction equipment after system's each several part all reaches design temperature, boosts to setting pressure with extraction kettle. 95% alcoholic solution is added system by the flow of setting, with CO
2Mix back circulation in whole system and carry out dynamic extraction; The condition of extraction is extracting pressure 20MPa, 45 ℃ of extraction temperature, 35 ℃ of separation temperatures, ethanol flow 1.0mL/min; After extraction is finished, emit extracting solution, concentrate, vacuum drying gets tanshinone extract, its total tanshinone content 64%.Medical material residue after the extraction is standby.
Contain the preparation of the Radix Salviae Miltiorrhizae total phenolic acids extract of 70%～98% Radix Salviae Miltiorrhizae total phenolic acids: get the medical material residue that extracts after the TANSHINONES, preparation method by embodiment one among the Chinese patent application CN1459448A obtains, its Radix Salviae Miltiorrhizae total phenolic acids content is 82.13%, and salvianolic acid B is 52.24%.
The preparation of protoparaxotriol saporlirs extract: get the Radix Notoginseng of pulverizing, add the water reflux, extract, 2 times, amount of water is 7 times of medical material weight, each 2 hours; Merge extractive liquid,, centrifugal, get clear liquor; Polyamide column on the clear liquor is collected eluent; AB-8 type macroporous resin on the eluent (production of Tianjin resin processing plant of Nankai University) post, water elution liquid discards, and with 40% ethanol elution of 4 times of amounts of medical material volume, collects eluent, filters, and filtrate decompression concentrates, and drying promptly gets the protoparaxotriol saporlirs extract.Arasaponin R1 content is 15.6% in this protoparaxotriol saporlirs extract, and ginsenoside Re's content is 8.7%, and ginsenoside Rg1's content is 63.1%, and its total saponin content is 91.2%.
Get the above-mentioned tanshinone extract 0.3g that contains 55%～85% TANSHINONES, above-mentioned Radix Salviae Miltiorrhizae total phenolic acids extract 5.3g, above-mentioned protoparaxotriol saporlirs extract 0.9g, the natural Broneolum Syntheticum 0.5g that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment two
Contain the preparation of the tanshinone extract of 55%～85% TANSHINONES: the Radix Salviae Miltiorrhizae of getting salvia piece or pulverizing, add 95% soak with ethanol 2 hours, 75 ℃ of following reflux, extract, 3 times, each quantity of solvent is 5 times of crude drug weight then, and extraction time was respectively 60 minutes, 30 minutes and 30 minutes; Merge extractive liquid,, extracting solution is being evaporated to 1/40 of original volume below 50 ℃, get concentrated solution; Add the water of 3 times of volumes in the concentrated solution, placed 12 hours, filter; Filtrate gets tanshinone extract, its total tanshinone content 61% in dry below 50 ℃.Medical material residue after the extraction is standby.
Contain the preparation of the Radix Salviae Miltiorrhizae total phenolic acids extract of 70%～98% Radix Salviae Miltiorrhizae total phenolic acids: get the medical material residue that extracts after the TANSHINONES, preparation method by embodiment one among the Chinese patent application CN1384090A obtains, its Radix Salviae Miltiorrhizae total phenolic acids content is 80.35%, and salvianolic acid B is 51.33%.
The preparation of protoparaxotriol saporlirs extract: get the Radix Notoginseng of pulverizing, add the water supersound extraction 2 times, amount of water is 6.5 times of medical material weight, each 30 minutes; Merge extractive liquid, filters; Polyamide column on the filtrate is collected eluent; D101 type macroporous resin on the eluent (production of Tianjin resin processing plant of Nankai University) post, water elution liquid discards, and with 45% ethanol elution of 4.5 times of amounts of medical material volume, collects eluent, filters, and filtrate decompression concentrates, and drying promptly gets the protoparaxotriol saporlirs extract.Arasaponin R1 content is 15.8% in this protoparaxotriol saporlirs extract, and ginsenoside Re's content is 8.3%, and ginsenoside Rg1's content is 62.9%, and its total saponin content is 91.8%.
Get the above-mentioned tanshinone extract 0.3g that contains 55%～85% TANSHINONES, above-mentioned Radix Salviae Miltiorrhizae total phenolic acids extract 5.3g, above-mentioned protoparaxotriol saporlirs extract 0.9g, the Lignum Dalbergiae Odoriferae oil 0.5g that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids, add 9.0g Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment three
Contain the preparation of the tanshinone extract of 55%～85% TANSHINONES: the Radix Salviae Miltiorrhizae of getting after the pulverizing drops into CO
2Extraction kettle in the extraction equipment after system's each several part all reaches design temperature, boosts to setting pressure with extraction kettle. 90% alcoholic solution is added system by the flow of setting, with CO
2Mix back circulation in whole system and carry out dynamic extraction; The condition of extraction is extracting pressure 250MPa, 45 ℃ of extraction temperature, 35 ℃ of separation temperatures, ethanol flow 0.8mL/min; After extraction is finished, emit extracting solution, concentrate, vacuum drying gets tanshinone extract, its total tanshinone content 59%.Medical material residue after the extraction is standby.
Contain the preparation of the Radix Salviae Miltiorrhizae total phenolic acids extract of 70%～98% Radix Salviae Miltiorrhizae total phenolic acids: get the medical material residue that extracts after the TANSHINONES, preparation method by embodiment one among the Chinese patent application CN1459448A obtains, its Radix Salviae Miltiorrhizae total phenolic acids content is 81.97%, and salvianolic acid B is 52.56%.
The preparation of protoparaxotriol saporlirs extract: get the Radix Notoginseng of pulverizing, add the water reflux, extract, 3 times, amount of water is 6 times of medical material weight, each 1.5 hours; Merge extractive liquid,, centrifugal, get clear liquor; Polyamide column on the clear liquor is collected eluent; AB-8 type macroporous resin on the eluent (production of Tianjin resin processing plant of Nankai University) post, water elution liquid discards, and with 37% ethanol elution of 4 times of amounts of medical material volume, collects eluent, filters, and filtrate decompression concentrates, and drying promptly gets the protoparaxotriol saporlirs extract.Arasaponin R1 content is 14.2% in this protoparaxotriol saporlirs extract, and ginsenoside Re's content is 8.1%, and ginsenoside Rg1's content is 62.7%, and its total saponin content is 91.3%.
Get the above-mentioned tanshinone extract 0.3g that contains 55%～85% TANSHINONES, above-mentioned Radix Salviae Miltiorrhizae total phenolic acids extract 6.6g, above-mentioned protoparaxotriol saporlirs extract 0.8g, the natural Broneolum Syntheticum 0.5g that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment four
Get the tanshinone extract 0.4g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 1.0g, the natural Broneolum Syntheticum 0.4g of the Radix Salviae Miltiorrhizae total phenolic acids extract 5.3g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment five
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 0.8g, the natural Broneolum Syntheticum 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 4.8g, the embodiment three that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment six
Get the tanshinone extract 0.4g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 0.8g, the Lignum Dalbergiae Odoriferae oil 0.4g of the Radix Salviae Miltiorrhizae total phenolic acids extract 8.5g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one, add 12.0g Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment seven
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 0.9g, the natural Broneolum Syntheticum 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 5.3g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and 18.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment eight
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment two, protoparaxotriol saporlirs extract 0.8g, the natural Broneolum Syntheticum 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 5.9g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment two; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and 18.0g Polyethylene Glycol-4000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment nine
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment three, protoparaxotriol saporlirs extract 1.0g, the natural Broneolum Syntheticum 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 4.9g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment three; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and 19.0g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ methyl-silicone oil of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment ten
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 0.9g, the natural Broneolum Syntheticum 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 6.5g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and 3.5g Polyethylene Glycol-4000 and 14.0g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 11
Get the tanshinone extract 0.4g that contains 55%～85% TANSHINONES of embodiment three, protoparaxotriol saporlirs extract 0.8g, the natural Broneolum Syntheticum 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 7.5g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment three; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder art of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and 16.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 12
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment three, protoparaxotriol saporlirs extract 0.8g, the Borneolum Syntheticum 0.4g of the Radix Salviae Miltiorrhizae total phenolic acids extract 5.7g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment three; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and 18.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 13
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 0.9g, the Lignum Dalbergiae Odoriferae oil 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 5.3g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl beta cyclodextrin.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, Lignum Dalbergiae Odoriferae oil and 18.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ methyl-silicone oil of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 14
Get the tanshinone extract 0.3g that contains 55%～85% TANSHINONES of embodiment two, protoparaxotriol saporlirs extract 0.8g, the Lignum Dalbergiae Odoriferae oil 0.5g of the Radix Salviae Miltiorrhizae total phenolic acids extract 5.9g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment two; An amount of dissolve with ethanol of tanshinone extract, Lignum Dalbergiae Odoriferae oil joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract, Lignum Dalbergiae Odoriferae oil and hydroxypropyl.Above-mentioned clathrate powder and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract and 3.5g Polyethylene Glycol-4000 and 14.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 15
Get the tanshinone extract 0.8g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 2.5g, the natural Broneolum Syntheticum 1.2g of the Radix Salviae Miltiorrhizae total phenolic acids extract 15.4g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and mannitol 5.5g, calcium disodium edetate 0.9g and distilled water 1ml, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 16
Get the tanshinone extract 0.8g that contains 55%～85% TANSHINONES of embodiment two, protoparaxotriol saporlirs extract 2.9g, the natural Broneolum Syntheticum 1.2g of the Radix Salviae Miltiorrhizae total phenolic acids extract 14.7g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment two; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and low molecular dextran 5.5g, calcium disodium edetate 0.9g and distilled water 1ml, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 17
Get the tanshinone extract 0.9g that contains 55%～85% TANSHINONES of embodiment three, protoparaxotriol saporlirs extract 1.9g, the Borneolum Syntheticum 1.2g of the Radix Salviae Miltiorrhizae total phenolic acids extract 15.6g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment three; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and glucose 5.5g, sodium thiosulfate 0.9g and distilled water 1ml, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 18
Get the tanshinone extract 0.8g that contains 55%～85% TANSHINONES, the Lignum Dalbergiae Odoriferae oil 1.5g of embodiment one, join in the saturated hydroxypropyl solution of 13ml, stirring and dissolving filters, the filtrate cold drying, the clathrate powder of tanshinone extract, Lignum Dalbergiae Odoriferae oil and hydroxypropyl.Except that above-mentioned clathrate powder, get protoparaxotriol saporlirs extract 2.5g, mannitol 5.5g, calcium disodium edetate 0.9g and the distilled water 2ml of the Radix Salviae Miltiorrhizae total phenolic acids extract 15.6g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one again, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 19
Get the tanshinone extract 0.6g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 1.2g, the Borneolum Syntheticum 0.8g of the Radix Salviae Miltiorrhizae total phenolic acids extract 11.7g, the embodiment one that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and 210g microcrystalline Cellulose mix homogeneously, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate adds the 24g Pulvis Talci, mixing, fill in 1000 capsules, promptly.
Embodiment 20
Get the tanshinone extract 0.6g that contains 55%～85% TANSHINONES of embodiment one, protoparaxotriol saporlirs extract 1.2g, the natural Broneolum Syntheticum 0.8g of the Radix Salviae Miltiorrhizae total phenolic acids extract 11.7g, the embodiment two that contain 70%～98% Radix Salviae Miltiorrhizae total phenolic acids of embodiment one; An amount of dissolve with ethanol of tanshinone extract joins in the saturated hydroxypropyl solution, after stirring, restir 1 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.The clathrate powder of tanshinone extract and hydroxypropyl and Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract, natural Broneolum Syntheticum and with 64g microcrystalline Cellulose and 20g magnesium stearate mix homogeneously, be pressed into 1000, promptly.
Claims (8)
1. Chinese medicine composition for the treatment of cardiovascular and cerebrovascular disease, form by following component by weight percentage:
The tanshinone extract 2.5%～12.0% that contains 55%～85% TANSHINONES,
The Radix Salviae Miltiorrhizae total phenolic acids extract 57.0%～90.0% that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids,
The protoparaxotriol saporlirs extract 2.5%～25.0% that contains 80%～98% protoparaxotriol saporlirs,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 2.5%～15.0%;
Described protoparaxotriol saporlirs extract is prepared by following method: get the Radix Notoginseng of pulverizing, add water reflux, extract, or supersound extraction 2～3 times, amount of water is 5～7 times of medical material weight; Merge extractive liquid,, clear liquor or filtrate are got in centrifugal or filtration; Clear liquor or filtrate are gone up polyamide column, collect eluent; Macroporous adsorptive resins on the eluent, water elution liquid discards, and with 30～50% ethanol elutions, collects eluent, filters, and filtrate decompression concentrates, drying, promptly;
Described macroporous resin is D101, AB-8 or ZTC type macroporous resin.
2. according to the described Chinese medicine composition of claim 1, it is characterized in that the percentage by weight of described each component is:
The tanshinone extract 3.0%～8.0% that contains 55%～85% TANSHINONES,
The Radix Salviae Miltiorrhizae total phenolic acids extract 72.0%～82.0% that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids,
The protoparaxotriol saporlirs extract 6.0%～15.0% that contains 80%～98% protoparaxotriol saporlirs,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 4.0%～10.0%.
3. according to the described Chinese medicine composition of claim 1, it is characterized in that the percentage by weight of described each component is:
The tanshinone extract 4% that contains 55%～85% TANSHINONES,
The Radix Salviae Miltiorrhizae total phenolic acids extract 76% that contains 70%～98% Radix Salviae Miltiorrhizae total phenolic acids,
The protoparaxotriol saporlirs extract 13% that contains 80%～98% protoparaxotriol saporlirs,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 7%.
4. according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that, with the alternative described tanshinone extract that contains 55%～85% TANSHINONES of the clathrate of tanshinone extract and hydroxypropyl; The clathrate of described tanshinone extract and hydroxypropyl prepares with following method: the weighting profit requires the tanshinone extract that contains 55%～85% TANSHINONES of predetermined weight percentage ratio, use an amount of dissolve with ethanol, join in the saturated hydroxypropyl solution, 25～50 ℃ stir after, restir 0.5～2 hour, cold preservation is spent the night, sucking filtration, the filtrate cold drying, the clathrate powder of tanshinone extract and hydroxypropyl.
5. according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that described tanshinone extract is prepared by following method: the Radix Salviae Miltiorrhizae of getting after the pulverizing drops into CO
2Extraction kettle in the extraction equipment after system's each several part all reaches design temperature, boosts to setting pressure with extraction kettle, 75%～95% alcoholic solution is added system by the flow of setting, with CO
2Mix back circulation in whole system and carry out dynamic extraction; The condition of extraction is extracting pressure 15Mpa～25Mpa, 30 ℃～55 ℃ of extraction and separation temperatures, and separation temperature is lower than extraction temperature, ethanol flow 0.5mL/min～1.5mL/min; After extraction is finished, emit extracting solution, concentrate, vacuum drying gets tanshinone extract.
