CN104374890A - Ilex kudingcha C. J. Tseng extract - Google Patents
Ilex kudingcha C. J. Tseng extract Download PDFInfo
- Publication number
- CN104374890A CN104374890A CN201410633217.6A CN201410633217A CN104374890A CN 104374890 A CN104374890 A CN 104374890A CN 201410633217 A CN201410633217 A CN 201410633217A CN 104374890 A CN104374890 A CN 104374890A
- Authority
- CN
- China
- Prior art keywords
- extract
- tseng
- ilex
- group
- rat
- 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
- 239000000284 extract Substances 0.000 title claims abstract description 86
- 241001545416 Ilex kaushue Species 0.000 title abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 10
- 229940079593 drug Drugs 0.000 claims abstract description 6
- 229930182470 glycoside Natural products 0.000 claims description 30
- -1 cyanogen glycosides Chemical class 0.000 claims description 26
- 235000003325 Ilex Nutrition 0.000 claims description 25
- 241000209035 Ilex Species 0.000 claims description 25
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 25
- 244000078118 Ilex latifolia Species 0.000 claims description 20
- 235000008706 Ilex latifolia Nutrition 0.000 claims description 20
- 150000007965 phenolic acids Chemical class 0.000 claims description 11
- 239000012535 impurity Substances 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 abstract description 18
- 239000008280 blood Substances 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 12
- 150000002632 lipids Chemical class 0.000 abstract description 11
- 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 abstract description 7
- 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 abstract description 7
- 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 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 6
- 231100000331 toxic Toxicity 0.000 abstract description 6
- 230000002588 toxic effect Effects 0.000 abstract description 6
- 201000005577 familial hyperlipidemia Diseases 0.000 abstract description 4
- 208000026106 cerebrovascular disease Diseases 0.000 abstract description 3
- 230000036541 health Effects 0.000 abstract description 3
- 208000024891 symptom Diseases 0.000 abstract description 3
- 206010019799 Hepatitis viral Diseases 0.000 abstract description 2
- 208000024172 Cardiovascular disease Diseases 0.000 abstract 1
- 241000700605 Viruses Species 0.000 abstract 1
- 229930182485 cyanogenic glycoside Natural products 0.000 abstract 1
- 150000008142 cyanogenic glycosides Chemical class 0.000 abstract 1
- 230000002526 effect on cardiovascular system Effects 0.000 abstract 1
- 238000007254 oxidation reaction Methods 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 241000700159 Rattus Species 0.000 description 30
- 235000013824 polyphenols Nutrition 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- 241000272525 Anas platyrhynchos Species 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000012467 final product Substances 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- UFCLZKMFXSILNL-RVXRWRFUSA-N 4,5-di-O-caffeoylquinic acid 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-RVXRWRFUSA-N 0.000 description 6
- UFCLZKMFXSILNL-UHFFFAOYSA-N NSC 649410 Natural products C=1C=C(O)C(O)=CC=1C=CC(=O)OC1C(O)CC(O)(C(O)=O)CC1OC(=O)C=CC1=CC=C(O)C(O)=C1 UFCLZKMFXSILNL-UHFFFAOYSA-N 0.000 description 6
- 239000004952 Polyamide Substances 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 6
- 102000019197 Superoxide Dismutase Human genes 0.000 description 6
- 108010012715 Superoxide dismutase Proteins 0.000 description 6
- 239000000470 constituent Substances 0.000 description 6
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 6
- 238000010253 intravenous injection Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229920002647 polyamide Polymers 0.000 description 6
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 6
- 229930182490 saponin Natural products 0.000 description 6
- 150000007949 saponins Chemical class 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 150000002338 glycosides Chemical class 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 5
- 206010003178 Arterial thrombosis Diseases 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229920002472 Starch Polymers 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 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
- 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 4
- 239000013078 crystal Substances 0.000 description 4
- 238000005520 cutting process Methods 0.000 description 4
- 229950009125 cynarine Drugs 0.000 description 4
- 238000005238 degreasing Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 230000004089 microcirculation Effects 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000004064 recycling Methods 0.000 description 4
- 239000013049 sediment Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- YDDUMTOHNYZQPO-UHFFFAOYSA-N 1,3-bis{[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-4,5-dihydroxycyclohexanecarboxylic acid Natural products OC1C(O)CC(C(O)=O)(OC(=O)C=CC=2C=C(O)C(O)=CC=2)CC1OC(=O)C=CC1=CC=C(O)C(O)=C1 YDDUMTOHNYZQPO-UHFFFAOYSA-N 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- SITQVDJAXQSXSA-CEZRHVESSA-N Cynarin Natural products O[C@@H]1C[C@@](C[C@H](O)[C@H]1OC(=O)C=Cc2ccc(O)c(O)c2)(OC(=O)C=Cc3cccc(O)c3O)C(=O)O SITQVDJAXQSXSA-CEZRHVESSA-N 0.000 description 3
- 241000725618 Duck hepatitis B virus Species 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- YDDUMTOHNYZQPO-BKUKFAEQSA-N cynarine Natural products O[C@H]1C[C@@](C[C@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)(OC(=O)C=Cc3ccc(O)c(O)c3)C(=O)O YDDUMTOHNYZQPO-BKUKFAEQSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 230000000004 hemodynamic effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 208000031225 myocardial ischemia Diseases 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 231100000572 poisoning Toxicity 0.000 description 3
- 230000000607 poisoning effect Effects 0.000 description 3
- 238000005498 polishing Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 150000003648 triterpenes Chemical class 0.000 description 3
- 235000020985 whole grains Nutrition 0.000 description 3
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- 101800004637 Communis Proteins 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 229930189092 Notoginsenoside Natural products 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229960004150 aciclovir Drugs 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000003446 pia mater Anatomy 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002000 scavenging effect Effects 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 241000209034 Aquifoliaceae Species 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
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000027691 Conduct disease Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 1
- 108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229920002292 Nylon 6 Polymers 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical group CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 210000002969 egg yolk Anatomy 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
- 238000011156 evaluation Methods 0.000 description 1
- 208000024756 faint Diseases 0.000 description 1
- 235000019197 fats Nutrition 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
- 230000004907 flux Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003502 gasoline Substances 0.000 description 1
- 230000001435 haemodynamic effect Effects 0.000 description 1
- 239000007887 hard shell capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000002955 isolation 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
- 230000031700 light absorption Effects 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 206010029864 nystagmus Diseases 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 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
- 230000009467 reduction Effects 0.000 description 1
- 230000004895 regional blood flow Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 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
- 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
- 235000005493 rutin Nutrition 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 208000011726 slow pulse Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011122 softwood Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to Ilex kudingcha C. J. Tseng leaf extract with a medical value and a preparation method thereof. The extract is characterized in that the Ilex kudingcha C. J. Tseng leaf extract is enriched with caffeoylquinic acid effective components; a toxic component, namely Ilex kudingcha C. J. Tseng cyanogenic glycoside and a bitter substance are removed; and the Ilex kudingcha C. J. Tseng extract leaf extract has the activities of resisting oxidization, lowering blood lipid, resisting viruses and the like, and can be used for producing medicines or health products for preventing and treating cardiovascular and cerebrovascular diseases, hyperlipemia symptoms and virus hepatitis.
Description
Technical field
The present invention is the divisional application of No. 201110162622.0 patented claims, and the denomination of invention of original bill No. 201110162622.0 patented claims is: a kind of Ilex kudincha C. J. Tseng extract, and the applying date is: on June 16th, 2011.The invention belongs to medicinal plant extract field, relate to Ilex kudincha C. J. Tseng extract and preparation method thereof and in preparation method and application, comprise and remove toxic ingredient Ilex Latifolia Thunb cyanogen glycosides and amaroid.
Background technology
Ilex kudincha C. J. Tseng (Ilex kudingcha C.J.Tseng) is Aquifoliaceae this plant tall, and be one of Ilex Latifolia Thunb kind that south China is conventional, ancient books supplement to the Herbal just has the record about this product lipopenicillinase: " food of a specified duration makes us thin, removes people's fat ".Past 30 Years comes, and many scholars are studied (research and development of natural products, 2005,17 (3): 366-370 to this plant; Hunan College of Traditional Chinese Medicine's journal, 2001,21 (2): 68-70).Pharmacological evaluation proves, this product water extract has anti-oxidant, hemangiectasis, hypotensive, lipopenicillinase isoreactivity, but taste is extremely bitter, and many people are difficult to accept, and this product also shows some toxicity.This plant component is quite complicated, that has reported just has the plurality of classes such as saponin(e, triterpene, sterol, volatile oil, fatty acid, amino acid, trace element, vitamin, which kind of or which composition is the main lipid lowerers effective substance of Ilex kudincha C. J. Tseng actually, and existing open source literature not yet provides clear and definite answer.Triterpene and saponin component compare and are paid attention in recent years, have some patents of invention relevant with these compositions, as CN101775061, CN101016328, CN1508149 etc.About phenolic constituent structure and the pharmacologically active then rarely seen report thereof of this plant, the toxic component about this plant is also indefinite.
Summary of the invention
An object of the present invention is the adjusting blood lipid active component of illustrating Ilex kudincha C. J. Tseng, discloses possible toxic component simultaneously, for this plant resources of rational exploitation and utilization provides scientific basis.Inventor is by a large amount of high flux screening and experimental study, finally determine that total phenolics is reducing blood lipid and antioxidation activity position, through chromatographic separation and purification and apply Modern spectroscopy technology measure molecular structure, illustrate a series of caffeoylquinic acid composition, its content is up to more than 4%, thus disclose the effective constituent physicochemical property of Ilex kudincha C. J. Tseng adjusting blood lipid first, for solid foundation has been established in extraction highway route design and quality control.
Caffeoylquinic acid in extract of the present invention all has having structure general formula (I), wherein R
1~ R
3in have 1 ~ 2 for coffee acyl, all the other are hydrogen, comprise six compounds (see following formula).Previous literature does not relate to the absolute configuration of cynarin; the present inventor applies CD exciton chirality method to obtain from Ilex kudincha C. J. Tseng 3; 4-, 3; 5-and 4; the absolute configuration of 5-bis--O-caffeoyl guinic acid measures; its CD composes (-) Cotton curve that all displays are split point, shows that two coffee acyls on ring are for being rotated counterclockwise relation (accompanying drawing 1), so the absolute configuration of C-3 and C-5 is R.Concrete structure formula is as follows.
These caffeoylquinic acid compositions are known natural products, and they extensively exist in plantage, but are present in Ilex kudincha C. J. Tseng with so high content and specific ratio, one of important discovery that the present invention is unexpected and useful just.Accompanying drawing 2 is the typical HPLC chromatogram of extract of the present invention, reflects the basic situation of this total phenolics chemical composition.
In extract of the present invention 3,5-bis--O-caffeoyl guinic acid and 4,5-bis--O-caffeoyl guinic acid is principle active component, and the two content fluctuates because of factors such as the medicinal material place of production, quality, extracting method, and content sum is generally 5% ~ 95% (weight).The chemical composition of extract of the present invention is not limited in above-mentioned caffeoyl guinic acid, inventor finds, natural caffeoylquinic acid C-7 carboxyl is all free, but because of contact alcohols solvent in extraction and isolation process, as ethanol, methyl alcohol, a small amount of esterification products can be caused to be formed, this kind of secondary metabolite in total phenolic acid extract usually seldom, also similar before biologically active and esterification.Inventor also finds, containing micro-flavones ingredient in phenolic acid, is Quercetin and glycoside thereof, as rutin.In addition, as shown in Figure 2, some micro constitutent is also had to need to be illustrated further in extract.
Inventor finds simultaneously, and Ilex kudincha C. J. Tseng water soluble part taste is extremely bitter, and toxicity is obvious, wherein containing saponin component known in a large number.Particularly be surprised to find that, water soluble part is in a large number containing a kind of cyanogen glycoside material, and its structure is through being accredited as noval chemical compound---and Ilex Latifolia Thunb cyanogen glycosides (ilexkudinin), this product is white crystals, and molecular weight is 313.31, and molecular formula is C
14h
19nO
7, fusing point 164 ~ 165 DEG C,
-208 ° of UV λ max 259nm.Analyze (accompanying drawing 3) through X-ray single crystal diffraction and determine structural formula following (II):
The preparation method of Ilex Latifolia Thunb cyanogen glycosides: get Ilex kudincha C. J. Tseng leaf 1kg, extract three times by 95% reflow of alcohol, merge extract, reduced pressure concentration, medicinal extract adds 5 times of water gaging stirring and dissolving, and filter, clear liquid adds 5% hcl acidifying to pH 2, filters, filtrate 5%Na
2cO
3neutralization, reduced pressure concentration, upper macroporous resin column absorption, first washes with water, then washes with 30% alcohol, collect 30% alcohol elution fraction, reduced pressure concentration, then use high pressure preparative C
18post (10 μm, 40 × 250mm) is separated, determined wavelength 254nm, flow velocity 80ml/min, eluant, eluent is ultrapure water, collecting efflux, being merged by same unimodal flow point, reduced pressure concentration according to going out peak situation, placement is spent the night, and obtains white crystals 1.3g, is Ilex Latifolia Thunb cyanogen glycosides.
Adopt improvement karber's method to the acute LD of mouse stomach Ilex Latifolia Thunb cyanogen glycosides
50measure, method: only get mouse 5O, body weight 20 ± 2g, male and female half and half, are divided into 5 groups at random, 1O/group.By geometric progression increase and decrease, 5 dosage groups are set, adjacent two dose ratio 1:0.846.Gavage respectively various dose Ilex Latifolia Thunb cyanogen glycosides (300.0,253.8,214.7,181.6,153.6mg/kg).Observe clinical symptoms and death condition every day, continuous 1 week, result showed, Ilex Latifolia Thunb cyanogen glycosides is to the LD of Mouse oral
50for 185.2mg/kg.After Ilex Latifolia Thunb cyanogen glycosides is poisoning, liver and renal index raise, and main pathology is changed to liver and the obvious enlargement of kidney, and renal cells swelling and degeneration, part renal cells breaks.This experimental result shows, after Mouse oral Ilex Latifolia Thunb cyanogen glycosides is poisoning, liver and kidney are by infringement to a certain extent.
Known, cyanogen glycoside is that plantage common are malicious component type, this constituents through animal is oral enter alimentary canal after, can decompose the hydrogen cyanide producing severe toxicity, cryanide ion enters after blood can rapidly and the prothetic group Fe of oxidized form cytochrome oxidase
3+ions binding, makes it lose the effect of transmitting hydrogen atom electronics and activating molecules oxygen, causes histanoxia and suffocate.Poisoning normal in acute attack, fast person is dead within half an hour, and symptom generally proceeds to slow pulse immediately by excited, expiratory dyspnea, and pupil expands, nystagmus, muscle cramp and convulsions and dead.50mg hydrogen cyanide gets final product causing death.Therefore, cyanogen glycosides may be main toxic ingredient known so far in Ilex kudincha C. J. Tseng.The limit detection objectionable impurities that is found to be of this cyanogen glycosides provides clear and definite index components, to ensureing that the security tool of Ilex kudincha C. J. Tseng extract is of great significance.In total phenolic acid extract of the present invention the actual content of Ilex Latifolia Thunb cyanogen glycosides all≤0.2% (weight), this residual quantity can not work the mischief to health.The HPLC chromatogram (accompanying drawing 5) of contrast Ilex kudincha C. J. Tseng Leave extract and total phenolic acid extract can be found out, the former is only second to 3,5-and 4,5-DCQA by the peak area of Ilex Latifolia Thunb cyanogen glycosides, one of three main peaks, and the substantially not aobvious Ilex Latifolia Thunb cyanogen glycosides chromatographic peak of the latter.
Two of object of the present invention is to provide a kind of preparation method of Ilex kudincha C. J. Tseng total phenolics active component.Inventor is based on the full appreciation to this plant chemical ingredient, utilize the physicochemical property difference of other composition such as caffeoylquinic acid and saponin(e, cyanogen glycosides, carbohydrate, pigment, triterpene, find out a unique syntheti c route, as shown in Figure 4, simple, be suitable for commercial production, it is characterized in that partly or entirely containing following in-sequence operational step:
A. get Ilex kudincha C. J. Tseng leaf, extract with water, alcohol or methanol eddy, filter, concentrated, obtain medicinal extract;
B. get medicinal extract, be dissolved in water, adjust pH6.5 ~ 8.5 with buck, filter, filtrate adds sour water again and is acidified to pH1 ~ 4, filters, and precipitation washes sour water, drains, obtains sediment fraction;
C. the phenolic constituent of dissolved in filtrate is adsorbed by polyamide column, first washes the removal of impurity with water, then uses the alcohol of 20% ~ 95% (weight) concentration to be washed down by phenolic constituent, recycling design, and concentrate is incorporated to sediment fraction;
D. alkanes organic solvent degreasing is used after precipitation drying;
E. precipitation Solvent Extract methods, filters, concentrated, obtains smart cream (free total phenolics);
F. smart cream buck dissolves, and filters, concentrated, dry, obtains total phenolics sodium salt.
Step a solvent for use, preferred concentration is the alcohol of 20% ~ 95% (weight); Step b and f buck used is the aqueous solution of inorganic base, preferably containing the alkali of sodion, as NaOH, sodium carbonate or sodium bicarbonate aqueous solution; Sour water used is inorganic acid aqueous solution, as sulfuric acid or salt aqueous acid; Degreasing alkane solvents used is one of sherwood oil, gasoline, hexane, cyclohexane or potpourri, preferred sherwood oil.Step e organic solvent used is ethyl acetate, acetone, normal butyl alcohol, the one of ethanol or its mixed solvent, preferred acetone and ethyl acetate, more preferred acetone.
The alternative repetitive operation of above-mentioned steps b ~ f, to reach the object of further polishing purification.Polyamide column absorption described in step c, can be recycled and reused for the purifying of total phenolics, particularly enrichment dicaffeoylquinic acid.With water or concentration, the Diluted Alcohol below 10% can first elute usually for non-phenolic constituent and single caffeoylquinic acid, and cynarin is obtained more firm by polycaprolactam, the alcohol wash-out of general working concentration more than 20%.Gained phenolic acid is not containing saponin(e and the poisonous cyanogen glycosides of hemolytic, and cynarin content is high, and 3,5-and 4,5-DCQA content sum can reach 40% ~ 90% (weight), and quality is easy to control, security is good, is suitable for as injection bulk drug.
Three of the object of the invention is to provide the medical usage of said extracted thing.After determining that total phenolics is the blood lipid-lowering active fractions of Ilex kudincha C. J. Tseng, inventor attempts having carried out the more test of pesticide effectiveness to it, be surprised to find, this extract demonstrates excellent result for the treatment of to ischemic angiocardiopathy and cerebrovascular disease, there is the obvious characteristic of high-efficiency low-toxicity, and treatment virus hepatitis and scavenging free radicals, anti-oxidant in also have performance out of the ordinary.The part the pharmacological results of extract of the present invention is provided below.
1. on the impact of focal cerebral ischemia
Rat vein infusion extract (total phenolics salt), observe this product to the behavior of rats with cerebral ischemia and the impact of infarct size caused by ferric trichloride, result shows, rat infusion extract 2,4, after 8mg/kg, animal behavior change and infarction size compare with saline control group and have clear improvement, and after 24h, behavior scoring reduces 46.2% (p<0.01), 60.1% (p<0.001), 50.8% (p<0.001) respectively; Cerebral infarct size on average reduces 20.2% (p>0.05), 50.5% (p<0.001), 41.4% (p<0.01).
2. on the impact of Rats with Microcirculation Disturbance pia mater regional blood flow
Venoclysis extract (total phenolics salt), observes the impact of this product on rat microcirculation disorder caused by macromolecule right rotary glycoside.Result shows, without obviously changing in sham-operation rat's cerebral pia mater local flow 60min; After intravenous injection macromolecule right rotary glycoside, rat brain mantle local flow obviously reduces, maximum decline 23.5 ± 6.2PU in 60min; Quiet note extract 2,4,8mg/kg group 10min after administration, namely rat brain mantle flow decreasing value is obviously less than solvent control group, more than effect lasts 60min, in 60min maximum decline be respectively 18.1 ± 7.5,18.1 ± 5.5,13.4 ± 5.5PU, compare with the maximum drop-out value of solvent control group, p respectively >0.05, <0.05, <0.001, illustrates that giving extract can alleviate the minimizing that quiet note macromolecule right rotary glycoside causes microcirculation flow.
3. on the impact of Rats with Microcirculation Disturbance blood viscosity
After last experiment terminates, get blood from rat aorta, by volume 3.8% sodium citrate is added anti-freezing in whole blood by 1:9 ratio, with cone-plate type blood viscometer (7.5 ~ 150s under different cutting speed
-1) measure rat whole blood viscosity.Result shows, compares with sham-operation group, moulding group rat after intravenous injection macromolecule right rotary glycoside under different cutting speed blood viscosity all apparently higher than normal rat.To give after extract (total phenolics salt) 2mg/kg under each cutting speed rat serum viscosity and model control group without significant difference; Give after 4mg/kg at low shear rate (7.5s
-1) time blood viscosity be starkly lower than model control group (p<0.05); After giving 8mg/kg, under each cutting speed, rat serum viscosity is all starkly lower than model control group.
4. on the impact of Rat Experimental Arterial thrombosis
Get Wistar rat, by body weight random packet, often organize 10.Control rats intravenous injection physiological saline; The quiet note extract of administration group (total phenolics salt) 2,4,8mg/kg, administration volume is 0.1ml/100g.During experiment, lumbar injection 20% urethane 1g/kg anaesthetizes, dorsal position is fixed, be separated arteria carotis communis, the stimulating electrode and the temp probe that experimental thrombus in vivo are formed instrument are hung on arteria carotis communis, and after administration, 10min starts to stimulate, and stimulus intensity is 2mA, close after stimulating 5min and stimulate switch, take off electrode, after 3min, regulate temp controlled meter to zero-bit, the record Arterial thrombosis time.Result shows, the quiet note extract of rat 2,4, after 8mg/kg, compare with control group, the Arterial thrombosis time postpones 9% (p>0.05), 63% (p<0.001), 108% (p<0.001) respectively, shows that the middle and high dosage of extract can obviously postpone the Rat Experimental Arterial thrombosis time.
5. antiplatelet aggregative activity
Get Wistar rat, by body weight random packet, often organize 10.The quiet note physiological saline of control rats, administration group respectively quiet note extract (total phenolics salt) 2,4,8mg/kg, administration volume is 0.1ml/100g.During experiment, lumbar injection 20% urethane 1g/kg anaesthetizes, dorsal position is fixed, abdominal aortic blood, 3.8% sodium citrate and whole blood are by 1:9 mixing anti-freezing, 1000rpm is centrifugal, and 7min prepares platelet rich plasma, 3000rpm is centrifugal, and 10min prepares platelet poor plasma, applying PPP self-poise platelet aggregation instrument, the physiological saline group platelet aggregation percentage of being induced by each derivant is adjusted to about 60%, and derivant ADP, arachidonic acid (AA), collagen final concentration are respectively 4 μm of ol/L, 2mmol/L, 20mg/ml.Observe the impact on the effect of administration group rat platelet aggregation.The results are shown in Table 1.
Table 1 extract of the present invention is on the impact (X ± SD, n=10) of rat platelet aggregation function
Note: compare with control group, * p<0.05; * p<0.01
6. acute toxicity test
Get female, male each 50 of body weight 18 ~ 22g Kunming mouse, each 5 groups are divided into respectively at random by sex, body weight, often organize 10, intravenous injection extract (total phenolics salt) 2070,1863,1677,1509,1358mg/kg, adjacent two dosage group agent distances are 0.9, quiet injection body is long-pending is 0.1ml/10g body weight, observes the toxic reaction of mouse in a week after administration, dead distribution and dead animal number, and presses Bliss method calculating LD
50and 95% fiducial limit.Result shows, after high dose intravenous injection extract, mouse about 1min occurs that autonomic activities reduces, and reposes, is short of breath, then occur conduct disorder, faints from fear, and about 5 ~ 20min is dead.Not dead animal breathes and recovers normal gradually after 30min, and after 1h, behavior etc. all recover normally, all no longer to occur death in later 6 days.The main organs no abnormality seen such as the dead mouse gross necropsy heart, lung, liver.Female mice LD
50be 1666.65 (1556.12 ~ 1785.33) mg/kg; Male mice LD
50be 1740.76 (1614.34 ~ 1862.56) mg/kg, female animals LD
50approximate, no significant difference.
7. the therapeutic action of pair dog myocardial ischemia and hemodynamic effects
Venoclysis extract (total phenolics salt) 2,4mg/kg, obviously improve Acute Myocardial Ischemia Tissues degree caused by ligation dog anterior descending coronary, reduce myocardial infarct size.Open chest anesthetized cardiac hemodynamics of dogs test findings shows, infusion compositions 1,2mg/kg have no significant effect each index of haemodynamics; 4mg/kg can reduce blood pressure, the maximum rate of change of left indoor pressure, left room acting and coronary resistance, on other hemodynamic parameters such as heart rate, left room EDP, total peripheral resistance, cardiac pumping functions without impact, show that extract passes through to alleviate cardiac afterload, coronary artery dilating and peripheral vascular, reduce returned blood volume and heart acting plays function of resisting myocardial ischemia.
8. on the impact of hyperlipidemia rats serum lipid level
Select SD rat (180 ~ 200g) 80, male and female half and half, feed basal feed 5d, survey serum total cholesterol (TC), triglyceride (TG) normal value, then five groups are divided at random, i.e. model group with hyperlipemia, Clofibrate group (positive controls) and the high, medium and low dosage group of extract, give high lipid food and feed.High lipid food is filled a prescription: 79% basal feed, 1% cholesterol, 10% yolk powder, 10% lard.Continuous high lipid food feeds 10d, gets hematometry TC value, proves all to form hyperlipidemia, each group selection 10 continues high lipid food and feeds, and gives relative medicine (NS suspension, 10ml/kg) respectively, model group gives isometric(al) NS, and equal gavage gives.Every day 1 time, get blood respectively in 14d and 28d from orbital venous plexus, survey TC, TG by enzyme reagent end-point method, obtained experimental data POMS-05 (random variance analysis) software statistics process, represents with x ± s.The results are shown in Table 2.
Table 2. extract of the present invention is on the impact (x ± s, n=10) of hyperlipemia rat TC and TG
Note: compare with high blood lipid model group, * p<0.05, * * p<0.01.
Data show, the high, medium and low dosage of extract all obviously can reduce hyperlipemia rat serum TC and TG level, and in dose-effect relationship, and under middle and high dosage conditions, effect is obviously better than positive drug control group.
9. lumbar injection and oral administration in duck body to the result for the treatment of of duck hepatitis B virus infection
Experiment employing one age in days Beijing duck, through leg shin intravenous injection DHB, start to duck lumbar injection and oral extract 3 dosage groups after 7 days, lumbar injection is 10,20,30mg/kg, oral administration is 30,60,120mg/kg, 1 day 2 times, administration 10 days, observe the impact of medicine on the toxicity of duck and duck serum DHB DNA, and compare with Acyclovir.Experiment shows: n of high dose oral group 120mg/kg, 1 day 2 times 10 days, non-toxic.Intraperitoneal injection 30mg/kg group, by pairing statistics, after administration, after the 10th day and drug withdrawal, 3 days treatment group duck serum DHBV-DNA have highly significant to decline and significantly decline (P<0.01-0.05); Compare with respective control group by statistics in groups, after administration after the 10th day and drug withdrawal 3 days, can highly significant and reduction DHBV infected duck serum DHBV-DNA level (P<0.01-0.05) significantly.Oral administration 60mg/kg, by pairing statistics, after drug withdrawal, 3 days treatment group duck serum DHBV-DNA have remarkable result (P<0.05); Add up in groups, after administration, after the 10th day and drug withdrawal, 3 days treatment group duck serum DHBV-DNA are decreased significantly (P<0.05).Within after oral 120mg/kg administration after the 5th day, the 10th day and drug withdrawal 3 days, by pairing statistics, treatment group duck serum DHBV-DNA has significantly and highly significant decline (P<0.05-0.01); Statistical treatment in groups, after administration, after the 5th day, the 10th day and drug withdrawal, 3 days treatment group duck serum DHBV-DNA have highly significant and significantly decline (P<0.01-0.05).Acyclovir contrast has remarkable result, and illustrative experiment is credible.Conclusion: extract intraperitoneal injection 30mg/kg; Oral administration 60-120mg/kg is effective to duck hepatitis B virus infection.
10. on the impact of rat blood serum MDA content and SOD activity
Get male 20 months aged Wistar rats 40, body weight 400 ~ 500g, is divided into four groups at random: control group (feed basal feed), the large, medium and small dosage group of extract (feed basal feed add extract 60,40,20mgkg
-1d
-1).Continuous nursing 4w, in experiment the 29th day, fasting 12h, Serum MDA (MDA) and superoxide dismutase (SOD) value were surveyed in femoral artery blood sampling.Use SPSS10.0 software analysis, compare between group with t inspection, the results are shown in Table 3.
Table 3. extract of the present invention is on the impact (x ± s, n=10) of rat blood serum MDA content and SOD activity
| Group | MDA(nmol/ml) | SOD(NU/ml) |
| Control group | 8.92±0.56 | 181.45±7.15 |
| Extract (greatly) | 3.44±0.40* | 194.58±8.55* |
| Extract (in) | 4.26±0.24* | 190.36±8.82* |
| Extract (little) | 4.63±0.48* | 187.76±9.04** |
Compare with control group: * p<0.01; * p<0.05.
Result shows, extract of the present invention can reduce old rats Content of MDA, raises old rats activity of SOD in serum, compares that there were significant differences with control group.
11. Antioxidative Activity Determinations
Adopt DPPH oxidizing process; to 1 of 3ml 25ug/mL; 150ul sample (replacement of blank equivalent methyl alcohol) is added in 1-hexichol-2-bitter taste acyl group (DPPH) solution; cumulative volume 3.15ml; mixing; after placing 30 minutes in 37 DEG C, survey its light absorption value with E-722 type visible spectrophotometer at 520nm place.Extract sample is 1mg/ml, 2mg/ml, 4mg/ml, 6mg/ml and 8mg/ml methanol solution, with BHT (BHT) for positive control.Sample is to clearance rate=[ODblank-ODsample/ODblank] × 100% of DPPH.In formula, the absorbance of ODblank:DPPH and solvent mixed liquor, the absorbance after ODsample:DPPH and example reaction.Result shows, and extract sample has extremely strong Scavenging activity to DPPH, its IC
50for 2.3mg/ml, than BHT (IC
504.2mg/ml) activity is stronger.
Four of the object of the invention is to provide Ilex kudincha C. J. Tseng extract and is preparing the application in medicine, health products, comprise separately or with the active ingredient combinations of other medicinal license, the carrier being equipped with suitable pharmaceutic adjuvant or pharmaceutically permitting, apply current known formulation process method, make various oral or parenteral dosage form, as tablet, hard shell capsules, dripping pill, oral liquid, granule, parenteral solution, freeze-dried powder etc.
Accompanying drawing explanation
Figure 13,4-, 3,5-and the CD collection of illustrative plates of 4,5-DCQA
The typical HPLC chromatogram of Fig. 2 extract of the present invention, chromatographic condition: chromatographic column VP-ODS, 150L × 4.6mm; Mobile phase MeOH-0.1%TFA gradient elution (time: 0min → 40min; MeOH:20% → 60%, 0.1%TFA:80% → 40%); Wavelength 328nm; Flow velocity 1ml/min.
The X-ray single crystal diffraction structural drawing of Fig. 3 Ilex Latifolia Thunb cyanogen glycosides
Preparation method's process flow diagram of Fig. 4 extract of the present invention
The HPLC of Fig. 5 extract of the present invention, crude extract and Ilex Latifolia Thunb cyanogen glycosides compares, chromatographic condition: chromatographic column VP-ODS, 150L × 4.6mm; Mobile phase MeOH-0.1%TFA gradient elution (time: 0min → 40min; MeOH:20% → 60%, 0.1%TFA:80% → 40%); Wavelength 259nm; Flow velocity 1ml/min.
Embodiment
With embodiment more specifically, method for preparing extractive of the present invention and the application in all kinds of preparation of preparation thereof are illustrated below, but content of the present invention is not limited to this.
Embodiment 1: the preparation of Ilex kudincha C. J. Tseng total phenolics
Get Ilex kudincha C. J. Tseng leaf 1kg, be ground into meal, add 95% reflow of alcohol and extract 3 times, merge extract, reduced pressure concentration, obtains alcohol medicinal extract 280g.Medicinal extract 1.5L purified water stirring and dissolving, drips dilute sodium hydroxide adjust pH about 7, centrifugal, filters, and filtrate to pH 2, leaves standstill 2 hours with 5% hcl acidifying, filters, and precipitation washes with water to efflux pH about 5, drains, must precipitate about 128g.Filtrate is added in polyamide (30 ~ 60 order) adsorption column, first washes with water, to efflux lighter and acidity is down to pH about 5 time, use 80% alcohol wash-out instead, collect alcohol eluent, reduced pressure concentration, obtain paste and be about 12g, be incorporated to sediment fraction.With sherwood oil backflow degreasing 3 times after precipitation drying, filter, volatilize, then extract 4 times with acetone reflux, merge extract, recycling design, obtains total phenolics 82g.Its 3,5-and 4,5-DCQA content sum be 39% (weight), substantially not containing Ilex Latifolia Thunb cyanogen glycosides, lightly seasoned not bitter, can be used as the raw material of various oral and external preparation.Embodiment 2: the preparation of Ilex kudincha C. J. Tseng total phenolics
Get Ilex kudincha C. J. Tseng leaf 1kg, be ground into meal, boiling 3 times, merge extract, reduced pressure concentration, obtains medicinal extract 220g.Medicinal extract 1.5L water stirring and dissolving, adds 5% sodium carbonate adjust pH about 7, centrifugal, filters, and filtrate to pH2, leaves standstill 2 hours with 5% sulfuric acid acidation, filters, and precipitation washes with water to efflux about pH5, drains, must precipitate about 100g.Filtrate is added in polyamide (30 ~ 60 order) adsorption column, first washes with water, to efflux lighter and acidity is down to about pH5 time, use 60% alcohol wash-out instead, collect alcohol eluent, reduced pressure concentration, obtain paste and be about 10g, be incorporated to sediment fraction.With hexane backflow degreasing 3 times after precipitation drying, filter, volatilize, then use ethyl acetate refluxing extraction 4 times, merge extract, recycling design, obtains total phenolics 85g.Its 3,5-and 4,5-DCQA content sum be about 42%, substantially not containing Ilex Latifolia Thunb cyanogen glycosides, lightly seasoned not bitter, can be used as the raw material of various oral and external preparation.
Embodiment 3: the preparation of Ilex kudincha C. J. Tseng total phenolics salt
Example 1 or 2 gained total phenolics 20g, slow gradation adds 5% Sodium hydroxide q. s, makes abundant dissolving under stirring, controls pH value of solution 7 ~ 8, and filter, spraying dry, obtains total phenolics salt 19g.This product good water solubility, can be used as the raw material of various solid and liquid preparation.
Embodiment 4: the preparation of injection Ilex kudincha C. J. Tseng total phenolics salt
Example 1 or 2 gained total phenolics 30g, adds 100ml 95% alcohol and makes dissolving, admix appropriate polyamide, dry, add in polyamide column, first wash with water, then wash with 5% alcohol, then wash with 80% alcohol, collect 80% alcohol eluent, reduced pressure concentration, obtain paste 18g; Continuation acetone reflux extracts 4 times, merges extract, recycling design, and appropriate 5% sodium carbonate of gained paste dissolves, and control pH value of solution 7 ~ 8, ultrafiltration, reduced pressure concentration, spraying dry, obtains brownish-yellow powder 14g.Its 3,5-and 4,5-DCQA content sum be about 80% (weight), not containing saponin(e and Ilex Latifolia Thunb cyanogen glycosides, good water solubility, can be used as injection raw material.
Embodiment 5: prepared by tablet
Get total phenolic acid extract 20g of the present invention, mix with starch 100g, dextrin 5g, add 10% starch slurry softwood, granulate with 14 order nylon screens, 60 ~ 70 DEG C of aeration-dryings, the whole grain of 16 mesh sieve, adds dolomol 1.5g, sodium carboxymethyl cellulose 5g, mixing, be pressed into 1000, dressing, to obtain final product, and every sheet is containing extract 20mg.Dosage and number of times are determined according to Clinical efficacy.
Embodiment 6: prepared by capsule
Get total phenolic acid extract 20g of the present invention, mix with starch 120g, dolomol 2g, be directly filled to 1000, polishing with Autocapsulefillingmachine, obtain final product, every containing extract 20mg.Dosage and number of times are determined according to Clinical efficacy.
Embodiment 7: prepared by dripping pill
Get total phenolic acid extract 12g of the present invention, drop in the Macrogol 6000 of 32g heating and melting, be stirred to dissolving, be transferred in reservoir, airtight and insulation at 80 ~ 90 DEG C, regulate pill dripping machine drop quantitative valve, instill in the liquid paraffin of 10 ~ 15 DEG C from top to bottom, make 1000 altogether, the dripping pill of formation is drained and wipes liquid paraffin, be drying to obtain, every containing extract 12mg.Dosage and number of times are determined according to Clinical efficacy.
Embodiment 8: prepared by oral liquid
Get total phenolics salt extract 20g of the present invention, mix with honey 400g, sucrose 100g, Sodium Benzoate 6g and distilled water 2000ml, be heated to 85 ~ 90 DEG C, be stirred to dissolve, insulation 30min, filter, filtrate is diluted with water to 10000ml, stirs evenly, embedding (often propping up 10ml), sterilizing, to obtain final product.
Embodiment 9: prepared by granule
Get total phenolic acid extract 4g of the present invention, dextrin 16g, cane sugar powder 230g and appropriate amount of ethanol, mixing, cross 10 mesh sieves and make particle, in 60 ~ 70 DEG C of dryings, whole grain, packing, to obtain final product, often the heavy 2.5g of bag.
Embodiment 10: prepared by parenteral solution
Get total phenolics salt 50g of the present invention, inject and make dissolving in right amount with water, 0.02% activated charcoal adding amount of preparation stirs 5 ~ 10 minutes, and filter, filtrate is diluted to about 10L, adding sodium chloride regulates osmotic pressure to isotonic, adjust pH 7.5 ~ 8.0, filter, embedding becomes 1000 (10ml/ props up), sterilizing, to obtain final product.Can injection for intravenous administration.Dosage and number of times are determined according to Clinical efficacy.
Embodiment 11: prepared by freeze-dried powder
Total phenolics salt 50g of the present invention is got under aseptic condition, be placed in sterile chamber, inject and be about 900ml with water, be stirred to dissolve, adjust ph to 7.0 ~ 7.5, inject water to 1000ml, then 0.02% activated charcoal adding amount of preparation stirs 5 ~ 10min, filters, ultrafiltration with aseptic suction funnel, filtrate is sub-packed in ampoule after the assay was approved, frozen drying, aseptic sealing by fusing and get final product, often props up 50mg, inject before use and make dissolving in right amount with water, with slowly drip-feed after sodium chloride transfusion 250 ~ 500ml dilution.Dosage and number of times are determined according to Clinical efficacy.
Embodiment 12: prepared by compound capsule
Get total phenolic acid extract 20g of the present invention, mix with notoginsenoside 20g, starch 150g and ethanol in proper amount, cross 10 mesh sieves, dry, whole grain, adds dolomol 2g, and mixing, is filled to 1000 with Autocapsulefillingmachine, polishing, obtains final product.Every containing extract and each 20mg of notoginsenoside.Can be for oral use in the control of various ischemic angiocardiopathy and cerebrovascular disease.Dosage and number of times are determined according to Clinical efficacy.
Claims (3)
1. there is the application using the Ilex Latifolia Thunb cyanogen glycosides of Formula Il structure as detection of drugs objectionable impurities index components,
2. application according to claim 1, is characterized in that, described medicine is Ilex kudincha C. J. Tseng extract and/or its preparation.
3. application according to claim 2, is characterized in that, as actual content≤0.2% of the Ilex Latifolia Thunb cyanogen glycosides in total phenolic acid extract (weight) of detection of drugs objectionable impurities index components.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410633217.6A CN104374890B (en) | 2011-06-16 | 2011-06-16 | A kind of Ilex kudincha C. J. Tseng extract |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410633217.6A CN104374890B (en) | 2011-06-16 | 2011-06-16 | A kind of Ilex kudincha C. J. Tseng extract |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110162622.0A Division CN102827001B (en) | 2011-06-16 | 2011-06-16 | A kind of Kudincha Holly extract |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104374890A true CN104374890A (en) | 2015-02-25 |
| CN104374890B CN104374890B (en) | 2016-07-13 |
Family
ID=52553935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410633217.6A Active CN104374890B (en) | 2011-06-16 | 2011-06-16 | A kind of Ilex kudincha C. J. Tseng extract |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104374890B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688955A (en) * | 2015-04-02 | 2015-06-10 | 朱明德 | Chinese herb extracts for treating coronary heart disease angina and preparation method and application thereof |
| CN113735920A (en) * | 2021-09-09 | 2021-12-03 | 广西中医药大学 | Application of cyanogenic glycoside compound Menisdaurin F in preparation of anti-hepatitis B virus pharmaceutical composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101775061A (en) * | 2009-09-15 | 2010-07-14 | 沈阳药科大学 | Ilex latifolia thunb saponin compound |
-
2011
- 2011-06-16 CN CN201410633217.6A patent/CN104374890B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101775061A (en) * | 2009-09-15 | 2010-07-14 | 沈阳药科大学 | Ilex latifolia thunb saponin compound |
Non-Patent Citations (4)
| Title |
|---|
| A.SOSA等: "STRUCTURE OF A CYANOGLUCOSIDE OF LITHOSPERMUM PURPUREO-CAERULEUM", 《PHYTOCHEMNTRY》 * |
| ADOLF NAHRSTEDT等: "STRUCTURAL REVISION OF A PUTATIVE CYANOGENIC GLUCOSIDE FROM ILEX AQUIFOLIUM", 《PHYTOCHEMISTRY》 * |
| DAVID S.SEIGLER等: "Cyanogenic glycosides and menisdaurin from Guazuma ulmifolia，Ostrya virginiana,Tiquilia plicata,and Tiquilia canescens", 《PHYTOCHEMISTRY》 * |
| 许实波等: "苦丁茶水提物的毒理学研究", 《中山大学学报(自然科学版)》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688955A (en) * | 2015-04-02 | 2015-06-10 | 朱明德 | Chinese herb extracts for treating coronary heart disease angina and preparation method and application thereof |
| CN113735920A (en) * | 2021-09-09 | 2021-12-03 | 广西中医药大学 | Application of cyanogenic glycoside compound Menisdaurin F in preparation of anti-hepatitis B virus pharmaceutical composition |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104374890B (en) | 2016-07-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102670673B (en) | The application of Flos abelmoschi manihot active component in the medicine of preparation control metabolic disease | |
| CN101297880B (en) | Active extract containing phlorizin and uses thereof | |
| CN101554409B (en) | Long pepper alkaloid and preparation method, preparation and application thereof | |
| CN102283870B (en) | High-purity folium ginkgo composition, preparation including same and preparation method thereof | |
| CN102827001B (en) | A kind of Kudincha Holly extract | |
| CN101119740B (en) | Use of radix sanguisorbae and its extract for preparing medicament to increase RBC and hemoglobin | |
| CN103169788B (en) | Chinese date leaf extractive and application thereof in preparation of medicament or health food for preventing and treating liver injury | |
| CN102697982B (en) | Composition having auxiliary blood fat reducing effect and preparation method thereof | |
| JP2010528063A (en) | Method and use for obtaining an extract containing sequoyitol from a plant belonging to the genus Rhododendron, soybean, genus Ginkgo | |
| CN1173707C (en) | Medicinal composition containing baicalin and caffoeoylchinic acid | |
| WO2019218538A1 (en) | Composition for reducing weight and lowering glucose and lipids, preparation method therefor and use thereof | |
| CN104374890B (en) | A kind of Ilex kudincha C. J. Tseng extract | |
| CN1329049C (en) | Blood sugar- and blood pressure-lowering medicine | |
| CN102153614A (en) | Method for preparing effective monomer of total alkaloid extract of holarrhena antidysenterica and application thereof | |
| CN1788758A (en) | Use of traditional Chinese medicine garden burnet and its extract in preparing drug for raising red cell and blood hemoglobin | |
| CN102838485B (en) | A kind of Cortex Ilicis Rotundae extract | |
| CN101612184B (en) | Multiradiate fleabane extract, composition containing same, preparation method and application thereof | |
| CN102048874B (en) | General flavone extractive of immature bitter orange or bitter orange extracted through water decoction and use of general flavone extractive | |
| CN100444849C (en) | New use of tribulus terrestris extraction | |
| CN103110680A (en) | Preparation method of total phenolic acid of erigeron breviscapus | |
| CN107334813A (en) | A kind of cubic parthenium extract and its preparation method and purposes | |
| CN103800389B (en) | Hypoglycemic activity composition and preparation method thereof and application in a kind of Sarcodon leucopus | |
| CN1887309B (en) | Extraction of effective red sage components for preventing and treating osteoporosis and depression | |
| CN1150839C (en) | Health food with blood pressure and blood lipoid regulating function and its production process | |
| CN104258034A (en) | Traditional Chinese medicine composition for boosting immunity |
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 | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221123 Address after: 310030 Station 23, Room 201, Building 2, No. 176, Zixia Street, Xihu District, Hangzhou, Zhejiang Patentee after: Hangzhou Taozhugong Biotechnology Co.,Ltd. Address before: No. 8, Zone 2, West Lake Industrial Park, Tangxia Town, Dongguan, Guangdong 523711 Patentee before: DONGGUAN LING'AO BIOTECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20240513 Address after: Room 102, No. 10 Hongye North Road, Tangxia Town, Dongguan City, Guangdong Province, 523000 Patentee after: DONGGUAN LING'AO BIOTECHNOLOGY Co.,Ltd. Country or region after: China Address before: 310030 Station 23, Room 201, Building 2, No. 176, Zixia Street, Xihu District, Hangzhou, Zhejiang Patentee before: Hangzhou Taozhugong Biotechnology Co.,Ltd. Country or region before: China |