CN108785370B - 一种用于治疗高血脂症及动脉粥样硬化的药物组合物 - Google Patents
一种用于治疗高血脂症及动脉粥样硬化的药物组合物 Download PDFInfo
- Publication number
- CN108785370B CN108785370B CN201710312895.6A CN201710312895A CN108785370B CN 108785370 B CN108785370 B CN 108785370B CN 201710312895 A CN201710312895 A CN 201710312895A CN 108785370 B CN108785370 B CN 108785370B
- Authority
- CN
- China
- Prior art keywords
- parts
- pharmaceutical composition
- polysaccharide
- preparation
- weight
- 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.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 77
- 201000001320 Atherosclerosis Diseases 0.000 title claims abstract description 47
- 208000031226 Hyperlipidaemia Diseases 0.000 title claims abstract description 31
- 150000004676 glycans Chemical class 0.000 claims abstract description 58
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 58
- 239000005017 polysaccharide Substances 0.000 claims abstract description 58
- ZQSIJRDFPHDXIC-UHFFFAOYSA-N Daidzein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 claims abstract description 57
- LXBIFEVIBLOUGU-JGWLITMVSA-N duvoglustat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-JGWLITMVSA-N 0.000 claims abstract description 34
- 241001061264 Astragalus Species 0.000 claims abstract description 29
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 claims abstract description 29
- 235000006533 astragalus Nutrition 0.000 claims abstract description 29
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 claims abstract description 29
- 210000004233 talus Anatomy 0.000 claims abstract description 29
- GMTUGPYJRUMVTC-UHFFFAOYSA-N Daidzin Natural products OC(COc1ccc2C(=O)C(=COc2c1)c3ccc(O)cc3)C(O)C(O)C(O)C=O GMTUGPYJRUMVTC-UHFFFAOYSA-N 0.000 claims abstract description 27
- KYQZWONCHDNPDP-UHFFFAOYSA-N Daidzoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-UHFFFAOYSA-N 0.000 claims abstract description 27
- KYQZWONCHDNPDP-QNDFHXLGSA-N daidzein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-QNDFHXLGSA-N 0.000 claims abstract description 27
- -1 calycosin glucoside Chemical class 0.000 claims abstract description 25
- 244000046146 Pueraria lobata Species 0.000 claims abstract description 21
- 235000010575 Pueraria lobata Nutrition 0.000 claims abstract description 21
- ZZAJQOPSWWVMBI-UHFFFAOYSA-N Calycosin Natural products C1=C(O)C(OC)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZZAJQOPSWWVMBI-UHFFFAOYSA-N 0.000 claims abstract description 20
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229930182478 glucoside Natural products 0.000 claims abstract description 20
- LXBIFEVIBLOUGU-UHFFFAOYSA-N Deoxymannojirimycin Natural products OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 claims abstract description 17
- QMNWISYXSJWHRY-BCBPIKMJSA-N astragaloside IV Natural products CC(C)(O)[C@@H]1CC[C@@](C)(O1)[C@H]2[C@@H](O)C[C@@]3(C)[C@@H]4C[C@H](O[C@@H]5O[C@H](CO)[C@H](O)[C@@H](O)[C@H]5O)[C@H]6C(C)(C)[C@H](CC[C@@]67C[C@@]47CC[C@]23C)O[C@@H]8OC[C@@H](O)[C@H](O)[C@H]8O QMNWISYXSJWHRY-BCBPIKMJSA-N 0.000 claims abstract description 17
- QMNWISYXSJWHRY-YLNUDOOFSA-N astragaloside IV Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)[C@H]4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C[C@H]3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-YLNUDOOFSA-N 0.000 claims abstract description 17
- PFKIBRPYVNVMRU-UHFFFAOYSA-N cyclosieversioside F Natural products CC(C)(O)C1COC(C)(C1)C2C(O)CC3(C)C4CC(OC5OC(CO)C(O)C(O)C5O)C6C(C)(C)C(CCC67CC47CCC23C)OC8OCC(O)C(O)C8O PFKIBRPYVNVMRU-UHFFFAOYSA-N 0.000 claims abstract description 17
