CN102824417A - New method for treating helicobacter pylori related diseases - Google Patents
New method for treating helicobacter pylori related diseases Download PDFInfo
- Publication number
- CN102824417A CN102824417A CN2012103528566A CN201210352856A CN102824417A CN 102824417 A CN102824417 A CN 102824417A CN 2012103528566 A CN2012103528566 A CN 2012103528566A CN 201210352856 A CN201210352856 A CN 201210352856A CN 102824417 A CN102824417 A CN 102824417A
- Authority
- CN
- China
- Prior art keywords
- extract
- herba polygoni
- polygoni capitati
- ethanol
- water
- 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 57
- 238000000034 method Methods 0.000 title claims abstract description 47
- 201000010099 disease Diseases 0.000 title claims abstract description 40
- 229940037467 helicobacter pylori Drugs 0.000 title abstract description 46
- 241000590002 Helicobacter pylori Species 0.000 title abstract description 44
- 239000000284 extract Substances 0.000 claims abstract description 161
- 239000003814 drug Substances 0.000 claims abstract description 50
- 206010019375 Helicobacter infections Diseases 0.000 claims abstract description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 188
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 58
- 238000002360 preparation method Methods 0.000 claims description 46
- 210000001156 gastric mucosa Anatomy 0.000 claims description 33
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 32
- 208000007882 Gastritis Diseases 0.000 claims description 30
- 229960003022 amoxicillin Drugs 0.000 claims description 27
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 26
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 26
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 26
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical group O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 25
- 229960002626 clarithromycin Drugs 0.000 claims description 25
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 23
- 229960000282 metronidazole Drugs 0.000 claims description 23
- 238000010992 reflux Methods 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 239000000463 material Substances 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 21
- 238000001035 drying Methods 0.000 claims description 18
- 238000000194 supercritical-fluid extraction Methods 0.000 claims description 18
- -1 nitre imidazoles Chemical class 0.000 claims description 17
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 16
- 241000205407 Polygonum Species 0.000 claims description 16
- 239000001569 carbon dioxide Substances 0.000 claims description 16
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 16
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 16
- 239000000047 product Substances 0.000 claims description 14
- 208000023652 chronic gastritis Diseases 0.000 claims description 13
- 229940126409 proton pump inhibitor Drugs 0.000 claims description 10
- 239000003643 water by type Substances 0.000 claims description 10
- 206010003694 Atrophy Diseases 0.000 claims description 9
- 206010054949 Metaplasia Diseases 0.000 claims description 9
- 230000037444 atrophy Effects 0.000 claims description 9
- 230000006837 decompression Effects 0.000 claims description 9
- 230000000968 intestinal effect Effects 0.000 claims description 9
- 230000015689 metaplastic ossification Effects 0.000 claims description 9
- 239000000612 proton pump inhibitor Substances 0.000 claims description 9
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims description 8
- 239000004599 antimicrobial Substances 0.000 claims description 8
- 229960000381 omeprazole Drugs 0.000 claims description 8
- 206010025323 Lymphomas Diseases 0.000 claims description 7
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 7
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 206010017758 gastric cancer Diseases 0.000 claims description 7
- 201000005917 gastric ulcer Diseases 0.000 claims description 7
- 201000011549 stomach cancer Diseases 0.000 claims description 7
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 6
- 208000004300 Atrophic Gastritis Diseases 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 208000036495 Gastritis atrophic Diseases 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 claims description 6
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 claims description 6
- 206010043561 Thrombocytopenic purpura Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 208000007502 anemia Diseases 0.000 claims description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 6
- 206010008118 cerebral infarction Diseases 0.000 claims description 6
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 6
- 208000016644 chronic atrophic gastritis Diseases 0.000 claims description 6
- 208000029078 coronary artery disease Diseases 0.000 claims description 6
- 208000000718 duodenal ulcer Diseases 0.000 claims description 6
- 235000013305 food Nutrition 0.000 claims description 6
- 229960003174 lansoprazole Drugs 0.000 claims description 6
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 claims description 6
- 229960005019 pantoprazole Drugs 0.000 claims description 6
- 230000000306 recurrent effect Effects 0.000 claims description 6
- 229910021647 smectite Inorganic materials 0.000 claims description 6
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 claims description 6
- 229960004291 sucralfate Drugs 0.000 claims description 6
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 241000764065 Persicaria capitata Species 0.000 abstract description 4
- 208000024891 symptom Diseases 0.000 abstract description 4
- 229960004756 ethanol Drugs 0.000 description 54
- 241000894006 Bacteria Species 0.000 description 43
- 230000001580 bacterial effect Effects 0.000 description 39
- 238000012360 testing method Methods 0.000 description 33
- 238000002474 experimental method Methods 0.000 description 32
- 230000000844 anti-bacterial effect Effects 0.000 description 31
- 239000007788 liquid Substances 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- 239000000203 mixture Substances 0.000 description 21
- 239000000843 powder Substances 0.000 description 21
- 239000000523 sample Substances 0.000 description 21
- 229940079593 drug Drugs 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- 210000002784 stomach Anatomy 0.000 description 18
- 206010059866 Drug resistance Diseases 0.000 description 17
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical group OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 16
- 230000003115 biocidal effect Effects 0.000 description 15
- 238000000926 separation method Methods 0.000 description 14
- 230000002496 gastric effect Effects 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 238000004043 dyeing Methods 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 108010046334 Urease Proteins 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 238000010790 dilution Methods 0.000 description 11
- 239000012895 dilution Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000006161 blood agar Substances 0.000 description 10
- 230000001408 fungistatic effect Effects 0.000 description 10
- 239000013642 negative control Substances 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 210000004400 mucous membrane Anatomy 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 229920001817 Agar Polymers 0.000 description 8
- 102000004316 Oxidoreductases Human genes 0.000 description 8
- 108090000854 Oxidoreductases Proteins 0.000 description 8
- 239000008272 agar Substances 0.000 description 8
- 238000002481 ethanol extraction Methods 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 235000004515 gallic acid Nutrition 0.000 description 8
- 229940074391 gallic acid Drugs 0.000 description 8
- 210000004877 mucosa Anatomy 0.000 description 8
- 210000004203 pyloric antrum Anatomy 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 102000016938 Catalase Human genes 0.000 description 7
- 108010053835 Catalase Proteins 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 229930003944 flavone Natural products 0.000 description 7
- 150000002213 flavones Chemical class 0.000 description 7
- 235000011949 flavones Nutrition 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 238000001802 infusion Methods 0.000 description 7
- 230000008520 organization Effects 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000003463 adsorbent Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- HNBDQABBWNOTRU-UHFFFAOYSA-N thalline Chemical compound C1=CC=[Tl]C=C1 HNBDQABBWNOTRU-UHFFFAOYSA-N 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 241001674329 Helicobacter pylori 26695 Species 0.000 description 5
- 241000283898 Ovis Species 0.000 description 5
- 102000011759 adducin Human genes 0.000 description 5
- 108010076723 adducin Proteins 0.000 description 5
- 238000004500 asepsis Methods 0.000 description 5
- 230000003385 bacteriostatic effect Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000013372 meat Nutrition 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 238000004062 sedimentation Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 235000014347 soups Nutrition 0.000 description 5
- 208000005156 Dehydration Diseases 0.000 description 4
- 208000004880 Polyuria Diseases 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000035619 diuresis Effects 0.000 description 4
- 230000008029 eradication Effects 0.000 description 4
- 239000000469 ethanolic extract Substances 0.000 description 4
- 210000004907 gland Anatomy 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000036285 pathological change Effects 0.000 description 4
- 231100000915 pathological change Toxicity 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 238000001694 spray drying Methods 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 241000219050 Polygonaceae Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 235000012791 bagels Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 208000001848 dysentery Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000003448 neutrophilic effect Effects 0.000 description 3
- 235000010603 pastilles Nutrition 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 210000000582 semen Anatomy 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 206010062049 Lymphocytic infiltration Diseases 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 206010037596 Pyelonephritis Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229910000831 Steel Inorganic materials 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
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 201000003146 cystitis Diseases 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000000446 fuel Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 239000006101 laboratory sample Substances 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 230000001047 pyretic effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 238000003805 vibration mixing Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 241000094396 Bolitoglossa carri Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000186427 Cutibacterium acnes Species 0.000 description 1
- 241001464975 Cutibacterium granulosum Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 206010013183 Dislocation of vertebra Diseases 0.000 description 1
- 208000036649 Dysbacteriosis Diseases 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000012895 Gastric disease Diseases 0.000 description 1
- 206010061164 Gastric mucosal lesion Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000025174 PANDAS Diseases 0.000 description 1
- 208000021155 Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Diseases 0.000 description 1
- 240000000220 Panda oleosa Species 0.000 description 1
- 235000016496 Panda oleosa Nutrition 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000191992 Peptostreptococcus Species 0.000 description 1
- 108010093965 Polymyxin B Proteins 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000594182 Sarcophaga sigma Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 244000061458 Solanum melongena Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000191963 Staphylococcus epidermidis Species 0.000 description 1
- 206010042566 Superinfection Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000002814 agar dilution Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000000222 eosinocyte Anatomy 0.000 description 1
- 239000002389 essential drug Substances 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 210000003495 flagella Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000002575 gastroscopy Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229920000024 polymyxin B Polymers 0.000 description 1
- 229960005266 polymyxin b Drugs 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940055019 propionibacterium acne Drugs 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 201000007094 prostatitis Diseases 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 238000009589 serological test Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 208000018556 stomach disease Diseases 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 208000016752 upper digestive tract disease Diseases 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a new method for treating helicobacter pylori related diseases, in particular to application of polygonum capitatum or extract thereof in preparing a medicine for treating and/or preventing the diseases or symptoms related to helicobacter pylori infection. The invention discovers that the extract can effectively suppress the helicobacter pylori.
Description
Technical field
The present invention relates to the field of Chinese medicines; Particularly; The present invention relates to treat the new method of helicobacter pylori relevant disease; Be specifically related to a kind of polygonaceae plant and extract thereof and be used to treat the new method of helicobacter pylori relevant disease, particularly Chinese herbal medicine Herba Polygoni Capitati or its extract are used to treat the new method of helicobacter pylori relevant disease.
Background technology
Herba Polygoni Capitati (Polygonum capitatum Buch.-Ham.ex D.Don) is a kind of Polygonaceae arsesmart, is perennial herb, another name Herba Polygoni Capitati, Herba Polygoni Capitati, Polygonum capitatum Buch, water silk ball, Flos Carthami Herba Violae, completely red etc.In areas such as Chinese Guizhou, Yunnan, Guangxi, Sichuan, Tibet, Hubei, Hunan and Jiangxi distribution is arranged all, mainly be grown in hillside, mountain valley and be rich in the husky shale area in coal seam.Herb has the effect of heat-clearing and toxic substances removing, dissipating blood stasis, inducing diuresis for treating stranguria syndrome.According to " Guangxi Chinese medicinal herbal " second record in 1963, Herba Polygoni Capitati was mainly used in treatment rheumatalgia; " Chinese medicine voluminous dictionary " first volume record in 1977, Herba Polygoni Capitati is mainly used in treatment dysentery, nephritis, cystitis and lithangiuria etc.Among the people generally with Herba Polygoni Capitati with being decocted in water for oral dose, therapeutic effect is apparent in view, but takes inconvenience.One Chinese patent application prospectus CN1054899A discloses a kind of miganling instant herbal medicine, syrup production technology in (one Chinese patent application numbers 90107810.7, open day on October 2nd, 1991).This production technology is to be that the raw material water decocted 30-60 minute with four seasons grass, and extracting liquid filtering concentrates; Its supernatant concentrating under reduced pressure is become cream; Reuse 60-70% ethanol extraction with the ethanol extract vacuum drying, gets Herba Polygoni Capitati extractum; Further be mixed with electuary or syrup, it is believed that this has detoxifcation, dissipating blood stasis, diuresis, treating stranguria effect.
Recorded the Chinese patent medicine preparation of " the clear granule of pyretic stranguria " by name in the Ministry of Health of the People's Republic of China " drug standard-Chinese traditional patent formulation preparation " (the 17) that Ministry of Health of the People's Republic of China's committee of pharmacopeia was compiled in 1998, it is processed through twice after-filtration of Herba Polygoni Capitati decocte with water concentrated.
CN 1481832A (one Chinese patent application number 02129686.3; Open day on March 17th, 2004) and CN 1483466A (one Chinese patent application number 03146381.9; Open day on March 24th, 2004) Herba Polygoni Capitati extract is disclosed; It is prepared by following steps basically: a. is decocted at twice by the aquatic foods article of Herba Polygoni Capitati herb or dry product water or divides reflux, extract, two to three times with alcohol-water mixture, each 1-2 hour, merges decoction liquor; Relative density during filtering and concentrating to 20 ° C is 1.2, and spray drying or drying under reduced pressure obtain; Perhaps, b. carries medicinal residues by Herba Polygoni Capitati herb and water thereof and obtains through carbon dioxide supercritical fluid extraction.It is believed that this extract can be used for antibiotic, antiinflammatory, analgesia, diuresis, treatment urinary system calculus, treatment pyelonephritis and prostatitis.
Helicobacter pylori (Helicobacter pylori can abbreviate Hp or HP as in this article) is a kind of microaerophilic gram negative bacteria that is prevalent in people's gastric mucosa.Helicobacter pylori is the antibacterial of a kind of one pole, many flagellums, terminal blunt circle, helically bent; Long 2.5～4.0 μ m; Wide 0.5～1.0 μ m often is typical helical form or arc on the gastric epithelial cell surface, when on solid medium, growing; Except that typical form, sometimes shaft-like or spherical shape can appear.Helicobacter pylori nature crowd's in the whole world infection rate surpasses 50%, and the population that does not almost have a kind of chronic infectious disease can make the whole world surpass half is in the world infected, and developing country is higher than developed country.China belongs to developing country, and the Helicobacter pylori infection rate is high.Digest the Helicobacter pylori infection Epidemiological study demonstration that relates to the natural crowd at 20 provinces and cities in the whole nation, 40 centers that disease branch helicobacter pylori group is done by Chinese Medical Association: China's Helicobacter pylori infection rate is 40-90%, average out to 59%; Existing disease infection rate is 42-64%, average 55%.It is believed that Hp infects and the main paathogenic factor of multiple prevalent upper gastrointestinal tract disease such as peptic ulcer, gastritis, gastric mucosa dependency lymphoma (MALT) and gastric cancer etc.Known for example following disease or disease infect relevant with Hp directly or indirectly: gastric mucosa dependency lymphoma, peptic ulcer, gastric ulcer, duodenal ulcer, acute or chronic gastritis, superficial gastritis, atrophic gastritis, gastric cancer, cardiovascular disease, coronary heart disease, arteriosclerosis, cerebral infarction, hypertension, anemia, iron deficiency anemia, recurrent peptic ulcer, gastric mucosa atrophy, intestinal epithelial metaplasia and thrombocytopenic purpura (Baidu's encyclopaedia: http://baike.baidu.com/view/36784.htm; 2011-09-15); Can also comprise the complication of following these diseases or disease, suppress relapse rate that helicobacter pylori helps reducing peptic ulcer, block or delay further developing of gastric mucosa atrophy and intestinal epithelial metaplasia.World Health Organization (WHO)/international cancer research institution (WHO/IARC) was decided to be I class carcinogen with helicobacter pylori in 1994.Hp anti-infective therapy mainly is to be three or the quadruple chemotherapy on basis with the antibiotic, but unites and be widely used in anti-Hp treatment along with multiple antibiotic, and Hp is serious day by day to antibiotic drug resistance problem, has become the main cause of eradication therapy failure.
This area expectation is useful on the new treatment of helicobacter pylori relevant disease.
Summary of the invention
The objective of the invention is to for a kind of method that treats and/or prevents with Helicobacter pylori infection diseases associated or disease is provided clinically.The inventor is surprisingly found out that Herba Polygoni Capitati or its extract are suppressing helicobacter pylori and treating and/or preventing the effect that has desirable with Helicobacter pylori infection diseases associated or disease.The present invention is based on this and be accomplished.
For this reason, first aspect present invention provides Herba Polygoni Capitati or its extract to be used for treating and/or preventing the purposes with the medicine of Helicobacter pylori infection diseases associated or disease in preparation.
According to the purposes of first aspect present invention, wherein said Herba Polygoni Capitati is the aquatic foods article or the dry product of Herba Polygoni Capitati.
According to the purposes of first aspect present invention, wherein said Herba Polygoni Capitati is herb, aerial parts, leaf, flower, stem, seed or its combination that is selected from Herba Polygoni Capitati.
According to the purposes of first aspect present invention, wherein said Herba Polygoni Capitati is the aerial parts that is selected from Herba Polygoni Capitati.
According to the purposes of first aspect present invention, wherein said Herba Polygoni Capitati is leaf, flower, stem, seed or its combination that is selected from Herba Polygoni Capitati.
According to the purposes of first aspect present invention, wherein said extract is that Herba Polygoni Capitati water, ethanol, ethanol water or its combination are as solvent, through extracting the extract that obtains; Or Herba Polygoni Capitati is through the extract of carbon dioxide supercritical fluid extraction method acquisition.
According to the purposes of first aspect present invention, wherein said extract is the extract of the ethanol water of Herba Polygoni Capitati.In one embodiment, said ethanol water is 30 ~ 99% ethanol waters.In one embodiment, said ethanol water is 50 ~ 98% ethanol waters.In one embodiment, said ethanol water is 60 ~ 98% ethanol waters.In one embodiment, said ethanol water is 70 ~ 95% ethanol waters.
According to the purposes of first aspect present invention, wherein said extract is the extract according to the method preparation that comprises the steps: decocted and/or reflux, extract, concentrated extracting solution, drying by medicinal material of polygonum capilalum water, ethanol or ethanol water.
According to the purposes of first aspect present invention, wherein said extract obtains with the carbon dioxide supercritical fluid extraction Herba Polygoni Capitati.In one embodiment; Wherein said extract is the extract according to the preparation of the method that comprises the steps: use the carbon dioxide supercritical fluid extraction medicinal material of polygonum capilalum, and/or the medicinal residues that obtain through water, ethanol or ethanol water decoction and/or reflux, extract, with the carbon dioxide supercritical fluid extraction medicinal material of polygonum capilalum.
According to the purposes of first aspect present invention, wherein said extract is the extract according to the method preparation that comprises the steps: get medicinal material of polygonum capilalum, add 5 ~ 20 times (for example 5 ~ 15 times; For example 8 ~ 12 times) water, ethanol or ethanol water decoct and/or reflux, extract, 1 ~ 5 time (for example 2 ~ 3 times); Each 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour), collecting decoction; Filter; Filtrate decompression is concentrated into the thick paste that relative density is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4), and drying promptly gets.
Purposes according to first aspect present invention; Wherein said extract is the extract according to the method preparation that comprises the steps: get medicinal material of polygonum capilalum; Add 5 ~ 20 times (for example 5 ~ 15 times; For example 8 ~ 12 times) water, about 80 ~ 100 ° of C, decoct to extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is condensed into paste; Doubly measure 50 ~ 90% alcohol reflux 2-3 time with 2-5, ethanol extract is removed ethanol in 70-90 ° of C, vacuum drying promptly gets.
Purposes according to first aspect present invention; Wherein said and Helicobacter pylori infection diseases associated or disease include but not limited to; Gastric mucosa dependency lymphoma, peptic ulcer, gastric ulcer, duodenal ulcer, acute or chronic gastritis, superficial gastritis, atrophic gastritis, gastric cancer, cardiovascular disease, coronary heart disease, arteriosclerosis, cerebral infarction, hypertension, anemia, iron deficiency anemia, recurrent peptic ulcer, gastric mucosa atrophy, intestinal epithelial metaplasia and thrombocytopenic purpura, and their complication.
Known and Helicobacter pylori infection diseases associated or disease can adopt the drug combination therapeutic scheme; For example three or the tetrad therapeutic scheme; For example; The combined treatment of amoxicillin+clarithromycin+metronidazole; The perhaps combined treatment of proton pump inhibitor (omeprazole, lansoprazole and/or pantoprazole)+amoxicillin+clarithromycin, perhaps the combined treatment of omeprazole+clarithromycin+amoxicillin+ranitidine perhaps is aided with the combined treatment of gastric mucosa protectant such as but not limited to sucralfate, dioctahedral smectite etc. on their basis.And the present invention finds that Herba Polygoni Capitati extract has good bacteriostatic activity; Find surprisingly that particularly Herba Polygoni Capitati extract also is effective to the pathogen of some anti-amoxicillin, clarithromycin and/or metronidazole; Therefore can expect that Herba Polygoni Capitati extract of the present invention can use with these antiviral drug regimens or substitute them and use.Therefore, according to the purposes of first aspect present invention, also comprise one or more other medicine in the wherein said medicine, this other medicine is selected from: antimicrobial drug, proton pump inhibitor, gastric mucosa protectant etc.Described antimicrobial drug such as but not limited to: PCs is the amoxicillin for example, and Macrolide is clarithromycin for example, and the nitre imidazoles is metronidazole for example.Described proton pump inhibitor is such as but not limited to omeprazole, lansoprazole, pantoprazole.Described gastric mucosa protectant is such as but not limited to sucralfate, dioctahedral smectite etc.How those skilled in the art know according to existing knowledge Herba Polygoni Capitati according to the invention or its extract and said other medicine are made up.
Second aspect present invention provides the pharmaceutical composition that is used to treat and/or prevent with Helicobacter pylori infection diseases associated or disease, wherein comprises Herba Polygoni Capitati or its extract, and optional pharmaceutically acceptable carrier or excipient.
According to the pharmaceutical composition of second aspect present invention, wherein said Herba Polygoni Capitati is the aquatic foods article or the dry product of Herba Polygoni Capitati.
According to the pharmaceutical composition of second aspect present invention, wherein said Herba Polygoni Capitati is herb, aerial parts, leaf, flower, stem, seed or its combination that is selected from Herba Polygoni Capitati.
According to the pharmaceutical composition of second aspect present invention, wherein said Herba Polygoni Capitati is the aerial parts that is selected from Herba Polygoni Capitati.
According to the pharmaceutical composition of second aspect present invention, wherein said Herba Polygoni Capitati is leaf, flower, stem, seed or its combination that is selected from Herba Polygoni Capitati.
According to the pharmaceutical composition of second aspect present invention, wherein said extract is that Herba Polygoni Capitati water, ethanol, ethanol water or its combination are as solvent, through extracting the extract that obtains; Or Herba Polygoni Capitati is through the extract of carbon dioxide supercritical fluid extraction method acquisition.
According to the pharmaceutical composition of second aspect present invention, wherein said extract is the extract of the ethanol water of Herba Polygoni Capitati.In one embodiment, said ethanol water is 30 ~ 99% ethanol waters.In one embodiment, said ethanol water is 50 ~ 98% ethanol waters.In one embodiment, said ethanol water is 60 ~ 98% ethanol waters.In one embodiment, said ethanol water is 70 ~ 95% ethanol waters.
According to the pharmaceutical composition of second aspect present invention, wherein said extract is the extract according to the method preparation that comprises the steps: decocted and/or reflux, extract, concentrated extracting solution, drying by medicinal material of polygonum capilalum water, ethanol or ethanol water.
According to the pharmaceutical composition of second aspect present invention, wherein said extract obtains with the carbon dioxide supercritical fluid extraction Herba Polygoni Capitati.In one embodiment; Wherein said extract is the extract according to the preparation of the method that comprises the steps: use the carbon dioxide supercritical fluid extraction medicinal material of polygonum capilalum, and/or the medicinal residues that obtain through water, ethanol or ethanol water decoction and/or reflux, extract, with the carbon dioxide supercritical fluid extraction medicinal material of polygonum capilalum.
According to the pharmaceutical composition of second aspect present invention, wherein said extract is the extract according to the method preparation that comprises the steps: get medicinal material of polygonum capilalum, add 5 ~ 20 times (for example 5 ~ 15 times; For example 8 ~ 12 times) water, ethanol or ethanol water decoct and/or reflux, extract, 1 ~ 5 time (for example 2 ~ 3 times); Each 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour), collecting decoction; Filter; Filtrate decompression is concentrated into the thick paste that relative density is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4), and drying promptly gets.
Pharmaceutical composition according to second aspect present invention; Wherein said extract is the extract according to the method preparation that comprises the steps: get medicinal material of polygonum capilalum; Add 5 ~ 20 times (for example 5 ~ 15 times; For example 8 ~ 12 times) water, about 80 ~ 100 ° of C, decoct to extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is condensed into paste; Doubly measure 50 ~ 90% alcohol reflux 2-3 time with 2-5, ethanol extract is removed ethanol in 70-90 ° of C, vacuum drying promptly gets.
Pharmaceutical composition according to second aspect present invention; Wherein said and Helicobacter pylori infection diseases associated or disease include but not limited to; Gastric mucosa dependency lymphoma, peptic ulcer, gastric ulcer, duodenal ulcer, acute or chronic gastritis, superficial gastritis, atrophic gastritis, gastric cancer, cardiovascular disease, coronary heart disease, arteriosclerosis, cerebral infarction, hypertension, anemia, iron deficiency anemia, recurrent peptic ulcer, gastric mucosa atrophy, intestinal epithelial metaplasia and thrombocytopenic purpura, and their complication.
According to the pharmaceutical composition of second aspect present invention, wherein also comprise one or more and be selected from following medicine: antimicrobial drug, proton pump inhibitor, gastric mucosa protectant etc.Described antimicrobial drug such as but not limited to: PCs is the amoxicillin for example, and Macrolide is clarithromycin for example, and the nitre imidazoles is metronidazole for example.Described proton pump inhibitor is such as but not limited to omeprazole, lansoprazole, pantoprazole.Described gastric mucosa protectant is such as but not limited to sucralfate, dioctahedral smectite etc.
According to the pharmaceutical composition of second aspect present invention, it is the dosage form of oral or drug administration by injection.In one embodiment, said pharmaceutical composition is the form of tablet, capsule, granule, pill, oral solutions, injection (liquid drugs injection and/or powder pin) etc.
Third aspect present invention provides the method that treats and/or prevents with Helicobacter pylori infection diseases associated or disease, and this method comprises to the Herba Polygoni Capitati of the administration effective dose that needs are arranged or its extract.
Method according to third aspect present invention; Wherein said and Helicobacter pylori infection diseases associated or disease include but not limited to; Gastric mucosa dependency lymphoma, peptic ulcer, gastric ulcer, duodenal ulcer, acute or chronic gastritis, superficial gastritis, atrophic gastritis, gastric cancer, cardiovascular disease, coronary heart disease, arteriosclerosis, cerebral infarction, hypertension, anemia, iron deficiency anemia, recurrent peptic ulcer, gastric mucosa atrophy, intestinal epithelial metaplasia and thrombocytopenic purpura, and their complication.
According to the method for third aspect present invention, wherein also before using said Herba Polygoni Capitati or its extract, simultaneously or use one or more afterwards and be selected from following medicine: antimicrobial drug, proton pump inhibitor, gastric mucosa protectant etc.Described antimicrobial drug such as but not limited to: PCs is the amoxicillin for example, and Macrolide is clarithromycin for example, and the nitre imidazoles is metronidazole for example.Described proton pump inhibitor is such as but not limited to omeprazole, lansoprazole, pantoprazole.Described gastric mucosa protectant is such as but not limited to sucralfate, dioctahedral smectite etc.
Method according to third aspect present invention; Wherein said mammal is that any position at health is (particularly in the digestive tract; More particularly in the harmonization of the stomach duodenum) infect helicobacter pylori or have by the tendency of Helicobacter pylori infection or possible any mammal; Comprise the mankind, and performing animal (such as but not limited to: pig, cattle, sheep, horse etc.), experimental animal (such as but not limited to: Canis familiaris L., cat, rat, mice, rabbit, monkey etc.); Companion animals (such as but not limited to: pet dog, pet cat etc.), wild animal (such as but not limited to: tiger, ape, monkey, panda etc.); Animal for display (the for example mammal of zoo raising).
Arbitrary technical characterictic that arbitrary embodiment had of the arbitrary aspect of the present invention or this arbitrary aspect is suitable for arbitrary embodiment of other arbitrary embodiment or other arbitrary aspect equally; As long as they can be not conflicting; Certainly at where applicable each other, necessary words can be done suitably to modify to individual features.Do further to describe with characteristics to various aspects of the present invention below.
All documents that the present invention quoted from, their full content is incorporated this paper by reference into, and if the expressed implication of these documents and the present invention when inconsistent, be as the criterion with statement of the present invention.In addition; Various terms and phrase that the present invention uses have the general sense of well known to a person skilled in the art; Nonetheless; The present invention still hopes at this more detailed explanation and explanation to be done in these terms and phrase, and term of mentioning and phrase are as the criterion with the implication that the present invention was explained if any inconsistent with known implication.
In the present invention; Only if the linguistic context of being addressed clearly contains other implication; Otherwise the Herba Polygoni Capitati of mentioning is meant Polygonaceae arsesmart Herba Polygoni Capitati (Polygonum capitatum Buch.-Ham.ex D.D on); Comprise its bright article or dry product, comprise its herb, aerial parts, leaf, flower, stem, seed or its combination.
In the present invention, any disease can be represented in phrase " with Helicobacter pylori infection diseases associated or disease ", and its origin cause of formation is directly or indirectly relevant with Helicobacter pylori infection.In addition; Especially; " with Helicobacter pylori infection diseases associated or disease " in most cases directly translates into gastropathy, for example gastritis, gastric ulcer etc., therefore; The present invention uses the disease of Chinese medicine involved in the present invention or its extract for treating or prevention, comprises any origin cause of formation direct or indirect and Helicobacter pylori infection diseases associated or disease; And; As long as tried the individual's body endogenous cause of ill origin cause of formation directly or indirectly and Helicobacter pylori infection and the body illness or the disease that cause; Use Chinese medicine involved in the present invention or its extract for treating or prevention can demonstrate clinical effectiveness, then all fall into protection scope of the present invention.For example certain style such as patient; That health occurs is any (certain/some) the stomach discomfort symptom; And helicobacter pylori is arranged through detecting to infect in its stomach; Then use Chinese medicine involved in the present invention or its extract for treating or prevention can demonstrate clinical effectiveness, and this treatment or prevent related therapeutic use and pharmaceutical composition and Therapeutic Method, all fall into protection scope of the present invention.
In the present invention, term " extraction " can be the dipping under the room temperature, or extraction at elevated temperatures (for example decoct and/or reflux), the perhaps combination of these modes of operation.Can further include extract is further handled, for example further carry out purification, for example desolventize, precipitate the removal of impurity, solvent extraction, resin absorption separation etc.
As described herein, term " extract " will comprise the extract of any purity that can be used for realizing the object of the invention, and spirit is appreciated that the dna purity of extract of the present invention can change in the larger context to those skilled in the art according to the present invention.Herba Polygoni Capitati for example of the present invention extracts the extract that obtains; Difference according to different technological conditions; The 1kg Herba Polygoni Capitati is through extracting the extract that can obtain arbitrary amount between the 10g to 500g (for example 10g to 200g, for example 10g to 150g, for example 10g to 100g) that is different purity; Those skilled in the art can use the extract of different purity to allocate the compositions that is fit to needs according to different needs.In some embodiments of the present invention, described extract can be called extract powder.
In the present invention, can use the present composition of effective dose to be applied to have need receive examination individual.As described herein, term " effective dose " is meant the purpose dosage that can in the experimenter, realize preventing and/or treating situation according to the invention, obstacle, disease or disease.Those skilled in the art are context according to the present invention, can easily confirm the using dosage of the present composition.Especially, this is according to the present invention, and term " effective dose " is appreciated that to the present composition with reasonable effect/risk of being applicable to any therapeutic treatment and/or prevention than the q.s that treats and/or prevents said situation, obstacle, disease or disease.But the total consumption per day that it should be understood that the present composition can maked decision in the medical judgment scope by those skilled in the art reliably.For any concrete experimenter, the horizontal fibrous root of concrete prevention effective dose is decided according to multiple factor, and said factor comprises experimenter's age, body weight, general health situation, sex and diet; The concrete compositions that is adopted; Make up other therapeutic active substance of using or using simultaneously with the present composition; And the known similar factor of medical field.
The present invention provides and comprises and one or more nontoxic physiology's acceptable carriers compositions formulated together.Said compositions can be mixed with especially specially and supply Orally administered or the confession rectal administration with solid or liquid form, perhaps is mixed with to supply injection to use.
Supply Orally administered solid dosage forms to include but not limited to capsule, tablet, pill, powder and granule.In this type of solid dosage forms, reactive compound can be accepted excipient or carrier such as sodium citrate or dicalcium phosphate and/or following material with at least a inert physiology and mix: a) filler or extender such as starch, lactose, sucrose, glucose, mannitol and silicic acid; B) binding agent such as carboxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and Radix Acaciae senegalis; C) wetting agent such as glycerol; D) disintegrating agent such as agar, calcium carbonate, Rhizoma Solani tuber osi or tapioca, alginic acid, some silicate and sodium carbonate; E) solution blocker such as paraffin; F) absorb accelerator such as quaternary ammonium compound; G) wetting agent such as spermol and glyceryl monostearate; H) adsorbent such as Kaolin and bentonite and i) lubricant such as Pulvis Talci, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulphate and their mixture.Under the situation of capsule, tablet and pill, also can comprise buffer agent in the said dosage form.
Supply Orally administered liquid dosage form to comprise the acceptable Emulsion of physiology, solution, suspensoid, syrup and elixir.Liquid dosage form also can contain this area inert diluent commonly used except that containing active component; For example water or other solvents; Solubilizing agent and emulsifying agent be ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzylalcohol, benzyl benzoate, propylene glycol, 1,3 butylene glycol, dimethyl formamide, oils (particularly Oleum Gossypii semen, Oleum Arachidis hypogaeae semen, Semen Maydis oil, germ oil, olive oil, Oleum Ricini and Oleum sesami), glycerol, oxolane alcohol, Polyethylene Glycol and the fatty acid ester of sorbitan and their mixture for example.
Since people such as nineteen eighty-three Marshall isolate Hp; Domestic and international many scholars have carried out a large amount of research to Hp; Find to eradicate the infection of Hp and can treat chronic gastritis, reduce peptic ulcer relapse rate, block or delay further developing of gastric mucosa atrophy and intestinal epithelial metaplasia.Press down and kill the basic principle that Hp becomes the medical treatment Hp of Gastroenterology dept. related diseases.Developed multiple therapeutic scheme to Hp for many years, standard scheme is that PPI adds two kinds of antibiotic triple therapies at present.But when infecting with antibiotic therapy Hp, the interior normal flora of body also is killed or suppresses, and causes the dysbacteriosis at gastrointestinal tract, pars oralis pharyngis, vagina and each position of skin, causes superinfection.Conventional triple therapy descends to its eradication rate gradually.Therefore seek the alternative triple therapy of suitable medicine and seem particularly important.
Herba Polygoni Capitati is the conventional Chinese medicine of minority area, entering national essential drugs catalogue in 2000.Be that " six big Miao Ethnomedicine " and the Guizhou Tenth Five-Year Plan Period emphasis that Guizhou Province's modernization of Chinese medicine was given priority to before 2010 cultivated one of kind in " the seven big Chinese medicine industrial chains " that develops.Isolated organic compound is individual more than totally six ten from the Herba Polygoni Capitati herb at present, mainly contains flavonoid, aldehyde, ketone, alcohols and terpenoid, and main effective ingredient is gallic acid and flavonoid.Be mainly used in symptoms such as heat-clearing and toxic substances removing, inducing diuresis for treating stranguria syndrome, pyelonephritis, lithangiuria, cystitis, dysentery, rheumatalgia, traumatic injury, urinary tract infection, skin infection eczema at present.
Although people know, the water extract of Herba Polygoni Capitati all has certain antibiotic vigor in vivo and in vitro, especially gonococcus is had stronger antibiotic vigor, (the minimal inhibitory concentration scope is 8-32g/L, and meansigma methods is 11.2g/L).Secondly staphylococcus aureus, staphylococcus epidermidis, escherichia coli, dysentery bacterium, Bacillus proteus and Klebsiella Pneumoniae also there is stronger antibiotic vigor.Bacillus fragilis in part fungus and the anaerobe, dyspepsiacoccus, peptostreptococcus and propionibacterium acnes, propionibacterium granulosum etc. all had certain antibacterial action.Yet the inventor finds that unexpectedly Herba Polygoni Capitati is effective for this intractable pathogenic microorganism of helicobacter pylori and caused associated conditions thereof.
The present invention adopts agar dilution to carry out antibacterial activity test.Reliable and stable for experimental result, strict experiment contrast, repetition and parallel laboratory test are set up in this experiment, and promptly each sample all carries out three identical experiments continuously, and each experiment is all inoculated two flat boards to each concentration at least.The result shows, three unanimities as a result, negative control (promptly not adding bacterium) does not have growth, growth control (i.e. not dosing) well-grown, solvent control (only solubilizer does not add sample)) do not see the growth inhibited phenomenon.We find that through the external bacteriostatic experiment of Herba Polygoni Capitati extract it is to two strain helicobacter pylori ATCC700392 and ATCC700824 fungistatic effect obvious (MIC is 4mg/mL).In the antibacterial activity test of Herba Polygoni Capitati extract to clinical isolates strain Hp B-1 type (to the amoxicillin drug resistance), Hp B-2 type (to the clarithromycin drug resistance), Hp B-3 type (to the metronidazole drug resistance), Hp B-4 type (to amoxicillin, clarithromycin, all drug-fast bacterial strain of three kinds of medicines of metronidazole), each 3 strain clinical strain of Hp B-5 type (bacterial strain all responsive) to amoxicillin, clarithromycin, three kinds of medicines of metronidazole; For experimental result reliable and stable; Strict experiment contrast, repetition and parallel laboratory test are set up in this experiment; Each sample all carries out three identical experiments continuously, and each experiment is all inoculated two flat boards to each concentration at least.The result shows; Three unanimities as a result, negative control (promptly not adding bacterium) do not have growth, growth control (i.e. not dosing) well-grown, solvent control (promptly only solubilizer) and do not see that growth inhibited phenomenon, bacterial strain contrast (promptly do simultaneously Hp international standard check order strain ATCC700392) are consistent with the pre-stage test result.
Result of the present invention shows that Herba Polygoni Capitati extract all has stronger vitro inhibition Hp effect to helicobacter pylori international standard order-checking strain ATCC700392 and ATCC700824 two strain bacterium.In addition, has stronger vitro inhibition Hp effect in the experiment of Herba Polygoni Capitati extract to clinical isolates strain Hp B-1 type (to the amoxicillin drug resistance), Hp B-2 type (to the clarithromycin drug resistance), Hp B-3 type (to the metronidazole drug resistance), HpB-4 type (to amoxicillin, clarithromycin, all drug-fast bacterial strain of three kinds of medicines of metronidazole), Hp B-5 type (bacterial strain all responsive) to amoxicillin, clarithromycin, three kinds of medicines of metronidazole.
The present invention is surprisingly found out that through to the experiment of Herba Polygoni Capitati extract antibacterial activity in vitro it has the activity of anti-helicobacter pylori.For example in one embodiment; With Herba Polygoni Capitati extract respectively to two strain helicobacter pylori (Helicobacter pylori; Be called for short H.pylori; Or Hp) ATCC700392 and ATCC700824 carry out external bacteriostatic experiment; Do not have growth, growth control (i.e. not dosing) well-grown, solvent control (promptly only solubilizer) at negative control (promptly not adding bacterium) and do not see under the condition of growth inhibited phenomenon, the high dilution of the sample of growing with integral asepsis be this bacterial strain to the minimum inhibitory concentration of respective sample (minimal inhibitory concentration, MIC).In another embodiment; Herba Polygoni Capitati extract is carried out external bacteriostatic experiment to these five types each 3 strain clinical separation strains respectively; Do not have at negative control (promptly not adding bacterium) that growth, growth control (i.e. not dosing) well-grown, solvent control (promptly only solubilizer) do not see that growth inhibited phenomenon, sample contrast (promptly making phase I H-2-65 sample simultaneously) are consistent with the phase I experimental result, bacterial strain contrast (promptly do simultaneously Hp international standard check order strain ATCC700392) and pre-stage test be as a result under the uniform condition, the high dilution of the sample of growing with integral asepsis is the minimum inhibitory concentration of this bacterial strain to respective sample.The inventor finds: when (1) Herba Polygoni Capitati extract acts on Hp ATCC700392 and ATCC700824 fungistatic effect obviously (MIC is≤4mg/mL).(2) Herba Polygoni Capitati extract is to the fungistatic effect obvious (MIC is 4 μ g/mL) of the clinical separation 3 strain bacterium of Hp B-1 type (to the amoxicillin drug resistance); Fungistatic effect obvious (MIC is 4 μ g/mL) to the clinical separation 3 strain bacterium of Hp B-2 type (to the clarithromycin drug resistance); The fungistatic effect of the clinical separation 3 strain bacterium of Hp B-3 type (to the metronidazole drug resistance) is (MIC is≤2 μ g/mL) obviously; The fungistatic effect of the clinical separation 3 strain bacterium of Hp B-4 type (to amoxicillin, clarithromycin, all drug-fast bacterial strain of three kinds of medicines of metronidazole) is (MIC is≤8 μ g/mL) obviously, and the fungistatic effect of the clinical separation 3 strain bacterium of Hp B-5 type (bacterial strain all responsive to amoxicillin, clarithromycin, three kinds of medicines of metronidazole) is (MIC is≤4 μ g/mL) obviously; (3) DH-2-65, DH-2-24 are to the fungistatic effect of Hp clinical separation strain obviously (MIC is≤4 μ g/mL).Thus, Herba Polygoni Capitati extract all has stronger external fungistatic effect to two strain helicobacter pylori international standards order-checking strain ATCC700392 and ATCC700824 two strain bacterium; Have stronger vitro inhibition Hp effect in the experiment of Herba Polygoni Capitati extract to the clinical isolates strain, particularly can be used to treat and/or prevent and Helicobacter pylori infection diseases associated or disease thereby be expected to become a kind of brand-new antibacterials.
Description of drawings
Fig. 1 has shown that Herba Polygoni Capitati extract is to the external bacteriostatic result of helicobacter pylori.
Fig. 2 has shown that Herba Polygoni Capitati extract handles the Electronic Speculum figure of antibacterial microscopic morphology behind the helicobacter pylori.
The specific embodiment
Further specify the present invention through concrete embodiment/experimental example below, still, be to be understood that into, these embodiment and experimental example are only used for the usefulness of explanation more in detail particularly, are used for limiting in any form the present invention and should not be construed as.
The present invention carries out generality and/or concrete description to the material and the test method that are used in the test.Though for realizing that employed many materials of the object of the invention and operational approach are well known in the art, the present invention still does to describe in detail as far as possible at this.It will be apparent to those skilled in the art that hereinafter, if do not specify that material therefor of the present invention and operational approach are well known in the art.
A, preparation embodiment part
Embodiment 1: preparation Herba Polygoni Capitati aerial parts water extract
Get Herba Polygoni Capitati aerial parts (dry product) 220kg, clean, add 7 times of water gagings, heated and boiled 1.5 hours is filtered, and adds 6 times of water gagings in the medicinal residues, boils 1.0 hours, filters.Merging filtrate, being concentrated into relative density is that 1.2 (20 ℃) obtain extractum, spray drying obtains extract powder 23.1kg (yield 10.4%), is the Herba Polygoni Capitati extract of present embodiment: brown ceramic powder; Every g sample is equivalent to crude drug in whole 8.7g; The employing spectrophotometer method is measured, flavones content: 18.21mg/g, gallic acid content: 17.82mg/g.
Get 1 part of above extract powder, add 2 parts of starch, 2 parts of microcrystalline Cellulose, mix homogeneously, encapsulated, be pharmaceutical composition of the present invention.
Embodiment 2: preparation Herba Polygoni Capitati herb water extract (spray drying)
The method of reference implementation example 1, difference are to replace the Herba Polygoni Capitati aerial parts to extract with Herba Polygoni Capitati herb (bright article), get the Herba Polygoni Capitati extract of present embodiment.Yield 8.12%.
Embodiment 3: preparation Herba Polygoni Capitati root 95% ethanol extraction
Get Herba Polygoni Capitati dry root 10kg, clean, put in the rustless steel concentration tank, add 95% ethanol of 7.5 times of amounts, reflux, extract, 1.5 hours is filtered.Medicinal residues add 7.5 times of amount 95% ethanol, and reflux, extract, 1.0 hours is filtered.Merge filtrating twice, concentrate extractum, drying under reduced pressure obtains the present embodiment extract, 0.34kg.
Embodiment 4: preparation Herba Polygoni Capitati stem 75% ethanol extraction
The method that reference implementation example 3 is identical, difference is that the dry stem of Herba Polygoni Capitati is extracted with 75% ethanol, must the present embodiment extract.Yield 5.74%.
Embodiment 5: preparation headdress flower Folium Polygonum 60% ethanol extraction
The method that reference implementation example 3 is identical, difference is that the Herba Polygoni Capitati dried leaves is extracted with 60% ethanol, must the present embodiment extract.Yield 8.62%.
Embodiment 6: preparation Herba Polygoni Capitati seed 30% ethanol extraction
The method that reference implementation example 3 is identical, difference is that the Herba Polygoni Capitati dry seed is extracted with 30% ethanol, must the present embodiment extract.Yield 13.4%.
Embodiment 7: preparation Herba Polygoni Capitati soaking with sugar thing
Get Herba Polygoni Capitati aerial parts (dry product), be ground into fine powder, mix (1:1, weight) with saturated sucrose solution and mix (attention prevents growth of microorganism), place more than 3 months.The mixture of placing 3 months makes solid-liquid separation through extruding, and makes the solid content water content be lower than 15%, and the gained leaching liquid is used for biological test example part of the present invention as extract of the present invention.The result shows the effectiveness of this leaching liquid in the hereinafter Test Example, shows that medicinal material of polygonum capilalum can direct (for example direct and sugar is mixed and made into honeyed pill) be used for the purposes that the present invention expects.
Embodiment 8: preparation Herba Polygoni Capitati herb 7% ethanol extraction
Get Herba Polygoni Capitati herb 10kg, clean, put in the rustless steel concentration tank, add 7-8 and doubly measure 80% ethanol, reflux, extract, 1.5 hours is filtered.Medicinal residues add 5 times of amount 60% ethanol, and reflux, extract, 1.5 hours is filtered.Merge filtrating twice, concentrate extractum, drying under reduced pressure obtains extract 0.74kg.
Embodiment 9: preparation Herba Polygoni Capitati herb water decoction-alcohol sedimentation solution powder
Get Herba Polygoni Capitati herb 10kg, clean, add 350kg water, heated and boiled 1.5 hours shifts supernatant, adds 150kg water in the residue, boils 1.0 hours.Merge decoction liquor, filtering and concentrating to relative density is that 1.04 (24 ℃) get extractum 16kg.Add 95% ethanol and transfer to that to contain alcohol amount be 60%, quiet to 24 hours, obtain solution.Add 95% ethanol to deposition and transfer to that to contain the alcohol amount be 60%, quietly obtained solution to 24 hours, merge solution twice, fling to ethanol, 80 ℃ of drying under reduced pressure get Herba Polygoni Capitati herb water decoction-alcohol sedimentation solution powder 0.78kg, as the extract of present embodiment.
Embodiment 10: preparation Herba Polygoni Capitati herb water decoction-alcohol sedimentation precipitated powder
Get Herba Polygoni Capitati herb 10kg, clean, add 350kg water, heated and boiled 1.5 hours shifts supernatant, adds 150kg water in the residue, boils 1.0 hours.Merge decoction liquor, filtering and concentrating to relative density is that 1.04 (24 ℃) get extractum 16kg.Add 95% ethanol and transfer to that to contain alcohol amount be 60%, quiet to 24 hours, obtain solution.Add 95% ethanol to deposition and transfer to that to contain the alcohol amount be 60%, quietly obtained solution to 24 hours, merge solution twice, fling to ethanol, 80 ℃ of drying under reduced pressure get Herba Polygoni Capitati herb water decoction-alcohol sedimentation solution powder 0.78kg; Be deposited in 80 ℃ of drying under reduced pressure by 16kg extractum with the post-processing step gained, get Herba Polygoni Capitati herb water decoction-alcohol sedimentation precipitated powder 0.49kg, as the extract of present embodiment.
Embodiment 11: the former medicated powder carbon dioxide supercritical fluid extraction of preparation Herba Polygoni Capitati extract
Get the former medicated powder 10kg of Herba Polygoni Capitati aerial parts, clean, drop in the supercritical extraction reactor; To extraction kettle and the heating of two extraction-containers, basin is cooled off, when temperature reaches predetermined temperature; Open dioxide bottle and supply gas, when pressure reaches predetermined pressure, the beginning cycling extraction; Regulate flow, and add entrainer, constant temperature and pressure extraction 2 hours.The liquid concentrating under reduced pressure that obtains is obtained extractum 0.17kg, as the extract of present embodiment.
Embodiment 12: preparation Herba Polygoni Capitati medicinal residues carbon dioxide supercritical fluid extraction extract
Get Herba Polygoni Capitati medicinal residues (total medicinal residues of embodiment 1 gained and the total medicinal residues of embodiment 8 gained are with the mixture of weight ratio 1:1) 10kg, drop in the supercritical extraction reactor, to extraction kettle and two extraction-container heating; Basin is cooled off, when temperature reaches predetermined temperature, open dioxide bottle and supply gas; When pressure reached predetermined pressure, the beginning cycling extraction was regulated flow; And the adding entrainer, constant temperature and pressure extraction 2 hours.The liquid concentrating under reduced pressure that obtains is obtained extractum 0.131kg.
Embodiment 13: preparation Herba Polygoni Capitati medicinal residues carbon dioxide supercritical fluid extraction extract
Get Herba Polygoni Capitati aerial parts (dry product) 30kg, add the water of 8 times of amounts, between 80-100 ° of C, decocted 60 minutes, extracting solution enters precipitating jar; In decoction pot, add the water of 4 times of amounts of medical material again, between 80-100 ° of C, decocted 60 minutes, extracting solution enters precipitating jar and merges with extracting solution last time, gets supernatant after waiting to clarify and sends into vacuum concentration pan; Under 60-80 ° of C, be evaporated to paste, then this paste sent in the ethanol extraction pot, measure 65% ethanol extractions 2 times with 3 times; Again ethanol extract is sent in the vacuum concentration pan, under 70-90 ° of C, removed ethanol, concentrating under reduced pressure; Drying promptly gets the present embodiment extract, yield 3.82%.
Embodiment 14: the preparation Herba Polygoni Capitati extract
Herba Polygoni Capitati aerial parts (dry product) 10kg adds 80 liters in water, reflux, extract, 2 times, and each 2h, merge extractive liquid,, hold over night, centrifugal.Macroporous adsorbent resin AB-8 (10kg) on the filtrating with 2 column volumes of washing, discards eluent earlier, and reuse 85% ethanol is washed 3 column volumes, collects eluent, and constant pressure and dry gets Herba Polygoni Capitati extract.
Through detecting, it is 15% that this extract contains total flavones, and gallic acid is 2.5%.
Embodiment 15: the preparation Herba Polygoni Capitati extract
Herba Polygoni Capitati aerial parts (dry product) 10kg adds 10 times of amount 50% ethanol, reflux, extract, 3 times, each 1.5h; Merge extractive liquid,, decompression recycling ethanol to ethanol content is lower than 10%, and last macroporous adsorbent resin NKA-9 is earlier with 2 column volumes of washing; Discard eluent, 2 column volumes of reuse 10% ethanol elution discard eluent, and reuse 80% ethanol is washed 3 column volumes; Collect eluent, drying under reduced pressure gets Herba Polygoni Capitati extract.
Through detecting, it is 41% that this extract contains total flavones, and gallic acid is 11%.
Embodiment 16: the preparation Herba Polygoni Capitati extract
Herba Polygoni Capitati aerial parts (dry product) 10kg adds 10 times of amount 95% ethanol, reflux, extract, 2 times, each 2h; Merge extractive liquid,, decompression recycling ethanol to ethanol content is lower than 10%, last macroporous adsorbent resin HPD400; With 2 column volumes of washing, discard eluent earlier, reuse 90% ethanol is washed 2 column volumes; Collect eluent, spray drying gets Herba Polygoni Capitati extract.
Through detecting, it is 39% that this extract contains total flavones, and gallic acid is 7%.
Embodiment 17: the preparation Herba Polygoni Capitati extract
Herba Polygoni Capitati aerial parts (dry product) 10kg adds 10 times of amount 95% ethanol, reflux, extract, 2 times, each 2h; Merge extractive liquid,, decompression recycling ethanol to ethanol content is lower than 10%, last macroporous adsorbent resin HPD100; With 2 column volumes of washing, discard eluent earlier, reuse 90% ethanol is washed 2 column volumes; Collect eluent, drying under reduced pressure gets Herba Polygoni Capitati extract.
Through detecting, it is 32% that this extract contains total flavones, and gallic acid is 8%.
Embodiment 18: the preparation Herba Polygoni Capitati extract
Herba Polygoni Capitati aerial parts (dry product) 10kg adds 8 times of water gagings, reflux, extract, 2 times, and each 2h, merge extractive liquid,, hold over night, centrifugal.Macroporous adsorbent resin ADS-17 on the filtrating with 2 column volumes of washing, discards eluent earlier, and 2 column volumes of reuse 10% ethanol elution discard eluent, and reuse 90% ethanol is washed 2 column volumes, collects eluent, and drying under reduced pressure gets Herba Polygoni Capitati extract.
Through detecting, it is 37% that this extract contains total flavones, and gallic acid is 9%.
B, biological test example part
Test Example 1: Herba Polygoni Capitati extract (embodiment 1) is to helicobacter pylori type strain and clinical branch
Antibacterial activity from bacterial strain detects
1) experimental strain
Reference culture:Two used strain bacterial strains are helicobacter pylori ATCC700392 and helicobacter pylori ATCC700824 international standard order-checking strain, and available from ATCC (American Type Culture Collecti), passage number is in 10 generations.
The clinical isolates strain:Be the strain of helicobacter pylori clinical isolates; All be that the Guiyang Medical College Digestive System Department will be done gastroscopy and turn out to be peptic ulcer and chronic gastritis; Biopsy mucosa RUT is determined as male patient under the mirror simultaneously, with the mucosa separation Hp of the gastric antrum portion bacterial strain of its biopsy.The authentication method of internationally recognized helicobacter pylori is adopted in the evaluation of Hp bacterial strain, is divided into morphology, urease, oxidase, hydrogen peroxide test, serological test.Clinically be separated to five kinds of bacterial strains (name) and characteristic is respectively:
Hp B-1 type: it is to the amoxicillin drug resistance,
Hp B-2 type: it is to the clarithromycin drug resistance,
Hp B-3 type: it is to the metronidazole drug resistance,
Hp B-4 type: it is to amoxicillin, clarithromycin, all drug-fast bacterial strain of three kinds of medicines of metronidazole,
Hp B-5 type: the bacterial strain that it is all responsive to amoxicillin, clarithromycin, three kinds of medicines of metronidazole.
2) some main agents of test use
Colombia's blood agar and brain heart infusion powder derive from Britain OXOID; Aseptic defiber Sanguis caprae seu ovis derives from Beijing swallow and gives birth to the rich bio tech ltd of political affairs; Oxidase reagent, urease reagent, catalase reagent and E-test strip derive from Biomerieux SA, and Lyphocin (Fujisawa), amphotericin, sulfanilamide (TMP) and polymyxin B derive from U.S. Sigma company.
3) test specimen
The present invention's part embodiment gained Herba Polygoni Capitati extract.
4) preparation of main agents and material:
4.1) mix antibiotic: the method for by specification is prepared
Lyphocin (Fujisawa) 30mg, TMP25mg, polymyxin B20mg, both sexes rhzomorph 20mg, sterile purified water 100ml.
4.2) preparation of common Colombia blood plate:
The preparation of by specification method takes by weighing Colombia agar basis 8g in triangular flask, place the 250ml conical flask; Add the single water that steams of 180ml, behind 121 ℃ of 20min high pressure steam sterilizations, be cooled to about 56 ℃; In superclean bench, add and mix antibiotic 2ml and aseptic defiber Sanguis caprae seu ovis 20ml, transferring pH value is 7.2, quick pour plate behind the vibration mixing; The about 20ml of every ware puts into 4 ℃ of refrigerators and preserves after the agar cooled and solidified, use in 3 days; Select simultaneously a ware to put into 37 ℃ of incubators at random and cultivate 24h, guarantee that this batch of asepsis growth culture dish can use.
4.3) contain the preparation of sample blood plate:
The sample blood plate preparation of variable concentrations: in conical flask, take by weighing Colombia blood agar powder 3.9g; Add the single water that steams of 89ml; Behind the high pressure steam sterilization, be cooled to about 50 ℃, the blood plate of the different gradient concentrations of each sample adds the respective sample mother solution from high to low successively according to concentration; Making its final concentration is 8mg/mL, 4mg/mL, 1024 μ g/mL, 512 μ g mL, 256 μ g/mL, 128 μ g/mL, 64 μ g/mL, 32 μ g/mL; Add the aseptic defiber Sanguis caprae seu ovis of 1ml mixing antibiotic and 10ml simultaneously, quick pour plate (plate diameter is 90mm) can use after the agar cooled and solidified behind the vibration mixing.
4.4) containing the preparation (solvent control) of solvent blood plate: method is with the preparation that contains the sample blood plate, and the dimethyl sulfoxine or the dehydrated alcohol that promptly add respective volume substitute the sample mother solution, then need not prepare as solvent with distilled water.
5) experimental technique
5.1) the recovery cultivation of helicobacter pylori type strain and the evaluation of bacterial strain
From-80 ℃ of refrigerators, take out helicobacter pylori ATCC700392 and helicobacter pylori ATCC700824 reference culture; Place 37 ℃ of water baths to dissolve; Getting bacterium liquid with the inoculating loop libation at an ancient wedding ceremony evenly coats on the antibiotic Colombia of the include mixed blood plate; Place anaerobism to cultivate box, and in box, place two bags of little aerobic aerogenesis bag (85%N
2, 10%CO
2, 5%O
2), sealing is cultivated 72-96h for rearmounted 37 ℃.This two strains reference culture is carried out cultural character, Gram's staining, urease evaluation, catalase evaluation, oxidase evaluation.
5.2) bacterium liquid preparation: the bacterium colony on the blood plate or lawn scraped to pre-cooling contain in the 2ml brain heart infusion meat soup pipe; Behind the centrifuge washing three times; Be resuspended in 4 ℃ of brain heart infusion meat soups, after 10 times, 100 times, 1000 times dilutions of this bacterium liquid do, on ultraviolet spectrophotometer, survey the OD600 value of bacterium liquid; OD value and the bacterial concentration of result between 0.1-1.0 has the better linearity relation, and the computing formula of bacterium liquid hold-up is following: bacterium amount/ml=2.2 * 10
8* OD
600Value * extension rate.The dilution of bacterium liquid is obtained 10
8CFU/mL.In 15 minutes, accomplish preparation of bacterium liquid and inoculation, bacterium liquid need remain on 4 ℃ in the seeded process.
5.3) experiment of the antibacterial activity in vitro of Herba Polygoni Capitati extract
5.3.1) coating of bacterium liquid: drawing 200 μ l concentration is 10
8CFU/mL bacterium liquid evenly is coated with at agar surface with L type rod.All be coated with 2 flat boards by each concentration of every kind of sample.Establish negative control (promptly not adding bacterium), growth control (promptly not adding laboratory sample), each two flat board of solvent control simultaneously.
5.3.2) cultivate: method to specifications, place anaerobism to cultivate box, and in box, place two bags of little aerobic aerogenesis bags, seal back 37 ℃ and cultivate observed result behind the 72-96h.Twice of the antibacterial activity in vitro experiment repetition of each sample.
5.3.3) the Herba Polygoni Capitati extract fungistatic effect judges: not having under the condition of growth inhibited phenomenon in negative control (promptly not adding bacterium) asepsis growth, growth control (promptly not adding laboratory sample) well-grown, solvent control, is the MIC of this bacterial strain to respective sample with the high dilution of the sample of integral asepsis growth.
6) result of experiment:
6.1) evaluation of helicobacter pylori
Two strain helicobacter pylori ATCC700392 and ATCC700824 and clinical separation strain place on common Colombia blood plate under little aerobic condition and cultivated 72-96 hour, and bacterium colony is the tip-like water white transparency, and is smooth moistening; Neat in edge, convexity is little water droplet appearance; The lawn canescence, hair oil light.
Biochemical test: urease test is positive, and oxidase test is positive, and catalase test is positive; Under microscope oil mirror, observe, typical sea-gull shape, the S shape, Gram's staining is negative.
6.2) antibacterial activity in vitro of Herba Polygoni Capitati extract test experimental result sees table 1.
The extract of table 1, the embodiment of the invention 1 is to the external antibacterial result of helicobacter pylori (MIC)
In the parallel test of present embodiment; Simultaneous verification amoxicillin, clarithromycin, metronidazole three sensitivity to seven kinds of helicobacter pylori in the last table; Gained basically identical in result and common the detection; Promptly three kinds of medicines are all responsive to ATCC700392 and ATCC700824, and Hp B-1 is to the amoxicillin drug resistance, to other two kinds of medicaments insensitives; Hp B-2 is to the clarithromycin drug resistance, to other two kinds of medicaments insensitives; Hp B-3 is to the metronidazole drug resistance, to other two kinds of medicaments insensitives; Hp B-4 is to amoxicillin, clarithromycin, three kinds of equal drug resistances of medicine of metronidazole; Hp B-5 is all responsive to amoxicillin, clarithromycin, three kinds of medicines of metronidazole.
In addition, each test group antibacterial (ATCC700392) growing state of perusal, the result sees Fig. 1.Wherein Fig. 1 a is the growth control group that antibacterial grows in culture medium, shows that bacterial growth is normal, is homodisperse small particles; Fig. 1 b is the solvent matched group that antibacterial grows in the culture medium of having added the solvent that is used for preparating liquid, shows that bacterial growth is normal, is homodisperse small particles; Fig. 1 c is the plate that does not add antibacterial in the parallel test, and negative matched group shows no bacterial growth, the small particles of no typical bacteria growth; Fig. 1 d, 1e, 1f are respectively that the embodiment of the invention 1 extract adds to back 2 days, 3 days, 4 days macroscopic results in the plate of bacterial growth; Being presented at 2 days antibacterials obviously lacks than the growth control group; The discrete antibacterial small particles that is dispersed in only appearred on the 3rd day; And can not see antibacterial fully by the 4th day, similar with the plate of negative control group.
In addition, more than in the test, in ATCC700392 bacterium group, get blank 0 day, blank 4 days, Herba Polygoni Capitati is handled 2 days, Herba Polygoni Capitati and is handled 4 days culture, carries out electron microscopic examination respectively, and the result sees Fig. 2 a, 2b, 2c and 2d respectively.Variform thalline smooth surfaces such as visible from figure, that the antibacterial of 0 day culture of blank is is shaft-like, bagel appearance, U type, neat in edge, (Fig. 2 is a) for the electron density homogeneous; The antibacterial of 4 days cultures of blank is variforms such as rod-short, bagel appearance, U type, thalline smooth surface, neat in edge (Fig. 2 b); The antibacterial that Herba Polygoni Capitati is handled 2 days cultures is variforms such as rod-short, U type, bagel appearance, has part thalline surface that performances (Fig. 2 c) such as depression, disappearance are arranged; It is serious that the antibacterial that Herba Polygoni Capitati is handled 4 days cultures is form part thalline surface depressions such as elongated rod shape, screw shaped, an end curve inwardly, and division (Fig. 2 d) appears in part thalline (like the rightmost bacterium) from the centre.
Test Example 2: Herba Polygoni Capitati extract is anti-to helicobacter pylori type strain and clinical isolates strain
Bacterium is active to be detected
Basically the method for reference test example 1; Extract obtained with embodiment 2-18 respectively is reagent; Test the antibacterial activity of these extracts to ATCC700392, ATCC700824, Hp B-1, Hp B-2, Hp B-3, Hp B-4, Hp B-5; As a result all extracts to the MIC value of these seven kinds of helicobacter pylori between 0.05 ~ 8mg/mL; The MIC value of seven kinds of helicobacter pylori that for example embodiment 2-10,17 extracts are right is between 1 ~ 8mg/mL, and the MIC value of seven kinds of helicobacter pylori that embodiment 11-16,18 extracts are right is between 0.05 ~ 2mg/mL.
Test Example 3: experiment in the body of Herba Polygoni Capitati extract (embodiment 1 is extract obtained)
Through building the model of Helicobacter pylori infection mice, with after the Herba Polygoni Capitati treatment, observe the elimination situation of Hp and the improvement situation of stomach lining inflammation then, judge that Herba Polygoni Capitati suppresses or kill the effect of Hp in vivo.Experimental strain selection standard strains A TCC700392 and SS1, laboratory animal is selected SPF level BALB/c mouse for use.Experimental technique is following:
1) building animal model divides into groups: type strain 700392 and SS1: negative control group, positive controls and experimental group.
2) recovery bacterial strain: recovery reference culture ATCC700392 and SS1, and go down to posterity once, be respectively to animal filling stomach and prepare.
3) animal pretreatment: to animal marshalling numbering; Jejunitas, 24h runs out of rice and fuel; 50% ethanol 0.3ml irritates stomach, continues jejunitas running out of rice and fuel.
4) infect Hp: behind the alcohol pre-treatment 24h with 10
9Self-regulated bacterium liquid 0.5ml irritates stomach; 0.5ml/ the only upper and lower noon each 1 time feeds 1 time to irritate with dosage with concentration every other day the morning again, matched group is irritated with aseptic meat soup and is fed, and supplies food, water behind the 4h.Make the animal grouping carry out administration after infecting for 8 weeks.Get the part animal in addition;, last puts to death mice respectively after infecting the 4th week of back, the 8th week and the 12nd week; Observe the mouse model success of whether building Helicobacter pylori infection; And infect and whether to continue to exist, observation item is following: (1) is put to death the back and is taken out Mus gastric antrum portion mucosal tissue, and half is cultivated, smear and the test of the RUT scraps of paper; (2) animal eyeball blood-letting, separation of serum is preserved the ELISA test for-20 ℃ and is detected anti-Hp antibody; (3) second half mucosal tissue is done HE dyeing to observe the pathological changes such as inflammation degree of its Hp field planting situation and mucosal tissue.The result shows and infects the back all animals modelings success of 8 weeks and still continue to exist to infect during to 12 weeks.
5) Drug therapy and detection: make the animal grouping carry out administration, every group of 20 animals after infecting for 8 weeks.Experimental group gives embodiment 11 extracts, 250mg/kg/d (5% CMC-Na solution dissolving/suspendible), continuous 14 days; Positive controls gives the amoxicillin, 250mg/kg/d (5% CMC-Na solution dissolving/suspendible), continuous 14 days), negative control group gives the CMC-Na solution with volume.Whether 4 weeks observation mice stomach symptoms after treatment finishes are improved and whether helicobacter pylori is eradicated.Perusal, the result shows that in the test of every kind of bacterial strain, the gastric mucosa of animal in experimental group and the positive controls more than 80% is normal, no ulcer, the demonstration helicobacter pylori is eradicated, and negative control group all animals stomach all has tangible ulcer surface.
Test Example 4: Herba Polygoni Capitati extract infects the gastric mucosal protective effect of C57BL/6 mice to Hp
1, materials and methods
Bacterial strain: helicobacter pylori ATCC700392 international standard order-checking strain, available from ATCC (American Type Culture Collecti), passage number is in 10 generations.Helicobacter pylori Hp Sydney strain SS2000 is so kind as to give by infectious disease institute of Chinese Center for Disease Control (CDC) Zhang Jianzhong, professor He Lihua.Animal: 70 SPF level C57BL/6 mices; 6 ~ 8 ages in week; ♀ 35;
body weight (20 ± 5) g is provided by Medical University Of Chongqing's Experimental Animal Center, the quality certification number: SYXK (Chongqing) 2007-0001.
Medicine: Herba Polygoni Capitati extract powder; Brown ceramic powder, crude drug content are 8.72g/g, flavones content: 18.2mg/g; Gallic acid content: 17.8mg/g; Powdered extract powder according to the method for preparing of " Pharmacopoeia of People's Republic of China 2010 version one one " " the clear granule of pyretic stranguria " kind obtains does not add adjuvant, below available code name HL-1112 represent this medicine.
During use, can be dissolved into concentrated solution (for example 320mg/mL) with aseptic double-distilled water, 4 ℃ of preservations are subsequent use, face with dilution.
2, experimental technique
(1) Miao Ethnomedicine HL--1112 is to the detection of Hp minimum inhibitory concentration (MIC)
The preparation of Colombia's blood agar plate: take by weighing Colombia blood agar powder 3.9g, add the 89mL deionized water, (121 ℃ of autoclavings; 20min) after the processing; Add the aseptic defiber Sanguis caprae seu ovis of 10mL (10%) when treating that agar is cooled to 50 ℃～55 ℃, 1mL (1%) mixes antibiotic and fully palms off as, being poured into diameter is in the aseptic plate of 90mm, making agar thickness is 3mm～4mm; And get a ware at random and place and cultivate 24h in 37 ℃ of calorstats and do sterility test, it is subsequent use that all the other all put into 4 ℃ of refrigerators.
The cultivation of helicobacter pylori SS2000 and ATCC 700392: from-80 ℃ of refrigerators, take out bacterial strain to be measured-helicobacter pylori SS2000 and ATCC 700392; Be poured in Colombia's blood agar plate after the room temperature dissolving; Coating is evenly cultivated 72h (5%O in 37 ℃ of calorstats
2, 10%CO
2, 85%N
2, relative humidity is more than 95%), observe the bacterial growth situation and carry out the Hp identification experiment: Gram, oxidase, catalase, urease experiment; With identification experiment be male antibacterial go down to posterity cultivate behind the 72h repeated observation bacterial growth situation and and carry out the Bacteria Identification experiment, antibacterial is changeed once more kind in Colombia's blood agar plate, cultivates 72h.
The configuration of HL-1112 medicine plate: take by weighing 17.55g Colombia solid agar powder and be dissolved in the 378mL deionized water; After being sub-packed in 9 conical flask inner high voltage sterilizations; Add 5mL (10%) defiber Sanguis caprae seu ovis when treating that culture medium is cooled to 50～55 ℃ of left and right sides, 0.5mL (1%) mixes antibiotic, adds corresponding dilution medicinal liquid 2.5mL again, behind the abundant mixing; Pour in 2 aseptic plates (90mm diameter), solidify back 4 ℃ of preservations.The dilution factor of Miao Ethnomedicine HL-1112 solution and the corresponding dull and stereotyped concentration that contains see the following form.
Drug sensitive experiment: the helicobacter pylori that will cultivate the 72h cell age heart infusion broth of requiring mental skill prepares bacteria suspension, allocates its concentration 3 * 10
8CFU/mL, aseptic cotton carrier pick bacteria suspension and evenly coat on the medicine culture dish and blank culture dish that contains variable concentrations, and each drug level is smeared two plates, place little aerobic environment to cultivate 72h for 37 ℃.Bacterial growth is good on blank culture dish; Miao Ethnomedicine HL-1112 is under the situation of 4mg/mL to the MIC of Hp ATCC700392; With the minimum drug level of not seeing bacterial growth on the pastille culture dish is the minimal inhibitory concentration (MIC) of Miao Ethnomedicine HL-1112 to Hp SS2000, and the growth antibacterial is cooked Gram and biochemical identification experiment.
(2) modelling of helicobacter pylori infections mice chronic gastritis
Helicobacter pylori is cultivated: takes out frozen Hp SS2000 bacterial strain at-80 ℃, treat the room temperature dissolving after, be poured on Colombia's blood agar culture-medium, after the mixing, the plate of inoculating is put into three gas incubator (5%O
2, 10%CO
2, 85%N
2), humidity keeps more than 90%, cultivates 72h, twice of continuous passage.
Bacterium liquid preparation: the C57BL/6 adaptability raised for 1 week before the modeling, after animal is divided into normal group (20) and modeling group (50) by body weight, male and female stratified random; Hp cultivates the 72h results, scrapes and gets bacterium colony, and in suspendible and the aseptic brain heart infusion meat soup, ultraviolet spectrophotometer is measured bacterial concentration, and when A600=1, bacterial concentration is 2.2 * 10
8Cfu/mL is with bacterial concentration modulation 1 * 10
9Cfu/mL, 4 ℃ of preservations.
Hp inoculates mice: introduce inoculated with Hp according to document; Concrete steps are following: water 12h is prohibited in fasting, at first irritates to mice and raises 0.3mL 50% ethanol, the Hp reference culture SS2000 bacterium liquid 0.5mL (1 * 10 that inoculation every other day prepares
9Cfu/mL), 1d irritates stomach 5 times altogether at interval, and normal group replaces with the aseptic brain heart infusion meat soup of equivalent; Fasting before all mouse stomaches are handled, taboo water 12h, fasting behind the filling stomach, taboo water 4h; After last was irritated stomach 8w, fasting, fasting 24h randomly drawed 10 mices from normal group and modeling group, dissected immediately after the execution; Take out gastral cavity, cut off along the greater gastric curvature side, aseptic PBS cleans the flushing gastric content; Vertically be divided into 3 parts, wherein 1 block organization's row RUT detects, and carries out the capable Hp of doubling dilution after the homogenate of 1 block organization and cultivates; 1 block organization is through FFPE in addition, and histopathology and Hp inspection is carried out in section back row HE and Giemsa dyeing; Suspicious bacterium colony Gram is had typical characteristic in BIAO and BEN cultivation back and the equal positive of urease experiment, catalase test and oxidase test is judged to be the Hp infection; Whether histopathology is judged according to the diagnostic criteria of chronic gastritis Sydney, adopts the sxemiquantitative point system that Hp density, chronic inflammatory disease, inflammation activeness, atrophy and intestinal epithelial metaplasia are marked, successful with the inflammation modeling.
Sample disposal:
(a) Hp field planting standard: RUT experiment, fresh mice mucosa tissue is put into urease reagent, tissue is put into back 30min reagent and is become red by orange colour or aubergine person is the positive.Giemsa dyeing, paraffin section goes in the xylene to dewax, ethanol gradient dehydrations at different levels, the 30min that dyes in the 2%Giemsa dyeing liquor, xylene is transparent, mounting, the Hp thalline is navy blue.The tissue culture of Hp: behind the weighing mucosal tissue, homogenate is got 200 μ L and evenly is coated with and blank dull and stereotyped cultivation of Colombia's blood agar, and behind cultivation 5 ~ 7d, the capable urease of bacterium colony, catalase and the oxidase of turning out carried out Hp identify, and smear for microscopic examination Hp form.Two positives are the Hp field planting positive among the three.
(b) Hp plantation density: behind the weighing mucosal tissue, homogenate goes homogenate to do 10 then
-1Serial dilution, each dilution factor are got 200 μ L and evenly are coated with and blank dull and stereotyped cultivation of Colombia's blood agar, and behind cultivation 5 ~ 7d, the viable count in the counting flat board is converted into the viable count (cfu) in every gram gastric tissue then, and plantation density is with the expression of Igcfu/g tissue;
(c) mice gastric tissue pathology detect: piece of tissue is conventional fixing with 10% formaldehyde, ethanol dehydration, and xylene is transparent, FFPE, 4 μ m section.60 ℃ of roasting sheet 2h.HE dyeing: tissue slice dyes in the haematoxylin dyeing liquid through dewaxing and the dehydration of gradient Ethanol Treatment, hydrochloride alcohol color separation, the color separation of ammonia ethanol, flushing back Yihong dyeing 5min, conventional dehydration, transparent, mounting.Karyon is dyed blueness, kytoplasm and Hp levelling pinken.
(d) criterion of pathological change: the gastritis of mice is with reference to the classification method of people's gastritis (2000 sorting technique in national chronic gastritis seminar common recognition suggestion), and the degree of depth of soaking into coat of the stomach according to the order of magnitude of chronic inflammatory cells (lymphocyte, plasma cell and eosinophilic granulocyte) is divided into 3 grades and score: NIP 0 minute; Inflammation is confined to mucosa shallow-layer 1/3 and thinks for slightly counting 1 fen; Reaching 2/3 deeply is moderate meter 2 minutes; Surpass 2/3 or holostrome and the intensive person of cell be severe meter 3 minutes.Inflammation activeness score: lamina propria had the neutrophilic granulocyte meter that is dispersed in 1 minute, and lamina propria has more neutrophilic granulocyte meter 2 minutes, and lamina propria has a large amount of neutrophilic granulocyte meters 3 minutes.
(e) modeling success criterion: the mice gastric has Hp field planting and gastric mucosa the chronic inflammatory disease pathological change to occur to be judged as the modeling success.
(3) Miao Ethnomedicine HL-1112 therapeutic intervention Hp infecting mouse chronic gastritis
(a) mice group: modeling group mice is divided into 4 groups, 10 every group, is respectively dose groups and HL-1112 low dose group among model group, HL-1112 high dose group, the HL-1112.
(b) dosage regimen: Miao Ethnomedicine HL-1112 extractum; Crude drug content is that 8.72g/g gets; Can't measure its LD50; Miao Ethnomedicine HL-1112 to the maximum tolerated dose of mice be its 1/5MTD of 249.0g/kg/d, 1/10MTD, 1/20MTD respectively as high, medium and low group of dosage, use distilled water to be made into concentration and be the high dose of 49.8g/kg/d, the middle dosage of 24.9g/kg/d and the low dosage of 12.45g/kg/d.Begin gastric infusion after the modeling success, model group all gives aseptic PBS 0.5mL, and every of the high, medium and low dose groups of Miao Ethnomedicine HL-1112 gives the HL-1112 aqueous solution 0.5mL of high, medium and low dosage respectively.Below respectively organize and irritate stomach equal every day 1 time, successive administration 2w.Blank control group: the normal raising, do not irritate stomach.
(c) observe the curative effect: treatment finishes back 4w, and experiment mice cervical vertebra dislocation method is put to death, and the taking-up gastric tissue of cutting open the belly is cut open along the greater gastric curvature stringer; Remove gastric content with sterilization PBS washing, get gastric antrum portion lesser curvature side tissue, vertically be divided into 3 parts; Wherein 1 block organization's row RUT detects, and carries out the capable Hp of doubling dilution after the homogenate of 1 block organization and cultivates, and 1 block organization places 10% formalin fixing in addition; FFPE, histopathology and Hp inspection is carried out in section back row HE and Giemsa dyeing.Before mice was put to death, water 24h was prohibited in fasting.
(d) statistical analysis: measurement data uses SPSS 15.0 software kits to carry out statistical analysis with " mean standard deviation " expression.Adopt each group difference of F inspection statistics, relatively adopt the q check in twos.
3, experimental result
(1) cultivation of Hp bacterial strain and evaluation
Hp international standard strain SS2000 after cultivating 72h on Colombia's blood agar plate, the tiny tip-like, smooth moistening, translucent glossy that is of bacterium colony.Microscopy behind the smear Gram, antibacterial are the G-bacillus of helical form, S shape, arc or sea-gull shape, and biochemical identification experiment urease, catalase, oxidase are all positive.
(2) Miao Ethnomedicine HL-1112 is to the detection of Hp minimum inhibitory concentration (MIC)
Good with bacterial growth in the blank plate; Under the contrast of Miao Ethnomedicine HL-1112 to the minimum inhibitory concentration MIC=4mg/mL of Hp international standard order-checking strain ATCC 700392; Experiment repetition 3 times; It is good all to observe Hp growth conditions in the pastille plate of 0.125mg/mL, 0.5mg/mL, 1mg/mL, and it is thin in the pastille plate of 2mg/mL, to grow, and in the plate of 4mg/mL, 8mg/mL and 16mg/mL, not seeing has bacterial growth.So Miao Ethnomedicine HL-1112 is 4mg/mL to the minimum inhibitory concentration MIC of Hp SS2000.
(3) Hp field planting and distribution
The urease experiment of normal group animal gastric antrum, body of stomach and DM, Giemsa dyeing and gastric mucosa Hp cultivation results all show feminine gender.After inoculated with Hp during 8w; Model group mice gastric antrum, gastric body mucosa urease-positive rate, Giemsa dyeing show that field planting rate, Hp cultured positive rate are 100%; Giemsa dyeing is presented at the field planting that body of stomach and gastric antrum portion all can be observed antibacterial; Maximum with the observed field planting antibacterial of the mucomembranous gland at gastric antrum position, also visible a large amount of antibacterials in gastric gland surface and upper strata mucus.After HL-1112 intervenes, its high, medium and low dose groups mice histopathology Giemsa dyeing, major part does not see that the Hp field planting organizes at gastric antrum.
(4) result of mice histopathologic examination
The gastric mucosa of model group mice occurs and the human similarly pathological change of chronic active gastritis behind the last bacterium liquid filling stomach 8w; Inflammatory cell infiltration appears; The integrity and the seriality of gastric mucosa are damaged; Be between the gastric epithelial cell at center with the pylorus mucosa and the visible a large amount of lymphocytic infiltrations of lamina propria, the centre is mingled with a small amount of neutrophil infiltration and plasmocyte infiltrating, and the inflammation scoring is 2.5 minutes.The gastric mucosa of blank control group mice is complete, the body of gland queueing discipline, and a matter, mucosa lamination are not seen obviously unusual, rare lymphocytic infiltration, pathological score is 0.5 minute.Through statistics, model group and blank control group compare, and the infiltration degree difference of esogastritis sexual cell has the significance meaning.
HL-1112 low dose group mice gastric mucosa is visible, and the cell infiltration that is dispersed on a small quantity, pathological score to be arranged around muscular layer of mucosa on every side with body of gland be 1 ~ 1.5 minute; The middle and high dosage treatment group of HL-1112 mice gastric mucosal lesion is seen the inflammatory cell that minute quantity is arranged between mucous layer and body of gland, and pathological score is 1 minute.It is thus clear that the mice chronic gastritis that HL-1112 causes helicobacter pylori infections has the significant effect of improving.In the other test; With reference to said method; When giving HL-1112, give amoxicillin or omeprazole (the latter two dosage are respectively 10mg/kg/d, 1mg/kg/d) simultaneously; The result shows that comparing pathological score than list with the respective sets of HL-1112 all hanged down 0.5 fen, showed that two types of drug regimen results of use are better.
(5) respectively organize the Hp eradication rate: the result shows, high, medium and low dose groups of HL-1112 and model group more all have significant difference (P < 0.05); The relatively more equal no difference of science of statistics of high, medium and low dose groups of HL-1112 and blank control group (P>0.05); Not statistically significant (P>0.05) relatively in twos between the high, medium and low dose groups of HL-1112 is explained between the high, medium and low dose groups of HL-1112 relatively the eradication rate no significant difference to Hp.
Claims (10)
1. Herba Polygoni Capitati or its extract are used for treating and/or preventing the purposes with the medicine of Helicobacter pylori infection diseases associated or disease in preparation.
2. the purposes of claim 1, it is characterized in that following (a) to (d) each or multinomial:
(a) described Herba Polygoni Capitati is the aquatic foods article or the dry product of Herba Polygoni Capitati;
(b) described Herba Polygoni Capitati is herb, aerial parts, leaf, flower, stem, seed or its combination that is selected from Herba Polygoni Capitati;
(c) described Herba Polygoni Capitati is the aerial parts that is selected from Herba Polygoni Capitati;
(d) described Herba Polygoni Capitati is leaf, flower, stem, seed or its combination that is selected from Herba Polygoni Capitati.
3. each purposes of claim 1 to 2, it is characterized in that following (a) to (c) each or multinomial:
(a) said extract is that Herba Polygoni Capitati water, ethanol, ethanol water or its combination are as solvent, through extracting the extract that obtains; Or Herba Polygoni Capitati is through the extract of carbon dioxide supercritical fluid extraction method acquisition; Further; Said ethanol water is 30 ~ 99% ethanol waters;
(b) said extract is the extract according to the method preparation that comprises the steps: decocted and/or reflux, extract, concentrated extracting solution, drying by medicinal material of polygonum capilalum water, ethanol or ethanol water.Perhaps, wherein said extract obtains with the carbon dioxide supercritical fluid extraction Herba Polygoni Capitati;
(c) said extract is the extract according to the method preparation that comprises the steps: get medicinal material of polygonum capilalum; Add 5 ~ 20 times water, ethanol or ethanol water decocts and/or reflux, extract, 1 ~ 5 time, each 0.5 ~ 5 hour, collecting decoction; Filter; Filtrate decompression is concentrated into the thick paste that relative density is 1.1 ~ 1.5 (25 ° of C), and drying promptly gets.
4. each purposes of claim 1 to 3; Wherein said and Helicobacter pylori infection diseases associated or disease are selected from: gastric mucosa dependency lymphoma, peptic ulcer, gastric ulcer, duodenal ulcer, acute or chronic gastritis, superficial gastritis, atrophic gastritis, gastric cancer, cardiovascular disease, coronary heart disease, arteriosclerosis, cerebral infarction, hypertension, anemia, iron deficiency anemia, recurrent peptic ulcer, gastric mucosa atrophy, intestinal epithelial metaplasia and thrombocytopenic purpura, and their complication.
5. each purposes of claim 1 to 4; Also comprise one or more other medicine in the wherein said medicine; This other medicine is selected from: antimicrobial drug (PCs amoxicillin for example for example; Macrolide is clarithromycin for example, and the nitre imidazoles is metronidazole for example), proton pump inhibitor (for example omeprazole, lansoprazole, pantoprazole), gastric mucosa protectant (for example sucralfate, dioctahedral smectite).
6. be used to treat and/or prevent the pharmaceutical composition with Helicobacter pylori infection diseases associated or disease, wherein comprise Herba Polygoni Capitati or its extract, and optional pharmaceutically acceptable carrier or excipient.
7. the pharmaceutical composition of claim 6, it is characterized in that following (a) to (d) each or multinomial:
Described Herba Polygoni Capitati is the aquatic foods article or the dry product of Herba Polygoni Capitati;
Described Herba Polygoni Capitati is herb, aerial parts, leaf, flower, stem, seed or its combination that is selected from Herba Polygoni Capitati;
Said extract is that Herba Polygoni Capitati water, ethanol, ethanol water or its combination are as solvent, through extracting the extract that obtains; Or Herba Polygoni Capitati is through the extract of carbon dioxide supercritical fluid extraction method acquisition;
Said ethanol water is 30 ~ 99% ethanol waters.
8. the pharmaceutical composition of claim 6 to 7 is characterized in that:
(a) said extract is the extract according to the method preparation that comprises the steps: decocted and/or reflux, extract, concentrated extracting solution, drying by medicinal material of polygonum capilalum water, ethanol or ethanol water.Perhaps, wherein said extract obtains with the carbon dioxide supercritical fluid extraction Herba Polygoni Capitati; And/or
Said extract is the extract according to the method preparation that comprises the steps: get medicinal material of polygonum capilalum; Add 5 ~ 20 times water, ethanol or ethanol water decocts and/or reflux, extract, 1 ~ 5 time, each 0.5 ~ 5 hour, collecting decoction; Filter; Filtrate decompression is concentrated into the thick paste that relative density is 1.1 ~ 1.5 (25 ° of C), and drying promptly gets.
9. each pharmaceutical composition of claim 6 to 8; Wherein said and Helicobacter pylori infection diseases associated or disease are selected from: gastric mucosa dependency lymphoma, peptic ulcer, gastric ulcer, duodenal ulcer, acute or chronic gastritis, superficial gastritis, atrophic gastritis, gastric cancer, cardiovascular disease, coronary heart disease, arteriosclerosis, cerebral infarction, hypertension, anemia, iron deficiency anemia, recurrent peptic ulcer, gastric mucosa atrophy, intestinal epithelial metaplasia and thrombocytopenic purpura, and their complication.
10. each pharmaceutical composition of claim 6 to 9; Wherein also comprise one or more other medicine; This other medicine is selected from: antimicrobial drug (PCs amoxicillin for example for example; Macrolide is clarithromycin for example, and the nitre imidazoles is metronidazole for example), proton pump inhibitor (for example omeprazole, lansoprazole, pantoprazole), gastric mucosa protectant (for example sucralfate, dioctahedral smectite).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210352856 CN102824417B (en) | 2011-09-26 | 2012-09-20 | New method for treating helicobacter pylori related diseases |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110287094 | 2011-09-26 | ||
| CN201110287094.1 | 2011-09-26 | ||
| CN 201210352856 CN102824417B (en) | 2011-09-26 | 2012-09-20 | New method for treating helicobacter pylori related diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102824417A true CN102824417A (en) | 2012-12-19 |
| CN102824417B CN102824417B (en) | 2013-12-25 |
Family
ID=47327863
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210352856 Active CN102824417B (en) | 2011-09-26 | 2012-09-20 | New method for treating helicobacter pylori related diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102824417B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017020862A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Application of polygonum capitatum composition in treating gastritis |
| WO2017020280A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Uses of composition comprising polygonum capitatum and coptis roots in preparation of drugs for treating gastritis |
| WO2017020861A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Application of polygonum capitatum composition in resisting helicobacter pylori |
| WO2017020279A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Uses of composition comprising polygonum capitatum and coptis roots in preparation of drugs for resisting against helicobacter pylori |
| CN110403012A (en) * | 2018-04-27 | 2019-11-05 | 鼎赫生物科技股份有限公司 | A kind of fish needle grass lactone is used to prepare the purposes for the composition for inhibiting the protein of stomach Helicobacter pylori to synthesize |
| CN113413402A (en) * | 2021-08-02 | 2021-09-21 | 内蒙古医科大学附属医院(内蒙古自治区心血管研究所) | Application of plum blossom extract in preparation of medicine for treating helicobacter pylori infection diseases |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481832A (en) * | 2002-09-12 | 2004-03-17 | 贵州威门药业股份有限公司 | Polygonum capitatum extract and preparation method and application thereof |
| CN1672708A (en) * | 2004-03-25 | 2005-09-28 | 一笑堂（湖南）制药有限公司 | Dispersive tablet for treating heat-type stranguria and its prepn |
| CN101940625A (en) * | 2010-09-07 | 2011-01-12 | 中国中医科学院中药研究所 | Preparation method and use of extract |
-
2012
- 2012-09-20 CN CN 201210352856 patent/CN102824417B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481832A (en) * | 2002-09-12 | 2004-03-17 | 贵州威门药业股份有限公司 | Polygonum capitatum extract and preparation method and application thereof |
| CN1672708A (en) * | 2004-03-25 | 2005-09-28 | 一笑堂（湖南）制药有限公司 | Dispersive tablet for treating heat-type stranguria and its prepn |
| CN101940625A (en) * | 2010-09-07 | 2011-01-12 | 中国中医科学院中药研究所 | Preparation method and use of extract |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017020862A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Application of polygonum capitatum composition in treating gastritis |
| WO2017020280A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Uses of composition comprising polygonum capitatum and coptis roots in preparation of drugs for treating gastritis |
| WO2017020861A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Application of polygonum capitatum composition in resisting helicobacter pylori |
| WO2017020279A1 (en) * | 2015-08-05 | 2017-02-09 | 浙江众康药业有限公司 | Uses of composition comprising polygonum capitatum and coptis roots in preparation of drugs for resisting against helicobacter pylori |
| CN110403012A (en) * | 2018-04-27 | 2019-11-05 | 鼎赫生物科技股份有限公司 | A kind of fish needle grass lactone is used to prepare the purposes for the composition for inhibiting the protein of stomach Helicobacter pylori to synthesize |
| CN113413402A (en) * | 2021-08-02 | 2021-09-21 | 内蒙古医科大学附属医院(内蒙古自治区心血管研究所) | Application of plum blossom extract in preparation of medicine for treating helicobacter pylori infection diseases |
| CN113413402B (en) * | 2021-08-02 | 2022-11-04 | 内蒙古医科大学附属医院(内蒙古自治区心血管研究所) | Application of plum blossom extract in preparation of medicine for treating helicobacter pylori infection disease |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102824417B (en) | 2013-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102824417B (en) | New method for treating helicobacter pylori related diseases | |
| CN114053343A (en) | Traditional Chinese medicine composition, preparation method and application | |
| CN105748622A (en) | Probiotic fermented traditional Chinese medicine composition for spasmolysis and analgesia and preparation method and application thereof | |
| CN1682842A (en) | Chinese medicine composition for diminishing-inflammation and detoxication and its preparing method and use | |
| CN101332256B (en) | Traditional Chinese medicine composition for infectious bursal disease and preparation method thereof | |
| CN112587595B (en) | Traditional Chinese medicine composition for clearing heat and relieving exterior syndrome and preparation method thereof | |
| CN102764294B (en) | Cough relieving and sputum eliminating combination and preparation method thereof | |
| CN109966357A (en) | A kind of Traditional Chinese medicine micro-ecological compound preparation and its preparation method and application | |
| CN101244165B (en) | Tablet for treating damp-heat gonorrhoea and preparation thereof | |
| CN106728077B (en) | Composition with functions of regulating intestinal flora structure and preventing and treating constipation and preparation method and application thereof | |
| WO2017020279A1 (en) | Uses of composition comprising polygonum capitatum and coptis roots in preparation of drugs for resisting against helicobacter pylori | |
| WO2017020861A1 (en) | Application of polygonum capitatum composition in resisting helicobacter pylori | |
| CN107334793A (en) | The purposes of wintersweet platymiscium helicobacter pylori resistant | |
| CN1943665A (en) | A Chinese traditional medicinal composition and its preparation method | |
| CN1243443A (en) | Fresh rehmannia root extract for proliferation of bifidobactor and extraction method thereof | |
| CN109820936A (en) | A kind of composition and preparation method thereof for treating pneumonia | |
| CN109432287A (en) | A kind of traditional Chinese medicine oral liquid and preparation method thereof of prevention and treatment poultry excessive heat in the system card | |
| CN109350661B (en) | Fermented traditional Chinese medicine composition for relieving cough and reducing sputum and application thereof in preventing and treating porcine respiratory diseases | |
| CN113181229B (en) | Application of cabbage type rape-isatis tinctoria G monomer addition system in inhibiting novel coronavirus SARS-CoV-2 | |
| CN113813306B (en) | Traditional Chinese medicine composition for preventing and treating infectious rhinitis of chicken | |
| CN115721677B (en) | Traditional Chinese medicine composition for preventing and treating calf bacterial diarrhea, and preparation method and application thereof | |
| CN114224989B (en) | Traditional Chinese medicine composition for resisting helicobacter pylori | |
| CN108926585A (en) | Application of the wintersweet genus plants extract in pharmacy | |
| CN107252454B (en) | Application of medicine composition containing black tea extract in treating sepsis | |
| CN1785392A (en) | Chinese medicinal composition for treating prostatitis and its preparation method |
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 | ||
| ASS | Succession or assignment of patent right |
Owner name: ZHEJIANG ZHONGYI PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: WANG ZIHOU Effective date: 20140214 |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 100050 XICHENG, BEIJING TO: 323000 LISHUI, ZHEJIANG PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20140214 Address after: No. 279 road 323000 Zhejiang Green Valley City of Lishui province Shuige Industrial Zone Patentee after: ZHEJIANG ZHONGYI PHARMACEUTICAL Co.,Ltd. Address before: 100050 Beijing city Xicheng District South Road No. two building No. nine hospital three gate 603. Patentee before: Wang Zihou |
|
| TR01 | Transfer of patent right | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: No. 279 road 323000 Zhejiang Green Valley City of Lishui province Shuige Industrial Zone Patentee after: Zhejiang Zhongyi Pharmaceutical Co.,Ltd. Address before: No. 279 road 323000 Zhejiang Green Valley City of Lishui province Shuige Industrial Zone Patentee before: ZHEJIANG ZHONGYI PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20151106 Address after: 321000 Zhejiang province Jinhua Bada big industrial zone Mount Huangshan Road No. 328 Patentee after: Zhejiang public health pharmaceutical Co.,Ltd. Address before: No. 279 road 323000 Zhejiang Green Valley City of Lishui province Shuige Industrial Zone Patentee before: Zhejiang Zhongyi Pharmaceutical Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221011 Address after: 1107/F, Building 5, Anhuili Second District, Chaoyang District, Beijing 100020 Patentee after: Zhou Yicheng Address before: 321000 no.328, Bada Road, Dahuangshan Industrial Zone, Jinhua City, Zhejiang Province Patentee before: Zhejiang public health pharmaceutical Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230511 Address after: 321000 no.328, Bada Road, Dahuangshan Industrial Zone, Jinhua City, Zhejiang Province Patentee after: Zhejiang public health pharmaceutical Co.,Ltd. Address before: 1107/F, Building 5, Anhuili Second District, Chaoyang District, Beijing 100020 Patentee before: Zhou Yicheng |