CN108653574B - 益生菌发酵的抗病毒组合物及其制备方法和应用 - Google Patents
益生菌发酵的抗病毒组合物及其制备方法和应用 Download PDFInfo
- Publication number
- CN108653574B CN108653574B CN201810915560.8A CN201810915560A CN108653574B CN 108653574 B CN108653574 B CN 108653574B CN 201810915560 A CN201810915560 A CN 201810915560A CN 108653574 B CN108653574 B CN 108653574B
- Authority
- CN
- China
- Prior art keywords
- composition
- chinese medicine
- traditional chinese
- preparation
- lactobacillus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 51
- 239000006041 probiotic Substances 0.000 title claims abstract description 31
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 31
- 230000000840 anti-viral effect Effects 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 76
- 238000000855 fermentation Methods 0.000 claims abstract description 25
- 230000004151 fermentation Effects 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 241000205585 Aquilegia canadensis Species 0.000 claims abstract description 10
- 240000000691 Houttuynia cordata Species 0.000 claims abstract description 10
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims abstract description 10
- 229910017053 inorganic salt Inorganic materials 0.000 claims abstract description 10
- 244000303040 Glycyrrhiza glabra Species 0.000 claims abstract description 9
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims abstract description 9
- 235000013719 Houttuynia cordata Nutrition 0.000 claims abstract description 9
- 235000011477 liquorice Nutrition 0.000 claims abstract description 9
- 238000002791 soaking Methods 0.000 claims abstract description 8
- 235000004347 Perilla Nutrition 0.000 claims abstract description 7
- 244000124853 Perilla frutescens Species 0.000 claims abstract description 7
- 241000131458 Elsholtzia Species 0.000 claims abstract description 6
- 244000111489 Gardenia augusta Species 0.000 claims abstract description 6
- 244000274050 Platycodon grandiflorum Species 0.000 claims abstract description 6
- 235000006753 Platycodon grandiflorum Nutrition 0.000 claims abstract description 6
- 244000197580 Poria cocos Species 0.000 claims abstract description 6
- 235000008599 Poria cocos Nutrition 0.000 claims abstract description 6
- 244000234609 Portulaca oleracea Species 0.000 claims abstract description 6
- 235000001855 Portulaca oleracea Nutrition 0.000 claims abstract description 6
- 235000005187 Taraxacum officinale ssp. officinale Nutrition 0.000 claims abstract description 6
- 240000001949 Taraxacum officinale Species 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 14
- 230000001580 bacterial effect Effects 0.000 claims description 14
- 241000894006 Bacteria Species 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 8
- 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 claims description 7
- 239000007836 KH2PO4 Substances 0.000 claims description 7
- 244000057717 Streptococcus lactis Species 0.000 claims description 7
- 235000014897 Streptococcus lactis Nutrition 0.000 claims description 7
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 7
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 239000008103 glucose Substances 0.000 claims description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 7
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 claims description 7
- 230000001954 sterilising effect Effects 0.000 claims description 7
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 7
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 7
- 239000011686 zinc sulphate Substances 0.000 claims description 7
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 6
- 229930006000 Sucrose Natural products 0.000 claims description 6
- 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 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 230000000087 stabilizing effect Effects 0.000 claims description 6
- 240000001046 Lactobacillus acidophilus Species 0.000 claims description 5
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 claims description 5
- 241000186604 Lactobacillus reuteri Species 0.000 claims description 5
- 239000004376 Sucralose Substances 0.000 claims description 5
- 238000012258 culturing Methods 0.000 claims description 5
- 229940039695 lactobacillus acidophilus Drugs 0.000 claims description 5
- 229940001882 lactobacillus reuteri Drugs 0.000 claims description 5
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 5
- 235000019408 sucralose Nutrition 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- 241000186012 Bifidobacterium breve Species 0.000 claims description 4
- 240000006024 Lactobacillus plantarum Species 0.000 claims description 4
- 235000013965 Lactobacillus plantarum Nutrition 0.000 claims description 4
- 229940072205 lactobacillus plantarum Drugs 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 2
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 2
- 238000004806 packaging method and process Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 33
- 238000012360 testing method Methods 0.000 abstract description 18
- 238000000338 in vitro Methods 0.000 abstract description 10
- 241000725643 Respiratory syncytial virus Species 0.000 abstract description 9
- 208000037797 influenza A Diseases 0.000 abstract description 9
- 240000005528 Arctium lappa Species 0.000 abstract description 6
- 235000003130 Arctium lappa Nutrition 0.000 abstract description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 6
- 241000334160 Isatis Species 0.000 abstract description 6
- 240000004534 Scutellaria baicalensis Species 0.000 abstract description 6
- 235000017089 Scutellaria baicalensis Nutrition 0.000 abstract description 6
- PGZUMBJQJWIWGJ-ONAKXNSWSA-N oseltamivir phosphate Chemical compound OP(O)(O)=O.CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 PGZUMBJQJWIWGJ-ONAKXNSWSA-N 0.000 abstract description 6
- 229940061367 tamiflu Drugs 0.000 abstract description 6
- 244000042430 Rhodiola rosea Species 0.000 abstract description 5
- 235000003713 Rhodiola rosea Nutrition 0.000 abstract description 5
- 241000951473 Schizonepeta Species 0.000 abstract description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052799 carbon Inorganic materials 0.000 abstract description 3
- 230000000312 effect on influenza Effects 0.000 abstract description 3
- 235000003599 food sweetener Nutrition 0.000 abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 3
- 239000003765 sweetening agent Substances 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 17
- 238000000034 method Methods 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 12
- 241000700605 Viruses Species 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 230000000968 intestinal effect Effects 0.000 description 11
- 210000003800 pharynx Anatomy 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 230000009471 action Effects 0.000 description 9
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 206010011224 Cough Diseases 0.000 description 7
- 206010013952 Dysphonia Diseases 0.000 description 7
- 208000010473 Hoarseness Diseases 0.000 description 7
- 206010028748 Nasal obstruction Diseases 0.000 description 7
- 206010039101 Rhinorrhoea Diseases 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000010753 nasal discharge Diseases 0.000 description 7
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- 241000186660 Lactobacillus Species 0.000 description 6
- 206010036790 Productive cough Diseases 0.000 description 6
- 208000003251 Pruritus Diseases 0.000 description 6
- 206010022000 influenza Diseases 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 235000008078 Arctium minus Nutrition 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000001888 Peptone Substances 0.000 description 5
- 108010080698 Peptones Proteins 0.000 description 5
- 230000000120 cytopathologic effect Effects 0.000 description 5
- 235000019319 peptone Nutrition 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 229960004793 sucrose Drugs 0.000 description 5
- 238000003809 water extraction Methods 0.000 description 5
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 4
- 241000193830 Bacillus <bacterium> Species 0.000 description 4
- 241000186000 Bifidobacterium Species 0.000 description 4
- 241000194036 Lactococcus Species 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 4
- 108010087230 Sincalide Proteins 0.000 description 4
- 241000194017 Streptococcus Species 0.000 description 4
- 241000245665 Taraxacum Species 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 238000010609 cell counting kit-8 assay Methods 0.000 description 4
- 239000012154 double-distilled water Substances 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 229940039696 lactobacillus Drugs 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 241000712461 unidentified influenza virus Species 0.000 description 4
- 210000003501 vero cell Anatomy 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 241000186605 Lactobacillus paracasei Species 0.000 description 3
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 3
- 229960000329 ribavirin Drugs 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 239000012138 yeast extract Substances 0.000 description 3
- YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 2
- 241000193749 Bacillus coagulans Species 0.000 description 2
- 241000186018 Bifidobacterium adolescentis Species 0.000 description 2
- 241001134770 Bifidobacterium animalis Species 0.000 description 2
- 241001608472 Bifidobacterium longum Species 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 206010013789 Dry throat Diseases 0.000 description 2
- 235000018958 Gardenia augusta Nutrition 0.000 description 2
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 2
- 240000002605 Lactobacillus helveticus Species 0.000 description 2
- 235000013967 Lactobacillus helveticus Nutrition 0.000 description 2
- 241000186869 Lactobacillus salivarius Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000194020 Streptococcus thermophilus Species 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940054340 bacillus coagulans Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940118852 bifidobacterium animalis Drugs 0.000 description 2
- 229940009291 bifidobacterium longum Drugs 0.000 description 2
- WUADCCWRTIWANL-UHFFFAOYSA-N biochanin A Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O WUADCCWRTIWANL-UHFFFAOYSA-N 0.000 description 2
- 238000003570 cell viability assay Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229960003720 enoxolone Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 229940054346 lactobacillus helveticus Drugs 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 238000009629 microbiological culture Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- 241000213006 Angelica dahurica Species 0.000 description 1
- 235000001405 Artemisia annua Nutrition 0.000 description 1
- 240000000011 Artemisia annua Species 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241000196131 Dryopteris filix-mas Species 0.000 description 1
- 231100000491 EC50 Toxicity 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 235000013717 Houttuynia Nutrition 0.000 description 1
- 235000013958 Lactobacillus casei Nutrition 0.000 description 1
- 241000218492 Lactobacillus crispatus Species 0.000 description 1
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 1
- 241000186840 Lactobacillus fermentum Species 0.000 description 1
- 241001468157 Lactobacillus johnsonii Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 241000219784 Sophora Species 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 238000002832 anti-viral assay Methods 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 229940002008 bifidobacterium bifidum Drugs 0.000 description 1
- 229940004120 bifidobacterium infantis Drugs 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- 229940045109 genistein Drugs 0.000 description 1
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002443 hepatoprotective effect Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 150000002515 isoflavone derivatives Chemical class 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 229930013032 isoflavonoid Natural products 0.000 description 1
- 150000003817 isoflavonoid derivatives Chemical class 0.000 description 1
- 235000012891 isoflavonoids Nutrition 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 230000009916 joint effect Effects 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 229940017800 lactobacillus casei Drugs 0.000 description 1
- 229940012969 lactobacillus fermentum Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 150000003243 quercetin Chemical class 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000003385 ring cleavage reaction Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000000576 supplementary effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
- A61K36/355—Lonicera (honeysuckle)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/19—Acanthaceae (Acanthus family)
- A61K36/195—Strobilanthes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/233—Bupleurum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/288—Taraxacum (dandelion)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
- A61K36/315—Isatis, e.g. Dyer's woad
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/34—Campanulaceae (Bellflower family)
- A61K36/346—Platycodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/41—Crassulaceae (Stonecrop family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/535—Perilla (beefsteak plant)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/538—Schizonepeta
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/539—Scutellaria (skullcap)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
- A61K36/634—Forsythia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/744—Gardenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/78—Saururaceae (Lizard's-tail family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8969—Polygonatum (Solomon's seal)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Botany (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明公开了一种益生菌发酵的抗病毒组合物及其制备方法和应用,所述组合物由金银花、鱼腥草、陈皮、甘草、柴胡、黄芩、板蓝根、牛蒡子、红景天、荆芥、连翘、茯苓、蒲公英、紫苏叶、香薷、黄精、马齿苋、栀子、桔梗加水浸泡、煎煮、浓缩后,添加或不添加碳源、氮源、无机盐、甜味剂,经益生菌发酵制得。经试验证明,本发明的益生菌发酵组合物体外对呼吸道合胞病毒(RSV)Long株、甲型H1N1流感病毒FM1株、H1N1达菲耐药株均有显著的抑制作用;经临床证明,本发明的发酵组合物对甲型H1N1流感有显著疗效,并且患者易于接受。
Description
技术领域
本发明涉及一种经益生菌发酵的抗病毒组合物及其制备方法和应用,特别涉及用于预防和治疗病毒性感冒的组合物及其制备方法和应用,属于医药技术领域。
背景技术
病毒性感冒是呼吸道最常见的一种传染病。临床上以发热、恶寒、头痛、鼻塞、喷嚏、流涕、咽痛、咳嗽、声嘶等症状为特征。该病四季、任何年龄均可发病,通过含有病毒的飞沫、雾滴,或经污染的用具进行传播。常于机体抵抗力降低时,如受寒、劳累、淋雨等情况,原已存在或由外界侵入的病毒或/和细菌,迅速生长繁殖导致感染。因而如何能够快捷有效的治愈病毒性感冒显得尤为重要。
由于中药成分的多元化,尤其是中药复方,其抗病毒作用的发挥是多组分共同作用而产生的, 因此其抗病毒机制是多种途径综合作用的结果。主要通过直接和间接两种途径发挥抗病毒作用。直接抗病毒是侵入前阻止吸附和细胞内抑制增殖;间接抗病毒是对机体免疫系统的调节影响。中药及复方抗病毒药物具有来源广泛、减少耐药性、毒副作用低、增强机体免疫功能等优势。例如:申请号 200910210723.3公开了一种预防和治疗H1N1 病毒性感冒的中药组合物及其制备方法。主要由板蓝根、忍冬藤、山豆根、重楼、鱼腥草、绵马贯众、青蒿、白芷组成,采用水提醇沉工艺制备而成。申请号 201210157867.9公开了一种治疗病毒性感冒的中药组合物及其制备方法,主要由防风、紫菀、桑白皮、黄芩、紫苏子、百部、陈皮、甘草组成。采用水提醇沉工艺,配以辅料和矫味剂,经过常规工序直接或间接制成药剂学上可接受的制剂。申请号201310010964.X公开了一种治疗感冒的药物组合物及其制备方法和用途,主要采用紫苏叶、黄芩、牛蒡子等原料,采用水提、醇提、挥发油用β- 环糊精包合工艺制备的制剂。
中药治病的物质基础是其所含有的化学物质,这些化学物质经口进入人体之后,可表现有不同的运转途径:(1)原型化合物被机体吸收并进入循环发挥其药理作用;(2)原型化合物被机体吸收,经肝肠循环或在组织或血液内经过一系列代谢加工后发挥其药理作用;(3)化合物不被吸收,只能随粪便排出体外;(4)药物或其原型化合物在肠道正常菌群的作用下发生某些由肠道细菌代谢酶导致的化学改变,改善了其吸收率、运转速度及生物学活性,从而在降低毒副作用的同时更有利于其药理学功能的发挥。
现有技术均采用普通水提或醇提或水提醇沉工艺制备而成,其缺点是提取物均为中药原型成分或者“天然前体药物”,均没有考虑肠道菌群对药物吸收的影响,患者食欲减退,肠道菌群失调,使得药物吸收减弱,甚至无法吸收。肖娟等(中国实验方剂学杂志,2012,18(5):247)报道,许多中药成分都是借助肠道细菌的作用转化为有效成分而达到治疗作用,尤其是具有水溶性糖部分的葡萄糖苷成分。这类化合物通常在肠道内难以吸收,生物利用度低。其原形物药理活性较小,经肠菌代谢后被水解生成苷元而发挥其药理作用。
自十九世纪五十年代以来,已有许多研究者利用不同的动物模型和方法,研究了肠道正常菌群对天然药物或其有效成分的转化及结构修饰。许多体内和体外研究证明,肠道正常菌群对天然化合物存在一个生物转化和结构修饰的复杂代谢加工过程,从而对天然中草药的体内吸收、运输、代谢及作用的发挥起着重要作用。例如,Dooth等人(Dooth AN etal..,J.Biol.Chem.,223:251,1956)的早期研究发现,给小鼠经口灌服槲皮素后,尿中可检出3,4—二羟基苯乙酸等B环裂解产物,但预先给动物投用抗生素(如新霉素),尿中则不能检出这些槲皮素代谢产物。结果提示这些裂解产物是经肠内细菌代谢转化而产生的。小桥恭一等人(和成医药学杂志,15(1):1-13,1998)使用限菌大鼠和无菌大鼠模型进行的实验进一步证明,口服投用的甘草甜素只有在肠道内被细菌酶水解成甘草次酸后才能通过肠粘膜细胞被吸收(血浆内甘草次酸水平升高),并进而在体内发挥其保肝作用(导致血清AST和ACT转氨酶降低)。另外,还有的实验观察到,将羊的肠内容物与豆科植物来源的异黄酮类化合物一起保温,可导致这些化合物的结构改变,即可使7—羟基—4—甲基异黄酮转化成大豆糖苷配基和epuol,同时使鹰嘴豆芽素A转化成染料木黄酮。表明羊肠道内容物中的肠道菌群具有生物转化异黄酮类化合物的能力(Niissou,A,etal.,Biochem. Biophys.Acta,148:92,1967)。
上述这些及其他许多实验均提示,已知结构或未知结构的天然药物,如通过胃肠道途径摄入体内后,必须经过肠道内菌群或其代谢产物的作用,并发生某些结构改变后才能被吸收并发挥其生物学活性。
发明内容
为了克服现有技术的缺陷,申请人在长期实践中,利用多种益生菌与多种中药组合物的水提取物一起进行体外发酵,结果令人惊喜地发现,某些中药组合物经益生菌发酵处理后,显著地提高了生物学活性。
本发明的一个目的是提供一种益生菌发酵的抗病毒组合物,所述的组合物包括中药复方成分、益生菌菌体、益生菌代谢产物。该组合物是中药复方提取物经益生菌发酵处理后所得到的发酵产物。本发明中,由抗病毒中药复方提取物经益生菌发酵处理后所得到的发酵产物被简称为发酵组合物。
本发明的技术方案如下:
所述中药复方的成分及含量为:每1000mL抗病毒组合物中含:金银花20~80g、鱼腥草20~80g、陈皮10~48g、甘草5~20g、柴胡0~120g、黄芩0~40g、板蓝根0~160g、牛蒡子0~40g、红景天0~40g、荆芥0~40g、连翘0~80g、茯苓0~50g、蒲公英0~36g、紫苏叶0~30g、香薷0~40g、黄精0~48g、马齿苋0~48g、栀子0~48g、桔梗0~32g;所述的组合物由上述中药复方加水浸泡、煎煮、浓缩后,添加或不添加碳源、氮源、无机盐、甜味剂,经益生菌发酵制得。
所述的益生菌选自链球菌属、乳球菌属、芽孢杆菌属、双歧杆菌属和乳杆菌属。
优选的,所述中药复方的成分及含量为:每1000mL抗病毒组合物中含:金银花20g、鱼腥草20g、茯苓30g、蒲公英20g、紫苏叶15g、香薷20g、马齿苋20g、黄精20g、陈皮20g、栀子15g、桔梗15g、甘草5g;
优选的,所述中药复方的成分及含量为:每1000mL抗病毒组合物中含:柴胡60g、金银花60g、鱼腥草60g、黄芩20g、连翘60g、板蓝根100g、牛蒡子20g、红景天20g、荆芥20g、陈皮20g、甘草20g。
所述的碳源及添加量为:重量g/体积mL百分比为0.5~1.5%的葡萄糖。
所述的氮源及添加量为:重量g/体积mL百分比为0~0.2%的酵母粉、重量g/体积mL百分比为0~0.4%的酵母膏、重量g/体积mL百分比为0~0.5%的蛋白胨。
所述的无机盐及添加量为:FeSO4•7H2O 5.0mg/100mL、ZnSO4•7H2O 4.4mg/100mL、MgSO4•7H2O 30mg/100mL、KH2PO4 100mg/100mL、K2HPO4•3H2O 100mg/100mL。
所述的甜味剂及添加量为:重量g/体积mL百分比为0~10%的蔗糖、重量g/体积mL百分比为0~0.03%的三氯蔗糖。
本发明的另一个目的是提供所述的益生菌发酵的抗病毒组合物的制备方法,包括以下步骤:
a. 取中药复方中的味药,加水浸泡、煎煮0.5~2.0 小时,取煎液,药渣第二次再加水煎煮0.5~2.0 小时,合并煎液,滤过,滤液减压浓缩至60℃下测定相对密度为1.01 ~1.10;
b.上述浓缩液加入重量g/体积mL百分比为0.5~1.5%的葡萄糖、重量g/体积mL百分比为0~0.2%的酵母粉、重量g/体积mL百分比为0~0.4%的酵母膏、重量g/体积mL百分比为0~0.5%的蛋白胨、无机盐(FeSO4•7H2O 5.0mg/100ml、ZnSO4•7H2O 4.4mg/100ml、MgSO4•7H2O 30mg/100ml、KH2PO4 100mg/100ml、K2HPO4•3H2O 100mg/100ml)、重量g/体积mL百分比为0~10%的蔗糖、重量g/体积mL百分比为0~0.03%的三氯蔗糖,调整pH值7.0±0.5,定容至规定体积,并于110~121℃下灭菌30~60分钟,温度降至28~40℃时,接种预培养的体积百分比各为0.2~1.0%的一种或者两种双歧杆菌的菌液、体积百分比为0~1.0%的链球菌的菌液、体积百分比为0~1.0%的芽孢杆菌的菌液,常规培养2~12小时,再接种预培养的体积百分比各为0.2~1.0%的两种或者三种乳杆菌的菌液和体积百分比0~1.0%的一种乳球菌的菌液,然后继续发酵12~48小时,当pH降至4.1以下时结束发酵;
c.稳定化处理,无菌分装,即得所述的益生菌发酵的抗病毒组合物;
所述的链球菌选自嗜热链球菌;所述的乳球菌选自乳酸乳球菌乳亚种、乳酸乳球菌乳脂亚种、乳酸乳球菌双乙酰亚种;所述的芽孢杆菌选自凝结芽孢杆菌;所述的双歧杆菌选自两歧双歧杆菌、短双歧杆菌、长双歧杆菌、动物双歧杆菌、青春双歧杆菌和婴儿双歧杆菌;所述的乳杆菌选自罗伊氏杆菌、嗜酸乳杆菌、德氏乳杆菌、植物乳杆菌、卷曲乳杆菌、瑞士乳杆菌、唾液乳杆菌、格式乳杆菌、约氏乳杆菌、副干酪乳杆菌、发酵乳杆菌、干酪乳杆菌和鼠李糖乳杆菌。
制备方法步骤b中所述的接种的方式也可为同时接种预培养的体积百分比各0.2~1.0%的一种或者两种双歧杆菌的菌液、体积百分比0~1.0%的链球菌的菌液、体积百分比0~1.0%的一种乳球菌的菌液、体积百分比0~1.0%的芽孢杆菌的菌液和体积百分比各0.2~1.0%的两种或者三种乳杆菌的菌液;所述发酵的时间为常规发酵14~60小时,当pH降至4.1以下时结束发酵。
上述菌种来源于中国科学院微生物研究所(AS)或中国典型培养物保藏中心(CCTCC)(中国,武汉)或中国普通微生物菌种保藏管理中心(CGMCC)(中国,北京)或中国工业微生物菌种保藏管理中心(CICC)或者从正常人的粪便或肠粘膜组织中分离得到这些细菌菌株。
益生菌是含有生理活性的微生物,当被机体经过口服摄入适当数量后,能够改善机体正常的微生物菌群平衡,以及能够刺激机体特异性、非特异性免疫机制,最终提高机体健康水平和健康状态。
本发明利用对人体有益的细菌,在体外发酵中药水提物。一方面,遵守中医药理论,保留了中药的水提物全成分,保持了中药汤药的特性;另一方面,益生菌在生长繁殖过程中产生大量酶,中药提取物经过益生菌发酵,一些大分子物质在体外被转化,发生某些结构改变后,易于人体吸收,增强疗效;并且乳酸菌在发酵过程中,产生乳酸菌素,可有效抑制病原菌的生长。乳酸菌素的作用类似抗生素,但作用机制不同,乳酸菌素作用机制是先吸附在目标菌的细胞膜上、再侵入膜内而形成通透孔道,以引起胞内重要物质,如ATP、K+等流失或生化反应障碍,而导致指标菌死亡。具专一性,不产生抗药性及毒性,而且不易被小肠胰蛋白酶破坏;还有,益生菌在发酵过程中,产生丰富风味物质,改善了中药的口感。
本发明的再一个目的是提供本发明的益生菌发酵的抗病毒组合物在制备预防和治疗病毒性感冒的药物中的应用。可按照制药工业中已知的方法将本发明的发酵组合物与一种或多种医药上可接受的载体或赋形剂或稀释剂按适当的比例混合,并按已知方法除杂菌后,制成含本发明发酵组合物的各种不同剂型的制剂。
可按照已知的常规方法,将本发明的发酵组合物或上清液,添加一种或多种具有相同、相似或不同生物学活性,并对基本活性成分表现有辅助或协同作用,但彼此又互不拮抗的天然或合成的其他药物成份或其混合物,配制成适于口服给药的合剂、乳剂等。也可将本发明的发酵组合物通过适当的干燥方法,制得固体粉末,添加一种或多种具有相同、相似或不同生物学活性,并对基本活性成分表现有辅助或协同作用,但彼此又互不拮抗的天然或合成的其他药物成份或其混合物中,配制成适于口服给药的胶囊、片剂、丸剂、颗粒剂等剂型的药物。
一般说来,本发明的抗病毒组合物的口服给药剂量可根据待治疗的病症或病理状态的性质、严重程度、病人的年龄、体重、一般健康状态,以及病人对所用药物的敏感性、耐受性和给药方式等因素,按照个体化的原则由临床医生确定。
经试验证明,本发明的发酵组合物体外对呼吸道合胞病毒(RSV) Long 株、甲型H1N1流感病毒FM1 株、H1N1 达菲耐药株均有显著的抑制作用;经临床证明,本发明的发酵组合物对甲型H1N1流感有显著疗效,并且患者易于接受。
具体实施方式
实施例1:发酵组合物A的制备
按下列重量称取各中药成分:金银花20g、鱼腥草20g、茯苓30g、蒲公英20g、紫苏叶15g、香薷20g、马齿苋20g、黄精20g、陈皮20g、栀子15g、桔梗15g、甘草5g;
以上味药,加水浸泡,煎煮1.0 小时,取煎液,药渣再加水煎煮0.5 小时,合并煎液,滤过,滤液减压浓缩至950ml(60℃下测定相对密度为1.02),加入7g葡萄糖、1g酵母粉、无机盐(FeSO4•7H2O 50mg、ZnSO4•7H2O 44mg、MgSO4•7H2O 0.3g、KH2PO4 1.0g、K2HPO4•3H2O1.0g)、30g蔗糖、150mg三氯蔗糖,调整pH6.84,定容至1000ml,并于115℃下灭菌40分钟后,温度降至39℃时,接种预培养的体积百分比各0.5%的乳酸乳球菌乳亚种(CGMCC1.18)和短双歧杆菌(AS 1.2213)的菌液,37℃培养约6小时后,再接种体积百分比各0.5%的嗜酸乳杆菌(AS 1.1854)、植物乳杆菌(AS 1.19)和罗伊氏乳杆菌(CICC 6118)的菌液,37℃发酵18h,检测pH值,pH值降至4.01,结束发酵,稳定化处理,无菌分装,即得。
实施例2:发酵组合物B的制备
按下列重量称取各中药成分:柴胡60g、金银花60g、鱼腥草60g、黄芩20g、连翘60g、板蓝根100g、牛蒡子20g、红景天20g、荆芥20g、陈皮20g、甘草20g;
以上味药,加水浸泡,煎煮1.5 小时,取煎液,药渣再加水煎煮1.0 小时,合并煎液,滤过,滤液减压浓缩至60℃下测定相对密度为1.03,加入5g葡萄糖、4g蛋白胨、无机盐(FeSO4•7H2O 50mg、ZnSO4•7H2O 44mg、MgSO4•7H2O 0.3g、KH2PO4 1.0g、K2HPO4•3H2O1.0g)、200mg的三氯蔗糖,调整pH7.20,定容至1000毫升,并于121℃下灭菌30分钟后,温度降至30℃时,接种预培养的体积百分比为0.5%凝结芽孢杆菌(CICC 21735)、体积百分比为1.0%的长双歧杆菌(CICC 6212)的菌液,30℃培养12h,再接种体积百分比各0.3%的瑞士乳杆菌(CICC 22816)和副干酪乳杆菌(CICC 6236)的菌液,37℃培养48h,检测pH值,pH值降至4.08,结束发酵,稳定化处理,分装,灭菌,即得。
实施例3:发酵组合物C的制备
按下列重量称取各中药成分:金银花80g、鱼腥草80g、陈皮48g、甘草20g;
以上味药,加水浸泡,煎煮1.0 小时,取煎液,药渣再加水煎煮1.0 小时,合并煎液,滤过,滤液减压浓缩至60℃下测定相对密度为1.02,加入10g葡萄糖、2g酵母粉、2g酵母膏、5g蛋白胨、无机盐(FeSO4•7H2O 10mg、ZnSO4•7H2O 44mg、MgSO4•7H2O 0.3mg、KH2PO4 1.0g、K2HPO4•3H2O 1.0g)、100g蔗糖,调整pH7.50,加水定容至1000毫升,并于110℃下灭菌60分钟后,温度降至37℃时,同时接种预培养的体积百分比各为1.0%的动物双歧杆菌(CICC6165)、青春双歧杆菌(CICC 6176)的菌液、体积百分比各约0.5%的唾液乳杆菌(CICC23175)、罗伊氏乳杆菌(CICC 6118)和鼠李糖乳杆菌(CICC 6163)的菌液,37℃发酵60h,检测pH值,pH值降至4.02,结束发酵,稳定化处理,分装,即得。
实施例4:发酵组合物D的制备
按下列重量称取各中药成分:金银花20g、鱼腥草20g、陈皮10g、甘草5g、柴胡10g、黄芩5g、板蓝根20g、牛蒡子10g、红景天10g、荆芥10g连翘10g、茯苓20g、蒲公英6g、紫苏叶5g、香薷5g、黄精5g、马齿苋5g、栀子5g、桔梗5g;
以上味药,加水浸泡,煎煮2.0 小时,取煎液,药渣再加水煎煮2.0 小时,合并煎液,滤过,滤液减压浓缩至60℃下测定相对密度为1.02,加入15g葡萄糖、1g酵母粉、4g蛋白胨、无机盐(FeSO4•7H2O 50mg、ZnSO4•7H2O 44mg、MgSO4•7H2O 0.3g、KH2PO4 1.0g、K2HPO4•3H2O1.0g)、50g蔗糖,调整pH7.02,加水定容至1000毫升,并于115℃下灭菌40分钟后,温度降至37℃时,同时接种预培养的体积百分比各为1.0%的短双歧杆菌(AS 1.2213)、体积百分比0.5%的嗜热链球菌(AS1.1855)、体积百分比各0.5%的嗜酸乳杆菌(AS 1.1854)、植物乳杆菌(AS 1.19)和罗伊氏乳杆菌(CICC 6118)的菌液,37℃发酵40h,检测pH值,pH值降至4.04,结束发酵,稳定化处理,分装,即得。
试验例1:本发明发酵组合物与未经发酵的中药复方提取物体外抗病毒作用
本试验例旨在利用体外抗病毒实验,对本发明方法制备的发酵组合物与未经发酵的中药复方提取物进行效果对比。
取实施例1、2、3、4制备的益生菌发酵组合物A、B、C、D和按相同组方、相似方法制备的未经益生菌发酵的中药复方提取物,作为供试样品。
1、受试药对细胞的毒性测定
用CCK-8 试剂盒分别检测受试药对MDCK及Vero细胞的毒性作用。
实验步骤如下:
(1)先将悬浮细胞以3000 细胞/孔(MDCK 细胞)或1500 细胞/孔(Vero 细胞)的密度加入96 孔板,培养过夜。
(2)药物稀释:分别将各种受试药用DMEM(10%FBS,PS)10 倍稀释,用作初始浓度(1:10)。之后利用添加10%双蒸水的DMEM(10%FBS,PS)将八种受试药浓度依次倍比稀释,共准备10 个浓度梯度。添加10%双蒸水的DMEM用作阴性对照。
(3)弃去96 孔板中的培养基,分别将各稀释度的药物及阴性对照加入96 孔板中,每孔100ul。每个稀释度做3-4 个复孔。
(4)另取新的96 孔板,分别将各稀释度的药物及阴性对照加入孔中,每孔100μl。每个稀释度做2 个复孔。该组实验设为空白对照。
(5)培养48 小时后,依据CCK-8 试剂盒的说明书进行细胞活性测定,应用GraphPad Prism 5.0 软件采用非线性拟合的剂量-效应曲线,计算药物的半数细胞毒性浓度(CC50)。
测定结果见表1。
表1 各受试药对MDCK及VERO 细胞的半数毒性剂量 (CC50,mg/ml)
2、受试药体外抗病毒作用测定
病毒及细胞株
(1)病毒 呼吸道合胞病毒(RSV) Long 株、甲型H1N1 流感病毒FM1 株、H1N1 达菲耐药株,均引自中国CDC 病毒病研究所。
(2)细胞株 犬肾细胞株(MDCK)、非洲绿猴肾细胞株(Vero)均来源于山东中医药大学实验室细胞库。
实验步骤如下(以RSV 为例):
(1)将悬浮细胞以1500 细胞/孔(Vero 细胞)的密度加入96 孔板,培养过夜。
(2)药物稀释:分别将八种受试药用DMEM(10%FBS,PS)稀释,受试药的初始浓度稀释度为(1:40)(即25μl 药液+75μl 病毒准备液),之后利用添加10%双蒸水的DMEM 将八种受试药浓度依次倍比稀释,共准备8 个浓度梯度。添加10%双蒸水的DMEM 用作阴性对照。
倍比稀释的Ribavirin 用作阳性药物对照,其终浓度梯度为1000μM-15.6μM。
(3)病毒准备液:用新鲜培养基将病毒稀释到100 TCID50/75μl。用Reed-Muench公式计算病毒TCID50,本实验采用病毒滴度分别是:H1N1 的TCID50为1×10-6/ml, RSV 的TCID50 为8.14×10-7/ml,H1N1 达菲耐药株的TCID50 为5×10-6/ml。。
(4)弃去96 孔板中的培养基,每孔加入75μl 病毒准备液。之后分别将各稀释度的药物及阴性对照加入孔中,每孔25μl。每个稀释度做3-4 个复孔。预留一列孔只添加75μl新鲜培养基及25μl 阴性对照,用作正常细胞对照。最终八种受试药稀释梯度为1:40-1:5120,同时平行设置病毒毒性对照及空白对照。
(5)培养48 小时后,观察每孔CPE 程度,并依据CCK-8 试剂盒的说明书进行细胞活性测定。每孔全部细胞病变或75%以上细胞病变记为++++,50%-75%细胞病变记为+++,25%-50%细胞病变记为++,少于25%细胞病变记为+,无明显细胞病变记为-。应用GraphPadPrism 5.0 软件采用非线性拟合的剂量-效应曲线,计算药物抗病毒的半数有效浓度(IC50),从而计算出药物的选择指数(SI)(SI=CC50/IC50)。
(6)说明:①对于流感病毒H1N1 ,所用培养基均为无血清培养基
+2μg/ml TPCK-trypsin+2% BSA+P/S。 ②不同病毒感染组CPE 观测及CCK-8 测定时间以不添加药物病毒感染组100%病变的时间决定,一般介于48-72 小时之间。
各受试药体外抗病毒测定结果见表2、表3和表4。
表2 各受试药抗流感病毒H1N1 的作用
实验结果表明:各受试药对流感病毒H1N1 的复制表现出明显的抑制效果,特别是经益生菌发酵的组合物样品均表现出较强抑制作用。
表3 各受试药抗流感病毒H1N1 达菲耐药株的作用
实验结果表明:各受试药对流感病毒H1N1 达菲耐药株的复制表现出明显的抑制效果,特别是经益生菌发酵的组合物样品均表现出较强抑制作用。
表4 各受试药抗RSV 的作用
实验结果表明:各受试药对RSV 的复制表现出抑制效果,特别是经益生菌发酵的组合物样品均表现出较强抑制作用。
试验例2 :本发明发酵组合物治疗甲型H1N1流行性感冒的临床观察
1.1 资料和方法
1.1.1 临床资料
本组病例均为2017 年12月至2018 年3月确诊的甲型H1N1 流行性感冒的患者,年龄1~69 岁,符合下列中西医诊断标准的患者,105例患者随机分为治疗组(发酵组合物)84例,对照组(利巴韦林)21例。治疗组84例随机分为四组(简称治疗组A、B、C、D)各21例,分别采用实施例1、2、3、4方法制备的发酵组合物A、B、C、D,各组在性别、年龄、病程和病情分布上无统计学意义(P>0.05)。
1.1.2 诊断标准
1.1.2.1 西医诊断标准
(1)临床症状:有肯定的流感病毒甲型H1N1 感染病史,急性起病,病程≤ 2 天;伴有咳嗽、咳痰、流涕、鼻塞、咽痒、咽干痛、声音嘶哑等症状;
(2)体检:咽部充血,扁桃体肿大,两肺呼吸音稍粗糙或不粗糙;
(3)血清学检查:采用RT-PCR 法检测流感病毒甲型H1N1 阳性,外周血常规白细胞计算及分类均在正常范围之间或白细胞计数低下;
(4)X线胸片检查基本正常。
1.1.2.2 中医诊断标准:
临床上以咳嗽、咳痰、流涕、鼻塞、咽痒、咽干痛、声音嘶哑等症状为主要特征,舌略红、苔薄黄、脉浮数。
1.2 治疗方法
治疗组给予本发明发酵的抗病毒组合物,口服,每日两次,每次用量100ml;对照组用利巴韦林泡腾颗粒150mg/ 次,每日3 次,口服。儿童酌减。疗程为5 天。
1.3 疗效标准
疗效标准:
痊愈:治疗五天内咳嗽、咳痰、流涕、鼻塞、咽痒、咽干痛、声音嘶哑等临床症状体征消失;
显效:治疗五天内咳嗽、咳痰、流涕、鼻塞、咽痒、咽干痛、声音嘶哑等临床症状体征减轻2/3 以上;
有效:治疗五天内咳嗽、咳痰、流涕、鼻塞、咽痒、咽干痛、声音嘶哑等临床症状体征减轻2/3 ~ 1/3 ;
无效:治疗五天内自觉或其他症状均无明显改善或加重。
1.4 结果:见表5。
表5治疗甲型H1N1 流行性感冒临床结果
运用本发明实施例1、2、3、4 的发酵组合物(治疗组A、B、C、D)治疗甲型H1N1 流行性感冒,结果表明:治疗组患者用药后咳嗽、咳痰、流涕、鼻塞、咽痒、咽干痛、声音嘶哑等临床症状改善,治疗组A、B、C、D 临床改善总有效率分别为90.48%、85.71%、80.95%、71.42% ;对照组临床改善总有效率为38.09% ;各治疗组与对照组比较差异有统计学意义(P <0.05)。在临床治疗观察中未发现毒副作用。临床结果提示:本发明实施例1、2 、3、4制备的发酵组合物治疗甲型H1N1 流行性感冒疗效满意,在缓解临床症状时间及总有效率及治愈率方面发酵组合物组均优于利巴韦林组。
Claims (2)
1.一种益生菌发酵的抗病毒组合物,其特征在于,所述组合物由中药复方成分和益生菌菌体通过发酵制成:
所述中药复方按下列重量称取各中药成分:金银花20g、鱼腥草20g、茯苓30g、蒲公英20g、紫苏叶15g、香薷20g、马齿苋20g、黄精20g、陈皮20g、栀子15g、桔梗15g、甘草5g;其制备方法步骤如下:
以上味药,加水浸泡,煎煮1.0 小时,取煎液,药渣再加水煎煮0.5 小时,合并煎液,滤过,滤液减压浓缩至950ml,60℃下测定相对密度为1.02;加入7g葡萄糖、1g酵母粉、无机盐、30g蔗糖、150mg三氯蔗糖,调整pH6.84,定容至1000ml;于115℃下灭菌40分钟后,温度降至39℃时,接种预培养的体积百分比各0.5%的乳酸乳球菌乳亚种和短双歧杆菌的菌液,37℃培养6小时后,再接种体积百分比各0.5%的嗜酸乳杆菌、植物乳杆菌和罗伊氏乳杆菌的菌液,37℃发酵18h,检测pH值,pH值降至4.01,结束发酵,稳定化处理,无菌分装,即得;
所述无机盐为:FeSO4•7H2O 50mg、ZnSO4•7H2O 44mg、MgSO4•7H2O 0.3g、KH2PO4 1.0g、K2HPO4•3H2O 1.0g。
2.权利要求1所述的益生菌发酵的抗病毒组合物在制备预防和治疗病毒性感冒的药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810915560.8A CN108653574B (zh) | 2018-08-13 | 2018-08-13 | 益生菌发酵的抗病毒组合物及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810915560.8A CN108653574B (zh) | 2018-08-13 | 2018-08-13 | 益生菌发酵的抗病毒组合物及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108653574A CN108653574A (zh) | 2018-10-16 |
CN108653574B true CN108653574B (zh) | 2021-07-20 |
Family
ID=63788373
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810915560.8A Active CN108653574B (zh) | 2018-08-13 | 2018-08-13 | 益生菌发酵的抗病毒组合物及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108653574B (zh) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109576185B (zh) | 2018-12-26 | 2020-07-03 | 江南大学 | 一种具有抗流感能力的益生菌混合制剂及其应用 |
CN110960623A (zh) * | 2019-12-31 | 2020-04-07 | 山西大禹生物工程股份有限公司 | 家禽用抗病毒发酵中药及其制备方法 |
TWI805237B (zh) * | 2020-05-06 | 2023-06-11 | 葡萄王生技股份有限公司 | 乳酸菌用於製備抗病毒組合物的用途 |
CN116549347A (zh) * | 2022-01-28 | 2023-08-08 | 北京工商大学 | 一种连翘果发酵物及其制备方法及应用 |
CN114681530B (zh) * | 2022-03-22 | 2023-08-01 | 石家庄以岭药业股份有限公司 | 中药组合物或其发酵产物的应用、动物饲料及动物饲料添加剂 |
CN117100833B (zh) * | 2023-10-07 | 2024-06-07 | 青苗医疗有限公司 | 一种调理肠道菌群的中药组合物及其制备方法和应用 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1293960A (zh) * | 2000-09-26 | 2001-05-09 | 陈昌陶 | 复方抗病毒药物 |
CN1739748A (zh) * | 2005-09-14 | 2006-03-01 | 广州福寿仙药业有限公司 | 一种感冒治疗药物及其制备方法 |
CN1772276A (zh) * | 2005-10-26 | 2006-05-17 | 牟培新 | 一种治疗流感的药物 |
CN101940653A (zh) * | 2010-09-04 | 2011-01-12 | 荣成市科学技术情报研究所 | 一种治疗病毒感冒的中药 |
CN102114197A (zh) * | 2010-05-13 | 2011-07-06 | 于进香 | 一种治疗流行性感冒的中药口服汤剂 |
CN103223020A (zh) * | 2013-05-21 | 2013-07-31 | 卫斌 | 一种治疗病毒性感冒的药物及其制备方法 |
CN103933128A (zh) * | 2014-04-30 | 2014-07-23 | 青岛农业大学 | 一种清热解毒的药物组合物及其制备方法 |
CN105770525A (zh) * | 2016-03-11 | 2016-07-20 | 三株福尔制药有限公司 | 一种益生菌发酵药食两用中药组合物及其制备方法和应用 |
CN106551378A (zh) * | 2015-09-16 | 2017-04-05 | 三株福尔制药有限公司 | 一种益生菌发酵蛹虫草的组合物及其制备方法和应用 |
CN107019739A (zh) * | 2016-08-30 | 2017-08-08 | 河南牧翔动物药业有限公司 | 一种鱼腥草芩蓝口服液及其制备方法和产品质量控制方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1192783C (zh) * | 2000-01-01 | 2005-03-16 | 同济医科大学附属同济医院 | 一种清热解毒抗感染中药的制备方法 |
CN107616277B (zh) * | 2017-10-27 | 2020-11-03 | 力致(厦门)生物科技有限公司 | 一种呼吸道保健茶及其制备方法和应用 |
-
2018
- 2018-08-13 CN CN201810915560.8A patent/CN108653574B/zh active Active
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1293960A (zh) * | 2000-09-26 | 2001-05-09 | 陈昌陶 | 复方抗病毒药物 |
CN1739748A (zh) * | 2005-09-14 | 2006-03-01 | 广州福寿仙药业有限公司 | 一种感冒治疗药物及其制备方法 |
CN1772276A (zh) * | 2005-10-26 | 2006-05-17 | 牟培新 | 一种治疗流感的药物 |
CN102114197A (zh) * | 2010-05-13 | 2011-07-06 | 于进香 | 一种治疗流行性感冒的中药口服汤剂 |
CN101940653A (zh) * | 2010-09-04 | 2011-01-12 | 荣成市科学技术情报研究所 | 一种治疗病毒感冒的中药 |
CN103223020A (zh) * | 2013-05-21 | 2013-07-31 | 卫斌 | 一种治疗病毒性感冒的药物及其制备方法 |
CN103933128A (zh) * | 2014-04-30 | 2014-07-23 | 青岛农业大学 | 一种清热解毒的药物组合物及其制备方法 |
CN106551378A (zh) * | 2015-09-16 | 2017-04-05 | 三株福尔制药有限公司 | 一种益生菌发酵蛹虫草的组合物及其制备方法和应用 |
CN105770525A (zh) * | 2016-03-11 | 2016-07-20 | 三株福尔制药有限公司 | 一种益生菌发酵药食两用中药组合物及其制备方法和应用 |
CN107019739A (zh) * | 2016-08-30 | 2017-08-08 | 河南牧翔动物药业有限公司 | 一种鱼腥草芩蓝口服液及其制备方法和产品质量控制方法 |
Non-Patent Citations (3)
Title |
---|
清解退热汤为主治疗小儿急性上呼吸道感染80例;耿少怡等;《河南中医》;20050710(第07期);第64-65页 * |
病毒清颗粒剂的制备及临床应用;郑修丽等;《中国医院药学杂志》;20030928(第09期);第568-569页 * |
自拟双防解毒汤防治急性呼吸道病毒感染性疾病的体会;陈玉明等;《内蒙古中医药》;20070120(第01期);第17页左栏第2-3段 * |
Also Published As
Publication number | Publication date |
---|---|
CN108653574A (zh) | 2018-10-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108653574B (zh) | 益生菌发酵的抗病毒组合物及其制备方法和应用 | |
JP5340302B2 (ja) | キグシを含む加味雙和湯を有効成分として含有する二日酔い解消用組成物 | |
CN103908585B (zh) | 用于预防和治疗便秘的益生菌发酵组合物 | |
KR101104397B1 (ko) | 유산균 발효유 필터액을 함유하는 바이러스 감염 질환 예방또는 치료용 조성물 | |
CN117487683A (zh) | 具有抗幽护胃和消食化积功效的益生菌组合物及其应用 | |
JP2004505625A (ja) | 腸内共生生物の共発酵培養による天然薬の転換および修飾 | |
CN105878554A (zh) | 一种益生菌发酵八珍汤组合物及其制备方法和应用 | |
CN103446552B (zh) | 用于预防和治疗消化系统疾病的发酵组合物 | |
CN112007106B (zh) | 一种提高免疫力的发酵组合物及其制备方法 | |
CN112569323A (zh) | 一种解酒护肝的组合物及其应用 | |
CN105748622A (zh) | 一种用于解痉镇痛的益生菌发酵中药组合物及其制备方法和应用 | |
CN103585433A (zh) | 一种治疗口腔溃疡的中药组合物 | |
CN114869917B (zh) | 植物乳杆菌n13在制备防治阴道炎或抑制病原菌药物中的用途 | |
CN117224635A (zh) | 一种复合益生菌发酵中药复方组合物及其制备方法和应用 | |
CN114452308B (zh) | 一种益生菌保护剂及其制备的微生态制剂和用途 | |
KR100988923B1 (ko) | 쌍화탕 유산균 발효물을 포함하는 숙취해소용 조성물 | |
CN105535743A (zh) | 一种益生菌发酵型宣肺止咳合剂及其制备方法 | |
CN105770525A (zh) | 一种益生菌发酵药食两用中药组合物及其制备方法和应用 | |
KR20110068889A (ko) | 한약재 발효물을 유효성분으로 포함한 비만 또는 고지혈증의 예방 및 치료용 조성물 | |
CN113368198B (zh) | 一种治疗风热犯肺的药物组合物及其制备方法和应用 | |
TWI239244B (en) | Method for inhibiting cancer growth, reducing infection and promoting general health with a fermented soy extract | |
CN116077607B (zh) | 一种抗幽门螺杆菌感染的益生菌发酵中药组合物及其应用 | |
CN110938563A (zh) | 一种乳酸菌bj-reborn001及其在制备抑制幽门螺旋杆菌的发酵液中的应用 | |
CN108355124A (zh) | 一种治疗气道粘液高分泌的中药组合物及其应用 | |
CN113082145B (zh) | 一种提高akk菌数量的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |