CN116731891B - 一株短双歧杆菌b2798及其制备益生菌制剂的用途 - Google Patents
一株短双歧杆菌b2798及其制备益生菌制剂的用途 Download PDFInfo
- Publication number
- CN116731891B CN116731891B CN202211563484.1A CN202211563484A CN116731891B CN 116731891 B CN116731891 B CN 116731891B CN 202211563484 A CN202211563484 A CN 202211563484A CN 116731891 B CN116731891 B CN 116731891B
- Authority
- CN
- China
- Prior art keywords
- bifidobacterium breve
- probiotic
- preparation
- helicobacter pylori
- bacteria
- 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
- 241000186012 Bifidobacterium breve Species 0.000 title claims abstract description 67
- 239000006041 probiotic Substances 0.000 title claims abstract description 44
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 44
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 241000590002 Helicobacter pylori Species 0.000 claims abstract description 48
- 229940037467 helicobacter pylori Drugs 0.000 claims abstract description 48
- 241000894006 Bacteria Species 0.000 claims abstract description 38
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 19
- 239000000843 powder Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000009629 microbiological culture Methods 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 238000012545 processing Methods 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims 1
- 239000006072 paste Substances 0.000 claims 1
- 241000700159 Rattus Species 0.000 abstract description 31
- 230000000694 effects Effects 0.000 abstract description 24
- 210000001072 colon Anatomy 0.000 abstract description 13
- 230000000968 intestinal effect Effects 0.000 abstract description 13
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
- 208000024891 symptom Diseases 0.000 abstract description 8
- 230000004888 barrier function Effects 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 7
- 241001465754 Metazoa Species 0.000 abstract description 6
- 208000037816 tissue injury Diseases 0.000 abstract description 6
- 230000036039 immunity Effects 0.000 abstract description 5
- 210000004347 intestinal mucosa Anatomy 0.000 abstract description 5
- 230000037396 body weight Effects 0.000 abstract description 4
- 230000005764 inhibitory process Effects 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 3
- 238000012404 In vitro experiment Methods 0.000 abstract description 2
- 230000000813 microbial effect Effects 0.000 abstract description 2
- 230000001580 bacterial effect Effects 0.000 description 21
- 239000007787 solid Substances 0.000 description 15
- 239000002994 raw material Substances 0.000 description 13
- 239000001963 growth medium Substances 0.000 description 10
- 239000002207 metabolite Substances 0.000 description 10
- 108010046334 Urease Proteins 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 235000013361 beverage Nutrition 0.000 description 7
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 208000011231 Crohn disease Diseases 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- 239000004375 Dextrin Substances 0.000 description 3
- 229920001353 Dextrin Polymers 0.000 description 3
- 102000003777 Interleukin-1 beta Human genes 0.000 description 3
- 108090000193 Interleukin-1 beta Proteins 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 208000008469 Peptic Ulcer Diseases 0.000 description 3
- 229920001100 Polydextrose Polymers 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 235000019425 dextrin Nutrition 0.000 description 3
- 235000013399 edible fruits Nutrition 0.000 description 3
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 description 3
- 229940107187 fructooligosaccharide Drugs 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 229940088592 immunologic factor Drugs 0.000 description 3
- 239000000367 immunologic factor Substances 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000000832 lactitol Substances 0.000 description 3
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 3
- 229960003451 lactitol Drugs 0.000 description 3
- 235000010448 lactitol Nutrition 0.000 description 3
- 238000009630 liquid culture Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000001259 polydextrose Substances 0.000 description 3
- 235000013856 polydextrose Nutrition 0.000 description 3
- 229940035035 polydextrose Drugs 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- 206010019375 Helicobacter infections Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 241001052560 Thallis Species 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- -1 and the like Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000005138 cryopreservation Methods 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229920003045 dextran sodium sulfate Polymers 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 208000011906 peptic ulcer disease Diseases 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- AANMVENRNJYEMK-UHFFFAOYSA-N 4-propan-2-ylcyclohex-2-en-1-one Chemical compound CC(C)C1CCC(=O)C=C1 AANMVENRNJYEMK-UHFFFAOYSA-N 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000036649 Dysbacteriosis Diseases 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 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
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010051606 Necrotising colitis Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010227 cup method (microbiological evaluation) Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000008394 flocculating agent Substances 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000010758 granulomatous inflammation Diseases 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229940124644 immune regulator Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000007358 intestinal barrier function Effects 0.000 description 1
- 230000008944 intestinal immunity Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 1
- 229910000357 manganese(II) sulfate Inorganic materials 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 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
- 239000003607 modifier Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013406 prebiotics Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011450 sequencing therapy Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 235000019722 synbiotics Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
- 239000001393 triammonium citrate Substances 0.000 description 1
- 235000011046 triammonium citrate Nutrition 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
- A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/16—Agglomerating or granulating milk powder; Making instant milk powder; Products obtained thereby
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23F—COFFEE; TEA; THEIR SUBSTITUTES; MANUFACTURE, PREPARATION, OR INFUSION THEREOF
- A23F3/00—Tea; Tea substitutes; Preparations thereof
- A23F3/16—Tea extraction; Tea extracts; Treating tea extract; Making instant tea
- A23F3/166—Addition of, or treatment with, enzymes or microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
- A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
- A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
- A23G3/364—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
- A23G3/366—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins containing microorganisms, enzymes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L21/00—Marmalades, jams, jellies or the like; Products from apiculture; Preparation or treatment thereof
- A23L21/10—Marmalades; Jams; Jellies; Other similar fruit or vegetable compositions; Simulated fruit products
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明属于微生物益生菌剂技术领域,具体涉及一株短双歧杆菌B2798,并进一步公开其制备益生菌制剂的用途。本发明公开了一株短双歧杆菌B2798,通过动物试验证实,短双歧杆菌B2798活菌体和灭活B2798菌体均能作用于动物肠道,可有效改善肠道微生态平衡,改善机体患病症状,保护肠粘膜屏障功能,显著改善结肠组织损伤,提高大鼠体重,改善机体免疫功能,并通过体外试验证实该菌株对幽门螺旋杆菌具有一定的抑制作用。
Description
技术领域
本发明属于微生物益生菌剂技术领域,具体涉及一株短双歧杆菌B2798,并进一步公开其制备益生菌制剂的用途,特别涉及其用于制备改善肠道微生态平衡、肠道粘膜屏障、调节肠道免疫及抑制幽门螺旋杆菌制剂的用途。
背景技术
短双歧杆菌是一种革兰氏阳性菌,为无芽孢、无运动的专性厌氧细菌。短双歧杆菌具有多种形态特征,诸如短杆、分叉Y形杆、V形杆等,且在不同营养环境下存在差异,其在温度35-40℃、pH值6.5-7.0环境下最适生长。短双歧杆菌不仅能够自身合成多种营养物质,促进机体的营养合成和吸收,而且可在人体肠道菌群中起重要作用。大量动物和临床试验研究表明,短双歧杆菌在消化系统代谢方面,具有改善便秘、预防肥胖、缓解克罗恩病和改善坏死性小肠结肠炎的作用;在免疫系统调控方面,具有增强宿主免疫能力、抗过敏和减轻全身炎症反应综合征的作用,帮助患者改善临床症状,提升治疗依赖性;在神经系统调节方面,具有缓解焦虑和改善阿尔兹海默症的作用。目前,国内外对短双歧杆菌的研究已有数十年,既可作为膳食补充剂,又可作为保健食品的功能成分,应用前景广阔。
炎症性肠病(Inflammatory disease,IBD)是指原因不明的一组非特异性肠道炎症,包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD)。IBD是一种与胃肠道炎症失控有关的慢性反复发作性疾病,它已被证实容易诱发结肠直肠癌。研究表明,遗传易感个体对宿主菌群的免疫反应失调是这些疾病发展的根本原因。尽管UC和CD同属于炎症性肠病,但它们却有着各自不同的发病机理、基本炎症特性、症状和治疗策略。CD以Th1引发的炎症反应为主,其特征是以IL-12表达增加为起始,继而引起IFN和TNF-α表达增加,它可以发生在胃肠道的任何部位,其特点是透壁性肉芽肿性炎症。而UC以Th2引发的炎症反应为主,导致包括IL-5在内的促炎症细胞因子的产生增加,UC局限于结肠,通常首先累及直肠,根据疾病的严重程度不同,可以向结肠近端发展。随着近年来对IBD发病机制的深人研究,益生菌作为安全有效、无副作用的治疗剂重新激起了人们的兴趣。大量关于应用益生菌制剂治疗IBD及其并发症的实验和临床研究正在进行,单一及混合多种益生菌菌株、益生元及合生元等制剂的研究也取得了进展。
幽门螺旋杆菌(helicobacter pylori,HP)是一种可黏附定植于胃黏膜表面的微需氧革兰阴性杆菌,是胃炎、消化性溃疡的致病性因素之一,已公认在胃溃疡、十二指肠溃疡、胃癌等病症中发挥了致因作用。此外,由幽门螺旋杆菌感染引发的胃炎还被认为是消化性溃疡及其相关并发症的危险因素。因此,消除幽门螺旋杆菌不仅可显著降低发生胃癌的风险,同时还可起到预防消化性溃疡的作用,而直接或间接性的提升幽门螺旋杆菌根除率,对防治幽门螺旋杆菌及其有关疾病的发生具有重要意义。目前,传统用于根除HP的治疗方案主要为含铋剂的四联方案,而新的治疗方案如序贯疗法、左氧氟沙星疗法等,主要是通过抗生素结合的三联或者四联疗法以清除患者体内的幽门螺旋杆菌以恢复幽门螺旋杆菌感染导致的胃肠症状。但是,由于治疗过程需要联合应用多种抗生素,不仅疗程较长,且常常导致耐药、菌群失调、依从性下降等副作用,患者出现不良反应的几率极大,并降低了治疗效率。大量临床实践证实,临床上治疗幽门螺旋杆菌时结合口服肠道益生菌可起到一定的正向辅助效果。
因此,开发可辅助改善肠道免疫功能并可抑制幽门螺旋杆菌的益生菌制剂,对调节人体免疫力及改善肠道功能具有积极的意义。
发明内容
为此,本发明所要解决的技术问题在于提供一株改善肠道微生态平衡、维持肠道正常的屏障功能、免疫调节功能且在抑制幽门螺旋杆菌中具有一定作用的短双歧杆菌B2798;
本发明所要解决的第二个技术问题在于提供上述短双歧杆菌B2798及其灭活物、代谢物用于制备益生菌制剂的用途;
本发明所要解决的第三个技术问题在于提供一种幽门螺旋杆菌抑制剂。
为解决上述技术问题,本发明所述的一株短双歧杆菌B2798,其分类命名为短双歧杆菌Bifidobacterium breve,已保藏于中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为CGMCC No.22242,保藏日期为2021年4月27日,保藏地址为北京市朝阳区北辰西路1号院3号。
本发明还公开了所述的短双歧杆菌B2798及其灭活物、代谢物用于制备益生菌制剂的用途。
在本发明方案中,所述灭活物包括但不限于灭活的菌体、发酵产物、培养物等经常规灭活处理的物质,所述代谢物包括但不限于经培养、发酵、代谢、提取所得物质。
本发明还公开了一种益生菌制剂,所述益生菌制剂的活性成分包括所述的短双歧杆菌B2798的菌体、灭活物和/或代谢物。
具体的,所述益生菌制剂中,所述短双歧杆菌B2798的有效菌体数量为不少于1×106个/日。
具体的,所述益生菌制剂在液体、半固体和固体中的任何状态均可发挥健康作用。具体的,所述益生菌制剂包括散剂、颗粒剂、丸剂、胶囊剂、片剂、膏剂、液体制剂、凝胶剂、喷雾剂、固体饮料中的至少一种。
本发明还公开了一种制备所述益生菌制剂的方法,包括将所述的短双歧杆菌B2798进行菌体培养的步骤,以及按照常规工艺、添加常规辅料进行选定剂型加工的步骤。
前述“常规工艺”包括但不限于传统的工艺手段,诸如压片、分散、造粒等本领域常规的制剂手段;前述“常规辅料”包括但不限于本领域已知的辅料载体、赋形剂、佐剂、粘合剂、溶剂等种类及原料成分。
本发明所述益生菌制剂的制备方法中,短双歧杆菌B2798可经过冷冻干燥、低温喷雾干燥、喷雾干燥、带式干燥等方式获取,也可不进行任何干燥方式直接使用。
本发明还公开了所述的短双歧杆菌B2798及其灭活物、代谢物或者所述益生菌制剂用于制备具有如下(1)-(6)中至少一项功效的功能性产品的用途:
(1)可改善肠道微生态平衡;
(2)可维护肠道粘膜屏障功能;
(3)可调节肠道免疫功能;
(4)可改善肠道症状;
(5)可预防、缓解和/或治疗炎症性肠病(IBD);
(6)对幽门螺旋杆菌具有抑制作用。
本发明的一种实施方式中,所述产品中,短双歧杆菌B2798可对肠道微生态、肠道屏障、免疫调节和/或幽门螺旋杆菌均可产生有益效果,所述产生效果的模型,可以是IBD模型,但不限于IBD疾病。
具体的,所述功能性产品为药品。
本发明的一种实施方式中,所述改善肠道微生态平衡及维持肠道正常的屏障功能及免疫功能的产品,所述药品含有短双歧杆菌B2798、药物载体和/或药用辅料。
本发明的一种实施方式中,所述药用辅料包含溶剂、抛射剂、增溶剂、助溶剂、乳化剂、着色剂、黏合剂、崩解剂、填充剂、润滑剂、润湿剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗黏合剂、整合剂、渗透促进剂、pH值调节剂、缓冲剂、增塑剂、表面活性剂、发泡剂、消泡剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂以及释放阻滞剂。
本发明的一种实施方式中,所述附加剂包含微晶纤维素、羟丙基甲基纤维素以及精制卵磷脂。
本发明的一种实施方式中,所述药品的剂型包含颗粒剂、胶囊剂、片剂、丸剂或口服液。
本发明还公开了一种幽门螺旋杆菌抑制剂,所述抑制剂活性成分包括所述的短双歧杆菌B2798的菌体、灭活物和/或代谢物。
具体的,所述的幽门螺旋杆菌抑制剂中,所述短双歧杆菌B2798的有效菌体数量为不少于1×106个/日。
本发明公开了一株短双歧杆菌B2798,通过动物试验证实,短双歧杆菌B2798活菌体和灭活B2798菌体均能作用于动物肠道,可有效改善肠道微生态平衡,改善机体患病症状,保护肠粘膜屏障功能,显著改善结肠组织损伤,提高大鼠体重,改善机体免疫功能,并通过体外试验证实该菌株对幽门螺旋杆菌具有一定的抑制作用。
本发明还公开了含有所述短双歧杆菌B2798灭活菌体及其代谢物的益生菌剂,所述益生菌剂可以显著改善IBD大鼠的患病症状,显著改善IBD大鼠结肠组织损伤、提高大鼠体重,显著降低IBD大鼠血清中的IL-1β、TNF-α和IL-6含量,具有改善炎症性肠病(IBD)的作用,能通过改善肠道微生态平衡及维持肠道正常的屏障功能及免疫功能产生作用,在肠道微生态平衡、免疫调节剂以及改善肠道症状的功能性产品中具有巨大的应用前景。
本发明还公开了含有所述短双歧杆菌B2798灭活菌体及其代谢物的幽门螺旋杆菌抑制剂,所述抑制剂可以显著抑制幽门螺旋杆菌尿素酶活性能力及显著抑制幽门螺旋杆菌生长能力,具有抑制幽门螺旋杆菌的作用。所述短双歧杆菌B2798可通过抑制幽门螺旋杆菌进而达到良好的免疫功能,有效缓解炎症性肠病,在制备缓减炎症性肠病及抑制幽门螺旋杆菌的产品中具有很大的前景。
附图说明
为了使本发明的内容更容易被清楚的理解,下面根据本发明的具体实施例并结合附图,对本发明作进一步详细的说明,其中,
图1为短双歧杆菌B2798活菌体和死菌体治疗炎症性肠炎(BD)的影响实验设计流程图;
图2为不同处理组大鼠结肠H&E染色结果(×200);
图3为不同处理组大鼠体重变化结果;
图4为不同处理组大鼠组织学损伤评分结果;
图5中(a)-(c)为不同处理组对IBD大鼠免疫因子的影响结果。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述,但是本领域技术人员将会理解,下列实施例仅用于说明本发明,而不应视为限制本发明的范围。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。
本发明如下实施例及实验例中,保藏菌株--短双歧杆菌B2798,其分类命名为短双歧杆菌Bifidobacterium breve,已保藏于中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为CGMCC No.22242,保藏日期为2021年4月27日,保藏地址为北京市朝阳区北辰西路1号院3号。
本发明保藏菌株--短双歧杆菌B2798的菌体培养采用已知的培养方式即可,诸如菌体的活化及增值培养,采用已知的适宜的培养基/培养液即可,具体的培养条件参照本领域常规操作即可。
本发明如下实施例中使用的“短双歧杆菌B2798灭活菌体及其代谢物粉末”的具体获得方法包括:
将冷冻保存在-80℃的供试菌株短双歧杆菌B2798接种于改良MRS液体培养基中(121℃,15min条件下灭菌),37℃恒温厌氧条件下进行活化培养,活化完成后用移液枪将供试菌以2%的接种量接种于所述改良MRS液体培养基中,然后在37℃恒温厌氧下持续培养16-18小时,发酵至pH值4.50-4.60,经90℃、15min杀菌处理,将灭活后的发酵液进入离心机进行离心分离(转速14000rpm/min),并用无菌纯化水重复洗涤三次。再经真空冷冻干燥处理后获得所述灭活菌体及其代谢物粉末,流式细胞仪检测菌体数量高于5×1010个/g时保存备用。
所述改良MRS培养基,其成分为:细菌学蛋白胨10g/L、牛肉浸粉8g/L、酵母浸粉4g/L、葡萄糖20g/L、Tween-80 1mL、K2HPO4 2g/L、醋酸钠·3H2O 5g/L、柠檬酸三铵2g/L、MgSO4·7H20 0.2g/L、MnSO4·5H20 0.05g/L、纯化水1000mL、琼脂15g/L。所述改良MRS合成培养基购买自广东环凯微生物科技有限公司。
实施例1
本实施例为所述短双歧杆菌B2798活菌体和死菌体治疗炎症性肠病(IBD)动物试验。
本实施例结合H&E染色、体重、血清中细胞因子和组织学损伤评分综合评估B2798活菌体和死菌体对大鼠炎症性肠病的影响,具体实验方案参考附图1所示。
选择60只6周龄Wistar雄性大鼠,将其分为正常组(12只)、模型组(12只)、B2798活菌组(12只)、B2798死菌组(12只)。从第0天开始正常组灌胃2ml生理盐水,其余组灌胃2ml、3%DSS(葡聚糖硫酸钠)持续7天,从第7天开始正常组和模型组灌胃2ml生理盐水,所述短双歧杆菌B2798活菌组每只大鼠灌胃2ml含4×109活菌数的B2798活菌体、B2798死菌组每只大鼠灌胃2ml含4×109活菌数的B2798死菌体。上述操作持续三周,并在第7天、28天分别收血清样品。
1、不同处理组大鼠结肠H&E染色结果
将灌胃活B2798菌体和灭活B2798菌体的大鼠进行结肠切片,结肠H&E染色结果见附图2所示。
由图示结果显示,与模型组相比较,B2798活菌组及B2798死菌组的粘膜层肠上皮结构正常,固有层与粘膜下层的水肿较少。说明活B2798菌体和灭活B2798菌体均可显著改善IBD大鼠结肠组织损伤,改善炎症性肠病(IBD)。
2、不同处理组大鼠体重变化
将灌胃活B2798菌体和灭活B2798菌体的大鼠进行称重,结果如附图3所示。
由图示结果显示,模型组在诱导IBD大鼠后出现体重下降现象,在灌胃活B2798菌体和灭活B2798菌体后发现,与模型组相比较B2798活菌组提高大鼠体重效果不显著,而B2798死菌组可明显提高大鼠体重,说明灭活B2798菌体可有效改善炎症性肠病(IBD)。
3、不同处理组大鼠组织学损伤评分
将灌胃活B2798菌体和灭活B2798菌体的大鼠进行组织学评分,结果如附图4所示。
由图示结果显示,模型组在诱导IBD大鼠后的结肠组织损伤严重,评分明显高于正常组。在灌胃活B2798菌体和灭活B2798菌体后发现,B2798活菌组及B2798死菌组均可改善IBD大鼠结肠组织损伤,其中B2798死菌组改善IBD大鼠结肠组织损伤更加显著。说明活B2798菌体和灭活B2798菌体均可有效改善炎症性肠病(IBD)。
4、不同处理组对IBD大鼠免疫因子的影响
将灌胃活B2798菌体和灭活B2798菌体的大鼠在收集其血清后监测不同处理组对IBD大鼠免疫因子的影响,结果见附图5中(a)-(c)所示。
由图示结果显示,模型组在诱导IBD大鼠后与正常组相比IL-1β、TNF-α和IL-6含量均有所增加,在灌胃活B2798菌体和灭活B2798菌体后发现,B2798活菌组及B2798死菌组均可降低IBD大鼠血清中的IL-1β、TNF-α含量,而只有B2798死菌组能够显著降低IL-6含量。说明活B2798菌体和灭活B2798菌体可有效改善炎症性肠病(IBD)。
实施例2
本实施例为短双歧杆菌B2798活菌体抑制幽门螺旋杆菌的体外试验。
1、幽门螺旋杆菌及短双歧杆菌B2798的活化及培养
将幽门螺旋杆菌冻存管从-80℃取出后,放入37℃水浴2分钟解冻,解冻后混匀,吸取幽门螺旋杆菌菌悬液于哥伦比亚血平板上,用涂布棒将菌液均匀覆盖培养基表面,放入三气培养箱(85%N2、10%CO2、5%O2)静置培养72h。经活化两代后,将哥伦比亚血平板表面的菌落用生理盐水洗脱后制成菌悬液,备用。
将待测菌株短双歧杆菌B2798冻存管从-80℃取出后放置室温解冻,于MRS液体培养基中37℃需氧培养,菌株活化两代后制成菌悬液,备用。
按照不同比例将待测菌株短双歧杆菌B2798和幽门螺旋杆菌混合,具体比例如下表1所示。
表1不同比例的B2798菌株和幽门螺旋杆菌比例明细
2、短双歧杆菌B2798抑制幽门螺旋杆菌尿素酶活性能力测定
由于幽门螺旋杆菌菌体表面有尿素酶,能分解宿主体内尿素产生氨、中和胃酸,保护菌体免受伤害。尿素酶能够分解尿素提高溶液pH,使指示溶液变色,其活性可以由测定溶液在波长550nm处的吸光度值来反映。
根据麦氏比浊管调节B2798菌株菌悬液和幽门螺旋杆菌菌悬液的活菌数,按照菌株比幽门螺旋杆菌1:1、5:1和10:1的比例在96孔板中,分别吸取40μL幽门螺旋杆菌菌悬液和10μL的B2798菌株菌悬液混匀后,放入三气培养箱中共培养48h,加入150μL尿素酶测试液,震荡后用酶标仪在550nm处测定其吸光值。仅用尿素酶测试液测定的结果作为空白组,使用菌株Pylopass DSM17648代替B2798菌株制备菌悬液测定的结果作为对照组。
所述短双歧杆菌B2798活菌体抑制幽门螺旋杆菌尿素酶活性能力测定结果见下表2所示。
表2短双歧杆菌B2798活菌体抑制幽门螺旋杆菌尿素酶活性能力测定结果
可见,在短双歧杆菌B2798菌株比幽门螺旋杆菌1:1、5:1和10:1的比例条件下,OD550nm值均低于对照组,说明不同浓度的短双歧杆菌B2798菌株均可有效抑制幽门螺旋杆菌的尿素酶活性。
3、待测菌株抑制幽门螺旋杆菌生长能力测定
本实施例利用牛津杯法进行抑菌实验,测定抑菌圈直径,初步探究不同比例下短双歧杆菌B2798菌株对幽门螺旋杆菌的生长抑制作用。
取灭菌后的素琼脂,倒入一次性平板,静置30分钟等待凝固,将灭过菌的牛津杯按照适宜间隔放置刚倒的培养基上,幽门螺旋杆菌按照1%的接种量接种于15mL哥伦比亚培养基(含7%无菌绵羊血),充分混匀后倒入平板,使培养基均匀覆盖平板表面无气泡,等待凝固后用镊子将牛津杯取出,按照B2798菌株比幽门螺旋杆菌1:1、5:1和10:1的比例,分别吸取100μL不同活菌数的B2798菌株菌悬液至圆孔中,将平板放置于三气培养箱中37℃静置培养48h,测量抑菌圈(mm)的大小。
所述短双歧杆菌B2798活菌体抑制幽门螺旋杆菌生长能力测定结果见下表3。
表3短双歧杆菌B2798活菌体抑制幽门螺旋杆菌生长能力测定
可见,随着短双歧杆菌B2798菌株浓度的增加,抑菌圈直径也逐渐增大,通过比例为5:1和10:1的抑菌圈直径结果来看,所述短双歧杆菌B2798菌株可有效抑制幽门螺旋杆菌。
实施例3益生菌固体饮料
本实施例所述益生菌固体饮料的原料质量配比为:短双歧杆菌B2798菌粉5份、水果粉30份、低聚果糖18份、聚葡萄糖4.5份、乳糖醇4.5份、抗性糊精30份。
将上述原料按比例配制并过80目筛;将过筛后的所述原料倒入混合机,转速900r/h,混合时间30min,充分混匀;将混匀后的所述原料倒入灌装设备,进行灌装塑封,得到益生菌固体饮料。
本实施例制备的益生菌固体饮料,所述益生菌固体饮料中,益生菌活菌数大于1010CFU/g。
实施例4益生菌固体饮料
本实施例所述益生菌固体饮料的原料质量配比为:短双歧杆菌B2798菌粉4份、水果粉35份、低聚果糖15份、聚葡萄糖5份、乳糖醇4份、抗性糊精35份。
将上述原料按比例配制并过80目筛;将过筛后的所述原料倒入混合机,转速900r/h,混合时间30min,充分混匀;将混匀后的所述原料倒入灌装设备,进行灌装塑封,得到益生菌固体饮料。
本实施例制备的益生菌固体饮料,所述益生菌固体饮料中,益生菌活菌数大于1010CFU/g。
实施例5益生菌固体饮料
本实施例所述益生菌固体饮料的原料质量配比为:短双歧杆菌B2798菌粉6份、水果粉25份、低聚果糖20份、聚葡萄糖4份、乳糖醇5份、抗性糊精25份。
将上述原料按比例配制并过80目筛;将过筛后的所述原料倒入混合机,转速900r/h,混合时间30min,充分混匀;将混匀后的所述原料倒入灌装设备,进行灌装塑封,得到益生菌固体饮料。
本实施例制备的益生菌固体饮料,所述益生菌固体饮料中,益生菌活菌数大于1010CFU/g。
显然,上述实施例仅仅是为清楚地说明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (8)
1.一株短双歧杆菌B2798,其特征在于,其分类命名为短双歧杆菌Bifidobacteriumbreve,已保藏于中国微生物菌种保藏管理委员会普通微生物中心,保藏编号为CGMCCNo.22242,保藏日期为2021年4月27日。
2.权利要求1所述的短双歧杆菌B2798及其灭活菌体用于制备益生菌制剂的用途。
3.一种益生菌制剂,其特征在于,所述益生菌制剂的活性成分包括权利要求1所述的短双歧杆菌B2798的菌体和/或其灭活菌体。
4.根据权利要求3所述的益生菌制剂,其特征在于,所述益生菌制剂为散剂、颗粒剂、丸剂、胶囊剂、片剂、膏剂、液体制剂、凝胶剂或喷雾剂。
5.一种制备权利要求3或4所述益生菌制剂的方法,其特征在于,包括将权利要求1所述的短双歧杆菌B2798进行菌体培养的步骤,以及按照常规工艺、添加常规辅料进行选定剂型加工的步骤。
6.权利要求1所述的短双歧杆菌B2798及其灭活菌体或者权利要求3或4所述益生菌制剂用于制备治疗炎症性肠病的药物的用途。
7.权利要求1所述的短双歧杆菌B2798用于制备抑制幽门螺旋杆菌的药物的用途。
8.一种幽门螺旋杆菌抑制剂,其特征在于,所述抑制剂活性成分包括权利要求1所述的短双歧杆菌B2798的菌体。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211563484.1A CN116731891B (zh) | 2022-12-07 | 2022-12-07 | 一株短双歧杆菌b2798及其制备益生菌制剂的用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211563484.1A CN116731891B (zh) | 2022-12-07 | 2022-12-07 | 一株短双歧杆菌b2798及其制备益生菌制剂的用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116731891A CN116731891A (zh) | 2023-09-12 |
CN116731891B true CN116731891B (zh) | 2024-05-07 |
Family
ID=87913881
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211563484.1A Active CN116731891B (zh) | 2022-12-07 | 2022-12-07 | 一株短双歧杆菌b2798及其制备益生菌制剂的用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116731891B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116948918B (zh) * | 2023-09-18 | 2023-12-19 | 微康益生菌(苏州)股份有限公司 | 一种抗幽门螺杆菌感染的短双歧杆菌及其应用 |
CN117106672B (zh) * | 2023-10-16 | 2024-01-30 | 微康益生菌(苏州)股份有限公司 | 一种改善衰老相关的认知障碍的短双歧杆菌及其应用 |
CN117431190B (zh) * | 2023-12-14 | 2024-03-12 | 深圳未知君生物科技有限公司 | 一株能够缓解自闭症谱系障碍的短双歧杆菌及其应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101314763A (zh) * | 2007-06-01 | 2008-12-03 | 统一企业(中国)投资有限公司 | 具有抗胃肠道致病菌、抗氧化和降血压作用的短双歧杆菌及其用途 |
CN104232545A (zh) * | 2009-03-10 | 2014-12-24 | 海罗公司 | 来自完全以母乳喂养的婴儿粪便的具有益生活性的菌株的分离、鉴定和表征 |
CN106038611A (zh) * | 2016-07-12 | 2016-10-26 | 江南大学 | 短双歧杆菌c11及其用途 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20190298783A1 (en) * | 2018-03-28 | 2019-10-03 | Morinaga Milk Industry Co., Ltd. | Composition for relieving stress, pharmaceutical composition and food and drink composition and method for relieving stress using the composition for relieving stress |
-
2022
- 2022-12-07 CN CN202211563484.1A patent/CN116731891B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101314763A (zh) * | 2007-06-01 | 2008-12-03 | 统一企业(中国)投资有限公司 | 具有抗胃肠道致病菌、抗氧化和降血压作用的短双歧杆菌及其用途 |
CN104232545A (zh) * | 2009-03-10 | 2014-12-24 | 海罗公司 | 来自完全以母乳喂养的婴儿粪便的具有益生活性的菌株的分离、鉴定和表征 |
CN106038611A (zh) * | 2016-07-12 | 2016-10-26 | 江南大学 | 短双歧杆菌c11及其用途 |
Also Published As
Publication number | Publication date |
---|---|
CN116731891A (zh) | 2023-09-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN116731891B (zh) | 一株短双歧杆菌b2798及其制备益生菌制剂的用途 | |
CN111560330B (zh) | 一种具有免疫调节、抗炎和抗宫颈癌作用的干酪乳杆菌及应用 | |
CN116200306B (zh) | 一种鼠李糖乳酪杆菌LRa16及其在制备治疗生殖道感染的药物方面的用途和产品 | |
CN113005067B (zh) | 多功能复合益生菌制剂及其制备方法 | |
CN113832077A (zh) | 鼠李糖乳杆菌及其应用 | |
CN109609420B (zh) | 一种抗幽门螺旋杆菌的益生菌组合物及其制备方法 | |
CN112458020A (zh) | 一种抑制幽门螺杆菌的益生菌组合物及应用 | |
CN114774315B (zh) | 鼠李糖乳杆菌菌株LRa05在制备增强免疫力制品和/或缓解湿疹制品方面的用途 | |
CN116083325B (zh) | 一种改善幽门螺杆菌相关性胃肠疾病的鼠李糖乳杆菌及其应用 | |
WO2018112741A1 (zh) | 一种嗜酸乳杆菌及其培养方法和应用 | |
EP3808357A1 (en) | Composition and uses thereof | |
CN115838676A (zh) | 利用新型植物乳植杆菌菌株中药发酵及应用 | |
CN113943681A (zh) | 一株降低炎症反应且具有缓解便秘作用的长双歧杆菌 | |
CN109983115B (zh) | 一种加氏乳杆菌及其培养方法和应用 | |
CN111281894B (zh) | 加氏乳杆菌在预防和/或治疗代谢性疾病中的用途和组合物 | |
CN108795823B (zh) | 一种改善女性孕产妇肠道菌群的益生菌的培养方法和应用 | |
CN115119940A (zh) | 嗜酸乳杆菌LA85和乳双歧杆菌BLa80在抑制幽门螺旋杆菌上的应用 | |
CN112888448A (zh) | 单形巨单胞菌在预防和/或治疗代谢性疾病中的用途 | |
CN111685255A (zh) | 一种增强免疫功能的益生菌固体饮料及其制备方法 | |
CN112546074B (zh) | 一株能够抑制IL-23、Th17轴相关炎症因子释放的短双歧杆菌及其应用 | |
CN112236154A (zh) | 一种组合物及其应用 | |
CN116083286B (zh) | 一株婴儿双歧杆菌b8762及其制备益生菌制剂的用途 | |
CN113005066A (zh) | 抗过敏、增加免疫力、降血糖、降脂减肥的复合双歧杆菌制剂及其制备方法 | |
CN112961808A (zh) | 一种降脂减肥的乳双岐杆菌制剂及其制备方法 | |
CN116019842B (zh) | 嗜酸乳杆菌la85的抑菌新用途及其在制备缓解eiec腹泻的药物方面的用途 |
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 |