6. according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that, described tanshinone extract is prepared by following method: the Radix Salviae Miltiorrhizae of getting salvia piece or pulverizing, add 85～95% soak with ethanol 2 hours, then 65～85 ℃ of following reflux, extract, 3 times, each quantity of solvent is 5 times of crude drug weight, each 0.5～1.5 hour extraction time; Merge extractive liquid,, extracting solution is being evaporated to 1/35～1/45 of original volume below 50 ℃, get concentrated solution; The water that adds 2～4 times of volumes in the concentrated solution was placed 6～24 hours, filtered; Filtrate gets tanshinone extract in dry below 50 ℃.
7. be the drop pill that active component is made according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that, described drop pill is prepared from by following method: get above-mentioned tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acids extract, protoparaxotriol saporlirs extract and natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil to scale, Polyethylene Glycol-6000 or Polyethylene Glycol-4000 or both mixture mix homogeneously with 2～4 times of medicine gross weights, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing, promptly.
8. be the injectable powder that active component is made according to the described Chinese medicine composition of the arbitrary claim of claim 1～3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005100148391A CN1919240B (en) | 2005-08-24 | 2005-08-24 | Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005100148391A CN1919240B (en) | 2005-08-24 | 2005-08-24 | Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1919240A CN1919240A (en) | 2007-02-28 |
| CN1919240B true CN1919240B (en) | 2011-02-16 |
Family
ID=37777176
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2005100148391A Expired - Fee Related CN1919240B (en) | 2005-08-24 | 2005-08-24 | Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1919240B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050037094A1 (en) | 2003-07-31 | 2005-02-17 | Xijun Yan | Composition for heart disease, its active ingredients, method to prepare same and uses thereof |
| CN102028745B (en) * | 2009-09-29 | 2013-12-11 | 天津天士力现代中药资源有限公司 | Drug for treating coronary heart disease and preparation process |
| CN102028744B (en) * | 2009-09-29 | 2013-12-11 | 天津天士力现代中药资源有限公司 | Drug for treating coronary heart disease and preparation method |
| CN102028737B (en) * | 2009-09-29 | 2013-12-11 | 天津天士力现代中药资源有限公司 | Drug for treating coronary heart disease |
| CN102028738B (en) * | 2009-09-29 | 2013-12-11 | 天津天士力现代中药资源有限公司 | Medicament for treating coronary heart disease and preparation thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1419124A (en) * | 2002-12-23 | 2003-05-21 | 北京采瑞医药有限公司 | Method for controlling quality of compound red sage root preparation used for treating cardio-cerebral vascualr disease |
| CN1424112A (en) * | 2002-12-17 | 2003-06-18 | 上海医药工业研究院 | Water soluble dressing for insoluble medicines and preparation thereof |
| CN1459448A (en) * | 2002-05-23 | 2003-12-03 | 天津天士力制药股份有限公司 | Preparation method of red sageroot total phenolic acid and its use |
| CN1600318A (en) * | 2003-09-23 | 2005-03-30 | 天津天士力制药股份有限公司 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
-
2005
- 2005-08-24 CN CN2005100148391A patent/CN1919240B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1459448A (en) * | 2002-05-23 | 2003-12-03 | 天津天士力制药股份有限公司 | Preparation method of red sageroot total phenolic acid and its use |
| CN1424112A (en) * | 2002-12-17 | 2003-06-18 | 上海医药工业研究院 | Water soluble dressing for insoluble medicines and preparation thereof |
| CN1419124A (en) * | 2002-12-23 | 2003-05-21 | 北京采瑞医药有限公司 | Method for controlling quality of compound red sage root preparation used for treating cardio-cerebral vascualr disease |
| CN1600318A (en) * | 2003-09-23 | 2005-03-30 | 天津天士力制药股份有限公司 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
Non-Patent Citations (4)
| Title |
|---|
| 张山苗，陈俊秀.三七几种成分对血小板聚集功能及其cAMP含量的研究.中山医学院学报5 1.1984,5(1),75. |
| 张山苗,陈俊秀.三七几种成分对血小板聚集功能及其cAMP含量的研究.中山医学院学报5 1.1984,5(1),75. * |
| 赵瑜等.大孔吸附树脂分离纯化人参二醇类和三醇类皂甙.天然产物研究与开发16 3.2004,16(3),236～237. |
| 赵瑜等.大孔吸附树脂分离纯化人参二醇类和三醇类皂甙.天然产物研究与开发16 3.2004,16(3),236～237. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1919240A (en) | 2007-02-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100404035C (en) | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease | |
| JP4943846B2 (en) | Pharmaceutical compositions for the treatment of cardiovascular and cerebrovascular diseases | |
| CN1919248B (en) | Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease | |
| CN1919240B (en) | Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases | |
| CN1919239B (en) | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases | |
| CN1919252B (en) | Medicine for treating cardiovascular and cerebrovascular disease | |
| CN1919247B (en) | Chinese medicine for treating cardiovascular and cerebrovascular disease | |
| CN1919238B (en) | Medicine for treating cardiovascular and cerebrovascular disease | |
| CN1919237B (en) | Medicine for treating cardiovascular and cerebrovascular diseases | |
| CN1919242B (en) | Traditional Chinese medicine composition for treating cardiac and cerebral vascular disease | |
| CN1919249B (en) | Chinese traditional medicine for treating cardiovascular and cerebrovascular disease | |
| CN1919235B (en) | Cardiac and cerebral vascular disease treating pharmaceutical composition | |
| CN100467025C (en) | Use of asiaticoside in preparation of medicines for diseases of cardio-cerebral blood vessels | |
| CN1919236B (en) | Medicine for treating cardiovascular and cerebrovascular diseases | |
| CN100509009C (en) | A Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and ischemic apoplexy, and its preparation method | |
| CN1919244B (en) | Chinese traditional medicine for treating cardiovascular disease | |
| CN1919241B (en) | Chinese medicinal preparation for treating cardiovascular and cerebrovascular disease | |
| CN1919253B (en) | Cardiac and cerebral vascular disease treating medicinal composition | |
| CN1919251B (en) | Traditional Chinese medicine composition for treating cardiac vascular disease | |
| CN1919243B (en) | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases | |
| CN1919250B (en) | Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease | |
| CN1582946B (en) | Use of centellosic acid derivative in preparation of medicines for diseases of cardio-cerebral blood vessels | |
| CN104277083B (en) | A kind of luteolin -7-o- β-D-Glucose aldehydic acid glycosides Preparation method and use | |
| CN1919246B (en) | Traditional Chinese medicine for treating cardiovascular diseases | |
| CN1919245B (en) | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20070608 Address after: Tianjin City Hedong District of Beichen Puji No. 2 in the modern Chinese medicine city Applicant after: Tianjin Tianshili Pharmaceutical Co., Ltd. Address before: The white road of Beichen science and Technology Park in Beichen District of Tianjin City Xinyi Liaohe Road No. 1 Applicant before: Tianshili Modern Traditional Chinese Medicine Research & Devleopment Co., Ltd., |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: TASLY PHARMACEUTICAL GROUP CO., LTD. Free format text: FORMER NAME: TIANJIN TASLY PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 300402 Tianjin city Beichen District Puji Hedong No. 2 in the modern Chinese medicine city Patentee after: Tasly Pharmaceutical Group Co., Ltd. Address before: 300402 Tianjin city Beichen District Puji Hedong No. 2 in the modern Chinese medicine city Patentee before: Tianjin Tianshili Pharmaceutical Co., Ltd. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 300402 Tianjin city Beichen District Puji Hedong No. 2 in the modern Chinese medicine city Patentee after: Tasly Pharmaceutical Group Limited by Share Ltd Address before: 300402 Tianjin city Beichen District Puji Hedong No. 2 in the modern Chinese medicine city Patentee before: Tasly Pharmaceutical Group Co., Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110216 Termination date: 20190824 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |