CN101278970A - 东紫苏类黄酮的制备方法及应用 - Google Patents
东紫苏类黄酮的制备方法及应用 Download PDFInfo
- Publication number
- CN101278970A CN101278970A CNA2008100584337A CN200810058433A CN101278970A CN 101278970 A CN101278970 A CN 101278970A CN A2008100584337 A CNA2008100584337 A CN A2008100584337A CN 200810058433 A CN200810058433 A CN 200810058433A CN 101278970 A CN101278970 A CN 101278970A
- Authority
- CN
- China
- Prior art keywords
- flavonoid
- ethyl acetate
- preparation
- elsholtzia
- total phenols
- 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.)
- Granted
Links
- 229930003935 flavonoid Natural products 0.000 title claims abstract description 29
- 150000002215 flavonoids Chemical class 0.000 title claims abstract description 29
- 235000017173 flavonoids Nutrition 0.000 title claims abstract description 29
- 241000119909 Elsholtzia bodinieri Species 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000243 solution Substances 0.000 claims abstract description 18
- 210000004369 blood Anatomy 0.000 claims abstract description 15
- 239000008280 blood Substances 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000002989 phenols Chemical class 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 11
- 238000010992 reflux Methods 0.000 claims abstract description 9
- 208000005189 Embolism Diseases 0.000 claims abstract description 7
- 208000001435 Thromboembolism Diseases 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims abstract description 7
- 238000002425 crystallisation Methods 0.000 claims abstract description 6
- 230000008025 crystallization Effects 0.000 claims abstract description 6
- 239000000463 material Substances 0.000 claims abstract description 5
- 239000002775 capsule Substances 0.000 claims abstract description 4
- 239000008187 granular material Substances 0.000 claims abstract description 4
- 238000002347 injection Methods 0.000 claims abstract description 3
- 239000007924 injection Substances 0.000 claims abstract description 3
- 229940098465 tincture Drugs 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 11
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 10
- 239000012141 concentrate Substances 0.000 claims description 6
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- -1 tincture Substances 0.000 claims description 2
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 208000019553 vascular disease Diseases 0.000 claims 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 12
- 239000000284 extract Substances 0.000 abstract description 7
- 208000026106 cerebrovascular disease Diseases 0.000 abstract description 5
- 235000012000 cholesterol Nutrition 0.000 abstract description 4
- 239000000725 suspension Substances 0.000 abstract 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract 1
- 239000000654 additive Substances 0.000 abstract 1
- 230000000996 additive effect Effects 0.000 abstract 1
- 230000037396 body weight Effects 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 14
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 10
- 208000032843 Hemorrhage Diseases 0.000 description 9
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000000740 bleeding effect Effects 0.000 description 7
- 210000002381 plasma Anatomy 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- 208000024172 Cardiovascular disease Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 230000001939 inductive effect Effects 0.000 description 6
- 206010053567 Coagulopathies Diseases 0.000 description 5
- 108010023302 HDL Cholesterol Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 230000035602 clotting Effects 0.000 description 5
- 239000003651 drinking water Substances 0.000 description 5
- 235000020188 drinking water Nutrition 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 230000029058 respiratory gaseous exchange Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 241000581650 Ivesia Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- 241000131458 Elsholtzia Species 0.000 description 2
- 241001122767 Theaceae Species 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 201000005577 familial hyperlipidemia Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229960004555 rutoside Drugs 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- LDTDRTSKWGQBAA-IPOZFMEPSA-N 2-(3,4-dihydroxyphenyl)-5-hydroxy-7-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-4-one Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C=C3C(C(C=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 LDTDRTSKWGQBAA-IPOZFMEPSA-N 0.000 description 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- IVCZEZUJCMWBBR-UHFFFAOYSA-N 7-O-beta-D-glucopyranosyl-7,3',4'-trihydroxyflavone Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C=C(C=3C=C(O)C(O)=CC=3)OC2=C1 IVCZEZUJCMWBBR-UHFFFAOYSA-N 0.000 description 1
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- RAFHNDRXYHOLSH-UHFFFAOYSA-N Eriodictyol-7-beta-D-glucopyranosid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C(C(=O)CC(O2)C=3C=C(O)C(O)=CC=3)C2=C1 RAFHNDRXYHOLSH-UHFFFAOYSA-N 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000207923 Lamiaceae Species 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 241001529246 Platymiscium Species 0.000 description 1
- KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282894 Sus scrofa domesticus Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000003035 anti-peroxidant effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- RAFHNDRXYHOLSH-SFTVRKLSSA-N eriodictyol 7-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C(C(=O)C[C@H](O2)C=3C=C(O)C(O)=CC=3)C2=C1 RAFHNDRXYHOLSH-SFTVRKLSSA-N 0.000 description 1
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 235000015092 herbal tea Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 235000008777 kaempferol Nutrition 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- NBSPOAXOBIRHSH-UHFFFAOYSA-N luteolin 7-O-beta-D-glucopyranoside Natural products OCC1CC(Oc2cc(O)c3C(=O)C=C(Oc3c2)c4ccc(O)c(O)c4)C(O)C(O)C1O NBSPOAXOBIRHSH-UHFFFAOYSA-N 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 238000004382 potting Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960002662 propylthiouracil Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000021595 spermatogenesis Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 239000008802 xuezhikang Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明是一种东紫苏类黄酮的制备方法及应用。制备方法是:取东紫苏,净制,粉碎,用含水醇提取1~3次,物料比为1∶5~1∶25;提取液合并,过滤,浓缩成1.05~1.20·50℃浸膏;取该浸膏加入3~10倍量水,搅拌混悬,用碱调pH=9~10,过滤,用乙酸乙酯萃取3次,所得水层溶液再用酸调pH=1~3,乙酸乙酯萃取3次,浓缩乙酸乙酯溶液,得总酚成分;总酚成分用乙醇回流溶解,趁热过滤,放置结晶,得类黄酮。加入药物制剂允许加入的助剂,制成包括口服液、酊剂、片剂、胶囊、颗粒剂及注射剂在内的药品,用于防治心脑血管性疾病,血脂及胆固醇过高、血栓栓塞等疾病。
Description
技术领域
本发明涉及药品技术领域,具体地说是以东紫苏为原料制备类黄酮的方法及其在心脑血管疾病方面的应用。
背景技术
唇形科香薷属(Elsholtzia)植物在我国约30种,其中云南就有20多种,资源十分丰富,多数品种均可入药,为传统常用中药。东紫苏为香薷属植物Elsholtzia bodinieriVan’t.的全草,又名凉茶、山茶、香茶、宝珠茶,味甘苦微幸,性平,能“发散解表,理气和胃,治外感风寒,消化不良”,滇南各地少数民族作为日常茶饮广泛应用。
发明内容
本发明的目的在于提供一种能保留其活性物质的东紫苏类黄酮的制备方法,以及其在治疗心脑血管疾病药物中的应用。
东紫苏中含圣草素7-O-β-D-葡萄吡喃糖苷,木犀草素7-O-β-D-葡萄吡喃糖苷,山奈酚3-O-芦丁糖苷,芦丁等类黄酮及2,6-二甲基-8-羟基-2,6-辛二烯酸-8-O-β-D-葡萄吡喃糖苷多种活性成分,是强烈的抗脂质过氧化剂和高血脂、高胆固醇平衡剂,能有效增强血管通透性和调节血液流变学指标,是天然的心脑血管疾病防治药物。针对本品现有应用状态,把东紫苏深加工,提取浓缩、精制其心脑血管疾病的有效成分——类黄酮,应用于食品、保健品及药品,具有巨大的商业经济前景。
本发明的目的通过以下技术方案予以实现:
东紫苏类黄酮制备方法,包括以下步骤:
(1)取东紫苏净制、粉碎,用含水乙醇提取1~3次,物料比为1∶5~1∶25;
(2)提取液合并,过滤,浓缩成1.05~1.20(50℃)浸膏;
(3)取该浸膏加入3~5倍量水,搅拌混悬,用碱调pH=9~10,过滤,用乙酸乙酯萃取3次,所得水层溶液再用酸调pH=1~3,乙酸乙酯萃取3次,浓缩乙酸乙酯溶液,得总酚成分。
(4)总酚成分用乙醇回流溶解,趁热过滤,放置结晶,得类黄酮。
取类黄酮,加入相关辅料,制成药品,包括口服液、酊剂、片剂、胶囊、冲剂(颗粒剂)及注射剂等。
本发明中的东紫苏类黄酮及其制剂可用于心脑血管疾病防治。
东紫苏类黄酮功能活性试验如下:
1、试验材料
1.1、供试样品
SC-1(东紫苏类黄酮)为淡黄色粉剂,样品水溶性差,体外试验用DMSO助溶,口服样品用0.5%羧甲基纤维素助悬,饮用水稀释至一定容积,小鼠按0.2ml/10g体重ig,大鼠按1ml/100g体重ig。
1.2、其他药品试剂
血脂康胶囊由北京北大维信生物科技有限公司生产,批号20050626阿司匹林由山东新华制药公司提供,二磷酸腺苷(adenosine diphosphate,ADP)、血小板活化因子(plateletactivating facter,PAF)及花生四烯酸(arachidonic acid,AA)系sigma公司产品,血清总胆固醇(TC)、甘油三酯(TG)及高密度脂量白一胆固醇(HDL-C)测定试剂盒购自北京中生北控生物科技股份有限公司。灯盏花素片为云南植物药业有限公司产品,批号20040402。
1.3、主要仪器设备
LBY-NJ2型血液凝聚仪由北京普制生精密仪器研究中心生产,日本岛津公司生产CL-770型临床分光光度仪,北京赛科希德SA-6000型锥板粘度计等。
1.4、实验动物
SD大鼠、ICR小鼠为SPF级,家兔为普通级,实验动物生产许可证号:SCXK(滇)2005-0008,由昆明医学院实验动物中心提供。
2、方法与结果
2.1、统计学方法
实验结果用X±S表示,组间差异用t检验,P<0.05表示组间差异有显著性。
2.2、对血小板聚集功能的影响
2.2.1、富血小板血浆(platelet-rich plasma,PRP)和贫血小板血浆(platelet-poorplasma,PPP)的制备。
自清醒家兔颈动脉取血收集于塑料离心管中,用3.8%枸橼酸钠抗凝(血与抗凝剂体积之比为9∶1),1000rpm离心10min得PRP,吸出PRP后剩余血液再以3000rpm离心10min得PPP,PPP用于调零或调整PRP中血小板的数目,试验中血小板数控制在5×1011/L
2.2.2、血小板聚集性测定
按Born’s比浊法测定样品不同浓度对ADP,PAF和AA诱导的血小板聚集的影响,即将样品与PRP共同温育10min,再加入不同诱导剂(终浓度分别为ADP3μmol/L,PAF7.2nmol/L,AA0.35mmol/L),测定5min内血小板最大聚集率(%)。结果见表1。
表1 SC-1体外对ADP、PAF或AA诱导血小板聚集功能的影响
结果表明,SC-1有显著抑制ADP诱导的血小板聚集作用,该作用呈一定的浓度相关性;对PAF、AA诱导的血小板聚集,只在较高浓度有抑制作用(80mg/L)。
2.2.3对小鼠断头后张口喘气时间的影响
选用ICR小鼠50只,雌雄各半,体重18~22g,按体重随机分为5组,即空白对照组,阳性对照组(灯盏花素片100mg、kg-1、d-1)及SC-1低、中、高剂量组和WF-1低、中、高剂量组(分别按50、100、200mg、kg-1、d-1给药),样品用饮用水稀释至一定容积,按0.2ml/10g体重ig,每天一次,空白对照组ig等体积饮用水。连续给药(或水)6天。末次给药后1h进行断头张口喘息时间测定。
结果显示,除灯盏花素片组(100mg/kg)有显著延长小鼠断头后张口喘气时间外,其他各组喘气时间与空白对照组比均无显著差异(表2)。
表2 SC-1对小鼠断头张口喘气时间的影响
2.2.4对出血时间的影响
选用ICR小鼠50只,雌雄各半,体重18~22g,按体重随机分成5组,分组及给药量同前,阳性对照改用阿司匹林(30mg/kg),连续给药5天,末次给药后1h用断尾法进行出血时间测定,将小鼠尾尖8mm处剪断,从出血开始(滤纸上出现血迹)计时,每半分钟用滤纸吸去血滴一次,直到出血自然停止(滤纸上无血迹),所计时间即为出血时间。
结果显示,SC-1有一定延长出血时间倾向,但与空白对照组比无显著差异(P>0.05),见表3
表3 SC-1、WF-1对小鼠尾尖出血时间的影响
2.2.5 对凝血时间的影响—毛细玻璃管法
选用ICR小鼠50只,雌雄各半,体重20~24g,按体重随机分为5组,分组及给药量与观察对出血时间影响相同。按分组连续给药5天,末次给药后1h用毛细玻管法进行凝血时间测定。取内径1mm、长10cm毛细玻管自小鼠一侧眼球内眦插入球后静脉丛,深的4~5mm,至血液流入毛细玻管内开始计时,血液注满后将毛细玻管取出平放于桌上,每隔30秒折断二端毛细管约0.5cm,至血凝丝出现为止,所历时间即为凝血时间。
表4 SC-1对小鼠凝血时间的影响
结果表明,SC-1有延长小鼠凝血时间作用。
2.2.6 对ADP诱发小鼠肺微循环血栓形成的影响
ICR小鼠50只,雌雄各半,体重18~20g,按体重随机分为5组,分组及给药量同前,连续灌胃给药5天,末次给药后1h按文献方法于小鼠尾静脉iv 400mg/kg的ADP生理盐水溶液(0.1ml/10g体重),注毕,观察并记录15min内动物死亡数,计算死亡抑制率。
结果表明:100和200mg/kg体重SC-1有显著降低静脉注射ADP所导致的肺微血管栓塞动物死亡数,该作用呈剂量依赖趋势(表5)
表5 SC-1、WF-1对ADP致小鼠肺栓塞死亡的保护作用
与空白对照组比aP<0.01,bP<0.05
2.2.7对小鼠实验性高脂血症血脂水平的影响
雄性ICR小鼠50只,体重18~22g,按体重随机分为5组,全部动物饲以含高脂肪,高胆固醇饲料,自由进食,饮水不限。高脂饲料配方为(W∶W):胆固醇2%,蛋黄10%,猪油7%,丙基硫氧嘧啶0.1%,胆酸钠0.3%,基础饲料80.6%,在进食高脂饲料的同时,各给药组按分组灌胃给予不同剂量的药物,空白对照组给相同体积饮用水。5天后摘眼球取禁食12h空腹血,用酶法按试剂盒说明书操作程序,测血清总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白—胆固醇(HDL-C),结果见表6。
结果表明,SC-1灌胃给药有降低实验性高脂血症小鼠血清TC和TG作用,该作用呈剂量相关性,200mg/kg体重降低TC和TG作用十分显著,与模型组比P<0.01,随着TC下降,HDL-C也有一定降低,但HDL-C/TC比值略有升高,说明样品对脂蛋白分布无有害影响。
表6 SC-1对小鼠实验性高脂血症的影响
n=10 x±s aP<0.01与高脂对照组比较
2.2.8 对血浆粘度的影响
雄性SD大鼠40只,体重200~240g,按体重随机分为4组,分组及给药量同前,高脂饲料喂养,饲料配方不变,连续给药7天,禁食12h后由股动脉取血,1%肝素抗凝,分离血浆(3000rpm,10min),用北京赛科希德SA-6000型锥板粘度计进行血浆粘度测定。结果显示,SC-1无明显影响大鼠血浆粘度作用(表7)
表7 SC-1、WF-1对大鼠血浆粘度的影响
小结:初步实验结果显示,SC-1有较好的抑制ADP诱导的家兔血小板聚集作用,终浓度分别为20mg/L(SC-1)即可显著抑制ADP诱导的血小板聚集(P<0.01=,此外,SC-1在较高浓度(80mg/L)有抑制AA诱导的血小板聚集作用。体内灌胃给药,SC-1可显著延长小鼠的凝血时间,对出血时间无明显影响;SC-1 100-200mg/kg可明显降低ADP致小鼠肺微血管栓塞的死亡数;200mg/kg显著降低实验性高脂血症小鼠血清TC、TG水平,对大鼠血浆粘度无明显影响。以上结果提示,SC-1具有改变血液流变学,防治心脑血管疾病作用。
具体实施方式
下面结合实施例,对本发明作进一步的详细说明,但不是对本发明的限定。
实施例1:
取东紫苏10公斤,净制,粉碎,用75%含水乙醇100公斤回流提取3次,每次2小时,提取液合并,过滤,浓缩至密度1.10(50℃),得浸膏2.02公斤,加水6公斤,用NaOH液调pH=10,过滤,用乙酸乙酯萃取3次,所得水层溶液再用盐酸调pH=1~3,用乙酸乙酯萃取3次,浓缩该乙酸乙酯溶液,得总酚成分。总酚成分用乙醇回流溶解,趁热过滤,放置结晶,得类黄酮268g。
实施例2:
取东紫苏1公斤,净制,粉碎,用50%含水乙醇5公斤回流提取3次,每次2小时,提取液合并,过滤,浓缩至密度1.05(50℃),得浸膏0.17公斤,加水1公斤,用碱液调pH=9,过滤,用乙酸乙酯萃取3次,所得水层溶液再用盐酸调pH=2,用乙酸乙酯萃取3次,浓缩该乙酸乙酯溶液,得总酚成分。总酚成分用乙醇回流溶解,趁热过滤,放置结晶,得类黄酮18.8g。
实施例3:
取东紫苏5公斤,净制,粉碎,用30%含水乙醇125公斤回流提取3小时,提取液过滤,浓缩至密度1.20(50℃),得浸膏0.92公斤,加水8公斤,用碱液调pH=9,过滤,用乙酸乙酯萃取3次,所得水层溶液再用盐酸调pH=3用乙酸乙酯萃取3次,浓缩该乙酸乙酯溶液,得总酚成分。总酚成分用乙醇回流溶解,趁热过滤,放置结晶,得类黄酮112.4g。
应用实施例1:
取实施例1~3中的类黄酮制成制剂:
取类黄酮100g,加入蔗糖150g,制粒,填装成胶囊1000粒(每粒含类黄酮100mg);每日服用2~3次,每次1~3粒,用于防治心脑缺血、血脂及胆固醇过高、预防血栓栓塞等。
应用实施例2:
取类黄酮100g,加入水500ml,加入NaOH液不断搅拌,至完全溶解,再用盐酸调pH=7.5,加水至1000ml,混匀,过滤,罐封成口服液1000支(每支含类黄酮100mg);每日服用2~3次,每次1~3支,用于防治心脑缺血、血脂及胆固醇过高、预防血栓栓塞等。
Claims (3)
1、一种东紫苏类黄酮的制备方法,其特征在于按以下步骤进行:
(1)取东紫苏,净制,粉碎,用含水醇提取1~3次,物料比为1∶5~1∶25;
(2)提取液合并,过滤,浓缩成1.05~1.20·50℃浸膏;
(3)取该浸膏加入3~10倍量水,搅拌混悬,用碱调pH=9~10,过滤,用乙酸乙酯萃取3次,所得水层溶液再用酸调pH=1~3,乙酸乙酯萃取3次,浓缩乙酸乙酯溶液,得总酚成分;
(4)总酚成分用乙醇回流溶解,趁热过滤,放置结晶,得类黄酮。
2、权利要求1所述的东紫苏类黄酮的制备方法所得到的类黄酮的应用,其特征在于用于防治心脑血管性疾病,血脂及胆固醇过高、血栓栓塞。
3、根据权利要求2所述的东紫苏类黄酮的制备方法所得到的类黄酮的应用,其特征在于加入药物制剂允许加入的助剂,制成包括口服液、酊剂、片剂、胶囊、颗粒剂及注射剂在内的药品。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008100584337A CN101278970B (zh) | 2008-05-23 | 2008-05-23 | 东紫苏类黄酮的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008100584337A CN101278970B (zh) | 2008-05-23 | 2008-05-23 | 东紫苏类黄酮的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101278970A true CN101278970A (zh) | 2008-10-08 |
CN101278970B CN101278970B (zh) | 2011-12-07 |
Family
ID=40011757
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2008100584337A Expired - Fee Related CN101278970B (zh) | 2008-05-23 | 2008-05-23 | 东紫苏类黄酮的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101278970B (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104171211A (zh) * | 2014-09-11 | 2014-12-03 | 勐海茶业有限责任公司 | 一种凉茶及其制备方法 |
CN105147772A (zh) * | 2015-06-18 | 2015-12-16 | 齐珈娆 | 紫苏黄酮类化合物的提取及鉴定 |
CN105267299A (zh) * | 2015-09-22 | 2016-01-27 | 盐城工学院 | 紫苏中黄酮及其衍生物的提取方法 |
CN109105949A (zh) * | 2018-07-05 | 2019-01-01 | 湖北中烟工业有限责任公司 | 一种紫苏提取物的分段提取制备方法及其应用 |
-
2008
- 2008-05-23 CN CN2008100584337A patent/CN101278970B/zh not_active Expired - Fee Related
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104171211A (zh) * | 2014-09-11 | 2014-12-03 | 勐海茶业有限责任公司 | 一种凉茶及其制备方法 |
CN105147772A (zh) * | 2015-06-18 | 2015-12-16 | 齐珈娆 | 紫苏黄酮类化合物的提取及鉴定 |
CN105267299A (zh) * | 2015-09-22 | 2016-01-27 | 盐城工学院 | 紫苏中黄酮及其衍生物的提取方法 |
CN109105949A (zh) * | 2018-07-05 | 2019-01-01 | 湖北中烟工业有限责任公司 | 一种紫苏提取物的分段提取制备方法及其应用 |
Also Published As
Publication number | Publication date |
---|---|
CN101278970B (zh) | 2011-12-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104013668B (zh) | 甘草黄酮类提取物用于制备治疗溃疡性结肠炎药物中应用 | |
CN104435226B (zh) | 鸡矢藤提取物及其用途 | |
CN107648430A (zh) | 一种含延龄草甾体皂苷类有效成分胶囊制剂的制备方法及其在制备各类药物中的应用 | |
CN109453212A (zh) | 一种具有抗癌作用的毛诃子提取物及其有效部位制备方法 | |
CN104922176B (zh) | 一种野菊花提取物的应用 | |
CN101278970B (zh) | 东紫苏类黄酮的制备方法 | |
CN106798762A (zh) | 一种植物提取物及其制备方法和应用 | |
CN102552644A (zh) | 大蒜总多糖的抗癌用途、制备方法及组合物 | |
CN104435034B (zh) | 一种三七总皂苷及其制备方法 | |
CN103860638B (zh) | 苦豆子黄酮组合物的制备方法及医药新用途 | |
CN109045035A (zh) | 7-(2,2-二甲基-3-丁烯酰胺基)-八氢苯喹啉乙酸酯在制备治疗肝病药物的应用 | |
CN101849950A (zh) | 救必应酸在制备调血脂的药物中的应用 | |
CN102526170B (zh) | 抗结核杆菌的儿茶提取物组合物、其制备方法及含有它们的药物制剂和应用 | |
CN104147104B (zh) | 山豆根黄酮组合物在制备具有降低血糖同时防治高血脂症药物中的应用 | |
CN102365089A (zh) | 一种预防和治疗阿尔茨海默氏症的药物及其制备方法 | |
CN113730463A (zh) | 香连丸产物的新用途 | |
CN113730464A (zh) | 香连丸及其提取物、药物组合物与香连丸产物的新用途 | |
CN110511290A (zh) | 一种具有降高尿酸作用的红豆杉多糖的制备方法及其应用 | |
CN103977390B (zh) | 一种生姜洋葱药酒组合物的制备方法及其用途 | |
CN1985917B (zh) | 用于降血糖、降血脂、控制糖尿病并发症的组合物 | |
KR101534142B1 (ko) | 혼합 생약 추출물을 이용한 대사성질환 예방 및 치료용 조성물 | |
JPH0519554B2 (zh) | ||
CN106361811B (zh) | 一种通脉药物组合物及其制备方法 | |
CN108042661A (zh) | 富含二氢杨梅素的白茶提取物和制备医药健康产品的用途 | |
CN103110680A (zh) | 一种短葶飞蓬总酚酸的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C17 | Cessation of patent right | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20111207 Termination date: 20140523 |