- YXOLAZRVSSWPPT-UHFFFAOYSA-N Morin Chemical compound OC1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 YXOLAZRVSSWPPT-UHFFFAOYSA-N 0.000 claims abstract description 14
- 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 claims abstract description 14
- 235000007708 morin Nutrition 0.000 claims abstract description 14
- 235000008708 Morus alba Nutrition 0.000 claims abstract description 13
- 240000000249 Morus alba Species 0.000 claims abstract description 13
- 239000003937 drug carrier Substances 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims description 77
- 239000004480 active ingredient Substances 0.000 claims description 28
- 239000000463 material Substances 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 20
- 238000002156 mixing Methods 0.000 claims description 17
- 241000219780 Pueraria Species 0.000 claims description 8
- 229940107666 astragalus root Drugs 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 claims description 5
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims 1
- 229930182490 saponin Natural products 0.000 claims 1
- 150000007949 saponins Chemical class 0.000 claims 1
- HKQYGTCOTHHOMP-UHFFFAOYSA-N formononetin Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC=C2C1=O HKQYGTCOTHHOMP-UHFFFAOYSA-N 0.000 abstract description 30
- RODXRVNMMDRFIK-UHFFFAOYSA-N scopoletin Chemical compound C1=CC(=O)OC2=C1C=C(OC)C(O)=C2 RODXRVNMMDRFIK-UHFFFAOYSA-N 0.000 abstract description 25
- 230000000694 effects Effects 0.000 abstract description 20
- HPSWAEGGWLOOKT-VUNDNAJOSA-N cis-Mulberroside A Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C=C1O)=CC=C1\C=C\C1=CC(O)=CC(O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 HPSWAEGGWLOOKT-VUNDNAJOSA-N 0.000 abstract description 16
- HPSWAEGGWLOOKT-UHFFFAOYSA-N cis-mulberroside A Natural products OC1C(O)C(O)C(CO)OC1OC(C=C1O)=CC=C1C=CC1=CC(O)=CC(OC2C(C(O)C(O)C(CO)O2)O)=C1 HPSWAEGGWLOOKT-UHFFFAOYSA-N 0.000 abstract description 16
- LVBLYMQWWGLBRE-UHFFFAOYSA-N Astragaloside-II Chemical compound CC(=O)OC1C(C(COC1OC2CCC34CC35CCC6(C(C(CC6(C5CC(C4C2)OC7C(C(C(C(O7)CO)O)O)O)C)O)C8(CCC(O8)C(C)(C)O)C)C)O)O LVBLYMQWWGLBRE-UHFFFAOYSA-N 0.000 abstract description 15
- JLKGXASMCRAVAK-UHFFFAOYSA-N Astragaloside-II Natural products CC(=O)OC1C(O)C(O)COC1OC2CCC34CC35CCC6(C)C(C)(CCC6(O)C7(C)CCC(O7)C(C)(C)O)C5CC(OC8OC(CO)C(O)C(O)C8O)C4C2(C)C JLKGXASMCRAVAK-UHFFFAOYSA-N 0.000 abstract description 15
- DJHCVWLJAINILQ-UHFFFAOYSA-N Cyclosieversioside D Natural products CC(=O)OC1C(O)C(O)COC1OC2CCC34CC35CCC6(C)C(C(O)CC6(C)C5CC(OC7OC(CO)C(O)C(O)C7O)C4C2(C)C)C8(C)CC(CO8)C(C)(C)O DJHCVWLJAINILQ-UHFFFAOYSA-N 0.000 abstract description 15
- 235000007240 daidzein Nutrition 0.000 abstract description 15
- RIKPNWPEMPODJD-UHFFFAOYSA-N formononetin Natural products C1=CC(OC)=CC=C1C1=COC2=CC=CC=C2C1=O RIKPNWPEMPODJD-UHFFFAOYSA-N 0.000 abstract description 15
- XETHJOZXBVWLLM-HUKCQOFTSA-N (5ar,10as)-2-[(1s,5s,6r)-6-(2,4-dihydroxybenzoyl)-5-(2,4-dihydroxyphenyl)-3-methylcyclohex-2-en-1-yl]-1,3,8,10a-tetrahydroxy-5a-(3-methylbut-2-enyl)-[1]benzofuro[3,2-b]chromen-11-one Chemical compound O=C([C@@H]1[C@H](CC(C)=C[C@@H]1C1=C(O)C=C2O[C@]3([C@](C(=O)C2=C1O)(O)OC=1C3=CC=C(O)C=1)CC=C(C)C)C=1C(=CC(O)=CC=1)O)C1=CC=C(O)C=C1O XETHJOZXBVWLLM-HUKCQOFTSA-N 0.000 abstract description 14
- XEHFSYYAGCUKEN-UHFFFAOYSA-N Dihydroscopoletin Natural products C1CC(=O)OC2=C1C=C(OC)C(O)=C2 XEHFSYYAGCUKEN-UHFFFAOYSA-N 0.000 abstract description 14
- ZCOLJUOHXJRHDI-FZHKGVQDSA-N Genistein 7-O-glucoside Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)c1cc(O)c2C(=O)C(c3ccc(O)cc3)=COc2c1 ZCOLJUOHXJRHDI-FZHKGVQDSA-N 0.000 abstract description 14
- CJPNHKPXZYYCME-UHFFFAOYSA-N Genistin Natural products OCC1OC(Oc2ccc(O)c3OC(=CC(=O)c23)c4ccc(O)cc4)C(O)C(O)C1O CJPNHKPXZYYCME-UHFFFAOYSA-N 0.000 abstract description 14
- YCUNGEJJOMKCGZ-UHFFFAOYSA-N Pallidiflorin Natural products C1=CC(OC)=CC=C1C1=COC2=CC=CC(O)=C2C1=O YCUNGEJJOMKCGZ-UHFFFAOYSA-N 0.000 abstract description 14
- SUOXGDJCEWTZIZ-UHFFFAOYSA-N Sanggenon C Natural products OC1=C2C(=O)C3(CC=C(C)C)OC4=CC(O)=CC=C4C3(O)OC2=CC(O)=C1C1C=C(C)CC(C=2C(=CC(O)=CC=2)O)C1C(=O)C1=CC=C(O)C=C1O SUOXGDJCEWTZIZ-UHFFFAOYSA-N 0.000 abstract description 14
- NUKIHHJPIBKEPM-UHFFFAOYSA-N Sanggenon D Natural products CC(=CCC12Oc3cc(O)ccc3C1(O)Oc4cc(O)c(C5C=C(C)CC(C5C(=O)c6cc(O)cc(O)c6)c7ccc(O)cc7O)c(O)c4C2=O)C NUKIHHJPIBKEPM-UHFFFAOYSA-N 0.000 abstract description 14
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 abstract description 14
- FWYIBGHGBOVPNL-UHFFFAOYSA-N scopoletin Natural products COC=1C=C2C=CC(OC2=C(C1)O)=O FWYIBGHGBOVPNL-UHFFFAOYSA-N 0.000 abstract description 14
- 210000000709 aorta Anatomy 0.000 abstract description 9
- 230000001105 regulatory effect Effects 0.000 abstract description 5
- 238000011830 transgenic mouse model Methods 0.000 abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 100
- 239000000243 solution Substances 0.000 description 36
- 239000000284 extract Substances 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 14
- 239000002994 raw material Substances 0.000 description 12
- 238000010992 reflux Methods 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 238000005227 gel permeation chromatography Methods 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 239000008280 blood Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000011347 resin Substances 0.000 description 9
- 229920005989 resin Polymers 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 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 description 8
- 238000011068 loading method Methods 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 108010023302 HDL Cholesterol Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 6
- 230000007812 deficiency Effects 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 206010012735 Diarrhoea Diseases 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 108010028554 LDL Cholesterol Proteins 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000001603 reducing effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 2
- 108010000912 Egg Proteins Proteins 0.000 description 2
- 239000009636 Huang Qi Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 206010003549 asthenia Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000000779 depleting effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 235000013345 egg yolk Nutrition 0.000 description 2
- 210000002969 egg yolk Anatomy 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000035922 thirst Effects 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- HDHRTQZSBFUBMJ-UHFFFAOYSA-N Artonin E Natural products O1C2=C3C=CC(C)(C)OC3=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC(O)=C(O)C=C1O HDHRTQZSBFUBMJ-UHFFFAOYSA-N 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 229940123239 Cholesterol synthesis inhibitor Drugs 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000036119 Frailty Diseases 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000219925 Oenothera Species 0.000 description 1
- 235000004496 Oenothera biennis Nutrition 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 206010030302 Oliguria Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 206010038084 Rectocele Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000033809 Suppuration Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000031971 Yin Deficiency Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 208000019902 chronic diarrheal disease Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- XFFOMNJIDRDDLQ-UHFFFAOYSA-N morusin Chemical compound O1C2=C3C=CC(C)(C)OC3=CC(O)=C2C(=O)C(CC=C(C)C)=C1C1=CC=C(O)C=C1O XFFOMNJIDRDDLQ-UHFFFAOYSA-N 0.000 description 1
- WUBUWBUVAKMGCO-UHFFFAOYSA-N morusin Natural products CC(=CCC1=C(Cc2c3C=CC(C)(C)Oc3cc(O)c2C1=O)c4ccc(O)cc4O)C WUBUWBUVAKMGCO-UHFFFAOYSA-N 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920006122 polyamide resin Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/488—Pueraria (kudzu)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
- A61K36/605—Morus (mulberry)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了一种用于治疗高血脂症及动脉粥样硬化的药物组合物,所述药物组合物包含:活性组分,所述活性组分为葛根素、大豆苷、染料木苷、大豆苷元、毛蕊异黄酮葡萄糖苷、黄芪皂苷II、黄芪甲苷、芒柄花黄素、桑皮苷A、桑辛素、东莨菪内酯、桑根酮C、1‑脱氧野尻霉素、葛根多糖、黄芪多糖、桑白皮多糖中的两种或两种以上的组合;和药学上可接受的载体。本发明的药物组合物,可以降低动脉粥样硬化模型apoE‑/‑转基因小鼠的主动脉中脂肪斑块面积,并且具有调节小鼠高血脂作用,能够治疗高血脂症及动脉粥样硬化。
Description
技术领域
本发明涉及一种用于治疗高血脂症及动脉粥样硬化的药物组合物及其制备方法和用途。更具体地,本发明涉及葛根、黄芪及桑白皮药材中的有效成分的复方药物组合物,及其在制备治疗高血脂症及动脉粥样硬化药物中的用途。
背景技术
动脉粥样硬化(atherosclerosis,AS)是一种慢性动脉疾病,可引起冠心病、心肌梗死等心脑血管病以及中风等,病死率和致残率较高,是严重危害人类健康的常见病、多发病。在发达国家以及一些发展中国家,动脉粥样硬化性心血管疾病的发病率呈逐年上升趋势,已成为多种中老年常见病的基础病变,被称为“头号杀手”。AS病变部位主要发生于大、中动脉内膜,多由脂肪的代谢紊乱、神经血管的功能失调引起,在内膜上出现胆固醇、类脂肪等黄色粥样斑块物质。AS的发病机制非常复杂,血脂代谢异常和炎症被认为是最主要的两个致病因素。由于脂代谢紊乱导致血脂水平异常增高是AS的重要基础,积极预防和控制AS的血脂代谢异常具有重要意义。目前降血脂类的药物在临床治疗AS上应用非常广泛,常用药物有贝特类、烟酸类、胆固醇合成抑制剂和他汀类药物等。以上药物作用机制明确但作用效果单一,且多数存在价格较高、副作用明显及停药后容易反弹等缺点。
鉴于AS的发病机制尚十分复杂,涉及脂质代谢异常、炎症、血管内皮细胞损伤、平滑肌细胞和胶原增殖、泡沫细胞形成、血小板黏附聚集、障碍等多个方面。且AS属于慢性疾病,需要长期用药,化学药物虽在临床上取得了一定成效,但很难从根本上预防AS的发生发展,且治疗费用昂贵,副作用明显,患者的依从性低影响药物的疗效,从而制约着其在临床上的普及应用。
中医药可通过多途径、多环节、多靶点治疗疾病,且不良反应轻,耐受性好,对于复杂疾病的治疗具有独特优势。目前,不少抗动脉粥样硬化的中医药类药物已在临床上使用,如心脑康、脑心舒、月见草和银杏制剂等,其主要能发挥调节血脂、防治血栓形成等作用。但存在药效物质基础不明,制剂质量可控性较差,且大多缺乏对照研究等问题。因此,迫切需要开发新的成分明确、质量可控、疗效显著的抗AS药物。
发明内容
本发明的目的在于提供一种成分明确、质量可控、疗效显著的治疗高血脂症及动脉粥样硬化的药物组合物。
本发明的第一方面,提供一种药物组合物,所述药物组合物包含活性组分,所述活性组分为葛根素、大豆苷、染料木苷、大豆苷元、毛蕊异黄酮葡萄糖苷、黄芪皂苷II、黄芪甲苷、芒柄花黄素、桑皮苷A、桑辛素、东莨菪内酯、桑根酮C、1-脱氧野尻霉素、葛根多糖、黄芪多糖、桑白皮多糖中的两种或两种以上的组合。
在另一优选例中,所述活性组分为葛根素、大豆苷、染料木苷、大豆苷元、毛蕊异黄酮葡萄糖苷、黄芪皂苷II、黄芪甲苷、芒柄花黄素、桑皮苷A、桑辛素、东莨菪内酯、桑根酮C、1-脱氧野尻霉素、葛根多糖、黄芪多糖、桑白皮多糖中的3-16种(较佳4-15、5-12或6-14种)的组合。
在另一优选例中,所述药物组合物含有0.001~99wt%,较佳地0.1~90wt%,更佳地1~80wt%的活性组分,按药物组合物的总重量计。
在另一优选例中,所述药物组合物为片剂、胶囊制剂、颗粒剂、丸剂、口服液或注射剂形式。
在另一优选例中,所述活性组分提取自葛根、黄芪和/或桑白皮药材。
在另一优选例中,所述活性组分为1-30重量份葛根素、1-15重量份大豆苷、0.5-10重量份染料木苷、0.5-15重量份大豆苷元、0.5-10重量份毛蕊异黄酮葡萄糖苷、0.5-10重量份黄芪皂苷II、0.5-10重量份黄芪甲苷、0.5-10重量份芒柄花黄素、0.5-10重量份桑皮苷A、0.5-10重量份桑辛素、0.5-10重量份东莨菪内酯、0.5-10重量份桑根酮C、0.5-10重量份1-脱氧野尻霉素、5-200重量份葛根多糖、5-200重量份黄芪多糖、5-200重量份桑白皮多糖中的两种或两种以上的组合。
在另一优选例中,所述活性组分为1-20重量份葛根素、1-15重量份大豆苷、0.5-2重量份染料木苷、0.5-15重量份大豆苷元、0.5-2重量份毛蕊异黄酮葡萄糖苷、0.5-2重量份黄芪皂苷II、0.5-5重量份黄芪甲苷、0.5-2重量份芒柄花黄素、0.5-2重量份桑皮苷A、0.5-2重量份桑辛素、0.5-2重量份东莨菪内酯、0.5-5重量份桑根酮C、0.5-5重量份1-脱氧野尻霉素、10-50重量份葛根多糖、10-80重量份黄芪多糖、15-50重量份桑白皮多糖中的两种或两种以上的组合。
在另一优选例中,所述葛根素的含量大于0.1wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述大豆苷的含量大于0.05wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述染料木苷的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述大豆苷元的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述毛蕊异黄酮葡萄糖苷的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述黄芪皂苷II的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述黄芪甲苷的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述芒柄花黄素的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述桑皮苷A的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述桑辛素的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述东莨菪内酯的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述桑根酮C的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述1-脱氧野尻霉素的含量大于0.01wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述葛根多糖的含量大于1wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述黄芪多糖的含量大于1wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,和/或
所述桑白皮多糖的含量大于1wt%,较佳为0.1-98.99wt%或0.5-95wt%或1-90wt%,
以上含量按所述的药物组合物的总重量计。
在另一优选例中,所述药物组合物还包含药学上可接受的载体。
本发明的第二方面,提供第一方面所述的药物组合物的制备方法,所述制备方法包括以下步骤:
i)提供活性组分,所述活性组分如第一方面所述;
ii)将步骤i)获得的所述活性组分进行混合得到所述药物组合物。
在另一优选例中,所述活性组分从葛根、黄芪和/或桑白皮药材中提取。
本发明的第三方面,提供第一方面所述的药物组合物的用途,其特征在于,所述药物组合物用于:
(1)制备预防和/或治疗高血脂症的药物;或
(2)制备预防和/或治疗动脉粥样硬化的药物。
本发明的药物组合物,可以降低动脉粥样硬化模型apoE-/-转基因小鼠的主动脉中脂肪斑块面积,并且具有调节小鼠高血脂作用,能够治疗高血脂症及动脉粥样硬化。
应理解,在本发明范围内中,本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合,从而构成新的或优选的技术方案。说明书中所揭示的各个特征,可以被任何提供相同、均等或相似目的的替代性特征取代。限于篇幅,在此不再一一累述。
附图说明
图1为主动脉整体油红染色结果图。
具体实施方式
本申请的发明人经过广泛而深入地研究,首次研发出一种成分明确、质量可控的药物组合物,其包含的有效活性成分可自葛根、黄芪及桑白皮药材中提取获得,该药物组合物可以降低动脉粥样硬化模型apoE-/-转基因小鼠的主动脉中脂肪斑块面积,并且有调节小鼠高血脂作用,能够治疗高血脂症及动脉粥样硬化,疗效显著。在此基础上,完成了本发明。
本发明,涉及以下中药材:
葛根:性凉,味甘、辛。归肺、胃经。具有解肌退热,透疹,生津止渴,升阳止泻等功效。用于表证发热,项背强痛,麻疹不透,热病口渴,阴虚消渴,热泻热痢,脾虚泄泻等症。
黄芪:甘,微温。归肺、脾经。具有补气固表,利尿托毒,排脓,敛疮生肌等功效。用于气虚乏力,食少便溏,中气下陷,久泻脱肛,便血崩漏,表虚自汗,气虚水肿,痈疽难溃,久溃不敛,血虚痿黄,内热消渴等症。
桑白皮:甘,寒。归肺经。具有泻肺平喘,利水消肿等功效。用于肺热喘咳,水肿胀满尿少,面目肌肤浮肿等症。
如本文所用,术语“有效活性成分”指葛根、黄芪及桑白皮药材中的有效成分,包括:葛根素、大豆苷、染料木苷、大豆苷元、毛蕊异黄酮葡萄糖苷、黄芪皂苷II、黄芪甲苷、芒柄花黄素、桑皮苷A、桑辛素、东莨菪内酯、桑根酮C、1-脱氧野尻霉素、葛根多糖、黄芪多糖、桑白皮多糖。
在本发明中,除了使用上述有效活性成分之外,还可以使用所述有效活性成分的盐,例如药学上可接受的盐酸盐、硫酸盐、乙酸盐、甲磺酸盐等。
如本文所用,术语“包括”包括了“含有”、“基本上由……构成”和“由……构成”。
如本文所用,术语“基本上由……构成”指在药物组合物中,除了含有有效活性成分或辅助成分之外,还可含有少量的且不影响有效成分的次要成分和/或杂质。例如,可以含有甜味剂以改善口味、抗氧化剂以防止氧化,以及其他本领域常用的添加剂。通常葛根素、大豆苷、染料木苷、大豆苷元、毛蕊异黄酮葡萄糖苷、黄芪皂苷II、黄芪甲苷、芒柄花黄素、桑皮苷A、桑辛素、东莨菪内酯、桑根酮C、1-脱氧野尻霉素、葛根多糖、黄芪多糖、桑白皮多糖占全部药物组合物重量的0.01-99%。
如本文所用,术语“药学上可接受的载体”指用于治疗剂给药的载体,包括各种赋形剂、佐剂、稀释剂或其组合。该术语指这样一些药剂载体:它们本身并不是必要的活性成分,且施用后没有过分的毒性。合适的载体是本领域普通技术人员所熟知的。在Remington's Pharmaceutical Sciences(Mack Pub.Co.,N.J.1991)中可找到关于药学上可接受的赋形剂的充分讨论。在组合物中药学上可接受的载体可含有液体,如水、盐水、甘油和乙醇。另外,这些载体中还可能存在辅助性的物质,如润湿剂或乳化剂、pH缓冲物质等。来自于葛根、黄芪及桑白皮的除有效活性成分之外的非必要成分,以及其他非必要成分(例如其他辅助性药材),也包括在药学上可接受的载体的定义中。
如本文所用,术语“本发明的组合物”包括药物组合物和饮食补充剂,只要它们含有或基本上由葛根素、大豆苷、染料木苷、大豆苷元、毛蕊异黄酮葡萄糖苷、黄芪皂苷II、黄芪甲苷、芒柄花黄素、桑皮苷A、桑辛素、东莨菪内酯、桑根酮C、1-脱氧野尻霉素、葛根多糖、黄芪多糖、桑白皮多糖等活性成分构成。通常,上述活性成分的重量占组合物总重量的0.01-99%。
此外,本发明组合物可含有治疗高血脂症及动脉粥样硬化的其他物质。
本发明药物组合物对高血脂症及动脉粥样硬化的治疗效果与有效活性成分的含量密切相关。研究表明,为了取得稳定的治疗效果,应使药物组合物中有效活性成分含量达到一定的范围,例如,葛根素的含量大于0.1wt%;大豆苷的含量大于0.05wt%;染料木苷的含量大于0.01wt%;大豆苷元的含量大于0.01wt%;毛蕊异黄酮葡萄糖苷的含量大于0.01wt%;黄芪皂苷II的含量大于0.01wt%;黄芪甲苷的含量大于0.01wt%;芒柄花黄素的含量大于0.01wt%;桑皮苷A的含量大于0.01wt%;桑辛素的含量大于0.01wt%;东莨菪内酯的含量大于0.01wt%;桑根酮C的含量大于0.01wt%;1-脱氧野尻霉素的含量大于0.01wt%;葛根多糖的含量大于1wt%;黄芪多糖的含量大于1wt%;桑白皮多糖的含量大于1wt%;
除了按必要活性成分来限定本发明的组合物之外,还可用必要组份(药材)的配比来限定本发明的药物组合物。
在一优选实施方式中,本发明组合物中,按重量计,有效活性成分的合适配比是:
余量的物质是药学上可接受的载体,例如淀粉、麦芽糊精等。
本发明的药物组合物或饮食补充剂,可以通过常规方法制成任何常规的制剂形式,优选的是片剂、胶囊制剂、颗粒剂、丸剂、口服液、注射剂等。
本发明药物组合物进行了动物试验,对该药投入治疗疾病的使用环节提供了科学而客观的依据。其试验结果表明该药物组合物对动脉粥样硬化apoE-/-转基因小鼠模型,可以降低小鼠的主动脉中脂肪斑块面积,并且有调节小鼠高血脂作用。
本发明的优点在于:
(1)配制简便、活性成分明确且针对性强;
(2)对活性成分可进行定量控制,从而保证质量;
(3)成本低廉;
(4)疗效显著,安全性高。
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件(如Sambrook等人,分子克隆:实验室手册(New York:Cold Spring Harbor LaboratoryPress,1989)中所述的条件)或按照制造厂商所建议的条件。除非另外说明,否则百分比和份数是重量百分比和重量份数。
除非另行定义,文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
制备实施例1
称取葛根200g,黄芪100g及桑白皮100g,加入8倍量的水,浸泡30分钟后,水煎煮提取2次,每次煎煮时间为2小时,2次提取液合并,过滤,减压浓缩至相对密度为1.27(55℃),稠膏烘干粉碎,得提取物。
制备实施例2
称取葛根100g和黄芪200g,加入10倍量的水,浸泡30分钟后,水煎煮提取2次,每次煎煮时间为1.5小时,2次提取液合并,过滤,减压浓缩至相对密度为1.26(55℃),稠膏烘干粉碎,得提取物。
制备实施例3
葛根素的制备
葛根药材800g,加入8倍量50%乙醇溶液加热回流提取2次,每次1.5h,合并提取液过滤,滤液减压回收乙醇,继续减压浓缩至800ml,将浓缩后的提取液上样于AB-8型大孔树脂,静止吸附3h,用去离子水洗至无色,再用4倍柱体积的70%乙醇洗脱,收集70%乙醇洗脱液,减压浓缩。对上述浓缩后的浸膏采用硅胶柱层析分离,以二氯甲烷与甲醇按1:0~0:1的体积比形成的混合溶液进行梯度洗脱,薄层层析检测,收集含有葛根素的馏分。以上葛根素的馏分再经Sephedex LH-20凝胶色谱分离纯化,得葛根素。
制备实施例4
大豆苷的制备
葛根药材1kg,加入8倍量60%乙醇溶液加热回流提取2次,每次1h,合并提取液过滤,滤液减压回收乙醇,继续减压浓缩至1000ml,将浓缩后的提取液上样于D101型大孔树脂,先用4倍柱体积的蒸馏水进行洗涤,然后用5倍柱体积的40%的乙醇溶液洗脱,收集40%乙醇洗脱液,减压浓缩得浸膏。对上述浓缩后的浸膏采用硅胶柱层析分离,二氯甲烷-甲醇梯度洗脱,分部收集馏分,薄层层析检测,合并含有大豆苷的馏分。再以甲醇对其进行重结晶,得大豆苷。
制备实施例5
染料木苷的制备
葛根药材1kg,加入8倍量70%乙醇溶液加热回流提取2次,每次1.5h,合并提取液,减压回收乙醇,继续减压浓缩至1200ml。上述浓缩后的提取液上样于HP-20型大孔树脂,先用5倍柱体积的蒸馏水进行洗涤,然后用6倍柱体积的50%的乙醇溶液洗脱,收集50%乙醇洗脱液,减压浓缩得浸膏。对上述浓缩后的浸膏采用硅胶柱层析分离,二氯甲烷-甲醇梯度洗脱,分部收集馏分,薄层层析检测,合并含有染料木苷的流份。再经Sephedex LH-20凝胶色谱分离纯化,得染料木苷。
制备实施例6
大豆苷元的制备
取葛根药材1kg,加8倍量的70%乙醇回流提取,提取2次,每次1.5h,过滤后,合并提取液,滤液减压回收至无醇味后,减压浓缩至相对密度为1.19(50℃测)的稠膏。上述稠膏加2200ml 5%HCl溶液加热回流4h水解,水解液趁热过滤,待滤液冷却至室温用乙酸乙酯萃取3次,减压浓缩。对上述浓缩后的浸膏采用硅胶柱层析分离,二氯甲烷-甲醇梯度洗脱,分部收集馏分,薄层层析检测,合并含有大豆苷元的流份。再经Sephedex LH-20凝胶色谱分离纯化,得大豆苷元。
制备实施例7
毛蕊异黄酮葡萄糖苷的制备
取黄芪药材1kg,加10倍量的90%乙醇回流提取,提取2次,每次2h,过滤后,合并提取液,滤液减压回收至无醇味后,再浓缩至适量。上述浓缩液上样于D101型大孔树脂,先用水洗至流出液无色,后用4倍柱体积的20%乙醇洗脱,弃去洗脱液,再用5倍柱体积的40%的乙醇溶液洗脱,收集40%乙醇洗脱液,减压浓缩,再真空干燥。干膏加甲醇溶解,静置12小时,分离分离得沉淀,再甲醇反复重结晶,得到毛蕊异黄酮葡萄糖苷。
制备实施例8
黄芪皂苷II和黄芪甲苷的制备
取黄芪药材3kg,加10倍量的70%乙醇回流提取,提取3次,每次1.5h,过滤后,合并提取液,滤液减压回收至无醇味后,再浓缩至适量。将浓缩后的提取液上样于HPD-600型大孔树脂,先用水洗至流出液无色,后用3倍柱体积的20%乙醇洗脱,弃去洗脱液,再用5倍柱体积的70%的乙醇溶液洗脱,收集70%乙醇洗脱液,减压浓缩。对上述浓缩后的浸膏采用ODS柱分离,用甲醇-水梯度洗脱(1:5~1:1),分部收集馏分,薄层层析检测,合并相同流分。ODS柱的甲醇-水(1:4)洗脱流分合并后再经Sephedex LH-20凝胶色谱分离纯化,得黄芪甲苷。ODS柱的甲醇-水(1:2)洗脱流分合并后再经硅胶柱层析分离,二氯甲烷-甲醇(9:1)洗脱,得黄芪皂苷II。
制备实施例9
芒柄花黄素的制备
取黄芪药材2kg,加10倍量的70%乙醇回流提取,提取2次,每次2h,过滤后,合并提取液,滤液减压回收至无醇味后,继续浓缩至适量。上述浓缩液用石油醚萃取3次,除去石油醚萃取液,剩余水相经氯仿萃取3次,合并氯仿萃取液,回收至干。氯仿部位经反复硅胶柱层析分离,二氯甲烷-甲醇梯度洗脱,分部收集馏分,薄层层析检测,合并含有芒柄花黄素的流份。再经Sephedex LH-20凝胶色谱分离纯化,得芒柄花黄素。
制备实施例10
桑皮苷A的制备
取桑白皮药材2kg,加8倍量的70%乙醇回流提取,提取2次,每次2h,过滤后,合并提取液,滤液减压回收至无醇味后,继续浓缩至适量。将浓缩后的提取液上样于D101型大孔树脂,先用水洗至流出液无色,后用5倍柱体积的40%乙醇洗脱,收集40%乙醇洗脱液,减压浓缩。对上述浓缩后的浸膏反复硅胶柱层析分离,二氯甲烷-甲醇梯度洗脱,分部收集馏分,薄层层析检测,合并含有桑皮苷A的流份。再经Sephedex LH-20凝胶色谱分离纯化,得桑皮苷A。
制备实施例11
桑辛素的制备
取桑白皮药材2.5kg,加8倍量的60%乙醇回流提取,提取2次,每次2h,过滤后,合并提取液,滤液减压回收至无醇味后,继续浓缩至适量。将浓缩后的提取液上样于HPD-400型大孔树脂,先用水洗至流出液无色,后用5倍柱体积的60%乙醇洗脱,收集60%乙醇洗脱液,减压浓缩。上述浓缩液再加入聚酰胺树脂中吸附,用5倍柱体积30%甲醇杂质,再用6倍体积60%甲醇洗脱,收集60%乙醇洗脱液,减压浓缩成浸膏。对上述浓缩后的浸膏反复硅胶柱层析分离,石油醚-丙酮梯度洗脱,分部收集馏分,薄层层析检测,合并含有桑辛素的流份。再经SephedexLH-20凝胶色谱分离纯化,得桑辛素。
制备实施例12
东莨菪内酯的制备
取桑白皮药材2kg,加8倍量的70%乙醇回流提取,提取2次,每次2h,过滤后,合并提取液,滤液减压回收至无醇味后,继续浓缩至适量。上述浓缩液用氯仿萃取3次,合并氯仿萃取液,回收至干。对上述浓缩后的浸膏反复硅胶柱层析分离,二氯甲烷-甲醇梯度洗脱,分部收集馏分,薄层层析检测,合并含有东莨菪内酯的流份。再经Sephedex LH-20凝胶色谱分离纯化,得东莨菪内酯。
制备实施例13
桑根酮C的制备
取桑白皮药材2kg,加8倍量的90%乙醇回流提取,提取2次,每次2h,过滤后,合并提取液,滤液减压回收至无醇味后,继续浓缩至适量。将浓缩后的提取液上样于AB-8型大孔树脂,先用水洗至流出液无色,后用6倍柱体积的40%乙醇洗脱,弃去洗脱液,再用5倍柱体积的60%的乙醇溶液洗脱,收集60%乙醇洗脱液,减压浓缩。对上述浓缩后的浸膏反复硅胶柱层析分离,石油醚-丙酮梯度洗脱,分部收集馏分,薄层层析检测,合并含有桑根酮C的流份。再经Sephedex LH-20凝胶色谱分离纯化,得桑根酮C。
制备实施例14
1-脱氧野尻霉素的制备
取桑白皮药材2kg,加10倍量的70%乙醇回流提取,提取2次,每次2h,过滤后,合并提取液,滤液减压回收至无醇味后,继续浓缩至适量。将浓缩后的提取液上样于AB-8型大孔树脂,先用水洗至流出液无色,后用6倍柱体积的60%乙醇洗脱,收集60%乙醇洗脱液,减压浓缩。对上述浓缩后的浸膏采用ODS柱分离,用甲醇-水梯度洗脱(1:5~1:1),分部收集馏分,薄层层析检测,合并相同流分。ODS柱的甲醇-水(2:3)洗脱流分合并后再经SephedexLH-20凝胶色谱分离纯化,得1-脱氧野尻霉素。
制备实施例15
葛根多糖的制备
葛根药材600g,加8倍量水煎煮2次,每次2小时,合并煎液,滤过,滤液减压浓缩至相对密度为1.24(55℃),放冷,加乙醇使含乙醇量为70%,静置过夜,分离沉淀并真空干燥,粉碎,过筛,得葛根多糖。
制备实施例16
黄芪多糖的制备
黄芪药材600g,加10倍量水煎煮2次,每次1.5小时,合并煎液,滤过,滤液减压浓缩至相对密度为1.25(55℃),放冷,加乙醇使含乙醇量为70%,静置过夜,分离沉淀并真空干燥,粉碎,过筛,得黄芪多糖。
制备实施例17
桑白皮多糖的制备
取桑白皮药材500g,加8倍量水煎煮2次,每次1.5小时,合并煎液,滤过,滤液减压浓缩至相对密度为1.25(55℃),放冷,加乙醇使含乙醇量为70%,静置过夜,分离沉淀并真空干燥,粉碎,过筛,得桑白皮多糖。
制备实施例18
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素4份、大豆苷3份、黄芪多糖35份。
制备实施例19
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:大豆苷4份、黄芪多糖25份。
制备实施例20
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素10份、黄芪甲苷1份。
制备实施例21
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:大豆苷12份、黄芪甲苷2份、毛蕊异黄酮葡萄糖苷1份。
制备实施例22
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素15份、黄芪甲苷2份、毛蕊异黄酮葡萄糖苷1份。
制备实施例23
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素3份、黄芪多糖40份、桑白皮多糖30份。
制备实施例24
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素6份、大豆苷12份、黄芪多糖15份、桑白皮多糖25份。
制备实施例25
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素15份、大豆苷4份、黄芪多糖50份。
制备实施例26
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素6份、大豆苷2份、黄芪甲苷1份、毛蕊异黄酮葡萄糖苷1份、黄芪多糖30份、桑皮苷A1份、1-脱氧野尻霉素1份、桑白皮多糖25份。
制备实施例27
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素4份、大豆苷3份、大豆苷元1份、黄芪甲苷2份、黄芪皂苷II 1份、芒柄花黄素1份、桑皮苷A 1份、1-脱氧野尻霉素1份。
制备实施例28
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素8份、大豆苷5份、毛蕊异黄酮葡萄糖苷1份、黄芪皂苷II 1份、黄芪甲苷1份、桑辛素1份、1-脱氧野尻霉素1份、葛根多糖25份、黄芪多糖30份、桑白皮多糖25份。
制备实施例29
药物组合物的制备
用于治疗高血脂症及动脉粥样硬化的药物组合物,是由下列重量份数的原料制成:葛根素6份、大豆苷2份、染料木苷1份、大豆苷元1份、毛蕊异黄酮葡萄糖苷1份、黄芪皂苷II 1份、黄芪甲苷1份、芒柄花黄素1份、桑皮苷A 1份、桑辛素1份、东莨菪内酯1份、桑根酮C2份、1-脱氧野尻霉素2份、葛根多糖25份、黄芪多糖30份、桑白皮多糖25份。
药理实施例1
药物组合物对自发性动脉粥样硬化apoE-/-小鼠动脉粥硬化的影响
实验动物
自发性动脉粥样硬化apoE-/-小鼠,由常州卡文斯实验动物有限公司供应,雄性。采用上海斯莱克动脉粥样硬化小鼠专用(含0.25%胆固醇)高脂饲料饲养,对照组采用普通饲料饲养。
实验方法
动物经2周适应后,apoE-/-小鼠采用高脂饲料饲养12周。从第5周开始各组小鼠经口灌胃给予各受试样品,正常小鼠与模型对照组给予生理盐水灌胃。共给药8周,第8周给药结束后,观察各组对自发性动脉粥样硬化apoE-/-小鼠主动脉病理的影响,进行主动脉油红O整染,并采用Image-Pro Plus 6.0软件分析油红O脂滴面积百分比。
实验结果如图1和表1所示。
表1 药物组合物对apoE-/-小鼠主动脉中脂肪斑块面积的影响(整染,%)
组别 | 数量N | 主动脉中脂肪斑块面积(降幅%) |
模型对照组 | 10 | 32.1±8.3 |
制备实施例18 | 10 | 21.8±10.5(32.2%) |
制备实施例21 | 10 | 21.4±7.6*(33.3%) |
制备实施例22 | 10 | 21.0±10.7(34.7%) |
正常组 | 10 | 15.1±2.3 |
注:*p<0.05,**p<0.01vs模型对照组
结果显示,制备实施例21受试品能显著降低主动脉中脂肪斑块面积;制备实施例18和制备实施例22受试品对主动脉中脂肪斑块面积的降幅也较大。采用其他制备实施例制备的药物组合物,也能显著降低主动脉中脂肪斑块面积。
药理实施例2
药物组合物对高脂血小鼠高脂血的影响
实验动物
ICR小鼠,由上海斯莱克公司供应,性别为雄性,采用普通饲料饲养。
实验方法
动物经2周适应后,预防灌胃给药10天,末次给药后2小时,腹腔注射75%蛋黄乳(20ml/kg),动物经过夜禁食后,于注射蛋黄乳20小时摘眼球取血,离心收集血浆后测定血脂四项(甘油三酯TG、总胆固醇TC、低密度脂蛋白胆固醇LDL-C和高密度脂蛋白胆固醇HDL-C)。
实验结果如表2所示。
表2 药物组合物对高脂血小鼠血脂的影响
组别 | TG | TC | HDL-C | LDL-C |
模型组 | 7.3±5.4 | 6.1±1.7 | 2.2±0.7 | 1.7±0.5 |
辛伐他汀 | 2.7±1.8* | 4.0±1.2** | 2.9±1.1<sup>p=0.067</sup> | 1.1±0.7* |
制备实施例24 | 3.3±1.6* | 4.8±0.8* | 2.6±0.5<sup>p=0.073</sup> | 1.6±0.4 |
制备实施例25 | 3.7±2.3* | 5.1±1.7 | 2.9±0.9* | 1.6±0.8 |
制备实施例28 | 3.7±1.2* | 4.6±0.9* | 2.5±0.4 | 1.4±0.7 |
正常组 | 1.4±0.3** | 3.7±0.7** | 4.0±1.0** | 0.6±0.2** |
注:*p<0.05,**p<0.01vs模型组
结果可知,与正常组相比,模型组总胆固醇TC,低密度脂蛋白胆固醇LDL-C和甘油三酯TG均显著增加(p<0.01),高密度脂蛋白胆固醇HDL-C显著下降(p<0.01),表明造模成功。
与模型组相比,阳性药辛伐他汀可显著降低TC,LDL-C和TG(p<0.01/0.05),HDL-C增加较多(p=0.067)。制备实施例24组TC和TG显著下降(<0.05),HDL-C增加较多(p=0.073)。制备实施例25可显著降低TG(p<0.05),HDL-C显著增加(p<0.05)。制备实施例28组TC和TG显著下降(p<0.05)。
上述结果表明制备实施例24、制备实施例25和制备实施例28供试品具有显著的降血脂作用。
经检测,采用其他制备实施例制备的药物组合物,也具有显著的降血脂作用。
在本发明提及的所有文献都在本申请中引用作为参考,就如同每一篇文献被单独引用作为参考那样。此外应理解,在阅读了本发明的上述讲授内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
Claims (8)
1.一种用于治疗高血脂症及动脉粥样硬化的药物组合物,其特征在于,所述药物组合物包含活性组分,所述活性组分为:
(i) 葛根素4重量份、大豆苷3重量份、黄芪多糖35重量份的组合;
(ii) 大豆苷12重量份、毛蕊异黄酮葡萄糖苷1重量份、黄芪甲苷2重量份的组合;
(iii) 葛根素15重量份、黄芪甲苷2重量份、毛蕊异黄酮葡萄糖苷1重量份的组合;
(iv) 葛根素6重量份、大豆苷12重量份、黄芪多糖15重量份、桑白皮多糖25重量份的组合;
(v) 葛根素15重量份、大豆苷4重量份、黄芪多糖50重量份的组合;或
(vi) 葛根素8重量份、大豆苷5重量份、毛蕊异黄酮葡萄糖苷1重量份、黄芪多糖30重量份、黄芪皂苷II1重量份、黄芪甲苷1重量份、桑辛素1重量份、1-脱氧野尻霉素1重量份、葛根多糖25重量份、桑白皮多糖25重量份的组合,
其中所述活性组分从葛根、黄芪、桑白皮药材中提取。
2.如权利要求1所述的药物组合物,其特征在于,所述药物组合物含有0.001~99wt%的活性组分,按药物组合物的总重量计。
3.如权利要求1所述的药物组合物,其特征在于,所述药物组合物含有0.1~90wt%的活性组分,按药物组合物的总重量计。
4.如权利要求1所述的药物组合物,其特征在于,所述药物组合物含有1~80wt%的活性组分,按药物组合物的总重量计。
5.如权利要求1所述的药物组合物,其特征在于,所述药物组合物为片剂、胶囊制剂、颗粒剂、丸剂、口服液或注射剂形式。
6.如权利要求1所述的药物组合物,其特征在于,所述药物组合物还包含药学上可接受的载体。
7.如权利要求1所述的药物组合物的制备方法,其特征在于,所述制备方法包括以下步骤:
i) 提供活性组分,所述活性组分如权利要求1中所述;
ii) 将步骤i)获得的所述活性组分进行混合得到所述药物组合物,
其中,所述活性组分从葛根、黄芪、桑白皮药材中提取。
8.如权利要求1所述的药物组合物的用途,其特征在于,所述药物组合物用于:
(1) 制备预防和/或治疗高血脂症的药物;或
(2) 制备预防和/或治疗动脉粥样硬化的药物。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710312895.6A CN108785370B (zh) | 2017-05-05 | 2017-05-05 | 一种用于治疗高血脂症及动脉粥样硬化的药物组合物 |
PCT/CN2018/085524 WO2018202107A1 (zh) | 2017-05-05 | 2018-05-04 | 一种用于治疗高血脂症及动脉粥样硬化的药物组合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710312895.6A CN108785370B (zh) | 2017-05-05 | 2017-05-05 | 一种用于治疗高血脂症及动脉粥样硬化的药物组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108785370A CN108785370A (zh) | 2018-11-13 |
CN108785370B true CN108785370B (zh) | 2022-02-25 |
Family
ID=64016385
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710312895.6A Active CN108785370B (zh) | 2017-05-05 | 2017-05-05 | 一种用于治疗高血脂症及动脉粥样硬化的药物组合物 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN108785370B (zh) |
WO (1) | WO2018202107A1 (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110179788A (zh) * | 2019-07-03 | 2019-08-30 | 深圳市老年医学研究所 | 桑辛素在制备治疗脂肪肝药物中的应用 |
CN111004336B (zh) * | 2020-03-09 | 2020-06-12 | 江西中医药大学 | 一种葛根多糖及其制备方法和用途 |
CN116019824B (zh) * | 2023-03-29 | 2023-05-30 | 吉林华康药业股份有限公司 | 一种用于防治微循环障碍的中药组合物 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101088521B (zh) * | 2006-06-14 | 2010-10-27 | 北京四环科宝制药有限公司 | 一种黄芪药物制剂及其制备方法 |
CN101904863B (zh) * | 2009-06-04 | 2012-05-30 | 广州泽力医药科技有限公司 | 一种黄芪甲苷和黄芪多糖复配的药用组合物制备工艺 |
CN102846715A (zh) * | 2011-06-29 | 2013-01-02 | 包头市千年健药物研究开发有限公司 | 一种治疗糖尿病合并高脂蛋白血症的药物及其制作方法 |
CN102895294B (zh) * | 2012-10-30 | 2014-09-03 | 黑龙江珍宝岛药业股份有限公司 | 一种黄芪注射液及其制备方法 |
CN103301200A (zh) * | 2013-06-14 | 2013-09-18 | 包头市千年健医药科技有限公司 | 一种黄芪散药物、提取方法及用途 |
CN105726638A (zh) * | 2016-04-19 | 2016-07-06 | 北京宜生堂医药科技研究有限公司 | 一种降脂保肝组合物及其用途 |
CN106324161B (zh) * | 2016-10-24 | 2017-11-14 | 广州康臣药物研究有限公司 | 治疗糖尿病肾病的中药组合物的质量检测方法 |
CN107854522B (zh) * | 2017-09-13 | 2020-10-30 | 北京宜生堂医药科技研究有限公司 | 一种组合物及其制备方法和用途 |
-
2017
- 2017-05-05 CN CN201710312895.6A patent/CN108785370B/zh active Active
-
2018
- 2018-05-04 WO PCT/CN2018/085524 patent/WO2018202107A1/zh active Application Filing
Also Published As
Publication number | Publication date |
---|---|
WO2018202107A1 (zh) | 2018-11-08 |
CN108785370A (zh) | 2018-11-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2003202144B2 (en) | Method for processing ginseng and the uses of extract of processed ginseng | |
EP1829519B1 (en) | A pharmaceutical composition for the treatment and/or prevention of hyperlipidemia, processes for producing the same and the use thereof | |
RU2294208C2 (ru) | Применение экстракта обработанного женьшеня и выделенных из него сапонинов | |
CN101011561B (zh) | 黄连温胆汤现代中药口服制剂及其生产方法 | |
CN102670673A (zh) | 秋葵活性成分在制备防治代谢性疾病的药物中的应用 | |
CN108785370B (zh) | 一种用于治疗高血脂症及动脉粥样硬化的药物组合物 | |
WO2018133563A1 (zh) | 一种人参属植物提取物及其药物组合物和应用 | |
CN103127232A (zh) | 桑叶方总提物及其制剂和用途 | |
CN104857154A (zh) | 一种治疗“三高”症的中药组合物及其制备方法 | |
CN108143787A (zh) | 一种葛根、枳椇子复合黄酮的制备方法 | |
KR20110078525A (ko) | 인삼 열매 추출물을 함유하는 간기능 개선용 조성물 | |
KR20060000488A (ko) | 인삼 또는 홍삼 추출물, 그의 유산균 발효물 및 그의장내세균 발효물로 이루어진 군으로부터 선택된 1종이상의 인삼 추출물 소양증 예방 및 치료제 조성물 | |
CN108567914B (zh) | 一种具有改善睡眠作用的中药制剂及其制备方法和应用 | |
CN110538311A (zh) | 一种用于控制高血压的纯中药组合物及其制备方法 | |
EP2216039A1 (en) | Pharmaceutical compositions for treating anxiety | |
CN108434250B (zh) | 一种具有美容祛黄褐斑功效的阿胶口服液及其制备方法 | |
KR102282839B1 (ko) | 숙취해소 또는 개선용 조성물 | |
CN101744991B (zh) | 一种人参、麦冬、五味子的单独提取方法及其制剂 | |
CN101745012B (zh) | 一种人参/麦冬和五味子的提取方法及其制剂 | |
KR20040004241A (ko) | 인삼의 가공방법 | |
CN110368456A (zh) | 一种有助于改善睡眠的竹叶黄酮组合物 | |
CN109223739A (zh) | 一种组合物及其制备方法和应用 | |
CN115120657B (zh) | 用于烧伤休克期抗渗扩容的中药组合物及药物制剂和制备方法 | |
CN103110675A (zh) | 改善营养性贫血软胶囊及其制备方法 | |
EP4122479A1 (en) | Tranquilizing composition |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |