CN1462750A - Erigeron ester B and its preparation method as well as application in pharmacy - Google Patents
Erigeron ester B and its preparation method as well as application in pharmacy Download PDFInfo
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- CN1462750A CN1462750A CN 03117753 CN03117753A CN1462750A CN 1462750 A CN1462750 A CN 1462750A CN 03117753 CN03117753 CN 03117753 CN 03117753 A CN03117753 A CN 03117753A CN 1462750 A CN1462750 A CN 1462750A
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- erigeroster
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- erigeron
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- 238000002360 preparation method Methods 0.000 title claims description 16
- 150000002148 esters Chemical class 0.000 title description 6
- 241000132521 Erigeron Species 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 8
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 8
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000000284 extract Substances 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 239000003560 cancer drug Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 241001013934 Erigeron breviscapus Species 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- -1 caffeic acid ester compound Chemical class 0.000 abstract description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 abstract description 3
- 241000208838 Asteraceae Species 0.000 abstract description 2
- 241000196324 Embryophyta Species 0.000 abstract description 2
- 230000003064 anti-oxidating effect Effects 0.000 abstract 1
- 230000000702 anti-platelet effect Effects 0.000 abstract 1
- 239000003146 anticoagulant agent Substances 0.000 abstract 1
- 210000004204 blood vessel Anatomy 0.000 abstract 1
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- DJSISFGPUUYILV-ZFORQUDYSA-N scutellarin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC(O)=CC=1)O2 DJSISFGPUUYILV-ZFORQUDYSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DJSISFGPUUYILV-UHFFFAOYSA-N UNPD161792 Natural products O1C(C(O)=O)C(O)C(O)C(O)C1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC(O)=CC=1)O2 DJSISFGPUUYILV-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 230000002776 aggregation Effects 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
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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- NPLTVGMLNDMOQE-UHFFFAOYSA-N carthamidin Natural products C1=CC(O)=CC=C1C1OC2=CC(O)=C(O)C(O)=C2C(=O)C1 NPLTVGMLNDMOQE-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
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- UFCLZKMFXSILNL-AALYGJCLSA-N 3,4-Dicaffeoylquinic acid Natural products O=C(O[C@@H]1[C@H](OC(=O)/C=C/c2cc(O)c(O)cc2)C[C@](O)(C(=O)O)C[C@@H]1O)/C=C/c1cc(O)c(O)cc1 UFCLZKMFXSILNL-AALYGJCLSA-N 0.000 description 2
- UFCLZKMFXSILNL-BKUKFAEQSA-N 3,4-di-O-caffeoylquinic acid Natural products O[C@H]1C[C@](O)(C[C@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1OC(=O)C=Cc3ccc(O)c(O)c3)C(=O)O UFCLZKMFXSILNL-BKUKFAEQSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFCLZKMFXSILNL-PSEXTPKNSA-N Isochlorogenic acid b Chemical compound O([C@@H]1C[C@@](O)(C[C@H]([C@H]1OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)O)C(O)=O)C(=O)\C=C\C1=CC=C(O)C(O)=C1 UFCLZKMFXSILNL-PSEXTPKNSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
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- 238000000338 in vitro Methods 0.000 description 2
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- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- KRZBCHWVBQOTNZ-PSEXTPKNSA-N 3,5-di-O-caffeoyl quinic acid Chemical compound O([C@@H]1C[C@](O)(C[C@H]([C@@H]1O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C(O)=O)C(=O)\C=C\C1=CC=C(O)C(O)=C1 KRZBCHWVBQOTNZ-PSEXTPKNSA-N 0.000 description 1
- MVCIFQBXXSMTQD-UHFFFAOYSA-N 3,5-dicaffeoylquinic acid Natural products Cc1ccc(C=CC(=O)OC2CC(O)(CC(OC(=O)C=Cc3ccc(O)c(O)c3)C2O)C(=O)O)cc1C MVCIFQBXXSMTQD-UHFFFAOYSA-N 0.000 description 1
- CWVRJTMFETXNAD-GMZLATJGSA-N 5-Caffeoyl quinic acid Natural products O[C@H]1C[C@](O)(C[C@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-GMZLATJGSA-N 0.000 description 1
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 1
- YDDUMTOHNYZQPO-RVXRWRFUSA-N Cynarine Chemical compound O([C@@H]1C[C@@](C[C@H]([C@@H]1O)O)(OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C(O)=O)C(=O)\C=C\C1=CC=C(O)C(O)=C1 YDDUMTOHNYZQPO-RVXRWRFUSA-N 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
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- 210000000709 aorta Anatomy 0.000 description 1
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 1
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 1
- 229940117893 apigenin Drugs 0.000 description 1
- 235000008714 apigenin Nutrition 0.000 description 1
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- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
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- 210000004185 liver Anatomy 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- HZZOEADXZLYIHG-UHFFFAOYSA-N magnesiomagnesium Chemical compound [Mg][Mg] HZZOEADXZLYIHG-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
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- 238000009210 therapy by ultrasound Methods 0.000 description 1
- CWVRJTMFETXNAD-NXLLHMKUSA-N trans-5-O-caffeoyl-D-quinic acid Chemical compound O[C@H]1[C@H](O)C[C@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-NXLLHMKUSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明涉及结构式(I)的新咖啡酸酯类化合物飞蓬酯乙，它可以菊科飞蓬属植物灯盏细辛Erigeron breviscapus(Vant.)Hand.－Mazz.的干燥全草中提取分离得到。化合物(I)具有抗血小板聚集、抗氧化和扩张血管活性，可作为治疗心脑血管疾病药物。
The invention relates to a new caffeic acid ester compound of the structural formula (I), which can be obtained by extracting and separating the dried whole herb of Erigeron breviscapus (Vant.) Hand.-Mazz., a plant of the genus Asteraceae. The compound (I) has anti-platelet aggregation, anti-oxidation and blood vessel expansion activities, and can be used as a drug for treating cardiovascular and cerebrovascular diseases.
Description
1、技术领域1. Technical field
本发明涉及一种具有治疗心脑血管疾病活性的新化合物飞蓬酯乙(Erigeroster B)，具体地说是从灯盏细辛中提取的新化合物飞蓬酯乙(Erigeroster B)、制备方法及在制药中的应用。The present invention relates to a new compound Erigeroster B which has the activity of treating cardiovascular and cerebrovascular diseases, specifically the new compound Erigeroster B extracted from Erigeron breviscapus, its preparation method and its application in pharmaceuticals Applications.
2、背景技术2. Background technology
心脑血管疾病日益增多，其病情严重，是人类病死的第一原因，因而其发病与治疗也受到医药界和社会的格外关注。加以经济发展，人口老龄化，老年人的心脑血管疾病又多，使问题更尖锐。灯盏细辛又名灯盏花，系菊科飞蓬属植物短葶飞蓬Erigeron breviscapus(Vant.)Hand.-Mazz.的干燥全草，具有散寒解表，祛风除湿，活络止痛的功效。云南药物研究所张人伟等首次从灯盏细辛中分离到黄酮类活性成分灯盏乙素，并把灯盏花乙素为主、含少量灯盏甲素(芹菜素苷)的混合物称为灯盏花素(breviscapin)[张人伟，杨生元，林永月，药学学报(1981)，16(1)，68-6]。除了灯盏乙素外，专利CN1136434公开了二咖啡酸奎宁酸酯类化合物3，5-二咖啡酰基奎宁酸和3，4-二咖啡酰基奎宁酸(3，4-dicaffeoyl quinic acid)]。CN1064236C则公开了焦袂康酸(promenonic acid)及飞蓬苷(erigenoide)在治疗心脑血管疾病方面应用。张卫东等申请了从灯盏细辛中分离到的活性成分1-(2’-γ-吡喃酮)-6-咖啡酰基-β-D-葡萄糖苷的制剂和制备方法的专利CN1252276。以上公开的是已知化合物新用途的专利，没有新化合物专利。The number of cardiovascular and cerebrovascular diseases is increasing day by day, and its serious condition is the first cause of human death. Therefore, its incidence and treatment have also received special attention from the medical community and society. In addition to economic development, the population is aging, and there are many cardiovascular and cerebrovascular diseases in the elderly, which makes the problem more acute. Erigeron breviscapus, also known as Erigeron breviscapus, is the dry whole plant of Erigeron breviscapus (Vant.) Hand.-Mazz. in the genus Asteraceae. For the first time, Zhang Renwei from the Yunnan Institute of Materia Medica isolated scutellarin, an active ingredient of flavonoids, from breviscapine, and called the mixture of scutellarin-based and a small amount of breviscapin (apigenin) called breviscapin (breviscapin). )[Zhang Renwei, Yang Shengyuan, Lin Yongyue, Acta Pharmaceutical Sinica (1981), 16(1), 68-6]. In addition to scutellarin, patent CN1136434 discloses dicaffeoyl quinic acid ester compounds 3,5-dicaffeoyl quinic acid and 3,4-dicaffeoyl quinic acid (3,4-dicaffeoyl quinic acid)] . CN1064236C discloses the application of promenonic acid and erigenoide in the treatment of cardiovascular and cerebrovascular diseases. Zhang Weidong et al. applied for the patent CN1252276 on the preparation and preparation method of the active ingredient 1-(2'-γ-pyrone)-6-caffeoyl-β-D-glucoside isolated from Erigeron breviscapus. The above disclosures are patents for new uses of known compounds, and there are no patents for new compounds.
3、发明内容：3. Contents of the invention:
本发明针对现有技术的空白，本发明公开新活性成分飞蓬酯乙，本发明The present invention is aimed at the blank of the prior art, and the present invention discloses new active ingredient phenanthryl ester B, and the present invention
提供了如下技术方案：The following technical solutions are provided:
具有如下的结构式化合物飞蓬酯乙：
Erigoster BErigoster B
飞蓬酯乙
本发明提供了制备权利要求1的化合物的方法，取灯盏细辛(Erigeronbrevicapus)的全草或地上部分，粉碎，用0-95％乙醇水溶液或丙酮水溶液提取三次，合并三次提取液，减压浓缩。浓缩液上大孔树脂层析，先用水洗脱，再用40％，收集40％乙醇洗脱液后减压浓缩，此部分用Sephdex HL-20反复纯化便飞蓬酯乙(Erigeroster B)。The present invention provides a method for preparing the compound of claim 1. Take the whole herb or aerial parts of Erigeron brevicapus, pulverize, extract three times with 0-95% ethanol aqueous solution or acetone aqueous solution, combine the three extracts, and concentrate under reduced pressure . The concentrated solution was subjected to macroporous resin chromatography, firstly eluted with water, then with 40% ethanol, and then concentrated under reduced pressure after collecting the 40% ethanol eluate. This part was repeatedly purified with Sephdex HL-20 to obtain Erigeroster B (Erigeroster B).
本发明还提供了含化合物飞蓬酯乙(Erigeroster B)作为活性成分的治疗心脑血管疾病的药用组合物。The invention also provides a pharmaceutical composition for treating cardiovascular and cerebrovascular diseases containing the compound Erigeroster B as an active ingredient.
本发明同时提供了化合物飞蓬酯乙(Erigeroster B)在制备预防或治疗癌症药物中的应用。The present invention also provides the application of the compound Erigeroster B in the preparation of drugs for preventing or treating cancer.
化合物结构数据如下：分子式，C26H24O13，分子量，544.46，[α]D，+37.14°(0.00175，丙酮)；IR(KBr压片)：2970.57-3645.31，1694.68，1632.87，1520.46，1605.84，1283.57，1162.82cm-1；UVλmax(MeOH)：330(22018)，302(14620)，244(5966)，218(12267)nm；1HNMR(500Hz，pyridine-d5，ppm，J in Hz)：2.84-2.93(2H，m，H-2α，H-2β)，6.03(1H，t，5.1，H-3)，4.72(1H，t，5.1，H-4)，4.93(1H，t，4.3，H-5)，5.07(1H，m，H-6)，5.17(1H，dd，12.3，2.7，H-9a)，6.04(1H，dd，8.8，12.3，H-9b).6.60，7.14(each 1H，d，15.8，H-2’，H-2”)，8.09，8.06(each 1H，d，15.8，H-3’，H-3”)，7.31，7.31(each 1H，dd，8.0，1.5，H-5’，H-5”)，7.18，7.18(each 1H，d，8.0，H-6’，H-6”)，7.80，7.56(each 1H，brs，H-9’，H-9”)。13CNMR(100.62Hz，pyridine-d5，ppm)：104.82(C-1)，38.24(C-2)，67.49(C-3)，67.40(C-4)，78.01(C-5)，80.45(C-6)，64.18(C-9)，170.97(C-10)，167.95，167.77(C-1’，C-1”)，115.97，115.23(C-2’，C-2”)，146.25，146.21(C-3’，C-3”)，127.51，127.28(C-4’，C-4”)，122.57，122.31(C-5’，C-5”)，116.84，116.79(C-6’，C-6”)，150.37，150.186(C-7’，C-7”)，147.62，147.59(C-8’，C-8”)，116.13，115.89(C-9’，C-9”)。The structural data of the compound are as follows: molecular formula, C 26 H 24 O 13 , molecular weight, 544.46, [α] D , +37.14° (0.00175, acetone); IR (KBr tablet): 2970.57-3645.31, 1694.68, 1632.87, 1520.46, 1605.84 , 1283.57, 1162.82cm -1 ; UVλ max (MeOH): 330(22018), 302(14620), 244(5966), 218(12267)nm; 1 HNMR(500Hz, pyridine-d 5 , ppm, J in Hz ): 2.84-2.93 (2H, m, H-2α, H-2β), 6.03 (1H, t, 5.1, H-3), 4.72 (1H, t, 5.1, H-4), 4.93 (1H, t , 4.3, H-5), 5.07 (1H, m, H-6), 5.17 (1H, dd, 12.3, 2.7, H-9a), 6.04 (1H, dd, 8.8, 12.3, H-9b).6.60 , 7.14 (each 1H, d, 15.8, H-2', H-2"), 8.09, 8.06 (each 1H, d, 15.8, H-3', H-3"), 7.31, 7.31 (each 1H, dd, 8.0, 1.5, H-5', H-5"), 7.18, 7.18 (each 1H, d, 8.0, H-6', H-6"), 7.80, 7.56 (each 1H, brs, H- 9', H-9"). 13 CNMR (100.62Hz, pyridine-d 5 , ppm): 104.82 (C-1), 38.24 (C-2), 67.49 (C-3), 67.40 (C-4) , 78.01 (C-5), 80.45 (C-6), 64.18 (C-9), 170.97 (C-10), 167.95, 167.77 (C-1', C-1"), 115.97, 115.23 (C- 2', C-2"), 146.25, 146.21 (C-3', C-3"), 127.51, 127.28 (C-4', C-4"), 122.57, 122.31 (C-5', C- 5"), 116.84, 116.79 (C-6', C-6"), 150.37, 150.186 (C-7', C-7"), 147.62, 147.59 (C-8', C-8"), 116.13 , 115.89 (C-9', C-9").
该化合物具有独特结构骨架，虽然都具有两个咖啡酰基，但不同于结构已知的咖啡酰基奎宁酸，是结构新奇的化合物。The compound has a unique structural skeleton, and although it has two caffeoyl groups, it is different from the known structure of caffeoylquinic acid, and is a compound with a novel structure.
本发明公开飞蓬酯乙的制备方法，取灯盏细辛(Erigeron brevicapus)的全草或地上部分，粉碎，用0-95％乙醇水溶液或丙酮水溶液提取三次，合并三次提取液，减压浓缩。浓缩液上大孔树脂层析，先用水洗脱，再用40％，收集40％乙醇洗脱液后减压浓缩，此部分用Sephdex HL-20反复纯化便飞蓬酯乙(Erigeroster B)。The invention discloses a preparation method of Erigeron brevicapus. The whole herb or aerial part of Erigeron brevicapus is taken, crushed, extracted three times with 0-95% ethanol aqueous solution or acetone aqueous solution, combined three extracts, and concentrated under reduced pressure. The concentrated solution was subjected to macroporous resin chromatography, firstly eluted with water, then with 40% ethanol, and then concentrated under reduced pressure after collecting the 40% ethanol eluate. This part was repeatedly purified with Sephdex HL-20 to obtain Erigeroster B (Erigeroster B).
本发明公开飞蓬酯乙的药理活性研究结果，通过药理实验表明，飞蓬酯乙对体外肝组织匀浆脂质过氧化生成有明显的抑制作用，表明它们具有抗氧The present invention discloses the research results of the pharmacological activity of fennelyl ester B. Pharmacological experiments show that pheasantil B has obvious inhibitory effect on the formation of lipid peroxidation in liver tissue homogenate in vitro, indicating that they have anti-oxidative properties.
化活性。对ADP诱导大鼠的血小板聚集具有一定的抑制作用。对苯肾上腺素诱导兔主动脉收缩具有舒张作用，表明它们具有扩张血管作用。chemical activity. It has a certain inhibitory effect on ADP-induced platelet aggregation in rats. They have a relaxing effect on phenylephrine-induced contraction of rabbit aorta, indicating that they have a vasodilator effect.
表1.飞蓬酯乙对大鼠肝匀浆MDA含量的影响(i/n vitro)Table 1. Effects of Fiproxylate B on rat liver homogenate MDA content (i/n in vitro)
药品 剂量 N MDA含量(nmol/g组 抑制Drug Dose N N MDA Content (nmol/g group Inhibition
织湿重) 率(％)Wet Wet Weight) Rate (%)
空白对 32 81±21 -
照 According to
F(飞蓬酯 10 12 67±10* 18F (flying ester 10 12 67±10* 18
乙) μg/mlB) μg/ml
30 10 64±11* 2230 10 64±11* 22
μg/mlμg/ml
100 10 52±6** 36
μg/ml*P＜0.05，**P＜0.01vs空白对照组。 μg/ml*P<0.05, **P<0.01 vs blank control group.
表2.飞蓬酯乙对ADP诱导大鼠血小板聚集的作用Table 2. The effect of feponate B on platelet aggregation induced by ADP in rats
药品 剂量 n 最大聚 最大聚 平均聚集 平均聚集Drug Dose n n Maximum Aggregation Maximum Aggregation Average Aggregation Average Aggregation
(μg/ml) 集率 集抑制 率(％) 抑制率(μg/ml) Set Rate Set Inhibition Rate (%) Inhibition Rate
(％) 率(％) (％) (%) Rate(%) (%)
溶剂对照 7 79±80 0 71±9Solvent Control 7 79±80 0 71±9
250 6 75±7 5 54±18* 24飞蓬酯乙
750 7 71±9 10 48±25* 32P＜0.05，**P＜0.01vs溶剂对照组。
表3.飞蓬酯乙对苯肾上腺素诱导兔主动脉收缩的影响药品 浓度 样 苯肾上腺素诱发血管张 舒张Table 3. Effects of Feponate B on Phenylephrine-Induced Rabbit Aortic Contraction Drugs Concentration Sample Phenylephrine-Induced Vasodilation
μg/ 本 力(g) 百分μg/ Book Force (g) Percentage
ml 数 给药前对照 给药后 率溶剂对照 1 4.7±0.78 4.3±0.6 8％
5F(飞蓬酯乙) 100 9 4.4±0.6 3.± 23％
0.6****P＜0.01vs给药前对照 0.6****P<0.01vs the control before administration
鉴于飞蓬酯乙具有以上药理活性，因此预想飞蓬酯乙可用与治疗心脑血管疾病。In view of the above-mentioned pharmacological activities of phenanthridine, it is expected that phenanthridine can be used in the treatment of cardiovascular and cerebrovascular diseases.
本发明涉及的化合物可单独或与其它药用许可的的辅料按现有技术制成片剂、胶囊、滴丸、颗粒剂等口服剂型。将飞蓬酯乙单独或与其它药用许可的辅料配合后按现有方法制成注射液或冻干剂。The compounds involved in the present invention can be made into oral dosage forms such as tablets, capsules, dropping pills, granules, etc. alone or with other pharmaceutically acceptable auxiliary materials according to the prior art. After Fipronate B is prepared alone or in combination with other pharmaceutically approved auxiliary materials, it is prepared into injection or freeze-dried preparation according to the existing method.
化合物飞蓬酯(Erigeroster B)的口服剂型制备方法是将提取物单独或与其它药用许可的辅料配合后按现有方法制成片剂、胶囊等剂型。The preparation method of the oral dosage form of the compound Erigeroster B is to prepare the dosage forms such as tablets and capsules according to the existing method after the extract is combined alone or with other pharmaceutically approved adjuvants.
化合物飞蓬酯(Erigeroster B)的注射剂的制备方法是将提取物单独或与其它药用许可的辅料配合后按现有方法制成注射液或冻干剂。The preparation method of the injection of the compound Erigeroster B is that the extract is made into an injection or a freeze-dried preparation according to the existing method after the extract is combined alone or with other pharmaceutically approved adjuvants.
附图说明：图1为本发明化合物飞蓬酯乙的结构图。BRIEF DESCRIPTION OF THE DRAWINGS: Fig. 1 is a structural diagram of the compound of the present invention, fenponate B.
为了更好地理解本发明，本发明结合实施例进一步说明本发明的实质性内容，但本发明的内容并不局限于此。In order to better understand the present invention, the present invention further illustrates the substantive content of the present invention in conjunction with the examples, but the content of the present invention is not limited thereto.
实施例1：飞蓬酯乙的提取制备工艺Embodiment 1: the extraction and preparation technology of phyllonidyl ester B
取灯盏细辛(Erigeron brevicapus)的全草或地上部分50kg，粉碎，用70％Take 50kg of whole herb or aerial parts of Erigeron brevicapus, crush them, and use 70%
丙酮水溶液提取三次，合并三次提取液，减压浓缩。浓缩液上大孔树脂层析，先用水洗脱，再用40％，收集40％乙醇洗脱液后减压浓缩得提取物800g，此部分用Sephdex HL-20反复纯化便飞蓬酯乙(Erigeroster B)150g。The acetone aqueous solution was extracted three times, and the three extracts were combined and concentrated under reduced pressure. Macroporous resin chromatography on the concentrated solution, first eluting with water, then using 40%, collecting the 40% ethanol eluate and concentrating under reduced pressure to obtain 800g of the extract, which was repeatedly purified with Sephdex HL-20 to obtain Erigeroster B (Erigeroster B) 150g.
实施例2、飞蓬酯乙的片剂的制备工艺The preparation technology of the tablet of embodiment 2, fenponate B
片剂处方飞蓬酯乙 10g淀粉 50g10％淀粉浆 10g硬脂酸镁 2gPreasure of Pantodermid Puffer Puffer 10g of Starch 50g10 % Starch Pluffy 10g of Magnesium Magnesium 2g
将飞蓬酯乙与淀粉混合均匀后，加如10％的淀粉浆制成软材，过14目筛制粒，在70-80℃温度下干燥，过12目筛整粒，加硬脂酸镁混合后，压制成1000片，即得。每片含有效提取物10mg。After mixing Fipeng ester B and starch evenly, add 10% starch slurry to make soft material, pass through a 14-mesh sieve to granulate, dry at 70-80°C, pass through a 12-mesh sieve for granulation, and add magnesium stearate After mixing, it is pressed into 1000 pieces, that is to say. Each tablet contains 10mg of effective extract.
实施例3、飞蓬酯乙的胶囊剂制备工艺The capsule preparation technology of embodiment 3, fenponate second
胶囊剂处方飞蓬酯乙 10g淀粉 50g硬脂酸镁 2g ,
加处方量飞蓬酯乙，加80℃干燥的淀粉和硬脂酸镁混合均匀后，分装成1000粒胶囊，每粒胶囊含有提取物10mg。Add the prescription amount of Fipronate B, add starch and magnesium stearate dried at 80°C, mix evenly, and pack into 1000 capsules, each capsule contains 10mg of extract.
实施例4.飞蓬酯乙的注射剂制备Embodiment 4. The preparation of the injection of fenponate B
注射剂处方飞蓬酯 10g氯化钠 85g亚硫酸钠 2g
10g飞蓬酯乙溶解在5000ml冷的注射用蒸馏水中，85g氯化钠、2g亚硫酸钠混合后溶解在1000ml热的注射用蒸馏水中。将两种溶液混合，加水至10000ml，调节pH值在5.0-7.0滤棒过滤，膜过滤，澄明度检查合格后加氮气封瓶，在115℃，10atm压力下灭菌25分钟。Dissolve 10g of Fipronate B in 5000ml of cold distilled water for injection, mix 85g of sodium chloride and 2g of sodium sulfite and dissolve in 1000ml of hot distilled water for injection. Mix the two solutions, add water to 10000ml, adjust the pH value at 5.0-7.0, filter with a filter stick, filter with a membrane, seal the bottle with nitrogen after the clarity check is passed, and sterilize at 115°C and 10atm pressure for 25 minutes.
实施例5.飞蓬酯乙的注射用冻干剂制备Embodiment 5. The preparation of the lyophilized agent for injection of Filponate B
片剂处方飞蓬酯乙 10g碳酸氢钠 2g甘露醇 252g注射用水 加至2000mlPrescription Pantoderite ethyl 10g of sodium bicarbonate 2g of glycol 252g of injection water for 2000ml
按处方取辅料碳酸氢钠、氯化钠、甘露醇，加注射用水1600毫升溶解，加活性炭3.2g，吸附30分钟除热原，过滤除去活性碳，在滤液中加入飞蓬酯乙，超声处理使溶解，用1N盐酸调节pH为5.0～7.0，微孔滤膜滤过，加注射用水至2000ml，分装为1000支，冷冻干燥，上塞，轧盖，即得。Take auxiliary materials sodium bicarbonate, sodium chloride, and mannitol according to the prescription, add 1600 ml of water for injection to dissolve, add 3.2 g of activated carbon, absorb for 30 minutes to remove the pyrogen, filter to remove the activated carbon, add phylloxate B to the filtrate, and use ultrasonic treatment to make Dissolve, adjust the pH to 5.0-7.0 with 1N hydrochloric acid, filter through a microporous membrane, add water for injection to 2000ml, subpackage into 1000 tubes, freeze-dry, plug and cap, to obtain.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101974012A (en) * | 2010-10-26 | 2011-02-16 | 云南生物谷灯盏花药业有限公司 | Novel compound ethyl brevicate with pharmaceutical activity |
| CN101974010A (en) * | 2010-10-26 | 2011-02-16 | 云南生物谷灯盏花药业有限公司 | New compound erigeron breviscapus acid with officinal activity |
| CN101974011A (en) * | 2010-10-26 | 2011-02-16 | 云南生物谷灯盏花药业有限公司 | New compound methyl brevicate with medical activity |
| CN102079763A (en) * | 2009-11-30 | 2011-06-01 | 天津中医药大学 | Dioxabicyclo-octane compound, preparation method and application thereof |
| CN102351874A (en) * | 2011-08-24 | 2012-02-15 | 云南生物谷灯盏花药业有限公司 | New erigeroster compound with medicinal activity |
| CN101632724B (en) * | 2008-07-25 | 2012-03-28 | 贵州益佰制药股份有限公司 | Application of polygonum orientale and erigeron breviscapus composition in preparing medicaments for treating cerebrovascular disease and correlative diseases |
| CN102766179A (en) * | 2012-05-18 | 2012-11-07 | 云南施普瑞生物工程有限公司 | Extraction separation method of Erigeron Breviscapus related substance |
| CN105560227A (en) * | 2015-12-30 | 2016-05-11 | 神威药业集团有限公司 | Neuroprotection use and medicine of Dandengtongnao active component Erigoster B |
| CN118206596A (en) * | 2024-02-04 | 2024-06-18 | 中国科学院昆明植物研究所 | Rather than being used as medicine for treating ischemic cerebral apoplexy, erigeron acid and its extraction process and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101632724B (en) * | 2008-07-25 | 2012-03-28 | 贵州益佰制药股份有限公司 | Application of polygonum orientale and erigeron breviscapus composition in preparing medicaments for treating cerebrovascular disease and correlative diseases |
| CN102079763A (en) * | 2009-11-30 | 2011-06-01 | 天津中医药大学 | Dioxabicyclo-octane compound, preparation method and application thereof |
| CN101974012A (en) * | 2010-10-26 | 2011-02-16 | 云南生物谷灯盏花药业有限公司 | Novel compound ethyl brevicate with pharmaceutical activity |
| CN101974010A (en) * | 2010-10-26 | 2011-02-16 | 云南生物谷灯盏花药业有限公司 | New compound erigeron breviscapus acid with officinal activity |
| CN101974011A (en) * | 2010-10-26 | 2011-02-16 | 云南生物谷灯盏花药业有限公司 | New compound methyl brevicate with medical activity |
| CN102351874A (en) * | 2011-08-24 | 2012-02-15 | 云南生物谷灯盏花药业有限公司 | New erigeroster compound with medicinal activity |
| CN102351874B (en) * | 2011-08-24 | 2013-09-11 | 云南生物谷药业股份有限公司 | New erigeroster compound with medicinal activity |
| CN102766179A (en) * | 2012-05-18 | 2012-11-07 | 云南施普瑞生物工程有限公司 | Extraction separation method of Erigeron Breviscapus related substance |
| CN105560227A (en) * | 2015-12-30 | 2016-05-11 | 神威药业集团有限公司 | Neuroprotection use and medicine of Dandengtongnao active component Erigoster B |
| CN118206596A (en) * | 2024-02-04 | 2024-06-18 | 中国科学院昆明植物研究所 | Rather than being used as medicine for treating ischemic cerebral apoplexy, erigeron acid and its extraction process and application |
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